Science.gov

Sample records for activities involving schedule

  1. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  2. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  3. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  4. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  5. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  6. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS... § 745.1 of the Export Administration Regulations (EAR) (15 CFR parts 730 through 774). For specific... International Traffic in Arms Regulations (22 CFR parts 120 through 130) for Schedule 1 chemicals subject to...

  7. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS... § 745.1 of the Export Administration Regulations (EAR) (15 CFR parts 730 through 774). For specific... International Traffic in Arms Regulations (22 CFR parts 120 through 130) for Schedule 1 chemicals subject to...

  8. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS... § 745.1 of the Export Administration Regulations (EAR) (15 CFR parts 730 through 774). For specific... International Traffic in Arms Regulations (22 CFR parts 120 through 130) for Schedule 1 chemicals subject to...

  9. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS... § 745.1 of the Export Administration Regulations (EAR) (15 CFR parts 730 through 774). For specific... International Traffic in Arms Regulations (22 CFR parts 120 through 130) for Schedule 1 chemicals subject to...

  10. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS... § 745.1 of the Export Administration Regulations (EAR) (15 CFR parts 730 through 774). For specific... International Traffic in Arms Regulations (22 CFR parts 120 through 130) for Schedule 1 chemicals subject to...

  11. A planning language for activity scheduling

    NASA Technical Reports Server (NTRS)

    Zoch, David R.; Lavallee, David; Weinstein, Stuart; Tong, G. Michael

    1991-01-01

    Mission planning and scheduling of spacecraft operations are becoming more complex at NASA. Described here are a mission planning process; a robust, flexible planning language for spacecraft and payload operations; and a software scheduling system that generates schedules based on planning language inputs. The mission planning process often involves many people and organizations. Consequently, a planning language is needed to facilitate communication, to provide a standard interface, and to represent flexible requirements. The software scheduling system interprets the planning language and uses the resource, time duration, constraint, and alternative plan flexibilities to resolve scheduling conflicts.

  12. Mission and science activity scheduling language

    NASA Technical Reports Server (NTRS)

    Hull, Larry G.

    1993-01-01

    To support the distributed and complex operational scheduling required for future National Aeronautics and Space Administration (NASA) missions, a formal, textual language, the Scheduling Applications Interface Language (SAIL), has been developed. Increased geographic dispersion of investigators is leading to distributed mission and science activity planning, scheduling, and operations. SAIL is an innovation which supports the effective and efficient communication of scheduling information among physically dispersed applications in distributed scheduling environments. SAIL offers a clear, concise, unambiguous expression of scheduling information in a readable, hardware independent format. The language concept, syntax, and semantics incorporate language features found useful during five years of research and prototyping with scheduling languages in physically distributed environments. SAIL allows concise specification of mission and science activity plans in a format which promotes repetition and reuse.

  13. Automated Scheduling of Science Activities for Titan Encounters by Cassini

    NASA Technical Reports Server (NTRS)

    Ray, Trina L.; Knight, Russel L.; Mohr, Dave

    2014-01-01

    In an effort to demonstrate the efficacy of automated planning and scheduling techniques for large missions, we have adapted ASPEN (Activity Scheduling and Planning Environment) [1] and CLASP (Compressed Large-scale Activity Scheduling and Planning) [2] to the domain of scheduling high-level science goals into conflict-free operations plans for Titan encounters by the Cassini spacecraft.

  14. Picture Activity Schedules and Engagement of Adults with Mental Retardation in a Group Home.

    ERIC Educational Resources Information Center

    Anderson, Michele D.; Sherman, James A.; Sheldon, Jan B.; McAdam, David

    1997-01-01

    A study involving three adults with mental retardation found engagement in typical adult activities was greater when picture schedules were provided. The schedules provided a reminder for the adults and teaching counselors, provided an easy reference to assist them in determining the next activity, and reduced transition time between activities.…

  15. Determining the Impact of Block Scheduling on Leadership Involvement in the FFA

    ERIC Educational Resources Information Center

    Dunigan, Anne H.; Hoover, Tracy S.

    2007-01-01

    Block scheduling was established in response to educational reform measures and is the restructuring of the school day in longer class increments with fewer number of classes per day. The FFA, an intra-curricular component of the agricultural education, provides leadership opportunities and involvement within the classroom setting. This study…

  16. Scheduling game

    SciTech Connect

    Kleck, W

    1982-04-01

    Structuring a schedule - whether by Critical Path Method (CPM) or Precedence Charting System (PCS) - involves estimating the duration of one or more activities and arranging them in the most logical sequence. Given the start date, the completion date is relatively simple to determine. What is then so complicated about the process. It is complicated by the people involved - the people who make the schedules and the people who attempt to follow them. Schedules are an essential part of project management and construction contract administration. Much of the material available pertains to the mechanics of schedules, the types of logic networks, the ways that data can be generated and presented. This paper sheds light on other facets of the subject - the statistical and philosophical fundamentals involved in scheduling.

  17. Focus of attention in an activity-based scheduler

    NASA Technical Reports Server (NTRS)

    Sadeh, Norman; Fox, Mark S.

    1989-01-01

    Earlier research in job shop scheduling has demonstrated the advantages of opportunistically combining order-based and resource-based scheduling techniques. An even more flexible approach is investigated where each activity is considered a decision point by itself. Heuristics to opportunistically select the next decision point on which to focus attention (i.e., variable ordering heuristics) and the next decision to be tried at this point (i.e., value ordering heuristics) are described that probabilistically account for both activity precedence and resource requirement interactions. Preliminary experimental results indicate that the variable ordering heuristic greatly increases search efficiency. While least constraining value ordering heuristics have been advocated in the literature, the experimental results suggest that other value ordering heuristics combined with our variable-ordering heuristic can produce much better schedules without significantly increasing search.

  18. Optimal stimulus scheduling for active estimation of evoked brain networks

    NASA Astrophysics Data System (ADS)

    Kafashan, MohammadMehdi; Ching, ShiNung

    2015-12-01

    Objective. We consider the problem of optimal probing to learn connections in an evoked dynamic network. Such a network, in which each edge measures an input-output relationship between sites in sensor/actuator-space, is relevant to emerging applications in neural mapping and neural connectivity estimation. Approach. We show that the problem of scheduling nodes to a probe (i.e., stimulate) amounts to a problem of optimal sensor scheduling. Main results. By formulating the evoked network in state-space, we show that the solution to the greedy probing strategy has a convenient form and, under certain conditions, is optimal over a finite horizon. We adopt an expectation maximization technique to update the state-space parameters in an online fashion and demonstrate the efficacy of the overall approach in a series of detailed numerical examples. Significance. The proposed method provides a principled means to actively probe time-varying connections in neuronal networks. The overall method can be implemented in real time and is particularly well-suited to applications in stimulation-based cortical mapping in which the underlying network dynamics are changing over time.

  19. HURON (HUman and Robotic Optimization Network) Multi-Agent Temporal Activity Planner/Scheduler

    NASA Technical Reports Server (NTRS)

    Hua, Hook; Mrozinski, Joseph J.; Elfes, Alberto; Adumitroaie, Virgil; Shelton, Kacie E.; Smith, Jeffrey H.; Lincoln, William P.; Weisbin, Charles R.

    2012-01-01

    HURON solves the problem of how to optimize a plan and schedule for assigning multiple agents to a temporal sequence of actions (e.g., science tasks). Developed as a generic planning and scheduling tool, HURON has been used to optimize space mission surface operations. The tool has also been used to analyze lunar architectures for a variety of surface operational scenarios in order to maximize return on investment and productivity. These scenarios include numerous science activities performed by a diverse set of agents: humans, teleoperated rovers, and autonomous rovers. Once given a set of agents, activities, resources, resource constraints, temporal constraints, and de pendencies, HURON computes an optimal schedule that meets a specified goal (e.g., maximum productivity or minimum time), subject to the constraints. HURON performs planning and scheduling optimization as a graph search in state-space with forward progression. Each node in the graph contains a state instance. Starting with the initial node, a graph is automatically constructed with new successive nodes of each new state to explore. The optimization uses a set of pre-conditions and post-conditions to create the children states. The Python language was adopted to not only enable more agile development, but to also allow the domain experts to easily define their optimization models. A graphical user interface was also developed to facilitate real-time search information feedback and interaction by the operator in the search optimization process. The HURON package has many potential uses in the fields of Operations Research and Management Science where this technology applies to many commercial domains requiring optimization to reduce costs. For example, optimizing a fleet of transportation truck routes, aircraft flight scheduling, and other route-planning scenarios involving multiple agent task optimization would all benefit by using HURON.

  20. Parent Involvement in School-Related Activities.

    ERIC Educational Resources Information Center

    National Center for Education Statistics (ED), Washington, DC.

    Noting that some schools have adopted practices or policies that encourage parents to become more involved in their children's school activities and events, this statistical report (based on the National Household Education Survey) details the level and character of parental involvement in school activities. Findings highlighted are: (1) parents…

  1. Using joint activity schedules to promote peer engagement in preschoolers with autism.

    PubMed

    Betz, Alison; Higbee, Thomas S; Reagon, Kara A

    2008-01-01

    We assessed the use of a joint activity schedule to increase peer engagement for preschoolers with autism. We taught 3 dyads of preschoolers with autism to follow joint activity schedules that cued both members of the pair to play a sequence of interactive games together. Results indicated that joint activity schedules increased peer engagement and the number of games completed for all dyads. Schedule following was maintained without additional prompting when activities were resequenced and when new games were introduced for 2 of the 3 dyads. PMID:18595287

  2. Activity Schedules, Computer Technology, and Teaching Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Stromer, Robert; Kimball, Jonathan W.; Kinney, Elisabeth M.; Taylor, Bridget A.

    2006-01-01

    A review of selected literature suggests that integrating multimedia computer supports with activity schedules can be an effective way to teach students to manage their work, play, and skill-building activities independently. Activity schedules originally were a means of promoting independent execution of previously learned responses by using…

  3. Thermal constraints on activity scheduling and habitat choice in baboons.

    PubMed

    Hill, Russell A

    2006-02-01

    The importance of thermoregulation as a constraint on behavior has received comparatively little attention in relation to other ecological factors. Despite this, a number of studies suggested that high temperature may represent an important ecological constraint. This paper examines the impact of temperature on activity scheduling in a troop of chacma baboons (Papio hamadryas ursinus) at De Hoop Nature Reserve, South Africa. Once the daily, seasonal, and individual effects were controlled for, the "perceived environmental temperature" (PET), which accounts for the relative contributions of solar radiation, wind speed, and humidity on shade temperature, was a significant constraint on behavior. With high PET, feeding declines, and there is an increase in grooming and particularly resting behavior. Baboons thus engage in more sedentary behaviors as temperature increases, with significantly higher levels of resting and grooming when temperature exceeds the approximate thermal neutral zone for baboons. Seeking shade is an important behavioral response to thermal stress, and PET was a significant determinant of whether an animal was in shade while engaged in either resting or grooming behavior. Furthermore, the proportion of time spent in shade increased across air temperatures that were below, within, and above the thermal neutral zone for baboons. Finally, since resting and grooming are conducted preferentially in certain habitat types, thermoregulatory considerations also impact on patterns of habitat choice and day-journey routes. This suggests that the thermal environment is an ecological variable that should be given greater consideration in future studies of primate behavior. PMID:16323181

  4. Establishing Derived Textual Control in Activity Schedules with Children with Autism

    ERIC Educational Resources Information Center

    Miguel, Caio F.; Yang, Heejean G.; Finn, Heather E.; Ahearn, William H.

    2009-01-01

    Activity schedules are often used to facilitate task engagement and transition for children with autism. This study evaluated whether conditional discrimination training would serve to transfer the control from activity-schedule pictures to printed words (i.e., derived textual control). Two preschoolers with autism were taught to select pictures…

  5. Promoting Active Involvement in Today's Classrooms

    ERIC Educational Resources Information Center

    Conderman, Greg; Bresnahan, Val; Hedin, Laura

    2011-01-01

    In today's diverse classrooms and age of accountability, teachers need to use efficient, research-based instructional approaches that engage all students, promote interest and variety in learning and teaching, and provide immediate and continuous informal assessment data. This article presents a rationale for using active involvement techniques,…

  6. Use of Activity Schedule to Promote Independent Performance of Individuals with Autism and Other Intellectual Disabilities: A Review

    ERIC Educational Resources Information Center

    Koyama, Takanori; Wang, Hui-Ting

    2011-01-01

    A literature review was conducted on the effectiveness of activity schedules. Twenty three studies that a) were peer-reviewed, b) were experimental, c) implemented activity schedule as a primary intervention, d) incorporated multiple activities, and e) aimed to teach learners to self-manage individual schedules were included in the review. The…

  7. The Use of Linked Activity Schedules to Teach Children with Autism to Play Hide-and-Seek

    ERIC Educational Resources Information Center

    Brodhead, Matthew T.; Higbee, Thomas S.; Pollard, Joy S.; Akers, Jessica S.; Gerencser, Kristina R.

    2014-01-01

    Linked activity schedules were used to establish appropriate game play in children with autism during a game of hide-and-seek. All 6 participants demonstrated acquisition of appropriate play skills in the presence of the activity schedules and maintained responding during subsequent phases. When the schedules were removed, responding decreased to…

  8. Active Solution Space and Search on Job-shop Scheduling Problem

    NASA Astrophysics Data System (ADS)

    Watanabe, Masato; Ida, Kenichi; Gen, Mitsuo

    In this paper we propose a new searching method of Genetic Algorithm for Job-shop scheduling problem (JSP). The coding method that represent job number in order to decide a priority to arrange a job to Gannt Chart (called the ordinal representation with a priority) in JSP, an active schedule is created by using left shift. We define an active solution at first. It is solution which can create an active schedule without using left shift, and set of its defined an active solution space. Next, we propose an algorithm named Genetic Algorithm with active solution space search (GA-asol) which can create an active solution while solution is evaluated, in order to search the active solution space effectively. We applied it for some benchmark problems to compare with other method. The experimental results show good performance.

  9. Incorporating Active Runway Crossings in Airport Departure Scheduling

    NASA Technical Reports Server (NTRS)

    Gupta, Gautam; Malik, Waqar; Jung, Yoon C.

    2010-01-01

    A mixed integer linear program is presented for deterministically scheduling departure and ar rival aircraft at airport runways. This method addresses different schemes of managing the departure queuing area by treating it as first-in-first-out queues or as a simple par king area where any available aircraft can take-off ir respective of its relative sequence with others. In addition, this method explicitly considers separation criteria between successive aircraft and also incorporates an optional prioritization scheme using time windows. Multiple objectives pertaining to throughput and system delay are used independently. Results indicate improvement over a basic first-come-first-serve rule in both system delay and throughput. Minimizing system delay results in small deviations from optimal throughput, whereas minimizing throughput results in large deviations in system delay. Enhancements for computational efficiency are also presented in the form of reformulating certain constraints and defining additional inequalities for better bounds.

  10. Increasing Completion of Classroom Routines through the Use of Picture Activity Schedules

    ERIC Educational Resources Information Center

    Watson, Kamille J.; DiCarlo, Cynthia F.

    2016-01-01

    Teachers spend the first few days of school teaching routines to children that will help transitions in the classroom between different activities. When children have difficulty, they move more slowly and/or require teacher prompting. A picture activity schedule intervention (Breitfelder in Teach Except Child Plus 4(5):2-15, 2008; Bryan and Gast…

  11. Effects of cocaine on locomotor activity and schedule-controlled behaviors of inbred rat strains.

    PubMed

    Witkin, J M; Goldberg, S R

    1990-10-01

    Effects of cocaine on several behaviors considered to be reflective of psychomotor stimulation were compared in F344/CR1BR and NBR/NIH inbred rat strains. Effects of cocaine on locomotor activity were compared with effects on either bar-press or nose-poke responses maintained under a multiple fixed-interval 3-min, timeout 1-min schedule of food presentation. In locomotor activity experiments, NBR rats were twice as active as F344 rats under baseline conditions and displayed dose-dependent increases in locomotion (5-20 mg/kg). Maximal increases in locomotor activity of F344 rats were only 200% compared to 1000% in NBR rats. In contrast to locomotor activity, no strain differences in the effects of cocaine were observed under the schedules of food delivery. Bar-pressing under the fixed-interval schedule was increased to a maximum of 150% of control in both rat strains. Nose-poke responding under the fixed-interval schedule was not significantly increased, but timeout rates were increased in both strains. These results suggest that NBR and F344 rats do not differ in general sensitivity to stimulant effects of cocaine but exhibit marked differences in responsivity to cocaine that are dependent upon the behavior studied. Further delineation of the behavioral specificity of strain differences in sensitivity to cocaine should help to identify neurobiological substrates underlying unique biologically determined responses to cocaine. PMID:2080195

  12. A Photo Album of Earth Scheduling Landsat 7 Mission Daily Activities

    NASA Technical Reports Server (NTRS)

    Potter, William; Gasch, John; Bauer, Cynthia

    1998-01-01

    Landsat7 is a member of a new generation of Earth observation satellites. Landsat7 will carry on the mission of the aging Landsat 5 spacecraft by acquiring high resolution, multi-spectral images of the Earth surface for strategic, environmental, commercial, agricultural and civil analysis and research. One of the primary mission goals of Landsat7 is to accumulate and seasonally refresh an archive of global images with full coverage of Earth's landmass, less the central portion of Antarctica. This archive will enable further research into seasonal, annual and long-range trending analysis in such diverse research areas as crop yields, deforestation, population growth, and pollution control, to name just a few. A secondary goal of Landsat7 is to fulfill imaging requests from our international partners in the mission. Landsat7 will transmit raw image data from the spacecraft to 25 ground stations in 20 subscribing countries. Whereas earlier Landsat missions were scheduled manually (as are the majority of current low-orbit satellite missions), the task of manually planning and scheduling Landsat7 mission activities would be overwhelmingly complex when considering the large volume of image requests, the limited resources available, spacecraft instrument limitations, and the limited ground image processing capacity, not to mention avoidance of foul weather systems. The Landsat7 Mission Operation Center (MOC) includes an image scheduler subsystem that is designed to automate the majority of mission planning and scheduling, including selection of the images to be acquired, managing the recording and playback of the images by the spacecraft, scheduling ground station contacts for downlink of images, and generating the spacecraft commands for controlling the imager, recorder, transmitters and antennas. The image scheduler subsystem autonomously generates 90% of the spacecraft commanding with minimal manual intervention. The image scheduler produces a conflict-free schedule

  13. Evaluating Visual Activity Schedules as Evidence-Based Practice for Individuals with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Knight, Victoria; Sartini, Emily; Spriggs, Amy D.

    2015-01-01

    A comprehensive review of the literature was conducted for articles published between 1993 and 2013 to evaluate the quality of the Visual Activity Schedules (VAS) literature using current evidence-based criteria developed by Horner et al. (Except Child 71:165-179, 2005). Authors sought to determine whether VAS can be considered an evidence-based…

  14. Intermittent Metronomic Drug Schedule Is Essential for Activating Antitumor Innate Immunity and Tumor Xenograft Regression12

    PubMed Central

    Chen, Chong-Sheng; Doloff, Joshua C; Waxman, David J

    2014-01-01

    Metronomic chemotherapy using cyclophosphamide (CPA) is widely associated with antiangiogenesis; however, recent studies implicate other immune-based mechanisms, including antitumor innate immunity, which can induce major tumor regression in implanted brain tumor models. This study demonstrates the critical importance of drug schedule: CPA induced a potent antitumor innate immune response and tumor regression when administered intermittently on a 6-day repeating metronomic schedule but not with the same total exposure to activated CPA administered on an every 3-day schedule or using a daily oral regimen that serves as the basis for many clinical trials of metronomic chemotherapy. Notably, the more frequent metronomic CPA schedules abrogated the antitumor innate immune and therapeutic responses. Further, the innate immune response and antitumor activity both displayed an unusually steep dose-response curve and were not accompanied by antiangiogenesis. The strong recruitment of innate immune cells by the 6-day repeating CPA schedule was not sustained, and tumor regression was abolished, by a moderate (25%) reduction in CPA dose. Moreover, an ∼20% increase in CPA dose eliminated the partial tumor regression and weak innate immune cell recruitment seen in a subset of the every 6-day treated tumors. Thus, metronomic drug treatment must be at a sufficiently high dose but also sufficiently well spaced in time to induce strong sustained antitumor immune cell recruitment. Many current clinical metronomic chemotherapeutic protocols employ oral daily low-dose schedules that do not meet these requirements, suggesting that they may benefit from optimization designed to maximize antitumor immune responses. PMID:24563621

  15. Parent's Interests, Current Involvement and Level of Parental Involvement in School Activities.

    ERIC Educational Resources Information Center

    Gbadamosi, Tara; Lin, Huey-Ling

    This study examined what school activities parents were involved in and the relationship between parents' interests and level of participation. Parents completed self-report questionnaires examining activities they were currently involved in and activities they would like to do in their children's classrooms. Out of 208 surveys distributed, 114…

  16. Effects of Activity Schedules on Challenging Behavior Exhibited in Children with Autism Spectrum Disorders: A Systematic Review

    ERIC Educational Resources Information Center

    Lequia, Jenna; Machalicek, Wendy; Rispoli, Mandy J.

    2012-01-01

    We reviewed studies implementing activity schedules to decrease challenging behavior of children with autism spectrum disorders (ASD). Systematic searches of electronic databases, journals, and reference lists identified 18 studies meeting the inclusion criteria. These studies were evaluated in terms of the effectiveness of activity schedules to…

  17. DESIGN CONSIDERATION INVOLVING ACTIVE SEDIMENT CAPS (PRESENTATION)

    EPA Science Inventory

    When contaminated sediments pose unacceptable risks to human health and the environment, management activities such as removal, treatment, or isolation of contaminated sediments may be required. Various capping designs are being considered for isolating contaminated sediment are...

  18. DESIGN CONSIDERATION INVOLVING ACTIVE SEDIMENT CAPS

    EPA Science Inventory

    When contaminated sediments pose unacceptable risks to human health and the environment, management activities such as removal, treatment, or isolation of contaminated sediments may be required. Various capping designs are being considered for isolating contaminated sediment are...

  19. Scheduling Software for Complex Scenarios

    NASA Technical Reports Server (NTRS)

    2006-01-01

    Preparing a vehicle and its payload for a single launch is a complex process that involves thousands of operations. Because the equipment and facilities required to carry out these operations are extremely expensive and limited in number, optimal assignment and efficient use are critically important. Overlapping missions that compete for the same resources, ground rules, safety requirements, and the unique needs of processing vehicles and payloads destined for space impose numerous constraints that, when combined, require advanced scheduling. Traditional scheduling systems use simple algorithms and criteria when selecting activities and assigning resources and times to each activity. Schedules generated by these simple decision rules are, however, frequently far from optimal. To resolve mission-critical scheduling issues and predict possible problem areas, NASA historically relied upon expert human schedulers who used their judgment and experience to determine where things should happen, whether they will happen on time, and whether the requested resources are truly necessary.

  20. An Optimal CDS Construction Algorithm with Activity Scheduling in Ad Hoc Networks.

    PubMed

    Penumalli, Chakradhar; Palanichamy, Yogesh

    2015-01-01

    A new energy efficient optimal Connected Dominating Set (CDS) algorithm with activity scheduling for mobile ad hoc networks (MANETs) is proposed. This algorithm achieves energy efficiency by minimizing the Broadcast Storm Problem [BSP] and at the same time considering the node's remaining energy. The Connected Dominating Set is widely used as a virtual backbone or spine in mobile ad hoc networks [MANETs] or Wireless Sensor Networks [WSN]. The CDS of a graph representing a network has a significant impact on an efficient design of routing protocol in wireless networks. Here the CDS is a distributed algorithm with activity scheduling based on unit disk graph [UDG]. The node's mobility and residual energy (RE) are considered as parameters in the construction of stable optimal energy efficient CDS. The performance is evaluated at various node densities, various transmission ranges, and mobility rates. The theoretical analysis and simulation results of this algorithm are also presented which yield better results. PMID:26221627

  1. An Optimal CDS Construction Algorithm with Activity Scheduling in Ad Hoc Networks

    PubMed Central

    Penumalli, Chakradhar; Palanichamy, Yogesh

    2015-01-01

    A new energy efficient optimal Connected Dominating Set (CDS) algorithm with activity scheduling for mobile ad hoc networks (MANETs) is proposed. This algorithm achieves energy efficiency by minimizing the Broadcast Storm Problem [BSP] and at the same time considering the node's remaining energy. The Connected Dominating Set is widely used as a virtual backbone or spine in mobile ad hoc networks [MANETs] or Wireless Sensor Networks [WSN]. The CDS of a graph representing a network has a significant impact on an efficient design of routing protocol in wireless networks. Here the CDS is a distributed algorithm with activity scheduling based on unit disk graph [UDG]. The node's mobility and residual energy (RE) are considered as parameters in the construction of stable optimal energy efficient CDS. The performance is evaluated at various node densities, various transmission ranges, and mobility rates. The theoretical analysis and simulation results of this algorithm are also presented which yield better results. PMID:26221627

  2. The Director of Physical Activity and Staff Involvement

    ERIC Educational Resources Information Center

    Heidorn, Brent; Centeio, Erin

    2012-01-01

    Faculty and staff involvement in the Comprehensive School Physical Activity Program (CSPAP) begins with the Director of Physical Activity (DPA) motivating them to "buy in" to the need for a CSPAP. The DPA will need to train staff to develop and integrate physical activity throughout the school day, encourage them to be involved in the before- and…

  3. Detailed leak detection test plan and schedule for the Oak Ridge National Laboratory LLLW active tanks

    SciTech Connect

    Douglas, D.G.; Maresca, J.W. Jr. )

    1993-03-01

    This document provides a detailed leak detection test plan and schedule for leak testing many of the tanks that comprise the active portion of the liquid low-level waste (LLLW) system at the Oak Ridge National Laboratory (ORNL). This plan was prepared in response to the requirements of the Federal Facility Agreement (FFA) between the US Department of Energy (DOE) and two other agencies, the US Environmental Protection Agency (EPA) and the Tennessee Department of Environment and Conservation (TDEC).

  4. Endothelin involvement in respiratory centre activity.

    PubMed

    Albertini, M; Lafortuna, C L; Ciminaghi, B; Mazzola, S; Clement, M G

    2001-09-01

    To evaluate the role of endothelin (ET) in respiratory homeostasis we studied the effects of the ET(A) and ET(B) receptor blocking agent bosentan on respiratory mechanics and control in seven anaesthetised spontaneously breathing pigs, for 180 min after single bolus administration (20 mg/kg i.v.). The results show that the block of ET receptors induced a significant increase in compliance and decrease in resistance of the respiratory system, entailing a significant reduction of diaphragmatic electromyographic activity, without affecting the centroid frequency of the power spectrum. Bosentan administration induced a significant increase in tidal volume (V(T)), accompanied by a significant decrease in respiratory frequency, without any significant change in pulmonary ventilation, CO(2) arterial blood gas pressure or pH. Since the relationship between V(T) and inspiratory time remained substantially constant after bosentan administration, the changes in respiratory pattern appear to be the result of an upward shift in inspiratory off-switch threshold. Both inspiratory and expiratory times during occluded breathing were increased by block of ET receptors, suggesting also a central respiratory neuromodulator effect of ET. In conclusion the present results suggest that the block of ET receptors in spontaneously breathing pigs exerts a role on mechanical properties of the respiratory system as well as on peripheral and central mechanisms of breathing control. PMID:11728166

  5. Middle Level Activities To Involve the Invisible Student.

    ERIC Educational Resources Information Center

    Rimmer, Sue; Arico, Jim

    Involvement in student activities has many advantages for the middle level student. Such activities promote achievement, citizenship, and service to the community while developing self-esteem, self-confidence, and social cooperation. This book is intended as a tool for middle level schools to motivate, develop, guide, involve, and provide middle…

  6. Exploring Extension Involvement in Farm to School Program Activities

    ERIC Educational Resources Information Center

    Benson, Matthew C.

    2014-01-01

    The study reported here examined Extension professionals' involvement in farm-to-school program activities. Results of an online survey distributed to eight state Extension systems indicate that on average, Extension professionals are involved with one farm to school program activity, with most supporting school or community garden programs.…

  7. Flexible Scheduling.

    ERIC Educational Resources Information Center

    Davis, Harold S.; Bechard, Joseph E.

    A flexible schedule allows teachers to change group size, group composition, and class length according to the purpose of the lesson. This pamphlet presents various "master" schedules for flexible scheduling: (1) Simple block schedules, (2) back-to-back schedules, (3) interdisciplinary schedules, (4) school-wide block schedules, (5) open-lab…

  8. Protocols for distributive scheduling

    NASA Technical Reports Server (NTRS)

    Richards, Stephen F.; Fox, Barry

    1993-01-01

    The increasing complexity of space operations and the inclusion of interorganizational and international groups in the planning and control of space missions lead to requirements for greater communication, coordination, and cooperation among mission schedulers. These schedulers must jointly allocate scarce shared resources among the various operational and mission oriented activities while adhering to all constraints. This scheduling environment is complicated by such factors as the presence of varying perspectives and conflicting objectives among the schedulers, the need for different schedulers to work in parallel, and limited communication among schedulers. Smooth interaction among schedulers requires the use of protocols that govern such issues as resource sharing, authority to update the schedule, and communication of updates. This paper addresses the development and characteristics of such protocols and their use in a distributed scheduling environment that incorporates computer-aided scheduling tools. An example problem is drawn from the domain of space shuttle mission planning.

  9. Empirical Evidence or Intuition? An Activity Involving the Scientific Method

    ERIC Educational Resources Information Center

    Overway, Ken

    2007-01-01

    Students need to have basic understanding of scientific method during their introductory science classes and for this purpose an activity was devised which involved a game based on famous Monty Hall game problem. This particular activity allowed students to banish or confirm their intuition based on empirical evidence.

  10. Predicting scheduling success

    NASA Technical Reports Server (NTRS)

    Messing, Fredric

    1993-01-01

    This paper provides an analytical formulation to predict scheduling success for a class of problems frequently referred to as activity scheduling. Space Network communications scheduling is an example of activity scheduling. The principal assumption is that the activity start times are randomly distributed over the available time in the time line. The formulation makes it possible to estimate how much of the demand can be scheduled as a function of the demand, number of resources, activity duration, and activity flexibility. The paper includes computed results for a variety of resource and demand conditions. The results demonstrate that even with highly flexible activities, it is difficult to schedule demand greater than 60 percent of resources without the use of optimization and conflict resolution capabilities in the scheduling system.

  11. Scheduled Daily Mating Induces Circadian Anticipatory Activity Rhythms in the Male Rat

    PubMed Central

    Landry, Glenn J.; Opiol, Hanna; Marchant, Elliott G.; Pavlovski, Ilya; Mear, Rhiannon J.; Hamson, Dwayne K.; Mistlberger, Ralph E.

    2012-01-01

    Daily schedules of limited access to food, palatable high calorie snacks, water and salt can induce circadian rhythms of anticipatory locomotor activity in rats and mice. All of these stimuli are rewarding, but whether anticipation can be induced by neural correlates of reward independent of metabolic perturbations associated with manipulations of food and hydration is unclear. Three experiments were conducted to determine whether mating, a non-ingestive behavior that is potently rewarding, can induce circadian anticipatory activity rhythms in male rats provided scheduled daily access to steroid-primed estrous female rats. In Experiment 1, rats anticipated access to estrous females in the mid-light period, but also exhibited post-coital eating and running. In Experiment 2, post-coital eating and running were prevented and only a minority of rats exhibited anticipation. Rats allowed to see and smell estrous females showed no anticipation. In both experiments, all rats exhibited sustained behavioral arousal and multiple mounts and intromissions during every session, but ejaculated only every 2–3 days. In Experiment 3, the rats were given more time with individual females, late at night for 28 days, and then in the midday for 28 days. Ejaculation rates increased and anticipation was robust to night sessions and significant although weaker to day sessions. The anticipation rhythm persisted during 3 days of constant dark without mating. During anticipation of nocturnal mating, the rats exhibited a significant preference for a tube to the mating cage over a tube to a locked cage with mating cage litter. This apparent place preference was absent during anticipation of midday mating, which may reflect a daily rhythm of sexual reward. The results establish mating as a reward stimulus capable of inducing circadian rhythms of anticipatory behavior in the male rat, and reveal a critical role for ejaculation, a modulatory role for time of day, and a potential confound role

  12. Scheduled daily mating induces circadian anticipatory activity rhythms in the male rat.

    PubMed

    Landry, Glenn J; Opiol, Hanna; Marchant, Elliott G; Pavlovski, Ilya; Mear, Rhiannon J; Hamson, Dwayne K; Mistlberger, Ralph E

    2012-01-01

    Daily schedules of limited access to food, palatable high calorie snacks, water and salt can induce circadian rhythms of anticipatory locomotor activity in rats and mice. All of these stimuli are rewarding, but whether anticipation can be induced by neural correlates of reward independent of metabolic perturbations associated with manipulations of food and hydration is unclear. Three experiments were conducted to determine whether mating, a non-ingestive behavior that is potently rewarding, can induce circadian anticipatory activity rhythms in male rats provided scheduled daily access to steroid-primed estrous female rats. In Experiment 1, rats anticipated access to estrous females in the mid-light period, but also exhibited post-coital eating and running. In Experiment 2, post-coital eating and running were prevented and only a minority of rats exhibited anticipation. Rats allowed to see and smell estrous females showed no anticipation. In both experiments, all rats exhibited sustained behavioral arousal and multiple mounts and intromissions during every session, but ejaculated only every 2-3 days. In Experiment 3, the rats were given more time with individual females, late at night for 28 days, and then in the midday for 28 days. Ejaculation rates increased and anticipation was robust to night sessions and significant although weaker to day sessions. The anticipation rhythm persisted during 3 days of constant dark without mating. During anticipation of nocturnal mating, the rats exhibited a significant preference for a tube to the mating cage over a tube to a locked cage with mating cage litter. This apparent place preference was absent during anticipation of midday mating, which may reflect a daily rhythm of sexual reward. The results establish mating as a reward stimulus capable of inducing circadian rhythms of anticipatory behavior in the male rat, and reveal a critical role for ejaculation, a modulatory role for time of day, and a potential confound role for

  13. Caste-specific visual adaptations to distinct daily activity schedules in Australian Myrmecia ants.

    PubMed

    Narendra, Ajay; Reid, Samuel F; Greiner, Birgit; Peters, Richard A; Hemmi, Jan M; Ribi, Willi A; Zeil, Jochen

    2011-04-22

    Animals are active at different times of the day and their activity schedules are shaped by competition, time-limited food resources and predators. Different temporal niches provide different light conditions, which affect the quality of visual information available to animals, in particular for navigation. We analysed caste-specific differences in compound eyes and ocelli in four congeneric sympatric species of Myrmecia ants, with emphasis on within-species adaptive flexibility and daily activity rhythms. Each caste has its own lifestyle: workers are exclusively pedestrian; alate females lead a brief life on the wing before becoming pedestrian; alate males lead a life exclusively on the wing. While workers of the four species range from diurnal, diurnal-crepuscular, crepuscular-nocturnal to nocturnal, the activity times of conspecific alates do not match in all cases. Even within a single species, we found eye area, facet numbers, facet sizes, rhabdom diameters and ocelli size to be tuned to the distinct temporal niche each caste occupies. We discuss these visual adaptations in relation to ambient light levels, visual tasks and mode of locomotion. PMID:20926444

  14. Caste-specific visual adaptations to distinct daily activity schedules in Australian Myrmecia ants

    PubMed Central

    Narendra, Ajay; Reid, Samuel F.; Greiner, Birgit; Peters, Richard A.; Hemmi, Jan M.; Ribi, Willi A.; Zeil, Jochen

    2011-01-01

    Animals are active at different times of the day and their activity schedules are shaped by competition, time-limited food resources and predators. Different temporal niches provide different light conditions, which affect the quality of visual information available to animals, in particular for navigation. We analysed caste-specific differences in compound eyes and ocelli in four congeneric sympatric species of Myrmecia ants, with emphasis on within-species adaptive flexibility and daily activity rhythms. Each caste has its own lifestyle: workers are exclusively pedestrian; alate females lead a brief life on the wing before becoming pedestrian; alate males lead a life exclusively on the wing. While workers of the four species range from diurnal, diurnal-crepuscular, crepuscular-nocturnal to nocturnal, the activity times of conspecific alates do not match in all cases. Even within a single species, we found eye area, facet numbers, facet sizes, rhabdom diameters and ocelli size to be tuned to the distinct temporal niche each caste occupies. We discuss these visual adaptations in relation to ambient light levels, visual tasks and mode of locomotion. PMID:20926444

  15. Adolescent Involvement in Extracurricular Activities: Influences on Leadership Skills

    ERIC Educational Resources Information Center

    Hancock, Donna; Dyk, Patricia Hyjer; Jones, Kenneth

    2012-01-01

    Study examined adolescents' participation in sports, school, and community extracurricular activities to assess the influence of different involvement roles and adult support on leadership skills. The study found that males and females who perceived their adult support more positively had more positive perceptions of their leadership skills.…

  16. Bringing Person-Centeredness and Active Involvement into Reality

    ERIC Educational Resources Information Center

    Torenholt, Rikke; Engelund, Gitte; Willaing, Ingrid

    2015-01-01

    Purpose: The purpose of this paper is to examine the use and applicability of cultural probes--an explorative participatory method to gain insights into a person's life and thoughts--to achieve person-centeredness and active involvement in self-management education for people with chronic illness. Design/methodology/approach: An education toolkit…

  17. Moon Watch: A Parental-Involvement Homework Activity.

    ERIC Educational Resources Information Center

    Rillero, Peter; Gonzalez-Jensen, Margarita; Moy, Tracy

    2000-01-01

    Presents the goals, philosophy, and methods of the SPLASH (Student-Parent Laboratories Achieving Science at Home) program. Describes an at-home, parental-involvement activity called Moon Watch in which students and their parents observe how the phases of the moon and the moon's position in the sky change over a two-week period. (WRM)

  18. Constraint based scheduling for the Goddard Space Flight Center distributed Active Archive Center's data archive and distribution system

    NASA Technical Reports Server (NTRS)

    Short, Nick, Jr.; Bedet, Jean-Jacques; Bodden, Lee; Boddy, Mark; White, Jim; Beane, John

    1994-01-01

    The Goddard Space Flight Center (GSFC) Distributed Active Archive Center (DAAC) has been operational since October 1, 1993. Its mission is to support the Earth Observing System (EOS) by providing rapid access to EOS data and analysis products, and to test Earth Observing System Data and Information System (EOSDIS) design concepts. One of the challenges is to ensure quick and easy retrieval of any data archived within the DAAC's Data Archive and Distributed System (DADS). Over the 15-year life of EOS project, an estimated several Petabytes (10(exp 15)) of data will be permanently stored. Accessing that amount of information is a formidable task that will require innovative approaches. As a precursor of the full EOS system, the GSFC DAAC with a few Terabits of storage, has implemented a prototype of a constraint-based task and resource scheduler to improve the performance of the DADS. This Honeywell Task and Resource Scheduler (HTRS), developed by Honeywell Technology Center in cooperation the Information Science and Technology Branch/935, the Code X Operations Technology Program, and the GSFC DAAC, makes better use of limited resources, prevents backlog of data, provides information about resources bottlenecks and performance characteristics. The prototype which is developed concurrently with the GSFC Version 0 (V0) DADS, models DADS activities such as ingestion and distribution with priority, precedence, resource requirements (disk and network bandwidth) and temporal constraints. HTRS supports schedule updates, insertions, and retrieval of task information via an Application Program Interface (API). The prototype has demonstrated with a few examples, the substantial advantages of using HTRS over scheduling algorithms such as a First In First Out (FIFO) queue. The kernel scheduling engine for HTRS, called Kronos, has been successfully applied to several other domains such as space shuttle mission scheduling, demand flow manufacturing, and avionics communications

  19. The Over-Scheduling Hypothesis Revisited: Intensity of Organized Activity Participation during Adolescence and Young Adult Outcomes

    ERIC Educational Resources Information Center

    Mahoney, Joseph L.; Vest, Andrea E.

    2012-01-01

    Concern exists that youth who spend a lot of time participating in organized out-of-school activities (e.g., sports) are at-risk for poor developmental outcomes. This concern--called the over-scheduling hypothesis--has primarily been assessed in terms of adolescent adjustment. This longitudinal study of a nationally representative sample of 1,115…

  20. 15 CFR 714.3 - Advance declaration requirements for additionally planned production of Schedule 3 chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS § 714.3 Advance... a Schedule 3 chemical above the declaration threshold; (ii) You plan to produce at a plant declared under § 714.1(a)(1)(ii) of the CWCR an additional Schedule 3 chemical above the declaration...

  1. 15 CFR 714.3 - Advance declaration requirements for additionally planned production of Schedule 3 chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS § 714.3 Advance... a Schedule 3 chemical above the declaration threshold; (ii) You plan to produce at a plant declared under § 714.1(a)(1)(ii) of the CWCR an additional Schedule 3 chemical above the declaration...

  2. 15 CFR 714.3 - Advance declaration requirements for additionally planned production of Schedule 3 chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS § 714.3 Advance... a Schedule 3 chemical above the declaration threshold; (ii) You plan to produce at a plant declared under § 714.1(a)(1)(ii) of the CWCR an additional Schedule 3 chemical above the declaration...

  3. 15 CFR 714.3 - Advance declaration requirements for additionally planned production of Schedule 3 chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS § 714.3 Advance... a Schedule 3 chemical above the declaration threshold; (ii) You plan to produce at a plant declared under § 714.1(a)(1)(ii) of the CWCR an additional Schedule 3 chemical above the declaration...

  4. Soil microflora and enzyme activities in rhizosphere of Transgenic Bt cotton hybrid under different intercropping systems and plant protection schedules

    NASA Astrophysics Data System (ADS)

    Biradar, D. P.; Alagawadi, A. R.; Basavanneppa, M. A.; Udikeri, S. S.

    2012-04-01

    Field experiments were conducted over three rainy seasons of 2005-06 to 2007-08 on a Vertisol at Dharwad, Karnataka, India to study the effect of intercropping and plant protection schedules on productivity, soil microflora and enzyme activities in the rhizosphere of transgenic Bt cotton hybrid. The experiment consisted of four intercropping systems namely, Bt cotton + okra, Bt cotton + chilli, Bt cotton + onion + chilli and Bt cotton + redgram with four plant protection schedules (zero protection, protection for Bt cotton, protection for intercrop and protection for both crops). Observations on microbial populations and enzyme activities were recorded at 45, 90, 135 and 185 (at harvest) days after sowing (DAS). Averaged over years, Bt cotton + okra intercropping had significantly higher total productivity than Bt cotton + chilli and Bt cotton + redgram intercropping system and was similar to Bt cotton + chilli + onion intercropping system. With respect to plant protection schedules for bollworms, protection for both cotton and intercrops recorded significantly higher yield than the rest of the treatments. Population of total bacteria, fungi, actinomycetes, P-solubilizers, free-living N2 fixers as well as urease, phosphatase and dehydrogenase enzyme activities increased up to 135 days of crop growth followed by a decline. Among the intercropping systems, Bt cotton + chilli recorded significantly higher population of microorganisms and enzyme activities than other cropping systems. While Bt cotton with okra as intercrop recorded the least population of total bacteria and free-living N2 fixers as well as urease activity. Intercropping with redgram resulted in the least population of actinomycetes, fungi and P-solubilizers, whereas Bt cotton with chilli and onion recorded least activities of dehydrogenase and phosphatase. Among the plant protection schedules, zero protection recorded maximum population of microorganisms and enzyme activities. This was followed by the

  5. Enhanced antitumor activity of low-dose continuous administration schedules of topotecan in prostate cancer

    PubMed Central

    Aljuffali, Ibrahim A; Mock, Jason N; Costyn, Leah J; Nguyen, Ha; Nagy, Tamas; Cummings, Brian S

    2011-01-01

    Purpose The objective of this study was to determine the antitumor effects of alternate dosing schedules of topotecan in prostate cancer. Results A concentration-dependent increase in cytotoxicity was observed in PC-3 and LNCaP cells after topotecan treatment using conventional and metronomic protocols. A significant increase in potency (2.4–18 fold, after 72 h) was observed following metronomic dosing compared with conventional dosing administration in both cell lines. Metronomic dosing also increased the percentage of PC-3 cells in the G2/M, compared with control, but did not alter LNCaP cell cycle distribution. Metronomic dosing increased p21 protein expression in LNCaP and PC-3 cells compared with conventional dosing. The observed in vitro activity was confirmed using an in vivo model of human prostate cancer. Metronomic dosing and continuous infusion decreased tumor volume significantly (p ≤ 0.05) compared with control and conventional topotecan treatment, but had no effect on tumor vascular staining. Methods The cytotoxicity of topotecan after conventional or metronomic dosing was determined by examining cellular morphology, mitochondrial enzymatic activity (MTT), total cellular protein (SRB), annexin V and propidium iodine (PI) staining, cell cycle and protein gel blot analysis in human prostate cancer cell lines (PC-3 and LNCaP) and the effects metronomic or continuous infusion on tumor growth in an in vivo tumor xenograft model. Conclusions These data support the hypothesis that low-dose continuous administration of topotecan increases potency compared with conventional dosing in prostate cancer. These data also suggest the novel finding that the enhanced antitumor activity of topotecan following low-dose exposure correlates to alterations in cell cycle and increased p21 expression. PMID:21709443

  6. Sulforaphane Bioavailability and Chemopreventive Activity in Women Scheduled for Breast Biopsy.

    PubMed

    Atwell, Lauren L; Zhang, Zhenzhen; Mori, Motomi; Farris, Paige E; Vetto, John T; Naik, Arpana M; Oh, Karen Y; Thuillier, Philippe; Ho, Emily; Shannon, Jackilen

    2015-12-01

    Epidemiologic studies suggest a protective effect of cruciferous vegetables on breast cancer. Sulforaphane (SFN), an active food component derived from crucifers, has been shown to be effective in breast cancer chemoprevention. This study evaluated the chemopreventive effect of SFN on selective biomarkers from blood and breast tissues. In a 2- to 8-week double-blinded, randomized controlled trial, 54 women with abnormal mammograms and scheduled for breast biopsy were randomized to consume a placebo or a glucoraphanin (GFN) supplement providing SFN (n = 27). Plasma and urinary SFN metabolites, peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity, and tissue biomarkers (H3K18ac, H3K9ac, HDAC3, HDAC6, Ki-67, p21) were measured before and after the intervention in benign, ductal carcinoma in situ, or invasive ductal carcinoma breast tissues. Within the supplement group, Ki-67 (P = 0.003) and HDAC3 (P = 0.044) levels significantly decreased in benign tissue. Pre-to-postintervention changes in these biomarkers were not significantly different between treatment groups after multiple comparison adjustment. GFN supplementation was associated with a significant decrease in PBMC HDAC activity (P = 0.04). No significant associations were observed between SFN and examined tissue biomarkers when comparing treatment groups. This study provides evidence that GFN supplementation for a few weeks is safe but may not be sufficient for producing changes in breast tissue tumor biomarkers. Future studies employing larger sample sizes should evaluate alternative dosing and duration regimens to inform dietary SFN strategies in breast cancer chemoprevention. PMID:26511489

  7. Bipedality and hair loss in human evolution revisited: The impact of altitude and activity scheduling.

    PubMed

    Dávid-Barrett, Tamás; Dunbar, Robin I M

    2016-05-01

    Bipedality evolved early in hominin evolution, and at some point was associated with hair loss over most of the body. One classic explanation (Wheeler 1984: J. Hum. Evol. 13, 91-98) was that these traits evolved to reduce heat overload when australopiths were foraging in more open tropical habitats where they were exposed to the direct effects of sunlight at midday. A recent critique of this model (Ruxton & Wilkinson 2011a: Proc. Natl. Acad. Sci. USA 108, 20965-20969) argued that it ignored the endogenous costs of heat generated by locomotion, and concluded that only hair loss provided a significant reduction in heat load. We add two crucial corrections to this model (the altitude at which australopiths actually lived and activity scheduling) and show that when these are included there are substantial reductions in heat load for bipedal locomotion even for furred animals. In addition, we add one further consideration to the model: we extend the analysis across the full 24 h day, and show that fur loss could not have evolved until much later because of the thermoregulatory costs this would have incurred at the altitudes where australopiths actually lived. Fur loss is most likely associated with the exploitation of open habitats at much lower altitudes at a much later date by the genus Homo. PMID:27178459

  8. 32 CFR 644.8 - Planning and scheduling real estate activities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Project Planning Civil Works § 644.8 Planning and scheduling.... (2) It is essential that adequate funds be programmed on ENG Form 2213, Advance Engineering...

  9. 32 CFR 644.8 - Planning and scheduling real estate activities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Project Planning Civil Works § 644.8 Planning and scheduling.... (2) It is essential that adequate funds be programmed on ENG Form 2213, Advance Engineering...

  10. 32 CFR 644.8 - Planning and scheduling real estate activities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Project Planning Civil Works § 644.8 Planning and scheduling.... (2) It is essential that adequate funds be programmed on ENG Form 2213, Advance Engineering...

  11. 32 CFR 644.8 - Planning and scheduling real estate activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Project Planning Civil Works § 644.8 Planning and scheduling.... (2) It is essential that adequate funds be programmed on ENG Form 2213, Advance Engineering...

  12. 32 CFR 644.8 - Planning and scheduling real estate activities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Project Planning Civil Works § 644.8 Planning and scheduling.... (2) It is essential that adequate funds be programmed on ENG Form 2213, Advance Engineering...

  13. Engaging in activities involving information technology: dimensions, modes, and flow.

    PubMed

    Montgomery, Henry; Sharafi, Parvaneh; Hedman, Leif R

    2004-01-01

    An engagement mode involves a subject (e.g., a user of information technology, or IT) who is engaged in an activity with an object in a certain manner (the mode). The purpose of this study is to develop a general model of engagement modes that may be used for understanding how IT-related activities are shaped by properties of the user and the IT object. A questionnaire involving items on IT engagement and the experience of flow was administered to 300 participants. The results supported an engagement mode (EM) model involving 5 different engagement modes (enjoying/acceptance, ambition/curiosity, avoidance/hesitation, frustration/ anxiety, and efficiency/productivity) characterized on 3 dimensions (evaluation of object, locus of control between subject and object, and intrinsic or extrinsic focus of motivation). The flow experience follows from a balance between enjoying/ acceptance and efficiency/productivity propelled by ambition/curiosity. The EM model could provide a platform for considering how IT users, IT applications, and IT environments should work together to yield both enjoyment and efficiency. Actual or potential applications of this research include designing IT training programs on different levels of specificity. PMID:15359681

  14. Descriptive Study of Activities Identified by Principals as Parental Involvement Activities through Survey Research

    ERIC Educational Resources Information Center

    Anderson, Melinda

    2009-01-01

    This study was designed to identify parental involvement activities used by successful schools. Participating schools were identified as successful by an Academic Excellence Indicator System (AEIS) rating of recognized or exemplary. Using survey methods, data was collected from the principals of the schools about parental involvement activities on…

  15. 15 CFR Supplement No. 2 to Part 712 - Deadlines for Submission of Schedule 1 Declarations, Advance Notifications, Reports, and Amendments

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE...

  16. Diurnal pituitary-adrenal activity during schedule-induced polydipsia of water and ethanol in cynomolgus monkeys (Macaca fascicularis)

    PubMed Central

    Helms, Christa M.; Gonzales, Steven W.; Green, Heather L.; Szeliga, Kendall T.; Rogers, Laura S.M.; Grant, Kathleen A.

    2013-01-01

    Rationale Intermittent delivery of an important commodity (e.g., food pellets) generates excessive behaviors as an adjunct to the schedule of reinforcement (adjunctive behaviors) that are hypothesized to be due to conflict between engaging and escaping a situation where reinforcement is delivered, but at sub-optimal rates. Objectives This study characterized the endocrine correlates during schedule-induced polydipsia (SIP) of water and ethanol using a longitudinal approach in non-human primates. Methods Plasma adrenocorticotropic hormone (ACTH) and cortisol were measured in samples from awake cynomolgus monkeys (Macaca fascicularis, 11 adult males) obtained at the onset, midday and offset of their 12-h light cycle. The monkeys were induced to drink water and ethanol (4% w/v, in water) using a fixed time (FT) 300-s interval schedule of pellet delivery. The induction fluid changed every 30 sessions in the following order: water, 0.5 g/kg ethanol, 1.0 g/kg ethanol, and 1.5 g/kg ethanol. Following induction, ethanol and water were concurrently available for 22 h/d. Results The FT300-s schedule gradually increased ACTH, but not cortisol, during water induction to a plateau sustained throughout ethanol induction in every monkey. Upon termination of the schedule, ACTH decreased to baseline and cortisol below baseline. Diurnal ACTH and cortisol were unrelated to the dose of ethanol, but ACTH rhythm flattened at 0.5 g/kg/d and remained flattened. Conclusions The coincidence of elevated ACTH with the initial experience of drinking to intoxication may have altered the mechanisms involved in the transition to heavy drinking. PMID:23508555

  17. NASA scheduling technologies

    NASA Technical Reports Server (NTRS)

    Adair, Jerry R.

    1994-01-01

    This paper is a consolidated report on ten major planning and scheduling systems that have been developed by the National Aeronautics and Space Administration (NASA). A description of each system, its components, and how it could be potentially used in private industry is provided in this paper. The planning and scheduling technology represented by the systems ranges from activity based scheduling employing artificial intelligence (AI) techniques to constraint based, iterative repair scheduling. The space related application domains in which the systems have been deployed vary from Space Shuttle monitoring during launch countdown to long term Hubble Space Telescope (HST) scheduling. This paper also describes any correlation that may exist between the work done on different planning and scheduling systems. Finally, this paper documents the lessons learned from the work and research performed in planning and scheduling technology and describes the areas where future work will be conducted.

  18. Overwintering strategy of Yunnan snub-nosed monkeys: adjustments in activity scheduling and foraging patterns.

    PubMed

    Grueter, Cyril C; Li, Dayong; Ren, Baoping; Li, Ming

    2013-04-01

    Temperate forests are characterized by pronounced climatic and phenological seasonality. Primates inhabiting such environments experience prolonged resource scarcity and low ambient temperatures in winter and are expected to adjust time allocation and foraging behavior so as to maintain their energy balance. We analyzed the activity scheduling of a group of Yunnan snub-nosed monkeys (Rhinopithecus bieti) based on data collected over 20 months in the high-altitude (>3000 m) Samage Forest, Baimaxueshan Nature Reserve, PRC. The forest consists of evergreen conifers and oaks and deciduous broadleaf trees. The diet varied seasonally, with young leaves preferentially exploited in spring and fruits in summer. The monkeys subsisted on readily available fallback resources (mainly lichens) in winter [Grueter et al. in (Am J Phys Anthropol 140:700-715, 2009)]. We predicted that this switch to a relatively low-quality diet would prompt an increase in feeding effort and decrease in moving effort. We found that the monkeys spent significantly more time feeding in winter than in the other seasons. The monthly time devoted to feeding was also negatively correlated with temperature and positively with percentage of lichens in the diet. Time spent on moving did not vary among seasons or with temperature, but day-journey length was found to be longer on hotter days. Time spent resting was lower in winter and under colder conditions and was also negatively correlated with time spent feeding, indicating that resting time is converted into feeding time during times of ecological stress. These results indicate a strong effect of seasonality on time allocation patterns, constraints on inactivity phases, and the prevalence of an energy-conserving foraging strategy in winter, when costs of thermoregulation were high and the availability of preferred food was low. PMID:23160943

  19. DSN Scheduling Engine

    NASA Technical Reports Server (NTRS)

    Clement, Bradley; Johnston, Mark; Wax, Allan; Chouinard, Caroline

    2008-01-01

    The DSN (Deep Space Network) Scheduling Engine targets all space missions that use DSN services. It allows clients to issue scheduling, conflict identification, conflict resolution, and status requests in XML over a Java Message Service interface. The scheduling requests may include new requirements that represent a set of tracks to be scheduled under some constraints. This program uses a heuristic local search to schedule a variety of schedule requirements, and is being infused into the Service Scheduling Assembly, a mixed-initiative scheduling application. The engine resolves conflicting schedules of resource allocation according to a range of existing and possible requirement specifications, including optional antennas; start of track and track duration ranges; periodic tracks; locks on track start, duration, and allocated antenna; MSPA (multiple spacecraft per aperture); arraying/VLBI (very long baseline interferometry)/delta DOR (differential one-way ranging); continuous tracks; segmented tracks; gap-to-track ratio; and override or block-out of requirements. The scheduling models now include conflict identification for SOA(start of activity), BOT (beginning of track), RFI (radio frequency interference), and equipment constraints. This software will search through all possible allocations while providing a best-effort solution at any time. The engine reschedules to accommodate individual emergency tracks in 0.2 second, and emergency antenna downtime in 0.2 second. The software handles doubling of one mission's track requests over one week (to 42 total) in 2.7 seconds. Further tests will be performed in the context of actual schedules.

  20. Gain-Scheduled Approximations to H-Infinity Controllers for the F/A-18 Active Aeroelastic Wing

    NASA Technical Reports Server (NTRS)

    Lind, Rick

    1999-01-01

    The Active Aeroelastic Wing will demonstrate technologies related to aeroservoelastic effects such as wing twist and load minimization. This paper presents a control design based on H-infinity synthesis that simultaneously considers the multiple objectives associated with handling qualities, actuator limitations, and loads. The controller is realized as a filter and gain set approximation to a state-space H-infinity controller. This approximation allows scheduling of the controller over a flight envelope.

  1. Investing in International Information Exchange Activities to Improve the Safety, Cost Effectiveness and Schedule of Cleanup - 13281

    SciTech Connect

    Seed, Ian; James, Paula; Mathieson, John; Judd, Laurie; Elmetti-Ramirez, Rosa; Han, Ana

    2013-07-01

    With decreasing budgets and increasing pressure on completing cleanup missions as quickly, safely and cost-effectively as possible, there is significant benefit to be gained from collaboration and joint efforts between organizations facing similar issues. With this in mind, the US Department of Energy (DOE) and the UK Nuclear Decommissioning Authority (NDA) have formally agreed to share information on lessons learned on the development and application of new technologies and approaches to improve the safety, cost effectiveness and schedule of the cleanup legacy wastes. To facilitate information exchange a range of tools and methodologies were established. These included tacit knowledge exchange through facilitated meetings, conference calls and Site visits as well as explicit knowledge exchange through document sharing and newsletters. A DOE web-based portal has been established to capture these exchanges and add to them via discussion boards. The information exchange is operating at the Government-to-Government strategic level as well as at the Site Contractor level to address both technical and managerial topic areas. This effort has resulted in opening a dialogue and building working relationships. In some areas joint programs of work have been initiated thus saving resource and enabling the parties to leverage off one another activities. The potential benefits of high quality information exchange are significant, ranging from cost avoidance through identification of an approach to a problem that has been proven elsewhere to cost sharing and joint development of a new technology to address a common problem. The benefits in outcomes significantly outweigh the costs of the process. The applicability of the tools and methods along with the lessons learned regarding some key issues is of use to any organization that wants to improve value for money. In the waste management marketplace, there are a multitude of challenges being addressed by multiple organizations and

  2. Scheduling language and algorithm development study. Appendix: Study approach and activity summary

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The approach and organization of the study to develop a high level computer programming language and a program library are presented. The algorithm and problem modeling analyses are summarized. The approach used to identify and specify the capabilities required in the basic language is described. Results of the analyses used to define specifications for the scheduling module library are presented.

  3. Pontine respiratory activity involved in inspiratory/expiratory phase transition

    PubMed Central

    Mörschel, Michael; Dutschmann, Mathias

    2009-01-01

    Control of the timing of the inspiratory/expiratory (IE) phase transition is a hallmark of respiratory pattern formation. In principle, sensory feedback from pulmonary stretch receptors (Breuer–Hering reflex, BHR) is seen as the major controller for the IE phase transition, while pontine-based control of IE phase transition by both the pontine Kölliker–Fuse nucleus (KF) and parabrachial complex is seen as a secondary or backup mechanism. However, previous studies have shown that the BHR can habituate in vivo. Thus, habituation reduces sensory feedback, so the role of the pons, and specifically the KF, for IE phase transition may increase dramatically. Pontine-mediated control of the IE phase transition is not completely understood. In the present review, we discuss existing models for ponto-medullary interaction that may be involved in the control of inspiratory duration and IE transition. We also present intracellular recordings of pontine respiratory units derived from an in situ intra-arterially perfused brainstem preparation of rats. With the absence of lung inflation, this preparation generates a normal respiratory pattern and many of the recorded pontine units demonstrated phasic respiratory-related activity. The analysis of changes in membrane potentials of pontine respiratory neurons has allowed us to propose a number of pontine-medullary interactions not considered before. The involvement of these putative interactions in pontine-mediated control of IE phase transitions is discussed. PMID:19651653

  4. HIPPARCOS satellite: Aeritalia involvement and system test activities and results

    NASA Astrophysics Data System (ADS)

    Strim, B.; Cugno, W.; Morsillo, G.

    In 1989 the European Space Agency is scheduled to launch HIPPARCOS on a 2.5-year mission that will revolutionize the state of astronomy. This is the first satellite to be dedicated to astrometry, a branch of astronomy that deals with the position of celestial objects and their motion in space. With an accuracy impossible to achieve from Earth, HIPPARCOS will make position, trigonometric parallax and proper motion measurements of some 100.000 pre-selected stars. The data will be used to calculate each star's distance and motion, providing astronomers with an unprecedented map of the heavens. In the end, the HIPPARCOS mission is expected to reveal surprisingly new insight into theories of stellar evolution, as well as into the nature of our galaxy and the universe. The program has been awarded to the MESH industrial consortium for definition, development and production. The French firm MATRA (prime contractor) and the AERITALIA SPACE SYSTEMS GROUP (major co-contractor) share program responsibility. AERITALIA is in charge of the spacecraft or "service module". This is the structural platform for the telescope payload and provides all subsystem services including thermal control, data handling, telecommunications, electrical power distribution, power generation, attitude and orbit control, and apogee kick motor. AERITALIA is responsible for the procurement of all spacecraft subsystems for which it directs the activities of a multinational team of subcontractors. In addition, it is in charge of the satellite's final assembly, integration and testing, as well as for the procurement of all ground support equipment for satellite testing. HIPPARCOS stands for HIgh Precision PARallax COllecting Satellite. Its name is also intended to honor the Greek astronomer Hipparchus (190-120 BC) who compiled the first star catalog and who first used trigonometric parallax to calculate the distance to the moon. (Parallax is the apparent shift in a celestial body's position in the sky

  5. Mission Operations Planning and Scheduling System (MOPSS)

    NASA Technical Reports Server (NTRS)

    Wood, Terri; Hempel, Paul

    2011-01-01

    MOPSS is a generic framework that can be configured on the fly to support a wide range of planning and scheduling applications. It is currently used to support seven missions at Goddard Space Flight Center (GSFC) in roles that include science planning, mission planning, and real-time control. Prior to MOPSS, each spacecraft project built its own planning and scheduling capability to plan satellite activities and communications and to create the commands to be uplinked to the spacecraft. This approach required creating a data repository for storing planning and scheduling information, building user interfaces to display data, generating needed scheduling algorithms, and implementing customized external interfaces. Complex scheduling problems that involved reacting to multiple variable situations were analyzed manually. Operators then used the results to add commands to the schedule. Each architecture was unique to specific satellite requirements. MOPSS is an expert system that automates mission operations and frees the flight operations team to concentrate on critical activities. It is easily reconfigured by the flight operations team as the mission evolves. The heart of the system is a custom object-oriented data layer mapped onto an Oracle relational database. The combination of these two technologies allows a user or system engineer to capture any type of scheduling or planning data in the system's generic data storage via a GUI.

  6. Involving Community Stakeholders to Increase Park Use and Physical Activity

    PubMed Central

    Marsh, Terry; Mariscal, Mark; Pina-Cortez, Sophia; Cohen, Deborah A.

    2014-01-01

    Objective To describe implementation of a randomized controlled trial of community-based participatory research (CBPR) approaches to increase park use and physical activity across 33 diverse neighborhoods in Los Angeles. Methods Fifty parks were randomly assigned based on park size, facilities and programs, and neighborhood socio-demographic characteristics to: park director (PD, 17 parks); PD and park advisory board of interested community members (PD+PAB, 16 parks); and no-intervention control (17 parks) arms. Between 2007 and 2012, PDs and PABs from the 33 intervention parks participated in community engagement, baseline assessment, marketing training, intervention design and implementation, and follow-up assessment. Results Intervention parks (PD and PD+PAB) invested in new and diversified signage, promotional items, outreach or support for group activities like fitness classes and walking clubs, and various marketing strategies. Scaling up CBPR methods across parks in 33 diverse neighborhoods was challenging. Working with departmental management and established structures for community input (PABs) and park policy (PDs) facilitated implementation and sustainability. Conclusion Scaling up CBPR methods across diverse communities involved tradeoffs. CBPR is useful for tailoring research and enhancing community impact and sustainability, but more work is needed to understand how to conduct multi-site trials across diverse settings using CBPR. PMID:24674853

  7. Study of erodable paint properties involved in antifouling activity.

    PubMed

    Thouvenin, M; Langlois, V; Briandet, R; Langlois, J Y; Guerin, P H; Peron, J J; Haras, D; Vallee-Rehel, K

    2003-06-01

    To produce ecological marine paints, it is necessary to understand the phenomena involved in antifouling activity. Due to the multivariable components which have to be taken into account and due to their analytical intricacy, only studies based on selected properties are conceivable. In this study, four properties have been chosen, viz. erosion, biocide release, roughness and the physicochemical characteristics of the film surface. A principal-component analysis (PCA) of the experimental data has shown that, among the selected properties, only erosion affected antifouling efficiency. A more detailed investigation of erosion by quantifying global hydration and hydrolysis of immersed paints revealed the difficulty in linking the chemical structure of binders to the final erosion properties. Biocide release from paints, quantified by chromatographic methods coupled with UV detection, was inferior to the doses stated by the paint producers. These observations allowed the conceiving of formulations with reduced amounts of active molecules. The development of erodable, biodegradable binders associated with non toxic compounds is a promising way to obtain efficient antifouling paints compatible with existing, preventive systems. PMID:14619286

  8. Potent therapeutic activity of irinotecan (CPT-11) and its schedule dependency in medulloblastoma xenografts in nude mice.

    PubMed

    Vassal, G; Boland, I; Santos, A; Bissery, M C; Terrier-Lacombe, M J; Morizet, J; Sainte-Rose, C; Lellouch-Tubiana, A; Kalifa, C; Gouyette, A

    1997-09-26

    The anti-tumor activity of irinotecan (CPT-11), a DNA-topoisomerase 1 inhibitor, was evaluated in 5 advanced stage subcutaneous medulloblastoma xenografts in nude mice, using different schedules of administration. With a 5-day schedule, the highest i.v. dose tested (40 mg kg-1 day-1) induced complete regressions in all xenografts but 1, and delays in tumor growth always exceeded 30 days. Two xenografts, IGRM11 and IGRM33, were highly sensitive, and animals survived tumor-free beyond 120 days after treatment. CPT-11 clearly retained its anti-tumor activity at a lower dosage (27 mg kg-1 day-1). CPT-11 was significantly more active than cyclophosphamide, thiotepa and etoposide against the 3 xenografts evaluated. To study the schedule dependency of its anti-tumor activity, CPT-11 was given i.v. at the same total doses over the same period (33 days) using either a protracted or a sequential schedule in IGRM34-bearing mice. With a dose of 10 mg kg-1 day-1 given on days 0-4, days 7-11, days 21-25 and days 28-32 (total dose, 200 mg kg-1), 3 of 6 animals were tumor free on day 378. The same total dose given with a sequential schedule, i.e., 20 mg kg-1 day-1 on days 0-4 and days 28-32, failed to induce complete regression. The plasma pharmacokinetics of CPT-11 and SN-38 were studied in IGRM34-bearing animals after a single i.v. dose of 10 and 40 mg kg-1. The plasma clearance rate of CPT-11 was dose dependent. The ratio between the SN-38 and CPT-11 area under the curve in plasma was 0.4-0.65, i.e., significantly higher than that observed in humans at the maximum tolerated dose (0.01-0.05). Conversely, this ratio was 10-fold lower in tumor than in plasma. Clinical development of irinotecan is warranted in pediatric malignancies. PMID:9334824

  9. The range scheduling aid

    NASA Technical Reports Server (NTRS)

    Halbfinger, Eliezer M.; Smith, Barry D.

    1991-01-01

    The Air Force Space Command schedules telemetry, tracking and control activities across the Air Force Satellite Control network. The Range Scheduling Aid (RSA) is a rapid prototype combining a user-friendly, portable, graphical interface with a sophisticated object-oriented database. The RSA has been a rapid prototyping effort whose purpose is to elucidate and define suitable technology for enhancing the performance of the range schedulers. Designing a system to assist schedulers in their task and using their current techniques as well as enhancements enabled by an electronic environment, has created a continuously developing model that will serve as a standard for future range scheduling systems. The RSA system is easy to use, easily ported between platforms, fast, and provides a set of tools for the scheduler that substantially increases his productivity.

  10. 15 CFR Supplement No. 2 to Part 713 - Deadlines for Submission of Schedule 2 Declarations, Reports, and Amendments

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS Pt. 713, Supp. 2... following any calendar year in which the production, processing, or consumption of a Schedule 2 chemical... exports or imports of a Schedule 2 chemical by a plant site, trading company, or other person subject...

  11. 15 CFR Supplement No. 2 to Part 714 - Deadlines for Submission of Schedule 3 Declarations, Reports, and Amendments

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS Pt. 714, Supp. 2... Schedule 3 chemical exceeded the declaration threshold in § 714.1(a)(1)(i) of the CWCR. Annual Report on... year in which exports or imports of a Schedule 3 chemical by a plant site, trading company, or...

  12. 15 CFR Supplement No. 2 to Part 714 - Deadlines for Submission of Schedule 3 Declarations, Reports, and Amendments

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS Pt. 714, Supp. 2... Schedule 3 chemical exceeded the declaration threshold in § 714.1(a)(1)(i) of the CWCR. Annual Report on... year in which exports or imports of a Schedule 3 chemical by a plant site, trading company, or...

  13. 15 CFR Supplement No. 2 to Part 713 - Deadlines for Submission of Schedule 2 Declarations, Reports, and Amendments

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS Pt. 713, Supp. 2... following any calendar year in which the production, processing, or consumption of a Schedule 2 chemical... exports or imports of a Schedule 2 chemical by a plant site, trading company, or other person subject...

  14. 15 CFR Supplement No. 2 to Part 714 - Deadlines for Submission of Schedule 3 Declarations, Reports, and Amendments

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS Pt. 714, Supp. 2... Schedule 3 chemical exceeded the declaration threshold in § 714.1(a)(1)(i) of the CWCR. Annual Report on... year in which exports or imports of a Schedule 3 chemical by a plant site, trading company, or...

  15. 15 CFR Supplement No. 2 to Part 713 - Deadlines for Submission of Schedule 2 Declarations, Reports, and Amendments

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS Pt. 713, Supp. 2... following any calendar year in which the production, processing, or consumption of a Schedule 2 chemical... exports or imports of a Schedule 2 chemical by a plant site, trading company, or other person subject...

  16. Multi-day activity scheduling reactions to planned activities and future events in a dynamic model of activity-travel behavior

    NASA Astrophysics Data System (ADS)

    Nijland, Linda; Arentze, Theo; Timmermans, Harry

    2014-01-01

    Modeling multi-day planning has received scarce attention in activity-based transport demand modeling so far. However, new dynamic activity-based approaches are being developed at the current moment. The frequency and inflexibility of planned activities and events in activity schedules of individuals indicate the importance of incorporating those pre-planned activities in the new generation of dynamic travel demand models. Elaborating and combining previous work on event-driven activity generation, the aim of this paper is to develop and illustrate an extension of a need-based model of activity generation that takes into account possible influences of pre-planned activities and events. This paper describes the theory and shows the results of simulations of the extension. The simulation was conducted for six different activities, and the parameter values used were consistent with an earlier estimation study. The results show that the model works well and that the influences of the parameters are consistent, logical, and have clear interpretations. These findings offer further evidence of face and construct validity to the suggested modeling approach.

  17. Effect of Uncertainty on Deterministic Runway Scheduling

    NASA Technical Reports Server (NTRS)

    Gupta, Gautam; Malik, Waqar; Jung, Yoon C.

    2012-01-01

    Active runway scheduling involves scheduling departures for takeoffs and arrivals for runway crossing subject to numerous constraints. This paper evaluates the effect of uncertainty on a deterministic runway scheduler. The evaluation is done against a first-come- first-serve scheme. In particular, the sequence from a deterministic scheduler is frozen and the times adjusted to satisfy all separation criteria; this approach is tested against FCFS. The comparison is done for both system performance (throughput and system delay) and predictability, and varying levels of congestion are considered. The modeling of uncertainty is done in two ways: as equal uncertainty in availability at the runway as for all aircraft, and as increasing uncertainty for later aircraft. Results indicate that the deterministic approach consistently performs better than first-come-first-serve in both system performance and predictability.

  18. A space station onboard scheduling assistant

    NASA Technical Reports Server (NTRS)

    Brindle, A. F.; Anderson, B. H.

    1988-01-01

    One of the goals for the Space Station is to achieve greater autonomy, and have less reliance on ground commanding than previous space missions. This means that the crew will have to take an active role in scheduling and rescheduling their activities onboard, perhaps working from preliminary schedules generated on the ground. Scheduling is a time intensive task, whether performed manually or automatically, so the best approach to solving onboard scheduling problems may involve crew members working with an interactive software scheduling package. A project is described which investigates a system that uses knowledge based techniques for the rescheduling of experiments within the Materials Technology Laboratory of the Space Station. Particular attention is paid to: (1) methods for rapid response rescheduling to accommodate unplanned changes in resource availability, (2) the nature of the interface to the crew, (3) the representation of the many types of data within the knowledge base, and (4) the possibility of applying rule-based and constraint-based reasoning methods to onboard activity scheduling.

  19. Organized Activity Involvement among Rural Youth: Gender Differences in Associations between Activity Type and Developmental Outcomes

    ERIC Educational Resources Information Center

    Ferris, Kaitlyn A.; Oosterhoff, Benjamin; Metzger, Aaron

    2013-01-01

    The current study examined associations between organized activity involvement, academic achievement, and problem behavior in a sample of youth from a non-agricultural based rural community (M[subscript age] = 15.26, Age range = 11-19 years, N = 456). Analyses examined whether associations varied as a function of adolescent gender and age.…

  20. DSN Resource Scheduling

    NASA Technical Reports Server (NTRS)

    Wang, Yeou-Fang; Baldwin, John

    2007-01-01

    TIGRAS is client-side software, which provides tracking-station equipment planning, allocation, and scheduling services to the DSMS (Deep Space Mission System). TIGRAS provides functions for schedulers to coordinate the DSN (Deep Space Network) antenna usage time and to resolve the resource usage conflicts among tracking passes, antenna calibrations, maintenance, and system testing activities. TIGRAS provides a fully integrated multi-pane graphical user interface for all scheduling operations. This is a great improvement over the legacy VAX VMS command line user interface. TIGRAS has the capability to handle all DSN resource scheduling aspects from long-range to real time. TIGRAS assists NASA mission operations for DSN tracking of station equipment resource request processes from long-range load forecasts (ten years or longer), to midrange, short-range, and real-time (less than one week) emergency tracking plan changes. TIGRAS can be operated by NASA mission operations worldwide to make schedule requests for the DSN station equipment.

  1. 5 CFR 1215.24 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Claims involving criminal activity or... PROCEDURES DEBT MANAGEMENT Claims Collection § 1215.24 Claims involving criminal activity or misconduct. (a) A debtor whose indebtedness involves criminal activity such as fraud, embezzlement, theft, or...

  2. 5 CFR 1215.24 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Claims involving criminal activity or... PROCEDURES DEBT MANAGEMENT Claims Collection § 1215.24 Claims involving criminal activity or misconduct. (a) A debtor whose indebtedness involves criminal activity such as fraud, embezzlement, theft, or...

  3. 5 CFR 1215.24 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Claims involving criminal activity or... PROCEDURES DEBT MANAGEMENT Claims Collection § 1215.24 Claims involving criminal activity or misconduct. (a) A debtor whose indebtedness involves criminal activity such as fraud, embezzlement, theft, or...

  4. 5 CFR 1215.24 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Claims involving criminal activity or... PROCEDURES DEBT MANAGEMENT Claims Collection § 1215.24 Claims involving criminal activity or misconduct. (a) A debtor whose indebtedness involves criminal activity such as fraud, embezzlement, theft, or...

  5. The Effects of the Mars Exploration Rovers (MER) Work Schedule Regime on Locomotor Activity Circadian Rhythms, Sleep and Fatigue

    NASA Technical Reports Server (NTRS)

    DeRoshia, Charles W.; Colletti, Laura C.; Mallis, Melissa M.

    2008-01-01

    This study assessed human adaptation to a Mars sol by evaluating sleep metrics obtained by actigraphy and subjective responses in 22 participants, and circadian rhythmicity in locomotor activity in 9 participants assigned to Mars Exploration Rover (MER) operational work schedules (24.65 hour days) at the Jet Propulsion Laboratory in 2004. During MER operations, increased work shift durations and reduced sleep durations and time in bed were associated with the appearance of pronounced 12-hr (circasemidian) rhythms with reduced activity levels. Sleep duration, workload, and circadian rhythm stability have important implications for adaptability and maintenance of operational performance not only of MER operations personnel but also in space crews exposed to a Mars sol of 24.65 hours during future Mars missions.

  6. Sleep Duration, Schedule and Quality among Urban Chinese Children and Adolescents: Associations with Routine After-School Activities

    PubMed Central

    Jiang, Xiaoxiao; Hardy, Louise L.; Baur, Louise A.; Ding, Ding; Wang, Ling; Shi, Huijing

    2015-01-01

    Background With rapid urbanization accompanied by lifestyle changes, children and adolescents living in metropolitan areas are faced with many time use choices that compete with sleep. This study reports on the sleep hygiene of urban Chinese school students, and investigates the relationship between habitual after-school activities and sleep duration, schedule and quality on a regular school day. Methods Cross-sectional, school-based survey of school children (Grades 4–8) living in Shanghai, China, conducted in 2011. Self-reported data were collected on students’ sleep duration and timing, sleep quality, habitual after-school activities (i.e. homework, leisure-time physical activity, recreational screen time and school commuting time), and potential correlates. Results Mean sleep duration of this sample (mean age: 11.5-years; 48.6% girls) was 9 hours. Nearly 30% of students reported daytime tiredness. On school nights, girls slept less (p<0.001) and went to bed later (p<0.001), a sex difference that was more pronounced in older students. Age by sex interactions were observed for both sleep duration (p=0.005) and bedtime (p=0.002). Prolonged time spent on homework and mobile phone playing was related to shorter sleep duration and later bedtime. Adjusting for all other factors, with each additional hour of mobile phone playing, the odds of daytime tiredness and having difficulty maintaining sleep increased by 30% and 27% among secondary students, respectively. Conclusion There are sex differences in sleep duration, schedule and quality. Habitual activities had small but significant associations with sleep hygiene outcomes especially among secondary school students. Intervention strategies such as limiting children’s use of electronic screen devices after school are implicated. PMID:25611973

  7. Extracurricular Activity Involvement and Adolescent Self-Esteem

    ERIC Educational Resources Information Center

    Kort-Butler, Lisa A.

    2012-01-01

    Structured extracurricular activity participation has been linked to self-esteem and other indicators of positive youth development. This article describes the theoretical basis for this relationship, centering on extracurricular activities as a location for identity development. A summary of the empirical evidence points to the importance of…

  8. Radiation protection in radiologic technology: Apathy versus active involvement

    SciTech Connect

    Franz, K.H.

    1982-11-01

    The lack of active participation in radiation protection is a serious problem in Radiologic Technology today. Underlying the problem is professional apathy. An overview of the historical changes, as well as various recent developments in radiology, accentuate the importance of necessary changes in technologists' attitudes and activities. 22 references.

  9. Involvement of Antilipoarabinomannan Antibodies in Classical Complement Activation in Tuberculosis

    PubMed Central

    Hetland, Geir; Wiker, Harald G.; Høgåsen, Kolbjørn; Hamasur, Beston; Svenson, Stefan B.; Harboe, Morten

    1998-01-01

    We examined alternative and classical complement activation induced by whole bacilli of Mycobacterium bovis BCG and Mycobacterium tuberculosis products. After exposure to BCG, there were higher levels of the terminal complement complex in sera from Indian tuberculosis patients than in sera from healthy controls. The addition of BCG with or without EGTA to these sera indicated that approximately 70 to 85% of the total levels of the terminal complement complex was formed by classical activation. Sera from Indian tuberculosis patients contained more antibody to lipoarabinomannan (LAM) than sera from healthy Indians. Levels of anti-LAM immunoglobulin G2 (IgG2), but not anti-LAM IgM, correlated positively with classical activation induced by BCG in the sera. By flow cytometry, deposition of C3 and terminal complement complex on bacilli incubated with normal human serum was demonstrated. The anticomplement staining was significantly reduced in the presence of EGTA and EDTA. Flow cytometry also revealed the binding of complement to BCG incubated with rabbit anti-LAM and then with factor B-depleted serum. This indicates that classical activation plays a major role in complement activation induced by mycobacteria and that anti-LAM IgG on the bacilli can mediate this response. Classical complement activation may be important for the extent of phagocytosis of M. tuberculosis by mononuclear phagocytes, which may influence the course after infection. PMID:9521145

  10. Mission scheduling

    NASA Technical Reports Server (NTRS)

    Gaspin, Christine

    1989-01-01

    How a neural network can work, compared to a hybrid system based on an operations research and artificial intelligence approach, is investigated through a mission scheduling problem. The characteristic features of each system are discussed.

  11. Utilizing AI in Temporal, Spatial, and Resource Scheduling

    NASA Technical Reports Server (NTRS)

    Stottler, Richard; Kalton, Annaka; Bell, Aaron

    2006-01-01

    Aurora is a software system enabling the rapid, easy solution of complex scheduling problems involving spatial and temporal constraints among operations and scarce resources (such as equipment, workspace, and human experts). Although developed for use in the International Space Station Processing Facility, Aurora is flexible enough that it can be easily customized for application to other scheduling domains and adapted as the requirements change or become more precisely known over time. Aurora s scheduling module utilizes artificial-intelligence (AI) techniques to make scheduling decisions on the basis of domain knowledge, including knowledge of constraints and their relative importance, interdependencies among operations, and possibly frequent changes in governing schedule requirements. Unlike many other scheduling software systems, Aurora focuses on resource requirements and temporal scheduling in combination. For example, Aurora can accommodate a domain requirement to schedule two subsequent operations to locations adjacent to a shared resource. The graphical interface allows the user to quickly visualize the schedule and perform changes reflecting additional knowledge or alterations in the situation. For example, the user might drag the activity corresponding to the start of operations to reflect a late delivery.

  12. Patterns of arm muscle activation involved in octopus reaching movements.

    PubMed

    Gutfreund, Y; Flash, T; Fiorito, G; Hochner, B

    1998-08-01

    The extreme flexibility of the octopus arm allows it to perform many different movements, yet octopuses reach toward a target in a stereotyped manner using a basic invariant motor structure: a bend traveling from the base of the arm toward the tip (Gutfreund et al., 1996a). To study the neuronal control of these movements, arm muscle activation [electromyogram (EMG)] was measured together with the kinematics of reaching movements. The traveling bend is associated with a propagating wave of muscle activation, with maximal muscle activation slightly preceding the traveling bend. Tonic activation was occasionally maintained afterward. Correlation of the EMG signals with the kinematic variables (velocities and accelerations) reveals that a significant part of the kinematic variability can be explained by the level of muscle activation. Furthermore, the EMG level measured during the initial stages of movement predicts the peak velocity attained toward the end of the reaching movement. These results suggest that feed-forward motor commands play an important role in the control of movement velocity and that simple adjustment of the excitation levels at the initial stages of the movement can set the velocity profile of the whole movement. A simple model of octopus arm extension is proposed in which the driving force is set initially and is then decreased in proportion to arm diameter at the bend. The model qualitatively reproduces the typical velocity profiles of octopus reaching movements, suggesting a simple control mechanism for bend propagation in the octopus arm. PMID:9671683

  13. Public involvement in environmental activities: Initiatives and lessons learned

    SciTech Connect

    Gray, R.H.

    1995-12-31

    Efforts to communicate the results of environmental studies and involve the public in environmental decisions have increased nationwide. Outreach efforts at two US Department of Energy sites (i.e., the Hanford Site in southeastern Washington State and the Pantex Plant in the Texas Panhandle) have used a broad spectrum of communications media, including technical articles (open literature and symposium publications, annual and topical reports); information brochures and fact sheets; video productions; interactive exhibits; presentations at scientific, technical, civic, and other public meetings; and proactive interactions with the news media and with local, state, federal, and other agencies. In addition, representatives of local communities now operate offsite environmental monitoring stations and Native Americans are involved in studying cultural resources, fisheries, and other issues at Hanford and a program to obtain environmental samples from neighbor`s property is underway at the Pantex Plant. All major environmental programs, such as the multi-year effort to reconstruct past radiological doses to offsite human populations at Hanford, are now conducted with open public participation.

  14. Activation and Involvement of Ral GTPases in Colorectal Cancer

    PubMed Central

    Martin, Timothy D.; Samuel, Jonathan C.; Routh, Elizabeth D.; Der, Channing J.; Yeh, Jen Jen

    2010-01-01

    Current approaches to block KRAS oncogene function focus on inhibition of K-Ras downstream effector signaling. We evaluated the anti-tumor activity of selumetinib (AZD6244, ARRY-142886), a potent and selective MEK1/2 inhibitor, on a panel of colorectal carcinoma (CRC) cells and found no inhibition of KRAS mutant CRC cell anchorage-independent growth. While AKT activity was elevated in KRAS mutant cells, and PI3K inhibition did impair the growth of MEK inhibitor-insensitive CRC cell lines, concurrent treatment with selumetinib did not provide additional anti-tumor activity. Therefore, we speculated that inhibition of the Ral guanine exchange factor (RalGEF) effector pathway may be a more effective approach for blocking CRC growth. RalGEFs are activators of the related RalA and RalB small GTPases and we found activation of both in CRC cell lines and patient tumors. Interfering RNA stable suppression of RalA expression reduced CRC tumor cell anchorage-independent growth, but surprisingly, stable suppression of RalB greatly enhanced soft agar colony size and formation frequency. Despite their opposing activities, both RalA and RalB regulation of anchorage-independent growth required interaction with RalBP1/RLIP76 and components of the exocyst complex. Interestingly, RalA interaction with the Exo84 but not Sec5 exocyst component was necessary for supporting anchorage-independent growth, whereas RalB interaction with Sec5 but not Exo84 was necessary for inhibition of anchorage-independent growth. We suggest that anti-RalA-selective therapies may provide an effective approach for KRAS mutant CRC. PMID:21199803

  15. Artificial masculinization in tilapia involves androgen receptor activation.

    PubMed

    Golan, Matan; Levavi-Sivan, Berta

    2014-10-01

    Estrogens have a pivotal role in natural female sexual differentiation of tilapia while lack of steroids results in testicular development. Despite the fact that androgens do not participate in natural sex differentiation, synthetic androgens, mainly 17-α-methyltestosterone (MT) are effective in the production of all-male fish in aquaculture. The sex inversion potency of synthetic androgens may arise from their androgenic activity or else as inhibitors of aromatase activity. The current study is an attempt to differentiate between the two alleged activities in order to evaluate their contribution to the sex inversion process and aid the search for novel sex inversion agents. In the present study, MT inhibited aromatase activity, when applied in vitro as did the non-aromatizable androgen dihydrotestosterone (DHT). In comparison, exposure to fadrozole, a specific aromatase inhibitor, was considerably more effective. Androgenic activity of MT was evaluated by exposure of Sciaenochromis fryeri fry to the substance and testing for the appearance of blue color. Flutamide, an androgen antagonist, administered concomitantly with MT, reduced the appearance of the blue color and the sex inversion potency of MT in a dose-dependent manner. In tilapia, administration of MT, fadrozole or DHT resulted in efficient sex inversion while flutamide reduced the sex inversion potency of all three compounds. In the case of MT and DHT the decrease in sex inversion efficiency caused by flutamide is most likely due to the direct blocking of the androgen binding to its cognate receptor. The negative effect of flutamide on the efficiency of the fadrozole treatment may indicate that the masculinizing activity of fadrozole may be attributed to excess, un-aromatized, androgens accumulated in the differentiating gonad. The present study shows that when androgen receptors are blocked, there is a reduction in the efficiency of sex inversion treatments. Our results suggest that in contrast to

  16. The Over-Scheduling Hypothesis Revisited: Intensity of Organized Activity Participation During Adolescence and Young Adult Outcomes.

    PubMed

    Mahoney, Joseph L; Vest, Andrea E

    2012-09-01

    Concern exists that youth who spend a lot of time participating in organized out-of-school activities (e.g., sports) are at-risk for poor developmental outcomes. This concern - called the over-scheduling hypothesis - has primarily been assessed in terms of adolescent adjustment. This longitudinal study of a nationally representative sample of 1,115 youth (ages 12-18) assessed long-term relations between intensity of participation during adolescence and adjustment at young adulthood (ages 18-24). Time diaries measured intensity as hours per week of participation. Results showed that, controlling for demographic factors and baseline adjustment, intensity was a significant predictor of positive outcomes (e.g., psychological flourishing, civic engagement, educational attainment) and unrelated to indicators of problematic adjustment (e.g., psychological distress, substance use, antisocial behavior) at young adulthood. PMID:23066336

  17. Hyperosmotic stress activates Rho: differential involvement in Rho kinase-dependent MLC phosphorylation and NKCC activation.

    PubMed

    Di Ciano-Oliveira, Caterina; Sirokmány, Gábor; Szászi, Katalin; Arthur, William T; Masszi, András; Peterson, Mark; Rotstein, Ori D; Kapus, András

    2003-09-01

    Hyperosmotic stress initiates adaptive responses, including phosphorylation of myosin light chain (MLC) and concomitant activation of Na+-K+-Cl- cotransporter (NKCC). Because the small GTPase Rho is a key regulator of MLC phosphorylation, we investigated 1) whether Rho is activated by hyperosmotic stress, and if so, what the triggering factors are, and 2) whether the Rho/Rho kinase (ROK) pathway is involved in MLC phosphorylation and NKCC activation. Rho activity was measured in tubular epithelial cells by affinity pulldown assay. Hyperosmolarity induced rapid (<1 min) and sustained (>20 min) Rho activation that was proportional to the osmotic concentration and reversed within minutes upon restoration of isotonicity. Both decreased cell volume at constant ionic strength and elevated total ionic strength at constant cell volume were capable of activating Rho. Changes in [Na+] and [K+] at normal total salinity failed to activate Rho, and Cl- depletion did not affect the hyperosmotic response. Thus alterations in cellular volume and ionic strength but not individual ion concentrations seem to be the critical triggering factors. Hyperosmolarity induced mono- and diphosphorylation of MLC, which was abrogated by the Rho-family blocker Clostridium toxin B. ROK inhibitor Y-27632 suppressed MLC phosphorylation under isotonic conditions and prevented its rise over isotonic levels in hypertonically stimulated cells. ML-7 had a smaller inhibitory effect. In contrast, it abolished the hypertonic activation of NKCC, whereas Y-27632 failed to inhibit this response. Thus hyperosmolarity activates Rho, and Rho/ROK pathway contributes to basal and hyperosmotic MLC phosphorylation. However, the hypertonic activation of NKCC is ROK independent, implying that the ROK-dependent component of MLC phosphorylation can be uncoupled from NKCC activation. PMID:12748065

  18. Getting Students Involved: Classroom Activities Which Promote Communication.

    ERIC Educational Resources Information Center

    Freeman, G. Ronald; And Others

    Three essays concerning second language classroom activities that promote learning of communication skills are presented. In "From Manipulation to Communication" (Renate A. Schulz), the importance of establishing minimal communicative objectives for classroom instruction skills is discussed, specifying situations in which students have to…

  19. Involvement of Toso in activation of monocytes, macrophages, and granulocytes.

    PubMed

    Lang, Karl S; Lang, Philipp A; Meryk, Andreas; Pandyra, Aleksandra A; Boucher, Louis-Martin; Pozdeev, Vitaly I; Tusche, Michael W; Göthert, Joachim R; Haight, Jillian; Wakeham, Andrew; You-Ten, Annick J; McIlwain, David R; Merches, Katja; Khairnar, Vishal; Recher, Mike; Nolan, Garry P; Hitoshi, Yasumichi; Funkner, Pauline; Navarini, Alexander A; Verschoor, Admar; Shaabani, Namir; Honke, Nadine; Penn, Linda Z; Ohashi, Pamela S; Häussinger, Dieter; Lee, Kyeong-Hee; Mak, Tak W

    2013-02-12

    Rapid activation of immune responses is necessary for antibacterial defense, but excessive immune activation can result in life-threatening septic shock. Understanding how these processes are balanced may provide novel therapeutic potential in treating inflammatory disease. Fc receptors are crucial for innate immune activation. However, the role of the putative Fc receptor for IgM, known as Toso/Faim3, has to this point been unclear. In this study, we generated Toso-deficient mice and used them to uncover a critical regulatory function of Toso in innate immune activation. Development of innate immune cells was intact in the absence of Toso, but Toso-deficient neutrophils exhibited more reactive oxygen species production and reduced phagocytosis of pathogens compared with controls. Cytokine production was also decreased in Toso(-/-) mice compared with WT animals, rendering them resistant to septic shock induced by lipopolysaccharide. However, Toso(-/-) mice also displayed limited cytokine production after infection with the bacterium Listeria monocytogenes that was correlated with elevated presence of Listeria throughout the body. Accordingly, Toso(-/-) mice succumbed to infections of L. monocytogenes, whereas WT mice successfully eliminated the infection. Taken together, our data reveal Toso to be a unique regulator of innate immune responses during bacterial infection and septic shock. PMID:23359703

  20. Involvement of Toso in activation of monocytes, macrophages, and granulocytes

    PubMed Central

    Lang, Karl S.; Lang, Philipp A.; Meryk, Andreas; Pandyra, Aleksandra A.; Boucher, Louis-Martin; Pozdeev, Vitaly I.; Tusche, Michael W.; Göthert, Joachim R.; Haight, Jillian; Wakeham, Andrew; You-Ten, Annick J.; McIlwain, David R.; Merches, Katja; Khairnar, Vishal; Recher, Mike; Nolan, Garry P.; Hitoshi, Yasumichi; Funkner, Pauline; Navarini, Alexander A.; Verschoor, Admar; Shaabani, Namir; Honke, Nadine; Penn, Linda Z.; Ohashi, Pamela S.; Häussinger, Dieter; Lee, Kyeong-Hee; Mak, Tak W.

    2013-01-01

    Rapid activation of immune responses is necessary for antibacterial defense, but excessive immune activation can result in life-threatening septic shock. Understanding how these processes are balanced may provide novel therapeutic potential in treating inflammatory disease. Fc receptors are crucial for innate immune activation. However, the role of the putative Fc receptor for IgM, known as Toso/Faim3, has to this point been unclear. In this study, we generated Toso-deficient mice and used them to uncover a critical regulatory function of Toso in innate immune activation. Development of innate immune cells was intact in the absence of Toso, but Toso-deficient neutrophils exhibited more reactive oxygen species production and reduced phagocytosis of pathogens compared with controls. Cytokine production was also decreased in Toso−/− mice compared with WT animals, rendering them resistant to septic shock induced by lipopolysaccharide. However, Toso−/− mice also displayed limited cytokine production after infection with the bacterium Listeria monocytogenes that was correlated with elevated presence of Listeria throughout the body. Accordingly, Toso−/− mice succumbed to infections of L. monocytogenes, whereas WT mice successfully eliminated the infection. Taken together, our data reveal Toso to be a unique regulator of innate immune responses during bacterial infection and septic shock. PMID:23359703

  1. BIOLOGICAL ACTIVITY AND POTENTIAL REMEDIATION INVOLVING GEOTEXTILE LANDFILL LEACHATE FILTERS

    EPA Science Inventory

    This paper presents the results of a biological growth study in geotextile filters used in landfill leachate collection systems. fter reviewing the first year's activity, a completely new experimental approach has been taken. sing 100 mm diameter columns for the experimental incu...

  2. 15 CFR Supplement No. 1 to Part 712 - Schedule 1 Chemicals

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Schedule 1 Chemicals No. Supplement No. 1 to Part 712 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS...

  3. The insulin receptor activation process involves localized conformational changes.

    PubMed

    Baron, V; Kaliman, P; Gautier, N; Van Obberghen, E

    1992-11-15

    The molecular process by which insulin binding to the receptor alpha-subunit induces activation of the receptor beta-subunit with ensuing substrate phosphorylation remains unclear. In this study, we aimed at approaching this molecular mechanism of signal transduction and at delineating the cytoplasmic domains implied in this process. To do this, we used antipeptide antibodies to the following sequences of the receptor beta-subunit: (i) positions 962-972 in the juxtamembrane domain, (ii) positions 1247-1261 at the end of the kinase domain, and (iii) positions 1294-1317 and (iv) positions 1309-1326, both in the receptor C terminus. We have previously shown that insulin binding to its receptor induces a conformational change in the beta-subunit C terminus. Here, we demonstrate that receptor autophosphorylation induces an additional conformational change. This process appears to be distinct from the one produced by ligand binding and can be detected in at least three different beta-subunit regions: the juxtamembrane domain, the kinase domain, and the C terminus. Hence, the cytoplasmic part of the receptor beta-subunit appears to undergo an extended conformational change upon autophosphorylation. By contrast, the insulin-induced change does not affect the juxtamembrane domain 962-972 nor the kinase domain 1247-1261 and may be limited to the receptor C terminus. Further, we show that the hormone-dependent conformational change is maintained in a kinase-deficient receptor due to a mutation at lysine 1018. Therefore, during receptor activation, the ligand-induced change could precede ATP binding and receptor autophosphorylation. We propose that insulin binding leads to a transient receptor form that may allow ATP binding and, subsequently, autophosphorylation. The second conformational change could unmask substrate-binding sites and stabilize the receptor in an active conformation. PMID:1331080

  4. Laboratory activities involving transmissible spongiform encephalopathy causing agents

    PubMed Central

    Leunda, Amaya; Van Vaerenbergh, Bernadette; Baldo, Aline; Roels, Stefan; Herman, Philippe

    2013-01-01

    Since the appearance in 1986 of epidemic of bovine spongiform encephalopathy (BSE), a new form of neurological disease in cattle which also affected human beings, many diagnostic and research activities have been performed to develop detection and therapeutic tools. A lot of progress was made in better identifying, understanding and controlling the spread of the disease by appropriate monitoring and control programs in European countries. This paper reviews the recent knowledge on pathogenesis, transmission and persistence outside the host of prion, the causative agent of transmissible spongiform encephalopathies (TSE) in mammals with a particular focus on risk (re)assessment and management of biosafety measures to be implemented in diagnostic and research laboratories in Belgium. Also, in response to the need of an increasing number of European diagnostic laboratories stopping TSE diagnosis due to a decreasing number of TSE cases reported in the last years, decontamination procedures and a protocol for decommissioning TSE diagnostic laboratories is proposed. PMID:24055928

  5. Activity of capryloyl collagenic acid against bacteria involved in acne.

    PubMed

    Fourniat, J; Bourlioux, P

    1989-12-01

    Synopsis Capryloyl collagenic acid (Lipacide C8Co) has similar bacteriostatic activity in vitro to that of benzoyl peroxide towards the bacteria found in acne lesions (Staphylococcus aureus, Staphylococcus epidermidis and Propionibacterium acnes) (MIC between 1 and 4 mg ml(-1) for C8Co, and between 0.5 and 5 mg ml(-1) for benzoyl peroxide). The presence of Emulgine M8 did not affect the bacteriostatic activity of C8Co. A 4% w/v solution of C8Co (incorporating Emulgine M8) fulfilled the criteria for an antiseptic preparation as laid down by the French Pharmacopoeia (10th Edition), and had a spectrum 5 bactericidal activity according to the French Standard AFNOR NF T 72-151. The excellent cutaneous tolerance of capryloyl collagenic acid would indicate that an aqueous solution might be of value for topical treatment of the bacterial component of acne. Résumé Activité antibactérienne de l'acide capryloyl-collagénique vis à vis des bactéries impliquées dans l'etiologie de l'acné L'acide capryloyl-collagénique (Lipacide C8Co) et le peroxyde de benzoyle présentent une activité bactériostatique in-vitroéquivalente vis à vis des espèces bactériennes retrouvées au niveau des lésions acnéiques (Staphylococcus aureus, S. epidermidis et Propionibacterium acnes) (CMI comprise entre 1 et 4 mg ml(-1) pour le lipoaminoacide, et 0,5 et 5 mg ml(-1) pour le peroxyde de benzoyle). La mise en solution aqueuse de l'acide capryloyl-collagénique en présence d'Emulgine M8 ne modifie pas son activité bactériostatique. Une telle solution, à 4% m/V d'acide capryloyl-collagénique et 5% m/V d'Emulgine M8, satisfait à l'essai d'activité des préparations antiseptiques décrit à la Pharmacopée Française (Xème Ed.) (concentration minimale antiseptique: 10% v/V, pour un temps de contact de 5 min à 32 degrees C entre les germes tests et la solution diluée en eau distillée), et posséde une activité bactéricide antiseptique spectre 5 conforme à la norme AFNOR NF T

  6. Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage.

    PubMed

    Cervellati, Carlo; Sticozzi, Claudia; Romani, Arianna; Belmonte, Giuseppe; De Rasmo, Domenico; Signorile, Anna; Cervellati, Franco; Milanese, Chiara; Mastroberardino, Pier Giorgio; Pecorelli, Alessandra; Savelli, Vinno; Forman, Henry J; Hayek, Joussef; Valacchi, Giuseppe

    2015-10-01

    A strong correlation between oxidative stress (OS) and Rett syndrome (RTT), a rare neurodevelopmental disorder affecting females in the 95% of the cases, has been well documented although the source of OS and the effect of a redox imbalance in this pathology has not been yet investigated. Using freshly isolated skin fibroblasts from RTT patients and healthy subjects, we have demonstrated in RTT cells high levels of H2O2 and HNE protein adducts. These findings correlated with the constitutive activation of NADPH-oxidase (NOX) and that was prevented by a NOX inhibitor and iron chelator pre-treatment, showing its direct involvement. In parallel, we demonstrated an increase in mitochondrial oxidant production, altered mitochondrial biogenesis and impaired proteasome activity in RTT samples. Further, we found that the key cellular defensive enzymes: glutathione peroxidase, superoxide dismutase and thioredoxin reductases activities were also significantly lower in RTT. Taken all together, our findings suggest that the systemic OS levels in RTT can be a consequence of both: increased endogenous oxidants as well as altered mitochondrial biogenesis with a decreased activity of defensive enzymes that leads to posttranslational oxidant protein modification and a proteasome activity impairment. PMID:26189585

  7. Anticancer Activity of Metal Complexes: Involvement of Redox Processes

    PubMed Central

    Jungwirth, Ute; Kowol, Christian R.; Keppler, Bernhard K.; Hartinger, Christian G.; Berger, Walter; Heffeter, Petra

    2012-01-01

    Cells require tight regulation of the intracellular redox balance and consequently of reactive oxygen species for proper redox signaling and maintenance of metal (e.g., of iron and copper) homeostasis. In several diseases, including cancer, this balance is disturbed. Therefore, anticancer drugs targeting the redox systems, for example, glutathione and thioredoxin, have entered focus of interest. Anticancer metal complexes (platinum, gold, arsenic, ruthenium, rhodium, copper, vanadium, cobalt, manganese, gadolinium, and molybdenum) have been shown to strongly interact with or even disturb cellular redox homeostasis. In this context, especially the hypothesis of “activation by reduction” as well as the “hard and soft acids and bases” theory with respect to coordination of metal ions to cellular ligands represent important concepts to understand the molecular modes of action of anticancer metal drugs. The aim of this review is to highlight specific interactions of metal-based anticancer drugs with the cellular redox homeostasis and to explain this behavior by considering chemical properties of the respective anticancer metal complexes currently either in (pre)clinical development or in daily clinical routine in oncology. PMID:21275772

  8. 32 CFR Appendix B to Part 169a - Commercial Activities Inventory Report and Five-Year Review Schedule

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Field A8. A10 Enter the last two digits of the fiscal year the function is scheduled for study or next... to provide career progression to a needed military skill level in accordance with paragraph E.2.a(1... Indicates that the Installation commander is not scheduling this CA for cost study under the provisions...

  9. 32 CFR Appendix B to Part 169a - Commercial Activities Inventory Report and Five-Year Review Schedule

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Field A8. A10 Enter the last two digits of the fiscal year the function is scheduled for study or next... to provide career progression to a needed military skill level in accordance with paragraph E.2.a(1... Indicates that the Installation commander is not scheduling this CA for cost study under the provisions...

  10. 15 CFR 712.9 - Deadlines for submission of Schedule 1 declarations, reports, advance notifications, and amendments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.9... notifications, and amendments include: (a) Annual declaration on past activities (Schedule 1 chemical...

  11. 15 CFR 712.9 - Deadlines for submission of Schedule 1 declarations, reports, advance notifications, and amendments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.9... notifications, and amendments include: (a) Annual declaration on past activities (Schedule 1 chemical...

  12. 15 CFR 712.9 - Deadlines for submission of Schedule 1 declarations, reports, advance notifications, and amendments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.9... notifications, and amendments include: (a) Annual declaration on past activities (Schedule 1 chemical...

  13. 15 CFR 712.9 - Deadlines for submission of Schedule 1 declarations, reports, advance notifications, and amendments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.9... notifications, and amendments include: (a) Annual declaration on past activities (Schedule 1 chemical...

  14. Effects of a Photo Activity Schedule Book on Independent Task Changes by Students with Intellectual Disabilities in Community and School Job Sites

    ERIC Educational Resources Information Center

    Carson, Keyla D; Gast, David L.; Ayres, Kevin M.

    2008-01-01

    The purpose of this study was to evaluate the effectiveness of using a photo activity schedule book to increase independent transitioning between vocational tasks inside a school cafeteria and at a community job site. Three students with mild to moderate intellectual disabilities, enrolled in a self-contained classroom in a public high school,…

  15. 16 CFR 1031.5 - Criteria for Commission involvement in voluntary standards activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Criteria for Commission involvement in... COMMISSION GENERAL COMMISSION PARTICIPATION AND COMMISSION EMPLOYEE INVOLVEMENT IN VOLUNTARY STANDARDS ACTIVITIES General Policies § 1031.5 Criteria for Commission involvement in voluntary standards...

  16. 16 CFR 1031.5 - Criteria for Commission involvement in voluntary standards activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Criteria for Commission involvement in... COMMISSION GENERAL COMMISSION PARTICIPATION AND COMMISSION EMPLOYEE INVOLVEMENT IN VOLUNTARY STANDARDS ACTIVITIES General Policies § 1031.5 Criteria for Commission involvement in voluntary standards...

  17. Capturing Unique Dimensions of Youth Organized Activity Involvement: Theoretical and Methodological Considerations

    ERIC Educational Resources Information Center

    Bohnert, Amy; Fredricks, Jennifer; Randall, Edin

    2010-01-01

    Despite increased focus on the effects of organized activities on youth development, there is currently no consensus about the best way to assess various dimensions of involvement. This article explores the complexities of assessing involvement and focuses specifically on the following organized activity dimensions: (a) breadth, (b) intensity, (c)…

  18. Involvement in Extracurricular Activities as Related to Academic Performance, Personality, and Peer Acceptance.

    ERIC Educational Resources Information Center

    Fung, Yee-wang; Wong, Ngai-ying

    1991-01-01

    Reveals findings of a survey of 294 Hong Kong secondary school students. Evaluates relationships among involvement in extracurricular activities, academic performance, personality, and peer acceptance. Concludes that activity involvement is positively related to academic performance, personality, and peer acceptance. Suggests that further research…

  19. Breadth and Intensity: Salient, Separable, and Developmentally Significant Dimensions of Structured Youth Activity Involvement

    ERIC Educational Resources Information Center

    Busseri, Michael A.; Rose-Krasnor, Linda

    2009-01-01

    In recent years, an impressive volume of evidence has accumulated demonstrating that youth involvement in structured, organized activities (e.g. school sports, community clubs) may facilitate positive youth development. We present a theory-based framework for studying structured activity involvement (SAI) as a context for positive youth…

  20. Constraint-based scheduling

    NASA Technical Reports Server (NTRS)

    Zweben, Monte

    1991-01-01

    The GERRY scheduling system developed by NASA Ames with assistance from the Lockheed Space Operations Company, and the Lockheed Artificial Intelligence Center, uses a method called constraint-based iterative repair. Using this technique, one encodes both hard rules and preference criteria into data structures called constraints. GERRY repeatedly attempts to improve schedules by seeking repairs for violated constraints. The system provides a general scheduling framework which is being tested on two NASA applications. The larger of the two is the Space Shuttle Ground Processing problem which entails the scheduling of all the inspection, repair, and maintenance tasks required to prepare the orbiter for flight. The other application involves power allocation for the NASA Ames wind tunnels. Here the system will be used to schedule wind tunnel tests with the goal of minimizing power costs. In this paper, we describe the GERRY system and its application to the Space Shuttle problem. We also speculate as to how the system would be used for manufacturing, transportation, and military problems.

  1. Constraint-based scheduling

    NASA Technical Reports Server (NTRS)

    Zweben, Monte

    1993-01-01

    The GERRY scheduling system developed by NASA Ames with assistance from the Lockheed Space Operations Company, and the Lockheed Artificial Intelligence Center, uses a method called constraint-based iterative repair. Using this technique, one encodes both hard rules and preference criteria into data structures called constraints. GERRY repeatedly attempts to improve schedules by seeking repairs for violated constraints. The system provides a general scheduling framework which is being tested on two NASA applications. The larger of the two is the Space Shuttle Ground Processing problem which entails the scheduling of all the inspection, repair, and maintenance tasks required to prepare the orbiter for flight. The other application involves power allocation for the NASA Ames wind tunnels. Here the system will be used to schedule wind tunnel tests with the goal of minimizing power costs. In this paper, we describe the GERRY system and its application to the Space Shuttle problem. We also speculate as to how the system would be used for manufacturing, transportation, and military problems.

  2. Constraint-based scheduling

    NASA Technical Reports Server (NTRS)

    Zweben, Monte

    1991-01-01

    The GERRY scheduling system developed by NASA Ames with assistance from the Lockheed Space Operations Company, and the Lockheed Artificial Intelligence Center, uses a method called constraint based iterative repair. Using this technique, one encodes both hard rules and preference criteria into data structures called constraints. GERRY repeatedly attempts to improve schedules by seeking repairs for violated constraints. The system provides a general scheduling framework which is being tested on two NASA applications. The larger of the two is the Space Shuttle Ground Processing problem which entails the scheduling of all inspection, repair, and maintenance tasks required to prepare the orbiter for flight. The other application involves power allocations for the NASA Ames wind tunnels. Here the system will be used to schedule wind tunnel tests with the goal of minimizing power costs. In this paper, we describe the GERRY system and its applications to the Space Shuttle problem. We also speculate as to how the system would be used for manufacturing, transportation, and military problems.

  3. 76 FR 76935 - Impact of Implementing the Chemical Weapons Convention (CWC) on Commercial Activities Involving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-09

    ... declarations by certain facilities engaged in the production of ``Schedule 1'' chemicals in excess of 100 grams... facilities producing greater than 100 grams aggregate of ``Schedule 1'' chemicals per calendar year (15...

  4. ASTER Scheduling Prioritization Function

    NASA Technical Reports Server (NTRS)

    Cohen, Ron

    1996-01-01

    ASTER schedules are generated by an automated scheduling system. This scheduler will generate psuedo-optimal schedules based on a priority scheme. This priority scheme is controlled by the Science Team.

  5. How Are Transition-to-Kindergarten Activities Associated with Parent Involvement during Kindergarten?

    ERIC Educational Resources Information Center

    Rathbun, Amy H.; Hausken, Elvira Germino

    This study identified the types of transition activities practiced by kindergarten teachers/schools around the country, the relation of various school characteristics to transition activities, and the relation between transition activities and parent involvement during kindergarten. The study sample was comprised of 2,826 public school and 417…

  6. Group scheduling problems in directional sensor networks

    NASA Astrophysics Data System (ADS)

    Singh, Alok; Rossi, André

    2015-12-01

    This article addresses the problem of scheduling a set of groups of directional sensors arising as a result of applying an exact or a heuristic approach for solving a problem involving directional sensors. The problem seeks a schedule for these groups that minimizes the total energy consumed in switching from one group to the next group in the schedule. In practice, when switching from a group to the next one, active sensors in the new group have to rotate in order to face their working direction. These rotations consume energy, and the problem is to schedule the groups so as to minimize the total amount of energy consumed by all the sensor rotations, knowing the initial angular positions of all the sensors. In this article, it is assumed that energy consumption is proportional to the angular movement for all the sensors. Another problem version is also investigated that seeks to minimize the total time during which the sensor network cannot cover all the targets because active sensors are rotating. Both problems are proved to be ?-hard, and a lower bound for the first problem is presented. A greedy heuristic and a genetic algorithm are also proposed for addressing the problem of minimizing total rotation in the general case. Finally, a local search is also proposed to improve the solutions obtained through a genetic algorithm.

  7. 48 CFR 3452.224-71 - Notice about research activities involving human subjects.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 34 CFR part 97: Notice About Research Activities Involving Human Subjects (MAR 2011) (a) Applicable... more of the categories set forth in 34 CFR 97.101(b)(1)-(6). However, if the research subjects are children, the exemption at 34 CFR 97.101(b)(2) (i.e., research involving the use of educational...

  8. 48 CFR 3452.224-72 - Research activities involving human subjects.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a... establish and maintain procedures for the protection of human subjects. The definitions in 34 CFR 97.102... approved by the IRB. (34 CFR 97.103(f).) No covered research involving human subjects shall be...

  9. 48 CFR 3452.224-72 - Research activities involving human subjects.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a... establish and maintain procedures for the protection of human subjects. The definitions in 34 CFR 97.102... approved by the IRB. (34 CFR 97.103(f).) No covered research involving human subjects shall be...

  10. 48 CFR 3452.224-72 - Research activities involving human subjects.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a... establish and maintain procedures for the protection of human subjects. The definitions in 34 CFR 97.102... approved by the IRB. (34 CFR 97.103(f).) No covered research involving human subjects shall be...

  11. 15 CFR Supplement No. 2 to Part 713 - Deadlines for Submission of Schedule 2 Declarations, Reports, and Amendments

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS Pt. 713, Supp. 2... following any calendar year in which the production, processing, or consumption of a Schedule 2...

  12. 15 CFR Supplement No. 2 to Part 714 - Deadlines for Submission of Schedule 3 Declarations, Reports, and Amendments

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS Pt. 714, Supp. 2... Schedule 3 chemical exceeded the declaration threshold in § 714.1(a)(1)(i) of the CWCR. Annual Report...

  13. Health benefits of serious involvement in leisure activities among older Korean adults.

    PubMed

    Kim, Junhyoung; Yamada, Naoko; Heo, Jinmoo; Han, Areum

    2014-01-01

    The existing literature suggests that serious engagement in leisure activities leads to happiness, life satisfaction, and successful aging among older adults. This qualitative study was used to examine the benefits of serious involvement in leisure activities among older Korean adults who were members of a sports club. Using an analytic data analysis, we identified three main themes associated with the benefits of serious engagement in leisure activities: 1) the experience of psychological benefits, 2) the creation of social support, and 3) the enhancement of physical health. These themes indicate that, through serious involvement in certain physical activities, participants gain various health benefits, which may contribute to successful aging. PMID:25059979

  14. Health benefits of serious involvement in leisure activities among older Korean adults

    PubMed Central

    Kim, Junhyoung; Yamada, Naoko; Heo, Jinmoo; Han, Areum

    2014-01-01

    The existing literature suggests that serious engagement in leisure activities leads to happiness, life satisfaction, and successful aging among older adults. This qualitative study was used to examine the benefits of serious involvement in leisure activities among older Korean adults who were members of a sports club. Using an analytic data analysis, we identified three main themes associated with the benefits of serious engagement in leisure activities: 1) the experience of psychological benefits, 2) the creation of social support, and 3) the enhancement of physical health. These themes indicate that, through serious involvement in certain physical activities, participants gain various health benefits, which may contribute to successful aging. PMID:25059979

  15. Detailed leak detection test plan and schedule for the Oak Ridge National Laboratory LLLW active tanks. Waste Management and Environmental Restoration Programs

    SciTech Connect

    Douglas, D.G.; Maresca, J.W. Jr.

    1993-03-01

    This document provides a detailed leak detection test plan and schedule for leak testing many of the tanks that comprise the active portion of the liquid low-level waste (LLLW) system at the Oak Ridge National Laboratory (ORNL). This plan was prepared in response to the requirements of the Federal Facility Agreement (FFA) between the US Department of Energy (DOE) and two other agencies, the US Environmental Protection Agency (EPA) and the Tennessee Department of Environment and Conservation (TDEC).

  16. Functional Communication Training and Chained Schedules of Reinforcement to Treat Challenging Behavior Maintained by Terminations of Activity Interruptions

    ERIC Educational Resources Information Center

    Falcomata, Terry S.; Roane, Henry S.; Muething, Colin S.; Stephenson, Kasey M.; Ing, Anna D.

    2012-01-01

    In this article, the authors evaluated functional communication training (FCT) and a chained schedule of reinforcement for the treatment of challenging behavior exhibited by two individuals diagnosed with Asperger syndrome and autism, respectively. Following a functional analysis with undifferentiated results, the authors demonstrated that…

  17. 32 CFR Appendix B to Part 169a - Commercial Activities Inventory Report and Five-Year Review Schedule

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Field A8. A10 Enter the last two digits of the fiscal year the function is scheduled for study or next...-shore assignments, or the CA is necessary to provide career progression to a needed military skill level... study under the provisions of congressional authority. Y Indicates that the CA is retained...

  18. Getting Involved: Exploring Latino GBT Volunteerism and Activism in AIDS and LGBT Organizations

    PubMed Central

    Ramirez-Valles, Jesus; Kuhns, Lisa M.; Vázquez, Raquel; Benjamin, Gregory D.

    2014-01-01

    The purpose of this paper is to investigate the community involvement (e.g., volunteerism, activism) of Latino gay and bisexual men and transgender persons (GBT) in two areas: AIDS/GLBT and other general causes. Drawing from volunteering and identity theories, we explore: Who is likely to get involved? What factors affect variation in the levels of involvement? Where do Latino GBT participate and what do they do? Data come from a cross-sectional sample (N=643) of Latino GBT in Chicago and San Francisco. We find high levels of involvement, but primarily focused on AIDS/GLBT. Involvement appears to be driven by income, early involvement, role modeling, and childhood stigmatization of gender nonconformity. PMID:26451081

  19. Novel mechanisms for activated protein C cytoprotective activities involving noncanonical activation of protease-activated receptor 3

    PubMed Central

    Burnier, Laurent

    2013-01-01

    The direct cytoprotective activities of activated protein C (APC) on cells convey therapeutic, relevant, beneficial effects in injury and disease models in vivo and require the endothelial protein C receptor (EPCR) and protease activated receptor 1 (PAR1). Thrombin also activates PAR1, but its effects on cells contrast APC’s cytoprotective effects. To gain insights into mechanisms for these contrasting cellular effects, protease activated receptor 3 (PAR3) activation by APC and thrombin was studied. APC cleaved PAR3 on transfected and endothelial cells in the presence of EPCR. Remarkably, APC cleaved a synthetic PAR3 N-terminal peptide at Arg41, whereas thrombin cleaved at Lys38. On cells, APC failed to cleave R41Q-PAR3, whereas K38Q-PAR3 was still cleaved by APC but not by thrombin. PAR3 tethered-ligand peptides beginning at amino acid 42, but not those beginning at amino acid 39, conveyed endothelial barrier-protective effects. In vivo, the APC-derived PAR3 tethered-ligand peptide, but not the thrombin-derived PAR3 peptide, blunted vascular endothelial growth factor (VEGF)-induced vascular permeability. These data indicate that PAR3 cleavage by APC at Arg41 can initiate distinctive APC-like cytoprotective effects. These novel insights help explain the differentiation of APC’s cytoprotective versus thrombin’s proinflammatory effects on cells and suggest a unique contributory role for PAR3 in the complex mechanisms underlying APC cytoprotective effects. PMID:23788139

  20. 48 CFR 3452.224-71 - Notice about research activities involving human subjects.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 34 CFR part 97: Notice About Research Activities Involving Human Subjects (MAR 2011) (a) Applicable... to develop or contribute to generalizable knowledge.” (34 CFR 97.102(d)). If an activity follows a... the individual, or obtains identifiable private information. (34 CFR 97.102(f)). The definition of...

  1. 48 CFR 3452.224-71 - Notice about research activities involving human subjects.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 34 CFR part 97: Notice About Research Activities Involving Human Subjects (MAR 2011) (a) Applicable... to develop or contribute to generalizable knowledge.” (34 CFR 97.102(d)). If an activity follows a... the individual, or obtains identifiable private information. (34 CFR 97.102(f)). The definition of...

  2. Understanding Threshold Effects of Organized Activity Involvement in Adolescents: Sex and Family Income as Moderators

    ERIC Educational Resources Information Center

    Randall, Edin T.; Bohnert, Amy M.

    2012-01-01

    The current study examined the curvilinear links between involvement in organized activities (OA) and sport activities specifically and various indicators of psychological and social development. Participants included 150 9th and 10th graders (57% females) from an urban, selective-enrollment high school. Eligibility for admission is based on city…

  3. A Study of Lipscomb University Students' Internet Use and Involvement in Extracurricular Activities

    ERIC Educational Resources Information Center

    Smith, Samuel Aarron

    2010-01-01

    The purpose of this study was to analyze Lipscomb University students' Internet use and involvement in extracurricular activities. A survey of students at Lipscomb University was conducted. As confirmed by the data the research was able to determine that the type of extracurricular activity a student participates in most often is related to the…

  4. A Longitudinal Study of Breadth and Intensity of Activity Involvement and the Transition to University

    ERIC Educational Resources Information Center

    Busseri, Michael A.; Rose-Krasnor, Linda; Pancer, S. Mark; Pratt, Michael W.; Adams, Gerald R.; Birnie-Lefcovitch, Shelly; Polivy, Janet; Wintre, Maxine Gallander

    2011-01-01

    We examined prospective relations between activity involvement and successful transitioning to university. A sample of 656 students from 6 Canadian universities completed questionnaires before beginning university and at the end of their first year. Breadth (number of different activity domains) and intensity (mean frequency) of activity…

  5. 48 CFR 3452.224-71 - Notice about research activities involving human subjects.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 34 CFR part 97: Notice About Research Activities Involving Human Subjects (MAR 2011) (a) Applicable... to develop or contribute to generalizable knowledge.” (34 CFR 97.102(d)). If an activity follows a... the individual, or obtains identifiable private information. (34 CFR 97.102(f)). The definition of...

  6. Block Scheduling: Center for School Success Promising Practices Series

    ERIC Educational Resources Information Center

    Imbimbo, Josephine; Gilkes, Alwyn

    2009-01-01

    This publication focuses on block scheduling. Alternative scheduling models--usually called "block scheduling" because they involve blocks of time for student learning--restructure the school day. Schools may adopt block scheduling to create more productive and personal relationships among teachers and students, to design challenging curricula…

  7. Activities involving aeronautical, space science, and technology support for minority institutions

    NASA Technical Reports Server (NTRS)

    1993-01-01

    The Final Report addressed the activities with which the Interracial Council for Business Opportunity (ICBO) was involved over the past 12 months. ICBO was involved in the design and development of a CARES Student Tracking System Software (CARES). Cares is intended to provide an effective means of maintaining relevant current and historical information on NASA-funded students through a range of educational program initiatives. ICBP was extensively involved in the formation of a minority university consortium amd implementation of collaborative research activities by the consortium as part of NASA's Mission to Planet Earth/Earth Observing System. ICBO was involved in the formation of an HBCU/MI Consortium to facilitate technology transfer efforts to the small and minority business community in their respective regions.

  8. Detailed leak detection test plan and schedule for Oak Ridge National Laboratory liquid low-level waste active tanks

    SciTech Connect

    1995-01-01

    This document provides a plan and schedule for leak testing a portion of the Liquid Low-Level Waste (LLLW) system at the Oak Ridge National Laboratory (ORNL), Oak Ridge, Tennessee. It is a concise version of a more general leak testing plan that was prepared in response to the requirements of the Federal Facility Agreement (FFA) for the Oak Ridge Reservation (ORR). This plan includes a schedule for the initial reporting of the leak test results from the various tanks that will be tested. The FFA distinguishes four categories of tank and pipeline systems: new systems (Category A), doubly contained systems (Category B), singly contained systems (Category C), and inactive systems (Category D). The FFA specifically requires leak testing of the Category C systems; there are 14 such tanks addressed in this plan, plus one tank (W-12) that has been temporarily returned to service based on EPA and TDEC concurrence. A schedule for testing these tanks is also included. The plan and schedule also addresses an additional 15 Category B tanks have been demonstrated to meet secondary containment requirements. While these 15 tanks are addressed in this plan for the sake of completeness, they have been removed from the leak testing program based on the design demonstrations that show secondary containment. It is noted that the general plan included 42 tanks. Since that report was issued, 26 of those tanks have passed secondary containment design demonstrations and subsequently have been removed from this leak testing plan. In addition, one tank (LA-104) has been removed from service. Accordingly, this document addresses 15 of the LLLW tanks in the system; plans for testing the pipelines will be described in a separate document.

  9. Addressing Three Common Issues in Research on Youth Activities: An Integrative Approach for Operationalizing and Analyzing Involvement

    ERIC Educational Resources Information Center

    Busseri, Michael A.; Rose-Krasnor, Linda

    2010-01-01

    Youth activity involvement has been operationalized and analyzed using a wide range of approaches. Researchers face the challenges of distinguishing between the effects of involvement versus noninvolvement and intensity of involvement in a particular activity, accounting simultaneously for cumulative effects of involvement, and addressing multiple…

  10. Physiological heart activation by adrenaline involves parallel activation of ATP usage and supply.

    PubMed

    Korzeniewski, Bernard; Deschodt-Arsac, Véronique; Calmettes, Guillaume; Franconi, Jean-Michel; Diolez, Philippe

    2008-07-15

    During low-to-high work transition in adult mammalian heart in vivo the concentrations of free ADP, ATP, PCr (phosphocreatine), P(i) and NADH are essentially constant, in striking contrast with skeletal muscle. The direct activation by calcium ions of ATP usage and feedback activation of ATP production by ADP (and P(i)) alone cannot explain this perfect homoeostasis. A comparison of the response to adrenaline (increase in rate-pressure product and [PCr]) of the intact beating perfused rat heart with the elasticities of the PCr producer and consumer to PCr concentration demonstrated that both the ATP/PCr-producing block and ATP/PCr-consuming block are directly activated to a similar extent during physiological heart activation. Our finding constitutes a direct evidence for the parallel-activation mechanism of the regulation of oxidative phosphorylation in heart postulated previously in a theoretical way. PMID:18377364

  11. Radiosensitizing Properties of Bortezomib Depend on Therapeutic Schedule

    SciTech Connect

    Labussiere, Marianne; Pinel, Sophie; Vandamme, Marc; Plenat, Francois; Chastagner, Pascal

    2011-03-01

    Purpose: To investigate the influence of the bortezomib (BTZ) on malignant glioma radiosensitivity in two xenograft models. Methods and Materials: For TCG3 and U87 models, we evaluated the antitumor activity of BTZ, radiotherapy, and BTZ plus radiothearapy according to two therapeutic schedules: a 'nonfractionated' schedule corresponding to a single dose of treatment per week, and a 'fractionated' schedule corresponding to the same weekly dose divided into 5 fractions. Treatments influence on proliferation and apoptosis indexes, cell cycle distribution, and nuclear factor-{kappa}B pathway were explored. Results: The radiosensitizing properties of BTZ observed with the nonfractionated schedule were lost with the fractionated schedule. Bortezomib-mediated radiosensitization was associated with an increased apoptosis response and major changes in cell proliferation, but the nuclear factor-{kappa}B pathway was not involved. Most of the cellular effects induced by BTZ when tumors received a single irradiation were cancelled out if radiotherapy was fractionated. Conclusion: The influence of BTZ on glioma radiosensitivity seems to depend on the treatment fractionation schedule, emphasizing the need to clarify the mechanisms underlying BTZ's radiosensitizing effects before further clinical trials are initiated.

  12. Scheduling Reconsidered (Again!)

    ERIC Educational Resources Information Center

    Hentschke, Guilbert C.; Fowler, William J.

    1974-01-01

    Computer technicians bring to school scheduling a certain naivete regarding the operation of schools. School administrators play a fundamental role of informing technicians about education scheduling needs. (Author)

  13. Molecular genetic analysis of activation-tagged transcription factors thought to be involved in photomorphogenesis

    SciTech Connect

    Neff, Michael M.

    2011-06-23

    This is a final report for Department of Energy Grant No. DE-FG02-08ER15927 entitled “Molecular Genetic Analysis of Activation-Tagged Transcription Factors Thought to be Involved in Photomorphogenesis”. Based on our preliminary photobiological and genetic analysis of the sob1-D mutant, we hypothesized that OBP3 is a transcription factor involved in both phytochrome and cryptochrome-mediated signal transduction. In addition, we hypothesized that OBP3 is involved in auxin signaling and root development. Based on our preliminary photobiological and genetic analysis of the sob2-D mutant, we also hypothesized that a related gene, LEP, is involved in hormone signaling and seedling development.

  14. Idle Hands and Empty Pockets?: Youth Involvement in Extracurricular Activities, Social Capital, and Economic Status

    ERIC Educational Resources Information Center

    White, Amanda M.; Gager, Constance T.

    2007-01-01

    Using data from the Survey of Adults and Youth, the authors examine the effect of economic status on youths' involvement in both school- and nonschool-related extracurricular activities. Specifically, they assess the association between four alternative measures of economic status--recipiency of food stamps, Aid to Families with Dependent…

  15. Involving Your Child or Teen with ASD in Integrated Community Activities

    ERIC Educational Resources Information Center

    McKee, Rebecca

    2011-01-01

    Participating in outside activities and community-based endeavors can be tricky for people with special needs, like Autism Spectrum Disorder (ASD). Families meet more than a few obstacles attempting to integrate their children or teens who have special needs like ASD. Most typical children are highly involved in sports, clubs and camps. If a…

  16. An Active Self-Determination Technique: Involving Students in Effective Career Planning.

    ERIC Educational Resources Information Center

    Denison, Grace L.

    This paper discusses creating story boards to help students with disabilities to develop effective career plans. It describes storyboarding as a technique for project planning which requires active involvement of both hemispheres of the brain. A group of 6-8 people, including students, teachers, counselors, and vocational rehabilitation…

  17. Beyond Participation: The Association between School Extracurricular Activities and Involvement in Violence across Generations of Immigration

    ERIC Educational Resources Information Center

    Jiang, Xin; Peterson, Ruth D.

    2012-01-01

    Participation in extracurricular activities is purported to protect the broad spectrum of youth from a host of behavioral risks. Yet, empirical research on the extent to which this assumption holds for involvement in violence by immigrant youth is limited. Thus, using data for 13,236 (51.8% female) adolescents from the National Longitudinal Study…

  18. An Emergent Language Program Framework: Actively Involving Learners in Needs Analysis.

    ERIC Educational Resources Information Center

    Savage, William; Storer, Graeme

    1992-01-01

    Relates the experience of the staff of an aquaculture outreach program in Northeast Thailand in implementing an English for special purposes program. By actively involving learners in both the needs analysis and program design, teachers were able to adapt the program content to the requirements of the students. (15 references) (JL)

  19. INVOLVEMENT OF MICRORNAS IN EMBRYONIC GENOME ACTIVATION AS SHOWN BY DICER EXPRESSION IN RAINBOW TROUT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most maternal transcripts including many housekeeping genes are degraded at or around embryonic genome activation as evidenced by our initial studies. This degradation appears to be global but highly regulated. MicroRNAs are naturally occurring small (19-24bp) RNAs that are shown to be involved in m...

  20. Longitudinal Modeling of Adolescents' Activity Involvement, Problem Peer Associations, and Youth Smoking

    ERIC Educational Resources Information Center

    Metzger, Aaron; Dawes, Nickki; Mermelstein, Robin; Wakschlag, Lauren

    2011-01-01

    Longitudinal associations among different types of organized activity involvement, problem peer associations, and cigarette smoking were examined in a sample of 1040 adolescents (mean age = 15.62 at baseline, 16.89 at 15-month assessment, 17.59 at 24 months) enriched for smoking experimentation (83% had tried smoking). A structural equation model…

  1. A Longitudinal Examination of Breadth and Intensity of Youth Activity Involvement and Successful Development

    ERIC Educational Resources Information Center

    Busseri, Michael A.; Rose-Krasnor, Linda; Willoughby, Teena; Chalmers, Heather

    2006-01-01

    Connections between youth activity involvement and indicators of successful development were examined in a longitudinal high school sample. Drawing on theories of expertise skill development (e.g., J. Cote, 1999); the selection, optimization, and compensation framework (P. B. Baltes, 1997); and theories of positive youth development (e.g., R. M.…

  2. 78 FR 57818 - Commission Participation and Commission Employee Involvement in Voluntary Standards Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-20

    ... Commission Employee Involvement in Voluntary Standards Activities. 54 FR 6646 (Feb. 14, 1989). In 2006, the Commission amended several provisions of part 1031. 71 FR 38754 (July 10, 2006). Among other things, the 2006... the development of voluntary standards (43 FR 19216 (May 4, 1978)). Acknowledging the...

  3. 48 CFR 3452.224-72 - Research activities involving human subjects.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Research activities involving human subjects. 3452.224-72 Section 3452.224-72 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses...

  4. 45 CFR 1177.4 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 3 2012-10-01 2012-10-01 false Claims involving criminal activity or misconduct. 1177.4 Section 1177.4 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION §...

  5. 45 CFR 1177.4 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false Claims involving criminal activity or misconduct. 1177.4 Section 1177.4 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION §...

  6. 45 CFR 1177.4 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 false Claims involving criminal activity or misconduct. 1177.4 Section 1177.4 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION §...

  7. 45 CFR 1177.4 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Claims involving criminal activity or misconduct. 1177.4 Section 1177.4 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION §...

  8. 45 CFR 1177.4 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 false Claims involving criminal activity or misconduct. 1177.4 Section 1177.4 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION §...

  9. Involving Parents of Young Children in Science, Math and Literacy Activities.

    ERIC Educational Resources Information Center

    Landerholm, Elizabeth; And Others

    1995-01-01

    Describes a collaborative parent-involvement project for inner-city Hispanic primary students sponsored by the Chicago Community Trust. A university professor, two graduate assistants, the principal, and the school community representative designed a summer program featuring hospitality and support activities, free books, and hands-on science and…

  10. Increasing Student Involvement in Self-Governance Activities: A Delphi Approach.

    ERIC Educational Resources Information Center

    Miles, Jennifer M.; Miller, Michael T.

    This study used a Delphi survey to examine what undergraduate student government leaders think about increasing student involvement in self-governance activities. Twenty-students from geographically diverse institutions of higher education participated in the three rounds of the Delphi study. They generated a total of 56 different strategies and…

  11. Beyond the Classroom: Involving Students with Disabilities in Extracurricular Activities at Levy Middle School.

    ERIC Educational Resources Information Center

    Walker, Pam; And Others

    Six students in a special education classroom at Levy Middle School (Syracuse, New York) became involved in a variety of after-school activities with nondisabled students. The students participated in the school computer club, cross-country skiing, volleyball, stage crew, intramural basketball, the Spanish Club, and after-school programs at two…

  12. NASA launch schedule

    NASA Astrophysics Data System (ADS)

    Bell, Peter M.

    The National Aeronautics and Space Administration (NASA) has a record-setting launch schedule for 1984—10 space shuttle flights (see Table 1), 10 satellite deployments from the space shuttle in orbit and 12 unmanned missions using expendable launch vehicles. Also scheduled is the launch on March 1 for the National Oceanic and Atmospheric Administration of Landsat D‧, the nation's second earth resources satellite.The launch activity will begin February 3 with the launch of shuttle mission 41-B using the orbiter Challenger. Two communications satellites will be deployed from 41-B: Westar-VI, for Western Union, and Palapa B-2 for the government of Indonesia. The 8-day mission will feature the first shuttle landing at Kennedy Space Center in Florida; and the first flight of the Manned Maneuvering Unit, a self-contained, propulsive backpack that will allow astronauts to move about in space without being tethered to the spacecraft.

  13. [Specific activity of an UV-inactivated antirabies vaccine made from brain tissue administered in a shortened schedule].

    PubMed

    Morogova, V M; Magazov, R Sh; Gil'dina, S S; Latypova, R G; Shafeeva, R S

    1982-04-01

    The results obtained in the study of the specific potency of rabies vaccine prepared from sheep brain tissue and inactivated by UV irradiation indicate that, even in the presence of the lowest immunogenicity index (0.5), 5-6 injections of the vaccine, made not daily, but at interval of 3 and 7 days, induced the production of antibodies in the titers not lower than those resulting from 14-20 daily injections of the same vaccine or Fermi vaccine. The preparation inactivated by UV irradiation should be introduced for therapy according to the shortened immunization schedule with intervals, taking into account the immunogenicity index. PMID:7080770

  14. Modification and updating of the Manned Activity Scheduling System (MASS) for shuttle and shuttle payloads analysis. Volume 1: Model specifications

    NASA Technical Reports Server (NTRS)

    Ring, R. C.

    1973-01-01

    The LRC MASS was modified and updated to include logic for efficient analysis of space shuttle payload operations. All MASS computer models were reviewed for compatibility with, and applicability to, the shuttle sortie mission. The MASS modification efforts were concentrated on two computer programs, the general scheduling model (GSM) and one day model (ODM). A new computer program, the DAYLIB Tape Processor, was developed to update the link between the GSM and ODM. The resulting MASS is an operationally efficient analytical tool that will allow a rapid assessment of shuttle and shuttle payload operations.

  15. Future aircraft networks and schedules

    NASA Astrophysics Data System (ADS)

    Shu, Yan

    2011-07-01

    Because of the importance of air transportation scheduling, the emergence of small aircraft and the vision of future fuel-efficient aircraft, this thesis has focused on the study of aircraft scheduling and network design involving multiple types of aircraft and flight services. It develops models and solution algorithms for the schedule design problem and analyzes the computational results. First, based on the current development of small aircraft and on-demand flight services, this thesis expands a business model for integrating on-demand flight services with the traditional scheduled flight services. This thesis proposes a three-step approach to the design of aircraft schedules and networks from scratch under the model. In the first step, both a frequency assignment model for scheduled flights that incorporates a passenger path choice model and a frequency assignment model for on-demand flights that incorporates a passenger mode choice model are created. In the second step, a rough fleet assignment model that determines a set of flight legs, each of which is assigned an aircraft type and a rough departure time is constructed. In the third step, a timetable model that determines an exact departure time for each flight leg is developed. Based on the models proposed in the three steps, this thesis creates schedule design instances that involve almost all the major airports and markets in the United States. The instances of the frequency assignment model created in this thesis are large-scale non-convex mixed-integer programming problems, and this dissertation develops an overall network structure and proposes iterative algorithms for solving these instances. The instances of both the rough fleet assignment model and the timetable model created in this thesis are large-scale mixed-integer programming problems, and this dissertation develops subproblem schemes for solving these instances. Based on these solution algorithms, this dissertation also presents

  16. An investigation on impacts of scheduling configurations on Mississippi biology subject area testing

    NASA Astrophysics Data System (ADS)

    Marchette, Frances Lenora

    The purpose of this mixed modal study was to compare the results of Biology Subject Area mean scores of students on a 4 x 4 block schedule, A/B block schedule, and traditional year-long schedule for 1A to 5A size schools. This study also reviewed the data to determine if minority or gender issues might influence the test results. Interviews with administrators and teachers were conducted about the type of schedule configuration they use and the influence that the schedule has on student academic performance on the Biology Subject Area Test. Additionally, this research further explored whether schedule configurations allow sufficient time for students to construct knowledge. This study is important to schools, teachers, and administrators because it can assist them in considering the impacts that different types of class schedules have on student performance and if ethnic or gender issues are influencing testing results. This study used the causal-comparative method for the quantitative portion of the study and constant comparative method for the qualitative portion to explore the relationship of school schedules on student academic achievement on the Mississippi Biology Subject Area Test. The aggregate means of selected student scores indicate that the Mississippi Biology Subject Area Test as a measure of student performance reveals no significant difference on student achievement for the three school schedule configurations. The data were adjusted for initial differences of gender, minority, and school size on the three schedule configurations. The results suggest that schools may employ various schedule configurations and expect student performance on the Mississippi Biology Subject Area Test to be unaffected. However, many areas of concern were identified in the interviews that might impact on school learning environments. These concerns relate to effective classroom management, the active involvement of students in learning, the adequacy of teacher education

  17. Spent nuclear fuel project integrated schedule plan

    SciTech Connect

    Squires, K.G.

    1995-03-06

    The Spent Nuclear Fuel Integrated Schedule Plan establishes the organizational responsibilities, rules for developing, maintain and status of the SNF integrated schedule, and an implementation plan for the integrated schedule. The mission of the SNFP on the Hanford site is to provide safe, economic, environmentally sound management of Hanford SNF in a manner which stages it to final disposition. This particularly involves K Basin fuel.

  18. Schedule Risk Assessment

    NASA Technical Reports Server (NTRS)

    Smith, Greg

    2003-01-01

    Schedule risk assessments determine the likelihood of finishing on time. Each task in a schedule has a varying degree of probability of being finished on time. A schedule risk assessment quantifies these probabilities by assigning values to each task. This viewgraph presentation contains a flow chart for conducting a schedule risk assessment, and profiles applicable several methods of data analysis.

  19. The Block Scheduling Handbook.

    ERIC Educational Resources Information Center

    Queen, J. Allen

    Block scheduling encourages increased comprehensive immersion into subject matter, improved teacher-student relationships, and decreased disciplinary problems. While block scheduling may offer many advantages, moving to a block schedule from conventional scheduling can be a major adjustment for both students and teachers. This guide is intended to…

  20. Barriers to involvement in physical activities of persons with mental illness.

    PubMed

    Shor, Ron; Shalev, Anat

    2016-03-01

    Participating in physical activities could be essential for reducing the multiple risk factors for health problems that persons with severe mental illness (SMI) may suffer. However, people with SMI are significantly less active than the general population. To develop knowledge about factors related to the perceived barriers hindering this population's participation in physical activities and the benefits this participation would have, a study was conducted in Israel with 86 people with mental illness living in community mental health facilities prior to their participation in a health promotion program. A mixed method was implemented and included: a scale designed to measure participants' perceptions of the barriers to and benefits of involvement in physical activities; instruments focusing on bio-psycho-social factors that may affect the level of barriers experienced; and personal interviews. The findings revealed high ranking for accessibility barriers hindering the participation in physical activities. Bio-psycho-social factors stemming from the participants' mental health, such as level of depression, were correlated with higher ranking of accessibility barriers. Bio-psycho-social factors reflecting positive mental health and health, such as positive appraisal of body weight, were correlated with lower ranking of accessibility barriers. Other barriers may include organizational and broader systemic barriers in the mental health facilities where the participants reside. These findings illuminate the need to consider the unique challenges that persons with mental illness may face in any attempt to advance their involvement in physical activity. PMID:25204451

  1. Scheduling Spitzer: The SIRPASS Story

    NASA Technical Reports Server (NTRS)

    Mittman, David S.; Hawkins, Robert

    2013-01-01

    NASA's Spitzer Space Telescope was launched on August 25, 2003 from Florida's Cape Canaveral Air Force Base. Drifting in a unique Earth-trailing orbit around the Sun, Spitzer sees an optically invisible universe dominated by dust and stars. Since 1997, the Spitzer Integrated Resource Planning and Scheduling System (SIRPASS) has helped produce spacecraft activity plans for the Spitzer Space Telescope. SIRPASS is used by members of the Observatory Planning and Scheduling Team to plan, schedule and sequence the Telescope from data made available to them from the science and engineering community. Because of the volume of data that needs to be scheduled, SIRPASS offers a variety of automated assistants to aid in this task. This paper will describe the functional elements of the SIRPASS software system -- emphasizing the role that automation plays in the system -- and will highlight lessons learned for the software developer from a decade of Spitzer Space Telescope operations experience.

  2. Differential involvement of amygdala and cortical NMDA receptors activation upon encoding in odor fear memory.

    PubMed

    Hegoburu, Chloé; Parrot, Sandrine; Ferreira, Guillaume; Mouly, Anne-Marie

    2014-12-01

    Although the basolateral amygdala (BLA) plays a crucial role for the acquisition of fear memories, sensory cortices are involved in their long-term storage in rats. However, the time course of their respective involvement has received little investigation. Here we assessed the role of the glutamatergic N-methyl-d-aspartate (NMDA) receptors in the BLA and olfactory cortex at discrete moments of an odor fear conditioning session. We showed that NMDA receptors in BLA are critically involved in odor fear acquisition during the first association but not during the next ones. In the cortex, NMDA receptor activation at encoding is not necessary for recent odor fear memory while its role in remote memory storage needs further investigation. PMID:25403452

  3. Supporting Real-Time Operations and Execution through Timeline and Scheduling Aids

    NASA Technical Reports Server (NTRS)

    Marquez, Jessica J.; Pyrzak, Guy; Hashemi, Sam; Ahmed, Samia; McMillin, Kevin Edward; Medwid, Joseph Daniel; Chen, Diana; Hurtle, Esten

    2013-01-01

    Since 2003, the NASA Ames Research Center has been actively involved in researching and advancing the state-of-the-art of planning and scheduling tools for NASA mission operations. Our planning toolkit SPIFe (Scheduling and Planning Interface for Exploration) has supported a variety of missions and field tests, scheduling activities for Mars rovers as well as crew on-board International Space Station and NASA earth analogs. The scheduled plan is the integration of all the activities for the day/s. In turn, the agents (rovers, landers, spaceships, crew) execute from this schedule while the mission support team members (e.g., flight controllers) follow the schedule during execution. Over the last couple of years, our team has begun to research and validate methods that will better support users during realtime operations and execution of scheduled activities. Our team utilizes human-computer interaction principles to research user needs, identify workflow processes, prototype software aids, and user test these. This paper discusses three specific prototypes developed and user tested to support real-time operations: Score Mobile, Playbook, and Mobile Assistant for Task Execution (MATE).

  4. Aspects of job scheduling

    NASA Technical Reports Server (NTRS)

    Phillips, K.

    1976-01-01

    A mathematical model for job scheduling in a specified context is presented. The model uses both linear programming and combinatorial methods. While designed with a view toward optimization of scheduling of facility and plant operations at the Deep Space Communications Complex, the context is sufficiently general to be widely applicable. The general scheduling problem including options for scheduling objectives is discussed and fundamental parameters identified. Mathematical algorithms for partitioning problems germane to scheduling are presented.

  5. Optimizing Operating Room Scheduling.

    PubMed

    Levine, Wilton C; Dunn, Peter F

    2015-12-01

    This article reviews the management of an operating room (OR) schedule and use of the schedule to add value to an organization. We review the methodology of an OR block schedule, daily OR schedule management, and post anesthesia care unit patient flow. We discuss the importance of a well-managed OR schedule to ensure smooth patient care, not only in the OR, but throughout the entire hospital. PMID:26610624

  6. Staying in or moving away from structured activities: Explanations involving parents and peers.

    PubMed

    Persson, Andreas; Kerr, Margaret; Stattin, Håkan

    2007-01-01

    Adolescent participation in structured activities, meaning those with adult leaders, regular meetings, and skill-building activities, is related to good adjustment. Participation in unstructured, unsupervised, peer-oriented activities is related to poor adjustment. Structured activity participation is high in early adolescence and then declines, raising the question of why youths leave structured activities. The authors examined explanations involving parents and peers. They used longitudinal data from 861 youths (ages 13-17 years). Results showed that, compared with youths who stayed in structured activities, those who switched to hanging out on the streets were less likely to have peers in structured activities and had less positive feelings about the home context and more negative interactions with parents. In addition, delinquency predicted switching to hanging out in the streets and never joining structured activities in the first place. The results concerning parents support a theoretical explanation of how parents might unintentionally affect youths' leisure choices. Furthermore, the authors found some indications that positive feelings at home might protect youths who switch from structured activities to hanging out on the streets from increases in delinquency. PMID:17201519

  7. EOS distributed planning and scheduling prototype

    NASA Astrophysics Data System (ADS)

    Hull, Larry G.; Peters, Stephen F.; Davis, Randy

    Some of the more significant lessons learned during the development of the Earth Observing System (EOS) Distributed Planning and Scheduling Prototype are presented. The need for a central scheduler is not demonstrated. A mapping of scheduling and conflict-resolution responsibility across the nodes of the EOS distributed scheduling system is developed and shown to be both feasible and appropriate. Complex instrument scheduling is mostly accomplished at the ICC/IST (instrument control center/instrumental support terminal) with 'slidable' flexibility for slews and some kinds of calibrations resolved at the EOS Operations Center (EOC). All nodes have full visibility interinstrument contention for resource and environmental rights, e.g., vibration, thermal, and electromagnetic. The EOC assigns, by activity, initial action responsibility for conflict resolution to a node which is party to the conflict. Most interinstrument conflicts are resolved by the ICCs and ISTs during an intermediate scheduling phase while the EOC is negotiating a TDRS schedule with the NCC.

  8. EOS distributed planning and scheduling prototype

    NASA Technical Reports Server (NTRS)

    Hull, Larry G.; Peters, Stephen F.; Davis, Randy

    1993-01-01

    Some of the more significant lessons learned during the development of the Earth Observing System (EOS) Distributed Planning and Scheduling Prototype are presented. The need for a central scheduler is not demonstrated. A mapping of scheduling and conflict-resolution responsibility across the nodes of the EOS distributed scheduling system is developed and shown to be both feasible and appropriate. Complex instrument scheduling is mostly accomplished at the ICC/IST (instrument control center/instrumental support terminal) with 'slidable' flexibility for slews and some kinds of calibrations resolved at the EOS Operations Center (EOC). All nodes have full visibility interinstrument contention for resource and environmental rights, e.g., vibration, thermal, and electromagnetic. The EOC assigns, by activity, initial action responsibility for conflict resolution to a node which is party to the conflict. Most interinstrument conflicts are resolved by the ICCs and ISTs during an intermediate scheduling phase while the EOC is negotiating a TDRS schedule with the NCC.

  9. Involving postgraduate's students in undergraduate small group teaching promotes active learning in both

    PubMed Central

    Kalra, Ruchi; Modi, Jyoti Nath; Vyas, Rashmi

    2015-01-01

    Background: Lecture is a common traditional method for teaching, but it may not stimulate higher order thinking and students may also be hesitant to express and interact. The postgraduate (PG) students are less involved with undergraduate (UG) teaching. Team based small group active learning method can contribute to better learning experience. Aim: To-promote active learning skills among the UG students using small group teaching methods involving PG students as facilitators to impart hands-on supervised training in teaching and managerial skills. Methodology: After Institutional approval under faculty supervision 92 UGs and 8 PGs participated in 6 small group sessions utilizing the jigsaw technique. Feedback was collected from both. Observations: Undergraduate Feedback (Percentage of Students Agreed): Learning in small groups was a good experience as it helped in better understanding of the subject (72%), students explored multiple reading resources (79%), they were actively involved in self-learning (88%), students reported initial apprehension of performance (71%), identified their learning gaps (86%), team enhanced their learning process (71%), informal learning in place of lecture was a welcome change (86%), it improved their communication skills (82%), small group learning can be useful for future self-learning (75%). Postgraduate Feedback: Majority performed facilitation for first time, perceived their performance as good (75%), it was helpful in self-learning (100%), felt confident of managing students in small groups (100%), as facilitator they improved their teaching skills, found it more useful and better identified own learning gaps (87.5%). Conclusions: Learning in small groups adopting team based approach involving both UGs and PGs promoted active learning in both and enhanced the teaching skills of the PGs. PMID:26380201

  10. Physical, Cognitive, Social, and Emotional Mediators of Activity Involvement and Health in Later Life.

    PubMed

    Matz-Costa, Christina; Carr, Dawn C; McNamara, Tay K; James, Jacquelyn Boone

    2016-10-01

    The current study tests the indirect effect of activity-related physical activity, cognitive activity, social interaction, and emotional exchange on the relationship between activity involvement and health (physical and emotional) in later life. Longitudinal data from the Health and Retirement Study (N = 5,442) were used to estimate a series of linear regression models. We found significant indirect effects for social interaction and benefit to others (emotional exchange) on emotional health (depressive symptoms) and indirect effects for use of body and benefit to others (physical) on physical health (frailty). The most potent indirect effect associated with emotional and physical health was experienced by those engaged in all four domains (use of body, use of mind, social interaction, and benefit to others). While effect sizes are small and results should be interpreted with caution, findings shed light on ways in which public health interventions aimed toward increasing role engagement in later life could be improved. PMID:26429863

  11. Involvement of NADPH oxidases in suppression of cyclooxygenase-2 promoter-dependent transcriptional activities by sesamol

    PubMed Central

    Shimizu, Satomi; Ishigamori, Rikako; Fujii, Gen; Takahashi, Mami; Onuma, Wakana; Terasaki, Masaru; Yano, Tomohiro; Mutoh, Michihiro

    2015-01-01

    Cyclooxygenase-2 (COX-2) has been shown to play an important role in colon carcinogenesis. Moreover, one of the components of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, NADPH oxidase 1 (NOX1), dominantly expressed in the colon, is implicated in the pathogenesis of colon cancer. We have reported that sesamol, one of the lignans in sesame seeds, suppressed COX-2 gene transcriptional activity in human colon cancer cells, and also suppressed intestinal polyp formation in Apc-mutant mice. In the present study, we investigated the involvement of NADPH oxidase in the inhibition of COX-2 transcriptional activity by sesamol. We found that several NADPH oxidase inhibitors, such as apocynin, showed suppressive effects on COX-2 transcriptional activity. Moreover, sesamol significantly suppressed NOX1 mRNA levels in a dose-dependent manner. In addition, we demonstrated that knockdown of NOX1 successfully suppressed COX-2 transcriptional activity. These results suggest that inhibition of NADPH oxidase, especially NOX1, may be involved in the mechanism of the suppression of COX-2 transcriptional activity by sesamol. PMID:25759517

  12. Effect of an Activated Platelet Concentrate on Differentiated Cells Involved in Tissue Healing.

    PubMed

    Brini, Anna T; Ceci, Caterina; Taschieri, Silvio; Niada, Stefania; Lolato, Alessandra; Giannasi, Chiara; Mortellaro, Carmen; Del Fabbro, Massimo

    2016-05-01

    Tissue healing is a complex process involving several players such as cells and growth factors released from platelets upon activation. Today, platelet concentrates (PCs) are used in many different medical fields including oral, orthopaedic, and reconstructive surgery since they allow growth factors delivery to the injured site, aiming at enhancing tissue regeneration. The purpose of this in vitro study was to evaluate the effect of the acellular plasma of an activated platelet concentrate obtained using a manual protocol, on the proliferation, and biological activity of differentiated cells involved in tissue healing. Human osteoblasts and dermal fibroblasts were grown in serum-free medium supplemented with PC derived from several donors. Human osteoblast and human dermal fibroblast proliferation was assessed by MTT test after 7 days and cells were count up to 12-day incubation. Human osteoblast osteo-differentiation was tested after 7 and 14-day incubation by alkaline phosphatase assay. The addition of PC to the culture medium caused an increased proliferation with respect to cells grown in standard condition. The results of the present study suggest that PC supports the proliferation of terminally differentiated cells involved in wound healing and tissue regeneration, confirming its beneficial clinical application in regenerative therapies. PMID:27054419

  13. Satellite mission scheduling algorithm based on GA

    NASA Astrophysics Data System (ADS)

    Sun, Baolin; Mao, Lifei; Wang, Wenxiang; Xie, Xing; Qin, Qianqing

    2007-11-01

    The Satellite Mission Scheduling problem (SMS) involves scheduling tasks to be performed by a satellite, where new task requests can arrive at any time, non-deterministically, and must be scheduled in real-time. This paper describes a new Satellite Mission Scheduling problem based on Genetic Algorithm (SMSGA). In this paper, it investigates algorithmic approaches for determining an optimal or near-optimal sequence of tasks, allocated to a satellite payload over time, with dynamic tasking considerations. The simulation results show that the proposed approach is effective and efficient in applications to the real problems.

  14. Forest soil metagenome gene cluster involved in antifungal activity expression in Escherichia coli.

    PubMed

    Chung, Eu Jin; Lim, He Kyoung; Kim, Jin-Cheol; Choi, Gyung Ja; Park, Eun Jin; Lee, Myung Hwan; Chung, Young Ryun; Lee, Seon-Woo

    2008-02-01

    Using two forest soils, we previously constructed two fosmid libraries containing 113,700 members in total. The libraries were screened to select active antifungal clones using Saccharomyces cerevisiae as a target fungus. One clone from the Yuseong pine tree rhizosphere soil library, pEAF66, showed S. cerevisiae growth inhibition. Despite an intensive effort, active chemicals were not isolated. DNA sequence analysis and transposon mutagenesis of pEAF66 revealed 39 open reading frames (ORFs) and indicated that eight ORFs, probably in one transcriptional unit, might be directly involved in the expression of antifungal activity in Escherichia coli. The deduced amino acid sequences of eight ORFs were similar to those of the core genes encoding type II family polyketide synthases, such as the acyl carrier protein (ACP), ACP synthases, aminotransferase, and ACP reductase. The gene cluster involved in antifungal activity was similar in organization to the putative antibiotic production locus of Pseudomonas putida KT2440, although we could not select a similar active clone from the KT2440 genomic DNA library in E. coli. ORFs encoding ATP binding cassette transporters and membrane proteins were located at both ends of the antifungal gene cluster. Upstream ORFs encoding an IclR family response regulator and a LysR family response regulator were involved in the positive regulation of antifungal gene expression. Our results suggested the metagenomic approach as an alternative to search for novel antifungal antibiotics from unculturable soil bacteria. This is the first report of an antifungal gene cluster obtained from a soil metagenome using S. cerevisiae as a target fungus. PMID:18065615

  15. Beyond participation: the association between school extracurricular activities and involvement in violence across generations of immigration.

    PubMed

    Jiang, Xin; Peterson, Ruth D

    2012-03-01

    Participation in extracurricular activities is purported to protect the broad spectrum of youth from a host of behavioral risks. Yet, empirical research on the extent to which this assumption holds for involvement in violence by immigrant youth is limited. Thus, using data for 13,236 (51.8% female) adolescents from the National Longitudinal Study of Adolescent Health, this study explores how the relationship between extracurricular activities and youth violence varies by type of extracurricular activity profile (sports alone, non-sports alone, and a combination of sports and non-sports) and by generations of immigration (first, second, and third-plus). The sample is composed of 9.3% (n = 1,233) first-generation youth, 15.7% (n = 2,080) second generation, and 74.9% (n = 9,923) third-plus generation. The results reveal that adolescents from the third-plus generation (i.e., non-immigrant youth) who participate in non-sports alone or sports plus non-sports have lower odds of involvement in violence than adolescents from the same generation who do not participate in extracurricular activities. However, for first- and second-generation adolescents, participation in extracurricular activities is associated with higher rather than lower odds of violence compared to their non-participating counterparts. These findings challenge the viewpoint that participation in mainstream extracurricular activities as afforded by US schools is equally beneficial for all youth. They also call for additional research that explores why immigrant youth are less likely than non-immigrant youth to gain violence-reducing benefits when they participate in extracurricular activities. PMID:22167574

  16. Involvement of Activated Oxygen in Nitrate-Induced Senescence of Pea Root Nodules.

    PubMed Central

    Escuredo, P. R.; Minchin, F. R.; Gogorcena, Y.; Iturbe-Ormaetxe, I.; Klucas, R. V.; Becana, M.

    1996-01-01

    The effect of short-term nitrate application (10 mM, 0-4 d) on nitrogenase (N2ase) activity, antioxidant defenses, and related parameters was investigated in pea (Pisum sativum L. cv Frilene) nodules. The response of nodules to nitrate comprised two stages. In the first stage (0-2 d), there were major decreases in N2ase activity and N2ase-linked respiration and concomitant increases in carbon cost of N2ase and oxygen diffusion resistance of nodules. There was no apparent oxidative damage, and the decline in N2ase activity was, to a certain extent, reversible. The second stage (>2 d) was typical of a senescent, essentially irreversible process. It was characterized by moderate increases in oxidized proteins and catalytic Fe and by major decreases in antioxidant enzymes and metabolites. The restriction in oxygen supply to bacteroids may explain the initial decline in N2ase activity. The decrease in antioxidant protection is not involved in this process and is not specifically caused by nitrate, since it also occurs with drought stress. However, comparison of nitrate- and drought-induced senescence shows an important difference: there is no lipid degradation or lipid peroxide accumulation with nitrate, indicating that lipid peroxidation is not necessarily involved in nodule senescence. PMID:12226252

  17. The spectrum of nasal involvement in systemic lupus erythematosus and its association with the disease activity.

    PubMed

    Kusyairi, K A; Gendeh, B S; Sakthiswary, R; Shaharir, S S; Haizlene, A H; Yusof, K H

    2016-04-01

    The purpose of this study was to determine the spectrum of nasal involvement in systemic lupus erythematosus (SLE) and its association with the disease activity of SLE based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). This was a cross-sectional and observational study involving 73 stable SLE patients. All subjects were evaluated for the SLEDAI scores and had nasal endoscopic examination. The most commonly reported symptom was nasal congestion (31.5%) followed by nasal itchiness (26.0%), runny nose (20.5%) and nasal dryness (19.2%). Almost half (42.9%) of the subjects had nasal mucosal abnormalities, which included mucositis, crusting, ulceration, bifid middle turbinate, septal spur, Jacobson's organ, deviated nasal septum, bilateral inferior turbinate hypertrophy, everted uncinate process, nasopharynx cleft and torus palatinus. The median SLEDAI score for subjects with nasal symptoms was significantly higher than subjects without nasal symptoms (p < 0.05). Similarly, subjects with moderate to high activity (SLEDAI scores of 6-19) had a significantly higher frequency of both nasal symptoms and nasal mucosal abnormalities (p < 0.05) compared to subjects with no to mild activity (SLEDAI scores of 0-5). PMID:26657735

  18. An Initial Investigation of Sexual Minority Youth Involvement in School-Based Extracurricular Activities

    PubMed Central

    Russell, Stephen T.

    2012-01-01

    Sexual minority youth are at risk for negative school-based experiences and poor academic outcomes. Yet, little is known about their experiences in positive school-based contexts. Using the National Longitudinal Study of Adolescent Health (1,214 sexual minority and 11,427 heterosexual participants), this study compared participation rates in, predictors of, and outcomes associated with three types of school-based extracurricular activities - sports, arts, and school clubs - by sexual orientation and gender. Findings revealed several significant sexual orientation and gender differences in participation rates in school-based sports, clubs, and arts activities. Further, findings suggested that the outcomes associated with extracurricular activity involvement do not differ by sexual orientation and gender; however, predictors of participation in these domains varied across groups. PMID:24187476

  19. Psychosocial factors associated with youth involvement in community activities promoting heart health.

    PubMed

    Altman, D G; Feighery, E; Robinson, T N; Haydel, K F; Strausberg, L; Lorig, K; Killen, J D

    1998-08-01

    This study examined factors that influence youth participation in heart disease prevention activities among 2,609 ninth graders in six inner-city public high schools. Constructs derived from social cognitive, empowerment, and community development theories informed the conceptual framework employed. Study participants were diverse with respect to gender, ethnicity, parent education, acculturation, and academic achievement. Perceived incentive value, self-efficacy, outcome expectancies, sense of community, and perceived policy control were all significantly associated with participation in community activities promoting heart health. In multivariate analyses, perceived incentive value, defined as the extent to which participants valued a heart-healthy environment, was most strongly associated with community participation, accounting for 11.9% of the total variance. These findings have implications for designing school curricula and after-school and community programs targeting adolescents' involvement in health advocacy activities. PMID:9690106

  20. Oclacitinib (APOQUEL®) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy

    PubMed Central

    Gonzales, A J; Bowman, J W; Fici, G J; Zhang, M; Mann, D W; Mitton-Fry, M

    2014-01-01

    Janus kinase (JAK) enzymes are involved in cell signaling pathways activated by various cytokines dysregulated in allergy. The objective of this study was to determine whether the novel JAK inhibitor oclacitinib could reduce the activity of cytokines implicated in canine allergic skin disease. Using isolated enzyme systems and in vitro human or canine cell models, potency and selectivity of oclacitinib was determined against JAK family members and cytokines that trigger JAK activation in cells. Oclacitinib inhibited JAK family members by 50% at concentrations (IC50's) ranging from 10 to 99 nm and did not inhibit a panel of 38 non-JAK kinases (IC50's > 1000 nm). Oclacitinib was most potent at inhibiting JAK1 (IC50 = 10 nm). Oclacitinib also inhibited the function of JAK1-dependent cytokines involved in allergy and inflammation (IL-2, IL-4, IL-6, and IL-13) as well as pruritus (IL-31) at IC50's ranging from 36 to 249 nm. Oclacitinib had minimal effects on cytokines that did not activate the JAK1 enzyme in cells (erythropoietin, granulocyte/macrophage colony-stimulating factor, IL-12, IL-23; IC50's > 1000 nm). These results demonstrate that oclacitinib is a targeted therapy that selectively inhibits JAK1-dependent cytokines involved in allergy, inflammation, and pruritus and suggests these are the mechanisms by which oclacitinib effectively controls clinical signs associated with allergic skin disease in dogs. PMID:24495176

  1. Activated alveolar macrophage and lymphocyte alveolitis in extrathoracic sarcoidosis without radiological mediastinopulmonary involvement

    SciTech Connect

    Wallaert, B.; Ramon, P.; Fournier, E.C.; Prin, L.; Tonnel, A.B.; Voisin, C.

    1986-01-01

    Cellular characteristics of BAL were investigated in 18 patients with proved extrathoracic sarcoidosis (that is, sarcoidosis that affected the skin, eyes, parotid glands, stomach, nose, kidneys, or meninges) without clinical or radiological mediastinopulmonary involvement. Computed tomography of the thorax was performed on five patients: four patients were normal, and one had enlarged lymph nodes (these enlargements were not detectable on the patient's chest roentgenogram). The results of pulmonary function tests were normal in all patients. The total BAL cell count did not differ significantly between controls and patients. Abnormal percentages of alveolar lymphocytes (from 18 to 87%) were noted in 15 out of 18 patients. SACE levels were normal in 15 patients. No pulmonary gallium uptake was detected. The chemiluminescence of AM's, whether spontaneous or PMA induced, was increased in five out of seven patients. The percentages of T3+ lymphocytes in sarcoidosis patients did not significantly differ from those in controls. The T4+:T8+ ratio was normal in four patients and slightly increased in one. Follow-up of patients showed that alveolar lymphocytosis is as lasting as extrathoracic involvement. Our data demonstrate increased percentages of lymphocytes and activated AM's in the BAL of patients with extrathoracic sarcoidosis. This may be due to the initial involvement of the respiratory tract in extrathoracic sarcoidosis or to the diffusion of activated macrophages and lymphocytes from an extrathoracic site into the lung.

  2. Secretion of a lysophospholipase D activity by adipocytes: involvement in lysophosphatidic acid synthesis

    PubMed Central

    Gesta, Stéphane; Simon, Marie-Françoise; Rey, Astrid; Sibrac, David; Girard, Alexia; Lafontan, Max; Valet, Philippe; Saulnier-Blache, Jean Sébastien

    2002-01-01

    The aim of the present work was to depict the metabolic pathways involved in extra-cellular production of lysophosphatidic acid (LPA) by adipocytes. LPA was followed by quantifying the accumulation of LPA in the incubation medium (conditioned medium: CM) of 3T3F442A adipocytes, or human adipose tissue explants, using a radioenzymatic assay. Surprisingly, after separation from the cells, the amount of LPA present in CM could significantly be increased by further incubation at 37°C. This suggested the presence of a LPA-synthesizing activity (LPA-SA) in CM. LPA-SA appeared as a soluble activity which was inhibited by divalent ion chelators: EDTA and phenanthrolin. The effect of EDTA was preferentially reverted by CoCl2, as described for a lysophospholipase D- (lyso-PLD) activity previously identified in rat plasma. LPA concentration could also be increased by treatment with a bacterial PLD, demonstrating the presence of PLD-sensitive LPA-precursors (mainly lysophosphatidylcholine) in adipocyte CM. LPA-SA could be increased by addition of exogenous lysophosphatidylcholine, lysophosphatidylglycerol, or lyso-platelet activating factor, demonstrating that LPA-SA resulted from the action of a lyso-PLD. LPA-SA was not inhibited, but rather activated, by primary alcohol (ethanol and 1-butanol), suggesting that adipocyte lyso-PLD was not a classical PLD. Finally, LPA-SA was found to be weaker in CM of undifferentiated adipocyte (preadipocytes) as compared to CM of differentiated adipocytes. In conclusion, our results reveal the existence of a secreted lyso-PLD activity regulated during adipocyte-differentiation and involved in extra-cellular production of synthesis of LPA by adipocytes. PMID:12032165

  3. Anticancer Activities of Pterostilbene-Isothiocyanate Conjugate in Breast Cancer Cells: Involvement of PPARγ

    PubMed Central

    Nikhil, Kumar; Sharan, Shruti; Singh, Abhimanyu K.; Chakraborty, Ajanta; Roy, Partha

    2014-01-01

    Trans-3,5-dimethoxy-4′-hydroxystilbene (PTER), a natural dimethylated analog of resveratrol, preferentially induces certain cancer cells to undergo apoptosis and could thus have a role in cancer chemoprevention. Peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, is a ligand-dependent transcription factor whose activation results in growth arrest and/or apoptosis in a variety of cancer cells. Here we investigated the potential of PTER-isothiocyanate (ITC) conjugate, a novel class of hybrid compound (PTER-ITC) synthesized by appending an ITC moiety to the PTER backbone, to induce apoptotic cell death in hormone-dependent (MCF-7) and -independent (MDA-MB-231) breast cancer cell lines and to elucidate PPARγ involvement in PTER-ITC action. Our results showed that when pre-treated with PPARγ antagonists or PPARγ siRNA, both breast cancer cell lines suppressed PTER-ITC-induced apoptosis, as determined by annexin V/propidium iodide staining and cleaved caspase-9 expression. Furthermore, PTER-ITC significantly increased PPARγ mRNA and protein levels in a dose-dependent manner and modulated expression of PPARγ-related genes in both breast cancer cell lines. This increase in PPARγ activity was prevented by a PPARγ-specific inhibitor, in support of our hypothesis that PTER-ITC can act as a PPARγ activator. PTER-ITC-mediated upregulation of PPARγ was counteracted by co-incubation with p38 MAPK or JNK inhibitors, suggesting involvement of these pathways in PTER-ITC action. Molecular docking analysis further suggested that PTER-ITC interacted with 5 polar and 8 non-polar residues within the PPARγ ligand-binding pocket, which are reported to be critical for its activity. Collectively, our observations suggest potential applications for PTER-ITC in breast cancer prevention and treatment through modulation of the PPARγ activation pathway. PMID:25119466

  4. The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase.

    PubMed

    Zakikhani, Mahvash; Dowling, Ryan J O; Sonenberg, Nahum; Pollak, Michael N

    2008-10-01

    Population studies provide evidence that obesity and insulin resistance are associated not only with elevated serum insulin levels and reduced serum adiponectin levels but also with increased risk of aggressive prostate and colon cancer. We show here that adiponectin activates AMP-activated protein kinase (AMPK) in colon (HT-29) and prostate (PC-3) cancer cells. These results are consistent with prior observations in myocytes, but we show that in epithelial cancer cells AMPK activation is associated with reduction in mammalian target of rapamycin activation as estimated by Ser(2448) phosphorylation, with reduction in p70S6 kinase activation as estimated by Thr(389) phosphorylation, with ribosomal protein S6 activation as estimated by Ser(235/236) phosphorylation, with reduction in protein translation as estimated by [(35)S]methionine incorporation, and with growth inhibition. Adiponectin-induced growth inhibition is significantly attenuated when AMPK level is reduced using small interfering RNA, indicating that AMPK is involved in mediating the antiproliferative action of this adipokine. Thus, adiponectin has the characteristics of a AMPK-dependent growth inhibitor that is deficient in obesity, and this may contribute to the adverse effects of obesity on neoplastic disease. Furthermore, metformin was observed to activate AMPK and to have growth inhibitory actions on prostate and colon cancer cells, suggesting that this compound may be of particular value in attenuating the adverse effects of obesity on neoplasia. PMID:19138981

  5. Dedicated heterogeneous node scheduling including backfill scheduling

    DOEpatents

    Wood, Robert R.; Eckert, Philip D.; Hommes, Gregg

    2006-07-25

    A method and system for job backfill scheduling dedicated heterogeneous nodes in a multi-node computing environment. Heterogeneous nodes are grouped into homogeneous node sub-pools. For each sub-pool, a free node schedule (FNS) is created so that the number of to chart the free nodes over time. For each prioritized job, using the FNS of sub-pools having nodes useable by a particular job, to determine the earliest time range (ETR) capable of running the job. Once determined for a particular job, scheduling the job to run in that ETR. If the ETR determined for a lower priority job (LPJ) has a start time earlier than a higher priority job (HPJ), then the LPJ is scheduled in that ETR if it would not disturb the anticipated start times of any HPJ previously scheduled for a future time. Thus, efficient utilization and throughput of such computing environments may be increased by utilizing resources otherwise remaining idle.

  6. Maturation of suprathreshold auditory nerve activity involves cochlear CGRP-receptor complex formation.

    PubMed

    Dickerson, Ian M; Bussey-Gaborski, Rhiannon; Holt, Joseph C; Jordan, Paivi M; Luebke, Anne E

    2016-07-01

    In adult animals, the neuropeptide calcitonin gene-related peptide (CGRP) is contained in cochlear efferent fibers projecting out to the cochlea, and contributes to increased suprathreshold sound-evoked activity in the adult auditory nerve. Similarly, CGRP applied to the lateral-line organ (hair cell organ) increases afferent nerve activity in adult frogs (post-metamorphic day 30), yet this increase is developmentally delayed from post-metamorphic day 4-30. In this study, we discovered that there was also a developmental delay in increased suprathreshold sound-evoked activity auditory nerve between juvenile and adult mice similar to what had been observed previously in frog. Moreover, juvenile mice with a targeted deletion of the αCGRP gene [CGRP null (-/-)] did not show a similar developmental increase in nerve activity, suggesting CGRP signaling is involved. This developmental delay is not due to a delay in CGRP expression, but instead is due to a delay in receptor formation. We observed that the increase in sound-evoked nerve activity is correlated with increased formation of cochlear CGRP receptors, which require three complexed proteins (CLR, RAMP1, RCP) to be functional. CGRP receptor formation in the cochlea was incomplete at 1 month of age (juvenile), but complete by 3 months (adult), which corresponded to the onset of suprathreshold enhancement of sound-evoked activity in wild-type animals. Taken together, these data support a model for cochlear function that is enhanced by maturation of CGRP receptor complexes. PMID:27440744

  7. An investigation of the use of temporal decomposition in space mission scheduling

    NASA Technical Reports Server (NTRS)

    Bullington, Stanley E.; Narayanan, Venkat

    1994-01-01

    This research involves an examination of techniques for solving scheduling problems in long-duration space missions. The mission timeline is broken up into several time segments, which are then scheduled incrementally. Three methods are presented for identifying the activities that are to be attempted within these segments. The first method is a mathematical model, which is presented primarily to illustrate the structure of the temporal decomposition problem. Since the mathematical model is bound to be computationally prohibitive for realistic problems, two heuristic assignment procedures are also presented. The first heuristic method is based on dispatching rules for activity selection, and the second heuristic assigns performances of a model evenly over timeline segments. These heuristics are tested using a sample Space Station mission and a Spacelab mission. The results are compared with those obtained by scheduling the missions without any problem decomposition. The applicability of this approach to large-scale mission scheduling problems is also discussed.

  8. Involvement of nigral oxytocin in locomotor activity: A behavioral, immunohistochemical and lesion study in male rats.

    PubMed

    Angioni, Laura; Cocco, Cristina; Ferri, Gian-Luca; Argiolas, Antonio; Melis, Maria Rosaria; Sanna, Fabrizio

    2016-07-01

    Oxytocin is involved in the control of different behaviors, from sexual behavior and food consumption to empathy, social and affective behaviors. An imbalance of central oxytocinergic neurotransmission has been also associated with different mental pathologies, from depression, anxiety and anorexia/bulimia to schizophrenia, autism and drug dependence. This study shows that oxytocin may also play a role in the control of locomotor activity. Accordingly, intraperitoneal oxytocin (0.5-2000μg/kg) reduced locomotor activity of adult male rats. This effect was abolished by d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin, an oxytocin receptor antagonist, given into the lateral ventricles at the dose of 2μg/rat, which was ineffective on locomotor activity. Oxytocin (50-200ng/site) also reduced and d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (2μg/site) increased locomotor activity when injected bilaterally into the substantia nigra, a key area in the control of locomotor activity. Conversely, the destruction of nigral neurons bearing oxytocin receptors by the recently characterized neurotoxin oxytocin-saporin injected into the substantia nigra, increased basal locomotor activity. Since oxytocin-saporin injected into the substantia nigra caused a marked reduction of neurons immunoreactive for tyrosine hydroxylase (e.g., nigrostriatal dopaminergic neurons) and for vesicular glutamate transporters VGluT1, VGluT2 and VGluT3 (e.g., glutamatergic neurons), but not for glutamic acid decarboxylase (e.g., GABAergic neurons), together these findings suggest that oxytocin influences locomotor activity by acting on receptors localized presynaptically in nigral glutamatergic nerve terminals (which control the activity of nigral GABAergic efferent neurons projecting to brain stem nuclei controlling locomotor activity), rather than on receptors localized in the cell bodies/dendrites of nigrostriatal dopaminergic neurons. PMID:27189764

  9. Organized Activity Participation, Positive Youth Development, and the Over-Scheduling Hypothesis. Social Policy Report. Volume 20, Number 4

    ERIC Educational Resources Information Center

    Mahoney, Joseph L.; Harris, Angel L.; Eccles, Jacquelynne S.

    2006-01-01

    There is increasing awareness that how young people spend their time outside of school has consequences for their development. As part of this awareness, interest in organized activities--extracurricular activities, after-school programs, and youth organizations--has grown markedly. On balance, the bulk of research on organized activities has…

  10. The NALP3 inflammasome is involved in neurotoxic prion peptide-induced microglial activation

    PubMed Central

    2012-01-01

    Background Prion diseases are neurodegenerative disorders characterized by the accumulation of an abnormal disease-associated prion protein, PrPSc. In prion-infected brains, activated microglia are often present in the vicinity of PrPSc aggregates, and microglial activation is thought to play a key role in the pathogenesis of prion diseases. Although interleukin (IL)-1β release by prion-induced microglia has been widely reported, the mechanism by which primed microglia become activated and secrete IL-1β in prion diseases has not yet been elucidated. In this study, we investigated the role of the NACHT, LRR and PYD domains-containing protein (NALP)3 inflammasome in IL-1β release from lipopolysaccharide (LPS)-primed microglia after exposure to a synthetic neurotoxic prion fragment (PrP106-126). Methods The inflammasome components NALP3 and apoptosis-associated speck-like protein (ASC) were knocked down by gene silencing. IL-1β production was assessed using ELISA. The mRNA expression of NALP3, ASC, and pro-inflammatory factors was measured by quantitative PCR. Western blot analysis was used to detect the protein level of NALP3, ASC, caspase-1 and nuclear factor-κB. Results We found that that PrP106-126-induced IL-1β release depends on NALP3 inflammasome activation, that inflammasome activation is required for the synthesis of pro-inflammatory and chemotactic factors by PrP106-126-activated microglia, that inhibition of NF-κB activation abrogated PrP106-126-induced NALP3 upregulation, and that potassium efflux and production of reactive oxygen species were implicated in PrP106-126-induced NALP3 inflammasome activation in microglia. Conclusions We conclude that the NALP3 inflammasome is involved in neurotoxic prion peptide-induced microglial activation. To our knowledge, this is the first time that strong evidence for the involvement of NALP3 inflammasome in prion-associated inflammation has been found. PMID:22531291

  11. Lipopolysaccharide-induced Lung Injury Involves the Nitration-mediated Activation of RhoA*

    PubMed Central

    Rafikov, Ruslan; Dimitropoulou, Christiana; Aggarwal, Saurabh; Kangath, Archana; Gross, Christine; Pardo, Daniel; Sharma, Shruti; Jezierska-Drutel, Agnieszka; Patel, Vijay; Snead, Connie; Lucas, Rudolf; Verin, Alexander; Fulton, David; Catravas, John D.; Black, Stephen M.

    2014-01-01

    Acute lung injury (ALI) is characterized by increased endothelial hyperpermeability. Protein nitration is involved in the endothelial barrier dysfunction in LPS-exposed mice. However, the nitrated proteins involved in this process have not been identified. The activation of the small GTPase RhoA is a critical event in the barrier disruption associated with LPS. Thus, in this study we evaluated the possible role of RhoA nitration in this process. Mass spectroscopy identified a single nitration site, located at Tyr34 in RhoA. Tyr34 is located within the switch I region adjacent to the nucleotide-binding site. Utilizing this structure, we developed a peptide designated NipR1 (nitration inhibitory peptide for RhoA 1) to shield Tyr34 against nitration. TAT-fused NipR1 attenuated RhoA nitration and barrier disruption in LPS-challenged human lung microvascular endothelial cells. Further, treatment of mice with NipR1 attenuated vessel leakage and inflammatory cell infiltration and preserved lung function in a mouse model of ALI. Molecular dynamics simulations suggested that the mechanism by which Tyr34 nitration stimulates RhoA activity was through a decrease in GDP binding to the protein caused by a conformational change within a region of Switch I, mimicking the conformational shift observed when RhoA is bound to a guanine nucleotide exchange factor. Stopped flow kinetic analysis was used to confirm this prediction. Thus, we have identified a new mechanism of nitration-mediated RhoA activation involved in LPS-mediated endothelial barrier dysfunction and show the potential utility of “shielding” peptides to prevent RhoA nitration in the management of ALI. PMID:24398689

  12. Immunization Schedules for Adults

    MedlinePlus

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedules for Adults in Easy-to-read Formats ... previous immunizations. View or Print a Schedule Recommended Immunizations for Adults (19 Years and Older) by Age ...

  13. Childhood Immunization Schedule

    MedlinePlus

    ... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

  14. Lyn is involved in CD24-induced ERK1/2 activation in colorectal cancer

    PubMed Central

    2012-01-01

    Background and aim CD24 expression is associated with human colorectal cancer (CRC). Our previous data indicated that CD24 promoted the proliferation and invasion of colorectal cancer cells through the activation of ERK1/2. Since Src family kinases are frequently deregulated in CRC and closely related to the MAPK signaling pathway, we investigated the impact of Lyn, an important member of SFKs, on CD24-induced ERK1/2 activation in CRC. Methods and Results The interaction of CD24 and Lyn was identified by co-immunoprecipitation (Co-IP) and ectopic expression of CD24-induced Lyn activation. Inhibition of Lyn activation by phosphatase PP2 in SW480CD24cells abrogated CD24-induced invasion. The results of the Co-IP and immunofluorescence assay revealed that overexpression of CD24 enhanced the interaction of Lyn and ERK1/2 and induced the nuclear translocation of Lyn. However, inhibition of Lyn activity attenuated CD24-induced ERK1/2 activation, and depletion of CD24 disrupted Lyn-ERK1/2 interaction. Immunohistochemistry analysis for 202 cases of CRC showed that the expression of both CD24 and Lyn was positively correlated with tumor grade, stage, lymph node and distant metastasis. Patients with lower expression of CD24 or Lyn had a higher survival rate. The Cox multivariate analysis showed that CD24 expression, but not Lyn expression, was an independent prognostic factor of CRC. Conclusions Our results suggest that Lyn is involved in CD24-induced ERK1/2 activation in CRC. The expression of CD24 is associated with activation of Lyn and ERK1/2, which might be a novel mechanism related to CD24-mediated regulation of CRC development. PMID:22731636

  15. AMP-activated protein kinase is involved in perfluorohexanesulfonate -induced apoptosis of neuronal cells.

    PubMed

    Lee, Youn Ju; Choi, So-Young; Yang, Jae-Ho

    2016-04-01

    Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds (PFCs), has been used in a variety of industrial and consumer applications and detected in serum in the general population. This raised a concern over its possible detrimental health effects, including neurotoxic effects. We have previously shown that PFHxS induced neuronal apoptosis via the NMDA receptor-mediated extracellular signal-regulated kinase (ERK) pathway. Recently, it has been reported that AMP-activated protein kinase (AMPK) acts as a key signal molecule in neuronal excitotoxicity as well as providing a neuroprotective function. In the present study, we have examined the involvement of AMPK in PFHxS-induced neuronal apoptosis using neuronal differentiated PC12 cells. PFHxS induced significant increases in intracellular [Ca(2+)] via the NMDA receptor and the L-type voltage-gated calcium channel (L-VGCC). The inhibition of Ca(2+) loading by the NMDA receptor antagonist, MK801 and the L-VGCC blockers, nifedipine and diltiazem significantly reduced PFHxS-induced apoptosis. PFHxS induced sustained activation of AMPK and the inhibition of AMPK activation by compound C and AMPK siRNA significantly reduced PFHxS-induced caspase-3 activity. These results indicate the pro-apoptotic role of AMPK. The activation of AMPK was attenuated by MK801, nifedipine and diltiazem. However, the activation of AMPK was not affected by the ERK inhibitor, PD98059. Likewise, ERK activation was not affected by compound C but was substantially reduced by MK801, nifedipine or diltiazem. This suggests that the activation of AMPK and ERK is regulated by intracellular Ca(2+) loading in distinct pathways. Taken together, PFHxS-induced neuronal apoptosis is mediated by AMPK and ERK pathways, which are distinctly regulated by increased intracellular Ca(2+) via the NMDA receptor and L-VGCC. PMID:26826296

  16. Involvement of microglia activation in the lead induced long-term potentiation impairment.

    PubMed

    Liu, Ming-Chao; Liu, Xin-Qin; Wang, Wen; Shen, Xue-Feng; Che, Hong-Lei; Guo, Yan-Yan; Zhao, Ming-Gao; Chen, Jing-Yuan; Luo, Wen-Jing

    2012-01-01

    Exposure of Lead (Pb), a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP) as well as hippocampal neuronal injury. Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks) caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits. PMID:22952811

  17. The benefits of in-group contact through physical activity involvement for health and well-being among Korean immigrants

    PubMed Central

    Kim, Junhyoung; Heo, Jinmoo; Kim, Jun

    2014-01-01

    This qualitative study is designed to examine the benefits of physical activity involvement with members of the same ethnic group. For this study, Korean immigrants who were members of Korean physical activity clubs such as badminton and tennis were selected as participants. Using a constructive grounded theory methodology, three themes were identified as benefits of physical activity involvement: (1) the experience of psychological well-being, (2) the creation of a unique cultural world, and (3) the facilitation of physical activity involvement. The findings of this study suggest that Korean immigrant participants gained various social, cultural, and psychological benefits by engaging in activities with other Korean immigrants. PMID:24875239

  18. The benefits of in-group contact through physical activity involvement for health and well-being among Korean immigrants.

    PubMed

    Kim, Junhyoung; Heo, Jinmoo; Kim, Jun

    2014-01-01

    This qualitative study is designed to examine the benefits of physical activity involvement with members of the same ethnic group. For this study, Korean immigrants who were members of Korean physical activity clubs such as badminton and tennis were selected as participants. Using a constructive grounded theory methodology, three themes were identified as benefits of physical activity involvement: (1) the experience of psychological well-being, (2) the creation of a unique cultural world, and (3) the facilitation of physical activity involvement. The findings of this study suggest that Korean immigrant participants gained various social, cultural, and psychological benefits by engaging in activities with other Korean immigrants. PMID:24875239

  19. Tyrosine phosphorylation and protein degradation control the transcriptional activity of WRKY involved in benzylisoquinoline alkaloid biosynthesis.

    PubMed

    Yamada, Yasuyuki; Sato, Fumihiko

    2016-01-01

    Benzylisoquinoline alkaloids (BIQ) are among the most structurally diverse and pharmaceutically valuable secondary metabolites. A plant-specific WRKY-type transcription factor, CjWRKY1, was isolated from Coptis japonica and identified as a transcriptional activator of BIQ biosynthesis. However, the expression of CjWRKY1 gene alone was not sufficient for the activation of genes encoding biosynthetic enzymes. Here, we report the importance of post-translational regulation of CjWRKY1 in BIQ biosynthesis. First, we detected the differential accumulation of CjWRKY1 protein in two cell lines with similar CjWRKY1 gene expression but different levels of accumulated alkaloids. Further investigation of the WRKY protein identified the phosphorylation of the WRKYGQK core domain at Y115. The CjWRKY(Y115E) phosphorylation-mimic mutant showed loss of nuclear localization, DNA-binding activity, and transactivation activity compared to wild-type CjWRKY1. Rapid degradation of the CjWRKY1 protein was also confirmed following treatment with inhibitors of the 26S proteasome and protease inhibitors. The existence of two independent degradation pathways as well as protein phosphorylation suggests the fine-tuning of CjWRKY1 activities is involved in the regulation of biosynthesis of BIQs. PMID:27552928

  20. Ca2+-calcineurin signaling is involved in norepinephrine-induced cardiac fibroblasts activation

    PubMed Central

    Tian, Chun-Jing; Pang, Xiao

    2015-01-01

    Cardiac fibroblasts (CFs) activation plays a vital role in cardiac fibrosis. There are some studies demonstrate that norepinephrine (NE, an α1-adrenoceptor agonist) induced CFs proliferation. But whether Ca2+-calcineurin, a signaling concerned with growth and differentiation in various cell types, is participated in NE-induced CFs activation is unclear. In present study, we determined NE-induced CFs proliferation and differentiation, synthesis of collagen, and calcineurin (CaN) activity, and the effects of phentolamine (Phen, an α1-adrenoceptor antagonist), verapamil (Ver, a calcium channel blocker) and cyclosporine A (CsA, an inhibitor of CaN) on NE-induced CFs activation. The results showed that NE induced CFs proliferation and differentiation, increased α-SMA protein expression, increased collagen I, collagen III and fibronectin production, promoted ECM expression, activated CaN and increased CaN protein expression, which were inhibited by Phen, Ver and CsA. In vivo, more collagen deposition could be observed and total collagen volume fraction (CVF) was significantly increased in NE group. Phen, Ver and CsA decreased NE-induced collagen deposition, reduced cardiac fibrosis. Thus, our results demonstrate that Ca2+/CaN is involved in NE-induced CFs proliferation and collagen synthesis. PMID:26191219

  1. Tyrosine phosphorylation and protein degradation control the transcriptional activity of WRKY involved in benzylisoquinoline alkaloid biosynthesis

    PubMed Central

    Yamada, Yasuyuki; Sato, Fumihiko

    2016-01-01

    Benzylisoquinoline alkaloids (BIQ) are among the most structurally diverse and pharmaceutically valuable secondary metabolites. A plant-specific WRKY-type transcription factor, CjWRKY1, was isolated from Coptis japonica and identified as a transcriptional activator of BIQ biosynthesis. However, the expression of CjWRKY1 gene alone was not sufficient for the activation of genes encoding biosynthetic enzymes. Here, we report the importance of post-translational regulation of CjWRKY1 in BIQ biosynthesis. First, we detected the differential accumulation of CjWRKY1 protein in two cell lines with similar CjWRKY1 gene expression but different levels of accumulated alkaloids. Further investigation of the WRKY protein identified the phosphorylation of the WRKYGQK core domain at Y115. The CjWRKYY115E phosphorylation-mimic mutant showed loss of nuclear localization, DNA-binding activity, and transactivation activity compared to wild-type CjWRKY1. Rapid degradation of the CjWRKY1 protein was also confirmed following treatment with inhibitors of the 26S proteasome and protease inhibitors. The existence of two independent degradation pathways as well as protein phosphorylation suggests the fine-tuning of CjWRKY1 activities is involved in the regulation of biosynthesis of BIQs. PMID:27552928

  2. Inhibition of Fast Axonal Transport by Pathogenic SOD1 Involves Activation of p38 MAP Kinase

    PubMed Central

    Morfini, Gerardo A.; Bosco, Daryl A.; Brown, Hannah; Gatto, Rodolfo; Kaminska, Agnieszka; Song, Yuyu; Molla, Linda; Baker, Lisa; Marangoni, M. Natalia; Berth, Sarah; Tavassoli, Ehsan; Bagnato, Carolina; Tiwari, Ashutosh; Hayward, Lawrence J.; Pigino, Gustavo F.; Watterson, D. Martin; Huang, Chun-Fang; Banker, Gary; Brown, Robert H.; Brady, Scott T.

    2013-01-01

    Dying-back degeneration of motor neuron axons represents an established feature of familial amyotrophic lateral sclerosis (FALS) associated with superoxide dismutase 1 (SOD1) mutations, but axon-autonomous effects of pathogenic SOD1 remained undefined. Characteristics of motor neurons affected in FALS include abnormal kinase activation, aberrant neurofilament phosphorylation, and fast axonal transport (FAT) deficits, but functional relationships among these pathogenic events were unclear. Experiments in isolated squid axoplasm reveal that FALS-related SOD1 mutant polypeptides inhibit FAT through a mechanism involving a p38 mitogen activated protein kinase pathway. Mutant SOD1 activated neuronal p38 in mouse spinal cord, neuroblastoma cells and squid axoplasm. Active p38 MAP kinase phosphorylated kinesin-1, and this phosphorylation event inhibited kinesin-1. Finally, vesicle motility assays revealed previously unrecognized, isoform-specific effects of p38 on FAT. Axon-autonomous activation of the p38 pathway represents a novel gain of toxic function for FALS-linked SOD1 proteins consistent with the dying-back pattern of neurodegeneration characteristic of ALS. PMID:23776455

  3. Schedule Risk Assessment

    NASA Technical Reports Server (NTRS)

    Smith, Greg

    2003-01-01

    Schedule Risk Assessment needs to determine the probability of finishing on or before a given point in time. Task in a schedule should reflect the "most likely" duration for each task. IN reality, each task is different and has a varying degree of probability of finishing within or after the duration specified. Schedule risk assessment attempt to quantify these probabilities by assigning values to each task. Bridges the gap between CPM scheduling and the project's need to know the likelihood of "when".

  4. Reinforcement learning in scheduling

    NASA Technical Reports Server (NTRS)

    Dietterich, Tom G.; Ok, Dokyeong; Zhang, Wei; Tadepalli, Prasad

    1994-01-01

    The goal of this research is to apply reinforcement learning methods to real-world problems like scheduling. In this preliminary paper, we show that learning to solve scheduling problems such as the Space Shuttle Payload Processing and the Automatic Guided Vehicle (AGV) scheduling can be usefully studied in the reinforcement learning framework. We discuss some of the special challenges posed by the scheduling domain to these methods and propose some possible solutions we plan to implement.

  5. Schedules of controlled substances: rescheduling of hydrocodone combination products from schedule III to schedule II. Final rule.

    PubMed

    2014-08-22

    With the issuance of this final rule, the Administrator of the Drug Enforcement Administration reschedules hydrocodone combination products from schedule III to schedule II of the Controlled Substances Act. This scheduling action is pursuant to the Controlled Substances Act which requires that such actions be made on the record after opportunity for a hearing through formal rulemaking. This action imposes the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule II controlled substances on persons who handle (manufacture, distribute, dispense, import, export, engage in research, conduct instructional activities with, conduct chemical analysis with, or possess) or propose to handle hydrocodone combination products. PMID:25167591

  6. Parallel scheduling algorithms

    SciTech Connect

    Dekel, E.; Sahni, S.

    1983-01-01

    Parallel algorithms are given for scheduling problems such as scheduling to minimize the number of tardy jobs, job sequencing with deadlines, scheduling to minimize earliness and tardiness penalties, channel assignment, and minimizing the mean finish time. The shared memory model of parallel computers is used to obtain fast algorithms. 26 references.

  7. Block Scheduling. Research Brief

    ERIC Educational Resources Information Center

    Muir, Mike

    2003-01-01

    What are the effects of block scheduling? Results of transitioning from traditional to block scheduling are mixed. Some studies indicate no change in achievement results, nor change in teachers' opinions about instructional strategies. Other studies show that block scheduling doesn't work well for Advanced Placement or Music courses, that "hard to…

  8. NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells

    SciTech Connect

    Pecorelli, Alessandra; Bocci, Velio; Acquaviva, Alessandra; Belmonte, Giuseppe; Gardi, Concetta; Virgili, Fabio; Ciccoli, Lucia; Valacchi, Giuseppe

    2013-02-15

    During the last decade, it has been shown that the activation of NRF2 and the binding to electrophile-responsive element (EpREs), stimulates the expression of a great number of genes responsible for the synthesis of phase I and phase II proteins, including antioxidants enzymes and heme oxygenase-1 (HO-1). This critical cell response occurs in cardiovascular, degenerative and chronic infective diseases aggravated by a chronic oxidative stress. In our previous reports we have shown that ozonated plasma is able to up-regulate HO-1 expression in endothelial cells. In the present work we investigated a candidate mechanism involved in this process. After treatment with increasing doses of ozonated serum (20, 40 and 80 μg/mL O{sub 3} per mL of serum), a clear dose dependent activation of NRF2 and the subsequent induction of HO-1 and NAD(P)H quinone oxidoreductase 1(NQO1) was observed. This effect was also present when cells were treated with serum and hydrogen peroxide (H{sub 2}O{sub 2}) or serum and 4-hydroxynonenal (4HNE). Moreover, the treatment with ozonated serum was associated with a dose-dependent activation of extracellular-signal-regulated kinases (ERK1/2) and p38 MAP kinases (p38), not directly involved in NRF2 activation. These data, provide a new insight on the mechanism responsible for the induction of HO-1 expression by ozonated serum in the endothelium, and have a practical importance as an expedient approach to the treatment of patients with both effective orthodox drugs and ozonated autohemotherapy, targeted to the restoration of redox homeostasis. - Highlights: ► Endothelial HO1 is upregulated by ozonated plasma ► This activation is induced by NRF2 and it is ERK independent. ► 4HNE and H{sub 2}O{sub 2} are the main molecules involved in this process. ► Ozonated plasma induced a hormetic effect ► Combination of orthodox medicine and ozonated plasma can be a useful treatment.

  9. Cissus sicyoides: Pharmacological Mechanisms Involved in the Anti-Inflammatory and Antidiarrheal Activities

    PubMed Central

    Beserra, Fernando Pereira; de Cássia Santos, Raquel; Périco, Larissa Lucena; Rodrigues, Vinicius Peixoto; de Almeida Kiguti, Luiz Ricardo; Saldanha, Luiz Leonardo; Pupo, André Sampaio; da Rocha, Lúcia Regina Machado; Dokkedal, Anne Lígia; Vilegas, Wagner; Hiruma-Lima, Clélia Akiko

    2016-01-01

    The objective of this study was to evaluate the pharmacological mechanisms involved in anti-inflammatory and antidiarrheal actions of hydroalcoholic extract obtained from the leaves of Cissus sicyoides (HECS). The anti-inflammatory effect was evaluated by oral administration of HECS against acute model of edema induced by xylene, and the mechanisms of action were analysed by involvement of arachidonic acid (AA) and prostaglandin E2 (PGE2). The antidiarrheal effect of HECS was observed and we analyzed the motility and accumulation of intestinal fluid. We also analyzed the antidiarrheal mechanisms of action of HECS by evaluating the role of the opioid receptor, α2 adrenergic receptor, muscarinic receptor, nitric oxide (NO) and PGE2. The oral administration of HECS inhibited the edema induced by xylene and AA and was also able to significantly decrease the levels of PGE2. The extract also exhibited significant anti-diarrheal activity by reducing motility and intestinal fluid accumulation. This extract significantly reduced intestinal transit stimulated by muscarinic agonist and intestinal secretion induced by PGE2. Our data demonstrate that the mechanism of action involved in the anti-inflammatory effect of HECS is related to PGE2. The antidiarrheal effect of this extract may be mediated by inhibition of contraction by acting on the intestinal smooth muscle and/or intestinal transit. PMID:26805827

  10. A review of two recent occurrences at the Advanced Test Reactor involving subcontractor activities

    SciTech Connect

    Dahlke, H.J.; Jensen, N.C.; Vail, J.A.

    1997-11-01

    This report documents the results of a brief, unofficial investigation into two incidents at the Idaho National Engineering and Environmental Laboratory (INEEL) Advanced Test Reactor (ATR) facility, reported on October 25 and 31, 1997. The first event was an unanticipated breach of confinement. The second involved reactor operation with an inoperable seismic scram subsystem, violating the reactor`s Technical Specifications. These two incidents have been found to be unrelated. A third event that occurred on December 16, 1996, is also discussed because of its similarities to the first event listed above. Both of these incidents were unanticipated breaches of confinement, and both involved the work of construction subcontractor personnel. The cause for the subcontractor related occurrences is a work control process that fails to effectively interface with LMITCO management. ATR Construction Project managers work sufficient close with construction subcontractor personnel to understand planned day-to-day activities. They also have sufficient training and understanding of reactor operations to ensure adherence to applicable administrative requirements. However, they may not be sufficiently involved in the work authorization and control process to bridge an apparent communications gap between subcontractor employees and Facility Operations/functional support personnel for work inside the reactor facility. The cause for the inoperable seismic scram switch (resulting from a disconnected lead) is still under investigation. It does not appear to be subcontractor related.

  11. Pathways Involved in the Synergistic Activation of Macrophages by Lipoteichoic Acid and Hemoglobin

    PubMed Central

    Cox, Kathleen H.; Cox, Michelle E.; Woo-Rasberry, Virginia; Hasty, David L.

    2012-01-01

    Lipoteichoic acid (LTA) is a Gram-positive cell surface molecule that is found in both a cell-bound form and cell-free form in the host during an infection. Hemoglobin (Hb) can synergize with LTA, a TLR2 ligand, to potently activate macrophage innate immune responses in a TLR2- and TLR4-dependent way. At low levels of LTA, the presence of Hb can result in a 200-fold increase in the secretion of IL-6 following macrophage activation. Six hours after activation, the macrophage genes that are most highly up-regulated by LTA plus Hb activation compared to LTA alone are cytokines, chemokines, receptors and interferon-regulated genes. Several of these genes exhibit a unique TLR4-dependent increase in mRNA levels that continued to rise more than eight hours after stimulation. This prolonged increase in mRNA levels could be the result of an extended period of NF-κB nuclear localization and the concurrent absence of the NF-κB inhibitor, IκBα, after stimulation with LTA plus Hb. Dynasore inhibition experiments indicate that an endocytosis-dependent pathway is required for the TLR4-dependent up-regulation of IL-6 secretion following activation with LTA plus Hb. In addition, interferon-β mRNA is present after activation with LTA plus Hb, suggesting that the TRIF/TRAM-dependent pathway may be involved. Hb alone can elicit the TLR4-dependent secretion of TNF-α from macrophages, so it may be the TLR4 ligand. Hb also led to secretion of high mobility group box 1 protein (HMGB1), which synergized with LTA to increase secretion of IL-6. The activation of both the TLR2 and TLR4 pathways by LTA plus Hb leads to an enhanced innate immune response. PMID:23071790

  12. The insulin receptor C-terminus is involved in regulation of the receptor kinase activity.

    PubMed

    Kaliman, P; Baron, V; Alengrin, F; Takata, Y; Webster, N J; Olefsky, J M; Van Obberghen, E

    1993-09-21

    During the insulin receptor activation process, ligand binding and autophosphorylation induce two distinct conformational changes in the C-terminal domain of the receptor beta-subunit. To analyze the role of this domain and the involvement of the C-terminal autophosphorylation sites (Tyr1316 and Tyr1322) in receptor activation, we used (i) antipeptide antibodies against three different C-terminal sequences (1270-1281, 1294-1317, and 1309-1326) and (ii) an insulin receptor mutant (Y/F2) where Tyr1316 and Tyr1322 have been replaced by Phe. We show that the autophosphorylation-induced C-terminal conformational change is preserved in the Y/F2 receptor, indicating that this change is not induced by phosphorylation of the C-terminal sites but most likely by phosphorylation of the major sites in the kinase domain (Tyr1146, Tyr1150, and Tyr1151). Binding of antipeptide antibodies to the C-terminal domain modulated (activated or inhibited) both mutant and wild-type receptor-mediated phosphorylation of poly(Glu/Tyr). In contrast to the wild-type receptor, Y/F2 exhibited the same C-terminal configuration before and after insulin binding, evidencing that mutation of Tyr1316 and Tyr1322 introduced conformational changes in the C-terminus. Finally, the mutant receptor was 2-fold more active than the wild-type receptor for poly(Glu/Tyr) phosphorylation. In conclusion, the whole C-terminal region of the insulin receptor beta-subunit is likely to exert a regulatory influence on the receptor kinase activity. Perturbations of the C-terminal region, such as binding of antipeptides or mutation of Tyr1316 and Tyr1322, provoke alterations at the receptor kinase level, leading to activation or inhibition of the enzymic activity. PMID:7690586

  13. Identification of key residues involved in the activation and signaling properties of dopamine D3 receptor.

    PubMed

    Kota, Kokila; Kuzhikandathil, Eldo V; Afrasiabi, Milad; Lacy, Brett; Kontoyianni, Maria; Crider, A Michael; Song, Daniel

    2015-09-01

    The dopamine D3 receptor exhibits agonist-dependent tolerance and slow response termination (SRT) signaling properties that distinguish it from the closely-related D2 receptors. While amino acid residues important for D3 receptor ligand binding have been identified, the residues involved in activation of D3 receptor signaling and induction of signaling properties have not been determined. In this paper, we used cis and trans isomers of a novel D3 receptor agonist, 8-OH-PBZI, and site-directed mutagenesis to identify key residues involved in D3 receptor signaling function. Our results show that trans-8-OH-PBZI, but not cis-8-OH-PBZI, elicit the D3 receptor tolerance and SRT properties. We show that while both agonists require a subset of residues in the orthosteric binding site of D3 receptors for activation of the receptor, the ability of the two isomers to differentially induce tolerance and SRT is mediated by interactions with specific residues in the sixth transmembrane helix and third extracellular loop of the D3 receptor. We also show that unlike cis-8-OH-PBZI, which is a partial agonist at the dopamine D2S receptor and full agonist at dopamine D2L receptor, trans-8-OH-PBZI is a full agonist at both D2S and D2L receptors. The different effect of the two isomers on D3 receptor signaling properties and D2S receptor activation correlated with differential effects of the isomers on agonist-induced mouse locomotor activity. The two isomers of 8-OH-PBZI represent novel pharmacological tools for in silico D3 and D2 receptor homology modeling and for determining the role of D3 receptor tolerance and SRT properties in signaling and behavior. PMID:26116441

  14. Antidepressant-like activity of dehydrozingerone: involvement of the serotonergic and noradrenergic systems.

    PubMed

    Martinez, Débora M; Barcellos, Angelita; Casaril, Angela M; Savegnago, Lucielli; Lernardão, Eder J

    2014-12-01

    Dehydrozingerone (DHZ) is a phenolic compound isolated from ginger rhizomes (Zingiber officinale). It is known for its diverse spectrum of biological activities as an antioxidant, anti-inflammatory and antitumor compound. The present study was designed to assess the antidepressant effect of DHZ and the involvement of the monoaminergic system and to evaluate its in vitro antioxidant activity in the hippocampus, cortex and cerebellum of mice. For this study, the tail suspension test (TST), forced swim test (FST) and yohimbine lethality test were performed. DHZ administered orally 30min prior to testing reduced the immobility time in the TST (1-40mg/kg) and the FST (10-40mg/kg), with no change in locomotor activity in the open field test. The antidepressant-like effect of DHZ (1mg/kg) was prevented by ketanserin (1mg/kg, i.p.; a 5-HT2A/2C receptor antagonist), ondansetron (1mg/kg, i.p.; a 5-HT3 receptor antagonist), prazosin (1mg/kg, i.p., an α1-adrenoceptor antagonist) and yohimbine (1mg/kg, i.p., an α2-adrenoceptor antagonist) pretreatments. Furthermore, DHZ administered at doses of 10 and 20mg/kg increased the lethality of yohimbine (35mg/kg, i.p.). DHZ had antioxidant activity on in vitro lipid peroxidation induced by sodium nitroprusside in all brain regions tested. The results revealed that DHZ has a potent antidepressant effect, which seems to involve the serotonergic and noradrenergic systems. PMID:25449795

  15. Involvement of trigeminal subnucleus caudalis (medullary dorsal horn) in craniofacial nociceptive reflex activity.

    PubMed

    Tsai, C M; Chiang, C Y; Yu, X M; Sessle, B J

    1999-05-01

    We have previously shown that an increase in electromyographic (EMG) activity of digastric (DIG) and masseter (MASS) muscles can be reflexly evoked by injection into the rat's temporomandibular joint (TMJ) region of the small-fibre excitant and inflammatory irritant mustard oil (MO). Since the trigeminal (V) subnucleus caudalis (Vc, i.e. medullary dorsal horn) has traditionally been viewed as an essential brainstem relay site of nociceptive information from craniofacial tissues, an EMG study was carried out in 45 anaesthetized rats to determine if Vc is involved in the MO-evoked increases in jaw muscle EMG activity. The effects of histologically confirmed surgical or chemical lesions of Vc on this evoked EMG activity were tested in different groups of rats. MO injection into the left TMJ region of intact rats evoked bilateral increases in EMG activity of DIG and MASS which could be significantly reduced by surgical transection of the left caudal brainstem at the obex level; MO injection into the right TMJ region in these same rats still readily evoked increases in EMG activity. A sagittal section medial to Vc or transection at the level of the second cervical spinal segment did not produce any significant reduction in the reflexly evoked EMG activity. Neurones in Vc, as opposed to fibres of passage, appear to be important for the MO-evoked EMG activity, since injection into Vc of the neurotoxic chemical ibotenic acid significantly reduced the mustard oil-evoked EMG activity. The Vc also appears to play a role in the activation of contralateral V motoneurons, as evidenced by the activation of the contralateral DIG and MASS muscles by the injection of MO into the left TMJ region of intact rats and by the reduction of this evoked EMG activity in the contralateral DIG and MASS of rats with a surgical transection or ibotenic acid lesion of the left Vc. These findings suggest that Vc may be a critical element in the neural pathways underlying the reflex responses evoked

  16. The Role of Physical Activity and Feeding Schedule on the Kinetics of Inhaled and Oral Toluene in Rats

    EPA Science Inventory

    This manuscript provides new information regarding factors that affect the toxicokinetics of toluene, a hazardous air pollutant with acute neurotoxic activity. Toluene is a prototype compound of the class of volatile organic compounds (VOCs), which have similar CNS activity and k...

  17. Detecting cardiac involvement with magnetic resonance in patients with active eosinophilic granulomatosis with polyangiitis.

    PubMed

    Yune, Sehyo; Choi, Dong-Chull; Lee, Byung-Jae; Lee, Jin-Young; Jeon, Eun-Seok; Kim, Sung Mok; Choe, Yeon Hyeon

    2016-06-01

    Cardiac involvement is the most important prognostic factor in eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). The aims of this study were to describe findings of cardiac magnetic resonance (CMR) in patients with active EGPA and to find factors associated with cardiac involvement detected by CMR that could help identify patients who would benefit from the examination. Medical records and CMR images in 16 consecutive EGPA patients (8 women and 8 men, median age of 47 years ranging from 34 to 68 years) were reviewed. Clinical features and results of laboratory tests were compared according to the presence of myocardial late gadolinium enhancement (LGE) on CMR images. The patients were followed for the development of cardiac symptoms and signs (mean follow up duration, 40.5 ± 12.8 months). Among the total of 16 patients, 8 (50 %) had myocardial LGE according to CMR, located in the subendocardial layer in 7 of them (87.5 %). The extent of LGE had a significant negative correlation with left ventricular ejection fraction (LVEF, ρ = -0.723, p = 0.043). The presence of LGE was associated with larger end-systolic left ventricle internal dimension (34 vs. 28 mm, p = 0.027) and presence of diastolic dysfunction (75 vs. 0 %, p = 0.008) on echocardiography, elevated NT-proBNP (75 vs. 12.5 %, p = 0.012), and elevated CK-MB (62.5 vs. 0 %, p = 0.010) compared to the group without LGE. Only one patient (6.3 %) had cardiac symptoms before CMR and another patient (6.3 %) developed heart failure 4 years later during remission. The other 14 patients remained free from cardiac signs and symptoms during the follow-up period. In patients with active EGPA, CMR enables detection of cardiac involvement when cardiac symptoms are not present. Echocardiographic diastolic dysfunction and elevated NT-proBNP or CK-MB may help identify active EGPA patients who can benefit from CMR to detect cardiac involvement without cardiac symptoms. PMID

  18. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  19. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  20. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  1. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  2. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  3. 30 CFR 57.4660 - Work in shafts, raises, or winzes and other activities involving hazard areas.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... activities involving hazard areas. 57.4660 Section 57.4660 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS... Work in shafts, raises, or winzes and other activities involving hazard areas. During performance of...

  4. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  5. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  6. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  7. Multidimensional Self-Concept: Age and Gender Differences in Australian High School Students Involved in Delinquent Activities

    ERIC Educational Resources Information Center

    Carroll, Annemaree; Houghton, Stephen; Wood, Robert; Perkins, Catherine; Bower, Julie

    2007-01-01

    The present research examined the relationship between self-concept and level of involvement in delinquent activities of 1327 (612 males, 715 females) years 8-12 high school students. Through cluster analysis, participants were identified as having either high or low involvement in delinquent activities from scores on a self-report measure of…

  8. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  9. 12 CFR 408.4 - Early involvement in foreign activities for which Eximbank financing may be requested.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Early involvement in foreign activities for... Implementing Procedures § 408.4 Early involvement in foreign activities for which Eximbank financing may be requested. (a) Section 1501.2(d) of the NEPA Regulations requires agencies to provide for early...

  10. Who's who in the crew? Exploring participant involvement in the Active Living Coalition.

    PubMed

    Barnes, Priscilla A; Schaefer, Samantha; Middlestadt, Susan; Knoblock, Heidi

    2015-06-01

    Health coalitions serve as an important "vehicle" to strengthen horizontal and vertical ties between organizations, community groups, and individuals whose intent and purpose is to improve wellness. Having a strong and diverse group of participants is essential for highly effective coalitions to carry out their mission in an organized and participatory manner. However, the extent that individuals become involved in coalition operations and activities remains ambiguous. A grounded theory approach was used to explore expressions of participant involvement of a local health coalition known as the Active Living Coalition (ALC). Open, axial, as well as domain and taxonomic coding were used to analyze transcripts from four focus groups (n = 37 participants) in order to develop a participant continuum that captured six network aggregates within the coalition. Findings suggest that participation, for the most part, was heterogeneous and ever-changing given the expectations of the level of partnership that best individuals' personal and professional interests. Differentiating the type of participants in health coalitions can help coalition leaders more successfully "manage" new and existing relationships. Findings imply that health coalitions can maximize coalition capacity by drawing upon the full range of potential human and material resources by further understanding the types of individuals that make up their network. PMID:25812479

  11. Involvement of a phospholipase C in the hemolytic activity of a clinical strain of Pseudomonas fluorescens

    PubMed Central

    Rossignol, Gaelle; Merieau, Annabelle; Guerillon, Josette; Veron, Wilfried; Lesouhaitier, Olivier; Feuilloley, Marc GJ; Orange, Nicole

    2008-01-01

    Background Pseudomonas fluorescens is a ubiquitous Gram-negative bacterium frequently encountered in hospitals as a contaminant of injectable material and surfaces. This psychrotrophic bacterium, commonly described as unable to grow at temperatures above 32°C, is now considered non pathogenic. We studied a recently identified clinical strain of P. fluorescens biovar I, MFN1032, which is considered to cause human lung infection and can grow at 37°C in laboratory conditions. Results We found that MFN1032 secreted extracellular factors with a lytic potential at least as high as that of MF37, a psychrotrophic strain of P. fluorescens or the mesophilic opportunistic pathogen, Pseudomonas aeruginosa PAO1. We demonstrated the direct, and indirect – through increases in biosurfactant release – involvement of a phospholipase C in the hemolytic activity of this bacterium. Sequence analysis assigned this phospholipase C to a new group of phospholipases C different from those produced by P. aeruginosa. We show that changes in PlcC production have pleiotropic effects and that plcC overexpression and plcC extinction increase MFN1032 toxicity and colonization, respectively. Conclusion This study provides the first demonstration that a PLC is involved in the secreted hemolytic activity of a clinical strain of Pseudomonas fluorescens. Moreover, this phospholipase C seems to belong to a complex biological network associated with the biosurfactant production. PMID:18973676

  12. Caveolin-1 is involved in reactive oxygen species-induced SHP-2 activation in astrocytes

    PubMed Central

    Yun, Ji Hee; Park, Soo Jung; Jo, Ara; Jou, Ilo; Park, Jung Soo

    2011-01-01

    Recent evidence supports a neuroprotective role of Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2) against ischemic brain injury. However, the molecular mechanisms of SHP-2 activation and those governing how SHP-2 exerts its function under oxidative stress conditions are not well understood. Recently we have reported that reactive oxygen species (ROS)-mediated oxidative stress promotes the phosphorylation of endogenous SHP-2 through lipid rafts, and that this phosphorylation strongly occurs in astrocytes, but not in microglia. To investigate the molecules involved in events leading to phosphorylation of SHP-2, raft proteins were analyzed using astrocytes and microglia. Interestingly, caveolin-1 and -2 were detected only in astrocytes but not in microglia, whereas flotillin-1 was expressed in both cell types. To examine whether the H2O2-dependent phosphorylation of SHP-2 is mediated by caveolin-1, we used specific small interfering RNA (siRNA) to downregulate caveolin-1 expression. In the presence of caveolin-1 siRNA, the level of SHP-2 phosphorylation induced by H2O2 was significantly decreased, compared with in the presence of control siRNA. Overexpression of caveolin-1 effectively increased H2O2-induced SHP-2 phosphorylation in microglia. Lastly, H2O2 induced extracellular signal-regulated kinase (ERK) activation in astrocytes through caveolin-1. Our results suggest that caveolin-1 is involved in astrocyte-specific intracellular responses linked to the SHP-2-mediated signaling cascade following ROS-induced oxidative stress. PMID:21918362

  13. Developmental changes in brain activation involved in the production of novel speech sounds in children.

    PubMed

    Hashizume, Hiroshi; Taki, Yasuyuki; Sassa, Yuko; Thyreau, Benjamin; Asano, Michiko; Asano, Kohei; Takeuchi, Hikaru; Nouchi, Rui; Kotozaki, Yuka; Jeong, Hyeonjeong; Sugiura, Motoaki; Kawashima, Ryuta

    2014-08-01

    Older children are more successful at producing unfamiliar, non-native speech sounds than younger children during the initial stages of learning. To reveal the neuronal underpinning of the age-related increase in the accuracy of non-native speech production, we examined the developmental changes in activation involved in the production of novel speech sounds using functional magnetic resonance imaging. Healthy right-handed children (aged 6-18 years) were scanned while performing an overt repetition task and a perceptual task involving aurally presented non-native and native syllables. Productions of non-native speech sounds were recorded and evaluated by native speakers. The mouth regions in the bilateral primary sensorimotor areas were activated more significantly during the repetition task relative to the perceptual task. The hemodynamic response in the left inferior frontal gyrus pars opercularis (IFG pOp) specific to non-native speech sound production (defined by prior hypothesis) increased with age. Additionally, the accuracy of non-native speech sound production increased with age. These results provide the first evidence of developmental changes in the neural processes underlying the production of novel speech sounds. Our data further suggest that the recruitment of the left IFG pOp during the production of novel speech sounds was possibly enhanced due to the maturation of the neuronal circuits needed for speech motor planning. This, in turn, would lead to improvement in the ability to immediately imitate non-native speech. PMID:24585739

  14. CIPK23 is involved in iron acquisition of Arabidopsis by affecting ferric chelate reductase activity.

    PubMed

    Tian, Qiuying; Zhang, Xinxin; Yang, An; Wang, Tianzuo; Zhang, Wen-Hao

    2016-05-01

    Iron deficiency is one of the major limiting factors affecting quality and production of crops in calcareous soils. Numerous signaling molecules and transcription factors have been demonstrated to play a regulatory role in adaptation of plants to iron deficiency. However, the mechanisms underlying the iron deficiency-induced physiological processes remain to be fully dissected. Here, we demonstrated that the protein kinase CIPK23 was involved in iron acquisition. Lesion of CIPK23 rendered Arabidopsis mutants hypersensitive to iron deficiency, as evidenced by stronger chlorosis in young leaves and lower iron concentration than wild-type plants under iron-deficient conditions by down-regulating ferric chelate reductase activity. We found that iron deficiency evoked an increase in cytosolic Ca(2+) concentration and the elevated Ca(2+) would bind to CBL1/CBL9, leading to activation of CIPK23. These novel findings highlight the involvement of calcium-dependent CBL-CIPK23 complexes in the regulation of iron acquisition. Moreover, mutation of CIPK23 led to changes in contents of mineral elements, suggesting that CBL-CIPK23 complexes could be as "nutritional sensors" to sense and regulate the mineral homeostasis in Arabisopsis. PMID:26993237

  15. An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome)

    PubMed Central

    Esmaili, Haydarali; Mostafidi, Elmira; Mehramuz, Bahareh; Ardalan, Mohammadreza; Mohajel-Shoja, Mohammadali

    2016-01-01

    Context: Hemophagocytic syndrome (HPS) is mainly characterized by massive infiltration of bone marrow by activated macrophages and often presents with pancytopenia. Thrombotic microangiopathy (TMA) is also present with thrombocytopenia and renal involvement. Both conditions could coexist with each other and complicate the condition. Evidence Acquisition: Directory of Open Access Journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science with keywords relevant to; Hemophagocytic syndrome, macrophage activation syndrome, interferon-gamma and thrombotic microangiopathy, have been searched. Results: Viral infection, rheumatologic disease and malignancies are the main underlying causes for secondary HPS. calcineurin inhibitors and viral infections are also the main underlying causes of TMA in transplant recipients. In this review, we discussed a 39-year-old male who presented with pancytopenia and renal allograft dysfunction. With the diagnosis of HPS induced TMA his renal condition and pancytopenia improved after receiving intravenous immunoglobulin (IVIG) and plasmapheresis therapy. Conclusions: HPS is an increasingly recognized disorder in the realm of different medical specialties. Renal involvement complicates the clinical picture of the disease, and this condition even is more complex in renal transplant recipients. We should consider the possibility of HPS in any renal transplant recipient with pancytopenia and allograft dysfunction. The combination of HPS with TMA future increases the complexity of the situation. PMID:27047804

  16. Shrinkage activates a nonselective conductance: involvement of a Walker-motif protein and PKC.

    PubMed

    Nelson, D J; Tien, X Y; Xie, W; Brasitus, T A; Kaetzel, M A; Dedman, J R

    1996-01-01

    The ability of all cells to maintain their volume during an osmotic challenge is dependent on the regulated movement of salt and water across the plasma membrane. We demonstrate the phosphorylation-dependent gating of a nonselective conductance in Caco-2 cells during cellular shrinkage. Intracellular application of exogenous purified rat brain protein kinase C (PKC) resulted in the activation of a current similar to that activated during shrinkage with a Na(+)-to-Cl- permeability ratio of approximately 1.7:1. To prevent possible PKC- and/or shrinkage-dependent activation of cystic fibrosis transmembrane regulator (CFTR), which is expressed at high levels in Caco-2 cells, a functional anti-peptide antibody, anti-CFTR505-511, was introduced into the cells via the patch pipette. Anti-CFTR505-511, which is directed against the Walker motif in the first nucleotide binding fold of CFTR, prevented the PKC/shrink-age current activation. The peptide CFTR505-511 also induced current inhibition, suggesting the possible involvement of a regulatory element in close proximity to the channel that shares sequence homology with the first nucleotide binding fold of CFTR and whose binding to the channel is required for channel gating. PMID:8772443

  17. Young People's Views on Accelerometer Use in Physical Activity Research: Findings from a User Involvement Investigation.

    PubMed

    Kirby, Joanna; Tibbins, Carly; Callens, Claire; Lang, Beckie; Thorogood, Margaret; Tigbe, William; Robertson, Wendy

    2012-01-01

    The use of accelerometers to objectively measure physical activity is important in understanding young people's behaviours, as physical activity plays a key part in obesity prevention and treatment. A user-involvement qualitative study with young people aged 7-18 years (n = 35) was carried out to investigate views on accelerometer use to inform an obesity treatment research study. First impressions were often negative, with issues related to size and comfort reported. Unwanted attention from wearing an accelerometer and bullying risk were also noted. Other disadvantages included feeling embarrassed and not being able to wear the device for certain activities. Positive aspects included feeling "special" and having increased attention from friends. Views on the best time to wear accelerometers were mixed. Advice was offered on how to make accelerometers more appealing, including presenting them in a positive way, using a clip rather than elastic belt to attach, personalising the device, and having feedback on activity levels. Judgements over the way in which accelerometers are used should be made at the study development stage and based on the individual population. In particular, introducing accelerometers in a clear and positive way is important. Including a trial wearing period, considering practical issues, and providing incentives may help increase compliance. PMID:24533214

  18. Effects of negative air ions on activity of neural substrates involved in autonomic regulation in rats

    NASA Astrophysics Data System (ADS)

    Suzuki, Satoko; Yanagita, Shinya; Amemiya, Seiichiro; Kato, Yumi; Kubota, Natsuko; Ryushi, Tomoo; Kita, Ichiro

    2008-07-01

    The neural mechanism by which negative air ions (NAI) mediate the regulation of autonomic nervous system activity is still unknown. We examined the effects of NAI on physiological responses, such as blood pressure (BP), heart rate (HR), and heart rate variability (HRV) as well as neuronal activity, in the paraventricular nucleus of the hypothalamus (PVN), locus coeruleus (LC), nucleus ambiguus (NA), and nucleus of the solitary tract (NTS) with c-Fos immunohistochemistry in anesthetized, spontaneously breathing rats. In addition, we performed cervical vagotomy to reveal the afferent pathway involved in mediating the effects of NAI on autonomic regulation. NAI significantly decreased BP and HR, and increased HF power of the HRV spectrum. Significant decreases in c-Fos positive nuclei in the PVN and LC, and enhancement of c-Fos expression in the NA and NTS were induced by NAI. After vagotomy, these physiological and neuronal responses to NAI were not observed. These findings suggest that NAI can modulate autonomic regulation through inhibition of neuronal activity in PVN and LC as well as activation of NA neurons, and that these effects of NAI might be mediated via the vagus nerves.

  19. Mitochondrial Dysfunction Is Involved in the Toxic Activity of Boric Acid against Saprolegnia

    PubMed Central

    Ali, Shimaa E.; Thoen, Even; Evensen, Øystein; Wiik-Nielsen, Jannicke; Gamil, Amr A. A.; Skaar, Ida

    2014-01-01

    There has been a significant increase in the incidence of Saprolegnia infections over the past decades, especially after the banning of malachite green. Very often these infections are associated with high economic losses in salmonid farms and hatcheries. The use of boric acid to control the disease has been investigated recently both under in vitro and in vivo conditions, however its possible mode of action against fish pathogenic Saprolegnia is not known. In this study, we have explored the transformation in Saprolegnia spores/hyphae after exposure to boric acid (1 g/L) over a period 4–24 h post treatment. Using transmission electron microscopy (TEM), early changes in Saprolegnia spores were detected. Mitochondrial degeneration was the most obvious sign observed following 4 h treatment in about 20% of randomly selected spores. We also investigated the effect of the treatment on nuclear division, mitochondrial activity and function using confocal laser scanning microscopy (CLSM). Fluorescence microscopy was also used to test the effect of treatment on mitochondrial membrane potential and formation of reactive oxygen species. Additionally, the viability and proliferation of treated spores that correlated to mitochondrial enzymatic activity were tested using an MTS assay. All obtained data pointed towards changes in the mitochondrial structure, membrane potential and enzymatic activity following treatment. We have found that boric acid has no effect on the integrity of membranes of Saprolegnia spores at concentrations tested. It is therefore likely that mitochondrial dysfunction is involved in the toxic activity of boric acid against Saprolegnia spp. PMID:25354209

  20. Afferent Arteriolar Dilation to 11,12-EET Analogs Involves PP2A Activity and Ca2+-Activated K+ Channels

    PubMed Central

    Imig, John D.; Dimitropoulou, Christiana; Reddy, D. Sudarshan; White, Richard E.; Falck, John R.

    2008-01-01

    The epoxygenase metabolite, 11,12-epoxyeicosatrienoic acid (11,12-EET), has renal vascular actions. 11,12-EET analogs have been developed to determine the structure activity relationship for 11,12-EET and as a tool to investigate signaling mechanisms responsible for afferent arteriolar dilation. We hypothesized that 11,12-EET mediated afferent arteriolar dilation involves increased phosphoprotein phosphatase 2A (PP2A) and large-conductance calcium activated K+ (KCa) channels. We evaluated the chemically and/or metabolically stable 11,12-EET analogs: 11,12-EET-N-methylsulfonimide (11,12-EET-SI), 11-nonyloxy-undec-8(Z)-enoic acid (11,12-ether-EET-8-ZE), and 11,12-trans-oxidoeicosa-8(Z)-eonoic acid (11,12-tetra-EET-8-ZE). Afferent arteriolar responses were assessed. Activation of KCa channels by 11,12-EET analogs were established by single cell channel recordings in renal myocytes. Assessment of renal vascular responses revealed that 11,12-EET analogs increased afferent arteriolar diameter. Vasodilator responses to 11,12-EET analogs were abolished by K+ channel or PP2A inhibition. 11,12-EET analogs activated renal myocyte large-conductance KCa channels. 11,12-EET analogs increased cAMP by 2-fold and PP2A activity increased 3-8 fold in renal myocytes. PP2A inhibition did not significantly affect the 11,12-EET analog mediated increase in cAMP and PP2A increased renal myocyte KCa channel activity to a much greater extent than PKA. These data support the concept that 11,12-EET utilizes PP2A dependent pathways to activate large-conductance KCa channels and dilate the afferent arteriole. PMID:18260004

  1. Automated Scheduling of Personnel to Staff Operations for the Mars Science Laboratory

    NASA Technical Reports Server (NTRS)

    Knight, Russell; Mishkin, Andrew; Allbaugh, Alicia

    2014-01-01

    Leveraging previous work on scheduling personnel for space mission operations, we have adapted ASPEN (Activity Scheduling and Planning Environment) [1] to the domain of scheduling personnel for operations of the Mars Science Laboratory. Automated scheduling of personnel is not new. We compare our representations to a sampling of employee scheduling systems available with respect to desired features. We described the constraints required by MSL personnel schedulers and how each is handled by the scheduling algorithm.

  2. Joint Associations of Residential Density and Neighborhood Involvement with Physical Activity among a Multiethnic Sample of Urban Adults

    ERIC Educational Resources Information Center

    Johnson-Lawrence, Vicki; Schulz, Amy J.; Zenk, Shannon N.; Israel, Barbara A.; Wineman, Jean; Marans, Robert W.; Rowe, Zachary

    2015-01-01

    Regular physical activity is associated with improvements in overall health. Although resident involvement in neighborhood social activities is positively associated with physical activity, neighborhood design features, including residential density, have varied associations with physical activity. Using data from a multiethnic sample of 696…

  3. Vimentin Is Involved in Peptidylarginine Deiminase 2-Induced Apoptosis of Activated Jurkat Cells

    PubMed Central

    Hsu, Pei-Chen; Liao, Ya-Fan; Lin, Chin-Li; Lin, Wen-Hao; Liu, Guang-Yaw; Hung, Hui-Chih

    2014-01-01

    Peptidylarginine deiminase type 2 (PADI2) deiminates (or citrullinates) arginine residues in protein to citrulline residues in a Ca2+-dependent manner, and is found in lymphocytes and macrophages. Vimentin is an intermediate filament protein and a well-known substrate of PADI2. Citrullinated vimentin is found in ionomycin-induced macrophage apoptosis. Citrullinated vimentin is the target of anti-Sa antibodies, which are specific to rheumatoid arthritis, and play a critical role in the pathogenesis of the disease. To investigate the role of PADI2 in apoptosis, we generated a Jurkat cell line that overexpressed the PADI2 transgene from a tetracycline-inducible promoter, and used a combination of 12-O-tetradecanoylphorbol-13-acetate and ionomycin to activate Jurkat cells. We found that PADI2 overexpression reduced the cell viability of activated Jurkat cells in a dose- and time-dependent manner. The PADI2-overexpressed and -activated Jurkat cells presented typical manifestations of apoptosis, and exhibited greater levels of citrullinated proteins, including citrullinated vimentin. Vimentin overexpression rescued a portion of the cells from apoptosis. In conclusion, PADI2 overexpression induces apoptosis in activated Jurkat cells. Vimentin is involved in PADI2-induced apoptosis. Moreover, PADI2-overexpressed Jurkat cells secreted greater levels of vimentin after activation, and expressed more vimentin on their cell surfaces when undergoing apoptosis. Through artificially highlighting PADI2 and vimentin, we demonstrated that PADI2 and vimentin participate in the apoptotic mechanisms of activated T lymphocytes. The secretion and surface expression of vimentin are possible ways of autoantigen presentation to the immune system. PMID:24850148

  4. Mutational Analysis of Cvab, an ABC Transporter Involved in the Secretion of Active Colicin V

    PubMed Central

    Tai, Phang C.

    2012-01-01

    CvaB is the central membrane transporter of the colicin V secretion system that belongs to an ATP-binding cassette superfamily. Previous data showed that the N-terminal and C-terminal domains of CvaB are essential for the function of CvaB. N-terminal domain of CvaB possesses Ca2+-dependent cysteine proteolytic activity, and two critical residues, Cys32 and His105, have been identified. In this study, we also identify Asp121 as being the third residue of the putative catalytic triad within the active site of the enzyme. The Asp121 mutants lose both their colicin V secretion activity and N-terminal proteolytic activity. The adjacent residue Pro122 also appears to play a critical role in the colicin V secretion. However, the reversal of the two residues D121P - P122D results in loss of activity. Based on molecular modeling and protein sequence alignment, several residues adjacent to the critical residues, Cys32 and His105, were also examined and characterized. Site-directed mutagenesis of Trp101, Asp102, Val108, Leu76, Gly77, and Gln26 indicate that the neighboring residues around the catalytic triad affect colicin V secretion. Several mutated CvaB proteins with defective secretion were also tested, including Asp121 and Pro122, and were found to be structurally stable. These results indicate that the residues surrounding the identified catalytic triad are functionally involved in the secretion of biologically active colicin V. PMID:22539970

  5. 39 CFR 3010.7 - Schedule of regular rate changes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... mailers to predict with reasonable accuracy the amounts of future scheduled rate changes. (d) The initial... explanation is required for changes involving smaller than predicted rate adjustments....

  6. AVLIS production plant project schedule and milestones

    SciTech Connect

    Not Available

    1984-11-15

    An AVLIS Production Plant Deployment Schedule for the engineering, procurement, and construction for both the Initial Increment of Production and the fully Activated Plant, has been developed by the project team consisting of Lawrence Livermore National Laboratory, Martin Marietta Energy Systems, Inc. with architect-engineer support from Bechtel National, Inc., Stone and Webster Engineering Corporation, and Westinghouse Corporation. The initial deployment phase consists of six separators modules and the three laser power amplifier modules consistent with the FY84 reference design with a name plate capacity of 5 million separative work units/yr followed by a full plant activation to approximately 13 million separative work units/yr. The AVLIS Production Plant project team's strategy for deployment schedule analysis focused on three schedule options: engineering limited schedule; authorization limited schedule; and funding limited project schedule. The three deployment schedule options developed by AVLIS project team have been classified in ranges such as an optimistic, rapid/moderate, or moderate/pessimistic based on the probability of meeting the individual schedule option's major milestones or program objectives of enriching uranium by the AVLIS process in an effective cost and schedule manner. 47 figures, 7 tables.

  7. Aβ and NMDAR activation cause mitochondrial dysfunction involving ER calcium release.

    PubMed

    Ferreira, Ildete Luísa; Ferreiro, Elisabete; Schmidt, Jeannette; Cardoso, João M; Pereira, Cláudia M F; Carvalho, Ana Luísa; Oliveira, Catarina R; Rego, A Cristina

    2015-02-01

    Early cognitive deficits in Alzheimer's disease (AD) seem to be correlated to dysregulation of glutamate receptors evoked by amyloid-beta (Aβ) peptide. Aβ interference with the activity of N-methyl-d-aspartate receptors (NMDARs) may be a relevant factor for Aβ-induced mitochondrial toxicity and neuronal dysfunction. To evaluate the role of mitochondria in NMDARs activation mediated by Aβ, we followed in situ single-cell simultaneous measurement of cytosolic free Ca(2+)(Cai(2+)) and mitochondrial membrane potential in primary cortical neurons. Our results show that direct exposure to Aβ + NMDA largely increased Cai(2+) and induced immediate mitochondrial depolarization, compared with Aβ or NMDA alone. Mitochondrial depolarization induced by rotenone strongly inhibited the rise in Cai(2+) evoked by Aβ or NMDA, suggesting that mitochondria control Ca(2+) entry through NMDARs. However, incubation with rotenone did not preclude mitochondrial Ca(2+) (mitCa(2+)) retention in cells treated with Aβ. Aβ-induced Cai(2+) and mitCa(2+) rise were inhibited by ifenprodil, an antagonist of GluN2B-containing NMDARs. Exposure to Aβ + NMDA further evoked a higher mitCa(2+) retention, which was ameliorated in GluN2B(-/-) cortical neurons, largely implicating the involvement of this NMDAR subunit. Moreover, pharmacologic inhibition of endoplasmic reticulum (ER) inositol-1,4,5-triphosphate receptor (IP3R) and mitCa(2+) uniporter (MCU) evidenced that Aβ + NMDA-induced mitCa(2+) rise involves ER Ca(2+) release through IP3R and mitochondrial entry by the MCU. Altogether, data highlight mitCa(2+) dyshomeostasis and subsequent dysfunction as mechanisms relevant for early neuronal dysfunction in AD linked to Aβ-mediated GluN2B-composed NMDARs activation. PMID:25442114

  8. Iterative modulo scheduling

    SciTech Connect

    Rau, B.R.

    1996-02-01

    Modulo scheduling is a framework within which algorithms for software pipelining innermost loops may be defined. The framework specifies a set of constraints that must be met in order to achieve a legal modulo schedule. A wide variety of algorithms and heuristics can be defined within this framework. Little work has been done to evaluate and compare alternative algorithms and heuristics for modulo scheduling from the viewpoints of schedule quality as well as computational complexity. This, along with a vague and unfounded perception that modulo scheduling is computationally expensive as well as difficult to implement, have inhibited its corporation into product compilers. This paper presents iterative modulo scheduling, a practical algorithm that is capable of dealing with realistic machine models. The paper also characterizes the algorithm in terms of the quality of the generated schedules as well as the computational incurred.

  9. Determination of Dehydrogenase Activities Involved in D-Glucose Oxidation in Gluconobacter and Acetobacter Strains

    PubMed Central

    Sainz, Florencia; Jesús Torija, María; Matsutani, Minenosuke; Kataoka, Naoya; Yakushi, Toshiharu; Matsushita, Kazunobu; Mas, Albert

    2016-01-01

    Acetic acid bacteria (AAB) are known for rapid and incomplete oxidation of an extensively variety of alcohols and carbohydrates, resulting in the accumulation of organic acids as the final products. These oxidative fermentations in AAB are catalyzed by PQQ- or FAD- dependent membrane-bound dehydrogenases. In the present study, the enzyme activity of the membrane-bound dehydrogenases [membrane-bound PQQ-glucose dehydrogenase (mGDH), D-gluconate dehydrogenase (GADH) and membrane-bound glycerol dehydrogenase (GLDH)] involved in the oxidation of D-glucose and D-gluconic acid (GA) was determined in six strains of three different species of AAB (three natural and three type strains). Moreover, the effect of these activities on the production of related metabolites [GA, 2-keto-D-gluconic acid (2KGA) and 5-keto-D-gluconic acid (5KGA)] was analyzed. The natural strains belonging to Gluconobacter showed a high mGDH activity and low activity in GADH and GLDH, whereas the Acetobacter malorum strain presented low activity in the three enzymes. Nevertheless, no correlation was observed between the activity of these enzymes and the concentration of the corresponding metabolites. In fact, all the tested strains were able to oxidize D-glucose to GA, being maximal at the late exponential phase of the AAB growth (24 h), which coincided with D-glucose exhaustion and the maximum mGDH activity. Instead, only some of the tested strains were capable of producing 2KGA and/or 5KGA. In the case of Gluconobacter oxydans strains, no 2KGA production was detected which is related to the absence of GADH activity after 24 h, while in the remaining strains, detection of GADH activity after 24 h resulted in a high accumulation of 2KGA. Therefore, it is possible to choose the best strain depending on the desired product composition. Moreover, the sequences of these genes were used to construct phylogenetic trees. According to the sequence of gcd, gene coding for mGDH, Acetobacter and Komagataeibacter

  10. Determination of Dehydrogenase Activities Involved in D-Glucose Oxidation in Gluconobacter and Acetobacter Strains.

    PubMed

    Sainz, Florencia; Jesús Torija, María; Matsutani, Minenosuke; Kataoka, Naoya; Yakushi, Toshiharu; Matsushita, Kazunobu; Mas, Albert

    2016-01-01

    Acetic acid bacteria (AAB) are known for rapid and incomplete oxidation of an extensively variety of alcohols and carbohydrates, resulting in the accumulation of organic acids as the final products. These oxidative fermentations in AAB are catalyzed by PQQ- or FAD- dependent membrane-bound dehydrogenases. In the present study, the enzyme activity of the membrane-bound dehydrogenases [membrane-bound PQQ-glucose dehydrogenase (mGDH), D-gluconate dehydrogenase (GADH) and membrane-bound glycerol dehydrogenase (GLDH)] involved in the oxidation of D-glucose and D-gluconic acid (GA) was determined in six strains of three different species of AAB (three natural and three type strains). Moreover, the effect of these activities on the production of related metabolites [GA, 2-keto-D-gluconic acid (2KGA) and 5-keto-D-gluconic acid (5KGA)] was analyzed. The natural strains belonging to Gluconobacter showed a high mGDH activity and low activity in GADH and GLDH, whereas the Acetobacter malorum strain presented low activity in the three enzymes. Nevertheless, no correlation was observed between the activity of these enzymes and the concentration of the corresponding metabolites. In fact, all the tested strains were able to oxidize D-glucose to GA, being maximal at the late exponential phase of the AAB growth (24 h), which coincided with D-glucose exhaustion and the maximum mGDH activity. Instead, only some of the tested strains were capable of producing 2KGA and/or 5KGA. In the case of Gluconobacter oxydans strains, no 2KGA production was detected which is related to the absence of GADH activity after 24 h, while in the remaining strains, detection of GADH activity after 24 h resulted in a high accumulation of 2KGA. Therefore, it is possible to choose the best strain depending on the desired product composition. Moreover, the sequences of these genes were used to construct phylogenetic trees. According to the sequence of gcd, gene coding for mGDH, Acetobacter and Komagataeibacter

  11. Bakuchiol Is a Phenolic Isoprenoid with Novel Enantiomer-selective Anti-influenza A Virus Activity Involving Nrf2 Activation*

    PubMed Central

    Shoji, Masaki; Arakaki, Yumie; Esumi, Tomoyuki; Kohnomi, Shuntaro; Yamamoto, Chihiro; Suzuki, Yutaka; Takahashi, Etsuhisa; Konishi, Shiro; Kido, Hiroshi; Kuzuhara, Takashi

    2015-01-01

    Influenza represents a substantial threat to human health and requires novel therapeutic approaches. Bakuchiol is a phenolic isoprenoid compound present in Babchi (Psoralea corylifolia L.) seeds. We examined the anti-influenza viral activity of synthetic bakuchiol using Madin-Darby canine kidney cells. We found that the naturally occurring form, (+)-(S)-bakuchiol, and its enantiomer, (−)-(R)-bakuchiol, inhibited influenza A viral infection and growth and reduced the expression of viral mRNAs and proteins in these cells. Furthermore, these compounds markedly reduced the mRNA expression of the host cell influenza A virus-induced immune response genes, interferon-β and myxovirus-resistant protein 1. Interestingly, (+)-(S)-bakuchiol had greater efficacy than (−)-(R)-bakuchiol, indicating that chirality influenced anti-influenza virus activity. In vitro studies indicated that bakuchiol did not strongly inhibit the activities of influenza surface proteins or the M2 ion channel, expressed in Chinese hamster ovary cells. Analysis of luciferase reporter assay data unexpectedly indicated that bakuchiol may induce some host cell factor(s) that inhibited firefly and Renilla luciferases. Next generation sequencing and KeyMolnet analysis of influenza A virus-infected and non-infected cells exposed to bakuchiol revealed activation of transcriptional regulation by nuclear factor erythroid 2-related factor (Nrf), and an Nrf2 reporter assay showed that (+)-(S)-bakuchiol activated Nrf2. Additionally, (+)-(S)-bakuchiol up-regulated the mRNA levels of two Nrf2-induced genes, NAD(P)H quinone oxidoreductase 1 and glutathione S-transferase A3. These findings demonstrated that bakuchiol had enantiomer-selective anti-influenza viral activity involving a novel effect on the host cell oxidative stress response. PMID:26446794

  12. Molecular Genetic Analysis of Activation-tagged Transcription Factors Thought to be Involved in Photomorphogenesis

    SciTech Connect

    Neff, Michael

    2011-06-23

    Plants utilize light as a source of information via families of photoreceptors such as the red/far-red absorbing phytochromes (PHY) and the blue/UVA absorbing cryptochromes (CRY). The main goal of the Neff lab is to use molecular-genetic mutant screens to elucidate signaling components downstream of these photoreceptors. Activation-tagging mutagenesis led to the identification of two putative transcription factors that may be involved in both photomorphogenesis and hormone signaling pathways. sob1-D (suppressor of phyB-dominant) mutant phenotypes are caused by the over-expression of a Dof transcription factor previously named OBP3. Our previous studies indicate that OBP3 is a negative regulator of light-mediated cotyledon expansion and may be involved in modulating responsiveness to the growth-regulating hormone auxin. The sob2-D mutant uncovers a role for LEP, a putative AP2/EREBP-like transcription factor, in seed germination, hypocotyl elongation and responsiveness to the hormone abscisic acid. Based on photobiological and genetic analysis of OBP3-knockdown and LEP-null mutations, we hypothesize that these transcription factors are involved in both light-mediated seedling development and hormone signaling. To examine the role that these genes play in photomorphogenesis we will: 1) Further explore the genetic role of OBP3 in cotyledon/leaf expansion and other photomorphogenic processes as well as examine potential physical interactions between OBP3 and CRY1 or other signaling components that genetically interact with this transcription factor 2) Test the hypothesis that OBP3 is genetically involved in auxin signaling and root development as well as examine the affects of this hormone and light on OBP3 protein accumulation. 3) Test the hypothesis that LEP is involved in seed germination, seedling photomorphogenesis and hormone signaling. Together these experiments will lead to a greater understanding of the complexity of interactions between photoreceptors and DNA

  13. Improving the active involvement of stakeholders and the public in flood risk management - tools of an involvement strategy and case study results from Austria, Germany and Italy

    NASA Astrophysics Data System (ADS)

    Fleischhauer, M.; Greiving, S.; Flex, F.; Scheibel, M.; Stickler, T.; Sereinig, N.; Koboltschnig, G.; Malvati, P.; Vitale, V.; Grifoni, P.; Firus, K.

    2012-09-01

    The EU Flood Risk Management Directive 2007/60/EC aims at an active involvement of interested parties in the setting up of flood risk management plans and thus calls for more governance-related decision-making. This requirement has two perspectives. On the one hand, there is (1) the question of how decision-makers can improve the quality of their governance process. On the other hand, there is (2) the question of how the public shall be appropriately informed and involved. These questions were the centre of the ERA-Net CRUE-funded project IMRA (integrative flood risk governance approach for improvement of risk awareness) that aimed at an optimisation of the flood risk management process by increasing procedural efficiency with an explicit involvement strategy. To reach this goal, the IMRA project partners developed two new approaches that were implemented in three case study areas for the first time in flood risk management: 1. risk governance assessment tool: An indicator-based benchmarking and monitoring tool was used to evaluate the performance of a flood risk management system in regard to ideal risk governance principles; 2. social milieu approach: The concept of social milieus was used to gain a picture of the people living in the case study regions to learn more about their lifestyles, attitudes and values and to use this knowledge to plan custom-made information and participation activities for the broad public. This paper presents basic elements and the application of two innovative approaches as a part of an "involvement strategy" that aims at the active involvement of all interested parties (stakeholders) for assessing, reviewing and updating flood risk management plans, as formulated in the EU Flood Risk Management Directive 2007/60/EC.

  14. Yarrowia lipolytica AAL genes are involved in peroxisomal fatty acid activation.

    PubMed

    Dulermo, Rémi; Gamboa-Meléndez, Heber; Ledesma-Amaro, Rodrigo; Thevenieau, France; Nicaud, Jean-Marc

    2016-07-01

    In yeast, β-oxidation of fatty acids (FAs) essentially takes place in peroxisomes, and FA activation must precede FA oxidation. In Saccharomyces cerevisiae, a single fatty-acyl–CoA-synthetase, ScFaa2p, mediates peroxisomal FA activation. We have previously shown that this reaction also exists in the oleaginous yeast Yarrowia lipolytica; however, the protein involved in this process remains unknown. Here, we found that proteins, named Aal proteins (Acyl/Aryl-CoA-ligases), resembling the 4-coumarate–CoA-ligase-like enzymes found in plants are involved in peroxisomal FA activation in Y. lipolytica; Y. lipolytica has 10 AAL genes, eight of which are upregulated by oleate. All the Aal proteins contain a PTS1-type peroxisomal targeting sequence (A/SKL), suggesting a peroxisomal localization. The function of the Aal proteins was analyzed using the faa1Δant1Δ mutant strain, which demonstrates neither cytoplasmic FA activation (direct result of FAA1 deletion) nor peroxisomal FA activation (indirect result of ANT1 deletion, a gene coding an ATP transporter). This strain is thus highly sensitive to external FA levels and unable to store external FAs in lipid bodies (LBs). Whereas the overexpression of (cytoplasmic) AAL1ΔPTS1 was able to partially complement the growth defect observed in the faa1Δant1Δ mutant on short-, medium- and long-chain FA media, the presence of Aal2p to Aal10p only allowed growth on the short-chain FA medium. Additionally, partial LB formation was observed in the oleate medium for strains overexpressing Aal1ΔPTS1p, Aal4ΔPTS1p, Aal7ΔPTS1p, and Aal8ΔPTS1p. Finally, an analysis of the FA content of cells grown in the oleate medium suggested that Aal4p and Aal6p present substrate specificity for C16:1 and/or C18:0. PMID:27067366

  15. atRA-induced apoptosis of mouse embryonic palate mesenchymal cells involves activation of MAPK pathway

    SciTech Connect

    Yu Zengli . E-mail: yuzengli@263.net; Xing Ying . E-mail: xingy@zzu.edu.cn

    2006-08-15

    Our previous studies have shown that atRA treatment resulted in cell-cycle block and growth inhibition in mouse embryonic palatal mesenchymal (MEPM). In the current study, gestation day (GD) 13 MEPM cells were used to test the hypothesis that the growth inhibition by atRA is due to apoptosis. The effects of atRA on apoptosis were assessed by performing MTT assay, Cell Death Detection ELISA and flow cytometry, respectively. Data analysis confirmed that atRA treatment induced apoptosis-like cell death, as shown by decreased cell viability and increased fragmented DNA and sub-G1 fraction. atRA-induced apoptosis was associated with upregulation of bcl-2, translocation of bax protein to the mitochondria from the cytosol, activation of caspase-3 and cytochrome c release into cytosol. atRA-induced apoptosis was abrogated by z-DEVD-fmk, a caspase-3 specific inhibitor, and z-VAD-fmk, a general caspase inhibitor, suggesting that the atRA-induced cell death of MEPM cells occurs through the cytochrome c- and caspase-3-dependent pathways. In addition, atRA treatment caused a strong and sustained activation of c-Jun N-terminal kinase (JNK) and p38 kinase (p38), as well as an early but transient activation of extracellular signal-regulated kinase (ERK). Importantly, atRA-induced DNA fragmentation and capase-3 activation were prevented by pretreatment with the JNK inhibitor (SP600125) and the p38 MAPK inhibitor (SB202190), but not by pretreatment with MEK inhibitor (U0126). From these results, we suggest that mitogen-activated protein kinase-dependent pathways is involved in the atRA-induced apoptosis of MEPM cells.

  16. I. Evidence that lymphotoxin activity involves both cytotoxic and stimulating factors.

    PubMed

    Ryzewska, A G; Darbrowska, B K

    1976-11-01

    This paper describes experiments undertaken to determine more uniform conditions for the generation of cytotoxic lymphokine--'lymphotoxin' (LT) in differently stimulated rat lymphocyte cultures, and to compare the sensitivity of different test systems for detecting rat LT activity in vitro. Wistar rat lymphoid cells were activated by culture with phytohaemagglutinin (PHA) and mixed lymphocyte cultures (MLC) with semi-allogeneic (Wistar x August) F1 lymphoid cells. Lymphocyte supernatants harvested between 1 and 8 days were tested for their effect on metabolism and viability of cultured mouse fibroblasts (L-929 cells) by four methods: (i) inhibition of [14C]leucine incorporation; (ii) total and viable cell counts in test tube cultures ('macro test'); (iii) viable cell counts in microtitre plates ('microtest'); and (iv) chromium (51Cr) release from chromated L-cell monolayers. Cytotoxic effects on target cells of lymphocyte supernatants were evident after 3 days of PHA stimulation and 6 days of mixed lymphocyte culture, and the most sensitive indication of cytotoxic activity provided by inhibition of amino-acid incorporation and by loss of viable L cells from monolayers in tube cultures. In dilutions greater than 1:16-1:32 both cytotoxic supernatants exhibited a stimulating effect on target-cell proliferation. Stimulation of L cells growth was also observed when monolayers were exposed for 24 h to 'early' (24 h) PHA undiluted supernatants. At a later time of exposure to these supernatants a considerable loss of total and viable cells in the monolayers was evident. The results indicated that both cytotoxic and growth-stimulating lymphokines could be generated during activation of rat lymphocytes. A hypothesis is suggested whereby 'lymphotoxin' activity in vitro arises from the sequential effects of stimulating and cytotoxic lymphokine, and whereby the balance of these effects in vivo might determine the response of fibroblasts involved in reactions of chronic allergic

  17. Influenza A Virus Panhandle Structure Is Directly Involved in RIG-I Activation and Interferon Induction

    PubMed Central

    Liu, GuanQun; Park, Hong-Su; Pyo, Hyun-Mi; Liu, Qiang

    2015-01-01

    ABSTRACT Retinoic acid-inducible gene I (RIG-I) is an important innate immune sensor that recognizes viral RNA in the cytoplasm. Its nonself recognition largely depends on the unique RNA structures imposed by viral RNA. The panhandle structure residing in the influenza A virus (IAV) genome, whose primary function is to serve as the viral promoter for transcription and replication, has been proposed to be a RIG-I agonist. However, this has never been proved experimentally. Here, we employed multiple approaches to determine if the IAV panhandle structure is directly involved in RIG-I activation and type I interferon (IFN) induction. First, in porcine alveolar macrophages, we demonstrated that the viral genomic coding region is dispensable for RIG-I-dependent IFN induction. Second, using in vitro-synthesized hairpin RNA, we showed that the IAV panhandle structure could directly bind to RIG-I and stimulate IFN production. Furthermore, we investigated the contributions of the wobble base pairs, mismatch, and unpaired nucleotides within the wild-type panhandle structure to RIG-I activation. Elimination of these destabilizing elements within the panhandle structure promoted RIG-I activation and IFN induction. Given the function of the panhandle structure as the viral promoter, we further monitored the promoter activity of these panhandle variants and found that viral replication was moderately affected, whereas viral transcription was impaired dramatically. In all, our results indicate that the IAV panhandle promoter region adopts a nucleotide composition that is optimal for balanced viral RNA synthesis and suboptimal for RIG-I activation. IMPORTANCE The IAV genomic panhandle structure has been proposed to be an RIG-I agonist due to its partial complementarity; however, this has not been experimentally confirmed. Here, we provide direct evidence that the IAV panhandle structure is competent in, and sufficient for, RIG-I activation and IFN induction. By constructing

  18. Flagellin-induced NADPH oxidase 4 activation is involved in atherosclerosis

    PubMed Central

    Kim, Jinoh; Seo, Misun; Kim, Su Kyung; Bae, Yun Soo

    2016-01-01

    It is widely accepted that bacterial infection-mediated inflammation facilitates development of atherosclerosis by activating toll-like receptor (TLR) signaling system. We reasoned that NADPH oxidases (Nox), required for TLR-mediated inflammatory response, are involved in atherogenesis. Here, we show that the activation of Nox4 through TLR5 regulates the inflammation of the endothelium and in atherogenesis. Flagellin-induced interaction between the COOH region of Nox4 and the TIR domain of TLR5 led to H2O2 generation, which in turn promoted the secretion of pro-inflammatory cytokines including IL-8, as well as the expression of ICAM-1 in human aortic endothelial cells (HAECs). Knockdown of the Nox4 in HAECs resulted in attenuated expressions of IL-8 and ICAM-1 leading to a reduction in the adhesion and trans-endothelial migration of monocytes. Challenge of recombinant FliC (rFliC) to the ApoE KO mice with high-fat diet (HFD) resulted in significantly increased atherosclerotic plaque sizes compared to the saline-injected mice. However, an injection of rFliC into the Nox4ApoE DKO mice with HFDs failed to generate atherosclerotic plaque, suggesting that Nox4 deficiency resulted in significant protections against rFliC-mediated atherogenesis. We conclude that TLR5-dependent Nox4 activation and subsequent H2O2 generation play critical roles for the development of atherosclerosis. PMID:27146088

  19. TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation

    PubMed Central

    Jouan-Lanhouet, S; Arshad, M I; Piquet-Pellorce, C; Martin-Chouly, C; Le Moigne-Muller, G; Van Herreweghe, F; Takahashi, N; Sergent, O; Lagadic-Gossmann, D; Vandenabeele, P; Samson, M; Dimanche-Boitrel, M-T

    2012-01-01

    Although TRAIL (tumor necrosis factor (TNF)-related apoptosis inducing ligand) is a well-known apoptosis inducer, we have previously demonstrated that acidic extracellular pH (pHe) switches TRAIL-induced apoptosis to regulated necrosis (or necroptosis) in human HT29 colon and HepG2 liver cancer cells. Here, we investigated the role of RIPK1 (receptor interacting protein kinase 1), RIPK3 and PARP-1 (poly (ADP-ribose) polymerase-1) in TRAIL-induced necroptosis in vitro and in concanavalin A (Con A)-induced murine hepatitis. Pretreatment of HT29 or HepG2 with pharmacological inhibitors of RIPK1 or PARP-1 (Nec-1 or PJ-34, respectively), or transient transfection with siRNAs against RIPK1 or RIPK3, inhibited both TRAIL-induced necroptosis and PARP-1-dependent intracellular ATP depletion demonstrating that RIPK1 and RIPK3 were involved upstream of PARP-1 activation and ATP depletion. In the mouse model of Con A-induced hepatitis, where death of mouse hepatocytes is dependent on TRAIL and NKT (Natural Killer T) cells, PARP-1 activity was positively correlated with liver injury and hepatitis was prevented both by Nec-1 or PJ-34. These data provide new insights into TRAIL-induced necroptosis with PARP-1 being active effector downstream of RIPK1/RIPK3 initiators and suggest that pharmacological inhibitors of RIPKs and PARP-1 could be new treatment options for immune-mediated hepatitis. PMID:22814620

  20. Astragaloside IV enhances diabetic wound healing involving upregulation of alternatively activated macrophages.

    PubMed

    Luo, Xiaochun; Huang, Ping; Yuan, Baohong; Liu, Tao; Lan, Fang; Lu, Xiaoyan; Dai, Liangcheng; Liu, Yunjun; Yin, Hui

    2016-06-01

    Astragaloside IV (AS-IV), one of the major active compounds extracted from Astragali Radix, has been used experimentally for its potent antiinflammatory and immunoregulatory activities. In this study, we further investigate the potential efficacy of AS-IV on impaired wound healing in streptozotocin-induced diabetic mice. A full-thickness skin wound was produced on the back of diabetic mice and treated with AS-IV or vehicle topically. Our results showed that AS-IV application promoted diabetic wound repair with wounds gaping narrower and exhibiting augmented reepithelialization. AS-IV enhanced the collagen deposition and the expression of extracellular matrix (ECM)-related genes such as fibronectin and collagen IIIa, which implies a direct effect of AS-IV on matrix synthesis. AS-IV also improved the new blood vessel formation in wound tissue with increased numbers of endothelial cells and enhanced expression of VEGF and vWF. Moreover, the beneficial effect of AS-IV was related to the development of polarized alternatively activated macrophages, which involved in resolution of inflammation and facilitation of wound repair. All together, these findings suggest that AS-IV may play a potential effect on maintenance of cutaneous homeostasis and acceleration of diabetic wound healing. PMID:27016716

  1. Flagellin-induced NADPH oxidase 4 activation is involved in atherosclerosis.

    PubMed

    Kim, Jinoh; Seo, Misun; Kim, Su Kyung; Bae, Yun Soo

    2016-01-01

    It is widely accepted that bacterial infection-mediated inflammation facilitates development of atherosclerosis by activating toll-like receptor (TLR) signaling system. We reasoned that NADPH oxidases (Nox), required for TLR-mediated inflammatory response, are involved in atherogenesis. Here, we show that the activation of Nox4 through TLR5 regulates the inflammation of the endothelium and in atherogenesis. Flagellin-induced interaction between the COOH region of Nox4 and the TIR domain of TLR5 led to H2O2 generation, which in turn promoted the secretion of pro-inflammatory cytokines including IL-8, as well as the expression of ICAM-1 in human aortic endothelial cells (HAECs). Knockdown of the Nox4 in HAECs resulted in attenuated expressions of IL-8 and ICAM-1 leading to a reduction in the adhesion and trans-endothelial migration of monocytes. Challenge of recombinant FliC (rFliC) to the ApoE KO mice with high-fat diet (HFD) resulted in significantly increased atherosclerotic plaque sizes compared to the saline-injected mice. However, an injection of rFliC into the Nox4ApoE DKO mice with HFDs failed to generate atherosclerotic plaque, suggesting that Nox4 deficiency resulted in significant protections against rFliC-mediated atherogenesis. We conclude that TLR5-dependent Nox4 activation and subsequent H2O2 generation play critical roles for the development of atherosclerosis. PMID:27146088

  2. Activation of PPAR{gamma} is not involved in butyrate-induced epithelial cell differentiation

    SciTech Connect

    Ulrich, S.; Waechtershaeuser, A.; Loitsch, S.; Knethen, A. von; Bruene, B.; Stein, J. . E-mail: j.stein@em.uni-frankfurt.de

    2005-10-15

    Histone deacetylase-inhibitors affect growth and differentiation of intestinal epithelial cells by inducing expression of several transcription factors, e.g. Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) or vitamin D receptor (VDR). While activation of VDR by butyrate mainly seems to be responsible for cellular differentiation, the activation of PPAR{gamma} in intestinal cells remains to be elucidated. The aim of this study was to determine the role of PPAR{gamma} in butyrate-induced cell growth inhibition and differentiation induction in Caco-2 cells. Treatment with PPAR{gamma} ligands ciglitazone and BADGE (bisphenol A diglycidyl) enhanced butyrate-induced cell growth inhibition in a dose- and time-dependent manner, whereas cell differentiation was unaffected after treatment with PPAR{gamma} ligands rosiglitazone and MCC-555. Experiments were further performed in dominant-negative PPAR{gamma} mutant cells leading to an increase in cell growth whereas butyrate-induced cell differentiation was again unaffected. The present study clearly demonstrated that PPAR{gamma} is involved in butyrate-induced inhibition of cell growth, but seems not to play an essential role in butyrate-induced cell differentiation.

  3. Transmembrane myosin chitin synthase involved in mollusc shell formation produced in Dictyostelium is active

    SciTech Connect

    Schoenitzer, Veronika; Eichner, Norbert; Clausen-Schaumann, Hauke; Weiss, Ingrid M.

    2011-12-02

    Highlights: Black-Right-Pointing-Pointer Dictyostelium produces the 264 kDa myosin chitin synthase of bivalve mollusc Atrina. Black-Right-Pointing-Pointer Chitin synthase activity releases chitin, partly associated with the cell surface. Black-Right-Pointing-Pointer Membrane extracts of transgenic slime molds produce radiolabeled chitin in vitro. Black-Right-Pointing-Pointer Chitin producing Dictyostelium cells can be characterized by atomic force microscopy. Black-Right-Pointing-Pointer This model system enables us to study initial processes of chitin biomineralization. -- Abstract: Several mollusc shells contain chitin, which is formed by a transmembrane myosin motor enzyme. This protein could be involved in sensing mechanical and structural changes of the forming, mineralizing extracellular matrix. Here we report the heterologous expression of the transmembrane myosin chitin synthase Ar-CS1 of the bivalve mollusc Atrina rigida (2286 amino acid residues, M.W. 264 kDa/monomer) in Dictyostelium discoideum, a model organism for myosin motor proteins. Confocal laser scanning immunofluorescence microscopy (CLSM), chitin binding GFP detection of chitin on cells and released to the cell culture medium, and a radiochemical activity assay of membrane extracts revealed expression and enzymatic activity of the mollusc chitin synthase in transgenic slime mold cells. First high-resolution atomic force microscopy (AFM) images of Ar-CS1 transformed cellulose synthase deficient D. discoideumdcsA{sup -} cell lines are shown.

  4. Regulation of retinoid mediated cholesterol efflux involves liver X receptor activation in mouse macrophages.

    PubMed

    Manna, Pulak R; Sennoune, Souad R; Martinez-Zaguilan, Raul; Slominski, Andrzej T; Pruitt, Kevin

    2015-08-14

    Removal of cholesterol from macrophage-derived foam cells is a critical step to the prevention of atherosclerotic lesions. We have recently demonstrated the functional importance of retinoids in the regulation of the steroidogenic acute regulatory (StAR) protein that predominantly mediates the intramitochondrial transport of cholesterol in target tissues. In the present study, treatment of mouse macrophages with retinoids, particularly all-trans retinoic acid (atRA) and 9-cis RA, resulted in increases in cholesterol efflux to apolipoprotein AI (Apo-A1). Activation of the PKA pathway by a cAMP analog, (Bu)2cAMP, markedly augmented retinoid mediated cholesterol efflux. Macrophages overexpressing hormone-sensitive lipase increased the hydrolysis of cholesteryl esters and concomitantly enhanced the efficacy of retinoic acid receptor and liver X receptor (LXR) ligands on StAR and ATP-binding cassette transporter A1 (ABCA1) protein levels. RAs elevated StAR promoter activity in macrophages, and an increase in StAR levels augmented cholesterol efflux to Apo-A1, suggesting retinoid-mediated efflux of cholesterol involves enhanced oxysterol production. Further studies revealed that retinoids activate the LXR regulated genes, sterol receptor-element binding protein-1c and ABCA1. These findings provide insights into the regulatory events in which retinoid signaling effectively enhances macrophage cholesterol efflux and indicate that retinoid therapy may have important implications in limiting and/or regressing atherosclerotic cardiovascular disease. PMID:26119689

  5. (-)-Linalool inhibits in vitro NO formation: Probable involvement in the antinociceptive activity of this monoterpene compound.

    PubMed

    Peana, Alessandra T; Marzocco, Stefania; Popolo, Ada; Pinto, Aldo

    2006-01-11

    Recent studies performed in our laboratory have shown that (-)-linalool, the natural occurring enantiomer in essential oils, possesses anti-inflammatory, antihyperalgesic and antinociceptive effects in different animal models. The antinociceptive and antihyperalgesic effect of (-)-linalool has been ascribed to the stimulation of the cholinergic, opioidergic and dopaminergic systems, to its local anaesthetic activity and to the blockade of N-Methyl-d-aspartate receptors (NMDA). Since nitric oxide (NO) and prostaglandin E(2) (PGE(2)) play an important role in oedema formation and hyperalgesia and nociception development, to investigate the mechanism of these actions of the (-)-linalool, we examined the effects of this compound on lipopolysaccharide (LPS)-induced responses in macrophage cell line J774.A1. Exposure of LPS-stimulated cells to (-)-linalool significantly inhibited nitrite accumulation in the culture medium without inhibiting the LPS-stimulated increase of inducible nitric oxide synthase (iNOS) expression, suggesting that the inhibitory activity of (-)-linalool is mainly due to the iNOS enzyme activity. In contrast, exposure of LPS-stimulated cells to (-)-linalool failed, if not at the highest concentration, both in inhibiting PGE(2) release and in inhibiting increase of inducible cyclooxygenase-2 (COX(2)) expression in the culture medium. Collectively, these results indicate that the reduction of NO production/release is responsible, at least partially, for the molecular mechanisms of (-)-linalool antinociceptive effect, probably through mechanisms where cholinergic and glutamatergic systems are involved. PMID:16137709

  6. A simple methodology to assess endolysosomal protease activity involved in antigen processing in human primary cells

    PubMed Central

    2013-01-01

    Background Endolysosomes play a key role in maintaining the homeostasis of the cell. They are made of a complex set of proteins that degrade lipids, proteins and sugars. Studies involving endolysosome contribution to cellular functions such as MHC class I and II epitope production have used recombinant endolysosomal proteins, knockout mice that lack one of the enzymes or purified organelles from human tissue. Each of these approaches has some caveats in analyzing endolysosomal enzyme functions. Results In this study, we have developed a simple methodology to assess endolysosomal protease activity. By varying the pH in crude lysate from human peripheral blood mononuclear cells (PBMCs), we documented increased endolysosomal cathepsin activity in acidic conditions. Using this new method, we showed that the degradation of HIV peptides in low pH extracts analyzed by mass spectrometry followed similar kinetics and degradation patterns as those performed with purified endolysosomes. Conclusion By using crude lysate in the place of purified organelles this method will be a quick and useful tool to assess endolysosomal protease activities in primary cells of limited availability. This quick method will especially be useful to screen peptide susceptibility to degradation in endolysosomal compartments for antigen processing studies, following which detailed analysis using purified organelles may be used to study specific peptides. PMID:23937268

  7. Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing.

    PubMed Central

    Saarialho-Kere, U K; Kovacs, S O; Pentland, A P; Olerud, J E; Welgus, H G; Parks, W C

    1993-01-01

    We reported that interstitial collagenase is produced by keratinocytes at the edge of ulcers in pyogenic granuloma, and in this report, we assessed if production of this metalloproteinase is a common feature of the epidermal response in a variety of wounds. In all samples of chronic ulcers, regardless of etiology, and in incision wounds, collagenase mRNA, localized by in situ hybridization, was prominently expressed by basal keratinocytes bordering the sites of active re-epithelialization indicating that collagenolytic activity is a characteristic response of the epidermis to wounding. No expression of mRNAs for 72- and 92-kD gelatinases or matrilysin was seen in keratinocytes, and no signal for any metalloproteinase was detected in normal epidermis. Immunostaining for type IV collagen showed that collagenase-positive keratinocytes were not in contact with an intact basement membrane and, unlike normal keratinocytes, expressed alpha 5 beta 1 receptors. These observations suggest that cell-matrix interactions influence collagenase expression by epidermal cells. Indeed, as determined by ELISA, primary cultures of human keratinocytes grown on basement membrane proteins (Matrigel; Collaborative Research Inc., Bedford, MA) did not express significant levels of collagenase, whereas cells grown on type I collagen produced markedly increased levels. These results suggest that migrating keratinocytes actively involved in re-epithelialization acquire a collagenolytic phenotype upon contact with the dermal matrix. Images PMID:8254040

  8. Addressing Physical Inactivity among Developmentally Disabled Students through Visual Schedules and Social Stories

    ERIC Educational Resources Information Center

    Zimbelman, Merilee; Paschal, Angelia; Hawley, Suzanne R.; Molgaard, Craig A.; St. Romain, Theresa

    2007-01-01

    Introduction: This project tested visual schedules and social stories in a physical education setting in order to increase the physical activity of developmentally disabled students. Method: This cohort study design involved 17 physical education teachers in a training course with an initial survey and 7-month post-survey. The initial survey…

  9. Teaching Children with Autism to Play a Video Game Using Activity Schedules and Game-Embedded Simultaneous Video Modeling

    ERIC Educational Resources Information Center

    Blum-Dimaya, Alyssa; Reeve, Sharon A.; Reeve, Kenneth F.; Hoch, Hannah

    2010-01-01

    Children with autism have severe and pervasive impairments in social interactions and communication that impact most areas of daily living and often limit independent engagement in leisure activities. We taught four children with autism to engage in an age-appropriate leisure skill, playing the video game Guitar Hero II[TM], through the use of (a)…

  10. Schedule-Organizer Computer Program

    NASA Technical Reports Server (NTRS)

    Collazo, Fernando F.

    1990-01-01

    Schedule Organizer provides simple method for generating distribution lists. Contains readers' names for each task schedule defined by input files. Schedule Organizer (SO), Schedule Tracker (ST) (COSMIC program MSC-21526), and Schedule Report Generator (SRG) (COSMIC program MSC-21527) computer programs manipulating data-base files in ways advantageous in scheduling. Written in PL/1 and DEC Command Language (DCL).

  11. Implicit trustworthiness ratings of self-resembling faces activate brain centers involved in reward.

    PubMed

    Platek, Steven M; Krill, Austen L; Wilson, Benjamin

    2009-01-01

    On the basis of Hamilton's (Hamilton, W. D. (1964). The genetical evolution of social behavior I, II. Journal of Theoretical Biology, 7, 17-52) theory of inclusive fitness, self-facial resemblance is hypothesized as a mechanism for self-referent phenotypic matching by which humans can detect kin. To understand the mechanisms underlying pro-sociality toward self-resembling faces, we investigated the neural correlates of implicit trustworthiness ratings for self-resembling faces. Here we show that idiosyncratic trustworthiness ratings of self-resembling faces predict brain activation in the ventral inferior, middle and medial frontal gyri, substrates involved in reward processing. These findings demonstrate that neural reward centers are implicated in evaluating implicit pro-social behaviors toward self-resembling faces. These findings suggest that humans have evolved to use neurocomputational architecture dedicated to face processing and reward evaluation for the differentiation of kin, which drives implicit idiosyncratic affectively regulated social interactions. PMID:18761362

  12. Carbohydrate binding activity in human spermatozoa: localization, specificity, and involvement in sperm-egg fusion.

    PubMed

    Gabriele, A; D'Andrea, G; Cordeschi, G; Properzi, G; Giammatteo, M; De Stefano, C; Romano, R; Francavilla, F; Francavilla, S

    1998-06-01

    Sperm carbohydrate binding activity is involved in gamete recognition. We identified a human sperm protein extracted under reducing conditions, and with a molecular mass of 65 kDa on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and which binds D-mannose coupled to albumin (DMA) in presence of cations and a neutral pH. Epifluorescence microscopy showed that fluorescein-DMA binds to dead or permeabilized sperm heads. The DMA-binding activity of human sperm heads was highly specific for a polysaccharide structure containing charged sugar residues. After capacitation, or induction of the acrosome reaction using solubilized zonae pellucidae, fluorescein-DMA was bound respectively to 10.3% (+/- 3.5%) and to 37.6% (+/- 2.1%) of viable sperm heads. The sequential analysis of viable spermatozoa for fluorescein-DMA binding and for rhodamine-Pisum sativum agglutinin binding, showed that DMA-binding sites are present in viable acrosome-reacted spermatozoa. Three dimensional analysis of fluorescence and ultrastructural studies showed that DMA-binding sites are mostly restricted to the sub-acrosomal space of the equatorial segment. Incubation of spermatozoa and zona-free hamster eggs in the presence of DMA was associated with a dose-dependent significant reduction in the number of spermatozoa bound to the oolemma, compared with a control, and to a dose-dependent inhibition of oocyte penetration. This effect was highly specific for DMA, suggesting that DMA-binding sites in human spermatozoa are involved in sperm-egg fusion. PMID:9665337

  13. A novel carotenoid cleavage activity involved in the biosynthesis of Citrus fruit-specific apocarotenoid pigments

    PubMed Central

    Rodrigo, María J.; Alquézar, Berta; Al-Babili, Salim

    2013-01-01

    Citrus is the first tree crop in terms of fruit production. The colour of Citrus fruit is one of the main quality attributes, caused by the accumulation of carotenoids and their derivative C30 apocarotenoids, mainly β-citraurin (3-hydroxy-β-apo-8′-carotenal), which provide an attractive orange-reddish tint to the peel of oranges and mandarins. Though carotenoid biosynthesis and its regulation have been extensively studied in Citrus fruits, little is known about the formation of C30 apocarotenoids. The aim of this study was to the identify carotenoid cleavage enzyme(s) [CCD(s)] involved in the peel-specific C30 apocarotenoids. In silico data mining revealed a new family of five CCD4-type genes in Citrus. One gene of this family, CCD4b1, was expressed in reproductive and vegetative tissues of different Citrus species in a pattern correlating with the accumulation of C30 apocarotenoids. Moreover, developmental processes and treatments which alter Citrus fruit peel pigmentation led to changes of β-citraurin content and CCD4b1 transcript levels. These results point to the involvement of CCD4b1 in β-citraurin formation and indicate that the accumulation of this compound is determined by the availability of the presumed precursors zeaxanthin and β-cryptoxanthin. Functional analysis of CCD4b1 by in vitro assays unequivocally demonstrated the asymmetric cleavage activity at the 7′,8′ double bond in zeaxanthin and β-cryptoxanthin, confirming its role in C30 apocarotenoid biosynthesis. Thus, a novel plant carotenoid cleavage activity targeting the 7′,8′ double bond of cyclic C40 carotenoids has been identified. These results suggest that the presented enzyme is responsible for the biosynthesis of C30 apocarotenoids in Citrus which are key pigments in fruit coloration. PMID:24006419

  14. The scheduling techniques of ESP2

    NASA Technical Reports Server (NTRS)

    Jaap, John P.; Davis, Elizabeth K.

    1988-01-01

    The Mission Analysis Division of the Systems Analysis and Integration Laboratory at the Marshall Space Flight Center has developed a robust automatic scheduler which can produce detailed schedules for the multi-step activities required for payload operations on the Space Station. This scheduler, a part of the Expert Scheduling Program (ESP2), has five components: the bookkeeper, checker, loader, selector, and explainer. The bookkeeper maintains the usage profiles for nondepletable resources, consumables, equipment, crew, and the times of all the steps for the payload activities for several different schedules simultaneously. The checker searches the data maintained by the bookkeeper and finds times when the constraints of each step of an activity are satisfied. The loader is an expert system that uses the techniques of forward chaining, depth-first searching, and backtracking to manage the workings of the checker so that activities are placed in the schedule without violating constraints (such as crew, resources, and orbit opportunities). The checker searches the data maintained by the bookkeeper and finds times when the constraints of each step of an activity are satisfied. The loader is an expert system which uses the techniques of forward chaining, depth-first searching, and backtracking to manage the workings of the checker so that activities are placed in the schedule without violating the constraints. The selector has several methods of choosing the next activity for the loader to schedule. The explainer shows the user why an activity was or was not scheduled at a certain time; it offers a unique graphical explanation of how the expert system (the loader) works.

  15. Functional responses and molecular mechanisms involved in histone-mediated platelet activation.

    PubMed

    Carestia, A; Rivadeneyra, L; Romaniuk, M A; Fondevila, C; Negrotto, S; Schattner, M

    2013-11-01

    Histones are highly alkaline proteins found in cell nuclei and they can be released by either dying or inflammatory cells. The recent observations that histones are major components of neutrophil extracellular traps and promote platelet aggregation and platelet-dependent thrombin generation have shown that these proteins are potent prothrombotic molecules. Because the mechanism(s) of platelet activation by histones are not completely understood, we explored the ability of individual recombinant human histones H1, H2A, H2B, H3 and H4 to induce platelet activation as well as the possible molecular mechanisms involved. All histones were substrates for platelet adhesion and spreading and triggered fibrinogen binding, aggregation, von Willebrand factor release, P-selectin and phosphatidylserine (PS) exposure and the formation of platelet-leukocyte aggregates; however, H4 was the most potent. Histone-mediated fibrinogen binding, P-selectin and PS exposure and the formation of mixed aggregates were potentiated by thrombin. Histones induced the activation of ERK, Akt, p38 and NFκB. Accordingly, histone-induced platelet activation was significantly impaired by pretreatment of platelets with inhibitors of ERK (U 0126), PI3K/Akt (Ly 294002), p38 (SB 203580) and NFκB (BAY 11-7082 and Ro 106-9920). Preincubation of platelets with either aspirin or dexamethasone markedly decreased fibrinogen binding and the adhesion mediated by histones without affecting P-selectin exposure. Functional platelet responses induced by H3 and H4, but not H1, H2A and H2B, were partially mediated through interaction with Toll-like receptors -2 and -4. Our data identify histones as important triggers of haemostatic and proinflammatory platelet responses, and only haemostatic responses are partially inhibited by anti-inflammatory drugs. PMID:23965842

  16. Decreased activity of neutrophils in the presence of diferuloylmethane (curcumin) involves protein kinase C inhibition.

    PubMed

    Jancinová, Viera; Perecko, Tomás; Nosál, Radomír; Kostálová, Daniela; Bauerová, Katarína; Drábiková, Katarína

    2009-06-10

    Diferuloylmethane (curcumin) has been shown to act beneficially in arthritis, particularly through downregulated expression of proinflammatory cytokines and collagenase as well as through the modulated activities of T lymphocytes and macrophages. In this study its impact on activated neutrophils was investigated both in vitro and in experimental arthritis. Formation of reactive oxygen species in neutrophils was recorded on the basis of luminol- or isoluminol-enhanced chemiluminescence. Phosphorylation of neutrophil protein kinases C alpha and beta II was assessed by Western blotting, using phosphospecific antibodies. Adjuvant arthritis was induced in Lewis rats by heat-killed Mycobacterium butyricum. Diferuloylmethane or methotrexate was administered over a period of 28 days after arthritis induction. Under in vitro conditions, diferuloylmethane (1-100 microM) reduced dose-dependently oxidant formation both at extra- and intracellular level and it effectively reduced protein kinase C activation. Adjuvant arthritis was accompanied by an increased number of neutrophils in blood and by a more pronounced spontaneous as well as PMA (phorbol myristate acetate) stimulated chemiluminescence. Whereas the arthritis-related alterations in neutrophil count and in spontaneous chemiluminescence were not modified by diferuloylmethane, the increased reactivity of neutrophils to PMA was less evident in diferuloylmethane-treated animals. The effects of diferuloylmethane were comparable with those of methotrexate. Diferuloylmethane was found to be a potent inhibitor of neutrophil functions both in vitro and in experimental arthritis. As neutrophils are considered to be cells with the greatest capacity to inflict damage within diseased joints, the observed effects could represent a further mechanism involved in the antirheumatic activity of diferuloylmethane. PMID:19371737

  17. Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma.

    PubMed

    Syed, Deeba N; Lall, Rahul K; Chamcheu, Jean Christopher; Haidar, Omar; Mukhtar, Hasan

    2014-12-01

    The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytotoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up-regulation of ER stress markers including IRE1α, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMP-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity. PMID:25016296

  18. Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma

    PubMed Central

    Chamcheu, Jean Christopher; Haidar, Omar; Mukhtar, Hasan

    2014-01-01

    The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up- regulation of ER stress markers including IRE1α, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16 days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMPK-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity. PMID:25016296

  19. Aldrin-induced locomotor activity: possible involvement of the central GABAergic-cholinergic-dopaminergic interaction.

    PubMed

    Jamaluddin, S; Poddar, M K

    2001-01-01

    Aldrin (5 mg/kg/day, p.o.) under nontolerant condition, administered either for a single day or for 12 consecutive days, enhanced locomotor activity (LA) of rats. The increase in LA was greater in rats treated with aldrin for 12 consecutive days than that observed with a single dose. The aim of the present study is to evaluate the involvement of possible interactions of central GABAergic, cholinergic and dopaminergic systems using their agonist(s) and antagonist(s) in the regulation of LA in aldrin nontolerant rats. Administration of either L-DOPA along with carbidopa or bicuculline potentiated aldrin-induced increase in LA under nontolerant condition as well as LA of the control rats. Treatment with muscimol, haloperidol, atropine or physostigmine all decreased the LA of both aldrin nontolerant and control rats. Further, the application of (a) haloperidol along with bicuculline, atropine or physostigmine and (b) physostigmine along with bicuculline or L-DOPA + carbidopa significantly reduced LA but L-DOPA + carbidopa along with atropine or bicuculline increased LA of the control rats. These agonist(s)/antagonist(s)-induced decrease or increase in LA of the control rats were attenuated or potentiated, respectively, when those agonist(s)/antagonist(s) under abovementioned condition were administered to aldrin nontolerant rats. The attenuating or potentiating effects of aldrin on agonist(s)/antagonist(s) (either individually or in different combinations)-induced change in LA were greater in rats treated with aldrin for 12 consecutive days than that observed with a single-dose aldrin treatment. These results suggest that aldrin, under nontolerant condition, reduces central GABAergic activity and increases LA by activating dopaminergic system via inhibition of cholinergic activity. The treatment with aldrin for 12 consecutive days produces greater effect than that caused by a single-day treatment. PMID:11785907

  20. Integrated resource scheduling in a distributed scheduling environment

    NASA Technical Reports Server (NTRS)

    Zoch, David; Hall, Gardiner

    1988-01-01

    The Space Station era presents a highly-complex multi-mission planning and scheduling environment exercised over a highly distributed system. In order to automate the scheduling process, customers require a mechanism for communicating their scheduling requirements to NASA. A request language that a remotely-located customer can use to specify his scheduling requirements to a NASA scheduler, thus automating the customer-scheduler interface, is described. This notation, Flexible Envelope-Request Notation (FERN), allows the user to completely specify his scheduling requirements such as resource usage, temporal constraints, and scheduling preferences and options. The FERN also contains mechanisms for representing schedule and resource availability information, which are used in the inter-scheduler inconsistency resolution process. Additionally, a scheduler is described that can accept these requests, process them, generate schedules, and return schedule and resource availability information to the requester. The Request-Oriented Scheduling Engine (ROSE) was designed to function either as an independent scheduler or as a scheduling element in a network of schedulers. When used in a network of schedulers, each ROSE communicates schedule and resource usage information to other schedulers via the FERN notation, enabling inconsistencies to be resolved between schedulers. Individual ROSE schedules are created by viewing the problem as a constraint satisfaction problem with a heuristically guided search strategy.

  1. Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1.

    PubMed

    Ogura, Masahito; Nakamura, Yasuhiko; Tanaka, Daisuke; Zhuang, Xiaotong; Fujita, Yoshihito; Obara, Akio; Hamasaki, Akihiro; Hosokawa, Masaya; Inagaki, Nobuya

    2010-02-26

    SIR2 protein, an NAD-dependent deacetylase, is localized to nucleus and is involved in life span extension by calorie restriction in yeast. In mammals, among the seven SIR2 homologues (SIRT1-7), SIRT3, 4, and 5 are localized to mitochondria. As SIRT5 mRNA levels in liver are increased by fasting, the physiological role of SIRT5 was investigated in liver of SIRT5-overexpressing transgenic (SIRT5 Tg) mice. We identified carbamoyl phosphate synthetase 1 (CPS1), a key enzyme of the urea cycle that catalyzes condensation of ammonia with bicarbonate to form carbamoyl phosphate, as a target of SIRT5 by two-dimensional electrophoresis comparing mitochondrial proteins in livers of SIRT5 Tg and wild-type mice. CPS1 protein was more deacetylated and activated in liver of SIRT5 Tg mice than in wild-type. In addition, urea production was upregulated in hepatocytes of SIRT5 Tg mice. These results agree with those of a previous study using SIRT5 knockout (KO) mice. Because ammonia generated during fasting is toxic, SIRT5 protein might play a protective role by converting ammonia to non-toxic urea through deacetylation and activation of CPS1. PMID:20097174

  2. Involvement of JNK and Caspase Activation in Hoiamide A-Induced Neurotoxicity in Neocortical Neurons

    PubMed Central

    Cao, Zhengyu; Li, Xichun; Zou, Xiaohan; Greenwood, Michael; Gerwick, William H.; Murray, Thomas F.

    2015-01-01

    The frequent occurrence of Moorea producens (formerly Lyngbya majuscula) blooms has been associated with adverse effects on human health. Hoiamide A is a structurally unique cyclic depsipeptide isolated from an assemblage of the marine cyanobacteria M. producens and Phormidium gracile. We examined the influence of hoiamide A on neurite outgrowth in neocortical neurons and found that it suppressed neurite outgrowth with an IC50 value of 4.89 nM. Further study demonstrated that hoiamide A stimulated lactic acid dehydrogenase (LDH) efflux, nuclear condensation and caspase-3 activity with EC50 values of 3.66, 2.55 and 4.33 nM, respectively. These data indicated that hoiamide A triggered a unique neuronal death profile that involves both necrotic and apoptotic mechanisms. The similar potencies and similar time-response relationships between LDH efflux and caspase-3 activation/nuclear condensation suggested that both necrosis and apoptosis may derive from interaction with a common molecular target. The broad-spectrum caspase inhibitor, Z-VAD-FMK completely inhibited hoiamide A-induced neurotoxicity. Additionally, hoiamide A stimulated JNK phosphorylation, and a JNK inhibitor attenuated hoiamide A-induced neurotoxicity. Collectively, these data demonstrate that hoiamide A-induced neuronal death requires both JNK and caspase signaling pathways. The potent neurotoxicity and unique neuronal cell death profile of hoiamide A represents a novel neurotoxic chemotype from marine cyanobacteria. PMID:25675001

  3. Involvement of both PKS and NRPS in antibacterial activity in Lysobacter enzymogenes OH11

    PubMed Central

    Zhang, Juan; Du, Liangcheng; Liu, Fengquan; Xu, Feifei; Hu, Baishi; Venturi, Vittorio; Qian, Guoliang

    2014-01-01

    Polyketides and nonribosomal peptides represent two large families of natural products (NPs) with diverse structures and important functions. They are synthesized by polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS), respectively. Lysobacter enzymogenes is emerging as a novel biocontrol agent against pathogens of crop plants and a new source of bioactive NPs, such as antibacterial antibiotic WAP-8294A2 and antifungal antibiotic HSAF. Genome survey of strain OH11, a Chinese L. enzymogenes isolate, detected four novel PKS, NRPS or hybrid gene clusters, designed as cluster A to D. We further individually mutated five genes (PKS or NRPS) located in these four gene clusters, and showed that a PKS gene in cluster A and an NRPS gene in cluster D were involved in the antibacterial activity via a WAP-8294A2 dependent way. The data also showed that none of the five genes was associated with antifungal activity and the regulation of HSAF biosynthesis. Our results reveal the unusual regulatory role of these PKS and NRPS genes that were discovered from genome mining in L. enzymogenes. PMID:24801439

  4. Mechanisms involved in Escherichia coli and Serratia marcescens removal during activated sludge wastewater treatment

    PubMed Central

    Orruño, Maite; Garaizabal, Idoia; Bravo, Zaloa; Parada, Claudia; Barcina, Isabel; Arana, Inés

    2014-01-01

    Wastewater treatment reduces environmental contamination by removing gross solids and mitigating the effects of pollution. Treatment also reduces the number of indicator organisms and pathogens. In this work, the fates of two coliform bacteria, Escherichia coli and Serratia marcescens, were analyzed in an activated sludge process to determine the main mechanisms involved in the reduction of pathogenic microorganisms during wastewater treatment. These bacteria, modified to express green fluorescent protein, were inoculated in an activated sludge unit and in batch systems containing wastewater. The results suggested that, among the different biological factors implied in bacterial removal, bacterivorous protozoa play a key role. Moreover, a representative number of bacteria persisted in the system as free-living or embedded cells, but their distribution into liquid or solid fractions varied depending on the bacterium tested, questioning the real value of bacterial indicators for the control of wastewater treatment process. Additionally, viable but nonculturable cells constituted an important part of the bacterial population adhered to solid fractions, what can be derived from the competition relationships with native bacteria, present in high densities in this environment. These facts, taken together, emphasize the need for reliable quantitative and qualitative analysis tools for the evaluation of pathogenic microbial composition in sludge, which could represent an undefined risk to public health and ecosystem functions when considering its recycling. PMID:25044599

  5. HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation

    PubMed Central

    Lin, Shenglan; Wang, Yana; Zhang, Xiaojin; Kong, Qiuyue; Li, Chuanfu; Li, Yuehua; Ding, Zhengnian

    2016-01-01

    Aging-induced cardiac dysfunction is a prominent feature of cardiac aging. Heat shock protein 27 (HSP27) protects cardiac function against ischemia or chemical challenge. We hypothesized that HSP27 attenuates cardiac aging. Transgenic (Tg) mice with cardiac-specific expression of the HSP27 gene and wild-type (WT) littermates were employed in the experiments. Echocardiography revealed a significant decline in the cardiac function of old WT mice compared with young WT mice. In striking contrast, the aging-induced impairment of cardiac function was attenuated in old Tg mice compared with old WT mice. Levels of cardiac aging markers were lower in old Tg mouse hearts than in old WT mouse hearts. Less interstitial fibrosis and lower contents of reactive oxygen species and ubiquitin-conjugated proteins were detected in old Tg hearts than in old WT hearts. Furthermore, old Tg hearts demonstrated lower accumulation of LC3-II and p62 than old WT hearts. Levels of Atg13, Vps34, and Rab7 were also higher in old Tg hearts than in old WT hearts. Additionally, old Tg hearts had higher levels of PINK1 and Parkin than old WT hearts, suggesting that mitophagy was activated in old Tg hearts. Taken together, HSP27 alleviated cardiac aging and this action involved antioxidation and mitophagy activation. PMID:27110324

  6. Mechanisms involved in Escherichia coli and Serratia marcescens removal during activated sludge wastewater treatment.

    PubMed

    Orruño, Maite; Garaizabal, Idoia; Bravo, Zaloa; Parada, Claudia; Barcina, Isabel; Arana, Inés

    2014-10-01

    Wastewater treatment reduces environmental contamination by removing gross solids and mitigating the effects of pollution. Treatment also reduces the number of indicator organisms and pathogens. In this work, the fates of two coliform bacteria, Escherichia coli and Serratia marcescens, were analyzed in an activated sludge process to determine the main mechanisms involved in the reduction of pathogenic microorganisms during wastewater treatment. These bacteria, modified to express green fluorescent protein, were inoculated in an activated sludge unit and in batch systems containing wastewater. The results suggested that, among the different biological factors implied in bacterial removal, bacterivorous protozoa play a key role. Moreover, a representative number of bacteria persisted in the system as free-living or embedded cells, but their distribution into liquid or solid fractions varied depending on the bacterium tested, questioning the real value of bacterial indicators for the control of wastewater treatment process. Additionally, viable but nonculturable cells constituted an important part of the bacterial population adhered to solid fractions, what can be derived from the competition relationships with native bacteria, present in high densities in this environment. These facts, taken together, emphasize the need for reliable quantitative and qualitative analysis tools for the evaluation of pathogenic microbial composition in sludge, which could represent an undefined risk to public health and ecosystem functions when considering its recycling. PMID:25044599

  7. Neuroinformatics analyses reveal GABAt and SSADH as major proteins involved in anticonvulsant activity of valproic acid.

    PubMed

    Piplani, Sakshi; Verma, Prabhakar Kumar; Kumar, Ajit

    2016-07-01

    The unequivocal hypotheses about anticonvulsant activity of valproic acid (VPA) have always been a basic hurdle in designing next generation neurotherapeutics, particularly the anti-epileptic drugs. The present study reports about a comprehensive in-silico investigation into qualitative and quantitative binding of VPA and corresponding natural ligands of four major enzymes involved in neurotransmissions, namely-GABA transaminase (GABAt), α-keto glutarate dehydrogenase (α-KGDH), Succinate Semialdehyde dehydrogenase (SSADH) and Glutamate Decarboxylase (GAD), respectively. The molecular docking analyses revealed that VPA inhibits GABAt and α-KGDH through allosteric while SSADH through competitive mode of binding. There is an observed elevation in binding of glutamate over GAD in the presence of VPA. The docking inhibition constant (Ki) of VPA to all the studied enzymatic receptors were observed to be well below the therapeutic concentration of VPA in blood, except for α-KGDH, thus favouring GABAergic over glutamatergic mode of anticonvulsant activity of VPA. The report is probably the first comprehensive in-silico molecular study about VPA action. PMID:27261619

  8. Automated telescope scheduling

    NASA Technical Reports Server (NTRS)

    Johnston, Mark D.

    1988-01-01

    With the ever increasing level of automation of astronomical telescopes the benefits and feasibility of automated planning and scheduling are becoming more apparent. Improved efficiency and increased overall telescope utilization are the most obvious goals. Automated scheduling at some level has been done for several satellite observatories, but the requirements on these systems were much less stringent than on modern ground or satellite observatories. The scheduling problem is particularly acute for Hubble Space Telescope: virtually all observations must be planned in excruciating detail weeks to months in advance. Space Telescope Science Institute has recently made significant progress on the scheduling problem by exploiting state-of-the-art artificial intelligence software technology. What is especially interesting is that this effort has already yielded software that is well suited to scheduling groundbased telescopes, including the problem of optimizing the coordinated scheduling of more than one telescope.

  9. Automated telescope scheduling

    NASA Astrophysics Data System (ADS)

    Johnston, Mark D.

    1988-08-01

    With the ever increasing level of automation of astronomical telescopes the benefits and feasibility of automated planning and scheduling are becoming more apparent. Improved efficiency and increased overall telescope utilization are the most obvious goals. Automated scheduling at some level has been done for several satellite observatories, but the requirements on these systems were much less stringent than on modern ground or satellite observatories. The scheduling problem is particularly acute for Hubble Space Telescope: virtually all observations must be planned in excruciating detail weeks to months in advance. Space Telescope Science Institute has recently made significant progress on the scheduling problem by exploiting state-of-the-art artificial intelligence software technology. What is especially interesting is that this effort has already yielded software that is well suited to scheduling groundbased telescopes, including the problem of optimizing the coordinated scheduling of more than one telescope.

  10. Achieving reutilization of scheduling software through abstraction and generalization

    NASA Technical Reports Server (NTRS)

    Wilkinson, George J.; Monteleone, Richard A.; Weinstein, Stuart M.; Mohler, Michael G.; Zoch, David R.; Tong, G. Michael

    1995-01-01

    Reutilization of software is a difficult goal to achieve particularly in complex environments that require advanced software systems. The Request-Oriented Scheduling Engine (ROSE) was developed to create a reusable scheduling system for the diverse scheduling needs of the National Aeronautics and Space Administration (NASA). ROSE is a data-driven scheduler that accepts inputs such as user activities, available resources, timing contraints, and user-defined events, and then produces a conflict-free schedule. To support reutilization, ROSE is designed to be flexible, extensible, and portable. With these design features, applying ROSE to a new scheduling application does not require changing the core scheduling engine, even if the new application requires significantly larger or smaller data sets, customized scheduling algorithms, or software portability. This paper includes a ROSE scheduling system description emphasizing its general-purpose features, reutilization techniques, and tasks for which ROSE reuse provided a low-risk solution with significant cost savings and reduced software development time.

  11. Involvement of IL-1 in the Maintenance of Masseter Muscle Activity and Glucose Homeostasis

    PubMed Central

    Chiba, Ko; Tsuchiya, Masahiro; Koide, Masashi; Hagiwara, Yoshihiro; Sasaki, Keiichi; Hattori, Yoshinori; Watanabe, Makoto; Sugawara, Shunji; Kanzaki, Makoto; Endo, Yasuo

    2015-01-01

    Physical exercise reportedly stimulates IL-1 production within working skeletal muscles, but its physiological significance remains unknown due to the existence of two distinct IL-1 isoforms, IL-1α and IL-1β. The regulatory complexities of these two isoforms, in terms of which cells in muscles produce them and their distinct/redundant biological actions, have yet to be elucidated. Taking advantage of our masticatory behavior (Restrained/Gnawing) model, we herein show that IL-1α/1β-double-knockout (IL-1-KO) mice exhibit compromised masseter muscle (MM) activity which is at least partially attributable to abnormalities of glucose handling (rapid glycogen depletion along with impaired glucose uptake) and dysfunction of IL-6 upregulation in working MMs. In wild-type mice, masticatory behavior clearly increased IL-1β mRNA expression but no incremental protein abundance was detectable in whole MM homogenates, whereas immunohistochemical staining analysis revealed that both IL-1α- and IL-1β-immunopositive cells were recruited around blood vessels in the perimysium of MMs after masticatory behavior. In addition to the aforementioned phenotype of IL-1-KO mice, we found the IL-6 mRNA and protein levels in MMs after masticatory behavior to be significantly lower in IL-1-KO than in WT. Thus, our findings confirm that the locally-increased IL-1 elicited by masticatory behavior, although present small in amounts, contributes to supporting MM activity by maintaining normal glucose homeostasis in these muscles. Our data also underscore the importance of IL-1-mediated local interplay between autocrine myokines including IL-6 and paracrine cytokines in active skeletal muscles. This interplay is directly involved in MM performance and fatigability, perhaps mediated through maintaining muscular glucose homeostasis. PMID:26599867

  12. Pathogenesis of aortic dilatation in mucopolysaccharidosis VII mice may involve complement activation

    PubMed Central

    Baldo, Guilherme; Wu, Susan; Howe, Ruth A.; Ramamoothy, Meera; Knutsen, Russell H.; Fang, Jiali; Mecham, Robert P.; Liu, Yuli; Wu, Xiaobo; Atkinson, John P.; Ponder, Katherine P.

    2012-01-01

    Mucopolysaccharidosis VII (MPS VII) is due to mutations within the gene encoding the lysosomal enzyme β-glucuronidase, and results in the accumulation of glycosaminoglycans. MPS VII causes aortic dilatation and elastin fragmentation, which is associated with upregulation of the elastases cathepsin S (CtsS) and matrix metalloproteinase 12 (MMP12). To test the role of these enzymes, MPS VII mice were crossed with mice deficient in CtsS or MMP12, and the effect upon aortic dilatation was determined. CtsS deficiency did not protect against aortic dilatation in MPS VII mice, but also failed to prevent an upregulation of cathepsin enzyme activity. Further analysis with substrates and inhibitors specific for particular cathepsins suggests that this enzyme activity was due to CtsB, which could contribute to elastin fragmentation. Similarly, MMP12 deficiency and deficiency of both MMP12 and CtsS could not prevent aortic dilatation in MPS VII mice. Microarray and reverse-transcriptase real-time PCR were performed to look for upregulation of other elastases. This demonstrated that mRNA for complement component D was elevated in MPS VII mice, while immunostaining demonstrated high levels of complement component C3 on surfaces within the aortic media. Finally, we demonstrate that neonatal intravenous injection of a retroviral vector encoding β-glucuronidase reduced aortic dilatation. We conclude that neither CtsS nor MMP12 are necessary for elastin fragmentation in MPS VII mouse aorta, and propose that CtsB and/or complement component D may be involved. Complement may be activated by the GAGs that accumulate, and may play a role in signal transduction pathways that upregulate elastases. PMID:21944884

  13. Nelfinavir and other protease inhibitors in cancer: mechanisms involved in anticancer activity

    PubMed Central

    Koltai, Tomas

    2015-01-01

    Objective: To review the mechanisms of anti-cancer activity of nelfinavir and other protease inhibitors (PIs) based on evidences reported in the published literature. Methods: We extensively reviewed the literature concerning nelfinavir (NFV) as an off target anti-cancer drug and other PIs. A classification of PIs based on anti-cancer mode of action was proposed. Controversies regarding nelfinavir mode of action were also addressed. Conclusions: The two main mechanisms involved in anti-cancer activity are endoplasmic reticulum stress-unfolded protein response pathway and Akt inhibition. However there are many other effects, partially dependent and independent of those mentioned, that may be useful in cancer treatment, including MMP-9 and MMP-2 inhibition, down-regulation of CDK-2, VEGF, bFGF, NF-kB, STAT-3, HIF-1 alfa, IGF, EGFR, survivin, BCRP, androgen receptor, proteasome, fatty acid synthase (FAS), decrease in cellular ATP concentration and upregulation of TRAIL receptor DR5, Bax, increased radiosensitivity, and autophagy. The end result of all these effects is slower growth, decreased angiogenesis, decreased invasion and increased apoptosis, which means reduced proliferation and increased cancer cells death. PIs may be classified according to their anticancer activity at clinically achievable doses, in AKT inhibitors, ER stressors and Akt inhibitors/ER stressors. Beyond the phase I trials that have been recently completed, adequately powered and well-designed clinical trials are needed in the various cancer type settings, and specific trials where NFV is tested in association with other known anti-cancer pharmaceuticals should be sought, in order to find an appropriate place for NFV in cancer treatment. The analysis of controversies on the molecular mechanisms of NFV hints to the possibility that NFV works in a different way in tumor cells and in hepatocytes and adipocytes. PMID:26097685

  14. Involvement of the histamine H1 receptor in the regulation of sympathetic nerve activity.

    PubMed

    Murakami, Manabu; Yoshikawa, Takeo; Nakamura, Tadaho; Ohba, Takayoshi; Matsuzaki, Yasushi; Sawamura, Daisuke; Kuwasako, Kenji; Yanagisawa, Teruyuki; Ono, Kyouichi; Nakaji, Shigeyuki; Yanai, Kazuhiko

    2015-03-13

    The histamine system is involved in the regulation of the autonomic nervous system. We used gene-targeted mice to investigate the role of histamine receptors in the regulation of the sympathetic nervous system. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed histamine H1, H2, and H3 receptor expression in the superior cervical ganglion, which contains sympathetic nerve cell bodies. We measured the heart rate variability (HRV), the changes in the beat-to-beat heart rate, which is widely used to assess autonomic activity in the heart. H1 blockade attenuated the baroreflex-mediated changes in heart rate in wild-type (WT) mice, whereas the heart rate response to H2- and H3-specific blockers was unaffected. l-Histidine decarboxylase (HDC) expression in the superior cervical ganglion of H1R-null mice was higher than that in WT controls, whereas the enzyme levels in H2R- and H3R-null mice were not significantly different from those in the WT. All mutant mice (H1R-, H2R-, and H3R-null mice) showed normal electrocardiogram (ECG) patterns with little modification in ECG parameters and the expected response to the β-adrenergic blocker propranolol. Similar to our findings in WT mice, H1 blockade attenuated the baroreflex-mediated heart rate change in H1R-null mice, whereas the heart rate response was unaffected in H2R- and H3R-null mice. The HRV analysis revealed relatively unstable RR intervals, an increased standard deviation of the interbeat interval (SDNN), and low-frequency (LF) component in H1R-null mice compared with the other groups, suggesting that sympathetic nerve activity was altered in H1R-null mice. Taken together, our findings indicate that H1 receptors play a major role in the regulation of sympathetic nerve activity. PMID:25680462

  15. Mothers' and Fathers' Involvement in Home Activities with Their Children: Psychosocial Factors and the Role of Parental Self-Efficacy

    ERIC Educational Resources Information Center

    Giallo, Rebecca; Treyvaud, Karli; Cooklin, Amanda; Wade, Catherine

    2013-01-01

    Parent involvement in play, learning, and everyday home activities is important for promoting children's cognitive and language development. The aims of the study were to (a) examine differences between mothers' and fathers' self-reported involvement with their children, (b) explore the relationship between child, parent and family factors, and…

  16. Parent Involvement Activities in School Improvement Plans in the Northwest Region. Summary. Issues & Answers. REL 2008-No. 064

    ERIC Educational Resources Information Center

    Speth, Timothy; Saifer, Steffen; Forehand, Gregory

    2008-01-01

    This document presents a summary of the larger report, "Parent Involvement Activities in School Improvement Plans in the Northwest Region." Although the No Child Left Behind Act of 2001 (NCLB) spells out parent involvement requirements for schools in need of improvement, the majority of the Northwest Region school improvement plans reviewed failed…

  17. ED-12WIDESPREAD SYSTEMIC METASTASES FROM MEDULLOBLASTOMA WITHOUT EVIDENCE OF ACTIVE CNS INVOLVEMENT: A CASE SERIES

    PubMed Central

    Kumthekar, Priya; Singh, Simran; Smiley, Natasha Pillay; Lulla, Rishi

    2014-01-01

    without active CNS involvement. Follow up imaging for medulloblastoma patients should potentially include systemic surveillance in addition to routine neuroimaging.

  18. Application of two-phase flow modeling as a basis for scheduling corrosion maintenance activities in wet sour gas pipelines

    SciTech Connect

    Richardson, D.; Bich, N.N.

    1997-08-01

    Pipeline failures attributed to internal corrosion in the oil and gas producing industry have not been decreasing despite the many corrosion mitigation, monitoring and inspection programs implemented. This paper describes how preliminary investigations for evaluating the susceptibility of internal corrosion for wet sour gas pipelines have been based on integrating the latest knowledge in fluid flow and sour gas corrosion mechanisms. It is anticipated future efforts to correlate the onset of slug flow regime with historical corrosion and inspection data may lead to development of an improved criteria for predicting the onset of corrosive water traps and for triggering appropriate maintenance activities. This paper provides details of two corrosion failure Case Studies where application of flow modeling has improved the understanding of the operating hazards that contributed to the formation of a corrosive environment leading to high-rate initiation and growth of localized pitting corrosion. Preliminary analysis indicates slug flow pattern, and long water residence time of water within stagnant traps increases the likelihood of pitting corrosion.

  19. Fatty acid transport and activation and the expression patterns of genes involved in fatty acid trafficking.

    PubMed

    Sandoval, Angel; Fraisl, Peter; Arias-Barrau, Elsa; Dirusso, Concetta C; Singer, Diane; Sealls, Whitney; Black, Paul N

    2008-09-15

    These studies defined the expression patterns of genes involved in fatty acid transport, activation and trafficking using quantitative PCR (qPCR) and established the kinetic constants of fatty acid transport in an effort to define whether vectorial acylation represents a common mechanism in different cell types (3T3-L1 fibroblasts and adipocytes, Caco-2 and HepG2 cells and three endothelial cell lines (b-END3, HAEC, and HMEC)). As expected, fatty acid transport protein (FATP)1 and long-chain acyl CoA synthetase (Acsl)1 were the predominant isoforms expressed in adipocytes consistent with their roles in the transport and activation of exogenous fatty acids destined for storage in the form of triglycerides. In cells involved in fatty acid processing including Caco-2 (intestinal-like) and HepG2 (liver-like), FATP2 was the predominant isoform. The patterns of Acsl expression were distinct between these two cell types with Acsl3 and Acsl5 being predominant in Caco-2 cells and Acsl4 in HepG2 cells. In the endothelial lines, FATP1 and FATP4 were the most highly expressed isoforms; the expression patterns for the different Acsl isoforms were highly variable between the different endothelial cell lines. The transport of the fluorescent long-chain fatty acid C(1)-BODIPY-C(12) in 3T3-L1 fibroblasts and 3T3-L1 adipocytes followed typical Michaelis-Menten kinetics; the apparent efficiency (k(cat)/K(T)) of this process increases over 2-fold (2.1 x 10(6)-4.5 x 10(6)s(-1)M(-1)) upon adipocyte differentiation. The V(max) values for fatty acid transport in Caco-2 and HepG2 cells were essentially the same, yet the efficiency was 55% higher in Caco-2 cells (2.3 x 10(6)s(-1)M(-1) versus 1.5 x 10(6)s(-1)M(-1)). The kinetic parameters for fatty acid transport in three endothelial cell types demonstrated they were the least efficient cell types for this process giving V(max) values that were nearly 4-fold lower than those defined form 3T3-L1 adipocytes, Caco-2 cells and HepG2 cells. The

  20. The Effects of Adolescent Activities on Delinquency: A Differential Involvement Approach

    ERIC Educational Resources Information Center

    Wong, Siu Kwong

    2005-01-01

    T. Hirschi's (1969, "Causes of Delinquency." University of California Press, Berkeley, CA) control theory proposes that involvement, as an element of the social bond, should reduce delinquency. But, research studies have found that the effect of involvement is rather weak. This study reformulates Hirschi's involvement hypothesis by posing…

  1. Transportation Baseline Schedule

    SciTech Connect

    Fawcett, Ricky Lee; John, Mark Earl

    2000-01-01

    The “1999 National Transportation Program - Transportation Baseline Report” presents data that form a baseline to enable analysis and planning for future Department of Energy (DOE) Environmental Management (EM) waste/material transportation. The companion “1999 Transportation ‘Barriers’ Analysis” analyzes the data and identifies existing and potential problems that may prevent or delay transportation activities based on the data presented. The “1999 Transportation Baseline Schedule” (this report) uses the same data to provide an overview of the transportation activities of DOE EM waste/materials. This report can be used to identify areas where stakeholder interface is needed, and to communicate to stakeholders the quantity/schedule of shipments going through their area. Potential bottlenecks in the transportation system can be identified; the number of packages needed, and the capacity needed at receiving facilities can be planned. This report offers a visualization of baseline DOE EM transportation activities for the 11 major sites and the “Geologic Repository Disposal” site (GRD).

  2. PRESS40: a project for involving students in active seismic risk mitigation

    NASA Astrophysics Data System (ADS)

    Barnaba, Carla; Contessi, Elisa; Rosa Girardi, Maria

    2016-04-01

    To memorialize the anniversary of the 1976 Friuli earthquake, the Istituto Statale di Istruzione Superiore "Magrini Marchetti" in Gemona del Friuli (NE Italy), with the collaboration of the Istituto Nazionale di Oceanografia e di Geofisica Sperimentale (OGS), has promoted the PRESS40 Project (Prevenzione Sismica nella Scuola a 40 anni dal terremoto del Friuli, that in English sounds like "Seismic Prevention at School 40 years later the Friuli earthquake"). The project has developed in the 2015-2016 school year, starting from the 40th anniversary of the Friuli earthquake, and it aims to disseminate historical memory, seismic culture and awareness of seismic safety in the young generations, too often unconscious of past experiences, as recent seismic hazard perception tests have demonstrated. The basic idea of the PRESS40 Project is to involve the students in experimental activities to be active part of the seismic mitigation process. The Project is divided into two main parts, the first one in which students learn-receive knowledge from researchers, and the second one in which they teach-bring knowledge to younger students. In the first part of the project, 75 students of the "Magrini Marchetti" school acquired new geophysical data, covering the 23 municipalities from which they come from. These municipalities represent a wide area affected by the 1976 Friuli earthquake. In each locality a significant site was examined, represented by a school area. At least, 127 measurements of ambient noise have been acquired. Data processing and interpretation of all the results are still going on, under the supervision of OGS researchers.The second part of the project is planned for the early spring, when the students will present the results of geophysical survey to the younger ones of the monitored schools and to the citizens in occasion of events to commemorate the 40th anniversary of the Friuli earthquake.

  3. Utilization of iron-catecholamine complexes involving ferric reductase activity in Listeria monocytogenes.

    PubMed Central

    Coulanges, V; Andre, P; Ziegler, O; Buchheit, L; Vidon, D J

    1997-01-01

    Listeria monocytogenes is a ubiquitous potentially pathogenic organism requiring iron for growth and virulence. Although it does not produce siderophores, L. monocytogenes is able to obtain iron by using either exogenous siderophores produced by various microorganisms or natural catechol compounds widespread in the environment. In the presence of tropolone, an iron-chelating agent, growth of L. monocytogenes is completely inhibited. However, the growth inhibition can be relieved by the addition of dopamine or norepinephrine under their different isomeric forms, while the catecholamine derivatives 4-hydroxy-3-methoxyphenylglycol and normetanephrine did not relieve the inhibitory effect of tropolone. Preincubation of L. monocytogenes with chlorpromazine and yohimbine did not antagonize the growth-promoting effect of catecholamines in iron-complexed medium. In addition, norepinephrine stimulated the growth-promoting effect induced by human transferrin in iron-limited medium. Furthermore, dopamine and norepinephrine allowed 55Fe uptake by iron-deprived bacterial cells. The uptake of iron was energy dependent, as indicated by inhibition of 55Fe uptake at 0 degrees C as well as by preincubating the bacteria with KCN. Inhibition of 55Fe uptake by L. monocytogenes was also observed in the presence of Pt(II). Moreover, when assessed by a whole-cell ferric reductase assay, reductase activity of L. monocytogenes was inhibited by Pt(II). These data demonstrate that dopamine and norepinephrine can function as siderophore-like compounds in L. monocytogenes owing to their ortho-diphenol function and that catecholamine-mediated iron acquisition does not involve specific catecholamine receptors but acts through a cell-bound ferrireductase activity. PMID:9199450

  4. Lack of Involvement of CEP Adducts in TLR Activation and in Angiogenesis

    PubMed Central

    Gounarides, John; Cobb, Jennifer S.; Zhou, Jing; Cook, Frank; Yang, Xuemei; Yin, Hong; Meredith, Erik; Rao, Chang; Huang, Qian; Xu, YongYao; Anderson, Karen; De Erkenez, Andrea; Liao, Sha-Mei; Crowley, Maura; Buchanan, Natasha; Poor, Stephen; Qiu, Yubin; Fassbender, Elizabeth; Shen, Siyuan; Woolfenden, Amber; Jensen, Amy; Cepeda, Rosemarie; Etemad-Gilbertson, Bijan; Giza, Shelby; Mogi, Muneto; Jaffee, Bruce; Azarian, Sassan

    2014-01-01

    Proteins that are post-translationally adducted with 2-(ω-carboxyethyl)pyrrole (CEP) have been proposed to play a pathogenic role in age-related macular degeneration, by inducing angiogenesis in a Toll Like Receptor 2 (TLR2)-dependent manner. We have investigated the involvement of CEP adducts in angiogenesis and TLR activation, to assess the therapeutic potential of inhibiting CEP adducts and TLR2 for ocular angiogenesis. As tool reagents, several CEP-adducted proteins and peptides were synthetically generated by published methodology and adduction was confirmed by NMR and LC-MS/MS analyses. Structural studies showed significant changes in secondary structure in CEP-adducted proteins but not the untreated proteins. Similar structural changes were also observed in the treated unadducted proteins, which were treated by the same adduction method except for one critical step required to form the CEP group. Thus some structural changes were unrelated to CEP groups and were artificially induced by the synthesis method. In biological studies, the CEP-adducted proteins and peptides failed to activate TLR2 in cell-based assays and in an in vivo TLR2-mediated retinal leukocyte infiltration model. Neither CEP adducts nor TLR agonists were able to induce angiogenesis in a tube formation assay. In vivo, treatment of animals with CEP-adducted protein had no effect on laser-induced choroidal neovascularization. Furthermore, in vivo inactivation of TLR2 by deficiency in Myeloid Differentiation factor 88 (Myd88) had no effect on abrasion-induced corneal neovascularization. Thus the CEP-TLR2 axis, which is implicated in other wound angiogenesis models, does not appear to play a pathological role in a corneal wound angiogenesis model. Collectively, our data do not support the mechanism of action of CEP adducts in TLR2-mediated angiogenesis proposed by others. PMID:25343517

  5. Cocaine-mediated microglial activation involves the ER stress-autophagy axis.

    PubMed

    Guo, Ming-Lei; Liao, Ke; Periyasamy, Palsamy; Yang, Lu; Cai, Yu; Callen, Shannon E; Buch, Shilpa

    2015-01-01

    Cocaine abuse leads to neuroinflammation, which, in turn, contributes to the pathogenesis of neurodegeneration associated with advanced HIV-1 infection. Autophagy plays important roles in both innate and adaptive immune responses. However, the possible functional link between cocaine and autophagy has not been explored before. Herein, we demonstrate that cocaine exposure induced autophagy in both BV-2 and primary rat microglial cells as demonstrated by a dose- and time-dependent induction of autophagy-signature proteins such as BECN1/Beclin 1, ATG5, and MAP1LC3B. These findings were validated wherein cocaine treatment of BV-2 cells resulted in increased formation of puncta in cells expressing either endogenous MAP1LC3B or overexpressing GFP-MAP1LC3B. Specificity of cocaine-induced autophagy was confirmed by treating cells with inhibitors of autophagy (3-MA and wortmannin). Intriguingly, cocaine-mediated induction of autophagy involved upstream activation of 2 ER stress pathways (EIF2AK3- and ERN1-dependent), as evidenced by the ability of the ER stress inhibitor salubrinal to ameliorate cocaine-induced autophagy. In vivo validation of these findings demonstrated increased expression of BECN1, ATG5, and MAP1LC3B-II proteins in cocaine-treated mouse brains compared to untreated animals. Increased autophagy contributes to cocaine-mediated activation of microglia since pretreatment of cells with wortmannin resulted in decreased expression and release of inflammatory factors (TNF, IL1B, IL6, and CCL2) in microglial cells. Taken together, our findings suggest that cocaine exposure results in induction of autophagy that is closely linked with neuroinflammation. Targeting autophagic proteins could thus be considered as a therapeutic strategy for the treatment of cocaine-related neuroinflammation diseases. PMID:26043790

  6. Evidence for the Involvement of p38 MAPK Activation in Barnacle Larval Settlement

    PubMed Central

    He, Li-Sheng; Xu, Ying; Matsumura, Kiyotaka; Zhang, Yu; Zhang, Gen; Qi, Shu-Hua; Qian, Pei-Yuan

    2012-01-01

    The barnacle Balanus ( = Amphibalanus) amphitrite is a major marine fouling animal. Understanding the molecular mechanism of larval settlement in this species is critical for anti-fouling research. In this study, we cloned one isoform of p38 MAPK (Bar-p38 MAPK) from this species, which shares the significant characteristic of containing a TGY motif with other species such as yeast, Drosophila and humans. The activation of p38 MAPK was detected by an antibody that recognizes the conserved dual phosphorylation sites of TGY. The results showed that phospho-p38 MAPK (pp38 MAPK) was more highly expressed at the cyprid stage, particularly in aged cyprids, in comparison to other stages, including the nauplius and juvenile stages. Immunostaining showed that Bar-p38 MAPK and pp38 MAPK were mainly located at the cyprid antennules, and especially the third and fourth segments, which are responsible for substratum exploration during settlement. The expression and localization patterns of Bar-p38 MAPK suggest its involvement in larval settlement. This postulation was also supported by the larval settlement bioassay with the p38 MAPK inhibitor SB203580. Behavioral analysis by live imaging revealed that the larvae were still capable of exploring the surface of the substratum after SB203580 treatment. This shows that the effect of p38 MAPK on larval settlement might be by regulating the secretion of permanent proteinaceous substances. Furthermore, the level of pp38 MAPK dramatically decreased after full settlement, suggesting that Bar-p38 MAPK maybe plays a role in larval settlement rather than metamorphosis. Finally, we found that Bar-p38 MAPK was highly activated when larvae confronted extracts of adult barnacle containing settlement cues, whereas larvae pre-treated with SB203580 failed to respond to the crude adult extracts. PMID:23115639

  7. 10 CFR 2.334 - Implementing hearing schedule for proceeding.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... schedule established by the presiding officer in accordance with 10 CFR 2.332(a) of this part for the... activities in the hearing schedule established by the presiding officer under 10 CFR 2.332(a), or that the... beyond the time specified in the hearing schedule established under 10 CFR 2.332(a). The...

  8. 10 CFR 2.334 - Implementing hearing schedule for proceeding.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... schedule established by the presiding officer in accordance with 10 CFR 2.332(a) of this part for the... activities in the hearing schedule established by the presiding officer under 10 CFR 2.332(a), or that the... beyond the time specified in the hearing schedule established under 10 CFR 2.332(a). The...

  9. 10 CFR 30.70 - Schedule A-Exempt concentrations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... MATERIAL Schedules § 30.70 Schedule A—Exempt concentrations. Element (atomic number) Isotope Col. I Gas...: Many radioisotopes disintegrate into isotopes which are also radioactive. In expressing the concentrations in Schedule A, the activity stated is that of the parent isotope and takes into account...

  10. Schedule shifts, cancer and longevity

    PubMed Central

    Cornélissen, Germaine; Halberg, Julia; Halberg, Franz; de la Pena, Salvador Sanchez; Nelson, Walter; Schwartzkopff, Othild; Stoynev, Alexander; Haus, Erhard

    2008-01-01

    Prompted by a recent report of the possible carcinogenic effect of shiftwork focusing on the disruption of circadian rhythms, we review studies involving shifts in schedule implemented at varying intervals in unicells, insects and mammals, including humans. Results indicate the desirability to account for a broader-than-circadian view. They also suggest the possibility of optimizing schedule shifts by selecting intervals between consecutive shifts associated with potential side-effects such as an increase in cancer risk. Toward this goal, marker rhythmometry is most desirable. The monitoring of blood pressure and heart rate present the added benefit of assessing cardiovascular disease risks resulting not only from an elevated blood pressure but also from abnormal variability in blood pressure and/or heart rate of normotensive as well as hypertensive subjects. PMID:19227006

  11. Current Practice of Public Involvement Activities in Biomedical Research and Innovation: A Systematic Qualitative Review

    PubMed Central

    Lander, Jonas; Hainz, Tobias; Hirschberg, Irene; Strech, Daniel

    2014-01-01

    Background A recent report from the British Nuffield Council on Bioethics associated ‘emerging biotechnologies’ with a threefold challenge: 1) uncertainty about outcomes, 2) diverse public views on the values and implications attached to biotechnologies and 3) the possibility of creating radical changes regarding societal relations and practices. To address these challenges, leading international institutions stress the need for public involvement activities (PIAs). The objective of this study was to assess the state of PIA reports in the field of biomedical research. Methods PIA reports were identified via a systematic literature search. Thematic text analysis was employed for data extraction. Results After filtering, 35 public consultation and 11 public participation studies were included in this review. Analysis and synthesis of all 46 PIA studies resulted in 6 distinguishable PIA objectives and 37 corresponding PIA methods. Reports of outcome translation and PIA evaluation were found in 9 and 10 studies respectively (20% and 22%). The paper presents qualitative details. Discussion The state of PIAs on biomedical research and innovation is characterized by a broad range of methods and awkward variation in the wording of objectives. Better comparability of PIAs might improve the translation of PIA findings into further policy development. PIA-specific reporting guidelines would help in this regard. The modest level of translation efforts is another pointer to the “deliberation to policy gap”. The results of this review could inform the design of new PIAs and future efforts to improve PIA comparability and outcome translation. PMID:25469705

  12. Nanometer Scale Titanium Surface Texturing Are Detected by Signaling Pathways Involving Transient FAK and Src Activations

    PubMed Central

    Zambuzzi, Willian F.; Bonfante, Estevam A.; Jimbo, Ryo; Hayashi, Mariko; Andersson, Martin; Alves, Gutemberg; Takamori, Esther R.; Beltrão, Paulo J.; Coelho, Paulo G.; Granjeiro, José M.

    2014-01-01

    Background It is known that physico/chemical alterations on biomaterial surfaces have the capability to modulate cellular behavior, affecting early tissue repair. Such surface modifications are aimed to improve early healing response and, clinically, offer the possibility to shorten the time from implant placement to functional loading. Since FAK and Src are intracellular proteins able to predict the quality of osteoblast adhesion, this study evaluated the osteoblast behavior in response to nanometer scale titanium surface texturing by monitoring FAK and Src phosphorylations. Methodology Four engineered titanium surfaces were used for the study: machined (M), dual acid-etched (DAA), resorbable media microblasted and acid-etched (MBAA), and acid-etch microblasted (AAMB). Surfaces were characterized by scanning electron microscopy, interferometry, atomic force microscopy, x-ray photoelectron spectroscopy and energy dispersive X-ray spectroscopy. Thereafter, those 4 samples were used to evaluate their cytotoxicity and interference on FAK and Src phosphorylations. Both Src and FAK were investigated by using specific antibody against specific phosphorylation sites. Principal Findings The results showed that both FAK and Src activations were differently modulated as a function of titanium surfaces physico/chemical configuration and protein adsorption. Conclusions It can be suggested that signaling pathways involving both FAK and Src could provide biomarkers to predict osteoblast adhesion onto different surfaces. PMID:24999733

  13. Water-soluble chlorophyll protein is involved in herbivore resistance activation during greening of Arabidopsis thaliana

    PubMed Central

    Boex-Fontvieille, Edouard; Rustgi, Sachin; von Wettstein, Diter; Reinbothe, Steffen; Reinbothe, Christiane

    2015-01-01

    Water-soluble chlorophyll proteins (WSCPs) constitute a small family of unusual chlorophyll (Chl)-binding proteins that possess a Kunitz-type protease inhibitor domain. In Arabidopsis thaliana, a WSCP has been identified, named AtWSCP, that forms complexes with Chl and the Chl precursor chlorophyllide (Chlide) in vitro. AtWSCP exhibits a quite unexpected expression pattern for a Chl binding protein and accumulated to high levels in the apical hook of etiolated plants. AtWSCP expression was negatively light-regulated. Transgenic expression of AtWSCP fused to green fluorescent protein (GFP) revealed that AtWSCP is localized to cell walls/apoplastic spaces. Biochemical assays identified AtWSCP as interacting with RD21 (RESPONSIVE TO DESICCATION 21), a granulin domain-containing cysteine protease implicated in stress responses and defense. Reconstitution experiments showed tight interactions between RD21 and WSCP that were relieved upon Chlide binding. Laboratory feeding experiments with two herbivorous isopod crustaceans, Porcellio scaber (woodlouse) and Armadillidium vulgare (pillbug), identified the apical hook as Achilles’ heel of etiolated plants and that this was protected by RD21 during greening. Because Chlide is formed in the apical hook during seedling emergence from the soil, our data suggest an unprecedented mechanism of herbivore resistance activation that is triggered by light and involves AtWSCP. PMID:26016527

  14. Water-soluble chlorophyll protein is involved in herbivore resistance activation during greening of Arabidopsis thaliana.

    PubMed

    Boex-Fontvieille, Edouard; Rustgi, Sachin; von Wettstein, Diter; Reinbothe, Steffen; Reinbothe, Christiane

    2015-06-01

    Water-soluble chlorophyll proteins (WSCPs) constitute a small family of unusual chlorophyll (Chl)-binding proteins that possess a Kunitz-type protease inhibitor domain. In Arabidopsis thaliana, a WSCP has been identified, named AtWSCP, that forms complexes with Chl and the Chl precursor chlorophyllide (Chlide) in vitro. AtWSCP exhibits a quite unexpected expression pattern for a Chl binding protein and accumulated to high levels in the apical hook of etiolated plants. AtWSCP expression was negatively light-regulated. Transgenic expression of AtWSCP fused to green fluorescent protein (GFP) revealed that AtWSCP is localized to cell walls/apoplastic spaces. Biochemical assays identified AtWSCP as interacting with RD21 (responsive to desiccation 21), a granulin domain-containing cysteine protease implicated in stress responses and defense. Reconstitution experiments showed tight interactions between RD21 and WSCP that were relieved upon Chlide binding. Laboratory feeding experiments with two herbivorous isopod crustaceans, Porcellio scaber (woodlouse) and Armadillidium vulgare (pillbug), identified the apical hook as Achilles' heel of etiolated plants and that this was protected by RD21 during greening. Because Chlide is formed in the apical hook during seedling emergence from the soil, our data suggest an unprecedented mechanism of herbivore resistance activation that is triggered by light and involves AtWSCP. PMID:26016527

  15. Assembly of spaced chromatin involvement of ATP and DNA topoisomerase activity.

    PubMed Central

    Almouzni, G; Méchali, M

    1988-01-01

    Undiluted extracts from eggs or oocytes of Xenopus laevis support the assembly of chromatin with physiologically spaced nucleosomes. Micrococcal nuclease and DNase I digestion experiments show that nucleosome formation as well as supercoiling of circular DNA concomitant to assembly do not require ATP or Mg2+. However these factors are essential for the stability and the physiological spacing of the assembled chromatin. gamma-S-ATP can substitute for ATP in this process. With topoisomers of defined linking number topological interconversions proceed by steps of unity, both in vitro as well as in vivo, indicating that topoisomerase I is dominantly acting in this process. Novobiocin sensitivity occurred only with diluted extracts and was unrelated to an inhibition of topoisomerase II. Finally, nucleosome assembly occurs efficiently on linear DNA although the assembled DNA is less stable than with circular DNA. From these results we propose that mature chromatin is formed in a two-step reaction. In the first step, nucleosome deposition occurs independently of ATP and Mg2+. Thus, nucleosome formation can be uncoupled from their spacing. In this step, topoisomerase activity is involved in the relaxation of the topological constraints generated by chromatin assembly rather than in the process of assembly itself. The second step, requiring ATP and Mg2+, generates properly spaced chromatin. Images PMID:2854062

  16. Protease-Activated Receptor 2 Is Involved in Th2 Responses against Trichinella spiralis Infection

    PubMed Central

    Park, Mi Kyung; Cho, Min Kyoung; Kang, Shin Ae; Park, Hye-Kyung; Kim, Yun Seong; Kim, Ki Uk; Ahn, Soon Cheol; Kim, Dong-Hee

    2011-01-01

    In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection. PMID:22072823

  17. Advanced Reactors Transition Program Resource Loaded Schedule

    SciTech Connect

    BOWEN, W.W.

    1999-11-08

    The Advanced Reactors Transition (ART) Resource Loaded Schedule (RLS) provides a cost and schedule baseline for managing the project elements within the ART Program. The Fast Flux Test Facility (FFTF) activities are delineated through the end of FY 2000, assuming continued standby. The Nuclear Energy (NE) Legacies and Plutonium Recycle Test Reactor (PRTR) activities are delineated through the end of the deactivation process. This document reflects the 1 Oct 1999 baseline.

  18. Advanced Reactors Transition Program Resource Loaded Schedule

    SciTech Connect

    GANTT, D.A.

    2000-01-12

    The Advanced Reactors Transition (ART) Resource Loaded Schedule (RLS) provides a cost and schedule baseline for managing the project elements within the ART Program. The Fast Flux Test Facility (FETF) activities are delineated through the end of FY 2000, assuming continued standby. The Nuclear Energy (NE) Legacies and Plutonium Recycle Test Reactor (PRTR) activities are delineated through the end of the deactivation process. This revision reflects the 19 Oct 1999 baseline.

  19. Scheduling lessons learned from the Autonomous Power System

    NASA Technical Reports Server (NTRS)

    Ringer, Mark J.

    1992-01-01

    The Autonomous Power System (APS) project at NASA LeRC is designed to demonstrate the applications of integrated intelligent diagnosis, control, and scheduling techniques to space power distribution systems. The project consists of three elements: the Autonomous Power Expert System (APEX) for Fault Diagnosis, Isolation, and Recovery (FDIR); the Autonomous Intelligent Power Scheduler (AIPS) to efficiently assign activities start times and resources; and power hardware (Brassboard) to emulate a space-based power system. The AIPS scheduler was tested within the APS system. This scheduler is able to efficiently assign available power to the requesting activities and share this information with other software agents within the APS system in order to implement the generated schedule. The AIPS scheduler is also able to cooperatively recover from fault situations by rescheduling the affected loads on the Brassboard in conjunction with the APEX FDIR system. AIPS served as a learning tool and an initial scheduling testbed for the integration of FDIR and automated scheduling systems. Many lessons were learned from the AIPS scheduler and are now being integrated into a new scheduler called SCRAP (Scheduler for Continuous Resource Allocation and Planning). This paper will service three purposes: an overview of the AIPS implementation, lessons learned from the AIPS scheduler, and a brief section on how these lessons are being applied to the new SCRAP scheduler.

  20. The EUVE proposal database and scheduling system

    NASA Technical Reports Server (NTRS)

    Christian, C.; Olson, E.; Jelinsky, P.; Samuel, M.

    1992-01-01

    The proposal database and scheduling system for the Extreme Ultraviolet Explorer will be described. The proposal database has been implemented to take input for approved observations selected by the EUVE Peer Review Panel and output target information suitable for the scheduling system to digest. The scheduling system is a hybrid of the SPIKE program and EUVE software which checks spacecraft constraints, produces a proposed schedule and selects spacecraft orientations with optimal configurations for acquiring star trackers, etc. This system has been used to schedule the In Orbit Calibration activities that took place this summer, following the EUVE launch in early June 1992. The implemented strategy has implications for the selection of approved targets, which have impacted the Peer Review process. In addition, it will be discussed how the proposal database, founded on Sybase, controls the processing of EUVE Guest Observer data.

  1. Range Scheduling Aid (RSA)

    NASA Technical Reports Server (NTRS)

    Logan, J. R.; Pulvermacher, M. K.

    1991-01-01

    Range Scheduling Aid (RSA) is presented in the form of the viewgraphs. The following subject areas are covered: satellite control network; current and new approaches to range scheduling; MITRE tasking; RSA features; RSA display; constraint based analytic capability; RSA architecture; and RSA benefits.

  2. Surviving Block Scheduling.

    ERIC Educational Resources Information Center

    Haley, Marjorie

    A discussion of block scheduling for second language instruction looks at the advantages and disadvantages and offers some suggestions for classroom management and course organization. It is argued that block scheduling may offer a potential solution to large classes, insufficient time for labs, too little individualized instruction; few…

  3. Block Scheduling Revisited.

    ERIC Educational Resources Information Center

    Queen, J. Allen

    2000-01-01

    Successful block scheduling depends on provision of initial and ongoing instructional training. Teaching strategies should vary and include cooperative learning, the case method, the socratic seminar, synectics, concept attainment, the inquiry method, and simulations. Recommendations for maximizing block scheduling are outlined. (Contains 52…

  4. A Fluid Block Schedule

    ERIC Educational Resources Information Center

    Ubben, Gerald C.

    1976-01-01

    Achieving flexibility without losing student accountability is a challenge that faces every school. With a fluid block schedule, as described here, accountability is maintained without inhibiting flexibility. An additional advantage is that three levels of schedule decision making take some of the pressure off the principal. (Editor)

  5. Scheduling: Seven Period Day

    ERIC Educational Resources Information Center

    Williamson, Ronald

    2010-01-01

    Driven by stable or declining financial resources many school districts are considering the costs and benefits of a seven-period day. While there is limited evidence that any particular scheduling model has a greater impact on student learning than any other, it is clear that the school schedule is a tool that can significantly impact teacher…

  6. Trimester Schedule. Research Brief

    ERIC Educational Resources Information Center

    Education Partnerships, Inc., 2012

    2012-01-01

    Why do a trimester schedule? With the advent of block scheduling, many high schools conducted research on utilizing that plan in a trimester format. There appeared to be three issues that most schools faced: (1) How to provide substantive instructional time that was not fragmented?; (2) How does the school climate contribute positively to…

  7. Space station payload operations scheduling with ESP2

    NASA Technical Reports Server (NTRS)

    Stacy, Kenneth L.; Jaap, John P.

    1988-01-01

    The Mission Analysis Division of the Systems Analysis and Integration Laboratory at the Marshall Space Flight Center is developing a system of programs to handle all aspects of scheduling payload operations for Space Station. The Expert Scheduling Program (ESP2) is the heart of this system. The task of payload operations scheduling can be simply stated as positioning the payload activities in a mission so that they collect their desired data without interfering with other activities or violating mission constraints. ESP2 is an advanced version of the Experiment Scheduling Program (ESP) which was developed by the Mission Integration Branch beginning in 1979 to schedule Spacelab payload activities. The automatic scheduler in ESP2 is an expert system that embodies the rules that expert planners would use to schedule payload operations by hand. This scheduler uses depth-first searching, backtracking, and forward chaining techniques to place an activity so that constraints (such as crew, resources, and orbit opportunities) are not violated. It has an explanation facility to show why an activity was or was not scheduled at a certain time. The ESP2 user can also place the activities in the schedule manually. The program offers graphical assistance to the user and will advise when constraints are being violated. ESP2 also has an option to identify conflict introduced into an existing schedule by changes to payload requirements, mission constraints, and orbit opportunities.

  8. Next Generation CANDU: Conceptual Design for a Short Construction Schedule

    SciTech Connect

    Hopwood, Jerry M.; Love, Ian J.W.; Elgohary, Medhat; Fairclough, Neville

    2002-07-01

    Atomic Energy of Canada Ltd. (AECL) has very successful experience in implementing new construction methods at the Qinshan (Phase III) twin unit CANDU 6 plant in China. This paper examines the construction method that must be implemented during the conceptual design phase of a project if short construction schedules are to be met. A project schedule of 48 months has been developed for the nth unit of NG (Next Generation) CANDU with a 42 month construction period from 1. Concrete to In-Service. An overall construction strategy has been developed involving paralleling project activities that are normally conducted in series. Many parts of the plant will be fabricated as modules and be installed using heavy lift cranes. The Reactor Building (RB), being on the critical path, has been the focus of considerable assessment, looking at alternative ways of applying the construction strategy to this building. A construction method has been chosen which will result in excess of 80% of internal work being completed as modules or as very streamlined traditional construction. This method is being further evaluated as the detailed layout proceeds. Other areas of the plant have been integrated into the schedule and new construction methods are being applied to these so that further modularization and even greater paralleling of activities will be achieved. It is concluded that the optimized construction method is a requirement, which must be implemented through all phases of design to make a 42 month construction schedule a reality. If the construction methods are appropriately chosen, the schedule reductions achieved will make nuclear more competitive. (authors)

  9. Peroxisome proliferator-activated receptor alpha is involved in the regulation of lipid metabolism by ginseng.

    PubMed

    Yoon, Michung; Lee, Hyunghee; Jeong, Sunhyo; Kim, Jung-Jae; Nicol, Christopher J; Nam, Kung Woo; Kim, Moonza; Cho, Byung Goo; Oh, Goo Taeg

    2003-04-01

    1. Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the expression of the key genes involved in lipid metabolism following activation of this receptor by various ligands. Ginseng, a highly valuable medicine in oriental societies, is also reported to modulate lipid metabolism, although the mechanism of its action remains unknown. In order to test our hypothesis that ginseng exerts its effects by altering PPARalpha-mediated pathways, the effects of Korean red ginseng on PPARalpha function and serum lipid profiles were investigated using in vivo and in vitro approaches. 2. In vivo administration of ginseng extract (GE) and ginsenosides (GS) not only inhibited mRNA levels of acyl-CoA oxidase, a rate-limiting enzyme for PPARalpha-mediated peroxisomal fatty acid beta-oxidation, induced by the potent PPARalpha ligand Wy14,643 in a dose- and time-dependent manner, but also inhibited the induction of PPARalpha target genes expected following treatment with Wy14,643. 3. Consistent with the in vivo data, both GE and GS caused dose-dependent decreases in the endogenous expression of a luciferase reporter gene containing the PPAR responsive element (PPRE), while GS significantly decreased the magnitude of reporter gene activation in the presence of Wy14,643. 4. Serological studies demonstrated that, compared with vehicle-treated mice, treatment with GS significantly increased serum concentrations of total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol. Compared to groups treated with Wy14,643 alone, which significantly decreased serum triglyceride and HDL cholesterol levels versus controls, coadministration of either GE or GS with Wy14,643 modestly increased serum triglycerides and HDL cholesterol. 5. These results indicate that the effects of ginseng on serum lipid profiles may be mediated by changes in the expression of PPARalpha target genes, providing the first evidence that in vivo and in vitro treatments of ginseng

  10. Study of the possible mechanisms involved in the mucosal immune system activation by lactic acid bacteria.

    PubMed

    Perdigón, G; Vintiñi, E; Alvarez, S; Medina, M; Medici, M

    1999-06-01

    The induction of a mucosal immune response is not easy due to the development of oral tolerance, but under some conditions, bacteria can activate this immune system. Antigens administered orally can interact with M cells of Peyer's patches or bind to the epithelial cells. We have demonstrated that certain lactic acid bacteria are able to induce specific secretory immunity, and others will enhance the gut inflammatory immune response. The aim of this work was to establish the reason for these different behaviors and to define possible mechanisms involved in the interaction of lactic acid bacteria at the intestinal level. We studied IgA+ and IgM+ B cells comparatively in bronchus and intestine and CD4+ T cells and IgA anti-lactic acid bacteria antibodies in the intestinal fluid, induced by oral administration of Lactobacillus casei, Lb. delbrueckii ssp. bulgaricus, Lb. acidophilus, Lb. plantarum, Lb. rhamnosus, Lactococcus lactis, and Streptococcus salivarius ssp. thermophilus. The increase in the IgA+ B cells in the bronchus means that these lactic acid bacteria were able to induce the IgA cycle by interaction with M cells from Peyer's patches or intestinal epithelial cells. The IgM+ cells increased when the stimulus did not induce the switch from IgM+ to IgA+. The increase in the CD4+ cells suggests interaction of Peyer's patches and enhancement of the B- and T-cell migration. The anti-lactic acid bacteria antibody is related to the processing and presentation of the microorganisms to the immune cells. We demonstrated that Lb. casei and Lb. plantarum were able to interact with Peyer's patch cells and showed an increase in IgA-, CD4+ cells, and antibodies specific for the stimulating strain. Lactobacillus acidophilus induced gut mucosal activation by interaction with the epithelial cells without increase in the immune cells associated with the bronchus. Although Lb. rhamnosus and Strep. salivarius ssp. thermophilus interact with epithelial cells, they also induced

  11. Incremental Scheduling Engines: Cost Savings through Automation

    NASA Technical Reports Server (NTRS)

    Jaap, John; Phillips, Shaun

    2005-01-01

    As humankind embarks on longer space missions farther from home, the requirements and environments for scheduling the activities performed on these missions are changing. As we begin to prepare for these missions it is appropriate to evaluate the merits and applicability of the different types of scheduling engines. Scheduling engines temporally arrange tasks onto a timeline so that all constraints and ob.jectives are met and resources are not over-booked. Scheduling engines used to schedule space missions fall into three general categories: batch, mixed-initiative, and incremental. This paper, presents an assessment of the engine types, a discussion of the impact of human exploration of the moon and Mars on planning and scheduling, and the applicability of the different types of scheduling engines. This paper will pursue the hypothesis that incremental scheduling engines may have a place in the new environment; they have the potential to reduce cost, to improve the satisfaction of those who execute or benefit from a particular timeline (the customers), and to allow astronauts to plan their own tasks and those of their companion robots.

  12. Rural Schooling in Georgia: The Experiences of a Minority Community Service Organization Involved in Local School Decision-Making Activities

    ERIC Educational Resources Information Center

    Lowe, Cynthia Louise Altman

    2010-01-01

    This dissertation study was a descriptive case study of a minority community service organization whose members were actively involved in local school decision-making and activities in a rural Northeast Georgia community. Rural schools face unique challenges in light of current educational trends. To address the challenges, rural schools must…

  13. Understanding the Meaning African-American Men Give to Their Student Leadership Involvement and Engagement Activities in College

    ERIC Educational Resources Information Center

    Brooks, Karl A.

    2012-01-01

    The purpose of this qualitative, phenomenological study was to explore and gain a deeper understanding of the lived experiences and perceptions of African-American (A-A) men who are persisting in college and who demonstrate participation in co-curricular activities defined as student leadership involvement and engagement activities (SLIEA). The…

  14. Active involvement of people with intellectual disabilities in health research - A structured literature review.

    PubMed

    Frankena, Tessa Kim; Naaldenberg, Jenneken; Cardol, Mieke; Linehan, Christine; van Schrojenstein Lantman-de Valk, Henny

    2015-01-01

    Actively involving people with intellectual disabilities (ID) in health research, also known as inclusive health research, is increasingly popular. Currently, insight into experiences of this type of research is scarce. To gain insight into this topic, a structured literature review was conducted focussing on (1) existing theories, (2) inclusive methods, (3) added value and (4) barriers and facilitators. Literature published between January 2000 and January 2014 was included covering keywords related to ID and inclusive health research. Searches were performed in Pubmed, CINAHL, PsycINFO, EMBASE and MEDLINE databases, resulting in 26 included papers. Papers were quality assessed and analysed using qualitative data analysis software. Four theories were often simultaneously addressed: participatory research, emancipatory research, inclusive research and Arnstein's ladder. Barriers and facilitators could be divided into preparing, undertaking and finalising phases of research. Authors indicated that their motivation to conduct inclusive health research was based on demands by policy and funding bodies or was based on ethical considerations (i.e., ethical notions and giving people with ID a voice). Upon completion, authors perceived increased quality and validity of their research and several benefits for stakeholders (i.e., people with ID, researchers and healthcare professionals). Overall, there was consistency in their perception of the most important aspects of inclusive health research. Based on the analysis of included papers, four recommendations of inclusive health research with people with ID were found. Inclusive health research should be: (1) tailoring to the specific study; (2) anticipating all stakeholders; (3) considering its added value; and (4) providing insight into its process. PMID:26280692

  15. Identification of Tyrosine Residues in Constitutively Activated Fibroblast Growth Factor Receptor 3 Involved in Mitogenesis, Stat Activation, and Phosphatidylinositol 3-Kinase Activation

    PubMed Central

    Hart, Kristen C.; Robertson, Scott C.; Donoghue, Daniel J.

    2001-01-01

    Fibroblast growth factor receptor 3 (FGFR3) mutations are frequently involved in human developmental disorders and cancer. Activation of FGFR3, through mutation or ligand stimulation, results in autophosphorylation of multiple tyrosine residues within the intracellular domain. To assess the importance of the six conserved tyrosine residues within the intracellular domain of FGFR3 for signaling, derivatives were constructed containing an N-terminal myristylation signal for plasma membrane localization and a point mutation (K650E) that confers constitutive kinase activation. A derivative containing all conserved tyrosine residues stimulates cellular transformation and activation of several FGFR3 signaling pathways. Substitution of all nonactivation loop tyrosine residues with phenylalanine rendered this FGFR3 construct inactive, despite the presence of the activating K650E mutation. Addition of a single tyrosine residue, Y724, restored its ability to stimulate cellular transformation, phosphatidylinositol 3-kinase activation, and phosphorylation of Shp2, MAPK, Stat1, and Stat3. These results demonstrate a critical role for Y724 in the activation of multiple signaling pathways by constitutively activated mutants of FGFR3. PMID:11294897

  16. Family involvement in music impacts participation of children with cochlear implants in music education and music activities

    PubMed Central

    Driscoll, Virginia; Gfeller, Kate; Tan, Xueli; See, Rachel L.; Cheng, Hsin-Yi; Kanemitsu, Mikiko

    2014-01-01

    Objective Children with cochlear implants (CIs) participate in musical activities in school and daily lives. Considerable variability exists regarding the amount of music involvement and enjoyment. Using the Music Engagement Questionnaire-Preschool/Elementary (MEQ-P/E), we wanted to determine patterns of musical participation and the impact of familial factors on engagement. Methods Parents of 32 children with CIs (16 preschool, 16 elementary) completed a questionnaire regarding the musical involvement of their child with an implant and a normal-hearing (NH) sibling (if one existed). We compared CI children's involvement to that of their NH siblings as well as across groups of children with and without CIs. Correlations between parent ratings of music importance, demographic factors, and involvement of CI and NH children were conducted within and across groups. Results No significant differences were found between children with CIs and NH siblings, meaning children from the same family showed similar levels of musical involvement. When compared at the same developmental stage, no significant differences were found between preschool children with and without CIs. Parents who rated the importance of music as “low” or “middle” had children (NH and CI) who were less involved in music activities. Children whose parents rated music importance as “high” were involved in monthly to weekly music activities with 81.25% reporting daily music listening. Conclusion Despite a less-than-ideal auditory signal for music, preschool and school-aged CI children enjoy and are involved in musical experiences. Families who enjoy and spend a greater amount of time involved in music tend to have children who also engage more actively in music. PMID:25431978

  17. Family involvement in music impacts participation of children with cochlear implants in music education and music activities.

    PubMed

    Driscoll, Virginia; Gfeller, Kate; Tan, Xueli; See, Rachel L; Cheng, Hsin-Yi; Kanemitsu, Mikiko

    2015-05-01

    Objective Children with cochlear implants (CIs) participate in musical activities in school and daily lives. Considerable variability exists regarding the amount of music involvement and enjoyment. Using the Music Engagement Questionnaire-Preschool/Elementary (MEQ-P/E), we wanted to determine patterns of musical participation and the impact of familial factors on engagement. Methods Parents of 32 children with CIs (16 preschool and 16 elementary) completed a questionnaire regarding the musical involvement of their child with an implant and a normal-hearing (NH) sibling (if one existed). We compared CI children's involvement to that of their NH siblings as well as across groups of children with and without CIs. Correlations between parent ratings of music importance, demographic factors, and involvement of CI and NH children were conducted within and across groups. Results No significant differences were found between children with CIs and NH siblings, meaning children from the same family showed similar levels of musical involvement. When compared at the same developmental stage, no significant differences were found between preschool children with and without CIs. Parents who rated the importance of music as 'low' or 'middle' had children (NH and CI) who were less involved in music activities. Children whose parents rated music importance as 'high' were involved in monthly to weekly music activities with 81.25% reporting daily music listening. Conclusion Despite a less-than-ideal auditory signal for music, preschool and school-aged CI children enjoy and are involved in musical experiences. Families who enjoy and spend a greater amount of time involved in music tend to have children who also engage more actively in music. PMID:25431978

  18. Spontaneous activity in the developing gerbil auditory cortex in vivo involves GABAergic transmission

    PubMed Central

    Kotak, Vibhakar C.; Péndola, L. Martín; Rodríguez-Contreras, Adrián

    2012-01-01

    A salient feature of the developing brain is that spontaneous oscillations (SOs) and waves may influence the emergence of synaptic connections. Whilst gamma-amino butyric acid (GABA) produces depolarization and may support SOs in the neurons of developing rodents, it elicits hyperpolarization and diminishes SOs in developing gerbil auditory cortex (ACx). Therefore, we asked whether SOs exist in developing gerbil ACx in vivo and if GABAergic involvement can be manipulated. In vivo extracellular recordings in P3-5 ACx revealed SOs with longer burst durations and shorter inter-event intervals compared to ACx SOs in slices. ACx was then validated by gross anatomical features and lesions created at the in vivo recording site that corresponded with the electrophysiological coordinates of thalamorecipient ACx in slices. Further, NeuroVue Red, a lipophilic dye loaded at the in vivo recording sites, stained anatomically identifiable fiber tracks between the ACx and the auditory thalamus, medial geniculate body (MG). Separately, to chronically perturb GABAergic role in SOs, P2-5 pups were administered daily with GABAA receptor blocker, bicuculline (BIC). We then recorded from P14-17 ACx neurons in slices generated after hearing onset. ACx neurons from BIC-administered pups exhibited spontaneous action potentials in contrast to subthreshold synaptic potentials in neurons from sham-injected animals. Finally, to elucidate whether the gap junction blocker mefloquine (MFQ) previously shown to dampen ACx SOs in slices affected GABAergic transmission, MFQ was acutely applied in P3-5 slices while spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded. Whereas MFQ increased the amplitude and frequency of sIPSCs in ACx neurons, the broad-spectrum gap junction blocker carbenoxolone decreased sIPSC amplitudes only. Together, we show that P2-5 gerbil ACx can endogenously generate SOs in vivo. Persistence of activity in ACx in P14-17 slices from pups administered with BIC at

  19. Differential Involvement of Amygdala and Cortical NMDA Receptors Activation upon Encoding in Odor Fear Memory

    ERIC Educational Resources Information Center

    Hegoburu, Chloé; Parrot, Sandrine; Ferreira, Guilaume; Mouly, Anne-Marie

    2014-01-01

    Although the basolateral amygdala (BLA) plays a crucial role for the acquisition of fear memories, sensory cortices are involved in their long-term storage in rats. However, the time course of their respective involvement has received little investigation. Here we assessed the role of the glutamatergic N-methyl-D-aspartate (NMDA) receptors in the…

  20. Involving Parents of Young Children in Science, Math and Literacy Activities.

    ERIC Educational Resources Information Center

    Landerholm, Elizabeth; And Others

    A summer parent involvement project was set up in a Chicago inner city public school in a Hispanic neighborhood. The eight-session program was intended to help parents: (1) become involved with the school program by becoming comfortable with the school setting; (2) enjoy reading and writing and replicate these experiences with their children; (3)…

  1. Mixed-Integer Formulations for Constellation Scheduling

    NASA Astrophysics Data System (ADS)

    Valicka, C.; Hart, W.; Rintoul, M.

    Remote sensing systems have expanded the set of capabilities available for and critical to national security. Cooperating, high-fidelity sensing systems and growing mission applications have exponentially increased the set of potential schedules. A definitive lack of advanced tools places an increased burden on operators, as planning and scheduling remain largely manual tasks. This is particularly true in time-critical planning activities where operators aim to accomplish a large number of missions through optimal utilization of single or multiple sensor systems. Automated scheduling through identification and comparison of alternative schedules remains a challenging problem applicable across all remote sensing systems. Previous approaches focused on a subset of sensor missions and do not consider ad-hoc tasking. We have begun development of a robust framework that leverages the Pyomo optimization modeling language for the design of a tool to assist sensor operators planning under the constraints of multiple concurrent missions and uncertainty. Our scheduling models have been formulated to address the stochastic nature of ad-hoc tasks inserted under a variety of scenarios. Operator experience is being leveraged to select appropriate model objectives. Successful development of the framework will include iterative development of high-fidelity mission models that consider and expose various schedule performance metrics. Creating this tool will aid time-critical scheduling by increasing planning efficiency, clarifying the value of alternative modalities uniquely provided by multi-sensor systems, and by presenting both sets of organized information to operators. Such a tool will help operators more quickly and fully utilize sensing systems, a high interest objective within the current remote sensing operations community. Preliminary results for mixed-integer programming formulations of a sensor scheduling problem will be presented. Assumptions regarding sensor geometry

  2. NASA Schedule Management Handbook

    NASA Technical Reports Server (NTRS)

    2011-01-01

    The purpose of schedule management is to provide the framework for time-phasing, resource planning, coordination, and communicating the necessary tasks within a work effort. The intent is to improve schedule management by providing recommended concepts, processes, and techniques used within the Agency and private industry. The intended function of this handbook is two-fold: first, to provide guidance for meeting the scheduling requirements contained in NPR 7120.5, NASA Space Flight Program and Project Management Requirements, NPR 7120.7, NASA Information Technology and Institutional Infrastructure Program and Project Requirements, NPR 7120.8, NASA Research and Technology Program and Project Management Requirements, and NPD 1000.5, Policy for NASA Acquisition. The second function is to describe the schedule management approach and the recommended best practices for carrying out this project control function. With regards to the above project management requirements documents, it should be noted that those space flight projects previously established and approved under the guidance of prior versions of NPR 7120.5 will continue to comply with those requirements until project completion has been achieved. This handbook will be updated as needed, to enhance efficient and effective schedule management across the Agency. It is acknowledged that most, if not all, external organizations participating in NASA programs/projects will have their own internal schedule management documents. Issues that arise from conflicting schedule guidance will be resolved on a case by case basis as contracts and partnering relationships are established. It is also acknowledged and understood that all projects are not the same and may require different levels of schedule visibility, scrutiny and control. Project type, value, and complexity are factors that typically dictate which schedule management practices should be employed.

  3. The Theory of Active Involvement: Processes Underlying Interventions that Engage Adolescents in Message Planning and/or Production

    PubMed Central

    Greene, Kathryn

    2013-01-01

    Adolescence is a time of increased risk-taking and recent intervention strategies have included adolescents planning or producing anti-risk messages for their peers. Although these projects may generate enthusiasm, we know little about message planning or production as a strategy for changing adolescent decision-making and behavior. The paper articulates the Theory of Active Involvement (TAI) to describe and explain the processes through which these active involvement interventions influence adolescents. TAI is based on social cognitive theory’s notion of self-regulation and examines multiple perspective-taking and activating the self-reflection processes. The theory specifically describes the process of cognitive changes experienced by participants in active involvement interventions. The sequence is conceptualized as starting when engagement with the intervention (arousal and involvement) produces skill and knowledge gains (immediate outcomes) that lead to reflection (perceived discrepancy) and then other cognitions (expectancies, norms, intentions), with the ultimate outcome being behavior change. Engaging the target audience in a process of self-reflection is conceptualized as the crucial ingredient for meaningful and sustainable change in cognitions and behavior. This paper provides valuable insight into how active involvement strategies function and how to best design these interventions, particularly those targeting adolescents. PMID:23980581

  4. Combining active farmer involvement with detailed farm data in Denmark: a promising method for achieving water framework directive targets?

    PubMed

    Wright, Stuart A L; Jacobsen, Brian H

    2010-01-01

    The Water Framework Directive (WFD) encourages active involvement during its implementation, although no specific participatory methods are suggested, whilst implementing the target-oriented Directive will require detailed agri-environmental data at catchment and farm level. The paper is a case study of the Danish AGWAplan project, which actively involved farmers in the selection of measures to reduce diffuse nutrient pollution at farm and catchment level, thereby providing an example of how active involvement might be operationalised. Active involvement has been identified as being of central importance to the success of the WFD. The project also entailed the accumulation of extensive agri-environmental data. The aim of the paper is to evaluate AGWAplan to establish the extent to which its expected objectives have been achieved and how, and to determine whether the project approach might facilitate WFD goals if implemented in forthcoming river basin management plans (RBMPs). AGWAplan resulted in advantageous outcomes, including win-win solutions to reduce nutrient leaching and greater acceptance of policy, although the original reduction targets where not fully reached. The paper concludes that actively involving farmers in a similar manner in RBMPs may make an important contribution to the implementation of the WFD, although caveats regarding its potential for transfer to other areas are identified. PMID:20453337

  5. Identification and Functions of Amino Acid Residues in PotB and PotC Involved in Spermidine Uptake Activity*

    PubMed Central

    Higashi, Kyohei; Sakamaki, Yoshiharu; Herai, Emiko; Demizu, Risa; Uemura, Takeshi; Saroj, Sunil D.; Zenda, Risa; Terui, Yusuke; Nishimura, Kazuhiro; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

    2010-01-01

    Amino acid residues on PotB and PotC involved in spermidine uptake were identified by random and site-directed mutagenesis. It was found that Trp8, Tyr43, Trp100, Leu110, and Tyr261 in PotB and Trp46, Asp108, Glu169, Ser196, Asp198, and Asp199 in PotC were strongly involved in spermidine uptake and that Tyr160, Glu172, and Leu274 in PotB and Tyr19, Tyr88, Tyr148, Glu160, Leu195, and Tyr211 in PotC were moderately involved in spermidine uptake. Among 11 amino acid residues that were strongly involved in spermidine uptake, Trp8 in PotB was important for insertion of PotB and PotC into membranes. Tyr43, Trp100, and Leu110 in PotB and Trp46, Asp108, Ser196, and Asp198 in PotC were found to be involved in the interaction with PotD. Leu110 and Tyr261 in PotB and Asp108, Asp198, and Asp199 in PotC were involved in the recognition of spermidine, and Trp100 and Tyr261 in PotB and Asp108, Glu169, and Asp198 in PotC were involved in ATPase activity of PotA. Accordingly, Trp100 in PotB was involved in both PotD recognition and ATPase activity, Leu110 in PotB was involved in both PotD and spermidine recognition, and Tyr261 in PotB was involved in both spermidine recognition and ATPase activity. Asp108 and Asp198 in PotC were involved in PotD and spermidine recognition as well as ATPase activity. These results suggest that spermidine passage from PotD to the cytoplasm is coupled to the ATPase activity of PotA through a structural change of PotA by its ATPase activity. PMID:20937813

  6. Character Development within Youth Development Programs: Exploring Multiple Dimensions of Activity Involvement.

    PubMed

    Lynch, Alicia Doyle; Ferris, Kaitlyn A; Burkhard, Brian; Wang, Jun; Hershberg, Rachel M; Lerner, Richard M

    2016-03-01

    We examined links among three dimensions of youth involvement (intensity, duration, and engagement) in Boy Scouts of America (BSA), an international out-of-school time (OST) youth development program designed to promote moral and performance character in boys. Using data from 737 youth and their parents who participated in one of 40 BSA program sites (commonly referred to as "packs"), we first considered how individual- and pack-level measures of program involvement were differentially linked with character development. Next, we examined whether pack-level involvement characteristics moderate individual-level involvement characteristics, hypothesizing that highly involved packs would serve to further enhance the positive effects of high levels of individual involvement. Results indicated engagement was the strongest, most frequent predictor of increases in both moral and performance character. Although there were no direct effects of pack-level intensity, duration, or engagement, the effects of individual-level engagement were moderated by pack-level engagement, suggesting that the largest increases in moral and performance character occurred among highly engaged youth who were enrolled in highly engaged packs. These results highlight the need to examine multiple dimensions of OST program involvement simultaneously, and suggest that strengthening youth engagement in programming may provide a means for enhancing the positive effects of high-quality youth programming. PMID:27217313

  7. Culture perfusion schedules influence the metabolic activity and granulocyte-macrophage colony-stimulating factor production rates of human bone marrow stromal cells.

    PubMed

    Caldwell, J; Palsson, B O; Locey, B; Emerson, S G

    1991-05-01

    The metabolic function and GM-CSF production rates of adherent human bone marrow stromal cells were investigated as functions of medium and serum feeding rates. A range of medium exchange schedules was studied, ranging from a typical Dexter culture protocol of one weekly medium exchange to a full media exchange daily, which more closely approximates what bone marrow cells experience in situ. Glucose consumption was found to be significantly higher at full daily exchange rate than at any other exchange schedule examined. However, the lactate yield on glucose was a constant, at 1.8 mol/mol, under all conditions considered. Differential serum vs. medium exchange experiment showed that both serum supply and medium nutrients were responsible for the altered behavior at high exchange rates. Glutamine consumption was found to be insignificant under all culture conditions examined. A change in exchange schedule from 50% daily medium exchange to full daily medium exchange after 14 days of culture was found to result in a transient production of GM-CSF and a change in metabolic behavior to resemble that of cultures which had full daily exchange from day one. These results suggest that both stromal cell metabolism and GM-CSF production are sensitive to medium exchange schedules. Taken together, the data presented indicate that attempts to model the function of human bone marrow in vitro may be well served by beginning with medium exchange schedules that more closely mimic the in vivo physiologic state of bone marrow. PMID:2040665

  8. Ada and cyclic runtime scheduling

    NASA Technical Reports Server (NTRS)

    Hood, Philip E.

    1986-01-01

    An important issue that must be faced while introducing Ada into the real time world is efficient and prodictable runtime behavior. One of the most effective methods employed during the traditional design of a real time system is the cyclic executive. The role cyclic scheduling might play in an Ada application in terms of currently available implementations and in terms of implementations that might be developed especially to support real time system development is examined. The cyclic executive solves many of the problems faced by real time designers, resulting in a system for which it is relatively easy to achieve approporiate timing behavior. Unfortunately a cyclic executive carries with it a very high maintenance penalty over the lifetime of the software that is schedules. Additionally, these cyclic systems tend to be quite fragil when any aspect of the system changes. The findings are presented of an ongoing SofTech investigation into Ada methods for real time system development. The topics covered include a description of the costs involved in using cyclic schedulers, the sources of these costs, and measures for future systems to avoid these costs without giving up the runtime performance of a cyclic system.

  9. Staying in or Moving Away from Structured Activities: Explanations Involving Parents and Peers

    ERIC Educational Resources Information Center

    Persson, Andreas; Kerr, Margaret; Stattin, Hakan

    2007-01-01

    Adolescent participation in structured activities, meaning those with adult leaders, regular meetings, and skill-building activities, is related to good adjustment. Participation in unstructured, unsupervised, peer-oriented activities is related to poor adjustment. Structured activity participation is high in early adolescence and then declines,…

  10. Personal involvement is related to increased search motivation and associated with activity in left BA44-a pilot study.

    PubMed

    Schaefer, Michael; Rumpel, Franziska; Sadrieh, Abdolkarim; Reimann, Martin; Denke, Claudia

    2015-01-01

    Numerous studies explore consumer perception of brands in a more or less passive way. This may still be representative for many situations or decisions we make each day. Nevertheless, sometimes we often actively search for and use information to make informed and reasoned choices, thus implying a rational and thinking consumer. Researchers suggested describing this distinction as low relative to high involvement consumer behavior. Although the involvement concept has been widely used to explain consumer behavior, behavioral and neural correlates of this concept are poorly understood. The current study aims to describe a behavioral measure that is associated with high involvement, the length of search behavior. A second aim of this study was to explore brain activations associated with involvement by employing functional magnetic resonance imaging (fMRI). We presented participants information cues for different products and told them that they had to answer questions with respect to these products at the end of the experiment. Participants were free to stop the information search if they think they gathered enough information or to continue with collecting information. Behavioral results confirmed our hypothesis of a relationship between searching behavior and personal involvement by demonstrating that the length of search correlated significantly with the degree of personal involvement of the participants. fMRI data revealed that personal involvement was associated with activation in BA44. Since this brain region is known to be involved in semantic memory, the results of this pilot study suggest that high involvement consumer behavior may be linked to cognitive load and attention towards a product. PMID:25859200

  11. Scheduling and Utilization.

    ERIC Educational Resources Information Center

    Blakesley, James F.

    1982-01-01

    College scheduling system and operating procedure objectives influence efficient use of resources. Theoretical and practical considerations are outlined, including a step-by-step assessment of an institution's enrollment capacity and discussion of centralized or reassignable classrooms. (Author/MSE)

  12. Childhood Vaccine Schedule

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Childhood Vaccine Schedule Past Issues / Spring 2008 Table of Contents ... please turn Javascript on. When to Vaccinate What Vaccine Why Birth (or any age if not previously ...

  13. Schedule Risk Assessment

    NASA Technical Reports Server (NTRS)

    Smith, Grego

    2004-01-01

    Schedule Risk Assessment (SRA) determines the probability of finishing on or before a given point in time. This viewgraph presentation introduces the prerequisites, probability distribution curves, special conditions, calculations, and results analysis for SRA.

  14. Distributed network scheduling

    NASA Technical Reports Server (NTRS)

    Clement, Bradley J.; Schaffer, Steven R.

    2005-01-01

    We investigate missions where communications resources are limited, requiring autonomous planning and execution. Unlike typical networks, spacecraft networks are also suited to automated planning and scheduling because many communications can be planned in advance.

  15. Initial Hardware Development Schedule

    NASA Technical Reports Server (NTRS)

    Culpepper, William X.

    1991-01-01

    The hardware development schedule for the Common Lunar Lander's (CLLs) tracking system is presented. Among the topics covered are the following: historical perspective, solution options, industry contacts, and the rationale for selection.

  16. Prototype resupply scheduler

    NASA Technical Reports Server (NTRS)

    Tanner, Steve; Hughes, Angi; Byrd, Jim

    1987-01-01

    Resupply scheduling for the Space Station presents some formidable logistics problems. One of the most basic problems is assigning supplies to a series of shuttle resupply missions. A prototype logistics expert system which constructs resupply schedules was developed. This prototype is able to reconstruct feasible resupply plans. In addition, analysts can use the system to evaluate the impact of adding, deleting or modifying launches, cargo space, experiments, etc.

  17. Video Games and Children: Effects on Leisure Activities, Schoolwork, and Peer Involvement.

    ERIC Educational Resources Information Center

    Creasey, Gary L; Myers, Barbara J

    1986-01-01

    Measures the indirect effect a home video system has on children's leisure activities, school work, and peer contacts. Concludes that owning a video game does not greatly alter a child's activities. (HOD)

  18. A Picture-Based Activity Schedule Intervention to Teach Adults with Mild Intellectual Disability to Use an iPad during a Leisure Activity

    ERIC Educational Resources Information Center

    Chan, Jeffrey Michael; Lambdin, Lindsay; Graham, Kimberly; Fragale, Christina; Davis, Tonya

    2014-01-01

    Individuals with developmental disabilities have limited opportunities to participate in leisure activities, frequently due to lack of skills. The purpose of the current study was to teach three adults diagnosed with mild intellectual disability to use an iPad in the context of playing the video game Angry Birds. We used an adapted multiple…

  19. Involvement in Extracurricular Activities: Identifying Differences in Perceptions of School Climate

    ERIC Educational Resources Information Center

    Martinez, Andrew; Coker, Crystal; McMahon, Susan D.; Cohen, Jonathan; Thapa, Amrit

    2016-01-01

    Many youth participate in extracurricular activities, and research has linked activity participation with school engagement and academic success. Social-ecological theory suggests that the social contexts of different types of extracurricular activities may differentially affect student outcomes. Yet, there is scant research examining the relation…

  20. Parental Involvement in Active Transport to School Initiatives: A Multi-Site Case Study

    ERIC Educational Resources Information Center

    Eyler, Amy; Baldwin, Julie; Carnoske, Cheryl; Nickelson, Jan; Troped, Philip; Steinman, Lesley; Pluto, Delores; Litt, Jill; Evenson, Kelly; Terpstra, Jennifer; Brownson, Ross; Schmid, Thomas

    2008-01-01

    Background: Increasing physical activity in youth is a recommended approach to curbing the childhood obesity epidemic. One way to help increase children's daily activity is to promote active transportation to and from school (ATS). Purpose: The purpose of this case study was to explore parental perception of, and participation in, ATS initiatives.…

  1. Reducing effect of saikosaponin A, an active ingredient of Bupleurum falcatum, on alcohol self-administration in rats: Possible involvement of the GABAB receptor.

    PubMed

    Maccioni, Paola; Lorrai, Irene; Carai, Mauro A M; Riva, Antonella; Morazzoni, Paolo; Mugnaini, Claudia; Corelli, Federico; Gessa, Gian Luigi; Colombo, Giancarlo

    2016-05-16

    Recent studies demonstrated that treatment with saikosaponin A (SSA) - an active ingredient of the medicinal herb, Bupleurum falcatum L. - selectively suppressed, likely via a GABAB receptor-mediated mechanism, intravenous self-administration of morphine and cocaine in rats [Yoon et al., 2012; 2013]. The present study was designed to investigate whether the capacity of SSA to suppress morphine and cocaine self-administration extends to oral alcohol self-administration. To this end, selectively bred Sardinian alcohol-preferring (sP) rats were trained to lever-respond on a Fixed Ratio (FR) 4 (FR4) schedule of reinforcement for alcohol (15%, v/v) in daily 30-min sessions. Once responding had stabilized, rats were tested under the FR4 (measure of alcohol reinforcing properties) and Progressive Ratio (PR; measure of alcohol motivational properties) schedules of reinforcement. The possible involvement of the GABAB receptor system was investigated testing the effect of (a) pretreatment with the GABAB receptor antagonist, SCH50911, and (b) combined treatment with the positive allosteric modulator of the GABAB receptor, GS39783. Treatment with SSA (0, 0.25, 0.5, and 1mg/kg, i.p.) markedly reduced lever-responding for alcohol, amount of self-administered alcohol, and breakpoint for alcohol (defined as the lowest response requirement not achieved in the PR experiment). Pretreatment with 2mg/kg SCH50911 (i.p.) resulted in a partial blockade of the reducing effect of 0.5mg/kg SSA on lever-responding for alcohol and amount of self-administered alcohol. Combination of per se ineffective doses of GS39783 (5mg/kg, i.g.) and SSA (0.1mg/kg, i.p.) reduced lever-responding for alcohol and amount of self-administered alcohol. These results (a) extend to alcohol self-administration the capacity of SSA to suppress morphine and cocaine self-administration in rats and (b) suggest that the GABAB receptor system is likely part of the neural substrate underlying the reducing effect of SSA on

  2. JWST planning and scheduling operations and concepts

    NASA Astrophysics Data System (ADS)

    Kinzel, Wayne M.

    2010-07-01

    The James Webb Space Telescope (JWST) will be a large infrared space observatory in orbit about the Sun-Earth second Lagrange Point. This paper provides an overview of the expected operational requirements imposed by the observatory's basic science activities (imaging, spectroscopy, coronography) and the operational issues associated with interleaving periodic engineering activities (Wave Front Sensing & Control activities, Momentum Unloads, and orbit Station Keeping) with the science observations. The planning and scheduling operations must maximize the overall science integration time while meeting the mission and observer specified constraints. The "Observation," "Visit," and Observation Template constructs are explained in the context of providing an interface to the Observer that provides the ability to specify complex observations, such as mosaics and cluster targets, while also minimizing specification errors and allowing planning and scheduling flexibility of the observations. The expected nominal planning and scheduling process including the creation and maintenance of the Long Range Plan (~1.25 year duration), the Short Term Schedules (~ three weeks), and the on-board Observation Plan (< 10 days) is described. The event-driven on-board operations of JWST and how the planning and scheduling process monitors and reacts to the onboard execution of the Observation Plan are described. Finally, the methods employed to allow for robust interfacing of scheduled real-time operations (for example, Station Keeping) with the Observation Plan and unplanned, but expected, modifications to the Observation Plan (for example, Target of Opportunity) are described.

  3. Relaxin activates peroxisome proliferator-activated receptor γ (PPARγ) through a pathway involving PPARγ coactivator 1α (PGC1α).

    PubMed

    Singh, Sudhir; Simpson, Ronda L; Bennett, Robert G

    2015-01-01

    Relaxin activation of its receptor RXFP1 triggers multiple signaling pathways. Previously, we have shown that relaxin activates PPARγ transcriptional activity in a ligand-independent manner, but the mechanism for this effect was unknown. In this study, we examined the signaling pathways of downstream of RXFP1 leading to PPARγ activation. Using cells stably expressing RXFP1, we found that relaxin regulation of PPARγ activity requires accumulation of cAMP and subsequent activation of cAMP-dependent protein kinase (PKA). The activated PKA subsequently phosphorylated cAMP response element-binding protein (CREB) at Ser-133 to activate it directly, as well as indirectly through mitogen activated protein kinase p38 MAPK. Activated CREB was required for relaxin stimulation of PPARγ activity, while there was no evidence for a role of the nitric oxide or ERK MAPK pathways. Relaxin increased the mRNA and protein levels of the coactivator protein PGC1α, and this effect was dependent on PKA, and was completely abrogated by a dominant-negative form of CREB. This mechanism was confirmed in a hepatic stellate cell line stably that endogenously expresses RXFP1. Reduction of PGC1α levels using siRNA diminished the regulation of PPARγ by relaxin. These results suggest that relaxin activates the cAMP/PKA and p38 MAPK pathways to phosphorylate CREB, resulting in increased PGC1α levels. This provides a mechanism for the ligand-independent activation of PPARγ in response to relaxin. PMID:25389293

  4. Relaxin Activates Peroxisome Proliferator-activated Receptor γ (PPARγ) through a Pathway Involving PPARγ Coactivator 1α (PGC1α)*

    PubMed Central

    Singh, Sudhir; Simpson, Ronda L.; Bennett, Robert G.

    2015-01-01

    Relaxin activation of its receptor RXFP1 triggers multiple signaling pathways. Previously, we have shown that relaxin activates PPARγ transcriptional activity in a ligand-independent manner, but the mechanism for this effect was unknown. In this study, we examined the signaling pathways of downstream of RXFP1 leading to PPARγ activation. Using cells stably expressing RXFP1, we found that relaxin regulation of PPARγ activity requires accumulation of cAMP and subsequent activation of cAMP-dependent protein kinase (PKA). The activated PKA subsequently phosphorylated cAMP response element-binding protein (CREB) at Ser-133 to activate it directly, as well as indirectly through mitogen activated protein kinase p38 MAPK. Activated CREB was required for relaxin stimulation of PPARγ activity, while there was no evidence for a role of the nitric oxide or ERK MAPK pathways. Relaxin increased the mRNA and protein levels of the coactivator protein PGC1α, and this effect was dependent on PKA, and was completely abrogated by a dominant-negative form of CREB. This mechanism was confirmed in a hepatic stellate cell line stably that endogenously expresses RXFP1. Reduction of PGC1α levels using siRNA diminished the regulation of PPARγ by relaxin. These results suggest that relaxin activates the cAMP/PKA and p38 MAPK pathways to phosphorylate CREB, resulting in increased PGC1α levels. This provides a mechanism for the ligand-independent activation of PPARγ in response to relaxin. PMID:25389293

  5. 15 CFR Supplement No. 2 to Part 712 - Deadlines for Submission of Schedule 1 Declarations, Advance Notifications, Reports, and Amendments

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1...: § 712.7(a) —15 calendar days after change in information. —Company information: § 712.7(c) —30 calendar days after change in information. —Post-inspection letter: § 712.7(d) —45 calendar days after...

  6. 15 CFR Supplement No. 2 to Part 712 - Deadlines for Submission of Schedule 1 Declarations, Advance Notifications, Reports, and Amendments

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1...: § 712.7(a) —15 calendar days after change in information. —Company information: § 712.7(c) —30 calendar days after change in information. —Post-inspection letter: § 712.7(d) —45 calendar days after...

  7. 15 CFR Supplement No. 2 to Part 712 - Deadlines for Submission of Schedule 1 Declarations, Advance Notifications, Reports, and Amendments

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1...: § 712.7(a) —15 calendar days after change in information. —Company information: § 712.7(c) —30 calendar days after change in information. —Post-inspection letter: § 712.7(d) —45 calendar days after...

  8. 15 CFR 713.3 - Annual declaration and reporting requirements for exports and imports of Schedule 2 chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... (22 CFR parts 120 through130)). (c) Declaration and reporting requirements—(1) Annual declaration on... Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS § 713.3...

  9. 15 CFR 713.3 - Annual declaration and reporting requirements for exports and imports of Schedule 2 chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... (22 CFR parts 120 through130)). (c) Declaration and reporting requirements—(1) Annual declaration on... Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS § 713.3...

  10. 15 CFR 713.3 - Annual declaration and reporting requirements for exports and imports of Schedule 2 chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... (22 CFR parts 120 through130)). (c) Declaration and reporting requirements—(1) Annual declaration on... Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS § 713.3...

  11. 15 CFR 713.3 - Annual declaration and reporting requirements for exports and imports of Schedule 2 chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... (22 CFR parts 120 through130)). (c) Declaration and reporting requirements—(1) Annual declaration on... Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS § 713.3...

  12. 15 CFR 713.3 - Annual declaration and reporting requirements for exports and imports of Schedule 2 chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... (22 CFR parts 120 through130)). (c) Declaration and reporting requirements—(1) Annual declaration on... Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS § 713.3...

  13. Unique Residues Involved in Activation of the Multitasking Protease/Chaperone HtrA from Chlamydia trachomatis

    PubMed Central

    Huston, Wilhelmina M.; Tyndall, Joel D. A.; Lott, William B.; Stansfield, Scott H.; Timms, Peter

    2011-01-01

    DegP, a member of the HtrA family of proteins, conducts critical bacterial protein quality control by both chaperone and proteolysis activities. The regulatory mechanisms controlling these two distinct activities, however, are unknown. DegP activation is known to involve a unique mechanism of allosteric binding, conformational changes and oligomer formation. We have uncovered a novel role for the residues at the PDZ1:protease interface in oligomer formation specifically for chaperone substrates of Chlamydia trachomatis HtrA (DegP homolog). We have demonstrated that CtHtrA proteolysis could be activated by allosteric binding and oligomer formation. The PDZ1 activator cleft was required for the activation and oligomer formation. However, unique to CtHtrA was the critical role for residues at the PDZ1:protease interface in oligomer formation when the activator was an in vitro chaperone substrate. Furthermore, a potential in vivo chaperone substrate, the major outer membrane protein (MOMP) from Chlamydia, was able to activate CtHtrA and induce oligomer formation. Therefore, we have revealed novel residues involved in the activation of CtHtrA which are likely to have important in vivo implications for outer membrane protein assembly. PMID:21931748

  14. Unique residues involved in activation of the multitasking protease/chaperone HtrA from Chlamydia trachomatis.

    PubMed

    Huston, Wilhelmina M; Tyndall, Joel D A; Lott, William B; Stansfield, Scott H; Timms, Peter

    2011-01-01

    DegP, a member of the HtrA family of proteins, conducts critical bacterial protein quality control by both chaperone and proteolysis activities. The regulatory mechanisms controlling these two distinct activities, however, are unknown. DegP activation is known to involve a unique mechanism of allosteric binding, conformational changes and oligomer formation. We have uncovered a novel role for the residues at the PDZ1:protease interface in oligomer formation specifically for chaperone substrates of Chlamydia trachomatis HtrA (DegP homolog). We have demonstrated that CtHtrA proteolysis could be activated by allosteric binding and oligomer formation. The PDZ1 activator cleft was required for the activation and oligomer formation. However, unique to CtHtrA was the critical role for residues at the PDZ1:protease interface in oligomer formation when the activator was an in vitro chaperone substrate. Furthermore, a potential in vivo chaperone substrate, the major outer membrane protein (MOMP) from Chlamydia, was able to activate CtHtrA and induce oligomer formation. Therefore, we have revealed novel residues involved in the activation of CtHtrA which are likely to have important in vivo implications for outer membrane protein assembly. PMID:21931748

  15. Enzymatic activation of autotaxin by divalent cations without EF-hand loop region involvement.

    PubMed

    Lee, J; Jung, I D; Nam, S W; Clair, T; Jeong, E M; Hong, S Y; Han, J W; Lee, H W; Stracke, M L; Lee, H Y

    2001-07-15

    Autotaxin (ATX) is a recently described member of the nucleotide pyrophosphatase/phosphodiesterase (NPP) family of proteins with potent tumor cell motility-stimulating activity. Like other NPPs, ATX is a glycoprotein with peptide sequences homologous to the catalytic site of bovine intestinal alkaline phosphodiesterase (PDE) and the loop region of an EF-hand motif. The PDE active site of ATX has been associated with the motility-stimulating activity of ATX. In this study, we examined the roles of the EF-hand loop region and of divalent cations on the enzymatic activities of ATX. Ca(2+) or Mg(2+) was each demonstrated to increase the PDE activity of ATX in a concentration-dependent manner, whereas incubation of ATX with chelating agents abolished this activity, indicating a requirement for divalent cations. Non-linear regression analysis of enzyme kinetic data indicated that addition of these divalent cations increases reaction velocity predominantly through an effect on V(max.) Three mutant proteins, Ala(740)-, Ala(742)-, and Ala(751)-ATX, in the EF-hand loop region of ATX had enzymatic activity comparable to that of the wild-type protein. A deletion mutation of the entire loop region resulted in slightly reduced PDE activity but normal motility-stimulating activity. However, the PDE activity of this same deletion mutant remained sensitive to augmentation by cations, strongly implying that cations exert their effect by interactions outside of the EF-hand loop region. PMID:11389881

  16. Examining Parent Involvement Activities in Two Immigrant-Impacted Schools: A Comparative Case Study

    ERIC Educational Resources Information Center

    Marquez, Amalia

    2012-01-01

    K-12 schools with large immigrant populations face a myriad of challenges, including low academic achievement and high dropout rates of Latino students. Parental involvement is a practical strategy in positively influencing student outcomes along the K-12 continuum. To this end, it is essential that immigrant impacted schools work together with…

  17. Parent Advocacy: Now More Than Ever Active Involvement in Educational Decisions.

    ERIC Educational Resources Information Center

    Ammer, Jerome J.; Littleton, Barbara Rhein

    Questionnaires were completed by 217 parents of handicapped children to determine their present level of involvement and their desired participation in the education process. The sample (a rural population in central West Virginia, a suburban population in affluent school districts on Long Island, New York, and a city population from a mixed set…

  18. Undergraduate Involvement in Extracurricular Activities and Leadership Development in College of Agriculture and Life Sciences Students

    ERIC Educational Resources Information Center

    Foreman, Elizabeth A.; Retallick, Michael S.

    2012-01-01

    The purpose of this study was to identify and describe experiences of undergraduate extracurricular involvement that result in increased leadership development. Senior students in the College of Agriculture and Life Sciences at Iowa State University completed an online questionnaire about their extracurricular experiences. Leadership development…

  19. Strategies for Effective Faculty Involvement in Online Activities Aimed at Promoting Critical Thinking and Deep Learning

    ERIC Educational Resources Information Center

    Abdul Razzak, Nina

    2016-01-01

    Highly-traditional education systems that mainly offer what is known as "direct instruction" usually result in graduates with a surface approach to learning rather than a deep one. What is meant by deep-learning is learning that involves critical analysis, the linking of ideas and concepts, creative problem solving, and application…

  20. Involving Children in Health and Social Research: "Human Becomings" or "Active Beings"?

    ERIC Educational Resources Information Center

    Balen, Rachel; Blyth, Eric; Calabretto, Helen; Fraser, Claire; Horrocks, Christine; Manby, Martin

    2006-01-01

    This article draws on the authors' experiences of undertaking health and social research involving children in Australia and England and focuses on securing the informed consent of children to participate in such research. A clear trend within literature, service provision, legislation and international conventions recognizes children as "active…

  1. Do a Little Dance: The Impact on Students when Librarians Get Involved in Extracurricular Activities

    ERIC Educational Resources Information Center

    Kasperek, Sheila; Johnson, Amber; Fotta, Katie; Craig, Francis

    2007-01-01

    One hundred fifty-two undergraduate students at Mansfield University of Pennsylvania were surveyed to determine if the involvement of their liaison librarian in theater productions and orchestra had an effect on their relationship with the library. The study shows positive and statistically significant results for students who participated in…

  2. Neural networks involved in adolescent reward processing: An activation likelihood estimation meta-analysis of functional neuroimaging studies.

    PubMed

    Silverman, Merav H; Jedd, Kelly; Luciana, Monica

    2015-11-15

    Behavioral responses to, and the neural processing of, rewards change dramatically during adolescence and may contribute to observed increases in risk-taking during this developmental period. Functional MRI (fMRI) studies suggest differences between adolescents and adults in neural activation during reward processing, but findings are contradictory, and effects have been found in non-predicted directions. The current study uses an activation likelihood estimation (ALE) approach for quantitative meta-analysis of functional neuroimaging studies to: (1) confirm the network of brain regions involved in adolescents' reward processing, (2) identify regions involved in specific stages (anticipation, outcome) and valence (positive, negative) of reward processing, and (3) identify differences in activation likelihood between adolescent and adult reward-related brain activation. Results reveal a subcortical network of brain regions involved in adolescent reward processing similar to that found in adults with major hubs including the ventral and dorsal striatum, insula, and posterior cingulate cortex (PCC). Contrast analyses find that adolescents exhibit greater likelihood of activation in the insula while processing anticipation relative to outcome and greater likelihood of activation in the putamen and amygdala during outcome relative to anticipation. While processing positive compared to negative valence, adolescents show increased likelihood for activation in the posterior cingulate cortex (PCC) and ventral striatum. Contrasting adolescent reward processing with the existing ALE of adult reward processing reveals increased likelihood for activation in limbic, frontolimbic, and striatal regions in adolescents compared with adults. Unlike adolescents, adults also activate executive control regions of the frontal and parietal lobes. These findings support hypothesized elevations in motivated activity during adolescence. PMID:26254587

  3. Prescribed Travel Schedules for Fatigue Management

    NASA Technical Reports Server (NTRS)

    Whitmire, Alexandra; Johnston, Smith; Lockley, Steven

    2011-01-01

    The NASA Fatigue Management Team is developing recommendations for managing fatigue during travel and for shift work operations, as Clinical Practice Guidelines for the Management of Circadian Desynchrony in ISS Operations. The Guidelines provide the International Space Station (ISS ) flight surgeons and other operational clinicians with evidence-based recommendations for mitigating fatigue and other factors related to sleep loss and circadian desynchronization. As much international travel is involved both before and after flight, the guidelines provide recommendations for: pre-flight training, in-flight operations, and post-flight rehabilitation. The objective of is to standardize the process by which care is provided to crewmembers, ground controllers, and other support personnel such as trainers, when overseas travel or schedule shifting is required. Proper scheduling of countermeasures - light, darkness, melatonin, diet, exercise, and medications - is the cornerstone for facilitating circadian adaptation, improving sleep, enhancing alertness, and optimizing performance. The Guidelines provide, among other things, prescribed travel schedules that outline the specific implementation of these mitigation strategies. Each travel schedule offers evidence based protocols for properly using the NASA identified countermeasures for fatigue. This presentation will describe the travel implementation schedules and how these can be used to alleviate the effects of jet lag and/or schedule shifts.

  4. 76 FR 11529 - Gregory Desobry, Ph.D.; Order Requiring Notification of Involvement in NRC-Licensed Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ... accordance with the NRC E-Filing rule (72 FR 49139, August 28, 2007). The E-Filing process requires... COMMISSION Gregory Desobry, Ph.D.; Order Requiring Notification of Involvement in NRC-Licensed Activities I... Mr. Desobry, Ph.D., requests a hearing, that person shall set forth with particularity the manner...

  5. Parental Involvement in School Activities and Reading Literacy: Findings and Implications from PIRLS 2011 Data. Policy Brief No. 3

    ERIC Educational Resources Information Center

    Mirazchiyski, Plamen; Klemencic, Eva

    2014-01-01

    This policy brief presents evidence demonstrating a positive association between parental involvement in school activities and student performance in the Progress in International Reading Literacy Study (PIRLS) 2011. This association, which was evident in most of the 54 education systems analyzed, indicates that students enrolled in schools with…

  6. 77 FR 39270 - In the Matter of Mr. Timothy Goold; Order Prohibiting Involvement in NRC-Licensed Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-02

    ... under 10 CFR 2.315(c), must be filed in accordance with the NRC E-Filing rule (72 FR 49139; August 28... COMMISSION In the Matter of Mr. Timothy Goold; Order Prohibiting Involvement in NRC-Licensed Activities I Mr... NRC in an attempt to resolve issues associated with this matter. Mr. Goold provided a written...

  7. 77 FR 31045 - Order Prohibiting Involvement in NRC-Licensed Activities; In the Matter of Jaime Sánchez

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ... under 10 CFR 2.315(c), must be filed in accordance with NRC E-Filing rule (72 FR 49139, August 28, 2007... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Order Prohibiting Involvement in NRC-Licensed Activities; In the Matter of Jaime S nchez I Jaime...

  8. 76 FR 11526 - In the Matter of Dr. Gary Kao; Order Prohibiting Involvement In NRC-Licensed Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ... entities participating under 10 CFR 2.315(c), must be filed in accordance with the NRC E-Filing rule (72 FR... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION In the Matter of Dr. Gary Kao; Order Prohibiting Involvement In NRC-Licensed Activities I Dr....

  9. 75 FR 55366 - In the Matter of Mark M. Ficek; Order Prohibiting Involvement in NRC-Licensed Activities...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-10

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION [Docket No. 030-20836, License No. 25-21479-01, NRC-2009-0120, A-10- 028] In the Matter of Mark M. Ficek; Order Prohibiting Involvement in NRC-Licensed Activities (Effective Immediately) Mr. Mark M. Ficek is the President, owner, and...

  10. 77 FR 49835 - Order Prohibiting Involvement in NRC-Licensed Activities; In the Matter of Mr. Joseph Quintanilla

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-17

    ... rule (72 FR 49139; August 28, 2007). The E-Filing process requires participants to submit and serve all... COMMISSION Order Prohibiting Involvement in NRC-Licensed Activities; In the Matter of Mr. Joseph Quintanilla.... Quintanilla indicated that he was aware the camera was outside of the dark room and did not contest...

  11. Cross-Age Tutorial Program To Increase Reading Comprehension through the Use of High Interest Activities Involving Reading.

    ERIC Educational Resources Information Center

    Leatherwood, Prudence Lee

    A practicum used a program of high interest activities involving reading to address the problem of low reading comprehension grades and test scores of eight students in the second through fourth grades, who were an average of 1 year behind the norm in reading. The program's six units included a listening unit, computer technology unit, daily…

  12. 41 CFR 51-7.2 - Early involvement in private, State, and local activities requiring Federal approval.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... involvement in private, State, and local activities requiring Federal approval. (a) 40 CFR 1501.2(d) requires... of 40 CFR 1501.2(d) with respect to these actions, the Committee staff shall consult as required with... requires an environmental assessment as set forth in 40 CFR 1501.4. (c) To facilitate compliance with...

  13. 41 CFR 51-7.2 - Early involvement in private, State, and local activities requiring Federal approval.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... involvement in private, State, and local activities requiring Federal approval. (a) 40 CFR 1501.2(d) requires... of 40 CFR 1501.2(d) with respect to these actions, the Committee staff shall consult as required with... requires an environmental assessment as set forth in 40 CFR 1501.4. (c) To facilitate compliance with...

  14. 41 CFR 51-7.2 - Early involvement in private, State, and local activities requiring Federal approval.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... involvement in private, State, and local activities requiring Federal approval. (a) 40 CFR 1501.2(d) requires... of 40 CFR 1501.2(d) with respect to these actions, the Committee staff shall consult as required with... requires an environmental assessment as set forth in 40 CFR 1501.4. (c) To facilitate compliance with...

  15. Expectations of Rock Music Consumption for Entertainment and Information Relative to the Active Involvement of the User.

    ERIC Educational Resources Information Center

    Rouner, Donna; Noyes, Amy

    Before examining potentially negative effects of rock music on adolescents, it is necessary to demonstrate links between adolescent motivations for consuming rock music and active involvement relative to that use and also to consider how much rock listeners rely on rock music as a source for information about values, beliefs, and social…

  16. 41 CFR 51-7.2 - Early involvement in private, State, and local activities requiring Federal approval.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... involvement in private, State, and local activities requiring Federal approval. (a) 40 CFR 1501.2(d) requires... of 40 CFR 1501.2(d) with respect to these actions, the Committee staff shall consult as required with... requires an environmental assessment as set forth in 40 CFR 1501.4. (c) To facilitate compliance with...

  17. 41 CFR 51-7.2 - Early involvement in private, State, and local activities requiring Federal approval.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... involvement in private, State, and local activities requiring Federal approval. (a) 40 CFR 1501.2(d) requires... of 40 CFR 1501.2(d) with respect to these actions, the Committee staff shall consult as required with... requires an environmental assessment as set forth in 40 CFR 1501.4. (c) To facilitate compliance with...

  18. Predicting Adolescents' Organized Activity Involvement: The Role of Maternal Depression History, Family Relationship Quality, and Adolescent Cognitions

    ERIC Educational Resources Information Center

    Bohnert, Amy M.; Martin, Nina C.; Garber, Judy

    2007-01-01

    Although the potential benefits of organized activity involvement during high school have been documented, little is known about what familial and individual characteristics are associated with higher levels of participation. Using structural equation modeling, this longitudinal study examined the extent to which maternal depression history (i.e.,…

  19. Children's Well-Being and Involvement in Physically Active Outdoors Play in a Norwegian Kindergarten: Playful Sharing of Physical Experiences

    ERIC Educational Resources Information Center

    Bjørgen, Kathrine

    2015-01-01

    This qualitative study explores the conditions of children's level of well-being and their involvement in physically active play during kindergarten outdoors time. Observations of three to five year olds from one kindergarten in central Norway were conducted. The researcher followed the children around the kindergarten's outdoors playground and…

  20. Melanosis in Penaeus monodon: Involvement of the Laccase-like Activity of Hemocyanin.

    PubMed

    Bris, Cédric Le; Cudennec, Benoit; Dhulster, Pascal; Drider, Djamel; Duflos, Guillaume; Grard, Thierry

    2016-01-27

    In shrimp, the development of postmortem melanosis resulting from phenoloxidase activities leads to important economic losses. Phenoloxidase enzymes include catechol oxidases, laccases, and tyrosinases, but hemocyanin is also capable of phenoloxidase activities. These activities have been explored in Penaeus monodon, using different substrates. Results highlighted that tyrosinase-specific substrates were little oxidized, whereas hydroquinone (laccase-specific substrate) was more highly oxidized than l-DOPA (nonspecific substrate) in the pereopods and pleopods. Global phenoloxidase activity, assayed with l-DOPA, did not appear thermally stable over time and probably resulted from phenoloxidase enzymes. Conversely, the laccase-like activity assayed with hydroquinone was thermally stable over time, reflecting the thermal stability of hemocyanin. Independently of the anatomical compartment, the temperature, or the substrate, the highest activities were assayed in the cuticular compartments. This study demonstrates the complexity of phenoloxidase activities in P. monodon, and the importance of considering all the activities, including laccase-like activities such as that of hemocyanin. PMID:26671070

  1. Activity-Dependent Dendritic Spine Shrinkage and Growth Involve Downregulation of Cofilin via Distinct Mechanisms

    PubMed Central

    Calabrese, Barbara; Saffin, Jean-Michel; Halpain, Shelley

    2014-01-01

    A current model posits that cofilin-dependent actin severing negatively impacts dendritic spine volume. Studies suggested that increased cofilin activity underlies activity-dependent spine shrinkage, and that reduced cofilin activity induces activity-dependent spine growth. We suggest instead that both types of structural plasticity correlate with decreased cofilin activity. However, the mechanism of inhibition determines the outcome for spine morphology. RNAi in rat hippocampal cultures demonstrates that cofilin is essential for normal spine maintenance. Cofilin-F-actin binding and filament barbed-end production decrease during the early phase of activity-dependent spine shrinkage; cofilin concentration also decreases. Inhibition of the cathepsin B/L family of proteases prevents both cofilin loss and spine shrinkage. Conversely, during activity-dependent spine growth, LIM kinase stimulates cofilin phosphorylation, which activates phospholipase D-1 to promote actin polymerization. These results implicate novel molecular mechanisms and prompt a revision of the current model for how cofilin functions in activity-dependent structural plasticity. PMID:24740405

  2. A format for the interchange of scheduling models

    NASA Technical Reports Server (NTRS)

    Jaap, John P.; Davis, Elizabeth K.

    1994-01-01

    In recent years a variety of space-activity schedulers have been developed within the aerospace community. Space-activity schedulers are characterized by their need to handle large numbers of activities which are time-window constrained and make high demands on many scarce resources, but are minimally constrained by predecessor/successor requirements or critical paths. Two needs to exchange data between these schedulers have materialized. First, there is significant interest in comparing and evaluating the different scheduling engines to ensure that the best technology is applied to each scheduling endeavor. Second, there is a developing requirement to divide a single scheduling task among different sites, each using a different scheduler. In fact, the scheduling task for International Space Station Alpha (ISSA) will be distributed among NASA centers and among the international partners. The format used to interchange scheduling data for ISSA will likely use a growth version of the format discussed in this paper. The model interchange format (or MIF, pronounced as one syllable) discussed in this paper is a robust solution to the need to interchange scheduling requirements for space activities. It is highly extensible, human-readable, and can be generated or edited with common text editors. It also serves well the need to support a 'benchmark' data case which can be delivered on any computer platform.

  3. INVOLVEMENT OF PEPTIDOGLYCAN RECOGNITION PROTEIN L6 IN ACTIVATION OF IMMUNE DEFICIENCY PATHWAY IN THE IMMUNE RESPONSIVE SILKWORM CELLS.

    PubMed

    Tanaka, Hiromitsu; Sagisaka, Aki

    2016-06-01

    The immune deficiency (Imd) signaling pathway is activated by Gram-negative bacteria for producing antimicrobial peptides (AMPs). In Drosophila melanogaster, the activation of this pathway is initiated by the recognition of Gram-negative bacteria by peptidoglycan (PGN) recognition proteins (PGRPs), PGRP-LC and PGRP-LE. In this study, we found that the Imd pathway is involved in enhancing the promoter activity of AMP gene in response to Gram-negative bacteria or diaminopimelic (DAP) type PGNs derived from Gram-negative bacteria in an immune responsive silkworm cell line, Bm-NIAS-aff3. Using gene knockdown experiments, we further demonstrated that silkworm PGRP L6 (BmPGRP-L6) is involved in the activation of E. coli or E. coli-PGN mediated AMP promoter activation. Domain analysis revealed that BmPGRP-L6 contained a conserved PGRP domain, transmembrane domain, and RIP homotypic interaction motif like motif but lacked signal peptide sequences. BmPGRP-L6 overexpression enhances AMP promoter activity through the Imd pathway. BmPGRP-L6 binds to DAP-type PGNs, although it also binds to lysine-type PGNs that activate another immune signal pathway, the Toll pathway in Drosophila. These results indicate that BmPGRP-L6 is a key PGRP for activating the Imd pathway in immune responsive silkworm cells. PMID:26991439

  4. A qualitative study of the activities performed by people involved in clinical decision support: recommended practices for success

    PubMed Central

    Wright, Adam; Ash, Joan S; Erickson, Jessica L; Wasserman, Joe; Bunce, Arwen; Stanescu, Ana; St Hilaire, Daniel; Panzenhagen, Morgan; Gebhardt, Eric; McMullen, Carmit; Middleton, Blackford; Sittig, Dean F

    2014-01-01

    Objective To describe the activities performed by people involved in clinical decision support (CDS) at leading sites. Materials and methods We conducted ethnographic observations at seven diverse sites with a history of excellence in CDS using the Rapid Assessment Process and analyzed the data using a series of card sorts, informed by Linstone's Multiple Perspectives Model. Results We identified 18 activities and grouped them into four areas. Area 1: Fostering relationships across the organization, with activities (a) training and support, (b) visibility/presence on the floor, (c) liaising between people, (d) administration and leadership, (e) project management, (f) cheerleading/buy-in/sponsorship, (g) preparing for CDS implementation. Area 2: Assembling the system with activities (a) providing technical support, (b) CDS content development, (c) purchasing products from vendors (d) knowledge management, (e) system integration. Area 3: Using CDS to achieve the organization's goals with activities (a) reporting, (b) requirements-gathering/specifications, (c) monitoring CDS, (d) linking CDS to goals, (e) managing data. Area 4: Participation in external policy and standards activities (this area consists of only a single activity). We also identified a set of recommendations associated with these 18 activities. Discussion All 18 activities we identified were performed at all sites, although the way they were organized into roles differed substantially. We consider these activities critical to the success of a CDS program. Conclusions A series of activities are performed by sites strong in CDS, and sites adopting CDS should ensure they incorporate these activities into their efforts. PMID:23999670

  5. An analysis of the impact of three high school schedules on student achievement in advanced placement biology classes

    NASA Astrophysics Data System (ADS)

    Arons-Polan, Bonnie

    This study examined the effect of three schedule types on student achievement in Advanced Placement Biology classes. AP Biology test scores from students on three types of full-year schedules were analyzed to assess the impact schedule type had on student achievement. The three schedules included the block and traditional schedules, and the rotating/hybrid, a blend of the former two schedules. The results indicated the variable most closely associated with success on the AP Biology exam was the length of experience the teachers had teaching the course, regardless of schedule type. Although significant differences were seen in mean AP Biology test scores among the three schedule types, this could be explained by the relationship between instructors' experience and schedule type. Regression analysis determined the two strongest predictors of successful performance on the AP Biology exam were instructors' experience and perceived teaching style, regardless of schedule type. It appears that the economically developed suburbs, had teachers with the largest amount of experience teaching AP Biology, and these teachers reported using a direct approach to teaching, using lecture greater than 50% of the time. The results of this study also suggest when restructuring to improve student achievement, educators should examine other variables in addition to the high school schedule. Restructuring the day to allow for longer classes must be accompanied by professional staff development to allow teachers to develop new teaching methods. Most of the teachers in the survey reported using lecture a great deal of the time, regardless of schedule type. Comments from the teachers from the various schedules revealed that the ability to add student centered, inquiry based activities and labs were dependent on adequate class time. No information on whether or not the teachers were given professional development to expand their repertoire of teaching methods when the school adopted a block

  6. PLAN-IT: Scheduling assistant for solar system exploration

    NASA Technical Reports Server (NTRS)

    Dias, William C.; Henricks, Julia A.; Wong, Jennifer C.

    1987-01-01

    A frame-based expert scheduling system shell, PLAN-IT, is developed for spacecraft scheduling in the Request Integration Phase, using the Comet Rendezvous Asteroid Flyby (CRAF) mission as a development base. Basic, structured, and expert scheduling techniques are reviewed. Data elements such as activity representation and resource conflict representation are discussed. Resource constraints include minimum and maximum separation times between activities, percentage of time pointed at specific targets, and separation time between targeted intervals of a given activity. The different scheduling technique categories and the rationale for their selection are also considered.

  7. PLAN-IT - Scheduling assistant for solar system exploration

    NASA Technical Reports Server (NTRS)

    Dias, William C.; Henricks, Julia A.; Wong, Jennifer C.

    1987-01-01

    A frame-based expert scheduling system shell, PLAN-IT, is developed for spacecraft scheduling in the Request Integration Phase, using the Comet Rendezvous Asteroid Flyby (CRAF) mission as a development base. Basic, structured, and expert scheduling techniques are reviewed. Data elements such as activity representation and resource conflict representation are discussed. Resource constraints include minimum and maximum separation times between activities, percentage of time pointed at specific targets, and separation time between targeted intervals of a given activity. The different scheduling technique categories and the rationale for their selection are also considered.

  8. Family and Community Involvement in the Comprehensive School Physical Activity Program

    ERIC Educational Resources Information Center

    Cipriani, Kristin; Richardson, Cheryl; Roberts, Georgi

    2012-01-01

    Engaging families and communities in physical activities for the benefit of children is an extension of the role of a physical education instructor. Although it is possible for a physical educator to generate ideas that encourage families and communities to move, a certified director of physical activity (C-DPA) would be better trained to…

  9. Discovering the Thermodynamics of Simultaneous Equilibria: An Entropy Analysis Activity Involving Consecutive Equilibria

    ERIC Educational Resources Information Center

    Bindel, Thomas H.

    2007-01-01

    An activity is presented in which the thermodynamics of simultaneous, consecutive equilibria are explored. The activity is appropriate for second-year high school or AP chemistry. Students discover that a reactant-favored (entropy-diminishing or endergonic) reaction can be caused to happen if it is coupled with a product-favored reaction of…

  10. Optical Topography of Evoked Brain Activity during Mental Tasks Involving Whole Number Operations

    ERIC Educational Resources Information Center

    Ortiz, Enrique

    2014-01-01

    Students start to memorize arithmetic facts from early elementary school mathematics activities. Their fluency or lack of fluency with these facts could affect their efforts as they carry out mental calculations as adults. This study investigated participants' levels of brain activation and possible reasons for these levels as they solved…

  11. Mutational analysis of the major soybean UreF paralogue involved in urease activation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In soybean, mutation at Eu2 or Eu3 eliminates the urease activities of both the embryo-specific and the tissue-ubiquitous (assimilatory) isozymes, encoded by Eu1 and Eu4, respectively. Eu3 encodes UreG, a GTP’ase necessary for proper emplacement of Ni and carbon dioxide in the urease active site. ...

  12. Involvement of Cot activity in the proliferation of ALCL lymphoma cells

    SciTech Connect

    Fernandez, Margarita; Manso, Rebeca; Bernaldez, Flavia; Lopez, Pilar; Martin-Duce, Antonio; Alemany, Susana

    2011-08-12

    Highlights: {yields} We show here that ALCL lymphoma cell lines present high levels of Cot (MAP3K8). {yields} We show that Cot mediates the constitutive Erk1/2 activation in SUDHL-1 cells. {yields} Inhibition of Cot activity reduces the number of cell divisions in SUDHL-1 cells. {yields} Cot controls the activation state of p70 S6K and JunB expression in SUDHL-1 cells. -- Abstract: Anaplastic large-cell lymphoma (ALCL) cells overexpress CD30 on their cell surface, show increased levels of activated Erk1/2 and of JunB; participating JunB in the proliferative capacity of these lymphomas. Here, we show that ALCL lymphoma cells also present high expression levels of the proto-oncogenic Cot (MAP3K8). Using pharmacological drugs as well as the RNA interference technique we show that Cot protein is responsible for the constitutive Erk1/2 activation in the ALCL lymphoma cells, SUDHL-1. Besides, inhibition of Cot activity reduces the number of cell divisions which is achieved, at least in part, by the control that Cot exercises on the activation state of p70 S6K and on the expression levels of JunB. Since Cot represents an alternative mode, independently of RAF, to activate Erk1/2, all these data strongly suggest that molecular targeting of Cot may be a potential new specific strategy for ALCL lymphomas therapy, without the fully disturbance of the Erk1/2 function.

  13. Community College Involvement in Contract Training and Other Economic Development Activities.

    ERIC Educational Resources Information Center

    Lynch, Robert; And Others

    In 1989-90, a national survey was conducted to assess the scope and nature of contract training and other economic development activities at community colleges and technical institutes. The survey was sent to a random sample of 246 community colleges, requesting information on the colleges' workforce and economic development activities in 1988-89.…

  14. Control of 5-aminolaevulinate synthetase activity in Rhodopseudomonas spheroides. The involvement of sulphur metabolism

    PubMed Central

    Neuberger, Albert; Sandy, John D.; Tait, George H.

    1973-01-01

    1. The `initial' 5-aminolaevulinate synthetase activity, that is the activity observed immediately after cell disruption, in extracts prepared from unharvested semianaerobically grown Rhodopseudomonas spheroides, was twice that observed under the same assay conditions in extracts prepared from harvested cells. 2. The effect of oxygenation of a culture on the `maximum' aminolaevulinate synthetase activity, that is the activity observed 1h after disruption of harvested cells, is markedly influenced by the contents of the growth medium. Oxygenation of organisms for 1h in the medium in which they have grown produces an 80–90% decrease in maximum activity, whereas similar treatment of organisms resuspended in fresh medium produces less than a 40% decrease. 3. This protective effect of fresh medium is absolutely dependent on the presence of sulphate. When cells are suspended in sulphate-deficient fresh medium, the maximum activity falls by 65–75% even without oxygenation. A high maximum activity is regenerated when sulphate is resupplied. 4. When organisms are oxygenated in the medium in which they have grown, the cellular contents of GSH+GSSG and cysteine+cystine fall very markedly and homolanthionine is formed. Both the fall in aminolaevulinate synthetase activity and the changes in sulphur metabolism are largely prevented by the addition of compounds which stimulate synthesis of cysteine de novo or inhibit the conversion of cysteine S into homocysteine S. 5. The maximum aminolaevulinate synthetase activity was directly proportional to the GSH+GSSG content of all cell preparations. In glutathione-depleted extracts the `low'-activity enzyme could be re-activated in vitro by the addition of GSH, GSSG, cysteine or cystine, whereas in extracts with a high glutathione content the `high'-activity enzyme was unaffected by these sulphur compounds. 6. The activation of low-activity enzyme with exogenous sulphur compounds was prevented by excluding air or by adding NADH

  15. SPANR planning and scheduling

    NASA Astrophysics Data System (ADS)

    Freund, Richard F.; Braun, Tracy D.; Kussow, Matthew; Godfrey, Michael; Koyama, Terry

    2001-07-01

    SPANR (Schedule, Plan, Assess Networked Resources) is (i) a pre-run, off-line planning and (ii) a runtime, just-in-time scheduling mechanism. It is designed to support primarily commercial applications in that it optimizes throughput rather than individual jobs (unless they have highest priority). Thus it is a tool for a commercial production manager to maximize total work. First the SPANR Planner is presented showing the ability to do predictive 'what-if' planning. It can answer such questions as, (i) what is the overall effect of acquiring new hardware or (ii) what would be the effect of a different scheduler. The ability of the SPANR Planner to formulate in advance tree-trimming strategies is useful in several commercial applications, such as electronic design or pharmaceutical simulations. The SPANR Planner is demonstrated using a variety of benchmarks. The SPANR Runtime Scheduler (RS) is briefly presented. The SPANR RS can provide benefit for several commercial applications, such as airframe design and financial applications. Finally a design is shown whereby SPANR can provide scheduling advice to most resource management systems.

  16. Baking together-the coordination of actions in activities involving people with dementia.

    PubMed

    Majlesi, Ali Reza; Ekström, Anna

    2016-08-01

    This study explores interaction and collaboration between people with dementia and their spouses in relation to the performance of household chores with the focus on instruction as an interactional context to engage the person with dementia in collaboration to accomplish joint activities. Dementia is generally associated with pathological changes in people's cognitive functions such as diminishing memory functions, communicative abilities and also diminishing abilities to take initiative as well as to plan and execute tasks. Using video recordings of everyday naturally occurring activities, we analyze the sequential organization of actions (see Schegloff, 2007) oriented toward the accomplishment of a joint multi-task activity of baking. The analysis shows the specific ways of collaboration through instructional activities in which the person with dementia exhibits his competence and skills in accomplishing the given tasks through negotiating the instructions with his partner and carrying out instructed actions. Although the driving force of the collaboration seems to be a series of directive sequences only initiated by the partner throughout the baking activity, our analyses highlight how the person with dementia can actively use the material environment-including collaborating partners-to compensate for challenges and difficulties encountered in achieving everyday tasks. The sequential organization of instructions and instructed actions are in this sense argued to provide an interactional environment wherein the person with dementia can make contributions to the joint activity in an efficient way. While a collaborator has been described as necessary for a person with dementia to be able to partake in activities, this study shows that people with dementia are not only guided by their collaborators in joint activities but they can also actively use their collaborators in intricate compensatory ways. PMID:27531451

  17. Scheduling for Public Service in International Operations

    NASA Technical Reports Server (NTRS)

    Brenner, M. A.

    1972-01-01

    The factors involved in scheduling airline services for international operations are discussed. Charts are presented to show the transatlantic pattern of flights for a typical airline during the summer and winter months. The operations of a domestic airline operating overseas and a foreign airline operating to the United States are compared.

  18. 40 CFR 52.730 - Compliance schedules.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., 1973. lake county Morton Manufacturing Co Libertyville 205(f) Aug. 27, 1973. la salle county Allied... Regulation involved Date schedule adopted christian county Allied Mills, Inc Taylorville 204(c) Feb. 28, 1973. cook county Harco Aluminum Inc Chicago 204(c) Dec. 9, 1973. J. L. Clark Manufacturing Co Downers...

  19. 40 CFR 52.730 - Compliance schedules.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., 1973. lake county Morton Manufacturing Co Libertyville 205(f) Aug. 27, 1973. la salle county Allied... Regulation involved Date schedule adopted christian county Allied Mills, Inc Taylorville 204(c) Feb. 28, 1973. cook county Harco Aluminum Inc Chicago 204(c) Dec. 9, 1973. J. L. Clark Manufacturing Co Downers...

  20. 40 CFR 52.730 - Compliance schedules.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., 1973. lake county Morton Manufacturing Co Libertyville 205(f) Aug. 27, 1973. la salle county Allied... Regulation involved Date schedule adopted christian county Allied Mills, Inc Taylorville 204(c) Feb. 28, 1973. cook county Harco Aluminum Inc Chicago 204(c) Dec. 9, 1973. J. L. Clark Manufacturing Co Downers...

  1. 40 CFR 52.730 - Compliance schedules.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., 1973. lake county Morton Manufacturing Co Libertyville 205(f) Aug. 27, 1973. la salle county Allied... Regulation involved Date schedule adopted christian county Allied Mills, Inc Taylorville 204(c) Feb. 28, 1973. cook county Harco Aluminum Inc Chicago 204(c) Dec. 9, 1973. J. L. Clark Manufacturing Co Downers...

  2. 40 CFR 52.730 - Compliance schedules.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., 1973. lake county Morton Manufacturing Co Libertyville 205(f) Aug. 27, 1973. la salle county Allied... Regulation involved Date schedule adopted christian county Allied Mills, Inc Taylorville 204(c) Feb. 28, 1973. cook county Harco Aluminum Inc Chicago 204(c) Dec. 9, 1973. J. L. Clark Manufacturing Co Downers...

  3. 40 CFR 52.825 - Compliance schedules.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... schedule. Editorial Note: For Federal Register citations affecting § 52.825, see the List of CFR Sections... analysis and results. (2) Where any such owner or operator demonstrates to the satisfaction of the.... Iowa Source Location Regulation involved Date adopted Variance expiration date Final compliance...

  4. 40 CFR 52.825 - Compliance schedules.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... schedule. Editorial Note: For Federal Register citations affecting § 52.825, see the List of CFR Sections... analysis and results. (2) Where any such owner or operator demonstrates to the satisfaction of the.... Iowa Source Location Regulation involved Date adopted Variance expiration date Final compliance...

  5. 40 CFR 52.825 - Compliance schedules.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... schedule. Editorial Note: For Federal Register citations affecting § 52.825, see the List of CFR Sections... analysis and results. (2) Where any such owner or operator demonstrates to the satisfaction of the.... Iowa Source Location Regulation involved Date adopted Variance expiration date Final compliance...

  6. 40 CFR 52.825 - Compliance schedules.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... schedule. Editorial Note: For Federal Register citations affecting § 52.825, see the List of CFR Sections... analysis and results. (2) Where any such owner or operator demonstrates to the satisfaction of the.... Iowa Source Location Regulation involved Date adopted Variance expiration date Final compliance...

  7. Schedule-Tracker Computer Program

    NASA Technical Reports Server (NTRS)

    Collazo, Fernando F.

    1990-01-01

    Schedule Tracker provides effective method for tracking tasks "past due" and/or "near term". Generates reports for each responsible staff member having one or more assigned tasks falling within two listed categories. Schedule Organizer (SO) (COSMIC program MSC-21525), Schedule Tracker (ST), and Schedule Report Generator (SRG) (COSMIC program MSC-21527) computer programs manipulating data-base files in ways advantageous in scheduling. Written in PL/1 and DEC Command Language (DCL).

  8. Automated Scheduling Via Artificial Intelligence

    NASA Technical Reports Server (NTRS)

    Biefeld, Eric W.; Cooper, Lynne P.

    1991-01-01

    Artificial-intelligence software that automates scheduling developed in Operations Mission Planner (OMP) research project. Software used in both generation of new schedules and modification of existing schedules in view of changes in tasks and/or available resources. Approach based on iterative refinement. Although project focused upon scheduling of operations of scientific instruments and other equipment aboard spacecraft, also applicable to such terrestrial problems as scheduling production in factory.

  9. Involvement of antioxidant activity of Lactobacillus plantarum on functional properties of olive phenolic compounds.

    PubMed

    Kachouri, Faten; Ksontini, Hamida; Kraiem, Manel; Setti, Khaoula; Mechmeche, Manel; Hamdi, Moktar

    2015-12-01

    Eight lactic acid bacteria strains isolated from traditional fermented foods were investigated for their antioxidant activity against DPPH free radicals, β-carotene bleaching assay and linoleic acid test. L. plantarum LAB 1 at a dose of 8.2 10(9) CFU/ml showed the highest DPPH scavenging activity, with inhibition rate of 57.07 ± 0.57 % and an antioxidant activity (TAA = 43.47 ± 0.663 % and AAC = 172.65 ± 5.57), which increase with cell concentrations. When L. plantarum LAB 1 was administered to oxidative enzymes, residual activities decreased significantly with cell concentrations. The use of L. plantarum LAB 1 on olives process, favours the increase of the antioxidant activity (24 %). HPLC results showed a significant increase of orthodiphenols (74 %). Viable cells of strain were implicated directly on minimum media growth with 500 mg/l of olive phenolic compounds. Results showed an increase in their antioxidant activity. CG-SM analysis, identify the presence of compounds with higher antioxidant activity as vinyl phenol and hydroxytyrosol. PMID:26604364

  10. [Physiology of protease-activated receptors (PARs): involvement of PARs in digestive functions].

    PubMed

    Kawabata, A; Kuroda, R; Hollenberg, M D

    1999-10-01

    The protease-activated receptor (PAR), a G protein-coupled receptor present on cell surface, mediates cellular actions of extracellular proteases. Proteases cleave the extracellular N-terminal of PAR molecules at a specific site, unmasking and exposing a novel N-terminal, a tethered ligand, that binds to the body of receptor molecules resulting in receptor activation. Amongst four distinct PARs that have been cloned, PARs 1, 3 and 4 are activated by thrombin, but PAR-2 is activated by trypsin or mast cell tryptase. Human platelets express two distinct thrombin receptors, PAR-1 and PAR-4, while murine platelets express PAR-3 and PAR-4. Apart from roles of PARs in platelet activation, PARs are distributed to a number of organs in various species, predicting their physiological importance. We have been evaluating agonists specific for each PAR, using multiple procedures including a HEK cell calcium signal receptor desensitization assay. Using specific agonists that we developed, we found the following: 1) the salivary glands express PAR-2 mRNA and secret saliva in response to PAR-2 activation; 2) pancreatic juice secretion occurs following in vivo PAR-2 activation; 3) PAR-1 and PAR-2 modulate duodenal motility. Collectively, PAR plays various physiological and/or pathophysiological roles, especially in the digestive systems, and could be a novel target for drug development. PMID:10629876

  11. The application of connectionism to query planning/scheduling in intelligent user interfaces

    NASA Technical Reports Server (NTRS)

    Short, Nicholas, Jr.; Shastri, Lokendra

    1990-01-01

    In the mid nineties, the Earth Observing System (EOS) will generate an estimated 10 terabytes of data per day. This enormous amount of data will require the use of sophisticated technologies from real time distributed Artificial Intelligence (AI) and data management. Without regard to the overall problems in distributed AI, efficient models were developed for doing query planning and/or scheduling in intelligent user interfaces that reside in a network environment. Before intelligent query/planning can be done, a model for real time AI planning and/or scheduling must be developed. As Connectionist Models (CM) have shown promise in increasing run times, a connectionist approach to AI planning and/or scheduling is proposed. The solution involves merging a CM rule based system to a general spreading activation model for the generation and selection of plans. The system was implemented in the Rochester Connectionist Simulator and runs on a Sun 3/260.

  12. Considerations for Using an Incremental Scheduler for Human Exploration Task Scheduling

    NASA Technical Reports Server (NTRS)

    Jaap, John; Phillips, Shaun

    2005-01-01

    As humankind embarks on longer space missions farther from home, the requirements and environments for scheduling the activities performed on these missions are changing. As we begin to prepare for these missions it is appropriate to evaluate the merits and applicability of the different types of scheduling engines. Scheduling engines temporally arrange tasks onto a timeline so that all constraints and objectives are met and resources are not overbooked. Scheduling engines used to schedule space missions fall into three general categories: batch, mixed-initiative, and incremental. This paper presents an assessment of the engine types, a discussion of the impact of human exploration of the moon and Mars on planning and scheduling, and the applicability of the different types of scheduling engines. This paper will pursue the hypothesis that incremental scheduling engines may have a place in the new environment; they have the potential to reduce cost, to improve the satisfaction of those who execute or benefit from a particular timeline (the customers), and to allow astronauts to plan their own tasks.

  13. B cell activation involves nanoscale receptor reorganizations and inside-out signaling by Syk

    PubMed Central

    Kläsener, Kathrin; Maity, Palash C; Hobeika, Elias; Yang, Jianying; Reth, Michael

    2014-01-01

    Binding of antigen to the B cell antigen receptor (BCR) initiates a multitude of events resulting in B cell activation. How the BCR becomes signaling-competent upon antigen binding is still a matter of controversy. Using a high-resolution proximity ligation assay (PLA) to monitor the conformation of the BCR and its interactions with co-receptors at a 10–20 nm resolution, we provide direct evidence for the opening of BCR dimers during B cell activation. We also show that upon binding Syk opens the receptor by an inside-out signaling mechanism that amplifies BCR signaling. Furthermore, we found that on resting B cells, the coreceptor CD19 is in close proximity with the IgD-BCR and on activated B cells with the IgM-BCR, indicating nanoscale reorganization of receptor clusters during B cell activation. DOI: http://dx.doi.org/10.7554/eLife.02069.001 PMID:24963139

  14. Directory of DOE and contractor personnel involved in non-government standards activities

    SciTech Connect

    1995-08-01

    This document contains a listing of DOE employees and DOE contractors who have submitted form DOE F 1300.2, Record of Non-Government Standards Activity. Additional names were added from rosters supplied by non-Government standards bodies.

  15. Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway

    SciTech Connect

    Nagane, Masaki; Yasui, Hironobu; Sakai, Yuri; Yamamori, Tohru; Niwa, Koichi; Hattori, Yuichi; Kondo, Takashi; Inanami, Osamu

    2015-01-02

    Highlights: • eNOS activity is increased in BAECs exposed to X-rays. • ATM is involved in this increased eNOS activity. • HSP90 modulates the radiation-induced activation of ATM and eNOS. - Abstract: In this study, the involvement of ataxia telangiectasia mutated (ATM) kinase and heat shock protein 90 (HSP90) in endothelial nitric oxide synthase (eNOS) activation was investigated in X-irradiated bovine aortic endothelial cells. The activity of nitric oxide synthase (NOS) and the phosphorylation of serine 1179 of eNOS (eNOS-Ser1179) were significantly increased in irradiated cells. The radiation-induced increases in NOS activity and eNOS-Ser1179 phosphorylation levels were significantly reduced by treatment with either an ATM inhibitor (Ku-60019) or an HSP90 inhibitor (geldanamycin). Geldanamycin was furthermore found to suppress the radiation-induced phosphorylation of ATM-Ser1181. Our results indicate that the radiation-induced eNOS activation in bovine aortic endothelial cells is regulated by ATM and HSP90.

  16. Involvement of Antibiotic Efflux Machinery in Glutathione-Mediated Decreased Ciprofloxacin Activity in Escherichia coli.

    PubMed

    Goswami, Manish; Subramanian, Mahesh; Kumar, Ranjeet; Jass, Jana; Jawali, Narendra

    2016-07-01

    We have analyzed the contribution of different efflux components to glutathione-mediated abrogation of ciprofloxacin's activity in Escherichia coli and the underlying potential mechanism(s) behind this phenomenon. The results indicated that glutathione increased the total active efflux, thereby partially contributing to glutathione-mediated neutralization of ciprofloxacin's antibacterial action in E. coli However, the role of glutathione-mediated increased efflux becomes evident in the absence of a functional TolC-AcrAB efflux pump. PMID:27139480

  17. Cdc42-Dependent Activation of NADPH Oxidase Is Involved in Ethanol-Induced Neuronal Oxidative Stress

    PubMed Central

    Wang, Xin; Ke, Zunji; Chen, Gang; Xu, Mei; Bower, Kimberly A.; Frank, Jacqueline A.; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2012-01-01

    It has been suggested that excessive reactive oxygen species (ROS) and oxidative stress play an important role in ethanol-induced damage to both the developing and mature central nervous system (CNS). The mechanisms underlying ethanol-induced neuronal ROS, however, remain unclear. In this study, we investigated the role of NADPH oxidase (NOX) in ethanol-induced ROS generation. We demonstrated that ethanol activated NOX and inhibition of NOX reduced ethanol-promoted ROS generation. Ethanol significantly increased the expression of p47phox and p67phox, the essential subunits for NOX activation in cultured neuronal cells and the cerebral cortex of infant mice. Ethanol caused serine phosphorylation and membrane translocation of p47phox and p67phox, which were prerequisites for NOX assembly and activation. Knocking down p47phox with the small interfering RNA was sufficient to attenuate ethanol-induced ROS production and ameliorate ethanol-mediated oxidative damage, which is indicated by a decrease in protein oxidation and lipid peroxidation. Ethanol activated cell division cycle 42 (Cdc42) and overexpression of a dominant negative (DN) Cdc42 abrogate ethanol-induced NOX activation and ROS generation. These results suggest that Cdc42-dependent NOX activation mediates ethanol-induced oxidative damages to neurons. PMID:22662267

  18. Stretch-induced uterine myocyte differentiation during rat pregnancy: involvement of caspase activation.

    PubMed

    Shynlova, Oksana; Dorogin, Anna; Lye, Stephen J

    2010-06-01

    Proliferation, differentiation, and apoptosis are three major processes by which the pregnant uterus maintains homeostasis to accommodate the growing fetus. We demonstrated previously that caspase activation in the pregnant rat myometrium at midgestation coincides with the transition from uterine hyperplasia to hypertrophy. We hypothesized that this transition was induced by stasis of myometrial blood flow (and subsequent hypoxia/ischaemia insult) resulting from acute myometrial stretch induced by a growing embryo. Therefore, we measured the expression of active caspase 3 and two hypoxia markers (transcription factor HIF1A and pimonidazole hydrochloride) in pregnant rat myometrium. To investigate the effect of gravidity we used unilaterally pregnant rats. Caspase 3 was activated only in the gravid horn of the unilaterally pregnant animals on Gestational Days 12-15. This activation was associated with high levels of HIF1A and pimonidazole immunostaining, which were limited to the circular myometrial layer of the gravid horn, indicative of hypoxia within this tissue. To isolate the effect of myometrial stretch applied by the growing fetus, we inserted an expandable polymer tube (intra-uterine expandable tube [IUET]) into the empty horn of Day 13 and Day 20 unilaterally pregnant rats. Tissue was collected 2, 14, and 24 h later. In the IUET-stretched empty horn, cleaved caspase 3 was activated at midgestation (Day 14), but not at late gestation (Day 21). We speculate that hypoxia resulting from mechanical stretch may activate caspase 3 within the pregnant myometrium only in the context of a specific endocrine environment. PMID:20181619

  19. Scheduling with genetic algorithms

    NASA Technical Reports Server (NTRS)

    Fennel, Theron R.; Underbrink, A. J., Jr.; Williams, George P. W., Jr.

    1994-01-01

    In many domains, scheduling a sequence of jobs is an important function contributing to the overall efficiency of the operation. At Boeing, we develop schedules for many different domains, including assembly of military and commercial aircraft, weapons systems, and space vehicles. Boeing is under contract to develop scheduling systems for the Space Station Payload Planning System (PPS) and Payload Operations and Integration Center (POIC). These applications require that we respect certain sequencing restrictions among the jobs to be scheduled while at the same time assigning resources to the jobs. We call this general problem scheduling and resource allocation. Genetic algorithms (GA's) offer a search method that uses a population of solutions and benefits from intrinsic parallelism to search the problem space rapidly, producing near-optimal solutions. Good intermediate solutions are probabalistically recombined to produce better offspring (based upon some application specific measure of solution fitness, e.g., minimum flowtime, or schedule completeness). Also, at any point in the search, any intermediate solution can be accepted as a final solution; allowing the search to proceed longer usually produces a better solution while terminating the search at virtually any time may yield an acceptable solution. Many processes are constrained by restrictions of sequence among the individual jobs. For a specific job, other jobs must be completed beforehand. While there are obviously many other constraints on processes, it is these on which we focussed for this research: how to allocate crews to jobs while satisfying job precedence requirements and personnel, and tooling and fixture (or, more generally, resource) requirements.

  20. Inhibitory effect of caffeic acid on ADP-induced thrombus formation and platelet activation involves mitogen-activated protein kinases

    PubMed Central

    Lu, Yu; Li, Quan; Liu, Yu-Ying; Sun, Kai; Fan, Jing-Yu; Wang, Chuan-She; Han, Jing-Yan

    2015-01-01

    Caffeic acid (CA), one of the active constituents of Radix Salvia miltiorrhizae, exhibits antioxidant and anti-inflammatory activities. However, few studies have assessed the ability of CA to inhibit platelet mediated thrombus generation in vivo. In this study, we investigated the antithrombotic effect of CA in mouse cerebral arterioles and venules using intravital microscopy. The antiplatelet activity of CA in ADP stimulated mouse platelets in vitro was also examined in attempt to explore the underlying mechanism. Our results demonstrated that CA (1.25–5 mg/kg) significantly inhibited thrombus formation in vivo. In vitro, CA (25–100 μM) inhibited ADP-induced platelet aggregation, P-selectin expression, ATP release, Ca2+ mobilization, and integrin αIIbβ3 activation. Additionally, CA attenuated p38, ERK, and JNK activation, and enhanced cAMP levels. Taken together, these data provide evidence for the inhibition of CA on platelet-mediated thrombosis in vivo, which is, at least partly, mediated by interference in phosphorylation of ERK, p38, and JNK leading to elevation of cAMP and down-regulation of P-selectin expression and αIIbβ3 activation. These results suggest that CA may have potential for the treatment of aberrant platelet activation-related diseases. PMID:26345207

  1. NASA revises shuttle schedule

    NASA Astrophysics Data System (ADS)

    Wainger, Lisa A.

    The new schedule for Space Shuttle missions and expendable launch vehicles (ELV's) calls for a 7-month delay in sending up the Hubble Space Telescope. NASA was forced to put off launching the telescope until February 1990 to keep the Magellan and Galileo missions within their narrow launch windows. The first post-Challenger shuttle launch is now scheduled for late this month. Discovery's most recent delays were due to a hydrogen leak discovered July 29 that has still not been corrected and an engine valve malfunction during an August 4 test fire.

  2. Intelligent retail logistics scheduling

    SciTech Connect

    Rowe, J.; Jewers, K.; Codd, A.; Alcock, A.

    1996-12-31

    The Supply Chain Integrated Ordering Network (SCION) Depot Bookings system automates the planning and scheduling of perishable and non-perishable commodities and the vehicles that carry them into J. Sainsbury depots. This is a strategic initiative, enabling the business to make the key move from weekly to daily ordering. The system is mission critical, managing the inwards flow of commodities from suppliers into J. Sainsbury`s depots. The system leverages Al techniques to provide a business solution that meets challenging functional and performance needs. The SCION Depot Bookings system is operational providing schedules for 22 depots across the UK.

  3. Multiple daily fractionation schedules

    SciTech Connect

    Peschel, R.E.; Fischer, J.J.

    1982-10-01

    Although conventional fractionation schedules have been satisfactory for the treatment of some tumors, there is reason to believe that the results of radiation therapy could be improved in some cases by appropriate alterations in treatment schedules. The pharmacological characteristics of some of the electron affinic radiation sensitizers have provided added incentive to investigate newer fractionation schemes, particularly ones which deliver the majority of the radiation dose in short periods of time. This editorial discusses three papers describing preliminary clinical studies using multi-daily fractionated (MDF) radiation therapy. Two of these studies also make use of the radiation sensitizer misonidazole. (KRM)

  4. Telmisartan prevention of LPS-induced microglia activation involves M2 microglia polarization via CaMKKβ-dependent AMPK activation.

    PubMed

    Xu, Yuan; Xu, Yazhou; Wang, Yurong; Wang, Yunjie; He, Ling; Jiang, Zhenzhou; Huang, Zhangjian; Liao, Hong; Li, Jia; Saavedra, Juan M; Zhang, Luyong; Pang, Tao

    2015-11-01

    Brain inflammation plays an important role in the pathophysiology of many psychiatric and neurological diseases. During brain inflammation, microglia cells are activated, producing neurotoxic molecules and neurotrophic factors depending on their pro-inflammatory M1 and anti-inflammatory M2 phenotypes. It has been demonstrated that Angiotensin II type 1 receptor blockers (ARBs) ameliorate brain inflammation and reduce M1 microglia activation. The ARB telmisartan suppresses glutamate-induced upregulation of inflammatory genes in cultured primary neurons. We wished to clarify whether telmisartan, in addition, prevents microglia activation through polarization to an anti-inflammatory M2 phenotype. We found that telmisartan promoted M2 polarization and reduced M1 polarization in LPS-stimulated BV2 and primary microglia cells, effects partially dependent on PPARγ activation. The promoting effects of telmisartan on M2 polarization, were attenuated by an AMP-activated protein kinase (AMPK) inhibitor or AMPK knockdown, indicating that AMPK activation participates on telmisartan effects. Moreover, in LPS-stimulated BV2 cells, telmisartan enhancement of M2 gene expression was prevented by the inhibitor STO-609 and siRNA of calmodulin-dependent protein kinase kinase β (CaMKKβ), an upstream kinase of AMPK. Furthermore, telmisartan enhanced brain AMPK activation and M2 gene expression in a mouse model of LPS-induced neuroinflammation. In addition, telmisartan reduced the LPS-induced sickness behavior in this in vivo model, and this effect was prevented by prior administration of an AMPK inhibitor. Our results indicate that telmisartan can be considered as a novel AMPK activator, suppressing microglia activation by promoting M2 polarization. Telmisartan may provide a novel, safe therapeutic approach to treat brain disorders associated with enhanced inflammation. PMID:26188187

  5. Possible dopaminergic stimulation of locus coeruleus alpha1-adrenoceptors involved in behavioral activation.

    PubMed

    Lin, Yan; Quartermain, David; Dunn, Adrian J; Weinshenker, David; Stone, Eric A

    2008-07-01

    alpha(1)-Adrenoceptors of the locus coeruleus (LC) have been implicated in behavioral activation in novel surroundings, but the endogenous agonist that activates these receptors has not been established. In addition to the canonical activation of alpha(1)-receptors by norepinephrine (NE), there is evidence that dopamine (DA) may also activate certain brain alpha(1)-receptors. This study examined the contribution of DA to exploratory activity in a novel cage by determining the effect of infusion of various dopaminergic and adrenergic drugs into the mouse LC. It was found that the D2/D3 agonist, quinpirole, which selectively blocks the release of CNS DA, produced a dose-dependent and virtually complete abolition of exploration and all movement in the novel cage test. The quinpirole-induced inactivity was significantly attenuated by coinfusion of DA but not by the D1 agonist, SKF38390. Furthermore, the DA attenuation of quinpirole inactivity was blocked by coinfusion of the alpha(1)-adrenergic receptor antagonist, terazosin, but not by the D1 receptor antagonist, SCH23390. LC infusions of either quinpirole or terazosin also produced profound inactivity in DA-beta-hydroxylase knockout (Dbh -/-) mice that lack NE, indicating that their behavioral effects were not due to an alteration of the release or action of LC NE. Measurement of endogenous DA, NE, and 5HT and their metabolites in the LC during exposure to the novel cage indicated an increase in the turnover of DA and NE but not 5HT. These results indicate that DA is a candidate as an endogenous agonist for behaviorally activating LC alpha(1)-receptors and may play a role in the activation of this nucleus by novel surroundings. PMID:18435418

  6. Anticonvulsant activity of Citrus aurantium blossom essential oil (neroli): involvment of the GABAergic system.

    PubMed

    Azanchi, Taravat; Shafaroodi, Hamed; Asgarpanah, Jinous

    2014-11-01

    Citrus aurantium L. blossoms are an important medicinal plant part in Iran and some other countries. It is used in traditional medicine as an antiseizure and anticonvulsant natural agent. Early in vitro research of the anticonvulsant activity of the blossom extracts were done but there has been no investigation focused on the blossom essential oil and its anticonvulsant activity. The anticonvulsant activity of the essential oil of C. aurantium blossoms (neroli) was investigated. The anticonvulsant activity of neroli was assessed in pentylenetetrazole (PTZ)-induced convulsion by i.v. and i.p. methods and maximal electroshock (MES) in mice, with diazepam as the standard drug. While mechanistic studies were conducted using flumazenil, a GABA A-benzodiazepine receptor complex site antagonist. Neroli produced protection against clonic by i.v adminiatration of PTZ at 20 and 40 mg/kg, compared with protection with benzodiazepine. The mean onset and percentage protection against convulsion in neroli-treated mice were reduced by flumazenil. Intraperitonaeal PTZ also decreased the latency of clonic seizure in the neroli (40 mg/kg) treated group. We also showed that neroli (20 and 40 mg/kg), exhibited inhibition of the tonic convulsion induced by MES and decreased the mortality rate. Neroli was analyzed by GC and GC-MS and twenty three constituents, representing 91.0 % of the chromatographical oil were identified. The major components of neroli were characterized as linalool (28.5%), linalyl acetate (19.6%), nerolidol (9.1%) E,E-farnesol (9.1%), α-terpineol (4.9%) and limonene (4.6%) which might be responsible for the anticonvulsant activity. The results suggest that neroli possesses biologically active constituent(s) that have anticonvulsant activity which supports the ethnomedicinal claims of the use of the plant in the management of seizure. PMID:25532295

  7. Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling

    PubMed Central

    Lin, Athena W.; Barradas, Marta; Stone, James C.; van Aelst, Linda; Serrano, Manuel; Lowe, Scott W.

    1998-01-01

    Oncogenic Ras transforms immortal rodent cells to a tumorigenic state, in part, by constitutively transmitting mitogenic signals through the mitogen-activated protein kinase (MAPK) cascade. In primary cells, Ras is initially mitogenic but eventually induces premature senescence involving the p53 and p16INK4a tumor suppressors. Constitutive activation of MEK (a component of the MAPK cascade) induces both p53 and p16, and is required for Ras-induced senescence of normal human fibroblasts. Furthermore, activated MEK permanently arrests primary murine fibroblasts but forces uncontrolled mitogenesis and transformation in cells lacking either p53 or INK4a. The precisely opposite response of normal and immortalized cells to constitutive activation of the MAPK cascade implies that premature senescence acts as a fail-safe mechanism to limit the transforming potential of excessive Ras mitogenic signaling. Consequently, constitutive MAPK signaling activates p53 and p16 as tumor suppressors. PMID:9765203

  8. Involvement of aberrant cyclin-dependent kinase 5/p25 activity in experimental traumatic brain injury.

    PubMed

    Yousuf, Mohammad A; Tan, Chunfeng; Torres-Altoro, Melissa I; Lu, Fang-Min; Plautz, Erik; Zhang, Shanrong; Takahashi, Masaya; Hernandez, Adan; Kernie, Steven G; Plattner, Florian; Bibb, James A

    2016-07-01

    Traumatic brain injury (TBI) is associated with adverse effects on brain functions, including sensation, language, emotions and/or cognition. Therapies for improving outcomes following TBI are limited. A better understanding of the pathophysiological mechanisms of TBI may suggest novel treatment strategies to facilitate recovery and improve treatment outcome. Aberrant activation of cyclin-dependent kinase 5 (Cdk5) has been implicated in neuronal injury and neurodegeneration. Cdk5 is a neuronal protein kinase activated via interaction with its cofactor p35 that regulates numerous neuronal functions, including synaptic remodeling and cognition. However, conversion of p35 to p25 via Ca(2+) -dependent activation of calpain results in an aberrantly active Cdk5/p25 complex that is associated with neuronal damage and cell death. Here, we show that mice subjected to controlled cortical impact (CCI), a well-established experimental TBI model, exhibit increased p25 levels and consistently elevated Cdk5-dependent phosphorylation of microtubule-associated protein tau and retinoblastoma (Rb) protein in hippocampal lysates. Moreover, CCI-induced neuroinflammation as indicated by increased astrocytic activation and number of reactive microglia. Brain-wide conditional Cdk5 knockout mice (Cdk5 cKO) subjected to CCI exhibited significantly reduced edema, ventricular dilation, and injury area. Finally, neurophysiological recordings revealed that CCI attenuated excitatory post-synaptic potential field responses in the hippocampal CA3-CA1 pathway 24 h after injury. This neurophysiological deficit was attenuated in Cdk5 cKO mice. Thus, TBI induces increased levels of p25 generation and aberrant Cdk5 activity, which contributes to pathophysiological processes underlying TBI progression. Hence, selectively preventing aberrant Cdk5 activity may be an effective acute strategy to improve recovery from TBI. Traumatic brain injury (TBI) increases astrogliosis and microglial activation

  9. Capsular Polysaccharide Is Involved in NLRP3 Inflammasome Activation by Klebsiella pneumoniae Serotype K1

    PubMed Central

    Yang, Feng-Ling; Chiu, Hsiao-Wen; Chou, Ju-Ching; Dong, Wei-Chih; Lin, Chien-Nan; Lin, Chai-Yi; Wang, Jin-Town; Li, Lan-Hui; Chiu, Huan-Wen; Chiu, Yi-Chich

    2015-01-01

    Klebsiella pneumoniae (strain 43816, K2 serotype) induces interleukin-1β (IL-1β) secretion, but neither the bacterial factor triggering the activation of these inflammasome-dependent responses nor whether they are mediated by NLRP3 or NLRC4 is known. In this study, we identified a capsular polysaccharide (K1-CPS) in K. pneumoniae (NTUH-K2044, K1 serotype), isolated from a primary pyogenic liver abscess (PLA K. pneumoniae), as the Klebsiella factor that induces IL-1β secretion in an NLRP3-, ASC-, and caspase-1-dependent manner in macrophages. K1-CPS induced NLRP3 inflammasome activation through reactive oxygen species (ROS) generation, mitogen-activated protein kinase phosphorylation, and NF-κB activation. Inhibition of both the mitochondrial membrane permeability transition and mitochondrial ROS generation inhibited K1-CPS-mediated NLRP3 inflammasome activation. Furthermore, IL-1β secretion in macrophages infected with PLA K. pneumoniae was shown to depend on NLRP3 but also on NLRC4 and TLR4. In macrophages infected with a K1-CPS deficiency mutant, an lipopolysaccharide (LPS) deficiency mutant, or K1-CPS and LPS double mutants, IL-1β secretion levels were lower than those in cells infected with wild-type PLA K. pneumoniae. Our findings indicate that K1-CPS is one of the Klebsiella factors of PLA K. pneumoniae that induce IL-1β secretion through the NLRP3 inflammasome. PMID:26077758

  10. Developing Science Communication in Africa: Undergraduate and Graduate Students should be Trained and Actively Involved in Outreach Activity Development and Implementation

    PubMed Central

    Karikari, Thomas K.; Yawson, Nat Ato; Quansah, Emmanuel

    2016-01-01

    Despite recent improvements in scientific research output from Africa, public understanding of science in many parts of the continent remains low. Science communication there is faced with challenges such as (i) lack of interest among some scientists, (ii) low availability of training programs for scientists, (iii) low literacy rates among the public, and (iv) multiplicity of languages. To address these challenges, new ways of training and motivating scientists to dialogue with non-scientists are essential. Developing communication skills early in researchers’ scientific career would be a good way to enhance their public engagement abilities. Therefore, a potentially effective means to develop science communication in Africa would be to actively involve trainee scientists (i.e., undergraduate and graduate students) in outreach activity development and delivery. These students are often enthusiastic about science, eager to develop their teaching and communication skills, and can be good mentors to younger students. Involving them in all aspects of outreach activity is, therefore, likely to be a productive implementation strategy. However, science communication training specifically for students and the involvement of these students in outreach activity design and delivery are lacking in Africa. Here, we argue that improving the training and involvement of budding scientists in science communication activities would be a good way to bridge the wide gap between scientists and the African public. PMID:27385932

  11. Developing Science Communication in Africa: Undergraduate and Graduate Students should be Trained and Actively Involved in Outreach Activity Development and Implementation.

    PubMed

    Karikari, Thomas K; Yawson, Nat Ato; Quansah, Emmanuel

    2016-01-01

    Despite recent improvements in scientific research output from Africa, public understanding of science in many parts of the continent remains low. Science communication there is faced with challenges such as (i) lack of interest among some scientists, (ii) low availability of training programs for scientists, (iii) low literacy rates among the public, and (iv) multiplicity of languages. To address these challenges, new ways of training and motivating scientists to dialogue with non-scientists are essential. Developing communication skills early in researchers' scientific career would be a good way to enhance their public engagement abilities. Therefore, a potentially effective means to develop science communication in Africa would be to actively involve trainee scientists (i.e., undergraduate and graduate students) in outreach activity development and delivery. These students are often enthusiastic about science, eager to develop their teaching and communication skills, and can be good mentors to younger students. Involving them in all aspects of outreach activity is, therefore, likely to be a productive implementation strategy. However, science communication training specifically for students and the involvement of these students in outreach activity design and delivery are lacking in Africa. Here, we argue that improving the training and involvement of budding scientists in science communication activities would be a good way to bridge the wide gap between scientists and the African public. PMID:27385932

  12. Teacher management behaviors and pupil task involvement during small group laboratory activities

    NASA Astrophysics Data System (ADS)

    Beasley, Warren

    A major concern of many beginning and experienced teachers is that of classroom management and control. This article describes recent research into defining classroom management procedures that are used by high school science teachers and their relationship to pupil ontaskness. The classroom is conceptualized as a manipulable behavioral system. This construct arises directly from Barker's (1968) ecological psychology, the classroom and its occupants being conceptualized as a behavior setting. The behaviors of the teacher and the pupils are an integral part of the unit (behavior setting), which in turn coerces certain behaviors from its participants. Thus settings, and, in particular, subsettings, are seen as more important determiners of social behavior than the personality of individual teacher or pupil. The methodology employed in this research has involved the extensive use of video in naturalistic science classrooms. Tapes of both teacher and pupil behaviors were continuously and independently recorded. Intensive analysis using electronic recording instruments interfaced with the computer has allowed the collection and sophisticated analysis of the observational data. Data relating to teacher management behavior in small group settings have been analyzed and the relationships to pupil task involvement have been explored.

  13. Transmembrane signal transduction in bacterial chemotaxis involves ligand-dependent activation of phosphate group transfer.

    PubMed Central

    Borkovich, K A; Kaplan, N; Hess, J F; Simon, M I

    1989-01-01

    Signal transduction in Escherichia coli involves the interaction of transmembrane receptor proteins such as the aspartate receptor, Tar, and the products of four chemotaxis genes, cheA, cheY, cheW, and cheZ. It was previously shown that the cheA gene product is an autophosphorylating protein kinase that transfers phosphate to CheY, whereas the cheZ gene product acts as a specific CheY phosphatase. Here we report that the system can be reconstituted in vitro and receptor function can be coupled to CheY phosphorylation. Coupling requires the presence of the CheW protein, the appropriate form of the receptor, and the CheA and CheY proteins. Under these conditions the accumulation of CheY-phosphate is enhanced approximately 300-fold. This rate enhancement is seen in reactions using wild-type and "tumble" mutant receptors but not "smooth" mutant receptors. The increased accumulation of phosphoprotein was inhibited by micromolar concentrations of aspartate, using wild-type, but not tumble, receptors. These results provide evidence that the signal transduction pathway in bacterial chemotaxis involves receptor-mediated alteration of the levels of phosphorylated proteins. They suggest that CheW acts as the coupling factor between receptor and phosphorylation. The results also support the suggestion that CheY-phosphate is the tumble signal. Images PMID:2645576

  14. NIK is involved in constitutive activation of the alternative NF-{kappa}B pathway and proliferation of pancreatic cancer cells

    SciTech Connect

    Nishina, Takashi; Yamaguchi, Noritaka; Gohda, Jin; Semba, Kentaro; Inoue, Jun-ichiro

    2009-10-09

    Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-{kappa}B is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-{kappa}B activation. Here, we show that the alternative pathway is constitutively activated and NF-{kappa}B-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

  15. Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation.

    PubMed

    Mohamad, Saharuddin B; Nagasawa, Hideko; Uto, Yoshihiro; Hori, Hitoshi

    2002-05-01

    Alpha-N-acetyl galactosaminidase (alpha-NaGalase) has been reported to accumulate in serum of cancer patients and be responsible for deglycosylation of Gc protein, which is a precursor of GcMAF-mediated macrophage activation cascade, finally leading to immunosuppression in advanced cancer patients. We studied the biochemical characterization of alpha-NaGalase from several human tumor cell lines. We also examined its effect on the potency of GcMAF to activate mouse peritoneal macrophage to produce superoxide in GcMAF-mediated macrophage activation cascade. The specific activity of alpha-NaGalases from human colon tumor cell line HCT116, human hepatoma cell line HepG2, and normal human liver cells (Chang liver cell line) were evaluated using two types of substrates; GalNAc-alpha-PNP (exo-type substrate) and Gal-beta-GalNAc-alpha-PNP (endo-type substrate). Tumor-derived alpha-NaGalase having higher activity than normal alpha-NaGalase, had higher substrate specificity to the exo-type substrate than to the endo-type substrate, and still maintained its activity at pH 7. GcMAF enhance superoxide production in mouse macrophage, and pre-treatment of GcMAF with tumor cell lysate reduce the activity. We conclude that tumor-derived alpha-NaGalase is different in biochemical characterization compared to normal alpha-NaGalase from normal Chang liver cells. In addition, tumor cell-derived alpha-NaGalase decreases the potency of GcMAF on macrophage activation. PMID:12062184

  16. The upstream activator CTF/NF1 and RNA polymerase II share a common element involved in transcriptional activation.

    PubMed Central

    Xiao, H; Lis, J T; Xiao, H; Greenblatt, J; Friesen, J D

    1994-01-01

    The carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II consists of tandem repeats of a heptapeptide with the consensus YSPTSPS. It has been shown that the heptapeptide repeat interacts directly with the general transcription factor TFIID. We report here that the CTD activates transcription when fused to the DNA-binding domain of GAL4. More importantly, we find that the proline-rich transcriptional activation domain of the CCAAT-box-binding factor CTF/NF1 contains a sequence with striking similarity to the heptapeptide repeats of the CTD. We show that this CTD-like motif is essential for the transcriptional activator function of the proline-rich domain of CTF/NF1. Deletion of and point mutations in this CTD-like motif abolish the transcriptional activator function of the proline-rich domain, while natural CTD repeats from RNA polymerase II are fully functional in place of the CTD-like motif. We further show that the proline-rich activation domain of CTF/NF1 interacts directly with the TATA-box-binding protein (TBP), and that a mutation in the CTD-like motif that abolishes transcriptional activation reduces the affinity of the proline-rich domain for TBP. These results demonstrate that a class of proline-rich activator proteins and RNA polymerase II possess a common structural and functional component which can interact with the same target in the general transcription machinery. We discuss the implications of these results for the mechanisms of transcriptional activation in eucaryotes. Images PMID:8029001

  17. Antiplasmodial activities of gold(I) complexes involving functionalized N-heterocyclic carbenes.

    PubMed

    Hemmert, Catherine; Ramadani, Arba Pramundita; Boselli, Luca; Fernández Álvarez, Álvaro; Paloque, Lucie; Augereau, Jean-Michel; Gornitzka, Heinz; Benoit-Vical, Françoise

    2016-07-01

    A series of twenty five molecules, including imidazolium salts functionalized by N-, O- or S-containing groups and their corresponding cationic, neutral or anionic gold(I) complexes were evaluated on Plasmodium falciparum in vitro and then on Vero cells to determine their selectivity. Among them, eight new compounds were synthesized and fully characterized by spectroscopic methods. The X-ray structures of three gold(I) complexes are presented. Except one complex (18), all the cationic gold(I) complexes show potent antiplasmodial activity with IC50 in the micro- and submicromolar range, correlated with their lipophilicity. Structure-activity relationships enable to evidence a lead-complex (21) displaying a good activity (IC50=210nM) close to the value obtained with chloroquine (IC50=514nM) and a weak cytotoxicity. PMID:27240469

  18. Phospholipase A{sub 2} is involved in the mechanism of activation of neutrophils by polychlorinated biphenyls

    SciTech Connect

    Tithof, P.K.; Schiamberg, E.; Ganey, P.E.; Peters-Golden, M.

    1996-01-01

    Aroclor 1242, a mixture of polychlorinated biphenyls (PCBs), activates neutrophils to produce superoxide anion (O{sub 2}{sup {minus}}) by a mechanism that involves phospholipase C-dependent hydrolysis of membrane phosphoinositides; however, subsequent signal transduction mechanisms are unknown. This study determines whether phospholipase A{sub 2}-dependent release of arachidonic acid is involved in PCB-induced O{sub 2}{sup {minus}} production. O{sub 2}{sup {minus}} production was measured in vitro in glycogen-elicited, rat neutrophils in the presence and absence of the inhibitors of phospholipase A{sub 2}: quinacrine, 4-bromophenacyl bromide (BPB), and manoalide. All three agents significantly decreased the amount of O{sub 2}{sup {minus}} detected during stimulation of neutrophils with Aroclor 1242. Similar inhibition occurred when neutrophils were activated with the classical stimuli, formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate. The effects of BPB and manoalide were not a result of cytotoxicity or other nonspecific effects. Significant release of {sup 3}H-arachidonic acid preceded O{sub 2}{sup {minus}} production in neutrophils stimulated with Aroclor 1242 or fMLP. Manoalide, at a concentration that abolished O{sub 2}{sup {minus}} production, also inhibited the release of {sup 3}H-arachidonate. Aspirin, zileuton, or WEB 2086 did not affect Aroclor 1242-induced O{sub 2}{sup {minus}} production, suggesting that eicosanoids and platelet-activating factor are not needed for neutrophil activation by PCBs. Activation of phos-pholipase A{sub 2} and O{sub 2}{sup {minus}} production do not appear to involve the Ah receptor. These data suggest that Aroclor 1242 stimulates neutrophils to produce O{sub 2}{sup {minus}} by a mechanism that involves phospholipase A{sub 2}-dependent release of arachiodonic acid. 49 refs., 6 figs., 2 tabs.

  19. Activation of soluble guanylyl cyclase by the nitrovasodilator 3-morpholinosydnonimine involves formation of S-nitrosoglutathione.

    PubMed

    Schrammel, A; Pfeiffer, S; Schmidt, K; Koesling, D; Mayer, B

    1998-07-01

    Soluble guanylyl cyclase (sGC) is the major physiological target of sydnonimine-based vasodilators such as molsidomine. Decomposition of sydnonimines results in the stoichiometric formation of nitric oxide (NO) and superoxide (O2-), which rapidly react to form peroxynitrite. Inasmuch as sGC is activated by NO but not by peroxynitrite, we investigated the mechanisms underlying sGC activation by 3-morpholinosydnonimine (SIN-1). Stimulation of purified bovine lung sGC by SIN-1 was found to be strongly dependent on glutathione (GSH). By contrast, GSH did not affect sGC activation by NO released from 2,2-diethyl-1-nitroso-oxyhydrazine, indicating that NO/O2- released from SIN-1 converted GSH to an activator of sGC. High performance liquid chromatography identified this product as the thionitrite S-nitrosoglutathione. Further, the reaction product decomposed to release NO upon addition of Cu(NO3)2 in the presence of GSH. Activation of sGC was antagonized by the Cu(I)-specific chelator neocuproine, whereas the Cu(II)-selective drug cuprizone was less potent. Carbon dioxide (delivered as NaHCO3) antagonized S-nitrosation by peroxynitrite but not by SIN-1. Thus, NO/O2- released from SIN-1 mediates a CO2-insensitive conversion of GSH to S-nitrosoglutathione, a thionitrite that activates sGC via trace metal-catalyzed release of NO. These results may provide novel insights into the molecular mechanism underlying the nitrovasodilator action of SIN-1. PMID:9658207

  20. Macrophages migrate in an activation-dependent manner to chemokines involved in neuroinflammation

    PubMed Central

    2014-01-01

    Background In neuroinflammatory diseases, macrophages can play a dual role in the process of tissue damage, depending on their activation status (M1 / M2). M1 macrophages are considered to exert damaging effects to neurons, whereas M2 macrophages are reported to aid regeneration and repair of neurons. Their migration within the central nervous system may be of critical importance in the final outcome of neurodegeneration in neuroinflammatory diseases e.g. multiple sclerosis (MS). To provide insight into this process, we examined the migratory capacity of human monocyte-derived M1 and M2 polarised macrophages towards chemoattractants, relevant for neuroinflammatory diseases like MS. Methods Primary cultures of human monocyte-derived macrophages were exposed to interferon gamma and lipopolysaccharide (LPS) to evoke proinflammatory (M1) activation or IL-4 to evoke anti-inflammatory (M2) activation. In a TAXIScan assay, migration of M0, M1 and M2 towards chemoattractants was measured and quantified. Furthermore the adhesion capacity and the expression levels of integrins as well as chemokine receptors of M0, M1 and M2 were assessed. Alterations in cell morphology were analysed using fluorescent labelling of the cytoskeleton. Results Significant differences were observed between M1 and M2 macrophages in the migration towards chemoattractants. We show that M2 macrophages migrated over longer distances towards CCL2, CCL5, CXCL10, CXCL12 and C1q compared to non-activated (M0) and M1 macrophages. No differences were observed in the adhesion of M0, M1 and M2 macrophages to multiple matrix components, nor in the expression of integrins and chemokine receptors. Significant changes were observed in the cytoskeleton organization upon stimulation with CCL2, M0, M1 and M2 macrophages adopt a spherical morphology and the cytoskeleton is rapidly rearranged. M0 and M2 macrophages are able to form filopodia, whereas M1 macrophages only adapt a spherical morphology. Conclusions