Sample records for key components responsible

  1. Second-order schedules: discrimination of components1

    PubMed Central

    Squires, Nancy; Norborg, James; Fantino, Edmund

    1975-01-01

    Pigeons were exposed to a series of second-order schedules in which the completion of a fixed number of fixed-interval components produced food. In Experiment 1, brief (2 sec) stimulus presentations occurred as each fixed-interval component was completed. During the brief-stimulus presentation terminating the last fixed-interval component, a response was required on a second key, the brief-stimulus key, to produce food. Responses on the brief-stimulus key before the last brief-stimulus presentation had no scheduled consequences, but served as a measure of the extent to which the final component was discriminated from preceding components. Whether there were one, two, four, or eight fixed-interval components, responses on the brief-stimulus key occurred during virtually every brief-stimulus presentation. In Experiment 2, an attempt was made to punish unnecessary responses on the brief-stimulus key, i.e., responses on the brief-stimulus key that occurred before the last component. None of the pigeons learned to withhold these responses, even though they produced a 15-sec timeout and loss of primary reinforcement. In Experiment 3, different key colors were associated with each component of a second-order schedule (a chain schedule). In contrast to Experiment 1, brief-stimulus key responses were confined to the last component. It was concluded that pigeons do not discriminate well between components of second-order schedules unless a unique exteroceptive cue is provided for each component. The relative discriminability of the components may account for the observed differences in initial-component response rates between comparable brief-stimulus, tandem, and chain schedules. PMID:16811868

  2. Key-peck durations under behavioral contrast and differential reinforcement

    PubMed Central

    Whipple, William R.; Fantino, Edmund

    1980-01-01

    Pigeons were maintained on a multiple schedule in which both components were variable-interval one-minute schedules. When they were switched to a condition in which one component was extinction, behavioral contrast was observed. The median durations of the key pecks in the unchanged component did not decrease in size. The results are incompatible with a theory of behavioral contrast which considers the added pecks to be short-duration responses. In a second experiment, pigeons were required to emit short-duration key pecks in one component of a multiple schedule, and long-duration pecks in the other. Two of three pigeons learned to emit responses appropriate to the requirements of the component in effect, suggesting that the duration of the key-peck response is sensitive to differential reinforcement. PMID:16812185

  3. Combinations of Response-Dependent and Response-Independent Schedule-Correlated Stimulus Presentation in an Observing Procedure

    ERIC Educational Resources Information Center

    DeFulio, Anthony; Hackenberg, Timothy D.

    2008-01-01

    Pigeons pecked a response key on a variable-interval (VI) schedule, in which responses produced food every 40 s, on average. These VI periods, or components, alternated in irregular fashion with extinction components in which food was unavailable. Pecks on a second (observing) key briefly produced exteroceptive stimuli (houselight flashes)…

  4. Autoshaping the pigeon's gape response: acquisition and topography as a function of reinforcer type and magnitude.

    PubMed Central

    Allan, R W; Zeigler, H P

    1994-01-01

    The pigeon's key-pecking response is experimentally dissociable into transport (head movement) and gape (jaw movement) components. During conditioning of the key-pecking response, both components come under the control of the conditioned stimulus. To study the acquisition of gape conditioned responses and to clarify the contribution of unconditioned stimulus (reinforcer) variables to the form of the response, gape and key-contact responses were recorded during an autoshaping procedure and reinforcer properties were systematically varied. One group of 8 pigeons was food deprived and subgroups of 2 birds each were exposed to four different pellet sizes as reinforcers, each reinforcer signaled by a keylight conditioned stimulus. A second group was water deprived and received water reinforcers paired with the conditioned stimulus. Water- or food-deprived control groups received appropriate water or food reinforcers that were randomly delivered with respect to the keylight stimulus. Acquisition of the conditioned gape response frequently preceded key-contact responses, and gape conditioned responses were generally elicited at higher rates than were key contacts. The form of the conditioned gape was similar to, but not identical with, the form of the unconditioned gape. The gape component is a critical topographical feature of the conditioned key peck, a sensitive measure of conditioning during autoshaping, and an important source of the observed similarities in the form of conditioned and consummatory responses. PMID:7964365

  5. Autoshaping the pigeon's gape response: acquisition and topography as a function of reinforcer type and magnitude.

    PubMed

    Allan, R W; Zeigler, H P

    1994-09-01

    The pigeon's key-pecking response is experimentally dissociable into transport (head movement) and gape (jaw movement) components. During conditioning of the key-pecking response, both components come under the control of the conditioned stimulus. To study the acquisition of gape conditioned responses and to clarify the contribution of unconditioned stimulus (reinforcer) variables to the form of the response, gape and key-contact responses were recorded during an autoshaping procedure and reinforcer properties were systematically varied. One group of 8 pigeons was food deprived and subgroups of 2 birds each were exposed to four different pellet sizes as reinforcers, each reinforcer signaled by a keylight conditioned stimulus. A second group was water deprived and received water reinforcers paired with the conditioned stimulus. Water- or food-deprived control groups received appropriate water or food reinforcers that were randomly delivered with respect to the keylight stimulus. Acquisition of the conditioned gape response frequently preceded key-contact responses, and gape conditioned responses were generally elicited at higher rates than were key contacts. The form of the conditioned gape was similar to, but not identical with, the form of the unconditioned gape. The gape component is a critical topographical feature of the conditioned key peck, a sensitive measure of conditioning during autoshaping, and an important source of the observed similarities in the form of conditioned and consummatory responses.

  6. Keys and seats: Spatial response coding underlying the joint spatial compatibility effect.

    PubMed

    Dittrich, Kerstin; Dolk, Thomas; Rothe-Wulf, Annelie; Klauer, Karl Christoph; Prinz, Wolfgang

    2013-11-01

    Spatial compatibility effects (SCEs) are typically observed when participants have to execute spatially defined responses to nonspatial stimulus features (e.g., the color red or green) that randomly appear to the left and the right. Whereas a spatial correspondence of stimulus and response features facilitates response execution, a noncorrespondence impairs task performance. Interestingly, the SCE is drastically reduced when a single participant responds to one stimulus feature (e.g., green) by operating only one response key (individual go/no-go task), whereas a full-blown SCE is observed when the task is distributed between two participants (joint go/no-go task). This joint SCE (a.k.a. the social Simon effect) has previously been explained by action/task co-representation, whereas alternative accounts ascribe joint SCEs to spatial components inherent in joint go/no-go tasks that allow participants to code their responses spatially. Although increasing evidence supports the idea that spatial rather than social aspects are responsible for joint SCEs emerging, it is still unclear to which component(s) the spatial coding refers to: the spatial orientation of response keys, the spatial orientation of responding agents, or both. By varying the spatial orientation of the responding agents (Exp. 1) and of the response keys (Exp. 2), independent of the spatial orientation of the stimuli, in the present study we found joint SCEs only when both the seating and the response key alignment matched the stimulus alignment. These results provide evidence that spatial response coding refers not only to the response key arrangement, but also to the-often neglected-spatial orientation of the responding agents.

  7. Drug discrimination under two concurrent fixed-interval fixed-interval schedules.

    PubMed

    McMillan, D E; Li, M

    2000-07-01

    Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-interval (FI) 100-s FI 200-s schedule of food presentation, and later tinder a concurrent FI 40-s FI 80-s schedule, in which the FI component with the shorter time requirement reinforced responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized under the concurrent FI 100-s FI 200-s schedule, pigeons earned an average of 66% (after pentobarbital) to 68% (after saline) of their reinforcers for responding under the FI 100-s component of the concurrent schedule. These birds made an average of 70% of their responses on both the pentobarbital-biased key after the training dose of pentobarbital and the saline-biased key after saline. After responding stabilized under the concurrent FI 40-s FI 80-s schedule, pigeons earned an average of 67% of their reinforcers for responding under the FI 40 component after both saline and the training dose of pentobarbital. These birds made an average of 75% of their responses on the pentobarbital-biased key after the training dose of pentobarbital, but only 55% of their responses on the saline-biased key after saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, ethanol, phencyclidine, or methamphetamine, the dose-response curves were similar under these two concurrent schedules. Pentobarbital, chlordiazepoxide, and ethanol produced dose-dependent increases in responding on the pentobarbital-biased key as the doses increased. For some birds, at the highest doses of these drugs, the dose-response curve turned over. Increasing doses of phencyclidine produced increased responding on the pentobarbital-biased key in some, but not all, birds. After methamphetamine, responding was largely confined to the saline-biased key. These data show that pigeons can perform drug discriminations under concurrent schedules in which the reinforcement frequency under the schedule components differs only by a factor of two, and that when other drugs are substituted for the training drugs they produce dose-response curves similar to the curves produced by these drugs under other concurrent interval schedules.

  8. Framework for a U.S. Geological Survey Hydrologic Climate-Response Program in Maine

    USGS Publications Warehouse

    Hodgkins, Glenn A.; Lent, Robert M.; Dudley, Robert W.; Schalk, Charles W.

    2009-01-01

    This report presents a framework for a U.S. Geological Survey (USGS) hydrologic climate-response program designed to provide early warning of changes in the seasonal water cycle of Maine. Climate-related hydrologic changes on Maine's rivers and lakes in the winter and spring during the last century are well documented, and several river and lake variables have been shown to be sensitive to air-temperature changes. Monitoring of relevant hydrologic data would provide important baseline information against which future climate change can be measured. The framework of the hydrologic climate-response program presented here consists of four major parts: (1) identifying homogeneous climate-response regions; (2) identifying hydrologic components and key variables of those components that would be included in a hydrologic climate-response data network - as an example, streamflow has been identified as a primary component, with a key variable of streamflow being winter-spring streamflow timing; the data network would be created by maintaining existing USGS data-collection stations and establishing new ones to fill data gaps; (3) regularly updating historical trends of hydrologic data network variables; and (4) establishing basins for process-based studies. Components proposed for inclusion in the hydrologic climate-response data network have at least one key variable for which substantial historical data are available. The proposed components are streamflow, lake ice, river ice, snowpack, and groundwater. The proposed key variables of each component have extensive historical data at multiple sites and are expected to be responsive to climate change in the next few decades. These variables are also important for human water use and (or) ecosystem function. Maine would be divided into seven climate-response regions that follow major river-basin boundaries (basins subdivided to hydrologic units with 8-digit codes or larger) and have relatively homogeneous climates. Key hydrologic variables within each climate-response region would be analyzed regularly to maintain up-to-date analyses of year-to-year variability, decadal variability, and longer term trends. Finally, one basin in each climate-response region would be identified for process-based hydrologic and ecological studies.

  9. Does the context of reinforcement affect resistance to change?

    PubMed

    Nevin, J A; Grace, R C

    1999-04-01

    Eight pigeons were trained on multiple schedules of reinforcement where pairs of components alternated in blocks on different keys to define 2 local contexts. On 1 key, components arranged 160 and 40 reinforcers/hr; on the other, components arranged 40 and 10 reinforcers/hr. Response rates in the 40/hr component were higher in the latter pair. Within pairs, resistance to prefeeding and resistance to extinction were generally greater in the richer component. The two 40/hr components did not differ in resistance to prefeeding, but the 40/hr component that alternated with 10/hr was more resistant to extinction. This discrepancy was interpreted by an algebraic model relating response strength to component reinforcer rate, including generalization decrement. According to this model, strength is independent of context, consistent with research on schedule preference.

  10. Resistance to reinforcement change in multiple and concurrent schedules assessed in transition and at steady state.

    PubMed

    McLean, A P; Blampied, N M

    1995-01-01

    Behavioral momentum theory relates resistance to change of responding in a multiple-schedule component to the total reinforcement obtained in that component, regardless of how the reinforcers are produced. Four pigeons responded in a series of multiple-schedule conditions in which a variable-interval 40-s schedule arranged reinforcers for pecking in one component and a variable-interval 360-s schedule arranged them in the other. In addition, responses on a second key were reinforced according to variable-interval schedules that were equal in the two components. In different parts of the experiment, responding was disrupted by changing the rate of reinforcement on the second key or by delivering response-independent food during a blackout separating the two components. Consistent with momentum theory, responding on the first key in Part 1 changed more in the component with the lower reinforcement total when it was disrupted by changes in the rate of reinforcement on the second key. However, responding on the second key changed more in the component with the higher reinforcement total. In Parts 2 and 3, responding was disrupted with free food presented during intercomponent blackouts, with extinction (Part 2) or variable-interval 80-s reinforcement (Part 3) arranged on the second key. Here, resistance to change was greater for the component with greater overall reinforcement. Failures of momentum theory to predict short-term differences in resistance to change occurred with disruptors that caused greater change between steady states for the richer component. Consistency of effects across disruptors may yet be found if short-term effects of disruptors are assessed relative to the extent of change observed after prolonged exposure.

  11. WRKY Transcription Factors: Key Components in Abscisic Acid Signaling

    DTIC Science & Technology

    2011-01-01

    Review article WRKY transcription factors : key components in abscisic acid signalling Deena L. Rushton1, Prateek Tripathi1, Roel C. Rabara1, Jun Lin1...May 2011. *Correspondence (Tel +605 688 5749; fax +605 688 5624; email paul.rushton@sdstate.edu) Keywords: abscisic acid, WRKY transcription factor ...seed germination, drought, abiotic stress. Summary WRKY transcription factors (TFs) are key regulators of many plant processes, including the responses

  12. Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

    PubMed

    Sato, Takeo; Maekawa, Shugo; Konishi, Mineko; Yoshioka, Nozomi; Sasaki, Yuki; Maeda, Haruna; Ishida, Tetsuya; Kato, Yuki; Yamaguchi, Junji; Yanagisawa, Shuichi

    2017-01-29

    Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Plant responses to simulated hurricane impacts in a subtropical wet forest, Puerto Rico

    Treesearch

    Aaron B. Shiels; Jess K. Zimmerman; Diana C. García-Montiel; Inge Jonckheere; Jennifer Holm; David Horton; Nicholas Brokaw

    2010-01-01

    1. We simulated two key components of severe hurricane disturbance, canopy openness and detritus deposition, to determine the independent and interactive effects of these components on woody plant recruitment and forest structure. 2. We increased canopy openness by trimming branches and added or subtracted canopy detritus in a factorial design. Plant responses were...

  14. About the National Center for Radiation Field Operations (NCRFO)

    EPA Pesticide Factsheets

    The National Center for Radiation Field Operations (NCRFO) is an essential component of EPA’s Radiological Emergency Response Team (RERT) and is key to EPA's response to radiological emergencies and accidents nationwide.

  15. Biomarkers for diet and cancer prevention research: potentials and challenges.

    PubMed

    Davis, Cindy D; Milner, John A

    2007-09-01

    As cancer incidence is projected to increase for decades there is a need for effective preventive strategies. Fortunately, evidence continues to mount that altering dietary habits is an effective and cost-efficient approach for reducing cancer risk and for modifying the biological behavior of tumors. Predictive, validated and sensitive biomarkers, including those that reliably evaluate "intake" or exposure to a specific food or bioactive component, that assess one or more specific biological "effects" that are linked to cancer, and that effectively predict individual "susceptibility" as a function of nutrient-nutrient interactions and genetics, are fundamental to evaluating who will benefit most from dietary interventions. These biomarkers must be readily accessible, easily and reliably assayed, and predictive of a key process(es) involved in cancer. The response to a food is determined not only by the effective concentration of the bioactive food component(s) reaching the target tissue, but also by the amount of the target requiring modification. Thus, this threshold response to foods and their components will vary from individual to individual. The key to understanding a personalized response is a greater knowledge of nutrigenomics, proteomics and metabolomics.

  16. Resistance to Change and Preference for Variable versus Fixed Response Sequences

    ERIC Educational Resources Information Center

    Arantes, Joana; Berg, Mark E.; Le, Dien; Grace, Randolph C.

    2012-01-01

    In Experiment 1, 4 pigeons were trained on a multiple chain schedule in which the initial link was a variable-interval (VI) 20-s schedule signalled by a red or green center key, and terminal links required four responses made to the left (L) and/or right (R) keys. In the REPEAT component, signalled by red keylights, only LRLR terminal-link…

  17. COMPREHENSIVE RESPONSES OF LIPID CLASSES TO TOXIANTS AND INVOLVEMENT IN DISEASES

    EPA Science Inventory

    Along with genes and proteins, lipids are a key component of the cellular metabolome. Lipids can mediate the induction of some diseases such as atherosclerosis and also responses to some diseases, e.g., asthma. Pollutants such as ozone appear to induce biological responses throug...

  18. Resistance to Change and Relapse of Observing

    PubMed Central

    Thrailkill, Eric A; Shahan, Timothy A

    2012-01-01

    Four experiments examined relapse of extinguished observing behavior of pigeons using a two-component multiple schedule of observing-response procedures. In both components, unsignaled periods of variable-interval (VI) food reinforcement alternated with extinction and observing responses produced stimuli associated with the availability of the VI schedule (i.e., S+). The components differed in the rate of food arranged (Rich  = VI 30 s; Lean  =  VI 120 s). In Experiment 1, following baseline training, extinction of observing involved removal of both food and S+ deliveries, and reinstatement was examined by presenting either response-independent food or S+ deliveries. In Experiment 2, extinction involved removal of only food deliveries while observing responses continued to produce S+. Reinstatement was examined by delivering food contingent upon the first two food-key responses occurring in the presence of the S+. Experiment 3 assessed ABA renewal of observing by extinguishing food-key and observing responses in the presence of one contextual stimulus (i.e., B) and then returning to the original training context (i.e., A) during continued extinction. Experiment 4 examined resurgence by introducing food reinforcement for an alternative response during extinction, and subsequently removing that alternative source of food. Across experiments, relative resistance to extinction and relapse of observing tended to be greater in the component previously associated with the higher rate of primary reinforcement. Relapse of observing or attending to stimuli associated with primary reinforcement appears to be impacted by frequency of primary reinforcement in a manner similar to responding maintained directly by primary reinforcement. PMID:22693359

  19. Mechanisms of fibrosis: therapeutic translation for fibrotic disease

    PubMed Central

    Wynn, Thomas A; Ramalingam, Thirumalai R

    2012-01-01

    Fibrosis is a pathological feature of most chronic inflammatory diseases. Fibrosis, or scarring, is defined by the accumulation of excess extracellular matrix components. If highly progressive, the fibrotic process eventually leads to organ malfunction and death. Fibrosis affects nearly every tissue in the body. Here we discuss how key components of the innate and adaptive immune response contribute to the pathogenesis of fibrosis. We also describe how cell-intrinsic changes in important structural cells can perpetuate the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix–producing myofibroblasts. Finally, we highlight some of the key mechanisms and pathways of fibrosis that are being targeted as potential therapies for a variety of important human diseases. PMID:22772564

  20. 33 CFR 155.1040 - Response plan requirements for unmanned tank barges carrying oil as a primary cargo.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...

  1. 33 CFR 155.1040 - Response plan requirements for unmanned tank barges carrying oil as a primary cargo.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...

  2. 33 CFR 155.1035 - Response plan requirements for manned vessels carrying oil as a primary cargo.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... be used to manage the response actions. This structure must include the following functional areas and must further include information for key components within each functional area: (i) Command and... operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The responsibilities of, duties...

  3. 33 CFR 155.1040 - Response plan requirements for unmanned tank barges carrying oil as a primary cargo.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...

  4. 33 CFR 155.1035 - Response plan requirements for manned vessels carrying oil as a primary cargo.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... be used to manage the response actions. This structure must include the following functional areas and must further include information for key components within each functional area: (i) Command and... operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The responsibilities of, duties...

  5. 33 CFR 155.1040 - Response plan requirements for unmanned tank barges carrying oil as a primary cargo.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...

  6. 33 CFR 155.1035 - Response plan requirements for manned vessels carrying oil as a primary cargo.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... be used to manage the response actions. This structure must include the following functional areas and must further include information for key components within each functional area: (i) Command and... operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The responsibilities of, duties...

  7. 33 CFR 155.1035 - Response plan requirements for manned vessels carrying oil as a primary cargo.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... be used to manage the response actions. This structure must include the following functional areas and must further include information for key components within each functional area: (i) Command and... operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The responsibilities of, duties...

  8. Recent advances in understanding vitiligo.

    PubMed

    Manga, Prashiela; Elbuluk, Nada; Orlow, Seth J

    2016-01-01

    Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-γ/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.

  9. Combinations of response-reinforcer relations in periodic and aperiodic schedules.

    PubMed

    Kuroda, Toshikazu; Cançado, Carlos R X; Lattal, Kennon A; Elcoro, Mirari; Dickson, Chata A; Cook, James E

    2013-03-01

    Key pecking of 4 pigeons was studied under a two-component multiple schedule in which food deliveries were arranged according to a fixed and a variable interfood interval. The percentage of response-dependent food in each component was varied, first in ascending (0, 10, 30, 70 and 100%) and then in descending orders, in successive conditions. The change in response rates was positively related to the percentage of response-dependent food in each schedule component. Across conditions, positively accelerated and linear patterns of responding occurred consistently in the fixed and variable components, respectively. These results suggest that the response-food dependency determines response rates in periodic and aperiodic schedules, and that the temporal distribution of food determines response patterns independently of the response-food dependency. Running rates, but not postfood pauses, also were positively related to the percentage of dependent food in each condition, in both fixed and variable components. Thus, the relation between overall response rate and the percentage of dependent food was mediated by responding that occurred after postfood pausing. The findings together extend previous studies wherein the dependency was either always present or absent, and increase the generality of the effects of variations in the response-food dependency from aperiodic to periodic schedules. © Society for the Experimental Analysis of Behavior.

  10. Postsuicide Intervention as a Prevention Tool: Developing a Comprehensive Campus Response to Suicide and Related Risk

    ERIC Educational Resources Information Center

    Cimini, M. Dolores; Rivero, Estela M.

    2013-01-01

    This chapter explores the critical role of crisis intervention and other support after a suicide has occurred as part of a comprehensive suicide prevention response within college and university campuses. The important components of postsuicide intervention campus crisis response and protocols and the identification of key stakeholders to…

  11. Do Conditional Reinforcers Count?

    PubMed Central

    Davison, Michael; Baum, William M

    2006-01-01

    Six pigeons were trained on a procedure in which seven components arranged different food-delivery ratios on concurrent variable-interval schedules each session. The components were unsignaled, lasted for 10 food deliveries, and occurred in random order with a 60-s blackout between components. The schedules were arranged using a switching-key procedure in which two responses on a center key changed the schedules and associated stimuli on two side keys. In Experiment 1, over five conditions, an increasing proportion of food deliveries accompanied by a magazine light was replaced with the presentation of the magazine light only. Local analyses of preference showed preference pulses toward the alternative that had just produced either a food-plus-magazine-light or magazine-light-only presentation, but pulses after food deliveries were always greater than those after magazine lights. Increasing proportions of magazine lights did not change the size of preference pulses after food or magazine-light presentations. Experiment 2 investigated the effects of correlations between food ratios and magazine-light ratios: In Condition 6, magazine-light ratios in components were inversely correlated (−1.0) with food ratios, and in Condition 7, magazine-light ratios were uncorrelated with food ratios. In Conditions 8 and 9, pecks also produced occasional 2.5-s flashes of a green keylight. In Condition 8, food and magazine-light ratios were correlated 1.0 whereas food and green-key ratios were correlated −1.0. In Condition 9, food and green-key ratios were correlated 1.0 whereas food and magazine-light ratios were correlated −1.0. Preference pulses toward alternatives after magazine lights and green keys depended on the correlation between these event ratios and the food ratios: If the ratios were correlated +1.0, positive preference pulses resulted; if the correlation was −1.0, preference pulses were negative. These results suggest that the Law of Effect has more to do with events signaling consequences than with strengthening responses. PMID:17191753

  12. 33 CFR 155.1045 - Response plan requirements for vessels carrying oil as a secondary cargo.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... must include the following functional areas and must further include information for key components within each functional area: (i) Command and control; (ii) Public information; (iii) Safety; (iv) Liaison with government agencies; (v) Spill response operations; (vi) Planning; (vii) Logistics support; and...

  13. 33 CFR 155.1045 - Response plan requirements for vessels carrying oil as a secondary cargo.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... must include the following functional areas and must further include information for key components within each functional area: (i) Command and control; (ii) Public information; (iii) Safety; (iv) Liaison with government agencies; (v) Spill response operations; (vi) Planning; (vii) Logistics support; and...

  14. 33 CFR 155.1045 - Response plan requirements for vessels carrying oil as a secondary cargo.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... must include the following functional areas and must further include information for key components within each functional area: (i) Command and control; (ii) Public information; (iii) Safety; (iv) Liaison with government agencies; (v) Spill response operations; (vi) Planning; (vii) Logistics support; and...

  15. 33 CFR 155.1045 - Response plan requirements for vessels carrying oil as a secondary cargo.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... must include the following functional areas and must further include information for key components within each functional area: (i) Command and control; (ii) Public information; (iii) Safety; (iv) Liaison with government agencies; (v) Spill response operations; (vi) Planning; (vii) Logistics support; and...

  16. Stimulus Effects on Local Preference: Stimulus-Response Contingencies, Stimulus-Food Pairing, and Stimulus-Food Correlation

    ERIC Educational Resources Information Center

    Davison, Michael; Baum, William M.

    2010-01-01

    Four pigeons were trained in a procedure in which concurrent-schedule food ratios changed unpredictably across seven unsignaled components after 10 food deliveries. Additional green-key stimulus presentations also occurred on the two alternatives, sometimes in the same ratio as the component food ratio, and sometimes in the inverse ratio. In eight…

  17. Seven-year responses of trees to experimental hurricane effects in a tropical rainforest, Puerto Rico

    Treesearch

    Jess K. Zimmerman; James Aaron Hogan; Aaron B. Shiels; John E. Bithorn; Samuel Matta Carmona; Nicholas Brokaw

    2014-01-01

    We experimentally manipulated key components of severe hurricane disturbance, canopy openness and detritus deposition, to determine the independent and interactive effects of these components on tree recruitment, forest structure, and diversity in a wet tropical forest in the Luquillo Experimental Forest, Puerto Rico. Canopy openness was increased by trimming branches...

  18. Advanced Photon Source lights the way to 2012 Chemistry Nobel | Argonne

    Science.gov Websites

    cascade of different cellular processes in response. They constitute key components of how cells interact the human β2 adrenoreceptor (β2AR), is responsible for a number of different biological responses . The receptor is in magenta while the different G protein subunits are colored green, red and blue

  19. Plant salt-tolerance mechanisms

    DOE PAGES

    Deinlein, Ulrich; Stephan, Aaron B.; Horie, Tomoaki; ...

    2014-06-01

    Crop performance is severely affected by high salt concentrations in soils. To engineer more salt-tolerant plants it is crucial to unravel the key components of the plant salt-tolerance network. Here we review our understanding of the core salt-tolerance mechanisms in plants. Recent studies have shown that stress sensing and signaling components can play important roles in regulating the plant salinity stress response. We also review key Na+ transport and detoxification pathways and the impact of epigenetic chromatin modifications on salinity tolerance. In addition, we discuss the progress that has been made towards engineering salt tolerance in crops, including marker-assisted selectionmore » and gene stacking techniques. We also identify key open questions that remain to be addressed in the future.« less

  20. The Response to High CO2 Levels Requires the Neuropeptide Secretion Component HID-1 to Promote Pumping Inhibition

    PubMed Central

    Sharabi, Kfir; Charar, Chayki; Friedman, Nurit; Mizrahi, Inbar; Zaslaver, Alon; Sznajder, Jacob I.; Gruenbaum, Yosef

    2014-01-01

    Carbon dioxide (CO2) is a key molecule in many biological processes; however, mechanisms by which organisms sense and respond to high CO2 levels remain largely unknown. Here we report that acute CO2 exposure leads to a rapid cessation in the contraction of the pharynx muscles in Caenorhabditis elegans. To uncover the molecular mechanisms underlying this response, we performed a forward genetic screen and found that hid-1, a key component in neuropeptide signaling, regulates this inhibition in muscle contraction. Surprisingly, we found that this hid-1-mediated pathway is independent of any previously known pathways controlling CO2 avoidance and oxygen sensing. In addition, animals with mutations in unc-31 and egl-21 (neuropeptide secretion and maturation components) show impaired inhibition of muscle contraction following acute exposure to high CO2 levels, in further support of our findings. Interestingly, the observed response in the pharynx muscle requires the BAG neurons, which also mediate CO2 avoidance. This novel hid-1-mediated pathway sheds new light on the physiological effects of high CO2 levels on animals at the organism-wide level. PMID:25101962

  1. 33 CFR 155.5035 - Nontank vessel response plan requirements: Specific content.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-hour basis; (3) A list of the Captain of the Port (COTP) zones, ports, and offshore transit areas in... areas and information for key components within each functional area— (i) Command and control; (ii...; (vi) Planning; (vii) Logistics support; and (viii) Finance; and (5) The responsibilities and duties of...

  2. Studies in Mathematics Education, Volume 3. The Mathematical Education of Primary-School Teachers.

    ERIC Educational Resources Information Center

    Morris, Robert, Ed.

    Recognizing that the teacher is the key to improving any mathematics program, this volume examines the responsibility of primary school teachers for the mathematics component of the curriculum and the implications thereof for teacher education. The first two chapters focus on the responsibilities of teachers of primary mathematics and contemporary…

  3. Programmable chemical reaction networks: emulating regulatory functions in living cells using a bottom-up approach.

    PubMed

    van Roekel, Hendrik W H; Rosier, Bas J H M; Meijer, Lenny H H; Hilbers, Peter A J; Markvoort, Albert J; Huck, Wilhelm T S; de Greef, Tom F A

    2015-11-07

    Living cells are able to produce a wide variety of biological responses when subjected to biochemical stimuli. It has become apparent that these biological responses are regulated by complex chemical reaction networks (CRNs). Unravelling the function of these circuits is a key topic of both systems biology and synthetic biology. Recent progress at the interface of chemistry and biology together with the realisation that current experimental tools are insufficient to quantitatively understand the molecular logic of pathways inside living cells has triggered renewed interest in the bottom-up development of CRNs. This builds upon earlier work of physical chemists who extensively studied inorganic CRNs and showed how a system of chemical reactions can give rise to complex spatiotemporal responses such as oscillations and pattern formation. Using purified biochemical components, in vitro synthetic biologists have started to engineer simplified model systems with the goal of mimicking biological responses of intracellular circuits. Emulation and reconstruction of system-level properties of intracellular networks using simplified circuits are able to reveal key design principles and molecular programs that underlie the biological function of interest. In this Tutorial Review, we present an accessible overview of this emerging field starting with key studies on inorganic CRNs followed by a discussion of recent work involving purified biochemical components. Finally, we review recent work showing the versatility of programmable biochemical reaction networks (BRNs) in analytical and diagnostic applications.

  4. The dimensions of responsiveness of a health system: a Taiwanese perspective.

    PubMed

    Hsu, Chih-Cheng; Chen, Likwang; Hu, Yu-Whuei; Yip, Winnie; Shu, Chen-Chun

    2006-03-17

    Responsiveness is an indicator used to measure how well a health system performs relative to non-health aspects. This study assessed whether seven dimensions proposed by the World Health Organization (WHO) to measure responsiveness (dignity, autonomy, confidentiality, prompt attention, social support, basic amenities, and choices of providers) are applicable in evaluating the health system of Taiwan. A key informant survey and focus group research were used in this study. The translated WHO proposed questionnaire was sent to 205 nominated key informants by mail, and 132 (64.4%) were returned. We used principal component analysis to extract factors. Linear regression analysis was used to assess the relationship between the total score and the extracted factors. A qualitative content analysis was also carried out in focus group research. Principal component analysis produced five factors (respect, access, confidentiality, basic amenities, and social support) that explained 63.5% of the total variances. These five factors demonstrated acceptable internal consistency and four of them (except social support) were significantly correlated with the total responsiveness score. The focus group interviews revealed health providers' communication ability and medical ethics were also highly appraised by Taiwanese. When the performance of a health system is to be evaluated, elements of responsiveness proposed by WHO may have to be tailored to fit different cultural backgrounds. Four key features illustrate the uniqueness of Taiwanese perspectives: the idea of autonomy may not be conceptualized, prompt attention and choice of providers are on the same track, social support during care is trivially correlated to the total responsiveness score, and accountability of health providers is deemed essential to a health system.

  5. Autophagy as a macrophage response to bacterial infection.

    PubMed

    Gong, Lan; Devenish, Rodney J; Prescott, Mark

    2012-09-01

    The macrophage is a key component of host defense mechanisms against pathogens. In addition to the phagocytosis of bacteria and secretion of proinflammatory mediators by macrophages, autophagy, a process involved in turnover of cellular material, is a recently identified component of the immune response to bacterial infection. Despite the bactericidal effect of autophagy, some species of intracellular bacteria are able to survive by using one or more strategies to avoid host autophagic attack. Here, we review the latest findings on the interactions between bacteria and autophagy in macrophages. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

  6. Morphine Tolerance as a Function of Ratio Schedule: Response Requirement or Unit Price?

    ERIC Educational Resources Information Center

    Hughes, Christine; Sigmon, Stacey C.; Pitts, Raymond C.; Dykstra, Linda A.

    2005-01-01

    Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, "l"-methadone, and cocaine dose-dependently decreased…

  7. Changing Faculty Roles and Responsibilities: Expanding the Skill Set of Faculty Perspective "From a Graduate Dean"

    ERIC Educational Resources Information Center

    DePauw, Karen P.

    2003-01-01

    The roles and responsibilities of faculty in higher education continue to evolve. Although research and teaching have been perceived to be top priority, the skill set for faculty has expanded. Kennedy (1997) observed that academic freedom is widely shared value but that academic duty is mysterious. He identified the following as key components of…

  8. Military Review: Operation Desert Shield/Desert Storm

    DTIC Science & Technology

    1991-09-01

    areas of responsibility and ob- where he could best interact with key operation- jectives to influence the outcome of the battle. al wmmanders: the...Air component command- Key to successful operational command was er for air support, the Saudi Joint Forces Coin- the interaction of the two command...opterira~~ d-~ a~ ini ection as in available news people in the field. - Vtnmam.... The operational securiy/top safety prMAlem Dese ~amnind actio oereid

  9. Million Degree Plasmas in Extreme Ultraviolet (EUV) Astrophysics. White Paper in Response to Astro2010 Science Call

    DTIC Science & Technology

    2010-01-01

    photometry , timing measurements of suitable cadence, and advanced theory are the keys to understanding the physics of million degree plasmas in...Disentangling these components requires time - and phase- resolved spectroscopic observations of a sample that spans a range of mass accretion rates...many narrow lines, or a continuum with strong, broad absorption features. Key Objective: Obtaining time - and phase- resolved high-resolution EUV

  10. "Dateline NBC"'s Persuasive Attack on Wal-Mart.

    ERIC Educational Resources Information Center

    Benoit, William L.; Dorries, Bruce

    1996-01-01

    Develops a typology of persuasive attack strategies. Identifies two key components of persuasive attack: responsibility and offensiveness. Describes several strategies for intensifying each of these elements. Applies this analysis to "Dateline NBC"'s allegations that Wal-Mart's "Buy American" campaign was deceptive. Concludes…

  11. Can current moisture responses predict soil CO2 efflux under altered precipitation regimes? A synthesis of manipulation experiments

    Treesearch

    S. Vicca; M. Bahn; M. Estiarte; E. E. van Loon; R. Vargas; G. Alberti; P. Ambus; M. A. Arain; C. Beier; L. P. Bentley; W. Borken; N. Buchmann; S. L. Collins; G. de Dato; J. S. Dukes; C. Escolar; P. Fay; G. Guidolotti; P. J. Hanson; A. Kahmen; G. Kröel-Dulay; T. Ladreiter-Knauss; K. S. Larsen; E. Lellei-Kovacs; E. Lebrija-Trejos; F. T. Maestre; S. Marhan; M. Marshall; P. Meir; Y. Miao; J. Muhr; P. A. Niklaus; R. Ogaya; J. Peñuelas; C. Poll; L. E. Rustad; K. Savage; A. Schindlbacher; I. K. Schmidt; A. R. Smith; E. D. Sotta; V. Suseela; A. Tietema; N. van Gestel; O. van Straaten; S. Wan; U. Weber; I. A. Janssens

    2014-01-01

    As a key component of the carbon cycle, soil CO2 efflux (SCE) is being increasingly studied to improve our mechanistic understanding of this important carbon flux. Predicting ecosystem responses to climate change often depends an extrapolation of current relationships between ecosystem processes and their climatic drivers to conditions not yet experienced by the...

  12. Understory fern community structure, growth and spore production responses to a large-scale hurricane experiment in a Puerto Rico rainforest

    Treesearch

    Joanne M. Sharpe; Aaron B. Shiels

    2014-01-01

    Ferns are abundant in most rainforest understories yet their responses to hurricanes have not been well studied. Fern community structure, growth and spore production were monitored for two years before and five years after a large-scale experiment that simulated two key components of severe hurricane disturbance: canopy openness and debris deposition. The canopy was...

  13. Theoretical models for coronary vascular biomechanics: Progress & challenges

    PubMed Central

    Waters, Sarah L.; Alastruey, Jordi; Beard, Daniel A.; Bovendeerd, Peter H.M.; Davies, Peter F.; Jayaraman, Girija; Jensen, Oliver E.; Lee, Jack; Parker, Kim H.; Popel, Aleksander S.; Secomb, Timothy W.; Siebes, Maria; Sherwin, Spencer J.; Shipley, Rebecca J.; Smith, Nicolas P.; van de Vosse, Frans N.

    2013-01-01

    A key aim of the cardiac Physiome Project is to develop theoretical models to simulate the functional behaviour of the heart under physiological and pathophysiological conditions. Heart function is critically dependent on the delivery of an adequate blood supply to the myocardium via the coronary vasculature. Key to this critical function of the coronary vasculature is system dynamics that emerge via the interactions of the numerous constituent components at a range of spatial and temporal scales. Here, we focus on several components for which theoretical approaches can be applied, including vascular structure and mechanics, blood flow and mass transport, flow regulation, angiogenesis and vascular remodelling, and vascular cellular mechanics. For each component, we summarise the current state of the art in model development, and discuss areas requiring further research. We highlight the major challenges associated with integrating the component models to develop a computational tool that can ultimately be used to simulate the responses of the coronary vascular system to changing demands and to diseases and therapies. PMID:21040741

  14. Automated threat response recommendation in environments of high data uncertainty using the Countermeasure Association Technique (CMAT)

    NASA Astrophysics Data System (ADS)

    Chapman, George B.; Johnson, Glenn; Burdick, Robert

    1991-09-01

    The CounterMeasure Association Technique (CMAT) is discussed which was developed for the Air Force, and is used to automatically recommend countermeasure and maneuver response to a pilot while he is under missile attack. The overall system is discussed, as well as several key technical components. These components include use of fuzzy sets to specify data uncertainty, use of mimic nets to train the CMAT algorithm to make the same resource optimization tradeoffs as made in a data base of library of training scenarios, and use of several data compression techniques to store the countermeasure effectiveness data base.

  15. Links between the police response and women's psychological outcomes following intimate partner violence.

    PubMed

    Srinivas, Tejaswinhi; DePrince, Anne P

    2015-01-01

    Virtually no research considers the psychological impact of institutional support for survivors of intimate partner violence (IPV). This study sought to fill this gap by examining associations between one component of institutional support--the police response--and posttraumatic stress disorder (PTSD) symptom severity and posttrauma appraisals (i.e., anger, fear, and self-blame) in a diverse sample of female IPV survivors (N = 236). Results indicated that a more negative police response, as operationalized by women's unmet expectations in relation to the police, was significantly associated with greater PTSD symptom severity in a very conservative test that involved controlling for personal resources and social support. Police response was not significantly associated with the tested posttrauma appraisals. Implications for policy and practice will be discussed. This study advances understanding of the psychological impact of the police response--one key component of institutional support.

  16. A Bayesian Approach to Estimating Coupling Between Neural Components: Evaluation of the Multiple Component, Event-Related Potential (mcERP) Algorithm

    NASA Technical Reports Server (NTRS)

    Shah, Ankoor S.; Knuth, Kevin H.; Truccolo, Wilson A.; Ding, Ming-Zhou; Bressler, Steven L.; Schroeder, Charles E.; Clancy, Daniel (Technical Monitor)

    2002-01-01

    Accurate measurement of single-trial responses is key to a definitive use of complex electromagnetic and hemodynamic measurements in the investigation of brain dynamics. We developed the multiple component, Event-Related Potential (mcERP) approach to single-trial response estimation. To improve our resolution of dynamic interactions between neuronal ensembles located in different layers within a cortical region and/or in different cortical regions. The mcERP model assets that multiple components defined as stereotypic waveforms comprise the stimulus-evoked response and that these components may vary in amplitude and latency from trial to trial. Maximum a posteriori (MAP) solutions for the model are obtained by iterating a set of equations derived from the posterior probability. Our first goal was to use the ANTWERP algorithm to analyze interactions (specifically latency and amplitude correlation) between responses in different layers within a cortical region. Thus, we evaluated the model by applying the algorithm to synthetic data containing two correlated local components and one independent far-field component. Three cases were considered: the local components were correlated by an interaction in their single-trial amplitudes, by an interaction in their single-trial latencies, or by an interaction in both amplitude and latency. We then analyzed the accuracy with which the algorithm estimated the component waveshapes and the single-trial parameters as a function of the linearity of each of these relationships. Extensions of these analyses to real data are discussed as well as ongoing work to incorporate more detailed prior information.

  17. Evolving Tale of TCPs: New Paradigms and Old Lacunae

    PubMed Central

    Dhaka, Namrata; Bhardwaj, Vasudha; Sharma, Manoj K.; Sharma, Rita

    2017-01-01

    Teosinte Branched1/Cycloidea/Proliferating cell factors (TCP) genes are key mediators of genetic innovations underlying morphological novelties, stress adaptation, and evolution of immune response in plants. They have a remarkable ability to integrate and translate diverse endogenous, and environmental signals with high fidelity. Compilation of studies, aimed at elucidating the mechanism of TCP functions, shows that it takes an amalgamation and interplay of several different factors, regulatory processes and pathways, instead of individual components, to achieve the incredible functional diversity and specificity, demonstrated by TCP proteins. Through this minireview, we provide a brief description of key structural features and molecular components, known so far, that operate this conglomerate, and highlight the important conceptual challenges and lacunae in TCP research. PMID:28421104

  18. Evolving Tale of TCPs: New Paradigms and Old Lacunae.

    PubMed

    Dhaka, Namrata; Bhardwaj, Vasudha; Sharma, Manoj K; Sharma, Rita

    2017-01-01

    Teosinte Branched1/Cycloidea/Proliferating cell factors (TCP) genes are key mediators of genetic innovations underlying morphological novelties, stress adaptation, and evolution of immune response in plants. They have a remarkable ability to integrate and translate diverse endogenous, and environmental signals with high fidelity. Compilation of studies, aimed at elucidating the mechanism of TCP functions, shows that it takes an amalgamation and interplay of several different factors, regulatory processes and pathways, instead of individual components, to achieve the incredible functional diversity and specificity, demonstrated by TCP proteins. Through this minireview, we provide a brief description of key structural features and molecular components, known so far, that operate this conglomerate, and highlight the important conceptual challenges and lacunae in TCP research.

  19. Systematic mapping of two component response regulators to gene targets in a model sulfate reducing bacterium.

    PubMed

    Rajeev, Lara; Luning, Eric G; Dehal, Paramvir S; Price, Morgan N; Arkin, Adam P; Mukhopadhyay, Aindrila

    2011-10-12

    Two component regulatory systems are the primary form of signal transduction in bacteria. Although genomic binding sites have been determined for several eukaryotic and bacterial transcription factors, comprehensive identification of gene targets of two component response regulators remains challenging due to the lack of knowledge of the signals required for their activation. We focused our study on Desulfovibrio vulgaris Hildenborough, a sulfate reducing bacterium that encodes unusually diverse and largely uncharacterized two component signal transduction systems. We report the first systematic mapping of the genes regulated by all transcriptionally acting response regulators in a single bacterium. Our results enabled functional predictions for several response regulators and include key processes of carbon, nitrogen and energy metabolism, cell motility and biofilm formation, and responses to stresses such as nitrite, low potassium and phosphate starvation. Our study also led to the prediction of new genes and regulatory networks, which found corroboration in a compendium of transcriptome data available for D. vulgaris. For several regulators we predicted and experimentally verified the binding site motifs, most of which were discovered as part of this study. The gene targets identified for the response regulators allowed strong functional predictions to be made for the corresponding two component systems. By tracking the D. vulgaris regulators and their motifs outside the Desulfovibrio spp. we provide testable hypotheses regarding the functions of orthologous regulators in other organisms. The in vitro array based method optimized here is generally applicable for the study of such systems in all organisms.

  20. Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

    PubMed Central

    Pamenter, Matthew E.; Powell, Frank L.

    2016-01-01

    Ventilatory responses to hypoxia vary widely depending on the pattern and length of hypoxic exposure. Acute, prolonged, or intermittent hypoxic episodes can increase or decrease breathing for seconds to years, both during the hypoxic stimulus, and also after its removal. These myriad effects are the result of a complicated web of molecular interactions that underlie plasticity in the respiratory control reflex circuits and ultimately control the physiology of breathing in hypoxia. Since the time domains of the physiological hypoxic ventilatory response (HVR) were identified, considerable research effort has gone toward elucidating the underlying molecular mechanisms that mediate these varied responses. This research has begun to describe complicated and plastic interactions in the relay circuits between the peripheral chemoreceptors and the ventilatory control circuits within the central nervous system. Intriguingly, many of these molecular pathways seem to share key components between the different time domains, suggesting that varied physiological HVRs are the result of specific modifications to overlapping pathways. This review highlights what has been discovered regarding the cell and molecular level control of the time domains of the HVR, and highlights key areas where further research is required. Understanding the molecular control of ventilation in hypoxia has important implications for basic physiology and is emerging as an important component of several clinical fields. PMID:27347896

  1. Team Training and Institutional Protocols to Prevent Shoulder Dystocia Complications.

    PubMed

    Smith, Samuel

    2016-12-01

    Shoulder dystocia is an obstetrical emergency that may result in significant neonatal complications. It requires rapid recognition and a coordinated response. Standardization of care, teamwork and communication, and clinical simulation are the key components of patient safety programs in obstetrics. Simulation-based team training and institutional protocols for the management of shoulder dystocia are emerging as integral components of many labor and delivery safety initiatives because of their impact on technical skills and team performance.

  2. Improvement in visual search with practice: mapping learning-related changes in neurocognitive stages of processing.

    PubMed

    Clark, Kait; Appelbaum, L Gregory; van den Berg, Berry; Mitroff, Stephen R; Woldorff, Marty G

    2015-04-01

    Practice can improve performance on visual search tasks; the neural mechanisms underlying such improvements, however, are not clear. Response time typically shortens with practice, but which components of the stimulus-response processing chain facilitate this behavioral change? Improved search performance could result from enhancements in various cognitive processing stages, including (1) sensory processing, (2) attentional allocation, (3) target discrimination, (4) motor-response preparation, and/or (5) response execution. We measured event-related potentials (ERPs) as human participants completed a five-day visual-search protocol in which they reported the orientation of a color popout target within an array of ellipses. We assessed changes in behavioral performance and in ERP components associated with various stages of processing. After practice, response time decreased in all participants (while accuracy remained consistent), and electrophysiological measures revealed modulation of several ERP components. First, amplitudes of the early sensory-evoked N1 component at 150 ms increased bilaterally, indicating enhanced visual sensory processing of the array. Second, the negative-polarity posterior-contralateral component (N2pc, 170-250 ms) was earlier and larger, demonstrating enhanced attentional orienting. Third, the amplitude of the sustained posterior contralateral negativity component (SPCN, 300-400 ms) decreased, indicating facilitated target discrimination. Finally, faster motor-response preparation and execution were observed after practice, as indicated by latency changes in both the stimulus-locked and response-locked lateralized readiness potentials (LRPs). These electrophysiological results delineate the functional plasticity in key mechanisms underlying visual search with high temporal resolution and illustrate how practice influences various cognitive and neural processing stages leading to enhanced behavioral performance. Copyright © 2015 the authors 0270-6474/15/355351-09$15.00/0.

  3. Word-to-picture recognition is a function of motor components mappings at the stage of retrieval.

    PubMed

    Brouillet, Denis; Brouillet, Thibaut; Milhau, Audrey; Heurley, Loïc; Vagnot, Caroline; Brunel, Lionel

    2016-10-01

    Embodied approaches of cognition argue that retrieval involves the re-enactment of both sensory and motor components of the desired remembering. In this study, we investigated the effect of motor action performed to produce the response in a recognition task when this action is compatible with the affordance of the objects that have to be recognised. In our experiment, participants were first asked to learn a list of words referring to graspable objects, and then told to make recognition judgements on pictures. The pictures represented objects where the graspable part was either pointing to the same or to the opposite side of the "Yes" response key. Results show a robust effect of compatibility between objects affordance and response hand. Moreover, this compatibility improves participants' ability of discrimination, suggesting that motor components are relevant cue for memory judgement at the stage of retrieval in a recognition task. More broadly, our data highlight that memory judgements are a function of motor components mappings at the stage of retrieval. © 2015 International Union of Psychological Science.

  4. Glycomaterials for probing host–pathogen interactions and the immune response

    PubMed Central

    Huang, Mia L; Fisher, Christopher J

    2016-01-01

    The initial engagement of host cells by pathogens is often mediated by glycan structures presented on the cell surface. Various components of the glycocalyx can be targeted by pathogens for adhesion to facilitate infection. Glycans also play integral roles in the modulation of the host immune response to infection. Therefore, understanding the parameters that define glycan interactions with both pathogens and the various components of the host immune system can aid in the development of strategies to prevent, interrupt, or manage infection. Glycomaterials provide a unique and powerful tool with which to interrogate the compositional and functional complexity of the glycocalyx. The objective of this review is to highlight some key contributions from this area of research in deciphering the mechanisms of pathogenesis and the associated host response. PMID:27190259

  5. Flexion Reflex Can Interrupt and Reset the Swimming Rhythm.

    PubMed

    Elson, Matthew S; Berkowitz, Ari

    2016-03-02

    The spinal cord can generate the hip flexor nerve activity underlying leg withdrawal (flexion reflex) and the rhythmic, alternating hip flexor and extensor activities underlying locomotion and scratching, even in the absence of brain inputs and movement-related sensory feedback. It has been hypothesized that a common set of spinal interneurons mediates flexion reflex and the flexion components of locomotion and scratching. Leg cutaneous stimuli that evoke flexion reflex can alter the timing of (i.e., reset) cat walking and turtle scratching rhythms; in addition, reflex responses to leg cutaneous stimuli can be modified during cat and human walking and turtle scratching. Both of these effects depend on the phase (flexion or extension) of the rhythm in which the stimuli occur. However, similar interactions between leg flexion reflex and swimming have not been reported. We show here that a tap to the foot interrupted and reset the rhythm of forward swimming in spinal, immobilized turtles if the tap occurred during the swim hip extensor phase. In addition, the hip flexor nerve response to an electrical foot stimulus was reduced or eliminated during the swim hip extensor phase. These two phase-dependent effects of flexion reflex on the swim rhythm and vice versa together demonstrate that the flexion reflex spinal circuit shares key components with or has strong interactions with the swimming spinal network, as has been shown previously for cat walking and turtle scratching. Therefore, leg flexion reflex circuits likely share key spinal interneurons with locomotion and scratching networks across limbed vertebrates generally. The spinal cord can generate leg withdrawal (flexion reflex), locomotion, and scratching in limbed vertebrates. It has been hypothesized that there is a common set of spinal cord neurons that produce hip flexion during flexion reflex, locomotion, and scratching based on evidence from studies of cat and human walking and turtle scratching. We show here that flexion reflex and swimming also share key spinal cord components based on evidence from turtles. Foot stimulation can reset the timing of the swimming rhythm and the response to each foot stimulation can itself be altered by the swim rhythm. Collectively, these studies suggest that spinal cord neuronal networks underlying flexion reflex, multiple forms of locomotion, and scratching share key components. Copyright © 2016 the authors 0270-6474/16/362819-08$15.00/0.

  6. Effect Anticipation Affects Perceptual, Cognitive, and Motor Phases of Response Preparation: Evidence from an Event-Related Potential (ERP) Study

    PubMed Central

    Harrison, Neil R.; Ziessler, Michael

    2016-01-01

    The anticipation of action effects is a basic process that can be observed even for key-pressing responses in a stimulus-response paradigm. In Ziessler et al.’s (2012) experiments participants first learned arbitrary effects of key-pressing responses. In the test phase an imperative stimulus determined the response, but participants withheld the response until a Go-stimulus appeared. Reaction times (RTs) were shorter if the Go-stimulus was compatible with the learned response effect. This is strong evidence that effect representations were activated during response planning. Here, we repeated the experiment using event-related potentials (ERPs), and we found that Go-stimulus locked ERPs depended on the compatibility relationship between the Go-stimulus and the response effect. In general, this supports the interpretation of the behavioral data. More specifically, differences in the ERPs between compatible and incompatible Go-stimuli were found for the early perceptual P1 component and the later frontal P2 component. P1 differences were found only in the second half of the experiment and for long stimulus onset asynchronies (SOAs) between imperative stimulus and Go-stimulus, i.e., when the effect was fully anticipated and the perceptual system was prepared for the effect-compatible Go-stimulus. P2 amplitudes, likely associated with evaluation and conflict detection, were larger when Go-stimulus and effect were incompatible; presumably, incompatibility increased the difficulty of effect anticipation. Onset of response-locked lateralized readiness potentials (R-LRPs) occurred earlier under incompatible conditions indicating extended motor processing. Together, these results strongly suggest that effect anticipation affects all (i.e., perceptual, cognitive, and motor) phases of response preparation. PMID:26858621

  7. Effect Anticipation Affects Perceptual, Cognitive, and Motor Phases of Response Preparation: Evidence from an Event-Related Potential (ERP) Study.

    PubMed

    Harrison, Neil R; Ziessler, Michael

    2016-01-01

    The anticipation of action effects is a basic process that can be observed even for key-pressing responses in a stimulus-response paradigm. In Ziessler et al.'s (2012) experiments participants first learned arbitrary effects of key-pressing responses. In the test phase an imperative stimulus determined the response, but participants withheld the response until a Go-stimulus appeared. Reaction times (RTs) were shorter if the Go-stimulus was compatible with the learned response effect. This is strong evidence that effect representations were activated during response planning. Here, we repeated the experiment using event-related potentials (ERPs), and we found that Go-stimulus locked ERPs depended on the compatibility relationship between the Go-stimulus and the response effect. In general, this supports the interpretation of the behavioral data. More specifically, differences in the ERPs between compatible and incompatible Go-stimuli were found for the early perceptual P1 component and the later frontal P2 component. P1 differences were found only in the second half of the experiment and for long stimulus onset asynchronies (SOAs) between imperative stimulus and Go-stimulus, i.e., when the effect was fully anticipated and the perceptual system was prepared for the effect-compatible Go-stimulus. P2 amplitudes, likely associated with evaluation and conflict detection, were larger when Go-stimulus and effect were incompatible; presumably, incompatibility increased the difficulty of effect anticipation. Onset of response-locked lateralized readiness potentials (R-LRPs) occurred earlier under incompatible conditions indicating extended motor processing. Together, these results strongly suggest that effect anticipation affects all (i.e., perceptual, cognitive, and motor) phases of response preparation.

  8. Mothers' amygdala response to positive or negative infant affect is modulated by personal relevance

    USDA-ARS?s Scientific Manuscript database

    Understanding, prioritizing and responding to infant affective cues is a key component of motherhood, with long-term implications for infant socio-emotional development. This important task includes identifying unique characteristics of one's own infant, as they relate to differences in affect valen...

  9. Chapter 7 - Mapping potential vegetation type for the LANDFIRE Prototype Project

    Treesearch

    Tracey S. Frescino; Matthew G. Rollins

    2006-01-01

    Mapped potential vegetation functioned as a key component in the Landscape Fire and Resource Management Planning Tools Prototype Project (LANDFIRE Prototype Project). Disturbance regimes, vegetation response and succession, and wildland fuel dynamics across landscapes are controlled by patterns of the environmental factors (biophysical settings) that entrain the...

  10. Effective Communication: A Key to Successful Collaboration.

    ERIC Educational Resources Information Center

    Price, Joseph P.

    1991-01-01

    This paper points out the importance of special educators' communication skills in effective collaboration. The basic components of face-to-face communication are discussed, emphasizing the role of the speaker and listener. An explanation of the process of active listening is also included, noting possible verbal and nonverbal listener responses.…

  11. School Psychology Services: Community-Based, First-Order Crisis Intervention during the Gulf War.

    ERIC Educational Resources Information Center

    Klingman, Avigdor

    1992-01-01

    Examines the community-based mental health preventive measures undertaken by the school psychology services in response to the missile attacks on Israel during the Gulf War. Attempts to report and delineate the major assumptions and components of some of the key interventions. (Author/NB)

  12. Evaluating measures to assess soil health in long-term agroecosystem trials

    USDA-ARS?s Scientific Manuscript database

    Monitoring and assessing soil health is an important component of any land management system with a vision of sustaining soil resources. Soil organic matter(SOM)characteristics are key to soil health and responsive to tillage regime and crop management. As metrics of soil health, we evaluated surfac...

  13. The Role of International Research Collaboration in Enhancing Global Presence of an Institution

    ERIC Educational Resources Information Center

    Ao, Fiona Ka Wa

    2012-01-01

    In recent decades, higher education institutions have steadily increased their international involvement in response to globalization. High-level research is generally a key component in efforts to increase international visibility (Armstrong, 2007). International research collaborations are perceived to be an important way to enhance global…

  14. Genome-wide Association Analysis of Kernel Weight in Hard Winter Wheat

    USDA-ARS?s Scientific Manuscript database

    Wheat kernel weight is an important and heritable component of wheat grain yield and a key predictor of flour extraction. Genome-wide association analysis was conducted to identify genomic regions associated with kernel weight and kernel weight environmental response in 8 trials of 299 hard winter ...

  15. EVALUATION OF THE IMPLEMENTATION OF OPERATIONS AND MAINTENANCE PROGRAMS IN NEW JERSEY SCHOOLS

    EPA Science Inventory

    The Asbestos Hazard Emergency Response Act (AHERA) required all schools to develop and implement an asbestos management plan (AMP). The key component of the AMP is the operations and maintenance (O&M) program. A study was conducted to evaluate the implementation of O&M programs a...

  16. QTL and drought effects on leaf physiology in lowland Panicum virgatum

    USDA-ARS?s Scientific Manuscript database

    Switchgrass is a key component of plans to develop sustainable cellulosic ethanol production for bioenergy in the U.S. We sought quantitative trait loci (QTL) for leaf structure and function, and tested for genotype × environment interactions in response to drought using the Albany full-sib mapping...

  17. Optimizing the management of depression: primary care experience.

    PubMed

    Cameron, Catherine; Habert, Jeff; Anand, Leena; Furtado, Melissa

    2014-12-01

    This article is intended to identify some of the most important challenges faced by family physicians when treating MDD and to provide practical solutions. Key issues, reviewed from a primary care view point will include: treating to remission (and not just response), identification of high-risk groups, diagnosis, acute treatment approaches (including pharmacotherapy and the management of related side effects), the use of psychotherapy and somatic therapies, assessment of the adequacy of treatment including the assessment of remission, response measurement, optimal follow-up care throughout the phase of treatment, the key components of patient education and strategies for partial/limited response to the first-line antidepressant (switching, augmentation and combination strategies), how to provide support for improved treatment adherence, and approaches to prevent the recurrence of depressive episodes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Systematic mapping of two component response regulators to gene targets in a model sulfate reducing bacterium

    PubMed Central

    2011-01-01

    Background Two component regulatory systems are the primary form of signal transduction in bacteria. Although genomic binding sites have been determined for several eukaryotic and bacterial transcription factors, comprehensive identification of gene targets of two component response regulators remains challenging due to the lack of knowledge of the signals required for their activation. We focused our study on Desulfovibrio vulgaris Hildenborough, a sulfate reducing bacterium that encodes unusually diverse and largely uncharacterized two component signal transduction systems. Results We report the first systematic mapping of the genes regulated by all transcriptionally acting response regulators in a single bacterium. Our results enabled functional predictions for several response regulators and include key processes of carbon, nitrogen and energy metabolism, cell motility and biofilm formation, and responses to stresses such as nitrite, low potassium and phosphate starvation. Our study also led to the prediction of new genes and regulatory networks, which found corroboration in a compendium of transcriptome data available for D. vulgaris. For several regulators we predicted and experimentally verified the binding site motifs, most of which were discovered as part of this study. Conclusions The gene targets identified for the response regulators allowed strong functional predictions to be made for the corresponding two component systems. By tracking the D. vulgaris regulators and their motifs outside the Desulfovibrio spp. we provide testable hypotheses regarding the functions of orthologous regulators in other organisms. The in vitro array based method optimized here is generally applicable for the study of such systems in all organisms. PMID:21992415

  19. Contrast and autoshaping in multiple schedules varying reinforcer rate and duration.

    PubMed

    Hamilton, B E; Silberberg, A

    1978-07-01

    Thirteen master pigeons were exposed to multiple schedules in which reinforcement frequency (Experiment I) or duration (Experiment II) was varied. In Phases 1 and 3 of Experiment I, the values of the first and second components' random-interval schedules were 33 and 99 seconds, respectively. In Phase 2, these values were 99 seconds for both components. In Experiment II, a random-interval 33-second schedule was associated with each component. During Phases 1 and 3, the first and second components had hopper durations of 7.5 and 2.5 seconds respectively. During Phase 2, both components' hopper durations were 2.5 seconds. In each experiment, positive contrast obtained for about half the master subjects. The rest showed a rate increase in both components (positive induction). Each master subject's key colors and reinforcers were synchronously presented on a response-independent basis to a yoked control. Richer component key-pecking occurred during each experiment's Phases 1 and 3 among half these subjects. However, none responded during the contrast condition (unchanged component of each experiment's Phase 2). From this it is inferred that autoshaping did not contribute to the contrast and induction findings among master birds. Little evidence of local contrast (highest rate at beginning of richer component) was found in any subject. These data show that (a) contrast can occur independently from autoshaping, (b) contrast assays during equal-valued components may produce induction, (c) local contrast in multiple schedules often does not occur, and (d) differential hopper durations can produce autoshaping and contrast.

  20. Component-based target recognition inspired by human vision

    NASA Astrophysics Data System (ADS)

    Zheng, Yufeng; Agyepong, Kwabena

    2009-05-01

    In contrast with machine vision, human can recognize an object from complex background with great flexibility. For example, given the task of finding and circling all cars (no further information) in a picture, you may build a virtual image in mind from the task (or target) description before looking at the picture. Specifically, the virtual car image may be composed of the key components such as driver cabin and wheels. In this paper, we propose a component-based target recognition method by simulating the human recognition process. The component templates (equivalent to the virtual image in mind) of the target (car) are manually decomposed from the target feature image. Meanwhile, the edges of the testing image can be extracted by using a difference of Gaussian (DOG) model that simulates the spatiotemporal response in visual process. A phase correlation matching algorithm is then applied to match the templates with the testing edge image. If all key component templates are matched with the examining object, then this object is recognized as the target. Besides the recognition accuracy, we will also investigate if this method works with part targets (half cars). In our experiments, several natural pictures taken on streets were used to test the proposed method. The preliminary results show that the component-based recognition method is very promising.

  1. Regulation of the Expression of Bacterial Multidrug Exporters by Two-Component Signal Transduction Systems.

    PubMed

    Nishino, Kunihiko

    2018-01-01

    Bacterial multidrug exporters confer resistance to a wide range of antibiotics, dyes, and biocides. Recent studies have shown that there are many multidrug exporters encoded in bacterial genome. For example, it was experimentally identified that E. coli has at least 20 multidrug exporters. Because many of these multidrug exporters have overlapping substrate spectra, it is intriguing that bacteria, with their economically organized genomes, harbor such large sets of multidrug exporter genes. The key to understanding how bacteria utilize these multiple exporters lies in the regulation of exporter expression. Bacteria have developed signaling systems for eliciting a variety of adaptive responses to their environments. These adaptive responses are often mediated by two-component regulatory systems. In this chapter, the method to identify response regulators that affect expression of multidrug exporters is described.

  2. Toward Understanding Trust: A Response to Adams and Miskell

    ERIC Educational Resources Information Center

    Romero, Lisa S.; Mitchell, Douglas E.

    2018-01-01

    Purpose: Trust is a key component of successful schools. Although scholars widely agree that trust is multifaceted, there is less agreement about the number and nature of these factors. In the October 2016 issue of "Educational Administration Quarterly," C. M. Adams and Miskell (see EJ1112413) argued that their Teacher Trust of District…

  3. A novel framework for interpretation of data from the fish short-term reproduction assay (FSTRA) for the detection of endocrined-disrupting chemicals

    EPA Science Inventory

    The fish short term reproduction assay (FSTRA) is a key component of the USEPA endocrine disruptor screening program (EDSP). The FSTRA considers several mechanistic and apical responses in fathead minnows (Pimephales promelas) to determine whether an unknown chemical is likely to...

  4. A novel framework for interpretation of data from the fish short-term reproduction assay (FSTRA) for the detection of endocrine-disrupting chemicals

    EPA Science Inventory

    The fish short term reproduction assay (FSTRA) is a key component of the USEPA endocrine disruptor screening program (EDSP). The FSTRA considers several mechanistic and apical responses in fathead minnows (Pimephales promelas) to determine whether an unknown chemical is likely t...

  5. Fostering Scientific Literacy and Critical Thinking in Elementary Science Education

    ERIC Educational Resources Information Center

    Vieira, Rui Marques; Tenreiro-Vieira, Celina

    2016-01-01

    Scientific literacy (SL) and critical thinking (CT) are key components of science education aiming to prepare students to think and to function as responsible citizens in a world increasingly affected by science and technology (S&T). Therefore, students should be given opportunities in their science classes to be engaged in learning…

  6. Life Skills-Based HIV Education: Some Virtues and Errors

    ERIC Educational Resources Information Center

    Clarke, David; Yankah, Ekua; Aggleton, Peter

    2015-01-01

    Since the early 1990s, life skills education has benefitted substantially from international agency advocacy and support, linked to its implementation in several countries as a key component of the education sector response to sexual health and HIV. The concept of life skills was first promoted by the World Health Organization through its…

  7. Single Event Effects (SEE) for Power Metal-Oxide-Semiconductor Field-Effect Transistors (MOSFETs)

    NASA Technical Reports Server (NTRS)

    Lauenstein, Jean-Marie

    2011-01-01

    Single-event gate rupture (SEGR) continues to be a key failure mode in power MOSFETs. (1) SEGR is complex, making rate prediction difficult SEGR mechanism has two main components: (1) Oxide damage-- Reduces field required for rupture (2) Epilayer response -- Creates transient high field across the oxide.

  8. First Steps to School Readiness: South Carolina's Response to At-Risk Early Childhood Population.

    ERIC Educational Resources Information Center

    Buford, Rhonda; Stegelin, Dolores A.

    2003-01-01

    Describes South Carolina's new state early childhood program, First Steps to School Readiness. Includes a profile of the state's at-risk child population, noting poverty and education risk indicators, and describing key program components. The article discusses program oversight, local program partnerships, program funding mechanisms, and local…

  9. Coordination between veterinary services and other relevant authorities: a key component of good public governance.

    PubMed

    Bellemain, V

    2012-08-01

    Coordination between Veterinary Services and other relevant authorities is a key component of good public governance, especially for effective action and optimal management of available resources. The importance of good coordination is reflected in the World Organisation for Animal Health'Tool forthe Evaluation of Performance of Veterinary Services', which includes a critical competency on coordination. Many partners from technical, administrative and legal fields are involved. The degree of formalisation of coordination tends to depend on a country's level of organisation and development. Contingency plans against avian influenza led to breakthroughs in many countries in the mid-2000s. While interpersonal relationships remain vital, not everything should hinge on them. Organisation and management are critical to operational efficiency. The distribution of responsibilities needs to be defined clearly, avoiding duplication and areas of conflict. Lead authorities should be designated according to subject (Veterinary Services in animal health areas) and endowed with the necessary legitimacy. Lead authorities will be responsible for coordinating the drafting and updating of the relevant documents: agreements between authorities, contingency plans, standard operating procedures, etc.

  10. Separating spatial search and efficiency rates as components of predation risk

    PubMed Central

    DeCesare, Nicholas J.

    2012-01-01

    Predation risk is an important driver of ecosystems, and local spatial variation in risk can have population-level consequences by affecting multiple components of the predation process. I use resource selection and proportional hazard time-to-event modelling to assess the spatial drivers of two key components of risk—the search rate (i.e. aggregative response) and predation efficiency rate (i.e. functional response)—imposed by wolves (Canis lupus) in a multi-prey system. In my study area, both components of risk increased according to topographic variation, but anthropogenic features affected only the search rate. Predicted models of the cumulative hazard, or risk of a kill, underlying wolf search paths validated well with broad-scale variation in kill rates, suggesting that spatial hazard models provide a means of scaling up from local heterogeneity in predation risk to population-level dynamics in predator–prey systems. Additionally, I estimated an integrated model of relative spatial predation risk as the product of the search and efficiency rates, combining the distinct contributions of spatial heterogeneity to each component of risk. PMID:22977145

  11. Educational Destruction and Reconstruction in Disrupted Societies. Final Report and Case Studies of the Workshop Held on 15-16 May 1997, Geneva, Switzerland, Organized Jointly by the International Bureau of Education and the University of Geneva.

    ERIC Educational Resources Information Center

    Tawil, Sobhi, Ed.

    This volume addresses the dual problems of providing rapid educational responses in global conflict and crisis situations and assessing the role of education in the root causes of these conflicts. Education and training are key components of international relief responses to emergencies resulting from conflicts. Even more important, rehabilitation…

  12. Designing and implementing an electronic dashboard for disease outbreaks response - Case study of the 2013-2014 Somalia Polio outbreak response dashboard

    PubMed Central

    Kamadjeu, Raoul; Gathenji, Caroline

    2017-01-01

    In April 2013, a case of wild polio virus (WPV) was detected in the Somalia capital Mogadishu. This inaugurated what is now referred to as the 2013-2014 Horn of Africa Polio outbreak with cases reported in Somalia, Kenya and Ethiopia. By the notification of the last polio case in August 2014, 223 cases of WPV had been reported in Somalia, Kenya and Ethiopia of which 199 in Somalia alone. The outbreak response required timely exchange of information between the outbreak response coordination unit (in Nairobi) and local staff located in multiple locations inside the country. The need to track and timely respond to information requests, to satisfy the information/data needs of polio partners and to track key outbreak response performance indicators dictated the need to urgently set up an online dashboard. The Somalia Polio Room dashboard provided a graphical display of the polio outbreak data to track progress and inform decision making. The system was designed using free and open sources components and seamlessly integrated existing polio surveillance data for real time monitoring of key outbreak response performance indicators. In this article, we describe the design and operation of an electronic dashboard for disease surveillance in an outbreak situation and used the lessons learned to propose key design considerations and functional requirements for online electronic dashboards for disease outbreak response. PMID:29296157

  13. Designing and implementing an electronic dashboard for disease outbreaks response - Case study of the 2013-2014 Somalia Polio outbreak response dashboard.

    PubMed

    Kamadjeu, Raoul; Gathenji, Caroline

    2017-01-01

    In April 2013, a case of wild polio virus (WPV) was detected in the Somalia capital Mogadishu. This inaugurated what is now referred to as the 2013-2014 Horn of Africa Polio outbreak with cases reported in Somalia, Kenya and Ethiopia. By the notification of the last polio case in August 2014, 223 cases of WPV had been reported in Somalia, Kenya and Ethiopia of which 199 in Somalia alone. The outbreak response required timely exchange of information between the outbreak response coordination unit (in Nairobi) and local staff located in multiple locations inside the country. The need to track and timely respond to information requests, to satisfy the information/data needs of polio partners and to track key outbreak response performance indicators dictated the need to urgently set up an online dashboard. The Somalia Polio Room dashboard provided a graphical display of the polio outbreak data to track progress and inform decision making. The system was designed using free and open sources components and seamlessly integrated existing polio surveillance data for real time monitoring of key outbreak response performance indicators. In this article, we describe the design and operation of an electronic dashboard for disease surveillance in an outbreak situation and used the lessons learned to propose key design considerations and functional requirements for online electronic dashboards for disease outbreak response.

  14. Synthesis of Natural Electric and Magnetic Time Series Using Impulse Responses of Inter-station Transfer Functions and a Reference

    NASA Astrophysics Data System (ADS)

    Wang, H.; Cheng, J.

    2017-12-01

    A method to Synthesis natural electric and magnetic Time series is proposed whereby the time series of local site are derived using an Impulse Response and a reference (STIR). The method is based on the assumption that the external source of magnetic fields are uniform, and the electric and magnetic fields acquired at the surface satisfy a time-independent linear relation in frequency domain.According to the convolution theorem, we can synthesize natural electric and magnetic time series using the impulse responses of inter-station transfer functions with a reference. Applying this method, two impulse responses need to be estimated: the quasi-MT impulse response tensor and the horizontal magnetic impulse response tensor. These impulse response tensors relate the local horizontal electric and magnetic components with the horizontal magnetic components at a reference site, respectively. Some clean segments of times series are selected to estimate impulse responses by using least-square (LS) method. STIR is similar with STIN (Wang, 2017), but STIR does not need to estimate the inter-station transfer functions, and the synthesized data are more accurate in high frequency, where STIN fails when the inter-station transfer functions are contaminated severely. A test with good quality of MT data shows that synthetic time-series are similar to natural electric and magnetic time series. For contaminated AMT example, when this method is used to remove noise present at the local site, the scatter of MT sounding curves are clear reduced, and the data quality are improved. *This work is funded by National Key R&D Program of China(2017YFC0804105),National Natural Science Foundation of China (41604064, 51574250), State Key Laboratory of Coal Resources and Safe Mining ,China University of Mining & Technology,(SKLCRSM16DC09)

  15. Isolation and purification of antigenic components of Cryptococcus.

    PubMed

    Wozniak, Karen L; Levitz, Stuart M

    2009-01-01

    The encapsulated fungal pathogens Cryptococcus neoformans and Cryptococcus gattii are significant agents of life-threatening infections, particularly in persons with suppressed cell-mediated immunity. This chapter provides detailed methodology for the purification of two of the major antigen fractions of C. neoformans: glucuronoxylomannan (GXM) and mannoprotein (MP). GXM is the primary component of the polysaccharide capsule, which is the major cryptococcal virulence factor. In contrast, MPs have been identified as key antigens that stimulate T-cell responses. Purification of GXM and MP should assist investigators studying the antigenic, biochemical, and virulence properties of Cryptococcus species.

  16. Planning for the future.

    PubMed

    Stiewing, Janis

    2002-01-01

    Revising the strategic plan was the beginning of a multiyear initiative that will determine the path of the JRCERT. The key word in the preceding statement is beginning. The strategic plan is an ever-changing document. Although some components, such as the values statements, will stand over time, other components will change as accreditation and educational arenas change. That is the paradox of strategic planning: Remaining true to the vision, values and mission statements requires knowing when to change to keep the JRCERT aligned with the responsive to its communities of interest.

  17. Rapidly-progressive catatonia responsive to zolpidem in a patient with ovarian teratoma-associated paraneoplastic encephalitis.

    PubMed

    Amorim, Edilberto; McDade, Eric M

    2016-08-01

    Psychiatric symptoms and catatonia are key components of the clinical presentation of paraneoplastic encephalitis; additionally symptoms can be long-lasting and often difficult to treat. We report a 73-year-old patient with rapidly progressive catatonia not responsive to immunotherapy, tumor resection, electroconvulsive therapy, or benzodiazepines who had significant improvement after zolpidem administration. This report suggests that zolpidem is an option in the treatment of patients with refractory catatonia and paraneoplastic encephalitis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. A novel framework for interpretation of data from the fish short-term reproduction assay (FSTRA) for the detection of endocrine-disrupting chemicals (poster)

    EPA Science Inventory

    The fish short term reproduction assay (FSTRA) is a key component of the USEPA endocrine disruptor screening program (EDSP). The FSTRA considers several mechanistic and apical responses in fathead minnows (Pimephales promelas) to determine whether an unknown chemical is likely to...

  19. Can current moisture responses predict soil CO2 efflux under altered precipitation regimes? A synthesis of manipulation experiments

    USDA-ARS?s Scientific Manuscript database

    As a key component of the carbon cycle, soil respiration (Rsoil) is being excessively studied with the aim of improving our understanding as well as our ability to predict Rsoil when climate changes. Many manipulation experiments have been performed to test how Rsoil and other carbon fluxes and ecos...

  20. Global change in forests: responses of species, communities, and biomes

    Treesearch

    Andrew J. Hansen; Ronald P. Neilson; Virginia H. Dale; Curtis H. Flather; Louis R. Iverson; David J. Currie; Sarah Shafer; Rosamonde Cook; Partick J. Bartlein

    2001-01-01

    This article serves as a primer on forest biodiversity as a key component of global change. We first synthesize current knowledge of interactions among climate, land use, and biodiversity. We then summarize the results of new analyses on the potential effects of human-induced climate change on forest biodiversity. Our models project how possible future climates may...

  1. Supervisors' On-Script Feedback Comments on Drafts of Dissertations: Socialising Students into the Academic Discourse Community

    ERIC Educational Resources Information Center

    Basturkmen, Helen; East, Martin; Bitchener, John

    2014-01-01

    Supervising masters and doctoral dissertations is a key function of teaching in higher education and giving written feedback on draft sections is an essential component of this function. However, the specific types of response that supervisors give to their dissertation students' written work have received limited research interest to date. The…

  2. The Great Balancing Act: Financial Equity and Local Control. Can Vermont's Act 60 Do It?

    ERIC Educational Resources Information Center

    Jimerson, Lorna

    Vermont's Equal Educational Opportunity Act of 1997 (Act 60) has attracted attention because of its funding and quality components, and the highly publicized responses to its implementation. A key feature is its "recapture" provision in which property-wealthy towns contribute to a state educational fund that helps support education in…

  3. Dance History Matters in British Higher Education

    ERIC Educational Resources Information Center

    Carter, Alexandra

    2007-01-01

    In response to concerns about the place and nature of dance history in British higher education curricula, a database was compiled of representative but significant examples of modules which focused directly on the teaching and learning of history, or had history as a key component. An analysis is presented of these modules in terms of the place…

  4. Fire effects on water quality: a synthesis of response regulating factors among contrasting ecosystems

    Treesearch

    Katherine J. Elliott; James M. Vose

    2006-01-01

    The key components of watershed processes are inputs in precipitation, interactions of vegetation, soil and water including evapotranspiration (water yield), overland flow (erosion), and storage and filtering (nutrients), and outputs in streamflow. Fire effects occur at the vegetation-soil interface and can result in altering overland flow and infiltration rate of...

  5. State-of-the-Science Workshop Report: Issues and Approaches in Low Dose–Response Extrapolation for Environmental Health Risk Assessment

    EPA Science Inventory

    Low-dose extrapolation model selection for evaluating the health effects of environmental pollutants is a key component of the risk assessment process. At a workshop held in Baltimore, MD, on April 23-24, 2007, and sponsored by U.S. Environmental Protection Agency (EPA) and Johns...

  6. Substrate-induced respiration in Puerto Rican soils: minimum glucose amendment

    Treesearch

    Marcela Zalamea; Grizelle Gonzalez

    2007-01-01

    Soil microbiota –usually quantified as microbial biomass –is a key component of terrestrial ecosystems, regulating nutrient cycling and organic matter turnover. Among the several methods developed for estimating soil microbial biomass, Substrate-Induced Respiration (SIR) is considered reliable and easy to implement; once the maximum respiratory response is determined...

  7. Rethinking Leadership Learning in Postgraduate Public Management Programmes

    ERIC Educational Resources Information Center

    Briggs, Ian; Raine, John

    2013-01-01

    Leadership forms a key component of the curriculum of most Master of Public Administration and other public management programmes, usually doing so on the basis of assumptions that leadership is (a) both a subject and a responsibility that all such students might expect to embrace in the course of their careers; and (b) in some respects at least,…

  8. Evaluating the Mechanism of Oxalate Synthesis of Fibroporia Radiculosa Isolates Adapting to Copper-Tolerance

    Treesearch

    Katie Marie Jenkins

    2012-01-01

    Despite the drawbacks associated with tolerant organisms, copper is still used as the key component in current wood preservatives. Copper-tolerant fungi, like Fibroporia radiculosa, produce and accumulate high levels of oxalate in response to copper. The biosynthesis of oxalate has been connected to specific enzymes in the glyoxylate and...

  9. Contrast and autoshaping in multiple schedules varying reinforcer rate and duration

    PubMed Central

    Hamilton, Bruce E.; Silberberg, Alan

    1978-01-01

    Thirteen master pigeons were exposed to multiple schedules in which reinforcement frequency (Experiment I) or duration (Experiment II) was varied. In Phases 1 and 3 of Experiment I, the values of the first and second components' random-interval schedules were 33 and 99 seconds, respectively. In Phase 2, these values were 99 seconds for both components. In Experiment II, a random-interval 33-second schedule was associated with each component. During Phases 1 and 3, the first and second components had hopper durations of 7.5 and 2.5 seconds respectively. During Phase 2, both components' hopper durations were 2.5 seconds. In each experiment, positive contrast obtained for about half the master subjects. The rest showed a rate increase in both components (positive induction). Each master subject's key colors and reinforcers were synchronously presented on a response-independent basis to a yoked control. Richer component key-pecking occurred during each experiment's Phases 1 and 3 among half these subjects. However, none responded during the contrast condition (unchanged component of each experiment's Phase 2). From this it is inferred that autoshaping did not contribute to the contrast and induction findings among master birds. Little evidence of local contrast (highest rate at beginning of richer component) was found in any subject. These data show that (a) contrast can occur independently from autoshaping, (b) contrast assays during equal-valued components may produce induction, (c) local contrast in multiple schedules often does not occur, and (d) differential hopper durations can produce autoshaping and contrast. PMID:16812081

  10. 'Faceness' and affectivity: evidence for genetic contributions to distinct components of electrocortical response to human faces.

    PubMed

    Shannon, Robert W; Patrick, Christopher J; Venables, Noah C; He, Sheng

    2013-12-01

    The ability to recognize a variety of different human faces is undoubtedly one of the most important and impressive functions of the human perceptual system. Neuroimaging studies have revealed multiple brain regions (including the FFA, STS, OFA) and electrophysiological studies have identified differing brain event-related potential (ERP) components (e.g., N170, P200) possibly related to distinct types of face information processing. To evaluate the heritability of ERP components associated with face processing, including N170, P200, and LPP, we examined ERP responses to fearful and neutral face stimuli in monozygotic (MZ) and dizygotic (DZ) twins. Concordance levels for early brain response indices of face processing (N170, P200) were found to be stronger for MZ than DZ twins, providing evidence of a heritable basis to each. These findings support the idea that certain key neural mechanisms for face processing are genetically coded. Implications for understanding individual differences in recognition of facial identity and the emotional content of faces are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Sensitivity analysis of key components in large-scale hydroeconomic models

    NASA Astrophysics Data System (ADS)

    Medellin-Azuara, J.; Connell, C. R.; Lund, J. R.; Howitt, R. E.

    2008-12-01

    This paper explores the likely impact of different estimation methods in key components of hydro-economic models such as hydrology and economic costs or benefits, using the CALVIN hydro-economic optimization for water supply in California. In perform our analysis using two climate scenarios: historical and warm-dry. The components compared were perturbed hydrology using six versus eighteen basins, highly-elastic urban water demands, and different valuation of agricultural water scarcity. Results indicate that large scale hydroeconomic hydro-economic models are often rather robust to a variety of estimation methods of ancillary models and components. Increasing the level of detail in the hydrologic representation of this system might not greatly affect overall estimates of climate and its effects and adaptations for California's water supply. More price responsive urban water demands will have a limited role in allocating water optimally among competing uses. Different estimation methods for the economic value of water and scarcity in agriculture may influence economically optimal water allocation; however land conversion patterns may have a stronger influence in this allocation. Overall optimization results of large-scale hydro-economic models remain useful for a wide range of assumptions in eliciting promising water management alternatives.

  12. Deconstructing the Antiviral Neutralizing-Antibody Response: Implications for Vaccine Development and Immunity

    PubMed Central

    VanBlargan, Laura A.

    2016-01-01

    SUMMARY The antibody response plays a key role in protection against viral infections. While antiviral antibodies may reduce the viral burden via several mechanisms, the ability to directly inhibit (neutralize) infection of cells has been extensively studied. Eliciting a neutralizing-antibody response is a goal of many vaccine development programs and commonly correlates with protection from disease. Considerable insights into the mechanisms of neutralization have been gained from studies of monoclonal antibodies, yet the individual contributions and dynamics of the repertoire of circulating antibody specificities elicited by infection and vaccination are poorly understood on the functional and molecular levels. Neutralizing antibodies with the most protective functionalities may be a rare component of a polyclonal, pathogen-specific antibody response, further complicating efforts to identify the elements of a protective immune response. This review discusses advances in deconstructing polyclonal antibody responses to flavivirus infection or vaccination. Our discussions draw comparisons to HIV-1, a virus with a distinct structure and replication cycle for which the antibody response has been extensively investigated. Progress toward deconstructing and understanding the components of polyclonal antibody responses identifies new targets and challenges for vaccination strategies. PMID:27784796

  13. Secure communications using nonlinear silicon photonic keys.

    PubMed

    Grubel, Brian C; Bosworth, Bryan T; Kossey, Michael R; Cooper, A Brinton; Foster, Mark A; Foster, Amy C

    2018-02-19

    We present a secure communication system constructed using pairs of nonlinear photonic physical unclonable functions (PUFs) that harness physical chaos in integrated silicon micro-cavities. Compared to a large, electronically stored one-time pad, our method provisions large amounts of information within the intrinsically complex nanostructure of the micro-cavities. By probing a micro-cavity with a rapid sequence of spectrally-encoded ultrafast optical pulses and measuring the lightwave responses, we experimentally demonstrate the ability to extract 2.4 Gb of key material from a single micro-cavity device. Subsequently, in a secure communication experiment with pairs of devices, we achieve bit error rates below 10 -5 at code rates of up to 0.1. The PUFs' responses are never transmitted over the channel or stored in digital memory, thus enhancing the security of the system. Additionally, the micro-cavity PUFs are extremely small, inexpensive, robust, and fully compatible with telecommunications infrastructure, components, and electronic fabrication. This approach can serve one-time pad or public key exchange applications where high security is required.

  14. Low molecular weight components of pollen alter bronchial epithelial barrier functions.

    PubMed

    Blume, Cornelia; Swindle, Emily J; Gilles, Stefanie; Traidl-Hoffmann, Claudia; Davies, Donna E

    2015-01-01

    The bronchial epithelium plays a key role in providing a protective barrier against many environmental substances of anthropogenic or natural origin which enter the lungs during breathing. Appropriate responses to these agents are critical for regulation of tissue homeostasis, while inappropriate responses may contribute to disease pathogenesis. Here, we compared epithelial barrier responses to different pollen species, characterized the active pollen components and the signaling pathways leading to epithelial activation. Polarized bronchial cells were exposed to extracts of timothy grass (Phleum pratense), ragweed (Ambrosia artemisifolia), mugwort (Artemisia vulgaris), birch (Betula alba) and pine (Pinus sylvestris) pollens. All pollen species caused a decrease in ionic permeability as monitored trans-epithelial electrical resistance (TER) and induced polarized release of mediators analyzed by ELISA, with grass pollen showing the highest activity. Ultrafiltration showed that the responses were due to components <3kDa. However, lipid mediators, including phytoprostane E1, had no effect on TER, and caused only modest induction of mediator release. Reverse-phase chromatography separated 2 active fractions: the most hydrophilic maximally affected cytokine release whereas the other only affected TER. Inhibitor studies revealed that JNK played a more dominant role in regulation of barrier permeability in response to grass pollen exposure, whereas ERK and p38 controlled cytokine release. Adenosine and the flavonoid isorhamnetin present in grass pollen contributed to the overall effect on airway epithelial barrier responses. In conclusion, bronchial epithelial barrier functions are differentially affected by several low molecular weight components released by pollen. Furthermore, ionic permeability and innate cytokine production are differentially regulated.

  15. Civilian Surge: Key to Complex Operations

    DTIC Science & Technology

    2008-12-01

    Division, the unit’s combat operations were reduced by 60 percent over a period of 8 months, enabling Soldiers to focus on improving security, health ... improving the usefulness of existing conflict early warning tools and integrating them with the analysis, prevention, and response components of S /CRS...force protection procedures. Integrated Stabilization Assistance Programs Since 2005, S /CRS has provided technical assistance consultations to

  16. A Review of Fire Effects on Vegetation and Soils in the Great Basin Region: Response and Ecological Site Characteristics

    USDA-ARS?s Scientific Manuscript database

    This review summarizes the state of our knowledge on fire effects on plants and soils in semi-arid ecosystems in the Great Basin Region, including the Columbia River and Snake River basins. It identifies what we know and don’t know and the key components that influence how plants, communities, and ...

  17. An Exploration of the Alienation Experienced by African American Parents from Their Children's Educational Environment

    ERIC Educational Resources Information Center

    Brandon, Regina R.; Higgins, Kyle; Pierce, Tom; Tandy, Richard; Sileo, Nancy

    2010-01-01

    Current research suggests that parents are a key component to the school success of their children. However, in today's world, parents often work long hours, have more than one job, and participate in multiple responsibilities that may limit their participation. Because of the variety of factors that impinge on parents, educators often criticize…

  18. An empirical approach for estimating natural regeneration for the Forest Vegetation Simulator

    Treesearch

    Don Vandendriesche

    2010-01-01

    The “partial” establishment model that is available for most Forest Vegetation Simulator (FVS) geographic variants does not provide an estimate of natural regeneration. Users are responsible for supplying this key aspect of stand development. The process presented for estimating natural regeneration begins by summarizing small tree components based on observations from...

  19. Joint Live Virtual and Constructive (JLVC) Federation Integration Guide. Version 3.1

    DTIC Science & Technology

    2010-01-13

    Coordinate Systems ........................................................................................ 5-22  5.1.3.1  Geocentric Coordinate System...matures. • Data ownership and accessibility. A key component of JWFC’s approach to exercise support is the training audience’s responsibility to...flexibility underscored the necessity of a web-based approach and imposed performance requirements toward which the development team is still working

  20. An ecological model of the habitat mosaic in estuarine nursery areas: Part II – Projecting effects of sea level rise on fish production

    EPA Science Inventory

    Understanding the response of fish populations to habitat change mediated by sea level rise (SLR) is a key component of ecosystem-based management. Yet, no direct link has been established between habitat change due to SLR and fish population production. Here we take a coupled ...

  1. Environmental Literacy Components and Their Promotion by Institutions of Higher Education: An Israeli Case Study

    ERIC Educational Resources Information Center

    Arnon, Sara; Orion, Nir; Carmi, Nurit

    2015-01-01

    The recognition of the key role and moral responsibility of higher education institutions (HEIs) in cultivating the environmental literacy (EL) of their students is growing globally. The current research examined the contribution of HEIs to their students' EL by focusing on an Israeli college as a case-study. A survey was conducted among a…

  2. Affects of road sign wording on visitor survey - non-response bias

    Treesearch

    Susan M. Kocis; Stanley J. Zarnoch; Donald B.K. English

    2004-01-01

    On-site visitor interviewer data collection is a key component of the USDA Forest Service National Visitor Use Monitoring (NVUM) program. In many areas, especially higher speed roads and roads with non-recreation traffic, many vehicles may not stop for an interview. Wording on the sign may condition non-recreation visitors to self-select as to whether or not they...

  3. Gandhian Education in Bali: Globalisations and Cultural Diversity in a Time of Fundamentalisms

    ERIC Educational Resources Information Center

    Tamatea, Laurence

    2006-01-01

    The paper presents findings from a research project undertaken at the Taman Rama Gandhi School in Bali during the first anniversary week of the Bali Bombings in 2003. It explores the school's response to four key components of Gandhi's model of Basic Education ("Nai Talim") and shows that the claimed curriculum is framed by two…

  4. A proper metaphysics for cognitive performance.

    PubMed

    Van Orden, Guy C; Moreno, Miguel A; Holden, John G

    2003-01-01

    The general failure to individuate component causes in cognitive performance suggests the need for an alternative metaphysics. The metaphysics of control hierarchy theory accommodates the fact of self-organization in nature and the possibility that intentional actions are self-organized. One key assumption is that interactions among processes dominate their intrinsic dynamics. Scaling relations in response time variability motivate this assumption in cognitive performance.

  5. TIME FOR COFFEE Represses Accumulation of the MYC2 Transcription Factor to Provide Time-of-Day Regulation of Jasmonate Signaling in Arabidopsis[C][W][OA

    PubMed Central

    Shin, Jieun; Heidrich, Katharina; Sanchez-Villarreal, Alfredo; Parker, Jane E.; Davis, Seth J.

    2012-01-01

    Plants are confronted with predictable daily biotic and abiotic stresses that result from the day–night cycle. The circadian clock provides an anticipation mechanism to respond to these daily stress signals to increase fitness. Jasmonate (JA) is a phytohormone that mediates various growth and stress responses. Here, we found that the circadian-clock component TIME FOR COFFEE (TIC) acts as a negative factor in the JA-signaling pathway. We showed that the tic mutant is hypersensitive to growth-repressive effects of JA and displays altered JA-regulated gene expression. TIC was found to interact with MYC2, a key transcription factor of JA signaling. From this, we discovered that the circadian clock rhythmically regulates JA signaling. TIC is a key determinant in this circadian-gated process, and as a result, the tic mutant is defective in rhythmic JA responses to pathogen infection. TIC acts here by inhibiting MYC2 protein accumulation and by controlling the transcriptional repression of CORONATINE INSENSITIVE1 in an evening-phase–specific manner. Taken together, we propose that TIC acts as an output component of the circadian oscillator to influence JA signaling directly. PMID:22693280

  6. Mitochondrial protein acetylation mediates nutrient sensing of mitochondrial protein synthesis and mitonuclear protein balance.

    PubMed

    Di Domenico, Antonella; Hofer, Annette; Tundo, Federica; Wenz, Tina

    2014-11-01

    Changes in nutrient supply require global metabolic reprogramming to optimize the utilization of the nutrients. Mitochondria as a central component of the cellular metabolism play a key role in this adaptive process. Since mitochondria harbor their own genome, which encodes essential enzymes, mitochondrial protein synthesis is a determinant of metabolic adaptation. While regulation of cytoplasmic protein synthesis in response to metabolic challenges has been studied in great detail, mechanisms which adapt mitochondrial translation in response to metabolic challenges remain elusive. Our results suggest that the mitochondrial acetylation status controlled by Sirt3 and its proposed opponent GCN5L1 is an important regulator of the metabolic adaptation of mitochondrial translation. Moreover, both proteins modulate regulators of cytoplasmic protein synthesis as well as the mitonuclear protein balance making Sirt3 and GCN5L1 key players in synchronizing mitochondrial and cytoplasmic translation. Our results thereby highlight regulation of mitochondrial translation as a novel component in the cellular nutrient sensing scheme and identify mitochondrial acetylation as a new regulatory principle for the metabolic competence of mitochondrial protein synthesis. © 2014 International Union of Biochemistry and Molecular Biology.

  7. A key general stress response motif is regulated non-uniformly by CAMTA transcription factors.

    PubMed

    Benn, Geoffrey; Wang, Chang-Quan; Hicks, Derrick R; Stein, Jeffrey; Guthrie, Cade; Dehesh, Katayoon

    2014-10-01

    Plants cope with environmental challenges by rapidly triggering and synchronizing mechanisms governing stress-specific and general stress response (GSR) networks. The GSR acts rapidly and transiently in response to various stresses, but the underpinning mechanisms have remained elusive. To define GSR regulatory components we have exploited the Rapid Stress Response Element (RSRE), a previously established functional GSR motif, using Arabidopsis plants expressing a 4xRSRE::Luciferase (RSRE::LUC) reporter. Initially, we searched public microarray datasets and found an enrichment of RSRE in promoter sequences of stress genes. Next, we treated RSRE::LUC plants with wounding and a range of rapidly stress-inducible hormones and detected a robust LUC activity solely in response to wounding. Application of two Ca(2+) burst inducers, flagellin22 (flg22) and oligogalacturonic acid, activated RSRE strongly and systemically, while the Ca(2+) chelator ethylene glycol tetraacetic acid (EGTA) significantly reduced wound induction of RSRE::LUC. In line with the signaling function of Ca(2+) in transduction events leading to activation of RSRE, we examined the role of CALMODULIN-BINDING TRANSCRIPTIONAL ACTIVATORs (CAMTAs) in RSRE induction. Transient expression assays displayed CAMTA3 induction of RSRE and not that of the mutated element mRSRE. Treatment of selected camta mutant lines integrated into RSRE::LUC parent plant, with wounding, flg22, and freezing, established a differential function of these CAMTAs in potentiating the activity of RSRE. Wound response studies using camta double mutants revealed a cooperative function of CAMTAs2 and 4 with CAMTA 3 in the RSRE regulation. These studies provide insights into governing components of transduction events and reveal transcriptional modules that tune the expression of a key GSR motif. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  8. 3D Printed Reversible Shape Changing Components with Stimuli Responsive Materials

    PubMed Central

    Mao, Yiqi; Ding, Zhen; Yuan, Chao; Ai, Shigang; Isakov, Michael; Wu, Jiangtao; Wang, Tiejun; Dunn, Martin L.; Qi, H. Jerry

    2016-01-01

    The creation of reversibly-actuating components that alter their shapes in a controllable manner in response to environmental stimuli is a grand challenge in active materials, structures, and robotics. Here we demonstrate a new reversible shape-changing component design concept enabled by 3D printing two stimuli responsive polymers—shape memory polymers and hydrogels—in prescribed 3D architectures. This approach uses the swelling of a hydrogel as the driving force for the shape change, and the temperature-dependent modulus of a shape memory polymer to regulate the time of such shape change. Controlling the temperature and aqueous environment allows switching between two stable configurations – the structures are relatively stiff and can carry load in each – without any mechanical loading and unloading. Specific shape changing scenarios, e.g., based on bending, or twisting in prescribed directions, are enabled via the controlled interplay between the active materials and the 3D printed architectures. The physical phenomena are complex and nonintuitive, and so to help understand the interplay of geometric, material, and environmental stimuli parameters we develop 3D nonlinear finite element models. Finally, we create several 2D and 3D shape changing components that demonstrate the role of key parameters and illustrate the broad application potential of the proposed approach. PMID:27109063

  9. The N170 component is sensitive to face-like stimuli: a study of Chinese Peking opera makeup.

    PubMed

    Liu, Tiantian; Mu, Shoukuan; He, Huamin; Zhang, Lingcong; Fan, Cong; Ren, Jie; Zhang, Mingming; He, Weiqi; Luo, Wenbo

    2016-12-01

    The N170 component is considered a neural marker of face-sensitive processing. In the present study, the face-sensitive N170 component of event-related potentials (ERPs) was investigated with a modified oddball paradigm using a natural face (the standard stimulus), human- and animal-like makeup stimuli, scrambled control images that mixed human- and animal-like makeup pieces, and a grey control image. Nineteen participants were instructed to respond within 1000 ms by pressing the ' F ' or ' J ' key in response to the standard or deviant stimuli, respectively. We simultaneously recorded ERPs, response accuracy, and reaction times. The behavioral results showed that the main effect of stimulus type was significant for reaction time, whereas there were no significant differences in response accuracies among stimulus types. In relation to the ERPs, N170 amplitudes elicited by human-like makeup stimuli, animal-like makeup stimuli, scrambled control images, and a grey control image progressively decreased. A right hemisphere advantage was observed in the N170 amplitudes for human-like makeup stimuli, animal-like makeup stimuli, and scrambled control images but not for grey control image. These results indicate that the N170 component is sensitive to face-like stimuli and reflect configural processing in face recognition.

  10. 3D Printed Reversible Shape Changing Components with Stimuli Responsive Materials

    NASA Astrophysics Data System (ADS)

    Mao, Yiqi; Ding, Zhen; Yuan, Chao; Ai, Shigang; Isakov, Michael; Wu, Jiangtao; Wang, Tiejun; Dunn, Martin L.; Qi, H. Jerry

    2016-04-01

    The creation of reversibly-actuating components that alter their shapes in a controllable manner in response to environmental stimuli is a grand challenge in active materials, structures, and robotics. Here we demonstrate a new reversible shape-changing component design concept enabled by 3D printing two stimuli responsive polymers—shape memory polymers and hydrogels—in prescribed 3D architectures. This approach uses the swelling of a hydrogel as the driving force for the shape change, and the temperature-dependent modulus of a shape memory polymer to regulate the time of such shape change. Controlling the temperature and aqueous environment allows switching between two stable configurations - the structures are relatively stiff and can carry load in each - without any mechanical loading and unloading. Specific shape changing scenarios, e.g., based on bending, or twisting in prescribed directions, are enabled via the controlled interplay between the active materials and the 3D printed architectures. The physical phenomena are complex and nonintuitive, and so to help understand the interplay of geometric, material, and environmental stimuli parameters we develop 3D nonlinear finite element models. Finally, we create several 2D and 3D shape changing components that demonstrate the role of key parameters and illustrate the broad application potential of the proposed approach.

  11. Measuring and improving student engagement in clinical training.

    PubMed

    Lee, Simin; Valtis, Yannis K; Jun, Tomi; Wang, David; Zhang, Biqi; Chung, Esther H; Yu, Amy; Williams, Rachael; Cohen, Marya J

    2018-01-01

    Volunteer service learning activities, including Student Run Clinics (SRCs), are becoming an increasingly popular extracurricular component of medical education. While there are reports that student clinicians generally enjoy their educational experiences at SRCs, it is not understood how to optimize and measure student engagement in them. To identify key drivers of student engagement a tool was created to measure volunteer experience at the Crimson Care Collaborative (CCC), a primary care SRC. CCC volunteers were asked to complete an online engagement survey. Cross-sectional survey data were collected for 149 CCC volunteers (53% response rate). Multivariate linear regression showed that overall 'likelihood to recommend CCC to a friend' was significantly associated with students' perception of the clarity of their role within the clinic, frequency of interprofessional interactions, and overall quality of medical education. Students who volunteer more frequently and for longer periods of time had higher engagement scores. Measuring engagement is feasible in volunteer settings. Engagement appears to be dependent on both structural and experiential components. Easily modifiable components of job design (role definition, expected frequency of volunteering), are key drivers of volunteer engagement.

  12. Exposure to air pollution interacts with obesogenic nutrition to induce tissue-specific response patterns.

    PubMed

    Pardo, Michal; Kuperman, Yael; Levin, Liron; Rudich, Assaf; Haim, Yulia; Schauer, James J; Chen, Alon; Rudich, Yinon

    2018-04-20

    Obesity and exposure to particular matter (PM) have become two leading global threats to public health. However, the exact mechanisms and tissue-specificity of their health effects are largely unknown. Here we investigate whether a metabolic challenge (early nutritional obesity) synergistically interacts with an environmental challenge (PM exposure) to alter genes representing key response pathways, in a tissue-specific manner. Mice subjected to 7 weeks obesogenic nutrition were exposed every other day during the final week and a half to aqueous extracts of PM collected in the city of London (UK). The expression of 61 selected genes representing key response pathways were investigated in lung, liver, white and brown adipose tissues. Principal component analysis (PCA) revealed distinct patterns of expression changes between the 4 tissues, particularly in the lungs and the liver. Surprisingly, the lung responded to the nutrition challenge. The response of these organs to the PM challenge displayed opposite patterns for some key genes, in particular, those related to the Nrf2 pathway. While the contribution to the variance in gene expression changes in mice exposed to the combined challenge were largely similar among the tissues in PCA1, PCA2 exhibited predominant contribution of inflammatory and oxidative stress responses to the variance in the lungs, and a greater contribution of autophagy genes and MAP kinases in adipose tissues. Possible involvement of alterations in DNA methylation was demonstrated by cell-type-specific responses to a methylation inhibitor. Correspondingly, the DNA methyltransferase Dnmt3a2 increased in the lungs but decreased in the liver, demonstrating potential tissue-differential synergism between nutritional and PM exposure. The results suggest that urban PM, containing dissolved metals, interacts with obesogenic nutrition to regulate diverse response pathways including inflammation and oxidative stress, in a tissue-specific manner. Tissue-differential effects on DNA methylation may underlie tissue-specific responses to key stress-response genes such as catalase and Nrf2. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Isolation and Purification of Antigenic Components of Cryptococcus

    PubMed Central

    Wozniak, Karen L.; Levitz, Stuart M.

    2012-01-01

    The encapsulated fungal pathogens Cryptococcus neoformans and Cryptococcus gattii are significant agents of life-threatening infections, particularly in persons with suppressed cell-mediated immunity. This chapter provides detailed methodology for the purification of two of the major antigen fractions of C. neoformans: glucuronoxylomannan (GXM) and mannoprotein (MP). GXM is the primary component of the polysaccharide capsule, which is the major cryptococcal virulence factor. In contrast, MPs have been identified as key antigens that stimulate T-cell responses. Purification of GXM and MP should assist investigators studying the antigenic, biochemical, and virulence properties of Cryptococcus species. PMID:19089377

  14. Role of plant hormones in plant defence responses.

    PubMed

    Bari, Rajendra; Jones, Jonathan D G

    2009-03-01

    Plant hormones play important roles in regulating developmental processes and signaling networks involved in plant responses to a wide range of biotic and abiotic stresses. Significant progress has been made in identifying the key components and understanding the role of salicylic acid (SA), jasmonates (JA) and ethylene (ET) in plant responses to biotic stresses. Recent studies indicate that other hormones such as abscisic acid (ABA), auxin, gibberellic acid (GA), cytokinin (CK), brassinosteroids (BR) and peptide hormones are also implicated in plant defence signaling pathways but their role in plant defence is less well studied. Here, we review recent advances made in understanding the role of these hormones in modulating plant defence responses against various diseases and pests.

  15. Morphine tolerance as a function of ratio schedule: response requirement or unit price?

    PubMed

    Hughes, Christine E; Sigmon, Stacey C; Pitts, Raymond C; Dykstra, Linda A

    2005-05-01

    Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, l-methadone, and cocaine dose-dependently decreased overall response rates in each of the components. When a rate decreasing dose of morphine was administered daily, tolerance, as measured by an increase in the dose that reduced response rates to 50% of control (i.e., the ED50 value), developed in each of the components; however, the degree of tolerance was smallest in the fixed-ratio 90 component (i.e., the ED50 value increased the least). When the l-methadone dose-effect curve was redetermined during the chronic morphine phase, the degree of cross-tolerance conferred to l-methadone was similar across components, suggesting that behavioral variables may not influence the degree of cross-tolerance between opioids. During the chronic phase, the cocaine dose-effect curve shifted to the right for 2 pigeons and to the left for 1 pigeon, which is consistent with predictions based on the lack of pharmacological similarity between morphine and cocaine. When the morphine, l-methadone, and cocaine dose-effect curves were redetermined after chronic morphine administration ended, the morphine and l-methadone ED50s replicated those obtained prior to chronic morphine administration. The morphine data suggest that the fixed-ratio value (i.e., the absolute output) determines the degree of tolerance and not the unit price.

  16. Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes.

    PubMed

    Woo, Hae-Mi; Kang, Ji-Hye; Kawada, Teruo; Yoo, Hoon; Sung, Mi-Kyung; Yu, Rina

    2007-02-13

    Inflammation plays a key role in obesity-related pathologies such as cardiovascular disease, type II diabetes, and several types of cancer. Obesity-induced inflammation entails the enhancement of the recruitment of macrophages into adipose tissue and the release of various proinflammatory proteins from fat tissue. Therefore, the modulation of inflammatory responses in obesity may be useful for preventing or ameliorating obesity-related pathologies. Some spice-derived components, which are naturally occurring phytochemicals, elicit antiobesity and antiinflammatory properties. In this study, we investigated whether active spice-derived components can be applied to the suppression of obesity-induced inflammatory responses. Mesenteric adipose tissue was isolated from obese mice fed a high-fat diet and cultured to prepare an adipose tissue-conditioned medium. Raw 264.7 macrophages were treated with the adipose tissue-conditioned medium with or without active spice-derived components (i.e., diallyl disulfide, allyl isothiocyanate, piperine, zingerone and curcumin). Chemotaxis assay was performed to measure the degree of macrophage migration. Macrophage activation was estimated by measuring tumor necrosis factor-alpha (TNF-alpha), nitric oxide, and monocyte chemoattractant protein-1 (MCP-1) concentrations. The active spice-derived components markedly suppressed the migration of macrophages induced by the mesenteric adipose tissue-conditioned medium in a dose-dependent manner. Among the active spice-derived components studied, allyl isothiocyanate, zingerone, and curcumin significantly inhibited the cellular production of proinflammatory mediators such as TNF-alpha and nitric oxide, and significantly inhibited the release of MCP-1 from 3T3-L1 adipocytes. Our findings suggest that the spice-derived components can suppress obesity-induced inflammatory responses by suppressing adipose tissue macrophage accumulation or activation and inhibiting MCP-1 release from adipocytes. These spice-derived components may have a potential to improve chronic inflammatory conditions in obesity.

  17. The Xanthomonas oryzae pv. oryzae PhoPQ Two-Component System Is Required for AvrXA21 Activity, hrpG Expression, and Virulence▿ †

    PubMed Central

    Lee, Sang-Won; Jeong, Kyu-Sik; Han, Sang-Wook; Lee, Seung-Eun; Phee, Bong-Kwan; Hahn, Tae-Ryong; Ronald, Pamela

    2008-01-01

    The rice pathogen recognition receptor, XA21, confers resistance to Xanthomonas oryzae pv. oryzae strains producing the type one system-secreted molecule, AvrXA21. X. oryzae pv. oryzae requires a regulatory two-component system (TCS) called RaxRH to regulate expression of eight rax (required for AvrXA21 activity) genes and to sense population cell density. To identify other key components in this critical regulatory circuit, we assayed proteins expressed in a raxR gene knockout strain. This survey led to the identification of the phoP gene encoding a response regulator that is up-regulated in the raxR knockout strain. Next we generated a phoP knockout strain and found it to be impaired in X. oryzae pv. oryzae virulence and no longer able to activate the response regulator HrpG (hypersensitive reaction and pathogenicity G) in response to low levels of Ca2+. The impaired virulence of the phoP knockout strain can be partially complemented by constitutive expression of hrpG, indicating that PhoP controls a key aspect of X. oryzae pv. oryzae virulence through regulation of hrpG. A gene encoding the cognate putative histidine protein kinase, phoQ, was also isolated. Growth curve analysis revealed that AvrXA21 activity is impaired in a phoQ knockout strain as reflected by enhanced growth of this strain in rice lines carrying XA21. These results suggest that the X. oryzae pv. oryzae PhoPQ TCS functions in virulence and in the production of AvrXA21 in partnership with RaxRH. PMID:18203830

  18. Cue response dissociates inhibitory processes: task identity information is related to backward inhibition but not to competitor rule suppression.

    PubMed

    Regev, Shirley; Meiran, Nachshon

    2017-01-01

    In task switching, a conflict between competing task-sets is resolved by inhibiting the interfering task-set. Recent models have proposed a framework of the task-set as composed of two hierarchical components: abstract task identity (e.g., respond to quantity) and more concrete task rules (e.g., category-response rules mapping the categories "one" and "three" to the left and right keys, respectively). The present study explored whether task-set inhibition is the outcome of a general control process or whether it reflects multiple inhibitory processes, each targeting a different component of the competing task-set. To this end, two effects of task-set inhibition were examined: backward inhibition (BI), reflecting the suppression of a just-performed task-set that is no longer relevant; and, competitor rule suppression (CRS), reflecting the suppression of an irrelevant task-set that generates a response conflict. In two task switching experiments, each involving three tasks, we asked participants to make two responses: a cue response, indicating the identity of the relevant task (e.g., "Color"), and a target response requiring the implementation of the task rule (e.g., "Red"). The results demonstrate that BI, but not CRS, appears in cue responses, and thus, suggests that BI reflects inhibition that influences representations related to abstract task identity, rather than (just) competing responses or response rules. These results support a dissociation between inhibitory processes in task switching. The current findings also provide further evidence for a multi-component conceptualization of task-set and task-set inhibition.

  19. Comparative Analysis of Wolbachia Genomes Reveals Streamlining and Divergence of Minimalist Two-Component Systems

    PubMed Central

    Christensen, Steen; Serbus, Laura Renee

    2015-01-01

    Two-component regulatory systems are commonly used by bacteria to coordinate intracellular responses with environmental cues. These systems are composed of functional protein pairs consisting of a sensor histidine kinase and cognate response regulator. In contrast to the well-studied Caulobacter crescentus system, which carries dozens of these pairs, the streamlined bacterial endosymbiont Wolbachia pipientis encodes only two pairs: CckA/CtrA and PleC/PleD. Here, we used bioinformatic tools to compare characterized two-component system relays from C. crescentus, the related Anaplasmataceae species Anaplasma phagocytophilum and Ehrlichia chaffeensis, and 12 sequenced Wolbachia strains. We found the core protein pairs and a subset of interacting partners to be highly conserved within Wolbachia and these other Anaplasmataceae. Genes involved in two-component signaling were positioned differently within the various Wolbachia genomes, whereas the local context of each gene was conserved. Unlike Anaplasma and Ehrlichia, Wolbachia two-component genes were more consistently found clustered with metabolic genes. The domain architecture and key functional residues standard for two-component system proteins were well-conserved in Wolbachia, although residues that specify cognate pairing diverged substantially from other Anaplasmataceae. These findings indicate that Wolbachia two-component signaling pairs share considerable functional overlap with other α-proteobacterial systems, whereas their divergence suggests the potential for regulatory differences and cross-talk. PMID:25809075

  20. Molecular response of canola to salt stress: insights on tolerance mechanisms.

    PubMed

    Shokri-Gharelo, Reza; Noparvar, Pouya Motie

    2018-01-01

    Canola ( Brassica napus L. ) is widely cultivated around the world for the production of edible oils and biodiesel fuel. Despite many canola varieties being described as 'salt-tolerant', plant yield and growth decline drastically with increasing salinity. Although many studies have resulted in better understanding of the many important salt-response mechanisms that control salt signaling in plants, detoxification of ions, and synthesis of protective metabolites, the engineering of salt-tolerant crops has only progressed slowly. Genetic engineering has been considered as an efficient method for improving the salt tolerance of canola but there are many unknown or little-known aspects regarding canola response to salinity stress at the cellular and molecular level. In order to develop highly salt-tolerant canola, it is essential to improve knowledge of the salt-tolerance mechanisms, especially the key components of the plant salt-response network. In this review, we focus on studies of the molecular response of canola to salinity to unravel the different pieces of the salt response puzzle. The paper includes a comprehensive review of the latest studies, particularly of proteomic and transcriptomic analysis, including the most recently identified canola tolerance components under salt stress, and suggests what researchers should focus on in future studies.

  1. Evidence for the Induction of Key Components of the NOTCH Signaling Pathway via Deltamethrin and Azamethiphos Treatment in the Sea Louse Caligus rogercresseyi

    PubMed Central

    Boltaña, Sebastian; Chávez-Mardones, Jaqueline; Valenzuela-Muñoz, Valentina; Gallardo-Escárate, Cristian

    2016-01-01

    The extensive use of organophosphates and pyrethroids in the aquaculture industry has negatively impacted parasite sensitivity to the delousing effects of these antiparasitics, especially among sea lice species. The NOTCH signaling pathway is a positive regulator of ABC transporter subfamily C expression and plays a key role in the generation and modulation of pesticide resistance. However, little is known about the molecular mechanisms behind pesticide resistance, partly due to the lack of genomic and molecular information on the processes involved in the resistance mechanism of sea lice. Next-generation sequencing technologies provide an opportunity for rapid and cost-effective generation of genome-scale data. The present study, through RNA-seq analysis, determined that the sea louse Caligus rogercresseyi (C. rogercresseyi) specifically responds to the delousing drugs azamethiphos and deltamethrin at the transcriptomic level by differentially activating mRNA of the NOTCH signaling pathway and of ABC genes. These results suggest that frequent antiparasitic application may increase the activity of inhibitory mRNA components, thereby promoting inhibitory NOTCH output and conditions for increased resistance to delousing drugs. Moreover, data analysis underscored that key functions of NOTCH/ABC components were regulated during distinct phases of the drug response, thus indicating resistance modifications in C. rogercresseyi resulting from the frequent use of organophosphates and pyrethroids. PMID:27187362

  2. Evidence for the Induction of Key Components of the NOTCH Signaling Pathway via Deltamethrin and Azamethiphos Treatment in the Sea Louse Caligus rogercresseyi.

    PubMed

    Boltaña, Sebastian; Chávez-Mardones, Jaqueline; Valenzuela-Muñoz, Valentina; Gallardo-Escárate, Cristian

    2016-05-12

    The extensive use of organophosphates and pyrethroids in the aquaculture industry has negatively impacted parasite sensitivity to the delousing effects of these antiparasitics, especially among sea lice species. The NOTCH signaling pathway is a positive regulator of ABC transporter subfamily C expression and plays a key role in the generation and modulation of pesticide resistance. However, little is known about the molecular mechanisms behind pesticide resistance, partly due to the lack of genomic and molecular information on the processes involved in the resistance mechanism of sea lice. Next-generation sequencing technologies provide an opportunity for rapid and cost-effective generation of genome-scale data. The present study, through RNA-seq analysis, determined that the sea louse Caligus rogercresseyi (C. rogercresseyi) specifically responds to the delousing drugs azamethiphos and deltamethrin at the transcriptomic level by differentially activating mRNA of the NOTCH signaling pathway and of ABC genes. These results suggest that frequent antiparasitic application may increase the activity of inhibitory mRNA components, thereby promoting inhibitory NOTCH output and conditions for increased resistance to delousing drugs. Moreover, data analysis underscored that key functions of NOTCH/ABC components were regulated during distinct phases of the drug response, thus indicating resistance modifications in C. rogercresseyi resulting from the frequent use of organophosphates and pyrethroids.

  3. Training initiatives within the AFHSC-Global Emerging Infections Surveillance and Response System: support for IHR (2005)

    PubMed Central

    2011-01-01

    Training is a key component of building capacity for public health surveillance and response, but has often been difficult to quantify. During fiscal 2009, the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) supported 18 partner organizations in conducting 123 training initiatives in 40 countries for 3,130 U.S. military, civilian and host-country personnel. The training assisted with supporting compliance with International Health Regulations, IHR (2005). Training activities in pandemic preparedness, outbreak investigation and response, emerging infectious disease (EID) surveillance and pathogen diagnostic techniques were expanded significantly. By engaging local health and other government officials and civilian institutions, the U.S. military’s role as a key stakeholder in global public health has been strengthened and has contributed to EID-related surveillance, research and capacity-building initiatives specified elsewhere in this issue. Public health and emerging infections surveillance training accomplished by AFHSC-GEIS and its Department of Defense (DoD) partners during fiscal 2009 will be tabulated and described. PMID:21388565

  4. Role of Complement on Broken Surfaces After Trauma.

    PubMed

    Huber-Lang, Markus; Ignatius, Anita; Brenner, Rolf E

    2015-01-01

    Activation of both the complement and coagulation cascade after trauma and subsequent local and systemic inflammatory response represent a major scientific and clinical problem. After severe tissue injury and bone fracture, exposure of innate immunity to damaged cells and molecular debris is considered a main trigger of the posttraumatic danger response. However, the effects of cellular fragments (e.g., histones) on complement activation remain enigmatic. Furthermore, direct effects of "broken" bone and cartilage surfaces on the fluid phase response of complement and its interaction with key cells of connective tissues are still unknown. Here, we summarize data suggesting direct and indirect complement activation by extracellular and cellular danger associated molecular patterns. In addition, key complement components and the corresponding receptors (such as C3aR, C5aR) have been detected on "exposed surfaces" of the damaged regions. On a cellular level, multiple effects of complement activation products on osteoblasts, osteoclasts, chondrocytes and mesenchymal stem cells have been found.In conclusion, the complement system may be activated by trauma-altered surfaces and is crucially involved in connective tissue healing and posttraumatic systemic inflammatory response.

  5. Conservation and divergence of the cyclic adenosine monophosphate-protein kinase A (cAMP–PKA) pathway in two plant-pathogenic fungi: Fusarium graminearum and F. verticillioides

    USDA-ARS?s Scientific Manuscript database

    The cyclic AMP (cAMP)-PKA pathway is a central signaling cascade that transmits extracellular stimuli and governs cell responses through the second messenger cAMP. The importance of cAMP signaling in fungal biology has been well documented. Two key conserved components, adenylate cyclase (AC) and ca...

  6. The Computer and Personal Privacy, Part II: The Emerging Worldwide Response to the Threat to Privacy from Computer Databases.

    ERIC Educational Resources Information Center

    Rubin, Michael Rogers

    1988-01-01

    The second of three articles on abusive data collection and usage practices and their effect on personal privacy, discusses the evolution of data protection laws worldwide, and compares the scope, major provisions, and enforcement components of the laws. A chronology of key events in the regulation of computer databanks in included. (1 reference)…

  7. Investigating the Variables in a Mock Exam Study Session Designed to Improve Student Exam Performance in an Undergraduate Behavior Modification and Therapy Course

    ERIC Educational Resources Information Center

    Dotson, Wesley H.

    2010-01-01

    The purpose of the present study was to identify components of an optional mock exam review session (e.g. requiring students to write answers, providing students grading keys for questions) responsible for improvements in student performance on application-based short-essay exams in an undergraduate behavior modification course. Both…

  8. RACLETTE: a model for evaluating the thermal response of plasma facing components to slow high power plasma transients. Part I: Theory and description of model capabilities

    NASA Astrophysics Data System (ADS)

    Raffray, A. René; Federici, Gianfranco

    1997-04-01

    RACLETTE (Rate Analysis Code for pLasma Energy Transfer Transient Evaluation), a comprehensive but relatively simple and versatile model, was developed to help in the design analysis of plasma facing components (PFCs) under 'slow' high power transients, such as those associated with plasma vertical displacement events. The model includes all the key surface heat transfer processes such as evaporation, melting, and radiation, and their interaction with the PFC block thermal response and the coolant behaviour. This paper represents part I of two sister and complementary papers. It covers the model description, calibration and validation, and presents a number of parametric analyses shedding light on and identifying trends in the PFC armour block response to high plasma energy deposition transients. Parameters investigated include the plasma energy density and deposition time, the armour thickness and the presence of vapour shielding effects. Part II of the paper focuses on specific design analyses of ITER plasma facing components (divertor, limiter, primary first wall and baffle), including improvements in the thermal-hydraulic modeling required for better understanding the consequences of high energy deposition transients in particular for the ITER limiter case.

  9. Zinc induces distinct changes in the metabolism of reactive oxygen and nitrogen species (ROS and RNS) in the roots of two Brassica species with different sensitivity to zinc stress

    PubMed Central

    Feigl, Gábor; Lehotai, Nóra; Molnár, Árpád; Ördög, Attila; Rodríguez-Ruiz, Marta; Palma, José M.; Corpas, Francisco J.; Erdei, László; Kolbert, Zsuzsanna

    2015-01-01

    Background and Aims Zinc (Zn) is an essential micronutrient naturally present in soils, but anthropogenic activities can lead to accumulation in the environment and resulting damage to plants. Heavy metals such as Zn can induce oxidative stress and the generation of reactive oxygen and nitrogen species (ROS and RNS), which can reduce growth and yield in crop plants. This study assesses the interplay of these two families of molecules in order to evaluate the responses in roots of two Brassica species under high concentrations of Zn. Methods Nine-day-old hydroponically grown Brassica juncea (Indian mustard) and B. napus (oilseed rape) seedlings were treated with ZnSO4 (0, 50, 150 and 300 µm) for 7 d. Stress intensity was assessed through analyses of cell wall damage and cell viability. Biochemical and cellular techniques were used to measure key components of the metabolism of ROS and RNS including lipid peroxidation, enzymatic antioxidants, protein nitration and content of superoxide radical (O2·−), nitric oxide (NO) and peroxynitrite (ONOO−). Key Results Analysis of morphological root damage and alterations of microelement homeostasis indicate that B. juncea is more tolerant to Zn stress than B. napus. ROS and RNS parameters suggest that the oxidative components are predominant compared with the nitrosative components in the root system of both species. Conclusions The results indicate a clear relationship between ROS and RNS metabolism as a mechanism of response against stress caused by an excess of Zn. The oxidative stress components seem to be more dominant than the elements of the nitrosative stress in the root system of these two Brassica species. PMID:25538112

  10. An Efficient Extraction Method for Fragrant Volatiles from Jasminum sambac (L.) Ait.

    PubMed

    Ye, Qiuping; Jin, Xinyi; Zhu, Xinliang; Lin, Tongxiang; Hao, Zhilong; Yang, Qian

    2015-01-01

    The sweet smell of aroma of Jasminum sambac (L.) Ait. is releasing while the flowers are blooming. Although components of volatile oil have been extensively studied, there are problematic issues, such as low efficiency of yield, flavour distortion. Here, the subcritical fluid extraction (SFE) was performed to extract fragrant volatiles from activated carbon that had absorbed the aroma of jasmine flowers. This novel method could effectively obtain main aromatic compounds with quality significantly better than solvent extraction (SE). Based on the analysis data with response surface methodology (RSM), we optimized the extraction conditions which consisted of a temperature of 44°C, a solvent-to-material ratio of 3.5:1, and an extraction time of 53 min. Under these conditions, the extraction yield was 4.91%. Furthermore, the key jasmine essence oil components, benzyl acetate and linalool, increase 7 fold and 2 fold respectively which lead to strong typical smell of the jasmine oil. The new method can reduce spicy components which lead to the essential oils smelling sweeter. Thus, the quality of the jasmine essence oil was dramatically improved and yields based on the key component increased dramatically. Our results provide a new effective technique for extracting fragrant volatiles from jasmine flowers.

  11. Phenology of mixed woody-herbaceous ecosystems following extreme events: net and differential responses.

    PubMed

    Rich, Paul M; Breshears, David D; White, Amanda B

    2008-02-01

    Ecosystem responses to key climate drivers are reflected in phenological dynamics such as the timing and degree of "green-up" that integrate responses over spatial scales from individual plants to ecosystems. This integration is clearest in ecosystems dominated by a single species or life form, such as seasonally dynamic grasslands or more temporally constant evergreen forests. Yet many ecosystems have substantial contribution of cover from both herbaceous and woody evergreen plants. Responses of mixed woody-herbaceous ecosystems to climate are of increasing concern due to their extensive nature, the potential for such systems to yield more complex responses than those dominated by a single life form, and projections that extreme climate and weather events will increase in frequency and intensity with global warming. We present responses of a mixed woody-herbaceous ecosystem type to an extreme event: regional-scale piñon pine mortality following an extended drought and the subsequent herbaceous green-up following the first wet period after the drought. This example highlights how reductions in greenness of the slower, more stable evergreen woody component can rapidly be offset by increases associated with resources made available to the relatively more responsive herbaceous component. We hypothesize that such two-phase phenological responses to extreme events are characteristic of many mixed woody-herbaceous ecosystems.

  12. Albumin Antioxidant Response to Stress in Diabetic Nephropathy Progression

    PubMed Central

    Medina-Navarro, Rafael; Corona-Candelas, Itzia; Barajas-González, Saúl; Díaz-Flores, Margarita; Durán-Reyes, Genoveva

    2014-01-01

    Background A new component of the protein antioxidant capacity, designated Response Surplus (RS), was recently described. A major feature of this component is the close relationship between protein antioxidant capacity and molecular structure. Oxidative stress is associated with renal dysfunction in patients with renal failure, and plasma albumin is the target of massive oxidation in nephrotic syndrome and diabetic nephropathy. The aim of the present study was to explore the albumin redox state and the RS component of human albumin isolated from diabetic patients with progressive renal damage. Methods/Principal Findings Serum aliquots were collected and albumin isolated from 125 diabetic patients divided into 5 groups according to their estimated glomerular filtration rate (GFR). In addition to clinical and biochemical variables, the albumin redox state, including antioxidant capacity, thiol group content, and RS component, were evaluated. The albumin antioxidant capacity and thiol group content were reciprocally related to the RS component in association with GFR reduction. The GFR decline and RS component were significantly negatively correlated (R = –0.83, p<0.0001). Age, creatinine, thiol groups, and antioxidant capacity were also significantly related to the GFR decline (R = –0.47, p<0.001; R = –0.68, p<0.0001; R = 0.44, p<0.001; and R = 0.72, p<0.0001). Conclusion/Significance The response of human albumin to stress in relation to the progression of diabetic renal disease was evaluated. The findings confirm that the albumin molecular structure is closely related to its redox state, and is a key factor in the progression of diabetes nephropathy. PMID:25187963

  13. Genome wide analysis of the complete GlnR nitrogen-response regulon in Mycobacterium smegmatis

    PubMed Central

    2013-01-01

    Background Nitrogen is an essential element for bacterial growth and an important component of biological macromolecules. Consequently, responding to nitrogen limitation is critical for bacterial survival and involves the interplay of signalling pathways and transcriptional regulation of nitrogen assimilation and scavenging genes. In the soil dwelling saprophyte Mycobacterium smegmatis the OmpR-type response regulator GlnR is thought to mediate the transcriptomic response to nitrogen limitation. However, to date only ten genes have been shown to be in the GlnR regulon, a vastly reduced number compared to other organisms. Results We investigated the role of GlnR in the nitrogen limitation response and determined the entire GlnR regulon, by combining expression profiling of M. smegmatis wild type and glnR deletion mutant, with GlnR-specific chromatin immunoprecipitation and high throughput sequencing. We identify 53 GlnR binding sites during nitrogen limitation that control the expression of over 100 genes, demonstrating that GlnR is the regulator controlling the assimilation and utilisation of nitrogen. We also determine a consensus GlnR binding motif and identify key residues within the motif that are required for specific GlnR binding. Conclusions We have demonstrated that GlnR is the global nitrogen response regulator in M. smegmatis, directly regulating the expression of more than 100 genes. GlnR controls key nitrogen stress survival processes including primary nitrogen metabolism pathways, the ability to utilise nitrate and urea as alternative nitrogen sources, and the potential to use cellular components to provide a source of ammonium. These studies further our understanding of how mycobacteria survive nutrient limiting conditions. PMID:23642041

  14. The Motivational Salience of Faces Is Related to Both Their Valence and Dominance.

    PubMed

    Wang, Hongyi; Hahn, Amanda C; DeBruine, Lisa M; Jones, Benedict C

    2016-01-01

    Both behavioral and neural measures of the motivational salience of faces are positively correlated with their physical attractiveness. Whether physical characteristics other than attractiveness contribute to the motivational salience of faces is not known, however. Research with male macaques recently showed that more dominant macaques' faces hold greater motivational salience. Here we investigated whether dominance also contributes to the motivational salience of faces in human participants. Principal component analysis of third-party ratings of faces for multiple traits revealed two orthogonal components. The first component ("valence") was highly correlated with rated trustworthiness and attractiveness. The second component ("dominance") was highly correlated with rated dominance and aggressiveness. Importantly, both components were positively and independently related to the motivational salience of faces, as assessed from responses on a standard key-press task. These results show that at least two dissociable components underpin the motivational salience of faces in humans and present new evidence for similarities in how humans and non-human primates respond to facial cues of dominance.

  15. The role of hemocytes in A. gambiae antiplasmodial immunity

    PubMed Central

    Ramirez, Jose Luis; Garver, Lindsey S.; Brayner, Fábio André; Alves, Luiz Carlos; Rodrigues, Janneth; Molina-Cruz, Alvaro; Barillas-Mury, Carolina

    2013-01-01

    Hemocytes synthesize key components of the mosquito complement-like system, but their role in the activation of antiplasmodial responses has not been established. The effect of activating Toll signaling in hemocytes on Plasmodium survival was investigated by transferring hemocytes or cell-free hemolymph from donor mosquitoes in which the suppressor cactus was silenced. These transfers greatly enhanced antiplasmodial immunity, indicating that hemocytes are active players in the activation of the complement-like system, through an effector(s) regulated by the Toll pathway. A comparative analysis of hemocyte populations between susceptible (S) G3 and the refractory (R) L3-5 A. gambiae mosquito strains did not reveal significant differences under basal conditions or in response to Plasmodium berghei infection. The response of S mosquitoes to different Plasmodium species revealed similar kinetics following infection with P. berghei, P. yoelii or P. falciparum, but the strength of the priming response was stronger in less compatible mosquito-parasite pairs. The Toll, Imd, STAT or JNK signaling cascades were not essential for the production of hemocyte differentiation factor (HDF) in response to P. berghei infection, but disruption of Toll, STAT or JNK abolished hemocyte differentiation in response to HDF. We conclude that hemocytes are key mediators of A. gambiae antiplasmodial responses. PMID:23886925

  16. Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster

    PubMed Central

    Lindström, Riitta; Lindholm, Päivi; Kallijärvi, Jukka; Palgi, Mari; Saarma, Mart; Heino, Tapio I.

    2016-01-01

    Disturbances in the homeostasis of endoplasmic reticulum (ER) referred to as ER stress is involved in a variety of human diseases. ER stress activates unfolded protein response (UPR), a cellular mechanism the purpose of which is to restore ER homeostasis. Previous studies show that Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) is an important novel component in the regulation of UPR. In vertebrates, MANF is upregulated by ER stress and protects cells against ER stress-induced cell death. Biochemical studies have revealed an interaction between mammalian MANF and GRP78, the major ER chaperone promoting protein folding. In this study we discovered that the upregulation of MANF expression in response to drug-induced ER stress is conserved between Drosophila and mammals. Additionally, by using a genetic in vivo approach we found genetic interactions between Drosophila Manf and genes encoding for Drosophila homologues of GRP78, PERK and XBP1, the key components of UPR. Our data suggest a role for Manf in the regulation of Drosophila UPR. PMID:26975047

  17. Security of quantum key distribution with multiphoton components

    PubMed Central

    Yin, Hua-Lei; Fu, Yao; Mao, Yingqiu; Chen, Zeng-Bing

    2016-01-01

    Most qubit-based quantum key distribution (QKD) protocols extract the secure key merely from single-photon component of the attenuated lasers. However, with the Scarani-Acin-Ribordy-Gisin 2004 (SARG04) QKD protocol, the unconditionally secure key can be extracted from the two-photon component by modifying the classical post-processing procedure in the BB84 protocol. Employing the merits of SARG04 QKD protocol and six-state preparation, one can extract secure key from the components of single photon up to four photons. In this paper, we provide the exact relations between the secure key rate and the bit error rate in a six-state SARG04 protocol with single-photon, two-photon, three-photon, and four-photon sources. By restricting the mutual information between the phase error and bit error, we obtain a higher secure bit error rate threshold of the multiphoton components than previous works. Besides, we compare the performances of the six-state SARG04 with other prepare-and-measure QKD protocols using decoy states. PMID:27383014

  18. Key components of financial-analysis education for clinical nurses.

    PubMed

    Lim, Ji Young; Noh, Wonjung

    2015-09-01

    In this study, we identified key components of financial-analysis education for clinical nurses. We used a literature review, focus group discussions, and a content validity index survey to develop key components of financial-analysis education. First, a wide range of references were reviewed, and 55 financial-analysis education components were gathered. Second, two focus group discussions were performed; the participants were 11 nurses who had worked for more than 3 years in a hospital, and nine components were agreed upon. Third, 12 professionals, including professors, nurse executive, nurse managers, and an accountant, participated in the content validity index. Finally, six key components of financial-analysis education were selected. These key components were as follows: understanding the need for financial analysis, introduction to financial analysis, reading and implementing balance sheets, reading and implementing income statements, understanding the concepts of financial ratios, and interpretation and practice of financial ratio analysis. The results of this study will be used to develop an education program to increase financial-management competency among clinical nurses. © 2015 Wiley Publishing Asia Pty Ltd.

  19. Innate immune responses in central nervous system inflammation.

    PubMed

    Finsen, Bente; Owens, Trevor

    2011-12-01

    In autoimmune diseases of the central nervous system (CNS), innate glial cell responses play a key role in determining the outcome of leukocyte infiltration. Access of leukocytes is controlled via complex interactions with glial components of the blood-brain barrier that include angiotensin II receptors on astrocytes and immunoregulatory mediators such as Type I interferons which regulate cellular traffic. Myeloid cells at the blood-brain barrier present antigen to T cells and influence cytokine effector function. Myelin-specific T cells interact with microglia and promote differentiation of oligodendrocyte precursor cells in response to axonal injury. These innate responses offer potential targets for immunomodulatory therapy. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  20. Biologic Therapy and Asthma.

    PubMed

    Viswanathan, Ravi K; Busse, William W

    2018-02-01

    Although airway inflammation is an intrinsic and key feature of asthma, this response varies in its intensity and translation to clinical characteristics and responsiveness to treatment. The observations that clinical heterogeneity is an important aspect of asthma and a feature that likely dictates and determines responses to treatment in severe asthma, patient responsiveness to medication is incomplete, and risks for exacerbation are increased. The development of biologics, which target selected and specific components of inflammation, has been a promising advance to achieve asthma control in patients with severe disease. This article reviews the current biologics available and under development and how their use has affected asthma and which subpopulations appear to benefit the greatest. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  1. Alternative Splicing Control of Abiotic Stress Responses.

    PubMed

    Laloum, Tom; Martín, Guiomar; Duque, Paula

    2018-02-01

    Alternative splicing, which generates multiple transcripts from the same gene, is an important modulator of gene expression that can increase proteome diversity and regulate mRNA levels. In plants, this post-transcriptional mechanism is markedly induced in response to environmental stress, and recent studies have identified alternative splicing events that allow rapid adjustment of the abundance and function of key stress-response components. In agreement, plant mutants defective in splicing factors are severely impaired in their response to abiotic stress. Notably, mounting evidence indicates that alternative splicing regulates stress responses largely by targeting the abscisic acid (ABA) pathway. We review here current understanding of post-transcriptional control of plant stress tolerance via alternative splicing and discuss research challenges for the near future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Attribution of Observed Streamflow Changes in Key British Columbia Drainage Basins

    NASA Astrophysics Data System (ADS)

    Najafi, Mohammad Reza; Zwiers, Francis W.; Gillett, Nathan P.

    2017-11-01

    We study the observed decline in summer streamflow in four key river basins in British Columbia (BC), Canada, using a formal detection and attribution (D&A) analysis procedure. Reconstructed and simulated streamflow is generated using the semidistributed variable infiltration capacity hydrologic model, which is driven by 1/16° gridded observations and downscaled climate model data from the Coupled Model Intercomparison Project phase 5 (CMIP5), respectively. The internal variability of the regional hydrologic components using 5100 years of streamflow was simulated using CMIP5 preindustrial control runs. Results show that the observed changes in summer streamflow are inconsistent with simulations representing the responses to natural forcing factors alone, while the response to anthropogenic and natural forcing factors combined is detected in these changes. A two-signal D&A analysis indicates that the effects of anthropogenic (ANT) forcing factors are discernable from natural forcing in BC, albeit with large uncertainties.

  3. Implementing corporate wellness programs: a business approach to program planning.

    PubMed

    Helmer, D C; Dunn, L M; Eaton, K; Macedonio, C; Lubritz, L

    1995-11-01

    1. Support of key decision makers is critical to the successful implementation of a corporate wellness program. Therefore, the program implementation plan must be communicated in a format and language readily understood by business people. 2. A business approach to corporate wellness program planning provides a standardized way to communicate the implementation plan. 3. A business approach incorporates the program planning components in a format that ranges from general to specific. This approach allows for flexibility and responsiveness to changes in program planning. 4. Components of the business approach are the executive summary, purpose, background, ground rules, approach, requirements, scope of work, schedule, and financials.

  4. Target-induced formation of neuraminidase inhibitors from in vitro virtual combinatorial libraries

    PubMed Central

    Hochgürtel, Matthias; Kroth, Heiko; Piecha, Dorothea; Hofmann, Michael W.; Nicolau, Claude; Krause, Sonja; Schaaf, Otmar; Sonnenmoser, Gabriele; Eliseev, Alexey V.

    2002-01-01

    Neuraminidase, a key enzyme responsible for influenza virus propagation, has been used as a template for selective synthesis of small subsets of its own inhibitors from theoretically highly diverse dynamic combinatorial libraries. We show that the library building blocks, aldehydes and amines, form significant amounts of the library components resulting from their coupling by reductive amination only in the presence of the enzyme. The target amplifies the best hits at least 120-fold. The dynamic libraries synthesized and screened in such an in vitro virtual mode form the components that possess high inhibitory activity, as confirmed by enzyme assays with independently synthesized individual compounds. PMID:11891312

  5. Spectrum response estimation for deep-water floating platforms via retardation function representation

    NASA Astrophysics Data System (ADS)

    Liu, Fushun; Liu, Chengcheng; Chen, Jiefeng; Wang, Bin

    2017-08-01

    The key concept of spectrum response estimation with commercial software, such as the SESAM software tool, typically includes two main steps: finding a suitable loading spectrum and computing the response amplitude operators (RAOs) subjected to a frequency-specified wave component. In this paper, we propose a nontraditional spectrum response estimation method that uses a numerical representation of the retardation functions. Based on estimated added mass and damping matrices of the structure, we decompose and replace the convolution terms with a series of poles and corresponding residues in the Laplace domain. Then, we estimate the power density corresponding to each frequency component using the improved periodogram method. The advantage of this approach is that the frequency-dependent motion equations in the time domain can be transformed into the Laplace domain without requiring Laplace-domain expressions for the added mass and damping. To validate the proposed method, we use a numerical semi-submerged pontoon from the SESAM. The numerical results show that the responses of the proposed method match well with those obtained from the traditional method. Furthermore, the estimated spectrum also matches well, which indicates its potential application to deep-water floating structures.

  6. Earthshots: Satellite images of environmental change – Garden City, Kansas, USA

    USGS Publications Warehouse

    ,

    2013-01-01

    This area uses irrigation water from the Ogallala Aquifer, one of the world's largest aquifers, which underlies an area from Wyoming to Texas. Landsat images are useful for measuring irrigated crop acreage, a key component of modeling aquifer response to changes in water use. Landsat is also used to monitor the depletion of the aquifer, which is affected by not only the irrigation but also drought.

  7. A Brief Report of the Diagnostic Accuracy of Oral Reading Fluency and Reading Inventory Levels for Reading Failure Risk among Second- and Third-Grade Students

    ERIC Educational Resources Information Center

    Parker, David C.; Zaslofsky, Anne F.; Burns, Matthew K.; Kanive, Rebecca; Hodgson, Jennifer; Scholin, Sarah E.; Klingbeil, David A.

    2015-01-01

    The availability of psychometrically sound and usable universal screeners is a key component to successful early identification within a response-to-intervention model. The purpose of this study was to compare the diagnostic accuracy of oral reading fluency (ORF) and an informal reading inventory for identifying students considered at risk for…

  8. Uncontrolled eating in adolescents: The role of impulsivity and automatic approach bias for food.

    PubMed

    Booth, Charlotte; Spronk, Desiree; Grol, Maud; Fox, Elaine

    2018-01-01

    Obesity is a global problem reaching epidemic proportions and can be explained by unhealthy eating and sedentary lifestyles. Understanding the psychological processes underlying unhealthy eating behaviour is crucial for the development of effective obesity prevention programmes. Dual-process models implicate the interplay between impaired cognitive control and enhanced automatic responsivity to rewarding food cues as key risk factors. The current study assessed the influence of four different components of trait impulsivity (reflecting impaired cognitive control) and automatic approach bias for food (reflecting automatic responsivity to food) on uncontrolled eating in a large sample (N = 504) of young adolescents. Of the four impulsivity factors, negative urgency was found to be the strongest predictor of uncontrolled eating. Interestingly, we found that lack of premeditation was a key risk factor for uncontrolled eating, but only when approach bias for food was high, supporting a dual-process model. Lack of perseverance showed a similar interactive pattern to a lesser degree and sensation-seeking did not predict uncontrolled eating. Together, our results show that distinct components of trait impulsivity are differentially associated with uncontrolled eating behaviour in adolescents, and that automatic processing of food cues may be an important factor in modulating this relationship. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Actinobacillus succinogenes ATCC 55618 Fermentation Medium Optimization for the Production of Succinic Acid by Response Surface Methodology

    PubMed Central

    Zhu, Li-Wen; Wang, Cheng-Cheng; Liu, Rui-Sang; Li, Hong-Mei; Wan, Duan-Ji; Tang, Ya-Jie

    2012-01-01

    As a potential intermediary feedstock, succinic acid takes an important place in bulk chemical productions. For the first time, a method combining Plackett-Burman design (PBD), steepest ascent method (SA), and Box-Behnken design (BBD) was developed to optimize Actinobacillus succinogenes ATCC 55618 fermentation medium. First, glucose, yeast extract, and MgCO3 were identified to be key medium components by PBD. Second, preliminary optimization was run by SA method to access the optimal region of the key medium components. Finally, the responses, that is, the production of succinic acid, were optimized simultaneously by using BBD, and the optimal concentration was located to be 84.6 g L−1 of glucose, 14.5 g L−1 of yeast extract, and 64.7 g L−1 of MgCO3. Verification experiment indicated that the maximal succinic acid production of 52.7 ± 0.8 g L−1 was obtained under the identified optimal conditions. The result agreed with the predicted value well. Compared with that of the basic medium, the production of succinic acid and yield of succinic acid against glucose were enhanced by 67.3% and 111.1%, respectively. The results obtained in this study may be useful for the industrial commercial production of succinic acid. PMID:23093852

  10. The role of the cell wall in fungal pathogenesis

    PubMed Central

    Arana, David M.; Prieto, Daniel; Román, Elvira; Nombela, César; Alonso‐Monge, Rebeca; Pla, Jesús

    2009-01-01

    Summary Fungal infections are a serious health problem. In recent years, basic research is focusing on the identification of fungal virulence factors as promising targets for the development of novel antifungals. The wall, as the most external cellular component, plays a crucial role in the interaction with host cells mediating processes such as adhesion or phagocytosis that are essential during infection. Specific components of the cell wall (called PAMPs) interact with specific receptors in the immune cell (called PRRs), triggering responses whose molecular mechanisms are being elucidated. We review here the main structural carbohydrate components of the fungal wall (glucan, mannan and chitin), how their biogenesis takes place in fungi and the specific receptors that they interact with. Different model fungal pathogens are chosen to illustrate the functional consequences of this interaction. Finally, the identification of the key components will have important consequences in the future and will allow better approaches to treat fungal infections. PMID:21261926

  11. The power of the placebo.

    PubMed

    Eccles, Ron

    2007-05-01

    The placebo is much more than a control medicine in a clinical trial. The placebo response is the largest component of any allergy treatment and consists of two components: nonspecific effects (eg, natural recovery) and a "true placebo effect" that is the psychological therapeutic effect of the treatment. Belief in the beneficial nature of the treatment is a key component of the true placebo effect, and can be enhanced by factors such as interaction with the physician and the sensory impact of the treatment. Negative beliefs can generate a nocebo effect that may explain some psychogenic illnesses; this is the basis of much research in psychoneuroimmunology. An understanding of the placebo and nocebo effects is important for general allergy practice, and harnessing the power of the true placebo effect is a major challenge to modern medicine.

  12. Roles and responsibilities of the nursing scholar.

    PubMed

    Conard, Patricia L; Pape, Tess Theresa

    2014-01-01

    Scholarship is an important facet of the nursing profession. There are many components, virtues, and roles and responsibilities of a nursing scholar practicing in today's ever-changing health care environment. Scholarship was redefined by Boyer to include scholarly activities in addition to research. Boyer's Model of Scholarship includes four interrelated and overlapping domains of discovery, integration, application, and teaching. Each domain is explained with examples for the pediatric nurse scholar, which includes roles in academia as well as in the practice setting. Pediatric nurses are key to scholarship in nursing because they work to improve the care of children.

  13. Effects of "D"-Amphetamine and Ethanol on Variable and Repetitive Key-Peck Sequences in Pigeons

    ERIC Educational Resources Information Center

    Ward, Ryan D.; Bailey, Ericka M.; Odum, Amy L.

    2006-01-01

    This experiment assessed the effects of "d"-Amphetamine and ethanol on reinforced variable and repetitive key-peck sequences in pigeons. Pigeons responded on two keys under a multiple schedule of Repeat and Vary components. In the Repeat component, completion of a target sequence of right, right, left, left resulted in food. In the Vary component,…

  14. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke.

    PubMed

    Nolan, Jerry P; Neumar, Robert W; Adrie, Christophe; Aibiki, Mayuki; Berg, Robert A; Böttiger, Bernd W; Callaway, Clifton; Clark, Robert S B; Geocadin, Romergryko G; Jauch, Edward C; Kern, Karl B; Laurent, Ivan; Longstreth, W T; Merchant, Raina M; Morley, Peter; Morrison, Laurie J; Nadkarni, Vinay; Peberdy, Mary Ann; Rivers, Emanuel P; Rodriguez-Nunez, Antonio; Sellke, Frank W; Spaulding, Christian; Sunde, Kjetil; Hoek, Terry Vanden

    2008-12-01

    To review the epidemiology, pathophysiology, treatment and prognostication in relation to the post-cardiac arrest syndrome. Relevant articles were identified using PubMed, EMBASE and an American Heart Association EndNote master resuscitation reference library, supplemented by hand searches of key papers. Writing groups comprising international experts were assigned to each section. Drafts of the document were circulated to all authors for comment and amendment. The 4 key components of post-cardiac arrest syndrome were identified as (1) post-cardiac arrest brain injury, (2) post-cardiac arrest myocardial dysfunction, (3) systemic ischaemia/reperfusion response, and (4) persistent precipitating pathology. A growing body of knowledge suggests that the individual components of the post-cardiac arrest syndrome are potentially treatable.

  15. The bioactive acidic serine- and aspartate-rich motif peptide.

    PubMed

    Minamizaki, Tomoko; Yoshiko, Yuji

    2015-01-01

    The organic component of the bone matrix comprises 40% dry weight of bone. The organic component is mostly composed of type I collagen and small amounts of non-collagenous proteins (NCPs) (10-15% of the total bone protein content). The small integrin-binding ligand N-linked glycoprotein (SIBLING) family, a NCP, is considered to play a key role in bone mineralization. SIBLING family of proteins share common structural features and includes the arginine-glycine-aspartic acid (RGD) motif and acidic serine- and aspartic acid-rich motif (ASARM). Clinical manifestations of gene mutations and/or genetically modified mice indicate that SIBLINGs play diverse roles in bone and extraskeletal tissues. ASARM peptides might not be primary responsible for the functional diversity of SIBLINGs, but this motif is suggested to be a key domain of SIBLINGs. However, the exact function of ASARM peptides is poorly understood. In this article, we discuss the considerable progress made in understanding the role of ASARM as a bioactive peptide.

  16. Women are More Sensitive than Men to Prior Trial Events on the Stop Signal Task

    PubMed Central

    Thakkar, Katharine N.; Congdon, Eliza; Poldrack, Russell A.; Sabb, Fred W.; London, Edythe D.; Cannon, Tyrone D.; Bilder, Robert M.

    2013-01-01

    Sexual dimorphism in the brain and cognition is a topic of widespread interest. Many studies of sex differences have focused on visuospatial and verbal abilities but few studies have investigated sex differences in executive functions. We examined two key components of executive function—response inhibition and response monitoring—in healthy men (n=285) and women (n=346) performing the Stop-signal task. In this task, participants are required to make a key press to a stimulus, unless a tone is presented at some delay following the initial stimulus presentation; on these infrequent trials, participants are instructed to inhibit their planned response. Response inhibition was assessed with an estimate of the latency needed to inhibit a response (stop-signal reaction time), and response monitoring was measured by calculating the degree to which participants adjusted their reaction times based on the immediately preceding trial (e.g. speeding following correct trials and slowing following errors). There were no sex differences in overall accuracy or response inhibition but women showed greater sensitivity to trial history. Women sped up more than men following correct “Go” trials, and slowed down more than men following errors. These small but statistically significant effects (Cohen’s d=0.25–0.3) suggest more flexible adjustments in speed-accuracy trade-offs in women and greater cognitive flexibility associated with the responsive control of action. PMID:24754812

  17. 7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys.

    PubMed Central

    Thompson, D M; Guidotti, A; DiBella, M; Costa, E

    1995-01-01

    We report here on the ability of IDRA 21 and aniracetam, two negative allosteric modulators of glutamate-induced DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor desensitization, to attenuate alprazolam-induced learning deficit in patas monkeys working in a complex behavioral task. In one component of a multiple schedule (repeated acquisition or "learning"), patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four discriminative stimuli (geometric forms or numerals). In the other component (performance) the four-response chain was the same each session. The response chain in each component was maintained by food presentation under a fixed-ratio schedule. When alprazolam (0.1 or 0.32 mg/kg p.o.) was administered alone, this full allosteric modulator of gamma-aminobutyric acid type A (GABAA) receptors produced large decreases in the response rate and accuracy in the learning component of the task. IDRA 21 (3 or 5.6 mg/kg p.o.) and aniracetam (30 mg/kg p.o.) administered 60 min before alprazolam, having no effect when given alone, antagonized the large disruptive effects of alprazolam on learning. From dose-response studies, it can be estimated that IDRA 21 is approximately 10-fold more potent than aniracetam in antagonizing alprazolam-induced learning deficit. We conclude that IDRA 21, a chemically unrelated pharmacological congener of aniracetam, improves learning deficit induced in patas monkeys by the increase of GABAergic tone elicited by alprazolam. Very likely IDRA 21 exerts its behavioral effects by antagonizing AMPA receptor desensitization. PMID:7644474

  18. 7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys.

    PubMed

    Thompson, D M; Guidotti, A; DiBella, M; Costa, E

    1995-08-15

    We report here on the ability of IDRA 21 and aniracetam, two negative allosteric modulators of glutamate-induced DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor desensitization, to attenuate alprazolam-induced learning deficit in patas monkeys working in a complex behavioral task. In one component of a multiple schedule (repeated acquisition or "learning"), patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four discriminative stimuli (geometric forms or numerals). In the other component (performance) the four-response chain was the same each session. The response chain in each component was maintained by food presentation under a fixed-ratio schedule. When alprazolam (0.1 or 0.32 mg/kg p.o.) was administered alone, this full allosteric modulator of gamma-aminobutyric acid type A (GABAA) receptors produced large decreases in the response rate and accuracy in the learning component of the task. IDRA 21 (3 or 5.6 mg/kg p.o.) and aniracetam (30 mg/kg p.o.) administered 60 min before alprazolam, having no effect when given alone, antagonized the large disruptive effects of alprazolam on learning. From dose-response studies, it can be estimated that IDRA 21 is approximately 10-fold more potent than aniracetam in antagonizing alprazolam-induced learning deficit. We conclude that IDRA 21, a chemically unrelated pharmacological congener of aniracetam, improves learning deficit induced in patas monkeys by the increase of GABAergic tone elicited by alprazolam. Very likely IDRA 21 exerts its behavioral effects by antagonizing AMPA receptor desensitization.

  19. Construction and analysis of a modular model of caspase activation in apoptosis

    PubMed Central

    Harrington, Heather A; Ho, Kenneth L; Ghosh, Samik; Tung, KC

    2008-01-01

    Background A key physiological mechanism employed by multicellular organisms is apoptosis, or programmed cell death. Apoptosis is triggered by the activation of caspases in response to both extracellular (extrinsic) and intracellular (intrinsic) signals. The extrinsic and intrinsic pathways are characterized by the formation of the death-inducing signaling complex (DISC) and the apoptosome, respectively; both the DISC and the apoptosome are oligomers with complex formation dynamics. Additionally, the extrinsic and intrinsic pathways are coupled through the mitochondrial apoptosis-induced channel via the Bcl-2 family of proteins. Results A model of caspase activation is constructed and analyzed. The apoptosis signaling network is simplified through modularization methodologies and equilibrium abstractions for three functional modules. The mathematical model is composed of a system of ordinary differential equations which is numerically solved. Multiple linear regression analysis investigates the role of each module and reduced models are constructed to identify key contributions of the extrinsic and intrinsic pathways in triggering apoptosis for different cell lines. Conclusion Through linear regression techniques, we identified the feedbacks, dissociation of complexes, and negative regulators as the key components in apoptosis. The analysis and reduced models for our model formulation reveal that the chosen cell lines predominately exhibit strong extrinsic caspase, typical of type I cell, behavior. Furthermore, under the simplified model framework, the selected cells lines exhibit different modes by which caspase activation may occur. Finally the proposed modularized model of apoptosis may generalize behavior for additional cells and tissues, specifically identifying and predicting components responsible for the transition from type I to type II cell behavior. PMID:19077196

  20. Phosphoinositide 3-kinase (PI3K(p110alpha)) directly regulates key components of the Z-disc and cardiac structure.

    PubMed

    Waardenberg, Ashley J; Bernardo, Bianca C; Ng, Dominic C H; Shepherd, Peter R; Cemerlang, Nelly; Sbroggiò, Mauro; Wells, Christine A; Dalrymple, Brian P; Brancaccio, Mara; Lin, Ruby C Y; McMullen, Julie R

    2011-09-02

    Maintenance of cardiac structure and Z-disc signaling are key factors responsible for protecting the heart in a setting of stress, but how these processes are regulated is not well defined. We recently demonstrated that PI3K(p110α) protects the heart against myocardial infarction. The aim of this study was to determine whether PI3K(p110α) directly regulates components of the Z-disc and cardiac structure. To address this question, a unique three-dimensional virtual muscle model was applied to gene expression data from transgenic mice with increased or decreased PI3K(p110α) activity under basal conditions (sham) and in a setting of myocardial infarction to display the location of structural proteins. Key findings from this analysis were then validated experimentally. The three-dimensional virtual muscle model visually highlighted reciprocally regulated transcripts associated with PI3K activation that encoded key components of the Z-disc and costamere, including melusin. Studies were performed to assess whether PI3K and melusin interact in the heart. Here, we identify a novel melusin-PI3K interaction that generates lipid kinase activity. The direct impact of PI3K(p110α) on myocyte structure was assessed by treating neonatal rat ventricular myocytes with PI3K(p110α) inhibitors and examining the myofiber morphology of hearts from PI3K transgenic mice. Results demonstrate that PI3K is critical for myofiber maturation and Z-disc alignment. In summary, PI3K regulates the expression of genes essential for cardiac structure and Z-disc signaling, interacts with melusin, and is critical for Z-disc alignment.

  1. Phosphoinositide 3-Kinase (PI3K(p110α)) Directly Regulates Key Components of the Z-disc and Cardiac Structure*

    PubMed Central

    Waardenberg, Ashley J.; Bernardo, Bianca C.; Ng, Dominic C. H.; Shepherd, Peter R.; Cemerlang, Nelly; Sbroggiò, Mauro; Wells, Christine A.; Dalrymple, Brian P.; Brancaccio, Mara; Lin, Ruby C. Y.; McMullen, Julie R.

    2011-01-01

    Maintenance of cardiac structure and Z-disc signaling are key factors responsible for protecting the heart in a setting of stress, but how these processes are regulated is not well defined. We recently demonstrated that PI3K(p110α) protects the heart against myocardial infarction. The aim of this study was to determine whether PI3K(p110α) directly regulates components of the Z-disc and cardiac structure. To address this question, a unique three-dimensional virtual muscle model was applied to gene expression data from transgenic mice with increased or decreased PI3K(p110α) activity under basal conditions (sham) and in a setting of myocardial infarction to display the location of structural proteins. Key findings from this analysis were then validated experimentally. The three-dimensional virtual muscle model visually highlighted reciprocally regulated transcripts associated with PI3K activation that encoded key components of the Z-disc and costamere, including melusin. Studies were performed to assess whether PI3K and melusin interact in the heart. Here, we identify a novel melusin-PI3K interaction that generates lipid kinase activity. The direct impact of PI3K(p110α) on myocyte structure was assessed by treating neonatal rat ventricular myocytes with PI3K(p110α) inhibitors and examining the myofiber morphology of hearts from PI3K transgenic mice. Results demonstrate that PI3K is critical for myofiber maturation and Z-disc alignment. In summary, PI3K regulates the expression of genes essential for cardiac structure and Z-disc signaling, interacts with melusin, and is critical for Z-disc alignment. PMID:21757757

  2. Eosinophils Regulate Interferon Alpha Production in Plasmacytoid Dendritic Cells Stimulated with Components of Neutrophil Extracellular Traps.

    PubMed

    Skrzeczynska-Moncznik, Joanna; Zabieglo, Katarzyna; Bossowski, Jozef P; Osiecka, Oktawia; Wlodarczyk, Agnieszka; Kapinska-Mrowiecka, Monika; Kwitniewski, Mateusz; Majewski, Pawel; Dubin, Adam; Cichy, Joanna

    2017-03-01

    Eosinophils constitute an important component of helminth immunity and are not only associated with various allergies but are also linked to autoinflammatory disorders, including the skin disease psoriasis. Here we demonstrate the functional relationship between eosinophils and plasmacytoid dendritic cells (pDCs) as related to skin diseases. We previously showed that pDCs colocalize with neutrophil extracellular traps (NETs) in psoriatic skin. Here we demonstrate that eosinophils are found in psoriatic skin near neutrophils and NETs, suggesting that pDC responses can be regulated by eosinophils. Eosinophils inhibited pDC function in vitro through a mechanism that did not involve cell contact but depended on soluble factors. In pDCs stimulated by specific NET components, eosinophil-conditioned media attenuated the production of interferon α (IFNα) but did not affect the maturation of pDCs as evidenced by the unaltered expression of the costimulatory molecules CD80 and CD86. As pDCs and IFNα play a key role in autoimmune skin inflammation, these data suggest that eosinophils may influence autoinflammatory responses through their impact on the production of IFNα by pDCs.

  3. Components of a comprehensive capital equipment planning program.

    PubMed

    Gresch, Alan

    2010-01-01

    As you may have already figured out, there is crossover and gaps between all of these capital equipment components. CE often will, and proactively should, make recommendations based on the CE, clinical, and financial components but rarely has direct knowledge of the strategic element. The clinical, finance, and administrative folks likely have visibility to most of these, but may lack full awareness of at least one component. The key is to engage key stakeholders from all these critical areas and develop a process to pull all this information together in one nice, neat package. Defining the person or persons responsible for taking the lead on this in your organization will depend greatly on the organization's type and size. For a single, standalone community hospital, it will likely be the facility administrator. For an integrated delivery network (IDN), a corporate entity, led by supply chain, finance, or both, may take the lead. Your organization may also employ consultative services or software to help facilitate this function. Regardless of who takes the lead, a weighting or scoring system that assigns certain values in all the outlined component categories, is clearly defined, and is easy to understand for all the contributors will need to be developed. If you are unaware or unclear of what the process is, find out and figure out how you can be a vital contributor to the process. This is one more way you can demonstrate the value you and your department bring to your organization.

  4. Responsible gambling: general principles and minimal requirements.

    PubMed

    Blaszczynski, Alex; Collins, Peter; Fong, Davis; Ladouceur, Robert; Nower, Lia; Shaffer, Howard J; Tavares, Hermano; Venisse, Jean-Luc

    2011-12-01

    Many international jurisdictions have introduced responsible gambling programs. These programs intend to minimize negative consequences of excessive gambling, but vary considerably in their aims, focus, and content. Many responsible gambling programs lack a conceptual framework and, in the absence of empirical data, their components are based only on general considerations and impressions. This paper outlines the consensus viewpoint of an international group of researchers suggesting fundamental responsible gambling principles, roles of key stakeholders, and minimal requirements that stakeholders can use to frame and inform responsible gambling programs across jurisdictions. Such a framework does not purport to offer value statements regarding the legal status of gambling or its expansion. Rather, it proposes gambling-related initiatives aimed at government, industry, and individuals to promote responsible gambling and consumer protection. This paper argues that there is a set of basic principles and minimal requirements that should form the basis for every responsible gambling program.

  5. Immune Priming, Fat Reserves, Muscle Mass and Body Weight of the House Cricket is Affected by Diet Composition.

    PubMed

    Córdoba-Aguilar, A; Nava-Sánchez, A; González-Tokman, D M; Munguía-Steyer, R; Gutiérrez-Cabrera, A E

    2016-08-01

    Some insect species are capable of producing an enhanced immune response after a first pathogenic encounter, a process called immune priming. However, whether and how such ability is driven by particular diet components (protein/carbohydrate) have not been explored. Such questions are sound given that, in general, immune response is dietary dependent. We have used adults of the house cricket Acheta domesticus L. (Orthoptera: Gryllidae) and exposed them to the bacteria Serratia marcescens. We first addressed whether survival rate after priming and nonpriming treatments is dietary dependent based on access/no access to proteins and carbohydrates. Second, we investigated how these dietary components affected fat reserves, muscle mass, and body weight, three key traits in insect fitness. Thus, we exposed adult house crickets to either a protein or a carbohydrate diet and measured the three traits. After being provided with protein, primed animals survived longer compared to the other diet treatments. Interestingly, this effect was also sex dependent with primed males having a higher survival than primed females when protein was supplemented. For the second experiment, protein-fed animals had more fat, muscle mass, and body weight than carbohydrate-fed animals. Although we are not aware of the immune component underlying immune priming, our results suggest that its energetic demand for its functioning and/or consequent survival requires a higher demand of protein with respect to carbohydrate. Thus, protein shortage can impair key survival-related traits related to immune and energetic condition. Further studies varying nutrient ratios should verify our results.

  6. Bombyx mori and Aedes aegypti form multi-functional immune complexes that integrate pattern recognition, melanization, coagulants, and hemocyte recruitment

    PubMed Central

    Phillips, Dennis R.

    2017-01-01

    The innate immune system of insects responds to wounding and pathogens by mobilizing multiple pathways that provide both systemic and localized protection. Key localized responses in hemolymph include melanization, coagulation, and hemocyte encapsulation, which synergistically seal wounds and envelop and destroy pathogens. To be effective, these pathways require a targeted deposition of their components to provide protection without compromising the host. Extensive research has identified a large number of the effectors that comprise these responses, but questions remain regarding their post-translational processing, function, and targeting. Here, we used mass spectrometry to demonstrate the integration of pathogen recognition proteins, coagulants, and melanization components into stable, high-mass, multi-functional Immune Complexes (ICs) in Bombyx mori and Aedes aegypti. Essential proteins common to both include phenoloxidases, apolipophorins, serine protease homologs, and a serine protease that promotes hemocyte recruitment through cytokine activation. Pattern recognition proteins included C-type Lectins in B. mori, while A. aegypti contained a protein homologous to Plasmodium-resistant LRIM1 from Anopheles gambiae. We also found that the B. mori IC is stabilized by extensive transglutaminase-catalyzed cross-linking of multiple components. The melanization inhibitor Egf1.0, from the parasitoid wasp Microplitis demolitor, blocked inclusion of specific components into the IC and also inhibited transglutaminase activity. Our results show how coagulants, melanization components, and hemocytes can be recruited to a wound surface or pathogen, provide insight into the mechanism by which a parasitoid evades this immune response, and suggest that insects as diverse as Lepidoptera and Diptera utilize similar defensive mechanisms. PMID:28199361

  7. Bombyx mori and Aedes aegypti form multi-functional immune complexes that integrate pattern recognition, melanization, coagulants, and hemocyte recruitment.

    PubMed

    Phillips, Dennis R; Clark, Kevin D

    2017-01-01

    The innate immune system of insects responds to wounding and pathogens by mobilizing multiple pathways that provide both systemic and localized protection. Key localized responses in hemolymph include melanization, coagulation, and hemocyte encapsulation, which synergistically seal wounds and envelop and destroy pathogens. To be effective, these pathways require a targeted deposition of their components to provide protection without compromising the host. Extensive research has identified a large number of the effectors that comprise these responses, but questions remain regarding their post-translational processing, function, and targeting. Here, we used mass spectrometry to demonstrate the integration of pathogen recognition proteins, coagulants, and melanization components into stable, high-mass, multi-functional Immune Complexes (ICs) in Bombyx mori and Aedes aegypti. Essential proteins common to both include phenoloxidases, apolipophorins, serine protease homologs, and a serine protease that promotes hemocyte recruitment through cytokine activation. Pattern recognition proteins included C-type Lectins in B. mori, while A. aegypti contained a protein homologous to Plasmodium-resistant LRIM1 from Anopheles gambiae. We also found that the B. mori IC is stabilized by extensive transglutaminase-catalyzed cross-linking of multiple components. The melanization inhibitor Egf1.0, from the parasitoid wasp Microplitis demolitor, blocked inclusion of specific components into the IC and also inhibited transglutaminase activity. Our results show how coagulants, melanization components, and hemocytes can be recruited to a wound surface or pathogen, provide insight into the mechanism by which a parasitoid evades this immune response, and suggest that insects as diverse as Lepidoptera and Diptera utilize similar defensive mechanisms.

  8. KatG, the Bifunctional Catalase of Xanthomonas citri subsp. citri, Responds to Hydrogen Peroxide and Contributes to Epiphytic Survival on Citrus Leaves.

    PubMed

    Tondo, María Laura; Delprato, María Laura; Kraiselburd, Ivana; Fernández Zenoff, María Verónica; Farías, María Eugenia; Orellano, Elena G

    2016-01-01

    Xanthomonas citri subsp. citri (Xcc) is the bacterium responsible for citrus canker. This bacterium is exposed to reactive oxygen species (ROS) at different points during its life cycle, including those normally produced by aerobic respiration or upon exposition to ultraviolet (UV) radiation. Moreover, ROS are key components of the host immune response. Among enzymatic ROS-detoxifying mechanisms, catalases eliminate H2O2, avoiding the potential damage caused by this specie. Xcc genome includes four catalase genes. In this work, we studied the physiological role of KatG, the only bifunctional catalase of Xcc, through the construction and characterization of a modified strain (XcckatG), carrying an insertional mutation in the katG gene. First, we evaluated the involvement of KatG in the bacterial adaptive response to H2O2. XcckatG cultures exhibited lower catalase activity than those of the wild-type strain, and this activity was not induced upon treatment with sub-lethal doses of H2O2. Moreover, the KatG-deficient mutant exhibited decreased tolerance to H2O2 toxicity compared to wild-type cells and accumulated high intracellular levels of peroxides upon exposure to sub-lethal concentrations of H2O2. To further study the role of KatG in Xcc physiology, we evaluated bacterial survival upon exposure to UV-A or UV-B radiation. In both conditions, XcckatG showed a high mortality in comparison to Xcc wild-type. Finally, we studied the development of bacterial biofilms. While structured biofilms were observed for the Xcc wild-type, the development of these structures was impaired for XcckatG. Based on these results, we demonstrated that KatG is responsible for Xcc adaptive response to H2O2 and a key component of the bacterial response to oxidative stress. Moreover, this enzyme plays an important role during Xcc epiphytic survival, being essential for biofilm formation and UV resistance.

  9. KatG, the Bifunctional Catalase of Xanthomonas citri subsp. citri, Responds to Hydrogen Peroxide and Contributes to Epiphytic Survival on Citrus Leaves

    PubMed Central

    Tondo, María Laura; Delprato, María Laura; Kraiselburd, Ivana; Fernández Zenoff, María Verónica; Farías, María Eugenia; Orellano, Elena G.

    2016-01-01

    Xanthomonas citri subsp. citri (Xcc) is the bacterium responsible for citrus canker. This bacterium is exposed to reactive oxygen species (ROS) at different points during its life cycle, including those normally produced by aerobic respiration or upon exposition to ultraviolet (UV) radiation. Moreover, ROS are key components of the host immune response. Among enzymatic ROS-detoxifying mechanisms, catalases eliminate H2O2, avoiding the potential damage caused by this specie. Xcc genome includes four catalase genes. In this work, we studied the physiological role of KatG, the only bifunctional catalase of Xcc, through the construction and characterization of a modified strain (XcckatG), carrying an insertional mutation in the katG gene. First, we evaluated the involvement of KatG in the bacterial adaptive response to H2O2. XcckatG cultures exhibited lower catalase activity than those of the wild-type strain, and this activity was not induced upon treatment with sub-lethal doses of H2O2. Moreover, the KatG-deficient mutant exhibited decreased tolerance to H2O2 toxicity compared to wild-type cells and accumulated high intracellular levels of peroxides upon exposure to sub-lethal concentrations of H2O2. To further study the role of KatG in Xcc physiology, we evaluated bacterial survival upon exposure to UV-A or UV-B radiation. In both conditions, XcckatG showed a high mortality in comparison to Xcc wild-type. Finally, we studied the development of bacterial biofilms. While structured biofilms were observed for the Xcc wild-type, the development of these structures was impaired for XcckatG. Based on these results, we demonstrated that KatG is responsible for Xcc adaptive response to H2O2 and a key component of the bacterial response to oxidative stress. Moreover, this enzyme plays an important role during Xcc epiphytic survival, being essential for biofilm formation and UV resistance. PMID:26990197

  10. Sensitivity studies of pediatric material properties on juvenile lumbar spine responses using finite element analysis.

    PubMed

    Jebaseelan, D Davidson; Jebaraj, C; Yoganandan, Narayan; Rajasekaran, S; Kanna, Rishi M

    2012-05-01

    The objective of the study was to determine the sensitivity of material properties of the juvenile spine to its external and internal responses using a finite element model under compression, and flexion-extension bending moments. The methodology included exercising the 8-year-old juvenile lumbar spine using parametric procedures. The model included the vertebral centrum, growth plates, laminae, pedicles, transverse processes and spinous processes; disc annulus and nucleus; and various ligaments. The sensitivity analysis was conducted by varying the modulus of elasticity for various components. The first simulation was done using mean material properties. Additional simulations were done for each component corresponding to low and high material property variations. External displacement/rotation and internal stress-strain responses were determined under compression and flexion-extension bending. Results indicated that, under compression, disc properties were more sensitive than bone properties, implying an elevated role of the disc under this mode. Under flexion-extension moments, ligament properties were more dominant than the other components, suggesting that various ligaments of the juvenile spine play a key role in modulating bending behaviors. Changes in the growth plate stress associated with ligament properties explained the importance of the growth plate in the pediatric spine with potential implications in progressive deformities.

  11. Mid-frequency Band Dynamics of Large Space Structures

    NASA Technical Reports Server (NTRS)

    Coppolino, Robert N.; Adams, Douglas S.

    2004-01-01

    High and low intensity dynamic environments experienced by a spacecraft during launch and on-orbit operations, respectively, induce structural loads and motions, which are difficult to reliably predict. Structural dynamics in low- and mid-frequency bands are sensitive to component interface uncertainty and non-linearity as evidenced in laboratory testing and flight operations. Analytical tools for prediction of linear system response are not necessarily adequate for reliable prediction of mid-frequency band dynamics and analysis of measured laboratory and flight data. A new MATLAB toolbox, designed to address the key challenges of mid-frequency band dynamics, is introduced in this paper. Finite-element models of major subassemblies are defined following rational frequency-wavelength guidelines. For computational efficiency, these subassemblies are described as linear, component mode models. The complete structural system model is composed of component mode subassemblies and linear or non-linear joint descriptions. Computation and display of structural dynamic responses are accomplished employing well-established, stable numerical methods, modern signal processing procedures and descriptive graphical tools. Parametric sensitivity and Monte-Carlo based system identification tools are used to reconcile models with experimental data and investigate the effects of uncertainties. Models and dynamic responses are exported for employment in applications, such as detailed structural integrity and mechanical-optical-control performance analyses.

  12. Traversing the Links between Heavy Metal Stress and Plant Signaling

    PubMed Central

    Jalmi, Siddhi K.; Bhagat, Prakash K.; Verma, Deepanjali; Noryang, Stanzin; Tayyeba, Sumaira; Singh, Kirti; Sharma, Deepika; Sinha, Alok K.

    2018-01-01

    Plants confront multifarious environmental stresses widely divided into abiotic and biotic stresses, of which heavy metal stress represents one of the most damaging abiotic stresses. Heavy metals cause toxicity by targeting crucial molecules and vital processes in the plant cell. One of the approaches by which heavy metals act in plants is by over production of reactive oxygen species (ROS) either directly or indirectly. Plants act against such overdose of metal in the environment by boosting the defense responses like metal chelation, sequestration into vacuole, regulation of metal intake by transporters, and intensification of antioxidative mechanisms. This response shown by plants is the result of intricate signaling networks functioning in the cell in order to transmit the extracellular stimuli into an intracellular response. The crucial signaling components involved are calcium signaling, hormone signaling, and mitogen activated protein kinase (MAPK) signaling that are discussed in this review. Apart from signaling components other regulators like microRNAs and transcription factors also have a major contribution in regulating heavy metal stress. This review demonstrates the key role of MAPKs in synchronously controlling the other signaling components and regulators in metal stress. Further, attempts have been made to focus on metal transporters and chelators that are regulated by MAPK signaling. PMID:29459874

  13. Identification of host fruit volatiles from flowering dogwood (Cornus florida) attractive to dogwood-origin Rhagoletis pomonella flies.

    PubMed

    Nojima, Satoshi; Linn, Charles; Roelofs, Wendell

    2003-10-01

    Solid-phase microextraction and gas chromatography coupled with electroantennographic detection were used to identify volatiles from fruit of flowering dogwood, Cornus florida, as key attractants for Rhagoletis pomonella flies originating from dogwood fruit. A six-component blend containing ethyl acetate (54.9%), 3-methylbutan-1-ol (27.5%), isoamyl acetate (0.9%), dimethyl trisulfide (1.9%), 1-octen-3-ol (9.1%), and beta-caryophyllene (5.8%) was identified from flowering dogwood fruit that gave consistent EAD activity. In a flight tunnel assay there was no significant difference in the response of individual dogwood flies exhibiting upwind anemotactic flight to volatile extracts from dogwood fruit and the six-component synthetic mixture. Dogwood flies also displayed significantly greater levels of upwind flight to sources with the dogwood volatile blend than with previously identified volatile blends from domestic apple or hawthorn fruit. Selected subtraction assays showed that the three-component mixture of 3-methylbutan-1-ol, 1-octen-3-ol, and beta-caryophyllene elicited levels of upwind flight to the source equivalent to the six-component mixture. Our study adds to previous ones showing that populations of Rhagoletis pomonella flies infesting apple, hawthorn, and flowering dogwood fruit are attracted to unique mixtures of fruit volatiles, supporting the hypothesis that host fruit odors could be key traits in sympatric host shifts and establishing host fidelity within members of the Rhagoletis pomonella species complex.

  14. Reserve Component Logistics Responsibilities in the Total Force,

    DTIC Science & Technology

    1982-10-01

    It diferent from Report) 14. SUPPLEMENTARY NOTES Four Service-specific Working Notes are included as Appendices. 19. KEY WORDS (Continue on reverse...During the balance of the task, we will augment the data presented in this working note with: - time phasing of RC units after mobilization for a NATO or...aerial refueling During the balance of the task, we will augment the data presented in this working paper with: - time phasings of RC units after

  15. Estimating the Size and Components of the U.S. Child Care Workforce and Caregiving Population. Key Findings from the Child Care Workforce Estimate. Preliminary Report.

    ERIC Educational Resources Information Center

    Burton, Alice; Whitebook, Marcy; Young, Marci; Bellm, Dan; Wayne, Claudia; Brandon, Richard N.; Maher, Erin

    In response to rising demand for information on the child care workforce, the Center for the Child Care Workforce (CCW) and the Human Services Policy Center (HSPC) have initiated a 2-year project to develop a framework and methodology for quantifying the size and characteristics of the U.S. child care workforce, focusing on the workforce serving…

  16. Self-Initiated Development of Leadership Capabilities: Toward Establishing the Validity of Key Motivational Constructs and Assessment Tools

    DTIC Science & Technology

    2010-11-01

    such as pay increases, promotions, increases in leader- ship responsibility, leadership performance /behavior ratings, and satisfaction at work. The... Vroom , 1964), self-efficacy (or expectation that one will succeed at a task) is a sub-component or direct predictor of overall motivation to perform a... satisfaction . Comparing Motivation to Lead and Motivation to Develop Leadership in Predicting Leadership Performance and Career Success In this

  17. The National Disaster Medical System

    NASA Technical Reports Server (NTRS)

    Reutershan, Thomas P.

    1991-01-01

    The Emergency Mobilization Preparedness Board developed plans for improved national preparedness in case of major catastrophic domestic disaster or the possibility of an overseas conventional conflict. Within the health and medical arena, the working group on health developed the concept and system design for the National Disaster Medical System (NDMS). A description of NDMS is presented including the purpose, key components, medical response, patient evacuation, definitive medical care, NDMS activation and operations, and summary and benefits.

  18. SMG-1 and mTORC1 Act Antagonistically to Regulate Response to Injury and Growth in Planarians

    PubMed Central

    González-Estévez, Cristina; Felix, Daniel A.; Smith, Matthew D.; Paps, Jordi; Morley, Simon J.; James, Victoria; Sharp, Tyson V.; Aboobaker, A. Aziz

    2012-01-01

    Planarian flatworms are able to both regenerate their whole bodies and continuously adapt their size to nutrient status. Tight control of stem cell proliferation and differentiation during these processes is the key feature of planarian biology. Here we show that the planarian homolog of the phosphoinositide 3-kinase-related kinase (PIKK) family member SMG-1 and mTOR complex 1 components are required for this tight control. Loss of smg-1 results in a hyper-responsiveness to injury and growth and the formation of regenerative blastemas that remain undifferentiated and that lead to lethal ectopic outgrowths. Invasive stem cell hyper-proliferation, hyperplasia, hypertrophy, and differentiation defects are hallmarks of this uncontrolled growth. These data imply a previously unappreciated and novel physiological function for this PIKK family member. In contrast we found that planarian members of the mTOR complex 1, tor and raptor, are required for the initial response to injury and blastema formation. Double smg-1 RNAi experiments with tor or raptor show that abnormal growth requires mTOR signalling. We also found that the macrolide rapamycin, a natural compound inhibitor of mTORC1, is able to increase the survival rate of smg-1 RNAi animals by decreasing cell proliferation. Our findings support a model where Smg-1 acts as a novel regulator of both the response to injury and growth control mechanisms. Our data suggest the possibility that this may be by suppressing mTOR signalling. Characterisation of both the planarian mTORC1 signalling components and another PIKK family member as key regulators of regeneration and growth will influence future work on regeneration, growth control, and the development of anti-cancer therapies that target mTOR signalling. PMID:22479207

  19. Molecular analyses of the principal components of response strength.

    PubMed Central

    Killeen, Peter R; Hall, Scott S; Reilly, Mark P; Kettle, Lauren C

    2002-01-01

    Killeen and Hall (2001) showed that a common factor called strength underlies the key dependent variables of response probability, latency, and rate, and that overall response rate is a good predictor of strength. In a search for the mechanisms that underlie those correlations, this article shows that (a) the probability of responding on a trial is a two-state Markov process; (b) latency and rate of responding can be described in terms of the probability and period of stochastic machines called clocked Bernoulli modules, and (c) one such machine, the refractory Poisson process, provides a functional relation between the probability of observing a response during any epoch and the rate of responding. This relation is one of proportionality at low rates and curvilinearity at higher rates. PMID:12216975

  20. Phosphate Sink Containing Two-Component Signaling Systems as Tunable Threshold Devices

    PubMed Central

    Amin, Munia; Kothamachu, Varun B.; Feliu, Elisenda; Scharf, Birgit E.; Porter, Steven L.; Soyer, Orkun S.

    2014-01-01

    Synthetic biology aims to design de novo biological systems and reengineer existing ones. These efforts have mostly focused on transcriptional circuits, with reengineering of signaling circuits hampered by limited understanding of their systems dynamics and experimental challenges. Bacterial two-component signaling systems offer a rich diversity of sensory systems that are built around a core phosphotransfer reaction between histidine kinases and their output response regulator proteins, and thus are a good target for reengineering through synthetic biology. Here, we explore the signal-response relationship arising from a specific motif found in two-component signaling. In this motif, a single histidine kinase (HK) phosphotransfers reversibly to two separate output response regulator (RR) proteins. We show that, under the experimentally observed parameters from bacteria and yeast, this motif not only allows rapid signal termination, whereby one of the RRs acts as a phosphate sink towards the other RR (i.e. the output RR), but also implements a sigmoidal signal-response relationship. We identify two mathematical conditions on system parameters that are necessary for sigmoidal signal-response relationships and define key parameters that control threshold levels and sensitivity of the signal-response curve. We confirm these findings experimentally, by in vitro reconstitution of the one HK-two RR motif found in the Sinorhizobium meliloti chemotaxis pathway and measuring the resulting signal-response curve. We find that the level of sigmoidality in this system can be experimentally controlled by the presence of the sink RR, and also through an auxiliary protein that is shown to bind to the HK (yielding Hill coefficients of above 7). These findings show that the one HK-two RR motif allows bacteria and yeast to implement tunable switch-like signal processing and provides an ideal basis for developing threshold devices for synthetic biology applications. PMID:25357192

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

    Lai, Jih-Sheng

    This paper introduces control system design based softwares, SIMNON and MATLAB/SIMULINK, for power electronics system simulation. A complete power electronics system typically consists of a rectifier bridge along with its smoothing capacitor, an inverter, and a motor. The system components, featuring discrete or continuous, linear or nonlinear, are modeled in mathematical equations. Inverter control methods,such as pulse-width-modulation and hysteresis current control, are expressed in either computer algorithms or digital circuits. After describing component models and control methods, computer programs are then developed for complete systems simulation. Simulation results are mainly used for studying system performances, such as input and outputmore » current harmonics, torque ripples, and speed responses. Key computer programs and simulation results are demonstrated for educational purposes.« less

  2. Modeling Systems-Level Regulation of Host Immune Responses

    PubMed Central

    Thakar, Juilee; Pilione, Mylisa; Kirimanjeswara, Girish; Harvill, Eric T; Albert, Réka

    2007-01-01

    Many pathogens are able to manipulate the signaling pathways responsible for the generation of host immune responses. Here we examine and model a respiratory infection system in which disruption of host immune functions or of bacterial factors changes the dynamics of the infection. We synthesize the network of interactions between host immune components and two closely related bacteria in the genus Bordetellae. We incorporate existing experimental information on the timing of immune regulatory events into a discrete dynamic model, and verify the model by comparing the effects of simulated disruptions to the experimental outcome of knockout mutations. Our model indicates that the infection time course of both Bordetellae can be separated into three distinct phases based on the most active immune processes. We compare and discuss the effect of the species-specific virulence factors on disrupting the immune response during their infection of naive, antibody-treated, diseased, or convalescent hosts. Our model offers predictions regarding cytokine regulation, key immune components, and clearance of secondary infections; we experimentally validate two of these predictions. This type of modeling provides new insights into the virulence, pathogenesis, and host adaptation of disease-causing microorganisms and allows systems-level analysis that is not always possible using traditional methods. PMID:17559300

  3. Optimism and pessimism are related to different components of the stress response in healthy older people.

    PubMed

    Puig-Perez, Sara; Villada, Carolina; Pulopulos, Matias M; Almela, Mercedes; Hidalgo, Vanesa; Salvador, Alicia

    2015-11-01

    Some personality traits have key importance for health because they can affect the maintenance and evolution of different disorders with a high prevalence in older people, including stress pathologies and diseases. In this study we investigated how two relevant personality traits, optimism and pessimism, affect the psychophysiological response of 72 healthy participants (55 to 76 years old) exposed to either a psychosocial stress task (Trier Social Stress Test, TSST) or a control task; salivary cortisol, heart rate (HR) and situational appraisal were measured. Our results showed that optimism was related to faster cortisol recovery after exposure to stress. Pessimism was not related to the physiological stress response, but it was associated with the perception of the stress task as more difficult. Thus, higher optimism was associated with better physiological adjustment to a stressful situation, while higher pessimism was associated with worse psychological adjustment to stress. These results highlight different patterns of relationships, with optimism playing a more important role in the physiological component of the stress response, and pessimism having a greater effect on situational appraisal. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. WRKY transcription factors: key components in abscisic acid signalling.

    PubMed

    Rushton, Deena L; Tripathi, Prateek; Rabara, Roel C; Lin, Jun; Ringler, Patricia; Boken, Ashley K; Langum, Tanner J; Smidt, Lucas; Boomsma, Darius D; Emme, Nicholas J; Chen, Xianfeng; Finer, John J; Shen, Qingxi J; Rushton, Paul J

    2012-01-01

    WRKY transcription factors (TFs) are key regulators of many plant processes, including the responses to biotic and abiotic stresses, senescence, seed dormancy and seed germination. For over 15 years, limited evidence has been available suggesting that WRKY TFs may play roles in regulating plant responses to the phytohormone abscisic acid (ABA), notably some WRKY TFs are ABA-inducible repressors of seed germination. However, the roles of WRKY TFs in other aspects of ABA signalling, and the mechanisms involved, have remained unclear. Recent significant progress in ABA research has now placed specific WRKY TFs firmly in ABA-responsive signalling pathways, where they act at multiple levels. In Arabidopsis, WRKY TFs appear to act downstream of at least two ABA receptors: the cytoplasmic PYR/PYL/RCAR-protein phosphatase 2C-ABA complex and the chloroplast envelope-located ABAR-ABA complex. In vivo and in vitro promoter-binding studies show that the target genes for WRKY TFs that are involved in ABA signalling include well-known ABA-responsive genes such as ABF2, ABF4, ABI4, ABI5, MYB2, DREB1a, DREB2a and RAB18. Additional well-characterized stress-inducible genes such as RD29A and COR47 are also found in signalling pathways downstream of WRKY TFs. These new insights also reveal that some WRKY TFs are positive regulators of ABA-mediated stomatal closure and hence drought responses. Conversely, many WRKY TFs are negative regulators of seed germination, and controlling seed germination appears a common function of a subset of WRKY TFs in flowering plants. Taken together, these new data demonstrate that WRKY TFs are key nodes in ABA-responsive signalling networks. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  5. Role of α-crystallin B in regulation of stress induced cardiomyocyte apoptosis.

    PubMed

    Ganguly, Subhalakshmi; Mitra, Arkadeep; Sarkar, Sagartirtha

    2014-01-01

    Cardiovascular disease is the leading cause of death worldwide. Recently emerging evidence suggests that cardiomyocyte apoptosis is one of the major pathogenic factors in heart diseases leading to heart failure. Cardiomyocytes undergo apoptosis in response to a wide variety of cellular stresses including protein folding stress at Endoplasmic reticulum (ER). Stressed myocytes elicit an adaptive response referred as Unfolded Protein Response (UPR) by inducing accumulation of heat shock proteins (HSPs) to mitigate the ER stress. HSPs act as molecular chaperons by assisting correct folding of the aggregated misfolded proteins in ER lumen. α-Crystallin B (CRYAB) is an abundant small HSP that confers protection to cardiomyocytes against various stress stimuli. Recent evidence indicates that CRYAB directly interacts with several components of ER stress and also mitochondrial apoptotic pathway. Based on currently available literature this mini review will focus on how CRYAB confers protection to stressed myocardium thereby emphasizing its function as antiapoptotic molecule. Understanding the interplay between CRYAB and the key components in the apoptotic signaling cascade mediated by ER and mitochondria will help in development of novel therapies for cardiac diseases.

  6. Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues

    PubMed Central

    Zhang, Sharon; Ratliff, Eric P.; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W.; Achal, Madhulika; Mauntz, Ruth E.; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A.; Macias, Andrew M.; Daugherty, Daniel; Harris, Greg L.; Edwards, Robert A.; Finley, Kim D.

    2018-01-01

    The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system. PMID:29642630

  7. Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues.

    PubMed

    Zhang, Sharon; Ratliff, Eric P; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W; Achal, Madhulika; Mauntz, Ruth E; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A; Macias, Andrew M; Daugherty, Daniel; Harris, Greg L; Edwards, Robert A; Finley, Kim D

    2018-04-10

    The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system.

  8. The new ATLAS Fast Calorimeter Simulation

    NASA Astrophysics Data System (ADS)

    Schaarschmidt, J.; ATLAS Collaboration

    2017-10-01

    Current and future need for large scale simulated samples motivate the development of reliable fast simulation techniques. The new Fast Calorimeter Simulation is an improved parameterized response of single particles in the ATLAS calorimeter that aims to accurately emulate the key features of the detailed calorimeter response as simulated with Geant4, yet approximately ten times faster. Principal component analysis and machine learning techniques are used to improve the performance and decrease the memory need compared to the current version of the ATLAS Fast Calorimeter Simulation. A prototype of this new Fast Calorimeter Simulation is in development and its integration into the ATLAS simulation infrastructure is ongoing.

  9. GPS synchronized power system phase angle measurements

    NASA Astrophysics Data System (ADS)

    Wilson, Robert E.; Sterlina, Patrick S.

    1994-09-01

    This paper discusses the use of Global Positioning System (GPS) synchronized equipment for the measurement and analysis of key power system quantities. Two GPS synchronized phasor measurement units (PMU) were installed before testing. It was indicated that PMUs recorded the dynamic response of the power system phase angles when the northern California power grid was excited by the artificial short circuits. Power system planning engineers perform detailed computer generated simulations of the dynamic response of the power system to naturally occurring short circuits. The computer simulations use models of transmission lines, transformers, circuit breakers, and other high voltage components. This work will compare computer simulations of the same event with field measurement.

  10. miR-958 inhibits Toll signaling and Drosomycin expression via direct targeting of Toll and Dif in Drosophila melanogaster.

    PubMed

    Li, Shengjie; Li, Yao; Shen, Li; Jin, Ping; Chen, Liming; Ma, Fei

    2017-02-01

    Drosophila melanogaster is widely used as a model system to study innate immunity and signaling pathways related to innate immunity, including the Toll signaling pathway. Although this pathway is well studied, the precise mechanisms of posttranscriptional regulation of key components of the Toll signaling pathway by microRNAs (miRNAs) remain obscure. In this study, we used an in silico strategy in combination with the Gal80 ts -Gal4 driver system to identify microRNA-958 (miR-958) as a candidate Toll pathway regulating miRNA in Drosophila We report that overexpression of miR-958 significantly reduces the expression of Drosomycin, a key antimicrobial peptide involved in Toll signaling and the innate immune response. We further demonstrate in vitro and in vivo that miR-958 targets the Toll and Dif genes, key components of the Toll signaling pathway, to negatively regulate Drosomycin expression. In addition, a miR-958 sponge rescued the expression of Toll and Dif, resulting in increased expression of Drosomycin. These results, not only revealed a novel function and modulation pattern of miR-958, but also provided a new insight into the underlying molecular mechanisms of Toll signaling in regulation of innate immunity. Copyright © 2017 the American Physiological Society.

  11. Density and glass forming ability in amorphous atomic alloys: The role of the particle softness

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

    Douglass, Ian; Hudson, Toby; Harrowell, Peter

    A key property of glass forming alloys, the anomalously small volume difference with respect to the crystal, is shown to arise as a direct consequence of the soft repulsive potentials between metals. This feature of the inter-atomic potential is demonstrated to be responsible for a significant component of the glass forming ability of alloys due to the decrease in the enthalpy of fusion and the associated depression of the freezing point.

  12. Abscisic Acid (ABA) Regulation of Arabidopsis SR Protein Gene Expression

    PubMed Central

    Cruz, Tiago M. D.; Carvalho, Raquel F.; Richardson, Dale N.; Duque, Paula

    2014-01-01

    Serine/arginine-rich (SR) proteins are major modulators of alternative splicing, a key generator of proteomic diversity and flexible means of regulating gene expression likely to be crucial in plant environmental responses. Indeed, mounting evidence implicates splicing factors in signal transduction of the abscisic acid (ABA) phytohormone, which plays pivotal roles in the response to various abiotic stresses. Using real-time RT-qPCR, we analyzed total steady-state transcript levels of the 18 SR and two SR-like genes from Arabidopsis thaliana in seedlings treated with ABA and in genetic backgrounds with altered expression of the ABA-biosynthesis ABA2 and the ABA-signaling ABI1 and ABI4 genes. We also searched for ABA-responsive cis elements in the upstream regions of the 20 genes. We found that members of the plant-specific SC35-Like (SCL) Arabidopsis SR protein subfamily are distinctively responsive to exogenous ABA, while the expression of seven SR and SR-related genes is affected by alterations in key components of the ABA pathway. Finally, despite pervasiveness of established ABA-responsive promoter elements in Arabidopsis SR and SR-like genes, their expression is likely governed by additional, yet unidentified cis-acting elements. Overall, this study pinpoints SR34, SR34b, SCL30a, SCL28, SCL33, RS40, SR45 and SR45a as promising candidates for involvement in ABA-mediated stress responses. PMID:25268622

  13. Nitrate Transport, Sensing, and Responses in Plants.

    PubMed

    O'Brien, José A; Vega, Andrea; Bouguyon, Eléonore; Krouk, Gabriel; Gojon, Alain; Coruzzi, Gloria; Gutiérrez, Rodrigo A

    2016-06-06

    Nitrogen (N) is an essential macronutrient that affects plant growth and development. N is an important component of chlorophyll, amino acids, nucleic acids, and secondary metabolites. Nitrate is one of the most abundant N sources in the soil. Because nitrate and other N nutrients are often limiting, plants have developed sophisticated mechanisms to ensure adequate supply of nutrients in a variable environment. Nitrate is absorbed in the root and mobilized to other organs by nitrate transporters. Nitrate sensing activates signaling pathways that impinge upon molecular, metabolic, physiological, and developmental responses locally and at the whole plant level. With the advent of genomics technologies and genetic tools, important advances in our understanding of nitrate and other N nutrient responses have been achieved in the past decade. Furthermore, techniques that take advantage of natural polymorphisms present in divergent individuals from a single species have been essential in uncovering new components. However, there are still gaps in our understanding of how nitrate signaling affects biological processes in plants. Moreover, we still lack an integrated view of how all the regulatory factors identified interact or crosstalk to orchestrate the myriad N responses plants typically exhibit. In this review, we provide an updated overview of mechanisms by which nitrate is sensed and transported throughout the plant. We discuss signaling components and how nitrate sensing crosstalks with hormonal pathways for developmental responses locally and globally in the plant. Understanding how nitrate impacts on plant metabolism, physiology, and growth and development in plants is key to improving crops for sustainable agriculture. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

  14. Human Immunity and the Design of Multi-Component, Single Target Vaccines

    PubMed Central

    Saul, Allan; Fay, Michael P.

    2007-01-01

    Background Inclusion of multiple immunogens to target a single organism is a strategy being pursued for many experimental vaccines, especially where it is difficult to generate a strongly protective response from a single immunogen. Although there are many human vaccines that contain multiple defined immunogens, in almost every case each component targets a different pathogen. As a consequence, there is little practical experience for deciding where the increased complexity of vaccines with multiple defined immunogens vaccines targeting single pathogens will be justifiable. Methodology/Principal Findings A mathematical model, with immunogenicity parameters derived from a database of human responses to established vaccines, was used to predict the increase in the efficacy and the proportion of the population protected resulting from addition of further immunogens. The gains depended on the relative protection and the range of responses in the population to each immunogen and also to the correlation of the responses between immunogens. In most scenarios modeled, the gain in overall efficacy obtained by adding more immunogens was comparable to gains obtained from a single immunogen through the use of better formulations or adjuvants. Multi-component single target vaccines were more effective at decreasing the proportion of poor responders than increasing the overall efficacy of the vaccine in a population. Conclusions/Significance Inclusion of limited number of antigens in a vaccine aimed at targeting a single organism will increase efficacy, but the gains are relatively modest and for a practical vaccine there are constraints that are likely to limit multi-component single target vaccines to a small number of key antigens. The model predicts that this type of vaccine will be most useful where the critical issue is the reduction in proportion of poor responders. PMID:17786221

  15. A cognitive task analysis of information management strategies in a computerized provider order entry environment.

    PubMed

    Weir, Charlene R; Nebeker, Jonathan J R; Hicken, Bret L; Campo, Rebecca; Drews, Frank; Lebar, Beth

    2007-01-01

    Computerized Provider Order Entry (CPOE) with electronic documentation, and computerized decision support dramatically changes the information environment of the practicing clinician. Prior work patterns based on paper, verbal exchange, and manual methods are replaced with automated, computerized, and potentially less flexible systems. The objective of this study is to explore the information management strategies that clinicians use in the process of adapting to a CPOE system using cognitive task analysis techniques. Observation and semi-structured interviews were conducted with 88 primary-care clinicians at 10 Veterans Administration Medical Centers. Interviews were taped, transcribed, and extensively analyzed to identify key information management goals, strategies, and tasks. Tasks were aggregated into groups, common components across tasks were clarified, and underlying goals and strategies identified. Nearly half of the identified tasks were not fully supported by the available technology. Six core components of tasks were identified. Four meta-cognitive information management goals emerged: 1) Relevance Screening; 2) Ensuring Accuracy; 3) Minimizing memory load; and 4) Negotiating Responsibility. Strategies used to support these goals are presented. Users develop a wide array of information management strategies that allow them to successfully adapt to new technology. Supporting the ability of users to develop adaptive strategies to support meta-cognitive goals is a key component of a successful system.

  16. Modeling the frequency response of microwave radiometers with QUCS

    NASA Astrophysics Data System (ADS)

    Zonca, A.; Roucaries, B.; Williams, B.; Rubin, I.; D'Arcangelo, O.; Meinhold, P.; Lubin, P.; Franceschet, C.; Jahn, S.; Mennella, A.; Bersanelli, M.

    2010-12-01

    Characterization of the frequency response of coherent radiometric receivers is a key element in estimating the flux of astrophysical emissions, since the measured signal depends on the convolution of the source spectral emission with the instrument band shape. Laboratory Radio Frequency (RF) measurements of the instrument bandpass often require complex test setups and are subject to a number of systematic effects driven by thermal issues and impedance matching, particularly if cryogenic operation is involved. In this paper we present an approach to modeling radiometers bandpasses by integrating simulations and RF measurements of individual components. This method is based on QUCS (Quasi Universal Circuit Simulator), an open-source circuit simulator, which gives the flexibility of choosing among the available devices, implementing new analytical software models or using measured S-parameters. Therefore an independent estimate of the instrument bandpass is achieved using standard individual component measurements and validated analytical simulations. In order to automate the process of preparing input data, running simulations and exporting results we developed the Python package python-qucs and released it under GNU Public License. We discuss, as working cases, bandpass response modeling of the COFE and Planck Low Frequency Instrument (LFI) radiometers and compare results obtained with QUCS and with a commercial circuit simulator software. The main purpose of bandpass modeling in COFE is to optimize component matching, while in LFI they represent the best estimation of frequency response, since end-to-end measurements were strongly affected by systematic effects.

  17. [Specific odor component produced by Mycobacterium lepraemurium on Ogawa yolk medium].

    PubMed

    Mori, T; Aishima, T

    1992-11-01

    When Mycobacterium lepraemurium is grown on the 1% Ogawa yolk medium, it produces a specific odor. This odor was not observed in other easily cultivable acid-fast bacilli. Therefore, identification of the components responsible for the specific odor produced by M. lepraemurium was attempted. The odor components were extracted for overnight with sterilized and distilled water from the Ogawa yolk medium on which M. lepraemurium had been cultivated for two months. The odor components in the extract was adsorbed on refined charcoal. After washing with distilled water for three times, the charcoal was dried. Then the odor components were eluted from the charcoal with ethanol and the eluate was condensed under nitrogen gas flow at 40 degrees C. The condensate was analyzed by Gas-Chromatography-Mass-Spectrum (GC-MS). Phenylethanol and phenylacetic acid were identified as major odor components. A mixture of authentic phenylacetic acid, its methyl and ethyl esters, smelled similar to the odor of cultivated medium of M. lepraemurium. Thus, phenylacetic acid was identified as the key odor component produced by M. lepraemurium. When initial isolation culture of M. lepraemurium from murine leproma was cultivated on the Ogawa yolk medium by adding phenylacetic acid, growth inhibition was brought by the compound.

  18. Periodic components of hand acceleration/deceleration impulses during telemanipulation

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

    Draper, J.V.; Handel, S.

    1994-01-01

    Responsiveness is the ability of a telemanipulator to recreate user trajectories and impedance in time and space. For trajectory production, a key determinant of responsiveness is the ability of the system to accept user inputs, which are forces on the master handle generated by user hand acceleration/deceleration (a/d) impulses, and translate them into slave arm acceleration/deceleration. This paper presents observations of master controller a/d impulses during completion of a simple target acquisition task. Power spectral density functions (PSDF`s) calculated from hand controller a/d impulses were used to assess impulse waveform. The relative contributions of frequency intervals ranging up to 25more » Hz for three spatially different versions of the task were used to determine which frequencies were most important. The highest relative power was observed in frequencies between 1 Hz and 6 Hz. The key frequencies related to task difficulty were in the range from 2 Hz to 8 Hz. the results provide clues to the source of the performance inhibition.« less

  19. A Simple Model Framework to Explore the Deeply Uncertain, Local Sea Level Response to Climate Change. A Case Study on New Orleans, Louisiana

    NASA Astrophysics Data System (ADS)

    Bakker, Alexander; Louchard, Domitille; Keller, Klaus

    2016-04-01

    Sea-level rise threatens many coastal areas around the world. The integrated assessment of potential adaptation and mitigation strategies requires a sound understanding of the upper tails and the major drivers of the uncertainties. Global warming causes sea-level to rise, primarily due to thermal expansion of the oceans and mass loss of the major ice sheets, smaller ice caps and glaciers. These components show distinctly different responses to temperature changes with respect to response time, threshold behavior, and local fingerprints. Projections of these different components are deeply uncertain. Projected uncertainty ranges strongly depend on (necessary) pragmatic choices and assumptions; e.g. on the applied climate scenarios, which processes to include and how to parameterize them, and on error structure of the observations. Competing assumptions are very hard to objectively weigh. Hence, uncertainties of sea-level response are hard to grasp in a single distribution function. The deep uncertainty can be better understood by making clear the key assumptions. Here we demonstrate this approach using a relatively simple model framework. We present a mechanistically motivated, but simple model framework that is intended to efficiently explore the deeply uncertain sea-level response to anthropogenic climate change. The model consists of 'building blocks' that represent the major components of sea-level response and its uncertainties, including threshold behavior. The framework's simplicity enables the simulation of large ensembles allowing for an efficient exploration of parameter uncertainty and for the simulation of multiple combined adaptation and mitigation strategies. The model framework can skilfully reproduce earlier major sea level assessments, but due to the modular setup it can also be easily utilized to explore high-end scenarios and the effect of competing assumptions and parameterizations.

  20. HIV therapeutic vaccines: moving towards a functional cure.

    PubMed

    Mylvaganam, Geetha H; Silvestri, Guido; Amara, Rama Rao

    2015-08-01

    Anti-viral T-cell and B-cell responses play a crucial role in suppressing HIV and SIV replication during chronic infection. However, these infections are rarely controlled by the host immune response, and most infected individuals need lifelong antiretroviral therapy (ART). Recent advances in our understanding of how anti-HIV immune responses are elicited and regulated prompted a surge of interest in harnessing these responses to reduce the HIV 'residual disease' that is present in ART-treated HIV-infected individuals. Novel approaches that are currently explored include both conventional therapeutic vaccines (i.e., active immunization strategies using HIV-derived immunogens) as well as the use of checkpoint blockers such as anti-PD-1 antibodies. These approaches appear promising as key components of complex therapeutic strategies aimed at curing HIV infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. The influence of μ-opioid and noradrenaline reuptake inhibition in the modulation of pain responsive neurones in the central amygdala by tapentadol in rats with neuropathy

    PubMed Central

    Gonçalves, Leonor; Friend, Lauren V.; Dickenson, Anthony H.

    2015-01-01

    Treatments for neuropathic pain are either not fully effective or have problematic side effects. Combinations of drugs are often used. Tapentadol is a newer molecule that produces analgesia in various pain models through two inhibitory mechanisms, namely central μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. These two components interact synergistically, resulting in levels of analgesia similar to opioid analgesics such as oxycodone and morphine, but with more tolerable side effects. The right central nucleus of the amygdala (CeA) is critical for the lateral spinal ascending pain pathway, regulates descending pain pathways and is key in the emotional-affective components of pain. Few studies have investigated the pharmacology of limbic brain areas in pain models. Here we determined the actions of systemic tapentadol on right CeA neurones of animals with neuropathy and which component of tapentadol contributes to its effect. Neuronal responses to multimodal peripheral stimulation of animals with spinal nerve ligation or sham surgery were recorded before and after two doses of tapentadol. After the higher dose of tapentadol either naloxone or yohimbine were administered. Systemic tapentadol resulted in dose-dependent decrease in right CeA neuronal activity only in neuropathy. Both naloxone and yohimbine reversed this effect to an extent that was modality selective. The interactions of the components of tapentadol are not limited to the synergy between the MOR and α2-adrenoceptors seen at spinal levels, but are seen at this supraspinal site where suppression of responses may relate to the ability of the drug to alter affective components of pain. PMID:25576174

  2. A feasibility work on the applications of MRE to automotive components

    NASA Astrophysics Data System (ADS)

    Kim, S. H.; Park, Y. J.; Cha, A. R.; Kim, G. W.; Bang, J. H.; Lim, C. S.; Choi, S. B.

    2018-03-01

    A feasibility work on the application of magneto-rheological elastomers (MREs) to automotive components, such as engine mounts is presented. While vehicle components require the high resonance frequency in terms of ride quality and handling, it is required to have the low resonance frequency to isolate the incoming vibration. With the conventional automotive technologies, it is challenging to combine these two conflicting performance trade-offs, ride quality including handling, and NVH (noise, vibration and harshness). Over the last decades, MREs, one of the new emerging smart materials, have been widely used to resolve this technical limitation. For example, an advanced engine mount was developed by using MRE to isolate the vibration transmitting from engines. In this paper, we will focus on rear cross member bushes, which is a key component for isolating the vibration from the road, and demonstrate their improved performance by utilizing MRE. The resonance frequency shift induced by the stiffness change of MRE will be presented through the frequency response functions estimated by simulation result.

  3. Second-order schedules of token reinforcement with pigeons: effects of fixed- and variable-ratio exchange schedules.

    PubMed

    Foster, T A; Hackenberg, T D; Vaidya, M

    2001-09-01

    Pigeons' key pecks produced food under second-order schedules of token reinforcement, with light-emitting diodes serving as token reinforcers. In Experiment 1, tokens were earned according to a fixed-ratio 50 schedule and were exchanged for food according to either fixed-ratio or variable-ratio exchange schedules, with schedule type varied across conditions. In Experiment 2, schedule type was varied within sessions using a multiple schedule. In one component, tokens were earned according to a fixed-ratio 50 schedule and exchanged according to a variable-ratio schedule. In the other component, tokens were earned according to a variable-ratio 50 schedule and exchanged according to a fixed-ratio schedule. In both experiments, the number of responses per exchange was varied parametrically across conditions, ranging from 50 to 400 responses. Response rates decreased systematically with increases in the fixed-ratio exchange schedules, but were much less affected by changes in the variable-ratio exchange schedules. Response rates were consistently higher under variable-ratio exchange schedules than tinder comparable fixed-ratio exchange schedules, especially at higher exchange ratios. These response-rate differences were due both to greater pre-ratio pausing and to lower local rates tinder the fixed-ratio exchange schedules. Local response rates increased with proximity to food under the higher fixed-ratio exchange schedules, indicative of discriminative control by the tokens.

  4. Photoperiod- and temperature-mediated control of phenology in trees - a molecular perspective.

    PubMed

    Singh, Rajesh Kumar; Svystun, Tetiana; AlDahmash, Badr; Jönsson, Anna Maria; Bhalerao, Rishikesh P

    2017-01-01

    Contents 511 I. 511 II. 512 III. 513 IV. 513 V. 517 VI. 517 VII. 521 VIII. 521 Acknowledgements 521 References 521 SUMMARY: Trees growing in boreal and temperate regions synchronize their growth with seasonal climatic changes in adaptive responses that are essential for their survival. These trees cease growth before the winter and establish a dormant state during which growth cessation is maintained by repression of responses to growth-promotive signals. Reactivation of growth in the spring follows the release from dormancy promoted by prolonged exposure to low temperature during the winter. The timing of the key events and regulation of the molecular programs associated with the key stages of the annual growth cycle are controlled by two main environmental cues: photoperiod and temperature. Recently, key components mediating photoperiodic control of growth cessation and bud set have been identified, and striking similarities have been observed in signaling pathways controlling growth cessation in trees and floral transition in Arabidopsis. Although less well understood, the regulation of bud dormancy and bud burst may involve cell-cell communication and chromatin remodeling. Here, we discuss current knowledge of the molecular-level regulation of the annual growth cycle of woody trees in temperate and boreal regions, and identify key questions that need to be addressed in the future. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  5. Capturing how age-friendly communities foster positive health, social participation and health equity: a study protocol of key components and processes that promote population health in aging Canadians.

    PubMed

    Levasseur, Mélanie; Dubois, Marie-France; Généreux, Mélissa; Menec, Verena; Raina, Parminder; Roy, Mathieu; Gabaude, Catherine; Couturier, Yves; St-Pierre, Catherine

    2017-05-25

    To address the challenges of the global aging population, the World Health Organization promoted age-friendly communities as a way to foster the development of active aging community initiatives. Accordingly, key components (i.e., policies, services and structures related to the communities' physical and social environments) should be designed to be age-friendly and help all aging adults to live safely, enjoy good health and stay involved in their communities. Although age-friendly communities are believed to be a promising way to help aging Canadians lead healthy and active lives, little is known about which key components best foster positive health, social participation and health equity, and their underlying mechanisms. This study aims to better understand which and how key components of age-friendly communities best foster positive health, social participation and health equity in aging Canadians. Specifically, the research objectives are to: 1) Describe and compare age-friendly key components of communities across Canada 2) Identify key components best associated with positive health, social participation and health equity of aging adults 3) Explore how these key components foster positive health, social participation and health equity METHODS: A mixed-method sequential explanatory design will be used. The quantitative part will involve a survey of Canadian communities and secondary analysis of cross-sectional data from the Canadian Longitudinal Study on Aging (CLSA). The survey will include an age-friendly questionnaire targeting key components in seven domains: physical environment, housing options, social environment, opportunities for participation, community supports and healthcare services, transportation options, communication and information. The CLSA is a large, national prospective study representative of the Canadian aging population designed to examine health transitions and trajectories of adults as they age. In the qualitative part, a multiple case study will be conducted in five Canadian communities performing best on positive health, social participation and health equity. Building on new and existing collaborations and generating evidence from real-world interventions, the results of this project will help communities to promote age-friendly policies, services and structures which foster positive health, social participation and health equity at a population level.

  6. The MADS-box XAANTAL1 increases proliferation at the Arabidopsis root stem-cell niche and participates in transition to differentiation by regulating cell-cycle components

    PubMed Central

    García-Cruz, Karla V.; García-Ponce, Berenice; Garay-Arroyo, Adriana; Sanchez, María De La Paz; Ugartechea-Chirino, Yamel; Desvoyes, Bénédicte; Pacheco-Escobedo, Mario A.; Tapia-López, Rosalinda; Ransom-Rodríguez, Ivan; Gutierrez, Crisanto; Alvarez-Buylla, Elena R.

    2016-01-01

    Background Morphogenesis depends on the concerted modulation of cell proliferation and differentiation. Such modulation is dynamically adjusted in response to various external and internal signals via complex transcriptional regulatory networks that mediate between such signals and regulation of cell-cycle and cellular responses (proliferation, growth, differentiation). In plants, which are sessile, the proliferation/differentiation balance is plastically adjusted during their life cycle and transcriptional networks are important in this process. MADS-box genes are key developmental regulators in eukaryotes, but their role in cell proliferation and differentiation modulation in plants remains poorly studied. Methods We characterize the XAL1 loss-of-function xal1-2 allele and overexpression lines using quantitative cellular and cytometry analyses to explore its role in cell cycle, proliferation, stem-cell patterning and transition to differentiation. We used quantitative PCR and cellular markers to explore if XAL1 regulates cell-cycle components and PLETHORA1 (PLT1) gene expression, as well as confocal microscopy to analyse stem-cell niche organization. Key Results We previously showed that XAANTAL1 (XAL1/AGL12) is necessary for Arabidopsis root development as a promoter of cell proliferation in the root apical meristem. Here, we demonstrate that XAL1 positively regulates the expression of PLT1 and important components of the cell cycle: CYCD3;1, CYCA2;3, CYCB1;1, CDKB1;1 and CDT1a. In addition, we show that xal1-2 mutant plants have a premature transition to differentiation with root hairs appearing closer to the root tip, while endoreplication in these plants is partially compromised. Coincidently, the final size of cortex cells in the mutant is shorter than wild-type cells. Finally, XAL1 overexpression-lines corroborate that this transcription factor is able to promote cell proliferation at the stem-cell niche. Conclusion XAL1 seems to be an important component of the networks that modulate cell proliferation/differentiation transition and stem-cell proliferation during Arabidopsis root development; it also regulates several cell-cycle components. PMID:27474508

  7. Identification of the odour and chemical composition of alumina refinery air emissions.

    PubMed

    Coffey, P S; Ioppolo-Armanios, M

    2004-01-01

    Alcoa World Alumina Australia has undertaken comprehensive air emissions monitoring aimed at characterising and quantifying the complete range of emissions to the atmosphere from Bayer refining of alumina at its Western Australian refineries. To the best of our knowledge, this project represents the most complete air emissions inventory of a Bayer refinery conducted in the worldwide alumina industry. It adds considerably to knowledge of air emission factors available for use in emissions estimation required under national pollutant release and transfer registers (NPRTs), such as the Toxic Releases Inventory, USA, and the National Pollutant Inventory, Australia. It also allows the preliminary identification of the key chemical components responsible for characteristic alumina refinery odours and the contribution of these components to the quality, or hedonic tone, of the odours. The strength and acceptability of refinery odours to employees and neighbours appears to be dependent upon where and in what proportion the odorous gases have been emitted from the refineries. This paper presents the results of the programme and develops a basis for classifying the odour properties of the key emission sources in the alumina-refining process.

  8. Perceptual compression of magnitude-detected synthetic aperture radar imagery

    NASA Technical Reports Server (NTRS)

    Gorman, John D.; Werness, Susan A.

    1994-01-01

    A perceptually-based approach for compressing synthetic aperture radar (SAR) imagery is presented. Key components of the approach are a multiresolution wavelet transform, a bit allocation mask based on an empirical human visual system (HVS) model, and hybrid scalar/vector quantization. Specifically, wavelet shrinkage techniques are used to segregate wavelet transform coefficients into three components: local means, edges, and texture. Each of these three components is then quantized separately according to a perceptually-based bit allocation scheme. Wavelet coefficients associated with local means and edges are quantized using high-rate scalar quantization while texture information is quantized using low-rate vector quantization. The impact of the perceptually-based multiresolution compression algorithm on visual image quality, impulse response, and texture properties is assessed for fine-resolution magnitude-detected SAR imagery; excellent image quality is found at bit rates at or above 1 bpp along with graceful performance degradation at rates below 1 bpp.

  9. Midfrontal conflict-related theta-band power reflects neural oscillations that predict behavior.

    PubMed

    Cohen, Michael X; Donner, Tobias H

    2013-12-01

    Action monitoring and conflict resolution require the rapid and flexible coordination of activity in multiple brain regions. Oscillatory neural population activity may be a key physiological mechanism underlying such rapid and flexible network coordination. EEG power modulations of theta-band (4-8 Hz) activity over the human midfrontal cortex during response conflict have been proposed to reflect neural oscillations that support conflict detection and resolution processes. However, it has remained unclear whether this frequency-band-specific activity reflects neural oscillations or nonoscillatory responses (i.e., event-related potentials). Here, we show that removing the phase-locked component of the EEG did not reduce the strength of the conflict-related modulation of the residual (i.e., non-phase-locked) theta power over midfrontal cortex. Furthermore, within-subject regression analyses revealed that the non-phase-locked theta power was a significantly better predictor of the conflict condition than was the time-domain phase-locked EEG component. Finally, non-phase-locked theta power showed robust and condition-specific (high- vs. low-conflict) cross-trial correlations with reaction time, whereas the phase-locked component did not. Taken together, our results indicate that most of the conflict-related and behaviorally relevant midfrontal EEG signal reflects a modulation of ongoing theta-band oscillations that occurs during the decision process but is not phase-locked to the stimulus or to the response.

  10. Immediate early gene expression following exposure to acoustic and visual components of courtship in zebra finches.

    PubMed

    Avey, Marc T; Phillmore, Leslie S; MacDougall-Shackleton, Scott A

    2005-12-07

    Sensory driven immediate early gene expression (IEG) has been a key tool to explore auditory perceptual areas in the avian brain. Most work on IEG expression in songbirds such as zebra finches has focused on playback of acoustic stimuli and its effect on auditory processing areas such as caudal medial mesopallium (CMM) caudal medial nidopallium (NCM). However, in a natural setting, the courtship displays of songbirds (including zebra finches) include visual as well as acoustic components. To determine whether the visual stimulus of a courting male modifies song-induced expression of the IEG ZENK in the auditory forebrain we exposed male and female zebra finches to acoustic (song) and visual (dancing) components of courtship. Birds were played digital movies with either combined audio and video, audio only, video only, or neither audio nor video (control). We found significantly increased levels of Zenk response in the auditory region CMM in the two treatment groups exposed to acoustic stimuli compared to the control group. The video only group had an intermediate response, suggesting potential effect of visual input on activity in these auditory brain regions. Finally, we unexpectedly found a lateralization of Zenk response that was independent of sex, brain region, or treatment condition, such that Zenk immunoreactivity was consistently higher in the left hemisphere than in the right and the majority of individual birds were left-hemisphere dominant.

  11. Patient opinion regarding patient-centered medical home fundamentals.

    PubMed

    Wexler, Randell K; King, Dana E; Andrews, Mark

    2012-04-01

    Although conceptually there is agreement on how the Patient-Centered Medical Home (PCMH) should be organized, there is little information regarding which PCMH components are the most important to patients. An anonymous, voluntary survey was administered to patients at three US academic medical centers. Questions sought opinions regarding the National Committee for Quality Assurance's key components and essential elements of the PCMH. Analysis of the survey responses was conducted using SAS version 9.1. A total of 780 surveys were returned. Patients expressed believing strongly that the ability to coordinate care, help patients to manage their own disease, and track laboratory results were the most important aspects of a PCMH office. There were no differences in response to the survey according to age, sex, race, or site. Patients listed care coordination, patient self-management, and improved access to care as the top priority attributes of a PCMH. Patients were consistent in their opinions that care coordination, access, and patient self-management were the most important elements of a PCMH.

  12. Direct effects of recurrent hypoglycaemia on adrenal catecholamine release.

    PubMed

    Orban, Branly O; Routh, Vanessa H; Levin, Barry E; Berlin, Joshua R

    2015-01-01

    In Type 1 and advanced Type 2 diabetes mellitus, elevation of plasma epinephrine plays a key role in normalizing plasma glucose during hypoglycaemia. However, recurrent hypoglycaemia blunts this elevation of plasma epinephrine. To determine whether recurrent hypoglycaemia affects peripheral components of the sympatho-adrenal system responsible for epinephrine release, male rats were administered subcutaneous insulin daily for 3 days. These recurrent hypoglycaemic animals showed a smaller elevation of plasma epinephrine than saline-injected controls when subjected to insulin-induced hypoglycaemia. Electrical stimulation of an adrenal branch of the splanchnic nerve in recurrent hypoglycaemic animals elicited less release of epinephrine and norepinephrine than in controls, without a change in adrenal catecholamine content. Responsiveness of isolated, perfused adrenal glands to acetylcholine and other acetylcholine receptor agonists was also unchanged. These results indicate that recurrent hypoglycaemia compromised the efficacy with which peripheral neuronal activity stimulates adrenal catecholamine release and demonstrate that peripheral components of the sympatho-adrenal system were directly affected by recurrent hypoglycaemia. © The Author(s) 2014.

  13. Mechanism study of biopolymer hair as a coupled thermo-water responsive smart material

    NASA Astrophysics Data System (ADS)

    Xiao, Xueliang; Zhou, Hongtao; Qian, Kun

    2017-03-01

    Animal hairs existing broadly in nature are found to be effectively responsive to stimuli of heat and water in sequence for shape deformation and recovery, namely, coupled shape memory function (CSMF). In the paper, the ability of thermo-water sensitive CSMF was first time investigated for animal hairs, the structural and molecular networks for net-points and switches were therefrom identified. Experimentally, animal hair manifested a high ability of shape fixation in thermal processing and good shape recovery by water stimulus. Characterizations of two stimuli (heating and hydration) were performed systematically on hair’s deformation, recovery, viscoelasticity and chemical components (crystalline phase, key bonds inamorphous area). The variations of related chemical components in molecular networks were also explored. A hybrid structural network model was thereafter proposed to interpret the thermo-water sensitive CSMF of hair. This study of two-sequential-stimuli CSMF is original and inspired to explore more complex functions of other smart natural materials and expected to make much smarter synthetic polymers.

  14. Response efficacy: the key to minimizing rejection and maximizing acceptance of emotion-based anti-speeding messages.

    PubMed

    Lewis, I M; Watson, B; White, K M

    2010-03-01

    This study sought to improve understanding of the persuasive process of emotion-based appeals not only in relation to negative, fear-based appeals but also for appeals based upon positive emotions. In particular, the study investigated whether response efficacy, as a cognitive construct, mediated outcome measures of message effectiveness in terms of both acceptance and rejection of negative and positive emotion-based messages. Licensed drivers (N=406) participated via the completion of an on-line survey. Within the survey, participants received either a negative (fear-based) appeal or one of the two possible positive appeals (pride or humor-based). Overall, the study's findings confirmed the importance of emotional and cognitive components of persuasive health messages and identified response efficacy as a key cognitive construct influencing the effectiveness of not only fear-based messages but also positive emotion-based messages. Interestingly, however, the results suggested that response efficacy's influence on message effectiveness may differ for positive and negative emotion-based appeals such that significant indirect (and mediational) effects were found with both acceptance and rejection of the positive appeals yet only with rejection of the fear-based appeal. As such, the study's findings provide an important extension to extant literature and may inform future advertising message design. Copyright 2009 Elsevier Ltd. All rights reserved.

  15. Intelligence, Dataveillance, and Information Privacy

    NASA Astrophysics Data System (ADS)

    Mace, Robyn R.

    The extent and scope of intelligence activities are expanding in response to technological and economic transformations of the past decades. Intelligence efforts involving aggregated data from multiple public and private sources combined with past abuses of domestic intelligence functions have generated significant concerns among privacy advocates and citizens about the protection of individual civil liberties and information privacy from corporate and governmental misuse. In the information age, effective regulation and oversight are key components in the legitimacy and success of government domestic intelligence activities.

  16. Grating-assisted surface acoustic wave directional couplers

    NASA Astrophysics Data System (ADS)

    Golan, G.; Griffel, G.; Seidman, A.; Croitoru, N.

    1991-07-01

    Physical properties of novel grating-assisted Y directional couplers are examined using the coupled-mode theory. A general formalism for the analysis of the lateral perturbed directional coupler properties is presented. Explicit expressions for waveguide key parameters such as coupling length, grating period, and other structural characterizations, are obtained. The influence of other physical properties such as time and frequency response or cutoff conditions are also analyzed. A plane grating-assisted directional coupler is presented and examined as a basic component in the integrated acoustic technology.

  17. Insights into the role of neuronal glucokinase

    PubMed Central

    De Backer, Ivan; Hussain, Sufyan S.; Gardiner, James V.

    2016-01-01

    Glucokinase is a key component of the neuronal glucose-sensing mechanism and is expressed in brain regions that control a range of homeostatic processes. In this review, we detail recently identified roles for neuronal glucokinase in glucose homeostasis and counterregulatory responses to hypoglycemia and in regulating appetite. We describe clinical implications from these advances in our knowledge, especially for developing novel treatments for diabetes and obesity. Further research required to extend our knowledge and help our efforts to tackle the diabetes and obesity epidemics is suggested. PMID:27189932

  18. Microtubules as key cytoskeletal elements in cellular transport and shape changes: their expected responses to space environments

    NASA Technical Reports Server (NTRS)

    Conrad, G. W.; Conrad, A. H.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    Application of reference standard reagents to alternatively depolymerize or stabilize microtubules in a cell that undergoes very regular cytoskeleton-dependent shape changes provides a model system in which some expected components of the environments of spacecraft and space can be tested on Earth for their effects on the cytoskeleton. The fertilized eggs of Ilyanassa obsoleta undergo polar lobe formation by repeated, dramatic, constriction and relaxation of a microfilamentous band localized in the cortical cytoplasm and activated by microtubules.

  19. Identification of the In Vivo Phosphorylation Sites of the Ras Suppressor Rsu-1

    DTIC Science & Technology

    2000-12-11

    to phosphatidic acid (PA). Ras activation of the Raf serine/threonine kinases and activation of the MAPKs remains an important component of Ras...of either phospholipase C isofonns to yield DAG, or phospholipase D to yield phosphatidic acid and then DAG. Diacylglycerol is the key "on" switch...Rsu-I is phosphorylated in vivo in response to growth factor and TPA , a known activator of PKC. Phosphoamino acid analysis of Rsu- I suggests that

  20. Optimizing the Domestic Chemical, Biological, Radiological, and Nuclear Response Enterprise

    DTIC Science & Technology

    2015-03-01

    scope of this study was an issue with recall times, the time it takes to assemble the unit at its home location. A total of 13 of the 17 CERFPs surveyed...in the study were not 22 conducting exercises to determine how long a no-notice recall of their forces would ac- tually take, mainly because they...felt such experiences would create tensions between employers and NG members and would adversely affect the unit. Without rehearsing this key component

  1. Neuropathogenesis of Zika Virus in a Highly Susceptible Immunocompetent Mouse Model After Antibody Blockade of Type I Interferon

    DTIC Science & Technology

    2016-12-12

    of type I interferons on cells of the immune system. Clin Cancer Res 17: 755 2619-2627. 52. Le Bon A, Tough DF (2002) Links between innate and...debris, and inflammatory cell infiltrates. This model of ZIKV 45 pathogenesis will be valuable for evaluating medical countermeasures and the...The major limitation of these models is they utilize immunodeficient knockout mice that lack key components of the innate antiviral response. We

  2. Innovative Strategies for Breast Cancer Immunotherapy

    DTIC Science & Technology

    2014-09-01

    as well as T regulatory cells ( Tregs : FOXP3 and CD25 positive) were determined in K-CAR T cells obtained from BC patients or normal female donors...since Tregs are a component of the immune system that suppresses immune responses of other cells. A sample from a BC patient (#243, diagnosed with...33). Suppression of CD8+ effector cells by CD4+CD25+FoxP3+ regulatory T cells ( Tregs ) plays a key role in this immunosuppression (34). Our results

  3. Innovative Strategies for Breast Cancer Immunotherapy

    DTIC Science & Technology

    2014-09-01

    donors, percentages of CD4+ and CD8+ T cells as well as T regulatory cells ( Tregs : FOXP3 and CD25 positive) were determined in K-CAR T cells...obtained from BC patients or normal female donors, since Tregs are a component of the immune system that suppresses immune responses of other cells. A...immunosuppressive mechanisms that inhibit T cell activation (33). Suppression of CD8+ effector cells by CD4+CD25+FoxP3+ regulatory T cells ( Tregs ) plays a key role

  4. The supersonic molecular beam injector as a reliable tool for plasma fueling and physics experiment on HL-2A.

    PubMed

    Chen, C Y; Yu, D L; Feng, B B; Yao, L H; Song, X M; Zang, L G; Gao, X Y; Yang, Q W; Duan, X R

    2016-09-01

    On HL-2A tokamak, supersonic molecular beam injection (SMBI) has been developed as a routine refueling method. The key components of the system are an electromagnetic valve and a conic nozzle. The valve and conic nozzle are assembled to compose the simplified Laval nozzle for generating the pulsed beam. The appurtenance of the system includes the cooling system serving the cooled SMBI generation and the in situ calibration component for quantitative injection. Compared with the conventional gas puffing, the SMBI features prompt response and larger fueling flux. These merits devote the SMBI a good fueling method, an excellent plasma density feedback control tool, and an edge localized mode mitigation resource.

  5. Air pollution: mechanisms of neuroinflammation and CNS disease.

    PubMed

    Block, Michelle L; Calderón-Garcidueñas, Lilian

    2009-09-01

    Air pollution has been implicated as a chronic source of neuroinflammation and reactive oxygen species (ROS) that produce neuropathology and central nervous system (CNS) disease. Stroke incidence and Alzheimer's and Parkinson's disease pathology are linked to air pollution. Recent reports reveal that air pollution components reach the brain; systemic effects that impact lung and cardiovascular disease also impinge upon CNS health. While mechanisms driving air pollution-induced CNS pathology are poorly understood, new evidence suggests that microglial activation and changes in the blood-brain barrier are key components. Here we summarize recent findings detailing the mechanisms through which air pollution reaches the brain and activates the resident innate immune response to become a chronic source of pro-inflammatory factors and ROS, culminating in CNS disease.

  6. Satellite lidar and radar: Key components of the future climate observing system

    NASA Astrophysics Data System (ADS)

    Winker, D. M.

    2017-12-01

    Cloud feedbacks represent the dominant source of uncertainties in estimates of climate sensitivity and aerosols represent the largest source of uncertainty in climate forcing. Both observation of long-term changes and observational constraints on the processes responsible for those changes are necessary. The existing 30-year record of passive satellite observations has not yet provided constraints to significantly reduce these uncertainties, though. We now have more than a decade of experience with active sensors flying in the A-Train. These new observations have demonstrated the strengths of active sensors and the benefits of continued and more advanced active sensors. This talk will discuss the multiple roles for active sensors as an essential component of a global climate observing system.

  7. A Natural Component-Based Oxygen Indicator with In-Pack Activation for Intelligent Food Packaging.

    PubMed

    Won, Keehoon; Jang, Nan Young; Jeon, Junsu

    2016-12-28

    Intelligent food packaging can provide consumers with reliable and correct information on the quality and safety of packaged foods. One of the key constituents in intelligent packaging is a colorimetric oxygen indicator, which is widely used to detect oxygen gas involved in food spoilage by means of a color change. Traditional oxygen indicators consisting of redox dyes and strong reducing agents have two major problems: they must be manufactured and stored under anaerobic conditions because air depletes the reductant, and their components are synthetic and toxic. To address both of these serious problems, we have developed a natural component-based oxygen indicator characterized by in-pack activation. The conventional oxygen indicator composed of synthetic and artificial components was redesigned using naturally occurring compounds (laccase, guaiacol, and cysteine). These natural components were physically separated into two compartments by a fragile barrier. Only when the barrier was broken were all of the components mixed and the function as an oxygen indicator was begun (i.e., in-pack activation). Depending on the component concentrations, the natural component-based oxygen indicator exhibited different response times and color differences. The rate of the color change was proportional to the oxygen concentration. This novel colorimetric oxygen indicator will contribute greatly to intelligent packaging for healthier and safer foods.

  8. Characterization of an ntrX mutant of Neisseria gonorrhoeae reveals a response regulator that controls expression of respiratory enzymes in oxidase-positive proteobacteria.

    PubMed

    Atack, John M; Srikhanta, Yogitha N; Djoko, Karrera Y; Welch, Jessica P; Hasri, Norain H M; Steichen, Christopher T; Vanden Hoven, Rachel N; Grimmond, Sean M; Othman, Dk Seti Maimonah Pg; Kappler, Ulrike; Apicella, Michael A; Jennings, Michael P; Edwards, Jennifer L; McEwan, Alastair G

    2013-06-01

    NtrYX is a sensor-histidine kinase/response regulator two-component system that has had limited characterization in a small number of Alphaproteobacteria. Phylogenetic analysis of the response regulator NtrX showed that this two-component system is extensively distributed across the bacterial domain, and it is present in a variety of Betaproteobacteria, including the human pathogen Neisseria gonorrhoeae. Microarray analysis revealed that the expression of several components of the respiratory chain was reduced in an N. gonorrhoeae ntrX mutant compared to that in the isogenic wild-type (WT) strain 1291. These included the cytochrome c oxidase subunit (ccoP), nitrite reductase (aniA), and nitric oxide reductase (norB). Enzyme activity assays showed decreased cytochrome oxidase and nitrite reductase activities in the ntrX mutant, consistent with microarray data. N. gonorrhoeae ntrX mutants had reduced capacity to survive inside primary cervical cells compared to the wild type, and although they retained the ability to form a biofilm, they exhibited reduced survival within the biofilm compared to wild-type cells, as indicated by LIVE/DEAD staining. Analyses of an ntrX mutant in a representative alphaproteobacterium, Rhodobacter capsulatus, showed that cytochrome oxidase activity was also reduced compared to that in the wild-type strain SB1003. Taken together, these data provide evidence that the NtrYX two-component system may be a key regulator in the expression of respiratory enzymes and, in particular, cytochrome c oxidase, across a wide range of proteobacteria, including a variety of bacterial pathogens.

  9. Evaluating contribution of ionic, osmotic and oxidative stress components towards salinity tolerance in barley

    PubMed Central

    2014-01-01

    Background Salinity tolerance is a physiologically multi-faceted trait attributed to multiple mechanisms. Three barley (Hordeum vulgare) varieties contrasting in their salinity tolerance were used to assess the relative contribution of ionic, osmotic and oxidative stress components towards overall salinity stress tolerance in this species, both at the whole-plant and cellular levels. In addition, transcriptional changes in the gene expression profile were studied for key genes mediating plant ionic and oxidative homeostasis (NHX; RBOH; SOD; AHA and GORK), to compare a contribution of transcriptional and post-translational factors towards the specific components of salinity tolerance. Results Our major findings are two-fold. First, plant tissue tolerance was a dominating component that has determined the overall plant responses to salinity, with root K+ retention ability and reduced sensitivity to stress-induced hydroxyl radical production being the main contributing tolerance mechanisms. Second, it was not possible to infer which cultivars were salinity tolerant based solely on expression profiling of candidate genes at one specific time point. For the genes studied and the time point selected that transcriptional changes in the expression of these specific genes had a small role for barley’s adaptive responses to salinity. Conclusions For better tissue tolerance, sodium sequestration, K+ retention and resistance to oxidative stress all appeared to be crucial. Because these traits are highly interrelated, it is suggested that a major progress in crop breeding for salinity tolerance can be achieved only if these complementary traits are targeted at the same time. This study also highlights the essentiality of post translational modifications in plant adaptive responses to salinity. PMID:24774965

  10. Pathogens and Disease Play Havoc on the Host Epiproteome-The "First Line of Response" Role for Proteomic Changes Influenced by Disorder.

    PubMed

    Rikkerink, Erik H A

    2018-03-08

    Organisms face stress from multiple sources simultaneously and require mechanisms to respond to these scenarios if they are to survive in the long term. This overview focuses on a series of key points that illustrate how disorder and post-translational changes can combine to play a critical role in orchestrating the response of organisms to the stress of a changing environment. Increasingly, protein complexes are thought of as dynamic multi-component molecular machines able to adapt through compositional, conformational and/or post-translational modifications to control their largely metabolic outputs. These metabolites then feed into cellular physiological homeostasis or the production of secondary metabolites with novel anti-microbial properties. The control of adaptations to stress operates at multiple levels including the proteome and the dynamic nature of proteomic changes suggests a parallel with the equally dynamic epigenetic changes at the level of nucleic acids. Given their properties, I propose that some disordered protein platforms specifically enable organisms to sense and react rapidly as the first line of response to change. Using examples from the highly dynamic host-pathogen and host-stress response, I illustrate by example how disordered proteins are key to fulfilling the need for multiple levels of integration of response at different time scales to create robust control points.

  11. FUM2, a Cytosolic Fumarase, Is Essential for Acclimation to Low Temperature in Arabidopsis thaliana1[OPEN

    PubMed Central

    Dyson, Beth C.; Miller, Matthew A.E.; Feil, Regina; Rattray, Nicholas; Bowsher, Caroline G.

    2016-01-01

    Although cold acclimation is a key process in plants from temperate climates, the mechanisms sensing low temperature remain obscure. Here, we show that the accumulation of the organic acid fumaric acid, mediated by the cytosolic fumarase FUM2, is essential for cold acclimation of metabolism in the cold-tolerant model species Arabidopsis (Arabidopsis thaliana). A nontargeted metabolomic approach, using gas chromatography-mass spectrometry, identifies fumarate as a key component of the cold response in this species. Plants of T-DNA insertion mutants, lacking FUM2, show marked differences in their response to cold, with contrasting responses both in terms of metabolite concentrations and gene expression. The fum2 plants accumulated higher concentrations of phosphorylated sugar intermediates and of starch and malate. Transcripts for proteins involved in photosynthesis were markedly down-regulated in fum2.2 but not in wild-type Columbia-0. Plants of fum2 show a complete loss of the ability to acclimate photosynthesis to low temperature. We conclude that fumarate accumulation plays an essential role in low temperature sensing in Arabidopsis, either indirectly modulating metabolic or redox signals or possibly being itself directly involved in cold sensing. PMID:27440755

  12. Key Components in eHealth Interventions Combining Self-Tracking and Persuasive eCoaching to Promote a Healthier Lifestyle: A Scoping Review

    PubMed Central

    Oldenhuis, Hilbrand KE; de Groot, Martijn; Polstra, Louis; Velthuijsen, Hugo; van Gemert-Pijnen, Julia EWC

    2017-01-01

    Background The combination of self-tracking and persuasive eCoaching in automated interventions is a new and promising approach for healthy lifestyle management. Objective The aim of this study was to identify key components of self-tracking and persuasive eCoaching in automated healthy lifestyle interventions that contribute to their effectiveness on health outcomes, usability, and adherence. A secondary aim was to identify the way in which these key components should be designed to contribute to improved health outcomes, usability, and adherence. Methods The scoping review methodology proposed by Arskey and O’Malley was applied. Scopus, EMBASE, PsycINFO, and PubMed were searched for publications dated from January 1, 2013 to January 31, 2016 that included (1) self-tracking, (2) persuasive eCoaching, and (3) healthy lifestyle intervention. Results The search resulted in 32 publications, 17 of which provided results regarding the effect on health outcomes, 27 of which provided results regarding usability, and 13 of which provided results regarding adherence. Among the 32 publications, 27 described an intervention. The most commonly applied persuasive eCoaching components in the described interventions were personalization (n=24), suggestion (n=19), goal-setting (n=17), simulation (n=17), and reminders (n=15). As for self-tracking components, most interventions utilized an accelerometer to measure steps (n=11). Furthermore, the medium through which the user could access the intervention was usually a mobile phone (n=10). The following key components and their specific design seem to influence both health outcomes and usability in a positive way: reduction by setting short-term goals to eventually reach long-term goals, personalization of goals, praise messages, reminders to input self-tracking data into the technology, use of validity-tested devices, integration of self-tracking and persuasive eCoaching, and provision of face-to-face instructions during implementation. In addition, health outcomes or usability were not negatively affected when more effort was requested from participants to input data into the technology. The data extracted from the included publications provided limited ability to identify key components for adherence. However, one key component was identified for both usability and adherence, namely the provision of personalized content. Conclusions This scoping review provides a first overview of the key components in automated healthy lifestyle interventions combining self-tracking and persuasive eCoaching that can be utilized during the development of such interventions. Future studies should focus on the identification of key components for effects on adherence, as adherence is a prerequisite for an intervention to be effective. PMID:28765103

  13. A first application of independent component analysis to extracting structure from stock returns.

    PubMed

    Back, A D; Weigend, A S

    1997-08-01

    This paper explores the application of a signal processing technique known as independent component analysis (ICA) or blind source separation to multivariate financial time series such as a portfolio of stocks. The key idea of ICA is to linearly map the observed multivariate time series into a new space of statistically independent components (ICs). We apply ICA to three years of daily returns of the 28 largest Japanese stocks and compare the results with those obtained using principal component analysis. The results indicate that the estimated ICs fall into two categories, (i) infrequent large shocks (responsible for the major changes in the stock prices), and (ii) frequent smaller fluctuations (contributing little to the overall level of the stocks). We show that the overall stock price can be reconstructed surprisingly well by using a small number of thresholded weighted ICs. In contrast, when using shocks derived from principal components instead of independent components, the reconstructed price is less similar to the original one. ICA is shown to be a potentially powerful method of analyzing and understanding driving mechanisms in financial time series. The application to portfolio optimization is described in Chin and Weigend (1998).

  14. Exploring safety systems for dispensing in community pharmacies: focusing on how staff relate to organizational components.

    PubMed

    Harvey, Jasmine; Avery, Anthony J; Ashcroft, Darren; Boyd, Matthew; Phipps, Denham L; Barber, Nicholas

    2015-01-01

    Identifying risk is an important facet of a safety practice in an organization. To identify risk, all components within a system of operation should be considered. In clinical safety practice, a team of people, technologies, procedures and protocols, management structure and environment have been identified as key components in a system of operation. To explore risks in relation to prescription dispensing in community pharmacies by taking into account relationships between key components that relate to the dispensing process. Fifteen community pharmacies in England with varied characteristics were identified, and data were collected using non-participant observations, shadowing and interviews. Approximately 360 hours of observations and 38 interviews were conducted by the team. Observation field notes from each pharmacy were written into case studies. Overall, 52,500 words from 15 case studies and interview transcripts were analyzed using thematic and line-by-line analyses. Validation techniques included multiple data collectors co-authoring each case study for consensus, review of case studies by members of the wider team including academic and practicing community pharmacists, and patient safety experts and two presentations (internally and externally) to review and discuss findings. Risks identified were related to relationships between people and other key components in dispensing. This included how different levels of staff communicated internally and externally, followed procedures, interacted with technical systems, worked with management, and engaged with the environment. In a dispensing journey, the following categories were identified which show how risks are inextricably linked through relationships between human components and other key components: 1) dispensing with divided attention; 2) dispensing under pressure; 3) dispensing in a restricted space or environment; and, 4) managing external influences. To identify and evaluate risks effectively, an approach that includes understanding relationships between key components in dispensing is required. Since teams of people in community pharmacies are a key dispensing component, and therefore part of the operational process, it is important to note how they relate to other components in the environment within which they operate. Pharmacies can take the opportunity to reflect on the organization of their systems and review in particular how they can improve on the four key categories identified. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Multimodal switching of conformation and solubility in homocysteine derived polypeptides.

    PubMed

    Kramer, Jessica R; Deming, Timothy J

    2014-04-16

    We report the design and synthesis of poly(S-alkyl-L-homocysteine)s, which were found to be a new class of readily prepared, multiresponsive polymers that possess the unprecedented ability to respond in different ways to different stimuli, either through a change in chain conformation or in water solubility. The responsive properties of these materials are also effected under mild conditions and are completely reversible for all pathways. The key components of these polymers are the incorporation of water solubilizing alkyl functional groups that are integrated with precisely positioned, multiresponsive thioether linkages. This promising system allows multimodal switching of polypeptide properties to obtain desirable features, such as coupled responses to multiple external inputs.

  16. The impairment/disability distinction: a response to Shakespeare.

    PubMed

    Edwards, S D

    2008-01-01

    Tom Shakespeare's important new book includes, among other topics, a persuasive critique of the social model of disability. A key component in his case against that model consists in an argument against the impairment/disability distinction as this is understood within the social model. The present paper focuses on the case Shakespeare makes against that distinction. Three arguments mounted by Shakespeare are summarised and responded to. It is argued that the responses adequately rebut Shakespeare's case on this specific issue. Moreover, as the engagement with Shakespeare's argument illustrates, his claim to employ a critical realist perspective appears to be in considerable tension with the case he offers against the impairment/disability distinction.

  17. Evolving Systems: An Outcome of Fondest Hopes and Wildest Dreams

    NASA Technical Reports Server (NTRS)

    Frost, Susan A.; Balas, Mark J.

    2012-01-01

    New theory is presented for evolving systems, which are autonomously controlled subsystems that self-assemble into a new evolved system with a higher purpose. Evolving systems of aerospace structures often require additional control when assembling to maintain stability during the entire evolution process. This is the concept of Adaptive Key Component Control that operates through one specific component to maintain stability during the evolution. In addition, this control must often overcome persistent disturbances that occur while the evolution is in progress. Theoretical results will be presented for Adaptive Key Component control for persistent disturbance rejection. An illustrative example will demonstrate the Adaptive Key Component controller on a system composed of rigid body and flexible body modes.

  18. Transcriptome analyses reveal genotype- and developmental stage-specific molecular responses to drought and salinity stresses in chickpea

    PubMed Central

    Garg, Rohini; Shankar, Rama; Thakkar, Bijal; Kudapa, Himabindu; Krishnamurthy, Lakshmanan; Mantri, Nitin; Varshney, Rajeev K.; Bhatia, Sabhyata; Jain, Mukesh

    2016-01-01

    Drought and salinity are the major factors that limit chickpea production worldwide. We performed whole transcriptome analyses of chickpea genotypes to investigate the molecular basis of drought and salinity stress response/adaptation. Phenotypic analyses confirmed the contrasting responses of the chickpea genotypes to drought or salinity stress. RNA-seq of the roots of drought and salinity related genotypes was carried out under control and stress conditions at vegetative and/or reproductive stages. Comparative analysis of the transcriptomes revealed divergent gene expression in the chickpea genotypes at different developmental stages. We identified a total of 4954 and 5545 genes exclusively regulated in drought-tolerant and salinity-tolerant genotypes, respectively. A significant fraction (~47%) of the transcription factor encoding genes showed differential expression under stress. The key enzymes involved in metabolic pathways, such as carbohydrate metabolism, photosynthesis, lipid metabolism, generation of precursor metabolites/energy, protein modification, redox homeostasis and cell wall component biogenesis, were affected by drought and/or salinity stresses. Interestingly, transcript isoforms showed expression specificity across the chickpea genotypes and/or developmental stages as illustrated by the AP2-EREBP family members. Our findings provide insights into the transcriptome dynamics and components of regulatory network associated with drought and salinity stress responses in chickpea. PMID:26759178

  19. Subset of heat-shock transcription factors required for the early response of Arabidopsis to excess light

    PubMed Central

    Jung, Hou-Sung; Crisp, Peter A.; Estavillo, Gonzalo M.; Cole, Benjamin; Hong, Fangxin; Mockler, Todd C.; Pogson, Barry J.; Chory, Joanne

    2013-01-01

    Sunlight provides energy for photosynthesis and is essential for nearly all life on earth. However, too much or too little light or rapidly fluctuating light conditions cause stress to plants. Rapid changes in the amount of light are perceived as a change in the reduced/oxidized (redox) state of photosynthetic electron transport components in chloroplasts. However, how this generates a signal that is relayed to changes in nuclear gene expression is not well understood. We modified redox state in the reference plant, Arabidopsis thaliana, using either excess light or low light plus the herbicide DBMIB (2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone), a well-known inhibitor of photosynthetic electron transport. Modification of redox state caused a change in expression of a common set of about 750 genes, many of which are known stress-responsive genes. Among the most highly enriched promoter elements in the induced gene set were heat-shock elements (HSEs), known motifs that change gene expression in response to high temperature in many systems. We show that HSEs from the promoter of the ASCORBATE PEROXIDASE 2 (APX2) gene were necessary and sufficient for APX2 expression in conditions of excess light, or under low light plus the herbicide. We tested APX2 expression phenotypes in overexpression and loss-of-function mutants of 15 Arabidopsis A-type heat-shock transcription factors (HSFs), and identified HSFA1D, HSFA2, and HSFA3 as key factors regulating APX2 expression in diverse stress conditions. Excess light regulates both the subcellular location of HSFA1D and its biochemical properties, making it a key early component of the excess light stress network of plants. PMID:23918368

  20. Household Food Waste: Multivariate Regression and Principal Components Analyses of Awareness and Attitudes among U.S. Consumers

    PubMed Central

    2016-01-01

    We estimate models of consumer food waste awareness and attitudes using responses from a national survey of U.S. residents. Our models are interpreted through the lens of several theories that describe how pro-social behaviors relate to awareness, attitudes and opinions. Our analysis of patterns among respondents’ food waste attitudes yields a model with three principal components: one that represents perceived practical benefits households may lose if food waste were reduced, one that represents the guilt associated with food waste, and one that represents whether households feel they could be doing more to reduce food waste. We find our respondents express significant agreement that some perceived practical benefits are ascribed to throwing away uneaten food, e.g., nearly 70% of respondents agree that throwing away food after the package date has passed reduces the odds of foodborne illness, while nearly 60% agree that some food waste is necessary to ensure meals taste fresh. We identify that these attitudinal responses significantly load onto a single principal component that may represent a key attitudinal construct useful for policy guidance. Further, multivariate regression analysis reveals a significant positive association between the strength of this component and household income, suggesting that higher income households most strongly agree with statements that link throwing away uneaten food to perceived private benefits. PMID:27441687

  1. Variations in the perception of trauma-related complications between attending surgeons, surgery residents, critical care nurses, and medical students.

    PubMed

    Dissanaike, Sharmila; Berry, Matthew; Ginos, Jason; Paige, Robert; McNabb, Wendi; Griswold, John

    2009-06-01

    The morbidity and mortality conference (M&M) is a key component of the performance improvement process. The audience response system (ARS) has been shown to improve audience participation and promote more truthful responses in various settings. We implemented the ARS in our trauma M&M and evaluated the responses we received from different categories of participants. This was a prospective observational study undertaken between November 2006 and July 2007. Cases were graded based on the American College of Surgeons scoring system. We evaluated the responses of attending surgeons, residents, critical care nurses, and medical students using the ARS. We had 695 responses for complications and 936 responses for deaths. Residents consistently scored complications as more severe than other groups (P = .03). There was no difference in the scoring of deaths. Surgical residents assign higher severity to trauma-related complications than other groups when using an anonymous automated scoring system.

  2. A comprehensive grid to evaluate case management's expected effectiveness for community-dwelling frail older people: results from a multiple, embedded case study.

    PubMed

    Van Durme, Thérèse; Schmitz, Olivier; Cès, Sophie; Anthierens, Sibyl; Maggi, Patrick; Delye, Sam; De Almeida Mello, Johanna; Declercq, Anja; Macq, Jean; Remmen, Roy; Aujoulat, Isabelle

    2015-06-18

    Case management is a type of intervention expected to improve the quality of care and therefore the quality of life of frail, community-dwelling older people while delaying institutionalisation in nursing homes. However, the heterogeneity, multidimensionality and complexity of these interventions make their evaluation by the means of classical approaches inadequate. Our objective was twofold: (i) to propose a tool allowing for the identification of the key components that explain the success of case management for this population and (ii) to propose a typology based on the results of this tool. The process started with a multiple embedded case study design in order to identify the key components of case management. Based on the results of this first step, data were collected among 22 case management interventions, in order to evaluate their expected effectiveness. Finally, multiple correspondence analyses was conducted to propose a typology of case management. The overall approach was informed by Wagner's Chronic Care Model and the theory of complexity. The study identified a total of 23 interacting key components. Based on the clustering of response patterns of the 22 case management projects included in our study, three types of case management programmes were evidenced, situated on a continuum from a more "socially-oriented" type towards a more "clinically-oriented" type of case management. The type of feedback provided to the general practitioner about both the global geriatric assessment and the result of the intervention turned out to be the most discriminant component between the types. The study design allowed to produce a tool that can be used to distinguish between different types of case management interventions and further evaluate their effect on frail older people in terms of the delaying institutionalisation, functional and cognitive status, quality of life and societal costs.

  3. The Arabidopsis endoplasmic reticulum associated degradation pathways are involved in the regulation of heat stress response

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

    Li, Lin-Mao; University of Chinese Academy of Sciences, Beijing; Lü, Shi-You

    Abstracts: The Cytosolic Protein Response (CPR) in the cytosol and the Unfolded Protein Response (UPR) and ER-associated degradation (ERAD) in the endoplasmic reticulum are major pathways of the cellular proteostasis network. However, despite years of effort, how these protein quality control systems coordinated in vivo remains largely unknown, particularly in plants. In this study, the roles of two evolutionarily conserved ERAD pathways (DOA10 and HRD1) in heat stress response were investigated through reverse genetic approaches in Arabidopsis. Phenotypic analysis of the mutants showed that the two ERAD pathways additively play negative roles in heat tolerance, which was demonstrated by higher survivalmore » rate and lower electrolyte leakage in the loss of function mutants compared to the wild type plants. Importantly, gene expression analysis revealed that the mutant plants showed elevated transcriptional regulation of several downstream genes, including those encoding CPR and UPR marker genes, under both basal and heat stress conditions. Finally, multiple components of ERAD genes exhibited rapid response to increasing temperature. Taken together, our data not only unravels key insights into the crosstalk between different protein quality control processes, but also provides candidate genes to genetically improve plant heat tolerance in the future. - Highlights: • ERAD pathways cooperatively regulate plant thermotolerance. • ERAD pathways cooperatively regulate UPR and CPR. • ERAD components gene expression are upregulated by heat stress.« less

  4. Capsular Polysaccharide is a Main Component of Mycoplasma ovipneumoniae in the Pathogen-Induced Toll-Like Receptor-Mediated Inflammatory Responses in Sheep Airway Epithelial Cells

    PubMed Central

    Jiang, Zhongjia; Song, Fuyang; Li, Yanan; Xue, Di; Deng, Guangcun; Li, Min

    2017-01-01

    Mycoplasma ovipneumoniae (M. ovipneumoniae) is characterized as an etiological agent of primary atypical pneumonia that specifically infects sheep and goat. In an attempt to better understand the pathogen-host interaction between the invading M. ovipneumoniae and airway epithelial cells, we investigated the host inflammatory responses against capsular polysaccharide (designated as CPS) of M. ovipneumoniae using sheep bronchial epithelial cells cultured in an air-liquid interface (ALI) model. Results showed that CPS derived from M. ovipneumoniae could activate toll-like receptor- (TLR-) mediated inflammatory responses, along with an elevated expression of nuclear factor kappa B (NF-κB), activator protein-1 (AP-1), and interferon regulatory factor 3 (IRF3) as well as various inflammatory-associated mediators, representatively including proinflammatory cytokines, such as IL1β, TNFα, and IL8, and anti-inflammatory cytokines such as IL10 and TGFβ of TLR signaling cascade. Mechanistically, the CPS-induced inflammation was TLR initiated and was mediated by activations of both MyD88-dependent and MyD88-independent signaling pathways. Of importance, a blockage of CPS with specific antibody led a significant reduction of M. ovipneumoniae-induced inflammatory responses in sheep bronchial epithelial cells. These results suggested that CPS is a key virulent component of M. ovipneumoniae, which may play a crucial role in the inflammatory response induced by M. ovipneumoniae infections. PMID:28553017

  5. Atypical serum immunofixation patterns frequently emerge in immunomodulatory therapy and are associated with a high degree of response in multiple myeloma.

    PubMed

    Mark, Tomer; Jayabalan, David; Coleman, Morton; Pearse, Roger N; Wang, Y Lynn; Lent, Richard; Christos, Paul J; Lee, Joong W; Agrawal, Yash P; Matthew, Susan; Ely, Scott; Mazumdar, Madhu; Cesarman, Ethel; Leonard, John P; Furman, Richard R; Chen-Kiang, Selina; Niesvizky, Ruben

    2008-12-01

    The M-protein is the major reference measure for response in multiple myeloma (MM) and its correct interpretation is key to clinical management. The emergence of oligoclonal banding is recognized as a benign finding in the postautologous stem cell transplantation setting (ASCT) for MM but its significance during non-myeloablative therapy is unknown. In a study of the immunomodulatory combination BiRD, (lenalidomide and dexamethasone with clarithromycin), we frequently detected the emergence of mono- and oligo-clonal immunoglobulins unrelated to the baseline diagnostic M-protein. The new M-proteins seen on serum immunofixation electrophoresis were clearly different in either heavy or light chain component(s) from the original M-spike protein and were termed atypical serum immunofixation patterns (ASIPs). Overall, 24/72 (33%) patients treated with BiRD developed ASIPs. Patients who developed ASIPs compared with patients treated with BiRD without ASIPs, had a significantly greater overall response (100% vs. 85%) and complete response rates (71% vs. 23%). ASIPs were not associated with new clonal plasma cells or other lymphoproliferative processes, and molecular remissions were documented. This is the first time this phenomenon has been seen with regularity in non-myeloablative therapy for MM. Analogous to the ASCT experience, ASIPs do not signal incipient disease progression, but rather herald robust response.

  6. Spacesuit Portable Life Support System Breadboard (PLSS 1.0) Development and Test Results

    NASA Technical Reports Server (NTRS)

    Vogel, Matt R.; Watts, Carly

    2011-01-01

    A multi-year effort has been carried out at NASA-JSC to develop an advanced Extravehicular Activity (EVA) PLSS design intended to further the current state of the art by increasing operational flexibility, reducing consumables, and increasing robustness. Previous efforts have focused on modeling and analyzing the advanced PLSS architecture, as well as developing key enabling technologies. Like the current International Space Station (ISS) Extravehicular Mobility Unit (EMU) PLSS, the advanced PLSS comprises of three subsystems required to sustain the crew during EVA including the Thermal, Ventilation, and Oxygen Subsystems. This multi-year effort has culminated in the construction and operation of PLSS 1.0, a test rig that simulates full functionality of the advanced PLSS design. PLSS 1.0 integrates commercial off the shelf hardware with prototype technology development components, including the primary and secondary oxygen regulators, ventilation loop fan, Rapid Cycle Amine (RCA) swingbed, and Spacesuit Water Membrane Evaporator (SWME). Testing accumulated 239 hours over 45 days, while executing 172 test points. Specific PLSS 1.0 test objectives assessed during this testing include: confirming key individual components perform in a system level test as they have performed during component level testing; identifying unexpected system-level interactions; operating PLSS 1.0 in nominal steady-state EVA modes to baseline subsystem performance with respect to metabolic rate, ventilation loop pressure and flow rate, and environmental conditions; simulating nominal transient EVA operational scenarios; simulating contingency EVA operational scenarios; and further evaluating individual technology development components. Successful testing of the PLSS 1.0 provided a large database of test results that characterize system level and component performance. With the exception of several minor anomalies, the PLSS 1.0 test rig performed as expected; furthermore, many system responses trended in accordance with pre-test predictions.

  7. Manual Dexterity in Schizophrenia—A Neglected Clinical Marker?

    PubMed Central

    Térémetz, Maxime; Carment, Loïc; Brénugat-Herne, Lindsay; Croca, Marta; Bleton, Jean-Pierre; Krebs, Marie-Odile; Maier, Marc A.; Amado, Isabelle; Lindberg, Påvel G.

    2017-01-01

    Impaired manual dexterity is commonly observed in schizophrenia. However, a quantitative description of key sensorimotor components contributing to impaired dexterity is lacking. Whether the key components of dexterity are differentially affected and how they relate to clinical characteristics also remains unclear. We quantified the degree of dexterity in 35 stabilized patients with schizophrenia and in 20 age-matched control subjects using four visuomotor tasks: (i) force tracking to quantify visuomotor precision, (ii) sequential finger tapping to measure motor sequence recall, (iii) single-finger tapping to assess temporal regularity, and (iv) multi-finger tapping to measure independence of finger movements. Diverse clinical and neuropsychological tests were also applied. A patient subgroup (N = 15) participated in a 14-week cognitive remediation protocol and was assessed before and after remediation. Compared to control subjects, patients with schizophrenia showed greater error in force tracking, poorer recall of tapping sequences, decreased tapping regularity, and reduced degree of finger individuation. A composite performance measure discriminated patients from controls with sensitivity = 0.79 and specificity = 0.9. Aside from force-tracking error, no other dexterity components correlated with antipsychotic medication. In patients, some dexterity components correlated with neurological soft signs, Positive and Negative Syndrome Scale (PANSS), or neuropsychological scores. This suggests differential cognitive contributions to these components. Cognitive remediation lead to significant improvement in PANSS, tracking error, and sequence recall (without change in medication). These findings show that multiple aspects of sensorimotor control contribute to impaired manual dexterity in schizophrenia. Only visuomotor precision was related to antipsychotic medication. Good diagnostic accuracy and responsiveness to treatment suggest that manual dexterity may represent a useful clinical marker in schizophrenia. PMID:28740470

  8. Opportunities and constraints for developing a sustainable E-waste management system at local government level in Australia.

    PubMed

    Davis, Georgina; Herat, S

    2010-08-01

    E-waste refers to both electronic and electrical waste materials; namely any items which rely on an electric current or electromagnetic fields in order to operate, and contain a hard-drive or significant electronic components and/or a printed circuit board. E-waste is outstripping the general growth of the municipal waste stream. Increasingly, smaller and cheaper electronic items are being disposed of in municipal waste systems and this, coupled with an increase in the number of, and turnover of manufacturers and suppliers, may see local councils assuming a key role in future e-waste management. A survey of local councils across Australia was undertaken to determine the current level of understanding and action on e-waste, and to solicit key responses regarding the identification of areas where improvements could be made. The survey achieved an overall response rate of 35%. Survey results identified key barriers experienced by councils regarding the collection and treatment of e-wastes, such as access to reprocessing facilities and the limited or complete unawareness by the public of the issues. With regards to who should pay for e-waste disposal at end-of-life, consumers and producers were most commonly cited, depending on the state with the preferred funding mechanisms being 'advanced recycling fee' and Expanded Producer Responsibility. Overwhelmingly, 88% of respondents believed that federal legislation was required to manage e-waste. Overall, the results did not indicate differences in views between states for most questions.

  9. Analysing the bioactive makeup of demineralised dentine matrix on bone marrow mesenchymal stem cells for enhanced bone repair.

    PubMed

    Avery, S J; Sadaghiani, L; Sloan, A J; Waddington, R J

    2017-07-10

    Dentine matrix has proposed roles for directing mineralised tissue repair in dentine and bone; however, the range of bioactive components in dentine and specific biological effects on bone-derived mesenchymal stem cells (MSCs) in humans are less well understood. The aims of this study were to further elucidate the biological response of MSCs to demineralised dentine matrix (DDM) in enhancing wound repair responses and ascertain key contributing components. Dentine was obtained from human teeth and DDM proteins solubilised with ethylenediaminetetraacetic acid (EDTA). Bone marrow derived MSCs were commercially obtained. Cells with a more immature phenotype were then selected by preferential fibronectin adhesion (FN-BMMSCs) for use in subsequent in vitro assays. DDM at 10 µg/mL reduced cell expansion, attenuated apoptosis and was the minimal concentration capable of inducing osteoblastic differentiation. Enzyme-linked immunosorbent assay (ELISA) quantification of growth factors indicated physiological levels produced the above responses; transforming growth factor β (TGF-β1) was predominant (15.6 ng/mg DDM), with relatively lower concentrations of BMP-2, FGF, VEGF and PDGF (6.2-4.7 ng/mg DDM). Fractionation of growth factors from other DDM components by heparin affinity chromatography diminished osteogenic responses. Depletion of biglycan from DDM also attenuated osteogenic potency, which was partially rescued by the isolated biglycan. Decorin depletion from DDM had no influence on osteogenic potency. Collectively, these results demonstrate the potential of DDM for the delivery of physiological levels of growth factors for bone repair processes, and substantiate a role for biglycan as an additional adjuvant for driving osteogenic pathways.

  10. The twilight of immunity: emerging concepts in aging of the immune system.

    PubMed

    Nikolich-Žugich, Janko

    2018-01-01

    Immunosenescence is a series of age-related changes that affect the immune system and, with time, lead to increased vulnerability to infectious diseases. This Review addresses recent developments in the understanding of age-related changes that affect key components of immunity, including the effect of aging on cells of the (mostly adaptive) immune system, on soluble molecules that guide the maintenance and function of the immune system and on lymphoid organs that coordinate both the maintenance of lymphocytes and the initiation of immune responses. I further address the effect of the metagenome and exposome as key modifiers of immune-system aging and discuss a conceptual framework in which age-related changes in immunity might also affect the basic rules by which the immune system operates.

  11. Quantum optical circulator controlled by a single chirally coupled atom

    NASA Astrophysics Data System (ADS)

    Scheucher, Michael; Hilico, Adèle; Will, Elisa; Volz, Jürgen; Rauschenbeutel, Arno

    2016-12-01

    Integrated nonreciprocal optical components, which have an inherent asymmetry between their forward and backward propagation direction, are key for routing signals in photonic circuits. Here, we demonstrate a fiber-integrated quantum optical circulator operated by a single atom. Its nonreciprocal behavior arises from the chiral interaction between the atom and the transversally confined light. We demonstrate that the internal quantum state of the atom controls the operation direction of the circulator and that it features a strongly nonlinear response at the single-photon level. This enables, for example, photon number-dependent routing and novel quantum simulation protocols. Furthermore, such a circulator can in principle be prepared in a coherent superposition of its operational states and may become a key element for quantum information processing in scalable integrated optical circuits.

  12. Barriers and facilitators to establishing a national public health observatory.

    PubMed

    Pooransingh, Shalini; Misir, Akenath; Ramdath, Dan; Ramsewak, Samuel; Jaglal, Susan; Cameron, Cathy; Goel, Vivek

    2015-11-01

    To determine what stakeholders perceive as barriers and facilitators to creating a national public health observatory (PHO) in Trinidad and Tobago. A descriptive study was conducted based on 15 key informant interviews carried out from April to September 2013. The key informants worked within the health care sector in Trinidad and Tobago. Using a semi-structured interview guide, information was collected on knowledge, attitudes, and beliefs about creating a PHO; barriers and facilitators to creating and sustaining a PHO; legal considerations; and human resource and information technology requirements. Common themes of the responses were identified. The majority of participants supported the development of a national PHO, recognized its value in informing their work, and indicated that a national PHO could 1) provide information to support evidence-informed decision-making for health policy and strategic planning; 2) facilitate data management by establishing data policies, procedures, and standards; 3) increase the use of data by synthesizing and disseminating information; and 4) provide data for benchmarking. However, a number of barriers were identified, including 1) the perception that data collection is not valued; 2) untimely availability of data; 3) limited data synthesis, dissemination, and utilization to inform decision-making; and 4) challenges related to the allocation of human resources and existing information technology. Key informants support the development of a national PHO in Trinidad and Tobago. The findings align well within the components of the conceptual framework for establishing national health observatories. A stepwise approach to establishing a national PHO in Trinidad and Tobago, beginning with structural components and followed by functional components, is recommended. A national PHO in Trinidad and Tobago could serve as a model for other countries in the Caribbean.

  13. Herbivore impacts to the moss layer determine tundra ecosystem response to grazing and warming.

    PubMed

    Gornall, Jemma L; Woodin, Sarah J; Jónsdóttir, Ingibjörg S; Van der Wal, Rene

    2009-10-01

    Herbivory and climate are key environmental drivers, shaping ecosystems at high latitudes. Here, we focus on how these two drivers act in concert, influencing the high arctic tundra. We aim to investigate mechanisms through which herbivory by geese influences vegetation and soil processes in tundra ecosystems under ambient and warmed conditions. To achieve this, two grazing treatments, clipping plus faecal additions and moss removal, were implemented in conjunction with passive warming. Our key finding was that, in many cases, the tundra ecosystem response was determined by treatment impacts on the moss layer. Moss removal reduced the remaining moss layer depth by 30% and increased peak grass biomass by 27%. These impacts were probably due to observed higher soil temperatures and decomposition rates associated with moss removal. The positive impact of moss removal on grass biomass was even greater with warming, further supporting this conclusion. In contrast, moss removal reduced dwarf shrub biomass possibly resulting from increased exposure to desiccating winds. An intact moss layer buffered the soil to increased air temperature and as a result there was no response of vascular plant productivity to warming over the course of this study. In fact, moss removal impacts on soil temperature were nearly double those of warming, suggesting that the moss layer is a key component in controlling soil conditions. The moss layer also absorbed nutrients from faeces, promoting moss growth. We conclude that both herbivory and warming influence this high arctic ecosystem but that herbivory is the stronger driver of the two. Disturbance to the moss layer resulted in a shift towards a more grass-dominated system with less abundant mosses and shrubs, a trend that was further enhanced by warming. Thus herbivore impacts to the moss layer are key to understanding arctic ecosystem response to grazing and warming.

  14. A Cognitive Task Analysis of Information Management Strategies in a Computerized Provider Order Entry Environment

    PubMed Central

    Weir, Charlene R.; Nebeker, Jonathan J.R.; Hicken, Bret L.; Campo, Rebecca; Drews, Frank; LeBar, Beth

    2007-01-01

    Objective Computerized Provider Order Entry (CPOE) with electronic documentation, and computerized decision support dramatically changes the information environment of the practicing clinician. Prior work patterns based on paper, verbal exchange, and manual methods are replaced with automated, computerized, and potentially less flexible systems. The objective of this study is to explore the information management strategies that clinicians use in the process of adapting to a CPOE system using cognitive task analysis techniques. Design Observation and semi-structured interviews were conducted with 88 primary-care clinicians at 10 Veterans Administration Medical Centers. Measurements Interviews were taped, transcribed, and extensively analyzed to identify key information management goals, strategies, and tasks. Tasks were aggregated into groups, common components across tasks were clarified, and underlying goals and strategies identified. Results Nearly half of the identified tasks were not fully supported by the available technology. Six core components of tasks were identified. Four meta-cognitive information management goals emerged: 1) Relevance Screening; 2) Ensuring Accuracy; 3) Minimizing memory load; and 4) Negotiating Responsibility. Strategies used to support these goals are presented. Conclusion Users develop a wide array of information management strategies that allow them to successfully adapt to new technology. Supporting the ability of users to develop adaptive strategies to support meta-cognitive goals is a key component of a successful system. PMID:17068345

  15. Gene expression profiling of human alveolar macrophages infected by B. anthracis spores demonstrates TNF-α and NF-κb are key components of the innate immune response to the pathogen

    PubMed Central

    2009-01-01

    Background Bacillus anthracis, the etiologic agent of anthrax, has recently been used as an agent of bioterrorism. The innate immune system initially appears to contain the pathogen at the site of entry. Because the human alveolar macrophage (HAM) plays a key role in lung innate immune responses, studying the HAM response to B. anthracis is important in understanding the pathogenesis of the pulmonary form of this disease. Methods In this paper, the transcriptional profile of B. anthracis spore-treated HAM was compared with that of mock-infected cells, and differentially expressed genes were identified by Affymetrix microarray analysis. A portion of the results were verified by Luminex protein analysis. Results The majority of genes modulated by spores were upregulated, and a lesser number were downregulated. The differentially expressed genes were subjected to Ingenuity Pathway analysis, the Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis, the Promoter Analysis and Interaction Network Toolset (PAINT) and Oncomine analysis. Among the upregulated genes, we identified a group of chemokine ligand, apoptosis, and, interestingly, keratin filament genes. Central hubs regulating the activated genes were TNF-α, NF-κB and their ligands/receptors. In addition to TNF-α, a broad range of cytokines was induced, and this was confirmed at the level of translation by Luminex multiplex protein analysis. PAINT analysis revealed that many of the genes affected by spores contain the binding site for c-Rel, a member of the NF-κB family of transcription factors. Other transcription regulatory elements contained in many of the upregulated genes were c-Myb, CP2, Barbie Box, E2F and CRE-BP1. However, many of the genes are poorly annotated, indicating that they represent novel functions. Four of the genes most highly regulated by spores have only previously been associated with head and neck and lung carcinomas. Conclusion The results demonstrate not only that TNF-α and NF-κb are key components of the innate immune response to the pathogen, but also that a large part of the mechanisms by which the alveolar macrophage responds to B. anthracis are still unknown as many of the genes involved are poorly annotated. PMID:19744333

  16. A network analysis of the Chinese medicine Lianhua-Qingwen formula to identify its main effective components.

    PubMed

    Wang, Chun-Hua; Zhong, Yi; Zhang, Yan; Liu, Jin-Ping; Wang, Yue-Fei; Jia, Wei-Na; Wang, Guo-Cai; Li, Zheng; Zhu, Yan; Gao, Xiu-Mei

    2016-02-01

    Chinese medicine is known to treat complex diseases with multiple components and multiple targets. However, the main effective components and their related key targets and functions remain to be identified. Herein, a network analysis method was developed to identify the main effective components and key targets of a Chinese medicine, Lianhua-Qingwen Formula (LQF). The LQF is commonly used for the prevention and treatment of viral influenza in China. It is composed of 11 herbs, gypsum and menthol with 61 compounds being identified in our previous work. In this paper, these 61 candidate compounds were used to find their related targets and construct the predicted-target (PT) network. An influenza-related protein-protein interaction (PPI) network was constructed and integrated with the PT network. Then the compound-effective target (CET) network and compound-ineffective target network (CIT) were extracted, respectively. A novel approach was developed to identify effective components by comparing CET and CIT networks. As a result, 15 main effective components were identified along with 61 corresponding targets. 7 of these main effective components were further experimentally validated to have antivirus efficacy in vitro. The main effective component-target (MECT) network was further constructed with main effective components and their key targets. Gene Ontology (GO) analysis of the MECT network predicted key functions such as NO production being modulated by the LQF. Interestingly, five effective components were experimentally tested and exhibited inhibitory effects on NO production in the LPS induced RAW 264.7 cell. In summary, we have developed a novel approach to identify the main effective components in a Chinese medicine LQF and experimentally validated some of the predictions.

  17. Economic and Physical Linkages of the Information and Communication Technology (ICT) Service Industry to Key Industries of the Economy: An Ad Hoc Report

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

    Anderson, David M.; Hoffman, Michael G.; Niemeyer, Jackie M.

    This report examines the information and communications technology (ICT) services industry in response to an inquiry by the Department of Energy’s (DOE’s) Office of Energy Policy and Systems Analysis. The report answers several key questions: •How has the reliance on ICT services evolved in recent years for key infrastructure services such as air travel, freight transport, electricity and natural gas distribution, financial services, and critical health care, and for the household sector? •What ICT industry trends explain continued strong linkage to and reliance upon ICT? •What is the ICT industry’s reliance on grid-supplied power, uninterruptible power supplies, emergency generators andmore » back-up energy storage technologies? •What are the observed direct effects of ICT disruptions induced by electrical system failures in recent history and how resilient are the components of the ICT industry?« less

  18. Sphingolipids role in the regulation of inflammatory response: From leukocyte biology to bacterial infection.

    PubMed

    Chiricozzi, Elena; Loberto, Nicoletta; Schiumarini, Domitilla; Samarani, Maura; Mancini, Giulia; Tamanini, Anna; Lippi, Giuseppe; Dechecchi, Maria Cristina; Bassi, Rosaria; Giussani, Paola; Aureli, Massimo

    2018-03-01

    Sphingolipids (SLs) are amphiphilic molecules mainly associated with the external leaflet of eukaryotic plasma membrane, and are structural membrane components with key signaling properties. Since the beginning of the last century, a large number of papers described the involvement of these molecules in several aspects of cell physiology and pathology. Several lines of evidence support the critical role of SLs in inflammatory diseases, by acting as anti- or pro-inflammatory mediators. They are involved in control of leukocyte activation and migration, and are recognized as essential players in host response to pathogenic infection. We propose here a critical overview of current knowledge on involvement of different classes of SLs in inflammation, focusing on the role of simple and complex SLs in pathogen-mediated inflammatory response. ©2018 Society for Leukocyte Biology.

  19. Key Components in eHealth Interventions Combining Self-Tracking and Persuasive eCoaching to Promote a Healthier Lifestyle: A Scoping Review.

    PubMed

    Lentferink, Aniek J; Oldenhuis, Hilbrand Ke; de Groot, Martijn; Polstra, Louis; Velthuijsen, Hugo; van Gemert-Pijnen, Julia Ewc

    2017-08-01

    The combination of self-tracking and persuasive eCoaching in automated interventions is a new and promising approach for healthy lifestyle management. The aim of this study was to identify key components of self-tracking and persuasive eCoaching in automated healthy lifestyle interventions that contribute to their effectiveness on health outcomes, usability, and adherence. A secondary aim was to identify the way in which these key components should be designed to contribute to improved health outcomes, usability, and adherence. The scoping review methodology proposed by Arskey and O'Malley was applied. Scopus, EMBASE, PsycINFO, and PubMed were searched for publications dated from January 1, 2013 to January 31, 2016 that included (1) self-tracking, (2) persuasive eCoaching, and (3) healthy lifestyle intervention. The search resulted in 32 publications, 17 of which provided results regarding the effect on health outcomes, 27 of which provided results regarding usability, and 13 of which provided results regarding adherence. Among the 32 publications, 27 described an intervention. The most commonly applied persuasive eCoaching components in the described interventions were personalization (n=24), suggestion (n=19), goal-setting (n=17), simulation (n=17), and reminders (n=15). As for self-tracking components, most interventions utilized an accelerometer to measure steps (n=11). Furthermore, the medium through which the user could access the intervention was usually a mobile phone (n=10). The following key components and their specific design seem to influence both health outcomes and usability in a positive way: reduction by setting short-term goals to eventually reach long-term goals, personalization of goals, praise messages, reminders to input self-tracking data into the technology, use of validity-tested devices, integration of self-tracking and persuasive eCoaching, and provision of face-to-face instructions during implementation. In addition, health outcomes or usability were not negatively affected when more effort was requested from participants to input data into the technology. The data extracted from the included publications provided limited ability to identify key components for adherence. However, one key component was identified for both usability and adherence, namely the provision of personalized content. This scoping review provides a first overview of the key components in automated healthy lifestyle interventions combining self-tracking and persuasive eCoaching that can be utilized during the development of such interventions. Future studies should focus on the identification of key components for effects on adherence, as adherence is a prerequisite for an intervention to be effective. ©Aniek J Lentferink, Hilbrand KE Oldenhuis, Martijn de Groot, Louis Polstra, Hugo Velthuijsen, Julia EWC van Gemert-Pijnen. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 01.08.2017.

  20. A four-component synthetic attractant for Drosophila suzukii (Diptera: Drosophilidae) isolated from fermented bait headspace.

    PubMed

    Cha, Dong H; Adams, Todd; Werle, Christopher T; Sampson, Blair J; Adamczyk, John J; Rogg, Helmuth; Landolt, Peter J

    2014-02-01

    A mixture of wine and vinegar is more attractive than wine or vinegar to spotted wing drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), and ethanol and acetic acid are considered key to that attractiveness. In addition to ethanol and acetic acid, 13 other wine and vinegar volatiles are antennally active to D. suzukii and might be involved in food finding. Out of the 13 antennally active chemicals, acetoin, ethyl lactate and methionol increased fly response to a mixture of acetic acid and ethanol in field trapping experiments. A five-component blend of acetic acid, ethanol, acetoin, ethyl lactate and methionol was as attractive as the starting mixture of wine and vinegar in field tests conducted in the states of Oregon and Mississippi. Subtracting ethyl lactate from the five-component blend did not reduce the captures of flies in the trap. However, subtracting any other compound from the blend significantly reduced the numbers of flies captured. These results indicate that acetic acid, ethanol, acetoin and methionol are key olfactory cues for D. suzukii when attracted to wine and vinegar, which may be food-finding behavior leading flies to fermenting fruit in nature. It is anticipated that this four-component blend can be used as a highly attractive chemical lure for detection and management of D. suzukii. Published 2013. This article is a U.S. Government work and is in the public domain in the USA. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  1. Monitoring and accountability for the Pacific response to the non-communicable diseases crisis.

    PubMed

    Tolley, Hilary; Snowdon, Wendy; Wate, Jillian; Durand, A Mark; Vivili, Paula; McCool, Judith; Novotny, Rachel; Dewes, Ofa; Hoy, Damian; Bell, Colin; Richards, Nicola; Swinburn, Boyd

    2016-09-10

    Non-communicable diseases (NCD) are the leading cause of premature death and disability in the Pacific. In 2011, Pacific Forum Leaders declared "a human, social and economic crisis" due to the significant and growing burden of NCDs in the region. In 2013, Pacific Health Ministers' commitment to 'whole of government' strategy prompted calls for the development of a robust, sustainable, collaborative NCD monitoring and accountability system to track, review and propose remedial action to ensure progress towards the NCD goals and targets. The purpose of this paper is to describe a regional, collaborative framework for coordination, innovation and application of NCD monitoring activities at scale, and to show how they can strengthen accountability for action on NCDs in the Pacific. A key component is the Dashboard for NCD Action which aims to strengthen mutual accountability by demonstrating national and regional progress towards agreed NCD policies and actions. The framework for the Pacific Monitoring Alliance for NCD Action (MANA) draws together core country-level components of NCD monitoring data (mortality, morbidity, risk factors, health system responses, environments, and policies) and identifies key cross-cutting issues for strengthening national and regional monitoring systems. These include: capacity building; a regional knowledge exchange hub; innovations (monitoring childhood obesity and food environments); and a robust regional accountability system. The MANA framework is governed by the Heads of Health and operationalised by a multi-agency technical Coordination Team. Alliance membership is voluntary and non-conditional, and aims to support the 22 Pacific Island countries and territories to improve the quality of NCD monitoring data across the region. In establishing a common vision for NCD monitoring, the framework combines data collected under the WHO Global Framework for NCDs with a set of action-orientated indicators captured in a NCD Dashboard for Action. Viewing NCD monitoring as a multi-component system and providing a robust, transparent mutual accountability mechanism helps align agendas, roles and responsibilities of countries and support organisations. The dashboard provides a succinct communication tool for reporting progress on implementation of agreed policies and actions and its flexible methodology can be easily expanded, or adapted for other regions.

  2. BLISTER Regulates Polycomb-Target Genes, Represses Stress-Regulated Genes and Promotes Stress Responses in Arabidopsis thaliana.

    PubMed

    Kleinmanns, Julia A; Schatlowski, Nicole; Heckmann, David; Schubert, Daniel

    2017-01-01

    HIGHLIGHTS The PRC2 interacting protein BLISTER likely acts downstream of PRC2 to silence Polycomb target genes and is a key regulator of specific stress responses in Arabidopsis . Polycomb group (PcG) proteins are key epigenetic regulators of development. The highly conserved Polycomb repressive complex 2 (PRC2) represses thousands of target genes by trimethylating H3K27 (H3K27me3). Plant specific PcG components and functions are largely unknown, however, we previously identified the plant-specific protein BLISTER (BLI) as a PRC2 interactor. BLI regulates PcG target genes and promotes cold stress resistance. To further understand the function of BLI , we analyzed the transcriptional profile of bli-1 mutants. Approximately 40% of the up-regulated genes in bli are PcG target genes, however, bli-1 mutants did not show changes in H3K27me3 levels at all tested genes, indicating that BLI regulates PcG target genes downstream of or in parallel to PRC2. Interestingly, a significant number of BLI regulated H3K27me3 target genes is regulated by the stress hormone absciscic acid (ABA). We further reveal an overrepresentation of genes responding to abiotic stresses such as drought, high salinity, or heat stress among the up-regulated genes in bli mutants. Consistently, bli mutants showed reduced desiccation stress tolerance. We conclude that the PRC2 associated protein BLI is a key regulator of stress-responsive genes in Arabidopsis : it represses ABA-responsive PcG target genes, likely downstream of PRC2, and promotes resistance to several stresses such as cold and drought.

  3. A user interface framework for the Square Kilometre Array: concepts and responsibilities

    NASA Astrophysics Data System (ADS)

    Marassi, Alessandro; Brajnik, Giorgio; Nicol, Mark; Alberti, Valentina; Le Roux, Gerhard

    2016-07-01

    The Square Kilometre Array (SKA) project is responsible for developing the SKA Observatory, the world's largest radio telescope, with eventually over a square kilometre of collecting area and including a general headquarters as well as two radio telescopes: SKA1-Mid in South Africa and SKA1-Low in Australia. The SKA project consists of a number of subsystems (elements) among which the Telescope Manager (TM) is the one involved in controlling and monitoring the SKA telescopes. The TM element has three primary responsibilities: management of astronomical observations, management of telescope hardware and software subsystems, management of data to support system operations and all stakeholders (operators, maintainers, engineers and science users) in achieving operational, maintenance and engineering goals. Operators, maintainers, engineers and science users will interact with TM via appropriate user interfaces (UI). The TM UI framework envisaged is a complete set of general technical solutions (components, technologies and design information) for implementing a generic computing system (UI platform). Such a system will enable UI components to be instantiated to allow for human interaction via screens, keyboards, mouse and to implement the necessary logic for acquiring or deriving the information needed for interaction. It will provide libraries and specific Application Programming Interfaces (APIs) to implement operator and engineer interactive interfaces. This paper will provide a status update of the TM UI framework, UI platform and UI components design effort, including the technology choices, and discuss key challenges in the TM UI architecture, as well as our approaches to addressing them.

  4. The Top Five “Game Changers” in Vaccinology: Toward Rational and Directed Vaccine Development

    PubMed Central

    Kennedy, Richard B.

    2011-01-01

    Abstract Despite the tremendous success of the classical “isolate, inactivate, and inject” approach to vaccine development, new breakthroughs in vaccine research are increasingly reliant on novel approaches that incorporate cutting edge technology and advances in innate and adaptive immunology, microbiology, virology, pathogen biology, genetics, bioinformatics, and many other disciplines in order to: (1) deepen our understanding of the key biological processes that lead to protective immunity, (2) observe vaccine responses on a global, systems level, and (3) directly apply the new knowledge gained to the development of next-generation vaccines with improved safety profiles, enhanced efficacy, and even targeted utility in select populations. Here we highlight five key components foundational to vaccinomics efforts: applied immunogenomics, next generation sequencing and other cutting-edge “omics” technologies, advanced bioinformatics and analysis techniques, and finally, systems biology applied to immune profiling and vaccine responses. We believe these “game changers” will play a critical role in moving us toward the rational and directed development of new vaccines in the 21st century. PMID:21815811

  5. Influence of removal of invisible fixation on the saccadic and manual gap effect.

    PubMed

    Ueda, Hiroshi; Takahashi, Kohske; Watanabe, Katsumi

    2014-01-01

    Saccadic and manual reactions to a peripherally presented target are facilitated by removing a central fixation stimulus shortly before a target onset (the gap effect). The present study examined the effects of removal of a visible and invisible fixation point on the saccadic gap effect and the manual gap effect. Participants were required to fixate a central fixation point and respond to a peripherally presented target as quickly and accurately as possible by making a saccade (Experiment 1) or pressing a corresponding key (Experiment 2). The fixation point was dichoptically presented, and visibility was manipulated by using binocular rivalry and continuous flash suppression technique. In both saccade and key-press tasks, removing the visible fixation strongly quickened the responses. Furthermore, the invisible fixation, which remained on the display but suppressed, significantly delayed the saccadic response. Contrarily, the invisible fixation had no effect on the manual task. These results indicate that partially different processes mediate the saccadic gap effect and the manual gap effect. In particular, unconscious processes might modulate an oculomotor-specific component of the saccadic gap effect, presumably via subcortical mechanisms.

  6. Probabilistic inversion of expert assessments to inform projections about Antarctic ice sheet responses.

    PubMed

    Fuller, Robert William; Wong, Tony E; Keller, Klaus

    2017-01-01

    The response of the Antarctic ice sheet (AIS) to changing global temperatures is a key component of sea-level projections. Current projections of the AIS contribution to sea-level changes are deeply uncertain. This deep uncertainty stems, in part, from (i) the inability of current models to fully resolve key processes and scales, (ii) the relatively sparse available data, and (iii) divergent expert assessments. One promising approach to characterizing the deep uncertainty stemming from divergent expert assessments is to combine expert assessments, observations, and simple models by coupling probabilistic inversion and Bayesian inversion. Here, we present a proof-of-concept study that uses probabilistic inversion to fuse a simple AIS model and diverse expert assessments. We demonstrate the ability of probabilistic inversion to infer joint prior probability distributions of model parameters that are consistent with expert assessments. We then confront these inferred expert priors with instrumental and paleoclimatic observational data in a Bayesian inversion. These additional constraints yield tighter hindcasts and projections. We use this approach to quantify how the deep uncertainty surrounding expert assessments affects the joint probability distributions of model parameters and future projections.

  7. Functional characterization of p53 pathway components in the ancient metazoan Trichoplax adhaerens

    NASA Astrophysics Data System (ADS)

    Siau, Jia Wei; Coffill, Cynthia R.; Zhang, Weiyun Villien; Tan, Yaw Sing; Hundt, Juliane; Lane, David; Verma, Chandra; Ghadessy, Farid

    2016-09-01

    The identification of genes encoding a p53 family member and an Mdm2 ortholog in the ancient placozoan Trichoplax adhaerens advocates for the evolutionary conservation of a pivotal stress-response pathway observed in all higher eukaryotes. Here, we recapitulate several key functionalities ascribed to this known interacting protein pair by analysis of the placozoan proteins (Tap53 and TaMdm2) using both in vitro and cellular assays. In addition to interacting with each other, the Tap53 and TaMdm2 proteins are also able to respectively bind human Mdm2 and p53, providing strong evidence for functional conservation. The key p53-degrading function of Mdm2 is also conserved in TaMdm2. Tap53 retained DNA binding associated with p53 transcription activation function. However, it lacked transactivation function in reporter genes assays using a heterologous cell line, suggesting a cofactor incompatibility. Overall, the data supports functional roles for TaMdm2 and Tap53, and further defines the p53 pathway as an evolutionary conserved fulcrum mediating cellular response to stress.

  8. Crop improvement using life cycle datasets acquired under field conditions.

    PubMed

    Mochida, Keiichi; Saisho, Daisuke; Hirayama, Takashi

    2015-01-01

    Crops are exposed to various environmental stresses in the field throughout their life cycle. Modern plant science has provided remarkable insights into the molecular networks of plant stress responses in laboratory conditions, but the responses of different crops to environmental stresses in the field need to be elucidated. Recent advances in omics analytical techniques and information technology have enabled us to integrate data from a spectrum of physiological metrics of field crops. The interdisciplinary efforts of plant science and data science enable us to explore factors that affect crop productivity and identify stress tolerance-related genes and alleles. Here, we describe recent advances in technologies that are key components for data driven crop design, such as population genomics, chronological omics analyses, and computer-aided molecular network prediction. Integration of the outcomes from these technologies will accelerate our understanding of crop phenology under practical field situations and identify key characteristics to represent crop stress status. These elements would help us to genetically engineer "designed crops" to prevent yield shortfalls because of environmental fluctuations due to future climate change.

  9. A discussion on the merits and limitations of using drive-by monitoring to detect localised damage in a bridge

    NASA Astrophysics Data System (ADS)

    Hester, David; González, Arturo

    2017-06-01

    Given the large number of bridges that currently have no instrumentation, there are obvious advantages in monitoring the condition of a bridge by analysing the response of a vehicle crossing it. As a result, the last two decades have seen a rise in the research attempting to solve the problem of identifying damage in a bridge from vehicle measurements. This paper examines the theoretical feasibility and practical limitations of a drive-by system in identifying damage associated to localised stiffness losses. First, the nature of the damage feature that is sought within the vehicle response needs to be characterized. For this purpose, the total vehicle response is considered to be made of 'static' and 'dynamic' components, and where the bridge has experienced a localised loss in stiffness, an additional 'damage' component. Understanding the nature of this 'damage' component is crucial to have an informed discussion on how damage can be identified and localised. Leveraging this new understanding, the authors propose a wavelet-based drive-by algorithm. By comparing the effect of the 'damage' component to other key effects defining the measurements such as 'vehicle speed', the 'road profile' and 'noise' on a wavelet contour plot, it is possible to establish if there is a frequency range where drive-by can be successful. The algorithm uses then specific frequency bands to improve the sensitivity to damage with respect to limitations imposed by Vehicle-Bridge vibrations. Recommendations on the selection of the mother wavelet and frequency band are provided. Finally, the paper discusses the impact of noise and road profile on the ability of the approach to identify damage and how periodic measurements can be effective at monitoring localised stiffness changes.

  10. Hospital Disaster Preparedness in Italy: a preliminary study utilizing the World Health Organization Hospital Emergency Response Evaluation Toolkit.

    PubMed

    Ingrassia, Pier L; Mangini, Marco; Azzaretto, Massimo; Ciaramitaro, Ilenia; Costa, Laura; Burkle, Frederick M; Della Corte, Francesco; Djalali, Ahmadreza

    2016-12-01

    Natural and human-initiated disasters are occurring with greater devastating consequences and increased frequency. During these events, hospitals have the burden to care for acutely ill and injured patients. The aim of this study was to evaluate the level of disaster preparedness of Italian hospitals. Site visits were conducted from January, 2014 to December, 2014. The hospital emergency response checklist, developed by the WHO, was used as an evaluation toolkit. It consists of 92 items classified as 9 key components, such as command and control, triage, and critical services. The status of each component was determined by consensus of 3 independent evaluators. The study selected 15 hospitals from different areas in Italy. Out of the 15 hospitals, 12 were considered to be at insufficients level of preparedness, only 3 were considered to have an effective level of preparedness. The average preparedness of all components were lower than the optimal level suggested by the WHO checklist. The study revealed that a large majority of Italian hospitals evaluated are not well prepared to manage potential disasters. Also, all important elements of hospital preparedness, such as the command system, surge capacity, and safety, were insufficiently implemented. Nationwide standards, guidelines and procedures are required to improve hospital disaster preparedness in Italy.

  11. Social Mobilization and Community Engagement Central to the Ebola Response in West Africa: Lessons for Future Public Health Emergencies.

    PubMed

    Gillespie, Amaya M; Obregon, Rafael; El Asawi, Rania; Richey, Catherine; Manoncourt, Erma; Joshi, Kshiitij; Naqvi, Savita; Pouye, Ade; Safi, Naqibullah; Chitnis, Ketan; Quereshi, Sabeeha

    2016-12-23

    Following the World Health Organization (WHO) declaration of a Public Health Emergency of International Concern regarding the Ebola outbreak in West Africa in July 2014, UNICEF was asked to co-lead, in coordination with WHO and the ministries of health of affected countries, the communication and social mobilization component-which UNICEF refers to as communication for development (C4D)-of the Ebola response. For the first time in an emergency setting, C4D was formally incorporated into each country's national response, alongside more typical components such as supplies and logistics, surveillance, and clinical care. This article describes the lessons learned about social mobilization and community engagement in the emergency response to the Ebola outbreak, with a particular focus on UNICEF's C4D work in Guinea, Liberia, and Sierra Leone. The lessons emerged through an assessment conducted by UNICEF using 4 methods: a literature review of key documents, meeting reports, and other articles; structured discussions conducted in June 2015 and October 2015 with UNICEF and civil society experts; an electronic survey, launched in October and November 2015, with staff from government, the UN, or any partner organization who worked on Ebola (N = 53); and key informant interviews (N = 5). After triangulating the findings from all data sources, we distilled lessons under 7 major domains: (1) strategy and decentralization: develop a comprehensive C4D strategy with communities at the center and decentralized programming to facilitate flexibility and adaptation to the local context; (2) coordination: establish C4D leadership with the necessary authority to coordinate between partners and enforce use of standard operating procedures as a central coordination and quality assurance tool; (3) entering and engaging communities: invest in key communication channels (such as radio) and trusted local community members; (4) messaging: adapt messages and strategies continually as patterns of the epidemic change over time; (5) partnerships: invest in strategic partnerships with community, religious leaders, journalists, radio stations, and partner organizations; (6) capacity building: support a network of local and international professionals with capacity for C4D who can be deployed rapidly; (7) data and performance monitoring: establish clear C4D process and impact indicators and strive for real-time data analysis and rapid feedback to communities and authorities to inform decision making. Ultimately, communication, community engagement, and social mobilization need to be formally placed within the global humanitarian response architecture with proper funding to effectively support future public health emergencies, which are as much a social as a health phenomenon. © Gillespie et al.

  12. Neem components as potential agents for cancer prevention and treatment

    PubMed Central

    Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

    2016-01-01

    Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment. PMID:25016141

  13. Molecular characterization and mRNA expression of two key enzymes of hypoxia-sensing pathways in eastern oysters Crassostrea virginica (Gmelin): Hypoxia-inducible factor α (HIF-α) and HIF-prolyl hydroxylase (PHD)

    PubMed Central

    Piontkivska, Helen; Chung, J. Sook; Ivanina, Anna V.; Sokolov, Eugene P.; Techa, Sirinart; Sokolova, Inna M.

    2010-01-01

    Oxygen homeostasis is crucial for development, survival and normal function of all metazoans. A family of transcription factors called hypoxia-inducible factors (HIF) is critical in mediating the adaptive responses to reduced oxygen availability. The HIF transcription factor consists of a constitutively expressed β subunit and an oxygen-dependent α subunit; the abundance of the latter determines the activity of HIF and is regulated by a family of O2- and Fe2+-dependent enzymes prolyl hydroxylases (PHDs). Currently very little is known about the function of this important pathway and the molecular structure of its key players in hypoxia-tolerant intertidal mollusks including oysters, which are among the animal champions of anoxic and hypoxic tolerance and thus can serve as excellent models to study the role of HIF cascade in adaptations to oxygen deficiency. We have isolated transcripts of two key components of the oxygen sensing pathway - the oxygen-regulated HIF-α subunit and PHD - from an intertidal mollusk, the eastern oyster Crassostrea virginica, and determined the transcriptional responses of these two genes to anoxia, hypoxia and cadmium (Cd) stress. HIF-α and PHD homologs from eastern oysters C. virginica show significant sequence similarity and share key functional domains with the earlier described isoforms from vertebrates and invertebrates. Phylogenetic analysis shows that genetic diversification of HIF and PHD isoforms occurred within the vertebrate lineage indicating functional diversification and specialization of the oxygen-sensing pathways in this group, which parallels situation observed for many other important genes. HIF-α and PHD homologs are broadly expressed at the mRNA level in different oyster tissues and show transcriptional responses to prolonged hypoxia in the gills consistent with their putative role in oxygen sensing and the adaptive response to hypoxia. Similarity in amino acid sequence, domain structure and transcriptional responses between HIF-α and PHD homologs from oysters and other invertebrate and vertebrate species implies the highly conserved functions of these genes throughout the evolutionary history of animals, in accordance with their critical role in oxygen sensing and homeostasis. PMID:21106446

  14. Insights into the role of neuronal glucokinase.

    PubMed

    De Backer, Ivan; Hussain, Sufyan S; Bloom, Stephen R; Gardiner, James V

    2016-07-01

    Glucokinase is a key component of the neuronal glucose-sensing mechanism and is expressed in brain regions that control a range of homeostatic processes. In this review, we detail recently identified roles for neuronal glucokinase in glucose homeostasis and counterregulatory responses to hypoglycemia and in regulating appetite. We describe clinical implications from these advances in our knowledge, especially for developing novel treatments for diabetes and obesity. Further research required to extend our knowledge and help our efforts to tackle the diabetes and obesity epidemics is suggested. Copyright © 2016 the American Physiological Society.

  15. Transient Negative Optical Nonlinearity of Indium Oxide Nanorod Arrays in the Full-Visible Range

    DOE PAGES

    Guo, Peijun; Chang, Robert P. H.; Schaller, Richard D.

    2017-06-09

    Dynamic control of the optical response of materials at visible wavelengths is key to future metamaterials and photonic integrated circuits. Here we demonstrate large amplitude, negative optical nonlinearity (Δ n from -0.05 to -0.09) of indium oxide nanorod arrays in the full-visible range. We experimentally quantify and theoretically calculate the optical nonlinearity, which arises from the modifications of interband optical transitions. Furthermore, the approach towards negative optical nonlinearity can be generalized to other transparent semiconductors and opens door to reconfigurable, sub-wavelength optical components.

  16. Bel Marin Keys Unit V Expansion of the Hamilton Wetland Restoration Project. Volume 3. Responses to Comments, Final Supplemental Environmental Impact Report/Environmental Impact Statement

    DTIC Science & Technology

    2003-04-01

    include a program for implementing new development and construction site storm water quality controls. The objective of this component is to ensure...impacts (see Storm Water Quality Control, below). The Regional Board has adopted U.S. EPA’s Clean Water Act Section 404(b)(1) "Guidelines for...other Waters of the State. Storm Water Quality Control Storm water is the major source of fresh water to creeks and waterways. Storm water quality is

  17. A national survey of cardiac rehabilitation services in New Zealand: 2015.

    PubMed

    Kira, Geoff; Doolan-Noble, Fiona; Humphreys, Grace; Williams, Gina; O'Shaughnessy, Helen; Devlin, Gerry

    2016-05-27

    Guidelines for cardiac rehabilitation (CR) programmes inform best practice. In Aotearoa NewZealand, little information exists about the structure and services provided by CR programmes and there is a poor understanding of how existing CR programmes are delivered with respect to evidence-based national guidelines. All 46 CR providers in New Zealand were invited to participate in a national survey in 2015. The survey sought information on the following: unit structure; referral processes; patient assessment; audit (including quality assurance activity); Phase 2 CR content; and support for special populations. Simple descriptive analysis of the responses was conducted, involving forming counts and percentages. Thirty-six distinct units completed the survey and 94% provided Phase 2. Assessment tools, Phase 2 educational components, and the methods of providing the exercise component varied. Most units audited their services, 25% audited their programme six-monthly or more frequently. Just over half of the units (56%) reported key performance indicators. The survey identified variations in delivery and content of CR in New Zealand, with poor understanding of the impact on patient outcomes. This is likely due to the absence of standardised audit practices and routine collection of key performance indicators on a national basis.

  18. Protection against oxidant-induced apoptosis by mitochondrial thioredoxin in SH-SY5Y neuroblastoma cells

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

    Chen Yan; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Atlanta, GA 30322; Yu Min

    2006-10-15

    Mitochondrial oxidative stress plays important roles in aging and age-related degenerative disorders. The newly identified mitochondrial thioredoxin (mtTrx; Trx2) is a key component of the mitochondrial antioxidant system which is responsible for the clearance of reactive intermediates and repairs proteins with oxidative damage. Here, we show that in cultured SH-SY5Y human neuroblastoma 1cells, overexpression of mtTrx inhibited apoptosis and loss of mitochondrial membrane potential induced by a chemical oxidant, tert-butylhydroperoxide (tBH). The effects of calcium ionophore (Br-A23187) were not affected by mtTrx, suggesting the protection was specific against oxidative injury. The mitochondrial glutathione pool was oxidized by tBH, and thismore » oxidation was not inhibited by increased mtTrx. Consequently, the antioxidant function of mtTrx is not redundant, but rather in addition, to that of GSH. Mutations of Cys90 and Cys93 to serines rendered mtTrx ineffective in protection against tBH-induced cytoxicity. These data indicate that mtTrx controls the mitochondrial redox status independently of GSH and is a key component of the defensive mechanism against oxidative stress in cultured neuronal cells.« less

  19. Improvements to the ShipIR/NTCS adaptive track gate algorithm and 3D flare particle model

    NASA Astrophysics Data System (ADS)

    Ramaswamy, Srinivasan; Vaitekunas, David A.; Gunter, Willem H.; February, Faith J.

    2017-05-01

    A key component in any image-based tracking system is the adaptive tracking algorithm used to segment the image into potential targets, rank-and-select the best candidate target, and gate the selected target to further improve tracker performance. Similarly, a key component in any soft-kill response to an incoming guided missile is the flare/chaff decoy used to distract or seduce the seeker homing system away from the naval platform. This paper describes the recent improvements to the naval threat countermeasure simulator (NTCS) of the NATO-standard ship signature model (ShipIR). Efforts to analyse and match the 3D flare particle model against actual IR measurements of the Chemring TALOS IR round resulted in further refinement of the 3D flare particle distribution. The changes in the flare model characteristics were significant enough to require an overhaul to the adaptive track gate (ATG) algorithm in the way it detects the presence of flare decoys and reacquires the target after flare separation. A series of test scenarios are used to demonstrate the impact of the new flare and ATG on IR tactics simulation.

  20. Systems Analysis Approach for the NASA Environmentally Responsible Aviation Project

    NASA Technical Reports Server (NTRS)

    Kimmel, William M.

    2011-01-01

    This conference paper describes the current systems analysis approach being implemented for the Environmentally Responsible Aviation Project within the Integrated Systems Research Program under the NASA Aeronautics Research Mission Directorate. The scope and purpose of these systems studies are introduced followed by a methodology overview. The approach involves both top-down and bottoms-up components to provide NASA s stakeholders with a rationale for the prioritization and tracking of a portfolio of technologies which enable the future fleet of aircraft to operate with a simultaneous reduction of aviation noise, emissions and fuel-burn impacts to our environment. Examples of key current results and relevant decision support conclusions are presented along with a forecast of the planned analyses to follow.

  1. Contribution of Kv7 channels to natriuretic peptide mediated vasodilation in normal and hypertensive rats.

    PubMed

    Stott, Jennifer B; Barrese, Vincenzo; Jepps, Thomas A; Leighton, Emma V; Greenwood, Iain A

    2015-03-01

    The Kv7 family of voltage-gated potassium channels are expressed within the vasculature where they are key regulators of vascular tone and mediate cAMP-linked endogenous vasodilator responses, a pathway that is compromised in hypertension. However, the role of Kv7 channels in non-cAMP-linked vasodilator pathways has not been investigated. Natriuretic peptides are potent vasodilators, which operate primarily through the activation of a cGMP-dependent signaling pathway. This study investigated the putative role of Kv7 channels in natriuretic peptide-dependent relaxations in the vasculature of normal and hypertensive animals. Relaxant responses of rat aorta to both atrial and C-type natriuretic peptides and the nitric oxide donor sodium nitroprusside were impaired by the Kv7 blocker linopirdine (10 μmol/L) but not by the Kv7.1-specific blocker HMR1556 (10 μmol/L) and other K(+) channel blockers. In contrast, only the atrial natriuretic peptide response was sensitive to linopirdine in the renal artery. These Kv7-mediated responses were attenuated in arteries from hypertensive rats. Quantitative polymerase chain reaction showed that A- and B-type natriuretic peptide receptors were expressed at high levels in the aorta and renal artery from normal and spontaneously hypertensive rats. This study provides the first evidence that natriuretic peptide responses are impaired in hypertension and that recruitment of Kv7 channels is a key component of natriuretic peptide-dependent vasodilations. © 2014 American Heart Association, Inc.

  2. The associative relation underlying autoshaping in the pigeon1

    PubMed Central

    Woodruff, Guy; Williams, D. R.

    1976-01-01

    Fifteen pigeons were exposed to either response-independent or response-dependent schedules of water reinforcement, whereby water was injected directly into the unrestrained pigeons' mandibles. Key-contact responses were released by a lighted key correlated with water, but not by a lighted key uncorrelated with water. A negative response-reinforcer contingency suppressed autoshaped key-contact responses, resulting in responding directed away from the lighted key. In all pigeons, water injected directly into the mandibles elicited a consummatory fixed-action pattern of “mumbling” and swallowing. The lighted key correlated with water released a broader set of both appetitive and consummatory responses: approach to the lighted key, “bowing”, “rooting”, “mumbling”, and swallowing. Key-contact responses were “rooting” and “mumbling” motions of the beak on the surface of the key. Views of autoshaping based on stimulus substitution or stimulus surrogation do not fully explain the origin of autoshaped responses not previously elicited by the reinforcer. The present findings are consonant with views of conditioning that emphasize the large degree of biological pre-organization in conditioned response patterns, and the importance of associative factors in the control of such patterns. PMID:16811924

  3. Could Notch signaling pathway be a potential therapeutic option in renal diseases?

    PubMed

    Marquez-Exposito, Laura; Cantero-Navarro, Elena; Lavoz, Carolina; Fierro-Fernández, Marta; Poveda, Jonay; Rayego-Mateos, Sandra; Rodrigues-Diez, Raúl R; Morgado-Pascual, José Luis; Orejudo, Macarena; Mezzano, Sergio; Ruiz-Ortega, Marta

    2018-02-10

    Notch pathway regulates key processes in the kidney, involved in embryonic development and tissue damage. In many human chronic renal diseases a local activation of Notch pathway has been described, suggesting that several components of Notch pathway could be considered as biomarkers of renal damage. Experimental studies by genetic modulation of Notch components or pharmacological approaches by γ-secretase inhibitors have demonstrated the role of this pathway in renal regeneration renal, podocyte apoptosis, proliferation and fibroblasts activation, and induction of epithelial to mesenchymal transition of tubular epithelial cells. Recent studies suggest an interaction between Notch and NF-κB pathway involved in the regulation of renal inflammatory process. On the other hand, there are some miRNAs that could regulate Notch components and down-stream responses. All these data suggest that Notch blockade could be a novel therapeutic option for renal diseases. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  4. Stimulation of complement component C3 synthesis in macrophagelike cell lines by group B streptococci.

    PubMed Central

    Goodrum, K J

    1987-01-01

    Complement levels and complement activation are key determinants in streptococcus-induced inflammatory responses. Activation of macrophage functions, such as complement synthesis, by group B streptococci (GBS) was examined as a possible component of GBS-induced chronic inflammation. Using an enzyme-linked immunosorbent assay, secreted C3 from mouse macrophagelike cell lines (PU5-1.8 and J774A.1) was monitored after cultivation with GBS. Whole, heat-killed GBS (1 to 10 CFU per macrophage) of both type Ia and III strains induced 25 to 300% increases in secreted C3 in both cell lines after a 24-h cultivation. GBS-treated cell lines exhibited increases in secreted lysozyme (10%) and in cellular protein (25 to 50%). Inhibition of macrophage phagocytosis by cytochalasin B inhibited GBS stimulation of C3. Purified cell walls of GBS type III strain 603-79 (1 to 10 micrograms/ml) also enhanced C3 synthesis. Local enhancement of macrophage C3 production by ingested streptococci or by persistent cell wall antigens may serve to promote chronic inflammatory responses. PMID:3552987

  5. Is lactate an undervalued functional component of fermented food products?

    PubMed Central

    Garrote, Graciela L.; Abraham, Analía G.; Rumbo, Martín

    2015-01-01

    Although it has been traditionally regarded as an intermediate of carbon metabolism and major component of fermented dairy products contributing to organoleptic and antimicrobial properties of food, there is evidence gathered in recent years that lactate has bioactive properties that may be responsible of broader properties of functional foods. Lactate can regulate critical functions of several key players of the immune system such as macrophages and dendritic cells, being able to modulate inflammatory activation of epithelial cells as well. Intraluminal levels of lactate derived from fermentative metabolism of lactobacilli have been shown to modulate inflammatory environment in intestinal mucosa. The molecular mechanisms responsible to these functions, including histone deacetylase dependent-modulation of gene expression and signaling through G-protein coupled receptors have started to be described. Since lactate is a major fermentation product of several bacterial families with probiotic properties, we here propose that it may contribute to some of the properties attributed to these microorganisms and in a larger view, to the properties of food products fermented by lactic acid bacteria. PMID:26150815

  6. The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways.

    PubMed

    Derous, Davina; Mitchell, Sharon E; Green, Cara L; Chen, Luonan; Han, Jing-Dong J; Wang, Yingchun; Promislow, Daniel E L; Lusseau, David; Speakman, John R; Douglas, Alex

    2016-04-01

    Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti-ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin-like growth factor 1 (IGF-1), insulin, and tumor necrosis factor alpha (TNF-α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF-α, leptin and IGF-1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes.

  7. The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways

    PubMed Central

    Green, Cara L.; Chen, Luonan; Han, Jing‐Dong J.; Wang, Yingchun; Promislow, Daniel E.L.; Lusseau, David; Speakman, John R.; Douglas, Alex

    2016-01-01

    Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti‐ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin‐like growth factor 1 (IGF‐1), insulin, and tumor necrosis factor alpha (TNF‐α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF‐α, leptin and IGF‐1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes. PMID:26945906

  8. Nrf2-p62 autophagy pathway and its response to oxidative stress in hepatocellular carcinoma.

    PubMed

    Bartolini, Desirée; Dallaglio, Katiuscia; Torquato, Pierangelo; Piroddi, Marta; Galli, Francesco

    2018-03-01

    Deregulation of autophagy is proposed to play a key pathogenic role in hepatocellular carcinoma (HCC), the most common primary malignancy of the liver and the third leading cause of cancer death. Autophagy is an evolutionarily conserved catabolic process activated to degrade and recycle cell's components. Under stress conditions, such as oxidative stress and nutrient deprivation, autophagy is an essential survival pathway that operates in harmony with other stress response pathways. These include the redox-sensitive transcription complex Nrf2-Keap1 that controls groups of genes with roles in detoxification and antioxidant processes, intermediary metabolism, and cell cycle regulation. Recently, a functional association between a dysfunctional autophagy and Nrf2 pathway activation has been identified in HCC. This appears to occur through the physical interaction of the autophagy adaptor p62 with the Nrf2 inhibitor Keap1, thus leading to increased stabilization and transcriptional activity of Nrf2, a key event in reprogramming metabolic and stress response pathways of proliferating hepatocarcinoma cells. These emerging molecular mechanisms and the therapeutic perspective of targeting Nrf2-p62 interaction in HCC are discussed in this paper along with the prognostic value of autophagy in this type of cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Thermoelectric-Driven Sustainable Sensing and Actuation Systems for Fault-Tolerant Nuclear Incidents

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

    Longtin, Jon

    2016-02-08

    The Fukushima Daiichi nuclear incident in March 2011 represented an unprecedented stress test on the safety and backup systems of a nuclear power plant. The lack of reliable information from key components due to station blackout was a serious setback, leaving sensing, actuation, and reporting systems unable to communicate, and safety was compromised. Although there were several independent backup power sources for required safety function on site, ultimately the batteries were drained and the systems stopped working. If, however, key system components were instrumented with self-powered sensing and actuation packages that could report indefinitely on the status of the system,more » then critical system information could be obtained while providing core actuation and control during off-normal status for as long as needed. This research project focused on the development of such a self-powered sensing and actuation system. The electrical power is derived from intrinsic heat in the reactor components, which is both reliable and plentiful. The key concept was based around using thermoelectric generators that can be integrated directly onto key nuclear components, including pipes, pump housings, heat exchangers, reactor vessels, and shielding structures, as well as secondary-side components. Thermoelectric generators are solid-state devices capable of converting heat directly into electricity. They are commercially available technology. They are compact, have no moving parts, are silent, and have excellent reliability. The key components to the sensor package include a thermoelectric generator (TEG), microcontroller, signal processing, and a wireless radio package, environmental hardening to survive radiation, flooding, vibration, mechanical shock (explosions), corrosion, and excessive temperature. The energy harvested from the intrinsic heat of reactor components can be then made available to power sensors, provide bi-directional communication, recharge batteries for other safety systems, etc. Such an approach is intrinsically fault tolerant: in the event that system temperatures increase, the amount of available energy will increase, which will make more power available for applications. The system can also be used during normal conditions to provide enhanced monitoring of key system components.« less

  10. The Neuroendocrinology of the Microbiota-Gut-Brain Axis: A Behavioural Perspective.

    PubMed

    Cussotto, Sofia; Sandhu, Kiran V; Dinan, Timothy G; Cryan, John F

    2018-05-10

    The human gut harbours trillions of symbiotic bacteria that play a key role in programming different aspects of host physiology in health and disease. These intestinal microbes are also key components of the gut-brain axis, the bidirectional communication pathway between the gut and the central nervous system (CNS). In addition, the CNS is closely interconnected with the endocrine system to regulate many physiological processes. An expanding body of evidence is supporting the notion that gut microbiota modifications and/or manipulations may also play a crucial role in the manifestation of specific behavioural responses regulated by neuroendocrine pathways. In this review, we will focus on how the intestinal microorganisms interact with elements of the host neuroendocrine system to modify behaviours relevant to stress, eating behaviour, sexual behaviour, social behaviour, cognition and addiction. Copyright © 2018. Published by Elsevier Inc.

  11. Early warning systems and rapid response to the deteriorating patient in hospital: A realist evaluation.

    PubMed

    McGaughey, Jennifer; O'Halloran, Peter; Porter, Sam; Trinder, John; Blackwood, Bronagh

    2017-12-01

    To test the Rapid Response Systems programme theory against actual practice components of the Rapid Response Systems implemented to identify those contexts and mechanisms which have an impact on the successful achievement of desired outcomes in practice. Rapid Response Systems allow deteriorating patients to be recognized using Early Warning Systems, referred early via escalation protocols and managed at the bedside by competent staff. Realist evaluation. The research design was an embedded multiple case study approach of four wards in two hospitals in Northern Ireland which followed the principles of Realist Evaluation. We used various mixed methods including individual and focus group interviews, observation of nursing practice between June-November 2010 and document analysis of Early Warning Systems audit data between May-October 2010 and hospital acute care training records over 4.5 years from 2003-2008. Data were analysed using NiVivo8 and SPPS. A cross-case analysis highlighted similar patterns of factors which enabled or constrained successful recognition, referral and response to deteriorating patients in practice. Key enabling factors were the use of clinical judgement by experienced nurses and the empowerment of nurses as a result of organizational change associated with implementation of Early Warning System protocols. Key constraining factors were low staffing and inappropriate skill mix levels, rigid implementation of protocols and culturally embedded suboptimal communication processes. Successful implementation of Rapid Response Systems was dependent on adopting organizational and cultural changes that facilitated staff empowerment, flexible implementation of protocols and ongoing experiential learning. © 2017 John Wiley & Sons Ltd.

  12. Gravitropism and mechanical signaling in plants.

    PubMed

    Toyota, Masatsugu; Gilroy, Simon

    2013-01-01

    Mechanical stress is a critical signal affecting morphogenesis and growth and is caused by a large variety of environmental stimuli such as touch, wind, and gravity in addition to endogenous forces generated by growth. On the basis of studies dating from the early 19th century, the plant mechanical sensors and response components related to gravity can be divided into two types in terms of their temporal character: sensors of the transient stress of reorientation (phasic signaling) and sensors capable of monitoring and responding to the extended, continuous gravitropic signal for the duration of the tropic growth response (tonic signaling). In the case of transient stress, changes in the concentrations of ions in the cytoplasm play a central role in mechanosensing and are likely a key component of initial gravisensing. Potential candidates for mechanosensitive channels have been identified in Arabidopsis thaliana and may provide clues to these rapid, ionic gravisensing mechanisms. Continuous mechanical stress, on the other hand, may be sensed by other mechanisms in addition to the rapidly adapting mechnaosensitive channels of the phasic system. Sustaining such long-term responses may be through a network of biochemical signaling cascades that would therefore need to be maintained for the many hours of the growth response once they are triggered. However, classical physiological analyses and recent simulation studies also suggest involvement of the cytoskeleton in sensing/responding to long-term mechanoresponse independently of the biochemical signaling cascades triggered by initial graviperception events.

  13. Special Education Law: Illustrative Basics and Nuances of Key IDEA Components

    ERIC Educational Resources Information Center

    Zirkel, Perry A.

    2015-01-01

    Intended as professional development for both new and experienced special educators, this article provides both the basic requirements and nuanced issues for foundational, successive, and overlapping key components under the Individuals With Disabilities Education Act (IDEA): (a) child find, (b) eligibility, and (c) free appropriate public…

  14. Childhood Immunization: A Key Component of Early Childhood Development

    ERIC Educational Resources Information Center

    Messonnier, Nancy

    2017-01-01

    Physical health is a key component of early childhood development and school readiness. By keeping children healthy and decreasing the chances of disease outbreaks, immunizations help early childhood programs create a safe environment for children. While overall vaccination rates are high nationally for most vaccines routinely recommended for…

  15. A Connected History of Health and Education: Learning Together toward a Better City

    ERIC Educational Resources Information Center

    Howard, Joanne; Howard, Diane; Dotson, Ebbin

    2015-01-01

    The infrastructure, financial, and human resource histories of health and education are offered as key components of future strategic planning initiatives in learning cities, and 10 key components of strategic planning initiatives designed to enhance the health and wealth of citizens of learning cities are discussed.

  16. Concurrent schedules: Effects of time- and response-allocation constraints

    PubMed Central

    Davison, Michael

    1991-01-01

    Five pigeons were trained on concurrent variable-interval schedules arranged on two keys. In Part 1 of the experiment, the subjects responded under no constraints, and the ratios of reinforcers obtainable were varied over five levels. In Part 2, the conditions of the experiment were changed such that the time spent responding on the left key before a subsequent changeover to the right key determined the minimum time that must be spent responding on the right key before a changeover to the left key could occur. When the left key provided a higher reinforcer rate than the right key, this procedure ensured that the time allocated to the two keys was approximately equal. The data showed that such a time-allocation constraint only marginally constrained response allocation. In Part 3, the numbers of responses emitted on the left key before a changeover to the right key determined the minimum number of responses that had to be emitted on the right key before a changeover to the left key could occur. This response constraint completely constrained time allocation. These data are consistent with the view that response allocation is a fundamental process (and time allocation a derivative process), or that response and time allocation are independently controlled, in concurrent-schedule performance. PMID:16812632

  17. Responses of soil physical and chemical properties to karst rocky desertification evolution in typical karst valley area

    NASA Astrophysics Data System (ADS)

    Chen, Fei; Zhou, Dequan; Bai, Xiaoyong; zeng, Cheng; Xiao, Jianyong; Qian, Qinghuan; Luo, Guangjie

    2018-01-01

    In order to reveal the differences of soil physical and chemical properties and their response mechanism to the evolution of KRD. The characteristics of soil physical and chemical properties of different grades of KRD were studied by field sampling method to research different types of KRD in the typical karst valley of southern China. Instead of using space of time, to explore the response and the mechanisms of the soil physical and chemical properties at the different evolution process. The results showed that: (1) There were significant differences in organic matter, pH, total nitrogen, total phosphorus, total potassium, sediment concentration, clay content and AWHC in different levels of KRD environment. However, these indicators are not with increasing desertification degree has been degraded, but improved after a first degradation trends; (2) The correlation analysis showed that soil organic matter, acid, alkali, total nitrogen, total phosphorus, total potassium and clay contents were significantly correlated with other physical and chemical factors. They are the key factors of soil physical and chemical properties, play a key role in improving soil physical and chemical properties and promoting nutrient cycling; (3) The principal component analysis showed that the cumulative contribution rate of organic matter, pH, total nitrogen, total phosphorus, total potassium and sediment concentration was 80.26%, which was the key index to evaluate rocky desertification degree based on soil physical and chemical properties. The results have important theoretical and practical significance for the protection and restoration of rocky desertification ecosystem in southwest China.

  18. Multicomponent reactions provide key molecules for secret communication.

    PubMed

    Boukis, Andreas C; Reiter, Kevin; Frölich, Maximiliane; Hofheinz, Dennis; Meier, Michael A R

    2018-04-12

    A convenient and inherently more secure communication channel for encoding messages via specifically designed molecular keys is introduced by combining advanced encryption standard cryptography with molecular steganography. The necessary molecular keys require large structural diversity, thus suggesting the application of multicomponent reactions. Herein, the Ugi four-component reaction of perfluorinated acids is utilized to establish an exemplary database consisting of 130 commercially available components. Considering all permutations, this combinatorial approach can unambiguously provide 500,000 molecular keys in only one synthetic procedure per key. The molecular keys are transferred nondigitally and concealed by either adsorption onto paper, coffee, tea or sugar as well as by dissolution in a perfume or in blood. Re-isolation and purification from these disguises is simplified by the perfluorinated sidechains of the molecular keys. High resolution tandem mass spectrometry can unequivocally determine the molecular structure and thus the identity of the key for a subsequent decryption of an encoded message.

  19. 2006 Precision Strike Technology Symposium

    DTIC Science & Technology

    2006-10-19

    s Navy Unique Joint system 14 A/C Unique Components Framework JMPS Common Components Crypto Key GCCS-M Interface Carrier Intel Feed Carrier...210 GPS Prediction CUPC GPS Crypto Key TAMMAC SLAM-ER GPS Almanac ETIRMS PMA-281 NGMS PMA-209 Boeing PMA-201 Raytheon ESC (USAF) Hill AFB PMA-234 PMA...242 F/A-18 UPC GPS Prediction CUPC GPS Crypto Key TAMMAC SLAM-ER GPS Almanac HARM WASP Framework ARC-210 ETIRMS PMA-281 Integration/Test/ Support TLAM

  20. Secure content objects

    DOEpatents

    Evans, William D [Cupertino, CA

    2009-02-24

    A secure content object protects electronic documents from unauthorized use. The secure content object includes an encrypted electronic document, a multi-key encryption table having at least one multi-key component, an encrypted header and a user interface device. The encrypted document is encrypted using a document encryption key associated with a multi-key encryption method. The encrypted header includes an encryption marker formed by a random number followed by a derivable variation of the same random number. The user interface device enables a user to input a user authorization. The user authorization is combined with each of the multi-key components in the multi-key encryption key table and used to try to decrypt the encrypted header. If the encryption marker is successfully decrypted, the electronic document may be decrypted. Multiple electronic documents or a document and annotations may be protected by the secure content object.

  1. Cryptochrome 1 interacts with PIF4 to regulate high temperature-mediated hypocotyl elongation in response to blue light.

    PubMed

    Ma, Dingbang; Li, Xu; Guo, Yongxia; Chu, Jingfang; Fang, Shuang; Yan, Cunyu; Noel, Joseph P; Liu, Hongtao

    2016-01-05

    Cryptochrome 1 (CRY1) is a blue light receptor that mediates primarily blue-light inhibition of hypocotyl elongation. Very little is known of the mechanisms by which CRY1 affects growth. Blue light and temperature are two key environmental signals that profoundly affect plant growth and development, but how these two abiotic factors integrate remains largely unknown. Here, we show that blue light represses high temperature-mediated hypocotyl elongation via CRY1. Furthermore, CRY1 interacts directly with PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) in a blue light-dependent manner to repress the transcription activity of PIF4. CRY1 represses auxin biosynthesis in response to elevated temperature through PIF4. Our results indicate that CRY1 signal by modulating PIF4 activity, and that multiple plant photoreceptors [CRY1 and PHYTOCHROME B (PHYB)] and ambient temperature can mediate morphological responses through the same signaling component-PIF4.

  2. Bacterial RNA induces myocyte cellular dysfunction through the activation of PKR

    PubMed Central

    Bleiblo, Farag; Michael, Paul; Brabant, Danielle; Ramana, Chilakamarti V.; Tai, TC; Saleh, Mazen; Parrillo, Joseph E.; Kumar, Anand

    2012-01-01

    Severe sepsis and the ensuing septic shock are serious life threatening conditions. These diseases are triggered by the host's over exuberant systemic response to the infecting pathogen. Several surveillance mechanisms have evolved to discriminate self from foreign RNA and accordingly trigger effective cellular responses to target the pathogenic threats. The RNA-dependent protein kinase (PKR) is a key component of the cytoplasmic RNA sensors involved in the recognition of viral double-stranded RNA (dsRNA). Here, we identify bacterial RNA as a distinct pathogenic pattern recognized by PKR. Our results indicate that natural RNA derived from bacteria directly binds to and activates PKR. We further show that bacterial RNA induces human cardiac myocyte apoptosis and identify the requirement for PKR in mediating this response. In addition to bacterial immunity, the results presented here may also have implications in cardiac pathophysiology. PMID:22833816

  3. Changing partners at the dance

    PubMed Central

    Kallal, Lara E.; Biron, Christine A.

    2013-01-01

    Differential use of cellular and molecular components shapes immune responses, but understanding of how these are regulated to promote defense and health during infections is still incomplete. Examples include signaling from members of the Janus activated kinase-signal transducer and activator of transcription (JAK-STAT) cytokine family. Following receptor stimulation, individual JAK-STAT cytokines have preferences for particular key STAT molecules to lead to specific cellular responses. Certain of these cytokines, however, can conditionally activate alternative STATs as well as elicit pleiotropic and paradoxical effects. Studies examining basal and infection conditions are revealing intrinsic and induced cellular differences in various intracellular STAT concentrations to control the biological consequences of cytokine exposure. The system can be likened to changing partners at a dance based on competition and relative availability, and sets a framework for understanding the particular conditions promoting subset biological functions of cytokines as needed during evolving immune responses to infections. PMID:24058795

  4. Genome-Wide Identification of Binding Sites Defines Distinct Functions for Caenorhabditis elegans PHA-4/FOXA in Development and Environmental Response

    PubMed Central

    Zhong, Mei; Niu, Wei; Lu, Zhi John; Sarov, Mihail; Murray, John I.; Janette, Judith; Raha, Debasish; Sheaffer, Karyn L.; Lam, Hugo Y. K.; Preston, Elicia; Slightham, Cindie; Hillier, LaDeana W.; Brock, Trisha; Agarwal, Ashish; Auerbach, Raymond; Hyman, Anthony A.; Gerstein, Mark; Mango, Susan E.; Kim, Stuart K.; Waterston, Robert H.; Reinke, Valerie; Snyder, Michael

    2010-01-01

    Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We describe and validate this strategy, and apply it to the transcription factor PHA-4, which plays critical roles in organ development and other cellular processes. We identified thousands of binding sites for PHA-4 during formation of the embryonic pharynx, and also found a role for this factor during the starvation response. Many binding sites were found to shift dramatically between embryos and starved larvae, from developmentally regulated genes to genes involved in metabolism. These results indicate distinct roles for this regulator in two different biological processes and demonstrate the versatility of transcription factors in mediating diverse biological roles. PMID:20174564

  5. Decision-making in the adolescent brain.

    PubMed

    Blakemore, Sarah-Jayne; Robbins, Trevor W

    2012-09-01

    Adolescence is characterized by making risky decisions. Early lesion and neuroimaging studies in adults pointed to the ventromedial prefrontal cortex and related structures as having a key role in decision-making. More recent studies have fractionated decision-making processes into its various components, including the representation of value, response selection (including inter-temporal choice and cognitive control), associative learning, and affective and social aspects. These different aspects of decision-making have been the focus of investigation in recent studies of the adolescent brain. Evidence points to a dissociation between the relatively slow, linear development of impulse control and response inhibition during adolescence versus the nonlinear development of the reward system, which is often hyper-responsive to rewards in adolescence. This suggests that decision-making in adolescence may be particularly modulated by emotion and social factors, for example, when adolescents are with peers or in other affective ('hot') contexts.

  6. Annular Mode Dynamics: Eddy Feedbacks and the Underlying Mechanisms

    NASA Astrophysics Data System (ADS)

    Hassanzadeh, P.; Ma, D.; Kuang, Z.

    2017-12-01

    Annular modes are the leading modes the extratropical circulation variability in both hemispheres on intraseasonal to interannual timescales. Temporal persistence and an equivalent-barotropic dipolar wind anomaly are the key spatio-temporal characteristics of the annular modes. The potential source(s) of this persistence, and in particular, whether there is a contribution from a positive eddy-jet feedback, are still unclear (e.g., Lorenz and Hartmann, 2001; Byrne et al., 2016). The mechanism of this feedback, and how it depends on processes such as surface friction, is also not well understood (e.g., Robinson, 2000; Gerber et al., 2007). In this study, we utilize the recently calculated Linear Response Function (LRF) of an idealized GCM (Hassanzadeh and Kuang, 2016). The LRF enables us to accurately calculate the response of eddy momentum/heat fluxes to the zonal-mean zonal wind and temperature anomalies of the annular mode. Using this information: 1) We confirm the existence of a positive eddy-jet feedback in the annular mode of the idealized GCM and accurately quantify the magnitude of this feedback; 2) We quantify the contribution of key processes (e.g., eddy momentum/heat fluxes and surface friction) to the annular mode dynamics in the idealized GCM. We show that as proposed by Robinson (2000), the baroclinic component of the annular mode and surface friction are essential for the positive eddy-jet feedback. Results show that this feedback increases the persistence of the annular mode by a factor of two. We also show that the barotropic component of the annular mode alone does not lead to persistence. In fact, the eddy-jet feedback for the barotropic component is negative because of the dominance of the barotropic governor effect. 3) Using the results of 1, we evaluate the underlying assumptions and accuracy of the statistical methods previously developed for quantifying the eddy-jet feedback (Lorenz and Hartmann, 2001; Simpson et al., 2013) and introduce a new statistical method that shows superior accuracy. We apply the new method to reanalysis data to quantify the eddy-jet feedback for the Southern Annular Mode. The key findings of 1-3 and their implications for our understanding of the annular mode dynamics will be discussed in this presentation.

  7. Nitric Oxide Regulates Protein Methylation during Stress Responses in Plants.

    PubMed

    Hu, Jiliang; Yang, Huanjie; Mu, Jinye; Lu, Tiancong; Peng, Juli; Deng, Xian; Kong, Zhaosheng; Bao, Shilai; Cao, Xiaofeng; Zuo, Jianru

    2017-08-17

    Methylation and nitric oxide (NO)-based S-nitrosylation are highly conserved protein posttranslational modifications that regulate diverse biological processes. In higher eukaryotes, PRMT5 catalyzes Arg symmetric dimethylation, including key components of the spliceosome. The Arabidopsis prmt5 mutant shows severe developmental defects and impaired stress responses. However, little is known about the mechanisms regulating the PRMT5 activity. Here, we report that NO positively regulates the PRMT5 activity through S-nitrosylation at Cys-125 during stress responses. In prmt5-1 plants, a PRMT5 C125S transgene, carrying a non-nitrosylatable mutation at Cys-125, fully rescues the developmental defects, but not the stress hypersensitive phenotype and the responsiveness to NO during stress responses. Moreover, the salt-induced Arg symmetric dimethylation is abolished in PRMT5 C125S /prmt5-1 plants, correlated to aberrant splicing of pre-mRNA derived from a stress-related gene. These findings define a mechanism by which plants transduce stress-triggered NO signal to protein methylation machinery through S-nitrosylation of PRMT5 in response to environmental alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Unbiased RNAi screen for hepcidin regulators links hepcidin suppression to proliferative Ras/RAF and nutrient-dependent mTOR signaling

    PubMed Central

    Mleczko-Sanecka, Katarzyna; Roche, Franziska; Rita da Silva, Ana; Call, Debora; D’Alessio, Flavia; Ragab, Anan; Lapinski, Philip E.; Ummanni, Ramesh; Korf, Ulrike; Oakes, Christopher; Damm, Georg; D’Alessandro, Lorenza A.; Klingmüller, Ursula; King, Philip D.; Boutros, Michael; Hentze, Matthias W.

    2014-01-01

    The hepatic hormone hepcidin is a key regulator of systemic iron metabolism. Its expression is largely regulated by 2 signaling pathways: the “iron-regulated” bone morphogenetic protein (BMP) and the inflammatory JAK-STAT pathways. To obtain broader insights into cellular processes that modulate hepcidin transcription and to provide a resource to identify novel genetic modifiers of systemic iron homeostasis, we designed an RNA interference (RNAi) screen that monitors hepcidin promoter activity after the knockdown of 19 599 genes in hepatocarcinoma cells. Interestingly, many of the putative hepcidin activators play roles in signal transduction, inflammation, or transcription, and affect hepcidin transcription through BMP-responsive elements. Furthermore, our work sheds light on new components of the transcriptional machinery that maintain steady-state levels of hepcidin expression and its responses to the BMP- and interleukin-6–triggered signals. Notably, we discover hepcidin suppression mediated via components of Ras/RAF MAPK and mTOR signaling, linking hepcidin transcriptional control to the pathways that respond to mitogen stimulation and nutrient status. Thus using a combination of RNAi screening, reverse phase protein arrays, and small molecules testing, we identify links between the control of systemic iron homeostasis and critical liver processes such as regeneration, response to injury, carcinogenesis, and nutrient metabolism. PMID:24385536

  9. Optimization of Polygalacturonase Production from a Newly Isolated Thalassospira frigidphilosprofundus to Use in Pectin Hydrolysis: Statistical Approach

    PubMed Central

    Rekha, V. P. B.; Ghosh, Mrinmoy; Adapa, Vijayanand; Oh, Sung-Jong; Pulicherla, K. K.; Sambasiva Rao, K. R. S.

    2013-01-01

    The present study deals with the production of cold active polygalacturonase (PGase) by submerged fermentation using Thalassospira frigidphilosprofundus, a novel species isolated from deep waters of Bay of Bengal. Nonlinear models were applied to optimize the medium components for enhanced production of PGase. Taguchi orthogonal array design was adopted to evaluate the factors influencing the yield of PGase, followed by the central composite design (CCD) of response surface methodology (RSM) to identify the optimum concentrations of the key factors responsible for PGase production. Data obtained from the above mentioned statistical experimental design was used for final optimization study by linking the artificial neural network and genetic algorithm (ANN-GA). Using ANN-GA hybrid model, the maximum PGase activity (32.54 U/mL) was achieved at the optimized concentrations of medium components. In a comparison between the optimal output of RSM and ANN-GA hybrid, the latter favored the production of PGase. In addition, the study also focused on the determination of factors responsible for pectin hydrolysis by crude pectinase extracted from T. frigidphilosprofundus through the central composite design. Results indicated 80% degradation of pectin in banana fiber at 20°C in 120 min, suggesting the scope of cold active PGase usage in the treatment of raw banana fibers. PMID:24455722

  10. Optimization of polygalacturonase production from a newly isolated Thalassospira frigidphilosprofundus to use in pectin hydrolysis: statistical approach.

    PubMed

    Rekha, V P B; Ghosh, Mrinmoy; Adapa, Vijayanand; Oh, Sung-Jong; Pulicherla, K K; Sambasiva Rao, K R S

    2013-01-01

    The present study deals with the production of cold active polygalacturonase (PGase) by submerged fermentation using Thalassospira frigidphilosprofundus, a novel species isolated from deep waters of Bay of Bengal. Nonlinear models were applied to optimize the medium components for enhanced production of PGase. Taguchi orthogonal array design was adopted to evaluate the factors influencing the yield of PGase, followed by the central composite design (CCD) of response surface methodology (RSM) to identify the optimum concentrations of the key factors responsible for PGase production. Data obtained from the above mentioned statistical experimental design was used for final optimization study by linking the artificial neural network and genetic algorithm (ANN-GA). Using ANN-GA hybrid model, the maximum PGase activity (32.54 U/mL) was achieved at the optimized concentrations of medium components. In a comparison between the optimal output of RSM and ANN-GA hybrid, the latter favored the production of PGase. In addition, the study also focused on the determination of factors responsible for pectin hydrolysis by crude pectinase extracted from T. frigidphilosprofundus through the central composite design. Results indicated 80% degradation of pectin in banana fiber at 20 °C in 120 min, suggesting the scope of cold active PGase usage in the treatment of raw banana fibers.

  11. Electrodynamics of the nodal metal state in weakly doped high- Tc cuprates

    NASA Astrophysics Data System (ADS)

    Lee, Y. S.; Segawa, Kouji; Li, Z. Q.; Padilla, W. J.; Dumm, M.; Dordevic, S. V.; Homes, C. C.; Ando, Yoichi; Basov, D. N.

    2005-08-01

    We report on the detailed analysis of the infrared (IR) conductivity of two prototypical high- Tc systems YBa2Cu3Oy and La2-xSrxCuO4 throughout the complex phase diagram of these compounds. Our focus in this work is to thoroughly document the electromagnetic response of the nodal metal state which is initiated with only a few holes doped in parent antiferromagnetic systems and extends up to the pseudogap boundary in the phase diagram. The key signature of the nodal metal is the two-component conductivity: the Drude mode at low energies followed by a resonance in mid-IR. The Drude component can be attributed to the response of coherent quasiparticles residing on the Fermi arcs detected in photoemission experiments. The microscopic origin of the mid-IR band is yet to be understood. A combination of transport and IR data uncovers fingerprints of the Fermi liquid behavior in the response of the nodal metal. The comprehensive nature of the data sets presented in this work allows us to critically re-evaluate common approaches to the interpretation of the optical data. Specifically we re-examine the role of magnetic excitations in generating electronic self-energy effects through the analysis of the IR data in a high magnetic field.

  12. Role of Silicon on Plant–Pathogen Interactions

    PubMed Central

    Wang, Min; Gao, Limin; Dong, Suyue; Sun, Yuming; Shen, Qirong; Guo, Shiwei

    2017-01-01

    Although silicon (Si) is not recognized as an essential element for general higher plants, it has beneficial effects on the growth and production of a wide range of plant species. Si is known to effectively mitigate various environmental stresses and enhance plant resistance against both fungal and bacterial pathogens. In this review, the effects of Si on plant–pathogen interactions are analyzed, mainly on physical, biochemical, and molecular aspects. In most cases, the Si-induced biochemical/molecular resistance during plant–pathogen interactions were dominated as joint resistance, involving activating defense-related enzymes activates, stimulating antimicrobial compound production, regulating the complex network of signal pathways, and activating of the expression of defense-related genes. The most previous studies described an independent process, however, the whole plant resistances were rarely considered, especially the interaction of different process in higher plants. Si can act as a modulator influencing plant defense responses and interacting with key components of plant stress signaling systems leading to induced resistance. Priming of plant defense responses, alterations in phytohormone homeostasis, and networking by defense signaling components are all potential mechanisms involved in Si-triggered resistance responses. This review summarizes the roles of Si in plant–microbe interactions, evaluates the potential for improving plant resistance by modifying Si fertilizer inputs, and highlights future research concerning the role of Si in agriculture. PMID:28529517

  13. A Core Regulatory Pathway Controlling Rice Tiller Angle Mediated by the LAZY1-dependent Asymmetric Distribution of Auxin.

    PubMed

    Zhang, Ning; Yu, Hong; Yu, Hao; Cai, Yueyue; Huang, Linzhou; Xu, Cao; Xiong, Guosheng; Meng, Xiangbing; Wang, Jiyao; Chen, Haofeng; Liu, Guifu; Jing, Yanhui; Yuan, Yundong; Liang, Yan; Li, Shujia; Smith, Steven M; Li, Jiayang; Wang, Yonghong

    2018-06-18

    Tiller angle in cereals is a key shoot architecture trait that strongly influences grain yield. Studies in rice (Oryza sativa L.) have implicated shoot gravitropism in the regulation of tiller angle. However, the functional link between shoot gravitropism and tiller angle is unknown. Here, we conducted a large-scale transcriptome analysis of rice shoots in response to gravistimulation and identified two new nodes of a shoot gravitropism regulatory gene network that also controls rice tiller angle. We demonstrate that HEAT STRESS TRANSCRIPTION FACTOR 2D (HSFA2D) is an upstream positive regulator of the LAZY1-mediated asymmetric auxin distribution pathway. We also show that two functionally redundant transcription factor genes, WUSCHEL RELATED HOMEOBOX6 (WOX6) and WOX11, are expressed asymmetrically in response to auxin to connect gravitropism responses with the control of rice tiller angle. These findings define upstream and downstream genetic components that link shoot gravitropism, asymmetric auxin distribution, and rice tiller angle. The results highlight the power of the high-temporal-resolution RNA-seq dataset, and its use to explore further genetic components controlling tiller angle. Collectively these approaches will identify genes to improve grain yields by facilitating the optimization of plant architecture. © 2018 American Society of Plant Biologists. All rights reserved.

  14. Chromatin regulators as a guide for cancer treatment choice

    PubMed Central

    Gurard-Levin, Zachary A.; Wilson, Laurence O.W.; Pancaldi, Vera; Postel-Vinay, Sophie; Sousa, Fabricio G.; Reyes, Cecile; Marangoni, Elisabetta; Gentien, David; Valencia, Alfonso; Pommier, Yves; Cottu, Paul; Almouzni, Geneviève

    2016-01-01

    The limited capacity to predict a patient’s response to distinct chemotherapeutic agents is a major hurdle in cancer management. The efficiency of a large fraction of current cancer therapeutics (radio- and chemotherapies) is influenced by chromatin structure. Reciprocally, alterations in chromatin organization may impact resistance mechanisms. Here, we explore how the mis-expression of chromatin regulators—factors involved in the establishment and maintenance of functional chromatin domains—can inform about the extent of docetaxel response. We exploit gene Affymetrix and NanoString gene expression data for a set of chromatin regulators generated from breast cancer patient-derived xenograft (PDX) models and patient samples treated with docetaxel. Random Forest classification reveals specific panels of chromatin regulators, including key components of the SWI/SNF chromatin remodeler, which readily distinguish docetaxel high-responders and poor-responders. Further exploration of SWI/SNF components in the comprehensive NCI-60 dataset reveals that the expression inversely correlates with docetaxel sensitivity. Finally, we show that loss of the SWI/SNF subunit BRG1 (SMARCA4) in a model cell line leads to enhanced docetaxel sensitivity. Altogether, our findings point towards chromatin regulators as biomarkers for drug response as well as therapeutic targets to sensitize patients towards docetaxel and combat drug resistance. PMID:27196757

  15. Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells.

    PubMed

    Ma, Jiao; Lu, Pin; Guo, Ailin; Cheng, Shuhua; Zong, Hongliang; Martin, Peter; Coleman, Morton; Wang, Y Lynn

    2014-09-01

    Ibrutinib inhibits Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways. A multicentre phase 2 trial of ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) demonstrated a remarkable response rate. However, approximately one-third of patients have primary resistance to the drug while other patients appear to lose response and develop secondary resistance. Understanding the molecular mechanisms underlying ibrutinib sensitivity is of paramount importance. In this study, we investigated cell lines and primary MCL cells that display differential sensitivity to ibrutinib. We found that the primary cells display a higher BTK activity than normal B cells and MCL cells show differential sensitivity to BTK inhibition. Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib-sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti-tumour activities. Interestingly, inhibition of ERK1/2 and AKT, but not BTK phosphorylation per se, correlates well with cellular response to BTK inhibition in cell lines as well as in primary tumours. Our study suggests that, to prevent primary resistance or to overcome secondary resistance to BTK inhibition, a combinatory strategy that targets multiple components or multiple pathways may represent the most effective approach. © 2014 John Wiley & Sons Ltd.

  16. Heritability of brain activity related to response inhibition: A longitudinal genetic study in adolescent twins.

    PubMed

    Anokhin, Andrey P; Golosheykin, Simon; Grant, Julia D; Heath, Andrew C

    2017-05-01

    The ability to inhibit prepotent but context- or goal-inappropriate responses is essential for adaptive self-regulation of behavior. Deficits in response inhibition, a key component of impulsivity, have been implicated as a core dysfunction in a range of neuropsychiatric disorders such as ADHD and addictions. Identification of genetically transmitted variation in the neural underpinnings of response inhibition can help to elucidate etiological pathways to these disorders and establish the links between genes, brain, and behavior. However, little is known about genetic influences on the neural mechanisms of response inhibition during adolescence, a developmental period characterized by weak self-regulation of behavior. Here we investigated heritability of ERPs elicited in a Go/No-Go task in a large sample of adolescent twins assessed longitudinally at ages 12, 14, and 16. Genetic analyses showed significant heritability of inhibition-related frontal N2 and P3 components at all three ages, with 50 to 60% of inter-individual variability being attributable to genetic factors. These genetic influences included both common genetic factors active at different ages and novel genetic influences emerging during development. Finally, individual differences in the rate of developmental changes from age 12 to age 16 were significantly influenced by genetic factors. In conclusion, the present study provides the first evidence for genetic influences on neural correlates of response inhibition during adolescence and suggests that ERPs elicited in the Go/No-Go task can serve as intermediate neurophysiological phenotypes (endophenotypes) for the study of disinhibition and impulse control disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Heritability of brain activity related to response inhibition: a longitudinal genetic study in adolescent twins

    PubMed Central

    Anokhin, Andrey P.; Golosheykin, Simon; Grant, Julia D.; Heath, Andrew C.

    2017-01-01

    The ability to inhibit prepotent but context- or goal-inappropriate responses is essential for adaptive self-regulation of behavior. Deficits in response inhibition, a key component of impulsivity, have been implicated as a core dysfunction in a range of neuropsychiatric disorders such as ADHD and addictions. Identification of genetically transmitted variation in the neural underpinnings of response inhibition can help to elucidate etiological pathways to these disorders and establish the links between genes, brain, and behavior. However, little is known about genetic influences on the neural mechanisms of response inhibition during adolescence, a developmental period characterized by weak self-regulation of behavior. Here we investigated heritability of ERPs elicited in a Go/No-Go task in a large sample of adolescent twins assessed longitudinally at ages 12, 14, and 16. Genetic analyses showed significant heritability of inhibition-related frontal N2 and P3 components at all three ages, with 50 to 60% of inter-individual variability being attributable to genetic factors. These genetic influences included both common genetic factors active at different ages and novel genetic influences emerging during development. Finally, individual differences in the rate of developmental changes from age 12 to age 16 were significantly influenced by genetic factors. In conclusion, the present study provides the first evidence for genetic influences on neural correlates of response inhibition during adolescence and suggests that ERPs elicited in the Go/No-Go task can serve as intermediate neurophysiological phenotypes (endophenotypes) for the study of disinhibition and impulse control disorders. PMID:28300615

  18. Optimal multi-type sensor placement for response and excitation reconstruction

    NASA Astrophysics Data System (ADS)

    Zhang, C. D.; Xu, Y. L.

    2016-01-01

    The need to perform dynamic response reconstruction always arises as the measurement of structural response is often limited to a few locations, especially for a large civil structure. Besides, it is usually very difficult, if not impossible, to measure external excitations under the operation condition of a structure. This study presents an algorithm for optimal placement of multi-type sensors, including strain gauges, displacement transducers and accelerometers, for the best reconstruction of responses of key structural components where there are no sensors installed and the best estimation of external excitations acting on the structure at the same time. The algorithm is developed in the framework of Kalman filter with unknown excitation, in which minimum-variance unbiased estimates of the generalized state of the structure and the external excitations are obtained by virtue of limited sensor measurements. The structural responses of key locations without sensors can then be reconstructed with the estimated generalized state and excitation. The asymptotic stability feature of the filter is utilized for optimal sensor placement. The number and spatial location of the multi-type sensors are determined by adding the optimal sensor which gains the maximal reduction of the estimation error of reconstructed responses. For the given mode number in response reconstruction and the given locations of external excitations, the optimal multi-sensor placement achieved by the proposed method is independent of the type and time evolution of external excitation. A simply-supported overhanging steel beam under multiple types of excitation is numerically studied to demonstrate the feasibility and superiority of the proposed method, and the experimental work is then carried out to testify the effectiveness of the proposed method.

  19. Kdo2-lipid A: structural diversity and impact on immunopharmacology

    PubMed Central

    Wang, Xiaoyuan; Quinn, Peter J; Yan, Aixin

    2015-01-01

    3-deoxy-d-manno-octulosonic acid-lipid A (Kdo2-lipid A) is the essential component of lipopolysaccharide in most Gram-negative bacteria and the minimal structural component to sustain bacterial viability. It serves as the active component of lipopolysaccharide to stimulate potent host immune responses through the complex of Toll-like-receptor 4 (TLR4) and myeloid differentiation protein 2. The entire biosynthetic pathway of Escherichia coli Kdo2-lipid A has been elucidated and the nine enzymes of the pathway are shared by most Gram-negative bacteria, indicating conserved Kdo2-lipid A structure across different species. Yet many bacteria can modify the structure of their Kdo2-lipid A which serves as a strategy to modulate bacterial virulence and adapt to different growth environments as well as to avoid recognition by the mammalian innate immune systems. Key enzymes and receptors involved in Kdo2-lipid A biosynthesis, structural modification and its interaction with the TLR4 pathway represent a clear opportunity for immunopharmacological exploitation. These include the development of novel antibiotics targeting key biosynthetic enzymes and utilization of structurally modified Kdo2-lipid A or correspondingly engineered live bacteria as vaccines and adjuvants. Kdo2-lipid A/TLR4 antagonists can also be applied in anti-inflammatory interventions. This review summarizes recent knowledge on both the fundamental processes of Kdo2-lipid A biosynthesis, structural modification and immune stimulation, and applied research on pharmacological exploitations of these processes for therapeutic development. PMID:24838025

  20. HemR is an OmpR/PhoB-like response regulator from Leptospira, which simultaneously effects transcriptional activation and repression of key haem metabolism genes.

    PubMed

    Morero, Natalia R; Botti, Horacio; Nitta, Kazuhiro R; Carrión, Federico; Obal, Gonzalo; Picardeau, Mathieu; Buschiazzo, Alejandro

    2014-10-01

    Several Leptospira species cause leptospirosis, the most extended zoonosis worldwide. In bacteria, two-component systems constitute key signalling pathways, some of which are involved in pathogenesis. The physiological roles of two-component systems in Leptospira are largely unknown, despite identifying several dozens within their genomes. Biochemical confirmation of an operative phosphorelaying two-component system has been obtained so far only for the Hklep/Rrlep pair. It is known that hklep/rrlep knockout strains of Leptospira biflexa result in haem auxotrophy, although their de novo biosynthesis machinery remains fully functional. Haem is essential for Leptospira, but information about Hklep/Rrlep effector function(s) and target(s) is still lacking. We are now reporting a thorough molecular characterization of this system, which we rename HemK/HemR. The DNA HemR-binding motif was determined, and found within the genomes of saprophyte and pathogenic Leptospira. In this way, putative HemR-regulated genes were pinpointed, including haem catabolism-related (hmuO - haem oxygenase) and biosynthesis-related (the hemA/C/D/B/L/E/N/G operon). Specific HemR binding to these two promoters was quantified, and a dual function was observed in vivo, inversely repressing the hmuO, while activating the hemA operon transcription. The crystal structure of HemR receiver domain was determined, leading to a mechanistic model for its dual regulatory role. © 2014 John Wiley & Sons Ltd.

  1. Components of breeding productivity in a marine bird community: key factors and concordance

    USGS Publications Warehouse

    Hatch, Scott A.; Hatch, Martha A.

    1990-01-01

    We estimated components of annual breeding productivity for eight species of marine birds on the Semidi Islands in the western Gulf of Alaska. Mortality of eggs and young, caused primarily by avian predators, accounted for most of the annual variation in productivity. Failure to produce eggs, clutch size variation, and the hatchability of eggs were generally less important. The stage of breeding at which annual productivity was most strongly regulated differed among species. In murres, chick-rearing success accounted for the largest share of annual variation in overall productivity, whereas incubation success was the key factor in fulmars, kittiwakes, and puffins. Although avian predators were the dominant proximate cause of egg and chick losses in some species, food supply seemed ultimately responsible for variation in all the major components of productivity. Concordance of productivity among species was low for the marine bird community as a whole, but selected pairs of species exhibited a greater tendency for high and low productivities to occur in the same years. Compared with the same or similar species outside Alaska, Semidi Islands birds were in one of three categories: (i) species whose productivity was about the same as reported from other areas (fulmars and gulls), (ii) species with comparatively low productivity (murres, puffins, kittiwakes), and (iii) species with similar mean productivity but greater annual variation (cormorants). These patterns suggest that specialized consumers of forage fish experienced food shortages at the Semidi Islands and that surface feeders were more severely affected than divers.

  2. Mode of action associated with development of hemangiosarcoma in mice given pregabalin and assessment of human relevance.

    PubMed

    Criswell, Kay A; Cook, Jon C; Wojcinski, Zbigniew; Pegg, David; Herman, James; Wesche, David; Giddings, John; Brady, Joseph T; Anderson, Timothy

    2012-07-01

    Pregabalin increased the incidence of hemangiosarcomas in carcinogenicity studies of 2-year mice but was not tumorigenic in rats. Serum bicarbonate increased within 24 h of pregabalin administration in mice and rats. Rats compensated appropriately, but mice developed metabolic alkalosis and increased blood pH. Local tissue hypoxia and increased endothelial cell proliferation were also confirmed in mice alone. The combination of hypoxia and sustained increases in endothelial cell proliferation, angiogenic growth factors, dysregulated erythropoiesis, and macrophage activation is proposed as the key event in the mode of action (MOA) for hemangiosarcoma formation. Hemangiosarcomas occur spontaneously in untreated control mice but occur only rarely in humans. The International Programme on Chemical Safety and International Life Sciences Institute developed a Human Relevance Framework (HRF) analysis whereby presence or absence of key events can be used to assess human relevance. The HRF combines the MOA with an assessment of biologic plausibility in humans to assess human relevance. This manuscript compares the proposed MOA with Hill criteria, a component of the HRF, for strength, consistency, specificity, temporality, and dose response, with an assessment of key biomarkers in humans, species differences in response to disease conditions, and spontaneous incidence of hemangiosarcoma to evaluate human relevance. Lack of key biomarker events in the MOA in rats, monkeys, and humans supports a species-specific process and demonstrates that the tumor findings in mice are not relevant to humans at the clinical dose of pregabalin. Based on this collective dataset, clinical use of pregabalin would not pose an increased risk for hemangiosarcoma to humans.

  3. An Exploratory Qualitative Inquiry of Key Indicators on IT Disaster Recovery Planning

    ERIC Educational Resources Information Center

    Gardner, Brian

    2016-01-01

    Disaster recovery planning is a crucial component to maintaining a business's economic stability. However, it is unclear how key performance indicators (KPIs) are perceived in the emergency medical service (EMS) industry during the disaster recover planning process. The problem addressed in this study was to understand KPIs and their components.…

  4. Assuring Quality in Online Course Delivery

    ERIC Educational Resources Information Center

    Matuga, Julia M.; Wooldridge, Deborah G.; Poirier, Sandra

    2011-01-01

    This paper examines the critical issue of assuring quality online course delivery by examining four key components of online teaching and learning. The topic of course delivery is viewed as a cultural issue that permeates processes from the design of an online course to its evaluation. First, the authors examine and review key components of and…

  5. Intracellular self-assembly based multi-labeling of key viral components: Envelope, capsid and nucleic acids.

    PubMed

    Wen, Li; Lin, Yi; Zhang, Zhi-Ling; Lu, Wen; Lv, Cheng; Chen, Zhi-Liang; Wang, Han-Zhong; Pang, Dai-Wen

    2016-08-01

    Envelope, capsid and nucleic acids are key viral components that are all involved in crucial events during virus infection. Thus simultaneous labeling of these key components is an indispensable prerequisite for monitoring comprehensive virus infection process and dissecting virus infection mechanism. Baculovirus was genetically tagged with biotin on its envelope protein GP64 and enhanced green fluorescent protein (EGFP) on its capsid protein VP39. Spodoptera frugiperda 9 (Sf9) cells were infected by the recombinant baculovirus and subsequently fed with streptavidin-conjugated quantum dots (SA-QDs) and cell-permeable nucleic acids dye SYTO 82. Just by genetic engineering and virus propagation, multi-labeling of envelope, capsid and nucleic acids was spontaneously accomplished during virus inherent self-assembly process, significantly simplifying the labeling process while maintaining virus infectivity. Intracellular dissociation and transportation of all the key viral components, which was barely reported previously, was real-time monitored based on the multi-labeling approach, offering opportunities for deeply understanding virus infection and developing anti-virus treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Smart Buildings and Demand Response

    NASA Astrophysics Data System (ADS)

    Kiliccote, Sila; Piette, Mary Ann; Ghatikar, Girish

    2011-11-01

    Advances in communications and control technology, the strengthening of the Internet, and the growing appreciation of the urgency to reduce demand side energy use are motivating the development of improvements in both energy efficiency and demand response (DR) systems in buildings. This paper provides a framework linking continuous energy management and continuous communications for automated demand response (Auto-DR) in various times scales. We provide a set of concepts for monitoring and controls linked to standards and procedures such as Open Automation Demand Response Communication Standards (OpenADR). Basic building energy science and control issues in this approach begin with key building components, systems, end-uses and whole building energy performance metrics. The paper presents a framework about when energy is used, levels of services by energy using systems, granularity of control, and speed of telemetry. DR, when defined as a discrete event, requires a different set of building service levels than daily operations. We provide examples of lessons from DR case studies and links to energy efficiency.

  7. Genome-wide analysis of alternative splicing during dendritic cell response to a bacterial challenge.

    PubMed

    Rodrigues, Raquel; Grosso, Ana Rita; Moita, Luís

    2013-01-01

    The immune system relies on the plasticity of its components to produce appropriate responses to frequent environmental challenges. Dendritic cells (DCs) are critical initiators of innate immunity and orchestrate the later and more specific adaptive immunity. The generation of diversity in transcriptional programs is central for effective immune responses. Alternative splicing is widely considered a key generator of transcriptional and proteomic complexity, but its role has been rarely addressed systematically in immune cells. Here we used splicing-sensitive arrays to assess genome-wide gene- and exon-level expression profiles in human DCs in response to a bacterial challenge. We find widespread alternative splicing events and splicing factor transcriptional signatures induced by an E. coli challenge to human DCs. Alternative splicing acts in concert with transcriptional modulation, but these two mechanisms of gene regulation affect primarily distinct functional gene groups. Alternative splicing is likely to have an important role in DC immunobiology because it affects genes known to be involved in DC development, endocytosis, antigen presentation and cell cycle arrest.

  8. Statistical Physics of T-Cell Development and Pathogen Specificity

    NASA Astrophysics Data System (ADS)

    Košmrlj, Andrej; Kardar, Mehran; Chakraborty, Arup K.

    2013-04-01

    In addition to an innate immune system that battles pathogens in a nonspecific fashion, higher organisms, such as humans, possess an adaptive immune system to combat diverse (and evolving) microbial pathogens. Remarkably, the adaptive immune system mounts pathogen-specific responses, which can be recalled upon reinfection with the same pathogen. It is difficult to see how the adaptive immune system can be preprogrammed to respond specifically to a vast and unknown set of pathogens. Although major advances have been made in understanding pertinent molecular and cellular phenomena, the precise principles that govern many aspects of an immune response are largely unknown. We discuss complementary approaches from statistical mechanics and cell biology that can shed light on how key components of the adaptive immune system, T cells, develop to enable pathogen-specific responses against many diverse pathogens. The mechanistic understanding that emerges has implications for how host genetics may influence the development of T cells with differing responses to the human immunodeficiency virus (HIV) infection.

  9. 49 CFR 1.13 - OST Key Responsibilities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false OST Key Responsibilities. 1.13 Section 1.13... of the Secretary § 1.13 OST Key Responsibilities. (a) The OST is responsible for: (1) Providing... Government; (5) Encouraging maximum private development of transportation services; (6) Providing responsive...

  10. 49 CFR 1.13 - OST Key Responsibilities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false OST Key Responsibilities. 1.13 Section 1.13... of the Secretary § 1.13 OST Key Responsibilities. (a) The OST is responsible for: (1) Providing... Government; (5) Encouraging maximum private development of transportation services; (6) Providing responsive...

  11. 49 CFR 1.13 - OST Key Responsibilities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false OST Key Responsibilities. 1.13 Section 1.13... of the Secretary § 1.13 OST Key Responsibilities. (a) The OST is responsible for: (1) Providing... Government; (5) Encouraging maximum private development of transportation services; (6) Providing responsive...

  12. Booming far: the long-range vocal strategy of a lekking bird.

    PubMed

    Cornec, C; Hingrat, Y; Aubin, T; Rybak, F

    2017-08-01

    The pressures of selection acting on transmission of information by acoustic signals are particularly high in long-distance communication networks. Males of the North African houbara bustard ( Chlamydotis undulata undulata ) produce extremely low-frequency vocalizations called 'booms' as a component of their courtship displays. These displays are performed on sites separated by a distance of on average 550 m, constituting exploded leks. Here, we investigate the acoustic features of booms involved in species-specific identity. We first assessed the modifications of acoustic parameters during boom transmission at long range within the natural habitat of the species, finding that the frequency content of booms was reliably transmitted up to 600 m. Additionally, by testing males' behavioural responses to playbacks of modified signals, we found that the presence of the second harmonic and the frequency modulation are the key parameters for species identification, and also that a sequence of booms elicited stronger responses than a single boom. Thus, the coding-decoding process relies on redundant and propagation-resistant features, making the booms particularly well adapted for the long-range transmission of information between males. Moreover, by experimentally disentangling the presentation of visual and acoustic signals, we showed that during the booming phase of courtship, the two sensory modalities act in synergy. The acoustic component is dominant in the context of intra-sexual competition. While the visual component is not necessary to induce agonistic response, it acts as an amplifier and reduces the time of detection of the signaller. The utilization of these adaptive strategies allows houbara males to maximize the active space of vocalizations emitted in exploded leks.

  13. Design of ultraviolet wavelength and standard solution concentrations in relative response factors for simultaneous determination of multi-components with single reference standard in herbal medicines.

    PubMed

    Yang, Ting-Wen; Zhao, Chao; Fan, Yong; Qi, Lian-Wen; Li, Ping

    2015-10-10

    Single standard to determine multi-components (SSDMC) is a practical pattern for quality evaluation of herbal medicines (HMs). However, it remains challenging because of potential inconsistency of relative response factors (RRF) on different instruments. In this work, the effects of two key roles, i.e., ultraviolet (UV) wavelength and standard solution concentrations, on reproducibility of RRF were investigated. The effect of UV wavelength on reproducibility of RRF was studied by plotting the relationship of the peak area ratios (internal standard vs analyte) to wavelengths. The preferable wavelength should be set at the flat parts of the curve. Optimized 300 nm produced a 0.38% RSD for emodin/emodin-8-O-β-D-glucopyranoside on five instruments, much lower than 2.80% obtained from the maximum wavelength at 290 nm. Next, the effects of standard solution concentrations of emodin on its response factor (RF) were investigated. For one single point method, low concentration less than 49 b/k resulted in significant variations in RF. For emodin, when the concentration is higher than 7.00 μg mL(-1), a low standard deviation (SD) value at 0.13 was obtained, while lower than 7.00 μg mL(-1), a high SD at 3.71 was obtained. The developed SSDMC method was then applied to determination of target components in 10 Polygonum cuspidatum samples and showed comparable accuracy to conventional calibration methods with deviation less than 1%. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Proteomic Differences between Male and Female Anterior Cruciate Ligament and Patellar Tendon

    PubMed Central

    Little, Dianne; Thompson, J. Will; Dubois, Laura G.; Ruch, David S.; Moseley, M. Arthur; Guilak, Farshid

    2014-01-01

    The risk of anterior cruciate ligament (ACL) injury and re-injury is greater for women than men. Among other factors, compositional differences may play a role in this differential risk. Patellar tendon (PT) autografts are commonly used during reconstruction. The aim of the study was to compare protein expression in male and female ACL and PT. We hypothesized that there would be differences in key structural components between PT and ACL, and that components of the proteome critical for response to mechanical loading and response to injury would demonstrate significant differences between male and female. Two-dimensional liquid chromatography-tandem mass spectrometry and a label-free quantitative approach was used to identify proteomic differences between male and female PT and ACL. ACL contained less type I and more type III collagen than PT. There were tissue-specific differences in expression of proteoglycans, and ACL was enriched in elastin, tenascin C and X, cartilage oligomeric matrix protein, thrombospondin 4 and periostin. Between male and female donors, alcohol dehydrogenase 1B and complement component 9 were enriched in female compared to male. Myocilin was the major protein enriched in males compared to females. Important compositional differences between PT and ACL were identified, and we identified differences in pathways related to extracellular matrix regulation, complement, apoptosis, metabolism of advanced glycation end-products and response to mechanical loading between males and females. Identification of proteomic differences between male and female PT and ACL has identified novel pathways which may lead to improved understanding of differential ACL injury and re-injury risk between males and females. PMID:24818782

  15. Elasticity of crystalline molecular explosives

    DOE PAGES

    Hooks, Daniel E.; Ramos, Kyle J.; Bolme, C. A.; ...

    2015-04-14

    Crystalline molecular explosives are key components of engineered explosive formulations. In precision applications a high degree of consistency and predictability is desired under a range of conditions to a variety of stimuli. Prediction of behaviors from mechanical response and failure to detonation initiation and detonation performance of the material is linked to accurate knowledge of the material structure and first stage of deformation: elasticity. The elastic response of pentaerythritol tetranitrate (PETN), cyclotrimethylene trinitramine (RDX), and cyclotetramethylene tetranitramine (HMX), including aspects of material and measurement variability, and computational methods are described in detail. Experimental determinations of elastic tensors are compared, andmore » an evaluation of sources of error is presented. Furthermore, computed elastic constants are also compared for these materials and for triaminotrinitrobenzene (TATB), for which there are no measurements.« less

  16. Macrophages Exhibit a Large Repertoire of Activation States via Multiple Mechanisms of Macrophage-activating Factors.

    PubMed

    Sumiya, Y U; Inoue, Takahiro; Ishikawa, Mami; Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Uto, Yoshihiro; Nishikata, Takahito

    2016-07-01

    Macrophages are important components of human defense systems and consequently key to antitumor immunity. Human-serum macrophage activation factor (serum MAF) can activate macrophages, making it a promising reagent for anticancer therapy. We established four different macrophage subtypes through introduction of different culture conditions to THP-1- and U937-derived macrophages. We assessed phagocytic activity to understand subtype responses to typical macrophage activation factors (MAFs) and the activation mechanisms of serum MAF. All four macrophage subtypes differed in their response to all MAFs. Moreover, serum MAF had two different activation mechanisms: N-acetylgalactosamine (GalNAc)-dependent and GalNAc-independent. Macrophage activation states and mechanisms are heterogeneous. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. NEDDylation promotes stress granule assembly.

    PubMed

    Jayabalan, Aravinth Kumar; Sanchez, Anthony; Park, Ra Young; Yoon, Sang Pil; Kang, Gum-Yong; Baek, Je-Hyun; Anderson, Paul; Kee, Younghoon; Ohn, Takbum

    2016-07-06

    Stress granules (SGs) harbour translationally stalled messenger ribonucleoproteins and play important roles in regulating gene expression and cell fate. Here we show that neddylation promotes SG assembly in response to arsenite-induced oxidative stress. Inhibition or depletion of key components of the neddylation machinery concomitantly inhibits stress-induced polysome disassembly and SG assembly. Affinity purification and subsequent mass-spectrometric analysis of Nedd8-conjugated proteins from translationally stalled ribosomal fractions identified ribosomal proteins, translation factors and RNA-binding proteins (RBPs), including SRSF3, a previously known SG regulator. We show that SRSF3 is selectively neddylated at Lys85 in response to arsenite. A non-neddylatable SRSF3 (K85R) mutant do not prevent arsenite-induced polysome disassembly, but fails to support the SG assembly, suggesting that the neddylation pathway plays an important role in SG assembly.

  18. Infrared studies of topological insulator systems

    NASA Astrophysics Data System (ADS)

    Post, Kirk; Chapler, Brian; Schafgans, Alex; Liu, Mengkun; Wu, Jih-Sheng; Richardella, Anthony; Lee, Joon Sue; Reijnders, Anjan; Lee, Yun Sang; He, Liang; Kou, Xufeng; Novak, Mario; Taskin, Alexey; Segawa, Kouji; Goldflam, Michael; Stinson, H. Theodore; Qi, Xiao Liang; Burch, Kenneth; Wang, Kang; Fogler, Michael; Samarth, Nitin; Ando, Yoichi; Basov, Dimitri

    The theoretical prediction, and subsequent experimental realization, of topological insulator (TI) systems, has vaulted this new class of materials to the vanguard of condensed matter physics. Since their discovery, we have carried out a number of infrared studies on various TI systems, including Bi2Se3, Bi1-xSbx, and Bi2-xSbxTe3-ySey crystals as well as Bi2Se3 and (Bi,Sb)2Te3 thin films. A key element of these works is the revelation that the infrared response of Bi1-xSbx crystals and (Bi,Sb)2Te3 thin films possess a significant, or even dominant, component from the topologically protected surface states. I will review these works and discuss future prospects of measuring the surface state response through optical spectroscopy techniques

  19. HSP70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene.

    PubMed

    He, H; Chen, C; Xie, Y; Asea, A; Calderwood, S K

    2000-11-01

    Heat shock protein 70 (HSP70) is a molecular chaperone involved in protein folding and resistance to the deleterious effects of stress. Here we show that HSP70 suppresses transcription of c-fos, an early response gene that is a key component of the ubiquitous AP-1 transcription factor complex. HSP70 repressed Ras-induced c-fos transcription only in the presence of functional heat shock factor1 (HSF1). This suggests that HSP70 functions as a corepressor with HSF1 to inhibit c-fos gene transcription. Therefore, besides its known function in the stress response, HSP70 also has the property of a corepressor and combines with HSF1 to antagonize Fos expression and may thus impact multiple aspects of cell regulation.

  20. Biologically Inspired Model for Visual Cognition Achieving Unsupervised Episodic and Semantic Feature Learning.

    PubMed

    Qiao, Hong; Li, Yinlin; Li, Fengfu; Xi, Xuanyang; Wu, Wei

    2016-10-01

    Recently, many biologically inspired visual computational models have been proposed. The design of these models follows the related biological mechanisms and structures, and these models provide new solutions for visual recognition tasks. In this paper, based on the recent biological evidence, we propose a framework to mimic the active and dynamic learning and recognition process of the primate visual cortex. From principle point of view, the main contributions are that the framework can achieve unsupervised learning of episodic features (including key components and their spatial relations) and semantic features (semantic descriptions of the key components), which support higher level cognition of an object. From performance point of view, the advantages of the framework are as follows: 1) learning episodic features without supervision-for a class of objects without a prior knowledge, the key components, their spatial relations and cover regions can be learned automatically through a deep neural network (DNN); 2) learning semantic features based on episodic features-within the cover regions of the key components, the semantic geometrical values of these components can be computed based on contour detection; 3) forming the general knowledge of a class of objects-the general knowledge of a class of objects can be formed, mainly including the key components, their spatial relations and average semantic values, which is a concise description of the class; and 4) achieving higher level cognition and dynamic updating-for a test image, the model can achieve classification and subclass semantic descriptions. And the test samples with high confidence are selected to dynamically update the whole model. Experiments are conducted on face images, and a good performance is achieved in each layer of the DNN and the semantic description learning process. Furthermore, the model can be generalized to recognition tasks of other objects with learning ability.

  1. Caspase-8 modulates Dectin-1 and CR3 driven IL-1β production in response to β-glucans and the fungal pathogen, Candida albicans1

    PubMed Central

    Ganesan, Sandhya; Rathinam, Vijay A. K.; Bossaller, Lukas; Army, Kelly; Kaiser, William J.; Mocarski, Edward S.; Dillon, Christopher P.; Green, Douglas R.; Mayadas, Tanya N.; Levitz, Stuart M.; Hise, Amy G.

    2014-01-01

    Inflammasomes are central mediators of host defense to a wide range of microbial pathogens. The NLRP3 inflammasome plays a key role in triggering caspase-1 dependent IL-1β maturation and resistance to fungal dissemination in Candida albicans infection. β-glucans are major components of fungal cell walls that trigger IL-1β secretion in both murine and human immune cells. In this study, we sought to determine the contribution of β-glucans to C. albicans-induced inflammasome responses in mouse dendritic cells. We show that the NLRP3-ASC-caspase-1 inflammasome is absolutely critical for IL-1β production in response to β-glucans. Interestingly, we also found that both Complement Receptor 3 (CR3/Mac-1) and dectin-1 play a crucial role in coordinating β-glucan-induced IL-1β processing as well as a cell death response. In addition to the essential role of caspase-1, we identify an important role for the pro-apoptotic protease caspase-8 in promoting β-glucan-induced cell death and NLRP3 inflammasome-dependent IL-1β maturation. A strong requirement for Complement Receptor 3 and caspase-8 was also found for NLRP3 dependent IL-1β production in response to heat killed Candida albicans. Together, these results define the importance of dectin-1, CR3 and caspase-8, in addition to the canonical NLRP3 inflammasome, in mediating β-glucan and C. albicans induced innate responses in dendritic cells. Collectively, these findings establish a novel link between β-glucan recognition receptors and the inflammatory proteases caspase-8 and caspase-1 in coordinating cytokine secretion and cell death in response to immunostimulatory fungal components. PMID:25063877

  2. 78 FR 3081 - Petition for Exemption From the Federal Motor Vehicle Motor Theft Prevention Standard; Toyota

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-15

    ... receiver, electrical key and an electronic control module (ECM). The conventional key components consist of a transponder key ECU assembly, transponder key coil, security indicator, ignition key and an ECM... certification ECU and steering lock ECU receive confirmation of the valid key, allowing the ECM to start the...

  3. National Incident Management System (NIMS) Standards Review Panel Workshop Summary Report

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

    Stenner, Robert D.; Kirk, Jennifer L.; Stanton, James R.

    The importance and need for full compliant implementation of NIMS nationwide was clearly demonstrated during the Hurricane Katrina event, which was clearly expressed in Secretary Chertoff's October 4, 2005 letter addressed to the State's governors. It states, ''Hurricane Katrina was a stark reminder of how critical it is for our nation to approach incident management in a coordinated, consistent, and efficient manner. We must be able to come together, at all levels of government, to prevent, prepare for, respond to, and recover from any emergency or disaster. Our operations must be seamless and based on common incident management doctrine, becausemore » the challenges we face as a nation are far greater than capabilities of any one jurisdiction.'' The NIMS is a system/architecture for organizing response on a ''national'' level. It incorporations ICS as a main component of that structure (i.e., it institutionalizes ICS in NIMS). In a paper published on the NIMS Website, the following statements were made: ''NIMS represents a core set of doctrine, principles, terminology, and organizational processes to enable effective, efficient and collaborative incident management at all levels. To provide the framework for interoperability and compatibility, the NIMS is based on a balance between flexibility and standardization.'' Thus the NIC is challenged with the need to adopt quality SDO generated standards to support NIMS compliance, but in doing so maintain the flexibility necessary so that response operations can be tailored for the specific jurisdictional and geographical needs across the nation. In support of this large and complex challenge facing the NIC, the Pacific Northwest National Laboratory (PNNL) was asked to provide technical support to the NIC, through their DHS Science and Technology ? Standards Portfolio Contract, to help identify, review, and develop key standards for NIMS compliance. Upon examining the challenge, the following general process appears to be a reasonable approach for identifying and establishing existing standards that would be applicable to NIMS compliance. The suggested generalized steps to establishing existing SDO generated standards for NIMS compliance are: (1) establish search criteria from the NIMS and its support documents, (2) search SDO databases to identify key existing nationally and/or internationally recognized standards that have potential application to NIMS compliance needs, (3) review the identified standards against the specific component needs of the NIMS, (4) identify the pertinent aspects/components of those identified standards that clearly address specific NIMS compliance needs, (5) establish a process to adopt the pertinent standards, which includes the generation of formalized FEMA Guidance that identifies the specific NIMS component compliance needs addressed in the respective standard, (6) develop performance criteria for which to measure compliance with the identified NIMS components addressed by the respective adopted standard, and (7) adopt the standard, publish the guidance and performance criteria, and incorporate it into routine FEMA/NIC NIMS management operations. This review process will also help identify real gaps in standards for which new NIMS specific standards should be developed. To jump start this process and hopefully identify some key ''low hanging fruit'' standards the NIC could use to begin such a process, a panel of first-responder experts (familiar with the current standards of common use in the first-responder community) from various response disciplines was formed and a workshop held. The workshop included a pre-workshop information gathering process. This report discusses the workshop and its findings in detail.« less

  4. Tendons – time to revisit inflammation

    PubMed Central

    Rees, Jonathan D; Stride, Matthew; Scott, Alex

    2014-01-01

    It is currently widely accepted among clinicians that chronic tendinopathy is caused by a degenerative process devoid of inflammation. Current treatment strategies are focused on physical treatments, peritendinous or intratendinous injections of blood or blood products and interruption of painful stimuli. Results have been at best, moderately good and at worst a failure. The evidence for non-infammatory degenerative processes alone as the cause of tendinopathy is surprisingly weak. There is convincing evidence that the inflammatory response is a key component of chronic tendinopathy. Newer anti-inflammatory modalities may provide alternative potential opportunities in treating chronic tendinopathies and should be explored further. PMID:23476034

  5. Diversity and specificity: auxin perception and signaling through the TIR1/AFB pathway

    DOE PAGES

    Wang, Renhou; Estelle, Mark

    2014-07-15

    Auxin is a versatile plant hormone that plays an essential role in most aspects of plant growth and development. Auxin regulates various growth processes by modulating gene transcription through a SCF TIR1/AFB-Aux/IAA-ARF nuclear signaling module. Recent work has generated clues as to how multiple layers of regulation of the auxin signaling components may result in diverse and specific response outputs. Finally, in particular, interaction and structural studies of key auxin signaling proteins have produced novel insights into the molecular basis of auxin-regulated transcription and may lead to a refined auxin signaling model.

  6. UV-B photoreceptor-mediated signalling in plants.

    PubMed

    Heijde, Marc; Ulm, Roman

    2012-04-01

    Ultraviolet-B radiation (UV-B) is a key environmental signal that is specifically perceived by plants to promote UV acclimation and survival in sunlight. Whereas the plant photoreceptors for visible light are rather well characterised, the UV-B photoreceptor UVR8 was only recently described at the molecular level. Here, we review the current understanding of the UVR8 photoreceptor-mediated pathway in the context of UV-B perception mechanism, early signalling components and physiological responses. We further outline the commonalities in UV-B and visible light signalling as well as highlight differences between these pathways. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Tyrosine kinases in inflammatory dermatologic disease

    PubMed Central

    Paniagua, Ricardo T.; Fiorentino, David; Chung, Lorinda; Robinson, William H.

    2010-01-01

    Tyrosine kinases are enzymes that catalyze the phosphorylation of tyrosine residues on protein substrates. They are key components of signaling pathways that drive an array of cellular responses including proliferation, differentiation, migration, and survival. Specific tyrosine kinases have recently been identified as critical to the pathogenesis of several autoimmune and inflammatory diseases. Small-molecule inhibitors of tyrosine kinases are emerging as a novel class of therapy that may provide benefit in certain patient subsets. In this review, we highlight tyrosine kinase signaling implicated in inflammatory dermatologic diseases, evaluate strategies aimed at inhibiting these aberrant signaling pathways, and discuss prospects for future drug development. PMID:20584561

  8. The role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases.

    PubMed

    Mack, Ines; Hector, Andreas; Ballbach, Marlene; Kohlhäufl, Julius; Fuchs, Katharina J; Weber, Alexander; Mall, Marcus A; Hartl, Dominik

    2015-12-01

    Chitin, after cellulose, the second most abundant biopolymer on earth, is a key component of insects, fungi, and house-dust mites. Lower life forms are endowed with chitinases to defend themselves against chitin-bearing pathogens. Unexpectedly, humans were also found to express chitinases as well as chitinase-like proteins that modulate immune responses. Particularly, increased levels of the chitinase-like protein YKL-40 have been associated with severe asthma, cystic fibrosis, and other inflammatory disease conditions. Here, we summarize and discuss the potential role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases.

  9. Evaluation of Chemical Coating Processes for AXAF

    NASA Technical Reports Server (NTRS)

    Engelhaupt, Darell E.

    1997-01-01

    The need existed at MSFC for the development and fabrication of radioisotope calibration sources of cadmium 109 and iron 55 isotopes. This was in urgent response to the AXAF program. Several issues persisted in creating manufacturing difficulties for the supplier. In order to meet the MSFC requirements very stringent control needed to be maintained for the coating quality, specific activity and thickness. Due to the difficulties in providing the precisely controlled devices for testing, the delivery of the sources was seriously delayed. It became imperative that these fabrication issues be resolved to avoid further delays in this AXAF observatory key component.

  10. Forensic aspects and assessment of school bullying.

    PubMed

    Freeman, Bradley W; Thompson, Christopher; Jaques, Cory

    2012-12-01

    This article describes school's obligations related to bullying behavior, the assessment of bullying students and their victims, the evaluation of claimed damages due to bullying, and potential interventions for both individuals and school systems to reduce the frequency of bullying behavior. This article assists evaluators when assessing youth who are involved in bullying behavior, either as victims or perpetrators. Key areas highlighted include an overview of bullying behaviors, legal issues related to a school's responsibility in preventing or curtailing bullying behaviors, important components of a bullying assessment, and proposed interventions to minimize bullying. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Extracellular vesicles are key intercellular mediators in the development of immune dysfunction to allergens in the airways.

    PubMed

    Shin, T-S; Kim, J H; Kim, Y-S; Jeon, S G; Zhu, Z; Gho, Yong Song; Kim, Yoon-Keun

    2010-10-01

    Previous evidence indicates that inhalation of lipopolysaccharide (LPS)-containing with allergens induced mixed Th1 and Th17 cell responses in the airways. Extracellular vesicles (EVs) are nanometer-sized spherical, lipid-bilayered structures and are recently in the public eye as an intercellular communicator in immune responses. To evaluate the role of EVs secreted by LPS inhalation in the development of airway immune dysfunction in response to allergens. Extracellular vesicles in bronchoalveolar lavage fluids of BALB/c mice were isolated and characterized 24 h after applications to the airway of 10 μg of LPS for 3 days. To evaluate the role of LPS-induced EVs on the development of airway immune dysfunction, in vivo and in vitro experiments were performed using the isolated LPS-induced EVs. The inhalation of LPS enhanced EVs release into the BAL fluid, when compared to the application of PBS. Airway sensitization with allergens and LPS-induced EVs resulted in a mixed Th1 and Th17 cell responses, although that with allergens and PBS-induced EVs induced immune tolerance. In addition, LPS-induced EVs enhanced the production of Th1- and Th17-polarizing cytokines (IL-12p70 and IL-6, respectively) by lung dendritic cells. Moreover, the immune responses induced by the LPS-induced EVs were blocked by denaturation of the EV-bearing proteins. These data suggest that EVs (especially, the protein components) secreted by LPS inhalation are a key intercellular communicator in the development of airway immune dysfunction to inhaled LPS-containing allergens.

  12. Extracellular vesicles are key intercellular mediators in the development of immune dysfunction to allergens in the airways

    PubMed Central

    Shin, T-S; Kim, J H; Kim, Y-S; Jeon, S G; Zhu, Z; Gho, Y S; Kim, Y-K

    2010-01-01

    Background Previous evidence indicates that inhalation of lipopolysaccharide (LPS)-containing with allergens induced mixed Th1 and Th17 cell responses in the airways. Extracellular vesicles (EVs) are nanometer-sized spherical, lipid-bilayered structures and are recently in the public eye as an intercellular communicator in immune responses. Objective To evaluate the role of EVs secreted by LPS inhalation in the development of airway immune dysfunction in response to allergens. Methods Extracellular vesicles in bronchoalveolar lavage fluids of BALB/c mice were isolated and characterized 24 h after applications to the airway of 10 μg of LPS for 3 days. To evaluate the role of LPS-induced EVs on the development of airway immune dysfunction, in vivo and in vitro experiments were performed using the isolated LPS-induced EVs. Results The inhalation of LPS enhanced EVs release into the BAL fluid, when compared to the application of PBS. Airway sensitization with allergens and LPS-induced EVs resulted in a mixed Th1 and Th17 cell responses, although that with allergens and PBS-induced EVs induced immune tolerance. In addition, LPS-induced EVs enhanced the production of Th1- and Th17-polarizing cytokines (IL-12p70 and IL-6, respectively) by lung dendritic cells. Moreover, the immune responses induced by the LPS-induced EVs were blocked by denaturation of the EV-bearing proteins. Conclusion These data suggest that EVs (especially, the protein components) secreted by LPS inhalation are a key intercellular communicator in the development of airway immune dysfunction to inhaled LPS-containing allergens. PMID:20337607

  13. Evaluating in Vitro Culture Medium of Gut Microbiome with Orthogonal Experimental Design and a Metaproteomics Approach.

    PubMed

    Li, Leyuan; Zhang, Xu; Ning, Zhibin; Mayne, Janice; Moore, Jasmine I; Butcher, James; Chiang, Cheng-Kang; Mack, David; Stintzi, Alain; Figeys, Daniel

    2018-01-05

    In vitro culture based approaches are time- and cost-effective solutions for rapidly evaluating the effects of drugs or natural compounds against microbiomes. The nutritional composition of the culture medium is an important determinant for effectively maintaining the gut microbiome in vitro. This study combines orthogonal experimental design and a metaproteomics approach to obtaining functional insights into the effects of different medium components on the microbiome. Our results show that the metaproteomic profile respond differently to medium components, including inorganic salts, bile salts, mucin, and short-chain fatty acids. Multifactor analysis of variance further revealed significant main and interaction effects of inorganic salts, bile salts, and mucin on the different functional groups of gut microbial proteins. While a broad regulating effect was observed on basic metabolic pathways, different medium components also showed significant modulations on cell wall, membrane, and envelope biogenesis and cell motility related functions. In particular, flagellar assembly related proteins were significantly responsive to the presence of mucin. This study provides information on the functional influences of medium components on the in vitro growth of microbiome communities and gives insight on the key components that must be considered when selecting and optimizing media for culturing ex vivo microbiotas.

  14. B Cell-Intrinsic IDO1 Regulates Humoral Immunity to T Cell-Independent Antigens.

    PubMed

    Shinde, Rahul; Shimoda, Michiko; Chaudhary, Kapil; Liu, Haiyun; Mohamed, Eslam; Bradley, Jillian; Kandala, Sridhar; Li, Xia; Liu, Kebin; McGaha, Tracy L

    2015-09-01

    Humoral responses to nonproteinaceous Ags (i.e., T cell independent [TI]) are a key component of the early response to bacterial and viral infection and a critical driver of systemic autoimmunity. However, mechanisms that regulate TI humoral immunity are poorly defined. In this study, we report that B cell-intrinsic induction of the tryptophan-catabolizing enzyme IDO1 is a key mechanism limiting TI Ab responses. When Ido1(-/-) mice were immunized with TI Ags, there was a significant increase in Ab titers and formation of extrafollicular Ab-secreting cells compared with controls. This effect was specific to TI Ags, as Ido1 disruption did not affect Ig production after immunization with protein Ags. The effect of IDO1 abrogation was confined to the B cell compartment, as adoptive transfer of Ido1(-/-) B cells to B cell-deficient mice was sufficient to replicate increased TI responses observed in Ido1(-/-) mice. Moreover, in vitro activation with TLR ligands or BCR crosslinking rapidly induced Ido1 expression and activity in purified B cells, and Ido1(-/-) B cells displayed enhanced proliferation and cell survival associated with increased Ig and cytokine production compared with wild-type B cells. Thus, our results demonstrate a novel, B cell-intrinsic, role for IDO1 as a regulator of humoral immunity that has implications for both vaccine design and prevention of autoimmunity. Copyright © 2015 by The American Association of Immunologists, Inc.

  15. Serology in the 21st Century: The Molecular-Level Analysis of the Serum Antibody Repertoire

    PubMed Central

    Wine, Yariv; Horton, Andrew P.; Ippolito, Gregory C.; Georgiou, George

    2015-01-01

    The ensemble of antibodies found in serum and secretions represents the key adaptive component of B-cell mediated humoral immunity. The antibody repertoire is shaped by the historical record of exposure to exogenous factors such as pathogens and vaccines, as well as by endogenous host-intrinsic factors such as genetics, self-antigens, and age. Thanks to very recent technology advancements it is now becoming possible to identify and quantify the individual antibodies comprising the serological repertoire. In parallel, the advent of high throughput methods for antigen and immunosignature discovery opens up unprecedented opportunities to transform our understanding of numerous key questions in adaptive humoral immunity, including the nature and dynamics of serological memory, the role of polyspecific antibodies in health and disease and how protective responses to infections or vaccine challenge arise. Additionally, these technologies also hold great promise for therapeutic antibody and biomarker discovery in a variety of settings PMID:26172290

  16. Processing of hierarchical syntactic structure in music.

    PubMed

    Koelsch, Stefan; Rohrmeier, Martin; Torrecuso, Renzo; Jentschke, Sebastian

    2013-09-17

    Hierarchical structure with nested nonlocal dependencies is a key feature of human language and can be identified theoretically in most pieces of tonal music. However, previous studies have argued against the perception of such structures in music. Here, we show processing of nonlocal dependencies in music. We presented chorales by J. S. Bach and modified versions in which the hierarchical structure was rendered irregular whereas the local structure was kept intact. Brain electric responses differed between regular and irregular hierarchical structures, in both musicians and nonmusicians. This finding indicates that, when listening to music, humans apply cognitive processes that are capable of dealing with long-distance dependencies resulting from hierarchically organized syntactic structures. Our results reveal that a brain mechanism fundamental for syntactic processing is engaged during the perception of music, indicating that processing of hierarchical structure with nested nonlocal dependencies is not just a key component of human language, but a multidomain capacity of human cognition.

  17. Barriers to Providing Health Education During Primary Care Visits at Community Health Centers: Clinical Staff Insights.

    PubMed

    Alicea-Planas, Jessica; Pose, Alix; Smith, Linda

    2016-04-01

    The rapid increase of diverse patients living in the US has created a different set of needs in healthcare, with the persistence of health disparities continuing to challenge the current system. Chronic disease management has been discussed as a way to improve health outcomes, with quality patient education being a key component. Using a community based participatory research framework, this study utilized a web-based survey and explored clinical staff perceptions of barriers to providing patient education during primary care visits. With a response rate of nearly 42 %, appointment time allotment seemed to be one of the most critical factors related to the delivery of health education and should be considered key. The importance of team-based care and staff training were also significant. Various suggestions were made in order to improve the delivery of quality patient education at community health centers located in underserved areas.

  18. Around and beyond 53BP1 Nuclear Bodies.

    PubMed

    Fernandez-Vidal, Anne; Vignard, Julien; Mirey, Gladys

    2017-12-05

    Within the nucleus, sub-nuclear domains define territories where specific functions occur. Nuclear bodies (NBs) are dynamic structures that concentrate nuclear factors and that can be observed microscopically. Recently, NBs containing the p53 binding protein 1 (53BP1), a key component of the DNA damage response, were defined. Interestingly, 53BP1 NBs are visualized during G1 phase, in daughter cells, while DNA damage was generated in mother cells and not properly processed. Unlike most NBs involved in transcriptional processes, replication has proven to be key for 53BP1 NBs, with replication stress leading to the formation of these large chromatin domains in daughter cells. In this review, we expose the composition and organization of 53BP1 NBs and focus on recent findings regarding their regulation and dynamics. We then concentrate on the importance of the replication stress, examine the relation of 53BP1 NBs with DNA damage and discuss their dysfunction.

  19. Predictive codes of familiarity and context during the perceptual learning of facial identities

    NASA Astrophysics Data System (ADS)

    Apps, Matthew A. J.; Tsakiris, Manos

    2013-11-01

    Face recognition is a key component of successful social behaviour. However, the computational processes that underpin perceptual learning and recognition as faces transition from unfamiliar to familiar are poorly understood. In predictive coding, learning occurs through prediction errors that update stimulus familiarity, but recognition is a function of both stimulus and contextual familiarity. Here we show that behavioural responses on a two-option face recognition task can be predicted by the level of contextual and facial familiarity in a computational model derived from predictive-coding principles. Using fMRI, we show that activity in the superior temporal sulcus varies with the contextual familiarity in the model, whereas activity in the fusiform face area covaries with the prediction error parameter that updated facial familiarity. Our results characterize the key computations underpinning the perceptual learning of faces, highlighting that the functional properties of face-processing areas conform to the principles of predictive coding.

  20. Histone modification: cause or cog?

    PubMed

    Henikoff, Steven; Shilatifard, Ali

    2011-10-01

    Histone modifications are key components of chromatin packaging but whether they constitute a 'code' has been contested. We believe that the central issue is causality: are histone modifications responsible for differences between chromatin states, or are differences in modifications mostly consequences of dynamic processes, such as transcription and nucleosome remodeling? We find that inferences of causality are often based on correlation and that patterns of some key histone modifications are more easily explained as consequences of nucleosome disruption in the presence of histone modifying enzymes. We suggest that the 35-year-old DNA accessibility paradigm provides a mechanistically sound basis for understanding the role of nucleosomes in gene regulation and epigenetic inheritance. Based on this view, histone modifications and variants contribute to diversification of a chromatin landscape shaped by dynamic processes that are driven primarily by transcription and nucleosome remodeling. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Design concepts and options for the Thermal Infrared Imager (TIRI) as part of ESA's Asteroid Impact Mission.

    NASA Astrophysics Data System (ADS)

    Bowles, Neil; Calcutt, Simon; Licandro, Javier; Reyes, Marcos; Delbo, Marco; Donaldson Hanna, Kerri; Arnold, Jessica; Howe, Chris

    2016-04-01

    ESA's Asteroid Impact Mission (AIM) is being studied as part of the joint ESA/NASA AIDA mission for launch in 2020. AIDA's primary mission is to investigate the effect of a kinetic impactor on the secondary component of the binary asteroid 65803 Didymos in late 2022. AIM will characterise the Didymos system and monitor the response of the binary system to the impact. A multi-spectral, thermal-infrared imaging instrument (TIRI) will be an essential component of AIM's remote sensing payload, as it will provide key information on the nature of the surfaces (e.g. presence or absence of materials, degree of compaction, and rock abundance of the regolith) of both components in the Didymos system. The temperature maps provided by TIRI will be important for navigation and spacecraft health and safety for proximity/lander operations. By measuring the asteroids' diurnal thermal responses (thermal inertia) and their surface compositions via spectral signatures, TIRI will provide information on the origin and evolution of the binary system. In this presentation we will discuss possible instrument design for TIRI, exploring options that include imaging spectroscopy to broadband imaging. By using thermal models and compositional analogues of the Didymos system we will show how the performance of each design option compares to the wider scientific goals of the AIDA/AIM mission.

  2. A risk-based auditing process for pharmaceutical manufacturers.

    PubMed

    Vargo, Susan; Dana, Bob; Rangavajhula, Vijaya; Rönninger, Stephan

    2014-01-01

    The purpose of this article is to share ideas on developing a risk-based model for the scheduling of audits (both internal and external). Audits are a key element of a manufacturer's quality system and provide an independent means of evaluating the manufacturer's or the supplier/vendor's compliance status. Suggestions for risk-based scheduling approaches are discussed in the article. Pharmaceutical manufacturers are required to establish and implement a quality system. The quality system is an organizational structure defining responsibilities, procedures, processes, and resources that the manufacturer has established to ensure quality throughout the manufacturing process. Audits are a component of the manufacturer's quality system and provide a systematic and an independent means of evaluating the manufacturer's overall quality system and compliance status. Audits are performed at defined intervals for a specified duration. The intention of the audit process is to focus on key areas within the quality system and may not cover all relevant areas during each audit. In this article, the authors provide suggestions for risk-based scheduling approaches to aid pharmaceutical manufacturers in identifying the key focus areas for an audit.

  3. Components of a standardised olive leaf dry extract (Ph. Eur.) promote hypothiocyanite production by lactoperoxidase.

    PubMed

    Flemmig, Jörg; Rusch, Dorothea; Czerwińska, Monika Ewa; Rauwald, Hans-Wilhelm; Arnhold, Jürgen

    2014-05-01

    We investigated in vitro the ability of a standardised olive leaf dry extract (Ph. Eur.) (OLE) as well as of its single components to circumvent the hydrogen peroxide-induced inhibition of the hypothiocyanite-producing activity of lactoperoxidase (LPO). The rate of hypothiocyanite (⁻OSCN) formation by LPO was quantified by spectrophotometric detection of the oxidation of 5-thio-2-nitrobenzoic acid (TNB). By using excess hydrogen peroxide, we forced the accumulation of inactive enzymatic intermediates which are unable to promote the two-electronic oxidation of thiocyanate. Both OLE and certain extract components showed a strong LPO-reactivating effect. Thereby an o-hydroxyphenolic moiety emerged to be essential for a good reactivity with the inactive LPO redox states. This basic moiety is found in the main OLE components oleuropein, oleacein, hydroxytyrosol, caffeic acid as well as in different other constituents including the OLE flavone luteolin. As LPO is a key player in the humoral immune response, these results propose a new mode of action regarding the well-known bacteriostatic and anti-inflammatory properties of the leaf extract of Olea europaea L. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Light and redox switchable molecular components for molecular electronics.

    PubMed

    Browne, Wesley R; Feringa, Ben L

    2010-01-01

    The field of molecular and organic electronics has seen rapid progress in recent years, developing from concept and design to actual demonstration devices in which both single molecules and self-assembled monolayers are employed as light-responsive components. Research in this field has seen numerous unexpected challenges that have slowed progress and the initial promise of complex molecular-based computers has not yet been realised. Primarily this has been due to the realisation at an early stage that molecular-based nano-electronics brings with it the interface between the hard (semiconductor) and soft (molecular) worlds and the challenges which accompany working in such an environment. Issues such as addressability, cross-talk, molecular stability and perturbation of molecular properties (e.g., inhibition of photochemistry) have nevertheless driven development in molecular design and synthesis as well as our ability to interface molecular components with bulk metal contacts to a very high level of sophistication. Numerous groups have played key roles in progressing this field not least teams such as those led by Whitesides, Aviram, Ratner, Stoddart and Heath. In this short review we will however focus on the contributions from our own group and those of our collaborators, in employing diarylethene based molecular components.

  5. Autoshaping and automaintenance of a key-press response in squirrel monkeys

    PubMed Central

    Gamzu, Elkan; Schwam, Elias

    1974-01-01

    Following exposure for a minimum of 500 to 600 trials, three of four naive squirrel monkeys eventually pressed a response key, illumination of which always preceded delivery of a food pellet. Three other naive monkeys did not press the key when the pellets were delivered randomly with respect to key illumination. Despite some similarities to autoshaping using pigeons, the data indicate many points of difference when squirrel monkeys are used as subjects. Although key-food pairings were shown to be important in the acquisition of the key-press response, they were ineffective in maintaining the response when either a negative response-reinforcer dependency was introduced, or when there was no scheduled response-reinforcer dependency (fixed trial). Not all demonstrations of autoshaping can be considered to be under the control of those processes that are primarily responsible for the phenomena obtained in pigeons. PMID:16811749

  6. Autoshaping and automaintenance of a key-press response in squirrel monkeys.

    PubMed

    Gamzu, E; Schwam, E

    1974-03-01

    Following exposure for a minimum of 500 to 600 trials, three of four naive squirrel monkeys eventually pressed a response key, illumination of which always preceded delivery of a food pellet. Three other naive monkeys did not press the key when the pellets were delivered randomly with respect to key illumination. Despite some similarities to autoshaping using pigeons, the data indicate many points of difference when squirrel monkeys are used as subjects. Although key-food pairings were shown to be important in the acquisition of the key-press response, they were ineffective in maintaining the response when either a negative response-reinforcer dependency was introduced, or when there was no scheduled response-reinforcer dependency (fixed trial). Not all demonstrations of autoshaping can be considered to be under the control of those processes that are primarily responsible for the phenomena obtained in pigeons.

  7. Process evaluation of the data-driven quality improvement in primary care (DQIP) trial: active and less active ingredients of a multi-component complex intervention to reduce high-risk primary care prescribing.

    PubMed

    Grant, Aileen; Dreischulte, Tobias; Guthrie, Bruce

    2017-01-07

    Two to 4% of emergency hospital admissions are caused by preventable adverse drug events. The estimated costs of such avoidable admissions in England were £530 million in 2015. The data-driven quality improvement in primary care (DQIP) intervention was designed to prompt review of patients vulnerable from currently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and anti-platelets and was found to be effective at reducing this prescribing. A process evaluation was conducted parallel to the trial, and this paper reports the analysis which aimed to explore response to the intervention delivered to clusters in relation to participants' perceptions about which intervention elements were active in changing their practice. Data generation was by in-depth interview with key staff exploring participant's perceptions of the intervention components. Analysis was iterative using the framework technique and drawing on normalisation process theory. All the primary components of the intervention were perceived as active, but at different stages of implementation: financial incentives primarily supported recruitment; education motivated the GPs to initiate implementation; the informatics tool facilitated sustained implementation. Participants perceived the primary components as interdependent. Intervention subcomponents also varied in whether and when they were active. For example, run charts providing feedback of change in prescribing over time were ignored in the informatics tool, but were motivating in some practices in the regular e-mailed newsletter. The high-risk NSAID and anti-platelet prescribing targeted was accepted as important by all interviewees, and this shared understanding was a key wider context underlying intervention effectiveness. This was a novel use of process evaluation data which examined whether and how the individual intervention components were effective from the perspective of the professionals delivering changed care to patients. These findings are important for reproducibility and roll-out of the intervention. ClinicalTrials.gov, NCT01425502 .

  8. Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer

    PubMed Central

    Ulrich, Cornelia M.; Goode, Ellen L.; Brhane, Yonathan; Muir, Kenneth; Chan, Andrew T.; Marchand, Loic Le; Schildkraut, Joellen; Witte, John S.; Eeles, Rosalind; Boffetta, Paolo; Spitz, Margaret R.; Poirier, Julia G.; Rider, David N.; Fridley, Brooke L.; Chen, Zhihua; Haiman, Christopher; Schumacher, Fredrick; Easton, Douglas F.; Landi, Maria Teresa; Brennan, Paul; Houlston, Richard; Christiani, David C.; Field, John K.; Bickeböller, Heike; Risch, Angela; Kote-Jarai, Zsofia; Wiklund, Fredrik; Grönberg, Henrik; Chanock, Stephen; Berndt, Sonja I.; Kraft, Peter; Lindström, Sara; Al Olama, Ali Amin; Song, Honglin; Phelan, Catherine; Wentzensen, Nicholas; Peters, Ulrike; Slattery, Martha L.; Sellers, Thomas A.; Casey, Graham; Gruber, Stephen B.; Hunter, David J.; Amos, Christopher I.; Henderson, Brian

    2015-01-01

    Background: Inflammation has been hypothesized to increase the risk of cancer development as an initiator or promoter, yet no large-scale study of inherited variation across cancer sites has been conducted. Methods: We conducted a cross-cancer genomic analysis for the inflammation pathway based on 48 genome-wide association studies within the National Cancer Institute GAME-ON Network across five common cancer sites, with a total of 64 591 cancer patients and 74 467 control patients. Subset-based meta-analysis was used to account for possible disease heterogeneity, and hierarchical modeling was employed to estimate the effect of the subcomponents within the inflammation pathway. The network was visualized by enrichment map. All statistical tests were two-sided. Results: We identified three pleiotropic loci within the inflammation pathway, including one novel locus in Ch12q24 encoding SH2B3 (rs3184504), which reached GWAS significance with a P value of 1.78 x 10–8, and it showed an association with lung cancer (P = 2.01 x 10–6), colorectal cancer (GECCO P = 6.72x10-6; CORECT P = 3.32x10-5), and breast cancer (P = .009). We also identified five key subpathway components with genetic variants that are relevant for the risk of these five cancer sites: inflammatory response for colorectal cancer (P = .006), inflammation related cell cycle gene for lung cancer (P = 1.35x10-6), and activation of immune response for ovarian cancer (P = .009). In addition, sequence variations in immune system development played a role in breast cancer etiology (P = .001) and innate immune response was involved in the risk of both colorectal (P = .022) and ovarian cancer (P = .003). Conclusions: Genetic variations in inflammation and its related subpathway components are keys to the development of lung, colorectal, ovary, and breast cancer, including SH2B3, which is associated with lung, colorectal, and breast cancer. PMID:26319099

  9. Lactobacillus johnsonii N6.2 diminishes caspase-1 maturation in the gastrointestinal system of diabetes prone rats.

    PubMed

    Teixeira, L D; Kling, D N; Lorca, G L; Gonzalez, C F

    2018-04-25

    The cells of the gastrointestinal (GI) epithelium are the first to contact the microbiota and food components. As a direct consequence of this, these cells are the first line of defence and key players in priming the immune response. One of the first responses against GI insults is the formation of the inflammasome, a multiprotein complex assembled in response to environmental threats. The formation of the inflammasome regulates caspase-1 by cleaving it into its active form. Once activated, caspase-1 can cleave interleukin-1β (IL-1β), which promotes adaptive and humoral immunity. Some strains, like Lactobacillus johnsonii N6.2, are able to modulate the biosynthesis of important host metabolites mediating inflammation. Of these metabolites are the pro-inflammatory kynurenines. L. johnsonii N6.2 is able to downregulate kynurenines biosynthesis via a redox active mechanism negatively affecting indoleamine 2,3-dioxygenase activity. In this study, we evaluated the effects of L. johnsonii N6.2 combined with the natural antioxidant and anti-inflammatory molecule rosmarinic acid (RA). Inflammasome assembly and the kynurenine pathway were evaluated in GI samples of BioBreeding diabetes-prone (BB-DP) rats. In this work, BB-DP rats were fed daily with RA, L. johnsonii N6.2; or both combined. The transcriptional rate and proteins levels of inflammasome and kynurenine pathway components in ileum tissue were evaluated. Elevated levels of pro-caspase-1 were observed in rats fed with L. johnsonii, while RA had no effect on pro-caspase-1 expression. Western blot assays demonstrated that L. johnsonii fed rats showed lower levels of mature caspase-1, when compared to the other treatments. Furthermore, IL-1β maturation followed a similar pattern across the treatments. Differences were also observed between treatments in expression levels of key enzymes in the kynurenine pathway. These findings support the role of L. johnsonii in modulating the assembly of the inflammasome as well as some steps of the pro-inflammatory kynurenine pathway.

  10. Phyletic Distribution and Lineage-Specific Domain Architectures of Archaeal Two-Component Signal Transduction Systems

    PubMed Central

    Makarova, Kira S.; Wolf, Yuri I.

    2017-01-01

    ABSTRACT The two-component signal transduction (TCS) machinery is a key mechanism of sensing environmental changes in the prokaryotic world. TCS systems have been characterized thoroughly in bacteria but to a much lesser extent in archaea. Here, we provide an updated census of more than 2,000 histidine kinases and response regulators encoded in 218 complete archaeal genomes, as well as unfinished genomes available from metagenomic data. We describe the domain architectures of the archaeal TCS components, including several novel output domains, and discuss the evolution of the archaeal TCS machinery. The distribution of TCS systems in archaea is strongly biased, with high levels of abundance in haloarchaea and thaumarchaea but none detected in the sequenced genomes from the phyla Crenarchaeota, Nanoarchaeota, and Korarchaeota. The archaeal sensor histidine kinases are generally similar to their well-studied bacterial counterparts but are often located in the cytoplasm and carry multiple PAS and/or GAF domains. In contrast, archaeal response regulators differ dramatically from the bacterial ones. Most archaeal genomes do not encode any of the major classes of bacterial response regulators, such as the DNA-binding transcriptional regulators of the OmpR/PhoB, NarL/FixJ, NtrC, AgrA/LytR, and ActR/PrrA families and the response regulators with GGDEF and/or EAL output domains. Instead, archaea encode multiple copies of response regulators containing either the stand-alone receiver (REC) domain or combinations of REC with PAS and/or GAF domains. Therefore, the prevailing mechanism of archaeal TCS signaling appears to be via a variety of protein-protein interactions, rather than direct transcriptional regulation. IMPORTANCE Although the Archaea represent a separate domain of life, their signaling systems have been assumed to be closely similar to the bacterial ones. A study of the domain architectures of the archaeal two-component signal transduction (TCS) machinery revealed an overall similarity of archaeal and bacterial sensory modules but substantial differences in the signal output modules. The prevailing mechanism of archaeal TCS signaling appears to involve various protein-protein interactions rather than direct transcription regulation. The complete list of histidine kinases and response regulators encoded in the analyzed archaeal genomes is available online at http://www.ncbi.nlm.nih.gov/Complete_Genomes/TCSarchaea.html. PMID:29263101

  11. Phyletic Distribution and Lineage-Specific Domain Architectures of Archaeal Two-Component Signal Transduction Systems.

    PubMed

    Galperin, Michael Y; Makarova, Kira S; Wolf, Yuri I; Koonin, Eugene V

    2018-04-01

    The two-component signal transduction (TCS) machinery is a key mechanism of sensing environmental changes in the prokaryotic world. TCS systems have been characterized thoroughly in bacteria but to a much lesser extent in archaea. Here, we provide an updated census of more than 2,000 histidine kinases and response regulators encoded in 218 complete archaeal genomes, as well as unfinished genomes available from metagenomic data. We describe the domain architectures of the archaeal TCS components, including several novel output domains, and discuss the evolution of the archaeal TCS machinery. The distribution of TCS systems in archaea is strongly biased, with high levels of abundance in haloarchaea and thaumarchaea but none detected in the sequenced genomes from the phyla Crenarchaeota , Nanoarchaeota , and Korarchaeota The archaeal sensor histidine kinases are generally similar to their well-studied bacterial counterparts but are often located in the cytoplasm and carry multiple PAS and/or GAF domains. In contrast, archaeal response regulators differ dramatically from the bacterial ones. Most archaeal genomes do not encode any of the major classes of bacterial response regulators, such as the DNA-binding transcriptional regulators of the OmpR/PhoB, NarL/FixJ, NtrC, AgrA/LytR, and ActR/PrrA families and the response regulators with GGDEF and/or EAL output domains. Instead, archaea encode multiple copies of response regulators containing either the stand-alone receiver (REC) domain or combinations of REC with PAS and/or GAF domains. Therefore, the prevailing mechanism of archaeal TCS signaling appears to be via a variety of protein-protein interactions, rather than direct transcriptional regulation. IMPORTANCE Although the Archaea represent a separate domain of life, their signaling systems have been assumed to be closely similar to the bacterial ones. A study of the domain architectures of the archaeal two-component signal transduction (TCS) machinery revealed an overall similarity of archaeal and bacterial sensory modules but substantial differences in the signal output modules. The prevailing mechanism of archaeal TCS signaling appears to involve various protein-protein interactions rather than direct transcription regulation. The complete list of histidine kinases and response regulators encoded in the analyzed archaeal genomes is available online at http://www.ncbi.nlm.nih.gov/Complete_Genomes/TCSarchaea.html. Copyright © 2018 Galperin et al.

  12. Speed in Information Processing with a Computer Driven Visual Display in a Real-time Digital Simulation. M.S. Thesis - Virginia Polytechnic Inst.

    NASA Technical Reports Server (NTRS)

    Kyle, R. G.

    1972-01-01

    Information transfer between the operator and computer-generated display systems is an area where the human factors engineer discovers little useful design data relating human performance to system effectiveness. This study utilized a computer-driven, cathode-ray-tube graphic display to quantify human response speed in a sequential information processing task. The performance criteria was response time to sixteen cell elements of a square matrix display. A stimulus signal instruction specified selected cell locations by both row and column identification. An equal probable number code, from one to four, was assigned at random to the sixteen cells of the matrix and correspondingly required one of four, matched keyed-response alternatives. The display format corresponded to a sequence of diagnostic system maintenance events, that enable the operator to verify prime system status, engage backup redundancy for failed subsystem components, and exercise alternate decision-making judgements. The experimental task bypassed the skilled decision-making element and computer processing time, in order to determine a lower bound on the basic response speed for given stimulus/response hardware arrangement.

  13. Nuclear calcium is required for human T cell activation

    PubMed Central

    Samstag, Yvonne

    2016-01-01

    Calcium signals in stimulated T cells are generally considered single entities that merely trigger immune responses, whereas costimulatory events specify the type of reaction. Here we show that the “T cell calcium signal” is a composite signal harboring two distinct components that antagonistically control genomic programs underlying the immune response. Using human T cells from healthy individuals, we establish nuclear calcium as a key signal in human T cell adaptogenomics that drives T cell activation and is required for signaling to cyclic adenosine monophosphate response element–binding protein and the induction of CD25, CD69, interleukin-2, and γ-interferon. In the absence of nuclear calcium signaling, cytosolic calcium activating nuclear factor of activated T cells translocation directed the genomic response toward enhanced expression of genes that negatively modulate T cell activation and are associated with a hyporesponsive state. Thus, nuclear calcium controls the T cell fate decision between a proliferative immune response and tolerance. Modulators of nuclear calcium–driven transcription may be used to develop a new type of pro-tolerance immunosuppressive therapy. PMID:27810914

  14. Integration of Palliative Care in the Context of Rapid Response

    PubMed Central

    Nelson, Judith E.; Mathews, Kusum S.; Weissman, David E.; Brasel, Karen J.; Campbell, Margaret; Curtis, J. Randall; Frontera, Jennifer A.; Gabriel, Michelle; Hays, Ross M.; Mosenthal, Anne C.; Mulkerin, Colleen; Puntillo, Kathleen A.; Ray, Daniel E.; Weiss, Stefanie P.; Bassett, Rick; Boss, Renee D.; Lustbader, Dana R.

    2015-01-01

    Rapid response teams (RRTs) can effectively foster discussions about appropriate goals of care and address other emergent palliative care needs of patients and families facing life-threatening illness on hospital wards. In this article, The Improving Palliative Care in the ICU (IPAL-ICU) Project brings together interdisciplinary expertise and existing data to address the following: special challenges for providing palliative care in the rapid response setting, knowledge and skills needed by RRTs for delivery of high-quality palliative care, and strategies for improving the integration of palliative care with rapid response critical care. We discuss key components of communication with patients, families, and primary clinicians to develop a goal-directed treatment approach during a rapid response event. We also highlight the need for RRT expertise to initiate symptom relief. Strategies including specific clinician training and system initiatives are then recommended for RRT care improvement. We conclude by suggesting that as evaluation of their impact on other outcomes continues, performance by RRTs in meeting palliative care needs of patients and families should also be measured and improved. PMID:25644909

  15. Analyzing neural responses with vector fields.

    PubMed

    Buneo, Christopher A

    2011-04-15

    Analyzing changes in the shape and scale of single cell response fields is a key component of many neurophysiological studies. Typical analyses of shape change involve correlating firing rates between experimental conditions or "cross-correlating" single cell tuning curves by shifting them with respect to one another and correlating the overlapping data. Such shifting results in a loss of data, making interpretation of the resulting correlation coefficients problematic. The problem is particularly acute for two dimensional response fields, which require shifting along two axes. Here, an alternative method for quantifying response field shape and scale based on correlation of vector field representations is introduced. The merits and limitations of the methods are illustrated using both simulated and experimental data. It is shown that vector correlation provides more information on response field changes than scalar correlation without requiring field shifting and concomitant data loss. An extension of this vector field approach is also demonstrated which can be used to identify the manner in which experimental variables are encoded in studies of neural reference frames. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Probabilistic inversion of expert assessments to inform projections about Antarctic ice sheet responses

    PubMed Central

    Wong, Tony E.; Keller, Klaus

    2017-01-01

    The response of the Antarctic ice sheet (AIS) to changing global temperatures is a key component of sea-level projections. Current projections of the AIS contribution to sea-level changes are deeply uncertain. This deep uncertainty stems, in part, from (i) the inability of current models to fully resolve key processes and scales, (ii) the relatively sparse available data, and (iii) divergent expert assessments. One promising approach to characterizing the deep uncertainty stemming from divergent expert assessments is to combine expert assessments, observations, and simple models by coupling probabilistic inversion and Bayesian inversion. Here, we present a proof-of-concept study that uses probabilistic inversion to fuse a simple AIS model and diverse expert assessments. We demonstrate the ability of probabilistic inversion to infer joint prior probability distributions of model parameters that are consistent with expert assessments. We then confront these inferred expert priors with instrumental and paleoclimatic observational data in a Bayesian inversion. These additional constraints yield tighter hindcasts and projections. We use this approach to quantify how the deep uncertainty surrounding expert assessments affects the joint probability distributions of model parameters and future projections. PMID:29287095

  17. Development of Integrated Magnetic and Kinetic Control-oriented Transport Model for q-profile Response Prediction in EAST Discharges

    NASA Astrophysics Data System (ADS)

    Wang, Hexiang; Schuster, Eugenio; Rafiq, Tariq; Kritz, Arnold; Ding, Siye

    2016-10-01

    Extensive research has been conducted to find high-performance operating scenarios characterized by high fusion gain, good confinement, plasma stability and possible steady-state operation. A key plasma property that is related to both the stability and performance of these advanced plasma scenarios is the safety factor profile. A key component of the EAST research program is the exploration of non-inductively driven steady-state plasmas with the recently upgraded heating and current drive capabilities that include lower hybrid current drive and neutral beam injection. Anticipating the need for tight regulation of the safety factor profile in these plasma scenarios, a first-principles-driven (FPD)control-oriented model is proposed to describe the safety factor profile evolution in EAST in response to the different actuators. The TRANSP simulation code is employed to tailor the FPD model to the EAST tokamak geometry and to convert it into a form suitable for control design. The FPD control-oriented model's prediction capabilities are demonstrated by comparing predictions with experimental data from EAST. Supported by the US DOE under DE-SC0010537,DE-FG02-92ER54141 and DE-SC0013977.

  18. The role of emotion in musical improvisation: an analysis of structural features.

    PubMed

    McPherson, Malinda J; Lopez-Gonzalez, Monica; Rankin, Summer K; Limb, Charles J

    2014-01-01

    One of the primary functions of music is to convey emotion, yet how music accomplishes this task remains unclear. For example, simple correlations between mode (major vs. minor) and emotion (happy vs. sad) do not adequately explain the enormous range, subtlety or complexity of musically induced emotions. In this study, we examined the structural features of unconstrained musical improvisations generated by jazz pianists in response to emotional cues. We hypothesized that musicians would not utilize any universal rules to convey emotions, but would instead combine heterogeneous musical elements together in order to depict positive and negative emotions. Our findings demonstrate a lack of simple correspondence between emotions and musical features of spontaneous musical improvisation. While improvisations in response to positive emotional cues were more likely to be in major keys, have faster tempos, faster key press velocities and more staccato notes when compared to negative improvisations, there was a wide distribution for each emotion with components that directly violated these primary associations. The finding that musicians often combine disparate features together in order to convey emotion during improvisation suggests that structural diversity may be an essential feature of the ability of music to express a wide range of emotion.

  19. Instruction in the Responsible Conduct of Research: An Inventory of Programs and Materials within CTSAs

    PubMed Central

    DuBois, James M.; Schilling, Debie A.; Heitman, Elizabeth; Steneck, Nicholas H.; Kon, Alexander A.

    2010-01-01

    Abstract The National Institutes of Health (NIH) require instruction in the responsible conduct of research (RCR) as a component of any Clinical and Translational Science Award (CTSA). The Educational Materials Group of the NIH CTSA Consortium's Clinical Research Ethics Key Function Committee (CRE‐KFC) conducted a survey of the 38 institutions that held CTSA funding as of January 2009 to determine how they satisfy RCR training requirements. An 8‐item questionnaire was sent by email to directors of the Clinical Research Ethics, the Educational and Career Development, and the Regulatory Knowledge cores. We received 78 completed surveys from 38 CTSAs (100%). We found that there is no unified approach to RCR training across CTSAs, many programs lack a coherent plan for RCR instruction, and most CTSAs have not developed unique instructional materials tailored to the needs of clinical and translational scientists. We recommend collaboration among CTSAs and across CTSA key function committees to address these weaknesses. We also requested that institutions send electronic copies of original RCR training materials to share among CTSAs via the CTSpedia website. Twenty institutions submitted at least one educational product. The CTSpedia now contains more than 90 RCR resources. PMID:20590680

  20. Immunology of Psoriasis

    PubMed Central

    Lowes, Michelle A.; Suárez-Fariñas, Mayte; Krueger, James G.

    2014-01-01

    The skin is the front line of defense against insult and injury and contains many epidermal and immune elements that comprise the skin-associated lymphoid tissue (SALT). The reaction of these components to injury allows an effective cutaneous response to restore homeostasis. Psoriasis vulgaris is the best-understood and most accessible human disease that is mediated by T cells and dendritic cells. Inflammatory myeloid dendritic cells release IL-23 and IL-12 to activate IL-17-producing T cells, Th1 cells, and Th22 cells to produce abundant psoriatic cytokines IL-17, IFN-γ, TNF, and IL-22. These cytokines mediate effects on keratinocytes to amplify psoriatic inflammation. Therapeutic studies with anticytokine antibodies have shown the importance of the key cytokines IL-23, TNF, and IL-17 in this process. We discuss the genetic background of psoriasis and its relationship to immune function, specifically genetic mutations, key PSORS loci, single nucleotide polymorphisms, and the skin transcriptome. The association between comorbidities and psoriasis is reviewed by correlating the skin transcriptome and serum proteins. Psoriasis-related cytokine-response pathways are considered in the context of the transcriptome of different mouse models. This approach offers a model for other inflammatory skin and autoimmune diseases. PMID:24655295

  1. The Role of Emotion in Musical Improvisation: An Analysis of Structural Features

    PubMed Central

    McPherson, Malinda J.; Lopez-Gonzalez, Monica; Rankin, Summer K.; Limb, Charles J.

    2014-01-01

    One of the primary functions of music is to convey emotion, yet how music accomplishes this task remains unclear. For example, simple correlations between mode (major vs. minor) and emotion (happy vs. sad) do not adequately explain the enormous range, subtlety or complexity of musically induced emotions. In this study, we examined the structural features of unconstrained musical improvisations generated by jazz pianists in response to emotional cues. We hypothesized that musicians would not utilize any universal rules to convey emotions, but would instead combine heterogeneous musical elements together in order to depict positive and negative emotions. Our findings demonstrate a lack of simple correspondence between emotions and musical features of spontaneous musical improvisation. While improvisations in response to positive emotional cues were more likely to be in major keys, have faster tempos, faster key press velocities and more staccato notes when compared to negative improvisations, there was a wide distribution for each emotion with components that directly violated these primary associations. The finding that musicians often combine disparate features together in order to convey emotion during improvisation suggests that structural diversity may be an essential feature of the ability of music to express a wide range of emotion. PMID:25144200

  2. Universal Health Coverage and the Right to Health: From Legal Principle to Post-2015 Indicators.

    PubMed

    Sridhar, Devi; McKee, Martin; Ooms, Gorik; Beiersmann, Claudia; Friedman, Eric; Gouda, Hebe; Hill, Peter; Jahn, Albrecht

    2015-01-01

    Universal Health Coverage (UHC) is widely considered one of the key components for the post-2015 health goal. The idea of UHC is rooted in the right to health, set out in the International Covenant on Economic, Social, and Cultural Rights. Based on the Covenant and the General Comment of the Committee on Economic, Social, and Cultural Rights, which is responsible for interpreting and monitoring the Covenant, we identify 6 key legal principles that should underpin UHC based on the right to health: minimum core obligation, progressive realization, cost-effectiveness, shared responsibility, participatory decision making, and prioritizing vulnerable or marginalized groups. Yet, although these principles are widely accepted, they are criticized for not being specific enough to operationalize as post-2015 indicators for reaching the target of UHC. In this article, we propose measurable and achievable indicators for UHC based on the right to health that can be used to inform the ongoing negotiations on Sustainable Development Goals. However, we identify 3 major challenges that face any exercise in setting indicators post-2015: data availability as an essential criterion, the universality of targets, and the adaptation of global goals to local populations. © SAGE Publications 2015.

  3. Instruction in the responsible conduct of research: an inventory of programs and materials within CTSAs.

    PubMed

    DuBois, James M; Schilling, Debie A; Heitman, Elizabeth; Steneck, Nicholas H; Kon, Alexander A

    2010-06-01

    The National Institutes of Health (NIH) require instruction in the responsible conduct of research (RCR) as a component of any Clinical and Translational Science Award (CTSA). The Educational Materials Group of the NIH CTSA Consortium's Clinical Research Ethics Key Function Committee (CRE-KFC) conducted a survey of the 38 institutions that held CTSA funding as of January 2009 to determine how they satisfy RCR training requirements. An 8-item questionnaire was sent by email to directors of the Clinical Research Ethics, the Educational and Career Development, and the Regulatory Knowledge cores. We received 78 completed surveys from 38 CTSAs (100%). We found that there is no unified approach to RCR training across CTSAs, many programs lack a coherent plan for RCR instruction, and most CTSAs have not developed unique instructional materials tailored to the needs of clinical and translational scientists. We recommend collaboration among CTSAs and across CTSA key function committees to address these weaknesses. We also requested that institutions send electronic copies of original RCR training materials to share among CTSAs via the CTSpedia website. Twenty institutions submitted at least one educational product. The CTSpedia now contains more than 90 RCR resources.

  4. Global analysis of gene expression in maize leaves treated with low temperature. II. Combined effect of severe cold (8 °C) and circadian rhythm.

    PubMed

    Jończyk, M; Sobkowiak, A; Trzcinska-Danielewicz, J; Skoneczny, M; Solecka, D; Fronk, J; Sowiński, P

    2017-10-01

    In maize seedlings, severe cold results in dysregulation of circadian pattern of gene expression causing profound modulation of transcription of genes related to photosynthesis and other key biological processes. Plants live highly cyclic life and their response to environmental stresses must allow for underlying biological rhythms. To study the interplay of a stress and a rhythmic cue we investigated transcriptomic response of maize seedlings to low temperature in the context of diurnal gene expression. Severe cold stress had pronounced effect on the circadian rhythm of a substantial proportion of genes. Their response was strikingly dual, comprising either flattening (partial or complete) of the diel amplitude or delay of expression maximum/minimum by several hours. Genes encoding central oscillator components behaved in the same dual manner, unlike their Arabidopsis counterparts reported earlier to cease cycling altogether upon cold treatment. Also numerous genes lacking circadian rhythm responded to the cold by undergoing up- or down-regulation. Notably, the transcriptome changes preceded major physiological manifestations of cold stress. In silico analysis of metabolic processes likely affected by observed gene expression changes indicated major down-regulation of photosynthesis, profound and multifarious modulation of plant hormone levels, and of chromatin structure, transcription, and translation. A role of trehalose and stachyose in cold stress signaling was also suggested. Meta-analysis of published transcriptomic data allowed discrimination between general stress response of maize and that unique to severe cold. Several cis- and trans-factors likely involved in the latter were predicted, albeit none of them seemed to have a major role. These results underscore a key role of modulation of diel gene expression in maize response to severe cold and the unique character of the cold-response of the maize circadian clock.

  5. Risk-assessment and risk-taking behavior predict potassium- and amphetamine-induced dopamine response in the dorsal striatum of rats

    PubMed Central

    Palm, Sara; Momeni, Shima; Lundberg, Stina; Nylander, Ingrid; Roman, Erika

    2014-01-01

    Certain personality types and behavioral traits display high correlations to drug use and an increased level of dopamine in the reward system is a common denominator of all drugs of abuse. Dopamine response to drugs has been suggested to correlate with some of these personality types and to be a key factor influencing the predisposition to addiction. This study investigated if behavioral traits can be related to potassium- and amphetamine-induced dopamine response in the dorsal striatum, an area hypothesized to be involved in the shift from drug use to addiction. The open field and multivariate concentric square field™ tests were used to assess individual behavior in male Wistar rats. Chronoamperometric recordings were then made to study the potassium- and amphetamine-induced dopamine response in vivo. A classification based on risk-taking behavior in the open field was used for further comparisons. Risk-taking behavior was correlated between the behavioral tests and high risk takers displayed a more pronounced response to the dopamine uptake blocking effects of amphetamine. Behavioral parameters from both tests could also predict potassium- and amphetamine-induced dopamine responses showing a correlation between neurochemistry and behavior in risk-assessment and risk-taking parameters. In conclusion, the high risk-taking rats showed a more pronounced reduction of dopamine uptake in the dorsal striatum after amphetamine indicating that this area may contribute to the sensitivity of these animals to psychostimulants and proneness to addiction. Further, inherent dopamine activity was related to risk-assessment behavior, which may be of importance for decision-making and inhibitory control, key components in addiction. PMID:25076877

  6. Development of an optimised key worker framework for people with dementia, their family and caring unit living in the community.

    PubMed

    Renehan, Emma; Goeman, Dianne; Koch, Susan

    2017-07-20

    In Australia, dementia is a national health priority. With the rising number of people living with dementia and shortage of formal and informal carers predicted in the near future, developing approaches to coordinating services in quality-focused ways is considered an urgent priority. Key worker support models are one approach that have been used to assist people living with dementia and their caring unit coordinate services and navigate service systems; however, there is limited literature outlining comprehensive frameworks for the implementation of community dementia key worker roles in practice. In this paper an optimised key worker framework for people with dementia, their family and caring unit living in the community is developed and presented. A number of processes were undertaken to inform the development of a co-designed optimised key worker framework: an expert working and reference group; a systematic review of the literature; and a qualitative evaluation of 14 dementia key worker models operating in Australia involving 14 interviews with organisation managers, 19 with key workers and 15 with people living with dementia and/or their caring unit. Data from the systematic review and evaluation of dementia key worker models were analysed by the researchers and the expert working and reference group using a constant comparative approach to define the essential components of the optimised framework. The developed framework consisted of four main components: overarching philosophies; organisational context; role definition; and key worker competencies. A number of more clearly defined sub-themes sat under each component. Reflected in the framework is the complexity of the dementia journey and the difficulty in trying to develop a 'one size fits all' approach. This co-designed study led to the development of an evidence based framework which outlines a comprehensive synthesis of components viewed as being essential to the implementation of a dementia key worker model of care in the community. The framework was informed and endorsed by people living with dementia and their caring unit, key workers, managers, Australian industry experts, policy makers and researchers. An evaluation of its effectiveness and relevance for practice within the dementia care space is required.

  7. Effects of Trait Self-Control on Response Conflict About Healthy and Unhealthy Food.

    PubMed

    Gillebaart, Marleen; Schneider, Iris K; De Ridder, Denise T D

    2016-12-01

    Self-control leads to positive life outcomes, but it is poorly understood. While previous research has focused on self-control failure, self-control success remains unexplored. The current studies aim to shed more light on the mechanisms of self-control by focusing on the resolution of response conflict as a key component in self-control success. Trait self-control was measured, and participants reported on the magnitude of response conflict they experienced about healthy and unhealthy foods in Study 1 (N = 146; M age  = 33.03; 59 females, 83 males, 4 unknown). The response conflict process was assessed in Study 2 (N = 118; M age  = 21.45; 68 females, 41 males, 9 unknown). Outcomes showed that self-reported evaluative response conflict about food items was smaller for people high in trait self-control. Study 2 revealed that higher trait self-control predicted faster resolution of self-control conflict, and an earlier peak of the response conflict. Taken together, these results provide insight into what makes people with high trait self-control successful, namely, how they handle response conflict. Implications for self-control theories and future directions are discussed. © 2015 Wiley Periodicals, Inc.

  8. Effect of Discontinuities and Uncertainties on the Response and Failure of Composite Structures

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K.; Perry, Ferman W.; Poteat, Marcia M. (Technical Monitor)

    2000-01-01

    The overall goal of this research was to assess the effect of discontinuities and uncertainties on the nonlinear response and failure of composite structures subjected to combined mechanical and thermal loads. The four key elements of the study were: (1) development of simple and efficient procedures for the accurate determination of transverse shear and transverse normal stresses in structural sandwiches as well as in unstiffened and stiffened composite panels and shells; (2) study the effects of transverse stresses on the response, damage initiation and propagation in composite and sandwich structures; (3) use of hierarchical sensitivity coefficients to identify the major parameters that affect the response and damage in each of the different levels in the hierarchy (micro-mechanical, layer, panel, subcomponent and component levels); and (4) application of fuzzy set techniques to identify the range and variation of possible responses. The computational models developed were used in conjunction with experiments, to understand the physical phenomena associated with the nonlinear response and failure of composite and sandwich structures. A toolkit was developed for use in conjunction with deterministic analysis programs to help the designer in assessing the effect of uncertainties in the different computational model parameters on the variability of the response quantities.

  9. TRIM-directed selective autophagy regulates immune activation.

    PubMed

    Kimura, Tomonori; Jain, Ashish; Choi, Seong Won; Mandell, Michael A; Johansen, Terje; Deretic, Vojo

    2017-05-04

    Selectivity of autophagy is achieved by target recognition; however, the number of autophagy receptors identified so far is limited. In this study we demonstrate that a subset of tripartite motif (TRIM) proteins mediate selective autophagy of key regulators of inflammatory signaling. MEFV/TRIM20, and TRIM21 act as autophagic receptors recognizing their cognate targets and delivering them for autophagic degradation. MEFV recognizes the inflammasome components NLRP3, CASP1 and NLRP1, whereas TRIM21 specifically recognizes the activated, dimeric from of IRF3 inducing type I interferon gene expression. MEFV and TRIM21 have a second activity, whereby they act not only as receptors but also recruit and organize key components of autophagic machinery consisting of ULK1, BECN1, ATG16L1, and mammalian homologs of Atg8, with a preference for GABARAP. MEFV capacity to organize the autophagy apparatus is affected by common mutations causing familial Mediterranean fever. These findings reveal a general mode of action of TRIMs as autophagic receptor-regulators performing a highly-selective type of autophagy (precision autophagy), with MEFV specializing in the suppression of inflammasome and CASP1 activation engendering IL1B/interleukin-1β production and implicated in the form of cell death termed pyroptosis, whereas TRIM21 dampens type I interferon responses.

  10. ChoiceKey: a real-time speech recognition program for psychology experiments with a small response set.

    PubMed

    Donkin, Christopher; Brown, Scott D; Heathcote, Andrew

    2009-02-01

    Psychological experiments often collect choice responses using buttonpresses. However, spoken responses are useful in many cases-for example, when working with special clinical populations, or when a paradigm demands vocalization, or when accurate response time measurements are desired. In these cases, spoken responses are typically collected using a voice key, which usually involves manual coding by experimenters in a tedious and error-prone manner. We describe ChoiceKey, an open-source speech recognition package for MATLAB. It can be optimized by training for small response sets and different speakers. We show ChoiceKey to be reliable with minimal training for most participants in experiments with two different responses. Problems presented by individual differences, and occasional atypical responses, are examined, and extensions to larger response sets are explored. The ChoiceKey source files and instructions may be downloaded as supplemental materials for this article from brm.psychonomic-journals.org/content/supplemental.

  11. Benchmarking surgeon satisfaction at academic health centers: a nationwide comparative survey.

    PubMed

    Drachman, D A

    1996-01-01

    Forty-six academic health centers (AHCs) belonging to the University HealthSystem consortium joined forces to compare the efficiency of their surgical services and to identify best practices. In addition to measures of operational performance, surgeon satisfaction with the surgical services provided was measured by using a standardized questionnaire. From hospital records, indicators of the efficiency of surgical services were collected in three main areas: scheduling, preoperative testing and assessment, and the intraoperative process. Responding to a mail questionnaire, a sample of surgeons rated their satisfaction with key aspects of surgical services including scheduling, operating room staff, and equipment/supplies. On the basis of a review of the operational measures and the survey results, high performers were identified. Site visits were made to several of these high performers to uncover the critical factors responsible for their success. The survey revealed distinct variations in surgeon satisfaction across the participating institutions. Numerical benchmarks were obtained for surgeon satisfaction with each key component of surgical services. Scheduling was the most important component of overall surgeon satisfaction, explaining 71% of the variance in the rating of overall satisfaction with surgical services. High operational efficiency and high surgeon satisfaction were not incompatible. Several of the participating institutions were able to achieve both. These results were disseminated to all of the participants at a national meeting as well as in written form. The surgeon satisfaction survey allowed the participants to establish benchmarks for surgeon satisfaction for each key component of the surgical services they receive. The site visits revealed several common characteristics of highly efficient surgical services. Taken by themselves, the participating institutions might have been reluctant to consider adopting these best practices for fear of alienating the surgical staff. The availability of data on surgeon satisfaction showed the participants that these best practices can coexist with high levels of surgeon satisfaction. This has helped to promote their adoption by the other participating institutions.

  12. Space Suit Portable Life Support System Test Bed (PLSS 1.0) Development and Testing

    NASA Technical Reports Server (NTRS)

    Watts, Carly; Campbell, Colin; Vogel, Matthew; Conger, Bruce

    2012-01-01

    A multi-year effort has been carried out at NASA-JSC to develop an advanced extra-vehicular activity Portable Life Support System (PLSS) design intended to further the current state of the art by increasing operational flexibility, reducing consumables, and increasing robustness. Previous efforts have focused on modeling and analyzing the advanced PLSS architecture, as well as developing key enabling technologies. Like the current International Space Station Extra-vehicular Mobility Unit PLSS, the advanced PLSS comprises three subsystems required to sustain the crew during extra-vehicular activity including the Thermal, Ventilation, and Oxygen Subsystems. This multi-year effort has culminated in the construction and operation of PLSS 1.0, a test bed that simulates full functionality of the advanced PLSS design. PLSS 1.0 integrates commercial off the shelf hardware with prototype technology development components, including the primary and secondary oxygen regulators, Ventilation Subsystem fan, Rapid Cycle Amine swingbed carbon dioxide and water vapor removal device, and Spacesuit Water Membrane Evaporator heat rejection device. The overall PLSS 1.0 test objective was to demonstrate the capability of the Advanced PLSS to provide key life support functions including suit pressure regulation, carbon dioxide and water vapor removal, thermal control and contingency purge operations. Supplying oxygen was not one of the specific life support functions because the PLSS 1.0 test was not oxygen rated. Nitrogen was used for the working gas. Additional test objectives were to confirm PLSS technology development components performance within an integrated test bed, identify unexpected system level interactions, and map the PLSS 1.0 performance with respect to key variables such as crewmember metabolic rate and suit pressure. Successful PLSS 1.0 testing completed 168 test points over 44 days of testing and produced a large database of test results that characterize system level and component performance. With the exception of several minor anomalies, the PLSS 1.0 test rig performed as expected; furthermore, many system responses trended in accordance with pre-test predictions.

  13. Research on criticality analysis method of CNC machine tools components under fault rate correlation

    NASA Astrophysics Data System (ADS)

    Gui-xiang, Shen; Xian-zhuo, Zhao; Zhang, Ying-zhi; Chen-yu, Han

    2018-02-01

    In order to determine the key components of CNC machine tools under fault rate correlation, a system component criticality analysis method is proposed. Based on the fault mechanism analysis, the component fault relation is determined, and the adjacency matrix is introduced to describe it. Then, the fault structure relation is hierarchical by using the interpretive structure model (ISM). Assuming that the impact of the fault obeys the Markov process, the fault association matrix is described and transformed, and the Pagerank algorithm is used to determine the relative influence values, combined component fault rate under time correlation can obtain comprehensive fault rate. Based on the fault mode frequency and fault influence, the criticality of the components under the fault rate correlation is determined, and the key components are determined to provide the correct basis for equationting the reliability assurance measures. Finally, taking machining centers as an example, the effectiveness of the method is verified.

  14. Reticular Formation and Pain: The Past and the Future

    PubMed Central

    Martins, Isabel; Tavares, Isaura

    2017-01-01

    The involvement of the reticular formation (RF) in the transmission and modulation of nociceptive information has been extensively studied. The brainstem RF contains several areas which are targeted by spinal cord afferents conveying nociceptive input. The arrival of nociceptive input to the RF may trigger alert reactions which generate a protective/defense reaction to pain. RF neurons located at the medulla oblongata and targeted by ascending nociceptive information are also involved in the control of vital functions that can be affected by pain, namely cardiovascular control. The RF contains centers that belong to the pain modulatory system, namely areas involved in bidirectional balance (decrease or enhancement) of pain responses. It is currently accepted that the imbalance of pain modulation towards pain facilitation accounts for chronic pain. The medullary RF has the peculiarity of harboring areas involved in bidirectional pain control namely by the existence of specific neuronal populations involved in antinociceptive or pronociceptive behavioral responses, namely at the rostroventromedial medulla (RVM) and the caudal ventrolateral medulla (VLM). Furthermore the dorsal reticular nucleus (also known as subnucleus reticularis dorsalis; DRt) may enhance nociceptive responses, through a reverberative circuit established with spinal lamina I neurons and inhibit wide-dynamic range (WDR) neurons of the deep dorsal horn. The components of the triad RVM-VLM-DRt are reciprocally connected and represent a key gateway for top-down pain modulation. The RVM-VLM-DRt triad also represents the neurobiological substrate for the emotional and cognitive modulation of pain, through pathways that involve the periaqueductal gray (PAG)-RVM connection. Collectively, we propose that the RVM-VLM-DRt triad represents a key component of the “dynamic pain connectome” with special features to provide integrated and rapid responses in situations which are life-threatening and involve pain. The new available techniques in neurobiological studies both in animal and human studies are producing new and fascinating data which allow to understand the complex role of the RF in pain modulation and its integration with several body functions and also how the RF accounts for chronic pain. PMID:28725185

  15. Reticular Formation and Pain: The Past and the Future.

    PubMed

    Martins, Isabel; Tavares, Isaura

    2017-01-01

    The involvement of the reticular formation (RF) in the transmission and modulation of nociceptive information has been extensively studied. The brainstem RF contains several areas which are targeted by spinal cord afferents conveying nociceptive input. The arrival of nociceptive input to the RF may trigger alert reactions which generate a protective/defense reaction to pain. RF neurons located at the medulla oblongata and targeted by ascending nociceptive information are also involved in the control of vital functions that can be affected by pain, namely cardiovascular control. The RF contains centers that belong to the pain modulatory system, namely areas involved in bidirectional balance (decrease or enhancement) of pain responses. It is currently accepted that the imbalance of pain modulation towards pain facilitation accounts for chronic pain. The medullary RF has the peculiarity of harboring areas involved in bidirectional pain control namely by the existence of specific neuronal populations involved in antinociceptive or pronociceptive behavioral responses, namely at the rostroventromedial medulla (RVM) and the caudal ventrolateral medulla (VLM). Furthermore the dorsal reticular nucleus (also known as subnucleus reticularis dorsalis; DRt) may enhance nociceptive responses, through a reverberative circuit established with spinal lamina I neurons and inhibit wide-dynamic range (WDR) neurons of the deep dorsal horn. The components of the triad RVM-VLM-DRt are reciprocally connected and represent a key gateway for top-down pain modulation. The RVM-VLM-DRt triad also represents the neurobiological substrate for the emotional and cognitive modulation of pain, through pathways that involve the periaqueductal gray (PAG)-RVM connection. Collectively, we propose that the RVM-VLM-DRt triad represents a key component of the "dynamic pain connectome" with special features to provide integrated and rapid responses in situations which are life-threatening and involve pain. The new available techniques in neurobiological studies both in animal and human studies are producing new and fascinating data which allow to understand the complex role of the RF in pain modulation and its integration with several body functions and also how the RF accounts for chronic pain.

  16. Fire ant venom alkaloids act as key attractants for the parasitic phorid fly, Pseudacteon tricuspis (Diptera: Phoridae).

    PubMed

    Chen, Li; Sharma, Kavita R; Fadamiro, Henry Y

    2009-12-01

    The phorid fly, Pseudacteon tricuspis Borgmeier, is an introduced parasitoid of imported fire ants, Solenopsis spp., in the USA. Although the assumption that phorid flies use fire ant alarm pheromones for host location is probably true, we demonstrated in a previous study the possible involvement of other ant semiochemicals in the response of P. tricuspis to fire ants. This study was conducted to determine the glandular sources and identity of the semiochemicals mediating this interaction. First, we tested the electroantennogram response of P. tricuspis to extracts of key body parts and glands of workers of the red imported fire ant, S. invicta Buren. The results confirm that the poison (venom) gland/sac is the key source of compounds which elicited strong antennal activity in P. tricuspis. Follow-up studies were conducted by using a combination of bioassay-guided fractionation and behavioral bioassays to test the hypothesis that attraction of this parasitoid to fire ants is mediated by venom alkaloids. The results confirm the response of P. tricuspis to physiologically relevant amounts of the two venom alkaloid fractions (cis and trans alkaloid fractions) of S. invicta. Further analysis by coupled gas chromatography-electroantennogram detection revealed nine venom alkaloid components including two novel 2,6-dialkylpiperideines that elicited significant antennal activity in P. tricuspis. This is the first demonstration of the role of venom alkaloids of ants as attractants for their natural enemies. We propose a semiochemical-mediated host location mechanism for P. tricuspis involving both alarm pheromones and venom alkaloids. The ecological significance of these findings, including the attraction of male P. tricuspis to fire ant venom alkaloids, possibly for mate location, is discussed.

  17. Uncertainty Quantification for CO2-Enhanced Oil Recovery

    NASA Astrophysics Data System (ADS)

    Dai, Z.; Middleton, R.; Bauman, J.; Viswanathan, H.; Fessenden-Rahn, J.; Pawar, R.; Lee, S.

    2013-12-01

    CO2-Enhanced Oil Recovery (EOR) is currently an option for permanently sequestering CO2 in oil reservoirs while increasing oil/gas productions economically. In this study we have developed a framework for understanding CO2 storage potential within an EOR-sequestration environment at the Farnsworth Unit of the Anadarko Basin in northern Texas. By coupling a EOR tool--SENSOR (CEI, 2011) with a uncertainty quantification tool PSUADE (Tong, 2011), we conduct an integrated Monte Carlo simulation of water, oil/gas components and CO2 flow and reactive transport in the heterogeneous Morrow formation to identify the key controlling processes and optimal parameters for CO2 sequestration and EOR. A global sensitivity and response surface analysis are conducted with PSUADE to build numerically the relationship among CO2 injectivity, oil/gas production, reservoir parameters and distance between injection and production wells. The results indicate that the reservoir permeability and porosity are the key parameters to control the CO2 injection, oil and gas (CH4) recovery rates. The distance between the injection and production wells has large impact on oil and gas recovery and net CO2 injection rates. The CO2 injectivity increases with the increasing reservoir permeability and porosity. The distance between injection and production wells is the key parameter for designing an EOR pattern (such as a five (or nine)-spot pattern). The optimal distance for a five-spot-pattern EOR in this site is estimated from the response surface analysis to be around 400 meters. Next, we are building the machinery into our risk assessment framework CO2-PENS to utilize these response surfaces and evaluate the operation risk for CO2 sequestration and EOR at this site.

  18. On performance of parametric and distribution-free models for zero-inflated and over-dispersed count responses.

    PubMed

    Tang, Wan; Lu, Naiji; Chen, Tian; Wang, Wenjuan; Gunzler, Douglas David; Han, Yu; Tu, Xin M

    2015-10-30

    Zero-inflated Poisson (ZIP) and negative binomial (ZINB) models are widely used to model zero-inflated count responses. These models extend the Poisson and negative binomial (NB) to address excessive zeros in the count response. By adding a degenerate distribution centered at 0 and interpreting it as describing a non-risk group in the population, the ZIP (ZINB) models a two-component population mixture. As in applications of Poisson and NB, the key difference between ZIP and ZINB is the allowance for overdispersion by the ZINB in its NB component in modeling the count response for the at-risk group. Overdispersion arising in practice too often does not follow the NB, and applications of ZINB to such data yield invalid inference. If sources of overdispersion are known, other parametric models may be used to directly model the overdispersion. Such models too are subject to assumed distributions. Further, this approach may not be applicable if information about the sources of overdispersion is unavailable. In this paper, we propose a distribution-free alternative and compare its performance with these popular parametric models as well as a moment-based approach proposed by Yu et al. [Statistics in Medicine 2013; 32: 2390-2405]. Like the generalized estimating equations, the proposed approach requires no elaborate distribution assumptions. Compared with the approach of Yu et al., it is more robust to overdispersed zero-inflated responses. We illustrate our approach with both simulated and real study data. Copyright © 2015 John Wiley & Sons, Ltd.

  19. A novel property of DNA - as a bioflotation reagent in mineral processing.

    PubMed

    Vasanthakumar, Balasubramanian; Ravishankar, Honnavar; Subramanian, Sankaran

    2012-01-01

    Environmental concerns regarding the use of certain chemicals in the froth flotation of minerals have led investigators to explore biological entities as potential substitutes for the reagents in vogue. Despite the fact that several microorganisms have been used for the separation of a variety of mineral systems, a detailed characterization of the biochemical molecules involved therein has not been reported so far. In this investigation, the selective flotation of sphalerite from a sphalerite-galena mineral mixture has been achieved using the cellular components of Bacillus species. The key constituent primarily responsible for the flotation of sphalerite has been identified as DNA, which functions as a bio-collector. Furthermore, using reconstitution studies, the obligatory need for the presence of non-DNA components as bio-depressants for galena has been demonstrated. A probable model involving these entities in the selective flotation of sphalerite from the mineral mixture has been discussed.

  20. A Novel Property of DNA – As a Bioflotation Reagent in Mineral Processing

    PubMed Central

    Vasanthakumar, Balasubramanian; Ravishankar, Honnavar; Subramanian, Sankaran

    2012-01-01

    Environmental concerns regarding the use of certain chemicals in the froth flotation of minerals have led investigators to explore biological entities as potential substitutes for the reagents in vogue. Despite the fact that several microorganisms have been used for the separation of a variety of mineral systems, a detailed characterization of the biochemical molecules involved therein has not been reported so far. In this investigation, the selective flotation of sphalerite from a sphalerite-galena mineral mixture has been achieved using the cellular components of Bacillus species. The key constituent primarily responsible for the flotation of sphalerite has been identified as DNA, which functions as a bio-collector. Furthermore, using reconstitution studies, the obligatory need for the presence of non-DNA components as bio-depressants for galena has been demonstrated. A probable model involving these entities in the selective flotation of sphalerite from the mineral mixture has been discussed. PMID:22768298

  1. Activation and synchronization of the oscillatory morphodynamics in multicellular monolayer

    PubMed Central

    Lin, Shao-Zhen; Li, Bo; Lan, Ganhui; Feng, Xi-Qiao

    2017-01-01

    Oscillatory morphodynamics provides necessary mechanical cues for many multicellular processes. Owing to their collective nature, these processes require robustly coordinated dynamics of individual cells, which are often separated too distantly to communicate with each other through biomaterial transportation. Although it is known that the mechanical balance generally plays a significant role in the systems’ morphologies, it remains elusive whether and how the mechanical components may contribute to the systems’ collective morphodynamics. Here, we study the collective oscillations in the Drosophila amnioserosa tissue to elucidate the regulatory roles of the mechanical components. We identify that the tensile stress is the key activator that switches the collective oscillations on and off. This regulatory role is shown analytically using the Hopf bifurcation theory. We find that the physical properties of the tissue boundary are directly responsible for synchronizing the oscillatory intensity and polarity of all inner cells and for orchestrating the spatial oscillation patterns inthe tissue. PMID:28716911

  2. Innate immunity in vertebrates: an overview.

    PubMed

    Riera Romo, Mario; Pérez-Martínez, Dayana; Castillo Ferrer, Camila

    2016-06-01

    Innate immunity is a semi-specific and widely distributed form of immunity, which represents the first line of defence against pathogens. This type of immunity is critical to maintain homeostasis and prevent microbe invasion, eliminating a great variety of pathogens and contributing with the activation of the adaptive immune response. The components of innate immunity include physical and chemical barriers, humoral and cell-mediated components, which are present in all jawed vertebrates. The understanding of innate defence mechanisms in non-mammalian vertebrates is the key to comprehend the general picture of vertebrate innate immunity and its evolutionary history. This is also essential for the identification of new molecules with applications in immunopharmacology and immunotherapy. In this review, we describe and discuss the main elements of vertebrate innate immunity, presenting core findings in this field and identifying areas that need further investigation. © 2016 John Wiley & Sons Ltd.

  3. Adult Attachment Styles Associated with Brain Activity in Response to Infant Faces in Nulliparous Women: An Event-Related Potentials Study.

    PubMed

    Ma, Yuanxiao; Ran, Guangming; Chen, Xu; Ma, Haijing; Hu, Na

    2017-01-01

    Adult attachment style is a key for understanding emotion regulation and feelings of security in human interactions as well as for the construction of the caregiving system. The caregiving system is a group of representations about affiliative behaviors, which is guided by the caregiver's sensitivity and empathy, and is mature in young adulthood. Appropriate perception and interpretation of infant emotions is a crucial component of the formation of a secure attachment relationship between infant and caregiver. As attachment styles influence the ways in which people perceive emotional information, we examined how different attachment styles associated with brain response to the perception of infant facial expressions in nulliparous females with secure, anxious, and avoidant attachment styles. The event-related potentials of 65 nulliparous females were assessed during a facial recognition task with joy, neutral, and crying infant faces. The results showed that anxiously attached females exhibited larger N170 amplitudes than those with avoidant attachment in response to all infant faces. Regarding the P300 component, securely attached females showed larger amplitudes to all infant faces in comparison with avoidantly attached females. Moreover, anxiously attached females exhibited greater amplitudes than avoidantly attached females to only crying infant faces. In conclusion, the current results provide evidence that attachment style differences are associated with brain responses to the perception of infant faces. Furthermore, these findings further separate the psychological mechanisms underlying the caregiving behavior of those with anxious and avoidant attachment from secure attachment.

  4. Recent insights into physiological responses to nutrients by the cylindrospermopsin producing cyanobacterium, Cylindrospermopsis raciborskii

    NASA Astrophysics Data System (ADS)

    Burford, Michele A.; Willis, Anusuya; Chuang, Ann; Man, Xiao; Orr, Phil

    2017-11-01

    The harmful cyanobacterium Cylindrospermopsis raciborskii is a widespread species increasingly being recorded in freshwater systems around the world. Studies have demonstrated some key attributes of this species which may explain its global dominance. It has a high level of flexibility with respect to light and nutrients, being capable of growth under low and variable light conditions. However, it is the strategy with respect to nutrient utilization that has received more attention. Unlike many bloom forming species, the dominance of this species is not simply linked to higher nutrient loads. In fact it appears that it is more competitive when phosphorus and nitrogen availability is low and/or variable. An important component of this flexibility appears to be the result of within-population strain variability in responses to nutrients, as well as key physiological adaptations. Strain variability also appears to have an effect on the population-level cell quota of toxins, specifically cylindrospermopsins (CYNs). Field studies in Australia showed that populations had the highest proportion of toxic strains when dissolved inorganic phosphorus was added, resulting in stoichiometrically balanced nitrogen and phosphorus within the cells. These strategies are part of an arsenal of responses to environmental conditions, making it a challenging species to manage. However, our ability to improve bloom prediction will rely on a more detailed understanding of the complex physiology and ecology of this species.

  5. Temperatures and the growth and development of maize and rice: a review.

    PubMed

    Sánchez, Berta; Rasmussen, Anton; Porter, John R

    2014-02-01

    Because of global land surface warming, extreme temperature events are expected to occur more often and more intensely, affecting the growth and development of the major cereal crops in several ways, thus affecting the production component of food security. In this study, we have identified rice and maize crop responses to temperature in different, but consistent, phenological phases and development stages. A literature review and data compilation of around 140 scientific articles have determined the key temperature thresholds and response to extreme temperature effects for rice and maize, complementing an earlier study on wheat. Lethal temperatures and cardinal temperatures, together with error estimates, have been identified for phenological phases and development stages. Following the methodology of previous work, we have collected and statistically analysed temperature thresholds of the three crops for the key physiological processes such as leaf initiation, shoot growth and root growth and for the most susceptible phenological phases such as sowing to emergence, anthesis and grain filling. Our summary shows that cardinal temperatures are conservative between studies and are seemingly well defined in all three crops. Anthesis and ripening are the most sensitive temperature stages in rice as well as in wheat and maize. We call for further experimental studies of the effects of transgressing threshold temperatures so such responses can be included into crop impact and adaptation models. © 2013 John Wiley & Sons Ltd.

  6. Electronic Voting Protocol Using Identity-Based Cryptography.

    PubMed

    Gallegos-Garcia, Gina; Tapia-Recillas, Horacio

    2015-01-01

    Electronic voting protocols proposed to date meet their properties based on Public Key Cryptography (PKC), which offers high flexibility through key agreement protocols and authentication mechanisms. However, when PKC is used, it is necessary to implement Certification Authority (CA) to provide certificates which bind public keys to entities and enable verification of such public key bindings. Consequently, the components of the protocol increase notably. An alternative is to use Identity-Based Encryption (IBE). With this kind of cryptography, it is possible to have all the benefits offered by PKC, without neither the need of certificates nor all the core components of a Public Key Infrastructure (PKI). Considering the aforementioned, in this paper we propose an electronic voting protocol, which meets the privacy and robustness properties by using bilinear maps.

  7. Electronic Voting Protocol Using Identity-Based Cryptography

    PubMed Central

    Gallegos-Garcia, Gina; Tapia-Recillas, Horacio

    2015-01-01

    Electronic voting protocols proposed to date meet their properties based on Public Key Cryptography (PKC), which offers high flexibility through key agreement protocols and authentication mechanisms. However, when PKC is used, it is necessary to implement Certification Authority (CA) to provide certificates which bind public keys to entities and enable verification of such public key bindings. Consequently, the components of the protocol increase notably. An alternative is to use Identity-Based Encryption (IBE). With this kind of cryptography, it is possible to have all the benefits offered by PKC, without neither the need of certificates nor all the core components of a Public Key Infrastructure (PKI). Considering the aforementioned, in this paper we propose an electronic voting protocol, which meets the privacy and robustness properties by using bilinear maps. PMID:26090515

  8. Innovative Educational Restructuring for America 2000: Time To Bury Political Bureaucracies and Begin Systematic Assessment, Profiling & Technological Improvement of School Organizations.

    ERIC Educational Resources Information Center

    Packard, Richard D.; Dereshiwsky, Mary I.

    Despite current interest with the concept of the "New American School" model discussed in "America 2000," school systems continue to approach educational reform and restructuring by tinkering with key organizational components in isolation. The total school organization requires assessment and profiling to determine which key components are drags…

  9. [Testing method research for key performance indicator of imaging acousto-optic tunable filter (AOTF)].

    PubMed

    Hu, Shan-Zhou; Chen, Fen-Fei; Zeng, Li-Bo; Wu, Qiong-Shui

    2013-01-01

    Imaging AOTF is an important optical filter component for new spectral imaging instruments developed in recent years. The principle of imaging AOTF component was demonstrated, and a set of testing methods for some key performances were studied, such as diffraction efficiency, wavelength shift with temperature, homogeneity in space for diffraction efficiency, imaging shift, etc.

  10. Does grazing of cover crops impact biologically active soil C and N fractions under inversion and no tillage management

    USDA-ARS?s Scientific Manuscript database

    Cover crops are a key component of conservation cropping systems. They can also be a key component of integrated crop-livestock systems by offering high-quality forage during short periods between cash crops. The impact of cattle grazing on biologically active soil C and N fractions has not receiv...

  11. Gender-Mainstreaming in Technical and Vocational Education and Training

    NASA Astrophysics Data System (ADS)

    Nurhaeni, I. D. A.; Kurniawan, Y.

    2018-02-01

    Gender differences should be considered in vocational high schools so women and men can develop their potentials without being inhibited by gender bias. Gender mainstreaming in vocational high schools is a strategy to integrate gender differences at all stages in teaching-learning process for achieving gender equality and equity. This research evaluates the implementation of gender mainstreaming in vocational high schools consisting of seven key components of gender mainstreaming. Four vocational high schools in Sragen Regency Indonesia have been purposively selected. The data were obtained through in-depth interviews and documentation studies. The data were analyzed using Kabeer’s model of gender analysis. The findings show that not all key components of gender mainstreaming have been implemented in vocational high schools. Most vocational high schools have implemented three of seven key components of gender mainstreaming, namely political will and leadership, policy framework and gender statistics. Meanwhile four of seven key components of gender mainstreaming, namely structure and mechanism, resources, infra structures and civil society have not been well-implemented. In conclusion gender mainstreaming has not been implemented effectively in vocational high schools. Accordingly, the government’s education office should continue to encourage and publish guidelines on the implementation of gender-mainstreaming in vocational high schools.

  12. In vivo quantitative analysis of Talin turnover in response to force

    PubMed Central

    Hákonardóttir, Guðlaug Katrín; López-Ceballos, Pablo; Herrera-Reyes, Alejandra Donají; Das, Raibatak; Coombs, Daniel; Tanentzapf, Guy

    2015-01-01

    Cell adhesion to the extracellular matrix (ECM) allows cells to form and maintain three-dimensional tissue architecture. Cell–ECM adhesions are stabilized upon exposure to mechanical force. In this study, we used quantitative imaging and mathematical modeling to gain mechanistic insight into how integrin-based adhesions respond to increased and decreased mechanical forces. A critical means of regulating integrin-based adhesion is provided by modulating the turnover of integrin and its adhesion complex (integrin adhesion complex [IAC]). The turnover of the IAC component Talin, a known mechanosensor, was analyzed using fluorescence recovery after photobleaching. Experiments were carried out in live, intact flies in genetic backgrounds that increased or decreased the force applied on sites of adhesion. This analysis showed that when force is elevated, the rate of assembly of new adhesions increases such that cell–ECM adhesion is stabilized. Moreover, under conditions of decreased force, the overall rate of turnover, but not the proportion of adhesion complex components undergoing turnover, increases. Using point mutations, we identify the key functional domains of Talin that mediate its response to force. Finally, by fitting a mathematical model to the data, we uncover the mechanisms that mediate the stabilization of ECM-based adhesion during development. PMID:26446844

  13. Mitochondrial peptides modulate mitochondrial function during cellular senescence.

    PubMed

    Kim, Su-Jeong; Mehta, Hemal H; Wan, Junxiang; Kuehnemann, Chisaka; Chen, Jingcheng; Hu, Ji-Fan; Hoffman, Andrew R; Cohen, Pinchas

    2018-06-10

    Cellular senescence is a complex cell fate response that is thought to underlie several age-related pathologies. Despite a loss of proliferative potential, senescent cells are metabolically active and produce energy-consuming effectors, including senescence-associated secretory phenotypes (SASPs). Mitochondria play crucial roles in energy production and cellular signaling, but the key features of mitochondrial physiology and particularly of mitochondria-derived peptides (MDPs), remain underexplored in senescence responses. Here, we used primary human fibroblasts made senescent by replicative exhaustion, doxorubicin or hydrogen peroxide treatment, and examined the number of mitochondria and the levels of mitochondrial respiration, mitochondrial DNA methylation and the mitochondria-encoded peptides humanin, MOTS-c, SHLP2 and SHLP6. Senescent cells showed increased numbers of mitochondria and higher levels of mitochondrial respiration, variable changes in mitochondrial DNA methylation, and elevated levels of humanin and MOTS-c. Humanin and MOTS-c administration modestly increased mitochondrial respiration and selected components of the SASP in doxorubicin-induced senescent cells partially via JAK pathway. Targeting metabolism in senescence cells is an important strategy to reduce SASP production for eliminating the deleterious effects of senescence. These results provide insight into the role of MDPs in mitochondrial energetics and the production of SASP components by senescent cells.

  14. On the Nature of QPO Phase Lags in Black Hole Candidates

    NASA Technical Reports Server (NTRS)

    Shaposhnikov, Nikolai

    2012-01-01

    Observations of quasi-periodic oscillations (QPOs) in X-ray binaries hold a key to understanding many aspects of these enigmatic systems. Complex appearance of the Fourier phase lags related to QPOs is one of the most puzzling observational effects in accreting black holes. In this Letter we show that QPO properties, including phase lags, can be explained in a framework of a simple scenario, where the oscillating media provides a feedback on the emerging spectrum. We demonstrate that the QPO waveform is presented by the product of a perturbation and a time delayed response factors, where the response is energy dependent. The essential property of this effect is its non-linear and multiplicative nature. Our multiplicative reverberation model successfully describes the QPO components in energy dependent power spectra as well as the appearance of the phase lags between signal in different energy bands. We apply our model to QPOs observed by Rossi X-ray Timing Explorer in BH candidate XTE J1550-564. We briefly discuss the implications of the observed energy dependence of the QPO reverberation times and amplitudes to the nature of the power law spectral component and its variability.

  15. Basic Fibroblast Growth Factor Activates Serum Response Factor Gene Expression by Multiple Distinct Signaling Mechanisms

    PubMed Central

    Spencer, Jeffrey A.; Major, Michael L.; Misra, Ravi P.

    1999-01-01

    Serum response factor (SRF) plays a central role in the transcriptional response of mammalian cells to a variety of extracellular signals. It is a key regulator of many cellular early response genes which are believed to be involved in cell growth and differentiation. The mechanism by which SRF activates transcription in response to mitogenic agents has been extensively studied; however, significantly less is known about regulation of the SRF gene itself. Previously, we identified distinct regulatory elements in the SRF promoter that play a role in activation, including a consensus ETS domain binding site, a consensus overlapping Sp/Egr-1 binding site, and two SRF binding sites. We further showed that serum induces SRF by a mechanism that requires an intact SRF binding site, also termed a CArG box. In the present study we demonstrate that in response to stimulation of cells by a purified growth factor, basic fibroblast growth factor (bFGF), the SRF promoter is upregulated by a complex pathway that involves at least two independent mechanisms: a CArG box-independent mechanism that is mediated by an ETS binding site, and a novel CArG box-dependent mechanism that requires both an Sp factor binding site and the CArG motifs for maximal stimulation. Our analysis indicates that the CArG/Sp element activation mechanism is mediated by distinct signaling pathways. The CArG box-dependent component is targeted by a Rho-mediated pathway, and the Sp binding site-dependent component is targeted by a Ras-mediated pathway. Both SRF and bFGF have been implicated in playing an important role in mediating cardiogenesis during development. The implications of our findings for SRF expression during development are discussed. PMID:10330138

  16. Dysfunctional stress responses in chronic pain.

    PubMed

    Woda, Alain; Picard, Pascale; Dutheil, Frédéric

    2016-09-01

    Many dysfunctional and chronic pain conditions overlap. This review describes the different modes of chronic deregulation of the adaptive response to stress which may be a common factor for these conditions. Several types of dysfunction can be identified within the hypothalamo-pituitary-adrenal axis: basal hypercortisolism, hyper-reactivity, basal hypocortisolism and hypo-reactivity. Neuroactive steroid synthesis is another component of the adaptive response to stress. Dehydroepiandrosterone (DHEA) and its sulfated form DHEA-S, and progesterone and its derivatives are synthetized in cutaneous, nervous, and adipose cells. They are neuroactive factors that act locally. They may have a role in the localization of the symptoms and their levels can vary both in the central nervous system and in the periphery. Persistent changes in neuroactive steroid levels or precursors can induce localized neurodegeneration. The autonomic nervous system is another component of the stress response. Its dysfunction in chronic stress responses can be expressed by decreased basal parasympathethic activity, increased basal sympathetic activity or sympathetic hyporeactivity to a stressful stimulus. The immune and genetic systems also participate. The helper-T cells Th1 secrete pro-inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF-α, whereas Th2 secrete anti-inflammatory cytokines: IL-4, IL-10, IGF-10, IL-13. Chronic deregulation of the Th1/Th2 balance can occur in favor of anti- or pro-inflammatory direction, locally or systemically. Individual vulnerability to stress can be due to environmental factors but can also be genetically influenced. Genetic polymorphisms and epigenetics are the main keys to understanding the influence of genetics on the response of individuals to constraints. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Alert Notification System Router

    NASA Technical Reports Server (NTRS)

    Gurganus, Joseph; Carey, Everett; Antonucci, Robert; Hitchener, Peter

    2009-01-01

    The Alert Notification System Router (ANSR) software provides satellite operators with notifications of key events through pagers, cell phones, and e-mail. Written in Java, this application is specifically designed to meet the mission-critical standards for mission operations while operating on a variety of hardware environments. ANSR is a software component that runs inside the Mission Operations Center (MOC). It connects to the mission's message bus using the GMSEC [Goddard Space Flight Center (GSFC) Mission Services Evolution Center (GMSEC)] standard. Other components, such as automation and monitoring components, can use ANSR to send directives to notify users or groups. The ANSR system, in addition to notifying users, can check for message acknowledgements from a user and escalate the notification to another user if there is no acknowledgement. When a firewall prevents ANSR from accessing the Internet directly, proxies can be run on the other side of the wall. These proxies can be configured to access the Internet, notify users, and poll for their responses. Multiple ANSRs can be run in parallel, providing a seamless failover capability in the event that one ANSR system becomes incapacitated.

  18. Type II protein arginine methyltransferase 5 (PRMT5) is required for circadian period determination in Arabidopsis thaliana.

    PubMed

    Hong, Sunghyun; Song, Hae-Ryong; Lutz, Kerry; Kerstetter, Randall A; Michael, Todd P; McClung, C Robertson

    2010-12-07

    Posttranslational modification is an important element in circadian clock function from cyanobacteria through plants and mammals. For example, a number of key clock components are phosphorylated and thereby marked for subsequent ubiquitination and degradation. Through forward genetic analysis we demonstrate that protein arginine methyltransferase 5 (PRMT5; At4g31120) is a critical determinant of circadian period in Arabidopsis. PRMT5 is coregulated with a set of 1,253 genes that shows alterations in phase of expression in response to entrainment to thermocycles versus photocycles in constant temperature. PRMT5 encodes a type II protein arginine methyltransferase that catalyzes the symmetric dimethylation of arginine residues (Rsme2). Rsme2 modification has been observed in many taxa, and targets include histones, components of the transcription complex, and components of the spliceosome. Neither arginine methylation nor PRMT5 has been implicated previously in circadian clock function, but the period lengthening associated with mutational disruption of prmt5 indicates that Rsme2 is a decoration important for the Arabidopsis clock and possibly for clocks in general.

  19. Structural and mechanical heterogeneity of the erythrocyte membrane reveals hallmarks of membrane stability.

    PubMed

    Picas, Laura; Rico, Félix; Deforet, Maxime; Scheuring, Simon

    2013-02-26

    The erythrocyte membrane, a metabolically regulated active structure that comprises lipid molecules, junctional complexes, and the spectrin network, enables the cell to undergo large passive deformations when passing through the microvascular system. Here we use atomic force microscopy (AFM) imaging and quantitative mechanical mapping at nanometer resolution to correlate structure and mechanics of key components of the erythrocyte membrane, crucial for cell integrity and function. Our data reveal structural and mechanical heterogeneity modulated by the metabolic state at unprecedented nanometer resolution. ATP-depletion, reducing skeletal junction phosphorylation in RBC cells, leads to membrane stiffening. Analysis of ghosts and shear-force opened erythrocytes show that, in the absence of cytosolic kinases, spectrin phosphorylation results in membrane stiffening at the extracellular face and a reduced junction remodeling in response to loading forces. Topography and mechanical mapping of single components at the cytoplasmic face reveal that, surprisingly, spectrin phosphorylation by ATP softens individual filaments. Our findings suggest that, besides the mechanical signature of each component, the RBC membrane mechanics is regulated by the metabolic state and the assembly of its structural elements.

  20. Receptor chirality and behavioral specificity of the boll weevil,Anthonomus grandis Boh. (Coleoptera: Curculionidae), for its pheromone, (+)-grandisol.

    PubMed

    Dickens, J C; Mori, K

    1989-02-01

    Electrophysiological recordings from antennal olfactory receptors and field behavioral experiments showed both male and female boll weevils,Anthonomus grandis Boh. (Coleoptera: Curculionidae), to respond specifically to (+)-grandisol, an enantiomer of compound I of the boll weevil aggregation pheromone. Single-cell recordings revealed antennal olfactory neurons in both male and female weevils keyed to (+)-grandisol. Electroantennograms in response to serial dilutions of the grandisol enaniiomers showed a threshold 100 to 1000 times lower for (+)-grandisol relative to its antipode. In field behavioral experiments, both sexes were significantly more attracted to (+)-grandisol in combination with the three other pheromone components than the combination with (-)-grandisol. When (-)-grandisol was placed with the (+)-enantiomer at equal dosages, a slight although statistically insignificant inhibition occurred. Subsequent field tests showed that the low level of attraction exhibited by (-)-grandisol in combination with the other three pheromone components could be attributed to the other three components alone. These results are in contrast with an earlier study, which found (-)-grandisol to be as attractive as the (+)-enantiomer.

  1. Programmable 3D silk bone marrow niche for platelet generation ex vivo and modeling of megakaryopoiesis pathologies

    PubMed Central

    Di Buduo, Christian A.; Wray, Lindsay S.; Tozzi, Lorenzo; Malara, Alessandro; Chen, Ying; Ghezzi, Chiara E.; Smoot, Daniel; Sfara, Carla; Antonelli, Antonella; Spedden, Elise; Bruni, Giovanna; Staii, Cristian; De Marco, Luigi; Magnani, Mauro; Kaplan, David L.

    2015-01-01

    We present a programmable bioengineered 3-dimensional silk-based bone marrow niche tissue system that successfully mimics the physiology of human bone marrow environment allowing us to manufacture functional human platelets ex vivo. Using stem/progenitor cells, megakaryocyte function and platelet generation were recorded in response to variations in extracellular matrix components, surface topography, stiffness, coculture with endothelial cells, and shear forces. Millions of human platelets were produced and showed to be functional based on multiple activation tests. Using adult hematopoietic progenitor cells our system demonstrated the ability to reproduce key steps of thrombopoiesis, including alterations observed in diseased states. A critical feature of the system is the use of natural silk protein biomaterial allowing us to leverage its biocompatibility, nonthrombogenic features, programmable mechanical properties, and surface binding of cytokines, extracellular matrix components, and endothelial-derived proteins. This in turn offers new opportunities for the study of blood component production ex vivo and provides a superior tissue system for the study of pathologic mechanisms of human platelet production. PMID:25575540

  2. The plant cell nucleus: a true arena for the fight between plants and pathogens.

    PubMed

    Deslandes, Laurent; Rivas, Susana

    2011-01-01

    Communication between the cytoplasm and the nucleus is a fundamental feature shared by both plant and animal cells. Cellular factors involved in the transport of macromolecules through the nuclear envelope, including nucleoporins, importins and Ran-GTP related components, are conserved among a variety of eukaryotic systems. Interestingly, mutations in these nuclear components compromise resistance signalling, illustrating the importance of nucleocytoplasmic trafficking in plant innate immunity. Indeed, spatial restriction of defence regulators by the nuclear envelope and stimulus-induced nuclear translocation constitute an important level of defence-associated gene regulation in plants. A significant number of effectors from different microbial pathogens are targeted to the plant cell nucleus. In addition, key host factors, including resistance proteins, immunity components, transcription factors and transcriptional regulators shuttle between the cytoplasm and the nucleus, and their level of nuclear accumulation determines the output of the defence response, further confirming the crucial role played by the nucleus during the interaction between plants and pathogens. Here, we discuss recent findings that situate the nucleus at the frontline of the mutual recognition between plants and invading microbes.

  3. Type II protein arginine methyltransferase 5 (PRMT5) is required for circadian period determination in Arabidopsis thaliana

    PubMed Central

    Hong, Sunghyun; Lutz, Kerry; Kerstetter, Randall A.; Michael, Todd P.; McClung, C. Robertson

    2010-01-01

    Posttranslational modification is an important element in circadian clock function from cyanobacteria through plants and mammals. For example, a number of key clock components are phosphorylated and thereby marked for subsequent ubiquitination and degradation. Through forward genetic analysis we demonstrate that protein arginine methyltransferase 5 (PRMT5; At4g31120) is a critical determinant of circadian period in Arabidopsis. PRMT5 is coregulated with a set of 1,253 genes that shows alterations in phase of expression in response to entrainment to thermocycles versus photocycles in constant temperature. PRMT5 encodes a type II protein arginine methyltransferase that catalyzes the symmetric dimethylation of arginine residues (Rsme2). Rsme2 modification has been observed in many taxa, and targets include histones, components of the transcription complex, and components of the spliceosome. Neither arginine methylation nor PRMT5 has been implicated previously in circadian clock function, but the period lengthening associated with mutational disruption of prmt5 indicates that Rsme2 is a decoration important for the Arabidopsis clock and possibly for clocks in general. PMID:21097700

  4. C3-C4 Intermediate Species in Alternanthera (Amaranthaceae) 1

    PubMed Central

    Rajendrudu, Gedupudi; Prasad, Jasty S. R.; Das, V. S. Rama

    1986-01-01

    Two naturally occurring species of the genus Alternanthera, namely A. ficoides and A. tenella, were identified as C3-C4 intermediates based on leaf anatomy, photosynthetic CO2 compensation point (Γ), O2 response of г, light intensity response of г, and the activities of key enzymes of photosynthesis. A. ficoides and A. tenella exhibited a less distinct Kranz-like leaf anatomy with substantial accumulation of starch both in mesophyll and bundle sheath cells. Photosynthetic CO2 compensation points of these two intermediate species at 29°C were much lower than in C3 plants and ranged from 18 to 22 microliters per liter. Although A. ficoides and A. tenella exhibited similar intermediacy in г, the apparent photorespiratory component of O2 inhibition in A. ficoides is lower than in A. tenella. The г progressively decreases from 35 microliters per liter at lowest light intensity to 18 microliters per liter at highest light intensity in A. tenella. It was, however, constant in A. ficoides at 20 to 25 microliters per liter between light intensities measured. The rates of net photosynthesis at 21% O2 and 29°C by A. ficoides and A. tenella were 25 to 28 milligrams CO2 per square decimeter per hour which are intermediate between values obtained for Tridax procumbens and A. pungens, C3 and C4 species, respectively. The activities of key enzymes of C4 photosynthesis, phosphoenolpyruvate carboxylase, pyruvate Pi dikinase, NAD malic enzyme, NADP malic enzyme and phosphoenolpyruvate carboxykinase in the two intermediates, A. ficoides and A. tenella are very low or insignificant. Results indicated that the relatively low apparent photorespiratory component in these two species is presumably the basis for the C3-C4 intermediate photosynthesis. Images Fig. 2 PMID:16664634

  5. Defining Health Research for Development: The perspective of stakeholders from an international health research partnership in Ghana and Tanzania.

    PubMed

    Ward, Claire Leonie; Shaw, David; Anane-Sarpong, Evelyn; Sankoh, Osman; Tanner, Marcel; Elger, Bernice

    2017-05-03

    The study uses a qualitative empirical method to define Health Research for Development. This project explores the perspectives of stakeholders in an international health research partnership operating in Ghana and Tanzania. We conducted 52 key informant interviews with major stakeholders in an international multicenter partnership between GlaxoSmithKline (GSK, Vaccine Developer) and the global health nonprofit organisation PATH and its Malaria Vaccine Initiative program (PATH/MVI, Funder-Development Partner), (RTS, S) (NCT00866619). The respondents included teams from four clinical research centres (two centres in Ghana and two in Tanzania) and various collaborating partners. This paper analyses responses to the question: What is Health Research for Development? Based on the stakeholders' experience the respondents offered many ways of defining Health Research for Development. The responses fell into four broad themes: i) Equitable Partnerships; ii) System Sustainability; iii) Addressing Local Health Targets, and iv) Regional Commitment to Benefit Sharing. Through defining Health Research for Development six key learning points were generated from the four result themes: 1) Ensure there is local research leadership working with the collaborative partnership, and local healthcare system, to align the project agenda and activities with local research and health priorities; 2) Know the country-specific context - map the social, health, legislative and political setting; 3) Define an explicit development component and plan of action in a research project; 4) Address the barriers and opportunities to sustain system capacity. 5) Support decentralised health system decision-making to facilitate the translation pathway; 6) Govern, monitor and evaluate the development components of health research partnerships. Overall, equity and unity between partners are required to deliver health research for development. © 2017 John Wiley & Sons Ltd.

  6. Identifying Patterns in Implementation of Hospital Pressure Ulcer Prevention Programs: A Multisite Qualitative Study.

    PubMed

    Soban, Lynn M; Finley, Erin P; Miltner, Rebecca S

    2016-01-01

    To describe the presence or absence of key components of hospital pressure ulcer (PU) prevention programs in 6 acute care hospitals. Multisite comparative case study. Using purposeful selection based on PU rates (high vs low) and hospital size, 6 hospitals within the Veterans Health Administration health care system were invited to participate. Key informant interviews (n = 48) were conducted in each of the 6 participating hospitals among individuals playing key roles in PU prevention: senior nursing leadership (n = 9), nurse manager (n = 7), wound care specialist (n = 6), frontline RNs (n = 26). Qualitative data were collected during face-to-face, semistructured interviews. Interview protocols were tailored to each interviewee's role with a core set of common questions covering 3 major content areas: (1) practice environment (eg, policies and wound care specialists), (2) current prevention practices (eg, conduct of PU risk assessment and skin inspection), and (3) barriers to PU prevention. We conducted structured coding of 5 key components of PU prevention programs and cross-case analysis to identify patterns in operationalization and implementation of program components across hospitals based on facility size and PU rates (low vs high). All hospitals had implemented all PU prevention program components. Component operationalization varied considerably across hospitals. Wound care specialists were integral to the operationalization of the 4 other program components examined; however, staffing levels and work assignments of wound care specialists varied widely. Patterns emerged among hospitals with low and high PU rates with respect to wound care specialist staffing, data monitoring, and staff education. We found hospital-level variations in PU prevention programs. Wound care specialist staffing may represent a potential point of leverage in achieving other PU program components, particularly performance monitoring and staff education.

  7. Low Dose Ionizing Radiation Modulates Immune Function

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

    Nelson, Gregory A.

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokinemore » secretion patterns characteristic of a “Th2 polarized” immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in the dose range of 5 to 50 cGy.« less

  8. MutSα's Multi-Domain Allosteric Response to Three DNA Damage Types Revealed by Machine Learning

    NASA Astrophysics Data System (ADS)

    Melvin, Ryan L.; Thompson, William G.; Godwin, Ryan C.; Gmeiner, William H.; Salsbury, Freddie R.

    2017-03-01

    MutSalpha is a key component in the mismatch repair (MMR) pathway. This protein is responsible for initiating the signaling pathways for DNA repair or cell death. Herein we investigate this heterodimer’s post-recognition, post-binding response to three types of DNA damage involving cytotoxic, anti-cancer agents - carboplatin, cisplatin, and FdU. Through a combination of supervised and unsupervised machine learning techniques along with more traditional structural and kinetic analysis applied to all-atom molecular dynamics (MD) calculations, we predict that MutSalpha has a distinct response to each of the three damage types. Via a binary classification tree (a supervised machine learning technique), we identify key hydrogen bond motifs unique to each type of damage and suggest residues for experimental mutation studies. Through a combination of a recently developed clustering (unsupervised learning) algorithm, RMSF calculations, PCA, and correlated motions we predict that each type of damage causes MutS↵to explore a specific region of conformation space. Detailed analysis suggests a short range effect for carboplatin - primarily altering the structures and kinetics of residues within 10 angstroms of the damaged DNA - and distinct longer-range effects for cisplatin and FdU. In our simulations, we also observe that a key phenylalanine residue - known to stack with a mismatched or unmatched bases in MMR - stacks with the base complementary to the damaged base in 88.61% of MD frames containing carboplatinated DNA. Similarly, this Phe71 stacks with the base complementary to damage in 91.73% of frames with cisplatinated DNA. This residue, however, stacks with the damaged base itself in 62.18% of trajectory frames with FdU-substituted DNA and has no stacking interaction at all in 30.72% of these frames. Each drug investigated here induces a unique perturbation in the MutS↵complex, indicating the possibility of a distinct signaling event and specific repair or death pathway (or set of pathways) for a given type of damage.

  9. Placebo Response is Driven by UCS Revaluation: Evidence, Neurophysiological Consequences and a Quantitative Model

    PubMed Central

    Puviani, Luca; Rama, Sidita

    2016-01-01

    Despite growing scientific interest in the placebo effect and increasing understanding of neurobiological mechanisms, theoretical modeling of the placebo response remains poorly developed. The most extensively accepted theories are expectation and conditioning, involving both conscious and unconscious information processing. However, it is not completely understood how these mechanisms can shape the placebo response. We focus here on neural processes which can account for key properties of the response to substance intake. It is shown that placebo response can be conceptualized as a reaction of a distributed neural system within the central nervous system. Such a reaction represents an integrated component of the response to open substance administration (or to substance intake) and is updated through “unconditioned stimulus (UCS) revaluation learning”. The analysis leads to a theorem, which proves the existence of two distinct quantities coded within the brain, these are the expected or prediction outcome and the reactive response. We show that the reactive response is updated automatically by implicit revaluation learning, while the expected outcome can also be modulated through conscious information processing. Conceptualizing the response to substance intake in terms of UCS revaluation learning leads to the theoretical formulation of a potential neuropharmacological treatment for increasing unlimitedly the effectiveness of a given drug. PMID:27436417

  10. Placebo Response is Driven by UCS Revaluation: Evidence, Neurophysiological Consequences and a Quantitative Model.

    PubMed

    Puviani, Luca; Rama, Sidita

    2016-07-20

    Despite growing scientific interest in the placebo effect and increasing understanding of neurobiological mechanisms, theoretical modeling of the placebo response remains poorly developed. The most extensively accepted theories are expectation and conditioning, involving both conscious and unconscious information processing. However, it is not completely understood how these mechanisms can shape the placebo response. We focus here on neural processes which can account for key properties of the response to substance intake. It is shown that placebo response can be conceptualized as a reaction of a distributed neural system within the central nervous system. Such a reaction represents an integrated component of the response to open substance administration (or to substance intake) and is updated through "unconditioned stimulus (UCS) revaluation learning". The analysis leads to a theorem, which proves the existence of two distinct quantities coded within the brain, these are the expected or prediction outcome and the reactive response. We show that the reactive response is updated automatically by implicit revaluation learning, while the expected outcome can also be modulated through conscious information processing. Conceptualizing the response to substance intake in terms of UCS revaluation learning leads to the theoretical formulation of a potential neuropharmacological treatment for increasing unlimitedly the effectiveness of a given drug.

  11. HUMAN RESPONDING ON RANDOM-INTERVAL SCHEDULES OF RESPONSE-COST PUNISHMENT: THE ROLE OF REDUCED REINFORCEMENT DENSITY

    PubMed Central

    Pietras, Cynthia J; Brandt, Andrew E; Searcy, Gabriel D

    2010-01-01

    An experiment with adult humans investigated the effects of response-contingent money loss (response-cost punishment) on monetary-reinforced responding. A yoked-control procedure was used to separate the effects on responding of the response-cost contingency from the effects of reduced reinforcement density. Eight adults pressed buttons for money on a three-component multiple reinforcement schedule. During baseline, responding in all components produced money gains according to a random-interval 20-s schedule. During punishment conditions, responding during the punishment component conjointly produced money losses according to a random-interval schedule. The value of the response-cost schedule was manipulated across conditions to systematically evaluate the effects on responding of response-cost frequency. Participants were assigned to one of two yoked-control conditions. For participants in the Yoked Punishment group, during punishment conditions money losses were delivered in the yoked component response independently at the same intervals that money losses were produced in the punishment component. For participants in the Yoked Reinforcement group, responding in the yoked component produced the same net earnings as produced in the punishment component. In 6 of 8 participants, contingent response cost selectively decreased response rates in the punishment component and the magnitude of the decrease was directly related to the punishment schedule value. Under punishment conditions, for participants in the Yoked Punishment group response rates in the yoked component also decreased, but the decrease was less than that observed in the punishment component, whereas for participants in the Yoked Reinforcement group response rates in the yoked component remained similar to rates in the no-punishment component. These results provide further evidence that contingent response cost functions similarly to noxious punishers in that it appears to suppress responding apart from its effects on reinforcement density. PMID:20676265

  12. A computational framework for modeling targets as complex adaptive systems

    NASA Astrophysics Data System (ADS)

    Santos, Eugene; Santos, Eunice E.; Korah, John; Murugappan, Vairavan; Subramanian, Suresh

    2017-05-01

    Modeling large military targets is a challenge as they can be complex systems encompassing myriad combinations of human, technological, and social elements that interact, leading to complex behaviors. Moreover, such targets have multiple components and structures, extending across multiple spatial and temporal scales, and are in a state of change, either in response to events in the environment or changes within the system. Complex adaptive system (CAS) theory can help in capturing the dynamism, interactions, and more importantly various emergent behaviors, displayed by the targets. However, a key stumbling block is incorporating information from various intelligence, surveillance and reconnaissance (ISR) sources, while dealing with the inherent uncertainty, incompleteness and time criticality of real world information. To overcome these challenges, we present a probabilistic reasoning network based framework called complex adaptive Bayesian Knowledge Base (caBKB). caBKB is a rigorous, overarching and axiomatic framework that models two key processes, namely information aggregation and information composition. While information aggregation deals with the union, merger and concatenation of information and takes into account issues such as source reliability and information inconsistencies, information composition focuses on combining information components where such components may have well defined operations. Since caBKBs can explicitly model the relationships between information pieces at various scales, it provides unique capabilities such as the ability to de-aggregate and de-compose information for detailed analysis. Using a scenario from the Network Centric Operations (NCO) domain, we will describe how our framework can be used for modeling targets with a focus on methodologies for quantifying NCO performance metrics.

  13. Host responses and metabolic profiles of wood components in Dutch elm hybrids with a contrasting tolerance to Dutch elm disease

    PubMed Central

    Ďurkovič, Jaroslav; Kačík, František; Olčák, Dušan; Kučerová, Veronika; Krajňáková, Jana

    2014-01-01

    Background and Aims Changes occurring in the macromolecular traits of cell wall components in elm wood following attack by Ophiostoma novo-ulmi, the causative agent of Dutch elm disease (DED), are poorly understood. The purpose of this study was to compare host responses and the metabolic profiles of wood components for two Dutch elm (Ulmus) hybrids, ‘Groeneveld’ (a susceptible clone) and ‘Dodoens’ (a tolerant clone), that have contrasting survival strategies upon infection with the current prevalent strain of DED. Methods Ten-year-old plants of the hybrid elms were inoculated with O. novo-ulmi ssp. americana × novo-ulmi. Measurements were made of the content of main cell wall components and extractives, lignin monomer composition, macromolecular traits of cellulose and neutral saccharide composition. Key Results Upon infection, medium molecular weight macromolecules of cellulose were degraded in both the susceptible and tolerant elm hybrids, resulting in the occurrence of secondary cell wall ruptures and cracks in the vessels, but rarely in the fibres. The 13C nuclear magnetic resonance spectra revealed that loss of crystalline and non-crystalline cellulose regions occurred in parallel. The rate of cellulose degradation was influenced by the syringyl:guaiacyl ratio in lignin. Both hybrids commonly responded to the medium molecular weight cellulose degradation with the biosynthesis of high molecular weight macromolecules of cellulose, resulting in a significant increase in values for the degree of polymerization and polydispersity. Other responses of the hybrids included an increase in lignin content, a decrease in relative proportions of d-glucose, and an increase in proportions of d-xylose. Differential responses between the hybrids were found in the syringyl:guaiacyl ratio in lignin. Conclusions In susceptible ‘Groeneveld’ plants, syringyl-rich lignin provided a far greater degree of protection from cellulose degradation than in ‘Dodoens’, but only guaiacyl-rich lignin in ‘Dodoens’ plants was involved in successful defence against the fungus. This finding was confirmed by the associations of vanillin and vanillic acid with the DED-tolerant ‘Dodoens’ plants in a multivariate analysis of wood traits. PMID:24854167

  14. Surfactant Protein-D Is Essential for Immunity to Helminth Infection

    PubMed Central

    Schnoeller, Corinna; Chetty, Alisha; Smith, Katherine; Darby, Matthew; Roberts, Luke; Mackay, Rosie-Marie; Whitwell, Harry J.; Timms, John F.; Madsen, Jens; Selkirk, Murray E.; Brombacher, Frank; Clark, Howard William; Horsnell, William G. C.

    2016-01-01

    Pulmonary epithelial cell responses can enhance type 2 immunity and contribute to control of nematode infections. An important epithelial product is the collectin Surfactant Protein D (SP-D). We found that SP-D concentrations increased in the lung following Nippostrongylus brasiliensis infection; this increase was dependent on key components of the type 2 immune response. We carried out loss and gain of function studies of SP-D to establish if SP-D was required for optimal immunity to the parasite. N. brasiliensis infection of SP-D-/- mice resulted in profound impairment of host innate immunity and ability to resolve infection. Raising pulmonary SP-D levels prior to infection enhanced parasite expulsion and type 2 immune responses, including increased numbers of IL-13 producing type 2 innate lymphoid cells (ILC2), elevated expression of markers of alternative activation by alveolar macrophages (alvM) and increased production of the type 2 cytokines IL-4 and IL-13. Adoptive transfer of alvM from SP-D-treated parasite infected mice into naïve recipients enhanced immunity to N. brasiliensis. Protection was associated with selective binding by the SP-D carbohydrate recognition domain (CRD) to L4 parasites to enhance their killing by alvM. These findings are the first demonstration that the collectin SP-D is an essential component of host innate immunity to helminths. PMID:26900854

  15. Enzyme-triggered compound release using functionalized antimicrobial peptide derivatives† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc04435b Click here for additional data file.

    PubMed Central

    Kashibe, Masayoshi; Matsumoto, Kengo; Hori, Yuichiro

    2017-01-01

    Controlled release is one of the key technologies for medical innovation, and many stimulus-responsive nanocarriers have been developed to utilize this technology. Enzyme activity is one of the most useful stimuli, because many enzymes are specifically activated in diseased tissues. However, controlled release stimulated by enzyme activity has not been frequently reported. One of the reasons for this is the lack of versatility of carriers. Most of the reported stimulus-responsive systems involve a sophisticated design and a complicated process for the synthesis of stimulus-responsive nanocarrier components. The purpose of this study was to develop versatile controlled release systems triggered by various stimuli, including enzyme activity, without modifying the nanocarrier components. We developed two controlled release systems, both of which comprised a liposome as the nanocarrier and a membrane-damaging peptide, temporin L (TL), and its derivatives as the release-controllers. One system utilized branched peptides for proteases, and the other utilized phosphopeptides for phosphatases. In our systems, the target enzymes converted the non-membrane-damaging TL derivatives into membrane-damaging peptides and released the liposome inclusion. We demonstrated the use of our antimicrobial peptide-based controlled release systems for different enzymes and showed the promise of this technology as a novel theranostic tool. PMID:28451373

  16. Targeting Protein Quality Control Mechanisms by Natural Products to Promote Healthy Ageing.

    PubMed

    Wedel, Sophia; Manola, Maria; Cavinato, Maria; Trougakos, Ioannis P; Jansen-Dürr, Pidder

    2018-05-19

    Organismal ageing is associated with increased chance of morbidity or mortality and it is driven by diverse molecular pathways that are affected by both environmental and genetic factors. The progression of ageing correlates with the gradual accumulation of stressors and damaged biomolecules due to the time-dependent decline of stress resistance and functional capacity, which eventually compromise cellular homeodynamics. As protein machines carry out the majority of cellular functions, proteome quality control is critical for cellular functionality and is carried out through the curating activity of the proteostasis network (PN). Key components of the PN are the two main degradation machineries, namely the ubiquitin-proteasome and autophagy-lysosome pathways along with several stress-responsive pathways, such as that of nuclear factor erythroid 2-related factor 2 (Nrf2), which mobilises cytoprotective genomic responses against oxidative and/or xenobiotic damage. Reportedly, genetic or dietary interventions that activate components of the PN delay ageing in evolutionarily diverse organisms. Natural products (extracts or pure compounds) represent an extraordinary inventory of highly diverse structural scaffolds that offer promising activities towards meeting the challenge of increasing healthspan and/or delaying ageing (e.g., spermidine, quercetin or sulforaphane). Herein, we review those natural compounds that have been found to activate proteostatic and/or anti-stress cellular responses and hence have the potential to delay cellular senescence and/or in vivo ageing.

  17. Model verification of mixed dynamic systems. [POGO problem in liquid propellant rockets

    NASA Technical Reports Server (NTRS)

    Chrostowski, J. D.; Evensen, D. A.; Hasselman, T. K.

    1978-01-01

    A parameter-estimation method is described for verifying the mathematical model of mixed (combined interactive components from various engineering fields) dynamic systems against pertinent experimental data. The model verification problem is divided into two separate parts: defining a proper model and evaluating the parameters of that model. The main idea is to use differences between measured and predicted behavior (response) to adjust automatically the key parameters of a model so as to minimize response differences. To achieve the goal of modeling flexibility, the method combines the convenience of automated matrix generation with the generality of direct matrix input. The equations of motion are treated in first-order form, allowing for nonsymmetric matrices, modeling of general networks, and complex-mode analysis. The effectiveness of the method is demonstrated for an example problem involving a complex hydraulic-mechanical system.

  18. Effective health care corporate compliance.

    PubMed

    Saum, T B; Byassee, J

    2000-01-01

    The pace and intensity of oversight and investigation of health care organizations has greatly increased at all levels. Well run organizations with ethical management committed to following all laws and regulations are still at risk for compliance violations and punitive penalties. Under the Federal Sentencing Guidelines, organizations with an "effective" corporate compliance program may receive reduced penalties. The seven components of an effective program as defined in the guidelines are: (1) Standards and procedures; (2) oversight responsibilities; (3) employee training; (4) monitoring and auditing; (5) reporting systems; (6) enforcement and discipline; and (7) response and prevention. Lack of a compliance program needlessly exposes the organization to an avoidable risk of damage from non-compliance--whether intentional or not. Moreover, an effective program can contribute to the efficient operation of the organization and be a key piece of its corporate culture.

  19. Pay attention to me! Late ERPs reveal gender differences in attention allocated to romantic partners.

    PubMed

    Burdwood, Erin N; Simons, Robert F

    2016-04-01

    The present study employed late ERPs to examine differences in the association between neural responses to romantic partners and relationship quality factors across men and women. Participants passively viewed photos of their romantic partners, celebrities, and strangers during a computerized facial processing task. All participants demonstrated enhanced positivity to partner faces at late ERP components (P3 and LPP), furthering the notion that significant others elicit more motivated and sustained attention than do other familiar or unfamiliar individuals. Neural responses to romantic partner faces were influenced by factors including overall relationship quality, investment, and communication quality, with associations varying by gender. Results highlight the key role that relationship quality factors play in the immediate processing of romantic partners-a finding with implications for couples counseling and research. © 2015 Society for Psychophysiological Research.

  20. NEDDylation promotes stress granule assembly

    PubMed Central

    Jayabalan, Aravinth Kumar; Sanchez, Anthony; Park, Ra Young; Yoon, Sang Pil; Kang, Gum-Yong; Baek, Je-Hyun; Anderson, Paul; Kee, Younghoon; Ohn, Takbum

    2016-01-01

    Stress granules (SGs) harbour translationally stalled messenger ribonucleoproteins and play important roles in regulating gene expression and cell fate. Here we show that neddylation promotes SG assembly in response to arsenite-induced oxidative stress. Inhibition or depletion of key components of the neddylation machinery concomitantly inhibits stress-induced polysome disassembly and SG assembly. Affinity purification and subsequent mass-spectrometric analysis of Nedd8-conjugated proteins from translationally stalled ribosomal fractions identified ribosomal proteins, translation factors and RNA-binding proteins (RBPs), including SRSF3, a previously known SG regulator. We show that SRSF3 is selectively neddylated at Lys85 in response to arsenite. A non-neddylatable SRSF3 (K85R) mutant do not prevent arsenite-induced polysome disassembly, but fails to support the SG assembly, suggesting that the neddylation pathway plays an important role in SG assembly. PMID:27381497

  1. HSP70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene

    PubMed Central

    He, Haiying; Chen, Changmin; Xie, Yue; Asea, Alexzander; Calderwood, Stuart K.

    2000-01-01

    Heat shock protein 70 (HSP70) is a molecular chaperone involved in protein folding and resistance to the deleterious effects of stress. Here we show that HSP70 suppresses transcription of c-fos, an early response gene that is a key component of the ubiquitous AP-1 transcription factor complex. HSP70 repressed Ras-induced c-fos transcription only in the presence of functional heat shock factor1 (HSF1). This suggests that HSP70 functions as a corepressor with HSF1 to inhibit c-fos gene transcription. Therefore, besides its known function in the stress response, HSP70 also has the property of a corepressor and combines with HSF1 to antagonize Fos expression and may thus impact multiple aspects of cell regulation. PMID:11189444

  2. Diversity in the origins of proteostasis networks- a driver for protein function in evolution

    PubMed Central

    Powers, Evan T.; Balch, William E.

    2013-01-01

    Although a protein’s primary sequence largely determines its function, proteins can adopt different folding states in response to changes in the environment, some of which may be deleterious to the organism. All organisms, including Bacteria, Archaea and Eukarya, have evolved a protein homeostasis network, or proteostasis network, that consists of chaperones and folding factors, degradation components, signalling pathways and specialized compartmentalized modules that manage protein folding in response to environmental stimuli and variation. Surveying the origins of proteostasis networks reveals that they have co-evolved with the proteome to regulate the physiological state of the cell, reflecting the unique stresses that different cells or organisms experience, and that they have a key role in driving evolution by closely managing the link between the phenotype and the genotype. PMID:23463216

  3. In-Vitro Induced Immunosuppression in a Rotary Cell Culture System

    NASA Technical Reports Server (NTRS)

    Grimm, Elizabeth A.

    1998-01-01

    The function of the innate immune system is to provide a first-line of defense against infectious organisms, via control of bacterial and viral growth using antigen nonspecific means. These nonspecific immune effectors include macrophages and Natural Killing (NK) cells, and certain cytokines elicited in response to "super antigens" on the infectious agents. This innate system usually keeps most infectious agents from rapidly growing while the adaptive immune system is generating a specific response complete with immunologic memory. Compelling evidence suggests that space flight results in various immunosuppressive effects, including reduced innate and adaptive immune responses. We were particularly concerned with reduced NK activity at landing, and have asked whether the microgravity component of space flight could be responsible for the previously observed NK defect. We have conclusively demonstrated that simulated microgravity as provided by the Synthecon bioreactors does not inhibit the NK function nor the IL-2 activation of lymphokine-activated killing (LAK). Interleukin-2 is the key cytokine responsible for activation of NK cells to express LAK, as well as to support differentiation of lymphocytes during adaptive immune responses. Therefore, we have disproved our original hypothesis based on poor NK in many of the astronauts upon landing.

  4. S-Nitrosoglutathione is a component of wound- and salicylic acid-induced systemic responses in Arabidopsis thaliana.

    PubMed

    Espunya, M Carme; De Michele, Roberto; Gómez-Cadenas, Aurelio; Martínez, M Carmen

    2012-05-01

    S-Nitrosoglutathione (GSNO) is a bioactive, stable, and mobile reservoir of nitric oxide (NO), and an important player in defence responses to herbivory and pathogen attack in plants. It has been demonstrated previously that GSNO reductase (GSNOR) is the main enzyme responsible for the in vivo control of intracellular levels of GSNO. In this study, the role of S-nitrosothiols, in particular of GSNO, in systemic defence responses in Arabidopsis thaliana was investigated further. It was shown that GSNO levels increased rapidly and uniformly in injured Arabidopsis leaves, whereas in systemic leaves GSNO was first detected in vascular tissues and later spread over the parenchyma, suggesting that GSNO is involved in the transmission of the wound mobile signal through the vascular tissue. Moreover, GSNO accumulation was required to activate the jasmonic acid (JA)-dependent wound responses, whereas the alternative JA-independent wound-signalling pathway did not involve GSNO. Furthermore, extending previous work on the role of GSNOR in pathogenesis, it was shown that GSNO acts synergistically with salicylic acid in systemic acquired resistance activation. In conclusion, GSNOR appears to be a key regulator of systemic defence responses, in both wounding and pathogenesis.

  5. Small Group Discussion as a Key Component in Online Assessment Training for Enhanced Student Learning in Web-Based Peer Assessment

    ERIC Educational Resources Information Center

    Liu, Xiongyi; Li, Lan; Zhang, Zhihong

    2018-01-01

    The purpose of this study is to examine the effect of online assessment training, with synchronous group discussion as a key component, on subsequent web-based peer assessment results. Participants included 81 college students, mostly women, taking a business writing class. After initial submission of a draft counter-offer letter, they completed…

  6. Fixed-ratio discrimination: effects of response-produced blackouts1

    PubMed Central

    Lydersen, Tore; Crossman, E. K.

    1974-01-01

    For three pigeons, reinforcement depended upon a left side-key response after execution of a fixed ratio 10 on the center key, and upon a right side-key response after fixed ratio 20. Each response during the fixed ratios produced a 0.5-sec blackout. The time between the first and last response in fixed ratio 10 was then equated with the time between the first and last response in fixed ratio 20 by increasing the blackout duration. The accuracy of side-key choice was disrupted, thereby suggesting that time, rather than number of responses, controlled choice responding. When the time between the first and last response was equated during both ratios, asymptotic accuracy was approximately equal to (two birds) or somewhat higher than (one bird) that obtained previously. The results of probes with intermediate fixed ratios and blackouts suggested that control of side-key choice had transferred from the time between the first and last response in ratios to blackout duration. PMID:16811819

  7. Probabilistic seismic hazard assessment for the effect of vertical ground motions on seismic response of highway bridges

    NASA Astrophysics Data System (ADS)

    Yilmaz, Zeynep

    Typically, the vertical component of the ground motion is not considered explicitly in seismic design of bridges, but in some cases the vertical component can have a significant effect on the structural response. The key question of when the vertical component should be incorporated in design is answered by the probabilistic seismic hazard assessment study incorporating the probabilistic seismic demand models and ground motion models. Nonlinear simulation models with varying configurations of an existing bridge in California were considered in the analytical study. The simulation models were subjected to the set of selected ground motions in two stages: at first, only horizontal components of the motion were applied; while in the second stage the structures were subjected to both horizontal and vertical components applied simultaneously and the ground motions that produced the largest adverse effects on the bridge system were identified. Moment demand in the mid-span and at the support of the longitudinal girder and the axial force demand in the column are found to be significantly affected by the vertical excitations. These response parameters can be modeled using simple ground motion parameters such as horizontal spectral acceleration and vertical spectral acceleration within 5% to 30% error margin depending on the type of the parameter and the period of the structure. For a complete hazard assessment, both of these ground motion parameters explaining the structural behavior should also be modeled. For the horizontal spectral acceleration, Abrahamson and Silva (2008) model was used within many available standard model. A new NGA vertical ground motion model consistent with the horizontal model was constructed. These models are combined in a vector probabilistic seismic hazard analyses. Series of hazard curves developed and presented for different locations in Bay Area for soil site conditions to provide a roadmap for the prediction of these features for future earthquakes. Findings from this study will contribute to the development of revised guidelines to address vertical ground motion effects, particularly in the near fault regions, in the seismic design of highway bridges.

  8. Development of a novel parallel-spool pilot operated high-pressure solenoid valve with high flow rate and high speed

    NASA Astrophysics Data System (ADS)

    Dong, Dai; Li, Xiaoning

    2015-03-01

    High-pressure solenoid valve with high flow rate and high speed is a key component in an underwater driving system. However, traditional single spool pilot operated valve cannot meet the demands of both high flow rate and high speed simultaneously. A new structure for a high pressure solenoid valve is needed to meet the demand of the underwater driving system. A novel parallel-spool pilot operated high-pressure solenoid valve is proposed to overcome the drawback of the current single spool design. Mathematical models of the opening process and flow rate of the valve are established. Opening response time of the valve is subdivided into 4 parts to analyze the properties of the opening response. Corresponding formulas to solve 4 parts of the response time are derived. Key factors that influence the opening response time are analyzed. According to the mathematical model of the valve, a simulation of the opening process is carried out by MATLAB. Parameters are chosen based on theoretical analysis to design the test prototype of the new type of valve. Opening response time of the designed valve is tested by verifying response of the current in the coil and displacement of the main valve spool. The experimental results are in agreement with the simulated results, therefore the validity of the theoretical analysis is verified. Experimental opening response time of the valve is 48.3 ms at working pressure of 10 MPa. The flow capacity test shows that the largest effective area is 126 mm2 and the largest air flow rate is 2320 L/s. According to the result of the load driving test, the valve can meet the demands of the driving system. The proposed valve with parallel spools provides a new method for the design of a high-pressure valve with fast response and large flow rate.

  9. Response inhibition or evaluation of danger? An event-related potential study regarding the origin of the motor interference effect from dangerous objects.

    PubMed

    Liu, Peng; Cao, Rong; Chen, Xuhai; Wang, Yonghui

    2017-06-01

    Previous studies have identified an interference effect from dangerous objects on prepared responses. However, its origin remains arguable. This study investigated the neural processes of this motor interference effect. The design adopted a motor priming paradigm mixed with a Go/NoGo task. Pictures of a left or right hand were used as primes, and green (Go signal) or red (NoGo signal) circles superimposed on dangerous or safe objects were used as targets. Participants were instructed to prepare the corresponding key press using the hand that was consistent with the handedness of the prime and not to execute until a Go signal appeared. Behavioral results indicated longer reaction times and a trend that participants made more errors for the dangerous condition than for the safe condition in the Go trials. However, the difference between the error rates for the dangerous and safe conditions did not emerge in the NoGo trials. Event-related potential analysis revealed a similar effect on the P3 component, which may reflect an assignment of cognitive resources to evaluate danger. More positive parietal P3 amplitudes were identified in response to the dangerous condition in the Go trials. However, the difference in the P3 amplitudes between the dangerous and safe conditions was not significant in the NoGo trials. Together, the motor interference effect from dangerous objects may originate from the danger evaluations. Furthermore, differences between the dangerous and safe conditions also emerged in the P1, posterior N1, P2, and posterior N2 components; the possible processes that underlie these components were discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Hyperosmotic nanoemulsions: Development and application of a new antimicrobial treatment for wound care

    NASA Astrophysics Data System (ADS)

    Connell, Sean

    Wound healing is the intricate process that restores function to damaged skin. The process consists of the inflammatory, proliferative and remodeling phases that orchestrate dynamic cellular responses to regenerate the cutaneous barrier. However, microbial contamination of the wound site stimulates a deleterious inflammatory response with the production of endotoxins, exotoxins and proteases that result in secondary injury. The end result is delayed healing, protracted debilitation and increased health care costs. Controlling contamination is critical for proper wound management and reduced burden on the healthcare system. Based on this concern, we developed and applied a new antimicrobial therapeutic that relies on hyperosmotic nanoemulsions (HNE). The biomechanical process consists of a high-energy nanoemulsion component that permeates the protective microbial membrane and a (ii) nonionic hyperosmoticum that facilitates intracellular water extraction to critically dehydrate the pathogen. HNE was shown to be effective against a multitude of pathogens including bacteria, antibiotic-resistant variants, fungi and viruses. Reported non-clinical studies demonstrate that the membrane disrupting nanoemulsion and hyperosmotic component act synergistically to enhance microbicidal activity. Further, results illustrate that pathogen inactivation was rapid as determined by ion and macromolecule leakage assays. Application of HNE in a pre-clinical animal model of wound healing demonstrated the treatment actively promoted healing to reduce treatment times. HNE mitigated wound infection to reduce the inflammatory response and mechanically debrided the wound to facilitate wound closure. Recent work further enhanced the stability of the nanoemulsion component with the addition of surfactant stabilizers using a low-energy spontaneous emulsification process. The refined nanoemulsion composition was stable against physical stressors and long-term storage without disrupting the intrinsic antimicrobial attributes. The reported findings have key implications for the development and application of a new antimicrobial therapeutic platform for wound management.

  11. The MAPKK FgMkk1 of Fusarium graminearum regulates vegetative differentiation, multiple stress response, and virulence via the cell wall integrity and high-osmolarity glycerol signaling pathways.

    PubMed

    Yun, Yingzi; Liu, Zunyong; Zhang, Jingze; Shim, Won-Bo; Chen, Yun; Ma, Zhonghua

    2014-07-01

    Mitogen-activated protein (MAP) kinases play crucial roles in regulating fungal development, growth and pathogenicity, and in responses to the environment. In this study, we characterized a MAP kinase kinase FgMkk1 in Fusarium graminearum, the causal agent of wheat head blight. Phenotypic analyses of the FgMKK1 mutant (ΔFgMKK1) showed that FgMkk1 is involved in the regulation of hyphal growth, pigmentation, conidiation, deoxynivalenol biosynthesis and virulence of F. graminearum. ΔFgMKK1 also showed increased sensitivity to cell wall-damaging agents, and to osmotic and oxidative stresses, but exhibited decreased sensitivity to the fungicides iprodione and fludioxonil. In addition, the mutant revealed increased sensitivity to a biocontrol agent, Trichoderma atroviride. Western blot assays revealed that FgMkk1 positively regulates phosphorylation of the MAP kinases Mgv1 and FgOs-2, the key component in the cell wall integrity (CWI) and high-osmolarity glycerol (HOG) signalling pathway respectively. Yeast two-hybrid assay indicated that Mgv1 interacts with a transcription factor FgRlm1. The FgRLM1 mutant (ΔFgRLM1) showed increased sensitivity to cell wall-damaging agents and exhibited decreased virulence. Taken together, our data indicated that FgMkk1 is an upstream component of Mgv1, and regulates vegetative differentiation, multiple stress response and virulence via the CWI and HOG signalling pathways. FgRlm1 may be a downstream component of Mgv1 in the CWI pathway in F. graminearum. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  12. funRNA: a fungi-centered genomics platform for genes encoding key components of RNAi.

    PubMed

    Choi, Jaeyoung; Kim, Ki-Tae; Jeon, Jongbum; Wu, Jiayao; Song, Hyeunjeong; Asiegbu, Fred O; Lee, Yong-Hwan

    2014-01-01

    RNA interference (RNAi) is involved in genome defense as well as diverse cellular, developmental, and physiological processes. Key components of RNAi are Argonaute, Dicer, and RNA-dependent RNA polymerase (RdRP), which have been functionally characterized mainly in model organisms. The key components are believed to exist throughout eukaryotes; however, there is no systematic platform for archiving and dissecting these important gene families. In addition, few fungi have been studied to date, limiting our understanding of RNAi in fungi. Here we present funRNA http://funrna.riceblast.snu.ac.kr/, a fungal kingdom-wide comparative genomics platform for putative genes encoding Argonaute, Dicer, and RdRP. To identify and archive genes encoding the abovementioned key components, protein domain profiles were determined from reference sequences obtained from UniProtKB/SwissProt. The domain profiles were searched using fungal, metazoan, and plant genomes, as well as bacterial and archaeal genomes. 1,163, 442, and 678 genes encoding Argonaute, Dicer, and RdRP, respectively, were predicted. Based on the identification results, active site variation of Argonaute, diversification of Dicer, and sequence analysis of RdRP were discussed in a fungus-oriented manner. funRNA provides results from diverse bioinformatics programs and job submission forms for BLAST, BLASTMatrix, and ClustalW. Furthermore, sequence collections created in funRNA are synced with several gene family analysis portals and databases, offering further analysis opportunities. funRNA provides identification results from a broad taxonomic range and diverse analysis functions, and could be used in diverse comparative and evolutionary studies. It could serve as a versatile genomics workbench for key components of RNAi.

  13. RECOVERY ACT - Thylakoid Assembly and Folded Protein Transport by the Tat Pathway

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

    Dabney-Smith, Carole

    Assembly of functional photosystems complete with necessary intrinsic (membrane-bound) and extrinsic proteins requires the function of at least 3 protein transport pathways in thylakoid membranes. Our research focuses on one of those pathways, a unique and essential protein transport pathway found in the chloroplasts of plants, bacteria, and some archaebacteria, the Twin arginine translocation (Tat) system. The chloroplast Tat (cpTat) system is thought to be responsible for the proper location of ~50% of thylakoid lumen proteins, several of which are necessary for proper photosystem assembly, maintenance, and function. Specifically, cpTat systems are unique because they transport fully folded and assembledmore » proteins across ion tight membranes using only three membrane components, Tha4, Hcf106, and cpTatC, and the protonmotive force generated by photosynthesis. Despite the importance of the cpTat system in plants, the mechanism of transport of a folded precursor is not well known. Our long-term goal is to investigate the role protein transport systems have on organelle biogenesis, particularly the assembly of membrane protein complexes in thylakoids of chloroplasts. The objective of this proposal is to correlate structural changes in the membrane-bound cpTat component, Tha4, to the mechanism of translocation of folded-precursor substrates across the membrane bilayer by using a cysteine accessibility and crosslinking approach. Our central hypothesis is that the precursor passes through a proteinaceous pore of assembled Tha4 protomers that have undergone a conformational or topological change in response to transport. This research is predicated upon the observations that Tha4 exists in molar excess in the membrane relative to the other cpTat components; its regulated assembly to the precursor-bound receptor; and our data showing oligomerization of Tha4 into very large complexes in response to transport. Our rationale for these studies is that understanding cpTat system mechanism in chloroplasts will lead to a better understanding of the biogenesis of photosynthetic membranes potentially providing a means to engineer photosynthetic complexes into synthetic membranes for energy production. We are especially well prepared to undertake this project because we have developed a novel functional replacement assay, which was used to demonstrate a correlation of Tha4 oligomerization to transport. Thylakoids of plant chloroplasts provide a very robust, reliable assay to gain mechanistic detail about cpTat systems, providing most of the biochemical analyses to date. We plan to test our central hypothesis and accomplish the overall objective of this proposal by (1) Identifying the cpTat component(s) that interact with the mature domain of precursor during transport, (2) Determining the organization of the cpTat translocon, and (3) Comparing Tha4 topology in thylakoids during active transport and at rest. The proposed studies are innovative due to our ability to correlate structural changes in cpTat protein complexes during the transport of precursor. At the completion of this project, we expect to know the cpTat component(s) that interacts directly with the mature domain of the precursor, important because it is not known which components comprise the pore for passage of the mature domain. We also expect to know the arrangement of the components in the cpTat transport complex through direct interaction between Tha4 and the other CpTat components, a key point to establishing the mechanism of translocation. Lastly, we expect to correlate topological changes of Tha4 with precursor transport, key to establishing Tha4's role in the transport process. The successful completion of these studies is expected to have an important impact in understanding chloroplast biogenesis and assembly of photosynthetic complexes in plants and photosynthetic bacteria.« less

  14. ChIP-seq reveals broad roles of SARD1 and CBP60g in regulating plant immunity.

    PubMed

    Sun, Tongjun; Zhang, Yaxi; Li, Yan; Zhang, Qian; Ding, Yuli; Zhang, Yuelin

    2015-12-18

    Recognition of pathogens by host plants leads to rapid transcriptional reprogramming and activation of defence responses. The expression of many defence regulators is induced in this process, but the mechanisms of how they are controlled transcriptionally are largely unknown. Here we use chromatin immunoprecipitation sequencing to show that the transcription factors SARD1 and CBP60g bind to the promoter regions of a large number of genes encoding key regulators of plant immunity. Among them are positive regulators of systemic immunity and signalling components for effector-triggered immunity and PAMP-triggered immunity, which is consistent with the critical roles of SARD1 and CBP60g in these processes. In addition, SARD1 and CBP60g target a number of genes encoding negative regulators of plant immunity, suggesting that they are also involved in negative feedback regulation of defence responses. Based on these findings we propose that SARD1 and CBP60g function as master regulators of plant immune responses.

  15. Dysregulation of neural calcium signaling in Alzheimer disease, bipolar disorder and schizophrenia

    PubMed Central

    Berridge, Michael J.

    2013-01-01

    Neurons have highly developed Ca2+ signaling systems responsible for regulating a large number of neural functions such as the control of brain rhythms, information processing and the changes in synaptic plasticity that underpin learning and memory. The tonic excitatory drive, which is activated by the ascending arousal system, is particularly important for processes such as sensory perception, cognition and consciousness. The Ca2+ signaling pathway is a key component of this arousal system that regulates the neuronal excitability responsible for controlling the neural brain rhythms required for information processing and cognition. Dysregulation of the Ca2+ signaling pathway responsible for many of these neuronal processes has been implicated in the development of some of the major neural diseases in man such as Alzheimer disease, bipolar disorder and schizophrenia. Various treatments, which are known to act by reducing the activity of Ca2+ signaling, have proved successful in alleviating the symptoms of some of these neural diseases. PMID:22895098

  16. The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1.

    PubMed

    Thomas, Paul G; Dash, Pradyot; Aldridge, Jerry R; Ellebedy, Ali H; Reynolds, Cory; Funk, Amy J; Martin, William J; Lamkanfi, Mohamed; Webby, Richard J; Boyd, Kelli L; Doherty, Peter C; Kanneganti, Thirumala-Devi

    2009-04-17

    Virus-induced interlukin-1beta (IL-1beta) and IL-18 production in macrophages are mediated via caspase-1 pathway. Multiple microbial components, including viral RNA, are thought to trigger assembly of the cryopyrin inflammasome resulting in caspase-1 activation. Here, we demonstrated that Nlrp3(-/-) and Casp1(-/-) mice were more susceptible than wild-type mice after infection with a pathogenic influenza A virus. This enhanced morbidity correlated with decreased neutrophil and monocyte recruitment and reduced cytokine and chemokine production. Despite the effect on innate immunity, cryopyrin-deficiency was not associated with any obvious defect in virus control or on the later emergence of the adaptive response. Early epithelial necrosis was, however, more severe in the infected mutants, with extensive collagen deposition leading to later respiratory compromise. These findings reveal a function of the cryopyrin inflammasome in healing responses. Thus, cryopyrin and caspase-1 are central to both innate immunity and to moderating lung pathology in influenza pneumonia.

  17. Operational atmospheric modeling system CARIS for effective emergency response associated with hazardous chemical releases in Korea.

    PubMed

    Kim, Cheol-Hee; Park, Jin-Ho; Park, Cheol-Jin; Na, Jin-Gyun

    2004-03-01

    The Chemical Accidents Response Information System (CARIS) was developed at the Center for Chemical Safety Management in South Korea in order to track and predict the dispersion of hazardous chemicals in the case of an accident or terrorist attack involving chemical companies. The main objective of CARIS is to facilitate an efficient emergency response to hazardous chemical accidents by rapidly providing key information in the decision-making process. In particular, the atmospheric modeling system implemented in CARIS, which is composed of a real-time numerical weather forecasting model and an air pollution dispersion model, can be used as a tool to forecast concentrations and to provide a wide range of assessments associated with various hazardous chemicals in real time. This article introduces the components of CARIS and describes its operational modeling system. Some examples of the operational modeling system and its use for emergency preparedness are presented and discussed. Finally, this article evaluates the current numerical weather prediction model for Korea.

  18. [The genetic determination and function of RR-proteins--the regulators of photoperiodic reaction and circadian rhythms in plants].

    PubMed

    Tots'kyĭ, V M; D'iachenko, L F; Muterko, O F; Balashova, I A; Toptikov, V A

    2012-01-01

    The present review devoted to the analysis of recent literature on genetic determination and the domain organization of the newly discovered two-component signaling systems in pro- and eukaryotes. These structures are involved in the regulation of numerous morphological and physiological processes in plants. RR-proteins, it the key elements of signaling systems, they launch a cascade of phosphotransferase reactions and directly or indirectly regulate the transcription and activity other proteins, including enzymes, in response to hormones or environmental factors. Modern views on the molecular and genetic mechanisms of photoperiodic response, circadian rhythms and anti-stress responses in plants are set out in these positions. The relationship between gene expression and photoreceptor sensitivity of plants to photoperiod traced. We present our own data obtained on the isogenic lines of wheat, where been showed dependence expression of structural genes of enzymes on the allelic composition of individual PRR-loci and the duration action of low temperature.

  19. Endogenous antigen processing drives the primary CD4+ T cell response to influenza

    PubMed Central

    Miller, Michael A.; Ganesan, Asha Purnima V.; Luckashenak, Nancy; Mendonca, Mark; Eisenlohr, Laurence C.

    2015-01-01

    By convention, CD4+ T lymphocytes recognize foreign and self peptides derived from internalized antigens in combination with MHC class II molecules. Alternative pathways of epitope production have been identified but their contributions to host defense have not been established. We show here in a mouse infection model that the CD4+ T cell response to influenza, critical for durable protection from the virus, is driven principally by unconventional processing of antigen synthesized within the infected antigen-presenting cell, not by classical processing of endocytosed virions or material from infected cells. Investigation of the cellular components involved, including the H2-M molecular chaperone, the proteasome, and gamma-interferon inducible lysosomal thiol reductase revealed considerable heterogeneity in the generation of individual epitopes, an arrangement that ensures peptide diversity and broad CD4+ T cell engagement. These results could fundamentally revise strategies for rational vaccine design and may lead to key insights into the induction of autoimmune and anti-tumor responses. PMID:26413780

  20. Cyclone preparedness and response: an analysis of lessons identified using an adapted military planning framework.

    PubMed

    Tatham, Peter; Oloruntoba, Richard; Spens, Karen

    2012-01-01

    The United Kingdom uses the Defence Lines of Development (DLOD) framework to analyse and understand the key components and costs of a military capability. Rooted in the Resource Based View (RBV) of a firm, an adapted DLOD approach is employed to explore, analyse and discuss the preparedness, planning and response strategies of two markedly different countries (Australia and Bangladesh) when faced with a major cyclone event of a comparable size. Given the numerous similarities in the challenges facing military forces in a complex emergency and humanitarian agencies in a natural disaster, the paper demonstrates the applicability of the DLOD framework as an analysis and planning tool in the cyclone preparedness planning and response phases, and more broadly within the disaster management area. In addition, the paper highlights the benefit to disaster managers, policymakers and researchers of exploiting comparative cross-learning opportunities from disaster events, drawn from different sectors and countries. © 2012 The Author(s). Disasters © Overseas Development Institute, 2012.

  1. Stress responses in Streptococcus species and their effects on the host.

    PubMed

    Nguyen, Cuong Thach; Park, Sang-Sang; Rhee, Dong-Kwon

    2015-11-01

    Streptococci cause a variety of diseases, such as dental caries, pharyngitis, meningitis, pneumonia, bacteremia, endocarditis, erysipelas, and necrotizing fasciitis. The natural niche of this genus of bacteria ranges from the mouth and nasopharynx to the skin, indicating that the bacteria will inevitably be subjected to environmental changes during invasion into the host, where it is exposed to the host immune system. Thus, the Streptococcus-host interaction determines whether bacteria are cleared by the host's defenses or whether they survive after invasion to cause serious diseases. If this interaction was to be deciphered, it could aid in the development of novel preventive and therapeutic agents. Streptococcus species possess many virulent factors, such as peroxidases and heat-shock proteins (HSPs), which play key roles in protecting the bacteria from hostile host environments. This review will discuss insights into the mechanism(s) by which streptococci adapt to host environments. Additionally, we will address how streptococcal infections trigger host stress responses; however, the mechanism by which bacterial components modulate host stress responses remains largely unknown.

  2. Resolving dynamics of cell signaling via real-time imaging of the immunological synapse.

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

    Stevens, Mark A.; Pfeiffer, Janet R.; Wilson, Bridget S.

    2009-10-01

    This highly interdisciplinary team has developed dual-color, total internal reflection microscopy (TIRF-M) methods that enable us to optically detect and track in real time protein migration and clustering at membrane interfaces. By coupling TIRF-M with advanced analysis techniques (image correlation spectroscopy, single particle tracking) we have captured subtle changes in membrane organization that characterize immune responses. We have used this approach to elucidate the initial stages of cell activation in the IgE signaling network of mast cells and the Toll-like receptor (TLR-4) response in macrophages stimulated by bacteria. To help interpret these measurements, we have undertaken a computational modeling effortmore » to connect the protein motion and lipid interactions. This work provides a deeper understanding of the initial stages of cellular response to external agents, including dynamics of interaction of key components in the signaling network at the 'immunological synapse,' the contact region of the cell and its adversary.« less

  3. O-Linked-N-Acetylglucosamine Cycling and Insulin Signaling Are Required for the Glucose Stress Response in Caenorhabditis elegans

    PubMed Central

    Mondoux, Michelle A.; Love, Dona C.; Ghosh, Salil K.; Fukushige, Tetsunari; Bond, Michelle; Weerasinghe, Gayani R.; Hanover, John A.; Krause, Michael W.

    2011-01-01

    In a variety of organisms, including worms, flies, and mammals, glucose homeostasis is maintained by insulin-like signaling in a robust network of opposing and complementary signaling pathways. The hexosamine signaling pathway, terminating in O-linked-N-acetylglucosamine (O-GlcNAc) cycling, is a key sensor of nutrient status and has been genetically linked to the regulation of insulin signaling in Caenorhabditis elegans. Here we demonstrate that O-GlcNAc cycling and insulin signaling are both essential components of the C. elegans response to glucose stress. A number of insulin-dependent processes were found to be sensitive to glucose stress, including fertility, reproductive timing, and dauer formation, yet each of these differed in their threshold of sensitivity to glucose excess. Our findings suggest that O-GlcNAc cycling and insulin signaling are both required for a robust and adaptable response to glucose stress, but these two pathways show complex and interdependent roles in the maintenance of glucose–insulin homeostasis. PMID:21441213

  4. Sizing Power Components of an Electrically Driven Tail Cone Thruster and a Range Extender

    NASA Technical Reports Server (NTRS)

    Jansen, Ralph H.; Bowman, Cheryl; Jankovsky, Amy

    2016-01-01

    The aeronautics industry has been challenged on many fronts to increase efficiency, reduce emissions, and decrease dependency on carbon-based fuels. This paper provides an overview of the turboelectric and hybrid electric technologies being developed under NASA's Advanced Air Transportation Technology (AATT) Project and discusses how these technologies can impact vehicle design. The discussion includes an overview of key hybrid electric studies and technology investments, the approach to making informed investment decisions based on key performance parameters and mission studies, and the power system architectures for two candidate aircraft. Finally, the power components for a single-aisle turboelectric aircraft with an electrically driven tail cone thruster and for a hybrid-electric nine-passenger aircraft with a range extender are parametrically sized, and the sensitivity of these components to key parameters is presented.

  5. Etiological classification of depression based on the enzymes of tryptophan metabolism.

    PubMed

    Fukuda, Katsuhiko

    2014-12-24

    Viewed in terms of input and output, the mechanisms of depression are still akin to a black box. However, there must be main pivots for diverse types of depression. From recent therapeutic observations, both the serotonin (5-HT) and kynurenine pathways of tryptophan metabolism may be of particular importance to improved understanding of depression. Here, I propose an etiological classification of depression, based on key peripheral and central enzymes of tryptophan metabolism. Endogenous depression is caused by a larger genetic component than reactive depression. Besides enterochromaffin and mast cells, tryptophan hydroxylase 1 (TPH1), primarily expressed in the gastrointestinal tract, is also found in 5-hydroxytryptophan-producing cells (5-HTP cells) in normal intestinal enterocytes, which are thought to essentially shunt 5-HT production in 5-HT-producing cells. Genetic studies have reported an association between TPH1 and depression, or the responsiveness of depression to antidepressive medication. Therefore, it is possible that hypofunctional 5-HTP cells (reflecting TPH1 dysfunction) in the periphery lead to deficient brain 5-HT levels. Additionally,it has been reported that higher TPH2 expression in depressed suicides may reflect a homeostatic response to deficient 5-HT levels. Subsequently, endogenous depression may be caused by TPH1 dysfunction combined with compensatory TPH2 activation. Reactive depression results from life stresses and involves the hypothalamic-pituitary-adrenal axis, with resulting cortisol production inducing tryptophan 2,3-dioxygenase (TDO) activation. In secondary depression, caused by inflammation, infection, or oxidative stress, indoleamine 2,3-dioxygenase (IDO) is activated. In both reactive and secondary depression, the balance between 3-hydroxykynurenine (3-HK) and kynurenic acid may shift towards 3-HK production via kynurenine-3-monooxygenase (KMO) activation. By shifting the equilibrium position of key enzymes of tryptophan metabolism, the classical classification of depression can be reorganized, as below. Peripheral classification of depression by key enzymes: TPH1 dysfunction, TDO activation, IDO activation. Central classification: TPH2 activation, KMO activation. Etiological classification of depression expressed by peripheral (TPH1, TDO, IDO) and central (TPH2, KMO)enzymes of tryptophan metabolism may enable depression to be viewed as a clear box, with the inner components available for inspection and treatment.

  6. Characteristics of Successful and Unsuccessful Mental Health Referrals of Refugees

    PubMed Central

    Shannon, Patricia J.; Vinson, Gregory A.; Cook, Tonya; Lennon, Evelyn

    2018-01-01

    In this community based participatory research study, we explored key characteristics of mental health referrals of refugees using stories of providers collected through an on-line survey. Ten coders sorted 60 stories of successful referrals and 34 stories of unsuccessful referrals into domains using the critical incident technique. Principal Components Analysis yielded categories of successful referrals that included: active care coordination, proactive resolution of barriers, establishment of trust, and culturally responsive care. Unsuccessful referrals were characterized by cultural barriers, lack of care coordination, language barriers, system barriers, providers being unwilling to see refugees. Recommendations for training and policy are discussed. PMID:25735618

  7. The United States Culture Collection Network (USCCN): Enhancing Microbial Genomics Research through Living Microbe Culture Collections

    DOE PAGES

    Boundy-Mills, Kyria; Hess, Matthias; Bennett, A. Rick; ...

    2015-06-19

    The mission of the United States Culture Collection Network (USCCN;http://usccn.org) is “to facilitate the safe and responsible utilization of microbial resources for research, education, industry, medicine, and agriculture for the betterment of human kind.” Microbial culture collections are a key component of life science research, biotechnology, and emerging global biobased economies. Here, representatives and users of several microbial culture collections from the United States and Europe gathered at the University of California, Davis, to discuss how collections of microorganisms can better serve users and stakeholders and to showcase existing resources available in public culture collections.

  8. Test Results of a 200 GHz, Low Noise Downconverter for USAT Applications

    NASA Technical Reports Server (NTRS)

    Fujikawa, Gene (Compiler); Svoboda, James S.

    1996-01-01

    A key component in the development of the advanced communication technology satellite (ACTS) ultra small aperture terminal (USAT) earth station is the low noise down converter (LND). NASA Lewis Research Center has tested a version of an LND designed by Electrodyne Systems Corporation. A number of tests were conducted to characterize the radio frequency performance of the LND over temperature. The test results presented in this paper are frequency response, noise figure, gain, group delay, power transfer characteristics, image rejection, and spurious product suppression. The LND was one of several critical microwave subsystems developed and tested for the ACTS USAT Earth stations.

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

    Anastasi, A.; Basti, A.; Bedeschi, F.

    We report the test of many of the key elements of the laser-based calibration system for muon g - 2 experiment E989 at Fermilab. The test was performed at the Laboratori Nazionali di Frascati's Beam Test Facility using a 450 MeV electron beam impinging on a small subset of the final g - 2 lead-fluoride crystal calorimeter system. The calibration system was configured as planned for the E989 experiment and uses the same type of laser and most of the final optical elements. We show results regarding the calorimeter's response calibration, the maximum equivalent electron energy which can be providedmore » by the laser and the stability of the calibration system components.« less

  10. Parameter Estimation for Viscoplastic Material Modeling

    NASA Technical Reports Server (NTRS)

    Saleeb, Atef F.; Gendy, Atef S.; Wilt, Thomas E.

    1997-01-01

    A key ingredient in the design of engineering components and structures under general thermomechanical loading is the use of mathematical constitutive models (e.g. in finite element analysis) capable of accurate representation of short and long term stress/deformation responses. In addition to the ever-increasing complexity of recent viscoplastic models of this type, they often also require a large number of material constants to describe a host of (anticipated) physical phenomena and complicated deformation mechanisms. In turn, the experimental characterization of these material parameters constitutes the major factor in the successful and effective utilization of any given constitutive model; i.e., the problem of constitutive parameter estimation from experimental measurements.

  11. The United States Culture Collection Network (USCCN): Enhancing Microbial Genomics Research through Living Microbe Culture Collections

    PubMed Central

    Boundy-Mills, Kyria; Hess, Matthias; Bennett, A. Rick; Ryan, Matthew; Kang, Seogchan; Nobles, David; Eisen, Jonathan A.; Inderbitzin, Patrik; Sitepu, Irnayuli R.; Torok, Tamas; Brown, Daniel R.; Cho, Juliana; Wertz, John E.; Mukherjee, Supratim; Cady, Sherry L.

    2015-01-01

    The mission of the United States Culture Collection Network (USCCN; http://usccn.org) is “to facilitate the safe and responsible utilization of microbial resources for research, education, industry, medicine, and agriculture for the betterment of human kind.” Microbial culture collections are a key component of life science research, biotechnology, and emerging global biobased economies. Representatives and users of several microbial culture collections from the United States and Europe gathered at the University of California, Davis, to discuss how collections of microorganisms can better serve users and stakeholders and to showcase existing resources available in public culture collections. PMID:26092453

  12. Test results of a 20 GHz, low noise downconverter for USAT applications

    NASA Technical Reports Server (NTRS)

    Fujikawa, Gene; Svoboda, James S.

    1995-01-01

    A key component in the development of the Advanced Communications Technology Satellite (ACTS) ultra small aperture terminal (USAT) earth station is the low noise downconverter (NLD). NASA Lewis Research Center (LeRC) has tested a version of an LND designed by Electrodyne Systems Corporation. A number of tests were conducted to characterize the radio frequency performance of the LND over temperature. The test results presented in this paper are frequency response, noise figure, gain, group delay, power transfer characteristics, image rejection, and spurious product suppression. The LND was one of several critical microwave subsystems developed and tested for the ACTS USAT earth stations.

  13. An evolution in interdisciplinary competencies to prevent and manage patient violence.

    PubMed

    Morton, Paula G

    2002-01-01

    Patient violence is a growing problem in healthcare institutions. Incidents of violence lead to injuries and increased operating costs. An innovative organizational approach to this problem is inclusion of interdisciplinary competency-based staff education and practice, as a key component of a comprehensive violence prevention program.Interdisciplinary competencies include a variety of behavioral responses, aimed at prevention, environmental, interpersonal, and physical interventions and postvention techniques for aggression and violence. Methods to maintain, monitor, document, and improve staff performance and skills are delineated. Organizational investment in such interdisciplinary competency-based education and practice evolves over time. Results include fewer incidents and injuries and enhanced interdisciplinary cooperation.

  14. The United States Culture Collection Network (USCCN): Enhancing Microbial Genomics Research through Living Microbe Culture Collections

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

    Boundy-Mills, Kyria; Hess, Matthias; Bennett, A. Rick

    The mission of the United States Culture Collection Network (USCCN;http://usccn.org) is “to facilitate the safe and responsible utilization of microbial resources for research, education, industry, medicine, and agriculture for the betterment of human kind.” Microbial culture collections are a key component of life science research, biotechnology, and emerging global biobased economies. Here, representatives and users of several microbial culture collections from the United States and Europe gathered at the University of California, Davis, to discuss how collections of microorganisms can better serve users and stakeholders and to showcase existing resources available in public culture collections.

  15. The United States Culture Collection Network (USCCN): Enhancing Microbial Genomics Research through Living Microbe Culture Collections

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

    Boundy-Mills, K.; Hess, Matthias; Bennett, A. R.

    The mission of the United States Culture Collection Network (USCCN; http://usccn.org) is "to facilitate the safe and responsible utilization of microbial resources for research, education, industry, medicine, and agriculture for the betterment of human kind." Microbial culture collections are a key component of life science research, biotechnology, and emerging global biobased economies. Representatives and users of several microbial culture collections from the United States and Europe gathered at the University of California, Davis, to discuss how collections of microorganisms can better serve users and stakeholders and to showcase existing resources available in public culture collections.

  16. 5' adenosine monophosphate-activated protein kinase, metabolism and exercise.

    PubMed

    Aschenbach, William G; Sakamoto, Kei; Goodyear, Laurie J

    2004-01-01

    The 5' adenosine monophosphate-activated protein kinase (AMPK) is a member of a metabolite-sensing protein kinase family that functions as a metabolic 'fuel gauge' in skeletal muscle. AMPK is a ubiquitous heterotrimeric protein, consisting of an alpha catalytic, and beta and gamma regulatory subunits that exist in multiple isoforms and are all required for full enzymatic activity. During exercise, AMPK becomes activated in skeletal muscle in response to changes in cellular energy status (e.g. increased adenosine monophosphate [AMP]/adenosine triphosphate [ATP] and creatine/phosphocreatine ratios) in an intensity-dependent manner, and serves to inhibit ATP-consuming pathways, and activate pathways involved in carbohydrate and fatty-acid metabolism to restore ATP levels. Recent evidence shows that although AMPK plays this key metabolic role during acute bouts of exercise, it is also an important component of the adaptive response of skeletal muscles to endurance exercise training because of its ability to alter muscle fuel reserves and expression of several exercise-responsive genes. This review discusses the putative roles of AMPK in acute and chronic exercise responses, and suggests avenues for future AMPK research in exercise physiology and biochemistry.

  17. Probabilistic Structural Analysis Methods (PSAM) for select space propulsion system structural components

    NASA Technical Reports Server (NTRS)

    Cruse, T. A.

    1987-01-01

    The objective is the development of several modular structural analysis packages capable of predicting the probabilistic response distribution for key structural variables such as maximum stress, natural frequencies, transient response, etc. The structural analysis packages are to include stochastic modeling of loads, material properties, geometry (tolerances), and boundary conditions. The solution is to be in terms of the cumulative probability of exceedance distribution (CDF) and confidence bounds. Two methods of probability modeling are to be included as well as three types of structural models - probabilistic finite-element method (PFEM); probabilistic approximate analysis methods (PAAM); and probabilistic boundary element methods (PBEM). The purpose in doing probabilistic structural analysis is to provide the designer with a more realistic ability to assess the importance of uncertainty in the response of a high performance structure. Probabilistic Structural Analysis Method (PSAM) tools will estimate structural safety and reliability, while providing the engineer with information on the confidence that should be given to the predicted behavior. Perhaps most critically, the PSAM results will directly provide information on the sensitivity of the design response to those variables which are seen to be uncertain.

  18. Probabilistic Structural Analysis Methods for select space propulsion system structural components (PSAM)

    NASA Technical Reports Server (NTRS)

    Cruse, T. A.; Burnside, O. H.; Wu, Y.-T.; Polch, E. Z.; Dias, J. B.

    1988-01-01

    The objective is the development of several modular structural analysis packages capable of predicting the probabilistic response distribution for key structural variables such as maximum stress, natural frequencies, transient response, etc. The structural analysis packages are to include stochastic modeling of loads, material properties, geometry (tolerances), and boundary conditions. The solution is to be in terms of the cumulative probability of exceedance distribution (CDF) and confidence bounds. Two methods of probability modeling are to be included as well as three types of structural models - probabilistic finite-element method (PFEM); probabilistic approximate analysis methods (PAAM); and probabilistic boundary element methods (PBEM). The purpose in doing probabilistic structural analysis is to provide the designer with a more realistic ability to assess the importance of uncertainty in the response of a high performance structure. Probabilistic Structural Analysis Method (PSAM) tools will estimate structural safety and reliability, while providing the engineer with information on the confidence that should be given to the predicted behavior. Perhaps most critically, the PSAM results will directly provide information on the sensitivity of the design response to those variables which are seen to be uncertain.

  19. Unique human immune signature of Ebola virus disease in Guinea.

    PubMed

    Ruibal, Paula; Oestereich, Lisa; Lüdtke, Anja; Becker-Ziaja, Beate; Wozniak, David M; Kerber, Romy; Korva, Miša; Cabeza-Cabrerizo, Mar; Bore, Joseph A; Koundouno, Fara Raymond; Duraffour, Sophie; Weller, Romy; Thorenz, Anja; Cimini, Eleonora; Viola, Domenico; Agrati, Chiara; Repits, Johanna; Afrough, Babak; Cowley, Lauren A; Ngabo, Didier; Hinzmann, Julia; Mertens, Marc; Vitoriano, Inês; Logue, Christopher H; Boettcher, Jan Peter; Pallasch, Elisa; Sachse, Andreas; Bah, Amadou; Nitzsche, Katja; Kuisma, Eeva; Michel, Janine; Holm, Tobias; Zekeng, Elsa-Gayle; García-Dorival, Isabel; Wölfel, Roman; Stoecker, Kilian; Fleischmann, Erna; Strecker, Thomas; Di Caro, Antonino; Avšič-Županc, Tatjana; Kurth, Andreas; Meschi, Silvia; Mély, Stephane; Newman, Edmund; Bocquin, Anne; Kis, Zoltan; Kelterbaum, Anne; Molkenthin, Peter; Carletti, Fabrizio; Portmann, Jasmine; Wolff, Svenja; Castilletti, Concetta; Schudt, Gordian; Fizet, Alexandra; Ottowell, Lisa J; Herker, Eva; Jacobs, Thomas; Kretschmer, Birte; Severi, Ettore; Ouedraogo, Nobila; Lago, Mar; Negredo, Anabel; Franco, Leticia; Anda, Pedro; Schmiedel, Stefan; Kreuels, Benno; Wichmann, Dominic; Addo, Marylyn M; Lohse, Ansgar W; De Clerck, Hilde; Nanclares, Carolina; Jonckheere, Sylvie; Van Herp, Michel; Sprecher, Armand; Xiaojiang, Gao; Carrington, Mary; Miranda, Osvaldo; Castro, Carlos M; Gabriel, Martin; Drury, Patrick; Formenty, Pierre; Diallo, Boubacar; Koivogui, Lamine; Magassouba, N'Faly; Carroll, Miles W; Günther, Stephan; Muñoz-Fontela, César

    2016-05-05

    Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.

  20. An effective means for damage detection of bridges using the contact-point response of a moving test vehicle

    NASA Astrophysics Data System (ADS)

    Zhang, Bin; Qian, Yao; Wu, Yuntian; Yang, Y. B.

    2018-04-01

    To further the technique of indirect measurement, the contact-point response of a moving test vehicle is adopted for the damage detection of bridges. First, the contact-point response of the vehicle moving over the bridge is derived both analytically and in central difference form (for field use). Then, the instantaneous amplitude squared (IAS) of the driving component of the contact-point response is calculated by the Hilbert transform, making use of its narrow-band feature. The IAS peaks serve as the key parameter for damage detection. In the numerical simulation, a damage (crack) is modeled by a hinge-spring unit. The feasibility of the proposed method to detect the location and severity of a damage or multi damages of the bridge is verified. Also, the effects of surface roughness, vehicle speed, measurement noise and random traffic are studied. In the presence of ongoing traffic, the damages of the bridge are identified from the repeated or invariant IAS peaks generated for different traffic flows by the same test vehicle over the bridge.

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