7 CFR 272.10 - ADP/CIS Model Plan.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false ADP/CIS Model Plan. 272.10 Section 272.10 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE... benefit computation (including but not limited to all household members' names, addresses, dates of birth...

7 CFR 277.18 - Establishment of an Automated Data Processing (ADP) and Information Retrieval System.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) and Information Retrieval System. 277.18 Section 277.18 Agriculture Regulations of the Department of... Data Processing (ADP) and Information Retrieval System. (a) Scope and application. This section... costs of planning, design, development or installation of ADP and information retrieval systems if the...

7 CFR 277.18 - Establishment of an Automated Data Processing (ADP) and Information Retrieval System.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) and Information Retrieval System. 277.18 Section 277.18 Agriculture Regulations of the Department of... Data Processing (ADP) and Information Retrieval System. (a) Scope and application. This section... costs of planning, design, development or installation of ADP and information retrieval systems if the...

7 CFR 277.18 - Establishment of an Automated Data Processing (ADP) and Information Retrieval System.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) and Information Retrieval System. 277.18 Section 277.18 Agriculture Regulations of the Department of... Data Processing (ADP) and Information Retrieval System. (a) Scope and application. This section... costs of planning, design, development or installation of ADP and information retrieval systems if the...

7 CFR 277.18 - Establishment of an Automated Data Processing (ADP) and Information Retrieval System.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) and Information Retrieval System. 277.18 Section 277.18 Agriculture Regulations of the Department of... Data Processing (ADP) and Information Retrieval System. (a) Scope and application. This section... costs of planning, design, development or installation of ADP and information retrieval systems if the...

Overview of Computer Security Certification and Accreditation. Final Report.

ERIC Educational Resources Information Center

Ruthberg, Zella G.; Neugent, William

Primarily intended to familiarize ADP (automatic data processing) policy and information resource managers with the approach to computer security certification and accreditation found in "Guideline to Computer Security Certification and Accreditation," Federal Information Processing Standards Publications (FIPS-PUB) 102, this overview…

Information Security Program Regulation

DTIC Science & Technology

1986-06-01

above. When an alarmed area is used for the storage of Top Secret material, the physical barrier must be adequate to prevent (a) surreptitious removal ...IV-9 4-304 Removable ADP and Word Processing Storage Media ---------- IV-10 4-305 Documents Produced by ADP Equipment...with a removal or cancellation of the classification designation. 1-315 Declassification Event An event that eliminates the need for continued

Defense ADP Acquisition Study.

DTIC Science & Technology

1981-11-30

Logistics ALS - Advanced Logistics System AMP - ADPS Master Plan ANSI - American National Standards Institute APR - Agency Procurement Request ASD(C...Computers IRM - Information Resources Management ISO - International Standards Organization L LCC - Life Cycle Costs LCM - Life Cycle Management LE...man- agement in the process * Lack of a mission orientation . Lack of systems management and life cycle perspectives * Lack of effective leadership

Mobilization and Defense Management Technical Reports Series. Acquisition of ADP (Automated Data Processing) by the Army during Mobilization.

DTIC Science & Technology

1983-03-01

have both a Federal and a State mission. The State mission is to provide protection of life and property and to preserve peace and public safety. The...logistics system is basically the same and will be integrated into the active system in wartime. Financial man- agement support consists of financial...the entire system is security. ErS is on contract to furnish basic security as well as a higher type of security known as the enhanced version

A Five-Year Plan for Meeting the Automatic Data Processing and Telecommunications Needs of the Federal Government. Volume l: Planning Strategies.

ERIC Educational Resources Information Center

Department of Commerce, Washington, DC.

The first of two volumes, this document describes the planning process of a 5-year plan for meeting the telecommunications and automatic data processing (ADP) needs of the federal government, examines the planning efforts of several typical agencies, and explores issues involved in managing new technology as it evolves. For each agency,…

NASA Crew Exploration Vehicle, Thermal Protection System, Lessons Learned

NASA Technical Reports Server (NTRS)

Venkatapathy, Ethiraj; Reuther, James

2008-01-01

The Orion (CEV) thermal protection system (TPS) advanced development project (ADP) was initiated in late 2006 to reduce developmental risk by significant investment in multiple heat shield architectural solutions that can meet the needs both the Low Earth orbit (LEO) and Lunar return missions. At the same time, the CEV TPS ADP was also charged with developing a preliminary design for the heat shield to meet the PDR requirement and at the time of the PDR, transfer the design to Lockheed- Martin, the prime contractor. We reported on the developmental activities of the first 18 months at the IPPW5 in Bordeaux, France, last summer. In June 08, at the time of the IPPW6, the CEV TPS ADP would have nearly completed the preparation for the Orion PDR and would be close to the original three-year mark. We plan to report on the progress at the Atlanta workshop. In the past year, Orion TPS ADP investment in TPS Technology, especially in PICA ablative Heat-shield design, development, testing and engineering (DDTE) has paid off in enabling MSL mission to switch from SLA 561 V heat shield to PICA heat shield. CEV TPS ADP considered SLA 561 V as a candidate for LEO missions and our testing identified failure modes in SLA and as a result, we dropped SLA for further evaluation. This close synergy between two projects is a highly visible example of how investment in technology areas can and does benefit multiple missions. In addition, CEV TPS ADP has been able to revive the Apollo ablative system namely AVCOAT honeycomb architecture as an alternate to the baseline PICA architecture and we plan to report the progress we have made in AVCOAT. CEV TPS ADP has invested considerable resources in developing analytical models for PICA and AVCOAT, material property measurements that is essential to the design of the heat-shield, in arcjet testing, in understanding the differences between different arc jet facilities, namely NASA Ames, NASA JSC and Air Force's AEDC, and in Non-Destructive Evaluation (NDE), and in integration of and manufacturing heat shield as a system. The capabilities of the two heat shield systems including failure modes via testing and analysis, once established, can serve the Probe Community and future mission designers to inner and outer planetary exploration very well. For example, missions to Venus, Mars and Titan can use either one of the system by selecting the mission design parameters that utilizes the full characteristics of these system to make use of system efficiency that will result in reduced heat shield mass, system robustness that will enhance mission success and cost. We plan to present significant progresses of the past three years and highlight the significant contributions CEV TPS ADP Project has made to advance the state of the art in Thermal Protection System technology that has and will continue to benefit future entry probe missions.

75 FR 5606 - Privacy Act of 1974; Report of an Altered System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Privacy Act...; and the DHHS Information Resources Management Manual, Part 6, ``ADP Systems Security.'' Retention and... Professions, Health Resources and Services Administration, Department of Health and Human Services, 5600...

ADP SYSTEMS ANALYSIS - COMMITTED VS. AVAILABLE MILITARY TRANSPORTATION (LMI T1).

DTIC Science & Technology

LOGISTICS , * MANAGEMENT ENGINEERING), (*DATA PROCESSING, LOGISTICS), INFORMATION RETRIEVAL, SYSTEMS ENGINEERING, MILITARY TRANSPORTATION, CARGO VEHICLES, SCHEDULING, COMPUTER PROGRAMMING, MANAGEMENT PLANNING AND CONTROL

Space Communications and Navigation (SCaN) Integrated Network Architecture Definition Document (ADD). Volume 1; Executive Summary; Revision 1

NASA Technical Reports Server (NTRS)

Younes, Badri A.; Schier, James S.

2010-01-01

The SCaN Program has defined an integrated network architecture that fully meets the Administrator s mandate to the Program, and will result in a NASA infrastructure capable of providing the needed and enabling communications services to future space missions. The integrated network architecture will increase SCaN operational efficiency and interoperability through standardization, commonality and technology infusion. It will enable NASA missions requiring advanced communication and tracking capabilities such as: a. Optical communication b. Antenna arraying c. Lunar and Mars Relays d. Integrated network management (service management and network control) and integrated service execution e. Enhanced tracking for navigation f. Space internetworking with DTN and IP g. End-to-end security h. Enhanced security services Moreover, the SCaN Program has created an Integrated Network Roadmap that depicts an orchestrated and coherent evolution path toward the target architecture, encompassing all aspects that concern network assets (i.e., operations and maintenance, sustaining engineering, upgrade efforts, and major development). This roadmap identifies major NASA ADPs, and shows dependencies and drivers among the various planned undertakings and timelines. The roadmap is scalable to accommodate timely adjustments in response to Agency needs, goals, objectives and funding. Future challenges to implementing this architecture include balancing user mission needs, technology development, and the availability of funding within NASA s priorities. Strategies for addressing these challenges are to: define a flexible architecture, update the architecture periodically, use ADPs to evaluate options and determine when to make decisions, and to engage the stakeholders in these evaluations. In addition, the SCaN Program will evaluate and respond to mission need dates for technical and operational capabilities to be provided by the SCaN integrated network. In that regard, the architecture defined in this ADD is scalable to accommodate programmatic and technical changes.

Thermal Protection System (Heat Shield) Development - Advanced Development Project

NASA Technical Reports Server (NTRS)

Kowal, T. John

2010-01-01

The Orion Thermal Protection System (TPS) ADP was a 3 1/2 year effort to develop ablative TPS materials for the Orion crew capsule. The ADP was motivated by the lack of available ablative TPS's. The TPS ADP pursued a competitive phased development strategy with succeeding rounds of development, testing and down selections. The Project raised the technology readiness level (TRL) of 8 different TPS materials from 5 different commercial vendors, eventual down selecting to a single material system for the Orion heat shield. In addition to providing a heat shield material and design for Orion on time and on budget, the Project accomplished the following: 1) Re-invigorated TPS industry & re-established a NASA competency to respond to future TPS needs; 2) Identified a potentially catastrophic problem with the planned MSL heat shield, and provided a viable, high TRL alternate heat shield design option; and 3) Transferred mature heat shield material and design options to the commercial space industry, including TPS technology information for the SpaceX Dragon capsule.

7 CFR 272.10 - ADP/CIS Model Plan.

Code of Federal Regulations, 2011 CFR

2011-01-01

... those which result in effective programs or in cost effective reductions in errors and improvements in management efficiency, such as decreases in program administrative costs. Thus, for those State agencies which operate exceptionally efficient and effective programs, a lesser degree of automation may be...

7 CFR 272.10 - ADP/CIS Model Plan.

Code of Federal Regulations, 2012 CFR

2012-01-01

... authorizations for benefits in issuance systems employing ATP's, direct mail, or online issuance and store all... and replacement; (2) FNS-250—Reconciliation of redeemed ATPs with reported authorized coupon issuance. (B) Reconciliation: FNS-46—ATP Reconciliation Report. (vii) Generate data necessary to meet other...

7 CFR 272.10 - ADP/CIS Model Plan.

Code of Federal Regulations, 2013 CFR

2013-01-01

... authorizations for benefits in issuance systems employing ATP's, direct mail, or online issuance and store all... and replacement; (2) FNS-250—Reconciliation of redeemed ATPs with reported authorized coupon issuance. (B) Reconciliation: FNS-46—ATP Reconciliation Report. (vii) Generate data necessary to meet other...

7 CFR 272.10 - ADP/CIS Model Plan.

Code of Federal Regulations, 2014 CFR

2014-01-01

... authorizations for benefits in issuance systems employing ATP's, direct mail, or online issuance and store all... and replacement; (2) FNS-250—Reconciliation of redeemed ATPs with reported authorized coupon issuance. (B) Reconciliation: FNS-46—ATP Reconciliation Report. (vii) Generate data necessary to meet other...

NASA Information Technology Implementation Plan

NASA Technical Reports Server (NTRS)

2000-01-01

NASA's Information Technology (IT) resources and IT support continue to be a growing and integral part of all NASA missions. Furthermore, the growing IT support requirements are becoming more complex and diverse. The following are a few examples of the growing complexity and diversity of NASA's IT environment. NASA is conducting basic IT research in the Intelligent Synthesis Environment (ISE) and Intelligent Systems (IS) Initiatives. IT security, infrastructure protection, and privacy of data are requiring more and more management attention and an increasing share of the NASA IT budget. Outsourcing of IT support is becoming a key element of NASA's IT strategy as exemplified by Outsourcing Desktop Initiative for NASA (ODIN) and the outsourcing of NASA Integrated Services Network (NISN) support. Finally, technology refresh is helping to provide improved support at lower cost. Recently the NASA Automated Data Processing (ADP) Consolidation Center (NACC) upgraded its bipolar technology computer systems with Complementary Metal Oxide Semiconductor (CMOS) technology systems. This NACC upgrade substantially reduced the hardware maintenance and software licensing costs, significantly increased system speed and capacity, and reduced customer processing costs by 11 percent.

Assessment of Techniques for Evaluating Computer Systems for Federal Agency Procurements. Final Report.

ERIC Educational Resources Information Center

Letmanyi, Helen

Developed to identify and qualitatively assess computer system evaluation techniques for use during acquisition of general purpose computer systems, this document presents several criteria for comparison and selection. An introduction discusses the automatic data processing (ADP) acquisition process and the need to plan for uncertainty through…

33 CFR 103.510 - Area Maritime Security (AMS) Plan review and approval.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Area Maritime Security (AMS) Plan... HOMELAND SECURITY MARITIME SECURITY MARITIME SECURITY: AREA MARITIME SECURITY Area Maritime Security (AMS) Plan § 103.510 Area Maritime Security (AMS) Plan review and approval. Each AMS Plan will be submitted...

49 CFR 659.23 - System security plan: contents.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false System security plan: contents. 659.23 Section 659... State Oversight Agency § 659.23 System security plan: contents. The system security plan must, at a... system security plan; and (e) Document the rail transit agency's process for making its system security...

Adenovirus Death Protein (ADP) Is Required for Lytic Infection of Human Lymphocytes

PubMed Central

Murali, V. K.; Ornelles, D. A.; Gooding, L. R.; Wilms, H. T.; Huang, W.; Tollefson, A. E.; Wold, W. S. M.

2014-01-01

The adenovirus death protein (ADP) is expressed at late times during a lytic infection of species C adenoviruses. ADP promotes the release of progeny virus by accelerating the lysis and death of the host cell. Since some human lymphocytes survive while maintaining a persistent infection with species C adenovirus, we compared ADP expression in these cells with ADP expression in lymphocytes that proceed with a lytic infection. Levels of ADP were low in KE37 and BJAB cells, which support a persistent infection. In contrast, levels of ADP mRNA and protein were higher in Jurkat cells, which proceed with a lytic infection. Epithelial cells infected with an ADP-overexpressing virus died more quickly than epithelial cells infected with an ADP-deleted virus. However, KE37, and BJAB cells remained viable after infection with the ADP-overexpressing virus. Although the levels of ADP mRNA increased in KE37 and BJAB cells infected with the ADP-overexpressing virus, the fraction of cells with detectable ADP was unchanged, suggesting that the control of ADP expression differs between epithelial and lymphocytic cells. When infected with an ADP-deleted adenovirus, Jurkat cells survived and maintained viral DNA for greater than 1 month. These findings are consistent with the notion that the level of ADP expression determines whether lymphocytic cells proceed with a lytic or a persistent adenovirus infection. PMID:24198418

Engaging Educators: Common Core State Standards Implementation

ERIC Educational Resources Information Center

Achieve, Inc., 2011

2011-01-01

To date, 44 states and the District of Columbia have adopted the Common Core State Standards (CCSS). Achieve has prepared this planning document to help all states in the American Diploma Project Network (ADP) and the Partnership for Assessment of Readiness for College and Careers (PARCC) consortium engage educators in the essential work of…

6 CFR 37.41 - Security plan.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Security plan. 37.41 Section 37.41 Domestic... Security plan. (a) In General. States must have a security plan that addresses the provisions in paragraph (b) of this section and must submit the security plan as part of its REAL ID certification under § 37...

The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylation

PubMed Central

Mueller-Dieckmann, Christoph; Kernstock, Stefan; Lisurek, Michael; von Kries, Jens Peter; Haag, Friedrich; Weiss, Manfred S.; Koch-Nolte, Friedrich

2006-01-01

Posttranslational modifications are used by cells from all kingdoms of life to control enzymatic activity and to regulate protein function. For many cellular processes, including DNA repair, spindle function, and apoptosis, reversible mono- and polyADP-ribosylation constitutes a very important regulatory mechanism. Moreover, many pathogenic bacteria secrete toxins which ADP-ribosylate human proteins, causing diseases such as whooping cough, cholera, and diphtheria. Whereas the 3D structures of numerous ADP-ribosylating toxins and related mammalian enzymes have been elucidated, virtually nothing is known about the structure of protein de-ADP-ribosylating enzymes. Here, we report the 3Dstructure of human ADP-ribosylhydrolase 3 (hARH3). The molecular architecture of hARH3 constitutes the archetype of an all-α-helical protein fold and provides insights into the reversibility of protein ADP-ribosylation. Two magnesium ions flanked by highly conserved amino acids pinpoint the active-site crevice. Recombinant hARH3 binds free ADP-ribose with micromolar affinity and efficiently de-ADP-ribosylates poly- but not monoADP-ribosylated proteins. Docking experiments indicate a possible binding mode for ADP-ribose polymers and suggest a reaction mechanism. Our results underscore the importance of endogenous ADP-ribosylation cycles and provide a basis for structure-based design of ADP-ribosylhydrolase inhibitors. PMID:17015823

Characterization of the catalytic and noncatalytic ADP binding sites of the F1-ATPase from the thermophilic bacterium, PS3

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

Yoshida, M.; Allison, W.S.

1986-05-05

Two classes of ADP binding sites at 20 degrees C have been characterized in the F1-ATPase from the thermophilic bacterium, PS3 (TF1). One class is comprised of three sites which saturate with (/sup 3/H)ADP in less than 10 s with a Kd of 10 microM which, once filled, exchange rapidly with medium ADP. The binding of ADP to these sites is dependent on Mg2+. (/sup 3/H)ADP bound to these sites is removed by repeated gel filtrations on centrifuge columns equilibrated with ADP free medium. The other class is comprised of a single site which saturates with (/sup 3/H)ADP in 30more » min with a Kd of 30 microM. (/sup 3/H)ADP bound to this site does not exchange with medium ADP nor does it dissociate on gel filtration through centrifuge columns equilibrated with ADP free medium. Binding of (/sup 3/H)ADP to this site is weaker in the presence of Mg2+ where the Kd for ADP is about 100 microM. (/sup 3/H)ADP dissociated from this site when ATP plus Mg2+ was added to the complex while it remained bound in the presence of ATP alone or in the presence of ADP, Pi, or ADP plus Pi with or without added Mg2+. Significant amounts of ADP in the 1:1 TF1.ADP complex were converted to ATP in the presence of Pi, Mg2+, and 50% dimethyl sulfoxide. Enzyme-bound ATP synthesis was abolished by chemical modification of a specific glutamic acid residue by dicyclohexylcarbodiimide, but not by modification of a specific tyrosine residue with 7-chloro-4-nitrobenzofurazan. Difference circular dichroism spectra revealed that the three Mg2+ -dependent, high affinity ADP binding sites that were not stable to gel filtration were on the alpha subunits and that the single ADP binding site that was stable to gel filtration was on one of the three beta subunits.« less

ADP-ribosyl-N₃: A Versatile Precursor for Divergent Syntheses of ADP-ribosylated Compounds.

PubMed

Li, Lingjun; Li, Qianqian; Ding, Shengqiang; Xin, Pengyang; Zhang, Yuqin; Huang, Shenlong; Zhang, Guisheng

2017-08-14

Adenosine diphosphate-ribose (ADP-ribose) and its derivatives play important roles in a series of complex physiological procedures. The design and synthesis of artificial ADP-ribosylated compounds is an efficient way to develop valuable chemical biology tools and discover new drug candidates. However, the synthesis of ADP-ribosylated compounds is currently difficult due to structural complexity, easily broken pyrophosphate bond and high hydrophilicity. In this paper, ADP-ribosyl-N₃ was designed and synthesized for the first time. With ADP-ribosyl-N₃ as the key precursor, a divergent post-modification strategy was developed to prepare structurally diverse ADP-ribosylated compounds including novel nucleotides and peptides bearing ADP-ribosyl moieties.

49 CFR 172.802 - Components of a security plan.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Components of a security plan. 172.802 Section 172... TABLE, SPECIAL PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY RESPONSE INFORMATION, TRAINING REQUIREMENTS, AND SECURITY PLANS Safety and Security Plans § 172.802 Components of a security plan. (a) The...

49 CFR 172.802 - Components of a security plan.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Components of a security plan. 172.802 Section 172... TABLE, SPECIAL PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY RESPONSE INFORMATION, TRAINING REQUIREMENTS, AND SECURITY PLANS Safety and Security Plans § 172.802 Components of a security plan. (a) The...

49 CFR 172.802 - Components of a security plan.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Components of a security plan. 172.802 Section 172... TABLE, SPECIAL PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY RESPONSE INFORMATION, TRAINING REQUIREMENTS, AND SECURITY PLANS Safety and Security Plans § 172.802 Components of a security plan. (a) The...

49 CFR 172.802 - Components of a security plan.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Components of a security plan. 172.802 Section 172... TABLE, SPECIAL PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY RESPONSE INFORMATION, TRAINING REQUIREMENTS, AND SECURITY PLANS Safety and Security Plans § 172.802 Components of a security plan. (a) The...

Identification of a receptor for ADP on blood platelets by photoaffinity labelling.

PubMed Central

Cristalli, G; Mills, D C

1993-01-01

The synthesis of a new analogue of ADP, 2-(p-azidophenyl)-ethythioadenosine 5'-diphosphate (AzPET-ADP), is described. This compound contains a photolabile phenylazide group attached to the ADP molecule by a thioether link at the purine 2 position. It has been prepared in radioactive form with 32P in the beta-phosphate at a specific radioactivity of 100 mCi/mumol. The reagent activated platelets, causing shape change and aggregation, with somewhat lower affinity than ADP. On photolysis the affinity was increased. The reagent also inhibited platelet adenylate cyclase stimulation by prostaglandin E1, with considerably higher affinity than ADP. On photolysis the affinity was decreased. AzPET-ADP competitively inhibited the binding of 2-methylthio[beta-32P]ADP, a ligand for the receptor by which ADP causes inhibition of adenylate cyclase. In the dark, AzPET-[beta-32P]ADP bound reversibly and with high affinity to a single population of sites similar in number to the sites that bind 2-methylthio[beta-32P]ADP. Binding was inhibited by ADP and by ATP and by p-chloromercuribenzenesulphonic acid (pCMBS). On exposure to u.v. light in the presence of platelets, AzPET-[beta-32P]ADP was incorporated covalently but non-specifically into several platelet proteins, although prominent intracellular proteins were not labelled. Specific labelling was confined to a single region of SDS/polyacrylamide gels, overlying but not comigrating with actin. Incorporation of radioactivity into this region was inhibited by ADP and by ATP as well as by ADP beta S, ATP alpha S and pCMBS, but not by adenosine, GDP or AMP. Inhibition of AzPET-[beta-32P]ADP incorporation was closely correlated with inhibition of equilibrium binding of 2-methylthio[beta-32P]ADP. These results suggests that the labelled protein, which migrates with an apparent molecular mass of 43 kDa in reduced gels, is the receptor through which ADP inhibits adenylate cyclase. Images Figure 5 PMID:8387782

Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?

PubMed Central

Hassa, Paul O.; Haenni, Sandra S.; Elser, Michael; Hottiger, Michael O.

2006-01-01

Since poly-ADP ribose was discovered over 40 years ago, there has been significant progress in research into the biology of mono- and poly-ADP-ribosylation reactions. During the last decade, it became clear that ADP-ribosylation reactions play important roles in a wide range of physiological and pathophysiological processes, including inter- and intracellular signaling, transcriptional regulation, DNA repair pathways and maintenance of genomic stability, telomere dynamics, cell differentiation and proliferation, and necrosis and apoptosis. ADP-ribosylation reactions are phylogenetically ancient and can be classified into four major groups: mono-ADP-ribosylation, poly-ADP-ribosylation, ADP-ribose cyclization, and formation of O-acetyl-ADP-ribose. In the human genome, more than 30 different genes coding for enzymes associated with distinct ADP-ribosylation activities have been identified. This review highlights the recent advances in the rapidly growing field of nuclear mono-ADP-ribosylation and poly-ADP-ribosylation reactions and the distinct ADP-ribosylating enzyme families involved in these processes, including the proposed family of novel poly-ADP-ribose polymerase-like mono-ADP-ribose transferases and the potential mono-ADP-ribosylation activities of the sirtuin family of NAD+-dependent histone deacetylases. A special focus is placed on the known roles of distinct mono- and poly-ADP-ribosylation reactions in physiological processes, such as mitosis, cellular differentiation and proliferation, telomere dynamics, and aging, as well as “programmed necrosis” (i.e., high-mobility-group protein B1 release) and apoptosis (i.e., apoptosis-inducing factor shuttling). The proposed molecular mechanisms involved in these processes, such as signaling, chromatin modification (i.e., “histone code”), and remodeling of chromatin structure (i.e., DNA damage response, transcriptional regulation, and insulator function), are described. A potential cross talk between nuclear ADP-ribosylation processes and other NAD+-dependent pathways is discussed. PMID:16959969

Toward a unified nomenclature for mammalian ADP-ribosyltransferases.

PubMed

Hottiger, Michael O; Hassa, Paul O; Lüscher, Bernhard; Schüler, Herwig; Koch-Nolte, Friedrich

2010-04-01

ADP-ribosylation is a post-translational modification of proteins catalyzed by ADP-ribosyltransferases. It comprises the transfer of the ADP-ribose moiety from NAD+ to specific amino acid residues on substrate proteins or to ADP-ribose itself. Currently, 22 human genes encoding proteins that possess an ADP-ribosyltransferase catalytic domain are known. Recent structural and enzymological evidence of poly(ADP-ribose)polymerase (PARP) family members demonstrate that earlier proposed names and classifications of these proteins are no longer accurate. Here we summarize these new findings and propose a new consensus nomenclature for all ADP-ribosyltransferases (ARTs) based on the catalyzed reaction and on structural features. A unified nomenclature would facilitate communication between researchers both inside and outside the ADP-ribosylation field. 2009 Elsevier Ltd. All rights reserved.

33 CFR 103.500 - General.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MARITIME SECURITY MARITIME SECURITY: AREA MARITIME SECURITY Area Maritime Security (AMS) Plan § 103.500 General. (a) The Area Maritime... with the National Maritime Transportation Security Plan and the National Transportation Security Plan...

7 CFR 277.18 - Establishment of an Automated Data Processing (ADP) and Information Retrieval System.

Code of Federal Regulations, 2010 CFR

2010-01-01

... activities and expenditures in relation to the approved Planning APD or Implementation APD. An APDU may also... organizations other than the State agency to perform such tasks as feasibility studies, system studies, system... requirements of § 277.18(c). Feasibility Study means a preliminary study to determine whether it is...

Photosynthetic antenna-reaction center mimicry with a covalently linked monostyryl boron-dipyrromethene-aza-boron-dipyrromethene-C60 triad.

PubMed

Shi, Wen-Jing; El-Khouly, Mohamed E; Ohkubo, Kei; Fukuzumi, Shunichi; Ng, Dennis K P

2013-08-19

An efficient functional mimic of the photosynthetic antenna-reaction center has been designed and synthesized. The model contains a near-infrared-absorbing aza-boron-dipyrromethene (ADP) that is connected to a monostyryl boron-dipyrromethene (BDP) by a click reaction and to a fullerene (C60 ) using the Prato reaction. The intramolecular photoinduced energy and electron-transfer processes of this triad as well as the corresponding dyads BDP-ADP and ADP-C60 have been studied with steady-state and time-resolved absorption and fluorescence spectroscopic methods in benzonitrile. Upon excitation, the BDP moiety of the triad is significantly quenched due to energy transfer to the ADP core, which subsequently transfers an electron to the fullerene unit. Cyclic and differential pulse voltammetric studies have revealed the redox states of the components, which allow estimation of the energies of the charge-separated states. Such calculations show that electron transfer from the singlet excited ADP ((1) ADP*) to C60 yielding ADP(.+) -C60 (.-) is energetically favorable. By using femtosecond laser flash photolysis, concrete evidence has been obtained for the occurrence of energy transfer from (1) BDP* to ADP in the dyad BDP-ADP and electron transfer from (1) ADP* to C60 in the dyad ADP-C60 . Sequential energy and electron transfer have also been clearly observed in the triad BDP-ADP-C60 . By monitoring the rise of ADP emission, it has been found that the rate of energy transfer is fast (≈10(11)  s(-1) ). The dynamics of electron transfer through (1) ADP* has also been studied by monitoring the formation of C60 radical anion at 1000 nm. A fast charge-separation process from (1) ADP* to C60 has been detected, which gives the relatively long-lived BDP-ADP(.+) C60 (.-) with a lifetime of 1.47 ns. As shown by nanosecond transient absorption measurements, the charge-separated state decays slowly to populate mainly the triplet state of ADP before returning to the ground state. These findings show that the dyads BDP-ADP and ADP-C60 , and the triad BDP-ADP-C60 are interesting artificial analogues that can mimic the antenna and reaction center of the natural photosynthetic systems. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

10 CFR 52.79 - Contents of applications; technical information in final safety analysis report.

Code of Federal Regulations, 2012 CFR

2012-01-01

... B to 10 CFR part 73. (iii) A cyber security plan in accordance with the criteria set forth in § 73..., training and qualification plan, and cyber security plan; and (v) Each applicant who prepares a physical security plan, a safeguards contingency plan, a training and qualification plan, or a cyber security plan...

10 CFR 52.79 - Contents of applications; technical information in final safety analysis report.

Code of Federal Regulations, 2013 CFR

2013-01-01

... B to 10 CFR part 73. (iii) A cyber security plan in accordance with the criteria set forth in § 73..., training and qualification plan, and cyber security plan; and (v) Each applicant who prepares a physical security plan, a safeguards contingency plan, a training and qualification plan, or a cyber security plan...

10 CFR 52.79 - Contents of applications; technical information in final safety analysis report.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) A cyber security plan in accordance with the criteria set forth in § 73.54 of this chapter; (iv) A... cyber security plan; and (v) Each applicant who prepares a physical security plan, a safeguards contingency plan, a training and qualification plan, or a cyber security plan, shall protect the plans and...

10 CFR 52.79 - Contents of applications; technical information in final safety analysis report.

Code of Federal Regulations, 2014 CFR

2014-01-01

... B to 10 CFR part 73. (iii) A cyber security plan in accordance with the criteria set forth in § 73..., training and qualification plan, and cyber security plan; and (v) Each applicant who prepares a physical security plan, a safeguards contingency plan, a training and qualification plan, or a cyber security plan...

Effect of an ADP analog on isometric force and ATPase activity of active muscle fibers.

PubMed

Karatzaferi, Christina; Myburgh, Kathryn H; Chinn, Marc K; Franks-Skiba, Kathleen; Cooke, Roger

2003-04-01

The role played by ADP in modulating cross-bridge function has been difficult to study, because it is hard to buffer ADP concentration in skinned muscle preparations. To solve this, we used an analog of ADP, spin-labeled ADP (SL-ADP). SL-ADP binds tightly to myosin but is a very poor substrate for creatine kinase or pyruvate kinase. Thus ATP can be regenerated, allowing well-defined concentrations of both ATP and SL-ADP. We measured isometric ATPase rate and isometric tension as a function of both [SL-ADP], 0.1-2 mM, and [ATP], 0.05-0.5 mM, in skinned rabbit psoas muscle, simulating fresh or fatigued states. Saturating levels of SL-ADP increased isometric tension (by P'), the absolute value of P' being nearly constant, approximately 0.04 N/mm(2), in variable ATP levels, pH 7. Tension decreased (50-60%) at pH 6, but upon addition of SL-ADP, P' was still approximately 0.04 N/mm(2). The ATPase was inhibited competitively by SL-ADP with an inhibition constant, K(i), of approximately 240 and 280 microM at pH 7 and 6, respectively. Isometric force and ATPase activity could both be fit by a simple model of cross-bridge kinetics.

Vault-poly-ADP-ribose polymerase in the Octopus vulgaris brain: a regulatory factor of actin polymerization dynamic.

PubMed

De Maio, Anna; Natale, Emiliana; Rotondo, Sergio; Di Cosmo, Anna; Faraone-Mennella, Maria Rosaria

2013-09-01

Our previous behavioural, biochemical and immunohistochemical analyses conducted in selected regions (supra/sub oesophageal masses) of the Octopus vulgaris brain detected a cytoplasmic poly-ADP-ribose polymerase (more than 90% of total enzyme activity). The protein was identified as the vault-free form of vault-poly-ADP-ribose polymerase. The present research extends and integrates the biochemical characterization of poly-ADP-ribosylation system, namely, reaction product, i.e., poly-ADP-ribose, and acceptor proteins, in the O. vulgaris brain. Immunochemical analyses evidenced that the sole poly-ADP-ribose acceptor was the octopus cytoskeleton 50-kDa actin. It was present in both free, endogenously poly-ADP-ribosylated form (70kDa) and in complex with V-poly-ADP-ribose polymerase and poly-ADP-ribose (260kDa). The components of this complex, alkali and high salt sensitive, were purified and characterized. The kind and the length of poly-ADP-ribose corresponded to linear chains of 30-35 ADP-ribose units, in accordance with the features of the polymer synthesized by the known vault-poly-ADP-ribose polymerase. In vitro experiments showed that V-poly-ADP-ribose polymerase activity of brain cytoplasmic fraction containing endogenous actin increased upon the addition of commercial actin and was highly reduced by ATP. Anti-actin immunoblot of the mixture in the presence and absence of ATP showed that the poly-ADP-ribosylation of octopus actin is a dynamic process balanced by the ATP-dependent polymerization of the cytoskeleton protein, a fundamental mechanism for synaptic plasticity. © 2013 Elsevier Inc. All rights reserved.

49 CFR 659.25 - Annual review of system safety program plan and system security plan.

Code of Federal Regulations, 2010 CFR

2010-10-01

... system security plan. 659.25 Section 659.25 Transportation Other Regulations Relating to Transportation... and system security plan. (a) The oversight agency shall require the rail transit agency to conduct an annual review of its system safety program plan and system security plan. (b) In the event the rail...

Release abilities of adenosine diphosphate from phospholipid vesicles with different membrane properties and their hemostatic effects as a platelet substitute.

PubMed

Okamura, Yosuke; Katsuno, Shunsuke; Suzuki, Hidenori; Maruyama, Hitomi; Handa, Makoto; Ikeda, Yasuo; Takeoka, Shinji

2010-12-20

We have constructed phospholipid vesicles with hemostatic activity as a platelet substitute. The vesicles were conjugated with a dodecapeptide (HHLGGAKQAGDV, H12), which is a fibrinogen γ-chain carboxy-terminal sequence (γ400-411). We have recently exploited these vesicles as a potential drug delivery system by encapsulation of adenosine 5'-diphosphate (ADP) (H12-(ADP)-vesicles). Here we explore the relationship between the ADP release from H12-(ADP)-vesicles with different membrane properties and their hemostatic effects. In total, we prepared five kinds of H12-(ADP)-vesicles with different lamellarities and membrane flexibilities. By radioisotope-labeling, we directly show that H12-(ADP)-vesicles were capable of augmenting platelet aggregation by releasing ADP in an aggregation-dependent manner. The amount of ADP released from the vesicles was dependent on their membrane properties. Specifically, the amount of ADP released increased with decreasing lamellarity and tended to increase with increasing membrane flexibility. Our in vivo results clearly demonstrated that H12-(ADP)-vesicles with the ability to release ADP exert considerable hemostatic action in terms of correcting prolonged bleeding time in a busulphan-induced thrombocytopenic rat model. We propose a recipe to control the hemostatic abilities of H12-(ADP)-vesicles by modulating ADP release based on membrane properties. We believe that this concept will be invaluable to the development of platelet substitutes and other drug carriers. Copyright © 2010 Elsevier B.V. All rights reserved.

Structural and computational analysis of peptide recognition mechanism of class-C type penicillin binding protein, alkaline D-peptidase from Bacillus cereus DF4-B

PubMed Central

Nakano, Shogo; Okazaki, Seiji; Ishitsubo, Erika; Kawahara, Nobuhiro; Komeda, Hidenobu; Tokiwa, Hiroaki; Asano, Yasuhisa

2015-01-01

Alkaline D-peptidase from Bacillus cereus DF4-B, called ADP, is a D-stereospecific endopeptidase reacting with oligopeptides containing D-phenylalanine (D-Phe) at N-terminal penultimate residue. ADP has attracted increasing attention because it is useful as a catalyst for synthesis of D-Phe oligopeptides or, with the help of substrate mimetics, L-amino acid peptides and proteins. Structure and functional analysis of ADP is expected to elucidate molecular mechanism of ADP. In this study, the crystal structure of ADP (apo) form was determined at 2.1 Å resolution. The fold of ADP is similar to that of the class C penicillin-binding proteins of type-AmpH. Docking simulations and fragment molecular orbital analyses of two peptides, (D-Phe)4 and (D-Phe)2-(L-Phe)2, with the putative substrate binding sites of ADP indicated that the P1 residue of the peptide interacts with hydrophobic residues at the S1 site of ADP. Furthermore, molecular dynamics simulation of ADP for 50 nsec suggested that the ADP forms large cavity at the active site. Formation of the cavity suggested that the ADP has open state in the solution. For the ADP, having the open state is convenient to bind the peptides having bulky side chain, such as (D-Phe)4. Taken together, we predicted peptide recognition mechanism of ADP. PMID:26370172

Effects of Site-Directed Mutagenesis of Escherichia coli Heat-Labile Enterotoxin on ADP-Ribosyltransferase Activity and Interaction with ADP-Ribosylation Factors

PubMed Central

A. Stevens, Linda; Moss, Joel; Vaughan, Martha; Pizza, Mariagrazia; Rappuoli, Rino

1999-01-01

Escherichia coli heat-labile enterotoxin (LT), an oligomeric protein with one A subunit (LTA) and five B subunits, exerts its effects via the ADP-ribosylation of Gsα, a guanine nucleotide-binding (G) protein that activates adenylyl cyclase. LTA also ADP-ribosylates simple guanidino compounds (e.g., arginine) and catalyzes its own auto-ADP-ribosylation. All LTA-catalyzed reactions are enhanced by ADP-ribosylation factors (ARFs), 20-kDa guanine nucleotide-binding proteins. Replacement of arginine-7 (R7K), valine-53 (V53D), serine-63 (S63K), valine 97 (V97K), or tyrosine-104 (Y104K) in LTA resulted in fully assembled but nontoxic proteins. S63K, V53D, and R7K are catalytic-site mutations, whereas V97K and Y104K are amino acid replacements adjacent to and outside of the catalytic site, respectively. The effects of mutagenesis were quantified by measuring ADP-ribosyltransferase activity (i.e., auto-ADP-ribosylation and ADP-ribosylagmatine synthesis) and interaction with ARF (i.e., inhibition of ARF-stimulated cholera toxin ADP-ribosyltransferase activity and effects of ARF on mutant auto-ADP-ribosylation). All mutants were inactive in the ADP-ribosyltransferase assay; however, auto-ADP-ribosylation in the presence of recombinant human ARF6 was detected, albeit much less than that of native LT (Y104K > V53D > V97K > R7K, S63K). Based on the lack of inhibition by free ADP-ribose, the observed auto-ADP-ribosylation activity was enzymatic and not due to the nonenzymatic addition of free ADP-ribose. V53D, S63K, and R7K were more effective than Y104K or V97K in blocking ARF stimulation of cholera toxin ADP-ribosyltransferase. Based on these data, it appears that ARF-binding and catalytic sites are not identical and that a region outside the NAD cleft may participate in the LTA-ARF interaction. PMID:9864224

The ARTT motif and a unified structural understanding of substraterecognition in ADP ribosylating bacterial toxins and eukaryotic ADPribosyltransferases

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

Han, S.; Tainer, J.A.

2001-08-01

ADP-ribosylation is a widely occurring and biologically critical covalent chemical modification process in pathogenic mechanisms, intracellular signaling systems, DNA repair, and cell division. The reaction is catalyzed by ADP-ribosyltransferases, which transfer the ADP-ribose moiety of NAD to a target protein with nicotinamide release. A family of bacterial toxins and eukaryotic enzymes has been termed the mono-ADP-ribosyltransferases, in distinction to the poly-ADP-ribosyltransferases, which catalyze the addition of multiple ADP-ribose groups to the carboxyl terminus of eukaryotic nucleoproteins. Despite the limited primary sequence homology among the different ADP-ribosyltransferases, a central cleft bearing NAD-binding pocket formed by the two perpendicular b-sheet core hasmore » been remarkably conserved between bacterial toxins and eukaryotic mono- and poly-ADP-ribosyltransferases. The majority of bacterial toxins and eukaryotic mono-ADP-ribosyltransferases are characterized by conserved His and catalytic Glu residues. In contrast, Diphtheria toxin, Pseudomonas exotoxin A, and eukaryotic poly-ADP-ribosyltransferases are characterized by conserved Arg and catalytic Glu residues. The NAD-binding core of a binary toxin and a C3-like toxin family identified an ARTT motif (ADP-ribosylating turn-turn motif) that is implicated in substrate specificity and recognition by structural and mutagenic studies. Here we apply structure-based sequence alignment and comparative structural analyses of all known structures of ADP-ribosyltransfeases to suggest that this ARTT motif is functionally important in many ADP-ribosylating enzymes that bear a NAD binding cleft as characterized by conserved Arg and catalytic Glu residues. Overall, structure-based sequence analysis reveals common core structures and conserved active sites of ADP-ribosyltransferases to support similar NAD binding mechanisms but differing mechanisms of target protein binding via sequence variations within the ARTT motif structural framework. Thus, we propose here that the ARTT motif represents an experimentally testable general recognition motif region for many ADP-ribosyltransferases and thereby potentially provides a unified structural understanding of substrate recognition in ADP-ribosylation processes.« less

Photoaffinity labeling of the TF1-ATPase from the thermophilic bacterium PS3 with 3'-O-(4-benzoyl)benzoyl ADP.

PubMed

Bar-Zvi, D; Yoshida, M; Shavit, N

1985-05-31

3'-O-(4-Benzoyl)benzoyl ADP (BzADP) was used as a photoaffinity label for covalent binding of adenine nucleotide analogs to the nucleotide binding site(s) of the thermophilic bacterium PS3 ATPase (TF1). As with the CF1-ATPase (Bar-Zvi, D. and Shavit, N. (1984) Biochim. Biophys. Acta 765, 340-356) noncovalently bound BzADP is a reversible inhibitor of the TF1-ATPase. BzADP changes the kinetics of ATP hydrolysis from noncooperative to cooperative in the same way as ADP does, but, in contrast to the effect on the CF1-ATPase, it has no effect on the Vmax. In the absence of Mg2+ 1 mol BzADP binds noncovalently to TF1, while with Mg2+ 3 mol are bound. Photoactivation of BzADP results in the covalent binding of the analog to the nucleotide binding site(s) on TF1 and correlates with the inactivation of the ATPase. Complete inactivation of the TF1-ATPase occurs after covalent binding of 2 mol BzADP/mol TF1. Photoinactivation of TF1 by BzADP is prevented if excess of either ADP or ATP is present during irradiation. Analysis by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate of the Bz[3H]ADP-labeled TF1-ATPase shows that all the radioactivity is incorporated into the beta subunit.

Pharmacokinetic study of the structural components of adenosine diphosphate-encapsulated liposomes coated with fibrinogen γ-chain dodecapeptide as a synthetic platelet substitute.

PubMed

Taguchi, Kazuaki; Ujihira, Hayato; Ogaki, Shigeru; Watanabe, Hiroshi; Fujiyama, Atsushi; Doi, Mami; Okamura, Yosuke; Takeoka, Shinji; Ikeda, Yasuo; Handa, Makoto; Otagiri, Masaki; Maruyama, Toru

2013-08-01

Fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV, H12)-coated, ADP-encapsulated liposomes [H12-(ADP)-liposomes] were developed as a synthetic platelet alternative that specifically accumulates at bleeding sites as the result of interactions with activated platelets via glycoprotein IIb/IIIa and augments platelet aggregation by releasing ADP. The aim of this study is to characterize the pharmacokinetic properties of H12-(ADP)-liposomes and structural components in rats, and to predict the blood retention of H12-(ADP)-liposomes in humans. With use of H12-(ADP)-liposomes in which the encapsulated ADP and liposomal membrane cholesterol were radiolabeled with (14)C and (3)H, respectively, it was found that the time courses for the plasma concentration curves of (14)C and (3)H radioactivity showed that the H12-(ADP)-liposomes remained intact in the blood circulation for up to 24 hours after injection, and were mainly distributed to the liver and spleen. However, the (14)C and (3)H radioactivity of H12-(ADP)-liposomes disappeared from organs within 7 days after injection. The encapsulated ADP was metabolized to allantoin, which is the final metabolite of ADP in rodents, and was mainly eliminated in the urine, whereas the cholesterol was mainly eliminated in feces. In addition, the half-life of the H12-(ADP)-liposomes in humans was predicted to be approximately 96 hours from pharmacokinetic data obtained for mice, rats, and rabbits using an allometric equation. These results suggest that the H12-(ADP)-liposome has potential with proper pharmacokinetic and acceptable biodegradable properties as a synthetic platelet substitute.

Asymmetry of the three catalytic sites on beta subunits of TF1 from a thermophilic Bacillus strain PS3.

PubMed

Hisabori, T; Kobayashi, H; Kaibara, C; Yoshida, M

1994-03-01

F1-ATPase isolated from plasma membrane of a thermophilic Bacillus strain PS3 (TF1) has very little or no endogenously bound adenine nucleotides. However, it can bind one ADP per mol of the enzyme on one of three beta subunits to form a stable TF1.ADP complex when incubated with a high concentration of ADP [Yoshida, M. & Allison, W.S. (1986) J. Biol. Chem. 261, 5714-5721]. The same TF1.ADP complex was recovered after filling all ADP binding sites with [3H]ADP and repeated gel filtration. Direct binding assay revealed that the TF1.ADP complex had lost the highest affinity site for TNP-ADP. When a substoichiometric amount of TNP-ATP was added, the complex hydrolyzed TNP-ATP slowly (single site hydrolysis), like native TF1. However, this hydrolysis was not promoted by chase-addition of excess ATP. The optimal pH of the ATPase activity of TF1 or the TF1.ADP complex measured with a short reaction period, 6.5, was lower than the reported value, 9.0, under the steady-state condition. Although the bound ADP was released from the complex only when the enzyme underwent multiple catalytic turnover, the rate of this release was much slower than the turnover. These results suggest that when one ADP binds to a site on one of the beta subunits and stays there for a long time, the enzyme will change form and the bound ADP will become a special species which is not able to be directly involved in the enzyme catalysis. This binding site for ADP appears to be the first site responsible for the single-site catalysis reaction observed for native TF1.

Interplay of Mg2+, ADP, and ATP in the cytosol and mitochondria: Unravelling the role of Mg2+ in cell respiration

PubMed Central

Gout, Elisabeth; Rébeillé, Fabrice; Douce, Roland; Bligny, Richard

2014-01-01

In animal and plant cells, the ATP/ADP ratio and/or energy charge are generally considered key parameters regulating metabolism and respiration. The major alternative issue of whether the cytosolic and mitochondrial concentrations of ADP and ATP directly mediate cell respiration remains unclear, however. In addition, because only free nucleotides are exchanged by the mitochondrial ADP/ATP carrier, whereas MgADP is the substrate of ATP synthase (EC 3.6.3.14), the cytosolic and mitochondrial Mg2+ concentrations must be considered as well. Here we developed in vivo/in vitro techniques using 31P-NMR spectroscopy to simultaneously measure these key components in subcellular compartments. We show that heterotrophic sycamore (Acer pseudoplatanus L.) cells incubated in various nutrient media contain low, stable cytosolic ADP and Mg2+ concentrations, unlike ATP. ADP is mainly free in the cytosol, but complexed by Mg2+ in the mitochondrial matrix, where [Mg2+] is tenfold higher. In contrast, owing to a much higher affinity for Mg2+, ATP is mostly complexed by Mg2+ in both compartments. Mg2+ starvation used to alter cytosolic and mitochondrial [Mg2+] reversibly increases free nucleotide concentration in the cytosol and matrix, enhances ADP at the expense of ATP, decreases coupled respiration, and stops cell growth. We conclude that the cytosolic ADP concentration, and not ATP, ATP/ADP ratio, or energy charge, controls the respiration of plant cells. The Mg2+ concentration, remarkably constant and low in the cytosol and tenfold higher in the matrix, mediates ADP/ATP exchange between the cytosol and matrix, [MgADP]-dependent mitochondrial ATP synthase activity, and cytosolic free ADP homeostasis. PMID:25313036

Interplay of Mg2+, ADP, and ATP in the cytosol and mitochondria: unravelling the role of Mg2+ in cell respiration.

PubMed

Gout, Elisabeth; Rébeillé, Fabrice; Douce, Roland; Bligny, Richard

2014-10-28

In animal and plant cells, the ATP/ADP ratio and/or energy charge are generally considered key parameters regulating metabolism and respiration. The major alternative issue of whether the cytosolic and mitochondrial concentrations of ADP and ATP directly mediate cell respiration remains unclear, however. In addition, because only free nucleotides are exchanged by the mitochondrial ADP/ATP carrier, whereas MgADP is the substrate of ATP synthase (EC 3.6.3.14), the cytosolic and mitochondrial Mg(2+) concentrations must be considered as well. Here we developed in vivo/in vitro techniques using (31)P-NMR spectroscopy to simultaneously measure these key components in subcellular compartments. We show that heterotrophic sycamore (Acer pseudoplatanus L.) cells incubated in various nutrient media contain low, stable cytosolic ADP and Mg(2+) concentrations, unlike ATP. ADP is mainly free in the cytosol, but complexed by Mg(2+) in the mitochondrial matrix, where [Mg(2+)] is tenfold higher. In contrast, owing to a much higher affinity for Mg(2+), ATP is mostly complexed by Mg(2+) in both compartments. Mg(2+) starvation used to alter cytosolic and mitochondrial [Mg(2+)] reversibly increases free nucleotide concentration in the cytosol and matrix, enhances ADP at the expense of ATP, decreases coupled respiration, and stops cell growth. We conclude that the cytosolic ADP concentration, and not ATP, ATP/ADP ratio, or energy charge, controls the respiration of plant cells. The Mg(2+) concentration, remarkably constant and low in the cytosol and tenfold higher in the matrix, mediates ADP/ATP exchange between the cytosol and matrix, [MgADP]-dependent mitochondrial ATP synthase activity, and cytosolic free ADP homeostasis.

49 CFR 659.21 - System security plan: general requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false System security plan: general requirements. 659.21... State Oversight Agency § 659.21 System security plan: general requirements. (a) The oversight agency shall require the rail transit agency to implement a system security plan that, at a minimum, complies...

Comparative evaluation of Plateletworks, Multiplate analyzer and Platelet function analyzer-200 in cardiology patients.

PubMed

Kim, Jeeyong; Cho, Chi Hyun; Jung, Bo Kyeung; Nam, Jeonghun; Seo, Hong Seog; Shin, Sehyun; Lim, Chae Seung

2018-04-14

The objective of this study was to comparatively evaluate three commercial whole-blood platelet function analyzer systems: Platelet Function Analyzer-200 (PFA; Siemens Canada, Mississauga, Ontario, Canada), Multiplate analyzer (MP; Roche Diagnostics International Ltd., Rotkreuz, Switzerland), and Plateletworks Combo-25 kit (PLW; Helena Laboratories, Beaumont, TX, USA). Venipuncture was performed on 160 patients who visited a department of cardiology. Pairwise agreement among the three platelet function assays was assessed using Cohen's kappa coefficient and percent agreement within the reference limit. Kappa values with the same agonists were poor between PFA-collagen (COL; agonist)/adenosine diphosphate (ADP) and MP-ADP (-0.147), PFA-COL/ADP and PLW-ADP (0.089), MP-ADP and PLW-ADP (0.039), PFA-COL/ADP and MP-COL (-0.039), and between PFA-COL/ADP and PLW-COL (-0.067). Nonetheless, kappa values for the same assay principle with a different agonist were slightly higher between PFA-COL/ADP and PFA-COL/EPI (0.352), MP-ADP and MP-COL (0.235), and between PLW-ADP and PLW-COL (0.247). The range of percent agreement values was 38.7% to 73.8%. Therefore, various measurements of platelet function by more than one method were needed to obtain a reliable interpretation of platelet function considering low kappa coefficient and modest percent agreement rates among 3 different platelet function tests.

An Organization Design for the PERSPAY Consolidated Data Center.

DTIC Science & Technology

1983-06-01

GENERAL 25 B. PROGRAM DEVELOPMENT 30 C. COMPUTER OPERATIONS 33 D. TECHNICAL SUPPORT BRANCH 36 E. MANAGEMENT OF THE D.P. ORGANIZATION...support, and 4) management , including planning, administration, and control ( Brandon , Norton Gaydasch, Frank). The following list shows the... Management policy on just what the ADP installation is expected to do is an information requirement that must be satisfied in order for the operation to

Unifying mechanism for Aplysia ADP-ribosyl cyclase and CD38/NAD(+) glycohydrolases.

PubMed Central

Cakir-Kiefer, C; Muller-Steffner, H; Schuber, F

2000-01-01

Highly purified Aplysia californica ADP-ribosyl cyclase was found to be a multifunctional enzyme. In addition to the known transformation of NAD(+) into cADP-ribose this enzyme is able to catalyse the solvolysis (hydrolysis and methanolysis) of cADP-ribose. This cADP-ribose hydrolase activity, which becomes detectable only at high concentrations of the enzyme, is amplified with analogues such as pyridine adenine dinucleotide, in which the cleavage rate of the pyridinium-ribose bond is much reduced compared with NAD(+). Although the specificity ratio V(max)/K(m) is in favour of NAD(+) by 4 orders of magnitude, this multifunctionality allowed us to propose a 'partitioning' reaction scheme for the Aplysia enzyme, similar to that established previously for mammalian CD38/NAD(+) glycohydrolases. This mechanism involves the formation of a single oxocarbenium-type intermediate that partitions to cADP-ribose and solvolytic products via competing pathways. In favour of this mechanism was the finding that the enzyme also catalysed the hydrolysis of NMN(+), a substrate that cannot undergo cyclization. The major difference between the mammalian and the invertebrate enzymes resides in their relative cyclization/hydrolysis rate-constant ratios, which dictate their respective yields of cADP-ribose (ADP-ribosyl cyclase activity) and ADP-ribose (NAD(+) glycohydrolase activity). For the Aplysia enzyme's catalysed transformation of NAD(+) we favour a mechanism where the formation of cADP-ribose precedes that of ADP-ribose; i.e. macroscopically the invertebrate ADP-ribosyl cyclase conforms to a sequential reaction pathway as a limiting form of the partitioning mechanism. PMID:10861229

Early versus delayed invasive strategy for intermediate- and high-risk acute coronary syndromes managed without P2Y12 receptor inhibitor pretreatment: Design and rationale of the EARLY randomized trial.

PubMed

Lemesle, Gilles; Laine, Marc; Pankert, Mathieu; Puymirat, Etienne; Cuisset, Thomas; Boueri, Ziad; Maillard, Luc; Armero, Sébastien; Cayla, Guillaume; Bali, Laurent; Motreff, Pascal; Peyre, Jean-Pascal; Paganelli, Franck; Kerbaul, François; Roch, Antoine; Michelet, Pierre; Baumstarck, Karine; Bonello, Laurent

2018-01-01

According to recent literature, pretreatment with a P2Y 12 ADP receptor antagonist before coronary angiography appears no longer suitable in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) due to an unfavorable risk-benefit ratio. Optimal delay of the invasive strategy in this specific context is unknown. We hypothesize that without P2Y 12 ADP receptor antagonist pretreatment, a very early invasive strategy may be beneficial. The EARLY trial (Early or Delayed Revascularization for Intermediate- and High-Risk Non-ST-Segment Elevation Acute Coronary Syndromes?) is a prospective, multicenter, randomized, controlled, open-label, 2-parallel-group study that plans to enroll 740 patients. Patients are eligible if the diagnosis of intermediate- or high-risk NSTE-ACS is made and an invasive strategy intended. Patients are randomized in a 1:1 ratio. In the control group, a delayed strategy is adopted, with the coronary angiography taking place between 12 and 72 hours after randomization. In the experimental group, a very early invasive strategy is performed within 2 hours. A loading dose of a P2Y 12 ADP receptor antagonist is given at the time of intervention in both groups. Recruitment began in September 2016 (n = 558 patients as of October 2017). The primary endpoint is the composite of cardiovascular death and recurrent ischemic events at 1 month. The EARLY trial aims to demonstrate the superiority of a very early invasive strategy compared with a delayed strategy in intermediate- and high-risk NSTE-ACS patients managed without P2Y 12 ADP receptor antagonist pretreatment. © 2018 Wiley Periodicals, Inc.

Nucleolar-nucleoplasmic shuttling of TARG1 and its control by DNA damage-induced poly-ADP-ribosylation and by nucleolar transcription.

PubMed

Bütepage, Mareike; Preisinger, Christian; von Kriegsheim, Alexander; Scheufen, Anja; Lausberg, Eva; Li, Jinyu; Kappes, Ferdinand; Feederle, Regina; Ernst, Sabrina; Eckei, Laura; Krieg, Sarah; Müller-Newen, Gerhard; Rossetti, Giulia; Feijs, Karla L H; Verheugd, Patricia; Lüscher, Bernhard

2018-04-30

Macrodomains are conserved protein folds associated with ADP-ribose binding and turnover. ADP-ribosylation is a posttranslational modification catalyzed primarily by ARTD (aka PARP) enzymes in cells. ARTDs transfer either single or multiple ADP-ribose units to substrates, resulting in mono- or poly-ADP-ribosylation. TARG1/C6orf130 is a macrodomain protein that hydrolyzes mono-ADP-ribosylation and interacts with poly-ADP-ribose chains. Interactome analyses revealed that TARG1 binds strongly to ribosomes and proteins associated with rRNA processing and ribosomal assembly factors. TARG1 localized to transcriptionally active nucleoli, which occurred independently of ADP-ribose binding. TARG1 shuttled continuously between nucleoli and nucleoplasm. In response to DNA damage, which activates ARTD1/2 (PARP1/2) and promotes synthesis of poly-ADP-ribose chains, TARG1 re-localized to the nucleoplasm. This was dependent on the ability of TARG1 to bind to poly-ADP-ribose. These findings are consistent with the observed ability of TARG1 to competitively interact with RNA and PAR chains. We propose a nucleolar role of TARG1 in ribosome assembly or quality control that is stalled when TARG1 is re-located to sites of DNA damage.

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

PubMed Central

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

45 CFR 164.318 - Compliance dates for the initial implementation of the security standards.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the security standards. 164.318 Section 164.318 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES ADMINISTRATIVE DATA STANDARDS AND RELATED REQUIREMENTS SECURITY AND PRIVACY Security Standards for the Protection... of the security standards. (a) Health plan. (1) A health plan that is not a small health plan must...

Effect of ADP on slow-twitch muscle fibres of the rat: implications for muscle fatigue.

PubMed

Macdonald, W A; Stephenson, D G

2006-05-15

Slow-twitch mechanically skinned fibres from rat soleus muscle were bathed in solutions mimicking the myoplasmic environment but containing different [ADP] (0.1 microm to 1.0 mm). The effect of ADP on sarcoplasmic reticulum (SR) Ca2+-content was determined from the magnitude of caffeine-induced force responses, while temporal changes in SR Ca2+-content allowed determination of the effective rates of the SR Ca2+-pump and of the SR Ca2+-leak. The SR Ca2+-pump rate, estimated at pCa (-log10[Ca2+]) 7.8, was reduced by 20% as the [ADP] was increased from 0.1 to 40 microm, with no further alteration when the [ADP] was increased to 1.0 mm. The SR Ca2+-leak rate constant was not altered by increasing [ADP] from 0.1 to 40 microm, but was increased by 26% when the [ADP] was elevated to 1.0 mm. This ADP-induced SR Ca2+-leak was insensitive to ruthenium red but was abolished by 2,5-di(tert-butyl)-1,4-hydroquinone (TBQ), indicating that the leak pathway is via the SR Ca2+-pump and not the SR Ca2+-release channel. The decrease in SR Ca2+-pump rate and SR Ca2+-leak rate when [ADP] was increased led to a 40% decrease in SR Ca2+-loading capacity. Elevation of [ADP] had only minor direct effects on the contractile apparatus of slow-twitch fibres. These results suggest that ADP has only limited depressing effects on the contractility of slow-twitch muscle fibres. This is in contrast to the marked effects of ADP on force responses in fast-twitch muscle fibres and may contribute to the fatigue-resistant nature of slow-twitch muscle fibres.

Adenosine diphosphate-induced platelet-fibrin clot strength: a new thrombelastographic indicator of long-term poststenting ischemic events.

PubMed

Gurbel, Paul A; Bliden, Kevin P; Navickas, Irene A; Mahla, Elizabeth; Dichiara, Joseph; Suarez, Thomas A; Antonino, Mark J; Tantry, Udaya S; Cohen, Eli

2010-08-01

Poststenting ischemic events occur despite dual-antiplatelet therapy, suggesting that a "one size fits all" antithrombotic strategy has significant limitations. Ex vivo platelet function measurements may facilitate risk stratification and personalized antiplatelet therapy. We investigated the prognostic utility of the strength of adenosine diphosphate (ADP)-induced (MA(ADP)) and thrombin-induced (MA(THROMBIN)) platelet-fibrin clots measured by thrombelastography and ADP-induced light transmittance aggregation (LTA(ADP)) in 225 serial patients after elective stenting treated with aspirin and clopidogrel. Ischemic and bleeding events were assessed over 3 years. Overall, 59 (26%) first ischemic events occurred. Patients with ischemic events had higher MA(ADP), MA(THROMBIN), and LTA(ADP) (P < .0001 for all comparisons). By receiver operating characteristic curve analysis, MA(ADP) >47 mm had the best predictive value of long-term ischemic events compared with other measurements (P < .0001), with an area under the curve = 0.84 (95% CI 0.78-0.89, P < .0001). The univariate Cox proportional hazards model identified MA(ADP) >47 mm, MA(THROMBIN) >69 mm, and LTA(ADP) >34% as significant independent predictors of first ischemic events at the 3-year time point, with hazard ratios of 10.3 (P < .0001), 3.8 (P < .0001), and 4.8 (P < .0001), respectively. Fifteen bleeding events occurred. Receiver operating characteristic curve and quartile analysis suggests MA(ADP)

In the absence of phosphate shuttling, exercise reveals the in vivo importance of creatine-independent mitochondrial ADP transport.

PubMed

Miotto, Paula M; Holloway, Graham P

2016-09-15

The transport of cytosolic adenosine diphosphate (ADP) into the mitochondria is a major control point in metabolic homeostasis, as ADP concentrations directly affect glycolytic flux and oxidative phosphorylation rates within mitochondria. A large contributor to the efficiency of this process is thought to involve phosphocreatine (PCr)/Creatine (Cr) shuttling through mitochondrial creatine kinase (Mi-CK), whereas the biological importance of alterations in Cr-independent ADP transport during exercise remains unknown. Therefore, we utilized an Mi-CK knockout (KO) model to determine whether in vivo Cr-independent mechanisms are biologically important for sustaining energy homeostasis during exercise. Ablating Mi-CK did not alter exercise tolerance, as the time to volitional fatigue was similar between wild-type (WT) and KO mice at various exercise intensities. In addition, skeletal muscle metabolic profiles after exercise, including glycogen, PCr/Cr ratios, free ADP/adenosine monophosphate (AMP), and lactate, were similar between genotypes. While these data suggest that the absence of PCr/Cr shuttling is not detrimental to maintaining energy homeostasis during exercise, KO mice displayed a dramatic increase in Cr-independent mitochondrial ADP sensitivity after exercise. Specifically, whereas mitochondrial ADP sensitivity decreased with exercise in WT mice, in stark contrast, exercise increased mitochondrial Cr-independent ADP sensitivity in KO mice. As a result, the apparent ADP Km was 50% lower in KO mice after exercise, suggesting that in vivo activation of voltage-dependent anion channel (VDAC)/adenine nucleotide translocase (ANT) can support mitochondrial ADP transport. Altogether, we provide insight that Cr-independent ADP transport mechanisms are biologically important for regulating ADP sensitivity during exercise, while highlighting complex regulation and the plasticity of the VDAC/ANT axis to support adenosine triphosphate demand. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Molecular Bases of Catalysis and ADP-Ribose Preference of Human Mn2+-Dependent ADP-Ribose/CDP-Alcohol Diphosphatase and Conversion by Mutagenesis to a Preferential Cyclic ADP-Ribose Phosphohydrolase

PubMed Central

Cabezas, Alicia; Ribeiro, João Meireles; Rodrigues, Joaquim Rui; López-Villamizar, Iralis; Fernández, Ascensión; Canales, José; Pinto, Rosa María; Costas, María Jesús; Cameselle, José Carlos

2015-01-01

Among metallo-dependent phosphatases, ADP-ribose/CDP-alcohol diphosphatases form a protein family (ADPRibase-Mn-like) mainly restricted, in eukaryotes, to vertebrates and plants, with preferential expression, at least in rodents, in immune cells. Rat and zebrafish ADPRibase-Mn, the only biochemically studied, are phosphohydrolases of ADP-ribose and, somewhat less efficiently, of CDP-alcohols and 2´,3´-cAMP. Furthermore, the rat but not the zebrafish enzyme displays a unique phosphohydrolytic activity on cyclic ADP-ribose. The molecular basis of such specificity is unknown. Human ADPRibase-Mn showed similar activities, including cyclic ADP-ribose phosphohydrolase, which seems thus common to mammalian ADPRibase-Mn. Substrate docking on a homology model of human ADPRibase-Mn suggested possible interactions of ADP-ribose with seven residues located, with one exception (Cys253), either within the metallo-dependent phosphatases signature (Gln27, Asn110, His111), or in unique structural regions of the ADPRibase-Mn family: s2s3 (Phe37 and Arg43) and h7h8 (Phe210), around the active site entrance. Mutants were constructed, and kinetic parameters for ADP-ribose, CDP-choline, 2´,3´-cAMP and cyclic ADP-ribose were determined. Phe37 was needed for ADP-ribose preference without catalytic effect, as indicated by the increased ADP-ribose K m and unchanged k cat of F37A-ADPRibase-Mn, while the K m values for the other substrates were little affected. Arg43 was essential for catalysis as indicated by the drastic efficiency loss shown by R43A-ADPRibase-Mn. Unexpectedly, Cys253 was hindering for cADPR phosphohydrolase, as indicated by the specific tenfold gain of efficiency of C253A-ADPRibase-Mn with cyclic ADP-ribose. This allowed the design of a triple mutant (F37A+L196F+C253A) for which cyclic ADP-ribose was the best substrate, with a catalytic efficiency of 3.5´104 M-1s-1 versus 4´103 M-1s-1 of the wild type. PMID:25692488

ADP--A Must in the Secondary School

ERIC Educational Resources Information Center

Majernik, John A.

1974-01-01

The rationale for including automated data processing (ADP) in secondary schools is given. ADP instruction: prepares students for data processing employment and for advanced ADP study, aids all students preparing for business careers, aids students in choosing a career, provides consumer information, and adds realism to other classroom…

The role of ADP-ribosylation in regulating DNA interstrand crosslink repair

PubMed Central

Gunn, Alasdair R.; Banos-Pinero, Benito; Paschke, Peggy; Sanchez-Pulido, Luis; Ariza, Antonio; Day, Joseph; Emrich, Mehera; Leys, David; Ponting, Chris P.

2016-01-01

ABSTRACT ADP-ribosylation by ADP-ribosyltransferases (ARTs) has a well-established role in DNA strand break repair by promoting enrichment of repair factors at damage sites through ADP-ribose interaction domains. Here, we exploit the simple eukaryote Dictyostelium to uncover a role for ADP-ribosylation in regulating DNA interstrand crosslink repair and redundancy of this pathway with non-homologous end-joining (NHEJ). In silico searches were used to identify a protein that contains a permutated macrodomain (which we call aprataxin/APLF-and-PNKP-like protein; APL). Structural analysis reveals that this permutated macrodomain retains features associated with ADP-ribose interactions and that APL is capable of binding poly(ADP-ribose) through this macrodomain. APL is enriched in chromatin in response to cisplatin treatment, an agent that induces DNA interstrand crosslinks (ICLs). This is dependent on the macrodomain of APL and the ART Adprt2, indicating a role for ADP-ribosylation in the cellular response to cisplatin. Although adprt2− cells are sensitive to cisplatin, ADP-ribosylation is evident in these cells owing to redundant signalling by the double-strand break (DSB)-responsive ART Adprt1a, promoting NHEJ-mediated repair. These data implicate ADP-ribosylation in DNA ICL repair and identify that NHEJ can function to resolve this form of DNA damage in the absence of Adprt2. PMID:27587838

Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats

NASA Astrophysics Data System (ADS)

Wang, Liye; Huang, Lingli; Pan, Yuanhu; Kuča, Kamil; Klímová, Blanka; Wu, Qinghua; Xie, Shuyu; Ahmad, Ijaz; Chen, Dongmei; Tao, Yanfei; Wan, Dan; Liu, Zhenli; Yuan, Zonghui

2016-02-01

Aditoprim (ADP) is a newly developed antibacterial agent in veterinary medicine. The metabolism and disposition of ADP in swine, broilers, carp and rats were investigated by using a radio tracer method combined with a radioactivity detector and a liquid chromatography/ion trap/time-of-flight mass spectrometry. After a single oral administration, more than 94% of the dose was recovered within 14 d in the four species. The urine excretion was dominant in swine and rats, making up 78% of the dose. N-monodesmethyl-ADP, N-didesmethyl-ADP, and 10 new metabolites were characterized. These metabolites were biotransformed from the process of demethylation, α-hydroxylation, N-oxidation, and NH2-glucuronidation. After an oral dose for 7 d, ADP-derived radioactivity was widely distributed in tissues, and high concentrations were especially observed in bile, liver, kidney, lung, and spleen. The radioactivity in the liver was eliminated much more slowly than in other tissues, with a half-life of 4.26, 3.38, 6.69, and 5.21 d in swine, broilers, carp, and rats, respectively. ADP, N-monodesmethyl-ADP, and N-didesmethyl-ADP were the major metabolites in edible tissues. Notably, ADP was detected with the highest concentration and the longest duration in these tissues. These findings indicated that ADP is the marker residue and the liver is the residue target tissue.

Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats

PubMed Central

Wang, Liye; Huang, Lingli; Pan, Yuanhu; Kuča, Kamil; Klímová, Blanka; Wu, Qinghua; Xie, Shuyu; Ahmad, Ijaz; Chen, Dongmei; Tao, Yanfei; Wan, Dan; Liu, Zhenli; Yuan, Zonghui

2016-01-01

Aditoprim (ADP) is a newly developed antibacterial agent in veterinary medicine. The metabolism and disposition of ADP in swine, broilers, carp and rats were investigated by using a radio tracer method combined with a radioactivity detector and a liquid chromatography/ion trap/time-of-flight mass spectrometry. After a single oral administration, more than 94% of the dose was recovered within 14 d in the four species. The urine excretion was dominant in swine and rats, making up 78% of the dose. N-monodesmethyl-ADP, N-didesmethyl-ADP, and 10 new metabolites were characterized. These metabolites were biotransformed from the process of demethylation, α-hydroxylation, N-oxidation, and NH2-glucuronidation. After an oral dose for 7 d, ADP-derived radioactivity was widely distributed in tissues, and high concentrations were especially observed in bile, liver, kidney, lung, and spleen. The radioactivity in the liver was eliminated much more slowly than in other tissues, with a half-life of 4.26, 3.38, 6.69, and 5.21 d in swine, broilers, carp, and rats, respectively. ADP, N-monodesmethyl-ADP, and N-didesmethyl-ADP were the major metabolites in edible tissues. Notably, ADP was detected with the highest concentration and the longest duration in these tissues. These findings indicated that ADP is the marker residue and the liver is the residue target tissue. PMID:26838160

33 CFR 104.405 - Format of the Vessel Security Plan (VSP).

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Communications; (9) Security systems and equipment maintenance; (10) Security measures for access control... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Format of the Vessel Security... SECURITY MARITIME SECURITY MARITIME SECURITY: VESSELS Vessel Security Plan (VSP) § 104.405 Format of the...

Body-density measurement in children: the BOD POD versus Hydrodensitometry.

PubMed

Holmes, Jason C; Gibson, Ann L; Cremades, J Gualberto; Mier, Constance M

2011-06-01

To compare estimates of body density (Db) from air-displacement plethysmography (ADP) with measured and predicted thoracic-gas-volume (TGV) measurements and those from hydrodensitometry (HD) in children. Seventeen participants (13 male and 4 female; 10.1 ± 2.20 yr, 42.0 ± 15.03 kg, 145.6 ± 17.41 cm, 30.0 ± 8.66 kg/m²) were tested using ADP and HD, with ADP always preceding HD. Db estimates were compared between ADP with measured TGV, ADP with predicted TGV, and the reference measure, HD. Regression analyses were used to assess the accuracy of the ADP methods, and potential bias between the ADP procedures and HD were evaluated using Bland-Altman analyses. The cross-validation criteria described by Lohman for estimating Db relative to HD were used to interpret the results of the study. A significant difference was found between Db estimates from ADP with measured TGV (1.0453 ± 0.01934 g/cm³) and ADP with predicted TGV (1.0415 ± 0.01858 g/cm³); however, neither was significantly different from Db obtained by the reference HD procedure (1.0417 ± 0.02391 g/cm³). For both ADP procedures, regression analyses produced an r = .737-.738, r² = .543-.544, and SEE = 0.02 g/cm³, and the regression lines deviated significantly from the line of identity; however, no significant biases were indicated. Despite no significant mean differences between Db estimates from the ADP procedures and HD, more cross-validation research is needed before recommending the BOD POD for routine use with children in clinical and research settings.

Dual functional bioactive-peptide, AIMP1-derived peptide (AdP), for anti-aging.

PubMed

Kim, Jina; Kang, Sujin; Kwon, HanJin; Moon, HoSang; Park, Min Chul

2018-06-19

Human skin aging is caused by several factors, such as UV irradiation, stress, hormone, and pollution. Wrinkle formation and skin pigmentation are representative features of skin aging. Although EGF and arbutin are used as anti-wrinkle and skin whitening agents, respectively, they have adverse effects on skin. When more cosmeceutical ingredients are added to cosmetic product, adverse effects are also accumulated. For these reasons, multifunctional and safe cosmetic ingredients are in demand. The aim of the present study is to investigate the novel anti-aging agents, AIMP1-derived peptide (AdP, INCI name: sh-oligopeptide-5/sh-oligopeptide SP) for cosmetic products. To assess the anti-wrinkle effect of AdP, collagen type I synthesis and fibroblast proliferation were determined on human fibroblasts. The anti-wrinkle effect of AdP was examined by ELISA and cell titer glo assay. To assess the whitening, melanin content and tyrosinase activity were determined on melanocytes. The whitening effect of AdP was examined by melanin measurement and enzyme activity assay. The safety of AdP was determined by cytotoxicity and immunogenicity, CCK-8 and TNF-α ELISA assay, respectively. AdP treatment induced the collagen type I synthesis and fibroblast proliferation. Also, AdP treatment inhibited melanin synthesis by regulating tyrosinase activity. The anti-aging effect of AdP is more potent than EGF and albutin. AdP did not show adverse effects. These results show that AdP can be dual functional and safe cosmeceutical agent to prevent skin aging. © 2018 Wiley Periodicals, Inc.

Automatic Data Processing Equipment (ADPE) acquisition plan for the medical sciences

NASA Technical Reports Server (NTRS)

1979-01-01

An effective mechanism for meeting the SLSD/MSD data handling/processing requirements for Shuttle is discussed. The ability to meet these requirements depends upon the availability of a general purpose high speed digital computer system. This system is expected to implement those data base management and processing functions required across all SLSD/MSD programs during training, laboratory operations/analysis, simulations, mission operations, and post mission analysis/reporting.

33 CFR 106.405 - Format and content of the Facility Security Plan (FSP).

Code of Federal Regulations, 2010 CFR

2010-07-01

...; (9) Security systems and equipment maintenance; (10) Security measures for access control; (11... Facility Security Plan (FSP). 106.405 Section 106.405 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MARITIME SECURITY MARINE SECURITY: OUTER CONTINENTAL SHELF (OCS) FACILITIES...

Studying Catabolism of Protein ADP-Ribosylation.

PubMed

Palazzo, Luca; James, Dominic I; Waddell, Ian D; Ahel, Ivan

2017-01-01

Protein ADP-ribosylation is a conserved posttranslational modification that regulates many major cellular functions, such as DNA repair, transcription, translation, signal transduction, stress response, cell division, aging, and cell death. Protein ADP-ribosyl transferases catalyze the transfer of an ADP-ribose (ADPr) group from the β-nicotinamide adenine dinucleotide (β-NAD + ) cofactor onto a specific target protein with the subsequent release of nicotinamide. ADP-ribosylation leads to changes in protein structure, function, stability, and localization, thus defining the appropriate cellular response. Signaling processes that are mediated by modifications need to be finely tuned and eventually silenced and one of the ways to achieve this is through the action of enzymes that remove (reverse) protein ADP-ribosylation in a timely fashion such as PARG, TARG1, MACROD1, and MACROD2. Here, we describe several basic methods used to study the enzymatic activity of de-ADP-ribosylating enzymes.

Crystal structures of the ATP-binding and ADP-release dwells of the V1 rotary motor

PubMed Central

Suzuki, Kano; Mizutani, Kenji; Maruyama, Shintaro; Shimono, Kazumi; Imai, Fabiana L.; Muneyuki, Eiro; Kakinuma, Yoshimi; Ishizuka-Katsura, Yoshiko; Shirouzu, Mikako; Yokoyama, Shigeyuki; Yamato, Ichiro; Murata, Takeshi

2016-01-01

V1-ATPases are highly conserved ATP-driven rotary molecular motors found in various membrane systems. We recently reported the crystal structures for the Enterococcus hirae A3B3DF (V1) complex, corresponding to the catalytic dwell state waiting for ATP hydrolysis. Here we present the crystal structures for two other dwell states obtained by soaking nucleotide-free V1 crystals in ADP. In the presence of 20 μM ADP, two ADP molecules bind to two of three binding sites and cooperatively induce conformational changes of the third site to an ATP-binding mode, corresponding to the ATP-binding dwell. In the presence of 2 mM ADP, all nucleotide-binding sites are occupied by ADP to induce conformational changes corresponding to the ADP-release dwell. Based on these and previous findings, we propose a V1-ATPase rotational mechanism model. PMID:27807367

Inhibiting poly(ADP-ribosylation) improves axon regeneration.

PubMed

Byrne, Alexandra B; McWhirter, Rebecca D; Sekine, Yuichi; Strittmatter, Stephen M; Miller, David M; Hammarlund, Marc

2016-10-04

The ability of a neuron to regenerate its axon after injury depends in part on its intrinsic regenerative potential. Here, we identify novel intrinsic regulators of axon regeneration: poly(ADP-ribose) glycohodrolases (PARGs) and poly(ADP-ribose) polymerases (PARPs). PARGs, which remove poly(ADP-ribose) from proteins, act in injured C. elegans GABA motor neurons to enhance axon regeneration. PARG expression is regulated by DLK signaling, and PARGs mediate DLK function in enhancing axon regeneration. Conversely, PARPs, which add poly(ADP-ribose) to proteins, inhibit axon regeneration of both C. elegans GABA neurons and mammalian cortical neurons. Furthermore, chemical PARP inhibitors improve axon regeneration when administered after injury. Our results indicate that regulation of poly(ADP-ribose) levels is a critical function of the DLK regeneration pathway, that poly-(ADP ribosylation) inhibits axon regeneration across species, and that chemical inhibition of PARPs can elicit axon regeneration.

Inhibiting poly(ADP-ribosylation) improves axon regeneration

PubMed Central

Byrne, Alexandra B; McWhirter, Rebecca D; Sekine, Yuichi; Strittmatter, Stephen M; Miller, David M; Hammarlund, Marc

2016-01-01

The ability of a neuron to regenerate its axon after injury depends in part on its intrinsic regenerative potential. Here, we identify novel intrinsic regulators of axon regeneration: poly(ADP-ribose) glycohodrolases (PARGs) and poly(ADP-ribose) polymerases (PARPs). PARGs, which remove poly(ADP-ribose) from proteins, act in injured C. elegans GABA motor neurons to enhance axon regeneration. PARG expression is regulated by DLK signaling, and PARGs mediate DLK function in enhancing axon regeneration. Conversely, PARPs, which add poly(ADP-ribose) to proteins, inhibit axon regeneration of both C. elegans GABA neurons and mammalian cortical neurons. Furthermore, chemical PARP inhibitors improve axon regeneration when administered after injury. Our results indicate that regulation of poly(ADP-ribose) levels is a critical function of the DLK regeneration pathway, that poly-(ADP ribosylation) inhibits axon regeneration across species, and that chemical inhibition of PARPs can elicit axon regeneration. DOI: http://dx.doi.org/10.7554/eLife.12734.001 PMID:27697151

29 CFR 2509.75-3 - Interpretive bulletin relating to investments by employee benefit plans in securities of...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR... Interpretive bulletin relating to investments by employee benefit plans in securities of registered investment.... That section provides that an investment by an employee benefit plan in securities issued by an...

49 CFR 1542.301 - Contingency plan.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Contingency plan. 1542.301 Section 1542.301..., DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Contingency Measures § 1542.301 Contingency plan. (a) Each airport operator required to have a security program under § 1542.103(a) and (b...

Load-dependent ADP binding to myosins V and VI: Implications for subunit coordination and function

PubMed Central

Oguchi, Yusuke; Mikhailenko, Sergey V.; Ohki, Takashi; Olivares, Adrian O.; De La Cruz, Enrique M.; Ishiwata, Shin'ichi

2008-01-01

Dimeric myosins V and VI travel long distances in opposite directions along actin filaments in cells, taking multiple steps in a “hand-over-hand” fashion. The catalytic cycles of both myosins are limited by ADP dissociation, which is considered a key step in the walking mechanism of these motors. Here, we demonstrate that external loads applied to individual actomyosin V or VI bonds asymmetrically affect ADP affinity, such that ADP binds weaker under loads assisting motility. Model-based analysis reveals that forward and backward loads modulate the kinetics of ADP binding to both myosins, although the effect is less pronounced for myosin VI. ADP dissociation is modestly accelerated by forward loads and inhibited by backward loads. Loads applied in either direction slow ADP binding to myosin V but accelerate binding to myosin VI. We calculate that the intramolecular load generated during processive stepping is ≈2 pN for both myosin V and myosin VI. The distinct load dependence of ADP binding allows these motors to perform different cellular functions. PMID:18509050

33 CFR 103.520 - Recordkeeping.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 103.520 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MARITIME SECURITY MARITIME SECURITY: AREA MARITIME SECURITY Area Maritime Security (AMS) Plan § 103.520 Recordkeeping. (a) All records pertaining to the Area Maritime Security (AMS) Assessment and AMS Plan will be retained by...

Regulation of mitochondrial energy production in cardiac cells of rainbow trout (Oncorhynchus mykiss).

PubMed

Birkedal, R; Gesser, H

2004-04-01

In skinned rat cardiac fibres, mitochondrial affinity for endogenous ADP generated by creatine kinase and Ca2+-activated ATPases is higher than for exogenous ADP added to the surrounding medium, suggesting that mitochondria are functionally coupled to creatine kinase and ATPases. Such a coupling may be weaker or absent in ectothermic vertebrate cardiac cells, because they typically have less elaborate intracellular membrane structures, higher glycolytic capacity and lower working temperature. Therefore, we examined skinned cardiac fibres from rainbow trout at 10 degrees C. The apparent mitochondrial affinity for endogenous ADP was obtained by stimulation with ATP and recording of the release of ADP into the surrounding medium. The apparent affinity for endogenous ADP was much higher than for exogenous ADP suggesting a functional coupling between mitochondria and ATPases. The apparent affinity for exogenous ADP and ATP was increased by creatine or an increase in Ca2+-activity, which should increase intrafibrillar turnover of ATP to ADP. In conclusion, ADP seems to be channelled from creatine kinase and ATPases to mitochondria without being released to the surrounding medium. Thus, despite difference in structure, temperature and metabolic capacity, trout myocardium resembles that of rat with regard to the regulation of mitochondrial respiration. Copyright 2004 Springer-Verlag

Hydrofluoric Acid-Based Derivatization Strategy To Profile PARP-1 ADP-Ribosylation by LC-MS/MS.

PubMed

Gagné, Jean-Philippe; Langelier, Marie-France; Pascal, John M; Poirier, Guy G

2018-06-11

Despite significant advances in the development of mass spectrometry-based methods for the identification of protein ADP-ribosylation, current protocols suffer from several drawbacks that preclude their widespread applicability. Given the intrinsic heterogeneous nature of poly(ADP-ribose), a number of strategies have been developed to generate simple derivatives for effective interrogation of protein databases and site-specific localization of the modified residues. Currently, the generation of spectral signatures indicative of ADP-ribosylation rely on chemical or enzymatic conversion of the modification to a single mass increment. Still, limitations arise from the lability of the poly(ADP-ribose) remnant during tandem mass spectrometry, the varying susceptibilities of different ADP-ribose-protein bonds to chemical hydrolysis, or the context dependence of enzyme-catalyzed reactions. Here, we present a chemical-based derivatization method applicable to the confident identification of site-specific ADP-ribosylation by conventional mass spectrometry on any targeted amino acid residue. Using PARP-1 as a model protein, we report that treatment of ADP-ribosylated peptides with hydrofluoric acid generates a specific +132 Da mass signature that corresponds to the decomposition of mono- and poly(ADP-ribosylated) peptides into ribose adducts as a consequence of the cleavage of the phosphorus-oxygen bonds.

Acetylation-dependent ADP-ribosylation by Trypanosoma brucei Sir2.

PubMed

Kowieski, Terri M; Lee, Susan; Denu, John M

2008-02-29

Sirtuins are a highly conserved family of proteins implicated in diverse cellular processes such as gene silencing, aging, and metabolic regulation. Although many sirtuins catalyze a well characterized protein/histone deacetylation reaction, there are a number of reports that suggest protein ADP-ribosyltransferase activity. Here we explored the mechanisms of ADP-ribosylation using the Trypanosoma brucei Sir2 homologue TbSIR2rp1 as a model for sirtuins that reportedly display both activities. Steady-state kinetic analysis revealed a highly active histone deacetylase (k cat = 0.1 s(-1), with Km values of 42 microm and for NAD+ and 65 microm for acetylated substrate). A series of biochemical assays revealed that TbSIR2rp1 ADP-ribosylation of protein/histone requires an acetylated substrate. The data are consistent with two distinct ADP-ribosylation pathways that involve an acetylated substrate, NAD+ and TbSIR2rp1 as follows: 1) a noncatalytic reaction between the deacetylation product O-acetyl-ADP-ribose (or its hydrolysis product ADP-ribose) and histones, and 2) a more efficient mechanism involving interception of an ADP-ribose-acetylpeptide-enzyme intermediate by a side-chain nucleophile from bound histone. However, the sum of both ADP-ribosylation reactions was approximately 5 orders of magnitude slower than histone deacetylation under identical conditions. The biological implications of these results are discussed.

Microtubule protein ADP-ribosylation in vitro leads to assembly inhibition and rapid depolymerization

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

Scaife, R.M.; Wilson, L.; Purich, D.L.

1992-01-14

Bovine brain microtubule protein, containing both tubulin and microtubule-associated proteins, undergoes ADP-ribosylation in the presence of ({sup 14}C)NAD{sup +} and a turkey erythrocyte mono-ADP-ribosyltransferase in vitro. The modification reaction could be demonstrated in crude brain tissue extracts where selective ADP-ribosylation of both the {alpha} and {beta} chains of tubulin and of the high molecular weight microtubule-associated protein MAP-2 occurred. In experiments with purified microtubule protein, tubulin dimer, the high molecular weight microtubule-associated protein MAP-2, and another high molecular weight microtubule-associated protein which may be a MAP-1 species were heavily labeled. Tubulin and MAP-2 incorporated ({sup 14}C)ADP-ribose to an average extentmore » of approximately 2.4 and 30 mol of ADP-ribose/mol of protein, respectively. Assembly of microtubule protein into microtubules in vitro was inhibited by ADP-ribosylation, and incubation of assembled steady-state microtubules with ADP-ribosyltransferase and NAD{sup +} resulted in rapid depolymerization of the microtubules. Thus, the eukaryotic enzyme can ADP-ribosylate tubulin and microtubule-associated proteins to much greater extents than previously observed with cholera and pertussis toxins, and the modification can significantly modulate microtubule assembly and disassembly.« less

33 CFR 103.510 - Area Maritime Security (AMS) Plan review and approval.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Area Maritime Security (AMS) Plan review and approval. 103.510 Section 103.510 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF...) Plan § 103.510 Area Maritime Security (AMS) Plan review and approval. Each AMS Plan will be submitted...

Platelet reactivity to adenosine diphosphate and long-term ischemic event occurrence following percutaneous coronary intervention: a potential antiplatelet therapeutic target.

PubMed

Gurbel, Paul A; Antonino, Mark J; Bliden, Kevin P; Dichiara, Joseph; Suarez, Thomas A; Singla, Anand; Tantry, Udaya S

2008-12-01

Platelets play a central role in the genesis of post-percutaneous coronary intervention (PCI) ischemic events. High post-procedural platelet reactivity to adenosine diphosphate (HPR(ADP)) may be a risk factor for ischemic events after PCI. The study was designed to evaluate a cutpoint of platelet reactivity that is associated with the occurrence of ischemic events after PCI. Post-procedural platelet reactivity to ADP was measured by conventional aggregometry in 297 consecutive patients undergoing non-emergent PCI. Patients were prospectively followed for up to 2 years for post-discharge ischemic events. All patients had received clopidogrel and aspirin therapy at the time of aggregation measurements. Eighty-one patients (27%) suffered ischemic events. Patients with ischemic events had higher 5 microM ADP-induced platelet aggregation (46 +/- 14% vs. 30 +/- 17%, p < 0.001) and 20 microM ADP-induced platelet aggregation (60 +/- 13% vs. 43 +/- 19%, p < 0.001) compared to patients without ischemic events. Using a combined receiver operator curve analysis, cutpoints of >46% aggregation following 5 microM ADP stimulation and >59% aggregation following 20 microM ADP stimulation (HPR(ADP)) were associated with 58 and 54% of ischemic events, respectively. Multivariate Cox regression demonstrated a significant relation between event occurrence and post-procedural HPR(ADP) cutpoints (5 microM ADP, OR=3.9, and 20 microM ADP, OR=3.8, p < 0.001 for both). High post-procedural platelet reactivity to ADP is an independent risk factor for ischemic events within 2 years of non-emergent PCI. These data support a potential therapeutic target for antiplatelet therapy based on the results of an ex vivo platelet function test. The study is a step towards a personalized medicine approach to guide the intensity of antiplatelet therapy.

Development of second generation peptides modulating cellular adiponectin receptor responses

NASA Astrophysics Data System (ADS)

Otvos, Laszlo; Knappe, Daniel; Hoffmann, Ralf; Kovalszky, Ilona; Olah, Julia; Hewitson, Tim; Stawikowska, Roma; Stawikowski, Maciej; Cudic, Predrag; Lin, Feng; Wade, John; Surmacz, Eva; Lovas, Sandor

2014-10-01

The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC). In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML) cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399). The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400) was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400) at similar concentrations will be an important target validation tool to study adiponectin functions.

Effect of ADP on slow-twitch muscle fibres of the rat: implications for muscle fatigue

PubMed Central

Macdonald, W A; Stephenson, D G

2006-01-01

Slow-twitch mechanically skinned fibres from rat soleus muscle were bathed in solutions mimicking the myoplasmic environment but containing different [ADP] (0.1 μm to 1.0 mm). The effect of ADP on sarcoplasmic reticulum (SR) Ca2+-content was determined from the magnitude of caffeine-induced force responses, while temporal changes in SR Ca2+-content allowed determination of the effective rates of the SR Ca2+-pump and of the SR Ca2+-leak. The SR Ca2+-pump rate, estimated at pCa (−log10[Ca2+]) 7.8, was reduced by 20% as the [ADP] was increased from 0.1 to 40 μm, with no further alteration when the [ADP] was increased to 1.0 mm. The SR Ca2+-leak rate constant was not altered by increasing [ADP] from 0.1 to 40 μm, but was increased by 26% when the [ADP] was elevated to 1.0 mm. This ADP-induced SR Ca2+-leak was insensitive to ruthenium red but was abolished by 2,5-di(tert-butyl)-1,4-hydroquinone (TBQ), indicating that the leak pathway is via the SR Ca2+-pump and not the SR Ca2+-release channel. The decrease in SR Ca2+-pump rate and SR Ca2+-leak rate when [ADP] was increased led to a 40% decrease in SR Ca2+-loading capacity. Elevation of [ADP] had only minor direct effects on the contractile apparatus of slow-twitch fibres. These results suggest that ADP has only limited depressing effects on the contractility of slow-twitch muscle fibres. This is in contrast to the marked effects of ADP on force responses in fast-twitch muscle fibres and may contribute to the fatigue-resistant nature of slow-twitch muscle fibres. PMID:16556653

Modulation of K+ currents in Xenopus spinal neurons by p2y receptors: a role for ATP and ADP in motor pattern generation

PubMed Central

Brown, Paul; Dale, Nicholas

2002-01-01

We have investigated the pharmacological properties and targets of p2y purinoceptors in Xenopus embryo spinal neurons. ATP reversibly inhibited the voltage-gated K+ currents by 10 ± 3 %. UTP and the analogues α,β-methylene-ATP and 2-methylthio-ATP also inhibited K+ currents. This agonist profile is similar to that reported for a p2y receptor cloned from Xenopus embryos. Voltage-gated K+ currents could be inhibited by ADP (9 ± 0.8 %) suggesting that a further p2y1-like receptor is also present in the embryo spinal cord. Unexpectedly we found that α,β-methylene-ADP, often used to block the ecto-5′-nucleotidase, also inhibited voltage-gated K+ currents (7 ± 2.3 %). This inhibition was occluded by ADP, suggesting that α,β-methylene-ADP is an agonist at p2y1 receptors. We have directly studied the properties of the ecto-5′-nucleotidase in Xenopus embryo spinal cord. Although ADP inhibited this enzyme, α,β-methylene-ADP had no action. Caution therefore needs to be used when interpreting the actions of α,β-methylene-ADP as it has previously unreported agonist activity at P2 receptors. Xenopus spinal neurons possess fast and slow voltage-gated K+ currents. By using catechol to selectively block the fast current, we completely occluded the actions of ATP and ADP. Furthermore, the purines appeared to block only the fast relaxation component of the tail currents. We therefore conclude that the p2y receptors target only the fast component of the delayed rectifier. As ATP breakdown to ADP is rapid and ADP may accumulate at higher levels than ATP, the contribution of ADP acting through p2y1-like receptors may be an important additional mechanism for the control of spinal motor pattern generation. PMID:11986373

75 FR 10328 - Wolf Creek Nuclear Operating Corporation, Wolf Creek Generating Station; Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-05

... Plan, Safeguards Contingency Plan, and Cyber Security Plan referred to collectively hereafter as... its security plans. Pursuant to 10 CFR 51.32, ``Finding of no significant impact,'' the Commission has... by designing and implementing comprehensive site security programs. The amendments to 10 CFR 73.55...

Clostridial ADP-ribosylating toxins: effects on ATP and GTP-binding proteins.

PubMed

Aktories, K

1994-09-01

The actin cytoskeleton appears to be as the cellular target of various clostridial ADP-ribosyltransferases which have been described during recent years. Clostridium botulinum C2 toxin, Clostridium perfringens iota toxin and Clostridium spiroforme toxin ADP-ribosylate actin monomers and inhibit actin polymerization. Clostridium botulinum exoenzyme C3 and Clostridium limosum exoenzyme ADP-ribosylate the low-molecular-mass GTP-binding proteins of the Rho family, which participate in the regulation of the actin cytoskeleton. ADP-ribosylation inactivates the regulatory Rho proteins and disturbs the organization of the actin cytoskeleton.

6 CFR 37.41 - Security plan.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 6 Domestic Security 1 2012-01-01 2012-01-01 false Security plan. 37.41 Section 37.41 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY REAL ID DRIVER'S LICENSES AND IDENTIFICATION CARDS Security at DMVs and Driver's License and Identification Card Production Facilities § 37.41...

6 CFR 37.41 - Security plan.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 6 Domestic Security 1 2011-01-01 2011-01-01 false Security plan. 37.41 Section 37.41 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY REAL ID DRIVER'S LICENSES AND IDENTIFICATION CARDS Security at DMVs and Driver's License and Identification Card Production Facilities § 37.41...

49 CFR 1542.301 - Contingency plan.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Contingency Measures § 1542.301 Contingency plan. (a) Each airport operator required to have a security program under § 1542.103(a) and (b...

49 CFR 1542.301 - Contingency plan.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Contingency Measures § 1542.301 Contingency plan. (a) Each airport operator required to have a security program under § 1542.103(a) and (b...

49 CFR 1542.301 - Contingency plan.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Contingency Measures § 1542.301 Contingency plan. (a) Each airport operator required to have a security program under § 1542.103(a) and (b...

49 CFR 1542.301 - Contingency plan.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Contingency Measures § 1542.301 Contingency plan. (a) Each airport operator required to have a security program under § 1542.103(a) and (b...

Mitochondrial Free [Ca2+] Increases during ATP/ADP Antiport and ADP Phosphorylation: Exploration of Mechanisms

PubMed Central

Haumann, Johan; Dash, Ranjan K.; Stowe, David F.; Boelens, Age D.; Beard, Daniel A.; Camara, Amadou K.S.

2010-01-01

ADP influx and ADP phosphorylation may alter mitochondrial free [Ca2+] ([Ca2+]m) and consequently mitochondrial bioenergetics by several postulated mechanisms. We tested how [Ca2+]m is affected by H2PO4− (Pi), Mg2+, calcium uniporter activity, matrix volume changes, and the bioenergetic state. We measured [Ca2+]m, membrane potential, redox state, matrix volume, pHm, and O2 consumption in guinea pig heart mitochondria with or without ruthenium red, carboxyatractyloside, or oligomycin, and at several levels of Mg2+ and Pi. Energized mitochondria showed a dose-dependent increase in [Ca2+]m after adding CaCl2 equivalent to 20, 114, and 485 nM extramatrix free [Ca2+] ([Ca2+]e); this uptake was attenuated at higher buffer Mg2+. Adding ADP transiently increased [Ca2+]m up to twofold. The ADP effect on increasing [Ca2+]m could be partially attributed to matrix contraction, but was little affected by ruthenium red or changes in Mg2+ or Pi. Oligomycin largely reduced the increase in [Ca2+]m by ADP compared to control, and [Ca2+]m did not return to baseline. Carboxyatractyloside prevented the ADP-induced [Ca2+]m increase. Adding CaCl2 had no effect on bioenergetics, except for a small increase in state 2 and state 4 respiration at 485 nM [Ca2+]e. These data suggest that matrix ADP influx and subsequent phosphorylation increase [Ca2+]m largely due to the interaction of matrix Ca2+ with ATP, ADP, Pi, and cation buffering proteins in the matrix. PMID:20712982

Uridylylation of Herbaspirillum seropedicae GlnB and GlnK proteins is differentially affected by ATP, ADP and 2-oxoglutarate in vitro.

PubMed

Bonatto, Ana C; Souza, Emanuel M; Oliveira, Marco A S; Monteiro, Rose A; Chubatsu, Leda S; Huergo, Luciano F; Pedrosa, Fábio O

2012-08-01

PII are signal-transducing proteins that integrate metabolic signals and transmit this information to a large number of proteins. In proteobacteria, PII are modified by GlnD (uridylyltransferase/uridylyl-removing enzyme) in response to the nitrogen status. The uridylylation/deuridylylation cycle of PII is also regulated by carbon and energy signals such as ATP, ADP and 2-oxoglutarate (2-OG). These molecules bind to PII proteins and alter their tridimensional structure/conformation and activity. In this work, we determined the effects of ATP, ADP and 2-OG levels on the in vitro uridylylation of Herbaspirillum seropedicae PII proteins, GlnB and GlnK. Both proteins were uridylylated by GlnD in the presence of ATP or ADP, although the uridylylation levels were higher in the presence of ATP and under high 2-OG levels. Under excess of 2-OG, the GlnB uridylylation level was higher in the presence of ATP than with ADP, while GlnK uridylylation was similar with ATP or ADP. Moreover, in the presence of ADP/ATP molar ratios varying from 10/1 to 1/10, GlnB uridylylation level decreased as ADP concentration increased, whereas GlnK uridylylation remained constant. The results suggest that uridylylation of both GlnB and GlnK responds to 2-OG levels, but only GlnB responds effectively to variation on ADP/ATP ratio.

Simultaneous determination of aditoprim and its three major metabolites in pigs, broilers and carp tissues, and its application in tissue distribution and depletion studies.

PubMed

Wang, Liye; Huang, Lingli; Pan, Yuanhu; Wu, Qinghua; Xie, Shuyu; Yuan, Zonghui

2016-08-01

Aditoprim (ADP) is a recently developed dihydrofolate reductase inhibitor that has shown promise for therapeutic use in veterinary medicine because of its excellent pharmacokinetic properties. In this study, a sensitive and reliable multi-residue chromatography-ultraviolet (HPLC-UV) method for the quantitative analysis of ADP and its three major metabolites was developed, and the tissue distribution and depletion profiles of ADP and its major metabolites in pigs, broilers and carp were investigated. Edible and additional tissues (heart, lung, stomach, intestine and swim bladder) were collected for analysis at six different withdrawal periods after ADP administration for 7 days. ADP, N-monomethyl-ADP and N-didesmethyl-ADP were detected in almost all tissues in the three species. The liver, kidney and lung showed higher residue concentrations, and the liver showed a longer residue half-life (t1/2) than other tissues. In the liver, ADP was the most abundant component with the longest persistence. The results suggest that the liver was the residual target tissue and ADP was the marker residue, and the conclusive withdrawal time (WDT) of 20 days in pigs, 16 days in broilers and 25 days in carp was estimated using the assessment methodologies approved by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).

A Handbook for Automatic Data Processing Equipment Acquisition.

DTIC Science & Technology

1981-12-01

Navy ADPE Procurement Policies (Automatic Data Processing Equipment (ADPE) procurement by federal agencies is governed by an interlocking network of...ADPE) procurement by federal agencies is governed by an interlocking network of policies and directives issued by federal agencies, the Department...SECNAVINST) and local procedures governing the acquisition of ADPE. Obtaining and understanding this interlocking network of policies is often difficult

Arginine ADP-ribosylation mechanism based on structural snapshots of iota-toxin and actin complex

PubMed Central

Tsurumura, Toshiharu; Tsumori, Yayoi; Qiu, Hao; Oda, Masataka; Sakurai, Jun; Nagahama, Masahiro; Tsuge, Hideaki

2013-01-01

Clostridium perfringens iota-toxin (Ia) mono-ADP ribosylates Arg177 of actin, leading to cytoskeletal disorganization and cell death. To fully understand the reaction mechanism of arginine-specific mono-ADP ribosyl transferase, the structure of the toxin-substrate protein complex must be characterized. Recently, we solved the crystal structure of Ia in complex with actin and the nonhydrolyzable NAD+ analog βTAD (thiazole-4-carboxamide adenine dinucleotide); however, the structures of the NAD+-bound form (NAD+-Ia-actin) and the ADP ribosylated form [Ia-ADP ribosylated (ADPR)-actin] remain unclear. Accidentally, we found that ethylene glycol as cryo-protectant inhibits ADP ribosylation and crystallized the NAD+-Ia-actin complex. Here we report high-resolution structures of NAD+-Ia-actin and Ia-ADPR-actin obtained by soaking apo-Ia-actin crystal with NAD+ under different conditions. The structures of NAD+-Ia-actin and Ia-ADPR-actin represent the pre- and postreaction states, respectively. By assigning the βTAD-Ia-actin structure to the transition state, the strain-alleviation model of ADP ribosylation, which we proposed previously, is experimentally confirmed and improved. Moreover, this reaction mechanism appears to be applicable not only to Ia but also to other ADP ribosyltransferases. PMID:23382240

Overexpression of the ADP (E3-11.6K) protein increases cell lysis and spread of adenovirus.

PubMed

Doronin, Konstantin; Toth, Karoly; Kuppuswamy, Mohan; Krajcsi, Peter; Tollefson, Ann E; Wold, William S M

2003-01-20

Adenoviruses replicate in the nucleus and induce lytic cell death. We have shown previously that efficient cell lysis and release of adenovirus from infected cells requires an 11.6-kDa protein named Adenovirus Death Protein (ADP). The adp gene is located in the early E3 transcription unit, but the gene is expressed primarily at very late stages of infection. The putative function of ADP was discerned previously from the use of virus mutants that lack functional ADP. Here we describe two adenovirus mutants, named VRX-006 and VRX-007, that overexpress ADP. VRX-006 lacks all other genes in the E3 region, and VRX-007 lacks all other E3 genes except 12.5K. VRX-006 and VRX-007 display the phenotype predicted by the proposed function for ADP: they produce early cytopathic effect, early cell lysis, large plaques, and increased cell-to-cell spread. They grow as well in cultured cells as does adenovirus type 5. These results are consistent with the conclusion that ADP functions in adenovirus infections to promote virus release from cells at the culmination of infection.

75 FR 63867 - DTE Energy; Enrico Fermi Atomic Power Plant Unit 1, Exemption From Certain Security Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-18

... procedures, physical security plan, guard training and qualification plan, or cyber security plan for the... Power Plant Unit 1, Exemption From Certain Security Requirements 1.0 Background DTE Energy (DTE) is the... atmospheric pressure. In November 1972, the Power Reactor Development Company (PRDC), the licensee at that...

17 CFR 247.776 - Exemption from the definition of “broker” for banks effecting certain excepted or exempted...

Code of Federal Regulations, 2010 CFR

2010-04-01

... for its employee benefit plans. 247.776 Section 247.776 Commodity and Securities Exchanges SECURITIES... effecting certain excepted or exempted transactions in a company's securities for its employee benefit plans... benefit of an employee benefit plan account; (3) Any such security is obtained directly from: (i) The...

Imaging energy status in live cells with a fluorescent biosensor of the intracellular ATP-to-ADP ratio

PubMed Central

Tantama, Mathew; Martínez-François, Juan Ramón; Mongeon, Rebecca; Yellen, Gary

2013-01-01

The ATP:ADP ratio is a critical parameter of cellular energy status that regulates many metabolic activities. Here we report an optimized genetically-encoded fluorescent biosensor, PercevalHR, that senses the ATP:ADP ratio. PercevalHR is tuned to the range of intracellular ATP:ADP expected in mammalian cells, and it can be used with one- or two-photon microscopy in live samples. We use PercevalHR to visualize activity-dependent changes in ATP:ADP when neurons are exposed to multiple stimuli, demonstrating that it is a sensitive reporter of physiological changes in energy consumption and production. We also use PercevalHR to visualize intracellular ATP:ADP while simultaneously recording currents from ATP-sensitive potassium (KATP) channels in single cells, showing that PercevalHR enables the study of coordinated variation in ATP:ADP and KATP channel open probability in intact cells. With its ability to monitor changes in cellular energetics within seconds, PercevalHR should be a versatile tool for metabolic research. PMID:24096541

Genetics of psychosis of Alzheimer disease.

PubMed

Shah, Chintan; DeMichele-Sweet, Mary Ann A; Sweet, Robert A

2017-01-01

Psychotic symptoms, comprised of delusions and hallucinations, occur in about half of individuals with Alzheimer disease (AD with psychosis, AD+P). These individuals have greater agitation, aggression, depression, functional impairment, and mortality than individuals without psychosis (AD-P). Although the exact etiopathogenesis of AD+P is unclear, the rapidly developing field of genomics continues to expand our understanding of this disease. Several independent studies have demonstrated familial aggregation and heritability of AD+P. Linkage studies have been suggestive of loci on several chromosomes associated with AD+P. Association studies examining apolipoprotein E gene, the best established genetic risk factor for late-onset AD, did not find any significant association of this gene with AD+P. Other candidate gene studies focusing on monoamine neurotransmitter systems have yielded equivocal results. A genome-wide association study and studies examining copy number variations recently have detected suggestive associations, but have been underpowered. Approaches to increase sizes of AD+P samples for genome wide association studies are discussed. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

ADP-ribosyl cyclases regulate early development of the sea urchin.

PubMed

Ramakrishnan, Latha; Uhlinger, Kevin; Dale, Leslie; Hamdoun, Amro; Patel, Sandip

2016-06-01

ADP-ribosyl cyclases are multifunctional enzymes involved in the metabolism of nucleotide derivatives necessary for Ca 2+ signalling such as cADPR and NAADP. Although Ca 2+ signalling is a critical regulator of early development, little is known of the role of ADP-ribosyl cyclases during embryogenesis. Here we analyze the expression, activity and function of ADP-ribosyl cyclases in the embryo of the sea urchin - a key organism for study of both Ca 2+ signalling and embryonic development. ADP-ribosyl cyclase isoforms (SpARC1-4) showed unique changes in expression during early development. These changes were associated with an increase in the ratio of cADPR:NAADP production. Over-expression of SpARC4 (a preferential cyclase) disrupted gastrulation. Our data highlight the importance of ADP-ribosyl cyclases during embryogenesis.

Time course and strain dependence of ADP release during contraction of permeabilized skeletal muscle fibers.

PubMed

West, Timothy G; Hild, Gabor; Siththanandan, Verl B; Webb, Martin R; Corrie, John E T; Ferenczi, Michael A

2009-04-22

A phosphorylated, single cysteine mutant of nucleoside diphosphate kinase, labeled with N-[2-(iodoacetamido)ethyl]-7-diethylaminocoumarin-3-carboxamide (P approximately NDPK-IDCC), was used as a fluorescence probe for time-resolved measurement of changes in [MgADP] during contraction of single permeabilized rabbit psoas fibers. The dephosphorylation of the phosphorylated protein by MgADP occurs within the lattice environment of permeabilized fibers with a second-order rate constant at 12 degrees C of 10(5) M(-1) s(-1). This dephosphorylation is accompanied by a change in coumarin fluorescence. We report the time course of P approximately NDPK-IDCC dephosphorylation during the period of active isometric force redevelopment after quick release of fiber strain at pCa(2+) of 4.5. After a rapid length decrease of 0.5% was applied to the fiber, the extra NDPK-IDCC produced during force recovery, above the value during the approximately steady state of isometric contraction, was 2.7 +/- 0.6 microM and 4.7 +/- 1.5 microM at 12 and 20 degrees C, respectively. The rates of P approximately NDPK-IDCC dephosphorylation during force recovery were 28 and 50 s(-1) at 12 and 20 degrees C, respectively. The time courses of isometric force and P approximately NDPK-IDCC dephosphorylation were simulated using a seven-state reaction scheme. Relative isometric force was modeled by changes in the occupancy of strongly bound A.M.ADP.P(i) and A.M.ADP states. A strain-sensitive A.M.ADP isomerization step was rate-limiting (3-6 s(-1)) in the cross-bridge turnover during isometric contraction. At 12 degrees C, the A.M.ADP.P(i) and the pre- and postisomerization A.M.ADP states comprised 56%, 38%, and 7% of the isometric force-bearing AM states, respectively. At 20 degrees C, the force-bearing A.M.ADP.P(i) state was a lower proportion of the total force-bearing states (37%), whereas the proportion of postisomerization A.M.ADP states was higher (19%). The simulations suggested that release of cross-bridge strain caused rapid depopulation of the preisomerization A.M.ADP state and transient accumulation of MgADP in the postisomerization A.M.ADP state. Hence, the strain-sensitive isomerization of A.M.ADP seems to explain the rate of change of P approximately NDPK-IDCC dephosphorylation during force recovery. The temperature-dependent isometric distribution of myosin states is consistent with the previous observation of a small decrease in amplitude of the P(i) transient during force recovery at 20 degrees C and the current observation of an increase in amplitude of the ADP-sensitive NDPK-IDCC transient.

5 CFR 930.301 - Information systems security awareness training program.

Code of Federal Regulations, 2011 CFR

2011-01-01

... training in system/application life cycle management, risk management, and contingency planning. (4) Chief... security management, system/application life cycle management, risk management, and contingency planning..., risk management, and contingency planning. (b) Provide the Federal information systems security...

5 CFR 930.301 - Information systems security awareness training program.

Code of Federal Regulations, 2010 CFR

2010-01-01

... training in system/application life cycle management, risk management, and contingency planning. (4) Chief... security management, system/application life cycle management, risk management, and contingency planning..., risk management, and contingency planning. (b) Provide the Federal information systems security...

Metabolism Dealing with Thermal Degradation of NAD+ in the Hyperthermophilic Archaeon Thermococcus kodakarensis.

PubMed

Hachisuka, Shin-Ichi; Sato, Takaaki; Atomi, Haruyuki

2017-10-01

NAD + is an important cofactor for enzymatic oxidation reactions in all living organisms, including (hyper)thermophiles. However, NAD + is susceptible to thermal degradation at high temperatures. It can thus be expected that (hyper)thermophiles harbor mechanisms that maintain in vivo NAD + concentrations and possibly remove and/or reuse undesirable degradation products of NAD + Here we confirmed that at 85°C, thermal degradation of NAD + results mostly in the generation of nicotinamide and ADP-ribose, the latter known to display toxicity by spontaneously linking to proteins. The hyperthermophilic archaeon Thermococcus kodakarensis possesses a putative ADP-ribose pyrophosphatase (ADPR-PPase) encoded by the TK2284 gene. ADPR-PPase hydrolyzes ADP-ribose to ribose 5-phosphate (R5P) and AMP. The purified recombinant TK2284 protein exhibited activity toward ADP-ribose as well as ADP-glucose. Kinetic analyses revealed a much higher catalytic efficiency toward ADP-ribose, suggesting that ADP-ribose was the physiological substrate. To gain insight into the physiological function of TK2284, a TK2284 gene disruption strain was constructed and examined. Incubation of NAD + in the cell extract of the mutant strain at 85°C resulted in higher ADP-ribose accumulation and lower AMP production compared with those in experiments with the host strain cell extract. The mutant strain also exhibited lower cell yield and specific growth rates in a synthetic amino acid medium compared with those of the host strain. The results obtained here suggest that the ADPR-PPase in T. kodakarensis is responsible for the cleavage of ADP-ribose to R5P and AMP, providing a means to utilize the otherwise dead-end product of NAD + breakdown. IMPORTANCE Hyperthermophilic microorganisms living under high temperature conditions should have mechanisms that deal with the degradation of thermolabile molecules. NAD + is an important cofactor for enzymatic oxidation reactions and is susceptible to thermal degradation to ADP-ribose and nicotinamide. Here we show that an ADP-ribose pyrophosphatase homolog from the hyperthermophilic archaeon Thermococcus kodakarensis converts the detrimental ADP-ribose to ribose 5-phosphate and AMP, compounds that can be directed to central carbon metabolism. This physiological role for ADP-ribose pyrophosphatases might be universal in hyperthermophiles, as their homologs are widely distributed among both hyperthermophilic bacteria and archaea. Copyright © 2017 American Society for Microbiology.

6 CFR 27.245 - Review and approval of site security plans.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Review and approval of site security plans. 27.245 Section 27.245 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Chemical Facility Security Program § 27.245 Review and approval of site...

6 CFR 27.245 - Review and approval of site security plans.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 6 Domestic Security 1 2014-01-01 2014-01-01 false Review and approval of site security plans. 27.245 Section 27.245 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Chemical Facility Security Program § 27.245 Review and approval of site...

6 CFR 27.245 - Review and approval of site security plans.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 6 Domestic Security 1 2011-01-01 2011-01-01 false Review and approval of site security plans. 27.245 Section 27.245 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Chemical Facility Security Program § 27.245 Review and approval of site...

6 CFR 27.245 - Review and approval of site security plans.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 6 Domestic Security 1 2012-01-01 2012-01-01 false Review and approval of site security plans. 27.245 Section 27.245 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Chemical Facility Security Program § 27.245 Review and approval of site...

6 CFR 27.245 - Review and approval of site security plans.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 6 Domestic Security 1 2013-01-01 2013-01-01 false Review and approval of site security plans. 27.245 Section 27.245 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Chemical Facility Security Program § 27.245 Review and approval of site...

Distribution of protein poly(ADP-ribosyl)ation systems across all domains of life

PubMed Central

Perina, Dragutin; Mikoč, Andreja; Ahel, Josip; Ćetković, Helena; Žaja, Roko; Ahel, Ivan

2014-01-01

Poly(ADP-ribosyl)ation is a post-translational modification of proteins involved in regulation of many cellular pathways. Poly(ADP-ribose) (PAR) consists of chains of repeating ADP-ribose nucleotide units and is synthesized by the family of enzymes called poly(ADP-ribose) polymerases (PARPs). This modification can be removed by the hydrolytic action of poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribosylhydrolase 3 (ARH3). Hydrolytic activity of macrodomain proteins (MacroD1, MacroD2 and TARG1) is responsible for the removal of terminal ADP-ribose unit and for complete reversion of protein ADP-ribosylation. Poly(ADP-ribosyl)ation is widely utilized in eukaryotes and PARPs are present in representatives from all six major eukaryotic supergroups, with only a small number of eukaryotic species that do not possess PARP genes. The last common ancestor of all eukaryotes possessed at least five types of PARP proteins that include both mono and poly(ADP-ribosyl) transferases. Distribution of PARGs strictly follows the distribution of PARP proteins in eukaryotic species. At least one of the macrodomain proteins that hydrolyse terminal ADP-ribose is also always present. Therefore, we can presume that the last common ancestor of all eukaryotes possessed a fully functional and reversible PAR metabolism and that PAR signalling provided the conditions essential for survival of the ancestral eukaryote in its ancient environment. PARP proteins are far less prevalent in bacteria and were probably gained through horizontal gene transfer. Only eleven bacterial species possess all proteins essential for a functional PAR metabolism, although it is not known whether PAR metabolism is truly functional in bacteria. Several dsDNA viruses also possess PARP homologues, while no PARP proteins have been identified in any archaeal genome. Our analysis of the distribution of enzymes involved in PAR metabolism provides insight into the evolution of these important signalling systems, as well as providing the basis for selection of the appropriate genetic model organisms to study the physiology of the specific human PARP proteins. PMID:24865146

33 CFR 128.300 - What is required to be in a Terminal Security Plan?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false What is required to be in a Terminal Security Plan? 128.300 Section 128.300 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... for Terminal Security § 128.300 What is required to be in a Terminal Security Plan? (a) If your...

33 CFR 128.300 - What is required to be in a Terminal Security Plan?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false What is required to be in a Terminal Security Plan? 128.300 Section 128.300 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... for Terminal Security § 128.300 What is required to be in a Terminal Security Plan? (a) If your...

33 CFR 128.300 - What is required to be in a Terminal Security Plan?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false What is required to be in a Terminal Security Plan? 128.300 Section 128.300 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... for Terminal Security § 128.300 What is required to be in a Terminal Security Plan? (a) If your...

17 CFR 230.416 - Securities to be issued as a result of stock splits, stock dividends and anti-dilution provisions...

Code of Federal Regulations, 2010 CFR

2010-04-01

... to certain employee benefit plans. 230.416 Section 230.416 Commodity and Securities Exchanges... provisions and interests to be issued pursuant to certain employee benefit plans. (a) If a registration... pursuant to an employee benefit plan, including interests in such plan that constitute separate securities...

Discrete-Time Local Value Iteration Adaptive Dynamic Programming: Admissibility and Termination Analysis.

PubMed

Wei, Qinglai; Liu, Derong; Lin, Qiao

In this paper, a novel local value iteration adaptive dynamic programming (ADP) algorithm is developed to solve infinite horizon optimal control problems for discrete-time nonlinear systems. The focuses of this paper are to study admissibility properties and the termination criteria of discrete-time local value iteration ADP algorithms. In the discrete-time local value iteration ADP algorithm, the iterative value functions and the iterative control laws are both updated in a given subset of the state space in each iteration, instead of the whole state space. For the first time, admissibility properties of iterative control laws are analyzed for the local value iteration ADP algorithm. New termination criteria are established, which terminate the iterative local ADP algorithm with an admissible approximate optimal control law. Finally, simulation results are given to illustrate the performance of the developed algorithm.In this paper, a novel local value iteration adaptive dynamic programming (ADP) algorithm is developed to solve infinite horizon optimal control problems for discrete-time nonlinear systems. The focuses of this paper are to study admissibility properties and the termination criteria of discrete-time local value iteration ADP algorithms. In the discrete-time local value iteration ADP algorithm, the iterative value functions and the iterative control laws are both updated in a given subset of the state space in each iteration, instead of the whole state space. For the first time, admissibility properties of iterative control laws are analyzed for the local value iteration ADP algorithm. New termination criteria are established, which terminate the iterative local ADP algorithm with an admissible approximate optimal control law. Finally, simulation results are given to illustrate the performance of the developed algorithm.

Hda Monomerization by ADP Binding Promotes Replicase Clamp-mediated DnaA-ATP Hydrolysis*S⃞

PubMed Central

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

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

PubMed

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.

76 FR 45645 - 10-Day Notice of Proposed Information Collection: Technology Security/Clearance Plans, Screening...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-29

...: Technology Security/Clearance Plans, Screening Records, and Non-Disclosure Agreements ACTION: Notice of... Information Collection: Technology Security/ Clearance Plans, Screening Records, and Non-Disclosure Agreements...: None. Respondents: Business and Nonprofit Organizations, Foreign Governments. Estimated Number of...

48 CFR 552.239-70 - Information Technology Security Plan and Security Authorization.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Information Technology... Text of Provisions and Clauses 552.239-70 Information Technology Security Plan and Security Authorization. As prescribed in 539.7002(a), insert the following provision: Information Technology Security...

48 CFR 552.239-70 - Information Technology Security Plan and Security Authorization.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Information Technology... Text of Provisions and Clauses 552.239-70 Information Technology Security Plan and Security Authorization. As prescribed in 539.7002(a), insert the following provision: Information Technology Security...

48 CFR 552.239-70 - Information Technology Security Plan and Security Authorization.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Information Technology... Text of Provisions and Clauses 552.239-70 Information Technology Security Plan and Security Authorization. As prescribed in 539.7002(a), insert the following provision: Information Technology Security...

48 CFR 552.239-70 - Information Technology Security Plan and Security Authorization.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Information Technology... Text of Provisions and Clauses 552.239-70 Information Technology Security Plan and Security Authorization. As prescribed in 539.7002(a), insert the following provision: Information Technology Security...

Calcium modulates the ATP and ADP hydrolysis in human placental mitochondria.

PubMed

Martínez, Federico; Uribe, Aida; Espinosa-García, M Teresa; Flores-Herrera, Oscar; García-Pérez, Cecilia; Milán, Rebeca

2002-08-01

This study evaluated the effect of Ca2+ on the extramitochondrial hydrolysis of ATP and ADP by the extramitochondrial ATPase in isolated mitochondria and submitochondrial particles (SMPs) from human term placenta. The effect of different oxidizable substrates on the hydrolysis of ATP and ADP in the presence of sucrose or K+ was evaluated. Ca2+ increased phosphate release from ATP and ADP, but this stimulation showed different behavior depending on the oxidizable substrate present in the incubation media. Ca2+ stimulated the hydrolysis of ATP and ADP in the presence of sucrose. However, Ca2+ did not stimulate the hydrolysis of ADP in the medium containing K+. Ca2+ showed inhibition depending on the respiratory substrate. This study suggests that the energetic state of mitochondria controls the extramitochondrial ATPase activity, which is modulated by Ca2+ and respiratory substrates.

Intratumoral delivery of docetaxel enhances antitumor activity of Ad-p53 in murine head and neck cancer xenograft model.

PubMed

Yoo, George H; Subramanian, Geetha; Ezzat, Waleed H; Tulunay, Ozlem E; Tran, Vivian R; Lonardo, Fulvio; Ensley, John F; Kim, Harold; Won, Joshua; Stevens, Timothy; Zumstein, Louis A; Lin, Ho-Sheng

2010-01-01

The aim of this study is to determine the ability of intratumorally delivered docetaxel to enhance the antitumor activity of adenovirus-mediated delivery of p53 (Ad-p53) in murine head and neck cancer xenograft model. A xenograft head and neck squamous cell carcinoma mouse model was used. Mice were randomized into 4 groups of 6 mice receiving 6 weeks of biweekly intratumoral injection of (a) diluent, (b) Ad-p53 (1 x 10(10) viral particles per injection), (c) docetaxel (1 mg/kg per injection), and (d) combination of Ad-p53 (1 x 10(10) viral particles per injection) and docetaxel (1 mg/kg per injection). Tumor size, weight, toxicity, and overall and disease-free survival rates were determined. Intratumoral treatments with either docetaxel alone or Ad-p53 alone resulted in statistically significant antitumor activity and improved survival compared with control group. Furthermore, combined delivery of Ad-p53 and docetaxel resulted in a statistically significant reduction in tumor weight when compared to treatment with either Ad-p53 or docetaxel alone. Intratumoral delivery of docetaxel enhanced the antitumor effect of Ad-p53 in murine head and neck cancer xenograft model. The result of this preclinical in vivo study is promising and supports further clinical testing to evaluate efficacy of combined intratumoral docetaxel and Ad-p53 in treatment of head and neck cancer. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Characterization of the aggregation responses of camel platelets.

PubMed

Al Ghumlas, Abeer K; Gader, Abdel Galil M Abdel

2013-09-01

Despite evidence of active hemostasis, camel platelets barely respond to common aggregating agents at standard doses used for human platelet aggregation. The purpose of the study was to find out whether camel platelets can be activated by high doses or combinations of aggregation agonists, and to characterize the receptor that mediates the aggregation response to adenosine diphosphate (ADP), the most potent agonist for camel platelets known so far. Aggregation studies were performed with platelet-rich plasma (PRP) in response to multiple doses or combinations of ADP, epinephrine (EPN), collagen, and arachidonic acid (AA). Aggregation responses to ADP were performed before and after the addition of the ADP receptor (P2Y12) antagonist Clopidogrel. Camel platelets responded to ADP at doses higher than the standard dose for human platelets, and to combinations of EPN and other agonists, while no aggregation was elicited with EPN or AA alone. Clopidogrel blocked the ADP-induced aggregation responses in a dose-dependent fashion in vitro. Camel platelet aggregation can be activated by increasing the dose of some agonists such as ADP, but not AA or EPN. Irreversible aggregation of camel platelets could also be triggered by a combination of EPN and ADP, and collagen and AA. Inhibition with clopidogrel suggests that camel platelets express the ADP receptor, P2Y12. Understanding platelet function in camels will add to the understanding of platelet function in health and disease. © 2013 American Society for Veterinary Clinical Pathology.

Poly(ADP-ribose) polymerases covalently modify strand break termini in DNA fragments in vitro

PubMed Central

Talhaoui, Ibtissam; Lebedeva, Natalia A.; Zarkovic, Gabriella; Saint-Pierre, Christine; Kutuzov, Mikhail M.; Sukhanova, Maria V.; Matkarimov, Bakhyt T.; Gasparutto, Didier; Saparbaev, Murat K.; Lavrik, Olga I.; Ishchenko, Alexander A.

2016-01-01

Poly(ADP-ribose) polymerases (PARPs/ARTDs) use nicotinamide adenine dinucleotide (NAD+) to catalyse the synthesis of a long branched poly(ADP-ribose) polymer (PAR) attached to the acceptor amino acid residues of nuclear proteins. PARPs act on single- and double-stranded DNA breaks by recruiting DNA repair factors. Here, in in vitro biochemical experiments, we found that the mammalian PARP1 and PARP2 proteins can directly ADP-ribosylate the termini of DNA oligonucleotides. PARP1 preferentially catalysed covalent attachment of ADP-ribose units to the ends of recessed DNA duplexes containing 3′-cordycepin, 5′- and 3′-phosphate and also to 5′-phosphate of a single-stranded oligonucleotide. PARP2 preferentially ADP-ribosylated the nicked/gapped DNA duplexes containing 5′-phosphate at the double-stranded termini. PAR glycohydrolase (PARG) restored native DNA structure by hydrolysing PAR-DNA adducts generated by PARP1 and PARP2. Biochemical and mass spectrometry analyses of the adducts suggested that PARPs utilise DNA termini as an alternative to 2′-hydroxyl of ADP-ribose and protein acceptor residues to catalyse PAR chain initiation either via the 2′,1″-O-glycosidic ribose-ribose bond or via phosphodiester bond formation between C1′ of ADP-ribose and the phosphate of a terminal deoxyribonucleotide. This new type of post-replicative modification of DNA provides novel insights into the molecular mechanisms underlying biological phenomena of ADP-ribosylation mediated by PARPs. PMID:27471034

Is adiponectin a marker of preclinical atherosclerosis in kidney transplantation?

PubMed

Cañas, Laura; Bayés, Beatriz; Granada, Maria L; Ibernon, Meritxell; Porrini, Esteban; Benítez, Rosa; Díaz, Juan M; Lauzurica, Ricardo; Moreso, Francesc; Torres, Armando; Lampreabe, Ildefonso; Serra, Assumpta; Romero, Ramon

2012-01-01

The aim of this study was to analyze the relationship between pre-transplant adiponectin (pre-ADP), abnormalities in glucose homeostasis (AGH) at three months post-transplantation, and preclinical atherosclerosis in non-diabetic patients prior to kidney transplantation (KT). We carried out a multicenter study in 157 non-diabetic KT patients (66.5% men; age: 50±13 yr). Pre-ADP levels were analyzed using radioimmunoassay. Carotid ultrasound was performed to determine carotid intima-media thickness (c-IMT). Oral glucose tolerance test was carried out to classify patients according ADA criteria. Of the patients, 52.8% had AGH. Median pre-ADP was 19.5 (14-27) μg/mL. An inverse correlation was found between ADP and HOMA index (r=-0.432; p<0.001). Median c-IMT was 0.6 (0.48-0.71) mm. Significant inverse correlation existed between ADP and c-IMT on both sides (p<0.05). Patients with c-IMT >0.6 mm had more AGH (p=0.012) and lower ADP levels (p=0.02). We performed a logistic regression analysis using preclinical atherosclerosis (c-IMT ≥0.6 mm) as dependent variable and sex, age, BMI, ADP, AGH, and HOMA index as independent variables of altered c-IMT. Age, pre-ADP, and AGH were independent risk factors for elevated c-IMT. Patients with AGH have a greater presence of preclinical atherosclerosis. ADP has an inverse relationship with AGH and is an independent marker of preclinical atherosclerosis. © 2011 John Wiley & Sons A/S.

49 CFR 1544.301 - Contingency plan.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRCRAFT OPERATOR SECURITY: AIR CARRIERS AND... notified of any changes. (c) Participate in an airport-sponsored exercise of the airport contingency plan...

49 CFR 1544.301 - Contingency plan.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRCRAFT OPERATOR SECURITY: AIR CARRIERS AND... notified of any changes. (c) Participate in an airport-sponsored exercise of the airport contingency plan...

49 CFR 1544.301 - Contingency plan.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRCRAFT OPERATOR SECURITY: AIR CARRIERS AND... notified of any changes. (c) Participate in an airport-sponsored exercise of the airport contingency plan...

49 CFR 1544.301 - Contingency plan.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRCRAFT OPERATOR SECURITY: AIR CARRIERS AND... notified of any changes. (c) Participate in an airport-sponsored exercise of the airport contingency plan...

Mechanisms of the cytopathic action of actin-ADP-ribosylating toxins.

PubMed

Aktories, K; Wegner, A

1992-10-01

Clostridium botulinum C2 toxin, Clostridium perfringens iota toxin, and Clostridium spiroforme toxin ADP-ribosylate actin monomers. Toxin-induced ADP-ribosylation disturbs the cellular equilibrium between monomeric and polymeric actin and traps monomeric actin in its unpolymerized form, thereby depolymerizing actin filaments and destroying the microfilament network. Furthermore, the toxins ADP-ribosylate gelsolin actin complexes. These modifications may contribute to the cytopathic action of the toxins.

Production by Clostridium spiroforme of an iotalike toxin that possesses mono(ADP-ribosyl)transferase activity: identification of a novel class of ADP-ribosyltransferases.

PubMed

Simpson, L L; Stiles, B G; Zepeda, H; Wilkins, T D

1989-01-01

Clostridium spiroforme iotalike toxin produced time- and concentration-dependent incorporation of ADP-ribose into homo-poly-L-arginine. Polyasparagine, polyglutamic acid, polylysine, and agmatine were poor substrates. Enzyme activity was associated with the light-chain polypeptide of the toxin. The heavy chain did not possess ADP-ribosyltransferase activity, nor did it enhance or inhibit activity of the light chain. In broken-cell assays, the toxin acted mainly on G-actin, rather than F-actin. A single ADP-ribose group was transferred to each substrate molecule (G-actin). The enzyme was heat sensitive, had a pH optimum in the range of 7 to 8, was inhibited by high concentrations of nicotinamide, and was reversibly denatured by urea and guanidine. Physiological levels of nucleotides (AMP, ADP, ATP, and ADP-ribose) and cations (Na+, K+, Ca2+, and Mg2+) were not very active as enzyme inhibitors. The toxin was structurally and functionally similar to Clostridium botulinum type C2 toxin and Clostridium perfringens iota toxin. When combined with previous findings, the data suggest that a new class of mono(ADP-ribosyl)ating toxins has been found and that these agents belong to a related and possibly homologous series of binary toxins.

Production by Clostridium spiroforme of an iotalike toxin that possesses mono(ADP-ribosyl)transferase activity: identification of a novel class of ADP-ribosyltransferases.

PubMed Central

Simpson, L L; Stiles, B G; Zepeda, H; Wilkins, T D

1989-01-01

Clostridium spiroforme iotalike toxin produced time- and concentration-dependent incorporation of ADP-ribose into homo-poly-L-arginine. Polyasparagine, polyglutamic acid, polylysine, and agmatine were poor substrates. Enzyme activity was associated with the light-chain polypeptide of the toxin. The heavy chain did not possess ADP-ribosyltransferase activity, nor did it enhance or inhibit activity of the light chain. In broken-cell assays, the toxin acted mainly on G-actin, rather than F-actin. A single ADP-ribose group was transferred to each substrate molecule (G-actin). The enzyme was heat sensitive, had a pH optimum in the range of 7 to 8, was inhibited by high concentrations of nicotinamide, and was reversibly denatured by urea and guanidine. Physiological levels of nucleotides (AMP, ADP, ATP, and ADP-ribose) and cations (Na+, K+, Ca2+, and Mg2+) were not very active as enzyme inhibitors. The toxin was structurally and functionally similar to Clostridium botulinum type C2 toxin and Clostridium perfringens iota toxin. When combined with previous findings, the data suggest that a new class of mono(ADP-ribosyl)ating toxins has been found and that these agents belong to a related and possibly homologous series of binary toxins. Images PMID:2521214

50 CFR 37.14 - Bonding.

Code of Federal Regulations, 2012 CFR

2012-10-01

... WILDLIFE REFUGE SYSTEM GEOLOGICAL AND GEOPHYSICAL EXPLORATION OF THE COASTAL PLAIN, ARCTIC NATIONAL... a surety bond of not less than $100,000, or other security satisfactory to the Service, to secure... needed to secure performance of its exploration plan and plan(s) of operation and compliance with the...

On problems of analyzing aerodynamic properties of blunted rotary bodies with small random surface distortions under supersonic and hypersonic flows

NASA Astrophysics Data System (ADS)

Degtyar, V. G.; Kalashnikov, S. T.; Mokin, Yu. A.

2017-10-01

The paper considers problems of analyzing aerodynamic properties (ADP) of reenetry vehicles (RV) as blunted rotary bodies with small random surface distortions. The interactions of math simulation of surface distortions, selection of tools for predicting ADPs of shaped bodies, evaluation of different-type ADP variations and their adaptation for dynamic problems are analyzed. The possibilities of deterministic and probabilistic approaches to evaluation of ADP variations are considered. The practical value of the probabilistic approach is demonstrated. The examples of extremal deterministic evaluations of ADP variations for a sphere and a sharp cone are given.

ADP Analysis project for the Human Resources Management Division

NASA Technical Reports Server (NTRS)

Tureman, Robert L., Jr.

1993-01-01

The ADP (Automated Data Processing) Analysis Project was conducted for the Human Resources Management Division (HRMD) of NASA's Langley Research Center. The three major areas of work in the project were computer support, automated inventory analysis, and an ADP study for the Division. The goal of the computer support work was to determine automation needs of Division personnel and help them solve computing problems. The goal of automated inventory analysis was to find a way to analyze installed software and usage on a Macintosh. Finally, the ADP functional systems study for the Division was designed to assess future HRMD needs concerning ADP organization and activities.

42 CFR 73.11 - Security.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Security. 73.11 Section 73.11 Public Health PUBLIC... AND TOXINS § 73.11 Security. (a) An individual or entity required to register under this part must develop and implement a written security plan. The security plan must be sufficient to safeguard the...

9 CFR 121.11 - Security.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Security. 121.11 Section 121.11... AGENTS AND TOXINS § 121.11 Security. (a) An individual or entity required to register under this part must develop and implement a written security plan. The security plan must be sufficient to safeguard...

9 CFR 121.11 - Security.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Security. 121.11 Section 121.11... AGENTS AND TOXINS § 121.11 Security. (a) An individual or entity required to register under this part must develop and implement a written security plan. The security plan must be sufficient to safeguard...

42 CFR 73.11 - Security.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Security. 73.11 Section 73.11 Public Health PUBLIC... AND TOXINS § 73.11 Security. (a) An individual or entity required to register under this part must develop and implement a written security plan. The security plan must be sufficient to safeguard the...

7 CFR 331.11 - Security.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Security. 331.11 Section 331.11 Agriculture..., DEPARTMENT OF AGRICULTURE POSSESSION, USE, AND TRANSFER OF SELECT AGENTS AND TOXINS § 331.11 Security. Link... register under this part must develop and implement a written security plan. The security plan must be...

42 CFR 73.11 - Security.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Security. 73.11 Section 73.11 Public Health PUBLIC... AND TOXINS § 73.11 Security. (a) An individual or entity required to register under this part must develop and implement a written security plan. The security plan must be sufficient to safeguard the...

42 CFR 73.11 - Security.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Security. 73.11 Section 73.11 Public Health PUBLIC... AND TOXINS § 73.11 Security. (a) An individual or entity required to register under this part must develop and implement a written security plan. The security plan must be sufficient to safeguard the...

9 CFR 121.11 - Security.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Security. 121.11 Section 121.11... AGENTS AND TOXINS § 121.11 Security. (a) An individual or entity required to register under this part must develop and implement a written security plan. The security plan must be sufficient to safeguard...

9 CFR 121.11 - Security.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Security. 121.11 Section 121.11... AGENTS AND TOXINS § 121.11 Security. (a) An individual or entity required to register under this part must develop and implement a written security plan. The security plan must be sufficient to safeguard...

17 CFR 239.16b - Form S-8, for registration under the Securities Act of 1933 of securities to be offered to...

Code of Federal Regulations, 2010 CFR

2010-04-01

... under the Securities Act of 1933 of securities to be offered to employees pursuant to employee benefit... employee benefit plans. (a) Any registrant that, immediately prior to the time of filing a registration... benefit plan. The form also is available for the exercise of employee benefit plan options by an employee...

Functions of the poly(ADP-ribose) polymerase superfamily in plants.

PubMed

Lamb, Rebecca S; Citarelli, Matteo; Teotia, Sachin

2012-01-01

Poly(ADP-ribosyl)ation is the covalent attachment of ADP-ribose subunits from NAD(+) to target proteins and was first described in plants in the 1970s. This post-translational modification is mediated by poly(ADP-ribose) polymerases (PARPs) and removed by poly(ADP-ribose) glycohydrolases (PARGs). PARPs have important functions in many biological processes including DNA repair, epigenetic regulation and transcription. However, these roles are not always associated with enzymatic activity. The PARP superfamily has been well studied in animals, but remains under-investigated in plants. Although plants lack the variety of PARP superfamily members found in mammals, they do encode three different types of PARP superfamily proteins, including a group of PARP-like proteins, the SRO family, that are plant specific. In plants, members of the PARP family and/or poly(ADP-ribosyl)ation have been linked to DNA repair, mitosis, innate immunity and stress responses. In addition, members of the SRO family have been shown to be necessary for normal sporophytic development. In this review, we summarize the current state of plant research into poly(ADP-ribosyl)ation and the PARP superfamily in plants.

Roles of Asp179 and Glu270 in ADP-Ribosylation of Actin by Clostridium perfringens Iota Toxin

PubMed Central

Belyy, Alexander; Tabakova, Irina; Lang, Alexander E.; Jank, Thomas; Belyi, Yury; Aktories, Klaus

2015-01-01

Clostridium perfringens iota toxin is a binary toxin composed of the enzymatically active component Ia and receptor binding component Ib. Ia is an ADP-ribosyltransferase, which modifies Arg177 of actin. The previously determined crystal structure of the actin-Ia complex suggested involvement of Asp179 of actin in the ADP-ribosylation reaction. To gain more insights into the structural requirements of actin to serve as a substrate for toxin-catalyzed ADP-ribosylation, we engineered Saccharomyces cerevisiae strains, in which wild type actin was replaced by actin variants with substitutions in residues located on the Ia-actin interface. Expression of the actin mutant Arg177Lys resulted in complete resistance towards Ia. Actin mutation of Asp179 did not change Ia-induced ADP-ribosylation and growth inhibition of S. cerevisiae. By contrast, substitution of Glu270 of actin inhibited the toxic action of Ia and the ADP-ribosylation of actin. In vitro transcribed/translated human β-actin confirmed the crucial role of Glu270 in ADP-ribosylation of actin by Ia. PMID:26713879

Simulation-based decision support framework for dynamic ambulance redeployment in Singapore.

PubMed

Lam, Sean Shao Wei; Ng, Clarence Boon Liang; Nguyen, Francis Ngoc Hoang Long; Ng, Yih Yng; Ong, Marcus Eng Hock

2017-10-01

Dynamic ambulance redeployment policies tend to introduce much more flexibilities in improving ambulance resource allocation by capitalizing on the definite geospatial-temporal variations in ambulance demand patterns over the time-of-the-day and day-of-the-week effects. A novel modelling framework based on the Approximate Dynamic Programming (ADP) approach leveraging on a Discrete Events Simulation (DES) model for dynamic ambulance redeployment in Singapore is proposed in this paper. The study was based on the Singapore's national Emergency Medical Services (EMS) system. Based on a dataset comprising 216,973 valid incidents over a continuous two-years study period from 1 January 2011-31 December 2012, a DES model for the EMS system was developed. An ADP model based on linear value function approximations was then evaluated using the DES model via the temporal difference (TD) learning family of algorithms. The objective of the ADP model is to derive approximate optimal dynamic redeployment policies based on the primary outcome of ambulance coverage. Considering an 8min response time threshold, an estimated 5% reduction in the proportion of calls that cannot be reached within the threshold (equivalent to approximately 8000 dispatches) was observed from the computational experiments. The study also revealed that the redeployment policies which are restricted within the same operational division could potentially result in a more promising response time performance. Furthermore, the best policy involved the combination of redeploying ambulances whenever they are released from service and that of relocating ambulances that are idle in bases. This study demonstrated the successful application of an approximate modelling framework based on ADP that leverages upon a detailed DES model of the Singapore's EMS system to generate approximate optimal dynamic redeployment plans. Various policies and scenarios relevant to the Singapore EMS system were evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

78 FR 15797 - Service Delivery Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-12

... SOCIAL SECURITY ADMINISTRATION [Docket No. SSA-2012-0048] Service Delivery Plan AGENCY: Social... information, such as Social Security numbers or medical information. 1. Internet: We strongly recommend that... Regulations and Reports Clearance, Social Security Administration, 107 Altmeyer Building, 6401 Security...

Safe teleradiology: information assurance as project planning methodology

NASA Astrophysics Data System (ADS)

Collmann, Jeff R.; Alaoui, Adil; Nguyen, Dan; Lindisch, David

2003-05-01

This project demonstrates use of OCTAVE, an information security risk assessment method, as an approach to the safe design and planning of a teleradiology system. By adopting this approach to project planning, we intended to provide evidence that including information security as an intrinsic component of project planning improves information assurance and that using information assurance as a planning tool produces and improves the general system management plan. Several considerations justify this approach to planning a safe teleradiology system. First, because OCTAVE was designed as a method for retrospectively assessing and proposing enhancements for the security of existing information management systems, it should function well as a guide to prospectively designing and deploying a secure information system such as teleradiology. Second, because OCTAVE provides assessment and planning tools for use primarily by interdisciplinary teams from user organizations, not consultants, it should enhance the ability of such teams at the local level to plan safe information systems. Third, from the perspective of sociological theory, OCTAVE explicitly attempts to enhance organizational conditions identified as necessary to safely manage complex technologies. Approaching information system design from the perspective of information security risk management proactively integrates health information assurance into a project"s core. This contrasts with typical approaches that perceive "security" as a secondary attribute to be "added" after designing the system and with approaches that identify information assurance only with security devices and user training. The perspective of health information assurance embraces so many dimensions of a computerized health information system"s design that one may successfully deploy a method for retrospectively assessing information security risk as a prospective planning tool. From a sociological perspective, this approach enhances the general conditions as well as establishes specific policies and procedures for reliable performance of health information assurance.

48 CFR 1252.239-71 - Information technology security plan and accreditation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Information technology... Provisions and Clauses 1252.239-71 Information technology security plan and accreditation. As prescribed in (TAR) 48 CFR 1239.70, insert the following provision: Information Technology Security Plan and...

48 CFR 1252.239-71 - Information technology security plan and accreditation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Information technology... Provisions and Clauses 1252.239-71 Information technology security plan and accreditation. As prescribed in (TAR) 48 CFR 1239.70, insert the following provision: Information Technology Security Plan and...

48 CFR 1252.239-71 - Information technology security plan and accreditation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Information technology... Provisions and Clauses 1252.239-71 Information technology security plan and accreditation. As prescribed in (TAR) 48 CFR 1239.70, insert the following provision: Information Technology Security Plan and...

48 CFR 1252.239-71 - Information technology security plan and accreditation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Information technology... Provisions and Clauses 1252.239-71 Information technology security plan and accreditation. As prescribed in (TAR) 48 CFR 1239.70, insert the following provision: Information Technology Security Plan and...

48 CFR 1252.239-71 - Information technology security plan and accreditation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Information technology... Provisions and Clauses 1252.239-71 Information technology security plan and accreditation. As prescribed in (TAR) 48 CFR 1239.70, insert the following provision: Information Technology Security Plan and...

ε Subunit of Bacillus subtilis F1-ATPase Relieves MgADP Inhibition

PubMed Central

Mizumoto, Junya; Kikuchi, Yuka; Nakanishi, Yo-Hei; Mouri, Naoto; Cai, Anrong; Ohta, Tokushiro; Haruyama, Takamitsu; Kato-Yamada, Yasuyuki

2013-01-01

MgADP inhibition, which is considered as a part of the regulatory system of ATP synthase, is a well-known process common to all F1-ATPases, a soluble component of ATP synthase. The entrapment of inhibitory MgADP at catalytic sites terminates catalysis. Regulation by the ε subunit is a common mechanism among F1-ATPases from bacteria and plants. The relationship between these two forms of regulatory mechanisms is obscure because it is difficult to distinguish which is active at a particular moment. Here, using F1-ATPase from Bacillus subtilis (BF1), which is strongly affected by MgADP inhibition, we can distinguish MgADP inhibition from regulation by the ε subunit. The ε subunit did not inhibit but activated BF1. We conclude that the ε subunit relieves BF1 from MgADP inhibition. PMID:23967352

Reduced Mutation Rate and Increased Transformability of Transposon-Free Acinetobacter baylyi ADP1-ISx

PubMed Central

Suárez, Gabriel A.; Renda, Brian A.; Dasgupta, Aurko

2017-01-01

ABSTRACT The genomes of most bacteria contain mobile DNA elements that can contribute to undesirable genetic instability in engineered cells. In particular, transposable insertion sequence (IS) elements can rapidly inactivate genes that are important for a designed function. We deleted all six copies of IS1236 from the genome of the naturally transformable bacterium Acinetobacter baylyi ADP1. The natural competence of ADP1 made it possible to rapidly repair deleterious point mutations that arose during strain construction. In the resulting ADP1-ISx strain, the rates of mutations inactivating a reporter gene were reduced by 7- to 21-fold. This reduction was higher than expected from the incidence of new IS1236 insertions found during a 300-day mutation accumulation experiment with wild-type ADP1 that was used to estimate spontaneous mutation rates in the strain. The extra improvement appears to be due in part to eliminating large deletions caused by IS1236 activity, as the point mutation rate was unchanged in ADP1-ISx. Deletion of an error-prone polymerase (dinP) and a DNA damage response regulator (umuDAb [the umuD gene of A. baylyi]) from the ADP1-ISx genome did not further reduce mutation rates. Surprisingly, ADP1-ISx exhibited increased transformability. This improvement may be due to less autolysis and aggregation of the engineered cells than of the wild type. Thus, deleting IS elements from the ADP1 genome led to a greater than expected increase in evolutionary reliability and unexpectedly enhanced other key strain properties, as has been observed for other clean-genome bacterial strains. ADP1-ISx is an improved chassis for metabolic engineering and other applications. IMPORTANCE Acinetobacter baylyi ADP1 has been proposed as a next-generation bacterial host for synthetic biology and genome engineering due to its ability to efficiently take up DNA from its environment during normal growth. We deleted transposable elements that are capable of copying themselves, inserting into other genes, and thereby inactivating them from the ADP1 genome. The resulting “clean-genome” ADP1-ISx strain exhibited larger reductions in the rates of inactivating mutations than expected from spontaneous mutation rates measured via whole-genome sequencing of lineages evolved under relaxed selection. Surprisingly, we also found that IS element activity reduces transformability and is a major cause of cell aggregation and death in wild-type ADP1 grown under normal laboratory conditions. More generally, our results demonstrate that domesticating a bacterial genome by removing mobile DNA elements that have accumulated during evolution in the wild can have unanticipated benefits. PMID:28667117

Reduced Mutation Rate and Increased Transformability of Transposon-Free Acinetobacter baylyi ADP1-ISx.

PubMed

Suárez, Gabriel A; Renda, Brian A; Dasgupta, Aurko; Barrick, Jeffrey E

2017-09-01

The genomes of most bacteria contain mobile DNA elements that can contribute to undesirable genetic instability in engineered cells. In particular, transposable insertion sequence (IS) elements can rapidly inactivate genes that are important for a designed function. We deleted all six copies of IS 1236 from the genome of the naturally transformable bacterium Acinetobacter baylyi ADP1. The natural competence of ADP1 made it possible to rapidly repair deleterious point mutations that arose during strain construction. In the resulting ADP1-ISx strain, the rates of mutations inactivating a reporter gene were reduced by 7- to 21-fold. This reduction was higher than expected from the incidence of new IS 1236 insertions found during a 300-day mutation accumulation experiment with wild-type ADP1 that was used to estimate spontaneous mutation rates in the strain. The extra improvement appears to be due in part to eliminating large deletions caused by IS 1236 activity, as the point mutation rate was unchanged in ADP1-ISx. Deletion of an error-prone polymerase ( dinP ) and a DNA damage response regulator ( umuD Ab [the umuD gene of A. baylyi ]) from the ADP1-ISx genome did not further reduce mutation rates. Surprisingly, ADP1-ISx exhibited increased transformability. This improvement may be due to less autolysis and aggregation of the engineered cells than of the wild type. Thus, deleting IS elements from the ADP1 genome led to a greater than expected increase in evolutionary reliability and unexpectedly enhanced other key strain properties, as has been observed for other clean-genome bacterial strains. ADP1-ISx is an improved chassis for metabolic engineering and other applications. IMPORTANCE Acinetobacter baylyi ADP1 has been proposed as a next-generation bacterial host for synthetic biology and genome engineering due to its ability to efficiently take up DNA from its environment during normal growth. We deleted transposable elements that are capable of copying themselves, inserting into other genes, and thereby inactivating them from the ADP1 genome. The resulting "clean-genome" ADP1-ISx strain exhibited larger reductions in the rates of inactivating mutations than expected from spontaneous mutation rates measured via whole-genome sequencing of lineages evolved under relaxed selection. Surprisingly, we also found that IS element activity reduces transformability and is a major cause of cell aggregation and death in wild-type ADP1 grown under normal laboratory conditions. More generally, our results demonstrate that domesticating a bacterial genome by removing mobile DNA elements that have accumulated during evolution in the wild can have unanticipated benefits. Copyright © 2017 American Society for Microbiology.

[Compliance with guidelines by state plans for food and nutritional security in Brazil].

PubMed

Machado, Mick Lennon; Gabriel, Cristine Garcia; Soar, Claudia; Mamed, Gisele Rockenbach; Machado, Patrícia Maria de Oliveira; Lacerda, Josimari Telino de; Martins, Milena Corrêa; Marcon, Maria Cristina

2018-02-05

A descriptive and documental study was performed from August to October 2016 to analyze compliance by state plans for food and nutritional security (PlanSAN) with the guidelines set by the Brazilian National Policy for Food and Nutritional Security (PNSAN). The state plans were accessed via the websites of the Inter-Ministerial Chamber for Food and Nutritional Security (CAISAN) or the state governments, plus complementary data collection at the state level. All the states of Brazil joined the National System for Food and Nutritional Security (SISAN), while fewer than half (13 states, 48%) had drafted their plans. Of these, 5 (38%) of the PlanSAN had schedules that coincided with the same state's pluriannual plan, 5 (38%) of the PlanSAN specified the budget requirements for meeting the proposed targets, 7 (54%) specified mechanisms for monitoring the plan, and only 2 (15%) defined methodologies for monitoring food and nutritional security. The recent existence of (and adherence to) the CAISAN appear to be related to the lack of state plans in half the states. Although most of the states that did have plans met some of the guidelines laid out by the PNSAN, these mechanisms become weak and impractical when they lack earmarked budget funds to meet their targets. Since the PNSAN is structurally inter-sectorial, the development of plans requires collective work by various government departments. Importantly, the items analyzed here are all guidelines, which implies the need for mechanisms to monitor their actual implementation.

49 CFR 172.802 - Components of a security plan.

Code of Federal Regulations, 2010 CFR

2010-10-01

... from origin to destination, including shipments stored incidental to movement. (b) The security plan must also include the following: (1) Identification by job title of the senior management official... business and must make the security plan available upon request, at a reasonable time and location, to an...

48 CFR 652.239-70 - Information Technology Security Plan and Accreditation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Information Technology... Clauses 652.239-70 Information Technology Security Plan and Accreditation. As prescribed in 639.107-70(a), insert the following provision: Information Technology Security Plan and Accreditation (SEP 2007) All...

48 CFR 652.239-70 - Information Technology Security Plan and Accreditation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Information Technology... Clauses 652.239-70 Information Technology Security Plan and Accreditation. As prescribed in 639.107-70(a), insert the following provision: Information Technology Security Plan and Accreditation (SEP 2007) All...

48 CFR 652.239-70 - Information Technology Security Plan and Accreditation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Information Technology... Clauses 652.239-70 Information Technology Security Plan and Accreditation. As prescribed in 639.107-70(a), insert the following provision: Information Technology Security Plan and Accreditation (SEP 2007) All...

48 CFR 652.239-70 - Information Technology Security Plan and Accreditation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Information Technology... Clauses 652.239-70 Information Technology Security Plan and Accreditation. As prescribed in 639.107-70(a), insert the following provision: Information Technology Security Plan and Accreditation (SEP 2007) All...

41 CFR 102-192.80 - How do we develop written security policies and plans?

Code of Federal Regulations, 2014 CFR

2014-01-01

... service and/or the Federal Protective Service to develop agency mail security policies and plans. The... written security policies and plans? 102-192.80 Section 102-192.80 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION...

41 CFR 102-192.80 - How do we develop written security policies and plans?

Code of Federal Regulations, 2013 CFR

2013-07-01

... service and/or the Federal Protective Service to develop agency mail security policies and plans. The... written security policies and plans? 102-192.80 Section 102-192.80 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION...

41 CFR 102-192.80 - How do we develop written security policies and plans?

Code of Federal Regulations, 2012 CFR

2012-01-01

... service and/or the Federal Protective Service to develop agency mail security policies and plans. The... written security policies and plans? 102-192.80 Section 102-192.80 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION...

41 CFR 102-192.80 - How do we develop written security policies and plans?

Code of Federal Regulations, 2011 CFR

2011-01-01

... service and/or the Federal Protective Service to develop agency mail security policies and plans. The... written security policies and plans? 102-192.80 Section 102-192.80 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION...

77 FR 55864 - Applications and Amendments to Facility Operating Licenses and Combined Licenses Involving...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

.... ML111940200), which approved the RBS Cyber Security Plan and associated implementation milestone schedule. The Cyber Security Plan Implementation Schedule contained in the licensee's letter dated April 4, 2011... consequences of an accident previously evaluated? Response: No. The proposed change to the Cyber Security Plan...

48 CFR 652.239-70 - Information Technology Security Plan and Accreditation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Information Technology... Clauses 652.239-70 Information Technology Security Plan and Accreditation. As prescribed in 639.107-70(a), insert the following provision: Information Technology Security Plan and Accreditation (SEP 2007) All...

Ectopic adenine nucleotide translocase activity controls extracellular ADP levels and regulates the F1-ATPase-mediated HDL endocytosis pathway on hepatocytes.

PubMed

Cardouat, G; Duparc, T; Fried, S; Perret, B; Najib, S; Martinez, L O

2017-09-01

Ecto-F 1 -ATPase is a complex related to mitochondrial ATP synthase which has been identified as a plasma membrane receptor for apolipoprotein A-I (apoA-I), the major protein of high-density lipoprotein (HDL), and has been shown to contribute to HDL endocytosis in several cell types. On hepatocytes, apoA-I binding to ecto-F 1 -ATPase stimulates extracellular ATP hydrolysis into ADP, which subsequently activates a P2Y 13 -mediated HDL endocytosis pathway. Interestingly, other mitochondrial proteins have been found to be expressed at the plasma membrane of several cell types. Among these, adenine nucleotide translocase (ANT) is an ADP/ATP carrier but its role in controlling extracellular ADP levels and F 1 -ATPase-mediated HDL endocytosis has never been investigated. Here we confirmed the presence of ANT at the plasma membrane of human hepatocytes. We then showed that ecto-ANT activity increases or reduces extracellular ADP level, depending on the extracellular ADP/ATP ratio. Interestingly, ecto-ANT co-localized with ecto-F 1 -ATPase at the hepatocyte plasma membrane and pharmacological inhibition of ecto-ANT activity increased extracellular ADP level when ecto-F 1 -ATPase was activated by apoA-I. This increase in the bioavailability of extracellular ADP accordingly translated into an increase of HDL endocytosis on human hepatocytes. This study thus uncovered a new location and function of ANT for which activity at the cell surface of hepatocytes modulates the concentration of extracellular ADP and regulates HDL endocytosis. Copyright © 2017. Published by Elsevier B.V.

Intraindividual Variability in Test-Retest Air Displacement Plethysmography Measurements of Body Density for Men and Women.

PubMed

Gibson, Ann L; Roper, Jenevieve L; Mermier, Christine M

2016-10-01

Air displacement plethysmography (ADP) is a popular method for estimating body density (Db). Most ADP tests are performed once, with test-retest investigations scarce. Therefore, we investigated test-retest reliability of ADP. Active men (n = 25) and women (n = 25) volunteered and followed standard pretest guidelines. Participants wore dry, form-fitting swimwear and manufacturer-supplied swim caps. In a single session, two ADP trials with measured thoracic gas volume (TGV) were performed without repositioning participants. Separate 2 (sex) × 2 (ADP trial) repeated-measures ANOVAs were performed to investigate within-between comparisons of Db, TGV, body volume (Vb), and relative fatness (%BF). Paired t tests were used to investigate significant differences as appropriate. The Bland and Altman technique was used to depict individual intertrial variations. For all analyses, α =.05. A significant main effect for sex was found; men were lower in %BF and higher in all other variables compared with women. Individual variability was notable (ADP1-ADP2). The range of individual intertrial differences were larger for women than men, respectively, for Db (-0.0096-0.0045 g/cc; -0.0019-0.0054 g/cc), TGV (-0.623-1.325 L; -0.584-0.378 L), Vb (-0.249-2.10 L; -0.234-0.397 L), and %BF (-2.1-4.4%; -0.2-0.9%). When assessing body composition of women via ADP or using Db from ADP in a multicomponent model, at least two trials with measured TGV should be performed and the average of the values recorded and reported.

33 CFR 104.415 - Amendment and audit.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Amendment and audit. 104.415 Section 104.415 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MARITIME SECURITY MARITIME SECURITY: VESSELS Vessel Security Plan (VSP) § 104.415 Amendment and audit. (a) Amendments. (1) Amendments to a Vessel Security Plan...

Federal Plan for Cyber Security and Information Assurance Research and Development

DTIC Science & Technology

2006-04-01

Security Systems 103 varieties of the BB84 scheme have been developed, and other forms of quantum key distribution have been proposed. Rapid progress has led... key . Capability Gaps Existing quantum cryptographic protocols may also have weaknesses. Although BB84 is generally regarded as secure , researchers...complement agency-specific prioritization and R&D planning efforts in cyber security and information assurance. The Plan also describes the key Federal

ADP-ribosylation of proteins: Enzymology and biological significance

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

Althaus, F.R.; Richter, C.

1987-01-01

This book presents an overview of the molecular and biological consequences of the posttranslational modification of proteins with ADP-ribose monomers and polymers. Part one focuses on chromatin-associated poly ADP-ribosylation reactions which have evolved in higher eukaryotes as modulators of chromatin functions. The significance of poly ADP-ribosylation in DNA repair, carcinogenesis, and gene expression during terminal differentiation is discussed. Part two reviews mono ADP-ribosylation reactions which are catalyzed by prokaryotic and eukaryotic enzymes. Consideration is given to the action of bacterial toxins, such as cholera toxin, pertussis toxin, and diphtheria toxin. These toxins have emerged as tools for the molecular probingmore » of proteins involved in signal transduction and protein biosynthesis.« less

The Effect of Nucleotides and Inhibitors on Respiration in Isolated Wheat Mitochondria 1

PubMed Central

Pomeroy, M. Keith

1975-01-01

The effect of mono-, di-, and trinucleoside phosphates and respiratory inhibitors on respiration in winter wheat (Triticum aestivum L. cv. Rideau) mitochondria has been examined. When added during state 4 respiration, subsequent to addition of ADP, all of the dinucleotides stimulated oxidation and induced respiratory control with all substrates examined. Similar results were obtained with AMP, but other mononucleotides and all trinucleotides did not affect the rate of oxidation. Nucleoside diphosphates did not stimulate respiration when added prior to the addition of ADP, but subsequent addition of AMP, ADP, or ATP re-established coupled respiration in the presence of the dinucleotides. The duration of 2, 4-dinitrophenol stimulated respiration during oxidation of α-ketoglutarate was found to be dependent on the amount of AMP, ADP, or ATP added, either prior, or subsequent to, addition of the uncoupler. The addition of oligomycin during 2, 4-dinitrophenol stimulated respiration reestablished coupled respiration with low ADP/O ratios, when added after addition of ATP or conditions which allow formation of ATP from added ADP. The nucleoside diphosphates, other than ADP, did not stimulate oxidation of α-ketoglutarate in the presence of 2, 4-dinitrophenol until a small amount of adenine nucleotide was added to the system. The results suggest that dinucleotides other than ADP, are able to participate in the energy conversion processs of the mitochondria, probably via transphosphorylation reactions. Images PMID:16659027

Kinetics of nitrogenase of Klebsiella pneumoniae. Heterotropic interactions between magnesium-adenosine 5'-diphosphate and magnesium-adenosine 5'-triphosphate.

PubMed Central

Thorneley, R N; Cornish-Bowden, A

1977-01-01

The effects of MgADP and MgATP on the kinetics of a pre-steady-state electron-transfer reaction and on the steady-state kinetics of H2 evulution for nitrogenase proteins of K. pneumoniae were studied. MgADP was a competitive inhibitor of MgATP in the MgATP-induced electron transfer from the Fe-protein to the Mo-Fe-protein. A dissociation constant K'i = 20 micron was determined for MgADP. The release of MgADP or a coupled conformation change in the Fe-protein of K.pneumoniae occurred with a rate comparable with that of electron transfer, k approximately 2 X 10(2)S-1. Neither homotropic nor heterotropic interactions involving MgATP and MgADP were observed for this reaction. Steady-state kinetic data for H2 evolution exhibited heterotropic effects between MgADP and MgATP. The data have been fitted to symmetry and sequential-type models involving conformation changes in two identical subunits. The data suggest that the enzyme can bind up to molecules of either MgATP or MgADP, but is unable to bind both nucleotides simultaneously. The control of H2 evolution by the MgATP/MgADP ratio is not at the level of electron transfer between the Fe- and Mo-Fe-proteins. Images Fig. 2. PMID:336036

ARC-1993-AC93-0237-153

NASA Image and Video Library

1993-05-13

Pratt & Whitney Advanced Ducted Propulsor (ADP) Engine Test-590 in NASA Ames 40x80ft Subsonic Wind Tunnel. The Pratt & Whitney advanced ducted prop (ADP) demonstrator undergoing acoustic and fan performance testing. ADP technology could lead to decreased fuel consumption and noise.

Securing your financial future.

PubMed

Kachalia, Parag R

2009-04-01

Securing one's financial future requires dedication and planning. A clear plan must be implemented and continually re-examined to assure an individual remains on track to achieve this security. True success of the plan will be dependent upon taking the appropriate steps to protecting one's assets against unfortunate events along with building assets with a clear end goal in mind. This article will cover the fundamental steps an individual can take to secure their financial future.

75 FR 9622 - Southern Nuclear Operating Company, Inc.; Vogtle Electric Generating Plant, Units 1 and 2; Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-03

... requirements similar to those previously imposed by Commission orders issued after the terrorist attacks of... Security Plan, Training and Qualification Plan, Safeguards Contingency Plan, and Cyber Security Plan...

Protein Poly(ADP-ribosyl)ation Regulates Arabidopsis Immune Gene Expression and Defense Responses

PubMed Central

Feng, Baomin; Liu, Chenglong; de Oliveira, Marcos V. V.; Intorne, Aline C.; Li, Bo; Babilonia, Kevin; de Souza Filho, Gonçalo A.; Shan, Libo; He, Ping

2015-01-01

Perception of microbe-associated molecular patterns (MAMPs) elicits transcriptional reprogramming in hosts and activates defense to pathogen attacks. The molecular mechanisms underlying plant pattern-triggered immunity remain elusive. A genetic screen identified Arabidopsis poly(ADP-ribose) glycohydrolase 1 (atparg1) mutant with elevated immune gene expression upon multiple MAMP and pathogen treatments. Poly(ADP-ribose) glycohydrolase (PARG) is predicted to remove poly(ADP-ribose) polymers on acceptor proteins modified by poly(ADP-ribose) polymerases (PARPs) with three PARPs and two PARGs in Arabidopsis genome. AtPARP1 and AtPARP2 possess poly(ADP-ribose) polymerase activity, and the activity of AtPARP2 was enhanced by MAMP treatment. AtPARG1, but not AtPARG2, carries glycohydrolase activity in vivo and in vitro. Importantly, mutation (G450R) in atparg1 blocks its activity and the corresponding residue is highly conserved and essential for human HsPARG activity. Consistently, mutant atparp1atparp2 plants exhibited compromised immune gene activation and enhanced susceptibility to pathogen infections. Our study indicates that protein poly(ADP-ribosyl)ation plays critical roles in plant immune gene expression and defense to pathogen attacks. PMID:25569773

The nucleotide binding properties of human MSH2/MSH3 are lesion-dependent and distinct from those of human MSH2/MSH6

PubMed Central

Owen, Barbara A. L.; Lang, Walter; McMurray, Cynthia T.

2010-01-01

Summary Here, we report that MSH2/MSH3 maintains lesion specificity for small loops by a distinctly different mechanism than does MHSH2/MSH6 for single base mismatches. ADP and ATP have no preference for the subunits of hMSH2/MSH3. Upon lesion binding, however, hMSH2/MSH3 adopts a single “nucleotide signature” in which one ADP binds within the hMSH2 subunit and the hMSH3 subunit is empty. On the lesion, ADP-hMSH2/MSH3-empty binds and hydrolyzes ATP in the empty hMSH3 subunit, which reduces ADP affinity and increases ATP affinity for the hMSH2 subunit. ADP/ATP exchange converts (CA)4-loop-bound ADP-MSH2/MSH3-ATP into an ATP-hMSH2/MSH3-ADP intermediate in which ATP hydrolysis is inhibited in the hMSH2 subunit. We propose a model in which lesion binding converts hMSH2/MSH3 into a distinct nucleotide-bound form, and poises it to be a molecular sensor for lesion specificity. PMID:19377479

17 CFR 230.701 - Exemption for offers and sales of securities pursuant to certain compensatory benefit plans and...

Code of Federal Regulations, 2010 CFR

2010-04-01

... RULES AND REGULATIONS, SECURITIES ACT OF 1933 Regulation E-Exemption for Securities of Small Business... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Exemption for offers and sales of securities pursuant to certain compensatory benefit plans and contracts relating to compensation...

45 CFR 164.318 - Compliance dates for the initial implementation of the security standards.

Code of Federal Regulations, 2013 CFR

2013-10-01

... of Electronic Protected Health Information § 164.318 Compliance dates for the initial implementation of the security standards. (a) Health plan. (1) A health plan that is not a small health plan must... the security standards. 164.318 Section 164.318 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES...

45 CFR 164.318 - Compliance dates for the initial implementation of the security standards.

Code of Federal Regulations, 2012 CFR

2012-10-01

... of Electronic Protected Health Information § 164.318 Compliance dates for the initial implementation of the security standards. (a) Health plan. (1) A health plan that is not a small health plan must... the security standards. 164.318 Section 164.318 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES...

Information security management system planning for CBRN facilities

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

Lenaeu, Joseph D.; O'Neil, Lori Ross; Leitch, Rosalyn M.

The focus of this document is to provide guidance for the development of information security management system planning documents at chemical, biological, radiological, or nuclear (CBRN) facilities. It describes a risk-based approach for planning information security programs based on the sensitivity of the data developed, processed, communicated, and stored on facility information systems.

75 FR 51490 - Notice; Applications and Amendments to Facility Operating Licenses Involving Proposed No...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-20

...). The proposed amendment would approve the cyber security plan and implementation schedule, and revise... maintain in effect all provisions of the NRC-approved cyber security plan. Basis for proposed no... [facility operating license] to implement and maintain a Cyber Security Plan as part of Energy Northwest's...

75 FR 68831 - Notice; Applications and Amendments to Facility Operating Licenses Involving Proposed No...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-09

...-safeguards information (SUNSI). The amendments would approve the proposed Cyber Security Plan and... Commission-approved Cyber Security Plan as required by 10 CFR 73.54. Basis for proposed no significant... Facility Operating License (FOL) to implement and maintain a Cyber Security Plan as part of the facility's...

ARC-1901-AC93-0237-147

NASA Image and Video Library

1993-05-13

Pratt & Whitney Advanced Ducted Propulsor (ADP) Engine Test-590 in the NASA Ames 40x80ft Subsonic Wind Tunnel. The Pratt & Whitney Advanced Ducted Prop (ADP) demonstrator undergoing acoustic and fan performance testing. ADP technology could lead to decreased fuel consumption and noise.

Distribution of cytotoxic and DNA ADP-ribosylating activity in crude extracts from butterflies among the family Pieridae

PubMed Central

Matsumoto, Yasuko; Nakano, Tsuyoshi; Yamamoto, Masafumi; Matsushima-Hibiya, Yuko; Odagiri, Ken-Ichi; Yata, Osamu; Koyama, Kotaro; Sugimura, Takashi; Wakabayashi, Keiji

2008-01-01

Cabbage butterflies, Pieris rapae and Pieris brassicae, contain strong cytotoxic proteins, designated as pierisin-1 and -2, against cancer cell lines. These proteins exhibit DNA ADP-ribosylating activity. To determine the distribution of substances with cytotoxicity and DNA ADP-ribosylating activity among other species, crude extracts from 20 species of the family Pieridae were examined for cytotoxicity in HeLa cells and DNA ADP-ribosylating activity. Both activities were detected in extracts from 13 species: subtribes Pierina (Pieris rapae, Pieris canidia, Pieris napi, Pieris melete, Pieris brassicae, Pontia daplidice, and Talbotia naganum), Aporiina (Aporia gigantea, Aporia crataegi, Aporia hippia, and Delias pasithoe), and Appiadina (Appias nero and Appias paulina). All of these extracts contained substances recognized by anti-pierisin-1 antibodies, with a molecular mass of ≈100 kDa established earlier for pierisin-1. Moreover, sequences containing NAD-binding sites, conserved in ADP-ribosyltransferases, were amplified from genomic DNA from 13 species of butterflies with cytotoxicity and DNA ADP-ribosylating activity by PCR. Extracts from seven species, Appias lyncida, Leptosia nina, Anthocharis scolymus, Eurema hecabe, Catopsilia pomona, Catopsilia scylla, and Colias erate, showed neither cytotoxicity nor DNA ADP-ribosylating activity, and did not contain substances recognized by anti-pierisin-1 antibodies. Sequences containing NAD-binding sites were not amplified from genomic DNA from these seven species. Thus, pierisin-like proteins, showing cytotoxicity and DNA ADP-ribosylating activity, are suggested to be present in the extracts from butterflies not only among the subtribe Pierina, but also among the subtribes Aporiina and Appiadina. These findings offer insight to understanding the nature of DNA ADP-ribosylating activity in the butterfly. PMID:18256183

Analytical Design Package (ADP2): A computer aided engineering tool for aircraft transparency design

NASA Technical Reports Server (NTRS)

Wuerer, J. E.; Gran, M.; Held, T. W.

1994-01-01

The Analytical Design Package (ADP2) is being developed as a part of the Air Force Frameless Transparency Program (FTP). ADP2 is an integrated design tool consisting of existing analysis codes and Computer Aided Engineering (CAE) software. The objective of the ADP2 is to develop and confirm an integrated design methodology for frameless transparencies, related aircraft interfaces, and their corresponding tooling. The application of this methodology will generate high confidence for achieving a qualified part prior to mold fabrication. ADP2 is a customized integration of analysis codes, CAE software, and material databases. The primary CAE integration tool for the ADP2 is P3/PATRAN, a commercial-off-the-shelf (COTS) software tool. The open architecture of P3/PATRAN allows customized installations with different applications modules for specific site requirements. Integration of material databases allows the engineer to select a material, and those material properties are automatically called into the relevant analysis code. The ADP2 materials database will be composed of four independent schemas: CAE Design, Processing, Testing, and Logistics Support. The design of ADP2 places major emphasis on the seamless integration of CAE and analysis modules with a single intuitive graphical interface. This tool is being designed to serve and be used by an entire project team, i.e., analysts, designers, materials experts, and managers. The final version of the software will be delivered to the Air Force in Jan. 1994. The Analytical Design Package (ADP2) will then be ready for transfer to industry. The package will be capable of a wide range of design and manufacturing applications.

Comparison between the air displacement method and dual energy x-ray absorptiometry for estimation of body fat.

PubMed

Koda, M; Ando, F; Niino, N; Tsuzuku, S; Shimokata, H

2000-04-01

Air displacement plethysmography (ADP) is a method for the determining percent body fat (%BF) using the two-compartment model, in which the body is partitioned into body-fat mass and fat-free mass (FFM). Although this model assumes a constant density of FFM as 1.10 g/ml, its density may depend upon the bone mineral content (BMC) and total body water (TBW) which vary with age, gender, and race/ethnicity. This study compared %BF determined from ADP (ADP%BF) with %BF obtained by dual-energy x-ray absorptiometry (DXA%BF), and also investigated the effects of BMC, TBW, and other factors on its value. The subjects were 721 female and male Japanese aged 40 to 79 years. Body density was measured by ADP and %BF was calculated using Brozek et al's equation. BMC and body-fat volume were measured using DXA, and TBW was measured by multifrequency bioelectrical impedance. A series of anthropometric measurements was taken. Although ADP%BF was highly correlated with DXA%BF (female: r = 0.89, male: r = 0.90) (p < 0.001), ADP%BF differed significantly from DXA%BF (female: -1.30 +/- 0.14% (mean +/- s.e.m.), male: 1.22 +/- 0.13%) (p < 0.001). The difference in %BF (ADP%BF-DXA%BF) was negatively associated with BMC/FFM but not with TBW/FFM in both genders. The difference in %BF was also positively correlated with waist circumference. Considering previous studies, this result may be explained by the underestimation of DXA%BF, rather than by the overestimation of ADP%BF. In conclusion, ADP may be a useful method to measure %BF. However, BMC should be taken into consideration. Furthermore, DXA%BF may be underestimated in people with large waists.

Student experiences of the adolescent diversion project: a community-based exemplar in the pedagogy of service-learning.

PubMed

Davidson, William S; Jimenez, Tiffeny R; Onifade, Eyitayo; Hankins, Sean S

2010-12-01

Service-learning partnerships between universities and surrounding communities striving to create systems-level change must consider an emphasis in critical community service; a community centered paradigm where students are taught to work with communities to better understand contexts surrounding a social problem, as opposed to merely volunteering to provide a service to a community. The Adolescent Diversion Project (ADP), which has been operating for over 30 years, demonstrates critical community service through the type of relationship built between students and the local community. This article describes: a qualitative study with ADP students, the historical context of ADP, what and how students learned through their involvement in ADP, and reframes the work of this project as a form of service-learning pedagogy. Inductive content analysis was employed to identify underlying themes across participants related to their personal experiences of ADP and its impact in their lives. Findings were compared with service-learning outcomes and other quantitative studies conducted with past ADP cohorts from the literature. Consistent with past studies, ADP students become more negative toward social systems involved with their youth. This finding may explain an increase in feelings of political commitment following involvement in ADP. Consistent with service-learning outcomes, results demonstrate that ADP should be further documented as not only an effective community-based program but also as an exemplar in the pedagogy of service-learning. This study highlights why service-learning opportunities for students are not just one way to teach students, they are opportunities to bridge relationships within communities, bring life to theoretical concepts, and build the foundations necessary for educated citizens that will one day take lead roles in our society.

Nucleotide binding properties of bovine brain uncoating ATPase.

PubMed

Gao, B; Emoto, Y; Greene, L; Eisenberg, E

1993-04-25

Many functions of the 70-kDa heat-shock proteins (hsp70s) appear to be regulated by bound nucleotide. In this study we examined the nucleotide binding properties of purified bovine brain uncoating ATPase, one of the constitutively expressed members of the hsp70 family. We found that uncoating ATPase purified by ATP-agarose column chromatography retained one ADP molecule bound per enzyme molecule which could not be removed by extensive dialysis. Since this bound ADP exchanged rapidly with free ADP or ATP, the inability to remove the bound nucleotide was not due to slow dissociation but rather to strong binding of the nucleotide to the uncoating ATPase. In confirmation of this view, equilibrium dialysis experiments suggested that the dissociation constants for both ADP and ATP were less than 0.1 microM. Schmid et al. (Schmid, S. L., Braell, W. A., and Rothman, J. E. (1985) J. Biol. Chem 260, 10057-10062) suggested that the uncoating ATPase had two sites for bound nucleotide, one specific for ATP and one binding both ATP and ATP analogues but not ADP. In contrast, we found that enzyme with bound ADP did not bind further adenosine 5'-(beta,gamma-imino)triphosphate or dATP, nor did more than one ATP molecule bind per enzyme even in 200 microM free ATP. These results strongly suggest that the enzyme has only one binding site for nucleotide. During steady-state ATP hydrolysis, 85% of the bound nucleotide at this site was determined to be ATP and 15% ADP; this is consistent with the rate of ADP release determined in the exchange experiments noted above, where ADP release was found to be six times faster than the overall rate of ATP hydrolysis.

Environmental Assessment Addressing the Defense Language Institute English Language Center (DLIELC), and the Inter-American Air Forces Academy (IAAFA) Area Development Plan at Lackland Air Force Base, Texas

DTIC Science & Technology

2012-01-01

Heat island” refers to built up areas that have hotter surface and air temperatures than nearby rural areas. Heat island effect occurs when...Summary of Environmental Effects The public and regulatory agency scoping process focused the analysis on the following environmental resources... effects of implementing the DLIELC and IAAFA ADP are not significant, that preparation of an Environmental Impact Statement is unnecessary, and that a

The Naval Data Automation Command: A Case Study.

DTIC Science & Technology

1982-12-01

34commoa service" or as a "rescurce" to be mada available to users on a reimbur - sable basis and not n-c-ssarily owned and controlled by them. This was...cost reimbursable funding. "If feasible, i- is planned that users will budgmt and pay for NDP services and DPIs and DPPSOs of NAVDAC will be operated...chargeback system where the NARDAC is reimbursed for costs incurred). Services are provided in three general areas; ADP application system dev aonuent

General Plan Environmental Assessment for Joint Base Andrews-Naval Air Facility, Washington, Maryland

DTIC Science & Technology

2011-04-01

privatization of the water and natural gas systems and other utility systems , construction of the William B. Jones building, and the creation of...at the Upper Marlboro Branch Library of the Prince George’s County Memorial Library System at 14 730 Main St. Upper Marlboro, MD 20772 and on the...Wing 113 WG 113th Wing 316 WG 316th Wing 459 ARW 459th Air Refueling Wing AAM Annual Arithmetic Mean ACES Automated Civil Engineering System ADP

Strategic aspects of the purchasing process in the Finnish hearing instruments business.

PubMed

Petäjävaara, A

1995-01-01

Discusses the Finnish hearing instrument market which, in the past decade, has been characterized by both closed and shared markets. Indicates there has been some formal competition, but real price competition has not influenced the resharing of market shares. Finds that the current recession has forced hospitals to re-evaluate their purchasing criteria. Investigates the process with the help of industrial marketing theories to determine the strategic means which can be used to create competitive advantages. The new automatic data-processing (ADP)-based high technology in the hearing-instrument business provides opportunities for identifying these advantages. Surveys the abilities of hearing-centre personnel in university hospitals to take advantage of ADP-based tools. Shows that hearing-centre personnel have a low level of ADP knowledge and, thus, a great need for ADP training. Discusses the ADP-based strategy chosen to be AP Medical Hearing Ltd's main strategy and emphasizes the importance of ADP-based training in high technology.

Family-wide analysis of poly(ADP-ribose) polymerase activity

PubMed Central

Uchima, Lilen; Rood, Jenny; Zaja, Roko; Hay, Ronald T.; Ahel, Ivan; Chang, Paul

2014-01-01

The poly(ADP-ribose) polymerase (PARP) protein family generates ADP-ribose (ADPr) modifications onto target proteins using NAD+ as substrate. Based on the composition of three NAD+ coordinating amino acids, the H-Y-E motif, each PARP is predicted to generate either poly(ADP-ribose) (PAR) or mono(ADP-ribose) (MAR). However, the reaction product of each PARP has not been clearly defined, and is an important priority since PAR and MAR function via distinct mechanisms. Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. We identify automodification sites on seven PARPs, and demonstrate that MAR and PAR generating PARPs modify similar amino acids, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino acid targets. In addition, we identify cysteine as a novel amino acid target for ADP-ribosylation on PARPs. PMID:25043379

The Sound of Silence: RNAi in Poly (ADP-Ribose) Research

PubMed Central

Blenn, Christian; Wyrsch, Philippe; Althaus, Felix R.

2012-01-01

Poly(ADP-ribosyl)-ation is a nonprotein posttranslational modification of proteins and plays an integral part in cell physiology and pathology. The metabolism of poly(ADP-ribose) (PAR) is regulated by its synthesis by poly(ADP-ribose) polymerases (PARPs) and on the catabolic side by poly(ADP-ribose) glycohydrolase (PARG). PARPs convert NAD+ molecules into PAR chains that interact covalently or noncovalently with target proteins and thereby modify their structure and functions. PAR synthesis is activated when PARP1 and PARP2 bind to DNA breaks and these two enzymes account for almost all PAR formation after genotoxic stress. PARG cleaves PAR molecules into free PAR and finally ADP-ribose (ADPR) moieties, both acting as messengers in cellular stress signaling. In this review, we discuss the potential of RNAi to manipulate the levels of PARPs and PARG, and consequently those of PAR and ADPR, and compare the results with those obtained after genetic or chemical disruption. PMID:24705085

ADP Regulates SNF1, the Saccharomyces cerevisiae Homolog of AMP-Activated Protein Kinase

PubMed Central

Mayer, Faith V.; Heath, Richard; Underwood, Elizabeth; Sanders, Matthew J.; Carmena, David; McCartney, Rhonda R.; Leiper, Fiona C.; Xiao, Bing; Jing, Chun; Walker, Philip A.; Haire, Lesley F.; Ogrodowicz, Roksana; Martin, Stephen R.; Schmidt, Martin C.; Gamblin, Steven J.; Carling, David

2011-01-01

Summary The SNF1 protein kinase complex plays an essential role in regulating gene expression in response to the level of extracellular glucose in budding yeast. SNF1 shares structural and functional similarities with mammalian AMP-activated protein kinase. Both kinases are activated by phosphorylation on a threonine residue within the activation loop segment of the catalytic subunit. Here we show that ADP is the long-sought metabolite that activates SNF1 in response to glucose limitation by protecting the enzyme against dephosphorylation by Glc7, its physiologically relevant protein phosphatase. We also show that the regulatory subunit of SNF1 has two ADP binding sites. The tighter site binds AMP, ADP, and ATP competitively with NADH, whereas the weaker site does not bind NADH, but is responsible for mediating the protective effect of ADP on dephosphorylation. Mutagenesis experiments suggest that the general mechanism by which ADP protects against dephosphorylation is strongly conserved between SNF1 and AMPK. PMID:22019086

Two nucleotide binding sites modulate ( sup 3 H) glyburide binding to rat cortex membranes

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

Johnson, D.E.; Gopalakrishnan, M.; Triggle, D.J.

1991-03-11

The effects of nucleotides on the binding of the ATP-dependent K{sup +}-channel antagonist ({sup 3}H)glyburide (GLB) to rat cortex membranes were examined. Nucleotide triphosphates (NTPs) and nucleotide diphosphate (NDPs) inhibited the binding of GLB. This effect was dependent on the presence of dithiothreitol (DTT). Inhibition of binding by NTPs, with the exception of ATP{gamma}S, was dependent on the presence of Mg{sup 2+}. GLB binding showed a biphasic response to ADP: up to 3 mM, ADP inhibited binding, and above this concentration GLB binding increased rapidly, and was restored to normal levels by 10 mM ADP. In the presence of Mg{supmore » 2+}, ADP did not stimulate binding. Saturation analysis in the presence of Mg{sup 2+} and increasing concentrations of ADP showed that ADP results primarily in a change of the B{sub max} for GLB binding. The differential effects of NTPS and NDPs indicate that two nucleotide binding sites regulate GLB binding.« less

FY 2016 - Stockpile Stewardship and Management Plan

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

None

2015-03-01

This Department of Energy’s (DOE) National Nuclear Security Administration (NNSA) Fiscal Year Stockpile Stewardship and Management Plan (SSMP) is a key planning document for the nuclear security enterprise.

78 FR 10211 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Securities...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-13

... for OMB Review; Comment Request; Securities Lending by Employee Benefit Plans ACTION: Notice. SUMMARY...) sponsored information collection request (ICR) titled, ``Securities Lending by Employee Benefit Plans,'' [email protected] . Authority: 44 U.S.C. 3507(a)(1)(D). SUPPLEMENTARY INFORMATION: The Securities Lending by...

Pleiotropic regulatory genes bldA, adpA and absB are implicated in production of phosphoglycolipid antibiotic moenomycin.

PubMed

Makitrynskyy, Roman; Ostash, Bohdan; Tsypik, Olga; Rebets, Yuriy; Doud, Emma; Meredith, Timothy; Luzhetskyy, Andriy; Bechthold, Andreas; Walker, Suzanne; Fedorenko, Victor

2013-10-23

Unlike the majority of actinomycete secondary metabolic pathways, the biosynthesis of peptidoglycan glycosyltransferase inhibitor moenomycin in Streptomyces ghanaensis does not involve any cluster-situated regulators (CSRs). This raises questions about the regulatory signals that initiate and sustain moenomycin production. We now show that three pleiotropic regulatory genes for Streptomyces morphogenesis and antibiotic production-bldA, adpA and absB-exert multi-layered control over moenomycin biosynthesis in native and heterologous producers. The bldA gene for tRNA(Leu)UAA is required for the translation of rare UUA codons within two key moenomycin biosynthetic genes (moe), moeO5 and moeE5. It also indirectly influences moenomycin production by controlling the translation of the UUA-containing adpA and, probably, other as-yet-unknown repressor gene(s). AdpA binds key moe promoters and activates them. Furthermore, AdpA interacts with the bldA promoter, thus impacting translation of bldA-dependent mRNAs-that of adpA and several moe genes. Both adpA expression and moenomycin production are increased in an absB-deficient background, most probably because AbsB normally limits adpA mRNA abundance through ribonucleolytic cleavage. Our work highlights an underappreciated strategy for secondary metabolism regulation, in which the interaction between structural genes and pleiotropic regulators is not mediated by CSRs. This strategy might be relevant for a growing number of CSR-free gene clusters unearthed during actinomycete genome mining.

Quantification of diphtheria toxin mediated ADP-ribosylation in a solid-phase assay.

PubMed

Bachran, Christopher; Sutherland, Mark; Bachran, Diana; Fuchs, Hendrik

2007-09-01

Because of reduced vaccination programs, the number of diphtheria infections has increased in the last decade. Diphtheria toxin (DT) is expressed by Corynebacterium diphtheriae and is responsible for the lethality of diphtheria. DT inhibits cellular protein synthesis by ADP-ribosylation of the eukaryotic elongation factor 2 (eEF2). No in vitro system for the quantification of DT enzymatic activity exists. We developed a solid-phase assay for the specific detection of ADP-ribosylation by DT. Solid phase-bound his-tag eEF2 is ADP-ribosylated by toxins using biotinylated NAD(+) as substrate, and the transferred biotinylated ADP-ribose is detected by streptavidin-peroxidase. DT enzymatic activity correlated with absorbance. We measured the amount of ADP-ribosylated eEF2 after precipitation with streptavidin-Sepharose. Quantification was done after Western blotting and detection with anti-his-tag antibody using an LAS-1000 System. The assay detected enzymatically active DT at 30 ng/L, equivalent to 5 mU/L ADP-ribosylating activity. Pseudomonas exotoxin A (PE) activity was also detected at 100 ng/L. We verified the assay with chimeric toxins composed of the catalytic domain of DT or PE and a tumor-specific ligand. These chimeric toxins revealed increased signals at 1000 ng/L. Heat-inactivated DT and cholera toxin that ADP-ribosylates G-proteins did not show any signal increase. The assay may be the basis for the development of a routine diagnostic assay for the detection of DT activity and highly specific inhibitors of DT.

Nicotinamide megadosing increases hepatic poly(ADP-ribose) levels in choline-deficient rats.

PubMed

ApSimon, M M; Rawling, J M; Kirkland, J B

1995-07-01

Previous work in our laboratory has shown that dietary megadoses of nicotinamide, used in the prevention of diabetes, cause increases in hepatic poly(ADP-ribose). Poly(ADP-ribose) is synthesized from NAD+ by a nuclear enzyme, poly(ADP-ribose)polymerase, which is activated by DNA strand breaks. The nicotinamide-induced increase in poly(ADP-ribose) could result from an increase in substrate, NAD+, or the induction of strand breaks in DNA. Strand breaks may result from the depletion of single carbon groups, through the excretion of methylated derivatives of nicotinamide. To differentiate between these mechanisms, a 3 x 3 factorial experiment was conducted in which rats were fed diets containing various supplements of choline bitartrate (0, 2, 20 g/kg diet) and nicotinamide (0, 1, 2 g/kg diet). At the conclusion of treatments, blood NAD+ and liver lipid, NAD+ and poly(ADP-ribose) levels were determined. Choline deficiency caused the characteristic accumulation of fat in the liver at all levels of nicotinamide. In choline deficient rats, nicotinamide supplements further increased liver lipid concentration. Blood and liver NAD+ concentrations were increased by nicotinamide supplementation, irrespective of choline status. In contrast, liver poly(ADP-ribose) levels were increased by nicotinamide supplementation only in choline deficient rats. These results show that nicotinamide-induced increases in poly(ADP-ribose) levels appear to be dependent on decreased methyl donor status and suggest that adequate choline status is important for preventing some deleterious effects of nicotinamide treatment.

A terrorism response plan for hospital security and safety officers.

PubMed

White, Donald E

2002-01-01

Security and Safety managers in today's healthcare facilities need to factor terrorism response into their emergency management plans, separate from the customary disaster plans and the comparatively recent security plans. Terrorism incidents will likely be security occurrences that use a weapon of mass destruction to magnify the incidents into disasters. Facility Y2K Plans can provide an excellent framework for the detailed contingency planning needed for terrorism response by healthcare facilities. Tabbed binder notebooks, with bulleted procedures and contact points for each functional section, can provide security and safety officers with at-a-glance instructions for quick 24/7 implementation. Each functional section should focus upon what activities or severity levels trigger activation of the backup processes. Network with your countywide, regional, and/or state organizations to learn what your peers are doing. Comprehensively inventory your state, local, and commercial resources so that you have alternate providers readily available 24/7 to assist your facility upon disasters.

45 CFR 95.621 - ADP reviews.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false ADP reviews. 95.621 Section 95.621 Public Welfare....621 ADP reviews. The Department will conduct periodic onsite surveys and reviews of State and local... the Department and State or local agencies prior to conducting such surveys or reviews, which may...

Very-Near-Field Plume Model of a Hall Thruster

DTIC Science & Technology

2003-07-20

UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP014988 TITLE: Very-Near-Field Plume Model of a Hall Thruster DISTRIBUTION...numbers comprise the compilation report: ADP014936 thru ADP015049 UNCLASSIFIED am 46 Very-Near-Field Plume Model of a Hall Thruster F. Taccogna’, S. LongoŖ

The effects of vincristine on platelet aggregation studied by a filter loop technique in the rat.

PubMed Central

Bee, D.; Leach, E.; Martin, J. F.; Suggett, A. J.

1980-01-01

1 A method for measuring aggregation of platelets of adenosine diphosphate (ADP) is described using a filter inserted into the flowing aortic blood in the rat. 2 Repeated infusions of ADP resulted in a fall in the calculated aggregation index without significant changes in the platelet count. 3 Vincristine (0.05 mg/kg) intravenously caused significant inhibition of ADP-induced platelet aggregation. 4 Infusion of ADP caused some peripheral vasodilatation though it is unlikely that this contributed to the effects seen to any great extent. PMID:7437636

An Analysis of the General Services Administration Board of Contract Appeals Bid Protest Decisions and the Effect on Automated Data Processing Equipment/Federal Information Processing Resources Procurements

DTIC Science & Technology

1991-12-01

associated with ADP/FIP protests. Navy and Marine Corps contracting agencies w\\ere contacted to determine their current experience in ADP/’FIP contracting...an emphasis on the GSBCA. A protestor has many options in vhich to "avenge" their wrong. A Contracting Officer can therefore expect a variety of...subject to their exclusive procurement authority. The term ADPE and ADP/FIP will be used somewhat loosely. In most cases, the acronyms include

Follow-On Technology Requirement Study for Advanced Subsonic Transport

NASA Technical Reports Server (NTRS)

Wendus, Bruce E.; Stark, Donald F.; Holler, Richard P.; Funkhouser, Merle E.

2003-01-01

A study was conducted to define and assess the critical or enabling technologies required for a year 2005 entry into service (EIS) engine for subsonic commercial aircraft, with NASA Advanced Subsonic Transport goals used as benchmarks. The year 2005 EIS advanced technology engine is an Advanced Ducted Propulsor (ADP) engine. Performance analysis showed that the ADP design offered many advantages compared to a baseline turbofan engine. An airplane/ engine simulation study using a long range quad aircraft quantified the effects of the ADP engine on the economics of typical airline operation. Results of the economic analysis show the ADP propulsion system provides a 6% reduction in direct operating cost plus interest, with half the reduction resulting from reduced fuel consumption. Critical and enabling technologies for the year 2005 EIS ADP were identified and prioritized.

Monitoring of the ADP/ATP Ratio by Induced Circularly Polarised Europium Luminescence.

PubMed

Shuvaev, Sergey; Fox, Mark A; Parker, David

2018-06-18

A series of three europium complexes bearing picolyl amine moieties was found to possess differing binding affinities towards Zn 2+ and three nucleotides: AMP, ADP, and ATP. A large increase in the total emission intensity was observed upon binding Zn 2+ , followed by signal amplification upon the addition of nucleotides. The resulting adducts possessed strong induced circularly polarised emission, with ADP and ATP signals of opposite sign. Model DFT geometries of the adducts suggest the Δ diastereoisomer is preferred for ATP and the Λ isomer for ADP/AMP. This change in sign allows the ADP/ATP (or AMP/ATP) ratio to be assessed by monitoring changes in the emission dissymmetry factor, g em . © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases.

PubMed

Hassa, Paul O; Hottiger, Michael O

2008-01-01

Poly-ADP-ribose metabolism plays a mayor role in a wide range of biological processes, such as maintenance of genomic stability, transcriptional regulation, energy metabolism and cell death. Poly-ADP-ribose polymerases (PARPs) are an ancient family of enzymes, as evidenced by the poly-ADP-ribosylating activities reported in dinoflagellates and archaebacteria and by the identification of Parp-like genes in eubacterial and archaeabacterial genomes. Six genes encoding "bona fide" PARP enzymes have been identified in mammalians: PARP1, PARP2, PARP3, PARP4/vPARP, PARP5/Tankyrases-1 and PARP6/Tankyrases-2. The best studied of these enzymes PARP1 plays a primary role in the process of poly-ADP-ribosylation. PARP1-mediated poly-ADP-ribosylation has been implicated in the pathogenesis of cancer, inflammatory and neurodegenerative disorders. This review will summarize the novel findings and concepts for PARP enzymes and their poly-ADP-ribosylation activity in the regulation of physiological and pathophysiological processes. A special focus is placed on the proposed molecular mechanisms involved in these processes, such as signaling, regulation of telomere dynamics, remodeling of chromatin structure and transcriptional regulation. A potential functional cross talk between PARP family members and other NAD+-consuming enzymes is discussed.

The nucleotide binding dynamics of human MSH2-MSH3 are lesion dependent.

PubMed

Owen, Barbara A L; H Lang, Walter; McMurray, Cynthia T

2009-05-01

Here we report that the human DNA mismatch complex MSH2-MSH3 recognizes small loops by a mechanism different from that of MSH2-MSH6 for single-base mismatches. The subunits MSH2 and MSH3 can bind either ADP or ATP with similar affinities. Upon binding to a DNA loop, however, MSH2-MSH3 adopts a single 'nucleotide signature', in which the MSH2 subunit is occupied by an ADP molecule and the MSH3 subunit is empty. Subsequent ATP binding and hydrolysis in the MSH3 subunit promote ADP-ATP exchange in the MSH2 subunit to yield a hydrolysis-independent ATP-MSH2-MSH3-ADP intermediate. Human MSH2-MSH3 and yeast Msh2-Msh6 both undergo ADP-ATP exchange in the Msh2 subunit but, apparently, have opposite requirements for ATP hydrolysis: ADP release from DNA-bound Msh2-Msh6 requires ATP stabilization in the Msh6 subunit, whereas ADP release from DNA-bound MSH2-MSH3 requires ATP hydrolysis in the MSH3 subunit. We propose a model in which lesion binding converts MSH2-MSH3 into a distinct nucleotide-bound form that is poised to be a molecular sensor for lesion specificity.

Nucleoside pyrophosphatase activity associated with pig kidney alkaline phosphatase

PubMed Central

Wass, Milica; Butterworth, P. J.

1971-01-01

1. A study was made of the hydrolysis, at pH9.0, of ATP and ADP catalysed by pig kidney alkaline phosphatase. Both of these nucleoside pyrophosphates are substrates for the enzyme; Km values are 4×10−5m for ATP and 6.3×10−5m for ADP. Vmax. for ADP is approximately double that of ATP. 2. Above 0.1mm approximately, both ATP and ADP are inhibitory, but the inhibition is reversible by the addition of Mg2+ ions to form MgATP2− or MgADP− complexes. The complexes, besides being non-inhibitory, are also substrates for the enzyme with Km values identical with those of the respective free nucleotides. 3. Mg2+ ions are inhibitory when present in excess of ATP or ADP. The degree of inhibition is greater with ATP as substrate, but with both ATP and ADP a mixed competitive–non-competitive type of inhibition is observed. 4. It is suggested that under normal conditions the enzyme is inhibited by cellular concentrations of ATP plus ADP but that an increase in the concentration of Mg2+ ions stimulates activity by relieving nucleoside pyrophosphate inhibition. The properties may be of importance in the regulation of the transport of bivalent cations. PMID:4331861

Port Security: A National Planning Guide

DOT National Transportation Integrated Search

1997-01-01

Port Security: A National Planning Guide has been produced for the purpose of conveying the United States Department of Transportations policy perspective on port security to the maritime community. This guide provides an overview of the essential as...

47 CFR 87.395 - Plan for the Security Control of Air Traffic and Air Navigation Aids (Short Title: SCATANA).

Code of Federal Regulations, 2012 CFR

2012-10-01

... and Air Navigation Aids (Short Title: SCATANA). 87.395 Section 87.395 Telecommunication FEDERAL... Communications § 87.395 Plan for the Security Control of Air Traffic and Air Navigation Aids (Short Title: SCATANA). (a) The Plan for the Security Control of Air Traffic and Air Navigation Aids (SCATANA) is...

47 CFR 87.395 - Plan for the Security Control of Air Traffic and Air Navigation Aids (Short Title: SCATANA).

Code of Federal Regulations, 2014 CFR

2014-10-01

... and Air Navigation Aids (Short Title: SCATANA). 87.395 Section 87.395 Telecommunication FEDERAL... Communications § 87.395 Plan for the Security Control of Air Traffic and Air Navigation Aids (Short Title: SCATANA). (a) The Plan for the Security Control of Air Traffic and Air Navigation Aids (SCATANA) is...

47 CFR 87.395 - Plan for the Security Control of Air Traffic and Air Navigation Aids (Short Title: SCATANA).

Code of Federal Regulations, 2013 CFR

2013-10-01

... and Air Navigation Aids (Short Title: SCATANA). 87.395 Section 87.395 Telecommunication FEDERAL... Communications § 87.395 Plan for the Security Control of Air Traffic and Air Navigation Aids (Short Title: SCATANA). (a) The Plan for the Security Control of Air Traffic and Air Navigation Aids (SCATANA) is...

47 CFR 87.395 - Plan for the Security Control of Air Traffic and Air Navigation Aids (Short Title: SCATANA).

Code of Federal Regulations, 2011 CFR

2011-10-01

... and Air Navigation Aids (Short Title: SCATANA). 87.395 Section 87.395 Telecommunication FEDERAL... Communications § 87.395 Plan for the Security Control of Air Traffic and Air Navigation Aids (Short Title: SCATANA). (a) The Plan for the Security Control of Air Traffic and Air Navigation Aids (SCATANA) is...

47 CFR 87.395 - Plan for the Security Control of Air Traffic and Air Navigation Aids (Short Title: SCATANA).

Code of Federal Regulations, 2010 CFR

2010-10-01

... and Air Navigation Aids (Short Title: SCATANA). 87.395 Section 87.395 Telecommunication FEDERAL... Communications § 87.395 Plan for the Security Control of Air Traffic and Air Navigation Aids (Short Title: SCATANA). (a) The Plan for the Security Control of Air Traffic and Air Navigation Aids (SCATANA) is...

12 CFR 218.776 - Exemption from the definition of “broker” for banks effecting certain excepted or exempted...

Code of Federal Regulations, 2010 CFR

2010-01-01

... certain excepted or exempted transactions in a company's securities for its employee benefit plans. (a) A... an employee benefit plan account; (3) Any such security is obtained directly from: (i) The company; or (ii) An employee benefit plan of the company; and (4) Any such security is transferred only to: (i...

Comparison of air displacement plethysmography to hydrostatic weighing for estimating total body density in children.

PubMed

Claros, Geo; Hull, Holly R; Fields, David A

2005-09-09

The purpose of this study was to examine the accuracy of total body density and percent body fat (% fat) using air displacement plethysmography (ADP) and hydrostatic weighing (HW) in children. Sixty-six male and female subjects (40 males: 12.4 +/- 1.3 yrs, 47.4 +/- 14.8 kg, 155.4 +/- 11.9 cm, 19.3 +/- 4.1 kg/m2; 26 females: 12.0 +/- 1.9 yrs, 41.4 +/- 7.7 kg, 152.1 +/- 8.9 cm, 17.7 +/- 1.7 kg/m2) were tested using ADP and HW with ADP always preceding HW. Accuracy, precision, and bias were examined in ADP with HW serving as the criterion method. Lohman's equations that are child specific for age and gender were used to convert body density to % fat. Regression analysis determined the accuracy of ADP and potential bias between ADP and HW using Bland-Altman analysis. For the entire group (Y = 0.835x + 0.171, R2 = 0.84, SEE = 0.007 g/cm3) and for the males (Y = 0.837x + 0.174, R2 = 0.90, SEE = 0.006 g/cm3) the regression between total body density by HW and by ADP significantly deviated from the line of identity. However in females, the regression between total body density by HW and ADP did not significantly deviate from the line of identity (Y = 0.750x + 0.258, R2 = 0.55, SEE = 0.008 g/cm3). The regression between % fat by HW and ADP for the group (Y = 0.84x + 3.81, R2 = 0.83, SEE = 3.35 % fat) and for the males (Y = 0.84x + 3.25, R2 = 0.90, SEE = 3.00 % fat) significantly deviated from the line of identity. However, in females the regression between % fat by HW and ADP did not significantly deviate from the line of identity (Y = 0.81x + 5.17, R2 = 0.56, SEE = 3.80 % fat). Bland-Altman analysis revealed no bias between HW total body density and ADP total body density for the entire group (R = 0.-22; P = 0.08) or for females (R = 0.02; P = 0.92), however bias existed in males (R = -0.37; P < or = 0.05). Bland-Altman analysis revealed no bias between HW and ADP % fat for the entire group (R = 0.21; P = 0.10) or in females (R = 0.10; P = 0.57), however bias was indicated for males by a significant correlation (R = 0.36; P < or = 0.05), with ADP underestimating % fat at lower fat values and overestimating at the higher % fat values. A significant difference in total body density and % fat was observed between ADP and HW in children 10-15 years old with a potential gender difference being detected. Upon further investigation it was revealed that the study was inadequately powered, thus we recommend that larger studies that are appropriately powered be conducted to better understand this potential gender difference.

Comparison of air displacement plethysmography to hydrostatic weighing for estimating total body density in children

PubMed Central

Claros, Geo; Hull, Holly R; Fields, David A

2005-01-01

Background The purpose of this study was to examine the accuracy of total body density and percent body fat (% fat) using air displacement plethysmography (ADP) and hydrostatic weighing (HW) in children. Methods Sixty-six male and female subjects (40 males: 12.4 ± 1.3 yrs, 47.4 ± 14.8 kg, 155.4 ± 11.9 cm, 19.3 ± 4.1 kg/m2; 26 females: 12.0 ± 1.9 yrs, 41.4 ± 7.7 kg, 152.1 ± 8.9 cm, 17.7 ± 1.7 kg/m2) were tested using ADP and HW with ADP always preceding HW. Accuracy, precision, and bias were examined in ADP with HW serving as the criterion method. Lohman's equations that are child specific for age and gender were used to convert body density to % fat. Regression analysis determined the accuracy of ADP and potential bias between ADP and HW using Bland-Altman analysis. Results For the entire group (Y = 0.835x + 0.171, R2 = 0.84, SEE = 0.007 g/cm3) and for the males (Y = 0.837x + 0.174, R2 = 0.90, SEE = 0.006 g/cm3) the regression between total body density by HW and by ADP significantly deviated from the line of identity. However in females, the regression between total body density by HW and ADP did not significantly deviate from the line of identity (Y = 0.750x + 0.258, R2 = 0.55, SEE = 0.008 g/cm3). The regression between % fat by HW and ADP for the group (Y = 0.84x + 3.81, R2 = 0.83, SEE = 3.35 % fat) and for the males (Y = 0.84x + 3.25, R2 = 0.90, SEE = 3.00 % fat) significantly deviated from the line of identity. However, in females the regression between % fat by HW and ADP did not significantly deviate from the line of identity (Y = 0.81x + 5.17, R2 = 0.56, SEE = 3.80 % fat). Bland-Altman analysis revealed no bias between HW total body density and ADP total body density for the entire group (R = 0.-22; P = 0.08) or for females (R = 0.02; P = 0.92), however bias existed in males (R = -0.37; P ≤ 0.05). Bland-Altman analysis revealed no bias between HW and ADP % fat for the entire group (R = 0.21; P = 0.10) or in females (R = 0.10; P = 0.57), however bias was indicated for males by a significant correlation (R = 0.36; P ≤ 0.05), with ADP underestimating % fat at lower fat values and overestimating at the higher % fat values. Conclusion A significant difference in total body density and % fat was observed between ADP and HW in children 10–15 years old with a potential gender difference being detected. Upon further investigation it was revealed that the study was inadequately powered, thus we recommend that larger studies that are appropriately powered be conducted to better understand this potential gender difference. PMID:16153297

Synergistic role of ADP and Ca2+ in diastolic myocardial stiffness

PubMed Central

Sequeira, Vasco; Najafi, Aref; McConnell, Mark; Fowler, Ewan D; Bollen, Ilse A E; Wüst, Rob C I; dos Remedios, Cris; Helmes, Michiel; White, Ed; Stienen, Ger J M; Tardiff, Jil; Kuster, Diederik W D; van der Velden, Jolanda

2015-01-01

Abstract Heart failure (HF) with diastolic dysfunction has been attributed to increased myocardial stiffness that limits proper filling of the ventricle. Altered cross-bridge interaction may significantly contribute to high diastolic stiffness, but this has not been shown thus far. Cross-bridge interactions are dependent on cytosolic [Ca2+] and the regeneration of ATP from ADP. Depletion of myocardial energy reserve is a hallmark of HF leading to ADP accumulation and disturbed Ca2+ handling. Here, we investigated if ADP elevation in concert with increased diastolic [Ca2+] promotes diastolic cross-bridge formation and force generation and thereby increases diastolic stiffness. ADP dose-dependently increased force production in the absence of Ca2+ in membrane-permeabilized cardiomyocytes from human hearts. Moreover, physiological levels of ADP increased actomyosin force generation in the presence of Ca2+ both in human and rat membrane-permeabilized cardiomyocytes. Diastolic stress measured at physiological lattice spacing and 37°C in the presence of pathological levels of ADP and diastolic [Ca2+] revealed a 76 ± 1% contribution of cross-bridge interaction to total diastolic stress in rat membrane-permeabilized cardiomyocytes. Inhibition of creatine kinase (CK), which increases cytosolic ADP, in enzyme-isolated intact rat cardiomyocytes impaired diastolic re-lengthening associated with diastolic Ca2+ overload. In isolated Langendorff-perfused rat hearts, CK inhibition increased ventricular stiffness only in the presence of diastolic [Ca2+]. We propose that elevations of intracellular ADP in specific types of cardiac disease, including those where myocardial energy reserve is limited, contribute to diastolic dysfunction by recruiting cross-bridges, even at low Ca2+, and thereby increase myocardial stiffness. Key points Diastolic dysfunction in heart failure patients is evident from stiffening of the passive properties of the ventricular wall. Increased actomyosin interactions may significantly limit diastolic capacity, however, direct evidence is absent. From experiments at the cellular and whole organ level, in humans and rats, we show that actomyosin-related force development contributes significantly to high diastolic stiffness in environments where high ADP and increased diastolic [Ca2+] are present, such as the failing myocardium. Our basal study provides a mechanical mechanism which may partly underlie diastolic dysfunction. PMID:26096258

Structural basis for lack of ADP-ribosyltransferase activity in poly(ADP-ribose) polymerase-13/zinc finger antiviral protein.

PubMed

Karlberg, Tobias; Klepsch, Mirjam; Thorsell, Ann-Gerd; Andersson, C David; Linusson, Anna; Schüler, Herwig

2015-03-20

The mammalian poly(ADP-ribose) polymerase (PARP) family includes ADP-ribosyltransferases with diphtheria toxin homology (ARTD). Most members have mono-ADP-ribosyltransferase activity. PARP13/ARTD13, also called zinc finger antiviral protein, has roles in viral immunity and microRNA-mediated stress responses. PARP13 features a divergent PARP homology domain missing a PARP consensus sequence motif; the domain has enigmatic functions and apparently lacks catalytic activity. We used x-ray crystallography, molecular dynamics simulations, and biochemical analyses to investigate the structural requirements for ADP-ribosyltransferase activity in human PARP13 and two of its functional partners in stress granules: PARP12/ARTD12, and PARP15/BAL3/ARTD7. The crystal structure of the PARP homology domain of PARP13 shows obstruction of the canonical active site, precluding NAD(+) binding. Molecular dynamics simulations indicate that this closed cleft conformation is maintained in solution. Introducing consensus side chains in PARP13 did not result in 3-aminobenzamide binding, but in further closure of the site. Three-dimensional alignment of the PARP homology domains of PARP13, PARP12, and PARP15 illustrates placement of PARP13 residues that deviate from the PARP family consensus. Introducing either one of two of these side chains into the corresponding positions in PARP15 abolished PARP15 ADP-ribosyltransferase activity. Taken together, our results show that PARP13 lacks the structural requirements for ADP-ribosyltransferase activity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Comprehensive Fault Tolerance and Science-Optimal Attitude Planning for Spacecraft Applications

NASA Astrophysics Data System (ADS)

Nasir, Ali

Spacecraft operate in a harsh environment, are costly to launch, and experience unavoidable communication delay and bandwidth constraints. These factors motivate the need for effective onboard mission and fault management. This dissertation presents an integrated framework to optimize science goal achievement while identifying and managing encountered faults. Goal-related tasks are defined by pointing the spacecraft instrumentation toward distant targets of scientific interest. The relative value of science data collection is traded with risk of failures to determine an optimal policy for mission execution. Our major innovation in fault detection and reconfiguration is to incorporate fault information obtained from two types of spacecraft models: one based on the dynamics of the spacecraft and the second based on the internal composition of the spacecraft. For fault reconfiguration, we consider possible changes in both dynamics-based control law configuration and the composition-based switching configuration. We formulate our problem as a stochastic sequential decision problem or Markov Decision Process (MDP). To avoid the computational complexity involved in a fully-integrated MDP, we decompose our problem into multiple MDPs. These MDPs include planning MDPs for different fault scenarios, a fault detection MDP based on a logic-based model of spacecraft component and system functionality, an MDP for resolving conflicts between fault information from the logic-based model and the dynamics-based spacecraft models" and the reconfiguration MDP that generates a policy optimized over the relative importance of the mission objectives versus spacecraft safety. Approximate Dynamic Programming (ADP) methods for the decomposition of the planning and fault detection MDPs are applied. To show the performance of the MDP-based frameworks and ADP methods, a suite of spacecraft attitude planning case studies are described. These case studies are used to analyze the content and behavior of computed policies in response to the changes in design parameters. A primary case study is built from the Far Ultraviolet Spectroscopic Explorer (FUSE) mission for which component models and their probabilities of failure are based on realistic mission data. A comparison of our approach with an alternative framework for spacecraft task planning and fault management is presented in the context of the FUSE mission.

Management of a stage-structured insect pest: an application of approximate optimization.

PubMed

Hackett, Sean C; Bonsall, Michael B

2018-06-01

Ecological decision problems frequently require the optimization of a sequence of actions over time where actions may have both immediate and downstream effects. Dynamic programming can solve such problems only if the dimensionality is sufficiently low. Approximate dynamic programming (ADP) provides a suite of methods applicable to problems of arbitrary complexity at the expense of guaranteed optimality. The most easily generalized method is the look-ahead policy: a brute-force algorithm that identifies reasonable actions by constructing and solving a series of temporally truncated approximations of the full problem over a defined planning horizon. We develop and apply this approach to a pest management problem inspired by the Mediterranean fruit fly, Ceratitis capitata. The model aims to minimize the cumulative costs of management actions and medfly-induced losses over a single 16-week season. The medfly population is stage-structured and grows continuously while management decisions are made at discrete, weekly intervals. For each week, the model chooses between inaction, insecticide application, or one of six sterile insect release ratios. Look-ahead policy performance is evaluated over a range of planning horizons, two levels of crop susceptibility to medfly and three levels of pesticide persistence. In all cases, the actions proposed by the look-ahead policy are contrasted to those of a myopic policy that minimizes costs over only the current week. We find that look-ahead policies always out-performed a myopic policy and decision quality is sensitive to the temporal distribution of costs relative to the planning horizon: it is beneficial to extend the planning horizon when it excludes pertinent costs. However, longer planning horizons may reduce decision quality when major costs are resolved imminently. ADP methods such as the look-ahead-policy-based approach developed here render questions intractable to dynamic programming amenable to inference but should be applied carefully as their flexibility comes at the expense of guaranteed optimality. However, given the complexity of many ecological management problems, the capacity to propose a strategy that is "good enough" using a more representative problem formulation may be preferable to an optimal strategy derived from a simplified model. © 2018 by the Ecological Society of America.

Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP, ADP, and Mg2+.

PubMed

Michailova, Anushka; Saucerman, Jeffrey; Belik, Mary Ellen; McCulloch, Andrew D

2005-03-01

Changes in cytosolic free Mg(2+) and adenosine nucleotide phosphates affect cardiac excitability and contractility. To investigate how modulation by Mg(2+), ATP, and ADP of K(ATP) and L-type Ca(2+) channels influences excitation-contraction coupling, we incorporated equations for intracellular ATP and MgADP regulation of the K(ATP) current and MgATP regulation of the L-type Ca(2+) current in an ionic-metabolic model of the canine ventricular myocyte. The new model: 1), quantitatively reproduces a dose-response relationship for the effects of changes in ATP on K(ATP) current, 2), simulates effects of ADP in modulating ATP sensitivity of K(ATP) channel, 3), predicts activation of Ca(2+) current during rapid increase in MgATP, and 4), demonstrates that decreased ATP/ADP ratio with normal total Mg(2+) or increased free Mg(2+) with normal ATP and ADP activate K(ATP) current, shorten action potential, and alter ionic currents and intracellular Ca(2+) signals. The model predictions are in agreement with experimental data measured under normal and a variety of pathological conditions.

Loss of the Mono-ADP-ribosyltransferase, Tiparp, Increases Sensitivity to Dioxin-induced Steatohepatitis and Lethality*

PubMed Central

Ahmed, Shaimaa; Bott, Debbie; Gomez, Alvin; Tamblyn, Laura; Rasheed, Adil; Cho, Tiffany; MacPherson, Laura; Sugamori, Kim S.; Yang, Yang; Grant, Denis M.; Cummins, Carolyn L.; Matthews, Jason

2015-01-01

The aryl hydrocarbon receptor (AHR) mediates the toxic effects of the environmental contaminant dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD). Dioxin causes a range of toxic responses, including hepatic damage, steatohepatitis, and a lethal wasting syndrome; however, the mechanisms are still unknown. Here, we show that the loss of TCDD-inducible poly(ADP-ribose) polymerase (Tiparp), an ADP-ribosyltransferase and AHR repressor, increases sensitivity to dioxin-induced toxicity, steatohepatitis, and lethality. Tiparp−/− mice given a single injection of 100 μg/kg dioxin did not survive beyond day 5; all Tiparp+/+ mice survived the 30-day treatment. Dioxin-treated Tiparp−/− mice exhibited increased liver steatosis and hepatotoxicity. Tiparp ADP-ribosylated AHR but not its dimerization partner, the AHR nuclear translocator, and the repressive effects of TIPARP on AHR were reversed by the macrodomain containing mono-ADP-ribosylase MACROD1 but not MACROD2. These results reveal previously unidentified roles for Tiparp, MacroD1, and ADP-ribosylation in AHR-mediated steatohepatitis and lethality in response to dioxin. PMID:25975270

Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP, ADP, and Mg2+

NASA Technical Reports Server (NTRS)

Michailova, Anushka; Saucerman, Jeffrey; Belik, Mary Ellen; McCulloch, Andrew D.

2005-01-01

Changes in cytosolic free Mg(2+) and adenosine nucleotide phosphates affect cardiac excitability and contractility. To investigate how modulation by Mg(2+), ATP, and ADP of K(ATP) and L-type Ca(2+) channels influences excitation-contraction coupling, we incorporated equations for intracellular ATP and MgADP regulation of the K(ATP) current and MgATP regulation of the L-type Ca(2+) current in an ionic-metabolic model of the canine ventricular myocyte. The new model: 1), quantitatively reproduces a dose-response relationship for the effects of changes in ATP on K(ATP) current, 2), simulates effects of ADP in modulating ATP sensitivity of K(ATP) channel, 3), predicts activation of Ca(2+) current during rapid increase in MgATP, and 4), demonstrates that decreased ATP/ADP ratio with normal total Mg(2+) or increased free Mg(2+) with normal ATP and ADP activate K(ATP) current, shorten action potential, and alter ionic currents and intracellular Ca(2+) signals. The model predictions are in agreement with experimental data measured under normal and a variety of pathological conditions.

A new approach of optimal control for a class of continuous-time chaotic systems by an online ADP algorithm

NASA Astrophysics Data System (ADS)

Song, Rui-Zhuo; Xiao, Wen-Dong; Wei, Qing-Lai

2014-05-01

We develop an online adaptive dynamic programming (ADP) based optimal control scheme for continuous-time chaotic systems. The idea is to use the ADP algorithm to obtain the optimal control input that makes the performance index function reach an optimum. The expression of the performance index function for the chaotic system is first presented. The online ADP algorithm is presented to achieve optimal control. In the ADP structure, neural networks are used to construct a critic network and an action network, which can obtain an approximate performance index function and the control input, respectively. It is proven that the critic parameter error dynamics and the closed-loop chaotic systems are uniformly ultimately bounded exponentially. Our simulation results illustrate the performance of the established optimal control method.

ADP-ribosylation of membrane components by pertussis and cholera toxin

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

Ribeiro-Neto, F.A.P.; Mattera, F.; Hildebrandt, J.D.

1985-01-01

Pertussis and cholera toxins are important tools to investigate functional and structural aspects of the stimulatory (N/sub s/) and inhibitory (N/sub i/) regulatory components of adenylyl cyclase. Cholera toxin acts on N/sub s/ by ADP-ribosylating its ..cap alpha../sub s/ subunit; pertussis toxin acts on N/sub i/ by ADP-ribosylating its ..cap alpha..; subunit. By using (/sup 32/P)NAD/sup +/ and determining the transfer of its (/sup 32/P)ADP-ribose moiety to membrane components, it is possible to obtain information on N/sub s/ and N/sub i/. A set of protocols is presented that can be used to study simultaneously and comparatively the susceptibility of N/submore » s/ and N/sub i/ to be ADP-ribosylated by cholera and pertussis toxin.« less

Adrenaline potentiates PI 3-kinase in platelets stimulated with thrombin and SFRLLN: role of secreted ADP.

PubMed

Selheim, F; Frøyset, A K; Strand, I; Vassbotn, F S; Holmsen, H

2000-11-17

Adrenaline significantly potentiated late thrombin- and SFRLLN-induced PtdIns(3,4)P(2) production. Furthermore, the potentiating effect of adrenaline on thrombin-induced PtdIns(3, 4)P(2) production was independent on secreted ADP, whereas, the effect of adrenaline on SFRLLN-induced PtdIns(3,4)P(2) production was completely dependent of secreted ADP. However, the ADP-dependent accumulation of PtdIns(3,4)P(2) was not required for irreversible platelet aggregation induced by SFRLLN in the presence of adrenaline. It is concluded that adrenaline can replace secreted ADP to potentiate PtdIns(3,4)P(2) production in thrombin-stimulated but not in SFRLLN-stimulated platelets, thus demonstrating a qualitative difference between platelet stimulation by thrombin and the thrombin receptor activating peptide SFRLLN.

Substrate specific effects of calcium on metabolism of rat heart mitochondria.

PubMed

Panov, A V; Scaduto, R C

1996-04-01

Oxidative metabolism in the heart is tightly coupled to mechanical work. Because this coupling process is believed to involve Ca2+, the roles of mitochondrial Ca2+ in the regulation of oxidative phosphorylation was studied in isolated rat heart mitochondria. The electrical component of the mitochondrial membrane potential (delta psi) and the redox state of the pyridine nucleotides were determined during the oxidation of various substrates under different metabolic states. In the absence of added adenine nucleotides, the NADP+ redox couple was almost completely reduced, regardless of the specific substrate and the presence of Ca2+, whereas NAD+ couple redox state was highly dependent on the substrate type and the presence of Ca2+. Titration of respiration with ADP, in the presence of excess hexokinase and glucose, showed that both respiration and NAD(P)+ reduction were very sensitive to ADP. The maximal enzyme reaction rate of ADP-stimulated respiration Michaelis constants (Km) for ADP were dependent on the particular substrate employed. delta psi was much less sensitive to ADP. With either alpha-ketoglutarate or glutamate as substrate, Ca2+ significantly increased reduction of NAD(P)+.Ca2+ did not influence NAD(P)+ reduction with either acetylcarnitine or pyruvate as substrate. In the presence of ADP, delta psi was increased by Ca2+ at all metabolic states with glutamate plus malate, 0.5 mM alpha-ketoglutarate plus malate, or pyruvate plus malate as substrates. The data presented support the hypothesis that cardiac respiration is controlled by the availability of both Ca2+ and ADP to mitochondria. The data indicate that an increase in substrate supply to mitochondria can increase mitochondrial respiration at given level of ADP. This effect can be produced by Ca2+ with substrates such as glutamate, which utilize alpha-ketoglutarate dehydrogenase activity for oxidation. Increases in respiration by Ca2+ may mitigate an increase in ADP during periods of increased cardiac work.

Characterization of Recombinant UDP- and ADP-Glucose Pyrophosphorylases and Glycogen Synthase To Elucidate Glucose-1-Phosphate Partitioning into Oligo- and Polysaccharides in Streptomyces coelicolor

PubMed Central

Asención Diez, Matías D.; Peirú, Salvador; Demonte, Ana M.; Gramajo, Hugo

2012-01-01

Streptomyces coelicolor exhibits a major secondary metabolism, deriving important amounts of glucose to synthesize pigmented antibiotics. Understanding the pathways occurring in the bacterium with respect to synthesis of oligo- and polysaccharides is of relevance to determine a plausible scenario for the partitioning of glucose-1-phosphate into different metabolic fates. We report the molecular cloning of the genes coding for UDP- and ADP-glucose pyrophosphorylases as well as for glycogen synthase from genomic DNA of S. coelicolor A3(2). Each gene was heterologously expressed in Escherichia coli cells to produce and purify to electrophoretic homogeneity the respective enzymes. UDP-glucose pyrophosphorylase (UDP-Glc PPase) was characterized as a dimer exhibiting a relatively high Vmax in catalyzing UDP-glucose synthesis (270 units/mg) and with respect to dTDP-glucose (94 units/mg). ADP-glucose pyrophosphorylase (ADP-Glc PPase) was found to be tetrameric in structure and specific in utilizing ATP as a substrate, reaching similar activities in the directions of ADP-glucose synthesis or pyrophosphorolysis (Vmax of 0.15 and 0.27 units/mg, respectively). Glycogen synthase was arranged as a dimer and exhibited specificity in the use of ADP-glucose to elongate α-1,4-glucan chains in the polysaccharide. ADP-Glc PPase was the only of the three enzymes exhibiting sensitivity to allosteric regulation by different metabolites. Mannose-6-phosphate, phosphoenolpyruvate, fructose-6-phosphate, and glucose-6-phosphate behaved as major activators, whereas NADPH was a main inhibitor of ADP-Glc PPase. The results support a metabolic picture where glycogen synthesis occurs via ADP-glucose in S. coelicolor, with the pathway being strictly regulated in connection with other routes involved with oligo- and polysaccharides, as well as with antibiotic synthesis in the bacterium. PMID:22210767

Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets.

PubMed

Bijak, Michal; Szelenberger, Rafal; Dziedzic, Angela; Saluk-Bijak, Joanna

2018-02-10

Adenosine diphosphate (ADP) is the major platelet agonist, which is important in the shape changes, stability, and growth of the thrombus. Platelet activation by ADP is associated with the G protein-coupled receptors P2Y1 and P2Y12. The pharmacologic blockade of the P2Y12 receptor significantly reduces the risk of peripheral artery disease, myocardial infarction, ischemic stroke, and vascular death. Recent studies demonstrated the inhibition of ADP-induced blood platelet activation by three major compounds of the flavonolignans group: silybin, silychristin, and silydianin. For this reason, the aim of the current work was to verify the effects of silybin, silychristin, and silydianin on ADP-induced physiological platelets responses, as well as mechanisms of P2Y12-dependent intracellular signal transduction. We evaluated the effect of tested flavonolignans on ADP-induced blood platelets' aggregation in platelet-rich plasma (PRP) (using light transmission aggregometry), adhesion to fibrinogen (using the static method), and the secretion of PF-4 (using the ELISA method). Additionally, using the double labeled flow cytometry method, we estimated platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation. We demonstrated a dose-dependent reduction of blood platelets' ability to perform ADP-induced aggregation, adhere to fibrinogen, and secrete PF-4 in samples treated with flavonolignans. Additionally, we observed that all of the tested flavonolignans were able to increase VASP phosphorylation in blood platelets samples, which is correlated with P2Y12 receptor inhibition. All of these analyses show that silychristin and silybin have the strongest inhibitory effect on blood platelet activation by ADP, while silydianin also inhibits the ADP pathway, but to a lesser extent. The results obtained in this study clearly demonstrate that silybin, silychristin, and silydianin have inhibitory properties against the P2Y12 receptor and block ADP-induced blood platelet activation.

Evaluation of thrombelastographic platelet-mapping in healthy cats.

PubMed

Blois, Shauna L; Banerjee, Amrita; Wood, R Darren

2012-06-01

Thrombelastography (TEG) permits analysis of clot formation but it is not specific for platelet activity. TEG PlateletMapping (TEG-PM) is a modification of TEG that uses adenosine diphosphate (ADP) and arachidonic acid (AA) as platelet agonists to define the contribution of platelets to clot formation. The objectives of this study were to determine values for TEG-PM in healthy cats and the interassay variation of TEG-PM. TEG-PM analysis was performed on blood specimens collected from 12 healthy cats and was repeated using a second blood specimen collected 2 hours later. Maximum amplitudes generated by thrombin (MA(thrombin)), fibrin (MA(fibrin)), ADP-stimulated platelet activity (MA(ADP)), and AA-stimulated platelet activity (MA(AA)) were recorded. Mean ± SD for MA(thrombin) was 51.1 ± 8.5 mm, for MA(fibrin) was 32.3 ± 17.7 mm, for MA(ADP) was 32.3 ± 15.0 mm, and for MA(AA) was 24.5 ± 12.2 mm. Mean MA(ADP) and MA(fibrin) were not significantly different, whereas mean MA(AA) was significantly lower than mean MA(fibrin). Results from the first and second specimens were not significantly different. Correlation between the first and second specimens was moderate for MA(thrombin), MA(fibrin), and MA(ADP), but was poor for MA(AA). A high degree of variability (coefficient of variation 47.7-60.0%) was observed for MA(fibrin), MA(ADP), and MA(AA). As MA(ADP) and MA(AA) (AA) were the same as or lower than MA(fibrin), a valid baseline to determine platelet-stimulated clot formation could not be established. Considerable interassay variation and wide intervals for MA(fibrin), MA(ADP), and MA(AA) values in this study indicate that TEG-PM should be used cautiously in feline patients. Several preanalytical factors should be examined in further detail. © 2012 American Society for Veterinary Clinical Pathology.

75 FR 29588 - Office of New Reactors: Proposed NUREG-0800; Standard Review Plan Section 13.6.6, Draft Revision...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-26

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0184] Office of New Reactors: Proposed NUREG-0800; Standard Review Plan Section 13.6.6, Draft Revision 0 on Cyber Security Plan AGENCY: Nuclear Regulatory... Plants,'' on a proposed Standard Review Plan (SRP) Section 13.6.6 on ``Cyber Security Plan'' (Agencywide...

Cross-bridge kinetics in the presence of MgADP investigated by photolysis of caged ATP in rabbit psoas muscle fibres.

PubMed Central

Dantzig, J A; Hibberd, M G; Trentham, D R; Goldman, Y E

1991-01-01

1. The interaction between MgADP and rigor cross-bridges in glycerol-extracted single fibres from rabbit psoas muscle has been investigated using laser pulse photolysis of caged ATP (P3-1(2-nitrophenyl)ethyladenosine 5'-triphosphate) in the presence of MgADP and following small length changes applied to the rigor fibre. 2. Addition of 465 microM-MgADP to a rigor fibre caused rigor tension to decrease by 15.3 +/- 0.7% (S.E.M., n = 24 trials in thirteen fibres). The half-saturation value for this tension reduction was 18 +/- 4 microM (n = 23, thirteen fibres). 3. Relaxation from rigor by photolysis of caged ATP in the absence of Ca2+ was markedly slowed by inclusion of 20 microM-2 mM-MgADP in the photolysis medium. 4. Four phases of tension relaxation occurred with MgADP in the medium: at, a quick partial relaxation (in pre-stretch fibres); bt, a slowing of relaxation or a rise in tension for 50-100 ms; ct, a sudden acceleration of relaxation; and dt, a final, nearly exponential relaxation. 5. Experiments at varied MgATP and MgADP concentrations suggested that phase at is due to MgATP binding to nucleotide-free cross-bridges. 6. Phase bt was abbreviated by including 1-20 mM-orthophosphate (Pi) in the photolysis medium, or by applying quick stretches before photolysis or during phase bt. These results suggest that phases bt and ct are complex processes involving ADP dissociation, cross-bridge reattachment and co-operative detachment involving filament sliding and the Ca(2+)-regulatory system. 7. Stretching relaxed muscle fibres to 3.2-3.4 microns striation spacing followed by ATP removal and release of the rigor fibre until tension fell below the relaxed level allowed investigation of the strain dependence of relaxation in the regions of negative cross-bridge strain. In the presence of 50 microM-2 mM-MgADP and either 10 mM-Pi or 20 mM-2,3-butanedione monoxime, relaxation following photolysis of caged ATP was 6- to 8-fold faster for negatively strained cross-bridges than for positively strained ones. This marked strain dependence of cross-bridge detachment is predicted from the model of A. F. Huxley (1957). 8. In the presence of Ca2+, activation of contraction following photolysis of caged ATP was slowed by inclusion of 20-500 microM-MgADP in the medium. An initial decrease in tension related to cross-bridge detachment by MgATP was markedly suppressed in the presence of MgADP. 9. Ten millimolar Pi partly suppressed active tension generation in the presence of MgADP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1886072

29 CFR 2530.201-2 - Plans covered by part 2530.

Code of Federal Regulations, 2010 CFR

2010-07-01

... employee welfare benefit plan as defined in section 3(1) of the Act and § 2510.3-1; (b) A plan which is... Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR MINIMUM STANDARDS FOR EMPLOYEE PENSION BENEFIT PLANS UNDER THE EMPLOYEE RETIREMENT INCOME SECURITY...

Hazardous material transportation safety and security field operational test final detailed test plans : executive summary

DOT National Transportation Integrated Search

2003-09-16

The objective of this Hazardous Material (HazMat) Transportation Safety and Security Field Operational Test (FOT) Final Detailed Test Plans evaluation is to measure the impact of technology solutions on the safety, security, and operational efficienc...

17 CFR 200.552 - NEPA planning.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false NEPA planning. 200.552 Section 200.552 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION ORGANIZATION; CONDUCT AND ETHICS; AND INFORMATION AND REQUESTS Regulations Pertaining to the Protection of the Environment...

Comparison of Methods for Assessing Body Composition Changes during Weight Loss.

ERIC Educational Resources Information Center

Weyers, Anna M.; Mazzetti, Scott A.; Love, Dawn M.; Gomez, Ana L.; Kraemer, William J.; Volek, Jeff S.

2002-01-01

Investigated whether dual-energy x-ray absorptiometry (DXA) and air displacement plethysmography (ADP) would detect similar changes in body composition after moderate weight loss. Twenty adults had their body composition measured using DXA and ADP before and after an 8-week weight loss program. Overall, both DXA and ADP detected similar changes in…

Information Fusion for Situational Awareness

DTIC Science & Technology

2003-01-01

UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP021704 TITLE: Information Fusion for Situational Awareness DISTRIBUTION...component part numbers comprise the compilation report: ADP021634 thru ADP021736 UNCLASSIFIED Information Fusion for Situational Awareness Dr. John...Situation Assessment, or level 2 be applied to address Situational Awareness - the processing, the knowledge of objects, their goal of this paper

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

None

This Department of Energy’s (DOE) National Nuclear Security Administration (NNSA) Fiscal Year Stockpile Stewardship and Management Plan (SSMP) is a key planning document for the nuclear security enterprise.

Automated Support for Rapid Coordination of Joint UUV Operation

DTIC Science & Technology

2015-03-01

automata , dead-reckoning, static plan, nmtime plan, rapid deployment, GPS 17. SECURITY CLASSIFICATION OF REPORT Unclassified 18. SECURITY...STATE MACHINES, MOORE AUTOMATA ..........................................9 A. MOORE AUTOMATA ...9 B. UUV PLANS AS MOORE AUTOMATA ...................................................11 C. SAMPLING RATE

Comparison of methods to assess change in children’s body composition123

PubMed Central

Elberg, Jane; McDuffie, Jennifer R; Sebring, Nancy G; Salaita, Christine; Keil, Margaret; Robotham, Delphine; Reynolds, James C; Yanovski, Jack A

2008-01-01

Background Little is known about how simpler and more available methods to measure change in body fatness compare with criterion methods such as dual-energy X-ray absorptiometry (DXA) in children. Objective Our objective was to determine the ability of air-displacement plethysmography (ADP) and formulas based on triceps skinfold thickness (TSF) and bioelectrical impedance analysis (BIA) to estimate changes in body fat over time in children. Design Eighty-six nonoverweight and overweight boys (n = 34) and girls (n = 52) with an average age of 11.0 ± 2.4 y underwent ADP, TSF measurement, BIA, and DXA to estimate body fatness at baseline and 1 ± 0.3 y later. Recent equations were used to estimate percentage body fat by TSF measurement (Dezenberg equation) and by BIA (Suprasongsin and Lewy equations). Percentage body fat estimates by ADP, TSF measurement, and BIA were compared with those by DXA. Results All methods were highly correlated with DXA (P < 0.001). No mean bias for estimates of percentage body fat change was found for ADP (Siri equation) compared with DXA for all subjects examined together, and agreement between body fat estimation by ADP and DXA did not vary with race or sex. Magnitude bias was present for ADP relative to DXA (P < 0.01). Estimates of change in percentage body fat were systematically overestimated by BIA equations (1.37 ± 6.98%; P < 0.001). TSF accounted for only 13% of the variance in percentage body fat change. Conclusion Compared with DXA, there appears to be no noninvasive and simple method to measure changes in children’s percentage body fat accurately and precisely, but ADP performed better than did TSF or BIA. ADP could prove useful for measuring changes in adiposity in children. PMID:15213029

Interaction of clothing and body mass index affects validity of air-displacement plethysmography in adults.

PubMed

Shafer, Kimberly J; Siders, William A; Johnson, LuAnn K; Lukaski, Henry C

2008-02-01

We determined the effect of clothing type on the validity of air-displacement plethysmography (ADP) to estimate percentage of body fat (%BF) and ascertain if these effects differ by body mass index (BMI). The %BF by dual x-ray absorptiometry (DXA) and %BF, density, and body volume by ADP were assessed in 132 healthy adults classified by normal (N; 18.5-24.9 kg/m2), overweight (OW; 25-29.9 kg/m2), and obese (OB; 30-39.9 kg/m2) BMIs. Compared with DXA, ADP underestimated (P < 0.0001) %BF from scrubs (SC) and t-shirt/shorts (TS) in N (11.4%; 8.6%) and OW (6.8%; 4.9%) BMI groups, respectively. ADP compared with DXA overestimated (P < 0.0006) %BF in the OW group (1.2%), but underestimated (P < 0.0001) it in the N group (2.4%). ADP also overestimated (P < 0.006) %BF in the OB group wearing spandex (SP; 4.8%), but not in those wearing SC (0.7%; P = 0.10) and TS (0.5%; P = 0.22) versus DXA. All three clothing types showed significant error in estimating %BF with ADP compared with DXA in N and OW BMI. Use of spandex provided the least error and is the preferred attire to obtain valid body composition results when testing N and OW subjects. However, SP provided the greatest error in the OB group. Error in ADP %BF in OB was minimal in SC and TS and similar to the within-subject variability in %BF estimates with ADP. Thus, TS and SC are acceptable alternatives to SP in adults with excess body weight.

Interaction of Prevotella intermedia Strain 17 Leucine-Rich Repeat Domain Protein AdpF with Eukaryotic Cells Promotes Bacterial Internalization

PubMed Central

Sengupta, Dipanwita; Kang, Dae-Joong; Anaya-Bergman, Cecilia; Wyant, Tiana; Ghosh, Arnab K.; Miyazaki, Hiroshi

2014-01-01

Prevotella intermedia is an oral bacterium implicated in a variety of oral diseases. Although internalization of this bacterium by nonphagocytic host cells is well established, the molecular players mediating the process are not well known. Here, the properties of a leucine-rich repeat (LRR) domain protein, designated AdpF, are described. This protein contains a leucine-rich region composed of 663 amino acid residues, and molecular modeling shows that it folds into a classical curved solenoid structure. The cell surface localization of recombinant AdpF (rAdpF) was confirmed by electron and confocal microscopy analyses. The recombinant form of this protein bound fibronectin in a dose-dependent manner. Furthermore, the protein was internalized by host cells, with the majority of the process accomplished within 30 min. The internalization of rAdpF was inhibited by nystatin, cytochalasin, latrunculin, nocodazole, and wortmannin, indicating that microtubules, microfilaments, and signal transduction are required for the invasion. It is noteworthy that preincubation of eukaryotic cells with AdpF increased P. intermedia 17 internalization by 5- and 10-fold for HeLa and NIH 3T3 fibroblast cell lines, respectively. The addition of the rAdpF protein was also very effective in inducing bacterial internalization into the oral epithelial cell line HN4, as well as into primary cells, including human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs). Finally, cells exposed to P. intermedia 17 internalized the bacteria more readily upon reinfection. Taken together, our data demonstrate that rAdpF plays a role in the internalization of P. intermedia 17 by a variety of host cells. PMID:24711565

Interaction of Prevotella intermedia strain 17 leucine-rich repeat domain protein AdpF with eukaryotic cells promotes bacterial internalization.

PubMed

Sengupta, Dipanwita; Kang, Dae-Joong; Anaya-Bergman, Cecilia; Wyant, Tiana; Ghosh, Arnab K; Miyazaki, Hiroshi; Lewis, Janina P

2014-06-01

Prevotella intermedia is an oral bacterium implicated in a variety of oral diseases. Although internalization of this bacterium by nonphagocytic host cells is well established, the molecular players mediating the process are not well known. Here, the properties of a leucine-rich repeat (LRR) domain protein, designated AdpF, are described. This protein contains a leucine-rich region composed of 663 amino acid residues, and molecular modeling shows that it folds into a classical curved solenoid structure. The cell surface localization of recombinant AdpF (rAdpF) was confirmed by electron and confocal microscopy analyses. The recombinant form of this protein bound fibronectin in a dose-dependent manner. Furthermore, the protein was internalized by host cells, with the majority of the process accomplished within 30 min. The internalization of rAdpF was inhibited by nystatin, cytochalasin, latrunculin, nocodazole, and wortmannin, indicating that microtubules, microfilaments, and signal transduction are required for the invasion. It is noteworthy that preincubation of eukaryotic cells with AdpF increased P. intermedia 17 internalization by 5- and 10-fold for HeLa and NIH 3T3 fibroblast cell lines, respectively. The addition of the rAdpF protein was also very effective in inducing bacterial internalization into the oral epithelial cell line HN4, as well as into primary cells, including human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs). Finally, cells exposed to P. intermedia 17 internalized the bacteria more readily upon reinfection. Taken together, our data demonstrate that rAdpF plays a role in the internalization of P. intermedia 17 by a variety of host cells.

The regulatory properties of Rubisco activase differ among species and affect photosynthetic induction during light transitions.

PubMed

Carmo-Silva, A Elizabete; Salvucci, Michael E

2013-04-01

Rubisco's catalytic chaperone, Rubisco activase (Rca), uses the energy from ATP hydrolysis to restore catalytic competence to Rubisco. In Arabidopsis (Arabidopsis thaliana), inhibition of Rca activity by ADP is fine tuned by redox regulation of the α-isoform. To elucidate the mechanism for Rca regulation in species containing only the redox-insensitive β-isoform, the response of activity to ADP was characterized for different Rca forms. When assayed in leaf extracts, Rubisco activation was significantly inhibited by physiological ratios of ADP to ATP in species containing both α-Rca and β-Rca (Arabidopsis and camelina [Camelina sativa]) or just the β-Rca (tobacco [Nicotiana tabacum]). However, Rca activity was insensitive to ADP inhibition in an Arabidopsis transformant, rwt43, which expresses only Arabidopsis β-Rca, although not in a transformant of Arabidopsis that expresses a tobacco-like β-Rca. ATP hydrolysis by recombinant Arabidopsis β-Rca was much less sensitive to inhibition by ADP than recombinant tobacco β-Rca. Mutation of 17 amino acids in the tobacco β-Rca to the corresponding Arabidopsis residues reduced ADP sensitivity. In planta, Rubisco deactivated at low irradiance except in the Arabidopsis rwt43 transformant containing an ADP-insensitive Rca. Induction of CO2 assimilation after transition from low to high irradiance was much more rapid in the rwt43 transformant compared with plants containing ADP-sensitive Rca forms. The faster rate of photosynthetic induction and a greater enhancement of growth under a fluctuating light regime by the rwt43 transformant compared with wild-type Arabidopsis suggests that manipulation of Rca regulation might provide a strategy for enhancing photosynthetic performance in certain variable light environments.

Redesign of Schistosoma mansoni NAD+ catabolizing enzyme : the active site H103W mutation restores ADP-ribosyl cyclase activity†

PubMed Central

Kuhn, Isabelle; Kellenberger, Esther; Rognan, Didier; Lund, Frances E.; Muller-Steffner, Hélène; Schuber, Francis

2008-01-01

Schistosoma mansoni NAD(P)+ catabolizing enzyme (SmNACE) is a new member of the ADP-ribosyl cyclase family. In contrast to all the other enzymes which are involved in the production of metabolites that elicit Ca2+ mobilization, SmNACE is virtually unable to transform NAD+ into the second messenger cyclic ADP-ribose (cADPR). Sequence alignments revealed that one of four conserved residues within the active site of these enzymes was replaced in SmNACE by a histidine (His103) instead of the highly conserved tryptophan. To find out whether the inability of SmNACE to catalyze the canonical ADP-ribosyl cyclase reaction is linked to this change we have replaced His103 with a tryptophan. The H103W mutation in SmNACE was indeed found to restore ADP-ribosyl cyclase activity as cADPR amounts for 7% of the reaction products, i.e., a value larger than observed for other members of this family such as CD38. Introduction of a Trp103 residue provides some of the binding characteristics of mammalian ADP-ribosyl cyclases such as increased affinity for Cibacron blue and slow-binding inhibition by araF-NAD+. Homology modeling of wild-type and H103W mutant three-dimensional structures, and docking of substrates within the active sites, provide new insight into the catalytic mechanism of SmNACE. Both residue side chains share similar roles in the nicotinamide-ribose bond cleavage step leading to an E.ADP-ribosyl reaction intermediate. They diverge however in the evolution of this intermediate; His103 provides a more polar environment favoring the accessibility to water and hydrolysis leading to ADP-ribose at the expense of the intramolecular cyclization pathway resulting in cADPR. PMID:17002287

The affinity of a major Ca2+ binding site on GRP78 is differentially enhanced by ADP and ATP.

PubMed

Lamb, Heather K; Mee, Christopher; Xu, Weiming; Liu, Lizhi; Blond, Sylvie; Cooper, Alan; Charles, Ian G; Hawkins, Alastair R

2006-03-31

GRP78 is a major protein regulated by the mammalian endoplasmic reticulum stress response, and up-regulation has been shown to be important in protecting cells from challenge with cytotoxic agents. GRP78 has ATPase activity, acts as a chaperone, and interacts specifically with other proteins, such as caspases, as part of a mechanism regulating apoptosis. GRP78 is also reported to have a possible role as a Ca2+ storage protein. In order to understand the potential biological effects of Ca2+ and ATP/ADP binding on the biology of GRP78, we have determined its ligand binding properties. We show here for the first time that GRP78 can bind Ca2+, ATP, and ADP, each with a 1:1 stoichiometry, and that the binding of cation and nucleotide is cooperative. These observations do not support the hypothesis that GRP78 is a dynamic Ca2+ storage protein. Furthermore, we demonstrate that whereas Mg2+ enhances GRP78 binding to ADP and ATP to the same extent, Ca2+ shows a differential enhancement. In the presence of Ca2+, the KD for ATP is lowered approximately 11-fold, and the KD for ADP is lowered around 930-fold. The KD for Ca2+ is lowered approximately 40-fold in the presence of ATP and around 880-fold with ADP. These findings may explain the biological requirement for a nucleotide exchange factor to remove ADP from GRP78. Taken together, our data suggest that the Ca2+-binding property of GRP78 may be part of a signal transduction pathway that modulates complex interactions between GRP78, ATP/ADP, secretory proteins, and caspases, and this ultimately has important consequences for cell viability.

PARPs and ADP-Ribosylation: 50 Years … and Counting.

PubMed

Kraus, W Lee

2015-06-18

Over 50 years ago, the discovery of poly(ADP-ribose) (PAR) set a new field of science in motion-the field of poly(ADP-ribosyl) transferases (PARPs) and ADP-ribosylation. The field is still flourishing today. The diversity of biological processes now known to require PARPs and ADP-ribosylation was practically unimaginable even two decades ago. From an initial focus on DNA damage detection and repair in response to genotoxic stresses, the field has expanded to include the regulation of chromatin structure, gene expression, and RNA processing in a wide range of biological systems, including reproduction, development, aging, stem cells, inflammation, metabolism, and cancer. This special focus issue of Molecular Cell includes a collection of three Reviews, three Perspectives, and a SnapShot, which together summarize the current state of the field and suggest where it may be headed. Copyright © 2015 Elsevier Inc. All rights reserved.

Adaptive dynamic programming for finite-horizon optimal control of discrete-time nonlinear systems with ε-error bound.

PubMed

Wang, Fei-Yue; Jin, Ning; Liu, Derong; Wei, Qinglai

2011-01-01

In this paper, we study the finite-horizon optimal control problem for discrete-time nonlinear systems using the adaptive dynamic programming (ADP) approach. The idea is to use an iterative ADP algorithm to obtain the optimal control law which makes the performance index function close to the greatest lower bound of all performance indices within an ε-error bound. The optimal number of control steps can also be obtained by the proposed ADP algorithms. A convergence analysis of the proposed ADP algorithms in terms of performance index function and control policy is made. In order to facilitate the implementation of the iterative ADP algorithms, neural networks are used for approximating the performance index function, computing the optimal control policy, and modeling the nonlinear system. Finally, two simulation examples are employed to illustrate the applicability of the proposed method.

Planning high security/high profile events.

PubMed

McCafferty, Mike

2013-01-01

The author who has lead in the planning and implementation of some of the most notorious trials and events, both in Canada and internationally, describes how such these experiences could be applied to focused high security planning in the health care industry.

Pratt & Whitney Advanced Ducted Propulsor (ADP) Engine Test in 40x80ft w.t.: Engineers Peter

NASA Technical Reports Server (NTRS)

1993-01-01

Pratt & Whitney Advanced Ducted Propulsor (ADP) Engine Test in 40x80ft w.t.: Engineers Peter Zell (left) and Dr Clifton Horne (right) are shown preparing a laser light sheet for a flow visualization test. Shown standing in the nacelle of the ADP is John Girvin, senior test engineer for Pratt & Whitney.

Pratt & Whitney Advanced Ducted Propulsor (ADP) Engine Test in 40x80ft w.t.: Engineers Peter

NASA Technical Reports Server (NTRS)

1993-01-01

Pratt & Whitney Advanced Ducted Propulsor (ADP) Engine Test in 40x80ft w.t.: Engineers Peter Zell (left) and Dr Clifton Horne (right) are shown preparing for a laser light sheet for a flow visualization test. Shown standing in the nacelle of the ADP is John Girvin, senior test engineer for Pratt & Whitney.

Social Security Administration

MedlinePlus

... Plan Costs my Social Security Check out your Social Security Statement , change your address & manage your benefits online today. Social Security Number Your Social Security number remains your ...

Inhibiting poly(ADP-ribose) polymerase: a potential therapy against oligodendrocyte death

PubMed Central

Veto, Sara; Acs, Peter; Bauer, Jan; Lassmann, Hans; Berente, Zoltan; Setalo, Gyorgy; Borgulya, Gabor; Sumegi, Balazs; Komoly, Samuel; Gallyas, Ferenc; Illes, Zsolt

2010-01-01

Oligodendrocyte loss and demyelination are major pathological hallmarks of multiple sclerosis. In pattern III lesions, inflammation is minor in the early stages, and oligodendrocyte apoptosis prevails, which appears to be mediated at least in part through mitochondrial injury. Here, we demonstrate poly(ADP-ribose) polymerase activation and apoptosis inducing factor nuclear translocation within apoptotic oligodendrocytes in such multiple sclerosis lesions. The same morphological and molecular pathology was observed in an experimental model of primary demyelination, induced by the mitochondrial toxin cuprizone. Inhibition of poly(ADP-ribose) polymerase in this model attenuated oligodendrocyte depletion and decreased demyelination. Poly(ADP-ribose) polymerase inhibition suppressed c-Jun N-terminal kinase and p38 mitogen-activated protein kinase phosphorylation, increased the activation of the cytoprotective phosphatidylinositol-3 kinase-Akt pathway and prevented caspase-independent apoptosis inducing factor-mediated apoptosis. Our data indicate that poly(ADP-ribose) polymerase activation plays a crucial role in the pathogenesis of pattern III multiple sclerosis lesions. Since poly(ADP-ribose) polymerase inhibition was also effective in the inflammatory model of multiple sclerosis, it may target all subtypes of multiple sclerosis, either by preventing oligodendrocyte death or attenuating inflammation. PMID:20157013

Study of linear optical parameters of sodium sulphide nano-particles added ADP crystals

NASA Astrophysics Data System (ADS)

Kochuparampil, A. P.; Joshi, J. H.; Dixit, K. P.; Jethva, H. O.; Joshi, M. J.

2017-05-01

Ammonium Dihydrogen Phosphate (ADP) is one of the nonlinear optical crystals. It is having various applications like optical mixing, electro-optical modulator, harmonic generators, etc. Chalcogenide compounds are poorly soluble in water and difficult to add in the water soluble ADP crystals. The solubility of Chalcogenide compounds can be increased by synthesizing the nano-structured samples with suitable capping agent. In the present study sodium sulphide was added in to ADP to modify its linear optical parameters. Sodium sulphide nano particles were synthesized by co-precipitation technique using Ethylene diamine as capping agent followed by microwave irradiation. The powder XRD confirmed the nano-structured nature of sodium sulphide nano particles. The solubility of nanoparticles of sodium sulphide increased significantly in water compared to the bulk. Pure and Na2S added ADP crystals were grown by slow solvent evaporation method at room temperature. The presence of sodium in ADP was confirmed by AAS. The UV-Vis spectra were recorded for all crystals. Various optical parameters like, transmittance, energy band gap, extinction coefficient, refractive index, optical conductivity, etc. were evaluated. The electronic polarizibility of pure and doped crystals calculated from energy band gap. The effect of doping concentration was found on various parameters.

Reprogramming cellular events by poly(ADP-ribose)-binding proteins

PubMed Central

Pic, Émilie; Ethier, Chantal; Dawson, Ted M.; Dawson, Valina L.; Masson, Jean-Yves; Poirier, Guy G.; Gagné, Jean-Philippe

2013-01-01

Poly(ADP-ribosyl)ation is a posttranslational modification catalyzed by the poly(ADP-ribose) polymerases (PARPs). These enzymes covalently modify glutamic, aspartic and lysine amino acid side chains of acceptor proteins by the sequential addition of ADP-ribose (ADPr) units. The poly(ADP-ribose) (pADPr) polymers formed alter the physico-chemical characteristics of the substrate with functional consequences on its biological activities. Recently, non-covalent binding to pADPr has emerged as a key mechanism to modulate and coordinate several intracellular pathways including the DNA damage response, protein stability and cell death. In this review, we describe the basis of non-covalent binding to pADPr that has led to the emerging concept of pADPr-responsive signaling pathways. This review emphasizes the structural elements and the modular strategies developed by pADPr-binding proteins to exert a fine-tuned control of a variety of pathways. Poly(ADP-ribosyl)ation reactions are highly regulated processes, both spatially and temporally, for which at least four specialized pADPr-binding modules accommodate different pADPr structures and reprogram protein functions. In this review, we highlight the role of well-characterized and newly discovered pADPr-binding modules in a diverse set of physiological functions. PMID:23268355

The characteristics of the (alpha V371C)3(beta R337C)3 gamma double mutant subcomplex of the TF1-ATPase indicate that the catalytic site at the alpha TP-beta TP interface with bound MgADP in crystal structures of MF1 represents a catalytic site containing inhibitory MgADP.

PubMed

Bandyopadhyay, Sanjay; Muneyuki, Eiro; Allison, William S

2005-02-22

In the MF(1) crystal structure with the MgADP-fluoroaluminate complex bound to two catalytic sites [Menz, R. I., Walker, J. E., and Leslie, A. G. W. (2001) Cell 106, 331-341], the guanidinium of betaR(337) is within 2.9 A of the alpha-oxygen of alphaS(370) and 3.7 A of a methyl group of alphaV(371) at the alpha(E)-beta(HC) interface. To examine the functional role of this contact, the (alphaV(371)C)(3)(betaR(337)C)(3)gamma subcomplex of the TF(1)-ATPase was prepared and characterized. Steady state ATPase activity of the reduced double-mutant is 30% of that of the wild type. Inactivation of the double mutant containing empty catalytic sites or MgADP bound to one catalytic site with CuCl(2) cross-linked two alpha-beta pairs, whereas a single alpha-beta pair cross-linked when at least two catalytic sites contained MgADP. The reduced double mutant hydrolyzed substoichiometric ATP 100-fold more rapidly than the enzyme containing two cross-linked alpha-beta pairs. Addition of AlCl(3) and NaF to the reduced double mutant after incubation with stoichiometric MgADP or 200 microM MgADP irreversibly inactivated the steady state ATPase activity with rate constants of 1.5 x10(-2) and 4.1 x 10(-2) min(-1), respectively. In contrast, addition of AlCl(3) and NaF to the cross-linked enzyme after incubation with stoichiometric or 200 microM MgADP irreversibly inactivated ATPase activity with a common rate constant of approximately 10(-4) min(-1). Correlation of these results with crystal structures of MF(1) suggests that the catalytic site at the alpha(TP)-beta(TP) interface is loaded first upon addition of nucleotides to nucleotide-depleted F(1)-ATPases and that the catalytic site at the alpha(TP)-beta(TP) interface with bound MgADP in crystal structures represents a catalytic site containing inhibitory MgADP.

49 CFR 15.7 - Covered persons.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Office of the Secretary of Transportation PROTECTION OF SENSITIVE SECURITY INFORMATION § 15.7 Covered... owners, charterers, and operators, required to have a security plan under Federal or International law. (d) Each owner or operator of a maritime facility required to have a security plan under the Maritime...

49 CFR 15.7 - Covered persons.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Office of the Secretary of Transportation PROTECTION OF SENSITIVE SECURITY INFORMATION § 15.7 Covered... owners, charterers, and operators, required to have a security plan under Federal or International law. (d) Each owner or operator of a maritime facility required to have a security plan under the Maritime...

49 CFR 15.7 - Covered persons.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Office of the Secretary of Transportation PROTECTION OF SENSITIVE SECURITY INFORMATION § 15.7 Covered... owners, charterers, and operators, required to have a security plan under Federal or International law. (d) Each owner or operator of a maritime facility required to have a security plan under the Maritime...

49 CFR 15.7 - Covered persons.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Office of the Secretary of Transportation PROTECTION OF SENSITIVE SECURITY INFORMATION § 15.7 Covered... owners, charterers, and operators, required to have a security plan under Federal or International law. (d) Each owner or operator of a maritime facility required to have a security plan under the Maritime...

49 CFR 15.7 - Covered persons.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Office of the Secretary of Transportation PROTECTION OF SENSITIVE SECURITY INFORMATION § 15.7 Covered... owners, charterers, and operators, required to have a security plan under Federal or International law. (d) Each owner or operator of a maritime facility required to have a security plan under the Maritime...

Focusing America’s National Powers

DTIC Science & Technology

2006-04-14

governments with market economies. 15. SUBJECT TERMS National Security, National Powers, Sources of Power, National Security Council, National Security... Strategy , Six-phased Campaign Plan, JIACG, DIME 16. SECURITY CLASSIFICATION OF: Unclassified 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME...satisfaction of the requirements of a Master of Science Degree in Joint Campaign Planning and Strategy . The contents of this paper reflect my own

Interaction of promethazine and adiphenine to human hemoglobin: A comparative spectroscopic and computational analysis

NASA Astrophysics Data System (ADS)

Maurya, Neha; ud din Parray, Mehraj; Maurya, Jitendra Kumar; Kumar, Amit; Patel, Rajan

2018-06-01

The binding nature of amphiphilic drugs viz. promethazine hydrochloride (PMT) and adiphenine hydrochloride (ADP), with human hemoglobin (Hb) was unraveled by fluorescence, absorbance, time resolved fluorescence, fluorescence resonance energy transfer (FRET) and circular dichroism (CD) spectral techniques in combination with molecular docking and molecular dynamic simulation methods. The steady state fluorescence spectra indicated that both PMT and ADP quenches the fluorescence of Hb through static quenching mechanism which was further confirmed by time resolved fluorescence spectra. The UV-Vis spectroscopy suggested ground state complex formation. The activation energy (Ea) was observed more in the case of Hb-ADP than Hb-PMT interaction system. The FRET result indicates the high probability of energy transfer from β Trp37 residue of Hb to the PMT (r = 2.02 nm) and ADP (r = 2.33 nm). The thermodynamic data reveal that binding of PMT with Hb are exothermic in nature involving hydrogen bonding and van der Waal interaction whereas in the case of ADP hydrophobic forces play the major role and binding process is endothermic in nature. The CD results show that both PMT and ADP, induced secondary structural changes of Hb and unfold the protein by losing a large helical content while the effect is more pronounced with ADP. Additionally, we also utilized computational approaches for deep insight into the binding of these drugs with Hb and the results are well matched with our experimental results.

Specific cardiolipin binding interferes with labeling of sulfhydryl residues in the adenosine diphosphate/adenosine triphosphate carrier protein from beef heart mitochondria.

PubMed

Beyer, K; Nuscher, B

1996-12-10

The interaction of cardiolipin with the isolated ADP/ATP carrier protein from beef heart mitochondria has been studied by means of the unmasking of a single cysteinyl residue, Cys56, which accompanies the conformational transition of the protein [Leblanc, P., & Clauser, H, (1972) FEBS Lett. 23, 107-113]. The unmasking was monitored by using the static fluorescence of the sulfhydryl reagent N-(1-pyrenyl)maleimide (PYM). The rate of PYM binding that was observed after initiation of the conformational transition by ADP was drastically reduced in the presence of cardiolipin (CL). Phospholipids other than CL were much less effective. It can be shown that the conformational transition and the binding reaction are both affected by CL, although to varying extents. An enhancement of the rate of the ADP-dependent PYM binding was observed upon digestion of the protein bound phospholipid by phospholipase A2. The phospholipase treatment also led to an increased ADP-independent PYM binding, thus indicating that the ADP control of the carrier transition was gradually lost. The ADP control could be fully restored through the addition of CL, provided that the phospholipase incubation had been terminated after approximately 1 h. These results will be discussed in relation to an earlier report of tight cardiolipin binding [Beyer, K., & Klingenberg, M. (1985) Biochemistry 24, 3821-3826] and to current structural models of the ADP/ATP carrier protein.

Origin recognition is the predominant role for DnaA-ATP in initiation of chromosome replication.

PubMed

Grimwade, Julia E; Rozgaja, Tania A; Gupta, Rajat; Dyson, Kyle; Rao, Prassanna; Leonard, Alan C

2018-05-25

In all cells, initiation of chromosome replication depends on the activity of AAA+ initiator proteins that form complexes with replication origin DNA. In bacteria, the conserved, adenosine triphosphate (ATP)-regulated initiator protein, DnaA, forms a complex with the origin, oriC, that mediates DNA strand separation and recruitment of replication machinery. Complex assembly and origin activation requires DnaA-ATP, which differs from DnaA-ADP in its ability to cooperatively bind specific low affinity sites and also to oligomerize into helical filaments. The degree to which each of these activities contributes to the DnaA-ATP requirement for initiation is not known. In this study, we compared the DnaA-ATP dependence of initiation from wild-type Escherichia coli oriC and a synthetic origin (oriCallADP), whose multiple low affinity DnaA sites bind DnaA-ATP and DnaA-ADP similarly. OriCallADP was fully occupied and unwound by DnaA-ADP in vitro, and, in vivo, oriCallADP suppressed lethality of DnaA mutants defective in ATP binding and ATP-specific oligomerization. However, loss of preferential DnaA-ATP binding caused over-initiation and increased sensitivity to replicative stress. The findings indicate both DnaA-ATP and DnaA-ADP can perform most of the mechanical functions needed for origin activation, and suggest that a key reason for ATP-regulation of DnaA is to control replication initiation frequency.

Augmentation of poly(ADP-ribose) polymerase-dependent neuronal cell death by acidosis.

PubMed

Zhang, Jian; Li, Xiaoling; Kwansa, Herman; Kim, Yun Tai; Yi, Liye; Hong, Gina; Andrabi, Shaida A; Dawson, Valina L; Dawson, Ted M; Koehler, Raymond C; Yang, Zeng-Jin

2017-06-01

Tissue acidosis is a key component of cerebral ischemic injury, but its influence on cell death signaling pathways is not well defined. One such pathway is parthanatos, in which oxidative damage to DNA results in activation of poly(ADP-ribose) polymerase and generation of poly(ADP-ribose) polymers that trigger release of mitochondrial apoptosis-inducing factor. In primary neuronal cultures, we first investigated whether acidosis per sé is capable of augmenting parthanatos signaling initiated pharmacologically with the DNA alkylating agent, N-methyl- N'-nitro- N-nitrosoguanidine. Exposure of neurons to medium at pH 6.2 for 4 h after N-methyl- N'-nitro- N-nitrosoguanidine washout increased intracellular calcium and augmented the N-methyl- N'-nitro- N-nitrosoguanidine-evoked increase in poly(ADP-ribose) polymers, nuclear apoptosis-inducing factor , and cell death. The augmented nuclear apoptosis-inducing factor and cell death were blocked by the acid-sensitive ion channel-1a inhibitor, psalmotoxin. In vivo, acute hyperglycemia during transient focal cerebral ischemia augmented tissue acidosis, poly(ADP-ribose) polymers formation, and nuclear apoptosis-inducing factor , which was attenuated by a poly(ADP-ribose) polymerase inhibitor. Infarct volume from hyperglycemic ischemia was decreased in poly(ADP-ribose) polymerase 1-null mice. Collectively, these results demonstrate that acidosis can directly amplify neuronal parthanatos in the absence of ischemia through acid-sensitive ion channel-1a . The results further support parthanatos as one of the mechanisms by which ischemia-associated tissue acidosis augments cell death.

Interaction of promethazine and adiphenine to human hemoglobin: A comparative spectroscopic and computational analysis.

PubMed

Maurya, Neha; Ud Din Parray, Mehraj; Maurya, Jitendra Kumar; Kumar, Amit; Patel, Rajan

2018-06-15

The binding nature of amphiphilic drugs viz. promethazine hydrochloride (PMT) and adiphenine hydrochloride (ADP), with human hemoglobin (Hb) was unraveled by fluorescence, absorbance, time resolved fluorescence, fluorescence resonance energy transfer (FRET) and circular dichroism (CD) spectral techniques in combination with molecular docking and molecular dynamic simulation methods. The steady state fluorescence spectra indicated that both PMT and ADP quenches the fluorescence of Hb through static quenching mechanism which was further confirmed by time resolved fluorescence spectra. The UV-Vis spectroscopy suggested ground state complex formation. The activation energy (E a ) was observed more in the case of Hb-ADP than Hb-PMT interaction system. The FRET result indicates the high probability of energy transfer from β Trp37 residue of Hb to the PMT (r=2.02nm) and ADP (r=2.33nm). The thermodynamic data reveal that binding of PMT with Hb are exothermic in nature involving hydrogen bonding and van der Waal interaction whereas in the case of ADP hydrophobic forces play the major role and binding process is endothermic in nature. The CD results show that both PMT and ADP, induced secondary structural changes of Hb and unfold the protein by losing a large helical content while the effect is more pronounced with ADP. Additionally, we also utilized computational approaches for deep insight into the binding of these drugs with Hb and the results are well matched with our experimental results. Copyright © 2018 Elsevier B.V. All rights reserved.

49 CFR 659.23 - System security plan: contents.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 false System security plan: contents. 659.23 Section 659.23 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAIL FIXED GUIDEWAY SYSTEMS; STATE SAFETY OVERSIGHT Role of the State Oversight Agency § 659.23 System security...

17 CFR 230.405 - Definitions of terms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... purchased for the account of plan participants, at prices not in excess of current market prices at the time... specified in the plan and based upon average or current market prices at the time of purchase. Electronic... maintain a market for the registrant's securities. Equity security. The term equity security means any...

17 CFR 230.405 - Definitions of terms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... purchased for the account of plan participants, at prices not in excess of current market prices at the time... specified in the plan and based upon average or current market prices at the time of purchase. Electronic... maintain a market for the registrant's securities. Equity security. The term equity security means any...

17 CFR 230.405 - Definitions of terms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... purchased for the account of plan participants, at prices not in excess of current market prices at the time... specified in the plan and based upon average or current market prices at the time of purchase. Electronic... maintain a market for the registrant's securities. Equity security. The term equity security means any...

78 FR 43230 - Agency Information Collection Activities: Submission to OMB for Reinstatement, Without Change, of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-19

... Insured Credit Unions to maintain an information security program and an incident response plan that... Federally Insured Credit Unions to maintain an information security program and an incident response plan... credit unions to develop a written security program to safeguard sensitive member information. This...

78 FR 66788 - Joint Industry Plan; Order Approving Amendment No. 30 to the Joint Self-Regulatory Organization...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-06

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70793; File No. S7-24-89] Joint Industry Plan..., Consolidation and Dissemination of Quotation and Transaction Information for Nasdaq-Listed Securities Traded on... Exchange, Inc., Financial Industry Regulatory Authority, Inc., International Securities Exchange LLC...

National Aeronautics and Space Administration's (NASA) Automated Information Security Handbook

NASA Technical Reports Server (NTRS)

Roback, E.

1991-01-01

The NASA Automated Information Security Handbook provides NASA's overall approach to automated information systems security including discussions of such aspects as: program goals and objectives, assignment of responsibilities, risk assessment, foreign national access, contingency planning and disaster recovery, awareness training, procurement, certification, planning, and special considerations for microcomputers.

77 FR 45354 - Notification of Single Source Cooperative Agreement Award for Project Hope

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-31

... Support of National Health Security Strategy (2009) and Implementation Plan (2012) and Homeland Security... Directive-21 (2007) and the National Health Security Strategy (2009) and Implementation Plan (2012). In the... of a Health Affairs thematic issue that will identify, explore and propose policy options for...

75 FR 43528 - Seeking Public Comment on Draft National Health Security Strategy Biennial Implementation Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Seeking Public Comment on Draft National Health Security Strategy Biennial Implementation Plan AGENCY: Department of Health and Human... Interim Implementation Guide for the National Health Security Strategy of the United States of America...

The Relationship of Social Security Benefits and the Military Survivors Benefit Plan.

DTIC Science & Technology

1980-07-09

profound effect on the social security offset from the military survivors benefit plan (SBP). This study demonstrates the new social security computation...AD-ABO 088 AIR FORCE INST OF TECH WRIGHT-PATTERSON AFB ON SCHOOL-ETC F/B 513 THE RELATIONSHIP OF SOCIAL SECURITY BENEFITS AND THE MILITARY S-ETC(U...JUL 80 W C LETZKUS. C R MARGENTHALER UNCLASSIFIED AFIT-LS-80-3 I fllflfflffl..fl fl ’IilllllNO] LEVE1L 0 9THE RELATIONSHIP OF SOCIAL SECURITY BENEFITS

Processing and Fusion of Electro-Optic Information

DTIC Science & Technology

2001-04-01

UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP010886 TITLE: Processing and Fusion of Electro - Optic Information...component part numbers comprise the compilation report: ADP010865 thru ADP010894 UNCLASSIFIED 21-1 Processing and Fusion of Electro - Optic Information I...additional electro - optic (EO) sensor model within OOPSDG. It describes TM IT TT T T T performance estimates found prior to producing the New Ne- New

Characterization of an Opioid-Like Hibernation Induction Trigger

DTIC Science & Technology

1989-07-01

to HIT administration with a dose -reryonse relationship between the amount of adenosina dijphosphate (ADP) added and the extent of aggregation. However...despite the use of high doses of ADP. Our preliminary results suggest that one mechanism of prolonged organ survival following HIT administration may...HIT administration despite high dose ADP to stimulate aggregation . . . . 36 -3- INTRODUCTION A hibernation induction trigger (HIT) molecule derived

Staying Secure for School Safety

ERIC Educational Resources Information Center

Youngkin, Minu

2012-01-01

Proper planning and preventive maintenance can increase school security and return on investment. Preventive maintenance begins with planning. Through careful planning, education institutions can determine what is working and if any equipment, hardware or software needs to be replaced or upgraded. When reviewing a school's safety and security…

Evaluation of Amyloid Protective Factors and Alzheimer Disease Neurodegeneration Protective Factors in Elderly Individuals.

PubMed

Vemuri, Prashanthi; Knopman, David S; Lesnick, Timothy G; Przybelski, Scott A; Mielke, Michelle M; Graff-Radford, Jonathan; Murray, Melissa E; Roberts, Rosebud O; Vassilaki, Maria; Lowe, Val J; Machulda, Mary M; Jones, David T; Petersen, Ronald C; Jack, Clifford R

2017-06-01

While amyloid and neurodegeneration are viewed together as Alzheimer disease pathophysiology (ADP), the factors that influence amyloid and AD-pattern neurodegeneration may be considerably different. Protection from these ADP factors may be important for aging without significant ADP. To identify the combined and independent protective factors for amyloid and AD-pattern neurodegeneration in a population-based sample and to test the hypothesis that "exceptional agers" with advanced ages do not have significant ADP because they have protective factors for amyloid and neurodegeneration. This cohort study conducted a prospective analysis of 942 elderly individuals (70-≥90 years) with magnetic resonance imaging and Pittsburgh compound B-positron emission tomography scans enrolled in the Mayo Clinic Study of Aging, a longitudinal population-based study of cognitive aging in Olmsted County, Minnesota. We operationalized "exceptional aging" without ADP by considering individuals 85 years or older to be without significant evidence of ADP. We evaluated predictors including demographics, APOE, intellectual enrichment, midlife risk factors (physical inactivity, obesity, smoking, diabetes, hypertension, and dyslipidemia), and the total number of late-life cardiac and metabolic conditions. We used multivariate linear regression models to identify the combined and independent protective factors for amyloid and AD-pattern neurodegeneration. Using a subsample of the cohort 85 years of age or older, we computed Cohen d-based effect size estimations to compare the quantitative strength of each predictor variable in their contribution with exceptional aging without ADP. The study participants included 423 (45%) women and the average age of participants was 79.7 (5.9) years. Apart from demographics and the APOE genotype, only midlife dyslipidemia was associated with amyloid deposition. Obesity, smoking, diabetes, hypertension, and cardiac and metabolic conditions, but not intellectual enrichment, were associated with greater AD-pattern neurodegeneration. In the 85 years or older cohort, the Cohen d results showed small to moderate effects (effect sizes > 0.2) of several variables except job score and midlife hypertension in predicting exceptional aging without ADP. The protective factors that influence amyloid and AD-pattern neurodegeneration are different. "Exceptional aging" without ADP may be possible with a greater number of protective factors across the lifespan but warrants further investigation.

Comparison of percent body fat estimates using air displacement plethysmography and hydrodensitometry in adults and children.

PubMed

Demerath, E W; Guo, S S; Chumlea, W C; Towne, B; Roche, A F; Siervogel, R M

2002-03-01

The purpose of the study was to compare estimates of body density and percentage body fat from air displacement plethysmography (ADP) to those from hydrodensitometry (HD) in adults and children and to provide a review of similar recent studies. Body density and percentage body fat (% BF) were assessed by ADP and HD on the same day in 87 adults aged 18-69 y (41 males and 46 females) and 39 children aged 8-17 y (19 males and 20 females). Differences between measured and predicted thoracic gas volumes determined during the ADP procedure and the resultant effects of those differences on body composition estimates were also compared. In a subset of 50 individuals (31 adults and 19 children), reliability of ADP was measured and the relative ease or difficulty of ADP and HD were probed with a questionnaire. The coefficient of reliability between %BF on day 1 and day 2 was 96.4 in adults and 90.1 in children, and the technical error of measurement of 1.6% in adults and 1.8% in children. Using a predicted rather than a measured thoracic gas volume did not significantly affect percentage body fat estimates in adults, but resulted in overestimates of percentage body fat in children. Mean percentage body fat from ADP was higher than percentage body fat from HD, although this was statistically significant only in adults (29.3 vs 27.7%, P<0.05). The 95% confidence interval of the between-method differences for all subjects was -7 to +9% body fat, and the root mean square error (r.m.s.e.) was approximately 4% body fat. In the subset of individuals who were asked to compare the two methods, 46 out of 50 (92%) indicated that they preferred the ADP to HD. ADP is a reliable method of measuring body composition that subjects found preferable to underwater weighing. However, as shown here and in most other studies, there are differences in percentage body fat estimates assessed by the two methods, perhaps related to body size, age or other factors, that are sufficient to preclude ADP from being used interchangeably with underwater weighing on an individual basis.

Comparing replacement rates under private and federal retirement systems.

PubMed

Martin, Patricia P

One measure of the adequacy of retirement income is replacement rate - the percentage of pre-retirement salary that is available to a worker in retirement. This article compares salary replacement rates for private-sector employees of medium and large private establishments with those for federal employees under the Civil Service Retirement System and the Federal Employees Retirement System. Because there is no standard benefit formula to represent the variety of formulas available in the private sector, a composite defined benefit formula was developed using the characteristics of plans summarized in the Bureau of Labor Statistics Medium and Large Employer Plan Survey. The resulting "typical" private-sector defined benefit plan, with an accompanying defined contribution plan, was then compared with the two federal systems. The Civil Service Retirement System (CSRS) is a stand-alone defined benefit plan whose participants are not covered by Social Security. Until passage of the 1983 Amendments to Social Security Act, it was the only retirement plan for most federal civilian employees. Provisions of the 1983 Amendments were designed to restore long-term financial stability to the Social Security trust funds. One provision created the Federal Employees Retirement System (FERS), which covers federal employees hired after 1983. It was one of the provisions designed to restore long-term financial stability to the Social Security trust funds. FERS employees contribute to and are covered by Social Security. FERS, which is a defined benefit plan, also includes a basic benefit and a 401(k)-type plan known as the Thrift Savings Plan (TSP). To compare how retirees would fare under the three different retirement systems, benefits of employees retiring at age 65 with 35 years of service were calculated using hypothetical workers with steady earnings. Workers were classified according to a percentage of the average wage in the economy: low earners (45 percent), average earners (100 percent) high earners (160 percent), and maximum earners (earnings at the taxable maximum amount). Overall, this analysis found that: Excluding Social Security benefits and TSP and defined contribution annuities, CSRS retirees have a higher pre-retirement salary replacement rate than either FERS or private-sector retirees. Private-sector retirees, however, have higher replacement rate than their FERS counterparts. Including Social Security benefits but not TSP and defined contribution plan annuities, CSRS retirees who are maximum earners have a higher pre-retirement salary replacement rate (despite receiving no Social Security benefits) than FERS retirees with the same earnings. Private-sector retirees in all earnings categories have a higher replacement rate than federal retirees with the same earnings. Including Social Security and TSP and defined contribution plan annuities, private-sector retirees in all earnings categories have a higher replacement rate than federal retirees, but their rate is close to that of FERS retirees. The rate is higher for FERS retirees than for CSRS retirees in all earnings categories. This analysis shows that replacement creates could exceed 100 percent for FERS employees who contribute who contribute 6 percent of earnings to the TSP over full working career. Private-sector replacement rates were quite similar for those with both a defined benefit and a defined contribution pension plan. Social Security replacement rates make up the highest proportion of benefits for th private sector's lowest income quartile group. The replacement rate for 401(k) plans and the TSP account for a higher proportion of benefits than does Social Security for all other income groups, assuming the absence of a defined benefit plan.

Mobile Launch Platform Vehicle Assembly Area (SWMU 056) Biosparge Expansion Interim Measures Work Plan

NASA Technical Reports Server (NTRS)

Burcham, Michael S.; Daprato, Rebecca C.

2016-01-01

This document presents the design details for an Interim Measure (IM) Work Plan (IMWP) for the Mobile Launch Platform/Vehicle Assembly Building (MLPV) Area, located at the John F. Kennedy Space Center (KSC), Florida. The MLPV Area has been designated Solid Waste Management Unit Number 056 (SWMU 056) under KSC's Resource Conservation and Recovery Act (RCRA) Corrective Action Program. This report was prepared by Geosyntec Consultants (Geosyntec) for the National Aeronautics and Space Administration (NASA) under contract number NNK09CA02B and NNK12CA13B, project control number ENV1642. The Advanced Data Package (ADP) presentation covering the elements of this IMWP report received KSC Remediation Team (KSCRT) approval at the December 2015 Team Meeting; the meeting minutes are included in Appendix A.

Optimizing Security of Cloud Computing within the DoD

DTIC Science & Technology

2010-12-01

information security governance and risk management; application security; cryptography; security architecture and design; operations security; business ...governance and risk management; application security; cryptography; security architecture and design; operations security; business continuity...20 7. Operational Security (OPSEC).........................................................20 8. Business Continuity Planning (BCP) and Disaster

Computer Security: Governmentwide Planning Process Had Limited Impact. Report to the Chairman, Committee on Science, Space, and Technology, House of Representatives.

ERIC Educational Resources Information Center

General Accounting Office, Washington, DC. Information Management and Technology Div.

As required by the Computer Security Act of 1987, federal agencies have to identify systems that contain sensitive information and develop plans to safeguard them. The planning process was assessed in 10 civilian agencies as well as the extent to which they had implemented planning controls described in 22 selected plans. The National Institute of…

Cofilin-2 controls actin filament length in muscle sarcomeres

PubMed Central

Kremneva, Elena; Makkonen, Maarit H.; Skwarek-Maruszewska, Aneta; Gateva, Gergana; Michelot, Alphee; Dominguez, Roberto; Lappalainen, Pekka

2014-01-01

SUMMARY ADF/cofilins drive cytoskeletal dynamics by promoting the disassembly of ‘aged’ ADP-actin filaments. Mammals express several ADF/cofilin isoforms, but their specific biochemical activities and cellular functions have not been studied in detail. Here we demonstrate that the muscle-specific isoform cofilin-2 promotes actin filament disassembly in sarcomeres to control the precise length of thin filaments in the contractile apparatus. In contrast to other isoforms, cofilin-2 efficiently binds and disassembles both ADP- and ATP/ADP-Pi-actin filaments. We mapped surface-exposed cofilin-2-specific residues required for ATP-actin binding and propose that these residues function as an ‘actin nucleotide-state sensor’ among ADF/cofilins. The results suggest that cofilin-2 evolved specific biochemical and cellular properties allowing it to control actin dynamics in sarcomeres, where filament pointed ends may contain a mixture of ADP- and ATP/ADP-Pi-actin subunits. Our findings also offer a rationale for why cofilin-2 mutations in humans lead to myopathies. PMID:25373779

Mitochondrial respiratory control is lost during growth factor deprivation.

PubMed

Gottlieb, Eyal; Armour, Sean M; Thompson, Craig B

2002-10-01

The ability of cells to maintain a bioenergetically favorable ATP/ADP ratio confers a tight balance between cellular events that consume ATP and the rate of ATP production. However, after growth factor withdrawal, the cellular ATP/ADP ratio declines. To investigate these changes, mitochondria from growth factor-deprived cells isolated before the onset of apoptosis were characterized in vitro. Mitochondria from growth factor-deprived cells have lost their ability to undergo matrix condensation in response to ADP, which is accompanied by a failure to perform ADP-coupled respiration. At the time of analysis, mitochondria from growth factor-deprived cells were not depleted of cytochrome c and cytochrome c-dependent respiration was unaffected, demonstrating that the inhibition of the respiratory rate is not due to loss of cytochrome c. Agents that disrupt the mitochondrial outer membrane, such as digitonin, or maintain outer membrane exchange of adenine nucleotide, such as Bcl-x(L), restored ADP-dependent control of mitochondrial respiration. Together, these data suggest that the regulation of mitochondrial outer membrane permeability contributes to respiratory control.

Genetics of Psychosis in Alzheimer Disease.

PubMed

DeMichele-Sweet, Mary Ann A; Sweet, Robert A

2014-03-01

Psychosis occurs in approximately half of patients with Alzheimer disease (AD with psychosis, AD+P). AD+P patients have more rapid cognitive decline, greater behavioral symptoms, and higher mortality than do AD patients without psychosis. Studies in three independent cohorts have shown that psychosis in AD aggregates in families, with estimated heritability of 29.5 - 60.8%. These findings have motivated studies to investigate and uncover the genes responsible for the development of psychosis, with the ultimate goal of identifying potential biologic mechanisms that may serve as leads to specific therapies. Linkage analyses have implicated loci on chromosomes 2, 6, 7, 8, 15, and 21 with AD+P. Association studies of APOE do not support it as a risk gene for psychosis in AD. No other candidate genes, such as neurodegenerative and monoamine genes, show conclusive evidence of association with AD+P. However, a recent genome-side association study has produced some promising leads, including among them genes that have been associated with schizophrenia. This review summarizes the current knowledge of the genetic basis of AD+P.

31 CFR 10.6 - Enrollment as an enrolled agent or enrolled retirement plan agent.

Code of Federal Regulations, 2011 CFR

2011-07-01

... or enrolled retirement plan agent's name, prior address, new address, social security number or tax... individuals licensed to practice before the Internal Revenue Service who have a social security number or tax... Internal Revenue Service who have a social security number or tax identification number that ends with the...

Security Considerations for Archives: Rare Book, Manuscript, and Other Special Collections.

ERIC Educational Resources Information Center

Cupp, Christian M.

The first of six sections in this guide to security for special collections in archives and libraries discusses the importance of security and the difficulty of preventing theft of archival materials. The second section, which focuses on planning, recommends an inservice training program for staff, a planned communications network between library…

Planning for Effective Security at Campus Special Events.

ERIC Educational Resources Information Center

Bromley, Max L.

1984-01-01

Factors to consider in assuring security for student events on campus are discussed, based on the experience of the University of South Florida, which has developed, tested, and critiqued a system of planning security. Even though special events vary significantly in type and purpose, some questions should be answered in advance, with the…

32 CFR 199.8 - Double coverage.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., except in the case of a plan administered under title XIX of the Social Security Act (42 U.S.C. 1396 et... not include: (i) Plans administered under title XIX of the Social Security Act (Medicaid); (ii... under Title XIX of the Social Security Act (Medicaid) are never considered to be available in the...

76 FR 20377 - Applications and Amendments to Facility Operating Licenses Involving Proposed No Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-12

... amendment requests approval of the Exelon Cyber Security Plan, provides an Implementation Schedule, and adds... require Exelon to fully implement and maintain in effect all provisions of the approved Cyber Security..., Revision 6, ``Cyber Security Plan for Nuclear Power Reactors.'' Basis for proposed no significant hazards...

75 FR 62592 - Applications and Amendments to Facility Operating Licenses Involving Proposed No Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-12

... Operating Licenses include: (1) The proposed Cyber Security Plan for CCNPP, Ginna, and NMPNS, (2) an... provisions of the Nuclear Regulatory Commission-approved Cyber Security Plan for CCNPP, Ginna, and NMPNS as... Communication Systems and Networks,'' establish the requirements for a cyber security program. This regulation...

75 FR 36125 - Office of New Reactors; Proposed Revision to Standard Review Plan, Section 13.6.2, Revision 1 on...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-24

... Standard Review Plan, Section 13.6.2, Revision 1 on Physical Security--Design Certification AGENCY: Nuclear... comment on NUREG-0800, ``Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants,'' on a proposed Revision 1 to Standard Review Plan (SRP), Section 13.6.2 on ``Physical Security...

78 FR 65733 - Joint Industry Plan; Notice of Filing and Immediate Effectiveness of Amendment to the Plan for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70764; File No. 4-443] Joint Industry Plan; Notice of Filing and Immediate Effectiveness of Amendment to the Plan for the Purpose of Developing and Implementing Procedures Designed To Facilitate the Listing and Trading of Standardized Options To Add Miami International Securities Exchange, LLC (...

78 FR 73202 - Review and Revision of the National Critical Infrastructure Security and Resilience (NCISR...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-05

...This Request for Information (RFI) notice informs the public that the Department of Homeland Security's (DHS) Science and Technology Directorate (S&T) is currently developing a National Critical Infrastructure Security and Resilience Research and Development Plan (NCISR R&D Plan) to conform to the requirements of Presidential Policy Directive 21, Critical Infrastructure Security and Resilience. As part of a comprehensive national review process, DHS solicits public comment on issues or language in the NCISR R&D Plan that need to be included. Critical infrastructure includes both cyber and physical components, systems, and networks for the sixteen established ``critical infrastructures''.

PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

PubMed Central

Gupte, Rebecca; Liu, Ziying; Kraus, W. Lee

2017-01-01

The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates. Supporting these advances is a host of methodological approaches from chemical biology, proteomics, genomics, cell biology, and genetics that have propelled new discoveries in the field. New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer. These studies have begun to reveal the promising ways in which PARPs may be targeted therapeutically for the treatment of disease. In this review, we discuss these topics and relate them to the future directions of the field. PMID:28202539

ADP1 Affects Plant Architecture by Regulating Local Auxin Biosynthesis

PubMed Central

Li, Shibai; Qin, Genji; Novák, Ondřej; Pěnčík, Aleš; Ljung, Karin; Aoyama, Takashi; Liu, Jingjing; Murphy, Angus; Gu, Hongya; Tsuge, Tomohiko; Qu, Li-Jia

2014-01-01

Plant architecture is one of the key factors that affect plant survival and productivity. Plant body structure is established through the iterative initiation and outgrowth of lateral organs, which are derived from the shoot apical meristem and root apical meristem, after embryogenesis. Here we report that ADP1, a putative MATE (multidrug and toxic compound extrusion) transporter, plays an essential role in regulating lateral organ outgrowth, and thus in maintaining normal architecture of Arabidopsis. Elevated expression levels of ADP1 resulted in accelerated plant growth rate, and increased the numbers of axillary branches and flowers. Our molecular and genetic evidence demonstrated that the phenotypes of plants over-expressing ADP1 were caused by reduction of local auxin levels in the meristematic regions. We further discovered that this reduction was probably due to decreased levels of auxin biosynthesis in the local meristematic regions based on the measured reduction in IAA levels and the gene expression data. Simultaneous inactivation of ADP1 and its three closest homologs led to growth retardation, relative reduction of lateral organ number and slightly elevated auxin level. Our results indicated that ADP1-mediated regulation of the local auxin level in meristematic regions is an essential determinant for plant architecture maintenance by restraining the outgrowth of lateral organs. PMID:24391508

Single-molecule Analysis of Inhibitory Pausing States of V1-ATPase*

PubMed Central

Uner, Naciye Esma; Nishikawa, Yoshihiro; Okuno, Daichi; Nakano, Masahiro; Yokoyama, Ken; Noji, Hiroyuki

2012-01-01

V1-ATPase, the hydrophilic V-ATPase domain, is a rotary motor fueled by ATP hydrolysis. Here, we found that Thermus thermophilus V1-ATPase shows two types of inhibitory pauses interrupting continuous rotation: a short pause (SP, 4.2 s) that occurred frequently during rotation, and a long inhibitory pause (LP, >30 min) that terminated all active rotations. Both pauses occurred at the same angle for ATP binding and hydrolysis. Kinetic analysis revealed that the time constants of inactivation into and activation from the SP were too short to represent biochemically predicted ADP inhibition, suggesting that SP is a newly identified inhibitory state of V1-ATPase. The time constant of inactivation into LP was 17 min, consistent with one of the two time constants governing the inactivation process observed in bulk ATPase assay. When forcibly rotated in the forward direction, V1 in LP resumed active rotation. Solution ADP suppressed the probability of mechanical activation, suggesting that mechanical rotation enhanced inhibitory ADP release. These features were highly consistent with mechanical activation of ADP-inhibited F1, suggesting that LP represents the ADP-inhibited state of V1-ATPase. Mechanical activation largely depended on the direction and angular displacement of forced rotation, implying that V1-ATPase rotation modulates the off rate of ADP. PMID:22736762

Identification and characterization of a novel P2Y 12 variant in a patient diagnosed with type 1 von Willebrand disease in the European MCMDM-1VWD study.

PubMed

Daly, Martina E; Dawood, Ban B; Lester, William A; Peake, Ian R; Rodeghiero, Francesco; Goodeve, Anne C; Makris, Michael; Wilde, Jonathan T; Mumford, Andrew D; Watson, Stephen P; Mundell, Stuart J

2009-04-23

We investigated whether defects in the P2Y(12) ADP receptor gene (P2RY12) contribute to the bleeding tendency in 92 index cases enrolled in the European MCMDM-1VWD study. A heterozygous mutation, predicting a lysine to glutamate (K174E) substitution in P2Y(12), was identified in one case with mild type 1 von Willebrand disease (VWD) and a VWF defect. Platelets from the index case and relatives carrying the K174E defect changed shape in response to ADP, but showed reduced and reversible aggregation in response to 10 muM ADP, unlike the maximal, sustained aggregation observed in controls. The reduced response was associated with an approximate 50% reduction in binding of [(3)H]2MeS-ADP to P2Y(12), whereas binding to the P2Y(1) receptor was normal. A hemagglutinin-tagged K174E P2Y(12) variant showed surface expression in CHO cells, markedly reduced binding to [(3)H]2MeS-ADP, and minimal ADP-mediated inhibition of forskolin-induced adenylyl cyclase activity. Our results provide further evidence for locus heterogeneity in type 1 VWD.

ADP1 affects plant architecture by regulating local auxin biosynthesis.

PubMed

Li, Ruixi; Li, Jieru; Li, Shibai; Qin, Genji; Novák, Ondřej; Pěnčík, Aleš; Ljung, Karin; Aoyama, Takashi; Liu, Jingjing; Murphy, Angus; Gu, Hongya; Tsuge, Tomohiko; Qu, Li-Jia

2014-01-01

Plant architecture is one of the key factors that affect plant survival and productivity. Plant body structure is established through the iterative initiation and outgrowth of lateral organs, which are derived from the shoot apical meristem and root apical meristem, after embryogenesis. Here we report that ADP1, a putative MATE (multidrug and toxic compound extrusion) transporter, plays an essential role in regulating lateral organ outgrowth, and thus in maintaining normal architecture of Arabidopsis. Elevated expression levels of ADP1 resulted in accelerated plant growth rate, and increased the numbers of axillary branches and flowers. Our molecular and genetic evidence demonstrated that the phenotypes of plants over-expressing ADP1 were caused by reduction of local auxin levels in the meristematic regions. We further discovered that this reduction was probably due to decreased levels of auxin biosynthesis in the local meristematic regions based on the measured reduction in IAA levels and the gene expression data. Simultaneous inactivation of ADP1 and its three closest homologs led to growth retardation, relative reduction of lateral organ number and slightly elevated auxin level. Our results indicated that ADP1-mediated regulation of the local auxin level in meristematic regions is an essential determinant for plant architecture maintenance by restraining the outgrowth of lateral organs.

An enzyme-linked immunosorbent assay-based system for determining the physiological level of poly(ADP-ribose) in cultured cells.

PubMed

Ida, Chieri; Yamashita, Sachiko; Tsukada, Masaki; Sato, Teruaki; Eguchi, Takayuki; Tanaka, Masakazu; Ogata, Shin; Fujii, Takahiro; Nishi, Yoshisuke; Ikegami, Susumu; Moss, Joel; Miwa, Masanao

2016-02-01

PolyADP-ribosylation is mediated by poly(ADP-ribose) (PAR) polymerases (PARPs) and may be involved in various cellular events, including chromosomal stability, DNA repair, transcription, cell death, and differentiation. The physiological level of PAR is difficult to determine in intact cells because of the rapid synthesis of PAR by PARPs and the breakdown of PAR by PAR-degrading enzymes, including poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribosylhydrolase 3. Artifactual synthesis and/or degradation of PAR likely occurs during lysis of cells in culture. We developed a sensitive enzyme-linked immunosorbent assay (ELISA) to measure the physiological levels of PAR in cultured cells. We immediately inactivated enzymes that catalyze the synthesis and degradation of PAR. We validated that trichloroacetic acid is suitable for inactivating PARPs, PARG, and other enzymes involved in metabolizing PAR in cultured cells during cell lysis. The PAR level in cells harvested with the standard radioimmunoprecipitation assay buffer was increased by 450-fold compared with trichloroacetic acid for lysis, presumably because of activation of PARPs by DNA damage that occurred during cell lysis. This ELISA can be used to analyze the biological functions of polyADP-ribosylation under various physiological conditions in cultured cells. Copyright © 2015 Elsevier Inc. All rights reserved.

External validation of the emergency department assessment of chest pain score accelerated diagnostic pathway (EDACS-ADP).

PubMed

Flaws, Dylan; Than, Martin; Scheuermeyer, Frank Xavier; Christenson, James; Boychuk, Barbara; Greenslade, Jaimi H; Aldous, Sally; Hammett, Christopher J; Parsonage, William A; Deely, Joanne M; Pickering, John W; Cullen, Louise

2016-09-01

The emergency department assessment of chest pain score accelerated diagnostic pathway (EDACS-ADP) facilitates low-risk ED chest pain patients early to outpatient investigation. We aimed to validate this rule in a North American population. We performed a retrospective validation of the EDACS-ADP using 763 chest pain patients who presented to St Paul's Hospital, Vancouver, Canada, between June 2000 and January 2003. Patients were classified as low risk if they had an EDACS <16, no new ischaemia on ECG and non-elevated serial 0-hour and 2-hour cardiac troponin concentrations. The primary outcome was the number of patients who had a predetermined major adverse cardiac event (MACE) at 30 days after presentation. Of the 763 patients, 317 (41.6%) were classified as low risk by the EDACS-ADP. The sensitivity, specificity, negative predictive value and positive predictive value of the EDACS-ADP for 30-day MACE were 100% (95% CI 94.2% to 100%), 46.4% (95% CI 42.6% to 50.2%), 100% (95% CI 98.5% to 100.0%) and 17.5% (95% CI 14.1% to 21.3%), respectively. This study validated the EDACS-ADP in a novel context and supports its safe use in a North American population. It confirms that EDACS-ADP can facilitate progression to early outpatient investigation in up to 40% of ED chest pain patients within 2 hours. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Poly(ADP-ribose) polymerase-independent potentiation of nitrosourea cytotoxicity by 3-aminobenzamide in human malignant glioma cells.

PubMed

Winter, S; Weller, M

2000-06-16

Poly(ADP-ribose) polymerase is a zinc-finger DNA-binding protein that detects specifically DNA strand breaks generated by genotoxic agents and is thought to be involved in DNA repair. Here, we examined the effects of 3-aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, on the chemosensitivity of human malignant glioma cells. 3-Aminobenzamide selectively potentiated the cytotoxicity of the nitrosoureas, nimustine, carmustine and lomustine in 10 of 12 human malignant glioma cell lines. In contrast, 3-aminobenzamide did not modulate the cytotoxic effects of doxorubicine, teniposide, vincristine, camptothecin or cytarabine. The nitrosoureas did not induce poly(ADP-ribose) polymerase activity in the glioma cells. Ectopic expression of truncated poly(ADP-ribose) polymerase containing the poly(ADP-ribose) polymerase DNA-binding domain, which acts as a dominant-negative mutant, in LN-18 or LN-229 cells did not alter the 3-aminobenzamide effect on nitrosourea-mediated cytotoxicity. Thus, 3-aminobenzamide may target another nicotinamide adenine dinucleotide (NAD)-requiring enzyme, but not poly(ADP-ribose) polymerase, when enhancing nitrosourea cytotoxicity in human malignant glioma cells. Carmustine cytotoxicity was associated with a G2/M arrest. Coexposure to carmustine and 3-aminobenzamide overcame this G2/M arrest in T98G cells, which are sensitized to carmustine by 3-aminobenzamide, but not in U251MG cells, which are refractory to 3-aminobenzamide-mediated sensitization to carmustine. Thus, 3-aminobenzamide-mediated sensitization to carmustine cytotoxicity may result from interference with the stable G2/M arrest response to carmustine in human glioma cells.

Comparison of Far-Field Noise for Three Significantly Different Model Turbofans

NASA Technical Reports Server (NTRS)

Woodward, Richard P.

2008-01-01

Far-field noise sound power level (PWL) spectra and overall sound pressure level (OASPL) directivities were compared for three significantly different model fan stages which were tested in the NASA Glenn 9x15 Low Speed Wind Tunnel. The test fans included the Advanced Ducted Propulsor (ADP) Fan1, the baseline Source Diagnostic Test (SDT) fan, and the Quiet High Speed Fan2 (QHSF2) These fans had design rotor tangential tip speeds from 840 to 1474 ft/s and stage pressure ratios from 1.29 to 1.82. Additional parameters included rotor-stator spacing, stator sweep, and downstream support struts. Acoustic comparison points were selected on the basis of stage thrust. Acoustic results for the low tip speed/low pressure ratio fan (ADP Fan1) were thrust-adjusted to show how a geometrically-scaled version of this fan might compare at the higher design thrust levels of the other two fans. Lowest noise levels were typically observed for ADP Fan1 (which had a radial stator) and for the intermediate tip speed fan (Source Diagnostics Test, SDT, R4 rotor) with a swept stator. Projected noise levels for the ADP fan to the SDT swept stator configuration at design point conditions showed the fans to have similar noise levels. However, it is possible that the ADP fan could be 2 to 3 dB quieter with incorporation of a swept stator. Benefits of a scaled ADP fan include avoidance of multiple pure tones associated with transonic and higher blade tip speeds. Penalties of a larger size ADP fan would include increased nacelle size and drag.

Comparison of Far-field Noise for Three Significantly Different Model Turbofans

NASA Technical Reports Server (NTRS)

Woodward, Richard P.

2008-01-01

Far-field noise sound power level (PWL) spectra and overall sound pressure level (OASPL) directivities were compared for three significantly different model fan stages which were tested in the NASA Glenn 9 15 Low Speed Wind Tunnel. The test fans included the Advanced Ducted Propulsor (ADP) Fan1, the baseline Source Diagnostic Test (SDT) fan, and the Quiet High Speed Fan2 (QHSF2). These fans had design rotor tangential tip speeds from 840 to 1474 ft/s and stage pressure ratios from 1.29 to 1.82. Additional parameters included rotor-stator spacing, stator sweep, and downstream support struts. Acoustic comparison points were selected on the basis of stage thrust. Acoustic results for the low tip speed/low pressure ratio fan (ADP Fan1) were thrust-adjusted to show how a geometrically-scaled version of this fan might compare at the higher design thrust levels of the other two fans. Lowest noise levels were typically observed for ADP Fan1 (which had a radial stator) and for the intermediate tip speed fan (Source Diagnostics Test, SDT, R4 rotor) with a swept stator. Projected noise levels for the ADP fan to the SDT swept stator configuration at design point conditions showed the fans to have similar noise levels. However, it is possible that the ADP fan could be 2 to 3 dB quieter with incorporation of a swept stator. Benefits of a scaled ADP fan include avoidance of multiple pure tones associated with transonic and higher blade tip speeds. Penalties of a larger size ADP fan would include increased nacelle size and drag.

Whole-Body Computed Tomography-Based Body Mass and Body Fat Quantification: A Comparison to Hydrostatic Weighing and Air Displacement Plethysmography.

PubMed

Gibby, Jacob T; Njeru, Dennis K; Cvetko, Steve T; Heiny, Eric L; Creer, Andrew R; Gibby, Wendell A

We correlate and evaluate the accuracy of accepted anthropometric methods of percent body fat (%BF) quantification, namely, hydrostatic weighing (HW) and air displacement plethysmography (ADP), to 2 automatic adipose tissue quantification methods using computed tomography (CT). Twenty volunteer subjects (14 men, 6 women) received head-to-toe CT scans. Hydrostatic weighing and ADP were obtained from 17 and 12 subjects, respectively. The CT data underwent conversion using 2 separate algorithms, namely, the Schneider method and the Beam method, to convert Hounsfield units to their respective tissue densities. The overall mass and %BF of both methods were compared with HW and ADP. When comparing ADP to CT data using the Schneider method and Beam method, correlations were r = 0.9806 and 0.9804, respectively. Paired t tests indicated there were no statistically significant biases. Additionally, observed average differences in %BF between ADP and the Schneider method and the Beam method were 0.38% and 0.77%, respectively. The %BF measured from ADP, the Schneider method, and the Beam method all had significantly higher mean differences when compared with HW (3.05%, 2.32%, and 1.94%, respectively). We have shown that total body mass correlates remarkably well with both the Schneider method and Beam method of mass quantification. Furthermore, %BF calculated with the Schneider method and Beam method CT algorithms correlates remarkably well with ADP. The application of these CT algorithms have utility in further research to accurately stratify risk factors with periorgan, visceral, and subcutaneous types of adipose tissue, and has the potential for significant clinical application.

The Effect of China’s Scramble for Resources and African Resource Nationalism on the Supply of Strategic Southern African Minerals: What Can the United States Do?

DTIC Science & Technology

2010-01-01

strategic partnerships, national security planning (and theater security cooperation) and US Africa Command (AFRICOM) in securing long term access to...A potential constraint on the supply of strategic minerals is the lack of a US industrial policy and contingency plans in case the flow of... planning for various contingencies, particularly for the 2020s and beyond. The region contains high concentrations of platinum group metals (PGMs

41 CFR 102-192.70 - What security policies and plans must we have?

Code of Federal Regulations, 2014 CFR

2014-01-01

... and plans must we have? 102-192.70 Section 102-192.70 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION ADMINISTRATIVE PROGRAMS... plans must we have? (a) You must have a written mail security policy that applies throughout the agency...

41 CFR 102-192.70 - What security policies and plans must we have?

Code of Federal Regulations, 2010 CFR

2010-07-01

... and plans must we have? 102-192.70 Section 102-192.70 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION ADMINISTRATIVE PROGRAMS... plans must we have? (a) You must have a written mail security policy that applies throughout the agency...

41 CFR 102-192.70 - What security policies and plans must we have?

Code of Federal Regulations, 2011 CFR

2011-01-01

... and plans must we have? 102-192.70 Section 102-192.70 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION ADMINISTRATIVE PROGRAMS... plans must we have? (a) You must have a written mail security policy that applies throughout the agency...

41 CFR 102-192.70 - What security policies and plans must we have?

Code of Federal Regulations, 2012 CFR

2012-01-01

... and plans must we have? 102-192.70 Section 102-192.70 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION ADMINISTRATIVE PROGRAMS... plans must we have? (a) You must have a written mail security policy that applies throughout the agency...

75 FR 27927 - Diversification Requirements for Certain Defined Contribution Plans

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-19

... section 414(l) with respect to any other defined benefit plan or defined contribution plan maintained by... disclosure of the fund's portfolio holdings (for example, Form N-CSR, ``Certified Shareholder Report of... securities, as well as a direct or indirect benefit that is conditioned on investment in employer securities...

Dynamics of platelet glycoprotein IIb-IIIa receptor expression and fibrinogen binding. I. Quantal activation of platelet subpopulations varies with adenosine diphosphate concentration.

PubMed Central

Frojmovic, M. M.; Mooney, R. F.; Wong, T.

1994-01-01

We have previously reported that maximal platelet activation with adenosine diphosphate (100 microM ADP) causes rapid expression of all GPIIb-IIIa receptors for fibrinogen (FgR) (< 1-3 s), measured with FITC-labeled PAC1 by flow cytometry. We have extended these studies to examine the effects of ADP concentration on the graded expression and Fg occupancy of GPIIb-IIIa receptors. Human citrated platelet-rich plasma, diluted 10-fold with Walsh-albumin-Mg+2 (2 mM), was treated with ADP (0.1-100 microM). The rates of GPIIb-IIIa receptor expression or Fg binding were measured in unstirred samples by flow cytometry, using FITC-labeled monoclonal antibodies (mAb) PAC1 and 9F9, respectively, from on-rates, using increasing times between mAb and ADP additions. Fibrinogen receptors were all expressed rapidly at low (1 microM) or high (100 microM) ADP (few seconds), whereas Fg occupancy was 50% of maximal by about 2 min. The maximal extent of GPIIb-IIIa receptor expression and Fg occupancy was determined from maximal binding (Flmax) at 30 min incubation with PAC1 or 9F9. On-rates and maximal extents of binding for either PAC1 or 9F9 probes showed identical [ADP]-response profiles ("KD" approximately 1.4 +/- 0.1 microM). However, Flmax studies showed bimodal histograms consisting of "resting" (Po) and maximally "activated" (P*) platelets for both PAC1 and 9F9 binding, with the fraction of "activated" platelets increasing with ADP concentration. The data best fit a model where platelet subpopulations are "quantally" transformed from Po to P*, expressing all GPIIb-IIIa receptors, rapidly filled by Fg, but "triggered" at critical ADP concentrations. Larger, but not the largest, platelets appear to be the most sensitive subpopulation. The implications for clinical studies are discussed, and the relationship to dynamics of aggregation are described in a companion paper. PMID:7858143

High-resolution velocimetry in energetic tidal currents using a convergent-beam acoustic Doppler profiler

NASA Astrophysics Data System (ADS)

Sellar, Brian; Harding, Samuel; Richmond, Marshall

2015-08-01

An array of single-beam acoustic Doppler profilers has been developed for the high resolution measurement of three-dimensional tidal flow velocities and subsequently tested in an energetic tidal site. This configuration has been developed to increase spatial resolution of velocity measurements in comparison to conventional acoustic Doppler profilers (ADPs) which characteristically use divergent acoustic beams emanating from a single instrument. This is achieved using geometrically convergent acoustic beams creating a sample volume at the focal point of 0.03 m3. Away from the focal point, the array is also able to simultaneously reconstruct three-dimensional velocity components in a profile throughout the water column, and is referred to herein as a convergent-beam acoustic Doppler profiler (C-ADP). Mid-depth profiling is achieved through integration of the sensor platform with the operational commercial-scale Alstom 1 MW DeepGen-IV Tidal Turbine deployed at the European Marine Energy Center, Orkney Isles, UK. This proof-of-concept paper outlines the C-ADP system configuration and comparison to measurements provided by co-installed reference instrumentation. Comparison of C-ADP to standard divergent ADP (D-ADP) velocity measurements reveals a mean difference of 8 mm s-1, standard deviation of 18 mm s-1, and an order of magnitude reduction in realisable length scale. C-ADP focal point measurements compared to a proximal single-beam reference show peak cross-correlation coefficient of 0.96 over 4.0 s averaging period and a 47% reduction in Doppler noise. The dual functionality of the C-ADP as a profiling instrument with a high resolution focal point make this configuration a unique and valuable advancement in underwater velocimetry enabling improved quantification of flow turbulence. Since waves are simultaneously measured via profiled velocities, pressure measurements and surface detection, it is expected that derivatives of this system will be a powerful tool in wave-current interaction studies.

Safe teleradiology: information assurance as project planning methodology.

PubMed

Collmann, Jeff; Alaoui, Adil; Nguyen, Dan; Lindisch, David

2005-01-01

The Georgetown University Medical Center Department of Radiology used a tailored version of OCTAVE, a self-directed information security risk assessment method, to design a teleradiology system that complied with the regulation implementing the security provisions of the Health Insurance Portability and Accountability Act (HIPAA) of 1996. The system addressed threats to and vulnerabilities in the privacy and security of protected health information. By using OCTAVE, Georgetown identified the teleradiology program's critical assets, described threats to the assurance of those assets, developed and ran vulnerability scans of a system pilot, evaluated the consequences of security breaches, and developed a risk management plan to mitigate threats to program assets, thereby implementing good information assurance practices. This case study illustrates the basic point that prospective, comprehensive planning to protect the privacy and security of an information system strategically benefits program management as well as system security.

Evaluation of Aggregometery Parameters and Efficacy of Plavix versus Clopidex in Patients Suffering from Ischemic Heart Disease: A Randomized Double Blind Clinical Trial.

PubMed

Shohrati, Majid; Moshkani, Maryam; Pishgoo, Bahram; Ahmadinejad, Minoo; Najafian, Nastaran; Najafian, Bita; Kazemisaleh, Davoud

2014-02-01

Ischemic heart disease is the leading cause of death in most societies. In a pathophysiologic point of view, it chiefly results from the formation of thrombus in coronary arteries which could not be only prevented by aspirin. Many of clinical trials have shown the long-term benefits of antiplatelet drugs in reducing the risk of thrombotic accidents. Clopidogrel is a thienopyridine derivative used to prevent platelets from adhering together by direct inhibition of Adenosine diphosphate (ADP), the major factor behind platelets aggregation. Sanofi-Aventis and Bristol-Myers are companies that produce Clopidogrel by the name of Clopidogrel bisulfate. Its trade name is Plavix, nonetheless in Iran it is distributed under the name of Clopidex by Exir Company. In this study we are to compare Plavix and Clopidex in terms of efficacy as well as aggregometry parameters like ADP and PRP (Platelet Rich Plasma). This is a double blind clinical trial in which we had two groups of patients suffering from Ischemic heart disease who were selected by inclusion criteria. Group A (36 patients) took Plavix (75 mg/d) and group B (36 patients) used clopidex (75 mg/d) both for 30 days. The aggregometry parameters also consisted of PRP and ADP that were run on the patients before and after the study. Finally, a comparison of aforementioned tests, quality of life, lab parameters and compliance in both groups was provided. In groups A and B, the mean levels of PRP before the study were 348000 and 340000/µL respectively. The ADPs were also 73/76 and 68/07 µM that showed no significant difference (P > 0.05).The Means of ADP5 in group A before and after the study were 66.40 and 43.84 µM respectively that there was significant difference (P = 0.001). The Means of ADP5 in group B before and after the study were 58.04 and 40.16 µM respectively that there was significant difference (P < 0.001).The Means of ADP20 in group A before and after the study were 73.76 and 54.97 µM respectively which showed significant difference (P < 0.001). The Means of ADP20 in group B before and after the study were 68.07 and 52.49 µM respectively which showed significant difference (P = 0.001). Difference of ADP5 between group A and B was not significant (P = 0.495). Difference of ADP20 between group A and B was not significant (P = 0.721). The Means of PRP in group A before and after the study were 348000 and 335000/ µL respectively that there was no significant difference (P = 0.66). The Means of PRP in group B before and after the study were 340000 and 336000/ µL respectively that indicated no significant difference (P = 0.81). Difference of PRP between group A and B was not significant (P = 0.563). Our findings suggested that both drugs significantly lessen the ADP level; even so there was no significant difference between two groups in PRP and ADP factors.

Availability/Operational Readiness Test Subsystem Cost Trade-Offs.

DTIC Science & Technology

1980-05-01

LNFAIL Digital AACS 31 914 203 153 34 2060 3320 2166 18980 9.9 ADP/COMPU 48 2048 612 424 71 9332 6540 5594 99572 11.5 ADP/DRUM 47 1995 260 517 10 1195...1650 466 12750 9.5 ADP/SAC 43 2495 798 332 31 4335 3150 1992 45400 10.7 A0P/SDC 41 2048 684 442 46 3595 5000 2302 38358 10.6 ADP/SGSA 45 2494 810 412...DIM/FL 2 75 460 23 3 77 250 44 780 6.7 FDIS/HSI 8 285 39 86 8 71 400 186 900 6.8 FDIS/ VDI 7 144 25 74 6 29 270 185 500 6.2 GCU 6 242 83 145 6 58 320

Novel bacterial ADP-ribosylating toxins: structure and function

PubMed Central

Simon, Nathan C.; Aktories, Klaus; Barbieri, Joseph T.

2018-01-01

Preface Bacterial ADP-ribosyltransferase toxins (bARTTs) transfer ADP-ribose to eukaryotic proteins to promote bacterial pathogenesis. In this review we use prototype bARTTs, such as diphtheria and pertussis toxins, as references for the characterization of several new bARTTs from human, insect, and plant pathogens, which were identified recently through bioinformatic analyses. Several of these toxins, including Cholix toxin from Vibrio cholerae, SpyA from Streptococcus pyogenes, HopU1 from Pseudomonas syringae, and the Tcc toxins from Photorhabdus luminescens, ADP-ribosylate novel substrates and possess unique organizations, which distinguish them from the reference toxins. The characterization of these toxins extends our appreciation for the variety of structure-function properties possessed by bARTTs and their roles in bacterial pathogenesis. PMID:25023120

75 FR 36126 - Office of New Reactors; Proposed Revision to Standard Review Plan Section 13.6.3, Revision 1 on...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-24

... Standard Review Plan Section 13.6.3, Revision 1 on Physical Security--Early Site Permit AGENCY: Nuclear... comment on NUREG-0800, ``Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants,'' on a proposed Revision 1 to Standard Review Plan (SRP), Section 13.6.3 on ``Physical Security...

75 FR 69709 - Office of New Reactors; Notice of Availability of the Final Staff Guidance; Standard Review Plan...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-15

... the Final Staff Guidance; Standard Review Plan, Section 13.6.6, Revision 0 on Cyber Security Plan... Reports for Nuclear Power Plants,'' Section 13.6.6, Revision 0 on ``Cyber Security Plan'' (Agencywide.... Disposition: On May 13, 2010, the NRC staff issued the proposed Revision 0 on SRP Section 13.6.6 on ``Cyber...

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

Troy Hiltbrand; Daniel Jones

As we look at the cyber security ecosystem, are we planning to fight the battle as we did yesterday, with firewalls and intrusion detection systems (IDS), or are we sensing a change in how security is evolving and planning accordingly? With the technology enablement and possible financial benefits of cloud computing, the traditional tools for establishing and maintaining our cyber security ecosystems are being dramatically altered.

Strategic planning for national security: Lessons from business experience. Interim report

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

Bracken, P.

1990-02-01

United States defense planning is at a crossroads and it is therefore useful to review not only discrete issues, but even basic concepts of strategic planning. This Note reviews concepts used in the business world to build insights about how to view current and prospective problems, opportunities, and choices. The author draws upon the business literature for both ideas and metaphors. He observes that U.S. national security planning could profit greatly from an approach that distinguishes among core, environmental, and hedging strategies, and that considers security analogs to such business concepts as defining the business, dealing with new competitors, controllingmore » the intensity of competition, entry and exit barriers, and the need to redeploy assets and restructure the organization. He then relates these concepts to specific problems of national security interest.« less

Generating capacity in US electric utilities: How is it used? How much is needed over the decade

NASA Astrophysics Data System (ADS)

Keelin, T. W.; Oatman, E. N.; Gent, M. R.

1982-10-01

This report addresses: how US generating capacity is used to supply today's consumers with electricity; whether new capacity planned over the next decade is enough to provide a secure supply of electricity; how delays and cancellations of planned capacity would result in higher electricity costs and threaten the security of electricity supply; and how today's decisions determine electricity supply for the next decade and beyond. It is concluded that there is not an electricity supply crisis currently, but there is a planning crisis. This conclusion is based on the following: existing capacity supplies current needs, but provides little room for economic growth; new capacity is planned to provide a secure supply of electricity for the demand projected by utilities; if demand is lower, planned capacity will reduce costs and, if demand is higher, planned capacity will not be adequate; planned capacity may not be realized.

Adenine nucleotide transport in sonic submitochondrial particles. Kinetic properties and binding of specific inhibitors.

PubMed

Lauquin, G J; Villiers, C; Michejda, J W; Hryniewiecka, L V; Vignais, P V

1977-05-11

1. A procedure for preparation of sonic submitochondrial particles competent for adenine nucleotide transport is described. ADP or ATP transport was assayed, in the presence of oligomycin, in a saline medium made of 0.125 M KCl, 1 mM EDTA, 10 mM 4-morpholinopropane sulfonic acid buffer, pH 6.5. 2. Sonic particles transport ADP and ATP by an exchange diffusion process. Externally added ADP (or ATP) is exchanged with internal ADP and ATP with a stoichiometry of one to one. The V value for ADP transport 5 degrees C was between 2 and 3 nmol/min per mg protein. 3. The transport system in sonic particles is specific for ADP and ATP. It is strongly dependent on temperature. The activation energy between 0 and 9 degrees C is approx. 35 kcal/mol. The optimum pH is 6.5, 4, Like in intact mitochondria, externally added ADP is transported into sonic particles faster at a given concentration than externally added ATP. The V value for ADP transport is 1.5-2 times higher than the V value for ATP transport. 5. The transition from the energized to the deenergized state in sonic particles results in a decrease of the pH gradient across the membrane (internal pH less than external pH) and in a 2-4 fold increase in the Km value for ATP. This latter effect is opposite that found for transport of added ATP in intact mitochondria (Souverijn, J.H.M., Huisman, L.A., Rosing J. and Kemp, Jr., A. (1973) Biochim. Biophys. Acta 305, 185-198). Energization has no effect on the V value of ATP transport in sonic particles. 6. In contrast to intact mitochondria, inhibition of ADP transport in sonic particles by bongkrekic acid does not have any lag-time and does not depend on pH. The inhibition caused by bongkrekic acid is a mixed type inhibition with a Ki value of 1.2 micronM. Atractyloside and carboxyatractyloside do not inhibit ADP transport in sonic particles, unless the particles have been preloaded with these inhibitors during the sonication. 7. Palmityl-CoA added to sonic particles inhibits efficiently ADP transport. The mixed type inhibition found with palmityl-CoA has a Ki value of 1.6 micronM. 8. [3H]Bongkrekic acid binds to sonic particles readily and with high affinity. Bongkrekic acic binding to sonic particles does not depend on pH and it has a saturation plateau, corresponding approximately to 1.3 mol of site per mol of cytochrome a. The number of [3H]atracytloside binding sites is much lower (one-fifth of the bongkrekic acid). External carboxyatractyloside does not compete with [3H]bongkrekic acid for binding to sonic particles. However, when carboxyatractyloside is present inside the particles, it inhibits the binding of [3H]bongkrekic acid.

Involvement of oxygen free radicals in the respiratory uncoupling induced by free calcium and ADP-magnesium in isolated cardiac mitochondria: comparing reoxygenation in cultured cardiomyocytes.

PubMed

Meynier, Alexandra; Razik, Hafida; Cordelet, Catherine; Grégoire, Stéphane; Demaison, Luc

2003-01-01

Recently, we have observed that the simultaneous application of free calcium (fCa) and ADP-magnesium (Mg) reduced the ADP:O ratio in isolated cardiac mitochondria. The uncoupling was prevented by cyclosporin A, an inhibitor of the permeability transition pore. The purpose of this study was to know if the generation of oxygen free radicals (OFR) is involved in this phenomenon and if it occurs during reoxygenation (Reox) of cultured cardiomyocytes. Cardiac mitochondria were harvested from male Wistar rats. Respiration was assessed in two media with different fCa concentrations (0 or 0.6 microM) with palmitoylcarnitine and ADP-Mg as respiration substrates. The production of Krebs cycle intermediates (KCI) was determined. Without fCa in the medium, the mitochondria displayed a large production of citrate + isocitrate + alpha-ketoglutarate. fCa drastically reduced these KCI and promoted the accumulation of succinate. To know if OFR are involved in the respiratory uncoupling, the effect of 4OH-TEMPO (250 microM), a hydrosoluble scavenger of OFR, was tested. 4OH-TEMPO completely abolished the fCa- and ADP-Mg-induced uncoupling. Conversely, vitamin E contributed to further decreasing the ADP:O ratio. Since no hydrosoluble electron acceptor was added in our experiment, the oxygen free radical-induced oxidized vitamin E was confined near the mitochondrial membranes, which should reduce the ADP:O ratio by opening the permeability transition pore. The generation of OFR could result from the matrix accumulation of succinate. Taken together, these results indicate that mitochondrial Ca uptake induces a slight increase in membrane permeability. Thereafter, Mg enters the matrix and, in combination with Ca, stimulates the isocitrate and/or alpha-ketoglutarate dehydrogenases. Matrix succinate favors oxygen free radical generation that further increases membrane permeability and allows respiratory uncoupling through proton leakage. To determine whether the phenomenon takes place during Reox, cultured cardiomyocytes were subjected to hypoxia and Reox. 14C-palmitate was added during Reox to determine the KCI profile. Succinate had not increased during Reox. In conclusion, calcium- and ADP-Mg-induced respiratory uncoupling is due to oxygen free radical generation through excess matrix accumulation of succinate. The phenomenon does not occur during reoxygenation because of a total restoration of mitochondrial magnesium and/or ADP concentration.

Fluorescence polarization immunoassays for monitoring nucleoside triphosphate diphosphohydrolase (NTPDase) activity.

PubMed

Fiene, Amelie; Baqi, Younis; Lecka, Joanna; Sévigny, Jean; Müller, Christa E

2015-01-07

The following members of the ecto-nucleoside triphosphate diphosphohydrolase family, NTPDase1 (CD39), NTPDase-2, -3, and -8, play an important role in purinergic signal transduction by regulating extracellular nucleotide levels. Potent and selective NTPDase inhibitors are required as pharmacological tools and have potential as novel drugs, e.g. for anti-cancer and anti-bacterial therapy. We have developed fast and sensitive NTPDase fluorescence polarization (FP) immunoassays using the natural substrates (ATP or ADP). During the NTPDase1-catalyzed reaction, the substrate is dephosphorylated to ADP which is further dephosphorylated yielding AMP as the final product (by NTPDase1). NTPDase3 and -8 yield AMP and ADP, while NTPDase2 results mainly in the formation of ADP. Direct quantification of the respective product, AMP or ADP, is achieved by displacement of an appropriate fluorescent tracer nucleotide from a specific antibody leading to a change in fluorescence polarization. The assays are highly sensitive and can be performed with low substrate concentrations (20 μM ATP or 10 μM ADP) below the KM values of NTPDases, which simplifies the identification of novel competitive inhibitors. Optimized antibody and enzyme concentrations allow the reproducible detection of 2 μM ADP and 1 μM AMP (at 10% substrate conversion). Validation of the assays yielded excellent Z'-factors greater than 0.70 for all investigated NTPDase subtypes indicating high robustness of the analytical method. Furthermore, we tested a standard inhibitor and performed a first exemplary screening campaign with a library consisting of >400 compounds (Z'-factor: 0.87, hit rate 0.5%). Thereby we demonstrated the suitability of the FP assay for IC50 value determination and high-throughput screening in a 384-well format. The new FP assays were shown to be superior to current standard assays.

Comparison of body adiposity index (BAI) and BMI with estimations of % body fat in clinically severe obese women.

PubMed

Geliebter, Allan; Atalayer, Deniz; Flancbaum, Louis; Gibson, Charlisa D

2013-03-01

Body adiposity index (BAI), a new surrogate measure of body fat (hip circumference/(height(1.5) - 18)), has been proposed as an alternative to body mass index (BMI). We compared BAI with BMI, and each of them with laboratory measures of body fat-derived from bioimpedance analysis (BIA), air displacement plethysmography (ADP), and dual-energy X-ray absorptiometry (DXA) in clinically severe obese (CSO) participants. Nineteen prebariatric surgery CSO, nondiabetic women were recruited (age = 32.6 ± 7.7 SD; BMI = 46.5 ± 9.0 kg/m(2) ). Anthropometrics and body fat percentage (% fat) were determined from BIA, ADP, and DXA. Scatter plots with lines of equality and Bland-Altman plots were used to compare BAI and BMI with % fat derived from BIA, ADP, and DXA. BAI and BMI correlated highly with each other (r = 0.90, P < 0.001). Both BAI and BMI correlated significantly with % fat from BIA and ADP. BAI, however, did not correlate significantly with % fat from DXA (r = 0.42, P = 0.08) whereas BMI did (r = 0.65, P = 0.003). BMI was also the single best predictor of % fat from both BIA (r(2) = 0.80, P < 0.001) and ADP (r(2) = 0.65, P < 0.001). The regression analysis showed that the standard error of the estimate (SEE), or residual error around the regression lines, was greater for BAI comparisons than for BMI comparisons with BIA, ADP, and DXA. Consistent with this, the Bland and Altman plots indicated wider 95% confidence intervals for BAI difference comparisons than for BMI difference comparisons for their respective means for BIA, ADP, and DXA. Thus, BAI does not appear to be an appropriate proxy for BMI in CSO women. Copyright © 2012 The Obesity Society.

Air displacement plethysmography: validation in overweight and obese subjects.

PubMed

Ginde, Samir R; Geliebter, Allan; Rubiano, Frederick; Silva, Analiza M; Wang, Jack; Heshka, Stanley; Heymsfield, Steven B

2005-07-01

Patients with moderate and severe obesity, because of their physical size, often cannot be evaluated with conventional body composition measurement systems. The BOD POD air displacement plethysmography (ADP) system can accommodate a large body volume and may provide an opportunity for measuring body density (D(b)) in obese subjects. D(b) can be used in two- or three-compartment body composition models for estimating total body fat in patients with severe obesity. The purpose of this study was to compare D(b) measured by ADP to D(b) measured by underwater weighing (UWW) in subjects ranging from normal weight to severely obese. D(b) was measured with UWW and BOD POD in 123 subjects (89 men and 34 women; age, 46.5 +/- 16.9 years; BMI, 31.5 +/- 7.3 kg/m2); 15, 70, and 10 subjects were overweight (25 < or = BMI < 30 kg/m2), obese (30 < or = BMI < 40 kg/m2), and severely obese (BMI > or = 40 kg/m2), respectively. There was a strong correlation between D(b) (kilograms per liter) measured by UWW and ADP (r = 0.94, standard error of the estimate = 0.0073 kg/L, p < 0.001). Similarly, percent fat estimates from UWW and ADP using the two-compartment Siri equation were highly correlated (r = 0.94, standard error of the estimate = 3.58%, p < 0.001). Bland-Altman analysis showed no significant bias between D(b) measured by UWW and ADP. After controlling for D(b) measured by ADP, no additional between-subject variation in D(b) by UWW was accounted for by subject age, sex, or BMI. Body density, an important physical property used in human body composition models, can be accurately measured by ADP in overweight and obese subjects.

Regulation of respiration in brain mitochondria and synaptosomes: restrictions of ADP diffusion in situ, roles of tubulin, and mitochondrial creatine kinase.

PubMed

Monge, Claire; Beraud, Nathalie; Kuznetsov, Andrey V; Rostovtseva, Tatiana; Sackett, Dan; Schlattner, Uwe; Vendelin, Marko; Saks, Valdur A

2008-11-01

The role of ubiquitous mitochondrial creatine kinase (uMtCK) reaction in regulation of mitochondrial respiration was studied in purified preparations of rat brain synaptosomes and mitochondria. In permeabilized synaptosomes, apparent Km for exogenous ADP, Km (ADP), in regulation of respiration in situ was rather high (110 +/- 11 microM) in comparison with isolated brain mitochondria (9 +/- 1 microM). This apparent Km for ADP observed in isolated mitochondria in vitro dramatically increased to 169 +/- 52 microM after their incubation with 1 muM of dimeric tubulin showing that in rat brain, particularly in synaptosomes, mitochondrial outer membrane permeability for ADP, and ATP may be restricted by tubulin binding to voltage dependent anion channel (VDAC). On the other hand, in synaptosomes apparent Km (ADP) decreased to 25 +/- 1 microM in the presence of 20 mM creatine. To fully understand this effect of creatine on kinetics of respiration regulation, complete kinetic analysis of uMtCK reaction in isolated brain mitochondria was carried out. This showed that oxidative phosphorylation specifically altered only the dissociation constants for MgATP, by decreasing that from ternary complex MtCK.Cr.MgATP (K (a)) from 0.13 +/- 0.02 to 0.018 +/- 0.007 mM and that from binary complex MtCK.MgATP (K (ia)) from 1.1 +/- 0.29 mM to 0.17 +/- 0.07 mM. Apparent decrease of dissociation constants for MgATP reflects effective cycling of ATP and ADP between uMtCK and adenine nucleotide translocase (ANT). These results emphasize important role and various pathophysiological implications of the phosphocreatine-creatine kinase system in energy transfer in brain cells, including synaptosomes.

Inhibition of ATP Synthase by Chlorinated Adenosine Analogue

PubMed Central

Chen, Lisa S.; Nowak, Billie J.; Ayres, Mary L.; Krett, Nancy L.; Rosen, Steven T.; Zhang, Shuxing; Gandhi, Varsha

2009-01-01

8-Chloroadenosine (8-Cl-Ado) is a ribonucleoside analogue that is currently in clinical trial for chronic lymphocytic leukemia. Based on the decline in cellular ATP pool following 8-Cl-Ado treatment, we hypothesized that 8-Cl-ADP and 8-Cl-ATP may interfere with ATP synthase, a key enzyme in ATP production. Mitochondrial ATP synthase is composed of two major parts; FO intermembrane base and F1 domain, containing α and β subunits. Crystal structures of both α and β subunits that bind to the substrate, ADP, are known in tight binding (αdpβdp) and loose binding (αtpβtp) states. Molecular docking demonstrated that 8-Cl-ADP/8-Cl-ATP occupied similar binding modes as ADP/ATP in the tight and loose binding sites of ATP synthase, respectively, suggesting that the chlorinated nucleotide metabolites may be functional substrates and inhibitors of the enzyme. The computational predictions were consistent with our whole cell biochemical results. Oligomycin, an established pharmacological inhibitor of ATP synthase, decreased both ATP and 8-Cl-ATP formation from exogenous substrates, however, did not affect pyrimidine nucleoside analogue triphosphate accumulation. Synthesis of ATP from ADP was inhibited in cells loaded with 8-Cl-ATP. These biochemical studies are in consent with the computational modeling; in the αtpβtp state 8-Cl-ATP occupies similar binding as ANP, a non-hydrolyzable ATP mimic that is a known inhibitor. Similarly, in the substrate binding site (αdpβdp) 8-Cl-ATP occupies a similar position as ATP mimic ADP-BeF3 −. Collectively, our current work suggests that 8-Cl-ADP may serve as a substrate and the 8-Cl-ATP may be an inhibitor of ATP synthase. PMID:19477165

A rare duplication on chromosome 16p11.2 is identified in patients with psychosis in Alzheimer's disease.

PubMed

Zheng, Xiaojing; Demirci, F Yesim; Barmada, M Michael; Richardson, Gale A; Lopez, Oscar L; Sweet, Robert A; Kamboh, M Ilyas; Feingold, Eleanor

2014-01-01

Epidemiological and genetic studies suggest that schizophrenia and autism may share genetic links. Besides common single nucleotide polymorphisms, recent data suggest that some rare copy number variants (CNVs) are risk factors for both disorders. Because we have previously found that schizophrenia and psychosis in Alzheimer's disease (AD+P) share some genetic risk, we investigated whether CNVs reported in schizophrenia and autism are also linked to AD+P. We searched for CNVs associated with AD+P in 7 recurrent CNV regions that have been previously identified across autism and schizophrenia, using the Illumina HumanOmni1-Quad BeadChip. A chromosome 16p11.2 duplication CNV (chr16: 29,554,843-30,105,652) was identified in 2 of 440 AD+P subjects, but not in 136 AD subjects without psychosis, or in 593 AD subjects with intermediate psychosis status, or in 855 non-AD individuals. The frequency of this duplication CNV in AD+P (0.46%) was similar to that reported previously in schizophrenia (0.46%). This duplication CNV was further validated using the NanoString nCounter CNV Custom CodeSets. The 16p11.2 duplication has been associated with developmental delay, intellectual disability, behavioral problems, autism, schizophrenia (SCZ), and bipolar disorder. These two AD+P patients had no personal of, nor any identified family history of, SCZ, bipolar disorder and autism. To the best of our knowledge, our case report is the first suggestion that 16p11.2 duplication is also linked to AD+P. Although rare, this CNV may have an important role in the development of psychosis.

Assessment of platelet function in healthy sedated cats using three whole blood platelet function tests.

PubMed

Ho, Kimberly K; Abrams-Ogg, Anthony C G; Wood, R Darren; O'Sullivan, M Lynne; Kirby, Gordon M; Blois, Shauna L

2015-05-01

The objectives of this study were to establish feline references intervals for 3 commercial whole blood platelet function test analyzer systems: Multiplate analyzer (MP; Roche Diagnostics International Ltd., Rotkreuz, Switzerland), Platelet Function Analyzer-100 (PF: Siemens Canada, Mississauga, Ontario, Canada), and Plateletworks Combo-25 kit (PW; Helena Laboratories, Beaumont, TX). Venipuncture was performed on 55 healthy sedated cats, and platelet aggregation in response to adenosine diphosphate (ADP), collagen (COL), and arachidonic acid (AA; MP only) was assessed using citrated blood. For the MP analyzer, median (95% confidence intervals [CIs]) area under curve (Units) for ADP, COL, and AA agonists were 87 (11-176), 81 (32-129), and 91 (59-129), respectively. For the PF analyzer, median (95% CIs) closure time, using COL-ADP cartridges, was 69 (46-89) sec. For the PW assay, median (95% CIs) percent aggregations for ADP and COL agonists were 71 (18-92) and 49 (9-96), respectively, using impedance hematology analyzer platelet counts, and 94 (25-98) and 68 (14-119), respectively, using flow cytometry hematology analyzer platelet counts. There were low correlations between the PF analyzer (COL-ADP cartridge) and MP analyzer (COL agonist; ρ = 0.11), and between the PF analyzer (COL-ADP cartridge) and PW assay (COL agonist using impedance platelet counts; ρ = 0.14). The PW assay percent aggregations using impedance and flow cytometric platelet counts were correlated for both ADP (ρ = 0.64) and COL (ρ = 0.64) agonists. Platelet function testing using these tests are feasible in cats, but 95% CIs are wide, so single results may be difficult to interpret. Platelet counting by impedance or flow cytometry may be used for the PW assay but are not interchangeable. © 2015 The Author(s).

Office of Command Security Total Quality Management Plan

DTIC Science & Technology

1989-07-01

outlines the Office of Command Security instruction for TQM implementation. Keywords: TQM (Total Quality Management ), DLA Office of Command Security, Continuous process improvement, Automatic data processing security.

Evaluation of Nipah Virus as a Human and Animal Biological Terrorism and Warfare Agent

DTIC Science & Technology

2001-09-01

UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP013384 TITLE: Evaluation of Nipah Virus as a Human and Animal Biological...following component part numbers comprise the compilation report: ADP013371 thru ADP013468 UNCLASSIFIED 14. EVALUATION OF NIPAH VIRUS AS A HUMAN AND ANIMAL...of BTWC proposed including Nipah virus in the list of animal pathogens. This paper describes an evaluation of Nipah virus as a biological agent for

Hydrogen peroxide-induced injury of cells and its prevention by inhibitors of poly(ADP-ribose) polymerase.

PubMed Central

Schraufstatter, I U; Hyslop, P A; Hinshaw, D B; Spragg, R G; Sklar, L A; Cochrane, C G

1986-01-01

H2O2, in concentrations achieved in the proximity of stimulated leukocytes, induces injury and lysis of target cells. This may be an important aspect of inflammatory injury of tissues. Cell lysis in two target cells, the murine macrophage-like tumor cell line P388D1 and human peripheral lymphocytes, was found to be associated with activation of poly(ADP-ribose) polymerase (EC 2.4.2.30), a nuclear enzyme. This enzyme is activated under various conditions of DNA damage. Poly(ADP-ribose) polymerase utilizes nicotinamide adenine dinucleotide (NAD) as substrate and has been previously shown to consume NAD during exposure of cells to oxidants that was associated with inhibition of glycolysis, a decrease in cellular ATP, and cell death. In the current studies, inhibition of poly(ADP-ribose) polymerase by 3-aminobenzamide, nicotinamide, or theophylline in cells exposed to lethal concentrations of H2O2 prevented the sequence of events that eventually led to cell lysis--i.e., the decrease in NAD, followed by depletion of ATP, influx of extracellular Ca2+, actin polymerization and, finally, cell death. DNA damage, the initial stimulus for poly(ADP-ribose) polymerase activation, occurred despite the inhibition of this enzyme. Cells exposed to oxidant in the presence of the poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide failed to demonstrate repair of DNA strand breaks. PMID:2941760

Crystallization and preliminary X-ray diffraction studies of the lipopolysaccharide core biosynthetic enzyme ADP-L-glycero-D-mannoheptose 6-epimerase from Escherichia coli K-12.

PubMed

Ding, L; Zhang, Y; Deacon, A M; Ealick, S E; Ni, Y; Sun, P; Coleman, W G

1999-03-01

ADP-L-glycero-D-mannoheptose 6-epimerase is a 240 kDa NAD-dependent nucleotide diphosphosugar epimerase from Escherichia coli K12 which catalyzes the interconversion of ADP-D-glycero-D-mannoheptose and ADP-L-glycero-D-mannoheptose. ADP-L-glycero-D-mannoheptose is a required intermediate for lipopolysaccharide inner-core and outer-membrane biosynthesis in several genera of pathogenic and non-pathogenic Gram-negative bacteria. ADP-L-glycero-D-mannoheptose 6-epimerase was overexpressed in E. coli and purified to apparent homogeneity by chromatographic methods. Three crystal forms of the epimerase were obtained by a hanging-drop vapor-diffusion method. A native data set for crystal form III was collected in-house on a Rigaku R-AXIS-IIC image plate at 3.0 A resolution. The form III crystals belong to the monoclinic space group P21. The unit-cell parameters are a = 98.94, b = 110.53, c = 180.68 A and beta = 90.94 degrees. Our recent results show that these crystals diffract to 2.0 A resolution at the Cornell High Energy Synchrotron Source. The crystal probably contains six 40 kDa monomers per asymmetric unit, with a corresponding volume per protein mass (Vm) of 4.11 A3 Da-1 and a solvent fraction of 70%.

Inhibition of poly(ADP-ribose) polymerase interferes with Trypanosoma cruzi infection and proliferation of the parasite.

PubMed

Vilchez Larrea, Salomé C; Haikarainen, Teemu; Narwal, Mohit; Schlesinger, Mariana; Venkannagari, Harikanth; Flawiá, Mirtha M; Villamil, Silvia H Fernández; Lehtiö, Lari

2012-01-01

Poly(ADP-ribosylation) is a post-translational covalent modification of proteins catalyzed by a family of enzymes termed poly(ADP-ribose) polymerases (PARPs). In the human genome, 17 different genes have been identified that encode members of the PARP superfamily. Poly (ADP-ribose) metabolism plays a role in a wide range of biological processes. In Trypanosoma cruzi, PARP enzyme appears to play a role in DNA repair mechanisms and may also be involved in controlling the different phases of cell growth. Here we describe the identification of potent inhibitors for T. cruzi PARP with a fluorescence-based activity assay. The inhibitors were also tested on T. cruzi epimastigotes, showing that they reduced ADP-ribose polymer formation in vivo. Notably, the identified inhibitors are able to reduce the growth rate of T. cruzi epimastigotes. The best inhibitor, Olaparib, is effective at nanomolar concentrations, making it an efficient chemical tool for chacterization of ADP-ribose metabolism in T. cruzi. PARP inhibition also decreases drastically the amount of amastigotes but interestingly has no effect on the amount of trypomastigotes in the cell culture. Knocking down human PARP-1 decreases both the amount of amastigotes and trypomastigotes in cell culture, indicating that the effect would be mainly due to inhibition of human PARP-1. The result suggests that the inhibition of PARP could be a potential way to interfere with T. cruzi infection.

Clopidogrel (Plavix) and cardiac surgical patients: implications for platelet function monitoring and postoperative bleeding.

PubMed

Tanaka, Kenichi A; Szlam, Fania; Kelly, Andrew B; Vega, J David; Levy, Jerrold H

2004-08-01

The use of clopidogrel (Plavix), an inhibitor of adenosine diphosphate (ADP)-induced platelet aggregation, has been proven to reduce ischemic events in cardiovascular patients, but little information is available for optimal monitoring of platelet function in patients receiving the drug preoperatively. In the first part of the study we compared different testing modalities (thrombelastography (TEG), platelet aggregometry, and whole blood aggregation) to assess platelet ADP receptor inhibition. Because clopidogrel is a pro-drug, we used an in vitro model of ADP inhibition with 5'-p-fluorosulfonylbenzoyladenosine (FSBA). FSBA at final concentration of 80 microM completely inhibited platelet aggregation but had no effect on TEG maximum amplitude (MA). In the second part of the study, antiplatelet effects of clopidogrel were clinically assessed and correlated to postoperative bleeding in 18 coronary bypass surgery patients. Preoperative TEG results were normal or hypercoagulable in clopidogrel-treated patients, although platelet aggregation responses to ADP were inhibited. Clopidogrel-treated patients who underwent cardiopulmonary bypass had a high incidence (84.6%) of platelet transfusion therapy due to increased chest tube drainage. In conclusion, we have demonstrated that normal preoperative TEG-MA does not preclude clopidogrel-induced ADP receptor blockade; however, TEG can be a reliable monitor for CPB-induced platelet dysfunction related to GPIIb/IIIa. For monitoring clopidogrel, it is necessary to perform more specific platelet function tests (aggregometry or platelet count ratio) using ADP as an activator.

The Presence of ADP-Ribosylated Fe Protein of Nitrogenase in Rhodobacter capsulatus Is Correlated with Cellular Nitrogen Status

PubMed Central

Yakunin, Alexander F.; Laurinavichene, Tatyana V.; Tsygankov, Anatoly A.; Hallenbeck, Patrick C.

1999-01-01

The photosynthetic bacterium Rhodobacter capsulatus has been shown to regulate its nitrogenase by covalent modification via the reversible ADP-ribosylation of Fe protein in response to darkness or the addition of external NH4+. Here we demonstrate the presence of ADP-ribosylated Fe protein under a variety of steady-state growth conditions. We examined the modification of Fe protein and nitrogenase activity under three different growth conditions that establish different levels of cellular nitrogen: batch growth with limiting NH4+, where the nitrogen status is externally controlled; batch growth on relatively poor nitrogen sources, where the nitrogen status is internally controlled by assimilatory processes; and continuous culture. When cultures were grown to stationary phase with different limiting concentrations of NH4+, the ADP-ribosylation state of Fe protein was found to correlate with cellular nitrogen status. Additionally, actively growing cultures (grown with N2 or glutamate), which had an intermediate cellular nitrogen status, contained a portion of their Fe protein in the modified state. The correlation between cellular nitrogen status and ADP-ribosylation state was corroborated with continuous cultures grown under various degrees of nitrogen limitation. These results show that in R. capsulatus the modification system that ADP-ribosylates nitrogenase in the short term in response to abrupt changes in the environment is also capable of modifying nitrogenase in accordance with long-term cellular conditions. PMID:10094674

Enzymatic cycling method using creatine kinase to measure creatine by real-time detection.

PubMed

Ueda, Shigeru; Sakasegawa, Shin-Ichi

2016-08-01

We have developed a novel enzymatic cycling method that uses creatine kinase (CK) to measure creatine. The method takes advantage of the reversibility of the CK reaction in which the forward (creatine phosphate forming) and reverse reactions are catalyzed in the presence of an excess amount of ATP and IDP, respectively. Real-time detection was accomplished using ADP-dependent glucokinase (ADP-GK) together with glucose-6-phosphate dehydrogenase. ADP, one of the cycling reaction products, was distinguished from IDP by using the nucleotide selectivity of the ADP-GK. The increasing level of ADP was measured from the level of reduced NADP at 340 nm. The method is appropriate for an assay that requires high sensitivity because the rate of increase in absorbance at 340 nm is proportional to the amount of CK present in the reaction mix. We reasoned that the method with CK in combination with creatinine amidohydrolase could be used to assay creatinine, an important marker of kidney function. Our results confirmed the quantitative capability of the assay. Copyright © 2016 Elsevier Inc. All rights reserved.

Apoptosis induction in prostate cancer cells by a novel gene product, pHyde, involves caspase-3.

PubMed

Zhang, X; Steiner, M S; Rinaldy, A; Lu, Y

2001-09-20

A novel gene, pHyde, was recently cloned from Dunning rat prostate cancer cells. A recombinant adenovirus containing pHyde cDNA gene (AdpHyde) was generated to investigate the biological function of pHyde protein. AdpHyde inhibited the growth of human prostate cancer cells. Apoptosis was induced in AdpHyde transduced cells as demonstrated by DAPI (4', 6-diamino-2-phenylindole), TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling) staining, and flow cytometry assays. Apoptosis was also induced in human xenograft prostate cancer tumors growing in nude mice following treatment with AdpHyde. AdpHyde transduction resulted in a dose-dependent stimulation of caspase-3 activity in DU145 cells which was blocked by DEVD (succinyl-Asp-Glu-Val-Asp-aldehyde) and VAD (benzyloxycarbonyl - Val - Ala - Asp -fluoromethylketone), inhibitors specifically against caspase-3. Moreover, cancer cells that lacked expression of endogenous caspase-3 were not or barely inhibited by pHyde. These results taken together suggest that pHyde inhibits cancer growth by inducing apoptosis through a caspase-3 dependent pathway.

Mitochondrial respiratory control is lost during growth factor deprivation

PubMed Central

Gottlieb, Eyal; Armour, Sean M.; Thompson, Craig B.

2002-01-01

The ability of cells to maintain a bioenergetically favorable ATP/ADP ratio confers a tight balance between cellular events that consume ATP and the rate of ATP production. However, after growth factor withdrawal, the cellular ATP/ADP ratio declines. To investigate these changes, mitochondria from growth factor-deprived cells isolated before the onset of apoptosis were characterized in vitro. Mitochondria from growth factor-deprived cells have lost their ability to undergo matrix condensation in response to ADP, which is accompanied by a failure to perform ADP-coupled respiration. At the time of analysis, mitochondria from growth factor-deprived cells were not depleted of cytochrome c and cytochrome c-dependent respiration was unaffected, demonstrating that the inhibition of the respiratory rate is not due to loss of cytochrome c. Agents that disrupt the mitochondrial outer membrane, such as digitonin, or maintain outer membrane exchange of adenine nucleotide, such as Bcl-xL, restored ADP-dependent control of mitochondrial respiration. Together, these data suggest that the regulation of mitochondrial outer membrane permeability contributes to respiratory control. PMID:12228733

Data-Driven Zero-Sum Neuro-Optimal Control for a Class of Continuous-Time Unknown Nonlinear Systems With Disturbance Using ADP.

PubMed

Wei, Qinglai; Song, Ruizhuo; Yan, Pengfei

2016-02-01

This paper is concerned with a new data-driven zero-sum neuro-optimal control problem for continuous-time unknown nonlinear systems with disturbance. According to the input-output data of the nonlinear system, an effective recurrent neural network is introduced to reconstruct the dynamics of the nonlinear system. Considering the system disturbance as a control input, a two-player zero-sum optimal control problem is established. Adaptive dynamic programming (ADP) is developed to obtain the optimal control under the worst case of the disturbance. Three single-layer neural networks, including one critic and two action networks, are employed to approximate the performance index function, the optimal control law, and the disturbance, respectively, for facilitating the implementation of the ADP method. Convergence properties of the ADP method are developed to show that the system state will converge to a finite neighborhood of the equilibrium. The weight matrices of the critic and the two action networks are also convergent to finite neighborhoods of their optimal ones. Finally, the simulation results will show the effectiveness of the developed data-driven ADP methods.

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

Sun, Linlin; Sun, Xiaodong; Xie, Songbo

Highlights: • DIMEN displays higher anti-proliferative activity than enastron. • DIMEN induced mitotic arrest and apoptosis more significantly than enastron. • DIMEN blocked the conformational change of ADP-binding pocket more effectively. • DIMEN hindered ADP release more potently than enastron. - Abstract: Eg5 is a mitotic kinesin that plays a crucial role in the formation of bipolar mitotic spindles, by hydrolyzing ATP to push apart anti-parallel microtubules. Dimethylenastron is potent specific small molecule inhibitor of Eg5. The mechanism by which dimethylenastron inhibits Eg5 function remains unclear. By comparing with enastron, here we report that dimethylenastron prevents the growth of pancreaticmore » and lung cancer cells more effectively, by halting mitotic progression and triggering apoptosis. We analyze their interactions with ADP-bound Eg5 crystal structure, and find that dimethylenastron binds Eg5 motor domain with higher affinity. In addition, dimethylenastron allosterically blocks the conformational change of the “sandwich”-like ADP-binding pocket more effectively. We subsequently use biochemical approach to reveal that dimethylenastron slows ADP release more significantly than enastron. These data thus provide biological, structural and mechanistic insights into the potent inhibitory activity of dimethylenastron.« less

Secure environment for real-time tele-collaboration on virtual simulation of radiation treatment planning.

PubMed

Ntasis, Efthymios; Maniatis, Theofanis A; Nikita, Konstantina S

2003-01-01

A secure framework is described for real-time tele-collaboration on Virtual Simulation procedure of Radiation Treatment Planning. An integrated approach is followed clustering the security issues faced by the system into organizational issues, security issues over the LAN and security issues over the LAN-to-LAN connection. The design and the implementation of the security services are performed according to the identified security requirements, along with the need for real time communication between the collaborating health care professionals. A detailed description of the implementation is given, presenting a solution, which can directly be tailored to other tele-collaboration services in the field of health care. The pilot study of the proposed security components proves the feasibility of the secure environment, and the consistency with the high performance demands of the application.

A Sustainable WMD Nonproliferation Strategy for East Africa: Connecting the WMD Nonproliferation Agenda with Local Border Security Needs to Achieve Mutually Beneficial Outcomes

DTIC Science & Technology

2014-01-01

Government of Kenya stakeholders with providing a framework for analysis by engaging with a wide range of border security experts from key donor states...holistic national border security action plan and gap analysis were necessary to simultaneously deal with the global WMD nonproliferation agenda and...efforts from a research and analysis vantage point. The underlying idea was that Kenya, through this border security action plan and gap analysis , would

Signaling Mechanism of Poly(ADP-Ribose) Polymerase-1 (PARP-1) in Inflammatory Diseases

PubMed Central

Ba, Xueqing; Garg, Nisha Jain

2011-01-01

Poly(ADP-ribosyl)ation, attaching the ADP-ribose polymer chain to the receptor protein, is a unique posttranslational modification. Poly(ADP-ribose) polymerase-1 (PARP-1) is a well-characterized member of the PARP family. In this review, we provide a general update on molecular structure and structure-based activity of this enzyme. However, we mainly focus on the roles of PARP-1 in inflammatory diseases. Specifically, we discuss the signaling pathway context that PARP-1 is involved in to regulate the pathogenesis of inflammation. PARP-1 facilitates diverse inflammatory responses by promoting inflammation-relevant gene expression, such as cytokines, oxidation-reduction–related enzymes, and adhesion molecules. Excessive activation of PARP-1 induces mitochondria-associated cell death in injured tissues and constitutes another mechanism for exacerbating inflammation. PMID:21356345

Bacillus cereus Certhrax ADP-ribosylates Vinculin to Disrupt Focal Adhesion Complexes and Cell Adhesion*

PubMed Central

Simon, Nathan C.; Barbieri, Joseph T.

2014-01-01

Bacillus cereus is often associated with mild to moderate gastroenteritis; however, some recent isolates cause inhalational anthrax-like diseases and death. These potential emerging human pathogens express multiple virulence factors. B. cereus strain G9241 expresses anthrax toxin, several polysaccharide capsules, and the novel ADP-ribosyltransferase, Certhrax. In this study, we show that Certhrax ADP-ribosylates Arg-433 of vinculin, a protein that coordinates actin cytoskeleton and extracellular matrix interactions. ADP-ribosylation of vinculin disrupted focal adhesion complexes and redistributed vinculin to the cytoplasm. Exogenous vinculin rescued these phenotypes. This provides a mechanism for strain G9241 to breach host barrier defenses and promote bacterial growth and spread. Certhrax is the first bacterial toxin to add a post-translational modification to vinculin to disrupt the actin cytoskeleton. PMID:24573681

National Security Technology Incubation Strategic Plan

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

None, None

This strategic plan contains information on the vision, mission, business and technology environment, goals, objectives, and incubation process of the National Security Technology Incubation Program (NSTI) at Arrowhead Center. The development of the NSTI is a key goal of the National Security Preparedness Project (NSPP). Objectives to achieve this goal include developing incubator plans (strategic, business, action, and operations), creating an incubator environment, creating a support and mentor network for companies in the incubator program, attracting security technology businesses to the region, encouraging existing business to expand, initiating business start-ups, evaluating products and processes of the incubator program, and achievingmore » sustainability of the incubator program. With the events of 9/11, the global community faces ever increasing and emerging threats from hostile groups determined to rule by terror. According to the National Nuclear Security Administration (NNSA) Strategic Plan, the United States must be able to quickly respond and adapt to unanticipated situations as they relate to protection of our homeland and national security. Technology plays a key role in a strong national security position, and the private business community, along with the national laboratories, academia, defense and homeland security organizations, provide this technology. Fostering innovative ideas, translated into relevant technologies answering the needs of NNSA, is the purpose of the NSTI. Arrowhead Center of New Mexico State University is the operator and manager of the NSTI. To develop the NSTI, Arrowhead Center must meet the planning, development, execution, evaluation, and sustainability activities for the program and identify and incubate new technologies to assist the NNSA in meeting its mission and goals. Technology alone does not give a competitive advantage to the country, but the creativity and speed with which it is employed does. For a company to succeed, it must have sustainable competitive advantages in seven key areas: geography, products and businesses, distribution, sales and service culture, efficiency, brand, and most important, people. The four strategic goals of the plan are to: 1. Identify and recruit small businesses with technology applications for national security. 2. Design and implement a national security incubator program that provides incubator services and physical space for the targeted businesses. 3. Provide business assistance and technical leadership to NSTI clients to assist in bringing their products to market. 4. Construct a new multi-tenant facility with dedicated physical space for businesses with technology applications for national security.« less

The public transportation system security and emergency preparedness planning guide

DOT National Transportation Integrated Search

2003-01-01

Recent events have focused renewed attention on the vulnerability of the nation's critical infrastructure to major events, including terrorism. The Public Transportation System Security and Emergency Preparedness Planning Guide has been prepared to s...

9. Photocopy of engineering drawing. SECURITY UPGRADES, SLC17: PLANS, SECTIONS, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

9. Photocopy of engineering drawing. SECURITY UPGRADES, SLC17: PLANS, SECTIONS, AND DETAILS, JANUARY 1993. - Cape Canaveral Air Station, Launch Complex 17, Facility 28425, East end of Lighthouse Road, Cape Canaveral, Brevard County, FL

44 CFR 334.2 - Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., each Federal department and agency shall prepare its national security emergency preparedness plans and... preparedness plans and programs to provide appropriate and effective response options for consideration in... Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY...

Plan Nacional de Desarrollo y Seguridad 1971-1975 (National Plan for Development and Security, 1971-1975).

ERIC Educational Resources Information Center

Boletin del Centro Nacional de Documentacion e Informacion Educativa, 1971

1971-01-01

This article discusses the education provisions established in the Argentine Plan for Development and Security (1971-1975). The statements on educational development call for a diagnostic study of the current cultural and educational situation, the establishment of objectives and strategies, goals for each level of education, steps for the…

The Role of Simultaneous Counternarcotics and Counterterrorism Operations in the Afghan Coin Model

DTIC Science & Technology

2014-05-22

COIN model, which was developed through Plan Colombia and the security policies of Alvaro Uribe to target terrorists and narco-traffickers...theory by examining the Colombian COIN model, which was developed through Plan Colombia and the security policies of Alvaro Uribe to target terrorists...28 Plan Colombia and Alvaro Uribe .............................................................................................. 32

An ADPE Protest Primer: Lessons Learned from GSBCA Protest Decisions

DTIC Science & Technology

1991-06-01

reverse if necessary and identify, by block number) The General services Administration’s Board of Contract Appeals (GSBCA) is a significant venue for...David R. Whipple,i D ep a rtm en t of A d i i t a i eS ci ce iim ABSTRACT The General Services Administration’s Board of Contract Appeals (GSBCA) is a...Administration Board of Contract Appeals (GSBCA) ADPE protest decisions. In effect this study will serve as a primer to familiarize new Federal ADPE

Recruiting and Selection in the French Army (Recrutement et Selection Dans L’Armee Francaise)

DTIC Science & Technology

2000-08-01

UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP010377 TITLE: Recruiting and Selection in the French Army [Recrutement...ADP010347 thru ADP010377 UNCLASSIFIED 29-1 RECRUTEMENT ET SELECTION DANS L’ARMEE FRANCAISE RECRUITING AND SELECTION IN THE FRENCH ARMY Colonel Stiphane...LAGACHE DPMAT/Bureau Evaluation 93, boulevard du Montparnasse BP 328 - 75006 PARIS, France T6l6phone : +33 (0)1.53.71.03.10 - Fax +33 (0)1.53.71.03.12

Differential effect of silybin on the Fe2+-ADP and t-butyl hydroperoxide-induced microsomal lipid peroxidation.

PubMed

Valenzuela, A; Guerra, R

1986-02-15

We have observed a differential effect of silybin dihemisuccinate on rat liver microsomal oxygen consumption and on lipid peroxidation induced by NADPH-Fe2+-ADP and t-butyl hydroperoxide. These results are ascribed to the antioxidant properties of the flavonoid. The differences observed in the effect of the catalysts may be a consequence of the different capacity of silybin to act as a scavenger of free radicals formed by NADPH-Fe2+-ADP or t-butyl hydroperoxide.

Using Computer Models to Identify Common Therapeutic Targets in Host Adapted Bacterial Threat Agents

DTIC Science & Technology

2011-08-01

tetraphosphatase[c]  :   ap4a  +   2o  -­‐-­‐>  (2)  adp  +  (2)  hNucleo d  Salvage  Pathways Nucleo(deBMA_1991 ApaH EC...tetraphosphatase[c] : ap4a + h2o --> (2) adp + (2) h BPSL2687 ApaH AP5AH Ap5A hydrolase [c] : ap5a + h2o --> adp + atp + (2) h BPSL2687 ApaH CSND Cytosine deaminase

Planning for Post-Regime Change Environments: The Introduction of a Post-Regime Environment Planning Partnership (PREPP)

DTIC Science & Technology

2016-05-26

makers. The third case study, on Nigeria , will provide an analysis of a peaceful transition of power. Finally, the structure for a proposed Post...15. SUBJECT TERMS Regime Change, National Security Council, Kosovo, Libya, Nigeria , transition of power, post-regime change planning. 16. SECURITY...conflation that exists between the planning element and politically appointed decision makers. The third case study, on Nigeria , will provide an analysis of

Kinetic competence of the cADP-ribose-CD38 complex as an intermediate in the CD38/NAD+ glycohydrolase-catalysed reactions: implication for CD38 signalling.

PubMed Central

Cakir-Kiefer, C; Muller-Steffner, H; Oppenheimer, N; Schuber, F

2001-01-01

CD38/NAD(+) glycohydrolase is a type II transmembrane glycoprotein widely used to study T- and B-cell activation and differentiation. CD38 is endowed with two different activities: it is a signal transduction molecule and an ectoenzyme that converts NAD(+) into ADP-ribose (NAD(+) glycohydrolase activity) and small proportions of cADP-ribose (cADPR; ADP-ribosyl cyclase activity), a calcium-mobilizing metabolite, which, ultimately, can also be hydrolysed (cADPR hydrolase activity). The relationship between these two properties, and strikingly the requirement for signalling in the formation of free or enzyme-complexed cADPR, is still ill-defined. In the present study we wanted to test whether the CD38-cADPR complex is kinetically competent in the conversion of NAD(+) into the reaction product ADP-ribose. In principle, such a complex could be invoked for cross-talk, via conformational changes, with neighbouring partner(s) of CD38 thus triggering the signalling phenomena. Analysis of the kinetic parameters measured for the CD38/NAD(+) glycohydrolase-catalysed hydrolysis of 2'-deoxy-2'-aminoribo-NAD(+) and ADP-cyclo[N1,C1']-2'-deoxy-2'-aminoribose (slowly hydrolysable analogues of NAD(+) and cADPR respectively) ruled out that the CD38-cADPR complex can accumulate under steady-state conditions. This was borne out by simulation of the prevalent kinetic mechanism of CD38, which involve the partitioning of a common E.ADP-ribosyl intermediate in the formation of the enzyme-catalysed reaction products. Using this mechanism, microscopic rate conditions were found which transform a NAD(+) glycohydrolase into an ADP-ribosyl cyclase. Altogether, the present work shows that if the cross-talk with a partner depends on a conformational change of CD38, this is most probably not attributable to the formation of the CD38-cADPR complex. In line with recent results on the conformational change triggered by CD38 ligands [Berthelier, Laboureau, Boulla, Schuber and Deterre (2000) Eur. J. Biochem. 267, 3056-3064], we believe that the Michaelis CD38-NAD(+) complex could play such a role instead. PMID:11513738

A novel diagnostic protocol to identify patients suitable for discharge after a single high-sensitivity troponin

PubMed Central

Carlton, Edward W; Cullen, Louise; Than, Martin; Gamble, James; Khattab, Ahmed; Greaves, Kim

2015-01-01

Objective To establish whether a novel accelerated diagnostic protocol (ADP) for suspected acute coronary syndrome (ACS) could successfully identify low-risk patients suitable for discharge after a single high-sensitivity troponin T (hs-cTnT) taken at presentation to the emergency department. We also compared the diagnostic accuracy of this ADP with strategies using initial undetectable hs-cTnT. Methods This prospective observational study evaluated the ability of the Triage Rule-out Using high-Sensitivity Troponin (TRUST) ADP to identify low-risk patients with suspected ACS. The ADP incorporated a single presentation hs-cTnT of <14 ng/L, a non-ischaemic ECG and a modified Goldman risk score. Diagnostic performance of the ADP was compared with the detection limit cut-offs of hs-cTnT (<5 ng/L and <3 ng/L). The primary end point was fatal/non-fatal acute myocardial infarction (AMI) within 30 days. Results 960 participants were recruited, mean age 58.0 years, 80 (8.3%) had an AMI. The TRUST ADP classified 382 (39.8%) as low-risk with a sensitivity for identifying AMI of 98.8% (95% CI 92.5% to 99.9%). hs-cTnT detection limits (<5 ng/L and <3 ng/L) had a sensitivity of 100% (94.3 to 100) and 100% (94.4 to 100), respectively. The TRUST ADP identified more patients suitable for early discharge at 39.8% vs 29.3% (<5 ng/L) and 7.9% (<3 ng/L) (p<0.001) with a lower false-positive rate for AMI detection; specificity 43.3% (95% CI 42.7% to 43.4%) vs 32.0% (95% CI 31.5% to 32.0%) and 8.6% (95% CI 8.1% to 8.6%), respectively. Conclusions The TRUST ADP, which incorporates structured risk-assessment and a single presentation hs-cTnT blood draw, has potential to allow early discharge in 40% of patients with suspected ACS and has greater clinical utility than undetectable hs-cTnT strategies. Trial registration number ISRCTN No. 21109279. PMID:25691511

Marketing Plan for the National Security Technology Incubator

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

None

This marketing plan was developed as part of the National Security Preparedness Project by the Arrowhead Center of New Mexico State University. The vision of the National Security Technology Incubator program is to be a successful incubator of technologies and private enterprise that assist the NNSA in meeting new challenges in national safety and security. The plan defines important aspects of developing the incubator, such as defining the target market, marketing goals, and creating strategies to reach the target market while meeting those goals. The three main marketing goals of the incubator are: 1) developing marketing materials for the incubatormore » program; 2) attracting businesses to become incubator participants; and 3) increasing name recognition of the incubator program on a national level.« less

Risk Unbound: Threat, Catastrophe, and the End of Homeland Security

DTIC Science & Technology

2015-09-01

Defense (DOD) models ) is now the prevalent model for developing plans.63 Capabilities- based within the national preparedness system is defined as...capabilities- based planning is the accounting for scenarios through organizational capability development , and the search for commonality and structure...of providing perfect security, and demonstrate the limitations of risk- based security practices. This thesis presents an argument in three parts

Homeland Security Strategic Research Action Plan 2012 - 2016

EPA Pesticide Factsheets

EPA’s Homeland Security research plan outline and how it will address science and technological gaps and improve the Agency’s ability to carry out its responsibilities associated with preparing for and responding to, terrorist attacks, and other disasters.

77 FR 70483 - Request for Comments (RFC)-Federal Cybersecurity Research and Development Strategic Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... received by December 19, 2012. SUMMARY: This Request For Comments (RFC) is issued by the Cyber Security and... plan was developed under the leadership of the Cyber Security and Information Assurance Research and...

75 FR 65526 - National Industrial Security Program Policy Advisory Committee (NISPPAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

... NATIONAL ARCHIVES AND RECORDS ADMINISTRATION Information Security Oversight Office National Industrial Security Program Policy Advisory Committee (NISPPAC) AGENCY: Information Security Oversight Office... planning to attend must be submitted to the Information Security Oversight Office (ISOO) no later than...

76 FR 6636 - National Industrial Security Program Policy Advisory Committee (NISPPAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-07

... NATIONAL ARCHIVES AND RECORDS ADMINISTRATION Information Security Oversight Office National Industrial Security Program Policy Advisory Committee (NISPPAC) AGENCY: Information Security Oversight Office... planning to attend must be submitted to the Information Security Oversight Office (ISOO) no later than...

76 FR 28099 - National Industrial Security Program Policy Advisory Committee (NISPPAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... NATIONAL ARCHIVES AND RECORDS ADMINISTRATION Information Security Oversight Office National Industrial Security Program Policy Advisory Committee (NISPPAC) AGENCY: Information Security Oversight Office... telephone number of individuals planning to attend must be submitted to the Information Security Oversight...

75 FR 39582 - National Industrial Security Program Policy Advisory Committee (NISPPAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-09

... NATIONAL ARCHIVES AND RECORDS ADMINISTRATION Information Security Oversight Office National Industrial Security Program Policy Advisory Committee (NISPPAC) AGENCY: Information Security Oversight Office... telephone number of individuals planning to attend must be submitted to the Information Security Oversight...

17 CFR 240.17a-6 - Right of national securities exchange, national securities association, registered clearing...

Code of Federal Regulations, 2010 CFR

2010-04-01

... plan may provide that any such document may be transferred to microfilm or other recording medium after... years or at such earlier date as is specified in a plan for the destruction or disposition of any such documents if such plan has been filed with the Commission by such exchange, association, clearing agency or...

41 CFR 102-192.75 - Why must we have written security policies and plans?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Why must we have written security policies and plans? 102-192.75 Section 102-192.75 Public Contracts and Property Management Federal... terrorist attacks, and this is spelled out in the Postal and Shipping Sector Plan, which is part of the...

75 FR 68009 - Office of New Reactors; Notice of Availability of the Final Staff Guidance Standard Review Plan...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-04

... the Final Staff Guidance Standard Review Plan Section 13.6.3, Revision 1 on Physical Security--Early... NRC is issuing its Final Revision 1 to NUREG-0800, ``Standard Review Plan (SRP) for the Review of Safety Analysis Reports for Nuclear Power Plants,'' Section 13.6.3, Revision 1 on Physical Security...

75 FR 68009 - Office of New Reactors; Notice of Availability of the Final Staff Guidance Standard Review Plan...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-04

... the Final Staff Guidance Standard Review Plan Section 13.6.2, Revision 1 on Physical Security--Design... issuing its Final Revision 1 to NUREG-0800, ``Standard Review Plan (SRP) for the Review of Safety Analysis Reports for Nuclear Power Plants,'' Section 13.6.2, Revision 1 on Physical Security--Design Certification...

Preliminary crystallographic analysis of ADP-glucose pyrophosphorylase from Agrobacterium tumefaciens

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

Cupp-Vickery, Jill R., E-mail: jvickery@uci.edu; Igarashi, Robert Y.; Meyer, Christopher R.

2005-03-01

Crystallization and X-ray diffraction methods for native A. tumefaciens ADP-glucose pyrophosphorylase and its selenomethionyl derivative are described. Two crystal forms are identified, both of which diffract to 2 Å.

Comparison of bioluminescent kinase assays using substrate depletion and product formation.

PubMed

Tanega, Cordelle; Shen, Min; Mott, Bryan T; Thomas, Craig J; MacArthur, Ryan; Inglese, James; Auld, Douglas S

2009-12-01

Assays for ATPases have been enabled for high-throughput screening (HTS) by employing firefly luciferase to detect the remaining ATP in the assay. However, for any enzyme assay, measurement of product formation is a more sensitive assay design. Recently, technologies that allow detection of the ADP product from ATPase reactions have been described using fluorescent methods of detection. We describe here the characterization of a bioluminescent assay that employs firefly luciferase in a coupled-enzyme assay format to enable detection of ADP levels from ATPase assays (ADP-Glo, Promega Corp.). We determined the performance of the ADP-Glo assay in 1,536-well microtiter plates using the protein kinase Clk4 and a 1,352 member kinase focused combinatorial library. The ADP-Glo assay was compared to the Clk4 assay performed using a bioluminescence ATP-depletion format (Kinase-Glo, Promega Corp). We performed this analysis using quantitative HTS (qHTS) where we determined potency values for all library members and identified approximately 300 compounds with potencies ranging from as low as 50 nM to >10 microM, yielding a robust dataset for the comparison. Both assay formats showed high performance (Z'-factors approximately 0.9) and showed a similar potency distribution for the actives. We conclude that the bioluminescence ADP detection assay system is a viable generic alternative to the widely used ATP-depletion assay for ATPases and discuss the advantages and disadvantages of both approaches.

Self-report assessment of the DSM-IV personality disorders. Measurement of trait and distress characteristics: the ADP-IV.

PubMed

Schotte, C K; de Doncker, D; Vankerckhoven, C; Vertommen, H; Cosyns, P

1998-09-01

Self-report instruments assessing the DSM personality disorders are characterized by overdiagnosis due to their emphasis on the measurement of personality traits rather than the impairment and distress associated with the criteria. The ADP-IV, a Dutch questionnaire, introduces an alternative assessment method: each test item assesses 'Trait' as well as 'Distress/impairment' characteristics of a DSM-IV criterion. This item format allows dimensional as well as categorical diagnostic evaluations. The present study explores the validity of the ADP-IV in a sample of 659 subjects of the Flemish population. The dimensional personality disorder subscales, measuring Trait characteristics, are internally consistent and display a good concurrent validity with the Wisconsin Personality Disorders Inventory. Factor analysis at the item-level resulted in 11 orthogonal factors, describing personality dimensions such as psychopathy, social anxiety and avoidance, negative affect and self-image. Factor analysis at the subscale-level identified two basic dimensions, reflecting hostile (DSM-IV Cluster B) and anxious (DSM-IV Cluster C) interpersonal attitudes. Categorical ADP-IV diagnoses are obtained using scoring algorithms, which emphasize the Trait or the Distress concepts in the diagnostic evaluation. Prevalences of ADP-IV diagnoses of any personality disorder according to these algorithms vary between 2.28 and 20.64%. Although further research in clinical samples is required, the present results support the validity of the ADP-IV and the potential of the measurement of trait and distress characteristics as a method for assessing personality pathology.

Endogenous ADP-ribosylation of elongation factor 2 in polyoma virus-transformed baby hamster kidney cells

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

Fendrick, J.L.; Iglewski, W.J.

1989-01-01

Polyoma virus-transformed baby hamster kidney (pyBHK) cells were cultured in medium containing ({sup 32}P)orthophosphate and 105 (vol/vol) fetal bovine serum. A {sup 32}P-labeled protein with an apparent molecular mass of 97 kDa was immunoprecipitated from cell lysates with antiserum to ADP-ribosylated elongation factor 2 (EF-2). The {sup 32}P labeling of the protein was enhanced by culturing cells in medium containing 2% serum instead of 10% serum. The {sup 32}P label was completely removed from the protein by treatment with snake venom phosphodiesterase and the digestion product was identified as ({sup 32}P)AMP, indicating the protein was mono-ADP-ribosylated. HPLC analysis of trypticmore » peptides of the {sup 32}P-labeled 97-kDa protein and purified EF-2, which was ADP-ribosylated in vitro with diphtheria toxin fragment A and ({sup 32}P)NAD, demonstrated an identical labeled peptide in the two proteins. The data strongly suggest that EF-2 was endogenously ADP-ribosylated in pyBHK cells. Maximum incorporation of radioactivity in EF-2 occurred by 12 hr and remained constant over the subsequent 12 hr. It was estimated that 30-35% of the EF-2 was ADP-ribosylated in cells cultured in medium containing 2% serum. When {sup 32}P-labeled cultures were incubated in medium containing unlabeled phosphate, the {sup 32}P label was lost from the EF-2 within 30 min.« less

Nucleotide-dependent conformational states of actin

PubMed Central

Pfaendtner, Jim; Branduardi, Davide; Parrinello, Michele; Pollard, Thomas D.; Voth, Gregory A.

2009-01-01

The influence of the state of the bound nucleotide (ATP, ADP-Pi, or ADP) on the conformational free-energy landscape of actin is investigated. Nucleotide-dependent folding of the DNase-I binding (DB) loop in monomeric actin and the actin trimer is carried out using all-atom molecular dynamics (MD) calculations accelerated with a multiscale implementation of the metadynamics algorithm. Additionally, an investigation of the opening and closing of the actin nucleotide binding cleft is performed. Nucleotide-dependent free-energy profiles for all of these conformational changes are calculated within the framework of metadynamics. We find that in ADP-bound monomer, the folded and unfolded states of the DB loop have similar relative free-energy. This result helps explain the experimental difficulty in obtaining an ordered crystal structure for this region of monomeric actin. However, we find that in the ADP-bound actin trimer, the folded DB loop is stable and in a free-energy minimum. It is also demonstrated that the nucleotide binding cleft favors a closed conformation for the bound nucleotide in the ATP and ADP-Pi states, whereas the ADP state favors an open confirmation, both in the monomer and trimer. These results suggest a mechanism of allosteric interactions between the nucleotide binding cleft and the DB loop. This behavior is confirmed by an additional simulation that shows the folding free-energy as a function of the nucleotide cleft width, which demonstrates that the barrier for folding changes significantly depending on the value of the cleft width. PMID:19620726

NADP/sup +/ enhances cholera and pertussis toxin-catalyzed ADP-ribosylation of membrane proteins

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

Kawai, Y.; Whitsel, C.; Arinze, I.J.

1986-05-01

Cholera or pertussis toxin-catalyzed (/sup 32/P)ADP-ribosylation is frequently used to estimate the concentration of the stimulatory (Ns) or inhibitory (Ni) guanine nucleotide regulatory proteins which modulate the activity of adenylate cyclase. With this assay, however, the degradation of the substrate, NAD/sup +/, by endogenous enzymes such as NAD/sup +/-glycohydrolase (NADase) present in the test membranes can influence the results. In this study the authors show that both cholera and pertussis toxin-catalyzed (/sup 32/P)ADP-ribosylation of liver membrane proteins is markedly enhanced by NADP/sup +/. The effect is concentration dependent; with 20 ..mu..M (/sup 32/P)NAD/sup +/ as substrate maximal enhancement is obtainedmore » at 0.5-1.0 mM NADP/sup +/. The enhancement of (/sup 32/P)ADP-ribosylation by NADP/sup +/ was much greater than that by other known effectors such as Mg/sup 2 +/, phosphate or isoniazid. The effect of NADP/sup +/ on ADP-ribosylation may occur by inhibition of the degradation of NAD/sup +/ probably by acting as an alternate substrate for NADase. Among inhibitors tested (NADP/sup +/, isoniazid, imidazole, nicotinamide, L-Arg-methyl-ester and HgCl/sub 2/) to suppress NADase activity, NADP/sup +/ was the most effective and, 10 mM, inhibited activity of the enzyme by about 90%. In membranes which contain substantial activities of NADase the inclusion of NADP/sup +/ in the assay is necessary to obtain maximal ADP-ribosylation.« less

A Study of Platelet Inhibition, Using a 'Point of Care' Platelet Function Test, following Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction [PINPOINT-PPCI].

PubMed

Johnson, Thomas W; Mumford, Andrew D; Scott, Lauren J; Mundell, Stuart; Butler, Mark; Strange, Julian W; Rogers, Chris A; Reeves, Barnaby C; Baumbach, Andreas

2015-01-01

Rapid coronary recanalization following ST-elevation myocardial infarction (STEMI) requires effective anti-platelet and anti-thrombotic therapies. This study tested the impact of door to end of procedure ('door-to-end') time and baseline platelet activity on platelet inhibition within 24hours post-STEMI. 108 patients, treated with prasugrel and procedural bivalirudin, underwent Multiplate® platelet function testing at baseline, 0, 1, 2 and 24hours post-procedure. Major adverse cardiac events (MACE), bleeding and stent thrombosis (ST) were recorded. Baseline ADP activity was high (88.3U [71.8-109.0]), procedural time and consequently bivalirudin infusion duration were short (median door-to-end time 55minutes [40-70] and infusion duration 30minutes [20-42]). Baseline ADP was observed to influence all subsequent measurements of ADP activity, whereas door-to-end time only influenced ADP immediately post-procedure. High residual platelet reactivity (HRPR ADP>46.8U) was observed in 75% of patients immediately post-procedure and persisted in 24% of patients at 2hours. Five patients suffered in-hospital MACE (4.6%). Acute ST occurred in 4 patients, all were <120mins post-procedure and had HRPR. No significant bleeding was observed. In a post-hoc analysis, pre-procedural morphine use was associated with significantly higher ADP activity following intervention. Baseline platelet function, time to STEMI treatment and opiate use all significantly influence immediate post-procedural platelet activity.

Reciprocal regulation of platelet responses to P2Y and thromboxane receptor activation.

PubMed

Barton, J F; Hardy, A R; Poole, A W; Mundell, S J

2008-03-01

Thromboxane A(2) and ADP are two major platelet agonists that stimulate two sets of G protein-coupled receptors to activate platelets. Although aggregation responses to ADP and thromboxane desensitize, there are no reports currently addressing whether activation by one agonist may heterologously desensitize responses to the other. To demonstrate whether responses to ADP or U46619 may be modulated by prior treatment of platelets with the alternate agonist, revealing a level of cross-desensitization between receptor systems. Here we show that pretreatment of platelets with either agonist substantially desensitizes aggregation responses to the other agonist. Calcium responses to thromboxane receptor activation are desensitized by preactivation of P2Y(1) but not P2Y(12) receptors. This heterologous desensitization is mediated by a protein kinase C (PKC)-independent mechanism. Reciprocally, calcium responses to ADP are desensitized by pretreatment of platelets with the thromboxane analogue, U46619, and P2Y(12)-mediated inhibition of adenylate cyclase is also desensitized by pretreatment with U46619. In this direction, desensitization is comprised of two components, a true heterologous component that is PKC-independent, and a homologous component that is mediated through stimulated release of dense granule ADP. This study reveals cross-desensitization between ADP and thromboxane receptor signaling in human platelets. Cross-desensitization is mediated by protein kinases, involving PKC-dependent and independent pathways, and indicates that alterations in the activation state of one receptor may have effects upon the sensitivity of the other receptor system.

Identification of a botulinum C3-like enzyme in bovine brain that catalyzes ADP-ribosylation of GTP-binding proteins.

PubMed

Maehama, T; Takahashi, K; Ohoka, Y; Ohtsuka, T; Ui, M; Katada, T

1991-06-05

A novel enzyme activity was found in bovine brain cytosol that transfers the ADP-ribosyl moiety of NAD to proteins with Mr values of 22,000 and 25,000. The substrates were the same GTP-binding proteins serving as the substrate of an ADP-ribosyltransferase C3 which was produced by a type C strain of Clostridium botulinum. The brain enzyme was partially purified from the cytosol and had a molecular mass of approximately 20,000 on a gel filtration column. The brain endogenous enzyme displayed unique properties similar to those observed with botulinum C3 enzyme. The enzyme activity was markedly stimulated by a protein factor that had been initially found in the cytosol as an activator for botulinum C3-catalyzed ADP-ribosylation (Ohtsuka, T., Nagata, K., Iiri, T., Nozawa, Y., Ueno, K., Ui, M., and Katada, T. (1989) J. Biol. Chem. 264, 15000-15005). The activity of the brain enzyme was also affected by certain types of detergents or phospholipids. The substrate of the brain enzyme was specific for GTP-binding proteins serving as the substrate of botulinum C3 enzyme; the alpha-subunits of trimeric GTP-binding proteins which served as the substrate of cholera or pertussis toxin were not ADP-ribosylated by the endogenous enzyme. Thus, this is the first report showing an endogenous enzyme in mammalian cells that catalyzes ADP-ribosylation of small molecular weight GTP-binding proteins.

Home equity conversion plans as a source of retirement income.

PubMed

Springer, P B

1985-09-01

This article describes in detail a variety of home equity conversion plans and discusses their relevance for social security beneficiaries, as well as for the aged in general. Under these plans, a dormant asset--accumulated home equity--is converted into current retirement income. The plans vary: Some are debt instruments; others involve the sale and leaseback of the residence. Some provide income for a fixed term; others offer a lifetime annuity. Some include a public subsidy; others are free of governmental involvement. The advantages and disadvantages of these plans, as well as examples of how they operate and their respective income potential, are discussed in this article. The relevance of home equity conversion plans for social security beneficiaries is illustrated by means of data from the Retirement History Study. These data allow comparison of various demographic groups in terms of their dependence on social security benefits. Each group is examined in terms of available home equity and home equity potential under several conversion plans.

Preventing infant abductions: an infant security program transitioned into an interdisciplinary model.

PubMed

Hiner, Jacqueline; Pyka, Jeanine; Burks, Colleen; Pisegna, Lily; Gador, Rachel Ann

2012-01-01

Ensuring the safety of infants born in a hospital is a top priority and, therefore, requires a solid infant security plan. Using an interdisciplinary approach and a systematic change process, nursing leadership in collaboration with clinical nurses and security personnel analyzed the infant security program at this community hospital to identify vulnerabilities. By establishing an interdisciplinary approach to infant security, participants were able to unravel a complicated concept, systematically analyze the gaps, and agree to a plan of action. This resulted in improved communication and clarification of roles between the nursing and security divisions. Supply costs decreased by 17.4% after the first year of implementation. Most importantly, this project enhanced and strengthened the existing infant abduction prevention measures, hard wired the importance of infant security, and minimized vulnerabilities.

5 CFR 930.301 - Information systems security awareness training program.

Code of Federal Regulations, 2012 CFR

2012-01-01

... training in system/application life cycle management, risk management, and contingency planning. (4) Chief... security management, system/application life cycle management, risk management, and contingency planning... management; and management and implementation level training in system/application life cycle management...

47 CFR 202.0 - Objectives.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL NATIONAL SECURITY AND... services based on national policy/direction. (4) The capability to execute a telecommunications recovery plan based on national policy/guidance. (c) Notwithstanding any provision regarding NS/EP Planning and...

47 CFR 202.0 - Objectives.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL NATIONAL SECURITY AND... services based on national policy/direction. (4) The capability to execute a telecommunications recovery plan based on national policy/guidance. (c) Notwithstanding any provision regarding NS/EP Planning and...

47 CFR 202.0 - Objectives.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL NATIONAL SECURITY AND... services based on national policy/direction. (4) The capability to execute a telecommunications recovery plan based on national policy/guidance. (c) Notwithstanding any provision regarding NS/EP Planning and...

47 CFR 202.0 - Objectives.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL NATIONAL SECURITY AND... services based on national policy/direction. (4) The capability to execute a telecommunications recovery plan based on national policy/guidance. (c) Notwithstanding any provision regarding NS/EP Planning and...

47 CFR 202.0 - Objectives.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL NATIONAL SECURITY AND... services based on national policy/direction. (4) The capability to execute a telecommunications recovery plan based on national policy/guidance. (c) Notwithstanding any provision regarding NS/EP Planning and...

[Planning a Health Residence for Prison Security Measures, Tuscany (Italy)].

PubMed

Porfido, Eugenio; Colombai, Renato; Scarpa, Franco; Totaro, Michele; Tani, Luca; Baldini, Claudio; Baggiani, Angelo

2016-01-01

Health Residences for Prison Security Measures are facilities hosting psychotic persons who have committed crimes and providing them with personalized rehabilitation and treatment plans to promote their reinstatement in society. The aim of this study was to describe the criteria for planning and designing a prison health residence in the Tuscany region (Italy), to be managed by the regional healthcare service, in line with current regulations, with dedicated staff for providing specific treatment plans and programmes.

Enhancing infrastructure resilience through business continuity planning.

PubMed

Fisher, Ronald; Norman, Michael; Klett, Mary

2017-01-01

Critical infrastructure is crucial to the functionality and wellbeing of the world around us. It is a complex network that works together to create an efficient society. The core components of critical infrastructure are dependent on one another to function at their full potential. Organisations face unprecedented environmental risks such as increased reliance on information technology and telecommunications, increased infrastructure interdependencies and globalisation. Successful organisations should integrate the components of cyber-physical and infrastructure interdependencies into a holistic risk framework. Physical security plans, cyber security plans and business continuity plans can help mitigate environmental risks. Cyber security plans are becoming the most crucial to have, yet are the least commonly found in organisations. As the reliance on cyber continues to grow, it is imperative that organisations update their business continuity and emergency preparedness activities to include this.

75 FR 10507 - Information Security Oversight Office; National Industrial Security Program Policy Advisory...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-08

... NATIONAL ARCHIVES AND RECORDS ADMINISTRATION Information Security Oversight Office; National Industrial Security Program Policy Advisory Committee (NISPPAC) AGENCY: National Archives and Records... individuals planning to attend must be submitted to the Information Security Oversight Office (ISOO) no later...

Information Resource Management Planning in the Office of the Under Secretary of Defense (Acquisition)

DTIC Science & Technology

1989-08-01

Include in this plan the role of the Defense Technical Information Center (DTIC), the Defense Technology Security Administration ( DTSA ), and ODDR&E’s...DTIC = Defense Technical Information Center DTSA = Defense Technology Security Administration DUSD = Deputy Under Secretary of Defense Gloss. 2 DUSD...technologically sensitive requests. The Defense Technology Security Administi ation ( DTSA ) is developing a large system to track foreign military sales

Oligomeric Status and Nucleotide Binding Properties of the Plastid ATP/ADP Transporter 1: Toward a Molecular Understanding of the Transport Mechanism

PubMed Central

Deniaud, Aurélien; Panwar, Pankaj; Frelet-Barrand, Annie; Bernaudat, Florent; Juillan-Binard, Céline; Ebel, Christine; Rolland, Norbert; Pebay-Peyroula, Eva

2012-01-01

Background Chloroplast ATP/ADP transporters are essential to energy homeostasis in plant cells. However, their molecular mechanism remains poorly understood, primarily due to the difficulty of producing and purifying functional recombinant forms of these transporters. Methodology/Principal Findings In this work, we describe an expression and purification protocol providing good yields and efficient solubilization of NTT1 protein from Arabidopsis thaliana. By biochemical and biophysical analyses, we identified the best detergent for solubilization and purification of functional proteins, LAPAO. Purified NTT1 was found to accumulate as two independent pools of well folded, stable monomers and dimers. ATP and ADP binding properties were determined, and Pi, a co-substrate of ADP, was confirmed to be essential for nucleotide steady-state transport. Nucleotide binding studies and analysis of NTT1 mutants lead us to suggest the existence of two distinct and probably inter-dependent binding sites. Finally, fusion and deletion experiments demonstrated that the C-terminus of NTT1 is not essential for multimerization, but probably plays a regulatory role, controlling the nucleotide exchange rate. Conclusions/Significance Taken together, these data provide a comprehensive molecular characterization of a chloroplast ATP/ADP transporter. PMID:22438876

Dynein-ADP as a force-generating intermediate revealed by a rapid reactivation of flagellar axoneme.

PubMed Central

Tani, T; Kamimura, S

1999-01-01

Fragmented flagellar axonemes of sand dollar spermatozoa were reactivated by rapid photolysis of caged ATP. After a time lag of 10 ms, axonemes treated with protease started sliding disintegration. Axonemes without protease digestion started nanometer-scale high-frequency oscillation after a similar time lag. Force development in the sliding disintegration was measured with a flexible glass needle and its time course was corresponded well to that of the dynein-ADP intermediate production estimated using kinetic rates previously reported. However, with a high concentration ( approximately 80 microM) of vanadate, which binds to the dynein-ADP intermediate and forms a stable complex of dynein-ADP-vanadate, the time course of force development in sliding disintegration was not affected at all. In the case of high frequency oscillation, the time lag to start the oscillation, the initial amplitude, and the initial frequency were not affected by vanadate, though the oscillation once started was damped more quickly at higher concentrations of vanadate. These results suggest that during the initial turnover of ATP hydrolysis, force generation of dynein is not blocked by vanadate. A vanadate-insensitive dynein-ADP is postulated as a force-generating intermediate. PMID:10465762

29 CFR 2580.412-1 - Statutory provisions.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., officer and employee of any employee welfare benefit plan or of any employee pension benefit plan subject... Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR TEMPORARY BONDING RULES UNDER THE EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 TEMPORARY BONDING RULES...

49 CFR 172.804 - Relationship to other Federal requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... MATERIALS TABLE, SPECIAL PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY RESPONSE INFORMATION, TRAINING REQUIREMENTS, AND SECURITY PLANS Safety and Security Plans § 172.804 Relationship to other Federal... 49 Transportation 2 2011-10-01 2011-10-01 false Relationship to other Federal requirements. 172...

49 CFR 172.804 - Relationship to other Federal requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... MATERIALS TABLE, SPECIAL PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY RESPONSE INFORMATION, TRAINING REQUIREMENTS, AND SECURITY PLANS Safety and Security Plans § 172.804 Relationship to other Federal... 49 Transportation 2 2014-10-01 2014-10-01 false Relationship to other Federal requirements. 172...

49 CFR 172.804 - Relationship to other Federal requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... MATERIALS TABLE, SPECIAL PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY RESPONSE INFORMATION, TRAINING REQUIREMENTS, AND SECURITY PLANS Safety and Security Plans § 172.804 Relationship to other Federal... 49 Transportation 2 2013-10-01 2013-10-01 false Relationship to other Federal requirements. 172...

49 CFR 172.804 - Relationship to other Federal requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... MATERIALS TABLE, SPECIAL PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY RESPONSE INFORMATION, TRAINING REQUIREMENTS, AND SECURITY PLANS Safety and Security Plans § 172.804 Relationship to other Federal... 49 Transportation 2 2012-10-01 2012-10-01 false Relationship to other Federal requirements. 172...

49 CFR 172.804 - Relationship to other Federal requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... MATERIALS TABLE, SPECIAL PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY RESPONSE INFORMATION, TRAINING REQUIREMENTS, AND SECURITY PLANS Safety and Security Plans § 172.804 Relationship to other Federal... 49 Transportation 2 2010-10-01 2010-10-01 false Relationship to other Federal requirements. 172...

The road to survival goes through PARG.

PubMed

Koh, David W; Dawson, Valina L; Dawson, Ted M

2005-03-01

Unlike poly(ADP-ribose) polymerase-1 (PARP-1), poly(ADP-ribose) glycohydrolase (PARG) has long been a difficult protein to study. However, the complete absence of PARG activity was recently characterized in mice via disruption of the murine PARG gene. As expected, PARG is critical for the maintenance of steady-state poly(ADP-ribose) levels. But surprisingly, the disruption of PARG led to embryonic lethality and increased susceptibility to mild cell stress. Therefore, the protective role of PARG and its involvement in development indicate that these roads to viability go through PARG.

Vincristine impairs platelet aggregation in dogs with lymphoma.

PubMed

Grau-Bassas, E R; Kociba, G J; Couto, C G

2000-01-01

Platelet aggregation before and after administration of 0.5 mg/m2 of vincristine (VCR) was evaluated in 7 dogs with spontaneously occuring lymphoma. Aggregation on platelet-rich plasma separated from blood collected in 3.8% sodium citrate was performed using adenosine diphosphate (ADP), arachidonic acid (AA), and collagen (COL) as agonists. The slope for aggregation in response to ADP was significantly lower after administration of VCR (P = .032). Maximal aggregation after administration of VCR was significantly lower in response to ADP, COL, and AA (P = .03, P = .04, and P = .03, respectively).

Semiconductor radiation detector with internal gain

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

Iwanczyk, Jan; Patt, Bradley E.; Vilkelis, Gintas

An avalanche drift photodetector (ADP) incorporates extremely low capacitance of a silicon drift photodetector (SDP) and internal gain that mitigates the surface leakage current noise of an avalanche photodetector (APD). The ADP can be coupled with scintillators such as CsI(Tl), NaI(Tl), LSO or others to form large volume scintillation type gamma ray detectors for gamma ray spectroscopy, photon counting, gamma ray counting, etc. Arrays of the ADPs can be used to replace the photomultiplier tubes (PMTs) used in conjunction with scintillation crystals in conventional gamma cameras for nuclear medical imaging.

6 CFR 27.210 - Submissions schedule.

Code of Federal Regulations, 2010 CFR

2010-01-01

... in any subsequent Federal Register notice. (2) Security Vulnerability Assessment. Unless otherwise notified, a covered facility must complete and submit a Security Vulnerability Assessment within 90... Department's approval of the facility's Site Security Plan. (2) Security Vulnerability Assessment. Unless...

Comparative Mg(2+)-dependent sequential covalent binding stoichiometries of 3'-O-(4-benzoyl)benzoyl adenosine 5'-diphosphate of MF1, TF1, and the alpha 3 beta 3 core complex of TF1. The binding change motif is independent of the F1 gamma delta epsilon subunits.

PubMed

Aloise, P; Kagawa, Y; Coleman, P S

1991-06-05

Three F1 preparations, the beef heart (MF1) and thermophilic bacterium (TF1) holoenzymes, and the alpha 3 beta 3 "core" complex of TF1 reconstituted from individually expressed alpha and beta subunits, were compared as to their kinetic and binding stoichiometric responses to covalent photoaffinity labeling with BzATP and BzADP (+/- Mg2+). Each enzyme displayed an enhanced pseudo-first order rate of photoinhibition and one-third of the sites covalent binding to a catalytic site for full inhibition, plus, but not minus Mg2+. Titration of near stoichiometric [MgBzADP]/[F1] ratios during photolysis disclosed two sequential covalent binding patterns for each enzyme; a high affinity binding corresponding to unistoichiometric covalent association concomitant with enzyme inhibition, followed by a low affinity multisite-saturating covalent association. Thus, in the absence of the structural asymmetry inducing gamma delta epsilon subunits of the holoenzyme, the sequential binding of nucleotide at putative catalytic sites on the alpha 3 beta 3 complex of any F1 appears sufficient to effect binding affinity changes. With MF1, final covalent saturation of BzADP-accessible sites was achieved with 2 mol of BzADP/mol of enzyme, but with TF1 or its alpha 3 beta 3 complex, saturation required 3 mol of BzADP/mol of enzyme. Such differential final labeling stoichiometries could arise because of the endogenous presence of 1 nucleotide already bound to one of the 3 potential catalytic sites on normally prepared MF1, whereas TF1, possessing no endogenous nucleotide, has 3 vacant BzADP-accessible sites. Kinetics measurements revealed that regardless of the incremental extent of inhibition of the TF1 holoenzyme by BzADP during photolysis, the two higher apparent Km values (approximately 1.5 x 10(-4) and approximately 10(-3) M, respectively) of the progressively inactivated incubation are unchanged relative to fully unmodified enzyme. As reported for BzATP (or BzADP) and MF1 (Ackerman, S.H., Grubmeyer, C., and Coleman, P.S. (1987) J. Biol. Chem. 262, 13765-13772), this supports the fact that the photocovalent inhibition of F1 is a one-hit one-kill phenomenon. Isoelectric focusing gels revealed that [3H]BzADP covalently modifies both TF1 and MF1 exclusively on the beta subunit, whether or not Mg2+ is present. A single 19-residue [3H]BzADP-labeled peptide was resolved from a tryptic digest of MF1, and this peptide corresponded with the one believed to contain at least a portion of the beta subunit catalytic site domain (i.e. beta Ala-338----beta Arg-356).

Advanced Drying Process for Lower Manufacturing Cost of Electrodes

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

Ahmad, Iftikhar; Zhang, Pu

For this Vehicle Technologies Incubator/Energy Storage R&D topic, Lambda Technologies teamed with Navitas Systems and proposed a new advanced drying process that promised a 5X reduction in electrode drying time and significant reduction in the cost of large format lithium batteries used in PEV's. The operating principle of the proposed process was to use penetrating radiant energy source Variable Frequency Microwaves (VFM), that are selectively absorbed by the polar water or solvent molecules instantly in the entire volume of the electrode. The solvent molecules are thus driven out of the electrode thickness making the process more efficient and much fastermore » than convective drying method. To evaluate the Advanced Drying Process (ADP) a hybrid prototype system utilizing VFM and hot air flow was designed and fabricated. While VFM drives the solvent out of the electrode thickness, the hot air flow exhausts the solvent vapors out of the chamber. The drying results from this prototype were very encouraging. For water based anodes there is a 5X drying advantage (time & length of oven) in using ADP over standard drying system and for the NMP based cathodes the reduction in drying time has 3X benefit. For energy savings the power consumption measurements were performed to ADP prototype and compared with the convection standard drying oven. The data collected demonstrated over 40% saving in power consumption with ADP as compared to the convection drying systems. The energy savings are one of the operational cost benefits possible with ADP. To further speed up the drying process, the ADP prototype was explored as a booster module before the convection oven and for the electrode material being evaluated it was possible to increase the drying speed by a factor of 4, which could not be accomplished with the standard dryer without surface defects and cracks. The instantaneous penetration of microwave in the entire slurry thickness showed a major advantage in rapid drying of the electrode materials. For the existing electrode materials, the material analysis and cell characterization data from ADP dried electrodes showed equivalent (or slightly better) performance. However, for high loading and thicker electrode materials (for high energy densities) the ADP advantages are more prominent. There was less binder migration, the resistance was lower hence the current capacities and retention of the battery cells were higher. The success of the project has enabled credible communications with commercial end users as well as battery coating line integrators. Goal is to scale ADP up for high volume manufacturing of Li-ion battery electrodes. The implementation of ADP in high volume manufacturing will reduce a high cost production step to bring the overall price of Li-ion batteries down. This will ultimately have a positive impact on the public by making electric and hybrid vehicles more affordable.« less

Pertussis toxin-catalyzed ADP-ribosylation of a G protein in mouse oocytes, eggs, and preimplantation embryos: Developmental changes and possible functional roles

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

Jones, J.; Schultz, R.M.

1990-06-01

G proteins, which in many somatic cells serve as mediators of signal transduction, were identified in preimplantation mouse embryos by their capacity to undergo pertussis toxin-catalyzed ADP-ribosylation. Two pertussis toxin (PT) substrates with Mr = 38,000 and 39,000 (alpha 38 and alpha 39) are present in approximately equal amounts. Relative to the amount in freshly isolated germinal vesicle (GV)-intact oocytes, the amount of PT-catalyzed ADP-ribosylation of alpha 38-39 falls during oocyte maturation, rises between the one- and two-cell stages, falls by the eight-cell and morula stages, and increases again by the blastocyst stage. The decrease in PT-catalyzed ADP-ribosylation of alphamore » 38-39 that occurs during oocyte maturation, however, does not require germinal vesicle breakdown (GVBD), since inhibiting GVBD with 3-isobutyl-1-methyl xanthine (IBMX) does not prevent the decrease in the extent of PT-catalyzed ADP-ribosylation. A biologically active phorbol diester (12-O-tetradecanoyl phorbol 13-acetate), but not an inactive one (4 alpha-phorbol 12,13-didecanoate, 4 alpha-PDD), totally inhibits the increase in PT-catalyzed ADP-ribosylation of alpha 38-39 that occurs between the one- and two-cell stage; TPA inhibits cleavage, but not transcriptional activation, which occurs in the two-cell embryo. In contrast, cytochalasin D, genistein, or aphidicolin, each of which inhibits cleavage of one-cell embryos, or alpha-amanitin or H8, each of which inhibits transcriptional activation but not cleavage of one-cell embryos, have little or inhibitory effects on the increase in PT-catalyzed ADP-ribosylation of alpha 38-39. Results of immunoblotting experiments using an antibody that is highly specific for alpha il-3 reveal the presence of a cross-reactive species of Mr = 38,000 (alpha 38) in the GV-intact oocyte, metaphase II-arrested egg, and one-, two-cell embryos.« less

Probing the accuracy and precision of Hirshfeld atom refinement with HARt interfaced with Olex2.

PubMed

Fugel, Malte; Jayatilaka, Dylan; Hupf, Emanuel; Overgaard, Jacob; Hathwar, Venkatesha R; Macchi, Piero; Turner, Michael J; Howard, Judith A K; Dolomanov, Oleg V; Puschmann, Horst; Iversen, Bo B; Bürgi, Hans-Beat; Grabowsky, Simon

2018-01-01

Hirshfeld atom refinement (HAR) is a novel X-ray structure refinement technique that employs aspherical atomic scattering factors obtained from stockholder partitioning of a theoretically determined tailor-made static electron density. HAR overcomes many of the known limitations of independent atom modelling (IAM), such as too short element-hydrogen distances, r ( X -H), or too large atomic displacement parameters (ADPs). This study probes the accuracy and precision of anisotropic hydrogen and non-hydrogen ADPs and of r ( X -H) values obtained from HAR. These quantities are compared and found to agree with those obtained from (i) accurate neutron diffraction data measured at the same temperatures as the X-ray data and (ii) multipole modelling (MM), an established alternative method for interpreting X-ray diffraction data with the help of aspherical atomic scattering factors. Results are presented for three chemically different systems: the aromatic hydro-carbon rubrene (orthorhombic 5,6,11,12-tetra-phenyl-tetracene), a co-crystal of zwitterionic betaine, imidazolium cations and picrate anions (BIPa), and the salt potassium hydrogen oxalate (KHOx). The non-hydrogen HAR-ADPs are as accurate and precise as the MM-ADPs. Both show excellent agreement with the neutron-based values and are superior to IAM-ADPs. The anisotropic hydrogen HAR-ADPs show a somewhat larger deviation from neutron-based values than the hydrogen SHADE-ADPs used in MM. Element-hydrogen bond lengths from HAR are in excellent agreement with those obtained from neutron diffraction experiments, although they are somewhat less precise. The residual density contour maps after HAR show fewer features than those after MM. Calculating the static electron density with the def2-TZVP basis set instead of the simpler def2-SVP one does not improve the refinement results significantly. All HARs were performed within the recently introduced HARt option implemented in the Olex2 program. They are easily launched inside its graphical user interface following a conventional IAM.

Improved therapeutic effectiveness by combining recombinant p14(ARF) with antisense complementary DNA of EGFR in laryngeal squamous cell carcinoma.

PubMed

Liu, Feng; Du, JinTao; Xian, Junming; Liu, Yafeng; Liu, Shixi; Lin, Yan

2015-01-01

The tumor suppressor p14(ARF) and proto-oncogene epidermal growth factor receptor (EGFR) play important roles in the development of laryngeal squamous cell carcinoma (LSCC). This study was aimed to determine whether combining recombinant p14(ARF) with antisense complementary DNA of EGFR could improve the therapeutic effectiveness in LSCC. After human larynx cancer cells (Hep-2) were infected with recombinant adenoviruses (Ad-p14(ARF) and Ad-antisense EGFR) together or alone in vitro, the proliferation and cell cycle distribution of Hep-2 cells were detected by MTT assay and flow cytometer analysis, respectively. Furthermore, the antitumor effects of recombinant adenoviruses together or alone on Hep-2 xenografts were examined in vivo. The levels of p14(ARF) and EGFR expressed in Hep-2 cells and xenografts were determined by western blot assay. Ad-p14(ARF) combining with Ad-antisense EGFR markedly inhibited the Hep-2 proliferation compared with alone (P=0.001, P=0.002 respectively). Combination of Ad-p14(ARF) and Ad-antisense EGFR led to the proportion of Hep-2 cells in G0/G1 phases increased by up to 86.9%. The down-expression of EGFR protein and overexpression of p14(ARF) protein were observed in vitro and in vivo, and this effect was preserved when Ad-p14(ARF) was combined with Ad-antisense EGFR. Besides, Ad-p14(ARF) plus Ad-antisense EGFR significantly (P<0.05) increased the antitumor activity against Hep-2 tumor xenografts comparing with Ad-p14(ARF) or Ad-antisense EGFR alone. Combination Ad-p14(ARF) with Ad-antisense EGFR significantly increased the antitumor responses in LSCC. An effectively potential gene therapy to prevent proliferation of LSCC was provided. Copyright © 2015 Elsevier Inc. All rights reserved.

Probing the accuracy and precision of Hirshfeld atom refinement with HARt interfaced with Olex2

PubMed Central

Fugel, Malte; Hathwar, Venkatesha R.; Turner, Michael J.; Howard, Judith A. K.

2018-01-01

Hirshfeld atom refinement (HAR) is a novel X-ray structure refinement technique that employs aspherical atomic scattering factors obtained from stockholder partitioning of a theoretically determined tailor-made static electron density. HAR overcomes many of the known limitations of independent atom modelling (IAM), such as too short element–hydrogen distances, r(X—H), or too large atomic displacement parameters (ADPs). This study probes the accuracy and precision of anisotropic hydrogen and non-hydrogen ADPs and of r(X—H) values obtained from HAR. These quantities are compared and found to agree with those obtained from (i) accurate neutron diffraction data measured at the same temperatures as the X-ray data and (ii) multipole modelling (MM), an established alternative method for interpreting X-ray diffraction data with the help of aspherical atomic scattering factors. Results are presented for three chemically different systems: the aromatic hydro­carbon rubrene (orthorhombic 5,6,11,12-tetra­phenyl­tetracene), a co-crystal of zwitterionic betaine, imidazolium cations and picrate anions (BIPa), and the salt potassium hydrogen oxalate (KHOx). The non-hydrogen HAR-ADPs are as accurate and precise as the MM-ADPs. Both show excellent agreement with the neutron-based values and are superior to IAM-ADPs. The anisotropic hydrogen HAR-ADPs show a somewhat larger deviation from neutron-based values than the hydrogen SHADE-ADPs used in MM. Element–hydrogen bond lengths from HAR are in excellent agreement with those obtained from neutron diffraction experiments, although they are somewhat less precise. The residual density contour maps after HAR show fewer features than those after MM. Calculating the static electron density with the def2-TZVP basis set instead of the simpler def2-SVP one does not improve the refinement results significantly. All HARs were performed within the recently introduced HARt option implemented in the Olex2 program. They are easily launched inside its graphical user interface following a conventional IAM. PMID:29354269

Estimating body fat in NCAA Division I female athletes: a five-compartment model validation of laboratory methods.

PubMed

Moon, Jordan R; Eckerson, Joan M; Tobkin, Sarah E; Smith, Abbie E; Lockwood, Christopher M; Walter, Ashley A; Cramer, Joel T; Beck, Travis W; Stout, Jeffrey R

2009-01-01

The purpose of the present study was to determine the validity of various laboratory methods for estimating percent body fat (%fat) in NCAA Division I college female athletes (n = 29; 20 +/- 1 year). Body composition was assessed via hydrostatic weighing (HW), air displacement plethysmography (ADP), and dual-energy X-ray absorptiometry (DXA), and estimates of %fat derived using 4-compartment (C), 3C, and 2C models were compared to a criterion 5C model that included bone mineral content, body volume (BV), total body water, and soft tissue mineral. The Wang-4C and the Siri-3C models produced nearly identical values compared to the 5C model (r > 0.99, total error (TE) < 0.40%fat). For the remaining laboratory methods, constant error values (CE) ranged from -0.04%fat (HW-Siri) to -3.71%fat (DXA); r values ranged from 0.89 (ADP-Siri, ADP-Brozek) to 0.93 (DXA); standard error of estimate values ranged from 1.78%fat (DXA) to 2.19%fat (ADP-Siri, ADP-Brozek); and TE values ranged from 2.22%fat (HW-Brozek) to 4.90%fat (DXA). The limits of agreement for DXA (-10.10 to 2.68%fat) were the largest with a significant trend of -0.43 (P < 0.05). With the exception of DXA, all of the equations resulted in acceptable TE values (<3.08%fat). However, the results for individual estimates of %fat using the Brozek equation indicated that the 2C models that derived BV from ADP and HW overestimated (5.38, 3.65%) and underestimated (5.19, 4.88%) %fat, respectively. The acceptable TE values for both HW and ADP suggest that these methods are valid for estimating %fat in college female athletes; however, the Wang-4C and Siri-3C models should be used to identify individual estimates of %fat in this population.

Evaluation of the BOD POD and leg-to-leg bioelectrical impedance analysis for estimating percent body fat in National Collegiate Athletic Association Division III collegiate wrestlers.

PubMed

Dixon, Curt B; Deitrick, Ronald W; Pierce, Joseph R; Cutrufello, Paul T; Drapeau, Linda L

2005-02-01

The purpose of this study was to compare percent body fat (%BF) estimated by air displacement plethysmography (ADP) and leg-to-leg bioelectrical impedance analysis (LBIA) with hydrostatic weighing (HW) in a group (n = 25) of NCAA Division III collegiate wrestlers. Body composition was assessed during the preseason wrestling weight certification program (WCP) using the NCAA approved methods (HW, 3-site skinfold [SF], and ADP) and LBIA, which is currently an unaccepted method of assessment. A urine specific gravity less than 1.020, measured by refractometry, was required before all testing. Each subject had all of the assessments performed on the same day. LBIA measurements (Athletic mode) were determined using a Tanita body fat analyzer (model TBF-300A). Hydrostatic weighing, corrected for residual lung volume, was used as the criterion measurement. The %BF data (mean +/- SD) were LBIA (12.3 +/- 4.6), ADP (13.8 +/- 6.3), SF (14.2 +/- 5.3), and HW (14.5 +/- 6.0). %BF estimated by LBIA was significantly (p < 0.01) smaller than HW and SF. There were no significant differences in body density or %BF estimated by ADP, SF, and HW. All methods showed significant correlations (r = 0.80-0.96; p < 0.01) with HW. The standard errors of estimate (SEE) for %BF were 1.68, 1.87, and 3.60%; pure errors (PE) were 1.88, 1.94, and 4.16% (ADP, SF, and LBIA, respectively). Bland-Atman plots for %BF demonstrated no systematic bias for ADP, SF, and LBIA when compared with HW. These preliminary findings support the use of ADP and SF for estimating %BF during the NCAA WCP in Division III wrestlers. LBIA, which consistently underestimated %BF, is not supported by these data as a valid assessment method for this athletic group.

Platelet Activation and Clopidogrel Effects on ADP-Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3.

PubMed

Li, R H L; Stern, J A; Ho, V; Tablin, F; Harris, S P

2016-09-01

Clopidogrel is commonly prescribed to cats with perceived increased risk of thromboembolic events, but little information exists regarding its antiplatelet effects. To determine effects of clopidogrel on platelet responsiveness in cats with or without the A31P mutation in the MYBPC3 gene. A secondary aim was to characterize variability in feline platelet responses to clopidogrel. Fourteen healthy cats from a Maine Coon/outbred mixed Domestic cat colony: 8 cats homozygous for A31P mutation in the MYPBC3 gene and 6 wild-type cats without the A31P mutation. Ex vivo study. All cats received clopidogrel (18.75 mg PO q24h) for 14 days. Before and after clopidogrel treatment, adenosine diphosphate (ADP)-induced P-selectin expression was evaluated. ADP- and thrombin-induced platelet aggregation was measured by optical aggregometry (OA). Platelet pVASP and ADP receptor response index (ARRI) were measured by Western blot analysis. Platelet activation from cats with the A31P mutation was significantly (P = .0095) increased [35.55% (18.58-48.55) to 58.90% (24.85-69.90)], in response to ADP. Clopidogrel treatment attenuated ADP-induced P-selectin expression and platelet aggregation. ADP- and PGE 1 -treated platelets had a similar level of pVASP as PGE 1 -treated platelets after clopidogrel treatment. Clopidogrel administration resulted in significantly lower ARRI [24.13% (12.46-35.50) to 11.30% (-7.383 to 23.27)] (P = .017). Two of 13 cats were nonresponders based on OA and flow cytometry. Clopidogrel is effective at attenuating platelet activation and aggregation in some cats. Cats with A31P mutation had increased platelet activation relative to the variable response seen in wild-type cats. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Officer Computer Utilization Report

DTIC Science & Technology

1992-03-01

Shipboard Non-tactical ADP Program (SNAP),Navy Intelligence Processing System (NIPS), Retail Operation Management (ROM)). Mainframe - An extremely...ADP Program (SNAP), Navy Intelligence Processing System (NIPS), Retail Operation Management (ROM), etc.) @0230@6 7 7. Technical/tactical systems (e.g

Design, Synthesis, and Chemical and Biological Properties of Cyclic ADP-4-Thioribose as a Stable Equivalent of Cyclic ADP-Ribose.

PubMed

Tsuzuki, Takayoshi; Takano, Satoshi; Sakaguchi, Natsumi; Kudoh, Takashi; Murayama, Takashi; Sakurai, Takashi; Hashii, Minako; Higashida, Haruhiro; Weber, Karin; Guse, Andreas H; Kameda, Tomoshi; Hirokawa, Takatsugu; Kumaki, Yasuhiro; Arisawa, Mitsuhiro; Potter, Barry V L; Shuto, Satoshi

2014-01-01

Here we describe the successful synthesis of cyclic ADP-4-thioribose (cADPtR, 3 ), designed as a stable mimic of cyclic ADP-ribose (cADPR, 1 ), a Ca 2+ -mobilizing second messenger, in which the key N1-β-thioribosyladenosine structure was stereoselectively constructed by condensation between the imidazole nucleoside derivative 8 and the 4-thioribosylamine 7 via equilibrium in 7 between the α-anomer ( 7α ) and the β-anomer ( 7β ) during the reaction course. cADPtR is, unlike cADPR, chemically and biologically stable, while it effectively mobilizes intracellular Ca 2+ like cADPR in various biological systems, such as sea urchin homogenate, NG108-15 neuronal cells, and Jurkat T-lymphocytes. Thus, cADPtR is a stable equivalent of cADPR, which can be useful as a biological tool for investigating cADPR-mediated Ca 2+ -mobilizing pathways.

Clostridium spiroforme toxin is a binary toxin which ADP-ribosylates cellular actin.

PubMed

Popoff, M R; Boquet, P

1988-05-16

We have purified from Clostridium spiroforme strain 246 an heterogeneous population of proteins (Sa) ranging from 43 to 47 kilodaltons exhibiting ADP-ribosyl transferase activity as do C. botulinum C2 toxin component I or the ia chain of C. perfringens E iota toxin. C. spiriforme Sa had alone no activity upon injection in mice or inoculated to Vero cells. When spiroforme ADP ribosyl transferase were mixed with a trypsin activated protein (Sb) separated from C. spiroforme bacterial supernatant, a lethal effect in mice and cytotoxicity on Vero cells were recorded. The Sa cross-reacted immunologically with either the light chain of C. perfringens E iota toxin or the ADP-ribosyl transferase from C. difficile 196 strain. No immunological relatedness was observed between Sa and C2 toxin component I. C. spiroforme toxin is thus another binary toxin close to iota.

National Research and Development Plan for Aviation Safety, Security, Efficiency and Environmental Compatibility.

DOT National Transportation Integrated Search

1999-11-01

This plan describes coordinated long-term research initiatives to bring about advances in aviation that will be required in the opening decades of the next century. The White House Commission on Aviation Safety and Security and the National Civil Avi...

National Research and Development Plan For Aviation Safety, Security, Efficiency, and Environmental Compatibility

DOT National Transportation Integrated Search

1999-11-01

This plan describes coordinated long-term research initiatives to bring about advances in aviation that will be required in the opening decades of the next century. The White House Commission on Aviation Safety and Security and the National Civil Avi...

75 FR 2161 - Proposed Extension of Information Collection; Comment Request; Employee Benefit Plan Claims...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-14

... DEPARTMENT OF LABOR Employee Benefits Security Administration Proposed Extension of Information Collection; Comment Request; Employee Benefit Plan Claims Procedures Under ERISA AGENCY: Employee Benefits... Employee Benefits Security Administration (EBSA) is soliciting comments on a proposed extension of the...

75 FR 38595 - Guidance to States Regarding Driver History Record Information Security, Continuity of Operation...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-02

... Standards and Technology's (NIST) Computer Security Division maintains a Computer Security Resource Center... Regarding Driver History Record Information Security, Continuity of Operation Planning, and Disaster... (SDLAs) to support their efforts at maintaining the security of information contained in the driver...

Examining Long Term Climate Related Security Risks through the Use of Gaming and Scenario Planning

DTIC Science & Technology

2016-10-24

114 Examining Long-Term Climate-Related Security Risks through the Use of Gaming and Scenario Planning Catherine M. Schkoda, Shawna G. Cuan, and...E. D. McGrady Abstract: This paper examines four possible climate change-related security risks that emerged from an international game and scenario...potential for an emerging disparity between regions over the consensus and control of climate change-related technologies. Keywords: gaming , scenario

Defense Technology Security Administration Strategic Plan 2009-2010

DTIC Science & Technology

2008-12-22

NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Defense Technology Security Administration ( DTSA ),Washington,DC 8. PERFORMING ORGANIZATION...Security Administration This document is unclassifi ed in its entirety. Photography courtesy of Defense Link and DTSA . Document printed 2009. DTSA ...STRATEGIC PLAN 2009-2010 C O N T E N T S Message from the Director 2 Envisioning 2010 3 Our Way Ahead 5 We Are DTSA 18 Metrics Matrix 24 DTSA

Contracting-out in the United Kingdom: a partnership between social security and private pension plans.

PubMed

Daykin, Chris

2002-01-01

Contracting-out was introduced in the United Kingdom in 1978 as part of the arrangements for the State Earnings-Related Pension Scheme (SERPS) in order to avoid duplication with the existing well-developed defined benefit occupational pension plan sector. Members and sponsors of contracted-out schemes were able to save on their social security contributions in recognition of the fact that they were accruing equivalent benefits through an occupational pension plan. Later on this concept was extended to those with individual money purchase pension plans. This article considers a brief history of contracting-out, the principles of contracting-out, some problems associated with contracting-out, the implications of the introduction of stakeholder pensions and State Second Pension, and the latest rebate review and rebate orders. It examines how U.K. pensions policy since 1978 has been based on a partnership between social security and private pension plans.

Stereochemical control over Mn(II)-Thio versus Mn(II)-Oxy coordination in adenosine 5 prime -O-(1-thiodiphosphate) complexes at the active site of creatine kinase

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

Smithers, G.W.; Sammons, R.D.; Goodhart, P.J.

1989-02-21

The stereochemical configurations of the Mn(II) complexes with the resolved epimers of adenosine 5{prime}-O-(1-thiodiphosphate) (ADP{alpha}S), bound at the active site of creatine kinase, have been determined in order to assess the relative strengths of enzymic stereoselectivity versus Lewis acid/base preferences in metal-ligand binding. Electron paramagnetic resonance (EPR) data have been obtained for Mn(II) in anion-stabilized, dead-end (transition-state analogue) complexes, in ternary enzyme-Mn{sup II}ADP{alpha}S complexes, and in the central complexes of the equilibrium mixture. The modes of coordination of Mn(II) at P{sub alpha} in the nitrate-stabilized, dead-end complexes with each epimer of ADP{alpha}S were ascertained by EPR measurements with (R{sub p})-({alpha}-{supmore » 17}O)ADP{alpha}S and (S{sub p})-({alpha}-{sup 17}O)ADP{alpha}S. A reduction in the magnitude of the {sup 55}Mn hyperfine coupling constant in the spectrum for the complex containing (S{sub p})-ADP{alpha}S is indicative of Mn(II)-thio coordination at P{sub alpha}. The results indicate that a strict discrimination for a unique configuration of the metal-nucleotide substrate is expressed upon binding of all of the substrates to form the active complex (or an analogue thereof). This enzymic stereoselectivity provides sufficient binding energy to overcome an intrinsic preference for the hard Lewis acid Mn(II) to coordinate to the hard Lewis base oxygen.« less

Probing the nucleotide binding domain of the osmoregulator EnvZ using fluorescent nucleotide derivatives.

PubMed

Plesniak, Leigh; Horiuchi, Yuki; Sem, Daniel; Meinenger, David; Stiles, Linda; Shaffer, Jennifer; Jennings, Patricia A; Adams, Joseph A

2002-11-26

EnvZ is a histidine protein kinase important for osmoregulation in bacteria. While structural data are available for this enzyme, the nucleotide binding pocket is not well characterized. The ATP binding domain (EnvZB) was expressed, and its ability to bind nucleotide derivatives was assessed using equilbrium and stopped-flow fluorescence spectroscopy. The fluorescence emission of the trinitrophenyl derivatives, TNP-ATP and TNP-ADP, increase upon binding to EnvZB. The fluorescence enhancements were quantitatively abolished in the presence of excess ADP, indicating that the fluorescent probes occupy the nucleotide binding pocket. Both TNP-ATP and TNP-ADP bind to EnvZB with high affinity (K(d) = 2-3 microM). The TNP moiety attached to the ribose ring does not impede access of the fluorescent nucleotide into the binding pocket. The association rate constant for TNP-ADP is 7 microM(-1) s(-1), a value consistent with those for natural nucleotides and the eucaryotic protein kinases. Using competition experiments, it was found that ATP and ADP bind 30- and 150-fold more poorly, respectively, than the corresponding TNP-derivatized forms. Surprisingly, the physiological metal Mg(2+) is not required for ADP binding and only enhances ATP affinity by 3-fold. Although portions of the nucleotide pocket are disordered, the recombinant enzyme is highly stable, unfolding only at temperatures in excess of 70 degrees C. The unusually high affinity of the TNP derivatives compared to the natural nucleotides suggests that hydrophobic substitutions on the ribose ring enforce an altered binding mode that may be exploited for drug design strategies.

ADP binding to TF1 and its subunits induces ultraviolet spectral changes.

PubMed

Hisabori, T; Yoshida, M; Sakurai, H

1986-09-01

Adenine nucleotide binding sites on the coupling factor ATPase of thermophilic bacterium PS3 (TF1) were investigated by UV spectroscopy and by equilibrium dialysis. When ADP was mixed with TF1 in the presence and in the absence of Mg2+, an UV absorbance change was induced (t1/2 approximately 1 min) with a peak at about 278 nm and a trough at about 250 nm. Similar spectral changes were induced by ADP with the isolated beta subunits in the presence and in the absence of Mg2+, and with the isolated alpha subunits in the presence of Mg2+ although the magnitudes of the changes were different. From equilibrium dialysis measurement we identified two classes of nucleotide binding sites in TF1 in the presence of Mg2+, three high-affinity sites (Kd = 61 nM) and three low-affinity sites (Kd = 87 microM). In the absence of Mg2+, TF1 has one high-affinity site (Kd less than 10 nM) and five low-affinity sites (Kd = 100 microM). Moreover, we found a single Mg2+-dependent ADP binding site on the isolated alpha subunit and a single Mg2+-independent ADP binding site on the isolated beta subunit. From the above observations, we concluded that the three Mg2+-dependent high-affinity sites for ADP are located on the alpha subunit in TF1 and that the single high-affinity site is located on one of the beta subunits in TF1 in the absence of Mg2+.

Water-mediated protein-fluorophore interactions modulate the affinity of an ABC-ATPase/TNP-ADP complex.

PubMed

Oswald, Christine; Jenewein, Stefan; Smits, Sander H J; Holland, I Barry; Schmitt, Lutz

2008-04-01

TNP-modified nucleotides have been used extensively to study protein-nucleotide interactions. In the case of ABC-ATPases, application of these powerful tools has been greatly restricted due to the significantly higher affinity of the TNP-nucleotide for the corresponding ABC-ATPase in comparison to the non-modified nucleotides. To understand the molecular changes occurring upon binding of the TNP-nucleotide to an ABC-ATPase, we have determined the crystal structure of the TNP-ADP/HlyB-NBD complex at 1.6A resolution. Despite the higher affinity of TNP-ADP, no direct fluorophore-protein interactions were observed. Unexpectedly, only water-mediated interactions were detected between the TNP moiety and Tyr(477), that is engaged in pi-pi stacking with the adenine ring, as well as with two serine residues (Ser(504) and Ser(509)) of the Walker A motif. Interestingly, the side chains of these two serine residues adopt novel conformations that are not observed in the corresponding ADP structure. However, in the crystal structure of the S504A mutant, which binds TNP-ADP with similar affinity to the wild type enzyme, a novel TNP-water interaction compensates for the missing serine side chain. Since this water molecule is not present in the wild type enzyme, these results suggest that only water-mediated interactions provide a structural explanation for the increased affinity of TNP-nucleotides towards ABC-ATPases. However, our results also imply that in silico approaches such as docking or modeling cannot directly be applied to generate 'affinity-adopted' ADP- or ATP-analogs for ABC-ATPases.

Novel essential residues of Hda for interaction with DnaA in the regulatory inactivation of DnaA: unique roles for Hda AAA Box VI and VII motifs.

PubMed

Nakamura, Kenta; Katayama, Tsutomu

2010-04-01

Escherichia coli ATP-DnaA initiates chromosomal replication. For preventing extra-initiations, a complex of ADP-Hda and the DNA-loaded replicase clamp promotes DnaA-ATP hydrolysis, yielding inactive ADP-DnaA. However, the Hda-DnaA interaction mode remains unclear except that the Hda Box VII Arg finger (Arg-153) and DnaA sensor II Arg-334 within each AAA(+) domain are crucial for the DnaA-ATP hydrolysis. Here, we demonstrate that direct and functional interaction of ADP-Hda with DnaA requires the Hda residues Ser-152, Phe-118 and Asn-122 as well as Hda Arg-153 and DnaA Arg-334. Structural analyses suggest intermolecular interactions between Hda Ser-152 and DnaA Arg-334 and between Hda Phe-118 and the DnaA Walker B motif region, in addition to an intramolecular interaction between Hda Asn-122 and Arg-153. These interactions likely sustain a specific association of ADP-Hda and DnaA, promoting DnaA-ATP hydrolysis. Consistently, ATP-DnaA and ADP-DnaA interact with the ADP-Hda-DNA-clamp complex with similar affinities. Hda Phe-118 and Asn-122 are contained in the Box VI region, and their hydrophobic and electrostatic features are basically conserved in the corresponding residues of other AAA(+) proteins, suggesting a conserved role for Box VI. These findings indicate novel interaction mechanisms for Hda-DnaA as well as a potentially fundamental mechanism in AAA(+) protein interactions.

Twenty-Five Year Site Plan FY2013 - FY2037

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

Jones, William H.

2012-07-12

Los Alamos National Laboratory (the Laboratory) is the nation's premier national security science laboratory. Its mission is to develop and apply science and technology to ensure the safety, security, and reliability of the United States (U.S.) nuclear stockpile; reduce the threat of weapons of mass destruction, proliferation, and terrorism; and solve national problems in defense, energy, and the environment. The fiscal year (FY) 2013-2037 Twenty-Five Year Site Plan (TYSP) is a vital component for planning to meet the National Nuclear Security Administration (NNSA) commitment to ensure the U.S. has a safe, secure, and reliable nuclear deterrent. The Laboratory also usesmore » the TYSP as an integrated planning tool to guide development of an efficient and responsive infrastructure that effectively supports the Laboratory's missions and workforce. Emphasizing the Laboratory's core capabilities, this TYSP reflects the Laboratory's role as a prominent contributor to NNSA missions through its programs and campaigns. The Laboratory is aligned with Nuclear Security Enterprise (NSE) modernization activities outlined in the NNSA Strategic Plan (May 2011) which include: (1) ensuring laboratory plutonium space effectively supports pit manufacturing and enterprise-wide special nuclear materials consolidation; (2) constructing the Chemistry and Metallurgy Research Replacement Nuclear Facility (CMRR-NF); (3) establishing shared user facilities to more cost effectively manage high-value, experimental, computational and production capabilities; and (4) modernizing enduring facilities while reducing the excess facility footprint. Th is TYSP is viewed by the Laboratory as a vital planning tool to develop an effi cient and responsive infrastructure. Long range facility and infrastructure development planning are critical to assure sustainment and modernization. Out-year re-investment is essential for sustaining existing facilities, and will be re-evaluated on an annual basis. At the same time, major modernization projects will require new line-item funding. This document is, in essence, a roadmap that defines a path forward for the Laboratory to modernize, streamline, consolidate, and sustain its infrastructure to meet its national security mission.« less

Administrative automation in a scientific environment

NASA Technical Reports Server (NTRS)

Jarrett, J. R.

1984-01-01

Although the scientific personnel at GSFC were advanced in the development and use of hardware and software for scientific applications, resistance to the use of automation or purchase of terminals, software and services, specifically for administrative functions was widespread. The approach used to address problems and constraints and plans for administrative automation within the Space and Earth Sciences Directorate are delineated. Accomplishments thus far include reduction of paperwork and manual efforts; improved communications through telemail and committees; additional support staff; increased awareness at all levels on ergonomic concerns and the need for training; better equipment; improved ADP skills through experience; management commitment; and an overall strategy for automating.

Security breaches: tips for assessing and limiting your risks.

PubMed

Coons, Leeanne R

2011-01-01

As part of their compliance planning, medical practices should undergo a risk assessment to determine any vulnerability within the practice relative to security breaches. Practices should also implement safeguards to limit their risks. Such safeguards include facility access controls, information and electronic media management, use of business associate agreements, and education and enforcement. Implementation of specific policies and procedures to address security incidents is another critical step that medical practices should take as part of their security incident prevention plan. Medical practices should not only develop policies and procedures to prevent, detect, contain, and correct security violations, but should make sure that such policies and procedures are actually implemented in their everyday operations.

The P2Y(1) and P2Y(12) receptors mediate autoinhibition of transmitter release in sympathetic innervated tissues.

PubMed

Quintas, Clara; Fraga, Sónia; Gonçalves, Jorge; Queiroz, Glória

2009-12-01

In the sympathetic nervous system, ATP is a co-transmitter and modulator of transmitter release, inhibiting noradrenaline release by acting on P2Y autoreceptors, but in peripheral tissues the subtypes involved have only scarcely been identified. We investigated the identity of the noradrenaline release-inhibiting P2Y subtypes in the epididymal portion of vas deferens and tail artery of the rat. The subtypes operating as autoreceptors, the signalling mechanism and cross-talk with alpha(2)-autoreceptors, was also investigated in the epididymal portion. In both tissues, the nucleotides 2-methylthioATP, 2-methylthioADP, ADP and ATP inhibited noradrenaline release up to 68%, with the following order of potency: 2-methylthioADP=2-methylthioATP>ADP=ATP in the epididymal portion and 2-methylthioADP=2-methylthioATP=ADP>ATP in the tail artery. The selective P2Y(1) antagonist 2'-deoxy-N(6)-methyladenosine 3',5'-bisphosphate (30microM) and the P2Y(12) antagonist 2,2-dimethyl-propionic acid 3-(2-chloro-6-methylaminopurin-9-yl)-2-(2,2-dimethyl-propionyloxymethyl)-propyl ester (30microM) increased noradrenaline release per se by 25+/-8% and 18+/-3%, respectively, in the epididymal portion but not in tail artery. Both antagonists attenuated the effect of nucleotides in the epididymal portion whereas in tail artery only the P2Y(1) antagonist was effective. The agonist of P2Y(1) and P2Y(12) receptors, 2-methylthioADP, caused an inhibition of noradrenaline release that was not prevented by inhibition of phospholipase C or protein kinase C but was abolished by pertussis toxin. 2-methylthioADP and the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine were less potent at inhibiting noradrenaline release under marked influence of alpha(2)-autoinhibition. In both tissues, nucleotides modulate noradrenaline release by activation of inhibitory P2Y(1) receptors but in the epididymal portion P2Y(12) receptors also participate. P2Y(1) and P2Y(12) receptors are coupled to G(i/o)-proteins and operate as autoreceptors in the vas deferens where they interact with alpha(2)-adrenoceptors on the modulation of noradrenaline release.

A Security Checklist for ERP Implementations

ERIC Educational Resources Information Center

Hughes, Joy R.; Beer, Robert

2007-01-01

The EDUCAUSE/Internet2 Computer and Network Security Task Force consulted with IT security professionals on campus about concerns with the current state of security in enterprise resource planning (ERP) systems. From these conversations, it was clear that security issues generally fell into one of two areas: (1) It has become extremely difficult…

77 FR 44306 - Service Delivery Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-27

... SOCIAL SECURITY ADMINISTRATION [Docket No. SSA-2012-0048] Service Delivery Plan AGENCY: Social... publicly available. Do not include in your comments any personal information, such as Social Security... function of the Web page to find docket number SSA-2012-0048. The system will issue you a tracking number...

Security's role in morgue operations: needed--a foolproof plan.

PubMed

White, John M

2012-01-01

If handling the remains of dead patients is a responsibility of your security department, or you are being pressured to take on the role because of budget cuts, the need to anticipate and plan for complications which may arise is critical, the author points out.

29 CFR 2530.201-1 - Coverage; general.

Code of Federal Regulations, 2010 CFR

2010-07-01

... section 3(3) of the Act and § 2510.3-3. (See also the definitions of employee welfare benefit plan... Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR MINIMUM STANDARDS FOR EMPLOYEE PENSION BENEFIT PLANS UNDER THE EMPLOYEE RETIREMENT INCOME SECURITY ACT OF...

76 FR 13442 - Joint Industry Plan; Order Approving Amendment No. 25 to the Joint Self-Regulatory Organization...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-11

..., Consolidation and Dissemination of Quotation and Transaction Information for Nasdaq-Listed Securities Traded on... Exchange, Inc., Financial Industry Regulatory Authority, Inc., International Securities Exchange LLC...-Regulatory Organization Plan Governing the Collection, Consolidation, and Dissemination of Quotation and...

Report: Survey Results on Information Used by Water Utilities to Conduct Vulnerability Assessments

EPA Pesticide Factsheets

Report #2004-M-0001, November 21, 2003. EPA developed a Strategic Plan for Homeland Security (Plan), dated Sept 2002, which states that EPA will work with the States, tribes, drinking water utilities, and others to enhance the security of water utilities.

Security and privacy preserving approaches in the eHealth clouds with disaster recovery plan.

PubMed

Sahi, Aqeel; Lai, David; Li, Yan

2016-11-01

Cloud computing was introduced as an alternative storage and computing model in the health sector as well as other sectors to handle large amounts of data. Many healthcare companies have moved their electronic data to the cloud in order to reduce in-house storage, IT development and maintenance costs. However, storing the healthcare records in a third-party server may cause serious storage, security and privacy issues. Therefore, many approaches have been proposed to preserve security as well as privacy in cloud computing projects. Cryptographic-based approaches were presented as one of the best ways to ensure the security and privacy of healthcare data in the cloud. Nevertheless, the cryptographic-based approaches which are used to transfer health records safely remain vulnerable regarding security, privacy, or the lack of any disaster recovery strategy. In this paper, we review the related work on security and privacy preserving as well as disaster recovery in the eHealth cloud domain. Then we propose two approaches, the Security-Preserving approach and the Privacy-Preserving approach, and a disaster recovery plan. The Security-Preserving approach is a robust means of ensuring the security and integrity of Electronic Health Records, and the Privacy-Preserving approach is an efficient authentication approach which protects the privacy of Personal Health Records. Finally, we discuss how the integrated approaches and the disaster recovery plan can ensure the reliability and security of cloud projects. Copyright © 2016 Elsevier Ltd. All rights reserved.

The European cooperative approach to securing critical information infrastructure.

PubMed

Purser, Steve

2011-10-01

This paper provides an overview of the EU approach to securing critical information infrastructure, as defined in the Action Plan contained in the Commission Communication of March 2009, entitled 'Protecting Europe from large-scale cyber-attacks and disruptions: enhancing preparedness, security and resilience' and further elaborated by the Communication of May 2011 on critical Information infrastructure protection 'Achievements and next steps: towards global cyber-security'. After explaining the need for pan-European cooperation in this area, the CIIP Action Plan is explained in detail. Finally, the current state of progress is summarised together with the proposed next steps.

Marketing Plan for Demonstration and Validation Assets

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

None, None

The National Security Preparedness Project (NSPP), is to be sustained by various programs, including technology demonstration and evaluation (DEMVAL). This project assists companies in developing technologies under the National Security Technology Incubator program (NSTI) through demonstration and validation of technologies applicable to national security created by incubators and other sources. The NSPP also will support the creation of an integrated demonstration and validation environment. This report documents the DEMVAL marketing and visibility plan, which will focus on collecting information about, and expanding the visibility of, DEMVAL assets serving businesses with national security technology applications in southern New Mexico.

Planning Considerations for Secure Network Protocols

DTIC Science & Technology

1999-03-01

distribution / management ) requirements needed to support network security services are examined. The thesis concludes by identifying tactical user network requirements and suggests security issues to be considered in concert with network

6 CFR 27.255 - Recordkeeping requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... audit required under § 27.225(e)) or Security Vulnerability Assessment, a record of the audit, including... retain records of submitted Top-Screens, Security Vulnerability Assessments, Site Security Plans, and all...

Aero-Propulsion Technology (APT) Task V Low Noise ADP Engine Definition Study

NASA Technical Reports Server (NTRS)

Holcombe, V.

2003-01-01

A study was conducted to identify and evaluate noise reduction technologies for advanced ducted prop propulsion systems that would allow increased capacity operation and result in an economically competitive commercial transport. The study investigated the aero/acoustic/structural advancements in fan and nacelle technology required to match or exceed the fuel burned and economic benefits of a constrained diameter large Advanced Ducted Propeller (ADP) compared to an unconstrained ADP propulsion system with a noise goal of 5 to 10 EPNDB reduction relative to FAR 36 Stage 3 at each of the three measuring stations namely, takeoff (cutback), approach and sideline. A second generation ADP was selected to operate within the maximum nacelle diameter constrain of 160 deg to allow installation under the wing. The impact of fan and nacelle technologies of the second generation ADP on fuel burn and direct operating costs for a typical 3000 nm mission was evaluated through use of a large, twin engine commercial airplane simulation model. The major emphasis of this study focused on fan blade aero/acoustic and structural technology evaluations and advanced nacelle designs. Results of this study have identified the testing required to verify the interactive performance of these components, along with noise characteristics, by wind tunnel testing utilizing and advanced interaction rig.

A New Powered Lower Limb Prosthesis Control Framework Based on Adaptive Dynamic Programming.

PubMed

Wen, Yue; Si, Jennie; Gao, Xiang; Huang, Stephanie; Huang, He Helen

2017-09-01

This brief presents a novel application of adaptive dynamic programming (ADP) for optimal adaptive control of powered lower limb prostheses, a type of wearable robots to assist the motor function of the limb amputees. Current control of these robotic devices typically relies on finite state impedance control (FS-IC), which lacks adaptability to the user's physical condition. As a result, joint impedance settings are often customized manually and heuristically in clinics, which greatly hinder the wide use of these advanced medical devices. This simulation study aimed at demonstrating the feasibility of ADP for automatic tuning of the twelve knee joint impedance parameters during a complete gait cycle to achieve balanced walking. Given that the accurate models of human walking dynamics are difficult to obtain, the model-free ADP control algorithms were considered. First, direct heuristic dynamic programming (dHDP) was applied to the control problem, and its performance was evaluated on OpenSim, an often-used dynamic walking simulator. For the comparison purposes, we selected another established ADP algorithm, the neural fitted Q with continuous action (NFQCA). In both cases, the ADP controllers learned to control the right knee joint and achieved balanced walking, but dHDP outperformed NFQCA in this application during a 200 gait cycle-based testing.

Comparison of anthropometric-based equations for estimation of body fat percentage in a normal-weight and overweight female cohort: validation via air-displacement plethysmography.

PubMed

Temple, Derry; Denis, Romain; Walsh, Marianne C; Dicker, Patrick; Byrne, Annette T

2015-02-01

To evaluate the accuracy of the most commonly used anthropometric-based equations in the estimation of percentage body fat (%BF) in both normal-weight and overweight women using air-displacement plethysmography (ADP) as the criterion measure. A comparative study in which the equations of Durnin and Womersley (1974; DW) and Jackson, Pollock and Ward (1980) at three, four and seven sites (JPW₃, JPW₄ and JPW₇) were validated against ADP in three groups. Group 1 included all participants, group 2 included participants with a BMI <25·0 kg/m² and group 3 included participants with a BMI ≥25·0 kg/m². Human Performance Laboratory, Institute for Sport and Health, University College Dublin, Republic of Ireland. Forty-three female participants aged between 18 and 55 years. In all three groups, the %BF values estimated from the DW equation were closer to the criterion measure (i.e. ADP) than those estimated from the other equations. Of the three JPW equations, JPW₃ provided the most accurate estimation of %BF when compared with ADP in all three groups. In comparison to ADP, these findings suggest that the DW equation is the most accurate anthropometric method for the estimation of %BF in both normal-weight and overweight females.

Growth, structural, spectroscopic, thermal, dielectric and optical study of cobalt sulphide-doped ADP crystals

NASA Astrophysics Data System (ADS)

Kochuparampil, A. P.; Joshi, J. H.; Joshi, M. J.

2017-09-01

As ammonium dihydrogen phosphate (ADP) is a popular nonlinear optical crystal, to engineer its linear and nonlinear optical properties, the chalcogenide compound cobalt sulphide (CoS) was doped and the crystals were grown by the slow solvent evaporation method. To increase the solubility of CoS in water, its nanoparticles were synthesized by wet chemical technique using ethylene diamine as the capping agent followed by microwave irradiation. The nanoparticle sample exhibited finite solubility in water and was used to dope in ADP crystals. The powder XRD patterns showed the single phase nature of the doped crystals. The FTIR spectra confirmed the presence of various functional groups and EDAX gave the estimation of Co and S elements. The EPR spectroscopy also confirmed the presence of cobalt in the doped samples. TGA indicated slightly less thermal stability of the doped crystals compared to the pure ADP. The dielectric study was carried out at room temperature in the frequency range from 100Hz to 1MHz. Also, various linear optical parameters were evaluated for pure and doped crystals using UV-Vis spectroscopy. The second harmonic generation (SHG) efficiency of Nd:YAG laser was evaluated by the Kurtz and Parry method for the doped samples, it was found to be slightly lesser than that of the pure ADP crystals.

Effects of excipients and curing process on the abuse deterrent properties of directly compressed tablets.

PubMed

Rahman, Ziyaur; Zidan, Ahmed S; Korang-Yeboah, Maxwell; Yang, Yang; Siddiqui, Akhtar; Shakleya, Diaa; Khan, Mansoor A; Cruz, Celia; Ashraf, Muhammad

2017-01-30

The objective of the present investigation was to understand the effects of excipients and curing process on the abuse deterrent properties (ADP) of Polyox™ based directly compressible abuse deterrent tablet formulations (ADFs). The excipients investigated were lactose (monohydrate or anhydrous), microcrystalline cellulose and hydroxypropyl methylcellulose. The ADPs studied were tablet crush resistance or hardness, particle size distribution following mechanical manipulation, drug extraction in water and alcohol, syringeability and injectability. Other non-ADPs such as surface morphology and tablet dissolution were also studied. It was found that presence of 50% or more of water soluble or swellable excipient in the ADF tablets significantly affected the tablet hardness, particle size distribution following mechanical manipulation and drug extraction while small amount (5%) of excipients had either minimal or no effect on ADPs of these tablets. Addition of high molecular weight HPMC (K 100M) affected syringeability and injectability of ADF. Curing process was found to affect ADPs (hardness, particle size distribution, drug extraction and syringeability and injectability) when compared with uncured tablet. In conclusion, addition of large amount of excipients, especially water soluble ones in Polyox™ based ADF tablets increase the risk of abuse by various routes of administration. Published by Elsevier B.V.

Influence of forced internal air circulation on airflow distribution and heat transfer in a gas double-dynamic solid-state fermentation bioreactor.

PubMed

Chen, Hongzhang; Qin, Lanzhi; Li, Hongqiang

2014-02-01

Internal air circulation affects the temperature field distribution in a gas double-dynamic solid-state fermentation bioreactor (GDSFB). To enhance heat transfer through strengthening internal air circulation in a GDSFB, we put an air distribution plate (ADP) into the bioreactor and studied the effects of forced internal air circulation on airflow, heat transfer, and cellulase activity of Trichoderma viride L3. Results showed that ADP could help form a steady and uniform airflow distribution, and with gas-guide tubes, air reversal was formed inside the bioreactor, thus resulting in a smaller temperature difference between medium and air by enhancing convective heat transfer inside the bioreactor. Using an ADP of 5.35 % aperture ratio caused a 1 °C decrease in the average temperature difference during the solid-state fermentation process of T. viride L3. Meanwhile, the cellulase activity of T. viride L3 increased by 13.5 %. The best heat-transfer effect was attained when using an ADP of 5.35 % aperture ratio and setting the fan power to 125 V (4.81 W) in the gas double-dynamic solid-state fermentation (GDSF) process. An option of suitable aperture ratio and fan power may be conducive to ADPs' industrial amplification.

Permeabilized Rat Cardiomyocyte Response Demonstrates Intracellular Origin of Diffusion Obstacles

PubMed Central

Jepihhina, Natalja; Beraud, Nathalie; Sepp, Mervi; Birkedal, Rikke; Vendelin, Marko

2011-01-01

Intracellular diffusion restrictions for ADP and other molecules have been predicted earlier based on experiments on permeabilized fibers or cardiomyocytes. However, it is possible that the effective diffusion distance is larger than the cell dimensions due to clumping of cells and incomplete separation of cells in fiber preparations. The aim of this work was to check whether diffusion restrictions exist inside rat cardiomyocytes or are caused by large effective diffusion distance. For that, we determined the response of oxidative phosphorylation (OxPhos) to exogenous ADP and ATP stimulation in permeabilized rat cardiomyocytes using fluorescence microscopy. The state of OxPhos was monitored via NADH and flavoprotein autofluorescence. By varying the ADP or ATP concentration in flow chamber, we determined that OxPhos has a low affinity in cardiomyocytes. The experiments were repeated in a fluorometer on cardiomyocyte suspensions leading to similar autofluorescence changes induced by ADP as recorded under the microscope. ATP stimulated OxPhos more in a fluorometer than under the microscope, which was attributed to accumulation of ADP in fluorometer chamber. By calculating the flow profile around the cell in the microscope chamber and comparing model solutions to measured data, we demonstrate that intracellular structures impose significant diffusion obstacles in rat cardiomyocytes. PMID:22067148

The stable and water-soluble neodymium-doped lanthanide fluoride nanoparticles for near infrared probing of copper ion.

PubMed

Xue, Fang-Min; Wang, He-Fang

2012-09-15

Neodymium (Nd(3+)) doped nanomaterials exhibited the unique near infrared (NIR) luminescence properties. However, the application of Nd-doped nanomaterials to chemosensors was rarely explored. Herein, the water-soluble 2-aminoethyl dihydrogen phosphate stabilized Nd-doped LaF(3) (ADP-Nd-LaF(3)) nanoparticles were explored as the NIR probe for chemosensors. The NIR emission intensity at 1061 nm of ADP-Nd-LaF(3) nanoparticles kept stable in the aqueous solution of various pH and coexisting of most common metal ions except copper ion, consequently, the ADP-Nd-LaF(3) nanoparticles were developed as a high selective NIR probe for Cu(II). The NIR emission of ADP-Nd-LaF(3) exhibits a linear quenching response to Cu(II) in the range 5-100 μM, with a detection limit of 0.8 μM. The precision of eleven replicate detections of 5 μM Cu(II) was 0.5% (RSD). The recovery of spiked Cu(II) in human urine and waste water samples ranged from 102 to 109%. The possible mechanism of Cu(II)-induced fluorescence quenching of ADP-Nd-LaF(3) nanoparticles was also discussed. Copyright © 2012 Elsevier B.V. All rights reserved.