WorldWideScience

Sample records for prevention p2 technologies

  1. Towards P2P XML Database Technology

    NARCIS (Netherlands)

    Y. Zhang (Ying)

    2007-01-01

    textabstractTo ease the development of data-intensive P2P applications, we envision a P2P XML Database Management System (P2P XDBMS) that acts as a database middle-ware, providing a uniform database abstraction on top of a dynamic set of distributed data sources. In this PhD work, we research which

  2. Microglia P2Y13 Receptors Prevent Astrocyte Proliferation Mediated by P2Y1 Receptors

    Directory of Open Access Journals (Sweden)

    Clara Quintas

    2018-05-01

    Full Text Available Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication. In previous studies, primary cultures of astrocytes and co-cultures of astrocytes and microglia were used to investigate the influence of microglia on astroglial proliferation induced by ADPβS, a stable ADP analog. In astrocyte cultures, ADPβS increased cell proliferation through activation of P2Y1 and P2Y12 receptors, an effect abolished in co-cultures (of astrocytes with ∼12.5% microglia. The possibility that the loss of the ADPβS-mediated effect could have been caused by a microglia-induced degradation of ADPβS or by a preferential microglial localization of P2Y1 or P2Y12 receptors was excluded. Since ADPβS also activates P2Y13 receptors, the contribution of microglial P2Y13 receptors to prevent the proliferative effect of ADPβS in co-cultures was investigated. The results obtained indicate that P2Y13 receptors are low expressed in astrocytes and mainly expressed in microglia. Furthermore, in co-cultures, ADPβS induced astroglial proliferation in the presence of the selective P2Y13 antagonist MRS 2211 (3 μM and of the selective P2Y12 antagonist AR-C66096 (0.1 μM, suggesting that activation of microglial P2Y12 and P2Y13 receptors may induce the release of messengers that inhibit astroglial proliferation mediated by P2Y1,12 receptors. In this microglia-astrocyte paracrine communication, P2Y12 receptors exert opposite effects in astroglial proliferation as a result of its cellular localization: cooperating in astrocytes with P2Y1 receptors to directly stimulate proliferation and in

  3. Pollution Prevention Successes Database (P2SDb) user guide

    International Nuclear Information System (INIS)

    1995-07-01

    When Pollution Prevention Opportunity Assessments (P2OAs) were launched at the Hanford Site during the summer of 1994, the first comment received from those using them expressed the desire for a method to report assessments electronically. As a temporary measure, macros were developed for use on word processing systems, but a more formal database was obviously needed. Additionally, increased DOE and Washington state reporting requirements for pollution prevention suggested that a database system would streamline the reporting process. The Pollution Prevention Group of Westinghouse Hanford Company (WHC) contracted with the Data Automation Engineering Department from ICF Kaiser Hanford Company (ICFKH) to develop the system. The scope was to develop a database that will track P2OAs conducted by the facilities and contractors at the Hanford Site. It will also track pollution prevention accomplishments that are not the result of P2OAs and document a portion of the Process Waste Assessments conducted in the past. To accommodate the above criteria, yet complete the system in a timely manner, the Pollution Prevention Successes Database (P2SDb) is being implemented in three phases. The first phase will automate the worksheets to provide both input and output of the data associated with the worksheets. The second phase will automate standard summary reports and ad hoc reports. The third phase will provide automated searching of the database to facilitate the sharing of pollution prevention experiences among various users. This User's Guide addresses only the Phase 1 system

  4. Pollution Prevention Successes Database (P2SDb) user guide

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-07-01

    When Pollution Prevention Opportunity Assessments (P2OAs) were launched at the Hanford Site during the summer of 1994, the first comment received from those using them expressed the desire for a method to report assessments electronically. As a temporary measure, macros were developed for use on word processing systems, but a more formal database was obviously needed. Additionally, increased DOE and Washington state reporting requirements for pollution prevention suggested that a database system would streamline the reporting process. The Pollution Prevention Group of Westinghouse Hanford Company (WHC) contracted with the Data Automation Engineering Department from ICF Kaiser Hanford Company (ICFKH) to develop the system. The scope was to develop a database that will track P2OAs conducted by the facilities and contractors at the Hanford Site. It will also track pollution prevention accomplishments that are not the result of P2OAs and document a portion of the Process Waste Assessments conducted in the past. To accommodate the above criteria, yet complete the system in a timely manner, the Pollution Prevention Successes Database (P2SDb) is being implemented in three phases. The first phase will automate the worksheets to provide both input and output of the data associated with the worksheets. The second phase will automate standard summary reports and ad hoc reports. The third phase will provide automated searching of the database to facilitate the sharing of pollution prevention experiences among various users. This User`s Guide addresses only the Phase 1 system.

  5. P2X4 receptors (P2X4Rs represent a novel target for the development of drugs to prevent and/or treat alcohol use disorders

    Directory of Open Access Journals (Sweden)

    Kelle M. Franklin

    2014-06-01

    Full Text Available Alcohol use disorders (AUDs have a staggering socioeconomic impact. Few therapeutic options are available, and they are largely inadequate. These shortcomings highlight the urgent need to develop effective medications to prevent and/or treat AUDs. A critical barrier is the lack of information regarding the molecular target(s by which ethanol (EtOH exerts its pharmacological activity. This review highlights findings implicating P2X4 receptors (P2X4Rs as a target for the development of therapeutics to treat AUDs and discusses the use of ivermectin (IVM as a potential clinical tool for treatment of AUDs. P2XRs are a family of ligand-gated ion channels activated by extracellular ATP. Of the P2XR subtypes, P2X4Rs are expressed the most abundantly in the CNS. Converging evidence suggests that P2X4Rs are involved in the development and progression of AUDs. First, in vitro studies report that pharmacologically relevant EtOH concentrations can negatively modulate ATP-activated currents. Second, P2X4Rs in the mesocorticolimbic dopamine system are thought to play a role in synaptic plasticity and are located ideally to modulate brain reward systems. Third, alcohol-preferring (P rats have lower functional expression of the p2rx4 gene than alcohol-non-preferring (NP rats suggesting an inverse relationship between alcohol intake and P2X4R expression. Similarly, whole brain p2rx4 expression has been shown to relate inversely to innate 24 hr alcohol preference across 28 strains of rats. Fourth, mice lacking the p2rx4 gene drink more EtOH than wildtype controls. Fifth, IVM, a positive modulator of P2X4Rs, antagonizes EtOH-mediated inhibition of P2X4Rs in vitro and reduces EtOH intake and preference in vivo. These findings suggest that P2X4Rs contribute to EtOH intake. The present review summarizes recent findings focusing on the P2X4R as a molecular target of EtOH action, its role in EtOH drinking behavior and modulation of its activity by IVM as a potential

  6. The "P2P" Educational Model Providing Innovative Learning by Linking Technology, Business and Research

    Science.gov (United States)

    Dickinson, Paul Gordon

    2017-01-01

    This paper evaluates the effect and potential of a new educational learning model called Peer to Peer (P2P). The study was focused on Laurea, Hyvinkaa's Finland campus and its response to bridging the gap between traditional educational methods and working reality, where modern technology plays an important role. The study describes and evaluates…

  7. Making The Decision: Pollution Prevention (P2) Equipment Evaluation, Procurement, Implementation and Monitoring

    National Research Council Canada - National Science Library

    Smith, Timothy C

    1998-01-01

    .... What is your primary objective? Is it waste reduction or saving money? Are you planning to select the best P2 options for achieving your waste reduction goals, or are you limited to selecting those options that show significant cost savings...

  8. P2X7R antagonism after subfailure overstretch injury of blood vessels reverses vasomotor dysfunction and prevents apoptosis.

    Science.gov (United States)

    Luo, Weifeng; Feldman, Daniel; McCallister, Reid; Brophy, Colleen; Cheung-Flynn, Joyce

    2017-12-01

    Human saphenous vein (HSV) is harvested and prepared prior to implantation as an arterial bypass graft. Injury and the response to injury from surgical harvest and preparation trigger cascades of molecular events and contribute to graft remodeling and intimal hyperplasia. Apoptosis is an early response after implantation that contributes the development of neointimal lesions. Here, we showed that surgical harvest and preparation of HSV leads to vasomotor dysfunction, increased apoptosis and downregulation of the phosphorylation of the anti-apoptotic protein, Niban. A model of subfailure overstretch injury in rat aorta (RA) was used to demonstrate impaired vasomotor function, increased extracellular ATP (eATP) release, and increased apoptosis following pathological vascular injury. The subfailure overstretch injury was associated with activation of p38 MAPK stress pathway and decreases in the phosphorylation of the anti-apoptotic protein Niban. Treatment of RA after overstretch injury with antagonists to purinergic P2X7 receptor (P2X7R) antagonists or P2X7R/pannexin (PanX1) complex, but not PanX1 alone, restored vasomotor function. Inhibitors to P2X7R and PanX1 reduced stretch-induced eATP release. P2X7R/PanX1 antagonism led to decrease in p38 MAPK phosphorylation, restoration of Niban phosphorylation and increases in the phosphorylation of the anti-apoptotic protein Akt in RA and reduced TNFα-stimulated caspase 3/7 activity in cultured rat vascular smooth muscle cells. In conclusion, inhibition of P2X7R after overstretch injury restored vasomotor function and inhibited apoptosis. Treatment with P2X7R/PanX1 complex inhibitors after harvest and preparation injury of blood vessels used for bypass conduits may prevent the subsequent response to injury that lead to apoptosis and represents a novel therapeutic approach to prevent graft failure.

  9. JXTA: A Technology Facilitating Mobile P2P Health Management System

    OpenAIRE

    Rajkumar, Rajasekaran; Iyengar, Nallani Chackravatula Sriman Naraya

    2012-01-01

    Objectives Mobile JXTA (Juxtapose) gaining momentum and has attracted the interest of doctors and patients through P2P service that transmits messages. Audio and video can also be transmitted through JXTA. The use of mobile streaming mechanism with the support of mobile hospital management and healthcare system would enable better interaction between doctors, nurses, and the hospital. Experimental results demonstrate good performance in comparison with conventional systems. This study evaluat...

  10. Pollution Prevention Program: Technology summary

    International Nuclear Information System (INIS)

    1994-02-01

    The Department of Energy (DOE) has established a national Research, Development, Demonstration, Testing, and Evaluation (RDDT ampersand E) Program for pollution prevention and waste minimization at its production plants During FY89/90 the Office of Environmental Restoration and Waste Management (EM), through the Office of Technology Development (OTD), established comprehensive, pollution prevention technical support programs to demonstrate new, environmentally-conscious technology for production processes. The RDDT ampersand E program now entails collaborative efforts across DOE. The Pollution Prevention Program is currently supporting three major activities: The DOE/US Air Force Memorandum of Understanding Program is a collaborative effort to utilize the combined resources of DOE and the Department of Defense, eliminate duplication of effort in developing technologies, and to facilitate technology solutions aimed at reducing waste through process modification, material substitution or recycling. The Waste Component Recycle, Treatment and Disposal Integrated Demonstration (WeDID) will develop recycle, treatment, and disposal processes and associated technologies for use in the dismantlement of non-nuclear weapons components, to support US arms treaties and policies. This program will focus on meeting all security and regulatory requirements (with additional benefit to the commercial electronics industry). The Environmentally Conscious Manufacturing Integrated Demonstration (ECMID) will effectively implement ECM technologies that address both the needs of the DOE Complex and US electronics industry, and encourage strong interaction between DOE and US industry. The ECMID will also develop life cycle analysis tools that will aid decisionmakers in selecting the optimum process based on the tradeoffs between cost an environmental impact

  11. New technology for accident prevention

    Energy Technology Data Exchange (ETDEWEB)

    Byne, P. [Shiftwork Solutions, Vancouver, BC (Canada)

    2006-07-01

    This power point presentation examined the effects of fatigue in the workplace and presented 3 technologies designed to prevent or monitor fatigue. The relationship between mental fatigue, circadian rhythms and cognitive performance was explored. Details of vigilance related degradations in the workplace were presented, as well as data on fatigue-related accidents and a time-line of meter-reading errors. It was noted that the direct cause of the Exxon Valdez disaster was sleep deprivation. Fatigue related accidents during the Gulf War were reviewed. The effects of fatigue on workplace performance include impaired logical reasoning and decision-making; impaired vigilance and attention; slowed mental operations; loss of situational awareness; slowed reaction time; and short cuts and lapses in optional or self-paced behaviours. New technologies to prevent fatigue-related accidents include (1) the driver fatigue monitor, an infra-red camera and computer that tracks a driver's slow eye-lid closures to prevent fatigue related accidents; (2) a fatigue avoidance scheduling tool (FAST) which collects actigraphs of sleep activity; and (3) SAFTE, a sleep, activity, fatigue and effectiveness model. refs., tabs., figs.

  12. Major weapon system environmental life-cycle cost estimating for Conservation, Cleanup, Compliance and Pollution Prevention (C3P2)

    Science.gov (United States)

    Hammond, Wesley; Thurston, Marland; Hood, Christopher

    1995-01-01

    The Titan 4 Space Launch Vehicle Program is one of many major weapon system programs that have modified acquisition plans and operational procedures to meet new, stringent environmental rules and regulations. The Environmental Protection Agency (EPA) and the Department of Defense (DOD) mandate to reduce the use of ozone depleting chemicals (ODC's) is just one of the regulatory changes that has affected the program. In the last few years, public environmental awareness, coupled with stricter environmental regulations, has created the need for DOD to produce environmental life-cycle cost estimates (ELCCE) for every major weapon system acquisition program. The environmental impact of the weapon system must be assessed and budgeted, considering all costs, from cradle to grave. The Office of the Secretary of Defense (OSD) has proposed that organizations consider Conservation, Cleanup, Compliance and Pollution Prevention (C(sup 3)P(sup 2)) issues associated with each acquisition program to assess life-cycle impacts and costs. The Air Force selected the Titan 4 system as the pilot program for estimating life-cycle environmental costs. The estimating task required participants to develop an ELCCE methodology, collect data to test the methodology and produce a credible cost estimate within the DOD C(sup 3)P(sup 2) definition. The estimating methodology included using the Program Office weapon system description and work breakdown structure together with operational site and manufacturing plant visits to identify environmental cost drivers. The results of the Titan IV ELCCE process are discussed and expanded to demonstrate how they can be applied to satisfy any life-cycle environmental cost estimating requirement.

  13. Oral administration of Lactococcus lactis-expressing heat shock protein 65 and tandemly repeated IA2P2 prevents type 1 diabetes in NOD mice.

    Science.gov (United States)

    Liu, Kun-Feng; Liu, Xiao-Rui; Li, Guo-Liang; Lu, Shi-Ping; Jin, Liang; Wu, Jie

    2016-06-01

    Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of insulin-secreting β cells upon autoreactive T cell attack. Oral administration of autoantigens is an attractive approach to treating T1DM, but an effective carrier should be used in order to protect antigens. Lactococcus lactis, a safe engineering strain, was used for this task in the present study. Two recombinant L. lactis expressing protein HSP65-6IA2P2 were used and be investigated the effects and mechanisms against T1DM in NOD mice. Our findings demonstrate that recombinant L. lactis strains can successfully both deliver antigens to intestinal mucosa and maintain the epitopes for a long time in NOD mice. Oral administration of recombinant L. lactis could prevent hyperglycemia, improve glucose tolerance, and reduce insulitis by inhibiting antigen-specific proliferation of T cells, augmenting regulatory immune reactions, and balancing ratios of Th17/Tregs and Th1/Th2. These results prove that orally administrated L. lactis expressing HSP65-6IA2P2 is an effective approach for the prevention of T1DM in NOD mice. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  14. GaN-Based High-k Praseodymium Oxide Gate MISFETs with P2S5/(NH42SX + UV Interface Treatment Technology

    Directory of Open Access Journals (Sweden)

    Chao-Wei Lin

    2012-01-01

    Full Text Available This study examines the praseodymium-oxide- (Pr2O3- passivated AlGaN/GaN metal-insulator-semiconductor high electron mobility transistors (MIS-HEMTs with high dielectric constant in which the AlGaN Schottky layers are treated with P2S5/(NH42SX + ultraviolet (UV illumination. An electron-beam evaporated Pr2O3 insulator is used instead of traditional plasma-assisted chemical vapor deposition (PECVD, in order to prevent plasma-induced damage to the AlGaN. In this work, the HEMTs are pretreated with P2S5/(NH42SX solution and UV illumination before the gate insulator (Pr2O3 is deposited. Since stable sulfur that is bound to the Ga species can be obtained easily and surface oxygen atoms are reduced by the P2S5/(NH42SX pretreatment, the lowest leakage current is observed in MIS-HEMT. Additionally, a low flicker noise and a low surface roughness (0.38 nm are also obtained using this novel process, which demonstrates its ability to reduce the surface states. Low gate leakage current Pr2O3 and high-k AlGaN/GaN MIS-HEMTs, with P2S5/(NH42SX + UV illumination treatment, are suited to low-noise applications, because of the electron-beam-evaporated insulator and the new chemical pretreatment.

  15. Development of Pollution Prevention Technologies

    Energy Technology Data Exchange (ETDEWEB)

    Polle, Juergen [Brooklyn College, The City University of New York (CUNY), Brooklyn, New York, (United States); Sanchez-Delgado, Roberto [Brooklyn College, The City University of New York (CUNY), Brooklyn, New York, (United States)

    2013-12-30

    This project investigated technologies that may reduce environmental pollution. This was a basic research/educational project addressing two major areas: A. In the algae research project, newly isolated strains of microalgae were investigated for feedstock production to address the production of renewable fuels. An existing collection of microalgae was screened for lipid composition to determine strains with superior composition of biofuel molecules. As many microalgae store triacylglycerides in so-called oil bodies, selected candidate strains identified from the first screen that accumulate oil bodies were selected for further biochemical analysis, because almost nothing was known about the biochemistry of these oil bodies. Understanding sequestration of triacylglycerides in intracellular storage compartments is essential to developing better strains for achieving high oil productivities by microalgae. At the onset of the project there was almost no information available on how to obtain detailed profiles of lipids from strains of microalgae. Our research developed analytical methods to determine the lipid profiles of novel microalgal strains. The project was embedded into other ongoing microalgal projects in the Polle laboratory. The project benefited the public, because students were trained in cell cultivation and in the operation of state-of-the-art analytical equipment. In addition, students at Brooklyn College were introduced into the concept of a systems biology approach to study algal biofuels production. B. A series of new nanostructured catalysts were synthesized, and characterized by a variety of physical and chemical methods. Our catalyst design leads to active nanostructures comprising small metal particles in intimate contact with strongly basic sites provided by the supports, which include poly(4-vinylpyridine), magnesium oxide, functionalized multi-walled carbon nanotubes, and graphene oxide. The new materials display a good potential as catalysts

  16. Multipurpose prevention technologies: products in development.

    Science.gov (United States)

    Friend, David R; Clark, Justin T; Kiser, Patrick F; Clark, Meredith R

    2013-12-01

    Multipurpose prevention technologies (MPTs) are broadly defined as products capable of simultaneously addressing multiple sexual and reproductive health needs including unintended pregnancy, STIs including HIV-1, and other reproductive tract infections. MPTs have been discussed for a few decades but little product development has occurred. With the recent proof-of-concept that a topically applied antiretroviral (ARV) can effectively reduce sexual transmission of HIV-1 (tenofovir 1% gel) the impetus to develop MPTs is gaining momentum. Products currently in development are broadly categorized as either long-acting or on-demand. Long-acting MPTs include intravaginal rings (IVRs) and long-acting injectable products. Several IVR MPTs are under development including one designed to release tenofovir to prevent transmission of HIV-1 and levonorgestrel (LNG) to prevent unintended pregnancy over a 90-day period. Another MPT IVR under development is designed to release the ARV dapivirine and LNG for 2 months. Long-acting injectable pre-exposure prophylaxis (PrEP) formulations of rilpivirine (TMC278) and GSK1265744 have entered clinical evaluation and could form the basis of long-acting injectable products for HIV-1 prevention and prevention of unintended pregnancy. On-demand products include TFV 1% gel (HIV-1/HSV-2 prevention), a zinc/carrageenan zinc gel (HIV-1/HSV-2 prevention), and the SILCS diaphragm administered with TFV 1% gel. Significant technical, funding, and regulatory hurdles must be overcome to develop most MPTs; however, the significant reproductive health benefits to many women around the world should provide motivation to overcome these hurdles. This article is based on a presentation at the "Product Development Workshop 2013: HIV and Multipurpose Prevention Technologies", held in Arlington, Virginia on February 21-22, 2013. It forms part of a special supplement to Antiviral Research. Copyright © 2013. Published by Elsevier B.V.

  17. The use of technology in Suicide Prevention.

    Science.gov (United States)

    Larsen, Mark E; Cummins, Nicholas; Boonstra, Tjeerd W; O'Dea, Bridianne; Tighe, Joe; Nicholas, Jennifer; Shand, Fiona; Epps, Julien; Christensen, Helen

    2015-01-01

    Suicide is one of the leading causes of death globally, and is notably a significant cause of death amongst young people. A suicide outcome is a complex combination of personal, social, and health factors, and therefore suicide prevention is a challenge, requiring a systems approach incorporating public health strategies, screening at-risk individuals, targeted interventions, and follow-up for suicide survivors and those bereaved by suicide. Engineering practice has been implicated in the hindrance of the adoption of suicide prevention strategies, such as installing safety barriers at the Golden Gate Bridge, however technological developments offer new opportunities in suicide prevention, and the potential to reduce the number of deaths by suicide. We present an overview of current technological developments which are facilitating research in the field of suicide prevention, including multiple modes of screening such as network analysis of mobile-phone collected connectivity data, automatic detection of suicidality from social media content, and crisis detection from acoustic variability in speech patterns. The current field of mhealth apps for suicide prevention is assessed, and an innovative app for an Indigenous population is presented. From this overview, future challenges - technical and ethical - are discussed.

  18. Beyond HIV microbicides: multipurpose prevention technology products.

    Science.gov (United States)

    Malcolm, R K; Boyd, P; McCoy, C F; Murphy, D J

    2014-10-01

    Multipurpose prevention technologies (MPTs) that aim to simultaneously prevent unintended pregnancy, HIV-1 infection and other sexually transmitted infections are among the most innovative and complex products currently in development within women's sexual and reproductive health care. In this review article, MPTs are placed within the wider context of combination products, combination drug products and multi-indication products. The current MPT product landscape is mapped and assessed with reference to existing products for the corresponding single indications, before identifying the gaps in the current MPT product pipeline and highlighting priority products and challenges moving forward. © 2014 Royal College of Obstetricians and Gynaecologists.

  19. P2X receptors

    OpenAIRE

    North, R. Alan

    2016-01-01

    Extracellular adenosine 5′-triphosphate (ATP) activates cell surface P2X and P2Y receptors. P2X receptors are membrane ion channels preferably permeable to sodium, potassium and calcium that open within milliseconds of the binding of ATP. In molecular architecture, they form a unique structural family. The receptor is a trimer, the binding of ATP between subunits causes them to flex together within the ectodomain and separate in the membrane-spanning region so as to open a central channel. P2...

  20. P2X7R Blockade Prevents NLRP3 Inflammasome Activation and Pancreatic Fibrosis in a Mouse Model of Chronic Pancreatitis.

    Science.gov (United States)

    Zhang, Gui-Xian; Wang, Man-Xue; Nie, Wei; Liu, Da-Wei; Zhang, Yi; Liu, Hong-Bin

    The aim of this study was to investigate the role of P2X7R (purinergic 2X7 receptor) and NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome activation in the process of pancreatic fibrosis in a mouse model of chronic pancreatitis (CP). Chronic pancreatitis was induced by repeated intraperitoneal injections of 50 μg/kg cerulein for 6 weeks in mice. P2X7R antagonist oxidized ATP (OxATP) or brilliant blue G (BBG) was administered after the last cerulein injection for 2 weeks. Pancreatic chronic inflammation and fibrosis were evaluated by histological score, Sirius red staining, and alpha-smooth muscle actin immunohistochemical staining. We further determined pancreatic P2X7R, NLRP3, and caspase-1 expressions in gene and protein levels and the pancreatic concentrations of caspase-1, interleukin 1β (IL-1β), and IL-18. The pancreatic P2X7R, NLRP3, and caspase-1 expressions in gene and protein levels and the pancreatic concentrations of caspase-1, IL-1β, and IL-18 were all reduced significantly in both the OxATP and BBG groups (P P2X7R antagonist OxATP and BBG significantly decreased pancreatic chronic inflammation and fibrosis in a mouse CP model and suggested that blockade of P2X7R-NLRP3 inflammasome signaling pathway may represent a novel therapeutic strategy for CP and its fibrotic process.

  1. P2X receptors.

    Science.gov (United States)

    North, R Alan

    2016-08-05

    Extracellular adenosine 5'-triphosphate (ATP) activates cell surface P2X and P2Y receptors. P2X receptors are membrane ion channels preferably permeable to sodium, potassium and calcium that open within milliseconds of the binding of ATP. In molecular architecture, they form a unique structural family. The receptor is a trimer, the binding of ATP between subunits causes them to flex together within the ectodomain and separate in the membrane-spanning region so as to open a central channel. P2X receptors have a widespread tissue distribution. On some smooth muscle cells, P2X receptors mediate the fast excitatory junction potential that leads to depolarization and contraction. In the central nervous system, activation of P2X receptors allows calcium to enter neurons and this can evoke slower neuromodulatory responses such as the trafficking of receptors for the neurotransmitter glutamate. In primary afferent nerves, P2X receptors are critical for the initiation of action potentials when they respond to ATP released from sensory cells such as taste buds, chemoreceptors or urothelium. In immune cells, activation of P2X receptors triggers the release of pro-inflammatory cytokines such as interleukin 1β. The development of selective blockers of different P2X receptors has led to clinical trials of their effectiveness in the management of cough, pain, inflammation and certain neurodegenerative diseases.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. © 2016 The Author(s).

  2. P2X7R blockade prevents NLRP3 inflammasome activation and brain injury in a rat model of intracerebral hemorrhage: involvement of peroxynitrite.

    Science.gov (United States)

    Feng, Liang; Chen, Yizhao; Ding, Rui; Fu, Zhenghao; Yang, Shuo; Deng, Xinqing; Zeng, Jun

    2015-10-17

    The NLR family, pyrin domain-containing 3 (NLRP3) inflammasome plays a key role in intracerebral hemorrhage (ICH)-induced inflammatory injury, and the purinergic 2X7 receptor (P2X7R) is upstream of NLRP3 activation. This study aimed to investigate how P2X7R functions in ICH-induced inflammatory injury and how the receptor interacts with the NLRP3 inflammasome. Rats were treated with P2X7R small interfering RNA (siRNA) 24 h before undergoing collagenase-induced ICH. A selective P2X7R inhibitor (blue brilliant G, BBG) or a peroxynitrite (ONOO(-)) decomposition catalyst (5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron(III) [FeTPPS]) was injected 30 min after ICH. Brain water content, hemorrhagic lesion volume, and neurological deficits were evaluated, and western blot, immunofluorescence, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were carried out. Striatal P2X7R and NLRP3 inflammasomes were activated after ICH. Gene silencing of P2X7R suppressed NLRP3 inflammasome activation and interleukin (IL)-1β/IL-18 release and significantly ameliorated brain edema and neurological deficits. Additionally, enhanced NADPH oxidase 2 (NOX2, gp91(phox)) and inducible nitric oxide synthase (iNOS), as well as their cytotoxic product (ONOO(-)) were markedly attenuated by BBG treatment following ICH. This was accompanied by downregulations of the inflammasome components, IL-1β/IL-18 and myeloperoxidase (MPO, a neutrophil marker). Most importantly, inflammasome activation and IL-1β/IL-18 release were significantly inhibited by ONOO(-) decomposition with FeTPPS. Our findings implicate that P2X7R exacerbated inflammatory progression and brain damage in ICH rats possibly via NLRP3 inflammasome-dependent IL-1β/IL-18 release and neutrophil infiltration. ONOO(-), a potential downstream signaling molecule of P2X7R, may play a critical role in triggering NLRP3 inflammasome activation.

  3. EVALUATING POLLUTION PREVENTION PROGRESS (P2P) III: AN ENVIRONMENTAL TOOL FOR SCREENING IN PRODUCT LIFE CYCLE ASSESSMENT AND CHEMICAL PROCESS DESIGN

    Science.gov (United States)

    P2P is a computer-based tool that supports the comparison of process and product alternatives in terms of environmental impacts. This tool provides screening-level information for use in process design and in product LCA. Twenty one impact categories and data for approximately ...

  4. Saperi P2P

    Directory of Open Access Journals (Sweden)

    Salvatore Iaconesi

    2009-10-01

    Full Text Available Il paper presenta l'architettura filosofica e logica di un progetto ongoing per la creazione di un'infrastruttura peer to peer per la diffusione dei saperi. Tale infrastruttura p2p vuole essere la base per costruire un framework aperto e orizzontale, che ospiti pratiche innovative di creazione, condivisione e disseminazione di informazioni e conoscenza.

  5. The study of technological prevention method of road accident ...

    African Journals Online (AJOL)

    The study of technological prevention method of road accident related to driver and vehicle. ... road accident prevention method based on the factors studied. The study of this paper can provide forceful data analysis support for the road traffic safety related research. Keywords: road accident; accident prevention; road safety.

  6. A Systematic Literature Review of Technologies for Suicidal Behavior Prevention.

    Science.gov (United States)

    Franco-Martín, Manuel A; Muñoz-Sánchez, Juan Luis; Sainz-de-Abajo, Beatriz; Castillo-Sánchez, Gema; Hamrioui, Sofiane; de la Torre-Díez, Isabel

    2018-03-05

    Suicide is the second cause of death in young people. The use of technologies as tools facilitates the detection of individuals at risk of suicide thus allowing early intervention and efficacy. Suicide can be prevented in many cases. Technology can help people at risk of suicide and their families. It could prevent situations of risk of suicide with the technological evolution that is increasing. This work is a systematic review of research papers published in the last ten years on technology for suicide prevention. In September 2017, the consultation was carried out in the scientific databases PubMed, ScienceDirect, PsycINFO, The Cochrane Library and Google Scholar. A general search was conducted with the terms "prevention" AND "suicide" AND "technology. More specific searches included technologies such as "Web", "mobile", "social networks", and others terms related to technologies. The number of articles found following the methodology proposed was 90, but only 30 are focused on the objective of this work. Most of them were Web technologies (51.61%), mobile solutions (22.58%), social networks (12.90%), machine learning (3.23%) and other technologies (9.68%). According to the results obtained, although there are technological solutions that help the prevention of suicide, much remains to be done in this field. Collaboration among technologists, psychiatrists, patients, and family members is key to advancing the development of new technology-based solutions that can help save lives.

  7. Development of laser preventive maintenance technology and application for PWRs

    International Nuclear Information System (INIS)

    Yoda, M.; Saeki, R.; Kato, H.; Chida, I.

    2008-01-01

    We developed a laser peening technology to prevent the stress corrosion cracking (SCC) on nuclear reactor in-core components. Since 2004, we started to apply it to PWRs and have practiced it three times successfully for Ikata-1,2 of Shikoku Electric Power Company as the SCC preventive maintenance technology for Alloy 600 materials. It is expected the laser peening technology will be applied to many other plants. (author)

  8. The use of technology in suicide prevention

    NARCIS (Netherlands)

    Boonstra, T.W.; Larsen, M.E.; Cummins, N.; O'Dea, B.; Tighe, J.; Nicholas, J.; Shand, F.; Epps, J.; Christensen, H.

    2015-01-01

    Suicide is one of the leading causes of death globally, and is notably a significant cause of death amongst young people. A suicide outcome is a complex combination of personal, social, and health factors, and therefore suicide prevention is a challenge, requiring a systems approach incorporating

  9. New Technology and the Prevention of Violence and Conflict

    Directory of Open Access Journals (Sweden)

    Francesco Mancini

    2013-10-01

    Full Text Available Amid unprecedented growth in access to information communication technologies (ICTs, particularly in the developing world, how can international actors, governments, and civil society organizations leverage ICTs and the data they generate to more effectively prevent violence and conflict? New research shows that there is huge potential for innovative technologies to inform conflict prevention efforts, particularly when technology is used to help information flow horizontally between citizens and when it is integrated into existing civil society initiatives.1 However, new technologies are not a panacea for preventing and reducing violence and conflict. In fact, failure to consider the possible knock-on effects of applying a specific technology can lead to fatal outcomes in violent settings. In addition, employing new technologies for conflict prevention can produce very different results depending on the context in which they are applied and whether or not those using the technology take that context into account. This is particularly true in light of the dramatic changes underway in the landscapes of violence and conflict on a global level. As such, instead of focusing on supply-driven technical fixes, those undertaking prevention initiatives should let the context inform what kind of technology is needed and what kind of approach will work best.

  10. The Use of Technology to Advance HIV Prevention for Couples.

    Science.gov (United States)

    Mitchell, Jason W

    2015-12-01

    The majority of HIV prevention studies and programs have targeted individuals or operated at the community level. This has also been the standard approach when incorporating technology (e.g., web-based, smartphones) to help improve HIV prevention efforts. The tides have turned for both approaches: greater attention is now focusing on couple-based HIV prevention and using technology to help improve these efforts for maximizing reach and potential impact. To assess the extent that technology has been used to help advance HIV prevention with couples, a literature review was conducted using four databases and included studies that collected data from 2000 to early 2015. Results from this review suggest that technology has primarily been used to help advance HIV prevention with couples as a tool for (1) recruitment and data collection and (2) intervention development. Challenges and limitations of conducting research (e.g., validity of dyadic data) along with future directions for how technology (e.g., mHealth, wearable sensors) can be used to advance HIV prevention with couples are then discussed. Given the growing and near ubiquitous use of the Internet and smartphones, further efforts in the realm of mHealth (e.g., applications or "apps") and eHealth are needed to develop novel couple-focused HIV-preventive interventions.

  11. Suicide Prevention in the Dot Com Era: Technological Aspects of a University Suicide Prevention Program

    Science.gov (United States)

    Manning, Jessica; VanDeusen, Karen

    2011-01-01

    Western Michigan University's Suicide Prevention Program utilizes multiple technological components, including an online training course, a Web site, and 2 social networking Web site profiles, as integral aspects of a comprehensive program. This article discusses the development, maintenance, use, and impact of the technological aspects of this…

  12. Preventing marine accidents caused by technology-induced human error

    OpenAIRE

    Bielić, Toni; Hasanspahić, Nermin; Čulin, Jelena

    2017-01-01

    The objective of embedding technology on board ships, to improve safety, is not fully accomplished. The paper studies marine accidents caused by human error resulting from improper human-technology interaction. The aim of the paper is to propose measures to prevent reoccurrence of such accidents. This study analyses the marine accident reports issued by Marine Accidents Investigation Branch covering the period from 2012 to 2014. The factors that caused these accidents are examined and categor...

  13. Multipurpose prevention technologies: the future of HIV and STI protection.

    Science.gov (United States)

    Fernández-Romero, José A; Deal, Carolyn; Herold, Betsy C; Schiller, John; Patton, Dorothy; Zydowsky, Thomas; Romano, Joe; Petro, Christopher D; Narasimhan, Manjulaa

    2015-07-01

    Every day, more than 1 million people are newly infected with sexually transmitted infections (STIs) that can lead to morbidity, mortality, and an increased risk of human immunodeficiency virus (HIV) acquisition. Existing prevention and management strategies, including behavior change, condom promotion, and therapy have not reduced the global incidence and prevalence, pointing to the need for novel innovative strategies. This review summarizes important issues raised during a satellite session at the first HIV Research for Prevention (R4P) conference, held in Cape Town, on October 31, 2014. We explore key STIs that are challenging public health today, new biomedical prevention approaches including multipurpose prevention technologies (MPTs), and the scientific and regulatory hurdles that must be overcome to make combination prevention tools a reality. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Transcriptional targeting of sphingosine-1- phosphate receptor S1P2 by epigallocatechin- 3-gallate prevents sphingosine-1-phosphate- mediated signaling in macrophage-differentiated HL-60 promyelomonocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Chokor R

    2014-05-01

    Full Text Available Rima Chokor, Sylvie Lamy, Borhane AnnabiLaboratoire d'Oncologie Moléculaire, Centre de recherche BIOMED, Département de Chimie, Université du Québec à Montréal, Montreal, QC, CanadaBackground: Macrophage chemotaxis followed by blood–brain barrier transendothelial migration is believed to be associated with inflammation in the central nervous system. Antineuroinflammatory strategies have identified the dietary-derived epigallocatechin-3-gallate (EGCG as an efficient agent to prevent neuroinflammation-associated neurodegenerative diseases by targeting proinflammatory mediator signaling.Methods: Given that high levels of sphingosine kinase and its product, sphingosine-1-phosphate (S1P, are present in brain tumors, we used quantitative reverse-transcription polymerase chain reaction (qRT-PCR and immunoblotting to test whether EGCG may impact on S1P receptor gene expression and prevent S1P response in undifferentiated and in terminally differentiated macrophages.Results: Promyelomonocytic human leukemia (HL-60 cells were differentiated into macrophages, and S1P triggered phosphorylation in extracellular signal-regulated kinase (ERK, c-Jun N-terminal kinase (JNK, and P38 mitogen-activated protein kinase (MAPK intracellular signaling, as shown by Western blot analysis. Pretreatment of cells with EGCG prior to differentiation inhibited the response to S1P in all three pathways, while EGCG abrogated P38 MAPK phosphorylation when present only during differentiation. Terminally-differentiated macrophages were, however, insensitive to EGCG treatment. Using qRT-PCR, gene expression of the S1P receptors S1P1, S1P2, and S1P5 was predominantly induced in terminally-differentiated macrophages, while the S1P2 was decreased by EGCG treatment.Conclusion: Our data suggest that diet-derived EGCG achieves efficient effects as a preventive agent, targeting signaling pathways prior to cell terminal differentiation. Such properties could impact on cell chemotaxis

  15. [Can gene technology in agriculture prevent hunger in the world?].

    Science.gov (United States)

    Goewie, E A

    2002-03-01

    The world population grows rapidly: the number of mouths to feed increases. Is an agriculture without gene technology able to produce sufficiently in order to prevent hunger? Research indicates that hunger is not the result of short comings in agricultural outputs. It is however the result of poverty. This problem will not be solved by gene technology based agricultural production. This article explains the basic principles of mainstream and organic farming. Literature shows that the production potentials of both kinds of farming are, by far most, not yet exhausted. Gene technology is therefore unnecessary.

  16. Technologies for HIV prevention and care: challenges for health services.

    Science.gov (United States)

    Maksud, Ivia; Fernandes, Nilo Martinez; Filgueiras, Sandra Lucia

    2015-09-01

    This article aims to consider some relevant challenges to the provision of "new prevention technologies" in health services in a scenario where the "advances" in the global response to AIDS control are visible. We take as material for analysis the information currently available on the HIV post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP), treatment as prevention (TASP) and over the counter. The methodology consisted of the survey and analysis of the Biblioteca Virtual em Saúde (BVS: MEDLINE, LILACS, WHOLIS, PAHO, SciELO) articles that addressed the issue of HIV prevention and care in the context of so-called new prevention technologies. The results of the studies show that there is assistance on the ground of clinics for the treatment of disease responses, but there are several challenges related to the sphere of prevention. The articles list some challenges regarding to management, organization of services and the attention given by health professionals to users. The current context shows evidence of the effectiveness of antiretroviral therapy in reducing the risk of HIV transmission, but the challenges for the provision of preventive technologies in health services permeate health professionals and users in their individual dimensions and health services in organizational and structural dimension. Interventions should be made available in a context of community mobilization; there should be no pressure on people to make HIV testing, antiretroviral treatment or for prevention. In the management is responsible for the training of health professionals to inform, clarify and make available to users, partners and family information about the new antiretroviral use strategies.

  17. Multipurpose prevention technologies: the future of HIV and STI protection

    Science.gov (United States)

    2015-01-01

    Every day, more than 1 million people are newly infected with sexually transmitted infections (STIs) that can lead to morbidity, mortality, and an increased risk of human immunodeficiency virus (HIV) acquisition. Existing prevention and management strategies, including behavior change, condom promotion, and therapy have not reduced the global incidence and prevalence, pointing to the need for novel innovative strategies. This review summarizes important issues raised during a satellite session at the first HIV R4P conference, held in Cape Town, on October 31, 2014. We explore key STIs that are challenging public health today; new biomedical prevention approaches including multipurpose prevention technologies (MPTs); and the scientific and regulatory hurdles that must be overcome to make combination prevention tools a reality. PMID:25759332

  18. New Technology Tools: Using Social Media for Alcohol, Drug Abuse, and Violence Prevention. Prevention Update

    Science.gov (United States)

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2011

    2011-01-01

    When it comes to using social media technology for alcohol, drug abuse, and violence prevention, Thomas Workman, at Baylor College of Medicine's John M. Eisenberg Center for Clinical Decisions and Communications Science, points out that social media is interactive. This means that a person is entering a conversation rather than a declaration, and…

  19. New horizon for infection prevention technology and implantable device

    Directory of Open Access Journals (Sweden)

    Yusuke Kondo, MD, PhD

    2016-08-01

    Full Text Available There has been a significant increase in the number of patients receiving cardiovascular implantable electronic devices (CIED over the last two decades. CIED infection represents a serious complication after CIED implantation and is associated with significant morbidity and mortality. Recently, newly advanced technologies have offered attractive and suitable therapeutic alternatives. Notably, the leadless pacemaker and anti-bacterial envelope decrease the potential risk of CIED infection and the resulting mortality, when it does occur. A completely subcutaneous implantable cardioverter defibrillator is also an alternative to the transvenous implantable cardioverter defibrillator (ICD, as it does not require implantation of any transvenous or epicardial leads. Among the patients who require ICD removal and subsequent antibiotics secondary to infection, the wearable cardioverter defibrillator represents an alternative approach to inpatient monitoring for the prevention of sudden cardiac death. In this review paper, we aimed to introduce the advanced technologies and devices for prevention of CIED infection.

  20. Assessment of pollution prevention and control technology for plating operations

    Science.gov (United States)

    Chalmer, Paul D.; Sonntag, William A.; Cushnie, George C., Jr.

    1995-01-01

    The National Center for Manufacturing Sciences (NCMS) is sponsoring an on-going project to assess pollution prevention and control technology available to the plating industry and to make this information available to those who can benefit from it. Completed project activities include extensive surveys of the plating industry and vendors of technologies and an indepth literature review. The plating industry survey was performed in cooperation with the National Association of Metal Finishers. The contractor that conducted the surveys and prepared the project products was CAI Engineering. The initial products of the project were made available in April, 1994. These products include an extensive report that presents the results of the surveys and literature review and an electronic database. The project results are useful for all those associated with pollution prevention and control in the plating industry. The results show which treatment, recovery and bath maintenance technologies have been most successful for different plating processes and the costs for purchasing and operating these technologies. The project results also cover trends in chemical substitution, the identification of compliance-problem pollutants, sludge generation rates, off-site sludge recovery and disposal options, and many other pertinent topics.

  1. A Review of Technology-Assisted Interventions for Diabetes Prevention.

    Science.gov (United States)

    Grock, Shira; Ku, Jeong-Hee; Kim, Julie; Moin, Tannaz

    2017-09-23

    The high prevalence of prediabetes and success of the diabetes prevention program (DPP) has led to increasing efforts to provide readily accessible, cost-effective DPP interventions to the general public. Technology-assisted DPP interventions are of particular interest since they may be easier to widely distribute and sustain as compared to traditional in-person DPP. The purpose of this article is to provide an overview of currently available technology-assisted DPP interventions. This review focuses on studies that have examined the use of mobile phone text messaging, smartphone/web-based apps, and telehealth programs to help prevent or delay the onset of incident type 2 diabetes. While there is variability in the results of studies focused on technology-assisted DPP and weight loss interventions, there is evidence to suggest that these programs have been associated with clinically meaningful weight loss and can be cost-effective. Patients who are at risk for diabetes can be offered technology-assisted DPP and weight loss interventions to lower their risk of incident diabetes. Further research should determine what specific combination of intervention features would be most successful.

  2. Social Media and Mobile Technology for Cancer Prevention and Treatment

    Science.gov (United States)

    Prochaska, Judith J.; Coughlin, Steven S.; Lyons, Elizabeth J.

    2018-01-01

    OVERVIEW Given the number of lives affected by cancer and the great potential for optimizing well-being via lifestyle changes, patients, providers, health care systems, advocacy groups, and entrepreneurs are looking to digital solutions to enhance patient care and broaden prevention efforts. Thousands of health-oriented mobile websites and apps have been developed, with a majority focused upon lifestyle behaviors (e.g., exercise, diet, smoking). In this review, we consider the use and potential of social media and mHealth technologies for cancer prevention, cancer treatment, and survivorship. We identify key principles in research and practice, summarize prior reviews, and highlight notable case studies and patient resources. Further, with the potential for scaled delivery and broad reach, we consider application of social media and mHealth technologies in low-resource settings. With clear advantages for reach, social media and mHealth technologies offer the ability to scale and engage entire populations at low cost, develop supportive social networks, connect patients and providers, encourage adherence with cancer care, and collect vast quantities of data for advancing cancer research. Development efforts have been rapid and numerous, yet evaluation of intervention effects on behavior change and health outcomes are sorely needed, and regulation around data security issues is notably lacking. Attention to broader audiences is also needed, with targeted development for culturally diverse groups and non-English speakers. Further investment in research to build the evidence base and identify best practices will help delineate and actualize the potential of social media and mHealth technologies for cancer prevention and treatment. PMID:28561647

  3. Social Media and Mobile Technology for Cancer Prevention and Treatment.

    Science.gov (United States)

    Prochaska, Judith J; Coughlin, Steven S; Lyons, Elizabeth J

    2017-01-01

    Given the number of lives affected by cancer and the great potential for optimizing well-being via lifestyle changes, patients, providers, health care systems, advocacy groups, and entrepreneurs are looking to digital solutions to enhance patient care and broaden prevention efforts. Thousands of health-oriented mobile websites and apps have been developed, with a majority focused upon lifestyle behaviors (e.g., exercise, diet, smoking). In this review, we consider the use and potential of social media and mHealth technologies for cancer prevention, cancer treatment, and survivorship. We identify key principles in research and practice, summarize prior reviews, and highlight notable case studies and patient resources. Further, with the potential for scaled delivery and broad reach, we consider application of social media and mHealth technologies in low-resource settings. With clear advantages for reach, social media and mHealth technologies offer the ability to scale and engage entire populations at low cost, develop supportive social networks, connect patients and providers, encourage adherence with cancer care, and collect vast quantities of data for advancing cancer research. Development efforts have been rapid and numerous, yet evaluation of intervention effects on behavior change and health outcomes are sorely needed, and regulation around data security issues is notably lacking. Attention to broader audiences is also needed, with targeted development for culturally diverse groups and non-English speakers. Further investment in research to build the evidence base and identify best practices will help delineate and actualize the potential of social media and mHealth technologies for cancer prevention and treatment.

  4. Using Technology and Assessment to Personalize Instruction: Preventing Reading Problems.

    Science.gov (United States)

    Connor, Carol McDonald

    2017-09-15

    Children who fail to learn to read proficiently are at serious risk of referral to special education, grade retention, dropping out of high school, and entering the juvenile justice system. Accumulating research suggests that instruction regimes that rely on assessment to inform instruction are effective in improving the implementation of personalized instruction and, in turn, student learning. However, teachers find it difficult to interpret assessment results in a way that optimizes learning opportunities for all of the students in their classrooms. This article focuses on the use of language, decoding, and comprehension assessments to develop personalized plans of literacy instruction for students from kindergarten through third grade, and A2i technology designed to support teachers' use of assessment to guide instruction. Results of seven randomized controlled trials demonstrate that personalized literacy instruction is more effective than traditional instruction, and that sustained implementation of personalized literacy instruction first through third grade may prevent the development of serious reading problems. We found effect sizes from .2 to .4 per school year, which translates into about a 2-month advantage. These effects accumulated from first through third grade with a large effect size (d = .7) equivalent to a full grade-equivalent advantage on standardize tests of literacy. These results demonstrate the efficacy of technology-supported personalized data-driven literacy instruction to prevent serious reading difficulties. Implications for translational prevention research in education and healthcare are discussed.

  5. Airlie House Pollution Prevention Technology Transfer pilot projects

    Energy Technology Data Exchange (ETDEWEB)

    Thuot, J.R.; Myron, H.; Gatrone, R.; McHenry, J.

    1996-08-01

    The projects were a series of pilot projects developed for DOE with the intention of transferring pollution prevention technology to private industry. The concept was to develop small technology transfer initiatives in partnership with the private sector. Argonne National Laboratory developed three projects: the microscale chemistry in education program, the microscale cost benefit study, and the Bethel New Life recycling trainee program. The two microscale chemistry projects focused on introducing microscale chemistry technologies to secondary and college education. These programs were inexpensive to develop and received excellent evaluations from participants and regulators. The recycle trainee project provided training for two participants and identified recycling and source reduction opportunities in Argonne`s solid waste stream. The pilot projects demonstrated that technology transfer initiatives can be developed and implemented with a small budget and within a short period of time. The essential components of the pilot projects were identification of target technologies that were already available, identification of target audiences, and a focus of effort to achieve a limited but defined objective.

  6. Improved Technology To Prevent Nuclear Proliferation And Counter Nuclear Terrorism

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, J; Yuldashev, B; Labov, S; Knapp, R

    2006-06-12

    As the world moves into the 21st century, the possibility of greater reliance on nuclear energy will impose additional technical requirements to prevent proliferation. In addition to proliferation resistant reactors, a careful examination of the various possible fuel cycles from cradle to grave will provide additional technical and nonproliferation challenges in the areas of conversion, enrichment, transportation, recycling and waste disposal. Radiation detection technology and information management have a prominent role in any future global regime for nonproliferation. As nuclear energy and hence nuclear materials become an increasingly global phenomenon, using local technologies and capabilities facilitate incorporation of enhanced monitoring and detection on the regional level. Radiation detection technologies are an important tool in the prevention of proliferation and countering radiological/nuclear terrorism. A variety of new developments have enabled enhanced performance in terms of energy resolution, spatial resolution, passive detection, predictive modeling and simulation, active interrogation, and ease of operation and deployment in the field. For example, various gamma ray imaging approaches are being explored to combine spatial resolution with background suppression in order to enhance sensitivity many-fold at reasonable standoff distances and acquisition times. New materials and approaches are being developed in order to provide adequate energy resolution in field use without the necessity for liquid nitrogen. Different detection algorithms enable fissile materials to be distinguished from other radioisotopes.

  7. Computer technologies for industrial risk prevention and emergency management

    International Nuclear Information System (INIS)

    Balduccelli, C.; Bologna, S.; Di Costanzo, G.; Vicoli, G.

    1996-07-01

    This document provides an overview about problems related to the engineering of computer based systems for industrial risk prevention and emergency management. Such systems are rather complex and subject to precise reliability and safety requirements. With the evolution of informatic technologies, such systems are becoming to be the means for building protective barriers for reduction of risk associated with plant operations. For giving more generality to this document, and for not concentrating on only a specific plant, the emergency management systems will be dealt with more details than ones for accident prevention. The document is organized in six chapters. Chapter one is an introduction to the problem and to its state of art, with particular emphasis to the aspects of safety requirements definition. Chapter two is an introduction to the problems related to the emergency management and to the training of operators in charge of this task. Chapter three deals in details the topic of the Training Support Systems, in particular about MUSTER (multi-user system for training and evaluation of environmental emergency response) system. Chapter four deals in details the topic of decision support systems, in particular about ISEM (information technology support for emergency management) system. Chapter five illustrates an application of support to the operators of Civil Protection Department for the management of emergencies in the fields of industrial chemical. Chapter six is about a synthesis of the state of art and the future possibilities, identifying some research and development activities more promising for the future

  8. Semisymmetric cubic graphs of order 16p2 16p2 16p2

    Indian Academy of Sciences (India)

    Abstract. An undirected graph without isolated vertices is said to be semisymmetric if its full automorphism group acts transitively on its edge set but not on its vertex set. In this paper, we inquire the existence of connected semisymmetric cubic graphs of order. 16p2. It is shown that for every odd prime p, there exists a ...

  9. An update on multipurpose prevention technologies for the prevention of HIV transmission and pregnancy.

    Science.gov (United States)

    Friend, David R

    2016-01-01

    Multipurpose Prevention Technologies (MPTs) are designed to address two or more indications from a single product. The overall goal is to prevent unintended pregnancy and transmission of one or more STIs including HIV-1. The topics covered herein are advances in over the past three years. Advances include development of novel intravaginal rings capable of releasing microbicides to prevent transmission of HIV-1 and unintended pregnancy. These rings include the potential to prevent transmission of more than one STI and unintended pregnancy. There are also gels that can potentially accomplish the same thing. Finally, combination of a drug and barrier device are also covered. There has been considerable advance in this field over the past three years. There is one ring currently in a Phase I clinical trial and others are soon to follow. Some of these drug delivery systems are by necessity rather complicated and hence could be prohibitively expensive in the developing world. Conducting multiple clinical trials to support regulatory approval of two or more indications represents a significant barrier. It remains unclear that women will be more motivated to use MPT products than has been observed in recent microbicide-only clinical trials. Despite these challenges, the need for MPTs remain acute hopefully ensuring they will continue to be developed over the coming years.

  10. New technologies in predicting, preventing and controlling emerging infectious diseases.

    Science.gov (United States)

    Christaki, Eirini

    2015-01-01

    Surveillance of emerging infectious diseases is vital for the early identification of public health threats. Emergence of novel infections is linked to human factors such as population density, travel and trade and ecological factors like climate change and agricultural practices. A wealth of new technologies is becoming increasingly available for the rapid molecular identification of pathogens but also for the more accurate monitoring of infectious disease activity. Web-based surveillance tools and epidemic intelligence methods, used by all major public health institutions, are intended to facilitate risk assessment and timely outbreak detection. In this review, we present new methods for regional and global infectious disease surveillance and advances in epidemic modeling aimed to predict and prevent future infectious diseases threats.

  11. DEVELOPMENT OF TECHNOLOGICAL SOLUTIONS FOR THE BEVERAGE INDUSTRY PREVENTIVE ORIENTATION

    Directory of Open Access Journals (Sweden)

    N. V. Nepovinnykh

    2014-01-01

    Full Text Available Summary. Market demand for foods with low fat content has been expanding, but for low-fat foods good organoleptic properties need new food ingredients and solutions. Food hydrocolloids, polysaccharides and milk proteins, now are widely used in various industries, including the dairy industry, performing various functions: to thicken aqueous solutions, foaming and stabilizing foams and others. We studied the functional and technological properties and developed technology of new types of oxygencontaining beverages (smoothies on the basis of cheese whey, natural fruit and berry juices and purees and dietary fibres «Citri-Fi», including non-starch polysaccharides (guar gum and xanthan gum, contributing to the formation of a specific texture and drink as stabilizers oxygen foam. When creating new kinds of smoothies performed construction flavored beverage profile, the definition of rational parameters of preparation and entering dietary fibres; selection of the optimal concentration of dietary fiber for the formation of the desired consistency (texture drink; study of quality and safety of new types of drinks and justification expiration dates. Based on the studies found that the use as stabilizers structure oxygen smoothie dietary fibres «Citri-Fi» in concentrations of 0.8 – 1 % and non-starch polysaccharides at concentrations of 0.1 - 0.3 % contributes to the production of foams drinks with a sufficiently high magnification. Increasing the dose of dietary fibres in making smoothies viscosity increases and weighting system, drink bad whipped, there is separation of the product into phases, the system becomes thermodynamically unstable. Production technology and recipes for new types of smoothies with dietary fibres. Preventive orientation developed oxygenated drinks allows to include them in the diet of patients with chronic heart failure, which is confirmed by appropriate investigations.

  12. Single administration of p2TA (AB103, a CD28 antagonist peptide, prevents inflammatory and thrombotic reactions and protects against gastrointestinal injury in total-body irradiated mice.

    Directory of Open Access Journals (Sweden)

    Salida Mirzoeva

    Full Text Available The goal of this study was to elucidate the action of the CD28 mimetic peptide p2TA (AB103 that attenuates an excessive inflammatory response in mitigating radiation-induced inflammatory injuries. BALB/c and A/J mice were divided into four groups: Control (C, Peptide (P; 5 mg/kg of p2TA peptide, Radiation (R; total body irradiation with 8 Gy γ-rays, and Radiation + Peptide (RP; irradiation followed by p2TA peptide 24 h later. Gastrointestinal tissue damage was evaluated by analysis of jejunum histopathology and immunohistochemistry for cell proliferation (Cyclin D1 and inflammation (COX-2 markers, as well as the presence of macrophages (F4/80. Pro-inflammatory cytokines IL-6 and KC as well as fibrinogen were quantified in plasma samples obtained from the same mice. Our results demonstrated that administration of p2TA peptide significantly reduced the irradiation-induced increase of IL-6 and fibrinogen in plasma 7 days after exposure. Seven days after total body irradiation with 8 Gy of gamma rays numbers of intestinal crypt cells were reduced and villi were shorter in irradiated animals compared to the controls. The p2TA peptide delivery 24 h after irradiation led to improved morphology of villi and crypts, increased Cyclin D1 expression, decreased COX-2 staining and decreased numbers of macrophages in small intestine of irradiated mice. Our study suggests that attenuation of CD28 signaling is a promising therapeutic approach for mitigation of radiation-induced tissue injury.

  13. Taxonomy of P2P Applications

    NARCIS (Netherlands)

    Brands, E.H.T.B.; Karagiannis, Georgios

    2009-01-01

    Peer-to-peer (p2p) networks have gained immense popularity in recent years and the number of services they provide continuously rises. Where p2p-networks were formerly known as file-sharing networks, p2p is now also used for services like VoIP and IPTV. With so many different p2p applications and

  14. Procedures to characterize and study P2Z/P2X7 purinoceptor: flow cytometry as a promising practical, reliable tool

    Directory of Open Access Journals (Sweden)

    Nihei Oscar Kenji

    2000-01-01

    Full Text Available The expression of P2Z/P2X7 purinoceptor in different cell types is well established. This receptor is a member of the ionotropic P2X receptor family, which is composed by seven cloned receptor subtypes (P2X1 - P2X7. Interestingly, the P2Z/P2X7 has a unique feature of being linked to a non-selective pore which allows the passage of molecules up to 900 Da depending on the cell type. Early studies of P2Z/P2X7 purinoceptor were exclusively based on classical pharmacological studies but the recent tools of molecular biology have enriched the analysis of the receptor expression. The majority of assays and techniques chosen so far to study the expression of P2Z/P2X7 receptor explore directly or indirectly the effects of the opening of P2Z/P2X7 linked pore. In this review we describe the main techniques used to study the expression and functionality of P2Z/P2X7 receptor. Additionally, the increasing need and importance of a multifunctional analysis of P2Z/P2X7 expression based on flow cytometry technology is discussed, as well as the adoption of a more complete analysis of P2Z/P2X7 expression involving different techniques.

  15. p38 MAPK Mediates Glial P2X7R-Neuronal P2Y1R Inhibitory Control of P2X3R Expression in Dorsal Root Ganglion Neurons.

    Science.gov (United States)

    Chen, Yong; Li, Guangwen; Huang, Li-Yen Mae

    2015-01-01

    We have previously shown that endogenously active purinergic P2X7 receptors (P2X7Rs) in satellite glial cells of dorsal root ganglia (DRGs) stimulate ATP release. The ATP activates P2Y1Rs located in the enwrapped neuronal somata, resulting in down-regulation of P2X3Rs. This P2X7R-P2Y1-P2X3R inhibitory control significantly reduces P2X3R-mediated nociceptive responses. The underlying mechanism by which the activation of P2Y1Rs inhibits the expression of P2X3Rs remains unexplored. Examining the effect of the activation of p38 mitogen-activated protein kinase on the expression of P2X3Rs in DRGs, we found that the p38 activator, anisomycin (Anis), reduced the expression of P2X3Rs. Blocking the activity of SGCs by the glial Krebs cycle inhibitor, fluorocitrate, did not change the effect of Anis. These results suggest that neuronal p38 plays a major role in the inhibition of P2X3R expression. Western blotting analyses showed that inhibiting P2Y1Rs by MRS2179 (MRS) or blocking P2X7Rs by either oxATP or A740003 reduced pp38 and increased P2X3R expression in DRGs. These results are further supported by the immunohistochemical study showing that P2X7R and P2Y1R antagonists reduce the percentage of pp38-positive neurons. These observations suggest that activation of P2X7Rs and P2Y1Rs promotes p38 activity to exert inhibitory control on P2X3R expression. Since activation of p38 by Anis in the presence of either A740003 or MRS could overcome the block of P2X7R-P2Y1R inhibitory control, p38 in DRG neurons is downstream of P2Y1Rs. In addition, inhibition of p38 by SB202190 was found to prevent the P2X7R and P2Y1R block of P2X3R expression and increase P2X3R-mediated nociceptive flinch behaviors. p38 in DRG neurons downstream of P2Y1R is necessary and sufficient for the P2X7R-P2Y1R inhibitory control of P2X3R expression. © 2015 Chen et al.

  16. Nanosized Selenium: A Novel Platform Technology to Prevent Bacterial Infections

    Science.gov (United States)

    Wang, Qi

    As an important category of bacterial infections, healthcare-associated infections (HAIs) are considered an increasing threat to the safety and health of patients worldwide. HAIs lead to extended hospital stays, contribute to increased medical costs, and are a significant cause of morbidity and mortality. In the United States, infections encountered in the hospital or a health care facility affect more than 1.7 million patients, cost 35.7 billion to 45 billion, and contribute to 88,000 deaths in hospitals annually. The most conventional and widely accepted method to fight against bacterial infections is using antibiotics. However, because of the widespread and sometimes inappropriate use of antibiotics, many strains of bacteria have rapidly developed antibiotic resistance. Those new, stronger bacteria pose serious, worldwide threats to public health and welfare. In 2014, the World Health Organization (WHO) reported antibiotic resistance as a global serious threat that is no longer a prediction for the future but is now reality. It has the potential to affect anyone, of any age, in any country. The most effective strategy to prevent antibiotic resistance is minimizing the use of antibiotics. In recent years, nanomaterials have been investigated as one of the potential substitutes of antibiotics. As a result of their vastly increased ratio of surface area to volume, nanomaterials will likely exert a stronger interaction with bacteria which may affect bacterial growth and propagation. A major concern of most existing antibacterial nanomaterials, like silver nanoparticles, is their potential toxicity. But selenium is a non-metallic material and a required nutrition for the human body, which is recommended by the FDA at a 53 to 60 μg daily intake. Nanosized selenium is considered to be healthier and less toxic compared with many metal-based nanomaterials due to the generation of reactive oxygen species from metals, especially heavy metals. Therefore, the objectives of

  17. The Social Impact of P2P Systems

    Science.gov (United States)

    Glorioso, Andrea; Pagallo, Ugo; Ruffo, Giancarlo

    The chapter deals with the social impact of P2P systems in light of a bidirectional connection by which technological developments influence, in a complex and often unpredictable way, the social environment whereas the dynamic evolution of the latter does affect technological progress. From this perspective, the aim is to deepen legal issues, sociological trends, economical aspects, and political dimensions of P2P technology, along with some of its next possible outputs, in order to assess one of the most compelling alternatives to the traditional frame of highly centralized human interaction.

  18. Digital Suicide Prevention: Can Technology Become a Game-changer?

    Science.gov (United States)

    Vahabzadeh, Arshya; Sahin, Ned; Kalali, Amir

    2016-01-01

    Suicide continues to be a leading cause of death and has been recognized as a significant public health issue. Rapid advances in data science can provide us with useful tools for suicide prevention, and help to dynamically assess suicide risk in quantitative data-driven ways. In this article, the authors highlight the most current international research in digital suicide prevention, including the use of machine learning, smartphone applications, and wearable sensor driven systems. The authors also discuss future opportunities for digital suicide prevention, and propose a novel Sensor-driven Mental State Assessment System.

  19. Reducing security risk using data loss prevention technology.

    Science.gov (United States)

    Beeskow, John

    2015-11-01

    Data loss/leakage protection (DLP) technology seeks to improve data security by answering three fundamental questions: > Where are confidential data stored? > Who is accessing the information? > How are data being handled?

  20. Identity theft and consumers' reaction to preventive technological innovations.

    Science.gov (United States)

    Ainscough, Thomas L; Brody, Richard G; Trocchia, Philip J

    2007-08-01

    The use of identification technology by commercial entities has broad and, for some consumers, disturbing social implications. This two-phase study was done to specify consumers' concerns regarding various identification technologies which may be encountered in retail environments. From the qualitative findings, a 26-item survey was constructed to quantify identified areas of concern with 303 survey participants (147 women and 156 men), whose mean age category was 30 to 39 years. Using exploratory factor analysis (principal components with varimax rotation), five dimensions of consumers' concern emerged: privacy, ethics, health, humanity, and complexity.

  1. Preventing unauthorized use of firearms by implementing use control technologies

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, D.R.

    1995-07-01

    A goal among many law enforcement and security professionals, and the National Institute of Justice, is to decrease the risk that an officer or security guard may encounter. One risk that officers confront is unpredictable persons who sometimes try to gain control of the officer`s firearm. The addition of user-recognizing-and-authorizing technologies to a firearm could eliminate the capability of an unauthorized user from firing an officer`s firearm. Sandia National Laboratories has been active in the research and development of nuclear security systems that include access and use control technologies. Sandia is being sponsored by the National Institute of Justice to perform a research and development project to determine the feasibility of a user authorized firearm, or {open_quotes}smart gun.{close_quotes} The focus group for the research is law enforcement officers because of the number of firearm take aways that have occurred in the past and the severe use requirements placed on their firearms. A comprehensive look at the problem of weapon take aways in the United States was conducted using information available from the Federal Bureau of Investigation and other law enforcement sources. An investigation into the end user requirements for smart gun technologies has been completed. During the remainder of the project, the user requirements are being transformed into engineering requirements. which will then be used to evaluate numerous technologies that could be used in a smart gun. Demonstration models will be made of the most promising technologies. Other potential applications are remote enabling and disabling of firearms, transportation of prisoners by corrections officers, military use in operations other than war, and use by private citizens.

  2. P2P Data Management in Mobile Wireless Sensor Network

    Directory of Open Access Journals (Sweden)

    Nida Sahar Sayeda

    2013-04-01

    Full Text Available The rapid growth in wireless technologies has made wireless communication an important source for transporting data across different domains. In the same way, there are possibilities of many potential applications that can be deployed using WSNs (Wireless Sensor Networks. However, very limited applications are deployed in real life due to the uncertainty and dynamics of the environment and scare resources. This makes data management in WSN a challenging area to find an approach that suits its characteristics. Currently, the trend is to find efficient data management schemes using evolving technologies, i.e. P2P (Peer-to-Peer systems. Many P2P approaches have been applied in WSNs to carry out the data management due to similarities between WSN and P2P. With the similarities, there are differences too that makes P2P protocols inefficient in WSNs. Furthermore, to increase the efficiency and to exploit the delay tolerant nature of WSNs, where ever possible, the mobile WSNs are gaining importance. Thus, creating a three dimensional problem space to consider, i.e. mobility, WSNs and P2P. In this paper, an efficient algorithm is proposed for data management using P2P techniques for mobile WSNs. The real world implementation and deployment of proposed algorithm is also presented

  3. Isoinertial technology for rehabilitation and prevention of muscle injuries of soccer players: literature review

    Directory of Open Access Journals (Sweden)

    Laura del Pilar Prieto-Mondragón

    2016-07-01

    Conclusions: Isoinertial technology is a useful tool for treating and preventing injuries, as well as for the development of physical qualities. However, it is necessary to work on protocols that allow unifying its usage parameters so that it can be included in prevention programs.

  4. FY 1999 Pollution Prevention and Environmental Technology Division

    Science.gov (United States)

    2000-01-01

    Soil and Groundwater Using GC- NPD . CRREL Special Report (In Press). ♦ FIELDING BIOTREATMENT TECHNOLOGIES UNDER THE AGRICULTURE-BASED...Environmental Protection Agency’s National Priorities List. The Dole Food Company, in partnership with the Navy in Hawaii, will field-test a 1.3-acre...the same food -grade biodegradable surfactants showed faster initial reduction of TNT, but its byproducts accumulated in the reactor for longer

  5. Silica scale prevention technology using organic additive, Geogard SX

    Energy Technology Data Exchange (ETDEWEB)

    Baltazar, Almario; Garcia, Serafin; Solis, Ramonito; Fragata, Jimmy; Ellseworth, Lucero; Llenarizas, Leonardo; Tabuena, Joseph Erwin (PNOC Energy Development Corporation, Makati City (Philippines))

    1998-09-15

    A field trial on the application of an organic additive, phosphino carboxylic acid copolymer, was conducted in a geothermal system to evaluate its effectiveness in preventing silica deposition from brine containing ultra high silica concentration (1000-1300 ppm). Low polymer concentration was applied for about five months, and treatment efficiency based on silica concentrations in various sampling points ranged from 64 to 98%. Treatment efficiency improved as a function of time. Massive silica scaling in the fluid collection and disposal system was minimized.

  6. Fall prevention intervention technologies: A conceptual framework and survey of the state of the art.

    Science.gov (United States)

    Hamm, Julian; Money, Arthur G; Atwal, Anita; Paraskevopoulos, Ioannis

    2016-02-01

    In recent years, an ever increasing range of technology-based applications have been developed with the goal of assisting in the delivery of more effective and efficient fall prevention interventions. Whilst there have been a number of studies that have surveyed technologies for a particular sub-domain of fall prevention, there is no existing research which surveys the full spectrum of falls prevention interventions and characterises the range of technologies that have augmented this landscape. This study presents a conceptual framework and survey of the state of the art of technology-based fall prevention systems which is derived from a systematic template analysis of studies presented in contemporary research literature. The framework proposes four broad categories of fall prevention intervention system: Pre-fall prevention; Post-fall prevention; Fall injury prevention; Cross-fall prevention. Other categories include, Application type, Technology deployment platform, Information sources, Deployment environment, User interface type, and Collaborative function. After presenting the conceptual framework, a detailed survey of the state of the art is presented as a function of the proposed framework. A number of research challenges emerge as a result of surveying the research literature, which include a need for: new systems that focus on overcoming extrinsic falls risk factors; systems that support the environmental risk assessment process; systems that enable patients and practitioners to develop more collaborative relationships and engage in shared decision making during falls risk assessment and prevention activities. In response to these challenges, recommendations and future research directions are proposed to overcome each respective challenge. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Development of rock fall prevention and protection technology

    Energy Technology Data Exchange (ETDEWEB)

    Tomita, S. [Japan Coal Energy Center (Japan). Resources Dept.

    2006-03-15

    Rock falls are frequently occurring events in coal mines. They are profoundly influenced by the geological conditions of the coal mine and thus very difficult to prevent altogether. With the system that is being developed at present by JCOAL it will be possible to ascertain the roof conditions to some extent. Such prediction should make it possible to prevent major accidents that would otherwise claim lives. The use of this system is also capable of improving the efficiency of mining operations. The system under development involves a logging system for detecting cracks and discontinuities which consists of a Transmaster 1 bolting machine, a data logger and an analysis software program. Several methods are being researched to obtain data for predicting and monitoring rock fall. Field tests have been conducted at the Kushiro Coal Mine in Japan and the Ulan Coal Mine in NSW, Australia to gather data by PCs through the internet. Data from microtremors and P-wave velocities are being analysed to give early indication of rock fall. 5 refs., 7 figs.

  8. P2X receptors in epithelia

    DEFF Research Database (Denmark)

    Leipziger, Jens Georg

    2015-01-01

    P2X receptors are ubiquitously expressed in all epithelial tissues but their functional roles are less well studied. Here we review the current state of knowledge by focusing on functional effects of P2X receptor in secretory and in absorptive tissues. In glandular tissue like the parotid gland b...

  9. Use of Technology for HIV Prevention Among Adolescent and Adult Women in the United States.

    Science.gov (United States)

    Blackstock, Oni J; Patel, Viraj V; Cunningham, Chinazo O

    2015-12-01

    Although the proportion of new HIV infections in the USA among women has decreased over the last few years, still, approximately 20 % of new infections occur annually among adolescent and adult women. The development of effective evidence-based prevention interventions remains an important approach to further decreasing these numbers. Technology-delivered prevention interventions hold tremendous potential due, in part, to their ability to reach beyond the walls of brick-and-mortar intervention sites to engage individuals where they are. While most technology-delivered interventions have focused on adolescents and men who have sex with men, much fewer have specifically targeted adolescent or adult women despite evidence showing that interventions tailored to specific target populations are most effective. We summarize the recently published literature on technology-delivered HIV prevention interventions for US adolescent and adult women and provide suggestions for next steps in this nascent but emergent area of prevention research.

  10. CONSTRUCTED WETLAND TECHNOLOGY TO PREVENT WATER RESOURCES POLLUTION

    Directory of Open Access Journals (Sweden)

    Zeki Gökalp

    2016-07-01

    Full Text Available Discharge of untreated waste waters into surface waters creates significant pollution in these resources. Wastewaters are most of the time discharged into seas, rivers and other water bodies without any treatments due to high treatment costs both in Turkey and throughout the world. Constructed wetlands, also called as natural treatment systems, are used as an alternative treatment system to conventional high-cost treatment systems because of their low construction, operation and maintenance costs, energy demands, easy operation and low sludge generation. Today, constructed wetland systems are largely used to treat domestic wastewaters, agricultural wastewaters, industrial wastewater and runoff waters and ultimately to prevent water pollution and to improve water quality of receiving water bodies. In present study, currently implemented practices in design, construction, operation and maintenance of constructed wetlands were assessed and potential mistakes made in different phases these systems were pointed out and possible solutions were proposed to overcome these problems.

  11. Preventing Soft Texture Fish Fillets through Brine Injection Technology

    Directory of Open Access Journals (Sweden)

    Silvana Dinaintang Harikedua

    2017-01-01

    Full Text Available An exploratory study was conducted to determine if multineedle injection technology could deliver protease inhibitor ingredients into fish fillets at sufficient levels to inhibit protease activity. Pacific whiting is used as a model in this study. Fillet treatments (n=8/treatment included noninjection (C, injection of base brine containing 3% salt and 3% sodium tripolyphosphate (B, injection of base brine and 3% egg white (BEW, and injection of base brine, 0.1% xanthan gum, and 3% dried potato extract (BPE. Xanthan gum was used as a suspension aid. Actual brine incorporation was 12.2±0.5%. Cathepsin L activity was evaluated at pH 5.5 (optimal pH and ultimate pH. Quality measures evaluated included CIE Lab color, shear force, and lipid oxidation. Fillets injected with BEW and BPE were significantly lower in cathepsin L activity when measured at pH 5.5. BEW and BPE fillets were darker in appearance than B or C fillets. Untreated fillets (C had higher variability in shear force value than treated fillets. There was no effect of treatment on lipid oxidation. Results suggested that injection technology can be utilized to incorporate protease inhibitor ingredients (3% EW or 3% PE at levels sufficient to reduce cathepsin L activity in Pacific whiting fillets.

  12. Does smart home technology prevent falls in community-dwelling older adults: a literature review.

    Science.gov (United States)

    Pietrzak, Eva; Cotea, Cristina; Pullman, Stephen

    2014-01-01

    Falls in older Australians are an increasingly costly public health issue, driving the development of novel modes of intervention, especially those that rely on computer-driven technologies. The aim of this paper was to gain an understanding of the state of the art of research on smart homes and computer-based monitoring technologies to prevent and detect falls in the community-dwelling elderly. Cochrane, Medline, Embase and Google databases were searched for articles on fall prevention in the elderly using pre-specified search terms. Additional papers were searched for in the reference lists of relevant reviews and by the process of 'snowballing'. Only studies that investigated outcomes related to falling such as fall prevention and detection, change in participants' fear of falling and attitudes towards monitoring technology were included. Nine papers fulfilled the inclusion criteria. The following outcomes were observed: (1) older adults' attitudes towards fall detectors and smart home technology are generally positive; (2) privacy concerns and intrusiveness of technology were perceived as less important to participants than their perception of health needs and (3) unfriendly and age-inappropriate design of the interface may be one of the deciding factors in not using the technology. So far, there is little evidence that using smart home technology may assist in fall prevention or detection, but there are some indications that it may increase older adults' confidence and sense of security, thus possibly enabling aging in place.

  13. A critical look at the function of the P2Y11 receptor

    DEFF Research Database (Denmark)

    Dreisig, Karin; Kornum, Birgitte Rahbek

    2016-01-01

    The P2Y11 receptor is a member of the purinergic receptor family. It has been overlooked, somewhat due to the lack of a P2ry11 gene orthologue in the murine genome, which prevents the generation of knockout mice, which have been so helpful for defining the roles of other P2Y receptors. Furthermor...

  14. Research of using mobile agents for information discovery in P2P networks

    International Nuclear Information System (INIS)

    Lan Yan; Yao Qing

    2003-01-01

    The technology of P2P is a new network-computing model that has great value of commerce and technology. After analyzing the current information discovery technology in P2P network, a new solution that is based on mobile agent is proposed. The mobile agent solution can reduce the need of bandwidth, be adapt to the dynamic of P2P network, and be asynchronous and be very fault tolerant. (authors)

  15. Characterization of P2P Systems

    Science.gov (United States)

    Stutzbach, Daniel; Rejaie, Reza

    The combination of large scale and geographically distributed nature of P2P system has led to their significant impact on the Internet. It is essential to characterize deployed P2P system for at least three reasons: (1) Accurately assessing their impact on the Internet, (2) identifying any performance bottleneck as well as any opportunity for performance improvement, (3) understanding user-driven dynamics in P2P systems. To characterize a P2P system, one needs to accurately capture snapshots of the resulting P2P overlay. This is challenging because the overlay is often large and dynamic. While the overlay is discovered by a crawler, it is changing which leads to a distorted view of the system. Capturing unbiased view of the traffic in the overlay is equally challenging because it is difficult to show that the captured behavior represent the observed behavior by all peers. In this chapter, we describe some of the fundamental problems in empirical characterization of widely deployed P2P systems. We present several examples to illustrate the effect of ad-hoc measurement/data collection on the resulting analysis/characterization. We then present two sampling techniques as a powerful approach to capture unbiased view of peer properties in a scalable fashion.

  16. Developing the FARSEEING Taxonomy of Technologies: Classification and description of technology use (including ICT) in falls prevention studies.

    Science.gov (United States)

    Boulton, Elisabeth; Hawley-Hague, Helen; Vereijken, Beatrix; Clifford, Amanda; Guldemond, Nick; Pfeiffer, Klaus; Hall, Alex; Chesani, Federico; Mellone, Sabato; Bourke, Alan; Todd, Chris

    2016-06-01

    Recent Cochrane reviews on falls and fall prevention have shown that it is possible to prevent falls in older adults living in the community and in care facilities. Technologies aimed at fall detection, assessment, prediction and prevention are emerging, yet there has been no consistency in describing or reporting on interventions using technologies. With the growth of eHealth and data driven interventions, a common language and classification is required. The FARSEEING Taxonomy of Technologies was developed as a tool for those in the field of biomedical informatics to classify and characterise components of studies and interventions. The Taxonomy Development Group (TDG) comprised experts from across Europe. Through face-to-face meetings and contributions via email, five domains were developed, modified and agreed: Approach; Base; Components of outcome measures; Descriptors of technologies; and Evaluation. Each domain included sub-domains and categories with accompanying definitions. The classification system was tested against published papers and further amendments undertaken, including development of an online tool. Six papers were classified by the TDG with levels of consensus recorded. Testing the taxonomy with papers highlighted difficulties in definitions across international healthcare systems, together with differences of TDG members' backgrounds. Definitions were clarified and amended accordingly, but some difficulties remained. The taxonomy and manual were large documents leading to a lengthy classification process. The development of the online application enabled a much simpler classification process, as categories and definitions appeared only when relevant. Overall consensus for the classified papers was 70.66%. Consensus scores increased as modifications were made to the taxonomy. The FARSEEING Taxonomy of Technologies presents a common language, which should now be adopted in the field of biomedical informatics. In developing the taxonomy as an

  17. Low-waste technology of prevention, decontamination and localization of radioactive contamination

    International Nuclear Information System (INIS)

    Kizhnerov, L. V.; Konstantinov, Ye. A.; Prokopenko, V. A.; Sorokin, N. M.

    1997-01-01

    The report presents the results of research in developing a low-waste technology of prevention, decontamination and localization of radioactive contamination founded on the of easily removed protective polymeric coating based on water and alcohol latexes and dispersion of polymers with special activating additives. The developed technology provides for the reduction of weakly fixed radioactive contamination of non-painted and painted surfaces to admissible levels (as a rule), it securely prevents and localizes contamination and does not generate secondary liquid radioactive wastes

  18. Technologies, Methodologies and Challenges in Network Intrusion Detection and Prevention Systems

    Directory of Open Access Journals (Sweden)

    Nicoleta STANCIU

    2013-01-01

    Full Text Available This paper presents an overview of the technologies and the methodologies used in Network Intrusion Detection and Prevention Systems (NIDPS. Intrusion Detection and Prevention System (IDPS technologies are differentiated by types of events that IDPSs can recognize, by types of devices that IDPSs monitor and by activity. NIDPSs monitor and analyze the streams of network packets in order to detect security incidents. The main methodology used by NIDPSs is protocol analysis. Protocol analysis requires good knowledge of the theory of the main protocols, their definition, how each protocol works.

  19. Ethical issues for late-stage trials of multipurpose prevention technologies for HIV and pregnancy

    Science.gov (United States)

    Cohen, Jessica A.; Mastroianni, Anna C.; Macklin, Ruth

    2014-01-01

    Multipurpose prevention technologies (MPTs) designed to simultaneously prevent pregnancy and HIV could provide urgently needed tools to address unmet sexual and reproductive health needs of women worldwide. Late-stage clinical trials will be complex given the need to demonstrate efficacy for HIV and contraceptive indications simultaneously from a single product. Currently, HIV and pregnancy prevention trials have distinctive design features that will need to be reconciled in MPT trials. This article identifies several ethical issues uniquely associated with this research that will benefit from future deliberation and guidance to ensure that this globally important research can proceed efficiently and expeditiously. PMID:25113651

  20. Thermoelastic properties of Zn3P2

    DEFF Research Database (Denmark)

    Gerward, Leif; Olsen, J. Staun; Waśkowska, A.

    2011-01-01

    The bulk modulus and thermal expansion of Zn3P2 has been investigated at pressures up to 21GPa and temperatures down to 100K. The experimental zero-pressure bulk modulus is 80.7 ± 1.8GPa, in accordance with the bulk modulus scaling and lattice properties of the related compound Cd3P2. A tetragonal...... to orthorhombic phase transformation occurs above 11GPa with a relative volume change of-7.1%. Values for the thermal expansion coefficient are reported at 293, 200 and 100K....

  1. A systematic review of technology-based interventions for unintentional injury prevention education and behaviour change.

    Science.gov (United States)

    Omaki, Elise; Rizzutti, Nicholas; Shields, Wendy; Zhu, Jeffrey; McDonald, Eileen; Stevens, Martha W; Gielen, Andrea

    2017-04-01

    The aims of this literature review are to (1) summarise how computer and mobile technology-based health behaviour change applications have been evaluated in unintentional injury prevention, (2) describe how these successes can be applied to injury-prevention programmes in the future and (3) identify research gaps. Studies included in this systematic review were education and behaviour change intervention trials and programme evaluations in which the intervention was delivered by either a computer or mobile technology and addressed an unintentional injury prevention topic. Articles were limited to those published in English and after 1990. Among the 44 technology-based injury-prevention studies included in this review, 16 studies evaluated locally hosted software programmes, 4 studies offered kiosk-based programmes, 11 evaluated remotely hosted internet programmes, 2 studies used mobile technology or portable devices and 11 studies evaluated virtual-reality interventions. Locally hosted software programmes and remotely hosted internet programmes consistently increased knowledge and behaviours. Kiosk programmes showed evidence of modest knowledge and behaviour gains. Both programmes using mobile technology improved behaviours. Virtual-reality programmes consistently improved behaviours, but there were little gains in knowledge. No studies evaluated text-messaging programmes dedicated to injury prevention. There is much potential for computer-based programmes to be used for injury-prevention behaviour change. The reviewed studies provide evidence that computer-based communication is effective in conveying information and influencing how participants think about an injury topic and adopt safety behaviours. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. Older adults' perceptions of technologies aimed at falls prevention, detection or monitoring: a systematic review.

    Science.gov (United States)

    Hawley-Hague, Helen; Boulton, Elisabeth; Hall, Alex; Pfeiffer, Klaus; Todd, Chris

    2014-06-01

    Over recent years a number of Information and Communication Technologies (ICTs) have emerged aiming at falls prevention, falls detection and alarms for use in case of fall. There are also a range of ICT interventions, which have been created or adapted to be pro-active in preventing falls, such as those which provide strength and balance training to older adults in the prevention of falls. However, there are issues related to the adoption and continued use of these technologies by older adults. This review provides an overview of older adults' perceptions of falls technologies. We undertook systematic searches of MEDLINE, EMBASE, CINAHL and PsychINFO, COMPENDEX and the Cochrane database. Key search terms included 'older adults', 'seniors', 'preference', 'attitudes' and a wide range of technologies, they also included the key word 'fall*'. We considered all studies that included older adults aged 50 and above. Studies had to include technologies related specifically to falls prevention, detection or monitoring. The Joanna Briggs Institute (JBI) tool and the Quality Assessment Tool for Quantitative Studies by the Effective Public Health Practice Project (EPHPP) were used. We identified 76 potentially relevant papers. Some 21 studies were considered for quality review. Twelve qualitative studies, three quantitative studies and 6 mixed methods studies were included. The literature related to technologies aimed at predicting, monitoring and preventing falls suggest that intrinsic factors related to older adults' attitudes around control, independence and perceived need/requirements for safety are important for their motivation to use and continue using technologies. Extrinsic factors such as usability, feedback gained and costs are important elements which support these attitudes and perceptions. Positive messages about the benefits of falls technologies for promoting healthy active ageing and independence are critical, as is ensuring that the technologies are simple

  3. Does smart home technology prevent falls in community-dwelling older adults: a literature review

    Directory of Open Access Journals (Sweden)

    Eva Pietrzak

    2014-04-01

    Full Text Available Background: Falls in older Australians are an increasingly costly public health issue, driving the development of novel modes of intervention, especially those that rely on computer-driven technologies. Objective: The aim of this paper was to gain an understanding of the state of the art of research on smart homes and computer-based monitoring technologies to prevent and detect falls in the community-dwelling elderly. Method: Cochrane, Medline, Embase and Google databases were searched for articles on fall prevention in the elderly using pre-specified search terms. Additional papers were searched for in the reference lists of relevant reviews and by the process of ‘snowballing’. Only studies that investigated outcomes related to falling such as fall prevention and detection, change in participants’ fear of falling and attitudes towards monitoring technology were included. Results: Nine papers fulfilled the inclusion criteria. The following outcomes were observed: (1 older adults’ attitudes towards fall detectors and smart home technology are generally positive; (2 privacy concerns and intrusiveness of technology were perceived as less important to participants than their perception of health needs and (3 unfriendly and age-inappropriate design of the interface may be one of the deciding factors in not using the technology. Conclusion: So far, there is little evidence that using smart home technology may assist in fall prevention or detection, but there are some indications that it may increase older adults’ confidence and sense of security, thus possibly enabling aging in place.

  4. Does smart home technology prevent falls in community-dwelling older adults: a literature review

    Directory of Open Access Journals (Sweden)

    Eva Pietrzak

    2014-06-01

    Full Text Available Background: Falls in older Australians are an increasingly costly public health issue, driving the development of novel modes of intervention, especially those that rely on computer-driven technologies.Objective: The aim of this paper was to gain an understanding of the state of the art of research on smart homes and computer-based monitoring technologies to prevent and detect falls in the community-dwelling elderly.Method: Cochrane, Medline, Embase and Google databases were searched for articles on fall prevention in the elderly using pre-specified search terms. Additional papers were searched for in the reference lists of relevant reviews and by the process of ‘snowballing’. Only studies that investigated outcomes related to falling such as fall prevention and detection, change in participants’ fear of falling and attitudes towards monitoring technology were included.Results: Nine papers fulfilled the inclusion criteria. The following outcomes were observed: (1 older adults’ attitudes towards fall detectors and smart home technology are generally positive; (2 privacy concerns and intrusiveness of technology were perceived as less important to participants than their perception of health needs and (3 unfriendly and age-inappropriate design of the interface may be one of the deciding factors in not using the technology.Conclusion: So far, there is little evidence that using smart home technology may assist in fall prevention or detection, but there are some indications that it may increase older adults’ confidence and sense of security, thus possibly enabling aging in place. 

  5. P2X Receptors and Synaptic Plasticity

    Czech Academy of Sciences Publication Activity Database

    Pankratov, Y.; Lalo, U.; Krishtal, A.; Verkhratsky, Alexei

    2009-01-01

    Roč. 158, č. 1 (2009), s. 137-148 ISSN 0306-4522 Institutional research plan: CEZ:AV0Z50390512 Keywords : ATP * P2X receptors * synaptic plasticity Subject RIV: FH - Neurology Impact factor: 3.292, year: 2009

  6. P2X receptory v bolesti

    Czech Academy of Sciences Publication Activity Database

    Jindřichová, Marie; Zemková, Hana

    2014-01-01

    Roč. 63, č. 2 (2014), s. 74-77 ISSN 1210-6313 R&D Projects: GA ČR(CZ) GPP304/12/P371 Institutional support: RVO:67985823 Keywords : extracellular ATP * purinergic P2X receptors * neuropathic pain Subject RIV: ED - Physiology

  7. Is gene technology in agriculture able to prevent hunger in the world?

    NARCIS (Netherlands)

    Goewie, E.A.

    2002-01-01

    The worldpopulation grows rapidly: the number of mouths to feed increases. Is ar agriculture without gene technology able to produce sufficiently in order to prevent hunger? Research indicates that hunger is not the result of short comings in agricultural outputs. It is however the result of

  8. Loss of Control Prevention and Recovery: Onboard Guidance, Control, and Systems Technologies

    Science.gov (United States)

    Belcastro, Christine M.

    2012-01-01

    Loss of control (LOC) is one of the largest contributors to fatal aircraft accidents worldwide. LOC accidents are complex in that they can result from numerous causal and contributing factors acting alone or (more often) in combination. These LOC hazards include vehicle impairment conditions, external disturbances; vehicle upset conditions, and inappropriate crew actions or responses. Hence, there is no single intervention strategy to prevent these accidents. NASA previously defined a comprehensive research and technology development approach for reducing LOC accidents and an associated integrated system concept. Onboard technologies for improved situation awareness, guidance, and control for LOC prevention and recovery are needed as part of this approach. Such systems should include: LOC hazards effects detection and mitigation; upset detection, prevention and recovery; and mitigation of combined hazards. NASA is conducting research in each of these areas. This paper provides an overview of this research, including the near-term LOC focus and associated analysis, as well as preliminary flight system architecture.

  9. Exploring Social Networking Technologies as Tools for HIV Prevention for Men Who Have Sex With Men.

    Science.gov (United States)

    Ramallo, Jorge; Kidder, Thomas; Albritton, Tashuna; Blick, Gary; Pachankis, John; Grandelski, Valen; Grandeleski, Valen; Kershaw, Trace

    2015-08-01

    Social networking technologies are influential among men who have sex with men (MSM) and may be an important strategy for HIV prevention. We conducted focus groups with HIV positive and negative participants. Almost all participants used social networking sites to meet new friends and sexual partners. The main obstacle to effective HIV prevention campaigns in social networking platforms was stigmatization based on homosexuality as well as HIV status. Persistent stigma associated with HIV status and disclosure was cited as a top reason for avoiding HIV-related conversations while meeting new partners using social technologies. Further, social networking sites have different social etiquettes and rules that may increase HIV risk by discouraging HIV status disclosure. Overall, successful interventions for MSM using social networking technologies must consider aspects of privacy, stigma, and social norms in order to enact HIV reduction among MSM.

  10. Waste minimization and pollution prevention technology transfer : the Airlie House Projects

    International Nuclear Information System (INIS)

    Gatrone, R.; McHenry, J.; Myron, H.; Thout, J. R.

    1998-01-01

    The Airlie House Pollution Prevention Technology Transfer Projects were a series of pilot projects developed for the US Department of Energy with the intention of transferring pollution prevention technology to the private sector. The concept was to develop small technology transfer initiatives in partnership with the private sector. Argonne National Laboratory developed three projects: the microscale chemistry in education project, the microscale cost benefit study project, and the Bethel New Life recycling trainee project. The two microscale chemistry projects focused on introducing microscale chemistry technologies to secondary and college education. These programs were inexpensive to develop and received excellent evaluations from participants and regulators. The Bethel New Life recycling trainee project provided training for two participants who helped identify recycling and source reduction opportunities in Argonne National Laboratory's solid waste stream. The pilot projects demonstrated that technology transfer initiatives can be developed and implemented with a small budget and within a short period of time. The essential components of the pilot projects were identifying target technologies that were already available, identifying target audiences, and focusing on achieving a limited but defined objective

  11. Interest in multipurpose prevention technologies to prevent HIV/STIs and unintended pregnancy among young women in the United States.

    Science.gov (United States)

    Hynes, Jenna S; Sales, Jessica M; Sheth, Anandi N; Lathrop, Eva; Haddad, Lisa B

    2018-03-01

    High rates of sexually transmitted infections (STIs) and unintended pregnancy suggest a role for multipurpose prevention technologies (MPTs) designed to combine contraception and infection prophylaxis into one unified method. This study aims to determine factors associated with interest in MPTs among US women. We administered a national cross-sectional survey via MTurk. Eligibility criteria included female gender, age 18-29 years, residence in the USA, and sexual activity with a male partner in the past three months. In total, 835 surveys were suitable for analysis. Bivariable and multivariable logistic regressions were performed to determine factors associated with interest in MPTs. Eighty-three percent of women were interested in MPTs. Factors associated with interest included oral sex in the past three months (aOR 1.87, 95% CI 1.07, 3.53), recent use of oral contraceptive pills (OCPs; aOR 1.78, 95% CI 1.08, 2.93), HIV test within one year (aOR 2.10, 95% CI 1.29, 3.40), and increased STI worry score (aOR 1.98, 95% CI 1.36, 2.86). No use of contraception in the past three months was associated with decreased interest in MPTs (aOR 0.31, 95% CI 0.17, 0.58). HIV risk factors including race were not associated with MPT interest. Our data show that young, sexually active, US women are interested in MPTs. Women who used contraception, specifically OCPs, or evidenced concern for infection were most likely to be interested in such a product. Women reporting unsafe sexual habits were less likely to be interested, highlighting the importance of HIV/STI prevention education. Women in the USA are interested in multipurpose prevention technologies, particularly those women who currently use contraception or are concerned about their risk of infection. Our results emphasize the importance of moving forward with MPT development as well as continued HIV/STI prevention education. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Measurement and analysis of P2P IPTV program resource.

    Science.gov (United States)

    Wang, Wenxian; Chen, Xingshu; Wang, Haizhou; Zhang, Qi; Wang, Cheng

    2014-01-01

    With the rapid development of P2P technology, P2P IPTV applications have received more and more attention. And program resource distribution is very important to P2P IPTV applications. In order to collect IPTV program resources, a distributed multi-protocol crawler is proposed. And the crawler has collected more than 13 million pieces of information of IPTV programs from 2009 to 2012. In addition, the distribution of IPTV programs is independent and incompact, resulting in chaos of program names, which obstructs searching and organizing programs. Thus, we focus on characteristic analysis of program resources, including the distributions of length of program names, the entropy of the character types, and hierarchy depth of programs. These analyses reveal the disorderly naming conventions of P2P IPTV programs. The analysis results can help to purify and extract useful information from chaotic names for better retrieval and accelerate automatic sorting of program and establishment of IPTV repository. In order to represent popularity of programs and to predict user behavior and popularity of hot programs over a period, we also put forward an analytical model of hot programs.

  13. Measurement and Analysis of P2P IPTV Program Resource

    Directory of Open Access Journals (Sweden)

    Wenxian Wang

    2014-01-01

    Full Text Available With the rapid development of P2P technology, P2P IPTV applications have received more and more attention. And program resource distribution is very important to P2P IPTV applications. In order to collect IPTV program resources, a distributed multi-protocol crawler is proposed. And the crawler has collected more than 13 million pieces of information of IPTV programs from 2009 to 2012. In addition, the distribution of IPTV programs is independent and incompact, resulting in chaos of program names, which obstructs searching and organizing programs. Thus, we focus on characteristic analysis of program resources, including the distributions of length of program names, the entropy of the character types, and hierarchy depth of programs. These analyses reveal the disorderly naming conventions of P2P IPTV programs. The analysis results can help to purify and extract useful information from chaotic names for better retrieval and accelerate automatic sorting of program and establishment of IPTV repository. In order to represent popularity of programs and to predict user behavior and popularity of hot programs over a period, we also put forward an analytical model of hot programs.

  14. Emerging Technologies to Prevent Pregnancy and Sexually Transmitted Infections in Women.

    Science.gov (United States)

    Seidman, Dominika; Hemmerling, Anke; Smith-McCune, Karen

    2016-05-01

    Worldwide, there continues to be a large unmet need for family planning and sexually transmitted infection (STI) prevention methods. Multipurpose prevention technology (MPT) is a general term encompassing any single prevention methodology targeting more than one STI (including HIV) and/or pregnancy. While innovation has been slow over the past several decades, recent scientific advances have resulted in new products entering clinical trials. This review focuses primarily on multipurpose technologies that are designed to prevent pregnancy and HIV. To examine the current state of MPTs, we outline key discoveries of biologic mechanisms that influence susceptibility of the female genital tract to HIV and STIs, and review the effects of hormonal contraception on HIV susceptibility. We discuss the state of currently available HIV prevention strategies for women, and their interactions with hormonal contraceptive products. Finally, we describe MPTs currently in preclinical and clinical trials and propose ongoing questions requiring research to help advance the field. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. PPADS and suramin as antagonists at cloned P2Y- and P2U-purinoceptors.

    Science.gov (United States)

    Charlton, S J; Brown, C A; Weisman, G A; Turner, J T; Erb, L; Boarder, M R

    1996-06-01

    1. The effect of suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) on the stimulation of phospholipase C in 1321N1 cells transfected with the human P2U-purinoceptor (h-P2U-1321N1 cells) or with the turkey P2Y-purinoceptor (t-P2Y-1321N1 cells) was investigated. 2-Methylthioadenosine triphosphate (2MeSATP) was used as the agonist at t-P2Y-1321N1 cells and uridine triphosphate (UTP) at h-P2U-1321N1 cells. 2. Suramin caused a parallel shift to the right of the concentration-response curves for 2MeSATP in the t-P2Y-1321N1 cells, yielding a Schild plot with a slope of 1.16 +/- 0.08 and a pA2 value of 5.77 +/- 0.11. 3. Suramin also caused a shift to the right of concentration-response curves for UTP in the h-P2U-1321N1 cells, and on Schild plots gave a slope different from unity (1.57 +/- 0.19) and an apparent pA2 value of 4.32 +/- 0.13. Suramin was therefore a less potent antagonist at the P2U-purinoceptor than the P2Y-purinoceptor. 4. In the presence of the ectonucleotidase inhibitor, ARL 67156 (6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP) there was no significant difference in the EC50 or shapes of curves with either cell type, and no difference in pA2 values for suramin. 5. PPADS caused an increase in the EC50 for 2MeSATP in the t-P2Y-1321N1 cells. The Schild plot had a slope different from unity (0.55 +/- 0.15) and an X-intercept corresponding to an apparent pA2 of 5.98 +/- 0.65. 6. PPADS up to 30 microM had no effect on the concentration-response curve for UTP with the h-P2U-1321N1 cells. 7. In conclusion, suramin and PPADS show clear differences in their action at the 2 receptor types, in each case being substantially more effective as an antagonist at the P2Y-purinoceptor than at the P2U-purinoceptor. Ectonucleotidase breakdown had little influence on the nature of the responses at the two receptor types, or in their differential sensitivity to suramin.

  16. Medicinal chemistry of adenosine, P2Y and P2X receptors.

    Science.gov (United States)

    Jacobson, Kenneth A; Müller, Christa E

    2016-05-01

    Pharmacological tool compounds are now available to define action at the adenosine (ARs), P2Y and P2X receptors. We present a selection of the most commonly used agents to study purines in the nervous system. Some of these compounds, including A1 and A3 AR agonists, P2Y1R and P2Y12R antagonists, and P2X3, P2X4 and P2X7 antagonists, are potentially of clinical use in treatment of disorders of the nervous system, such as chronic pain, neurodegeneration and brain injury. Agonists of the A2AAR and P2Y2R are already used clinically, P2Y12R antagonists are widely used antithrombotics and an antagonist of the A2AAR is approved in Japan for treating Parkinson's disease. The selectivity defined for some of the previously introduced compounds has been revised with updated pharmacological characterization, for example, various AR agonists and antagonists were deemed A1AR or A3AR selective based on human data, but species differences indicated a reduction in selectivity ratios in other species. Also, many of the P2R ligands still lack bioavailability due to charged groups or hydrolytic (either enzymatic or chemical) instability. X-ray crystallographic structures of AR and P2YRs have shifted the mode of ligand discovery to structure-based approaches rather than previous empirical approaches. The X-ray structures can be utilized either for in silico screening of chemically diverse libraries for the discovery of novel ligands or for enhancement of the properties of known ligands by chemical modification. Although X-ray structures of the zebrafish P2X4R have been reported, there is scant structural information about ligand recognition in these trimeric ion channels. In summary, there are definitive, selective agonists and antagonists for all of the ARs and some of the P2YRs; while the pharmacochemistry of P2XRs is still in nascent stages. The therapeutic potential of selectively modulating these receptors is continuing to gain interest in such fields as cancer, inflammation, pain

  17. The Effect of Technology-Mediated Diabetes Prevention Interventions on Weight: A Meta-Analysis.

    Science.gov (United States)

    Bian, Rachel R; Piatt, Gretchen A; Sen, Ananda; Plegue, Melissa A; De Michele, Mariana L; Hafez, Dina; Czuhajewski, Christina M; Buis, Lorraine R; Kaufman, Neal; Richardson, Caroline R

    2017-03-27

    Lifestyle interventions targeting weight loss, such as those delivered through the Diabetes Prevention Program, reduce the risk of developing type 2 diabetes. Technology-mediated interventions may be an option to help overcome barriers to program delivery, and to disseminate diabetes prevention programs on a larger scale. We conducted a meta-analysis to evaluate the effect of such technology-mediated interventions on weight loss. In this meta-analysis, six databases were searched to identify studies reporting weight change that used technology to mediate diet and exercise interventions, and targeted individuals at high risk for developing type 2 diabetes. Studies published between January 1, 2002 and August 4, 2016 were included. The search identified 1196 citations. Of those, 15 studies met the inclusion criteria and evaluated 18 technology-mediated intervention arms delivered to a total of 2774 participants. Study duration ranged from 12 weeks to 2 years. A random-effects meta-analysis showed a pooled weight loss effect of 3.76 kilograms (95% CI 2.8-4.7; Ptechnology-mediated intervention method was most efficacious. Technology-mediated diabetes prevention programs can result in clinically significant amounts of weight loss, as well as improvements in glycaemia in patients with prediabetes. Due to their potential for large-scale implementation, these interventions will play an important role in the dissemination of diabetes prevention programs. ©Rachel R Bian, Gretchen A Piatt, Ananda Sen, Melissa A Plegue, Mariana L De Michele, Dina Hafez, Christina M Czuhajewski, Lorraine R Buis, Neal Kaufman, Caroline R Richardson. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 27.03.2017.

  18. Full report: Assessment and opportunity identification of energy efficient pollution prevention technologies and processes

    Energy Technology Data Exchange (ETDEWEB)

    1994-11-01

    US industry produces about 12 billion tons of waste a year, or two-thirds of the waste generated in the US. The costs of handling and disposing of these wastes are significant, estimated to be between $25 and $43 billion in 1991, and represent an increase of 66% since 1986. US industry also uses about one-third of all energy consumed in the nation, which adds to the environmental burden. Industrial wastes affect the environmental well-being of the nation and, because of their growing costs, the competitive abilities of US industry. As part of a national effort to reduce industrial wastes, the US Congress passed the Energy Policy Act (EPAct, P.L. 102-486). Section 2108, subsections (b) and (c), of EPAct requires the Department of Energy (DOE) to identify opportunities to demonstrate energy efficient pollution prevention technologies and processes; to assess their availability and the energy, environmental, and cost effects of such technologies; and to report the results. Work for this report clearly pointed to two things, that there is insufficient data on wastes and that there is great breadth and diversity in the US industrial sector. This report identifies: information currently available on industrial sector waste streams, opportunities for demonstration of energy efficient pollution prevention technologies in two industries that produce significant amounts of waste--chemicals and petroleum, characteristics of waste reducing and energy saving technologies identifiable in the public literature, and potential barriers to adoption of waste reducing technologies by industry.

  19. Python passive network mapping P2NMAP

    CERN Document Server

    Hosmer, Chet

    2015-01-01

    Python Passive Network Mapping: P2NMAP is the first book to reveal a revolutionary and open source method for exposing nefarious network activity. The ""Heartbleed"" vulnerability has revealed significant weaknesses within enterprise environments related to the lack of a definitive mapping of network assets. In Python Passive Network Mapping, Chet Hosmer shows you how to effectively and definitively passively map networks. Active or probing methods to network mapping have traditionally been used, but they have many drawbacks - they can disrupt operations, crash systems, and - most important

  20. What drives successful implementation of pollution prevention and cleaner technology strategy? The role of innovative capability.

    Science.gov (United States)

    Bhupendra, Kumar Verma; Sangle, Shirish

    2015-05-15

    Firms that are dynamic and prepared to implement environmental strategies have a potential competitive advantage over their industry counterparts. Therefore, it is important to understand, what capabilities are required to implement proactive environmental strategies. The paper discusses the attributes of innovative capability required by firms in order to adopt pollution prevention and cleaner technology strategies. Empirical results show that process and behavioral innovativeness are required by firms to implement a pollution prevention strategy. In addition to process and behavioral innovativeness, firms need a top management with high risk-taking ability as well as market, product, and strategic innovativeness to implement a cleaner technology strategy. The paper proposes some important managerial implications on the basis of the above research findings. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Aligning product development and user perspectives: social-behavioural dimensions of multipurpose prevention technologies.

    Science.gov (United States)

    Brady, M; Tolley, E

    2014-10-01

    Multipurpose prevention technologies provide a compelling response to the multiple and reinforcing sexual and reproductive health risks faced by women globally. To ensure that this potential is realised, product-specific characteristics and their social-behavioural correlates must be considered early in the product development process. This paper provides an overview of the key user-related social and behavioural dimensions of three broad categories of multipurpose prevention technologies: 1) sustained release vaginal rings, 2) pericoital vaginal products, and 3) co-formulated or co-administered injectables. The authors build upon the broad parameters of Target Product Profiles for such products, aligning them with user perspective considerations. © 2014 Royal College of Obstetricians and Gynaecologists.

  2. Making the case for multipurpose prevention technologies: the socio-epidemiological rationale.

    Science.gov (United States)

    Boonstra, H; Barot, S; Lusti-Narasimhan, M

    2014-10-01

    This paper summarises the public health rationale for multipurpose prevention technologies (MPTs) by examining recent epidemiological data and trends in sexual and reproductive health indicators. MPTs are products that combine protection against unintended pregnancy, HIV and other sexually transmitted infections. The successful introduction of new woman-controlled MPTs provides a compelling response to the multiple sexual and reproductive health risks that women face worldwide. © 2014 Royal College of Obstetricians and Gynaecologists.

  3. New technologies in the prevention and control of healthcare-associated infection.

    LENUS (Irish Health Repository)

    Humphreys, H

    2010-06-01

    The increased interest in healthcare-associated infection (HCAI) among the public, patients and politicians has led to the development of potential new approaches to its prevention by industrial concerns and others. Such developments include better methods of assessing hospital hygiene, enhanced decontamination of the healthcare environment, biosynthetic tissue alternatives, antibiotic-impregnated medical devices and information technology that can help improve professional practice. Although promising, many of these have not been adequately evaluated in the clinical setting, highlighting the need for greater collaboration between industry and infection prevention and control practitioners to maximise the benefit of new products and to complement conventional approaches to HCAI prevention such as education, professional practice and the provision of better facilities.

  4. Gay Men's Understanding and Education of New HIV Prevention Technologies in Vancouver, Canada.

    Science.gov (United States)

    Klassen, Benjamin J; Lachowsky, Nathan J; Lin, Sally Yue; Edward, Joshua B; Chown, Sarah A; Hogg, Robert S; Moore, David M; Roth, Eric A

    2017-10-01

    Effective rollout of HIV treatment-based prevention such as pre-exposure prophylaxis and treatment as prevention has been hampered by poor education, limited acceptability, and stigma among gay men. We undertook a thematic analysis regarding the education sources and acceptability of these New Prevention Technologies (NPTs) using 15 semistructured interviews with gay men in Vancouver, Canada, who were early adopters of NPTs. NPT education was derived from a variety of sources, including the Internet, health care providers, community organizations, sexual partners, and peers; participants also emphasized their own capacities as learners and educators. Acceptable forms of NPT education featured high-quality factual information, personal testimony, and easy access. Stigma was highlighted as a major barrier. For public health, policy makers, and gay communities to optimize the personal and population benefits of NPTs, there is a need for increased community support and dialogue, antistigma efforts, early NPT adopter testimony, and personalized implementation strategies.

  5. From P2P to Web services and grids peers in a client/server world

    CERN Document Server

    Taylor, Ian J

    2005-01-01

    Provides an overview of peer-to-peer (P2P) technologies that have revolutionized the way we think about distributed computing and the internet. This book compares these technologies to alternative solutions, most notably web services and Grid computing but also other technologies, such as client/server based systems and agent technologies.

  6. [Parents' actions for prevention of arterial hypertension educational technology for health].

    Science.gov (United States)

    Santos, Zélia Maria de Sousa Araújo; Caetano, Joselany Afio; Moreira, Francisco Getúlio Alves

    2011-11-01

    This participatory research aimed to evaluate behavioral changes in fifteen parents of pre-school children to prevent the risk factors of arterial hypertension, by applying education technology for health that is based on the Health Beliefs Model at a private school in Fortaleza, State of Ceará, Brazil. The field research was carried out through educational workshops and data collection through questionnaires and interviews. After organizing the data into categories, analysis was based on the premises of health education. Through the application of education technology for health, significant changes were observed in the parents' habits, besides the roles they assumed as agents of change and multipliers of educational actions in the family. Although difficulties arose in the process of change, the parents were motivated to prevent the risk factors of arterial hypertension in themselves and their children. Thus, education technology for health based on the Health Beliefs Model proved to be efficient, as significant behavioral changes occurred and the parents were motivated to prevent arterial hypertension by means of a healthy lifestyle.

  7. Military Parents' Personal Technology Usage and Interest in e-Health Information for Obesity Prevention.

    Science.gov (United States)

    Jai, Tun-Min; McCool, Barent N; Reed, Debra B

    2016-03-01

    U.S. military families are experiencing high obesity rates similar to the civilian population. The Department of Defense's Military Health System (MHS) is one of the largest healthcare providers in the United States, serving approximately 9.2 million active duty service members, retirees, spouses, and children. The annual cost to the MHS for morbidities associated with being overweight exceeds $1 billion. The preschool age has been suggested as an opportune time to intervene for the prevention of obesity. Thus, this study investigated the current level of technology usage by military service member families and assessed their needs and interests in health/nutrition information. This needs assessment is crucial for researchers/educators to design further studies and intervention programs for obesity prevention in military families with young children. In total, 288 military parents (233 Army and 55 Air Force) at two military bases whose children were enrolled in military childcare centers in the southwestern United States participated in a Technology Usage in Military Family (TUMF) survey in 2013. Overall, both bases presented similar technology usage patterns in terms of computer and mobile device usage on the Internet. Air Force base parents had a slightly higher knowledge level of nutrition/health information than Army base parents. The TUMF survey suggested practical ways such as mobile applications/Web sites, social networks, games, etc., that health educators can use to disseminate nutrition/health information for obesity prevention among military families with young children.

  8. Mobile Health Technology Interventions for Suicide Prevention: Protocol for a Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Melia, Ruth; Francis, Kady; Duggan, Jim; Bogue, John; O'Sullivan, Mary; Chambers, Derek; Young, Karen

    2018-01-26

    Previous research has reported that two of the major barriers to help-seeking for individuals at risk of suicide are stigma and geographical isolation. Mobile technology offers a potential means of delivering evidence-based interventions with greater specificity to the individual, and at the time that it is needed. Despite documented motivation by at-risk individuals to use mobile technology to track mental health and to support psychological interventions, there is a shortfall of outcomes data on the efficacy of mobile health (mHealth) technology on suicide-specific outcomes. The objective of this study is to develop a protocol for a systematic review and meta-analysis that aims to evaluate the effectiveness of mobile technology-based interventions for suicide prevention. The search includes the Cochrane Central Register of Controlled Trials (CENTRAL: The Cochrane Library), MEDLINE, Embase, PsycINFO, CRESP and relevant sources of gray literature. Studies that have evaluated psychological or nonpsychological interventions delivered via mobile computing and communication technology, and have suicidality as an outcome measure will be included. Two authors will independently extract data and assess the study suitability in accordance with the Cochrane Collaboration Risk of Bias Tool. Studies will be included if they measure at least one suicide outcome variable (ie, suicidal ideation, suicidal intent, nonsuicidal self-injurious behavior, suicidal behavior). Secondary outcomes will be measures of symptoms of depression. Where studies are sufficiently homogenous and reported outcomes are amenable for pooled synthesis, meta-analysis will be performed. A narrative synthesis will be conducted if the data is unsuitable for a meta-analysis. The review is in progress, with findings expected by summer 2018. To date, evaluations of mobile technology-based interventions in suicide prevention have focused on evaluating content as opposed to efficacy. Indeed, previous research has

  9. Technology-Based Innovations in Child Maltreatment Prevention Programs: Examples from SafeCare®

    Directory of Open Access Journals (Sweden)

    Melissa Cowart-Osborne

    2014-08-01

    Full Text Available Each year, hundreds of thousands of children in the U.S. are victims of child maltreatment. Experts recommend behavioral, skill-based parent training programs as a strategy for the prevention of child abuse and neglect. These programs can be enhanced using innovative technology strategies. This paper presents a brief history of the use of technology in SafeCare®, a home visiting program shown to prevent child neglect and physical abuse, and highlights current work that takes a technology-based hybrid approach to SafeCare delivery. With this unique approach, the provider brings a tablet computer to each session, and the parent interacts with the software to receive psychoeducation and modeling of target skills. The provider and parent then work together to practice the targeted skills until mastery is achieved. Initial findings from ongoing research of both of these strategies indicate that they show potential for improving engagement and use of positive parenting skills for parents and ease of implementation for providers. Future directions for technology enhancements in SafeCare are also presented.

  10. The P2X7 Receptor Supports Both Life and Death in Fibrogenic Pancreatic Stellate Cells

    DEFF Research Database (Denmark)

    Haanes, Kristian; Schwab, Albrecht; Novak, Ivana

    2012-01-01

    inhibitor az10606120. The P2X7 receptor-pore inhibitor A438079 partially prevented cell death induced by millimolar ATP concentrations. This study shows that ATP and P2X7 receptors are important regulators of PSC proliferation and death, and therefore might be potential targets for treatments of pancreatic...

  11. Prevention of Pressure Ulcers in the Acute Care Setting: New Innovations and Technologies.

    Science.gov (United States)

    Tran, Jacquelynn P; McLaughlin, Jillian M; Li, Ramon T; Phillips, Linda G

    2016-09-01

    Pressure ulcers (PUs) challenge many in the healthcare field requiring costly and complex care. PUs result from prolonged ischemia and subsequent soft-tissue injury caused by unrelieved pressure over a bony prominence. Proper risk assessment and implementation of prevention strategies for PUs are crucial to providing comprehensive care while reducing healthcare costs. The emphasis has led to the expansion of research in PU prevention technologies in the recent years. The aim of this review is to present an evidence-based summary of some of the new innovations in PU prevention. A literature search was performed. Articles were included if the article discussed the cost, prevalence, assessment, diagnosis, and/or prevention of PUs. The literature search was limited to 2013 to 2016. A total of 1393 potential studies were identified using the search criteria. Three hundred fifty-three articles were reviewed and when possible, preference for inclusion was given to those studies with a higher level of evidence or those discussing novel ideas/innovations. The summary of topics explored includes the following: the use of risk assessment scales as an adjunct in risk identification, the benefit of alternative support surfaces to aid in prevention as compared with standard hospital mattresses, effective repositioning strategies, silicone prophylactic dressing for shear reduction, microclimate control, nutritional considerations, use of electrical stimulation for spinal cord injury patients, and the importance of patient participation.

  12. TRI P2 and Automotive Suppliers: Supplier information specific to the automotive industry sector

    Science.gov (United States)

    TRI’s Pollution Prevention (P2) Search Tool is one source of information to identify how facilities work with their suppliers and how suppliers work with their customers to achieve environmental improvement.

  13. Fall-Prone Older People's Attitudes towards the Use of Virtual Reality Technology for Fall Prevention.

    Science.gov (United States)

    Dockx, Kim; Alcock, Lisa; Bekkers, Esther; Ginis, Pieter; Reelick, Miriam; Pelosin, Elisa; Lagravinese, Giovanna; Hausdorff, Jeffrey M; Mirelman, Anat; Rochester, Lynn; Nieuwboer, Alice

    2017-01-01

    Virtual reality (VR) technology is a relatively new rehabilitation tool that can deliver a combination of cognitive and motor training for fall prevention. The attitudes of older people to such training are currently unclear. This study aimed to investigate: (1) the attitudes of fall-prone older people towards fall prevention exercise with and without VR; (2) attitudinal changes after intervention with and without VR; and (3) user satisfaction following fall prevention exercise with and without VR. A total of 281 fall-prone older people were randomly assigned to an experimental group receiving treadmill training augmented by VR (TT+VR, n = 144) or a control group receiving treadmill training alone (TT, n = 137). Two questionnaires were used to measure (1) attitudes towards fall prevention exercise with and without VR (AQ); and (2) user satisfaction (USQ). AQ was evaluated at baseline and after intervention. USQ was measured after intervention only. The AQ revealed that most participants had positive attitudes towards fall prevention exercise at baseline (82.2%) and after intervention (80.6%; p = 0.144). In contrast, only 53.6% were enthusiastic about fall prevention exercise with VR at baseline. These attitudes positively changed after intervention (83.1%; p < 0.001), and 99.2% indicated that they enjoyed TT+VR. Correlation analyses showed that postintervention attitudes were strongly related to user satisfaction (USQ: r = 0.503; p < 0.001). Older people's attitudes towards fall prevention exercise with VR were positively influenced by their experience. From the perspective of the user, VR is an attractive training mode, and thus improving service provision for older people is important. © 2017 S. Karger AG, Basel.

  14. Multipurpose prevention technologies for sexual and reproductive health: mapping global needs for introduction of new preventive products.

    Science.gov (United States)

    Schelar, Erin; Polis, Chelsea B; Essam, Timothy; Looker, Katharine J; Bruni, Laia; Chrisman, Cara J; Manning, Judy

    2016-01-01

    Worldwide, women face sexual and reproductive health (SRH) risks including unintended pregnancy and sexually transmitted infections (STIs) including HIV. Multipurpose prevention technologies (MPTs) combine protection against two or more SRH risks into one product. Male and female condoms are the only currently available MPT products, but several other forms of MPTs are in development. We examined the global distribution of selected SRH issues to determine where various risks have the greatest geographical overlap. We examined four indicators relevant to MPTs in development: HIV prevalence, herpes simplex virus type 2 prevalence (HSV-2), human papillomavirus prevalence (HPV) and the proportion of women with unmet need for modern contraception. Using ArcGIS Desktop, we mapped these indicators individually and in combination on choropleth and graduated symbol maps. We conducted a principal components analysis to reduce data and enable visual mapping of all four indicators on one graphic to identify overlap. Our findings document the greatest overlapping risks in Sub-Saharan Africa, and we specify countries in greatest need by specific MPT indication. These results can inform strategic planning for MPT introduction, market segmentation and demand generation; data limitations also highlight the need for improved (non-HIV) STI surveillance globally. MPTs are products in development with the potential to empower women to prevent two or more SRH risks. Geographic analysis of overlapping SRH risks demonstrates particularly high need in Sub-Saharan Africa. This study can help to inform strategic planning for MPT introduction, market segmentation and demand generation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Efficacy of technology-based interventions for obesity prevention in adolescents: a systematic review

    Directory of Open Access Journals (Sweden)

    Chen JL

    2014-08-01

    Full Text Available Jyu-Lin Chen,1 Mary Ellen Wilkosz2 1Department of Family Health Care Nursing, School of Nursing, University of California, San Francisco, CA, 2Nursing Department, Sonoma State University, Rohnert Park, CA, USA Abstract: About one third of adolescents in the USA are overweight and/or obese. Obesity during the adolescent years is associated with many adverse health consequences, including type 2 diabetes, hypertension, hyperlipidemia, and psychosocial problems. Because of substantial advances in technologies and wide acceptance by adolescents, it is now possible to use technology for healthy weight management and prevention of obesity. This systematic review used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and aimed to evaluate the existing literature reported on the effectiveness of technology-based intervention (web-based, e-learning, and active video games in preventing obesity in adolescents. The primary aim of this review was to explore if components of specific interventions were associated with a reduction in body mass index. Research articles obtained from CINAHL, Embase, PubMed, PsycInfo, and the Cochrane database from1990 to 2014 were reviewed. A total of 131 published articles were identified, and 14 met the inclusion criteria of a randomized or nonrandomized clinical study with body mass index as primary outcome and/or secondary outcomes of diet/physical activity and/or psychosocial function, tested lifestyle interventions to prevent obesity, used technology, and studied adolescents (aged 12–18 years. The results indicated that six of 14 studies found body mass index and/or body fat decreased at short-term (less than 12 months follow-up. Six of eleven studies that examined physical activity or physical activity-related outcomes found an improved physical activity outcome (time playing active video games and increase in physical activity time, while five of seven studies which assessed dietary

  16. Exergame technology and interactive interventions for elderly fall prevention: A systematic literature review.

    Science.gov (United States)

    Choi, Sang D; Guo, Liangjie; Kang, Donghun; Xiong, Shuping

    2017-11-01

    Training balance and promoting physical activities in the elderly can contribute to fall-prevention. Due to the low adherence of conventional physical therapy, fall interventions through exergame technologies are emerging. The purpose of this review study is to synthesize the available research reported on exergame technology and interactive interventions for fall prevention in the older population. Twenty-five relevant papers retrieved from five major databases were critically reviewed and analyzed. Results showed that the most common exergaming device for fall intervention was Nintendo Wii, followed by Xbox Kinect. Even though the exergame intervention protocols and outcome measures for assessing intervention effectiveness varied, the accumulated evidences revealed that exergame interventions improved physical or cognitive functions in the elderly. However, it remains inconclusive whether or not the exergame-based intervention for the elderly fall prevention is superior to conventional physical therapy and the effect mechanism of the exergaming on elderly's balance ability is still unclear. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Efficacy of computer technology-based HIV prevention interventions: a meta-analysis.

    Science.gov (United States)

    Noar, Seth M; Black, Hulda G; Pierce, Larson B

    2009-01-02

    To conduct a meta-analysis of computer technology-based HIV prevention behavioral interventions aimed at increasing condom use among a variety of at-risk populations. Systematic review and meta-analysis of existing published and unpublished studies testing computer-based interventions. Meta-analytic techniques were used to compute and aggregate effect sizes for 12 randomized controlled trials that met inclusion criteria. Variables that had the potential to moderate intervention efficacy were also tested. The overall mean weighted effect size for condom use was d = 0.259 (95% confidence interval = 0.201, 0.317; Z = 8.74, P partners, and incident sexually transmitted diseases. In addition, interventions were significantly more efficacious when they were directed at men or women (versus mixed sex groups), utilized individualized tailoring, used a Stages of Change model, and had more intervention sessions. Computer technology-based HIV prevention interventions have similar efficacy to more traditional human-delivered interventions. Given their low cost to deliver, ability to customize intervention content, and flexible dissemination channels, they hold much promise for the future of HIV prevention.

  18. Preventing another Chernobyl: codes, practices, and the role of new technology

    International Nuclear Information System (INIS)

    Egan, J.R.

    1988-01-01

    Preventative steps to prevent and mitigate the consequences of a nuclear accident are considered. The national and international legislation now available is mentioned elsewhere in the book. This chapter discusses the role of codes of conduct and personal agreements which could also prevent nuclear accidents. It is suggested that a radical departure from existing nuclear technology is needed. In particular some definite goals and objectives are suggested. The first is that there should be no meltdowns - all reactors must be physically incapable of core meltdown or explosion under any circumstances. This would mean no huge emergency evacuation plans, no need for expensive emergency core cooling systems. No spiralling cost overruns, no nuclear waste problem, no more huge reactors too big for national electrical systems, no military complications, no intractable decommissionings and no quality control problems are also given as goals. Some of these goals could be achieved with inherently safe reactor designs, much smaller reactors and factory assembly, rather than on-site construction. Other suggestions are also made to achieve the proposed new nuclear technology. (U.K.)

  19. Prevention

    Science.gov (United States)

    ... Error processing SSI file About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

  20. Hypochlorous acid gel technology-Its impact on postprocedure treatment and scar prevention.

    Science.gov (United States)

    Gold, Michael H; Andriessen, Anneke; Dayan, Steven H; Fabi, Sabrina G; Lorenc, Z Paul; Henderson Berg, Meagan-Helen

    2017-06-01

    A pre-and postprocedure regime aimed at prevention of infection, reduction of inflammation and risk of scarring, is to enable optimal outcomes. The role of a hypochlorous acid containing spray and translucent scar gel formulation that combines modified silicon oil with hypochlorous acid, was explored for pre- and postprocedure treatment and scar management. For this purpose a literature review was conducted to explore the value of the technology used in pre-and postprocedural regimes. A panel of dermatologists and plastic surgeons who practice in the United States discussed the summarized search results, taking into account their current clinical practice. A nominal group process for consensus was used, followed by online reviews of the manuscript. Based on panel discussions, consensus was reached regarding clinical recommendations given for postprocedure treatment and scar management. The hypochlorous acid products are produced with electrolysis and are classified among biocidal substances. The technology has demonstrated efficacy and safety for pre-and postprocedure use. The safety of hypochlorous solution use demonstrated to be comparable to that of standard local antiseptics. Small studies demonstrated better results with the scar gel compared to silicone gel regarding the appearance of hypertrophic and keloid scars, relief of associated pruritus and pain. A postprocedure regime using this technology, aimed at preventing infection, reducing inflammation, and promoting healing is proposed to have benefits over current regimes as it appears to be effective, safe, and well tolerated. © 2017 Wiley Periodicals, Inc.

  1. Localized Multistreams for P2P Streaming

    Directory of Open Access Journals (Sweden)

    Majed Alhaisoni

    2010-01-01

    Full Text Available Streaming video over the Internet, including cellular networks, has now become a commonplace. Network operators typically use multicasting or variants of multiple unicasting to deliver streams to the user terminal in a controlled fashion. P2P streaming is an emerging alternative, which is theoretically more scalable but suffers from other issues arising from the dynamic nature of the system. Users' terminals become streaming nodes but they are not constantly connected. Another issue is that they are based on logical overlays, which are not optimized for the physical underlay infrastructure. An important proposition is to find effective ways to increase the resilience of the overlay whilst at the same time not conflicting with the network. In this article we look at the combination of two techniques, redundant streaming and locality awareness, in the context of both live and video-on-demand streaming. We introduce a new technique and assess it via a comparative, simulation-based study. We find that redundancy affects network utilization only marginally if traffic is kept at the edges via localization techniques.

  2. P2P XQuery and the StreetTiVo application

    NARCIS (Netherlands)

    P.A. Boncz (Peter); Y. Zhang (Ying)

    2007-01-01

    textabstractIn the AmbientDB project, we are building MonetDB/XQuery, an open-source XML DBMS (XDBMS) with support for distributed querying and P2P services. Our work is motivated by the hypothesis that P2P is a disruptive paradigm that should change the nature of database technology. Most of the

  3. Novel technologies for the prevention and treatment of dental caries: a patent survey.

    Science.gov (United States)

    Chen, Fu; Wang, Dong

    2010-05-01

    Dental caries is one of the most common preventable childhood diseases; people are susceptible to this ailment throughout their lifetime. In the US, 90% of late adolescents and young adults have dental caries, while 94% of all dentate adults had evidence of treated or untreated coronal caries. Dental caries is often not self-limiting and without proper care can progress until the tooth is destroyed. In this paper, the etiology of dental caries is briefly introduced. It is followed by a thorough review of patents and literatures on the recent development of various novel technologies for the prevention and treatment of dental caries. Recent advances in anti-plaque agents, including chemoprophylactic agents, antimicrobial peptides, vaccines, probiotics/replacement therapy and sugar substitutes, and remineralization agents including fluorides and casein phosphopeptides are analyzed. TAKE HOME MASSAGE: Both the discovery of new anti-caries agents and the development of dentotropic delivery systems will be the future focus of this research field.

  4. Research on preventive technologies for bed-separation water hazard in China coal mines

    Science.gov (United States)

    Gui, Herong; Tong, Shijie; Qiu, Weizhong; Lin, Manli

    2018-03-01

    Bed-separation water is one of the major water hazards in coal mines. Targeted researches on the preventive technologies are of paramount importance to safe mining. This article studied the restrictive effect of geological and mining factors, such as lithological properties of roof strata, coal seam inclination, water source to bed separations, roof management method, dimensions of mining working face, and mining progress, on the formation of bed-separation water hazard. The key techniques to prevent bed-separation water-related accidents include interception, diversion, destructing the buffer layer, grouting and backfilling, etc. The operation and efficiency of each technique are corroborated in field engineering cases. The results of this study will offer reference to countries with similar mining conditions in the researches on bed-separation water burst and hazard control in coal mines.

  5. Functional and molecular evidence for heteromeric association of P2Y1 receptor with P2Y2 and P2Y4 receptors in mouse granulocytes.

    Science.gov (United States)

    Ribeiro-Filho, Antonio Carlos; Buri, Marcus Vinicius; Barros, Carlos Castilho; Dreyfuss, Juliana Luporini; Nader, Helena Bonciani; Justo, Giselle Zenker; Craveiro, Rogério Bastos; Pesquero, João Bosco; Miranda, Antonio; Ferreira, Alice Teixeira; Paredes-Gamero, Edgar Julian

    2016-07-07

    All hematopoietic cells express P2 receptors, however pharmacological characteristics such as expression and affinity in granulocytes are unknown. Pharmacological characteristics of P2 receptors were evaluated by Ca(2+) measurements using Fura-2 fluorophore. P2 receptors expression were analyzed by flow cytometry and RT-PCR. P2 interaction were shown by coimmunoprecipitation, western blotting and FRET. Granulocytes were responsive to P2Y agonists, whereas P2X agonists were ineffective. Ca(2+) increase, elicited by ADP and UTP was dependent on intracellular stocks and sensitive to G-coupled receptor inhibition. Moreover, MRS2179, a specific antagonist of the P2Y1 receptor, abolished ADP response. Interestingly, ADP and UTP exhibited full heterologous desensitization, suggesting that these agonists interact with the same receptor. The heteromeric association between P2Y1 receptor and the P2Y2 and P2Y4 receptors was shown by immunoprecipitation and FRET analysis. Clear evidence of heteromeric association of P2Y receptors was found during the evaluation of P2 receptors present in mice granulocytes, which could impact in the classical pharmacology of P2Y receptors in granulocytes.

  6. Method for screening prevention and control measures and technologies based on groundwater pollution intensity assessment

    Energy Technology Data Exchange (ETDEWEB)

    Li, Juan, E-mail: lijuan@craes.org.cn [College of Water Sciences, Beijing Normal University, Beijing 100875 (China); Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Yang, Yang [College of Environment, Beijing Normal University, Beijing 100875 (China); Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Huan, Huan; Li, Mingxiao [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Xi, Beidou, E-mail: xibd413@yeah.net [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Lanzhou Jiaotong University, Lanzhou 730070 (China); Lv, Ningqing [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Wu, Yi [Guizhou Academy of Environmental Science and Designing, Guizhou 550000 (China); Xie, Yiwen, E-mail: qin3201@126.com [School of Chemical and Environmental Engineering, Dongguan University of Technology, Dongguan, 523808 (China); Li, Xiang; Yang, Jinjin [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China)

    2016-05-01

    This paper presents a system for determining the evaluation and gradation indices of groundwater pollution intensity (GPI). Considering the characteristics of the vadose zone and pollution sources, the system decides which anti-seepage measures should be implemented at the contaminated site. The pollution sources hazards (PSH) and groundwater intrinsic vulnerability (GIV) are graded by the revised Nemerow Pollution Index and an improved DRTAS model, respectively. GPI is evaluated and graded by a double-sided multi-factor coupling model, which is constructed by the matrix method. The contaminated sites are categorized as prior, ordinary, or common sites. From the GPI results, we develop guiding principles for preventing and removing pollution sources, procedural interruption and remediation, and end treatment and monitoring. Thus, we can select appropriate prevention and control technologies (PCT). To screen the technological schemes and optimize the traditional analytical hierarchy process (AHP), we adopt the technique for order preference by the similarity to ideal solution (TOPSIS) method. Our GPI approach and PCT screening are applied to three types of pollution sites: the refuse dump of a rare earth mine development project (a potential pollution source), a chromium slag dump, and a landfill (existing pollution sources). These three sites are identified as ordinary, prior, and ordinary sites, respectively. The anti-seepage materials at the refuse dump should perform as effectively as a 1.5-m-thick clay bed. The chromium slag dump should be preferentially treated by soil flushing and in situ chemical remediation. The landfill should be treated by natural attenuation technology. The proposed PCT screening approach was compared with conventional screening methods results at the three sites and proved feasible and effective. The proposed method can provide technical support for the monitoring and management of groundwater pollution in China. - Highlights: • An

  7. The Use of Assessment Center Technology for the Prevention and Reduction of Professional Burnout

    Directory of Open Access Journals (Sweden)

    Stalnova I.A.,

    2014-08-01

    Full Text Available Dynamism of professional activity, increasing workload and working time shortage, high social responsibility for results and other factors increase the probability of formation of burnout in government employees. This actualizes the search for new forms and methods of professional qualification of government employees based on an assessment of their psychological qualities. We discuss the problem of professional and personal burnout in Rosreestr employees, reveal the symptoms of this syndrome. As a tool for preventing and reducing the negative impact of professional deformation in Rosreestr workers, we propose the use of assessment center technology successfully tested in the international practice and requiring adaptation to Russian realities.

  8. NASA's Corrosion Technology Laboratory at the Kennedy Space Center: Anticipating, Managing, and Preventing Corrosion

    Science.gov (United States)

    Calle, Luz Marina

    2015-01-01

    The marine environment at NASAs Kennedy Space Center (KSC) has been documented by ASM International (formerly American Society for Metals) as the most corrosive in North America. With the introduction of the Space Shuttle in 1981, the already highly corrosive conditions at the launch pads were rendered even more severe by the highly corrosive hydrochloric acid (HCl) generated by the solid rocket boosters (SRBs). Numerous failures at the launch pads are caused by corrosion. The structural integrity of ground infrastructure and flight hardware is critical to the success, safety, cost, and sustainability of space missions. NASA has over fifty years of experience dealing with unexpected failures caused by corrosion and has developed expertise in corrosion control in the launch and other environments. The Corrosion Technology Laboratory at KSC evolved, from what started as an atmospheric exposure test site near NASAs launch pads, into a capability that provides technical innovations and engineering services in all areas of corrosion for NASA, external partners, and customers.This paper provides a chronological overview of NASAs role in anticipating, managing, and preventing corrosion in highly corrosive environments. One important challenge in managing and preventing corrosion involves the detrimental impact on humans and the environment of what have been very effective corrosion control strategies. This challenge has motivated the development of new corrosion control technologies that are more effective and environmentally friendly. Strategies for improved corrosion protection and durability can have a huge impact on the economic sustainability of human spaceflight operations.

  9. Gait and balance in the aging population: Fall prevention using innovation and technology.

    Science.gov (United States)

    Khanuja, Kavisha; Joki, Jaclyn; Bachmann, Gloria; Cuccurullo, Sara

    2018-04-01

    On a global basis, adults 65 years of age and older experience falls more frequently than younger individuals, and these often result in severe injuries as well as increased healthcare costs. Gait and balance disorders in this population are among the most common causes of falls and negatively influence quality of life and survivorship. Although falls are a major public health problem and guidelines/recommendations are available to physicians, many are fully aware of different assessments, tools, and resources available for intervention. Given the risk for potentially devastating outcomes if severe injuries occur secondary to a fall, fall prevention strategies in clinical offices is a timely consideration in today's health care landscape. This paper presents a three-tier model, comprising assessment, prevention, and intervention, to highlight methods, proactive programs, and innovative tools and technology that have been developed for fall prevention. Awareness of these resources will enhance the clinician's ability to accurately assess balance and gait, which can improve physical function, and decrease the risk of falls for both average-risk and high-risk older adults. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. A fraud prevention policy: Its relevance and implication at a university of technology in South Africa

    Directory of Open Access Journals (Sweden)

    Amelia Rorwana

    2015-08-01

    Full Text Available Using research grants administrators and their clients (academic researchers as the lens, this paper investigated the relevance and implication of a fraud prevention policy at a University of Technology (UoT in South Africa. The paper adopted a quantitative approach in which closed-ended questions were complemented by open-ended questions in the survey questionnaire in the attempt to capture the perceptions of both research grants administrators and their clients on the relevance and implications of a fraud and irregularity prevention policy. The results indicate that both research grants administrators (71.4 %, and their clients (73% do not know if UoTx has a fraud and irregularity policy. While only 36% of research grants administrators indicated that they would feel safe reporting deceitful activities, a slight majority (59% of the clients reported same. With regards to the steps to follow to report fraudulent activity, it was noted that while all (100% the research grants administrators noted that they were clueless, ironically an overwhelming majority of their clients indicated otherwise. Notwithstanding, both research grants administrators and their clients (93% and 95% respectively concurred that a fraud prevention policy was necessary for UoTx. The implication is that having phenomenal controls that are not effectively publicized, monitored or worse still overridden by someone are useless.

  11. The cost-effectiveness of multi-purpose HIV and pregnancy prevention technologies in South Africa.

    Science.gov (United States)

    Quaife, Matthew; Terris-Prestholt, Fern; Eakle, Robyn; Cabrera Escobar, Maria A; Kilbourne-Brook, Maggie; Mvundura, Mercy; Meyer-Rath, Gesine; Delany-Moretlwe, Sinead; Vickerman, Peter

    2018-03-01

    A number of antiretroviral HIV prevention products are efficacious in preventing HIV infection. However, the sexual and reproductive health needs of many women extend beyond HIV prevention, and research is ongoing to develop multi-purpose prevention technologies (MPTs) that offer dual HIV and pregnancy protection. We do not yet know if these products will be an efficient use of constrained health resources. In this paper, we estimate the cost-effectiveness of combinations of candidate multi-purpose prevention technologies (MPTs), in South Africa among general population women and female sex workers (FSWs). We combined a cost model with a static model of product impact based on incidence data in South Africa to estimate the cost-effectiveness of five candidate co-formulated or co-provided MPTs: oral PrEP, intravaginal ring, injectable ARV, microbicide gel and SILCS diaphragm used in concert with gel. We accounted for the preferences of end-users by predicting uptake using a discrete choice experiment (DCE). Product availability and protection were systematically varied in five potential rollout scenarios. The impact model estimated the number of infections averted through decreased incidence due to product use over one year. The comparator for each scenario was current levels of male condom use, while a health system perspective was used to estimate discounted lifetime treatment costs averted per HIV infection. Product benefit was estimated in disability-adjusted life years (DALYs) averted. Benefits from contraception were incorporated through adjusting the uptake of these products based on the DCE and through estimating the costs averted from avoiding unwanted pregnancies. We explore the additional impact of STI protection through increased uptake in a sensitivity analysis. At central incidence rates, all single- and multi-purpose scenarios modelled were cost-effective among FSWs and women aged 16-24, at a governmental willingness-to-pay threshold of $1175/DALY

  12. University of Tennessee - Industry collaborative research and development in preventive maintenance technology

    International Nuclear Information System (INIS)

    Upadhyaya, B.R.

    1992-01-01

    The Preventive Maintenance Engineering Laboratory (PMEL) was inaugurated at the University of Tennessee Nuclear Engineering Department in September 1989. The startup funding was provided by Gilbert/Commonwealth, Inc. The purpose of PMEL is to identify maintenance-related problems in the power and process industries and to find their solutions through the development and application of emerging technologies. These include advanced digital signal processing, applied artificial intelligence (AI), artificial neural networks, and reliability based methods. The Laboratory activities are being expanded by the formation of an industrial consortium within the Measurement and Control Engineering Center at the University of Tennessee. Several research and development projects in preventive maintenance are being carried out. These include condition monitoring of air operated valves, automated diagnostics of motor operated valves, instrument calibration, verification, and estimation of expected residual life of electric motors using applied AI technology and reliability-based methods. The new methodology will be applied to other industrial subsystems. A long-term research and development project is being sponsored by the T.V.A. Nuclear Maintenance Department. The overall objective of the research program is to develop and apply advanced artificial intelligence and information processing methods to the problems of plant performance monitoring and preventive maintenance. The program includes the development of a workstation/PC-based, networking of plant information for easy access to operational and management personnel, implementation of a sensor verification system, monitoring of feedwater flow venturi fouling and heat rate balance, and integration of signal validation, command validation, and fault-tolerant control strategies

  13. Mobile technology for obesity prevention: a randomized pilot study in racial- and ethnic-minority girls.

    Science.gov (United States)

    Nollen, Nicole L; Mayo, Matthew S; Carlson, Susan E; Rapoff, Michael A; Goggin, Kathy J; Ellerbeck, Edward F

    2014-04-01

    Mobile technologies have wide-scale reach and disseminability, but no known studies have examined mobile technologies as a stand-alone tool to improve obesity-related behaviors of at-risk youth. To test a 12-week mobile technology intervention for use and estimate effect sizes for a fully powered trial. Fifty-one low-income, racial/ethnic-minority girls aged 9-14 years were randomized to a mobile technology (n=26) or control (n=25) condition. Both conditions lasted 12 weeks and targeted fruits/vegetables (FVs; Weeks 1-4); sugar-sweetened beverages (SSBs; Weeks 5-8), and screen time (Weeks 9-12). The mobile intervention prompted real-time goal setting and self-monitoring and provided tips, feedback, and positive reinforcement related to the target behaviors. Controls received the same content in a written manual but no prompting. Outcomes included device utilization and effect size estimates of FVs, SSBs, screen time, and BMI. Data were collected and analyzed in 2011-2012. Mobile technology girls used the program on 63% of days and exhibited trends toward increased FVs (+0.88, p=0.08) and decreased SSBs (-0.33, p=0.09). The adjusted difference between groups of 1.0 servings of FVs (p=0.13) and 0.35 servings of SSBs (p=0.25) indicated small to moderate effects of the intervention (Cohen's d=0.44 and -0.34, respectively). No differences were observed for screen time or BMI. A stand-alone mobile app may produce small to moderate effects for FVs and SSBs. Given the extensive reach of mobile devices, this pilot study demonstrates the need for larger-scale testing of similar programs to address obesity-related behaviors in high-risk youth. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  14. NASA's Corrosion Technology Laboratory at the Kennedy Space Center: Anticipating, Managing, and Preventing Corrosion

    Science.gov (United States)

    Calle, Luz Marina

    2014-01-01

    Corrosion is the degradation of a material that results from its interaction with the environment. The marine environment at NASAs Kennedy Space Center (KSC) has been documented by ASM International (formerly American Society for Metals) as the most corrosive in the United States. With the introduction of the Space Shuttle in 1981, the already highly corrosive conditions at the launch pads were rendered even more severe by the 70 tons of highly corrosive hydrochloric acid that were generated by the solid rocket boosters. Numerous failures at the launch pads are caused by corrosion.The structural integrity of ground infrastructure and flight hardware is critical to the success, safety, cost, and sustainability of space missions. As a result of fifty years of experience with launch and ground operations in a natural marine environment that is highly corrosive, NASAs Corrosion Technology Laboratory at KSC is a major source of corrosion control expertise in the launch and other environments. Throughout its history, the Laboratory has evolved from what started as an atmospheric exposure facility near NASAs launch pads into a world-wide recognized capability that provides technical innovations and engineering services in all areas of corrosion for NASA and external customers.This presentation will provide a historical overview of the role of NASAs Corrosion Technology in anticipating, managing, and preventing corrosion. One important challenge in managing and preventing corrosion involves the detrimental impact on humans and the environment of what have been very effective corrosion control strategies. This challenge has motivated the development of new corrosion control technologies that are more effective and environmentally friendly. Strategies for improved corrosion protection and durability can have a huge impact on the economic sustainability of human spaceflight operations.

  15. Bone phenotypes of P2 receptor knockout mice

    DEFF Research Database (Denmark)

    Orriss, Isabel; Syberg, Susanne; Wang, Ning

    2011-01-01

    The action of extracellular nucleotides is mediated by ionotropic P2X receptors and G-protein coupled P2Y receptors. The human genome contains 7 P2X and 8 P2Y receptor genes. Knockout mice strains are available for most of them. As their phenotypic analysis is progressing, bone abnormalities have...... been observed in an impressive number of these mice: distinct abnormalities in P2X7-/- mice, depending on the gene targeting construct and the genetic background, decreased bone mass in P2Y1-/- mice, increased bone mass in P2Y2-/- mice, decreased bone resorption in P2Y6-/- mice, decreased bone...... formation and bone resorption in P2Y13-/- mice. These findings demonstrate the unexpected importance of extracellular nucleotide signalling in the regulation of bone metabolism via multiple P2 receptors and distinct mechanisms involving both osteoblasts and osteoclasts....

  16. Pollution prevention/waste minimization program 1998 fiscal year work plan - WBS 1.11.2.1

    International Nuclear Information System (INIS)

    Howald, S.C.; Merry, D.S.

    1997-09-01

    Pollution Prevention/Waste Minimization (P2/WMin) is the Department of Energy's preferred approach to environmental management. The P2/WMin mission is to eliminate or minimize waste generation, pollutant releases to the environment, use of toxic substances, and to conserve resources by implementing cost-effective pollution prevention technologies, practices, and polices

  17. Prevention

    Science.gov (United States)

    ... Contact Aging & Health A to Z Find a Geriatrics Healthcare Professional Medications & Older Adults Making Your Wishes ... Prevention Hearing Loss Heart Attack High Blood Pressure Nutrition Osteoporosis Shingles Skin Cancer Related News Quitting Smoking, ...

  18. Identification of a New Morpholine Scaffold as a P2Y12 Receptor Antagonist

    Directory of Open Access Journals (Sweden)

    Young Ha Ahn

    2016-08-01

    Full Text Available The P2Y12 receptor is critical for platelet activation and is an attractive drug target for the prevention of atherothrombotic events. Despite the proven antithrombotic efficacy of P2Y12 inhibitors, these thienopyridine scaffolds are prodrugs that lack important features of the ideal antithrombotic agent. For this reason, ticagrelor—a new chemical class of P2Y12 receptor antagonist—was developed, but it can cause shortness of breath and various types of bleeding. Moreover, ticagrelor is a cytochrome P450 3A4 substrate/inhibitor and, therefore, caution should be exercised when it is used concomitantly with strong CYP3A4 inducers/inhibitors. There is a need for novel P2Y12 receptor antagonist scaffolds that are reversible and have high efficacy without associated side effects. Here, we describe a novel antagonist containing a morpholine moiety that was identified by screening libraries of commercially available compounds. The molecule, Compound E, acted on P2Y12, but not P2Y1 and P2Y13, and exhibited pharmacological characteristics that were distinct from those of ticagrelor, acting instead on P2Y12 via an allosteric mechanism. These results provide a basis for the development/optimization of a new class of P2Y12 antagonists.

  19. Information and communication technologies, a tool for risk prevention and accident management on sea ice

    Directory of Open Access Journals (Sweden)

    Elise Lépy

    2015-06-01

    Full Text Available Marine ice melting topic is a repetitive phenomenon in alarmist speeches on climate change. The present positive evolution of air temperatures has in all probability many impacts on the environment and more or less directly on societies. Face to the temperature elevation, the ice pack is undergone to an important temporal variability of ice growth and melting. Human populations can be exposed to meteorological and ice hazards engendering a societal risk. The purpose of this paper is to better understand how ICT get integrated into the risk question through the example of the Bay of Bothnia in the northern extremity of the Baltic Sea. The study deals with the way that Finnish society, advanced in the ICT field, faces to new technology use in risk prevention and accident management on sea ice.

  20. [Prevention and treatment for complications in the application of new technology for stomach cancers].

    Science.gov (United States)

    Su, Xiangqian; Zhou, Chuanyong; Yang, Hong

    2017-02-25

    With the rapid advancement of minimally invasive new technology, laparoscopic surgery and robotic surgery are now regarded as the main direction in surgical treatment for stomach cancers. Recent evidence has confirmed the safety and feasibility of laparoscopic surgery for early gastric cancer and advanced gastric cancer. However, gastrointestinal surgeons should pay more attention to complications after laparoscopic gastrectomy because of rich blood supply, complex tissue layers and lymph node metastasis. Common complications related to laparoscopic surgery are associated with laparoscopic instruments and operating, intra-abdominal bleeding, anastomotic leakage, anastomotic bleeding, pancreatic leakage, duodenal stump leakage, lymphatic leakage and so on. This article mainly focuses on the causes, prevention and treatment of the complications after laparoscopic gastrectomy.

  1. Application of Minicircle Technology of Self-Reproducing Synthetic Protein Drugs in Preventing Skin Allograft Rejection.

    Science.gov (United States)

    Lim, Sun Woo; Kim, Young Kyun; Park, Narae; Jin, Long; Jin, Jian; Doh, Kyoung Chan; Ju, Ji Hyeon; Yang, Chul Woo

    2015-07-30

    Recently, it has been reported that minicircle vectors could allow the expression of transgenes using the protein synthesis system of the host. Here, we tested a novel strategy to permit the production of synthetic biologics using minicircle technology and evaluated their feasibility as a therapeutic tool in a skin allograft model. We engineered vectors to carry cassette sequences for tocilizumab [anti-soluble interleukin-6 receptor (sIL-6R) antibody] and/or etanercept [tumor necrosis factor receptor 2 (TNFR2)-Fc fusion protein], and then isolated minicircle vectors from the parent vectors. We verified the production of proteins from minicircles and their duration in HEK293T cells and mice. We also evaluated whether these proteins were expressed at levels sufficient to ameliorate skin allograft rejection in mice. Each minicircle transfected into cells was detectable for at least 30 days. In mice, the drugs were mainly expressed in the liver and were detectable for at least 10 days after a single injection. These drugs were also detected in the blood. Treatment of mice with minicircles prolonged skin allograft survival, which was accompanied by a reduction of the number of interferon-γ+ or interleukin-17+ lymphocytes and an induction of forkhead box P3 expression. These findings suggest that blocking of sIL-6R and/or TNF-α using minicircles encoding tocilizumab and/or etanercept was functionally active and relevant for preventing acute allograft rejection. Self-reproducing synthetic protein drugs produced using minicircle technology are potentially powerful tools for preventing acute rejection in transplantation.

  2. Development of preventive maintenance and repair technology by laser for nuclear reactor devices

    International Nuclear Information System (INIS)

    Masataka, Tamura; Wataru, Kono; Syouhei, Kawano; Seiichiro, Kimura; Akira, Sudo; Hidenori, Takahashi; Seishi, Shima; Yuuichi, Motora

    2001-01-01

    As one of preventive maintenance technologies, Laser De-sensitization Treatment (LDT) was developed, which was realized by irradiating high power Nd:YAG laser onto the sensitized Heat Affected Zone (HAZ) surface. The LDT layer was formed both a molten layer of approximately 0.2 mm depth and a solution heat treatment layer. As mock-up test, the LDT process was applied in the vicinity of welding joints on the inside surface of pipes, and the tensile residual stress of outside surface of pipes was decreased. LDT processing on the inside surface of a pipe can be expected to prevent the occurrence of IGSCC owing to the phenomena of both metallurgical improvement and decrease of the residual stress on the outside surface of the pipe. The LDT processing was applied on the pipes of some actual nuclear power plants. As one of repair technologies at site in case that crack might occur, Under water Laser Seal Welding (ULSW) developed, in which welding layer isolates cracks from water in reactor in order to stop a growth of IGSCC cracks. This welding layer will be formed by means of feeding an appropriate welding wire at the position irradiating high power Nd:YAG laser. In experiments of bead on plate, laser power is fixed at 1 kw and welding speed is changed between 0.3 and 1.2 m/min. We investigated welding beads in the conditions that apparent heat input was between 0.5 and 2.0 kJ/cm. We confirmed that suitable welding condition range was more limited with lower apparent heat input. An artificial crack with opening width of 0.5 mm can be sealed by process of ULSW at 0.5 kJ/cm

  3. Facilitating Factors and Barriers to the Use of Emerging Technologies for Suicide Prevention in Europe: Multicountry Exploratory Study

    Science.gov (United States)

    Delgado, Carmen; Sánchez-Prada, Andrés; Parra-Vidales, Esther; de Leo, Diego; Franco-Martín, Manuel

    2018-01-01

    Background This study provides an analysis on the use of emerging technologies for the prevention of suicide in 8 different European countries. Objective The objective of this study was to analyze the potentiality of using emerging technologies in the area of suicide prevention based on the opinion of different professionals involved in suicide prevention. Methods Opinions of 3 groups of stakeholders (ie, relevant professionals in suicide field) were gathered using a specifically designed questionnaire to explore dimensions underlying perceptions of facilitating factors and barriers in relation to the use of emerging technologies for suicide prevention. Results Goal 1 involved facilitating factors for the use of emerging technologies in suicide prevention. Northern European countries, except for Belgium, attach greater relevance to those that optimize implementation and benefits. On the other hand, Southern European countries attach greater importance to professionally oriented and user-centered facilitating factors. According to different stakeholders, the analysis of these facilitating factors suggest that professionals in the field of social work attach greater relevance to those that optimize implementation and benefits. However, professionals involved in the area of mental health, policy makers, and political decision makers give greater importance to professionally oriented and user-centered facilitating factors. Goal 2 was related to barriers to the usability of emerging technologies for suicide prevention. Both countries and stakeholders attach greater importance to barriers associated with resource constraints than to those centered on personal limitations. There are no differences between countries or between stakeholders. Nevertheless, there is a certain stakeholders-countries interaction that indicates that the opinions on resource constraints expressed by different stakeholders do not follow a uniform pattern in different countries, but they differ

  4. Microbiological Surveillance and State of the Art Technological Strategies for the Prevention of Dialysis Water Pollution

    Directory of Open Access Journals (Sweden)

    Andrea Galfrè

    2012-08-01

    Full Text Available Methods: The present report attempts to illustrate the positive impact on the microbiological quality of dialysis patients over a 15-year period through the progressive implementation of state-of-the-art technological strategies and the optimization of microbiological surveillance procedures in five dialysis units in Sardinia. Results: Following on better microbiological, quality controls of dialysis water and improvement of procedures and equipment, a drastic improvement of microbiological water quality was observed in a total of 945 samples. The main aim was to introduce the use of microbiological culture methods as recommended by the most important guidelines. The microbiological results obtained have led to a progressive refining of controls and introduction of new materials and equipment, including two-stage osmosis and piping distribution rings featuring a greater capacity to prevent biofilm adhesion. The actions undertaken have resulted in unexpected quality improvements. Conclusions: Dialysis water should be viewed by the nephrologist as a medicinal product exerting a demonstrable positive impact on microinflammation in dialysis patients. A synergic effort between nephrologists and microbiologists undoubtedly constitutes the most effective means of preventing dialysis infections.

  5. Microbiological surveillance and state of the art technological strategies for the prevention of dialysis water pollution.

    Science.gov (United States)

    Bolasco, Piergiorgio; Contu, Antonio; Meloni, Patrizia; Vacca, Dorio; Galfrè, Andrea

    2012-08-01

    The present report attempts to illustrate the positive impact on the microbiological quality of dialysis patients over a 15-year period through the progressive implementation of state-of-the-art technological strategies and the optimization of microbiological surveillance procedures in five dialysis units in Sardinia. Following on better microbiological, quality controls of dialysis water and improvement of procedures and equipment, a drastic improvement of microbiological water quality was observed in a total of 945 samples. The main aim was to introduce the use of microbiological culture methods as recommended by the most important guidelines. The microbiological results obtained have led to a progressive refining of controls and introduction of new materials and equipment, including two-stage osmosis and piping distribution rings featuring a greater capacity to prevent biofilm adhesion. The actions undertaken have resulted in unexpected quality improvements. Dialysis water should be viewed by the nephrologist as a medicinal product exerting a demonstrable positive impact on microinflammation in dialysis patients. A synergic effort between nephrologists and microbiologists undoubtedly constitutes the most effective means of preventing dialysis infections.

  6. Pharmaceutical HIV prevention technologies in the UK: six domains for social science research.

    Science.gov (United States)

    Keogh, Peter; Dodds, Catherine

    2015-01-01

    The development of pharmaceutical HIV prevention technologies (PPTs) over the last five years has generated intense interest from a range of stakeholders. There are concerns that these clinical and pharmaceutical interventions are proceeding with insufficient input of the social sciences. Hence key questions around implementation and evaluation remain unexplored whilst biomedical HIV prevention remains insufficiently critiqued or theorised from sociological as well as other social science perspectives. This paper presents the results of an expert symposium held in the UK to explore and build consensus on the role of the social sciences in researching and evaluating PPTs in this context. The symposium brought together UK social scientists from a variety of backgrounds. A position paper was produced and distributed in advance of the symposium and revised in the light this consultation phase. These exchanges and the emerging structure of this paper formed the basis for symposium panel presentations and break-out sessions. Recordings of all sessions were used to further refine the document which was also redrafted in light of ongoing comments from symposium participants. Six domains of enquiry for the social sciences were identified and discussed: self, identity and personal narrative; intimacy, risk and sex; communities, resistance and activism; systems, structures and institutions; economic considerations and analyses; and evaluation and outcomes. These are discussed in depth alongside overarching consensus points for social science research in this area as it moves forward.

  7. Prevention

    DEFF Research Database (Denmark)

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation...... populations. These theories remain to be documented in proper, controlled and prospective studies. Breastfeeding and the late introduction of solid foods (>4 months) is associated with a reduced risk of food allergy, atopic dermatitis, and recurrent wheezing and asthma in early childhood. In all infants....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  8. Development and Field Application Experience of the Reactor Internal Preventive Maintenance Technology

    International Nuclear Information System (INIS)

    Kanno, A.; Yoshikubo, F.; Morinaka, R.; Tanaka, M.; Hasegawa, K.; Hatou, H.

    2012-01-01

    A reactor internal preventive maintenance technology, Water Jet Peening (WJP), has been developed as a stress corrosion cracking (SCC) mitigation technology that has been successfully implemented during refuelling outages at 15 Boiling Water Reactors (BWR) and three (3) Advanced BWRs (during the site construction and in the shop fabrication) in Japan. WJP is one of the most successful underwater peening methods, which utilizes the energy generated from the collapsing of bubbles produced by the cavitating water jet nozzle. The energy produced from the cavitations introduces compressive residual stress on the metal surface and subsurface up to a depth of several hundred micrometers. Most recently, we have successfully applied WJP to the bottom head components and to some cracked areas on the shroud support in the Tokai-2 plant. In the case of the bottom head components, we produced inspection and repair tooling as a contingency in the event SCC was identified and would be required to be repaired prior to the implementation of WJP. (author)

  9. Intravaginal rings as delivery systems for microbicides and multipurpose prevention technologies

    Directory of Open Access Journals (Sweden)

    Thurman AR

    2013-10-01

    Full Text Available Andrea Ries Thurman, Meredith R Clark, Jennifer Hurlburt, Gustavo F Doncel CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA Abstract: There is a renewed interest in delivering pharmaceutical products via intravaginal rings (IVRs. IVRs are flexible torus-shaped drug delivery systems that can be easily inserted and removed by the woman and that provide both sustained and controlled drug release, lasting for several weeks to several months. In terms of women's health care products, it has been established that IVRs effectively deliver contraceptive steroids and steroids for the treatment of postmenopausal vaginal atrophy. A novel application for IVRs is the delivery of antiretroviral drugs for the prevention of human immunodeficiency virus (HIV genital infection. Microbicides are antiviral drugs delivered topically for HIV prevention. Recent reviews of microbicide IVRs have focused on technologies in development and optimizing ring design. IVRs have several advantages, including the ability to deliver sustained drug doses for long periods of time while bypassing first pass metabolism in the gut. IVRs are discreet, woman-controlled, and do not require a trained provider for placement or fitting. Previous data support that women and their male sexual partners find IVRs highly acceptable. Multipurpose prevention technology (MPT products provide protection against unintended/mistimed pregnancy and reproductive tract infections, including HIV. Several MPT IVRs are currently in development. Early clinical testing of new microbicide and MPT IVRs will require a focus on safety, pharmacokinetics and pharmacodynamics. Specifically, IVRs will have to deliver tissue concentrations of drugs that are pharmacodynamically active, do not cause mucosal alterations or inflammation, and do not change the resident microbiota. The emergence of resistance to antiretrovirals will need to be investigated. IVRs should not

  10. Structural and Molecular Modeling Features of P2X Receptors

    Directory of Open Access Journals (Sweden)

    Luiz Anastacio Alves

    2014-03-01

    Full Text Available Currently, adenosine 5'-triphosphate (ATP is recognized as the extracellular messenger that acts through P2 receptors. P2 receptors are divided into two subtypes: P2Y metabotropic receptors and P2X ionotropic receptors, both of which are found in virtually all mammalian cell types studied. Due to the difficulty in studying membrane protein structures by X-ray crystallography or NMR techniques, there is little information about these structures available in the literature. Two structures of the P2X4 receptor in truncated form have been solved by crystallography. Molecular modeling has proven to be an excellent tool for studying ionotropic receptors. Recently, modeling studies carried out on P2X receptors have advanced our knowledge of the P2X receptor structure-function relationships. This review presents a brief history of ion channel structural studies and shows how modeling approaches can be used to address relevant questions about P2X receptors.

  11. The Promise of Multimedia Technology for STI/HIV Prevention: Frameworks for Understanding Improved Facilitator Delivery and Participant Learning

    Science.gov (United States)

    Epperson, Matthew W.; Gilbert, Louisa; Goddard, Dawn; Hunt, Timothy; Sarfo, Bright; El-Bassel, Nabila

    2018-01-01

    There is increasing excitement about multi-media sexually transmitted infection (STI) and HIV prevention interventions, yet there has been limited discussion of how use of multimedia technology may improve STI/HIV prevention efforts. The purpose of this paper is to describe the mechanisms through which multimedia technology may work to improve the delivery and uptake of intervention material. We present conceptual frameworks describing how multimedia technology may improve intervention delivery by increasing standardization and fidelity to the intervention material and the participant’s ability to learn by improving attention, cognition, emotional engagement, skills-building, and uptake of sensitive material about sexual and drug risks. In addition, we describe how the non-multimedia behavioral STI/HIV prevention intervention, Project WORTH, was adapted into a multimedia format for women involved in the criminal justice system and provide examples of how multimedia activities can more effectively target key mediators of behavioral change in this intervention. PMID:22223296

  12. The promise of multimedia technology for STI/HIV prevention: frameworks for understanding improved facilitator delivery and participant learning.

    Science.gov (United States)

    Khan, Maria R; Epperson, Matthew W; Gilbert, Louisa; Goddard, Dawn; Hunt, Timothy; Sarfo, Bright; El-Bassel, Nabila

    2012-10-01

    There is increasing excitement about multimedia sexually transmitted infection (STI) and HIV prevention interventions, yet there has been limited discussion of how use of multimedia technology may improve STI/HIV prevention efforts. The purpose of this paper is to describe the mechanisms through which multimedia technology may work to improve the delivery and uptake of intervention material. We present conceptual frameworks describing how multimedia technology may improve intervention delivery by increasing standardization and fidelity to the intervention material and the participant's ability to learn by improving attention, cognition, emotional engagement, skills-building, and uptake of sensitive material about sexual and drug risks. In addition, we describe how the non-multimedia behavioral STI/HIV prevention intervention, Project WORTH, was adapted into a multimedia format for women involved in the criminal justice system and provide examples of how multimedia activities can more effectively target key mediators of behavioral change in this intervention.

  13. The Impact of Information and Communication Technology on Internal Control’s Prevention and Detection of Fraud

    OpenAIRE

    Abiola, James

    2013-01-01

    This study explores the Impact of Information and Communication Technology (ICT) on internal control effectiveness in preventing and detecting fraud within the financial sector of a developing economy – Nigeria. Using a triangulation of questionnaire and interview techniques to investigate the internal control activities of Nigerian Internal Auditors in relation to their use of ICT in fraud prevention and detection, the study made use of cross-tabulations, correlation coefficients and one-way...

  14. Hypermethylation downregulates P2X7 receptor expression in astrocytoma

    OpenAIRE

    Liu, Jing; Li, Ningning; Sheng, Ruofan; Wang, Rui; Xu, Zude; Mao, Ying; Wang, Yin; Liu, Ying

    2017-01-01

    The present study investigated the altered expression of p2X purinoceptor (P2X7R) in astrocytoma. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to determine the P2X7R expression in glioblastoma (GBM) and surrounding normal brain tissue. DNA methylation levels of P2X7R gene promoter in GBM were analyzed using a Sequenom MassARRAY® System. Immunohistochemistry (IHC) was used to detect the expression of P2X7R in astrocytoma at different malignan...

  15. Two open states of P2X receptor channels

    Directory of Open Access Journals (Sweden)

    Milos B. Rokic

    2013-11-01

    Full Text Available The occupancy of the ATP binding sites of P2X receptor (P2XR channels causes the rapid opening of a small cation-permeable pore, followed by a gradual dilation that renders the pore permeable to large organic cations. Electrophysiologically, this phenomenon was shown using whole-cell current recording on P2X2R-, P2X2/X5R-, P2X4R- and P2X7R-expressing cells that were bathed in N-methyl-D-glucamine-containing buffers in the presence and/or absence of small monovalent and divalent cations. The pore dilation of P2X4R and P2X7R caused a secondary current growth, whereas that of P2X2R showed a sustained kinetic coupling of dilation and desensitization, leading to receptor channel closure. The pore size of the P2X7R open and dilated states was estimated to be approximately 0.85 nm and greater than 1 nm, respectively. The P2XR pore dilation was also observed in intact cells by measurement of fluorescent dye uptake/release, application of polyethylene glycols of different sizes, and atomic force microscopy. However, pore dilation was not observed at the single channel level. Structural data describing the dilated state are not available, and the relevance of orthosteric and allosteric ligand interactions to pore dilation was not studied.

  16. Lessons from reproductive health to inform multipurpose prevention technologies: don't reinvent the wheel.

    Science.gov (United States)

    Brady, Martha; Manning, Judy

    2013-12-01

    This paper presents the public health rationale for multipurpose prevention technologies (MPTs) for sexual and reproductive health (SRH) based on regional trends in demographic and SRH indicators. It then distils important lessons gleaned from the introduction of contraceptive and reproductive health products over the past several decades in order to inform the development and future introduction of MPTs for SRH. A comparison of current demographic and public health regional data clearly revealed that the greatest confluence of women's SRH concerns occurs in sub-Saharan Africa and South/West Asia. These regional overlaps of SRH risks and outcomes present a strong rationale for developing MPTs designed to simultaneously protect against unintended pregnancy, HIV and other STIs. Information from acceptability, marketing, and operations research on the female condom, emergency contraception, pills and intravaginal rings identified key product characteristics and socio-behavioral issues to be considered in the development and introduction of MPTs. Product characteristics such as formulation, duration of action, presence and magnitude of side effects, prescription status (over-the-counter vs. prescribed), provider type and training and user perspectives, all contributed in varying degrees to both provider and user bias, and subsequent uptake of these family planning methods. Underlying socio-behavioral issues, including risk perception, ambivalence, and social costs also contributed to demand and use. Early identification of target populations will be critical to market shaping, demand creation and defining appropriate service delivery channels for MPTs. Ultimately, knowledge, attitudes, perceptions and practices of users (and their partners) will drive the success- or failure- of product introduction. MPTs provide a compelling response to the multiple and reinforcing SRH risks faced by women in key regions of the world, but specific product characteristics and their

  17. P2X4: A fast and sensitive purinergic receptor

    Directory of Open Access Journals (Sweden)

    Jaanus Suurväli

    2017-10-01

    Full Text Available Extracellular nucleotides have been recognized as important mediators of activation, triggering multiple responses via plasma membrane receptors known as P2 receptors. P2 receptors comprise P2X ionotropic receptors and G protein-coupled P2Y receptors. P2X receptors are expressed in many tissues, where they are involved in a number of functions including synaptic transmission, muscle contraction, platelet aggregation, inflammation, macrophage activation, differentiation and proliferation, neuropathic and inflammatory pain. P2X4 is one of the most sensitive purinergic receptors (at nanomolar ATP concentrations, about one thousand times more than the archetypal P2X7. P2X4 is widely expressed in central and peripheral neurons, in microglia, and also found in various epithelial tissues and endothelial cells. It localizes on the plasma membrane, but also in intracellular compartments. P2X4 is preferentially localized in lysosomes, where it is protected from proteolysis by its glycosylation. High ATP concentration in the lysosomes does not activate P2X4 at low pH; P2X4 gets activated by intra-lysosomal ATP only in its fully dissociated tetra-anionic form, when the pH increases to 7.4. Thus, P2X4 is functioning as a Ca2+-channel after the fusion of late endosomes and lysosomes. P2X4 modulates major neurotransmitter systems and regulates alcohol-induced responses in microglia. P2X4 is one of the key receptors mediating neuropathic pain. However, injury-induced upregulation of P2X4 expression is gender dependent and plays a key role in pain difference between males and females. P2X4 is also involved in inflammation. Extracellular ATP being a pro-inflammatory molecule, P2X4 can trigger inflammation in response to high ATP release. It is therefore involved in multiple pathologies, like post-ischemic inflammation, rheumatoid arthritis, airways inflammation in asthma, neurodegenerative diseases and even metabolic syndrome. Although P2X4 remains poorly

  18. P2X1 receptors and the endothelium

    Directory of Open Access Journals (Sweden)

    LS Harrington

    2005-03-01

    Full Text Available Adenosine triphosphate (ATP is now established as a principle vaso-active mediator in the vasculature. Its actions on arteries are complex, and are mediated by the P2X and P2Y receptor families. It is generally accepted that ATP induces a bi-phasic response in arteries, inducing contraction via the P2X and P2Y receptors on the smooth muscle cells, and vasodilation via the actions of P2Y receptors located on the endothelium. However, a number of recent studies have placed P2X1 receptors on the endothelium of some arteries. The use of a specific P2X1 receptor ligand, a, b methylene ATP has demonstrated that P2X1 receptors also have a bi-functional role. The actions of ATP on P2X1 receptors is therefore dependant on its location, inducing contraction when located on the smooth muscle cells, and dilation when expressed on the endothelium, comparable to that of P2Y receptors.

  19. Purinergic P2 receptors as targets for novel analgesics.

    Science.gov (United States)

    Burnstock, Geoffrey

    2006-06-01

    Following hints in the early literature about adenosine 5'-triphosphate (ATP) injections producing pain, an ion-channel nucleotide receptor was cloned in 1995, P2X3 subtype, which was shown to be localized predominantly on small nociceptive sensory nerves. Since then, there has been an increasing number of papers exploring the role of P2X3 homomultimer and P2X2/3 heteromultimer receptors on sensory nerves in a wide range of organs, including skin, tongue, tooth pulp, intestine, bladder, and ureter that mediate the initiation of pain. Purinergic mechanosensory transduction has been proposed for visceral pain, where ATP released from epithelial cells lining the bladder, ureter, and intestine during distension acts on P2X3 and P2X2/3, and possibly P2Y, receptors on subepithelial sensory nerve fibers to send messages to the pain centers in the brain as well as initiating local reflexes. P1, P2X, and P2Y receptors also appear to be involved in nociceptive neural pathways in the spinal cord. P2X4 receptors on spinal microglia have been implicated in allodynia. The involvement of purinergic signaling in long-term neuropathic pain and inflammation as well as acute pain is discussed as well as the development of P2 receptor antagonists as novel analgesics.

  20. Development of Evaluation Technology for Prevention of Two-Phase FAC on Carbon Steel

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Mo; Shim, Heesang; Lee, Eun Hee; Hur, Do Haeng [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    There are many pipelines to be managed from wall thinning by flow accelerated corrosion (FAC) in the secondary system of a nuclear power. FAC is a process in which a normally protective oxide layer on the internal carbon or low-alloy steel piping surface dissolves into a stream of flowing water or a wet steam mixture. In this process, the oxide layer becomes thinner and the corrosion rate increases until the corrosion rate and dissolution rates are equal. Recent researches and reports indicate that the FAC problem is prevalent in spite of the development of an inspection method and management skills applying computer programs. Therefore, it is important to mitigate or prevent FAC on the carbon steel, and surface coating technology has been investigated for pipeline systems in a steam flow. Since the occurrence of a Surry-2 pipe rupture accident, a lot of effort has been made to manage the FAC of carbon steel piping. Some of the chemicals were known as a corrosion inhibitor. Bateman et al. reported that the addition of Ti may decrease the FAC rate of carbon steel by ∼ 65 %, TiO{sub 2} was also effective in mitigating the stress corrosion cracking of steam generator tubes under concentrated crevice conditions. A platinum doping method was applied as another mitigation strategy of carbon steel wall thinning. Noble metal, including Pt, had produced the layers of a very high catalyst concentration and this catalytic effect induced a lower corrosion potential for nickel alloys.

  1. Development of Evaluation Technology for Prevention of Two-Phase FAC on Carbon Steel

    International Nuclear Information System (INIS)

    Kim, Kyung Mo; Shim, Heesang; Lee, Eun Hee; Hur, Do Haeng

    2014-01-01

    There are many pipelines to be managed from wall thinning by flow accelerated corrosion (FAC) in the secondary system of a nuclear power. FAC is a process in which a normally protective oxide layer on the internal carbon or low-alloy steel piping surface dissolves into a stream of flowing water or a wet steam mixture. In this process, the oxide layer becomes thinner and the corrosion rate increases until the corrosion rate and dissolution rates are equal. Recent researches and reports indicate that the FAC problem is prevalent in spite of the development of an inspection method and management skills applying computer programs. Therefore, it is important to mitigate or prevent FAC on the carbon steel, and surface coating technology has been investigated for pipeline systems in a steam flow. Since the occurrence of a Surry-2 pipe rupture accident, a lot of effort has been made to manage the FAC of carbon steel piping. Some of the chemicals were known as a corrosion inhibitor. Bateman et al. reported that the addition of Ti may decrease the FAC rate of carbon steel by ∼ 65 %, TiO 2 was also effective in mitigating the stress corrosion cracking of steam generator tubes under concentrated crevice conditions. A platinum doping method was applied as another mitigation strategy of carbon steel wall thinning. Noble metal, including Pt, had produced the layers of a very high catalyst concentration and this catalytic effect induced a lower corrosion potential for nickel alloys

  2. B-Cure Laser Dental Pro technology for prevention and treatment of peri-implant mucositis

    Science.gov (United States)

    Gileva, O. S.; Libik, T. V.; Chuprakov, M. A.; Yakov, A. Y.; Mirsaeva, F. Z.

    2017-09-01

    Oral mucositis (OM) is the severe inflammation, lesioning and ulceration of the epithelia, accompanied by bleeding and intensive pain. OM is a common complication of dental implantation. Low-level laser therapy (LLLT) has been found to enhance the repair and healing of epithelia. The aim of this study was to evaluate the effectiveness of preventive and treatment use of LLLT (B-Cure Laser Dental Pro technology in original author's techniques) in the patients who have undergone dental implantation. Simple blind randomized prospective one-center comparative placebo-controlled clinical trial is carried out on the group of 30 partially edentulous patients. It is proved that the use of LLLT before and after installation of dental implants provides: 1) reliable reduction (by 3.5 times) of the frequency of implication and intensity of pain in the first days after operation; 2) reduction (by 3.3-3.7 times) of frequency, duration and intensity of local edematous and inflammatory processes in peri-implant zone and facial soft tissue edema; 3) effective prophylaxis of postoperative sensory, paresthesia and neurologic disturbances in maxillofacial area.

  3. Improving quality of fall prevention and management in elderly patients using information technology: The impact of computerized decision support

    NARCIS (Netherlands)

    Askari, M.

    2014-01-01

    This thesis explores the role of information technology (IT) for prevention and management of falls in both general practice and hospital settings. Specifically, we address the question of how disease management concepts, process modeling, prognostic models and computerized decision support systems

  4. US and Dutch nurse experiences with fall prevention technology within nursing home environment and workflow: a qualitative study

    NARCIS (Netherlands)

    Vandenberg, Ann E.; van Beijnum, Bernhard J.F.; Overdevest, Vera G.P.; Capezuti, Elizabeth; Johnson II, Theodore M.

    2017-01-01

    Falls remain a major geriatric problem, and the search for new solutions continues. We investigated how existing fall prevention technology was experienced within nursing home nurses' environment and workflow. Our NIH-funded study in an American nursing home was followed by a cultural learning

  5. Industrial pollution prevention programs in selected developing Asian countries

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, Shen-yann [Argonne National Lab., IL (United States)]|[East-West Center, Honolulu, HI (United States)

    1995-12-31

    This paper presents the information on current activities to promote industrial pollution prevention (P2) in five selected Asian economies including Hong Kong, Republic of Korea, the Philippines, ROC in Taiwan, and Thailand. These activities, generally initiated in the last 5 years, are classified into 6 categories: awareness promotion, education and training, information transfer, technology development an demonstration, technical assistance, and financial incentives. Although participation is voluntary, these programs are all important at the early stages of P2 promotion and should be useful in informing industries of the benefit of P2 and helping them identify specific P2 measures as viable environmental management alternatives.

  6. The role of the purinergic P2X7 receptor in inflammation

    Directory of Open Access Journals (Sweden)

    Rossi Adriano G

    2007-03-01

    Full Text Available Abstract The inflammatory process, orchestrated against a variety of injurious stimuli, is composed of three inter-related phases; initiation, propagation and resolution. Understanding the interplay between these three phases and harnessing the beneficial properties of inflammation whilst preventing its damaging effects, will undoubtedly lead to the advent of much needed therapies, particularly in chronic disease states. The P2X7 receptor (P2X7R is increasingly recognised as an important cell surface regulator of several key inflammatory molecules including IL-1β, IL-18, TNF-α and IL-6. Moreover, as P2X7R-dependent cytokine production is driven by activating the inflammasome, antagonists of this receptor are likely to have therapeutic potential as novel anti-inflammatory therapies. The function of the P2X7R in inflammation, immunity and its potential role in disease will be reviewed and discussed.

  7. Hyperglycemia-induced Renal P2X7 Receptor Activation Enhances Diabetes-related Injury

    Directory of Open Access Journals (Sweden)

    Robert I. Menzies

    2017-05-01

    Full Text Available Diabetes is a leading cause of renal disease. Glomerular mesangial expansion and fibrosis are hallmarks of diabetic nephropathy and this is thought to be promoted by infiltration of circulating macrophages. Monocyte chemoattractant protein-1 (MCP-1 has been shown to attract macrophages in kidney diseases. P2X7 receptors (P2X7R are highly expressed on macrophages and are essential components of pro-inflammatory signaling in multiple tissues. Here we show that in diabetic patients, renal P2X7R expression is associated with severe mesangial expansion, impaired glomerular filtration (≤40 ml/min/1.73 sq. m., and increased interstitial fibrosis. P2X7R activation enhanced the release of MCP-1 in human mesangial cells cultured under high glucose conditions. In mice, P2X7R-deficiency prevented glomerular macrophage attraction and collagen IV deposition; however, the more severe interstitial inflammation and fibrosis often seen in human diabetic kidney diseases was not modelled. Finally, we demonstrate that a P2X7R inhibitor (AZ11657312 can reduce renal macrophage accrual following the establishment of hyperglycemia in a model of diabetic nephropathy. Collectively these data suggest that P2X7R activation may contribute to the high prevalence of kidney disease found in diabetics.

  8. Cryptocurrency Networks: A New P2P Paradigm

    Directory of Open Access Journals (Sweden)

    Sergi Delgado-Segura

    2018-01-01

    Full Text Available P2P networks are the mechanism used by cryptocurrencies to disseminate system information while keeping the whole system as much decentralized as possible. Cryptocurrency P2P networks have new characteristics that propose new challenges and avoid some problems of existing P2P networks. By characterizing the most relevant cryptocurrency network, Bitcoin, we provide details on different properties of cryptocurrency networks and their similarities and differences with standard P2P network paradigms. Our study allows us to conclude that cryptocurrency networks present a new paradigm of P2P networks due to the mechanisms they use to achieve high resilience and security. With this new paradigm, interesting research lines can be further developed, both in the focused field of P2P cryptocurrency networks and also when such networks are combined with other distributed scenarios.

  9. (p,2p) experiments at the University of Maryland cyclotron

    International Nuclear Information System (INIS)

    Roos, P.G.

    1976-11-01

    Some of the (p,2p) work which has been carried out at the Maryland Cyclotron is discussed. A brief introduction to the (p,2p) reaction is presented, and the types of experimental techniques utilized in (p,2p) studies are discussed. A brief introduction is given to the various theoretical treatments presently available to analyze (p,2p) reaction data. Secondly, experimental and theoretical studies of (p,2p) on d, 3 He, and 4 He carried out by the Maryland group are presented. Thirdly, (p,2p) results are discussed for 6 Li, 7 Li, and 12 C at 100 MeV. Fourthly, the effects of distortion on the experimental data are considered by presenting theoretical calculations for 12 C and 40 Ca at various bombarding energies

  10. Analysis of industrial pollution prevention programs in selected Asian countries

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, S.Y. [Argonne National Lab., IL (United States). Environmental Assessment Div.]|[East-West Center, Honolulu, HI (United States)

    1995-05-01

    Industrialization in developing countries is causing increasing environmental damage. Pollution prevention (P2) is an emerging environmental concept that could help developing countries achieve leapfrog goals, bypassing old and pollutive technologies and minimizing traditional control practices. The current P2 promotion activities in Hong Kong, the Republic of Korea, the Philippines, Singapore, Taiwan, and Thailand are discussed. These programs, generally initiated in the last 5 years, are classified into five categories: awareness promotion, education and training, information transfer, technical assistance, and financial incentives. All important at the early stages of P2 promotion, these programs should inform industries of the benefits of P2 and help them identify applicable P2 measures. Participation in these programs is voluntary. The limited data indicate that adoption of P2 measures in these countries is not yet widespread. Recommendations for expanding P2 promotion activities include (1) strengthening the design and enforcement of environmental regulations; (2) providing P2 training and education to government workers, nongovernmental organizations and labor unions officials, university faculties, and news media; (3) tracking the progress of P2 programs; (4) implementing selected P2 mandatory measures; (5) identifying cleaner production technologies for use in new facilities; (6) implementing special programs for small and medium enterprises; and (7) expanding P2 promotion to other sectors, such as agriculture and transportation, and encouraging green design and green consumerism.

  11. Information Technology: The Preventive Health Care Application and an Associated Upgrade

    National Research Council Canada - National Science Library

    2002-01-01

    The Preventive Health Care Application was a tool designed to enable clinicians to deliver and track appropriate and timely preventive services provided to all enrolled military health system members...

  12. Data transport and management in P2P Data Management in Mobile Wireless Sensor Network

    International Nuclear Information System (INIS)

    Sahar, S.; Shaikh, F.K.

    2013-01-01

    The rapid growth in wireless technologies has made wireless communication an important source for transporting data across different domains. In the same way, there are possibilities of many potential applications that can be deployed using WSNs (Wireless Sensor Networks). However, very limited applications are deployed in real life due to the uncertainty and dynamics of the environment and scare resources. This makes data management in WSN a challenging area to find an approach that suits its characteristics. Currently, the trend is to find efficient data management schemes using evolving technologies, i.e. P2P (Peer-to-Peer) systems. Many P2P approaches have been applied in WSNs to carry out the data management due to similarities between WSN and P2P. With the similarities, there are differences too that makes P2P protocols inefficient in WSNs. Furthermore, to increase the efficiency and to exploit the delay tolerant nature of WSNs, where ever possible, the mobile WSNs are gaining importance. Thus, creating a three dimensional problem space to consider, i.e. mobility, WSNs and P2P. In this paper, an efficient algorithm is proposed for data management using P2P techniques for mobile WSNs. The real world implementation and deployment of proposed algorithm is also presented. (author)

  13. Bandwidth Reduction via Localized Peer-to-Peer (P2P Video

    Directory of Open Access Journals (Sweden)

    Ken Kerpez

    2010-01-01

    Full Text Available This paper presents recent research into P2P distribution of video that can be highly localized, preferably sharing content among users on the same access network and Central Office (CO. Models of video demand and localized P2P serving areas are presented. Detailed simulations of passive optical networks (PON are run, and these generate statistics of P2P video localization. Next-Generation PON (NG-PON is shown to fully enable P2P video localization, but the lower rates of Gigabit-PON (GPON restrict performance. Results here show that nearly all of the traffic volume of unicast video could be delivered via localized P2P. Strong growth in video delivery via localized P2P could lower overall future aggregation and core network bandwidth of IP video traffic by 58.2%, and total consumer Internet traffic by 43.5%. This assumes aggressive adoption of technologies and business practices that enable highly localized P2P video.

  14. P2X7 Receptors in Neurological and Cardiovascular Disorders

    Directory of Open Access Journals (Sweden)

    Stephen D. Skaper

    2009-01-01

    Full Text Available P2X receptors are ATP-gated cation channels that mediate fast excitatory transmission in diverse regions of the brain and spinal cord. Several P2X receptor subtypes, including P2X7, have the unusual property of changing their ion selectivity during prolonged exposure to ATP, which results in a channel pore permeable to molecules as large as 900 daltons. The P2X7 receptor was originally described in cells of hematopoietic origin, and mediates the influx of Ca2+ and Na+ and Ca2+ and Na+ ions as well as the release of proinflammatory cytokines. P2X7 receptors may affect neuronal cell death through their ability to regulate the processing and release of interleukin-1, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7 receptors provides an inflammatory stimulus, and P2X7 receptor-deficient mice have substantially attenuated inflammatory responses, including models of neuropathic and chronic inflammatory pain. Moreover, P2X7 receptor activity, by regulating the release of proinflammatory cytokines, may be involved in the pathophysiology of depression. Apoptotic cell death occurs in a number of vascular diseases, including atherosclerosis, restenosis, and hypertension, and may be linked to the release of ATP from endothelial cells, P2X7 receptor activation, proinflammatory cytokine production, and endothelial cell apoptosis. In this context, the P2X7 receptor may be viewed as a gateway of communication between the nervous, immune, and cardiovascular systems.

  15. The role of P2X receptors in bone biology

    DEFF Research Database (Denmark)

    Jørgensen, N R; Syberg, S; Ellegaard, M

    2015-01-01

    come from studies on murine knockout models and from pharmacologic studies on cells and animals. More recently, the role of P2X receptors in human bone diseases has been documented. Loss-of-functions polymorphisms in the P2X7 receptorare associated with bone loss and increased fracture risk. Very...

  16. A Meta-Analysis of the Impact of Universal and Indicated Preventive Technology-Delivered Interventions for Higher Education Students.

    Science.gov (United States)

    Conley, Colleen S; Durlak, Joseph A; Shapiro, Jenna B; Kirsch, Alexandra C; Zahniser, Evan

    2016-08-01

    The uses of technology-delivered mental health treatment options, such as interventions delivered via computer, smart phone, or other communication or information devices, as opposed to primarily face-to-face interventions, are proliferating. However, the literature is unclear about their effectiveness as preventive interventions for higher education students, a population for whom technology-delivered interventions (TDIs) might be particularly fitting and beneficial. This meta-analytic review examines technological mental health prevention programs targeting higher education students either without any presenting problems (universal prevention) or with mild to moderate subclinical problems (indicated prevention). A systematic literature search identified 22 universal and 26 indicated controlled interventions, both published and unpublished, involving 4763 college, graduate, or professional students. As hypothesized, the overall mean effect sizes (ESs) for both universal (0.19) and indicated interventions (0.37) were statistically significant and differed significantly from each other favoring indicated interventions. Skill-training interventions, both universal (0.21) and indicated (0.31), were significant, whereas non-skill-training interventions were only significant among indicated (0.25) programs. For indicated interventions, better outcomes were obtained in those cases in which participants had access to support during the course of the intervention, either in person or through technology (e.g., email, online contact). The positive findings for both universal and indicated prevention are qualified by limitations of the current literature. To improve experimental rigor, future research should provide detailed information on the level of achieved implementation, describe participant characteristics and intervention content, explore the impact of potential moderators and mechanisms of success, collect post-intervention and follow-up data regardless of

  17. Binary phosphates NaLnP2O7

    International Nuclear Information System (INIS)

    Anisimova, N.Yu.; Trunov, V.K.; Chudinova, N.N.

    1988-01-01

    The results of synthesis and identification of compounds of the NaLnP 2 O 7 (Ln=La,...Lu) composition are presented. 14 compounds of the above composition referring to two structural types are prepared and characterized. The data on NaLnP 2 O 7 synthesis in the Na 2 O-Ln:2O 3 -P 2 O 5 system are given. Binary phosphates of the NaLnP 2 O 7 -type (Ln=La,...Lu) are separated and identified in the subsolidus part of the Na 2 O-Ln 2 O 3 -P 2 O 5 system. Their crystallochemical parameters are determined and the presence of two structural types in the La-Lu series is shown. Thermal stability of binary phosphates is studied

  18. Self-management support interventions that are clinically linked and technology enabled: can they successfully prevent and treat diabetes?

    Science.gov (United States)

    Kaufman, Neal D; Woodley, Paula D Patnoe

    2011-05-01

    Patients with diabetes need a complex set of services and supports. The challenge of integrating these services into the diabetes regimen can be successfully overcome through self-management support interventions that are clinically linked and technology enabled: self-management support because patients need help mastering the knowledge, attitudes, skills, and behaviors so necessary for good outcomes; interventions because comprehensive theory-based, evidence-proven, long-term, longitudinal interventions work better than direct-to-consumer or nonplanned health promotion approaches; clinically linked because patients are more likely to adopt new behaviors when the approach is in the context of a trusted therapeutic relationship and within an effective medical care system; and technology enabled because capitalizing on the amazing power of information technology leads to the delivery of cost-effective, scalable, engaging solutions that prevent and manage diabetes. © 2011 Diabetes Technology Society.

  19. Integration of advances in social media and mHealth technology are pivotal to successful cancer prevention and control.

    Science.gov (United States)

    O'Leary, D Peter; Zaheer, Amir; Redmond, H Paul; Corrigan, Mark A

    2016-01-01

    The successful prevention and treatment of cancer is dependent upon efficient and reliable communication between healthcare workers and patients. Advances in social media and mHealth platforms have provided new ways in which to enhance the sharing of cancer related information. Other benefits of embracing this technology include utilising its analytic capabilities which can process the vast quantity of information generated from genome exploration in a highly efficient manner. The aim of this review is to provide an overview of the rapidly evolving areas through which digital engagement is proving useful in the prevention and control of cancer.

  20. EPA-developed, patented technologies related to pollution prevention that are available for licensing.

    Science.gov (United States)

    Under the Federal Technology Transfer Act (FTTA), Federal Agencies can patent inventions developed during the course of research. These technologies can then be licensed to businesses or individuals for further development and sale in the marketplace. These technologies primarily relate to contaminant removal in the environment.

  1. P2X-Receptor Antagonists Inhibit the Interaction of S. aureus Hemolysin A with Membranes

    Directory of Open Access Journals (Sweden)

    Markus Schwiering

    2017-10-01

    Full Text Available The pore forming hemolysin A, Hla, is a major virulence factor of Staphylococcus aureus. Apparently, 1–2 pore(s per cell suffice(s to cause cell death. Accumulated experimental evidence points towards a major role of ATP-gated purinergic receptors (P2XR for hemolysis caused by Hla, complement and other pore forming proteins, presumably by increasing membrane permeability. Indeed, in experiments employing rabbit erythrocytes, inhibitory concentrations of frequently employed P2XR-antagonists were in a similar range as previously reported for erythrocytes of other species and other toxins. However, Hla-dependent hemolysis was not enhanced by extracellular ATP, and oxidized adenosinetriphosphate (oxATP had only a minor inhibitory effect. Unexpectedly, P2XR-inhibitors also prevented Hla-induced lysis of pure lipid membranes, demonstrating that the inhibition did not even depend on the presence of P2XR. Fluorescence microscopy and gel-electrophoresis clearly revealed that P2XR-inhibitors interfere with binding and subsequent oligomerisation of Hla with membranes. Similar results were obtained employing HaCaT-cells. Furthermore, calorimetric data and hemolysis experiments with Hla pre-treated with pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS showed that this compound directly binds to Hla. Our results call for a critical re-assessment of the appealing concept, which suggests that P2XR are general amplifiers of damage by pore-forming proteins.

  2. E2E blocking probability of IPTV and P2PTV

    NARCIS (Netherlands)

    Lu, Y.; Kuipers, F.; Janic, M.; Mieghem, P. van

    2008-01-01

    Increased Internet speeds together with new possibilities for tailor-made television services have spurred the interest in providing television via the Internet. Several television services are readily available and both IP-layer and application-layer (P2P) technologies are used. When disregarding

  3. Purinergní P2X rodina a specifické vlastnosti P2X7 podtypu

    Czech Academy of Sciences Publication Activity Database

    Jindřichová, Marie; Zemková, Hana

    2013-01-01

    Roč. 62, č. 2 (2013), s. 40-46 ISSN 1210-6313 R&D Projects: GA ČR(CZ) GPP304/12/P371 Institutional support: RVO:67985823 Keywords : extracellular ATP * purinergic P2X family * P2X7 receptor * cell proliferation and apoptosis Subject RIV: ED - Physiology

  4. P2MP MPLS-Based Hierarchical Service Management System

    Science.gov (United States)

    Kumaki, Kenji; Nakagawa, Ikuo; Nagami, Kenichi; Ogishi, Tomohiko; Ano, Shigehiro

    This paper proposes a point-to-multipoint (P2MP) Multi-Protocol Label Switching (MPLS) based hierarchical service management system. Traditionally, general management systems deployed in some service providers control MPLS Label Switched Paths (LSPs) (e.g., RSVP-TE and LDP) and services (e.g., L2VPN, L3VPN and IP) separately. In order for dedicated management systems for MPLS LSPs and services to cooperate with each other automatically, a hierarchical service management system has been proposed with the main focus on point-to-point (P2P) TE LSPs in MPLS path management. In the case where P2MP TE LSPs and services are deployed in MPLS networks, the dedicated management systems for P2MP TE LSPs and services must work together automatically. Therefore, this paper proposes a new algorithm that uses a correlation between P2MP TE LSPs and multicast VPN services based on a P2MP MPLS-based hierarchical service management architecture. Also, the capacity and performance of the proposed algorithm are evaluated by simulations, which are actually based on certain real MPLS production networks, and are compared to that of the algorithm for P2P TE LSPs. Results show this system is very scalable within real MPLS production networks. This system, with the automatic correlation, appears to be deployable in real MPLS production networks.

  5. From Client-Server to P2P Networking

    Science.gov (United States)

    Liu, Lu; Antonopoulos, Nick

    Peer-to-peer (P2P) networks attract attentions worldwide with their great success in file sharing networks (such as Napster, Gnutella, Freenet, BitTorrent, Kazaa, and JXTA). An explosive increase in the popularity of P2P networks has been witnessed by millions of Internet users. In this chapter, an investigation of network architecture evolution, from client-server to P2P networking, will be given, underlining the benefits and the potential problems of existing approaches, which provides essential theoretical base to drive future generation of distributed systems.

  6. PPADS: an antagonist at endothelial P2Y-purinoceptors but not P2U-purinoceptors.

    Science.gov (United States)

    Brown, C; Tanna, B; Boarder, M R

    1995-11-01

    1. Bovine aortic endothelial (BAE) cells contain two co-existing receptors for extracellular ATP, the P2Y and P2U-purinoceptors. Here we have determined whether the proposed P2X-purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2', 4'-disulphonic acid (PPADS) could distinguish between these two receptor subtypes. 2. Cells labelled with myo-[2-3H]-inositol were stimulated with increasing concentrations of either the P2Y-agonist, 2MeSATP, or the P2U-agonist, UTP in the absence or presence of 30 microM PPADS. The accumulation of total [3H]-inositol (poly)phosphates mediated by 2MeSATP was markedly attenuated by PPADS, whereas the response to UTP was not significantly affected. 3. Stimulation of BAE cells with increasing concentrations of ATP showed a reduced response in the presence of 10 microM PPADS, but this effect of the antagonist was not significant. By contrast, inhibition of the response to ADP was profound and highly significant. 4. These observations show that PPADS is not a selective P2X-purinoceptor antagonist, but is able to distinguish between P2Y- and P2YU-purinoceptors in BAE cells, and indicate that this compound may provide a useful tool in the study of multiple subtypes of P2-purinoceptors. Furthermore the results are consistent with the hypothesis that ATP interacts with both receptor subtypes, but that the action of ADP is primarily at the P2Y-purinoceptor in these endothelial cells.

  7. Results of FE65-P2 Pixel Readout Test Chip for High Luminosity LHC Upgrades

    CERN Document Server

    AUTHOR|(SzGeCERN)394193

    2016-01-01

    A pixel readout test chip called FE65-P2 has been fabricated on 65 nm CMOS technology. FE65-P2 contains a matrix of 64 x 64 pixels on 50 micron by 50 micron pitch, designed to read out a bump bonded sensor. The goals of FE65-P2 are to demonstrate excellent analog performance isolated from digital activity well enough to achieve 500 electron stable threshold, be radiation hard to at least 500 Mrad, and prove the novel concept of isolated analog front ends embedded in a flat digital design, dubbed “analog islands in a digital sea”. Experience from FE65-P2 and hybrid assemblies will be applied to the design for a large format readout chip, called RD53A, to be produced in a wafer run in early 2017 by the RD53 collaboration. We review the case for 65 nm technology and report on threshold stability test results for the FE65-P2.

  8. The role of P2X receptors in bone biology

    DEFF Research Database (Denmark)

    Jørgensen, N R; Syberg, S; Ellegaard, M

    2015-01-01

    Bone is a highly dynamic organ, being constantly modeled and remodeled in order to adapt to the changing need throughout life. Bone turnover involves the coordinated actions of bone formation and bone degradation. Over the past decade great effort has been put into the examination of how P2X...... receptors regulate bone metabolism and especially for the P2X7 receptor an impressive amount of evidence has now documented its expression in osteoblasts, osteoclasts, and osteocytes as well as important functional roles in proliferation, differentiation, and function of the cells of bone. Key evidence has...... come from studies on murine knockout models and from pharmacologic studies on cells and animals. More recently, the role of P2X receptors in human bone diseases has been documented. Loss-of-functions polymorphisms in the P2X7 receptorare associated with bone loss and increased fracture risk. Very...

  9. [Digital Pen & Paper® technology to manage clinical risk and to prevent medical malpractice claims].

    Science.gov (United States)

    Genovese, Umberto; Del Sordo, Sara; Gerosa, Camillo; Mobilia, Francesca; Raineri, Massimo

    2014-01-01

    The use of innovative technologies in the health sector can be a key element in clinical risk management. In order to reduce errors in medical recording and to provide medico-legal evidence, Digital Pen & Paper technology has been adopted by medical staff of a hospital in Milan. The Authors introduce the first results of this trial: notable advantages have been reported in compilation, transmission and storage of medical records. Furthermore, this technology could provide evidence in evaluating medical malpractice claims.

  10. Tetravalent one-regular graphs of order 4p2

    DEFF Research Database (Denmark)

    Feng, Yan-Quan; Kutnar, Klavdija; Marusic, Dragan

    2014-01-01

    A graph is one-regular if its automorphism group acts regularly on the set of its arcs. In this paper tetravalent one-regular graphs of order 4p2, where p is a prime, are classified.......A graph is one-regular if its automorphism group acts regularly on the set of its arcs. In this paper tetravalent one-regular graphs of order 4p2, where p is a prime, are classified....

  11. The role of P2X receptors in bone biology.

    Science.gov (United States)

    Jørgensen, N R; Syberg, S; Ellegaard, M

    2015-01-01

    Bone is a highly dynamic organ, being constantly modeled and remodeled in order to adapt to the changing need throughout life. Bone turnover involves the coordinated actions of bone formation and bone degradation. Over the past decade great effort has been put into the examination of how P2X receptors regulate bone metabolism and especially for the P2X7 receptor an impressive amount of evidence has now documented its expression in osteoblasts, osteoclasts, and osteocytes as well as important functional roles in proliferation, differentiation, and function of the cells of bone. Key evidence has come from studies on murine knockout models and from pharmacologic studies on cells and animals. More recently, the role of P2X receptors in human bone diseases has been documented. Loss-of-functions polymorphisms in the P2X7 receptorare associated with bone loss and increased fracture risk. Very recently a report from a genetic study in multiple myeloma demonstrated that decreased P2X7 receptor function was associated with increased risk of developing multiple myeloma. In contrast, the risk of developing myeloma bone disease and subsequent vertebral fractures was increased in subjects carrying P2X7 receptor gain-of-function alleles as compared to subjects only carrying loss-of-function or normal functioning alleles. It is evident that P2X receptors are important in regulating bone turnover and maintaining bone mass, and thereby holding great potential as novel drug targets for treatment of bone diseases. However, further research is needed before we fully understand the roles and effects of P2X receptors in bone.

  12. Meeting of the ITER SWG-P2 in Vienna

    International Nuclear Information System (INIS)

    Pinkau, K.; Kishimoto, H.

    1999-01-01

    The Special Working Group established under Protocol 2 to the ITER IDA Agreement (SWG-P2) met at the IAEA in Vienna in 6-9 December 1999. This report contains excerpts from the report of the ITER SWG-P2 to the ITER Council on the Joint Implementation of ITER, detailing benefits, contributions, the legal framework, siting, licensing and decommissioning as well as procurement, staffing and intellectual property rights

  13. microRNA targeting of the P2X7 purinoceptor opposes a contralateral epileptogenic focus in the hippocampus.

    Science.gov (United States)

    Jimenez-Mateos, Eva M; Arribas-Blazquez, Marina; Sanz-Rodriguez, Amaya; Concannon, Caoimhin; Olivos-Ore, Luis A; Reschke, Cristina R; Mooney, Claire M; Mooney, Catherine; Lugara, Eleonora; Morgan, James; Langa, Elena; Jimenez-Pacheco, Alba; Silva, Luiz Fernando Almeida; Mesuret, Guillaume; Boison, Detlev; Miras-Portugal, M Teresa; Letavic, Michael; Artalejo, Antonio R; Bhattacharya, Anindya; Diaz-Hernandez, Miguel; Henshall, David C; Engel, Tobias

    2015-12-03

    The ATP-gated ionotropic P2X7 receptor (P2X7R) modulates glial activation, cytokine production and neurotransmitter release following brain injury. Levels of the P2X7R are increased in experimental and human epilepsy but the mechanisms controlling P2X7R expression remain poorly understood. Here we investigated P2X7R responses after focal-onset status epilepticus in mice, comparing changes in the damaged, ipsilateral hippocampus to the spared, contralateral hippocampus. P2X7R-gated inward currents were suppressed in the contralateral hippocampus and P2rx7 mRNA was selectively uploaded into the RNA-induced silencing complex (RISC), suggesting microRNA targeting. Analysis of RISC-loaded microRNAs using a high-throughput platform, as well as functional assays, suggested the P2X7R is a target of microRNA-22. Inhibition of microRNA-22 increased P2X7R expression and cytokine levels in the contralateral hippocampus after status epilepticus and resulted in more frequent spontaneous seizures in mice. The major pro-inflammatory and hyperexcitability effects of microRNA-22 silencing were prevented in P2rx7(-/-) mice or by treatment with a specific P2X7R antagonist. Finally, in vivo injection of microRNA-22 mimics transiently suppressed spontaneous seizures in mice. The present study supports a role for post-transcriptional regulation of the P2X7R and suggests therapeutic targeting of microRNA-22 may prevent inflammation and development of a secondary epileptogenic focus in the brain.

  14. Accelerated FoxP2 Evolution in Echolocating Bats

    Science.gov (United States)

    Li, Gang; Wang, Jinhong; Rossiter, Stephen J.; Jones, Gareth; Zhang, Shuyi

    2007-01-01

    FOXP2 is a transcription factor implicated in the development and neural control of orofacial coordination, particularly with respect to vocalisation. Observations that orthologues show almost no variation across vertebrates yet differ by two amino acids between humans and chimpanzees have led to speculation that recent evolutionary changes might relate to the emergence of language. Echolocating bats face especially challenging sensorimotor demands, using vocal signals for orientation and often for prey capture. To determine whether mutations in the FoxP2 gene could be associated with echolocation, we sequenced FoxP2 from echolocating and non-echolocating bats as well as a range of other mammal species. We found that contrary to previous reports, FoxP2 is not highly conserved across all nonhuman mammals but is extremely diverse in echolocating bats. We detected divergent selection (a change in selective pressure) at FoxP2 between bats with contrasting sonar systems, suggesting the intriguing possibility of a role for FoxP2 in the evolution and development of echolocation. We speculate that observed accelerated evolution of FoxP2 in bats supports a previously proposed function in sensorimotor coordination. PMID:17878935

  15. Accelerated FoxP2 evolution in echolocating bats.

    Directory of Open Access Journals (Sweden)

    Gang Li

    Full Text Available FOXP2 is a transcription factor implicated in the development and neural control of orofacial coordination, particularly with respect to vocalisation. Observations that orthologues show almost no variation across vertebrates yet differ by two amino acids between humans and chimpanzees have led to speculation that recent evolutionary changes might relate to the emergence of language. Echolocating bats face especially challenging sensorimotor demands, using vocal signals for orientation and often for prey capture. To determine whether mutations in the FoxP2 gene could be associated with echolocation, we sequenced FoxP2 from echolocating and non-echolocating bats as well as a range of other mammal species. We found that contrary to previous reports, FoxP2 is not highly conserved across all nonhuman mammals but is extremely diverse in echolocating bats. We detected divergent selection (a change in selective pressure at FoxP2 between bats with contrasting sonar systems, suggesting the intriguing possibility of a role for FoxP2 in the evolution and development of echolocation. We speculate that observed accelerated evolution of FoxP2 in bats supports a previously proposed function in sensorimotor coordination.

  16. Evaluation of effectiveness of SCC prevention technologies after long term operation at the 'Fugen' Power Station

    International Nuclear Information System (INIS)

    Yuasa, Toyotaka; Abe, Teruyoshi; Nakamura, Takahisa; Myochin, Munetaka; Takagi, Hisatsugu

    2014-01-01

    Suffered SCC (stress corrosion cracking) at the primary cooling system in 1980, the 'Fugen' power station introduced the three preventive technologies immediately. After the upgrade of the plant, no SCC occurred during the operation period. We have inspected the actual structural materials of the 'Fugen' power station on its decommissioning stage to evaluate effectiveness of SCC management technologies, which are combining material replacement, induction heating stress improvement (IHSI) to reduce the welding residual tensile stress, and application of hydrogen addition to reduce oxygen in the water. No crack in the materials was found by metallurgical structure observation. Moreover, judging from the analysis of residual stress and the heat affected zone in the materials, the effectiveness of SCC management technologies was verified. (author)

  17. Innovative Capping Technology To Prevent The Migration of Toxic Chemicals From Contaminated Sediments

    Science.gov (United States)

    Capping is a common strategy for decreasing the risk associated with contaminated sediments in lakes and streams. Historically, caps have been designed to physically isolate contaminated sediments and prevent the transport of contaminants from sediments into the water above them...

  18. The role of mobile phone technology in understanding and preventing suicidal behavior.

    NARCIS (Netherlands)

    Beurs, D. de; Kirtley, O.; Kerkhof, A.; Portzky, G.; O'Connor, R.C.

    2015-01-01

    In this editorial, we discuss how mobile phone technology has the potential to move the field forward in terms of understanding suicide risk as well as laying foundations for the development of effective treatments/interventions. We have focused on mobile health technology given the rapid growth of

  19. Unique crystallization behavior of sodium manganese pyrophosphate Na2MnP2O7 glass and its electrochemical properties

    Directory of Open Access Journals (Sweden)

    Morito Tanabe

    2017-06-01

    Full Text Available Crystallization behavior of Na2MnP2O7 precursor glass was examined. Layered type Na2MnP2O7 was formed at 461 °C for 3 h in N2 filled electric furnace. Irreversible phase change was confirmed from layered Na2MnP2O7 to β-Na2MnP2O7 over 600 °C. At 650 °C crystallized phase was completely changed to β-phase. By means of charge and discharge testing it is found that layered Na2MnP2O7 is also active as cathode in sodium ion batteries. We found glass-ceramics technology is one of the suitable process for the synthesis of layered Na2MnP2O7 cathode without any complicate process.

  20. P2X7 Receptor Activation Modulates Autophagy in SOD1-G93A Mouse Microglia

    Directory of Open Access Journals (Sweden)

    Paola Fabbrizio

    2017-08-01

    Full Text Available Autophagy and inflammation play determinant roles in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS, an adult-onset neurodegenerative disease characterized by deterioration and final loss of upper and lower motor neurons (MN priming microglia to sustain neuroinflammation and a vicious cycle of neurodegeneration. Given that extracellular ATP through P2X7 receptor constitutes a neuron-to-microglia alarm signal implicated in ALS, and that P2X7 affects autophagy in immune cells, we have investigated if autophagy can be directly triggered by P2X7 activation in primary microglia from superoxide dismutase 1 (SOD1-G93A mice. We report that P2X7 enhances the expression of the autophagic marker microtubule-associated protein 1 light chain 3 (LC3-II, via mTOR pathway and concomitantly with modulation of anti-inflammatory M2 microglia markers. We also demonstrate that the autophagic target SQSTM1/p62 is decreased in SOD1-G93A microglia after a short stimulation of P2X7, but increased after a sustained challenge. These effects are prevented by the P2X7 antagonist A-804598, and the autophagy/phosphoinositide-3-kinase inhibitor wortmannin (WM. Finally, a chronic in vivo treatment with A-804598 in SOD1-G93A mice decreases the expression of SQSTM1/p62 in lumbar spinal cord at end stage of disease. These data identify the modulation of the autophagic flux as a novel mechanism by which P2X7 activates ALS-microglia, to be considered for further investigations in ALS.

  1. 11th International Conference on P2P, Parallel, Grid, Cloud and Internet Computing

    CERN Document Server

    Barolli, Leonard; Amato, Flora

    2017-01-01

    P2P, Grid, Cloud and Internet computing technologies have been very fast established as breakthrough paradigms for solving complex problems by enabling aggregation and sharing of an increasing variety of distributed computational resources at large scale. The aim of this volume is to provide latest research findings, innovative research results, methods and development techniques from both theoretical and practical perspectives related to P2P, Grid, Cloud and Internet computing as well as to reveal synergies among such large scale computing paradigms. This proceedings volume presents the results of the 11th International Conference on P2P, Parallel, Grid, Cloud And Internet Computing (3PGCIC-2016), held November 5-7, 2016, at Soonchunhyang University, Asan, Korea.

  2. Synaptosomal protein synthesis in P2 and Ficoll purified fractions.

    Science.gov (United States)

    Eyman, Maria; Cefaliello, Carolina; Bruno, Anna Paola; Bruno, Annapaola; Crispino, Marianna; Giuditta, Antonio

    2012-01-30

    Cytoplasmic protein synthesis of brain synaptosomes has generally been determined in the Ficoll purified fraction which contains fewer contaminating mitochondria, microsomes and myelin fragments than the parent P2 fraction. Using a highly selective assay of this activity we have compared the total translation activity and the specific activity of the proteins synthesized by either fraction in control rats and in rats trained for a two-way active avoidance task. In control rats the specific activity remained essentially the same in both fractions but in trained rats the value of the Ficoll fraction was markedly lower (38.5%) than in the P2 fraction. Furthermore, the total translation activity of the Ficoll fraction was 30% lower than in the P2 fraction in control rats and 62% lower in trained rats. These decrements indicate that a large proportion of active synaptosomes present in the P2 fraction is not recovered in the Ficoll fraction, notably in rats undergoing plastic brain changes. We conclude that cytoplasmic protein synthesis of brain synaptosomes is better preserved in the P2 fraction. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Determinants of Default in P2P Lending

    Science.gov (United States)

    2015-01-01

    This paper studies P2P lending and the factors explaining loan default. This is an important issue because in P2P lending individual investors bear the credit risk, instead of financial institutions, which are experts in dealing with this risk. P2P lenders suffer a severe problem of information asymmetry, because they are at a disadvantage facing the borrower. For this reason, P2P lending sites provide potential lenders with information about borrowers and their loan purpose. They also assign a grade to each loan. The empirical study is based on loans’ data collected from Lending Club (N = 24,449) from 2008 to 2014 that are first analyzed by using univariate means tests and survival analysis. Factors explaining default are loan purpose, annual income, current housing situation, credit history and indebtedness. Secondly, a logistic regression model is developed to predict defaults. The grade assigned by the P2P lending site is the most predictive factor of default, but the accuracy of the model is improved by adding other information, especially the borrower’s debt level. PMID:26425854

  4. Determinants of Default in P2P Lending.

    Directory of Open Access Journals (Sweden)

    Carlos Serrano-Cinca

    Full Text Available This paper studies P2P lending and the factors explaining loan default. This is an important issue because in P2P lending individual investors bear the credit risk, instead of financial institutions, which are experts in dealing with this risk. P2P lenders suffer a severe problem of information asymmetry, because they are at a disadvantage facing the borrower. For this reason, P2P lending sites provide potential lenders with information about borrowers and their loan purpose. They also assign a grade to each loan. The empirical study is based on loans' data collected from Lending Club (N = 24,449 from 2008 to 2014 that are first analyzed by using univariate means tests and survival analysis. Factors explaining default are loan purpose, annual income, current housing situation, credit history and indebtedness. Secondly, a logistic regression model is developed to predict defaults. The grade assigned by the P2P lending site is the most predictive factor of default, but the accuracy of the model is improved by adding other information, especially the borrower's debt level.

  5. Determinants of Default in P2P Lending.

    Science.gov (United States)

    Serrano-Cinca, Carlos; Gutiérrez-Nieto, Begoña; López-Palacios, Luz

    2015-01-01

    This paper studies P2P lending and the factors explaining loan default. This is an important issue because in P2P lending individual investors bear the credit risk, instead of financial institutions, which are experts in dealing with this risk. P2P lenders suffer a severe problem of information asymmetry, because they are at a disadvantage facing the borrower. For this reason, P2P lending sites provide potential lenders with information about borrowers and their loan purpose. They also assign a grade to each loan. The empirical study is based on loans' data collected from Lending Club (N = 24,449) from 2008 to 2014 that are first analyzed by using univariate means tests and survival analysis. Factors explaining default are loan purpose, annual income, current housing situation, credit history and indebtedness. Secondly, a logistic regression model is developed to predict defaults. The grade assigned by the P2P lending site is the most predictive factor of default, but the accuracy of the model is improved by adding other information, especially the borrower's debt level.

  6. A Technology-Mediated Behavioral Weight Gain Prevention Intervention for College Students: Controlled, Quasi-Experimental Study.

    Science.gov (United States)

    West, Delia Smith; Monroe, Courtney M; Turner-McGrievy, Gabrielle; Sundstrom, Beth; Larsen, Chelsea; Magradey, Karen; Wilcox, Sara; Brandt, Heather M

    2016-06-13

    Both men and women are vulnerable to weight gain during the college years, and this phenomenon is linked to an increased risk of several chronic diseases and mortality. Technology represents an attractive medium for the delivery of weight control interventions focused on college students, given its reach and appeal among this population. However, few technology-mediated weight gain prevention interventions have been evaluated for college students. This study examined a new technology-based, social media-facilitated weight gain prevention intervention for college students. Undergraduates (n =58) in two sections of a public university course were allocated to either a behavioral weight gain prevention intervention (Healthy Weight, HW; N=29) or a human papillomavirus (HPV) vaccination awareness intervention (control; N=29). All students were enrolled, regardless of initial body weight or expressed interest in weight management. The interventions delivered 8 lessons via electronic newsletters and Facebook postings over 9 weeks, which were designed to foster social support and introduce relevant educational content. The HW intervention targeted behavioral strategies to prevent weight gain and provided participants with a Wi-Fi-enabled scale and an electronic physical activity tracker to facilitate weight regulation. A repeated-measures analysis of variance was conducted to examine within- and between-group differences in measures of self-reported weight control practices and objectively measured weight. Use of each intervention medium and device was objectively tracked, and intervention satisfaction measures were obtained. Students remained weight stable (HW: -0.48+1.9 kg; control: -0.45+1.4 kg), with no significant difference between groups over 9 weeks (P =.94). However, HW students reported a significantly greater increase in the number of appropriate weight control strategies than did controls (2.1+4.5 vs -1.1+3.4, respectively; P =.003) and there was no increase in

  7. A Novel Technology for Simultaneous TOC Reduction and Biofouling Prevention, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Recycling of water using biological processes is a primary goal of NASA's advanced life support programs. This proposal concerns a technology to simultaneously...

  8. Bringing the laboratory and clinic to the community: mobile technologies for health promotion and disease prevention.

    Science.gov (United States)

    Kaplan, Robert M; Stone, Arthur A

    2013-01-01

    Health-related information collected in psychological laboratories may not be representative of people's everyday health. For at least 70 years, there has been a call for methods that sample experiences from everyday environments and circumstances. New technologies, including cell phones, sensors, and monitors, now make it possible to collect information outside of the laboratory in environments representative of everyday life. We review the role of mobile technologies in the assessment of health-related behaviors, physiological responses, and self-reports. Ecological momentary assessment offers a wide range of new opportunities for ambulatory assessment and evaluation. The value of mobile technologies for interventions to improve health is less well established. Among 21 randomized clinical trials evaluating interventions that used mobile technologies, more than half failed to document significant improvements on health outcomes or health risk factors. Theoretical and practical issues for future research are discussed.

  9. Applications of Solar Technology for Catastrophe Response, Claims Management, and Loss Prevention

    Energy Technology Data Exchange (ETDEWEB)

    Deering, A.; Thornton, J.P.

    1999-02-17

    Today's insurance industry strongly emphasizes developing cost-effective hazard mitigation programs, increasing and retaining commercial and residential customers through better service, educating customers on their exposure and vulnerabilities to natural disasters, collaborating with government agencies and emergency management organizations, and exploring the use of new technologies to reduce the financial impact of disasters. In June of 1998, the National Renewable Energy Laboratory (NREL) and the National Association of Independent Insurers (NAII) sponsored a seminar titled, ''Solar Technology and the Insurance Industry.'' Presentations were made by insurance company representatives, insurance trade groups, government and state emergency management organizations, and technology specialists. The meeting was attended by insurers, brokers, emergency managers, and consultants from more than 25 US companies. Leading insurers from the personal line and commercial carriers were shown how solar technology can be used in underwriting, claims, catastrophe response, loss control, and risk management. Attendees requested a follow-up report on solar technology, cost, and applications in disasters, including suggestions on how to collaborate with the utility industry and how to develop educational programs for business and consumers. This report will address these issues, with an emphasis on pre-disaster planning and mitigation alternatives. It will also discuss how energy efficiency and renewable technologies can contribute to reducing insurance losses.

  10. The strategic relevance of manufacturing technology: An overall quality concept to promote innovation preventing drug shortage.

    Science.gov (United States)

    Panzitta, Michele; Ponti, Mauro; Bruno, Giorgio; Cois, Giancarlo; D'Arpino, Alessandro; Minghetti, Paola; Mendicino, Francesca Romana; Perioli, Luana; Ricci, Maurizio

    2017-01-10

    Manufacturing is the bridge between research and patient: without product, there is no clinical outcome. Shortage has a variety of causes, in this paper we analyse only causes related to manufacturing technology and we use shortage as a paradigm highliting the relevance of Pharmaceutical Technology. Product and process complexity and capacity issues are the main challenge for the Pharmaceutical Industry Supply chain. Manufacturing Technology should be acknowledged as a R&D step and as a very important matter during University degree in Pharmacy and related disciplines, promoting collaboration between Academia and Industry, measured during HTA step and rewarded in terms of price and reimbursement. The above elements are not yet properly recognised, and manufacturing technology is taken in to consideration only when a shortage is in place. In a previous work, Panzitta et al. proposed to perform a full technology assessment at the Health Technological Assessment stage, evaluating three main technical aspects of a medicine: manufacturing process, physicochemical properties, and formulation characteristics. In this paper, we develop the concept of manufacturing appraisal, providing a technical overview of upcoming challenges, a risk based approach and an economic picture of shortage costs. We develop also an overall quality concept, not limited to GMP factors but broaden to all elements leading to a robust supply and promoting technical innovation. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Collaborative Paradigm of Preventive, Personalized, and Precision Medicine With Point-of-Care Technologies.

    Science.gov (United States)

    Dhawan, Atam P

    2016-01-01

    Recent advances in biosensors, medical instrumentation, and information processing and communication technologies (ICT) have enabled significant improvements in healthcare. However, these technologies have been mainly applied in clinical environments, such as hospitals and healthcare facilities, under managed care by well-trained and specialized individuals. The global challenge of providing quality healthcare at affordable cost leads to the proposed paradigm of P reventive, Personalized, and Precision Medicine that requires a seamless use of technology and infrastructure support for patients and healthcare providers at point-of-care (POC) locations including homes, semi or pre-clinical facilities, and hospitals. The complexity of the global healthcare challenge necessitates strong collaborative interdisciplinary synergies involving all stakeholder groups including academia, federal research institutions, industry, regulatory agencies, and clinical communities. It is critical to evolve with collaborative efforts on the translation of research to technology development toward clinical validation and potential healthcare applications. This special issue is focused on technology innovation and translational research for POC applications with potential impact in improving global healthcare in the respective areas. Some of these papers were presented at the NIH-IEEE Strategic Conference on Healthcare Innovations and POC Technologies for Precision Medicine (HI-POCT) held at the NIH on November 9-10, 2015. The papers included in the Special Issue provide a spectrum of critical issues and collaborative resources on translational research of advanced POC devices and ICT into global healthcare environment.

  12. Power-to-Gas (P2G), a flexibility tool to accompany the transformation of the energy system

    International Nuclear Information System (INIS)

    Courtecuisse, Matthieu; Lorgeril, Charlotte de; Courtemanche, Noel

    2015-01-01

    Power-to-Gas (P2G) is one of the envisaged solutions to the problem of production intermittency of renewable energies, of energy storage and peak consumption management. This Power Point presentation proposes a rather detailed overview of the possibilities and perspectives of this technology. It addresses the context and stakes of P2G: challenges related to the transformation of the energy system, implemented technologies. Different technologies are presented with their drawbacks and benefits, their main actors, their maturity level: electrolysis (alkaline, proton exchange membrane, solid oxide electrolysis), methanation (chemical, biological, CO 2 capture). It proposes a presentation of the various actors in European countries: energy industries, P2G component providers and experts, research organisations, public bodies and associations, political field. P2G European projects are then presented: studies, R and D projects, demonstrators. The last part proposes an overview of the regulatory, environmental, safety and acceptability issues

  13. Synthesis of Amylose-b-P2 VP Block Copolymers.

    Science.gov (United States)

    Kumar, Kamlesh; Woortman, Albert J J; Loos, Katja

    2015-12-01

    A new class of rod-coil block copolymers is synthesized by chemoenzymatic polymerization. In the first step, maltoheptaose, which acts as a primer for the synthesis of amylose, is attached to poly(2-vinyl pyridine) (P2 VP). The enzymatic polymerization of maltoheptaose is carried out by phosphorylase to obtain amylose-b-P2 VP block copolymers. The block copolymer is characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, gel permeation chromatography, and wide-angle X-ray scattering techniques. The designed molecules combine the inclusion complexation ability of amylose with the supramolecular complexation ability of P2 VP and therefore this kind of rod-coil block copolymers can be used to generate well-organized novel self-assembled structures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Ion Exchange Technology Development in Support of the Urine Processor Assembly Precipitation Prevention Project for the International Space Station

    Science.gov (United States)

    Mitchell, Julie L.; Broyan, James L.; Pickering, Karen D.; Adam, Niklas; Casteel, Michael; Callahan, Michael; Carrier, Chris

    2012-01-01

    In support of the Urine Processor Assembly Precipitation Prevention Project (UPA PPP), multiple technologies were explored to prevent CaSO4 2H2O (gypsum) precipitation during the on-orbit distillation process. Gypsum precipitation currently limits the water recovery rate onboard the International Space Station (ISS) to 70% versus the planned 85% target water recovery rate. Due to its ability to remove calcium cations in pretreated augmented urine (PTAU), ion exchange was selected as one of the technologies for further development by the PPP team. A total of 13 ion exchange resins were evaluated in various equilibrium and dynamic column tests with solutions of dissolved gypsum, urine ersatz, PTAU, and PTAU brine at 85% water recovery. While initial evaluations indicated that the Purolite SST60 resin had the highest calcium capacity in PTAU (0.30 meq/mL average), later tests showed that the Dowex G26 and Amberlite FPC12H resins had the highest capacity (0.5 meq/mL average). Testing at the Marshall Spaceflight Center (MSFC) integrates the ion exchange technology with a UPA ground article under flight-like pulsed flow conditions with PTAU. To date, no gypsum precipitation has taken place in any of the initial evaluations.

  15. Nutritional "omics" technologies for elucidating the role(s) of bioactive food components in colon cancer prevention.

    Science.gov (United States)

    Davis, Cindy D; Hord, Norman G

    2005-11-01

    Evidence continues to implicate dietary components and genetic susceptibilities as important determinants of cancer risk and tumor behavior. Variation in cancer incidence among and within populations with similar dietary patterns suggests that an individual's response may reflect interactions with genetic factors, which may modify gene, protein, and metabolite expression patterns. Nutrigenomics, defined as the interaction between nutrition and an individual's genome, will likely provide important clues about responders and nonresponders. In this symposium, the role of bioactive food components in colon cancer susceptibility was used to exemplify the application of "omic" technologies for cancer prevention. Topics that were addressed included dietary changes and gene polymorphisms (nutrigenetics), DNA methylation (nutritional epigenomics), gene expression (nutritional transcriptomics), altered formation or bioactivation of proteins (proteomics), and characterizing how the quantity and timing of exposure influence small molecular weight cellular constituents (metabolomics). The final presentation focused on exfoliated cells as a surrogate sample for the evaluation of bioactive food components in cancer prevention. The goal of the symposium was to provide an example of each of the "omic" technologies as they relate to nutrition, cancer risk, and tumor behavior, and to help the participants understand that an integrated framework that simultaneously examines all of the "omic" technologies is needed.

  16. Young Women's Ratings of Three Placebo Multipurpose Prevention Technologies for HIV and Pregnancy Prevention in a Randomized, Cross-Over Study in Kenya and South Africa.

    Science.gov (United States)

    Minnis, Alexandra M; Roberts, Sarah T; Agot, Kawango; Weinrib, Rachel; Ahmed, Khatija; Manenzhe, Kgahlisho; Owino, Fredrick; van der Straten, Ariane

    2018-03-20

    End-user input is critical to inform development of multipurpose prevention technology (MPT) products that prevent HIV and pregnancy. The TRIO Study, conducted in Kenya and South Africa, enrolled 277 HIV-negative women aged 18-30 in a randomized cross-over study to use each placebo MPT (daily oral tablets, monthly injections, and monthly vaginal ring) for one month. At the end of each month, participants rated how much they liked using the product on a 5-point Likert scale (5 = liked very much). We compared mean ratings using paired t-tests and examined sociodemographic-, attribute-, and behavior-related characteristics associated with ratings using multivariable linear regression and data from in-depth interviews. After use, mean ratings were significantly higher for injections [4.3 (SD = 1.0)] compared with tablets [3.0 (SD = 1.3)] and rings [3.3 (SD = 1.4)] (p < 0.001); mean ratings for rings were significantly higher than for tablets (p = 0.013). Mean ratings of a hypothetical active MPT increased for all products after the one-month period of use, with the greatest increase for rings, the least familiar product. In multivariable analysis, acceptability of key product attributes (e.g., product look) were associated with a significant increase of ≥ 1 point in the mean rating across all three products (p ≤ 0.001). Perceived ability to use the product without partner knowledge was associated with a higher mean rating for rings (b = 0.50; p = 0.006). The acceptability of product attributes contributed significantly to the rating of all products, highlighting the value of choice in pregnancy and HIV prevention to accommodate diverse users.

  17. Improving Management Performance of P2PSIP for Mobile Sensing in Wireless Overlays

    Science.gov (United States)

    Sendín-Raña, Pablo; González-Castaño, Francisco Javier; Gómez-Cuba, Felipe; Asorey-Cacheda, Rafael; Pousada-Carballo, José María

    2013-01-01

    Future wireless communications are heading towards an all-Internet Protocol (all-IP) design, and will rely on the Session Initiation Protocol (SIP) to manage services, such as voice over IP (VoIP). The centralized architecture of traditional SIP has numerous disadvantages for mobile ad hoc services that may be possibly overcome by advanced peer-to-peer (P2P) technologies initially developed for the Internet. In the context of mobile sensing, P2PSIP protocols facilitate decentralized and fast communications with sensor-enabled terminals. Nevertheless, in order to make P2PSIP protocols feasible in mobile sensing networks, it is necessary to minimize overhead transmissions for signaling purposes, which reduces the battery lifetime. In this paper, we present a solution to improve the management of wireless overlay networks by defining an adaptive algorithm for the calculation of refresh time. The main advantage of the proposed algorithm is that it takes into account new parameters, such as the delay between nodes, and provides satisfactory performance and reliability levels at a much lower management overhead than previous approaches. The proposed solution can be applied to many structured P2P overlays or P2PSIP protocols. We evaluate it with Kademlia-based distributed hash tables (DHT) and dSIP PMID:24217358

  18. Transforming environmental permitting and compliance policies to promote pollution prevention: Removing barriers and providing incentives to foster technology innovation, economic productivity, and environmental protection. Final report

    International Nuclear Information System (INIS)

    Berg, D.R.; Kerr, R.L.; Fleischer, S.; Gorsen, M.; Harris, E.

    1993-04-01

    The Technology Innovation and Economics (TIE) Committee, a standing committee of EPA's National Advisory Council for Environmental Policy and Technology (NACEPT), has concluded that major changes are needed in federal and state permitting and compliance programs to encourage adoption of practical pollution prevention approaches to environmental protection. The Committee recommends seven major areas for improvement, including: (1) Redesigning permit procedures to encourage regulated facilities to expand multi-media and pollution prevention environmental improvement efforts; (2) Accelerating development and use of innovative pollution prevention technologies and techniques through special permitting and review procedures during RD ampersand D and commercialization phases; (3) Developing and expanding federal and state pollution prevention enforcement initiative; (4) Supporting state initiatives in pollution prevention facility planning; (5) Expanding pollution prevention-related training, educational and technology diffusion efforts to better reach managers in all sectors of the economy; (6) Altering personnel reward systems to encourage EPA staff to champion pollution prevention; (7) Expanding and publicizing the system of national awards honoring outstanding pollution prevention research, training and technology implementation

  19. Mobile P2P Web Services Using SIP

    Directory of Open Access Journals (Sweden)

    Guido Gehlen

    2007-01-01

    Full Text Available Telecommunication networks and the Internet are growing together. Peer-to-Peer (P2P services which are originally offered by network providers, like telephony and messaging, are provided through VoIP and Instant Messaging (IM by Internet service providers, too. The IP Multimedia Subsystem (IMS is the answer of the telecommunication industry to this trend and aims at providing Internet P2P and multimedia services controlled by the network operators. The IMS provides mobility and session management as well as message routing, security, and billing.

  20. Secure P2P Data Storage and Maintenance

    Directory of Open Access Journals (Sweden)

    Nouha Oualha

    2010-01-01

    Full Text Available P2P data storage requires strong reliability and security assurances. Existing data storage solutions have been designed for centralized as well as distributed settings; yet they do not address the security and cooperation issues raised by self-organization. P2P systems also introduce new needs regarding data availability due to the dynamicity of the infrastructure, which are unaddressed so far. This paper first discusses the approaches for tackling these problems. A solution is then introduced that relies on self-organizing security mechanisms in conjunction with a data rejuvenation scheme using erasure codes.

  1. Providing Consultation to Primary Prevention Programs: Applying the Technology of Community Psychology.

    Science.gov (United States)

    Weed, David S.

    Nationwide attention to the problems of teenage pregnancy and suicide, Acquired Immune Deficiency Syndrome (AIDS), substance abuse, domestic violence, child abuse, dropping out of school, and other conditions is resulting in a proliferation of primary prevention programs, projects, and activities. In too many communities, however, the growth of…

  2. Lessons learned from the development of technological support for PTSD prevention : A review

    NARCIS (Netherlands)

    Vakili, V.; Brinkman, W.P.; Neerincx, M.A.

    2012-01-01

    This review2 describes the state-of-the-arttechnologiesthat support mental resilience training for PTSD prevention. It characterizes four current systems across training approaches; seeks insights via interviews with the systemdevelopers; and extracts from thesea set of essential guidelines for

  3. [Innovations on technology, management and concept are indispensible for scientific research, prevention and treatment of malignant tumor in China].

    Science.gov (United States)

    Cao, G W

    2017-01-10

    Malignant tumor has become the top cause of deaths before the average life expectancy in Chinese population. From the variations in the morbidity rate and mortality rate of malignant tumor in the mainland of China between 2000 and 2011, the primary prevention targeting the risk factors/etiological agents significantly reduced the morbidity rates of gastric cancer, esophageal cancer, and primary liver cancer, therefore reduced the mortality rates of these cancers. However, the contribution of clinical treatments to the mortality reduction was not obviously improved during this period. Importantly, it is necessary to conduct research to identify precancerous lesions and early tumors which are prone to progress to aggressive diseases for the active secondary prevention to avoid over-diagnosis and over-treatment. Multi-center, prospective randomized controlled clinical trials and prognosis evaluation independently carried out by third parts are needed to evaluate the longterm effectiveness of some clinical treatment efficiency for cancers with different histological types. On the basis of a series of population-based studies in China, the prevention and clinical treatments for malignant tumor need innovations on technology, management, and even concept; the mechanisms of "forward placement of strategic pass" for the prevention and control of malignant tumor should be established and improved to reduce the increasing disease burden due to malignant tumor in China.

  4. intensifying and reorienting transfer of low carbon technologies for climate change prevention

    International Nuclear Information System (INIS)

    Pisani-Ferry, Jean; Monange, Herve; Gorges, Delphine; Senne, Valerie; Roulle, Jean-Michel

    2013-10-01

    The transfer of 'low carbon' technologies is crucial in order to moderate greenhouse gas (GHG) emissions by developing countries, which are set to rise significantly. Their implementation will determine the success of a global agreement on climate change in 2015, and this is the task of the Technology Mechanism, created in 2010. This policy brief sets out the principal results of a study commissioned from the Mines ParisTech Industrial Economics Centre (CERNA). The study shows that, unlike China, Mexico, South Africa and, to a lesser extent, Brazil, India is currently left out of international flows of low carbon technologies transfer - it is therefore a top priority, as is the rest of developing Asia, Africa and Eastern Europe. To intensify these transfers, ambitious greenhouse gas emissions reduction policies need to be implemented and absorptive capacities need to be created in countries that receive such technologies. In emerging countries, which possess a genuine capacity for innovation, and which are involved in international trade, the strengthening of intellectual property rights and the lowering of barriers to trade and investment are to be recommended. However, in the least developed countries, emphasis must be placed on technology absorptive capacities and in particular on the development of a qualified labour force

  5. Comparing Pedophile Activity in Different P2P Systems

    Directory of Open Access Journals (Sweden)

    Raphaël Fournier

    2014-07-01

    Full Text Available Peer-to-peer (P2P systems are widely used to exchange content over the Internet. Knowledge of pedophile activity in such networks remains limited, despite having important social consequences. Moreover, though there are different P2P systems in use, previous academic works on this topic focused on one system at a time and their results are not directly comparable. We design a methodology for comparing KAD and eDonkey, two P2P systems among the most prominent ones and with different anonymity levels. We monitor two eDonkey servers and the KAD network during several days and record hundreds of thousands of keyword-based queries. We detect pedophile-related queries with a previously validated tool and we propose, for the first time, a large-scale comparison of pedophile activity in two different P2P systems. We conclude that there are significantly fewer pedophile queries in KAD than in eDonkey (approximately 0.09% vs. 0.25%.

  6. P2X(3) receptor gating near normal body temperature

    Czech Academy of Sciences Publication Activity Database

    Kmyhz, V.; Maximyuk, O.; Teslenko, V.; Verkhratsky, Alexei; Krishtal, O.

    2008-01-01

    Roč. 456, č. 12 (2008), s. 339-347 ISSN 0031-6768 Institutional research plan: CEZ:AV0Z50390703 Keywords : P2X3 receptors * Temperature-sensitivity * Gating Subject RIV: FH - Neurology Impact factor: 3.526, year: 2008

  7. P2X receptor channels in endocrine glands

    Czech Academy of Sciences Publication Activity Database

    Stojilkovic, S. S.; Zemková, Hana

    2013-01-01

    Roč. 2, č. 4 (2013), s. 173-180 ISSN 2190-460X R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : ATP * purinergic P2X receptor channels * pituitary * endocrine glands Subject RIV: ED - Physiology

  8. The P2 Masonic Lodge and Ceaușescu

    Directory of Open Access Journals (Sweden)

    Sabin Drăgulin

    2013-02-01

    Full Text Available In the following article the author aims at proving that Nicolae Ceausescu wasn't e member of the P2 masonic lodge. The conclusion has been driven following an in depth research conducted in the archives of the Italian state.

  9. Review of Brookhaven nuclear transparency measurements in (p,2p ...

    Indian Academy of Sciences (India)

    Review of Brookhaven nuclear transparency measurements in (p,2p) reactions at large Q. 2. ALAN S CARROLL. Collider-Accelerator Department, Brookhaven National Laboratory, Upton, NY 11973, USA. Abstract. In this contribution we summarize the results of two experiments to measure the trans- parency of nuclei in ...

  10. Functionalized Congeners of P2Y1 Receptor Antagonists:

    Energy Technology Data Exchange (ETDEWEB)

    de Castro, Sonia [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Maruoka, Hiroshi [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Hong, Kunlun [ORNL; Kilbey, II, S Michael [ORNL; Costanzi, Stefano [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Hechler, Béatrice [University of Strasbourg; Gachet, Christian [EFS-Alsace, Strasbourg, France; Harden, T. Kendall [University of North Carolina School of Medicine; Jacobson, Kenneth A. [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health

    2010-01-01

    The P2Y{sub 1} receptor is a prothrombotic G protein-coupled receptor (GPCR) activated by ADP. Preference for the North (N) ring conformation of the ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of the P2Y{sub 1} receptor was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute. A series of covalently linkable N{sup 6}-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphates containing extended 2-alkynyl chains was designed, and binding affinity at the human (h) P2Y{sub 1} receptor determined. The chain of these functionalized congeners contained hydrophilic moieties, a reactive substituent, or biotin, linked via an amide. Variation of the chain length and position of an intermediate amide group revealed high affinity of carboxylic congener 8 (K{sub i} 23 nM) and extended amine congener 15 (K{sub i} 132 nM), both having a 2-(1-pentynoyl) group. A biotin conjugate 18 containing an extended {epsilon}-aminocaproyl spacer chain exhibited higher affinity than a shorter biotinylated analogue. Alternatively, click coupling of terminal alkynes of homologous 2-dialkynyl nucleotide derivatives to alkyl azido groups produced triazole derivatives that bound to the P2Y{sub 1} receptor following deprotection of the bisphosphate groups. The preservation of receptor affinity of the functionalized congeners was consistent with new P2Y{sub 1} receptor modeling and ligand docking. Attempted P2Y{sub 1} antagonist conjugation to PAMAM dendrimer carriers by amide formation or palladium-catalyzed reaction between an alkyne on the dendrimer and a 2-iodopurine-derivatized nucleotide was unsuccessful. A dialkynyl intermediate containing the chain length favored in receptor binding was conjugated to an azide-derivatized dendrimer, and the conjugate inhibited ADP-promoted human platelet aggregation. This is the first example of attaching a strategically functionalized P2Y receptor

  11. Evidence for requirement of tyrosine phosphorylation in endothelial P2Y- and P2U- purinoceptor stimulation of prostacyclin release.

    Science.gov (United States)

    Bowden, A.; Patel, V.; Brown, C.; Boarder, M. R.

    1995-01-01

    1. The release of prostacyclin (PGI2) from vascular endothelial cells is stimulated by ATP acting at G protein-coupled P2-purinoceptors. Here we investigate the hypothesis that tyrosine protein phosphorylations are involved in this response. 2. The use of Western blots with anti-phosphotyrosine antibodies showed that 30 microM 2MeSATP (selective for P2Y-purinoceptors), 300 microM UTP (selective for P2U-purinoceptors) and 300 microM ATP (effective at both these purinoceptors), each stimulate the tyrosine phosphorylation of proteins in bovine cultured aortic endothelial cells. Each of these agonists also stimulates 6-keto PGF1 alpha accumulation in the medium (an index of PGI2 release) in these cells in the same period. 3. The tyrosine kinase inhibitor, genistein, inhibits the 6-keto PGF1 alpha response with the same concentration-dependency (1-100 microM) as the tyrosine phosphorylation response. 4. Tyrphostin, a structurally and functionally distinct tyrosine kinase inhibitor, is also a potent inhibitor (0.1-10 microM) of the 6-keto PGF1 alpha response. 5. Neither tyrphostin nor genistein inhibit the phospholipase C response to P2-purinoceptor stimulation. Furthermore, these inhibitors do not affect the 6-keto PGF1 alpha response to ionomycin. 6. These results show that the regulation of vascular endothelial cells by ATP acting at both P2Y- and P2U-purinoceptors involves the stimulation of tyrosine phosphorylation, and suggest that this is a necessary event for the purinoceptor-mediated stimulation of PGI2 production. Images Figure 1 Figure 5 PMID:8590971

  12. VITAMIN PREVENTIVE ALGORITHM FOR CHILDREN WITH ACUTE RESPIRATORY DISEASES: TECHNOLOGY OF INCREASING NON SPECIFIC RESISTANCE

    Directory of Open Access Journals (Sweden)

    O.A. Gromova

    2007-01-01

    Full Text Available An algorithm of choosing adequate vitamin combination for children's acute respiratory diseases is suggested on the basis of Pikovit vitamin complex (KRKA, Slovenia. It is emphasized that the choice of vitamins should be based on the peculiarities of their metabolism and their role in the body. The importance of vitamin therapy is in its immunomodifying effect and increasing child's abilities for adaptation. Choice of vitamin and mineral complex for seasonal child ARD prevention depends on physiological vitamin doses and the fact that vitamin and mineral complexes containing iron and copper should be excluded in the acute phase of the disease. Latest research data is provided demonstrating the inadvisability of using iron and copper additives to children with ARD. The article provides information on the necessity of qualified primary inspection of the sick child, diagnosing activities, composing an individual diet, vitamin and pharmacological therapy.Key words: polyvitamin products, prevention, acute respiratory infections, children.

  13. Using smart card technology to prevent sales of alcohol to underage persons

    Science.gov (United States)

    2001-07-01

    This report documents the results of a demonstration and evaluation project to examine the effectiveness of smart card technology (i.e., magnetic stripe on the driver's license and a card reader system) as a means of providing alcohol retailers with ...

  14. Preventing technology-induced errors in healthcare: the role of simulation.

    Science.gov (United States)

    Kushniruk, Andre W; Borycki, Elizabeth M; Anderson, James G; Anderson, Marilyn M

    2009-01-01

    We describe a novel approach to the study and prediction of technology-induced error in healthcare. The objective of our approach is to identify and reduce the potential for error so that the benefits of introducing information technology, such as Computerized Physician Order Entry (CPOE) or Electronic Health Records (EHRs), are maximized. The approach involves four phases. In Phase 1, we typically conduct small scale clinical simulations to assess whether or not the use of a new information technology can introduce error. (Human subjects are involved and user-system interactions are recorded.) In Phase 2, we analyze the results from Phase 1 to identify statistically significant relationships between usability issues and the occurrence of error (e.g., medication error). In Phase 3, we enter the results from Phase 2 into computer-based simulation models to explore the potential impact of the technology over time and across user populations. In Phase 4, we conduct naturalistic studies to examine whether or not the predictions made in Phases 2 and 3 apply to the real world. In closing, we discuss how the approach can be used to increase the safety of health information systems.

  15. EFEKTIVITAS METODE P2R UNTUK MENINGKATKAN KECEPATAN EFEKTIF MEMBACA (KEM MAHASISWA CALON GURU BAHASA INDONESIA

    Directory of Open Access Journals (Sweden)

    Nurmina

    2015-12-01

    Full Text Available Reading is one of language skill which is not less important compared with others language skill such as scrutinizing, speaking, and writing. In this era which technology is flaring and developing rapidly, the students are prefer to play facebook, twitter, chatting, and many more than read a journal or articles. This phenomenon shows that the interest to read among students is needed to be increased. One of the way that can be taken is by having skills to read quickly or is known by scanning with P2R method. The P2R method itself is one of method or strategy that can be used to increase reading skill. The P2R method consists of stages pra-peninjauan, membaca, dan meninjau that commonly used by the most of quick reader / scanner and efficient. This research is done to obtain data about the effective reading speed of student as Indonesian language teacher candidate and the effort of its increasing through the P2R method. The population of this research is all students on program of study Indonesian language and literature education and also area of Almuslim University as much 149 students. The sample of this research is 30% of the total population or as much 45 strudents of Indonesia Language teacher candidate of Almuslim University who are taken randomly. The type of research is experimental research (true experimental and quantitative approach with the model of research is pretest-post test control group model. The result of research shows that the P2R method is effective to be implemented to increase the effective reading speed of students as Indonesian language teacher candidate. FKIP is obtained by researcher. The posttest result shows that there was an increasing of KEM learning outcomes meanwhile the observation result was seems that in the learning with P2R model, the students were very enthusiasm, more active, also more motivated in attending the learning. Besides that, the result of questionnaires also shows that the P2R method obtained

  16. Disaster-Proofing Senior Leadership: Preventing Technological Failure in Future Nano-War

    Science.gov (United States)

    2009-02-01

    weight of a paper clip using technology from a blow fly. 4. Davis, “Nano Air Vehicles,” 4. 5. CSAT Reference to Failed State Scenario. 6. Hooper...Basically there are three options – threats, customers , or opportunities.12 The negative view would see these rising powers as threatening competitors with...with a huge and growing potential customer base. The third view would see the growing power and influence of these three nations in their regions as

  17. Theatrical distribution and P2P movie piracy: a survey of P2P networks in Hungary using transactional data

    NARCIS (Netherlands)

    Bodó, B.; Lakatos, Z.

    2012-01-01

    This article examines what appears to be the most important factor shaping file sharing: the failure of traditional cultural markets to efficiently supply the demand in the online environment. Its findings are based on tracking the traffic of movies on three Hungarian P2P networks. This dataset is

  18. Evaluation of satellite technology for pipeline route surveillance and the prevention of third party interference damage

    Energy Technology Data Exchange (ETDEWEB)

    Palmer-Jones, Roland; Hopkins, Phil [Penspen Integrity, Newcastle upon Tyne (United Kingdom)]. E-mail: r.palmer-jones@penspen.com; p.hopkins@penspen.com; Fraser, Andy [Integrated Statistical Solutions (United States)]. E-mail: andy@issquared.co.uk; Dezobry, Jerome [Gas de France, Paris (France)]. E-mail: jerome.dezobry@gazdefrance.com; Merrienboer, Hugo Van [Gasunie, Groningen (Netherlands)]. E-mail: H.A.M.van.Merrienboer@gasunie.nl

    2003-07-01

    The damage caused by Third Party Interference (TPI) is one of the major causes of pipeline failures. Consequently, new technologies for identifying activities that may cause damage to our pipelines are constantly being developed. A recently completed project sponsored by a number of pipeline operators has investigated the use of high-resolution satellites for the integrity management of onshore transmission pipelines. The sponsors were BG Technology (on behalf of Transco), Dansk Olie NatureGas, Gasunie, BP, Gaz de France, Distrigas, and the Health and Safety Executive. The project started with a general review of the satellite technologies available and their potential. The study was then focussed on the identification of activities that might result in damage to the pipeline and the potential of high-resolution optical satellites in identifying hazardous activities. A key element of the study was a comparison with existing surveillance systems, which generally involve regular aerial patrols of the pipeline route. To achieve this a survey was carried out to try and evaluate the costs and benefits of existing systems. In addition a simple model for analysing the cost benefit of pipeline surveillance was constructed, and a functional specification for a surveillance system drafted. Finally the performance of the IKONOS 2 high-resolution satellite system was tested in a controlled experiment using targets placed along a pipeline route. The results of this test were compared with a similar test of helicopter-based surveillance carried out by one of the sponsors. (author)

  19. Role of P2X purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats.

    Directory of Open Access Journals (Sweden)

    Sheng Chen

    Full Text Available INTRODUCTION: Neurogenic pulmonary edema (NPE is an acute and serious complication after subarachnoid hemorrhage (SAH with high mortality. The present study aimed to test the therapeutic potential of brilliant blue G (BBG, a selective P2X purinoceptor 7 (P2X7R antagonist, on NPE in a rat SAH model. METHODS: SAH was induced by endovascular perforation. 86 Sprague-Dawley rats were randomly divided into sham, vehicle-, or BBG-treatment groups. Mortality, body weight, SAH grading, neurological deficits, NPE clinical symptoms, and pulmonary index were measured at 24 hours following SAH. Western blot, gelatin zymography, lung histopathology, and immunofluorescence staining were performed in the left lung lobe to explore the underlying mechanisms at 24 hours post-surgery. RESULTS: The incidence of clinical symptoms was correlated with pulmonary index. P2X7R and the marker of alveolar type I epithelial cells (the mucin-type glycoprotein T1-α immunoreactivities were generally co-localized. BBG administration decreased mature interleukin-1β, myeloperoxidase, and matrix metallopeptidase-9 activation, but increased tight junction proteins, such as ZO-1 and occludin, which ameliorated pulmonary edema via anti-inflammation and improved neurological deficits. CONCLUSION: P2X7R inhibition prevented NPE after SAH by attenuating inflammation. Thus, BBG is a potential therapeutic application for NPE after SAH and warrants further research.

  20. Development of a technology-based behavioral vaccine to prevent adolescent depression: A health system integration model

    Directory of Open Access Journals (Sweden)

    Benjamin W. Van Voorhees

    2015-09-01

    Full Text Available Efforts to prevent depression have become a key health system priority. Currently, there is a high prevalence of depression among adolescents, and treatment has become costly due to the recurrence patterns of the illness, impairment among patients, and the complex factors needed for a treatment to be effective. Primary care may be the optimal location to identify those at risk by offering an Internet-based preventive intervention to reduce costs and improve outcomes. Few practical interventions have been developed. The models for Internet intervention development that have been put forward focus primarily on the Internet component rather than how the program fits within a broader context. This paper describes the conceptualization for developing technology based preventive models for primary care by integrating the components within a behavioral vaccine framework. CATCH-IT (Competent Adulthood Transition with Cognitive-behavioral, Humanistic and Interpersonal Training has been developed and successfully implemented within various health systems over a period of 14 years among adolescents and young adults aged 13–24.

  1. Supporting seamless mobility for P2P live streaming.

    Science.gov (United States)

    Kim, Eunsam; Kim, Sangjin; Lee, Choonhwa

    2014-01-01

    With advent of various mobile devices with powerful networking and computing capabilities, the users' demand to enjoy live video streaming services such as IPTV with mobile devices has been increasing rapidly. However, it is challenging to get over the degradation of service quality due to data loss caused by the handover. Although many handover schemes were proposed at protocol layers below the application layer, they inherently suffer from data loss while the network is being disconnected during the handover. We therefore propose an efficient application-layer handover scheme to support seamless mobility for P2P live streaming. By simulation experiments, we show that the P2P live streaming system with our proposed handover scheme can improve the playback continuity significantly compared to that without our scheme.

  2. Supporting Seamless Mobility for P2P Live Streaming

    Directory of Open Access Journals (Sweden)

    Eunsam Kim

    2014-01-01

    Full Text Available With advent of various mobile devices with powerful networking and computing capabilities, the users' demand to enjoy live video streaming services such as IPTV with mobile devices has been increasing rapidly. However, it is challenging to get over the degradation of service quality due to data loss caused by the handover. Although many handover schemes were proposed at protocol layers below the application layer, they inherently suffer from data loss while the network is being disconnected during the handover. We therefore propose an efficient application-layer handover scheme to support seamless mobility for P2P live streaming. By simulation experiments, we show that the P2P live streaming system with our proposed handover scheme can improve the playback continuity significantly compared to that without our scheme.

  3. P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions

    Science.gov (United States)

    Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul

    2015-01-01

    ABSTRACT HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. IMPORTANCE Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1

  4. Efficient Content Distribution in P2P and Cloud Service

    OpenAIRE

    E. Priya; A. Samydurai; T. Amitha

    2014-01-01

    Increasing the performance of cloud downloading service in a peer-peer network by efficient mode selection method. Using P2P to download video content often faces challenges like high bandwidth requirement, dealing with a huge number of peer requests, resulting in inefficient system performance. The latest premium service to have been developed is the cloud downloading. In this service, cloud storage is used to store the video content. The server is used to cache the user interested video con...

  5. Pure P2P mediation system: A mappings discovery approach

    Science.gov (United States)

    selma, El yahyaoui El idrissi; Zellou, Ahmed; Idri, Ali

    2015-02-01

    The information integration systems consist in offering a uniform interface to provide access to a set of autonomous and distributed information sources. The most important advantage of this system is that it allows users to specify what they want, rather than thinking about how to get the responses. The works realized in this area have particular leads to two major classes of integration systems: the mediation systems based on the paradigm mediator / adapter and peer to peer systems (P2P). The combination of both systems has led to a third type; is the mediation P2P systems. The P2P systems are large-scale systems, self-organized and distributed. They allow the resource management in a completely decentralized way. However, the integration of structured information sources, heterogeneous and distributed proves to be a complex problem. The objective of this work is to propose an approach to resolve conflicts and establish a mapping between the heterogeneous elements. This approach is based on clustering; the latter is to group similar Peers that share common information in the same subnet. Thus, to facilitate the heterogeneity, we introduced three additional layers of our hierarchy of peers: internal schema, external schema and Schema directory peer. We used linguistic techniques, and precisely the name correspondence technique, that is based on the similarity of names to propose a correspondence.

  6. An Overlapping Structured P2P for REIK Overlay Network

    Science.gov (United States)

    Liu, Wenjun; Song, Jingjing; Yu, Jiguo

    REIK is based on a ring which embedded an inverse Kautz digraph, to enable multi-path P2P routing. It has the constant degree and the logarithmic diameter DHT scheme with constant congestion and Byzantine fault tolerance. However, REIK did not consider the interconnection of many independent smaller networks. In this paper, we propose a new approach to build overlay network, OLS-REIK which is an overlapping structured P2P for REIK overlay network. It is a more flexible interconnecting different REIK network. Peers can belong to several rings, allowing this interconnection. By connecting smaller structured overlay networks in an unstructured way, it provides a cost effective alternative to hierarchical structured P2P systems requiring costly merging. Routing of lookup messages is performed as in REIK within one ring, but a peer belonging to several rings forwards the request to the different rings it belongs to. Furthermore a small number of across point is enough to ensure a high exhaustiveness level.

  7. Pollution prevention opportunity assessment for building 878, manufacturing science and technology, organization 14100.

    Energy Technology Data Exchange (ETDEWEB)

    Klossner, Kristin Ann

    2004-05-01

    This report describes the methodology, analysis and conclusions of a preliminary assessment carried out for activities and operations at Sandia National Laboratories Building 878, Manufacturing Science and Technology, Organization 14100. The goal of this assessment is to evaluate processes being carried out within the building to determine ways to reduce waste generation and resource use. The ultimate purpose of this assessment is to analyze and prioritize processes within Building 878 for more in-depth assessments and to identify projects that can be implemented immediately.

  8. Surgical site infection after total en bloc spondylectomy: risk factors and the preventive new technology.

    Science.gov (United States)

    Hayashi, Hiroyuki; Murakami, Hideki; Demura, Satoru; Kato, Satoshi; Yoshioka, Katsuhito; Shinmura, Kazuya; Yokogawa, Noriaki; Ishii, Takayoshi; Fang, Xiang; Shirai, Toshiharu; Tsuchiya, Hiroyuki

    2015-01-01

    Surgical site infection (SSI) associated with instruments remains a serious and common complication in patients who undergo total en bloc spondylectomy (TES). It is very important that the risk factors for SSI are known to prevent it. The purpose of the study was to identify independent risk factors for SSI after TES and evaluate the positive effect of iodine-supported spinal instruments in the prevention of SSI after TES. This is a retrospective clinical study. One hundred twenty-five patients who underwent TES for vertebral tumor were evaluated. Incidence rate of SSI, risk factors for SSI after TES, and safety of iodine-supported spinal instruments were the outcome measures. Risk factors for SSI were analyzed using logistic regression. In recent 69 patients with iodine-supported spinal instruments, the thyroid hormone levels in the blood were examined to confirm if iodine from the implant influenced thyroid function. Postoperative radiological evaluations were performed regularly. The rate of SSI was 6.4% (8/125 patients). By multivariate logistic regression, combined anterior and posterior approach and nonuse of iodine-supported spinal instruments were associated with an increased risk of SSI. The rate of SSI without iodine-supported spinal instruments was 12.5%, whereas the rate with iodine-supported spinal instruments was 1.4%. This difference was statistically significant. There were no detected abnormalities of thyroid gland function with the use of iodine-supported instruments. Among the 69 patients with iodine-supported spinal instruments, 2 patients required additional surgery because of instrument failure. However, there were no obvious involvements with the use of iodine-supported spinal instruments. This study identified combined anterior and posterior approach and nonuse of iodine-supported spinal instruments to be independent risk factors for SSI after TES. Iodine-supported spinal instrument was extremely effective for prevention of SSI in patients

  9. Scalable P2P Overlays of Very Small Constant Degree: An Emerging Security Threat

    Science.gov (United States)

    Jelasity, Márk; Bilicki, Vilmos

    In recent years peer-to-peer (P2P) technology has been adopted by Internet-based malware as a fault tolerant and scalable communication medium for self-organization and survival. It has been shown that malicious P2P networks would be nearly impossible to uncover if they operated in a stealth mode, that is, using only a small constant number of fixed overlay connections per node for communication. While overlay networks of a small constant maximal degree are generally considered to be unscalable, we argue in this paper that it is possible to design them to be scalable, efficient and robust. This is an important finding from a security point of view: we show that stealth mode P2P malware that is very difficult to discover with state-of-the-art methods is a plausible threat. In this paper we discuss algorithms and theoretical results that support the scalability of stealth mode overlays, and we present realistic simulations using an event based implementation of a proof-of-concept system. Besides P2P botnets, our results are also applicable in scenarios where relying on a large number of overlay connections per node is not feasible because of cost or the limited number of communication channels available.

  10. Unstructured P2P Network Load Balance Strategy Based on Multilevel Partitioning of Hypergraph

    Science.gov (United States)

    Feng, Lv; Chunlin, Gao; Kaiyang, Ma

    2017-05-01

    With rapid development of computer performance and distributed technology, P2P-based resource sharing mode plays important role in Internet. P2P network users continued to increase so the high dynamic characteristics of the system determine that it is difficult to obtain the load of other nodes. Therefore, a dynamic load balance strategy based on hypergraph is proposed in this article. The scheme develops from the idea of hypergraph theory in multilevel partitioning. It adopts optimized multilevel partitioning algorithms to partition P2P network into several small areas, and assigns each area a supernode for the management and load transferring of the nodes in this area. In the case of global scheduling is difficult to be achieved, the priority of a number of small range of load balancing can be ensured first. By the node load balance in each small area the whole network can achieve relative load balance. The experiments indicate that the load distribution of network nodes in our scheme is obviously compacter. It effectively solves the unbalanced problems in P2P network, which also improve the scalability and bandwidth utilization of system.

  11. Piloting a Sex-Specific, Technology-Enhanced, Active Learning Intervention for Stroke Prevention in Women.

    Science.gov (United States)

    Dirickson, Amanda; Stutzman, Sonja E; Alberts, Mark J; Novakovic, Roberta L; Stowe, Ann M; Beal, Claudia C; Goldberg, Mark P; Olson, DaiWai M

    2017-12-01

    Recent studies reveal deficiencies in stroke awareness and knowledge of risk factors among women. Existing stroke education interventions may not address common and sex-specific risk factors in the population with the highest stroke-related rate of mortality. This pilot study assessed the efficacy of a technology-enhanced, sex-specific educational program ("SISTERS") for women's knowledge of stroke. This was an experimental pretest-posttest design. The sample consisted of 150 women (mean age, 55 years) with at least 1 stroke risk factor. Participants were randomized to either the intervention (n = 75) or control (n = 75) group. Data were collected at baseline and at a 2-week posttest. There was no statistically significant difference in mean knowledge score (P = .67), mean confidence score (P = .77), or mean accuracy score (P = .75) between the intervention and control groups at posttest. Regression analysis revealed that older age was associated with lower knowledge scores (P women may have less comfort with technology and require consideration for cognitive differences.

  12. Detecting P2P Botnet in Software Defined Networks

    Directory of Open Access Journals (Sweden)

    Shang-Chiuan Su

    2018-01-01

    Full Text Available Software Defined Network separates the control plane from network equipment and has great advantage in network management as compared with traditional approaches. With this paradigm, the security issues persist to exist and could become even worse because of the flexibility on handling the packets. In this paper we propose an effective framework by integrating SDN and machine learning to detect and categorize P2P network traffics. This work provides experimental evidence showing that our approach can automatically analyze network traffic and flexibly change flow entries in OpenFlow switches through the SDN controller. This can effectively help the network administrators manage related security problems.

  13. Portable Ultraviolet Light Surface-Disinfecting Devices for Prevention of Hospital-Acquired Infections: A Health Technology Assessment

    Science.gov (United States)

    Nikitovic-Jokic, Milica; Kabali, Conrad; Li, Chunmei; Higgins, Caroline

    2018-01-01

    Background Hospital-acquired infections (HAIs) are infections that patients contract while in the hospital that were neither present nor developing at the time of admission. In Canada an estimated 10% of adults with short-term hospitalization have HAIs. According to 2003 Canadian data, between 4% and 6% of these patients die from these infections. The most common HAIs in Ontario are caused by Clostridium difficile. The standard method of reducing and preventing these infections is decontamination of patient rooms through manual cleaning and disinfection. Several portable no-touch ultraviolet (UV) light systems have been proposed to supplement current hospital cleaning and disinfecting practices. Methods We searched for studies published from inception of UV disinfection technology to January 23, 2017. We compared portable UV surface-disinfecting devices used together with standard hospital room cleaning and disinfecting versus standard hospital cleaning and disinfecting alone. The primary outcome was HAI from C. difficile. Other outcomes were combined HAIs, colonization (i.e., carrying an infectious agent without exhibiting disease symptoms), and the HAI-associated mortality rate. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to rate the quality of evidence of included studies. We also performed a 5-year budget impact analysis from the hospital's perspective. This assessment was limited to portable devices and did not examine wall mounted devices, which are used in some hospitals. Results The database search for the clinical review yielded 10 peer-reviewed publications that met eligibility criteria. Three studies focused on mercury UV-C–based technology, seven on pulsed xenon UV technology. Findings were either inconsistent or produced very low-quality evidence using the GRADE rating system. The intervention was effective in reducing the rate of the composite outcome of HAIs (combined) and colonization (but quality of evidence

  14. Portable Ultraviolet Light Surface-Disinfecting Devices for Prevention of Hospital-Acquired Infections: A Health Technology Assessment.

    Science.gov (United States)

    2018-01-01

    Hospital-acquired infections (HAIs) are infections that patients contract while in the hospital that were neither present nor developing at the time of admission. In Canada an estimated 10% of adults with short-term hospitalization have HAIs. According to 2003 Canadian data, between 4% and 6% of these patients die from these infections. The most common HAIs in Ontario are caused by Clostridium difficile . The standard method of reducing and preventing these infections is decontamination of patient rooms through manual cleaning and disinfection. Several portable no-touch ultraviolet (UV) light systems have been proposed to supplement current hospital cleaning and disinfecting practices. We searched for studies published from inception of UV disinfection technology to January 23, 2017. We compared portable UV surface-disinfecting devices used together with standard hospital room cleaning and disinfecting versus standard hospital cleaning and disinfecting alone. The primary outcome was HAI from C. difficile . Other outcomes were combined HAIs, colonization (i.e., carrying an infectious agent without exhibiting disease symptoms), and the HAI-associated mortality rate. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to rate the quality of evidence of included studies. We also performed a 5-year budget impact analysis from the hospital's perspective. This assessment was limited to portable devices and did not examine wall mounted devices, which are used in some hospitals. The database search for the clinical review yielded 10 peer-reviewed publications that met eligibility criteria. Three studies focused on mercury UV-C-based technology, seven on pulsed xenon UV technology. Findings were either inconsistent or produced very low-quality evidence using the GRADE rating system. The intervention was effective in reducing the rate of the composite outcome of HAIs (combined) and colonization (but quality of evidence was low). For the review

  15. Optimisiation of The Total Weighed Holding Time in A P2P Network

    Directory of Open Access Journals (Sweden)

    Naors Y Anad Alsaleem

    2017-02-01

    Full Text Available On the basis of working out of mathematical model in networks of peer-to-peer communication is that the formulation of a problem of optimisation of the total weighed holding time must be given. Optimization of the mathematical model constructed оn the theory of schedules. The common system decision is received, allowing to optimise a P2P network holding time. The practical importance is the described models and methods of the theory of schedules allow to display adequately the structure and the function of a P2P network and to consider their dynamics, restriction of previous information, shifts, interruptions and other typical technological decisions that can be used to increase the productivity of a network and quality of granting of services QoS, QoE

  16. Two Different Maintenance Strategies in the Hospital Environment: Preventive Maintenance for Older Technology Devices and Predictive Maintenance for Newer High-Tech Devices

    Science.gov (United States)

    Sezdi, Mana

    2016-01-01

    A maintenance program generated through the consideration of characteristics and failures of medical equipment is an important component of technology management. However, older technology devices and newer high-tech devices cannot be efficiently managed using the same strategies because of their different characteristics. This study aimed to generate a maintenance program comprising two different strategies to increase the efficiency of device management: preventive maintenance for older technology devices and predictive maintenance for newer high-tech devices. For preventive maintenance development, 589 older technology devices were subjected to performance verification and safety testing (PVST). For predictive maintenance development, the manufacturers' recommendations were used for 134 high-tech devices. These strategies were evaluated in terms of device reliability. This study recommends the use of two different maintenance strategies for old and new devices at hospitals in developing countries. Thus, older technology devices that applied only corrective maintenance will be included in maintenance like high-tech devices. PMID:27195666

  17. Two Different Maintenance Strategies in the Hospital Environment: Preventive Maintenance for Older Technology Devices and Predictive Maintenance for Newer High-Tech Devices.

    Science.gov (United States)

    Sezdi, Mana

    2016-01-01

    A maintenance program generated through the consideration of characteristics and failures of medical equipment is an important component of technology management. However, older technology devices and newer high-tech devices cannot be efficiently managed using the same strategies because of their different characteristics. This study aimed to generate a maintenance program comprising two different strategies to increase the efficiency of device management: preventive maintenance for older technology devices and predictive maintenance for newer high-tech devices. For preventive maintenance development, 589 older technology devices were subjected to performance verification and safety testing (PVST). For predictive maintenance development, the manufacturers' recommendations were used for 134 high-tech devices. These strategies were evaluated in terms of device reliability. This study recommends the use of two different maintenance strategies for old and new devices at hospitals in developing countries. Thus, older technology devices that applied only corrective maintenance will be included in maintenance like high-tech devices.

  18. Electron beam treatment technology for exhaust gas for preventing acid rain

    International Nuclear Information System (INIS)

    Aoki, Shinji

    1990-01-01

    Recently, accompanying the increase of the use of fossil fuel, the damage due to acid rain such as withering of trees and extinction of fishes and shells has occurred worldwide, and it has become a serious problem. The sulfur oxides and nitrogen oxides contained in exhaust gas are oxidized by the action of sunbeam to become sulfuric acid and nitric acid mists, which fall in the form of rain. Acid rain is closely related to the use of the coal containing high sulfur, and it hinders the use of coal which is rich energy source. In order to simplify the processing system for boiler exhaust gas and to reduce waste water and wastes, Ebara Corp. developed the dry simultaneous desulfurizing and denitrating technology utilizing electron beam in cooperation with Japan Atomic Energy Research Institute. The flow chart of the system applied to the exhaust gas treatment in a coal-fired thermal power station is shown. The mechanism of desulfurization and denitration, and the features of this system are described. The demonstration plant was constructed in a coal-fired thermal power station in Indianapolis, Indiana, USA, and the trial operation was completed in July, 1987. The test results are reported. (K.I.)

  19. Hospital adoption of automated surveillance technology and the implementation of infection prevention and control programs.

    Science.gov (United States)

    Halpin, Helen; Shortell, Stephen M; Milstein, Arnold; Vanneman, Megan

    2011-05-01

    This research analyzes the relationship between hospital use of automated surveillance technology (AST) for identification and control of hospital-acquired infections (HAI) and implementation of evidence-based infection control practices. Our hypothesis is that hospitals that use AST have made more progress implementing infection control practices than hospitals that rely on manual surveillance. A survey of all acute general care hospitals in California was conducted from October 2008 through January 2009. A structured computer-assisted telephone interview was conducted with the quality director of each hospital. The final sample includes 241 general acute care hospitals (response rate, 83%). Approximately one third (32.4%) of California's hospitals use AST for monitoring HAI. Adoption of AST is statistically significant and positively associated with the depth of implementation of evidence-based practices for methicillin-resistant Staphylococcus aureus and ventilator-associated pneumonia and adoption of contact precautions and surgical care infection practices. Use of AST is also statistically significantly associated with the breadth of hospital implementation of evidence-based practices across all 5 targeted HAI. Our findings suggest that hospitals using AST can achieve greater depth and breadth in implementing evidenced-based infection control practices. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  20. Study of the technology of heat pipe on prevention wildfire of coal gangue hill

    Science.gov (United States)

    Deng, Jun; Li, Bei; Ding, Ximei; Ma, Li

    2017-04-01

    Self-ignitable coal gangue hill (CGH) is one kind of special combustion system, which has the characteristics of low self-ignite point, large heat storage, and easy reignition. The currently industrial fire extinguishing methods, such as inhibiting tendency of coal self-ignition, loessial overburden, and cement grouting, had unsatisfied effects for dispersing the heat out in time. Correspondingly, the CGH will lead reignition more frequently with the passage of time. The high underground temperature of CGH threatens the process of ecological and vegetation construction. Therefore, the elimination of high temperature is a vital issue to be solved urgently for habitat restoration. To achieve the ultimately ecological management goal of self-ignitable CGH - extinguishing the fire completely and never reignited, it is crucial to break the heat accumulation. Heat-pipe (HP) has a character of high efficient heat transfer capacity for eliminating the continuously high temperature in CGH. An experimental system was designed to test the heat transfer performance of HP for preventing and extinguishing the spontaneous combustion of coal gangue. Based on the heat transfer theory, the resistance network of the coal-HP heat removal system was analyzed for studying the cooling effect of HP. The experimental results show that the HP can accelerate the heat release in coal gangue pile. The coal temperature could be controlled at 59.6 ˚ C with HP in 7 h and the highest cooling value is 39.4 % with HP in 150 h, which can effectively cool the temperatures of high temperature zones. As a powerful heat transfer components, as soon as HPs were inserted into the CGH with a reasonable distance, it can completely play a vital role in inhibiting the coal self-ignition process.

  1. Empowerment and new technologies. New challenges for the prevention and rehabilitation of addiction

    Directory of Open Access Journals (Sweden)

    Manuela Fabbri

    2009-07-01

    Full Text Available The concept of addiction is undergoing considerable evolution in meaning and now covers the phenomena of unbalanced and depersonalise relationships between the individual and a system of substances, other people and situations which are quite removed from traditional narcotic substances. Today we speak of addiction to the Internet, food, work and the market among others. In this context the historical association of addiction and deviance is missing and in a reality where everyone is at risk of developing addictions, the focus of intervention have been moved from therapeutic-rehabilitative action to prevention. Starting out with a brief analysis of this new situation, this article describes a pedagogical course of action from an empowerment prospective which is able to stimulate the capacity for self-help in cases of serious addiction, but before reaching this stage, anticipating, taking strength from individual and social qualities in one’s existential styling. A project of this nature requires the activation of a network of relationships to accompany the subject in his or her choices, to construct that rich proximal environment within which the individual can develop autonomy and the capacity for supporting oneself. The new tools of communication that characterise the so called “knowledge society potentially represent as many tools for the qualification of communication itself in the direction of empowerment. In the current social reality these are revealed mainly as producers of high risk toxic depersonalisation and as stimulators of situations fro new addiction. In theory and in some experimental practices we can and should project a use for the development of the individual and the community.

  2. P2X7 receptors in satellite glial cells mediate high functional expression of P2X3 receptors in immature dorsal root ganglion neurons

    Directory of Open Access Journals (Sweden)

    Chen Yong

    2012-02-01

    Full Text Available Abstract Background The purinergic P2X3 receptor (P2X3R expressed in the dorsal root ganglion (DRG sensory neuron and the P2X7 receptor (P2X7R expressed in the surrounding satellite glial cell (SGC are two major receptors participating in neuron-SGC communication in adult DRGs. Activation of P2X7Rs was found to tonically reduce the expression of P2X3Rs in DRGs, thus inhibiting the abnormal pain behaviors in adult rats. P2X receptors are also actively involved in sensory signaling in developing rodents. However, very little is known about the developmental change of P2X7Rs in DRGs and the interaction between P2X7Rs and P2X3Rs in those animals. We therefore examined the expression of P2X3Rs and P2X7Rs in postnatal rats and determined if P2X7R-P2X3R control exists in developing rats. Findings We immunostained DRGs of immature rats and found that P2X3Rs were expressed only in neurons and P2X7Rs were expressed only in SGCs. Western blot analyses indicated that P2X3R expression decreased while P2X7R expression increased with the age of rats. Electrophysiological studies showed that the number of DRG neurons responding to the stimulation of the P2XR agonist, α,β-meATP, was higher and the amplitudes of α,β-meATP-induced depolarizations were larger in immature DRG neurons. As a result, P2X3R-mediated flinching responses were much more pronounced in immature rats than those found in adult rats. When we reduced P2X7R expression with P2X7R-siRNA in postnatal and adult rats, P2X3R-mediated flinch responses were greatly enhanced in both rat populations. Conclusions These results show that the P2X7R expression increases as rats age. In addition, P2X7Rs in SGCs exert inhibitory control on the P2X3R expression and function in sensory neurons of immature rats, just as observed in adult rats. Regulation of P2X7R expression is likely an effective way to control P2X3R activity and manage pain relief in infants.

  3. Parameterization-based tracking for the P2 experiment

    Science.gov (United States)

    Sorokin, Iurii

    2017-08-01

    The P2 experiment in Mainz aims to determine the weak mixing angle θW at low momentum transfer by measuring the parity-violating asymmetry of elastic electronproton scattering. In order to achieve the intended precision of Δ(sin2 θW)/sin2θW = 0:13% within the planned 10 000 hours of running the experiment has to operate at the rate of 1011 detected electrons per second. Although it is not required to measure the kinematic parameters of each individual electron, every attempt is made to achieve the highest possible throughput in the track reconstruction chain. In the present work a parameterization-based track reconstruction method is described. It is a variation of track following, where the results of the computation-heavy steps, namely the propagation of a track to the further detector plane, and the fitting, are pre-calculated, and expressed in terms of parametric analytic functions. This makes the algorithm extremely fast, and well-suited for an implementation on an FPGA. The method also takes implicitly into account the actual phase space distribution of the tracks already at the stage of candidate construction. Compared to a simple algorithm, that does not use such information, this allows reducing the combinatorial background by many orders of magnitude, down to O(1) background candidate per one signal track. The method is developed specifically for the P2 experiment in Mainz, and the presented implementation is tightly coupled to the experimental conditions.

  4. Decrease of serum adenine nucleotide hydrolysis in an irritant contact dermatitis mice model: potential P2X7R involvement.

    Science.gov (United States)

    Zanin, R F; da Silva, G L; Erig, T; Sperotto, N D M; Leite, C E; Coutinho-Silva, R; Batastini, A M O; Morrone, Fernanda Bueno

    2015-06-01

    Extracellular adenosine 5'-triphosphate (ATP) has significant effects on a variety of pathological conditions and it is the main physiological agonist of P2X7 purinergic receptor (P2X7R). It is known that ATP acting via purinergic receptors plays a relevant role on skin inflammation, and P2X7R is required to neutrophil recruitment in a mice model of irritant contact dermatitis (ICD).The present study investigated the effects of chemical irritant croton oil (CrO) upon ATP, ADP, and AMP hydrolysis in mice blood serum, and the potential involvement of P2X7R. The topical application CrO induced a decrease on soluble ATP/ADPase activities (~50 %), and the treatment with the selective P2X7R antagonist, A438079, reversed these effects to control level. Furthermore, we showed that CrO decreased cellular viability (52.6 % ± 3.9) in relation to the control and caused necrosis in keratinocytes (PI positive cells). The necrosis induced by CrO was prevented by the pre-treatment with the selective P2X7R antagonist A438079. The results presented herein suggest that CrO exerts an inhibitory effect on the activity of ATPDase in mouse serum, reinforcing the idea that ICD has a pathogenic mechanism dependent of CD39. Furthermore, it is tempting to suggest that P2X7R may act as a controller of the extracellular levels of ATP.

  5. Wastewater treatment technologies to satisfy 1990's energy conservation/pollution prevention goals

    International Nuclear Information System (INIS)

    Keith, L.W.; Beers, A.R.

    1993-01-01

    Anheuser-Busch, like most other companies, relied through the mid-1970's on end-of-pipe, energy-intensive aerobic treatment systems for its wastewater. Little if any attention was placed on source reduction. There are several factors that help explain why industry had adopted this approach. Energy was relatively cheap, sludge disposal was not a major problem and many municipalities provided wastewater treatment capacity to industry as an inducement for industry to locate there. The saying for A-B was open-quotes We know how to make beer - municipalities know how to treat our wastewater - let's not mix the two.close quotes The 1973 oil embargo and the resulting mid-1970's energy crisis changed Anheuser-Busch's wastewater treatment philosophy. The days of cheap energy and wastewater treatment were gone. This was only exaggerated by the more stringent treatment requirements resulting from the passage of PL92-500 (Clean Water Act). Increasing sludge disposal problems with associated increased disposal costs also occurred. From the mid-1970's to the mid-1980's Anheuser-Busch performed significant developmental work on land application of wastewater. This technology, which requires only about 10% of the energy of aerobic activated sludge treatment systems and produces no sludge for disposal, was installed at six Anheuser-Busch locations. During this time period considerable improvement was made in the area of waste load reduction. However, the main driving force was economics; that is, it was done if cheaper than wastewater treatment. Anheuser-Busch still had a basic end-of-pipe treatment philosophy

  6. Re-use of wastewater: preventing the recovery of pathogens by using medium-pressure UV lamp technology.

    Science.gov (United States)

    Kalisvaart, B F

    2004-01-01

    Ultraviolet (UV) light has become widely accepted as an alternative to chlorination or ozonation for wastewater disinfection. There are now over 2,000 wastewater treatment plants worldwide using either low- or medium-pressure UV technology. Recent studies investigating UV lamp technology, configuration, cleaning requirements and ageing, as well as long-term performance tests, have demonstrated beyond any doubt the effectiveness of UV in inactivating pathogens in wastewater. Research has also shown that, to ensure permanent inactivation and prevent the recovery of microorganisms following exposure to UV, a broad, "polychromatic" spectrum of UV wavelengths is necessary. These wavelengths inflict irreparable damage not only on cellular DNA, but on other molecules, such as enzymes, as well. Only medium-pressure UV lamps produce the necessary broad range of wavelengths; low-pressure lamps emit a single wavelength peak which only affects DNA. Polychromatic medium-pressure UV light is so effective because of the lamp's exceptionally high UV energy output at specific wavelengths across the UV spectrum. It has been shown, for example, that pathogenic E. coli O175:H7 was able to repair the damage caused by low-pressure UV, but no repair was detected following exposure to UV from medium-pressure lamps.

  7. Nanomedicine and advanced technologies for burns: Preventing infection and facilitating wound healing.

    Science.gov (United States)

    Mofazzal Jahromi, Mirza Ali; Sahandi Zangabad, Parham; Moosavi Basri, Seyed Masoud; Sahandi Zangabad, Keyvan; Ghamarypour, Ameneh; Aref, Amir R; Karimi, Mahdi; Hamblin, Michael R

    2018-01-01

    According to the latest report from the World Health Organization, an estimated 265,000 deaths still occur every year as a direct result of burn injuries. A widespread range of these deaths induced by burn wound happens in low- and middle-income countries, where survivors face a lifetime of morbidity. Most of the deaths occur due to infections when a high percentage of the external regions of the body area is affected. Microbial nutrient availability, skin barrier disruption, and vascular supply destruction in burn injuries as well as systemic immunosuppression are important parameters that cause burns to be susceptible to infections. Topical antimicrobials and dressings are generally employed to inhibit burn infections followed by a burn wound therapy, because systemic antibiotics have problems in reaching the infected site, coupled with increasing microbial drug resistance. Nanotechnology has provided a range of molecular designed nanostructures (NS) that can be used in both therapeutic and diagnostic applications in burns. These NSs can be divided into organic and non-organic (such as polymeric nanoparticles (NPs) and silver NPs, respectively), and many have been designed to display multifunctional activity. The present review covers the physiology of skin, burn classification, burn wound pathogenesis, animal models of burn wound infection, and various topical therapeutic approaches designed to combat infection and stimulate healing. These include biological based approaches (e.g. immune-based antimicrobial molecules, therapeutic microorganisms, antimicrobial agents, etc.), antimicrobial photo- and ultrasound-therapy, as well as nanotechnology-based wound healing approaches as a revolutionizing area. Thus, we focus on organic and non-organic NSs designed to deliver growth factors to burned skin, and scaffolds, dressings, etc. for exogenous stem cells to aid skin regeneration. Eventually, recent breakthroughs and technologies with substantial potentials in tissue

  8. Adaptive Streaming of Scalable Videos over P2PTV

    Directory of Open Access Journals (Sweden)

    Youssef Lahbabi

    2015-01-01

    Full Text Available In this paper, we propose a new Scalable Video Coding (SVC quality-adaptive peer-to-peer television (P2PTV system executed at the peers and at the network. The quality adaptation mechanisms are developed as follows: on one hand, the Layer Level Initialization (LLI is used for adapting the video quality with the static resources at the peers in order to avoid long startup times. On the other hand, the Layer Level Adjustment (LLA is invoked periodically to adjust the SVC layer to the fluctuation of the network conditions with the aim of predicting the possible stalls before their occurrence. Our results demonstrate that our mechanisms allow quickly adapting the video quality to various system changes while providing best Quality of Experience (QoE that matches current resources of the peer devices and instantaneous throughput available at the network state.

  9. The P2X7 receptor regulates cell survival, migration and invasion of pancreatic ductal adenocarcinoma cells.

    Science.gov (United States)

    Giannuzzo, Andrea; Pedersen, Stine Falsig; Novak, Ivana

    2015-11-25

    Pancreatic ductal adenocarcinoma (PDAC) is presently one of the cancers with the worst survival rates and least effective treatments. Moreover, total deaths due to PDAC are predicted to increase in the next 15 years. Therefore, novel insights into basic mechanism of PDAC development and therapies are needed. PDAC is characterized by a complex microenvironment, in which cancer and stromal cells release different molecules, such as ATP. ATP can be transported and/or exocytosed from active cancer cells and released from dying cells in the necrotic core of the cancer. We hypothesized that one of the ATP receptors, the P2X7 receptor (P2X7R) could be an important player in PDAC behaviour. We determined the expression (real time PCR and Western blot) and localization (immunofluorescence) of P2X7R in human PDAC cell lines (AsPC-1, BxPC-3, Capan-1, MiaPaCa-2, Panc-1) and a "normal" human pancreatic duct epithelial cell line (HPDE). The function of P2X7R in proliferation (BrdU assay), migration (wound assay) and invasion (Boyden chamber with matrigel) was characterized. Furthermore, we studied P2X7R-dependent pore formation (YoPro-1 assay) and cell death (caspase and annexin V / propidium iodide assays). We found higher expression of P2X7R protein in PDAC compared to HPDE cells. P2X7R had notable disparate effects on PDAC survival. Firstly, high concentrations of ATP or the specific P2X7R agonist, BzATP, had cytotoxic effects in all cell lines, and cell death was mediated by necrosis. Moreover, the P2X7R-pore antagonist, A438079, prevented ATP-induced pore formation and cell death. Second, in basal conditions and with low concentrations of ATP/BzATP, the P2X7R allosteric inhibitor AZ10606120 reduced proliferation in all PDAC cell lines. P2X7R also affected other key characteristics of cancer cell behavior. AZ10606120 reduced cell migration and invasion in PDAC cell lines compared to that of untreated/vehicle-treated control cells, and stimulation with sub

  10. A P2P Service Discovery Strategy Based on Content Catalogues

    Directory of Open Access Journals (Sweden)

    Lican Huang

    2007-08-01

    Full Text Available This paper presents a framework for distributed service discovery based on VIRGO P2P technologies. The services are classified as multi-layer, hierarchical catalogue domains according to their contents. The service providers, which have their own service registries such as UDDIs, register the services they provide and establish a virtual tree in a VIRGO network according to the domain of their service. The service location done by the proposed strategy is effective and guaranteed. This paper also discusses the primary implementation of service discovery based on Tomcat/Axis and jUDDI.

  11. The Measurement and Modeling of a P2P Streaming Video Service

    Science.gov (United States)

    Gao, Peng; Liu, Tao; Chen, Yanming; Wu, Xingyao; El-Khatib, Yehia; Edwards, Christopher

    Most of the work on grid technology in video area has been generally restricted to aspects of resource scheduling and replica management. The traffic of such service has a lot of characteristics in common with that of the traditional video service. However the architecture and user behavior in Grid networks are quite different from those of traditional Internet. Considering the potential of grid networks and video sharing services, measuring and analyzing P2P IPTV traffic are important and fundamental works in the field grid networks.

  12. Two Different Maintenance Strategies in the Hospital Environment: Preventive Maintenance for Older Technology Devices and Predictive Maintenance for Newer High-Tech Devices

    OpenAIRE

    Sezdi, Mana

    2016-01-01

    A maintenance program generated through the consideration of characteristics and failures of medical equipment is an important component of technology management. However, older technology devices and newer high-tech devices cannot be efficiently managed using the same strategies because of their different characteristics. This study aimed to generate a maintenance program comprising two different strategies to increase the efficiency of device management: preventive maintenance for older tec...

  13. C/2013 P2 Pan STARRS - The Manx Comet

    Science.gov (United States)

    Meech, Karen J.; Yang, Bin; Keane, Jacqueline; Hainaut, Olivier; Kleyna, Jan; Hsieh, Henry; Bauer, James; Wainscoat, Richard; Veres, Peter

    2014-11-01

    On Aug 4, 2013 an apparently asteroidal object was discovered by the Pan STARRS1 (PS1) survey telescope on Haleakala at magnitude 20.4 (corresponding to a nucleus radius between 1.4-2.9 km for albedos between 0.25-0.04). PS1 pre-recovery images taken on July 26 and on Aug. 3 allowed a good orbit to be determined. The orbit looks like that of a long-period comet with a semi major axis of 2720 AU and an eccentricity of 0.999. Shortly following the discovery, reports from small telescopes came in that there was low level activity associated with this object (at r = 3.45 AU), and the object was designated P/2013 P2 (Pan STARRS). The activity was not seen in images obtained with PS1, the Faulkes N telescope or the CFHT 3.6m, however the object was passing through a region of significant nebulosity. Deep images obtained on the CFHT on Aug. 8 and follow up images obtained with the Gemini North 8m telescope on Sep. 9 showed a very faint tail extending a few arcsec to PA=45 deg (inconsistent with the earlier reports). The object was observed using several facilities up until solar conjunction, and again after perihelion (Feb. 17, 2014) in March, with little increase in activity. A search of the NEOWISE archives show no detection during the cryogenic and immediate pos-cryogenic phases, so we can only place an upper limit on the nucleus size from these data. An object on a long-period comet orbit at this heliocentric distance typically should be very active, and our team hypothesized that this could either be a nearly-extinct comet or possibly inner solar system material ejected to the outer solar system during planet migration as predicted by various dynamical models. To distinguish between these scenarios, we obtained both optical and near-IR spectra of P/2013 P2 on 2014 May 7 and 21, when the object was at r=2.97 and 2.99 AU, respectively. Initial reductions show no emission lines. We will report on our spectra and imaging data, and discuss the implications for the origin

  14. Digital technology for treating and preventing mental disorders in low-income and middle-income countries: a narrative review of the literature.

    Science.gov (United States)

    Naslund, John A; Aschbrenner, Kelly A; Araya, Ricardo; Marsch, Lisa A; Unützer, Jürgen; Patel, Vikram; Bartels, Stephen J

    2017-06-01

    Few individuals living with mental disorders around the globe have access to mental health care, yet most have access to a mobile phone. Digital technology holds promise for improving access to, and quality of, mental health care. We reviewed evidence on the use of mobile, online, and other remote technologies for treatment and prevention of mental disorders in low-income and middle-income countries. Of the 49 studies identified, most were preliminary evaluations of feasibility and acceptability. The findings were promising, showing the potential effectiveness of online, text-messaging, and telephone support interventions. We summarised the evaluations as: technology for supporting clinical care and educating health workers, mobile tools for facilitating diagnosis and detection of mental disorders, technologies for promoting treatment adherence and supporting recovery, online self-help programmes for individuals with mental disorders, and programmes for substance misuse prevention and treatment. Continued research is needed to rigorously evaluate effectiveness, assess costs, and carefully consider potential risks of digital technology interventions for mental disorders, while determining how emerging technologies might support the scale-up of mental health treatment and prevention efforts across low-resource settings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Opposing Roles of Calcium and Intracellular ATP on Gating of the Purinergic P2X2 Receptor Channel

    Directory of Open Access Journals (Sweden)

    Milos B. Rokic

    2018-04-01

    Full Text Available P2X2 receptors (P2X2R exhibit a slow desensitization during the initial ATP application and a progressive, calcium-dependent increase in rates of desensitization during repetitive stimulation. This pattern is observed in whole-cell recordings from cells expressing recombinant and native P2X2R. However, desensitization is not observed in perforated-patched cells and in two-electrode voltage clamped oocytes. Addition of ATP, but not ATPγS or GTP, in the pipette solution also abolishes progressive desensitization, whereas intracellular injection of apyrase facilitates receptor desensitization. Experiments with injection of alkaline phosphatase or addition of staurosporine and ATP in the intracellular solution suggest a role for a phosphorylation-dephosphorylation in receptor desensitization. Mutation of residues that are potential phosphorylation sites identified a critical role of the S363 residue in the intracellular ATP action. These findings indicate that intracellular calcium and ATP have opposing effects on P2X2R gating: calcium allosterically facilitates receptor desensitization and ATP covalently prevents the action of calcium. Single cell measurements further revealed that intracellular calcium stays elevated after washout in P2X2R-expressing cells and the blockade of mitochondrial sodium/calcium exchanger lowers calcium concentrations during washout periods to basal levels, suggesting a role of mitochondria in this process. Therefore, the metabolic state of the cell can influence P2X2R gating.

  16. Mobile phone technology: a new paradigm for the prevention, treatment, and research of the non-sheltered "street" homeless?

    Science.gov (United States)

    Eyrich-Garg, Karin M

    2010-05-01

    Individuals experiencing homelessness have disproportionately high rates of health problems. Those who perceive themselves as having greater access to their social support networks have better physical and mental health outcomes as well as lower rates of victimization. Mobile phones offer a connection to others without the physical constraints of landlines and, therefore, may make communication (e.g., access to one's social support networks) more feasible for homeless individuals. This, in turn, could lead toward better health outcomes. This exploratory study examined mobile phone possession and use among a sample of 100 homeless men and women who do not use the shelter system in Philadelphia, PA. Interviews were comprised of the Homeless Supplement to the Diagnostic Interview Schedule, a technology module created for this investigation, and the substance use and psychiatric sections of the Addiction Severity Index. Almost half (44%) of the sample had a mobile phone. In the past 30 days, 100% of those with mobile phones placed or received a call, over half (61%) sent or received a text message, and one fifth (20%) accessed the Internet via their mobile phone. Participants possessed and used mobile phones to increase their sense of safety, responsibility (employment, stable housing, personal business, and sobriety or "clean time"), and social connectedness. Mobile phones could potentially be used by public health/health care providers to disseminate information to the street homeless, to enhance communication between the street homeless and providers, and to increase access for the street homeless to prevention, intervention, and aftercare services. Finally, this technology could also be used by researchers to collect data with this transient population.

  17. Improved Degree Search Algorithms in Unstructured P2P Networks

    Directory of Open Access Journals (Sweden)

    Guole Liu

    2012-01-01

    Full Text Available Searching and retrieving the demanded correct information is one important problem in networks; especially, designing an efficient search algorithm is a key challenge in unstructured peer-to-peer (P2P networks. Breadth-first search (BFS and depth-first search (DFS are the current two typical search methods. BFS-based algorithms show the perfect performance in the aspect of search success rate of network resources, while bringing the huge search messages. On the contrary, DFS-based algorithms reduce the search message quantity and also cause the dropping of search success ratio. To address the problem that only one of performances is excellent, we propose two memory function degree search algorithms: memory function maximum degree algorithm (MD and memory function preference degree algorithm (PD. We study their performance including the search success rate and the search message quantity in different networks, which are scale-free networks, random graph networks, and small-world networks. Simulations show that the two performances are both excellent at the same time, and the performances are improved at least 10 times.

  18. Synthesis and Potency of Novel Uracil Nucleotides and Derivatives as P2Y2 and P2Y6 Receptor Agonists

    OpenAIRE

    Ko, Hyojin; Carter, Rhonda L.; Cosyn, Liesbet; Petrelli, Riccardo; de Castro, Sonia; Besada, Pedro; Zhou, Yixing; Cappellacci, Loredana; Franchetti, Palmarisa; Grifantini, Mario; Van Calenbergh, Serge; Harden, T. Kendall; Jacobson, Kenneth A.

    2008-01-01

    The phosphate, uracil, and ribose moieties of uracil nucleotides were varied structurally for evaluation of agonist activity at the human P2Y2, P2Y4, and P2Y6 receptors. The 2-thio modification, found previously to enhance P2Y2 receptor potency, could be combined with other favorable modifications to produce novel molecules that exhibit high potencies and receptor selectivities. Phosphonomethylene bridges introduced for stability in analogues of UDP, UTP and uracil dinucleotides markedly redu...

  19. Wearable cardioverter defibrillators for the prevention of sudden cardiac arrest: a health technology assessment and patient focus group study

    Directory of Open Access Journals (Sweden)

    Ettinger S

    2017-11-01

    Full Text Available Sabine Ettinger,1 Michal Stanak,1 Piotr Szymański,2 Claudia Wild,1 Romana Tandara Haček,3 Darija Erčević,3 Renata Grenković,3 Mirjana Huić3 1Ludwig Boltzmann Institute for Health Technology Assessment, Vienna, Austria; 2Institute of Cardiology, Warsaw, Poland; 3Department for Development, Research and Health Technology Assessment, Agency for Quality and Accreditation in Health Care and Social Welfare, Zagreb, Croatia Aim: To summarize the evidence on clinical effectiveness and safety of wearable cardioverter defibrillator (WCD therapy for primary and secondary prevention of sudden cardiac arrest in patients at risk. Methods: We performed a systematic literature search in databases including MEDLINE via OVID, Embase, the Cochrane Library, and CRD (DARE, NHS-EED, HTA. The evidence obtained was summarized according to GRADE methodology. A health technology assessment (HTA was conducted using the HTA Core Model® for rapid relative effectiveness assessment. Primary outcomes for the clinical effectiveness domain were all-cause and disease-specific mortality. Outcomes for the safety domain were adverse events (AEs and serious adverse events (SAEs. A focus group with cardiac disease patients was conducted to evaluate ethical, organizational, patient, social, and legal aspects of the WCD use. Results: No randomized- or non-randomized controlled trials were identified. Non-comparative studies (n=5 reported AEs including skin rash/itching (6%, false alarms (14%, and palpitations/light-headedness/fainting (9% and discontinuation due to comfort/lifestyle issues (16–22%, and SAEs including inappropriate shocks (0–2%, unsuccessful shocks (0–0.7%, and death (0–0.3%. The focus group results reported that experiencing a sense of security is crucial to patients and that the WCD is not considered an option for weeks or even months due to expected restrictions in living a “normal” life. Conclusion: The WCD appears to be relatively safe for short

  20. Peripheral nerve P2 basic protein and the Guillain-Barre syndrome : In vitro demonstration of P2-specific antibody-secreting cells

    NARCIS (Netherlands)

    Luijten, J.A.F.M.; Jong, W.A.C. de; Demel, R.A.; Heijnen, C.J.; Ballieux, R.E.

    1984-01-01

    An immune response to the peripheral nerve basic protein P2 may be operative in the pathogenesis of the Guillain-Barré syndrome (GBS). A method is described for the purification of P2 of human origin. Purified P2 was used to investigate whether lymphocytes derived from peripheral blood of GBS

  1. A potential therapeutic role for P2X7 receptor (P2X7R) antagonists in the treatment of inflammatory diseases.

    Science.gov (United States)

    Arulkumaran, Nishkantha; Unwin, Robert J; Tam, Frederick Wk

    2011-07-01

    The P2X7 receptor (P2X7R) has an important role in inflammation and immunity, but until recently, clinical application has been limited by a lack of specific antagonists. Recent studies using P2X7R knockout mice and specific receptor antagonists have shown that the P2X7R is an important therapeutic target in inflammatory diseases. We have reviewed the current literature on the role of the P2X7R in inflammatory diseases, focusing on potential therapeutic applications of selective P2X7R antagonists as anti-inflammatory agents. Particular emphasis has been placed on the potential role of P2X7R in common inflammatory diseases. The latest developments in Phase I and II clinical trials of P2X7R antagonists are covered. Recent studies using gene knockout mice and selective P2X7R antagonists suggest that P2X7R is a viable therapeutic target for inflammatory diseases. However, efficacious P2X7R antagonists for use in clinical studies are still at an early stage of development. Future challenges include: identifying potential toxicity and side effects of treatment, timing of treatment initiation and its duration in chronic inflammatory conditions, optimum dosage and development of a functional assay for P2X7R that would help to guide treatment.

  2. Double P2X2/P2X3 Purinergic Receptor Knockout Mice Do Not Taste NaCl or the Artificial Sweetener SC45647

    Science.gov (United States)

    Eddy, Meghan C.; Eschle, Benjamin K.; Barrows, Jennell; Hallock, Robert M.; Finger, Thomas E.

    2009-01-01

    The P2X ionotropic purinergic receptors, P2X2 and P2X3, are essential for transmission of taste information from taste buds to the gustatory nerves. Mice lacking both P2X2 and P2X3 purinergic receptors (P2X2/P2X3Dbl−/−) exhibit no taste-evoked activity in the chorda tympani and glossopharyngeal nerves when stimulated with taste stimuli from any of the 5 classical taste quality groups (salt, sweet, sour, bitter, and umami) nor do the mice show taste preferences for sweet or umami, or avoidance of bitter substances (Finger et al. 2005. ATP signaling is crucial for communication from taste buds to gustatory nerves. Science. 310[5753]:1495–1499). Here, we compare the ability of P2X2/P2X3Dbl−/− mice and P2X2/P2X3Dbl+/+ wild-type (WT) mice to detect NaCl in brief-access tests and conditioned aversion paradigms. Brief-access testing with NaCl revealed that whereas WT mice decrease licking at 300 mM and above, the P2X2/P2X3Dbl−/− mice do not show any change in lick rates. In conditioned aversion tests, P2X2/P2X3Dbl−/− mice did not develop a learned aversion to NaCl or the artificial sweetener SC45647, both of which are easily avoided by conditioned WT mice. The inability of P2X2/P2X3Dbl−/− mice to show avoidance of these taste stimuli was not due to an inability to learn the task because both WT and P2X2/P2X3Dbl−/− mice learned to avoid a combination of SC45647 and amyl acetate (an odor cue). These data suggest that P2X2/P2X3Dbl−/− mice are unable to respond to NaCl or SC45647 as taste stimuli, mirroring the lack of gustatory nerve responses to these substances. PMID:19833661

  3. Role of spinal P2Y6 and P2Y11 receptors in neuropathic pain in rats: possible involvement of glial cells

    OpenAIRE

    Barragán-Iglesias, Paulino; Pineda-Farias, Jorge Baruch; Cervantes-Durán, Claudia; Bravo-Hernández, Mariana; Rocha-González, Héctor Isaac; Murbartián, Janet; Granados-Soto, Vinicio

    2014-01-01

    Background The participation of spinal P2X receptors in neuropathic pain is well recognized. However, the role of P2Y receptors has been less studied. The purpose of this study was to investigate the contribution of spinal P2Y6,11 receptors following peripheral nerve damage induced by spinal nerve ligation. In addition, we determined the expression of P2Y6,11 receptors in the dorsal spinal cord in presence of the selective P2Y6,11 receptors antagonists. Furthermore, we evaluated the participa...

  4. Designed Incident Reporting System in P2TKN BATAN

    International Nuclear Information System (INIS)

    Supriatna, Piping; Sudarsyamsu S; Bambang S; Karyana, Edy

    2000-01-01

    Incident Reporting System is a routine activating for record all incident of Nuclear Plant Characteristic of the incident Reporting System (IRS) recording can be made locally, regionally or national scope. IRS recording of nuclear activity responsible to Nuclear Safety Technology Development Center (NSTDC). In this report has been designed IRS for nuclear incident in Batan, which the socialization in the field will be done step by step. The first step will be applied in NSTCD scope, the second step will be applied in PPTA Serpong area, and the third step will be applied in Batan area

  5. 4-Alkyloxyimino derivatives of uridine-5'-triphosphate: distal modification of potent agonists as a strategy for molecular probes of P2Y2, P2Y4, and P2Y6 receptors.

    Science.gov (United States)

    Jayasekara, P Suresh; Barrett, Matthew O; Ball, Christopher B; Brown, Kyle A; Hammes, Eva; Balasubramanian, Ramachandran; Harden, T Kendall; Jacobson, Kenneth A

    2014-05-08

    Extended N(4)-(3-arylpropyl)oxy derivatives of uridine-5'-triphosphate were synthesized and potently stimulated phospholipase C stimulation in astrocytoma cells expressing G protein-coupled human (h) P2Y receptors (P2YRs) activated by UTP (P2Y2/4R) or UDP (P2Y6R). The potent P2Y4R-selective N(4)-(3-phenylpropyl)oxy agonist was phenyl ring-substituted or replaced with terminal heterocyclic or naphthyl rings with retention of P2YR potency. This broad tolerance for steric bulk in a distal region was not observed for dinucleoside tetraphosphate agonists with both nucleobases substituted. The potent N(4)-(3-(4-methoxyphenyl)-propyl)oxy analogue 19 (EC50: P2Y2R, 47 nM; P2Y4R, 23 nM) was functionalized for chain extension using click tethering of fluorophores as prosthetic groups. The BODIPY 630/650 conjugate 28 (MRS4162) exhibited EC50 values of 70, 66, and 23 nM at the hP2Y2/4/6Rs, respectively, and specifically labeled cells expressing the P2Y6R. Thus, an extended N(4)-(3-arylpropyl)oxy group accessed a structurally permissive region on three Gq-coupled P2YRs, and potency and selectivity were modulated by distal structural changes. This freedom of substitution was utilized to design of a pan-agonist fluorescent probe of a subset of uracil nucleotide-activated hP2YRs.

  6. Current and Future Challenges in Point-of-Care Technologies: A Paradigm-Shift in Affordable Global Healthcare With Personalized and Preventive Medicine.

    Science.gov (United States)

    Dhawan, Atam P; Heetderks, William J; Pavel, Misha; Acharya, Soumyadipta; Akay, Metin; Mairal, Anurag; Wheeler, Bruce; Dacso, Clifford C; Sunder, T; Lovell, Nigel; Gerber, Martin; Shah, Milind; Senthilvel, S G; Wang, May D; Bhargava, Balram

    2015-01-01

    This paper summarizes the panel discussion at the IEEE Engineering in Medicine and Biology Point-of-Care Healthcare Technology Conference (POCHT 2013) held in Bangalore India from Jan 16-18, 2013. Modern medicine has witnessed interdisciplinary technology innovations in healthcare with a continuous growth in life expectancy across the globe. However, there is also a growing global concern on the affordability of rapidly rising healthcare costs. To provide quality healthcare at reasonable costs, there has to be a convergence of preventive, personalized, and precision medicine with the help of technology innovations across the entire spectrum of point-of-care (POC) to critical care at hospitals. The first IEEE EMBS Special Topic POCHT conference held in Bangalore, India provided an international forum with clinicians, healthcare providers, industry experts, innovators, researchers, and students to define clinical needs and technology solutions toward commercialization and translation to clinical applications across different environments and infrastructures. This paper presents a summary of discussions that took place during the keynote presentations, panel discussions, and breakout sessions on needs, challenges, and technology innovations in POC technologies toward improving global healthcare. Also presented is an overview of challenges and trends in developing and developed economies with respect to priority clinical needs, technology innovations in medical devices, translational engineering, information and communication technologies, infrastructure support, and patient and clinician acceptance of POC healthcare technologies.

  7. Action of Natural Products on P2 Receptors: A Reinvented Era for Drug Discovery

    Directory of Open Access Journals (Sweden)

    Luiz Alves

    2012-11-01

    Full Text Available Natural products contribute significantly to available drug therapies and have been a rich source for scientific investigation. In general, due to their low cost and traditional use in some cultures, they are an object of growing interest as alternatives to synthetic drugs. With several diseases such as cancer, and inflammatory and neuropathic diseases having been linked to the participation of purinergic (P2 receptors, there has been a flurry of investigations on ligands within natural products. Thirty-four different sources of these compounds have been found so far, that have shown either agonistic or antagonistic effects on P2 receptors. Of those, nine different plant sources demonstrated effects on P2X2, P2X3, P2X7, and possibly P2Y12 receptor subtypes. Microorganisms, which represent the largest group, with 26 different sources, showed effects on both receptor subtypes, ranging from P2X1 to P2X4 and P2X7, and P2Y1, P2Y2, P2Y4, and P2Y6. In addition, there were seventeen animal sources that affected P2X7 and P2Y1 and P2Y12 receptors. Natural products have provided some fascinating new mechanisms and sources to better understand the P2 receptor antagonism. Moreover, current investigations should clarify further pharmacological mechanisms in order to consider these products as potential new medicines.

  8. Role of spinal P2Y6 and P2Y11 receptors in neuropathic pain in rats: possible involvement of glial cells.

    Science.gov (United States)

    Barragán-Iglesias, Paulino; Pineda-Farias, Jorge Baruch; Cervantes-Durán, Claudia; Bravo-Hernández, Mariana; Rocha-González, Héctor Isaac; Murbartián, Janet; Granados-Soto, Vinicio

    2014-05-20

    The participation of spinal P2X receptors in neuropathic pain is well recognized. However, the role of P2Y receptors has been less studied. The purpose of this study was to investigate the contribution of spinal P2Y6,11 receptors following peripheral nerve damage induced by spinal nerve ligation. In addition, we determined the expression of P2Y6,11 receptors in the dorsal spinal cord in presence of the selective P2Y6,11 receptors antagonists. Furthermore, we evaluated the participation of spinal microglia and astrocytes in the pronociceptive role of P2Y6,11 receptors. Spinal administration of the selective P2Y6 (MRS2578, 10-100 μM) and P2Y11 (NF340, 0.3-30 μM) receptor antagonists reduced tactile allodynia in spinal nerve ligated rats. Nerve injury increased the expression of P2Y6,11 receptors at 7, 14 and 21 days after injury. Furthermore, intrathecal administration of MRS2578 (100 μM/day) and NF340 (30 μM/day) for 3 days significantly reduced spinal nerve injury-induced increase in P2Y6,11 receptors expression, respectively. Spinal treatment (on day 14 after injury) with minocycline (100 μg/day) or fluorocitrate (1 nmol/day) for 7 days reduced tactile allodynia and spinal nerve injury-induced up-regulation in Iba-1 and GFAP, respectively. In addition, minocycline reduced nerve injury-induced up-regulation in P2Y6,11 receptors whereas that fluorocitrate diminished P2Y11, but not P2Y6, receptors up-regulation. Intrathecal treatment (on day 21 after injury) with the selective P2Y6 (PSB0474, 3-30 μM) and P2Y11 (NF546, 1-10 μM) receptor agonists produced remarkable tactile allodynia in nerve ligated rats previously treated with minocycline or fluorocitrate for 7 days. Our data suggest that spinal P2Y6 is present in spinal microglia while P2Y11 receptors are present in both spinal microglia and astrocytes, and both receptors are up-regulated in rats subjected to spinal nerve injury. In addition, our data suggest that the spinal P2Y6 and P2Y11

  9. P2X7R: a potential key regulator of acute gouty arthritis.

    Science.gov (United States)

    Tao, Jin-Hui; Zhang, Yong; Li, Xiang-Pei

    2013-12-01

    Acute gouty arthritis is an inflammatory disease resulting from the precipitation of long-term hyperuricemia-induced monosodium urate (MSU) crystals in joints, which stimulates the production of interleukin-1beta (IL-1β) and initiates an inflammatory reaction. However, some patients having MSU crystals in the joints never develop acute gouty arthritis, indicating that other predisposing factors are required for the disease onset. This review described the mechanism of production of IL-1β by MSU crystals and other possible factors during a gout attack. The relevant English literature on IL-1β secretion stimulated by MSU crystals and other possible factors during acute gouty arthritis flares was searched and carefully reviewed. MSU crystals lead to the onset of acute gouty arthritis mainly through the activation of Toll-like receptors (TLRs) and NACHT-LRR-PYD-containing protein 3 (NALP3) inflammasome signaling and downstream IL-1β production. The predisposing factors of acute gouty arthritis, such as strenuous exercise, cold, alcolholism, and overeating have a common characteristic inducing dramatic changes of adenosine triphosphate (ATP) in the body. The ATP changes can activate the purinergic receptor P2X ligand-gated ion channel 7 (P2X7R) signaling system to regulate IL-1β secretion. We hypothesize that acute gouty arthritis is induced by two synergistic effects; one is the stimulation of MSU crystals and the other is the activation of P2X7R signaling pathways by extracellular ATP changes, which together lead to the production of IL-1β and the initiation of acute gouty arthritis. This hypothesis will provide a new avenue for the prevention and treatment of acute gouty arthritis. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Physiopathological implications of P2X1 and P2X7 receptors in regulation of glomerular hemodynamics in angiotensin II-induced hypertension.

    Science.gov (United States)

    Franco, Martha; Bautista-Pérez, Rocío; Cano-Martínez, Agustina; Pacheco, Ursino; Santamaría, José; Del Valle Mondragón, Leonardo; Pérez-Méndez, Oscar; Navar, L Gabriel

    2017-07-01

    Deleterious effects of purinergic P2X 1 and P2X 7 receptors (P2XRs) in ANG II-dependent hypertension include increased renal vascular resistance, and impaired autoregulation and pressure natriuresis. However, their specific effects on the determinants of glomerular hemodynamics remain incompletely delineated. To investigate the P2XR contributions to altered glomerular hemodynamics in hypertension, the effects of acute blockade of P2X 1 R, P2X 7 R, and P2X 4 R with NF449, A438079, and PSB12054, respectively, were evaluated in ANG II-infused rats (435 ng·kg -1 ·min -1 ). P2X 1 R or P2X 7 R blockade reduced afferent (6.85 ± 1.05 vs. 2.37 ± 0.20 dyn·s -1 ·cm -5 ) and efferent (2.85 ± 0.38 vs. 0.99 ± 0.07 dyn·s -1 ·cm -5 ) arteriolar resistances, leading to increases in glomerular plasma flow (75.82 ± 5.58 vs. 206.7 ± 16.38 nl/min), ultrafiltration coefficient (0.0198 ± 0.0024 vs. 0.0512 ± 0.0046 nl·min -1 ·mmHg -1 ), and single-nephron glomerular filtration rate (22.73 ± 2.02 vs. 51.56 ± 3.87 nl/min) to near normal values. Blockade of P2X 4 R did not elicit effects in hypertensive rats. In normotensive sham-operated rats, only the P2X 1 R antagonist caused an increase plasma flow and single-nephron glomerular filtration rate, whereas the P2X 4 R antagonist induced glomerular vasoconstriction that was consistent with evidence that P2X 4 R stimulation increases release of nitric oxide from endothelial cells. Mean arterial pressure remained unchanged in both hypertensive and normotensive groups. Western blot analysis showed overexpression of P2X 1 R, P2X 7 R, and P2X 4 R proteins in hypertensive rats. Whereas it has been generally assumed that the altered glomerular vascular resistances in ANG II hypertension are due to AT 1 receptor-mediated vasoconstriction, these data indicate a predominant P2X 1 R and P2X 7 R control of glomerular hemodynamics in ANG II hypertension. Copyright © 2017 the American Physiological Society.

  11. Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.

    Science.gov (United States)

    Kimbler, Donald E; Shields, Jessica; Yanasak, Nathan; Vender, John R; Dhandapani, Krishnan M

    2012-01-01

    Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7-/- mice) of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1β (IL-1β) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG), a clinically non-toxic P2X7 inhibitor, inhibited IL-1β expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.

  12. Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.

    Directory of Open Access Journals (Sweden)

    Donald E Kimbler

    Full Text Available Traumatic brain injury (TBI is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7-/- mice of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1β (IL-1β and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG, a clinically non-toxic P2X7 inhibitor, inhibited IL-1β expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP, a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4, an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.

  13. Evaluation of TVA`s model site and individual technology pollution prevention demonstration programs and their impact on the agrichemical industry

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, G.S.

    1995-06-01

    The high volume of fertilizer and pesticides funneled through a relatively small number of distribution outlets has made these agribusiness sites potential sources of surface/groundwater contamination in watersheds surrounding the agrichemical facilities. The agrichemical industry came under increased pressures in the mid-1980s to implement environmentally sound management practices and to install containment structures around fertilizer and chemical storage/handling areas to prevent future contamination of existing sites or the movement of contaminants offsite. TVA`s long and successful history of technology transfer to the retail fertilizer industry, as well as the technical expertise of the Agency`s staff, made TVA ideally suited to handle the new environmental challenge. It was during this time period that TVA`s Model Site Demonstration Program (MSD) and Individual Technology Demonstration Program (ITD) were conceived. Since inception, the pollution prevention program and the technologies advanced by it have made a very positive impact on the US agrichemical industry, as well as on other TVA programs. This paper is an attempt to document these impacts, with primary focus being placed on the program`s impact on the agribusiness dealer who implements the pollution prevention technologies/practices recommended by TVA.

  14. A 2-layer and P2P-based architecture on resource location in future grid environment

    International Nuclear Information System (INIS)

    Pei Erming; Sun Gongxin; Zhang Weiyi; Pang Yangguang; Gu Ming; Ma Nan

    2004-01-01

    Grid and Peer-to-Peer computing are two distributed resource sharing environments developing rapidly in recent years. The final objective of Grid, as well as that of P2P technology, is to pool large sets of resources effectively to be used in a more convenient, fast and transparent way. We can speculate that, though many difference exists, Grid and P2P environments will converge into a large scale resource sharing environment that combines the characteristics of the two environments: large diversity, high heterogeneity (of resources), dynamism, and lack of central control. Resource discovery in this future Grid environment is a basic however, important problem. In this article. We propose a two-layer and P2P-based architecture for resource discovery and design a detailed algorithm for resource request propagation in the computing environment discussed above. (authors)

  15. Technology.

    Science.gov (United States)

    Online-Offline, 1998

    1998-01-01

    Focuses on technology, on advances in such areas as aeronautics, electronics, physics, the space sciences, as well as computers and the attendant progress in medicine, robotics, and artificial intelligence. Describes educational resources for elementary and middle school students, including Web sites, CD-ROMs and software, videotapes, books,…

  16. Design and Implementation of an Automated Management Platform for P2P Transactions with Electronic Money

    Directory of Open Access Journals (Sweden)

    Andrés Alcocer

    2016-03-01

    Full Text Available Electronic money is a payment tool implemented by the Ecuador’s Central Bank, it allows people to make commercial transactions using their cellphones; it can be used to pay into big chain stores like supermarkets, known as "macro agents", but it also can be employed for the consumption of goods and services into particular businesses such as restaurants or small shops by using “person to person” transfers known as P2P. However, the particular businesses present some disadvantages compared to the macro agents, the main one is the lack of a system that allows them to have a record of the transactions made with electronic money. This article details the design and implementation of a technological platform that allows all types of businesses and people to keep records of their P2P transactions into an automated system with the ability of generating payment’s balance sheets which can be easily viewed through Internet. A research was conducted in order to look for the most efficient technical solution to optimize the available resources. The use of this platform as an external tool extends the capabilities currently provided by the electronic money system.

  17. Knowledge Management Implementation in P2STPIBN as Internal TSO of BAPETEN

    International Nuclear Information System (INIS)

    Nugroho, D.H.

    2016-01-01

    Full text: Awareness of the importance of knowledge management implementation is growing since the launching in 2014 of BAPETEN’s (Nuclear Energy Regulatory Agency of Indonesia) vision to become a world-class nuclear energy regulatory agency. BAPETEN’s prime challenge arises since most of its human resources are still lacking experience, and many senior professionals have retired or are approaching retirement age. These challenges made P2STPIBN (Center for Regulatory Assessment on the Science and Technology of Nuclear Installation and Material) as an internal technical support organization (TSO) in BAPETEN aware that knowledge management should be implemented in advance. Following the BAPETEN Knowledge Management Guideline which was launched at the end of 2015, P2STPIBN, as part of BAPETEN, activated the knowledge management programme by creating a roadmap and programmes, such as a knowledge map and taxonomy, and a portal for knowledge repository (in progress). In the first quarter of FY of 2016 we started to build CoPs (community of practices) for the Nuclear Reactor Analysis, Nuclear Cyber Security and Nuclear Safety Culture based-on consideration of the needs on the most urgent knowledge. The CoP programme has run from the 2nd week of March 2016. The estimated challenges and anticipations are also discussed. (author

  18. Evolutionary Game Theory-Based Evaluation of P2P File-Sharing Systems in Heterogeneous Environments

    Directory of Open Access Journals (Sweden)

    Yusuke Matsuda

    2010-01-01

    Full Text Available Peer-to-Peer (P2P file sharing is one of key technologies for achieving attractive P2P multimedia social networking. In P2P file-sharing systems, file availability is improved by cooperative users who cache and share files. Note that file caching carries costs such as storage consumption and processing load. In addition, users have different degrees of cooperativity in file caching and they are in different surrounding environments arising from the topological structure of P2P networks. With evolutionary game theory, this paper evaluates the performance of P2P file sharing systems in such heterogeneous environments. Using micro-macro dynamics, we analyze the impact of the heterogeneity of user selfishness on the file availability and system stability. Further, through simulation experiments with agent-based dynamics, we reveal how other aspects, for example, synchronization among nodes and topological structure, affect the system performance. Both analytical and simulation results show that the environmental heterogeneity contributes to the file availability and system stability.

  19. Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists.

    Science.gov (United States)

    Ko, Hyojin; Carter, Rhonda L; Cosyn, Liesbet; Petrelli, Riccardo; de Castro, Sonia; Besada, Pedro; Zhou, Yixing; Cappellacci, Loredana; Franchetti, Palmarisa; Grifantini, Mario; Van Calenbergh, Serge; Harden, T Kendall; Jacobson, Kenneth A

    2008-06-15

    The phosphate, uracil, and ribose moieties of uracil nucleotides were varied structurally for evaluation of agonist activity at the human P2Y(2), P2Y(4), and P2Y(6) receptors. The 2-thio modification, found previously to enhance P2Y(2) receptor potency, could be combined with other favorable modifications to produce novel molecules that exhibit high potencies and receptor selectivities. Phosphonomethylene bridges introduced for stability in analogues of UDP, UTP, and uracil dinucleotides markedly reduced potency. Truncation of dinucleotide agonists of the P2Y(2) receptor, in the form of Up(4)-sugars, indicated that a terminal uracil ring is not essential for moderate potency at this receptor and that specific SAR patterns are observed at this distal end of the molecule. Key compounds reported in this study include 9, alpha,beta-methylene-UDP, a P2Y(6) receptor agonist; 30, Up(4)-phenyl ester and 34, Up(4)-[1]glucose, selective P2Y(2) receptor agonists; dihalomethylene phosphonate analogues 16 and 41, selective P2Y(2) receptor agonists; 43, the 2-thio analogue of INS37217 (P(1)-(uridine-5')-P(4)-(2'-deoxycytidine-5')tetraphosphate), a potent and selective P2Y(2) receptor agonist.

  20. Dabigatran for the prevention of stroke and systemic embolism in atrial fibrillation: A NICE single technology appraisal.

    Science.gov (United States)

    Faria, Rita; Spackman, Eldon; Burch, Jane; Corbacho, Belen; Todd, Derick; Pepper, Chris; Woolacott, Nerys; Palmer, Stephen

    2013-07-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of dabigatran etexilate (Boehringer Ingelheim Ltd, UK) to submit evidence for the clinical and cost-effectiveness of this drug for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) as part of the NICE single technology appraisal process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the evidence review group (ERG). This article presents a summary of the manufacturer's submission, the ERG report and the subsequent development of NICE guidance for the use of dabigatran within the UK National Health Service. Dabigatran was granted marketing authorisation by the European Medicines Agency for a sequential dosing regimen (DBG sequential), in which patients under 80 years are treated with dabigatran 150 mg twice daily (DBG150) and patients 80 years and over are given dabigatran 110 mg twice daily (DBG110). NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the committee was whether the DBG sequential regimen was effective and cost-effective compared with warfarin or aspirin for patients with non-valvular AF and one or more risk factors. The RE-LY trial, a large multi-centre non-inferiority randomised clinical trial, was the primary source of clinical evidence. DBG150 was shown to be non-inferior, and subsequently superior to warfarin, for the primary outcome of all stroke/systemic embolism. DBG110 was found to be non-inferior to warfarin. Results were presented for a post hoc subgroup analysis for patients under and over 80 years of age, where DBG110 showed a statistically significant reduction of haemorrhagic stroke and intracranial haemorrhage in comparison to warfarin in patients over 80 years of age. This post hoc subgroup analysis by age was the basis for the licensed DBG sequential regimen

  1. The role of research methodology in the rational use of technology in monitoring and preventing communication disorders

    Directory of Open Access Journals (Sweden)

    Brasília M. Chiari

    2009-09-01

    Full Text Available Studies showing stronger scientific evidence related to speech, language and hearing pathology (SLP have an impact on the prevention and rehabilitation of human communication and gained ground in SLP research agenda. In this paper we discuss some aspects and directions that should be considered for in-depth knowledge about speech, language and hearing needs in different population groups (age group, gender and other variables according to specific related disorders for improved comprehensive care, successful efforts and effective use of financial and human resources. It is also discussed the decision making process for requesting complementary evaluations and tests, from routine to highly complex ones, that should be based on each test and/or procedure and their contribution to the diagnosis and therapeutic planning. In fact, it is crucial to have reliable parameters for planning, preventing and treating human communication and its related disorders. Epidemiology, biostatistics and social sciences can contribute with more specific information in human communication sciences and guide more specific studies on the international science and technology agenda, improving communication sciences involvement in the international health-related scientific scenario.Estudos que demonstram mais evidências científicas associadas ao impacto da Fonoaudiologia na prevenção e reabilitação da comunicação humana vêm ganhando maior espaço na agenda fonoaudiológica. Neste artigo discutimos alguns aspectos relacionados a essa questão, bem como direcionamentos a se-rem considerados para que conhecimento mais detalhado relacionado à Fonoaudiologia em estratos diferentes da população (como faixa etária, sexo, etc. associadas a estes agravos esteja disponível, a fim de contribuir com a integralidade e efetividade dos recursos humanos e financeiros na atenção à saúde. Além disso, discutimos aspectos inerentes à solicitação de avaliações e exames

  2. Tools and drugs for uracil nucleotide-activated P2Y receptors.

    Science.gov (United States)

    Rafehi, Muhammad; Müller, Christa E

    2018-04-13

    P2Y receptors (P2YRs) are a family of G protein-coupled receptors activated by extracellular nucleotides. Physiological P2YR agonists include purine and pyrimidine nucleoside di- and triphosphates, such as ATP, ADP, UTP, UDP, nucleotide sugars, and dinucleotides. Eight subtypes exist, P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , P2Y 11 , P2Y 12 , P2Y 13 , and P2Y 14 , which represent current or potential future drug targets. Here we provide a comprehensive overview of ligands for the subgroup of the P2YR family that is activated by uracil nucleotides: P2Y 2 (UTP, also ATP and dinucleotides), P2Y 4 (UTP), P2Y 6 (UDP), and P2Y 14 (UDP, UDP-glucose, UDP-galactose). The physiological agonists are metabolically unstable due to their fast hydrolysis by ectonucleotidases. A number of agonists with increased potency, subtype-selectivity and/or enzymatic stability have been developed in recent years. Useful P2Y 2 R agonists include MRS2698 (6-01, highly selective) and PSB-1114 (6-05, increased metabolic stability). A potent and selective P2Y 2 R antagonist is AR-C118925 (10-01). For studies of the P2Y 4 R, MRS4062 (3-15) may be used as a selective agonist, while PSB-16133 (10-06) represents a selective antagonist. Several potent P2Y 6 R agonists have been developed including 5-methoxyuridine 5'-O-((R p )α-boranodiphosphate) (6-12), PSB-0474 (3-11), and MRS2693 (3-26). The isocyanate MRS2578 (10-08) is used as a selective P2Y 6 R antagonist, although its reactivity and low water-solubility are limiting. With MRS2905 (6-08), a potent and metabolically stable P2Y 14 R agonist is available, while PPTN (10-14) represents a potent and selective P2Y 14 R antagonist. The radioligand [ 3 H]UDP can be used to label P2Y 14 Rs. In addition, several fluorescent probes have been developed. Uracil nucleotide-activated P2YRs show great potential as drug targets, especially in inflammation, cancer, cardiovascular and neurodegenerative diseases. Copyright © 2018. Published by Elsevier Inc.

  3. A review on prevention and treatment of post-orthodontic white spot lesions - evidence-based methods and emerging technologies

    DEFF Research Database (Denmark)

    Bergstrand, Fredrik; Twetman, Svante

    2011-01-01

    The aim of this paper was to update the evidence for primary and secondary prevention (treatment) of white spot lesions (WSL) adjacent to fixed orthodontic appliances.......The aim of this paper was to update the evidence for primary and secondary prevention (treatment) of white spot lesions (WSL) adjacent to fixed orthodontic appliances....

  4. AN EXAMINATION OF THE ADVANCES IN SCIENCE AND TECHNOLOGY OF PREVENTION OF TOOTH DECAY IN YOUNG CHILDREN SINCE THE SURGEON GENERAL’S REPORT ON ORAL HEALTH

    Science.gov (United States)

    Milgrom, Peter; Zero, Domenick T.; Tanzer, Jason M.

    2009-01-01

    This paper addresses a number of areas related to how effectively science and technology have met Healthy People 2010 goals for tooth decay prevention. In every area mentioned, it appears that science and technology are falling short of these goals. Earlier assessments identified water fluoridation as one of the greatest public health accomplishments of the last century. Yet, failure to complete needed clinical and translational research has shortchanged the caries prevention agenda that incomplete at a critical juncture. Science has firmly established the transmissible nature of tooth decay. However, there is evidence that tooth decay in young children is increasing although progress has been made in other age groups. Studies of risk assessment have not been translated into improved practice. Antiseptics, chlorhexidine varnish, and PVP-iodine may have value, but definitive trials are needed. Fluorides remain the most effective agents, but are not widely disseminated to the most needy. Fluoride varnish provides a relatively effective topical preventive for very young children, yet definitive trials have not been conducted. Silver diammine fluoride also has potential but requires study in the US. Data support effectiveness and safety of xylitol, but adoption is not widespread. Dental sealants remain a mainstay of public policy, yet after decades of research, widespread use has not occurred. We conclude that research has established the public health burden of tooth decay, but insufficient research addresses the problems identified in the Surgeon General's Report. Transfer of technology from studies to implementation is needed to prevent tooth decay among children. This should involve translational research and implementation of scientific and technological advances into practice. PMID:19837019

  5. An examination of the advances in science and technology of prevention of tooth decay in young children since the Surgeon General's Report on Oral Health.

    Science.gov (United States)

    Milgrom, Peter; Zero, Domenick T; Tanzer, Jason M

    2009-01-01

    This paper addresses a number of areas related to how effectively science and technology have met Healthy People 2010 goals for tooth decay prevention. In every area mentioned, it appears that science and technology are falling short of these goals. Earlier assessments identified water fluoridation as one of the greatest public health accomplishments of the last century. Yet, failure to complete needed clinical and translational research has shortchanged the caries prevention agenda at a critical juncture. Science has firmly established the transmissible nature of tooth decay. However, there is evidence that tooth decay in young children is increasing, although progress has been made in other age groups. Studies of risk assessment have not been translated into improved practice. Antiseptics, chlorhexidine varnish, and polyvinylpyrrolidone iodine (PVI-I) may have value, but definitive trials are needed. Fluorides remain the most effective agents, but are not widely disseminated to the most needy. Fluoride varnish provides a relatively effective topical preventive for very young children, yet definitive trials have not been conducted. Silver diamine fluoride also has potential but requires study in the United States. Data support effectiveness and safety of xylitol, but adoption is not widespread. Dental sealants remain a mainstay of public policy, yet after decades of research, widespread use has not occurred. We conclude that research has established the public health burden of tooth decay, but insufficient research addresses the problems identified in the report Oral Health in America: A Report of the Surgeon General. Transfer of technology from studies to implementation is needed to prevent tooth decay among children. This should involve translational research and implementation of scientific and technological advances into practice.

  6. Ion channel regulation by phosphoinositides analyzed with VSPs—PI(4,5)P2 affinity, phosphoinositide selectivity, and PI(4,5)P2 pool accessibility

    Science.gov (United States)

    Rjasanow, Alexandra; Leitner, Michael G.; Thallmair, Veronika; Halaszovich, Christian R.; Oliver, Dominik

    2015-01-01

    The activity of many proteins depends on the phosphoinositide (PI) content of the membrane. E.g., dynamic changes of the concentration of PI(4,5)P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5)P2. Yet, measuring affinities for endogenous PIs has not been possible directly, but has relied largely on the response to soluble analogs, which may not quantitatively reflect binding to native lipids. Voltage-sensitive phosphatases (VSPs) turn over PI(4,5)P2 to PI(4)P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5)P2. Because cellular PI(4,5)P2 is resynthesized rapidly, steady state PI(4,5)P2 changes with the degree of VSP activation and thus depends on membrane potential. Here we show that titration of endogenous PI(4,5)P2 with Ci-VSP allows for the quantification of relative PI(4,5)P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K+ channels to Ci-VSP allowed for comparison of PI(4,5)P2 affinities within and across channel subfamilies and detected changes of affinity in mutant channels. The results also reveal that VSPs are useful only for PI effectors with high binding specificity among PI isoforms, because PI(4,5)P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5)P2 and PI(4)P was insensitive to VSP. Surprisingly, despite comparable PI(4,5)P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor-mediated depletion of PI(4,5)P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5)P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5)P2 that differ in their accessibility to PLC and VSPs. PMID

  7. Ion channel regulation by phosphoinositides analyzed with VSPs – PI(4,5P2 affinity, phosphoinositide selectivity, and PI(4,5P2 pool accessibility

    Directory of Open Access Journals (Sweden)

    Alexandra eRjasanow

    2015-06-01

    Full Text Available The activity of many proteins depends on the phosphoinositide (PI content of the membrane. E.g., dynamic changes of the concentration of PI(4,5P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5P2. Yet, measuring affinities for endogenous PIs has not been possible directly, but has relied largely on the response to soluble analogs, which may not quantitatively reflect binding to native lipids.Voltage-sensitive phosphatases (VSPs turn over PI(4,5P2 to PI(4P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5P2. Because cellular PI(4,5P2 is resynthesized rapidly, steady state PI(4,5P2 changes with the degree of VSP activation and thus depends on membrane potential.Here we show that titration of endogenous PI(4,5P2 with Ci-VSP allows for the quantification of relative PI(4,5P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K+ channels to Ci-VSP allowed for comparison of PI(4,5P2 affinities within and across channel subfamilies and detected changes of affinity in mutant channels. The results also reveal that VSPs are useful only for PI effectors with high binding specificity among PI isoforms, because PI(4,5P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5P2 and PI(4P was insensitive to VSP.Surprisingly, despite comparable PI(4,5P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor-mediated depletion of PI(4,5P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5P2 that differ in their accessibility to PLC and VSPs.

  8. Circadian ATP Release in Organotypic Cultures of the Rat Suprachiasmatic Nucleus Is Dependent on P2X7 and P2Y Receptors

    Directory of Open Access Journals (Sweden)

    Irena Svobodova

    2018-03-01

    Full Text Available The circadian rhythms in physiological and behavioral functions are driven by a pacemaker located in the suprachiasmatic nucleus (SCN. The rhythms continue in constant darkness and depend on cell-cell communication between neurons and glia. The SCN astrocytes generate also a circadian rhythm in extracellular adenosine 5′-triphosphate (ATP accumulation, but molecular mechanisms that regulate ATP release are poorly understood. Here, we tested the hypothesis that ATP is released via the plasma membrane purinergic P2X7 receptors (P2X7Rs and P2Y receptors (P2YRs which have been previously shown to be expressed in the SCN tissue at transcriptional level. We have investigated this hypothesis using SCN organotypic cultures, primary cultures of SCN astrocytes, ATP bioluminescent assays, immunohistochemistry, patch-clamping, and calcium imaging. We found that extracellular ATP accumulation in organotypic cultures followed a circadian rhythm, with a peak between 24:00 and 04:00 h, and the trough at ~12:00 h. ATP rhythm was inhibited by application of AZ10606120, A438079, and BBG, specific blockers of P2X7R, and potentiated by GW791343, a positive allosteric modulator of this receptor. Double-immunohistochemical staining revealed high expression of the P2X7R protein in astrocytes of SCN slices. PPADS, a non-specific P2 antagonist, and MRS2179, specific P2Y1R antagonist, also abolished ATP rhythm, whereas the specific P2X4R blocker 5-BDBD was not effective. The pannexin-1 hemichannel blocker carbenoxolone displayed a partial inhibitory effect. The P2Y1R agonist MRS2365, and the P2Y2R agonist MRS2768 potentiated ATP release in organotypic cultures and increase intracellular Ca2+ level in cultured astrocytes. Thus, SCN utilizes multiple purinergic receptor systems and pannexin-1 hemichannels to release ATP.

  9. Technology

    Directory of Open Access Journals (Sweden)

    Xu Jing

    2016-01-01

    Full Text Available The traditional answer card reading method using OMR (Optical Mark Reader, most commonly, OMR special card special use, less versatile, high cost, aiming at the existing problems proposed a method based on pattern recognition of the answer card identification method. Using the method based on Line Segment Detector to detect the tilt of the image, the existence of tilt image rotation correction, and eventually achieve positioning and detection of answers to the answer sheet .Pattern recognition technology for automatic reading, high accuracy, detect faster

  10. Purinergic receptors P2Y12R and P2X7R: potential targets for PET imaging of microglia phenotypes in multiple sclerosis.

    Science.gov (United States)

    Beaino, Wissam; Janssen, Bieneke; Kooij, Gijs; van der Pol, Susanne M A; van Het Hof, B; van Horssen, Jack; Windhorst, Albert D; de Vries, Helga E

    2017-12-22

    Microglia are major players in the pathogenesis of multiple sclerosis (MS) and may play a dual role in disease progression. The activation status of microglia in vivo is highly dynamic and occurs as a continuum, with the pro-inflammatory and anti-inflammatory phenotypes on either end of this spectrum. Little is known about in vivo dynamics of microglia phenotypes in MS due to the lack of diagnostic tools. Positron emission tomography (PET) imaging is a powerful non-invasive technique that allows real-time imaging of microglia activation phenotypes in the central nervous system, depending on the availability of selective PET tracers. Our objective is to investigate and characterize the expression of the purinergic receptors P2Y12R and P2X7R as potential targets for PET tracer development and subsequent PET imaging in order to evaluate the dynamics of microglia status in vivo. We used immunohistochemical analysis to explore the expression of P2Y12R and P2X7R in experimental autoimmune encephalomyelitis (EAE) post-mortem tissues and different stages of well-characterized MS lesions. We evaluated by quantitative real-time polymerase chain reaction the expression of P2Y12R and P2X7R in human polarized microglia, and we performed autoradiography binding assay with radiolabeled P2Y12R and P2X7R antagonists using MS and rat EAE tissues. Here, we demonstrate that P2X7R is associated with a pro-inflammatory phenotype of human microglia in vitro, and is highly expressed in microglia in MS lesions as well as during the peak of EAE. In contrast, P2Y12R was associated with an anti-inflammatory phenotype in human microglia in vitro and was expressed at lower levels in active inflammatory MS lesions compared to normal-appearing white matter (NAWM) and similarly in EAE, while its expression increased in the remission phase of EAE. Binding of radiolabeled tracers specific for P2Y12R and P2X7R on ex vivo tissues validated the value of these receptors as PET imaging targets for

  11. Influence of After-Growth Treatments on the Optical Parameters of Teraherz ZnGeP2 Crystals

    Science.gov (United States)

    Gribenyukov, A. I.; Dorozhkin, K. V.; Morozov, A. N.; Suslyaev, V. I.

    2018-03-01

    Results of investigations are presented of the THz spectra of the refractive index n(v) and of the extinction coefficient k(v) for ZnGeP2 single crystals with different degrees of technological treatment - after growth by the vertical Bridgman technique, after heat treatment at temperatures above the Debye temperature for the highest-frequency phonons, and after modification of the single-crystal properties under irradiation by fast electrons ( 4 MeV).

  12. Hypoxia attenuates purinergic P2X receptor-induced inflammatory gene expression in brainstem microglia

    Directory of Open Access Journals (Sweden)

    Smith SMC

    2013-08-01

    Full Text Available Stephanie MC Smith,1,2 Gordon S Mitchell,1,2 Scott A Friedle,3 Christine M Sibigtroth,1 Stéphane Vinit,1 Jyoti J Watters1–31Department of Comparative Biosciences, 2Comparative Biomedical Sciences Training Program, 3Program in Cellular and Molecular Biology, University of Wisconsin, Madison, WI, USAAbstract: Hypoxia and increased extracellular nucleotides are frequently coincident in the brainstem. Extracellular nucleotides are potent modulators of microglial inflammatory gene expression via P2X purinergic receptor activation. Although hypoxia is also known to modulate inflammatory gene expression, little is known about how hypoxia or P2X receptor activation alone affects inflammatory molecule production in brainstem microglia, nor how hypoxia and P2X receptor signaling interact when they occur together. In the study reported here, we investigated the ability of a brief episode of hypoxia (2 hours in the presence and absence of the nonselective P2X receptor agonist 2′(3′-O-(4-benzoylbenzoyladenosine-5′-triphosphate (BzATP to promote inflammatory gene expression in brainstem microglia in adult rats. We evaluated inducible nitric oxide synthase (iNOS, tumor necrosis factor alpha (TNFα, and interleukin (IL-6 messenger RNA levels in immunomagnetically isolated brainstem microglia. While iNOS and IL-6 gene expression increased with hypoxia and BzATP alone, TNFα expression was unaffected. Surprisingly, BzATP-induced inflammatory effects were lost after hypoxia, suggesting that hypoxia impairs proinflammatory P2X-receptor signaling. We also evaluated the expression of key P2X receptors activated by BzATP, namely P2X1, P2X4, and P2X7. While hypoxia did not alter their expression, BzATP upregulated P2X4 and P2X7 mRNAs; these effects were ablated in hypoxia. Although both P2X4 and P2X7 receptor expression correlated with increased microglial iNOS and IL-6 levels in microglia from normoxic rats, in hypoxia, P2X7 only correlated with IL-6, and P2X

  13. Peristalsis is impaired in the small intestine of mice lacking the P2X3 subunit.

    Science.gov (United States)

    Bian, Xiaochun; Ren, Jianhua; DeVries, Matthew; Schnegelsberg, Birthe; Cockayne, Debra A; Ford, Anthony P D W; Galligan, James J

    2003-08-15

    P2X receptors are ATP-gated cation channels composed of one or more of seven different subunits. P2X receptors participate in intestinal neurotransmission but the subunit composition of enteric P2X receptors is unknown. In this study, we used tissues from P2X3 wild-type (P2X3+/+) mice and mice in which the P2X3 subunit gene had been deleted (P2X3-/-) to investigate the role of this subunit in neurotransmission in the intestine. RT-PCR analysis of mRNA from intestinal tissues verified P2X3 gene deletion. Intracellular electrophysiological methods were used to record synaptic and drug-induced responses from myenteric neurons in vitro. Drug-induced longitudinal muscle contractions were studied in vitro. Intraluminal pressure-induced reflex contractions (peristalsis) of ileal segments were studied in vitro using a modified Trendelenburg preparation. Gastrointestinal transit was measured as the progression in 30 min of a liquid radioactive marker administered by gavage to fasted mice. Fast excitatory postsynaptic potentials recorded from S neurons (motoneurons and interneurons) were similar in tissues from P2X3+/+ and P2X3-/- mice. S neurons from P2X3+/+ and P2X3-/- mice were depolarized by application of ATP but not alpha,beta-methylene ATP, an agonist of P2X3 subunit-containing receptors. ATP and alpha,beta-methylene ATP induced depolarization of AH (sensory) neurons from P2X3+/+ mice. ATP, but not alpha,beta-methylene ATP, caused depolarization of AH neurons from P2X3-/- mice. Peristalsis was inhibited in ileal segments from P2X3-/- mice but longitudinal muscle contractions caused by nicotine and bethanechol were similar in segments from P2X3+/+ and P2X3-/- mice. Gastrointestinal transit was similar in P2X3+/+ and P2X3-/- mice. It is concluded that P2X3 subunit-containing receptors participate in neural pathways underlying peristalsis in the mouse intestine in vitro. P2X3 subunits are localized to AH (sensory) but not S neurons. P2X3 receptors may contribute to

  14. Band offset at the heterojunction interfaces of CdS/ZnSnP2, ZnS/ZnSnP2, and In2S3/ZnSnP2

    Science.gov (United States)

    Nakatsuka, Shigeru; Nose, Yoshitaro; Shirai, Yasuharu

    2016-05-01

    Heterojunctions were formed between ZnSnP2 and buffer materials, CdS, ZnS, and In2S3, using chemical bath deposition. The band offset was investigated by X-ray photoelectron spectroscopy based on Kraut method. The conduction band offset, ΔEC, between ZnSnP2 and CdS was estimated to be -1.2 eV, which significantly limits the open circuit voltage, VOC. Conversely, ΔEC at the heterojunction between ZnSnP2 and ZnS was +0.3 eV, which is within the optimal offset range. In the case of In2S3, ΔEC was a relatively small value, -0.2 eV, and In2S3 is potentially useful as a buffer layer in ZnSnP2 solar cells. The J-V characteristics of heterojunction diodes with an Al/sulfides/ZnSnP2 bulk/Mo structure also suggested that ZnS and In2S3 are promising candidates for buffer layers in ZnSnP2 thin film solar cells, and the band alignment is a key factor for the higher efficiency of solar cells with heterojunctions.

  15. Decree No. 89-85 of 8 February 1989 setting up a Council on Technological Risk Prevention

    International Nuclear Information System (INIS)

    1989-01-01

    The Council set up by this Decree contributes to the assessment of collective risks arising from industrial activities, in particular nuclear activities, through its opinions, recommendations, studies, and proposes the relevant preventive actions to the Government. (NEA) [fr

  16. Evidence-Based Integrated Environmental Solutions For Secondary Lead Smelters: Pollution Prevention And Waste Minimization Technologies And Practices

    Science.gov (United States)

    An evidence-based methodology was adopted in this research to establish strategies to increase lead recovery and recycling via a systematic review and critical appraisal of the published literature. In particular, the research examines pollution prevention and waste minimization...

  17. Cyber Security at the District Level: Are You Ready to Prevent Unlawful, Unauthorized or Simply Misguided Use of Your Technology?

    Science.gov (United States)

    Lafee, Scott

    2005-01-01

    In an era of digital technologies, school districts find themselves on a cutting edge, one that slices both ways. Technological tools like the Internet, e-mail, networked computers and such have revolutionized the way children are taught and schools are run, but they also have created new management challenges and ethical issues that many school…

  18. Endothelial P2X7 receptors’ expression is reduced by schistosomiasis

    OpenAIRE

    Oliveira, Suellen D’Arc dos Santos; Coutinho-Silva, Robson; Silva, Claudia Lucia Martins

    2012-01-01

    Endothelial cells control vascular tone, permeability and leukocyte transmigration and are modulated by pro-inflammatory mediators. Schistosomiasis is an intravascular disease associated with inflammation, therefore altering endothelial cells’ phenotype. Purinergic P2X7 receptors (P2X7R) play an important role in inflammation; however, the impact of the disease upon endothelial P2X7R function or expression has not been explored. Using ethidium bromide uptake to investigate P2X7R function, we ...

  19. P2P Evolution: from file-sharing to decentralized workflows

    NARCIS (Netherlands)

    Risse, Thomas; Knezevic, Predrag; Wombacher, Andreas

    Peer-to-peer (P2P) computing is currently receiving a great deal of attention. Much of the current attention is focused on the use of P2P computing for exchanging media files. But P2P systems have actually been around for a long time and many application scenarios exist. In this paper we discuss on

  20. Music2Share - Copyright-Compliant Music Sharing in P2P Systems

    NARCIS (Netherlands)

    Kalker, Ton; Epema, Dick H.J.; Hartel, Pieter H.; Lagendijk, R. (Inald) L.; van Steen, Martinus Richardus; van Steen, Maarten

    Peer-to-Peer (P2P) networks are generally considered to be free havens for pirated content, in particular with respect to music. We describe a solution for the problem of copyright infringement in P2P networks for music sharing. In particular, we propose a P2P protocol that integrates the functions

  1. Music2Share --- Copyright-Compliant Music Sharing in P2P Systems

    NARCIS (Netherlands)

    Kalker, T.; Epema, D.; Hartel, P.; Lagendijk, I.; van Steen, M.R.

    2004-01-01

    Peer-to-peer (P2P) networks are generally considered to be free havens for pirated content, in particular with respect to music. We describe a solution for the problem of copyright infringement in P2P networks for music sharing. In particular, we propose a P2P protocol that integrates the functions

  2. Ezrin/Radixin/Moesin Are Required for the Purinergic P2X7 Receptor (P2X7R)-dependent Processing of the Amyloid Precursor Protein*

    Science.gov (United States)

    Darmellah, Amaria; Rayah, Amel; Auger, Rodolphe; Cuif, Marie-Hélène; Prigent, Magali; Arpin, Monique; Alcover, Andres; Delarasse, Cécile; Kanellopoulos, Jean M.

    2012-01-01

    The amyloid precursor protein (APP) can be cleaved by α-secretases in neural cells to produce the soluble APP ectodomain (sAPPα), which is neuroprotective. We have shown previously that activation of the purinergic P2X7 receptor (P2X7R) triggers sAPPα shedding from neural cells. Here, we demonstrate that the activation of ezrin, radixin, and moesin (ERM) proteins is required for the P2X7R-dependent proteolytic processing of APP leading to sAPPα release. Indeed, the down-regulation of ERM by siRNA blocked the P2X7R-dependent shedding of sAPPα. We also show that P2X7R stimulation triggered the phosphorylation of ERM. Thus, ezrin translocates to the plasma membrane to interact with P2X7R. Using specific pharmacological inhibitors, we established the order in which several enzymes trigger the P2X7R-dependent release of sAPPα. Thus, a Rho kinase and the MAPK modules ERK1/2 and JNK act upstream of ERM, whereas a PI3K activity is triggered downstream. For the first time, this work identifies ERM as major partners in the regulated non-amyloidogenic processing of APP. PMID:22891241

  3. Ezrin/radixin/moesin are required for the purinergic P2X7 receptor (P2X7R)-dependent processing of the amyloid precursor protein.

    Science.gov (United States)

    Darmellah, Amaria; Rayah, Amel; Auger, Rodolphe; Cuif, Marie-Hélène; Prigent, Magali; Arpin, Monique; Alcover, Andres; Delarasse, Cécile; Kanellopoulos, Jean M

    2012-10-05

    The amyloid precursor protein (APP) can be cleaved by α-secretases in neural cells to produce the soluble APP ectodomain (sAPPα), which is neuroprotective. We have shown previously that activation of the purinergic P2X7 receptor (P2X7R) triggers sAPPα shedding from neural cells. Here, we demonstrate that the activation of ezrin, radixin, and moesin (ERM) proteins is required for the P2X7R-dependent proteolytic processing of APP leading to sAPPα release. Indeed, the down-regulation of ERM by siRNA blocked the P2X7R-dependent shedding of sAPPα. We also show that P2X7R stimulation triggered the phosphorylation of ERM. Thus, ezrin translocates to the plasma membrane to interact with P2X7R. Using specific pharmacological inhibitors, we established the order in which several enzymes trigger the P2X7R-dependent release of sAPPα. Thus, a Rho kinase and the MAPK modules ERK1/2 and JNK act upstream of ERM, whereas a PI3K activity is triggered downstream. For the first time, this work identifies ERM as major partners in the regulated non-amyloidogenic processing of APP.

  4. A survey of simulators for P2P overlay networks with a case study of the P2P tree overlay using an event-driven simulator

    Directory of Open Access Journals (Sweden)

    Shivangi Surati

    2017-04-01

    Full Text Available Implementation of a P2P (Peer-to-Peer overlay network directly on the realistic network environments is not a feasible initiative as scalability is a major challenge for P2P. The implementation of newly created P2P networks must be analyzed, well tested and evaluated through experiments by researchers and organizations. Various simulators have been developed to analyze and simulate P2P protocols before applying to real applications. However, selection of an appropriate simulator suitable for a given application requires a prior comprehensive survey of P2P simulators. The existing literature survey of P2P simulators has limitations viz. (i all P2P related simulators have not been included, (ii all design criteria for comparison and appropriate selection of the simulator may not be considered, (iii appropriate practical application through the simulation has not been presented to enhance the outcome of a survey. To overcome these limitations, we survey existing simulators with classifications, additional design parameters, limitations and comparison using various criteria. In addition, we discuss about common interface concept that creates a generic application to make the implementation of targeted application portable. Not only that, we present a case study of implementation of BATON (BAlanced Tree Overlay Network and BATON* using an event-driven model of PeerSim simulator that helps the developers to simulate the tree overlays efficiently.

  5. Fall Prevention Self-Assessments Via Mobile 3D Visualization Technologies: Community Dwelling Older Adults' Perceptions of Opportunities and Challenges.

    Science.gov (United States)

    Hamm, Julian; Money, Arthur; Atwal, Anita

    2017-06-19

    In the field of occupational therapy, the assistive equipment provision process (AEPP) is a prominent preventive strategy used to promote independent living and to identify and alleviate fall risk factors via the provision of assistive equipment within the home environment. Current practice involves the use of paper-based forms that include 2D measurement guidance diagrams that aim to communicate the precise points and dimensions that must be measured in order to make AEPP assessments. There are, however, issues such as "poor fit" of equipment due to inaccurate measurements taken and recorded, resulting in more than 50% of equipment installed within the home being abandoned by patients. This paper presents a novel 3D measurement aid prototype (3D-MAP) that provides enhanced measurement and assessment guidance to patients via the use of 3D visualization technologies. The purpose of this study was to explore the perceptions of older adults with regard to the barriers and opportunities of using the 3D-MAP application as a tool that enables patient self-delivery of the AEPP. Thirty-three community-dwelling older adults participated in interactive sessions with a bespoke 3D-MAP application utilizing the retrospective think-aloud protocol and semistructured focus group discussions. The system usability scale (SUS) questionnaire was used to evaluate the application's usability. Thematic template analysis was carried out on the SUS item discussions, think-aloud, and semistructured focus group data. The quantitative SUS results revealed that the application may be described as having "marginal-high" and "good" levels of usability, along with strong agreement with items relating to the usability (P=.004) and learnability (Passessment (SA). The application was seen as a useful tool to enhance visualization of measurement guidance and also to promote independent living, ownership of care, and potentially reduce waiting times. Several design and functionality recommendations

  6. Randomized Controlled Trials of Technology-Based HIV/STI and Drug Abuse Preventive Interventions for African American and Hispanic Youth: Systematic Review.

    Science.gov (United States)

    Córdova, David; Mendoza Lua, Frania; Ovadje, Lauretta; Hong, Ethan; Castillo, Berenice; Salas-Wright, Christopher P

    2017-12-13

    HIV/sexually transmitted infections (STIs) and drug abuse remain significant public health concerns in the United States, and African American and Hispanic youth are disproportionately affected. Although technology-based interventions are efficacious in preventing and reducing HIV/STI and licit/illicit drug use behaviors, relatively little is known regarding the state of the science of these interventions among African American and Hispanic youth. The aim of this review is to identify and examine randomized controlled trials (RCTs) of technology-based HIV/STI and/or drug abuse preventive interventions for African American and Hispanic youth. We searched electronic databases (ie, PubMed, Proquest, PsycINFO, Ebscohost, Google Scholar) to identify studies between January 2006 and October 2016. RCTs of technology-based interventions targeting African American and Hispanic youth HIV/STI risk behaviors, including sexual risk, licit and illicit drug use, and HIV/STI testing were included. Our search revealed a total of three studies that used an RCT design and included samples comprised of >50% African American and/or Hispanic youth. The follow-up assessments ranged from two weeks to six months and the number of participants in each trial ranged from 72 to 141. The three interventions were theory-driven, interactive, and tailored. The long-term effects of the interventions were mixed, and outcomes included reductions in sex partners, licit drug use, and condomless anal sex acts. Although technology-based interventions seem promising in the prevention of HIV/STI and drug abuse among African American and Hispanic youth, more research is needed. ©David Córdova, Frania Mendoza Lua, Lauretta Ovadje, Ethan Hong, Berenice Castillo, Christopher P Salas-Wright. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 13.12.2017.

  7. Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis.

    Science.gov (United States)

    Gulbransen, Brian D; Bashashati, Mohammad; Hirota, Simon A; Gui, Xianyong; Roberts, Jane A; MacDonald, Justin A; Muruve, Daniel A; McKay, Derek M; Beck, Paul L; Mawe, Gary M; Thompson, Roger J; Sharkey, Keith A

    2012-03-18

    Inflammatory bowel diseases (IBDs) are chronic relapsing and remitting conditions associated with long-term gut dysfunction resulting from alterations to the enteric nervous system and a loss of enteric neurons. The mechanisms underlying inflammation-induced enteric neuron death are unknown. Here using in vivo models of experimental colitis we report that inflammation causes enteric neuron death by activating a neuronal signaling complex composed of P2X7 receptors (P2X7Rs), pannexin-1 (Panx1) channels, the Asc adaptor protein and caspases. Inhibition of P2X7R, Panx1, Asc or caspase activity prevented inflammation-induced neuron cell death. Preservation of enteric neurons by inhibiting Panx1 in vivo prevented the onset of inflammation-induced colonic motor dysfunction. Panx1 expression was reduced in Crohn's disease but not ulcerative colitis. We conclude that activation of neuronal Panx1 underlies neuron death and the subsequent development of abnormal gut motility in IBD. Targeting Panx1 represents a new neuroprotective strategy to ameliorate the progression of IBD-associated dysmotility.

  8. Trophic activity of human P2X7 receptor isoforms A and B in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Anna Lisa Giuliani

    Full Text Available The P2X7 receptor (P2X7R is attracting increasing attention for its involvement in cancer. Several recent studies have shown a crucial role of P2X7R in tumour cell growth, angiogenesis and invasiveness. In this study, we investigated the role of the two known human P2X7R functional splice variants, the full length P2X7RA and the truncated P2X7RB, in osteosarcoma cell growth. Immunohistochemical analysis of a tissue array of human osteosarcomas showed that forty-four, of a total fifty-four tumours (81.4%, stained positive for both P2X7RA and B, thirty-one (57.4% were positive using an anti-P2X7RA antibody, whereas fifteen of the total number (27.7% expressed only P2X7RB. P2X7RB positive tumours showed increased cell density, at the expense of extracellular matrix. The human osteosarcoma cell line Te85, which lacks endogenous P2X7R expression, was stably transfected with either P2X7RA, P2X7RB, or both. Receptor expression was a powerful stimulus for cell growth, the most efficient growth-promoting isoform being P2X7RB alone. Growth stimulation was matched by increased Ca(2+ mobilization and enhanced NFATc1 activity. Te85 P2X7RA+B cells presented pore formation as well as spontaneous extracellular ATP release. The ATP release was sustained in all clones by P2X7R agonist (BzATP and reduced following P2X7R antagonist (A740003 application. BzATP also increased cell growth and activated NFATc1 levels. On the other hand cyclosporin A (CSA affected both NFATc1 activation and cell growth, definitively linking P2X7R stimulation to NFATc1 and cell proliferation. All transfected clones also showed reduced RANK-L expression, and an overall decreased RANK-L/OPG ratio. Mineralization was increased in Te85 P2X7RA+B cells while it was significantly diminished in Te85 P2X7RB clones, in agreement with immunohistochemical results. In summary, our data show that the majority of human osteosarcomas express P2X7RA and B and suggest that expression of either isoform is

  9. Polymorphism of NaVO2F2: a P2₁/c superstructure with pseudosymmetry of P2₁/m in the subcell.

    Science.gov (United States)

    Yu, Zi-Qun; Wang, Jing-Quan; Huang, Ya-Xi; Botis, Sanda M; Pan, Yuanming; Mi, Jin-Xiao

    2015-06-01

    The ADDSYM routine in the program PLATON [Spek (2015). Acta Cryst. C71, 9-18] has helped researchers to avoid structures of (metal-)organic compounds being reported in an unnecessarily low symmetry space group. However, determination of the correct space group may get more complicated in cases of pseudosymmetric inorganic compounds. One example is NaVO2F2, which was reported [Crosnier-Lopez et al. (1994). Eur. J. Solid State Inorg. Chem. 31, 957-965] in the acentric space group P2₁ based on properties but flagged by ADDSYM as (pseudo)centrosymmetric P2₁/m within default distance tolerances. Herein a systematic investigation reveals that NaVO2F2 exists in at least four polymorphs: P2₁, (I), P2₁/m, (II), P2₁/c, (III), and one or more low-temperature ones. The new centrosymmetric modification, (III), with the space group P2₁/c has a similar atomic packing geometry to phase (I), except for having a doubled c axis. The double-cell of phase (III) arises from atomic shifts from the glide plane c at (x, ¼, z). With increasing temperature, the number of observed reflections decreases. The odd l reflections gradually become weaker and, correspondingly, all atoms shift towards the glide plane, resulting in a gradual second-order transformation of (III) into high-temperature phase (II) (P2₁/m) at below 493 K. At least one first-order enantiotropic phase transition was observed below 139 K from both the single-crystal X-ray diffraction and the differential scanning calorimetry analyses. Periodic first-principles calculations within density functional theory show that both P2₁/c superstructure (III) and P2₁ substructure (I) are more stable than P2₁/m structure (II), and that P2₁/c superstructure (III) is more stable that P2₁ substructure (I).

  10. Circadian ATP Release in Organotypic Cultures of the Rat Suprachiasmatic Nucleus Is Dependent on P2X7 and P2Y Receptors

    Czech Academy of Sciences Publication Activity Database

    Svobodová, Irena; Bhattacharya, Anirban; Ivetic, Milorad; Bendová, Z.; Zemková, Hana

    2018-01-01

    Roč. 9, Mar 6 (2018), č. článku 192. ISSN 1663-9812 R&D Projects: GA ČR(CZ) GA16-12695S; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : suprachiasmatic nucleus * organotypic cultures * astrocytes * P2X7 receptor * P2Y1 receptor * P2Y2 receptor * pannexin-1 hemichannel * ATP release Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 4.400, year: 2016

  11. 78 FR 31571 - Announcement of Requirements and Registration for the “Technology-based Products to Prevent High...

    Science.gov (United States)

    2013-05-24

    ... product can be accessible through (5 points). Quality of Product Performance (40 points maximum... Creating Opportunities to Meaningfully Promote Excellence in Technology, Education, and Science... design, performance, and developer's qualifications (for more detailed information, read the section...

  12. [ATP-P2X7R signalling pathway and its effects in parasitic diseases].

    Science.gov (United States)

    Wang-Fang, J; Chun-Jie, J; Fei, G; Jia-Hui, L; Ming, L

    2017-07-24

    ATP (Adenosine triphosphate) is an important endogenous damage - associated molecular pattern (DAMP). P2X 7 R is an ATP-gated cation channel. ATP-P2X 7 R plays a vital role in the pathophysiology of many diseases because P2X 7 R is distributed on various immune cells. ATP-P2X 7 R signal transduction pathway has been implicated to participate in the body's immune defense against pathogens. This paper reviews the recent progress regarding ATP-P2X 7 R and its effects on parasitic diseases.

  13. Direct Observation on Spin-Coating Process of PS- b -P2VP Thin Films

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Hiroki; Takenaka, Mikihito; Miyazaki, Tsukasa; Fujiwara, Akihiko; Lee, Byeongdu; Shimokita, Keisuke; Nishibori, Eiji; Takata, Masaki

    2016-05-10

    We studied the structural development of symmetric poly(styrene-b-2-vinylpyridine) (PS-b-P2VP) block copolymers during spin-coating using in situ grazing incidence small angle X-ray scattering (GISAXS) measurements. During the spin-coating process, after the formation of the micelles in dilute solution, the selective solvent induced two kinds of the morphological transition. Firstly, the disordered spherical micelles were transformed into a BCC lattice of spheres of which the (110) plane was oriented perpendicularly to the substrate surface. Secondly, further evaporation induced a transition from spheres on the BCC lattice into cylindrical structures. The orientation of the cylinders perpendicular to the substrate surface was induced by solvent convection perpendicular to the substrate, which occurs during rapid solvent evaporation. After this transition, vitrification of PS and P2VP prevented any further transition from cylinders to the more thermodynamically stable lamellar structures, as are generally observed as the bulk equilibrium state.

  14. Anisotropic thermal properties and ferroelectric phase transitions in layered CuInP2S6 and CuInP2Se6 crystals

    Science.gov (United States)

    Liubachko, V.; Shvalya, V.; Oleaga, A.; Salazar, A.; Kohutych, A.; Pogodin, A.; Vysochanskii, Yu. M.

    2017-12-01

    Thermal diffusivity and thermal conductivity have been studied for the layered crystals CuInP2S6, CuInP2Se6 from 30 K to 350 K, showing a relevant thermal anisotropy. Heat is much more efficiently transferred within the layers than perpendicular to them. The ferrielectric transition in CuInP2S6 is proven to be clearly first order while the ferroelectric one in CuInP2Se6 has a weak first order character. The behavior of the thermal conductivity as a function of temperature in the ferroelectric phases shows that heat conduction is phonon driven. Disorder in the paraelectric phases due to hopping motions of Cu ions significantly reduces the thermal conductivity to extremely low values.

  15. PI(4,5)P2-binding effector proteins for vesicle exocytosis

    Science.gov (United States)

    Martin, Thomas F. J.

    2014-01-01

    PI(4,5)P2 participates directly in priming and possibly fusion steps of Ca2+-triggered vesicle exocytosis. High concentration nanodomains of PI(4,5)P2 reside on the plasma membrane of neuroendocrine cells. A subset of vesicles that co-localize with PI(4,5)P2 domains appear to undergo preferential exocytosis in stimulated cells. PI(4,5)P2 directly regulates vesicle exocytosis by recruiting and activating PI(4,5)P2-binding proteins that regulate SNARE protein function including CAPS, Munc13-1/2, synaptotagmin-1, and other C2 domain-containing proteins. These PI(4,5)P2 effector proteins are coincidence detectors that engage in multiple interactions at vesicle exocytic sites. The SNARE protein syntaxin-1 also binds to PI(4,5)P2, which promotes clustering, but an activating role for PI(4,5)P2 in syntaxin-1 function remains to be fully characterized. Similar principles underlie polarized constitutive vesicle fusion mediated in part by the PI(4,5)P2-binding subunits of the exocyst complex (Sec3, Exo70). Overall, focal vesicle exocytosis occurs at sites landmarked by PI(4,5)P2, which serves to recruit and/or activate multifunctional PI(4,5)P2-binding proteins. PMID:25280637

  16. P2X7 receptor-deficient mice are susceptible to bone cancer pain

    DEFF Research Database (Denmark)

    Hansen, RR; Nielsen, CK; Nasser, A

    2011-01-01

    The purinergic P2X7 receptor is implicated in both neuropathic and inflammatory pain, and has been suggested as a possible target in pain treatment. However, the specific role of the P2X7 receptor in bone cancer pain is unknown. We demonstrated that BALB/cJ P2X7 receptor knockout (P2X7R KO) mice...... of the P2X7R KO mouse. Further experiments are needed to elucidate the exact role of the P2X7 receptors in bone cancer pain. Pain-related behaviours had an earlier onset in bone cancer-bearing, P2X7 receptor-deficient mice, and treatment with A-438079 failed to alleviate pain-related behaviours....

  17. P2X1 stimulation promotes thrombin receptor-mediated platelet aggregation.

    Science.gov (United States)

    Erhardt, J A; Toomey, J R; Douglas, S A; Johns, D G

    2006-04-01

    P2X1 receptors are ATP-gated channel demonstrated to be involved in multiple platelet responses, although in vitro analysis has been complicated by the effects of rapid desensitization. To further investigate potential roles of P2X1 receptors in platelet activation, the current study employed methods which maximally preserved P2X1 functionality. In preliminary in vivo studies, P2X1-deficiency reduced thrombus formation following the laser-induced, but not FeCl3-induced injury. Given the multiple potential mechanisms involved in thrombus formation in vivo, including tissue-factor/thrombin generation pathways, subsequent studies were designed to investigate the effects of P2X1 inhibition or stimulation on platelet activation in vitro; specifically, the interaction of P2X1 with thrombin receptor stimulation. Aggregation initiated by low/threshold levels of a protease-activated receptor (PAR)4 agonist was reduced in P2X1-deficient murine platelets, and inhibition of P2X1 in wild-type platelets similarly reduced PAR4-mediated aggregation. In human platelets, aggregation to low/threshold stimulation of PAR1 was inhibited with the P2X1 antagonist MRS2159. In addition, P2X1 stimulation primed human platelet responses, such that subsequent sub-threshold PAR1 responses were converted into significant aggregation. Selective ADP receptor inhibitors attenuated P2X1-mediated priming, suggesting that the synergy between P2X1 and sub-threshold PAR1 stimulation was in part because of enhanced granular release of ADP. Overall, the present study defines a novel interaction between platelet P2X1 and thrombin receptors, with P2X1 functioning to amplify aggregation responses at low levels of thrombin receptor stimulation.

  18. Potential role of P2X7R in esophageal squamous cell carcinoma proliferation.

    Science.gov (United States)

    Santos, André A; Cappellari, Angélica R; de Marchi, Fernanda O; Gehring, Marina P; Zaparte, Aline; Brandão, Caroline A; Lopes, Tiago Giuliani; da Silva, Vinicius D; Pinto, Luis Felipe Ribeiro; Savio, Luiz Eduardo Baggio; Moreira-Souza, Aline Cristina Abreu; Coutinho-Silva, Robson; Paccez, Juliano D; Zerbini, Luiz F; Morrone, Fernanda B

    2017-09-01

    Esophageal cancer is an aggressive tumor and is the sixth leading cause of cancer death worldwide. ATP is well known to regulate cancer progression in a variety of models by different mechanisms, including P2X7R activation. This study aimed to evaluate the role of P2X7R in esophageal squamous cell carcinoma (ESCC) proliferation. Our results show that treatment with high ATP concentrations induced a decrease in cell number, cell viability, number of polyclonal colonies, and reduced migration of ESCC. The treatment with the selective P2X7R antagonist A740003 or siRNA for P2X7 reverted this effect in the KYSE450 cell line. In addition, results showed that P2X7R is highly expressed, at mRNA and protein levels, in KYSE450 lineage. Additionally, KYSE450, KYSE30, and OE21 cells express P2X3R, P2X4R, P2X5R, P2X6R, and P2X7R genes. P2X1R is expressed by KYSE30 and KYSE450, and only KYSE450 expresses the P2X2R gene. Furthermore, esophageal cancer cell line KYSE450 presented higher expression of E-NTPDases 1 and 2 and of Ecto-5'-NT/CD73 when compared to normal cells. This cell line also exhibits ATPase, ADPase, and AMPase activity, although in different levels, and the co-treatment of apyrase was able to revert the antiproliferative effects of ATP. Moreover, results showed high immunostaining for P2X7R in biopsies of patients with esophageal carcinoma, indicating the involvement of this receptor in the growth of this type of cancer. The results suggest that P2X7R may be a potential pharmacological target to treat ESCC and can lead us to further investigate the effect of this receptor in cancer cell progression.

  19. Vascular surgical stretch injury leads to activation of P2X7 receptors and impaired endothelial function.

    Directory of Open Access Journals (Sweden)

    Padmini Komalavilas

    Full Text Available A viable vascular endothelial layer prevents vasomotor dysfunction, thrombosis, inflammation, and intimal hyperplasia. Injury to the endothelium occurs during harvest and "back table" preparation of human saphenous vein prior to implantation as an arterial bypass conduit. A subfailure overstretch model of rat aorta was used to show that subfailure stretch injury of vascular tissue leads to impaired endothelial-dependent relaxation. Stretch-induced impaired relaxation was mitigated by treatment with purinergic P2X7 receptor (P2X7R inhibitors, brilliant blue FCF (FCF and A740003, or apyrase, an enzyme that catalyzes the hydrolysis of ATP. Alternatively, treatment of rat aorta with exogenous ATP or 2'(3'-O-(4-Benzoyl benzoyl-ATP (BzATP also impaired endothelial-dependent relaxation. Treatment of human saphenous vein endothelial cells (HSVEC with exogenous ATP led to reduced nitric oxide production which was associated with increased phosphorylation of the stress activated protein kinase, p38 MAPK. ATP- stimulated p38 MAPK phosphorylation of HSVEC was inhibited by FCF and SB203580. Moreover, ATP inhibition of nitric oxide production in HSVEC was prevented by FCF, SB203580, L-arginine supplementation and arginase inhibition. Finally, L-arginine supplementation and arginase inhibition restored endothelial dependent relaxation after stretch injury of rat aorta. These results suggest that vascular stretch injury leads to ATP release, activation of P2X7R and p38 MAPK resulting in endothelial dysfunction due to arginase activation. Endothelial function can be restored in both ATP treated HSVEC and intact stretch injured rat aorta by P2X7 receptor inhibition with FCF or L-arginine supplementation, implicating straightforward therapeutic options for treatment of surgical vascular injury.

  20. Pollution prevention program implementation plan

    International Nuclear Information System (INIS)

    Engel, J.A.

    1996-09-01

    The Pollution Prevention Program Implementation Plan (the Plan) describes the Pacific Northwest National Laboratory's (PNNL) Pollution Prevention (P2) Program. The Plan also shows how the P2 Program at PNNL will be in support of and in compliance with the Hanford Site Waste Minimization and Pollution Prevention (WMin/P2) Awareness Program Plan and the Hanford Site Guide for Preparing and Maintaining Generator Group Pollution Prevention Program Documentation. In addition, this plan describes how PNNL will demonstrate compliance with various legal and policy requirements for P2. This plan documents the strategy for implementing the PNNL P2 Program. The scope of the P2 Program includes implementing and helping to implement P2 activities at PNNL. These activities will be implemented according to the Environmental Protection Agency's (EPA) hierarchy of source reduction, recycling, treatment, and disposal. The PNNL P2 Program covers all wastes generated at the Laboratory. These include hazardous waste, low-level radioactive waste, radioactive mixed waste, radioactive liquid waste system waste, polychlorinated biphenyl waste, transuranic waste, and sanitary waste generated by activities at PNNL. Materials, resource, and energy conservation are also within the scope of the PNNL P2 Program

  1. P2X receptors in the cardiovascular system and their potential as therapeutic targets in disease.

    Science.gov (United States)

    Ralevic, Vera

    2015-01-01

    This review considers the expression and roles of P2X receptors in the cardiovascular system in health and disease and their potential as therapeutic targets. P2X receptors are ligand gated ion channels which are activated by the endogenous ligand ATP. They are formed from the assembly of three P2X subunit proteins from the complement of seven (P2X1-7), which can associate to form homomeric or heteromeric P2X receptors. The P2X1 receptor is widely expressed in the cardiovascular system, being located in the heart, in the smooth muscle of the majority of blood vessels and in platelets. P2X1 receptors expressed in blood vessels can be activated by ATP coreleased with noradrenaline as a sympathetic neurotransmitter, leading to smooth muscle depolarisation and contraction. There is evidence that the purinergic component of sympathetic neurotransmission is increased in hypertension, identifying P2X1 receptors as a possible therapeutic target in this disorder. P2X3 and P2X2/3 receptors are expressed on cardiac sympathetic neurones and may, through positive feedback of neuronal ATP at this prejunctional site, amplify sympathetic neurotransmission. Activation of P2X receptors expressed in the heart increases cardiac myocyte contractility, and an important role of the P2X4 receptor in this has been identified. Deletion of P2X4 receptors in the heart depresses contractile performance in models of heart failure, while overexpression of P2X4 receptors has been shown to be cardioprotective, thus P2X4 receptors may be therapeutic targets in the treatment of heart disease. P2X receptors have been identified on endothelial cells. Although immunoreactivity for all P2X1-7 receptor proteins has been shown on the endothelium, relatively little is known about their function, with the exception of the endothelial P2X4 receptor, which has been shown to mediate endothelium-dependent vasodilatation to ATP released during shear stress. The potential of P2X receptors as therapeutic targets

  2. Methamphetamine alters microglial immune function through P2X7R signaling.

    Science.gov (United States)

    Fernandes, Nicole C; Sriram, Uma; Gofman, Larisa; Cenna, Jonathan M; Ramirez, Servio H; Potula, Raghava

    2016-04-26

    Purinoceptors have emerged as mediators of chronic inflammation and neurodegenerative processes. The ionotropic purinoceptor P2X7 (P2X7R) is known to modulate proinflammatory signaling and integrate neuronal-glial circuits. Evidence of P2X7R involvement in neurodegeneration, chronic pain, and chronic inflammation suggests that purinergic signaling plays a major role in microglial activation during neuroinflammation. In this study, we investigated the effects of methamphetamine (METH) on microglial P2X7R. ESdMs were used to evaluate changes in METH-induced P2X7R gene expression via Taqman PCR and protein expression via western blot analysis. Migration and phagocytosis assays were used to evaluate functional changes in ESdMs in response to METH treatment. METH-induced proinflammatory cytokine production following siRNA silencing of P2X7R in ESdMs measured P2X7R-dependent functional changes. In vivo expression of P2X7R and tyrosine hydroxylase (TH) was visualized in an escalating METH dose mouse model via immunohistochemical analysis. Stimulation of ESdMs with METH for 48 h significantly increased P2X7R mRNA (*p P2X7R protein in cellular fractionations revealed increases in membrane P2X7R (*p P2X7R-dependent through the use of A 438079, a P2X7R-competitive antagonist, which reversed the METH effects (****p P2X7R antagonist reduced METH-induced phagocytosis (****p P2X7R decreased TNF-α (*p P2X7R and decreased TH expression in the striata of escalating dose METH animal model compared to controls. This study sheds new light on the functional role of P2X7R in the regulation of microglial effector functions during substance abuse. Our findings suggest that P2X7R plays an important role in METH-induced microglial activation responses. P2X7R antagonists may thus constitute a novel target of therapeutic utility in neuroinflammatory conditions by regulating pathologically activated glial cells in stimulant abuse.

  3. A haplotype spanning P2X7R, P2X4R and CAMKK2 may mark susceptibility to pulmonary non-tuberculous mycobacterial disease.

    Science.gov (United States)

    Halstrom, Samuel; Cherry, Catherine L; Black, Michael; Thomson, Rachel; Goullee, Hayley; Baltic, Svetlana; Allcock, Richard; Temple, Suzanna E L; Price, Patricia

    2017-05-01

    Despite widespread exposure to potentially pathogenic mycobacteria present in the soil and in domestic water supplies, it is not clear why only a small proportion of individuals contract pulmonary nontuberculous mycobacterial (NTM) infections. Here, we explore the impact of polymorphisms within three genes: P2X ligand gated ion channel 7 (P2X7R), P2X ligand gated ion channel 4 (P2X4R) and calcium/calmodulin-dependent protein kinase kinase 2 beta (CAMKK2) on susceptibility. Thirty single nucleotide polymorphisms (SNPs) were genotyped in NTM patients (n = 124) and healthy controls (n = 229). Weak associations were found between individual alleles in P2X7R and disease but were not significant in multivariate analyses adjusted to account for gender. Haplotypes spanning the three genes were derived using the fastPHASE algorithm. This yielded 27 haplotypes with frequencies >1% and accounting for 63.3% of the combined cohort. In univariate analyses, seven of these haplotypes displayed associations with NTM disease above our preliminary cut-off (p ≤ 0.20). When these were carried forward in a logistic regression model, gender and one haplotype (SH95) were independently associated with the disease (model p P2X7R and CAMKK2 in pathways affecting pulmonary NTM disease.

  4. ATP and UTP responses of cultured rat aortic smooth muscle cells revisited: dominance of P2Y2 receptors

    Science.gov (United States)

    Kumari, Rajendra; Goh, Gareth; Ng, Leong L; Boarder, Michael R

    2003-01-01

    It has previously been shown that ATP and UTP stimulate P2Y receptors in vascular smooth muscle cells (VSMCs), but the nature of these receptors, in particular the contribution of P2Y2 and P2Y4 subtypes, has not been firmly established. Here we undertake a further pharmacological analysis of [3H]inositol polyphosphate responses to nucleotides in cultured rat VSMCs. ATP generated a response that was partial compared to UTP, as reported earlier. In the presence of a creatine phosphokinase (CPK) system for regenerating nucleoside triphosphates, the response to ATP was increased, the response to UTP was unchanged, and the difference between UTP and ATP concentration–response curves disappeared. Chromatographic analysis showed that ATP was degraded slightly faster than UTP. The response to UDP was always smaller than that to UTP, but with a shallow slope and a high potency component. In the presence of hexokinase (which prevents the accumulation of ATP/UTP from ADP/UDP), the maximum response to UDP was reduced and the high-potency component of the curve was retained. By contrast, the response to ADP was weaker throughout in the presence of hexokinase. ATPγS was an effective agonist with a similar EC50 to UTP, but with a lower maximum. ITP was a weak agonist compared with UTP. Suramin was an effective antagonist of the response to UTP (pA2=4.48), but not when ATP was the agonist. However, suramin was an effective antagonist (pA2=4.45) when stimulation with ATP was in the presence of the CPK regenerating system. Taken together with the results of others, these findings indicate that the response of cultured rat VSMCs to UTP and to ATP is predominantly at the P2Y2 receptor, and that there is also a response to UDP at the P2Y6 receptor. PMID:14597595

  5. Communication Technology Used among Parents and Their College Teens: Implications for College Health Promotion and Risk Prevention Programs

    Science.gov (United States)

    Abar, Caitlin C.; Abar, Beau; Turrisi, Robert; Belden, Calum

    2013-01-01

    The current study examined the nature of parent-teen communication in college to re-evaluate the potential for parent inclusion in college success and risk prevention programs. During September 2006, 290 first-year college students were assessed for the frequency and form (e.g., cell phone, e-mail, text) of communication with their parents. Latent…

  6. Interest in use of mHealth technology in HIV prevention and associated factors among high-risk drug users enrolled in methadone maintenance program.

    Science.gov (United States)

    Shrestha, Roman; Karki, Pramila; Copenhaver, Michael

    2017-09-01

    The adoption of mobile technologies for health (mHealth) in healthcare has grown considerably in recent years, but systematic assessment of interest in the use of mHealth in HIV prevention efforts among people who use drugs (PWUD) is lacking. We therefore examined interest in use of mHealth technology in HIV prevention and associated individual-level factors among high-risk PWUD enrolled in methadone maintenance program. A total of 400 HIV-negative PWUD, who reported drug- and/or sex-related risk behaviors completed a standardized assessment using audio computer assisted self-interview (ACASI). Results revealed significant interest in using mHealth-based approaches for specific purposes, including: to receive medication reminders (72.3%), to receive information about HIV risk reduction (65.8%), and to assess HIV risk behaviors (76.5%). Multivariate analysis showed that interest in receiving medication reminders was associated with currently taking medication and being neurocognitively impaired, whereas interest in receiving HIV-risk reduction information was associated with being non-white, married, and perceiving the person was at high-risk for contracting HIV. Similarly, participants' interested in using mHealth for HIV risk behavior assessment was associated with having recently visited a healthcare provider and exhibiting depressive symptoms. Overall, this study demonstrated that high-risk PWUD are interested in using mHealth-based tools as a key part of an HIV prevention approach within a common type of drug treatment settings. Thus, formative research on preferences for design and functionality of mHealth-based HIV prevention tools are now needed, followed by practical development, implementation, and evaluation of these new intervention strategies.

  7. Amplification loop of the inflammatory process is induced by P2X7R activation in intestinal epithelial cells in response to neutrophil transepithelial migration.

    Science.gov (United States)

    Cesaro, Annabelle; Brest, Patrick; Hofman, Véronique; Hébuterne, Xavier; Wildman, Scott; Ferrua, Bernard; Marchetti, Sandrine; Doglio, Alain; Vouret-Craviari, Valérie; Galland, Franck; Naquet, Philippe; Mograbi, Baharia; Unwin, Robert; Hofman, Paul

    2010-07-01

    Inflammatory bowel diseases (IBD) are characterized during their active phase by polymorphonuclear leukocyte (PMNL) transepithelial migration. The efflux of PMNL into the mucosa is associated with the production of proinflammatory cytokines and the release of ATP from damaged and necrotic cells. The expression and function of purinergic P2X(7) receptor (P2X(7)R) in intestinal epithelial cells (IEC) and its potential role in the "cross talk" between IEC and PMNL have not been explored. The aims of the present study were 1) to examine P2X(7)R expression in IEC (T84 cells) and in human intestinal biopsies; 2) to detect any changes in P2X(7)R expression in T84 cells during PMNL transepithelial migration, and during the active and quiescent phases of IBD; and 3) to test whether P2X(7)R stimulation in T84 monolayers can induce caspase-1 activation and IL-1beta release by IEC. We found that a functional ATP-sensitive P2X(7)R is constitutively expressed at the apical surface of IEC T84 cells. PMNL transmigration regulates dynamically P2X(7)R expression and alters its distribution from the apical to basolateral surface of IEC during the early phase of PMNL transepithelial migration in vitro. P2X(7)R expression was weak in intestinal biopsies obtained during the active phase of IBD. We show that activation of epithelial P2X(7)R is mandatory for PMNL-induced caspase-1 activation and IL-1beta release by IEC. Overall, these changes in P2X(7)R function may serve to tailor the intensity of the inflammatory response and to prevent IL-1beta overproduction and inflammatory disease.

  8. Post-translational regulation of P2X receptor channels: modulation by phospholipids

    Directory of Open Access Journals (Sweden)

    Louis-Philippe eBernier

    2013-11-01

    Full Text Available P2X receptor channels mediate fast excitatory signaling by ATP and play major roles in sensory transduction, neuro-immune communication and inflammatory response. P2X receptors constitute a gene family of calcium-permeable ATP-gated cation channels therefore the regulation of P2X signaling is critical for both membrane potential and intracellular calcium homeostasis. Phosphoinositides (PIPn are anionic signaling phospholipids that act as functional regulators of many types of ion channels. Direct PIPn binding was demonstrated for several ligand- or voltage-gated ion channels, however no generic motif emerged to accurately predict lipid-protein binding sites. This review presents what is currently known about the modulation of the different P2X subtypes by phospholipids and about critical determinants underlying their sensitivity to PIPn levels in the plasma membrane.All functional mammalian P2X subtypes tested, with the notable exception of P2X5, have been shown to be positively modulated by PIPn, i.e. homomeric P2X1, P2X2, P2X3, P2X4, and P2X7, as well as heteromeric P2X1/5 and P2X2/3 receptors. Based on various results reported on the aforementioned subtypes including mutagenesis of the prototypical PIPn-sensitive P2X4 and PIPn-insensitive P2X5 receptor subtypes, an increasing amount of functional, biochemical and structural evidence converges on the modulatory role of a short polybasic domain located in the proximal C-terminus of P2X subunits. This linear motif, semi-conserved in the P2X family, seems necessary and sufficient for encoding direct modulation of ATP-gated channels by PIPn. Furthermore, the physiological impact of the regulation of ionotropic purinergic responses by phospholipids on pain pathways was recently revealed in the context of native crosstalks between phospholipase C-linked metabotropic receptors and P2X receptor channels in DRG sensory neurons and microglia.

  9. Glutathione induces GABA release through P2X7R activation on Müller glia.

    Science.gov (United States)

    Freitas, Hércules Rezende; Reis, Ricardo A de Melo

    2017-01-01

    The retinal tissue of warm-blooded vertebrates performs surprisingly complex and accurate transduction of visual information. To achieve precision, a multilayered neuroglia structure is established throughout the embryonic development, and the presence of radial Müller (glial) cells ensure differentiation, growth and survival for the neuronal elements within retinal environment. It is assumed that Müller cells serve as a dynamic reservoir of progenitors, capable of expressing transcription factors, differentiating and proliferating as either neuronal or glial cells depending on extrinsic cues. In the postnatal period, Müller glia may re-enter cell cycle and produce new retinal neurons in response to acute damage. In this context, glutathione (GSH), a virtually ubiquitous tripeptide antioxidant, which is found at milimolar concentrations in central glial cells, plays a vital role as a reducing agent, buffering radical oxygen species (ROS) and preventing cell death in severely injured retinal tissues. Despite its antioxidant role, data also point to GSH as a signaling agent, suggesting that GABA release and P2X 7 R-mediated calcium inwards occur in Müller cells in a GSH-enriched environment. These phenomena indicate a novel mechanistic response to damage in the vertebrate retinal tissue, particularly in neuron-glia networks.

  10. Challenges and opportunities for controlling and preventing animal diseases in developing countries through gene-based technologies

    International Nuclear Information System (INIS)

    Crowther, J.R.; Jeggo, M.H.

    2005-01-01

    Polymerase Chain Reaction (PCR) technology allows scientist to amplify, copy, identify, characterize and manipulate genes in a relatively simple way. Exploitation of the technology to devise new products and translate these to the commercial sector has been remarkable. Molecular technologies are not difficult to establish and use, and can appear to offer developing countries many opportunities. However, developing countries should look in a different way at the apparent advantages offered. Whilst molecular biological science appears to offer solutions to many problems, there are a number of drawbacks. This desire to adopt the latest technology often overrides any considerations of the use of more conventional technologies to address needs. The conventional, and often more practical, methods already provide many specific tools in the disease control area. Changing the technology can also deflect critical resources into the molecular field in terms of laboratory funding and training. This may cause redundancy of staff, limit further development in conventional techniques, and polarize scientists into the older (less glossy) and newer (molecular) camps. Animal disease diagnosis still primarily utilizes conventional techniques such as Enzyme Linked Immunosorbent Assay (ELISA). This will not change drastically in developing countries, but developments will combine such methods with more discriminatory molecular techniques, and a balanced and parallel development is needed. An understanding of the use and possible advantages of the various technologies is required by both scientists and policy-makers in developing nations. Vaccines based on molecular science could have a real impact in developing countries, but 'vaccinology' needs to examine both the animal (immunology of target species) and the disease agent itself. This is a research-based science and, as such, is expensive, with no surety of success. Developing countries should exploit links with developed countries

  11. Macrophage activation and polarization modify P2X7 receptor secretome influencing the inflammatory process.

    Science.gov (United States)

    de Torre-Minguela, Carlos; Barberà-Cremades, Maria; Gómez, Ana I; Martín-Sánchez, Fátima; Pelegrín, Pablo

    2016-03-03

    The activation of P2X7 receptor (P2X7R) on M1 polarized macrophages induces the assembly of the NLRP3 inflammasome leading to the release of pro-inflammatory cytokines and the establishment of the inflammatory response. However, P2X7R signaling to the NLRP3 inflammasome is uncoupled on M2 macrophages without changes on receptor activation. In this study, we analyzed P2X7R secretome in wild-type and P2X7R-deficient macrophages polarized either to M1 or M2 and proved that proteins released after P2X7R stimulation goes beyond caspase-1 secretome. The characterization of P2X7R-secretome reveals a new function of this receptor through a fine-tuning of protein release. We found that P2X7R stimulation in macrophages is able to release potent anti-inflammatory proteins, such as Annexin A1, independently of their polarization state suggesting for first time a potential role for P2X7R during resolution of the inflammation and not linked to the release of pro-inflammatory cytokines. These results are of prime importance for the development of therapeutics targeting P2X7R.

  12. A Methodology for Validating Safety Heuristics Using Clinical Simulations: Identifying and Preventing Possible Technology-Induced Errors Related to Using Health Information Systems

    Science.gov (United States)

    Borycki, Elizabeth; Kushniruk, Andre; Carvalho, Christopher

    2013-01-01

    Internationally, health information systems (HIS) safety has emerged as a significant concern for governments. Recently, research has emerged that has documented the ability of HIS to be implicated in the harm and death of patients. Researchers have attempted to develop methods that can be used to prevent or reduce technology-induced errors. Some researchers are developing methods that can be employed prior to systems release. These methods include the development of safety heuristics and clinical simulations. In this paper, we outline our methodology for developing safety heuristics specific to identifying the features or functions of a HIS user interface design that may lead to technology-induced errors. We follow this with a description of a methodological approach to validate these heuristics using clinical simulations. PMID:23606902

  13. Membrane Order Is a Key Regulator of Divalent Cation-Induced Clustering of PI(3,5)P2and PI(4,5)P2.

    Science.gov (United States)

    Sarmento, Maria J; Coutinho, Ana; Fedorov, Aleksander; Prieto, Manuel; Fernandes, Fábio

    2017-10-31

    Although the evidence for the presence of functionally important nanosized phosphorylated phosphoinositide (PIP)-rich domains within cellular membranes has accumulated, very limited information is available regarding the structural determinants for compartmentalization of these phospholipids. Here, we used a combination of fluorescence spectroscopy and microscopy techniques to characterize differences in divalent cation-induced clustering of PI(4,5)P 2 and PI(3,5)P 2 . Through these methodologies we were able to detect differences in divalent cation-induced clustering efficiency and cluster size. Ca 2+ -induced PI(4,5)P 2 clusters are shown to be significantly larger than the ones observed for PI(3,5)P 2 . Clustering of PI(4,5)P 2 is also detected at physiological concentrations of Mg 2+ , suggesting that in cellular membranes, these molecules are constitutively driven to clustering by the high intracellular concentration of divalent cations. Importantly, it is shown that lipid membrane order is a key factor in the regulation of clustering for both PIP isoforms, with a major impact on cluster sizes. Clustered PI(4,5)P 2 and PI(3,5)P 2 are observed to present considerably higher affinity for more ordered lipid phases than the monomeric species or than PI(4)P, possibly reflecting a more general tendency of clustered lipids for insertion into ordered domains. These results support a model for the description of the lateral organization of PIPs in cellular membranes, where both divalent cation interaction and membrane order are key modulators defining the lateral organization of these lipids.

  14. Synthesis of CaO-SiO2-P2O5 mesoporous bioactive glasses with high P2O5 content by evaporation induced self assembly process.

    Science.gov (United States)

    Zhao, Shan; Li, Yanbao; Li, Dongxu

    2011-02-01

    Mesoporous bioactive glasses (MBGs) of the CaO-SiO(2)-P(2)O(5) system containing relatively high P(2)O(5) contents (10-30 mol%) were prepared from a sol-gel. An evaporation-induced self-assembly (EISA) technique was used with poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (EO(20)-PO(70)-EO(20), P123) acting as a template. The structural, morphological and textural properties of MBGs were investigated by small-angle X-ray diffraction (SAXRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and a N(2) sorption/desorption technique. SAXRD and TEM results display the reduced long-range ordering of mesopores with increasing P(2)O(5) content. N(2) sorption/desorption analysis shows that all three samples exhibit a type IV isotherm with type H1 hysteresis loops, characteristic of independent cylindrical slim pore channels and this material has a Barret-Joyner-Halenda (BJH) model pore size of ~4 nm and BET specific surface area ~430 m(2)/g. NMR results indicate a more condensed framework for samples with 30 mol% P(2)O(5) than samples with 10 mol% P(2)O(5). For in vitro bioactivity tests where samples were soaked in simulated body fluid (SBF), samples with 30 mol% P(2)O(5) showed higher crystallinity than those with lower P(2)O(5) contents Silicon concentration increased in SBF solution during the soaking period, which indicates MBGs can be degradable in SBF solution.

  15. Activation of P2Y6 Receptors Facilitates Nonneuronal Adenosine Triphosphate and Acetylcholine Release from Urothelium with the Lamina Propria of Men with Bladder Outlet Obstruction.

    Science.gov (United States)

    Silva, Isabel; Ferreirinha, Fátima; Magalhães-Cardoso, Maria Teresa; Silva-Ramos, Miguel; Correia-de-Sá, Paulo

    2015-10-01

    Deregulation of purinergic bladder signaling may contribute to persistent detrusor overactivity in patients with bladder outlet obstruction. Activation of uridine diphosphate sensitive P2Y6 receptors increases voiding frequency in rats indirectly by releasing adenosine triphosphate from the urothelium. To our knowledge this mechanism has never been tested in the human bladder. We examined the role of the uridine diphosphate sensitive P2Y6 receptor on tetrodotoxin insensitive nonneuronal adenosine triphosphate and [(3)H]acetylcholine release from the human urothelium with the lamina propria of control organ donors and patients with benign prostatic hyperplasia. The adenosine triphosphate-to-[(3)H]acetylcholine ratio was fivefold higher in mucosal urothelium/lamina propria strips from benign prostatic hyperplasia patients than control men. The selective P2Y6 receptor agonist PSB0474 (100 nM) augmented by a similar amount adenosine triphosphate and [(3)H]acetylcholine release from mucosal urothelium/lamina propria strips from both groups of individuals. The facilitatory effect of PSB0474 was prevented by MRS2578 (50 nM) and by carbenoxolone (10 μM), which block P2Y6 receptor and pannexin-1 hemichannels, respectively. Blockade of P2X3 (and/or P2X2/3) receptors with A317491 (100 nM) also attenuated release facilitation by PSB0474 in control men but not in patients with benign prostatic hyperplasia. Immunolocalization studies showed that P2Y6, P2X2 and P2X3 receptors were present in choline acetyltransferase positive urothelial cells. In contrast to P2Y6 staining, choline acetyltransferase, P2X2 and P2X3 immunoreactivity decreased in the urothelium of benign prostatic hyperplasia patients. Activation of P2Y6 receptor amplifies mucosal adenosine triphosphate release underlying bladder overactivity in patients with benign prostatic hyperplasia. Therefore, we propose selective P2Y6 receptor blockade as a novel therapeutic strategy to control persistent storage symptoms in

  16. Health Technology Assessment of Medical Interventions in the Prevention and Treatment of Disease: Directions of Further Research and Policy Implications

    NARCIS (Netherlands)

    C.M. Galani (Carmen)

    2009-01-01

    textabstractHealth technology assessment (HTA) originated from the spread of costly medical equipment and growing concerns over the ability and willingness of taxpayers and health insurers to pay for them. The main aim of HTA is to provide a range of stakeholders, typically those involved in

  17. Anticipatory Eco-Design Strategies for Smart Textiles : Perspectives on environmental risk prevention in the development of an emerging technology

    NARCIS (Netherlands)

    Köhler, A.R.

    2013-01-01

    This dissertation explores environmental aspects of smart textiles: products that feature a deep integration or even a fusion of textile and electronic materials. The emerging technology exemplifies a contemporary innovation trend of augmenting the functionality of every-day objects to make them

  18. The Use of Behavior Change Techniques and Theory in Technologies for Cardiovascular Disease Prevention and Treatment in Adults: A Comprehensive Review.

    Science.gov (United States)

    Winter, Sandra J; Sheats, Jylana L; King, Abby C

    2016-01-01

    This review examined the use of health behavior change techniques and theory in technology-enabled interventions targeting risk factors and indicators for cardiovascular disease (CVD) prevention and treatment. Articles targeting physical activity, weight loss, smoking cessation and management of hypertension, lipids and blood glucose were sourced from PubMed (November 2010-2015) and coded for use of 1) technology, 2) health behavior change techniques (using the CALO-RE taxonomy), and 3) health behavior theories. Of the 984 articles reviewed, 304 were relevant (240=intervention, 64=review). Twenty-two different technologies were used (M=1.45, SD=+/-0.719). The most frequently used behavior change techniques were self-monitoring and feedback on performance (M=5.4, SD=+/-2.9). Half (52%) of the intervention studies named a theory/model - most frequently Social Cognitive Theory, the Trans-theoretical Model, and the Theory of Planned Behavior/Reasoned Action. To optimize technology-enabled interventions targeting CVD risk factors, integrated behavior change theories that incorporate a variety of evidence-based health behavior change techniques are needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Expression of P2X7R in breast cancer tissue and the induction of apoptosis by the gene-specific shRNA in MCF-7 cells.

    Science.gov (United States)

    Tan, Chao; Han, L I; Zou, Lili; Luo, Chunhua; Liu, Aihua; Sheng, Xiejing; Xi, Dee

    2015-10-01

    significantly reduced rates of proliferation when compared with the normal control group. In addition, flow cytometry revealed that the P2X7R-shRNA and KN-62 groups exhibited a reduced level of cell proliferation and a higher rate of apoptosis. In conclusion, P2X7R was shown to be overexpressed in breast cancer tissues and positively associated with ER expression. A P2X7R-shRNA expression vector effectively inhibited P2X7R expression in MCF-7 breast cancer cells, which subsequently induced cell apoptosis and reduced the levels of cell proliferation. These results indicated that P2X7R may serve as a potential target for breast cancer treatment and prevention.

  20. Protein kinase C isoforms in bovine aortic endothelial cells: role in regulation of P2Y- and P2U-purinoceptor-stimulated prostacyclin release.

    Science.gov (United States)

    Patel, V; Brown, C; Boarder, M R

    1996-05-01

    1. Enhanced synthesis of prostacyclin (PGI2) and inositol polyphosphates in bovine aortic endothelial cells in response to ATP and ADP is mediated by co-existing P2Y- and P2U-purinoceptors. Here we examine the regulation of these responses by isoforms of protein kinase C (PKC). 2. Immunoblots with antisera specific for 8 different PKC isoforms revealed the presence of alpha, epsilon and zeta, while no immunoreactivity was found for beta, gamma, delta, eta and theta isoforms. PKC-alpha was largely cytosolic in unstimulated cells and almost all translocated to the membrane (Triton X-100 soluble) after a 1 min treatment with the PKC activating phorbol myristate acetate (PMA); PKC-epsilon was always in a Triton X-100 insoluble membrane fraction, while PKC-zeta was found in both soluble and membrane bound (Triton X-100 soluble) forms in the unstimulated cells and was unaffected by PMA. 3. Treatment with PMA for 6 h led to a 90% downregulation of PKC-alpha, while the immunoreactivity to the epsilon and zeta isoforms remained largely unchanged. 4. After either 10 min or 6 h exposure to PMA the PGI2 response to activation of both receptors was enhanced, while the inositol 1,4,5-trisphosphate response to P2Y-purinoceptor activation was substantially attenuated and the P2U-purinoceptor response was unchanged. Thus the PGI2 response to PMA under conditions when 90% of the PKC-alpha was lost resembles that seen on acute stimulation of PKC by PMA, and the PGI2 response does not correlate with phospholipase C response. 5. Inhibition of PKC with the isoform non-selective inhibitors, Ro 31-8220 and Go 6850 abolished the PGI2 response to both P2U- and P2Y-purinoceptor stimulation. However, Go 6976, which preferentially inhibits Ca2+ sensitive isoforms (such as PKC-alpha) and not Ca2+ insensitive isoforms (such as PKC-epsilon), had no effect on the PGI2 response. 6. The results show that there is a requirement for PKC in the stimulation of PGI2 production by endothelial P2Y- and P2U

  1. P2Y Receptors in Synaptic Transmission and Plasticity: Therapeutic Potential in Cognitive Dysfunction

    Directory of Open Access Journals (Sweden)

    Segundo J. Guzman

    2016-01-01

    Full Text Available ATP released from neurons and astrocytes during neuronal activity or under pathophysiological circumstances is able to influence information flow in neuronal circuits by activation of ionotropic P2X and metabotropic P2Y receptors and subsequent modulation of cellular excitability, synaptic strength, and plasticity. In the present paper we review cellular and network effects of P2Y receptors in the brain. We show that P2Y receptors inhibit the release of neurotransmitters, modulate voltage- and ligand-gated ion channels, and differentially influence the induction of synaptic plasticity in the prefrontal cortex, hippocampus, and cerebellum. The findings discussed here may explain how P2Y1 receptor activation during brain injury, hypoxia, inflammation, schizophrenia, or Alzheimer’s disease leads to an impairment of cognitive processes. Hence, it is suggested that the blockade of P2Y1 receptors may have therapeutic potential against cognitive disturbances in these states.

  2. Are Virtual Rehabilitation Technologies Feasible Models to Scale an Evidence-Based Fall Prevention Program? A Pilot Study Using the Kinect Camera.

    Science.gov (United States)

    Shubert, Tiffany E; Basnett, Jeanna; Chokshi, Anang; Barrett, Mark; Komatireddy, Ravi

    2015-11-05

    Falls in older adults are a significant public health issue. Interventions have been developed and proven effective to reduce falls in older adults, but these programs typically last several months and can be resource intensive. Virtual rehabilitation technologies may offer a solution to bring these programs to scale. Off-the-shelf and custom exergames have demonstrated to be a feasible adjunct to rehabilitation with older adults. However, it is not known if older adults will be able or willing to use a virtual rehabilitation technology to participate in an evidence-based fall prevention program. To have the greatest impact, virtual rehabilitation technologies need to be acceptable to older adults from different backgrounds and level of fall risk. If these technologies prove to be a feasible option, they offer a new distribution channel to disseminate fall prevention programs. Stand Tall (ST) is a virtual translation of the Otago Exercise Program (OEP), an evidence-based fall prevention program. Stand Tall was developed using the Virtual Exercise Rehabilitation Assistant (VERA) software, which uses a Kinect camera and a laptop to deliver physical therapy exercise programs. Our purpose in this pilot study was to explore if ST could be a feasible platform to deliver the OEP to older adults from a variety of fall risk levels, education backgrounds, and self-described level of computer expertise. Adults age 60 and over were recruited to participate in a one-time usability study. The study included orientation to the program, navigation to exercises, and completion of a series of strength and balance exercises. Quantitative analysis described participants and the user experience. A diverse group of individuals participated in the study. Twenty-one potential participants (14 women, 7 men) met the inclusion criteria. The mean age was 69.2 (± 5.8) years, 38% had a high school education, 24% had a graduate degree, and 66% classified as "at risk for falls". Eighteen

  3. P2Y6 Receptor Activation Promotes Inflammation and Tissue Remodeling in Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Tobias Müller

    2017-08-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a disease with a poor prognosis and very few available treatment options. The involvement of the purinergic receptor subtypes P2Y2 and P2X7 in fibrotic lung disease has been demonstrated recently. In this study, we investigated the role of P2Y6 receptors in the pathogenesis of IPF in humans and in the animal model of bleomycin-induced lung injury. P2Y6R expression was upregulated in lung structural cells but not in bronchoalveolar lavage (BAL cells derived from IPF patients as well as in animals following bleomycin administration. Furthermore, BAL fluid levels of the P2Y6R agonist uridine-5′-diphosphate were elevated in animals with bleomycin-induced pulmonary fibrosis. Inflammation and fibrosis following bleomycin administration were reduced in P2Y6R-deficient compared to wild-type animals confirming the pathophysiological relevance of P2Y6R subtypes for fibrotic lung diseases. Experiments with bone marrow chimeras revealed the importance of P2Y6R expression on lung structural cells for pulmonary inflammation and fibrosis. Similar effects were obtained when animals were treated with the P2Y6R antagonist MRS2578. In vitro studies demonstrated that proliferation and secretion of the pro-inflammatory/pro-fibrotic cytokine IL-6 by lung fibroblasts are P2Y6R-mediated processes. In summary, our results clearly demonstrate the involvement of P2Y6R subtypes in the pathogenesis of pulmonary fibrosis. Thus, blocking pulmonary P2Y6 receptors might be a new target for the treatment of IPF.

  4. Novel protective role of endogenous cardiac myocyte P2X4 receptors in heart failure.

    Science.gov (United States)

    Yang, Tiehong; Shen, Jian-bing; Yang, Ronghua; Redden, John; Dodge-Kafka, Kimberly; Grady, James; Jacobson, Kenneth A; Liang, Bruce T

    2014-05-01

    Heart failure (HF), despite continuing progress, remains a leading cause of mortality and morbidity. P2X4 receptors (P2X4R) have emerged as potentially important molecules in regulating cardiac function and as potential targets for HF therapy. Transgenic P2X4R overexpression can protect against HF, but this does not explain the role of native cardiac P2X4R. Our goal is to define the physiological role of endogenous cardiac myocyte P2X4R under basal conditions and during HF induced by myocardial infarction or pressure overload. Mice established with conditional cardiac-specific P2X4R knockout were subjected to left anterior descending coronary artery ligation-induced postinfarct or transverse aorta constriction-induced pressure overload HF. Knockout cardiac myocytes did not show P2X4R by immunoblotting or by any response to the P2X4R-specific allosteric enhancer ivermectin. Knockout hearts showed normal basal cardiac function but depressed contractile performance in postinfarct and pressure overload models of HF by in vivo echocardiography and ex vivo isolated working heart parameters. P2X4R coimmunoprecipitated and colocalized with nitric oxide synthase 3 (eNOS) in wild-type cardiac myocytes. Mice with cardiac-specific P2X4R overexpression had increased S-nitrosylation, cyclic GMP, NO formation, and were protected from postinfarct and pressure overload HF. Inhibitor of eNOS, L-N(5)-(1-iminoethyl)ornithine hydrochloride, blocked the salutary effect of cardiac P2X4R overexpression in postinfarct and pressure overload HF as did eNOS knockout. This study establishes a new protective role for endogenous cardiac myocyte P2X4R in HF and is the first to demonstrate a physical interaction between the myocyte receptor and eNOS, a mediator of HF protection. © 2014 American Heart Association, Inc.

  5. Methamphetamine alters microglial immune function through P2X7R signaling

    OpenAIRE

    Fernandes, Nicole C.; Sriram, Uma; Gofman, Larisa; Cenna, Jonathan M.; Ramirez, Servio H.; Potula, Raghava

    2016-01-01

    Background Purinoceptors have emerged as mediators of chronic inflammation and neurodegenerative processes. The ionotropic purinoceptor P2X7 (P2X7R) is known to modulate proinflammatory signaling and integrate neuronal-glial circuits. Evidence of P2X7R involvement in neurodegeneration, chronic pain, and chronic inflammation suggests that purinergic signaling plays a major role in microglial activation during neuroinflammation. In this study, we investigated the effects of methamphetamine (MET...

  6. Purinergic receptor P2RY12-dependent microglial closure of the injured blood-brain barrier

    DEFF Research Database (Denmark)

    Lou, Nanhong; Takano, Takahiro; Pei, Yong

    2016-01-01

    Microglia are integral functional elements of the central nervous system, but the contribution of these cells to the structural integrity of the neurovascular unit has not hitherto been assessed. We show here that following blood-brain barrier (BBB) breakdown, P2RY12 (purinergic receptor P2Y, G......-protein coupled, 12)-mediated chemotaxis of microglia processes is required for the rapid closure of the BBB. Mice treated with the P2RY12 inhibitor clopidogrel, as well as those in which P2RY12 was genetically ablated, exhibited significantly diminished movement of juxtavascular microglial processes and failed...

  7. Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor

    Directory of Open Access Journals (Sweden)

    Elias Leiva-Salcedo

    2011-01-01

    Full Text Available The purinergic P2X7 receptor (P2X7R plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS is one of the strongest stimuli of the immune response, and it has been shown that P2X7R activation can modulate LPS-induced responses. Moreover, a C-terminal binding site for LPS has been proposed. In order to evaluate if LPS can directly modulate the activity of the P2X7R, we tested several signaling pathways associated with P2X7R activation in HEK293 cells that do not express the TLR-4 receptor. We found that LPS alone was unable to induce any P2X7R-related activity, suggesting that the P2X7R is not directly activated by the endotoxin. On the other hand, preapplication of LPS inhibited ATP-induced currents, intracellular calcium increase, and ethidium bromide uptake and had no effect on ERK activation in HEK293 cells. In splenocytes-derived T-regulatory cells, in which ATP-induced apoptosis is driven by the P2X7R, LPS inhibited ATP-induced apoptosis. Altogether, these results demonstrate that LPS modulates the activity of the P2X7R and suggest that this effect could be of physiological relevance.

  8. Microglia P2Y6 receptor is related to Parkinson’s disease through neuroinflammatory process

    Directory of Open Access Journals (Sweden)

    Xiaodong Yang

    2017-02-01

    Full Text Available Abstract Background Microglia in the central nervous system (CNS were reported to play crucial role in neurodegeneration. Previous studies showed that P2Y6 receptor (P2Y6R mainly contributed to microglia activation and phagocytosis in CNS. However, the level of P2Y6R in Parkinson’s disease (PD patients is unclear. Therefore, we measured the level of P2Y6R in PD patients and speculated whether it could be a potential biomarker for PD. Given on the basis that P2Y6R was higher in PD patients, we further explored the mechanisms underlying P2Y6R in the pathogenesis of PD. Methods We tested the expression level of P2Y6R in the peripheral blood mononuclear cells (PBMCs among 145 PD patients, 170 healthy controls, and 30 multiple system atrophy (MSA patients. We also used a lipopolysaccharide (LPS-stimulated microglial cell culture model to investigate (i the effects of LPS on P2Y6R expression with western blot and RT-PCR, (ii the effects of LPS on UDP expression using HPLC, (iii the effects of UDP/P2Y6R signaling on cytokine expression using western blot, RT-PCR, and ELISA, and (iv the signaling pathways activated by the P2Y6R involved in the neuroinflammation. Results Expression levels of P2Y6R in PD patients were higher than healthy controls and MSA patients. P2Y6R could be a good biomarker of PD. P2Y6R was also upregulated in LPS-treated BV-2 cells and involved in proinflammatory cytokine release through an autocrine loop based on LPS-triggered UDP secretion and accelerated neuroinflammatory responses through the ERK1/2 pathway. Importantly, blocking UDP/P2Y6R signaling could reverse these pathological processes. Conclusions P2Y6R may be a potential clinical biomarker of PD. Blocking P2Y6R may be a potential therapeutic approach to the treatment of PD patients through inhibition of microglia-activated neuroinflammation.

  9. Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor

    Science.gov (United States)

    Leiva-Salcedo, Elias; Coddou, Claudio; Rodríguez, Felipe E.; Penna, Antonello; Lopez, Ximena; Neira, Tanya; Fernández, Ricardo; Imarai, Mónica; Rios, Miguel; Escobar, Jorge; Montoya, Margarita; Huidobro-Toro, J. Pablo; Escobar, Alejandro; Acuña-Castillo, Claudio

    2011-01-01

    The purinergic P2X7 receptor (P2X7R) plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS) is one of the strongest stimuli of the immune response, and it has been shown that P2X7R activation can modulate LPS-induced responses. Moreover, a C-terminal binding site for LPS has been proposed. In order to evaluate if LPS can directly modulate the activity of the P2X7R, we tested several signaling pathways associated with P2X7R activation in HEK293 cells that do not express the TLR-4 receptor. We found that LPS alone was unable to induce any P2X7R-related activity, suggesting that the P2X7R is not directly activated by the endotoxin. On the other hand, preapplication of LPS inhibited ATP-induced currents, intracellular calcium increase, and ethidium bromide uptake and had no effect on ERK activation in HEK293 cells. In splenocytes-derived T-regulatory cells, in which ATP-induced apoptosis is driven by the P2X7R, LPS inhibited ATP-induced apoptosis. Altogether, these results demonstrate that LPS modulates the activity of the P2X7R and suggest that this effect could be of physiological relevance. PMID:21941410

  10. Tungsten phosphanylarylthiolato complexes [W{PhP(2-SC6H4)2-kappa3S,S',P} 2] and [W{P(2-SC6H4)3-kappa4S,S',S",P}2]: synthesis, structures and redox chemistry.

    Science.gov (United States)

    Hildebrand, Alexandra; Lönnecke, Peter; Silaghi-Dumitrescu, Luminita; Hey-Hawkins, Evamarie

    2008-09-14

    PhP(2-SHC6H4)2 (PS2H2) reacts with WCl6 with reduction of tungsten to give the air-sensitive tungsten(IV) complex [W{PhP(2-SC6H4)2-kappa(3)S,S',P}2] (1). 1 is oxidised in air to [WO{PhPO(2-SC6H4)2-kappa(3)S,S',O}{PhP(2-SC6H4)2-kappa(3)S,S',P}] (2). The attempted synthesis of 2 by reaction of 1 with iodosobenzene as oxidising agent was unsuccessful. [W{P(2-SC6H4)3-kappa(4)S,S',S",P}2] (3) was formed in the reaction of P(2-SHC6H4)3 (PS3H3) with WCl6. The W(VI) complex 3 contains two PS3(3-) ligands, each coordinated in a tetradentate fashion resulting in a tungsten coordination number of eight. The reaction of 3 with AgBF4 yields the dinuclear tungsten complex [W2{P(2-SC6H4)3-kappa(4)S,S',S",P}3]BF4 (4). Complexes 1-4 were characterised by spectral methods and X-ray structure determination.

  11. Cell type-specific expression of FoxP2 in the ferret and mouse retina.

    Science.gov (United States)

    Sato, Chihiro; Iwai-Takekoshi, Lena; Ichikawa, Yoshie; Kawasaki, Hiroshi

    2017-04-01

    Although the anatomical and physiological properties of subtypes of retinal ganglion cells (RGCs) have been extensively investigated, their molecular properties are still unclear. Here, we examined the expression patterns of FoxP2 in the retina of ferrets and mice. We found that FoxP2 was expressed in small subsets of neurons in the adult ferret retina. FoxP2-positive neurons in the ganglion cell layer were divided into two groups. Large FoxP2-positive neurons expressed Brn3a and were retrogradely labeled with cholera toxin subunit B injected into the optic nerve, indicating that they are RGCs. The soma size and the projection pattern of FoxP2-positive RGCs were consistent with those of X cells. Because we previously reported that FoxP2 was selectively expressed in X cells in the ferret lateral geniculate nucleus (LGN), our findings indicate that FoxP2 is specifically expressed in the parvocellular pathway from the retina to the LGN. Small FoxP2-positive neurons were positive for GAD65/67, suggesting that they are GABAergic amacrine cells. Most Foxp2-positive cells were RGCs in the adult mouse retina. Dendritic morphological analyses suggested that Foxp2-positive RGCs included direction-selective RGCs in mice. Thus, our findings suggest that FoxP2 is expressed in specific subtypes of RGCs in the retina of ferrets and mice. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  12. Transformation of Astrocytes to a Neuroprotective Phenotype by Microglia via P2Y1 Receptor Downregulation

    Directory of Open Access Journals (Sweden)

    Youichi Shinozaki

    2017-05-01

    Full Text Available Microglia and astrocytes become reactive following traumatic brain injury (TBI. However, the coordination of this reactivity and its relation to pathophysiology are unclear. Here, we show that microglia transform astrocytes into a neuroprotective phenotype via downregulation of the P2Y1 purinergic receptor. TBI initially caused microglial activation in the injury core, followed by reactive astrogliosis in the peri-injured region and formation of a neuroprotective astrocyte scar. Equivalent changes to astrocytes were observed in vitro after injury. This change in astrocyte phenotype resulted from P2Y1 receptor downregulation, mediated by microglia-derived cytokines. In mice, astrocyte-specific P2Y1 receptor overexpression (Astro-P2Y1OE counteracted scar formation, while astrocyte-specific P2Y1 receptor knockdown (Astro-P2Y1KD facilitated scar formation, suggesting critical roles of P2Y1 receptors in the transformation. Astro-P2Y1OE and Astro-P2Y1KD mice showed increased and reduced neuronal damage, respectively. Altogether, our findings indicate that microglia-astrocyte interaction, involving a purinergic signal, is essential for the formation of neuroprotective astrocytes.

  13. Accelerated tumor progression in mice lacking the ATP receptor P2X7

    DEFF Research Database (Denmark)

    Adinolfi, Elena; Capece, Marina; Franceschini, Alessia

    2015-01-01

    The ATP receptor P2X7 (P2X7R or P2RX7) has a key role in inflammation and immunity, but its possible roles in cancer are not firmly established. In the present study, we investigated the effect of host genetic deletion of P2X7R in the mouse on the growth of B16 melanoma or CT26 colon carcinoma...... IL-1β and VEGF release were drastically reduced, and inflammatory cell infiltration was abrogated nearly completely. Similarly, tumor growth was also greatly accelerated in wt chimeric mice implanted with P2X7R-deficient bone marrow cells, defining hematopoietic cells as a sufficient site of P2X7R...... action. Finally, dendritic cells from P2X7R-deficient mice were unresponsive to stimulation with tumor cells, and chemotaxis of P2X7R-less cells was impaired. Overall, our results showed that host P2X7R expression was critical to support an antitumor immune response, and to restrict tumor growth...

  14. Non-nucleotide Agonists Triggering P2X7 Receptor Activation and Pore Formation

    OpenAIRE

    Francesco Di Virgilio; Anna L. Giuliani; Valentina Vultaggio-Poma; Simonetta Falzoni; Alba C. Sarti

    2018-01-01

    The P2X7 receptor (P2X7R) is a ligand-gated plasma membrane ion channel belonging to the P2X receptor subfamily activated by extracellular nucleotides. General consensus holds that the physiological (and maybe the only) agonist is ATP. However, scattered evidence generated over the last several years suggests that ATP might not be the only agonist, especially at inflammatory sites. Solid data show that NAD+ covalently modifies the P2X7R of mouse T lymphocytes, thus lowering the ATP threshold ...

  15. Purinergic P2X7 receptor regulates lung surfactant secretion in a paracrine manner

    Science.gov (United States)

    Mishra, Amarjit; Chintagari, Narendranath Reddy; Guo, Yujie; Weng, Tingting; Su, Lijing; Liu, Lin

    2011-01-01

    Alveolar epithelium is composed of alveolar epithelial cells of type I (AEC I) and type II (AEC II). AEC II secrete lung surfactant by means of exocytosis. P2X7 receptor (P2X7R), a P2 purinergic receptor, has been implicated in the regulation of synaptic transmission and inflammation. Here, we report that P2X7R, which is expressed in AEC I but not AEC II, is a novel mediator for the paracrine regulation of surfactant secretion in AEC II. In primary co-cultures of AEC I and AEC II benzoyl ATP (BzATP; an agonist of P2X7R) increased surfactant secretion, which was blocked by the P2X7R antagonist Brilliant Blue G. This effect was observed in AEC II co-cultured with human embryonic kidney HEK-293 cells stably expressing rat P2X7R, but not when co-cultured with AEC I in which P2X7R was knocked down or in co-cultures of AEC I and AEC II isolated from P2X7R−/− mice. BzATP-mediated secretion involved P2Y2 receptor signaling because it was reduced by the addition of the ATP scavengers apyrase and adenosine deaminase and the P2Y2 receptor antagonist suramin. However, the stimulation with BzATP might also release other substances that potentially increase surfactant secretion as a greater stimulation of secretion was observed in AEC II incubated with BzATP when co-cultured with E10 or HEK-293-P2X7R cells than with ATP alone. P2X7R−/− mice failed to increase surfactant secretion in response to hyperventilation, pointing to the physiological relevance of P2X7R in maintaining surfactant homeostasis in the lung. These results suggest that the activation of P2X7R increases surfactant secretion by releasing ATP from AEC I and subsequently stimulating P2Y2 receptors in AEC II. PMID:21266468

  16. Transformation of Astrocytes to a Neuroprotective Phenotype by Microglia via P2Y1Receptor Downregulation.

    Science.gov (United States)

    Shinozaki, Youichi; Shibata, Keisuke; Yoshida, Keitaro; Shigetomi, Eiji; Gachet, Christian; Ikenaka, Kazuhiro; Tanaka, Kenji F; Koizumi, Schuichi

    2017-05-09

    Microglia and astrocytes become reactive following traumatic brain injury (TBI). However, the coordination of this reactivity and its relation to pathophysiology are unclear. Here, we show that microglia transform astrocytes into a neuroprotective phenotype via downregulation of the P2Y 1 purinergic receptor. TBI initially caused microglial activation in the injury core, followed by reactive astrogliosis in the peri-injured region and formation of a neuroprotective astrocyte scar. Equivalent changes to astrocytes were observed in vitro after injury. This change in astrocyte phenotype resulted from P2Y 1 receptor downregulation, mediated by microglia-derived cytokines. In mice, astrocyte-specific P2Y 1 receptor overexpression (Astro-P2Y 1 OE) counteracted scar formation, while astrocyte-specific P2Y 1 receptor knockdown (Astro-P2Y 1 KD) facilitated scar formation, suggesting critical roles of P2Y 1 receptors in the transformation. Astro-P2Y 1 OE and Astro-P2Y 1 KD mice showed increased and reduced neuronal damage, respectively. Altogether, our findings indicate that microglia-astrocyte interaction, involving a purinergic signal, is essential for the formation of neuroprotective astrocytes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Computer technologies for industrial risk prevention and emergency management; Tecnologie informatiche per la prevenzione dei rischi industriali e la gestione delle emergenze

    Energy Technology Data Exchange (ETDEWEB)

    Balducelli, C.; Bologna, S.; Di Costanzo, G.; Vicoli, G. [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dip. Energia

    1996-07-01

    This document provides an overview about problems related to the engineering of computer based systems for industrial risk prevention and emergency management. Such systems are rather complex and subject to precise reliability and safety requirements. With the evolution of information technologies, such systems are becoming to be the means for building protective barriers for reduction of risk associated with plant operations. For giving more generality to this document, and for not concentrating on only a specific plant, the emergency management systems will be dealt with more details than ones for accident prevention. The document is organized in six chapters. Chapter one is an introduction to the problem and to its state of art, with particular emphasis to the aspects of safety requirements definition. Chapter two is an introduction to the problems related to the emergency management and to the training of operators in charge of this task. Chapter three deals in details the topic of the Training Support Systems, in particular about MUSTER (multi-user system for training and evaluation of environmental emergency response) system. Chapter four deals in details the topic of decision support systems, in particular about ISEM (information technology support for emergency management) system. Chapter five illustrates an application of support to the operators of Civil Protection Department for the management of emergencies in the fields of industrial chemical. Chapter six is about a synthesis of the state of art and the future possibilities, identifying some research and development activities more promising for the future.

  18. Protecting the health of the @hlete: how online technology may aid our common goal to prevent injury and illness in sport.

    Science.gov (United States)

    Verhagen, Evert; Bolling, Caroline

    2015-09-01

    Online technology dominates our era and eHealth has become a reality for sports clinicians and researchers. Contemporary online platforms enable self-monitoring and provide tailored feedback to the different stakeholders who play a role in the health and care of athletes. Innovations such as digital monitoring, mobile applications and connected hardware provide the critical tools to solve current enigmas in sports medicine research, and to streamline and facilitate injury prevention, management and rehabilitation. eHealth is not an emerging future of sports medicine-the technology to move our field forward in terms of research and practice is already available. This Analysis is based on Evert Verhagen's keynote presentation at the IOC World Conference on Injury and Illness Prevention in Sport (Monaco, 12 April 2014). It outlines the use of eHealth in research, implementation and practice, and provides an overview of possibilities and opportunities that existing and emerging eHealth solutions provide for sports and exercise medicine and physiotherapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. Intricacies and strategies for the implementation of new technologies in radiotherapy: Reflections on the meaning and prevention of the error

    Energy Technology Data Exchange (ETDEWEB)

    Espejo-Villalobos, J. D.; Franco-Cabrera, M. C.; Estrada-Hernandez, C.; Quintero-Castelan, M. S. [Centro Medico Hospital San Jose -TEC Salud, Department of Radiothrapy. Av. Ignacio Morones Prieto 3000 Pte. Col. Los Doctores, Monterrey, Nuevo Leon, 64710 (Mexico)

    2012-10-23

    When facing the challenge of implementing new technologies in Radiotherapy, a reflection on philosophical and ethical principles is in order for the Medical Physicist to assume a reality of increased risks of harm to the patient. A series of ideas from philosophers and clinical professionals are reviewed to encourage an increased awareness of our ethical responsibility towards patients that entrust us with their hopes for alleviating their disease.

  20. Intricacies and strategies for the implementation of new technologies in radiotherapy: Reflections on the meaning and prevention of the error

    International Nuclear Information System (INIS)

    Espejo-Villalobos, J. D.; Franco-Cabrera, M. C.; Estrada-Hernandez, C.; Quintero-Castelan, M. S.

    2012-01-01

    When facing the challenge of implementing new technologies in Radiotherapy, a reflection on philosophical and ethical principles is in order for the Medical Physicist to assume a reality of increased risks of harm to the patient. A series of ideas from philosophers and clinical professionals are reviewed to encourage an increased awareness of our ethical responsibility towards patients that entrust us with their hopes for alleviating their disease.

  1. Colchicine inhibits cationic dye uptake induced by ATP in P2X2 and P2X7 receptor-expressing cells: implications for its therapeutic action

    Science.gov (United States)

    Marques-da-Silva, C; Chaves, MM; Castro, NG; Coutinho-Silva, R; Guimaraes, MZP

    2011-01-01

    BACKGROUND AND PURPOSE The two longest C-termini of the purinergic P2X receptors occur in the P2X2 and P2X7 receptors and are thought to interact with multiple cytoplasmic proteins, among which are members of the cytoskeleton, including microtubules. In this work we asked whether disrupting the microtubule cytoskeleton might affect the functions of these receptors. EXPERIMENTAL APPROACH Functions of heterologously expressed P2X2 and P2X7 receptors were evaluated with electrophysiology and dye uptake following ATP application. Permeabilization and secretion of pro-inflammatory agents were quantified from fresh or cultured peritoneal mouse macrophages, treated in vitro or in vivo with colchicine. KEY RESULTS Disrupting the microtubule network with colchicine did not affect currents generated by ATP in P2X2 and P2X7 receptor-expressing cells but inhibited uptake of the dye Yo-Pro-1 in Xenopus oocytes and HEK293 cells expressing these channels. Peritoneal mouse macrophages showed less ATP-induced permeabilization to ethidium bromide in the presence of colchicine, and less reactive oxygen species (ROS) formation, nitric oxide (NO) and interleukin (IL)-1β release. Colchicine treatment did not affect ATP-evoked currents in macrophages. Finally, in vivo assays with mice inoculated with lipopolysaccharide and ATP showed diminished ROS, IL-1β, interferon-γ and NO production after colchicine treatment. CONCLUSIONS AND IMPLICATIONS Colchicine has known anti-inflammatory actions and is used to treat several conditions involving innate immunity, including gout and familial Mediterranean fever. Here we propose a new mechanism of action – inhibition of pore formation induced by activation of P2X receptors – which could explain some of the anti-inflammatory effects of colchicine. LINKED ARTICLE This article is commented on by Pelegrín, pp. 908–911 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01325.x PMID:21306580

  2. Evaluation and refinement of a handheld health information technology tool to support the timely update of bedside visual cues to prevent falls in hospitals.

    Science.gov (United States)

    Teh, Ruth C-A; Visvanathan, Renuka; Ranasinghe, Damith; Wilson, Anne

    2017-11-27

    To evaluate clinicians' perspectives, before and after clinical implementation (i.e. trial) of a handheld health information technology (HIT) tool, incorporating an iPad device and automatically generated visual cues for bedside display, for falls risk assessment and prevention in hospital. This pilot study utilized mixed-methods research with focus group discussions and Likert-scale surveys to elicit clinicians' attitudes. The study was conducted across three phases within two medical wards of the Queen Elizabeth Hospital. Phase 1 (pretrial) involved focus group discussion (five staff) and surveys (48 staff) to elicit preliminary perspectives on tool use, benefits and barriers to use and recommendations for improvement. Phase 2 (tool trial) involved HIT tool implementation on two hospital wards over consecutive 12-week periods. Phase 3 (post-trial) involved focus group discussion (five staff) and surveys (29 staff) following tool implementation, with similar themes as in Phase 1. Qualitative data were evaluated using content analysis, and quantitative data using descriptive statistics and logistic regression analysis, with subgroup analyses on user status (P ≤ 0.05). Four findings emerged on clinicians' experience, positive perceptions, negative perceptions and recommendations for improvement of the tool. Pretrial, clinicians were familiar with using visual cues in hospital falls prevention. They identified potential benefits of the HIT tool in obtaining timely, useful falls risk assessment to improve patient care. During the trial, the wards differed in methods of tool implementation, resulting in lower uptake by clinicians on the subacute ward. Post-trial, clinicians remained supportive for incorporating the tool into clinical practice; however, there were issues with usability and lack of time for tool use. Staff who had not used the tool had less appreciation for it improving their understanding of patients' falls risk factors (odds ratio 0.12), or

  3. Use of a Business Approach to Improve Disease Surveillance Data Management Systems and Information Technology Process in Florida's Bureau of STD Prevention and Control.

    Science.gov (United States)

    Shiver, Stacy A; Schmitt, Karla; Cooksey, Adrian

    2009-01-01

    The business of sexually transmitted disease (STD) prevention and control demands technology that is capable of supporting a wide array of program activities-from the processing of laboratory test results to the complex and confidential process involved in contact investigation. The need for a tool that enables public health officials to successfully manage the complex operations encountered in an STD prevention and control program, and the need to operate in an increasingly poor resource environment, led the Florida Bureau of STD to develop the Patient Reporting Investigation Surveillance Manager. Its unique approach, technical architecture, and sociotechnical philosophy have made this business application successful in real-time monitoring of disease burden for local communities, identification of emerging outbreaks, monitoring and assurance of appropriate treatments, improving access to laboratory data, and improving the quality of data for epidemiologic analysis. Additionally, the effort attempted to create and release a product that promoted the Centers for Disease Control and Prevention's ideas for integration of programs and processes.

  4. Analysis of Qualitative Interviews about the Impact of Information Technology on Pressure Ulcer Prevention Programs: Implications for the Wound Ostomy Continence Nurse

    Science.gov (United States)

    Shepherd, Marilyn Murphy; Wipke-Tevis, Deidre D.; Alexander, Gregory L.

    2015-01-01

    Purpose The purpose of this study was to compare pressure ulcer prevention programs in 2 long term care facilities (LTC) with diverse Information Technology Sophistication (ITS), one with high sophistication and one with low sophistication, and to identify implications for the Wound Ostomy Continence Nurse (WOC Nurse) Design Secondary analysis of narrative data obtained from a mixed methods study. Subjects and Setting The study setting was 2 LTC facilities in the Midwestern United States. The sample comprised 39 staff from 2 facilities, including 26 from a high ITS facility and 13 from the low ITS facility. Respondents included Certified Nurse Assistants,, Certified Medical Technicians, Restorative Medical Technicians, Social Workers, Registered Nurses, Licensed Practical Nurses, Information Technology staff, Administrators, and Directors. Methods This study is a secondary analysis of interviews regarding communication and education strategies in two longterm care agencies. This analysis focused on focus group interviews, which included both direct and non-direct care providers. Results Eight themes (codes) were identified in the analysis. Three themes are presented individually with exemplars of communication and education strategies. The analysis revealed specific differences between the high ITS and low ITS facility in regards to education and communication involving pressure ulcer prevention. These differences have direct implications for WOC nurses consulting in the LTC setting. Conclusions Findings from this study suggest that effective strategies for staff education and communication regarding PU prevention differ based on the level of ITS within a given facility. Specific strategies for education and communication are suggested for agencies with high ITS and agencies with low ITS sophistication. PMID:25945822

  5. Adherence to self-monitoring via interactive voice response technology in an eHealth intervention targeting weight gain prevention among Black women: randomized controlled trial.

    Science.gov (United States)

    Steinberg, Dori M; Levine, Erica L; Lane, Ilana; Askew, Sandy; Foley, Perry B; Puleo, Elaine; Bennett, Gary G

    2014-04-29

    eHealth interventions are effective for weight control and have the potential for broad reach. Little is known about the use of interactive voice response (IVR) technology for self-monitoring in weight control interventions, particularly among populations disproportionately affected by obesity. This analysis sought to examine patterns and predictors of IVR self-monitoring adherence and the association between adherence and weight change among low-income black women enrolled in a weight gain prevention intervention. The Shape Program was a randomized controlled trial comparing a 12-month eHealth behavioral weight gain prevention intervention to usual care among overweight and obese black women in the primary care setting. Intervention participants (n=91) used IVR technology to self-monitor behavior change goals (eg, no sugary drinks, 10,000 steps per day) via weekly IVR calls. Weight data were collected in clinic at baseline, 6, and 12 months. Self-monitoring data was stored in a study database and adherence was operationalized as the percent of weeks with a successful IVR call. Over 12 months, the average IVR completion rate was 71.6% (SD 28.1) and 52% (47/91) had an IVR completion rate ≥80%. At 12 months, IVR call completion was significantly correlated with weight loss (r =-.22; P=.04) and participants with an IVR completion rate ≥80% had significantly greater weight loss compared to those with an IVR completion rate self-monitoring. Adherence to IVR self-monitoring was high among socioeconomically disadvantaged black women enrolled in a weight gain prevention intervention. Higher adherence to IVR self-monitoring was also associated with greater weight change. IVR is an effective and useful tool to promote self-monitoring and has the potential for widespread use and long-term sustainability. Clinicaltrials.gov NCT00938535; http://www.clinicaltrials.gov/ct2/show/NCT00938535.

  6. Identification and characterization of a selective allosteric antagonist of human P2X4 receptor channels.

    Science.gov (United States)

    Ase, Ariel R; Honson, Nicolette S; Zaghdane, Helmi; Pfeifer, Tom A; Séguéla, Philippe

    2015-04-01

    P2X4 is an ATP-gated nonselective cation channel highly permeable to calcium. There is increasing evidence that this homomeric purinoceptor, which is expressed in several neuronal and immune cell types, is involved in chronic pain and inflammation. The current paucity of unambiguous pharmacological tools available to interrogate or modulate P2X4 function led us to pursue the search for selective antagonists. In the high-throughput screen of a compound library, we identified the phenylurea BX430 (1-(2,6-dibromo-4-isopropyl-phenyl)-3-(3-pyridyl)urea, molecular weight = 413), with antagonist properties on human P2X4-mediated calcium uptake. Patch-clamp electrophysiology confirmed direct inhibition of P2X4 currents by extracellular BX430, with submicromolar potency (IC50 = 0.54 µM). BX430 is highly selective, having virtually no functional impact on all other P2X subtypes, namely, P2X1-P2X3, P2X5, and P2X7, at 10-100 times its IC50. Unexpected species differences were noticed, as BX430 is a potent antagonist of zebrafish P2X4 but has no effect on rat and mouse P2X4 orthologs. The concentration-response curve for ATP on human P2X4 in the presence of BX430 shows an insurmountable blockade, indicating a noncompetitive allosteric mechanism of action. Using a fluorescent dye uptake assay, we observed that BX430 also effectively suppresses ATP-evoked and ivermectin-potentiated membrane permeabilization induced by P2X4 pore dilation. Finally, in single-cell calcium imaging, we validated its selective inhibitory effects on native P2X4 channels at the surface of human THP-1 cells that were differentiated into macrophages. In summary, this ligand provides a novel molecular probe to assess the specific role of P2X4 in inflammatory and neuropathic conditions, where ATP signaling has been shown to be dysfunctional. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  7. Immunocytochemical analysis of P2X2 in rat circumvallate taste buds

    Directory of Open Access Journals (Sweden)

    Yang Ruibiao

    2012-05-01

    Full Text Available Abstract Background Our laboratory has shown that classical synapses and synaptic proteins are associated with Type III cells. Yet it is generally accepted that Type II cells transduce bitter, sweet and umami stimuli. No classical synapses, however, have been found associated with Type II cells. Recent studies indicate that the ionotropic purinergic receptors P2X2/P2X3 are present in rodent taste buds. Taste nerve processes express the ionotropic purinergic receptors (P2X2/P2X3. P2X2/P2X3Dbl−/− mice are not responsive to sweet, umami and bitter stimuli, and it has been proposed that ATP acts as a neurotransmitter in taste buds. The goal of the present study is to learn more about the nature of purinergic contacts in rat circumvallate taste buds by examining immunoreactivity to antisera directed against the purinergic receptor P2X2. Results P2X2-like immunoreactivity is present in intragemmal nerve processes in rat circumvallate taste buds. Intense immunoreactivity can also be seen in the subgemmal nerve plexuses located below the basal lamina. The P2X2 immunoreactive nerve processes also display syntaxin-1-LIR. The immunoreactive nerves are in close contact with the IP3R3-LIR Type II cells and syntaxin-1-LIR and/or 5-HT-LIR Type III cells. Taste cell synapses are observed only from Type III taste cells onto P2X2-LIR nerve processes. Unusually large, “atypical” mitochondria in the Type II taste cells are found only at close appositions with P2X2-LIR nerve processes. P2X2 immunogold particles are concentrated at the membranes of nerve processes at close appositions with taste cells. Conclusions Based on our immunofluorescence and immunoelectron microscopical studies we believe that both perigemmal and most all intragemmal nerve processes display P2X2-LIR. Moreover, colloidal gold immunoelectron microscopy indicates that P2X2-LIR in nerve processes is concentrated at sites of close apposition with Type II cells. This supports the hypothesis

  8. Non-nucleotide Agonists Triggering P2X7 Receptor Activation and Pore Formation

    Directory of Open Access Journals (Sweden)

    Francesco Di Virgilio

    2018-02-01

    Full Text Available The P2X7 receptor (P2X7R is a ligand-gated plasma membrane ion channel belonging to the P2X receptor subfamily activated by extracellular nucleotides. General consensus holds that the physiological (and maybe the only agonist is ATP. However, scattered evidence generated over the last several years suggests that ATP might not be the only agonist, especially at inflammatory sites. Solid data show that NAD+ covalently modifies the P2X7R of mouse T lymphocytes, thus lowering the ATP threshold for activation. Other structurally unrelated agents have been reported to activate the P2X7R via a poorly understood mechanism of action: (a the antibiotic polymyxin B, possibly a positive allosteric P2X7R modulator, (b the bactericidal peptide LL-37, (c the amyloidogenic β peptide, and (d serum amyloid A. Some agents, such as Alu-RNA, have been suggested to activate the P2X7R acting on the intracellular N- or C-terminal domains. Mode of P2X7R activation by these non-nucleotide ligands is as yet unknown; however, these observations raise the intriguing question of how these different non-nucleotide ligands may co-operate with ATP at inflammatory or tumor sites. New information obtained from the cloning and characterization of the P2X7R from exotic mammalian species (e.g., giant panda and data from recent patch-clamp studies are strongly accelerating our understanding of P2X7R mode of operation, and may provide hints to the mechanism of activation of P2X7R by non-nucleotide ligands.

  9. Long-term heart transplant survival by targeting the ionotropic purinergic receptor P2X7.

    Science.gov (United States)

    Vergani, Andrea; Tezza, Sara; D'Addio, Francesca; Fotino, Carmen; Liu, Kaifeng; Niewczas, Monika; Bassi, Roberto; Molano, R Damaris; Kleffel, Sonja; Petrelli, Alessandra; Soleti, Antonio; Ammirati, Enrico; Frigerio, Maria; Visner, Gary; Grassi, Fabio; Ferrero, Maria E; Corradi, Domenico; Abdi, Reza; Ricordi, Camillo; Sayegh, Mohamed H; Pileggi, Antonello; Fiorina, Paolo

    2013-01-29

    Heart transplantation is a lifesaving procedure for patients with end-stage heart failure. Despite much effort and advances in the field, current immunosuppressive regimens are still associated with poor long-term cardiac allograft outcomes, and with the development of complications, including infections and malignancies, as well. The development of a novel, short-term, and effective immunomodulatory protocol will thus be an important achievement. The purine ATP, released during cell damage/activation, is sensed by the ionotropic purinergic receptor P2X7 (P2X7R) on lymphocytes and regulates T-cell activation. Novel clinical-grade P2X7R inhibitors are available, rendering the targeting of P2X7R a potential therapy in cardiac transplantation. We analyzed P2X7R expression in patients and mice and P2X7R targeting in murine recipients in the context of cardiac transplantation. Our data demonstrate that P2X7R is specifically upregulated in graft-infiltrating lymphocytes in cardiac-transplanted humans and mice. Short-term P2X7R targeting with periodate-oxidized ATP promotes long-term cardiac transplant survival in 80% of murine recipients of a fully mismatched allograft. Long-term survival of cardiac transplants was associated with reduced T-cell activation, T-helper cell 1/T-helper cell 17 differentiation, and inhibition of STAT3 phosphorylation in T cells, thus leading to a reduced transplant infiltrate and coronaropathy. In vitro genetic upregulation of the P2X7R pathway was also shown to stimulate T-helper cell 1/T-helper cell 17 cell generation. Finally, P2X7R targeting halted the progression of coronaropathy in a murine model of chronic rejection as well. P2X7R targeting is a novel clinically relevant strategy to prolong cardiac transplant survival.

  10. Modulation of P2X7 Receptor during Inflammation in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Susanna Amadio

    2017-11-01

    Full Text Available Multiple sclerosis (MS is characterized by macrophage accumulation and inflammatory infiltrates into the CNS contributing to demyelination. Because purinergic P2X7 receptor (P2X7R is known to be abundantly expressed on cells of the hematopoietic lineage and of the nervous system, we further investigated its phenotypic expression in MS and experimental autoimmune encephalomyelitis conditions. By quantitative reverse transcription polymerase chain reaction and flow cytometry, we analyzed the P2X7R expression in human mononuclear cells of peripheral blood from stable and acute relapsing-remitting MS phases. Human monocytes were also challenged in vitro with pro-inflammatory stimuli such as the lipopolysaccharide, or the P2X7R preferential agonist 2′(3′-O-(4 Benzoylbenzoyladenosine 5′-triphosphate, before evaluating P2X7R protein expression. Finally, by immunohistochemistry and immunofluorescence confocal analysis, we investigated the P2X7R expression in frontal cortex from secondary progressive MS cases. We demonstrated that P2X7R is present and inhibited on peripheral monocytes isolated from MS donors during the acute phase of the disease, moreover it is down-regulated in human monocytes after pro-inflammatory stimulation in vitro. P2X7R is instead up-regulated on astrocytes in the parenchyma of frontal cortex from secondary progressive MS patients, concomitantly with monocyte chemoattractant protein-1 chemokine, while totally absent from microglia/macrophages or oligodendrocytes, despite the occurrence of inflammatory conditions. Our results suggest that inhibition of P2X7R on monocytes and up-regulation in astrocytes might contribute to sustain inflammatory mechanisms in MS. By acquiring further knowledge about P2X7R dynamics and identifying P2X7R as a potential marker for the disease, we expect to gain insights into the molecular pathways of MS.

  11. Targeting of the P2X7 receptor in pancreatic cancer and stellate cells.

    Science.gov (United States)

    Giannuzzo, Andrea; Saccomano, Mara; Napp, Joanna; Ellegaard, Maria; Alves, Frauke; Novak, Ivana

    2016-12-01

    The ATP-gated receptor P2X7 (P2X7R) is involved in regulation of cell survival and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer and new markers and therapeutic targets are needed. PDAC is characterized by a complex tumour microenvironment, which includes cancer and pancreatic stellate cells (PSCs), and potentially high nucleotide/side turnover. Our aim was to determine P2X7R expression and function in human pancreatic cancer cells in vitro as well as to perform in vivo efficacy study applying P2X7R inhibitor in an orthotopic xenograft mouse model of PDAC. In the in vitro studies we show that human PDAC cells with luciferase gene (PancTu-1 Luc cells) express high levels of P2X7R protein. Allosteric P2X7R antagonist AZ10606120 inhibited cell proliferation in basal conditions, indicating that P2X7R was tonically active. Extracellular ATP and BzATP, to which the P2X7R is more sensitive, further affected cell survival and confirmed complex functionality of P2X7R. PancTu-1 Luc migration and invasion was reduced by AZ10606120, and it was stimulated by PSCs, but not by PSCs from P2X7(-/-) animals. PancTu-1 Luc cells were orthotopically transplanted into nude mice and tumour growth was followed noninvasively by bioluminescence imaging. AZ10606120-treated mice showed reduced bioluminescence compared to saline-treated mice. Immunohistochemical analysis confirmed P2X7R expression in cancer and PSC cells, and in metaplastic/neoplastic acinar and duct structures. PSCs number/activity and collagen deposition was reduced in AZ10606120-treated tumours. © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

  12. Non-nucleotide Agonists Triggering P2X7 Receptor Activation and Pore Formation.

    Science.gov (United States)

    Di Virgilio, Francesco; Giuliani, Anna L; Vultaggio-Poma, Valentina; Falzoni, Simonetta; Sarti, Alba C

    2018-01-01

    The P2X7 receptor (P2X7R) is a ligand-gated plasma membrane ion channel belonging to the P2X receptor subfamily activated by extracellular nucleotides. General consensus holds that the physiological (and maybe the only) agonist is ATP. However, scattered evidence generated over the last several years suggests that ATP might not be the only agonist, especially at inflammatory sites. Solid data show that NAD + covalently modifies the P2X7R of mouse T lymphocytes, thus lowering the ATP threshold for activation. Other structurally unrelated agents have been reported to activate the P2X7R via a poorly understood mechanism of action: (a) the antibiotic polymyxin B, possibly a positive allosteric P2X7R modulator, (b) the bactericidal peptide LL-37, (c) the amyloidogenic β peptide, and (d) serum amyloid A. Some agents, such as Alu-RNA, have been suggested to activate the P2X7R acting on the intracellular N- or C-terminal domains. Mode of P2X7R activation by these non-nucleotide ligands is as yet unknown; however, these observations raise the intriguing question of how these different non-nucleotide ligands may co-operate with ATP at inflammatory or tumor sites. New information obtained from the cloning and characterization of the P2X7R from exotic mammalian species (e.g., giant panda) and data from recent patch-clamp studies are strongly accelerating our understanding of P2X7R mode of operation, and may provide hints to the mechanism of activation of P2X7R by non-nucleotide ligands.

  13. Modulation of P2X7 Receptor during Inflammation in Multiple Sclerosis.

    Science.gov (United States)

    Amadio, Susanna; Parisi, Chiara; Piras, Eleonora; Fabbrizio, Paola; Apolloni, Savina; Montilli, Cinzia; Luchetti, Sabina; Ruggieri, Serena; Gasperini, Claudio; Laghi-Pasini, Franco; Battistini, Luca; Volonté, Cinzia

    2017-01-01

    Multiple sclerosis (MS) is characterized by macrophage accumulation and inflammatory infiltrates into the CNS contributing to demyelination. Because purinergic P2X7 receptor (P2X7R) is known to be abundantly expressed on cells of the hematopoietic lineage and of the nervous system, we further investigated its phenotypic expression in MS and experimental autoimmune encephalomyelitis conditions. By quantitative reverse transcription polymerase chain reaction and flow cytometry, we analyzed the P2X7R expression in human mononuclear cells of peripheral blood from stable and acute relapsing-remitting MS phases. Human monocytes were also challenged in vitro with pro-inflammatory stimuli such as the lipopolysaccharide, or the P2X7R preferential agonist 2'(3')-O-(4 Benzoylbenzoyl)adenosine 5'-triphosphate, before evaluating P2X7R protein expression. Finally, by immunohistochemistry and immunofluorescence confocal analysis, we investigated the P2X7R expression in frontal cortex from secondary progressive MS cases. We demonstrated that P2X7R is present and inhibited on peripheral monocytes isolated from MS donors during the acute phase of the disease, moreover it is down-regulated in human monocytes after pro-inflammatory stimulation in vitro . P2X7R is instead up-regulated on astrocytes in the parenchyma of frontal cortex from secondary progressive MS patients, concomitantly with monocyte chemoattractant protein-1 chemokine, while totally absent from microglia/macrophages or oligodendrocytes, despite the occurrence of inflammatory conditions. Our results suggest that inhibition of P2X7R on monocytes and up-regulation in astrocytes might contribute to sustain inflammatory mechanisms in MS. By acquiring further knowledge about P2X7R dynamics and identifying P2X7R as a potential marker for the disease, we expect to gain insights into the molecular pathways of MS.

  14. P2X7R suppression promotes glioma growth through epidermal growth factor receptor signal pathway.

    Science.gov (United States)

    Fang, Jingqin; Chen, Xiao; Zhang, Letian; Chen, Jinhua; Liang, Yi; Li, Xue; Xiang, Jianbo; Wang, Lili; Guo, Guangkuo; Zhang, Bo; Zhang, Weiguo

    2013-06-01

    P2X7 receptor (P2X7R) has been shown to mediate an anticancer effect via apoptosis in different types of cancer. However, whether P2X7R exerts a promoting or suppressive effect on brain glioma is still a controversial issue and its underlying mechanism remains unknown. We showed here that P2X7R suppression exerted a pro-growth effect on glioma through directly promoting cells proliferation and pro-angiogenesis, which was associated with epidermal growth factor receptor (EGFR) signaling. The P2X7R was markedly downregulated by cells exposure to the P2X7R antagonist, brilliant blue G (BBG), moreover, the cells proliferation was enhanced in a dose-dependent manner and the expression of EGFR or p-EGFR protein was significantly upregulated. By constructing C6 cells with reduced expression of P2X7R using shRNA, we also demonstrated strong upregulation in cells proliferation and EGFR/p-EGFR expression. However, this effect of BBG was reversed in the presence of gefitinib or suramin. Magnetic resonance imaging and computed tomography perfusion showed that the BBG or P2X7R shRNA promoted the tumor growth by about 40% and 50%, respectively, and significantly increased angiogenesis. Nissl and Ki-67 staining also confirmed that BBG or P2X7R shRNA notably increased the tumor growth. More importantly, either BBG or P2X7R shRNA could markedly upregulated the expression of EGFR, p-EGFR, HIF-1α and VEGF in glioma cells. In conclusion, P2X7R suppression exerts a promoting effect on glioma growth, which is likely to be related to upregulated EGFR, HIF-1α and VEGF expression. These findings provide important clues to the molecular basis of anticancer effect of targeting purinergic receptors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Gamma ray shielding and structural properties of PbO-P2O5-Na2WO4 glass system

    Science.gov (United States)

    Dogra, Mridula; Singh, K. J.; Kaur, Kulwinder; Anand, Vikas; Kaur, Parminder

    2017-05-01

    The present work has been undertaken to study the gamma ray shielding properties of PbO-P2O5-Na2WO4 glass system. The values of mass attenuation coefficient and half value layer parameter at photon energies 511, 662 and 1173 KeV have been determined using XCOM computer software developed by National Institute of Standards and Technology. The density, molar volume, XRD, UV-VIS and Raman studies have been performed to study the structural properties of the prepared glass system to check the possibility of the use of prepared samples as an alternate to conventional concrete for gamma ray shielding applications.

  16. Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P2 levels.

    Science.gov (United States)

    Dai, Gucan; Yu, Haijie; Kruse, Martin; Traynor-Kaplan, Alexis; Hille, Bertil

    2016-06-07

    Myo-inositol is an important cellular osmolyte in autoregulation of cell volume and fluid balance, particularly for mammalian brain and kidney cells. We find it also regulates excitability. Myo-inositol is the precursor of phosphoinositides, key signaling lipids including phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. However, whether myo-inositol accumulation during osmoregulation affects signaling and excitability has not been fully explored. We found that overexpression of the Na(+)/myo-inositol cotransporter (SMIT1) and myo-inositol supplementation enlarged intracellular PI(4,5)P2 pools, modulated several PI(4,5)P2-dependent ion channels including KCNQ2/3 channels, and attenuated the action potential firing of superior cervical ganglion neurons. Further experiments using the rapamycin-recruitable phosphatase Sac1 to hydrolyze PI(4)P and the P4M probe to visualize PI(4)P suggested that PI(4)P levels increased after myo-inositol supplementation with SMIT1 expression. Elevated relative levels of PIP and PIP2 were directly confirmed using mass spectrometry. Inositol trisphosphate production and release of calcium from intracellular stores also were augmented after myo-inositol supplementation. Finally, we found that treatment with a hypertonic solution mimicked the effect we observed with SMIT1 overexpression, whereas silencing tonicity-responsive enhancer binding protein prevented these effects. These results show that ion channel function and cellular excitability are under regulation by several "physiological" manipulations that alter the PI(4,5)P2 setpoint. We demonstrate a previously unrecognized linkage between extracellular osmotic changes and the electrical properties of excitable cells.

  17. Physiological contribution of P2X receptors in postreceptoral signal processing in the mouse retina.

    Science.gov (United States)

    Ichinohe, Sho; Ishii, Toshiyuki; Takahashi, Hiroshi; Kaneda, Makoto

    2017-02-01

    ATP activates P2X receptors and acts as a neurotransmitter in the nervous system. We have previously reported that P2X receptors modulate the firing rate of retinal ganglion cells. Since many subtypes of P2X receptors are distributed in the mouse retina, it is likely that the modulatory effects of P2X receptor-mediated signaling can occur at multiple synaptic levels in the retina. In this study, we investigated whether P2X receptors expressed between the photoreceptor layer and the inner nuclear layer in the mouse retina were physiologically functional, by electroretinography (ERG). In the combined rod-cone ERG and the scotopic ERG, intravitreal injection of PPADS, an antagonist of P2X receptors, had no effects on the amplitude of the a-wave, but decreased the amplitude of the b-wave. In the photopic ERG, intravitreal injection of PPADS significantly decreased the amplitude of both the a-wave and the b-wave. In ex vivo recordings, a decrease in the b-wave amplitude was observed at 20μM PPADS, confirming that the inhibition of the b-wave by intravitreal injection of PPADS is due to the inhibition of P2X receptors. Our findings suggest that P2X receptor-mediated signaling has a physiological effect in both the rod and the cone pathways in postreceptoral processing. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  18. On the non-existence of orthogonal instanton bundles on P^{2n+1}

    Directory of Open Access Journals (Sweden)

    Łucja Farnik

    2009-11-01

    Full Text Available In this paper we prove that there do not exist orthogonal instanton bundles on P^{2n+1} . In order to demonstrate this fact, we propose a new way of representing the invariant, introduced by L. Costa and G. Ottaviani, related to a rank 2n instanton bundle on P^{2n+1}.

  19. Evaluating Application-Layer Traffic Optimization Cost Metrics for P2P Multimedia Streaming

    DEFF Research Database (Denmark)

    Poderys, Justas; Soler, José

    2017-01-01

    To help users of P2P communication systems perform better-than-random selection of communication peers, Internet Engineering Task Force standardized the Application Layer Traffic Optimization (ALTO) protocol. The ALTO provided data-routing cost metric, can be used to rank peers in P2P communicati...

  20. PTEN Regulates PI(3,4)P2 Signaling Downstream of Class I PI3K.

    Science.gov (United States)

    Malek, Mouhannad; Kielkowska, Anna; Chessa, Tamara; Anderson, Karen E; Barneda, David; Pir, Pınar; Nakanishi, Hiroki; Eguchi, Satoshi; Koizumi, Atsushi; Sasaki, Junko; Juvin, Véronique; Kiselev, Vladimir Y; Niewczas, Izabella; Gray, Alexander; Valayer, Alexandre; Spensberger, Dominik; Imbert, Marine; Felisbino, Sergio; Habuchi, Tomonori; Beinke, Soren; Cosulich, Sabina; Le Novère, Nicolas; Sasaki, Takehiko; Clark, Jonathan; Hawkins, Phillip T; Stephens, Len R

    2017-11-02

    The PI3K signaling pathway regulates cell growth and movement and is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P 3 . PI(3,4,5)P 3 can be dephosphorylated by 3- or 5-phosphatases, the latter producing PI(3,4)P 2 . The PTEN tumor suppressor is thought to function primarily as a PI(3,4,5)P 3 3-phosphatase, limiting activation of this pathway. Here we show that PTEN also functions as a PI(3,4)P 2 3-phosphatase, both in vitro and in vivo. PTEN is a major PI(3,4)P 2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P 2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P 2 , which correlated with increased invadopodia in epidermal growth factor (EGF)-stimulated cells. PTEN deletion increased PI(3,4)P 2 levels in a mouse model of prostate cancer, and it inversely correlated with PI(3,4)P 2 levels across several EGF-stimulated prostate and breast cancer lines. These results point to a role for PI(3,4)P 2 in the phenotype caused by loss-of-function mutations or deletions in PTEN. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Personalised Peer-Supported Learning: The Peer-to-Peer Learning Environment (P2PLE)

    Science.gov (United States)

    Corneli, Joseph; Mikroyannidis, Alexander

    2011-01-01

    The Peer-to-Peer Learning Environment (P2PLE) is a proposed approach to helping learners co-construct their learning environment using recommendations about people, content, and tools. The work draws on current research on PLEs, and participant observation at the Peer-to-Peer University (P2PU). We are particularly interested in ways of eliciting…

  2. Roles for PI(3,5)P2 in nutrient sensing through TORC1

    Science.gov (United States)

    Jin, Natsuko; Mao, Kai; Jin, Yui; Tevzadze, Gela; Kauffman, Emily J.; Park, Sujin; Bridges, Dave; Loewith, Robbie; Saltiel, Alan R.; Klionsky, Daniel J.; Weisman, Lois S.

    2014-01-01

    TORC1, a conserved protein kinase, regulates cell growth in response to nutrients. Localization of mammalian TORC1 to lysosomes is essential for TORC1 activation. Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), an endosomal signaling lipid, is implicated in insulin-dependent stimulation of TORC1 activity in adipocytes. This raises the question of whether PI(3,5)P2 is an essential general regulator of TORC1. Moreover, the subcellular location where PI(3,5)P2 regulates TORC1 was not known. Here we report that PI(3,5)P2 is required for TORC1 activity in yeast and regulates TORC1 on the vacuole (lysosome). Furthermore, we show that the TORC1 substrate, Sch9 (a homologue of mammalian S6K), is recruited to the vacuole by direct interaction with PI(3,5)P2, where it is phosphorylated by TORC1. Of importance, we find that PI(3,5)P2 is required for multiple downstream pathways via TORC1-dependent phosphorylation of additional targets, including Atg13, the modification of which inhibits autophagy, and phosphorylation of Npr1, which releases its inhibitory function and allows nutrient-dependent endocytosis. These findings reveal PI(3,5)P2 as a general regulator of TORC1 and suggest that PI(3,5)P2 provides a platform for TORC1 signaling from lysosomes. PMID:24478451

  3. Modulation of P2X7 Receptor during Inflammation in Multiple Sclerosis

    NARCIS (Netherlands)

    Amadio, Susanna; Parisi, Chiara; Piras, Eleonora; Fabbrizio, Paola; Apolloni, Savina; Montilli, Cinzia; Luchetti, S.; Ruggieri, Serena; Gasperini, Claudio; Laghi-Pasini, Franco; Battistini, Luca; Volonté, Cinzia

    2017-01-01

    Multiple sclerosis (MS) is characterized by macrophage accumulation and inflammatory infiltrates into the CNS contributing to demyelination. Because purinergic P2X7 receptor (P2X7R) is known to be abundantly expressed on cells of the hematopoietic lineage and of the nervous system, we further

  4. Expression of the house dust mite allergen Der p 2 in the baker's yeast Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Hakkaart, G. A.; Harmsen, M. M.; Chua, K. Y.; Thomas, W. R.; Aalberse, R. C.; van Ree, R.

    1998-01-01

    BACKGROUND AND RESULTS: The major house dust mite allergen Der p 2 was expressed as a recombinant mature protein in the baker's yeast Saccharomyces cerevisiae. The yeast produces the protein fused to the invertase signal peptide, leading to the secretion of Der p 2 as a soluble protein into the

  5. P2X7 on mouse T cells: one channel, many functions

    Directory of Open Access Journals (Sweden)

    Björn eRissiek

    2015-05-01

    Full Text Available The P2X7 receptor is an adenosine triphosphate (ATP-gated cation channel that is expressed by several cells of the immune system. P2X7 is best known for its proinflammatory role in promoting inflammasome formation and release of mature IL-1β by innate immune cells. Mounting evidence indicates that P2X7 is also an important regulatory receptor of murine and human T cell functions. Murine T cells express a sensitive splice variant of P2X7 that can be activated either by non-covalent binding of ATP or, in the presence of nicotinamide adenine dinucleotide (NAD+, by its covalent ADP-ribosylation catalyzed by the ecto-ADP-ribosyltransferase ARTC2.2. Prolonged activation of P2X7 by either one of these pathways triggers the induction of T cell death. Conversely, lower concentrations of ATP can activate P2X7 to enhance T cell proliferation and production of IL-2. In this review we will highlight the molecular and cellular consequences of P2X7 activation on mouse T cells and its versatile role in T cell homeostasis and activation. Further, we will discuss important differences in the function of P2X7 on human and murine T cells.

  6. Residue level description of in vivo self-association of Plasmodium falciparum P2.

    Science.gov (United States)

    Mishra, Pushpa; Sharma, Shobhona; Hosur, Ramakrishna V

    2014-04-01

    Plasmodium falciparum P2 (PfP2) is a ribosomal stalk protein. It also performs extra ribosomal novel functions that seem to be associated with homo oligomerization . Previous in vitro studies have demonstrated that the protein has a high tendency to self-associate predominantly into an 8-mer. In vitro Heteronuclear Single Quantum Coherence (HSQC) of the pure recombinant protein (rPfP2) and its in-cell (Escherichia coli) HSQC spectrum has very similar features, indicating that the protein intrinsically, both inside the cell and under in vitro conditions, has similar aggregation tendencies. In view of this, we have characterized here the folding and concomitant self-association of rPfP2, using an in vitro dissociation-association strategy. We observed that the residue stretch, (Met31-Leu44) of the rPfP2, mapping to Met1-Leu14 of PfP2 protein acts as a nucleation site for helix formation and subsequent self-association. Further association appears to be driven by hydrophobic and complimentary electrostatic charge interactions on the surfaces formed. One stretch of rPfP2, (Ile97-Ala116), always remains floppy, and this may serve as "hinge" for protein segmental motions. Based on these, we have proposed a possible model for rPfP2 self-association into an 8-mer.

  7. Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media.

    Science.gov (United States)

    Rexhaj, Emrush; Pireva, Agim; Paoloni-Giacobino, Ariane; Allemann, Yves; Cerny, David; Dessen, Pierre; Sartori, Claudio; Scherrer, Urs; Rimoldi, Stefano F

    2015-10-01

    Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 μM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans. Copyright © 2015 the American Physiological Society.

  8. ATP analogues with modified phosphate chains and their selectivity for rat P2X(2) and P2X(2/3) receptors

    Czech Academy of Sciences Publication Activity Database

    Spelta, V.; Mekhalfia, A.; Rejman, Dominik; Thompson, M.; Blackburn, G. M.; North, R. A.

    2003-01-01

    Roč. 140, č. 6 (2003), s. 1027-1034 ISSN 0007-1188 Institutional research plan: CEZ:AV0Z4055905 Keywords : P2X receptors * electrophysiology * phosphate chain Subject RIV: CC - Organic Chemistry Impact factor: 3.611, year: 2003

  9. PRNGAWASAN TERHADAP P2KP-3 DI TATARAN MASYARAKAT KOTA BANDAR LAMPUNG

    Directory of Open Access Journals (Sweden)

    Upik Hamidah

    2014-04-01

    Full Text Available Dalam P2KP merupakan dana publik yang diwakafkan oleh pemerintah Indonesia kepada masyarakat di lokasi sasaaran P2KP. yang dalam pengaturan dan pengelolaannya melibatkan berbagai pihak. Dalam pengaturan dan pelaksanaannya diperlukan adanya pengawasan. Permasalahan dalam penelitian ini bagaimanakah pengaturan dan pelaksanaan pengawasan terhadap P2KP di tataran masyarakat. Hasil penelitian meneunjukan bahwa pengaturan pengawasan P2KP sangat ketat, berdasarkan kesepakatan bersama pemerintah Indonesia dan Bank Dunia, meliputi pengawasan intern dan pengaawasan extern. Tetapi tidak melibatkan pemerintah daerah. Pengawasan bersiafat educative atau pengawasan bertujuan untuk mendidik masyarakat pelaku P2KP di tataran masyarakat untuk bekerja dengan baik dan jujur. Dalam pengaturannya belum ada nampak adanya Standar Oprasional Prosedur pengawasan, sehingga dikhawatirkan dalam pelaksanaan pengawasan akan tumpang tindih.

  10. Common variants in P2RY11 are associated with narcolepsy

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Kawashima, Minae; Faraco, Juliette

    2011-01-01

    Americans). We identify a SNP in the 3' untranslated region of P2RY11, the purinergic receptor subtype P2Y11 gene, which is associated with narcolepsy (rs2305795, combined P = 6.1 × 10¿¹°, odds ratio = 1.28, 95% CI 1.19-1.39, n = 5689). The disease-associated allele is correlated with reduced expression...... of P2RY11 in CD8(+) T lymphocytes (339% reduced, P = 0.003) and natural killer (NK) cells (P = 0.031), but not in other peripheral blood mononuclear cell types. The low expression variant is also associated with reduced P2RY11-mediated resistance to ATP-induced cell death in T lymphocytes (P = 0.......0007) and natural killer cells (P = 0.001). These results identify P2RY11 as an important regulator of immune-cell survival, with possible implications in narcolepsy and other autoimmune diseases....

  11. Effective role of CaO/P2O5 ratio on SiO2-CaO-P2O5 glass system

    Directory of Open Access Journals (Sweden)

    P. Kiran

    2017-05-01

    Full Text Available In the present work, the effect of the CaO/P2O5 ratio on the composition of sol-gel synthesized 58SiO2-(19 − xP2O5–(23 + xCaO (x = 0, 5, 10 and 15 mol% glass samples was studied. Further, the effect of NBO/BO ratio on hydroxy carbonated apatite layer (HCA forming ability based on dissolution behavior in simulated body fluid (SBF solution was also investigated. CaO/P2O5 ratios of synthesized glass samples were 1.2, 2, 3.6, and 9.5, respectively. NBO/BO ratios were obtained using Raman spectroscopic analysis as 0.58, 1.20, 1.46, and 1.78, respectively. All samples were soaked in the SBF solution for 7 days. The calculated weight losses of these samples were 58%, 64%, 83%, and 89% for corresponding NBO/BO ratios. The increase in CaO/P2O5 ratio increases the NBO/BO ratios. However, the increase in NBO/BO ratio increases HCA forming ability of SBF treated samples. The HCA crystalline layer formation was confirmed through X-ray Diffraction (XRD, Transmission Electron Microscopy (TEM, Scanning Electron Microscopy (SEM, Raman and Infrared spectroscopic analysis. Higher CaO/P2O5 ratio favors the increase in HCA formation for SBF treated calcium phospho silicate glasses.

  12. Cloning and pharmacological characterization of the dog P2X7 receptor.

    Science.gov (United States)

    Roman, S; Cusdin, F S; Fonfria, E; Goodwin, J A; Reeves, J; Lappin, S C; Chambers, L; Walter, D S; Clay, W C; Michel, A D

    2009-11-01

    Human and rodent P2X7 receptors exhibit differences in their sensitivity to antagonists. In this study we have cloned and characterized the dog P2X7 receptor to determine if its antagonist sensitivity more closely resembles the human or rodent orthologues. A cDNA encoding the dog P2X7 receptor was isolated from a dog heart cDNA library, expressed in U-2 OS cells using the BacMam viral expression system and characterized in electrophysiological, ethidium accumulation and radioligand binding studies. Native P2X7 receptors were examined by measuring ATP-stimulated interleukin-1beta release in dog and human whole blood. The dog P2X7 receptor was 595 amino acids long and exhibited high homology (>70%) to the human and rodent orthologues although it contained an additional threonine at position 284 and an amino acid deletion at position 538. ATP possessed low millimolar potency at dog P2X7 receptors. 2'-&3'-O-(4benzoylbenzoyl) ATP had slightly higher potency but was a partial agonist. Dog P2X7 receptors possessed relatively high affinity for a number of selective antagonists of the human P2X7 receptor although there were some differences in potency between the species. Compound affinities in human and dog blood exhibited a similar rank order of potency as observed in studies on the recombinant receptor although absolute potency was considerably lower. Dog recombinant and native P2X7 receptors display a number of pharmacological similarities to the human P2X7 receptor. Thus, dog may be a suitable species for assessing target-related toxicity of antagonists intended for evaluation in the clinic.

  13. The role of P2X7R purinoreceptor in osteosarcoma

    Directory of Open Access Journals (Sweden)

    Manish Yadav

    2015-12-01

    Full Text Available Osteosarcoma is the most common type of bone cancer, which appears mainly in the metaphysis of long bones, especially in males between the age of 0–14 years. Malignancy usually emerges with the abnormal growth of tumor-forming bone cells. These tumor cells act like new bones that are responsible for the spread of sarcoma throughout the bone matrix. In this review, we focused on the expression and function of the P2X7 receptor (P2X7R as a therapeutic target in osteosarcoma malignancy. Two known human P2X7R functional splice variants in osteosarcoma cell growth are the full length P2X7RA and the truncated P2X7RB. The stimulation of growth is attributed to an increase (i in the mobilization of Ca2+ ions, and (ii in the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1 activity. Furthermore, Te85 P2X7RA+B cells caused membrane depolarization and spontaneous release of extracellular adenosine triphosphate (ATP. The P2X7R agonist, benzoyl adenosine triphosphate (BzATP, may increase the liberation of ATP and this may be regulated by P2X7R. As a result, cell proliferation occurs with the spread of osteosarcoma throughout the bone matrix. BzATP also increases cell growth and activates NFATc1 to make it cancerous. In this review, we have highlighted the crucial role of the P2X7R purinoreceptor in osteosarcoma pathogenesis. It is an upstream regulator of all paths that may inhibit the receptor activator of nuclear factor kappa-B ligand (RANKL and a mechanistic target of rapamycin (mTOR blockers. This review suggests that P2X7R is an attractive therapeutic target for osteosarcoma.

  14. P2X7 receptor-dependent tuning of gut epithelial responses to infection.

    Science.gov (United States)

    Huang, Szu-Wei; Walker, Catherine; Pennock, Joanne; Else, Kathryn; Muller, Werner; Daniels, Michael Jd; Pellegrini, Carolina; Brough, David; Lopez-Castejon, Gloria; Cruickshank, Sheena M

    2017-02-01

    Infection and injury of the gut are associated with cell damage and release of molecules such as extracellular adenosine 5'-triphosphate (ATP), which is recognised by the purinergic P2X7 receptor (P2X7R). P2X7R is widely expressed in the gut by antigen-presenting cells (APCs) and epithelial cells, but the role of the P2X7R on epithelial cells is poorly understood. We investigated P2X7R in intestinal epithelium in vitro and in vivo using two model infections, Toxoplasma gondii and Trichinella spiralis. Lipopolysaccharide and ATP treatment of intestinal epithelial cells and infection with T. gondii in vitro did not promote inflammasome-associated interleukin-1β (IL-1β) or IL-18 secretion, but promoted C-C motif chemokine ligand 5 (CCL5), tumour necrosis factor-α and IL-6 production that were significantly reduced when the P2X7R was blocked. Similarly, in vivo, infection with either T. spiralis or T. gondii induced rapid upregulation of epithelial CCL5 in wild-type (wild-type (WT)) mice that was significantly reduced in P2X7R -/- littermate controls. The effects of reduced epithelial CCL5 were assayed by investigating recruitment of dendritic cells (DCs) to the epithelium. Infection induced a rapid recruitment of CD11c + CD103 + DC subsets into the epithelial layer of WT mice but not P2X7R -/- mice. In vitro chemotaxis assays and bone marrow chimeras demonstrated the importance of epithelial P2X7R in DC recruitment. P2X7R signalling in epithelial cells mediates chemokine responses to promote initiation of host immunity to infection.

  15. P2X7 receptor cross-talk regulates ATP-induced pannexin 1 internalization.

    Science.gov (United States)

    Boyce, Andrew K J; Swayne, Leigh Anne

    2017-06-13

    In the nervous system, extracellular ATP levels transiently increase in physiological and pathophysiological circumstances, effecting key signalling pathways in plasticity and inflammation through purinergic receptors. Pannexin 1 (Panx1) forms ion- and metabolite-permeable channels that mediate ATP release and are particularly enriched in the nervous system. Our recent study demonstrated that elevation of extracellular ATP triggers Panx1 internalization in a concentration- and time-dependent manner. Notably, this effect was sensitive to inhibition of ionotropic P2X7 purinergic receptors (P2X7Rs). Here, we report our novel findings from the detailed investigation of the mechanism underlying P2X7R-Panx1 cross-talk in ATP-stimulated internalization. We demonstrate that extracellular ATP triggers and is required for the clustering of P2X7Rs and Panx1 on Neuro2a cells through an extracellular physical interaction with the Panx1 first extracellular loop (EL1). Importantly, disruption of P2X7R-Panx1 clustering by mutation of tryptophan 74 within the Panx1 EL1 inhibits Panx1 internalization. Notably, P2X7R-Panx1 clustering and internalization are independent of P2X7R-associated intracellular signalling pathways (Ca 2+ influx and Src activation). Further analysis revealed that cholesterol is required for ATP-stimulated P2X7R-Panx1 clustering at the cell periphery. Taken together, our data suggest that extracellular ATP induces and is required for Panx1 EL1-mediated, cholesterol-dependent P2X7R-Panx1 clustering and endocytosis. These findings have important implications for understanding the role of Panx1 in the nervous system and provide important new insights into Panx1-P2X7R cross-talk. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  16. Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage.

    Science.gov (United States)

    Cisneros-Mejorado, Abraham; Gottlieb, Miroslav; Cavaliere, Fabio; Magnus, Tim; Koch-Nolte, Friederich; Scemes, Eliana; Pérez-Samartín, Alberto; Matute, Carlos

    2015-05-01

    The role of P2X7 receptors and pannexin-1 channels in ischemic damage remains controversial. Here, we analyzed their contribution to postanoxic depolarization after ischemia in cultured neurons and in brain slices. We observed that pharmacological blockade of P2X7 receptors or pannexin-1 channels delayed the onset of postanoxic currents and reduced their slope, and that simultaneous inhibition did not further enhance the effects of blocking either one. These results were confirmed in acute cortical slices from P2X7 and pannexin-1 knockout mice. Oxygen-glucose deprivation in cortical organotypic cultures caused neuronal death that was reduced with P2X7 and pannexin-1 blockers as well as in organotypic cultures derived from mice lacking P2X7 and pannexin 1. Subsequently, we used transient middle cerebral artery occlusion to monitor the neuroprotective effect of those drugs in vivo. We found that P2X7 and pannexin-1 antagonists, and their ablation in knockout mice, substantially attenuated the motor symptoms and reduced the infarct volume to ~50% of that in vehicle-treated or wild-type animals. These results show that P2X7 receptors and pannexin-1 channels are major mediators of postanoxic depolarization in neurons and of brain damage after ischemia, and that they operate in the same deleterious signaling cascade leading to neuronal and tissue demise.

  17. Important roles of P2Y receptors in the inflammation and cancer of digestive system.

    Science.gov (United States)

    Wan, Han-Xing; Hu, Jian-Hong; Xie, Rei; Yang, Shi-Ming; Dong, Hui

    2016-05-10

    Purinergic signaling is important for many biological processes in humans. Purinoceptors P2Y are widely distributed in human digestive system and different subtypes of P2Y receptors mediate different physiological functions from metabolism, proliferation, differentiation to apoptosis etc. The P2Y receptors are essential in many gastrointestinal functions and also involve in the occurrence of some digestive diseases. Since different subtypes of P2Y receptors are present on the same cell of digestive organs, varying subtypes of P2Y receptors may have opposite or synergetic functions on the same cell. Recently, growing lines of evidence strongly suggest the involvement of P2Y receptors in the pathogenesis of several digestive diseases. In this review, we will focus on their important roles in the development of digestive inflammation and cancer. We anticipate that as the special subtypes of P2Y receptors are studied in depth, specific modulators for them will have good potentials to become promising new drugs to treat human digestive diseases in the near future.

  18. Orientation of Zn3P2 films via phosphidation of Zn precursors

    Science.gov (United States)

    Katsube, Ryoji; Nose, Yoshitaro

    2017-02-01

    Orientation of solar absorber is an important factor to achieve high efficiency of thin film solar cells. In the case of Zn3P2 which is a promising absorber of low-cost and high-efficiency solar cells, (110)/(001) orientation was only reported in previous studies. We have successfully prepared (101)-oriented Zn3P2 films by phosphidation of (0001)-oriented Zn films at 350 °C. The phosphidation mechanism of Zn is discussed through STEM observations on the partially-reacted sample and the consideration of the relationship between the crystal structures of Zn and Zn3P2 . We revealed that (0001)-oriented Zn led to nucleation of (101)-oriented Zn3P2 due to the similarity in atomic arrangement between Zn and Zn3P2 . The electrical resistivity of the (101)-oriented Zn3P2 film was lower than those of (110)/(001)-oriented films, which is an advantage of the phosphidation technique to the growth processes in previous works. The results in this study demonstrated that well-conductive Zn3P2 films could be obtained by controlling orientations of crystal grains, and provide a guiding principle for microstructure control in absorber materials.

  19. P2X7 receptor-mediated analgesia in cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; D. Schwab, Samantha; Frøsig-Jørgensen, Majbrit

    2015-01-01

    for cancer-induced bone pain. The P2X7 receptor (P2X7R) is involved in a variety of cellular functions and has been linked to both inflammatory and neuropathic pain. Here we study the analgesic potential of P2X7 receptor antagonism in a rat model of cancer-induced bone pain. In cancer-bearing animals, the P2....... The results suggest that the P2X7R is involved in the mechanisms of cancer-induced bone pain, and that P2X7R antagonism might be a useful analgesic target. No effect was observed in sham or naïve animals, indicating that the P2X7R-mediated effect is state-dependent, and might therefore be an advantageous......X7R antagonist A839977 attenuated dorsal horn neuronal responses in a modality and intensity specific way. Spinal application of 0.4mg/kg and 1.2mg/kg A839977 significantly reduced the evoked responses to high intensity mechanical and thermal stimulation, whereas no effect was seen in response...

  20. Rab5 regulates internalisation of P2X4 receptors and potentiation by ivermectin.

    Science.gov (United States)

    Stokes, Leanne

    2013-03-01

    The P2X4 receptor is an ATP-gated ion channel expressed in neurons, endothelia and immune cells. Plasma membrane expression of P2X4 is regulated by dynamin-dependent endocytosis, and this study identifies a Rab5-dependent pathway of receptor internalisation. Expression of Rab5 constructs altered the distribution of P2X4 in HEK-293 cells, and both constitutive internalisation and agonist-induced desensitisation of P2X4 were increased by co-expression of wild-type Rab5 or constitutively active Rab5 (Q79L). Expression of inactive dynamin K44A and Rab5 S34N constructs abolished agonist-induced desensitisation, suggesting internalisation as the underlying mechanism. Blocking P2X4 internalisation in this way also abolished potentiation of ATP-induced currents by the allosteric modulator ivermectin. This suggests that the dynamin-Rab5 internalisation pathway is essential for the ivermectin potentiation effect. In agreement with this hypothesis, the co-expression of wild-type dynamin, wild-type Rab5 or active Rab5 (Q79L) could increase the potentiation of the ATP-induced P2X4 response by ivermectin. These findings highlight Rab5 GTPase as a key regulator of P2X4 receptor cell surface expression and internalisation.

  1. Two disparate ligand binding sites in the human P2Y1 receptor

    Science.gov (United States)

    Zhang, Dandan; Gao, Zhan-Guo; Zhang, Kaihua; Kiselev, Evgeny; Crane, Steven; Wang, Jiang; Paoletta, Silvia; Yi, Cuiying; Ma, Limin; Zhang, Wenru; Han, Gye Won; Liu, Hong; Cherezov, Vadim; Katritch, Vsevolod; Jiang, Hualiang; Stevens, Raymond C.; Jacobson, Kenneth A.; Zhao, Qiang; Wu, Beili

    2015-01-01

    In response to adenosine 5′-diphosphate, the P2Y1 receptor (P2Y1R) facilitates platelet aggregation, and thus serves as an important antithrombotic drug target. Here we report the crystal structures of the human P2Y1R in complex with a nucleotide antagonist MRS2500 at 2.7Å resolution, and with a non-nucleotide antagonist BPTU at 2.2Å resolution. The structures reveal two distinct ligand binding sites, providing atomic details of P2Y1R’s unique ligand binding modes. MRS2500 recognizes a binding site within the seven transmembrane bundle of P2Y1R, which, however, is different in shape and location from the nucleotide binding site in previously determined P2Y12R structure. BPTU binds to an allosteric pocket on the external receptor interface with the lipid bilayer, making it the first structurally characterized selective G protein-coupled receptor (GPCR) ligand located entirely outside of the helical bundle. These high-resolution insights into P2Y1R should enable discovery of new orthosteric and allosteric antithrombotic drugs with reduced adverse effects. PMID:25822790

  2. Single-nucleotide polymorphisms in the P2X7 receptor gene are associated with post-menopausal bone loss and vertebral fractures

    DEFF Research Database (Denmark)

    Rye Jørgensen, Niklas; Husted, Lise Bjerre; Skarratt, Kristen K

    2012-01-01

    to bone mass and fracture incidence in post-menopausal women. A total of 1694 women (aged 45-58) participating in the Danish Osteoporosis Prevention Study were genotyped for 12 functional P2X7 receptor variants. Bone mineral density was determined at baseline and after 10 years. In addition, vertebral...... had increased bone loss. In contrast, the Gln460Arg polymorphism was associated with protection against bone loss. The Ala348Thr polymorphism was associated with a lower vertebral fracture incidence 10 years after menopause. Finally, we developed a risk model, which integrated P2RX7 genotypes. Using...

  3. Impaired P2X signalling pathways in renal microvascular myocytes in genetic hypertension

    KAUST Repository

    Gordienko, Dmitri V.

    2014-12-16

    Aims P2X receptors (P2XRs) mediate sympathetic control and autoregulation of renal circulation triggering preglomerular vasoconstriction, which protects glomeruli from elevated pressures. Although previous studies established a casual link between glomerular susceptibility to hypertensive injury and decreased preglomerular vascular reactivity to P2XR activation, the mechanisms of attenuation of the P2XR signalling in hypertension remained unknown. We aimed to analyse molecular mechanisms of the impairment of P2XR signalling in renal vascular smooth muscle cells (RVSMCs) in genetic hypertension. Methods and results We compared the expression of pertinent genes and P2XR-linked Ca2+ entry and Ca2+ release mechanisms in RVSMCs of spontaneously hypertensive rats (SHRs) and their normotensive controls, Wistar Kyoto (WKY) rats. We found that, in SHR RVSMCs, P2XR-linked Ca2+ entry and Ca2+ release from the sarcoplasmic reticulum (SR) are both significantly reduced. The former is due to down-regulation of the P2X1 subunit. The latter is caused by a decrease of the SR Ca2+ load. The SR Ca2+ load reduction is caused by attenuated Ca2+ uptake via down-regulated sarco-/endoplasmic reticulum Ca2+-ATPase 2b and elevated Ca2+ leak from the SR via ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors. Spontaneous activity of these Ca2+-release channels is augmented due to up-regulation of RyR type 2 and elevated IP3 production by up-regulated phospholipase C-β1. Conclusions Our study unravels the cellular and molecular mechanisms of attenuation of P2XR-mediated preglomerular vasoconstriction that elevates glomerular susceptibility to harmful hypertensive pressures. This provides an important impetus towards understanding of the pathology of hypertensive renal injury.

  4. Increased platelet activation and thrombosis in transgenic mice expressing constitutively active P2Y12 receptor

    Science.gov (United States)

    Zhang, Y.; Ye, J.; Hu, L.; Zhang, S.; Zhang, S.H.; Li, Y.; Kunapuli, S.P.; Ding, Z.

    2012-01-01

    Summary Background In our previous in vitro study we reported a constitutively active chimeric P2Y12 receptor (cP2Y12) and found AR-C78511 is a potent inverse agonist at this receptor. The role of this cP2Y12 receptor in platelet activation and thrombosis is not clear. Objectives To investigate the physiological implications of the constitutively active P2Y12 receptor in platelet activation, thrombus formulation and evaluate the antiplatelet activity of AR-C78511 as an inverse agonist. Methods and Results We generated transgenic mice conditionally and platelet-specifically expressing cP2Y12. High expression of cP2Y12 receptor in platelets increased platelet reactivity as evidenced by increased platelet aggregation in response to multiple platelet agonists. Moreover, transgenic mice displayed shortened bleeding time, more rapid and stable thrombus formation in mesenteric artery injured with FeCl3. The constitutive activity of cP2Y12 in platelets was confirmed by decreased platelet cAMP levels and constitutive Akt phosphorylation in the absence of agonists. AR-C78511 reversed the cAMP decrease in transgenic mouse platelets, and exhibited superior antiplatelet effect over AR-C69931MX in transgenic mice. Conclusions These findings further emphasize the importance of P2Y12 in platelet activation, hemostasis and thrombosis, as well as the prothrombotic role of constitutive activity of P2Y12. Our data also validates the in vivo inverse agonist activity of AR-C78511 and confirms its superior antiplatelet activity over neutral antagonist. PMID:22906019

  5. Increased P2X7R expression in atrial cardiomyocytes of caveolin-1 deficient mice.

    Science.gov (United States)

    Barth, K; Pfleger, C; Linge, A; Sim, J A; Surprenant, A; Steinbronn, N; Strasser, R H; Kasper, M

    2010-07-01

    It has recently been shown in epithelial cells that the ATP-gated ion channel P2X7R is in part, associated with caveolae and colocalized with caveolin-1. In the present study of the mouse heart, we show for the first time, using immunohistochemistry and cryoimmunoelectron microscopy, that P2X7R is expressed in atrial cardiomyocytes and in cardiac microvascular endothelial cells, but not in the ventricle cardiomyocytes. Furthermore, biochemical data indicate the presence of two forms of P2X7R, the classical glycosylated 80 kDa isoform and a protein with the molecular weight of 56 kDa, in both cardiomyocytes and endothelial cells of the mouse heart. The functionality of both proteins in heart cells is still unclear. In cardiac tissue homogenates derived from caveolin-1 deficient mice (cav-1(-/-)), an increase of the P2Xrx7 mRNA and P2X7R protein (80 kDa) was found, particularly in atrial samples. In addition, P2rx7(-/-) mice showed enhanced protein levels of caveolin-1 in their atrial tissues. Although the details of cellular mechanisms that underlie the relationship between caveolin-1 and P2X7R in atrial cardiomyocytes and the electrophysiological consequences of the increased P2X7R expression in atrial cells of cav-1(-/-) mice remain to be elucidated, the cardiomyopathy detectable in cav-1(-/-) mice is possibly related to a disturbed crosstalk between P2X7R and caveolin-1 in different heart cell populations.

  6. Environmental management maturity of local and multinational high-technology corporations located in Brazil: the role of business internationalization in pollution prevention

    Directory of Open Access Journals (Sweden)

    Giovanna Maialle

    2016-06-01

    Full Text Available Abstract This paper identifies and characterizes the environmental maturity level of local and multinational high-technology corporations located in Brazil. This characterization is achieved by discussing the adoption of environmental management practices and considering aspects of the productive process stage. An eight-case study was conducted through data triangulation using interviews with employees in diverse organizational areas, direct observations and secondary data. The results indicate the differences in environmental positioning among the studied corporations with a predominance of preventive practices, i.e., an emphasis on eco-efficiency and compliance with legislation. It was also noted that environmental concerns in the corporations are related to internationalization and, in some cases, to the pressure exerted by corporations that represent the brand of the products produced in Brazil. Moreover, the adoption of environmental practices based on the productive process stage supported the environmental maturity classifications of the studied companies.

  7. Ant Colony Algorithms for the Resolution of Semantic Searches in P2P Networks

    OpenAIRE

    Krynicki, Kamil Krzysztof

    2016-01-01

    [EN] The long-lasting trend in the field of computation of stress and resource distribution has found its way into computer networks via the concept of peer-to-peer (P2P) connectivity. P2P is a symmetrical model, where each network node is enabled a comparable range of capacities and resources. It stands in a stark contrast to the classical, strongly asymmetrical client-server approach. P2P, originally considered only a complimentary, server-side structure to the straightforward client-server...

  8. Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors

    Science.gov (United States)

    Pankratov, Yuriy

    2017-01-01

    Communication between neuronal and glial cells is important for neural plasticity. P2X receptors are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons and/or glia. Recent data show that postsynaptic P2X receptors underlie slow neuromodulatory actions rather than fast synaptic transmission at brain synapses. Here, we review these findings with a particular focus on the release of ATP by astrocytes and the diversity of postsynaptic P2X-mediated modulation of synaptic strength and plasticity in the CNS. PMID:28845311

  9. Targeting of the P2X7 receptor in pancreatic cancer and stellate cells

    DEFF Research Database (Denmark)

    Giannuzzo, Andrea; Saccomano, Mara; Napp, Joanna

    2016-01-01

    The ATP-gated receptor P2X7 (P2X7R) is involved in regulation of cell survival and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer and new markers and therapeutic targets are needed. PDAC is characterized by a complex tumour microenvironment, which...... into nude mice and tumour growth was followed noninvasively by bioluminescence imaging. AZ10606120-treated mice showed reduced bioluminescence compared to saline-treated mice. Immunohistochemical analysis confirmed P2X7R expression in cancer and PSC cells, and in metaplastic/neoplastic acinar and duct...

  10. PIP kinases define PI4,5P2 signaling specificity by association with effectors

    OpenAIRE

    Choi, Suyong; Thapa, Narendra; Tan, Xiaojun; Hedman, Andrew C.; Anderson, Richard A.

    2015-01-01

    Phosphatidylinositol 4,5-bisphosphate (PI4,5P2) is an essential lipid messenger with roles in all eukaryotes and most aspects of human physiology. By controlling the targeting and activity of its effectors, PI4,5P2 modulates processes, such as cell migration, vesicular trafficking, cellular morphogenesis, signaling and gene expression. In cells, PI4,5P2 has a much higher concentration than other phosphoinositide species and its total content is largely unchanged in response to extracellular s...

  11. P2X7R/cryopyrin inflammasome axis inhibition reduces neuroinflammation after SAH.

    Science.gov (United States)

    Chen, Sheng; Ma, Qingyi; Krafft, Paul R; Hu, Qin; Rolland, William; Sherchan, Prativa; Zhang, Jianmin; Tang, Jiping; Zhang, John H

    2013-10-01

    Neuroinflammation contributes to the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Cytotoxic events following SAH, such as extracellular accumulation of adenosine triphosphate (ATP), may activate the P2X purinoceptor 7 (P2X7R)/cryopyrin inflammasome axis, thus inducing the proinflammatory cytokine IL-1β/IL-18 secretion. We therefore hypothesized that inhibition of P2X7R/cryopyrin inflammasome axis would ameliorate neuroinflammation after SAH. In the present study, SAH was induced by the endovascular perforation in rats. Small interfering RNAs (siRNAs) of P2X7R or cryopyrin were administered intracerebroventricularly 24h before SAH. Brilliant blue G (BBG), a non-competitive antagonist of P2X7R, was administered intraperitoneally 30min following SAH. Post-assessments including SAH severity score, neurobehavioral test, brain water content, Western blot and immunofluorescence, were performed. Administration of P2X7R and cryopyrin siRNA as well as pharmacologic blockade of P2X7R by BBG ameliorated neurological deficits and brain edema at 24h following SAH. Inhibition of P2X7R/cryopyrin inflammasome axis suppressed caspase-1 activation, which subsequently decreased maturation of IL-1β/IL-18. To investigate the link between P2X7R and cryopyrin inflammasome in vivo, Benzoylbenzoyl-ATP (BzATP), a P2X7R agonist, was given to lipopolysaccharide (LPS) primed naive rats with scramble or cryopyrin siRNAs. In LPS-primed naive rats, BzATP induced caspase-1 activation and mature IL-1β release were neutralized by cryopyrin siRNA. Thus, the P2X7R/cryopyrin inflammasome axis may contribute to neuroinflammation via activation of caspase-1 and thereafter mature IL-1β/IL-18 production following SAH. Therapeutic interventions targeting P2X7R/cryopyrin pathway may be a novel approach to ameliorate EBI following SAH. © 2013.

  12. Activation of P2X7R and downstream effects in bleomycin treated lung epithelial cells.

    Science.gov (United States)

    Bläsche, Robert; Ebeling, Georg; Perike, Srikanth; Weinhold, Karina; Kasper, Michael; Barth, Kathrin

    2012-03-01

    Changes in intracellular calcium concentration [Ca(2+)](i) are believed to influence the proliferation and differentiation of airway epithelial cells both in vivo and in vitro. In the present study, using mouse alveolar epithelial E10 cells, we demonstrated that the treatment of lung epithelial cells with BLM resulted in elevated intracellular Ca(2+) levels. BLM further increased P2rx7 mRNA expression and P2X7R protein levels, paralleled by increased PKC-β1 levels. BLM treatment or stimulation of the P2X7R with the P2X7R agonist BzATP induced translocation of PKC-β1 from the cytoplasm to the membrane. The expression of PKC-β1 was repressed by the P2X7R inhibitor oxATP, suggesting that PKC-β1 is downstream of P2X7R activation. Furthermore, cells exposed to BLM contained increased amounts of P2X7R and PKC-β1 in Cav-1 containing lipid raft fractions. The comparison of lung tissues from wild-type and P2rx7(-/-) mice revealed decreased protein and mRNA levels of PKC-β1 and CaM as well as decreased immunoreactivity for PKC-β1. The knockdown of P2X7R in alveolar epithelial cells resulted also in a loss of PKC-β1. These data suggest that the effect of P2X7R on expression of PKC-β1 detected in alveolar epithelial cells is also functioning in the animal model. Immunohistochemical evaluation of fibrotic lungs derived from a BLM-induced mouse model revealed a strong increase in PKC-β1 immunoreactivity. The present experiments demonstrated that the increased expression of P2X7R influences PKC-β1. We predict that increased Ca(2+) concentration stimulates PKC-β1, whereas the prerequisite for activating PKC-β1 after P2X7R increase remained to be determined. Our findings suggest that PKC-β1 is important in the pathogenesis of pulmonary fibrosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Aneurysms of the P2P Segment of Posterior Cerebral Artery: Case Report and Surgical Steps

    Directory of Open Access Journals (Sweden)

    Paulo Aguiar

    2014-01-01

    Full Text Available The posterior cerebral artery (PCA is divided into 4 segments: precommunicating segment (P1, postcommunicating segment (P2, quadrigeminal segment (P3, and calcarine segment (P4. Small aneurysms are more prevalent than large aneurysms in patients with ruptured aneurysms. P2 and P3 aneurysms are usually managed by the subtemporal approach. This is a case report of rupture saccular aneurysm of posterior cerebral artery on P2P segment. The authors show the surgical steps of these rare aneurysms with an illustrative case.

  14. Mobility Impact in Initializing Ring-Based P2P Systems over MANETs

    Directory of Open Access Journals (Sweden)

    Wei Ding

    2008-10-01

    Full Text Available With the encouragement from success of P2P systems in real world application, recently we have seen active research on synergy of P2P systems and mobile ad hoc networks. The paper proposes a solution for mobility disturbance problem in initialization of ring-based P2P systems over ad hoc networks. It is a decentralized ring construction protocol in presence of mobility. A Mobile Ring Ad-hoc Networks (MRAN protocol is presented. MRAN is an extension of RAN [1] under the mobile condition. Simulation result shows MRAN works well with mobility. Upper bound of maximum speed of moving nodes is investigated in simulation.

  15. Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors

    Directory of Open Access Journals (Sweden)

    Eric Boué-Grabot

    2017-01-01

    Full Text Available Communication between neuronal and glial cells is important for neural plasticity. P2X receptors are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons and/or glia. Recent data show that postsynaptic P2X receptors underlie slow neuromodulatory actions rather than fast synaptic transmission at brain synapses. Here, we review these findings with a particular focus on the release of ATP by astrocytes and the diversity of postsynaptic P2X-mediated modulation of synaptic strength and plasticity in the CNS.

  16. Application of risk analysis and geographic information system technologies to the prevention of diarrheal diseases in Nigeria.

    Science.gov (United States)

    Njemanze, P C; Anozie, J; Ihenacho, J O; Russell, M J; Uwaeziozi, A B

    1999-09-01

    Among the poor in developing countries, up to 20% of an infant's life experience may include diarrhea. This problem is spatially related to the lack of potable water at different sites. This project used risk analysis (RA) methods and geographic information system (GIS) technologies to evaluate the health impact of water source. Maps of Imo State, Nigeria were converted into digital form using ARC/INFO GIS software, and the resulting coverages included geology, hydrology, towns, and villages. A total of 11,537 diarrheal cases were reported. Thirty-nine water sources were evaluated. A computer modeling approach called probabilistic layer analysis (PLA) spatially displayed the water source at layers of geology, hydrology, population, environmental pollution, and electricity according to a color-coded five-point ranking. The water sources were categorized into A, B, and C based on the cumulative scores 19 for C. T-test showed revealed significant differences in diarrheal disease incidence between categories A, B, and C with mean +/- SEM values of 1.612 +/- 0.325, 6.257 +/- 0.408, and 15.608 +/- 2.151, respectively. The differences were significant between categories A and B (P = 0.0000022), A and C (P = 0.0000188), and B and C (P = 0.0011348). The PLA enabled estimation of the probability of the risk of diarrheal diseases occurring at each layer and solutions to eliminate these risks.

  17. Presynaptic inhibition of spontaneous acetylcholine release mediated by P2Y receptors at the mouse neuromuscular junction.

    Science.gov (United States)

    De Lorenzo, S; Veggetti, M; Muchnik, S; Losavio, A

    2006-09-29

    At the neuromuscular junction, ATP is co-released with the neurotransmitter acetylcholine (ACh) and once in the synaptic space, it is degraded to the presynaptically active metabolite adenosine. Intracellular recordings were performed on diaphragm fibers of CF1 mice to determine the action of extracellular ATP (100 muM) and the slowly hydrolysable ATP analog 5'-adenylylimidodiphosphate lithium (betagamma-imido ATP) (30 muM) on miniature end-plate potential (MEPP) frequency. We found that application of ATP and betagamma-imido ATP decreased spontaneous secretion by 45.3% and 55.9% respectively. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A(1) adenosine receptor antagonist and alpha,beta-methylene ADP sodium salt (alphabeta-MeADP), which is an inhibitor of ecto-5'-nucleotidase, did not prevent the inhibitory effect of ATP, demonstrating that the nucleotide is able to modulate spontaneous ACh release through a mechanism independent of the action of adenosine. Blockade of Ca(2+) channels by both, Cd(2+) or the combined application of nitrendipine and omega-conotoxin GVIA (omega-CgTx) (L-type and N-type Ca(2+) channel antagonists, respectively) prevented the effect of betagamma-imido ATP, indicating that the nucleotide modulates Ca(2+) influx through the voltage-dependent Ca(2+) channels related to spontaneous secretion. betagamma-Imido ATP-induced modulation was antagonized by the non-specific P2 receptor antagonist suramin and the P2Y receptor antagonist 1-amino-4-[[4-[[4-chloro-6-[[3(or4)-sulfophenyl] amino]-1,3,5-triazin-2-yl]amino]-3-sulfophenyl] amino]-9,10-dihydro-9,10-dioxo-2-anthracenesulfonic acid (reactive blue-2), but not by pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt (PPADS), which has a preferential antagonist effect on P2X receptors. Pertussis toxin and N-ethylmaleimide (NEM), which are blockers of G(i/o) proteins, prevented the action of the nucleotide, suggesting that the effect is mediated by P2Y receptors

  18. Impact of ticagrelor on P2Y1 and P2Y12 localization and on cholesterol levels in platelet plasma membrane.

    Science.gov (United States)

    Rabani, Vahideh; Montange, Damien; Meneveau, Nicolas; Davani, Siamak

    2017-10-11

    Ticagrelor is an antiplatelet agent that inhibits platelet activation via P2Y12 antagonism. There are several studies showing that P2Y12 needs lipid rafts to be activated, but there are few data about how ticagrelor impacts lipid raft organization. Therefore, we aimed to investigate how ticagrelor could impact the distribution of cholesterol and consequently alter the organization of lipid rafts on platelet plasma membranes. We identified cholesterol-enriched raft fractions in platelet membranes by quantification of their cholesterol levels. Modifications in cholesterol and protein profiles (Flotillin 1, Flotillin 2, CD36, P2Y1, and P2Y12) were studied in platelets stimulated by ADP, treated by ticagrelor, or both. In ADP-stimulated and ticagrelor-treated groups, we found a decreased level of cholesterol in raft fractions of platelet plasma membrane compared to the control group. In addition, the peak of cholesterol in different experimental groups changed its localization on membrane fractions. In the control group, it was situated on fraction 2, while in ADP-stimulated platelets, it was located in fractions 3 to 5, and in fraction 4 in ticagrelor-treated group. The proteins studied also showed changes in their level of expression and localization in fractions of plasma membrane. Cholesterol levels of plasma membranes have a direct role in the organization of platelet membranes and could be modified by stimulation or drug treatment. Since ticagrelor and ADP both changed lipid composition and protein profile, investigating the lipid and protein composition of platelet membranes is of considerable importance as a focus for further research in anti-platelet management.

  19. Phosphoinositide 5-phosphatase activities control cell motility in glioblastoma: Two phosphoinositides PI(4,5)P2 and PI(3,4)P2 are involved.

    Science.gov (United States)

    Ramos, Ana Raquel; Elong Edimo, William's; Erneux, Christophe

    2018-01-01

    Inositol polyphosphate 5-phosphatases or phosphoinositide 5-phosphatases (PI 5-phosphatases) are enzymes that can act on soluble inositol phosphates and/or phosphoinositides (PIs). Several PI 5-phosphatases have been linked to human genetic diseases, in particular the Lowe protein or OCRL which is mutated in the Lowe syndrome. There are 10 different members of this family and 9 of them can use PIs as substrate. One of these substrates, PI(3,4,5)P3 binds to specific PH domains and recruits as effectors specific proteins to signaling complexes. Protein kinase B is one target protein and activation of the kinase will have a major impact on cell proliferation, survival and cell metabolism. Two other PIs, PI(4,5)P2 and PI(3,4)P2, are produced or used as substrates of PI 5-phosphatases (OCRL, INPP5B, SHIP1/2, SYNJ1/2, INPP5K, INPP5J, INPP5E). The inositol lipids may influence many aspects of cytoskeletal organization, lamellipodia formation and F-actin polymerization. PI 5-phosphatases have been reported to control cell migration, adhesion, polarity and cell invasion particularly in cancer cells. In glioblastoma, reducing SHIP2 expression can positively or negatively affect the speed of cell migration depending on the glioblastoma cell type. The two PI 5-phosphatases SHIP2 or SKIP could be localized at the plasma membrane and can reduce either PI(3,4,5)P3 or PI(4,5)P2 abundance. In the glioblastoma 1321 N1 cells, SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. End-Users' Product Preference Across Three Multipurpose Prevention Technology Delivery Forms: Baseline Results from Young Women in Kenya and South Africa.

    Science.gov (United States)

    Weinrib, Rachel; Minnis, Alexandra; Agot, Kawango; Ahmed, Khatija; Owino, Fred; Manenzhe, Kgahlisho; Cheng, Helen; van der Straten, Ariane

    2018-01-01

    A multipurpose prevention technology (MPT) that combines HIV and pregnancy prevention is a promising women's health intervention, particularly for young women. However, little is known about the drivers of acceptability and product choice for MPTs in this population. This paper explores approval ratings and stated choice across three different MPT delivery forms among potential end-users. The Trio Study was a mixed-methods study in women ages 18-30 that examined acceptability of three MPT delivery forms: oral tablets, injections, and vaginal ring. Approval ratings and stated choice among the products was collected at baseline. Factors influencing stated product choice were explored using multivariable multinomial logistic regression. The majority (62%) of women in Trio stated they would choose injections, 27% would choose tablets and 11% would choose the ring. Significant predictors of choice included past experience with similar contraceptive delivery forms, age, and citing frequency of use as important. Ring choice was higher for older (25-30) women than for younger (18-24) women (aRR = 3.1; p < 0.05). These results highlight the importance of familiarity in MPT product choice of potential for variations in MPT preference by age.

  1. Hazardous Materials Pharmacies - A Vital Component of a Robust P2 Program

    International Nuclear Information System (INIS)

    McCarter, S.

    2006-01-01

    Integrating pollution prevention (P2) into the Department of Energy Integrated Safety Management (ISM) - Environmental Management System (EMS) approach, required by DOE Order 450.1, leads to an enhanced ISM program at large and complex installations and facilities. One of the building blocks to integrating P2 into a comprehensive environmental and safety program is the control and tracking of the amounts, types, and flow of hazardous materials used on a facility. Hazardous materials pharmacies (typically called HazMarts) provide a solid approach to resolving this issue through business practice changes that reduce use, avoid excess, and redistribute surplus. If understood from concept to implementation, the HazMart is a powerful tool for reducing pollution at the source, tracking inventory storage, controlling usage and flow, and summarizing data for reporting requirements. Pharmacy options can range from a strict, single control point for all hazardous materials to a virtual system, where the inventory is user controlled and reported over a common system. Designing and implementing HazMarts on large, diverse installations or facilities present a unique set of issues. This is especially true of research and development (R and D) facilities where the chemical use requirements are extensive and often classified. There are often multiple sources of supply; a wide variety of chemical requirements; a mix of containers ranging from small ampoules to large bulk storage tanks; and a wide range of tools used to track hazardous materials, ranging from simple purchase inventories to sophisticated tracking software. Computer systems are often not uniform in capacity, capability, or operating systems, making it difficult to use a server-based unified tracking system software. Each of these issues has a solution or set of solutions tied to fundamental business practices. Each requires an understanding of the problem at hand, which, in turn, requires good communication among all

  2. Probenecid directly impairs activation of the canine P2X7 receptor.

    Science.gov (United States)

    Bartlett, Rachael; Stokes, Leanne; Curtis, Stephen J; Curtis, Belinda L; Sluyter, Ronald

    2017-12-02

    The current study aimed to determine if probenecid could directly impair the canine P2X7 receptor, a ligand-gated cation channel activated by extracellular adenosine 5'-triphosphate (ATP). Patch clamp measurements demonstrated that probenecid impairs ATP-induced inward currents in HEK-293 cells expressing canine P2X7. Flow cytometric measurements of ethidium + uptake into HEK-293 cells expressing canine P2X7 showed that probenecid impairs ATP-induced pore formation in a concentration-dependent manner, with a half maximal inhibitory concentration of 158 µM. Finally, ELISA measurements revealed that probenecid impairs ATP-induced interleukin-1β release in dog blood. In conclusion, this study reveals that probenecid can directly impair canine P2X7 activation.

  3. Expression, purification, crystallization and structure of human adipocyte lipid-binding protein (aP2)

    International Nuclear Information System (INIS)

    Marr, Eric; Tardie, Mark; Carty, Maynard; Brown Phillips, Tracy; Wang, Ing-Kae; Soeller, Walt; Qiu, Xiayang; Karam, George

    2006-01-01

    The crystal structure of human adipocyte lipid-binding protein (aP2) with a bound palmitate is reported at 1.5 Å resolution. Human adipocyte lipid-binding protein (aP2) belongs to a family of intracellular lipid-binding proteins involved in the transport and storage of lipids. Here, the crystal structure of human aP2 with a bound palmitate is described at 1.5 Å resolution. Unlike the known crystal structure of murine aP2 in complex with palmitate, this structure shows that the fatty acid is in a folded conformation and that the loop containing Phe57 acts as a lid to regulate ligand binding by excluding solvent exposure to the central binding cavity

  4. Porous Photocatalytic Membrane Microreactor (P2M2): A new reactor concept for photochemistry

    NARCIS (Netherlands)

    Aran, H.C.; Salamon, David; Rijnaarts, Timon; Rijnaarts, T.; Mul, Guido; Wessling, Matthias; Lammertink, Rob G.H.

    2011-01-01

    In this study, a new membrane microreactor concept for multiphase photocatalytic reactions is demonstrated. Microfabrication, photocatalyst immobilization and surface modification steps were performed to develop a Porous Photocatalytic Membrane Microreactor (P2M2). This concept benefits from a

  5. A Local Scalable Distributed EM Algorithm for Large P2P Networks

    Data.gov (United States)

    National Aeronautics and Space Administration — his paper describes a local and distributed expectation maximization algorithm for learning parameters of Gaussian mixture models (GMM) in large peer-to-peer (P2P)...

  6. Up-regulation of P2X7 receptor-mediated inhibition of GABA uptake by nerve terminals of the human epileptic neocortex.

    Science.gov (United States)

    Barros-Barbosa, Aurora R; Fonseca, Ana L; Guerra-Gomes, Sónia; Ferreirinha, Fátima; Santos, Agostinho; Rangel, Rui; Lobo, M Graça; Correia-de-Sá, Paulo; Cordeiro, J Miguel

    2016-01-01

    Thirty percent of patients with epilepsy are refractory to medication. The majority of these patients have mesial temporal lobe epilepsy (MTLE). This prompts for new pharmacologic targets, like ATP-mediated signaling pathways, since the extracellular levels of the nucleotide dramatically increase during in vitro epileptic seizures. In this study, we investigated whether sodium-dependent high-affinity γ-aminobutyric acid (GABA) and glutamate uptake by isolated nerve terminals of the human neocortex could be modulated by ATP acting via slow-desensitizing P2X7 receptor (P2X7R). Modulation of [(3) H]GABA and [(14) C]glutamate uptake by ATP, through activation of P2X7R, was investigated in isolated nerve terminals of the neocortex of cadaveric controls and patients with drug-resistant epilepsy (non-MTLE or MTLE) submitted to surgery. Tissue density and distribution of P2X7R in the human neocortex was assessed by Western blot analysis and immunofluorescence confocal microscopy. The P2X7R agonist, 2'(3')-O-(4-benzoylbenzoyl)ATP (BzATP, 3-100 μm) decreased [(3) H]GABA and [(14) C]glutamate uptake by nerve terminals of the neocortex of controls and patients with epilepsy. The inhibitory effect of BzATP (100 μm) was prevented by the selective P2X7R antagonist, A-438079 (3 μm). Down-modulation of [(14) C]glutamate uptake by BzATP (100 μm) was roughly similar in controls and patients with epilepsy, but the P2X7R agonist inhibited more effectively [(3) H]GABA uptake in the epileptic tissue. Neocortical nerve terminals of patients with epilepsy express higher amounts of the P2X7R protein than control samples. High-frequency cortical activity during epileptic seizures releases huge amounts of ATP, which by acting on low-affinity slowly desensitizing ionotropic P2X7R, leads to down-modulation of neuronal GABA and glutamate uptake. Increased P2X7R expression in neocortical nerve terminals of patients with epilepsy may, under high-frequency firing, endure GABA signaling and

  7. Exploring user experience and technology acceptance for a fall prevention system: results from a randomized clinical trial and a living lab.

    Science.gov (United States)

    Vaziri, Daryoush D; Aal, Konstantin; Ogonowski, Corinna; Von Rekowski, Thomas; Kroll, Michael; Marston, Hannah R; Poveda, Rakel; Gschwind, Yves J; Delbaere, Kim; Wieching, Rainer; Wulf, Volker

    2016-01-01

    Falls are common in older adults and can result in serious injuries. Due to demographic changes, falls and related healthcare costs are likely to increase over the next years. Participation and motivation of older adults in fall prevention measures remain a challenge. The iStoppFalls project developed an information and communication technology (ICT)-based system for older adults to use at home in order to reduce common fall risk factors such as impaired balance and muscle weakness. The system aims at increasing older adults' motivation to participate in ICT-based fall prevention measures. This article reports on usability, user-experience and user-acceptance aspects affecting the use of the iStoppFalls system by older adults. In the course of a 16-week international multicenter study, 153 community-dwelling older adults aged 65+ participated in the iStoppFalls randomized controlled trial, of which half used the system in their home to exercise and assess their risk of falling. During the study, 60 participants completed questionnaires regarding the usability, user experience and user acceptance of the iStoppFalls system. Usability was measured with the System Usability Scale (SUS). For user experience the Physical Activity Enjoyment Scale (PACES) was applied. User acceptance was assessed with the Dynamic Acceptance Model for the Re-evaluation of Technologies (DART). To collect more detailed data on usability, user experience and user acceptance, additional qualitative interviews and observations were conducted with participants. Participants evaluated the usability of the system with an overall score of 62 (Standard Deviation, SD 15.58) out of 100, which suggests good usability. Most users enjoyed the iStoppFalls games and assessments, as shown by the overall PACES score of 31 (SD 8.03). With a score of 0.87 (SD 0.26), user acceptance results showed that participants accepted the iStoppFalls system for use in their own home. Interview data suggested that certain

  8. DESENSITIZATION PROPERTIES OF P2X3 RECEPTORS SHAPING PAIN SIGNALLING

    Directory of Open Access Journals (Sweden)

    Rashid eGiniatullin

    2013-12-01

    Full Text Available ATP-gated P2X3 receptors are mostly expressed by nociceptive sensory neurons and participate in transduction of pain signals. P2X3 receptors show a combination of fast desensitization onset and slow recovery. Moreover, even low nanomolar agonist concentrations unable to evoke a response, can induce desensitization via a phenomenon called ‘high affinity desensitization’. We have also observed that recovery from desensitization is agonist-specific and can range from seconds to minutes. The recovery process displays unusually high temperature dependence. Likewise, recycling of P2X3 receptors in peri-membrane regions shows unexpectedly large temperature sensitivity. By applying kinetic modeling, we have previously shown that desensitization characteristics of P2X3 receptor are best explained with a cyclic model of receptor operation involving three agonist molecules binding a single receptor and that desensitization is primarily developing from the open receptor state. Mutagenesis experiments suggested that desensitization depends on a certain conformation of the ATP binding pocket and on the structure of the transmembrane domains forming the ion pore. Further molecular determinants of desensitization have been identified by mutating the intracellular N- and C-termini of P2X3 receptor. Unlike other P2X receptors, the P2X3 subtype is facilitated by extracellular calcium that acts via specific sites in the ectodomain neighboring the ATP binding pocket. Thus, substitution of serine275 in this region (called ‘left flipper’ converts the natural facilitation induced by extracellular calcium to receptor inhibition. Given such their strategic location in nociceptive neurons and unique desensitization properties, P2X3 receptors represent an attractive target for development of new analgesic drugs via promotion of desensitization aimed at suppressing chronic pain.

  9. Drug-like antagonists of P2Y receptors — from lead identification to drug development

    OpenAIRE

    Conroy, Sean; Kindon, Nicholas; Kellam, Barrie; Stocks, Michael

    2016-01-01

    P2Y receptors are expressed in virtually all cells and tissue types and mediate an astonishing array of biological functions, including platelet aggregation, smooth muscle cell proliferation, and immune regulation. The P2Y receptors belong to the G protein-coupled receptor superfamily and are composed of eight members encoded by distinct genes that can be subdivided into two groups on the basis of their coupling to specific G-proteins. Extensive research has been undertaken to find modulators...

  10. HFsub(1-x)2Rsub(x) 3P2O11 luminescent material

    International Nuclear Information System (INIS)

    Chenot, C.F.; Mathers, J.E.; Shaffer, F.N.

    1980-01-01

    A new compound corresponding to an oxide composition of 3:1 (HFsub(1-x)Zrsub(x))O 2 :P 2 O 5 . and having the empircal formula (HFsub(1-x)Zrsub(x)) 3 P 2 O 11 . where x is in the range of about 0 to 0.5. is an effective luminescent material for use in x-ray intensifying screens, and also an effective luminescent material host for Eusup(+2) blue emissions. (auth)

  11. Synthesis and structural characterization of Na2MnP2O7 crystal

    Indian Academy of Sciences (India)

    Unknown

    The starting mixture consists of manganese oxide, 85% orthophos- phoric acid and 2⋅5–5 M NaOH solution which acts as a mineralizer. Na2MnP2O7 crystals could be synthesized under the following molar ratio. Na2O : MnO : P2O5 = 3–5 : 0⋅5–0⋅75 : 12–16. The following reaction explains the synthesis of the compound.

  12. Critical Evaluation of P2X7 Receptor Antagonists in Selected Seizure Models

    Science.gov (United States)

    Fischer, Wolfgang; Franke, Heike; Krügel, Ute; Müller, Heiko; Dinkel, Klaus; Lord, Brian; Letavic, Michael A.; Henshall, David C.; Engel, Tobias

    2016-01-01

    The ATP-gated P2X7 receptor (P2X7R) is a non-selective cation channel which senses high extracellular ATP concentrations and has been suggested as a target for the treatment of neuroinflammation and neurodegenerative diseases. The use of P2X7R antagonists may therefore be a viable approach for treating CNS pathologies, including epileptic disorders. Recent studies showed anticonvulsant potential of P2X7R antagonists in certain animal models. To extend this work, we tested three CNS-permeable P2X7R blocker (Brilliant Blue G, AFC-5128, JNJ-47965567) and a natural compound derivative (tanshinone IIA sulfonate) in four well-characterized animal seizure models. In the maximal electroshock seizure threshold test and the pentylenetetrazol (PTZ) seizure threshold test in mice, none of the four compounds demonstrated anticonvulsant effects when given alone. Notably, in combination with carbamazepine, both AFC-5128 and JNJ-47965567 increased the threshold in the maximal electroshock seizure test. In the PTZ-kindling model in rats, useful for testing antiepileptogenic activities, Brilliant Blue G and tanshinone exhibited a moderate retarding effect, whereas the potent P2X7R blocker AFC-5128 and JNJ-47965567 showed a significant and long-lasting delay in kindling development. In fully kindled rats, the investigated compounds revealed modest effects to reduce the mean seizure stage. Furthermore, AFC-5128- and JNJ-47965567-treated animals displayed strongly reduced Iba 1 and GFAP immunoreactivity in the hippocampal CA3 region. In summary, our results show that P2X7R antagonists possess no remarkable anticonvulsant effects in the used acute screening tests, but can attenuate chemically-induced kindling. Further studies would be of interest to support the concept that P2X7R signalling plays a crucial role in the pathogenesis of epileptic disorders. PMID:27281030

  13. Point Mutation in the Mouse P2X7 Receptor Affects Intercellular Calcium Waves in Astrocytes

    Directory of Open Access Journals (Sweden)

    Sylvia O Suadicani

    2009-03-01

    Full Text Available Purinergic P2 receptors and gap junctions are two groups of proteins involved in the transmission of ICWs (intercellular calcium waves between astrocytes. The extent to which ICWs spread among these glial cells depends on the amount of ATP released, which can occur through membrane channels, as well as other pathways. Our previous studies have shown that the pore-forming P2X7R (P2X7 receptor contributes to the amplification of ICW spread by providing sites of ATP release through Panx1 (Pannexin1 channels. To gain insight into the signal transduction events mediating this response we compared the properties of the P2X7R–Panx1 complex in astrocytes from a mouse strain (C57Bl/6 containing a naturally occurring point mutation (P451L in the C-terminus of the P2X7R to that of non-mutated receptors (Balb/C mice. Electrophysiological, biochemical, pharmacological and fluorescence imaging techniques revealed that the P451L mutation located in the SH3 domain (a Src tyrosine kinase-binding site of the C-terminus of the P2X7R attenuates Panx1 currents, ATP release and the distance of ICW spread between astrocytes. Similar results were obtained when using the Src tyrosine inhibitor (PP2 and a membrane-permeant peptide spanning the P451L mutation of the P2X7R of the C57Bl6 astrocytes. These results support the participation of a tyrosine kinase of the Src family in the initial steps mediating the opening of Panx1 channels following P2X7R stimulation and in the transmission of calcium signals among astrocytes.

  14. Role of P2X7R in the development and progression of pulmonary hypertension.

    Science.gov (United States)

    Yin, Jie; You, Shuling; Liu, Haopeng; Chen, Li; Zhang, Chengdong; Hu, Hesheng; Xue, Mei; Cheng, Wenjuan; Wang, Ye; Li, Xinran; Shi, Yugen; Li, Nannan; Yan, Suhua; Li, Xiaolu

    2017-06-24

    Pulmonary arterial hypertension (PAH) is a devastating disease that lacks sufficient treatment. Studies have shown that the Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome contributes to PAH pathogenesis, but the role of the upstream molecular P2X 7 receptor (P2X 7 R) has remained unexplored. We investigated the role of P2X7R in the pathogenesis of PAH. PH was induced by a single subcutaneous injection of monocrotaline (MCT) (60 mg/kg) on left pneumonectomised Sprague-Dawley rats, as validated by significant increases in pulmonary artery pressure and vessel wall thickness. Marked P2X 7 R was detected by predominant PA immunostaining in lungs from PH rats. Western blot revealed a significant increase in the protein levels of P2X 7 R as well as NLRP3 and caspase-1 in the diseased lung tissue compared with normal tissue. The rats received A-740003 (a selective P2X 7 receptor antagonist, 30 mg/kg) daily starting from 1 week before or 2 weeks after MCT injection. Consequently, A-740003 reversed the NLRP3 inflammasome upregulation, significantly decreased the mean right ventricular (RV) pressure and RV hypertrophy, and reversed pulmonary arterial remodelling 4 weeks after MCT injection, as both a pretreatment and rescue intervention. Notably, A-740003 significantly reduced macrophage and pro-inflammatory cytokine levels, as measured via bronchoalveolar lavage. The recruitment of macrophages as well as collagen fibre deposition in the perivascular areas were also reduced, as confirmed by histological staining. P2X 7 R contributes to the pathogenesis of PH, probably in association with activation of the NLRP3 inflammasome. Blockade of P2X7R might be applied as a novel therapeutic approach for the treatment of PAH.

  15. Critical Evaluation of P2X7 Receptor Antagonists in Selected Seizure Models.

    Directory of Open Access Journals (Sweden)

    Wolfgang Fischer

    Full Text Available The ATP-gated P2X7 receptor (P2X7R is a non-selective cation channel which senses high extracellular ATP concentrations and has been suggested as a target for the treatment of neuroinflammation and neurodegenerative diseases. The use of P2X7R antagonists may therefore be a viable approach for treating CNS pathologies, including epileptic disorders. Recent studies showed anticonvulsant potential of P2X7R antagonists in certain animal models. To extend this work, we tested three CNS-permeable P2X7R blocker (Brilliant Blue G, AFC-5128, JNJ-47965567 and a natural compound derivative (tanshinone IIA sulfonate in four well-characterized animal seizure models. In the maximal electroshock seizure threshold test and the pentylenetetrazol (PTZ seizure threshold test in mice, none of the four compounds demonstrated anticonvulsant effects when given alone. Notably, in combination with carbamazepine, both AFC-5128 and JNJ-47965567 increased the threshold in the maximal electroshock seizure test. In the PTZ-kindling model in rats, useful for testing antiepileptogenic activities, Brilliant Blue G and tanshinone exhibited a moderate retarding effect, whereas the potent P2X7R blocker AFC-5128 and JNJ-47965567 showed a significant and long-lasting delay in kindling development. In fully kindled rats, the investigated compounds revealed modest effects to reduce the mean seizure stage. Furthermore, AFC-5128- and JNJ-47965567-treated animals displayed strongly reduced Iba 1 and GFAP immunoreactivity in the hippocampal CA3 region. In summary, our results show that P2X7R antagonists possess no remarkable anticonvulsant effects in the used acute screening tests, but can attenuate chemically-induced kindling. Further studies would be of interest to support the concept that P2X7R signalling plays a crucial role in the pathogenesis of epileptic disorders.

  16. FoxP2 expression in avian vocal learners and non-learners.

    Science.gov (United States)

    Haesler, Sebastian; Wada, Kazuhiro; Nshdejan, A; Morrisey, Edward E; Lints, Thierry; Jarvis, Eric D; Scharff, Constance

    2004-03-31

    Most vertebrates communicate acoustically, but few, among them humans, dolphins and whales, bats, and three orders of birds, learn this trait. FOXP2 is the first gene linked to human speech and has been the target of positive selection during recent primate evolution. To test whether the expression pattern of FOXP2 is consistent with a role in learned vocal communication, we cloned zebra finch FoxP2 and its close relative FoxP1 and compared mRNA and protein distribution in developing and adult brains of a variety of avian vocal learners and non-learners, and a crocodile. We found that the protein sequence of zebra finch FoxP2 is 98% identical with mouse and human FOXP2. In the avian and crocodilian forebrain, FoxP2 was expressed predominantly in the striatum, a basal ganglia brain region affected in patients with FOXP2 mutations. Strikingly, in zebra finches, the striatal nucleus Area X, necessary for vocal learning, expressed more FoxP2 than the surrounding tissue at post-hatch days 35 and 50, when vocal learning occurs. In adult canaries, FoxP2 expression in Area X differed seasonally; more FoxP2 expression was associated with times when song becomes unstable. In adult chickadees, strawberry finches, song sparrows, and Bengalese finches, Area X expressed FoxP2 to different degrees. Non-telencephalic regions in both vocal learning and non-learning birds, and in crocodiles, were less variable in expression and comparable with regions that express FOXP2 in human and rodent brains. We conclude that differential expression of FoxP2 in avian vocal learners might be associated with vocal plasticity.

  17. PON-P2: prediction method for fast and reliable identification of harmful variants.

    Directory of Open Access Journals (Sweden)

    Abhishek Niroula

    Full Text Available More reliable and faster prediction methods are needed to interpret enormous amounts of data generated by sequencing and genome projects. We have developed a new computational tool, PON-P2, for classification of amino acid substitutions in human proteins. The method is a machine learning-based classifier and groups the variants into pathogenic, neutral and unknown classes, on the basis of random forest probability score. PON-P2 is trained using pathogenic and neutral variants obtained from VariBench, a database for benchmark variation datasets. PON-P2 utilizes information about evolutionary conservation of sequences, physical and biochemical properties of amino acids, GO annotations and if available, functional annotations of variation sites. Extensive feature selection was performed to identify 8 informative features among altogether 622 features. PON-P2 consistently showed superior performance in comparison to existing state-of-the-art tools. In 10-fold cross-validation test, its accuracy and MCC are 0.90 and 0.80, respectively, and in the independent test, they are 0.86 and 0.71, respectively. The coverage of PON-P2 is 61.7% in the 10-fold cross-validation and 62.1% in the test dataset. PON-P2 is a powerful tool for screening harmful variants and for ranking and prioritizing experimental characterization. It is very fast making it capable of analyzing large variant datasets. PON-P2 is freely available at http://structure.bmc.lu.se/PON-P2/.

  18. High-pressure and high-temperature powder diffraction on molybdenum diphosphide, MoP2

    International Nuclear Information System (INIS)

    Soto, V.; Knorr, K.; Ehm, L.; Baehtz, C.; Winkler, B.; Avalos-Borja, M.

    2004-01-01

    The isothermal compressibility and bulk thermal expansion of molybdenum diphosphide, MoP 2 , were measured by in-situ X-ray powder diffraction from ambient conditions to 6.8 GPa and 839 K, respectively. A small anisotropy of the compressibilities in MoP 2 appears to be governed by non-bonding interactions in this layer-like material. The thermal expansion data are compared to molybdenum phosphide, MoP, which was measured to 1262 K. (orig.)

  19. Expression and characterization of natural-like recombinant Der p 2 for sublingual immunotherapy.

    Science.gov (United States)

    Bordas-Le Floch, Véronique; Bussières, Laetitia; Airouche, Sabi; Lautrette, Aurélie; Bouley, Julien; Berjont, Nathalie; Horiot, Stéphane; Huet, Axelle; Jain, Karine; Lemoine, Pierrick; Chabre, Henri; Batard, Thierry; Mascarell, Laurent; Baron-Bodo, Véronique; Tourdot, Sophie; Nony, Emmanuel; Moingeon, Philippe

    2012-01-01

    Recombinant allergens with a native conformation represent an alternative to natural extracts for immunotherapy and diagnostic purposes. We produced the Der p 2 mite allergen in Pichia pastoris and Escherichia coli. After purification by cation exchange chromatography, recombinant molecules were compared to their natural counterpart based upon structural (disulfide bonds, secondary structure, thermal stability) and immunological properties (antibody reactivity, basophil and T cell activation, tolerance induction in a murine sublingual immunotherapy model). The Der p 2.0101 isoform was confirmed to be prevalent in Dermatophagoides pteronyssinus extracts. It was then produced as a secreted molecule in P. pastoris or refolded from E. coli inclusion bodies. The yeast-expressed rDer p 2 molecule exhibits a natural-like disulfide bridge distribution and secondary structure, whereas the E. coli-derived rDer p 2 presents some heterogeneity in cysteine bonds and a lower stability following thermal stress. The two recombinant as well as natural Der p 2 molecules exhibit comparable IgE recognition and activate basophil and CD4+ T cells. Sublingual immunotherapy of nDer p 2- sensitized mice using either one of the rDer p 2 molecules efficiently decreases airway hyperresponsiveness as well as Th2 responses. Natural and recombinant Der p 2 molecules produced in P. pastoris and E. coli exhibit comparable immunological properties despite distinct structural features. Natural-like cysteine pairing is a critical parameter to identify stable, well-folded and homogenous proteins appropriate for immunotherapy and diagnostic purposes. Copyright © 2012 S. Karger AG, Basel.

  20. P2X7 receptor-deficient mice are susceptible to bone cancer pain

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Nielsen, Christian K.; Nasser, Arafat

    2011-01-01

    The purinergic P2X7 receptor is implicated in both neuropathic and inflammatory pain, and has been suggested as a possible target in pain treatment. However, the specific role of the P2X7 receptor in bone cancer pain is unknown. We demonstrated that BALB/cJ P2X7 receptor knockout (P2X7R KO) mice...... were susceptible to bone cancer pain and moreover had an earlier onset of pain-related behaviours compared with cancer-bearing, wild-type mice. Furthermore, acute treatment with the selective P2X7 receptor antagonist, A-438079, failed to alleviate pain-related behaviours in models of bone cancer pain...... with and without astrocyte activation (BALB/cJ or C3H mice inoculated with 4T1 mammary cancer cells or NCTC 2472 osteosarcoma cells, respectively), suggesting that astrocytic P2X7 receptors play a negligible role in bone cancer pain. The results support the hypothesis that bone cancer pain is a separate pain state...

  1. Extracellular ATP in the lymphohematopoietic system: P2Z purinoceptors and membrane permeabilization

    Directory of Open Access Journals (Sweden)

    Persechini P.M.

    1998-01-01

    Full Text Available The effects of extracellular nucleosides and nucleotides on many organs and systems have been recognized for almost 50 years. The effects of extracellular ATP (ATPo, UTPo, ADPo, and other agonists are mediated by P2 purinoceptors. One of the most dramatic effects of ATPo is the permeabilization of plasma membranes to low molecular mass solutes of up to 900 Da. This effect is evident in several cells of the lymphohematopoietic system and is supposed to be mediated by P2Z, an ATP4--activated purinoceptor. Here, we review some basic information concerning P2 purinoceptors and focus our attention on P2Z-associated phenomena displayed by macrophages. Using fluorescent dye uptake, measurement of free intracellular Ca2+ concentration and electrophysiological recordings, we elucidate some of the events that follow the application of ATP to the extracellular surface of macrophages. We propose a regulatory mechanism for the P2Z-associated permeabilization pore. The presence of P2 purinoceptors in cells of the lymphohematopoietic system makes them potential candidates to mediate immunoregulatory events

  2. Decentralized Scheduling Algorithm for DAG Based Tasks on P2P Grid

    Directory of Open Access Journals (Sweden)

    Piyush Chauhan

    2014-01-01

    Full Text Available Complex problems consisting of interdependent subtasks are represented by a direct acyclic graph (DAG. Subtasks of this DAG are scheduled by the scheduler on various grid resources. Scheduling algorithms for grid strive to optimize the schedule. Nowadays a lot of grid resources are attached by P2P approach. Grid systems and P2P model both are newfangled distributed computing approaches. Combining P2P model and grid systems we get P2P grid systems. P2P grid systems require fully decentralized scheduling algorithm, which can schedule interreliant subtasks among nonuniform computational resources. Absence of central scheduler caused the need for decentralized scheduling algorithm. In this paper we have proposed scheduling algorithm which not only is fruitful in optimizing schedule but also does so in fully decentralized fashion. Hence, this unconventional approach suits well for P2P grid systems. Moreover, this algorithm takes accurate scheduling decisions depending on both computation cost and communication cost associated with DAG’s subtasks.

  3. Music training enhances rapid plasticity of N1 and P2 source activation for unattended sounds

    Directory of Open Access Journals (Sweden)

    Miia eSeppänen

    2012-03-01

    Full Text Available Neurocognitive studies demonstrate that long-term musical training enhances the processing of unattended sounds. It is not clear, however, whether musical training modulates also rapid (within tens of minutes neural plasticity for sound encoding. To study this, we examined whether adult musicians display enhanced rapid neural plasticity when compared to nonmusicians. More specifically, we examined the modulation of P1, N1, and P2 responses to regular standard sounds in an oddball paradigm between unattended passive blocks which were separated by an active task. Source analysis for event-related potentials showed that N1 and P2 source activation decreased selectively in musicians already after fifteen minutes of passive exposure to sounds and that P2 source activation re-enhanced after the active task in musicians. Additionally, event-related potential (ERP analysis revealed that in both musicians and nonmusicians, P2 ERP amplitude enhanced after fifteen minutes of passive exposure but only at frontal electrodes. Furthermore, in musicians, N1 ERP enhanced after the active discrimination task but only at parietal electrodes. Musical training modulates the rapid plasticity reflected in N1 and P2 source activation for unattended regular standard sounds. Enhanced rapid plasticity of N1 and P2 might reflect the faster auditory perceptual learning in musicians when compared to nonmusicians.

  4. P2X7 receptor activation regulates rapid unconventional export of transglutaminase-2

    Science.gov (United States)

    Adamczyk, Magdalena; Griffiths, Rhiannon; Dewitt, Sharon; Knäuper, Vera; Aeschlimann, Daniel

    2015-01-01

    ABSTRACT Transglutaminases (denoted TG or TGM) are externalized from cells via an unknown unconventional secretory pathway. Here, we show for the first time that purinergic signaling regulates active secretion of TG2 (also known as TGM2), an enzyme with a pivotal role in stabilizing extracellular matrices and modulating cell–matrix interactions in tissue repair. Extracellular ATP promotes TG2 secretion by macrophages, and this can be blocked by a selective antagonist against the purinergic receptor P2X7 (P2X7R, also known as P2RX7). Introduction of functional P2X7R into HEK293 cells is sufficient to confer rapid, regulated TG2 export. By employing pharmacological agents, TG2 release could be separated from P2X7R-mediated microvesicle shedding. Neither Ca2+ signaling alone nor membrane depolarization triggered TG2 secretion, which occurred only upon receptor membrane pore formation and without pannexin channel involvement. A gain-of-function mutation in P2X7R associated with autoimmune disease caused enhanced TG2 externalization from cells, and this correlated with increased pore activity. These results provide a mechanistic explanation for a link between active TG2 secretion and inflammatory responses, and aberrant enhanced TG2 activity in certain autoimmune conditions. PMID:26542019

  5. Role of P2X7 Receptor in Pancreatic Cancer Progression

    DEFF Research Database (Denmark)

    Giannuzzo, Andrea

    in the extracellular compartment. Among all the purinergic receptors, P2X7 receptor (P2X7R), with its peculiar double-faced role in both cell death and cell proliferation, has been shown to be involved in the progression of some types of cancer. Thus, the aim of our study was to investigate the possible role of P2X7R...... in PDAC behaviour in vitro and in vivo. We detected a higher P2X7R protein level in several human PDAC cells compared to a “normal” human pancreatic duct epithelial cell line, which localized mostly on the plasma membrane. From the functional point of view, we observed that a sustained activation of the P......2X7 receptor using ATP and BzATP (a more potent agonist) resulted in a cytotoxic effect, mainly ascribed to necrosis. The allosteric inhibition of the receptor led to a drastic reduction in cell proliferation in all PDAC cell lines. Moreover, P2X7R showed a crucial role in PDAC cell migration...

  6. Monitoring and Resource Management in P2P Grid-Based Web Services

    Directory of Open Access Journals (Sweden)

    Djafri Laouni

    2012-12-01

    Full Text Available Gri