WorldWideScience

Sample records for program atp proposal

  1. Paradox applications integration ATP's for MAC and mass balance programs

    International Nuclear Information System (INIS)

    Russell, V.K.; Mullaney, J.E.

    1994-01-01

    The K Basins Materials Accounting (MAC) and Material Balance (MBA) database system were set up to run under one common applications program. This Acceptance Test Plan (ATP) describes how the code was to be tested to verify its correctness. The scope of the tests is minimal, since both MAC and MBA have already been tested in detail as stand-alone programs

  2. ATP signals

    DEFF Research Database (Denmark)

    Novak, Ivana

    2016-01-01

    The Department of Biology at the University of Copenhagen explains the function of ATP signalling in the pancreas......The Department of Biology at the University of Copenhagen explains the function of ATP signalling in the pancreas...

  3. Physics issues of a proposed program, SPIRIT

    International Nuclear Information System (INIS)

    Ji, Hantao; Yamada, Masaaki

    2000-01-01

    Physics issues of the proposed program, SPIRIT (Self-organized Plasma with Induction, Reconnection, and Induction Techniques) are discussed. The main purpose of this program is to explore the physics of global stability and sustainment of compact toroids, including FRC (field reversed configuration) as well as low-aspect-ratio RFP (reversed field pinch), spheromak and spherical torus. (author)

  4. Proposed tokamak poloidal field system development program

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, J.D.; Vogel, H.F.; Warren, R.W.; Weldon, D.M.

    1977-05-01

    A program is proposed to develop poloidal field components for TNS and EPR size tokamak devices and to test these components in realistic circuits. Emphasis is placed upon the development of the most difficult component, the superconducting ohmic-heating coil. Switches must also be developed for testing the coils, and this switching technology is to be extended to meet the requirements for the large scale tokamaks. Test facilities are discussed; power supplies, including a homopolar to drive the coils, are considered; and poloidal field systems studies are proposed.

  5. Natural Programming: Project Overview and Proposal

    National Research Council Canada - National Science Library

    Myers, Brad

    1998-01-01

    .... The Natural Programming Project is developing general principles, methods, and programming language designs that will significantly reduce the amount of learning and effort needed to write programs...

  6. A proposal of neutron science research program

    International Nuclear Information System (INIS)

    Suzuki, Y.; Yasuda, H.; Tone, T.; Mizumoto, M.

    1996-01-01

    A conception of Neutron Science Research Program (NSRP) has been proposed in Japan Atomic Energy Research Institute (JAERI) since 1994 as a future big project. The NSRP aims at exploring new basic science and nuclear energy science by a high-intensity proton accelerator. It is a complex composed of a proton linac and seven research facilities with each different target system. The proton linac is required to supply the high-intensity proton beam with energy up to 1.5 GeV and current 10 mA on average. The scientific research facilities proposed, are as follows: Thermal/Cold Neutron Facility for the neutron scattering experiments, Neutron Irradiation Facility for materials science, Neutron Physics Facility for nuclear data measurement, OMEGA/Nuclear Energy Facility for nuclear waste transmutation and fuel breeding, Spallation RI Beam Facility for nuclear physics, Meson/Muon Facility for meson and muon physics and their applications and Medium Energy Beam Facility for accelerator technology development, medical use, etc. Research and development have been carried out for the components of the injector system of the proton linac; an ion source, an RFQ linac and a part of DTL linac. The conceptual design work and research and development activities for NSRP have been started in the fiscal year, 1996. Construction term will be divided into two phases; the completion of the first phase is expected in 2003, when the proton linac will produce 1.5 GeV, 1 mA beam by reflecting the successful technology developments. (author)

  7. Natural Programming: Project Overview and Proposal

    National Research Council Canada - National Science Library

    Myers, Brad

    1998-01-01

    End-users must write programs to control many different kinds of applications. Examples include multimedia authoring, controlling robots, defining manufacturing processes, setting up simulations, programming agents, scripting, etc...

  8. Research waste management program - An action proposal

    International Nuclear Information System (INIS)

    Costa Ramos, A.; Esposito, I.

    1997-01-01

    The Brazilian Nuclear Energy Commission planned prepared and established a Research Waste Management Program, started in 1996, in order to map, to analyze and to solve the common problems in the research field. The specific study done included a large number of academic institutions. The procedures, results and operational methodology used by the Team linked to the Program, in one of the research institutions studied where corrective actions were implemented to avoid unnecessary dose to the public, will be discussed in this article. (author)

  9. Federal Aviation Administration retained savings program proposal

    International Nuclear Information System (INIS)

    Hostick, D.J.; Larson, L.L.; Hostick, C.J.

    1998-03-01

    Federal legislation allows federal agencies to retain up to 50% of the savings associated with implementing energy efficiency and water conservation measures and practices. Given budget pressures to reduce expenditures, the use of retained savings to fund additional projects represents a source of funds outside of the traditional budget cycle. The Southwest Region Federal Aviation Administration (FAA) has tasked Pacific Northwest National Laboratory (PNNL) to develop a model retained savings program for Southwest Region FAA use and as a prototype for consideration by the FAA. PNNL recommends the following steps be taken in developing a Southwest Region FAA retained savings program: Establish a retained savings mechanism. Determine the level at which the retained savings should be consolidated into a fund. The preliminary recommendation is to establish a revolving efficiency loan fund at the regional level. Such a mechanism allows some consolidation of savings to fund larger projects, while maintaining a sense of facility ownership in that the funds will remain within the region

  10. Object oriented distributed programming: studies and proposals

    International Nuclear Information System (INIS)

    Guerraoui, Rachid

    1992-01-01

    This thesis contributes to the investigation of the object concept in distributed programming. Henceforth, this programming style has become a reality in the computer science world, since it allows to increase of the availability of applications and to decrease their execution time. Nevertheless, designing a distributed application is a hard task: the various abstraction levels that must be considered hinder the software reusability and maintenance, while errors and concurrent accesses are often sources of executions incoherence. The object concept improves the software modularity, and raises the computing abstraction level. Integrating distribution related aspects into the object model brings up the issues of expressing the concurrency and maintaining the coherency. The investigation of these problems in this thesis has been guided by a major concern for the preservation of the intrinsic properties of object-orientation, and the orthogonality of the solutions given. The main contributions of the thesis are: (i) the classification, regarding modularity, of the different design alternatives for object-oriented concurrent languages; (ii) the evaluation of various transactional mechanisms in object-based concurrent languages, and the design of an atomic asynchronous communication protocol named ACS; (iii) the definition of a transaction-based object-oriented concurrent language called KAROS; (iv) the implementation of a modular framework which allows to combine in a same application, various concurrency control and error recovery mechanisms; (v) the identification of a formal property, named general atomicity, which constitutes a correctness criteria for atomic objects specifications. (author) [fr

  11. TEACHING ADMINISTRATION: PROPOSAL OF THE PROGRAM CONTENT

    Directory of Open Access Journals (Sweden)

    Eduardo Ribeiro Rodrigues

    2016-08-01

    Full Text Available The National Curriculum Guidelines established by MEC (Brazilian Ministry of Education, define the specific areas of vocational training content that should be included in the curricular organization of undergraduate courses in Brazil, without suggesting or detailing which content should be offered in each area. In this sense, this study aims at proposing the course syllabus for the financial area for the undergraduate courses of Management. To achieve this goal, the curriculum matrices and the teaching plans of the financial discipline of the undergraduate courses on Management with the highest grades in ENADE were analyzed. Based on this survey, seven disciplines were elaborated with the professional qualification contents of the area, with 560 hours/class in total, distributed in the curriculum matrix, according to their goals: presentation of corporate finance and personal finance, short and long-term financial decisions, financial economic analysis, financial planning, and financial strategies.

  12. 100-N pilot project: Proposed consolidated groundwater monitoring program

    International Nuclear Information System (INIS)

    Borghese, J.V.; Hartman, M.J.; Lutrell, S.P.; Perkins, C.J.; Zoric, J.P.; Tindall, S.C.

    1996-11-01

    This report presents a proposed consolidated groundwater monitoring program for the 100-N Pilot Project. This program is the result of a cooperative effort between the Hanford Site contractors who monitor the groundwater beneath the 100-N Area. The consolidation of the groundwater monitoring programs is being proposed to minimize the cost, time, and effort necessary for groundwater monitoring in the 100-N Area, and to coordinate regulatory compliance activities. The integrity of the subprograms requirements remained intact during the consolidation effort. The purpose of this report is to present the proposed consolidated groundwater monitoring program and to summarize the process by which it was determined

  13. 78 FR 40084 - Proposed Requirement-Migrant Education Program Consortium Incentive Grant Program

    Science.gov (United States)

    2013-07-03

    ... DEPARTMENT OF EDUCATION 34 CFR Chapter II Proposed Requirement--Migrant Education Program... educational agencies (SEAs) under the Migrant Education Program (MEP) Consortium Incentive Grant (CIG) Program... the interstate or intrastate coordination of migrant education programs by addressing key needs of...

  14. Proposal of programming standards for a computerized protection system

    International Nuclear Information System (INIS)

    Ehrenberger, W.; Voges, U.

    1975-05-01

    In process computer systems with high safety and reliability requirements, correctness of the software has to be proved. During the development of a program specific guidelines should be met in order to facilitate the verification of its correctness. This paper is a collection of relevant proposals. (orig.) [de

  15. Proposal for Supply Chain Concentration in the Traditional MBA Program

    Science.gov (United States)

    Ramaswamy, K. V.

    2012-01-01

    The purpose of this proposal is to develop and implement a concentration in Supply Chain Management in the existing traditional MBA program effective fall 2012. Houston is the hub for many multinational oil and energy companies, large healthcare systems, wholesale/retail businesses, engineering and construction companies, and is a major city along…

  16. ATP Release Channels

    Directory of Open Access Journals (Sweden)

    Akiyuki Taruno

    2018-03-01

    Full Text Available Adenosine triphosphate (ATP has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels. Such channels must possess two minimum qualifications for ATP permeation: anion permeability and a large ion-conducting pore. Currently, five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1, volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR anion channels, and maxi-anion channels (MACs. Recently, major breakthroughs have been made in the field by molecular identification of CALHM1 as the action potential-dependent ATP-release channel in taste bud cells, LRRC8s as components of VRACs, and SLCO2A1 as a core subunit of MACs. Here, the function and physiological roles of these five groups of ATP-release channels are summarized, along with a discussion on the future implications of understanding these channels.

  17. GRI proposes to hold the line on research program

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This paper reports that the Gas Research Institute has proposed a 1993 US research and development program totaling $201.8 million, the same level as the 1991 but down from $212.9 million this year. GRI filed the 1993 proposal and its 1993-97 R and D plan with the Federal Energy Regulatory Commission. If FERC approves the plan, interstate gas pipeline companies would support the GRI research by collecting a surcharge of 1.51 cents/Mcf on nondiscounted gas transactions and 8 cents/Mcf/month on uniform demand or reservations. The proposed budget is based on a revised funding mechanism FERC is considering for GRI. The research agency's general expanses and capital budget would remain at the 1992 level of $9.8 million

  18. Journey in guidelines for lipid management: From adult treatment panel (ATP-I to ATP-III and what to expect in ATP-IV

    Directory of Open Access Journals (Sweden)

    P G Talwalkar

    2013-01-01

    Full Text Available Adult Treatment Panel (ATP, an expert panel to supervise cholesterol management was set up under the aegis of National Cholesterol Education Program (NCEP in 1985. Since then NCEP-ATP has been revising and framing guidelines to enable clinician to deliver better treatment to cardiovascular patients and to educate general people. As a result, considerable reduction in cardiovascular related deaths has been observed in recent times. All three ATP guidelines viz. ATP-I, ATP-II and ATP-III have targeted low density lipoprotein as their primary goal. The ATP-III guideline was updated in the light of evidences from 5-major clinical trials and was released in 2004. It added therapeutic lifestyle changes, concept of risk equivalents, Framingham CHD-risk score non-high density lipoprotein cholesterol (non-HDL-C as secondary target and gave strong emphasis on metabolic risk factors. The earlier treat-to-target paradigm faced fierce criticism from clinicians across the globe because of insufficient proof of safety and benefits of treating patients with respect to an individual′s low density lipoprotein (LDL level. Further, demonstration of non-HDL-C and total cholesterol/HDL-C ratio as strong predictors of overall cardiovascular risk foresees new guidelines. A tailored-treatment approach was suggested instead of LDL-C target based treatment approach which was soundly based on direct clinical trials evidences and proposes treatment based on individual′s overall 5- to 10-year cardiovascular risk irrespective of LDL-C level, leading to lower number of people on high dose/s of statins. Recent report of the Cholesterol Treatment Trialist′s Collaborators meta-analysis strongly supported primary prevention of LDL with statins in low risk individuals and showed that its benefits completely outweighed its known hazards. Markers other than LDL-C like apolipoprotein B, non-HDL-C and total cholesterol/HDL-C ratio would take precedence in the risk assessment and

  19. Cost estimate for a proposed GDF Suez LNG testing program

    Energy Technology Data Exchange (ETDEWEB)

    Blanchat, Thomas K.; Brady, Patrick Dennis; Jernigan, Dann A.; Luketa, Anay Josephine; Nissen, Mark R.; Lopez, Carlos; Vermillion, Nancy; Hightower, Marion Michael

    2014-02-01

    At the request of GDF Suez, a Rough Order of Magnitude (ROM) cost estimate was prepared for the design, construction, testing, and data analysis for an experimental series of large-scale (Liquefied Natural Gas) LNG spills on land and water that would result in the largest pool fires and vapor dispersion events ever conducted. Due to the expected cost of this large, multi-year program, the authors utilized Sandia's structured cost estimating methodology. This methodology insures that the efforts identified can be performed for the cost proposed at a plus or minus 30 percent confidence. The scale of the LNG spill, fire, and vapor dispersion tests proposed by GDF could produce hazard distances and testing safety issues that need to be fully explored. Based on our evaluations, Sandia can utilize much of our existing fire testing infrastructure for the large fire tests and some small dispersion tests (with some modifications) in Albuquerque, but we propose to develop a new dispersion testing site at our remote test area in Nevada because of the large hazard distances. While this might impact some testing logistics, the safety aspects warrant this approach. In addition, we have included a proposal to study cryogenic liquid spills on water and subsequent vaporization in the presence of waves. Sandia is working with DOE on applications that provide infrastructure pertinent to wave production. We present an approach to conduct repeatable wave/spill interaction testing that could utilize such infrastructure.

  20. Proposed equation of state experimental program at NOVA/NIF

    International Nuclear Information System (INIS)

    Holmes, N.C.; Cauble, R.; Celliers, P.; Collins, G.; DaSilva, L.; Hammel, B.; Stewart, R.; Strand, O.; Sullivan, A.

    1996-03-01

    The high pressure equations of state of materials must be accurately known for confident design, simulation, and interpretation of ICF target experiments and for weapons. Here, the authors sketch out a program to perform precise and accurate equation of state (EOS) experiments using large, high-power lasers. The program is divided into three phases: (1) a driver qualification program which will determine the necessary drive and target design parameters; (2) characterization of low and high-Z standard materials; (3) accurate impedance-match experiments to determine equations of state of materials of interest relative to the qualified standards. Novel methods are proposed for the first phase which are an order of magnitude more sensitive than those applied previously. They identify and describe the choices for standards and the samples slated for initial studies. In all cases, their goal is to obtain data that is of sufficiently high quality to serve for design purposes and to validate theories of material response at high pressures of the order of 1--10 TPa. This is particularly important right now, for materials such as CH plastics and hydrogen (DT). In addition, they will suggest a program for EOS measurements for P > 10 TPa, the region of maximum theoretical EOS uncertainty for many materials

  1. Real-time object-oriented programming: studies and proposals

    International Nuclear Information System (INIS)

    Fouquier, Gilles

    1996-01-01

    This thesis contributes to the introduction of real-time features in object-oriented programming. Object-oriented programming favours modularity and reusability. Therefore, its application to real-time introduces many theoretical and conceptual problems. To deal with these problems, a new real-time object-oriented programming model is presented. This model is based on the active object model which allows concurrence and maintains the encapsulation property. The real-time aspect is treated by replacing the concept of task by the concept of method processing and by associating a real-time constraint to each message (priority or deadline). The set of all the running methods is scheduled. This model, called ATOME, contains several sub-models to deal with the usual concurrence control integrating their priority and deadline processing. The classical HPF and EDF scheduling avoid priority or deadline inversion. This model and its variants are new proposals to program real-time applications in the object-oriented way, therefore easing reusability and code writing. The feasibility of this approach is demonstrated by extending and existing active object-based language to real-time, in using the rules defined in the ATOME model. (author) [fr

  2. ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Masaki Nakano

    2017-08-01

    Full Text Available Parkinson's disease is assumed to be caused by mitochondrial dysfunction in the affected dopaminergic neurons in the brain. We have recently created small chemicals, KUSs (Kyoto University Substances, which can reduce cellular ATP consumption. By contrast, agonistic ligands of ERRs (estrogen receptor-related receptors are expected to raise cellular ATP levels via enhancing ATP production. Here, we show that esculetin functions as an ERR agonist, and its addition to culture media enhances glycolysis and mitochondrial respiration, leading to elevated cellular ATP levels. Subsequently, we show the neuroprotective efficacies of KUSs, esculetin, and GSK4716 (an ERRγ agonist against cell death in Parkinson's disease models. In the surviving neurons, ATP levels and expression levels of α-synuclein and CHOP (an ER stress-mediated cell death executor were all rectified. We propose that maintenance of ATP levels, by inhibiting ATP consumption or enhancing ATP production, or both, would be a promising therapeutic strategy for Parkinson's disease.

  3. 77 FR 63537 - Greenhouse Gas Reporting Program: Proposed Amendments and Confidentiality Determinations for...

    Science.gov (United States)

    2012-10-16

    ... Greenhouse Gas Reporting Program: Proposed Amendments and Confidentiality Determinations for Subpart I...-AR61 Greenhouse Gas Reporting Program: Proposed Amendments and Confidentiality Determinations for... Manufacturing, of the Greenhouse Gas Reporting Rule. Proposed changes include revising certain calculation...

  4. NCEP ATP III dan Framingham score

    OpenAIRE

    Hasan, Refli; Fahila, Reny

    2016-01-01

    Laporan ini merupakan Program Pendidikan Kolesterol National yang diperbaharui yaitu pedoman klinis untuk melakukan pengujian kolesterol dan manajemen. ATP III dibuat berdasarkan bukti dan laporan ekstensif yang akan menjadi referensi dan rekomendasi ilmiah. Laporan ATP III dapat dijadikan pedoman untuk pemberian terapi penurun kolesterol yang intensif dalam praktek. Pedoman ini hanya sebagai informasi , tidak dapat mempengaruhi secara mutlak dalam penilaian klinis dokter yang akhirnya menent...

  5. R and D Proposal for the National Muon Acccelerator Program

    International Nuclear Information System (INIS)

    2010-01-01

    This document contains a description of a multi-year national R and D program aimed at completing a Design Feasibility Study (DFS) for a Muon Collider and, with international participation, a Reference Design Report (RDR) for a muon-based Neutrino Factory. It also includes the supporting component development and experimental efforts that will inform the design studies and permit an initial down-selection of candidate technologies for the ionization cooling and acceleration systems. We intend to carry out this plan with participants from the host national laboratory (Fermilab), those from collaborating U.S. national laboratories (ANL, BNL, Jlab, LBNL, and SNAL), and those from a number of other U.S. laboratories, universities, and SBIR companies. The R and D program that we propose will provide the HEP community with detailed information on future facilities based on intense beams of muons - the Muon Collider and the Neutrino Factory. We believe that these facilities offer the promise of extraordinary physics capabilities. The Muon Collider presents a powerful option to explore the energy frontier and the Neutrino Factory gives the opportunity to perform the most sensitive neutrino oscillation experiments possible, while also opening expanded avenues for the study of new physics in the neutrino sector. The synergy between the two facilities presents the opportunity for an extremely broad physics program and a unique pathway in accelerator facilities. Our work will give clear answers to the questions of expected capabilities and performance of these muon-based facilities, and will provide defensible ranges for their cost. This information, together with the physics insights gained from the next-generation neutrino and LHC experiments, will allow the HEP community to make well-informed decisions regarding the optimal choice of new facilities. We believe that this work is a critical part of any broad strategic program in accelerator R and D and, as the P5 panel has

  6. R&D Proposal for the National Muon Acccelerator Program

    Energy Technology Data Exchange (ETDEWEB)

    2010-02-01

    This document contains a description of a multi-year national R&D program aimed at completing a Design Feasibility Study (DFS) for a Muon Collider and, with international participation, a Reference Design Report (RDR) for a muon-based Neutrino Factory. It also includes the supporting component development and experimental efforts that will inform the design studies and permit an initial down-selection of candidate technologies for the ionization cooling and acceleration systems. We intend to carry out this plan with participants from the host national laboratory (Fermilab), those from collaborating U.S. national laboratories (ANL, BNL, Jlab, LBNL, and SNAL), and those from a number of other U.S. laboratories, universities, and SBIR companies. The R&D program that we propose will provide the HEP community with detailed information on future facilities based on intense beams of muons - the Muon Collider and the Neutrino Factory. We believe that these facilities offer the promise of extraordinary physics capabilities. The Muon Collider presents a powerful option to explore the energy frontier and the Neutrino Factory gives the opportunity to perform the most sensitive neutrino oscillation experiments possible, while also opening expanded avenues for the study of new physics in the neutrino sector. The synergy between the two facilities presents the opportunity for an extremely broad physics program and a unique pathway in accelerator facilities. Our work will give clear answers to the questions of expected capabilities and performance of these muon-based facilities, and will provide defensible ranges for their cost. This information, together with the physics insights gained from the next-generation neutrino and LHC experiments, will allow the HEP community to make well-informed decisions regarding the optimal choice of new facilities. We believe that this work is a critical part of any broad strategic program in accelerator R&D and, as the P5 panel has recently

  7. R&D PROPOSAL FOR THE NATIONAL MUON ACCELERATOR PROGRAM

    Energy Technology Data Exchange (ETDEWEB)

    Muon Accelerator Program; Zisman, Michael S.; Geer, Stephen

    2010-02-24

    This document contains a description of a multi-year national R&D program aimed at completing a Design Feasibility Study (DFS) for a Muon Collider and, with international participation, a Reference Design Report (RDR) for a muon-based Neutrino Factory. It also includes the supporting component development and experimental efforts that will inform the design studies and permit an initial down-selection of candidate technologies for the ionization cooling and acceleration systems. We intend to carry out this plan with participants from the host national laboratory (Fermilab), those from collaborating U.S. national laboratories (ANL, BNL, Jlab, LBNL, and SNAL), and those from a number of other U.S. laboratories, universities, and SBIR companies. The R&D program that we propose will provide the HEP community with detailed information on future facilities based on intense beams of muons--the Muon Collider and the Neutrino Factory. We believe that these facilities offer the promise of extraordinary physics capabilities. The Muon Collider presents a powerful option to explore the energy frontier and the Neutrino Factory gives the opportunity to perform the most sensitive neutrino oscillation experiments possible, while also opening expanded avenues for the study of new physics in the neutrino sector. The synergy between the two facilities presents the opportunity for an extremely broad physics program and a unique pathway in accelerator facilities. Our work will give clear answers to the questions of expected capabilities and performance of these muon-based facilities, and will provide defensible ranges for their cost. This information, together with the physics insights gained from the next-generation neutrino and LHC experiments, will allow the HEP community to make well-informed decisions regarding the optimal choice of new facilities. We believe that this work is a critical part of any broad strategic program in accelerator R&D and, as the P5 panel has recently

  8. Comments on proposed legislation to restructure DOE's uranium enrichment program

    International Nuclear Information System (INIS)

    1991-04-01

    This book focuses on H.R.145, H.R.788, and S.210. Each of the proposed bills would restructure DOE's enrichment program as a government corporation with private financing and would encourage the eventual sale of the corporation to the private sector. In doing so, the bills would, among other things, allow the corporation to set prices to maximize long-term returns; establish a fund to meet the costs of decontamination, decommissioning, and other environmental cleanup costs associated with uranium enrichment activities; transfer interest in DOE's new atomic vapor laser isotope separation (AVLIS) process to the new corporation; and, except for H.R. 145, require the government to pay its share of the costs to clean up mill tailings (mining wastes) generated under government contracts

  9. The ATP/DNA Ratio Is a Better Indicator of Islet Cell Viability Than the ADP/ATP Ratio

    Science.gov (United States)

    Suszynski, T.M.; Wildey, G.M.; Falde, E.J.; Cline, G.W.; Maynard, K. Stewart; Ko, N.; Sotiris, J.; Naji, A.; Hering, B.J.; Papas, K.K.

    2009-01-01

    Real-time, accurate assessment of islet viability is critical for avoiding transplantation of nontherapeutic preparations. Measurements of the intracellular ADP/ATP ratio have been recently proposed as useful prospective estimates of islet cell viability and potency. However, dead cells may be rapidly depleted of both ATP and ADP, which would render the ratio incapable of accounting for dead cells. Since the DNA of dead cells is expected to remain stable over prolonged periods of time (days), we hypothesized that use of the ATP/DNA ratio would take into account dead cells and may be a better indicator of islet cell viability than the ADP/ATP ratio. We tested this hypothesis using mixtures of healthy and lethally heat-treated (HT) rat insulinoma cells and human islets. Measurements of ATP/DNA and ADP/ATP from the known mixtures of healthy and HT cells and islets were used to evaluate how well these parameters correlated with viability. The results indicated that ATP and ADP were rapidly (within 1 hour) depleted in HT cells. The fraction of HT cells in a mixture correlated linearly with the ATP/DNA ratio, whereas the ADP/ADP ratio was highly scattered, remaining effectively unchanged. Despite similar limitations in both ADP/ADP and ATP/DNA ratios, in that ATP levels may fluctuate significantly and reversibly with metabolic stress, the results indicated that ATP/DNA was a better measure of islet viability than the ADP/ATP ratio. PMID:18374063

  10. Programming in a proposed 9X distributed Ada

    Science.gov (United States)

    Waldrop, Raymond S.; Volz, Richard A.; Goldsack, Stephen J.; Holzbach-Valero, A. A.

    1991-01-01

    The studies of the proposed Ada 9X constructs for distribution, now referred to as AdaPT are reported. The goals for this time period were to revise the chosen example scenario and to begin studying about how the proposed constructs might be implemented. The example scenario chosen is the Submarine Combat Information Center (CIC) developed by IBM for the Navy. The specification provided by IBM was preliminary and had several deficiencies. To address these problems, some changes to the scenario specification were made. Some of the more important changes include: (1) addition of a system database management function; (2) addition of a fourth processing unit to the standard resources; (3) addition of an operator console interface function; and (4) removal of the time synchronization function. To implement the CIC scenario in AdaPT, the decided strategy were publics, partitions, and nodes. The principle purpose for implementing the CIC scenario was to demonstrate how the AdaPT constructs interact with the program structure. While considering ways that the AdaPt constructs might be translated to Ada 83, it was observed that the partition construct could reasonably be modeled as an abstract data type. Although this gives a useful method of modeling partitions, it does not at all address the configuration aspects on the node construct.

  11. Technical Proposal Salton Sea Geothermal Power Pilot Plant Program

    Energy Technology Data Exchange (ETDEWEB)

    None

    1975-03-28

    The proposed Salton Sea Geothermal Power Pilot Plant Program comprises two phases. The objective of Phase 1 is to develop the technology for power generation from high-temperature, high-salinity geothermal brines existing in the Salton Sea known geothermal resources area. Phase 1 work will result in the following: (a) Completion of a preliminary design and cost estimate for a pilot geothermal brine utilization facility. (b) Design and construction of an Area Resource Test Facility (ARTF) in which developmental geothermal utilization concepts can be tested and evaluated. Program efforts will be divided into four sub-programs; Power Generation, Mineral Extraction, Reservoir Production, and the Area Resources Test Facility. The Power Generation Subprogram will include testing of scale and corrosion control methods, and critical power cycle components; power cycle selection based on an optimization of technical, environmental and economic analyses of candidate cycles; preliminary design of a pilot geothermal-electric generating station to be constructed in Phase 2 of this program. The Mineral Extraction Subprogram will involve the following: selection of an optimum mineral recovery process; recommendation of a brine clean-up process for well injection enhancement; engineering, construction and operation of mineral recovery and brine clean-up facilities; analysis of facility operating results from environmental, economical and technical point-of-view; preliminary design of mineral recovery and brine clean-up facilities of sufficient size to match the planned pilot power plant. The Reservoir Production Subprogram will include monitoring the operation and maintenance of brine production, handling and injection systems which were built with private funding in phase 0, and monitoring of the brine characteristics and potential subsidence effects during well production and injection. Based on the above, recommendations and specifications will be prepared for production and

  12. R and D PROPOSAL FOR THE NATIONAL MUON ACCELERATOR PROGRAM

    International Nuclear Information System (INIS)

    Zisman, Michael S.; Geer, Stephen

    2010-01-01

    This document contains a description of a multi-year national R and amp;D program aimed at completing a Design Feasibility Study (DFS) for a Muon Collider and, with international participation, a Reference Design Report (RDR) for a muon-based Neutrino Factory. It also includes the supporting component development and experimental efforts that will inform the design studies and permit an initial down-selection of candidate technologies for the ionization cooling and acceleration systems. We intend to carry out this plan with participants from the host national laboratory (Fermilab), those from collaborating U.S. national laboratories (ANL, BNL, Jlab, LBNL, and SNAL), and those from a number of other U.S. laboratories, universities, and SBIR companies. The R and D program that we propose will provide the HEP community with detailed information on future facilities based on intense beams of muons--the Muon Collider and the Neutrino Factory. We believe that these facilities offer the promise of extraordinary physics capabilities. The Muon Collider presents a powerful option to explore the energy frontier and the Neutrino Factory gives the opportunity to perform the most sensitive neutrino oscillation experiments possible, while also opening expanded avenues for the study of new physics in the neutrino sector. The synergy between the two facilities presents the opportunity for an extremely broad physics program and a unique pathway in accelerator facilities. Our work will give clear answers to the questions of expected capabilities and performance of these muon-based facilities, and will provide defensible ranges for their cost. This information, together with the physics insights gained from the next-generation neutrino and LHC experiments, will allow the HEP community to make well-informed decisions regarding the optimal choice of new facilities. We believe that this work is a critical part of any broad strategic program in accelerator R and D and, as the P5 panel has

  13. The United States foreign research reactor spent nuclear fuel acceptance program: Proposal to modify the program

    International Nuclear Information System (INIS)

    Messick, C.E.

    2005-01-01

    The United States Department of Energy (DOE), in consultation with the Department of State (DOS), adopted the Nuclear Weapons Nonproliferation Policy Concerning Foreign Research Reactor Spent Nuclear Fuel in May 1996. The policy was slated to expire in May 2009. However, in October 2003, a petition requesting a program extension was delivered to the United States Secretary of Energy from a group of research reactor operators from foreign countries. In April 2004, the Secretary directed DOE undertake an analysis, as required by the National Environmental Policy Act (NEPA), to consider potential extension of the Program. On December 1, 2004, a Federal Register Notice was issued approving the program extension. This paper discusses the findings from the NEPA analysis and the potential changes in the program that may result from implementation of the proposed changes. (author)

  14. 75 FR 71513 - Senior Community Service Employment Program; Notice of Proposed Rulemaking, Additional Indicator...

    Science.gov (United States)

    2010-11-23

    ... additional performance indicator for volunteer work. The Proposed Rule adds a new additional indicator to... Program; Notice of Proposed Rulemaking, Additional Indicator on Volunteer Work; Proposed Rule #0;#0... work in the Senior Community Service Employment Program (SCSEP). Specifically, this rule proposes to...

  15. 75 FR 60398 - California: Proposed Authorization of State Hazardous Waste Management Program Revision

    Science.gov (United States)

    2010-09-30

    ...: Proposed Authorization of State Hazardous Waste Management Program Revision AGENCY: Environmental... its hazardous waste management program by November 1, 2010. ADDRESSES: Submit your comments... waste management program. EPA continues to have independent enforcement authority under RCRA sections...

  16. A Proposal to Build an Education Research and Development Program: The Kamehameha Early Education Project Proposal. Technical Report #3.

    Science.gov (United States)

    Gallimore, Ronald; And Others

    This report summarizes the programmatic features of a proposal for the Kamehameha Early Education Project (KEEP), a program aimed at the development, demonstration, and dissemination of methods for improving the education of Hawaiian and part-Hawaiian children. A brief description of the proposed project goals, structure, organization, and…

  17. PROGRESSIVE CHOICE PROGRAMMING FOR DELINQUENOGENIC COMMUNITIES, A PROPOSAL FOR RESEARCH.

    Science.gov (United States)

    Institute of Educational Research, Washington, DC.

    THE TWO MAJOR TARGET POPULATIONS FOR THESE PROGRAMS ARE CHILDREN ENTERING SCHOOL IN FIRST OR SECOND GRADE WHO ARE IN DELINQUENOGENIC NEIGHBORHOODS AND ADOLESCENT DROPOUTS WHO ATTEND SPECIAL YOUTH COUNSELING CENTERS WHERE SKILLS CAN BE TAUGHT. THE PROGRAM SHOULD DEVELOP READING SKILLS AND ENRICH VOCABULARY PROVIDING A BASIS FOR ACCELERATED…

  18. Professional skills training proposal for professors of health programs

    Directory of Open Access Journals (Sweden)

    Mauricio Alberto Ángel-Macías

    2017-10-01

    Conclusions: This study shows the urgent need for creating training spaces in pedagogy, didactics and evaluation. In consequence, a model that includes cognitive, methodological, social and personal skills is proposed.

  19. 77 FR 9216 - Native American Career and Technical Education Program; Proposed Waivers and Extension of the...

    Science.gov (United States)

    2012-02-16

    ... DEPARTMENT OF EDUCATION Native American Career and Technical Education Program; Proposed Waivers...) 2007 under the Native American Career and Technical Education Program (NACTEP), the Secretary proposes... secondary school career and technical education programs. \\1\\ Section 116(a)(2) of the Carl D. Perkins...

  20. 78 FR 23775 - Notice of Proposed Information Collection; Comment Request: Tax Credit Assistance Program (TCAP)

    Science.gov (United States)

    2013-04-22

    ... Information Collection; Comment Request: Tax Credit Assistance Program (TCAP) AGENCY: Office of the Chief... information: Title of Proposed: Tax Credit Assistance Program (TCAP). OMB Approval Number: 2506-0181. Form Numbers: None. Description of the need for the information and proposed use: Tax Credit Assistance Program...

  1. 75 FR 18873 - Notice of Proposed Information Collection: Youthbuild Program

    Science.gov (United States)

    2010-04-13

    .... The Youthbuild grant life cycle is approximately 30 months with approximately 86 currently active... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5377-N-01] Notice of Proposed... be sent to: Robert Duncan, Department of Housing Urban and Development, 451 7th Street, SW., Room...

  2. 77 FR 24766 - Call for Proposals for a Micro Support Program on International Conflict Resolution and...

    Science.gov (United States)

    2012-04-25

    ... UNITED STATES INSTITUTE OF PEACE Call for Proposals for a Micro Support Program on International Conflict Resolution and Peacebuilding For Immediate Release AGENCY: United States Institute of Peace. ACTION: Notice. SUMMARY: Micro Support Program on International Conflict Resolution and Peacebuilding...

  3. 76 FR 38198 - Notice of Submission of Proposed Information Collection to OMB Housing Counseling Program...

    Science.gov (United States)

    2011-06-29

    ... Proposed Information Collection to OMB Housing Counseling Program- Application for Approval as a Housing... private nonprofit agencies that provide housing counseling services directly or through their affiliates or branches regarding home buying, homeownership and rental housing programs submit an application...

  4. 77 FR 17458 - Proposed Information Collection; Comment Request; Observer Programs' Information that Can Be...

    Science.gov (United States)

    2012-03-26

    ... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Proposed Information Collection; Comment Request; Observer Programs' Information that Can Be Gathered Only Through Questions... options; and (5) ensure that the observer programs can safely and efficiently collect the information...

  5. A label-free electrochemiluminescent sensor for ATP detection based on ATP-dependent ligation.

    Science.gov (United States)

    Zhao, Tingting; Lin, Chunshui; Yao, Qiuhong; Chen, Xi

    2016-07-01

    In this work, we describe a new label-free, sensitive and highly selective strategy for the electrochemiluminescent (ECL) detection of ATP at the picomolar level via ATP-induced ligation. The molecular-beacon like DNA probes (P12 complex) are self-assembled on a gold electrode. The presence of ATP leads to the ligation of P12 complex which blocks the digestion by Exonuclease III (Exo III). The protected P12 complex causes the intercalation of numerous ECL indicators (Ru(phen)3(2+)) into the duplex DNA grooves, resulting in significantly amplified ECL signal output. Since the ligating site of T4 DNA ligase and the nicking site of Exo III are the same, it involves no long time of incubation for conformation change. The proposed strategy combines the amplification power of enzyme and the inherent high sensitivity of the ECL technique and enables picomolar detection of ATP. The developed strategy also shows high selectivity against ATP analogs, which makes our new label-free and highly sensitive ligation-based method a useful addition to the amplified ATP detection arena. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. 75 FR 36659 - Proposed Collection; Comment Request; Brain Power! The NIDA Junior Scientist Program and the...

    Science.gov (United States)

    2010-06-28

    ... of the Brain Power! Program's ability to: Increase students' knowledge about the biology of the brain... Request; Brain Power! The NIDA Junior Scientist Program and the Companion Program, Brain Power! Challenge.... Proposed Collection: Title: Brain Power! The NIDA Junior Scientist Program, for grades K-5, and the...

  7. 76 FR 18570 - Notice of Proposed Information Collection for Public Comment; HOPE VI Public Housing Programs...

    Science.gov (United States)

    2011-04-04

    ... Information Collection for Public Comment; HOPE VI Public Housing Programs: Funding and Program Data... responses. This Notice also lists the following information: Title of Proposal: HOPE VI program. OMB Control... (Pub. L. 105- 276, 112 Stat. 2461, approved October 21, 1998) and revised by the HOPE VI Program...

  8. R&D PROPOSAL FOR THE NATIONAL MUON ACCELERATOR PROGRAM

    OpenAIRE

    Zisman, Michael S.

    2011-01-01

    This document contains a description of a multi-year national R&D program aimed at completing a Design Feasibility Study (DFS) for a Muon Collider and, with international participation, a Reference Design Report (RDR) for a muon-based Neutrino Factory. It also includes the supporting component development and experimental efforts that will inform the design studies and permit an initial down-selection of candidate technologies for the ionization cooling and acceleration systems. We intend to ...

  9. Validation of a proposal for evaluating hospital infection control programs.

    Science.gov (United States)

    Silva, Cristiane Pavanello Rodrigues; Lacerda, Rúbia Aparecida

    2011-02-01

    To validate the construct and discriminant properties of a hospital infection prevention and control program. The program consisted of four indicators: technical-operational structure; operational prevention and control guidelines; epidemiological surveillance system; and prevention and control activities. These indicators, with previously validated content, were applied to 50 healthcare institutions in the city of São Paulo, Southeastern Brazil, in 2009. Descriptive statistics were used to characterize the hospitals and indicator scores, and Cronbach's α coefficient was used to evaluate the internal consistency. The discriminant validity was analyzed by comparing indicator scores between groups of hospitals: with versus without quality certification. The construct validity analysis was based on exploratory factor analysis with a tetrachoric correlation matrix. The indicators for the technical-operational structure and epidemiological surveillance presented almost 100% conformity in the whole sample. The indicators for the operational prevention and control guidelines and the prevention and control activities presented internal consistency ranging from 0.67 to 0.80. The discriminant validity of these indicators indicated higher and statistically significant mean conformity scores among the group of institutions with healthcare certification or accreditation processes. In the construct validation, two dimensions were identified for the operational prevention and control guidelines: recommendations for preventing hospital infection and recommendations for standardizing prophylaxis procedures, with good correlation between the analysis units that formed the guidelines. The same was found for the prevention and control activities: interfaces with treatment units and support units were identified. Validation of the measurement properties of the hospital infection prevention and control program indicators made it possible to develop a tool for evaluating these programs

  10. Preliminary proposal for a beryllium technology program for fusion applications

    International Nuclear Information System (INIS)

    1985-02-01

    The program was designed to provide the answers to the critical issues of beryllium technology needed in fusion blanket designs. The four tasks are as follows: (1) Beryllium property measurements needed for fusion data base. (2) Beryllium stress relaxation and creep measurements for lifetime modelling calculations. (3) Simplified recycle technique development for irradiated beryllium. (4) Beryllium neutron multiplier measurements using manganese bath absolute calibration techniques

  11. A Proposal for the Common Safety Approach of Space Programs

    Science.gov (United States)

    Grimard, Max

    2002-01-01

    For all applications, business and systems related to Space programs, Quality is mandatory and is a key factor for the technical as well as the economical performances. Up to now the differences of applications (launchers, manned space-flight, sciences, telecommunications, Earth observation, planetary exploration, etc.) and the difference of technical culture and background of the leading countries (USA, Russia, Europe) have generally led to different approaches in terms of standards and processes for Quality. At a time where international cooperation is quite usual for the institutional programs and globalization is the key word for the commercial business, it is considered of prime importance to aim at common standards and approaches for Quality in Space Programs. For that reason, the International Academy of Astronautics has set up a Study Group which mandate is to "Make recommendations to improve the Quality, Reliability, Efficiency, and Safety of space programmes, taking into account the overall environment in which they operate : economical constraints, harsh environments, space weather, long life, no maintenance, autonomy, international co-operation, norms and standards, certification." The paper will introduce the activities of this Study Group, describing a first list of topics which should be addressed : Through this paper it is expected to open the discussion to update/enlarge this list of topics and to call for contributors to this Study Group.

  12. Technical basis for the proposed high efficiency nuclear fuel program

    International Nuclear Information System (INIS)

    MacDonald, P.E.; Herring, J.S.; Crawford, D.C.; Neimark, L.E.

    1999-01-01

    Greenhouse gas emissions from fossil fired electricity generating stations will dramatically increase over the next 20 years. Nuclear energy is the only fully developed technology able to supply large amounts of electricity without generation of greenhouse gases. However, the problem of noncompetitive economics and public concerns about radioactive waste disposal, safety, and nuclear weapons proliferation may prevent the reemergence of nuclear power as a preferred option for new electric energy generation in the U.S. This paper discusses a new research program to help address these issues, by developing fuel designs capable of burnup values in excess of 60 MWD/kgU. The objectives of the program are to: improve the reliability and robustness of light water reactor fuel, thereby improving safety margins; Significantly increase the energy generated by each fuel loading, thereby achieving longer operating cycles, higher capacity factors, and lower cost electric power; Significantly reduce the volume of spent nuclear fuel discharged for disposal by allowing more energy to be extracted from each fuel element prior to discharge; Develop fuel that is much more proliferation resistant. (author)

  13. Impacts of the proposed program approach on waste stream characteristics

    International Nuclear Information System (INIS)

    King, J.F.; Fleming, M.E.

    1995-01-01

    The evolution of the U.S. Department of Energy's Civilian Radioactive Waste Management System (CRWMS) over the past few years has led to significant changes in key system scenario assumption. This paper describes the effects of two recent changes on waste stream characteristics focusing primarily on repository impacts. First, the multi-purpose canister (MPC) concept has been included in the Program baseline. The change from a bare fuel system to one including an MPC-based system forces the fuel assemblies initially loaded together in MPCs to remain together throughout the system. Second, current system analyses also assume a system without a monitored retrievable storage (MRS), with the understanding that an MRS would be reincorporated if a site becomes available. Together these two changes have significant impacts on waste stream characteristics. Those two changes create a class of scenarios referred to generally as Program Approach (PA) scenarios. Scenarios based on the previously assumed system, bare fuel with an MRS, are referred to here as the Previous Reference (PR) system scenarios. The analysis compares scenarios with otherwise consistent assumptions and presents summary comparisons. The number of disposal containers and the waste heat output are determined for eight PA and PR scenarios

  14. Lightning Protection Performance Assessment of Transmission Line Based on ATP model Automatic Generation

    Directory of Open Access Journals (Sweden)

    Luo Hanwu

    2016-01-01

    Full Text Available This paper presents a novel method to solve the initial lightning breakdown current by combing ATP and MATLAB simulation software effectively, with the aims to evaluate the lightning protection performance of transmission line. Firstly, the executable ATP simulation model is generated automatically according to the required information such as power source parameters, tower parameters, overhead line parameters, grounding resistance and lightning current parameters, etc. through an interface program coded by MATLAB. Then, the data are extracted from the generated LIS files which can be obtained by executing the ATP simulation model, the occurrence of transmission lie breakdown can be determined by the relative data in LIS file. The lightning current amplitude should be reduced when the breakdown occurs, and vice the verse. Thus the initial lightning breakdown current of a transmission line with given parameters can be determined accurately by continuously changing the lightning current amplitude, which is realized by a loop computing algorithm that is coded by MATLAB software. The method proposed in this paper can generate the ATP simulation program automatically, and facilitates the lightning protection performance assessment of transmission line.

  15. 77 FR 30305 - Notice of Proposed Information Collection; Comment Request Housing Counseling Program

    Science.gov (United States)

    2012-05-22

    ... Information Collection; Comment Request Housing Counseling Program AGENCY: Office of the Assistant Secretary... information: Title of Proposal: Housing Counseling Program. OMB Control Number, if applicable: 2502-0261. Description of the need for the information and proposed use: Nonprofit Housing Counseling organizations...

  16. 78 FR 70090 - 30-Day Notice of Proposed Information Collection: PEPFAR Program Expenditures

    Science.gov (United States)

    2013-11-22

    .... Summaries of these data provide key information about program costs under PEPFAR on a global level. Applying... Program Expenditures. OMB Control Number: 1405-0208. Type of Request: Revision of a currently approved... program monitoring, the Finance and Economics Work Group under PEPFAR proposes to add reporting of...

  17. Proposed Accreditation Standards for Degree-Granting Correspondence Programs Offered by Accredited Institutions.

    Science.gov (United States)

    McGraw-Hill Continuing Education Center, Washington, DC.

    A study on proposed accreditation standards grew out of a need to (1) stimulate the growth of quality correspondence degree programs; and (2) provide a policy for accreditation of correspondence degree programs so that graduates would be encouraged to pursue advanced degree programs offered elsewhere by educational institutions. The study focused…

  18. 76 FR 71037 - Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens: Request...

    Science.gov (United States)

    2011-11-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Proposed National Toxicology Program (NTP) Review Process...: Division of the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences.... Bucher, Associate Director, National Toxicology Program. [FR Doc. 2011-29615 Filed 11-15-11; 8:45 am...

  19. 77 FR 27253 - Proposed Collection, Laura Bush 21st Century Librarian Grant Program Evaluation

    Science.gov (United States)

    2012-05-09

    ... Century Librarian Grant Program Evaluation AGENCY: Institute of Museum and Library Services, National... evaluate and make improvements to the Laura Bush 21st Century Librarian (LB21) Grant Program. The... proposes clearance of the Laura Bush 21st Century Librarian Grant Program Evaluation. The 60-day Notice for...

  20. ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease.

    Science.gov (United States)

    Nakano, Masaki; Imamura, Hiromi; Sasaoka, Norio; Yamamoto, Masamichi; Uemura, Norihito; Shudo, Toshiyuki; Fuchigami, Tomohiro; Takahashi, Ryosuke; Kakizuka, Akira

    2017-08-01

    Parkinson's disease is assumed to be caused by mitochondrial dysfunction in the affected dopaminergic neurons in the brain. We have recently created small chemicals, KUSs (Kyoto University Substances), which can reduce cellular ATP consumption. By contrast, agonistic ligands of ERRs (estrogen receptor-related receptors) are expected to raise cellular ATP levels via enhancing ATP production. Here, we show that esculetin functions as an ERR agonist, and its addition to culture media enhances glycolysis and mitochondrial respiration, leading to elevated cellular ATP levels. Subsequently, we show the neuroprotective efficacies of KUSs, esculetin, and GSK4716 (an ERRγ agonist) against cell death in Parkinson's disease models. In the surviving neurons, ATP levels and expression levels of α-synuclein and CHOP (an ER stress-mediated cell death executor) were all rectified. We propose that maintenance of ATP levels, by inhibiting ATP consumption or enhancing ATP production, or both, would be a promising therapeutic strategy for Parkinson's disease. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. 76 FR 44306 - Proposed Information Collection; Comment Request; Fisheries Finance Program Requirements

    Science.gov (United States)

    2011-07-25

    ... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Proposed Information Collection; Comment Request; Fisheries Finance Program Requirements AGENCY: National Oceanic and Atmospheric Administration (NOAA), Commerce. ACTION: Notice. SUMMARY: The Department of Commerce, as part of its continuing...

  2. 75 FR 52393 - Proposed Data Collection; Comment Request: New Markets Tax Credit (NMTC) Program-Allocation...

    Science.gov (United States)

    2010-08-25

    ... DEPARTMENT OF THE TREASURY Community Development Financial Institutions Fund Proposed Data... Institutions (CDFI) Fund, Department of the Treasury, is soliciting comments concerning the New Markets Tax... comments to Rosa Martinez, Acting NMTC Program Manager, Community Development Financial Institutions Fund...

  3. ATP-dependent human RISC assembly pathways.

    Science.gov (United States)

    Yoda, Mayuko; Kawamata, Tomoko; Paroo, Zain; Ye, Xuecheng; Iwasaki, Shintaro; Liu, Qinghua; Tomari, Yukihide

    2010-01-01

    The assembly of RNA-induced silencing complex (RISC) is a key process in small RNA-mediated gene silencing. In humans, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are incorporated into RISCs containing the Argonaute (AGO) subfamily proteins Ago1-4. Previous studies have proposed that, unlike Drosophila melanogaster RISC assembly pathways, human RISC assembly is coupled with dicing and is independent of ATP. Here we show by careful reexamination that, in humans, RISC assembly and dicing are uncoupled, and ATP greatly facilitates RISC loading of small-RNA duplexes. Moreover, all four human AGO proteins show remarkably similar structural preferences for small-RNA duplexes: central mismatches promote RISC loading, and seed or 3'-mid (guide position 12-15) mismatches facilitate unwinding. All these features of human AGO proteins are highly reminiscent of fly Ago1 but not fly Ago2.

  4. Pilot program to assess proposed basic quality assurance requirements in the medical use of byproduct materials

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, E.; Nelson, K.; Meinhold, C.B. (Brookhaven National Lab., Upton, NY (United States))

    1991-10-01

    In January 1990, the Nuclear Regulatory Commission (NRC) proposed amendments to 10 CFR Part 35 that would require medical licensees using byproduct material to establish and implement a basic quality assurance program. A 60-day real-world trial of the proposed rules was initiated to obtain information beyond that generally found through standard public comment procedures. Volunteers from randomly selected institutions had opportunities to review the details of the proposed regulations and to implement these rules on a daily basis during the trial. The participating institutions were then asked to evaluate the proposed regulations based on their personal experiences. The pilot project sought to determine whether medical institutions could develop written quality assurance programs that would meet the eight performance-based objectives of proposed Section 35.35. In addition, the NRC wanted to learn from these volunteers if they had any recommendations on how the rule could be revised to minimized its cost and to clarify its objectives without decreasing its effectiveness. It was found that licensees could develop acceptable QA programs under a performance-based approach, that most licensee programs did meet the proposed objectives, and that most written QA plans would require consultations with NRC or Agreement State personnel before they would fully meet all objectives of proposed Section 35.35. This report describes the overall pilot program. The methodology used to select and assemble the group of participating licensees is presented. The various workshops and evaluation questionnaires are discussed, and detailed findings are presented. 7 refs.

  5. Pilot program to assess proposed basic quality assurance requirements in the medical use of byproduct materials

    International Nuclear Information System (INIS)

    Kaplan, E.; Nelson, K.; Meinhold, C.B.

    1991-10-01

    In January 1990, the Nuclear Regulatory Commission (NRC) proposed amendments to 10 CFR Part 35 that would require medical licensees using byproduct material to establish and implement a basic quality assurance program. A 60-day real-world trial of the proposed rules was initiated to obtain information beyond that generally found through standard public comment procedures. Volunteers from randomly selected institutions had opportunities to review the details of the proposed regulations and to implement these rules on a daily basis during the trial. The participating institutions were then asked to evaluate the proposed regulations based on their personal experiences. The pilot project sought to determine whether medical institutions could develop written quality assurance programs that would meet the eight performance-based objectives of proposed Section 35.35. In addition, the NRC wanted to learn from these volunteers if they had any recommendations on how the rule could be revised to minimized its cost and to clarify its objectives without decreasing its effectiveness. It was found that licensees could develop acceptable QA programs under a performance-based approach, that most licensee programs did meet the proposed objectives, and that most written QA plans would require consultations with NRC or Agreement State personnel before they would fully meet all objectives of proposed Section 35.35. This report describes the overall pilot program. The methodology used to select and assemble the group of participating licensees is presented. The various workshops and evaluation questionnaires are discussed, and detailed findings are presented. 7 refs

  6. 78 FR 31999 - 30-Day Notice of Proposed Information Collection: Iran Democracy Program Grants Vetting

    Science.gov (United States)

    2013-05-28

    ... DEPARTMENT OF STATE [Public Notice 8337] 30-Day Notice of Proposed Information Collection: Iran Democracy Program Grants Vetting ACTION: Notice of request for public comment and submission to OMB of proposed collection of information. SUMMARY: The Department of State has submitted the information...

  7. 77 FR 29647 - Medicare Program; Solicitation for Proposals for the Medicare Graduate Nurse Education...

    Science.gov (United States)

    2012-05-18

    ...] Medicare Program; Solicitation for Proposals for the Medicare Graduate Nurse Education Demonstration... participate in the Medicare Graduate Nurse Education (GNE) Demonstration. DATES: Proposals will be considered...--(A) 1 or more applicable schools of nursing; and (B) 2 or more applicable non- hospital community...

  8. 76 FR 22411 - Notice of Proposed Information Collection: Comment Request; Housing Counseling Program...

    Science.gov (United States)

    2011-04-21

    ... Information Collection: Comment Request; Housing Counseling Program--Application for Approval as a Housing Counseling Agency AGENCY: Office of the Assistant Secretary for Housing, HUD. ACTION: Notice. SUMMARY: The...: Title of Proposal: Housing Counseling Program--Application for Approval as a Housing Counseling Agency...

  9. 77 FR 61776 - Notice of Submission of Proposed Information Collection to OMB Housing Counseling Program

    Science.gov (United States)

    2012-10-11

    ... Proposed Information Collection to OMB Housing Counseling Program AGENCY: Office of the Assistant Secretary... Housing Counseling Program and reference to the NOFA charts were excluded. Nonprofit Housing Counseling... provide housing counseling assistance to eligible homebuyers to find and purchase affordable housing...

  10. 78 FR 12349 - Proposed Information Collection; Land and Water Conservation Fund State Assistance Program

    Science.gov (United States)

    2013-02-22

    ...] Proposed Information Collection; Land and Water Conservation Fund State Assistance Program AGENCY: National.... Abstract The Land and Water Conservation Fund Act of 1965 (LWCF Act) (16 U.S.C. 460l-4 et seq.) was enacted... discussed in detail in the Land and Water Conservation Fund State Assistance Program Federal Financial...

  11. 76 FR 67200 - Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens: Request...

    Science.gov (United States)

    2011-10-31

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed National Toxicology... Session AGENCY: Division of the National Toxicology Program (DNTP), National Institute of Environmental.... Bucher, Associate Director, National Toxicology Program. [FR Doc. 2011-28132 Filed 10-28-11; 8:45 am...

  12. Program grants for black lung clinics--PHS. Notice of proposed rulemaking.

    Science.gov (United States)

    1983-11-01

    The Public Health Service proposed to revise the regulations governing the grants program for black lung clinics established under section 427(a) of the Federal Mine Safety and Health Act of 1977. The revision is in keeping with the Department of Health and Human Services' desire to remove as many programmatic burdens and restrictions from grantees as possible, while maintaining program integrity.

  13. 76 FR 21372 - Medicare Program; Solicitation for Proposals for the Medicare Community-Based Care Transitions...

    Science.gov (United States)

    2011-04-15

    ...] Medicare Program; Solicitation for Proposals for the Medicare Community-Based Care Transitions Program... interested parties of an opportunity to apply to participate in the Medicare Community-based Care Transitions.... 111-148, enacted on March 23, 2010) (Affordable Care Act) authorized the Medicare Community-based Care...

  14. 75 FR 78939 - Senior Community Service Employment Program; Notice of Proposed Rulemaking, Additional Indicator...

    Science.gov (United States)

    2010-12-17

    ... Community Service Employment Program; Notice of Proposed Rulemaking, Additional Indicator on Volunteer Work... Senior Community Service Employment Program (SCSEP), Additional Indicator on Volunteer Work that was... number of exiting participants who enter volunteer work. The relevant Office of Management and Budget...

  15. 77 FR 13619 - Notice of Submission of Proposed Information Collection to OMB; Housing Choice Voucher Program

    Science.gov (United States)

    2012-03-07

    ... Proposed Information Collection to OMB; Housing Choice Voucher Program AGENCY: Office of the Chief... assistance payments, and budget and payment documentation. In some cases, PHAs voluntarily divest their voucher programs to a receiving PHA. PHAs may also project-base a portion of their vouchers or use their...

  16. 75 FR 55596 - Notice of Submission of Proposed Information Collection to OMB Housing Choice Voucher Program

    Science.gov (United States)

    2010-09-13

    ... Proposed Information Collection to OMB Housing Choice Voucher Program AGENCY: Office of the Chief... assistance payments, and budget and payment documentation. In some cases PHAs voluntarily divest their voucher programs to a receiving PHA. PHAs may also project-base a portion of their vouchers or use their...

  17. Label free luminescence strategy for sensitive detection of ATP using aptamer-Ru(II) complexes

    Energy Technology Data Exchange (ETDEWEB)

    Babu, Eththilu [Department of Physical Che mistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, Tamil Nadu (India); Muthu Mareeswaran, Paulpandian [Department of Physical Che mistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, Tamil Nadu (India); Department of Industrial Chemistry, Alagappa Univesity, Karaikudi 630003, Tamil Nadu (India); Ramdass, Arumugam [Department of Physical Che mistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, Tamil Nadu (India); Research Department of Chemistry, Aditanar College of Arts and Science, Tiruchendur 628216, Tamil Nadu (India); Ramesh, Pandian [UCIBIO-REQUIMTE, Departmento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica (Portugal); Rajagopal, Seenivasan, E-mail: rajagopalseenivasan@yahoo.com [Department of Physical Che mistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, Tamil Nadu (India)

    2016-07-15

    A simple and sensitive aptamer-based luminescence strategy for ATP detection is developed using Ru(II) complexes as probe molecule. It is based on the fact that Ru(II)-dppz complexes show the light switching behavior with DNA aptamers and found to show significant luminescence spectral change on the addition of ATP molecules. The binding efficiencies of aptamer with ATP, ADP and AMP are calculated and compared. The structural change of aptamer is also studied using circular dichroism (CD) spectral techniques. Moreover, the binding nature of aptamer with ATP, ADP and AMP is demonstrated by computational techniques. The proposed strategy was successfully applied to the detection of ATP.

  18. Label free luminescence strategy for sensitive detection of ATP using aptamer-Ru(II) complexes

    International Nuclear Information System (INIS)

    Babu, Eththilu; Muthu Mareeswaran, Paulpandian; Ramdass, Arumugam; Ramesh, Pandian; Rajagopal, Seenivasan

    2016-01-01

    A simple and sensitive aptamer-based luminescence strategy for ATP detection is developed using Ru(II) complexes as probe molecule. It is based on the fact that Ru(II)-dppz complexes show the light switching behavior with DNA aptamers and found to show significant luminescence spectral change on the addition of ATP molecules. The binding efficiencies of aptamer with ATP, ADP and AMP are calculated and compared. The structural change of aptamer is also studied using circular dichroism (CD) spectral techniques. Moreover, the binding nature of aptamer with ATP, ADP and AMP is demonstrated by computational techniques. The proposed strategy was successfully applied to the detection of ATP.

  19. Keragaman Genetik Sekuen Gen ATP Synthase FO Subunit 6 (ATP6 Monyet Hantu (Tarsius Indonesia (GENETIC DIVERSITY STUDY OF ATP6 GENE SEQUENCES OF TARSIERS FROM INDONESIA

    Directory of Open Access Journals (Sweden)

    Rini Widayanti

    2013-07-01

    Full Text Available In a conservation effort, the identification of Tarsier species, on the bases of the morphological andmolecular characteristic is necessary. Up to now, the identification of the animals were based on themorphology and vocalizations, which is extremely difficult to identify each, tarsier species. The objective ofthis research was to study the genetic diversity on ATP6 gene of Tarsius sp. Based on sequencing of PCRproduct using primer ATP6F and ATP6R with 681 nts. PCR product. The sequence of ATP6 fragmentswere aligned with other primates from Gene bank with aid of software Clustal W, and were analyzed usingMEGA program version 4.0. Three different nucleotide sites were found (nucleotide no. 288, 321 and 367.The genetic distance based on nucleotide ATP6 sequence calculated using Kimura 2-parameter modelindicated that the smallest genetic distance 0%, biggest 0.8% and average 0, 2%. The phylogenetic treeusing neighbor joining method based on the sequence of nucleotide ATP6 gene could not be used todifferentiate among T. Dianae (from Central Sulawesi, T. Spectrum (from North Sulawesi, T. bancanus(from lampung, South Sumatera and T.bancanus from West Kalimantan.

  20. An ATP synthase harboring an atypical γ-subunit is involved in ATP synthesis in tomato fruit chromoplasts.

    Science.gov (United States)

    Pateraki, Irini; Renato, Marta; Azcón-Bieto, Joaquín; Boronat, Albert

    2013-04-01

    Chromoplasts are non-photosynthetic plastids specialized in the synthesis and accumulation of carotenoids. During fruit ripening, chloroplasts differentiate into photosynthetically inactive chromoplasts in a process characterized by the degradation of the thylakoid membranes, and by the active synthesis and accumulation of carotenoids. This transition renders chromoplasts unable to photochemically synthesize ATP, and therefore these organelles need to obtain the ATP required for anabolic processes through alternative sources. It is widely accepted that the ATP used for biosynthetic processes in non-photosynthetic plastids is imported from the cytosol or is obtained through glycolysis. In this work, however, we show that isolated tomato (Solanum lycopersicum) fruit chromoplasts are able to synthesize ATP de novo through a respiratory pathway using NADPH as an electron donor. We also report the involvement of a plastidial ATP synthase harboring an atypical γ-subunit induced during ripening, which lacks the regulatory dithiol domain present in plant and algae chloroplast γ-subunits. Silencing of this atypical γ-subunit during fruit ripening impairs the capacity of isolated chromoplast to synthesize ATP de novo. We propose that the replacement of the γ-subunit present in tomato leaf and green fruit chloroplasts by the atypical γ-subunit lacking the dithiol domain during fruit ripening reflects evolutionary changes, which allow the operation of chromoplast ATP synthase under the particular physiological conditions found in this organelle. © 2013 The Authors The Plant Journal © 2013 Blackwell Publishing Ltd.

  1. Striking a Balance between Program Requirements and GT Principles: Writing a compromised GT proposal

    Directory of Open Access Journals (Sweden)

    Sherry L. Xie, Ph.D. Candidate

    2009-06-01

    Full Text Available Glaser’s term “compromised GT proposal” (2001, p.114 refers to the type of Grounded Theory (GT proposal that is written in order to conform to the requirements of a standardized qualitative research proposal. A GT proposal needs only to supply information on the area of interest, the data source and a statement of method to the effect that the researcher begin to collect, code and analyse the data and let the theory emerge. Thus, the proposal may only occupy “a page or two” (Glaser, 2001, p. 111. Whilst being consistent with the methodology, a GT proposal sometimes has to give way to the format specified by a PhD program or committee even though the format was not defined for a GT proposal and in some areas, conflicts with GT principles; for example, the format may require a literature review. This short paper reports on my experience of writing a compromised GT proposal as a first-time GT researcher. It describes how both Glaser’s advice on writing compromised GT research proposals and the characteristics of the substantive area of the proposed research were used to satisfy program requirements while still maintaining GT fundamentals.

  2. 78 FR 59666 - Transmission Infrastructure Program; Proposed Transmission Infrastructure Program Updates and...

    Science.gov (United States)

    2013-09-27

    ... the Program to evaluate its current project development and financing practices and to identify areas... the conditions precedent required for a Project Applicant to apply for financing. Submitted after... involves the underwriting, financing, and loan monitoring and servicing for an Eligible Project. With few...

  3. Outline of research proposals selected in the Nuclear Energy Research Initiative (NERI) program

    International Nuclear Information System (INIS)

    Iwamura, Takamichi; Okubo, Tsutomu; Usui, Shuji

    1999-08-01

    The U.S. Department of Energy (DOE) created a new R and D program called Nuclear Energy Research Initiative (NERI)' in FY 1999 with the appropriation of $19 million. The major objectives of the NERI program is to preserve the nuclear science and engineering infrastructure in the U.S. and to maintain a competitive position in the global nuclear market in the 21st century. In may, 1999, the DOE selected 45 research proposals for the first year of the NERI program. The proposals are classified into the following five R and D areas: Proliferation Resistant Reactors and/or Fuel Cycles, New Reactor Designs, Advanced Nuclear Fuel, New Technology for Management of Nuclear Waste, Fundamental Nuclear Science. Since the NERI is a very epoch-making and strategic nuclear research program sponsored by the U.S. government, the trend of the NERI is considered to affect the future R and D programs in Japanese nuclear industries and research institutes including JAERI. The present report summarizes the analyzed results of the selected 45 research proposals. Staffs comments are made on each proposal in connection with the R and D activities in JAERI. (author)

  4. The relative influence of secondary versus primary prevention using the national cholesterol education program adult treatment panel II guidelines

    NARCIS (Netherlands)

    Goldman, L; Coxson, P; Hunink, MGM; Goldman, PA; Tosteson, ANA; Mittleman, M; Williams, L; Weinstein, MC

    OBJECTIVES This study was undertaken to project the population-wide effect of full implementation of the Adult Treatment Panel (ATP) II guidelines of the National Cholesterol Education Program (NCEP). BACKGROUND The ATP II has proposed guidelines for cholesterol reduction, but the long-term

  5. How To Prepare Program Proposals for the American Psychological Association Annual Convention.

    Science.gov (United States)

    Tentoni, Stuart C.

    The purpose of this paper is to dispel myths about preparing program proposals for the American Psychological Association's annual convention. The report's goal is to increase the number of student presenters at future annual conventions. It has been determined that, for a variety of reasons, psychology graduate students participate more in poster…

  6. 77 FR 43560 - American Indian Vocational Rehabilitation Services Program; Proposed Waivers and Extensions of...

    Science.gov (United States)

    2012-07-25

    ... Program; Proposed Waivers and Extensions of the Project Periods AGENCY: Office of Special Education and... rehabilitation services to American Indians with disabilities who reside on or near Federal or State reservations... documents published by the Department. Dated: July 19, 2012. Alexa Posny, Assistant Secretary for Special...

  7. 77 FR 57103 - Notice of Submission of Proposed Information Collection to OMB Housing Counseling Program

    Science.gov (United States)

    2012-09-17

    ... Proposed Information Collection to OMB Housing Counseling Program AGENCY: Office of the Chief Information... Counseling organizations submit information to HUD through Grants.gov when applying for grant funds to provide housing counseling assistance to eligible homebuyers to find and purchase affordable housing...

  8. 78 FR 79638 - Energy Conservation Program for Consumer Products: Proposed Determination of Hearth Products as a...

    Science.gov (United States)

    2013-12-31

    ... Conservation Program for Consumer Products: Proposed Determination of Hearth Products as a Covered Consumer... determined that hearth products qualify as a covered product under Part A of Title III of the Energy Policy and Conservation Act (EPCA), as amended. More specifically, DOE has tentatively determined that hearth...

  9. 75 FR 11327 - Proposed Establishment of Certification Programs for Health Information Technology

    Science.gov (United States)

    2010-03-10

    ... Certification Programs for Health Information Technology; Proposed Rule #0;#0;Federal Register / Vol. 75, No. 46... for Health Information Technology AGENCY: Office of the National Coordinator for Health Information... granted to the National Coordinator for Health Information Technology (the National Coordinator) by...

  10. 76 FR 34633 - Medicare Program; Proposed Changes to the Hospital Inpatient Prospective Payment Systems for...

    Science.gov (United States)

    2011-06-14

    ..., 413, and 476 [CMS-1518-CN] RIN 0938-AQ24 Medicare Program; Proposed Changes to the Hospital Inpatient...-9644 of May 5, 2011 (76 FR 25788), there were a number of technical and typographical errors that are...) endorsement number for the CMS quality measure, Percent of Residents With Pressure Ulcers That Are New or...

  11. 77 FR 13619 - Notice of Proposed Information for Public Comment for: Public Housing Capital Fund Program

    Science.gov (United States)

    2012-03-07

    ... that are not subject to Independent Public Accountant (IPA) audit requirements. Agency form numbers, if... Information for Public Comment for: Public Housing Capital Fund Program AGENCY: Office of the Assistant Secretary for Public and Indian Housing, HUD. ACTION: Notice. SUMMARY: The proposed information collection...

  12. Communicative Competence of the Fourth Year Students: Basis for Proposed English Language Program

    Science.gov (United States)

    Tuan, Vu Van

    2017-01-01

    This study on level of communicative competence covering linguistic/grammatical and discourse has aimed at constructing a proposed English language program for 5 key universities in Vietnam. The descriptive method utilized was scientifically employed with comparative techniques and correlational analysis. The researcher treated the surveyed data…

  13. 75 FR 72830 - Medicare Program; Quality Improvement Organization (QIO) Contracts: Solicitation of Proposals...

    Science.gov (United States)

    2010-11-26

    ...] Medicare Program; Quality Improvement Organization (QIO) Contracts: Solicitation of Proposals From In-State... the Social Security Act (the Act) to provide at least 6 months' advance notice of the expiration dates of contracts with out- of-State Quality Improvement Organizations (QIOs) before renewing any of those...

  14. 78 FR 15798 - 60-Day Notice of Proposed Information Collection: Iran Democracy Program Grants Vetting

    Science.gov (United States)

    2013-03-12

    ... DEPARTMENT OF STATE [Public Notice 8218] 60-Day Notice of Proposed Information Collection: Iran Democracy Program Grants Vetting ACTION: Notice of request for public comment. SUMMARY: The Department of State is seeking Office of Management and Budget (OMB) approval for the information collection described...

  15. Existing and Proposed Child Find Initiatives in One State's Part C Program

    Science.gov (United States)

    Edwards, Nicole Megan; Gallagher, Peggy A.; Green, Katherine B.

    2013-01-01

    Despite a Child Find mandate in IDEA, early detection and screening of infants and toddlers with special needs continues to remain an area in need of improvement. The authors sought to better understand existing and proposed outreach initiatives in one state's Part C Early Intervention (EI) program that ranks among the lowest nationally in the…

  16. 76 FR 29747 - State Program Requirements; Proposal To Approve Maine's Base National Pollutant Discharge...

    Science.gov (United States)

    2011-05-23

    ... of cooling water intake structures under CWA section 316(b). Authority: This action is proposed to be... the First Circuit vacated EPA's October 31, 2003 decision to withhold the permitting of two tribally..., 1999). Maine's application included an assertion of authority to implement the program in the...

  17. Guidelines For Implementation of Industrial Programs For Proposed Community Colleges in Venezuela.

    Science.gov (United States)

    Sada, Pablo Maria

    The purpose of this study was to examine selected industrial education departments and programs of the community colleges in the United States, and to draw some beneficial implications for the establishment of the proposed community colleges in Venezuela. The procedure involved a review of the literature, the construction of a questionnaire, and…

  18. 77 FR 16841 - Medicare Program; Solicitation for Proposals for the Medicare Graduate Nurse Education...

    Science.gov (United States)

    2012-03-22

    ...] Medicare Program; Solicitation for Proposals for the Medicare Graduate Nurse Education Demonstration... Education (GNE) Demonstration. The primary goal of the GNE Demonstration is to increase the number of... schools of nursing; and (B) 2 or more applicable non-hospital community-based care settings. The written...

  19. Proposal of Modification Strategy of NC Program in the Virtual Manufacturing Environment

    Science.gov (United States)

    Narita, Hirohisa; Chen, Lian-Yi; Fujimoto, Hideo; Shirase, Keiichi; Arai, Eiji

    Virtual manufacturing will be a key technology in process planning, because there are no evaluation tools for cutting conditions. Therefore, virtual machining simulator (VMSim), which can predict end milling processes, has been developed. The modification strategy of NC program using VMSim is proposed in this paper.

  20. 78 FR 79654 - Vermont: Proposed Authorization of State Hazardous Waste Management Program Revisions

    Science.gov (United States)

    2013-12-31

    ...] Vermont: Proposed Authorization of State Hazardous Waste Management Program Revisions AGENCY... Docket ID No. EPA-R01- RCRA-2013-0554, by mail to Sharon Leitch, RCRA Waste Management and UST Section..., RCRA Waste Management and UST Section, Office of Site Remediation and Restoration (OSRR07-1), US EPA...

  1. The Abbott School Construction Program: NJ Department of Education Proposed Facilities Regulations. Analysis of Preschool Issues

    Science.gov (United States)

    Ponessa, Joan; Boylan, Ellen

    2004-01-01

    This report on preschool facilities analyzes regulations proposed by the New Jersey Department of Education (NJDOE) to implement the Educational Facilities Construction and Financing Act. (EFCFA). EFCFA, which authorizes and governs New Jersey's public school construction program, was enacted in July 2000 to implement the State Supreme Court's…

  2. The Proposed Model of Collaborative Virtual Learning Environment for Introductory Programming Course

    Science.gov (United States)

    Othman, Mahfudzah; Othman, Muhaini

    2012-01-01

    This paper discusses the proposed model of the collaborative virtual learning system for the introductory computer programming course which uses one of the collaborative learning techniques known as the "Think-Pair-Share". The main objective of this study is to design a model for an online learning system that facilitates the…

  3. Persistence of the mitochondrial permeability transition in the absence of subunit c of human ATP synthase.

    Science.gov (United States)

    He, Jiuya; Ford, Holly C; Carroll, Joe; Ding, Shujing; Fearnley, Ian M; Walker, John E

    2017-03-28

    The permeability transition in human mitochondria refers to the opening of a nonspecific channel, known as the permeability transition pore (PTP), in the inner membrane. Opening can be triggered by calcium ions, leading to swelling of the organelle, disruption of the inner membrane, and ATP synthesis, followed by cell death. Recent proposals suggest that the pore is associated with the ATP synthase complex and specifically with the ring of c-subunits that constitute the membrane domain of the enzyme's rotor. The c-subunit is produced from three nuclear genes, ATP5G1 , ATP5G2 , and ATP5G3 , encoding identical copies of the mature protein with different mitochondrial-targeting sequences that are removed during their import into the organelle. To investigate the involvement of the c-subunit in the PTP, we generated a clonal cell, HAP1-A12, from near-haploid human cells, in which ATP5G1 , ATP5G2 , and ATP5G3 were disrupted. The HAP1-A12 cells are incapable of producing the c-subunit, but they preserve the characteristic properties of the PTP. Therefore, the c-subunit does not provide the PTP. The mitochondria in HAP1-A12 cells assemble a vestigial ATP synthase, with intact F 1 -catalytic and peripheral stalk domains and the supernumerary subunits e, f, and g, but lacking membrane subunits ATP6 and ATP8. The same vestigial complex plus associated c-subunits was characterized from human 143B ρ 0 cells, which cannot make the subunits ATP6 and ATP8, but retain the PTP. Therefore, none of the membrane subunits of the ATP synthase that are involved directly in transmembrane proton translocation is involved in forming the PTP.

  4. Effect of ATP sulfurylase overexpression in bright yellow 2 tobacco cells: regulation of ATP sulfurylase and SO4(-2) transport activities

    International Nuclear Information System (INIS)

    Hatzfeld, Y.; Cathala, N.; Grignon, C.; Davidian, J.C.

    1998-01-01

    To determine if the ATP sulfurylase reaction is a regulatory step for the SO4(2-)-assimilation pathway in plants, an Arabidopsis thaliana ATP sulfurylase cDNA, APS2, was fused to the 355 promoter of the cauliflower mosaic virus and introduced by Agrobacterium tumefaciens-mediated transformation into isolated Bright Yellow 2 tobacco (Nicotiana tabacum) cells. The ATP sulfurylase activity in transgenic cells was 8-fold that in control cells, and was correlated with the expression of a specific polypeptide revealed by western analysis using an anti-ATP sulfurylase antibody. The molecular mass of this polypeptide agreed with that for the overexpressed mature protein. ATP sulfurylase overexpression had no effect on [35S]SO4(2-) influx or ATP sulfurylase activity regulation by S availability, except that ATP sulfurylase activity variations in response to S starvation in transgenic cells were 8 times higher than in the wild type. There were also no differences in cell growth or sensitivity to SeO4(2-) (a toxic SO4(2-) analog) between transgenic and wild-type cells. We propose that in Bright Yellow 2 tobacco cells, the ATP sulfurylase derepression by S deficiency may involve a posttranscriptional mechanism, and that the ATP sulfurylase abundance is not limiting for cell metabolism

  5. An assessment of the water management program proposed in the Ranger EIS and its environmental implications

    International Nuclear Information System (INIS)

    Davy, D.R.

    1976-01-01

    An assessment of the water management program proposed in the Ranger EIS has three components: a) a statement of water quality criteria and standards that the program must meet, b) a set of calculations based on the best available estimates, that compares the expected levels of waste with the standards set for the release, c) the plan of the surveillance program aimed at demonstrating compliance with these standards and at revealing deficiencies in the choice of criteria, the derivation of standards from them and unforseen departures from expectation. Standards are suggested for the operation of the Ranger mines based on the most restrictive criterion out of: (i) acute toxicity tests carried out on organisms and water from the Magela Creek combined with application factors recommended by AWRC, (ii) the results on indicator species and biological diversity indices for the Finniss river, (iii) requirements for agricultural and pastoral use, (iv) the requirements for portable water. It is expected that the program proposed by Ranger will meet these standards and it is concluded that planning for a comprehensive environmental program is adequate. (author)

  6. Extracellular ATP induces albuminuria in pregnant rats

    NARCIS (Netherlands)

    Faas, M.M.; van der Schaaf, G.; Borghuis, T.; Jongman, R.M.; van Pampus, Maria; de Vos, P.; van Goor, Harry; Bakker, W.W.

    BACKGROUND: As circulating plasma ATP concentrations are increased in pre-eclampsia, we tested whether increased plasma ATP is able to induce albuminuria during pregnancy. METHODS: Pregnant (day 14) and non-pregnant rats were infused with ATP (3000 microg/kg bw) via a permanent jugular vein cannula.

  7. ATP Release and Effects in Pancreas

    DEFF Research Database (Denmark)

    Novak, Ivana; Amstrup, Jan; Henriksen, Katrine Lütken

    2003-01-01

    ATP and other nucleotides are released from various cells, but the pathway and physiological stimulus for ATP release are often unclear. The focus of our studies is the understanding of ATP release and signaling in rat exocrine pancreas. In acinar suspension mechanical stimulation, hypotonic shock...

  8. Draft report: a selection methodology for LWR safety R and D programs and proposals

    Energy Technology Data Exchange (ETDEWEB)

    Husseiny, A. A.; Ritzman, R. L.

    1980-03-01

    The results of work done to develop a methodology for selecting LWR safety R and D programs and proposals is described. A critical survey of relevant decision analysis methods is provided including the specifics of multiattribute utility theory. This latter method forms the basis of the developed selection methodology. Details of the methodology and its use are provided along with a sample illustration of its application.

  9. Environmental program planning for the proposed high-level nuclear waste repository at Yucca Mountain, Nevada

    International Nuclear Information System (INIS)

    1987-08-01

    This report was prepared to illustrate the policy and actions that the State of Nevada believe are required to assure that the quality of the environment is adequately considered during the course of the DOE work at the proposed high-level nuclear waste repository at Yucca Mountain. The report describes the DOE environmental program and the studies planned by NWPO to reflect the State's position toward environmental protection. 41 refs., 2 figs., 11 tabs

  10. Draft report: a selection methodology for LWR safety R and D programs and proposals

    International Nuclear Information System (INIS)

    Husseiny, A.A.; Ritzman, R.L.

    1980-03-01

    The results of work done to develop a methodology for selecting LWR safety R and D programs and proposals is described. A critical survey of relevant decision analysis methods is provided including the specifics of multiattribute utility theory. This latter method forms the basis of the developed selection methodology. Details of the methodology and its use are provided along with a sample illustration of its application

  11. 43 CFR 404.51 - Are proposed projects under the Rural Water Supply Program reviewed by the Administration?

    Science.gov (United States)

    2010-10-01

    ... Water Supply Program reviewed by the Administration? 404.51 Section 404.51 Public Lands: Interior... SUPPLY PROGRAM Feasibility Studies § 404.51 Are proposed projects under the Rural Water Supply Program... the Reclamation's Rural Water Supply Program. This includes review under Executive Order 12322 to...

  12. Proposal on application of Russian technical facilities for International Mars Research Program for 2009 2015

    Science.gov (United States)

    Polishchuk, Georgy; Pichkhadze, Konstantin; Vorontsov, Victor; Pavel, Kazmerchuk

    2006-07-01

    Recently International Mars Research Program is widely discussed. Well-known initiative of President of the USA, recent progress of American and European scientists and engineers in implementation of “Mars Odyssey” and “Mars-Express” projects and Russian proposals on cooperation and participation in “Phobos Sample Return” mission declare every intention to join efforts in the ambitious Martian Program realization. The final goal of the program for nearly 15 20 years is landing of a man on the Martian surface. Before this event happens another critical stage will be Martian soil sample return. Within the next 10 years, apparently, a major task will be scale research by means of various types of technical facilities. A crucial issue for this research will be creation of research station network which would allow collecting information about planetary conditions at far-remote points. By this time within the frame of “Phobos Sample Return Program” to be launched in 2009 it is planned to deliver some meteorological mini-landers developed by the Russian and Finnish specialists on the Martian surface. From this point view it is also interesting to use balloons capable to cover considerable distance. Such proposals have been made by Russian side for “Scout” mission. European “Aurora” program also anticipates application of wide range of technical means to explore the Martian atmosphere and surface including inflatable devices. Thus, for the International Mars Exploration Program, it seems to be very prospective to use apart from launch vehicles, upper stages etc. such technical means as mini-stations, Mars rovers, penetrators, balloons, etc.

  13. Making didactics proposals aimed at improving socioeducational programs for youngters at risk of social exclusion

    Directory of Open Access Journals (Sweden)

    María Violeta Álvarez Fernández

    2013-12-01

    Full Text Available Educators at Sograndio Juvenile Detention Center in Asturias were sure that they were able to offer new alternatives to improve their socio-educational intervention. That is the reason why they got involved in an action research training process aimed at making didactic proposals which tried to optimize the development of social competence programs for youngsters with criminal behavior. In order to do this, the Short Version of the Prosocial Thinking Program for Young People (Alba et al., 2005 was applied to nine inmates, eight males between 14 and 20 years old and a female of 16 years old. Theywere the basis and reflection of ourmethodological intervention. The teamtaking part in this intervention is formed by nine inmates and three external members (two coordinators and a woman psychologist. The investigation, mainly qualitative, includes different instruments (both qualitative and quantitative, such as: observation registries, discussion groups, questionnaires and notebooks. After the implementation of the program, positive changes must be highlighted in the emotional dimension, the resolution of problems, self-control and frustration tolerance. Besides, very high levels of satisfaction have been observed among youngsters, educators and external informants. It is important to have created a climate of professional compromise towards change and this way to have abandoned a passive attitude towards training, so that we were able to start an active search for practical answers, adjusted to our necessities and professional interests. Finally, we make several observations and intervention proposals that contribute to generate didactic knowledge thought and adapted for social education.

  14. New control method of on-board ATP system of Shinkansen trains

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, N.; Watanabe, T. [Railway Technical Research Inst. (Japan)

    2000-07-01

    We studied a new control method of the on-board automatic train protection (ATP) system for Shinkansen trains to shorten the operation time and not to degrade ride comfort at changes in deceleration of the train, while maintaining the safety and reliability of the present ATP signal system. We propose a new on-board pattern brake control system based on the present ATP data without changing the wayside equipment. By simulating the ATP braking of the proposed control method, we succeeded in shortening the operation time by 48 seconds per one station in comparison with the present ATP brake control system. This paper reports the concept of the system and simulation results of the on-board pattern. (orig.)

  15. Proposal to introduce Disaster Risk Management topics in Master programs in ESAN Graduate School of Business

    Directory of Open Access Journals (Sweden)

    CECILIA DEJO ESTEVES

    Full Text Available This paper aims to explain and present a proposal to introduce Disaster Risk Management (DRM topics into ESAN Graduate School of Business Master's programs. Although disasters have cost Peru more than USD 7,600 million in the past 2 decades the business sector, particularly Small and Medium Enterprises, have not developed preventive or continuity plans mainly because they are not familiar with DRM topics. Taking this into consideration, the paper presents a detailed academic/curricular proposal for DRM topics such as business continuity, business ethics, corporate social responsibility, and sustainable management. Additionally, it introduces the idea of promoting Disaster Risk Management (DRM topics to the Peruvian business community as a strategy to enhance the graduate education.

  16. Curricular renovation in the phonoaudiology program of the University of Cauca: a proposal for educational quality

    Directory of Open Access Journals (Sweden)

    Liliana María Pérez-Tenorio

    2010-09-01

    Full Text Available In Colombia, the Superior Education is going through a transformation process. These changes must be in coherence with the formulation of flexible policies among the diverse components of the curriculum and with the need for new forms of working and producing knowledge. The curricular renovation must ref lect an educational quality compromise and contribute to generate human development with high social impact. This article presents a proposal for Curricular Renovation, elaborated by faculty and students of the Phonoaudiology Program of the University of Cauca. This document contains aspects related to the pedagogic model, didactics, faculty-student relation, systems of evaluation and plan of studies. Furthermore, in this document the bases for the Route of Curricular Renovation are presented, consisting of the following phases: background, diagnosis and operational plan. These should facilitate the academic integration for adjusting the curricular processes to the needs of the academic program in a local, national and international context.

  17. Intertechnology Corporation proposed test and evaluation plan, commercial buildings. National Solar Demonstration Program

    Energy Technology Data Exchange (ETDEWEB)

    None

    1976-09-01

    This report has three major parts. The first of these derives the requirements for the Test and Evaluation plan from the System Level Plan which is summarized in Section II. The second part contains the proposed plan to fill these requirements and includes hardware and software recommendations as well as procedures and management considerations. Primary emphasis has been given to the remote site because this is the area in which the commercial part of the demonstration is most unique. Finally, some pre-demonstration activities are described. The pilot program is intended to resolve a number of issues which arose in the course of the T and E plan. These relate to choice of scan frequencies, compression algorithms, etc. It is also intended to confirm performance and cost effectiveness of the site data collection package. The base line measurements of attitudes, etc. provide a reference mark against which one can measure the non-technical effectiveness of the demonstration program. (WDM)

  18. General Electric Company proposed test and evaluation plan, commercial buildings. National Solar Demonstration Program

    Energy Technology Data Exchange (ETDEWEB)

    None

    1976-04-01

    The general requirements and methods for instrumenting, testing, and evaluating solar HVAC systems forming a part of ERDA's ''Commercial Demonstration Program'' commensurate with ERDA 23A and the Proposed Management Plan 75SDS4270 are defined. Design requirements are specified for the performance of components and subsystems comprising the instrumentation and data gathering system, as well as the support functions required to perform the diagnostic measurements, collection and processing of data, and documentation of reports on solar HVAC system performance, including economic and societal evaluations.

  19. Identification of Barriers Towards Change and Proposal to Institutionalize Continuous Improvement Programs in Manufacturing Operations

    Directory of Open Access Journals (Sweden)

    Alvair Silveira Torres Jr.

    2011-06-01

    Full Text Available A multi case research unfolded into a study in a sample of Brazilian manufacturing companies concerning their Continuous Improvement (CI program in manufacturing operations. Stakeholders interviews and performance analyses were conducted. The study aims to analyze the existence or absence of the institutionalization of a CI culture in manufacturing operations, identify barriers and difficulties within the process and propose a model for change. As a result of the research, it was observed that despite the considerable motivation of staff, rapid gains of the company and superior results during the early phases of the CI program, time and again such results were either not upheld or faded out over time, delivering no significant mid-term or long term results, due to poor management of changes. This happened mainly as a result of lack of strategic alignment at all levels of the organization, translated in measureable activities and projects, coached and mentored by the middle and upper management throughout the implementation and maintenance of the program. The selected cases showed a declining in performance after two years of CI program start up. Learning, union and process ownership among participants by means of interactions, are necessary to absorb and incorporate changes, instead of merely "smart words" .

  20. Views of surgery program directors on the current ACGME and proposed IOM duty-hour standards.

    Science.gov (United States)

    Willis, Ross E; Coverdill, James E; Mellinger, John D; Collins, J Craig; Potts, John R; Dent, Daniel L

    2009-01-01

    The purpose of this study was to survey the experiences of surgery program directors with the current Accreditation Council for Graduate Medical Education (ACGME) duty-hour standards and views of the Institute of Medicine (IOM) proposed duty-hour recommendations. A total of 118 program directors (47.6% of all surgery programs in the US) responded to the survey. Results showed that the current duty-hour standards have hindered clinical education opportunities by reducing or eliminating rotations on many services, didactic teaching conferences, and clinical bedside teaching opportunities. Additionally, patient safety has been compromised by frequent hand offs of care. Most IOM recommendations were perceived as extremely difficult or impossible to implement, with the exception of the moonlighting recommendation. The results indicated that adopting the IOM recommendations is not feasible given current workforce limitations, and most program directors supported maintaining the current duty-hour standards until such time as there is evidence-based outcomes research to direct change. The conclusion was that the current ACGME duty-hour standards have reduced teaching opportunities and narrowed the scope of training.

  1. A proposal for an international program to develop dry recycle of spent nuclear fuel

    International Nuclear Information System (INIS)

    Feinroth, H.

    1999-01-01

    The dry oxidation-reduction process (called OREOX for Oxidation Reduction of Oxide Fuel) being developed by Korea and Canada, in cooperation with IAEA and the US State Department, is limited to recycle of spent LWR fuel into CANDU reactors (DUPIC). When first conceived and demonstrated via irradiation of test elements by Atomics International in 1965, (the process was called AIROX at that time) a wider range of applications was intended, including recycle of spent LWR fuel into LWRs. Studies sponsored by DOE's Idaho Office in 1992 confirmed the applicability of this technology to regions containing LWR's only, and described the potential advantages of such recycle from an environmental, waste management and economic point of view, as compared to the direct disposal option. Recent analyses conducted by the author indicates that such dry recycle may be one of the few acceptable paths remaining for resolution of the US spent fuel storage dilemma that remains consistent with US non-proliferation policy. It is proposed that a new US program be established to develop AIROX dry recycle for use in the US, and this become part of an international cooperative program, including the current Canadian - Korean program, and possibly including participation of other countries wishing to pursue alternatives to the once through cycle, and wet reprocessing. With shared funding of major project elements, such international cooperation would accelerate the demonstration and commercial deployment of dry recycle technology, as compared to separate and independent programs in each country. (author)

  2. 77 FR 47489 - 30-Day Notice of Proposed Information Collection: Form DS-4213, PEPFAR Program Expenditures; OMB...

    Science.gov (United States)

    2012-08-08

    ... provide key information about program costs under PEPFAR on a global level. Applying expenditure results... monitoring, the PEPFAR Finance and Economics Work Group proposes to add reporting of expenditures by program... from implementing partners in countries with PEPFAR programs using a standard tool (DS-4213) via an...

  3. Proposed Social Spending Innovation Research (SSIR) Program: Harnessing American Entrepreneurial Talent to Solve Major U.S. Social Problems

    Science.gov (United States)

    Coalition for Evidence-Based Policy, 2015

    2015-01-01

    The Social Spending Innovation Research (SSIR) proposal seeks to replicate, in social spending, the great success of the Small Business Innovation Research (SBIR) program in technology development. The SBIR program funds technology development by entrepreneurial small companies. The program has spawned breakthrough technologies in diverse areas…

  4. 77 FR 69550 - Proposed Information Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program...

    Science.gov (United States)

    2012-11-19

    ... (Patient Satisfaction Survey Michael E. DeBakey Home Care Program) Activity: Comment Request AGENCY.... DeBakey Home Care Program. DATES: Written comments and recommendations on the proposed collection of...: Patient Satisfaction Survey Michael E. DeBakey Home Care Program, VA Form 10-0476. OMB Control Number...

  5. 75 FR 77607 - Privacy Act of 1974; Proposed New System of Records; Veterinary Medicine Loan Repayment Program

    Science.gov (United States)

    2010-12-13

    ...; Proposed New System of Records; Veterinary Medicine Loan Repayment Program AGENCY: National Institute of..., ``Veterinary Medicine Loan Repayment Program Records System, USDA/NIFA-1.'' This newly established system will... Sherman; National Program Leader, Veterinary Science; National Institute of Food and Agriculture...

  6. 75 FR 1408 - Pick-Sloan Missouri Basin Program, Eastern and Western Division Proposed Project Use Power Rate

    Science.gov (United States)

    2010-01-11

    ... of Proposed Pick-Sloan Missouri Basin Program, Eastern and Western Divisions, Project Use Power Rate...) for Project Use Power for the Pick-Sloan Missouri Basin Program (P-SMBP), Eastern and Western... DEPARTMENT OF THE INTERIOR Bureau of Reclamation Pick-Sloan Missouri Basin Program, Eastern and...

  7. [The Articulator of Primary Health Care Program: an innovative proposal for qualification of Primary Health Care].

    Science.gov (United States)

    Doricci, Giovanna Cabral; Guanaes-Lorenzi, Carla; Pereira, Maria José Bistafa

    2017-06-01

    In 2009, the Secretary of State for Health of Sao Paulo created a Program with a view to qualify the primary care in the state. This proposal includes a new job function, namely the articulator of primary care. Due to the scarcity of information about the practice of these new professionals in the scientific literature, this article seeks to analyze how articulators interpret their function and how they describe their daily routines. Thirteen articulators were interviewed. The interviews were duly analyzed by qualitative delineation. The results describe three themes: 1)Roles of the articulator: technical communicator and political advisor; 2) Activities performed to comply with the expected roles, examples being diagnosis of the municipalities, negotiation of proposals, participation in meetings, visits to municipalities; and 3) Challenges of the role, which are configured as challenges to the health reform process, examples being the lack of physical and human resources, activities of professionals in the medical-centered model, among others. The conclusion drawn is that the Program has great potential to provide input for the development and enhancement of Primary Care. Nevertheless, there are a series of challenges to be overcome, namely challenges to the context per se.

  8. Proposal of a Methodology of Stakeholder Analysis for the Brazilian Satellite Space Program

    Directory of Open Access Journals (Sweden)

    Mônica Elizabeth Rocha de Oliveira

    2012-03-01

    Full Text Available To ensure the continuity and growth of space activities in Brazil, it is fundamental to persuade the Brazilian society and its representatives in Government about the importance of investments in space activities. Also, it is important to convince talented professionals to place space activities as an object of their interest; the best schools should also be convinced to offer courses related to the space sector; finally, innovative companies should be convinced to take part in space sector activities, looking to returns, mainly in terms of market differentiation and qualification, as a path to take part in high-technology and high-complexity projects. On the one hand, this process of convincing or, more importantly, committing these actors to space activities, implies a thorough understanding of their expectations and needs, in order to plan how the system/organization can meet them. On the other hand, if stakeholders understand how much they can benefit from this relationship, their consequent commitment will very much strengthen the action of the system/organization. With this framework in perspective, this paper proposes a methodology of stakeholder analysis for the Brazilian satellite space program. In the exercise developed in the article, stakeholders have been identified from a study of the legal framework of the Brazilian space program. Subsequently, the proposed methodology has been applied to the planning of actions by a public organization.

  9. Seminar program for postgraduate specialty training in general practice: proposal for a 5-year thematic catalogue

    Directory of Open Access Journals (Sweden)

    Sommer, Susanne

    2017-11-01

    Full Text Available Introduction: In different German regions, seminar programs have been conducted for General practice residents. In each region, selection and teaching of learning content is conducted in a different manner. So far, no structured, standardized curriculum has been implemented nationwide. We have investigated, if the development of a common 5-year program of learning topics is conceivable between the different university departments of General practice in Germany.Method: The seminar program working group of the DEGAM (German College of General Practitioners and Family Physicians has conducted an online survey based on information gathered via preliminary telephone conference (n=7; physicians with postgraduate teaching experience among all German university departments of General Practice and two non-university teaching institutions, identified via the internet. 884 topics were extracted from 14 Seminar programs. The topics were entered in a database, discussed and categorized: Practice management/practice work flow/standardized documentation forms/quality management (n=33 topics, common acute and chronic diseases, including disease management programs (n=29 topics, communication, neurological, psychological and psychiatric consultations (n=24 topics, common medical problems, including eye, ear, nose, throat, skin and pediatric problems (n=99 Topics family physicians general approach, including epidemiology, shared decision making, test of time (n=42 Topics. These topics have been rated for priority and desirable number of teaching-units.Results: A catalogue of 111 topics was designed, encompassing 160 teaching units. There is a suggestion of wide topics collections plus an add-on catalogue.Conclusion: A proposal for a 5-year-thematic catalogue for postgraduate training of general practice residents in Germany has been developed. This newly developed curriculum has the potential to improve knowledge and skills that have not been covered during in

  10. Optimisation of ATP determination in drinking water

    DEFF Research Database (Denmark)

    Corfitzen, Charlotte B.; Albrechtsen, Hans-Jørgen

    Adenosine Triphosphate (ATP) can be used as a relative measure of cell activity, and is measured by the light output from the reaction between luciferin and ATP catalyzed by firefly luciferase. The measurement has potential as a monitoring and surveillance tool within drinking water distribution,...... be separated from the water phase by filtration.......Adenosine Triphosphate (ATP) can be used as a relative measure of cell activity, and is measured by the light output from the reaction between luciferin and ATP catalyzed by firefly luciferase. The measurement has potential as a monitoring and surveillance tool within drinking water distribution...... and an Advance Coupe luminometer. The investigations showed a 60 times higher response of the PCP-kit, making it more suitable for measurement of samples with low ATP content. ATP-standard dilutions prepared in tap water were stable for at least 15 months when stored frozen at -80ºC, and storage of large...

  11. THE PROPOSED MODEL OF COLLABORATIVE VIRTUAL LEARNING ENVIRONMENT FOR INTRODUCTORY PROGRAMMING COURSE

    Directory of Open Access Journals (Sweden)

    Mahfudzah OTHMAN

    2012-01-01

    Full Text Available This paper discusses the proposed model of the collaborative virtual learning system for the introductory computer programming course which uses one of the collaborative learning techniques known as the “Think-Pair-Share”. The main objective of this study is to design a model for an online learning system that facilitates the collaborative learning activities in a virtual environment such as online communications and pair or small group discussions. In order to model the virtual learning environment, the RUP methodology has been used where it involves the data collection phase and the analysis and design phase. Fifty respondents have been randomly selected to participate in the data collection phase to investigate the students’ interest and learning styles as well as their learning preferences. The results have shown the needs for the development of online small group discussions that can be used as an alternative learning style for programming courses. The proposed design of the virtual learning system named as the Online Collaborative Learning System or OCLS is being depicted using the object-oriented models which are the use-case model and class diagram in order to show the concise processes of virtual “Think-Pair-Share” collaborative activities. The “Think-Pair-Share” collaborative learning technique that is being used in this model has been chosen because of its simplicity and relatively low-risk. This paper also presents the proposed model of the system’s architecture that will become the guidelines for the physical development of OCLS using the web-based applications.

  12. [The Purpose of Medical Education: Proposal to Standardize a System of Credits for Medical Specializations Programs].

    Science.gov (United States)

    Cañar, Carlos Andrés Pineda

    2012-01-01

    This article analyzes the concept of an academic credit system and proposes a way to systematize medical specialization programs. The credit system is a way to recognize and standardize the total time that a student must devote to their training. Thus, a credit equal to a certain number of hours of classroom training and independent activities is proposed. An educational program is expressed in the number of credits needed for the whole training process to achieve the competencies expected. A review of the concept of competition in education is also performed. The introduction of the term and its relation to the need to measure performance in future professionals according to labor market needs is identified. A critical discussion about skills defining the different types of skills in the educational field is later discussed. Subsequently, the Colombian regulatory framework is presented concerning the powers, in particular, Decree 1295 of 2010, which defines one academic credit equal to 48 hours in a semester, of which 16 hours are classroom and 32 hours are independent study. A tor of the major milestones in the history of medical education is later made. The structure of credits and contact hours, independent of postgraduate psychiatry in the country is reviewed showing the heterogeneity in their approach. The proposal is presented, defining the types of classroom activities and how to calculate the hours of independent study by type of classroom activity. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  13. Cellular function and pathological role of ATP13A2 and related P-type transport ATPases in Parkinson's disease and other neurological disorders

    DEFF Research Database (Denmark)

    van Veen, Sarah; Sørensen, Danny M.; Holemans, Tine

    2014-01-01

    -type ATPases. We critically review the available data concerning the role of ATP13A2 in heavy metal transport and propose a possible alternative hypothesis that ATP13A2 might be a flippase. As a flippase, ATP13A2 may transport an organic molecule, such as a lipid or a peptide, from one membrane leaflet...

  14. Mechanisms of constitutive and ATP-evoked ATP release in neonatal mouse olfactory epithelium

    Directory of Open Access Journals (Sweden)

    Hayoz Sébastien

    2012-05-01

    Full Text Available Abstract Background ATP is an extracellular signaling molecule with many ascribed functions in sensory systems, including the olfactory epithelium. The mechanism(s by which ATP is released in the olfactory epithelium has not been investigated. Quantitative luciferin-luciferase assays were used to monitor ATP release, and confocal imaging of the fluorescent ATP marker quinacrine was used to monitor ATP release via exocytosis in Swiss Webster mouse neonatal olfactory epithelial slices. Results Under control conditions, constitutive release of ATP occurs via exocytosis, hemichannels and ABC transporters and is inhibited by vesicular fusion inhibitor Clostridium difficile toxin A and hemichannel and ABC transporter inhibitor probenecid. Constitutive ATP release is negatively regulated by the ATP breakdown product ADP through activation of P2Y receptors, likely via the cAMP/PKA pathway. In vivo studies indicate that constitutive ATP may play a role in neuronal homeostasis as inhibition of exocytosis inhibited normal proliferation in the OE. ATP-evoked ATP release is also present in mouse neonatal OE, triggered by several ionotropic P2X purinergic receptor agonists (ATP, αβMeATP and Bz-ATP and a G protein-coupled P2Y receptor agonist (UTP. Calcium imaging of P2X2-transfected HEK293 “biosensor” cells confirmed the presence of evoked ATP release. Following purinergic receptor stimulation, ATP is released via calcium-dependent exocytosis, activated P2X1,7 receptors, activated P2X7 receptors that form a complex with pannexin channels, or ABC transporters. The ATP-evoked ATP release is inhibited by the purinergic receptor inhibitor PPADS, Clostridium difficile toxin A and two inhibitors of pannexin channels: probenecid and carbenoxolone. Conclusions The constitutive release of ATP might be involved in normal cell turn-over or modulation of odorant sensitivity in physiological conditions. Given the growth-promoting effects of ATP, ATP-evoked ATP

  15. Conformational dynamics of ATP/Mg:ATP in motor proteins via data mining and molecular simulation

    Science.gov (United States)

    Bojovschi, A.; Liu, Ming S.; Sadus, Richard J.

    2012-08-01

    The conformational diversity of ATP/Mg:ATP in motor proteins was investigated using molecular dynamics and data mining. Adenosine triphosphate (ATP) conformations were found to be constrained mostly by inter cavity motifs in the motor proteins. It is demonstrated that ATP favors extended conformations in the tight pockets of motor proteins such as F1-ATPase and actin whereas compact structures are favored in motor proteins such as RNA polymerase and DNA helicase. The incorporation of Mg2+ leads to increased flexibility of ATP molecules. The differences in the conformational dynamics of ATP/Mg:ATP in various motor proteins was quantified by the radius of gyration. The relationship between the simulation results and those obtained by data mining of motor proteins available in the protein data bank is analyzed. The data mining analysis of motor proteins supports the conformational diversity of the phosphate group of ATP obtained computationally.

  16. Single K ATP channel opening in response to action potential firing in mouse dentate granule neurons.

    Science.gov (United States)

    Tanner, Geoffrey R; Lutas, Andrew; Martínez-François, Juan Ramón; Yellen, Gary

    2011-06-08

    ATP-sensitive potassium channels (K(ATP) channels) are important sensors of cellular metabolic state that link metabolism and excitability in neuroendocrine cells, but their role in nonglucosensing central neurons is less well understood. To examine a possible role for K(ATP) channels in modulating excitability in hippocampal circuits, we recorded the activity of single K(ATP) channels in cell-attached patches of granule cells in the mouse dentate gyrus during bursts of action potentials generated by antidromic stimulation of the mossy fibers. Ensemble averages of the open probability (p(open)) of single K(ATP) channels over repeated trials of stimulated spike activity showed a transient increase in p(open) in response to action potential firing. Channel currents were identified as K(ATP) channels through blockade with glibenclamide and by comparison with recordings from Kir6.2 knock-out mice. The transient elevation in K(ATP) p(open) may arise from submembrane ATP depletion by the Na(+)-K(+) ATPase, as the pump blocker strophanthidin reduced the magnitude of the elevation. Both the steady-state and stimulus-elevated p(open) of the recorded channels were higher in the presence of the ketone body R-β-hydroxybutyrate, consistent with earlier findings that ketone bodies can affect K(ATP) activity. Using perforated-patch recording, we also found that K(ATP) channels contribute to the slow afterhyperpolarization following an evoked burst of action potentials. We propose that activity-dependent opening of K(ATP) channels may help granule cells act as a seizure gate in the hippocampus and that ketone-body-mediated augmentation of the activity-dependent opening could in part explain the effect of the ketogenic diet in reducing epileptic seizures.

  17. 76 FR 3080 - Agency Information Collection Activities: Proposed Collection; Comment Request-Food Programs...

    Science.gov (United States)

    2011-01-19

    ... (SNAP), the National School Lunch Program (NSLP), the School Breakfast Program (SBP), Special... program funds that cover all benefit costs, and a significant portion of administrative expenses. Under...

  18. Genetic variation in ATP5O is associated with skeletal muscle ATP50 mRNA expression and glucose uptake in young twins.

    Directory of Open Access Journals (Sweden)

    Tina Rönn

    Full Text Available BACKGROUND: Impaired oxidative capacity of skeletal muscle mitochondria contribute to insulin resistance and type 2 diabetes (T2D. Furthermore, mRNA expression of genes involved in oxidative phosphorylation, including ATP5O, is reduced in skeletal muscle from T2D patients. Our aims were to investigate mechanisms regulating ATP5O expression in skeletal muscle and association with glucose metabolism, and the relationship between ATP5O single nucleotide polymorphisms (SNPs and risk of T2D. METHODOLOGY/PRINCIPAL FINDINGS: ATP5O mRNA expression was analyzed in skeletal muscle from young (n = 86 and elderly (n = 68 non-diabetic twins before and after a hyperinsulinemic euglycemic clamp. 11 SNPs from the ATP5O locus were genotyped in the twins and a T2D case-control cohort (n = 1466. DNA methylation of the ATP5O promoter was analyzed in twins (n = 22 using bisulfite sequencing. The mRNA level of ATP5O in skeletal muscle was reduced in elderly compared with young twins, both during basal and insulin-stimulated conditions (p<0.0005. The degree of DNA methylation around the transcription start of ATP5O was <1% in both young and elderly twins and not associated with mRNA expression (p = 0.32. The mRNA level of ATP5O in skeletal muscle was positively related to insulin-stimulated glucose uptake (regression coefficient = 6.6; p = 0.02. Furthermore, two SNPs were associated with both ATP5O mRNA expression (rs12482697: T/T versus T/G; p = 0.02 and rs11088262: A/A versus A/G; p = 0.004 and glucose uptake (rs11088262: A/A versus A/G; p = 0.002 and rs12482697: T/T versus T/G; p = 0.005 in the young twins. However, we could not detect any genetic association with T2D. CONCLUSIONS/SIGNIFICANCE: Genetic variation and age are associated with skeletal muscle ATP5O mRNA expression and glucose disposal rate, suggesting that combinations of genetic and non-genetic factors may cause the reduced expression of ATP5O in T2D muscle. These findings propose a role for ATP5O, in

  19. A program in medium energy nuclear physics. Progress report and continuation proposal October 1, 1995

    International Nuclear Information System (INIS)

    Berman, B.L.; Dhuga, K.S.

    1995-01-01

    This progress report and continuation proposal summarizes our achievements for the period from July 1, 1994 to September 30, 1995 and requests continued funding for our program in experimental medium-energy nuclear physics. The focus of our program remains the understanding of the short-range part of the strong interaction in the nuclear medium. In the past year we have focused our attention ever more sharply on experiments with real tagged photons, and we have successfully defended two new experimental proposals: Photofission of Actinide and Preactinide Nuclei at SAL and Photoproduction of the ρ Meson from the Proton with Linearly Polarized Photons at CEBAF. (We are co-spokespersons on two previously approved Hall-B experiments at CEBAF, Photoreactions on 3 He and Photoabsorption and Photofission of Nuclei.) As part of the team that is instrumenting the Photon Tagger for Hall B; we report excellent progress on the focal-plane detector array that is being built at our Nuclear Detector Laboratory, as well as progress on our plans for instrumentation of a tagged polarized-photon beam using coherent bremsstrahlung. Also, we shall soon receive a large computer system (from the SSC) which will form the basis for our new Data Analysis Center, which, like the Nuclear Detector Laboratory, will be operated under the auspices of The George Washington University Center for Nuclear Studies. Finally, during the past year we have published six more papers on the results of our measurements of pion scattering at LAMPF and of electron scattering at NIKHEF and Bates, and we can report that nearly all of the remaining papers documenting this long series of measurements are in the pipeline

  20. 78 FR 70958 - 30-Day Notice of Proposed Information Collection: Recordkeeping for HUD's Continuum of Care Program

    Science.gov (United States)

    2013-11-27

    ... individuals, families, and communities by homelessness; promote access to and effective utilization of... Information Collection: Recordkeeping for HUD's Continuum of Care Program AGENCY: Office of the Chief Information Officer, HUD. ACTION: Notice. SUMMARY: HUD has submitted the proposed information collection...

  1. Plasma ATP concentration and venous oxygen content in the forearm during dynamic handgrip exercise

    Directory of Open Access Journals (Sweden)

    Askew Christopher D

    2009-12-01

    Full Text Available Abstract Background It has been proposed that adenosine triphosphate (ATP released from red blood cells (RBCs may contribute to the tight coupling between blood flow and oxygen demand in contracting skeletal muscle. To determine whether ATP may contribute to the vasodilatory response to exercise in the forearm, we measured arterialised and venous plasma ATP concentration and venous oxygen content in 10 healthy young males at rest, and at 30 and 180 seconds during dynamic handgrip exercise at 45% of maximum voluntary contraction (MVC. Results Venous plasma ATP concentration was elevated above rest after 30 seconds of exercise (P Conclusions Collectively these results indicate that ATP in the plasma originated from the muscle microcirculation, and are consistent with the notion that deoxygenation of the blood perfusing the muscle acts as a stimulus for ATP release. That ATP concentration was elevated just 30 seconds after the onset of exercise also suggests that ATP may be a contributing factor to the blood flow response in the transition from rest to steady state exercise.

  2. A program in medium-energy nuclear physics. Renewal proposal and progress report August 1, 1994

    International Nuclear Information System (INIS)

    Berman, B.L.; Dhuga, K.S.

    1994-01-01

    This renewal proposal requests continued funding for our program in experimental medium-energy nuclear physics. The focus of our program remains the understanding of the short-range part of the strong interaction in the nuclear medium. In the past three years we have focused our attention ever more sharply on experiments with real tagged photons at CEBAF. We are part of the Hall-B Collaboration at CEBAF. We are co-spokespersons on two approved CEBAF experiments, Photoreactions on 3 He and Photoabsorption and Photofission of Nuclei, and we are preparing another, Nondiffractive Photoproduction of the ρ Meson with Linearly Polarized Photons, for presentation to the next CEBAF PAC. We are part of the team that is instrumenting the Photon Tagger and a high-energy tagged polarized-photon beam for Hall B; some of the instrumentation for these projects is being built at our Nuclear Detector Laboratory, under the auspices of The George Washington University Center for Nuclear Studies. Our recent measurements of pion scattering from 3 H and 3 He at LAMPF and of cluster knockout from few-body nuclei at NIKHEF have yielded very provocative results, showing the importance of the very light nuclei as a laboratory for quantifying important aspects of the nuclear many-body force. We look forward to expanding our studies of short-range forces in nuclei, particularly the very fight nuclei using electromagnetic probes and employing the extraordinary power of CEBAF and the CLAS

  3. Proposed performance standards for the Agricultural Hazardous Occupations Order certification training program.

    Science.gov (United States)

    French, B F; Field, W E; Tormoehlen, R

    2007-07-01

    The performance standards that accompany Gearing Up for Safety, the agricultural production safety training curriculum for youth, were designed to meet the certification testing requirements of the Agricultural Hazardous Occupations Order (AgHOs) certification training program. The AgHOs requires that certain youth who are older than 13 and younger than 16 years of age complete a prescribed training program before being eligible for employment on farms to perform certain tasks considered hazardous. These training resources will be available for implementation and can be accessed by contacting the second author. To our knowledge, up until this time, few, if any, standardized testing procedures or instruments have had the necessary psychometric evidence to support use of the resulting scores to assess the readiness of youth to meet the basic certification requirements contained in the AgHOs. This article describes the rationale, methods, and key findings from a standard-setting session held to establish minimum passing scores for a proposed testing process. The test will be used as a component of the Gearing Up for Safety certification process for youth workers seeking employment to perform job functions as specified under the AgHOs. Readers may be able to apply this standardized testing process, or similarly accepted processes, to other or future testing and certification projects involving agricultural safety and health.

  4. Proposals to enhance thermal efficiency programs and air pollution control in south-central Chile

    International Nuclear Information System (INIS)

    Schueftan, Alejandra; González, Alejandro D.

    2015-01-01

    Major cities in South-central Chile suffer high levels of particulate matter PM 10 and PM 2.5 due to combustion of solid fuels for heating. Exposure to these air pollutants is recognized as a major contribution to ill health in the region. Here we discuss new strategies to reduce air pollution. Regulations and subsidies focusing on improved combustion by providing drier wood fuel and better stoves have been in effect since 2007. However, air pollution due to combustion of wood fuel has been steadily rising, along with reports on health consequences. The paper analyzes a survey of 2025 households in the city of Valdivia, which found that wood fuel quality, stove renewal, and awareness of programs are strongly affected by income level, and that higher consumption of wood fuel is found in households already having better stoves and drier wood fuel. The analysis suggests that regulations intended to improve combustion are influenced by user's behavior and have limited potential for lowering pollution. We conclude that thermal refurbishment has a larger potential for improvement, not yet been implemented as an energy policy for the majority. Here we propose improvements and additions to current programs to enhance effectiveness and cover the whole social spectrum. - Highlights: • High levels of PM 2.5 from wood combustion affect cities of south-central Chile. • Current programs on dry wood fuel and stoves renewal have not reduced air pollution. • Real operation of wood stoves strongly depends on user's behavior. • Buildings' energy efficiency has greater potential for reducing emissions. • Retrofit prevents degradation of native forest and improves indoor temperature

  5. Muscle interstitial ATP and norepinephrine concentrations in the human leg during exercise and ATP infusion

    DEFF Research Database (Denmark)

    Mortensen, Stefan P.; Gonzalez-Alonso, Jose; Nielsen, Jens Jung

    2009-01-01

    ATP and NE concentrations to gain insight into the interstitial and intravascular mechanisms by which ATP causes muscle vasodilation and sympatholysis. Leg hemodynamics and muscle interstitial nucleotide and norepinephrine (NE) concentrations were measured during: 1) femoral arterial ATP infusion (0......, respectively (Pcontracting muscle (Pmuscle, whereas interstitial NE concentrations increased similarly in both active...... and inactive muscles. These results suggest that the vasodilatory and sympatholytic effects of intraluminal ATP are mainly mediated via endothelial prinergic receptors. Intraluminal ATP and muscle contractions appear to modulate sympathetic nerve activity by inhibiting the effect of NE rather than blunting its...

  6. 76 FR 70156 - Proposed 5-Year Outer Continental Shelf (OCS) Oil and Gas Leasing Program for 2012-2017

    Science.gov (United States)

    2011-11-10

    ... Analysis for the OCS 5-Year Program 2012-2017: Theory and Methodology (BOEM 050-2011), a paper containing a..., which remain the two areas of highest resource potential and interest, the Proposed Program schedules..., and setting the fiscal terms and conditions by individual lease sale, based on a current assessment of...

  7. Mutations in the Atp1p and Atp3p subunits of yeast ATP synthase differentially affect respiration and fermentation in Saccharomyces cerevisiae.

    Science.gov (United States)

    Francis, Brian R; White, Karen H; Thorsness, Peter E

    2007-04-01

    ATP1-111, a suppressor of the slow-growth phenotype of yme1Delta lacking mitochondrial DNA is due to the substitution of phenylalanine for valine at position 111 of the alpha-subunit of mitochondrial ATP synthase (Atp1p in yeast). The suppressing activity of ATP1-111 requires intact beta (Atp2p) and gamma (Atp3p) subunits of mitochondrial ATP synthase, but not the stator stalk subunits b (Atp4p) and OSCP (Atp5p). ATP1-111 and other similarly suppressing mutations in ATP1 and ATP3 increase the growth rate of wild-type strains lacking mitochondrial DNA. These suppressing mutations decrease the growth rate of yeast containing an intact mitochondrial chromosome on media requiring oxidative phosphorylation, but not when grown on fermentable media. Measurement of chronological aging of yeast in culture reveals that ATP1 and ATP3 suppressor alleles in strains that contain mitochondrial DNA are longer lived than the isogenic wild-type strain. In contrast, the chronological life span of yeast cells lacking mitochondrial DNA and containing these mutations is shorter than that of the isogenic wild-type strain. Spore viability of strains bearing ATP1-111 is reduced compared to wild type, although ATP1-111 enhances the survival of spores that lacked mitochondrial DNA.

  8. 76 FR 3609 - Proposed Information Collection; Comment Request; Census in Schools and Partnership Program Research

    Science.gov (United States)

    2011-01-20

    ... in Schools and Partnership Program Research AGENCY: U.S. Census Bureau, Commerce. ACTION: Notice... Schools (CIS) Program and the Partnership Program (PP) with three primary objectives: (1) To increase the.... The CIS Program educated primary and secondary school students about the 2010 Census; the students, in...

  9. Metal-dependent regulation of ATP7A and ATP7B in fibroblast cultures

    Directory of Open Access Journals (Sweden)

    Lenartowicz Malgorzata

    2016-08-01

    Full Text Available Deficiency of one of the copper transporters ATP7A and ATP7B leads to the rare X-linked disorder Menkes Disease (MD or the rare autosomal disorder Wilson disease (WD, respectively. In order to investigate whether the ATP7A and the ATP7B genes may be transcriptionally regulated, we measured the expression level of the two genes at various concentrations of iron, copper and insulin. Treating fibroblasts from controls or from individuals with MD or WD for 3 and10 days with iron chelators revealed that iron deficiency led to increased transcript levels of both ATP7A and ATP7B. Copper deficiency obtained by treatment with the copper chelator led to a downregulation of ATP7A in the control fibroblasts, but surprisingly not in the WD fibroblasts. In contrast, the addition of copper led to an increased expression of ATP7A, but a decreased expression of ATP7B. Thus, whereas similar regulation patterns for the two genes were observed in response to iron deficiency, different responses were observed after changes in the access to copper. Mosaic fibroblast cultures from female carriers of MD treated with copper or copper chelator for 6-8 weeks led to clonal selection. Cells that express the normal ATP7A allele had a selective growth advantage at high copper concentrations, whereas more surprisingly, cells that express the mutant ATP7A allele had a selective growth advantage at low copper concentrations. Thus, although the transcription of ATP7A is regulated by copper, clonal growth selection in mosaic cell cultures is affected by the level of copper. Female carriers of MD are rarely affected probably due to a skewed inactivation of the X-chromosome bearing the ATP7A mutation.

  10. Review of current Southern California edison load management programs and proposal for a new market-driven, mass-market, demand-response program

    Energy Technology Data Exchange (ETDEWEB)

    Weller, G.H.

    2002-01-01

    Utility load management programs, including direct load control and interruptible load programs, constitute a large installed base of controllable loads that are employed by utilities as system reliability resources. In response to energy supply shortfalls expected during the summer of 2001, the California Public Utilities Commission in spring 2001 authorized new utility load management programs as well as revisions to existing programs. This report provides an independent review of the designs of these new programs for a large utility (Southern California Edison) and suggests possible improvements to enhance the price responsiveness of the customer actions influenced by these programs. The report also proposes a new program to elicit a mass-market demand response to utility price signals.

  11. Redox regulation of ATP sulfurylase in microalgae

    Czech Academy of Sciences Publication Activity Database

    Prioretti, L.; Lebrun, R.; Gontero, B.; Giordano, Mario

    2016-01-01

    Roč. 478, č. 4 (2016), s. 1555-1562 ISSN 0006-291X Institutional support: RVO:61388971 Keywords : ATP sulfurylase * cysteine * Sulfur metabolism Subject RIV: EE - Microbiology, Virology Impact factor: 2.466, year: 2016

  12. The Role of ATP in Sleep Regulation

    Directory of Open Access Journals (Sweden)

    Sachiko eChikahisa

    2011-12-01

    Full Text Available One of the functions of sleep is to maintain energy balance in the brain. There are a variety of hypotheses related to how metabolic pathways interact with sleep/wake regulation. A major finding that demonstrates an interaction between sleep and metabolic homeostasis is the involvement of adenosine in sleep homeostasis. An accumulation of adenosine is supplied from ATP, which can act as an energy currency in the cell. Extracellularly, ATP can act as an activity-dependent signaling molecule, especially in regard to communication between neurons and glia, including astrocytes. Furthermore, the intracellular AMP/ATP ratio controls the activity of AMP-activated protein kinase (AMPK, which is a potent energy regulator and is recently reported to play a role in the regulation of sleep homeostasis. Brain ATP may support multiple functions in the regulation of the sleep/wake cycle and sleep homeostasis.

  13. Refining Risk Adjustment for the Proposed CMS Surgical Hip and Femur Fracture Treatment Bundled Payment Program.

    Science.gov (United States)

    Cairns, Mark A; Ostrum, Robert F; Clement, R Carter

    2018-02-21

    The U.S. Centers for Medicare & Medicaid Services (CMS) has been considering the implementation of a mandatory bundled payment program, the Surgical Hip and Femur Fracture Treatment (SHFFT) model. However, bundled payments without appropriate risk adjustment may be inequitable to providers and may restrict access to care for certain patients. The SHFFT proposal includes adjustment using the Diagnosis-Related Group (DRG) and geographic location. The goal of the current study was to identify and quantify patient factors that could improve risk adjustment for SHFFT bundled payments. We retrospectively reviewed a 5% random sample of Medicare data from 2008 to 2012. A total of 27,898 patients were identified who met SHFFT inclusion criteria (DRG 480, 481, and 482). Reimbursement was determined for each patient over the bundle period (the surgical hospitalization and 90 days of post-discharge care). Multivariable regression was performed to test demographic factors, comorbidities, geographic location, and specific surgical procedures for associations with reimbursement. The average reimbursement was $23,632 ± $17,587. On average, reimbursements for male patients were $1,213 higher than for female patients (p payments; e.g., reimbursement for those ≥85 years of age averaged $2,282 ± $389 less than for those aged 65 to 69 (p reimbursement, but dementia was associated with lower payments, by an average of $2,354 ± $243 (p reimbursement ranging from $22,527 to $24,033. Less common procedures varied by >$20,000 in average reimbursement (p reimbursement (p reimbursed by an average of $10,421 ± $543 more than DRG 482. Payments varied significantly by state (p ≤ 0.01). Risk adjustment incorporating specific comorbidities demonstrated better performance than with use of DRG alone (r = 0.22 versus 0.15). Our results suggest that the proposed SHFFT bundled payment model should use more robust risk-adjustment methods to ensure that providers are reimbursed fairly and that

  14. Minority Engineering Program Pipeline: A Proposal to Increase Minority Student Enrollment and Retention in Engineering

    Science.gov (United States)

    Charity, Pamela C.; Klein, Paul B.; Wadhwa, Bhushan

    1995-01-01

    The Cleveland State University Minority Engineering Program Pipeline consist of programs which foster engineering career awareness, academic enrichment, and professional development for historically underrepresented minority studies. The programs involved are the Access to Careers in Engineering (ACE) Program for high school pre-engineering students: the LINK Program for undergraduate students pursuing degree which include engineering; and the PEP (Pre-calculus Enrichment Program) and EPIC (Enrichment Program in Calculus) mathematics programs for undergraduate academic enrichment. The pipeline is such that high school graduates from the ACE Program who enroll at Cleveland State University in pursuit of engineering degrees are admitted to the LINK Program for undergraduate level support. LINK Program students are among the minority participants who receive mathematics enrichment through the PEP and EPIC Programs for successful completion of their engineering required math courses. THese programs are interdependent and share the goal of preparing minority students for engineering careers by enabling them to achieve academically and obtain college degree and career related experience.

  15. 76 FR 7546 - Proposed Information Collection; Comment Request; Prohibited Species Donation (PSD) Program

    Science.gov (United States)

    2011-02-10

    ... Collection; Comment Request; Prohibited Species Donation (PSD) Program AGENCY: National Oceanic and... species donation (PSD) program for Pacific salmon and Pacific halibut has effectively reduced regulatory... individuals through tax-exempt organizations. Vessels and processing plants participating in the donation...

  16. 78 FR 7437 - Proposed Collection; Comment Request (60-Day FRN); The Clinical Trials Reporting Program (CTRP...

    Science.gov (United States)

    2013-02-01

    ... for public comment on proposed data collection projects, the National Institutes of Health (NIH) will publish periodic summaries of proposed projects to be submitted to the Office of Management and Budget... proposed collection of information, including the validity of the methodology and assumptions used; (3) The...

  17. 77 FR 6863 - Proposed Collection; Comment Request for VITA/TCE Program Forms

    Science.gov (United States)

    2012-02-09

    .../TCE Program Forms AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for... VITA/TCE Program Forms 14310, 8653, 8654, and 14024. DATES: Written comments should be received on or... . SUPPLEMENTARY INFORMATION: Title: VITA/TCE Program Forms. OMB Number: 1545-2222. Form Number: Forms 14310, 8653...

  18. 77 FR 39722 - Notice of Proposed Information Collection for Public Comment: Housing Choice Voucher Program...

    Science.gov (United States)

    2012-07-05

    ... overhead costs, transaction counts, and recent changes in voucher program operations (2 staff x 20 hours x... information on the costs of administering the HCV program across a national sample of high- [[Page 39723... via interviews and document review on overhead costs, other costs related to HCV program...

  19. 78 FR 46332 - Proposed Information Collection Request; Comment Request; National Estuary Program

    Science.gov (United States)

    2013-07-31

    ... Request; Comment Request; National Estuary Program AGENCY: Environmental Protection Agency (EPA). ACTION... request (ICR), ``National Estuary Program'' (EPA ICR No. 1500.08, OMB Control No. 2040-0138 to the Office... comments to OMB. Abstract: The National Estuary Program (NEP) involves collecting information from the...

  20. 75 FR 47346 - Proposed Renewal Without Change; Comment Request; Anti-Money Laundering Programs; Special Due...

    Science.gov (United States)

    2010-08-05

    ...; Comment Request; Anti-Money Laundering Programs; Special Due Diligence Programs for Certain Foreign... reasonably designed to detect and report money laundering through correspondent accounts and private banking..., P.O. Box 39, Vienna, VA 22183, Attention: Comments on Anti-Money Laundering Program and Special Due...

  1. 75 FR 21016 - Notice of Proposed Information Collection: Comment Request; The Green Retrofit Program of the...

    Science.gov (United States)

    2010-04-22

    ... Information Collection: Comment Request; The Green Retrofit Program of the American Recovery and... Retrofit Program authorized by the American Recovery and Revitalization Act of 2009. The legislation.... The Green Retrofit Program is detailed in HUD Notice H 09-02 issued on May 13, 2009. This Notice is...

  2. 75 FR 32182 - Medicaid Program: Proposed Implementation of Section 614 of the Children's Health Insurance...

    Science.gov (United States)

    2010-06-07

    ... of the Children's Health Insurance Program Reauthorization Act of 2009 for Adjustments to the Federal... subject to adjustment pursuant to section 614 of the Children's Health Insurance Program Reauthorization... assistance expenditures under the Children's Health Insurance Program under title XXI of the Social Security...

  3. atpE gene as a new useful specific molecular target to quantify Mycobacterium in environmental samples

    Science.gov (United States)

    2013-01-01

    Background The environment is the likely source of many pathogenic mycobacterial species but detection of mycobacteria by bacteriological tools is generally difficult and time-consuming. Consequently, several molecular targets based on the sequences of housekeeping genes, non-functional RNA and structural ribosomal RNAs have been proposed for the detection and identification of mycobacteria in clinical or environmental samples. While certain of these targets were proposed as specific for this genus, most are prone to false positive results in complex environmental samples that include related, but distinct, bacterial genera. Nowadays the increased number of sequenced genomes and the availability of software for genomic comparison provide tools to develop novel, mycobacteria-specific targets, and the associated molecular probes and primers. Consequently, we conducted an in silico search for proteins exclusive to Mycobacterium spp. genomes in order to design sensitive and specific molecular targets. Results Among the 3989 predicted proteins from M. tuberculosis H37Rv, only 11 proteins showed 80% to 100% of similarity with Mycobacterium spp. genomes, and less than 50% of similarity with genomes of closely related Corynebacterium, Nocardia and Rhodococcus genera. Based on DNA sequence alignments, we designed primer pairs and a probe that specifically detect the atpE gene of mycobacteria, as verified by quantitative real-time PCR on a collection of mycobacteria and non-mycobacterial species. The real-time PCR method we developed was successfully used to detect mycobacteria in tap water and lake samples. Conclusions The results indicate that this real-time PCR method targeting the atpE gene can serve for highly specific detection and precise quantification of Mycobacterium spp. in environmental samples. PMID:24299240

  4. Non-bilayer structures in mitochondrial membranes regulate ATP synthase activity.

    Science.gov (United States)

    Gasanov, Sardar E; Kim, Aleksandr A; Yaguzhinsky, Lev S; Dagda, Ruben K

    2018-02-01

    Cardiolipin (CL) is an anionic phospholipid at the inner mitochondrial membrane (IMM) that facilitates the formation of transient non-bilayer (non-lamellar) structures to maintain mitochondrial integrity. CL modulates mitochondrial functions including ATP synthesis. However, the biophysical mechanisms by which CL generates non-lamellar structures and the extent to which these structures contribute to ATP synthesis remain unknown. We hypothesized that CL and ATP synthase facilitate the formation of non-bilayer structures at the IMM to stimulate ATP synthesis. By using 1 H NMR and 31 P NMR techniques, we observed that increasing the temperature (8°C to 37°C), lowering the pH (3.0), or incubating intact mitochondria with CTII - an IMM-targeted toxin that increases the formation of immobilized non-bilayer structures - elevated the formation of non-bilayer structures to stimulate ATP synthesis. The F 0 sector of the ATP synthase complex can facilitate the formation of non-bilayer structures as incubating model membranes enriched with IMM-specific phospholipids with exogenous DCCD-binding protein of the F 0 sector (DCCD-BPF) elevated the formation of immobilized non-bilayer structures to a similar manner as CTII. Native PAGE assays revealed that CL, but not other anionic phospholipids, specifically binds to DCCD-BPF to promote the formation of stable lipid-protein complexes. Mechanistically, molecular docking studies identified two lipid binding sites for CL in DCCD-BPF. We propose a new model of ATP synthase regulation in which CL mediates the formation of non-bilayer structures that serve to cluster protons and ATP synthase complexes as a mechanism to enhance proton translocation to the F 0 sector, and thereby increase ATP synthesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Double-lock ratchet mechanism revealing the role of  SER-344 in FoF1 ATP synthase

    KAUST Repository

    Beke-Somfai, T.

    2011-03-07

    In a majority of living organisms, FoF1 ATP synthase performs the fundamental process of ATP synthesis. Despite the simple net reaction formula, ADP+Pi→ATP+H2O, the detailed step-by-step mechanism of the reaction yet remains to be resolved owing to the complexity of this multisubunit enzyme. Based on quantum mechanical computations using recent high resolution X-ray structures, we propose that during ATP synthesis the enzyme first prepares the inorganic phosphate for the γP-OADP bond-forming step via a double-proton transfer. At this step, the highly conserved αS344 side chain plays a catalytic role. The reaction thereafter progresses through another transition state (TS) having a planar ion configuration to finally form ATP. These two TSs are concluded crucial for ATP synthesis. Using stepwise scans and several models of the nucleotide-bound active site, some of the most important conformational changes were traced toward direction of synthesis. Interestingly, as the active site geometry progresses toward the ATP-favoring tight binding site, at both of these TSs, a dramatic increase in barrier heights is observed for the reverse direction, i.e., hydrolysis of ATP. This change could indicate a "ratchet" mechanism for the enzyme to ensure efficacy of ATP synthesis by shifting residue conformation and thus locking access to the crucial TSs.

  6. Imidazopyridine Compounds Inhibit Mycobacterial Growth by Depleting ATP Levels.

    Science.gov (United States)

    O'Malley, Theresa; Alling, Torey; Early, Julie V; Wescott, Heather A; Kumar, Anuradha; Moraski, Garrett C; Miller, Marvin J; Masquelin, Thierry; Hipskind, Philip A; Parish, Tanya

    2018-06-01

    The imidazopyridines are a promising new class of antitubercular agents with potent activity in vitro and in vivo We isolated mutants of Mycobacterium tuberculosis resistant to a representative imidazopyridine; the mutants had large shifts (>20-fold) in MIC. Whole-genome sequencing revealed mutations in Rv1339, a hypothetical protein of unknown function. We isolated mutants resistant to three further compounds from the series; resistant mutants isolated from two of the compounds had single nucleotide polymorphisms in Rv1339 and resistant mutants isolated from the third compound had single nucleotide polymorphisms in QcrB, the proposed target for the series. All the strains were resistant to two compounds, regardless of the mutation, and a strain carrying the QcrB T313I mutation was resistant to all of the imidazopyridine derivatives tested, confirming cross-resistance. By monitoring pH homeostasis and ATP generation, we confirmed that compounds from the series were targeting QcrB; imidazopyridines disrupted pH homeostasis and depleted ATP, providing further evidence of an effect on the electron transport chain. A representative compound was bacteriostatic against replicating bacteria, consistent with a mode of action against QcrB. The series had a narrow inhibitory spectrum, with no activity against other bacterial species. No synergy or antagonism was seen with other antituberculosis drugs under development. In conclusion, our data support the hypothesis that the imidazopyridine series functions by reducing ATP generation via inhibition of QcrB. Copyright © 2018 O'Malley et al.

  7. Stopping coal-fired electricity imports on smog days : a review of the OPA's proposed 250 MW demand response program

    International Nuclear Information System (INIS)

    Gibbons, J.

    2006-01-01

    This paper proposed an alternative to importing coal-fired electricity from the Ohio Valley on smog alert days in Ontario. It was suggested that the Ontario Power Authority (OPA) should pay large electricity consumers to shift some of their consumption from peak to off-peak hours. It was observed that demand response programs which pay consumers to shift demands to off-peak hours can provide multiple benefits to Ontario, including reduced air pollution on smog-alert days, a reduction in the spot price of electricity and reduced price volatility. In addition, demand response programs reduce the risk of blackouts and brownouts, as well as the need for new electricity generation and transmission infrastructure. It was noted that the Independent Electricity System Operator (IESO) and the OPA are planning to introduce demand response programs for the summer of 2006. However, the IESO's emergency load reduction program will be operated only during emergency situations to avoid the need for voltage reductions, while the OPA proposes to introduce a non-emergency demand response program which will be activated during most smog-alert days. Various amendments to the proposed program were suggested in this paper, including the establishment of price parity with coal-fired electricity imports; the provision of notification by 3 PM of the need for demand reductions the following day; no capping on the quantity of demand reductions that the OPA will purchase at a lower cost than electricity imports; and that the OPA's proposed Capacity Building Demand Response Program should proceed as quickly as possible without a pre-determined MW cap. 4 refs., 6 figs

  8. A proposed methodology for performing risk analysis of state radiation control programs

    International Nuclear Information System (INIS)

    Dornsife, W.P.

    1996-01-01

    This paper is comprised of viewgraphs from a conference presentation. Topics discussed include barriers to effective risk assessment and management, and real versus perceived risk for various radiation programs in the state of Pennsylvania. Calculation results for Pennsylvania are provided for low-level radioactive waste transportation risks, indoor radon risk, and cancer morbidity risk from x-rays. A methodology for prioritizing radiation regulatory programs based on risk is presented with calculations for various Pennsylvania programs

  9. Ballast water compliance monitoring: A new application for ATP

    Science.gov (United States)

    Lo Curto, A.; Stehouwer, P.; Gianoli, C.; Schneider, G.; Raymond, M.; Bonamin, V.

    2018-03-01

    The coming into force of the USCG ballast water regulations and the IMO ballast water management convention resulted in the development of several technologies approved for the treatment of ballast water. To ensure compliance of these technologies, the development of rapid and robust analysis methods was necessary. In collaboration with the SGS Group (Switzerland) and LuminUltra (Canada), Aqua-tools (France) has developed an innovative Ballast Water Treatment Monitoring (BWTM) kit for rapid onboard testing. The affordable kit provides results in less than 1 h, is easy to use and durable ensuring that the ballast water treatment system on the ship is fully compliant with the discharge standards upon arrival in port. The core of this method is a combination of high-quality reagents (lysis solution and ATP 2G Luminase™ enzyme) not inhibited by salinity and a patented fast homogenizing method for ATP extraction developed for a higher ATP recovery from zooplankton and phytoplankton. Compared to traditional analysis methods, the BWTM Kit provides fast and accurate results for all three fractions of microorganisms (≥ 50 μm, ≥ 10 ÷ < 50 μm and bacteria). Preliminary tests carried out in cooperation with SGS showed that the proposed method was able to detect onboard the efficiency of the treatment systems used. Compliance limits were established for all size fractions and a correlation between the standard methods (microscopy, plate count, MPN) and ATP was evaluated. The BWTM kit can provide a fast indication of compliance or gross exceedance. The rare borderline cases, when encountered, of course require additional confirmation.

  10. The thermodynamic efficiency of ATP synthesis in oxidative phosphorylation.

    Science.gov (United States)

    Nath, Sunil

    2016-12-01

    As the chief energy source of eukaryotic cells, it is important to determine the thermodynamic efficiency of ATP synthesis in oxidative phosphorylation (OX PHOS). Previous estimates of the thermodynamic efficiency of this vital process have ranged from Lehninger's original back-of-the-envelope calculation of 38% to the often quoted value of 55-60% in current textbooks of biochemistry, to high values of 90% from recent information theoretic considerations, and reports of realizations of close to ideal 100% efficiencies by single molecule experiments. Hence this problem has been reinvestigated from first principles. The overall thermodynamic efficiency of ATP synthesis in the mitochondrial energy transduction OX PHOS process has been found to lie between 40 and 41% from four different approaches based on a) estimation using structural and biochemical data, b) fundamental nonequilibrium thermodynamic analysis, c) novel insights arising from Nath's torsional mechanism of energy transduction and ATP synthesis, and d) the overall balance of cellular energetics. The torsional mechanism also offers an explanation for the observation of a thermodynamic efficiency approaching 100% in some experiments. Applications of the unique, molecular machine mode of functioning of F 1 F O -ATP synthase involving direct inter-conversion of chemical and mechanical energies in the design and fabrication of novel, man-made mechanochemical devices have been envisaged, and some new ways to exorcise Maxwell's demon have been proposed. It is hoped that analysis of the fundamental problem of energy transduction in OX PHOS from a fresh perspective will catalyze new avenues of research in this interdisciplinary field. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. The Role of ATP in the Regulation of NCAM Function

    DEFF Research Database (Denmark)

    Hübschmann, Martin; Skladchikova, Galina

    2008-01-01

    overlaps with the site of NCAM-FGFR interaction, and ATP is capable of disrupting NCAM-FGFR binding. This implies that NCAM signaling through FGFR can be regulated by ATP, which is supported by the observation that ATP can abrogate NCAM-induced neurite outgrowth. Finally, ATP can induce NCAM ectodomain...... shedding, possibly affecting the structural plasticity associated with learning and memory....

  12. Proposal for a Ph.D. Degree Program in Business Communication

    Science.gov (United States)

    Hildebrandt, Herbert

    1978-01-01

    Outlines procedures and assumptions for instituting a doctoral program in business communication. Lists general/specific requirements for enrollment, and suggests business-core and interdepartmental curricula. (RL)

  13. Proposal for a Wellness Clinician/Research Specialization for the Existing Degree Program, Master of Education in Physical Education.

    Science.gov (United States)

    Cardinal, Bradley J.; And Others

    Consistent with the Year 2000 National Health Promotion and Disease Prevention Objectives, this paper presents a proposal for a Wellness Clinician/Research specialization within the existing Master of Education in Physical Education degree program offered by the Division of Health, Physical Education, and Recreation at Wayne State University…

  14. 77 FR 33760 - Notice of Submission of Proposed Information Collection to OMB Public Housing Capital Fund Program

    Science.gov (United States)

    2012-06-07

    ... that are not subject to Independent Public Accountant (IPA) audit requirements. DATES: Comments Due... numerous PHAs that are not subject to Independent Public Accountant (IPA) audit requirements. Number of... Proposed Information Collection to OMB Public Housing Capital Fund Program AGENCY: Office of the Chief...

  15. 76 FR 59113 - Extension of the Due Date for Submitting Information on How to Structure Proposed New Program...

    Science.gov (United States)

    2011-09-23

    ... manufacturing research needs, and issue sub-awards to fund research by universities, government laboratories, and U.S. businesses. This initiative would support research and development (R&D) in advanced...-02] Extension of the Due Date for Submitting Information on How to Structure Proposed New Program...

  16. 76 FR 70828 - Proposed Information Collection (Mentor-Protégé Program Application and Reports) Activity...

    Science.gov (United States)

    2011-11-15

    ... DEPARTMENT OF VETERANS AFFAIRS [OMB Control No. 2900-0723] Proposed Information Collection (Mentor... in response to the notice. This notice solicits comments on information needed to establish a mentor... will be used to institute a mentor-prot[eacute]g[eacute] program whereby large businesses agree to...

  17. The Abbott School Construction Program: Report on the NJ Department of Education Proposed Regulations on Long-Range Facilities Plans

    Science.gov (United States)

    Ponessa, Joan

    2004-01-01

    This report on Long Range Facilities Plans (LRFPs) analyzes regulations proposed by the New Jersey Department of Education (NJDOE) to implement the Educational Facilities Construction and Financing Act. (EFCFA). EFCFA, which authorizes and governs New Jersey's public school construction program, was enacted in July 2000 to implement the State…

  18. Duchenne muscular dystrophy: normal ATP turnover in cultured cells

    International Nuclear Information System (INIS)

    Fox, I.H.; Bertorini, T.; Palmieri, G.M.A.; Shefner, R.

    1986-01-01

    This paper examines ATP metabolism in cultured muscle cells and fibroblasts from patients with Duchenne dystrophy. ATP and ADP levels were the same in cultured cells from normal subjects and patients and there was no difference in ATP synthesis or degradation. The ATP synthesis was measured by the incorporation of C 14-U-adenine into aTP and ADP. although there was a significant decrease in radioactively labelled ATP after incubation with deoxyglucose in Duchenne muscle cells, there was no difference in ATP concentration of ADP metabolism

  19. 75 FR 27789 - Proposed Collection; Comment Request; Application for the Pharmacology Research Associate Program

    Science.gov (United States)

    2010-05-18

    ... comment on proposed data collection projects, the National Institute of General Medical Sciences (NIGMS), the National Institutes of Health (NIH) will publish periodic summaries of proposed projects to be... develop leaders in pharmacological research for key positions in academic, industrial, and Federal...

  20. 76 FR 53844 - National Dairy Promotion and Research Program; Invitation To Submit Comments on Proposed...

    Science.gov (United States)

    2011-08-30

    ... DEPARTMENT OF AGRICULTURE Agricultural Marketing Service 7 CFR Part 1150 [Document No. AMS-DA-11... Proposed Amendments to the Order AGENCY: Agricultural Marketing Service, USDA. ACTION: Proposed rule... with the Regulatory Flexibility Act (5 U.S.C. 601- 612), the Agricultural Marketing Service has...

  1. 78 FR 22361 - 60-Day Notice of Proposed Information Collection: PEPFAR Program Expenditures

    Science.gov (United States)

    2013-04-15

    .... Summaries of these data provide key information about program costs under PEPFAR on a global level. Applying...-0208 Type of Request: Revision of a Currently Approved Collection Originating Office: Office of the U.S... Economics Work Group supporting PEPFAR has added reporting of expenditures by program area to the current...

  2. 75 FR 36120 - Proposed Information Collection Request Submitted for Public Comment and Recommendations; Program...

    Science.gov (United States)

    2010-06-24

    ... Submitted for Public Comment and Recommendations; Program To Prevent Smoking Underground and in Hazardous... mine operators are required to develop programs to prevent persons from carrying smoking materials, matches, or lighters underground and to prevent smoking in hazardous areas, such as in or around oil...

  3. 76 FR 9376 - Proposed Extension of Existing Information Collection on Qualification/Certification Program and...

    Science.gov (United States)

    2011-02-17

    ... Extension of Existing Information Collection on Qualification/Certification Program and Man Hoist Operators... 77.107-1 on Qualification/Certification Program and Man Hoist Operators Physical Fitness. DATES: All... Labor or Secretary of Health and Human Services must make frequent inspections and investigations in...

  4. 77 FR 16319 - Proposed Renewal; Comment Request; Anti-Money Laundering Programs for Various Financial Institutions

    Science.gov (United States)

    2012-03-20

    ...; Anti-Money Laundering Programs for Various Financial Institutions AGENCY: Financial Crimes Enforcement... certain insurance companies to develop and implement written anti-money laundering programs reasonably designed to prevent those financial institutions from being used to facilitate money laundering and the...

  5. 76 FR 79650 - Proposed Information Collection; Comment Request; Survey of Income and Program Participation...

    Science.gov (United States)

    2011-12-22

    ...' participation in government programs as well as prior labor force patterns of household members. These... were interviewed. We estimate that each household contains 2.1 people, age 15 years or older, yielding... of Income and Program Participation (SIPP) Wave 13 of the 2008 Panel AGENCY: U.S. Census Bureau...

  6. 78 FR 23777 - Notice of Proposed Information Collection: Comment Request: HUD-Administered Small Cities Program...

    Science.gov (United States)

    2013-04-22

    ... Information Collection: Comment Request: HUD- Administered Small Cities Program Performance Assessment Report... program provides HUD with financial and physical development status of each activity funded. These reports[email protected] fax: 202-395-5806. FOR FURTHER INFORMATION CONTACT: Colette Pollard, Reports...

  7. 77 FR 5717 - National Organic Program; Proposed Amendment to the National List of Allowed and Prohibited...

    Science.gov (United States)

    2012-02-06

    ... the OFPA (7 U.S.C. 6507(b)(2)), a State organic certification program may contain additional... the State and for the certification of organic farm and handling operations located within the State... inconsistent with the organic certification program established under this title. The OFPA also provides that...

  8. 78 FR 25760 - Proposed Information Collection; Urban Park and Recreation Recovery Program Grants

    Science.gov (United States)

    2013-05-02

    ... procedures for awarding grants. The three types of grants available under the program are: Rehabilitation..., and institutional arrangements of the community. The RAP consists of two sections, which are the... maintenance; employment and training; programs and services; rehabilitation of existing facilities; and the...

  9. 78 FR 28242 - Proposed Information Collection; Cleanup Program for Accumulations of Coal and Float Coal Dusts...

    Science.gov (United States)

    2013-05-14

    ... Program for Accumulations of Coal and Float Coal Dusts, Loose Coal, and Other Combustibles AGENCY: Mine... collection for developing and updating a cleanup program for accumulations of coal and float coal dusts, loose coal, and other combustibles in underground coal mines. DATES: All comments must be postmarked or...

  10. Blockade of Extracellular ATP Effect by Oxidized ATP Effectively Mitigated Induced Mouse Experimental Autoimmune Uveitis (EAU.

    Directory of Open Access Journals (Sweden)

    Ronglan Zhao

    Full Text Available Various pathological conditions are accompanied by ATP release from the intracellular to the extracellular compartment. Extracellular ATP (eATP functions as a signaling molecule by activating purinergic P2 purine receptors. The key P2 receptor involved in inflammation was identified as P2X7R. Recent studies have shown that P2X7R signaling is required to trigger the Th1/Th17 immune response, and oxidized ATP (oxATP effectively blocks P2X7R activation. In this study we investigated the effect of oxATP on mouse experimental autoimmune uveitis (EAU. Our results demonstrated that induced EAU in B6 mice was almost completely abolished by the administration of small doses of oxATP, and the Th17 response, but not the Th1 response, was significantly weakened in the treated mice. Mechanistic studies showed that the therapeutic effects involve the functional change of a number of immune cells, including dendritic cells (DCs, T cells, and regulatory T cells. OxATP not only directly inhibits the T cell response; it also suppresses T cell activation by altering the function of DCs and Foxp3+ T cell. Our results demonstrated that inhibition of P2X7R activation effectively exempts excessive autoimmune inflammation, which may indicate a possible therapeutic use in the treatment of autoimmune diseases.

  11. Extracellular ATP in the Exocrine Pancreas – ATP Release, Signalling and Metabolism

    DEFF Research Database (Denmark)

    Kowal, Justyna Magdalena

    release. So far, the contribution of duct cells in purinergic signalling has never been studied. This work presents that both acinar and duct cells are sources of extracellular ATP in the exocrine pancreas. Here we show that duct cells release ATP in response to several physiological......ATP plays an important role as an autocrine/paracrine signalling molecule, being released from a number of tissues, in response to physiological and pathophysiological stimuli. Released ATP induces Ca2+ - and/or cAMP - dependent cellular responses via activation of ubiquitously expressed P2X and P2......, particularly during Ca2+ stress conditions. In conclusion, these studies demonstrate a complex regulation of purinergic signalling in exocrine pancreas. A crucial role for duct cells in mediating extracellular nucleotides homeostasis, involving ATP release, subsequent hydrolysis and conversion via...

  12. Proposed plan for public benefit programs funded by System Benefits Charge

    International Nuclear Information System (INIS)

    1998-01-01

    As the electric industry in New York State moves through deregulation toward retail competition, it will be important to ensure the vital public benefit programs of energy efficiency, research and development, low income services, and environmental protection. The Public Service Commission's (PSC) Opinion No. 98-3, effective January 30, 1998, established a system for funding such programs with a non-passable System Benefits Charge (SBC) and designated the New York State Energy Research and Development Authority (NYSERDA) as the administrator of the statewide SBC-funded public benefit programs

  13. 77 FR 69585 - Greenhouse Gas Reporting Program: Proposed Amendments and Confidentiality Determinations for...

    Science.gov (United States)

    2012-11-20

    ... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 98 [EPA-HQ-OAR-2011-0028; FRL-9753-2] Greenhouse Gas... announcing an extension of the public comment period for the proposed rule titled ``Greenhouse Gas Reporting... [[Page 69586

  14. 77 FR 43428 - Financial Management Service; Proposed Collection of Information: Minority Bank Deposit Program...

    Science.gov (United States)

    2012-07-24

    ... DEPARTMENT OF THE TREASURY Fiscal Service Financial Management Service; Proposed Collection of... Management Service, Fiscal Service, Treasury. ACTION: Notice and Request for comments. SUMMARY: The Financial... collection. By this notice, the Financial Management Service solicits comments concerning form FMS 3144...

  15. Different training programs for the transport of radioactive goods proposed by the INSTN

    International Nuclear Information System (INIS)

    Kimmel, O.

    2004-01-01

    To meet the statutory requirements of the ADR pertaining to training, the INSTN (National Institute for Nuclear Sciences and Technology) proposes different courses on the transport of radioactive materials

  16. 78 FR 77204 - Proposed Information Collection (VA National Veterans Sports Programs and Special Event Surveys...

    Science.gov (United States)

    2013-12-20

    ... AGENCY: Office of Public & Intergovernmental Affairs, Department of Veterans Affairs. ACTION: Notice. SUMMARY: The Office of Public Affairs (OPA), Department of Veterans Affairs (VA), is announcing an... DEPARTMENT OF VETERANS AFFAIRS [OMB Control No. 2900-NEW] Proposed Information Collection (VA...

  17. Selection methodology for LWR safety programs and proposals. Volume 2. Methodology application

    International Nuclear Information System (INIS)

    Ritzman, R.L.; Husseiny, A.A.

    1980-08-01

    The results of work done to update and apply a methodology for selecting (prioritizing) LWR safety technology R and D programs are described. The methodology is based on multiattribute utility (MAU) theory. Application of the methodology to rank-order a group of specific R and D programs included development of a complete set of attribute utility functions, specification of individual attribute scaling constants, and refinement and use of an interactive computer program (MAUP) to process decision-maker inputs and generate overall (multiattribute) program utility values. The output results from several decision-makers are examined for consistency and conclusions and recommendations regarding general use of the methodology are presented. 3 figures, 18 tables

  18. 77 FR 14348 - Proposed Information Collection; Comment Request; Marine Recreational Information Program

    Science.gov (United States)

    2012-03-09

    ... Collection; Comment Request; Marine Recreational Information Program AGENCY: National Oceanic and Atmospheric... for revision of a current information collection. Marine recreational anglers are surveyed to collect catch and effort data, fish biology data, and angler socioeconomic characteristics. These data are...

  19. 78 FR 72600 - Proposed Priorities, Requirements, and Definitions-Charter Schools Program (CSP) Grants for...

    Science.gov (United States)

    2013-12-03

    ... financial assistance for the planning, program design, and initial implementation of charter schools; (2.... Charter schools are explicitly designed to have the autonomy to employ innovative, promising [[Page 72601

  20. 78 FR 21912 - Proposed Information Collection; Comment Request; Crab Rationalization (CR) Program: Annual Report

    Science.gov (United States)

    2013-04-12

    ... consolidation, absentee quota share (QS) ownership, and changes in crew compensation as some of the program's... financial impacts of high lease rates, the amount of any lease payments charged to crews could be limited or...

  1. Proposing an Aggregate Production Planning Model by Goal Programming Approach, a Case Study

    Directory of Open Access Journals (Sweden)

    Mansoureh Farzam Rad

    2014-06-01

    Full Text Available Production planning is one of the most important functions in the process of production management. Production planning in the intermediate range of time is termed as aggregate production planning (APP. Aggregate production planning is an important upper level planning activity in a production management system. The present study tries to suggest an aggregate production planning model for products of Hafez tile factory during one year. Due to this fact that the director of the company seeks 3 main objectives to determine the optimal production rate, the linear goal planning method was employed. After solving the problem, in order to examine the efficiency and the distinctiveness of this method in compare to linear programming, the problem was modeled just by considering one objective then was solved by linear programming approach. The findings revealed the goal programming with multi objectives resulted more appropriate solution rather than linear programming with just one objective.

  2. 77 FR 14340 - Proposed Information Collection; Comment Request; Broadband Technology Opportunities Program...

    Science.gov (United States)

    2012-03-09

    ..., broadband service by public safety agencies; and (5) To stimulate the demand for broadband, economic growth, and job creation. OMB also requires agencies administering grant programs to [[Page 14341

  3. Astrophysical research at Lawrence Livermore Laboratory, proposal for a formal program

    Energy Technology Data Exchange (ETDEWEB)

    Lokke, W.A.; Tarter, C.B.

    1979-12-01

    Basic research is often characterized as self-directed, moving on its own timescale, spurred by the unexpected. An effective, organized basic astrophysics research program does not have to be a contradiction in terms. A broadly chartered, long-range LLL Astrophysics Research Program, created and recognized by LLL management, can benefit the general scientific community, stimulate the staff, maintain important capability, and enrich the Laboratory.

  4. Astrophysical research at Lawrence Livermore Laboratory, proposal for a formal program

    International Nuclear Information System (INIS)

    Lokke, W.A.; Tarter, C.B.

    1979-12-01

    Basic research is often characterized as self-directed, moving on its own timescale, spurred by the unexpected. An effective, organized basic astrophysics research program does not have to be a contradiction in terms. A broadly chartered, long-range LLL Astrophysics Research Program, created and recognized by LLL management, can benefit the general scientific community, stimulate the staff, maintain important capability, and enrich the Laboratory

  5. Preoperative multidisciplinary program for bariatric surgery: a proposal for the Brazilian Public Health System

    Directory of Open Access Journals (Sweden)

    Elinton Adami CHAIM

    Full Text Available ABSTRACT BACKGROUND Bariatric surgery has become the gold standard treatment for morbid obesity, but access to surgery remains difficult and low compliance to postoperative follow-up is common. To improve outcomes, enable access and optimize follow-up, we developed a multidisciplinary preoperative approach for bariatric surgery. OBJECTIVE To determine the impact of this program in the outcomes of bariatric surgery in the Brazilian public health system. METHODS A prospective evaluation of the individuals who underwent a preoperative multidisciplinary program for bariatric surgery and comparison of their surgical outcomes with those observed in the prospectively collected historical database of the individuals who underwent surgery before the beginning of the program. RESULTS There were 176 individuals who underwent the multidisciplinary program and 226 who did not. Individuals who underwent the program had significantly lower occurrence of the following variables: hospital stay; wound dehiscence; wound infection; pulmonary complications; anastomotic leaks; pulmonary thromboembolism; sepsis; incisional hernias; eventrations; reoperations; and mortality. Both loss of follow-up and weight loss failure were also significantly lower in the program group. CONCLUSION The adoption of a comprehensive preoperative multidisciplinary approach led to significant improvements in the postoperative outcomes and also in the compliance to the postoperative follow-up. It represents a reproducible and potentially beneficial approach within the context of the Brazilian public health system.

  6. Nuclear genetic defects of mitochondrial ATP synthase

    Czech Academy of Sciences Publication Activity Database

    Hejzlarová, Kateřina; Mráček, Tomáš; Vrbacký, Marek; Kaplanová, Vilma; Karbanová, Vendula; Nůsková, Hana; Pecina, Petr; Houštěk, Josef

    2014-01-01

    Roč. 63, Suppl.1 (2014), S57-S71 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP303/11/0970; GA ČR GAP303/12/1363; GA MZd(CZ) NT12370; GA MZd(CZ) NT14050 Grant - others:Univerzita Karlova(CZ) 370411 Institutional support: RVO:67985823 Keywords : mitochondrial diseases * TMEM70 * ATPAF1 * ATP5A1 * ATP5E Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.293, year: 2014

  7. Evolutionary relationships of ATP-Binding Cassette (ABC) uptake porters.

    Science.gov (United States)

    Zheng, Wei Hao; Västermark, Åke; Shlykov, Maksim A; Reddy, Vamsee; Sun, Eric I; Saier, Milton H

    2013-05-06

    The ATP-Binding Cassette (ABC) functional superfamily includes integral transmembrane exporters that have evolved three times independently, forming three families termed ABC1, ABC2 and ABC3, upon which monophyletic ATPases have been superimposed for energy-coupling purposes [e.g., J Membr Biol 231(1):1-10, 2009]. The goal of the work reported in this communication was to understand how the integral membrane constituents of ABC uptake transporters with different numbers of predicted or established transmembrane segments (TMSs) evolved. In a few cases, high resolution 3-dimensional structures were available, and in these cases, their structures plus primary sequence analyses allowed us to predict evolutionary pathways of origin. All of the 35 currently recognized families of ABC uptake proteins except for one (family 21) were shown to be homologous using quantitative statistical methods. These methods involved using established programs that compare native protein sequences with each other, after having compared each sequence with thousands of its own shuffled sequences, to gain evidence for homology. Topological analyses suggested that these porters contain numbers of TMSs ranging from four or five to twenty. Intragenic duplication events occurred multiple times during the evolution of these porters. They originated from a simple primordial protein containing 3 TMSs which duplicated to 6 TMSs, and then produced porters of the various topologies via insertions, deletions and further duplications. Except for family 21 which proved to be related to ABC1 exporters, they are all related to members of the previously identified ABC2 exporter family. Duplications that occurred in addition to the primordial 3 → 6 duplication included 5 → 10, 6 → 12 and 10 → 20 TMSs. In one case, protein topologies were uncertain as different programs gave discrepant predictions. It could not be concluded with certainty whether a 4 TMS ancestral protein or a 5 TMS ancestral protein

  8. Escherichia coli contains a soluble ATP-dependent protease (Ti) distinct from protease La

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, B.J.; Park, W.J.; Chung, C.H.; Goldberg, A.L.

    1987-08-01

    The energy requirement for protein breakdown in Escherichia coli has generally been attributed to the ATP-dependence of protease La, the lon gene product. The authors have partially purified another ATP-dependent protease from lon/sup -/ cells that lack protease La (as shown by immunoblotting). This enzyme hydrolyzes (/sup 3/H)methyl-casein to acid-soluble products in the presence of ATP and Mg/sup 2 +/. ATP hydrolysis appears necessary for proteolytic activity. Since this enzyme is inhibited by diisopropyl fluorophosphate, it appears to be a serine protease, but it also contains essential thiol residues. They propose to name this enzyme protease Ti. It differs from protease La in nucleotide specificity, inhibitor sensitivity, and subunit composition. On gel filtration, protease Ti has an apparent molecular weight of 370,000. It can be fractionated by phosphocellulose chromatography or by DEAE chromatography into two components with apparent molecular weights of 260,000 and 140,000. When separated, they do not show preteolytic activity. One of these components, by itself, has ATPase activity and is labile in the absence of ATP. The other contains the diisopropyl fluorophosphate-sensitive proteolytic site. These results and the similar findings of Katayama-Fujimura et al. indicate that E. coli contains two ATP-hydrolyzing proteases, which differ in many biochemical features and probably in their physiological roles.

  9. Escherichia coli contains a soluble ATP-dependent protease (Ti) distinct from protease La

    International Nuclear Information System (INIS)

    Hwang, B.J.; Park, W.J.; Chung, C.H.; Goldberg, A.L.

    1987-01-01

    The energy requirement for protein breakdown in Escherichia coli has generally been attributed to the ATP-dependence of protease La, the lon gene product. The authors have partially purified another ATP-dependent protease from lon - cells that lack protease La (as shown by immunoblotting). This enzyme hydrolyzes [ 3 H]methyl-casein to acid-soluble products in the presence of ATP and Mg 2+ . ATP hydrolysis appears necessary for proteolytic activity. Since this enzyme is inhibited by diisopropyl fluorophosphate, it appears to be a serine protease, but it also contains essential thiol residues. They propose to name this enzyme protease Ti. It differs from protease La in nucleotide specificity, inhibitor sensitivity, and subunit composition. On gel filtration, protease Ti has an apparent molecular weight of 370,000. It can be fractionated by phosphocellulose chromatography or by DEAE chromatography into two components with apparent molecular weights of 260,000 and 140,000. When separated, they do not show preteolytic activity. One of these components, by itself, has ATPase activity and is labile in the absence of ATP. The other contains the diisopropyl fluorophosphate-sensitive proteolytic site. These results and the similar findings of Katayama-Fujimura et al. indicate that E. coli contains two ATP-hydrolyzing proteases, which differ in many biochemical features and probably in their physiological roles

  10. Arabidopsis ATP A2 peroxidase. Expression and high-resolution structure of a plant peroxidase with implications for lignification

    DEFF Research Database (Denmark)

    Ostergaard, L; Teilum, K; Mirza, O

    2000-01-01

    Lignins are phenolic biopolymers synthesized by terrestrial, vascular plants for mechanical support and in response to pathogen attack. Peroxidases have been proposed to catalyse the dehydrogenative polymerization of monolignols into lignins, although no specific isoenzyme has been shown...... to be involved in lignin biosynthesis. Recently we isolated an extracellular anionic peroxidase, ATP A2, from rapidly lignifying Arabidopsis cell suspension culture and cloned its cDNA. Here we show that the Atp A2 promoter directs GUS reporter gene expression in lignified tissues of transgenic plants. Moreover......-coumaryl and coniferyl alcohols are preferred by ATP A2, while the oxidation of sinapyl alcohol will be sterically hindered in ATP A2 as well as in all other plant peroxidases due to an overlap with the conserved Pro-139. We suggest ATP A2 is involved in a complex regulation of the covalent cross-linking in the plant...

  11. Tracking protons from respiratory chain complexes to ATP synthase c-subunit: The critical role of serine and threonine residues.

    Science.gov (United States)

    Panfoli, Isabella; Ponassi, Marco; Ravera, Silvia; Calzia, Daniela; Beitia, Maider; Morelli, Alessandro; Rosano, Camillo

    2017-01-22

    F 1 F o -ATP synthase is a multisubunit enzyme responsible for the synthesis of ATP. Among its multiple subunits (8 in E. coli, 17 in yeast S. cerevisiae, 16 in vertebrates), two subunits a and c are known to play a central role controlling the H + flow through the inner mitochondrial membrane which allows the subsequent synthesis of ATP, but the pathway followed by H + within the two proteins is still a matter of debate. In fact, even though the structure of ATP synthase is now well defined, the molecular mechanisms determining the function of both F 1 and F O domains are still largely unknown. In this study, we propose a pathway for proton migration along the ATP synthase by hydrogen-bonded chain mechanism, with a key role of serine and threonine residues, by X-ray diffraction data on the subunit a of E. coli Fo. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Prioritization of proposed waste management construction projects for the Waste Management program within the Department of Energy

    International Nuclear Information System (INIS)

    Johnson, J.V.

    1995-01-01

    A prioritization process is used to evaluate and rank proposed construction projects within the Department of Energy's Waste Management program. The process is used to determine which projects should proceed with conceptual design activities. The proposed construction projects are evaluated against a set of criteria which reflect Waste Management priorities. A management review team ranks and scores the projects thereby generating a prioritized list of projects. Despite decreasing budgets and changing political climates, the process has been a successful decision-aiding tool for selecting construction projects to carry out the Waste Management mission within the Department of Energy

  13. The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory & urological disorders

    Directory of Open Access Journals (Sweden)

    Anthony eFord

    2013-12-01

    Full Text Available A sensory role for ATP was proposed long before general acceptance of its extracellular role. ATP activates & sensitizes signal transmission at multiple sites along the sensory axis, across multiple synapses. P2X & P2Y receptors mediate ATP modulation of sensory pathways & participate in dysregulation, where ATP action directly on primary afferent neurons (PANs, linking receptive field to CNS, has received much attention. Many PANs, especially C-fibers, are activated by ATP, via P2X3-containing trimers. P2X3 knock-out mice & knock-down in rats led to reduced nocifensive activity & visceral reflexes, suggesting that antagonism may offer benefit in sensory disorders. Recently, drug-like P2X3 antagonists, active in a many inflammatory & visceral pain models, have emerged. Significantly, these compounds have no overt CNS action & are inactive versus acute nociception. Selectively targeting ATP sensitization of PANs may lead to therapies that block inappropriate chronic signals at their source, decreasing drivers of peripheral & central wind-up, yet leaving defensive nociceptive and brain functions unperturbed. This article reviews this evidence, focusing on how ATP sensitization of PANs in visceral hollow organs primes them to chronic discomfort, irritation & pain (symptoms as well as exacerbated autonomic reflexes (signs, & how the use of isolated organ-nerve preparations has revealed this mechanism. Urinary & airways systems share many features: dependence on continuous afferent traffic to brainstem centers to coordinate efferent autonomic outflow; loss of descending inhibitory influence in functional & sensory disorders; dependence on ATP in mediating sensory responses to diverse mechanical and chemical stimuli; a mechanistically overlapping array of existing medicines for pathological conditions. These similarities may also play out in terms of future treatment of signs & symptoms, in the potential for benefit of P2X3 antagonists.

  14. 78 FR 4425 - Notice of Proposed Information Collection: Comment Request; Debt Resolution Program

    Science.gov (United States)

    2013-01-22

    ... amount due must submit a Personal Financial Statement and Settlement Offer. HUD uses the information to... Settlement Offer. HUD uses the information to analyze debtors' financial positions and then approve... Information and Proposed Use HUD is required to collect debt owed to the agency. As part of the collection...

  15. 77 FR 41191 - Proposed Collection; Comment Request: Effectiveness of the NIH Curriculum Supplements Programs

    Science.gov (United States)

    2012-07-12

    ... supplements in presenting science in a more engaging and interactive way. The supplements help K-12 educators teach science by featuring the latest NIH research and utilized research-based instructional methods. A... comment on proposed data collection projects, the Office of Science Education, the National Institutes of...

  16. 76 FR 41178 - Medicare Program; Proposed Changes to the Hospital Inpatient Prospective Payment Systems for...

    Science.gov (United States)

    2011-07-13

    ... Prospective Payment Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective Payment...; Proposed Changes to the Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective Payment System and Fiscal Year 2012 Rates'' which appeared in the...

  17. 76 FR 43657 - Proposed Information Collection; Comment Request; Project 25 Compliance Assessment Program...

    Science.gov (United States)

    2011-07-21

    ... DEPARTMENT OF COMMERCE National Institute of Standards and Technology Proposed Information... via the Internet at [email protected] ). SUPPLEMENTARY INFORMATION: I. Abstract The September 11... collection techniques or other forms of information technology. Comments submitted in response to this notice...

  18. 75 FR 1555 - National Organic Program; Proposed Amendments to the National List of Allowed and Prohibited...

    Science.gov (United States)

    2010-01-12

    ... in organic crop production. Tetracycline is a broad-spectrum antibiotic for control of bacteria... also antibiotics used in human and animal drugs. Per the Federal Food, Drug, and Cosmetic Act (FFDCA... material in organic crop production. Consistent with the recommendations from the NOSB, this proposed rule...

  19. 77 FR 56857 - Notice of Proposed Information Collection for Public Comment; Public Housing Mortgage Program and...

    Science.gov (United States)

    2012-09-14

    ... of the loan resulting from the mortgage or security interest are used for low-income housing uses... mortgage or security interest in any public housing real estate or other assets, a proposal must be submitted to HUD. After approval and execution of any legal documents associated with the loan and related...

  20. 75 FR 23851 - Medicare Program; Proposed Changes to the Hospital Inpatient Prospective Payment Systems for...

    Science.gov (United States)

    2010-05-04

    ... Diagnoses for Current HACs g. Preliminary RTI Analysis of Estimated Net Savings for Current HACs h... MIEA-TRHCA a. Reclassification Average Hourly Wage Comparison Criteria b. Budget Neutrality Adjustment....--Proposed Rural Floor Budget Neutrality Factors for Acute Care Hospitals--FY 2011 Table 4D-2.--Urban Areas...

  1. 76 FR 72003 - Proposed Collection, Laura Bush 21st Century Librarian Grant Program Evaluation

    Science.gov (United States)

    2011-11-21

    ... Services Act, Public Law 104-208 and is the primary source of federal support for the nation's 123,000... Century Librarian Grant Program Evaluation AGENCY: Institute of Museum and Library Services, National Foundation for the Arts and the Humanities. ACTION: Notice, request for comments, collection of information...

  2. 78 FR 35054 - Proposed Collection; Comment Request; Program to Prevent Smoking in Hazardous Areas (Pertains to...

    Science.gov (United States)

    2013-06-11

    ...; Program to Prevent Smoking in Hazardous Areas (Pertains to Underground Coal Mines) AGENCY: Mine Safety and... carrying smoking materials, matches, or lighters underground and to prevent smoking in hazardous areas... Act), 30 U.S.C. 877(c), and 30 CFR 75.1702 prohibits persons from smoking or carrying smoking...

  3. Proposal of a research and development program for cerebral tumor treatment by neutron capture

    International Nuclear Information System (INIS)

    Silva, M.M. da

    1992-01-01

    The researches related to the Boron Neutron Capture Therapy, that were developed at Nuclear Energetic Institute (IPEN/CNEN-SP) and the Coordination for Special Projects (COPESP) are described. A coordinate development program is presented for constructing of an installation, with the purpose of routine utilization of this technique. (C.G.C.)

  4. Proposal of a control and quality guarantee program in radiotherapy and radiodiagnosis

    International Nuclear Information System (INIS)

    Tovar Rodas, J.A.

    1998-01-01

    In Guatemala, as regards guarantee and control of quality in the radiotherapy and radiodiagnostic areas, doesn't have until the moment, properly established, an action plan to carry out in systematic form, a program that it satisfies the design requirements and operation in an installation of this nature. However, it is well-known that the techniques that involve the employment of the ionizing radiations are powerful tools for their applications in industry, investigation and medicine; their use should be optimized and the associate risks should be evaluated to prevent them and to limit them. At the moment, the first actions of a guarantee program and quality control are carried out in the radiotherapy area for the intervention of the Secondary Laboratory of Dosimetric Calibration, but the quick growth of this area and the high number of radiodiagnosis facilities that work in the country, they outline the necessity to develop a methodology that solves the problem that is presented by the lack of controls of quality in these practices partly. The present work, presents in first plane the objectives, antecedents, forms of development, available resources and the necessities that are had in each area for the setting in march of the Quality Guarantee Program in Radiotherapy and of the Quality Control Program in Radiodiagnosis

  5. 77 FR 73493 - Notice of Proposed Information Collection: Comment Request Family Self-Sufficiency Program...

    Science.gov (United States)

    2012-12-10

    .... DATES: Comments Due Date: February 8, 2013. ADDRESSES: Interested persons are invited to submit comments... model is needed because participant self-selection into FSS limits the ability to know whether program.... Tracking survey sample 3,000 1 Maximum of 1 hour over 3,000 hours. the tracking period, mainly to update...

  6. 75 FR 26283 - Proposed Collection, Submission for OMB Review, Museums for America Grant Program Evaluation

    Science.gov (United States)

    2010-05-11

    ... Review, Museums for America Grant Program Evaluation AGENCY: Institute of Museum and Library Services..., Submission for OMB Review. SUMMARY: The Institute of Museum and Library Services announces the following... functions of the agency, including whether the information will have practical utility; Evaluate the...

  7. 77 FR 45716 - Proposed Information Collection (Foreign Medical Program); Comment Request

    Science.gov (United States)

    2012-08-01

    ... solicits comments on information needed to reimburse healthcare providers for medical services provided to... quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of... techniques or the use of other forms of information technology. Titles: a. Foreign Medical Program...

  8. 77 FR 16118 - Proposed Renewal Without Change; Comment Request; Customer Identification Programs for Various...

    Science.gov (United States)

    2012-03-19

    ... to prevent those financial institutions from being used to facilitate money laundering and the... and FinCEN's implementing regulations, or to guard against money laundering, which includes imposing anti-money laundering (``AML'') program requirements on financial institutions.\\4\\ \\1\\ The BSA is...

  9. 76 FR 24457 - Proposed Information Collection; Comment Request; Survey of Income and Program Participation...

    Science.gov (United States)

    2011-05-02

    ... around a central ``core'' of labor force and income questions that remain fixed throughout the life of... obtaining information on household members' participation in government programs as well as prior labor... contains 2.1 people, age 15 years or older, yielding approximately 94,500 person-level interviews in Wave 1...

  10. 76 FR 14901 - Proposed Information Collection; Comment Request; Participant Application, Program Exit...

    Science.gov (United States)

    2011-03-18

    ... application, on the program's English-language Web site at http://www.trade.gov/sabit , and also on the Russian-language Web site at http://www.sabitprogram.org , if applicable. Pursuant to section 632(a) of... downloaded from the SABIT English and Russian language Web sites at http://www.trade.gov/sabit and http://www...

  11. 78 FR 48441 - Office of Urban Indian Health Programs Proposed Single Source Grant With Native American...

    Science.gov (United States)

    2013-08-08

    ... Indians and Alaska Natives (AI/ AN) residing in the Boston metropolitan area. This program is authorized.... Emergency Response: We have learned from the past and are better prepared for the future. There is an ethic...) those recognized now or in the future by the State in which they reside; or (b) Is a descendant, in the...

  12. 76 FR 63017 - Medicare Program; Proposed Changes to the Medicare Advantage and the Medicare Prescription Drug...

    Science.gov (United States)

    2011-10-11

    ... (Sec. 423.2300) b. Definitions (Sec. 423.2305) (1) Applicable Beneficiary (2) Applicable Drug (3... marketing, including agent/broker training; payments to MA organizations based on quality ratings; standards... program; payment rules for non-contract health care providers; extending current network adequacy...

  13. 76 FR 24041 - Notice of Proposed Information Collection: Comment Request; HUD Housing Counseling Program-Agency...

    Science.gov (United States)

    2011-04-29

    ... a HUD-approved intermediary or multi-state organization, or be a state housing finance agency or affiliate or sub grantee of a state housing finance agency. Participation in the program entails meeting.... Additionally, this information helps HUD staff to assess whether participating organizations are meeting basic...

  14. 77 FR 28854 - Proposed Information Collection; Comment Request; Coastal Zone Management Program Administration

    Science.gov (United States)

    2012-05-16

    ... because of the importance of U.S. coastal areas, the U.S. Congress passed the Coastal Zone Management Act... (CZMP) Performance Management System; revise assessment document and multi-year strategy; submit.... Method of Collection Respondents have a choice of electronic or paper formats for submitting program...

  15. 75 FR 39206 - Proposed Information Collection; Comment Request; International Buyer Program Application and...

    Science.gov (United States)

    2010-07-08

    ... compared to the attendance when not supported by program. The criteria used to select these shows are...-0151. Form Number(s): ITA-4014P and ITA-4102P. Type of Review: Regular submission. Affected Public... technology. Comments submitted in response to this notice will be summarized and/or included in the request...

  16. 78 FR 52100 - National Organic Program; Proposed Amendments to the National List of Allowed and Prohibited...

    Science.gov (United States)

    2013-08-22

    .... 6503 through 6507) from creating certification programs to certify organic farms or handling operations... requirements of the OFPA. Pursuant to the OFPA (7 U.S.C. 6507(b)(2)), a State organic certification [[Page... produced agricultural products that are produced in the State and for the certification of organic farm and...

  17. 78 FR 30930 - Proposed Collection; 60-Day Comment Request: Generic Clearance To Support Programs and...

    Science.gov (United States)

    2013-05-23

    ..., mechanical, or other technological collection techniques or other forms of information technology. To Submit... purposes (e.g., an application) or to monitor or improve a program. These ICs may involve little if any... and comments to this request. Along with the analysis, NCI's ongoing education and outreach effort has...

  18. 76 FR 7570 - Proposed Collection; Comment Request; National Institutes of Health Loan Repayment Programs

    Science.gov (United States)

    2011-02-10

    ... years for the General Research Loan Repayment Program (LRP)) in research areas supporting the mission and priorities of the NIH. The AIDS Research LRP (AIDS-LRP) is authorized by section 487A of the... the equivalent, who perform biomedical or behavioral research in NIH intramural laboratories or as...

  19. 78 FR 5421 - Proposed Information Collection; Comment Request; NOAA's Teacher at Sea Program

    Science.gov (United States)

    2013-01-25

    ... solicits information from interested educators: basic personal information, teaching experience and ideas... Services Questionnaire required of anyone selected to participate in the program. Once educators are... complete a Health Services Questionnaire, 15 minutes to deliver and discuss recommendation forms to persons...

  20. 75 FR 338 - Proposed Information Collection; Comment Request; NOAA Teacher at Sea Program

    Science.gov (United States)

    2010-01-05

    ... information from interested educators: basic personal information, teaching experience and ideas for applying program experience in their classrooms, plus two recommendations and a NOAA Health Services Questionnaire... minutes to complete a Health Services Questionnaire, 15 minutes to deliver and discuss recommendation...

  1. 77 FR 66951 - Proposed Information Collection; Comment Request; BIS Program Evaluation

    Science.gov (United States)

    2012-11-08

    ... feedback from seminar participants. This information helps BIS determine the effectiveness of its programs... collection). Affected Public: Business or other for-profit organizations. Estimated Number of Respondents: 3... Total Annual Cost to Public: $0. IV. Request for Comments Comments are invited on: (a) Whether the...

  2. 78 FR 48417 - Proposed Information Collection; Comment Request; Educational Partnership Program (EPP), Ernest F...

    Science.gov (United States)

    2013-08-08

    ... alumni student data collection are the Dr. Nancy Foster Scholarship Program and the Recruiting, Training.... Method of Collection Electronic applications and electronic forms are required from participants, and the primary methods of submittal are email and Internet transmission of electronic forms. Approximately 1% of...

  3. Relationship of tightly bound ADP and ATP to control and catalysis by chloroplast ATP synthase

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, J.; Xue, Z.; Du, Z.; Melese, T.; Boyer, P.D.

    1988-07-12

    Whether the tightly bound ADP that can cause a pronounced inhibition of ATP hydrolysis by the chloroplast ATP synthase and F/sub 1/ ATPase (CF/sub 1/) is bound at catalytic sites or at noncatalytic regulatory sites or both has been uncertain. The authors have used photolabeling by 2-azido-ATP and 2-azido-ADP to ascertain the location, with Mg/sup 2 +/ activation, of tightly bound ADP (a) that inhibits the hydrolysis of ATP by chloroplast ATP synthase, (b) that can result in an inhibited form of CF/sub 1/ that slowly regains activity during ATP hydrolysis, and (c) that arises when low concentrations of ADP markedly inhibit the hydrolysis of GTP by CF/sub 1/. The data show that in all instances the inhibition is associated with ADP binding without inorganic phosphate (P/sub i/) at catalytic sites. After photophosphorylation of ADP or 2-azido-ADP with (/sup 32/P)P/sub i/, similar amounts of the corresponding triphosphates are present on washed thylakoid membranes. Trials with appropriately labeled substrates show that a small portion of the tightly bound 2-azido-ATP gives rise to covalent labeling with an ATP moiety at noncatalytic sites but that most of the bound 2-azido-ATP gives rise to covalent labeling with an ATP moiety at noncatalytic sites but that most of the bound 2-azido-ATP gives rise to covalent labeling by an ADP moiety at a catalytic site. They also report the occurrence of a 1-2-min delay in the onset of the Mg/sup 2 +/-induced inhibition after addition of CF/sub 1/ to solutions containing Mg/sup 2 +/ and ATP, and that this delay is not associated with the filling of noncatalytic sites. A rapid burst of P/sub i/ formation is followed by a much lower, constant steady-state rate. The burst is not observed with GTP as a substrate or with Ca/sup 2 +/ as the activating cation.

  4. Molecular Events Involved in a Single Cycle of Ligand Transfer from an ATP Binding Cassette Transporter, LolCDE, to a Molecular Chaperone, LolA*

    OpenAIRE

    Taniguchi, Naohiro; Tokuda, Hajime

    2008-01-01

    An ATP binding cassette transporter LolCDE complex releases lipoproteins from the inner membrane of Escherichia coli in an ATP-dependent manner, leading to the formation of a complex between a lipoprotein and a periplasmic chaperone, LolA. LolA is proposed to undergo a conformational change upon the lipoprotein binding. The lipoprotein is then transferred from the LolA-lipoprotein complex to the outer membrane via LolB. Unlike most ATP binding cassette transporters med...

  5. Methodological proposal to tackle the Visual Basic program in senior high schools of Pinar del Rio. (First part

    Directory of Open Access Journals (Sweden)

    Manuel Pereira Rosa

    2003-06-01

    Full Text Available A proposed dosage for the contents to be addressed in the teaching of traditional programming languages in the pre-university level, methodological for treatment suggestions as well as a system of exercises in correspondence with the changes that take is offered in this article out at school, which may constitute material support for the planning, execution and control of the teaching process in this subject.

  6. Bioluminometric assay of ATP in mouse brain

    Indian Academy of Sciences (India)

    Firefly luciferase bioluminescence (FLB) is a highly sensitive and specific method for the analysis of adenosine-5-triphosphate (ATP) in biological samples. Earlier attempts to modify the FLB test for enhanced sensitivity have been typically based on in vitro cell systems. This study reports an optimized FLB procedure for the ...

  7. ORGANIZATION AND PLANNING IN CHILDREN WITH ADHD: EVALUATION AND PROPOSAL OF A STIMULATION PROGRAM

    Directory of Open Access Journals (Sweden)

    Josefina Rubiales

    2011-12-01

    Full Text Available The Attention Deficit Hyperactivity Disorder (ADHD is a neurobiological disorder of a complex and heterogeneous origin characterized by a persistent pattern of inattention, hyperactivity and / or impulsivity. Is one of the most common neurobehavioral disorders in childhood and adolescence, and one of the main reasons for consultation because of difficulties in school performance, behavior problems, difficulties of living at home and with peers, involvement in self-esteem and aggressiveness. The primary deficit is associated with executive dysfunction, among which is the organization and planning. The aim of this study was to compare the performance in organization and planning of children with and without a diagnosis of ADHD and submit a stimulation proposal according to their needs. MATERIALS AND METHODS: The clinical sample comprised 16 children diagnosed with ADHD and the control sample of 32 children without a diagnosis, in both cases 8 to 14 years old and from the city of Mar del Plata (Argentina. The instruments used to evaluate the organization and planning has been the subtest Torres of Mexico Child Neuropsychological Battery (ENI, and cubes subtests Construction, Completion and Management Object Test Story Weschler Intelligence for children and adolescents. The proposed treatment includes 8 sessions of stimulation. RESULTS AND CONCLUSIONS: Children with ADHD have greater difficulty in planning and organizational skills than the children of the control sample, from which it establishes a estimulation proposal, whose originality and advantage is accentuated in the ecological validity the process.

  8. Lyndon B. Johnson Space Center (JSC) proposed dual-use technology investment program in intelligent robots

    Science.gov (United States)

    Erikson, Jon D.

    1994-01-01

    This paper presents an overview of the proposed Lyndon B. Johnson Space Center (JSC) precompetitive, dual-use technology investment project in robotics. New robotic technology in advanced robots, which can recognize and respond to their environments and to spoken human supervision so as to perform a variety of combined mobility and manipulation tasks in various sectors, is an obejective of this work. In the U.S. economy, such robots offer the benefits of improved global competitiveness in a critical industrial sector; improved productivity by the end users of these robots; a growing robotics industry that produces jobs and profits; lower cost health care delivery with quality improvements; and, as these 'intelligent' robots become acceptable throughout society, an increase in the standard of living for everyone. In space, such robots will provide improved safety, reliability, and productivity as Space Station evolves, and will enable human space exploration (by human/robot teams). The proposed effort consists of partnerships between manufacturers, universities, and JSC to develop working production prototypes of these robots by leveraging current development by both sides. Currently targeted applications are in the manufacturing, health care, services, and construction sectors of the U.S. economy and in the inspection, servicing, maintenance, and repair aspects of space exploration. But the focus is on the generic software architecture and standardized interfaces for custom modules tailored for the various applications allowing end users to customize a robot as PC users customize PC's. Production prototypes would be completed in 5 years under this proposal.

  9. Proposed framework for the Western Area Power Administration Environmental Risk Management Program

    Energy Technology Data Exchange (ETDEWEB)

    Glantz, C.S.; DiMassa, F.V.; Pelto, P.J.; Brothers, A.J. [Pacific Northwest Lab., Richland, WA (United States); Roybal, A.L. [Western Area Power Administration, Golden, CO (United States)

    1994-12-01

    The Western Area Power Administration (Western) views environmental protection and compliance as a top priority as it manages the construction, operation, and maintenance of its vast network of transmission lines, substations, and other facilities. A recent Department of Energy audit of Western`s environmental management activities recommends that Western adopt a formal environmental risk program. To accomplish this goal, Western, in conjunction with Pacific Northwest Laboratory, is in the process of developing a centrally coordinated environmental risk program. This report presents the results of this design effort, and indicates the direction in which Western`s environmental risk program is heading. Western`s environmental risk program will consist of three main components: risk communication, risk assessment, and risk management/decision making. Risk communication is defined as an exchange of information on the potential for threats to human health, public safety, or the environment. This information exchange provides a mechanism for public involvement, and also for the participation in the risk assessment and management process by diverse groups or offices within Western. The objective of risk assessment is to evaluate and rank the relative magnitude of risks associated with specific environmental issues that are facing Western. The evaluation and ranking is based on the best available scientific information and judgment and serves as input to the risk management process. Risk management takes risk information and combines it with relevant non-risk factors (e.g., legal mandates, public opinion, costs) to generate risk management options. A risk management tool, such as decision analysis, can be used to help make risk management choices.

  10. EPA [Environmental Protection Agency] SITE [Superfund Innovative Technology Evaluation] program seeks technology proposals

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    EPA will issue an RFP to initiate the SITE-005 solicitation for demonstration of technologies under the Superfund Innovative Technology Evaluation (SITE) Program. This portion of the SITE program offers a mechanism for conducting a joint technology demonstration between EPA and the private sector. The goal of the demonstration program is to provide an opportunity for developers to demonstrate the performance of their technologies on actual hazardous wastes at Superfund sites, and to provide accurate and reliable data on that performance. Technologies selected must be of commercial scale and provide solutions to problems encountered at Superfund Sites. Primary emphasis in the RFP is on technologies that address: treatment of mixed, low level radioactive wastes in soils and groundwater; treatment of soils and sludges contaminated with organics and/or inorganics, materials handling as a preliminary step to treatment or further processing, treatment trains designed to handle specific wastes, are in situ technologies, especially those processes providing alternatives to conventional groundwater pump and treat techniques

  11. PROPOSAL FOR NEURAL-LINGUISTIC PROGRAMMING (N.L.P. INTHE ADMINISTRATIVE DEVELOPMENT OF LEADERSHIP SPORTS

    Directory of Open Access Journals (Sweden)

    Khalil Samira

    2010-08-01

    Full Text Available Neural-linguistic programming is an organised method to know the human self construction and dealing with it in fixed means and styles so as to decesisively affect the processes of perception, thinking, imaging, ideas,feeling and also in behavior, skills and the human body and mental performance (1 Neural-linguistic programming has a private nature because it is a group of mechanisms and practicaltechniques far from likeliness, so it enters in the circle of application and employment of the human abilities and possibilities. (9 Al Fiky (2001 points out that neural linguistic programming created the favourable environment to help individuals to get rid of their diseased fears and controlling in their negative reactions and thus improving communication with themselves and with others. He shows it took its way into the human life fields because itsways and strategies are used in the sectors of health, education, marketing and administration(2. The modern administration embarks on the human element that represents the most valuable elementsof administration and is the most effective on the productivity and with the increasing the effect of the human element in the efficacy of the administrative organizations, the need increased to consider the management of the human resources as an independent function of administrative functions that cancers the human element and onwhose efficiency, abilities, experience and zeal for work, the administration efficacy depends.

  12. MSR - SPHINX concept program Eros (Experimental zero power Salt reactor SR-0) - The proposed experimental program as a basis for validation of reactor physics methods

    Energy Technology Data Exchange (ETDEWEB)

    Hron, M.; Juricek, V.; Kyncl, J.; Mikisek, M.; Rypar, V. [Nuclear Research Institute Rez plc, Rez (Czech Republic)

    2007-07-01

    The Molten Salt Reactor (MSR) - SPHINX (SPent Hot fuel Incinerator by Neutron fluX) concept solves this principal problem of spent fuel treatment by means of so-called nuclear incineration. It means the burning of fissionable part of its inventory and transmutation of other problematic radionuclides by use of nuclear reactions with neutrons in a MSR-SPHINX system. This reactor system is an actinide burner (most in resonance neutron spectrum) and a radionuclide transmuter in a well-thermalized neutron spectrum. In the frame of the physical part, there are computational analyses and experimental activities. The experimental program has been focused, in its first stage, on a short-term irradiation of small size samples of molten-salt systems as well as structural materials proposed for the MSR blanket in the field of high neutron flux of research reactors. The proposed next stage of the program will focus on a large-scale experimental verification of design inputs by use of MSR-type inserting zones into the existing light water moderated experimental reactor LR-0, which may allow us to modify it into the experimental zero power salt reactor SR-0. There will be a detail description of the proposed program given in the paper together with the so far performed experiments and their first results. These realized experiments help us also to verify computational codes used, and to recognize some anomalies related to molten fluorides utilization. (authors)

  13. ATP-consuming and ATP-generating enzymes secreted by pancreas

    DEFF Research Database (Denmark)

    Yegutkin, Gennady G; Samburski, Sergei S; Jalkanen, Sirpa

    2006-01-01

    -generating enzymes in pancreatic juice, adenylate kinase, and NDP kinase, capable of sequentially phosphorylating AMP via ADP to ATP. Activities of nonspecific phosphatases, nucleotide pyrophosphatase/phosphodiesterases, and adenosine deaminase were negligible. Taken together, CCK-8 stimulation of pancreas causes...

  14. Medicare program; revision to accrual basis of accounting policy--HCFA. Proposed rule.

    Science.gov (United States)

    1998-05-18

    Current policy provides that payroll taxes a provider becomes obligated to remit to governmental agencies are included in allowable costs under Medicare only in the cost reporting period in which payment (upon which the payroll taxes are based) is actually made to an employee. Therefore, for payroll accrued in one year but not paid until the next year, the associated payroll taxes on the payroll are not an allowable cost until the next year. This proposed rule would make one exception, in the situation where payment would be made to the employee in the current year but for the fact the regularly scheduled payment date is after the end of the year. In that case, the rule would require allowance in the current year of accrued taxes on payroll that is accrued through the end of the year but not paid until the beginning of the next year, thus allowing accrued taxes on end-of-the year payroll in the same year that the accrual of the payroll itself is allowed. The effect of this proposal is not on the allowability of cost but rather only on the timing of payment; that is, the cost of payroll taxes on and-of-the-year payroll would be allowable in the current period rather than in the following period.

  15. Carbon and energy metabolism of atp mutants of Escherichia coli

    DEFF Research Database (Denmark)

    Jensen, Peter Ruhdal; Michelsen, Ole

    1992-01-01

    strain is not able to utilize the resulting proton motive force for ATP synthesis. Indeed, the ratio of ATP concentration to ADP concentration was decreased from 19 in the wild type to 7 in the atp mutant, and the membrane potential of the atp deletion strain was increased by 20%, confirming......The membrane-bound H+-ATPase plays a key role in free-energy transduction of biological systems. We report how the carbon and energy metabolism of Escherichia coli changes in response to deletion of the atp operon that encodes this enzyme. Compared with the isogenic wild-type strain, the growth...... rate and growth yield were decreased less than expected for a shift from oxidative phosphorylation to glycolysis alone as a source of ATP. Moreover, the respiration rate of a atp deletion strain was increased by 40% compared with the wild-type strain. This result is surprising, since the atp deletion...

  16. Identification of a lysosome membrane protein which could mediate ATP-dependent stable association of lysosomes to microtubules

    International Nuclear Information System (INIS)

    Mithieux, G.; Rousset, B.

    1989-01-01

    We have previously reported that purified thyroid lysosomes bind to reconstituted microtubules to form stable complexes, a process which is inhibited by ATP. Among detergent-solubilized lysosomal membrane protein, we identified a 50-kDa molecular component which binds to preassembled microtubules. The binding of this polypeptide to microtubules was decreased in the presence of ATP. We purified this 50-kDa protein by affinity chromatography on immobilized ATP. The 50-kDa protein bound to the ATP column was eluted by 1 mM ATP. The purified protein, labeled with 125I, exhibited the ability of interacting with microtubules. The binding process was inhibited by increasing concentrations of ATP, the half-maximal inhibitory effect being obtained at an ATP concentration of 0.35 mM. The interaction of the 50-kDa protein with microtubules is a saturable phenomenon since the binding of the 125I-labeled 50-kDa protein was inhibited by unlabeled solubilized lysosomal membrane protein containing the 50-kDa polypeptide but not by the same protein fraction from which the 50-kDa polypeptide had been removed by the ATP affinity chromatography procedure. The 50-kDa protein has the property to bind to pure tubulin coupled to an insoluble matrix. The 50-kDa protein was eluted from the tubulin affinity column by ATP. These findings support the conclusion that a protein inserted into the lysosomal membrane is able to bind directly to microtubules in a process which can be regulated by ATP. We propose that this protein could account for the association of lysosomes to microtubules demonstrated both in vitro and in intact cells

  17. A Training Program to Enhance Postgraduate Students' Research Skills in Preparing a Research Proposal in the Field of Curriculum and Instruction Methods of Arabic Language

    Science.gov (United States)

    Alfakih, Ahmed Hassan

    2017-01-01

    The study examined the impact of a training program on enhancing postgraduate students' research skills in preparing a research proposal. The nature of the skills required to prepare a research proposal were first determined using a questionnaire. A training program for improving such skills was then constructed and seven postgraduate students in…

  18. Highly Divergent Mitochondrial ATP Synthase Complexes in Tetrahymena thermophila

    NARCIS (Netherlands)

    Nina, Praveen Balabaskaran; Dudkina, Natalya V.; Kane, Lesley A.; van Eyk, Jennifer E.; Boekema, Egbert J.; Mather, Michael W.; Vaidya, Akhil B.; Eisen, Jonathan A.

    The F-type ATP synthase complex is a rotary nano-motor driven by proton motive force to synthesize ATP. Its F(1) sector catalyzes ATP synthesis, whereas the F(o) sector conducts the protons and provides a stator for the rotary action of the complex. Components of both F(1) and F(o) sectors are

  19. Cyclophilin D Promotes Brain Mitochondrial F1FO ATP Synthase Dysfunction in Aging Mice.

    Science.gov (United States)

    Gauba, Esha; Guo, Lan; Du, Heng

    2017-01-01

    Brain aging is the known strongest risk factor for Alzheimer's disease (AD). In recent years, mitochondrial deficits have been proposed to be a common mechanism linking brain aging to AD. Therefore, to elucidate the causative mechanisms of mitochondrial dysfunction in aging brains is of paramount importance for our understanding of the pathogenesis of AD, in particular its sporadic form. Cyclophilin D (CypD) is a specific mitochondrial protein. Recent studies have shown that F1FO ATP synthase oligomycin sensitivity conferring protein (OSCP) is a binding partner of CypD. The interaction of CypD with OSCP modulates F1FO ATP synthase function and mediates mitochondrial permeability transition pore (mPTP) opening. Here, we have found that increased CypD expression, enhanced CypD/OSCP interaction, and selective loss of OSCP are prominent brain mitochondrial changes in aging mice. Along with these changes, brain mitochondria from the aging mice demonstrated decreased F1FO ATP synthase activity and defective F1FO complex coupling. In contrast, CypD deficient mice exhibited substantially mitigated brain mitochondrial F1FO ATP synthase dysfunction with relatively preserved mitochondrial function during aging. Interestingly, the aging-related OSCP loss was also dramatically attenuated by CypD depletion. Therefore, the simplest interpretation of this study is that CypD promotes F1FO ATP synthase dysfunction and the resultant mitochondrial deficits in aging brains. In addition, in view of CypD and F1FO ATP synthase alterations seen in AD brains, the results further suggest that CypD-mediated F1FO ATP synthase deregulation is a shared mechanism linking mitochondrial deficits in brain aging and AD.

  20. Permeability transition in human mitochondria persists in the absence of peripheral stalk subunits of ATP synthase.

    Science.gov (United States)

    He, Jiuya; Carroll, Joe; Ding, Shujing; Fearnley, Ian M; Walker, John E

    2017-08-22

    The opening of a nonspecific channel, known as the permeability transition pore (PTP), in the inner membranes of mitochondria can be triggered by calcium ions, leading to swelling of the organelle, disruption of the inner membrane and ATP synthesis, and cell death. Pore opening can be inhibited by cyclosporin A mediated via cyclophilin D. It has been proposed that the pore is associated with the dimeric ATP synthase and the oligomycin sensitivity conferral protein (OSCP), a component of the enzyme's peripheral stalk, provides the site at which cyclophilin D interacts. Subunit b contributes a central α-helical structure to the peripheral stalk, extending from near the top of the enzyme's catalytic domain and crossing the membrane domain of the enzyme via two α-helices. We investigated the possible involvement of the subunit b and the OSCP in the PTP by generating clonal cells, HAP1-Δb and HAP1-ΔOSCP, lacking the membrane domain of subunit b or the OSCP, respectively, in which the corresponding genes, ATP5F1 and ATP5O , had been disrupted. Both cell lines preserve the characteristic properties of the PTP; therefore, the membrane domain of subunit b does not contribute to the PTP, and the OSCP does not provide the site of interaction with cyclophilin D. The membrane subunits ATP6, ATP8, and subunit c have been eliminated previously from possible participation in the PTP; thus, the only subunits of ATP synthase that could participate in pore formation are e, f, g, diabetes-associated protein in insulin-sensitive tissues (DAPIT), and the 6.8-kDa proteolipid.

  1. Cost-Benefit Comparison of Two Proposed Overseas Programs for Reducing Chronic Hepatitis B Infection among Refugees: Is Screening Essential?

    Science.gov (United States)

    Jazwa, Amelia; Coleman, Margaret S.; Gazmararian, Julie; Wingate, La’Marcus T.; Maskery, Brian; Mitchell, Tarissa; Weinberg, Michelle

    2015-01-01

    Background Refugees are at an increased risk of chronic Hepatitis B Virus (HBV) infection because many of their countries of origin, as well as host countries, have intermediate-to-high prevalence rates. Refugees arriving to the US are also at risk of serious sequelae from chronic HBV infection because they are not routinely screened for the virus overseas or in domestic post-arrival exams, and may live in the US for years without awareness of their infection status. Methods A cohort of 26,548 refugees who arrived in Minnesota and Georgia during 2005–2010 was evaluated to determine the prevalence of chronic HBV infection. This prevalence information was then used in a cost-benefit analysis comparing two variations of a proposed overseas program to prevent or ameliorate the effects of HBV infection, titled ‘Screen, then vaccinate or initiate management’ (SVIM) and ‘Vaccinate only’ (VO). The analyses were performed in 2013. All values were converted to US 2012 dollars. Results The estimated six year period-prevalence of chronic HBV infection was 6.8% in the overall refugee population arriving to Minnesota and Georgia and 7.1% in those ≥ 6 years of age. The SVIM program variation was more cost beneficial than VO. While the up-front costs of SVIM were higher than VO ($154,084 vs. $73,758; n=58,538 refugees), the SVIM proposal displayed a positive net benefit, ranging from $24 million to $130 million after only 5 years since program initiation, depending on domestic post-arrival screening rates in the VO proposal. Conclusions Chronic HBV infection remains an important health problem in refugees resettling to the United States. An overseas screening policy for chronic HBV infection is more cost-beneficial than a ‘Vaccination only’ policy. The major benefit drivers for the screening policy are earlier medical management of chronic HBV infection and averted lost societal contributions from premature death. PMID:25595868

  2. Cost-benefit comparison of two proposed overseas programs for reducing chronic Hepatitis B infection among refugees: is screening essential?

    Science.gov (United States)

    Jazwa, Amelia; Coleman, Margaret S; Gazmararian, Julie; Wingate, La'Marcus T; Maskery, Brian; Mitchell, Tarissa; Weinberg, Michelle

    2015-03-10

    Refugees are at an increased risk of chronic Hepatitis B virus (HBV) infection because many of their countries of origin, as well as host countries, have intermediate-to-high prevalence rates. Refugees arriving to the US are also at risk of serious sequelae from chronic HBV infection because they are not routinely screened for the virus overseas or in domestic post-arrival exams, and may live in the US for years without awareness of their infection status. A cohort of 26,548 refugees who arrived in Minnesota and Georgia during 2005-2010 was evaluated to determine the prevalence of chronic HBV infection. This prevalence information was then used in a cost-benefit analysis comparing two variations of a proposed overseas program to prevent or ameliorate the effects of HBV infection, titled 'Screen, then vaccinate or initiate management' (SVIM) and 'Vaccinate only' (VO). The analyses were performed in 2013. All values were converted to US 2012 dollars. The estimated six year period-prevalence of chronic HBV infection was 6.8% in the overall refugee population arriving to Minnesota and Georgia and 7.1% in those ≥6 years of age. The SVIM program variation was more cost beneficial than VO. While the up-front costs of SVIM were higher than VO ($154,084 vs. $73,758; n=58,538 refugees), the SVIM proposal displayed a positive net benefit, ranging from $24 million to $130 million after only 5 years since program initiation, depending on domestic post-arrival screening rates in the VO proposal. Chronic HBV infection remains an important health problem in refugees resettling to the United States. An overseas screening policy for chronic HBV infection is more cost-beneficial than a 'Vaccination only' policy. The major benefit drivers for the screening policy are earlier medical management of chronic HBV infection and averted lost societal contributions from premature death. Published by Elsevier Ltd.

  3. Guidelines for a Comprehensive Care Program to Ostomized Patients and Families: a Nursing proposal

    Directory of Open Access Journals (Sweden)

    Paula Alvarenga de Figueiredo

    2016-01-01

    Full Text Available Objectives: describe care needs and demands that mark the discursive practices of ostomized clients and family members and discuss guidelines for a comprehensive care program to ostomized clients and their families, organized by macrosociological categories. Method: Creative and Sensitive, involving 17 ostomized subjects and family members at a municipal outpatient clinic. The ethical aspects were complied with. A characterization form was used, as well as Creativity and Sensitivity Dynamics: "speaking map", "body-knowledge" and "calendar". Critical Discourse Analysis was applied. Results: the health needs and care demands of the ostomized patients and their family members, in their multiple dimensions, were constituted in the home and community, outpatient and social context, implying new orientations for nursing care. The unveiling of the data brought elements that constituted guidelines, in a macrosociological approach, to achieve the expanded integrality of nursing care. Conclusion: the ostomized clients are unique in their genre/peculiar from Latin sui generis, calling for strategies that respond to and distinguish their specificities. Elaborating a Public Health Policy that improves and reorganizes the care demands, taking into account these individual biopsychosocial and spiritual aspects, is a possible and irrevocable target in the attempt to achieve better conditions of health and wellbeing.

  4. H+/ATP ratio during ATP hydrolysis by mitochondria: modification of the chemiosmotic theory.

    Science.gov (United States)

    Brand, M D; Lehninger, A L

    1977-01-01

    The stoichiometry of H+ ejection by mitochondria during hydrolysis of a small pulse of ATP (the H+/ATP ratio) has been reexamined in the light of our recent observation that the stoichiometry of H+ ejection during mitochondrial electron transport (the H+/site ratio) was previously underestimated. We show that earlier estimates of the H+/ATP ratio in intact mitochondria were based upon an invalid correction for scaler H+ production and describe a modified method for determination of this ratio which utilizes mersalyl or N-ethylmaleimide to prevent complicating transmembrane movements of phosphate and H+. This method gives a value for the H+/ATP ratio of 2.0 without the need for questionable corrections, compared with a value of 3.0 for the H+/site ratio also obtained by pulse methods. A modified version of the chemiosmotic theory is presented, in which 3 H+ are ejected per pair of electrons traversing each energy-conserving site of the respiratory chain. Of these, 2 H+ return to the matrix through the ATPase to form ATP from ADP and phosphate, and 1 H+ returns through the combined action of the phosphate and adenine nucleotide exchange carriers of the inner membrane to allow the energy-requiring influx of Pi and ADP3- and efflux of ATP4-. Thus, up to one-third of the energy input into synthesis of extramitochondrial ATP may be required for transport work. Since other methods suggest that the H+/site significantly exceeds 3.0, an alternative possibility is that 4 h+ are ejected per site, followed by return of 3 H+ through the ATPase and 1 H+ through the operation of the proton-coupled membrane transport systems. PMID:17116

  5. Proposed training program for construction personnel involved in remedial action work at sites contaminated by naturally occurring radionuclides

    International Nuclear Information System (INIS)

    Berven, B.A.; Goldsmith, W.A.; Haywood, F.F.; Schiager, K.J.

    1979-01-01

    Many sites used during the early days of the US atomic energy program are contaminated with radionuclides of the primordial decay chains (uranium, thorium, and actinium series). This contamination consists of residues resulting from refining and processing uranium and thorium. Preparation of these sites for release to unrestricted private use will involve the assistance of construction workers, many of whom have limited knowledge of the hazards associated with radioactive materials. Therefore, there is a need to educate these workers in the fundamentals of radioactive material handling to minimize exposures and possible spread of contamination. This training should disseminate relevant information at an appropriate educational level and should instill a cautious, common-sense attitude toward the handling of radioactive materials. The training should emphasize basic information concerning environmental radiation within a context of relative risk. A multi-media format, including colorful visual aids, demonstration, and discussion, should be used to maximize motivation and retention. A detailed, proposed training program design is presented

  6. A Proposal for a Three Detector Short-Baseline Neutrino Oscillation Program in the Fermilab Booster Neutrino Beam

    CERN Document Server

    Antonello, M.; Bellini, V.; Benetti, P.; Bertolucci, S.; Bilokon, H.; Boffelli, F.; Bonesini, M.; Bremer, J.; Calligarich, E.; Centro, S.; Cocco, A.G.; Dermenev, A.; Falcone, A.; Farnese, C.; Fava, A.; Ferrari, A.; Gibin, D.; Gninenko, S.; Golubev, N.; Guglielmi, A.; Ivashkin, A.; Kirsanov, M.; Kisiel, J.; Kose, U.; Mammoliti, F.; Mannocchi, G.; Menegolli, A.; Meng, G.; Mladenov, D.; Montanari, C.; Nessi, M.; Nicoletto, M.; Noto, F.; Picchi, P.; Pietropaolo, F.; Plonski, P.; Potenza, R.; Rappoldi, A.; Raselli, G.L.; Rossella, M.; Rubbia, C.; Sala, P.; Scaramelli, A.; Sobczyk, J.; Spanu, M.; Stefan, D.; Sulej, R.; Sutera, C.M.; Torti, M.; Tortorici, F.; Varanini, F.; Ventura, S.; Vignoli, C.; Wachala, T.; Zani, A.; Adams, C.; Andreopoulos, C.; Ankowski, A.M.; Asaadi, J.; Bagby, L.; Baller, B.; Barros, N.; Bass, M.; Bishai, M.; Bitadze, A.; Bugel, L.; Camilleri, L.; Cavanna, F.; Chen, H.; Chi, C.; Church, E.; Cianci, D.; Collin, G.H.; Conrad, J.M.; De Geronimo, G.; Dharmapalan, R.; Djurcic, Z.; Ereditato, A.; Esquivel, J.; Evans, J.; Fleming, B.T.; Foreman, W.M.; Freestone, J.; Gamble, T.; Garvey, G.; Genty, V.; Goldi, D.; Gramellini, E.; Greenlee, H.; Guenette, R.; Hackenburg, A.; Hanni, R.; Ho, J.; Howell, J.; James, C.; Jen, C.M.; Jones, B.J.P.; Kalousis, L.N.; Karagiorgi, G.; Ketchum, W.; Klein, J.; Klinger, J.; Kreslo, I.; Kudryavtsev, V.A.; Lissauer, D.; Livesly, P.; Louis, W.C.; Luthi, M.; Mariani, C.; Mavrokoridis, K.; McCauley, N.; McConkey, N.; Mercer, I.; Miao, T.; Mills, G.B.; Montanari, D.; Moon, J.; Moss, Z.; Mufson, S.; Norris, B.; Nowak, J.; Pal, S.; Palamara, O.; Pater, J.; Pavlovic, Z.; Perkin, J.; Pulliam, G.; Qian, X.; Qiuguang, L.; Radeka, V.; Rameika, R.; Ratoff, P.N.; Richardson, M.; von Rohr, C.Rudolf; Russell, B.; Schmitz, D.W.; Shaevitz, M.H.; Sippach, B.; Soderberg, M.; Soldner-Rembold, S.; Spitz, J.; Spooner, N.; Strauss, T.; Szelc, A.M.; Taylor, C.E.; Terao, K.; Thiesse, M.; Thompson, L.; Thomson, M.; Thorn, C.; Toups, M.; Touramanis, C.; Van de Water, R.G.; Weber, M.; Whittington, D.; Wongjirad, T.; Yu, B.; Zeller, G.P.; Zennamo, J.; Acciarri, R.; An, R.; Barr, G.; Blake, A.; Bolton, T.; Bromberg, C.; Caratelli, D.; Carls, B.; Convery, M.; Dytmam, S.; Eberly, B.; Gollapinni, S.; Graham, M.; Grosso, R.; Hen, O.; Hewes, J.; Horton-Smith, G.; Johnson, R.A.; Joshi, J.; Jostlein, H.; Kaleko, D.; Kirby, B.; Kirby, M.; Kobilarcik, T.; Li, Y.; Littlejohn, B.; Lockwitz, S.; Lundberg, B.; Marchionni, A.; Marshall, J.; McDonald, K.; Meddage, V.; Miceli, T.; Mooney, M.; Moulai, M.H.; Murrells, R.; Naples, D.; Nienaber, P.; Paolone, V.; Papavassiliou, V.; Pate, S.; Pordes, S.; Raaf, J.L.; Rebel, B.; Rochester, L.; Schukraft, A.; Seligman, W.; St. John, J.; Tagg, N.; Tsai, Y.; Usher, T.; Wolbers, S.; Woodruff, K.; Xu, M.; Yang, T.; Zhang, C.; Badgett, W.; Biery, K.; Brice, S.J.; Dixon, S.; Geynisman, M.; Moore, C.; Snider, E.; Wilson, P.

    2015-01-01

    A Short-Baseline Neutrino (SBN) physics program of three LAr-TPC detectors located along the Booster Neutrino Beam (BNB) at Fermilab is presented. This new SBN Program will deliver a rich and compelling physics opportunity, including the ability to resolve a class of experimental anomalies in neutrino physics and to perform the most sensitive search to date for sterile neutrinos at the eV mass-scale through both appearance and disappearance oscillation channels. Using data sets of 6.6e20 protons on target (P.O.T.) in the LAr1-ND and ICARUS T600 detectors plus 13.2e20 P.O.T. in the MicroBooNE detector, we estimate that a search for muon neutrino to electron neutrino appearance can be performed with ~5 sigma sensitivity for the LSND allowed (99% C.L.) parameter region. In this proposal for the SBN Program, we describe the physics analysis, the conceptual design of the LAr1-ND detector, the design and refurbishment of the T600 detector, the necessary infrastructure required to execute the program, and a possible...

  7. Optimality principle for the coupled chemical reactions of ATP synthesis and its molecular interpretation

    Science.gov (United States)

    Nath, Sunil

    2018-05-01

    Metabolic energy obtained from the coupled chemical reactions of oxidative phosphorylation (OX PHOS) is harnessed in the form of ATP by cells. We experimentally measured thermodynamic forces and fluxes during ATP synthesis, and calculated the thermodynamic efficiency, η and the rate of free energy dissipation, Φ. We show that the OX PHOS system is tuned such that the coupled nonequilibrium processes operate at optimal η. This state does not coincide with the state of minimum Φ but is compatible with maximum Φ under the imposed constraints. Conditions that must hold for species concentration in order to satisfy the principle of optimal efficiency are derived analytically and a molecular explanation based on Nath's torsional mechanism of energy transduction and ATP synthesis is suggested. Differences of the proposed principle with Prigogine's principle are discussed.

  8. Yeast Mitochondrial Interactosome Model: Metabolon Membrane Proteins Complex Involved in the Channeling of ADP/ATP

    Directory of Open Access Journals (Sweden)

    Benjamin Clémençon

    2012-02-01

    Full Text Available The existence of a mitochondrial interactosome (MI has been currently well established in mammalian cells but the exact composition of this super-complex is not precisely known, and its organization seems to be different from that in yeast. One major difference is the absence of mitochondrial creatine kinase (MtCK in yeast, unlike that described in the organization model of MI, especially in cardiac, skeletal muscle and brain cells. The aim of this review is to provide a detailed description of different partner proteins involved in the synergistic ADP/ATP transport across the mitochondrial membranes in the yeast Saccharomyces cerevisiae and to propose a new mitochondrial interactosome model. The ADP/ATP (Aacp and inorganic phosphate (PiC carriers as well as the VDAC (or mitochondrial porin catalyze the import and export of ADP, ATP and Pi across the mitochondrial membranes. Aacp and PiC, which appear to be associated with the ATP synthase, consist of two nanomotors (F0, F1 under specific conditions and form ATP synthasome. Identification and characterization of such a complex were described for the first time by Pedersen and co-workers in 2003.

  9. NCEP-ATP III and IDF criteria for metabolic syndrome predict type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Eva Sulistiowati

    2016-05-01

    Full Text Available Background Subjects with metabolic syndrome (MetS have a greater risk for acquiring type 2 diabetes mellitus (type 2 DM. The MetS criteria usually used are those of the National Cholesterol Education Program Expert Panel (NCEP and Adult Treatment Panel III (ATP III and of the International Diabetes Federation (IDF. This study aimed to evaluate the modified NCEP-ATP III and IDF criteria as predictor of type 2 DM among subjects with MetS.   Methods A cohort study was conducted among 4240 subjects with MetS. MetS was determined according to the modified NCEP-ATP III and IDF criteria. The study followed up 3324 non-diabetic subjects of the cohort study of non-communicable disease (NCD risk factors (NCD study during a 2-year period. Type 2 DM was determined from the diagnosis by health personnel or from fasting blood glucose of ≥126 mg/dL or blood glucose of ≥200 mg/dL, 2 hours after 75g glucose loading.   Results The MetS prevalence based on modified NCEP ATP III and IDF criteria in non-DM subjects was 17.1% and 15.6%, respectively. The risk for DM in subjects with MetS using modified NCEP ATP III and IDF criteria was 4.7 (CI 95%: 3.4-6.5 and 4.1 (CI 95%: 3.0-5.7, respectively.   Conclusions Both MetS criteria can be used as predictors of the occurrence of DM type 2, but the modified NCEP-ATP III is more properly applied than the IDF criteria in subjects with MetS. Screening programs and routine monitoring of MetS components are required for early detection of type 2 DM.

  10. H Scan/AHP decision process planning for evaluating and ranking of proposals submitted to the DOE hydrogen program

    Energy Technology Data Exchange (ETDEWEB)

    Szoka de Valladares, M.R. [National Renwable Energy Lab., Washington, DC (United States); Mack, S. [Energtics, Washington, DC (United States)

    1995-09-01

    The DOE Hydrogen Program needs to develop criteria as part of a systematic evaluation process for proposal identification, evaluation and selection. The H Scan component of this process provides a framework in which a project proposer can fully describe their candidate technology system and its components. The H Scan complements traditional methods of capturing cost and technical information. It consists of a special set of survey forms designed to elicit information so expert reviewers can assess the proposal relative to DOE specified selection criteria. The Analytic Hierarchy Process (AHP) component of the decision process assembles the management defined evaluation and selection criteria into a coherent multi-level decision construct by which projects can be evaluated in pair-wise comparisons. The AHP model will reflect management`s objectives and it will assist in the ranking of individual projects based on the extent to which each contributes to management`s objectives. This paper contains a detailed description of the products and activities associated with the planning and evaluation process: The objectives or criteria; the H Scan; and The Analytic Hierarchy Process (AHP).

  11. Proposing a New Approach for Supplier Selection Based on Kraljic’s Model Using FMEA and Integer Linear Programming

    Directory of Open Access Journals (Sweden)

    S. Mohammad Arabzad

    2012-06-01

    Full Text Available In recent years, numerous methods have been proposed to deal with supplier evaluation and selection problem, but a point which has been usually neglected by researchers is the role of purchasing items. The aim of this paper is to propose an integrated approach to select suppliers and allocate orders on the basis of the nature of the purchasing items which means that this issue plays an important role in supplier selection and order allocation. Therefore, items are first categorized according to the Kraljic’s model by the use of FMEA technique. Then, suppliers are categorized and evaluated in four phases with respect to different types of purchasing items (Strategic, Bottleneck, Leverage and Routine. Finally, an integer linear programming is utilized to allocate purchasing orders to suppliers. Furthermore, an empirical example is conducted to illustrate the stage of proposed approach. Results imply that ranking of suppliers and allocation of purchasing items based on the nature of purchasing items will create more capabilities in managing purchasing items and suppliers .

  12. Red blood cell dynamics: from cell deformation to ATP release.

    Science.gov (United States)

    Wan, Jiandi; Forsyth, Alison M; Stone, Howard A

    2011-10-01

    The mechanisms of red blood cell (RBC) deformation under both static and dynamic, i.e., flow, conditions have been studied extensively since the mid 1960s. Deformation-induced biochemical reactions and possible signaling in RBCs, however, were proposed only fifteen years ago. Therefore, the fundamental relationship between RBC deformation and cellular signaling dynamics i.e., mechanotransduction, remains incompletely understood. Quantitative understanding of the mechanotransductive pathways in RBCs requires integrative studies of physical models of RBC deformation and cellular biochemical reactions. In this article we review the physical models of RBC deformation, spanning from continuum membrane mechanics to cellular skeleton dynamics under both static and flow conditions, and elaborate the mechanistic links involved in deformation-induced ATP release. This journal is © The Royal Society of Chemistry 2011

  13. Bioanalytical Applications of Real-Time ATP Imaging Via Bioluminescence

    Energy Technology Data Exchange (ETDEWEB)

    Gruenhagen, Jason Alan [Iowa State Univ., Ames, IA (United States)

    2003-01-01

    The research discussed within involves the development of novel applications of real-time imaging of adenosine 5'-triphosphate (ATP). ATP was detected via bioluminescence and the firefly luciferase-catalyzed reaction of ATP and luciferin. The use of a microscope and an imaging detector allowed for spatially resolved quantitation of ATP release. Employing this method, applications in both biological and chemical systems were developed. First, the mechanism by which the compound 48/80 induces release of ATP from human umbilical vein endothelial cells (HUVECs) was investigated. Numerous enzyme activators and inhibitors were utilized to probe the second messenger systems involved in release. Compound 48/80 activated a G{sub q}-type protein to initiate ATP release from HUVECs. Ca2+ imaging along with ATP imaging revealed that activation of phospholipase C and induction of intracellular Ca2+ signaling were necessary for release of ATP. Furthermore, activation of protein kinase C inhibited the activity of phospholipase C and thus decreased the magnitude of ATP release. This novel release mechanism was compared to the existing theories of extracellular release of ATP. Bioluminescence imaging was also employed to examine the role of ATP in the field of neuroscience. The central nervous system (CNS) was dissected from the freshwater snail Lymnaea stagnalis. Electrophysiological experiments demonstrated that the neurons of the Lymnaea were not damaged by any of the components of the imaging solution. ATP was continuously released by the ganglia of the CNS for over eight hours and varied from ganglion to ganglion and within individual ganglia. Addition of the neurotransmitters K+ and serotonin increased release of ATP in certain regions of the Lymnaea CNS. Finally, the ATP imaging technique was investigated for the study of drug release systems. MCM-41-type mesoporous nanospheres were loaded with ATP and end-capped with mercaptoethanol

  14. Electron transfer precedes ATP hydrolysis during nitrogenase catalysis

    Science.gov (United States)

    Duval, Simon; Danyal, Karamatullah; Shaw, Sudipta; Lytle, Anna K.; Dean, Dennis R.; Hoffman, Brian M.; Antony, Edwin; Seefeldt, Lance C.

    2013-01-01

    The biological reduction of N2 to NH3 catalyzed by Mo-dependent nitrogenase requires at least eight rounds of a complex cycle of events associated with ATP-driven electron transfer (ET) from the Fe protein to the catalytic MoFe protein, with each ET coupled to the hydrolysis of two ATP molecules. Although steps within this cycle have been studied for decades, the nature of the coupling between ATP hydrolysis and ET, in particular the order of ET and ATP hydrolysis, has been elusive. Here, we have measured first-order rate constants for each key step in the reaction sequence, including direct measurement of the ATP hydrolysis rate constant: kATP = 70 s−1, 25 °C. Comparison of the rate constants establishes that the reaction sequence involves four sequential steps: (i) conformationally gated ET (kET = 140 s−1, 25 °C), (ii) ATP hydrolysis (kATP = 70 s−1, 25 °C), (iii) Phosphate release (kPi = 16 s−1, 25 °C), and (iv) Fe protein dissociation from the MoFe protein (kdiss = 6 s−1, 25 °C). These findings allow completion of the thermodynamic cycle undergone by the Fe protein, showing that the energy of ATP binding and protein–protein association drive ET, with subsequent ATP hydrolysis and Pi release causing dissociation of the complex between the Feox(ADP)2 protein and the reduced MoFe protein. PMID:24062462

  15. Electron transfer precedes ATP hydrolysis during nitrogenase catalysis.

    Science.gov (United States)

    Duval, Simon; Danyal, Karamatullah; Shaw, Sudipta; Lytle, Anna K; Dean, Dennis R; Hoffman, Brian M; Antony, Edwin; Seefeldt, Lance C

    2013-10-08

    The biological reduction of N2 to NH3 catalyzed by Mo-dependent nitrogenase requires at least eight rounds of a complex cycle of events associated with ATP-driven electron transfer (ET) from the Fe protein to the catalytic MoFe protein, with each ET coupled to the hydrolysis of two ATP molecules. Although steps within this cycle have been studied for decades, the nature of the coupling between ATP hydrolysis and ET, in particular the order of ET and ATP hydrolysis, has been elusive. Here, we have measured first-order rate constants for each key step in the reaction sequence, including direct measurement of the ATP hydrolysis rate constant: kATP = 70 s(-1), 25 °C. Comparison of the rate constants establishes that the reaction sequence involves four sequential steps: (i) conformationally gated ET (kET = 140 s(-1), 25 °C), (ii) ATP hydrolysis (kATP = 70 s(-1), 25 °C), (iii) Phosphate release (kPi = 16 s(-1), 25 °C), and (iv) Fe protein dissociation from the MoFe protein (kdiss = 6 s(-1), 25 °C). These findings allow completion of the thermodynamic cycle undergone by the Fe protein, showing that the energy of ATP binding and protein-protein association drive ET, with subsequent ATP hydrolysis and Pi release causing dissociation of the complex between the Fe(ox)(ADP)2 protein and the reduced MoFe protein.

  16. A taste for ATP: neurotransmission in taste buds

    Science.gov (United States)

    Kinnamon, Sue C.; Finger, Thomas E.

    2013-01-01

    Not only is ATP a ubiquitous source of energy but it is also used widely as an intercellular signal. For example, keratinocytes release ATP in response to numerous external stimuli including pressure, heat, and chemical insult. The released ATP activates purinergic receptors on nerve fibers to generate nociceptive signals. The importance of an ATP signal in epithelial-to-neuronal signaling is nowhere more evident than in the taste system. The receptor cells of taste buds release ATP in response to appropriate stimulation by tastants and the released ATP then activates P2X2 and P2X3 receptors on the taste nerves. Genetic ablation of the relevant P2X receptors leaves an animal without the ability to taste any primary taste quality. Of interest is that release of ATP by taste receptor cells occurs in a non-vesicular fashion, apparently via gated membrane channels. Further, in keeping with the crucial role of ATP as a neurotransmitter in this system, a subset of taste cells expresses a specific ectoATPase, NTPDase2, necessary to clear extracellular ATP which otherwise will desensitize the P2X receptors on the taste nerves. The unique utilization of ATP as a key neurotransmitter in the taste system may reflect the epithelial rather than neuronal origins of the receptor cells. PMID:24385952

  17. A taste for ATP: neurotransmission in taste buds

    Directory of Open Access Journals (Sweden)

    Thomas E. Finger

    2013-12-01

    Full Text Available Not only is ATP a ubiquitous source of energy but it is also used widely as an intercellular signal. For example, keratinocytes release ATP in response to numerous external stimuli including pressure, heat and chemical insult. The released ATP activates purinergic receptors on nerve fibers to generate nociceptive signals. The importance of an ATP signal in epithelial-to-neuronal signaling is nowhere more evident than in the taste system. The receptor cells of taste buds release ATP in response to appropriate stimulation by tastants and the released ATP then activates P2X2 and P2X3 receptors on the taste nerves. Genetic ablation of the relevant P2X receptors leaves an animal without the ability to taste any primary taste quality. Of interest is that release of ATP by taste receptor cells occurs in a non-vesicular fashion, apparently via gated membrane channels. Further, in keeping with the crucial role of ATP as a neurotransmitter in this system, a subset of taste cells expresses a specific ectoATPase, NTPDase2, necessary to clear extracellular ATP which otherwise will desensitize the P2X receptors on the taste nerves. The unique utilization of ATP as a key neurotransmitter in the taste system may reflect the epithelial rather than neuronal origins of the receptor cells.

  18. Modeling steady state SO2-dependent changes in capillary ATP concentration using novel O2 micro-delivery methods

    Science.gov (United States)

    Ghonaim, Nour W.; Fraser, Graham M.; Ellis, Christopher G.; Yang, Jun; Goldman, Daniel

    2013-01-01

    Adenosine triphosphate (ATP) is known to be released from the erythrocyte in an oxygen (O2) dependent manner. Since ATP is a potent vasodilator, it is proposed to be a key regulator in the pathway that mediates micro-vascular response to varying tissue O2 demand. We propose that ATP signaling mainly originates in the capillaries due to the relatively long erythrocyte transit times in the capillary and the short ATP diffusion distance to the electrically coupled endothelium. We have developed a computational model to investigate the effect of delivering or removing O2 to limited areas at the surface of a tissue with an idealized parallel capillary array on total ATP concentration. Simulations were conducted when exposing full surface to perturbations in tissue O2 tension (PO2) or locally using a circular micro-outlet (~100 μm in diameter), a square micro-slit (200 × 200 μm), or a rectangular micro-slit (1000 μm wide × 200 μm long). Results indicated the rectangular micro-slit has the optimal dimensions for altering hemoglobin saturations (SO2) in sufficient number capillaries to generate effective changes in total [ATP]. This suggests a threshold for the minimum number of capillaries that need to be stimulated in vivo by imposed tissue hypoxia to induce a conducted micro-vascular response. SO2 and corresponding [ATP] changes were also modeled in a terminal arteriole (9 μm in diameter) that replaces 4 surface capillaries in the idealized network geometry. Based on the results, the contribution of terminal arterioles to the net change in [ATP] in the micro-vascular network is minimal although they would participate as O2 sources thus influencing the O2 distribution. The modeling data presented here provide important insights into designing a novel micro-delivery device for studying micro-vascular O2 regulation in the capillaries in vivo. PMID:24069001

  19. A sensitive electrochemical aptasensor for ATP detection based on exonuclease III-assisted signal amplification strategy.

    Science.gov (United States)

    Bao, Ting; Shu, Huawei; Wen, Wei; Zhang, Xiuhua; Wang, Shengfu

    2015-03-03

    A target-induced structure-switching electrochemical aptasensor for sensitive detection of ATP was successfully constructed which was based on exonuclease III-catalyzed target recycling for signal amplification. With the existence of ATP, methylene blue (MB) labeled hairpin DNA formed G-quadruplex with ATP, which led to conformational changes of the hairpin DNA and created catalytic cleavage sites for exonuclease III (Exo III). Then the structure-switching DNA hybridized with capture DNA which made MB close to electrode surface. Meanwhile, Exo III selectively digested aptamer from its 3'-end, thus G-quadruplex structure was destroyed and ATP was released for target recycling. The Exo III-assisted target recycling amplified electrochemical signal significantly. Fluorescence experiment was performed to confirm the structure-switching process of the hairpin DNA. In fluorescence experiment, AuNPs-aptamer conjugates were synthesized, AuNPs quenched fluorescence of MB, the target-induced structure-switching made Exo III digested aptamer, which restored fluorescence. Under optimized conditions, the proposed aptasensor showed a linear range of 0.1-20 nM with a detection limit of 34 pM. In addition, the proposed aptasensor had good stability and selectivity, offered promising choice for the detection of other small molecules. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Proposed Regulation of Fuels and Fuel Additives: Federal Volatility Control Program in the Denver-Boulder-Greeley-Ft. Collins-Loveland, Colorado, 1997 8-Hour Ozone Nonattainment Area

    Science.gov (United States)

    This notice proposes establishing an applicable standard of 7.8 pounds (psi) Reid vapor pressure under the federal volatility control program, in the Denver-Boulder-Greeley-Ft. Collins-Loveland, Colorado, 1997 8-hour ozone nonattainment area.

  1. Stoichiometry of vectorial H+ movements coupled to electron transport and to ATP synthesis in mitochondria

    Science.gov (United States)

    Alexandre, Adolfo; Reynafarje, Baltazar; Lehninger, Albert L.

    1978-01-01

    In order to verify more directly our earlier measurements showing that, on the average, close to four vectorial H+ are rejected per pair of electrons passing each of the three energy-conserving sites of the mitochondrial electron transport chain, direct tests of the H+/2e- ratio for sites 2 and 3 were carried out in the presence of permeant charge-compensating cations. Site 2 was examined by utilizing succinate as electron donor and ferricyanide as electron acceptor from mitochondrial cytochrome c; the directly measured H+/2e- ratio was close to 4. Energy-conserving site 3 was isolated for study with ferrocyanide or ascorbate plus tetramethylphenylenediamine as electron donors to cytochrome c and with oxygen as electron acceptor. The directly measured H+/2e- ratio for site 3 was close to 4. The H+/ATP ratio (number of vectorial H+ ejected per ATP hydrolyzed) was determined with a new method in which the steady-state rates of both H+ ejection and ATP hydrolysis were measured in the presence of K+ + valinomycin. The H+/ATP ratio was found to approach 3.0. A proton cycle for oxidative phosphorylation is proposed, in which four electrochemical H+ equivalents are ejected per pair of electrons passing each energy-conserving site; three of the H+ equivalents pass inward to derive ATP synthesis from ADP and phosphate and the fourth H+ is used to bring about the energy-requiring electrogenic expulsion of ATP4- in exchange for extramitochondrial ADP3-, via the H+/H2PO4- symporter. PMID:31621

  2. Copper(II) ions interactions in the systems with triamines and ATP. Potentiometric and spectroscopic studies.

    Science.gov (United States)

    Hoffmann, S K; Goslar, J; Bregier-Jarzebowska, R; Gasowska, A; Zalewska, A; Lomozik, L

    2017-12-01

    The mode of interaction and thermodynamic stability of complexes formed in binary and ternary Cu(II)/ATP/triamines systems were studied using potentiometric and spectroscopic (NMR, EPR, UV-Vis) methods. It was found that in binary metal-free systems ATP/H x PA species are formed (PA: Spd=spermidine or 3,3-tri=1,7-diamino-4-azaheptane) where the phosphate groups from nucleotides are preferred negative centers and protonated amine groups of amines are positive centers of reaction. In the ternary systems Cu/ATP/H x (PA) as well as Cu/(ATP)(PA) species are formed. The type of the formed Cu(II) complexes depends on pH of the solution. For a low pH value the complexation appears between Cu(II) and ATP molecules via oxygen atoms of phosphate groups. For a very high pH value, where ATP is hydrolyzed, the Cu(II) ions are bound to the nitrogen atoms of polyamine molecules. We did not detect any direct coordination of the N7 nitrogen atom of adenosine to Cu(II) ions. It means that the CuN7 interaction is an indirect type and can be due to noncovalent interplay including water molecule. EPR studies were performed at glassy state (77K) after a fast freezing both for binary and ternary systems. The glassy state EPR spectra do not reflect species identified in titration studies indicating significant effect of rapid temperature decrease on equilibrium of Cu(II) complexes. We propose the molecular structure of all the studied complexes at the glassy state deduced from EPR and optical spectroscopy results. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Periconceptional bread intakes indicate New Zealand's proposed mandatory folic acid fortification program may be outdated: results from a postpartum survey

    Science.gov (United States)

    2012-01-01

    Background In September 2009, a folic acid fortification mandate (135 μg/100 g bread) was to be implemented in New Zealand. However, due to political and manufacturer objection, fortification was deferred until May 2012. Based on estimates of bread consumption derived from a 1997 nationally representative survey, this program was intended to deliver a mean additional intake of 140 μg folic acid/d to women of childbearing age. Little is known about current bread consumption patterns in this target group. The aim of this study was to assess bread consumption among women prior to and during pregnancy with the intent to estimate periconceptional folic acid intakes that would be derived from bread if mandatory fortification were implemented as currently proposed. Methods A retrospective survey of 723 postpartum women in hospitals and birthing centres across New Zealand was conducted using a self-administered questionnaire on bread intake prior to and during pregnancy and maternal socio-demographic and obstetric characteristics. Results Median bread intake before conception (2 slices/d) was below that of previous data upon which the current fortification proposal was modeled (3-4 slices/d). If mandatory fortification is implemented as proposed, only 31% (95% CI = 24%-37%) of childbearing-age women would attain an additional folic acid intake of ≥ 140 μg/d, with a mean of 119 μg/d (95% CI = 107 μg/d-130 μg/d). Based on these data, a fortification level of 160 μg/100 g bread is required to achieve the targeted mean of 140 μg folic acid/d. Nonetheless, under the current proposal additional folic acid intakes would be greatest among the least advantaged segments of the target population: Pacific and indigenous Māori ethnic groups; those with increased parity, lower income and education; younger and single mothers; and women with unplanned pregnancies. Subgroups predicted to derive less than adequate folic acid intakes from the proposed policy were women of Asian

  4. Periconceptional bread intakes indicate New Zealand's proposed mandatory folic acid fortification program may be outdated: results from a postpartum survey.

    Science.gov (United States)

    Mallard, Simonette R; Gray, Andrew R; Houghton, Lisa A

    2012-02-14

    In September 2009, a folic acid fortification mandate (135 μg/100 g bread) was to be implemented in New Zealand. However, due to political and manufacturer objection, fortification was deferred until May 2012. Based on estimates of bread consumption derived from a 1997 nationally representative survey, this program was intended to deliver a mean additional intake of 140 μg folic acid/d to women of childbearing age. Little is known about current bread consumption patterns in this target group. The aim of this study was to assess bread consumption among women prior to and during pregnancy with the intent to estimate periconceptional folic acid intakes that would be derived from bread if mandatory fortification were implemented as currently proposed. A retrospective survey of 723 postpartum women in hospitals and birthing centres across New Zealand was conducted using a self-administered questionnaire on bread intake prior to and during pregnancy and maternal socio-demographic and obstetric characteristics. Median bread intake before conception (2 slices/d) was below that of previous data upon which the current fortification proposal was modeled (3-4 slices/d). If mandatory fortification is implemented as proposed, only 31% (95% CI = 24%-37%) of childbearing-age women would attain an additional folic acid intake of ≥ 140 μg/d, with a mean of 119 μg/d (95% CI = 107 μg/d-130 μg/d). Based on these data, a fortification level of 160 μg/100 g bread is required to achieve the targeted mean of 140 μg folic acid/d. Nonetheless, under the current proposal additional folic acid intakes would be greatest among the least advantaged segments of the target population: Pacific and indigenous Māori ethnic groups; those with increased parity, lower income and education; younger and single mothers; and women with unplanned pregnancies. Subgroups predicted to derive less than adequate folic acid intakes from the proposed policy were women of Asian descent and those with a

  5. Environmental program planning for the proposed high-level nuclear waste repository at Yucca Mountain, Nevada: Volume 1

    International Nuclear Information System (INIS)

    1987-08-01

    Environmental protection during the course of siting and constructing a repository is mandated by NWPA in conjunction with various phases of repository siting and development. However, DOE has issued no comprehensive, integrated plan for environmental protection. Consequently, it is unclear how DOE will accomplish environmental assessment, monitoring, impact mitigation, and site reclamation. DOE should, therefore, defer further implementation of its current characterization program until a comprehensive environmental protection plan is available. To fulfill its oversight responsibilities the State of Nevada has proposed a comprehensive environmental program for the Yucca Mountain site that includes immediately undertaking studies to establish a 12-month baseline of environmental information at the site; adopting the DOE Site Characterization Plan (SCP) and the engineering design plans it will contain as the basis for defining the impact potential of site characterization activities; using the environmental baseline and the SCP to evaluate the efficacy of the preliminary impact analyses reported by DOE in the EA; using the SCP as the basis for discussions with federal, state, and local regulatory authorities to decide which environmental requirements apply and how they can be complied with; using the SCP, the EA impact review, and the compliance requirements to determine the scope of reclamation measures needed; and developing environmental monitoring and impact mitigation plans based on the EA impact review, compliance requirements, and anticipated reclamation needs

  6. ATP7B detoxifies silver in ciliated airway epithelial cells

    International Nuclear Information System (INIS)

    Ibricevic, Aida; Brody, Steven L.; Youngs, Wiley J.; Cannon, Carolyn L.

    2010-01-01

    Silver is a centuries-old antibiotic agent currently used to treat infected burns. The sensitivity of a wide range of drug-resistant microorganisms to silver killing suggests that it may be useful for treating refractory lung infections. Toward this goal, we previously developed a methylated caffeine silver acetate compound, SCC1, that exhibits broad-spectrum antimicrobial activity against clinical strains of bacteria in vitro and when nebulized to lungs in mouse infection models. Preclinical testing of high concentrations of SCC1 in primary culture mouse tracheal epithelial cells (mTEC) showed selective ciliated cell death. Ciliated cell death was induced by both silver- and copper-containing compounds but not by the methylated caffeine portion of SCC1. We hypothesized that copper transporting P-type ATPases, ATP7A and ATP7B, play a role in silver detoxification in the airway. In mTEC, ATP7A was expressed in non-ciliated cells, whereas ATP7B was expressed only in ciliated cells. The exposure of mTEC to SCC1 induced the trafficking of ATP7B, but not ATP7A, suggesting the presence of a cell-specific silver uptake and detoxification mechanisms. Indeed, the expression of the copper uptake protein CTR1 was also restricted to ciliated cells. A role of ATP7B in silver detoxification was further substantiated when treatment of SCC1 significantly increased cell death in ATP7B shRNA-treated HepG2 cells. In addition, mTEC from ATP7B -/- mice showed enhanced loss of ciliated cells compared to wild type. These studies are the first to demonstrate a cell type-specific expression of the Ag + /Cu + transporters ATP7A, ATP7B, and CTR1 in airway epithelial cells and a role for ATP7B in detoxification of these metals in the lung.

  7. ATP release, generation and hydrolysis in exocrine pancreatic duct cells

    DEFF Research Database (Denmark)

    Kowal, Justyna Magdalena; Yegutkin, G.G.; Novak, Ivana

    2015-01-01

    Extracellular adenosine triphosphate (ATP) regulates pancreatic duct function via P2Y and P2X receptors. It is well known that ATP is released from upstream pancreatic acinar cells. The ATP homeostasis in pancreatic ducts, which secrete bicarbonate-rich fluid, has not yet been examined. First, ou...... may be important in pancreas physiology and potentially in pancreas pathophysiology....... aim was to reveal whether pancreatic duct cells release ATP locally and whether they enzymatically modify extracellular nucleotides/sides. Second, we wished to explore which physiological and pathophysiological factors may be important in these processes. Using a human pancreatic duct cell line, Capan...

  8. Application of luciferase assay for ATP to antimicrobial drug susceptibility

    Science.gov (United States)

    Chappelle, E. W.; Picciolo, G. L.; Vellend, H.; Tuttle, S. A.; Barza, M. J.; Weinstein, L. (Inventor)

    1977-01-01

    The susceptibility of bacteria, particularly those derived from body fluids, to antimicrobial agents is determined in terms of an ATP index measured by culturing a bacterium in a growth medium. The amount of ATP is assayed in a sample of the cultured bacterium by measuring the amount of luminescent light emitted when the bacterial ATP is reacted with a luciferase-luciferin mixture. The sample of the cultured bacterium is subjected to an antibiotic agent. The amount of bacterial adenosine triphosphate is assayed after treatment with the antibiotic by measuring the luminescent light resulting from the reaction. The ATP index is determined from the values obtained from the assay procedures.

  9. Binding of ATP by pertussis toxin and isolated toxin subunits

    International Nuclear Information System (INIS)

    Hausman, S.Z.; Manclark, C.R.; Burns, D.L.

    1990-01-01

    The binding of ATP to pertussis toxin and its components, the A subunit and B oligomer, was investigated. Whereas, radiolabeled ATP bound to the B oligomer and pertussis toxin, no binding to the A subunit was observed. The binding of [ 3 H]ATP to pertussis toxin and the B oligomer was inhibited by nucleotides. The relative effectiveness of the nucleotides was shown to be ATP > GTP > CTP > TTP for pertussis toxin and ATP > GTP > TTP > CTP for the B oligomer. Phosphate ions inhibited the binding of [ 3 H]ATP to pertussis toxin in a competitive manner; however, the presence of phosphate ions was essential for binding of ATP to the B oligomer. The toxin substrate, NAD, did not affect the binding of [ 3 H]ATP to pertussis toxin, although the glycoprotein fetuin significantly decreased binding. These results suggest that the binding site for ATP is located on the B oligomer and is distinct from the enzymatically active site but may be located near the eukaryotic receptor binding site

  10. Binding of ATP by pertussis toxin and isolated toxin subunits

    Energy Technology Data Exchange (ETDEWEB)

    Hausman, S.Z.; Manclark, C.R.; Burns, D.L. (Center for Biologics Evaluation and Research, Bethesda, MD (USA))

    1990-07-03

    The binding of ATP to pertussis toxin and its components, the A subunit and B oligomer, was investigated. Whereas, radiolabeled ATP bound to the B oligomer and pertussis toxin, no binding to the A subunit was observed. The binding of ({sup 3}H)ATP to pertussis toxin and the B oligomer was inhibited by nucleotides. The relative effectiveness of the nucleotides was shown to be ATP > GTP > CTP > TTP for pertussis toxin and ATP > GTP > TTP > CTP for the B oligomer. Phosphate ions inhibited the binding of ({sup 3}H)ATP to pertussis toxin in a competitive manner; however, the presence of phosphate ions was essential for binding of ATP to the B oligomer. The toxin substrate, NAD, did not affect the binding of ({sup 3}H)ATP to pertussis toxin, although the glycoprotein fetuin significantly decreased binding. These results suggest that the binding site for ATP is located on the B oligomer and is distinct from the enzymatically active site but may be located near the eukaryotic receptor binding site.

  11. Evidence for the Synthesis of ATP by an F0F1 ATP Synthase in Membrane Vesicles from Halorubrum Saccharovorum

    Science.gov (United States)

    Faguy, David; Lawson, Darion; Hochstein, Lawrence I.; Chang, Sherwood (Technical Monitor)

    1996-01-01

    Vesicles prepared in a buffer containing ADP, Mg(2+) and Pi synthesized ATP at an initial rate of 2 nmols/min/mg protein after acidification of the bulk medium (pH 8 (right arrow) 4). The intravesicular ATP concentration reached a steady state after about 30 seconds and slowly declined thereafter. ATP synthesis was inhibited by low concentrations of dicyclohexylcarbodiimide and m-chlorophenylhydrazone indicating that synthesis took place in response to the proton gradient. NEM and PCMS, which inhibit vacuolar ATPases and the vacuolar-like ATPases of extreme halophiles, did not affect ATP synthesis, and, in fact, produced higher steady state levels of ATP. This suggested that two ATPase activities were present, one which catalyzed ATP synthesis and one that caused its hydrolysis. Azide, a specific inhibitor of F0F1 ATP Synthases, inhibited halobacterial ATP synthesis. The distribution of acridine orange as imposed by a delta pH demonstrated that azide inhibition was not due to the collapse of the proton gradient due to azide acting as a protonophore. Such an effect was observed, but only at azide concentrations higher than those that inhibited ATP synthesis. These results confirm the earler observations with cells of H. saccharovorum and other extreme halophiles that ATP synthesis is inconsistent with the operation of a vacuolar-like ATPase. Therefore, the observation that a vacuolar-like enzyme is responsible for ATP synthesis (and which serves as the basis for imputing ATP synthesis to the vacuolar-like ATPases of the extreme halophiles, and the Archaea in general) should be taken with some degree of caution.

  12. Historical review: ATP as a neurotransmitter.

    Science.gov (United States)

    Burnstock, Geoffrey

    2006-03-01

    Purinergic signalling is now recognized to be involved in a wide range of activities of the nervous system, including neuroprotection, central control of autonomic functions, neural-glial interactions, control of vessel tone and angiogenesis, pain and mechanosensory transduction and the physiology of the special senses. In this article, I give a personal retrospective of the discovery of purinergic neurotransmission in the early 1970s, the struggle for its acceptance for approximately 20 years, the expansion into purinergic cotransmission and its eventual acceptance when receptor subtypes for ATP were cloned and characterized and when purinergic synaptic transmission between neurons in the brain and peripheral ganglia was described in the early 1990s. I also discuss the current status of the field, including recent interest in the pathophysiology of purinergic signalling and its therapeutic potential.

  13. Connexin hemichannel-mediated CO2-dependent release of ATP in the medulla oblongata contributes to central respiratory chemosensitivity

    Science.gov (United States)

    Huckstepp, Robert T R; id Bihi, Rachid; Eason, Robert; Spyer, K Michael; Dicke, Nikolai; Willecke, Klaus; Marina, Nephtali; Gourine, Alexander V; Dale, Nicholas

    2010-01-01

    Arterial , a major determinant of breathing, is detected by chemosensors located in the brainstem. These are important for maintaining physiological levels of in the blood and brain, yet the mechanisms by which the brain senses CO2 remain controversial. As ATP release at the ventral surface of the brainstem has been causally linked to the adaptive changes in ventilation in response to hypercapnia, we have studied the mechanisms of CO2-dependent ATP release in slices containing the ventral surface of the medulla oblongata. We found that CO2-dependent ATP release occurs in the absence of extracellular acidification and correlates directly with the level of . ATP release is independent of extracellular Ca2+ and may occur via the opening of a gap junction hemichannel. As agents that act on connexin channels block this release, but compounds selective for pannexin-1 have no effect, we conclude that a connexin hemichannel is involved in CO2-dependent ATP release. We have used molecular, genetic and immunocytochemical techniques to demonstrate that in the medulla oblongata connexin 26 (Cx26) is preferentially expressed near the ventral surface. The leptomeninges, subpial astrocytes and astrocytes ensheathing penetrating blood vessels at the ventral surface of the medulla can be loaded with dye in a CO2-dependent manner, suggesting that gating of a hemichannel is involved in ATP release. This distribution of CO2-dependent dye loading closely mirrors that of Cx26 expression and colocalizes to glial fibrillary acidic protein (GFAP)-positive cells. In vivo, blockers with selectivity for Cx26 reduce hypercapnia-evoked ATP release and the consequent adaptive enhancement of breathing. We therefore propose that Cx26-mediated release of ATP in response to changes in is an important mechanism contributing to central respiratory chemosensitivity. PMID:20736421

  14. Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2

    Directory of Open Access Journals (Sweden)

    Quadros Edward V

    2009-05-01

    Full Text Available Abstract Background Recent evidence suggests that several human cancers are capable of uncoupling of mitochondrial ATP generation in the presence of intact tricarboxylic acid (TCA enzymes. The goal of the current study was to test the hypothesis that ketone bodies can inhibit cell growth in aggressive cancers and that expression of uncoupling protein 2 is a contributing factor. The proposed mechanism involves inhibition of glycolytic ATP production via a Randle-like cycle while increased uncoupling renders cancers unable to produce compensatory ATP from respiration. Methods Seven aggressive human cancer cell lines, and three control fibroblast lines were grown in vitro in either 10 mM glucose medium (GM, or in glucose plus 10 mM acetoacetate [G+AcA]. The cells were assayed for cell growth, ATP production and expression of UCP2. Results There was a high correlation of cell growth with ATP concentration (r = 0.948 in a continuum across all cell lines. Controls demonstrated normal cell growth and ATP with the lowest density of mitochondrial UCP2 staining while all cancer lines demonstrated proportionally inhibited growth and ATP, and over-expression of UCP2 (p Conclusion Seven human cancer cell lines grown in glucose plus acetoacetate medium showed tightly coupled reduction of growth and ATP concentration. The findings were not observed in control fibroblasts. The observed over-expression of UCP2 in cancer lines, but not in controls, provides a plausible molecular mechanism by which acetoacetate spares normal cells but suppresses growth in cancer lines. The results bear on the hypothesized potential for ketogenic diets as therapeutic strategies.

  15. Nullius in verba: The University of Minnesota Social and Administrative Pharmacy Program proposed Guidelines for Formulary Evaluations

    Directory of Open Access Journals (Sweden)

    Paul C Langley

    2016-07-01

    Full Text Available The University of Minnesota Social and Administrative Pharmacy Program proposed Guidelines for Formulary Evaluations (GFE are designed to focus on the credibility of clinical and cost-outcomes claims in formulary decision making. The last few years have witnessed increasing concern over the credibility of trial based efficacy claims, with a surprisingly high proportion of claims falling short. At the same time cost-outcomes claims, where comparative clinical claims are a key input, have been presented where the claims made are not open to experimental or observational assessment. This follows from standards recommended for modeled and simulated claims. In the absence of cost-outcomes claims being presented in an evaluable form, it is impossible not only to replicate the claim or to judge whether or not it is credible. Claims for product value based on such claims are unacceptable. The guidelines proposed here are designed to overcome these limitations and support an evidence base that is both credible and replicable for formulary decisions. This is achieved by focusing on short-term modeled or simulated claims for cost-effectiveness. The requirement for modeled or simulated claims that are evaluable within a time frame that is meaningful for formulary decisions marks a major departure from format submissions already in play, not only in the US but in other developed economies. Rather than subscribing to the gold standard of long term or lifetime cost-per-QALY claims a short-term time horizon of no more than 2-years is recommended. This allows products to be provisionally placed on formulary but subject to a protocol that supports an evaluation to be reported back to a formulary committee as part of ongoing disease area or therapeutic class reviews. The place of the product and its contracted price can then be reviewed. Conflict of Interest None Type: Commentary

  16. Coordination of substrate binding and ATP hydrolysis in Vps4-mediated ESCRT-III disassembly.

    Science.gov (United States)

    Davies, Brian A; Azmi, Ishara F; Payne, Johanna; Shestakova, Anna; Horazdovsky, Bruce F; Babst, Markus; Katzmann, David J

    2010-10-01

    ESCRT-III undergoes dynamic assembly and disassembly to facilitate membrane exvagination processes including multivesicular body (MVB) formation, enveloped virus budding, and membrane abscission during cytokinesis. The AAA-ATPase Vps4 is required for ESCRT-III disassembly, however the coordination of Vps4 ATP hydrolysis with ESCRT-III binding and disassembly is not understood. Vps4 ATP hydrolysis has been proposed to execute ESCRT-III disassembly as either a stable oligomer or an unstable oligomer whose dissociation drives ESCRT-III disassembly. An in vitro ESCRT-III disassembly assay was developed to analyze Vps4 function during this process. The studies presented here support a model in which Vps4 acts as a stable oligomer during ATP hydrolysis and ESCRT-III disassembly. Moreover, Vps4 oligomer binding to ESCRT-III induces coordination of ATP hydrolysis at the level of individual Vps4 subunits. These results suggest that Vps4 functions as a stable oligomer that acts upon individual ESCRT-III subunits to facilitate ESCRT-III disassembly.

  17. A novel ATP1A2 gene mutation in an Irish familial hemiplegic migraine kindred.

    LENUS (Irish Health Repository)

    Fernandez, Desiree M

    2012-02-03

    OBJECTIVE: We studied a large Irish Caucasian pedigree with familial hemiplegic migraine (FHM) with the aim of finding the causative gene mutation. BACKGROUND: FHM is a rare autosomal-dominant subtype of migraine with aura, which is linked to 4 loci on chromosomes 19p13, 1q23, 2q24, and 1q31. The mutations responsible for hemiplegic migraine have been described in the CACNA1A gene (chromosome 19p13), ATP1A2 gene (chromosome 1q23), and SCN1A gene (chromosome 2q24). METHODS: We performed linkage analyses in this family for chromosome 1q23 and performed mutation analysis of the ATP1A2 gene. RESULTS: Linkage to the FHM2 locus on chromosome 1 was demonstrated. Mutation screening of the ATP1A2 gene revealed a G to C substitution in exon 22 resulting in a novel protein variant, D999H, which co-segregates with FHM within this pedigree and is absent in 50 unaffected individuals. This residue is also highly conserved across species. CONCLUSIONS: We propose that D999H is a novel FHM ATP1A2 mutation.

  18. In vivo inhibition of the mitochondrial H+-ATP synthase in neurons promotes metabolic preconditioning.

    Science.gov (United States)

    Formentini, Laura; Pereira, Marta P; Sánchez-Cenizo, Laura; Santacatterina, Fulvio; Lucas, José J; Navarro, Carmen; Martínez-Serrano, Alberto; Cuezva, José M

    2014-04-01

    A key transducer in energy conservation and signaling cell death is the mitochondrial H(+)-ATP synthase. The expression of the ATPase inhibitory factor 1 (IF1) is a strategy used by cancer cells to inhibit the activity of the H(+)-ATP synthase to generate a ROS signal that switches on cellular programs of survival. We have generated a mouse model expressing a mutant of human IF1 in brain neurons to assess the role of the H(+)-ATP synthase in cell death in vivo. The expression of hIF1 inhibits the activity of oxidative phosphorylation and mediates the shift of neurons to an enhanced aerobic glycolysis. Metabolic reprogramming induces brain preconditioning affording protection against quinolinic acid-induced excitotoxicity. Mechanistically, preconditioning involves the activation of the Akt/p70S6K and PARP repair pathways and Bcl-xL protection from cell death. Overall, our findings provide the first in vivo evidence highlighting the H(+)-ATP synthase as a target to prevent neuronal cell death.

  19. Mevalonate 5-diphosphate mediates ATP binding to the mevalonate diphosphate decarboxylase from the bacterial pathogen Enterococcus faecalis

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chun-Liang; Mermoud, James C.; Paul, Lake N.; Steussy, Calvin Nicklaus; Stauffacher, Cynthia V. (Purdue)

    2017-10-12

    The mevalonate pathway produces isopentenyl diphosphate (IPP), a building block for polyisoprenoid synthesis, and is a crucial pathway for growth of the human bacterial pathogen Enterococcus faecalis. The final enzyme in this pathway, mevalonate diphosphate decarboxylase (MDD), acts on mevalonate diphosphate (MVAPP) to produce IPP while consuming ATP. This essential enzyme has been suggested as a therapeutic target for the treatment of drug-resistant bacterial infections. Here, we report functional and structural studies on the mevalonate diphosphate decarboxylase from E. faecalis (MDDEF). The MDDEF crystal structure in complex with ATP (MDDEF–ATP) revealed that the phosphate-binding loop (amino acids 97–105) is not involved in ATP binding and that the phosphate tail of ATP in this structure is in an outward-facing position pointing away from the active site. This suggested that binding of MDDEF to MVAPP is necessary to guide ATP into a catalytically favorable position. Enzymology experiments show that the MDDEF performs a sequential ordered bi-substrate reaction with MVAPP as the first substrate, consistent with the isothermal titration calorimetry (ITC) experiments. On the basis of ITC results, we propose that this initial prerequisite binding of MVAPP enhances ATP binding. In summary, our findings reveal a substrate-induced substrate-binding event that occurs during the MDDEF-catalyzed reaction. The disengagement of the phosphate-binding loop concomitant with the alternative ATP-binding configuration may provide the structural basis for antimicrobial design against these pathogenic enterococci.

  20. Environmental considerations for inclusion in program opportunity notices, requests for proposals, and environmental reports: fossil energy demonstration plants

    Energy Technology Data Exchange (ETDEWEB)

    Salk, M.S.; Baird, J.N.; Barnthouse, L.W.; Berry, L.G.; Roop, R.D.; Sanders, F.S.

    1978-01-01

    This document was prepared for the Department of Energy, Division of Coal Conversion, for use in developing Program Opportunity Notices (PON), Requests for Proposals (RFP), and Environmental Reports (ER). Environmental considerations to be addressed by Offerors and Contractors are divided into three parts that correspond to the separate stages of project development: (1) the Offeror's response to the PON or RFP; (2) the Contractor's performance of baseline data collection and environmental impact assessment that results in an Environmental Report (ER) for use by DOE in the preparation of an Environmental Impact Statement (EIS); and (3) the Contractor's continuance of environmental monitoring and assessment during construction and operation. Environmental analysis and environmental protection are an integral part of the Offeror's or Contractor's performance under contract to DOE. Consideration should be given to the health and socioeconomic status of man as well as to the physical and biological environment. The Offeror's or Contractor's consideration of and commitment to avoiding adverse environmental impacts must be demonstrated at every stage of the process from planning through construction and operation.

  1. ATP storage and uptake by isolated pancreatic zymogen granules

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Novak, Ivana

    2010-01-01

    ATP is released from pancreatic acini in response to cholinergic and hormonal stimulation. The same stimuli cause exocytosis of ZG (zymogen granules) and release of digestive enzymes. The aim of the present study was to determine whether ZG stored ATP and to characterize the uptake mechanism for ...

  2. Renal epithelial cells can release ATP by vesicular fusion

    Directory of Open Access Journals (Sweden)

    Randi G Bjaelde

    2013-09-01

    Full Text Available Renal epithelial cells have the ability to release nucleotides as paracrine factors. In the intercalated cells of the collecting duct, ATP is released by connexin30 (cx30, which is selectively expressed in this cell type. However, ATP is released by virtually all renal epithelia and the aim of the present study was to identify possible alternative nucleotide release pathways in a renal epithelial cell model. We used MDCK (type1 cells to screen for various potential ATP release pathways. In these cells, inhibition of the vesicular H+-ATPases (bafilomycin reduced both the spontaneous and hypotonically (80%-induced nucleotide release. Interference with vesicular fusion using N-ethylamide markedly reduced the spontaneous nucleotide release, as did interference with trafficking from the endoplasmic reticulum to the Golgi apparatus (brefeldin A1 and vesicular transport (nocodazole. These findings were substantiated using a siRNA directed against SNAP-23, which significantly reduced spontaneous ATP release. Inhibition of pannexin and connexins did not affect the spontaneous ATP release in this cell type, which consists of ∼90% principal cells. TIRF-microscopy of either fluorescently-labeled ATP (MANT-ATP or quinacrine-loaded vesicles, revealed that spontaneous release of single vesicles could be promoted by either hypoosmolality (50% or ionomycin. This vesicular release decreased the overall cellular fluorescence by 5.8% and 7.6% respectively. In summary, this study supports the notion that spontaneous and induced ATP release can occur via exocytosis in renal epithelial cells.

  3. ATP synthase--a marvellous rotary engine of the cell.

    Science.gov (United States)

    Yoshida, M; Muneyuki, E; Hisabori, T

    2001-09-01

    ATP synthase can be thought of as a complex of two motors--the ATP-driven F1 motor and the proton-driven Fo motor--that rotate in opposite directions. The mechanisms by which rotation and catalysis are coupled in the working enzyme are now being unravelled on a molecular scale.

  4. ATP economy of force maintenance in human tibialis anterior muscle

    DEFF Research Database (Denmark)

    Nakagawa, Yoshinao; Ratkevicius, Aivaras; Mizuno, Masao

    2005-01-01

    PURPOSE: The aim of this study was investigate ATP economy of force maintenance in the human tibialis anterior muscle during 60 s of anaerobic voluntary contraction at 50% of maximum voluntary contraction (MVC). METHODS: ATP turnover rate was evaluated using P magnetic resonance spectroscopy (P...... contraction. It averaged at 4.81 +/- 0.42 N.s.micromol-1, and correlated with the relative cross-sectional area of the muscle occupied by Type I fiber (r = 0.73, P contraction, subjects dropping in force showed lower ATP economy compared with those maintaining the force (3.......7 +/- 0.6 vs 5.3 +/- 0.6 N.s.micromol-1; P contraction could be due to an increase in the ATP economy of contracting muscle fibers offsetting the effects of increased temperature and low ATP economy...

  5. Regulatory acceptance of the proposed well abandonment program for the present landfill, Operable Unit 7, Rocky Flats Environmental Technology Site, Golden, Colorado

    International Nuclear Information System (INIS)

    Wood, M.R.

    1995-01-01

    The regulatory agencies approved a well abandonment program for the Present Landfill, Operable Unit (OU) 7 at the Rocky Flats Environmental Technology Site, only three months after preparation. The proposed well abandonment program consists of abandoning 26 of the 54 existing monitoring wells in OU 7 that are currently sampled quarterly as Resource Conservation and Recovery Act (RCRA) compliance wells or sitewide groundwater protection wells. Well abandonment was proposed on the basis that the purpose of each well has been fulfilled, the wells fall under the footprint of the landfill cap, the presence of the wells would compromise the integrity of the cap because holes would have to be cut in the synthetic liner, and unequal compaction of the fill material around the wells would potentially cause differential settlement of the cap. The proposal provided the technical justification to abandon the wells in place. The timely approval of the proposal by the regulatory agencies will allow the abandonment of the wells during fiscal year 1995 under the sitewide Well Abandonment and Replacement Program (WARP). Cost savings resulting from a decrease in the number of wells to be sampled under the groundwater monitoring program are estimated at $416,000 per year. This paper presents a summary of the well abandonment program, discusses the timely approvals required for implementation, and present the potential cost savings that can be achieved through implementation of the program

  6. Calcium regulates ATP-sensitive microtubule binding by Chlamydomonas outer arm dynein.

    Science.gov (United States)

    Sakato, Miho; King, Stephen M

    2003-10-31

    The Chlamydomonas outer dynein arm contains three distinct heavy chains (alpha, beta, and gamma) that exhibit different motor properties. The LC4 protein, which binds 1-2 Ca2+ with KCa = 3 x 10-5 m, is associated with the gamma heavy chain and has been proposed to act as a sensor to regulate dynein motor function in response to alterations in intraflagellar Ca2+ levels. Here we genetically dissect the outer arm to yield subparticles containing different motor unit combinations and assess the microtubule-binding properties of these complexes both prior to and following preincubation with tubulin and ATP, which was used to inhibit ATP-insensitive (structural) microtubule binding. We observed that the alpha heavy chain exhibits a dominant Ca2+-independent ATP-sensitive MT binding activity in vitro that is inhibited by attachment of tubulin to the structural microtubule-binding domain. Furthermore, we show that ATP-sensitive microtubule binding by a dynein subparticle containing only the beta and gamma heavy chains does not occur at Ca2+ concentrations below pCa 6 but is maximally activated above pCa 5. This activity was not observed in mutant dyneins containing small deletions in the microtubule-binding region of the beta heavy chain or in dyneins that lack both the alpha heavy chain and the motor domain of the beta heavy chain. These findings strongly suggest that Ca2+ binding directly to a component of the dynein complex regulates ATP-sensitive interactions between the beta heavy chain and microtubules and lead to a model for how individual motor units are controlled within the outer dynein arm.

  7. P2X receptor-mediated ATP purinergic signaling in health and disease

    Directory of Open Access Journals (Sweden)

    Jiang LH

    2012-09-01

    Full Text Available Lin-Hua JiangSchool of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomAbstract: Purinergic P2X receptors are plasma membrane proteins present in a wide range of mammalian cells where they act as a cellular sensor, enabling cells to detect and respond to extracellular adenosine triphosphate (ATP, an important signaling molecule. P2X receptors function as ligand-gated Ca2+-permeable cationic channels that open upon ATP binding to elevate intracellular Ca2+ concentrations and cause membrane depolarization. In response to sustained activation, P2X receptors induce formation of a pore permeable to large molecules. P2X receptors also interact with distinct functional proteins and membrane lipids to form specialized signaling complexes. Studies have provided compelling evidence to show that such P2X receptor-mediated ATP-signaling mechanisms determine and regulate a growing number and diversity of important physiological processes, including neurotransmission, muscle contraction, and cytokine release. There is accumulating evidence to support strong causative relationships of altered receptor expression and function with chronic pain, inflammatory diseases, cancers, and other pathologies or diseases. Numerous high throughput screening drug discovery programs and preclinical studies have thus far demonstrated the proof of concepts that the P2X receptors are druggable targets and selective receptor antagonism is a promising therapeutics approach. This review will discuss the recent progress in understanding the mammalian P2X receptors with respect to the ATP-signaling mechanisms, physiological and pathophysiological roles, and development and preclinical studies of receptor antagonists.Keywords: extracellular ATP, ion channel, large pore, signaling complex, chronic pain, inflammatory diseases

  8. Differential expression of ATP7A, ATP7B and CTR1 in adult rat dorsal root ganglion tissue

    Directory of Open Access Journals (Sweden)

    Ip Virginia

    2010-09-01

    Full Text Available Abstract Background ATP7A, ATP7B and CTR1 are metal transporting proteins that control the cellular disposition of copper and platinum drugs, but their expression in dorsal root ganglion (DRG tissue and their role in platinum-induced neurotoxicity are unknown. To investigate the DRG expression of ATP7A, ATP7B and CTR1, lumbar DRG and reference tissues were collected for real time quantitative PCR, RT-PCR, immunohistochemistry and Western blot analysis from healthy control adult rats or from animals treated with intraperitoneal oxaliplatin (1.85 mg/kg or drug vehicle twice weekly for 8 weeks. Results In DRG tissue from healthy control animals, ATP7A mRNA was clearly detectable at levels similar to those found in the brain and spinal cord, and intense ATP7A immunoreactivity was localised to the cytoplasm of cell bodies of smaller DRG neurons without staining of satellite cells, nerve fibres or co-localisation with phosphorylated heavy neurofilament subunit (pNF-H. High levels of CTR1 mRNA were detected in all tissues from healthy control animals, and strong CTR1 immunoreactivity was associated with plasma membranes and vesicular cytoplasmic structures of the cell bodies of larger-sized DRG neurons without co-localization with ATP7A. DRG neurons with strong expression of ATP7A or CTR1 had distinct cell body size profiles with minimal overlap between them. Oxaliplatin treatment did not alter the size profile of strongly ATP7A-immunoreactive neurons but significantly reduced the size profile of strongly CTR1-immunoreactive neurons. ATP7B mRNA was barely detectable, and no specific immunoreactivity for ATP7B was found, in DRG tissue from healthy control animals. Conclusions In conclusion, adult rat DRG tissue exhibits a specific pattern of expression of copper transporters with distinct subsets of peripheral sensory neurons intensely expressing either ATP7A or CTR1, but not both or ATP7B. The neuron subtype-specific and largely non

  9. The research design: a proposal for integration in the third year of the program of physical culture

    Directory of Open Access Journals (Sweden)

    Marbelia Cantillo Vento

    2016-08-01

    Full Text Available In order to achieve a future competent graduate from the Faculty of Physical Culture (FPC, it is important to develop a high quality teaching, where the evaluation is the component of the PDE, that allows issuing a valuable judgment about the appropriation of knowledge. Under the assumption that the evaluation is «a complex and continuous process of assessment of pedagogical situations, their results and the contexts and conditions in which they occur. In this framework, we propose the significance and meaning of «integrative evaluation», which is a privileged integrator moment in the process of construction of scholar knowledge. Even if, the integrative evaluation may be considered in a clearly differentiated moment, its construction may face a procedural and final character. Taking this definition as a starting point and taking into consideration the major shortcomings shown in previous exercises, we find that there are: -limitations when addressing the evaluations, that aim a content integration, -insufficient integration of previous knowledge knowledge and the role of the students, -poor guidance to follow the logic of the systematic principle, and the spiral evolution of knowledge by transferring the knowledge to new situations, -difficulties in building a reflective and creative thinking, that allows the student to «get to the core», by establishing links and relationships, necessary to apply the content to social practice, so that it gives solutions to problems in general. The following investigation aim to find an approach to a more efficient and integrating exam in the third year of the program of Physical Culture.

  10. 77 FR 27266 - 60-Day Notice of Proposed Information Collection: Form DS-4213, PEPFAR Program Expenditures; OMB...

    Science.gov (United States)

    2012-05-09

    ... information about program costs under PEPFAR on a global level. Applying expenditure results will improve... the global response to HIV/AIDS. In order to improve program monitoring, the Finance and Economics... partners in countries with PEPFAR programs using a standard tool (DS-4213) via an electronic interface...

  11. 78 FR 6851 - Proposed Information Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program...

    Science.gov (United States)

    2013-01-31

    ... (Patient Satisfaction Survey Michael E. DeBakey Home Care Program) Activity: Comment Request AGENCY... Satisfaction Survey Michael E. DeBakey Home Care Program, VA Form 10-0476. OMB Control Number: 2900-0775. Type... home care program staff. An agency may not conduct or sponsor, and a person is not required to respond...

  12. 78 FR 65696 - 30-Day Notice of Proposed Information Collection: Housing Finance Agency Risk-Sharing Program

    Science.gov (United States)

    2013-11-01

    ... Information Collection: Housing Finance Agency Risk-Sharing Program AGENCY: Office of the Chief Information... Information Collection: Housing Finance Agency Risk- Sharing Program. OMB Approval Number: 2502-0500. Type of... housing finance agencies (HFAs). Under this program, HUD provides full mortgage insurance on multifamily...

  13. 78 FR 64145 - 30-Day Notice of Proposed Information Collection: Housing Finance Agency Risk-Sharing Program

    Science.gov (United States)

    2013-10-25

    ... Information Collection: Housing Finance Agency Risk-Sharing Program AGENCY: Office of the Chief Information... Title of Information Collection: Housing Finance Agency Risk- Sharing Program. OMB Approval Number: 2502... sharing with State and local housing finance agencies (HFAs). Under this program, HUD provides full...

  14. 78 FR 52962 - 60-Day Notice of Proposed Information Collection: Housing Finance Agency Risk-Sharing Program

    Science.gov (United States)

    2013-08-27

    ... Information Collection: Housing Finance Agency Risk-Sharing Program AGENCY: Office of the Assistant Secretary... Finance Agency Risk- Sharing Program. OMB Approval Number: 2502-0500. Type of Request (i.e. new, revision... Secretary to implement risk sharing with State and local housing finance agencies (HFAs). Under this program...

  15. 75 FR 22423 - Pick-Sloan Missouri Basin Program, Eastern and Western Division Proposed Project Use Power Rate

    Science.gov (United States)

    2010-04-28

    ...: Reopening of comment period for review of the Pick-Sloan Missouri Basin Program, Eastern and Western... reopening the comment period for the Pick-Sloan Missouri Basin Program, Eastern and Western Division... DEPARTMENT OF THE INTERIOR Bureau of Reclamation Pick-Sloan Missouri Basin Program, Eastern and...

  16. Selection methodology for LWR safety R and D programs and proposals. Volume III. User's manual for the multi-attribute utility package (MAUP)

    International Nuclear Information System (INIS)

    Hale, M.; Turnage, J.J.; Husseiny, A.A.; Ritzman, R.L.

    1981-02-01

    The computer program which was developed to apply the multi-attribute utility (MAU) methodology to the selection of LWR safety R and D programs and proposals is described. An overview of the MAU method is presented, followed by a description of the steps incorporated in developing individual modules for use in the multi-attribute utility package (MAUP). Each module is described complete with usage information and an example of computer output

  17. Quantal release of ATP from clusters of PC12 cells.

    Science.gov (United States)

    Fabbro, Alessandra; Skorinkin, Andrei; Grandolfo, Micaela; Nistri, Andrea; Giniatullin, Rashid

    2004-10-15

    Although ATP is important for intercellular communication, little is known about the mechanism of endogenous ATP release due to a dearth of suitable models. Using PC12 cells known to express the P2X2 subtype of ATP receptors and to store ATP with catecholamines inside dense-core vesicles, we found that clusters of PC12 cells cultured for 3-7 days generated small transient inward currents (STICs) after an inward current elicited by exogenous ATP. The amplitude of STICs in individual cells correlated with the peak amplitude of ATP-induced currents. STICs appeared as asynchronous responses (approximately 20 pA average amplitude) for 1-20 s and were investigated with a combination of patch clamping, Ca2+ imaging, biochemistry and electron microscopy. Comparable STICs were produced by focal KCl pulses and were dependent on extracellular Ca2+. STICs were abolished by the P2X antagonist PPADS and potentiated by Zn2+, suggesting they were mediated by P2X2 receptor activation. The highest probability of observing STICs was after the peak of intracellular Ca2+ increase caused by KCl. Biochemical measurements indicated that KCl application induced a significant release of ATP from PC12 cells. Electron microscopy studies showed narrow clefts without 'synaptic-like' densities between clustered cells. Our data suggest that STICs were caused by quantal release of endogenous ATP by depolarized PC12 cells in close juxtaposition to the recorded cell. Thus, STICs may be a new experimental model to characterize the physiology of vesicular release of ATP and to study the kinetics and pharmacology of P2X2 receptor-mediated quantal currents.

  18. Mycobacterium tuberculosis Universal Stress Protein Rv2623 Regulates Bacillary Growth by ATP Binding: Requirement for Establishing Chronic Persistent Infection

    Energy Technology Data Exchange (ETDEWEB)

    Drumm, J.; Mi, K; Bilder, P; Sun, M; Lim, J; Bielefeldt-Ohmann, H; Basaraba, R; So, M; Zhu, G; et. al.

    2009-01-01

    Tuberculous latency and reactivation play a significant role in the pathogenesis of tuberculosis, yet the mechanisms that regulate these processes remain unclear. The Mycobacterium tuberculosisuniversal stress protein (USP) homolog, rv2623, is among the most highly induced genes when the tubercle bacillus is subjected to hypoxia and nitrosative stress, conditions thought to promote latency. Induction of rv2623 also occurs when M. tuberculosis encounters conditions associated with growth arrest, such as the intracellular milieu of macrophages and in the lungs of mice with chronic tuberculosis. Therefore, we tested the hypothesis that Rv2623 regulates tuberculosis latency. We observed that an Rv2623-deficient mutant fails to establish chronic tuberculous infection in guinea pigs and mice, exhibiting a hypervirulence phenotype associated with increased bacterial burden and mortality. Consistent with this in vivo growth-regulatory role, constitutive overexpression of rv2623 attenuates mycobacterial growth in vitro. Biochemical analysis of purified Rv2623 suggested that this mycobacterial USP binds ATP, and the 2.9-A-resolution crystal structure revealed that Rv2623 engages ATP in a novel nucleotide-binding pocket. Structure-guided mutagenesis yielded Rv2623 mutants with reduced ATP-binding capacity. Analysis of mycobacteria overexpressing these mutants revealed that the in vitro growth-inhibitory property of Rv2623 correlates with its ability to bind ATP. Together, the results indicate that i M. tuberculosis Rv2623 regulates mycobacterial growth in vitro and in vivo, and ii Rv2623 is required for the entry of the tubercle bacillus into the chronic phase of infection in the host; in addition, iii Rv2623 binds ATP; and iv the growth-regulatory attribute of this USP is dependent on its ATP-binding activity. We propose that Rv2623 may function as an ATP-dependent signaling intermediate in a pathway that promotes persistent infection.

  19. Adenosine Triphosphate (ATP Is a Candidate Signaling Molecule in the Mitochondria-to-Nucleus Retrograde Response Pathway

    Directory of Open Access Journals (Sweden)

    Zhengchang Liu

    2013-03-01

    Full Text Available Intracellular communication from the mitochondria to the nucleus is achieved via the retrograde response. In budding yeast, the retrograde response, also known as the RTG pathway, is regulated positively by Rtg1, Rtg2, Rtg3 and Grr1 and negatively by Mks1, Lst8 and two 14-3-3 proteins, Bmh1/2. Activation of retrograde signaling leads to activation of Rtg1/3, two basic helix-loop-helix leucine zipper transcription factors. Rtg1/3 activation requires Rtg2, a cytoplasmic protein with an N-terminal adenosine triphosphate (ATP binding domain belonging to the actin/Hsp70/sugar kinase superfamily. The critical regulatory step of the retrograde response is the interaction between Rtg2 and Mks1. Rtg2 binds to and inactivates Mks1, allowing for activation of Rtg1/3 and the RTG pathway. When the pathway is inactive, Mks1 has dissociated from Rtg2 and bound to Bmh1/2, preventing activation of Rtg1/3. What signals association or disassociation of Mks1 and Rtg2 is unknown. Here, we show that ATP at physiological concentrations dissociates Mks1 from Rtg2 in a highly cooperative fashion. We report that ATP-mediated dissociation of Mks1 from Rtg2 is conserved in two other fungal species, K. lactis and K. waltii. Activation of Rtg1/3 upregulates expression of genes encoding enzymes catalyzing the first three reactions of the Krebs cycle, which is coupled to ATP synthesis through oxidative phosphorylation. Therefore, we propose that the retrograde response is an ATP homeostasis pathway coupling ATP production with ATP-mediated repression of the retrograde response by releasing Mks1 from Rtg2.

  20. Spectrographic study of neodymium complexing with ATP and ADP

    International Nuclear Information System (INIS)

    Svetlova, I.E.; Dobrynina, N.A.; Martynenko, L.N.

    1989-01-01

    By spectrographic method neodymium complexing with ATP and ADP in aqueous solutions at different pH values has been studied. The composition of the complexes was determined by the method of isomolar series. On the basis of analysis of absorption spectra it has been ascertained that at equimolar ratio of Nd 3+ and ATP absorption band of L278A corresponds to monocomplex, and the band of 4290 A - to biscomplex. For the complexes with ADP the absorption band of 4288 A is referred to bicomplexes. The character of ATP and ADP coordination by Nd 3+ ion is considered. Stability constants of the complexes are calculated

  1. Lowest Price, Technically Acceptable Evaluation Criteria Used in the November 2014 Request for Proposal for the Program Executive Office Soldier Systems Engineering and Technical Assistance (SETA) Contract

    Science.gov (United States)

    2017-09-01

    GS-0895-09 Industrial Engineering Technician 23.04 7.56 GS-0810-09 Civil Engineering Developmental (Programming) 23.04 7.56 GS-0810-11 Civil ... Engineering –Programming 27.88 9.14 GS-0810-12 Civil Engineering –Design 33.41 10.96 GS-2210-09 Info Tech Spec (Network Systems/Customer Support) 23.04...USED IN THE NOVEMBER 2014 REQUEST FOR PROPOSAL FOR THE PROGRAM EXECUTIVE OFFICE SOLDIER SYSTEMS ENGINEERING AND TECHNICAL ASSISTANCE (SETA) CONTRACT

  2. Ketogenic diet metabolites reduce firing in central neurons by opening K(ATP) channels.

    Science.gov (United States)

    Ma, Weiyuan; Berg, Jim; Yellen, Gary

    2007-04-04

    A low-carbohydrate ketogenic diet remains one of the most effective (but mysterious) treatments for severe pharmacoresistant epilepsy. We have tested for an acute effect of physiological ketone bodies on neuronal firing rates and excitability, to discover possible therapeutic mechanisms of the ketogenic diet. Physiological concentrations of ketone bodies (beta-hydroxybutyrate or acetoacetate) reduced the spontaneous firing rate of neurons in slices from rat or mouse substantia nigra pars reticulata. This region is thought to act as a "seizure gate," controlling seizure generalization. Consistent with an anticonvulsant role, the ketone body effect is larger for cells that fire more rapidly. The effect of ketone bodies was abolished by eliminating the metabolically sensitive K(ATP) channels pharmacologically or by gene knock-out. We propose that ketone bodies or glycolytic restriction treat epilepsy by augmenting a natural activity-limiting function served by K(ATP) channels in neurons.

  3. Teaching Education and Socio-educational Action: Developing an Implementation Proposal of the Program Community Teachers (PCT

    Directory of Open Access Journals (Sweden)

    Paulette Barberousse-Alfonso

    2017-12-01

    Full Text Available From a critical and transformative approach, this essay presents inputs and relevant conclusions obtained during the first stage of the project Construyendo una propuesta de implementación del Programa Maestros Comunitarios (PMC, Code number 0166-15 DEB-UNA (UNA, DEB, s. f., conducted in 2016. Considering our perspective as researchers and professors at División de Educación Básica, the paper addresses a current topic within the socio-educative field to face challenges of contemporary educational models in formal and non-formal areas of elementary education in the Costa Rican context. Our purpose is that students and teachers of the career program Pedagogía con énfasis en I y II ciclos de la Educación General Básica have an overview of the national, social, and educational reality in an attempt to involve them in applying pedagogical actions towards finding a solution to school dropouts at Escuela Finca Guararí, Heredia, Costa Rica. The essay describes the experience of teaching education students and their socio-educational action with the focus on the systematization of the experience in the initial stage of the project. Furthermore, the paper connects with emerging strategic knowledge areas at División de Educación Básica (DEB, such as social and community pedagogy in the context of the National University (UNA of Costa Rica. It takes over a route already traced at DEB, which proposes more flexible and alternative pedagogic formats to promote educational equity and diversity issues. The paper describes the project background and a theoretical framework, as well as aspects that have been shared by the protagonist actors along the process: students-teachers, host teachers, supervisor professors, school children, and their parents at Escuela Finca Guararí. Conclusions address main results and facts during 2016 in order to show the viability of the project, which is conducted from a public university. Finally, the article also

  4. Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages.

    Science.gov (United States)

    da Silva-Souza, Hercules Antônio; Lira, Maria Nathalia de; Costa-Junior, Helio Miranda; da Cruz, Cristiane Monteiro; Vasconcellos, Jorge Silvio Silva; Mendes, Anderson Nogueira; Pimenta-Reis, Gabriela; Alvarez, Cora Lilia; Faccioli, Lucia Helena; Serezani, Carlos Henrique; Schachter, Julieta; Persechini, Pedro Muanis

    2014-07-01

    We have previously described that arachidonic acid (AA)-5-lipoxygenase (5-LO) metabolism inhibitors such as NDGA and MK886, inhibit cell death by apoptosis, but not by necrosis, induced by extracellular ATP (ATPe) binding to P2X7 receptors in macrophages. ATPe binding to P2X7 also induces large cationic and anionic organic molecules uptake in these cells, a process that involves at least two distinct transport mechanisms: one for cations and another for anions. Here we show that inhibitors of the AA-5-LO pathway do not inhibit P2X7 receptors, as judged by the maintenance of the ATPe-induced uptake of fluorescent anionic dyes. In addition, we describe two new transport phenomena induced by these inhibitors in macrophages: a cation-selective uptake of fluorescent dyes and the release of ATP. The cation uptake requires secreted ATPe, but, differently from the P2X7/ATPe-induced phenomena, it is also present in macrophages derived from mice deficient in the P2X7 gene. Inhibitors of phospholipase A2 and of the AA-cyclooxygenase pathway did not induce the cation uptake. The uptake of non-organic cations was investigated by measuring the free intracellular Ca(2+) concentration ([Ca(2+)]i) by Fura-2 fluorescence. NDGA, but not MK886, induced an increase in [Ca(2+)]i. Chelating Ca(2+) ions in the extracellular medium suppressed the intracellular Ca(2+) signal without interfering in the uptake of cationic dyes. We conclude that inhibitors of the AA-5-LO pathway do not block P2X7 receptors, trigger the release of ATP, and induce an ATP-dependent uptake of organic cations by a Ca(2+)- and P2X7-independent transport mechanism in macrophages. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Direct ATP photolabeling of Escherichia coli recA proteins: identification of regions required for ATP binding

    International Nuclear Information System (INIS)

    Banks, G.R.; Sedgwick, S.G.

    1986-01-01

    When the Escherichia coli RecA protein is UV irradiated in the presence of [alpha- 32 P]ATP, a labeled protein--ATP adduct is formed. All the experimental evidence indicates that, in forming such an adduct, the ATP becomes specifically immobilized in the catalytically relevant ATP binding site. The adduct can also be identified after irradiation of E. coli cell lysates in a similar manner. This direct ATP photolabeling of RecA proteins has been used to identify regions of the polypeptide chain involved in the binding of ATP. The photolabeling of a RecA protein that lacks wild-type carboxy-terminal amino acids is not detectable. A RecA protein in which the amino-terminal sequence NH2-Ala-Ile-Asp-Glu-Asn- is replaced by NH2-Thr-Met-Ile-Thr-Asn-Ser-Ser-Ser- is only about 5% as efficiently photolabeled as the wild-type protein. Both of these RecA protein constructions, however, contain all the elements previously implicated, directly or indirectly, in the binding of ATP. ATP-photolabeled RecA protein has also been chemically cleaved at specific amino acids in order to identify regions of the polypeptide chain to which the nucleotide becomes covalently photolinked. The evidence is consistent with a region comprising amino acids 116-170. Thus, this work and that of others suggest that several disparate regions of the unfolded polypeptide chain may combine to form the ATP binding site upon protein folding or may influence binding through long-range effects

  6. 76 FR 30182 - Notice of Submission of Proposed Information Collection to OMB Section 5(h) Homeownership Program...

    Science.gov (United States)

    2011-05-24

    ... Its Proposed Use: Public Housing Agencies (PHAs) maintain sales and financial records of their plan... comments on the subject proposal. Public Housing Agencies (PHAs) maintain sales and financial records of their plan. Residents may apply to PHAs to purchase units. DATES: Comments Due Date: June 23, 2011...

  7. 76 FR 47180 - Pick-Sloan Missouri Basin Program-Eastern Division-2021 Power Marketing Initiative Proposal

    Science.gov (United States)

    2011-08-04

    ... marketing plan principles. The comment period for the proposed 2021 PMI ended on May 4, 2011. Western... customers the opportunity to review current marketing plan principles and provide informal input to Western... Division--2021 Power Marketing Initiative Proposal AGENCY: Western Area Power Administration, DOE. ACTION...

  8. 75 FR 62635 - Proposed Information Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program...

    Science.gov (United States)

    2010-10-12

    ... Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program) Activity: Comment Request... determine patients' satisfaction with services provided by or through the Michael E. DeBakey Home Care...: Patient Satisfaction Survey Michael E. DeBakey Home Care Program, VA Form 10-0476. OMB Control Number...

  9. 76 FR 624 - Proposed Information Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program...

    Science.gov (United States)

    2011-01-05

    ... Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program) Activity: Comment Request... satisfaction with the quality of services/care provided by home care program staff. An agency may not conduct... Form 10-0476).'' SUPPLEMENTARY INFORMATION: Title: Patient Satisfaction Survey Michael E. DeBakey Home...

  10. 77 FR 6585 - Proposed Information Collection Request (ICR) for the Impact Evaluation of the YouthBuild Program...

    Science.gov (United States)

    2012-02-08

    ... job characteristics? What are YouthBuild's impacts on crime and delinquency? What are the program's... (ICR) for the Impact Evaluation of the YouthBuild Program; New Collection AGENCY: Employment and... instruments are clearly understood, and the impact of collection requirements on respondents can be properly...

  11. 76 FR 27363 - Proposed Information Collection Request (ICR) for the Impact Evaluation of the YouthBuild Program...

    Science.gov (United States)

    2011-05-11

    ... characteristics? What are YouthBuild's impacts on crime and delinquency? What are the program's impacts on social... (ICR) for the Impact Evaluation of the YouthBuild Program; Comment Request AGENCY: Employment and..., collection instruments are clearly understood, and [[Page 27364

  12. 76 FR 8804 - 30-Day Notice of Proposed Information Collection: Form DS-3097, Exchange Visitor Program Annual...

    Science.gov (United States)

    2011-02-15

    ... DS-3097, Exchange Visitor Program Annual Report, OMB Control Number 1405-0151 ACTION: Notice of... Department of State has submitted the following information collection request to the Office of Management... Information Collection: Exchange Visitor Program Annual Report. OMB Control Number: 1405-0151. Type of Request...

  13. 75 FR 64775 - 60-Day Notice of Proposed Information Collection: Form DS-3097, Exchange Visitor Program Annual...

    Science.gov (United States)

    2010-10-20

    ... DS-3097, Exchange Visitor Program Annual Report, and OMB Control Number 1405- 0151 ACTION: Notice of request for public comments. SUMMARY: The Department of State is seeking Office of Management and Budget...: Exchange Visitor Program Annual Report. OMB Control Number: 1405-0151. Type of Request: Extension of a...

  14. 76 FR 77581 - 60-Day Notice of Proposed Information Collection: Form DS-3097, Exchange Visitor Program Annual...

    Science.gov (United States)

    2011-12-13

    ... DS-3097, Exchange Visitor Program Annual Report, and OMB Control Number 1405- 0151 ACTION: Notice of request for public comments. SUMMARY: The Department of State is seeking Office of Management and Budget...: Exchange Visitor Program Annual Report. OMB Control Number: 1405-0151. Type of Request: Extension of a...

  15. 77 FR 20687 - 30-Day Notice of Proposed Information Collection: Form DS-3097, Exchange Visitor Program Annual...

    Science.gov (United States)

    2012-04-05

    ...-3097, Exchange Visitor Program Annual Report, OMB Control Number 1405-0151 ACTION: Notice of request... Department of State has submitted the following information collection request to the Office of Management... Information Collection: Exchange Visitor Program Annual Report. OMB Control Number: 1405-0151. Type of Request...

  16. ( Atp9) gene between cytoplasmic male sterile line and its ...

    African Journals Online (AJOL)

    Administrator

    2011-09-07

    Sep 7, 2011 ... Soybean Research Institute of Nanjing Agricultural University, National Center for Soybean .... All these transgenic experiments confirmed the correlation ... editing of ATP synthase subunit 9 mRNA using wheat mitochondrial.

  17. Motor pathway excitability in ATP13A2 mutation carriers

    DEFF Research Database (Denmark)

    Zittel, S; Kroeger, J; van der Vegt, J P M

    2012-01-01

    OBJECTIVE: To describe excitability of motor pathways in Kufor-Rakeb syndrome (PARK9), an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration caused by a mutation in the ATP13A2 gene, using transcranial magnetic stimulation (TMS). METHODS: Five members of a Chilean family...... with an ATP13A2 mutation (one affected mutation carrier (MC) with a compound heterozygous mutation, 4 asymptomatic MC with a single heterozygous mutation) and 11 healthy subjects without mutations were studied. We measured motor evoked potentials (MEP), the contralateral silent period (cSP), short interval....... RESULTS: CSP duration was increased in the symptomatic ATP13A2 MC. The iSP measurements revealed increased interhemispheric inhibition in both the compound heterozygous and the heterozygous MC. CONCLUSION: A compound heterozygous mutation in the ATP13A2 gene is associated with increased intracortical...

  18. Highly divergent mitochondrial ATP synthase complexes in Tetrahymena thermophila.

    Directory of Open Access Journals (Sweden)

    Praveen Balabaskaran Nina

    2010-07-01

    Full Text Available The F-type ATP synthase complex is a rotary nano-motor driven by proton motive force to synthesize ATP. Its F(1 sector catalyzes ATP synthesis, whereas the F(o sector conducts the protons and provides a stator for the rotary action of the complex. Components of both F(1 and F(o sectors are highly conserved across prokaryotes and eukaryotes. Therefore, it was a surprise that genes encoding the a and b subunits as well as other components of the F(o sector were undetectable in the sequenced genomes of a variety of apicomplexan parasites. While the parasitic existence of these organisms could explain the apparent incomplete nature of ATP synthase in Apicomplexa, genes for these essential components were absent even in Tetrahymena thermophila, a free-living ciliate belonging to a sister clade of Apicomplexa, which demonstrates robust oxidative phosphorylation. This observation raises the possibility that the entire clade of Alveolata may have invented novel means to operate ATP synthase complexes. To assess this remarkable possibility, we have carried out an investigation of the ATP synthase from T. thermophila. Blue native polyacrylamide gel electrophoresis (BN-PAGE revealed the ATP synthase to be present as a large complex. Structural study based on single particle electron microscopy analysis suggested the complex to be a dimer with several unique structures including an unusually large domain on the intermembrane side of the ATP synthase and novel domains flanking the c subunit rings. The two monomers were in a parallel configuration rather than the angled configuration previously observed in other organisms. Proteomic analyses of well-resolved ATP synthase complexes from 2-D BN/BN-PAGE identified orthologs of seven canonical ATP synthase subunits, and at least 13 novel proteins that constitute subunits apparently limited to the ciliate lineage. A mitochondrially encoded protein, Ymf66, with predicted eight transmembrane domains could be a

  19. Role of ATP in the regulation of cholesterol biogenesis

    International Nuclear Information System (INIS)

    Subba Rao, G.; Ramasarma, T.

    1974-01-01

    Intraperitoneal administration of glucose (4oomg/rat) stimulated the biogenesis of sterols in starved rats while citrate or pyruvate (20mg/rat) did not have any effect. ATP (10mg/ rat) administered intraperitoneally stimulated the incorporation of acetate-1- 14 C into sterols but not of mevalonate-2- 14 C into sterols in starved rats. The results indicate that ATP may play a role in regulating cholesterol biogenesis and it is not acting merely as an energy source. (author)

  20. Predicting protein-ATP binding sites from primary sequence through fusing bi-profile sampling of multi-view features

    Directory of Open Access Journals (Sweden)

    Zhang Ya-Nan

    2012-05-01

    Full Text Available Abstract Background Adenosine-5′-triphosphate (ATP is one of multifunctional nucleotides and plays an important role in cell biology as a coenzyme interacting with proteins. Revealing the binding sites between protein and ATP is significantly important to understand the functionality of the proteins and the mechanisms of protein-ATP complex. Results In this paper, we propose a novel framework for predicting the proteins’ functional residues, through which they can bind with ATP molecules. The new prediction protocol is achieved by combination of sequence evolutional information and bi-profile sampling of multi-view sequential features and the sequence derived structural features. The hypothesis for this strategy is single-view feature can only represent partial target’s knowledge and multiple sources of descriptors can be complementary. Conclusions Prediction performances evaluated by both 5-fold and leave-one-out jackknife cross-validation tests on two benchmark datasets consisting of 168 and 227 non-homologous ATP binding proteins respectively demonstrate the efficacy of the proposed protocol. Our experimental results also reveal that the residue structural characteristics of real protein-ATP binding sites are significant different from those normal ones, for example the binding residues do not show high solvent accessibility propensities, and the bindings prefer to occur at the conjoint points between different secondary structure segments. Furthermore, results also show that performance is affected by the imbalanced training datasets by testing multiple ratios between positive and negative samples in the experiments. Increasing the dataset scale is also demonstrated useful for improving the prediction performances.

  1. Piezo1 regulates mechanotransductive release of ATP from human RBCs.

    Science.gov (United States)

    Cinar, Eyup; Zhou, Sitong; DeCourcey, James; Wang, Yixuan; Waugh, Richard E; Wan, Jiandi

    2015-09-22

    Piezo proteins (Piezo1 and Piezo2) are recently identified mechanically activated cation channels in eukaryotic cells and associated with physiological responses to touch, pressure, and stretch. In particular, human RBCs express Piezo1 on their membranes, and mutations of Piezo1 have been linked to hereditary xerocytosis. To date, however, physiological functions of Piezo1 on normal RBCs remain poorly understood. Here, we show that Piezo1 regulates mechanotransductive release of ATP from human RBCs by controlling the shear-induced calcium (Ca(2+)) influx. We find that, in human RBCs treated with Piezo1 inhibitors or having mutant Piezo1 channels, the amounts of shear-induced ATP release and Ca(2+) influx decrease significantly. Remarkably, a critical extracellular Ca(2+) concentration is required to trigger significant ATP release, but membrane-associated ATP pools in RBCs also contribute to the release of ATP. Our results show how Piezo1 channels are likely to function in normal RBCs and suggest a previously unidentified mechanotransductive pathway in ATP release. Thus, we anticipate that the study will impact broadly on the research of red cells, cellular mechanosensing, and clinical studies related to red cell disorders and vascular disease.

  2. Modification of synthesis nucleotides [γ-32P] ATP

    International Nuclear Information System (INIS)

    Wira Y Rahman; Endang Sarmini; Herlina; Triyanto; Hambali; Abdul Mutalib; Santi Nurbaiti

    2013-01-01

    In molecular biology, radionuclides in the form of radiolabeled compounds have been widely used as deoxyribonucleic acid (DNA) / ribonucleic acid (RNA) tracer in order to explore a wide range of physiological and pathological processes. One of such compounds is [γ- 32 P]-adenosine triphosphate {[γ- 32 P]-ATP} [γ- 32 P]-ATP which has been widely used in the biotechnology research. In order to support the biotechnology research in Indonesia in this project, [γ- 32 P]- ATP had been synthesized by enzymatic reactions with modifying the method of synthesis using the precursor DL-glyceraldehyde 3-phosphate, nucleotides Adenosine Diphosphate (ADP) and H 3 32 PO 4 and enzymes glyceraldehyde 3-phosphate dehydrogenase, 3-phosphoroglyceric phosphokinase and lactate dehydrogenase. The purification of the synthesized [γ- 32 P]-ATP, by using DEAE Sephadex column chromatography. The synthesis and purification process that had been performed were able in producing of [γ- 32 P]-ATP with radioactivity of 1,175 mCi and radiochemical purity of 99,49%.. Having successfully prepared the [γ- 32 P]-ATP and application, in the near future the Radioisotopes and Radiopharmaceuticals Centre is expected to be able in providing the above-mentioned radiolabeled nucleotide for biotechnology research in Indonesia. (author)

  3. 77 FR 28588 - Proposed Priorities-American Overseas Research Centers Program; CFDA Number 84.274A

    Science.gov (United States)

    2012-05-15

    .... scholars conducting overseas research that is vital to understanding the history, culture, economy... facilitate networking and collaborations via conferences, teaching opportunities for visiting faculty, and... and teaching at their home institutions. Proposed Priority 2--Projects that Provide Research, Teaching...

  4. Structural models of the human copper P-type ATPases ATP7A and ATP7B

    DEFF Research Database (Denmark)

    Gourdon, P.; Sitsel, Oleg; Karlsen, J.L.

    2012-01-01

    The human copper exporters ATP7A and ATP7B contain domains common to all P-type ATPases as well as class-specific features such as six sequential heavy-metal binding domains (HMBD1-HMBD6) and a type-specific constellation of transmembrane helices. Despite the medical significance of ATP7A and ATP7B......, allowing protein-specific properties to be addressed. Furthermore, the mapping of known disease-causing missense mutations indicates that among the heavy-metal binding domains, HMBD5 and HMBD6 are the most crucial for function, thus mimicking the single or dual HMBDs found in most copper-specific P-type...

  5. An ATP synthase harboring an atypical γ-subunit is involved in ATP synthesis in tomato fruit chromoplasts

    DEFF Research Database (Denmark)

    Pateraki, Irini; Renato, Marta; Azcõn-Bieto, Joaquín

    2013-01-01

    Chromoplasts are non-photosynthetic plastids specialized in the synthesis and accumulation of carotenoids. During fruit ripening, chloroplasts differentiate into photosynthetically inactive chromoplasts in a process characterized by the degradation of the thylakoid membranes, and by the active...... synthesis and accumulation of carotenoids. This transition renders chromoplasts unable to photochemically synthesize ATP, and therefore these organelles need to obtain the ATP required for anabolic processes through alternative sources. It is widely accepted that the ATP used for biosynthetic processes...... in non-photosynthetic plastids is imported from the cytosol or is obtained through glycolysis. In this work, however, we show that isolated tomato (Solanum lycopersicum) fruit chromoplasts are able to synthesize ATP de novo through a respiratory pathway using NADPH as an electron donor. We also report...

  6. Lysosomal Storage of Subunit c of Mitochondrial ATP Synthase in Brain-Specific Atp13a2-Deficient Mice.

    Science.gov (United States)

    Sato, Shigeto; Koike, Masato; Funayama, Manabu; Ezaki, Junji; Fukuda, Takahiro; Ueno, Takashi; Uchiyama, Yasuo; Hattori, Nobutaka

    2016-12-01

    Kufor-Rakeb syndrome (KRS) is an autosomal recessive form of early-onset parkinsonism linked to the PARK9 locus. The causative gene for KRS is Atp13a2, which encodes a lysosomal type 5 P-type ATPase. We recently showed that KRS/PARK9-linked mutations lead to several lysosomal alterations, including reduced proteolytic processing of cathepsin D in vitro. However, it remains unknown how deficiency of Atp13a2 is connected to lysosomal impairments. To address this issue, we analyzed brain tissues of Atp13a2 conditional-knockout mice, which exhibited characteristic features of neuronal ceroid lipofuscinosis, including accumulation of lipofuscin positive for subunit c of mitochondrial ATP synthase, suggesting that a common pathogenic mechanism underlies both neuronal ceroid lipofuscinosis and Parkinson disease. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Program proposed for dosimetric measures to be carried out during the start-up of the Juragua Nuclear Power Plant

    International Nuclear Information System (INIS)

    Romero Cabrera, J.L.

    1996-01-01

    The present measurement program fulfills two main tasks the first aimed at showing the staff permissible magnitudes of radiation doses and the second to the control of radiation protection and the gathering of necessary data for optimum radiation protection measures

  8. 75 FR 12325 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

    Science.gov (United States)

    2010-03-15

    ... LLC To Increase the Monthly ATP Fee for All Options Market Makers and To Reduce the Per- Contract... Exchange Commission (the ``Commission'') the proposed rule change as described in Items I, II, and III... Amex Trading Permit (``ATP'') for options Market Makers. Effective March 1, 2010 the Exchange proposes...

  9. 75 FR 10532 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

    Science.gov (United States)

    2010-03-08

    ... Commission (the ``Commission'') the proposed rule change as described in Items I, II, and III below, which... all similarly situated ATP Holders. 2. Statutory Basis The Exchange believes that the proposed rule... to all similarly situated ATP Holders. \\4\\ 15 U.S.C. 78f(b). \\5\\ 15 U.S.C. 78f(b)(4). B. Self...

  10. Calcium Co-regulates Oxidative Metabolism and ATP Synthase-dependent Respiration in Pancreatic Beta Cells

    Science.gov (United States)

    De Marchi, Umberto; Thevenet, Jonathan; Hermant, Aurelie; Dioum, Elhadji; Wiederkehr, Andreas

    2014-01-01

    Mitochondrial energy metabolism is essential for glucose-induced calcium signaling and, therefore, insulin granule exocytosis in pancreatic beta cells. Calcium signals are sensed by mitochondria acting in concert with mitochondrial substrates for the full activation of the organelle. Here we have studied glucose-induced calcium signaling and energy metabolism in INS-1E insulinoma cells and human islet beta cells. In insulin secreting cells a surprisingly large fraction of total respiration under resting conditions is ATP synthase-independent. We observe that ATP synthase-dependent respiration is markedly increased after glucose stimulation. Glucose also causes a very rapid elevation of oxidative metabolism as was followed by NAD(P)H autofluorescence. However, neither the rate of the glucose-induced increase nor the new steady-state NAD(P)H levels are significantly affected by calcium. Our findings challenge the current view, which has focused mainly on calcium-sensitive dehydrogenases as the target for the activation of mitochondrial energy metabolism. We propose a model of tight calcium-dependent regulation of oxidative metabolism and ATP synthase-dependent respiration in beta cell mitochondria. Coordinated activation of matrix dehydrogenases and respiratory chain activity by calcium allows the respiratory rate to change severalfold with only small or no alterations of the NAD(P)H/NAD(P)+ ratio. PMID:24554722

  11. Polyphosphate-dependent synthesis of ATP and ADP by the family-2 polyphosphate kinases in bacteria.

    Science.gov (United States)

    Nocek, Boguslaw; Kochinyan, Samvel; Proudfoot, Michael; Brown, Greg; Evdokimova, Elena; Osipiuk, Jerzy; Edwards, Aled M; Savchenko, Alexei; Joachimiak, Andrzej; Yakunin, Alexander F

    2008-11-18

    Inorganic polyphosphate (polyP) is a linear polymer of tens or hundreds of phosphate residues linked by high-energy bonds. It is found in all organisms and has been proposed to serve as an energy source in a pre-ATP world. This ubiquitous and abundant biopolymer plays numerous and vital roles in metabolism and regulation in prokaryotes and eukaryotes, but the underlying molecular mechanisms for most activities of polyP remain unknown. In prokaryotes, the synthesis and utilization of polyP are catalyzed by 2 families of polyP kinases, PPK1 and PPK2, and polyphosphatases. Here, we present structural and functional characterization of the PPK2 family. Proteins with a single PPK2 domain catalyze polyP-dependent phosphorylation of ADP to ATP, whereas proteins containing 2 fused PPK2 domains phosphorylate AMP to ADP. Crystal structures of 2 representative proteins, SMc02148 from Sinorhizobium meliloti and PA3455 from Pseudomonas aeruginosa, revealed a 3-layer alpha/beta/alpha sandwich fold with an alpha-helical lid similar to the structures of microbial thymidylate kinases, suggesting that these proteins share a common evolutionary origin and catalytic mechanism. Alanine replacement mutagenesis identified 9 conserved residues, which are required for activity and include the residues from both Walker A and B motifs and the lid. Thus, the PPK2s represent a molecular mechanism, which potentially allow bacteria to use polyP as an intracellular energy reserve for the generation of ATP and survival.

  12. A proposed emergency management program for acute care facilities in response to a highly virulent infectious disease.

    Science.gov (United States)

    Petinaux, Bruno; Ferguson, Brandy; Walker, Milena; Lee, Yeo-Jin; Little, Gary; Parenti, David; Simon, Gary

    2016-01-01

    To address the organizational complexities associated with a highly virulent infectious disease (HVID) hazard, such as Ebola Virus Disease (EVD), an acute care facility should institute an emergency management program rooted in the fundamentals of mitigation, preparedness, response, and recovery. This program must address all known facets of the care of a patient with HVID, from unannounced arrival to discharge. The implementation of such a program not only serves to mitigate the risks from an unrecognized exposure but also serves to prepare the organization and its staff to provide for a safe response, and ensure a full recovery. Much of this program is based on education, training, and infection control measures along with resourcing for appropriate personal protective equipment which is instrumental in ensuring an organized and safe response of the acute care facility in the service to the community. This emergency management program approach can serve as a model in the care of not only current HVIDs such as EVD but also future presentations in our healthcare setting.

  13. Sympathetic nerve-derived ATP regulates renal medullary blood flow via vasa recta pericytes

    Directory of Open Access Journals (Sweden)

    Scott S Wildman

    2013-10-01

    Full Text Available Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta, and therefore may be able to regulate medullary blood flow (MBF. Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesise that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is

  14. Hda monomerization by ADP binding promotes replicase clamp-mediated DnaA-ATP hydrolysis.

    Science.gov (United States)

    Su'etsugu, Masayuki; Nakamura, Kenta; Keyamura, Kenji; Kudo, Yuka; Katayama, Tsutomu

    2008-12-26

    ATP-DnaA is the initiator of chromosomal replication in Escherichia coli, and the activity of DnaA is regulated by the regulatory inactivation of the DnaA (RIDA) system. In this system, the Hda protein promotes DnaA-ATP hydrolysis to produce inactive ADP-DnaA in a mechanism that is mediated by the DNA-loaded form of the replicase sliding clamp. In this study, we first revealed that hda translation uses an unusual initiation codon, CUG, located downstream of the annotated initiation codon. The CUG initiation codon could be used for restricting the Hda level, as this initiation codon has a low translation efficiency, and the cellular Hda level is only approximately 100 molecules per cell. Hda translated using the correct reading frame was purified and found to have a high RIDA activity in vitro. Moreover, we found that Hda has a high affinity for ADP but not for other nucleotides, including ATP. ADP-Hda was active in the RIDA system in vitro and stable in a monomeric state, whereas apo-Hda formed inactive homomultimers. Both ADP-Hda and apo-Hda could form complexes with the DNA-loaded clamp; however, only ADP-Hda-DNA-clamp complexes were highly functional in the following interaction with DnaA. Formation of ADP-Hda was also observed in vivo, and mutant analysis suggested that ADP binding is crucial for cellular Hda activity. Thus, we propose that ADP is a crucial Hda ligand that promotes the activated conformation of the protein. ADP-dependent monomerization might enable the arginine finger of the Hda AAA+ domain to be accessible to ATP bound to the DnaA AAA+ domain.

  15. The National School Lunch Program: Ideas, proposals, policies, and politics shaping students' experiences with school lunch in the United States, 1946 - present

    OpenAIRE

    Gosliner, Wendi Anne

    2013-01-01

    AbstractThe National School Lunch Program:Ideas, proposals, policies, and politics shaping students' experiences with school lunch in the United States, 1946 - presentBy Wendi Anne GoslinerDoctor of Public HealthUniversity of California, BerkeleyProfessor Ann Keller, ChairOn an average school day in 2012, The National School Lunch Program (NSLP) supported the provision of lunch meals to almost 2/3 of school-age youth in the United States. Recent spikes in childhood obesity rates and the emerg...

  16. Proposal for the transmittal of data to LASL and the reporting of TRAC analyses for the multinational reflood experimental program

    International Nuclear Information System (INIS)

    Bleiweis, P.B.; Kirchner, W.L.; Sicilian, J.M.

    1979-04-01

    The proposed form of the digital tape containing the reduced experimental data from any of the 2D/3D facilities (CCTF, SCTF, UPTF, and possibly PKL Core-II) and the procedures which LASL will use in performing TRAC calculations and reporting results are described in this document

  17. 78 FR 55084 - Proposed Collection; 60-day Comment Request; Data Collection To Understand How NIH Programs Apply...

    Science.gov (United States)

    2013-09-09

    ... strategy management, total quality management, change management, organizational assessment and... periodic summaries of proposed projects to be submitted to the Office of Management and Budget (OMB) for... enhance the quality, utility, and clarity of the information to be collected; and (4) Ways to minimize the...

  18. 78 FR 44054 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program; Proposed Delay of...

    Science.gov (United States)

    2013-07-23

    ... delay the effective date of the 2011 Wage Rule to avoid the replacement of the wage provisions of the H... appropriated funds to implement, administer, or enforce the 2011 Wage Rule, the Department proposes to delay... subject of the 2011 Wage Rule, require the indefinite delay of the effective date of the 2011 Wage Rule...

  19. 77 FR 38375 - Advisory Circular (AC) 150/5345-53D, Airport Lighting Equipment Certification Program; Proposed...

    Science.gov (United States)

    2012-06-27

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Advisory Circular (AC) 150/5345-53D... Advisory Circular (AC) 150/5345-53D, Airport Lighting Equipment Certification Program, is being circulated... on a separate document and not embedded in the draft AC. Additionally, please provide justification...

  20. Mental Health Awareness and Services in Armenian-American Schools: A Grant Proposal for a Teacher Training Program

    Science.gov (United States)

    Tanielian, Aline Zarig

    2012-01-01

    School-based mental health programs in America provide students with psychological services that have been found to increase students' academic and social success and overall well-being. Furthermore, teacher involvement in students' psychological well-being via awareness, psychoeducation, and/or rendering help and resources has been found to be a…

  1. 78 FR 69171 - 60-Day Notice of Proposed Information Collection: Department of State Mentor Protégé Program...

    Science.gov (United States)

    2013-11-18

    ...: Department of State Mentor Prot[eacute]g[eacute] Program Application ACTION: Notice of request for public... [email protected] . SUPPLEMENTARY INFORMATION: Title of Information Collection: Department of State Mentor... planning to team together in an official mentor-prot[eacute]g[eacute] capacity to enhance the capabilities...

  2. Phylogenetic analysis of the thylakoid ATP/ADP carrier reveals new insights into its function restricted to green plants

    Directory of Open Access Journals (Sweden)

    Cornelia eSpetea

    2012-01-01

    Full Text Available ATP is the common energy currency of cellular metabolism in all living organisms. Most of them synthesize ATP in the cytosol or on the mitochondrial inner membrane, whereas land plants, algae and cyanobacteria also produce it on the thylakoid membrane during the light-dependent reactions of photosynthesis. From the site of synthesis, ATP is transported to the site of utilization via intracellular membranes transporters. One major type of ATP transporter is represented by the mitochondrial ADP/ATP carrier family. Here we review a recently characterized member, namely the thylakoid ATP/ADP carrier from Arabidopsis thaliana (AtTAAC. Thus far, no orthologues of this carrier have been characterized in other organisms, although similar sequences can be recognized in many sequenced genomes. Protein Sequence database searches and phylogenetic analyses indicate the absence of TAAC in cyanobacteria and its appearance early in the evolution of photosynthetic eukaryotes. The TAAC clade is composed of carriers found in land plants and some green algae, but no proteins from other photosynthetic taxa, such as red algae, brown algae and diatoms. This implies that TAAC-like sequences arose only once before the divergence of green algae and land plants. Based on these findings, it is proposed that TAAC may have evolved in response to the need of a new activity in higher photosynthetic eukaryotes. This activity may provide the energy to drive reactions during biogenesis and turnover of photosynthetic complexes, which are heterogenously distributed in a thylakoid membrane system composed of appressed and non-appressed regions.

  3. KREBER`S ADVENTURES: COMPUTER GAME ABOUT THE ATP FORMATION

    Directory of Open Access Journals (Sweden)

    F. J. Baêta

    2015-08-01

    Full Text Available Introduction: Biochemistry, as well as other subjects related to molecular area, have several abstract and difficult concepts to be understood, therefore, many educational innovations have been developed, highlighting the digital games. The digital games feature a playful and motivational character that encourages students during the concepts learning, with a different way to learning the concepts studied. Objectives: The objective of this study was the development of a computer game focused on the concepts of ATP formation, including the glycolytic pathway, Krebs cycle and Electron Transport Chain, as well as aspects related to the regulation, and evaluate the usability of it, as well as some evidence of its educational potential. Material and methods: The development of the game followed the following steps: definition of the subject; understanding of game developer (it was chosen the GameMaker; storyboard creation of the game; prototyping, implementation and usability testing. For the evaluation, inspection usability was performed (without involving end users and subsequently the cognitive route and the usability questionnaire (the latter two with students of the discipline of Biochemistry. Results: The game approached the energy metabolism in three phases: the glycolytic pathway, Krebs cycle and electron transport chain. Each phase has a different purpose, with some questions about the ways. To complete the game, you must correctly answer the questions, avoid the obstacles and achieve the goals of each phase. After usability testing, it found that users could, in a playful manner, actively interact with the content addressed and, through the difficulties presented in the game, had the opportunity to expand and review their knowledge. Conclusions: The game was identified as a motivating and innovative proposal for  teaching, and it had good usability for undergraduate students. The ludic worked as a pedagogical practice encourages student

  4. Synthesis and purification of [γP32]-ATP

    International Nuclear Information System (INIS)

    Kukuh, Ratnawati; Santoso, Daniel; Basri, T. Hasan; Natalia Adventini

    1995-01-01

    The synthesis of [γP 3 2]-ATP has been carried out using an enzymes procedure. The compound was formed by the phosphorylation of ADP during the enzymatic conversion of L-α-glycerol-phosphate to 3-phosphoglycerate. In the present study, lactatedehydrogenase and sodium pyruvat were used in order to maintain β-NAD + concentration and to push the reaction of glyceralaldehyde-3-phosphate dehydrogenase towards the formation of 1,3-diphosphoglycerate. L-α-glycerolphosphate was used as primary substrate, as it is more stable than DL-glyceraldehyde-3-phosphate. The enzymatic reaction was stopped by immersing the reaction vessel in boiling water for about 10 minutes. The labelled [γP 3 2]-ATP formed was separated by thin layer chromatography using PEI-cellulose and the spots of [γP 3 2]-ATP and inorganic P 3 2 residue located by autoradiography using X-ray film. The optimum time for the reaction at room temperature was 90 minutes with a labeling efficiency of 94.9 %. Purification of the [γP 3 2]-ATP by anion exchange chromatography using DEAE sephadex yielded a purity of more than 95%. The results showed that the labeled compound [γP 3 2]-ATP can be synthesized via an enzymatic process with a satisfactory yield. (author), 4 refs, 2 tabs, 2 figs

  5. CFTR mediates noradrenaline-induced ATP efflux from DRG neurons.

    Science.gov (United States)

    Kanno, Takeshi; Nishizaki, Tomoyuki

    2011-09-24

    In our earlier study, noradrenaline (NA) stimulated ATP release from dorsal root ganglion (DRG) neurons as mediated via β(3) adrenoceptors linked to G(s) protein involving protein kinase A (PKA) activation, to cause allodynia. The present study was conducted to understand how ATP is released from DRG neurons. In an outside-out patch-clamp configuration from acutely dissociated rat DRG neurons, single-channel currents, sensitive to the P2X receptor inhibitor PPADS, were evoked by approaching the patch-electrode tip close to a neuron, indicating that ATP is released from DRG neurons, to activate P2X receptor. NA increased the frequency of the single-channel events, but such NA effect was not found for DRG neurons transfected with the siRNA to silence the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the immunocytochemical study using acutely dissociated rat DRG cells, CFTR was expressed in neurons alone, but not satellite cells, fibroblasts, or Schwann cells. It is concluded from these results that CFTR mediates NA-induced ATP efflux from DRG neurons as an ATP channel.

  6. The U.S. Marine Corps Combined Action Program (CAP): A Proposed Alternative Strategy for the Vietnam War

    Science.gov (United States)

    2002-05-01

    Vietnamese men abstained from premarital sex, they openly practiced mutual masturbation . 62 In western culture, a man’s business was a man’s business, but... practice of integrating Marine with native forces marked the beginning of a nearly six year endeavor entitled the Combined Action Program or CAP. Embraced...chain of command. While the CAP platoons drew from infantry battalions primarily, their ties to them remained administrative and informal in practice

  7. The need of a weight management control program in judo: a proposal based on the successful case of wrestling.

    Science.gov (United States)

    Artioli, Guilherme G; Franchini, Emerson; Nicastro, Humberto; Sterkowicz, Stanislaw; Solis, Marina Y; Lancha, Antonio H

    2010-05-04

    Judo competitions are divided into weight classes. However, most athletes reduce their body weight in a few days before competition in order to obtain a competitive advantage over lighter opponents. To achieve fast weight reduction, athletes use a number of aggressive nutritional strategies so many of them place themselves at a high health-injury risk. In collegiate wrestling, a similar problem has been observed and three wrestlers died in 1997 due to rapid weight loss regimes. After these deaths, the National Collegiate Athletic Association had implemented a successful weight management program which was proven to improve weight management behavior. No similar program has ever been discussed by judo federations even though judo competitors present a comparable inappropriate pattern of weight control. In view of this, the basis for a weight control program is provided in this manuscript, as follows: competition should begin within 1 hour after weigh-in, at the latest; each athlete is allowed to be weighed-in only once; rapid weight loss as well as artificial rehydration (i.e., saline infusion) methods are prohibited during the entire competition day; athletes should pass the hydration test to get their weigh-in validated; an individual minimum competitive weight (male athletes competing at no less than 7% and females at no less than 12% of body fat) should be determined at the beginning of each season; athletes are not allowed to compete in any weight class that requires weight reductions greater than 1.5% of body weight per week. In parallel, educational programs should aim at increasing the athletes', coaches' and parents' awareness about the risks of aggressive nutritional strategies as well as healthier ways to properly manage body weight.

  8. ATP-induced changes in rat skeletal muscle contractility.

    Science.gov (United States)

    Gabdrakhmanov, A I; Khayrullin, A E; Grishin, C H; Ziganshin, A U

    2015-01-01

    Extracellular purine compounds, adenosine triphosphate (ATP) and adenosine, are involved in regulation of many cell functions, engaging in rapid and long-term cellular processes. The nucleotides, including ATP, exert their extracellular effects by influencing membrane P2 receptors. ATP outside of the cell rapidly is metabolized by the ecto-enzyme system to produce adenosine, which acts on separate adenosine (P1) receptors. Since adenosine and ATP often are functional antagonists, ATP degradation not only limits its effect, but also brings new ligand with different, often opposing, properties. Great variety and widespread of P2 and adenosine receptors in the body emphasize the important physiological and pathophysiological significance of these receptors, and make them very attractive as targets for potential drug action.The existence of several subtypes of P2 and adenosine receptors has been shown in the skeletal muscles. ATP as a co-transmitter is densely packed together with classical neurotransmitters in the presynaptic vesicles of vertebral motor units but until recently ATP was refused to have its own functional role there and was recognized only as a source of adenosine. However, on the eve of the third millennium there appeared data that ATP, released from the nerve ending and acting on presynaptic P2 receptors, suppresses subsequent quantum release of acetylcholine. The final product of its degradation, adenosine, performs a similar inhibitory effect acting on presynaptic adenosine receptors.Despite the fact that the mechanisms of presynaptic inhibitory action of ATP and other purines were studied earlier, the object of those studies was usually neuromuscular synapse of cold-blooded animals. The few studies, in which experiments were carried out on preparations of warm-blooded animals, described the basic effects of purines. These often were guided by the convenience of preparation of the synapses of the diaphragm. We think that those results cannot be

  9. ATP measurements for monitoring microbial drinking water quality

    DEFF Research Database (Denmark)

    Vang, Óluva Karin

    Current standard methods for surveillance of microbial drinking water quality are culture based, which are laborious and time-consuming, where results not are available before one to three days after sampling. This means that the water may have been consumed before results on deteriorated water....... The overall aim of this PhD study was to investigate various methodological features of the ATP assay for a potential implementation on a sensor platform as a real-time parameter for continuous on-line monitoring of microbial drinking water quality. Commercial reagents are commonly used to determine ATP......, microbial quality in distributed water, detection of aftergrowth, biofilm formation etc. This PhD project demonstrated that ATP levels are relatively low and fairly stable in drinking water without chlorine residual despite different sampling locations, different drinking water systems and time of year...

  10. Nisin depletes ATP and proton motive force in mycobacteria.

    Science.gov (United States)

    Chung, H J; Montville, T J; Chikindas, M L

    2000-12-01

    This study examined the inhibitory effect of nisin and its mode of action against Mycobacterium smegmatis, a non-pathogenic species of mycobacteria, and M. bovis-Bacill Carmette Guerin (BCG), a vaccine strain of pathogenic M. bovis. In agar diffusion assays, 2.5 mg ml(-1) nisin was required to inhibit M. bovis-BCG. Nisin caused a slow, gradual, time- and concentration-dependent decrease in internal ATP levels in M. bovis-BCG, but no ATP efflux was detected. In mycobacteria, nisin decreased both components of proton motive force (membrane potential, Delta Psi and Delta pH) in a time- and concentration-dependent manner. However, mycobacteria maintained their intracellular ATP levels during the initial time period of Delta Psi and Delta pH dissipation. These data suggest that the mechanism of nisin in mycobacteria is similar to that in food-borne pathogens.

  11. ATP Synthase, a Target for Dementia and Aging?

    Science.gov (United States)

    Larrick, James W; Larrick, Jasmine W; Mendelsohn, Andrew R

    2018-02-01

    Advancing age is the biggest risk factor for development for the major life-threatening diseases in industrialized nations accounting for >90% of deaths. Alzheimer's dementia (AD) is among the most devastating. Currently approved therapies fail to slow progression of the disease, providing only modest improvements in memory. Recently reported work describes mechanistic studies of J147, a promising therapeutic molecule previously shown to rescue the severe cognitive deficits exhibited by aged, transgenic AD mice. Apparently, J147 targets the mitochondrial alpha-F1-ATP synthase (ATP5A). Modest inhibition of the ATP synthase modulates intracellular calcium to activate AMP-activated protein kinase to inhibit mammalian target of rapamycin, a known mechanism of lifespan extension from worms to mammals.

  12. Diverse Functional Properties of Wilson Disease ATP7B Variants

    Science.gov (United States)

    Huster, Dominik; Kühne, Angelika; Bhattacharjee, Ashima; Raines, Lily; Jantsch, Vanessa; Noe, Johannes; Schirrmeister, Wiebke; Sommerer, Ines; Sabri, Osama; Berr, Frieder; Mössner, Joachim; Stieger, Bruno; Caca, Karel; Lutsenko, Svetlana

    2012-01-01

    BACKGROUND & AIMS Wilson disease is a severe disorder of copper metabolism caused by mutations in ATP7B, which encodes a copper-transporting adenosine triphosphatase. The disease presents with a variable phenotype that complicates the diagnostic process and treatment. Little is known about the mechanisms that contribute to the different phenotypes of the disease. METHODS We analyzed 28 variants of ATP7B from patients with Wilson disease that affected different functional domains; the gene products were expressed using the baculovirus expression system in Sf9 cells. Protein function was analyzed by measuring catalytic activity and copper (64Cu) transport into vesicles. We studied intracellular localization of variants of ATP7B that had measurable transport activities and were tagged with green fluorescent protein in mammalian cells using confocal laser scanning microscopy. RESULTS Properties of ATP7B variants with pathogenic amino-acid substitution varied greatly even if substitutions were in the same functional domain. Some variants had complete loss of catalytic and transport activity, whereas others lost transport activity but retained phosphor-intermediate formation or had partial losses of activity. In mammalian cells, transport-competent variants differed in stability and subcellular localization. CONCLUSIONS Variants in ATP7B associated with Wilson disease disrupt the protein’s transport activity, result in its mislocalization, and reduce its stability. Single assays are insufficient to accurately predict the effects of ATP7B variants the function of its product and development of Wilson disease. These findings will contribute to our understanding of genotype–phenotype correlation and mechanisms of disease pathogenesis. PMID:22240481

  13. Evaluation of the proposed pilot groundwater pump and treat demonstration for the Paducah Gaseous Diffusion Plant. Environmental Restoration Program

    Energy Technology Data Exchange (ETDEWEB)

    Bodenstein, G.W.; Bonczek, R.R.; Early, T.O.; Hale, T.B.; Huff, D.D.; Nickelson, M.D.; Rightmire, C.T.

    1992-11-01

    This report contains the evaluation and recommendations of a Groundwater Corrective Actions Review Team. The primary goal is to evaluate the technical merit of and the need to implement a proposed groundwater pump-and-treat demonstration project for the Northwest contaminant plume at Paducah, Kentucky. A key distinction recognized by the review team is that the proposed project is intended to be a full-scale hydraulic containment of contaminants migrating from the sources of the plume, not plume remediation. The key questions incorporated into this plan are whether (1) dense, nonaqueous-phase liquids (DNAPLS) are present in the Regional Gravel Aquifer (RGA) at the source of the plume and (2) {sup 99}Tc removal must be included as part of any groundwater treatment process. The first question cannot be answered until the contaminant sources are better defined; the second question requires further risk assessment and/or a policy decision by DOE. Technical evaluation by the review team suggests that the recommended course of action be to modify the proposed work plan to include accurate identification of the sources of contaminants and vertical distribution of contaminants within the Northwest plume before a decision is made on the preferred source-control option. If DNAPLs are not present in the RGA, removal or containment of the sources is recommended. If DNAPLs are present, then hydraulic containment will be required. Finally, the review team recognizes that it is necessary to initiate a more comprehensive analysis of sitewide remediation needs to create links between action taken for the Northwest plume and action taken for other contamination sites at PGPD.

  14. Medicare program; acquisition, protection and disclosure of utilization and quality control peer review organization (PRO) information--HCFA. Proposed rule.

    Science.gov (United States)

    1984-04-16

    This proposal would govern the acquisition, protection and disclosure of information obtained or generated by Utilization and Quality Control Peer Review Organizations (PROs). The Peer Review Improvement Act of 1982 authorizes PROs to acquire information necessary to fulfill their duties and functions, places limits on the disclosure of PRO information, and establishes penalties for unauthorized disclosure. These regulations would implement the PROs' statutory right of access to necessary information and set forth their responsibilities to assure that information once acquired is adequately safeguarded, and used only for proper purposes.

  15. A qualitative study of physicians' experiences with online learning in a masters degree program: benefits, challenges, and proposed solutions.

    Science.gov (United States)

    Dyrbye, Liselotte; Cumyn, Annabelle; Day, Hollis; Heflin, Mitchell

    2009-02-01

    In response to challenges to faculty development (e.g. time away from clinical, teaching, and other responsibilities; lack of mentors; and limited resources) online learning has become an important venue to provide education for physicians in curriculum development, instruction, assessment, evaluation, educational leadership, and education scholarship. Online learning however has its own unique challenges. Little is known about clinician-educators' experiences while participating in online programs and few studies have focused on their approaches to facilitate online learning. To explore the experiences of physicians pursuing a degree in higher education with online learning, including motivations for choosing this format, barriers encountered, and ideas for facilitating learning in the online environment. All students (n = 71) enrolled in online courses in the University of Illinois at Chicago Masters of Health Profession Education Program were surveyed in the spring of 2006. Responses were analysed using a qualitative approach. Of the 48 students who completed the survey (response rate 68%) 45 (94%) were physicians. The online format is convenient, flexible, and may be beneficial for learning. Students' responses raise issues inherent to online learning that must be addressed to optimize student-centered learning. These issues relate to: clarity of communication; difficulties in negotiating team work and in building relationships; technical demands; learning style preferences, and time commitment. Students provided recommendations for strategies to address these issues such as how to communicate clearly, facilitate teamwork, and optimize time management. Member checking supported the analysis. Online education programs meet the needs of physicians but have associated challenges. Further research is needed to explore the potential value of student suggested ways to optimize the online learning experience.

  16. Processing mechanics of alternate twist ply (ATP) yarn technology

    Science.gov (United States)

    Elkhamy, Donia Said

    Ply yarns are important in many textile manufacturing processes and various applications. The primary process used for producing ply yarns is cabling. The speed of cabling is limited to about 35m/min. With the world's increasing demands of ply yarn supply, cabling is incompatible with today's demand activated manufacturing strategies. The Alternate Twist Ply (ATP) yarn technology is a relatively new process for producing ply yarns with improved productivity and flexibility. This technology involves self plying of twisted singles yarn to produce ply yarn. The ATP process can run more than ten times faster than cabling. To implement the ATP process to produce ply yarns there are major quality issues; uniform Twist Profile and yarn Twist Efficiency. The goal of this thesis is to improve these issues through process modeling based on understanding the physics and processing mechanics of the ATP yarn system. In our study we determine the main parameters that control the yarn twist profile. Process modeling of the yarn twist across different process zones was done. A computational model was designed to predict the process parameters required to achieve a square wave twist profile. Twist efficiency, a measure of yarn torsional stability and bulk, is determined by the ratio of ply yarn twist to singles yarn twist. Response Surface Methodology was used to develop the processing window that can reproduce ATP yarns with high twist efficiency. Equilibrium conditions of tensions and torques acting on the yarns at the self ply point were analyzed and determined the pathway for achieving higher twist efficiency. Mechanistic modeling relating equilibrium conditions to the twist efficiency was developed. A static tester was designed to zoom into the self ply zone of the ATP yarn. A computer controlled, prototypic ATP machine was constructed and confirmed the mechanistic model results. Optimum parameters achieving maximum twist efficiency were determined in this study. The

  17. Study of anticipated impact on DOE programs from proposed reductions to the external occupational radiation exposure limit

    International Nuclear Information System (INIS)

    1978-01-01

    Many years of radiation exposure experience in all phases of nuclear energy applications were surveyed to evaluate the impact of reducing the present DOE limit of 5 rem/yr. Conclusions drawn are: (1) Reduction of the occupational exposure limit would result in significant increase in total accumulated exposure to the current radiation worker population and could require an increase in the work force with attending personnel and administrative problems. (2) Important programs/facilities would have to be abandoned. (3) Some engineering technology is not sufficiently developed to design or operate at the 0.5 rem/yr limit. (4) Exposure reduction to 2.5 rem/yr would significantly increase costs and would result in a small increase in total exposure to the work force. (5) Significant initial capital cost plus increased annual costs would result. (6) The major emphasis in controlling occupational exposure should be on continued work toward further reduction of total man-rem. This should involve continued development of ALAP programs along with improvements in dose measurement and recording methods, more sophisticated exposure records, and containment, handling and remote maintenance techniques. (7) Radiation protection practices at DOE facilities have maintained exposures of the bulk of the nuclear work force substantially below current limits for many years. (8) The current standards of 5 rem/yr is used only as a limit. For example, 97% of the employees receive less than 0.5 rem/yr

  18. ATP Release from Chemotherapy-Treated Dying Leukemia Cells Elicits an Immune Suppressive Effect by Increasing Regulatory T Cells and Tolerogenic Dendritic Cells.

    Science.gov (United States)

    Lecciso, Mariangela; Ocadlikova, Darina; Sangaletti, Sabina; Trabanelli, Sara; De Marchi, Elena; Orioli, Elisa; Pegoraro, Anna; Portararo, Paola; Jandus, Camilla; Bontadini, Andrea; Redavid, Annarita; Salvestrini, Valentina; Romero, Pedro; Colombo, Mario P; Di Virgilio, Francesco; Cavo, Michele; Adinolfi, Elena; Curti, Antonio

    2017-01-01

    Chemotherapy-induced immunogenic cell death can favor dendritic cell (DC) cross-priming of tumor-associated antigens for T cell activation thanks to the release of damage-associated molecular patterns, including ATP. Here, we tested the hypothesis that in acute myeloid leukemia (AML), ATP release, along with its well-known immune stimulatory effect, may also contribute to the generation of an immune suppressive microenvironment. In a cohort of AML patients, undergoing combined daunorubicin and cytarabine chemotherapy, a population of T regulatory cells (Tregs) with suppressive phenotype, expressing the immune checkpoint programmed cell death protein 1 (PD-1), was significantly increased. Moving from these results, initial in vitro data showed that daunorubicin was more effective than cytarabine in modulating DC function toward Tregs induction and such difference was correlated with the higher capacity of daunorubicin to induce ATP release from treated AML cells. DCs cultured with daunorubicin-treated AML cells upregulated indoleamine 2,3-dioxygenase 1 (IDO1), which induced anti-leukemia Tregs. These data were confirmed in vivo as daunorubicin-treated mice show an increase in extracellular ATP levels with increased number of Tregs, expressing PD-1 and IDO1 + CD39 + DCs. Notably, daunorubicin failed to induce Tregs and tolerogenic DCs in mice lacking the ATP receptor P2X7. Our data indicate that ATP release from chemotherapy-treated dying cells contributes to create an immune suppressive microenvironment in AML.

  19. ATP Release from Chemotherapy-Treated Dying Leukemia Cells Elicits an Immune Suppressive Effect by Increasing Regulatory T Cells and Tolerogenic Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Mariangela Lecciso

    2017-12-01

    Full Text Available Chemotherapy-induced immunogenic cell death can favor dendritic cell (DC cross-priming of tumor-associated antigens for T cell activation thanks to the release of damage-associated molecular patterns, including ATP. Here, we tested the hypothesis that in acute myeloid leukemia (AML, ATP release, along with its well-known immune stimulatory effect, may also contribute to the generation of an immune suppressive microenvironment. In a cohort of AML patients, undergoing combined daunorubicin and cytarabine chemotherapy, a population of T regulatory cells (Tregs with suppressive phenotype, expressing the immune checkpoint programmed cell death protein 1 (PD-1, was significantly increased. Moving from these results, initial in vitro data showed that daunorubicin was more effective than cytarabine in modulating DC function toward Tregs induction and such difference was correlated with the higher capacity of daunorubicin to induce ATP release from treated AML cells. DCs cultured with daunorubicin-treated AML cells upregulated indoleamine 2,3-dioxygenase 1 (IDO1, which induced anti-leukemia Tregs. These data were confirmed in vivo as daunorubicin-treated mice show an increase in extracellular ATP levels with increased number of Tregs, expressing PD-1 and IDO1+CD39+ DCs. Notably, daunorubicin failed to induce Tregs and tolerogenic DCs in mice lacking the ATP receptor P2X7. Our data indicate that ATP release from chemotherapy-treated dying cells contributes to create an immune suppressive microenvironment in AML.

  20. Effects of Irradiation on bacterial atp luminous intensity of cooled pork and chicken

    International Nuclear Information System (INIS)

    Ju Hua

    2010-01-01

    The effect of irradiation on cooled pork and chicken was detected with ATP luminous intensity method. The influences of other factors to ATP luminous intensity were also discussed. There was positive correlation between ATP standard concentration and ATP luminous intensity, and negative correlation between irradiation dosage and ATP luminous intensity. The trend of ATP luminous intensity of cooled pork and chicken after irradiation was inverse S, and the maximum ATP luminous intensity appeared at 6.0 kGy, and minimum at 4.0 and 8.0 kGy. Sterilized water and sterilized pork had no interference to ATP luminous intensity of the samples. There was significant positive correlation between E. coli 10003 concentration and ATP luminous intensity, the coefficient correlation was 0.9437. (authors)

  1. Analysis of Combined Data from Heterogeneous Study Designs: A Methodological Proposal from the Patient Navigation Research program

    Science.gov (United States)

    Roetzheim, Richard G.; Freund, Karen M.; Corle, Don K.; Murray, David M.; Snyder, Frederick R.; Kronman, Andrea C.; Jean-Pierre, Pascal; Raich, Peter C.; Holden, Alan E. C.; Darnell, Julie S.; Warren-Mears, Victoria; Patierno, Steven; Design, PNRP; Committee, Analysis

    2013-01-01

    Background The Patient Navigation Research Program (PNRP) is a cooperative effort of nine research projects, each employing its own unique study design. To evaluate projects such as PNRP, it is desirable to perform a pooled analysis to increase power relative to the individual projects. There is no agreed upon prospective methodology, however, for analyzing combined data arising from different study designs. Expert opinions were thus solicited from members of the PNRP Design and Analysis Committee Purpose To review possible methodologies for analyzing combined data arising from heterogeneous study designs. Methods The Design and Analysis Committee critically reviewed the pros and cons of five potential methods for analyzing combined PNRP project data. Conclusions were based on simple consensus. The five approaches reviewed included: 1) Analyzing and reporting each project separately, 2) Combining data from all projects and performing an individual-level analysis, 3) Pooling data from projects having similar study designs, 4) Analyzing pooled data using a prospective meta analytic technique, 5) Analyzing pooled data utilizing a novel simulated group randomized design. Results Methodologies varied in their ability to incorporate data from all PNRP projects, to appropriately account for differing study designs, and in their impact from differing project sample sizes. Limitations The conclusions reached were based on expert opinion and not derived from actual analyses performed. Conclusions The ability to analyze pooled data arising from differing study designs may provide pertinent information to inform programmatic, budgetary, and policy perspectives. Multi-site community-based research may not lend itself well to the more stringent explanatory and pragmatic standards of a randomized controlled trial design. Given our growing interest in community-based population research, the challenges inherent in the analysis of heterogeneous study design are likely to become

  2. ATP regeneration with enzymes of the alcohol fermentation pathway and kinases of yeast and its computer simulation

    Energy Technology Data Exchange (ETDEWEB)

    Asada, M; Shirai, Y; Nakanishi, K; Matsuno, R; Kimura, A; Kamikubo, T

    1981-08-01

    Enzymes of the alcohol fermentation pathway, adenosine kinase and adenylate kinase were extracted by incubating acetone-dried yeast cells with a simple reaction medium containing glucose, and subjected to gel filtration to remove the intermediates of alcohol fermentation formed during incubation. By using the enzyme systems as catalysts and glucose as an energy source, ATP was regenerated from adenosine. A minimum concentration of fructose 1,6-bisphosphate (FBP) of 7 mM or of ATP of 10 mM was necessary to initiate the alcohol fermentation; and concentrations of nucleotides changed abruptly with reaction time. These nonlinear phenomena might be due to action of FBPase and/or ATPase as well as the complex multienzyme systems. To understand the experimentally observed phenomena, a mathematical model of the reaction system was proposed which takes into account ATP regeneration. The calculated time-dependent concentrations of glucose, FBP, adenosine and nucleotides were in agreement with experimental values qualitatively as well as quantitatively. Moreover, the nonlinear phenomena, that is, the existence of threshold concentrations of FBP and ATP below which the reaction can not proceed and the steep changes of nucleotide concentrations were also accounted for. These results indicate that the model was quite suitable for this reaction system and useful for predicting the experimental results.

  3. Fast monitoring of indoor bioaerosol concentrations with ATP bioluminescence assay using an electrostatic rod-type sampler.

    Directory of Open Access Journals (Sweden)

    Ji-Woon Park

    Full Text Available A culture-based colony counting method is the most widely used analytical technique for monitoring bioaerosols in both indoor and outdoor environments. However, this method requires several days for colony formation. In this study, our goal was fast monitoring (Sampling: 3 min, Detection: < 1 min of indoor bioaerosol concentrations with ATP bioluminescence assay using a bioaerosol sampler. For this purpose, a novel hand-held electrostatic rod-type sampler (110 mm wide, 115 mm long, and 200 mm tall was developed and used with a commercial luminometer, which employs the Adenosine triphosphate (ATP bioluminescence method. The sampler consisted of a wire-rod type charger and a cylindrical collector, and was operated with an applied voltage of 4.5 kV and a sampling flow rate of 150.7 lpm. Its performance was tested using Staphylococcus epidermidis which was aerosolized with an atomizer. Bioaerosol concentrations were measured using ATP bioluminescence method with our sampler and compared with the culture-based method using Andersen cascade impactor under controlled laboratory conditions. Indoor bioaerosol concentrations were also measured using both methods in various indoor environments. A linear correlation was obtained between both methods in lab-tests and field-tests. Our proposed sampler with ATP bioluminescence method may be effective for fast monitoring of indoor bioaerosol concentrations.

  4. Increased degradation of ATP is driven by memory regulatory T cells in kidney transplantation tolerance.

    Science.gov (United States)

    Durand, Maxim; Dubois, Florian; Dejou, Cécile; Durand, Eugénie; Danger, Richard; Chesneau, Mélanie; Brosseau, Carole; Guerif, Pierrick; Soulillou, Jean-Paul; Degauque, Nicolas; Eliaou, Jean-François; Giral, Magali; Bonnefoy, Nathalie; Brouard, Sophie

    2018-05-01

    Regulatory T cells were recently proposed as the central actor in operational tolerance after renal transplantation. Tolerant patients harbor increased FoxP3hi memory Treg frequency and increased demethylation in the Foxp3 Treg-specific demethylated region when compared to stable kidney recipients and exhibit greater memory Treg suppressive capacities and higher expression of the ectonucleotidase CD39. However, in this particular and unique situation the mechanisms of action of Tregs were not identified. Thus, we analyzed the ability of memory Tregs to degrade extracellular ATP in tolerant patients, healthy volunteers, and patients with stable graft function under immunosuppression and determined the role of immunosuppressive drugs on this process. The conserved proportion of memory Tregs leads to the establishment of a pro-tolerogenic balance in operationally tolerant patients. Memory Tregs in tolerant patients display normal capacity to degrade extracellular ATP/ADP. In contrast, memory Tregs from patients with stable graft function do not have this ability. Finally, in vitro, immunosuppressive drugs may favor the lower proportion of memory Tregs in stable patients, but they have no effect on CD39-dependent ATP degradation and do not explain memory Treg lack of extracellular ATP/ADP degradation ability. Thus, intrinsic active regulatory mechanisms may act long after immunosuppressive drug arrest in operationally tolerant patients and may contribute to kidney allograft tolerance via the maintenance of CD39 Treg function. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  5. Two weeks of muscle immobilization impairs functional sympatholysis but increases exercise hyperemia and the vasodilatory responsiveness to infused ATP

    DEFF Research Database (Denmark)

    Mortensen, Stefan P; Mørkeberg, Jakob S; Thaning, Pia

    2012-01-01

    During exercise, contracting muscles can override sympathetic vasoconstrictor activity (functional sympatholysis). ATP and adenosine have been proposed to play a role in skeletal muscle blood flow regulation. However, little is known about the role of muscle training status on functional sympatho......During exercise, contracting muscles can override sympathetic vasoconstrictor activity (functional sympatholysis). ATP and adenosine have been proposed to play a role in skeletal muscle blood flow regulation. However, little is known about the role of muscle training status on functional....../min; P higher in the immobilized leg (2.9 ± 0.2 l/min; P .... Mean arterial pressure was lower during exercise with the trained leg compared with the immobilized leg (P higher after immobilization (3.9 ± 0.3 and 4.5 ± 0.6 l/min in the control and immobilized leg...

  6. Limitations of ATP as a measure of microbial biomass

    African Journals Online (AJOL)

    limits the use of ATP as a measure of microbial biomass. S. AIr. J. Zool. 1982, 17: 93 - 95. Beraming van die totale .... only micro-organisms present in the experimental culture, but these were later succeeded by a large ... a value of 49: I by the last day of the experiment. Estimates of the total living biomass of the heterotro-.

  7. Exon duplications in the ATP7A gene

    DEFF Research Database (Denmark)

    Mogensen, Mie; Skjørringe, Tina; Kodama, Hiroko

    2011-01-01

    the identified duplicated fragments originated from a single or from two different X-chromosomes, polymorphic markers located in the duplicated fragments were analyzed. RESULTS: Partial ATP7A gene duplication was identified in 20 unrelated patients including one patient with Occipital Horn Syndrome (OHS...

  8. Electrochemical Investigation of the Interaction between Catecholamines and ATP.

    Science.gov (United States)

    Taleat, Zahra; Estévez-Herrera, Judith; Machado, José D; Dunevall, Johan; Ewing, Andrew G; Borges, Ricardo

    2018-02-06

    The study of the colligative properties of adenosine 5'-triphosphate (ATP) and catecholamines has received the attention of scientists for decades, as they could explain the capabilities of secretory vesicles (SVs) to accumulate neurotransmitters. In this Article, we have applied electrochemical methods to detect such interactions in vitro, at the acidic pH of SVs (pH 5.5) and examined the effect of compounds having structural similarities that correlate with functional groups of ATP (adenosine, phosphoric acid and sodium phosphate salts) and catecholamines (catechol). Chronoamperometry and fast scan cyclic voltammetry (FSCV) provide evidence compatible with an interaction of the catechol and adenine rings. This interaction is also reinforced by an electrostatic interaction between the phosphate group of ATP and the protonated ammonium group of catecholamines. Furthermore, chronoamperometry data suggest that the presence of ATP subtlety reduces the apparent diffusion coefficient of epinephrine in aqueous media that adds an additional factor leading to a slower rate of catecholamine exocytosis. This adds another plausible mechanism to regulate individual exocytosis events to alter communication.

  9. Supplementary data: Novel mutation in ATP-binding domain of ...

    Indian Academy of Sciences (India)

    Novel mutation in ATP-binding domain of ABCD1 gene in adrenoleucodystrophy. Neeraj Kumar, Krishna K. Taneja, Atul Kumar, Deepti Nayar, Bhupesh Taneja, Satindra Aneja,. Madhuri Behari, Veena Kalra and Surendra K. Bansal. J. Genet. 89, 473–477. Figure 1. Rmsd plot of native and Arg617Ser substituted models.

  10. 'Domino' systems biology and the 'A' of ATP.

    Science.gov (United States)

    Verma, Malkhey; Zakhartsev, Maksim; Reuss, Matthias; Westerhoff, Hans V

    2013-01-01

    We develop a strategic 'domino' approach that starts with one key feature of cell function and the main process providing for it, and then adds additional processes and components only as necessary to explain provoked experimental observations. The approach is here applied to the energy metabolism of yeast in a glucose limited chemostat, subjected to a sudden increase in glucose. The puzzles addressed include (i) the lack of increase in adenosine triphosphate (ATP) upon glucose addition, (ii) the lack of increase in adenosine diphosphate (ADP) when ATP is hydrolyzed, and (iii) the rapid disappearance of the 'A' (adenine) moiety of ATP. Neither the incorporation of nucleotides into new biomass, nor steady de novo synthesis of adenosine monophosphate (AMP) explains. Cycling of the 'A' moiety accelerates when the cell's energy state is endangered, another essential domino among the seven required for understanding of the experimental observations. This new domino analysis shows how strategic experimental design and observations in tandem with theory and modeling may identify and resolve important paradoxes. It also highlights the hitherto unexpected role of the 'A' component of ATP. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  11. Diversity and regulation of ATP sulfurylase in photosynthetic organisms

    Directory of Open Access Journals (Sweden)

    Laura ePrioretti

    2014-11-01

    Full Text Available ATP sulfurylase (ATPS catalyzes the first committed step in the sulfate assimilation pathway, the activation of sulfate prior to its reduction. ATPS has been studied in only a few model organisms and even in these cases to a much smaller extent than the sulfate reduction and cysteine synthesis enzymes. This is possibly because the latter were considered of greater regulatory importance for sulfate assimilation. Recent evidences (reported in this paper challenge this view and suggest that ATPSes may have a crucial regulatory role in sulfate assimilation, at least in algae.In the ensuing text, we summarize the current knowledge on ATPS, with special attention to the processes that control its activity and gene(s expression. Special attention is given to algae ATPSes. The focus on algae is the consequence of the fact that a comprehensive investigation of ATPSes revealed that the algal enzymes, especially those that are most likely involved in the pathway of sulfate reduction to cysteine, possess features that are not present in other organisms. For instance, algae ATPSes show a great diversity of isoforms and a high content of cysteine residues, whose positions are often conserved. It is interesting that, at least with respect to the number of cysteines, the ATPSes of eukaryotic algae are closer to the marine cyanobacteria of the genera Synechococcus and Prochlorococcus and are more distant from freshwater cyanobacteria. These characteristics might have evolved in parallel with the radiation of algae in the oceans and the increase of sulfate concentration in seawater.

  12. ATP stimulates calcium influx in primary astrocyte cultures

    International Nuclear Information System (INIS)

    Neary, J.T.; van Breemen, C.; Forster, E.; Norenberg, L.O.; Norenberg, M.D.

    1988-01-01

    The effect of ATP and other purines on 45 Ca uptake was studied in primary cultures of rat astrocytes. Treatment of the cells with ATP for 1 to 30 min brought about an increase in cellular 45 Ca. Stimulation of calcium influx by ATP was investigated using a 90 sec exposure to 45 Ca and over a concentration range of 0.1 nM to 3 mM; a biphasic dose-response curve was obtained with EC50 values of 0.3 nM and 9 uM, indicating the presence of low and high affinity purinergic binding sites. Similar levels of 45 Ca influx at 90 sec were observed with ATP, ADP and adenosine (all at 100 uM). Prior treatment of the cultures with LaCl3 blocked the purine-induced 45 Ca influx. These findings indicate that one pathway for calcium entry in astrocytes involves purinergic receptor-operated, calcium channels

  13. ATP Production in Chlamydomonas reinhardtii Flagella by Glycolytic Enzymes

    DEFF Research Database (Denmark)

    Mitchell, Beth F; Pedersen, Lotte B; Feely, Michael

    2005-01-01

    reside in the detergent-soluble (membrane + matrix) compartments. We further show that axonemal enolase is a subunit of the CPC1 central pair complex and that reduced flagellar enolase levels in the cpc1 mutant correlate with the reduced flagellar ATP concentrations and reduced in vivo beat frequencies...

  14. Educational Philosophies Adhered by Filipino Preservice Teachers: Basis for Proposing Initiatives for 21st Century Teacher Education Preparation Program

    Directory of Open Access Journals (Sweden)

    Gilbert C. Magulod Jr.

    2017-02-01

    Full Text Available The study endeavoured to ascertain the educational philosophies adhered by Filipino preservice teachers. Descriptive survey research method was employed. The participants of the study were the 76 fourth year Bachelor in Elementary Education (BEED and Bachelor in Secondary Education (BSED of the College of Teacher Education in one state university in the Philippines. Data were gathered with the use of standardized research tool. Research findings showed that the Filipino preservice teachers espoused a very high adherence to progressivism educational philosophy and high orientation to existentialism and reconstructionism. They also showed a moderate adherence to perennialism and existentialism philosophies. These imply that they espoused a high student-centred teaching belief with partial acceptance to teacher-centred teaching belief. Test of difference and Post hoc analysis revealed that course, residence and scholastic standing in high school spelled differences on the educational philosophies of the Filipino preservice teachers. Findings of the study present initiatives for 21st century teacher education preparation program.

  15. Study of anticipated impact on DOE programs from proposed reductions to the external occupational radiation exposure limit

    International Nuclear Information System (INIS)

    1981-02-01

    A study of the impact of reducing the occupational radiation exposure limit from 5 rem/yr to 2.5, 1.0 and 0.5 rem/yr, respectively produced the following conclusions: reduction of the occupational exposure limit would result in significant increase in total accumulated exposure to the current radiation worker population and could require an increase in the work force; important programs would have to be abandoned at a planned exposure limit of 0.5 rem/yr; some engineering technology is not sufficiently developed to design or operate at the 0.5 rem/yr limit; even a factor of 2 reduction (2.5 rem/yr) would significantly increase costs and would result in an increase in total exposure to the work force; in addition to a significant one-time initial capital cost resulting from a 0.5 rem/yr limit, there would be a significant increase in annual costs; the major emphasis in controlling occupational exposure should be on further reduction of total man-rem; and current standards are used only as a limit. For example, 97% of the employees receive less than 0.5 rem/yr

  16. Death Valley Lower Carbonate Aquifer Monitoring Program Wells Down gradient of the Proposed Yucca Mountain Nuclear Waste Repository

    International Nuclear Information System (INIS)

    Inyo County

    2006-01-01

    Inyo County has participated in oversight activities associated with the Yucca Mountain Nuclear Waste Repository since 1987. The overall goal of these studies are the evaluation of far-field issues related to potential transport, by ground water, or radionuclides into Inyo County, including Death Valley, and the evaluation of a connection between the Lower Carbonate Aquifer (LCA) and the biosphere. Our oversight and completed Cooperative Agreement research, and a number of other investigators research indicate that there is groundwater flow between the alluvial and carbonate aquifers both at Yucca Mountain and in Inyo County. In addition to the potential of radionuclide transport through the LCA, Czarnecki (1997), with the US Geological Survey, research indicate potential radionuclide transport through the shallower Tertiary-age aquifer materials with ultimate discharge into the Franklin Lake Playa in Inyo County. The specific purpose of this Cooperative Agreement drilling program was to acquire geological, subsurface geology, and hydrologic data to: (1) establish the existence of inter-basin flow between the Amargosa Basin and Death Valley Basin; (2) characterize groundwater flow paths in the LCA through Southern Funeral Mountain Range, and (3) Evaluation the hydraulic connection between the Yucca Mountain repository and the major springs in Death Valley through the LCA

  17. Renewable energy for America`s cities: Advanced Community Energy Systems Proposed Research, Development and Demonstration Program

    Energy Technology Data Exchange (ETDEWEB)

    Gleason, T.C.J.

    1993-01-01

    The first purpose of this paper is to describe ACES technologies and their potential impact on the environment, the US energy supply system and economy. The second purpose is to recommend an R,D&D program to the US Department of Energy which has as its goal the rapid development of the most promising of the new technologies. ACES supply thermal energy to groups of buildings, communities and cities in the form of hot or chilled water for building space heating, domestic hot water or air conditioning. The energy is supplied via a network of insulated, underground pipes linking central sources of supply with buildings. ACES, by definition, employ very high energy efficiency conversion technologies such as cogeneration, heat pumps, and heat activated chillers. These systems also use renewable energy sources such as solar energy, winter cold, wind, and surface and subsurface warm and cold waters. ACES compose a new generation of community-scale building heating and air conditioning supply technologies. These new systems can effect a rapid and economical conversion of existing cities to energy supply by very efficient energy conversion systems and renewable energy systems. ACES technologies are the most promising near term means by which cities can make the transition from our present damaging dependence on fossil fuel supply systems to an economically and environmentally sustainable reliance on very high efficiency and renewable energy supply systems. When fully developed to serve an urban area, ACES will constitute a new utility system which can attain a level of energy efficiency, economy and reliance on renewable energy sources not possible with currently available energy supply systems.

  18. Renewable energy for America's cities: Advanced Community Energy Systems Proposed Research, Development and Demonstration Program

    Energy Technology Data Exchange (ETDEWEB)

    Gleason, T.C.J.

    1993-01-01

    The first purpose of this paper is to describe ACES technologies and their potential impact on the environment, the US energy supply system and economy. The second purpose is to recommend an R,D D program to the US Department of Energy which has as its goal the rapid development of the most promising of the new technologies. ACES supply thermal energy to groups of buildings, communities and cities in the form of hot or chilled water for building space heating, domestic hot water or air conditioning. The energy is supplied via a network of insulated, underground pipes linking central sources of supply with buildings. ACES, by definition, employ very high energy efficiency conversion technologies such as cogeneration, heat pumps, and heat activated chillers. These systems also use renewable energy sources such as solar energy, winter cold, wind, and surface and subsurface warm and cold waters. ACES compose a new generation of community-scale building heating and air conditioning supply technologies. These new systems can effect a rapid and economical conversion of existing cities to energy supply by very efficient energy conversion systems and renewable energy systems. ACES technologies are the most promising near term means by which cities can make the transition from our present damaging dependence on fossil fuel supply systems to an economically and environmentally sustainable reliance on very high efficiency and renewable energy supply systems. When fully developed to serve an urban area, ACES will constitute a new utility system which can attain a level of energy efficiency, economy and reliance on renewable energy sources not possible with currently available energy supply systems.

  19. Evidence that Na+/H+ exchanger 1 is an ATP-binding protein.

    Science.gov (United States)

    Shimada-Shimizu, Naoko; Hisamitsu, Takashi; Nakamura, Tomoe Y; Wakabayashi, Shigeo

    2013-03-01

    Na(+)/H(+) exchanger (NHE) 1 is a member of the solute carrier superfamily, which regulates intracellular ionic homeostasis. NHE1 is known to require cellular ATP for its activity, despite there being no requirement for energy input from ATP hydrolysis. In this study, we investigated whether NHE1 is an ATP-binding protein. We designed a baculovirus vector carrying both epitope-tagged NHE1 and its cytosolic subunit CHP1, and expressed the functional NHE1-CHP1 complex on the surface of Sf9 insect cells. Using the purified complex protein consisting of NHE1 and CHP1 from Sf9 cells, we examined a photoaffinity labeling reaction with 8-azido-ATP-biotin. UV irradiation promoted the incorporation of 8-azido-ATP into NHE1, but not into CHP1, with an apparent Kd of 29.1 µM in the presence of Mg(2+). The nonlabeled nucleotides ATP, GTP, TTP and CTP all inhibited this crosslinking. However, ATP had the strongest inhibitory effect, with an apparent inhibition constant (IC50) for ATP of 2.2 mM, close to the ATP concentration giving the half-maximal activation of NHE1 activity. Importantly, crosslinking was more strongly inhibited by ATP than by ADP, suggesting that ATP is dissociated from NHE1 upon ATP hydrolysis. Limited proteolysis with thrombin and deletion mutant analysis revealed that the 8-azido-ATP-binding site is within the C-terminal cytoplasmic domain of NHE1. Equilibrium dialysis with NHE1-derived peptides provided evidence that ATP directly binds to the proximal cytoplasmic region (Gly542-Pro598), which is critical for ATP-dependent regulation of NHE1. These findings suggest that NHE1 is an ATP-binding transporter. Thus, ATP may serve as a direct activator of NHE1. © 2013 The Authors Journal compilation © 2013 FEBS.

  20. How Native and Alien Metal Cations Bind ATP: Implications for Lithium as a Therapeutic Agent

    Science.gov (United States)

    Dudev, Todor; Grauffel, Cédric; Lim, Carmay

    2017-02-01

    Adenosine triphosphate (ATP), the major energy currency of the cell, exists in solution mostly as ATP-Mg. Recent experiments suggest that Mg2+ interacts with the highly charged ATP triphosphate group and Li+ can co-bind with the native Mg2+ to form ATP-Mg-Li and modulate the neuronal purine receptor response. However, it is unclear how the negatively charged ATP triphosphate group binds Mg2+ and Li+ (i.e. which phosphate group(s) bind Mg2+/Li+) and how the ATP solution conformation depends on the type of metal cation and the metal-binding mode. Here, we reveal the preferred ATP-binding mode of Mg2+/Li+ alone and combined: Mg2+ prefers to bind ATP tridentately to each of the three phosphate groups, but Li+ prefers to bind bidentately to the terminal two phosphates. We show that the solution ATP conformation depends on the cation and its binding site/mode, but it does not change significantly when Li+ binds to Mg2+-loaded ATP. Hence, ATP-Mg-Li, like Mg2+-ATP, can fit in the ATP-binding site of the host enzyme/receptor, activating specific signaling pathways.

  1. Structure of the oxalate-ATP complex with pyruvate kinase: ATP as a bridging ligand for the two divalent cations

    International Nuclear Information System (INIS)

    Lodato, D.T.; Reed, G.H.

    1987-01-01

    The 2 equiv of divalent cation that are required cofactors for pyruvate kinase reside in sites of different affinities for different species of cation. The intrinsic selectivity of the protein-based site for Mn(II) and of the nucleotide-based site for Mg(II) has been exploited in electron paramagnetic resonance (EOR) investigations of ligands for Mn(II) at the protein-based site. Oxalate, a structural analogue of the enolate of pyruvate, has been used as a surrogate for the reactive form of pyruvate in complexes with enzyme, Mn(II), Mg(II), and ATP. Superhyperfine coupling between the unpaired electron spin of Mn(II) and the nuclear spin of 17 O, specifically incorporated into oxalate, shows that oxalate is bound at the active site as a bidentate chelate with Mn(II). Coordination of the γ-phosphate of ATP to this same Mn(II) center is revealed by observation of superhyperfine coupling from 17 O regiospecifically incorporated into the γ-phosphate group of ATP. By contrast, 17 O in the α-phosphate or in the β-phosphate groups of ATP does not influence the spectrum. Experiments in 17 O-enriched water show that there is also a single water ligand bound to the Mn(II). These data indicate that ATP bridges Mn(II) and Mg(II) at the active site. A close spacing of the two divalent cations is also evident from the occurrence of magnetic interactions for complexes in which 2 equiv of Mn(II) are present at the active site. The structure for the enzyme-Mn(II)-oxalate-Mg(II)-ATP complex suggests a scheme for the normal reverse reaction of pyruvate kinase in which the divalent cation at the protein-based site activates the keto acid substrate through chelation and promotes phospho transfer by simultaneous coordination to the enolate oxygen and to a pendant oxygen from the γ-phosphate of ATP

  2. Loss of the gene for the alpha subunit of ATP synthase (ATP5A1) from the W chromosome in the African grey parrot (Psittacus erithacus).

    Science.gov (United States)

    de Kloet, S R

    2001-08-01

    This study describes the results of an analysis using Southern blotting, the polymerase chain reaction, and sequencing which shows that the African grey parrot (Psittacus erithacus) lacks the W-chromosomal gene for the alpha subunit of mitochondrial ATP synthase (ATP5A1W). Additional evidence shows that in other psittacines a fragment of the ATP5A1W gene contains five times as many nonsynonymous nucleotide replacements as the homologous fragment of the Z gene. Therefore, whereas in these other psittacines the corresponding ATP5A1Z protein fragment is highly conserved and varies by only a few, moderately conservative amino acid substitutions, the homologous ATP5A1W fragments contain a considerable number of, sometimes highly nonconservative, amino acid replacements. In one of these species, the ringneck parakeet (Psittacula krameri), the ATP5A1W gene is present in an inactive form because of the presence of a nonsense codon. Other changes, possibly leading to an inactive ATP5A1W gene product, involve the substitution of arginine residues by cysteine in the ATP5A1W protein of the mitred conure (Aratinga mitrata) and the blue and gold macaw (Ara ararauna). The data suggest also that although the divergence of the psittacine ATP5A1W and ATP5A1Z genes preceded the origin of the psittacidae, this divergence occurred independently of a similar process in the myna (Gracula religiosa), the outgroup used in this study.

  3. Proposal of a monitoring program of occupational exposure by incorporation of radioactive material for nuclear medicine services in the Caja Costarricense del Seguro Social

    International Nuclear Information System (INIS)

    Badilla Segura, Mirta

    2013-01-01

    A monitoring program of the occupational exposure by incorporation of radioactive material is proposed. Nuclear medicine services of the Caja Costarricense del Seguro Social (CCSS) are evaluated. The monitoring program is based on the provisions of the International Atomic Energy Agency and of study of nuclear medicine services of the CCSS. Radionuclides are determined for monitoring of the occupational exposure, according to the radioactive material that is worked in nuclear medicine services of the CCSS. The appropriate and alternative techniques are established for the monitoring of the occupational exposure by incorporation of radioactive material, depending on the type of radionuclide that is worked in nuclear medicine services. The worker occupationally exposed (TOE) should be subject of monitoring and how often should be realized the monitoring of the occupational exposure. The monitoring of the radiation by radioactive material must be applied to personnel working in radiopharmacies and the worker has carried out therapeutic procedures for handling of significant amounts of 13 1 I. The calculation of the committed effective dose is proposed by incorporation of radioactive material with the TOE [es

  4. Mechanical Control of ATP Synthase Function: Activation Energy Difference between Tight and Loose Binding Sites

    KAUST Repository

    Beke-Somfai, Tamás; Lincoln, Per; Nordén, Bengt

    2010-01-01

    Despite exhaustive chemical and crystal structure studies, the mechanistic details of how FoF1-ATP synthase can convert mechanical energy to chemical, producing ATP, are still not fully understood. On the basis of quantum mechanical calculations

  5. Metabolomic Analysis of Differential Changes in Metabolites during ATP Oscillations in Chondrogenesis

    Directory of Open Access Journals (Sweden)

    Hyuck Joon Kwon

    2013-01-01

    Full Text Available Prechondrogenic condensation is a critical step for skeletal pattern formation. Recent studies reported that ATP oscillations play an essential role in prechondrogenic condensation. However, the molecular mechanism to underlie ATP oscillations remains poorly understood. In the present study, it was investigated how changes in metabolites are implicated in ATP oscillations during chondrogenesis by using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS. CE-TOF-MS detected 93 cationic and 109 anionic compounds derived from known metabolic pathways. 15 cationic and 18 anionic compounds revealed significant change between peak and trough of ATP oscillations. These results implicate that glycolysis, mitochondrial respiration and uronic acid pathway oscillate in phase with ATP oscillations, while PPRP and nucleotides synthesis pathways oscillate in antiphase with ATP oscillations. This suggests that the ATP-producing glycolysis and mitochondrial respiration oscillate in antiphase with the ATP-consuming PPRP/nucleotide synthesis pathway during chondrogenesis.

  6. Agrobacterium VirB10, an ATP energy sensor required for type IV secretion.

    Science.gov (United States)

    Cascales, Eric; Christie, Peter J

    2004-12-07

    Bacteria use type IV secretion systems (T4SS) to translocate DNA and protein substrates to target cells of phylogenetically diverse taxa. Recently, by use of an assay termed transfer DNA immunoprecipitation (TrIP), we described the translocation route for a DNA substrate [T-DNA, portion of the Ti (tumor-inducing) plasmid that is transferred to plant cells] of the Agrobacterium tumefaciens VirB/D4 T4SS in terms of a series of temporally and spatially ordered substrate contacts with subunits of the secretion channel. Here, we report that the bitopic inner membrane protein VirB10 undergoes a structural transition in response to ATP utilization by the VirD4 and VirB11 ATP-binding subunits, as monitored by protease susceptibility. VirB10 interacts with inner membrane VirD4 independently of cellular energetic status, whereas the energy-induced conformational change is required for VirB10 complex formation with an outer membrane-associated heterodimer of VirB7 lipoprotein and VirB9, as shown by coimmunoprecipitation. Under these conditions, the T-DNA substrate is delivered from the inner membrane channel components VirB6 and VirB8 to periplasmic and outer membrane-associated VirB2 pilin and VirB9. We propose that VirD4 and VirB11 coordinate the ATP-dependent formation of a VirB10 "bridge" between inner and outer membrane subassemblies of the VirB/D4 T4SS, and that this morphogenetic event is required for T-DNA translocation across the A. tumefaciens cell envelope.

  7. Stretch-induced Ca2+ independent ATP release in hippocampal astrocytes.

    Science.gov (United States)

    Xiong, Yingfei; Teng, Sasa; Zheng, Lianghong; Sun, Suhua; Li, Jie; Guo, Ning; Li, Mingli; Wang, Li; Zhu, Feipeng; Wang, Changhe; Rao, Zhiren; Zhou, Zhuan

    2018-02-28

    Similar to neurons, astrocytes actively participate in synaptic transmission via releasing gliotransmitters. The Ca 2+ -dependent release of gliotransmitters includes glutamate and ATP. Following an 'on-cell-like' mechanical stimulus to a single astrocyte, Ca 2+ independent single, large, non-quantal, ATP release occurs. Astrocytic ATP release is inhibited by either selective antagonist treatment or genetic knockdown of P2X7 receptor channels. Our work suggests that ATP can be released from astrocytes via two independent pathways in hippocampal astrocytes; in addition to the known Ca 2+ -dependent vesicular release, larger non-quantal ATP release depends on P2X7 channels following mechanical stretch. Astrocytic ATP release is essential for brain functions such as synaptic long-term potentiation for learning and memory. However, whether and how ATP is released via exocytosis remains hotly debated. All previous studies of non-vesicular ATP release have used indirect assays. By contrast, two recent studies report vesicular ATP release using more direct assays. In the present study, using patch clamped 'ATP-sniffer cells', we re-investigated astrocytic ATP release at single-vesicle resolution in hippocampal astrocytes. Following an 'on-cell-like' mechanical stimulus of a single astrocyte, a Ca 2+ independent single large non-quantal ATP release occurred, in contrast to the Ca 2+ -dependent multiple small quantal ATP release in a chromaffin cell. The mechanical stimulation-induced ATP release from an astrocyte was inhibited by either exposure to a selective antagonist or genetic knockdown of P2X7 receptor channels. Functional P2X7 channels were expressed in astrocytes in hippocampal brain slices. Thus, in addition to small quantal ATP release, larger non-quantal ATP release depends on P2X7 channels in astrocytes. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

  8. Groundwater quality assessment for the Bear Creek hydrogeologic regime at the Y-12 Plant, 1990: Data interpretations and proposed program modifications

    International Nuclear Information System (INIS)

    1991-06-01

    This report is a detailed assessment of groundwater quality at several hazardous waste-management facilities associated with the Department of Energy (DOE) Y-12 Plant in Oak Ridge, Tennessee. The sites are located in an area defined as the Bear Creek Hydrogeologic Regime (BCHR), which is one of three hydrogeologic regimes that have been defined at the Y-12 Plant in an effort to unify and coordinate site-specific monitoring activities for planning and reporting purposes. Section 2.0 contains background information regarding the monitored sites and a discussion of the program objectives. An overview of the complex hydrogeologic system in the BCHR is provided in Section 3.0. A discussion of the interpretive assumptions used in evaluating the 1990 assessment data, a review of groundwater geochemistry and background water quality, detailed descriptions of groundwater contaminant plumes, and a discussion regarding the quality of groundwater and surface water exiting the BCHR are presented in Section 4.0. Findings of the 1990 assessment program are summarized in Section 5.0. Modification to the assessment monitoring program proposed for 1991 are in Section 6.0, and a list of references (Section 7.0) concludes the report. 20 refs., 23 figs., 12 tabs

  9. Groundwater quality assessment for the Upper East Fork Poplar Creek Hydrogeologic Regime at the Y-12 Plant: Data interpretations and proposed program modifications

    International Nuclear Information System (INIS)

    1991-06-01

    This report is a detailed assessment of groundwater quality at several hazardous waste-management facilities associated with the Department of Energy (DOE) Y-12 Plant in Oak Ridge, Tennessee. The sites are located in an area defined as the Upper East Fork Poplar Creek Hydrogeologic Regime (UEFPCHR), which is one of three hydrogeologic regimes that have been established at the Y-12 Plant in an effort to unify and coordinate site-specific monitoring activities for planning and reporting purposes. Section 2.0 contains background information and a discussion of the 1990 program objectives. An overview of the complex hydrogeologic system in the UEFPCHR is provided in Section 3.0. A discussion of the interpretive assumptions used in evaluating the 1990 assessment data, a review of groundwater geochemistry and background water quality, detailed descriptions of groundwater contaminant plumes, and a discussion regarding the quality of groundwater exiting the UEFPCHR are presented in Section 4.0. Findings of the 1990 assessment program are summarized in Section 5.0. Modifications to the assessment monitoring program proposed for 1991 are presented in Section 6.0, and a list of references (Section 7.0) concludes the report. 20 refs., 23 figs., 10 tabs

  10. A functional 12T-insertion polymorphism in the ATP1A1 promoter confers decreased susceptibility to hypertension in a male Sardinian population.

    Science.gov (United States)

    Herrera, Victoria L; Pasion, Khristine A; Moran, Ann Marie; Zaninello, Roberta; Ortu, Maria Francesca; Fresu, Giovanni; Piras, Daniela Antonella; Argiolas, Giuseppe; Troffa, Chiara; Glorioso, Valeria; Masala, Wanda; Glorioso, Nicola; Ruiz-Opazo, Nelson

    2015-01-01

    Identification of susceptibility genes for essential hypertension in humans has been a challenge due to its multifactorial pathogenesis complicated by gene-gene and gene-environment interactions, developmental programing and sex specific differences. These concurrent features make identification of causal hypertension susceptibility genes with a single approach difficult, thus requiring multiple lines of evidence involving genetic, biochemical and biological experimentation to establish causal functional mutations. Here we report experimental evidence encompassing genetic, biochemical and in vivo modeling that altogether support ATP1A1 as a hypertension susceptibility gene in males in Sardinia, Italy. ATP1A1 encodes the α1Na,K-ATPase isoform, the sole sodium pump in vascular endothelial and renal tubular epithelial cells. DNA-sequencing detected a 12-nucleotide long thymidine (12T) insertion(ins)/deletion(del) polymorphism within a poly-T sequence (38T vs 26T) in the ATP1A1 5'-regulatory region associated with hypertension in a male Sardinian population. The 12T-insertion allele confers decreased susceptibility to hypertension (P = 0.035; OR = 0.50 [0.28-0.93]) accounting for 12.1 mmHg decrease in systolic BP (P = 0.02) and 6.6 mmHg in diastolic BP (P = 0.046). The ATP1A1 promoter containing the 12T-insertion exhibited decreased transcriptional activity in in vitro reporter-assay systems, indicating decreased α1Na,K-ATPase expression with the 12T-insertion, compared with the 12T-deletion ATP1A1 promoter. To test the effects of decreased α1Na,K-ATPase expression on blood pressure, we measured blood pressure by radiotelemetry in three month-old, highly inbred heterozygous knockout ATP1A1+/- male mice with resultant 58% reduction in ATP1A1 protein levels. Male ATP1A1+/- mice showed significantly lower blood pressure (P < 0.03) than age-matched male wild-type littermate controls. Concordantly, lower ATP1A1 expression is expected to lower Na-reabsorption in the

  11. A functional 12T-insertion polymorphism in the ATP1A1 promoter confers decreased susceptibility to hypertension in a male Sardinian population.

    Directory of Open Access Journals (Sweden)

    Victoria L Herrera

    Full Text Available Identification of susceptibility genes for essential hypertension in humans has been a challenge due to its multifactorial pathogenesis complicated by gene-gene and gene-environment interactions, developmental programing and sex specific differences. These concurrent features make identification of causal hypertension susceptibility genes with a single approach difficult, thus requiring multiple lines of evidence involving genetic, biochemical and biological experimentation to establish causal functional mutations. Here we report experimental evidence encompassing genetic, biochemical and in vivo modeling that altogether support ATP1A1 as a hypertension susceptibility gene in males in Sardinia, Italy. ATP1A1 encodes the α1Na,K-ATPase isoform, the sole sodium pump in vascular endothelial and renal tubular epithelial cells. DNA-sequencing detected a 12-nucleotide long thymidine (12T insertion(ins/deletion(del polymorphism within a poly-T sequence (38T vs 26T in the ATP1A1 5'-regulatory region associated with hypertension in a male Sardinian population. The 12T-insertion allele confers decreased susceptibility to hypertension (P = 0.035; OR = 0.50 [0.28-0.93] accounting for 12.1 mmHg decrease in systolic BP (P = 0.02 and 6.6 mmHg in diastolic BP (P = 0.046. The ATP1A1 promoter containing the 12T-insertion exhibited decreased transcriptional activity in in vitro reporter-assay systems, indicating decreased α1Na,K-ATPase expression with the 12T-insertion, compared with the 12T-deletion ATP1A1 promoter. To test the effects of decreased α1Na,K-ATPase expression on blood pressure, we measured blood pressure by radiotelemetry in three month-old, highly inbred heterozygous knockout ATP1A1+/- male mice with resultant 58% reduction in ATP1A1 protein levels. Male ATP1A1+/- mice showed significantly lower blood pressure (P < 0.03 than age-matched male wild-type littermate controls. Concordantly, lower ATP1A1 expression is expected to lower Na

  12. The dynamic equilibrium between ATP synthesis and ATP consumption is lower in isolated mitochondria from myotubes established from type 2 diabetic subjects compared to lean control

    DEFF Research Database (Denmark)

    Minet, Ariane D; Gaster, Michael

    2011-01-01

    compared to lean control. The ATP synthesis rate without ATP consumption was not different between groups and there were no significant gender differences. The mitochondrial dysfunction in type 2 diabetes in vivo is partly based on a primarily impaired ATP synthesis....... or not in the mitochondria of diabetic skeletal muscle from subjects with type 2 diabetes. ATP synthesis was measured on mitochondria isolated from cultured myotubes established from lean (11/9), obese (9/11) and subjects with type 2 diabetes (9/11) (female/male, n=20 in each group), precultured under normophysiological...... selects the mitochondria based on an antibody recognizing the mitochondrial outer membrane and not by size through gradient centrifugation. The dynamic equilibrium between ATP synthesis and ATP consumption is 35% lower in isolated mitochondria from myotubes established from type 2 diabetic subjects...

  13. Wilson Disease Protein ATP7B Utilizes Lysosomal Exocytosis to Maintain Copper Homeostasis

    NARCIS (Netherlands)

    Polishchuk, Elena V.; Concilli, Mafalda; Iacobacci, Simona; Chesi, Giancarlo; Pastore, Nunzia; Piccolo, Pasquale; Paladino, Simona; Baldantoni, Daniela; van IJzendoorn, Sven C. D.; Chan, Jefferson; Chang, Christopher J.; Amoresano, Angela; Pane, Francesca; Pucci, Piero; Tarallo, Antonietta; Parenti, Giancarlo; Brunetti-Pierri, Nicola; Settembre, Carmine; Ballabio, Andrea; Polishchuk, Roman S.

    2014-01-01

    Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we

  14. Glycolysis and ATP degradation in cod ( Gadus morhua ) at subzero temperatures in relation to thaw rigor

    DEFF Research Database (Denmark)

    Cappeln, Gertrud; Jessen, Flemming

    2001-01-01

    Glycolysis was shown to occur during freezing of cod of decrease in glycogen and an increase in lactate. In addition, the ATP content decreased during freezing. Synthesis of ATP was measured as degradation of glycogen. During storage at -9 and - 12 degreesC it was found that degradation of ATP...

  15. ATP Release from Human Airway Epithelial Cells Exposed to Staphylococcus aureus Alpha-Toxin

    Directory of Open Access Journals (Sweden)

    Romina Baaske

    2016-12-01

    Full Text Available Airway epithelial cells reduce cytosolic ATP content in response to treatment with S. aureus alpha-toxin (hemolysin A, Hla. This study was undertaken to investigate whether this is due to attenuated ATP generation or to release of ATP from the cytosol and extracellular ATP degradation by ecto-enzymes. Exposure of cells to rHla did result in mitochondrial calcium uptake and a moderate decline in mitochondrial membrane potential, indicating that ATP regeneration may have been attenuated. In addition, ATP may have left the cells through transmembrane pores formed by the toxin or through endogenous release channels (e.g., pannexins activated by cellular stress imposed on the cells by toxin exposure. Exposure of cells to an alpha-toxin mutant (H35L, which attaches to the host cell membrane but does not form transmembrane pores, did not induce ATP release from the cells. The Hla-mediated ATP-release was completely blocked by IB201, a cyclodextrin-inhibitor of the alpha-toxin pore, but was not at all affected by inhibitors of pannexin channels. These results indicate that, while exposure of cells to rHla may somewhat reduce ATP production and cellular ATP content, a portion of the remaining ATP is released to the extracellular space and degraded by ecto-enzymes. The release of ATP from the cells may occur directly through the transmembrane pores formed by alpha-toxin.

  16. Stimulation of acetoin production in metabolically engineered Lactococcus lactis by increasing ATP demand

    DEFF Research Database (Denmark)

    Liu, Jianming; Kandasamy, Vijayalakshmi; Würtz, Anders

    2016-01-01

    Having a sufficient supply of energy, usually in the form of ATP, is essential for all living organisms. In this study, however, we demonstrate that it can be beneficial to reduce ATP availability when the objective is microbial production. By introducing the ATP hydrolyzing F1-ATPase into a Lact...

  17. A comparative study of ATPase subunit 9 (Atp9) gene between ...

    African Journals Online (AJOL)

    ATPase subunit 9 gene (Atp9) is an important functional gene in mitochondria, and is closely related with energy supply. RNA editing of atp9 gene was associated with male sterility in plants. In this study, the atp9 gene in soybeans was cloned from a soybean cytoplasmic male sterile line NJCMS2A and its maintainer line ...

  18. Statistical Mechanics Analysis of ATP Binding to a Multisubunit Enzyme

    International Nuclear Information System (INIS)

    Zhang Yun-Xin

    2014-01-01

    Due to inter-subunit communication, multisubunit enzymes usually hydrolyze ATP in a concerted fashion. However, so far the principle of this process remains poorly understood. In this study, from the viewpoint of statistical mechanics, a simple model is presented. In this model, we assume that the binding of ATP will change the potential of the corresponding enzyme subunit, and the degree of this change depends on the state of its adjacent subunits. The probability of enzyme in a given state satisfies the Boltzmann's distribution. Although it looks much simple, this model can fit the recent experimental data of chaperonin TRiC/CCT well. From this model, the dominant state of TRiC/CCT can be obtained. This study provide a new way to understand biophysical processe by statistical mechanics analysis. (interdisciplinary physics and related areas of science and technology)

  19. Structure and mechanism of ATP-dependent phospholipid transporters

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura; Poulsen, Lisbeth Rosager; Bailly, Aurélien

    2015-01-01

    Background ATP-binding cassette (ABC) transporters and P4-ATPases are two large and seemingly unrelated families of primary active pumps involved in moving phospholipids from one leaflet of a biological membrane to the other. Scope of review This review aims to identify common mechanistic features...... in the way phospholipid flipping is carried out by two evolutionarily unrelated families of transporters. Major conclusions Both protein families hydrolyze ATP, although they employ different mechanisms to use it, and have a comparable size with twelve transmembrane segments in the functional unit. Further......, despite differences in overall architecture, both appear to operate by an alternating access mechanism and during transport they might allow access of phospholipids to the internal part of the transmembrane domain. The latter feature is obvious for ABC transporters, but phospholipids and other hydrophobic...

  20. PAR-2 activation enhances weak acid-induced ATP release through TRPV1 and ASIC sensitization in human esophageal epithelial cells.

    Science.gov (United States)

    Wu, Liping; Oshima, Tadayuki; Shan, Jing; Sei, Hiroo; Tomita, Toshihiko; Ohda, Yoshio; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

    2015-10-15

    Esophageal visceral hypersensitivity has been proposed to be the pathogenesis of heartburn sensation in nonerosive reflux disease. Protease-activated receptor-2 (PAR-2) is expressed in human esophageal epithelial cells and is believed to play a role in inflammation and sensation. PAR-2 activation may modulate these responses through adenosine triphosphate (ATP) release, which is involved in transduction of sensation and pain. The transient receptor potential vanilloid receptor 1 (TRPV1) and acid-sensing ion channels (ASICs) are both acid-sensitive nociceptors. However, the interaction among these molecules and the mechanisms of heartburn sensation are still not clear. We therefore examined whether ATP release in human esophageal epithelial cells in response to acid is modulated by TRPV1 and ASICs and whether PAR-2 activation influences the sensitivity of TRPV1 and ASICs. Weak acid (pH 5) stimulated the release of ATP from primary human esophageal epithelial cells (HEECs). This effect was significantly reduced after pretreatment with 5-iodoresiniferatoxin (IRTX), a TRPV1-specific antagonist, or with amiloride, a nonselective ASIC blocker. TRPV1 and ASIC3 small interfering RNA (siRNA) transfection also decreased weak acid-induced ATP release. Pretreatment of HEECs with trypsin, tryptase, or a PAR-2 agonist enhanced weak acid-induced ATP release. Trypsin treatment led to the phosphorylation of TRPV1. Acid-induced ATP release enhancement by trypsin was partially blocked by IRTX, amiloride, or a PAR-2 antagonist. Conversely, acid-induced ATP release was augmented by PAR-2 activation through TRPV1 and ASICs. These findings suggested that the pathophysiology of heartburn sensation or esophageal hypersensitivity may be associated with the activation of PAR-2, TRPV1, and ASICs. Copyright © 2015 the American Physiological Society.

  1. Alternative mitochondrial functions in cell physiopathology: beyond ATP production

    Directory of Open Access Journals (Sweden)

    Kowaltowski A.J.

    2000-01-01

    Full Text Available It is well known that mitochondria are the main site for ATP generation within most tissues. However, mitochondria also participate in a surprising number of alternative activities, including intracellular Ca2+ regulation, thermogenesis and the control of apoptosis. In addition, mitochondria are the main cellular generators of reactive oxygen species, and may trigger necrotic cell death under conditions of oxidative stress. This review concentrates on these alternative mitochondrial functions, and their role in cell physiopathology.

  2. Catalytic strategy used by the myosin motor to hydrolyze ATP.

    Science.gov (United States)

    Kiani, Farooq Ahmad; Fischer, Stefan

    2014-07-22

    Myosin is a molecular motor responsible for biological motions such as muscle contraction and intracellular cargo transport, for which it hydrolyzes adenosine 5'-triphosphate (ATP). Early steps of the mechanism by which myosin catalyzes ATP hydrolysis have been investigated, but still missing are the structure of the final ADP·inorganic phosphate (Pi) product and the complete pathway leading to it. Here, a comprehensive description of the catalytic strategy of myosin is formulated, based on combined quantum-classical molecular mechanics calculations. A full exploration of catalytic pathways was performed and a final product structure was found that is consistent with all experiments. Molecular movies of the relevant pathways show the different reorganizations of the H-bond network that lead to the final product, whose γ-phosphate is not in the previously reported HPγO4(2-) state, but in the H2PγO4(-) state. The simulations reveal that the catalytic strategy of myosin employs a three-pronged tactic: (i) Stabilization of the γ-phosphate of ATP in a dissociated metaphosphate (PγO3(-)) state. (ii) Polarization of the attacking water molecule, to abstract a proton from that water. (iii) Formation of multiple proton wires in the active site, for efficient transfer of the abstracted proton to various product precursors. The specific role played in this strategy by each of the three loops enclosing ATP is identified unambiguously. It explains how the precise timing of the ATPase activation during the force generating cycle is achieved in myosin. The catalytic strategy described here for myosin is likely to be very similar in most nucleotide hydrolyzing enzymes.

  3. Efficient purification and reconstitution of ATP binding cassette transporter B6 (ABCB6) for functional and structural studies.

    Science.gov (United States)

    Chavan, Hemantkumar; Khan, Mohiuddin Md Taimur; Tegos, George; Krishnamurthy, Partha

    2013-08-02

    The mitochondrial ATP binding cassette transporter ABCB6 has been associated with a broad range of physiological functions, including growth and development, therapy-related drug resistance, and the new blood group system Langereis. ABCB6 has been proposed to regulate heme synthesis by shuttling coproporphyrinogen III from the cytoplasm into the mitochondria. However, direct functional information of the transport complex is not known. To understand the role of ABCB6 in mitochondrial transport, we developed an in vitro system with pure and active protein. ABCB6 overexpressed in HEK293 cells was solubilized from mitochondrial membranes and purified to homogeneity. Purified ABCB6 showed a high binding affinity for MgATP (Kd = 0.18 μM) and an ATPase activity with a Km of 0.99 mM. Reconstitution of ABCB6 into liposomes allowed biochemical characterization of the ATPase including (i) substrate-stimulated ATPase activity, (ii) transport kinetics of its proposed endogenous substrate coproporphyrinogen III, and (iii) transport kinetics of substrates identified using a high throughput screening assay. Mutagenesis of the conserved lysine to alanine (K629A) in the Walker A motif abolished ATP hydrolysis and substrate transport. These results suggest a direct interaction between mitochondrial ABCB6 and its transport substrates that is critical for the activity of the transporter. Furthermore, the simple immunoaffinity purification of ABCB6 to near homogeneity and efficient reconstitution of ABCB6 into liposomes might provide the basis for future studies on the structure/function of ABCB6.

  4. Decipher the mechanisms of protein conformational changes induced by nucleotide binding through free-energy landscape analysis: ATP binding to Hsp70.

    Directory of Open Access Journals (Sweden)

    Adrien Nicolaï

    Full Text Available ATP regulates the function of many proteins in the cell by transducing its binding and hydrolysis energies into protein conformational changes by mechanisms which are challenging to identify at the atomic scale. Based on molecular dynamics (MD simulations, a method is proposed to analyze the structural changes induced by ATP binding to a protein by computing the effective free-energy landscape (FEL of a subset of its coordinates along its amino-acid sequence. The method is applied to characterize the mechanism by which the binding of ATP to the nucleotide-binding domain (NBD of Hsp70 propagates a signal to its substrate-binding domain (SBD. Unbiased MD simulations were performed for Hsp70-DnaK chaperone in nucleotide-free, ADP-bound and ATP-bound states. The simulations revealed that the SBD does not interact with the NBD for DnaK in its nucleotide-free and ADP-bound states whereas the docking of the SBD was found in the ATP-bound state. The docked state induced by ATP binding found in MD is an intermediate state between the initial nucleotide-free and final ATP-bound states of Hsp70. The analysis of the FEL projected along the amino-acid sequence permitted to identify a subset of 27 protein internal coordinates corresponding to a network of 91 key residues involved in the conformational change induced by ATP binding. Among the 91 residues, 26 are identified for the first time, whereas the others were shown relevant for the allosteric communication of Hsp70 s in several experiments and bioinformatics analysis. The FEL analysis revealed also the origin of the ATP-induced structural modifications of the SBD recently measured by Electron Paramagnetic Resonance. The pathway between the nucleotide-free and the intermediate state of DnaK was extracted by applying principal component analysis to the subset of internal coordinates describing the transition. The methodology proposed is general and could be applied to analyze allosteric communication in

  5. Translocation, switching and gating: potential roles for ATP in long-range communication on DNA by Type III restriction endonucleases.

    Science.gov (United States)

    Szczelkun, Mark D

    2011-04-01

    To cleave DNA, the Type III RM (restriction-modification) enzymes must communicate the relative orientation of two recognition sequences, which may be separated by many thousands of base pairs. This long-range interaction requires ATP hydrolysis by a helicase domain, and both active (DNA translocation) and passive (DNA sliding) modes of motion along DNA have been proposed. Potential roles for ATP binding and hydrolysis by the helicase domains are discussed, with a focus on bipartite ATPases that act as molecular switches.

  6. Quantum-mechanical analysis of amino acid residues function in the proton transport during F0F1-ATP synthase catalytic cycle

    Science.gov (United States)

    Ivontsin, L. A.; Mashkovtseva, E. V.; Nartsissov, Ya R.

    2017-11-01

    Implications of quantum-mechanical approach to the description of proton transport in biological systems are a tempting subject for an overlapping of fundamental physics and biology. The model of proton transport through the integrated membrane enzyme FoF1-ATP synthase responsible for ATP synthesis was developed. The estimation of the mathematical expectation of the proton transfer time through the half-channel was performed. Observed set of proton pathways through the inlet half-channel showed the nanosecond timescale highly dependable of some amino acid residues. There were proposed two types of crucial amino acids: critically localized (His245) and being a part of energy conserving system (Asp119).

  7. Persister formation in Staphylococcus aureus is associated with ATP depletion

    Energy Technology Data Exchange (ETDEWEB)

    Conlon, Brian P.; Rowe, Sarah E.; Gandt, Autumn Brown; Nuxoll, Austin S.; Donegan, Niles P.; Zalis, Eliza A.; Clair, Geremy; Adkins, Joshua N.; Cheung, Ambrose L.; Lewis, Kim

    2016-04-18

    Persisters are dormant phenotypic variants of bacterial cells that are tolerant to killing by antibiotics1. Persisters are associated with chronic bacterial infection and antibiotic treatment failure. In Escherichia coli, toxin/antitoxin (TA) modules are responsible for persister formation. The mechanism of persister formation in Gram positive bacteria is unknown. Staphylococcus aureus is a major human pathogen, responsible for a variety of chronic and relapsing infections such as osteomyelitis, endocarditis and infections of implanted devices. Deleting TA modules in S. aureus did not affect the level of persisters. Here we show that S. aureus persisters are produced due to a stochastic entrance to stationary phase accompanied by a drop in intracellular ATP. Cells expressing stationary state markers are present throughout the growth phase, increasing in frequency with cell density. Cell sorting revealed that expression of stationary markers was associated with a 100-1000 fold increased likelihood of survival to antibiotic challenge. We find that the antibiotic tolerance of these cells is due to a drop in intracellular ATP. The ATP level of the cell is predictive of bactericidal antibiotic efficacy and explains bacterial tolerance to antibiotic treatment.

  8. Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition

    Science.gov (United States)

    Park, Dohyun; Jeong, Heeyoon; Lee, Mi Nam; Koh, Ara; Kwon, Ohman; Yang, Yong Ryoul; Noh, Jungeun; Suh, Pann-Ghill; Park, Hwangseo; Ryu, Sung Ho

    2016-01-01

    Resveratrol (RSV) is a natural polyphenol that has a beneficial effect on health, and resveratrol-induced autophagy has been suggested to be a key process in mediating many beneficial effects of resveratrol, such as reduction of inflammation and induction of cancer cell death. Although various resveratrol targets have been suggested, the molecule that mediates resveratrol-induced autophagy remains unknown. Here, we demonstrate that resveratrol induces autophagy by directly inhibiting the mTOR-ULK1 pathway. We found that inhibition of mTOR activity and presence of ULK1 are required for autophagy induction by resveratrol. In line with this mTOR dependency, we found that resveratrol suppresses the viability of MCF7 cells but not of SW620 cells, which are mTOR inhibitor sensitive and insensitive cancer cells, respectively. We also found that resveratrol-induced cancer cell suppression occurred ULK1 dependently. For the mechanism of action of resveratrol on mTOR inhibition, we demonstrate that resveratrol directly inhibits mTOR. We found that resveratrol inhibits mTOR by docking onto the ATP-binding pocket of mTOR (i.e., it competes with ATP). We propose mTOR as a novel direct target of resveratrol, and inhibition of mTOR is necessary for autophagy induction. PMID:26902888

  9. Membrane porters of ATP-binding cassette transport systems are polyphyletic.

    Science.gov (United States)

    Wang, Bin; Dukarevich, Maxim; Sun, Eric I; Yen, Ming Ren; Saier, Milton H

    2009-09-01

    The ATP-binding cassette (ABC) superfamily consists of both importers and exporters. These transporters have, by tradition, been classified according to the ATP hydrolyzing constituents, which are monophyletic. The evolutionary origins of the transmembrane porter proteins/domains are not known. Using five distinct computer programs, we here provide convincing statistical data suggesting that the transmembrane domains of ABC exporters are polyphyletic, having arisen at least three times independently. ABC1 porters arose by intragenic triplication of a primordial two-transmembrane segment (TMS)-encoding genetic element, yielding six TMS proteins. ABC2 porters arose by intragenic duplication of a dissimilar primordial three-TMS-encoding genetic element, yielding a distinctive protein family, nonhomologous to the ABC1 proteins. ABC3 porters arose by duplication of a primordial four-TMS-encoding genetic element, yielding either eight- or 10-TMS proteins. We assign each of 48 of the 50 currently recognized families of ABC exporters to one of the three evolutionarily distinct ABC types. Currently available high-resolution structural data for ABC porters are fully consistent with our findings. These results provide guides for future structural and mechanistic studies of these important transport systems.

  10. Prevalence of Metabolic Syndrome among Malaysians using the International Diabetes Federation, National Cholesterol Education Program and Modified World Health Organization Definitions.

    Science.gov (United States)

    Bee, Ying Tan; Haresh, Kumar Kantilal; Rajibans, Singh

    2008-03-01

    The World Health Organization (WHO), National Cholesterol Education Program Adults Treatment Panel III (NCEP ATP III) and International Diabetes Federation (IDF) have proposed different criteria to diagnose metabolic syndrome (MetS). However, there is no single definition to accurately diagnose MetS. The objective of this study is to estimate the prevalence of MetS using WHO, NCEP ATP III and IDF in the Malaysian community, and to determine the concordance between these definitions for MetS. 109 men and women aged > 30 years participated in the study, and the prevalence of MetS was determined according to the three definitions. Weight, height, body mass index (BMI), waist-hip circumference, blood pressure, blood lipid profile and plasma fasting glucose were measured. In order to determine the concordance between IDF and the other two definitions, the kappa index (κ-test) was used. The prevalence of MetS (95% confidence interval) was 22.9% (22.8-23.1) by IDF definition, 16.5% (16.3-16.9) by NCEP ATP III definition and 6.4% (6.2-6.6) by modified WHO definition. The sensitivity and specificity of IDF against NCEP ATP III were 88.9% and 90.1% respectively, IDF against WHO definition were 85.7% and 81.4%. The κ statistics for the agreement of the IDF definition was 68.3 ± 0.1 with the NCEP ATP III, and 30.5 ± 0.1 with the modified WHO definition. The prevalence of the MetS among respondents using the IDF definition was highest, followed by NCEP ATP III, and finally modified WHO definition. There was a good concordance between the IDF and NCEP ATP III definitions, and a low concordance between IDF and modified WHO definitions.

  11. A goal programming approach for a joint design of macroeconomic and environmental policies: a methodological proposal and an application to the Spanish economy.

    Science.gov (United States)

    André, Francisco J; Cardenete, M Alejandro; Romero, Carlos

    2009-05-01

    The economic policy needs to pay increasingly more attention to the environmental issues, which requires the development of methodologies able to incorporate environmental, as well as macroeconomic, goals in the design of public policies. Starting from this observation, this article proposes a methodology based upon a Simonian satisficing logic made operational with the help of goal programming (GP) models, to address the joint design of macroeconomic and environmental policies. The methodology is applied to the Spanish economy, where a joint policy is elicited, taking into consideration macroeconomic goals (economic growth, inflation, unemployment, public deficit) and environmental goals (CO(2), NO( x ) and SO( x ) emissions) within the context of a computable general equilibrium model. The results show how the government can "fine-tune" its policy according to different criteria using GP models. The resulting policies aggregate the environmental and the economic goals in different ways: maximum aggregate performance, maximum balance and a lexicographic hierarchy of the goals.

  12. Osteoblast-like MC3T3-E1 Cells Prefer Glycolysis for ATP Production but Adipocyte-like 3T3-L1 Cells Prefer Oxidative Phosphorylation.

    Science.gov (United States)

    Guntur, Anyonya R; Gerencser, Akos A; Le, Phuong T; DeMambro, Victoria E; Bornstein, Sheila A; Mookerjee, Shona A; Maridas, David E; Clemmons, David E; Brand, Martin D; Rosen, Clifford J

    2018-06-01

    Mesenchymal stromal cells (MSCs) are early progenitors that can differentiate into osteoblasts, chondrocytes, and adipocytes. We hypothesized that osteoblasts and adipocytes utilize distinct bioenergetic pathways during MSC differentiation. To test this hypothesis, we compared the bioenergetic profiles of preosteoblast MC3T3-E1 cells and calvarial osteoblasts with preadipocyte 3T3L1 cells, before and after differentiation. Differentiated MC3T3-E1 osteoblasts met adenosine triphosphate (ATP) demand mainly by glycolysis with minimal reserve glycolytic capacity, whereas nondifferentiated cells generated ATP through oxidative phosphorylation. A marked Crabtree effect (acute suppression of respiration by addition of glucose, observed in both MC3T3-E1 and calvarial osteoblasts) and smaller mitochondrial membrane potential in the differentiated osteoblasts, particularly those incubated at high glucose concentrations, indicated a suppression of oxidative phosphorylation compared with nondifferentiated osteoblasts. In contrast, both nondifferentiated and differentiated 3T3-L1 adipocytes met ATP demand primarily by oxidative phosphorylation despite a large unused reserve glycolytic capacity. In sum, we show that nondifferentiated precursor cells prefer to use oxidative phosphorylation to generate ATP; when they differentiate to osteoblasts, they gain a strong preference for glycolytic ATP generation, but when they differentiate to adipocytes, they retain the strong preference for oxidative phosphorylation. Unique metabolic programming in mesenchymal progenitor cells may influence cell fate and ultimately determine the degree of bone formation and/or the development of marrow adiposity. © 2018 American Society for Bone and Mineral Research. © 2018 American Society for Bone and Mineral Research.

  13. Extracellular ATP4- promotes cation fluxes in the J774 mouse macrophage cell line

    International Nuclear Information System (INIS)

    Steinberg, T.H.; Silverstein, S.C.

    1987-01-01

    Extracellular ATP stimulates transmembrane ion fluxes in the mouse macrophage cell line J774. In the presence of Mg2+, nonhydrolyzable ATP analogs and other purine and pyrimidine nucleotides do not elicit this response, suggesting the presence of a specific receptor for ATP on the macrophage plasma membrane. One candidate for such a receptor is the ecto-ATPase expressed on these cells. We, therefore, investigated the role of this enzyme in ATP-induced 86 Rb+ efflux in J774 cells. The ecto-ATPase had a broad nucleotide specificity and did not hydrolyze extracellular ATP in the absence of divalent cations. 86 Rb+ efflux was not blocked by inhibition of the ecto-ATPase and did not require Ca2+ or Mg2+. In fact, ATP-stimulated 86 Rb+ efflux was inhibited by Mg2+ and correlated with the availability of ATP4- in the medium. In the absence of divalent cations, the slowly hydrolyzable ATP analogs adenosine 5'-(beta, gamma-imido)triphosphate (AMP-PNP) and adenosine 5'-O-(3-thio)triphosphate (ATP-gamma-S) also stimulated 86 Rb+ efflux, albeit at higher concentrations than that required for ATP4-. Exposure of J774 cells to 10 mM ATP for 45 min caused death of 95% of cells. By this means we selected variant J774 cells that did not exhibit 86 Rb+ efflux in the presence of extracellular ATP but retained ecto-ATPase activity. These results show that the ecto-ATPase of J774 cells does not mediate the effects of ATP on these cells; that ATP4- and not MgATP2- promotes 86 Rb+ efflux from these cells; and that hydrolysis of ATP is not required to effect this change in membrane permeability. These findings suggest that J774 cells possess a plasma membrane receptor which binds ATP4-, AMP-PNP, and ATP-gamma-S, and that the ecto-ATPase limits the effects of ATP on these cells by hydrolyzing Mg-ATP2-

  14. Small amounts of functional ATP7A protein permit mild phenotype

    DEFF Research Database (Denmark)

    Møller, Lisbeth Birk

    2015-01-01

    concentrations, ATP7A shifts to the post-Golgi compartments or to the plasma membrane to export copper out of the cell. Impaired copper-regulation trafficking has been observed for ATP7A mutants, but its impact on the clinical outcome is not clear. The major problem in patients with MD seems to be insufficient...... of missense mutations on structural models of the ATP7A protein suggests that affected conserved residues generally lead to a severe phenotype. The ATP7A protein traffics within the cells. At low copper levels, ATP7A locates to the Trans-Golgi Network (TGN) to load cuproenzymes with copper, whereas at higher...

  15. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

    DEFF Research Database (Denmark)

    Heinzen, Erin L; Swoboda, Kathryn J; Hitomi, Yuki

    2012-01-01

    and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation...... affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3....

  16. Implementation proposal of a water conservation and reuse program at the TRANSPETRO; Proposta de implementacao de um programa de conservacao e reuso de agua na TRANSPETRO

    Energy Technology Data Exchange (ETDEWEB)

    Martini, Andrea Dietrich; Alves, Anibal Jose Constantino; Melo Neto, Joao Evangelista de [TRANSPETRO - PETROBRAS Transporte S.A., Rio de Janeiro, RJ (Brazil)

    2008-07-01

    The great amount of water that is used by industries and the ascendant preoccupation about the quantity and quality of water resources in Brazil and in the world are important justifications to start thinking of more efficient proposals for water application. Between the alternatives for water consume reduction in industry there is the reuse as the principle of those. A study of PricewaterhouseCoopers about this matter at the main national industries identified that 48% have reuse goals. The present work intends to show a methodology and the justifications to implement a conservation and water reuse program at the Terminals of PETROBRAS Transporte S.A. - TRANSPETRO. Therefore are presented the many possible applications for reuse water at TRANSPETRO and the stages to the implementation of this kind of project. The methodology presented, based on FIESP Proposal, has as the objective both water consumed reduction and water discharged reduction. Then it must be realized an identification of several water consumed sources and water discharged sources, focusing on the many reuse possible. (author)

  17. Clinically oriented device programming in bradycardia patients: part 2 (atrioventricular blocks and neurally mediated syncope). Proposals from AIAC (Italian Association of Arrhythmology and Cardiac Pacing).

    Science.gov (United States)

    Palmisano, Pietro; Ziacchi, Matteo; Biffi, Mauro; Ricci, Renato P; Landolina, Maurizio; Zoni-Berisso, Massimo; Occhetta, Eraldo; Maglia, Giampiero; Botto, Gianluca; Padeletti, Luigi; Boriani, Giuseppe

    2018-04-01

    : The purpose of this two-part consensus document is to provide specific suggestions (based on an extensive literature review) on appropriate pacemaker setting in relation to patients' clinical features. In part 2, criteria for pacemaker choice and programming in atrioventricular blocks and neurally mediate syncope are proposed. The atrioventricular blocks can be paroxysmal or persistent, isolated or associated with sinus node disease. Neurally mediated syncope can be related to carotid sinus syndrome or cardioinhibitory vasovagal syncope. In sinus rhythm, with persistent atrioventricular block, we considered appropriate the activation of mode-switch algorithms, and algorithms for auto-adaptive management of the ventricular pacing output. If the atrioventricular block is paroxysmal, in addition to algorithms mentioned above, algorithms to maximize intrinsic atrioventricular conduction should be activated. When sinus node disease is associated with atrioventricular block, the activation of rate-responsive function in patients with chronotropic incompetence is appropriate. In permanent atrial fibrillation with atrioventricular block, algorithms for auto-adaptive management of the ventricular pacing output should be activated. If the atrioventricular block is persistent, the activation of rate-responsive function is appropriate. In carotid sinus syndrome, adequate rate hysteresis should be programmed. In vasovagal syncope, specialized sensing and pacing algorithms designed for reflex syncope prevention should be activated.

  18. Proposal for a program in particle-beam radiation therapy in the United States. A report from the Committee for Radiation Oncology Studies (CROS) and its particle subcommittee

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    The Program for Particle Therapy proposes utilization of hospital-based particle generators in a nationwide program to evaluate, through meaningful clinical trials, article radiation therapy and the impact its utilization can have in cancer care. The scientific rationale for use of particle therapy compared to conventional radiation in the effort to achieve uncomplicated local control of cancer, to heal, cure and palliate the patient, indicates the advantages of particle therapy consist of either or both (a) enhanced biological effect and (b) physical properties leading to improvement in dose distribution. Any new modality enabling the therapist to increase dose to tumor, while sparing critical normal tissue, can enhance local control and benefit systemic therapy. Limited clinical trials to date warrant further definitive clinical study of particle beams. Physical and biologic considerations of fast-neutron beams have been essentially completed; equipment design, availability, and predicted reliability are good; and the medical community has indicated support of further study. A major clinical investigation can be implemented to provide the scientific basis for judging clinical merit of use of high LET radiations. Concurrently, the first phase of work can be started with protons, negative pions, and heavy ions. It is anticipated that clinical results will accrue much more rapidly with hospital-based facilities in two phases, over a 10-year period

  19. Effect of hydrogen peroxide on the main kinetic parameters of ATP hydrolysis by ouabain sensitive Na+, K+-ATP-ase in spermatozoa of infertile men

    Directory of Open Access Journals (Sweden)

    Р. В. Фафула

    2017-12-01

    Full Text Available Background: It is known that Na+,K+-ATP-ase plays important role in physiology of spermatozoa including their motility. Na+,K+-ATP-ase is one of the targets for reactive oxygen species. Hyperproduction of reactive oxygen species can damage sperm cells and it is considered to be as one of the mechanisms of male infertility. Objectives: To evaluate the H2O2 effect on the main kinetic parameters of ATP hydrolysis by ouabain-sensitive Na+,K+-ATPase of spermatozoa of fertile (normozoospermia and infertility men (asthenozoospermia. Materials and methods: Na+, K+-ATP-ase activity was determined spectrophotometrically by production of Pi. Concentration dependencies ware linearized in Lineweaver-Burk plot. Results: Effective inhibitory effect of H2O2 on ouabain-sensitive Na+,K+-ATP-ase activity of sperm cells of fertile and infertile men was demonstrated. The effects of H2O2 on the main kinetic parameters of the ATP hydrolysis with the involvement of Na+, K+-ATP-ase was studied. In the whole range of studied concentrations of ATP the Na+, K+-ATP-ase activity of spermatozoa of fertile and infertile men was reduced in the presence of H2O2 in the incubation medium. However, the optimal activity of the Na+, K+-ATP-ase activity of sperm cells in both normozoospermic and asthenozoospermic men was observed in the presence of 5 mM ATP in the incubation medium. By linearization of concentration curves in Lineweaver-Burk plot the main kinetic parameters of Na+, K+-activated, Mg2+-dependent ATP hydrolysis in the sperm cells of fertile and infertile men were determined. Under the effect of H2O2, the affinity constant of enzyme to ATP in normozoospermic and asthenozoospermic men increases several times. The initial maximum rate of ATP hydrolysis was significantly reduced only in the spermatozoa of fertile men with normozoospermia. Conclusions: Under conditions of H2O2-induced oxidative stress the inhibition of ouabain-sensitive Na+,K+-ATP-ase activity in sperm cells

  20. Towards a multiscale description of microvascular flow regulation: O2-dependent release of ATP from human erythrocytes and the distribution of ATP in capillary networks

    Directory of Open Access Journals (Sweden)

    Daniel eGoldman

    2012-07-01

    Full Text Available Integration of the numerous mechanisms that have been suggested to contribute to optimization of O2 supply to meet O2 need in skeletal muscle requires a systems biology approach which permits quantification of these physiological processes over a wide range of length scales. Here we describe two individual computational models based on in vivo and in vitro studies which, when incorporated into a single robust multiscale model, will provide information on the role of erythrocyte-released ATP in perfusion distribution in skeletal muscle under both physiological and pathophysiological conditions. Healthy human erythrocytes exposed to low O2 tension release ATP via a well characterized signaling pathway requiring activation of the G-protein, Gi, and adenylyl cyclase leading to increases in cAMP. This cAMP then activates PKA and subsequently CFTR culminating in ATP release via pannexin 1. A critical control point in this pathway is the level of cAMP which is regulated by pathway-specific phosphodiesterases. Using time constants (~100ms that are consistent with measured erythrocyte ATP release, we have constructed a dynamic model of this pathway. The model predicts levels of ATP release consistent with measurements obtained over a wide range of hemoglobin O2 saturations (sO2. The model further predicts how insulin, at concentrations found in prediabetes, enhances the activity of PDE3 and reduces intracellular cAMP levels leading to decreased low O2-induced ATP release from erythrocytes. The second model, which couples O2 and ATP transport in capillary networks, shows how intravascular ATP and the resulting conducted vasodilation are affected by local sO2, convection and ATP degradation. This model also predicts network-level effects of decreased ATP release resulting from elevated insulin levels. Taken together, these models lay the groundwork for investigating the systems biology of the regulation of microvascular perfusion distribution by

  1. Extracellular ATP inhibits Schwann cell dedifferentiation and proliferation in an ex vivo model of Wallerian degeneration

    International Nuclear Information System (INIS)

    Shin, Youn Ho; Lee, Seo Jin; Jung, Junyang

    2013-01-01

    Highlights: ► ATP-treated sciatic explants shows the decreased expression of p75NGFR. ► Extracellular ATP inhibits the expression of phospho-ERK1/2. ► Lysosomal exocytosis is involved in Schwann cell dedifferentiation. ► Extracellular ATP blocks Schwann cell proliferation in sciatic explants. -- Abstract: After nerve injury, Schwann cells proliferate and revert to a phenotype that supports nerve regeneration. This phenotype-changing process can be viewed as Schwann cell dedifferentiation. Here, we investigated the role of extracellular ATP in Schwann cell dedifferentiation and proliferation during Wallerian degeneration. Using several markers of Schwann cell dedifferentiation and proliferation in sciatic explants, we found that extracellular ATP inhibits Schwann cell dedifferentiation and proliferation during Wallerian degeneration. Furthermore, the blockage of lysosomal exocytosis in ATP-treated sciatic explants is sufficient to induce Schwann cell dedifferentiation. Together, these findings suggest that ATP-induced lysosomal exocytosis may be involved in Schwann cell dedifferentiation.

  2. Effect of irradiation on detection of bacteria in dehydrated vegetables with ATP bioluminescence assay

    International Nuclear Information System (INIS)

    Xiao Huan; Luo Shishi; Wang Zegang; Feng Min; Zhu Jiating; Chen Xiulan; Zhai Jianqing

    2011-01-01

    ATP bioluminescence intensity of 4 kinds of irradiated dehydrated vegetables was inconsistent with the bacteria number, the reasons were investigated in this paper. Results showed that irradiation had little effect on background luminescence, and there was no effect on luciferase-luminous system. When irradiation killed the bacteria, the ATPase activity also decreased. As a result, the ATP content in bacteria didn't decreased with the killed of bacteria, which contributed to the increase of free ATP in ATP extract and finally led to the disagreement between the bioluminescence intensity and the actual number of bacteria. When the free ATP in the dehydrated vegetable was removed, the bioluminescence intensity of ATP extract was consistent with the actual number of bacteria in irradiated dehydrated vegetable and ATP bioluminescence technology could be used in bacteria detection of irradiated samples. (authors)

  3. ATP-independent DNA synthesis in Vaccinia-infected L cells

    International Nuclear Information System (INIS)

    Berger, N.A.; Kauff, R.A.; Sikorski, G.W.

    1978-01-01

    Mouse L cells can be made permeable to exogenous nucleotides by a cold shock in 0.01 M Tris . HCl pH 7.8, 0.25 M sucrose, 1 mM EDTA, 30 mM 2-mercaptoethanol and 4 mM MgCl 2 . DNA synthesis in permeabilized L cells requires ATP whereas DNA synthesis in permeabilized L cells that are infected with Vaccinia virus is ATP-independent. Permeabilized L cells that are infected with ultraviolet-irradiated virus show a marked suppression of DNA synthesis which is not corrected by an excess of deoxynucleoside triphosphates and ATP. The ATP-dependent and ATP-independent processes of DNA synthesis are inhibited to the same extent by Mal-Net, pHMB, ara CTP and phosphonoacetate. Concentrations of daunorubicin and cytembena, which cause marked inhibition of the ATP-dependent enzymes, only cause partial inhibition of the ATP-independent enzymes. (Auth.)

  4. ATP Modifies the Proteome of Extracellular Vesicles Released by Microglia and Influences Their Action on Astrocytes

    Directory of Open Access Journals (Sweden)

    Francesco Drago

    2017-12-01

    Full Text Available Extracellular ATP is among molecules promoting microglia activation and inducing the release of extracellular vesicles (EVs, which are potent mediators of intercellular communication between microglia and the microenvironment. We previously showed that EVs produced under ATP stimulation (ATP-EVs propagate a robust inflammatory reaction among astrocytes and microglia in vitro and in mice with subclinical neuroinflammation (Verderio et al., 2012. However, the proteome of EVs released upon ATP stimulation has not yet been elucidated. In this study we applied a label free proteomic approach to characterize the proteome of EVs released constitutively and during microglia activation with ATP. We show that ATP drives sorting in EVs of a set of proteins implicated in cell adhesion/extracellular matrix organization, autophagy-lysosomal pathway and cellular metabolism, that may influence the response of recipient astrocytes to EVs. These data provide new clues to molecular mechanisms involved in microglia response to ATP and in microglia signaling to the environment via EVs.

  5. Formative evaluation of a proposed mHealth program for childhood illness management in a resource-limited setting in Peru

    Directory of Open Access Journals (Sweden)

    T. A. Calderón

    2015-08-01

    Full Text Available OBJECTIVE: To conduct a formative evaluation of a proposed mobile health (mHealth program designed to educate caregivers about management of common childhood illnesses. METHODS: A cluster-randomized sample (n = 220 of mothers in Cono Norte, Arequipa, Peru with at least one child under five completed an iPad-based survey. This descriptive study examined trends in mobile phone ownership and feasibility of and interest in mHealth across sociodemographic categories. Fisher's exact tests were used to evaluate associations. Univariate logistic regression models were fitted to calculate odds ratios and 95% confidence intervals. RESULTS: Of 220 participants, 82.3% and 95.0% reported mobile phone ownership and access, respectively. Ownership was significantly associated with educational level (P = 0.031; however, even among mothers with the lowest education, ownership approached 80%. Educational level and age, respectively, were associated with the ability to open (P < 0.001; P < 0.001, read (P < 0.001; P < 0.001, write (P < 0.001; P < 0.001, and send (P = 0.006; P = 0.047 text messages. Over 85% of mothers were interested in using their mobile phones to receive health advice for their child and to seek help during illness. Regression analyses revealed that ability to use a mobile phone was positively associated with the mother's intention to participate in the mHealth program. CONCLUSIONS: The study findings confirm widespread access to mobile phones and sufficient ability to utilize text messaging within this population of caregivers. In addition to access and feasibility, high levels of interest in using mobile phones for health-related purposes suggest the potential value associated with an mHealth program designed to improve childhood illness management in this community.

  6. [Stabilization of Cadmium Contaminated Soils by Ferric Ion Modified Attapulgite (Fe/ATP)--Characterizations and Stabilization Mechanism].

    Science.gov (United States)

    Rong, Yang; Li, Rong-bo; Zhou, Yong-li; Chen, Jing; Wang, Lin-ling; Lu, Xiao-hua

    2015-08-01

    Ferric ion modified attapulgite (Fe/ATP) was prepared by impregnation and its structure and morphology were characterized. The toxicity characteristic leaching procedure (TCLP) was used to evaluate the effect of Cadmium( Cd) stabilization in soil with the addition of attapulgite (ATP) and Fe/ATP. The stabilization mechanism of Cd was further elucidated by comparing the morphologies and structure of ATP and Fe/ATP before and after Cd adsorption. Fe/ATP exhibited much better adsorption capacity than ATP, suggesting different adsorption mechanisms occurred between ATP and Fe/ATP. The leaching concentrations of Cd in soil decreased by 45% and 91% respectively, with the addition of wt. 20% ATP and Fe/ATP. The former was attributed to the interaction between Cd2 and --OH groups by chemical binding to form inner-sphere complexes in ATP and the attachment between Cd2+ and the defect sites in ATP framework. Whereas Cd stabilization with Fe/ATP was resulted from the fact that the active centers (--OH bonds or O- sites) on ATP could react with Fe3+ giving Fe--O--Cd-- bridges, which helped stabilize Cd in surface soil. What'more, the ferric oxides and metal hydroxides on the surface of ATP could interact with Cd, probably by the formation of cadmium ferrite. In conclusion, Fe/ATP, which can be easily prepared, holds promise as a potential low-cost and environmental friendly stabilizing agent for remediation of soil contaminated with heavy metals.

  7. Evaluation of ATP measurements to detect microbial ingress by wastewater and surface water in drinking water.

    Science.gov (United States)

    Vang, Óluva K; Corfitzen, Charlotte B; Smith, Christian; Albrechtsen, Hans-Jørgen

    2014-11-01

    Fast and reliable methods are required for monitoring of microbial drinking water quality in order to protect public health. Adenosine triphosphate (ATP) was investigated as a potential real-time parameter for detecting microbial ingress in drinking water contaminated with wastewater or surface water. To investigate the ability of the ATP assay in detecting different contamination types, the contaminant was diluted with non-chlorinated drinking water. Wastewater, diluted at 10(4) in drinking water, was detected with the ATP assay, as well as 10(2) to 10(3) times diluted surface water. To improve the performance of the ATP assay in detecting microbial ingress in drinking water, different approaches were investigated, i.e. quantifying microbial ATP or applying reagents of different sensitivities to reduce measurement variations; however, none of these approaches contributed significantly in this respect. Compared to traditional microbiological methods, the ATP assay could detect wastewater and surface water in drinking water to a higher degree than total direct counts (TDCs), while both heterotrophic plate counts (HPC 22 °C and HPC 37 °C) and Colilert-18 (Escherichia coli and coliforms) were more sensitive than the ATP measurements, though with much longer response times. Continuous sampling combined with ATP measurements displays definite monitoring potential for microbial drinking water quality, since microbial ingress in drinking water can be detected in real-time with ATP measurements. The ability of the ATP assay to detect microbial ingress is influenced by both the ATP load from the contaminant itself and the ATP concentration in the specific drinking water. Consequently, a low ATP concentration of the specific drinking water facilitates a better detection of a potential contamination of the water supply with the ATP assay. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Modulation of nucleotide sensitivity of ATP-sensitive potassium channels by phosphatidylinositol-4-phosphate 5-kinase.

    Science.gov (United States)

    Shyng, S L; Barbieri, A; Gumusboga, A; Cukras, C; Pike, L; Davis, J N; Stahl, P D; Nichols, C G

    2000-01-18

    ATP-sensitive potassium channels (K(ATP) channels) regulate cell excitability in response to metabolic changes. K(ATP) channels are formed as a complex of a sulfonylurea receptor (SURx), a member of the ATP-binding cassette protein family, and an inward rectifier K(+) channel subunit (Kir6.x). Membrane phospholipids, in particular phosphatidylinositol (PI) 4,5-bisphosphate (PIP(2)), activate K(ATP) channels and antagonize ATP inhibition of K(ATP) channels when applied to inside-out membrane patches. To examine the physiological relevance of this regulatory mechanism, we manipulated membrane PIP(2) levels by expressing either the wild-type or an inactive form of PI-4-phosphate 5-kinase (PIP5K) in COSm6 cells and examined the ATP sensitivity of coexpressed K(ATP) channels. Channels from cells expressing the wild-type PIP5K have a 6-fold lower ATP sensitivity (K(1/2), the half maximal inhibitory concentration, approximately 60 microM) than the sensitivities from control cells (K(1/2) approximately 10 microM). An inactive form of the PIP5K had little effect on the K(1/2) of wild-type channels but increased the ATP-sensitivity of a mutant K(ATP) channel that has an intrinsically lower ATP sensitivity (from K(1/2) approximately 450 microM to K(1/2) approximately 100 microM), suggesting a decrease in membrane PIP(2) levels as a consequence of a dominant-negative effect of the inactive PIP5K. These results show that PIP5K activity, which regulates PIP(2) and PI-3,4,5-P(3) levels, is a significant determinant of the physiological nucleotide sensitivity of K(ATP) channels.

  9. Excessive extracellular ATP desensitizes P2Y2 and P2X4 ATP receptors provoking surfactant impairment ending in ventilation-induced lung injury

    NARCIS (Netherlands)

    D. Hasan (Djo); Satalin, J. (Joshua); van der Zee, P. (Philip); Kollisch-Singule, M. (Michaela); P. Blankman (Paul); Shono, A. (Atsuko); P. Somhorst (Peter); C.A. den Uil (Corstiaan); H.J. Meeder (Han); Kotani, T. (Toru); G.F. Nieman (Gary F.)

    2018-01-01

    textabstractStretching the alveolar epithelial type I (AT I) cells controls the intercellular signaling for the exocytosis of surfactant by the AT II cells through the extracellular release of adenosine triphosphate (ATP) (purinergic signaling). Extracellular ATP is cleared by extracellular ATPases,

  10. Local release of ATP into the arterial inflow and venous drainage of human skeletal muscle: insight from ATP determination with the intravascular microdialysis technique

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Thaning, Pia; Nyberg, Michael Permin

    2011-01-01

    is released into plasma, we measured plasma [ATP] with the intravascular microdialysis technique at rest and during dynamic exercise (normoxia and hypoxia), passive exercise, thigh compressions and arterial ATP, tyramine and ACh infusion in a total of 16 healthy young men. Femoral arterial and venous...

  11. Critical role of γ-phosphate in structural transition of Na,K-ATPase upon ATP binding

    Science.gov (United States)

    Petrushanko, Irina Yu.; Mitkevich, Vladimir A.; Anashkina, Anastasia A.; Klimanova, Elizaveta A.; Dergousova, Elena A.; Lopina, Olga D.; Makarov, Alexander A.

    2014-06-01

    Active transport of sodium and potassium ions by Na,K-ATPase is accompanied by the enzyme conformational transition between E1 and E2 states. ATP and ADP bind to Na,K-ATPase in the E1 conformation with similar affinity but the properties of enzyme in complexes with these nucleotides are different. We have studied thermodynamics of Na,K-ATPase binding with adenine nucleotides at different temperatures using isothermal titration calorimetry. Our data indicate that β-phosphate is involved in complex formation by increasing the affinity of adenine nucleotides to Na,K-ATPase by an order of magnitude, while γ-phosphate does not affect it. ATP binding to Na,K-ATPase in contrast to ADP binding generates a structural transition in the enzyme, which is consistent with the movement of a significant portion of the surface area to a solvent-protected state. We propose that ATP binding leads to convergence of the nucleotide-binding and phosphorylation domains transferring the enzyme from the ``E1-open'' to ``E1-closed'' conformation ready for phosphorylation.

  12. Environmental Assessment for Selection and Operation of the Proposed Field Research Centers for the Natural and Accelerated Bioremediation Research (NABIR) Program

    International Nuclear Information System (INIS)

    2000-01-01

    The US Department of Energy (DOE) Office of Biological and Environmental Research (OBER), within the Office of Science (SC), proposes to add a Field Research Center (FRC) component to the existing Natural and Accelerated Bioremediation Research (NABIR) Program. The NABIR Program is a ten-year fundamental research program designed to increase the understanding of fundamental biogeochemical processes that would allow the use of bioremediation approaches for cleaning up DOE's contaminated legacy waste sites. An FRC would be integrated with the existing and future laboratory and field research and would provide a means of examining the fundamental biogeochemical processes that influence bioremediation under controlled small-scale field conditions. The NABIR Program would continue to perform fundamental research that might lead to promising bioremediation technologies that could be demonstrated by other means in the future. For over 50 years, DOE and its predecessor agencies have been responsible for the research, design, and production of nuclear weapons, as well as other energy-related research and development efforts. DOE's weapons production and research activities generated hazardous, mixed, and radioactive waste products. Past disposal practices have led to the contamination of soils, sediments, and groundwater with complex and exotic mixtures of compounds. This contamination and its associated costs and risks represents a major concern to DOE and the public. The high costs, long duration, and technical challenges associated with remediating the subsurface contamination at DOE sites present a significant need for fundamental research in the biological, chemical, and physical sciences that will contribute to new and cost-effective solutions. One possible low-cost approach for remediating the subsurface contamination of DOE sites is through the use of a technology known as bioremediation. Bioremediation has been defined as the use of microorganisms to biodegrade or

  13. Environmental Assessment for Selection and Operation of the Proposed Field Research Centers for the Natural and Accelerated Bioremediation Research (NABIR) Program

    Energy Technology Data Exchange (ETDEWEB)

    N/A

    2000-04-18

    The US Department of Energy (DOE) Office of Biological and Environmental Research (OBER), within the Office of Science (SC), proposes to add a Field Research Center (FRC) component to the existing Natural and Accelerated Bioremediation Research (NABIR) Program. The NABIR Program is a ten-year fundamental research program designed to increase the understanding of fundamental biogeochemical processes that would allow the use of bioremediation approaches for cleaning up DOE's contaminated legacy waste sites. An FRC would be integrated with the existing and future laboratory and field research and would provide a means of examining the fundamental biogeochemical processes that influence bioremediation under controlled small-scale field conditions. The NABIR Program would continue to perform fundamental research that might lead to promising bioremediation technologies that could be demonstrated by other means in the future. For over 50 years, DOE and its predecessor agencies have been responsible for the research, design, and production of nuclear weapons, as well as other energy-related research and development efforts. DOE's weapons production and research activities generated hazardous, mixed, and radioactive waste products. Past disposal practices have led to the contamination of soils, sediments, and groundwater with complex and exotic mixtures of compounds. This contamination and its associated costs and risks represents a major concern to DOE and the public. The high costs, long duration, and technical challenges associated with remediating the subsurface contamination at DOE sites present a significant need for fundamental research in the biological, chemical, and physical sciences that will contribute to new and cost-effective solutions. One possible low-cost approach for remediating the subsurface contamination of DOE sites is through the use of a technology known as bioremediation. Bioremediation has been defined as the use of microorganisms to

  14. Air-Stimulated ATP Release from Keratinocytes Occurs through Connexin Hemichannels

    Science.gov (United States)

    Barr, Travis P.; Albrecht, Phillip J.; Hou, Quanzhi; Mongin, Alexander A.; Strichartz, Gary R.; Rice, Frank L.

    2013-01-01

    Cutaneous ATP release plays an important role in both epidermal stratification and chronic pain, but little is known about ATP release mechanisms in keratinocytes that comprise the epidermis. In this study, we analyzed ATP release from cultured human neonatal keratinocytes briefly exposed to air, a process previously demonstrated to trigger ATP release from these cells. We show that exposing keratinocytes to air by removing media for 15 seconds causes a robust, long-lasting ATP release. This air-stimulated ATP release was increased in calcium differentiated cultures which showed a corresponding increase in connexin 43 mRNA, a major component of keratinocyte hemichannels. The known connexin hemichannel inhibitors 1-octanol and carbenoxolone both significantly reduced air-stimulated ATP release, as did two drugs traditionally used as ABC transporter inhibitors (glibenclamide and verapamil). These same 4 inhibitors also prevented an increase in the uptake of a connexin permeable dye induced by air exposure, confirming that connexin hemichannels are open during air-stimulated ATP release. In contrast, activity of the MDR1 ABC transporter was reduced by air exposure and the drugs that inhibited air-stimulated ATP release had differential effects on this transporter. These results indicate that air exposure elicits non-vesicular release of ATP from keratinocytes through connexin hemichannels and that drugs used to target connexin hemichannels and ABC transporters may cross-inhibit. Connexins represent a novel, peripheral target for the treatment of chronic pain and dermatological disease. PMID:23457608

  15. Membrane-associated proteolytic activity in Escherichia coli that is stimulated by ATP

    International Nuclear Information System (INIS)

    Klemes, Y.; Voellmy, R.W.; Goldberg, A.L.

    1986-01-01

    The degradation of proteins in bacteria requires metabolism energy. One important enzyme in this process is protease La, a soluble ATP-dependent protease encoded by the lon gene. However, lon mutants that lack a functional protease La still show some ATP-dependent protein breakdown. The authors have reported an ATP-stimulated endoproteolytic activity associated with the inner membrane of E. coli. This ATP-stimulated activity is found in normal levels in membranes derived from lon mutants, including strains carrying insertions in the lon gene. The membrane-bound activity hydrolyzes 14 C-methylglobin at a linear rate for up to 3 hours. These fractions also contain appreciable proteolytic activity that is not affected by ATP. The stimulation by ATP requires the presence of Mg 2+ . Nonhydrolyzable ATP analogs (e.g. AMPPNP or ATP-γ-S) and ADP do not enhance proteolysis. Unlike protease La, the membrane-associated enzyme does not degrade the fluorometric substrate, Glt-Ala-Ala-Phe-MNA, in an ATP-stimulated fashion, and its level is not influenced by high temperature of by the gene which regulates the heat-shock response. The enzyme is inhibited by dichloroisocoumarin and certain peptide chloromethyl ketones. They conclude that E. coli contain at least two ATP-dependent proteases with distinct specificities: one is soluble and the other is membrane-associated

  16. 78 FR 68111 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing of Proposed Rule Change, as...

    Science.gov (United States)

    2013-11-13

    ... entered by ATP Holders. \\7\\ Under Rules 980NY(c)(i)-(iii), incoming orders or quotes, or those residing in... ATP Holder During the Trading Day November 6, 2013. Pursuant to Section 19(b)(1) of the Securities... (``Commission'') the proposed rule change as described in Items I, II, and III below, which Items have been...

  17. 78 FR 12123 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing of Proposed Rule Change Amending...

    Science.gov (United States)

    2013-02-21

    ... in Items I, II, and III below, which Items have been prepared by the self-regulatory organization... Exchange proposes to amend the times in which certain ATP Holders are required to notify the Exchange in... to extend the time ATP Holders acting as agent for Customer orders have to notify the Exchange of a...

  18. 75 FR 17457 - Self-Regulatory Organizations; NYSE Amex LLC; Order Granting Accelerated Approval of the Proposed...

    Science.gov (United States)

    2010-04-06

    ...--Trading Systems), 964.2NY(b)(1)(iii) (Participation Entitlement of Specialists and e-Specialists), 964.2NY... protection. The proposal requires ATP holders to indicate whether Customer orders are ``Professional Customer'' orders.\\5\\ To comply with this requirement, ATP holders would be required to review their customers...

  19. Hda Monomerization by ADP Binding Promotes Replicase Clamp-mediated DnaA-ATP Hydrolysis*S⃞

    Science.gov (United States)

    Su'etsugu, Masayuki; Nakamura, Kenta; Keyamura, Kenji; Kudo, Yuka; Katayama, Tsutomu

    2008-01-01

    ATP-DnaA is the initiator of chromosomal replication in Escherichia coli, and the activity of DnaA is regulated by the regulatory inactivation of the DnaA (RIDA) system. In this system, the Hda protein promotes DnaA-ATP hydrolysis to produce inactive ADP-DnaA in a mechanism that is mediated by the DNA-loaded form of the replicase sliding clamp. In this study, we first revealed that hda translation uses an unusual initiation codon, CUG, located downstream of the annotated initiation codon. The CUG initiation codon could be used for restricting the Hda level, as this initiation codon has a low translation efficiency, and the cellular Hda level is only ∼100 molecules per cell. Hda translated using the correct reading frame was purified and found to have a high RIDA activity in vitro. Moreover, we found that Hda has a high affinity for ADP but not for other nucleotides, including ATP. ADP-Hda was active in the RIDA system in vitro and stable in a monomeric state, whereas apo-Hda formed inactive homomultimers. Both ADP-Hda and apo-Hda could form complexes with the DNA-loaded clamp; however, only ADP-Hda-DNA-clamp complexes were highly functional in the following interaction with DnaA. Formation of ADP-Hda was also observed in vivo, and mutant analysis suggested that ADP binding is crucial for cellular Hda activity. Thus, we propose that ADP is a crucial Hda ligand that promotes the activated conformation of the protein. ADP-dependent monomerization might enable the arginine finger of the Hda AAA+ domain to be accessible to ATP bound to the DnaA AAA+ domain. PMID:18977760

  20. Optimum ratio of AET, ATP and serotonin applied in combinations determined with a reference to their toxicity

    International Nuclear Information System (INIS)

    Benova, D.K.; P''tev, I.Kh.

    1985-01-01

    In experiments on mice, a study was made of the quantitative dependence of toxicity of AET, ATP and serotonin applied in combinations. The toxicity decreased when ATP was combined with AET and increased when ATP of AET were combined with serotonin. The toxicity of a combination of all three substances was reduced by introducing high doses of ATP

  1. Bcl-2 protects against apoptosis induced by antimycin A and bongkrekic acid without restoring cellular ATP levels.

    NARCIS (Netherlands)

    Graaf, A.O. de; Meijerink, J.P.P.; Heuvel, L.P.W.J. van den; Abreu, R.A. de; Witte, T.J.M. de; Jansen, J.H.; Smeitink, J.A.M.

    2002-01-01

    Several studies indicate that mitochondrial ATP production as well as ADP/ATP exchange across mitochondrial membranes are impaired during apoptosis. We investigated whether Bcl-2 could protect against cell death under conditions in which ATP metabolism is inhibited. Inhibition of ATP production

  2. A divergent ADP/ATP carrier in the hydrogenosomes of Trichomonas gallinae argues for an independent origin of these organelles.

    NARCIS (Netherlands)

    Tjaden, J.; Haferkamp, I.; Boxma, B.; Tielens, A.G.; Huynen, M.A.; Hackstein, J.H.P.

    2004-01-01

    The evolution of mitochondrial ADP and ATP exchanging proteins (AACs) highlights a key event in the evolution of the eukaryotic cell, as ATP exporting carriers were indispensable in establishing the role of mitochondria as ATP-generating cellular organelles. Hydrogenosomes, i.e. ATP- and

  3. PROPUESTA PARA EL DESARROLLO DE INSTRUMENTOS DE AUTOEVALUACIÓN PARA PROGRAMAS EDUCATIVOS A DISTANCIA (PROPOSAL FOR THE DEVELOPMENT OF SELF-ASSESSMENT INSTRUMENTS FOR DISTANCE EDUCATION PROGRAMS

    Directory of Open Access Journals (Sweden)

    García Martínez Verónica

    2011-08-01

    Full Text Available Resumen:El presente trabajo expone la etapa inicial de un proyecto conjunto entre la Universidad Juárez Autónoma de Tabasco (UJAT y la Universidad Autónoma de Chiapas (UNACH, México; se trata de una estrategia diseñada para elaborar mecanismos que permitan a los programas virtuales autoevaluarse. La propuesta surge como resultado de la aplicación de un modelo de autoevaluación de programas a distancia diseñado por la Asociación Nacional de Universidades e Instituciones de Educación Superior (ANUIES y tomado como referencia para instrumentar en la UJAT, un ejercicio de autodiagnóstico durante el periodo 2008-2009. Los resultados mostraron la necesidad de pensar en mecanismos de evaluación situados en el contexto regional. La propuesta descansa, principalmente, en la revisión documental y en el panel de expertos elegidos mediante el método Delphi y Método combinado TZ. La estrategia metodológica consta de cuatro etapas: a revisión de modelos de evaluación; b la selección de expertos de dos universidades de los Estados de Tabasco y Chiapas que cuentan desde hace más de diez años con programas virtuales; c el diseño de instrumentos de auto diagnóstico y d la calificación de los instrumentos por los expertos. El reporte describe tres de las cuatro etapas del estudio. El promedio del índice de expertos en la autoevaluación fue similar en las dos universidades; se concluye, por lo tanto, que los expertos comparten un nivel de conocimiento afín, en especial en el diseño de materiales u objetos de aprendizaje, no así en indicadores de calidad estimados para la educación virtual.Abstract: The present study describes the initial stage of a joint project between the Universidad Juárez Autónoma de Tabasco (UJAT y the Universidad Autónoma de Chiapas (UNACH México. This is a strategy designed to develop mechanisms to let the distance learning programs to self - assessment. The proposal is the result of applying a self

  4. Propuesta de una guía de autoevaluación para programas de posgrado Proposal of a self-evaluation guide for postgraduate programs

    Directory of Open Access Journals (Sweden)

    Rosalba Roque González

    2010-03-01

    Full Text Available En la actualidad el mejoramiento de la calidad de los programas de posgrado es una prioridad para las universidades y los centros de posgrado que se encargan de la formación integral de los educandos y el perfeccionamiento de su competencia y desempeño. Se diseñó una guía de autoevaluación para medir la calidad de la impartición de los programas de posgrado que se realizan en el Centro de Estudios de Posgrado de Cirugía de Mínimo Acceso, de La Habana. La consulta a expertos y el análisis de contenido permitió seleccionar las variables cualitativas, los criterios y la ponderación que se utilizarían para la confección de la guía. La propuesta presentada es novedosa, por cuanto en el centro no existe un instrumento que permita valorar la calidad de la superación profesional, la experiencia institucional y del claustro profesoral para el perfeccionamiento de los recursos humanos.Nowadays the improvement of postgraduate programs quality is as priority for universities and postgraduate center to be in charge of student integral training and the improvement of its competence and performance. A self-evaluation guide was designed to measure the teaching the postgraduate programs in the Center of Postgraduate Studies on Minimal-Access Surgery of The Habana City. The experts consultation and the content analysis allowed us to select the qualitative variables, criteria and weighting used for designing of this guide. This proposal is novel, but in our center it is not available a tool allowing to value the professional training quality, the institutional experience and the educational staff for the improvement of human resources.

  5. C-terminus of the P4-ATPase ATP8A2 functions in protein folding and regulation of phospholipid flippase activity.

    Science.gov (United States)

    Chalat, Madhavan; Moleschi, Kody; Molday, Robert S

    2017-02-01

    ATP8A2 is a P4-ATPase that flips phosphatidylserine and phosphatidylethanolamine across cell membranes. This generates membrane phospholipid asymmetry, a property important in many cellular processes, including vesicle trafficking. ATP8A2 deficiency causes severe neurodegenerative diseases. We investigated the role of the C-terminus of ATP8A2 in its expression, subcellular localization, interaction with its subunit CDC50A, and function as a phosphatidylserine flippase. C-terminal deletion mutants exhibited a reduced tendency to solubilize in mild detergent and exit the endoplasmic reticulum. The solubilized protein, however, assembled with CDC50A and displayed phosphatidylserine flippase activity. Deletion of the C-terminal 33 residues resulted in reduced phosphatidylserine-dependent ATPase activity, phosphatidylserine flippase activity, and neurite extension in PC12 cells. These reduced activities were reversed with 60- and 80-residue C-terminal deletions. Unlike the yeast P4-ATPase Drs2, ATP8A2 is not regulated by phosphoinositides but undergoes phosphorylation on the serine residue within a CaMKII target motif. We propose a model in which the C-terminus of ATP8A2 consists of an autoinhibitor domain upstream of the C-terminal 33 residues and an anti-autoinhibitor domain at the extreme C-terminus. The latter blocks the inhibitory activity of the autoinhibitor domain. We conclude that the C-terminus plays an important role in the efficient folding and regulation of ATP8A2. © 2017 Chalat et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  6. Prevalence of the metabolic syndrome in Pudong New Area of Shanghai using three proposed definitions among Chinese adults

    Directory of Open Access Journals (Sweden)

    Jiang Qing-wu

    2010-05-01

    Full Text Available Abstract Background The prevalence of metabolic syndrome (MS has been increasing in China in recent years. The aim of this study is to estimate and compare the prevalence of MS among Chinese adults in Shanghai, one of the most economic developed areas in China, using definitions proposed by World Health Organization (WHO, National Cholesterol Education Program Adult Treatment Panel (modified ATP III and International Diabetes Federation (IDF. Methods This cross-sectional study included 5,584 adults at age 20-79 randomly selected from Pudong New Area of Shanghai, China, through a three-stage sampling. All participants were interviewed in-person between April and July of 2008 to collect information on demographic and lifestyle characteristics. At the interview, anthropometry and blood pressure were measured and bio-specimens were collected. Results The prevalence estimates for the MS increased with age for each definition in men and women, but the estimates varied greatly between the definitions and by sex. The prevalence of the MS was higher in men (20.2% than in women (18.7% using WHO definition but this sex difference was reversed when using the modified ATP III (28.4% for men vs. 35.1% for women and the IDF (15.9% for men vs. 26.7% for women criteria. The most common metabolic disorder in this population was dyslipidaemia, regardless of the definition used. Substantial agreement, estimated using the kappa statistic, was found between the modified ATP III and IDF definition, whereas the lowest agreement was observed between the WHO and ATP III criteria. Conclusions The MS is highly prevalent among Chinese adults in Pudong New Area of Shanghai and the most prevalent component was dyslipidemia. These findings underscore the importance of prevention and control efforts for the MS in this area and the need for a unified predictive definition for the syndrome for use by clinical practitioners and public health agencies.

  7. Gamma-radiation effect of the ATP-ASE-activity in various parts of cotton sprouts

    International Nuclear Information System (INIS)

    Kazimov, A.K.

    1975-01-01

    ATP-ase is a thiol enzyme whose sulfhydryl group plays an important role. The transport of substances through biological membranes is the result of the action of the sodium-potassium pump of the cell, which functions with ATP energy. The action of this transport mechanism depends on the activity of ATP-ase. It may be postulated, therefore, that the suppression of the active transport of Na + and K + ions in cells under irradiation is partially the result of a disturbance of the activity of the ATP enzyme system. The author studied the effect of gamma radiation on ATP-ase activity in various parts of seven-day-old seedlings of type 108-F cotton, which were irradiated using Co 60 gamma radiation. The results of the experiment showed that the ATP-ase activity of the cotton seedling rootlets depends on the dose and the time elapsed after irradiation (a table is given). Small radiation doses (0.2 and 0.5 krad) significantly increased ATP-ase activity in the rootlets, while heavy doses inhibited it significantly. Similar results were obtained for the stems and leaves (tables are given). It was estblished that the ATP-ase of cotton seedlings has varying sensitivity to irradiation. The most sensitive ATP-ases were those of the rootlets. The activity of background ATP-ase is less subject to change than Na + and K + activated ATP-ases. For example, while the activity of ATP-ase (without ions) was inhibited by 25% when a 25 krad irradiation dose was administered, the retardation of Na + and K + activated ATP-ases reached 41%. The author suggests that the inhibition of ATP-ase activity under irradiation is mainly the result of a disturbance of the structure of the membrane functions. It is also possible that ATP-ase activity decreases because of a lack of the enzyme substrate - ATP, which is formed during the process of oxydative phosphorylization. A table is also provided showing the effect of irradiation on the activity of ATP-ase activated by various ions in the roots of

  8. The proposed human factors engineering program plan for man-machine interface system design of the next generation NPP in Korea

    International Nuclear Information System (INIS)

    Oh, I.S.; Lee, H.C.; Seo, S.M.; Cheon, S.W.; Park, K.O.; Lee, J.W.; Sim, B.S.

    1994-01-01

    Human factors application to nuclear power plant (NPP) design, especially, to man-machine interface system (MMIS) design becomes an important issue among the licensing requirements. Recently, the nuclear regulatory bodies require the evidence of systematic human factors application to the MMIS design. Human Factors Engineering Program Plan (HFEPP), as a basis and central one among the human factors application by the MMIS designers. This paper describes the framework of HFEPP for the MMIS design of next generation NPP (NG-NPP) in Korea. This framework provides an integral plan and some bases of the systematic application of human factors to the MMIS design, and consists of purpose and scope, codes and standards, human factors organization, human factors tasks, engineering control methodology, human factors documentations, and milestones. The proposed HFEPP is a top level document to define and describe human factors tasks, based on each step of MMIS design process, in view point of how, what, when and by whom to be performed. (author). 11 refs, 1 fig

  9. Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Al-Khazraji, Baraa K; Mortensen, Stefan P

    2013-01-01

    During skeletal muscle contractions, the concentration of ATP increases in muscle interstitial fluid as measured by microdialysis probes. This increase is associated with the magnitude of blood flow, suggesting that interstitial ATP may be important for contraction-induced vasodilation. However...... studied. The rat gluteus maximus skeletal muscle model was used to study changes in local skeletal muscle hemodynamics. Superfused ATP at concentrations found during muscle contractions (1-10 µM) increased blood flow by up to 400%. In this model, the underlying mechanism was also examined by inhibition...... in interstitial ATP concentrations increases muscle blood flow, indicating that the contraction-induced increase in skeletal muscle interstitial [ATP] is important for exercise hyperemia. The vasodilator effect of ATP application is mediated by NO and prostanoid formation....

  10. ATP secretion from nerve trunks and Schwann cells mediated by glutamate.

    Science.gov (United States)

    Liu, Guo Jun; Bennett, Max R

    2003-11-14

    ATP release from rat sciatic nerves and from cultured Schwann cells isolated from the nerves was investigated using an online bioluminescence technique. ATP was released in relatively large amounts from rat sciatic nerve trunks during electrical stimulation. This release was blocked by the sodium channel inhibitor tetrodotoxin and the non-NMDA glutamate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Schwann cells isolated from the nerve trunks did not release ATP when electrically stimulated but did in response to glutamate in a concentration-dependent manner. Glutamate-stimulated ATP release was inhibited by specific non-competitive AMPA receptor antagonist GYKI 52466 and competitive non-NMDA receptor antagonist CNQX. Glutamate-stimulated ATP release was decreased by inhibition of anion transporter inhibitors by furosemide, cystic fibrosis transmembrane conductance regulator by glibenclamide and exocytosis by botulinum toxin A, indicating that anion transporters and exocytosis provide the main secretion mechanisms for ATP release from the Schwann cells.

  11. Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Pitceathly, Robert D S

    2012-09-11

    Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting 1 in 2,500 individuals. Mitochondrial DNA (mtDNA) mutations are not generally considered within the differential diagnosis of patients with uncomplicated inherited neuropathy, despite the essential requirement of ATP for axonal function. We identified the mtDNA mutation m.9185T>C in MT-ATP6, encoding the ATP6 subunit of the mitochondrial ATP synthase (OXPHOS complex V), at homoplasmic levels in a family with mitochondrial disease in whom a severe motor axonal neuropathy was a striking feature. This led us to hypothesize that mutations in the 2 mtDNA complex V subunit encoding genes, MT-ATP6 and MT-ATP8, might be an unrecognized cause of isolated axonal CMT and distal hereditary motor neuropathy (dHMN).

  12. Facile conversion of ATP-binding RNA aptamer to quencher-free molecular aptamer beacon.

    Science.gov (United States)

    Park, Yoojin; Nim-Anussornkul, Duangrat; Vilaivan, Tirayut; Morii, Takashi; Kim, Byeang Hyean

    2018-01-15

    We have developed RNA-based quencher-free molecular aptamer beacons (RNA-based QF-MABs) for the detection of ATP, taking advantage of the conformational changes associated with ATP binding to the ATP-binding RNA aptamer. The RNA aptamer, with its well-defined structure, was readily converted to the fluorescence sensors by incorporating a fluorophore into the loop region of the hairpin structure. These RNA-based QF-MABs exhibited fluorescence signals in the presence of ATP relative to their low background signals in the absence of ATP. The fluorescence emission intensity increased upon formation of a RNA-based QF-MAB·ATP complex. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Methodological problems of direct bioluminescent ATP assay in platelets and erythrocytes.

    Science.gov (United States)

    Girotti, S; Ferri, E; Cascione, M L; Comuzio, S; Mazzuca, A; Orlandini, A; Breccia, A

    1989-07-01

    Direct bioluminescent ATP determination in platelets and erythrocytes involves the study of different parameters which are discussed here. Some parameters are linked to the bioluminescent reaction and to the analyte (ATP); others have regard to the biological matrix. The composition of bioluminescent reagents and the preparation and conservation of the ATP standard, also in the presence of excipients, are among the first given. Matrix problems involve cell characteristics related to age and form, lysis resistance and the possible formation of aggregates (platelets) that may inhibit the complete release of ATP. For these reasons we used the most efficient ATP release agent with the lowest inhibitory effect on luciferase. The data obtained correlate well with a bioluminescent method requiring extraction with ethanol/EDTA, and therefore more time, for ATP determination in platelets and erythrocytes.

  14. Antihypertrophic Effects of Small Molecules that Maintain Mitochondrial ATP Levels Under Hypoxia

    Directory of Open Access Journals (Sweden)

    Hiroaki Nagai

    2017-10-01

    Full Text Available Since impaired mitochondrial ATP production in cardiomyocytes is thought to lead to heart failure, a drug that protects mitochondria and improves ATP production under disease conditions would be an attractive treatment option. In this study, we identified small-molecule drugs, including the anti-parasitic agent, ivermectin, that maintain mitochondrial ATP levels under hypoxia in cardiomyocytes. Mechanistically, transcriptomic analysis and gene silencing experiments revealed that ivermectin increased mitochondrial ATP production by inducing Cox6a2, a subunit of the mitochondrial respiratory chain. Furthermore, ivermectin inhibited the hypertrophic response of human induced pluripotent stem cell-derived cardiomyocytes. Pharmacological inhibition of importin β, one of the targets of ivermectin, exhibited protection against mitochondrial ATP decline and cardiomyocyte hypertrophy. These findings indicate that maintaining mitochondrial ATP under hypoxia may prevent hypertrophy and improve cardiac function, providing therapeutic options for mitochondrial dysfunction.

  15. ATP synthesis is impaired in isolated mitochondria from myotubes established from type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Minet, Ariane D; Gaster, Michael

    2010-01-01

    To date, it is unknown whether mitochondrial dysfunction in skeletal muscle from subjects with type 2 diabetes is based on primarily reduced mitochondrial mass and/or a primarily decreased mitochondrial ATP synthesis. Mitochondrial mass were determined in myotubes established from eight lean, eight...... mass and the ATP synthesis rate, neither at baseline nor during acute insulin stimulation, were not different between groups. The ratio of ATP synthesis rate at hexokinase versus ATP synthesis rate at baseline was lower in diabetic mitochondria compared to lean mitochondria. Thus the lower content...... obese and eight subjects with type 2 diabetes precultured under normophysiological conditions. Furthermore, mitochondria were isolated and ATP production was measured by luminescence at baseline and during acute insulin stimulation with or without concomitant ATP utilization by hexokinase. Mitochondrial...

  16. ATP-loading 201Tl myocardial SPECT for the detection of ischemic heart disease

    International Nuclear Information System (INIS)

    Fujinaga, Tsuyoshi; Yamazaki, Sayaka; Hara, Masatada; Umezawa, Chiaki; Okamura, Tetsuo; Murata, Hajime; Maruno, Hirotaka; Onoguchi, Masahisa.

    1993-01-01

    To evaluate the usefulness for the detection of ischemic heart disease, ATP myocrdial SPECT was performed in 35 patients (mean; 59±9.4 years) with angina pectoris or old myocardial infarction. Coronary angiography (CAG) was performed in all patients. The ultra-short half-life of ATP required a continuous infusion for its use. ATP was infused intravenously at a rate of 0.16 mg/kg/min for 5 min, with 201 Tl injection taking place at 3 min. Myocardial SPECT imaging was begun 5 min and 4 hr later after the end of ATP infusion. ATP caused a significant decrease in arterial blood pressure (p 201 Tl myocardial SPECT for the detection of coronary artery disease (CAD) was evaluated using CAG as a golden standard. The sensitivity and specificity for CAD detection were 82% and 90%, respectively. ATP myocardial SPECT is a promising new test for the detection of ischemic heart disease. (author)

  17. Excessive Extracellular ATP Desensitizes P2Y2 and P2X4 ATP Receptors Provoking Surfactant Impairment Ending in Ventilation-Induced Lung Injury

    Directory of Open Access Journals (Sweden)

    Djo Hasan

    2018-04-01

    Full Text Available Stretching the alveolar epithelial type I (AT I cells controls the intercellular signaling for the exocytosis of surfactant by the AT II cells through the extracellular release of adenosine triphosphate (ATP (purinergic signaling. Extracellular ATP is cleared by extracellular ATPases, maintaining its homeostasis and enabling the lung to adapt the exocytosis of surfactant to the demand. Vigorous deformation of the AT I cells by high mechanical power ventilation causes a massive release of extracellular ATP beyond the clearance capacity of the extracellular ATPases. When extracellular ATP reaches levels >100 μM, the ATP receptors of the AT II cells become desensitized and surfactant impairment is initiated. The resulting alteration in viscoelastic properties and in alveolar opening and collapse time-constants leads to alveolar collapse and the redistribution of inspired air from the alveoli to the alveolar ducts, which become pathologically dilated. The collapsed alveoli connected to these dilated alveolar ducts are subject to a massive strain, exacerbating the ATP release. After reaching concentrations >300 μM extracellular ATP acts as a danger-associated molecular pattern, causing capillary leakage, alveolar space edema, and further deactivation of surfactant by serum proteins. Decreasing the tidal volume to 6 mL/kg or less at this stage cannot prevent further lung injury.

  18. An analysis of the CERCLA response program and the RCRA corrective action program in determining cleanup strategies for federal facilities which have been proposed for listing on the National Priorities List

    International Nuclear Information System (INIS)

    Baker, P.; Vinson, R.

    1994-01-01

    This document was prepared as an issue paper for the Department of Energy to serve in the decision-making process for environmental restoration activities. The paper compares cleanup requirements under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) and those currently proposed under Subpart S of the Resource Conservation and Recovery Act (RCRA). The history and regulatory framework for both laws is discussed, and the process for environmental restoration actions under both regulatory programs is compared and contrasted. Contaminants regulated under CERCLA and RCRA differ significantly in that radioactive contaminants are subject to Environmental Protection Agency jurisdiction only under CERCLA. The DOE has the jurisdiction to implement radioactive waste management and cleanup levels under the Atomic Energy Act (AEA) at nuclear weapons facilities. For sites with significant amounts of contaminants which are radioactive only, cleanup under RCRA can present significant advantages, since the DOE can then manage restoration activities under its own authority. There are, conversely several significant advantages for a remedial action being conducted at a CERCLA site recognized on the National Priorities List (NPL). Other provisions in the CERCLA remediation and the RCRA corrective action process offer both advantages and disadvantages related to DOE environmental restoration programs. This paper presents a discussion of significant issues which should be considered in such negotiations

  19. [Environmental Hazards Assessment Program annual report, June 1992--June 1993]. Needs assessment for the proposed masters degree program in environmental science at the Medical University of South Carolina: EHAP Volume 1, No. 2

    Energy Technology Data Exchange (ETDEWEB)

    Hoomani, J.

    1993-05-01

    There will be a critical shortage of professionals who are educated to deal with environmental problems by 1997. This was the major finding of a 1992 study conducted by the Oak Ridge Associated Universities, Incorporated and the Pacific Northwest Laboratory (Publication Number PAL-8171, CU-700). The study was done to determine the manpower needs of the Office of Environmental Restoration and Waste Management in the US Department of Energy (DOE). Although the focus of the study was the 19 sites of the DOE complex, including the Savannah River Site in South Carolina, the study documented that such shortages will affect other major agencies and organizations including the US Department of Interior, the US Department of Defense, the Environmental Protection Agency, state and local governmental agencies, private agencies, and manufacturing enterprises throughout the State of South Carolina and the National. The Oak Ridge Study also documented that a variety of professional positions requiring environmental expertise are difficult to fill because traditional educational programs in physical science, engineering, health science, public policy, and administration have not adequately responded to the unique nature of these emerging specialities. This lack of educational preparation has necessitated extensive on-site training of new employees before they can become productive members of the environmental work force. Unique educational initiatives such as the Environmental Studies program proposed here are vital to address the long-term demand for environmental professionals.

  20. 31P magnetization transfer measurements of Pi→ATP flux in exercising human muscle.

    Science.gov (United States)

    Sleigh, Alison; Savage, David B; Williams, Guy B; Porter, David; Carpenter, T Adrian; Brindle, Kevin M; Kemp, Graham J

    2016-03-15

    Fundamental criticisms have been made over the use of (31)P magnetic resonance spectroscopy (MRS) magnetization transfer estimates of inorganic phosphate (Pi)→ATP flux (VPi-ATP) in human resting skeletal muscle for assessing mitochondrial function. Although the discrepancy in the magnitude of VPi-ATP is now acknowledged, little is known about its metabolic determinants. Here we use a novel protocol to measure VPi-ATP in human exercising muscle for the first time. Steady-state VPi-ATP was measured at rest and over a range of exercise intensities and compared with suprabasal oxidative ATP synthesis rates estimated from the initial rates of postexercise phosphocreatine resynthesis (VATP). We define a surplus Pi→ATP flux as the difference between VPi-ATP and VATP. The coupled reactions catalyzed by the glycolytic enzymes GAPDH and phosphoglycerate kinase (PGK) have been shown to catalyze measurable exchange between ATP and Pi in some systems and have been suggested to be responsible for this surplus flux. Surplus VPi-ATP did not change between rest and exercise, even though the concentrations of Pi and ADP, which are substrates for GAPDH and PGK, respectively, increased as expected. However, involvement of these enzymes is suggested by correlations between absolute and surplus Pi→ATP flux, both at rest and during exercise, and the intensity of the phosphomonoester peak in the (31)P NMR spectrum. This peak includes contributions from sugar phosphates in the glycolytic pathway, and changes in its intensity may indicate changes in downstream glycolytic intermediates, including 3-phosphoglycerate, which has been shown to influence the exchange between ATP and Pi catalyzed by GAPDH and PGK. Copyright © 2016 the American Physiological Society.

  1. A new function for ATP: activating cardiac sympathetic afferents during myocardial ischemia.

    Science.gov (United States)

    Fu, Liang-Wu; Longhurst, John C

    2010-12-01

    Myocardial ischemia activates cardiac sympathetic afferents leading to chest pain and reflex cardiovascular responses. Brief myocardial ischemia leads to ATP release in the interstitial space. Furthermore, exogenous ATP and α,β-methylene ATP (α,β-meATP), a P2X receptor agonist, stimulate cutaneous group III and IV sensory nerve fibers. The present study tested the hypothesis that endogenous ATP excites cardiac afferents during ischemia through activation of P2 receptors. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicates (T(2)-T(5)) in anesthetized cats. Single fields of 45 afferents (conduction velocities = 0.25-4.92 m/s) were identified in the left ventricle with a stimulating electrode. Five minutes of myocardial ischemia stimulated 39 of 45 cardiac afferents (8 Aδ, 37 C fibers). Epicardial application of ATP (1-4 μmol) stimulated six ischemically sensitive cardiac afferents in a dose-dependent manner. Additionally, epicardial ATP (2 μmol), ADP (2 μmol), a P2Y agonist, and α,β-meATP (0.5 μmol) significantly activated eight other ischemically sensitive afferents. Third, pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid, a P2 receptor antagonist, abolished the responses of six afferents to epicardial ATP (2 μmol) and attenuated the ischemia-related increase in activity of seven other afferents by 37%. In the absence of P2 receptor blockade, cardiac afferents responded consistently to repeated application of ATP (n = 6) and to recurrent myocardial ischemia (n = 6). Finally, six ischemia-insensitive cardiac spinal afferents did not respond to epicardial ATP (2-4 μmol), although these afferents did respond to epicardial bradykinin. Taken together, these data indicate that, during ischemia, endogenously released ATP activates ischemia-sensitive, but not ischemia-insensitive, cardiac spinal afferents through stimulation of P2 receptors likely located on the cardiac sensory

  2. Role of connexin 32 hemichannels in the release of ATP from peripheral nerves.

    Science.gov (United States)

    Nualart-Marti, Anna; del Molino, Ezequiel Mas; Grandes, Xènia; Bahima, Laia; Martin-Satué, Mireia; Puchal, Rafel; Fasciani, Ilaria; González-Nieto, Daniel; Ziganshin, Bulat; Llobet, Artur; Barrio, Luis C; Solsona, Carles

    2013-12-01

    Extracellular purines elicit strong signals in the nervous system. Adenosine-5'-triphosphate (ATP) does not spontaneously cross the plasma membrane, and nervous cells secrete ATP by exocytosis or through plasma membrane proteins such as connexin hemichannels. Using a combination of imaging, luminescence and electrophysiological techniques, we explored the possibility that Connexin 32 (Cx32), expressed in Schwann cells (SCs) myelinating the peripheral nervous system could be an important source of ATP in peripheral nerves. We triggered the release of ATP in vivo from mice sciatic nerves by electrical stimulation and from cultured SCs by high extracellular potassium concentration-evoked depolarization. No ATP was detected in the extracellular media after treatment of the sciatic nerve with Octanol or Carbenoxolone, and ATP release was significantly inhibited after silencing Cx32 from SCs cultures. We investigated the permeability of Cx32 to ATP by expressing Cx32 hemichannels in Xenopus laevis oocytes. We found that ATP release is coupled to the inward tail current generated after the activation of Cx32 hemichannels by depolarization pulses, and it is sensitive to low extracellular calcium concentrations. Moreover, we found altered ATP release in mutated Cx32 hemichannels related to the X-linked form of Charcot-Marie-Tooth disease, suggesting that purinergic-mediated signaling in peripheral nerves could underlie the physiopathology of this neuropathy. Copyright © 2013 Wiley Periodicals, Inc.

  3. An ATP sensitive light addressable biosensor for extracellular monitoring of single taste receptor cell.

    Science.gov (United States)

    Wu, Chunsheng; Du, Liping; Zou, Ling; Zhao, Luhang; Wang, Ping

    2012-12-01

    Adenosine triphosphate (ATP) is considered as the key neurotransmitter in taste buds for taste signal transmission and processing. Measurements of ATP secreted from single taste receptor cell (TRC) with high sensitivity and specificity are essential for investigating mechanisms underlying taste cell-to-cell communications. In this study, we presented an aptamer-based biosensor for the detection of ATP locally secreted from single TRC. ATP sensitive DNA aptamer was used as recognition element and its DNA competitor was served as signal transduction element that was covalently immobilized on the surface of light addressable potentiometric sensor (LAPS). Due to the light addressable capability of LAPS, local ATP secretion from single TRC can be detected by monitoring the working potential shifts of LAPS. The results show this biosensor can detect ATP with high sensitivity and specificity. It is demonstrated this biosensor can effectively detect the local ATP secretion from single TRC responding to tastant mixture. This biosensor could provide a promising new tool for the research of taste cell-to-cell communications as well as for the detection of local ATP secretion from other types of ATP secreting individual cells.

  4. Multiscale approach to link red blood cell dynamics, shear viscosity, and ATP release.

    Science.gov (United States)

    Forsyth, Alison M; Wan, Jiandi; Owrutsky, Philip D; Abkarian, Manouk; Stone, Howard A

    2011-07-05

    RBCs are known to release ATP, which acts as a signaling molecule to cause dilation of blood vessels. A reduction in the release of ATP from RBCs has been linked to diseases such as type II diabetes and cystic fibrosis. Furthermore, reduced deformation of RBCs has been correlated with myocardial infarction and coronary heart disease. Because ATP release has been linked to cell deformation, we undertook a multiscale approach to understand the links between single RBC dynamics, ATP release, and macroscopic viscosity all at physiological shear rates. Our experimental approach included microfluidics, ATP measurements using a bioluminescent reaction, and rheology. Using microfluidics technology with high-speed imaging, we visualize the deformation and dynamics of single cells, which are known to undergo motions such as tumbling, swinging, tanktreading, and deformation. We report that shear thinning is not due to cellular deformation as previously believed, but rather it is due to the tumbling-to-tanktreading transition. In addition, our results indicate that ATP release is constant at shear stresses below a threshold (3 Pa), whereas above the threshold ATP release is increased and accompanied by large cellular deformations. Finally, performing experiments with well-known inhibitors, we show that the Pannexin 1 hemichannel is the main avenue for ATP release both above and below the threshold, whereas, the cystic fibrosis transmembrane conductance regulator only contributes to deformation-dependent ATP release above the stress threshold.

  5. Identification of a new Mpl-interacting protein, Atp5d.

    Science.gov (United States)

    Liu, Hongyan; Zhao, Zhenhu; Zhong, Yuxu; Shan, Yajun; Sun, Xiaohong; Mao, Bingzhi; Cong, Yuwen

    2014-06-01

    Thrombopoietin (TPO) can regulate hematopoiesis and megakaryopoiesis via activation of its receptor, c-Mpl, and multiple downstream signal transduction pathways. Using the cytoplasmic domain of Mpl as bait, we performed yeast two-hybrid screening, and found that the protein Atp5d might associate with Mpl. Atp5d is known as the δ subunit of mitochondrial ATP synthase, but little is known about the function of dissociative Atp5d. The interaction between Mpl and Atp5d was confirmed by the yeast two-hybrid system, mammalian two-hybrid assay, pull-down experiment, and co-immunoprecipitation study in vivo and in vitro. An additional immunofluorescence assay showed that the two proteins can colocalize along the plasma membrane in the cytoplasm. Using the yeast two-hybrid system, we tested a series of cytoplasmic truncated mutations for their ability to bind Atp5d and found an association between Atp5d and the Aa98-113 domain of Mpl. The dissociation of Atp5d from Mpl after TPO stimulation suggests that Atp5d may be a new component of TPO signaling.

  6. ATP-containing vesicles in stria vascular marginal cell cytoplasms in neonatal rat cochlea are lysosomes.

    Science.gov (United States)

    Liu, Jun; Liu, Wenjing; Yang, Jun

    2016-02-11

    We confirmed that ATP is released from cochlear marginal cells in the stria vascular but the cell organelle in which ATP stores was not identified until now. Thus, we studied the ATP-containing cell organelles and suggest that these are lysosomes. Primary cultures of marginal cells of Sprague-Dawley rats aged 1-3 days was established. Vesicles within marginal cells stained with markers were identified under confocal laser scanning microscope and transmission electron microscope (TEM). Then ATP release from marginal cells was measured after glycyl-L-phenylalanine-ß- naphthylamide (GPN) treatment using a bioluminescent assay. Quinacrine-stained granules within marginal cells were labeled with LysoTracker, a lysosome tracer, and lysosomal-associated membrane protein 1(LAMP1), but not labeled with the mitochondrial tracer MitoTracker. Furthermore, LysoTracker-labelled puncta showed accumulation of Mant-ATP, an ATP analog. Treatment with 200 μM GPN quenched fluorescently labeled puncta after incubation with LysoTracker or quinacrine, but not MitoTracker. Quinacrine-labeled organelles observed by TEM were lysosomes, and an average 27.7 percent increase in ATP luminescence was observed in marginal cells extracellular fluid after GPN treatment. ATP-containing vesicles in cochlear marginal cells of the stria vascular from neonatal rats are likely lysosomes. ATP release from marginal cells may be via Ca(2+)-dependent lysosomal exocytosis.

  7. Towards the development of an automated ATP measuring platform to monitor microbial quality of drinking water

    DEFF Research Database (Denmark)

    Tatari, Karolina; Hansen, C. B.; Rasmussen, A.

    is detected by a photomultiplier. Temperature in the assay box is controlled and set to 25°C. Calibration of the system using ATP standard solutions was successful, both for free and for total ATP. Chemical release of ATP by reagent addition however resulted in the formation of particles that ultimately......This work aimed to develop an automated and nearly on-line method to monitor ATP levels in drinking water as an indicator of microbial contamination. The system consists of a microfluidic cartridge installed in a light tight box, where the sample is mixed with the reagents and the emitted light...

  8. Pharmacological and molecular comparison of K(ATP) channels in rat basilar and middle cerebral arteries

    DEFF Research Database (Denmark)

    Ploug, Kenneth Beri; Edvinsson, Lars; Olesen, Jes

    2006-01-01

    , we studied the possible involvement of endothelial K(ATP) channels by pressurized arteriography after luminal administration of synthetic K(ATP) channel openers to rat basilar and middle cerebral arteries. Furthermore, we examined the mRNA and protein expression profile of K(ATP) channels to rat...... basilar and middle cerebral arteries using quantitative real-time PCR (Polymerase Chain Reaction) and Western blotting, respectively. In the perfusion system, we found no significant responses after luminal application of three K(ATP) channel openers to rat basilar and middle cerebral arteries...

  9. Extracellular ATP acts as a damage associated molecular pattern (DAMP signal in plants

    Directory of Open Access Journals (Sweden)

    Kiwamu eTanaka

    2014-09-01

    Full Text Available As sessile organisms, plants have evolved effective mechanisms to protect themselves from environmental stresses. Damaged (i.e., wounded plants recognize a variety of endogenous molecules as danger signals, referred to as damage-associated molecular patterns (DAMPs. ATP is among the molecules that are released by cell damage, and recent evidence suggests that ATP can serve as a DAMP. Although little studied in plants, extracellular ATP is well known for its signaling role in animals, including acting as a DAMP during the inflammatory response and wound healing. If ATP acts outside the cell, then it is reasonable to expect that it is recognized by a plasma membrane-localized receptor. Recently, DORN1, a lectin receptor kinase, was shown to recognize extracellular ATP in Arabidopsis. DORN1 is the founding member of a new purinoceptor subfamily, P2K (P2 receptor Kinase, which is plant-specific. P2K1 (DORN1 is required for ATP-induced cellular responses (e.g., cytosolic Ca2+ elevation, MAPK phosphorylation, and gene expression. Genetic analysis of loss-of-function mutants and overexpression lines showed that P2K1 participates in the plant wound response, consistent with the role of ATP as a DAMP. In this review, we summarize past research on the roles and mechanisms of extracellular ATP signaling in plants, and discuss the direction of the future research of extracellular ATP as a DAMP signal.

  10. Programming

    International Nuclear Information System (INIS)

    Jackson, M.A.

    1982-01-01

    The programmer's task is often taken to be the construction of algorithms, expressed in hierarchical structures of procedures: this view underlies the majority of traditional programming languages, such as Fortran. A different view is appropriate to a wide class of problem, perhaps including some problems in High Energy Physics. The programmer's task is regarded as having three main stages: first, an explicit model is constructed of the reality with which the program is concerned; second, this model is elaborated to produce the required program outputs; third, the resulting program is transformed to run efficiently in the execution environment. The first two stages deal in network structures of sequential processes; only the third is concerned with procedure hierarchies. (orig.)

  11. Programming

    OpenAIRE

    Jackson, M A

    1982-01-01

    The programmer's task is often taken to be the construction of algorithms, expressed in hierarchical structures of procedures: this view underlies the majority of traditional programming languages, such as Fortran. A different view is appropriate to a wide class of problem, perhaps including some problems in High Energy Physics. The programmer's task is regarded as having three main stages: first, an explicit model is constructed of the reality with which the program is concerned; second, thi...

  12. Program of scientific investigations and development of solid-oxide fuel cells (SOFC) in VNIITF. Proposals on scientific and technical collaboration and SOFC commercialization

    Energy Technology Data Exchange (ETDEWEB)

    Kleschev, Yu.N.; Chukharev, V.F.

    1996-04-01

    This paper describes proposals on scientific and technical collaborations pertaining to solid oxide fuel cell commercialization. Topics included for discussion are: materials research and manufacture; market estimation and cost; directions of collaboration; and project of proposals on joint enterprise creation.

  13. Splice Site Mutations in the ATP7A Gene

    DEFF Research Database (Denmark)

    Skjørringe, Tina; Tümer, Zeynep; Møller, Lisbeth Birk

    2011-01-01

    Menkes disease (MD) is caused by mutations in the ATP7A gene. We describe 33 novel splice site mutations detected in patients with MD or the milder phenotypic form, Occipital Horn Syndrome. We review these 33 mutations together with 28 previously published splice site mutations. We investigate 12...... mutations for their effect on the mRNA transcript in vivo. Transcriptional data from another 16 mutations were collected from the literature. The theoretical consequences of splice site mutations, predicted with the bioinformatics tool Human Splice Finder, were investigated and evaluated in relation...... to in vivo results. Ninety-six percent of the mutations identified in 45 patients with classical MD were predicted to have a significant effect on splicing, which concurs with the absence of any detectable wild-type transcript in all 19 patients investigated in vivo. Sixty-seven percent of the mutations...

  14. Mesurements of intracellular ATP provide new insight into the regulation of glycolysis in the yeast Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Ytting, Cecilie Karkov; Fuglsang, Anja Thoe; Hiltunen, J. Kalervo

    2012-01-01

    Glycolysis in the yeast Saccharomyces cerevisiae exhibits temporal oscillation under anaerobic or semianaerobic conditions. Previous evidence indicated that at least two membrane-bound ATPases, the mitochondrial F0F1 ATPase and the plasma membrane P-type ATPase (Pma1p), were important in regulating...... of the temporal behaviour of intracellular ATP in a yeast strain with oscillating glycolysis showed that, in addition to oscillation in intracellular ATP, there is an overall slow decrease in intracellular ATP because the ATP consumption rate exceeds the ATP production in glycolysis. Measurements of the temporal...... activity is under strict control. In the absence of glucose ATPase activity is switched off, and the intracellular ATP concentration is high. When glucose is added to the cells the ATP concentration starts to decrease, because ATP consumption exceeds ATP production by glycolysis. Finally, when glucose...

  15. Visualization and measurement of ATP levels in living cells replicating hepatitis C virus genome RNA.

    Directory of Open Access Journals (Sweden)

    Tomomi Ando

    Full Text Available Adenosine 5'-triphosphate (ATP is the primary energy currency of all living organisms and participates in a variety of cellular processes. Although ATP requirements during viral lifecycles have been examined in a number of studies, a method by which ATP production can be monitored in real-time, and by which ATP can be quantified in individual cells and subcellular compartments, is lacking, thereby hindering studies aimed at elucidating the precise mechanisms by which viral replication energized by ATP is controlled. In this study, we investigated the fluctuation and distribution of ATP in cells during RNA replication of the hepatitis C virus (HCV, a member of the Flaviviridae family. We demonstrated that cells involved in viral RNA replication actively consumed ATP, thereby reducing cytoplasmic ATP levels. Subsequently, a method to measure ATP levels at putative subcellular sites of HCV RNA replication in living cells was developed by introducing a recently-established Förster resonance energy transfer (FRET-based ATP indicator, called ATeam, into the NS5A coding region of the HCV replicon. Using this method, we were able to observe the formation of ATP-enriched dot-like structures, which co-localize with non-structural viral proteins, within the cytoplasm of HCV-replicating cells but not in non-replicating cells. The obtained FRET signals allowed us to estimate ATP concentrations within HCV replicating cells as ∼5 mM at possible replicating sites and ∼1 mM at peripheral sites that did not appear to be involved in HCV replication. In contrast, cytoplasmic ATP levels in non-replicating Huh-7 cells were estimated as ∼2 mM. To our knowledge, this is the first study to demonstrate changes in ATP concentration within cells during replication of the HCV genome and increased ATP levels at distinct sites within replicating cells. ATeam may be a powerful tool for the study of energy metabolism during replication of the viral genome.

  16. Tomatidine Is a Lead Antibiotic Molecule That Targets Staphylococcus aureus ATP Synthase Subunit C.

    Science.gov (United States)

    Lamontagne Boulet, Maxime; Isabelle, Charles; Guay, Isabelle; Brouillette, Eric; Langlois, Jean-Philippe; Jacques, Pierre-Étienne; Rodrigue, Sébastien; Brzezinski, Ryszard; Beauregard, Pascale B; Bouarab, Kamal; Boyapelly, Kumaraswamy; Boudreault, Pierre-Luc; Marsault, Éric; Malouin, François

    2018-06-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of deadly hospital-acquired infections. The discovery of anti- Staphylococcus antibiotics and new classes of drugs not susceptible to the mechanisms of resistance shared among bacteria is imperative. We recently showed that tomatidine (TO), a steroidal alkaloid from solanaceous plants, possesses potent antibacterial activity against S. aureus small-colony variants (SCVs), the notoriously persistent form of this bacterium that has been associated with recurrence of infections. Here, using genomic analysis of in vitro -generated TO-resistant S. aureus strains to identify mutations in genes involved in resistance, we identified the bacterial ATP synthase as the cellular target. Sequence alignments were performed to highlight the modified sequences, and the structural consequences of the mutations were evaluated in structural models. Overexpression of the atpE gene in S. aureus SCVs or introducing the mutation found in the atpE gene of one of the high-level TO-resistant S. aureus mutants into the Bacillus subtilis atpE gene provided resistance to TO and further validated the identity of the cellular target. FC04-100, a TO derivative which also possesses activity against non-SCV strains, prevents high-level resistance development in prototypic strains and limits the level of resistance observed in SCVs. An ATP synthesis assay allowed the observation of a correlation between antibiotic potency and ATP synthase inhibition. The selectivity index (inhibition of ATP production by mitochondria versus that of bacterial ATP synthase) is estimated to be >10 5 -fold for FC04-100. Copyright © 2018 American Society for Microbiology.

  17. The danger signal extracellular ATP is an inducer of Fusobacterium nucleatum biofilm dispersal

    Directory of Open Access Journals (Sweden)

    Qinfeng Ding

    2016-11-01

    Full Text Available Plaque biofilm is the primary etiological agent of periodontal disease. Biofilm formation progresses through multiple developmental stages beginning with bacterial attachment to a surface, followed by development of microcolonies and finally detachment and dispersal from a mature biofilm as free planktonic bacteria. Tissue damage arising from inflammatory response to biofilm is one of the hallmark features of periodontal disease. A consequence of tissue damage is the release of ATP from within the cell into the extracellular space. Extracellular ATP (eATP is an example of a danger associated molecular pattern (DAMP employed by mammalian cells to elicit inflammatory and damage healing responses. Although the roles of eATP as a signaling molecule in multi-cellular organisms have been relatively well studied, exogenous ATP also influences bacteria biofilm formation. Since plaque biofilms are continuously exposed to various stresses including exposure to the host damage factors eATP, we hypothesized that eATP, in addition to eliciting inflammation could potentially influence the biofilm lifecycle of periodontal associated bacteria. We found that eATP rather than nutritional factors or oxidative stress induced dispersal of Fusobacterium nucleatum, an organism associated with periodontal disease. eATP induced biofilm dispersal through chelating metal ions present in biofilm. Dispersed F. nucleatum biofilm, regardless of natural or induced dispersal by exogenous ATP, were significantly more adhesive and invasive compared to planktonic or biofilm counterparts, and correspondingly activated significantly more pro-inflammatory cytokine production in infected periodontal fibroblasts. Dispersed F. nucleatum also exhibited significantly higher expression of fadA, a virulence factor implicated in adhesion and invasion, compared to planktonic or biofilm bacteria. This study revealed for the first time that periodontal bacterium is capable of co-opting eATP, a

  18. Insulin induces a positive relationship between the rates of ATP and glycogen changes in isolated rat liver in presence of glucose; a 31P and 13C NMR study

    Directory of Open Access Journals (Sweden)

    Gin Henri

    2005-11-01

    Full Text Available Abstract Background There is an emerging theory suggesting that insulin, which is known to be the predominant postprandial anabolic hormone, is also a major regulator of mitochondrial oxidative phosphorylation in human skeletal muscle. However, little is known about its effects in the liver. Since there is a theoretical relationship between glycogen metabolism and energy status, a simultaneous and continuous investigation of hepatic ATP and glycogen content was performed in intact and isolated perfused liver by 31P and 13C nuclear magnetic resonance (NMR The hepatic rates of ATP and glycogen changes were evaluated with different concentrations of insulin and glucose during continuous and short-term supply. Results Liver from rats fed ad libitum were perfused with Krebs-Henseleit Buffer (KHB(controls or KHB containing 6 mM glucose, 30 mM glucose, insulin alone, insulin + 6 mM glucose, insulin + 30 mM glucose. In the control, glycogenolysis occurred at a rate of -0.53 ± 0.021 %·min-1 and ATP content decreased at a rate of -0.28 ± 0.029 %·min-1. In the absence of insulin, there was a close proportional relationship between the glycogen flux and the glucose concentration, whereas ATP rates never varied. With insulin + glucose, both glycogen and ATP rates were strongly related to the glucose concentration; the magnitude of net glycogen flux was linearly correlated to the magnitude of net ATP flux: fluxglycogen = 72.543(fluxATP + 172.08, R2 = 0.98. Conclusion Only the co-infusion of 30 mM glucose and insulin led to (i a net glycogen synthesis, (ii the maintenance of the hepatic ATP content, and a strong positive correlation between their net fluxes. This has never previously been reported. The specific effect of insulin on ATP change is likely related to a rapid stimulation of the hepatic mitochondrial oxidative phosphorylation. We propose that variations in the correlation between rates of ATP and glycogen changes could be a probe for insulin

  19. Insulin induces a positive relationship between the rates of ATP and glycogen changes in isolated rat liver in presence of glucose; a 31P and 13C NMR study.

    Science.gov (United States)

    Baillet-Blanco, Laurence; Beauvieux, Marie-Christine; Gin, Henri; Rigalleau, Vincent; Gallis, Jean-Louis

    2005-11-21

    There is an emerging theory suggesting that insulin, which is known to be the predominant postprandial anabolic hormone, is also a major regulator of mitochondrial oxidative phosphorylation in human skeletal muscle. However, little is known about its effects in the liver. Since there is a theoretical relationship between glycogen metabolism and energy status, a simultaneous and continuous investigation of hepatic ATP and glycogen content was performed in intact and isolated perfused liver by 31P and 13C nuclear magnetic resonance (NMR) The hepatic rates of ATP and glycogen changes were evaluated with different concentrations of insulin and glucose during continuous and short-term supply. Liver from rats fed ad libitum were perfused with Krebs-Henseleit Buffer (KHB)(controls) or KHB containing 6 mM glucose, 30 mM glucose, insulin alone, insulin + 6 mM glucose, insulin + 30 mM glucose. In the control, glycogenolysis occurred at a rate of -0.53 +/- 0.021 % x min(-1) and ATP content decreased at a rate of -0.28 +/- 0.029 % x min(-1). In the absence of insulin, there was a close proportional relationship between the glycogen flux and the glucose concentration, whereas ATP rates never varied. With insulin + glucose, both glycogen and ATP rates were strongly related to the glucose concentration; the magnitude of net glycogen flux was linearly correlated to the magnitude of net ATP flux: flux(glycogen) = 72.543(fluxATP) + 172.08, R2 = 0.98. Only the co-infusion of 30 mM glucose and insulin led to (i) a net glycogen synthesis, (ii) the maintenance of the hepatic ATP content, and a strong positive correlation between their net fluxes. This has never previously been reported. The specific effect of insulin on ATP change is likely related to a rapid stimulation of the hepatic mitochondrial oxidative phosphorylation. We propose that variations in the correlation between rates of ATP and glycogen changes could be a probe for insulin resistance due to the action of substrates

  20. MRP transporters as membrane machinery in the bradykinin-inducible export of ATP.

    Science.gov (United States)

    Zhao, Yumei; Migita, Keisuke; Sun, Jing; Katsuragi, Takeshi

    2010-04-01

    Adenosine triphosphate (ATP) plays the role of an autocrine/paracrine signal molecule in a variety of cells. So far, however, the membrane machinery in the export of intracellular ATP remains poorly understood. Activation of B2-receptor with bradykinin-induced massive release of ATP from cultured taenia coli smooth muscle cells. The evoked release of ATP was unaffected by gap junction hemichannel blockers, such as 18alpha-glycyrrhetinic acid and Gap 26. Furthermore, the cystic fibrosis transmembrane regulator (CFTR) coupled Cl(-) channel blockers, CFTR(inh)172, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, Gd3(+) and glibenclamide, failed to suppress the export of ATP by bradykinin. On the other, the evoked release of ATP was greatly reduced by multidrug resistance protein (MRP) transporter inhibitors, MK-571, indomethacin, and benzbromarone. From western blotting analysis, blots of MRP 1 protein only, but not MRP 2 and MRP 3 protein, appeared at 190 kD. However, the MRP 1 protein expression was not enhanced after loading with 1 muM bradykinin for 5 min. Likewise, niflumic acid and fulfenamic acid, Ca2(+)-activated Cl(-) channel blockers, largely abated the evoked release of ATP. The possibility that the MRP transporter system couples with Ca2(+)-activated Cl(-) channel activities is discussed here. These findings suggest that MRP transporters, probably MRP 1, unlike CFTR-Cl(-) channels and gap junction hemichannels, may contribute as membrane machinery to the export of ATP induced by G-protein-coupled receptor stimulation.