WorldWideScience

Sample records for reinvestment project trp

  1. TA 55 Reinvestment Project II Phase C Update Project Status May 23, 2017

    Energy Technology Data Exchange (ETDEWEB)

    Giordano, Anthony P. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-05-25

    The TA-55 Reinvestment Project (TRP) II Phase C is a critical infrastructure project focused on improving safety and reliability of the Los Alamos National Laboratory (LANL) TA-55 Complex. The Project recapitalizes and revitalizes aging and obsolete facility and safety systems providing a sustainable nuclear facility for National Security Missions.

  2. Project Reinvest: Invest in America's Future by Reinvesting in America's Community Colleges.

    Science.gov (United States)

    McCabe, Robert H.

    To help raise the level of funding for the nation's community colleges, Project Reinvest was created to help colleges communicate their role in solving the nation's problems and the importance of adequate funding. Specifically, the project seeks to encourage colleges' participation in efforts to develop a genuine understanding of their…

  3. American Recovery and Reinvestment Act: Clean Cities Project Awards

    Energy Technology Data Exchange (ETDEWEB)

    2016-08-01

    Each Clean Cities project award under the American Recovery and Reinvestment Act included a diverse group of stakeholders who worked together to lay the foundation for their communities to adopt alternative fuels and petroleum reduction strategies. This document provides a snapshot of the impact of each project and highlights the partners and Clean Cities coalitions who helped transform local and regional transportation markets through 25 projects impacting 45 states.

  4. NPD project portfolio selection using reinvestment strategy in competitive environment

    Directory of Open Access Journals (Sweden)

    Alireza Ghassemi

    2018-01-01

    Full Text Available This study aims to design a new model for selecting most fitting new product development projects in a pool of projects. To catch the best model, we assume new products will be introduced to the competitive markets. Also, we suppose the revenue yielded by completed projects can be reinvested on implementation of other projects. Other sources of financing are borrowing loans from banks and initial capital of the firm. These limited resources determine most evaluated projects to be performed. Several types of interactions among different projects are considered to make the chosen projects more like a portfolio. In addition, some numerical examples from the real world are provided to demonstrate the applicability of the proposed model. These examples show how the particular considerations in the suggested model affect the results.

  5. A socioeconomic assessment of Forest Service American Recovery and Reinvestment Act projects: eight case studies

    Science.gov (United States)

    Susan Charnley; Pamela J. Jakes; John Schelhas

    2011-01-01

    The American Recovery and Reinvestment Act of 2009 aimed to create jobs and jumpstart the economy while addressing the Nation’s social and environmental needs. The U.S. Department of Agriculture, Forest Service, received $1.15 billion in recovery funding to support projects in wildland fire management, capital improvement and maintenance, and biomass utilization. This...

  6. The New Mexico Technology Deployment Pilot Project: A technology reinvestment project. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-11-01

    The New Mexico Technology Deployment Project (NMTDP) has been in operation for slightly more than two years. As one of the original TRP projects, NMTDP had the charter to develop and validate a new model for technology extraction which emphasized focused technology collaboration, early industry involvement, and a strong dual use commercialization and productization emphasis. Taken in total, the first two years of the NMTDP have been exceptionally successful, surpassing the goals of the project. This report describes the accomplishments and evolution of the NMTDP to date and discusses the future potential of the project. Despite the end of federal funding, and a subsequent reduction in level of effort, the project partners are committed to continuation of the project.

  7. Designing a Successful Transportation Project: Lessons Learned from the Clean Cities American Recovery and Reinvestment Act Projects

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, K.; Singer, M.

    2017-09-01

    The largest source of funding for alternative fuel vehicle and infrastructure projects in the U.S. Department of Energy's Clean Cities program's history came from the American Recovery and Reinvestment Act (Recovery Act). In 2009, the 25 cost-share projects totaled nearly $300 million in federal government investment. This effort included the involvement of 50 Clean Cities coalitions and their nearly 700 stakeholder partners who provided an additional $500 million in matching funds to support projects in their local communities. In total, those 25 projects established 1,380 alternative fueling stations and put more than 9,000 alternative fuel and advanced technology vehicles on the road. Together, these projects displaced 154 million gasoline gallon equivalents (GGE) of petroleum and averted 254,000 tons of greenhouse gas (GHG) emissions, while supporting U.S. energy independence and contributing to regional economic development. During post-project interviews, project leaders consistently cited a number of key components - ranging from technical and logistical factors, to administrative capabilities - for accomplishing an effective and impactful project. This report summarizes the high-level project design and administrative considerations for conducting a successful transportation project.

  8. Designing a Successful Transportation Project: Lessons Learned from the Clean Cities American Recovery and Reinvestment Act Projects

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Kay L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Singer, Mark R. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2017-09-28

    The largest source of funding for alternative fuel vehicle and infrastructure projects in the U.S. Department of Energy's Clean Cities program's history came from the American Recovery and Reinvestment Act (Recovery Act). In 2009, the 25 cost-share projects totaled nearly $300 million in federal government investment. This effort included the involvement of 50 Clean Cities coalitions and their nearly 700 stakeholder partners who provided an additional $500 million in matching funds to support projects in their local communities. In total, those 25 projects established 1,380 alternative fueling stations and put more than 9,000 alternative fuel and advanced technology vehicles on the road. Together, these projects displaced 154 million gasoline gallon equivalents (GGE) of petroleum and averted 254,000 tons of greenhouse gas (GHG) emissions, while supporting U.S. energy independence and contributing to regional economic development. During post-project interviews, project leaders consistently cited a number of key components - ranging from technical and logistical factors, to administrative capabilities - for accomplishing an effective and impactful project. This report summarizes the high-level project design and administrative considerations for conducting a successful transportation project.

  9. A Review of the American Recovery and Reinvestment Act Smart Grid Projects and Their Implications for China

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xu [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Marnay, Chris [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Feng, Wei [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Zhou, Nan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Karali, Nihan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2017-06-21

    The Chinese government has paid growing attention to renewable energy development and has set ambitious goals for carbon dioxide (CO2) emissions reduction and energy savings. Smart grid (SG) technologies have been regarded as emerging ways to integrate renewable energy and to help achieve these climate and energy goals. This report first reviews completed SG demonstrations under the U.S. American Recovery and Reinvestment Act (ARRA); especially two key programs: the SG Investment Grant (SGIG) and the SG Demonstration Project (SGDP). Under the SGIG, the larger of the two programs, over $3.4 billion was used to help industry deploy existing advanced SG technologies and tools to improve grid performance and reduce costs. Including industry investment, a total of $8 billion was spent on 99 cost-shared projects, which involved more than 200 participating electric utilities and other organizations. These projects aimed to modernize the electric grid, strengthen cyber security, improve interoperability, and collect comprehensive data on SG operations and benefits.

  10. New Mexico Forest Inventory and Analysis: American Recovery and Reinvestment Act Project, Field Report: 2010-2012

    Science.gov (United States)

    Mary Stuever; John Capuano

    2014-01-01

    For a 3-year period, from 2010-2012, the New Mexico Forestry Division utilized contractors to collect Forest Inventory and Analysis (FIA) data in New Mexico. Funded through the American Recovery and Reinvestment Act, the State partnered with the Interior West FIA Program. Together, both agencies collected data on approximately 6,450 plots. This effort represents the...

  11. American Recovery and Reinvestment Act (ARRA) FEMP Technical Assistance for Geothermal Resource Evaluation Projects

    Energy Technology Data Exchange (ETDEWEB)

    Robert P. Breckenridge; Thomas R. Wood; Joel Renner

    2010-09-01

    The purpose of this document is to report on the evaluation of geothermal resource potential on and around three different United States (U. S.) Air Force Bases (AFBs): Nellis AFB and Air Force Range (AFR) in the State of Nevada (see maps 1 and 5), Holloman AFB in the State of New Mexico (see map 2), and Mountain Home AFB in the State of Idaho (see map 3). All three sites are located in semi-arid parts of the western U. S. The U. S. Air Force, through its Air Combat Command (ACC) located at Langley AFB in the State of Virginia, asked the Federal Energy Management Program (FEMP) for technical assistance to conduct technical and feasibility evaluations for the potential to identify viable geothermal resources on or around three different AFBs. Idaho National Laboratory (INL) is supporting FEMP in providing technical assistance to a number of different Federal Agencies. For this report, the three different AFBs are considered one project because they all deal with potential geothermal resource evaluations. The three AFBs will be evaluated primarily for their opportunity to develop a geothermal resource of high enough quality grade (i.e., temperature, productivity, depth, etc.) to consider the possibility for generation of electricity through a power plant. Secondarily, if the resource for the three AFBs is found to be not sufficient enough for electricity generation, then they will be described in enough detail to allow the base energy managers to evaluate if the resource is suitable for direct heating or cooling. Site visits and meetings by INL personnel with the staff at each AFB were held in late FY-2009 and FY-2010. This report provides a technical evaluation of the opportunities and challenges for developing geothermal resources on and around the AFBs. An extensive amount of literature and geographic information was evaluated as a part of this assessment. Resource potential maps were developed for each of the AFBs.

  12. 77 FR 5516 - Notice of a Project Waiver of the American Recovery and Reinvestment Act of 2009 (ARRA) to the...

    Science.gov (United States)

    2012-02-03

    ... funding current infrastructure construction, not to delay projects that are ``shovel ready'' by requiring... result in unreasonable delay and thus displace the ``shovel ready'' status for this project. To further...

  13. Entrepreneurial Saving Practices and Reinvestment

    NARCIS (Netherlands)

    Beck, Thorsten; Pamuk, Haki; Uras, Burak R.

    2017-01-01

    We use a novel enterprise survey to gauge the relationship between saving instruments and entrepreneurial reinvestment. We show that while most informal saving practices are not associated with a lower likelihood of reinvestment when compared with formal saving practices, there is a significantly

  14. TRP channels: an overview

    DEFF Research Database (Denmark)

    Pedersen, Stine Falsig; Owsianik, Grzegorz; Nilius, Bernd

    2005-01-01

    The TRP ("transient receptor potential") family of ion channels now comprises more than 30 cation channels, most of which are permeable for Ca2+, and some also for Mg2+. On the basis of sequence homology, the TRP family can be divided in seven main subfamilies: the TRPC ('Canonical') family......, the TRPV ('Vanilloid') family, the TRPM ('Melastatin') family, the TRPP ('Polycystin') family, the TRPML ('Mucolipin') family, the TRPA ('Ankyrin') family, and the TRPN ('NOMPC') family. The cloning and characterization of members of this cation channel family has exploded during recent years, leading...... to a plethora of data on the roles of TRPs in a variety of tissues and species, including mammals, insects, and yeast. The present review summarizes the most pertinent recent evidence regarding the structural and functional properties of TRP channels, focusing on the regulation and physiology of mammalian TRPs....

  15. American Recovery and Reinvestment Act (ARRA) Federal Energy Management Program Technical Assistance Project 282 Renewable Energy Opportunities at Fort Gordon, Georgia

    Energy Technology Data Exchange (ETDEWEB)

    Boyd, Brian K.; Gorrissen, Willy J.; Hand, James R.; Horner, Jacob A.; Orrell, Alice C.; Russo, Bryan J.; Weimar, Mark R.; Williamson, Jennifer L.; Nesse, Ronald J.

    2010-09-30

    This document provides an overview of renewable resource potential at Fort Gordon, based primarily upon analysis of secondary data sources supplemented with limited on-site evaluations. This effort focuses on grid-connected generation of electricity from renewable energy sources and also on ground source heat pumps for heating and cooling buildings. The effort was funded by the American Recovery and Reinvestment Act (ARRA) as follow-on to the 2005 Department of Defense (DoD) Renewables Assessment. The site visit to Fort Gordon took place on March 9, 2010.

  16. Comprehensive Energy Assessment: EE and RE Project Optimization Modeling for United States Pacific Command (USPACOM) American Recovery and Reinvestment Act (ARRA) FEMP Technical Assistance

    Energy Technology Data Exchange (ETDEWEB)

    Brigantic, Robert T.; Papatyi, Anthony F.; Perkins, Casey J.

    2010-09-30

    This report summarizes a study and corresponding model development conducted in support of the United States Pacific Command (USPACOM) as part of the Federal Energy Management Program (FEMP) American Reinvestment and Recovery Act (ARRA). This research was aimed at developing a mathematical programming framework and accompanying optimization methodology in order to simultaneously evaluate energy efficiency (EE) and renewable energy (RE) opportunities. Once developed, this research then demonstrated this methodology at a USPACOM installation - Camp H.M. Smith, Hawaii. We believe this is the first time such an integrated, joint EE and RE optimization methodology has been constructed and demonstrated.

  17. Nurse Reinvestment Act. Public Law.

    Science.gov (United States)

    Congress of the U.S., Washington, DC.

    This document contains the text of the Nurse Reinvestment Act, which amends the Public Health Service Act to address the increasing shortage of registered nurses by instituting a series of policies to improve nurse recruitment and nurse retention. Title I details two initiatives to boost recruitment of nurses. The first initiative includes the…

  18. TRP channels in kidney disease.

    NARCIS (Netherlands)

    Hsu, Y.J.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2007-01-01

    Mammalian TRP channel proteins form six-transmembrane cation-permeable channels that may be grouped into six subfamilies on the basis of amino acid sequence homology (TRPC, TRPV, TRPM, TRPA, TRPP, and TRPML). Recent studies of TRP channels indicate that they are involved in numerous fundamental cell

  19. TRP Channels in Human Prostate

    Directory of Open Access Journals (Sweden)

    Carl Van Haute

    2010-01-01

    Full Text Available This review gives an overview of morphological and functional characteristics in the human prostate. It will focus on the current knowledge about transient receptor potential (TRP channels expressed in the human prostate, and their putative role in normal physiology and prostate carcinogenesis. Controversial data regarding the expression pattern and the potential impact of TRP channels in prostate function, and their involvement in prostate cancer and other prostate diseases, will be discussed.

  20. Next generation sub-millimeter wave focal plane array coupling concepts: an ESA TRP project to develop multichroic focal plane pixels for future CMB polarization experiments

    Science.gov (United States)

    Trappe, N.; Bucher, M.; De Bernardis, P.; Delabrouille, J.; Deo, P.; DePetris, M.; Doherty, S.; Ghribi, A.; Gradziel, M.; Kuzmin, L.; Maffei, B.; Mahashabde, S.; Masi, S.; Murphy, J. A.; Noviello, F.; O'Sullivan, C.; Pagano, L.; Piacentini, F.; Piat, M.; Pisano, G.; Robinson, M.; Stompor, R.; Tartari, A.; van der Vorst, M.; Verhoeve, P.

    2016-07-01

    The main objective of this activity is to develop new focal plane coupling array concepts and technologies that optimise the coupling from reflector optics to the large number of detectors for next generation sub millimetre wave telescopes particularly targeting measurement of the polarization of the cosmic microwave background (CMB). In this 18 month TRP programme the consortium are tasked with developing, manufacturing and experimentally verifying a prototype multichroic pixel which would be suitable for the large focal plane arrays which will be demanded to reach the required sensitivity of future CMB polarization missions. One major development was to have multichroic operation to potentially reduce the required focal plane size of a CMB mission. After research in the optimum telescope design and definition of requirements based on a stringent science case review, a number of compact focal plane architecture concepts were investigated before a pixel demonstrator consisting of a planar mesh lens feeding a backend Resonant Cold Electron Bolometer RCEB for filtering and detection of the dual frequency signal was planned for manufacture and test. In this demonstrator the frequencies of the channels was chosen to be 75 and 105 GHz in the w band close to the peak CMB signal. In the next year the prototype breadboards will be developed to test the beams produced by the manufactured flat lenses fed by a variety of antenna configurations and the spectral response of the RCEBs will also be verified.

  1. American Recovery and Reinvestment Act (ARRA) Federal Energy Management Program Technical Assistance Project 281 Solar Hot Water Application Assessment for U.S. Army IMCOM-Southeast Region

    Energy Technology Data Exchange (ETDEWEB)

    Russo, Bryan J.; Chvala, William D.

    2010-09-30

    The Energy Independence and Security Act of 2007 requires installations (EISA) to install solar systems of sufficient capacity to provide 30% of service hot water in new construction and renovations where cost-effective. However, installations are struggling with how to implement solar hot water, and while several installations are installing solar hot water on a limited basis, paybacks remain long. Pacific Northwest National Laboratory (PNNL) was tasked to address this issue to help determine how best to implement solar hot water projects. This documents discusses the results of that project.

  2. The Positive Impacts Of American Reinvestment And Recovery Act (ARRA) Funding To The Waste Management Program On Hanford's Plateau Remediation Project

    International Nuclear Information System (INIS)

    Blackford, L.T.

    2010-01-01

    In April 2009, the Department of Energy (DOE) Richland Operations Office (RL) was allocated $1.6 billion (B) in ARRA funding to be applied to cleanup projects at the Hanford Site. DOE-RL selected projects to receive ARRA funding based on 3-criteria: creating/saving jobs, reducing the footprint of the Hanford Site, and reducing life-cycle costs for cleanup. They further selected projects that were currently covered under regulatory documents and existing prime contracts, which allowed work to proceed quickly. CH2M HILL Plateau Remediation Company (CHPRC) is a prime contractor to the DOE focused on the environmental cleanup of the DOE Hanford Site Central Plateau. CHPRC was slated to receive $1.36B in ARRA funding. As of January, 2010, CHPRC has awarded over $200 million (M) in subcontracts (64% to small businesses), created more that 1,100 jobs, and touched more than 2,300 lives - all in support of long-term objectives for remediation of the Central Plateau, on or ahead of schedule. ARRA funding is being used to accelerate and augment cleanup activities already underway under the baseline Plateau Remediation Contract (PRC). This paper details challenges and accomplishments using ARRA funding to meet DOE-RL objectives of creating/saving jobs, expediting cleanup, and reducing lifecycle costs for cleanup during the first months of implementation.

  3. Louisiana Speaks Regional Plan Vision Reinvestment Centers, UTM Zone 15N NAD83, Louisiana Recovery Authority (2007), [louisiana_speaks_vision_reinvestment_centers

    Data.gov (United States)

    Louisiana Geographic Information Center — This GIS shapefile data illustrates reinvestment centers included in the Louisiana Speaks Regional Plan Vision. Reinvestment centers highlight communities that...

  4. 76 FR 72449 - Notice of Buy American Waiver Under the American Recovery and Reinvestment Act of 2009

    Science.gov (United States)

    2011-11-23

    ... manufactured goods used in and incorporated into a project funded through the Academic Research Infrastructure... iron, steel, and manufactured goods used in and incorporated into a project funded through the Academic... Recovery Act projects funded by the Academic Research Infrastructure--Recovery and Reinvestment Program...

  5. 31 CFR 357.27 - Reinvestment.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Reinvestment. 357.27 Section 357.27 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE... AND BILLS HELD IN LEGACY TREASURY DIRECT Legacy Treasury Direct Book-Entry Securities System (Legacy...

  6. 75 FR 82217 - Community Reinvestment Act Regulations

    Science.gov (United States)

    2010-12-30

    ... Thrift Supervision 12 CFR Part 563e [Docket ID OTS-2010-0032] RIN 1550-AC45 Community Reinvestment Act... Federal Reserve System (Board); Federal Deposit Insurance Corporation (FDIC); Office of Thrift Supervision...) regulations to adjust the asset-size thresholds used to define ``small bank'' or ``small savings association...

  7. 75 FR 79278 - Community Reinvestment Act Regulations

    Science.gov (United States)

    2010-12-20

    ... Congressional intent that the funds have maximum impact and be targeted to States and local communities with the... communities affected by high levels of foreclosures and delinquencies. \\12\\ The Board also received over 650... Thrift Supervision 12 CFR Part 563e [Docket ID OTS-2010-0031] RIN 1550-AC42 Community Reinvestment Act...

  8. 76 FR 79529 - Community Reinvestment Act Regulations

    Science.gov (United States)

    2011-12-22

    ... ``agencies'') are amending their Community Reinvestment Act (CRA) regulations to adjust the asset-size... ``intermediate small savings association.'' As required by the CRA regulations, the adjustment to the threshold... Description of the Joint Final Rule The agencies' CRA regulations establish CRA performance standards for...

  9. 125I-[Tyr0,D-Trp8]somatostatin-14 binding sites in the locus coeruleus of the rat are located on both ascending and descending projecting noradrenergic cells

    International Nuclear Information System (INIS)

    Epelbaum, J.; Bluet-Pajot, M.T.; Llorens-Cortes, C.; Kordon, C.; Mounier, F.; Senut, M.C.; Videau, C.

    1990-01-01

    Radioautographic determinations of 125I-[Tyr0,D-Trp8]somatostatin-14 (125I-SRIF) binding sites were performed on frozen serial sections of the locus coeruleus (LC) of control rats and of rats subjected to either bilateral microinjections of 6 hydroxydopamine (6-OHDA) into the LC or unilateral microinjection into the ascending noradrenergic bundles. These experiments were performed in order to determine whether 125I-SRIF binding was localized to noradrenergic-containing cells and in which regions the cells which contain the binding sites are projecting. The extent of the lesions was assessed by measuring norepinephrine (NE) levels in the hippocampus (88% decrease as compared to sham-operated animals) for bilateral LC lesions and in the frontal cortex (87% reduction vs. contralateral side) for unilateral bundle lesions. In control rats, 125I-SRIF binding sites were restricted to the boundaries of the LC and followed closely the distribution of tyrosine hydroxylase-labeled cells. Three weeks after bilateral injections of 6-OHDA, 125I-SRIF binding decreased by 79% in all regions of the LC. In contrast, unilateral destruction of the ascending noradrenergic bundles resulted in a moderate decrease only in the middle part of the LC with a more important effect in the dorsal (55%) than in the ventral (24%) portion of the nucleus. These data demonstrate that: (1) most SRIF receptors in the LC are located in the vicinity of NE-containing cell bodies and (2) NE-containing cells bearing SRIF receptors project to the forebrain as well as to other terminal areas located more caudally in the brain. These data suggest a general role for SRIF in the control of the multiple functions of the LC

  10. TRP channel proteins and signal transduction.

    Science.gov (United States)

    Minke, Baruch; Cook, Boaz

    2002-04-01

    TRP channel proteins constitute a large and diverse family of proteins that are expressed in many tissues and cell types. This family was designated TRP because of a spontaneously occurring Drosophila mutant lacking TRP that responded to a continuous light with a transient receptor potential (hence TRP). In addition to responses to light, TRPs mediate responses to nerve growth factor, pheromones, olfaction, mechanical, chemical, temperature, pH, osmolarity, vasorelaxation of blood vessels, and metabolic stress. Furthermore, mutations in several members of TRP-related channel proteins are responsible for several diseases, such as several tumors and neurodegenerative disorders. TRP-related channel proteins are found in a variety of organisms, tissues, and cell types, including nonexcitable, smooth muscle, and neuronal cells. The large functional diversity of TRPs is also reflected in their diverse permeability to ions, although, in general, they are classified as nonselective cationic channels. The molecular domains that are conserved in all members of the TRP family constitute parts of the transmembrane domains and in most members also the ankyrin-like repeats at the NH2 terminal of the protein and a "TRP domain" at the COOH terminal, which is a highly conserved 25-amino acid stretch with still unknown function. All of the above features suggest that members of the TRP family are "special assignment" channels, which are recruited to diverse signaling pathways. The channels' roles and characteristics such as gating mechanism, regulation, and permeability are determined by evolution according to the specific functional requirements.

  11. Role of TRP Channels in Dinoflagellate Mechanotransduction.

    Science.gov (United States)

    Lindström, J B; Pierce, N T; Latz, M I

    2017-10-01

    Transient receptor potential (TRP) ion channels are common components of mechanosensing pathways, mainly described in mammals and other multicellular organisms. To gain insight into the evolutionary origins of eukaryotic mechanosensory proteins, we investigated the involvement of TRP channels in mechanosensing in a unicellular eukaryotic protist, the dinoflagellate Lingulodinium polyedra. BLASTP analysis of the protein sequences predicted from the L. polyedra transcriptome revealed six sequences with high similarity to human TRPM2, TRPM8, TRPML2, TRPP1, and TRPP2; and characteristic TRP domains were identified in all sequences. In a phylogenetic tree including all mammalian TRP subfamilies and TRP channel sequences from unicellular and multicellular organisms, the L. polyedra sequences grouped with the TRPM, TPPML, and TRPP clades. In pharmacological experiments, we used the intrinsic bioluminescence of L. polyedra as a reporter of mechanoresponsivity. Capsaicin and RN1734, agonists of mammalian TRPV, and arachidonic acid, an agonist of mammalian TRPV, TRPA, TRPM, and Drosophila TRP, all stimulated bioluminescence in L. polyedra. Mechanical stimulation of bioluminescence, but not capsaicin-stimulated bioluminescence, was inhibited by gadolinium (Gd 3+ ), a general inhibitor of mechanosensitive ion channels, and the phospholipase C (PLC) inhibitor U73122. These pharmacological results are consistent with the involvement of TRP-like channels in mechanosensing by L. polyedra. The TRP channels do not appear to be mechanoreceptors but rather are components of the mechanotransduction signaling pathway and may be activated via a PLC-dependent mechanism. The presence and function of TRP channels in a dinoflagellate emphasize the evolutionary conservation of both the channel structures and their functions.

  12. Fluorescence kinetics of Trp-Trp dipeptide and its derivatives in water via ultrafast fluorescence spectroscopy.

    Science.gov (United States)

    Jia, Menghui; Yi, Hua; Chang, Mengfang; Cao, Xiaodan; Li, Lei; Zhou, Zhongneng; Pan, Haifeng; Chen, Yan; Zhang, Sanjun; Xu, Jianhua

    2015-08-01

    Ultrafast fluorescence dynamics of Tryptophan-Tryptophan (Trp-Trp/Trp2) dipeptide and its derivatives in water have been investigated using a picosecond resolved time correlated single photon counting (TCSPC) apparatus together with a femtosecond resolved upconversion spectrophotofluorometer. The fluorescence decay profiles at multiple wavelengths were fitted by a global analysis technique. Nanosecond fluorescence kinetics of Trp2, N-tert-butyl carbonyl oxygen-N'-aldehyde group-l-tryptophan-l-tryptophan (NBTrp2), l-tryptophan-l-tryptophan methyl ester (Trp2Me), and N-acetyl-l-tryptophan-l-tryptophan methyl ester (NATrp2Me) exhibit multi-exponential decays with the average lifetimes of 1.99, 3.04, 0.72 and 1.22ns, respectively. Due to the intramolecular interaction between two Trp residues, the "water relaxation" lifetime was observed around 4ps, and it is noticed that Trp2 and its derivatives also exhibit a new decay with a lifetime of ∼100ps, while single-Trp fluorescence decay in dipeptides/proteins shows 20-30ps. The intramolecular interaction lifetime constants of Trp2, NBTrp2, Trp2Me and NATrp2Me were then calculated to be 3.64, 0.93, 11.52 and 2.40ns, respectively. Candidate mechanisms (including heterogeneity, solvent relaxation, quasi static self-quenching or ET/PT quenching) have been discussed. Copyright © 2015. Published by Elsevier B.V.

  13. Entrepreneurial Saving Practices and Reinvestment : Theory and Evidence

    NARCIS (Netherlands)

    Beck, T.H.L.; Pamuk, H.; Uras, R.B.

    2014-01-01

    We use a novel enterprise survey from Tanzania to gauge the relationship between saving instruments and entrepreneurial reinvestment. While most informal savings practices do not imply a lower likelihood of entrepreneurial reinvestment when compared with formal savings practices, we find a

  14. Entrepreneurial saving practices and reinvestment : Theory and evidence

    NARCIS (Netherlands)

    Beck, T.H.L.; Pamuk, Haki; Uras, Burak

    2017-01-01

    We use a novel enterprise survey to gauge the relationship between saving instruments and entrepreneurial reinvestment. We show that while most informal saving practices are not associated with a lower likelihood of reinvestment when compared with formal saving practices, there is a significantly

  15. Post-Translational Modifications of TRP Channels

    Directory of Open Access Journals (Sweden)

    Olaf Voolstra

    2014-04-01

    Full Text Available Transient receptor potential (TRP channels constitute an ancient family of cation channels that have been found in many eukaryotic organisms from yeast to human. TRP channels exert a multitude of physiological functions ranging from Ca2+ homeostasis in the kidney to pain reception and vision. These channels are activated by a wide range of stimuli and undergo covalent post-translational modifications that affect and modulate their subcellular targeting, their biophysical properties, or channel gating. These modifications include N-linked glycosylation, protein phosphorylation, and covalent attachment of chemicals that reversibly bind to specific cysteine residues. The latter modification represents an unusual activation mechanism of ligand-gated ion channels that is in contrast to the lock-and-key paradigm of receptor activation by its agonists. In this review, we summarize the post-translational modifications identified on TRP channels and, when available, explain their physiological role.

  16. "TRP inflammation" relationship in cardiovascular system.

    Science.gov (United States)

    Numata, Tomohiro; Takahashi, Kiriko; Inoue, Ryuji

    2016-05-01

    Despite considerable advances in the research and treatment, the precise relationship between inflammation and cardiovascular (CV) disease remains incompletely understood. Therefore, understanding the immunoinflammatory processes underlying the initiation, progression, and exacerbation of many cardiovascular diseases is of prime importance. The innate immune system has an ancient origin and is well conserved across species. Its activation occurs in response to pathogens or tissue injury. Recent studies suggest that altered ionic balance, and production of noxious gaseous mediators link to immune and inflammatory responses with altered ion channel expression and function. Among plausible candidates for this are transient receptor potential (TRP) channels that function as polymodal sensors and scaffolding proteins involved in many physiological and pathological processes. In this review, we will first focus on the relevance of TRP channel to both exogenous and endogenous factors related to innate immune response and transcription factors related to sustained inflammatory status. The emerging role of inflammasome to regulate innate immunity and its possible connection to TRP channels will also be discussed. Secondly, we will discuss about the linkage of TRP channels to inflammatory CV diseases, from a viewpoint of inflammation in a general sense which is not restricted to the innate immunity. These knowledge may serve to provide new insights into the pathogenesis of various inflammatory CV diseases and their novel therapeutic strategies.

  17. Best-Estimates in Bond Markets with Reinvestment Risk

    Directory of Open Access Journals (Sweden)

    Anne MacKay

    2015-07-01

    Full Text Available The concept of best-estimate, prescribed by regulators to value insurance liabilities for accounting and solvency purposes, has recently been discussed extensively in the industry and related academic literature. To differentiate hedgeable and non-hedgeable risks in a general case, recent literature defines best-estimates using orthogonal projections of a claim on the space of replicable payoffs. In this paper, we apply this concept of best-estimate to long-maturity claims in a market with reinvestment risk, since in this case the total liability cannot easily be separated into hedgeable and non-hedgeable parts. We assume that a limited number of short-maturity bonds are traded, and derive the best-estimate price of bonds with longer maturities, thus obtaining a best-estimate yield curve. We therefore use the multifactor Vasiˇcek model and derive within this framework closed-form expressions for the best-estimate prices of long-term bonds.

  18. Urea and Guanidinium Induced Denaturation of a Trp-Cage Miniprotein

    Czech Academy of Sciences Publication Activity Database

    Heyda, Jan; Kožíšek, Milan; Bednárová, Lucie; Thompson, G.; Konvalinka, Jan; Vondrášek, Jiří; Jungwirth, Pavel

    2011-01-01

    Roč. 115, č. 28 (2011), s. 8910-8924 ISSN 1520-6106 R&D Projects: GA MŠk LC512; GA ČR GA203/08/0114 Institutional research plan: CEZ:AV0Z40550506 Keywords : trp-cage denaturation * urea * guanidinium * molecular dynamics Subject RIV: CC - Organic Chemistry Impact factor: 3.696, year: 2011

  19. American Recovery and Reinvestment Act: North Fork Skokomish Powerhouse at Cushman No. 2 Dam

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Steve [DBA Tacoma Power, WA (United States); McCarty, Patrick [DBA Tacoma Power, WA (United States)

    2013-09-30

    The objective of this project was to add generating capacity on an in-stream flow release at Tacoma Power's Cushman hydroelectric project, Cushman No. 2 Dam, FERC Project P-460. The flow that is being used to generate additional electricity was being discharged from a valve at the base of the dam without recovery of the energy. A second objective to the project was to incorporate upstream fish passage by use of a fish collection structure attached to the draft tubes of the hydroelectric units. This will enable reintroduction of native anadromous fish above the dams which have blocked fish passage since the late 1920's. The project was funded in part by the American Recovery and Reinvestment Act through the Department of Energy, Office of Energy, Efficiency and Renewable Energy, Wind and Water Power Program.

  20. Role of TRP channels in the cardiovascular system.

    Science.gov (United States)

    Yue, Zhichao; Xie, Jia; Yu, Albert S; Stock, Jonathan; Du, Jianyang; Yue, Lixia

    2015-02-01

    The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca(2+)-permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca(2+) entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases. Copyright © 2015 the American Physiological Society.

  1. TRP channel functions in the gastrointestinal tract.

    Science.gov (United States)

    Yu, Xiaoyun; Yu, Mingran; Liu, Yingzhe; Yu, Shaoyong

    2016-05-01

    Transient receptor potential (TRP) channels are predominantly distributed in both somatic and visceral sensory nervous systems and play a crucial role in sensory transduction. As the largest visceral organ system, the gastrointestinal (GI) tract frequently accommodates external inputs, which stimulate sensory nerves to initiate and coordinate sensory and motor functions in order to digest and absorb nutrients. Meanwhile, the sensory nerves in the GI tract are also able to detect potential tissue damage by responding to noxious irritants. This nocifensive function is mediated through specific ion channels and receptors expressed in a subpopulation of spinal and vagal afferent nerve called nociceptor. In the last 18 years, our understanding of TRP channel expression and function in GI sensory nervous system has been continuously improved. In this review, we focus on the expressions and functions of TRPV1, TRPA1, and TRPM8 in primary extrinsic afferent nerves innervated in the esophagus, stomach, intestine, and colon and briefly discuss their potential roles in relevant GI disorders.

  2. Opportunistic activation of TRP receptors by endogenous lipids: exploiting lipidomics to understand TRP receptor cellular communication.

    Science.gov (United States)

    Bradshaw, Heather B; Raboune, Siham; Hollis, Jennifer L

    2013-03-19

    Transient receptor potential channels (TRPs) form a large family of ubiquitous non-selective cation channels that function as cellular sensors and in many cases regulate intracellular calcium. Identification of the endogenous ligands that activate these TRP receptors is still under intense investigation with the majority of these channels still remaining "orphans." That these channels respond to a variety of external stimuli (e.g. plant-derived lipids, changes in temperature, and changes in pH) provides a framework for their abilities as cellular sensors, however, the mechanism of direct activation is still under much debate and research. In the cases where endogenous ligands (predominately lipids) have shown direct activation of a channel, multiple ligands have been shown to activate the same channel suggesting that these receptors are "promiscuous" in nature. Lipidomics of a growing class of endogenous lipids, N-acyl amides, the most famous of which is N-arachidonoyl ethanolamine (the endogenous cannabinoid, Anandamide) is providing a novel set of ligands that have been shown to activate some members of the TRP family and have the potential to deorphanize many more. Here it is argued that activation of TRPV receptors, a subset of the larger family of TRPs, by multiple endogenous lipids that are structurally analogous is a model system to drive our understanding that many TRP receptors are not promiscuous, but are more characteristically "opportunistic" in nature; exploiting the structural similarity and biosynthesis of a narrow range of analogous endogenous lipids. In addition, this manuscript will compare the activation properties of TRPC5 to the activity profile of an "orphan" lipid, N-palmitoyl glycine; further demonstrating that lipidomics aimed at expanding our knowledge of the family of N-acyl amides has the potential to provide novel avenues of research for TRP receptors. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. White House Technology Reinvestment Project Briefing And Transcripts

    Science.gov (United States)

    1993-04-12

    product and making it in Malaysia and your participation in phase one and not providing U.S. jobs. That’s number phase two. But the technical risk is as...29CFR 1910 120 OSHA (inaudible). And DR. KRAMER: I think you have to be we do a lot of retraining for a little careful in the environmental people

  4. Technology Reinvestment Project Manufacturing Education and Training. Volume 1

    Science.gov (United States)

    Schroer, Bernard J.; Bond, Arthur J.

    1997-01-01

    The manufacturing education program is a joint program between the University of Alabama in Huntsville's (UAH) College of Engineering and Alabama A&M University's (AAMLJ) School of Engineering and Technology. The objective of the program is to provide more hands-on experiences to undergraduate engineering and engineering technology students. The scope of work consisted of. Year 1, Task 1: Review courses at Alabama Industrial Development Training (AIDT); Task 2: Review courses at UAH and AAMU; Task 3: Develop new lab manuals; Task 4: Field test manuals; Task 5: Prepare annual report. Year 2, Task 1: Incorporate feedback into lab manuals; Task 2 : Introduce lab manuals into classes; Task 3: Field test manuals; Task 4: Prepare annual report. Year 3, Task 1: Incorporate feedback into lab manuals; Task 2: Introduce lab manuals into remaining classes; Task 3: Conduct evaluation with assistance of industry; Task 4: Prepare final report. This report only summarizes the activities of the University of Alabama in Huntsville. The activities of Alabama A&M University are contained in a separate report.

  5. Evolutionary conservation and changes in insect TRP channels

    OpenAIRE

    Tominaga Makoto; Kohno Keigo; Sokabe Takaaki; Matsuura Hironori; Kadowaki Tatsuhiko

    2009-01-01

    Abstract Background TRP (Transient Receptor Potential) channels respond to diverse stimuli and thus function as the primary integrators of varied sensory information. They are also activated by various compounds and secondary messengers to mediate cell-cell interactions as well as to detect changes in the local environment. Their physiological roles have been primarily characterized only in mice and fruit flies, and evolutionary studies are limited. To understand the evolution of insect TRP c...

  6. Characterization of two trpE genes encoding anthranilate synthase α-subunit in Azospirillum brasilense

    International Nuclear Information System (INIS)

    Ge Shimei; Xie Baoen; Chen Sanfeng

    2006-01-01

    The previous report from our laboratory has recently identified a new trpE gene (termed trpE 2 ) which exists independently in Azospirillum brasilense Yu62. In this study, amplification of trpE(G) (termed trpE 1 (G) here) confirmed that there are two copies of trpE gene, one trpE being fused into trpG while the other trpE existed independently. This is First report to suggest that two copies of the trpE gene exist in this bacterium. Comparison of the nucleotide sequence demonstrated that putative leader peptide, terminator, and anti-terminator were found upstream of trpE 1 (G) while these sequence features did not exist in front of trpE 2 . The β-galactosidase activity of an A. brasilense strain carrying a trpE 2 -lacZ fusion remained constant at different tryptophan concentrations, but the β-galactosidase activity of the same strain carrying a trpE 1 (G)-lacZ fusion decreased as the tryptophan concentration increased. These data suggest that the expression of trpE 1 (G) is regulated at the transcriptional level by attenuation while trpE 2 is constantly expressed. The anthranilate synthase assays with trpE 1 (G) - and trpE 2 - mutants demonstrated that TrpE 1 (G) fusion protein is feedback inhibited by tryptophan while TrpE 2 protein is not. We also found that both trpE 1 (G) and trpE 2 gene products were involved in IAA synthesis

  7. Are Trp53 rescue of Brca1 embryonic lethality and Trp53/Brca1 breast cancer association related?

    International Nuclear Information System (INIS)

    McAllister, Kimberly A; Wiseman, Roger W

    2002-01-01

    Brca1 is involved in multiple biological pathways including DNA damage repair, transcriptional regulation, and cell-cycle progression. A complex pattern of interactions of Brca1 with Trp53 has also emerged. Xu and coworkers found that haploid loss of Trp53 significantly reduces the embryonic lethality observed in mice with a homozygous in-frame deletion of Brca1 exon 11. They report that widespread apoptosis correlates with the embryonic lethality resulting from this homozygous Δ11 Brca1 mutation. A mechanism responsible for Brca1-associated carcinogenesis is proposed. These experiments extend our knowledge of a complex Brca1/Trp53 relationship. However, the precise mechanisms through which Brca1 interacts with Trp53 to suppress mammary tumor formation have yet to be elucidated

  8. 12 CFR 303.5 - Effect of Community Reinvestment Act performance on filings.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Effect of Community Reinvestment Act performance on filings. 303.5 Section 303.5 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE... Reinvestment Act performance on filings. Among other factors, the FDIC takes into account the record of...

  9. 77 FR 17456 - Buy American Exception Under the American Recovery and Reinvestment Act of 2009

    Science.gov (United States)

    2012-03-26

    ...-2138-01] Buy American Exception Under the American Recovery and Reinvestment Act of 2009 AGENCY... exception to the Buy American Provisions of the American Recovery and Reinvestment Act of 2009 (ARRA or... future years on electricity. The contract specifications required that all exterior photovoltaic...

  10. Network investments, reinvestments, maintenance[3 figs.]; Nettinvesteringer, reinvesteringer, vedlikehold

    Energy Technology Data Exchange (ETDEWEB)

    Sand, Kjell; Solvang, Eivind; Lundgaard, Lars

    2003-07-01

    Following the deregulation of the electricity sector in 1991, the general trend has been a growing cost and cost-benefit awareness in all parts of the sector. In the network activities, the companies are currently focusing sharply on cutting costs in the monopoly franchise and at the same time trying to establish new activity outside the revenue limit. Several polls and analyses conducted by SINTEF Energy show that the network companies are strongly influenced by the regulation enforced by NVE (The Norwegian Water Resources and Energy Directorate). This is true of investments, reinvestments and maintenance.

  11. Evolutionary conservation and changes in insect TRP channels.

    Science.gov (United States)

    Matsuura, Hironori; Sokabe, Takaaki; Kohno, Keigo; Tominaga, Makoto; Kadowaki, Tatsuhiko

    2009-09-10

    TRP (Transient Receptor Potential) channels respond to diverse stimuli and thus function as the primary integrators of varied sensory information. They are also activated by various compounds and secondary messengers to mediate cell-cell interactions as well as to detect changes in the local environment. Their physiological roles have been primarily characterized only in mice and fruit flies, and evolutionary studies are limited. To understand the evolution of insect TRP channels and the mechanisms of integrating sensory inputs in insects, we have identified and compared TRP channel genes in Drosophila melanogaster, Bombyx mori, Tribolium castaneum, Apis mellifera, Nasonia vitripennis, and Pediculus humanus genomes as part of genome sequencing efforts. All the insects examined have 2 TRPV, 1 TRPN, 1 TRPM, 3 TRPC, and 1 TRPML subfamily members, demonstrating that these channels have the ancient origins in insects. The common pattern also suggests that the mechanisms for detecting mechanical and visual stimuli and maintaining lysosomal functions may be evolutionarily well conserved in insects. However, a TRPP channel, the most ancient TRP channel, is missing in B. mori, A. mellifera, and N. vitripennis. Although P. humanus and D. melanogaster contain 4 TRPA subfamily members, the other insects have 5 TRPA subfamily members. T. castaneum, A. mellifera, and N. vitripennis contain TRPA5 channels, which have been specifically retained or gained in Coleoptera and Hymenoptera. Furthermore, TRPA1, which functions for thermotaxis in Drosophila, is missing in A. mellifera and N. vitripennis; however, they have other Hymenoptera-specific TRPA channels (AmHsTRPA and NvHsTRPA). NvHsTRPA expressed in HEK293 cells is activated by temperature increase, demonstrating that HsTRPAs function as novel thermal sensors in Hymenoptera. The total number of insect TRP family members is 13-14, approximately half that of mammalian TRP family members. As shown for mammalian TRP channels, this

  12. Evolutionary conservation and changes in insect TRP channels

    Directory of Open Access Journals (Sweden)

    Tominaga Makoto

    2009-09-01

    Full Text Available Abstract Background TRP (Transient Receptor Potential channels respond to diverse stimuli and thus function as the primary integrators of varied sensory information. They are also activated by various compounds and secondary messengers to mediate cell-cell interactions as well as to detect changes in the local environment. Their physiological roles have been primarily characterized only in mice and fruit flies, and evolutionary studies are limited. To understand the evolution of insect TRP channels and the mechanisms of integrating sensory inputs in insects, we have identified and compared TRP channel genes in Drosophila melanogaster, Bombyx mori, Tribolium castaneum, Apis mellifera, Nasonia vitripennis, and Pediculus humanus genomes as part of genome sequencing efforts. Results All the insects examined have 2 TRPV, 1 TRPN, 1 TRPM, 3 TRPC, and 1 TRPML subfamily members, demonstrating that these channels have the ancient origins in insects. The common pattern also suggests that the mechanisms for detecting mechanical and visual stimuli and maintaining lysosomal functions may be evolutionarily well conserved in insects. However, a TRPP channel, the most ancient TRP channel, is missing in B. mori, A. mellifera, and N. vitripennis. Although P. humanus and D. melanogaster contain 4 TRPA subfamily members, the other insects have 5 TRPA subfamily members. T. castaneum, A. mellifera, and N. vitripennis contain TRPA5 channels, which have been specifically retained or gained in Coleoptera and Hymenoptera. Furthermore, TRPA1, which functions for thermotaxis in Drosophila, is missing in A. mellifera and N. vitripennis; however, they have other Hymenoptera-specific TRPA channels (AmHsTRPA and NvHsTRPA. NvHsTRPA expressed in HEK293 cells is activated by temperature increase, demonstrating that HsTRPAs function as novel thermal sensors in Hymenoptera. Conclusion The total number of insect TRP family members is 13-14, approximately half that of mammalian TRP

  13. Development of Chemically Defined Media to Express Trp-Analog-Labeled Proteins in a Lactococcus lactis Trp Auxotroph.

    Science.gov (United States)

    Shao, Jinfeng; Marcondes, Marcelo F M; Oliveira, Vitor; Broos, Jaap

    2016-01-01

    Chemically defined media for growth of Lactococcus lactis strains contain about 50 components, making them laborious and expensive growth media. However, they are crucial for metabolism studies as well as for expression of heterologous proteins labeled with unnatural amino acids. In particular, the L. lactis Trp auxotroph PA1002, overexpressing the tryptophanyl tRNA synthetase enzyme of L. lactis, is very suitable for the biosynthetic incorporation of Trp analogs in proteins because of its most relaxed substrate specificity reported towards Trp analogs. Here we present two much simpler defined media for L. lactis, which consist of only 24 or 31 components, respectively, and with which the L. lactis Trp auxotroph shows similar growth characteristics as with a 50-component chemically defined medium. Importantly, the expression levels of two recombinant proteins used for evaluation were up to 2-3 times higher in these new media than in the 50-component medium, without affecting the Trp analog incorporation efficiency. Taken together, the simplest chemically defined media reported so far for L. lactis are presented. Since L. lactis also shows auxotrophy for Arg, His, Ile, Leu Val, and Met, our simplified media may also be useful for the biosynthetic incorporation of analogs of these five amino acids. © 2016 The Author(s) Published by S. Karger AG, Basel.

  14. Sub-cellular distribution and translocation of TRP channels.

    Science.gov (United States)

    Toro, Carlos A; Arias, Luis A; Brauchi, Sebastian

    2011-01-01

    Cellular electrical activity is the result of a highly complex processes that involve the activation of ion channel proteins. Ion channels make pores on cell membranes that rapidly transit between conductive and non-conductive states, allowing different ions to flow down their electrochemical gradients across cell membranes. In the case of neuronal cells, ion channel activity orchestrates action potentials traveling through axons, enabling electrical communication between cells in distant parts of the body. Somatic sensation -our ability to feel touch, temperature and noxious stimuli- require ion channels able to sense and respond to our peripheral environment. Sensory integration involves the summing of various environmental cues and their conversion into electrical signals. Members of the Transient Receptor Potential (TRP) family of ion channels have emerged as important mediators of both cellular sensing and sensory integration. The regulation of the spatial and temporal distribution of membrane receptors is recognized as an important mechanism for controlling the magnitude of the cellular response and the time scale on which cellular signaling occurs. Several studies have shown that this mechanism is also used by TRP channels to modulate cellular response and ultimately fulfill their physiological function as sensors. However, the inner-working of this mode of control for TRP channels remains poorly understood. The question of whether TRPs intrinsically regulate their own vesicular trafficking or weather the dynamic regulation of TRP channel residence on the cell surface is caused by extrinsic changes in the rates of vesicle insertion or retrieval remain open. This review will examine the evidence that sub-cellular redistribution of TRP channels plays an important role in regulating their activity and explore the mechanisms that control the trafficking of vesicles containing TRP channels.

  15. Stimulation of Drosophila TrpL by capacitative Ca2+ entry.

    OpenAIRE

    Estacion, M; Sinkins, W G; Schilling, W P

    1999-01-01

    Trp-like protein (TrpL, where Trp is transient receptor-potential protein) of Drosophila, a non-selective cation channel activated in photoreceptor cells by a phospholipase C-dependent mechanism, is thought to be a prototypical receptor-activated channel. Our previous studies showed that TrpL channels are not activated by depletion of internal Ca2+ stores when expressed in Sf9 cells. Using fura-2 to measure cation influx via TrpL, and cell-attached patch recordings to monitor TrpL single-chan...

  16. TRP Channels as Therapeutic Targets in Diabetes and Obesity

    Directory of Open Access Journals (Sweden)

    Andrea Zsombok

    2016-08-01

    Full Text Available During the last three to four decades the prevalence of obesity and diabetes mellitus has greatly increased worldwide, including in the United States. Both the short- and long-term forecasts predict serious consequences for the near future, and encourage the development of solutions for the prevention and management of obesity and diabetes mellitus. Transient receptor potential (TRP channels were identified in tissues and organs important for the control of whole body metabolism. A variety of TRP channels has been shown to play a role in the regulation of hormone release, energy expenditure, pancreatic function, and neurotransmitter release in control, obese and/or diabetic conditions. Moreover, dietary supplementation of natural ligands of TRP channels has been shown to have potential beneficial effects in obese and diabetic conditions. These findings raised the interest and likelihood for potential drug development. In this mini-review, we discuss possibilities for better management of obesity and diabetes mellitus based on TRP-dependent mechanisms.

  17. A risk based model supporting long term maintenance and reinvestment strategy decision making

    Energy Technology Data Exchange (ETDEWEB)

    Sand, Kjell; Montard, Julien; Tremoen, Tord H.

    2010-02-15

    This Technical Report is a product from the project Risk-Based Distribution System Asset Management (short: RISK DSAM) - Work Package 3 Risk exposure on company/strategic level. In the report a concept for portfolio distribution system asset management is presented. The approach comprises four main steps: 1. Decide the asset base. 2. Divide the asset base into relevant archetypes. 3. Develop or select relevant maintenance and reinvestment strategies for the different archetypes. 4. Estimate risks and costs for each archetype for the relevant strategies. For the different steps guidelines are given and a proposal for implementation of the concept is given in terms of a proposed IT system architecture.To evaluate the feasibility of such a concept, a prototype was developed in by using Visual Basic macros in Excel using real technical data from a small DSO. The experience from using the prototype shows that the concept is realistic. All assets are included and depending of the ambition of the risk analysis both simple simulation models and more advanced might be embedded. Presentations of the concept for a utility engineers have receive positive feedback indicating that the concept is regarded as a practical way to develop risk based asset management strategies for the asset fleet. It should be noted that the concept should be applied on a company strategic level and is thus not designed to be applied for a specific project or asset decisions. For this, more detailed models with area specific information, topology etc. are needed. (Author)

  18. American Recovery and Reinvestment Act-comparative effectiveness research infrastructure investments: emerging data resources, tools and publications.

    Science.gov (United States)

    Segal, Courtney; Holve, Erin

    2014-11-01

    The Recovery Act provided a substantial, one-time investment in data infrastructure for comparative effectiveness research (CER). A review of the publications, data, and tools developed as a result of this support has informed understanding of the level of effort undertaken by these projects. Structured search queries, as well as outreach efforts, were conducted to identify and review resources from American Recovery and Reinvestment Act of 2009 CER projects building electronic clinical data infrastructure. The findings from this study provide a spectrum of productivity across a range of topics and settings. A total of 451 manuscripts published in 192 journals, and 141 data resources and tools were identified and address gaps in evidence on priority populations, conditions, and the infrastructure needed to support CER.

  19. Is TrpM5 a reliable marker for chemosensory cells? Multiple types of microvillous cells in the main olfactory epithelium of mice

    Directory of Open Access Journals (Sweden)

    Finger Thomas E

    2008-12-01

    Full Text Available Abstract Background In the past, ciliated receptor neurons, basal cells, and supporting cells were considered the principal components of the main olfactory epithelium. Several studies reported the presence of microvillous cells but their function is unknown. A recent report showed cells in the main olfactory epithelium that express the transient receptor potential channel TrpM5 claiming that these cells are chemosensory and that TrpM5 is an intrinsic signaling component of mammalian chemosensory organs. We asked whether the TrpM5-positive cells in the olfactory epithelium are microvillous and whether they belong to a chemosensory system, i.e. are olfactory neurons or trigeminally-innervated solitary chemosensory cells. Results We investigated the main olfactory epithelium of mice at the light and electron microscopic level and describe several subpopulations of microvillous cells. The ultrastructure of the microvillous cells reveals at least three morphologically different types two of which express the TrpM5 channel. None of these cells have an axon that projects to the olfactory bulb. Tests with a large panel of cell markers indicate that the TrpM5-positive cells are not sensory since they express neither neuronal markers nor are contacted by trigeminal nerve fibers. Conclusion We conclude that TrpM5 is not a reliable marker for chemosensory cells. The TrpM5-positive cells of the olfactory epithelium are microvillous and may be chemoresponsive albeit not part of the sensory apparatus. Activity of these microvillous cells may however influence functionality of local elements of the olfactory system.

  20. Broad-range TRP channel inhibitors (2-APB, flufenamic acid, SKF-96365) affect differently contraction of resistance and conduit femoral arteries of rat

    Czech Academy of Sciences Publication Activity Database

    Bencze, Michal; Behuliak, Michal; Vavřínová, Anna; Zicha, Josef

    2015-01-01

    Roč. 765, Oct 15 (2015), s. 533-540 ISSN 0014-2999 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : femoral artery * TRP channel * 2-APB * flufenamic acid * SKF-96365 * vascular contraction Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.730, year: 2015

  1. Aging based maintenance and reinvestment scheduling of electric distribution

    Energy Technology Data Exchange (ETDEWEB)

    Korpijarvi, J.

    2012-07-01

    The maintenance of electric distribution network is a topical question for distribution system operators because of increasing significance of failure costs. In this dissertation the maintenance practices of the distribution system operators are analyzed and a theory for scheduling maintenance activities and reinvestment of distribution components is created. The scheduling is based on the deterioration of components and the increasing failure rates due to aging. The dynamic programming algorithm is used as a solving method to maintenance problem which is caused by the increasing failure rates of the network. The other impacts of network maintenance like environmental and regulation reasons are not included to the scope of this thesis. Further the tree trimming of the corridors and the major disturbance of the network are not included to the problem optimized in this thesis. For optimizing, four dynamic programming models are presented and the models are tested. Programming is made in VBA-language to the computer. For testing two different kinds of test networks are used. Because electric distribution system operators want to operate with bigger component groups, optimal timing for component groups is also analyzed. A maintenance software package is created to apply the presented theories in practice. An overview of the program is presented (orig.)

  2. The transient receptor potential, TRP4, cation channel is a novel member of the family of calmodulin binding proteins.

    OpenAIRE

    Trost, C; Bergs, C; Himmerkus, N; Flockerzi, V

    2001-01-01

    The mammalian gene products, transient receptor potential (trp)1 to trp7, are related to the Drosophila TRP and TRP-like ion channels, and are candidate proteins underlying agonist-activated Ca(2+)-permeable ion channels. Recently, the TRP4 protein has been shown to be part of native store-operated Ca(2+)-permeable channels. These channels, most likely, are composed of other proteins in addition to TRP4. In the present paper we report the direct interaction of TRP4 and calmodulin (CaM) by: (1...

  3. Expression of the benign HEXA mutations, Arg247Trp and Arg249Trp, associated with beta-hexosaminidase A pseudodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Z.; Petroulakis, E.; Salo, T. [Univ. of Manitoba (Canada)] [and others

    1994-09-01

    {beta}-Hexosaminidase (Hex A) is a heterodimer of {alpha} and {beta} subunits encoded by the HEXA and HEXB genes, respectively. Mutations in the HEXA gene typically cause Tay-Sachs disease or less severe forms of G{sub M2} gangliosidosis. However, two benign mutations (Arg247Trp and Arg249Trp) in the {alpha}-subunit of Hex A account for Hex A deficiency in {approximately}36% of non-Jewish enzyme-defined Tay-Sachs disease carriers. These mutations do not result in any apparent clinical phenotype in individuals who are genetic compounds with a second disease-causing mutation. We expressed the {alpha}-subunit harboring each of the benign mutations separately to study activity toward the synthetic substrate, 4-MUGS, for comparison to activity from enzymes containing mutations associated with other forms of G{sub M2} gangliosidosis. The C739T (Arg247Trp;benign), C745T (Arg 249Trp; benign), G805A (Gly269Ser; adult-onset), G749A (Gly250Asp; juvenile), and C508T (Arg170Trp; infantile) mutations were introduced into the {alpha}-subunit cDNA. These were transfected alone, or with the {beta}-subunit cDNA, to generate Hex S ({alpha}{alpha}) or Hex A ({alpha}{beta}), respectively. The activities were monitored using 4-MUGS, and the levels of {alpha}-subunit protein were assessed by Western blotting. Repeated experiments show that the benign mutations produce approximately 35% of normal Hex S and 40% of normal Hex A activity. This level is much higher than that of Hex A harbouring the Gly169Ser adult-onset mutation (12%). A sequential decrease in expressed Hex A activity is observed as mutations associated with more severe phenotypes are expressed. The benign mutations also result in lower levels of mature {alpha}-subunit protein compared to normal, and slightly reduced levels of {alpha}-subunit precursor protein. The Hex A deficiency resulting from benign mutations is not as great as that associated with disease-causing mutations.

  4. Trp-cage: Folding free energy landscape in explicit water

    Science.gov (United States)

    Zhou, Ruhong

    2003-11-01

    Trp-cage is a 20-residue miniprotein, which is believed to be the fastest folder known so far. In this study, the folding free energy landscape of Trp-cage has been explored in explicit solvent by using an OPLSAA force field with periodic boundary condition. A highly parallel replica exchange molecular dynamics method is used for the conformation space sampling, with the help of a recently developed efficient molecular dynamics algorithm P3ME/RESPA (particle-particle particle-mesh Ewald/reference system propagator algorithm). A two-step folding mechanism is proposed that involves an intermediate state where two correctly formed partial hydrophobic cores are separated by an essential salt-bridge between residues Asp-9 and Arg-16 near the center of the peptide. This metastable intermediate state provides an explanation for the superfast folding process. The free energy landscape is found to be rugged at low temperatures, and then becomes smooth and funnel-like above 340 K. The lowest free energy structure at 300 K is only 1.50 Å C-RMSD (C-rms deviation) from the NMR structures. The simulated nuclear Overhauser effect pair distances are in excellent agreement with the raw NMR data. The temperature dependence of the Trp-cage population, however, is found to be significantly different from experiment, with a much higher melting transition temperature above 400 K (experimental 315 K), indicating that the current force fields, parameterized at room temperature, need to be improved to correctly predict the temperature dependence.

  5. Modulation of TRP channels by resveratrol and other stilbenoids

    Directory of Open Access Journals (Sweden)

    Yu Lina

    2013-02-01

    Full Text Available Abstract Background Resveratrol (3,5,4’ - trihydroxy-trans-stilbene, a widely distributed natural stilbenoid, was proposed to account for the unique effects of red wine on life span and health. It has been reported to possess various biological and pharmacological activities, such as anti-oxidant, anti-inflammatory, and anti-carcinogenic effects. Here, using whole-cell patch-clamp techniques and behavioral analyses, we investigated whether resveratrol and other stilbenoids can modulate TRP channels in sensory neurons in vitro, and have analgesic effects in vivo. Results We found that resveratrol dose-dependently suppressed the allyl isothiocyanate (AITC-induced currents (IAITC in HEK293 cells that express TRPA1, as well as in rat dorsal root ganglion (DRG neurons. Instead, pinosylvin methyl ether (PME, another derivate of stilbene which has a similar structure to resveratrol, dose-dependently blocked the capsaicin-induced currents (ICAP in HEK293 cells that express TRPV1 as well as in DRG neurons. Interestingly, resveratrol had no inhibitory effect on the ICAP, and PME had no effect on the IAITC. Otherwise, trans-stilbene showed no any effect on IAITC or ICAP. The concentration response curve of AITC showed that resveratrol inhibited the action of TRPA1 not by changing the EC50, but by suppressing the AITC-induced maximum response. By contrast, the inhibition of TRPV1 by PME did not change the capsaicin-induced maximum response but did cause a right shift of the EC50. Moreover, pre-administration of resveratrol suppressed intraplantar injections of AITC-evoked nocifensive behaviors, as well as that PME suppressed capsaicin-evoked one. Conclusions These data suggest that resveratrol and other stilbenoids may have an inhibitory effect on TRP channels. In addition, these stilbenoids modulate TRP channel activity in different ways.

  6. 75 FR 16498 - Buy American Exceptions Under the American Recovery and Reinvestment Act of 2009

    Science.gov (United States)

    2010-04-01

    ... Reinvestment Act of 2009 (Pub. L. 111-05, approved February 17, 2009) (Recovery Act), and implementing guidance... stalls at the River Terrace Senior Apartments. FOR FURTHER INFORMATION CONTACT: Dominique G. Blom, Deputy... the Recovery Act and OMB's implementing guidance published on April 23, 2009 (74 FR 18449), this...

  7. 75 FR 69453 - Buy American Exceptions Under the American Recovery and Reinvestment Act of 2009

    Science.gov (United States)

    2010-11-12

    ... Reinvestment Act of 2009 (Pub. L. 111-05, approved February 17, 2009) (Recovery Act), and implementing guidance... conditioning units and Ground Fault Circuit Interrupter (GFCI) outlets for the Riverdale Senior Apartments... implementing guidance published on April 23, 2009 (74 FR 18449), this notice advises the public that, on...

  8. Why the Community Reinvestment Act cannot be blamed for the subprime crisis

    NARCIS (Netherlands)

    Aalbers, M.B.

    2009-01-01

    It has become common practice—and in particular, but not exclusively, in conservative media—to blame the Community Reinvestment Act (CRA) of 1977 for the U.S. subprime mortgage and foreclosure crisis that triggered the global financial crisis. It is argued that the CRA forced lenders to give

  9. 76 FR 24043 - Buy American Exceptions Under the American Recovery and Reinvestment Act of 2009

    Science.gov (United States)

    2011-04-29

    ... Minneapolis Public Housing Authority for the purchase and installation of compact fluorescent lamps (CFLs) and... Under the American Recovery and Reinvestment Act of 2009 AGENCY: Office of the Assistant Secretary for Public and Indian Housing, HUD. ACTION: Notice. SUMMARY: In accordance with the American Recovery and...

  10. 31 CFR 353.64 - Payment, reinvestment, or exchange-voluntary guardian of an incapacitated person.

    Science.gov (United States)

    2010-07-01

    ...-voluntary guardian of an incapacitated person. 353.64 Section 353.64 Money and Finance: Treasury Regulations..., Incompetents, Aged Persons, Absentees, et al. § 353.64 Payment, reinvestment, or exchange—voluntary guardian of... recognition as voluntary guardian for the purpose of redeeming the owner's bonds, if the total redemption...

  11. Investing American Recovery and Reinvestment Act Funds to Advance Capability, Reliability, and Performance in NASA Wind Tunnels

    Science.gov (United States)

    Sydnor, Goerge H.

    2010-01-01

    The National Aeronautics and Space Administration's (NASA) Aeronautics Test Program (ATP) is implementing five significant ground-based test facility projects across the nation with funding provided by the American Recovery and Reinvestment Act (ARRA). The projects were selected as the best candidates within the constraints of the ARRA and the strategic plan of ATP. They are a combination of much-needed large scale maintenance, reliability, and system upgrades plus creating new test beds for upcoming research programs. The projects are: 1.) Re-activation of a large compressor to provide a second source for compressed air and vacuum to the Unitary Plan Wind Tunnel at the Ames Research Center (ARC) 2.) Addition of high-altitude ice crystal generation at the Glenn Research Center Propulsion Systems Laboratory Test Cell 3, 3.) New refrigeration system and tunnel heat exchanger for the Icing Research Tunnel at the Glenn Research Center, 4.) Technical viability improvements for the National Transonic Facility at the Langley Research Center, and 5.) Modifications to conduct Environmentally Responsible Aviation and Rotorcraft research at the 14 x 22 Subsonic Tunnel at Langley Research Center. The selection rationale, problem statement, and technical solution summary for each project is given here. The benefits and challenges of the ARRA funded projects are discussed. Indirectly, this opportunity provides the advantages of developing experience in NASA's workforce in large projects and maintaining corporate knowledge in that very unique capability. It is envisioned that improved facilities will attract a larger user base and capabilities that are needed for current and future research efforts will offer revenue growth and future operations stability. Several of the chosen projects will maximize wind tunnel reliability and maintainability by using newer, proven technologies in place of older and obsolete equipment and processes. The projects will meet NASA's goal of

  12. Significance of the Centrally Expressed TRP Channel "Painless" in "Drosophila" Courtship Memory

    Science.gov (United States)

    Sakai, Takaomi; Sato, Shoma; Ishimoto, Hiroshi; Kitamoto, Toshihiro

    2013-01-01

    Considerable evidence has demonstrated that transient receptor potential (TRP) channels play vital roles in sensory neurons, mediating responses to various environmental stimuli. In contrast, relatively little is known about how TRP channels exert their effects in the central nervous system to control complex behaviors. This is also true for the…

  13. A polycystin-type transient receptor potential (Trp channel that is activated by ATP

    Directory of Open Access Journals (Sweden)

    David Traynor

    2017-02-01

    Full Text Available ATP and ADP are ancient extra-cellular signalling molecules that in Dictyostelium amoebae cause rapid, transient increases in cytosolic calcium due to an influx through the plasma membrane. This response is independent of hetero-trimeric G-proteins, the putative IP3 receptor IplA and all P2X channels. We show, unexpectedly, that it is abolished in mutants of the polycystin-type transient receptor potential channel, TrpP. Responses to the chemoattractants cyclic-AMP and folic acid are unaffected in TrpP mutants. We report that the DIF morphogens, cyclic-di-GMP, GABA, glutamate and adenosine all induce strong cytoplasmic calcium responses, likewise independently of TrpP. Thus, TrpP is dedicated to purinergic signalling. ATP treatment causes cell blebbing within seconds but this does not require TrpP, implicating a separate purinergic receptor. We could detect no effect of ATP on chemotaxis and TrpP mutants grow, chemotax and develop almost normally in standard conditions. No gating ligand is known for the human homologue of TrpP, polycystin-2, which causes polycystic kidney disease. Our results now show that TrpP mediates purinergic signalling in Dictyostelium and is directly or indirectly gated by ATP.

  14. Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies

    Directory of Open Access Journals (Sweden)

    Aaron D. Mickle

    2016-11-01

    Full Text Available Specialized receptors belonging to the transient receptor potential (TRP family of ligand-gated ion channels constitute the critical detectors and transducers of pain-causing stimuli. Nociceptive TRP channels are predominantly expressed by distinct subsets of sensory neurons of the peripheral nervous system. Several of these TRP channels are also expressed in neurons of the central nervous system, and in non-neuronal cells that communicate with sensory nerves. Nociceptive TRPs are activated by specific physico-chemical stimuli to provide the excitatory trigger in neurons. In addition, decades of research has identified a large number of immune and neuromodulators as mediators of nociceptive TRP channel activation during injury, inflammatory and other pathological conditions. These findings have led to aggressive targeting of TRP channels for the development of new-generation analgesics. This review summarizes the complex activation and/or modulation of nociceptive TRP channels under pathophysiological conditions, and how these changes underlie acute and chronic pain conditions. Furthermore, development of small-molecule antagonists for several TRP channels as analgesics, and the positive and negative outcomes of these drugs in clinical trials are discussed. Understanding the diverse functional and modulatory properties of nociceptive TRP channels is critical to function-based drug targeting for the development of evidence-based and efficacious new generation analgesics.

  15. Chemical Excitation and Inactivation in Photoreceptors of the Fly Mutants trp and nss

    NARCIS (Netherlands)

    Suss, E.; Barash, S.; Stavenga, D.G.; Stieve, H.; Selinger, Z.; Minke, B.

    1989-01-01

    The Drosophila and Lucilia photoreceptor mutants, trp and nss, respond like wild-type flies to a short pulse of intense light or prolonged dim light; however, upon continuous intense illumination, the trp and nss mutants are unable to maintain persistent excitation. This defect manifests itself by a

  16. Nonlinear vs. linear biasing in Trp-cage folding simulations

    Energy Technology Data Exchange (ETDEWEB)

    Spiwok, Vojtěch, E-mail: spiwokv@vscht.cz; Oborský, Pavel; Králová, Blanka [Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Technická 3, Prague 6 166 28 (Czech Republic); Pazúriková, Jana [Institute of Computer Science, Masaryk University, Botanická 554/68a, 602 00 Brno (Czech Republic); Křenek, Aleš [Institute of Computer Science, Masaryk University, Botanická 554/68a, 602 00 Brno (Czech Republic); Center CERIT-SC, Masaryk Univerzity, Šumavská 416/15, 602 00 Brno (Czech Republic)

    2015-03-21

    Biased simulations have great potential for the study of slow processes, including protein folding. Atomic motions in molecules are nonlinear, which suggests that simulations with enhanced sampling of collective motions traced by nonlinear dimensionality reduction methods may perform better than linear ones. In this study, we compare an unbiased folding simulation of the Trp-cage miniprotein with metadynamics simulations using both linear (principle component analysis) and nonlinear (Isomap) low dimensional embeddings as collective variables. Folding of the mini-protein was successfully simulated in 200 ns simulation with linear biasing and non-linear motion biasing. The folded state was correctly predicted as the free energy minimum in both simulations. We found that the advantage of linear motion biasing is that it can sample a larger conformational space, whereas the advantage of nonlinear motion biasing lies in slightly better resolution of the resulting free energy surface. In terms of sampling efficiency, both methods are comparable.

  17. Application of amphipols for structure-functional analysis of TRP channels.

    Science.gov (United States)

    Huynh, Kevin W; Cohen, Matthew R; Moiseenkova-Bell, Vera Y

    2014-10-01

    Amphipathic polymers (amphipols), such as A8-35 and SApol, are a new tool for stabilizing integral membrane proteins in detergent-free conditions for structural and functional studies. Transient receptor potential (TRP) ion channels function as tetrameric protein complexes in a diverse range of cellular processes including sensory transduction. Mammalian TRP channels share ~20 % sequence similarity and are categorized into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPA (ankyrin), TRPM (melastatin), TRPP (polycystin), and TRPML (mucolipin). Due to the inherent difficulties in purifying eukaryotic membrane proteins, structural studies of TRP channels have been limited. Recently, A8-35 was essential in resolving the molecular architecture of the nociceptor TRPA1 and led to the determination of a high-resolution structure of the thermosensitive TRPV1 channel by cryo-EM. Newly developed maltose-neopentyl glycol (MNG) detergents have also proven to be useful in stabilizing TRP channels for structural analysis. In this review, we will discuss the impacts of amphipols and MNG detergents on structural studies of TRP channels by cryo-EM. We will compare how A8-35 and MNG detergents interact with the hydrophobic transmembrane domains of TRP channels. In addition, we will discuss what these cryo-EM studies reveal on the importance of screening different types of surfactants toward determining high-resolution structures of TRP channels.

  18. A structural view of ligand-dependent activation in thermoTRP channels

    Directory of Open Access Journals (Sweden)

    Ximena eSteinberg

    2014-05-01

    Full Text Available Transient Receptor Potential (TRP proteins are a large family of ion channels, grouped intoseven sub-families. Although great advances have been made regarding the activation andmodulation of TRP channel activity, detailed molecular mechanisms governing TRPchannel gating are still needed. Sensitive to electric, chemical, mechanical, and thermalcues, TRP channels are tightly associated with the detection and integration of sensoryinput, emerging as a model to study the polymodal activation of ion channel proteins.Among TRP channels, the temperature-activated kind constitute a subgroup by itself,formed by Vanilloid receptors 1-4, Melastatin receptors 2, 4, 5 and 8, TRPC5, and TRPA1.Some of the so-called thermoTRP channels participate in the detection of noxious stimulimaking them an interesting pharmacological target for the treatment of pain. However, thepoor specificity of the compounds available in the market represents an important obstacleto overcome. Understanding the molecular mechanics underlying ligand-dependentmodulation of TRP channels may help with the rational design of novel syntheticanalgesics. The present review focuses on the structural basis of ligand-dependentactivation of TRPV1 and TRPM8 channels. Special attention is drawn to the dissection ofligand-binding sites within TRPV1, PIP 2 -dependent modulation of TRP channels, and thestructure of natural and synthetic ligands.

  19. UV-induced tandem double mutations in the trpA gene of E. coli

    International Nuclear Information System (INIS)

    Piechocki, R.; Langhammer, R.

    1980-01-01

    The ultraviolet light induction of tandem double mutations in a reverse mutation system was shown using trpA mutants which are characterized by the codon sequences GAA and AAG in codon position 211. Among 597 Trp + independent revertants of the trpA (AAG211) strain 3 full revertants were detected arising from UV-induced tandem double base exchanges. In the codon unit 211 full revertants due to single base exchanges are at least 20 times as frequent as full revertants due to tandem double base exchanges. (author)

  20. The Thrift Industry and the Community Reinvestment Act: Assessing the Cost of Social Responsibility

    OpenAIRE

    Donald F. Vitaliano; Gregory Stella

    2003-01-01

    A stochastic frontier cost function indicates that the annual cost of complying with the anti-redlining Community Reinvestment Act (CRA) is $171,000 per thrift institution, roughly 2.3 percent of variable costs. But compliance cost is significantly less than the estimated 21 percent cost inefficiency. Based on published estimates of the incremental number of mortgage loans induced by CRA, the marginal cost is $38,000 per loan. The regulations whose compliance cost is estimated apply to about ...

  1. Influence of focus of attention, reinvestment and fall history on elderly gait stability.

    Science.gov (United States)

    de Melker Worms, Jonathan L A; Stins, John F; van Wegen, Erwin E H; Loram, Ian D; Beek, Peter J

    2017-01-01

    Falls represent a substantial risk in the elderly. Previous studies have found that a focus on the outcome or effect of the movement (external focus of attention) leads to improved balance performance, whereas a focus on the movement execution itself (internal focus of attention) impairs balance performance in elderly. A shift toward more conscious, explicit forms of motor control occurs when existing declarative knowledge is recruited in motor control, a phenomenon called reinvestment. We investigated the effects of attentional focus and reinvestment on gait stability in elderly fallers and nonfallers. Full body kinematics was collected from twenty-eight healthy older adults walking on a treadmill, while focus of attention was manipulated through instruction. Participants also filled out the Movement Specific Reinvestment Scale (MSRS) and the Falls Efficacy Scale International (FES-I), and provided details about their fall history. Coefficients of Variation (CV) of spatiotemporal gait parameters and Local Divergence Exponents (LDE) were calculated as measures of gait variability and gait stability, respectively. Larger stance time CV and LDE (decreased gait stability) were found for fallers compared to nonfallers. No significant effect of attentional focus was found for the gait parameters, and no significant relation between MSRS score (reinvestment) and fall history was found. We conclude that external attention to the walking surface does not lead to improved gait stability in elderly. Potential benefits of an external focus of attention might not apply to gait, because walking movements are not geared toward achieving a distinct environmental effect. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  2. Breathing new life into your production irradiator the case for reinvesting in your facility

    International Nuclear Information System (INIS)

    Aube, Robert; Wynnyk, Mike

    2002-01-01

    This paper focuses on one of the important technology issues facing the gamma processing industry today: that of strategically planning for extending the useful life of a production irradiator. Production irradiator owners are typically faced with the difficult question of whether or not to significantly reinvest in their facilities after 15-20 years of service. At this point in time the irradiator has likely provided many years of safe, reliable service and has paid for itself many times over. As the equipment ages, it may become less reliable, due to wear and maintenance practices, and more costly to operate. The cost of refurbishing the equipment may be significant and the downtime required to complete the refurbishment is also likely to be a challenge. This makes it essential to present a clear and rational justification for reinvesting in the facility. There has been a growing trend in recent years for irradiator owners to refurbish or upgrade their facilities. This trend is driven by the need to keep the facilities operating efficiently and safely as well as by the desire to take advantage of advancements that have occurred in the technology over the years. These advancements can enhance equipment efficiency, improve operational effectiveness and maintain or exceed quality assurance requirements. This paper illustrates the value of reinvesting in irradiator facilities, and highlights the significant benefits derived

  3. Safety evaluation of Tokai reprocessing plant (TRP). Report of safety evaluation of Tokai reprocessing plant

    International Nuclear Information System (INIS)

    Yamauchi, Takamichi; Maki, Akira; Nojiri, Ichiro

    1999-02-01

    The fire and explosion incident of the bituminization facility happened in March 1997 although JNC had taken enough care of the safety of TRP. JNC reflected on it and decided to evaluate the safety of TRP voluntarily. This evaluation has included five activities, that is, (1) confirmation of the structure and organization of TRP, (2) research of the data for operation, radiation and maintenance of TRP, (3) research of reflection of the accidents and troubles which have happened at the past, (4) evaluation on the prevention system, (5) evaluation on the mitigation system. We publish this report to contribute to inheritance of accumulated knowledge and techniques from generation to generation, and remind us of lesson from the fire and explosion incident of the bituminization. (author)

  4. Immunolocalization and distribution of functional temperature-sensitive TRP channels in salivary glands.

    Science.gov (United States)

    Sobhan, Ubaidus; Sato, Masaki; Shinomiya, Takashi; Okubo, Migiwa; Tsumura, Maki; Muramatsu, Takashi; Kawaguchi, Mitsuru; Tazaki, Masakazu; Shibukawa, Yoshiyuki

    2013-11-01

    Transient receptor potential (TRP) cation channels are unique cellular sensors involved in multiple cellular functions. Their role in salivary secretion remains to be elucidated. The expression and localization of temperature-sensitive TRP channels in salivary (submandibular, sublingual and parotid) glands were analyzed by immunohistochemistry and quantitative real-time reverse transcription plus the polymerase chain reaction (RT-PCR). The effects of various TRP channel agonists on carbachol (CCh)-induced salivary secretion in the submandibular gland and on the intracellular Ca(2+) concentration ([Ca(2+)]i) in a submandibular epithelial cell line were also investigated. Immunohistochemistry revealed the expression of TRP-melastatin subfamily member 8 (TRPM8) and TRP-ankyrin subfamily member 1 (TRPA1) in myoepithelial, acinar and ductal cells in the sublingual, submandibular and parotid glands. In addition, TRP-vanilloid subfamily member 1 (TRPV1), TRPV3 and TRPV4 were also expressed in myoepithelial, acinar and ductal cells in all three types of gland. Quantitative real-time RT-PCR results demonstrated the mRNA expression of TRPV1, TRPV3, TRPV4, TRPM8 and TRPA1 in acinar and ductal cells in these salivary glands. Perfusion of the entire submandibular gland with the TRPV1 agonist capsaicin (1 μM) via the submandibular artery significantly increased CCh-induced salivation, whereas perfusion with TRPM8 and TRPA1 agonists (0.5 μM WS12 and 100 μM allyl isothiocyanate) decreased it. Application of agonists for each of the thermosensitive TRP channels increased [Ca(2+)]i in a submandibular epithelial cell line. These results indicate that temperature-sensitive TRP channels are localized and distributed in acinar, ductal and myoepithelial cells in salivary glands and that they play a functional role in the regulation and/or modulation of salivary secretion.

  5. Membrane-tethered peptides patterned after the TRP domain (TRPducins) selectively inhibit TRPV1 channel activity.

    Science.gov (United States)

    Valente, Pierluigi; Fernández-Carvajal, Asia; Camprubí-Robles, María; Gomis, Ana; Quirce, Susana; Viana, Félix; Fernández-Ballester, Gregorio; González-Ros, José M; Belmonte, Carlos; Planells-Cases, Rosa; Ferrer-Montiel, Antonio

    2011-05-01

    The transient receptor potential vanilloid 1 (TRPV1) channel is a thermosensory receptor implicated in diverse physiological and pathological processes. The TRP domain, a highly conserved region in the C terminus adjacent to the internal channel gate, is critical for subunit tetramerization and channel gating. Here, we show that cell-penetrating, membrane-anchored peptides patterned after this protein domain are moderate and selective TRPV1 antagonists both in vitro and in vivo, blocking receptor activity in intact rat primary sensory neurons and their peripheral axons with mean decline time of 30 min. The most potent lipopeptide, TRP-p5, blocked all modes of TRPV1 gating with micromolar efficacy (IC(50)100 μM). TRP-p5 did not affect the capsaicin sensitivity of the vanilloid receptor. Our data suggest that TRP-p5 interferes with protein-protein interactions at the level of the TRP domain that are essential for the "conformational" change that leads to gate opening. Therefore, these palmitoylated peptides, which we termed TRPducins, are noncompetitive, voltage-independent, sequence-specific TRPV1 blockers. Our findings indicate that TRPducin-like peptides may embody a novel molecular strategy that can be exploited to generate a selective pharmacological arsenal for the TRP superfamily of ion channels.

  6. Antioxidant and antiglycation activities of the synthesised dipeptide, Asn-Trp, derived from computer-aided simulation of yam dioscorin hydrolysis and its analogue, Gln-Trp.

    Science.gov (United States)

    Han, Chuan-Hsiao; Lin, Yin-Shiou; Lin, Shyr-Yi; Hou, Wen-Chi

    2014-03-15

    Previous studies have shown that the Trp residue contributes to a high oxygen radical absorbance capacity (ORAC). Therefore, in this study, a Trp-containing dipeptide derived from a computer-aided simulation of pepsin hydrolysis of the yam tuber, dioscorin-namely, Asn-Trp (NW), and its analogue, Gln-Trp (QW)-were synthesised to compare their antioxidant and antiglycation activities with carnosine, homocarnosine, or glutathione (GSH). The antioxidant assays included hydroxyl radical-scavenging activity, anti-AAPH-induced hemolysis, and ORAC activity. NW had a significantly higher antioxidant activity than had QW and performed much better than carnosine, homocarnosine, or GSH. Using bovine serum albumin (BSA)/galactose or BSA/glucose as experimental models, NW had better antiglycation effects than had QW, as detected by an anti-N(ε)-(carboxymethyl)lysine (anti-CML) antibody. Moreover, NW and QW (50-200 μM) showed protection against methylglyoxal-induced cell deaths in human umbilical vein endothelial cells. These results suggest that NW, derived from computer-aided simulation of dioscorin hydrolysis, exhibits antioxidant and antiglycation activities, which thus shows the benefits of the yam tuber as an antioxidant-rich food. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. BAX and tumor suppressor TRP53 are important in regulating mutagenesis in spermatogenic cells in mice.

    Science.gov (United States)

    Xu, Guogang; Vogel, Kristine S; McMahan, C Alex; Herbert, Damon C; Walter, Christi A

    2010-12-01

    During the first wave of spermatogenesis, and in response to ionizing radiation, elevated mutant frequencies are reduced to a low level by unidentified mechanisms. Apoptosis is occurring in the same time frame that the mutant frequency declines. We examined the role of apoptosis in regulating mutant frequency during spermatogenesis. Apoptosis and mutant frequencies were determined in spermatogenic cells obtained from Bax-null or Trp53-null mice. The results showed that spermatogenic lineage apoptosis was markedly decreased in Bax-null mice and was accompanied by a significantly increased spontaneous mutant frequency in seminiferous tubule cells compared to that of wild-type mice. Apoptosis profiles in the seminiferous tubules for Trp53-null were similar to control mice. Spontaneous mutant frequencies in pachytene spermatocytes and in round spermatids from Trp53-null mice were not significantly different from those of wild-type mice. However, epididymal spermatozoa from Trp53-null mice displayed a greater spontaneous mutant frequency compared to that from wild-type mice. A greater proportion of spontaneous transversions and a greater proportion of insertions/deletions 15 days after ionizing radiation were observed in Trp53-null mice compared to wild-type mice. Base excision repair activity in mixed germ cell nuclear extracts prepared from Trp53-null mice was significantly lower than that for wild-type controls. These data indicate that BAX-mediated apoptosis plays a significant role in regulating spontaneous mutagenesis in seminiferous tubule cells obtained from neonatal mice, whereas tumor suppressor TRP53 plays a significant role in regulating spontaneous mutagenesis between postmeiotic round spermatid and epididymal spermatozoon stages of spermiogenesis.

  8. American Recovery and Reinvestment Act (ARRA) FEMP Technical Assistance

    Energy Technology Data Exchange (ETDEWEB)

    Robert P. Breckenridge; Thomas R. Wood

    2010-08-01

    The purpose of this document is to evaluate the opportunity for Letterkenny Army Depot (LEAD or the Depot) to utilize biogenic methane, which may be available in shale formations under the Depot, to provide a supplemental source of natural gas that could allow the Depot to increase energy independence. Both the Director and Deputy of Public Works at the Depot are supportive in general of a methane production project, but wanted to better understand the challenges prior to embarking on such a project. This report will cover many of these issues. A similar project has been successfully developed by the U. S. Army at Ft. Knox, KY, which will be explained and referred to throughout this report as a backdrop to discussing the challenges and opportunities at LEAD, because the geologic formations and possibilities at both sites are similar. Prior to discussing the opportunity at LEAD, it is important to briefly discuss the successful methane recovery operation at Ft. Knox, because it is applicable to the projected approach for the LEAD methane system. The Ft. Knox project is an excellent example of how the U. S. Army can use an onsite renewable resource to provide a secure energy source that is not dependent on regional energy networks and foreign oil. At Ft. Knox, the U. S. Army contracted (through a utility co-op) with an energy production company to drill wells, establish a distribution infrastructure, and provide the equipment needed to prepare and compress the produced methane gas for use by base operations. The energy production company agreed to conduct the exploratory investigation at Ft. Knox with no cost to the government, as long as they could be granted a long-term contract if a reliable energy resource was established. The Depot is located, in part, over an Ordovician Age shale formation that may have the potential for producing biogenic methane, similar to the Devonian Age shale found beneath Ft. Knox. However, the Ordovician Age Shale beneath the

  9. Structure-activity relationship of linear peptide Bu-His6-DPhe7-Arg8-Trp9-Gly10-NH2 at the human melanocortin-1 and -4 receptors: DPhe7 and Trp9 substitution.

    Science.gov (United States)

    Danho, Waleed; Swistok, Joseph; Cheung, Adrian Wai-Hing; Kurylko, Grazyna; Franco, Lucia; Chu, Xin-Jie; Chen, Li; Yagaloff, Keith

    2003-02-24

    A series of pentapeptides, based on hMC4R pentapeptide agonist (Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2)), was prepared in which either DPhe(7) or Trp(9) residue was systematically substituted. A number of interesting DPhe surrogates (D-Thi, D-3-CF(3)Phe, D-2-Nal and D-3,4-diClPhe) as well as Trp surrogates (2-Nal and Bta) were identified in this study.

  10. Pulse radiolysis studies of intramolecular electron transfer in model peptides and proteins. 7. Trp -> TyrO radical transformation in hen egg-white lysozyme. Effects of pH, temperature, Trp62 oxidation and inhibitor binding

    DEFF Research Database (Denmark)

    Bobrowski, K.; Holcman, J.; Poznanski, J.

    1997-01-01

    Intramolecular long-range electron transfer (LRET) in hen egg-white lysozyme (HEWL) accompanying Trp --> TyrO radical transformation was investigated in aqueous solution by pulse radiolysis as a function of pH (5.2-7.4) and temperature (283-328K). The reaction was induced by highly selective...... below its denaturation temperature. Selective oxidation by ozone of the Trp62 indole side-chain in HEWL to N'-formylkynurenine (NFKyn62-HEWL) caused a large drop in the initial yield of Trp(.) radicals, G(Trp(.))(i). This was accompanied by a relatively small decrease in k(5) but selective oxidation...

  11. Loss of Cdh1 and Trp53 in the uterus induces chronic inflammation with modification of tumor microenvironment

    OpenAIRE

    Stodden, Genna R.; Lindberg, Mallory E.; King, Mandy L.; Paquet, Maril?ne; MacLean, James A.; Mann, Jordan L.; DeMayo, Francesco J.; Lydon, John P.; Hayashi, Kanako

    2014-01-01

    Type II endometrial carcinomas are estrogen independent, poorly differentiated tumors that behave in an aggressive manner. Since TP53 mutation and CDH1 inactivation occur in 80% of human endometrial type II carcinomas, we hypothesized that mouse uteri lacking both Trp53 and Cdh1 would exhibit a phenotype indicative of neoplastic transformation. Mice with conditional ablation of Cdh1 and Trp53 (Cdh1d/dTrp53d/d ) clearly demonstrate architectural features characteristic of type II endometrial c...

  12. Ehrlichia chaffeensis TRP120 Activates Canonical Notch Signaling To Downregulate TLR2/4 Expression and Promote Intracellular Survival

    OpenAIRE

    Lina, Taslima T.; Dunphy, Paige S.; Luo, Tian; McBride, Jere W.

    2016-01-01

    ABSTRACT Ehrlichia chaffeensis preferentially targets mononuclear phagocytes and survives through a strategy of subverting innate immune defenses, but the mechanisms are unknown. We have shown E.?chaffeensis type 1 secreted tandem repeat protein (TRP) effectors are involved in diverse molecular pathogen-host interactions, such as the TRP120 interaction with the Notch receptor-cleaving metalloprotease ADAM17. In the present study, we demonstrate E.?chaffeensis, via the TRP120 effector, activat...

  13. Results From the Audit of DOD’s American Recovery and Reinvestment Act of 2009 Initial Data Quality Review Implementation

    Science.gov (United States)

    2009-11-03

    Results From the Audit of DoD’s American Recovery and Reinvestment Act of 2009 Initial Data Quality Review Implementation Memorandum No. D-2010-RAM...number. 1. REPORT DATE 03 NOV 2009 2. REPORT TYPE 3. DATES COVERED 00-00-2009 to 00-00-2009 4. TITLE AND SUBTITLE Results From the Audit of...SUBJECT: Results From the Audit of DOD’ s American Recovery and Reinvestment Act of2009 Initial Data Quality Review Implementation (Report No. D

  14. Thermo-sensitive TRP channels in peripheral nerve injury: a review of their role in cold intolerance.

    Science.gov (United States)

    Kambiz, S; Duraku, L S; Holstege, J C; Hovius, S E R; Ruigrok, T J H; Walbeehm, E T

    2014-05-01

    One of the sensory complications of traumatic peripheral nerve injury is thermal intolerance, which manifests in humans mainly as cold intolerance. It has a major effect on the quality of life, and adequate therapy is not yet available. In order to better understand the pathophysiological background of thermal intolerance, we focus first on the various transient receptor potential (TRP) channels that are involved in temperature sensation, including their presence in peripheral nerves and in keratinocytes. Second, the role of thermo-sensitive TRP channels in cold and heat intolerance is described showing three different mechanisms that contribute to thermal intolerance in the skin: (a) an increased expression of TRP channels on nerve fibres and on keratinocytes, (b) a lower activation threshold of TRP channels and (c) the sprouting of non-injured nerve fibres. Finally, the data that are available on the effects of TRP channel agonists and antagonists and their clinical use are discussed. In conclusion, TRP channels play a major role in temperature sensation and in cold and heat intolerance. Unfortunately, the available pharmaceutical agents that successfully target TRP channels and counteract thermal intolerance are still very limited. Yet, our focus should remain on TRP channels since it is difficult to imagine a reliable treatment for thermal intolerance that will not involve TRP channels. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  15. An Allelic Series of Trp63 Mutations Defines TAp63 as a Modifier of EEC Syndrome

    Science.gov (United States)

    Lindahl, Emma Vernersson; Garcia, Elvin L.; Mills, Alea A.

    2014-01-01

    Human Ectrodactyly, Ectodermal dysplasia, Clefting (EEC) syndrome is an autosomal dominant developmental disorder defined by limb deformities, skin defects, and craniofacial clefting. Although associated with heterozygous missense mutations in TP63, the genetic basis underlying the variable expressivity and incomplete penetrance of EEC is unknown. Here we show that mice heterozygous for an allele encoding the Trp63 p.Arg318His mutation, which corresponds to the human TP63 p.Arg279His mutation found in patients with EEC, have features of human EEC. Using an allelic series, we discovered that whereas clefting and skin defects are caused by loss of Trp63 function, limb anomalies are due to gain- and/or dominant-negative effects of Trp63. Furthermore, we identify TAp63 as a strong modifier of EEC-associated phenotypes with regard to both penetrance and expressivity. PMID:23775923

  16. A thermodynamic framework for understanding temperature sensing by transient receptor potential (TRP) channels.

    Science.gov (United States)

    Clapham, David E; Miller, Christopher

    2011-12-06

    The exceptionally high temperature sensitivity of certain transient receptor potential (TRP) family ion channels is the molecular basis of hot and cold sensation in sensory neurons. The laws of thermodynamics dictate that opening of these specialized TRP channels must involve an unusually large conformational standard-state enthalpy, ΔH(o): positive ΔH(o) for heat-activated and negative ΔH(o) for cold-activated TRPs. However, the molecular source of such high-enthalpy changes has eluded neurobiologists and biophysicists. Here we offer a general, unifying mechanism for both hot and cold activation that recalls long-appreciated principles of protein folding. We suggest that TRP channel gating is accompanied by large changes in molar heat capacity, ΔC(P). This postulate, along with the laws of thermodynamics and independent of mechanistic detail, leads to the conclusion that hot- and cold-sensing TRPs operate by identical conformational changes.

  17. Opportunities in the American Recovery and Reinvestment Act for Supports and Services for Youth Transitioning from Foster Care

    Science.gov (United States)

    Flynn-Khan, Margaret; Langford, Barbara Hanson

    2009-01-01

    To address the economic crisis facing the country, the President signed the American Recovery and Reinvestment Act (ARRA) into law on February 17, 2009. This sweeping legislation provides $789 billion to jumpstart the economy and boost employment. This act includes $463 billion in new spending and $326 billion in tax relief directed at those…

  18. 75 FR 37456 - Green Retrofit Program of Title XII of the American Recovery and Reinvestment Act of 2009

    Science.gov (United States)

    2010-06-29

    ... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5376-N-55] Green Retrofit Program of... Affordable Housing Preservation must collect certain data to administer the Green Retrofit Program (GRP... Title of Proposal: Green Retrofit Program of Title XII of the American Recovery and Reinvestment Act of...

  19. 77 FR 11163 - Notice of Buy American Waiver Under the American Recovery and Reinvestment Act of 2009

    Science.gov (United States)

    2012-02-24

    ...) companies world-wide were identified that manufacture ABS approved anchors of superior holding anchors. Of... NATIONAL SCIENCE FOUNDATION Notice of Buy American Waiver Under the American Recovery and Reinvestment Act of 2009 AGENCY: National Science Foundation (NSF). ACTION: Notice. SUMMARY: NSF is hereby...

  20. 76 FR 35920 - Notice of Buy American Waiver Under the American Recovery and Reinvestment Act of 2009

    Science.gov (United States)

    2011-06-20

    ... antifouling system was done by UAF in 2009. Only two sources were identified world-wide and none were... NATIONAL SCIENCE FOUNDATION Notice of Buy American Waiver Under the American Recovery and Reinvestment Act of 2009 AGENCY: National Science Foundation (NSF). ACTION: Notice. SUMMARY: NSF is hereby...

  1. Interaction between the Gly460Trp alpha-adducin gene variant and diuretics on the risk of myocardial infarction

    NARCIS (Netherlands)

    van Wieren-de Wijer, Diane B M A; Maitland-van der Zee, Anke-Hilse; de Boer, Anthonius; Kroon, Abraham A; de Leeuw, Peter W; Schiffers, Paul; Janssen, Rob G J H; Psaty, Bruce M; van Duijn, Cornelia M; Stricker, Bruno H Ch; Klungel, Olaf H

    INTRODUCTION: The Gly460Trp variant of the alpha-adducin gene has been associated with the salt-sensitive and diuretic responsive form of hypertension. OBJECTIVE: The aim of the study was to determine whether the alpha-adducin 460Trp variant allele modifies the risk-lowering effect of diuretics on

  2. Byzantské "drama" Trpící Kristus

    Czech Academy of Sciences Publication Activity Database

    Fialová, Radka

    2012-01-01

    Roč. 23, č. 1 (2012), s. 30-45 ISSN 0862-5409 R&D Projects: GA ČR(CZ) GBP401/12/G168 Institutional support: RVO:67985955 Keywords : Byzantine drama * Passion of Christ * Ancient Greek tragedy Subject RIV: AJ - Letters, Mass-media, Audiovision

  3. Structural domains required for channel function of the mouse transient receptor potential protein homologue TRP1beta.

    Science.gov (United States)

    Engelke, Michael; Friedrich, Olaf; Budde, Petra; Schäfer, Christina; Niemann, Ursula; Zitt, Christof; Jüngling, Eberhard; Rocks, Oliver; Lückhoff, Andreas; Frey, Jürgen

    2002-07-17

    Transient receptor potential proteins (TRP) are supposed to participate in the formation of store-operated Ca(2+) influx channels by co-assembly. However, little is known which domains facilitate the interaction of subunits. Contribution of the N-terminal coiled-coil domain and ankyrin-like repeats and the putative pore region of the mouse TRP1beta (mTRP1beta) variant to the formation of functional cation channels were analyzed following overexpression in HEK293 (human embryonic kidney) cells. MTRP1beta expressing cells exhibited enhanced Ca(2+) influx and enhanced whole-cell membrane currents compared to mTRP1beta deletion mutants. Using a yeast two-hybrid assay only the coiled-coil domain facilitated homodimerization of the N-terminus. These results suggest that the N-terminus of mTRP1beta is required for structural organization thus forming functional channels.

  4. Prostaglandin H synthase-mediated bioactivation of the amino acid pyrolysate product Trp P-2

    Energy Technology Data Exchange (ETDEWEB)

    Petry, T.W.; Krauss, R.S.; Eling, T.E.

    1986-08-01

    We report evidence that the mutagen and carcinogen 3-amino-1-methyl-5H pyrido(4,3b)indole (Trp P-2) is a substrate for co-oxidation by prostaglandin H synthase (PHS) in ram seminal vesicle (RSV) microsomes. Trp P-2 serves as a reducing cofactor for the hydroperoxidase activity of PHS as shown by the concentration-dependent inhibition of the hydroperoxidase catalyzed incorporation of molecular oxygen into phenylbutazone. Spectral data suggest that this metabolism results in disruption of the double bond conjugation within the nucleus of the molecule. A single metabolite peak which was dependent upon arachidonic acid and substrate concentration was separated from the parent compound by h.p.l.c. following incubation with RSV microsomes. Co-oxidation of Trp P-2 produced reactive intermediates which bound covalently to microsomal protein (9 nmol/mg) and to calf thymus DNA (475 pmol/mg). Binding was inhibited by indomethacin, and supported by substitution of hydrogen peroxide for arachidonic acid. These data suggest a possible role for PHS in the in situ activation of Trp P-2 to its ultimate carcinogenic form in tissues which contain PHS.

  5. A survey on the biochemical parameters in serum of the Azarbaijan buffaloes with TRP

    Directory of Open Access Journals (Sweden)

    Gh. Mousavi

    2010-02-01

    Full Text Available TRP disease is one of the prevalent disease in cows and buffaloes that most common in dairy cows feed by prepared foods but cases occur infrequently in buffaloes, beef cattle, sheep and goats. In this research 15 Azerbaijan buffaloes with TRP were studied. Firstly affected buffaloes were diagnosed based on clinical signs. The blood samples were obtained from the related animals and after separation blood serum by centrifuging, the biochemical tests, such as sodium, potassium, Glucose, phosphorus, albumin and calcium levels in serum were measured. The mean levels of sodium, potassium, Glucose, phosphorus, albumin and calcium in buffaloes with TRP were 112 mEq/Lit, 3.11 mEq/Lit, 42.29 mg/dl, 3.84 mg/dl, 544 mg/dl, 8.60 mg/dl. In this study the mean levels of sodium, potassium, phosphorus in buffaloes with TRP was less than the normal buffaloes and the mean levels of calcium, Glucose as such as the normal animals and the mean levels of albumin was higher than the normal buffaloes.

  6. Rate constant and reaction coordinate of Trp-cage folding in explicit water

    NARCIS (Netherlands)

    Juraszek, J.; Bolhuis, P.G.

    2008-01-01

    We report rate constant calculations and a reaction coordinate analysis of the rate-limiting folding and unfolding process of the Trp-cage mini-protein in explicit solvent using transition interface sampling. Previous transition path sampling simulations revealed that in this (un)folding process the

  7. Alpha-adducin Gly460Trp polymorphism and renal hemodynamics in essential hypertension

    NARCIS (Netherlands)

    Beeks, Esther; van der Klauw, Melanie M; Kroon, Abraham A; Spiering, Wilko; Fuss-Lejeune, Monique J M J; de Leeuw, Peter W

    2004-01-01

    Previous studies have shown an association between the alpha-adducin Gly460Trp polymorphism and salt-sensitive hypertension. Not much is known about the effects of the variants of this polymorphism on renal hemodynamics and function. Therefore, we performed the present study to investigate the

  8. Trp53 activity is repressed in radio-adapted cultured murine limb bud cells

    International Nuclear Information System (INIS)

    Vares, Guillaume; Wang, Bing; Tanaka, Kaoru; Shang, Yi; Fujita, Kazuko; Hayata, Isamu; Nenoi, Mitsuru

    2011-01-01

    Understanding the effects of ionizing radiation (IR) at low dose in fetal models is of great importance, because the fetus is considered to be at the most radiosensitive stage of the development and prenatal radiation might influence subsequent development. We previously demonstrated the existence of an adaptive response (AR) in murine fetuses after pre-exposure to low doses of X-rays. Trp53-dependent apoptosis was suggested to be responsible for the teratogenic effects of IR; decreased apoptosis was observed in adapted animals. In this study, in order to investigate the role of Trp53 in AR, we developed a new model of irradiated micromass culture of fetal limb bud cells, which replicated proliferation, differentiation and response to IR in murine embryos. Murine fetuses were exposed to whole-body priming irradiation of 0.3 Gy or 0.5 Gy at embryonic day 11 (E11). Limb bud cells (collected from digital ray areas exhibiting radiation-induced apoptosis) were cultured and exposed to a challenging dose of 4 Gy at E12 equivalent. The levels of Trp53 protein and its phosphorylated form at Ser18 were investigated. Our results suggested that the induction of AR in mouse embryos was correlated with a repression of Trp53 activity. (author)

  9. Sampling the equilibrium kinetic network of Trp-cage in explicit solvent

    NARCIS (Netherlands)

    Du, W.; Bolhuis, P.G.

    2014-01-01

    We employed the single replica multiple state transition interface sampling (MSTIS) approach to sample the kinetic (un) folding network of Trp-cage mini-protein in explicit water. Cluster analysis yielded 14 important metastable states in the network. The MSTIS simulation thus resulted in a full 14

  10. A direct comparison of protein structure in the gas and solution phase: the Trp-cage

    DEFF Research Database (Denmark)

    Patriksson, Alexandra; Adams, Christopher M; Kjeldsen, Frank

    2007-01-01

    Molecular dynamics simulations of zwitterions of the Trp-cage protein in the gas phase show that the most stable ion in vacuo has preserved the charge locations acquired in solution. A direct comparison of the gas and solution-phase structures reveals that, despite the similarity in charge location...

  11. Spectroscopic evidence for an engineered, catalytically active Trp radical that creates the unique reactivity of lignin peroxidase.

    Science.gov (United States)

    Smith, Andrew T; Doyle, Wendy A; Dorlet, Pierre; Ivancich, Anabella

    2009-09-22

    The surface oxidation site (Trp-171) in lignin peroxidase (LiP) required for the reaction with veratryl alcohol a high-redox-potential (1.4 V) substrate, was engineered into Coprinus cinereus peroxidase (CiP) by introducing a Trp residue into a heme peroxidase that has similar protein fold but lacks this activity. To create the catalytic activity toward veratryl alcohol in CiP, it was necessary to reproduce the Trp site and its negatively charged microenvironment by means of a triple mutation. The resulting D179W+R258E+R272D variant was characterized by multifrequency EPR spectroscopy. The spectra unequivocally showed that a new Trp radical [g values of g(x) = 2.0035(5), g(y) = 2.0027(5), and g(z) = 2.0022(1)] was formed after the [Fe(IV)=O Por(*+)] intermediate, as a result of intramolecular electron transfer between Trp-179 and the porphyrin. Also, the EPR characterization crucially showed that [Fe(IV)=O Trp-179(*)] was the reactive intermediate with veratryl alcohol. Accordingly, our work shows that it is necessary to take into account the physicochemical properties of the radical, fine-tuned by the microenvironment, as well as those of the preceding [Fe(IV)=O Por(*+)] intermediate to engineer a catalytically competent Trp site for a given substrate. Manipulation of the microenvironment of the Trp-171 site in LiP allowed the detection by EPR spectroscopy of the Trp-171(*), for which direct evidence has been missing so far. Our work also highlights the role of Trp residues as tunable redox-active cofactors for enzyme catalysis in the context of peroxidases with a unique reactivity toward recalcitrant substrates that require oxidation potentials not realized at the heme site.

  12. Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system

    Science.gov (United States)

    Holzer, Peter

    2011-01-01

    Approximately 20 of the 30 mammalian transient receptor potential (TRP) channel subunits are expressed by specific neurons and cells within the alimentary canal. They subserve important roles in taste, chemesthesis, mechanosensation, pain and hyperalgesia and contribute to the regulation of gastrointestinal motility, absorptive and secretory processes, blood flow, and mucosal homeostasis. In a cellular perspective, TRP channels operate either as primary detectors of chemical and physical stimuli, as secondary transducers of ionotropic or metabotropic receptors, or as ion transport channels. The polymodal sensory function of TRPA1, TRPM5, TRPM8, TRPP2, TRPV1, TRPV3 and TRPV4 enables the digestive system to survey its physical and chemical environment, which is relevant to all processes of digestion. TRPV5 and TRPV6 as well as TRPM6 and TRPM7 contribute to the absorption of Ca2+ and Mg2+, respectively. TRPM7 participates in intestinal pacemaker activity, and TRPC4 transduces muscarinic acetylcholine receptor activation to smooth muscle contraction. Changes in TRP channel expression or function are associated with a variety of diseases/disorders of the digestive system, notably gastro-esophageal reflux disease, inflammatory bowel disease, pain and hyperalgesia in heartburn, functional dyspepsia and irritable bowel syndrome, cholera, hypomagnesemia with secondary hypocalcemia, infantile hypertrophic pyloric stenosis, esophageal, gastrointestinal and pancreatic cancer, and polycystic liver disease. These implications identify TRP channels as promising drug targets for the management of a number of gastrointestinal pathologies. As a result, major efforts are put into the development of selective TRP channel agonists and antagonists and the assessment of their therapeutic potential. PMID:21420431

  13. Structure-activity relationship of Trp-containing analogs of the antimicrobial peptide gomesin.

    Science.gov (United States)

    Domingues, Tatiana M; Buri, Marcus V; Daffre, Sirlei; Campana, Patricia T; Riske, Karin A; Miranda, Antonio

    2014-06-01

    Gomesin (Gm) has a broad antimicrobial activity making it of great interest for development of drugs. In this study, we analyzed three Gm analogs, [Trp(1) ]-Gm, [Trp(7) ]-Gm, and [Trp(9) ]-Gm, in an attempt to gain insight into the contributions of different regions of the peptide sequence to its activity. The incorporation of the tryptophan residue in different positions has no effect on the antimicrobial and hemolytic activities of the Gm analogs in relation to Gm. Spectroscopic studies (circular dichroism, fluorescence and absorbance) of Gm and its analogs were performed in the presence of SDS, below and above its critical micelle concentration (CMC) (~8 mM), in order to monitor structural changes induced by the interaction with this anionic surfactant (0-15 mM). Interestingly, we found that the analogs interact more strongly with SDS at low concentrations (0.3-6.0 mM) than close to or above its CMC. This suggests that SDS monomers are able to cover the whole peptide, forming large detergent-peptide aggregates. On the other hand, the peptides interact differently with SDS micelles, inserting partially into the micelle core. Among the peptides, Trp in position 1 becomes more motionally-restricted in the presence of SDS, probably because this residue is located at the N-terminal region, which presents higher conformational freedom to interact stronger with SDS molecules. Trp residues in positions 7 and 9, close to and in the region of the turn of the molecule, respectively, induced a more constrained structure and the compounds cannot insert deeper into the micelle core or be completely buried by SDS monomers. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

  14. Downsizing Prisons in an Age of Austerity? Justice Reinvestment and Women’s Imprisonment

    Directory of Open Access Journals (Sweden)

    Julie Stubbs

    2016-03-01

    Full Text Available Justice Reinvestment is being actively promoted as one means of reducing high levels of incarceration through diverting expenditures from prisons to fund services intended to provide support and supervision for offenders within the community and to prevent crime. At a time of financial stringency, the huge expenditure necessitated by high incarceration rates is being re-examined. There is growing recognition that high levels of incarceration are ineffective in reducing recidivism and may be criminogenic and damaging in other ways for individuals and communities. Based on claims that Justice Reinvestment schemes in the US have produced promising results, some activists and politicians in Australia have urged the adoption of Justice Reinvestment. This advocacy has emphasised the need to find mechanisms to reduce the very high levels of incarceration of Indigenous people. Women’s imprisonment rates have increased substantially in recent years and to a greater extent than rates for men. This pattern has been observed in several jurisdictions and is even more pronounced for Indigenous women. This paper critically examines features of Justice Reinvestment, such as its endorsement of ‘evidence based policy’ and risk assessment tools, to question whether these features are likely to promote the interests of women. Se está promoviendo activamente la reinversión en justicia como un medio para reducir las altas tasas de encarcelamiento, dedicando gastos destinados a prisiones para financiar servicios dentro de la comunidad que presten apoyo y supervisión a los delincuentes y que prevengan el delito. En un momento de restricciones financieras, se está revisando el enorme gasto que generan las altas tasas de encarcelamiento. Existe un creciente reconocimiento de que una alta tasa de encarcelamiento no es eficaz para reducir la reincidencia y, de diversas maneras, puede aumentar la criminalidad y ser perjudicial para individuos y comunidades. Bas

  15. A Direct in Vivo Comparison of the Melanocortin Monovalent Agonist Ac-His-DPhe-Arg-Trp-NH2 versus the Bivalent Agonist Ac-His-DPhe-Arg-Trp-PEDG20-His-DPhe-Arg-Trp-NH2: A Bivalent Advantage.

    Science.gov (United States)

    Lensing, Cody J; Adank, Danielle N; Wilber, Stacey L; Freeman, Katie T; Schnell, Sathya M; Speth, Robert C; Zarth, Adam T; Haskell-Luevano, Carrie

    2017-06-21

    Bivalent ligands targeting putative melanocortin receptor dimers have been developed and characterized in vitro; however, studies of their functional in vivo effects have been limited. The current report compares the effects of homobivalent ligand CJL-1-87, Ac-His-DPhe-Arg-Trp-PEDG20-His-DPhe-Arg-Trp-NH 2 , to monovalent ligand CJL-1-14, Ac-His-DPhe-Arg-Trp-NH 2 , on energy homeostasis in mice after central intracerebroventricular (ICV) administration into the lateral ventricle of the brain. Bivalent ligand CJL-1-87 had noteworthy advantages as an antiobesity probe over CJL-1-14 in a fasting-refeeding in vivo paradigm. Treatment with CJL-1-87 significantly decreased food intake compared to CJL-1-14 or saline (50% less intake 2-8 h after treatment). Furthermore, CJL-1-87 treatment decreased the respiratory exchange ratio (RER) without changing the energy expenditure indicating that fats were being burned as the primary fuel source. Additionally, CJL-1-87 treatment significantly lowered body fat mass percentage 6 h after administration (p < 0.05) without changing the lean mass percentage. The bivalent ligand significantly decreased insulin, C-peptide, leptin, GIP, and resistin plasma levels compared to levels after CJL-1-14 or saline treatments. Alternatively, ghrelin plasma levels were significantly increased. Serum stability of CJL-1-87 and CJL-1-14 (T 1/2 = 6.0 and 16.8 h, respectively) was sufficient to permit physiological effects. The differences in binding affinity of CJL-1-14 compared to CJL-1-87 are speculated as a possible mechanism for the bivalent ligand's unique effects. We also provide in vitro evidence for the formation of a MC3R-MC4R heterodimer complex, for the first time to our knowledge, that may be an unexploited neuronal molecular target. Regardless of the exact mechanism, the advantageous ability of CJL-1-87 compared to CJL-1-14 to increase in vitro binding affinity, increase the duration of action in spite of decreased serum stability, decrease

  16. Development and installation of solution measurement and monitoring system (SMMS) at TRP

    International Nuclear Information System (INIS)

    Satoh, Takehiko; Yamanaka, Atsushi; Kashimura, Takao; Yamamoto, Tokuhiro

    2001-01-01

    The IAEA proposed TRP safeguard improvement plants in 1995 for closer and more efficient safeguards of TRP. Development of Solution Measurement and Monitoring System (SMMS) is one item of the plans and has been carried out under the JASPAS program as JA-6. Following to the IAEA's acceptance test, after the installation of the SMMS in 1999, field test of this system has been carried out. The main purpose of the SMMS is to establish the IAEA's independent monitoring system. Besides input and output accountability tanks, seven Pu storage tanks and a pot attached to the Pu storage tanks are monitored continuously, and solution level, density and temperature data of these tanks are recorded by the SMMS. Authentication of the SMMS, confirmed by the IAEA at the acceptance test, is kept by failure detection and recording functions of the system. (author)

  17. Properties of the intracellular transient receptor potential (TRP) channel in yeast, Yvc1.

    Science.gov (United States)

    Chang, Yiming; Schlenstedt, Gabriel; Flockerzi, Veit; Beck, Andreas

    2010-05-17

    Transient receptor potential (TRP) channels are found among mammals, flies, worms, ciliates, Chlamydomonas, and yeast but are absent in plants. These channels are believed to be tetramers of proteins containing six transmembrane domains (TMs). Their primary structures are diverse with sequence similarities only in some short amino acid sequence motifs mainly within sequences covering TM5, TM6, and adjacent domains. In the yeast genome, there is one gene encoding a TRP-like sequence. This protein forms an ion channel in the vacuolar membrane and is therefore called Yvc1 for yeast vacuolar conductance 1. In the following we summarize its prominent features. Copyright 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  18. A kinetic model of trp-cage folding from multiple biased molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Fabrizio Marinelli

    2009-08-01

    Full Text Available Trp-cage is a designed 20-residue polypeptide that, in spite of its size, shares several features with larger globular proteins.Although the system has been intensively investigated experimentally and theoretically, its folding mechanism is not yet fully understood. Indeed, some experiments suggest a two-state behavior, while others point to the presence of intermediates. In this work we show that the results of a bias-exchange metadynamics simulation can be used for constructing a detailed thermodynamic and kinetic model of the system. The model, although constructed from a biased simulation, has a quality similar to those extracted from the analysis of long unbiased molecular dynamics trajectories. This is demonstrated by a careful benchmark of the approach on a smaller system, the solvated Ace-Ala3-Nme peptide. For theTrp-cage folding, the model predicts that the relaxation time of 3100 ns observed experimentally is due to the presence of a compact molten globule-like conformation. This state has an occupancy of only 3% at 300 K, but acts as a kinetic trap.Instead, non-compact structures relax to the folded state on the sub-microsecond timescale. The model also predicts the presence of a state at Calpha-RMSD of 4.4 A from the NMR structure in which the Trp strongly interacts with Pro12. This state can explain the abnormal temperature dependence of the Pro12-delta3 and Gly11-alpha3 chemical shifts. The structures of the two most stable misfolded intermediates are in agreement with NMR experiments on the unfolded protein. Our work shows that, using biased molecular dynamics trajectories, it is possible to construct a model describing in detail the Trp-cage folding kinetics and thermodynamics in agreement with experimental data.

  19. Expression and distribution of transient receptor potential (TRP) channels in bladder epithelium.

    Science.gov (United States)

    Yu, Weiqun; Hill, Warren G; Apodaca, Gerard; Zeidel, Mark L

    2011-01-01

    The urothelium is proposed to be a sensory tissue that responds to mechanical stress by undergoing dynamic membrane trafficking and neurotransmitter release; however, the molecular basis of this function is poorly understood. Transient receptor potential (TRP) channels are ideal candidates to fulfill such a role as they can sense changes in temperature, osmolarity, and mechanical stimuli, and several are reported to be expressed in the bladder epithelium. However, their complete expression profile is unknown and their cellular localization is largely undefined. We analyzed expression of all 33 TRP family members in mouse bladder and urothelium by RT-PCR and found 22 specifically expressed in the urothelium. Of the latter, 10 were chosen for closer investigation based on their known mechanosensory or membrane trafficking functions in other cell types. Western blots confirmed urothelial expression of TRPC1, TRPC4, TRPV1, TRPV2, TRPV4, TRPM4, TRPM7, TRPML1, and polycystins 1 and 2 (PKD1 and PKD2) proteins. We further defined the cellular and subcellular localization of all 10 TRP channels. TRPV2 and TRPM4 were prominently localized to the umbrella cell apical membrane, while TRPC4 and TRPV4 were identified on their abluminal surfaces. TRPC1, TRPM7, and TRPML1 were localized to the cytoplasm, while PKD1 and PKD2 were expressed on the apical and basolateral membranes of umbrella cells as well as in the cytoplasm. The cellular location of TRPV1 in the bladder has been debated, but colocalization with neuronal marker calcitonin gene-related peptide indicated clearly that it is present on afferent neurons that extend into the urothelium, but may not be expressed by the urothelium itself. These findings are consistent with the hypothesis that the urothelium acts as a sentinel and by expressing multiple TRP channels it is likely it can detect and presumably respond to a diversity of external stimuli and suggest that it plays an important role in urothelial signal

  20. Theoretical evaluation of transcriptional pausing effect on the attenuation in trp leader sequence

    OpenAIRE

    Suzuki, H.; Kunisawa, T.; Otsuka, J.

    1986-01-01

    The effect of transcriptional pausing on attenuation is investigated theoretically on the basis of the attenuation control mechanism presented by Oxender et al. (Oxender, D. L., G. Zurawski, and C. Yanofsky, 1979, Proc. Natl. Acad. Sci. USA. 76:5524-5528). An extended stochastic model including the RNA polymerase pausing in the leader region is developed to calculate the probability of relative position between the RNA polymerase transcribing the trp leader sequence and the ribosome translati...

  1. Relationship between ADD1 Gly460Trp gene polymorphism and essential hypertension in Madeira Island.

    Science.gov (United States)

    Sousa, Ana Célia; Palma Dos Reis, Roberto; Pereira, Andreia; Borges, Sofia; Freitas, Ana Isabel; Guerra, Graça; Góis, Teresa; Rodrigues, Mariana; Henriques, Eva; Freitas, Sónia; Ornelas, Ilídio; Pereira, Décio; Brehm, António; Mendonça, Maria Isabel

    2017-10-01

    Essential hypertension (EH) is a complex disease in which physiological, environmental, and genetic factors are involved in its genesis. The genetic variant of the alpha-adducin gene (ADD1) has been described as a risk factor for EH, but with controversial results.The objective of this study was to evaluate the association of ADD1 (Gly460Trp) gene polymorphism with the EH risk in a population from Madeira Island.A case-control study with 1614 individuals of Caucasian origin was performed, including 817 individuals with EH and 797 controls. Cases and controls were matched for sex and age, by frequency-matching method. All participants collected blood for biochemical and genotypic analysis for the Gly460Trp polymorphism. We further investigated which variables were independently associated to EH, and, consequently, analyzed their interactions.In our study, we found a significant association between the ADD1 gene polymorphism and EH (odds ratio 2.484, P = .01). This association remained statistically significant after the multivariate analysis (odds ratio 2.548, P = .02).The ADD1 Gly460Trp gene polymorphism is significantly and independently associated with EH risk in our population. The knowledge of genetic polymorphisms associated with EH is of paramount importance because it leads to a better understanding of the etiology and pathophysiology of this pathology.

  2. TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons

    Directory of Open Access Journals (Sweden)

    Yong Gao

    2017-01-01

    Full Text Available The molecular mechanisms underlying acute leptin and serotonin 2C receptor-induced hypophagia remain unclear. Here, we show that neuronal and pro-opiomelanocortin (Pomc-specific loss of transient receptor potential cation 5 (TrpC5 subunits is sufficient to decrease energy expenditure and increase food intake resulting in elevated body weight. Deficiency of Trpc5 subunits in Pomc neurons is also sufficient to block the anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr agonists. The loss of acute anorexigenic effects of these receptors is concomitant with a blunted electrophysiological response to both leptin and Ht2Cr agonists in arcuate Pomc neurons. We also demonstrate that the Ht2Cr agonist lorcaserin-induced improvements in glucose and insulin tolerance are blocked by TrpC5 deficiency in Pomc neurons. Together, our results link TrpC5 subunits in the brain with leptin- and serotonin 2C receptor-dependent changes in neuronal activity, as well as energy balance, feeding behavior, and glucose metabolism.

  3. Functional TRP and ASIC-like channels in cultured urothelial cells from the rat.

    Science.gov (United States)

    Kullmann, F Aura; Shah, M A; Birder, L A; de Groat, W C

    2009-04-01

    Transient receptor potential (TRP) and acid-sensing ion channels (ASIC) are molecular detectors of chemical, mechanical, thermal, and nociceptive stimuli in sensory neurons. They have been identified in the urothelium, a tissue considered part of bladder sensory pathways, where they might play a role in bladder function. This study investigated functional properties of TRP and ASIC channels in cultured urothelial cells from the rat using patch-clamp and fura 2 Ca(2+) imaging techniques. The TRPV4 agonist 4alpha-phorbol-12,13 didecanoate (4alpha-PDD; 1-5 microM) and the TRPA1/TRPM8 agonist icilin (50-100 microM) elicited transient currents in a high percentage of cells (>70%). 4alpha-PDD responses were suppressed by the TRPV4 antagonist HC-010961 (10 microM). The TRPV1 agonist capsaicin (1-100 microM) and the TRPA1/TRPM8 agonist menthol (5-200 microM) elicited transient currents in a moderate percentage of cells ( approximately 25%). All of these agonists increased intracellular calcium concentration ([Ca(2+)](i)). Most cells responded to more than one TRP agonist (e.g., capsaicin and 4alpha-PDD), indicating coexpression of different TRP channels. In the presence of the TRPV1 antagonist capsazepine (10 microM), changes in pH induced by HCl elicited ionic currents (pH 5.5) and increased [Ca(2+)](i) (pH 6.5) in approximately 50% of cells. Changes in pH using acetic acid (pH 5.5) elicited biphasic-like currents. Responses induced by acid were sensitive to amiloride (10 microM). In summary, urothelial cells express multiple TRP and ASIC channels, whose activation elicits ionic currents and Ca(2+) influx. These "neuron-like" properties might be involved in transmitter release, such as ATP, that can act on afferent nerves or smooth muscle to modulate their responses to different stimuli.

  4. Projectables

    DEFF Research Database (Denmark)

    Rasmussen, Troels A.; Merritt, Timothy R.

    2017-01-01

    CNC cutting machines have become essential tools for designers and architects enabling rapid prototyping, model-building and production of high quality components. Designers often cut from new materials, discarding the irregularly shaped remains. We introduce ProjecTables, a visual augmented...... reality system for interactive packing of model parts onto sheet materials. ProjecTables enables designers to (re)use scrap materials for CNC cutting that would have been previously thrown away, at the same time supporting aesthetic choices related to wood grain, avoiding surface blemishes, and other...... relevant material properties. We conducted evaluations of ProjecTables with design students from Aarhus School of Architecture, demonstrating that participants could quickly and easily place and orient model parts reducing material waste. Contextual interviews and ideation sessions led to a deeper...

  5. Radiolabelled neurotensin analogues. I. Solid phase synthesis and biological characterization of [Trp11]-neurotensin precursor of an ionidated ligand

    International Nuclear Information System (INIS)

    Labbe-Jullie, C.; Granier, C.; Van Rietschoten, J.; Kitabgi, P.; Vincent, J.P.

    1983-01-01

    In order to generate highly labelled neurotensin analogues, synthesis has been performed of two types of precursors, one for iodination and one for tritiation. Iodination of native neurotensin occurs on both tyrosines in position 3 and 11 and thus affects greatly its binding capacities. Synthesis and chemical characterization of [Trp 11 ]-neurotensin are described which can be iodinated without loss of activity. Synthesis was by solid phase procedure on an experimental support, Pab-resin, α-(4-chloromethylphenylacetamido)-benzyl copoly (styrene 1 per cent divinylbenzene). The homogeneity of [Trp 11 ]-neurotensin was assessed by amino acid analysis, high voltage paper electrophoresis and high pressure liquid chromatography. Iodination by the lactoperoxydase method gave iodo-[Trp 11 ]-neurotensin iodinated on the Tyr 3 . Compared to neurotensin, potency of [Trp 11 ]-neurotensin and of iodo-[Trp 11 ]-neurotensin in competitive inhibition of tritiated neurotensin binding to rat brain synaptic membranes was respectively 93 per cent and 80 per cent, but in the biological test on the contractility of isolated longitudinal smooth muscle strips of guinea pig the relative activity for the two analogues was of 10 per cent [fr

  6. Regulation of His-dTrp-Ala-Trp-dPhe-Lys-NH2 (GHRP-6)-induced GH secretion in the rat.

    Science.gov (United States)

    Mallo, F; Alvarez, C V; Benitez, L; Burguera, B; Coya, R; Casanueva, F F; Dieguez, C

    1993-01-01

    His-dTrp-Ala-Trp-dPhe,Lys-NH2(GHRP-6) is a synthetic compound that releases GH in a dose-response and specific manner in several species and that may well be related to an endogenous compound of similar structure. The aim of this study was to investigate the in vivo GH responses to GHRP-6 in pentobarbital anesthetized rats. Specifically and in order to avoid the influence of endogenous GHRH and somatostatin secretion we studied the GH responses to GHRP-6 in animals with surgical ablation of the hypothalamus, confirmed by histological assessment, as well as in hypophysectomyzed-transplanted rats bearing two hypophyses under the renal capsule. Since it has been previously reported that rats pretreated with GHRH (10 micrograms/kg i.p. every 12 h for 15 days) rather than saline-treated rats have greater GH responses to acutely administered GHRH, we compared the self-potentiating effect of chronic GH pretreatment with GHRP-6 (10 micrograms/kg i.p. every 12 h). Furthermore we also studied the influence of estrogens, glucocorticoids, free fatty acids (FFA) and bombesin on somatotroph responsiveness to GHRP-6 in intact rats. We found a greater GH response to GHRP-6 in rats that underwent a surgical ablation of the hypothalamus 36 h prior to the test than in sham-operated rats. A direct stimulatory effect of GHRP-6 on in vivo GH secretion was demonstrated by a clear GH response to GHRP-6 in hypophysectomyzed-transplanted rats. In addition, we found a similar response whether the animals were pretreated with GHRH or GHRP-6 over the previous 2 weeks. Finally, we found that both estrogen- and testosterone-treated rats have greater GH responses to GHRP-6 than untreated rats. On the other hand, chronic dexamethasone administration, acute elevation of circulating FFA levels and bombesin administration markedly inhibited GH responses to GHRP-6. In contrast to the effects exerted on GH responses to GHRP-6 estrogen administration led to a decrease in GH responses to GHRH while

  7. Audit Report on "The Department of Energy's American Recovery and Reinvestment Act -- Florida State Energy Program"

    Energy Technology Data Exchange (ETDEWEB)

    None

    2010-06-01

    The Department of Energy's Office of Energy Efficiency and Renewable Energy (EERE) provides grants to states, territories, and the District of Columbia to support their energy priorities through the State Energy Program (SEP). The SEP provides Federal financial assistance to carry out energy efficiency and renewable energy projects that meet each state's unique energy needs while also addressing national goals such as energy security. Federal funding is based on a grant formula that takes into account population and energy consumption. The SEP emphasizes the state's role as the decision maker and administrator for the program. The American Recovery and Reinvestment Act of 2009 (Recovery Act) expanded the SEP, authorizing $3.1 billion in grants. Based on existing grant formulas and after reviewing state-level plans, EERE made awards to states. The State of Florida's Energy Office (Florida) was allocated $126 million - a 90-fold increase over Florida's average annual SEP grant of $1.4 million. Per the Recovery Act, this funding must be obligated by September 30, 2010, and spent by April 30, 2012. As of March 10, 2010, Florida had expended $13.2 million of the SEP Recovery Act funds. Florida planned to use its grant funds to undertake activities that would preserve and create jobs; save energy; increase renewable energy sources; and, reduce greenhouse gas emissions. To accomplish Recovery Act objectives, states could either fund new or expand existing projects. As a condition of the awards, EERE required states to develop and implement sound internal controls over the use of Recovery Act funds. Based on the significant increase in funding from the Recovery Act, we initiated this review to determine whether Florida had internal controls in place to provide assurance that the goals of the SEP and Recovery Act will be met and accomplished efficiently and effectively. We identified weaknesses in the implementation of SEP Recovery Act projects that

  8. Special Report "The American Recovery and Reinvestment Act and the Department of Energy"

    Energy Technology Data Exchange (ETDEWEB)

    None

    2009-03-01

    The American Recovery and Reinvestment Act of 2009 (Recovery Act) was signed into law on February 17, 2009, as a way to jumpstart the U.S. economy, create or save millions of jobs, spur technological advances in science and health, and invest in the Nation's energy future. This national effort will require an unprecedented level of transparency and accountability to ensure that U.S. citizens know where their tax dollars are going and how they are being spent. As part of the Recovery Act, the Department of Energy will receive more than $38 billion to support a number of science, energy, and environmental initiatives. Additionally, the Department's authority to make or guarantee energy-related loans has increased to about $127 billion. The Department plans to disburse the vast majority of the funds it receives through grants, cooperative agreements, contracts, and other financial instruments. The supplemental funding provided to the Department of Energy under the Recovery Act dwarfs the Department's annual budget of about $27 billion. The infusion of these funds and the corresponding increase in effort required to ensure that they are properly controlled and disbursed in a timely manner will, without doubt, strain existing resources. It will also have an equally challenging impact on the inherent risks associated with operating the Department's sizable portfolio of missions and activities and, this is complicated by the fact that, in many respects, the Recovery Act requirements represent a fundamental transformation of the Department's mission. If these challenges are to be met successfully, all levels of the Department's structure and its many constituents, including the existing contractor community; the national laboratory system; state and local governments; community action groups and literally thousands of other contract, grant, loan and cooperative agreement recipients throughout the Nation will have to strengthen existing or

  9. Justice Reinvestment: “Motherhood and Apple Pie?”—Matching Ambition to Capacity and Capability

    OpenAIRE

    Wong, Kevin; Christmann, Kris

    2016-01-01

    The idea of '“Justice Reinvestment'” (JR), has been proposed by United Kingdom (UK) policy makers and criminal justice campaigners as a way of responding to the problems arising from the economic crisis in 2007 and 2008. Despite the interest in JR from policy makers, a systematic approach to JR in the UK has yet to be adopted. Instead, the implementation of JR in the UK has been limited to a somewhat piecemeal approach with an uncoordinated set of initiatives, including Payment by Results (Pb...

  10. Acid-base titration of melanocortin peptides: evidence of Trp rotational conformers interconversion.

    Science.gov (United States)

    Fernandez, Roberto M; Vieira, Renata F F; Nakaie, Clóvis R; Lamy, M Teresa; Ito, Amando S

    2005-01-01

    Tryptophantime-resolved fluorescence was used to monitor acid-base titration properties of alpha-melanocyte stimulating hormone (alpha-MSH) and the biologically more potent analog [Nle4, D-Phe7]alpha -MSH (NDP-MSH), labeled or not with the paramagnetic amino acid probe 2,2,6,6-tetramthylpiperidine-N-oxyl-4-amino-4-carboxylic acid (Toac). Global analysis of fluorescence decay profiles measured in the pH range between 2.0 and 11.0 showed that, for each peptide, the data could be well fitted to three lifetimes whose values remained constant. The less populated short lifetime component changed little with pH and was ascribed to Trp g+ chi1 rotamer, in which electron transfer deactivation predominates over fluorescence. The long and intermediate lifetime preexponential factors interconverted along that pH interval and the result was interpreted as due to interconversion between Trp g- and trans chi1 rotamers, driven by conformational changes promoted by modifications in the ionization state of side-chain residues. The differences in the extent of interconversion in alpha-MSH and NDP-MSH are indicative of structural differences between the peptides, while titration curves suggest structural similarities between each peptide and its Toac-labeled species, in aqueous solution. Though less sensitive than fluorescence, the Toac electron spin resonance (ESR) isotropic hyperfine splitting parameter can also monitor the titration of side-chain residues located relatively far from the probe. Copyright (c) 2005 Wiley Periodicals, Inc.

  11. TRP channels and traffic-related environmental pollution-induced pulmonary disease.

    Science.gov (United States)

    Akopian, Armen N; Fanick, E Robert; Brooks, Edward G

    2016-05-01

    Environmental pollutant exposures are major risk factors for adverse health outcomes, with increased morbidity and mortality in humans. Diesel exhaust (DE) is one of the major harmful components of traffic-related air pollution. Exposure to DE affects several physiological systems, including the airways, and pulmonary diseases are increased in highly populated urban areas. Hence, there are urgent needs to (1) create newer and lesser polluting fuels, (2) improve exhaust aftertreatments and reduce emissions, and (3) understand mechanisms of actions for toxic effects of both conventional and cleaner diesel fuels on the lungs. These steps could aid the development of diagnostics and interventions to prevent the negative impact of traffic-related air pollution on the pulmonary system. Exhaust from conventional, and to a lesser extent, clean fuels, contains particulate matter (PM) and more than 400 additional chemical constituents. The major toxic constituents are nitrogen oxides (NOx) and polycyclic aromatic hydrocarbons (PAHs). PM and PAHs could potentially act via transient receptor potential (TRP) channels. In this review, we will first discuss the associations between DE from conventional as well as clean fuel technologies and acute and chronic airway inflammation. We will then review possible activation and/or potentiation of TRP vanilloid type 1 (TRPV1) and ankyrin 1 (TRPA1) channels by PM and PAHs. Finally, we will discuss and summarize recent findings on the mechanisms whereby TRPs could control the link between DE and airway inflammation, which is a primary determinant leading to pulmonary disease.

  12. Ehrlichia chaffeensis TRP120 Activates Canonical Notch Signaling To Downregulate TLR2/4 Expression and Promote Intracellular Survival

    Directory of Open Access Journals (Sweden)

    Taslima T. Lina

    2016-07-01

    Full Text Available Ehrlichia chaffeensis preferentially targets mononuclear phagocytes and survives through a strategy of subverting innate immune defenses, but the mechanisms are unknown. We have shown E. chaffeensis type 1 secreted tandem repeat protein (TRP effectors are involved in diverse molecular pathogen-host interactions, such as the TRP120 interaction with the Notch receptor-cleaving metalloprotease ADAM17. In the present study, we demonstrate E. chaffeensis, via the TRP120 effector, activates the canonical Notch signaling pathway to promote intracellular survival. We found that nuclear translocation of the transcriptionally active Notch intracellular domain (NICD occurs in response to E. chaffeensis or recombinant TRP120, resulting in upregulation of Notch signaling pathway components and target genes notch1, adam17, hes, and hey. Significant differences in canonical Notch signaling gene expression levels (>40% were observed during early and late stages of infection, indicating activation of the Notch pathway. We linked Notch pathway activation specifically to the TRP120 effector, which directly interacts with the Notch metalloprotease ADAM17. Using pharmacological inhibitors and small interfering RNAs (siRNAs against γ-secretase enzyme, Notch transcription factor complex, Notch1, and ADAM17, we demonstrated that Notch signaling is required for ehrlichial survival. We studied the downstream effects and found that E. chaffeensis TRP120-mediated activation of the Notch pathway causes inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2 and p38 mitogen-activated protein kinase (MAPK pathways required for PU.1 and subsequent Toll-like receptor 2/4 (TLR2/4 expression. This investigation reveals a novel mechanism whereby E. chaffeensis exploits the Notch pathway to evade the host innate immune response for intracellular survival.

  13. Arg753gln and Arg677 Trp Polymorphisms of Toll-Like Receptor 2 In Acute Apical Abscess.

    Science.gov (United States)

    Miri-Moghaddam, Ebrahim; Farhad Mollashahi, Narges; Naghibi, Nava; Garme, Yasaman; Bazi, Ali

    2018-06-01

    Genetic polymorphisms can alter immunity response against pathogens, which in turn influence individuals' susceptibility to certain infections. Our aim was to determine the association of Arg753Gln (rs5743708) and Arg677Trp (rs12191786) polymorphisms of toll like receptor-2 gene with the two clinical forms of apical periodontitis: acute apical abscess (AAA) and asymptomatic apical periodontitis (AAP). There were 50 patients with AAA as case group and 50 with AAP as control group. Genotyping was done using Tetra-ARMS (amplification refractory mutation system) PCR. Heterozygous genotype of Arg677Trp polymorphism was associated with risk of AAA (OR=1.9, 95% CI: 0.7-5.5, p = 0.05). Although statistically insignificant, Arg677Trp polymorphism promoted the risk of AAA in dominant model (OR=2.1, 95% CI: 0.7-5.9, p > 0.05). The frequency of mutant allele (T) of Arg677Trp polymorphism was higher in AAA (14%) than AAP (7%) subjects (OR=1.7, 95% CI: 0.6-4.7). For Arg753Gln polymorphism, wild homozygous (GG) represented the dominant genotype in both cases (96%) and controls (100%). Variant allele (A) of Arg753Gln polymorphism was identified in 2% of AAA, while no individual represented with this allele in AAP subjects. Individuals with Arg753Gln; Arg677Trp (GG; TC) combination showed an elevated risk of AAA (OR=1.6, 95% CI: 0.5- 4.2, p > 0.05). Arg677Trp polymorphism of TLR-2 rendered a higher risk for the development of abscesses in apical periodontitis. It is recommended to explore role of this polymorphism in other populations.

  14. XRCC1 Arg194Trp and Arg399Gln polymorphisms and arsenic methylation capacity are associated with urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, Chien-I [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Huang, Ya-Li [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Chen, Wei-Jen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (China); Huang, Chao-Yuan; Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Lin, Ying-Chin [Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, New Taipei, Taiwan (China); Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan (China); Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2014-09-15

    The association between DNA repair gene polymorphisms and bladder cancer has been widely studied. However, few studies have examined the correlation between urothelial carcinoma (UC) and arsenic or its metabolites. The aim of this study was to examine the association between polymorphisms of the DNA repair genes, XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln, with urinary arsenic profiles and UC. To this end, we conducted a hospital-based case–control study with 324 UC patients and 647 age- and gender-matched non-cancer controls. Genomic DNA was used to examine the genotype of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln by PCR-restriction fragment length polymorphism analysis (PCR-RFLP). Urinary arsenic profiles were measured by high performance liquid chromatography (HPLC) linked with hydride generator and atomic absorption spectrometry. The XRCC1 399 Gln/Gln and 194 Arg/Trp and Trp/Trp genotypes were significantly related to UC, and the odds ratio (OR) and 95% confidence interval (95%CI) were 1.68 (1.03–2.75) and 0.66 (0.48–0.90), respectively. Participants with higher total urinary arsenic levels, a higher percentage of inorganic arsenic (InAs%) and a lower percentage of dimethylarsinic acid (DMA%) had a higher OR of UC. Participants carrying XRCC1 risk diplotypes G-C/G-C, A-C/A-C, and A-T/G-T, and who had higher total arsenic levels, higher InAs%, or lower DMA% compared to those with other XRCC1 diplotypes had a higher OR of UC. Our results suggest that the XRCC1 399 Gln/Gln and 194 Arg/Arg DNA repair genes play an important role in poor arsenic methylation capacity, thereby increasing the risk of UC in non-obvious arsenic exposure areas. - Highlights: • The XRCC1 399Gln/Gln genotype was significantly associated with increased OR of UC. • The XRCC1 194 Arg/Trp and Trp/Trp genotype had a significantly decreased OR of UC. • Combined effect of the XRCC1 genotypes and poor arsenic methylation capacity on

  15. Loss of Cdh1 and Trp53 in the uterus induces chronic inflammation with modification of tumor microenvironment.

    Science.gov (United States)

    Stodden, G R; Lindberg, M E; King, M L; Paquet, M; MacLean, J A; Mann, J L; DeMayo, F J; Lydon, J P; Hayashi, K

    2015-05-07

    Type II endometrial carcinomas (ECs) are estrogen independent, poorly differentiated tumors that behave in an aggressive manner. As TP53 mutation and CDH1 inactivation occur in 80% of human endometrial type II carcinomas, we hypothesized that mouse uteri lacking both Trp53 and Cdh1 would exhibit a phenotype indicative of neoplastic transformation. Mice with conditional ablation of Cdh1 and Trp53 (Cdh1(d/d)Trp53(d/d)) clearly demonstrate architectural features characteristic of type II ECs, including focal areas of papillary differentiation, protruding cytoplasm into the lumen (hobnailing) and severe nuclear atypia at 6 months of age. Further, Cdh1(d/d)Trp53(d/d) tumors in 12-month-old mice were highly aggressive, and metastasized to nearby and distant organs within the peritoneal cavity, such as abdominal lymph nodes, mesentery and peri-intestinal adipose tissues, demonstrating that tumorigenesis in this model proceeds through the universally recognized morphological intermediates associated with type II endometrial neoplasia. We also observed abundant cell proliferation and complex angiogenesis in the uteri of Cdh1(d/d)Trp53(d/d) mice. Our microarray analysis found that most of the genes differentially regulated in the uteri of Cdh1(d/d)Trp53(d/d) mice were involved in inflammatory responses. CD163 and Arg1, markers for tumor-associated macrophages, were also detected and increased in the uteri of Cdh1(d/d)Trp53(d/d) mice, suggesting that an inflammatory tumor microenvironment with immune cell recruitment is augmenting tumor development in Cdh1(d/d)Trp53(d/d) uteri. Further, inflammatory mediators secreted from CDH1-negative, TP53 mutant endometrial cancer cells induced normal macrophages to express inflammatory-related genes through activation of nuclear factor-κB signaling. These results indicate that absence of CDH1 and TP53 in endometrial cells initiates chronic inflammation, promotes tumor microenvironment development following the recruitment of macrophages

  16. Meta-analysis of the association between the Trp64Arg polymorphism of the beta-3 adrenergic receptor and susceptibility to gestational diabetes mellitus.

    Science.gov (United States)

    Guan, Lianyue; Cui, Xiaofeng; Zhou, Hui

    2018-02-01

    The study aimed to explore the associations between Trp64Arg polymorphism of Beta-3 Adrenergic receptor (ADRB3) and susceptibility to gestational diabetes mellitus (GDM). Relevant studies till December 2013 were identified through searching electronic databases. A meta-analysis was conducted on associations between Trp64Arg polymorphism in ADRB3 and susceptibility to GDM. We found no association between Trp64Arg polymorphism in ADRB3 and susceptibility to GDM in overall population (Arg vs. Trp: OR = 1.20, 95%CI = 0.99-1.47, p = .16; Trp/Arg + Arg/Arg vs. Trp/Trp: OR = 1.22, 95%CI = 0.99-1.50, p = .11). In subgroup analysis on European Caucasian population, Trp64Arg in ADRB3 was associated with susceptibility to GDM. Trp64Arg polymorphism in ADRB3 had certain association with susceptibility to GDM in the European Caucasian population. Impact statement What is already known on this subject: Gestational diabetes mellitus (GDM) is recognised as carbohydrate intolerance of varied severity that begins or is first recognised during pregnancy. A missense mutation in the codon 64 of the Beta-3 adrenergic receptor (ADRB3), Trp64Arg, leads to the substitution of tryptophan by arginine in the first intracellular loop of the ADRB3 receptor. Trp64Arg Polymorphism has also been reportedly associated with increased body weight, type 2 diabetes mellitus, insulin resistance and obesity. However, other investigators have found that the Trp64Arg polymorphism of ADRB3 has no effect on insulin resistance, obesity or type 2 diabetes mellitus. What the results of the study add: Our present meta-analysis demonstrated that Trp64Arg polymorphism in ADRB3 was associated with susceptibility to GDM in the European Caucasian population. Trp64Arg polymorphism in ADRB3 may be able to predict the occurrence of GDM and used for the diagnosis of it in clinic. What the implications are of these findings for clinical practice and future research: The findings in this study

  17. The Transient Receptor Potential (TRP) Channel Family in Colletotrichum graminicola: A Molecular and Physiological Analysis.

    Science.gov (United States)

    Lange, Mario; Weihmann, Fabian; Schliebner, Ivo; Horbach, Ralf; Deising, Holger B; Wirsel, Stefan G R; Peiter, Edgar

    2016-01-01

    Calcium (Ca2+) is a universal second messenger in all higher organisms and centrally involved in the launch of responses to environmental stimuli. Ca2+ signals in the cytosol are initiated by the activation of Ca2+ channels in the plasma membrane and/or in endomembranes. Yeast (Saccharomyces cerevisiae) contains a Ca2+-permeable channel of the TRP family, TRPY1, which is localized in the vacuolar membrane and contributes to cytosolic free Ca2+ ([Ca2+]cyt) elevations, for example in response to osmotic upshock. A TRPY1 homologue in the rice blast fungus is known to be important for growth and pathogenicity. To determine the role of the TRP channel family in the maize pathogen Colletotrichum graminicola, proteins homologous to TRPY1 were searched. This identified not one, but four genes in the C. graminicola genome, which had putative orthologs in other fungi, and which we named CgTRPF1 through 4. The topology of the CgTRPF proteins resembled that of TRPY1, albeit with a variable number of transmembrane (TM) domains additional to the six-TM-domain core and a diverse arrangement of putatively Ca2+-binding acidic motifs. All CgTRPF genes were expressed in axenic culture and throughout the infection of maize. Like TRPY1, all TRPF proteins of C. graminicola were localized intracellularly, albeit three of them were found not in large vacuoles, but co-localized in vesicular structures. Deletion strains for the CgTRPF genes were not altered in processes thought to involve Ca2+ release from internal stores, i.e. spore germination, the utilization of complex carbon sources, and the generation of tip-focussed [Ca2+]cyt spikes. Heterologous expression of CgTRPF1 through 4 in a tryp1Δ yeast mutant revealed that none of the channels mediated the release of Ca2+ in response to osmotic upshock. Accordingly, aequorin-based [Ca2+]cyt measurements of C. graminicola showed that in this fungus, osmotic upshock-triggered [Ca2+]cyt elevations were generated entirely by influx of Ca2

  18. The Transient Receptor Potential (TRP Channel Family in Colletotrichum graminicola: A Molecular and Physiological Analysis.

    Directory of Open Access Journals (Sweden)

    Mario Lange

    Full Text Available Calcium (Ca2+ is a universal second messenger in all higher organisms and centrally involved in the launch of responses to environmental stimuli. Ca2+ signals in the cytosol are initiated by the activation of Ca2+ channels in the plasma membrane and/or in endomembranes. Yeast (Saccharomyces cerevisiae contains a Ca2+-permeable channel of the TRP family, TRPY1, which is localized in the vacuolar membrane and contributes to cytosolic free Ca2+ ([Ca2+]cyt elevations, for example in response to osmotic upshock. A TRPY1 homologue in the rice blast fungus is known to be important for growth and pathogenicity. To determine the role of the TRP channel family in the maize pathogen Colletotrichum graminicola, proteins homologous to TRPY1 were searched. This identified not one, but four genes in the C. graminicola genome, which had putative orthologs in other fungi, and which we named CgTRPF1 through 4. The topology of the CgTRPF proteins resembled that of TRPY1, albeit with a variable number of transmembrane (TM domains additional to the six-TM-domain core and a diverse arrangement of putatively Ca2+-binding acidic motifs. All CgTRPF genes were expressed in axenic culture and throughout the infection of maize. Like TRPY1, all TRPF proteins of C. graminicola were localized intracellularly, albeit three of them were found not in large vacuoles, but co-localized in vesicular structures. Deletion strains for the CgTRPF genes were not altered in processes thought to involve Ca2+ release from internal stores, i.e. spore germination, the utilization of complex carbon sources, and the generation of tip-focussed [Ca2+]cyt spikes. Heterologous expression of CgTRPF1 through 4 in a tryp1Δ yeast mutant revealed that none of the channels mediated the release of Ca2+ in response to osmotic upshock. Accordingly, aequorin-based [Ca2+]cyt measurements of C. graminicola showed that in this fungus, osmotic upshock-triggered [Ca2+]cyt elevations were generated entirely by

  19. TRP channels in brown and white adipogenesis from human progenitors : new therapeutic targets and the caveats associated with the common antibiotic, streptomycin

    NARCIS (Netherlands)

    Goralczyk, A.; van Vijven, M.; Koch, M.; Badowski, C.; Yassin, M.S.; Toh, S.A.; Shabbir, A.; Franco-Obregón, A.; Raghunath, M.

    2017-01-01

    Transient receptor potential (TRP) channels are polymodal cell sensors responding to diverse stimuli and widely implicated in the developmental programs of numerous tissues. The evidence for an involvement of TRP family members in adipogenesis, however, is scant. We present the first comprehensive

  20. Improved Synthesis of 4-Cyanotryptophan and Other Tryptophan Analogues in Aqueous Solvent Using Variants of TrpB from Thermotoga maritima.

    Science.gov (United States)

    Boville, Christina E; Romney, David K; Almhjell, Patrick J; Sieben, Michaela; Arnold, Frances H

    2018-04-27

    The use of enzymes has become increasingly widespread in synthesis as chemists strive to reduce their reliance on organic solvents in favor of more environmentally benign aqueous media. With this in mind, we previously endeavored to engineer the tryptophan synthase β-subunit (TrpB) for production of noncanonical amino acids that had previously been synthesized through multistep routes involving water-sensitive reagents. This enzymatic platform proved effective for the synthesis of analogues of the amino acid tryptophan (Trp), which are frequently used in pharmaceutical synthesis as well as chemical biology. However, certain valuable compounds, such as the blue fluorescent amino acid 4-cyanotryptophan (4-CN-Trp), could only be made in low yield, even at elevated temperature (75 °C). Here, we describe the engineering of TrpB from Thermotoga maritima that improved synthesis of 4-CN-Trp from 24% to 78% yield. Remarkably, although the final enzyme maintains high thermostability ( T 50 = 93 °C), its temperature profile is shifted such that high reactivity is observed at ∼37 °C (76% yield), creating the possibility for in vivo 4-CN-Trp production. The improvements are not specific to 4-CN-Trp; a boost in activity at lower temperature is also demonstrated for other Trp analogues.

  1. Influence of the ionic liquid [C4mpy][Tf2N] on the structure of the miniprotein Trp-cage.

    Science.gov (United States)

    Baker, Joseph L; Furbish, Jeffrey; Lindberg, Gerrick E

    2015-11-01

    We examine the effect of the ionic liquid [C4mpy][Tf2N] on the structure of the miniprotein Trp-cage and contrast these results with the behavior of Trp-cage in water. We find the ionic liquid has a dramatic effect on Trp-cage, though many similarities with aqueous Trp-cage are observed. We assess Trp-cage folding by monitoring root mean square deviation from the crystallographic structure, radius of gyration, proline cis/trans isomerization state, protein secondary structure, amino acid contact formation and distance, and native and non-native contact formation. Starting from an unfolded configuration, Trp-cage folds in water at 298 K in less than 500 ns of simulation, but has very little mobility in the ionic liquid at the same temperature, which can be ascribed to the higher ionic liquid viscosity. At 365 K, the mobility of the ionic liquid is increased and initial stages of Trp-cage folding are observed, however Trp-cage does not reach the native folded state in 2 μs of simulation in the ionic liquid. Therefore, in addition to conventional molecular dynamics, we also employ scaled molecular dynamics to expedite sampling, and we demonstrate that Trp-cage in the ionic liquid does closely approach the aqueous folded state. Interestingly, while the reduced mobility of the ionic liquid is found to restrict Trp-cage motion, the ionic liquid does facilitate proline cis/trans isomerization events that are not seen in our aqueous simulations. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. TrpA1 Regulates Defecation of Food-Borne Pathogens under the Control of the Duox Pathway.

    Directory of Open Access Journals (Sweden)

    Eun Jo Du

    2016-01-01

    Full Text Available Pathogen expulsion from the gut is an important defense strategy against infection, but little is known about how interaction between the intestinal microbiome and host immunity modulates defecation. In Drosophila melanogaster, dual oxidase (Duox kills pathogenic microbes by generating the microbicidal reactive oxygen species (ROS, hypochlorous acid (HOCl in response to bacterially excreted uracil. The physiological function of enzymatically generated HOCl in the gut is, however, unknown aside from its anti-microbial activity. Drosophila TRPA1 is an evolutionarily conserved receptor for reactive chemicals like HOCl, but a role for this molecule in mediating responses to gut microbial content has not been described. Here we identify a molecular mechanism through which bacteria-produced uracil facilitates pathogen-clearing defecation. Ingestion of uracil increases defecation frequency, requiring the Duox pathway and TrpA1. The TrpA1(A transcript spliced with exon10b (TrpA1(A10b that is present in a subset of midgut enteroendocrine cells (EECs is critical for uracil-dependent defecation. TRPA1(A10b heterologously expressed in Xenopus oocytes is an excellent HOCl receptor characterized with elevated sensitivity and fast activation kinetics of macroscopic HOCl-evoked currents compared to those of the alternative TRPA1(A10a isoform. Consistent with TrpA1's role in defecation, uracil-excreting Erwinia carotovora showed higher persistence in TrpA1-deficient guts. Taken together, our results propose that the uracil/Duox pathway promotes bacteria expulsion from the gut through the HOCl-sensitive receptor, TRPA1(A10b, thereby minimizing the chances that bacteria adapt to survive host defense systems.

  3. Savannah River Site Footprint Reduction Results under the American Recovery and Reinvestment Act - 13302

    Energy Technology Data Exchange (ETDEWEB)

    Flora, Mary [Savannah River Nuclear Solutions Bldg. 730-4B, Aiken, SC 29808 (United States); Adams, Angelia [United States Department of Energy Bldg. 730-B, Aiken, SC 29808 (United States); Pope, Robert [United States Environmental Protection Agency Region IV Atlanta, GA 30303 (United States)

    2013-07-01

    The Savannah River Site (SRS) is an 802 square-kilometer United States Department of Energy (US DOE) nuclear facility located along the Savannah River near Aiken, South Carolina, managed and operated by Savannah River Nuclear Solutions. Construction of SRS began in the early 1950's to enhance the nation's nuclear weapons capability. Nuclear weapons material production began in the early 1950's, eventually utilizing five production reactors constructed to support the national defense mission. Past operations have resulted in releases of hazardous constituents and substances to soil and groundwater, resulting in 515 waste sites with contamination exceeding regulatory thresholds. More than 1,000 facilities were constructed onsite with approximately 300 of them considered radiological, nuclear or industrial in nature. In 2003, SRS entered into a Memorandum of Agreement with its regulators to accelerate the cleanup using an Area Completion strategy. The strategy was designed to focus cleanup efforts on the 14 large industrial areas of the site to realize efficiencies of scale in the characterization, assessment, and remediation activities. This strategy focuses on addressing the contaminated surface units and the vadose zone and addressing groundwater plumes subsequently. This approach streamlines characterization and remediation efforts as well as the required regulatory documentation, while enhancing the ability to make large-scale cleanup decisions. In February 2009, Congress approved the American Reinvestment and Recovery Act (ARRA) to create jobs and promote economic recovery. At SRS, ARRA funding was established in part to accelerate the completion of environmental remediation and facility deactivation and decommissioning (D and D). By late 2012, SRS achieved 85 percent footprint reduction utilizing ARRA funding by accelerating and coupling waste unit remediation with D and D of remnant facilities. Facility D and D activities were sequenced and

  4. American Recovery and Reinvestment Act (ARRA) Federal Energy Management Program Technical Assistance Project 279 IMCOM-Southeast Region: Redstone Arsenal

    Energy Technology Data Exchange (ETDEWEB)

    Hatley, Darrel D.; Goddard, James K.

    2010-09-30

    Report describing a building retuning workshop presented to staff at Redstone Arsenal. Document includes issues identified during building audits and recommendations for future activities to reduce energy use at the site.

  5. Tailoring the Glasgow University diagnostic aid for the product storage facilities at TRP

    Energy Technology Data Exchange (ETDEWEB)

    Howell, J.; Miller, E

    2001-02-01

    This report concludes the work carried out under Task D2(d)/UK D00912: Development of Anomaly Diagnosis Algorithms for a Plutonium Tank Monitoring System, which was the companion to Task D2(c)/UK D00913: Analysis and Diagnosis of Anomalies at Bulk-Handling Nuclear Materials Facilities: Benchmarking and Optimisation. Between them these tasks produced a computer software package that could diagnose anomalies in plant data pertaining to solutions of nuclear materials stored and transported around reprocessing plants. The final goal of Task UK D00912 was to demonstrate to the Agency that the software could be applied to the product storage area at the Tokai Reprocessing Plant in Japan. The University of Glasgow does not produce software to any recognisable standard, so this was not an acceptance trial, but a demonstration. It was recognised that further software development would be required before the package could be accepted as a safeguards tool. Being the final report, the report focuses on the issues that are still outstanding so those who choose to continue with this work have a clear understanding of the status of the software. It is taken for granted that the reader appreciates that the package should be able to explain relatively small anomalies (> 0.1 SQ) and has numerous features to estimate evaporation rates, pipe hold-up and so on. Here the focus is on the minor gremlins that are still to be resolved. The report first explains how the software package would be tailored so that it could be implemented at TRP. Of key importance is the fact that the plant uses scanivalves, which multiplex pressure lines from various dip-tubes onto the same pressure transducer. Although suitable for the measurement of a number of signals that are always steady, these devices are less suited to situations where tanks are frequently sparged and where the anomalies of interest inherently relate to changes in data and hence to non-steady operation. This affects the way the data

  6. Systematic and quantitative mRNA expression analysis of TRP channel genes at the single trigeminal and dorsal root ganglion level in mouse

    Directory of Open Access Journals (Sweden)

    Vandewauw Ine

    2013-02-01

    Full Text Available Abstract Background Somatosensory nerve fibres arising from cell bodies within the trigeminal ganglia (TG in the head and from a string of dorsal root ganglia (DRG located lateral to the spinal cord convey endogenous and environmental stimuli to the central nervous system. Although several members of the transient receptor potential (TRP superfamily of cation channels have been implicated in somatosensation, the expression levels of TRP channel genes in the individual sensory ganglia have never been systematically studied. Results Here, we used quantitative real-time PCR to analyse and compare mRNA expression of all TRP channels in TG and individual DRGs from 27 anatomically defined segments of the spinal cord of the mouse. At the mRNA level, 17 of the 28 TRP channel genes, TRPA1, TRPC1, TRPC3, TRPC4, TRPC5, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV4, TRPML1 and TRPP2, were detectable in every tested ganglion. Notably, four TRP channels, TRPC4, TRPM4, TRPM8 and TRPV1, showed statistically significant variation in mRNA levels between DRGs from different segments, suggesting ganglion-specific regulation of TRP channel gene expression. These ganglion-to-ganglion differences in TRP channel transcript levels may contribute to the variability in sensory responses in functional studies. Conclusions We developed, compared and refined techniques to quantitatively analyse the relative mRNA expression of all TRP channel genes at the single ganglion level. This study also provides for the first time a comparative mRNA distribution profile in TG and DRG along the entire vertebral column for the mammalian TRP channel family.

  7. Direct Binding between Pre-S1 and TRP-like Domains in TRPP Channels Mediates Gating and Functional Regulation by PIP2

    OpenAIRE

    Wang Zheng; Ruiqi Cai; Laura Hofmann; Vasyl Nesin; Qiaolin Hu; Wentong Long; Mohammad Fatehi; Xiong Liu; Shaimaa Hussein; Tim Kong; Jingru Li; Peter E. Light; Jingfeng Tang; Veit Flockerzi; Leonidas Tsiokas

    2018-01-01

    Transient receptor potential (TRP) channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5-bisphosphate (PIP2), with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3 N and C termini (N-C) that is functionally essential. The interaction was mediated by aromatic Trp81 in pre-S1 domain and cationic Lys568 in TRP-like domain. Structure-function ...

  8. Energy expenditure, body composition and insulin response to glucose in male twins discordant for the Trp64Arg polymorphism of the β3-adrenergic receptor gene

    DEFF Research Database (Denmark)

    Højlund, Kurt; Christiansen, Christian; Bjørnsbo, K.S.

    2006-01-01

    AIM: The tryptophan to arginine change in position 64 (Trp64Arg) polymorphism of the beta3-adrenergic receptor (beta3AR) gene has been associated with an increased prevalence of obesity, insulin resistance and type 2 diabetes. In this, decreased rates of energy expenditure and impaired insulin...... and environmental background, the Trp64Arg polymorphism of the beta3AR gene is associated with lower fat mass, fasting insulin levels and an appropriate insulin response to glucose. Thus, heterozygosity for the Trp64Arg variant is unlikely to increase the risk of obesity, insulin resistance or type 2 diabetes....

  9. Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2).

    Science.gov (United States)

    Grieben, Mariana; Pike, Ashley C W; Shintre, Chitra A; Venturi, Elisa; El-Ajouz, Sam; Tessitore, Annamaria; Shrestha, Leela; Mukhopadhyay, Shubhashish; Mahajan, Pravin; Chalk, Rod; Burgess-Brown, Nicola A; Sitsapesan, Rebecca; Huiskonen, Juha T; Carpenter, Elisabeth P

    2017-02-01

    Mutations in either polycystin-1 (PC1 or PKD1) or polycystin-2 (PC2, PKD2 or TRPP1) cause autosomal-dominant polycystic kidney disease (ADPKD) through unknown mechanisms. Here we present the structure of human PC2 in a closed conformation, solved by electron cryomicroscopy at 4.2-Å resolution. The structure reveals a novel polycystin-specific 'tetragonal opening for polycystins' (TOP) domain tightly bound to the top of a classic transient receptor potential (TRP) channel structure. The TOP domain is formed from two extensions to the voltage-sensor-like domain (VSLD); it covers the channel's endoplasmic reticulum lumen or extracellular surface and encloses an upper vestibule, above the pore filter, without blocking the ion-conduction pathway. The TOP-domain fold is conserved among the polycystins, including the homologous channel-like region of PC1, and is the site of a cluster of ADPKD-associated missense variants. Extensive contacts among the TOP-domain subunits, the pore and the VSLD provide ample scope for regulation through physical and chemical stimuli.

  10. A Novel Trp-rich Model Antimicrobial Peptoid with Increased Protease Stability

    International Nuclear Information System (INIS)

    Bang, Jeong Kyu; Nan, Yong Hai; Lee, Eun Kyu; Shin, Song Yub

    2010-01-01

    In order to increase protease stability of a novel Trp-rich model antimicrobial peptide, K 6 L 2 W 3 (KLWKKWKKWLKNH 2 ) and investigate the effect of L-amino acid to peptoid residue conversion on biological functions, we synthesized its antimicrobial peptoid, k 6 l 2 w 3 . Peptoid k 6 l 2 w 3 had similar bacterial selectivity compared to peptide K 6 L 2 W 3 . The bactericidal rate of k 6 l 2 w 3 was somewhat slower than that of K 6 L 2 W 3 . Peptoid k 6 l 2 w 3 exhibited very little dye leakage from bacterial outer-membrane mimicking PE/PG liposomes, as observed in K 6 L 2 W 3 , indicating that the major target site of K 6 L 2 W 3 and k 6 l 2 w 3 may be not the cell membrane but the cytoplasm of bacteria. Trypsin treatment of K 6 L 2 W 3 completely abolished antimicrobial activities against Escherichia coli and Staphylococcus aureus. In contrast, the antimicrobial activity of k 6 l 2 w 3 was completely preserved after trypsin treatment. Taken together, our results suggested that antimicrobial peptoid k 6 l 2 w 3 can potentially serves as a promising therapeutic agent for the treatment of microbial infection

  11. Mutation of I696 and W697 in the TRP box of vanilloid receptor subtype I modulates allosteric channel activation.

    Science.gov (United States)

    Gregorio-Teruel, Lucia; Valente, Pierluigi; González-Ros, José Manuel; Fernández-Ballester, Gregorio; Ferrer-Montiel, Antonio

    2014-03-01

    The transient receptor potential vanilloid receptor subtype I (TRPV1) channel acts as a polymodal sensory receptor gated by chemical and physical stimuli. Like other TRP channels, TRPV1 contains in its C terminus a short, conserved domain called the TRP box, which is necessary for channel gating. Substitution of two TRP box residues-I696 and W697-with Ala markedly affects TRPV1's response to all activating stimuli, which indicates that these two residues play a crucial role in channel gating. We systematically replaced I696 and W697 with 18 native l-amino acids (excluding cysteine) and evaluated the effect on voltage- and capsaicin-dependent gating. Mutation of I696 decreased channel activation by either voltage or capsaicin; furthermore, gating was only observed with substitution of hydrophobic amino acids. Substitution of W697 with any of the 18 amino acids abolished gating in response to depolarization alone, shifting the threshold to unreachable voltages, but not capsaicin-mediated gating. Moreover, vanilloid-activated responses of W697X mutants showed voltage-dependent gating along with a strong voltage-independent component. Analysis of the data using an allosteric model of activation indicates that mutation of I696 and W697 primarily affects the allosteric coupling constants of the ligand and voltage sensors to the channel pore. Together, our findings substantiate the notion that inter- and/or intrasubunit interactions at the level of the TRP box are critical for efficient coupling of stimulus sensing and gate opening. Perturbation of these interactions markedly reduces the efficacy and potency of the activating stimuli. Furthermore, our results identify these interactions as potential sites for pharmacological intervention.

  12. Análisis preliminar de la estructura primaria y secundaria del ARNtTrp en tortugas marinas

    Directory of Open Access Journals (Sweden)

    Harvey Infante-Rojas

    2015-06-01

    Full Text Available Actualmente existen siete especies de tortugas marinas, todas amenazadas o en riesgo inminente de extinción. Los estudios con ADN mitocondrial han permitido hacer acercamientos sobre filogenia, evolución, rutas migratorias y centros de dispersión, además para la identificación de polimorfismos y haplotipos, siendo base para planes de manejo y conservación. El presente estudio representa la primera descripción comparada de la estructura primaria y secundaria del ARNtTrp mitocondrial en tortugas marinas. Se realizó un alineamiento múltiple de 26 secuencias del gen que codifica para el ARNtTrp y se propuso la estructura secundaria utilizando el programa ARWEN. Se identificaron potenciales interacciones terciarias por homología comparada con el ARNtTrp de mamíferos. Los resultados mostraron una secuencia consenso de 76 bases con siete regiones conservadas que representan el 76 % de la molécula. Se identificaron polimorfismos que representan tres haplotipos para C. caretta, dos para C. mydas y uno para cada una de las demás especies. Las estructuras secundarias mostraron cambios nucleotídicos puntuales para cada especie y también mostraron que el tallo aceptor, el brazo TψC y el bucle anticodón son motivos conservados en el ARNtTrp de las tortugas marinas. Se encontró un enlace no canónico tipo A-A en el tallo DHU que podría considerarse característico de tortugas marinas. Además, se obtuvo una estructura secundaria consenso en donde se identificaron las siete regiones conservadas, seis posibles interacciones terciarias y el bucle DHU como región variable.

  13. Inhibition of pituitary-gonadal axis in mice by long-term administration of D-Trp-6-LHRH microcapsules.

    Science.gov (United States)

    Bokser, L; Zalatnai, A; Schally, A V

    1989-03-01

    Female mice were injected, every 30 days for 5 months, with a long-acting formulation of microcapsules liberating 2.5 micrograms D-Trp-6-LHRH/day. The control group was injected with vehicle only. At 30 days after the last injection mice were killed, ovaries, uteri and adrenals were weighed and fixed in formalin for histological studies. LH and oestradiol concentrations were measured by RIA. In the D-Trp-6-LHRH-treated group, the weights of the ovaries and uterus (P less than 0.01 and P less than 0.05, respectively), and LH and oestradiol values (P less than 0.02 and P less than 0.01, respectively) were reduced compared to controls. Histologically, the ovaries contained a large number of degenerated, atretic follicles, and corpora lutea had almost completely disappeared. These results indicate, contrary to the prevailing opinion, that mice are sensitive to inhibitory effects of LHRH agonists and that a suppression of the pituitary-gonadal axis can be obtained with long-term administration of D-Trp-6-LHRH microcapsules.

  14. High-Temperature unfolding of a trp-Cage mini-protein: a molecular dynamics simulation study

    Directory of Open Access Journals (Sweden)

    Seshasayee Aswin Sai Narain

    2005-03-01

    Full Text Available Abstract Background Trp cage is a recently-constructed fast-folding miniprotein. It consists of a short helix, a 3,10 helix and a C-terminal poly-proline that packs against a Trp in the alpha helix. It is known to fold within 4 ns. Results High-temperature unfolding molecular dynamics simulations of the Trp cage miniprotein have been carried out in explicit water using the OPLS-AA force-field incorporated in the program GROMACS. The radius of gyration (Rg and Root Mean Square Deviation (RMSD have been used as order parameters to follow the unfolding process. Distributions of Rg were used to identify ensembles. Conclusion Three ensembles could be identified. While the native-state ensemble shows an Rg distribution that is slightly skewed, the second ensemble, which is presumably the Transition State Ensemble (TSE, shows an excellent fit. The denatured ensemble shows large fluctuations, but a Gaussian curve could be fitted. This means that the unfolding process is two-state. Representative structures from each of these ensembles are presented here.

  15. Relating Trp-Glu dipeptide fluorescence to molecular conformation: the role of the discrete Chi 1 and Chi 2 angles.

    Science.gov (United States)

    Eisenberg, Azaria Solomon; Juszczak, Laura J

    2013-07-05

    Molecular dynamics (MD), coupled with fluorescence data for charged dipeptides of tryptophanyl glutamic acid (Trp-Glu), reveal a detailed picture of how specific conformation affects fluorescence. Fluorescence emission spectra and time-resolved emission measurements have been collected for all four charged species. MD simulations 20 to 30 ns in length have also been carried out for the Trp-Glu species, as simulation provides aqueous phase conformational data that can be correlated with the fluorescence data. The calculations show that each dipeptide species is characterized by a similar set of six, discrete Chi 1, Chi 2 dihedral angle pairs. The preferred Chi 1 angles--60°, 180°, and 300°--play the significant role in positioning the terminal amine relative to the indole ring. A Chi 1 angle of 60° results in the arching of the backbone over the indole ring and no interaction of the ring with the terminal amine. Chi 1 values of 180° and 300° result in an extension of the backbone away from the indole ring and a NH3 cation-π interaction with indole. This interaction is believed responsible for charge transfer quenching. Two fluorescence lifetimes and their corresponding amplitudes correlate with the Chi 1 angle probability distribution for all four charged Trp-Glu dipeptides. Fluorescence emission band maxima are also consistent with the proposed pattern of terminal amine cation quenching of fluorescence. Copyright © 2013 Wiley Periodicals, Inc.

  16. Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: histidine substitution.

    Science.gov (United States)

    Cheung, Adrian Wai-Hing; Danho, Waleed; Swistok, Joseph; Qi, Lida; Kurylko, Grazyna; Rowan, Karen; Yeon, Mitch; Franco, Lucia; Chu, Xin-Jie; Chen, Li; Yagaloff, Keith

    2003-01-06

    Systematic substitution of His(6) residue using non-selective hMC4R pentapeptide agonist (Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2)) as the template led to the identification of Bu-Atc(6)(2-aminotetraline-2-carboxylic acid)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) which showed moderate selectivity towards hMC4R over hMC1R. Further SAR studies resulted in the discovery of Penta-5-BrAtc(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) and Penta-5-Me(2)NAtc(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) which are potent hMC4R agonists and are inactive in hMC1R, hMC3R and hMC5R agonist assays.

  17. 78 FR 49264 - Nationwide Categorical Waivers Under the American Recovery and Reinvestment Act of 2009 (Recovery...

    Science.gov (United States)

    2013-08-13

    ... specified infra) to be utilized in the San Antonio River Walk Project, being performed under a subgrant from... quantities and of a satisfactory quality. The above items, utilized in the San Antonio River Walk Project... Standards and Technology (NIST) Manufacturing Extension Partnership (MEP), in order to scour the domestic...

  18. The tumor suppressor gene Trp53 protects the mouse lens against posterior subcapsular cataracts and the BMP receptor Acvr1 acts as a tumor suppressor in the lens

    Directory of Open Access Journals (Sweden)

    Luke A. Wiley

    2011-07-01

    We previously found that lenses lacking the Acvr1 gene, which encodes a bone morphogenetic protein (BMP receptor, had abnormal proliferation and cell death in epithelial and cortical fiber cells. We tested whether the tumor suppressor protein p53 (encoded by Trp53 affected this phenotype. Acvr1 conditional knockout (Acvr1CKO mouse fiber cells had increased numbers of nuclei that stained for p53 phosphorylated on serine 15, an indicator of p53 stabilization and activation. Deletion of Trp53 rescued the Acvr1CKO cell death phenotype in embryos and reduced Acvr1-dependent apoptosis in postnatal lenses. However, deletion of Trp53 alone increased the number of fiber cells that failed to withdraw from the cell cycle. Trp53CKO and Acvr1;Trp53DCKO (double conditional knockout, but not Acvr1CKO, lenses developed abnormal collections of cells at the posterior of the lens that resembled posterior subcapsular cataracts. Cells from human posterior subcapsular cataracts had morphological and molecular characteristics similar to the cells at the posterior of mouse lenses lacking Trp53. In Trp53CKO lenses, cells in the posterior plaques did not proliferate but, in Acvr1;Trp53DCKO lenses, many cells in the posterior plaques continued to proliferate, eventually forming vascularized tumor-like masses at the posterior of the lens. We conclude that p53 protects the lens against posterior subcapsular cataract formation by suppressing the proliferation of fiber cells and promoting the death of any fiber cells that enter the cell cycle. Acvr1 acts as a tumor suppressor in the lens. Enhancing p53 function in the lens could contribute to the prevention of steroid- and radiation-induced posterior subcapsular cataracts.

  19. ADRB3 Gene Trp64Arg Polymorphism and Essential Hypertension: A Meta-Analysis Including 9,555 Subjects.

    Science.gov (United States)

    Li, Yan-Yan; Lu, Xin-Zheng; Wang, Hui; Zhou, Yan-Hong; Yang, Xin-Xing; Geng, Hong-Yu; Gong, Ge; Kim, Hyun Jun

    2018-01-01

    Background: Presence of the β 3-Adrenergic receptor (ADRB3) gene Trp64Arg (T64A) polymorphism may be associated with an increased susceptibility for essential hypertension (EH). A clear consensus, however, has yet to be reached. Objective and methods: To further elucidate the relationship between the ADRB3 gene Trp64Arg polymorphism and EH, a meta-analysis of 9,555 subjects aggregated from 16 individual studies was performed. The combined odds ratios (ORs) and their corresponding 95% confidence intervals (CI) were evaluated using either a random or fixed effect model. Results: We found a marginally significant association between ADRB3 gene Trp64Arg polymorphism and EH in the whole population under the additive genetic model (OR: 1.200, 95% CI: 1.00-1.43, P = 0.049). Association within the Chinese subgroup, however, was significant under allelic (OR: 1.150, 95% CI: 1.002-1.320, P = 0.046), dominant (OR: 1.213, 95% CI: 1.005-1.464, P = 0.044), heterozygous (OR: 1.430, 95% CI:1.040-1.970, P = 0.03), and additive genetic models (OR: 1.280, 95% CI: 1.030-1.580, P = 0.02). A significant association was also found in the Caucasian subgroup under allelic (OR: 1.850, 95% CI: 1. 260-2.720, P = 0.002), dominant (OR: 2.004, 95% CI: 1.316-3.052, P = 0.001), heterozygous (OR: 2.220, 95% CI: 1.450-3.400, P = 0.0002), and additive genetic models (OR: 2.000, 95% CI: 1. 330-3.010, P = 0.0009). Conclusions: The presence of the ADRB3 gene Trp64Arg polymorphism is positively associated with EH, especially in the Chinese and Caucasian population. The Arg allele carriers of ADRB3 gene Trp64Arg polymorphism may be at an increased risk for developing EH.

  20. Meta-analyses of KIF6 Trp719Arg in coronary heart disease and statin therapeutic effect.

    Directory of Open Access Journals (Sweden)

    Ping Peng

    Full Text Available The goal of our study is to assess the contribution of KIF6 Trp719Arg to both the risk of CHD and the efficacy of statin therapy in CHD patients.Meta-analysis of 8 prospective studies among 77,400 Caucasians provides evidence that 719Arg increases the risk of CHD (P<0.001, HR = 1.27, 95% CI = 1.15-1.41. However, another meta-analysis of 7 case-control studies among 65,200 individuals fails to find a significant relationship between Trp719Arg and the risk of CHD (P = 0.642, OR = 1.02, 95% CI = 0.95-1.08. This suggests that the contribution of Trp719Arg to CHD varies in different ethnic groups. Additional meta-analysis also shows that statin therapy only benefit the vascular patients carry 719Arg allele (P<0.001, relative ratio (RR = 0.60, 95% CI = 0.54-0.67. To examine the role of this genetic variant in CHD risk in Han Chinese, we have conducted a case-control study with 289 CHD cases, 193 non-CHD controls, and 329 unrelated healthy volunteers as healthy controls. On post hoc analysis, significant allele frequency difference of 719Arg is observed between female CHD cases and female total controls under the dominant model (P = 0.04, χ(2 = 4.228, df = 1, odd ratio (OR = 1.979, 95% confidence interval (CI = 1.023-3.828. Similar trends are observed for post hoc analysis between female CHD cases and female healthy controls (dominant model: P = 0.04, χ(2 = 4.231, df = 1, OR = 2.015, 95% CI = 1.024-3.964. Non-genetic CHD risk factors are not controlled in these analyses.Our meta-analysis demonstrates the role of Trp719Arg of KIF6 gene in the risk of CHD in Caucasians. The meta-analysis also suggests the role of this variant in statin therapeutic response in vascular diseases. Our case-control study suggests that Trp719Arg of KIF6 gene is associated with CHD in female Han Chinese through a post hoc analysis.

  1. The Use of the Hanford Onsite Packaging and Transportation Safety Program to Meet Cleanup Milestones Under the Hanford Site Cleanup 2015 Vision and the American Recovery and Reinvestment Act of 2009 - 12403

    Energy Technology Data Exchange (ETDEWEB)

    Lavender, John C. [CH2M HILL Plateau Remediation Company, Richland, WA 99354 (United States); Edwards, W. Scott [Areva Federal Services, Richland, WA 99354 (United States); Macbeth, Paul J.; Self, Richard J. [U.S. Department of Energy Richland Operations Office, Richland, WA 99352 (United States); West, Lori D. [Materials and Energy Corporation, Richland, WA 99354 (United States)

    2012-07-01

    The Hanford Site presents unique challenges in meeting the U.S. Department of Energy Richland Operations Office (DOE-RL) 2015 Cleanup Vision. CH2M Hill Plateau Remediation Company (CHPRC), its subcontractors, and DOE-RL were challenged to retrieve, transport and remediate a wide range of waste materials. Through a collaborative effort by all Hanford Onsite Central Plateau Cleanup Team Members, disposition pathways for diverse and seemingly impossible to ship wastes were developed under a DOE Order 460.1C-compliant Hanford Onsite Transportation Safety Program. The team determined an effective method for transporting oversized compliant waste payloads to processing and disposition facilities. The use of the onsite TSD packaging authorizations proved to be vital to safely transporting these materials for processing and eventual final disposition. The American Recovery and Reinvestment Act of 2009 (ARRA) provided additional resources to expedite planning and execution of these important cleanup milestones. Through the innovative and creative use of the TSD, the Hanford Onsite Central Plateau Cleanup Team Members have developed and are executing an integrated project plan that enables the safe and compliant transport of a wide variety of difficult-to-transport waste items, accelerating previous cleanup schedules to meet cleanup milestones. (authors)

  2. The core domain as the force sensor of the yeast mechanosensitive TRP channel.

    Science.gov (United States)

    Su, Zhenwei; Anishkin, Andriy; Kung, Ching; Saimi, Yoshiro

    2011-12-01

    Stretch-activated conductances are commonly encountered in careful electric recordings. Those of known proteins (TRP, MscL, MscS, K(2p), Kv, etc.) all share a core, which houses the ion pathway and the gate, but no recognizable force-sensing domain. Like animal TRPs, the yeast TRPY1 is polymodal, activated by stretch force, Ca(2+), etc. To test whether its S5-S6 core senses the stretch force, we tried to uncouple it from the peripheral domains by strategic peptide insertions to block the covalent core-periphery interactions. Insertion of long unstructured peptides should distort, if not disrupt, protein structures that transmit force. Such insertions between S6 and the C-terminal tail largely removed Ca(2+) activation, showing their effectiveness. However, such insertions as well as those between S5 and the N-terminal region, which includes S1-S4, did not significantly alter mechanosensitivity. Even insertions at both locations flanking the S5-S6 core did not much alter mechanosensitivity. Tryptophan scanning mutations in S5 were also constructed to perturb possible noncovalent core-periphery contacts. The testable tryptophan mutations also have little or no effects on mechanosensitivity. Boltzmann fits of the wild-type force-response curves agree with a structural homology model for a stretch-induced core expansion of ~2 nm(2) upon opening. We hypothesize that membrane tension pulls on S5-S6, expanding the core and opening the TRPY1 gate. The core being the major force sensor offers the simplest, though not the only, explanation of why so many channels of disparate designs are mechanically sensitive. Compared with the bacterial MscL, TRPY1 is much less sensitive to force, befitting a polymodal channel that relies on multiple stimuli.

  3. Revisiting the Role of TRP, Orai, and ASIC Channels in the Pulmonary Arterial Response to Hypoxia

    Directory of Open Access Journals (Sweden)

    Roberto V. Reyes

    2018-05-01

    Full Text Available The pulmonary arteries are exquisitely responsive to oxygen changes. They rapidly and proportionally contract as arterial PO2 decrease, and they relax as arterial PO2 is re-established. The hypoxic pulmonary vasoconstriction (HPV is intrinsic since it does not require neural or endocrine factors, as evidenced in isolated vessels. On the other hand, pulmonary arteries also respond to sustained hypoxia with structural and functional remodeling, involving growth of smooth muscle medial layer and later recruitment of adventitial fibroblasts, secreted mitogens from endothelium and changes in the response to vasoconstrictor and vasodilator stimuli. Hypoxic pulmonary arterial vasoconstriction and remodeling are relevant biological responses both under physiological and pathological conditions, to explain matching between ventilation and perfusion, fetal to neonatal transition of pulmonary circulation and pulmonary artery over-constriction and thickening in pulmonary hypertension. Store operated channels (SOC and receptor operated channels (ROC are plasma membrane cationic channels that mediate calcium influx in response to depletion of internal calcium stores or receptor activation, respectively. They are involved in both HPV and pathological remodeling since their pharmacological blockade or genetic suppression of several of the Stim, Orai, TRP, or ASIC proteins in SOC or ROC complexes attenuate the calcium increase, the tension development, the pulmonary artery smooth muscle proliferation, and pulmonary arterial hypertension. In this Mini Review, we discussed the evidence obtained in in vivo animal models, at the level of isolated organ or cells of pulmonary arteries, and we identified and discussed the questions for future research needed to validate these signaling complexes as targets against pulmonary hypertension.

  4. Platelet dysfunction associated with the novel Trp29Cys thromboxane A₂ receptor variant.

    Science.gov (United States)

    Mumford, A D; Nisar, S; Darnige, L; Jones, M L; Bachelot-Loza, C; Gandrille, S; Zinzindohoue, F; Fischer, A-M; Mundell, S J; Gaussem, P

    2013-03-01

    Genetic variations that affect the structure of the thromboxane A2 receptor (TP receptor) provide insights into the function of this key platelet and vascular receptor, but are very rare in unselected populations. To determine the functional consequences of the TP receptor Trp29Cys (W29C) substitution. We performed a detailed phenotypic analysis of an index case (P1) with reduced platelet aggregation and secretion responses to TP receptor pathway activators, and a heterozygous TP receptor W29C substitution. An analysis of the variant W29C TP receptor expressed in heterologous cells was performed. Total TP receptor expression in platelets from P1 was similar to that of controls, but there was reduced maximum binding and reduced affinity of binding to the TP receptor antagonist [(3) H]SQ29548. HEK293 cells transfected with W29C TP receptor cDNA showed similar total TP receptor expression to wild-type (WT) controls. However, the TP receptor agonist U46619 was less potent at inducing rises in cytosolic free Ca(2+) in HEK293 cells expressing the W29C TP receptor than in WT controls, indicating reduced receptor function. Immunofluorescence microscopy and cell surface ELISA showed intracellular retention and reduced cell surface expression of the W29C TP receptor in HEK293 cells. Consistent with the platelet phenotype, both maximum binding and the affinity of binding of [(3) H]SQ29548 to the W29C TP receptor were reduced compared to WT controls. These findings extend the phenotypic description of the very rare disorder TP receptor deficiency, and show that the W29C substitution reduces TP receptor function by reducing surface receptor expression and by disrupting ligand binding. © 2012 International Society on Thrombosis and Haemostasis.

  5. Microsecond simulations of the folding/unfolding thermodynamics of the Trp-cage mini protein

    Science.gov (United States)

    Day, Ryan; Paschek, Dietmar; Garcia, Angel E.

    2012-01-01

    We study the unbiased folding/unfolding thermodynamics of the Trp-cage miniprotein using detailed molecular dynamics simulations of an all-atom model of the protein in explicit solvent, using the Amberff99SB force field. Replica-exchange molecular dynamics (REMD) simulations are used to sample the protein ensembles over a broad range of temperatures covering the folded and unfolded states, and at two densities. The obtained ensembles are shown to reach equilibrium in the 1 μs per replica timescale. The total simulation time employed in the calculations exceeds 100 μs. Ensemble averages of the fraction folded, pressure, and energy differences between the folded and unfolded states as a function of temperature are used to model the free energy of the folding transition, ΔG(P,T), over the whole region of temperature and pressures sampled in the simulations. The ΔG(P,T) diagram describes an ellipse over the range of temperatures and pressures sampled, predicting that the system can undergo pressure induced unfolding and cold denaturation at low temperatures and high pressures, and unfolding at low pressures and high temperatures. The calculated free energy function exhibits remarkably good agreement with the experimental folding transition temperature (Tf = 321 K), free energy and specific heat changes. However, changes in enthalpy and entropy are significantly different than the experimental values. We speculate that these differences may be due to the simplicity of the semi-empirical force field used in the simulations and that more elaborate force fields may be required to describe appropriately the thermodynamics of proteins. PMID:20408169

  6. Modulation of innate and learned sexual behaviors by the TRP channel Painless expressed in the fruit fly brain: behavioral genetic analysis and its implications

    Directory of Open Access Journals (Sweden)

    Shoma eSato

    2014-12-01

    Full Text Available Transient receptor potential (TRP channels have attracted considerable attention because of their vital roles in primary sensory neurons, mediating responses to a wide variety of external environmental stimuli. However, much less is known about how TRP channels in the brain respond to intrinsic signals and are involved in neurophysiological processes that control complex behaviors. Painless (Pain is the Drosophila TRP channel that was initially identified as a molecular sensor responsible for detecting noxious thermal and mechanical stimuli. Here, we review recent behavioral genetic studies demonstrating that Pain expressed in the brain plays a critical role in both innate and learned aspects of sexual behaviors. Several members of the TRP channel superfamily play evolutionarily conserved roles in sensory neurons as well as in other peripheral tissues. It is thus expected that brain TRP channels in vertebrates and invertebrates would have some common physiological functions. Studies of Pain in the Drosophila brain using a unique combination of genetics and physiological techniques should provide valuable insights into the fundamental principles concerning TRP channels expressed in the vertebrate and invertebrate brains.

  7. 75 FR 61163 - Buy American Exceptions Under the American Recovery and Reinvestment Act of 2009

    Science.gov (United States)

    2010-10-04

    ... the Lincoln Way and Jackson Gardens projects, and for the purchase and installation of solar panels... goods (solar panels and linoleum) are not produced in the U.S. in sufficient and reasonably available...

  8. TRP and ASIC channels mediate the antinociceptive effect of citronellyl acetate.

    Science.gov (United States)

    Rios, Emiliano Ricardo Vasconcelos; Rocha, Nayrton Flávio Moura; Carvalho, Alyne Mara Rodrigues; Vasconcelos, Leonardo Freire; Dias, Marília Leite; de Sousa, Damião Pergentino; de Sousa, Francisca Cléa Florenço; Fonteles, Marta Maria de França

    2013-05-25

    Citronellyl acetate (CAT), a monoterpene product of the secondary metabolism of plants, has been shown in the literature to possess several different biological activities. However, no antinociceptive abilities have yet been discussed. Here, we used acute pain animal models to describe the antinociceptive action of CAT. The acetic acid-induced writhing test and the paw-licking test, in which paw licking was induced by glutamate and formalin, were performed to evaluate the antinociceptive action of CAT and to determine the involvement of PKC, PKA, TRPV1, TRPA1, TRPM8 and ASIC in its antinociceptive mechanism. To do so, we induced paw-linking using agonists. CAT was administered intragastrically (25, 50, 75, 100 and 200 mg/kg), and the two higher doses caused antinociceptive effects in the acetic acid model; the highest dose reduced pain for 4h after it was administered (200 mg/kg). In the formalin test, two doses of CAT promoted antinociception in both the early and later phases of the test. The glutamate test showed that its receptors are involved in the antinociceptive mechanism of CAT. Pretreatment with CAT did not alter locomotor activity or motor coordination. In an investigation into the participation of TRP channels and ASICs in CAT's antinociceptive mechanism, we used capsaicin (2.2 μg/paw), cinnamaldehyde (10 mmol/paw), menthol (1.2 mmol/paw) and acidified saline (2% acetic acid, pH 1.98). The results showed that TRPV1, TRPM8 and ASIC, but not TRPA1, are involved in the antinociceptive mechanism. Finally, the involvement of PKC and PKA was also studied, and we showed that both play a role in the antinociceptive mechanism of CAT. The results of this work contribute information regarding the antinociceptive properties of CAT on acute pain and show that, at least in part, TRPV1, TRPM8, ASIC, glutamate receptors, PKC and PKA participate in CAT's antinociceptive mechanism. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Structural and population-based evaluations of TBC1D1 p.Arg125Trp.

    Directory of Open Access Journals (Sweden)

    Tom G Richardson

    Full Text Available Obesity is now a leading cause of preventable death in the industrialised world. Understanding its genetic influences can enhance insight into molecular pathogenesis and potential therapeutic targets. A non-synonymous polymorphism (rs35859249, p.Arg125Trp in the N-terminal TBC1D1 phosphotyrosine-binding (PTB domain has shown a replicated association with familial obesity in women. We investigated these findings in the Avon Longitudinal Study of Parents and Children (ALSPAC, a large European birth cohort of mothers and offspring, and by generating a predicted model of the structure of this domain. Structural prediction involved the use of three separate algorithms; Robetta, HHpred/MODELLER and I-TASSER. We used the transmission disequilibrium test (TDT to investigate familial association in the ALSPAC study cohort (N = 2,292 mother-offspring pairs. Linear regression models were used to examine the association of genotype with mean measurements of adiposity (Body Mass Index (BMI, waist circumference and Dual-energy X-ray absorptiometry (DXA assessed fat mass, and logistic regression was used to examine the association with odds of obesity. Modelling showed that the R125W mutation occurs in a location of the TBC1D1 PTB domain that is predicted to have a function in a putative protein:protein interaction. We did not detect an association between R125W and BMI (mean per allele difference 0.27 kg/m(2 (95% Confidence Interval: 0.00, 0.53 P = 0.05 or obesity (odds ratio 1.01 (95% Confidence Interval: 0.77, 1.31, P = 0.96 in offspring after adjusting for multiple comparisons. Furthermore, there was no evidence to suggest that there was familial association between R125W and obesity (χ(2 = 0.06, P = 0.80. Our analysis suggests that R125W in TBC1D1 plays a role in the binding of an effector protein, but we find no evidence that the R125W variant is related to mean BMI or odds of obesity in a general population sample.

  10. Trp64Arg polymorphism of the ADRB3 gene associated with maximal fat oxidation and LDL-C levels in non-obese adolescents.

    Science.gov (United States)

    Jesus, Íncare Correa de; Alle, Lupe Furtado; Munhoz, Eva Cantalejo; Silva, Larissa Rosa da; Lopes, Wendell Arthur; Tureck, Luciane Viater; Purim, Katia Sheylla Malta; Titski, Ana Claudia Kapp; Leite, Neiva

    2017-09-21

    To analyze the association between the Trp64Arg polymorphism of the ADRB3 gene, maximal fat oxidation rates and the lipid profile levels in non-obese adolescents. 72 schoolchildren, of both genders, aged between 11 and 17 years, participated in the study. The anthropometric and body composition variables, in addition to total cholesterol, HDL-c, LDL-c, triglycerides, insulin, and basal glycemia, were evaluated. The sample was divided into two groups according to the presence or absence of the polymorphism: non-carriers of the Arg64 allele, i.e., homozygous (Trp64Trp: n=54), and carriers of the Arg64 allele (Trp64Arg+Arg64Arg: n=18), in which the frequency of the Arg64 allele was 15.2%. The maximal oxygen uptake and peak of oxygen uptake during exercise were obtained through the symptom-limited, submaximal treadmill test. Maximal fat oxidation was determined according to the ventilatory ratio proposed in Lusk's table. Adolescents carrying the less frequent allele (Trp64Arg and Arg64Arg) had higher LDL-c levels (p=0.031) and lower maximal fat oxidation rates (p=0.038) when compared with non-carriers (Trp64Trp). Although the physiological processes related to lipolysis and lipid metabolism are complex, the presence of the Arg 64 allele was associated with lower rates of FATMAX during aerobic exercise, as well as with higher levels of LDL-c in adolescents. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  11. 77 FR 49006 - Buy American Exceptions Under the American Recovery and Reinvestment Act of 2009

    Science.gov (United States)

    2012-08-15

    ... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5374-N-42] Buy American Exceptions... power cords for the Village at River's Edge project, and to the Hammond Housing Authority for the... Public and Indian Housing, Department of Housing and Urban Development, 451 7th Street SW., Room 4112...

  12. 76 FR 30966 - Buy American Exception Under the American Recovery and Reinvestment Act of 2009

    Science.gov (United States)

    2011-05-27

    ... the Buy American waiver requested by the Deschutes River Conservancy (DRC) to purchase foreign... project contract by more than 25 percent. The waiver process is initiated by a requesting organization... its Buy American decision is required pursuant to the Buy American Act, 2 CFR 176.80(b)(2). Upon...

  13. 76 FR 54486 - Buy American Exception Under the American Recovery and Reinvestment Act of 2009

    Science.gov (United States)

    2011-09-01

    ... decision to approve the Buy American waiver requested by the SDBOC to purchase foreign ductile iron flanges... the Buy American waiver requested by the Sunnyside Division Board of Control (SDBOC) to purchase... will increase the cost of the overall project contract by more than 25 percent. The waiver process is...

  14. 75 FR 35447 - Buy American Exception Under the American Recovery and Reinvestment Act of 2009; Nationwide...

    Science.gov (United States)

    2010-06-22

    ... domestic manufacturers and possess extensive knowledge of their specific capabilities. The EERE--MEP... capabilities. De Minimis Public Interest Waiver Pursuant to the above-referenced delegation the Assistant... the physical structure of the project, such as nuts, bolts, wires, cables, switches, etc. For many of...

  15. Investigation of KIF6 Trp719Arg in a case-control study of myocardial infarction: a Costa Rican population.

    Directory of Open Access Journals (Sweden)

    Lance A Bare

    2010-09-01

    Full Text Available The 719Arg allele of KIF6 (rs20455 was associated with coronary events in Caucasian participants of five prospective studies. We investigated whether this KIF6 variant was associated with non-fatal myocardial infarction (MI in a case-control study of an admixed population from the Central Valley of Costa Rica. Genotypes of the KIF6 variant were determined for 4,134 men and women. Cases (1,987 had survived a first MI; controls (2,147 had no history of MI and were matched to cases by age, sex, and area of residence. We tested the association between the KIF6 719Arg allele and non-fatal MI by conditional logistic regression and adjusted for admixture of founder populations.Compared with the reference Trp/Trp homozygotes, KIF6 719Arg carriers were not at significantly higher risk for non-fatal MI in this study after adjustment for traditional risk factors or admixture (OR= 1.12; 95%CI, 0.98-1.28. Heterozygotes of the KIF6 Trp719Arg variant were at increased risk of non-fatal MI: the adjusted odds ratio was 1.16 (95% confidence interval, 1.01-1.34, but this association would not be significant after a multiple testing correction.We found that carriers of the KIF6 719Arg allele were not at increased risk of non-fatal MI in a case-control study of Costa Ricans living in the Central Valley of Costa Rica.

  16. A second tyrosinase-related protein, TRP-2, maps to and is mutated at the mouse slaty locus.

    OpenAIRE

    Jackson, I J; Chambers, D M; Tsukamoto, K; Copeland, N G; Gilbert, D J; Jenkins, N A; Hearing, V

    1992-01-01

    We have cloned and sequenced mouse cDNAs corresponding to a third member of a family of melanocyte-specific mRNAs, which encode tyrosinase and related proteins. This new member, tyrosinase-related protein-2 (TRP-2), has approximately 40% amino acid identity with the two other proteins in the family and has the same structural features including two copper binding sites, two cysteine-rich regions, a signal peptide and a transmembrane domain. We now show that one of the cysteine-rich regions in...

  17. Can the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) be used to accurately report clinic total reproductive potential (TRP)?

    Science.gov (United States)

    Stern, Judy E; Hickman, Timothy N; Kinzer, Donna; Penzias, Alan S; Ball, G David; Gibbons, William E

    2012-04-01

    To assess whether total reproductive potential (TRP), the chance of a live birth from each fresh cycle (fresh cycle plus frozen transfers), could be calculated from the national Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database and whether information not available in SART CORS resulted in significant changes to the TRP calculation. Retrospective study using SART CORS and clinic data. Three assisted reproductive technology clinics. Women undergoing ART. None. Two- and three-year TRPs for 2005 and 2006 were calculated according to patient age at cycle start by linking fresh to frozen cycles up to first live birth. Clinic records were used to adjust for (remove) frozen cycles that used more than one fresh cycle as a source of embryos and for any embryos donated to other patients or research or shipped to another facility before a live birth. TRP was higher than fresh per-cycle rates for most ages at all clinics, although accuracy was compromised when there were fewer than 20 cycles per category. Two- and 3-year TRPs differed in only 2 of 24 calculations. Adjusted TRPs differed less than three percentage points from unadjusted TRPs when volume was sufficient. Clinic TRP can be calculated from SART CORS. Data suggest that calculations of clinic TRP from the national dataset would be meaningful. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Knockout and transgenic mice of Trp53: what have we learned about p53 in breast cancer?

    International Nuclear Information System (INIS)

    Blackburn, Anneke C; Jerry, D Joseph

    2002-01-01

    The human p53 tumor suppressor gene TP53 is mutated at a high frequency in sporadic breast cancer, and Li-Fraumeni syndrome patients who carry germline mutations in one TP53 allele have a high incidence of breast cancer. In the 10 years since the first knockout of the mouse p53 tumor suppressor gene (designated Trp53) was published, much has been learned about the contribution of p53 to biology and tumor suppression in the breast through the use of p53 transgenic and knockout mice. The original mice deficient in p53 showed no mammary gland phenotype. However, studies using BALB/c-Trp53-deficient mice have demonstrated a delayed involution phenotype and a mammary tumor phenotype. Together with other studies of mutant p53 transgenes and p53 bitransgenics, a greater understanding has been gained of the role of p53 in involution, of the regulation of p53 activity by hormones, of the effect of mouse strain and modifier genes on tumor phenotype, and of the cooperation between p53 and other oncogenic pathways, chemical carcinogens and hormonal stimulation in mammary tumorigenesis. Both p53 transgenic and knockout mice are important in vivo tools for understanding breast cancer, and are yet to be exploited for developing therapeutic strategies in breast cancer

  19. Transient Receptor Potential channels: What's happening? Reflections in the wake of the 2009 TRP Meeting, Karolinska Institutet, Stockholm.

    Science.gov (United States)

    Goswami, Chandan; Islam, Md Shahidul

    2010-01-01

    More than 150 participants from 25 countries gathered in Stockholm during 25(th) to 27(th) Sept 2009 to attend the meeting "TRP channels: from sensory signaling to human disease" and enjoyed an international, intensive and vibrant meeting. This meeting shed lights on the recent advances made in this field of research in different sectors of biology, and identified directions for future research and the areas where TRP channels could be used as potential targets for prevention and treatment of human diseases. The participants of this meeting shared their recent largely unpublished data, state-of-the-art techniques and their critical views which would push research in this field forward in the new decade. Another major outcome of this meeting was the realization that extensive work remains to be done to develop the necessary tools and enhance the quality of research in this area so that the prevailing controversies can be resolved. In this report we summarize the latest scientific excitements, some critical issues, as well as some future directions for research that were addressed and discussed in this meeting.

  20. Extracts and compounds active on TRP ion channels from Waldheimia glabra, a ritual medicinal plant from Himalaya.

    Science.gov (United States)

    Giorgi, Annamaria; Bassoli, Angela; Borgonovo, Gigliola; Panseri, Sara; Manzo, Alessandra; Pentimalli, Daniela; Schiano Moriello, Aniello; De Petrocellis, Luciano

    2017-08-15

    Waldheimia glabra (Decne.) Regel is a wild plant from the Himalayan Mountains, commonly known as Smooth Ground Daisy. This plant is traditionally used by local populations in religious rituals (incense) or in traditional herbal medicine to treat skin diseases, headache, joint pain and fever. In literature few data are available on the investigation of this aromatic plant. The present work aims at deepening knowledge about the chemical composition of W. glabra extracts and incense, as well as its activity on TRP ion channels. Extracts and incense of W. glabra were analyzed by using HS-SPME GC/MS, GC/MS and NMR analysis. Tests on the activity of W. glabra extracts and isolated compounds (+)-ludartin 1 and B-ring-homo-tonghaosu 2 on TRP channels were also performed. Some extracts and pure compounds from W. glabra showed an interesting activity in terms of efficacy and potency on rat TRPA1, an ion channel involved in several sensory mechanisms, including pungency, environmental irritation and pain perception. Activity is discussed and compared with that of other known TRPA1 natural agonists with different chemical structures. All compounds showed only a negligible inhibition activity on rat TRPM8 ion channel. Our findings demonstrate that W. glabra is involved in the receptor activation mechanism and therefore represents a new natural product potentially useful in pharmaceutical and agrifood research. Copyright © 2017 Elsevier GmbH. All rights reserved.

  1. Synthesis and Pharmacology of α/β(3)-Peptides Based on the Melanocortin Agonist Ac-His-dPhe-Arg-Trp-NH2 Sequence.

    Science.gov (United States)

    Singh, Anamika; Tala, Srinivasa R; Flores, Viktor; Freeman, Katie; Haskell-Luevano, Carrie

    2015-05-14

    The melanocortin-3 and -4 receptors are expressed in the brain and play key roles in regulating feeding behavior, metabolism, and energy homeostasis. In the present study, incorporation of β(3)-amino acids into a melanocortin tetrapeptide template was investigated. Four linear α/β(3)-hybrid tetrapeptides were designed with the modifications at the Phe, Arg, and Trp residues in the agonist sequence Ac-His-dPhe-Arg-Trp-NH2. The most potent mouse melanocortin-4 receptor (mMC4R) agonist, Ac-His-dPhe-Arg-β(3)hTrp-NH2 (8) showed 35-fold selectivity versus the mMC3R. The study presented here has identified a new template with heterogeneous backbone for designing potent and selective melanocortin receptor ligands.

  2. Synthesis and Pharmacology of α/β3-Peptides Based on the Melanocortin Agonist Ac-His-dPhe-Arg-Trp-NH2 Sequence

    Science.gov (United States)

    2015-01-01

    The melanocortin-3 and -4 receptors are expressed in the brain and play key roles in regulating feeding behavior, metabolism, and energy homeostasis. In the present study, incorporation of β3-amino acids into a melanocortin tetrapeptide template was investigated. Four linear α/β3-hybrid tetrapeptides were designed with the modifications at the Phe, Arg, and Trp residues in the agonist sequence Ac-His-dPhe-Arg-Trp-NH2. The most potent mouse melanocortin-4 receptor (mMC4R) agonist, Ac-His-dPhe-Arg-β3hTrp-NH2 (8) showed 35-fold selectivity versus the mMC3R. The study presented here has identified a new template with heterogeneous backbone for designing potent and selective melanocortin receptor ligands. PMID:26005535

  3. A lower dose threshold for the in vivo protective adaptive response to radiation. Tumorigenesis in chronically exposed normal and Trp53 heterozygous C57BL/6 mice

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.; Burchart, P.; Wyatt, H.

    2008-01-01

    Low doses of ionizing radiation to cells and animals may induce adaptive responses that reduce the risk of cancer. However, there are upper dose thresholds above which these protective adaptive responses do not occur. We have now tested the hypothesis that there are similar lower dose thresholds that must be exceeded in order to induce protective effects in vivo. We examined the effects of low dose/low dose rate fractionated exposures on cancer formation in Trp53 normal or cancer-prone Trp53 heterozygous female C57BL/6 mice. Beginning at 6 weeks of age, mice were exposed 5 days/week to single daily doses (0.33 mGy, 0.7 mGy/h) totaling 48, 97 or 146 mGy over 30, 60 or 90 weeks. The exposures for shorter times (up to 60 weeks) appeared to be below the level necessary to induce overall protective adaptive responses in Trp53 normal mice, and detrimental effects (shortened lifespan, increased frequency) evident for only specific tumor types (B- and T-cell lymphomas), were produced. Only when the exposures were continued for 90 weeks did the dose become sufficient to induce protective adaptive responses, balancing the detrimental effects for these specific cancers, and reducing the risk level back to that of the unexposed animals. Detrimental effects were not seen for other tumor types, and a protective effect was seen for sarcomas after 60 weeks of exposure, which was then lost when the exposure continued for 90 weeks. As previously shown for the upper dose threshold for protection by low doses, the lower dose boundary between protection and harm was influenced by Trp53 functionality. Neither protection nor harm was observed in exposed Trp53 heterozygous mice, indicating that reduced Trp53 function raises the lower dose/dose rate threshold for both detrimental and protective tumorigenic effects. (author)

  4. Alternative SAIL-Trp for robust aromatic signal assignment and determination of the {chi}{sub 2} conformation by intra-residue NOEs

    Energy Technology Data Exchange (ETDEWEB)

    Miyanoiri, Yohei; Takeda, Mitsuhiro [Nagoya University, Graduate School of Science, Structural Biology Research Center (Japan); Jee, JunGoo; Ono, Akira M.; Okuma, Kosuke; Terauchi, Tsutomu [Tokyo Metropolitan University, Center for Priority Areas (Japan); Kainosho, Masatsune, E-mail: kainosho@nagoya-u.jp [Nagoya University, Graduate School of Science, Structural Biology Research Center (Japan)

    2011-12-15

    Tryptophan (Trp) residues are frequently found in the hydrophobic cores of proteins, and therefore, their side-chain conformations, especially the precise locations of the bulky indole rings, are critical for determining structures by NMR. However, when analyzing [U-{sup 13}C,{sup 15}N]-proteins, the observation and assignment of the ring signals are often hampered by excessive overlaps and tight spin couplings. These difficulties have been greatly alleviated by using stereo-array isotope labeled (SAIL) proteins, which are composed of isotope-labeled amino acids optimized for unambiguous side-chain NMR assignment, exclusively through the {sup 13}C-{sup 13}C and {sup 13}C-{sup 1}H spin coupling networks (Kainosho et al. in Nature 440:52-57, 2006). In this paper, we propose an alternative type of SAIL-Trp with the [{zeta}2,{zeta}3-{sup 2}H{sub 2}; {delta}1,{epsilon}3,{eta}2-{sup 13}C{sub 3}; {epsilon}1-{sup 15}N]-indole ring ([{sup 12}C{sub {gamma},}{sup 12}C{sub {epsilon}2}] SAIL-Trp), which provides a more robust way to correlate the {sup 1}H{sub {beta}}, {sup 1}H{sub {alpha}}, and {sup 1}H{sub N} to the {sup 1}H{sub {delta}1} and {sup 1}H{sub {epsilon}3} through the intra-residue NOEs. The assignment of the {sup 1}H{sub {delta}1}/{sup 13}C{sub {delta}1} and {sup 1}H{sub {epsilon}3}/{sup 13}C{sub {epsilon}3} signals can thus be transferred to the {sup 1}H{sub {epsilon}1}/{sup 15}N{sub {epsilon}1} and {sup 1}H{sub {eta}2}/{sup 13}C{sub {eta}2} signals, as with the previous type of SAIL-Trp, which has an extra {sup 13}C at the C{sub {gamma}} of the ring. By taking advantage of the stereospecific deuteration of one of the prochiral {beta}-methylene protons, which was {sup 1}H{sub {beta}2} in this experiment, one can determine the side-chain conformation of the Trp residue including the {chi}{sub 2} angle, which is especially important for Trp residues, as they can adopt three preferred conformations. We demonstrated the usefulness of [{sup 12}C{sub {gamma}},{sup 12}C

  5. Alternative SAIL-Trp for robust aromatic signal assignment and determination of the χ2 conformation by intra-residue NOEs

    International Nuclear Information System (INIS)

    Miyanoiri, Yohei; Takeda, Mitsuhiro; Jee, JunGoo; Ono, Akira M.; Okuma, Kosuke; Terauchi, Tsutomu; Kainosho, Masatsune

    2011-01-01

    Tryptophan (Trp) residues are frequently found in the hydrophobic cores of proteins, and therefore, their side-chain conformations, especially the precise locations of the bulky indole rings, are critical for determining structures by NMR. However, when analyzing [U– 13 C, 15 N]-proteins, the observation and assignment of the ring signals are often hampered by excessive overlaps and tight spin couplings. These difficulties have been greatly alleviated by using stereo-array isotope labeled (SAIL) proteins, which are composed of isotope-labeled amino acids optimized for unambiguous side-chain NMR assignment, exclusively through the 13 C– 13 C and 13 C– 1 H spin coupling networks (Kainosho et al. in Nature 440:52–57, 2006). In this paper, we propose an alternative type of SAIL-Trp with the [ζ2,ζ3- 2 H 2 ; δ1,ε3,η2- 13 C 3 ; ε1- 15 N]-indole ring ([ 12 C γ, 12 C ε2 ] SAIL-Trp), which provides a more robust way to correlate the 1 H β , 1 H α , and 1 H N to the 1 H δ1 and 1 H ε3 through the intra-residue NOEs. The assignment of the 1 H δ1 / 13 C δ1 and 1 H ε3 / 13 C ε3 signals can thus be transferred to the 1 H ε1 / 15 N ε1 and 1 H η2 / 13 C η2 signals, as with the previous type of SAIL-Trp, which has an extra 13 C at the C γ of the ring. By taking advantage of the stereospecific deuteration of one of the prochiral β-methylene protons, which was 1 H β2 in this experiment, one can determine the side-chain conformation of the Trp residue including the χ 2 angle, which is especially important for Trp residues, as they can adopt three preferred conformations. We demonstrated the usefulness of [ 12 C γ , 12 C ε2 ] SAIL-Trp for the 12 kDa DNA binding domain of mouse c-Myb protein (Myb-R2R3), which contains six Trp residues.

  6. Alternative SAIL-Trp for robust aromatic signal assignment and determination of the χ(2) conformation by intra-residue NOEs.

    Science.gov (United States)

    Miyanoiri, Yohei; Takeda, Mitsuhiro; Jee, JunGoo; Ono, Akira M; Okuma, Kosuke; Terauchi, Tsutomu; Kainosho, Masatsune

    2011-12-01

    Tryptophan (Trp) residues are frequently found in the hydrophobic cores of proteins, and therefore, their side-chain conformations, especially the precise locations of the bulky indole rings, are critical for determining structures by NMR. However, when analyzing [U-(13)C,(15)N]-proteins, the observation and assignment of the ring signals are often hampered by excessive overlaps and tight spin couplings. These difficulties have been greatly alleviated by using stereo-array isotope labeled (SAIL) proteins, which are composed of isotope-labeled amino acids optimized for unambiguous side-chain NMR assignment, exclusively through the (13)C-(13)C and (13)C-(1)H spin coupling networks (Kainosho et al. in Nature 440:52-57, 2006). In this paper, we propose an alternative type of SAIL-Trp with the [ζ2,ζ3-(2)H(2); δ1,ε3,η2-(13)C(3); ε1-(15)N]-indole ring ([(12)C (γ,) ( 12) C(ε2)] SAIL-Trp), which provides a more robust way to correlate the (1)H(β), (1)H(α), and (1)H(N) to the (1)H(δ1) and (1)H(ε3) through the intra-residue NOEs. The assignment of the (1)H(δ1)/(13)C(δ1) and (1)H(ε3)/(13)C(ε3) signals can thus be transferred to the (1)H(ε1)/(15)N(ε1) and (1)H(η2)/(13)C(η2) signals, as with the previous type of SAIL-Trp, which has an extra (13)C at the C(γ) of the ring. By taking advantage of the stereospecific deuteration of one of the prochiral β-methylene protons, which was (1)H(β2) in this experiment, one can determine the side-chain conformation of the Trp residue including the χ(2) angle, which is especially important for Trp residues, as they can adopt three preferred conformations. We demonstrated the usefulness of [(12)C(γ),(12)C(ε2)] SAIL-Trp for the 12 kDa DNA binding domain of mouse c-Myb protein (Myb-R2R3), which contains six Trp residues.

  7. Ac-Trp-DPhe(p-I)-Arg-Trp-NH2, a 250-Fold Selective Melanocortin-4 Receptor (MC4R) Antagonist over the Melanocortin-3 Receptor (MC3R), Affects Energy Homeostasis in Male and Female Mice Differently.

    Science.gov (United States)

    Lensing, Cody J; Adank, Danielle N; Doering, Skye R; Wilber, Stacey L; Andreasen, Amy; Schaub, Jay W; Xiang, Zhimin; Haskell-Luevano, Carrie

    2016-09-21

    The melanocortin-4 receptor (MC4R) has been indicated as a therapeutic target for metabolic disorders such as anorexia, cachexia, and obesity. The current study investigates the in vivo effects on energy homeostasis of a 15 nM MC4R antagonist SKY2-23-7, Ac-Trp-DPhe(p-I)-Arg-Trp-NH2, that is a 3700 nM melanocortin-3 receptor (MC3R) antagonist with minimal MC3R and MC4R agonist activity. When monitoring both male and female mice in TSE metabolic cages, sex-specific responses were observed in food intake, respiratory exchange ratio (RER), and energy expenditure. A 7.5 nmol dose of SKY2-23-7 increased food intake, increased RER, and trended toward decreasing energy expenditure in male mice. However, this compound had minimal effect on female mice's food intake and RER at the 7.5 nmol dose. A 2.5 nmol dose of SKY2-23-7 significantly increased female food intake, RER, and energy expenditure while having a minimal effect on male mice at this dose. The observed sex differences of SKY2-23-7 administration result in the discovery of a novel chemical probe for elucidating the molecular mechanisms of the sexual dimorphism present within the melanocortin pathway. To further explore the melanocortin sexual dimorphism, hypothalamic gene expression was examined. The mRNA expression of the MC3R and proopiomelanocortin (POMC) were not significantly different between sexes. However, the expression of agouti-related peptide (AGRP) was significantly higher in female mice which may be a possible mechanism for the sex-specific effects observed with SKY2-23-7.

  8. Severe coagulation factor VII deficiency caused by a novel homozygous mutation (p. Trp284Gly) in loop 140s.

    Science.gov (United States)

    Hao, Xiuping; Cheng, XiaoLi; Ye, Jiajia; Wang, Yingyu; Yang, LiHong; Wang, Mingshan; Jin, Yanhui

    2016-06-01

    Congenital coagulation factor VII (FVII) deficiency is a rare disorder caused by mutation in F7 gene. Herein, we reported a patient who had unexplained hematuria and vertigo with consanguineous parents. He has been diagnosed as having FVII deficiency based on the results of reduced FVII activity (2.0%) and antigen (12.8%). The thrombin generation tests verified that the proband has obstacles in producing thrombin. Direct sequencing analysis revealed a novel homozygous missense mutation p.Trp284Gly. Also noteworthy is the fact that the mutational residue belongs to structurally conserved loop 140s, which majorly undergo rearrangement after FVII activation. Model analysis indicated that the substitution disrupts these native hydrophobic interactions, which are of great importance to the conformation in the activation domain of FVIIa.

  9. Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception

    Directory of Open Access Journals (Sweden)

    Giuseppe Mancuso

    2015-10-01

    Full Text Available Ruta graveolens (rue is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels.

  10. Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception.

    Science.gov (United States)

    Mancuso, Giuseppe; Borgonovo, Gigliola; Scaglioni, Leonardo; Bassoli, Angela

    2015-10-16

    Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels.

  11. Proteolysis of His-Phe-Arg-Trp-Pro-Gly-Pro in the blood and brain of rats in vivo.

    Science.gov (United States)

    Shevchenko, K V; Nagaev, I Yu; Babakov, V N; Andreeva, L A; Shevchenko, V P; Radilov, A S; Myasoedov, N F

    2015-01-01

    The kinetics of the content of His-Phe-Arg-Trp-Pro-Gly-Pro (ACTH (6-9)PGP) and its hydrolysis products in the blood and brain of rats in the case of intranasal administration and intravenous injection of tritiated ACTH(6-9)PGP was studied. The parameters of bioavailability of ACTH(6-9)PGP administered intranasally were higher, indicating certain prospects in the intranasal application in clinical practice. We also found that the factor that determines ACTH(6-9)PGP proteolysis in experiments both in vivo and in vitro is aminopeptidases. The main products of ACTH(6-9)PGP during its metabolism in rats are short peptides and amino acids.

  12. Cause finding experiments and environmental analysis on the accident of the fire and explosion in TRP bituminization facility

    International Nuclear Information System (INIS)

    Fujine, Sachio; Murata, Mikio; Abe, Hitoshi

    1999-09-01

    This report is the summary of the cause finding experiments and environmental analysis on the accident of the fire and explosion occurred at March 11th, 1997, in TRP bituminization facility of PNC (Power Reactor and Nuclear Fuel Development Corporation). Regarding the cause finding experiments, chemical components have been analyzed for the effluent samples taken from PNC's facility, bituminized mock waste has been produced using the simulated salt effluent prepared according to the results of chemical analysis, thermal analysis and experiment of runaway exothermic reaction have been conducted using the mock waste, and the component of flammable gases emitted from the heated waste have been collected and analyzed. Regarding environmental analysis on the accident, the amount of radioactive cesium released by the accident has been calculated by the comparative analysis using the atmospheric dispersion simulation code SPEEDI with the data of environmental monitoring and the public dose has been assessed. (author)

  13. Design and studies of multiple mechanism of anti-Candida activity of a new potent Trp-rich peptide dendrimers.

    Science.gov (United States)

    Zielińska, Paulina; Staniszewska, Monika; Bondaryk, Małgorzata; Koronkiewicz, Mirosława; Urbańczyk-Lipkowska, Zofia

    2015-11-13

    Eight peptide dendrimers were designed as structural mimics of natural cationic amphiphilic peptides with antifungal activity and evaluated for their anti-Candida potential against the wild type strains and mutants. Dendrimer 14 containing four Trp residues and dodecyl tail and a slightly smaller dendrimer 9 decorated with four N-methylated Trp that displayed 100 and 99.7% of growth inhibition at 16 μg/mL respectively, were selected for evaluation against the Candida albicans mutants with disabled biosynthesis of aspartic proteases responsible for host tissue colonization and morphogenesis during biofilm formation (sessile model). Flow cytometry method was employed to detect apoptotic cells with membrane alterations (phosphatidylserine translocation), and differentiation of apoptotic from necrotic cells was also performed. Simultaneous staining of cell surface phosphatidylserine with Annexin-V-Fluorescein and necrotic cells with propidium iodide was conducted. 14 at 16 μg/mL caused C. albicans cells to undergo cellular apoptosis but its increasing concentrations induced necrosis. 14 influenced C. albicans biofilm viability as well as hyphal and cell wall morphology. Confocal microscopy and cell wall staining with calcofluor white revealed that in epithelial model the cell surface structure was perturbed at MIC of peptide dendrimer. It appears that tryptophan or 1-methyltryptophan groups displayed at the surface and positive charges hidden in the dendrimer tree along with hydrocarbon tail located at C-terminus are important for the anti-Candida activity since dendrimers containing tryptamine at C-terminus showed only a moderate activity. Our results suggest that membranolytic dendrimer 14, targeting cellular apoptotic pathway and impairing the cell wall formation in mature biofilm, may be a potential multifunctional antifungal lead compound for the control of C. albicans infections. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. TRP 9904 - Constitutive Behavior of High Strength Multiphase Sheel Steel Under High Strain Rate Deformation

    Energy Technology Data Exchange (ETDEWEB)

    David Matlock; John Speer

    2005-03-31

    The focus of the research project was to systematically assess the strain rate dependence of strengthening mechanisms in new advanced high strength sheet steels. Data were obtained on specially designed and produced Duel Phase and TRIP steels and compared to the properties of automotive steels currently in use.

  15. School Improvement Grants: Selected States Generally Awarded Funds Only to Eligible Schools. American Recovery and Reinvestment Act of 2009. Final Audit Report. ED-OIG/A05L0002

    Science.gov (United States)

    US Department of Education, 2012

    2012-01-01

    This final audit report covers the results of the review of five State educational agencies' monitoring plans and awarding processes for American Recovery and Reinvestment Act of 2009 and regular School Improvement Grants funds that the State educational agencies awarded for fiscal year 2009 (for use during school year 2010-2011). The objectives…

  16. Influence of thymine starvation on UV mutability of Escherichia coli B/r Hcr/sup +/ thy/sup -/ trp/sup -/

    Energy Technology Data Exchange (ETDEWEB)

    Balgavy, P; Turek, R [Slovenska Akademia Vied, Bratislava (Czechoslovakia). Vyskumny Ustav Onkologicky

    1976-01-01

    Escherichia coli B/r Hcr/sup +/ thy/sup -/ trp/sup -/ cells were cultivated in a synthetic glucose medium supplemented with 2 ..mu..g/ml thymine and 14 ..mu..g/ml tryptophan until the beginning of the exponential growth phase. After filtration and washing the cells were thymine starved for different periods of time. During short-term starvation (about 40 minutes) the cells did not die and the frequency of Trp/sup +/ revertants as determined on the synthetic glucose medium supplemented with 2 ..mu..g/ml thymine and 0.75 ..mu..g/ml tryptophan solidified with agar did not increase. From the 45th min of starvation cells died exponentially and at the same time the fraction of Trp/sup +/ revertants in the population increased. During short-term starvation the sensitivity of cells to ultraviolet radiation become enhanced, at the same time one could see an increase of frequency of ''mutation-frequency-decline''-stable ultraviolet induced Trp/sup +/ revertants. Is is supposed that short-term thymine starvation affects the coordination of the rec/sup +/ and polAl/sup +/ systems participating in the uvr/sup +/ dependent DNA repair synthesis in favour of the rec/sup +/ system, incidentally starvation may affect the error-free postreplication repair in which the products of the uvr/sup +/ and rec/sup +/ genes participate.

  17. Protective effects of D-Trp6-luteinising hormone-releasing hormone microcapsules against cyclophosphamide-induced gonadotoxicity in female rats.

    Science.gov (United States)

    Bokser, L; Szende, B; Schally, A V

    1990-06-01

    The possible protective effect of an agonist of luteinising hormone-releasing hormone (LH-RH) against the ovarian damage caused by cyclophosphamide was investigated in rats. D-Trp6-LH-RH microcapsules were injected once a month for 3 months, in a dose calculated to release 25 micrograms day-1. Control animals received the injection vehicle. Sixty days after the first injection of microcapsules, cyclophosphamide was given at a loading dose of 50 mg kg-1 followed by 5 mg kg-1 day-1 for 30 days, while the treatment with D-Trp6-LH-RH was continued. When the ovaries were examined 3 months and 5 months after discontinuation of treatment, a significant reduction in the total number of follicles (P less than 0.01) was found in non-pretreated animals given cyclophosphamide. This reduction affected mainly follicles larger than 100 microns. An irreversible disintegration and destruction of granulosa cells was also observed in this group. In animals pretreated with D-Trp6-LH-RH, administration of cyclophosphamide caused no reduction in the number and diameter of follicles. Thus, the treatment with D-Trp6-LH-RH microcapsules before and during chemotherapy prevented the ovarian injury inflicted by cyclophosphamide. The suppression of gonadal function by LH-RH analogues could be possibly utilised for the protection of the ovaries against damage caused by cytotoxic drugs.

  18. Folding Dynamics of the Trp-Cage Miniprotein: Evidence for a Native-Like Intermediate from Combined Time-Resolved Vibrational Spectroscopy and Molecular Dynamics Simulations

    NARCIS (Netherlands)

    Meuzelaar, H.; Marino, K.A.; Huerta-Viga, A.; Panman, M.R.; Smeenk, L.E.J.; Kettelarij, A.J.; van Maarseveen, J.H.; Timmerman, P.; Bolhuis, P.G.; Woutersen, S.

    2013-01-01

    Trp-cage is a synthetic 20-residue miniprotein which folds rapidly and spontaneously to a well-defined globular structure more typical of larger proteins. Due to its small size and fast folding, it is an ideal model system for experimental and theoretical investigations of protein folding

  19. A reassessment of synchronous fluorescence in the separation of Trp and Tyr contributions in protein emission and in the determination of conformational changes

    DEFF Research Database (Denmark)

    Bobone, Sara; van de Weert, Marco; Stella, Lorenzo

    2014-01-01

    solvents, as well as a real protein (bovine serum albumin). Unfortunately, synchronous spectra were found to be unreliable in the separation of Trp and Tyr emission components in proteins. A simple alternative approach based on the deconvolution of emission spectra is presented. In addition, an equation...

  20. Structure-activity relationship studies on a Trp dendrimer with dual activities against HIV and enterovirus A71. Modifications on the amino acid.

    Science.gov (United States)

    Martínez-Gualda, Belén; Sun, Liang; Rivero-Buceta, Eva; Flores, Aida; Quesada, Ernesto; Balzarini, Jan; Noppen, Sam; Liekens, Sandra; Schols, Dominique; Neyts, Johan; Leyssen, Pieter; Mirabelli, Carmen; Camarasa, María-José; San-Félix, Ana

    2017-03-01

    We have recently described a new class of dendrimers with tryptophan (Trp) on the surface that show dual antiviral activities against HIV and EV71 enterovirus. The prototype compound of this family is a pentaerythritol derivative with 12 Trps on the periphery. Here we complete the structure-activity relationship studies of this family to identify key features that might be significant for the antiviral activity. With this aim, novel dendrimers containing different amino acids (aromatic and non-aromatic), tryptamine (a "decarboxylated" analogue of Trp) and N-methyl Trp on the periphery have been prepared. Dendrimer with N-Methyl Trp was the most active against HIV-1 and HIV-2 while dendrimer with tyrosine was endowed with the most potent antiviral activity against EV71. This tyrosine dendrimer proved to inhibit a large panel of EV71 clinical isolates (belonging to different clusters) in the low nanomolar/high picomolar range. In addition, a new synthetic procedure (convergent approach) has been developed for the synthesis of the prototype and some other dendrimers. This convergent approach proved more efficient (higher yields, easier purification) than the divergent approach previously reported. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Direct Binding between Pre-S1 and TRP-like Domains in TRPP Channels Mediates Gating and Functional Regulation by PIP2.

    Science.gov (United States)

    Zheng, Wang; Cai, Ruiqi; Hofmann, Laura; Nesin, Vasyl; Hu, Qiaolin; Long, Wentong; Fatehi, Mohammad; Liu, Xiong; Hussein, Shaimaa; Kong, Tim; Li, Jingru; Light, Peter E; Tang, Jingfeng; Flockerzi, Veit; Tsiokas, Leonidas; Chen, Xing-Zhen

    2018-02-06

    Transient receptor potential (TRP) channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5-bisphosphate (PIP2), with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3 N and C termini (N-C) that is functionally essential. The interaction was mediated by aromatic Trp81 in pre-S1 domain and cationic Lys568 in TRP-like domain. Structure-function analyses revealed similar N-C interaction in TRPP2 as well as TRPM8/-V1/-C4 via highly conserved tryptophan and lysine/arginine residues. PIP2 bound to cationic residues in TRPP3, including K568, thereby disrupting the N-C interaction and negatively regulating TRPP3. PIP2 had similar negative effects on TRPP2. Interestingly, we found that PIP2 facilitates the N-C interaction in TRPM8/-V1, resulting in channel potentiation. The intramolecular N-C interaction might represent a shared mechanism underlying the gating and PIP2 regulation of TRP channels. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Direct Binding between Pre-S1 and TRP-like Domains in TRPP Channels Mediates Gating and Functional Regulation by PIP2

    Directory of Open Access Journals (Sweden)

    Wang Zheng

    2018-02-01

    Full Text Available Transient receptor potential (TRP channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5-bisphosphate (PIP2, with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3 N and C termini (N-C that is functionally essential. The interaction was mediated by aromatic Trp81 in pre-S1 domain and cationic Lys568 in TRP-like domain. Structure-function analyses revealed similar N-C interaction in TRPP2 as well as TRPM8/-V1/-C4 via highly conserved tryptophan and lysine/arginine residues. PIP2 bound to cationic residues in TRPP3, including K568, thereby disrupting the N-C interaction and negatively regulating TRPP3. PIP2 had similar negative effects on TRPP2. Interestingly, we found that PIP2 facilitates the N-C interaction in TRPM8/-V1, resulting in channel potentiation. The intramolecular N-C interaction might represent a shared mechanism underlying the gating and PIP2 regulation of TRP channels.

  3. Associations between Dietary Patterns, ADRβ2 Gln27Glu and ADRβ3 Trp64Arg with Regard to Serum Triglyceride Levels: J-MICC Study

    Directory of Open Access Journals (Sweden)

    Hinako Nanri

    2016-09-01

    Full Text Available Interactions between dietary patterns and 2 β-adrenergic receptor (ADRβ gene polymorphisms (ADRβ2 Gln27Glu and ADRβ3 Trp64Arg were examined with regard to the effects on serum triglyceride levels. The cross-sectional study comprised 1720 men and women (aged 35–69 years enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC Study. Genotyping was conducted using a multiplex polymerase chain reaction-based invader assay. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. We identified four dietary patterns: healthy, Western, seafood and bread patterns. There was no significant association between any dietary pattern and serum triglyceride levels. After a separate genotype-based analysis, significant interactions between ADRβ3 Trp64Arg genotype and the bread pattern (p for interaction = 0.01 were associated with serum triglyceride levels; specifically, after adjusting for confounding factors, Arg allele carriers with the bread pattern had lower serum triglycerides (p for trend = 0.01. However, the Trp/Trp homozygous subjects with the bread pattern showed no association with serum triglycerides (p for trend = 0.55. Interactions between other dietary patterns and ADRβ polymorphisms were not significant for serum triglyceride levels. Our findings suggest that ADRβ3 polymorphism modifies the effects of the bread pattern on triglyceride levels.

  4. [Mutation in the beta3-adrenergic receptor gene (Trp64Arg) does not influence insulin resistence, energy metabolism, fat distribution and lipid spectrum in young people. Pilot study].

    Science.gov (United States)

    Bendlová, B; Mazura, I; Vcelák, J; Pelikánová, T; Kunesová, M; Hainer, V; Obenberger, J; Palyzová, D

    1999-05-01

    A missence mutation Trp64Arg in the beta3-adrenergic receptor gene is associated with obesity, insulin resistance, a lower metabolic rate and the earlier onset of NIDDM but the published results are controversial. We investigated the effect of this mutation on insulin resistance (euglycemic hyperinsulinemic clamp), on fat mass and fat distribution (anthropometry, bioimpedance, CT) and resting metabolic rate (indirect calorimetry), lipid spectrum and other metabolic disturbances in Czech juveniles recruited from juvenile hypertensives (H, n = 68) and controls (C, n = 81). The frequency of this mutation (determined by digestion of 210 bp PCR product with MvaI) was double in H than in C (14.7%, vs. 7.4%) and the carriers of Arg64 allele had sig. higher fasting glucose (H: p = 0.002. C: p = 0.025). Four Trp64/Arg64 and six Trp64/Trp64 men (age 23 +/- 4.2, vs. 22.5 +/- 1.9 y, BMI 26 +/- 5.5, vs. 22.9 +/- 5.1 kg/m2) took part in a detailed pilot study. But no signif. differences (Horn's method) in fasting glucose (4.6 +/- 0.6, vs. 4.9 +/- 0.4 mmol/l), in parameters of insulin resistance (M-value150-180 min. 9.1 +/- 1.1, vs. 8.9 +/- 1.5 mg glucose/kg.min(-1)), resting metabolic rate/lean body mass (RMR/kg LBM: 78.6 +/- 4.6, vs. 85.6 +/- 23.2 kJ/kg), lipid spectrum and other screened parameters were found. The lowest resting metabolic rate (RMR/kg LBM 55.4; 62.6 kJ/kg) was found in brothers (both C, Trp64/Trp64) who highly differ in body constitution (BMI 19.0 resp. 32.4 kg/m2). We suppose that in this case the energy metabolism is probably determined by other genetic loci and does not correlate with body fat mass. Our pilot study does not confirm the influence of Trp64Arg mutation in heterozygous carriers on insulin resistance, energy metabolism and lipid spectrum.

  5. D-TRP(8-γMSH Prevents the Effects of Endotoxin in Rat Skeletal Muscle Cells through TNFα/NF-KB Signalling Pathway.

    Directory of Open Access Journals (Sweden)

    Ana Belén Gómez-SanMiguel

    Full Text Available Sepsis induces anorexia and muscle wasting secondary to an increase in muscle proteolysis. Melanocyte stimulating hormones (MSH is a family of peptides that have potent anti-inflammatory effects. Melanocortin receptor-3 (MC3-R has been reported as the predominant anti-inflammatory receptor for melanocortins. The aim of this work was to analyse whether activation of MC3-R, by administration of its agonist D-Trp(8-γMSH, is able to modify the response of skeletal muscle to inflammation induced by lipopolysaccharide endotoxin (LPS or TNFα. Adult male rats were injected with 250 μg/kg LPS and/or 500 μg/kg D-Trp(8-γMSH 17:00 h and at 8:00 h the following day, and euthanized 4 hours afterwards. D-Trp(8-γMSH decreased LPS-induced anorexia and prevented the stimulatory effect of LPS on hypothalamic IL-1β, COX-2 and CRH as well as on serum ACTH and corticosterone. Serum IGF-I and its expression in liver and gastrocnemius were decreased in rats injected with LPS, but not in those that also received D-Trp(8-γMSH. However, D-Trp(8-γMSH was unable to modify the effect of LPS on IGFBP-3. In the gastrocnemius D-Trp(8-γMSH blocked LPS-induced decrease in pAkt, pmTOR, MHC I and MCH II, as well as the increase in pNF-κB(p65, FoxO1, FoxO3, LC3b, Bnip-3, Gabarap1, atrogin-1, MuRF1 and in LC3a/b lipidation. In L6 myotube cultures, D-Trp(8-γMSH was able to prevent TNFα-induced increase of NF-κB(p65 phosphorylation and decrease of Akt phosphorylation as well as of IGF-I and MHC I expression. These data suggest that MC3-R activation prevents the effect of endotoxin on skeletal wasting by modifying inflammation, corticosterone and IGF-I responses and also by directly acting on muscle cells through the TNFα/NF-κB(p65 pathway.

  6. TRP channels in brown and white adipogenesis from human progenitors: new therapeutic targets and the caveats associated with the common antibiotic, streptomycin.

    Science.gov (United States)

    Goralczyk, Anna; van Vijven, Marc; Koch, Mathilde; Badowski, Cedric; Yassin, M Shabeer; Toh, Sue-Anne; Shabbir, Asim; Franco-Obregón, Alfredo; Raghunath, Michael

    2017-08-01

    Transient receptor potential (TRP) channels are polymodal cell sensors responding to diverse stimuli and widely implicated in the developmental programs of numerous tissues. The evidence for an involvement of TRP family members in adipogenesis, however, is scant. We present the first comprehensive expression profile of all known 27 human TRP genes in mesenchymal progenitors cells during white or brown adipogenesis. Using positive trilineage differentiation as an exclusion criterion, TRP polycystic (P)3, and TPR melastatin (M)8 were found to be uniquely adipospecific. Knockdown of TRPP3 repressed the expression of the brown fat signature genes uncoupling protein (UCP)-1 and peroxisome proliferator-activated receptor γ coactivator (PGC)-1α as well as attenuated forskolin-stimulated uncoupled respiration. However, indices of generalized adipogenesis, such as lipid droplet morphology and fatty acid binding protein (FAPB)-4 expression, were not affected, indicating a principal mitochondrial role of TRPP3. Conversely, activating TRPM8 with menthol up-regulated UCP-1 expression and augmented uncoupled respiration predominantly in white adipocytes (browning), whereas streptomycin antagonized TRPM8-mediated calcium entry, downregulated UCP-1 expression, and mitigated uncoupled respiration; menthol was less capable of augmenting uncoupled respiration (thermogenesis) in brown adipocytes. TRPP3 and TRPM8 hence appear to be involved in the priming of mitochondria to perform uncoupled respiration downstream of adenylate cyclase. Our results also underscore the developmental caveats of using antibiotics in adipogenic studies.-Goralczyk, A., van Vijven, M., Koch, M., Badowski, C., Yassin, M. S., Toh, S.-A., Shabbir, A., Franco-Obregón, A., Raghunath, M. TRP channels in brown and white adipogenesis from human progenitors: new therapeutic targets and the caveats associated with the common antibiotic, streptomycin. © FASEB.

  7. Replica exchange simulation of reversible folding/unfolding of the Trp-cage miniprotein in explicit solvent: on the structure and possible role of internal water.

    Science.gov (United States)

    Paschek, Dietmar; Nymeyer, Hugh; García, Angel E

    2007-03-01

    We simulate the folding/unfolding equilibrium of the 20-residue miniprotein Trp-cage. We use replica exchange molecular dynamics simulations of the AMBER94 atomic detail model of the protein explicitly solvated by water, starting from a completely unfolded configuration. We employ a total of 40 replicas, covering the temperature range between 280 and 538 K. Individual simulation lengths of 100 ns sum up to a total simulation time of about 4 micros. Without any bias, we observe the folding of the protein into the native state with an unfolding-transition temperature of about 440 K. The native state is characterized by a distribution of root mean square distances (RMSD) from the NMR data that peaks at 1.8A, and is as low as 0.4A. We show that equilibration times of about 40 ns are required to yield convergence. A folded configuration in the entire extended ensemble is found to have a lifetime of about 31 ns. In a clamp-like motion, the Trp-cage opens up during thermal denaturation. In line with fluorescence quenching experiments, the Trp-residue sidechain gets hydrated when the protein opens up, roughly doubling the number of water molecules in the first solvation shell. We find the helical propensity of the helical domain of Trp-cage rather well preserved even at very high temperatures. In the folded state, we can identify states with one and two buried internal water molecules interconnecting parts of the Trp-cage molecule by hydrogen bonds. The loss of hydrogen bonds of these buried water molecules in the folded state with increasing temperature is likely to destabilize the folded state at elevated temperatures.

  8. Impaired 8-Hydroxyguanine Repair Activity of MUTYH Variant p.Arg109Trp Found in a Japanese Patient with Early-Onset Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Kazuya Shinmura

    2014-01-01

    Full Text Available Purpose. The biallelic inactivation of the 8-hydroxyguanine repair gene MUTYH leads to MUTYH-associated polyposis (MAP, which is characterized by colorectal multiple polyps and carcinoma(s. However, only limited information regarding MAP in the Japanese population is presently available. Since early-onset colorectal cancer (CRC is a characteristic of MAP and might be caused by the inactivation of another 8-hydroxyguanine repair gene, OGG1, we investigated whether germline MUTYH and OGG1 mutations are involved in early-onset CRC in Japanese patients. Methods. Thirty-four Japanese patients with early-onset CRC were examined for germline MUTYH and OGG1 mutations using sequencing. Results. Biallelic pathogenic mutations were not found in any of the patients; however, a heterozygous p.Arg19*  MUTYH variant and a heterozygous p.Arg109Trp MUTYH variant were detected in one patient each. The p.Arg19* and p.Arg109Trp corresponded to p.Arg5* and p.Arg81Trp, respectively, in the type 2 nuclear-form protein. The defective DNA repair activity of p.Arg5* is apparent, while that of p.Arg81Trp has been demonstrated using DNA cleavage and supF forward mutation assays. Conclusion. These results suggest that biallelic MUTYH or OGG1 pathogenic mutations are rare in Japanese patients with early-onset CRC; however, the p.Arg19* and p.Arg109Trp MUTYH variants are associated with functional impairments.

  9. Histidine 352 (His352 and tryptophan 355 (Trp355 are essential for flax UGT74S1 glucosylation activity toward secoisolariciresinol.

    Directory of Open Access Journals (Sweden)

    Kaushik Ghose

    Full Text Available Flax secoisolariciresinol diglucoside (SDG lignan is a natural phytoestrogen for which a positive role in metabolic diseases is emerging. Until recently however, much less was known about SDG and its monoglucoside (SMG biosynthesis. Lately, flax UGT74S1 was identified and characterized as an enzyme sequentially glucosylating secoisolariciresinol (SECO into SMG and SDG when expressed in yeast. However, the amino acids critical for UGT74S1 glucosyltransferase activity were unknown. A 3D structural modeling and docking, site-directed mutagenesis of five amino acids in the plant secondary product glycosyltransferase (PSPG motif, and enzyme assays were conducted. UGT74S1 appeared to be structurally similar to the Arabidopsis thaliana UGT72B1 model. The ligand docking predicted Ser357 and Trp355 as binding to the phosphate and hydroxyl groups of UDP-glucose, whereas Cys335, Gln337 and Trp355 were predicted to bind the 7-OH, 2-OCH3 and 17-OCH3 of SECO. Site-directed mutagenesis of Cys335, Gln337, His352, Trp355 and Ser357, and enzyme assays revealed an alteration of these binding sites and a significant reduction of UGT74S1 glucosyltransferase catalytic activity towards SECO and UDP-glucose in all mutants. A complete abolition of UGT74S1 activity was observed when Trp355 was substituted to Ala355 and Gly355 or when changing His352 to Asp352, and an altered metabolite profile was observed in Cys335Ala, Gln337Ala, and Ser357Ala mutants. This study provided for the first time evidence that Trp355 and His352 are critical for UGT74S1's glucosylation activity toward SECO and suggested the possibility for SMG production in vitro.

  10. A Comparative History of Department of Defense Management Reform from 1947 to 2005

    Science.gov (United States)

    2006-12-01

    Initiative START Strategic Arms Reduction Treaty xix TRP Technology Reinvestment Project T&E Testing and Evaluation TOC Total Ownership Cost TAV Total...don’t tell" policy for sexual orientation. While he wanted to shrink the Navy and the overall force structure, he understood the value and necessity...Department had initiated: a smaller workforce, fewer organizations, manage suppliers, focus on total ownership cost ( TOC ), establish and execute

  11. A Feasibility Study of Steelmaking by Molten Oxide Electrolysis (TRP9956)

    Energy Technology Data Exchange (ETDEWEB)

    Donald R. Sadoway; Gerbrand Ceder

    2009-12-31

    Molten oxide electrolysis (MOE) is an extreme form of molten salt electrolysis, a technology that has been used to produce tonnage metals for over 100 years - aluminum, magnesium, lithium, sodium and the rare earth metals specifically. The use of carbon-free anodes is the distinguishing factor in MOE compared to other molten salt electrolysis techniques. MOE is totally carbon-free and produces no CO or CO2 - only O2 gas at the anode. This project is directed at assessing the technical feasibility of MOE at the bench scale while determining optimum values of MOE operating parameters. An inert anode will be identified and its ability to sustain oxygen evalution will be demonstrated.

  12. Inter-genomic displacement via lateral gene transfer of bacterial trp operons in an overall context of vertical genealogy

    Directory of Open Access Journals (Sweden)

    Keyhani Nemat O

    2004-06-01

    Full Text Available Abstract Background The growing conviction that lateral gene transfer plays a significant role in prokaryote genealogy opens up a need for comprehensive evaluations of gene-enzyme systems on a case-by-case basis. Genes of tryptophan biosynthesis are frequently organized as whole-pathway operons, an attribute that is expected to facilitate multi-gene transfer in a single step. We have asked whether events of lateral gene transfer are sufficient to have obscured our ability to track the vertical genealogy that underpins tryptophan biosynthesis. Results In 47 complete-genome Bacteria, the genes encoding the seven catalytic domains that participate in primary tryptophan biosynthesis were distinguished from any paralogs or xenologs engaged in other specialized functions. A reliable list of orthologs with carefully ascertained functional roles has thus been assembled and should be valuable as an annotation resource. The protein domains associated with primary tryptophan biosynthesis were then concatenated, yielding single amino-acid sequence strings that represent the entire tryptophan pathway. Lateral gene transfer of several whole-pathway trp operons was demonstrated by use of phylogenetic analysis. Lateral gene transfer of partial-pathway trp operons was also shown, with newly recruited genes functioning either in primary biosynthesis (rarely or specialized metabolism (more frequently. Conclusions (i Concatenated tryptophan protein trees are congruent with 16S rRNA subtrees provided that the genomes represented are of sufficiently close phylogenetic spacing. There are currently seven tryptophan congruency groups in the Bacteria. Recognition of a succession of others can be expected in the near future, but ultimately these should coalesce to a single grouping that parallels the 16S rRNA tree (except for cases of lateral gene transfer. (ii The vertical trace of evolution for tryptophan biosynthesis can be deduced. The daunting complexities engendered

  13. Interstate Electrification Improvement Project

    Energy Technology Data Exchange (ETDEWEB)

    Puckette, Margaret [Shorepower Technologies, Hillsboro, OR (United States); Kim, Jeff [Shorepower Technologies, Hillsboro, OR (United States)

    2015-07-01

    The Interstate Electrification Improvement Project, publicly known as the Shorepower Truck Electrification Project (STEP), started in May 2011 and ended in March 2015. The project grant was awarded by the Department of Energy’s Vehicles Technology Office in the amount of $22.2 million. It had three overarching missions: 1. Reduce the idling of Class 8 tractors when parked at truck stops, to reduce diesel fuel consumption and thus U.S. dependence on foreign petroleum; 2. Stimulate job creation and economic activity as part of the American Reinvestment and Recovery Act of 2009; 3. Reduce greenhouse gas emissions (GHG) from diesel combustion and the carbon footprint of the truck transportation industry. The project design was straightforward. First, build fifty Truck Stop Electrification (TSE) facilities in truck stop parking lots across the country so trucks could plug-in to 110V, 220V, or 480VAC, and shut down the engine instead of idling. These facilities were strategically located at fifty truck stops along major U.S. Interstates with heavy truck traffic. Approximately 1,350 connection points were installed, including 150 high-voltage electric standby Transport Refrigeration Unit (eTRU) plugs--eTRUs are capable of plugging in to shore power1 to cool the refrigerated trailer for loads such as produce, meats and ice cream. Second, the project provided financial incentives on idle reduction equipment to 5,000 trucks in the form of rebates, to install equipment compatible with shore power. This equipment enables drivers to shut down the main engine when parked, to heat or cool their cab, charge batteries, or use other household appliances without idling—a common practice that uses approximately 1 gallon of diesel per hour. The rebate recipients were intended to be the first fleets to plug into Shorepower to save diesel fuel and ensure there is significant population of shore power capable trucks. This two part project was designed to complement each other by

  14. Acupuncture Alleviates Colorectal Hypersensitivity and Correlates with the Regulatory Mechanism of TrpV1 and p-ERK

    Directory of Open Access Journals (Sweden)

    Shao-Jun Wang

    2012-01-01

    Full Text Available Here we used a mouse model of zymosan-induced colorectal hypersensitivity, a similar model of IBS in our previous work, to evaluate the effectiveness of the different number of times of acupuncture and elucidate its potential mechanism of EA treatment. Colorectal distension (CRD tests show that intracolonic zymosan injection does, while saline injection does not, induce a typical colorectal hypersensitivity. EA treatment at classical acupoints Zusanli (ST36 and Shangjuxu (ST37 in both hind limbs for 15 min slightly attenuated and significantly blunted the hypersensitive responses after first and fifth acupunctures, respectively, to colorectal distention in zymosan treatment mice, but not in saline treatment mice. Western blot results indicated that ion channel and TrpV1 expression in colorectum as well as ERK1/2 MAPK pathway activation in peripheral and central nerve system might be involved in this process. Hence, we conclude that EA is a potential therapeutic tool in the treatment and alleviation of chronic abdominal pain, and the effectiveness of acupuncture analgesia is accumulative with increased number of times of acupuncture when compared to that of a single time of acupuncture.

  15. The Variant p.(Arg183Trp) in SPTLC2 Causes Late-Onset Hereditary Sensory Neuropathy.

    Science.gov (United States)

    Suriyanarayanan, Saranya; Auranen, Mari; Toppila, Jussi; Paetau, Anders; Shcherbii, Maria; Palin, Eino; Wei, Yu; Lohioja, Tarja; Schlotter-Weigel, Beate; Schön, Ulrike; Abicht, Angela; Rautenstrauss, Bernd; Tyynismaa, Henna; Walter, Maggie C; Hornemann, Thorsten; Ylikallio, Emil

    2016-03-01

    Hereditary sensory and autonomic neuropathy 1 (HSAN1) is an autosomal dominant disorder that can be caused by variants in SPTLC1 or SPTLC2, encoding subunits of serine palmitoyl-CoA transferase. Disease variants alter the enzyme's substrate specificity and lead to accumulation of neurotoxic 1-deoxysphingolipids. We describe two families with autosomal dominant HSAN1C caused by a new variant in SPTLC2, c.547C>T, p.(Arg183Trp). The variant changed a conserved amino acid and was not found in public variant databases. All patients had a relatively mild progressive distal sensory impairment, with onset after age 50. Small fibers were affected early, leading to abnormalities on quantitative sensory testing. Sural biopsy revealed a severe chronic axonal neuropathy with subtotal loss of myelinated axons, relatively preserved number of non-myelinated fibers and no signs for regeneration. Skin biopsy with PGP9.5 labeling showed lack of intraepidermal nerve endings early in the disease. Motor manifestations developed later in the disease course, but there was no evidence of autonomic involvement. Patients had elevated serum 1-deoxysphingolipids, and the variant protein produced elevated amounts of 1-deoxysphingolipids in vitro, which proved the pathogenicity of the variant. Our results expand the genetic spectrum of HSAN1C and provide further detail about the clinical characteristics. Sequencing of SPTLC2 should be considered in all patients presenting with mild late-onset sensory-predominant small or large fiber neuropathy.

  16. Modified melanocortin tetrapeptide Ac-His-dPhe-Arg-Trp-NH at the arginine side chain with ureas and thioureas.

    Science.gov (United States)

    Joseph, C G; Sorensen, N B; Wood, M S; Xiang, Z; Moore, M C; Haskell-Luevano, C

    2005-11-01

    The Ac-His-dPhe-Arg-Trp-NH2 tetrapeptide is a nonselective melanocortin agonist and replacement of Arg in the tetrapeptide with acidic, basic or neutral amino acids results in reduced potency at the melanocortin receptor (MCR) isoforms (MC1R and MC3-5R). To determine the importance of the positive charge and the guanidine moiety for melanocortin activity, a series of urea- and thiourea-substituted tetrapeptides were designed. Replacement of Arg with Lys or ornithine reduced agonist activity at the mouse mMC1 and mMC3-5 receptors, thus supporting the hypothesis that the guanidine moiety is important for receptor potency, particularly at the MC3-5 receptors. The Arg side chain-modified tetrapeptides examined in this study include substituted phenyl, naphthyl, and aliphatic urea and thiourea residues using a Lys side-chain template. These ligands elicit full-agonist pharmacology at the mouse MCRs examined in this study.

  17. Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site

    Energy Technology Data Exchange (ETDEWEB)

    Lanekoff, Ingela; Cha, Jeeyeon; Kyle, Jennifer E.; Dey, Sudhansu K.; Laskin, Julia; Burnum-Johnson, Kristin E.

    2016-09-13

    Here we demonstrate that conditional deletion of mouse uterine Trp53 (p53d/d), molecularly linked to mTORC1 activation and causally linked to premature uterine senescence and preterm birth, results in aberrant lipid signatures within the heterogeneous cell types of embryo implantation sites on day 8 of pregnancy. In situ nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) was used to characterize the molecular speciation of free fatty acids, monoacylglycerols, unmodified and oxidized phosphatidylcholine (PC/Ox-PC), and diacylglycerol (DG) species within implantation sites of p53d/d mice and floxed littermates. Implantation sites from p53d/d mice exhibited distinct spatially resolved changes demonstrating accumulation of DG species, depletion of Ox-PC species, and increase in species with more unsaturated acyl chains, including arachidonic and docosahexaenoic acid. Understanding abnormal changes in the abundance and localization of individual lipid species early in the progression to premature birth is important for discovering novel targets for treatments and diagnosis.

  18. Involvement of Atm and Trp53 in neural cell loss due to Terf2 inactivation during mouse brain development.

    Science.gov (United States)

    Kim, Jusik; Choi, Inseo; Lee, Youngsoo

    2017-11-01

    Maintenance of genomic integrity is one of the critical features for proper neurodevelopment and inhibition of neurological diseases. The signals from both ATM and ATR to TP53 are well-known mechanisms to remove neural cells with DNA damage during neurogenesis. Here we examined the involvement of Atm and Atr in genomic instability due to Terf2 inactivation during mouse brain development. Selective inactivation of Terf2 in neural progenitors induced apoptosis, resulting in a complete loss of the brain structure. This neural loss was rescued partially in both Atm and Trp53 deficiency, but not in an Atr-deficient background in the mouse. Atm inactivation resulted in incomplete brain structures, whereas p53 deficiency led to the formation of multinucleated giant neural cells and the disruption of the brain structure. These giant neural cells disappeared in Lig4 deficiency. These data demonstrate ATM and TP53 are important for the maintenance of telomere homeostasis and the surveillance of telomere dysfunction during neurogenesis.

  19. NMR assignments for the amino-terminal residues of trp repressor and their role in DNA binding

    International Nuclear Information System (INIS)

    Arrowsmith, C.H.; Carey, J.; Treat-Clemons, L.; Jardetzky, O.

    1989-01-01

    The trp repressor of Escherichia coli specifically binds to operator DNAs in three operons involved in tryptophan metabolism. The NMR spectra of repressor and a chymotryptic fragment lacking the six amino-terminal residues are compared. Two-dimensional J-correlated spectra of the two forms of the protein are superimposable except for cross-peaks that are associated with the N-terminal region. The chemical shifts and relaxation behavior of the N-terminal resonances suggest mobile arms. Spin-echo experiments on a ternary complex of repressor with L-tryptophan and operator DNA indicate that the termini are also disordered in the complex, although removal of the arms reduces the DNA binding energy. Relaxation measurements on the armless protein show increased mobility for several residues, probably due to helix fraying in the newly exposed N-terminal region. DNA binding by the armless protein does not reduce the mobility of these residues. Thus, it appears that the arms serve to stabilize the N-terminal helix but that this structural role does not explain their contribution to the DNA binding energy. These results suggest that the promiscuous DNA binding by the arms seen in the X-ray crystal structure is found in solution as well

  20. Preparation of human Melanocortin-4 receptor agonist libraries: linear peptides X-Y-DPhe7-Arg8-Trp(or 2-Nal)9-Z-NH2.

    Science.gov (United States)

    Cheung, Adrian Wai-Hing; Qi, Lida; Gore, Vijay; Chu, Xin-Jie; Bartkovitz, David; Kurylko, Grazyna; Swistok, Joseph; Danho, Waleed; Chen, Li; Yagaloff, Keith

    2005-12-15

    Two libraries of hMC4R agonists, X-Y-DPhe(7)-Arg(8)-2-Nal(9)-Z-NH(2) and X-Y-DPhe(7)-Arg(8)-Trp(9)-Z-NH(2), totaling 185 peptides were prepared using Irori radiofrequency tagging technology and Argonaut Quest 210 Synthesizer, where X stands for N-caps, Y for His(6) surrogates and Z for Gly(10) surrogates. As a result of this study, His-modified pentapeptides with Trp were found to be more hMC4R potent than the corresponding 2-Nal analogs, novel N-caps and Gly surrogates were identified and 19 new peptides which are potent hMC4R agonists (EC(50) 1-15nM) and selective against hMC1R were discovered.

  1. Structure-activity relationship of linear tetrapeptides Tic-DPhe-Arg-Trp-NH2 at the human melanocortin-4 receptor and effects on feeding behaviors in rat.

    Science.gov (United States)

    Ye, Zhixiong; MacNeil, Tanya; Weinberg, David H; Kalyani, Rubana N; Tang, Rui; Strack, Alison M; Murphy, Beth A; Mosley, Ralph T; Euan MacIntyre, D; Van der Ploeg, Lex H T; Patchett, Arthur A; Wyvratt, Matthew J; Nargund, Ravi P

    2005-10-01

    The melanocortin subtype-4 receptor (MC4R) has been implicated in the control of feeding behavior and body weight regulation. A series of tetrapeptides, based on Tic-DPhe-Arg-Trp-NH2-a mimic of the putative message sequence "His-Phe-Arg-Trp" and modified at the DPhe position, were prepared and pharmacologically characterized for potency and selectivity. Substitution of His with Tic gave peptides with significant increases in selectivity. The effects of the substitution pattern of DPhe were investigated and it has significant influences on potency and the level of the maximum cAMP accumulation. Intracerebroventricular administration of peptide 10 induced significant inhibition of cumulative overnight food intake and feeding duration in rats.

  2. Effect of Zingiber officinale Supplementation on Obesity Management with Respect to the Uncoupling Protein 1 -3826A>G and ß3-adrenergic Receptor Trp64Arg Polymorphism.

    Science.gov (United States)

    Ebrahimzadeh Attari, Vahideh; Asghari Jafarabadi, Mohammad; Zemestani, Maryam; Ostadrahimi, Alireza

    2015-07-01

    The present study aimed to investigate the effect of ginger (Zingiber officinale) supplementation on some obesity-associated parameters, with nutrigenetics approach. Accordingly, 80 eligible obese women (aged 18-45 years) were randomly assigned to receive either ginger (2-g ginger rhizomes powder as two 1-g tablets per day) or placebo supplements (corn starch with the same amount) for 12 weeks. Subjects were tested for changes in body weight, body mass index, waist and hip circumferences, body composition, appetite score, and dietary intake. Moreover, participants were genotyped for the -3826A>G and Trp64Arg polymorphisms of uncoupling protein 1 and ß3-adrenergic receptor genes, respectively. Over 12 weeks, ginger supplementation resulted in a slight but statistically significant decrease in all anthropometric measurements and total appetite score as compared with placebo group, which were more pronounced in subjects with the AA genotype for uncoupling protein 1 and Trp64Trp genotype for ß3-adrenergic receptor gene. However, there was no significant difference in changes of body composition and total energy and macronutrients intake between groups. In conclusion, our findings suggest that ginger consumption has potential in managing obesity, accompanying with an intervention-genotype interaction effect. However, further clinical trials need to explore ginger's efficacy as an anti-obesity agent in the form of powder, extract, or its active components. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Resistance mutations of Pro197, Asp376 and Trp574 in the acetohydroxyacid synthase (AHAS) affect pigments, growths, and competitiveness of Descurainia sophia L.

    Science.gov (United States)

    Zhang, Yongzhi; Xu, Yufang; Wang, Shipeng; Li, Xuefeng; Zheng, Mingqi

    2017-11-27

    D. Sophia is one of the most problematic weed species infesting winter wheat in China, and has evolved high resistance to tribenuron-methyl. Amino acid substitutions at site of Pro197, Asp376 and Trp574 in acetohydroxyacid synthase (AHAS) were mainly responsible for D. sophia resistance to tribenuron-methyl. In this study, D. sophia plant individually homozygous for specific AHAS mutation (Pro197Leu, Pro197His, Pro197Ser, Pro197Thr, Asp376Glu and Trp574Leu) were generated. In addition, the effects of resistance mutations on pigments, growths and competitiveness of susceptible (S) and resistant (R) plants of D. sophia were investigated. The results indicated the R plants carrying Pro197Leu or Pro197His or Asp376Glu or Trp574Leu displayed stronger competitiveness than S plants. The adverse effects on R plants aggravated with the increase of R plants proportion, which made the R plants against domination the weed community in absent of herbicide selection. Therefore, these resistance mutation have no obvious adverse effects on the pigments (chlorophyll a, chlorophyll b and carotenoid), relative growth rates (RGR), leaf area ratio (LAR) and net assimilation rate (NAR) of R plants.

  4. Characterisation of the novel deleterious RAD51C p.Arg312Trp variant and prioritisation criteria for functional analysis of RAD51C missense changes.

    Science.gov (United States)

    Gayarre, Javier; Martín-Gimeno, Paloma; Osorio, Ana; Paumard, Beatriz; Barroso, Alicia; Fernández, Victoria; de la Hoya, Miguel; Rojo, Alejandro; Caldés, Trinidad; Palacios, José; Urioste, Miguel; Benítez, Javier; García, María J

    2017-09-26

    Despite a high prevalence of deleterious missense variants, most studies of RAD51C ovarian cancer susceptibility gene only provide in silico pathogenicity predictions of missense changes. We identified a novel deleterious RAD51C missense variant (p.Arg312Trp) in a high-risk family, and propose a criteria to prioritise RAD51C missense changes qualifying for functional analysis. To evaluate pathogenicity of p.Arg312Trp variant we used sequence homology, loss of heterozygosity (LOH) and segregation analysis, and a comprehensive functional characterisation. To define a functional-analysis prioritisation criteria, we used outputs for the known functionally confirmed deleterious and benign RAD51C missense changes from nine pathogenicity prediction algorithms. The p.Arg312Trp variant failed to correct mitomycin and olaparib hypersensitivity and to complement abnormal RAD51C foci formation according to functional assays, which altogether with LOH and segregation data demonstrated deleteriousness. Prioritisation criteria were based on the number of predictors providing a deleterious output, with a minimum of 5 to qualify for testing and a PredictProtein score greater than 33 to assign high-priority indication. Our study points to a non-negligible number of RAD51C missense variants likely to impair protein function, provides a guideline to prioritise and encourage their selection for functional analysis and anticipates that reference laboratories should have available resources to conduct such assays.

  5. Alpha-adducin Gly460Trp polymorphism and hypertension risk: a meta-analysis of 22 studies including 14303 cases and 15961 controls.

    Directory of Open Access Journals (Sweden)

    Kuo Liu

    Full Text Available BACKGROUND: No clear consensus has been reached on the alpha-adducin polymorphism (Gly460Trp and essential hypertension risk. We performed a meta-analysis in an effort to systematically summarize the possible association. METHODOLOGY/PRINCIPAL FINDINGS: Studies were identified by searching MEDLINE and EMBASE databases complemented with perusal of bibliographies of retrieved articles and correspondence with original authors. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. We selected 22 studies that met the inclusion criteria including a total of 14303 hypertensive patients and 15961 normotensive controls. Overall, the 460Trp allele showed no statistically significant association with hypertension risk compared to Gly460 allele (P = 0.69, OR = 1.02, 95% CI 0.94-1.10, P(heterogeneity<0.0001 in all subjects. Meta-analysis under other genetic contrasts still did not reveal any significant association in all subjects, Caucasians, East Asians and others. The results were similar but heterogeneity did not persist when sensitivity analyses were limited to these studies. CONCLUSIONS/SIGNIFICANCE: Our meta-analysis failed to provide evidence for the genetic association of α-adducin gene Gly460Trp polymorphism with hypertension. Further studies investigating the effect of genetic networks, environmental factors, individual biological characteristics and their mutual interactions are needed to elucidate the possible mechanism for hypertension in humans.

  6. A novel amino acid substitution Trp574Arg in acetolactate synthase (ALS) confers broad resistance to ALS-inhibiting herbicides in crabgrass (Digitaria sanguinalis).

    Science.gov (United States)

    Li, Jian; Li, Mei; Gao, Xingxiang; Fang, Feng

    2017-12-01

    Crabgrass (Digitaria sanguinalis) is an annual monocotyledonous weed. In recent years, field applications of nicosulfuron have been ineffective in controlling crabgrass populations in Shandong Province, China. To investigate the mechanisms of resistance to nicosulfuron in crabgrass populations, the acetolactate synthase (ALS) gene fragment covering known resistance-confering mutation sites was amplified and sequenced. Dose-response experiments suggested that the resistant population SD13 (R) was highly resistant to nicosulfuron (resistance index R/S = 43.7) compared with the sensitive population SD22 (S). ALS gene sequencing revealed a Trp574Arg substitution in the SD13 population, and no other known resistance-conferring mutations were found. In vitro ALS enzyme assays further confirmed that the SD13 population was resistant to all tested ALS-inhibiting herbicides. The resistance pattern experiments revealed that, compared with SD22, the SD13 population exhibited broad-spectrum resistance to nicosulfuron (43.7-fold), imazethapyr (11.4-fold) and flumetsulam (16.1-fold); however, it did not develop resistance to atrazine, mesotrione and topramezone. This study demonstrated that Trp574Arg substitution was the main reason for crabgrass resistance to ALS-inhibiting herbicides. To our knowledge, this is the first report of Trp574Arg substitution in a weed species, and is the first report of target-site mechanisms of herbicide resistance for crabgrass. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  7. Project Plan Remote Target Fabrication Refurbishment Project

    International Nuclear Information System (INIS)

    Bell, Gary L.; Taylor, Robin D.

    2009-01-01

    was received in July 2009 under the Remote Target Fabrication Refurbishment Task of the Enhanced Utilization of Isotope Facilities project (Project Identification Code 2005230) funded by the American Recovery and Reinvestment Act of 2009. The goal of this project is to recover the capability to produce 4-5 curium targets for the irradiation period starting with HFIR cycle 427, currently scheduled to begin 2/17/10. Assuming success, the equipment would then be used to fabricate 6-7 additional targets to hold for the next irradiation campaign specified by the program. Specific objectives are the return to functionality of the Cubicle 3 Pellet Fabrication Line; Cubicle 2 Target Assembly equipment; and Cubicle 1 Target Inspection and Final Assembly system.

  8. Community Renewable Energy Deployment Provides Replicable Examples of Clean Energy Projects (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2012-09-01

    This fact sheet describes the U.S. Department of Energy's Community Renewable Energy Deployment (CommRE) program, which is a more than $20 million effort funded through the American Recovery and Reinvestment Act of 2009, to promote investment in clean energy solutions and provide real-life examples for other local governments, campuses, and small utilities to replicate. Five community-based renewable energy projects received funding from DOE through the CommRE and their progress is detailed.

  9. Modular Organization of the NusA- and NusG-Stimulated RNA Polymerase Pause Signal That Participates in the Bacillus subtilis trp Operon Attenuation Mechanism.

    Science.gov (United States)

    Mondal, Smarajit; Yakhnin, Alexander V; Babitzke, Paul

    2017-07-15

    The Bacillus subtilis trpEDCFBA operon is regulated by a transcription attenuation mechanism in which tryptophan-activated TRAP binds to the nascent transcript and blocks the formation of an antiterminator structure such that the formation of an overlapping intrinsic terminator causes termination in the 5' untranslated region (5' UTR). In the absence of bound TRAP, the antiterminator forms and transcription continues into the trp genes. RNA polymerase pauses at positions U107 and U144 in the 5' UTR. The general transcription elongation factors NusA and NusG stimulate pausing at both positions. NusG-stimulated pausing at U144 requires sequence-specific contacts with a T tract in the nontemplate DNA (ntDNA) strand within the paused transcription bubble. Pausing at U144 participates in a trpE translation repression mechanism. Since U107 just precedes the critical overlap between the antiterminator and terminator structures, pausing at this position is thought to participate in attenuation. Here we carried out in vitro pausing and termination experiments to identify components of the U107 pause signal and to determine whether pausing affects the termination efficiency in the 5' UTR. We determined that the U107 and U144 pause signals are organized in a modular fashion containing distinct RNA hairpin, U-tract, and T-tract components. NusA-stimulated pausing was affected by hairpin strength and the U-tract sequence, whereas NusG-stimulated pausing was affected by hairpin strength and the T-tract sequence. We also determined that pausing at U107 results in increased TRAP-dependent termination in the 5' UTR, implying that NusA- and NusG-stimulated pausing participates in the trp operon attenuation mechanism by providing additional time for TRAP binding. IMPORTANCE The expression of several bacterial operons is controlled by regulated termination in the 5' untranslated region (5' UTR). Transcription attenuation is defined as situations in which the binding of a regulatory

  10. Rifampicin and chloramphenicol effects on DNA replication in ultraviolet-damaged Escherichia coli B/r WP2 thy trp

    International Nuclear Information System (INIS)

    Doudney, C.O.

    1976-01-01

    The antibiotic rifampicin, which blocks specifically RNA synthesis, limited DNA replication in Escherichia coli strain B/r WP2 thy trp after an increase of about 50% when added to the incubation medium at the time of replication initiation after ultraviolet fluences of 20 J/m 2 or 25 J/m 2 . Chloramphenicol, which blocks protein synthesis, did not limit DNA replication when added at initiation or any time after. The prolonged lag in DNA replication caused by ultraviolet was not itself responsible for the rifampicin limitation. When a lag of 30 min was caused by starvation for thymine, DNA was synthesized after readdition of thymine to an increase of 100% or more in rifampicin-containing medium. When chloramphenicol was added to an ultraviolet-exposed culture, the limiting effect of rifampicin alone was suppressed. This effect held even with a higher fluence (32.5 J/m 2 ), after which the ability to make DNA in the presence of rifampicin alone was slight. Maximum effect was obtained when the chloramphenicol was added to the ultraviolet-exposed, rifampicin-containing culture immediately before initiation of DNA replication. When rifampicin was present at a concentration of 150 μg/ml (2.2 x 10 -4 M), 3 μg/ml of chloramphenicol (9.2 x 10 -6 M) was as effective as 160 μg/ml (5.0 x 10 -4 M), thus eliminating the possibility that direct stoichiometric interaction of rifampicin and chloramphenicol molecules caused the effect

  11. Phosphoinositide-interacting regulator of TRP (PIRT) has opposing effects on human and mouse TRPM8 ion channels.

    Science.gov (United States)

    Hilton, Jacob K; Salehpour, Taraneh; Sisco, Nicholas J; Rath, Parthasarathi; Van Horn, Wade D

    2018-05-03

    Transient receptor potential melastatin 8 (TRPM8) is a cold-sensitive ion channel with diverse physiological roles. TRPM8 activity is modulated by many mechanisms, including an interaction with the small membrane protein phosphoinositide-interacting regulator of TRP (PIRT). Here, using comparative electrophysiology experiments, we identified species-dependent differences between the human and mouse TRPM8-PIRT complexes. We found that human PIRT attenuated human TPRM8 conductance, unlike mouse PIRT, which enhanced mouse TRPM8 conductance. Quantitative western blot analysis demonstrates that this effect does not arise from decreased trafficking of TRPM8 to the plasma membrane. Chimeric human/mouse TRPM8 channels were generated to probe the molecular basis of the PIRT modulation, and the effect was recapitulated in a pore domain chimera, demonstrating the importance of this region for PIRT-mediated regulation of TRPM8. Moreover, recombinantly expressed and purified human TRPM8 S1-S4 domain (comprising transmembrane helices S1-S4, also known as the sensing domain, ligand-sensing domain, or voltage sensing-like domain) and full-length human PIRT were used to investigate binding between the proteins. NMR experiments, supported by a pulldown assay, indicated that PIRT binds directly and specifically to the TRPM8 S1-S4 domain. Binding became saturated as the S1-S4:PIRT mole ratio approached 1. Our results have uncovered species-specific TRPM8 modulation by PIRT. They provide evidence for a direct interaction between PIRT and the TRPM8 S1-S4 domain with a 1:1 binding stoichiometry, suggesting that a functional tetrameric TRPM8 channel has four PIRT-binding sites. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Discovery of melanocortin ligands via a double simultaneous substitution strategy based on the Ac-His-DPhe-Arg-Trp-NH2 template.

    Science.gov (United States)

    Todorovic, Aleksandar; Lensing, Cody J; Holder, Jerry Ryan; Scott, Joseph W; Sorensen, Nicholas B; Haskell-Luevano, Carrie

    2018-05-21

    The melanocortin system regulates an array of diverse physiological functions including pigmentation, feeding behavior, energy homeostasis, cardiovascular regulation, sexual function, and steroidogenesis. Endogenous melanocortin agonist ligands all possess the minimal messaging tetrapeptide sequence His-Phe-Arg-Trp. Based on this endogenous sequence, the Ac-His1-DPhe2-Arg3-Trp4-NH 2 tetrapeptide has previously been shown to be a useful scaffold when utilizing traditional positional scanning approaches to modify activity at the various melanocortin receptors (MC1-5R). The study reported herein was undertaken to evaluate a double simultaneous substitution strategy as an approach to further diversify the Ac-His1-DPhe2-Arg3-Trp4-NH 2 tetrapeptide with concurrent introduction of natural and unnatural amino acids at positions 1, 2, or 4 as well as an octanoyl residue at the N-terminus. The designed library includes the following combinations: (A) double simultaneous substitution at capping group position (Ac) together with position 1, 2, or 4, (B) double simultaneous substitution at position 1 and 2, (C) double simultaneous substitution at position 1 and 4, and (D) double simultaneous substitution at position 2 and 4. Several lead ligands with unique pharmacologies were discovered in the current study including antagonists targeting the neuronal mMC3R with minimal agonist activity and ligands with selective profiles for the various melanocortin subtypes. The results suggest that the double simultaneous substitution strategy is a suitable approach in altering melanocortin receptor potency, selectivity, or converting agonists into antagonists and vice versa.

  13. Evidence for the functional involvement of members of the TRP channel family in the uptake of Na(+) and NH4 (+) by the ruminal epithelium.

    Science.gov (United States)

    Rosendahl, Julia; Braun, Hannah S; Schrapers, Katharina T; Martens, Holger; Stumpff, Friederike

    2016-08-01

    Large quantities of protein are degraded in the fermentative parts of the gut to ammonia, which is absorbed, detoxified to urea, and excreted, leading to formation of nitrogenous compounds such as N2O that are associated with global warming. In ruminants, channel-mediated uptake of NH4 (+) from the rumen predominates. The molecular identity of these channels remains to be clarified. Ruminal cells and epithelia from cows and sheep were investigated using patch clamp, Ussing chamber, microelectrode techniques, and qPCR. In patch clamp experiments, bovine ruminal epithelial cells expressed a conductance for NH4 (+) that could be blocked in a voltage-dependent manner by divalent cations. In the native epithelium, NH4 (+) depolarized the apical potential, acidified the cytosol and induced a rise in short-circuit current (I sc) that persisted after the removal of Na(+), was blocked by verapamil, enhanced by the removal of divalent cations, and was sensitive to certain transient receptor potential (TRP) channel modulators. Menthol or thymol stimulated the I sc in Na(+) or NH4 (+) containing solutions in a dose-dependent manner and modulated transepithelial Ca(2+) fluxes. On the level of messenger RNA (mRNA), ovine and bovine ruminal epithelium expressed TRPA1, TRPV3, TRPV4, TRPM6, and TRPM7, with any expression of TRPV6 marginal. No bands were detected for TRPV1, TRPV5, or TRPM8. Functional and molecular biological data suggest that the transport of NH4 (+), Na(+), and Ca(2+) across the rumen involves TRP channels, with TRPV3 and TRPA1 emerging as prime candidate genes. TRP channels may also contribute to the transport of NH4 (+) across other epithelia.

  14. TrpA1 activation in peripheral sensory neurons underlies the ionic basis of pain hypersensitivity in response to vinca alkaloids.

    Directory of Open Access Journals (Sweden)

    Nina Boiko

    Full Text Available Chemotherapy induced peripheral neuropathy (CIPN, a side effect of many anti-cancer drugs including the vinca alkaloids, is characterized by a severe pain syndrome that compromises treatment in many patients. Currently there are no effective treatments for this pain syndrome except for the reduction of anti-cancer drug dose. Existing data supports the model that the pain associated with CIPN is the result of anti-cancer drugs augmenting the function of the peripheral sensory nociceptors but the cellular mechanisms underlying the effects of anti-cancer drugs on sensory neuron function are not well described. Studies from animal models have suggested a number of disease etiologies including mitotoxicity, axonal degeneration, immune signaling, and reduced sensory innervations but these outcomes are the result of prolonged treatment paradigms and do not necessarily represent the early formative events associated with CIPN. Here we show that acute exposure to vinca alkaloids results in an immediate pain syndrome in both flies and mice. Furthermore, we demonstrate that exposure of isolated sensory neurons to vinca alkaloids results in the generation of an inward sodium current capable of depolarizing these neurons to threshold resulting in neuronal firing. These neuronal effects of vinca alkaloids require the transient receptor potential ankyrin-1 (TrpA1 channel, and the hypersensitization to painful stimuli in response to the acute exposure to vinca alkaloids is reduced in TrpA1 mutant flies and mice. These findings demonstrate the direct excitation of sensory neurons by CIPN-causing chemotherapy drugs, and identify TrpA1 as an important target during the pathogenesis of CIPN.

  15. Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: arginine substitution.

    Science.gov (United States)

    Cheung, Adrian Wai-Hing; Danho, Waleed; Swistok, Joseph; Qi, Lida; Kurylko, Grazyna; Franco, Lucia; Yagaloff, Keith; Chen, Li

    2002-09-02

    A series of pentapeptides, based on Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) and modified at the Arg(8) position, was prepared and pharmacologically characterized. Peptides containing either cyanoguanidine or acylguanidine, two substantially less basic arginine surrogates, were found to retain the agonist activity of the parent peptide at both hMC1R and hMC4R. This study unequivocally shows that the positive charge of Arg(8) is not essential for efficient interactions of our pentapeptide with both hMC1R and hMC4R.

  16. The MECP2 variant c.925C>T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome

    DEFF Research Database (Denmark)

    Schönewolf-Greulich, Bitten; Tejada, Maria-Isabel; Stephens, K

    2016-01-01

    . Intriguingly, the mother of an affected male patient is an asymptomatic carrier of this variant. It is therefore likely that the p.(Arg309Trp) variation does not necessarily lead to male lethality, and it results in a wide range of clinical features in females, probably influenced by different X......-pair substitution affecting Arg309 at the C-terminal end of the transcriptional repression domain (TRD). All patients have intellectual disability and present with some RTT features, but they do not fulfill the clinical criteria for typical or atypical RTT. Most of the patients also have mild facial dysmorphism...

  17. 76 FR 184 - Notice of Buy American Waiver Under the American Recovery and Reinvestment Act of 2009

    Science.gov (United States)

    2011-01-03

    ... the iron, steel, and manufactured goods used in the project are produced in the United States.'' The..., the ARRV is likely to be deployed to Arctic and Antarctic waters, the north Pacific and north Atlantic... high polar regions (north and south), as well as the Gulf of Alaska, the north Pacific and the north...

  18. A Trp53fl/flPtenfl/fl mouse model of undifferentiated pleomorphic sarcoma mediated by adeno-Cre injection and in vivo bioluminescence imaging.

    Directory of Open Access Journals (Sweden)

    Marisa R Buchakjian

    Full Text Available Genetic mouse models of soft tissue sarcoma provide critical insights into disease pathophysiology, which are oftentimes unable to be extracted from human tumor samples or xenograft models. In this study we describe a mouse model of soft tissue sarcoma mediated by adenoviral-Cre recombinase injection into Trp53fl/fl/Ptenfl/fl lox-stop-lox luciferase mice. Injection of adenovirus expressing Cre recombinase, either subcutaneously or intramuscularly in two experimental groups, results in viral infection and gene recombination with 100% penetrance within the first 24 hours following injection. Luciferase expression measured by real-time bioluminescence imaging increases over time, with an initial robust increase following viral injection, followed by a steady rise over the next several weeks as primary tumors develop and grow. Intramuscular injections were more commonly associated with evidence of systemic viral distribution than subcutaneous injections. All mice developed soft tissue sarcomas at the primary injection site, with histological examination identifying 93% of tumors as invasive pleomorphic sarcomas based on microscopic morphology and immunohistochemical expression of sarcoma markers. A lymphocytic infiltrate was present in 64% of the sarcomas in this immunocompetent model and 71% of tumors expressed PD-L1. This is the first report of a viral-Cre mediated Trp53/Pten mouse model of undifferentiated pleomorphic sarcoma. The bioluminescence imaging feature, along with high penetrance of the model and its immunological characteristics, makes it suited for pre-clinical studies of soft tissue sarcoma.

  19. Structure-activity relationship of cyclic peptide penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2) at the human melanocortin-1 and -4 receptors: His(6) substitution.

    Science.gov (United States)

    Cheung, Adrian Wai-Hing; Danho, Waleed; Swistok, Joseph; Qi, Lida; Kurylko, Grazyna; Rowan, Karen; Yeon, Mitch; Franco, Lucia; Chu, Xin-Jie; Chen, Li; Yagaloff, Keith

    2003-04-07

    A series of MT-II related cyclic peptides, based on potent but non-selective hMC4R agonist (Penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2)) was prepared in which His(6) residue was systematically substituted. Two of the most interesting peptides identified in this study are Penta-c[Asp-5-ClAtc-DPhe-Arg-Trp-Lys]-NH(2) and Penta-c[Asp-5-ClAtc-DPhe-Cit-Trp-Lys]-NH(2) which are potent hMC4R agonists and are either inactive or weak partial agonists (not tested for their antagonist activities) in hMC1R, hMC3R and hMC5R agonist assays.

  20. Final Project Closeout Report for Sprint Hydrogen Fuel Cell (HFC) Deployment Project in California, Gulf Coast and Eastern Seaboard Markets

    Energy Technology Data Exchange (ETDEWEB)

    Kenny, Kevin [Sprint, Reston, VA (United States); Bradley, Dwayne [Burns & McDonnell, Kansas City, MO (United States)

    2015-09-01

    Sprint is one of the telecommunications industry leaders in the deployment of hydrogen fuel cell (HFC) systems to provide backup power for their mission critical wireless network facilities. With several hundred fuel cells commissioned in California, states in the gulf coast region, and along the upper eastern seaboard. A strong incentive for advancing the integration of fuel cells into the Sprint network came through the award of a Department of Energy (DOE) grant focused on Market Transformation activities for project (EE0000486). This grant was funded by the 2009 American Recovery and Reinvestment Act (ARRA). The funding provided by DOE ($7.295M) was allocated to support the installation of 260 new HFC systems, equipped with an on-site refillable Medium Pressure Hydrogen Storage Solution (MPHSS), as well as for the conversion of 21 low pressure hydrogen systems to the MPHSS, in hopes of reducing barriers to market acceptance.

  1. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH(2) at the mouse melanocortin receptors: part 2 modifications at the Phe position.

    Science.gov (United States)

    Holder, Jerry Ryan; Bauzo, Rayna M; Xiang, Zhimin; Haskell-Luevano, Carrie

    2002-07-04

    The melanocortin pathway is an important participant in skin pigmentation, steroidogenesis, obesity, energy homeostasis and exocrine gland function. The centrally located melanocortin-3 and melanocortin-4 receptors (MC3R, MC4R) are involved in the metabolic and food intake aspects of energy homeostasis and are stimulated by melanocortin agonists such as alpha-melanocyte stimulation hormone (alpha-MSH). The melanocortin agonists contain the putative message sequence "His-Phe-Arg-Trp," and it has been well-documented that inversion of chirality of the Phe to DPhe results in a dramatic increase in melanocortin receptor potency. Herein, we report a tetrapeptide library, based upon the template Ac-His-DPhe-Arg-Trp-NH(2), consisting of 26 members that have been modified at the DPhe(7) position (alpha-MSH numbering) and pharmacologically characterized for agonist and antagonist activity at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R. The most notable results of this study include the identification of the tetrapeptide Ac-His-(pI)DPhe-Arg-Trp-NH(2) that is a full nanomolar agonist at the mMC1 and mMC5 receptors, a mMC3R partial agonist with potent antagonist activity (pA(2) = 7.25, K(i) = 56 nM) and, but unexpectedly, is a potent agonist at the mMC4R (EC(50) = 25 nM). This ligand possesses novel melanocortin receptor pharmacology, as compared to previously reported peptides, and is potentially useful for in vivo studies to differentiate MC3R vs MC4R physiological roles in animal models, such as primates, where "knockout" animals are not viable options. The DNal(2') substitution for DPhe resulted in a mMC3R partial agonist with antagonist activity (pA(2) = 6.5, K(i) = 295 nM) and a mMC4R (pA(2) = 7.8, K(i) = 17 nM) antagonist possessing 60- and 425-fold decreased potency, respectively, as compared with SHU9119 at these receptors. Examination of this DNal(2')-containing tetrapeptide at the F254S and F259S mutant mMC4Rs resulted in agonist activity of this m

  2. A fungal P450 (CYP5136A3 capable of oxidizing polycyclic aromatic hydrocarbons and endocrine disrupting alkylphenols: role of Trp(129 and Leu(324.

    Directory of Open Access Journals (Sweden)

    Khajamohiddin Syed

    Full Text Available The model white rot fungus Phanerochaete chrysosporium, which is known for its versatile pollutant-biodegradation ability, possesses an extraordinarily large repertoire of P450 monooxygenases in its genome. However, the majority of these P450s have hitherto unknown function. Our initial studies using a genome-wide gene induction strategy revealed multiple P450s responsive to individual classes of xenobiotics. Here we report functional characterization of a cytochrome P450 monooxygenase, CYP5136A3 that showed common responsiveness and catalytic versatility towards endocrine-disrupting alkylphenols (APs and mutagenic/carcinogenic polycyclic aromatic hydrocarbons (PAHs. Using recombinant CYP5136A3, we demonstrated its oxidation activity towards APs with varying alkyl side-chain length (C3-C9, in addition to PAHs (3-4 ring size. AP oxidation involves hydroxylation at the terminal carbon of the alkyl side-chain (ω-oxidation. Structure-activity analysis based on a 3D model indicated a potential role of Trp(129 and Leu(324 in the oxidation mechanism of CYP5136A3. Replacing Trp(129 with Leu (W129L and Phe (W129F significantly diminished oxidation of both PAHs and APs. The W129L mutation caused greater reduction in phenanthrene oxidation (80% as compared to W129F which caused greater reduction in pyrene oxidation (88%. Almost complete loss of oxidation of C3-C8 APs (83-90% was observed for the W129L mutation as compared to W129F (28-41%. However, the two mutations showed a comparable loss (60-67% in C9-AP oxidation. Replacement of Leu(324 with Gly (L324G caused 42% and 54% decrease in oxidation activity towards phenanthrene and pyrene, respectively. This mutation also caused loss of activity towards C3-C8 APs (20-58%, and complete loss of activity toward nonylphenol (C9-AP. Collectively, the results suggest that Trp(129 and Leu(324 are critical in substrate recognition and/or regio-selective oxidation of PAHs and APs. To our knowledge, this is the first

  3. A Trp474Cys mutation in the alpha-subunit of beta-hexosaminidase causes a subacute encephalopathic form of G{sub M2} gangliosidosis, type 1

    Energy Technology Data Exchange (ETDEWEB)

    Petroulakis, E.; Cao, Z.; Salo, T. [Univ. of Manitoba, Winnipeg (Canada)] [and others

    1994-09-01

    Mutations in the HEXA gene that encodes the {alpha}-subunit of the heterodimeric lysosomal enzyme {beta}-hexosaminidase A, or Hex A ({alpha}{beta}), cause G{sub M2} gangliosidosis, type 1. The infantile form (Tay-Sachs disease) results when there is no residual Hex A activity, while less severe and more variable clinical phenotypes result when residual Hex A activity is present. A non-Jewish male who presented with an acute psychotic episode at age 16 was diagnosed with a subacute encephalopathic form of G{sub M2} gangliosidosis. At age 19, chronic psychosis with intermittent acute exacerbations remains the most disabling symptom in this patient and his affected brother although both exhibit some ataxia and moderately severe dysarthria. We have found a 4 bp insertion (+TATC 1278) associated with infantile Tay-Sachs disease on one allele; no previously identified mutation was found on the second allele. SSCP analysis detected a shift in exon 13 and sequencing revealed a G1422C mutation in the second allele that results in a Trp474Cys substitution. The presence of the mutation was confirmed by the loss of HaeIII and ScrFI sites in exon 13 PCR products from the subjects and their father. The mutation was introduced into the {alpha}-subunit cDNA and Hex S ({alpha}{alpha}) and Hex A ({alpha}{beta}) were transiently expressed in monkey COS-7 cells. The Trp474Cys mutant protein had approximately 5% and 12% of wild-type Hex S and Hex A activity, respectively. Western blot analysis revealed a small amount of residual mature {alpha}-subunit and a normal level of precursor protein. We conclude that the Trp474Cys mutation is the cause of the Hex A deficiency associated with a subacute (juvenile-onset) phenotype in this patient. Like other mutations in exon 13 of HEXA, it appears to affect intracellular processing. Studies of the defect in intracellular processing are in progress.

  4. A novel method for the biosynthesis of deuterated proteins with selective protonation at the aromatic rings of Phe, Tyr and Trp

    International Nuclear Information System (INIS)

    Rajesh, Sundaresan; Nietlispach, Daniel; Nakayama, Hiroshi; Takio, Koji; Laue, Ernest D.; Shibata, Takehiko; Ito, Yutaka

    2003-01-01

    A novel biosynthetic strategy is described for the preparation of deuterated proteins containing protons at the ring carbons of Phe, Tyr and Trp, using the aromatic amino acid precursor shikimic acid. Specific protonation at aromatic side chains, with complete deuteration at C α/β positions was achieved in proteins overexpressed in bacteria grown in shikimate-supplemented D 2 O medium. Co-expression of a shikimate transporter in prototrophic bacteria resulted in protonation levels of 62-79%, whereas complete labeling was accomplished using shikimate auxotrophic bacteria. Our labeling protocol permits the measurement of important aromatic side chain derived distance restraints in perdeuterated proteins that could be utilized to enhance the accuracy of NMR structures calculated using low densities of NOEs from methyl selectively protonated samples

  5. Modification of UV-induced mutation frequency and cell survival of Escherichia coli B/r WP2 trpE65 by treatment before irradiation

    International Nuclear Information System (INIS)

    Doudney, C.O.; Rinaldi, C.N.

    1984-01-01

    The UV radiation survival curve of exponentially growing cultures of Escherichia coli B/r WP2 trpE65 was modified by pretreatment for short incubation periods (up to 20 min) with chloramphenicol such that an extended exponential section of intermediate slope appeared between the shoulder and the final exponential slope. Surges of mutation to tryptophan independence occurred with each increase in slope of the survival curve. These surges were separated by extended sections of little mutation. Nalidixic acid prevented both the changes in survival and mutation. Mutation curves obtained with overnight cultures had three extended sections of little mutation alternating with section of high mutation. Reincubation for 60 min in fresh medium reduced or eliminated the low-response sections. These reappeared after 80 to 90 min, when DNA had doubled in the culture and before the initial synchronous cell divisions had occurred. Nalidixic acid prevented this reappearance

  6. A substance P antagonist, [D-Pro2, D-Trp7,9]SP, inhibits inflammatory responses in the rabbit eye

    International Nuclear Information System (INIS)

    Holmdahl, G.; Hakanson, R.; Leander, S.; Rosell, S.; Folkers, K.; Sundler, F.

    1981-01-01

    Neurogenic factors released by antidromic nerve stimulation are thought to be in part responsible for the vasodilation and breakdown of the blood-aqueous barrier that follows trauma to the eye. Substance P is one candidate for the mediation of the inflammatory response since it is thought to be a neurotransmitter in sensory afferents and since exogenous substance P is capable of eliciting a response characteristic of inflammation. In rabbits, intravitreal or topical application onto the eye of a specific substance P antagonist, [d-Pro2, D-Trp7,9]SP, inhibited not only the irritant effects of exogenous substance P but also the inflammatory response to a standardized trauma (infrared irradiation of the iris). These observations suggest that substance P, or a related peptide, is a neurogenic mediator of the inflammatory response in the eye

  7. Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2 induces penile erection via brain and spinal melanocortin receptors.

    Science.gov (United States)

    Wessells, H; Hruby, V J; Hackett, J; Han, G; Balse-Srinivasan, P; Vanderah, T W

    2003-01-01

    Penile erection induced by alpha-melanocyte-stimulating hormone and melanocortin receptors (MC-R) in areas of the spinal cord and periphery has not been demonstrated. To elucidate sites of the proerectile action of melanocortin peptides, in awake male rats we administered the MC-R agonist Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH(2) (MT-II) i.c.v., intrathecal (i.th.) and i.v. and scored penile erection and yawning. Injection of the MC-R antagonist Ac-Nle-c[Asp-His-DNal(2')-Arg-Trp-Lys]-NH(2) (SHU-9119) i.c.v. or i.th. in combination with i.th. MT-II differentiated spinal from supraspinal effects. To exclude a site of action in the penis, we recorded intracavernous pressure responses to intracavernosal injection of MT-II in the anesthetized rat.I.c.v., i.th., and i.v. MT-II induced penile erections in a dose-dependent fashion. Yawning was observed with i.c.v. and i.v. MT-II, while spinal injection did not produce this behavior. Intrathecal delivery of MT-II to the lumbosacral spinal cord was more efficacious in inducing erections than i.c.v. or i.v. administration; SHU-9119 blocked the erectile responses to i.th. MT-II when injected i.th. but not i.c.v. Intracavernosal MT-II neither increased intracavernous pressure nor augmented neurostimulated erectile responses. We confirmed the central proerectile activity of MT-II and demonstrated that in addition to a site of action in the brain, the distal spinal cord contains melanocortin receptors that can initiate penile erection independent of higher centers. These results provide new insight into the central melanocortinergic pathways that mediate penile erection and may allow for more efficacious melanotropin-based therapy for erectile dysfunction.

  8. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 at the mouse melanocortin receptors. Part 3: modifications at the Arg position.

    Science.gov (United States)

    Holder, Jerry Ryan; Xiang, Zhimin; Bauzo, Rayna M; Haskell-Luevano, Carrie

    2003-01-01

    The melanocortin pathway is involved in the regulation of several physiological functions including skin pigmentation, steroidogenesis, obesity, energy homeostasis, and exocrine gland function. This melanocortin pathway consists of five known G-protein coupled receptors, endogenous agonists derived from the proopiomelanocortin (POMC) gene transcript, the endogenous antagonists Agouti and the Agouti-related protein (AGRP) and signals through the intracellular cAMP signal transduction pathway. The melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R) located in the brain are implicated as participating in the metabolic and food intake aspects of energy homeostasis and are stimulated by melanocortin agonists such as alpha-melanocyte stimulation hormone (alpha-MSH). All the endogenous (POMC-derived) melanocortin agonists contain the putative message sequence "His-Phe-Arg-Trp." Herein, we report 12 tetrapeptides, based upon the template Ac-His(6)-DPhe(7)-Arg(8)-Trp(9)-NH(2) (alpha-MSH numbering) that have been modified at the Arg(8) position by neutral, basic, or acidic amino acid side chains. These peptides have been pharmacologically characterized for agonist activity at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R. The most notable results of this study include the observation that removal of the guanidinyl side chain moiety results in decreased melanocortin receptor potency, but that this Arg(8) side chain is not critical for melanocortin receptor agonist activity. Additionally, incorporation of the homoArg(8) residue results in 56-fold MC4R versus MC3R selectivity, and the Orn(8) residue results in 123-fold MC4R versus MC5R and 63-fold MC5R versus MC3R selectivity. Copyright 2002 Elsevier Science Inc.

  9. The Broken Ring: Reduced Aromaticity in Lys-Trp Cations and High pH Tautomer Correlates with Lower Quantum Yield and Shorter Lifetimes

    Science.gov (United States)

    2015-01-01

    Several nonradiative processes compete with tryptophan fluorescence emission. The difficulty in spectral interpretation lies in associating specific molecular environmental features with these processes and thereby utilizing the fluorescence spectral data to identify the local environment of tryptophan. Here, spectroscopic and molecular modeling study of Lys-Trp dipeptide charged species shows that backbone-ring interactions are undistinguished. Instead, quantum mechanical ground state isosurfaces reveal variations in indole π electron distribution and density that parallel charge (as a function of pK1, pK2, and pKR) on the backbone and residues. A pattern of aromaticity-associated quantum yield and fluorescence lifetime changes emerges. Where quantum yield is high, isosurfaces have a charge distribution similar to the highest occupied molecular orbital (HOMO) of indole, which is the dominant fluorescent ground state of the 1La transition dipole moment. Where quantum yield is low, isosurface charge distribution over the ring is uneven, diminished, and even found off ring. At pH 13, the indole amine is deprotonated, and Lys-Trp quantum yield is extremely low due to tautomer structure that concentrates charge on the indole amine; the isosurface charge distribution bears scant resemblance to the indole HOMO. Such greatly diminished fluorescence has been observed for proteins where the indole nitrogen is hydrogen bonded, lending credence to the association of aromaticity changes with diminished quantum yield in proteins as well. Thus tryptophan ground state isosurfaces are an indicator of indole aromaticity, signaling the partition of excitation energy between radiative and nonradiative processes. PMID:24882092

  10. Chronic DNA Replication Stress Reduces Replicative Lifespan of Cells by TRP53-Dependent, microRNA-Assisted MCM2-7 Downregulation.

    Directory of Open Access Journals (Sweden)

    Gongshi Bai

    2016-01-01

    Full Text Available Circumstances that compromise efficient DNA replication, such as disruptions to replication fork progression, cause a state known as DNA replication stress (RS. Whereas normally proliferating cells experience low levels of RS, excessive RS from intrinsic or extrinsic sources can trigger cell cycle arrest and senescence. Here, we report that a key driver of RS-induced senescence is active downregulation of the Minichromosome Maintenance 2-7 (MCM2-7 factors that are essential for replication origin licensing and which constitute the replicative helicase core. Proliferating cells produce high levels of MCM2-7 that enable formation of dormant origins that can be activated in response to acute, experimentally-induced RS. However, little is known about how physiological RS levels impact MCM2-7 regulation. We found that chronic exposure of primary mouse embryonic fibroblasts (MEFs to either genetically-encoded or environmentally-induced RS triggered gradual MCM2-7 repression, followed by inhibition of replication and senescence that could be accelerated by MCM hemizygosity. The MCM2-7 reduction in response to RS is TRP53-dependent, and involves a group of Trp53-dependent miRNAs, including the miR-34 family, that repress MCM expression in replication-stressed cells before they undergo terminal cell cycle arrest. miR-34 ablation partially rescued MCM2-7 downregulation and genomic instability in mice with endogenous RS. Together, these data demonstrate that active MCM2-7 repression is a physiologically important mechanism for RS-induced cell cycle arrest and genome maintenance on an organismal level.

  11. A Lys-Trp cation-π interaction mediates the dimerization and function of the chloride intracellular channel protein 1 transmembrane domain.

    Science.gov (United States)

    Peter, Bradley; Polyansky, Anton A; Fanucchi, Sylvia; Dirr, Heini W

    2014-01-14

    Chloride intracellular channel protein 1 (CLIC1) is a dual-state protein that can exist either as a soluble monomer or in an integral membrane form. The oligomerization of the transmembrane domain (TMD) remains speculative despite it being implicated in pore formation. The extent to which electrostatic and van der Waals interactions drive folding and association of the dimorphic TMD is unknown and is complicated by the requirement of interactions favorable in both aqueous and membrane environments. Here we report a putative Lys37-Trp35 cation-π interaction and show that it stabilizes the dimeric form of the CLIC1 TMD in membranes. A synthetic 30-mer peptide comprising a K37M TMD mutant was examined in 2,2,2-trifluoroethanol, sodium dodecyl sulfate micelles, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes using far-ultraviolet (UV) circular dichroism, fluorescence, and UV absorbance spectroscopy. Our data suggest that Lys37 is not implicated in the folding, stability, or membrane insertion of the TMD peptide. However, removal of this residue impairs the formation of dimers and higher-order oligomers. This is accompanied by a 30-fold loss of chloride influx activity, suggesting that dimerization modulates the rate of chloride conductance. We propose that, within membranes, individual TMD helices associate via a Lys37-mediated cation-π interaction to form active dimers. The latter findings are also supported by results of modeling a putative TMD dimer conformation in which Lys37 and Trp35 form cation-π pairs at the dimer interface. Dimeric helix bundles may then associate to form fully active ion channels. Thus, within a membrane-like environment, aromatic interactions involving a polar lysine side chain provide a thermodynamic driving force for helix-helix association.

  12. The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients--the EUGENE2 study

    DEFF Research Database (Denmark)

    Boesgaard, T W; Zilinskaite, J; Vänttinen, M

    2008-01-01

    AIMS/HYPOTHESIS: A recent genome-wide association study identified the SLC30A8 rs13266634 polymorphism encoding an Arg325Trp polymorphism in the zinc transporter protein member 8 (ZnT-8) to be associated with type 2 diabetes. Here, we investigate whether the polymorphism is related to altered ins...

  13. Lessons from comparative effectiveness research methods development projects funded under the Recovery Act.

    Science.gov (United States)

    Zurovac, Jelena; Esposito, Dominick

    2014-11-01

    The American Recovery and Reinvestment Act of 2009 (ARRA) directed nearly US$29.2 million to comparative effectiveness research (CER) methods development. To help inform future CER methods investments, we describe the ARRA CER methods projects, identify barriers to this research and discuss the alignment of topics with published methods development priorities. We used several existing resources and held discussions with ARRA CER methods investigators. Although funded projects explored many identified priority topics, investigators noted that much work remains. For example, given the considerable investments in CER data infrastructure, the methods development field can benefit from additional efforts to educate researchers about the availability of new data sources and about how best to apply methods to match their research questions and data.

  14. Structure-activity relationships of the unique and potent agouti-related protein (AGRP)-melanocortin chimeric Tyr-c[beta-Asp-His-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH2 peptide template.

    Science.gov (United States)

    Wilczynski, Andrzej; Wilson, Krista R; Scott, Joseph W; Edison, Arthur S; Haskell-Luevano, Carrie

    2005-04-21

    The melanocortin receptor system consists of endogenous agonists, antagonists, G-protein coupled receptors, and auxiliary proteins that are involved in the regulation of complex physiological functions such as energy and weight homeostasis, feeding behavior, inflammation, sexual function, pigmentation, and exocrine gland function. Herein, we report the structure-activity relationship (SAR) of a new chimeric hAGRP-melanocortin agonist peptide template Tyr-c[beta-Asp-His-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) that was characterized using amino acids previously reported in other melanocortin agonist templates. Twenty peptides were examined in this study, and six peptides were selected for (1)H NMR and computer-assisted molecular modeling structural analysis. The most notable results include the identification that modification of the chimeric template at the His position with Pro and Phe resulted in ligands that were nM mouse melanocortin-3 receptor (mMC3R) antagonists and nM mouse melanocortin-4 receptor (mMC4R) agonists. The peptides Tyr-c[beta-Asp-His-DPhe-Ala-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) and Tyr-c[beta-Asp-His-DNal(1')-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) resulted in 730- and 560-fold, respectively, mMC4R versus mMC3R selective agonists that also possessed nM agonist potency at the mMC1R and mMC5R. Structural studies identified a reverse turn occurring in the His-DPhe-Arg-Trp domain, with subtle differences observed that may account for the differences in melanocortin receptor pharmacology. Specifically, a gamma-turn secondary structure involving the DPhe(4) in the central position of the Tyr-c[beta-Asp-Phe-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) peptide may differentiate the mixed mMC3R antagonist and mMC4R agonist pharmacology.

  15. A Novel β-Globin Chain Hemoglobin Variant, Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp], Associated with Low Oxygen Saturation, Intermittent Aplastic Crises and Splenomegaly.

    Science.gov (United States)

    Collier, Anderson B; Coon, Lea M; Monteleone, Philip; Umaru, Samuel; Swanson, Kenneth C; Hoyer, James D; Oliveira, Jennifer L

    2016-01-01

    Hemoglobin (Hb) variants may be associated with low oxygen saturation and exacerbated episodes of anemia from common stressors such as viral infections. These attributes frequently cause increased clinical concern and unnecessary and expensive testing if not considered early in the evaluation of the patient. Some clinically significant Hb variants result in a normal Hb electrophoresis result, which can be method-dependent. Herein we describe a patient with low oxygen saturation and a history of hemolytic anemia who was subsequently found to carry a novel, unstable β-globin variant that we have named Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp] for the place of identification of the variant. Hb Allentown is formed by a rare double nucleotide substitution within the same codon. Additionally, positive identification of rare Hb variants characterized by a single method is discouraged, as the Hb variant was misclassified as Hb S-South End or β6(A3)Glu→Val;β132(H10)Lys→Asn (HBB: c.[20A > T;399A > C]) by the initial laboratory.

  16. Performance assessment of the PNM Prosperity electricity storage project

    Energy Technology Data Exchange (ETDEWEB)

    Roberson, Dakota [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ellison, James F. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bhatnagar, Dhruv [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Schoenwald, David A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-05-01

    The purpose of this study is to characterize the technical performance of the PNM Prosperity electricity storage project, and to identify lessons learned that can be used to improve similar projects in the future. The PNM Prosperity electricity storage project consists of a 500 kW/350 kWh advanced lead-acid battery with integrated supercapacitor (for energy smoothing) and a 250 kW/1 MWh advanced lead-acid battery (for energy shifting), and is co-located with a 500 kW solar photovoltaic (PV) resource. The project received American Reinvestment and Recovery Act (ARRA) funding. The smoothing system is e ective in smoothing intermittent PV output. The shifting system exhibits good round-trip efficiencies, though the AC-to-AC annual average efficiency is lower than one might hope. Given the current utilization of the smoothing system, there is an opportunity to incorporate additional control algorithms in order to increase the value of the energy storage system.

  17. Plant Line Trial Evaluation of Viable Non-Chromium Passivation Systems for Electrolytin Tinplate, ETP (TRP 9911)

    Energy Technology Data Exchange (ETDEWEB)

    John A. Sinsel

    2003-06-30

    Plant trial evaluations have been completed for two zirconium-based, non-chromium passivation systems previously identified as possible alternatives to cathodic dichromate (CDC) passivation for electrolytic tinplate (ETP). These trials were done on a commercial electrolytic tin plating line at Weirton Steel and extensive evaluations of the materials resulting from these trials have been completed. All this was accomplished as a collaborative effort under the AISI Technology Roadmap Program and was executed by seven North American Tin Mill Products producers [Bethlehem Steel (now acquired by International Steel Group (ISG)), Dofasco Inc., National Steel (now acquired by U.S. Steel), U.S. Steel, USS-Posco, Weirton Steel, and Wheeling-Pittsburgh Steel] with funding partially from the Department of Energy (DOE) and partially on an equal cost sharing basis among project participants. The initial phases of this project involved optimization of application procedures for the non-chromium systems in the laboratories at Bethlehem Steel and Betz Dearborn followed by extensive testing with various lacquer formulations and food simulants in the laboratories at Valspar and PPG. Work was also completed at Dofasco and Weirton Steel to develop methods to prevent precipitation of insoluble solids as a function of time from the zirconate system. The results of this testing indicated that sulfide staining characteristics for the non-chromium passivation systems could be minimized but not totally eliminated and neither system was found to perform quite as good, in this respect, as the standard CDC system. As for the stability of zirconate treatment, a method was developed to stabilize this system for a sufficient period of time to conduct plant trial evaluations but, working with a major supplier of zirconium orthosulfate, a method for long term stabilization is still under development.

  18. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH(2) at the mouse melanocortin receptors. 1. Modifications at the His position.

    Science.gov (United States)

    Holder, Jerry Ryan; Bauzo, Rayna M; Xiang, Zhimin; Haskell-Luevano, Carrie

    2002-06-20

    The melanocortin pathway is an important participant in obesity and energy homeostasis. The centrally located melanocortin-3 and melanocortin-4 receptors (MC3R, MC4R) are involved in the metabolic and food intake aspects of energy homeostasis and are stimulated by melanocortin agonists such as alpha-melanocyte stimulation hormone (alpha-MSH). The melanocortin agonists contain the putative message sequence "His-Phe-Arg-Trp", and it has been well documented that inversion of chirality of the Phe to DPhe results in a dramatic increase in melanocortin receptor potency. Herein, we report a tetrapeptide library based on the template Ac-His-DPhe-Arg-Trp-NH(2), consisting of 17 members that have been modified at the His(6) position (alpha-MSH numbering) and pharmacologically characterized for agonist activity at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R. These studies provide further experimental evidence that the His(6) position can determine MC4R versus MC3R agonist selectivity and that chemically nonreactive side chains may be substituted for the imidazole ring (generally needs to be side chain protected in synthetic schemes) in the design of MC4R-selective, small-molecule, non-peptide agonists. Specifically, the tetrapeptide containing the amino-2-naphthylcarboxylic acid (Anc) amino acid at the His position resulted in a potent agonist at the mMC4R (EC(50) = 21 nM), was a weak mMC3R micromolar antagonist (pA(2) = 5.6, K(i) = 2.5 microM), and possessed >4700-fold agonist selectivity for the MC4R versus the MC3R. Substitution of the His(6) amino acid in the tetrapeptide template by the Phe, Anc, 3-(2-thienyl)alanine (2Thi), and 3-(4-pyridinyl)alanine (4-Pal) resulted in equipotency or only up to a 7-fold decrease in potency, compared to the His(6)-containing tetrapeptide at the mMC4R, demonstrating that these amino acid side chains may be substituted for the imidazole in the design of MC4R-selective non-peptide molecules.

  19. Agonist properties of a stable hexapeptide analog of neurotensin, N alpha MeArg-Lys-Pro-Trp-tLeu-Leu (NT1).

    Science.gov (United States)

    Akunne, H C; Demattos, S B; Whetzel, S Z; Wustrow, D J; Davis, D M; Wise, L D; Cody, W L; Pugsley, T A; Heffner, T G

    1995-04-18

    The major signal transduction pathway for neurotensin (NT) receptors is the G-protein-dependent stimulation of phospholipase C, leading to the mobilization of intracellular free Ca2+ ([Ca2+]i) and the stimulation of cyclic GMP. We investigated the functional actions of an analog of NT(8-13), N alpha MeArg-Lys-Pro-Trp-tLeu-Leu (NT1), and other NT related analogs by quantitative measurement of the cytosolic free Ca2+ concentration in HT-29 (human colonic adenocarcinoma) cells using the Ca(2+)-sensitive dye fura-2/AM and by effects on cyclic GMP levels in rat cerebellar slices. The NT receptor binding affinities for these analogs to HT-29 cell membranes and newborn (10-day-old) mouse brain membranes were also investigated. Data obtained from HT-29 cell and mouse brain membrane preparations showed saturable single high-affinity sites and binding densities (Bmax) of 130.2 and 87.5 fmol/mg protein, respectively. The respective KD values were 0.47 and 0.39 nM, and the Hill coefficients were 0.99 and 0.92. The low-affinity levocabastine-sensitive site was not present (K1 > 10,000) in either membrane preparation. Although the correlation of binding between HT-29 cell membranes and mouse brain membranes was quite significant (r = 0.92), some of the reference agents had lower binding affinities in the HT-29 cell membranes. The metabolically stable compound NT1 plus other NT analogs and related peptides [NT, NT(8-13), xenopsin, neuromedin N, NT(9-13), kinetensin and (D-Trp11)-NT] increased intracellular Ca2+ levels in HT-29 cells, indicating NT receptor agonist properties. The effect of NT1 in mobilizing [Ca2+]i blocked by SR 48692, a non-peptide NT antagonist. Receptor binding affinities of NT analogs to HT-29 cell membranes were positively correlated with potencies for mobilizing intracellular calcium in the same cells. In addition, NT1 increased cyclic GMP levels in rat cerebellar slices, confirming the latter findings of its NT agonist action. These results substantiate

  20. Oral treatment with essential oil of Hyptis spicigera Lam. (Lamiaceae) reduces acute pain and inflammation in mice: Potential interactions with transient receptor potential (TRP) ion channels.

    Science.gov (United States)

    Simões, Róli Rodrigues; Coelho, Igor Dos Santos; Junqueira, Stella Célio; Pigatto, Glauce Regina; Salvador, Marcos José; Santos, Adair Roberto Soares; de Faria, Felipe Meira

    2017-03-22

    The genus Hyptis comprehends almost 400 species widespread in tropical and temperate regions of America. The use of Hyptis spicigera Lam. (Lamiaceae) is reported in traditional medicine due to its gastroprotective, anti-inflammatory and analgesic properties. The rationale of this study was to investigate the potential use of the essential oil of H. spicigera (EOHs) as analgesic. The antinociceptive effect of EOHs was verified analyzing acute nocifensive behavior of mice induced by chemical noxious stimuli [i.e., formalin and transient receptor potential (TRP) channels agonists]. We also verified the effects of EOHs on locomotor activity and motor performance in mice. Finally, we investigate the involvement of central afferent C-fibers with EOHs analgesic effect. EOHs presented antinociceptive effect at 300 and 1000mg/kg on formalin-induced pain behavior model, presenting 50% and 72% of inhibition during the first phase (ED 50 =292mg/kg), and 85% and 100% during de second phase (ED 50 =205mg/kg), respectively. Temperature of the hind paw was reduced by EOHs treatment in a dose-dependent manner; oedema was diminished only by EOHs 1000mg/kg. EOHs does not impaired locomotor activity or motor performance. For mice injected with capsaicin, a TRPV1 activator, EOHs (1000mg/kg, ED 50 =660mg/kg) showed decreased (63%) nociceptive behavior. When injected with cinnamaldehyde (TRPA1 activator), mice treated with EOHs showed 23%, 43% and 66% inhibition on nociceptive behavior (100, 300 and 1000mg/kg, respectively; ED 50 402mg/kg). When mice were injected with menthol (TRPM8 activator), EOHs showed 29%, 59% and 98% inhibition of nociceptive behavior (100, 300 and 1000mg/kg, respectively; with ED 50 =198mg/kg. Finally, when desensitized mice were injected with menthol, EOHs (300mg/kg) does not show antinociceptive effect. This study demonstrated the efficacy of EOHs on experimental models of nociception. We have found the involvement of TRP channels V1, A1 and M8 with EOHs

  1. A novel homozygous Arg222Trp missense mutation in WNT7A in two sisters with severe Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome.

    Science.gov (United States)

    Kantaputra, Piranit N; Mundlos, Stefan; Sripathomsawat, Warissara

    2010-11-01

    Al-Awadi/Raas-Rothschild/Schinzel phocomelia (AARRS) syndrome, a rare autosomal recessive disorder, comprises malformations of upper and lower limbs with severely hypoplastic pelvis and abnormal genitalia. Mutations in WNT7A have been reported as cause of the syndrome. We report on two sisters in a Thai family with short and malformed long bones, absent fibulae, flexion contracture of digits, and a/hypoplastic nails. Fusion between severely malformed femora and slender tibiae has never been reported in patients with WNT7A mutations. Lower limbs were more severely malformed than the upper ones and the pelvis was also severely affected. Multiple fusions of long bones and of the femoral heads to the acetabula were evident. A novel homozygous missense mutation in coding exon 4 of the WNT7A was detected in both affected daughters (c.664C > T) leading to an amino acid exchange from arginine to tryptophan (p.Arg222Trp; R222W). The phenotype is likely to result from an abnormality of all three signaling centers in the developing limb resulting in ventralization with a loss of dorsal structures (aplasia/hypoplasia of nails) a loss of anterior-posterior identity (single distal bones in lower limb without polarity) and an outgrowth defect resulting in distal truncations. © 2010 Wiley-Liss, Inc.

  2. The MECP2 variant c.925C>T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome.

    Science.gov (United States)

    Schönewolf-Greulich, B; Tejada, M-I; Stephens, K; Hadzsiev, K; Gauthier, J; Brøndum-Nielsen, K; Pfundt, R; Ravn, K; Maortua, H; Gener, B; Martínez-Bouzas, C; Piton, A; Rouleau, G; Clayton-Smith, J; Kleefstra, T; Bisgaard, A-M; Tümer, Z

    2016-06-01

    Missense MECP2 variants can have various phenotypic effects ranging from a normal phenotype to typical Rett syndrome (RTT). In females, the phenotype can also be influenced by the X-inactivation pattern. In this study, we present detailed clinical descriptions of six patients with a rare base-pair substitution affecting Arg309 at the C-terminal end of the transcriptional repression domain (TRD). All patients have intellectual disability and present with some RTT features, but they do not fulfill the clinical criteria for typical or atypical RTT. Most of the patients also have mild facial dysmorphism. Intriguingly, the mother of an affected male patient is an asymptomatic carrier of this variant. It is therefore likely that the p.(Arg309Trp) variation does not necessarily lead to male lethality, and it results in a wide range of clinical features in females, probably influenced by different X-inactivation patterns in target tissues. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. p.Ser252Trp and p.Pro253Arg mutations in FGFR2 gene causing Apert syndrome: the first clinical and molecular report of Indonesian patients.

    Science.gov (United States)

    Mundhofir, Farmaditya E P; Sistermans, Erik A; Faradz, Sultana M H; Hamel, Ben C J

    2013-03-01

    Apert syndrome (AS) is a rare autosomal dominant disorder characterised by craniosynostosis and limb malformations, and is associated with congenital heart disease and other systemic malformations, including intellectual disability. We report two Indonesian patients with AS, in whom molecular analysis detected p.Ser252Trp (c.755C>G) and p.Pro253Arg (c.758C>G) mutations in the fibroblast growth factor receptor 2 (FGFR2) gene, respectively. Although the syndrome has been frequently described, this is the first clinical report of AS confirmed by molecular analysis in Indonesia. The difference in severity of clinical features in the two patients may be consistent with a genotype-phenotype correlation of the FGFR2mutation. The management of individuals with AS is best achieved within a multidisciplinary setting. However, in most developing countries, early intervention may be delayed due to late diagnosis, a lack of facilities and financial constraints. This report underpins the benefits of early diagnosis for AS management.

  4. The TRP Channels Pkd2, NompC, and Trpm Act in Cold-Sensing Neurons to Mediate Unique Aversive Behaviors to Noxious Cold in Drosophila.

    Science.gov (United States)

    Turner, Heather N; Armengol, Kevin; Patel, Atit A; Himmel, Nathaniel J; Sullivan, Luis; Iyer, Srividya Chandramouli; Bhattacharya, Surajit; Iyer, Eswar Prasad R; Landry, Christian; Galko, Michael J; Cox, Daniel N

    2016-12-05

    The basic mechanisms underlying noxious cold perception are not well understood. We developed Drosophila assays for noxious cold responses. Larvae respond to near-freezing temperatures via a mutually exclusive set of singular behaviors-in particular, a full-body contraction (CT). Class III (CIII) multidendritic sensory neurons are specifically activated by cold and optogenetic activation of these neurons elicits CT. Blocking synaptic transmission in CIII neurons inhibits CT. Genetically, the transient receptor potential (TRP) channels Trpm, NompC, and Polycystic kidney disease 2 (Pkd2) are expressed in CIII neurons, where each is required for CT. Misexpression of Pkd2 is sufficient to confer cold responsiveness. The optogenetic activation level of multimodal CIII neurons determines behavioral output, and visualization of neuronal activity supports this conclusion. Coactivation of cold- and heat-responsive sensory neurons suggests that the cold-evoked response circuitry is dominant. Our Drosophila model will enable a sophisticated molecular genetic dissection of cold nociceptive genes and circuits. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Project Notes

    Science.gov (United States)

    School Science Review, 1978

    1978-01-01

    Presents sixteen project notes developed by pupils of Chipping Norton School and Bristol Grammar School, in the United Kingdom. These Projects include eight biology A-level projects and eight Chemistry A-level projects. (HM)

  6. Design of a new peptidomimetic agonist for the melanocortin receptors based on the solution structure of the peptide ligand, Ac-Nle-cyclo[Asp-Pro-DPhe-Arg-Trp-Lys]-NH(2).

    Science.gov (United States)

    Fotsch, Christopher; Smith, Duncan M; Adams, Jeffrey A; Cheetham, Janet; Croghan, Michael; Doherty, Elizabeth M; Hale, Clarence; Jarosinski, Mark A; Kelly, Michael G; Norman, Mark H; Tamayo, Nuria A; Xi, Ning; Baumgartner, James W

    2003-07-21

    The solution structure of a potent melanocortin receptor agonist, Ac-Nle-cyclo[Asp-Pro-DPhe-Arg-Trp-Lys]-NH(2) (1) was calculated using distance restraints determined from 1H NMR spectroscopy. Eight of the lowest energy conformations from this study were used to identify non-peptide cores that mimic the spatial arrangement of the critical tripeptide region, DPhe-Arg-Trp, found in 1. From these studies, compound 2a, containing the cis-cyclohexyl core, was identified as a functional agonist of the melanocortin-4 receptor (MC4R) with an IC(50) and EC(50) below 10 nM. Compound 2a also showed 36- and 7-fold selectivity over MC3R and MC1R, respectively, in the binding assays. Subtle changes in cyclohexane stereochemistry and removal of functional groups led to analogues with lower affinity for the MC receptors.

  7. A novel pathogenic variant c.975G>A (p.Trp325*) in the POU3F4 gene in Yakut family (Eastern Siberia, Russia) with the X-linked deafness-2 (DFNX2).

    Science.gov (United States)

    Barashkov, Nikolay A; Klarov, Leonid A; Teryutin, Fedor M; Solovyev, Aisen V; Pshennikova, Vera G; Konnikova, Edilia E; Romanov, Georgii P; Tobokhov, Alexander V; Morozov, Igor V; Bondar, Alexander A; Posukh, Olga L; Dzhemileva, Lilya U; Tomsky, Mikhail I; Khusnutdinova, Elza K; Fedorova, Sardana A

    2018-01-01

    Here, we report a novel hemizygous transition c.975G>A (p.Trp325*) in POU3F4 gene (Xq21) found in two deaf half-brothers from one Yakut family (Eastern Siberia, Russia) with identical inner ear abnormalities ("corkscrew" cochlea with an absence of modiolus) specific to X-linked deafness-2 (DFNX2). Comprehensive clinical evaluation (CT and MR-imaging, audiological and stabilometric examinations) of available members of this family revealed both already known (mixed progressive hearing loss) and additional (enlargement of semicircular canals and postural disorders) clinical DFNX2 features in affected males with c.975G>A (p.Trp325*). Moreover, mild enlargement of semicircular canals, postural abnormalities and different types of hearing thresholds were found in female carrier of this POU3F4-variant. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The Trp64Arg amino acid polymorphism of the beta3-adrenergic receptor gene does not contribute to the genetic susceptibility of diabetic microvascular complications in Caucasian type 1 diabetic patients

    DEFF Research Database (Denmark)

    Tarnow, L; Urhammer, S A; Mottlau, B

    1999-01-01

    OBJECTIVE: The beta3-adrenergic receptor is involved in regulation of microvascular blood flow. A missense mutation (Trp64Arg) in the beta3-adrenergic receptor gene has been suggested as a risk factor for proliferative retinopathy in Japanese type 2 diabetic patients. The aim of the present study...... was to evaluate the contribution of this polymorphism to the development of microangiopathic complications in Caucasian type 1 diabetic patients. SUBJECTS AND METHODS: We studied the relationship between the Trp64Arg polymorphism in type 1 diabetic patients with nephropathy (204 men/132 women, age 42.8 +/- 11.......0 years, diabetes duration 28 +/- 9 years) and in type 1 diabetic patients with persistent normoalbuminuria (118 men/73 women, age 42.6 +/- 10.2 years, diabetes duration 27 +/- 8 years). Proliferative retinopathy was present in 254 patients (48%), while 66 patients (13%) had no diabetic retinopathy...

  9. Genetic variation in the beta 3-adrenoreceptor gene (Trp64Arg polymorphism) and its influence on anthropometric parameters and insulin resistance under a high monounsaturated versus a high polyunsaturated fat hypocaloric diet.

    Science.gov (United States)

    de Luis, D A; Aller, R; Izaola, O; Conde, R; Eiros Bouza, J M

    2013-01-01

    The aim of our study was to investigate the role of Trp64Arg polymorphism of the beta 3-adrenergic receptor (beta 3-AR) gene on metabolic changes and weight loss secondary to a high monounsaturated fat versus a high polyunsaturated fat hypocaloric diet in obese subjects. A population of 260 obese subjects was analyzed. In the basal visit, patients were randomly allocated for 3 months to either diet M (high monounsaturated fat hypocaloric diet) or diet P (high polyunsaturated fat hypocaloric diet). There were no significant differences between the positive effects (on weight, body mass index, waist circumference, fat mass) in either genotype group with both diets. With diet P and in genotype Trp64Trp, glucose levels (-6.7 ± 12.1 vs. -1.2 ± 2.2 mg/dl; p hypocaloric diets is greatest in subjects with the normal homozygous beta 3-AR gene. Improvements in total cholesterol, LDL cholesterol, triglyceride, glucose, insulin and HOMA-R levels were better than in the heterozygous group. Copyright © 2013 S. Karger AG, Basel.

  10. Jiangsu coastal highland reclamation and its wetland ecological construction-a case analysis of the Tiaozini reclamation project

    Science.gov (United States)

    Yu, Meixiu; Xu, Xianghong

    2017-04-01

    Reclamation is one potential solution for the increasing demand of new land for living and development. In past centuries, many coastal countries, such as the Netherlands, UK, Japan, South Korea and Singapore, had exploited extensively sea enclosing and reclamation fordefense against storm surges,agricultural and industrial development, as well as for coastal city expansion along the coast. China has continuously reclaimed coastal sea areas from the 1950s. With rapid economic development and increasing population in coastal areas during recent decades, reclamation has been regarded as an effective measure to resolve the land shortage as cities and industries expand, particularly in South-East coastal areas. Jiangsu province, located in East China, has a similar amount of land territory area to the Netherlands, however, its population is almost fivefold instead. Since its coastal area generates large amounts of tidal flat resources due to its unique hydrodynamic and geomorphic conditions, coastal reclamation plays a vital role in guaranteeing the food security for the Jiangsu Province or even the whole nation. The Tiaozini Reclamation Project (TRP), located between N32.720°-32.882°, E120.894°-120.969°, in Jianggang county of Jiangsu coastal region, with an area of 6,746ha, was reclaimed along the prograding muddy silt coast in 2012. It should be noted that the TRP was reclaimed from theoretical bathymetrical datum of about 4.6m. It is estimated that the shoreline moves towards the sea at a rate of 100m/year and the tidal flat raises at a rate of 5 10 cm/year respectively because of the external tidal flat being continually prograding and drying. After finishing reclamation,the TRP develops with nature: for the dried tidal flat high land,developing ecological agriculture after integrated soil improvement with reducing salt and cultivating fertilizer; for the drying tidal flat,developing ecological fishery by inceasing artificial wetland area; for lower tidal flat

  11. Toxicology and Carcinogenesis Study of Senna in the C3B6.129F1-Trp53tm1Brd N12 haploinsufficient mice

    Science.gov (United States)

    Surh, Inok; Brix, Amy; French, John E.; Collins, Bradley J.; Sanders, J. Michael; Vallant, Molly; Dunnick, June K.

    2013-01-01

    Senna is a pod or leaf of Senna alexandrina P. Mill and is used as a stimulant laxative. In the large intestine, bacterial enzymes break sennosides and release rhein-9-anthrone, the active form for the laxative effect. To determine potential toxic effects of senna, a 5-week dose range finding study in the C57BL/6N mouse and a 40-week toxicology and carcinogenesis study in the C3B6.129F1-Trp53tm1Brd N12 haploinsufficient (p53+/−) mouse were conducted. In the 5-week study, C57BL/6N mice were exposed up to 10,000 ppm senna in feed. Increased incidences of epithelial hyperplasia of the cecum and colon were observed in males and females exposed to 5,000 or 10,000 ppm senna. These intestinal lesions were not considered to be of sufficient severity to cause mortality and, thus, in the p53+/− mouse 40-week study, the high dose of 10,000 ppm was selected. Significant increases in the incidences of epithelial hyperplasia of the colon and cecum were observed at 10,000 ppm in p53(+/−) males and females, and the incidence of hyperplasia of the colon was significantly increased at 3,000 ppm in females. In conclusion, the large intestine was the major target of senna-induced toxicity in both wild-type and the p53+/− mouse model. There was no neoplastic change, when senna was administered to p53 +/− mouse. PMID:23125117

  12. Toxicology and carcinogenesis study of senna in C3B6.129F1-Trp53 tm1Brd N12 haploinsufficient mice.

    Science.gov (United States)

    Surh, Inok; Brix, Amy; French, John E; Collins, Bradley J; Sanders, J Michael; Vallant, Molly; Dunnick, June K

    2013-07-01

    Senna is a pod or leaf of Senna alexandrina P. Mill and is used as a stimulant laxative. In the large intestine, bacterial enzymes reduce sennosides to rhein-9-anthrone, the active form for the laxative effect. To determine the potential toxic effects of senna, a 5-week dose range finding study in the C57BL/6N mouse and a 40-week toxicology and carcinogenesis study in the C3B6.129F1-Trp53 (tm1Brd) N12 haploinsufficient (p53(+/-)) mouse were conducted. In the 5-week study, C57BL/6N mice were exposed to up to 10,000 ppm senna in feed. Increased incidences of epithelial hyperplasia of the cecum and colon were observed in males and females exposed to 5,000 or 10,000 ppm senna. These intestinal lesions were not considered to be of sufficient severity to cause mortality and, thus, in the p53(+/-) mouse 40-week study, the high dose of 10,000 ppm was selected. Significant increases in the incidences of epithelial hyperplasia of the colon and cecum were observed at 10,000 ppm in p53(+/-) males and females, and the incidence of hyperplasia of the colon was significantly increased at 3,000 ppm in females. In conclusion, the large intestine was the major target of senna-induced toxicity in both wild-type and the p53(+/-) mouse model. There was no neoplastic change when senna was administered to p53(+/-) mouse.

  13. Environmental toxin acrolein alters levels of endogenous lipids, including TRP agonists: A potential mechanism for headache driven by TRPA1 activation

    Directory of Open Access Journals (Sweden)

    Emma Leishman

    2017-01-01

    Full Text Available Exposure to airborne toxins can trigger headaches, but the mechanisms are not well understood. Some environmental toxins, such as acrolein, activate transient receptor potential ankyrin 1 (TRPA1, a receptor involved in pain sensation that is highly expressed in the trigeminovascular system. It has been shown in rat models that repeated exposure to acrolein induces trigeminovascular sensitization to both TRPA1 and TRP vanilloid 1 (TRPV1 agonists, a phenomenon linked to headache. In this study, we test the hypothesis that the sensitization of trigeminovascular responses in rats after acrolein exposure via inhalation is associated with changes in levels of endogenous lipids, including TRPV1 agonists, in the trigeminal ganglia, trigeminal nucleus, and cerebellum. Lipidomics analysis of 80 lipids was performed on each tissue after acute acrolein, chronic acrolein, or room air control. Both acute and chronic acrolein exposure drove widespread alterations in lipid levels. After chronic acrolein exposure, levels of all 6 N-acyl ethanolamines in the screening library, including the endogenous cannabinoid and TRPV1 agonist, N-arachidonoyl ethanolamine, were elevated in trigeminal tissue and in the cerebellum. This increase in TRPV1 ligands by acrolein exposure may indicate further downstream signaling, in that we also show here that a combination of these TRPV1 endogenous agonists increases the potency of the individual ligands in TRPV1-HEK cells. In addition to these TRPV1 agonists, 3 TRPV3 antagonists, 4 TRPV4 agonists, and 25 orphan lipids were up and down regulated after acrolein exposure. These data support the hypothesis that lipid signaling may represent a mechanism by which repeated exposure to the TRPA1 agonist and environmental toxin, acrolein, drives trigeminovascular sensitization. Keywords: Lipidomics, Endogenous cannabinoid, TRPA1, TRPV1, Lipoamine, Acrolein, Migraine

  14. RELACIÓN ENTRE LOS NIVELES DE TRP'S, LAS MEDIDAS DE RECORDACIÓN, PREFERENCIA DE MARCA Y LA CONDUCTA DE COMPRA EN CONSUMIDORES COLOMBIANOS

    Directory of Open Access Journals (Sweden)

    Diana María López Celis

    2010-01-01

    Full Text Available El propósito de la investigación es determinar las relaciones existentes entre los niveles de Target Rating Point (TRP´S entendidos como el índice acumulado de rating de Televisión mensual frente a los niveles de notoriedad (conocimiento de marca y publicitario, preferencia (favoritismo y comportamiento (compra y próxima compra, a fin de identificar las principales tendencias derivadas de dichas asociaciones en una categoría de consumo masivo. Para esto, se tomaron los niveles de TRP´S en Televisión, como variable predictora central, así como las medidas de notoriedad de marca (top of mind, espontánea y ayudada, las medidas de notoriedad publicitaria (top of mind, espontánea y ayudada, las medidas de preferencia (marca favorita y las variables de compra (marca comprada en el último mes y próxima marca a comprar clasificadas en el conjunto de las variables criterio. El diseño de este estudio es de corte longitudinal de tendencia con K muestras, la muestra general del estudio comprende un conjunto de 4.104 registros agregados derivados de la replicación de 58 muestras mensuales de 500 participantes de ambos géneros con edades entre los 12 y 60 años pertenecientes a los estratos 2 al 6 dentro del período comprendido entre enero de 2004 y octubre de 2008. Los principales hallazgos resaltan el establecimiento de asociaciones estadísticamente significativas entre los niveles de TRP'S (bajo-medio y alto y el comportamiento diferencial de cada una de las 3 marcas evaluadas dentro de la categoría en relación con sus niveles de notoriedad, preferencia y compra.

  15. FY2011 Annual Report for NREL Energy Storage Projects

    Energy Technology Data Exchange (ETDEWEB)

    Pesaran, A.; Ban, C.; Dillon, A.; Gonder, J.; Ireland, J.; Keyser, M.; Kim, G. H.; Lee, K. J.; Long, D.; Neubauer, J.; Santhangopalan, S.; Smith, K.

    2012-04-01

    This report describes the work of NREL's Energy Storage group for FY2011. The National Renewable Energy Laboratory (NREL) supports energy storage R&D under the Vehicle Technologies Program at the U.S. Department of Energy (DOE). The DOE Energy Storage program's charter is to develop battery technologies that will enable large market penetration of electric drive vehicles. These vehicles could have a significant impact on the nation's goal of reducing dependence on imported oil and gaseous pollutant emissions. DOE has established several program activities to address and overcome the barriers limiting the penetration of electric drive battery technologies: cost, performance, safety, and life. These programs are: (1) Advanced Battery Development [through the United States Advanced Battery Consortium (USABC)]; (2) Testing, Design and Analysis (TDA); (3) Applied Battery Research (ABR); and (4) Focused Fundamental Research, or Batteries for Advanced Transportation Technologies (BATT). In FY11, DOE funded NREL to make technical contributions to all of these R&D activities. This report summarizes NREL's R&D projects in FY11 in support of the USABC, TDA, ABR, and BATT program elements. In addition, we continued the enhancement of NREL's battery testing facilities funded through the American Reinvestment and Recovery Act (ARRA) of 2009. The FY11 projects under NREL's Energy Storage R&D program are briefly described below. Each of these is discussed in depth in the main sections of this report.

  16. El Paso County Geothermal Project at Fort Bliss. Final Project Report

    Energy Technology Data Exchange (ETDEWEB)

    Lear, Jon [Ruby Mountain Inc., Salt Lake City, UT (United State); Bennett, Carlon [Ruby Mountain Inc., Salt Lake City, UT (United State); Lear, Dan [Ruby Mountain Inc., Salt Lake City, UT (United State); Jones, Phil L. [Ruby Mountain Inc., Salt Lake City, UT (United State); Burdge, Mark [Evergreen Clean Energy Management, Provo, UT (United States); Barker, Ben [Evergreen Clean Energy Management, Provo, UT (United States); Segall, Marylin [Univ. of Utah, Salt Lake City, UT (United States). Energy and Geoscience Inst.; Moore, Joseph [Univ. of Utah, Salt Lake City, UT (United States). Energy and Geoscience Inst.; Nash, Gregory [Univ. of Utah, Salt Lake City, UT (United States). Energy and Geoscience Inst.; Jones, Clay [Univ. of Utah, Salt Lake City, UT (United States). Energy and Geoscience Inst.; Simmons, Stuart [Univ. of Utah, Salt Lake City, UT (United States). Energy and Geoscience Inst.; Taylor, Nancy [Univ. of Utah, Salt Lake City, UT (United States). Energy and Geoscience Inst.

    2016-02-01

    The El Paso County Geothermal Project at Fort Bliss was an effort to determine the scale and scope of geothermal resources previously identified on Fort Bliss’ McGregor Range in southern Otero County, New Mexico. The project was funded with a $5,000,000 grant to El Paso County from the U.S. Department of Energy (DOE) as part of the American Recovery and Reinvestment Act of 2009 and a $4,812,500 match provided by private sector partners. The project was administered through the DOE Golden Field Office to awardee El Paso County. The primary subcontractor to El Paso County and project Principal Investigator - Ruby Mountain Inc. (RMI) of Salt Lake City, Utah - assembled the project team consisting of Evergreen Clean Energy Management (ECEM) of Provo, Utah, and the Energy & Geoscience Institute at the University of Utah (EGI) in Salt Lake City, UT to complete the final phases of the project. The project formally began in May of 2010 and consisted of two preliminary phases of data collection and evaluation which culminated in the identification of a drilling site for a Resource Confirmation Well on McGregor Range. Well RMI 56-5 was drilled May and June 2013 to a depth of 3,030 ft. below ground level. A string of slotted 7 inch casing was set in 8.75 inch hole on bottom fill at 3,017 ft. to complete the well. The well was drilled using a technique called flooded reverse circulation, which is most common in mineral exploration. This technique produced an exceptionally large and complete cuttings record. An exciting development at the conclusion of drilling was the suspected discovery of a formation that has proven to be of exceptionally high permeability in three desalinization wells six miles to the south. Following drilling and preliminary testing and analysis, the project team has determined that the McGregor Range thermal anomaly is large and can probably support development in the tens of megawatts.

  17. Define Project

    DEFF Research Database (Denmark)

    Munk-Madsen, Andreas

    2005-01-01

    "Project" is a key concept in IS management. The word is frequently used in textbooks and standards. Yet we seldom find a precise definition of the concept. This paper discusses how to define the concept of a project. The proposed definition covers both heavily formalized projects and informally...... organized, agile projects. Based on the proposed definition popular existing definitions are discussed....

  18. Project Management

    DEFF Research Database (Denmark)

    Project Management Theory Meets Practice contains the proceedings from the 1st Danish Project Management Research Conference (DAPMARC 2015), held in Copenhagen, Denmark, on May 21st, 2015.......Project Management Theory Meets Practice contains the proceedings from the 1st Danish Project Management Research Conference (DAPMARC 2015), held in Copenhagen, Denmark, on May 21st, 2015....

  19. Project Management

    DEFF Research Database (Denmark)

    Pilkington, Alan; Chai, Kah-Hin; Le, Yang

    2015-01-01

    This paper identifies the true coverage of PM theory through a bibliometric analysis of the International Journal of Project Management from 1996-2012. We identify six persistent research themes: project time management, project risk management, programme management, large-scale project management......, project success/failure and practitioner development. These differ from those presented in review and editorial articles in the literature. In addition, topics missing from the PM BOK: knowledge management project-based organization and project portfolio management have become more popular topics...

  20. Project financing

    International Nuclear Information System (INIS)

    Cowan, A.

    1998-01-01

    Project financing was defined ('where a lender to a specific project has recourse only to the cash flow and assets of that project for repayment and security respectively') and its attributes were described. Project financing was said to be particularly well suited to power, pipeline, mining, telecommunications, petro-chemicals, road construction, and oil and gas projects, i.e. large infrastructure projects that are difficult to fund on-balance sheet, where the risk profile of a project does not fit the corporation's risk appetite, or where higher leverage is required. Sources of project financing were identified. The need to analyze and mitigate risks, and being aware that lenders always take a conservative view and gravitate towards the lowest common denominator, were considered the key to success in obtaining project financing funds. TransAlta Corporation's project financing experiences were used to illustrate the potential of this source of financing

  1. Project descriptions

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    This part specifies the activities and project tasks of each project broken down according to types of financing, listing the current projects Lw 1 through 3 funded by long-term provisions (budget), the current projects LB 1 and 2, LG 1 through 5, LK1, LM1, and LU 1 through 6 financed from special funds, and the planned projects ZG 1 through 4 and ZU 1, also financed from special funds. (DG) [de

  2. N-terminal fatty acylated His-dPhe-Arg-Trp-NH(2) tetrapeptides: influence of fatty acid chain length on potency and selectivity at the mouse melanocortin receptors and human melanocytes.

    Science.gov (United States)

    Todorovic, Aleksandar; Holder, Jerry Ryan; Bauzo, Rayna M; Scott, Joseph Walker; Kavanagh, Renny; Abdel-Malek, Zalfa; Haskell-Luevano, Carrie

    2005-05-05

    The melanocortin system is involved in the regulation of a diverse number of physiologically important pathways including pigmentation, feeding behavior, weight and energy homeostasis, inflammation, and sexual function. All the endogenous melanocortin agonist ligands possess the conserved His-Phe-Arg-Trp tetrapeptide sequence that is postulated to be important for melanocortin receptor molecular recognition and stimulation. Previous studies by our laboratory resulted in the discovery that increasing alkyl chain length at the N-terminal "capping" region of the His-dPhe-Arg-Trp-NH(2) tetrapeptide resulted in a 100-fold increased melanocortin receptor agonist potency. This study was undertaken to systematically evaluate the pharmacological effects of increasing N-capping alkyl chain length of the CH(3)(CH(2))(n)CO-His-dPhe-Arg-Trp-NH(2) (n = 6-16) tetrapeptide template. Twelve analogues were synthesized and pharmacologically characterized at the mouse melanocortin receptors MC1R and MC3R-MC5R and human melanocytes known to express the MC1R. These peptides demonstrated melanocortin receptor selectivity profiles different from those of previously published tetrapeptides. The most notable results of enhanced ligand potency (20- to 200-fold) and receptor selectivity were observed at the MC1R. Tetrapeptides that possessed greater than nine alkyl groups were superior to alpha-MSH in terms of the stimulation of human melanocyte tyrosinase activity. Additionally, the n-pentadecanoyl derivative had a residual effect on tyrosinase activity that existed for at least 4 days after the peptide was removed from the human melanocyte culture medium. These data demonstrate the utility, potency, and residual effect of melanocortin tetrapeptides by adding N-terminal fatty acid moieties.

  3. Copper-induced activation of TRP channels promotes extracellular calcium entry and activation of CaMs and CDPKs leading to copper entry and membrane depolarization in Ulva compressa

    Directory of Open Access Journals (Sweden)

    Melissa eGómez

    2015-03-01

    Full Text Available In order to identify channels involved in membrane depolarization, Ulva compressa was incubated with agonists of TRP channels C5, A1 and V1 and the level of intracellular calcium was detected. Agonists of TRPC5, A1 and V1 induced increases in intracellular calcium at 4, 9 and 12 min of exposure, respectively, and antagonists of TRPC5, A1 and V1 corresponding to SKF-96365 (SKF, HC-030031 (HC and capsazepin (CPZ, respectively, inhibited calcium increases indicating that functional TRPs exist in U. compressa. In addition, copper excess induced increases in intracellular calcium at 4, 9 and 12 min which were inhibited by SKF, HC and CPZ, respectively, indicating that copper activate TRPC5, A1 and V1 channels. Moreover, copper-induced calcium increases were inhibited by EGTA, a non-permeable calcium chelating agent, but not by thapsigargin, an inhibitor of endoplasmic reticulum (ER calcium ATPase, indicating that activation of TRPs leads to extracellular calcium entry. Furthermore, copper-induced calcium increases were not inhibited by W-7, an inhibitor of CaMs, and staurosporine, an inhibitor of CDPKs, indicating that extracellular calcium entry did not require CaMs and CDPKs activation. In addition, copper induced membrane depolarization events at 4, 8 and 11 min and these events were inhibited by SKF, HC, CPZ and bathocuproine, a specific copper chelating agent, indicating copper entry through TRP channels leading to membrane depolarization. Moreover, membrane depolarization events were inhibited by W-7 and staurosporine, indicating that CaMs and CDPKs are required in order to activate TRPs to allow copper entry. Thus, light-dependent copper-induced activation TRPC5, A1 and V1 promotes extracellular calcium entry leading to activation of CaMs and CDPKs which, in turn, promotes copper entry through these TRP channels leading to membrane depolarization.

  4. Obesity is associated with the Arg389Gly ADRB1 but not with the Trp64Arg ADRB3 polymorphism in children from San Luis PotosÍ and León, México.

    Science.gov (United States)

    Aradillas-Garc X Cd, Celia; Cruz, Miguel; Pérez-Luque, Elva; Garay-Sevilla, María E; Malacara, Juan M; R, Aduna; Peralta, Jesús; Burguete-García, Ana; Alegría-Torres, Jorge A

    2016-10-17

    This research was designed to analyze the possible associations of Arg389Gly ADRB1 and Trp64Arg ADRB3 polymorphisms in children with obesity. A cross-sectional study included 1,046 school-age Mexican participants (6-12 years old) from the cities of San Luis PotosÍ and León. Children were classified as non-obese or obese according to their body mass index (BMI) percentile; obese children had a BMI≥95th percentile for sex and age. Biochemical data were collected. Polymorphisms were detected using TaqMan qPCR assay. A logistic regression analysis was used to calculate the risk of obesity based on genotypes. Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure, fasting plasma glucose, insulin, HOMA-IR, LDL-cholesterol, triglycerides, and lower HDL-cholesterol compared with the normal weight group (P<0.05). The distribution of allele frequency in the population was Arg= 87.4 and Gly= 12.6 (Hardy Weinberg equilibrium c 2 = 3.16 , P = 0.07 ); Trp= 81.5 and Arg= 18.5 (Hardy Weinberg equilibrium c 2 = 2.2, P = 0.14 ) for ADRB1 and ADRB3, respectively. Even though no different frequencies of Arg389Gly polymorphism between groups were found (P = 0.08), children carriers of one Gly389 ADRB1 allele had a risk for obesity of OR=1.40 (95%CI, 1.03-1.90, P = 0.03) after adjustment for age and gender. No other association was found for Trp64Arg ADRB3 polymorphism. Only the Arg389Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.

  5. DNA Repair Mechanism Gene, XRCC1A (Arg194Trp) but not XRCC3 (Thr241Met) Polymorphism Increased the Risk of Breast Cancer in Premenopausal Females: A Case–Control Study in Northeastern Region of India

    Science.gov (United States)

    Ahmed, Jishan; Narain, Kanwar; Mukherjee, Kaustab; Majumdar, Gautam; Chenkual, Saia; Zonunmawia, Jason C.

    2017-01-01

    X-ray repair cross complementary group gene is one of the most studied candidate gene involved in different types of cancers. Studies have shown that X-ray repair cross complementary genes are significantly associated with increased risk of breast cancer in females. Moreover, studies have revealed that X-ray repair cross complementary gene polymorphism significantly varies between and within different ethnic groups globally. The present case–control study was aimed to investigate the association of X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross complementary 3 (Thr241Met) polymorphism with the risk of breast cancer in females from northeastern region of India. The present case–control study includes histopathologically confirmed and newly diagnosed 464 cases with breast cancer and 534 apparently healthy neighborhood community controls. Information on sociodemographic factors and putative risk factors were collected from each study participant by conducting face-to-face interviews. Genotyping of X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross complementary 3 (Thr241Met) was carried out by polymerase chain reaction-restriction fragment length polymorphism. For statistical analysis, both univariate and multivariate logistic regression analyses were performed. We also performed stratified analysis to find out the association of X-ray repair cross complementary genes with the risk of breast cancer stratified based on menstrual status. This study revealed that tryptophan allele (R/W-W/W genotype) in X-ray repair cross complementary 1A (Arg194Trp) gene significantly increased the risk of breast cancer (adjusted odds ratio = 1.44, 95% confidence interval = 1.06-1.97, P India which may be beneficial for prognostic purposes. PMID:29332455

  6. Cross-resistance patterns to acetolactate synthase (ALS)-inhibiting herbicides of flixweed (Descurainia sophia L.) conferred by different combinations of ALS isozymes with a Pro-197-Thr mutation or a novel Trp-574-Leu mutation.

    Science.gov (United States)

    Deng, Wei; Yang, Qian; Zhang, Yongzhi; Jiao, Hongtao; Mei, Yu; Li, Xuefeng; Zheng, Mingqi

    2017-03-01

    Acetolactate synthase (ALS) is the common target of ALS-inhibiting herbicides, and target-site ALS mutations are the main mechanism of resistance to ALS-inhibiting herbicides. In this study, ALS1 and ALS2 genes with full lengths of 2004bp and 1998bp respectively were cloned in individual plants of susceptible (S) or resistant (R) flixweed (Descurainia sophia L.) populations. Two ALS mutations of Pro-197-Thr and/or Trp-574-Leu were identified in plants of three R biotypes (HB24, HB30 and HB42). In order to investigate the function of ALS isozymes in ALS-inhibiting herbicide resistance, pHB24 (a Pro-197-Thr mutation in ALS1 and a wild type ALS2), pHB42 (a Trp-574-Leu mutation in ALS1 and a wild type ALS2) and pHB30 (a Trp-574-Leu mutation in ALS1 and a Pro-197-Thr mutation in ALS2) subpopulations individually homozygous for different ALS mutations were generated. Individuals of pHB30 had mutations in each isozyme of ALS and had higher resistance than pHB24 and pHB42 populations containing mutations in only one ALS isozyme. Moreover, the pHB24 had resistance to SU, TP and SCT herbicides, whereas pHB24 and pHB42 had resistance to these classes of herbicides as well as IMI and PTB herbicides. The sensitivity of isolated ALS enzyme to inhibition by herbicides in these populations correlated with whole plant resistance levels. Therefore, reduced ALS sensitivity resulting from the mutations in ALS was responsible for resistance to ALS-inhibiting herbicides in flixweed. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. In vitro effects of substance P analogue [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P on human tumour and normal cell growth.

    OpenAIRE

    Everard, M. J.; Macaulay, V. M.; Miller, J. L.; Smith, I. E.

    1992-01-01

    Analogues of the neurotransmitter substance P (SP) can interact with neuropeptide receptors, and are reported to inhibit growth of small cell lung cancer cell lines (SCLC CLs). We found [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P (D-Phe5SP) significantly inhibited DNA synthesis by 10/10 human tumour CLs; six SCLC, one N-SCLC (squamous), two ovarian and one squamous cervical carcinoma, with inhibition to 50% control levels (IC50) of 20-50 microM. There was dose dependent inhibition of colony...

  8. Melanocortin Tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 Modified at the Para Position of the Benzyl Side Chain (DPhe): Importance for Mouse Melanocortin-3 Receptor Agonist versus Antagonist Activity

    OpenAIRE

    Proneth, Bettina; Pogozheva, Irina D.; Portillo, Federico P.; Mosberg, Henry I.; Haskell-Luevano, Carrie

    2008-01-01

    The melanocortin-3 and -4 receptors (MC3R, MC4R) have been implicated in energy homeostasis and obesity. Whereas the physiological role of the MC4R is extensively studied, little is known about the MC3R. One caveat is the limited availability of ligands that are selective for the MC3R. Previous studies identified Ac-His-DPhe(p-I)-Arg-Trp-NH2, which possessed partial agonist/antagonist pharmacology at the mMC3R while retaining full nanomolar agonist pharmacology at the mMC4R. These data allowe...

  9. Project studies

    DEFF Research Database (Denmark)

    Geraldi, Joana; Söderlund, Jonas

    2018-01-01

    Project organising is a growing field of scholarly inquiry and management practice. In recent years, two important developments have influenced this field: (1) the study and practice of projects have extended their level of analysis from mainly focussing on individual projects to focussing on micro......, and of the explanations of project practices they could offer. To discuss avenues for future research on projects and project practice, this paper suggests the notion of project studies to better grasp the status of our field. We combine these two sets of ideas to analyse the status and future options for advancing...... project research: (1) levels of analysis; and (2) type of research. Analysing recent developments within project studies, we observe the emergence of what we refer to as type 3 research, which reconciles the need for theoretical development and engagement with practice. Type 3 research suggests pragmatic...

  10. Virtual projects

    DEFF Research Database (Denmark)

    Svejvig, Per; Commisso, Trine Hald

    2012-01-01

    that the best practice knowledge has not permeated sufficiently to the practice. Furthermore, the appropriate application of information and communication technology (ICT) remains a big challenge, and finally project managers are not sufficiently trained in organizing and conducting virtual projects....... The overall implications for research and practice are to acknowledge virtual project management as very different to traditional project management and to address this difference.......Virtual projects are common with global competition, market development, and not least the financial crisis forcing organizations to reduce their costs drastically. Organizations therefore have to place high importance on ways to carry out virtual projects and consider appropriate practices...

  11. Project financing

    International Nuclear Information System (INIS)

    Alvarez, M.U.

    1990-01-01

    This paper presents the basic concepts and components of the project financing of large industrial facilities. Diagrams of a simple partnership structure and a simple leveraged lease structure are included. Finally, a Hypothetical Project is described with basic issues identified for discussion purposes. The topics of the paper include non-recourse financing, principal advantages and objectives, disadvantages, project financing participants and agreements, feasibility studies, organization of the project company, principal agreements in a project financing, insurance, and an examination of a hypothetical project

  12. Microsoft project

    OpenAIRE

    Markić, Lucija; Mandušić, Dubravka; Grbavac, Vitomir

    2005-01-01

    Microsoft Project je alat čije su prednosti u svakodnevnom radu nezamjenjive. Pomoću Microsoft Projecta omogućeno je upravljanje resursima, stvaranje izvještaja o projektima u vremenu, te analize različitih scenarija. Pojavljuje u tri verzije: Microsoft Project Professional, Microsoft Project Server i Microsoft Project Server Client Access Licenses. Upravo je trend da suvremeni poslovni ljudi zadatke povjeravaju Microsoft Projectu jer on znatno povećava produktivnost rada. Te prednos...

  13. Project ethics

    CERN Document Server

    Jonasson, Haukur Ingi

    2013-01-01

    How relevant is ethics to project management? The book - which aims to demystify the field of ethics for project managers and managers in general - takes both a critical and a practical look at project management in terms of success criteria, and ethical opportunities and risks. The goal is to help the reader to use ethical theory to further identify opportunities and risks within their projects and thereby to advance more directly along the path of mature and sustainable managerial practice.

  14. Trp[superscript 2313]-His[superscript 2315] of Factor VIII C2 Domain Is Involved in Membrane Binding Structure of a Complex Between the C[subscript 2] Domain and an Inhibitor of Membrane Binding

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhuo; Lin, Lin; Yuan, Cai; Nicolaes, Gerry A.F.; Chen, Liqing; Meehan, Edward J.; Furie, Bruce; Furie, Barbara; Huang, Mingdong (Harvard-Med); (UAH); (Maastricht); (Chinese Aca. Sci.)

    2010-11-03

    Factor VIII (FVIII) plays a critical role in blood coagulation by forming the tenase complex with factor IXa and calcium ions on a membrane surface containing negatively charged phospholipids. The tenase complex activates factor X during blood coagulation. The carboxyl-terminal C2 domain of FVIII is the main membrane-binding and von Willebrand factor-binding region of the protein. Mutations of FVIII cause hemophilia A, whereas elevation of FVIII activity is a risk factor for thromboembolic diseases. The C2 domain-membrane interaction has been proposed as a target of intervention for regulation of blood coagulation. A number of molecules that interrupt FVIII or factor V (FV) binding to cell membranes have been identified through high throughput screening or structure-based design. We report crystal structures of the FVIII C2 domain under three new crystallization conditions, and a high resolution (1.15 {angstrom}) crystal structure of the FVIII C2 domain bound to a small molecular inhibitor. The latter structure shows that the inhibitor binds to the surface of an exposed {beta}-strand of the C2 domain, Trp{sup 2313}-His{sup 2315}. This result indicates that the Trp{sup 2313}-His{sup 2315} segment is an important constituent of the membrane-binding motif and provides a model to understand the molecular mechanism of the C2 domain membrane interaction.

  15. Modification by preirradiation growth conditions of the shoulder of the UV fluence-survival curve of Escherichia coli B/r WP2 thy trp and changes in mutagenic response toward tryptophan prototrophy

    International Nuclear Information System (INIS)

    Doudney, C.O.

    1978-01-01

    The distinct three-section UV fluence-mutation frequency response (MFR) curve demonstrated in Escherichia coli strain B/r WP2 thy trp and its uvrA derivative supports the SOS hypothesis and suggests that trp + revertants can arise either from isolated lesions (1DM) plus SOS induction or from two lesions in proximity (2DM). Preirradiation growth on arabinose instead of glucose converted the fluence-survival curve from highly shouldered to exponential but did not affect the three-section MFR curve. Prestarvation of the uvrA + strain for typtophan, which drastically increases the expanse of the shoulder of the survival curve, greatly decreased both 1DM and 2DM. With the uvrA strain the increase in shoulder expanse after typtophan prestarvation was accompanied by greatly increased 2DM but no change in 1DM. Preincubation with chloramphenicol induced an even greater increase in 2DM response than amino acid prestarvation. Nalidixic acid, which prevents DNA accumulation, eliminated the response. (Auth.)

  16. The growth hormone (GH) response to GH-releasing peptide (His-DTrp-Ala-Trp-DPhe-Lys-NH2), GH-releasing hormone, and thyrotropin-releasing hormone in acromegaly.

    Science.gov (United States)

    Alster, D K; Bowers, C Y; Jaffe, C A; Ho, P J; Barkan, A L

    1993-09-01

    In patients with acromegaly, GH-producing pituitary tumors release GH in response to specific stimuli such as GH-releasing hormone (GHRH) and are also responsive to a variety of nonspecific stimuli, such as TRH or GnRH, and may exhibit paradoxical responses to glucose and dopamine. In healthy humans, the synthetic peptide GH-releasing peptide (GHRP) (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) releases GH by a putative mechanism of action that is independent of GHRH. How these tumors respond to GHRP is not well characterized. We studied the GH responses to GHRH, GHRP, and TRH stimulation in 11 patients with active acromegaly. The peak GH responses to GHRP and GHRH were not correlated (r = 0.57; P = 0.066). In contrast, the peak GH responses to GHRP and TRH were highly correlated (r = 0.95; P < 0.001). In conclusion, in patients with acromegaly, the GH response to GHRP is qualitatively normal and does not appear to depend on GHRH.

  17. Melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 modified at the para position of the benzyl side chain (DPhe): importance for mouse melanocortin-3 receptor agonist versus antagonist activity.

    Science.gov (United States)

    Proneth, Bettina; Pogozheva, Irina D; Portillo, Federico P; Mosberg, Henry I; Haskell-Luevano, Carrie

    2008-09-25

    The melanocortin-3 and -4 receptors (MC3R, MC4R) have been implicated in energy homeostasis and obesity. Whereas the physiological role of the MC4R is extensively studied, little is known about the MC3R. One caveat is the limited availability of ligands that are selective for the MC3R. Previous studies identified Ac-His-DPhe(p-I)-Arg-Trp-NH 2, which possessed partial agonist/antagonist pharmacology at the mMC3R while retaining full nanomolar agonist pharmacology at the mMC4R. These data allowed for the hypothesis that the DPhe position in melanocortin tetrapeptides can be used to examine ligand side-chain determinants important for differentiation of mMC3R agonist versus antagonist activity. A series of 15 DPhe (7) modified Ac-His-DPhe (7)-Arg-Trp-NH 2 tetrapeptides has been synthesized and pharmacologically characterized. Most notable results include the identification of modifications that resulted in potent antagonists/partial agonists at the mMC3R and full, potent agonists at the mMC4R. These SAR studies provide experimental evidence that the molecular mechanism of antagonism at the mMC3R differentiates this subtype from the mMC4R.

  18. Towards understanding the tandem mass spectra of protonated oligopeptides. 2: The proline effect in collision-induced dissociation of protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp).

    Science.gov (United States)

    Bleiholder, Christian; Suhai, Sándor; Harrison, Alex G; Paizs, Béla

    2011-06-01

    The product ion spectra of proline-containing peptides are commonly dominated by y(n) ions generated by cleavage at the N-terminal side of proline residues. This proline effect is investigated in the current work by collision-induced dissociation (CID) of protonated Ala-Ala-Xxx-Pro-Ala (Xxx includes Ala, Ser, Leu, Val, Phe, and Trp) in an electrospray/quadrupole/time-of-flight (QqTOF) mass spectrometer and by quantum chemical calculations on protonated Ala-Ala-Ala-Pro-Ala. The CID spectra of all investigated peptides show a dominant y(2) ion (Pro-Ala sequence). Our computational results show that the proline effect mainly arises from the particularly low threshold energy for the amide bond cleavage N-terminal to the proline residue, and from the high proton affinity of the proline-containing C-terminal fragment produced by this cleavage. These theoretical results are qualitatively supported by the experimentally observed y(2)/b(3) abundance ratios for protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp). In the post-cleavage phase of fragmentation the N-terminal oxazolone fragment with the Ala-Ala-Xxx sequence and Pro-Ala compete for the ionizing proton for these peptides. As the proton affinity of the oxazolone fragment increases, the y(2)/b(3) abundance ratio decreases.

  19. Project Temporalities

    DEFF Research Database (Denmark)

    Tryggestad, Kjell; Justesen, Lise; Mouritsen, Jan

    2013-01-01

    Purpose – The purpose of this paper is to explore how animals can become stakeholders in interaction with project management technologies and what happens with project temporalities when new and surprising stakeholders become part of a project and a recognized matter of concern to be taken...... into account. Design/methodology/approach – The paper is based on a qualitative case study of a project in the building industry. The authors use actor-network theory (ANT) to analyze the emergence of animal stakeholders, stakes and temporalities. Findings – The study shows how project temporalities can...... multiply in interaction with project management technologies and how conventional linear conceptions of project time may be contested with the emergence of new non-human stakeholders and temporalities. Research limitations/implications – The study draws on ANT to show how animals can become stakeholders...

  20. Office of Electricity Delivery and Energy Reliability (OE) National Energy Technology Laboratory (NETL) American Recovery and Reinvestment Act 2009 United States Department of Energy

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Mohit [Seeo, Incorporated, Hayward, CA (United States); Grape, Ulrik [Seeo, Incorporated, Hayward, CA (United States)

    2014-07-29

    The purpose of this project was for Seeo to deliver the first ever large-scale or grid-scale prototype of a new class of advanced lithium-ion rechargeable batteries. The technology combines unprecedented energy density, lifetime, safety, and cost. The goal was to demonstrate Seeo’s entirely new class of lithium-based batteries based on Seeo’s proprietary nanostructured polymer electrolyte. This technology can enable the widespread deployment in Smart Grid applications and was demonstrated through the development and testing of a 10 kilowatt-hour (kWh) prototype battery system. This development effort, supported by the United States Department of Energy (DOE) enabled Seeo to pursue and validate the transformational performance advantages of its technology for use in grid-tied energy storage applications. The focus of this project and Seeo’s goal as demonstrated through the efforts made under this project is to address the utility market needs for energy storage systems applications, especially for residential and commercial customers tied to solar photovoltaic installations. In addition to grid energy storage opportunities Seeo’s technology has been tested with automotive drive cycles and is seen as equally applicable for battery packs for electric vehicles. The goals of the project were outlined and achieved through a series of specific tasks, which encompassed materials development, scaling up of cells, demonstrating the performance of the cells, designing, building and demonstrating a pack prototype, and providing an economic and environmental assessment. Nearly all of the tasks were achieved over the duration of the program, with only the full demonstration of the battery system and a complete economic and environmental analysis not able to be fully completed. A timeline over the duration of the program is shown in figure 1.

  1. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P, a potent bombesin antagonist in murine Swiss 3T3 cells, inhibits the growth of human small cell lung cancer cells in vitro.

    OpenAIRE

    Woll, P J; Rozengurt, E

    1988-01-01

    In the search for a more potent bombesin antagonist, we found [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P to be effective in mouse fibroblasts and to inhibit the growth of small cell lung cancer, a tumor that secretes bombesin-like peptides that may act as autocrine growth factors. In murine Swiss 3T3 cells, [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P proved to be a bombesin antagonist as judged by the following criteria: (i) inhibition of DNA synthesis induced by gastrin-releasing peptide and ot...

  2. American Recovery and Reinvestment Act (ARRA) FEMP Technical Assistance U.S. Army – Project 214 Analysis of Regulations Associated with Implementation of a Rocky Mountain Secure Smart-Grid

    Energy Technology Data Exchange (ETDEWEB)

    Warwick, William M.

    2010-09-30

    This document describes technical assistance provided by PNNL to further develop a smart grid technologies concept to provide a basis for policies and plans for the US Army. The effort was to analyze the potential to utilize emerging smart grid technologies along with indigenous renewable and other resources to meet the emergency and other power needs of Department of Defense facilities in Colorado and Wyoming.

  3. American Recovery and Reinvestment Act (ARRA) FEMP Technical Assistance U.S. Army – Project 276 Renewable Resource Development on Department of Defense Bases in Alaska: Challenges and Opportunities

    Energy Technology Data Exchange (ETDEWEB)

    Warwick, William M.

    2010-09-30

    The potential to increase utilization of renewable energy sources among military facilities in Alaska through coordinated development and operation is the premise of this task. The US Army Pacific Command requested assistance from PNNL to help develop a more complete understanding of the context for wheeling power within Alaska, including legal and regulatory barriers that may prohibit the DOD facilities from wheeling power among various locations to optimize the development and use of renewable resources.

  4. LEX Project

    DEFF Research Database (Denmark)

    Damkilde, Lars; Larsen, Torben J.; Walbjørn, Jacob

    This document is aimed at helping all parties involved in the LEX project to get a common understanding of words, process, levels and the overall concept.......This document is aimed at helping all parties involved in the LEX project to get a common understanding of words, process, levels and the overall concept....

  5. OMEGA project

    International Nuclear Information System (INIS)

    Shibuya, E.H.

    1989-01-01

    The OMEGA - Observation of Multiple particle production, Exotic Interactions and Gamma-ray Air Shower-project is presented. The project try to associate photosensitive detectors from experiences of hadronic interactions with electronic detectors used by experiences that investigate extensive atmospheric showers. (M.C.K.)

  6. Watchdog Project

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Rhett [Schweitzer Engineering Laboratories, Inc., Pullman, WA (United States); Campbell, Jack [CenterPoint Energy Houston Electric, TX (United States); Hadley, Mark [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-12-30

    The Watchdog Project completed 100% of the project Statement of Project Objective (SOPO). The Watchdog project was a very aggressive project looking to accomplish commercialization of technology that had never been commercialized, as a result it took six years to complete not the original three that were planned. No additional federal funds were requested from the original proposal and SEL contributed the additional cost share required to complete the project. The result of the Watchdog Project is the world’s first industrial rated Software Defined Network (SDN) switch commercially available. This technology achieved the SOPOO and DOE Roadmap goals to have strong network access control, improve reliability and network performance, and give the asset owner the ability to minimize attack surface before and during an attack. The Watchdog project is an alliance between CenterPoint Energy Houston Electric, Pacific Northwest National Laboratories (PNNL), and Schweitzer Engineering Laboratories, Inc. (SEL). SEL is the world’s leader in microprocessor-based electronic equipment for protecting electric power systems. PNNL performs basic and applied research to deliver energy, environmental, and national security for our nation. CenterPoint Energy is the third largest publicly traded natural gas delivery company in the U.S and third largest combined electricity and natural gas delivery company. The Watchdog Project efforts were combined with the SDN Project efforts to produce the entire SDN system solution for the critical infrastructure. The Watchdog project addresses Topic Area of Interest 5: Secure Communications, for the DEFOA- 0000359 by protecting the control system local area network itself and the communications coming from and going to the electronic devices on the local network. Local area networks usually are not routed and have little or no filtering capabilities. Combine this with the fact control system protocols are designed with inherent trust the control

  7. Molecular cloning of a preprohormone from Hydra magnipapillata containing multiple copies of Hydra-L Wamide (Leu-Trp-NH2) neuropeptides: evidence for processing at Ser and Asn residues

    DEFF Research Database (Denmark)

    Leviev, I; Williamson, M; Grimmelikhuijzen, C J

    1997-01-01

    The simple, freshwater polyp Hydra is often used as a model to study development in cnidarians. Recently, a neuropeptide, metamorphosis in a hydroid planula larva to become a polyp. Here, we have cloned a preprohormone...... from Hydra magnipapillata containing 11 (eight different) immature neuropeptide sequences that are structurally related to the metamorphosis-inducing neuropeptide from sea anermones. During the final phase of our cloning experiments, another research team independently isolated and sequenced five...... most frequent one being Gly-Pro-Pro-Pro-Gly-Leu-Trp-NH2; Hydra-LWamide l; three copies). Based on their structural similarities with the metamorphosis-inducing neuropeptide from sea anemones, the mature peptides derived from the Hydra-LWamide preprohormone are potential candidates for being...

  8. Freedom Project

    Directory of Open Access Journals (Sweden)

    Alejandra Suarez

    2014-02-01

    Full Text Available Freedom Project trains prisoners in nonviolent communication and meditation. Two complementary studies of its effects are reported in this article. The first study is correlational; we found decreased recidivism rates among prisoners trained by Freedom Project compared with recidivism rates in Washington state. The second study compared trained prisoners with a matched-pair control group and found improvement in self-reported anger, self-compassion, and certain forms of mindfulness among the trained group. Ratings of role-plays simulating difficult interactions show increased social skills among the group trained by Freedom Project than in the matched controls.

  9. Recombinant Rhipicephalus appendiculatus gut (Ra86 and salivary gland cement (Trp64 proteins as candidate antigens for inclusion in tick vaccines: protective effects of Ra86 on infestation with adult R. appendiculatus

    Directory of Open Access Journals (Sweden)

    Saimo M

    2011-11-01

    Full Text Available Margaret Saimo1,2,*, David O Odongo3,4,*, Stephen Mwaura3, Just M Vlak1, Anthony J Musoke5, George W Lubega2, Richard P Bishop3, Monique M van Oers11Laboratory of Virology, Wageningen University, Wageningen, The Netherlands; 2School of Veterinary Medicine, Makerere University, Kampala, Uganda; 3International Livestock Research Institute, Nairobi, Kenya; 4School of Biological Sciences, University of Nairobi, Nairobi, Kenya; 5Onderstepoort Veterinary Institute, Onderstepoort, Pretoria, South Africa *These two authors made an equal contribution to this workAbstract: Rhipicephalus appendiculatus gut protein Ra86 (variants Ra85A and Ra92A and the salivary gland cement protein (Trp64 were expressed in the baculovirus-insect cell system. The recombinant gut proteins expressed as soluble proteins and the recombinant cement protein, as insoluble inclusion bodies, were used to immunize rabbits, which were then challenged with larval, nymphal, and adult stages of R. appendiculatus ticks. High tick mortality (23.3% occurred on adult ticks that fed on rabbits vaccinated with the gut proteins, compared with 1.9% mortality in ticks that fed on unvaccinated naïve control rabbits. The mean weight of engorged female ticks was significantly reduced by 31.5% in rabbits vaccinated with the Ra86 recombinant protein compared with controls, as was egg production. Marked effects on these parameters were also observed in adult ticks as a result from vaccination using Trp64, but these were not statistically significant. For both antigens, there was no demonstrable effect on larval or nymphal ticks. This study demonstrates for the first time the protective efficacy of a homolog of Boophilus microplus Bm86 in reducing tick infestation by the adult stage of the three-host tick R. appendiculatus. The results demonstrate the potential of Ra86 for vaccine development against this tick and for the control of East Coast fever.Keywords: baculovirus, Ra85A, Ra92A, Boophilus

  10. Exprese GluN1C2 podjednotky NMDA receptoru v hipokampu pacientů trpících schizofrenií - studie post mortem

    Czech Academy of Sciences Publication Activity Database

    Vrajová, M.; Horáček, J.; Klaschka, Jan

    2010-01-01

    Roč. 14, Suppl. 2 (2010), s. 10-11 ISSN 1211-7579 R&D Projects: GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z10300504 Keywords : schizophrenia * hippocampus * GluN1 C2 subunit of NMDA receptor Subject RIV: FL - Psychiatry, Sexuology

  11. EBFA project

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    An engineering project office was established during the fall of 1976 to manage and coordinate all of the activities of the Electron Beam Fusion Project. The goal of the project is to develop the Electron Beam Fusion Accelerator (EBFA) and its supporting systems, and integrate these systems into the new Electron Beam Fusion Facility (EBFF). Supporting systems for EBFA include a control/monitor system, a data acquistion/automatic data processing system, the liquid transfer systems, the insulating gas transfer systems, etc. Engineers and technicians were assigned to the project office to carry out the engineering design, initiate procurement, monitor the fabrication, perform the assembly and to assist the pulsed power research group in the activation of the EBFA

  12. Project Reptile!

    Science.gov (United States)

    Diffily, Deborah

    2001-01-01

    Integrating curriculum is important in helping children make connections within and among areas. Presents a class project for kindergarten children which came out of the students' interests and desire to build a reptile exhibit. (ASK)

  13. Project Soar.

    Science.gov (United States)

    Austin, Marion

    1982-01-01

    Project Soar, a Saturday enrichment program for gifted students (6-14 years old), allows students to work intensively in a single area of interest. Examples are cited of students' work in crewel embroidery, creative writing, and biochemistry. (CL)

  14. EUROFANCOLEN Project

    International Nuclear Information System (INIS)

    Bueren, J. A.

    2014-01-01

    The first follow-up report of European Project EUROFANCOLEN, the purpose of which is to develop a gene therapy clinical trial to resolve bone marrow failure in patients with a genetic disease known as Fanconi anemia (FA), was sent to the European Commission in September. The main objective of project EUROFANCOLEN is to develop a gene therapy trial for patients with Fanconi anemia Type A (FA-A), which affects 80% of the patients with FA in Spain. (Author)

  15. Project Management

    DEFF Research Database (Denmark)

    Kampf, Constance

    2009-01-01

    In this video Associate Professor Constance Kampf talks about the importance project management. Not only as a tool in implementation, but also as a way of thinking, and as something that needs to be considered from idea conception......In this video Associate Professor Constance Kampf talks about the importance project management. Not only as a tool in implementation, but also as a way of thinking, and as something that needs to be considered from idea conception...

  16. Assessing the Potential of Social Networks as a Means for Information Diffusion the Weatherization Experiences (WE) Project.

    Energy Technology Data Exchange (ETDEWEB)

    Rose, Erin M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hawkins, Beth A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-04-01

    In April 2009, U.S. Department of Energy (DOE) formally tasked Oak Ridge National Laboratory (ORNL) with conducting two impact and process evaluations of DOE’s Weatherization Assistance Program (WAP), known as the retrospective and American Recovery and Reinvestment Act of 2009 (ARRA) period evaluations, respectively. The former focused on WAP Program Year (PY) 2008, which covers the period from April 2008 to June 2009. The latter focused on PY 2010. This report presents in-depth analyses from ORNL’s social network study, the Weatherization Experiences (WE) Project, an exploratory study conducted as part of the ARRA period WAP evaluation. The WE Project explored the potential for WAP recipients and staff to influence energy savings beyond their homes and day jobs. Several studies conducted through ORNL’s evaluation of WAP found that the program has the ability to profoundly impact the lives of the people it serves (Tonn et al. 2014b). Recipients of WAP provided statements ranging from the newfound ability to pay utility bills and prescription medication to reduced emergency department visits for asthma and medical conditions associated with thermal stress. Through this exploratory research project, the stories of hundreds of weatherization recipients and providers were documented. The WE Project was designed to further investigate whether or not shared experiences with weatherization have the power to stimulate home energy saving action within an individual’s social network.

  17. Project mobilisation

    International Nuclear Information System (INIS)

    Clark, J.; Limbrick, A.

    1996-01-01

    This paper identifies and reviews the issues to be addressed and the procedures to be followed during the mobilisation of projects using LFG as an energy source. Knowledge of the procedures involved in project mobilisation, their sequence and probable timescales, is essential for efficient project management. It is assumed that the majority of projects will be situated on existing, licensed landfill sites and, in addition to complying with the relevant conditions of the waste management licence and original planning consent, any proposed developments on the site will require a separate planning consent. Experience in the UK indicates that obtaining planning permission rarely constitutes a barrier to the development of schemes for the utilisation of LFG. Even so, an appreciation of the applicable environmental and planning legislation is essential as this will enable the developer to recognise the main concerns of the relevant planning authority at an early stage of the project, resulting in the preparation of an informed and well-structured application for planning permission. For a LFG utilisation scheme on an existing landfill site, the need to carry out an environmental assessment (EA) as part of the application for planning permission will, in vitually all cases, be discretionary. Even if not deemed necessary by the planning authority, an EA is a useful tool at the planning application stage, to identify and address potential problems and to support discussions with bodies such as the Environment Agency, from whom consents or authorisations may be required. Carrying out an EA can thus provide for more cost-effective project development and enhanced environmental protection. Typically, the principal contractual arrangements, such as the purchase of gas or the sale of electricity, will have been established before the project mobilisation phase. However, there are many other contractural arrangements that must be established, and consents and permits that may be

  18. Projective mapping

    DEFF Research Database (Denmark)

    Dehlholm, Christian; Brockhoff, Per B.; Bredie, Wender Laurentius Petrus

    2012-01-01

    by the practical testing environment. As a result of the changes, a reasonable assumption would be to question the consequences caused by the variations in method procedures. Here, the aim is to highlight the proven or hypothetic consequences of variations of Projective Mapping. Presented variations will include...... instructions and influence heavily the product placements and the descriptive vocabulary (Dehlholm et.al., 2012b). The type of assessors performing the method influences results with an extra aspect in Projective Mapping compared to more analytical tests, as the given spontaneous perceptions are much dependent......Projective Mapping (Risvik et.al., 1994) and its Napping (Pagès, 2003) variations have become increasingly popular in the sensory field for rapid collection of spontaneous product perceptions. It has been applied in variations which sometimes are caused by the purpose of the analysis and sometimes...

  19. Isotopes Project

    International Nuclear Information System (INIS)

    Dairiki, J.M.; Browne, E.; Firestone, R.B.; Lederer, C.M.; Shirley, V.S.

    1984-01-01

    The Isotopes Project compiles and evaluates nuclear structure and decay data and disseminates these data to the scientific community. From 1940-1978 the Project had as its main objective the production of the Table of Isotopes. Since publication of the seventh (and last) edition in 1978, the group now coordinates its nuclear data evaluation efforts with those of other data centers via national and international nuclear data networks. The group is currently responsible for the evaluation of mass chains A = 167-194. All evaluated data are entered into the International Evaluated Nuclear Structure Data File (ENSDF) and are published in Nuclear Data Sheets. In addition to the evaluation effort, the Isotopes Project is responsible for production of the Radioactivity Handbook

  20. LLAMA Project

    Science.gov (United States)

    Arnal, E. M.; Abraham, Z.; Giménez de Castro, G.; de Gouveia dal Pino, E. M.; Larrarte, J. J.; Lepine, J.; Morras, R.; Viramonte, J.

    2014-10-01

    The project LLAMA, acronym of Long Latin American Millimetre Array is very briefly described in this paper. This project is a joint scientific and technological undertaking of Argentina and Brazil on the basis of an equal investment share, whose mail goal is both to install and to operate an observing facility capable of exploring the Universe at millimetre and sub/millimetre wavelengths. This facility will be erected in the argentinean province of Salta, in a site located at 4830m above sea level.

  1. Retro operation on the Trp-cage miniprotein sequence produces an unstructured molecule capable of folding similar to the original only upon 2,2,2-trifluoroethanol addition

    Czech Academy of Sciences Publication Activity Database

    Vymětal, Jiří; Bathula, S. R.; Černý, Jiří; Chaloupková, R.; Žídek, L.; Sklenář, V.; Vondrášek, Jiří

    2014-01-01

    Roč. 27, č. 12 (2014), s. 463-472 ISSN 1741-0126 R&D Projects: GA MŠk(CZ) LH11020; GA ČR GA203/08/0114 Grant - others:GA MŠk(CZ) LO1214; GA MŠk(CZ) LM2010005; GA MŠk(CZ) ED1.1.00/02.0068 Program:ED Institutional support: RVO:61388963 ; RVO:86652036 Keywords : protein folding * protein-structure prediction * molecular dynamics * NMR methods * CD spectroscopy Subject RIV: CE - Biochemistry Impact factor: 2.537, year: 2014

  2. Project Avatar

    DEFF Research Database (Denmark)

    Juhlin, Jonas Alastair

    'Project Avatar' tager udgangspunkt i den efterretningsdisciplin, der kaldes Open Source Intelligence og indebærer al den information, som ligger frit tilgængeligt i åbne kilder. Med udbredelsen af sociale medier åbners der op for helt nye typer af informationskilder. Spørgsmålet er; hvor nyttig er...

  3. Project Baltia

    Index Scriptorium Estoniae

    2007-01-01

    Uus arhitektuuriajakiri "Project Baltia" tutvustab Baltimaade, Soome ja Peterburi regiooni arhitektuuri, linnaehitust ja disaini. Ilmub neli korda aastas inglise- ja venekeelsena. Väljaandja: kirjastus Balticum Peterburis koostöös Amsterdami ja Moskva kirjastusega A-Fond. Peatoimetaja Vladimir Frolov

  4. Tedese Project

    Science.gov (United States)

    Buforn, E.; Davila, J. Martin; Bock, G.; Pazos, A.; Udias, A.; Hanka, W.

    The TEDESE (Terremotos y Deformacion Cortical en el Sur de España) project is a joint project of the Universidad Complutense de Madrid (UCM) and Real Instituto y Observatorio de la Armada de San Fernando, Cadiz (ROA) supported by the Spanish Ministerio de Ciencia y Tecnologia with the participation of the GeoforschungZen- trum, Potsdam (GFZ). The aim is to carry out a study of the characteristics of the oc- currence and mechanism of earthquakes together with measurements of crustal struc- ture and deformations in order to obtain an integrated evaluation of seismic risk in southern Spain from. As part of this project a temporal network of 10 broad-band seismological stations, which will complete those already existing in the zone, have been installed in southern Spain and northern Africa for one year beginning in October 2001. The objectives of the project are the study in detail of the focal mechanisms of earthquakes in this area, of structural in crust and upper mantle, of seismic anisotropy in crust and mantle as indicator for tectonic deformation processed and the measure- ments of crustal deformations using techniques with permanent GPS and SLR stations and temporary GPS surveys. From these studies, seismotectonic models and maps will be elaborated and seismic risk in the zone will be evaluated.

  5. Project Boomerang

    Science.gov (United States)

    King, Allen L.

    1975-01-01

    Describes an experimental project on boomerangs designed for an undergraduate course in classical mechanics. The students designed and made their own boomerangs, devised their own procedures, and carried out suitable measurements. Presents some of their data and a simple analysis for the two-bladed boomerang. (Author/MLH)

  6. Project Narrative

    Energy Technology Data Exchange (ETDEWEB)

    Driscoll, Mary C. [St. Bonaventure University, St Bonaventure, NY(United States)

    2012-07-12

    The Project Narrative describes how the funds from the DOE grant were used to purchase equipment for the biology, chemistry, physics and mathematics departments. The Narrative also describes how the equipment is being used. There is also a list of the positive outcomes as a result of having the equipment that was purchased with the DOE grant.

  7. Radiochemistry Project

    International Nuclear Information System (INIS)

    Anon.

    Researches carried out in the 'Radiochemistry Project' of the Agricultural Nuclear Energy Center, Piracicaba, Sao Paulo State, Brazil, are described. Such researches comprise: dosimetry and radiological protection; development of techniques and methods of chemical analysis and radiochemistry. (M.A.) [pt

  8. FLOAT Project

    DEFF Research Database (Denmark)

    Sørensen, Eigil V.; Aarup, Bendt

    The objective of the FLOAT project is to study the reliability of high-performance fibre-reinforced concrete, also known as Compact Reinforced Composite (CRC), for the floats of wave energy converters. In order to reach a commercial breakthrough, wave energy converters need to achieve a lower price...

  9. Hydrology Project

    International Nuclear Information System (INIS)

    Anon.

    Research carried out in the 'Hydrology Project' of the Centro de Energia Nuclear na Agricultura', Piracicaba, Sao Paulo State, Brazil, are described. Such research comprises: Amazon hydrology and Northeast hydrology. Techniques for the measurement of isotope ratios are used. (M.A.) [pt

  10. CHEMVAL project

    International Nuclear Information System (INIS)

    Chandratillake, M.; Falck, W.E.; Read, D.

    1992-01-01

    This report summarises the development history of the CHEMVAL Thermodynamic Database, the criteria employed for data selection and the contents of Version 4.0, issued to participants on the completion of the project. It accompanies a listing of the database constructed using the dBase III + /IV database management package. (Author)

  11. Project COLD.

    Science.gov (United States)

    Kazanjian, Wendy C.

    1982-01-01

    Describes Project COLD (Climate, Ocean, Land, Discovery) a scientific study of the Polar Regions, a collection of 35 modules used within the framework of existing subjects: oceanography, biology, geology, meterology, geography, social science. Includes a partial list of topics and one activity (geodesic dome) from a module. (Author/SK)

  12. Swedish projects

    International Nuclear Information System (INIS)

    Thunell, J.

    1993-01-01

    The main sources of the financing of Swedish research on gas technology are listed in addition to names of organizations which carry out this research. The titles and descriptions of the projects carried out are presented in addition to lists of reports published with information on prices. (AB)

  13. SDN Project

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Rhett [Schweitzer Engineering Laboratories Inc, Pullman, WA (United States)

    2016-12-23

    The SDN Project completed on time and on budget and successfully accomplished 100% of the scope of work outlined in the original Statement of Project Objective (SOPO). The SDN Project formed an alliance between Ameren Corporation, University of Illinois Urbana- Champaign (UIUC), Pacific Northwest National Laboratories (PNNL), and Schweitzer Engineering Laboratories, Inc. (SEL). The objective of the SDN Project is to address Topic Area of Interest 2: Sustain critical energy delivery functions while responding to a cyber-intrusion under Funding Opportunity Announcement DE-FOA-0000797. The goal of the project is to design and commercially release technology that provides a method to sustain critical energy delivery functions during a cyber intrusion and to do this control system operators need the ability to quickly identify and isolate the affected network areas, and re-route critical information and control flows around. The objective of the SDN Project is to develop a Flow Controller that monitors, configures, and maintains the safe, reliable network traffic flows of all the local area networks (LANs) on a control system in the Energy sector. The SDN team identified the core attributes of a control system and produced an SDN flow controller that has the same core attributes enabling networks to be designed, configured and deployed that maximize the whitelisted, deny-bydefault and purpose built networks. This project researched, developed and commercially released technology that: Enables all field networks be to configured and monitored as if they are a single asset to be protected; Enables greatly improved and even precalculated response actions to reliability and cyber events; Supports pre-configured localized response actions tailored to provide resilience against failures and centralized response to cyber-attacks that improve network reliability and availability; Architecturally enables the right subject matter experts, who are usually the information

  14. Projective geometry and projective metrics

    CERN Document Server

    Busemann, Herbert

    2005-01-01

    The basic results and methods of projective and non-Euclidean geometry are indispensable for the geometer, and this book--different in content, methods, and point of view from traditional texts--attempts to emphasize that fact. Results of special theorems are discussed in detail only when they are needed to develop a feeling for the subject or when they illustrate a general method. On the other hand, an unusual amount of space is devoted to the discussion of the fundamental concepts of distance, motion, area, and perpendicularity.Topics include the projective plane, polarities and conic sectio

  15. Projective measure without projective Baire

    DEFF Research Database (Denmark)

    Schrittesser, David; Friedman, Sy David

    We prove that it is consistent (relative to a Mahlo cardinal) that all projective sets of reals are Lebesgue measurable, but there is a ∆13 set without the Baire property. The complexity of the set which provides a counterexample to the Baire property is optimal.......We prove that it is consistent (relative to a Mahlo cardinal) that all projective sets of reals are Lebesgue measurable, but there is a ∆13 set without the Baire property. The complexity of the set which provides a counterexample to the Baire property is optimal....

  16. Pacific Northwest Smart Grid Demonstration Project Technology Performance Report Volume 1: Technology Performance

    Energy Technology Data Exchange (ETDEWEB)

    Melton, Ron [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-06-01

    The Pacific Northwest Smart Grid Demonstration (PNWSGD), a $179 million project that was co-funded by the U.S. Department of Energy (DOE) in late 2009, was one of the largest and most comprehensive demonstrations of electricity grid modernization ever completed. The project was one of 16 regional smart grid demonstrations funded by the American Recovery and Reinvestment Act. It was the only demonstration that included multiple states and cooperation from multiple electric utilities, including rural electric co-ops, investor-owned, municipal, and other public utilities. No fewer than 55 unique instantiations of distinct smart grid systems were demonstrated at the projects’ sites. The local objectives for these systems included improved reliability, energy conservation, improved efficiency, and demand responsiveness. The demonstration developed and deployed an innovative transactive system, unique in the world, that coordinated many of the project’s distributed energy resources and demand-responsive components. With the transactive system, additional regional objectives were also addressed, including the mitigation of renewable energy intermittency and the flattening of system load. Using the transactive system, the project coordinated a regional response across the 11 utilities. This region-wide connection from the transmission system down to individual premises equipment was one of the major successes of the project. The project showed that this can be done and assets at the end points can respond dynamically on a wide scale. In principle, a transactive system of this type might eventually help coordinate electricity supply, transmission, distribution, and end uses by distributing mostly automated control responsibilities among the many distributed smart grid domain members and their smart devices.

  17. Project Radon

    International Nuclear Information System (INIS)

    Ekholm, S.

    1988-01-01

    The project started in March 1987. The objective is to perform radon monitoring in 2000 dwellings occupied by people employed by State Power Board and to continue to contribute to the development of radon filters. The project participates in developing methods for radon measurement and decontamination and in adapting the methods to large scale application. About 400 so called radon trace measurements (coarse measurement) and about 10 action measurements (decontamination measurement) have been made so far. Experience shows that methods are fully applicable and that the decontamination measures recommended give perfectly satisfactory results. It is also established that most of the houses with high radon levels have poor ventilation Many of them suffer from moisture and mould problems. The work planned for 1988 and 1989 will in addition to measurements be directed towards improvement of the measuring methods. An activity catalogue will be prepared in cooperation with ventilation enterprises. (O.S.)

  18. PARTNER Project

    CERN Multimedia

    Ballantine, A; Dixon-Altaber, H; Dosanjh, M; Kuchina, L

    2011-01-01

    Hadrontherapy uses particle beams to treat tumours located near critical organs and tumours that respond poorly to conventional radiation therapy. It has become evident that there is an emerging need for reinforcing research in hadrontherapy and it is essential to train professionals in this rapidly developing field. PARTNER is a 4-year Marie Curie Training project funded by the European Commission with 5.6 million Euros aimed at the creation of the next generation of experts. Ten academic institutes and research centres and two leading companies are participating in PARTNER, that is coordinated by CERN, forming a unique multidisciplinary and multinational European network. The project offers research and training opportunities to 25 young biologists, engineers, physicians and physicists and is allowing them to actively develop modern techniques for treating cancer in close collaboration with leading European Institutions. For this purpose PARTNER relies on cutting edge research and technology development, ef...

  19. Swedish projects

    International Nuclear Information System (INIS)

    Thunell, J.

    1992-01-01

    A description is given of research activities, concerning heating systems, which were carried out in Sweden during 1991. The main subject areas dealt with under the gas technology group within the area of heating systems were catalytic combustion, polyethylene materials, and gas applications within the paper and pulp industries. A list is given of the titles of project reports published during 1991 and of those begun during that year. Under the Swedish Centre for Gas Technology (SGC), the main areas of research regarding gas applications were polyethylene materials, industrial applications and the reduction of pollutant emissions. A detailed list is given of research projects which were in progress or proposed by March 1992 under the heating system gas technology research group in Sweden. This list also presents the aims and descriptions of the methods, etc. (AB)

  20. AVE project

    International Nuclear Information System (INIS)

    2004-01-01

    During 1998, ANAV began to optimize Human Resources to cope with the ERE and ANA-ANV integration. Project AVE was intended to achieve an orderly transfer of know-how, skills, attitudes and experiences. The most complex part was renovation of personnel with Operating Licenses. Nearly 140 people had joined the organization by late December 2003. This opportunity was seized to draw up a new Training Manual, and a common Initial Training Plan was designed for the two plants, accounting for the singularities of each one. The plan is divided into 5 modules: Common Training, Specific Training, PEI/CAT, Management, and on-the-job Training. The training environments were defined according to the nature of the capabilities to be acquired. Project AVE resulted in the merger of the Asco and Vandellos II Training services. (Author)

  1. Spent Nuclear Fuel project, project management plan

    International Nuclear Information System (INIS)

    Fuquay, B.J.

    1995-01-01

    The Hanford Spent Nuclear Fuel Project has been established to safely store spent nuclear fuel at the Hanford Site. This Project Management Plan sets forth the management basis for the Spent Nuclear Fuel Project. The plan applies to all fabrication and construction projects, operation of the Spent Nuclear Fuel Project facilities, and necessary engineering and management functions within the scope of the project

  2. ARTIST Project

    CSIR Research Space (South Africa)

    Ferguson, K

    2012-10-01

    Full Text Available Biennial Conference Presented by: Keith Ferguson Date: 9 October 2012 Mobile IPTV Broadcasting Platform Consortium: CSIR, UCT, ECA Funded by TIA 2008-2011 ARTIST Project Min time - sacrifice quality Max quality - sacrifice time Application Context... idth > ARTIST Platform Advertiser Client 1 Client 2 Client 3 Client 4 Sport channel News channel Wildlife channel Advert database Transaction database Transcoder Servers Media Switching Servers INTERNET Channel viewing Advert upload...

  3. CARA project

    International Nuclear Information System (INIS)

    Bergallo, Juan E.; Brasnarof, Daniel O.

    2000-01-01

    The CARA (Advanced Fuels for Argentine Reactors) Project successfully completed its first stage, phase one, last year. The performance of this fuel has been partially examined, using CNEA and CONUAR facilities and personnel. With the results obtained in this stage, determined by the corresponding tests and verification of the fuel behavior, the performance of the second stage started immediately afterwards. Works performed and results obtained during the development of the second stage are generally described in this paper. (author)

  4. Polytope projects

    CERN Document Server

    Iordache, Octavian

    2013-01-01

    How do you know what works and what doesn't? This book contains case studies highlighting the power of polytope projects for complex problem solving. Any sort of combinational problem characterized by a large variety of possibly complex constructions and deconstructions based on simple building blocks can be studied in a similar way. Although the majority of case studies are related to chemistry, the method is general and equally applicable to other fields for engineering or science.

  5. Projection Methods

    DEFF Research Database (Denmark)

    Wagner, Falko Jens; Poulsen, Mikael Zebbelin

    1999-01-01

    When trying to solve a DAE problem of high index with more traditional methods, it often causes instability in some of the variables, and finally leads to breakdown of convergence and integration of the solution. This is nicely shown in [ESF98, p. 152 ff.].This chapter will introduce projection...... methods as a way of handling these special problems. It is assumed that we have methods for solving normal ODE systems and index-1 systems....

  6. Project Phaseolus

    International Nuclear Information System (INIS)

    Anon.

    Research carried out through the Phaseolus Project of the 'Centro de Energia Nuclear na Agricultura' (CENA) Piracicaba, Sao Paulo State, Brazil, is described. It comprises the following subject s: plant breeding; nitrogen fixation; tissue cultures; proteins; photosynthetic efficiency; soil-plant interactions; electron microscopy of the golden mosaic virus; pest control; production of 15 N-enriched ammonium sulfate, and determination of elements in the beans plant. (M.A.) [pt

  7. Numatron project

    Energy Technology Data Exchange (ETDEWEB)

    Sugimoto, K [Osaka Univ., Toyonaka (Japan). Dept. of Physics; Hirao, Yasuo

    1977-04-01

    A project of high energy heavy ion acceleration is under consideration. The high energy heavy ions can produce highly condensed states of nuclei. A new phase of nucleus would be seen at the incident energy higher than 140 MeV/nucleon. High energy heavy ions causing high density states and meson emission will produce various new nuclides. Process of formation of atomic elements will be studied. Various fields of science can be also investigated by the high energy heavy ions. Spectroscopic study of multi-valent ions will be made high energy uranium. Study of materials for the fusion reactor is important. Impurity heavy ion from the wall of the fusion reactor may lose the energy of the reactor, and the characteristic features of heavy ions should be investigated. The highly ionized states of atoms are also produced by heavy ion injection into material. Several projects of heavy ion acceleration are in progress in the world. The Numatron project in Japan is to construct a combination machine of a Cockcroft type machine, three linear accelerator and a synchrotron. The planned energy of the machine is 670 MeV/nucleon. Technical problems are under investigation.

  8. Coloss project

    International Nuclear Information System (INIS)

    2005-01-01

    The COLOSS project was a shared-cost action, co-ordinated by IRSN within the Euratom Research Framework Programme 1998-2002. Started in February 2000, the project lasted three years. The work-programme performed by 19 partners was shaped around complementary activities aimed at improving severe accident codes. Unresolved risk-relevant issues regarding H2 production, melt generation and the source term were studied, through a large number of experiments such as a) dissolution of fresh and high burn-up UO 2 and MOX by molten Zircaloy, b) simultaneous dissolution of UO 2 and ZrO 2 by molten Zircaloy, c) oxidation of U-O-Zr mixtures by steam, d) degradation-oxidation of B 4 C control rods. Significant results have been produced from separate-effects, semi-global and large-scale tests on COLOSS topics. Break-through were achieved on some issues. Nevertheless, more data are needed for consolidation of the modelling on burn-up effects on UO 2 and MOX dissolution and on oxidation of U-O-Zr and B 4 C-metal mixtures. There was experimental evidence that the oxidation of these mixtures can contribute significantly to the large H2 production observed during the reflooding of degraded cores under severe accident conditions. Based on the experimental results obtained on the COLOSS topics, corresponding models were developed and were successfully implemented in several severe accident codes. Upgraded codes were then used for plant calculations to evaluate the consequences of new models on key severe accident sequences occurring in different plants designs involving B 4 C control rods (EPR, BWR, VVER- 1000) as well as in the TMI-2 accident. The large series of plant calculations involved sensitivity studies and code benchmarks. Main severe accident codes in use in the EU for safety studies were used such as ICARE/CATHARE, SCDAP/RELAP5, ASTEC, MELCOR and MAAP4. This activity enabled: a) the assessment of codes to calculate core degradation, b) the identification of main

  9. U.S. Energy Service Company Industry: Market Size and Project Performance from 1990-2008

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, Peter; Goldman, Charles; Satchwell, Andrew

    2012-08-21

    The U.S. energy service company (ESCO) industry is an example of a private sector business model where energy savings are delivered to customers primarily through the use of performance-based contracts. This study was conceived as a snapshot of the ESCO industry prior to the economic slowdown and the introduction of federal stimulus funding mandated by enactment of the American Recovery and Reinvestment Act of 2009 (ARRA). This study utilizes two parallel analytic approaches to characterize ESCO industry and market trends in the U.S.: (1) a ?top-down? approach involving a survey of individual ESCOs to estimate aggregate industry activity and (2) a ?bottom-up? analysis of a database of ~;;3,250 projects (representing over $8B in project investment) that reports market trends including installed EE retrofit strategies, project installation costs and savings, project payback times, and benefit-cost ratios over time. Despite the onset of a severe economic recession, the U.S. ESCO industry managed to grow at about 7percent per year between 2006 and 2008. ESCO industry revenues were about $4.1 billion in 2008 and ESCOs anticipate accelerated growth through 2011 (25percent per year). We found that 2,484 ESCO projects in our database generated ~;;$4.0 billion ($2009) in net, direct economic benefits to their customers. We estimate that the ESCO project database includes about 20percent of all U.S. ESCO market activity from 1990-2008. Assuming the net benefits per project are comparable for ESCO projects that are not included in the LBNL database, this would suggest that the ESCO industry has generated ~;;$23 billion in net direct economic benefits for customers at projects installed between 1990 and 2008. There is empirical evidence confirming that the industry is evolving by installing more comprehensive and complex measures?including onsite generation and measures to address deferred maintenance?but this evolution has significant implications for customer project

  10. Conceptual Design of Main Cooling System for a Fusion Power Reactor with Water Cooled Lithium-Lead Blanket. TW1-TRP-PPCS1, Deliverable 8

    International Nuclear Information System (INIS)

    Natalizio, Antonio; Collen, Jan

    2002-06-01

    The HTS (Heat Transfer System) conceptual design developed for the PPCS (Power-Plant Conceptual Study) plant model is compliant with the single failure criterion - i.e., the failure of a single active component (e.g., pump) will not cause the reactor to shutdown. The system effective availability (capacity factor), however, is only marginally better than that of the SEAFP design, as the number of loops could not be decreased further, due to coolant inventory limitations. The PPCS Plant Model A has about 70 % more fusion power than the SEAFP model. Therefore, keeping the same number of loops as in the SEAFP model would have implied a 70 % larger inventory. To improve plant availability and safety, however, the number of blanket and first wall loops have been reduced from eight to six, implying a further increase in loop inventory of about 25 %. For these and other reasons, the coolant inventory, at risk from a loss-of-coolant accident, has increased significantly, relative to the SEAFP design (∼130 vs. 50 m 3 ). The proposed heat transport system conceptual design meets, or exceeds, all project specifications

  11. Development of a Standard Methodology for the Quantitative Measurement of Steel Phase Transformation Kinetics and Dilation Strains Using Dilatometric Methods, QMST (TRP 0015)

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Manish Metha; Dr. Tom Oakwood

    2004-04-28

    The purpose of this collaborative project was to develop a standard practice for obtaining and archiving quantitative steel transformation kinetic data and thermal strain data. Two families of dilatometric equipment were employed to develop this standard practice for testing bar product steels. These include high-speed quenching and deformation dilatometers and Gleeble{reg_sign} thermomechanical simulation instruments. Standard measurement, data interpretation and data reporting methods were developed and defined by the cross-industry QMST Consortium members consisting of steel-manufacturers, forgers, heat-treaters, modelers, automotive and heavy vehicle OEMs along with team expert technologists from the National Labs and academia. The team designed phase transformation experiments on two selected steel grades to validate the standard practices--a medium carbon grade SAE 1050 and an alloy steel SAE 8620. A final standard practice document was developed based on the two dilatometry methods, and was submitted to and approved by ASTM (available as A1033-04). The standard practice specifies a method for measuring austenite transformation under no elastic stress or plastic deformation. These methods will be an enabler for the development and electronic archiving of a quantitative database for process modeling using computer simulation software, and will greatly assist endusers in developing accurate process and product simulations during the thermo-mechanical processing of bar and rod product steels.

  12. 75 FR 36016 - Community Reinvestment Act Regulations

    Science.gov (United States)

    2010-06-24

    ... tracts affected by high levels of loan delinquencies and foreclosures. Among the many consequences of... homes in default or delinquency in each State or unit of general local government. Under NSP1, each of... Congressional intent that the funds have maximum impact and be targeted to States and local communities with the...

  13. 75 FR 61035 - Community Reinvestment Act Regulations

    Science.gov (United States)

    2010-10-04

    ... Education Lending by Financial Institutions Several commenters noted that education lending, particularly private education lending, is a specialized type of lending engaged in by only a few financial... education loans as including loans originated by financial institutions through a program of the U.S...

  14. 75 FR 57330 - Community Reinvestment Act

    Science.gov (United States)

    2010-09-20

    ... mergers, branches, and certain other corporate activities. Further, the CRA statute requires the Agencies to issue regulations to carry out its purposes. OTS uses the data collected under the CRA regulations... institution's CRA performance and to participate meaningfully in the application process. Type of Review...

  15. 78 FR 79283 - Community Reinvestment Act Regulations

    Science.gov (United States)

    2013-12-30

    ... by reference to asset-size criteria expressed in dollar amounts, and they further require the....C. 553(b)(B) of the Administrative Procedure Act (APA), an agency may, for good cause, find (and.... Under 5 U.S.C. 553(d)(3) of the APA, the required publication or service of a substantive rule shall be...

  16. Working together : transportation opportunities for technology reinvestment

    Science.gov (United States)

    1993-05-10

    On May 10, 1993, nearly 100 representatives of the major defense companies, federal agencies, national laboratories, universities, and state governments met at the U.S. Department of Trans;pportation's Volpe National Transportation Systems Center, Ca...

  17. Sex steroid hormones and sex hormone binding globulin levels, CYP17 MSP AI (-34T:C) and CYP19 codon 39 (Trp:Arg) variants in children with developmental stuttering.

    Science.gov (United States)

    Mohammadi, Hiwa; Joghataei, Mohammad Taghi; Rahimi, Zohreh; Faghihi, Faezeh; Khazaie, Habibolah; Farhangdoost, Hashem; Mehrpour, Masoud

    2017-12-01

    Developmental stuttering is known to be a sexually dimorphic and male-biased speech motor control disorder. In the present case-control study, we investigated the relationship between developmental stuttering and steroid hormones. Serum levels of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), oestradiol, progesterone, cortisol, and sex hormone binding globulin (SHBG), as well as the 2nd/4th digit ratio (2D:4D), an indicator of prenatal testosterone level, were compared between children who stutter (CWS) and children who do not stutter (CWNS). Moreover, two SNPs (CYP17 -34 T:C (MSP AI) and CYP19 T:C (Trp:Arg)) of cytochrome P450, which is involved in steroid metabolism pathways, were analysed between the groups. Our results showed significantly higher levels of testosterone, DHT, and oestradiol in CWS in comparison with CWNS. The severity of stuttering was positively correlated with the serum levels of testosterone, DHEA, and cortisol, whereas no association was seen between the stuttering and digit ratio, progesterone, or SHBG. The CYP17CC genotype was significantly associated with the disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Parallel studies of His-DTrp-Ala-Trp-DPhe-Lys-NH2 and human pancreatic growth hormone-releasing factor-44-NH2 in rat primary pituitary cell monolayer culture.

    Science.gov (United States)

    Sartor, O; Bowers, C Y; Chang, D

    1985-03-01

    His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GH-RP-6) is a synthetic hexapeptide that specifically releases GH both in vivo and in vitro in pituitary incubates. In this study, for the first time, GH-RP-6 was studied in primary pituitary cell monolayer culture. Parallel studies were performed with human pancreatic GH-releasing factor-44 (hpGRF-44). Culture conditions optimal for GH-RP-6 were not optimal for hpGRF-44. Both peptides released GH in a dose- and time-dependent manner. In this assay system, the ED50 for GH-RP-6 was 9 nM, and the ED50 for hp-GRF-44 was 1.6 nM. Calcium-blocking agents inhibited the GH responses of both peptides as well as basal GH release. Pretreatment with GH-RP-6 decreased the subsequent response to both GH-RP-6 and hpGRF-44. hpGRF-44 down regulated itself but not GH-RP-6. Rat sera potentiated the GH response of hpGRF-44 but not that of GH-RP-6. GH-RP-6 and hpGRF-44 GH responses were additive. These results suggest that GH-RP-6 and hpGRF-44 stimulate GH release via different somatotroph receptors.

  19. Project Exodus

    Science.gov (United States)

    1990-01-01

    Project Exodus is an in-depth study to identify and address the basic problems of a manned mission to Mars. The most important problems concern propulsion, life support, structure, trajectory, and finance. Exodus will employ a passenger ship, cargo ship, and landing craft for the journey to Mars. These three major components of the mission design are discussed separately. Within each component the design characteristics of structures, trajectory, and propulsion are addressed. The design characteristics of life support are mentioned only in those sections requiring it.

  20. CAREM Project

    International Nuclear Information System (INIS)

    Ishida, Viviana; Gomez, Silvia

    2001-01-01

    CAREM project consists on the development and design of an advanced nuclear power plant. CAREM is a very low power innovative reactor conceived with new generation design solutions. Based on an indirect cycle integrated light water reactor using enriched uranium, CAREM has some distinctive features that greatly simplify the reactor and also contribute to a high level of safety: integrated primary system, primary system cooling by natural convection, self pressurization, and passive safety systems. In order to verify its innovative features the construction of a prototype is planned. (author)

  1. PORTNUS Project

    Energy Technology Data Exchange (ETDEWEB)

    Loyal, Rebecca E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-07-14

    The objective of the Portunus Project is to create large, automated offshore ports that will the pace and scale of international trade. Additionally, these ports would increase the number of U.S. domestic trade vessels needed, as the imported goods would need to be transported from these offshore platforms to land-based ports such as Boston, Los Angeles, and Newark. Currently, domestic trade in the United States can only be conducted by vessels that abide by the Merchant Marine Act of 1920 – also referred to as the Jones Act. The Jones Act stipulates that vessels involved in domestic trade must be U.S. owned, U.S. built, and manned by a crew made up of U.S. citizens. The Portunus Project would increase the number of Jones Act vessels needed, which raises an interesting economic concern. Are Jones Act ships more expensive to operate than foreign vessels? Would it be more economically efficient to modify the Jones Act and allow vessels manned by foreign crews to engage in U.S. domestic trade? While opposition to altering the Jones Act is strong, it is important to consider the possibility that ship-owners who employ foreign crews will lobby for the chance to enter a growing domestic trade market. Their success would mean potential job loss for thousands of Americans currently employed in maritime trade.

  2. FLORAM project

    Energy Technology Data Exchange (ETDEWEB)

    Zulauf, W E [Sao Paolos Environmental Secretariat, Sao Paolo (Brazil); Goelho, A S.R. [Riocell, S.A. (Brazil); Saber, A [IEA-Instituto de Estudos Avancados (Brazil); and others

    1996-12-31

    The project FLORAM was formulated at the `Institute for Advanced Studies` of the University of Sao Paulo. It aims at decreasing the level of carbon dioxide in the atmosphere and thus curbing the green-house effect by way of a huge effort of forestation and reforestation. The resulting forests when the trees mature, will be responsible for the absorption of about 6 billion tons of excess carbon. It represents 5 % of the total amount of CO{sub 2} which is in excess in the earth`s atmosphere and represents 5 % of the available continental surfaces which can be forested as well. Therefore, if similar projects are implemented throughout the world, in theory all the exceeding CO{sub 2}, responsible for the `greenhouse effect`, (27 % or 115 billion tons of carbon) would be absorbed. Regarding this fact, there would be a 400 million hectar increase of growing forests. FLORAM in Brazil aims to plant 20.000.000 ha in 2 years at a cost of 20 billion dollars. If it reaches its goals that will mean that Brazil will have reforested an area almost half as big as France. (author)

  3. FLORAM project

    Energy Technology Data Exchange (ETDEWEB)

    Zulauf, W.E. [Sao Paolos Environmental Secretariat, Sao Paolo (Brazil); Goelho, A.S.R. [Riocell, S.A. (Brazil); Saber, A. [IEA-Instituto de Estudos Avancados (Brazil)] [and others

    1995-12-31

    The project FLORAM was formulated at the `Institute for Advanced Studies` of the University of Sao Paulo. It aims at decreasing the level of carbon dioxide in the atmosphere and thus curbing the green-house effect by way of a huge effort of forestation and reforestation. The resulting forests when the trees mature, will be responsible for the absorption of about 6 billion tons of excess carbon. It represents 5 % of the total amount of CO{sub 2} which is in excess in the earth`s atmosphere and represents 5 % of the available continental surfaces which can be forested as well. Therefore, if similar projects are implemented throughout the world, in theory all the exceeding CO{sub 2}, responsible for the `greenhouse effect`, (27 % or 115 billion tons of carbon) would be absorbed. Regarding this fact, there would be a 400 million hectar increase of growing forests. FLORAM in Brazil aims to plant 20.000.000 ha in 2 years at a cost of 20 billion dollars. If it reaches its goals that will mean that Brazil will have reforested an area almost half as big as France. (author)

  4. SISCAL project

    Science.gov (United States)

    Santer, Richard P.; Fell, Frank

    2003-05-01

    The first "ocean colour" sensor, Coastal Zone Color Scanner (CZCS), was launched in 1978. Oceanographers learnt a lot from CZCS but it remained a purely scientific sensor. In recent years, a new generation of satellite-borne earth observation (EO) instruments has been brought into space. These instruments combine high spectral and spatial resolution with revisiting rates of the order of one per day. More instruments with further increased spatial, spectral and temporal resolution will be available within the next years. In the meantime, evaluation procedures taking advantage of the capabilities of the new instruments were derived, allowing the retrieval of ecologically important parameters with higher accuracy than before. Space agencies are now able to collect and to process satellite data in real time and to disseminate them via the Internet. It is therefore meanwhile possible to envisage using EO operationally. In principle, a significant demand for EO data products on terrestrial or marine ecosystems exists both with public authorities (environmental protection, emergency management, natural resources management, national parks, regional planning, etc) and private companies (tourist industry, insurance companies, water suppliers, etc). However, for a number of reasons, many data products that can be derived from the new instruments and methods have not yet left the scientific community towards public or private end users. It is the intention of the proposed SISCAL (Satellite-based Information System on Coastal Areas and Lakes) project to contribute to the closure of the existing gap between space agencies and research institutions on one side and end users on the other side. To do so, we intend to create a data processor that automatically derives and subsequently delivers over the Internet, in Near-Real-Time (NRT), a number of data products tailored to individual end user needs. The data products will be generated using a Geographical Information System (GIS

  5. Enhancing cancer registry data for comparative effectiveness research (CER) project: overview and methodology.

    Science.gov (United States)

    Chen, Vivien W; Eheman, Christie R; Johnson, Christopher J; Hernandez, Monique N; Rousseau, David; Styles, Timothy S; West, Dee W; Hsieh, Meichin; Hakenewerth, Anne M; Celaya, Maria O; Rycroft, Randi K; Wike, Jennifer M; Pearson, Melissa; Brockhouse, Judy; Mulvihill, Linda G; Zhang, Kevin B

    2014-01-01

    Following the Institute of Medicine's 2009 report on the national priorities for comparative effectiveness research (CER), funding for support of CER became available in 2009 through the American Recovery and Re-investment Act. The Centers for Disease Control and Prevention (CDC) received funding to enhance the infrastructure of population-based cancer registries and to expand registry data collection to support CER. The CDC established 10 specialized registries within the National Program of Cancer Registries (NPCR) to enhance data collection for all cancers and to address targeted CER questions, including the clinical use and prognostic value of specific biomarkers. The project also included a special focus on detailed first course of treatment for cancers of the breast, colon, and rectum, as well as chronic myeloid leukemia (CML) diagnosed in 2011. This paper describes the methodology and the work conducted by the CDC and the NPCR specialized registries in collecting data for the 4 special focused cancers, including the selection of additional data variables, development of data collection tools and software modifications, institutional review board approvals, training, collection of detailed first course of treatment, and quality assurance. It also presents the characteristics of the study population and discusses the strengths and limitations of using population-based cancer registries to support CER as well as the potential future role of population-based cancer registries in assessing the quality of patient care and cancer control.

  6. Correction: β-Amyrin synthase from Euphorbia tirucalli L. functional analyses of the highly conserved aromatic residues Phe413, Tyr259 and Trp257 disclose the importance of the appropriate steric bulk, and cation-π and CH-π interactions for the efficient catalytic action of the polyolefin cyclization cascade.

    Science.gov (United States)

    Ito, Ryousuke; Nakada, Chika; Hoshino, Tsutomu

    2017-01-18

    Correction for 'β-Amyrin synthase from Euphorbia tirucalli L. functional analyses of the highly conserved aromatic residues Phe413, Tyr259 and Trp257 disclose the importance of the appropriate steric bulk, and cation-π and CH-π interactions for the efficient catalytic action of the polyolefin cyclization cascade' by Ryousuke Ito et al., Org. Biomol. Chem., 2017, 15, 177-188.

  7. Project Financing

    OpenAIRE

    S. GATTI

    2005-01-01

    Στην εισαγωγή της παρούσας εργασίας δίνεται ο ορισμός του project financing, τα ιστορικά στοιχεία και οι τάσεις αγοράς του. Στο πρώτο κεφάλαιο αναφέρεται γιατί οι εταιρείες προτιμούν την χρηματοδότηση με project financing. Γίνεται λόγος για τα πλεονεκτήματά του έναντι της άμεσης χρηματοδότησης, καθώς και για τα μειονεκτήματα του project financing. Στο δεύτερο κεφάλαιο παρουσιάζονται τα χρηματοοικονομικά στοιχεία και ο ρόλος του χρηματοοικονομικού συμβούλου. Στην τρίτη ενότητα γίνεται η αναγνώ...

  8. Project: Ultracentrifuges

    International Nuclear Information System (INIS)

    Olea C, O.

    1990-07-01

    The trans elastic ultracentrifuge of magnetic suspension, is an instrument that arose of an interdisciplinary group directed by the Dr. James Clark Keith where it was projected, designed and built a centrifuge that didn't exist, to be applied in forced diffusion of uranium, like one of the many application fields. The written present, has as purpose to give to know the fundamental physical principles of this technology, its fundamental characteristics of design, the application of this in the separation process of isotopes, as well as the previous studies and essential control parameters in the experimental processes, the same thing that, the most outstanding results and the detection systems used in the confirmation and finally, the carried out potential applications of the principles of the ultracentrifugation technology. (Author)

  9. ENVISION Project

    CERN Multimedia

    Ballantine, A; Dixon-Altaber, H; Dosanjh, M; Kuchina, L

    2011-01-01

    Hadrontherapy is a highly advanced technique of cancer radiotherapy that uses beams of charged particles (ions) to destroy tumour cells. While conventional X-rays traverse the human body depositing radiation as they pass through, ions deliver most of their energy at one point. Hadrontherapy is most advantageous once the position of the tumour is accurately known, so that healthy tissues can be protected. Accurate positioning is a crucial challenge for targeting moving organs, as in lung cancer, and for adapting the irradiation as the tumour shrinks with treatment. Therefore, quality assurance becomes one of the most relevant issues for an effective outcome of the cancer treatment. In order to improve the quality assurance tools for hadrontherapy, the European Commission is funding ENVISION, a 4-year project that aims at developing solutions for: real-• time non invasive monitoring • quantitative imaging • precise determination of delivered dose • fast feedback for optimal treatment planning • real-t...

  10. EUROTRAC projects

    International Nuclear Information System (INIS)

    Slanina, J.; Arends, B.G.; Wyers, G.P.

    1992-07-01

    The projects discussed are BIATEX (BIosphere-ATmosphere EXchange of pollutants), ACE (Acidity in Clouds Experiment) and GCE (Ground-based Cloud Experiment). ECN also coordinates BIATEX and contributes to the coordination of EUROTRAC. Research in BIATEX is aimed at the development of equipment, by which atmosphere-surface interactions of air pollution can be quantified. A ion chromatograph, connected to a rotating denuder, is developed to be applicated in the field for on-line analysis of denuder extracts and other samples. To investigate dry deposition of ammonia a continuous-flow denuder has been developed. A thermodenuder system to measure the concentrations of HNO 3 and NH 4 NO 3 in the ambient air is optimized to determine depositions and is part of the ECN monitoring station in Zegveld, Netherlands. An aerosol separation technique, based on a cyclone separator, has also been developed. All this equipment has been used in field experiments above wheat and heather. An automated monitoring station for long-term investigations of NH 3 , HNO 3 and SO 2 dry deposition on grassland and the impact of the deposition on the presence and composition of water films has been set up and fully tested. Research in GCE concerns the uptake and conversion of air pollution in clouds (cloud chemistry). Measuring equipment from several collaborative institutes has been specified and calibrated in a cloud chamber at ECN. The ECN contribution is the determination of the gas phase composition and the micro-physical characterization of the clouds. Measurement campaigns were carried out in the Po area (Italy) in fog, and in Kleiner Feldberg near Frankfurt, Germany, in orographic clouds. Estimations are given of the deposition of fog water and cloud water on forests in the Netherlands and the low mountain range in Germany. The project ACE was not started because of financial reasons and will be reconsidered. 26 figs., 1 tab., 3 apps., 34 refs

  11. Northern California CO2 Reduction Project

    Energy Technology Data Exchange (ETDEWEB)

    Hymes, Edward [C6 Resources LLC, Houston, TX (United States)

    2010-06-16

    C6 Resources LLC, a wholly owned subsidiary of Shell Oil Company, worked with the US Department of Energy (DOE) under a Cooperative Agreement to develop the Northern California CO2 Reduction Project. The objective of the Project is to demonstrate the viability of using Carbon Capture and Sequestration (CCS) to reduce existing greenhouse gas emissions from industrial sources on a large-scale. The Project will capture more than 700,000 metric tonnes of CO2 per year, which is currently being vented to the atmosphere from the Shell Martinez Refinery in Contra Costa County. The CO2 will be compressed and dehydrated at the refinery and then transported via pipeline to a sequestration site in a rural area in neighboring Solano County. The CO2 will be sequestered into a deep saline formation (more than two miles underground) and will be monitored to assure secure, long-term containment. The pipeline will be designed to carry as much as 1,400,000 metric tonnes of CO2 per year, so additional capacity will be available to accommodate CO2 captured from other industrial sources. The Project is expected to begin operation in 2015. The Project has two distinct phases. The overall objective of Phase 1 was to develop a fully definitive design basis for the Project. The Cooperative Agreement with the DOE provided cost sharing for Phase 1 and the opportunity to apply for additional DOE cost sharing for Phase 2, comprising the design, construction and operation of the Project. Phase 1 has been completed. DOE co-funding is provided by the American Recovery and Reinvestment Act (ARRA) of 2009. As prescribed by ARRA, the Project will stimulate the local economy by creating manufacturing, transportation, construction, operations, and management jobs while addressing the need to reduce greenhouse gas emissions at an accelerated pace. The Project, which will also assist in meeting the CO2 reduction requirements set

  12. Project Success in IT Project Management

    OpenAIRE

    Siddiqui, Farhan Ahmed

    2010-01-01

    The rate of failed and challenged Information Technology (IT) projects is too high according to the CHAOS Studies by the Standish Group and the literature on project management (Standish Group, 2008). The CHAOS Studies define project success as meeting the triple constraints of scope, time, and cost. The criteria for project success need to be agreed by all parties before the start of the project and constantly reviewed as the project progresses. Assessing critical success factors is another ...

  13. Evidence of preorganization in quinonoid intermediate formation from L-Trp in H463F mutant Escherichia coli tryptophan indole-lyase from effects of pressure and pH.

    Science.gov (United States)

    Phillips, Robert S; Kalu, Ukoha; Hay, Sam

    2012-08-21

    conclusion that the preorganization of the H463F TIL Trp complex, which is probably dominated by motion of the l-Trp indole moiety of the aldimine complex, contributes to quinonoid intermediate formation.

  14. Project LASER

    Science.gov (United States)

    1990-01-01

    NASA formally launched Project LASER (Learning About Science, Engineering and Research) in March 1990, a program designed to help teachers improve science and mathematics education and to provide 'hands on' experiences. It featured the first LASER Mobile Teacher Resource Center (MTRC), is designed to reach educators all over the nation. NASA hopes to operate several MTRCs with funds provided by private industry. The mobile unit is a 22-ton tractor-trailer stocked with NASA educational publications and outfitted with six work stations. Each work station, which can accommodate two teachers at a time, has a computer providing access to NASA Spacelink. Each also has video recorders and photocopy/photographic equipment for the teacher's use. MTRC is only one of the five major elements within LASER. The others are: a Space Technology Course, to promote integration of space science studies with traditional courses; the Volunteer Databank, in which NASA employees are encouraged to volunteer as tutors, instructors, etc; Mobile Discovery Laboratories that will carry simple laboratory equipment and computers to provide hands-on activities for students and demonstrations of classroom activities for teachers; and the Public Library Science Program which will present library based science and math programs.

  15. Project Longshot

    Science.gov (United States)

    West, J. Curtis; Chamberlain, Sally A.; Stevens, Robert; Pagan, Neftali

    1989-01-01

    Project Longshot is an unmanned probe to our nearest star system, Alpha Centauri, 4.3 light years away. The Centauri system is a trinary system consisting of two central stars (A and B) orbiting a barycenter, and a third (Proxima Centauri) orbiting the two. The system is a declination of -67 degrees. The goal is to reach the Centauri system in 50 years. This time space was chosen because any shorter time would be impossible of the relativistic velocities involved, and any greater time would be impossible because of the difficulty of creating a spacecraft with such a long lifetime. Therefore, the following mission profile is proposed: (1) spacecraft is assembled in Earth orbit; (2) spacecraft escapes Earth and Sun in the ecliptic with a single impulse maneuver; (3) spacecraft changed declination to point toward Centauri system; (4) spacecraft accelerates to 0.1c; (5) spacecraft coasts at 0.1c for 41 years; (6) spacecraft decelerates upon reaching Centauri system; and (7) spacecraft orbits Centauri system, conducts investigations, and relays data to Earth. The total time to reach the Centauri system, taking into consideration acceleration and deceleration, will be approximately 50 years.

  16. Evolution of the U.S. Energy Service Company Industry: Market Size and Project Performance from 1990-2008

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, Peter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Goldman, Charles A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Satchwell, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2012-05-08

    The U.S. energy service company (ESCO) industry is an example of a private sector business model where energy savings are delivered to customers primarily through the use of performance-based contracts. This study was conceived as a snapshot of the ESCO industry prior to the economic slowdown and the introduction of federal stimulus funding mandated by enactment of the American Recovery and Reinvestment Act of 2009 (ARRA). This study utilizes two parallel analytic approaches to characterize ESCO industry and market trends in the U.S.: (1) a “top-down” approach involving a survey of individual ESCOs to estimate aggregate industry activity and (2) a “bottom-up” analysis of a database of -3,265 projects (representing over $8B in project investment) that reports market trends including installed EE retrofit strategies, project installation costs and savings, project payback times, and benefit-cost ratios over time. Despite the onset of an economic recession, the U.S. ESCO industry managed to grow at about 7% per year between 2006 and 2008. ESCO industry revenues are relatively small compared to total U.S. energy expenditures (about $4.1 billion in 2008), but ESCOs anticipated accelerated growth through 2011 (25% per year). We found that 2,484 ESCO projects in our database generated -$4.0 billion ($2009) in net, direct economic benefits to their customers. We estimate that the ESCO project database includes about 20% of all U.S. ESCO market activity from 1990-2008. Assuming the net benefits per project are comparable for ESCO projects that are not included in the LBNL database, this would suggest that the ESCO industry has generated -$23 billion in net direct economic benefits for customers at projects installed between 1990 and 2008. We found that nearly 85% of all public and institutional projects met or exceeded the guaranteed level of savings. We estimated that a typical ESCO project generated $1.5 dollars of direct benefits for every dollar of customer

  17. ConocoPhillips Sweeny IGCC/CCS Project

    Energy Technology Data Exchange (ETDEWEB)

    Paul Talarico; Charles Sugg; Thomas Hren; Lauri Branch; Joseph Garcia; Alan Rezigh; Michelle Pittenger; Kathleen Bower; Jonathan Philley; Michael Culligan; Jeremy Maslen; Michele Woods; Kevin Elm

    2010-06-16

    Under its Industrial Carbon Capture and Sequestration (ICCS) Program, the United States (U.S.) Department of Energy (DOE) selected ConocoPhillips Company (ConocoPhillips) to receive funding through the American Recovery and Reinvestment Act (ARRA) of 2009 for the proposed Sweeny Integrated Gasification Combined Cycle (IGCC)/Carbon Capture and Storage (CCS) Project (Project) to be located in Brazoria County, Texas. Under the program, the DOE is partnering with industry to demonstrate the commercial viability and operational readiness of technologies that would capture carbon dioxide (CO{sub 2}) emissions from industrial sources and either sequester those emissions, or beneficially reuse them. The primary objective of the proposed Project was to demonstrate the efficacy of advanced technologies that capture CO{sub 2} from a large industrial source and store the CO{sub 2} in underground formations, while achieving a successful business venture for the entity (entities) involved. The Project would capture 85% of the CO{sub 2} produced from a petroleum coke (petcoke) fed, 703 MWnet (1,000 MWgross) IGCC power plant, using the ConocoPhillips (COP) proprietary and commercially proven E-Gas{trademark} gasification technology, at the existing 247,000 barrel per day COP Sweeny Refinery. In addition, a number of other commercially available technologies would be integrated into a conventional IGCC Plant in a unique, efficient, and reliable design that would capture CO{sub 2}. The primary destination for the CO{sub 2} would be a depleted natural gas field suitable for CO{sub 2} storage ('Storage Facility'). COP would also develop commercial options to sell a portion of the IGCC Plant's CO{sub 2} output to the growing Gulf Coast enhanced oil recovery (EOR) market. The IGCC Plant would produce electric power for sale in the Electric Reliability Council of Texas Houston Zone. The existing refinery effluent water would be treated and reused to fulfill all process

  18. Novel Antimicrobial Peptides EeCentrocins 1, 2 and EeStrongylocin 2 from the Edible Sea Urchin Echinus esculentus Have 6-Br-Trp Post-Translational Modifications.

    Directory of Open Access Journals (Sweden)

    Runar Gjerp Solstad

    Full Text Available The global problem of microbial resistance to antibiotics has resulted in an urgent need to develop new antimicrobial agents. Natural antimicrobial peptides are considered promising candidates for drug development. Echinoderms, which rely on innate immunity factors in the defence against harmful microorganisms, are sources of novel antimicrobial peptides. This study aimed to isolate and characterise antimicrobial peptides from the Edible sea urchin Echinus esculentus. Using bioassay-guided purification and cDNA cloning, three antimicrobial peptides were characterised from the haemocytes of the sea urchin; two heterodimeric peptides and a cysteine-rich peptide. The peptides were named EeCentrocin 1 and 2 and EeStrongylocin 2, respectively, due to their apparent homology to the published centrocins and strongylocins isolated from the green sea urchin Strongylocentrotus droebachiensis. The two centrocin-like peptides EeCentrocin 1 and 2 are intramolecularly connected via a disulphide bond to form a heterodimeric structure, containing a cationic heavy chain of 30 and 32 amino acids and a light chain of 13 amino acids. Additionally, the light chain of EeCentrocin 2 seems to be N-terminally blocked by a pyroglutamic acid residue. The heavy chains of EeCentrocins 1 and 2 were synthesised and shown to be responsible for the antimicrobial activity of the natural peptides. EeStrongylocin 2 contains 6 cysteines engaged in 3 disulphide bonds. A fourth peptide (Ee4635 was also discovered but not fully characterised. Using mass spectrometric and NMR analyses, EeCentrocins 1 and 2, EeStrongylocin 2 and Ee4635 were all shown to contain post-translationally brominated Trp residues in the 6 position of the indole ring.

  19. The Arg59Trp variant in ANGPTL8 (betatrophin) is associated with total and HDL-cholesterol in American Indians and Mexican Americans and differentially affects cleavage of ANGPTL3.

    Science.gov (United States)

    Hanson, Robert L; Leti, Fatjon; Tsinajinnie, Darwin; Kobes, Sayuko; Puppala, Sobha; Curran, Joanne E; Almasy, Laura; Lehman, Donna M; Blangero, John; Duggirala, Ravindranath; DiStefano, Johanna K

    2016-06-01

    We previously identified a locus linked to total cholesterol (TC) concentration in Pima Indians on chromosome 19p. To characterize this locus, we genotyped >2000 SNPs in 1838 Pimas and assessed association with log(TC). We observed evidence for association with log(TC) with rs2278426 (3.5% decrease/copy of the T allele; P=5.045×10(-6)) in the ANGPTL8 (angiopoietin-like 8) gene. We replicated this association in 2413 participants of the San Antonio Mexican American Family Study (SAMAFS: 2.0% decrease per copy of the T allele; P=0.005842). In a meta-analysis of the combined data, we found the strongest estimated effect with rs2278426 (P=2.563×10(-7)). The variant T allele at rs2278426 predicts an Arg59Trp substitution and has previously been associated with LDL-C and HDL-C. In Pimas and SAMAFS participants, the T allele of rs2278426 was associated with reduced HDL-C levels (P=0.000741 and 0.00002, respectively), and the combined estimated effect for the two cohorts was -3.8% (P=8.526×10(-8)). ANGPTL8 transcript and protein levels increased in response to both glucose and insulin. The variant allele was associated with increased levels of cleaved ANGPTL3. We conclude that individuals with the variant allele may have lower TC and HDL-C levels due to increased activation of ANGPTL3 by ANGPTL8. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. GENETIC VARIATION IN THE BETA-3-ADRENORECEPTOR GENE (TRP64ARG POLYMORPHISM) AND THEIR INFLUENCE ON ANTHROPOMETRIC PARAMETERS AND INSULIN RESISTANCE AFTER A HIGH PROTEIN/LOW CARBOHYDRATE VERSUS A STANDARD HYPOCALORIC DIET.

    Science.gov (United States)

    de Luis, Daniel Antonio; Aller, Rocío; Izaola, Olatz; de la Fuente, Beatriz; Romero, Enrique

    2015-08-01

    the Trp64Arg variant in Beta receptor has been reported to be associated with increased body weight and insulin resistance Objective: the aim of our study was to investigate the influence of polymorphism (rs 4994) in Beta-3-adrenergic receptor gene on metabolic response and weight loss in a medium-term intervention study secondary's to a high protein/low carbohydrate vs. a standard hypocaloric diets (1000 kcal/day). a population of 284 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 9-month period in which subjects received 1 of 2 diets (diet HP: high protein/low carbohydrate vs diet S: standard diet). there were no significant differences between the positive effects (on weight, BMI, waist circumference, fat mass, systolic blood pressure and leptin levels) in either genotype group with both diets. With both diets and only in wild genotype (diet HP vs diet S), total cholesterol (-10.1 ± 3.9 mg/dl vs -10.1 ± 2.2 mg/dl;p>0.05), LDL cholesterol (-9.5 ± 2.1 mg/dl vs -8.5 ± 2.3 mg/dl;p>0.05) and triglycerides (-19.1 ± 2.1 mg/dl vs -14.3 ± 2.1 mg/dl;p>0.05) decreased. The improvement in these parameters was similar in subjects with diet HP than HS. With diet HP and only in wild genotype, insulin levels (-3.7 ± 1.9 UI/L;phypocaloric diets is the greatest in subjects with normal homozygous beta 3-AR gene. Improvement in total cholesterol, LDL-cholesterol, triglyceride, glucose, insulin and HOMA-R levels is better than in the heterozygous group. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  1. /sup 3/H)-(H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2) ((/sup 3/H)CTOP), a potent and highly selective peptide for mu opioid receptors in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Hawkins, K.N.; Knapp, R.J.; Lui, G.K.; Gulya, K.; Kazmierski, W.; Wan, Y.P.; Pelton, J.T.; Hruby, V.J.; Yamamura, H.I.

    1989-01-01

    The cyclic, conformationally restricted octapeptide (3H)-(H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2) ((3H)CTOP) was synthesized and its binding to mu opioid receptors was characterized in rat brain membrane preparations. Association rates (k+1) of 1.25 x 10(8) M-1 min-1 and 2.49 x 10(8) M-1 min-1 at 25 and 37 degrees C, respectively, were obtained, whereas dissociation rates (k-1) at the same temperatures were 1.93 x 10(-2) min-1 and 1.03 x 10(-1) min-1 at 25 and 37 degrees C, respectively. Saturation isotherms of (3H)CTOP binding to rat brain membranes gave apparent Kd values of 0.16 and 0.41 nM at 25 and 37 degrees C, respectively. Maximal number of binding sites in rat brain membranes were found to be 94 and 81 fmol/mg of protein at 25 and 37 degrees C, respectively. (3H)CTOP binding over a concentration range of 0.1 to 10 nM was best fit by a one site model consistent with binding to a single site. The general effect of different metal ions and guanyl-5'-yl-imidodiphosphate on (3H)CTOP binding was to reduce its affinity. High concentrations (100 mM) of sodium also produced a reduction of the apparent mu receptor density. Utilizing the delta opioid receptor specific peptide (3H)-(D-Pen2,D-Pen5)enkephalin, CTOP appeared to be about 2000-fold more specific for mu vs. delta opioid receptor than naloxone. Specific (3H)CTOP binding was inhibited by a large number of opioid or opiate ligands.

  2. Biological evaluation of 177Lu-labeled DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 for gastrin-releasing peptide receptor-positive prostate tumor targeting

    International Nuclear Information System (INIS)

    Lim, Jae Cheong; Cho, Eun Ha; Kim, Jin Joo; Choi, Sang Mu; Lee, So young; Nam, Sung Soo; Park, Ul Jae; Park, Soo Hyun

    2015-01-01

    Bombesin binds with selectivity and high affinity to a Gastrin-releasing peptide receptor (GRPR), which is highly overexpressed in prostate cancer cells. The present study describes the in vitro and in vivo biological characteristics of DOTA-Ala(SO 3 H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH 2 (DOTA-sBBNA), an antagonist analogue of bombesin peptide for the targeting of GRPR. DOTA-sBBNA was synthesized and labeled with 177 Lu as previously published. A saturation assay on PC-3 human prostate cancer cells revealed that the Kd value of the radiolabeled peptide was 1.88 nM with a maximum binding capacity (Bmax) of 289.3 fmol/10 6 cells. The radio-peptide slowly internalized, and 24.4 ± 0.5% of the total binding was internalized in 4 hr. Biodistribution studies were conducted in healthy and PC-3 xenografted balb/c mice, which showed high uptake and retention of tumor-associated radioactivity in PC-3 xenografted mice. The tumor-to-blood ratio was 126.02 ± 9.36 at 1.5 hr p.i., and was increased to 216.33 ± 61.58 at 24 hr p.i., which means that the radiolabeled peptide was highly accumulated in a tumor and rapidly cleared from the blood pool. The GRPR is also over-expressed in Korean prostate cancer patients. These results suggest that this 177 Lu-labeled peptide has promising characteristics for application in nuclear medicine, namely for the diagnosis and treatment of GRPR over-expressing prostate tumors

  3. Specific Function of the Met-Tyr-Trp Adduct Radical and Residues Arg-418 and Asp-137 in the Atypical Catalase Reaction of Catalase-Peroxidase KatG*

    Science.gov (United States)

    Zhao, Xiangbo; Khajo, Abdelahad; Jarrett, Sanchez; Suarez, Javier; Levitsky, Yan; Burger, Richard M.; Jarzecki, Andrzej A.; Magliozzo, Richard S.

    2012-01-01

    Catalase activity of the dual-function heme enzyme catalase-peroxidase (KatG) depends on several structural elements, including a unique adduct formed from covalently linked side chains of three conserved amino acids (Met-255, Tyr-229, and Trp-107, Mycobacterium tuberculosis KatG numbering) (MYW). Mutagenesis, electron paramagnetic resonance, and optical stopped-flow experiments, along with calculations using density functional theory (DFT) methods revealed the basis of the requirement for a radical on the MYW-adduct, for oxyferrous heme, and for conserved residues Arg-418 and Asp-137 in the rapid catalase reaction. The participation of an oxyferrous heme intermediate (dioxyheme) throughout the pH range of catalase activity is suggested from our finding that carbon monoxide inhibits the activity at both acidic and alkaline pH. In the presence of H2O2, the MYW-adduct radical is formed normally in KatG[D137S] but this mutant is defective in forming dioxyheme and lacks catalase activity. KatG[R418L] is also catalase deficient but exhibits normal formation of the adduct radical and dioxyheme. Both mutants exhibit a coincidence between MYW-adduct radical persistence and H2O2 consumption as a function of time, and enhanced subunit oligomerization during turnover, suggesting that the two mutations disrupting catalase turnover allow increased migration of the MYW-adduct radical to protein surface residues. DFT calculations showed that an interaction between the side chain of residue Arg-418 and Tyr-229 in the MYW-adduct radical favors reaction of the radical with the adjacent dioxyheme intermediate present throughout turnover in WT KatG. Release of molecular oxygen and regeneration of resting enzyme are thereby catalyzed in the last step of a proposed catalase reaction. PMID:22918833

  4. Project Success in Agile Development Software Projects

    Science.gov (United States)

    Farlik, John T.

    2016-01-01

    Project success has multiple definitions in the scholarly literature. Research has shown that some scholars and practitioners define project success as the completion of a project within schedule and within budget. Others consider a successful project as one in which the customer is satisfied with the product. This quantitative study was conducted…

  5. Ace Project as a Project Management Tool

    Science.gov (United States)

    Cline, Melinda; Guynes, Carl S.; Simard, Karine

    2010-01-01

    The primary challenge of project management is to achieve the project goals and objectives while adhering to project constraints--usually scope, quality, time and budget. The secondary challenge is to optimize the allocation and integration of resources necessary to meet pre-defined objectives. Project management software provides an active…

  6. Organizations, projects and culture

    NARCIS (Netherlands)

    J. van Cleeff; Pieter van Nispen tot Pannerden

    2016-01-01

    Purpose: to explore and demonstrate the effects of organizational culture on projects, in particular project culture and project management style. Methodology/approach: descriptive and explorative; through students’ groups. Findings: the cultural relationship between organizations, their projects

  7. Colorado Better Buildings Project. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Strife, Susie [Boulder County, Boulder, CO (United States); Yancey, Lea [Boulder County, Boulder, CO (United States)

    2013-12-30

    The Colorado Better Buildings project intended to bring new and existing energy efficiency model programs to market with regional collaboration and funding partnerships. The goals for Boulder County and its program partners were to advance energy efficiency investments, stimulate economic growth in Colorado and advance the state’s energy independence. Collectively, three counties set out to complete 9,025 energy efficiency upgrades in 2.5 years and they succeeded in doing so. Energy efficiency upgrades have been completed in more than 11,000 homes and businesses in these communities. Boulder County and its partners received a $25 million BetterBuildings grant from the U.S. Department of Energy under the American Recovery and Reinvestment Act in the summer of 2010. This was also known as the Energy Efficiency and Conservation Block Grants program. With this funding, Boulder County, the City and County of Denver, and Garfield County set out to design programs for the residential and commercial sectors to overcome key barriers in the energy upgrade process. Since January 2011, these communities have paired homeowners and business owners with an Energy Advisor – an expert to help move from assessment to upgrade with minimal hassle. Pairing this step-by-step assistance with financing incentives has effectively addressed many key barriers, resulting in energy efficiency improvements and happy customers. An expert energy advisor guides the building owner through every step of the process, coordinating the energy assessment, interpreting results for a customized action plan, providing a list of contractors, and finding and applying for all available rebates and low-interest loans. In addition to the expert advising and financial incentives, the programs also included elements of social marketing, technical assistance, workforce development and contractor trainings, project monitoring and verification, and a cloud-based customer data system to coordinate among field

  8. Evaluation of Project Achievements in VOMARE -project

    OpenAIRE

    Kokkarinen, Eeva

    2011-01-01

    The purpose of the thesis is to study the achievements of VOMARE –project from the Finnish Lifeboat Institutions perspective. The organisation is a roof organisation for voluntary maritime rescue operation in Finland. The Finnish Lifeboat Institution is a lead partner in VOMARE –project which is EU funded project and the aim of the project is to start voluntary rescue operations in Estonia. The theoretical part of the work is divided into two main categories; project management and planni...

  9. A Practical and Robust Execution Time-Frame Procedure for the Multi-Mode Resource-Constrained Project Scheduling Problem with Minimal and Maximal Time Lags

    Directory of Open Access Journals (Sweden)

    Angela Hsiang-Ling Chen

    2016-09-01

    Full Text Available Modeling and optimizing organizational processes, such as the one represented by the Resource-Constrained Project Scheduling Problem (RCPSP, improve outcomes. Based on assumptions and simplification, this model tackles the allocation of resources so that organizations can continue to generate profits and reinvest in future growth. Nonetheless, despite all of the research dedicated to solving the RCPSP and its multi-mode variations, there is no standardized procedure that can guide project management practitioners in their scheduling tasks. This is mainly because many of the proposed approaches are either based on unrealistic/oversimplified scenarios or they propose solution procedures not easily applicable or even feasible in real-life situations. In this study, we solve a more true-to-life and complex model, Multimode RCPSP with minimal and maximal time lags (MRCPSP/max. The complexity of the model solved is presented, and the practicality of the proposed approach is justified depending on only information that is available for every project regardless of its industrial context. The results confirm that it is possible to determine a robust makespan and to calculate an execution time-frame with gaps lower than 11% between their lower and upper bounds. In addition, in many instances, the solved lower bound obtained was equal to the best-known optimum.

  10. Benefits Analysis of Smart Grid Projects. White paper, 2014-2016

    Energy Technology Data Exchange (ETDEWEB)

    Marnay, Chris [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Liu, Liping [China Southern Grid (China); Yu, JianCheng [State Grid of China (China); Zhang, Dong [State Grid of China (China); Mauzy, Josh [Southern California Edison, CA (United States); Shaffer, Brendan [Univ. of California, Irvine, CA (United States); Dong, XuZhu [China Southern Grid (China); Agate, Will [Philadelphia Industrial Development Corp., Philadelphia, PA (United States); Vitiello, Silvia [European Commission, Ispra (Italy). Joint Research Centre; Karali, Nihan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Liu, Angela Xu [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); He, Gang [Stony Brook Univ., NY (United States); Zhao, Li [Univ. of California, Irvine, CA (United States); Zhu, Aimee Limingming [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-11-01

    Smart grids are rolling out internationally, with the United States (U.S.) nearing completion of a significant USD4-plus-billion federal program funded under the American Recovery and Reinvestment Act (ARRA-2009). The emergence of smart grids is widespread across developed countries. Multiple approaches to analyzing the benefits of smart grids have emerged. The goals of this white paper are to review these approaches and analyze examples of each to highlight their differences, advantages, and disadvantages. This work was conducted under the auspices of a joint U.S.-China research effort, the Climate Change Working Group (CCWG) Implementation Plan, Smart Grid. We present comparative benefits assessments (BAs) of smart grid demonstrations in the U.S. and China along with a BA of a pilot project in Europe. In the U.S., we assess projects at two sites: (1) the University of California, Irvine campus (UCI), which consists of two distinct demonstrations: Southern California Edison’s (SCE) Irvine Smart Grid Demonstration Project (ISGD) and the UCI campus itself; and (2) the Navy Yard (TNY) area in Philadelphia, which has been repurposed as a mixed commercial-industrial, and possibly residential, development. In China, we cover several smart-grid aspects of the Sino-Singapore Tianjin Eco-city (TEC) and the Shenzhen Bay Technology and Ecology City (B-TEC). In Europe, we look at a BA of a pilot smart grid project in the Malagrotta area west of Rome, Italy, contributed by the Joint Research Centre (JRC) of the European Commission. The Irvine sub-project BAs use the U.S. Department of Energy (U.S. DOE) Smart Grid Computational Tool (SGCT), which is built on methods developed by the Electric Power Research Institute (EPRI). The TEC sub-project BAs apply Smart Grid Multi-Criteria Analysis (SG-MCA) developed by the State Grid Corporation of China (SGCC) based on the analytic hierarchy process (AHP) with fuzzy logic. The B-TEC and TNY sub-project BAs are evaluated using new

  11. Managing projects using a project management approach

    Directory of Open Access Journals (Sweden)

    Marko D. Andrejić

    2011-04-01

    Full Text Available Modern management theory treats all complex tasks and duties like projects and make these projects possible to be managed by a particular organizational-management concept in order to achieve a goal effectively. A large number of jobs and tasks performed in the system of defense or for defense purposes have the characteristics of projects. Project management is both a skill and a science of monitoring human, material, financial, energy and other resources to achieve required objectives within the given limits: deadlines, time, budget, possibility of realization and the satisfaction of the interests of all project participants. Project management is a traditional area of applied (or functional management focused on managing complex and uncertain situations with defined goals. Introduction In conditions of rapid change and high uncertainty, only adaptive organizations survive, i. e. those that are able not only to react quickly to changes but also to proactively take advantage of changes. Development of project management The biggest influence on the development of the area had complex jobs within the engineering profession. In parallel with the traditional approach new approaches began to develop, while the traditional one still remained in use. Contrary to the traditional engineering approach, a dynamic model first developed in order to respond to demands for greater control of costs. Project management Project management is a skill and knowledge of human and material resources to achieve set objectives within prescribed limits: deadlines, time, budget, possibility of realization, and the satisfaction of all participants in the project. In order to realize a project effectively, it is necessary to manage it rationally. Planning and project management A project plan is a document that allows all team members insight on where to go, when to start and when to arrive, what is necessary to be done in order to achieve the project objectives and what

  12. Sulindac inhibits pancreatic carcinogenesis in LSL-KrasG12D-LSL-Trp53R172H-Pdx-1-Cre mice via suppressing aldo-keto reductase family 1B10 (AKR1B10).

    Science.gov (United States)

    Li, Haonan; Yang, Allison L; Chung, Yeon Tae; Zhang, Wanying; Liao, Jie; Yang, Guang-Yu

    2013-09-01

    Sulindac has been identified as a competitive inhibitor of aldo-keto reductase 1B10 (AKR1B10), an enzyme that plays a key role in carcinogenesis. AKR1B10 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and exhibits lipid substrate specificity, especially for farnesyl and geranylgeranyl. There have been no studies though showing that the inhibition of PDAC by sulindac is via inhibition of AKR1B10, particularly the metabolism of farnesyl/geranylgeranyl and Kras protein prenylation. To determine the chemopreventive effects of sulindac on pancreatic carcinogenesis, 5-week-old LSL-Kras(G12D)-LSL-Trp53(R172H)-Pdx-1-Cre mice (Pan(kras/p53) mice) were fed an AIN93M diet with or without 200 p.p.m. sulindac (n = 20/group). Kaplan-Meier survival analysis showed that average animal survival in Pan(kras/p53) mice was 143.7 ± 8.8 days, and average survival with sulindac was increased to 168.0 ± 8.8 days (P < 0.005). Histopathological analyses revealed that 90% of mice developed PDAC, 10% with metastasis to the liver and lymph nodes. With sulindac, the incidence of PDAC was reduced to 56% (P < 0.01) and only one mouse had lymph node metastasis. Immunochemical analysis showed that sulindac significantly decreased Ki-67-labeled cell proliferation and markedly reduced the expression of phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Raf and mitogen-activated protein kinase kinase 1 and 2. In in vitro experiments with PDAC cells from Pan(kras/p53) mice, sulindac exhibited dose-dependent inhibition of AKR1B10 activity. By silencing AKR1B10 expression through small interfering RNA or by sulindac treatment, these in vitro models showed a reduction in Kras and human DNA-J homolog 2 protein prenylation, and downregulation of phosphorylated C-raf, ERK1/2 and MEK1/2 expression. Our results demonstrate that sulindac inhibits pancreatic carcinogenesis by the inhibition of Kras protein prenylation by targeting AKR1B10.

  13. Storytelling in Projects

    DEFF Research Database (Denmark)

    Munk-Madsen, Andreas; Andersen, Peter Bøgh

    2006-01-01

    project managers should not only be concerned with project plans, but also with project stories. In this paper we explore some basic principles for transforming project plans into appealing stories. We discuss what may happen to stories once they are released into public space. And we illustrate how......Plans and stories are two different ways of communicating about projects. Project plans are formalized descriptions, primarily supporting coordination. Project stories are accounts whose primary function is emotional appeal. Project stories influence the projects’ chances of success. Therefore...... the possibilities of telling favorable stories may have repercussions on the project planning....

  14. The Ethiopian Flora Project

    DEFF Research Database (Denmark)

    Demissew, Sebsebe; Brochmann, Christian; Kelbessa, Ensermu

    2011-01-01

    The account reviews and analyses the scietific projects derived from activities in connection with the Ethiopian Flora Project, including the [Ethiopian] Monocot Project, the Afro-alpine "Sky-island" project, the Vegetation and Ecological Conditions of Plantations Project, the Fire Ecology Projec...

  15. Capital projects coordination

    Directory of Open Access Journals (Sweden)

    Zubović Jovan

    2004-01-01

    Full Text Available This paper looks at the difficulties of managing modem capital projects and endeavors to reduce the complexities to simpler and more understandable terms. It examines the project environment, defines project management and discusses points of difference from traditional management. In the second part of the paper are presented fundamentals for project success for different types of projects.

  16. From project management to project leadership

    NARCIS (Netherlands)

    Braun, F.; Avital, M.

    2010-01-01

    It is virtually a truism that good leadership practices can help project managers with attaining the desired project outcome. However, a better understanding of which leadership practices enable project managers to be more effective warrants further investigation. Subsequently, in this study, we

  17. An IS Project Management Course Project

    Science.gov (United States)

    Frank, Ronald L.

    2010-01-01

    Information Systems curricula should provide project management (PM) theory, current practice, and hands-on experience. The schedule usually does not allow time in Analysis and Design courses for development oriented project management instruction other than a short introduction. Similarly, networking courses usually don't put project management…

  18. Managing Projects for Change: Contextualised Project Management

    Science.gov (United States)

    Tynan, Belinda; Adlington, Rachael; Stewart, Cherry; Vale, Deborah; Sims, Rod; Shanahan, Peter

    2010-01-01

    This paper will detail three projects which focussed on enhancing online learning at a large Australian distance education University within a School of Business, School of Health and School of Education. Each project had special funding and took quite distinctive project management approaches, which reflect the desire to embed innovation and…

  19. 78 FR 16765 - Community Reinvestment Act; Interagency Questions and Answers Regarding Community Reinvestment...

    Science.gov (United States)

    2013-03-18

    ... its assessment area(s)''? If so, how can the Agencies better describe the concept that a financial... reduced-price meals are based on the Federal income poverty guidelines and are stated by household size... criteria for Medicaid recipients, the income criteria generally are based on the state poverty level. Thus...

  20. 78 FR 69671 - Community Reinvestment Act; Interagency Questions and Answers Regarding Community Reinvestment...

    Science.gov (United States)

    2013-11-20

    ... commenters expressed concern that investments in nationwide funds could divert an institution's attention... investments, commenters were divided. Most commenters opposed the creation of a separate category because... organization is an explicit example of a technical assistance activity that could be provided to community...

  1. 75 FR 11641 - Community Reinvestment Act; Interagency Questions and Answers Regarding Community Reinvestment...

    Science.gov (United States)

    2010-03-11

    ... Financial Institutions (CDFIs), New Markets Tax Credit-eligible Community Development Entities, Community... Financial Institutions Examination Council (FFIEC) in 1996 (61 FR 54647), and were last revised on January 6... represented financial institutions and their trade associations, community development advocates and...

  2. I-15 North Project

    Science.gov (United States)

    2013-11-05

    Goals of this project were as follows: (1) Conduct a comprehensive evaluation study on Nevada's I-15 North Design Build Project; (2) Analyze project implementation with respect to construction zone rules by which the contractor had to abide; (3) Anal...

  3. Web Project Management

    OpenAIRE

    Suralkar, Sunita; Joshi, Nilambari; Meshram, B B

    2013-01-01

    This paper describes about the need for Web project management, fundamentals of project management for web projects: what it is, why projects go wrong, and what's different about web projects. We also discuss Cost Estimation Techniques based on Size Metrics. Though Web project development is similar to traditional software development applications, the special characteristics of Web Application development requires adaption of many software engineering approaches or even development of comple...

  4. USAID Anticorruption Projects Database

    Data.gov (United States)

    US Agency for International Development — The Anticorruption Projects Database (Database) includes information about USAID projects with anticorruption interventions implemented worldwide between 2007 and...

  5. Project 2010 Bible

    CERN Document Server

    Marmel, Elaine

    2010-01-01

    A comprehensive reference on the latest version of the leading enterprise project management software: Microsoft Project 2010. Microsoft Project allows users to manage business activities effectively by sharing project information, performing modeling and scenario analyses, standardizizing reporting processes, and more. This soup-to-nuts reference covers both the professional and standard versions of the latest iteration of Microsoft Project, as well as Project Server, so that you can efficiently manage your business projects. Veteran author Elaine Marmel begins with an overview of project man

  6. Project 2010 For Dummies

    CERN Document Server

    Muir, Nancy C

    2010-01-01

    A friendly reference guide to Microsoft Project, the leading enterprise project management software. As project management software, Microsoft Project allows you to oversee your business activities effectively. You can manage resources, share project info, perform modeling and scenario analysis, and standardize reporting processes. This easy-to-understand guide is completely updated to cover the latest changes and newest enhancements to Project 2010 and shows you how to get Project 2010 to work for you. After an introduction to basic project management concepts, you'll discover the mechanics o

  7. Project development symposium

    Energy Technology Data Exchange (ETDEWEB)

    1983-01-01

    Papers were presented on the following: project evaluation; case studies - minerals; finance; applied finance; legal; manpower/industrial relations; and new technologies. Those papers on the coal industry were: mine planning for coal project development; the planning and management of a lignite exploration contract in Thailand; development of the West Cliff extended project; Ulan: a resource development; Saxonvale mine development a case study in project planning and project management; the role of marketing in the development of a new coal project; technical support for coal marketing; infrastructure development for the Ulan project; underground mine project developments; the bucketwheel excavator at Goonyella - a case study; tax aspects of mining development projects; cost of capital mining development projects; and trends in development project finance. 16 papers were abstracted separately.

  8. PROJECT SCOPE MANAGEMENT PROCESS

    Directory of Open Access Journals (Sweden)

    Yana Derenskaya

    2018-01-01

    Full Text Available The purpose of the article is to define the essence of project scope management process, its components, as well as to develop an algorithm of project scope management in terms of pharmaceutical production. Methodology. To carry out the study, available information sources on standards of project management in whole and elements of project scope management in particular are analysed. Methods of system and structural analysis, logical generalization are used to study the totality of subprocesses of project scope management, input and output documents, and to provide each of them. Methods of network planning are used to construct a precedence diagram of project scope management process. Results of the research showed that components of the project scope management are managing the scope of the project product and managing the content of project work. It is the second component is investigated in the presented work as a subject of research. Accordingly, it is defined that project scope management process is to substantiate and bring to the realization the necessary amount of work that ensures the successful implementation of the project (achievement of its goal and objectives of individual project participants. It is also determined that the process of managing the project scope takes into account the planning, definition of the project scope, creation of the structure of project work, confirmation of the scope and management of the project scope. Participants of these subprocesses are: customer, investor, and other project participants – external organizations (contractors of the project; project review committee; project manager and project team. It is revealed that the key element of planning the project scope is the formation of the structure of design work, the justification of the number of works, and the sequence of their implementation. It is recommended to use the following sequence of stages for creating the structure of project work

  9. Introduction to the Project

    DEFF Research Database (Denmark)

    Kuhn, Johan M.; Malchow-Møller, Nikolaj; Sørensen, Anders

    In this note a short introduction to the project “Employment Effects of Entrepreneurs” is presented. First, we describe the purpose of the project; second, we present the background; third, we briefly describe the three papers that constitute the output of the project, and fourth, we discuss two...... important qualifications for the understanding of the contributions and results established in the project....

  10. The virtual GULLIVER project

    NARCIS (Netherlands)

    Trappl, R.; Nijholt, Antinus; Stuk, M.; Zwiers, Jakob

    2002-01-01

    In this paper we discuss our virtual reality project Gulliver. This project is part of a more comprehensive project conceived by two artists, Matjaž Štuk and Alena Hudcovicová, called “Gulliver’s Museum of Living Art��?. Our part of the project involves a virtual reality version of Swift’s Gulliver

  11. Innovations in project activities

    Directory of Open Access Journals (Sweden)

    Serbskaya O.V.

    2016-11-01

    Full Text Available this article considers the ways of project management, models of project management: classical model and the model of flexible designing Agile, pays more attention to the process of project management using Agile model and to the problems of using the project management models in modern conditions.

  12. The 100 People Project

    Science.gov (United States)

    McLeod, Keri

    2007-01-01

    This article describes the 100 People Project and how the author integrates the project in her class. The 100 People Project is a nonprofit organization based in New York City. The organization poses the question: If there were only 100 people in the world, what would the world look like? Through the project, students were taught about ethics in…

  13. Earth System Science Project

    Science.gov (United States)

    Rutherford, Sandra; Coffman, Margaret

    2004-01-01

    For several decades, science teachers have used bottles for classroom projects designed to teach students about biology. Bottle projects do not have to just focus on biology, however. These projects can also be used to engage students in Earth science topics. This article describes the Earth System Science Project, which was adapted and developed…

  14. Projects as value constellations

    DEFF Research Database (Denmark)

    Laursen, Markus

    Creating value has been outlined as very central to projects applying the organizational perspective to projects. It has been suggested that value is created in value constellations or project networks, where actors work together to create value. However, research on the value creation process...... in value constellations is scarce, and through an exploratory study of two project networks in a cultural setting we investigate how value is created in value constellations. We outline how each project may be a distinct type of value constellation, one project creates value for the partners of the network...... as a consortium, and the project creates value primarily for others as a facilitator....

  15. Project stakeholder management

    CERN Document Server

    Eskerod, Pernille

    2013-01-01

    Carrying out a project as planned is not a guarantee for success. Projects may fail because project management does not take the requirements, wishes and concerns of stakeholders sufficiently into account. Projects can only be successful though contributions from stakeholders. And in the end, it is the stakeholders that evaluate whether they find that the project is a success. To manage stakeholders effectively, you need to know your stakeholders, their behaviours and attitudes towards the project. In Project Stakeholder Management, the authors give guidance on how to adopt an analytical and s

  16. Modern project-management

    CERN Multimedia

    CERN. Geneva

    2003-01-01

    This lecture will focus on the following issues: - The current state of the art in Project Management, especially the integration of Project Management with general management activities, and the integrated view of resources allocation. - Overview of the project life cycle, the phases and the deliverables - Necessity and limits of planning in a research environment - Organizational aspects of the projects the roles of the stakeholders - How to get the resources when they are needed - Risk Management in Projects - Earned value - How to keep a project on track (schedule and budget) - Management of the suppliers - Closing of the project

  17. Introduction to the Project

    DEFF Research Database (Denmark)

    Kuhn, Johan M.; Malchow-Møller, Nikolaj; Sørensen, Anders

    In this note a short introduction to the project “Employment Effects of Entrepreneurs” is presented. First, we describe the purpose of the project; second, we present the background; third, we briefly describe the three papers that constitute the output of the project, and fourth, we discuss two ...... important qualifications for the understanding of the contributions and results established in the project.......In this note a short introduction to the project “Employment Effects of Entrepreneurs” is presented. First, we describe the purpose of the project; second, we present the background; third, we briefly describe the three papers that constitute the output of the project, and fourth, we discuss two...

  18. Choice of large projects

    Energy Technology Data Exchange (ETDEWEB)

    Harris, R

    1978-08-01

    Conventional cost/benefit or project analysis has generally not taken into account circumstances in which the project under consideration is large enough that its introduction to the economy would have significant general equilibrium effects. In this paper, rules are examined that would indicate whether such large projects should be accepted or rejected. The rules utilize information yielded by before-project and after-project equilibrium prices and production data. Rules are developed for the undistorted ''first-best'' case, the case in which the fixed costs of the project are covered by distortionary taxation, and for the case of projects producing public goods. 34 references.

  19. Project Half Double

    DEFF Research Database (Denmark)

    Svejvig, Per; Gerstrøm, Anna; Frederiksen, Signe Hedeboe

    The Half Double mission: Project Half Double has a clear mission. We want to succeed in finding a project methodology that can increase the success rate of our projects while increasing the development speed of new products and services. We are convinced that by doing so we can strengthen...... the competitiveness of Denmark and play an important role in the battle for jobs and future welfare. The overall goal is to deliver “Projects in half the time with double the impact” where projects in half the time should be understood as half the time to impact (benefit realization, effect is achieved......) and not as half the time for project execution. The Half Double project journey: It all began in May 2013 when we asked ourselves: How do we create a new and radical project paradigm that can create successful projects? Today we are a movement of hundreds of passionate project people, and it grows larger...

  20. Image understanding architecture: a status report

    Science.gov (United States)

    Weems, Charles C.

    1995-01-01

    The image understanding architecture (IUA) effort is now entering a new phase. The second generation IUA prototypes are nearing completion and our experience with the hardware, extensive software simulations, and additional research are guiding the development of a new generation of the IUA. Furthermore, the primary contractors have been selected for a technology reinvestment project (TRP) award to develop a commercial, off-the-shelf implementation of the new IUA for dual-use embedded applications. Thus, the IUA effort is in the process of making the transition from a research and development project to being a commercially available vision accelerator. IUA development is currently taking place at three sites (Hughes Research Laboratories in Malibu, Calif., Amerinex Artificial Intelligence Inc., and the University of Massachusetts at Amherst). This TRP consortium plans to form a new company to take over all aspects of IUA development and production. This article summarizes the previous efforts, describes the current status of the effort, expands briefly upon some of the basic research that is supporting the next generation IUA, and concludes with a section describing the efforts that will be undertaken in developing the next generation.

  1. Project Finance: Basic Components

    OpenAIRE

    Alfieri Li Ojeda, Jaime

    2015-01-01

    The natural speed of the contemporary world demands large investment projects which require specialized financial techniques such as Project Finance, defined as a fund to finance investment projects of great magnitude. Every Project Finance involves a wide range of elements such as promoters, government, contractors andsuppliers, among others, that will ensure project success. La rapidez del mundo contemporáneo exige que los grandes proyectos de inversión requieran de técnicas financieras ...

  2. Project delivery system (PDS)

    CERN Document Server

    2001-01-01

    As business environments become increasingly competitive, companies seek more comprehensive solutions to the delivery of their projects. "Project Delivery System: Fourth Edition" describes the process-driven project delivery systems which incorporates the best practices from Total Quality and is aligned with the Project Management Institute and ISO Quality Standards is the means by which projects are consistently and efficiently planned, executed and completed to the satisfaction of clients and customers.

  3. IT Project Management Metrics

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available Many software and IT projects fail in completing theirs objectives because different causes of which the management of the projects has a high weight. In order to have successfully projects, lessons learned have to be used, historical data to be collected and metrics and indicators have to be computed and used to compare them with past projects and avoid failure to happen. This paper presents some metrics that can be used for the IT project management.

  4. Methodologies of Project Management

    Directory of Open Access Journals (Sweden)

    Wojciech Macek

    2011-07-01

    Full Text Available This paper presents comparison of three most popular project management standardsbelonging to a wider group of models (for example, PMBOK, Prince 2, CMMI, ISO 10006,BS 6079, IPMA Competence Baseline, European Commission Project Cycle ManagementGuidelines. The author discusses methods of project management according to PMBoK,Prince 2 and ISO 10006, some chosen criteria and fields of knowledge, such as generalregulations of standards, project range management, resources management, and processesconnected with risk, systems of project quality management.

  5. Project Half Double

    DEFF Research Database (Denmark)

    Svejvig, Per; Ehlers, Michael; Adland, Karoline Thorp

    activities carried out within the framework of the projects. The formal part of Project Half Double was initiated in June 2015. We started out by developing, refining and testing the Half Double methodology on seven pilot projects in the first phase of the project, which will end June 2016. The current......Project Half Double has a clear mission to succeed in finding a project methodology that can increase the success rate of our projects while increasing the speed at which we generate new ideas and develop new products and services. Chaos and complexity should be seen as a basic condition...... and as an opportunity rather than a threat and a risk. We are convinced that by doing so, we can strengthen Denmark’s competitiveness and play an important role in the battle for jobs and future welfare. The overall goal is to deliver “projects in half the time with double the impact”, where projects in half the time...

  6. Project management case studies

    CERN Document Server

    Kerzner, Harold R

    2013-01-01

    A new edition of the most popular book of project management case studies, expanded to include more than 100 cases plus a ""super case"" on the Iridium Project Case studies are an important part of project management education and training. This Fourth Edition of Harold Kerzner''s Project Management Case Studies features a number of new cases covering value measurement in project management. Also included is the well-received ""super case,"" which covers all aspects of project management and may be used as a capstone for a course. This new edition:Contains 100-plus case studies drawn from re

  7. The USE Project

    DEFF Research Database (Denmark)

    Frøkjær, E.; Hornbæk, K.; Høegh, Rune Thaarup

    2006-01-01

    This paper provides experience from activities in the USE project. The USE project is a research project that aims at bridging the gap between usability evaluation and user interface design. It is conducted from 2005 to 2008 in collaboration between researchers from Aalborg University and Copenha......This paper provides experience from activities in the USE project. The USE project is a research project that aims at bridging the gap between usability evaluation and user interface design. It is conducted from 2005 to 2008 in collaboration between researchers from Aalborg University...... and Copenhagen University, and developers and managers working in software development organizations....

  8. IT Project Selection

    DEFF Research Database (Denmark)

    Pedersen, Keld

    2016-01-01

    for initiation. Most of the research on project selection is normative, suggesting new methods, but available empirical studies indicate that many methods are seldom used in practice. This paper addresses the issue by providing increased understanding of IT project selection practice, thereby facilitating...... the development of methods that better fit current practice. The study is based on naturalistic decision-making theory and interviews with experienced project portfolio managers who, when selecting projects, primarily rely on political skills, experience and personal networks rather than on formal IT project......-selection methods, and these findings point to new areas for developing new methodological support for IT project selection....

  9. One project's waste is another project's resource

    International Nuclear Information System (INIS)

    Short, J.

    1997-01-01

    The author describes the efforts being made toward pollution prevention within the DOE complex, as a way to reduce overall project costs, in addition to decreasing the amount of waste to be handled. Pollution prevention is a concept which is trying to be ingrained into project planning. Part of the program involves the concept that ultimately the responsibility for waste comes back to the generator. Parts of the program involve efforts to reuse materials and equipment on new projects, to recycle wastes to generate offsetting revenue, and to increase awareness, accountability and incentives so as to stimulate action on this plan. Summaries of examples are presented in tables

  10. Integrated project support environments the ASPECT project

    CERN Document Server

    Brown, Alan W

    1991-01-01

    A major part of software engineering developments involve the use of computing tools which facilitate the management, maintenance, security, and building of long-scale software engineer projects. Consequently, there have been a proliferation of CASE tools and IPSES. This book looks at IPSES in general and the ASPECT project in particular, providing design and implementation details, as well as locating ASPECT in IPSE developments.Survey of integrated project support environments for more efficient software engineering**Description of a large scale IPSE--ASPECT**Evaluation of formal methods in

  11. MANAGING MULTICULTURAL PROJECT TEAMS

    Directory of Open Access Journals (Sweden)

    Cezar SCARLAT

    2014-06-01

    Full Text Available The article is based on literature review and authors’ own recent experience in managing multicultural project teams, in international environment. This comparative study considers two groups of projects: technical assistance (TA projects versus information technology (IT projects. The aim is to explore the size and structure of the project teams – according to the team formation and its lifecycle, and to identify some distinctive attributes of the project teams – both similarities and differences between the above mentioned types of projects. Distinct focus of the research is on the multiculturalism of the project teams: how the cultural background of the team members influences the team performance and team management. Besides the results of the study are the managerial implications: how the team managers could soften the cultural clash, and avoid inter-cultural misunderstandings and even conflicts – in order to get a better performance. Some practical examples are provided as well.

  12. Construction project management handbook.

    Science.gov (United States)

    2012-03-01

    The purpose of the FTA Construction Project Management Handbook is to provide guidelines for use by public transit agencies (Agen-cies) undertaking substantial construction projects, either for the first time or with little prior experience with cons...

  13. BioProject

    Data.gov (United States)

    U.S. Department of Health & Human Services — The BioProject database provides an organizational framework to access information about research projects with links to data that have been or will be deposited...

  14. The Phebus FP project

    International Nuclear Information System (INIS)

    Delchambre, P.; Von der Hardt, P.

    1989-01-01

    This report summarizes the pre-project studies concerning the PHEBUS FP facility. After recalling the programme objectives, it describes the projected modifications to the PHEBUS reactor, outlines new installations and justifies the selected options

  15. Number projection method

    International Nuclear Information System (INIS)

    Kaneko, K.

    1987-01-01

    A relationship between the number projection and the shell model methods is investigated in the case of a single-j shell. We can find a one-to-one correspondence between the number projected and the shell model states

  16. Successful project management

    CERN Document Server

    Young, Trevor L

    2016-01-01

    Successful Project Management, 5th edition, is an essential guide for anyone who wants to improve the success rate of their projects. It will help managers to maintain a balance between the demands of the customer, the project, the team and the organization. Covering the more technical aspects of a project from start to completion it contains practised and tested techniques, covering project conception and start-up, how to manage stake holders, effective risk management, project planning and launch and execution. Also including a brand new glossary of key terms, it provides help with evaluating your project as well as practical checklists and templates to ensure success for any ambitious project manager. With over one million copies sold, the hugely popular Creating Success series covers a wide variety of topic, with the latest editions including new chapters such as Tough Conversations and Treating People Right. This indispensable business skills collection is suited to a variety of roles, from someone look...

  17. Unicycle Project Report

    OpenAIRE

    Thomson, S

    2010-01-01

    The Unicycle project implemented an institutional Open Educational Resource repository with a view to ensuring sustainability in approach by embedding OER as an Assessment, Learning and Teaching strategy. This is the final submitted report for the project.

  18. Collaborative Contracting in Projects

    NARCIS (Netherlands)

    Suprapto, M.

    2016-01-01

    Project practitioners have increasingly recognized the importance of collaborative relationships to ensure successful executions of projects. However, the ability to sustain and consistenly drive real collaborative attitudes and behavior for achieving the desired outcomes remains of enduring

  19. Project Tasks in Robotics

    DEFF Research Database (Denmark)

    Sørensen, Torben; Hansen, Poul Erik

    1998-01-01

    Description of the compulsary project tasks to be carried out as a part of DTU course 72238 Robotics......Description of the compulsary project tasks to be carried out as a part of DTU course 72238 Robotics...

  20. Venezuela's Bolivarian Schools Project.

    Science.gov (United States)

    Diaz, Maria Magnolia Santamaria

    2002-01-01

    Discusses efforts by the Venezuelan government to improve the nation's school infrastructure through the Bolivarian Schools Project administered by the Ministry of Education, Culture and Sport. The project set educational principles which are guiding current school building efforts. (EV)

  1. Project management process.

    Science.gov (United States)

    2007-03-01

    This course provides INDOT staff with foundational knowledge and skills in project management principles and methodologies. INDOTs project management processes provide the tools for interdisciplinary teams to efficiently and effectively deliver pr...

  2. The Alzheimer's Project

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues The Alzheimer's Project Past Issues / Spring 2009 Table of Contents ... of this page please turn Javascript on. The Alzheimer's Project A 4-Part Documentary Series Starting May ...

  3. Capital Projects Application (CPA)

    Data.gov (United States)

    General Services Administration — Capital Projects application (CPA) provides users with the ability to maintain project related financial data for Budget Activity (BA) 51, 55, 64, 01, 02, 03, 04....

  4. Earned value project management

    CERN Document Server

    Fleming, Quentin W

    2010-01-01

    Organizations that follow the principles of good Earned Value Management (EVM) create an environment that allows teams to successfully operate and thrive ? even in the face of challenges that could negatively impact their projects. Earned Value Project Management (EVPM) is a methodology used to measure and communicate the real physical progress of a project taking into account the work completed, the time taken and the costs incurred to complete that work. As a result, EVPM allows more educated and effective management decision-making, which helps evaluate and control project risk by measuring project progress in monetary terms. In the first two editions of Earned Value Project Management, Quentin W. Fleming and Joel M. Koppelman provided guidance for project management practitioners already familiar with EVPM, was well as those who were new to the use of this technique. The third edition expanded the information available on of EVPM for medium and smaller projects while still being relevant for larger projec...

  5. IX Disposition Project - project management plan

    International Nuclear Information System (INIS)

    Choi, I.G.

    1994-01-01

    This report presents plans for resolving saving and disposal concerns for ion exchange modules, cartridge filters and columns. This plan also documents the project baselines for schedules, cost, and technical information

  6. Project Management Performance Drivers

    OpenAIRE

    Ra’ad, Mohammed A.; Najdawi, Mohammad K.

    2010-01-01

    The practice of project management has gained enormous importance over the past several years in various business industries. “In industries as diverse as pharmaceuticals, software, and aerospace, projects drive business” (Wheatley). This gain of importance can be attributed to the magnitude of the impact project performance results in terms of time, cost, and scope have over the project performing entity. “On the basis of data released by the Bureau of Economic Analysis, part of the US De...

  7. Managing clinical improvement projects.

    Science.gov (United States)

    Phillips, Joanna; Simmonds, Lorraine

    This paper, the second of a three-part series looking at change management tools, provides a practical guide on how to use common project management principles in practice. Much of the literature on project management focuses on the business arena, with little reference to clinical settings. Identifying this literature and understanding its relevance to managing projects in healthcare can be difficult. This article provides a practical guide to identifying the key principles of good project management and applying these in health settings.

  8. The Dwarf Project: Vidojevica

    Science.gov (United States)

    Vince, O.

    2013-05-01

    The DWARF project is an important international project for observing eclipsing binary stars and searching for third companion which orbit around both stars. Recently, a group of researchers at the Astronomical Observatory of Belgrade joined this project using the 60 cm telescope at the Astronomical Station Vidojevica for observations. All the equipment and the human potential involved with this project from Serbia will be described in this paper.

  9. Project Management Techniques

    OpenAIRE

    Mihalache Anita; Salagean Liana

    2010-01-01

    Project management is a technique that can aid in the planning, scheduling, and monitoring of complex projects characterized by numerous, non repetitive jobs called activities. Examples of projects that would use project management include: - developing a mass rapid – transit system for a metropolitan area; - organizing the relocation of a corporate headquarters; - planning the production of a concert, film, or play; - developing and marketing a new automobile; - constructing a high – rise of...

  10. Project evaluation: main characteristics

    OpenAIRE

    Moutinho, Nuno

    2010-01-01

    — The evaluation process of real investment projects must consider not only the traditional financial approach, but also non-financial aspects. Non financial analysis can provide additional relevant information about projects. We investigate financial and non-financial areas most relevant in project appraisal. We present main critical success factors and areas of analysis that lead to the perception of project success. Finally, companies are segmented to verify its financial and non-financial...

  11. Project mechanisms challenges

    International Nuclear Information System (INIS)

    Perthuis, Ch. de

    2005-06-01

    The project mechanism complete the quotas systems concerning the carbon dioxide emissions market. The author explains and discusses these mechanisms and provides a panorama of the existing and developing projects. More specially she brings information on the mechanism of clean developments and renewable energies, the coordinated mechanisms, the agricultural projects, the financing of the projects and the exchange systeme of the New south Wales. (A.L.B.)

  12. ORGANIZATIONAL PROJECT MANAGEMENT MATURITY

    Directory of Open Access Journals (Sweden)

    Yana Derenskaya

    2017-11-01

    Full Text Available The present article is aimed at developing a set of recommendations for achieving a higher level of organizational project maturity at a given enterprise. Methodology. For the purposes of the current research, the available information sources on the components of project management system are analysed; the essence of “organizational maturity” and the existing models of organizational maturity are studied. The method of systemic and structural analysis, as well as the method of logical generalization, are employed in order to study the existing models of organizational maturity, to describe levels of organizational maturity, and finally to develop a set of methodological recommendations for achieving a higher level of organizational project maturity at a given enterprise. The results of the research showed that the core elements of project management system are methodological, organizational, programtechnical, and motivational components. Project management encompasses a wide range of issues connected with organizational structure, project team, communication management, project participants, etc. However, the fundamental basis for developing project management concept within a given enterprise starts with defining its level of organizational maturity. The present paper describes various models of organizational maturity (staged, continuous, petal-shaped and their common types (H. Кеrzner Organizational Maturity Model, Berkeley PM Maturity Model, Organizational Project Management Maturity Model, Portfolio, Program & Project Management Maturity Model. The analysis of available theoretic works showed that the notion “organizational project maturity” refers to the capability of an enterprise to select projects and manage them with the intention of achieving its strategic goals in the most effective way. Importantly, the level of maturity can be improved by means of formalizing the acquired knowledge, regulating project-related activities

  13. Pilot Project: analysis, development and projection

    OpenAIRE

    Tapia Abril, Verónica Emilia; Chérrez Rodas, Karina; García Pesántez, Gabriela Rosana; Maldonado Marchán, María Elisa; Bustamante Montesdeoca, José Luis

    2014-01-01

    Since the introduction of ICT in architecture and teaching, pedagogies of education have faced their learning paradigms change. Institutes of higher education have folded to this motion and have undergone a process of change by implementing multimedia elements in their subjects. Through the pilot project educational videos that aim to meet the highest standards of educational videos described by Van Dam have been developed. The project expects to generate educational videos for different depa...

  14. Building Project Competence

    DEFF Research Database (Denmark)

    Pemsel, Sofia; Wiewiora, Anna

    This research investigates the development of project competence, and particularly, three related dynamic capabilities (shifting, adapting, leveraging) that contribute to project competence development. In doing so, we make use of the emerging literature on knowledge governance and theorize how...... of dynamic capability building promoting project competence development....

  15. The Llama Project.

    Science.gov (United States)

    Ganzel, Candy; Stuglik, Jan

    2003-01-01

    At a suburban Indiana elementary school, the Project Approach serves as the basis of the curriculum in all Kindergarten classrooms. The four classes of 5- and 6-year-old children at this school chose to study llamas. This article discusses how the project evolved, describes the three phases of the project, and provides teachers' reflections on the…

  16. Nuclear safety projects 1995

    International Nuclear Information System (INIS)

    Carl-Erik Christoffersen

    1996-01-01

    Action plans for the prevention of contamination in the Arctic regions is concretized in a number of international projects. The Norwegian Radiation Protection Authority is responsible for the follow-up of 13 projects. The report describes the development of these projects in 1995

  17. Projection: A Bibliography.

    Science.gov (United States)

    Pedrini, D. T.; Pedrini, Bonnie C.

    Sigmund Freud and his associates did much clinical work with the dynamic of projection, especially with regard to paranoid symptoms and syndromes. Much experimental work has also been done with projection. Sears evaluated the results of some of those studies. Murstein and Pryer sub-classified projection and reviewed typical studies. The…

  18. Mayan Forest Road Projects

    DEFF Research Database (Denmark)

    Conde, Dalia Amor

    2008-01-01

    Road-building projects in the Mayan Biosphere Reserve to connect Mexico and Guatemala were subjected to a cost-benefit evaluation. Up to an estimated 311,000 hectares of jaguar habitat were found to be at risk of deforestation due to these projects. Some of the projects were shown to have negativ...... of continued conservation rather than road development....

  19. Projection Models 2010

    DEFF Research Database (Denmark)

    Illerup, J. B.; Birr-Pedersen, K.; Mikkelsen, M. H

    Models for projection of SO2-, NOx-, NMVOC- and NH3-emissions to the atmosphere have been developed and the Danish emissions have been projected until 2010 from a basis scenario including all implemented and planned measures. The projections of the four pollutants indicate that it may be difficult...

  20. Project Communications Management

    OpenAIRE

    José C. Santiago-Guevara; Mauricio Rojas-Contreras; Luis A. Esteban-Villamizar

    2013-01-01

    This article presents a review in relation to the object of study: Communications Management as an important factor in the management of projects. The review includes the most relevant and most renowned authors in the field of project management, focusing on telecommunications projects, which lets you define a communications management model.

  1. Designing Project Management

    NARCIS (Netherlands)

    Heintz, John Linke; Lousberg, L.; Wamelink, J.W.F.; Saari, A.; Huovinen, P.

    2016-01-01

    In this paper we introduce the concept of Designing Project Management. On the basis of our earlier work, we suggest that there is still a gap between what is known from recent project management literature and what project managers can structurally help in the effectiveness of their work. Assuming

  2. Humane Education Projects Handbook.

    Science.gov (United States)

    Junior League of Ogden, UT.

    This handbook was developed to promote interest in humane education and to encourage the adoption of humane education projects. Although specifically designed to assist Junior Leagues in developing such projects, the content should prove valuable to animal welfare organizations, zoos, aquariums, nature centers, and other project-oriented groups…

  3. MRS project management

    International Nuclear Information System (INIS)

    Doman, J.W.; Vlahakis, J.

    1992-01-01

    Management of projects under the control of the Office of Civilian Radioactive Waste Management within the Department of Energy is subject to overview by a variety of internal and external entities. This paper reports that effective project management often requires balancing of conflicting directions and conflicting agendas of the different entities in order to proceed with implementation of the Monitored Retrievable Storage project

  4. Risks management in project planning

    OpenAIRE

    Stankevičiūtė, Roberta

    2017-01-01

    Project management consists of two very important aspects – managing the right project and managing the project right. To know that you are managing the right project you need to ensure that your project is based on an actual requirement and that your project goal is relevant and beneficial. And professional project planning assists in managing project the right way. The project planning process is very time consuming and is one of the most important parts of the project management process. T...

  5. Project report - an overview of the project and experiences with project management

    DEFF Research Database (Denmark)

    Jørgensen, Michael Søgaard; Mikkelsen, Bent Egberg

    1996-01-01

    A collection of the project planning and the experiences with project management from the Catering 2000 project.As appendieces articles etc. from journals, newspapers etc. about the project.......A collection of the project planning and the experiences with project management from the Catering 2000 project.As appendieces articles etc. from journals, newspapers etc. about the project....

  6. Final Technical Report - Modernization of the Boulder Canyon Hydroelectric Project

    Energy Technology Data Exchange (ETDEWEB)

    Taddeucci, Joe [Dept. of Public Works, Boulder, CO (United States). Utilities Division

    2013-03-29

    The Boulder Canyon Hydroelectric Project (BCH) was purchased by the City of Boulder, CO (the city) in 2001. Project facilities were originally constructed in 1910 and upgraded in the 1930s and 1940s. By 2009, the two 10 MW turbine/generators had reached or were nearing the end of their useful lives. One generator had grounded out and was beyond repair, reducing plant capacity to 10 MW. The remaining 10 MW unit was expected to fail at any time. When the BCH power plant was originally constructed, a sizeable water supply was available for the sole purpose of hydroelectric power generation. Between 1950 and 2001, that water supply had gradually been converted to municipal water supply by the city. By 2001, the water available for hydroelectric power generation at BCH could not support even one 10 MW unit. Boulder lacked the financial resources to modernize the facilities, and Boulder anticipated that when the single, operational historical unit failed, the project would cease operation. In 2009, the City of Boulder applied for and received a U.S. Department of Energy (DOE) grant for $1.18 million toward a total estimated project cost of $5.155 million to modernize BCH. The federal funding allowed Boulder to move forward with plant modifications that would ensure BCH would continue operation. Federal funding was made available through the American Recovery and Reinvestment Act (ARRA) of 2009. Boulder determined that a single 5 MW turbine/generator would be the most appropriate capacity, given the reduced water supply to the plant. Average annual BCH generation with the old 10 MW unit had been about 8,500 MW-hr, whereas annual generation with a new, efficient turbine could average 11,000 to 12,000 MW-hr. The incremental change in annual generation represents a 30% increase in generation over pre-project conditions. The old turbine/generator was a single nozzle Pelton turbine with a 5-to-1 flow turndown and a maximum turbine/generator efficiency of 82%. The new unit is a

  7. Underestimation of Project Costs

    Science.gov (United States)

    Jones, Harry W.

    2015-01-01

    Large projects almost always exceed their budgets. Estimating cost is difficult and estimated costs are usually too low. Three different reasons are suggested: bad luck, overoptimism, and deliberate underestimation. Project management can usually point to project difficulty and complexity, technical uncertainty, stakeholder conflicts, scope changes, unforeseen events, and other not really unpredictable bad luck. Project planning is usually over-optimistic, so the likelihood and impact of bad luck is systematically underestimated. Project plans reflect optimism and hope for success in a supposedly unique new effort rather than rational expectations based on historical data. Past project problems are claimed to be irrelevant because "This time it's different." Some bad luck is inevitable and reasonable optimism is understandable, but deliberate deception must be condemned. In a competitive environment, project planners and advocates often deliberately underestimate costs to help gain project approval and funding. Project benefits, cost savings, and probability of success are exaggerated and key risks ignored. Project advocates have incentives to distort information and conceal difficulties from project approvers. One naively suggested cure is more openness, honesty, and group adherence to shared overall goals. A more realistic alternative is threatening overrun projects with cancellation. Neither approach seems to solve the problem. A better method to avoid the delusions of over-optimism and the deceptions of biased advocacy is to base the project cost estimate on the actual costs of a large group of similar projects. Over optimism and deception can continue beyond the planning phase and into project execution. Hard milestones based on verified tests and demonstrations can provide a reality check.

  8. Fundamentals of Project Management

    CERN Document Server

    Heagney, Joseph

    2011-01-01

    With sales of more than 160,000 copies, Fundamentals of Project Management has helped generations of project managers navigate the ins and outs of every aspect of this complex discipline. Using a simple step-by-step approach, the book is the perfect introduction to project management tools, techniques, and concepts. Readers will learn how to: ò Develop a mission statement, vision, goals, and objectives ò Plan the project ò Create the work breakdown structure ò Produce a workable schedule ò Understand earned value analysis ò Manage a project team ò Control and evaluate progress at every stage.

  9. Visualizations as Projection Devices

    DEFF Research Database (Denmark)

    Harty, Chris; Holm Jacobsen, Peter; Tryggestad, Kjell

    The aim of this paper is to inquire into the role of project visualizations in shaping healthcare spaces and practices. The study draws upon an ethnographic field study from a large on-going hospital construction project in Denmark, and focuses on the early phases of on-boarding the design team...... into the project organization. During the on-boarding visualizations multiplies in form, content and purpose, ranging from paper and digitally based projections of clinical work spaces and practices for the future hospital building in use, to paper and digitally based projections of the cost budget and time...

  10. Managing Projects with KPRO

    Science.gov (United States)

    Braden, Barry M.

    2004-01-01

    How does a Project Management Office provide: Consistent, familiar, easily used scheduling tools to Project Managers and project team members? Provide a complete list of organization resources available for use on the project? Facilitate resource tracking and visibility? Provide the myriad reports that the organization requires? Facilitate consistent budget planning and cost performance information? Provide all of this to the entire organization? Provide for the unique requirement of the organization? and get people to use it? Answer: Implementation of the Kennedy space Center Projects and Resources Online (KPRO), a modified COTS solution.

  11. Project Decision Chain

    DEFF Research Database (Denmark)

    Rolstadås, Asbjørn; Pinto, Jeffrey K.; Falster, Peter

    2015-01-01

    To add value to project performance and help obtain project success, a new framework for decision making in projects is defined. It introduces the project decision chain inspired by the supply chain thinking in the manufacturing sector and uses three types of decisions: authorization, selection......, and plan decision. A primitive decision element is defined where all the three decision types can be accommodated. Each task in the primitive element can in itself contain subtasks that in turn will comprise new primitive elements. The primitive elements are nested together in a project decision chain....

  12. Scheduling for decommissioning projects

    International Nuclear Information System (INIS)

    Podmajersky, O.E.

    1987-01-01

    This paper describes the Project Scheduling system being employed by the Decommissioning Operations Contractor at the Shippingport Station Decommissioning Project (SSDP). Results from the planning system show that the project continues to achieve its cost and schedule goals. An integrated cost and schedule control system (C/SCS) which uses the concept of earned value for measurement of performance was instituted in accordance with DOE orders. The schedule and cost variances generated by the C/SCS system are used to confirm management's assessment of project status. This paper describes the types of schedules and tools used on the SSDP project to plan and monitor the work, and identifies factors that are unique to a decommissioning project that make scheduling critical to the achievement of the project's goals. 1 fig

  13. Managing Distributed Software Projects

    DEFF Research Database (Denmark)

    Persson, John Stouby

    Increasingly, software projects are becoming geographically distributed, with limited face-toface interaction between participants. These projects face particular challenges that need careful managerial attention. This PhD study reports on how we can understand and support the management...... of distributed software projects, based on a literature study and a case study. The main emphasis of the literature study was on how to support the management of distributed software projects, but also contributed to an understanding of these projects. The main emphasis of the case study was on how to understand...... the management of distributed software projects, but also contributed to supporting the management of these projects. The literature study integrates what we know about risks and risk-resolution techniques, into a framework for managing risks in distributed contexts. This framework was developed iteratively...

  14. ASEAN projects reviewed.

    Science.gov (United States)

    1980-01-01

    The ASEAN Population Expert Group met in Manila and was followed by a meeting of the ASEAN heads of population programs, during the period November 5-10, 1979. Heads of population programs from Indonesia, Malaysia, Singapore, Thailand, and the Philippines attended. The meetings were held to review progress-to-date on phase 1 projects and to consider the development of an expanded population program. 5 projects funded by UNFPA are reviewed in tabular form with the project, the sponsoring country, date of implementation, data analysis, and date of completion. Suggestions were made for improving and extending these projects and it was also suggested that all projects being developed and proposed should include a section on use of research. 7 new projects were proposed as phase 2 projects. The 1st, sponsored by Malaysia, deals with women in development; project 2, lead by Thailand, will investigate population movement and its effect on development; project 3, led by the Philippines, will develop and strengthen national population information systems and networks in ASEAN countries; project 4, led by Indonesia, is directed towards institutional development and exchanges of personnel; project 5, led by the Philippines, will examine population and development dynamics and the man/resources balance; project 6, led by Thailand, will develop ASEAN social indicators; and project 7, led by Indonesia and Malaysia, will make a comprehensive analysis of existing medical/health care and family planning systems. It was recommended that an executive director of the proposed ASEAN population coordination unit should be appointed to expedite the recommendations of the meeting related to preparation and submission of phase 2 project proposals.

  15. Lessons Learned from the 200 West Pump and Treatment Facility Construction Project at the US DOE Hanford Site - A Leadership for Energy and Environmental Design (LEED) Gold-Certified Facility - 13113

    Energy Technology Data Exchange (ETDEWEB)

    Dorr, Kent A.; Freeman-Pollard, Jhivaun R.; Ostrom, Michael J. [CH2M HILL Plateau Remediation Company, P.O. Box 1600, MSIN R4-41, 99352 (United States)

    2013-07-01

    CH2M Hill Plateau Remediation Company (CHPRC) designed, constructed, commissioned, and began operation of the largest groundwater pump and treatment facility in the U.S. Department of Energy's (DOE) nationwide complex. This one-of-a-kind groundwater pump and treatment facility, located at the Hanford Nuclear Reservation Site (Hanford Site) in Washington State, was built to an accelerated schedule with American Recovery and Reinvestment Act (ARRA) funds. There were many contractual, technical, configuration management, quality, safety, and Leadership in Energy and Environmental Design (LEED) challenges associated with the design, procurement, construction, and commissioning of this $95 million, 52,000 ft groundwater pump and treatment facility to meet DOE's mission objective of treating contaminated groundwater at the Hanford Site with a new facility by June 28, 2012. The project team's successful integration of the project's core values and green energy technology throughout design, procurement, construction, and start-up of this complex, first-of-its-kind Bio Process facility resulted in successful achievement of DOE's mission objective, as well as attainment of LEED GOLD certification (Figure 1), which makes this Bio Process facility the first non-administrative building in the DOE Office of Environmental Management complex to earn such an award. (authors)

  16. Lessons Learned from the 200 West Pump and Treatment Facility Construction Project at the US DOE Hanford Site - A Leadership for Energy and Environmental Design (LEED) Gold-Certified Facility - 13113

    International Nuclear Information System (INIS)

    Dorr, Kent A.; Freeman-Pollard, Jhivaun R.; Ostrom, Michael J.

    2013-01-01

    CH2M Hill Plateau Remediation Company (CHPRC) designed, constructed, commissioned, and began operation of the largest groundwater pump and treatment facility in the U.S. Department of Energy's (DOE) nationwide complex. This one-of-a-kind groundwater pump and treatment facility, located at the Hanford Nuclear Reservation Site (Hanford Site) in Washington State, was built to an accelerated schedule with American Recovery and Reinvestment Act (ARRA) funds. There were many contractual, technical, configuration management, quality, safety, and Leadership in Energy and Environmental Design (LEED) challenges associated with the design, procurement, construction, and commissioning of this $95 million, 52,000 ft groundwater pump and treatment facility to meet DOE's mission objective of treating contaminated groundwater at the Hanford Site with a new facility by June 28, 2012. The project team's successful integration of the project's core values and green energy technology throughout design, procurement, construction, and start-up of this complex, first-of-its-kind Bio Process facility resulted in successful achievement of DOE's mission objective, as well as attainment of LEED GOLD certification (Figure 1), which makes this Bio Process facility the first non-administrative building in the DOE Office of Environmental Management complex to earn such an award. (authors)

  17. Perspectives on projects, project success and team work

    OpenAIRE

    Thompson, Karen

    2015-01-01

    This paper brings together perspectives on projects, project success and team work as a background to two graphical tools for considering project success and individual capabilities for working in a project team.

  18. Quality Assurance Project Plan for Citizen Science Projects

    Science.gov (United States)

    The Quality Assurance Project Plan is necessary for every project that collects or uses environmental data. It documents the project planning process and serves as a blueprint for how your project will run.

  19. Project Management and the Project Manager: A Strategy for ...

    African Journals Online (AJOL)

    International Journal of Development and Management Review ... collapse, project failure, project abandonment, project cost and time overruns, etc. ... component parts that constitute project management in the building construction industry.

  20. Theory of Abelian projection

    International Nuclear Information System (INIS)

    Ogilvie, M.C.

    1999-01-01

    Analytic methods for Abelian projection are developed. A number of results are obtained related to string tension measurements. It is proven that even without gauge fixing, Abelian projection yields string tensions of the underlying non-Abelian theory. Strong arguments are given for similar results in the case where gauge fixing is employed. The methods used emphasize that the projected theory is derived from the underlying non-Abelian theory rather than vice versa. In general, the choice of subgroup used for projection is not very important, and need not be Abelian. While gauge fixing is shown to be in principle unnecessary for the success of Abelian projection, it is computationally advantageous for the same reasons that improved operators, e.g., the use of fat links, are advantageous in Wilson loop measurements. Two other issues, Casimir scaling and the conflict between projection and critical universality, are also discussed. copyright 1999 The American Physical Society

  1. Battleground Energy Recovery Project

    Energy Technology Data Exchange (ETDEWEB)

    Bullock, Daniel [USDOE Gulf Coast Clean Energy Application Center, Woodlands, TX (United States)

    2011-12-31

    In October 2009, the project partners began a 36-month effort to develop an innovative, commercial-scale demonstration project incorporating state-of-the-art waste heat recovery technology at Clean Harbors, Inc., a large hazardous waste incinerator site located in Deer Park, Texas. With financial support provided by the U.S. Department of Energy, the Battleground Energy Recovery Project was launched to advance waste heat recovery solutions into the hazardous waste incineration market, an area that has seen little adoption of heat recovery in the United States. The goal of the project was to accelerate the use of energy-efficient, waste heat recovery technology as an alternative means to produce steam for industrial processes. The project had three main engineering and business objectives: Prove Feasibility of Waste Heat Recovery Technology at a Hazardous Waste Incinerator Complex; Provide Low-cost Steam to a Major Polypropylene Plant Using Waste Heat; and Create a Showcase Waste Heat Recovery Demonstration Project.

  2. J-PARC project

    International Nuclear Information System (INIS)

    Nagamiya, Shoji

    2004-01-01

    From Japanese fiscal year JFY01, which started on April 1, 2001, a new accelerator project to provide high-intensity proton beams proceeded into its construction phase. This project, which is now called the Japan Proton Accelerator Research Complex (J-PARC) project, is conducted under a cooperation of two institutions, KEK and Japan Atomic Energy Research Institution. We set a goal to achieve 1 MW proton beams at 3 GeV and 0.75 MW beams at 50 GeV. The project will be completed within six years, with the anticipated first beams in the spring of 2007. In this article I will describe (a) the project itself, (b) sciences to be pursued at this new accelerator complex and (c) the present status and future plans of the project

  3. Photovoltaic demonstration projects

    Energy Technology Data Exchange (ETDEWEB)

    Kaut, W [Commission of the European Communities, Brussels (Belgium); Gillett, W B; Hacker, R J [Halcrow Gilbert Associates Ltd., Swindon (GB)

    1992-12-31

    This publication, comprising the proceedings of the fifth contractor`s meeting organized by the Commission of the European Communities, Directorate-General for Energy, provides an overview of the photovoltaic demonstration projects which have been supported in the framework of the energy demonstration programme since 1983. It includes reports by each of the contractors who submitted proposals in 1987 and 1988, describing progress within their projects. Projects accepted from earlier calls for proposals and not yet completed were reviewed by a rapporteur and are discussed in the summary section. The results of the performance monitoring of all projects and the lessons drawn from the practical experience of the projects are also presented in the summaries and conclusions. Contractors whose projects were submitted in 1989 were also present at the meeting and contributed to the reported discussions. This proceeding is divided into four sessions (General, Housing, technical presentations, other applications) and 24 papers are offered.

  4. Evolution of the U.S. energy service company industry: Market size and project performance from 1990–2008

    International Nuclear Information System (INIS)

    Larsen, Peter H.; Goldman, Charles A.; Satchwell, Andrew

    2012-01-01

    The U.S. energy service company (ESCO) industry is an example of a private sector business model where energy savings are delivered to customers primarily through the use of performance-based contracts. This study was conceived as a snapshot of the ESCO industry prior to the economic slowdown and the introduction of federal stimulus funding mandated by enactment of the American Recovery and Reinvestment Act of 2009 (ARRA). This study utilizes two parallel analytic approaches to characterize ESCO industry and market trends in the U.S.: (1) a “top-down” approach involving a survey of individual ESCOs to estimate aggregate industry activity and (2) a “bottom-up” analysis of a database of ∼3250 projects (representing over $8B in project investment) that reports market trends including installed EE retrofit strategies, project installation costs and savings, project payback times, and benefit-cost ratios over time. Despite the onset of a severe economic recession, the U.S. ESCO industry managed to grow at about 7% per year between 2006 and 2008. ESCO industry revenues were about $4.1 billion in 2008 and ESCOs anticipate accelerated growth through 2011 (25% per year). We found that 2484 ESCO projects in our database generated ∼$4.0 billion ($2009) in net, direct economic benefits to their customers. We estimate that the ESCO project database includes about 20% of all U.S. ESCO market activity from 1990–2008. Assuming the net benefits per project are comparable for ESCO projects that are not included in the LBNL database, this would suggest that the ESCO industry has generated ∼$23 billion in net direct economic benefits for customers at projects installed between 1990 and 2008. There is empirical evidence confirming that the industry is evolving by installing more comprehensive and complex measures—including onsite generation and measures to address deferred maintenance—but this evolution has significant implications for customer project economics

  5. AAEC nuclear power projections

    International Nuclear Information System (INIS)

    Khoe, G.; Fredsall, J.; Scurr, I.; Plotnikoff, W.

    1981-01-01

    The nuclear power capacity projections developed in the May-June period of 1981 by the AAEC are presented. There have been downward revisions for nearly all countries with centrally planned economies. Projections for the year 2000 for the Western World have decreased in aggregate by 4.7% (27Gw) compared to those of 1980. However, this reduction is less than the previous estimate reduction and there appears to have been a stabilisation in the projection

  6. What is project finance?

    OpenAIRE

    João M. Pinto

    2017-01-01

    Project finance is the process of financing a specific economic unit that the sponsors create, in which creditors share much of the venture’s business risk and funding is obtained strictly for the project itself. Project finance creates value by reducing the costs of funding, maintaining the sponsors financial flexibility, increasing the leverage ratios, avoiding contamination risk, reducing corporate taxes, improving risk management, and reducing the costs associated with market ...

  7. Computer Assets Recovery Project

    Science.gov (United States)

    CortesPena, Aida Yoguely

    2010-01-01

    This document reports on the project that was performed during the internship of the author. The project involved locating and recovering machines in various locations that Boeing has no need for, and therefore requires that they be transferred to another user or transferred to a non-profit organization. Other projects that the author performed was an inventory of toner and printers, loading new computers and connecting them to the network.

  8. Operational Waste Volume Projection

    Energy Technology Data Exchange (ETDEWEB)

    STRODE, J.N.

    2000-08-28

    Waste receipts to the double-shell tank system are analyzed and wastes through the year 2015 are projected based on generation trends of the past 12 months. A computer simulation of site operations is performed, which results in projections of tank fill schedules, tank transfers, evaporator operations, tank retrieval, and aging waste tank usage. This projection incorporates current budget planning and the clean-up schedule of the Tri-Party Agreement. Assumptions were current as of June. 2000.

  9. Organization of project management

    International Nuclear Information System (INIS)

    Schmidt, R.

    1975-01-01

    When speaking about interfaces within a project and their management, one has to understand and define what an interface is. In general, each component facing another one and each person working on a project with another person represents an interface. Therefore a project will consist practically in its entirety of interfaces with components and people sandwiched between them. This paper is limited to the most important interfaces with a focus on the problems occuring at them and their resolution. (orig.) [de

  10. Operational waste volume projection

    International Nuclear Information System (INIS)

    Koreski, G.M.; Strode, J.N.

    1995-06-01

    Waste receipts to the double-shell tank system are analyzed and wastes through the year 2015 are projected based on generation trends of the past 12 months. A computer simulation of site operations is performed, which results in projections of tank fill schedules, tank transfers, evaporator operations, tank retrieval, and aging waste tank usage. This projection incorporates current budget planning and the clean-up schedule of the tri-party agreement. Assumptions are current as of June 1995

  11. PPP projects in transport

    DEFF Research Database (Denmark)

    Petersen, Ole Helby; Carpintero, Samuel

    2014-01-01

    Public–private partnerships (PPPs) have been extensively used in Spain for the procurement of light rail systems. This paper analyses five projects that have been in operation for more than five years. The authors examine the reasoning behind the selection of the PPP projects, risk......-sharing mechanisms, competition among private providers, and overall cost-effectiveness. The paper demonstrates a need for more rigorous assessments of the merits of PPP projects before they are initiated....

  12. Operational Waste Volume Projection

    International Nuclear Information System (INIS)

    STRODE, J.N.

    2000-01-01

    Waste receipts to the double-shell tank system are analyzed and wastes through the year 2015 are projected based on generation trends of the past 12 months. A computer simulation of site operations is performed, which results in projections of tank fill schedules, tank transfers, evaporator operations, tank retrieval, and aging waste tank usage. This projection incorporates current budget planning and the clean-up schedule of the Tri-Party Agreement. Assumptions were current as of June. 2000

  13. Existence of Projective Planes

    OpenAIRE

    Perrott, Xander

    2016-01-01

    This report gives an overview of the history of finite projective planes and their properties before going on to outline the proof that no projective plane of order 10 exists. The report also investigates the search carried out by MacWilliams, Sloane and Thompson in 1970 [12] and confirms their result by providing independent verification that there is no vector of weight 15 in the code generated by the projective plane of order 10.

  14. Microwave solidification project overview

    Energy Technology Data Exchange (ETDEWEB)

    Sprenger, G.

    1993-01-01

    The Rocky Flats Plant Microwave Solidification Project has application potential to the Mixed Waste Treatment Project and the The Mixed Waste Integrated Program. The technical areas being addressed include (1) waste destruction and stabilization; (2) final waste form; and (3) front-end waste handling and feed preparation. This document covers need for such a program; technology description; significance; regulatory requirements; and accomplishments to date. A list of significant reports published under this project is included.

  15. Oskarshamn 1-project FENIX

    International Nuclear Information System (INIS)

    Sjoeqvist, N.G.

    1994-01-01

    This paper summarizes the actions to be taken in a large re-start and backfitting project such as the Fenix project. It describes the organization, planning and financial management, safety criteria and licensing procedures, safety concept report, health and safety. The results from the unique full system decontamination of the reactor pressure vessel is described. The project is still ongoing and therefore other results and lessons learnt are not reported. (author) 9 figs

  16. Microwave solidification project overview

    International Nuclear Information System (INIS)

    Sprenger, G.

    1993-01-01

    The Rocky Flats Plant Microwave Solidification Project has application potential to the Mixed Waste Treatment Project and the The Mixed Waste Integrated Program. The technical areas being addressed include (1) waste destruction and stabilization; (2) final waste form; and (3) front-end waste handling and feed preparation. This document covers need for such a program; technology description; significance; regulatory requirements; and accomplishments to date. A list of significant reports published under this project is included

  17. Embedded Linux projects using Yocto project cookbook

    CERN Document Server

    González, Alex

    2015-01-01

    If you are an embedded developer learning about embedded Linux with some experience with the Yocto project, this book is the ideal way to become proficient and broaden your knowledge with examples that are immediately applicable to your embedded developments. Experienced embedded Yocto developers will find new insight into working methodologies and ARM specific development competence.

  18. Project Risk Management

    Science.gov (United States)

    Jr., R. F. Miles

    1995-01-01

    Project risk management is primarily concerned with performance, reliability, cost, and schedule. Environmental risk management is primarily concerned with human health and ecological hazards and likelihoods. This paper discusses project risk management and compares it to environmental risk management, both with respect to goals and implementation. The approach of the Jet Propulsion Laboratory to risk management is presented as an example of a project risk management approach that is an extension to NASA NHB 7120.5: Management of Major System Programs and Projects.

  19. HERMES project management I

    CERN Multimedia

    CERN. Geneva

    2013-01-01

    A two-hours course on the HERMES Project Management Methodology to the attention of Project Leaders and Project Participants. The methodology is quickly presented; the focus is put on the roles and responsibilities and on the project initiation phase. The course is given in French with slides in English. On April 22nd 2013, a new version of the HERMES methodology was made public. For practical reasons, this course is still given based on the 2009 version of HERMES (a.k.a. HERMES 4).

  20. Scrum Project Management

    CERN Document Server

    Pries, Kim H

    2010-01-01

    Scrum, which was originally invented solely for software development, can now be applied to all types of projects. This book shows project managers how to implement Scrum by explaining the artifacts, rituals, and roles used. The text provides Scrum planning methods to control project scope and schedule as well as Scrum tracking methods to focus teams on improving throughput and streamlining communications. The authors show how to combine traditional project methods with Scrum and how to adapt the familiar work breakdown structure to create Scrum backlogs and sprints. They also demonstrate how