A non-conforming 3D spherical harmonic transport solver

International Nuclear Information System (INIS)

Van Criekingen, S.

2006-01-01

A new 3D transport solver for the time-independent Boltzmann transport equation has been developed. This solver is based on the second-order even-parity form of the transport equation. The angular discretization is performed through the expansion of the angular neutron flux in spherical harmonics (PN method). The novelty of this solver is the use of non-conforming finite elements for the spatial discretization. Such elements lead to a discontinuous flux approximation. This interface continuity requirement relaxation property is shared with mixed-dual formulations such as the ones based on Raviart-Thomas finite elements. Encouraging numerical results are presented. (authors)

14 CFR 314.3 - Conformity with subpart A of part 302.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Conformity with subpart A of part 302. 314.3 Section 314.3 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) PROCEDURAL REGULATIONS EMPLOYEE PROTECTION PROGRAM General § 314.3 Conformity with...

14 CFR 325.14 - Conformity with subpart A of part 302.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Conformity with subpart A of part 302. 325.14 Section 325.14 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) PROCEDURAL REGULATIONS ESSENTIAL AIR SERVICE PROCEDURES § 325.14 Conformity with...

Conformational switching in the coiled-coil domains of a proteasomal ATPase regulates substrate processing.

Science.gov (United States)

Snoberger, Aaron; Brettrager, Evan J; Smith, David M

2018-06-18

Protein degradation in all domains of life requires ATPases that unfold and inject proteins into compartmentalized proteolytic chambers. Proteasomal ATPases in eukaryotes and archaea contain poorly understood N-terminally conserved coiled-coil domains. In this study, we engineer disulfide crosslinks in the coiled-coils of the archaeal proteasomal ATPase (PAN) and report that its three identical coiled-coil domains can adopt three different conformations: (1) in-register and zipped, (2) in-register and partially unzipped, and (3) out-of-register. This conformational heterogeneity conflicts with PAN's symmetrical OB-coiled-coil crystal structure but resembles the conformational heterogeneity of the 26S proteasomal ATPases' coiled-coils. Furthermore, we find that one coiled-coil can be conformationally constrained even while unfolding substrates, and conformational changes in two of the coiled-coils regulate PAN switching between resting and active states. This switching functionally mimics similar states proposed for the 26S proteasome from cryo-EM. These findings thus build a mechanistic framework to understand regulation of proteasome activity.

Unbiased simulations reveal the inward-facing conformation of the human serotonin transporter and Na+ ion release

DEFF Research Database (Denmark)

Koldsø, Heidi; Noer, Pernille Rimmer; Grouleff, Julie

2011-01-01

transporter has resulted in homology models of the monoamine transporters. Here we present extended molecular dynamics simulations of an experimentally supported homology model of hSERT with and without the natural substrate yielding a total of more than 1.5 µs of simulation of the protein dimer....... The simulations reveal a transition of hSERT from an outward-facing occluded conformation to an inward-facing conformation in a one-substrate-bound state. Simulations with a second substrate in the proposed symport effector site did not lead to conformational changes associated with translocation. The central...... substrate binding site becomes fully exposed to the cytoplasm leaving both the Na+-ion in the Na2-site and the substrate in direct contact with the cytoplasm through water interactions. The simulations reveal how sodium is released and show indications of early events of substrate transport. The notion...

Structure of the cystic fibrosis transmembrane conductance regulator in the inward-facing conformation revealed by single particle electron microscopy

Directory of Open Access Journals (Sweden)

Ateeq Al-Zahrani

2015-05-01

Full Text Available The most common inherited disease in European populations is cystic fibrosis. Mutations in the gene lead to loss of function of the cystic fibrosis transmembrane conductance regulator protein (CFTR. CFTR is a member of the ATP-binding cassette family of membrane proteins that mostly act as active transporters using ATP to move substances across membranes. These proteins undergo large conformational changes during the transport cycle, consistent with an inward-facing to outward-facing translocation mechanism that was originally proposed by Jardetzky. CFTR is the only member of this family of proteins that functions as an ion channel, and in this case ATP and phosphorylation of a regulatory domain controls the opening of the channel. In this article we describe the inward-facing conformation of the protein and show it can be modulated by the presence of a purified recombinant NHERF1-PDZ1 domain that binds with high affinity to the CFTR C-terminal PDZ motif (-QDTRL. ATP hydrolysis activity of CFTR can also be modulated by glutathione, which we postulate may bind to the inward-facing conformation of the protein. A homology model for CFTR, based on a mitochondrial ABC transporter of glutathione in the inward-facing configuration has been generated. The map and the model are discussed with respect to the biology of the channel and the specific relationship between glutathione levels in the cell and CFTR. Finally, disease-causing mutations are mapped within the model and discussed in terms of their likely physiological effects.

Management system for regulating transport of radioactive material

International Nuclear Information System (INIS)

Lopez Vietri, Jorge; Capadona, Nancy; Barenghi, Leonardo

2008-01-01

Full text: The objective of this paper is to describe the main characteristics and fundamentals of the Nuclear regulatory Authority's (Autoridad Regulatoria Nuclear, ARN) management system applied to the regulation of transport of radioactive material, in Argentina. In the frame of ARN's quality policy, 'Protection against ionizing radiation on transport of radioactive materials' was selected as one of the regulatory processes, named TRM process from now on. ARN's quality management system is integrally based on ISO 9000 system addressed to help organizations in designing and implementing their quality management systems. TRM process was split into five sub processes in order to facilitate the implementation of quality system. Such sub processes were defined taking account of the main functions developed by ARN in the branch of safe transport of radioactive materials and are listed below: 1) Development and updating of standards and regulatory guides; 2) Licensing of packages, special radioactive materials and consignments of radioactive materials; 3) Compliance assurance during the transport of radioactive materials, and 4) Training, advising and communications. For each of these sub processes were specified their objectives, inputs, activities and outputs, the clients and stakeholders, responsibilities, supporting documents, control of documents and records, control of non-conformances, monitoring and measurements, audits, feedback and improvement. It was decided to develop a quality plan to organize and manage activities to meet quality requirements, to optimize the use of limited resources of the organization and to be used as a basis for monitoring and assessing compliance with the requirements, both internal and external. Supporting documents for sub processes were issued, validated, reviewed and improved as an essential point to implement continuous improving. Simultaneously, some indexes were defined to monitor and measure the sub processes as a way to show

Transportation Conformity Training and Presentations

Science.gov (United States)

EPA's OTAQ has provided multiple conformity training sessions in the past to assist state and local governments in implementing conformity requirements. As training information is prepared for other venues, it will be posted on this page.

Conformation regulation of the X chromosome inactivation center: a model.

Directory of Open Access Journals (Sweden)

Antonio Scialdone

2011-10-01

Full Text Available X-Chromosome Inactivation (XCI is the process whereby one, randomly chosen X becomes transcriptionally silenced in female cells. XCI is governed by the Xic, a locus on the X encompassing an array of genes which interact with each other and with key molecular factors. The mechanism, though, establishing the fate of the X's, and the corresponding alternative modifications of the Xic architecture, is still mysterious. In this study, by use of computer simulations, we explore the scenario where chromatin conformations emerge from its interaction with diffusing molecular factors. Our aim is to understand the physical mechanisms whereby stable, non-random conformations are established on the Xic's, how complex architectural changes are reliably regulated, and how they lead to opposite structures on the two alleles. In particular, comparison against current experimental data indicates that a few key cis-regulatory regions orchestrate the organization of the Xic, and that two major molecular regulators are involved.

A dualistic conformational response to substrate binding in the human serotonin transporter reveals a high affinity state for serotonin

DEFF Research Database (Denmark)

Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida

2015-01-01

Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across...... the membrane. Our understanding of these conformational changes is mainly based on crystal structures of a bacterial homolog in various conformations, derived homology models of eukaryotic neurotransmitter transporters, and substituted cysteine accessibility method of SERT. However, the dynamic changes...

Lipid Regulated Intramolecular Conformational Dynamics of SNARE-Protein Ykt6

Science.gov (United States)

Dai, Yawei; Seeger, Markus; Weng, Jingwei; Song, Song; Wang, Wenning; Tan, Yan-Wen

2016-08-01

Cellular informational and metabolic processes are propagated with specific membrane fusions governed by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNARE). SNARE protein Ykt6 is highly expressed in brain neurons and plays a critical role in the membrane-trafficking process. Studies suggested that Ykt6 undergoes a conformational change at the interface between its longin domain and the SNARE core. In this work, we study the conformational state distributions and dynamics of rat Ykt6 by means of single-molecule Förster Resonance Energy Transfer (smFRET) and Fluorescence Cross-Correlation Spectroscopy (FCCS). We observed that intramolecular conformational dynamics between longin domain and SNARE core occurred at the timescale ~200 μs. Furthermore, this dynamics can be regulated and even eliminated by the presence of lipid dodecylphoshpocholine (DPC). Our molecular dynamic (MD) simulations have shown that, the SNARE core exhibits a flexible structure while the longin domain retains relatively stable in apo state. Combining single molecule experiments and theoretical MD simulations, we are the first to provide a quantitative dynamics of Ykt6 and explain the functional conformational change from a qualitative point of view.

Effect of the proposed adoption of the International Atomic Energy Agency regulations, 1985 revision, on the U.S. radioactive waste transportation industry

International Nuclear Information System (INIS)

Benda, G.A.; Lewis, M.S.; Allen, J.H.

1989-01-01

The Nuclear Regulatory Commission (NRC) is proposing changes to 10CFR 71 transportation regulations to achieve compatibility with the 1985 IAEA regulations. The intent of these changes is to be more compatible with the international standard on shipping containers, package requirements, and performance criteria. The NRC has, however, modified part of its regulations to restrict the packaging of LSA by limiting the total activity rather than adopting the IAEA standard. This paper addresses how the proposed regulations will affect the low-level radioactive waste transportation industry. It describes the impacts on the transportation industry in three major areas-IAEA consistency, economic impact, and risk assessment. Available transport data from the Barnwell disposal site was used in the analysis of the proposed changes. The impacts addressed include possible increased radiation exposures, transportation risks and liability, transportation and processing costs, and waste disposal costs resulting in little health and safety benefit. Although the health and safety benefits of any change to the current regulations are minimal, suggested alternatives to the proposed regulations are discussed that more closely conform with the international standards while still maintaining health and safety

Boron transport in plants: co-ordinated regulation of transporters

Science.gov (United States)

Miwa, Kyoko; Fujiwara, Toru

2010-01-01

Background The essentiality of boron (B) for plant growth was established >85 years ago. In the last decade, it has been revealed that one of the physiological roles of B is cross-linking the pectic polysaccharide rhamnogalacturonan II in primary cell walls. Borate cross-linking of pectic networks serves both for physical strength of cell walls and for cell adhesion. On the other hand, high concentrations of B are toxic to plant growth. To avoid deficiency and toxicity problems, it is important for plants to maintain their tissue B concentrations within an optimum range by regulating transport processes. Boron transport was long believed to be a passive, unregulated process, but the identification of B transporters has suggested that plants sense and respond to the B conditions and regulate transporters to maintain B homeostasis. Scope Transporters responsible for efficient B uptake by roots, xylem loading and B distribution among leaves have been described. These transporters are required under B limitation for efficient acquisition and utilization of B. Transporters important for tolerating high B levels in the environment have also been identified, and these transporters export B from roots back to the soil. Two types of transporters are involved in these processes: NIPs (nodulin-26-like intrinsic proteins), boric acid channels, and BORs, B exporters. It is demonstrated that the expression of genes encoding these transporters is finely regulated in response to B availability in the environment to ensure tissue B homeostasis. Furthermore, plants tolerant to stress produced by low B or high B in the environment can be generated through altered expression of these transporters. Conclusions The identification of the first B transporter led to the discovery that B transport was a process mediated not only by passive diffusion but also by transporters whose activity was regulated in response to B conditions. Now it is evident that plants sense internal and external B

Relationship between conformational changes in the dopamine transporter and cocaine-like subjective effects of uptake inhibitors

DEFF Research Database (Denmark)

Løland, Claus Juul; Desai, Rajeev I; Zou, Mu-Fa

2007-01-01

Cocaine exerts its stimulatory effect by inhibiting the dopamine transporter (DAT). However, novel benztropine- and rimcazole-based inhibitors show reduced stimulant effects compared with cocaine, despite higher affinity and selectivity for DAT. To investigate possible mechanisms, we compared...... the extracellular transporter gate is open but inaccessible when it is closed. The data indicated that cocaine analogs bind an open conformation, whereas benztropine and rimcazole analogs bind a closed conformation. Next, we investigated the changes in inhibition potency of [(3)H]dopamine uptake of the compounds...... at a mutant DAT (Y335A) characterized by a global change in the conformational equilibrium. We observed a close relationship between the decrease in potencies of inhibitors at this mutant and cocaine-like responding in rats trained to discriminate cocaine from saline injections. Our data suggest...

Unbiased simulations reveal the inward-facing conformation of the human serotonin transporter and Na(+ ion release.

Directory of Open Access Journals (Sweden)

Heidi Koldsø

2011-10-01

Full Text Available Monoamine transporters are responsible for termination of synaptic signaling and are involved in depression, control of appetite, and anxiety amongst other neurological processes. Despite extensive efforts, the structures of the monoamine transporters and the transport mechanism of ions and substrates are still largely unknown. Structural knowledge of the human serotonin transporter (hSERT is much awaited for understanding the mechanistic details of substrate translocation and binding of antidepressants and drugs of abuse. The publication of the crystal structure of the homologous leucine transporter has resulted in homology models of the monoamine transporters. Here we present extended molecular dynamics simulations of an experimentally supported homology model of hSERT with and without the natural substrate yielding a total of more than 1.5 µs of simulation of the protein dimer. The simulations reveal a transition of hSERT from an outward-facing occluded conformation to an inward-facing conformation in a one-substrate-bound state. Simulations with a second substrate in the proposed symport effector site did not lead to conformational changes associated with translocation. The central substrate binding site becomes fully exposed to the cytoplasm leaving both the Na(+-ion in the Na2-site and the substrate in direct contact with the cytoplasm through water interactions. The simulations reveal how sodium is released and show indications of early events of substrate transport. The notion that ion dissociation from the Na2-site drives translocation is supported by experimental studies of a Na2-site mutant. Transmembrane helices (TMs 1 and 6 are identified as the helices involved in the largest movements during transport.

Substrate binding accelerates the conformational transitions and substrate dissociation in multidrug efflux transporter AcrB

Directory of Open Access Journals (Sweden)

Beibei eWang

2015-04-01

Full Text Available The tripartite efflux pump assembly AcrAB-TolC is the major multidrug resistance transporter in E. coli. The inner membrane transporter AcrB is a homotrimer, energized by the proton movement down the transmembrane electrochemical gradient. The asymmetric crystal structures of AcrB with three monomers in distinct conformational states (access (A, binding (B and extrusion (E support a functional rotating mechanism, in which each monomer of AcrB cycles among the three states in a concerted way. However, the relationship between the conformational changes during functional rotation and drug translocation has not been totally understood. Here, we explored the conformational changes of the AcrB homotrimer during the ABE→BEA transition in different substrate-binding states using targeted MD simulations. It was found that the dissociation of substrate from the distal binding pocket of B monomer is closely related to the concerted conformational changes in the translocation pathway, especially the side chain reorientation of Phe628 and Tyr327. A second substrate binding at the proximal binding pocket of A monomer evidently accelerates the conformational transitions as well as substrate dissociation in B monomer. The acceleration effect of the multi-substrate binding mode provides a molecular explanation for the positive cooperativity observed in the kinetic studies of substrate efflux and deepens our understanding of the functional rotating mechanism of AcrB.

Circadian Regulation of Glutamate Transporters

Directory of Open Access Journals (Sweden)

Donají Chi-Castañeda

2018-06-01

Full Text Available L-glutamate is the major excitatory amino acid in the mammalian central nervous system (CNS. This neurotransmitter is essential for higher brain functions such as learning, cognition and memory. A tight regulation of extra-synaptic glutamate levels is needed to prevent a neurotoxic insult. Glutamate removal from the synaptic cleft is carried out by a family of sodium-dependent high-affinity transporters, collectively known as excitatory amino acid transporters. Dysfunction of glutamate transporters is generally involved in acute neuronal injury and neurodegenerative diseases, so characterizing and understanding the mechanisms that lead to the development of these disorders is an important goal in the design of novel treatments for the neurodegenerative diseases. Increasing evidence indicates glutamate transporters are controlled by the circadian system in direct and indirect manners, so in this contribution we focus on the mechanisms of circadian regulation (transcriptional, translational, post-translational and post-transcriptional regulation of glutamate transport in neuronal and glial cells, and their consequence in brain function.

Transportation of radioactive materials. Safety and regulation

International Nuclear Information System (INIS)

Niel, Jean-Christophe

2013-01-01

This engineering-oriented publication first presents fluxes and risks related to the transportation of radioactive materials: fluxes, risks, in-depth defence, and parcel typology. The author then describes the elaboration process for transportation regulations: IAEA recommendations for the transportation of radioactive materials and their review process, IAEA recommendations for modal regulations. He presents the French transportation regulation framework: evolutions of IAEA recommendations, case of aerial transport, and case of maritime transport. The next part addresses the specific case of the transportation of uranium hexafluoride. The last part addresses incidents and accidents occurring during transportation: declarations to be made, brief presentations of several examples of incidents and accidents

Regulations for the safe transport of radioactive materials

International Nuclear Information System (INIS)

Kgogo, Obonye

2016-04-01

The report provides insight and investigates whether Transport Regulations in Botswana follow international standards for transport of radioactive material. Radioactive materials are very useful in most of our activities and are manufactured in different countries, therefore end up traversing from one country to another and being transported in national roads .The IAEA regulation for the Transport of radioactive material is used as the reference guideline in this study. The current Regulations for Transport of radioactive material in Botswana do not cover all factors which need to be considered when transporting radioactive although they refer to IAEA regulations. Basing on an inadequacy of the regulations and category of radioactive materials in the country recommendations were made concerning security, packaging and worker training's. The regulations for the Transport of radioactive material in Botswana need to be reviewed and updated so that they can relate to international standard. (au)

Transport regulation for radioactive materials

International Nuclear Information System (INIS)

Ha Vinh Phuong.

1986-01-01

Taking into account the specific dangers associated with the transport of radioactive materials (contamination, irradiation, heat, criticality), IAEA regulations concerning technical specifications and administrative procedures to ward off these dangers are presented. The international agreements related to the land transport, maritime transport and air transport of radioactive materials are also briefly reviewed

A Dualistic Conformational Response to Substrate Binding in the Human Serotonin Transporter Reveals a High Affinity State for Serotonin*

Science.gov (United States)

Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida; Wiborg, Ove; Sinning, Steffen

2015-01-01

Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across the membrane. Our understanding of these conformational changes is mainly based on crystal structures of a bacterial homolog in various conformations, derived homology models of eukaryotic neurotransmitter transporters, and substituted cysteine accessibility method of SERT. However, the dynamic changes that occur in the human SERT upon binding of ions, the translocation of substrate, and the role of cholesterol in this interplay are not fully elucidated. Here we show that serotonin induces a dualistic conformational response in SERT. We exploited the substituted cysteine scanning method under conditions that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation. Furthermore, we found that membrane cholesterol plays a role in the dualistic conformational response in SERT induced by serotonin. Our results indicate the existence of a subpopulation of SERT responding differently to serotonin binding than hitherto believed and that membrane cholesterol plays a role in this subpopulation of SERT. PMID:25614630

Substrate and Inhibitor-Specific Conformational Changes in the Human Serotonin Transporter Revealed by Voltage-Clamp Fluorometry

DEFF Research Database (Denmark)

Söderhielm, Pella C; Andersen, Jacob; Munro, Lachlan

2015-01-01

of TM6, Ala419 in the interface between TM8 and extracellular loop (EL) 4, and Leu481 in EL5. The reporter positions were used for time-resolved measurement of conformational changes during 5-HT transport and binding of cocaine and the selective serotonin reuptake inhibitors fluoxetine and escitalopram...... changes overall, which included movements within or around TM1b, EL4, and EL5. Taken together, our data lead us to suggest that competitive inhibitors stabilize hSERT in a state that is different from the apo outward-open conformation as well as inward-facing conformations....

Rapid transporter regulation prevents substrate flow traffic jams in boron transport

Science.gov (United States)

Sotta, Naoyuki; Duncan, Susan; Tanaka, Mayuki; Sato, Takafumi

2017-01-01

Nutrient uptake by roots often involves substrate-dependent regulated nutrient transporters. For robust uptake, the system requires a regulatory circuit within cells and a collective, coordinated behaviour across the tissue. A paradigm for such systems is boron uptake, known for its directional transport and homeostasis, as boron is essential for plant growth but toxic at high concentrations. In Arabidopsis thaliana, boron uptake occurs via diffusion facilitators (NIPs) and exporters (BORs), each presenting distinct polarity. Intriguingly, although boron soil concentrations are homogenous and stable, both transporters manifest strikingly swift boron-dependent regulation. Through mathematical modelling, we demonstrate that slower regulation of these transporters leads to physiologically detrimental oscillatory behaviour. Cells become periodically exposed to potentially cytotoxic boron levels, and nutrient throughput to the xylem becomes hampered. We conclude that, while maintaining homeostasis, swift transporter regulation within a polarised tissue context is critical to prevent intrinsic traffic-jam like behaviour of nutrient flow. PMID:28870285

A non-conforming generalization of Raviart-Thomas elements to the spherical harmonic form of the even-parity neutron transport equation

Energy Technology Data Exchange (ETDEWEB)

Van Criekingen, S. [Commissariat a l' energie atomique (CEA-Saclay), DEN/DM2S/SERMA/LENR (Bat 470), 91191 Gif-sur-Yvette Cedex (France)]. E-mail: serge.van-criekingen@cea.fr

2006-05-15

The Raviart-Thomas finite elements provide an appropriate spatial discretization of the mixed-dual form of the diffusion equation. This discretization can then be coupled to an efficient solution method. The high performances achieved by such an approach triggered research on its possible generalization to the transport equation using a spherical harmonic (or P {sub N}) angular approximation. In view of the difficulty of developing a straightforward generalization within the mixed-dual framework, we here consider 2D non-conforming (i.e., allowing interface discontinuities) finite elements coupled to the second-order form of the transport equation. This non-conforming approach keeps the mixed-dual property of the relaxation of the flux interface continuity constraint. We investigate different non-conforming elements and compare them to the well-known Lagrangian conforming elements.

A non-conforming generalization of Raviart-Thomas elements to the spherical harmonic form of the even-parity neutron transport equation

International Nuclear Information System (INIS)

Van Criekingen, S.

2006-01-01

The Raviart-Thomas finite elements provide an appropriate spatial discretization of the mixed-dual form of the diffusion equation. This discretization can then be coupled to an efficient solution method. The high performances achieved by such an approach triggered research on its possible generalization to the transport equation using a spherical harmonic (or P N ) angular approximation. In view of the difficulty of developing a straightforward generalization within the mixed-dual framework, we here consider 2D non-conforming (i.e., allowing interface discontinuities) finite elements coupled to the second-order form of the transport equation. This non-conforming approach keeps the mixed-dual property of the relaxation of the flux interface continuity constraint. We investigate different non-conforming elements and compare them to the well-known Lagrangian conforming elements

Regulation of auxin transport during gravitropism

Science.gov (United States)

Rashotte, A.; Brady, S.; Kirpalani, N.; Buer, C.; Muday, G.

Plants respond to changes in the gravity vector by differential growth across the gravity-stimulated organ. The plant hormone auxin, which is normally basipetally transported, changes in direction and auxin redistribution has been suggested to drive this differential growth or gravitropism. The mechanisms by which auxin transport directionality changes in response to a change in gravity vector are largely unknown. Using the model plant, Arabidopsis thaliana, we have been exploring several regulatory mechanisms that may control auxin transport. Mutations that alter protein phosphorylation suggest that auxin transport in arabidopsis roots may be controlled via phosphorylation and this signal may facilitate gravitropic bending. The protein kinase mutant pinoid (pid9) has reduced auxin transport; whereas the protein phosphatase mutant, rcn1, has elevated transport, suggesting reciprocal regulation of auxin transport by reversible protein phosphorylation. In both of these mutants, the auxin transport defects are accompanied by gravitropic defects, linking phosphorylation signaling to gravity-induced changes in auxin transport. Additionally, auxin transport may be regulated during gravity response by changes in an endogenous auxin efflux inhibitor. Flavonoids, such as quercetin and kaempferol, have been implicated in regulation of auxin transport in vivo and in vitro. Mutants that make no flavonoids have reduced root gravitropic bending. Furthermore, changes in auxin-induced gene expression and flavonoid accumulation patterns have been observed during gravity stimulation. Current studies are examining whether there are spatial and temporal changes in flavonoid accumulation that precede gravitropic bending and whether the absence of these changes are the cause of the altered gravity response in plants with mutations that block flavonoid synthesis. These results support the idea that auxin transport may be regulated during gravity response by several mechanisms including

The international radioactive transportation regulations: A model for national regulations

International Nuclear Information System (INIS)

Pope, R.B.; Rawl, R.R.

1990-06-01

The International Atomic Energy Agency's (IAEA) Regulations for the Safe Transport of Radioactive Material, Safety Series No. 6 (herein after denoted as the ''International Regulations'') serve as the model for the regulations for individual countries and international modal organizations controlling the packaging and transportation of radioactive materials. The purpose of this paper is to outline the background and history of the International Regulations, the general principles behind the requirements of the International Regulations, the structure and general contents of the latest edition of the International Regulations, and the roles of various international bodies in the development and implementation of the International Regulations and the current status of regulatory and supportive document development at both the international and domestic level. This review will provide a basis for users and potential users to better understand the source and application of the International Regulations. 1 tab

Regulators of Slc4 bicarbonate transporter activity

Directory of Open Access Journals (Sweden)

Ian M. Thornell

2015-06-01

Full Text Available The Slc4 family of transporters is comprised of anion exchangers (AE1-4, Na-coupled bicarbonate transporters (NCBTs including electrogenic Na/bicarbonate cotransporters (NBCe1 and NBCe2, electroneutral Na/bicarbonate cotransporters (NBCn1 and NBCn2, and the electroneutral Na-driven Cl-bicarbonate exchanger (NDCBE, as well as a borate transporter (BTR1. These transporters regulate intracellular pH (pHi and contribute to steady-state pHi, but are also involved in other physiological processes including CO2 carriage by red blood cells and solute secretion/reabsorption across epithelia. Acid-base transporters function as either acid extruders or acid loaders, with the Slc4 proteins moving HCO3– either into or out of cells. According to results from both molecular and functional studies, multiple Slc4 proteins and/or associated splice variants with similar expected effects on pHi are often found in the same tissue or cell. Such apparent redundancy is likely to be physiologically important. In addition to regulating pHi, a HCO3– transporter contributes to a cell’s ability to fine tune the intracellular regulation of the cotransported/exchanged ion(s (e.g., Na+ or Cl–. In addition, functionally similar transporters or splice variants with different regulatory profiles will optimize pH physiology and solute transport under various conditions or within subcellular domains. Such optimization will depend on activated signaling pathways and transporter expression profiles. In this review, we will summarize and discuss both classical and more recently identified regulators of the Slc4 proteins. Some of these regulators include traditional second messengers, lipids, binding proteins, autoregulatory domains, and less conventional regulators. The material presented will provide insight into the diversity and physiological significance of multiple members within the Slc4 gene family.

Strategic regulation of gas transport

International Nuclear Information System (INIS)

Nese, Gjermund; Straume, Odd Rune

2005-01-01

The basis of the article has been the steadily increasing focus particularly from EU, on increased competition in the natural gas markets. This could influence the profit distribution between the gas producing and consuming counties which is an important problem situation for Norway as a gas producer. The gas market value chain consist of three parts (production, transport and distribution). How the countries may use strategic regulation of the transport tariff for the transport and distribution systems in order to move as much as possible of the total profit to the part of the value chain in control is studied. The focus has been on how increased competition influences the incentives of the authorities through low or high transport tariff and to what extent increased competition influences the welfare level in the producer and consumer counties when strategic regulations of the transport occur. The analysis is based on a theoretical model developed in 2005. Some central mechanisms related to the natural gas market are mapped and Norway may counteract some negative effects of liberalisation of the European gas market through strategic adaptation of the transport tariff to the Norwegian gas transport systems

CONFORMITY TO OCCUPATIONAL SAFETY AND HEALTH REGULATIONS IN MALAYSIAN SMALL AND MEDIUM ENTERPRISES

OpenAIRE

Baba Md Deros; Ahmad Rasdan Ismail; Jaharah A. Ghani; Mohd Yusri Mohd Yusof

2014-01-01

Regulation on occupational safety and health in Malaysia had evolved from the prescriptive factory and machinery act to a self-regulated occupational safety and health act. However, from the authors’ observation the high standards of occupational safety and health culture that surpass the legal requirement were not widely practiced by Small and Medium Enterprises (SMEs). The two main objectives of this study are: First, first, to identify and determine the level of conformity and second...

Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding

Science.gov (United States)

Danilov, Sergei M.; Lünsdorf, Heinrich; Akinbi, Henry T.; Nesterovitch, Andrew B.; Epshtein, Yuliya; Letsiou, Eleftheria; Kryukova, Olga V.; Piegeler, Tobias; Golukhova, Elena Z.; Schwartz, David E.; Dull, Randal O.; Minshall, Richard D.; Kost, Olga A.; Garcia, Joe G. N.

2016-01-01

Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients. PMID:27734897

CLP Regulation and the transport of dangerous goods

Directory of Open Access Journals (Sweden)

Sergio Benassai

2011-01-01

Full Text Available Regulations concerning different modes of transport of dangerous goods are well harmonized at global level: they were then looked at as a model for developing Globally Harmonized System of Classification and Labelling of Chemicals (GHS, (on which CLP Regulations is based. Transport regulations do not cover some hazard classes, such as germ cell mutagenicity, carcinogenicity, reproductive toxicity, having been evaluated that such hazards are not relevant in transport because in general, in case of accident, no repeated and prolonged exposure takes place. Other differences with CLP Regulation are related to the use of "building block approach". Transport labels, which were used as a basis for GHS, can be used, instead of CLP pictograms, on packages during transport.

Preparing regulations for radioactive waste transport

International Nuclear Information System (INIS)

Robles, Fernando

2002-01-01

The article describes the diferent stages in preparing the regulation on safe transport of radioactive materials. The first stage was the support given by the International Atomic Energy Agency in to provide expertise in drafting the national regulation on this matter. The draft is based on the publication from IAEA Regulation on the safe transport of radioactive materials. Also a description of activities made by the Radiation Protection Department of the Energy Directorate of Guatemala is made by the Chief of the Department Dr. Fernando Robles

Regulations concerning the transport of nuclear fuel materials outside the works or the enterprise

International Nuclear Information System (INIS)

1981-01-01

This rule is established under the provisions of the law concerning the regulation of nuclear raw materials, nuclear fuel materials and nuclear reactors and the ordinance for its execution, and to enforce the law. Basic terms are defined, such as vehicle transport, simplified transport, nuclear fuel transport goods, exclusive loading, worker, cumulative dose and exposure radiation dose. Nuclear fuel transport goods are classified into types of L, A, BM and BU according to their radioactivities. Radiation dose rate shall not exceed 0.5 milli-rem an hour on the surface of the type L, and 200 milli-rem an hour on the surface of the type A. For the type BM, the rate shall not surpass 1,000 milli-rem an hour at the distance of 1 meter from the surface in the special test conditions. The transport goods of fissile materials must not reach criticality on the way, but also shall conform to the stipulated technical standards. The particular things contaminated by nuclear fuel materials can be transported without specifying as nuclear fuel transport goods, and their radiation dose rate shall not go beyond 0.5 milli-rem an hour on the surface. The transport by special measures, the technical standards of simplified transport and measures to be taken in danger in transit are defined, respectively.(Okada, K.)

The expression and regulation of glucose transporters in tumor cells

Directory of Open Access Journals (Sweden)

Pengfei Zhao

2016-12-01

Full Text Available Glucose transporter proteins are involved in many physiological and biochemical processes. In particular, the high expressions of sodium-glucose cotransporter and glucose transporter proteins in tumor cells show that these two transporters play a key role in tumor cell metabolism. Studying the crystal structure and conformation of human glucose transporter proteins has enabled the development of drugs based on specific binding sites, opening up a new path towards more effective cancer treatments. This mini review serves to summarize our existing understanding of the metabolic pathways of tumor cells, focusing on the roles of glucose transporter proteins.

A Quantitative bgl Operon Model for E. coli Requires BglF Conformational Change for Sugar Transport

Science.gov (United States)

Chopra, Paras; Bender, Andreas

The bgl operon is responsible for the metabolism of β-glucoside sugars such as salicin or arbutin in E. coli. Its regulatory system involves both positive and negative feedback mechanisms and it can be assumed to be more complex than that of the more closely studied lac and trp operons. We have developed a quantitative model for the regulation of the bgl operon which is subject to in silico experiments investigating its behavior under different hypothetical conditions. Upon administration of 5mM salicin as an inducer our model shows 80-fold induction, which compares well with the 60-fold induction measured experimentally. Under practical conditions 5-10mM inducer are employed, which is in line with the minimum inducer concentration of 1mM required by our model. The necessity of BglF conformational change for sugar transport has been hypothesized previously, and in line with those hypotheses our model shows only minor induction if conformational change is not allowed. Overall, this first quantitative model for the bgl operon gives reasonable predictions that are close to experimental results (where measured). It will be further refined as values of the parameters are determined experimentally. The model was developed in Systems Biology Markup Language (SBML) and it is available from the authors and from the Biomodels repository [www.ebi.ac.uk/biomodels].

Export and import. Conformity with regulations

International Nuclear Information System (INIS)

Shapar, M.

1976-01-01

Since the division of the former US Atomic Energy Commission's tasks, the regulation and control of import and export of nuclear materials and equipment has become the responsability of the Nuclear Regulatory Commission (NRC). The import and export of nuclear fuels, equipment and reactors are therefore subject to prior licensing by the Commission. This requirement aims to guarantee that such activities will not create serious hazards for defense and national safety, and that the exported products will not be diverted from their peaceful uses. The relevant applicable legal provisions are based on the Atomic Energy Act of 1954 and on the detailed regulations issued by the Commission. Under the pressure of public opinion, there is a current tendency to restrict these activities because of the hazards they present, in particular during transport, until the Commission has completed all the necessary studies. (NEA) [fr

Transportation conformity particulate matter hot-spot air quality modeling.

Science.gov (United States)

2013-07-01

In light of the new development in particulate matter (PM) hot-spot regulations and Illinois Department : of Transportation (IDOT)s National Environmental Policy Act (NEPA) documentation requirements, : this project is intended to (1) perform and ...

Regulation of transport processes across the tonoplast

Science.gov (United States)

Neuhaus, H. Ekkehard; Trentmann, Oliver

2014-01-01

In plants, the vacuole builds up the cellular turgor and represents an important component in cellular responses to diverse stress stimuli. Rapid volume changes of cells, particularly of motor cells, like guard cells, are caused by variation of osmolytes and consequently of the water contents in the vacuole. Moreover, directed solute uptake into or release out of the large central vacuole allows adaptation of cytosolic metabolite levels according to the current physiological requirements and specific cellular demands. Therefore, solute passage across the vacuolar membrane, the tonoplast, has to be tightly regulated. Important principles in vacuolar transport regulation are changes of tonoplast transport protein abundances by differential expression of genes or changes of their activities, e.g., due to post-translational modification or by interacting proteins. Because vacuolar transport is in most cases driven by an electro-chemical gradient altered activities of tonoplast proton pumps significantly influence vacuolar transport capacities. Intense studies on individual tonoplast proteins but also unbiased system biological approaches have provided important insights into the regulation of vacuolar transport. This short review refers to selected examples of tonoplast proteins and their regulation, with special focus on protein phosphorylation. PMID:25309559

Coarse-grained Simulations of Sugar Transport and Conformational Changes of Lactose Permease

Science.gov (United States)

Liu, Jin; Jewel, S. M. Yead; Dutta, Prashanta

2016-11-01

Escherichia coli lactose permease (LacY) actively transports lactose and other galactosides across cell membranes through lactose/H+ symport process. Lactose/H+ symport is a highly complex process that involves sugar translocation, H+ transfer, as well as large-scale protein conformational changes. The complete picture of lactose/H+ symport is largely unclear due to the complexity and multiscale nature of the process. In this work, we develop the force field for sugar molecules compatible with PACE, a hybrid and coarse-grained force field that couples the united-atom protein models with the coarse-grained MARTINI water/lipid. After validation, we implement the new force field to investigate the transport of a β-D-galactopyranosyl-1-thio- β-D-galactopyranoside (TDG) molecule across a wild-type LacY during lactose/H+ symport process. Results show that the local interactions between TDG and LacY at the binding pocket are consistent with the X-ray experiment. Protonation of Glu325 stabilizes the TDG and inward-facing conformation of LacY. Protonation of Glu269 induces a dramatic protein structural reorganization and causes the expulsion of TDG from LacY to both sides of the membrane. The structural changes occur primarily in the N-terminal domain of LacY. This work is supported by NSF Grants: CBET-1250107 and CBET -1604211.

Provision of transport packaging for radioactive materials

International Nuclear Information System (INIS)

1981-04-01

The safe transport of radioactive materials is governed by various regulations based on International Atomic Energy Agency Regulations. This code of practice is a supplement to the regulations, its objects being (a) to advise designers of packaging on the technical features necessary to conform to the regulations, and (b) to outline the requirements for obtaining approval of package designs from the competent authority. (U.K.)

Regulations related to the transport of radioactive material in Brazil

International Nuclear Information System (INIS)

Sahyun, Adelia; Sordi, Gian-Maria A.A.; Sanches, Matias P.

2001-01-01

The transport of radioactive material has raised great interest on the part of national regulatory authorities, thus resulting in a safety measures improvement for all kinds of transportation. The transport of radioactive material is regulated by safety criteria much more than those applied to conventional hazardous material. All radioactive material transportation run in Brazilian territory must be in accordance with what is established by the CNEN-NE 5.01 - Transport of Radioactive Material. There are other national and international regulations for radioactive material transportation, which have to be accomplished with and adopted during the operation of radioactive material transportation. The aim of this paper is to verify the criteria set up in the existing regulations and propose a consensus for all the intervening organizations in the regulation process for land, air or sea transportation. This kind of transportation can not depend on the efforts of only one person, a group of workers or even any governmental body, but must be instead a shared responsibility among workers, transport firms and all regulative transportation organizations. (author)

Regulations related to the transport of radioactive material in Brazil

Energy Technology Data Exchange (ETDEWEB)

Sahyun, Adelia; Sordi, Gian-Maria A.A. [ATOMO Radioprotecao e Seguranca Nuclear, Sao Paulo, SP (Brazil)]. E-mail: atomo@atomo.com.br; Sanches, Matias P. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil)]. E-mail: msanches@net.ipen.br

2001-07-01

The transport of radioactive material has raised great interest on the part of national regulatory authorities, thus resulting in a safety measures improvement for all kinds of transportation. The transport of radioactive material is regulated by safety criteria much more than those applied to conventional hazardous material. All radioactive material transportation run in Brazilian territory must be in accordance with what is established by the CNEN-NE 5.01 - Transport of Radioactive Material. There are other national and international regulations for radioactive material transportation, which have to be accomplished with and adopted during the operation of radioactive material transportation. The aim of this paper is to verify the criteria set up in the existing regulations and propose a consensus for all the intervening organizations in the regulation process for land, air or sea transportation. This kind of transportation can not depend on the efforts of only one person, a group of workers or even any governmental body, but must be instead a shared responsibility among workers, transport firms and all regulative transportation organizations. (author)

A pH-dependent conformational ensemble mediates proton transport through the influenza A/M2 protein†

Science.gov (United States)

Polishchuk, Alexei L.; Lear, James D.; Ma, Chunlong; Lamb, Robert A.; Pinto, Lawrence H.; DeGrado, William F.

2010-01-01

The influenza A M2 protein exhibits inwardly rectifying, pH-activated proton transport that saturates at low pH. A comparison of high-resolution structures of the transmembrane domain at high and low pH suggests that pH-dependent conformational changes may facilitate proton conduction by alternately changing the accessibility of the N-terminal and C-terminal regions of the channel as a proton transits through the transmembrane domain. Here, we show that M2 functionally reconstituted in liposomes populates at least three different conformational states over a physiologically relevant pH range, with transition midpoints that are consistent with previously reported His37 pKas. We then develop and test two similar, quantitative mechanistic models of proton transport, where protonation shifts the equilibrium between structural states having different proton affinities and solvent accessibilities. The models account well for a collection of experimental data sets over a wide range of pHs and voltages and require only a small number of adjustable parameters to accurately describe the data. While the kinetic models do not require any specific conformation for the protein, they nevertheless are consistent with a large body of structural information based on high-resolution NMR and crystallographic structures, optical spectroscopy, and MD calculations. PMID:20968306

International Regulations for Transport of Radioactive Materials, History and Security

International Nuclear Information System (INIS)

EL-Shinawy, R.M.K.

2013-01-01

International Regulations for the transport of radioactive materials have been published by International Atomic Energy Agency (IAEA) since 1961. These Regulations have been widely adopted into national Regulations. Also adopted into different modal Regulations such as International Air Transport Association (IATA) and International Martime Organization (IMO). These Regulations provide standards for insuring a high level of safety of general public, transport workers, property and environment against radiation, contamination, criticality hazard and thermal effects associated with the transport of radioactive wastes and materials. Several reviews conducted in consultation with Member States (MS) and concerned international organizations, resulted in comprehensive revisions till now. Radioactive materials are generally transported by specialized transport companies and experts. Shippers and carriers have designed their transport operations to comply with these international Regulations. About 20 million consignments of radioactive materials take place around the world each year. These materials were used in different fields such as medicine, industry, agriculture, research, consumer product and electric power generation. After September 11,2001, the IAEA and MS have worked together to develop a new guidance document concerning the security in the transport of radioactive materials. IAEA have initiated activities to assist MS in addressing the need for transport security in a comprehensive manner. The security guidance and measures were mentioned and discussed. The transport security becomes more developed and integrated into national Regulations of many countries beside the safety Regulations. IAEA and other International organizations are working with MS to implement transport security programs such as guidance, training, security assessments and upgrade assistance in these fields.

Recent developments in the regulation of nuclear transportation

International Nuclear Information System (INIS)

Grella, A.W.

1978-01-01

In the past four years, almost all nations and international or intergovernmental transport organizations have effected transitions from the 1967 to 1973 IAEA standards as their basis for regulatory requirements for the safe transport of radioactive materials. One major exception to this transition is the USA itself, where this transition has not yet taken place. Major amendments to revise 49 CFR Parts 100-199 of the Department of Transportation regulations and 10 CFR Part 71 of the Nuclear Regulatory Commission regulations are required to effect this transition. The notices of proposed rulemaking to effect this transition in the USA are expected to be published by DOT and NRC concurrently sometime in 1978. Final amendments can be expected later, after the public comment period on the notices and considerations of those comments. This paper summarizes the status of current thinking on US adoption of the 1973 IAEA standards, as well as the status of adoption of those standards by international intergovernmental organizations, such as the Intergovernmental Maritime Consultative Organization, International Civil Aviation Organization, etc. A number of the differences between the expected US regulations and other regulations based on the 1973 IAEA standards are explained. This paper also discusses a number of other events or matters which have been taking place in the US in the past four years which have or may have an effect on transport of nuclear materials and its regulation, including air transport of plutonium, rail transport of spent fuel and other regulations by state or political subdivisions. The paper also discusses changes to US regulations accomplished in the past four years, which are not related to 1973 IAEA standards, as well as some other possible areas where regulatory proposals might be anticipated, such as control of radiation exposures to certain transport workers and other matters

Technical regulations for road transport of radioactive materials

International Nuclear Information System (INIS)

Juul-Jensen, P.; Ulbak, K.

1990-01-01

The technical regulations for the transport of radioactive materials in Denmark are set down by the (Danish) National Board of Health in collaboration with the (Danish) National Institute for Radiation Hygiene in accordance with paragraph 3 of the Danish Ministry of Justice's Executive Order no. 2 of 2, January 1985 on the national road transport of dangerous goods by road, as amended by exutive order no. 251 of April 29th 1987 and no. 704 of November 1989. These regulations are presented here. They are almost identical, with only very few exceptions indicated in the publication, with the rules for Class 7 of the European convention on international transport of dangerous goods by road (ADR). In addition to the aforementioned regulations for national road transport of radioactive materials the general rules for the transport of radioactive materials found in the National Board of Health's executive order no. 721 of November 27th 1989 on the transport of radioactive materials are valid. The abovementioned executive orders, with the exception of certain supplements which are not part of the technical regulations, are also contained in this publication. (AB)

Australian Experience in Implementing Transport Safety Regulations and Transport Security Recommendations

International Nuclear Information System (INIS)

Sarkar, S.

2016-01-01

Australian transport safety and security regulatory framework is governed by Commonwealth, State and Territory legislations. There are eleven competent authorities in Australia that includes three Commonwealth authorities, six states and two territory authorities. IAEA Regulations for Safe Transport of Radioactive Material (TS-R-1, 2005 edition) is applied through Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) Code of Practice for Transport of Radioactive Material 2008 by road, rail and waterways not covered by marine legislations. All states and territories apply this Transport Code through their regulatory system. For air transport, the Civil Aviation Act 1988 adopts the requirements of the ICAO Technical Instructions for the Safe Transport of Dangerous Goods by Air DOC 9284, which also adopts TS-R-1. The security of radioactive material in air transport is achieved via the Aviation Transport Security Act 2004. For sea transport Australian Marine Order 41 applies the requirements of IMDG (International Maritime Dangerous Goods) Code which also adopts TS-R-1. The security of radioactive material (nuclear material) is governed by two Commonwealth Agencies namely, ARPANSA and ASNO (Australian Safeguards and Non-proliferation Office) . ARPANSA regulates the security of radioactive sources through ARPANSA Code of Practice for the Security of Radioactive Sources 2007 which is based on the IAEA Draft Security Series. ASNO regulates security of nuclear material including U, Th and Pu through the Nuclear Non-Proliferation (Safeguards) Act, and the object of which is to give effect to certain obligations that Australia has as a party to the NPT, Australia’s safeguards agreement with the IAEA, and other bilateral safeguards agreements and certain obligations that Australia has as a party to the Convention for the Physical Protection of Nuclear Materials (CPPNM). This paper presents the effectiveness of regulatory approaches for safe and secure

The Murid Herpesvirus-4 gL regulates an entry-associated conformation change in gH.

Directory of Open Access Journals (Sweden)

Laurent Gillet

2008-07-01

Full Text Available The glycoprotein H (gH/gL heterodimer is crucial for herpesvirus membrane fusion. Yet how it functions is not well understood. The Murid Herpesvirus-4 gH, like that of other herpesviruses, adopts its normal virion conformation by associating with gL. However, gH switched back to a gL-independent conformation after virion endocytosis. This switch coincided with a conformation switch in gB and with capsid release. Virions lacking gL constitutively expressed the down-stream form of gH, prematurely switched gB to its down-stream form, and showed premature capsid release with poor infectivity. These data argue that gL plays a key role in regulating a gH and gB functional switch from cell binding to membrane fusion.

Management System for Regulating Transport of Radioactive Material

International Nuclear Information System (INIS)

Lopez Vietri, J.R.; Capadona, N.M.; Barenghi, L.G.

2011-01-01

The objective of this paper is to describe the main characteristics of the Nuclear Regulatory Authority (Autoridad Regulatoria Nuclear - ARN) management system applied to the transport of radioactive material, in Argentina. In the frame of ARN's quality policy, 'Protection against ionizing radiation on transport of radioactive materials' was selected as one of the regulatory processes, named TMR from now on. ARN's management system is integrally based on ISO 9000 system addressed to help organizations in designing and implementing their quality management systems. TMR process was split into five sub processes in order to facilitate the implementation of the system. Such sub processes were defined taking into account of the main functions developed by ARN in the branch of safe transport of radioactive materials. For each of this processes were specified their objectives, inputs, activities and outputs, clients and stakeholders, responsibilities, supporting documents, control of documents and records, control of non-conformances, monitoring and measurements, audits, feedback and improvement. Supporting documents for sub processes were issued, validated, reviewed and improved as an essential point to achieve continuous improving. Simultaneously, some indexes were defined to monitor and measures sub processes as a way to show objective evidence of conformity with objectives. Finally, as conclusions of this paper, they will be showed the main obstacles and troubleshooting found in the design and implementation of management system as well as their solutions and state of advance. (authors)

Conformational regulation of charge recombination reactions in a photosynthetic bacterial reaction center

DEFF Research Database (Denmark)

Katona, Gergely; Snijder, Arjan; Gourdon, Pontus Emanuel

2005-01-01

In bright light the photosynthetic reaction center (RC) of Rhodobacter sphaeroides stabilizes the P(+)(870).Q(-)(A) charge-separated state and thereby minimizes the potentially harmful effects of light saturation. Using X-ray diffraction we report a conformational change that occurs within the cy...... the cytoplasmic domain of this RC in response to prolonged illumination with bright light. Our observations suggest a novel structural mechanism for the regulation of electron transfer reactions in photosynthesis....

The properties of genome conformation and spatial gene interaction and regulation networks of normal and malignant human cell types.

Directory of Open Access Journals (Sweden)

Zheng Wang

Full Text Available The spatial conformation of a genome plays an important role in the long-range regulation of genome-wide gene expression and methylation, but has not been extensively studied due to lack of genome conformation data. The recently developed chromosome conformation capturing techniques such as the Hi-C method empowered by next generation sequencing can generate unbiased, large-scale, high-resolution chromosomal interaction (contact data, providing an unprecedented opportunity to investigate the spatial structure of a genome and its applications in gene regulation, genomics, epigenetics, and cell biology. In this work, we conducted a comprehensive, large-scale computational analysis of this new stream of genome conformation data generated for three different human leukemia cells or cell lines by the Hi-C technique. We developed and applied a set of bioinformatics methods to reliably generate spatial chromosomal contacts from high-throughput sequencing data and to effectively use them to study the properties of the genome structures in one-dimension (1D and two-dimension (2D. Our analysis demonstrates that Hi-C data can be effectively applied to study tissue-specific genome conformation, chromosome-chromosome interaction, chromosomal translocations, and spatial gene-gene interaction and regulation in a three-dimensional genome of primary tumor cells. Particularly, for the first time, we constructed genome-scale spatial gene-gene interaction network, transcription factor binding site (TFBS - TFBS interaction network, and TFBS-gene interaction network from chromosomal contact information. Remarkably, all these networks possess the properties of scale-free modular networks.

Conformational basis for the Li(+)-induced leak current in the rat gamma-aminobutyric acid (GABA) transporter-1

DEFF Research Database (Denmark)

MacAulay, Nanna; Zeuthen, Thomas; Gether, Ulrik

2002-01-01

The rat gamma-aminobutyric acid transporter-1 (GAT-1) was expressed in Xenopus laevis oocytes and the substrate-independent Li(+)-induced leak current was examined using two-electrode voltage clamp. The leak current was not affected by the addition of GABA and was not due to H(+) permeation. The Li......(+)-bound conformation of the protein displayed a lower passive water permeability than that of the Na(+)- and choline (Ch(+))-bound conformations and the leak current did not saturate with increasing amounts of Li(+) in the test solution. The mechanism that gives rise to the leak current did not support active water...... transport in contrast to the mechanism responsible for GABA translocation (approximately 330 water molecules per charge). Altogether, these data support the distinct nature of the leak conductance in relation to the substrate translocation process. It was observed that the leak current was inhibited by low...

Regulation of transport processes across the tonoplast membrane

Directory of Open Access Journals (Sweden)

Oliver eTrentmann

2014-09-01

Full Text Available In plants, the vacuole builds up the cellular turgor and represents an important component in cellular responses to diverse stress stimuli. Rapid volume changes of cells, particularly of motor cells, like guard cells, are caused by variation of osmolytes and consequently of the water contents in the vacuole. Moreover, directed solute uptake into or release out of the large central vacuole allows adaptation of cytosolic metabolite levels according to the current physiological requirements and specific cellular demands. Therefore, solute passage across the vacuolar membrane, the tonoplast, has to be tightly regulated. Important principles in vacuolar transport regulation are changes of tonoplast transport protein abundances by differential expression of genes or changes of their activities, e.g. due to post-translational modification or by interacting proteins. Because vacuolar transport is in most cases driven by an electro-chemical gradient altered activities of tonoplast proton pumps significantly influence vacuolar transport capacities. Intense studies on individual tonoplast proteins but also unbiased system biological approaches have provided important insights into the regulation of vacuolar transport. This short review refers to selected examples of tonoplast proteins and their regulation, with special focus on protein phosphorylation.

Regulation of organic anion transport in the liver

NARCIS (Netherlands)

Roelofsen, H; Jansen, PLM

1997-01-01

In several liver diseases the biliary transport is disturbed, resulting in, for example, jaundice and cholestasis. Many of these symptoms can be attributed to altered regulation of hepatic transporters. Organic anion transport, mediated by the canalicular multispecific organic anion transporter

Regulations relevant to the transport of radioactive materials in Switzerland

International Nuclear Information System (INIS)

Smith, L.

1996-01-01

As is the case in many countries, the transport of radioactive materials in Switzerland is primarily regulated by the national regulations for the transport of dangerous goods. Currently these regulations, in the case of radioactive material, incorporate the 1985 IAEA Safety Series 6 Regulations for the Safe Transport of Radioactive Material (As amended 1990). However, as is also the case in some other countries, consignors, shippers and carriers of radioactive materials must also comply with additional laws when shipping radioactive materials. The most important of these other laws and their accompanying regulations are those concerned with radiation protection (import, export and carriers licences) and nuclear power (import, export, inland transport and transit licences). This paper sets out to describe the collective requirements resulting from all three of these sets of regulations. (Author)

75 FR 49435 - Transportation Conformity Rule Restructuring Amendments

Science.gov (United States)

2010-08-13

... hours of operation, and special arrangements should be made for deliveries of boxed information... the need to update the rule each time a NAAQS is promulgated. The same hierarchy of conformity tests... hierarchy of regional conformity tests described below in B. of this section. Therefore, there is redundancy...

Regulations concerning marine transport and storage of dangerous things (abridged)

International Nuclear Information System (INIS)

1987-01-01

This report shows the Ordinances No.84 (1967) and No.30 (1957) of the Ministry of transport. The Ordinance No.84 has been published in detail elsewhere. The provisions concerning shipping transport and storage of dangerous substances deal with isolation of each dangerous substance, method for loading (cleaning of container, etc.), certificate for ship for transporting dangerous substances, renewal of certificate for ship for transporting dangerous substances, return of certificate, fee (for renewal and reissue of certificate), definition of terms, type of radioactive cargo (L-type cargo, A-type cargo, BM-type cargo, BU type cargo), transport of radioactive substances, type of fissionable cargo (Type I, Type II and Type III), confirmation of safety concerning radioactive cargo (conformity to standards, inspection, approval, etc.), limit of cargo volume, transport index, marking (type of cargo), confirmation of safety of transport, inspection of contamination, notice of transport, special measures, inspection of cargo (radioactive substances), requirements for container and package, etc. (Nogami, K.)

The accessibility in the external part of the TM5 of the glutamate transporter EAAT1 is conformationally sensitive during the transport cycle.

Directory of Open Access Journals (Sweden)

Xiuping Zhang

Full Text Available BACKGROUND: Excitatory amino acid transporter 1 (EAAT1 is a glutamate transporter which is a key element in the termination of the synaptic actions of glutamate. It serves to keep the extracellular glutamate concentration below neurotoxic level. However the functional significance and the change of accessibility of residues in transmembrane domain (TM 5 of the EAAT1 are not clear yet. METHODOLOGY/PRINCIPAL FINDINGS: We used cysteine mutagenesis with treatments with membrane-impermeable sulfhydryl reagent MTSET [(2-trimethylammonium methanethiosulfonate] to investigate the change of accessibility of TM5. Cysteine mutants were introduced from position 291 to 300 of the cysteine-less version of EAAT1. We checked the activity and kinetic parameters of the mutants before and after treatments with MTSET, furthermore we analyzed the effect of the substrate and blocker on the inhibition of the cysteine mutants by MTSET. Inhibition of transport by MTSET was observed in the mutants L296C, I297C and G299C, while the activity of K300C got higher after exposure to MTSET. V(max of L296C and G299C got lower while that of K300C got higher after treated by MTSET. The L296C, G299C, K300C single cysteine mutants showed a conformationally sensitive reactivity pattern. The sensitivity of L296C to MTSET was potentiated by glutamate and TBOA,but the sensitivity of G299C to MTSET was potentiated only by TBOA. CONCLUSIONS/SIGNIFICANCE: All these facts suggest that the accessibility of some positions of the external part of the TM5 is conformationally sensitive during the transport cycle. Our results indicate that some residues of TM5 take part in the transport pathway during the transport cycle.

Regulations for the safe transport of radioactive materials. 1973 rev. ed

International Nuclear Information System (INIS)

1973-01-01

The purpose of these Regulations is to establish standards of safety which provide an acceptable level of control of the radiation hazards to persons, property and the environment that are associated with the transport of radioactive material. These Regulations shall apply to the transport by land, water or air, including transport on own account, of radioactive material other than that which is an integral part of the means of transport. Transport shall be deemed to include any operation incidental to the whole course of carriage, such as loading, unloading and storage in transit. The term includes both normal transport and that under accident conditions. These Regulations do not apply within establishments where the radioactive material is produced, used or stored, other than in the course of transport, and in respect of which other appropriate safety regulations are in force. In the transport of radioactive materials, any other hazardous characteristics of these materials such as explosiveness, inflammability, pyrophoricity, chemical toxicity, and corrosiveness must be taken into account in such a manner as to be in compliance with the relevant transport regulations for dangerous goods of each of the countries through or into which the materials will be transported, as well as in compliance with these Regulations.

Regulation of Transportation of Radioactive Material in Indonesia

International Nuclear Information System (INIS)

Nirwono, Muttaqin Margo; Choi, Kwang Sik

2011-01-01

1.1. Background Indonesia is a biggest archipelago country with 17,508 islands in 33 provinces. In transportation Indonesia has large number of airports, railways, roadways, waterways, and merchant marines. Since nuclear and radiation utilizations are expanding on whole country, the mobilization of these is usually placed outside of controlled facilities, in the public domain, and often entails movement between countries. The Indonesian Nuclear Energy Regulatory Agency (BAPETEN) is responsible for supervision and also authorization of the transport of radioactive material (TRM). TRM is the specific movement of a radioactive material consignment from origin to destination by public transportation (road or rail, water and air). This study aims to determine whether national regulation is harmonized with international practice in ensuring safety and security of TRM. The finding of this study will provide recommendation for enhancement of regulation on TRM. 1.2. Regulation of TRM in Indonesia Government Regulation (GR) No. 26, 2002 on the Safe Transport of Radioactive Material is implemented pursuant to Act 10, 1997 on Nuclear Energy. This GR was repealed GR 13, 1975 on TRM. The GR 26 consist of 16 chapters and 39 articles, included licensing: authority and responsibilities: packaging: radiation protection programme; training: quality assurance programme: type and activity limit of radioactive materials: radioactive materials with other dangerous properties: emergency preparedness: administrative sanction: and penal provisions. Principally, this GR adopted IAEA-TS-R-1, 'Regulations for the Safe Transport of Radioactive Material', 1996's Edition

Role of bundle helices in a regulatory crosstalk in the trimeric betaine transporter BetP.

Science.gov (United States)

Gärtner, Rebecca M; Perez, Camilo; Koshy, Caroline; Ziegler, Christine

2011-12-02

The Na(+)-coupled betaine symporter BetP regulates transport activity in response to hyperosmotic stress only in its trimeric state, suggesting a regulatory crosstalk between individual protomers. BetP shares the overall fold of two inverted structurally related five-transmembrane (TM) helix repeats with the sequence-unrelated Na(+)-coupled symporters LeuT, vSGLT, and Mhp1, which are neither trimeric nor regulated in transport activity. Conformational changes characteristic for this transporter fold involve the two first helices of each repeat, which form a four-TM-helix bundle. Here, we identify two ionic networks in BetP located on both sides of the membrane that might be responsible for BetP's unique regulatory behavior by restricting the conformational flexibility of the four-TM-helix bundle. The cytoplasmic ionic interaction network links both first helices of each repeat in one protomer to the osmosensing C-terminal domain of the adjacent protomer. Moreover, the periplasmic ionic interaction network conformationally locks the four-TM-helix bundle between the same neighbor protomers. By a combination of site-directed mutagenesis, cross-linking, and betaine uptake measurements, we demonstrate how conformational changes in individual bundle helices are transduced to the entire bundle by specific inter-helical interactions. We suggest that one purpose of bundle networking is to assist crosstalk between protomers during transport regulation by specifically modulating the transition from outward-facing to inward-facing state. Copyright © 2011 Elsevier Ltd. All rights reserved.

14 CFR 1300.3 - Supplementary regulations of the Air Transportation Stabilization Board.

Science.gov (United States)

2010-01-01

... Transportation Stabilization Board. 1300.3 Section 1300.3 Aeronautics and Space AIR TRANSPORTATION SYSTEM... General § 1300.3 Supplementary regulations of the Air Transportation Stabilization Board. (a) The regulations in this part are supplemented by the regulations of the Air Transportation Stabilization Board in...

40 CFR 52.2133 - General conformity.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false General conformity. 52.2133 Section 52...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Carolina § 52.2133 General conformity. The General Conformity regulations adopted into the South Carolina State Implementation Plan which...

Transport coefficients in second-order non-conformal viscous hydrodynamics

International Nuclear Information System (INIS)

Ryblewski, Radoslaw

2015-01-01

Based on the exact solution of Boltzmann kinetic equation in the relaxation-time approximation, the precision of the two most recent formulations of relativistic second-order non-conformal viscous hydrodynamics (14-moment approximation and causal Chapman-Enskog method), standard Israel-Stewart theory, and anisotropic hydrodynamics framework, in the simple case of one-dimensional Bjorken expansion, is tested. It is demonstrated that the failure of Israel-Stewart theory in reproducing exact solutions of the Boltzmann kinetic equation occurs due to neglecting and/or choosing wrong forms of some of the second-order transport coefficients. In particular, the importance of shear-bulk couplings in the evolution equations for dissipative quantities is shown. One finds that, in the case of the bulk viscous pressure correction, such coupling terms are as important as the corresponding first-order Navier-Stokes term and must be included in order to obtain, at least qualitative, overall agreement with the kinetic theory. (paper)

New basic safety regulations of radioactive material transport in Russia

International Nuclear Information System (INIS)

Ananiev, V.V.; Ershov, V.N.; Shvedov, M.O.

2004-01-01

In the paper the system of normative regulation of radioactive material transport in Russia, basic principles and provisions of the new Russian regulations, available deviations from rules IAEA regulations are briefly considered. The problems, connected with putting in force of the new regulations in practice of transport, including problems of usage earlier designed and manufactured packages are considered as well

40 CFR 52.938 - General conformity.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false General conformity. 52.938 Section 52...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kentucky § 52.938 General conformity. The General Conformity regulations were submitted on November 10, 1995, and adopted into the Kentucky State...

Project-Level Conformity and Hot-Spot Analyses

Science.gov (United States)

This page contains policy guidance issued by EPA and/or the U.S. Department of Transportation to assist state and local transportation and air quality agencies implement the transportation conformity program.

New open conformation of SMYD3 implicates conformational selection and allostery

Directory of Open Access Journals (Sweden)

Nicholas Spellmon

2016-12-01

Full Text Available SMYD3 plays a key role in cancer cell viability, adhesion, migration and invasion. SMYD3 promotes formation of inducible regulatory T cells and is involved in reducing autoimmunity. However, the nearly “closed” substrate-binding site and poor in vitro H3K4 methyltransferase activity have obscured further understanding of this oncogenically related protein. Here we reveal that SMYD3 can adopt an “open” conformation using molecular dynamics simulation and small-angle X-ray scattering. This ligand-binding-capable open state is related to the crystal structure-like closed state by a striking clamshell-like inter-lobe dynamics. The two states are characterized by many distinct structural and dynamical differences and the conformational transition pathway is mediated by a reversible twisting motion of the C-terminal domain (CTD. The spontaneous transition from the closed to open states suggests two possible, mutually non-exclusive models for SMYD3 functional regulation and the conformational selection mechanism and allostery may regulate the catalytic or ligand binding competence of SMYD3. This study provides an immediate clue to the puzzling role of SMYD3 in epigenetic gene regulation.

Comparison between different regulations for transport of radioactive materials; Comparaison de differents reglements de transports des substances radioactives

Energy Technology Data Exchange (ETDEWEB)

Pallier, Lucien

1961-11-20

This comparison is based on the study of several regulations and conventions: French regulations for transports (by rail, road, river, sea, air, and mail), international regulations applicable in France for transports (by rail, road, air, sea, and mail), the general regulation for transport of the International Atomic Energy Agency, and the convention on civil responsibility of the European Agency for Nuclear Energy. The author notices that IAEA regulation will probably prevail. He outlines the objectives and the necessity of regulations, identifies the risk factors (nature of radio-elements, physical condition of the material, type of packaging), discusses additional safety measures, outlines that risks must not be overestimated, and the importance of labelling, and then discusses the comparison of the different considered regulations. He addresses the determination of the risk associated with a transport, the issue of responsibility. The content of regulations is presented in several tables.

Draft of regulations for road transport of radioactive wastes

International Nuclear Information System (INIS)

Gese, J.; Zizka, B.

1979-06-01

A draft regulation is presented for the transport of solid and solidified radioactive wastes from nuclear power plants. The draft takes into consideration dosimetric, safety and fire-fighting directives, transport organization, anticipated amounts of radioactive wastes, characteristics of containers, maintenance of vehicles, and equipment of vehicles and personnel. The draft is based on the provisional regulations governing the transport on public roads issued in 1973, valid directives, decrees, acts and standards, and complies with 1973 IAEA requirements. (J.P.)

Oregon Pupil Transportation Manual. Revised Regulations and Responsibilities.

Science.gov (United States)

Oregon State Dept. of Education, Salem.

Designed for use by Oregon school bus drivers and administrators, this manual answers common questions about school bus transportation in Oregon, including those about the laws governing pupil transportation, the regulations governing pupil transportation administration, and the laws on school bus operation. A chapter of advisory materials covers…

The application of dangerous goods regulations to the transport of radioactive wastes

International Nuclear Information System (INIS)

Blenkin, J.J.; Darby, W.P.; Heywood, J.D.; Wikinson, H.L.; Carrington, C.K.; Murray, M.A.

1998-01-01

Some radioactive materials to be transported, including certain radioactive wastes, contain materials that qualify as dangerous goods as defined by the United Nations Recommendations on the Transport of Dangerous Goods (United Nations 1997). The regulations governing the transport of radioactive and dangerous goods in the UK are largely based on the IAEA Regulations for the Safe Transport of Radioactive Material (IAEA 1990) and the UN Recommendations (United Nations 1993). Additional legislation will also apply including the Carriage of Dangerous Goods by Road (Driver Training) Regulations 1996 (UK 1996). The IAEA Transport Regulations are clear that where radioactive materials have other dangerous properties the requirements of other relevant transport regulations for dangerous goods must also be met. They require that consignments are appropriately segregated from other dangerous goods, in accordance with relevant legislation, and that dangerous properties such as explosiveness, flammability etc. are taken into account in packing, labelling, marking, placarding, storage and transport. In practice, however, it requires a clear understanding of the relationship between the IAEA Transport Regulations and other dangerous goods legislation in order to avoid a number of problems in the approval of package design. This paper discusses the regulations applying to the transport of dangerous goods and explores practical problems associated with implementing them. It highlights a number of opportunities for developing the regulations, to make them easier to apply to radioactive materials that also have other potentially dangerous properties. (authors)

Conformational dynamism for DNA interaction in the Salmonella RcsB response regulator.

Science.gov (United States)

Casino, Patricia; Miguel-Romero, Laura; Huesa, Juanjo; García, Pablo; García-Del Portillo, Francisco; Marina, Alberto

2018-01-09

The RcsCDB phosphorelay system controls an extremely large regulon in Enterobacteriaceae that involves processes such as biofilm formation, flagella production, synthesis of extracellular capsules and cell division. Therefore, fine-tuning of this system is essential for virulence in pathogenic microorganisms of this group. The final master effector of the RcsCDB system is the response regulator (RR) RcsB, which activates or represses multiple genes by binding to different promoter regions. This regulatory activity of RcsB can be done alone or in combination with additional transcriptional factors in phosphorylated or dephosphorylated states. The capacity of RcsB to interact with multiple promoters and partners, either dephosphorylated or phosphorylated, suggests an extremely conformational dynamism for this RR. To shed light on the activation mechanism of RcsB and its implication on promoter recognition, we solved the crystal structure of full-length RcsB from Salmonella enterica serovar Typhimurium in the presence and absence of a phosphomimetic molecule BeF3-. These two novel structures have guided an extensive site-directed mutagenesis study at the structural and functional level that confirms RcsB conformational plasticity and dynamism. Our data allowed us to propose a β5-T switch mechanism where phosphorylation is coupled to alternative DNA binding ways and which highlights the conformational dynamism of RcsB to be so pleiotropic. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

State statutes and regulations on radioactive materials transportation

International Nuclear Information System (INIS)

Foster, B.

1981-11-01

The transport of radioactive material is controlled by numerous legislative and regulatory actions at the federal, state, and local levels. This document is a compilation of the state level laws and regulations. The collected material is abstracted and indexed by states. Each state section contains three divisions: (1) abstracts of major statutes, (2) legislative rules, and (3) photocopies of relevant paragraphs from the law or regulation. This document was prepared for use by individuals who are involved in the radioactive material transportation process. This document will not be updated. The legislative rules section contains the name of the state agency primarily responsible for monitoring the transport of radioactive materials

Purification and crystallization of the cystic fibrosis transmembrane conductance regulator (CFTR).

Science.gov (United States)

Rosenberg, Mark F; Kamis, Alhaji Bukar; Aleksandrov, Luba A; Ford, Robert C; Riordan, John R

2004-09-10

The cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein that is mutated in patients suffering from cystic fibrosis. Here we report the purification and first crystallization of wild-type human CFTR. Functional characterization of the material showed it to be highly active. Electron crystallography of negatively stained two-dimensional crystals of CFTR has revealed the overall architecture of this channel for two different conformational states. These show a strong structural homology to two conformational states of another eukaryotic ATP-binding cassette transporter, P-glycoprotein. In contrast to P-glycoprotein, however, both conformational states can be observed in the presence of a nucleotide, which may be related to the role of CFTR as an ion channel rather than a transporter. The hypothesis that the two conformations could represent the "open" and "closed" states of the channel is considered.

Regulation on the transport of nuclear fuel materials by vehicles

International Nuclear Information System (INIS)

1984-01-01

The regulations applying to the transport of nuclear fuel materials by vehicles, mentioned in the law for the regulations of nuclear source materials, nuclear fuel materials and reactors. The transport is for outside of the factories and the site of enterprises by such modes of transport as rail, trucks, etc. Covered are the following: definitions of terms, places of fuel materials handling, loading methods, limitations on mix loading with other cargo, radiation dose rates concerning the containers and the vehicles, transport indexes, signs and indications, limitations on train linkage during transport by rail, security guards, transport of empty containers, etc. together with ordinary rail cargo and so on. (Mori, K.)

Investment in transport infrastructure, regulation, and gas-gas competition

Energy Technology Data Exchange (ETDEWEB)

Gasmi, Farid [Toulouse School of Economics (ARQADE and IDEI), Universite Toulouse 1 Capitole (France); Oviedo, Juan Daniel [Universidad del Rosario (Colombia)

2010-05-15

This paper develops a simple model in which a regulated (upstream) transporter provides capacity to a marketer competing in output with an incumbent in the (downstream) gas commodity market. The equilibrium outcome of the firms' interaction in the downstream market is explicitly taken into account by the regulator when setting the transport charge. We consider various forms of competition in this market and derive the corresponding optimal transport charge policies. We then run simulations that allow us to perform a comparative welfare analysis of these transport infrastructure investment policies based on different assumptions about the intensity of the competition that prevails in the gas commodity market. (author)

Investment in transport infrastructure, regulation, and gas-gas competition

International Nuclear Information System (INIS)

Gasmi, Farid; Oviedo, Juan Daniel

2010-01-01

This paper develops a simple model in which a regulated (upstream) transporter provides capacity to a marketer competing in output with an incumbent in the (downstream) gas commodity market. The equilibrium outcome of the firms' interaction in the downstream market is explicitly taken into account by the regulator when setting the transport charge. We consider various forms of competition in this market and derive the corresponding optimal transport charge policies. We then run simulations that allow us to perform a comparative welfare analysis of these transport infrastructure investment policies based on different assumptions about the intensity of the competition that prevails in the gas commodity market. (author)

The amended regulations for the safe transport of radioactive materials in Japan

International Nuclear Information System (INIS)

Takemura, Yoshio

1978-01-01

To cope with the inadequacies of the laws and regulations including the Law Concerning Prevention of Radiation Injuries Due to Radioisotopes, Etc., the Amended Regulations for the Safe Transport of Radioactive Materials in Japan has been issued. It is based on the Regulations of IAEA for the Safe Transport of Radioactive Materials and the Technical Standards for the Transport of Radioactive Materials decided by the AEC of Japan. In the amended regulations, emphasis is placed on the safety design of transporting goods. They are classified in Types L, A and B according to shock resistance and fire resistance, and the quantities of radioisotopes allowed to be contained in respective types are specified. The following matters are described: basic ideas concerning the types of transporting goods, test standards for the goods, transport standards for the goods, and nondestructive test apparatuses in transport. (Mori, K.)

National RAM transport regulations implementation in Russia

International Nuclear Information System (INIS)

Gubanov, V.A.

1995-01-01

A brief review is given of the main provisions of the state regulation and safety assurance of RAM transport in Russia. This appears to be useful to various persons and organisations abroad, concerned with such transport in Russia. Two aspects of the system are presented - regulatory documents (normative-technical documentation) and regulatory and control activities of state organisations. (Author)

Insights into the post-transcriptional regulation of the mitochondrial electron transport chain.

Science.gov (United States)

Sirey, Tamara M; Ponting, Chris P

2016-10-15

The regulation of the mitochondrial electron transport chain is central to the control of cellular homeostasis. There are significant gaps in our understanding of how the expression of the mitochondrial and nuclear genome-encoded components of the electron transport chain are co-ordinated, and how the assembly of the protein complexes that constitute the electron transport chain are regulated. Furthermore, the role post-transcriptional gene regulation may play in modulating these processes needs to be clarified. This review summarizes the current knowledge regarding the post-transcriptional gene regulation of the electron transport chain and highlights how noncoding RNAs may contribute significantly both to complex electron transport chain regulatory networks and to mitochondrial dysfunction. © 2016 The Author(s).

Present situation and influence of new ICRP recommendations on radioactive material transport regulations

International Nuclear Information System (INIS)

Hamard, J.; Ringot, C.

1991-01-01

The publication of new ICRP recommendations will involve the revision of IAEA standards and consequently the revision of transport regulations for radioactive materials. Transport regulations are briefly reviewed and application for radiation protection of workers and public is examined. Influence of new recommendations on transport regulations and eventual modifications on classification and transport of materials, packaging design and permissible exposure for workers and public in the prospect of regulation revision forecasted for 1995

76 FR 70220 - New Jersey Regulations on Transportation of Regulated Medical Waste

Science.gov (United States)

2011-11-10

...., Director, Healthcare Waste Institute, 4301 Connecticut Avenue NW., Suite 300, Washington, DC 20008, and (2... Hazardous Waste Management Program, Mail Code 401-02C, P.O. Box 420, Trenton, NJ 08625-0420. A certification.... PHMSA-2011-0294 (PDA-35(R)] New Jersey Regulations on Transportation of Regulated Medical Waste AGENCY...

Conformational regulation of urokinase receptor function

DEFF Research Database (Denmark)

Gårdsvoll, Henrik; Jacobsen, Benedikte; Kriegbaum, Mette C

2011-01-01

PA per se into the hydrophobic ligand binding cavity of uPAR that modulates the function of this receptor. Based on these data, we now propose a model in which the inherent interdomain mobility in uPAR plays a major role in modulating its function. Particularly one uPAR conformation, which is stabilized...

75 FR 51392 - Federal Management Regulation; Transportation Management

Science.gov (United States)

2010-08-20

...; Docket Number 2010-0011, sequence 1] RIN 3090-AJ03 Federal Management Regulation; Transportation Management AGENCY: Office of Governmentwide Policy, General Services Administration (GSA). ACTION: Final rule. SUMMARY: The General Services Administration (GSA) is amending the Federal Management Regulation (FMR) by...

Regulations concerning marine transport and storage of dangerous things (abridged)

International Nuclear Information System (INIS)

1981-01-01

When the dangerous things of different classes or items are loaded on a same ship, they shall be separated mutually according to the specified standards. Containers shall be cleaned well before loading dangerous things. When there is the danger of heating, gasification, corrosion and other critical physical or chemical processes by the mutual action of the dangerous things of different items or dangerous things and other goods, they must not be loaded in a same container. Basic terms are defined, such as radioactive transported goods, fissile transported goods and exclusive loading. Radioactive transported goods are classified into types of L, A, BM and BU, and fissile transported goods into 3 kinds. Each type of these goods is defined in size and radioactivity. When the makers of radioactive transported goods pack radioactive materials into the transported goods of type BM or BU, they shall get before shipment the confirmation of the Minister of Transport concerning the standard to which these goods conform. The maximum radiation dose rate must not exceed 200 milli-rem an hour on the surface and 10 milli-rem an hour at the distance of 1 meter from the surfaces of containers loaded with radioactive transported goods. Signs, the limit of shipment and other related matters are prescribed in detail. (Okada, K.)

Regulations concerning marine transport and storage of dangerous things (abridged)

International Nuclear Information System (INIS)

1985-01-01

When the dangerous things of different classes or items are loaded on a same ship, they shall be separated mutually according to the specified standards. Containers shall be cleaned well before loading dangerous things. When there is the danger of heating, gasification, corrosion and other critical physical or chemical processes by the mutual action of the dangerous things of different items or dangerous things and other goods, they must not be loaded in a same container. Basic terms are defined, such as radioactive transported goods, fissile transported goods and exclusive loading. Radioactive transported goods are classified into types of L, A, BM and BU, and fissile transported goods into 3 kinds. Each type of these goods is defined in size and radioactivity. When the makers of radioactive transported goods pack radioactive materials into the transported goods of type BM or BU, they shall get before shipment the confirmation of the Minister of Transport concerning the standard to which these goods conform. The maximum radiation dose rate must not exceed 200 milli-rem an hour on the surface and 10 milli-rem an hour at the distance of 1 meter from the surfaces of containers loaded with radioactive transported goods. Signs, the limit of shipment and other related matters are prescribed in detail. (Kubozono, M.)

N-MYC DOWN-REGULATED-LIKE Proteins Regulate Meristem Initiation by Modulating Auxin Transport and MAX2 Expression

OpenAIRE

Mudgil, Yashwanti; Ghawana, Sanjay; Jones, Alan M.

2013-01-01

Background N-MYC DOWN-REGULATED-LIKE (NDL) proteins interact with the G? subunit (AGB1) of the heterotrimeric G protein complex and play an important role in AGB1-dependent regulation of lateral root formation by affecting root auxin transport, auxin gradients and the steady-state levels of mRNA encoding the PIN-FORMED 2 and AUXIN 1 auxin transport facilitators. Auxin transport in aerial tissue follows different paths and utilizes different transporters than in roots; therefore, in the presen...

The alternating access mechanism of transport as observed in the sodium-hydantoin transporter Mhp1

International Nuclear Information System (INIS)

Weyand, Simone; Shimamura, Tatsuro; Beckstein, Oliver; Sansom, Mark S. P.; Iwata, So; Henderson, Peter J. F.; Cameron, Alexander D.

2011-01-01

Crystal structures of a membrane protein transporter in three different conformational states provide insights into the transport mechanism. Secondary active transporters move molecules across cell membranes by coupling this process to the energetically favourable downhill movement of ions or protons along an electrochemical gradient. They function by the alternating access model of transport in which, through conformational changes, the substrate binding site alternately faces either side of the membrane. Owing to the difficulties in obtaining the crystal structure of a single transporter in different conformational states, relatively little structural information is known to explain how this process occurs. Here, the structure of the sodium-benzylhydantoin transporter, Mhp1, from Microbacterium liquefaciens, has been determined in three conformational states; from this a mechanism is proposed for switching from the outward-facing open conformation through an occluded structure to the inward-facing open state

Activation of ion transport systems during cell volume regulation

International Nuclear Information System (INIS)

Eveloff, J.L.; Warnock, D.G.

1987-01-01

This review discusses the activation of transport pathways during volume regulation, including their characteristics, the possible biochemical pathways that may mediate the activation of transport pathways, and the relations between volume regulation and transepithelial transport in renal cells. Many cells regulate their volume when exposed to an anisotonic medium. The changes in cell volume are caused by activation of ion transport pathways, plus the accompanying osmotically driven water movement such that cell volume returns toward normal levels. The swelling of hypertonically shrunken cells is termed regulatory volume increase (RVI) and involves an influx of NaCl into the cell via either activation of Na-Cl, Na-K-2Cl cotransport systems, or Na + -H + and Cl - -HCO 3 - exchangers. The reshrinking of hypotonically swollen cells is termed regulatory volume decrease (RVD) and involves an efflux of KCl and water from the cell by activation of either separate K + and Cl - conductances, a K-Cl cotransport system, or parallel K + -H + and Cl - -HCO 3 - exchangers. The biochemical mechanisms involved in the activation of transport systems are largely unknown, however, the phosphoinositide pathway may be implicated in RVI; phorbol esters, cGMP, and Ca 2+ affect the process of volume regulation. Renal tubular cells, as well as the blood cells that transverse the medulla, are subjected to increasing osmotic gradients from the corticomedullary junction to the papillary tip, as well as changing interstitial and tubule fluid osmolarity, depending on the diuretic state of the animal. Medullary cells from the loop of Henle and the papilla can volume regulate by activating Na-K-2Cl cotransport or Na + -H + and Cl - -HCO 3 - exchange systems

Regulations for the Safe Transport of Radioactive Materials. Vietnam Standard (TCVN 4985-89)

International Nuclear Information System (INIS)

1989-01-01

The regulations were prepared in line with the Safety Regulation for Ionizing Radiations 1988 of Vietnam. Its purpose is to provide requirements in transport of radioactive materials. The exposure levels of transport personnel are determined. The package for different types of materials is regulated. The orders and procedures in transport are defined. In addition, specific requirements for each mean of transport are given. (N.H.A)

Structure of a eukaryotic CLC transporter defines an intermediate state in the transport cycle

Science.gov (United States)

Feng, Liang; Campbell, Ernest B.; Hsiung, Yichun; MacKinnon, Roderick

2011-01-01

CLC proteins transport Cl− ions across cell membranes to control the electrical potential of muscle cells, transfer electrolytes across epithelia, and control the pH and electrolyte composition of intracellular organelles. Some members of this protein family are Cl− ion channels, while others are secondary active transporters that exchange Cl− ions and H+ with a 2:1 stoichiometry. We have determined the structure of a eukaryotic CLC transporter at 3.5 Å resolution. Cytoplasmic CBS domains are strategically positioned to regulate the ion transport pathway, and many disease-causing mutations in human CLCs reside on the CBS-transmembrane interface. Comparison with prokaryotic CLC shows that a gating glutamate changes conformation and suggests a basis for 2:1 Cl−/H+ exchange and a simple mechanistic connection between CLC channels and transporters. PMID:20929736

Transport of radioactive material in Sudan practice and regulations

International Nuclear Information System (INIS)

Abdalla, M. K. E.

2010-12-01

In the last couple of decades there has been an impressive increase in applications of radioactive material. Such an extensive and widely spread usage of radioactive materials demands safe transportation of radioactive material from the production site to the application location, as well as quick and effective response in a case of an unexpected transportation event according to Sudan Atomic Energy Commission (SAEC) regulation. The thesis described the local practice for transport of radioactive material as compared to the international standards for radiation protection, and also discussed the emergency procedures that must be follow in case of accident during transport of radioactive material. Furthermore, the objective of this study was also to set proposals for how to cope in the event of a radiological accident. The study methods included survey of current literature on safe transport of radioactive material, survey of national regulations on the subjects in additional to case studies aimed at investigating the practical issues pertinent to transport of radioactive materials in Sudan. A comprehensive review was presented on how to classification of radioactive packages and general requirement for all packaging and packages according to international standard. transport of number of radioactive sources from Khartoum airport to the field was evaluated with regard transport index, category of source, type of package, dose rate around the source, time to destination and means of transport of doses to public, worker are be made. All results were within the limit specified in the national as well as international regulation. The study has addressed for the first time the practice of transport of radioactive material in Sudan. It is anticipated that the results will encourage national organizational and professional bodies to enhance radiation protection and safety of radioactive sources. (Author)

Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption

Science.gov (United States)

Patel, Chirag; Douard, Veronique; Yu, Shiyan; Gao, Nan; Ferraris, Ronaldo P.

2015-01-01

Dietary fructose that is linked to metabolic abnormalities can up-regulate its own absorption, but the underlying regulatory mechanisms are not known. We hypothesized that glucose transporter (GLUT) protein, member 5 (GLUT5) is the primary fructose transporter and that fructose absorption via GLUT5, metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein-in-brain 11 (Rab11)a-dependent endosomes are each required for regulation. Introducing fructose but not lysine and glucose solutions into the lumen increased by 2- to 10-fold the heterogeneous nuclear RNA, mRNA, protein, and activity levels of GLUT5 in adult wild-type mice consuming chow. Levels of GLUT5 were >100-fold that of candidate apical fructose transporters GLUTs 7, 8, and 12 whose expression, and that of GLUT 2 and the sodium-dependent glucose transporter protein 1 (SGLT1), was not regulated by luminal fructose. GLUT5-knockout (KO) mice exhibited no facilitative fructose transport and no compensatory increases in activity and expression of SGLT1 and other GLUTs. Fructose could not up-regulate GLUT5 in GLUT5-KO, KHK-KO, and intestinal epithelial cell-specific Rab11a-KO mice. The fructose-specific metabolite glyceraldehyde did not increase GLUT5 expression. GLUT5 is the primary transporter responsible for facilitative absorption of fructose, and its regulation specifically requires fructose uptake and metabolism and normal GLUT5 trafficking to the apical membrane.—Patel, C., Douard, V., Yu, S., Gao, N., Ferraris, R. P. Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption. PMID:26071406

Regulations for the safe transport of radioactive material. 1996 edition (revised)

International Nuclear Information System (INIS)

2000-01-01

Following a comprehensive review by panels of experts convened by the IAEA starting in 1991, a revised version of the IAEA Regulations for the Safe Transport of Radioactive Material (formerly Safety Series No. 6) was approved by the Board of Governors in September 1996. This publication supersedes all editions of the Regulations issued under Safety Series No. 6. By 1969, the Regulations had been adopted by almost all international organizations concerned with transport and used by many Member States for their own regulations. Through the worldwide adoption of the IAEA Regulations for all modes of transport, a very high standard of safety in transport has been achieved. In the revisions since the first edition, attempts have been made to find a balance between the need to take account of technical advances and operational experience, and the desirability of providing a stable framework of regulatory requirements. One of the aims of this approach is to allow packages designed to previous versions of the Regulations to continue to be used for a reasonable period of time. It is recognized that not all regulatory changes can be implemented simultaneously; Member States and international organizations are therefore invited, in adopting this revision, to provide for use of both the 'old' requirements and the 'new' ones during a period of transition that may last for a few years. It is further recommended that adoption of these revised Regulations occur within a period of five years from publication to achieve worldwide harmonization of their application. In implementing the provisions of these Regulations, it may be necessary for Member States to issue complementary national regulations. Except as necessary for solely domestic purposes, such national regulations should not conflict with these Regulations. For convenience, the requirements to be met for the transport of specified types of consignments are included in an abbreviated form as Schedules in this publication

Regulations for the safe transport of radioactive material. 1996 edition (revised)

International Nuclear Information System (INIS)

2002-01-01

Following a comprehensive review by panels of experts convened by the IAEA starting in 1991, a revised version of the IAEA Regulations for the Safe Transport of Radioactive Material (formerly Safety Series No. 6) was approved by the Board of Governors in September 1996. This publication supersedes all editions of the Regulations issued under Safety Series No. 6. By 1969, the Regulations had been adopted by almost all international organizations concerned with transport and used by many Member States for their own regulations. Through the worldwide adoption of the IAEA Regulations for all modes of transport, a very high standard of safety in transport has been achieved. In the revisions since the first edition, attempts have been made to find a balance between the need to take account of technical advances and operational experience, and the desirability of providing a stable framework of regulatory requirements. One of the aims of this approach is to allow packages designed to previous versions of the Regulations to continue to be used for a reasonable period of time. It is recognized that not all regulatory changes can be implemented simultaneously. Member States and international organizations are therefore invited, in adopting this revision, to provide for use of both the 'old' requirements and the 'new' ones during a period of transition that may last for a few years. It is further recommended that adoption of these revised Regulations occur within a period of five years from publication to achieve worldwide harmonization of their application. In implementing the provisions of these Regulations, it may be necessary for Member States to issue complementary national regulations. Except as necessary for solely domestic purposes, such national regulations should not conflict with these Regulations. For convenience, the requirements to be met for the transport of specified types of consignments are included in an abbreviated form as Schedules in this publication

Potential impacts of ICRP 60 and 61 on transportation

International Nuclear Information System (INIS)

Rawl, R.R.

1992-01-01

The International Commission on Radiological Protection (ICRP) has issued its ''1990 Recommendations of the International Commission on Radiation Protection'' that provide guidance on controlling exposure to ionizing radiation (1). The ICRP recommendations and their incorporation into the International Atomic Energy Agency's (IAEA) ''Basic Safety Standards,'' Safety Series No. 9, provide the basis on which the IAEA ''Regulation for the Safe Transport of Radioactive Materials,'' Safety Series No. 6, are built. The transportation regulations are developed to ensure safety during the movement of radioactive materials and to provide reasonable assurance the transportation activities comply with the basic radiation protection principles of Safety Series No. 9. During the 1985 revision of the IAEA transport regulations, a comprehensive model was developed to derive Type A (non-accident resistant) package contents limits that were consistent with Safety Series No.9 and, consequently, the earlier ICRP recommendations (2). Now that ICRP 60 has been published, the IAEA and Member States are faced with the task of evaluating how the transport regulations need to be revised to conform with the new recommendations. Several potentially significant issues need to be addressed to determine whether the old linkages between the recommendations and the transport regulations require modification. This paper addresses the issues that arise from the revisions to the ICRP recommendations and how the transportation regulations may be affected

Potential impacts of ICRP 60 and 61 on transportation

International Nuclear Information System (INIS)

Rawl, Richard R.

1992-01-01

The International Commission on Radiological Protection (IGRP) has issued its '1990 Recommendations of the International Commission on Radiation Protection' that provide guidance on controlling exposure to ionizing radiation. The ICRP recommendations and their incorporation into the International Atomic Energy Agency's (IAEA) 'Basic Safety Standards', Safety Series No. 9, provide the basis on which the IAEA 'Regulations for the Safe Transport of Radioactive Materials', Safety Series No. 6, are built. The transportation regulations are developed to ensure safety during the movement of radioactive materials and to provide reasonable assurance the transportation activities comply with the basic radiation protection principles of Safety Series No. 9. During the 1985 revision of the IAEA transport regulations, a comprehensive model was developed to derive Type A (non-accident resistant) package contents limits that were consistent with Safety Series No. 9 and, consequently, the earlier ICRP recommendations. Now that ICRP 60 has been published, the IAEA and Member States are faced with the task of evaluating how the transport regulations need to be revised to conform with the new recommendations. Several potentially significant issues need to be addressed to determine whether the old linkages between the recommendations and the transport regulations require modification. This paper addresses the issues that arise from the revisions to the ICRP recommendations and how the transportation regulations may be affected. (author)

Extracellular creatine regulates creatine transport in rat and human muscle cells.

OpenAIRE

Loike, J D; Zalutsky, D L; Kaback, E; Miranda, A F; Silverstein, S C

1988-01-01

Muscle cells do not synthesize creatine; they take up exogenous creatine by specific Na+-dependent plasma membrane transporters. We found that extracellular creatine regulates the level of expression of these creatine transporters in L6 rat muscle cells. L6 myoblasts maintained for 24 hr in medium containing 1 mM creatine exhibited 1/3rd of the creatine transport activity of cells maintained for 24 hr in medium without creatine. Down-regulation of creatine transport was partially reversed whe...

N-MYC down-regulated-like proteins regulate meristem initiation by modulating auxin transport and MAX2 expression.

Science.gov (United States)

Mudgil, Yashwanti; Ghawana, Sanjay; Jones, Alan M

2013-01-01

N-MYC down-regulated-like (NDL) proteins interact with the Gβ subunit (AGB1) of the heterotrimeric G protein complex and play an important role in AGB1-dependent regulation of lateral root formation by affecting root auxin transport, auxin gradients and the steady-state levels of mRNA encoding the PIN-FORMED 2 and AUXIN 1 auxin transport facilitators. Auxin transport in aerial tissue follows different paths and utilizes different transporters than in roots; therefore, in the present study, we analyzed whether NDL proteins play an important role in AGB1-dependent, auxin-mediated meristem development. Expression levels of NDL gene family members need to be tightly regulated, and altered expression (both over-expression and down-regulation) confers ectopic growth. Over-expression of NDL1 disrupts vegetative and reproductive organ development. Reduced expression of the NDL gene family members results in asymmetric leaf emergence, twinning of rosette leaves, defects in leaf formation, and abnormal silique distribution. Reduced expression of the NDL genes in the agb1-2 (null allele) mutant rescues some of the abnormal phenotypes, such as silique morphology, silique distribution, and peduncle angle, suggesting that proper levels of NDL proteins are maintained by AGB1. We found that all of these abnormal aerial phenotypes due to altered NDL expression were associated with increases in basipetal auxin transport, altered auxin maxima and altered MAX2 expression within the inflorescence stem. NDL proteins, together with AGB1, act as positive regulators of meristem initiation and branching. AGB1 and NDL1 positively regulate basipetal inflorescence auxin transport and modulate MAX2 expression in shoots, which in turn regulates organ and lateral meristem formation by the establishment and maintenance of auxin gradients.

N-MYC down-regulated-like proteins regulate meristem initiation by modulating auxin transport and MAX2 expression.

Directory of Open Access Journals (Sweden)

Yashwanti Mudgil

Full Text Available N-MYC down-regulated-like (NDL proteins interact with the Gβ subunit (AGB1 of the heterotrimeric G protein complex and play an important role in AGB1-dependent regulation of lateral root formation by affecting root auxin transport, auxin gradients and the steady-state levels of mRNA encoding the PIN-FORMED 2 and AUXIN 1 auxin transport facilitators. Auxin transport in aerial tissue follows different paths and utilizes different transporters than in roots; therefore, in the present study, we analyzed whether NDL proteins play an important role in AGB1-dependent, auxin-mediated meristem development.Expression levels of NDL gene family members need to be tightly regulated, and altered expression (both over-expression and down-regulation confers ectopic growth. Over-expression of NDL1 disrupts vegetative and reproductive organ development. Reduced expression of the NDL gene family members results in asymmetric leaf emergence, twinning of rosette leaves, defects in leaf formation, and abnormal silique distribution. Reduced expression of the NDL genes in the agb1-2 (null allele mutant rescues some of the abnormal phenotypes, such as silique morphology, silique distribution, and peduncle angle, suggesting that proper levels of NDL proteins are maintained by AGB1. We found that all of these abnormal aerial phenotypes due to altered NDL expression were associated with increases in basipetal auxin transport, altered auxin maxima and altered MAX2 expression within the inflorescence stem.NDL proteins, together with AGB1, act as positive regulators of meristem initiation and branching. AGB1 and NDL1 positively regulate basipetal inflorescence auxin transport and modulate MAX2 expression in shoots, which in turn regulates organ and lateral meristem formation by the establishment and maintenance of auxin gradients.

Rab proteins: The key regulators of intracellular vesicle transport

International Nuclear Information System (INIS)

Bhuin, Tanmay; Roy, Jagat Kumar

2014-01-01

Vesicular/membrane trafficking essentially regulates the compartmentalization and abundance of proteins within the cells and contributes in many signalling pathways. This membrane transport in eukaryotic cells is a complex process regulated by a large and diverse array of proteins. A large group of monomeric small GTPases; the Rabs are essential components of this membrane trafficking route. Most of the Rabs are ubiquitously expressed proteins and have been implicated in vesicle formation, vesicle motility/delivery along cytoskeleton elements and docking/fusion at target membranes through the recruitment of effectors. Functional impairments of Rabs affecting transport pathways manifest different diseases. Rab functions are accompanied by cyclical activation and inactivation of GTP-bound and GDP-bound forms between the cytosol and membranes which is regulated by upstream regulators. Rab proteins are characterized by their distinct sub-cellular localization and regulate a wide variety of endocytic, transcytic and exocytic transport pathways. Mutations of Rabs affect cell growth, motility and other biological processes. - Highlights: • Rab proteins regulate different signalling pathways. • Deregulation of Rabs is the fundamental causes of a variety of human diseases. • This paper gives potential directions in developing therapeutic targets. • This paper also gives ample directions for modulating pathways central to normal physiology. • These are the huge challenges for drug discovery and delivery in near future

Rab proteins: The key regulators of intracellular vesicle transport

Energy Technology Data Exchange (ETDEWEB)

Bhuin, Tanmay [Cell and Developmental Biology Unit, Department of Zoology, The University of Burdwan, Golapbag 713104 (India); Roy, Jagat Kumar, E-mail: jkroy@bhu.ac.in [Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221005 (India)

2014-10-15

Vesicular/membrane trafficking essentially regulates the compartmentalization and abundance of proteins within the cells and contributes in many signalling pathways. This membrane transport in eukaryotic cells is a complex process regulated by a large and diverse array of proteins. A large group of monomeric small GTPases; the Rabs are essential components of this membrane trafficking route. Most of the Rabs are ubiquitously expressed proteins and have been implicated in vesicle formation, vesicle motility/delivery along cytoskeleton elements and docking/fusion at target membranes through the recruitment of effectors. Functional impairments of Rabs affecting transport pathways manifest different diseases. Rab functions are accompanied by cyclical activation and inactivation of GTP-bound and GDP-bound forms between the cytosol and membranes which is regulated by upstream regulators. Rab proteins are characterized by their distinct sub-cellular localization and regulate a wide variety of endocytic, transcytic and exocytic transport pathways. Mutations of Rabs affect cell growth, motility and other biological processes. - Highlights: • Rab proteins regulate different signalling pathways. • Deregulation of Rabs is the fundamental causes of a variety of human diseases. • This paper gives potential directions in developing therapeutic targets. • This paper also gives ample directions for modulating pathways central to normal physiology. • These are the huge challenges for drug discovery and delivery in near future.

Radioactive materials and nuclear fuel transport requirements in Poland in the light of international regulations

International Nuclear Information System (INIS)

Musialowicz, T.

1977-01-01

National regulations for the transport of radioactive materials and nuclear fuel in Poland are discussed. Basic transport requirements and regulations, transport experience including transport accidents and emergency service are described. The comparison with international regulations is given

National Automated Conformity Inspection Process -

Data.gov (United States)

Department of Transportation — The National Automated Conformity Inspection Process (NACIP) Application is intended to expedite the workflow process as it pertains to the FAA Form 81 0-10 Request...

Production, regulation and transportation of bacillibactin in bacillus subtilis

International Nuclear Information System (INIS)

Raza, W.; Hussain, Q.; Shen, Q.

2012-01-01

Bacillus subtilis produces a catecholate type siderophore 'Bacillibactin'. This review focuses on the non-ribosomal synthesis, transport and regulation of bacillibactin. Bacillibactin biosynthetic operon contains five genes (dhbACEBF). The uptake of bacillibactin requires the FeuABC transporter, inner-membrane permease, FepDG and YusV ATPase and an esterase encoding gene, besA and while export required YmfE major facilitator super-family (MFS)-type transporter. Fur is the major iron-controlled transcriptional regulator in B. subtilis, which acts as an iron-dependent repressor of the dhb operon in vivo while an iron-independent repressor in vitro. Knowledge of the Fur regulon will be useful in interpreting other global analysis of transcriptional responses. (author)

Regulations for the safe transport of radioactive material. 1996 ed.

International Nuclear Information System (INIS)

1996-01-01

This publication is the revised version of the IAEA's Regulations for the Safe Transport of Radioactive Materials as approved by the Board of Governors in September 1996. It establishes standards of safety which provide an acceptable level of control of the radiation, criticality and thermal hazards to persons, property and the environment that are associated with the transport of radioactive material. After an introductory section, the publication is structured as follows: Section 2 defines the terms that are required for the purposes of the Regulations; Section 3 provides general provisions; Section 4 gives the activity limits and material restrictions used throughout these Regulations; Section 5 provides requirements and controls for transport; Section 6 provides requirements for radioactive materials and for packagings and packages; Section 7 provides requirements for test procedures; Section 8 provides approval and administrative requirements. The requirements for the transport of specified types of consignments are included in an abbreviated form as Schedules. Refs, figs, tabs

The Structure of a Sugar Transporter of the Glucose EIIC Superfamily Provides Insight into the Elevator Mechanism of Membrane Transport.

Science.gov (United States)

McCoy, Jason G; Ren, Zhenning; Stanevich, Vitali; Lee, Jumin; Mitra, Sharmistha; Levin, Elena J; Poget, Sebastien; Quick, Matthias; Im, Wonpil; Zhou, Ming

2016-06-07

The phosphoenolpyruvate:carbohydrate phosphotransferase systems are found in bacteria, where they play central roles in sugar uptake and regulation of cellular uptake processes. Little is known about how the membrane-embedded components (EIICs) selectively mediate the passage of carbohydrates across the membrane. Here we report the functional characterization and 2.55-Å resolution structure of a maltose transporter, bcMalT, belonging to the glucose superfamily of EIIC transporters. bcMalT crystallized in an outward-facing occluded conformation, in contrast to the structure of another glucose superfamily EIIC, bcChbC, which crystallized in an inward-facing occluded conformation. The structures differ in the position of a structurally conserved substrate-binding domain that is suggested to play a central role in sugar transport. In addition, molecular dynamics simulations suggest a potential pathway for substrate entry from the periplasm into the bcMalT substrate-binding site. These results provide a mechanistic framework for understanding substrate recognition and translocation for the glucose superfamily EIIC transporters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structure of a Eukaryotic CLC Transporter Defines an Intermediate State in the Transport Cycle

International Nuclear Information System (INIS)

Feng, Liang; Campbell, Ernest B.; Hsiung, Yichun; MacKinnon, Roderick

2010-01-01

CLC proteins transport chloride (Cl - ) ions across cell membranes to control the electrical potential of muscle cells, transfer electrolytes across epithelia, and control the pH and electrolyte composition of intracellular organelles. Some members of this protein family are Cl - ion channels, whereas others are secondary active transporters that exchange Cl - ions and protons (H + ) with a 2:1 stoichiometry. We have determined the structure of a eukaryotic CLC transporter at 3.5 angstrom resolution. Cytoplasmic cystathionine beta-synthase (CBS) domains are strategically positioned to regulate the ion-transport pathway, and many disease-causing mutations in human CLCs reside on the CBS-transmembrane interface. Comparison with prokaryotic CLC shows that a gating glutamate residue changes conformation and suggests a basis for 2:1 Cl - /H + exchange and a simple mechanistic connection between CLC channels and transporters.

Role IAEA implementation of ICRP-60 on regulations the safe transport of radioactive material

International Nuclear Information System (INIS)

Elshinawy, R.K.M.; Gomaa, M.A.

1994-01-01

In november 1990, the (ICRP) adopted its 1990 recommendations (ICRP-60) ( 1). These recommendations will significantly influence not only IAEA's basic safety standards (safety series 9) ( 2), but also the IAEA regulations for the safe transport of radioactive material ( 3) and its supporting documents ( 4-6). IAEA experts are currently engaged in the revision of the transport regulations. This revision process led to the publication of the revised transport regulations of 1966. The transport regulations are developed to ensure safety during movement of radioactive materials, and to provide reasonable assurance that the transport activities comply with the basic safety standards for radiation protection

Evidence for distinct sodium-, dopamine-, and cocaine-dependent conformational changes in transmembrane segments 7 and 8 of the dopamine transporter

DEFF Research Database (Denmark)

Norregaard, Lene; Loland, Claus Juul; Gether, Ulrik

2003-01-01

. Inhibitors such as cocaine did not alter the effect of MTSET in M371C. The protection of M371C inactivation by dopamine required Na+. Because dopamine binding is believed to be Na+-independent, this suggests that dopamine induces a transport-associated conformational change that decreases the reactivity of M......371C with MTSET. In contrast to M371C, cocaine decreased the reaction rate of A399C with MTSET, whereas dopamine had no effect. The protection by cocaine can either reflect that Ala-399 lines the cocaine binding crevice or that cocaine induces a conformational change that decreases the reactivity of A...

The regulation concerning transportation of radioactive materials by vehicles

International Nuclear Information System (INIS)

1978-01-01

The Regulation is established on the basis of The law for the regulations of nuclear source materials, nuclear fuel materials and reactors'' and the ''Law for the prevention of radiation injuries due to radioisotopes.'' The prescriptions cover the transport of radioactive materials by railway, street rail way, ropeway, trolley buses, motorcars and light vehicles. Terms are explained, such as nuclear fuel materials, radioisotopes, radioactive substances, transported radioactive things, transported fissile things, vehicles, containers, exclusive loading, surrounding inspection area. Four types of transported radioactive things are specified, L and A types being less dangerous and BM and BU being more dangerous. Transported fissile things are classified to three kinds according to the safety to criticality of such things. Transported radioactive things except those of L type and containers with transported fissile things shall not be loaded or unloaded at the places where persons other than those concerned come in usually. Loading and unloading of such things shall be carried out so that the safety of such things is not injured. The maximum dose rate of radiation of the containers with transported radioactive things shall not be more than 200 millirem per hour on the surface and 10 millirem per hour at the distance of 1 meter. Specified transported radioactive things shall be particularly marked by the letter of ''radioactive'' or other signs indicating as such. (Okada, K.)

Second-order hydrodynamics and universality in non-conformal holographic fluids

International Nuclear Information System (INIS)

Kleinert, Philipp; Probst, Jonas

2016-01-01

We study second-order hydrodynamic transport in strongly coupled non-conformal field theories with holographic gravity duals in asymptotically anti-de Sitter space. We first derive new Kubo formulae for five second-order transport coefficients in non-conformal fluids in (3+1) dimensions. We then apply them to holographic RG flows induced by scalar operators of dimension Δ=3. For general background solutions of the dual bulk geometry, we find explicit expressions for the five transport coefficients at infinite coupling and show that a specific combination, H̃=2ητ π −2(κ−κ ∗ )−λ 2 , always vanishes. We prove analytically that the Haack-Yarom identity H=2ητ π −4λ 1 −λ 2 =0, which is known to be true for conformal holographic fluids at infinite coupling, also holds when taking into account leading non-conformal corrections. The numerical results we obtain for two specific families of RG flows suggest that H vanishes regardless of conformal symmetry. Our work provides further evidence that the Haack-Yarom identity H=0 may be universally satisfied by strongly coupled fluids.

Second-order hydrodynamics and universality in non-conformal holographic fluids

Energy Technology Data Exchange (ETDEWEB)

Kleinert, Philipp; Probst, Jonas [Rudolf Peierls Centre for Theoretical Physics, University of Oxford, 1 Keble Road, Oxford OX1 3NP (United Kingdom)

2016-12-19

We study second-order hydrodynamic transport in strongly coupled non-conformal field theories with holographic gravity duals in asymptotically anti-de Sitter space. We first derive new Kubo formulae for five second-order transport coefficients in non-conformal fluids in (3+1) dimensions. We then apply them to holographic RG flows induced by scalar operators of dimension Δ=3. For general background solutions of the dual bulk geometry, we find explicit expressions for the five transport coefficients at infinite coupling and show that a specific combination, H̃=2ητ{sub π}−2(κ−κ{sup ∗})−λ{sub 2}, always vanishes. We prove analytically that the Haack-Yarom identity H=2ητ{sub π}−4λ{sub 1}−λ{sub 2}=0, which is known to be true for conformal holographic fluids at infinite coupling, also holds when taking into account leading non-conformal corrections. The numerical results we obtain for two specific families of RG flows suggest that H vanishes regardless of conformal symmetry. Our work provides further evidence that the Haack-Yarom identity H=0 may be universally satisfied by strongly coupled fluids.

Actin retrograde flow controls natural killer cell response by regulating the conformation state of SHP-1.

Science.gov (United States)

Matalon, Omri; Ben-Shmuel, Aviad; Kivelevitz, Jessica; Sabag, Batel; Fried, Sophia; Joseph, Noah; Noy, Elad; Biber, Guy; Barda-Saad, Mira

2018-03-01

Natural killer (NK) cells are a powerful weapon against viral infections and tumor growth. Although the actin-myosin (actomyosin) cytoskeleton is crucial for a variety of cellular processes, the role of mechanotransduction, the conversion of actomyosin mechanical forces into signaling cascades, was never explored in NK cells. Here, we demonstrate that actomyosin retrograde flow (ARF) controls the immune response of primary human NK cells through a novel interaction between β-actin and the SH2-domain-containing protein tyrosine phosphatase-1 (SHP-1), converting its conformation state, and thereby regulating NK cell cytotoxicity. Our results identify ARF as a master regulator of the NK cell immune response. Since actin dynamics occur in multiple cellular processes, this mechanism might also regulate the activity of SHP-1 in additional cellular systems. © 2018 The Authors.

Regulation and roles of bicarbonate transport in cancer

Directory of Open Access Journals (Sweden)

Andrej eGorbatenko

2014-04-01

Full Text Available A unifying feature of solid tumors is a markedly altered pH profile compared to normal tissues. This reflects that solid tumors, despite completely different origins, often share several phenotypic properties with implications for intra- and extracellular pH. These include: a metabolic shift in most cancer cells towards more acid-producing pathways, reflecting both oncogenic signaling and the development of hypoxia in poorly perfused regions of the tumors; the poorly perfused and often highly dense tumor microenvironment, reducing the diffusive flux of acid equivalents compared to that in normal tissues; and the markedly altered regulation of the expression and activity of pH-regulatory transport proteins in the cancer cells. While some of these properties of tumors have been well described in recent years, the great majority of the research in this clinically important area has focused on proton transport, in particular via the Na+/H+-exchanger 1 (SLC9A1, NHE1 and various H+ ATPases. We have, however, recently demonstrated that at least under some conditions, including in vitro models of HER2 positive breast cancer, and measurements obtained directly in freshly dissected human mammary tumors, bicarbonate transporters such as the electroneutral Na+,HCO3--cotransporter (SLC4A7, NBCn1, are upregulated and play central roles in pH regulation. In this review, we summarize and discuss the current knowledge regarding the regulation and roles of bicarbonate transport in cancer.

Recommendations on the transport of dangerous goods. Model regulations. 11. revised ed.

International Nuclear Information System (INIS)

1999-01-01

The Recommendations on the Transport of Dangerous Goods are addressed to governments and to the international organizations concerned with the regulation of the transport of dangerous goods. They have been prepared by the United Nations Economic and Social Council's Committee of Experts on the Transport of Dangerous Goods, and they were first published in 1956 (ST/ECA/43-E/CN.2/170). Pursuant to Resolution 645 G (XXIII) of 26 April 1957 of the Economic and Social Council and subsequent resolutions, they have been regularly amended and updated at succeeding sessions of the Committee of Experts. At its eighteenth session (28 November-7 December 1994), the Committee of Experts considered that reformatting the Recommendations on the Transport of Dangerous Goods into Model Regulations that could be directly integrated into all modal national and international regulations would enhance harmonization, facilitate regular up-dating of all legal instruments concerned, and result in overall considerable resource savings for the Governments of the Member States, the United Nations, the specialized agencies and other international organizations. At its nineteenth session (2-10 December 1996), the Committee adopted a first version of the Model Regulations on the Transport of Dangerous Goods, which was annexed to the tenth revised edition of the Recommendations on the Transport of Dangerous Goods. At its twentieth session (7-16 December 1998), the Committee adopted various amendments to the Model Regulations and new provisions including, in particular, packing instructions for individual substances and articles and additional provisions for the transport of radioactive material. The additional provisions concerning the transport of radioactive material were developed in close cooperation with the International Atomic Energy Agency (IAEA) and are based on the 1996 Edition of the IAEA Regulations for the Safe Transport of Radioactive Material which have been reformatted so as to be

14 CFR 221.61 - Rules and regulations governing foreign air transportation.

Science.gov (United States)

2010-01-01

... governing foreign air transportation. Instead of being included in the fares tariffs, the rules and regulations governing foreign air transportation required to be filed by §§ 221.20 and 221.30 and/or... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Rules and regulations governing foreign air...

Greater-than-Class C low-level radioactive waste transportation regulations and requirements study

International Nuclear Information System (INIS)

Tyacke, M.; Schmitt, R.

1993-07-01

The purpose of this report is to identify the regulations and requirements for transporting greater-than-Class C (GTCC) low-level radioactive waste (LLW) and to identify planning activities that need to be accomplished in preparation for transporting GTCC LLW. The regulations and requirements for transporting hazardous materials, of which GTCC LLW is included, are complex and include several Federal agencies, state and local governments, and Indian tribes. This report is divided into five sections and three appendices. Section 1 introduces the report. Section 2 identifies and discusses the transportation regulations and requirements. The regulations and requirements are divided into Federal, state, local government, and Indian tribes subsections. This report does not identify the regulations or requirements of specific state, local government, and Indian tribes, since the storage, treatment, and disposal facility locations and transportation routes have not been specifically identified. Section 3 identifies the planning needed to ensure that all transportation activities are in compliance with the regulations and requirements. It is divided into (a) transportation packaging; (b) transportation operations; (c) system safety and risk analysis, (d) route selection; (e) emergency preparedness and response; and (f) safeguards and security. This section does not provide actual planning since the details of the Department of Energy (DOE) GTCC LLW Program have not been finalized, e.g., waste characterization and quantity, storage, treatment and disposal facility locations, and acceptance criteria. Sections 4 and 5 provide conclusions and referenced documents, respectively

Stretch-stimulated glucose transport in skeletal muscle is regulated by Rac1.

Science.gov (United States)

Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian; Richter, Erik A; Jensen, Thomas E

2015-02-01

Rac1 regulates stretch-stimulated (i.e. mechanical stress) glucose transport in muscle. Actin depolymerization decreases stretch-induced glucose transport in skeletal muscle. Rac1 is a required part of the mechanical stress-component of the contraction-stimulus to glucose transport in skeletal muscle. An alternative to the canonical insulin signalling pathway for glucose transport is muscle contraction/exercise. Mechanical stress is an integrated part of the muscle contraction/relaxation cycle, and passive stretch stimulates muscle glucose transport. However, the signalling mechanism regulating stretch-stimulated glucose transport is not well understood. We recently reported that the actin cytoskeleton regulating GTPase, Rac1, was activated in mouse muscle in response to stretching. Rac1 is a regulator of contraction- and insulin-stimulated glucose transport, however, its role in stretch-stimulated glucose transport and signalling is unknown. We therefore investigated whether stretch-induced glucose transport in skeletal muscle required Rac1 and the actin cytoskeleton. We used muscle-specific inducible Rac1 knockout mice as well as pharmacological inhibitors of Rac1 and the actin cytoskeleton in isolated soleus and extensor digitorum longus muscles. In addition, the role of Rac1 in contraction-stimulated glucose transport during conditions without mechanical load on the muscles was evaluated in loosely hanging muscles and muscles in which cross-bridge formation was blocked by the myosin ATPase inhibitors BTS and Blebbistatin. Knockout as well as pharmacological inhibition of Rac1 reduced stretch-stimulated glucose transport by 30-50% in soleus and extensor digitorum longus muscle. The actin depolymerizing agent latrunculin B similarly decreased glucose transport in response to stretching by 40-50%. Rac1 inhibition reduced contraction-stimulated glucose transport by 30-40% in tension developing muscle but did not affect contraction-stimulated glucose transport in

Regulation of transport in the connecting tubule and cortical collecting duct

Science.gov (United States)

Staruschenko, Alexander

2012-01-01

The central goal of this overview article is to summarize recent findings in renal epithelial transport, focusing chiefly on the connecting tubule (CNT) and the cortical collecting duct (CCD). Mammalian CCD and CNT are involved in fine tuning of electrolyte and fluid balance through reabsorption and secretion. Specific transporters and channels mediate vectorial movements of water and solutes in these segments. Although only a small percent of the glomerular filtrate reaches the CNT and CCD, these segments are critical for water and electrolyte homeostasis since several hormones, e.g. aldosterone and arginine vasopressin, exert their main effects in these nephron sites. Importantly, hormones regulate the function of the entire nephron and kidney by affecting channels and transporters in the CNT and CCD. Knowledge about the physiological and pathophysiological regulation of transport in the CNT and CCD and particular roles of specific channels/transporters has increased tremendously over the last two decades. Recent studies shed new light on several key questions concerning the regulation of renal transport. Precise distribution patterns of transport proteins in the CCD and CNT will be reviewed, and their physiological roles and mechanisms mediating ion transport in these segments will be also covered. Special emphasis will be given to pathophysiological conditions appearing as a result of abnormalities in renal transport in the CNT and CCD. PMID:23227301

Frequent down-regulation of ABC transporter genes in prostate cancer

International Nuclear Information System (INIS)

Demidenko, Rita; Razanauskas, Deividas; Daniunaite, Kristina; Lazutka, Juozas Rimantas; Jankevicius, Feliksas; Jarmalaite, Sonata

2015-01-01

ATP-binding cassette (ABC) transporters are transmembrane proteins responsible for the efflux of a wide variety of substrates, including steroid metabolites, through the cellular membranes. For better characterization of the role of ABC transporters in prostate cancer (PCa) development, the profile of ABC transporter gene expression was analyzed in PCa and noncancerous prostate tissues (NPT). TaqMan Low Density Array (TLDA) human ABC transporter plates were used for the gene expression profiling in 10 PCa and 6 NPT specimens. ABCB1 transcript level was evaluated in a larger set of PCa cases (N = 78) and NPT (N = 15) by real-time PCR, the same PCa cases were assessed for the gene promoter hypermethylation by methylation-specific PCR. Expression of eight ABC transporter genes (ABCA8, ABCB1, ABCC6, ABCC9, ABCC10, ABCD2, ABCG2, and ABCG4) was significantly down-regulated in PCa as compared to NPT, and only two genes (ABCC4 and ABCG1) were up-regulated. Down-regulation of ABC transporter genes was prevalent in the TMPRSS2-ERG-negative cases. A detailed analysis of ABCB1 expression confirmed TLDA results: a reduced level of the transcript was identified in PCa in comparison to NPT (p = 0.048). Moreover, the TMPRSS2-ERG-negative PCa cases showed significantly lower expression of ABCB1 in comparison to NPT (p = 0.003) or the fusion-positive tumors (p = 0.002). Promoter methylation of ABCB1 predominantly occurred in PCa and was rarely detected in NPT (p < 0.001). The study suggests frequent down-regulation of the ABC transporter genes in PCa, especially in the TMPRSS2-ERG-negative tumors. The online version of this article (doi:10.1186/s12885-015-1689-8) contains supplementary material, which is available to authorized users

Conformational Rigidity and Protein Dynamics at Distinct Timescales Regulate PTP1B Activity and Allostery.

Science.gov (United States)

Choy, Meng S; Li, Yang; Machado, Luciana E S F; Kunze, Micha B A; Connors, Christopher R; Wei, Xingyu; Lindorff-Larsen, Kresten; Page, Rebecca; Peti, Wolfgang

2017-02-16

Protein function originates from a cooperation of structural rigidity, dynamics at different timescales, and allostery. However, how these three pillars of protein function are integrated is still only poorly understood. Here we show how these pillars are connected in Protein Tyrosine Phosphatase 1B (PTP1B), a drug target for diabetes and cancer that catalyzes the dephosphorylation of numerous substrates in essential signaling pathways. By combining new experimental and computational data on WT-PTP1B and ≥10 PTP1B variants in multiple states, we discovered a fundamental and evolutionarily conserved CH/π switch that is critical for positioning the catalytically important WPD loop. Furthermore, our data show that PTP1B uses conformational and dynamic allostery to regulate its activity. This shows that both conformational rigidity and dynamics are essential for controlling protein activity. This connection between rigidity and dynamics at different timescales is likely a hallmark of all enzyme function. Copyright © 2017 Elsevier Inc. All rights reserved.

Conformational Regulation of the Essential Epigenetic Regulator UHRF1

KAUST Repository

Pantoja Angles, Aaron

2018-05-01

UHRF1 is an essential epigenetic regulator implicated in the maintenance of DNA methylation. While its functional state has been suggested to be allosterically regulated by phosphatidylinositol 5-phosphate and dependent on purification conditions and tags coupled to the protein, the expression system might have a broader impact on UHRF1s interaction properties. We hypothesized that the translation kinetics defined by the expression host has an impact on the folding process of the protein, which ultimately affects its structure and function. To test this idea, the cDNA of UHRF1 was recoded in order to generate optimized and harmonized sequences that were expected to alter the overall translation speed. Both proteins were expressed in Escherichia coli BL21-DE3 and their interaction profiles with H3K9me3 and unmodified H3 peptides were determined by microscale thermophoresis assays. The dissociation constants were compared by ttests in order to evaluate a possible change in the interaction properties of the optimized and harmonized proteins, compared to non-optimized UHRF1 expressed in E. coli BL21-DE3. While no difference was found for the interaction of optimized UHRF1 with the H3K9me3 peptide, a significant difference was found for its interaction with the unmodified H3 peptide. Moreover, both the interactions of harmonized UHRF1 with H3K9me3 and unmodified H3 peptides were determined to change. For this reason, we concluded that translation kinetics dependent on the expression system impacts the functional state of UHRF1. To further study this phenomenon, we expressed the consensus sequence of UHRF1 in Escherichia coli BL21-Codon Plus-(DE3)-RIL, a bacterial strain that is enriched with arginine, isoleucine, and leucine tRNA isoacceptors. Differences in its interaction profile with histone peptides were found when compared with UHRF1 expressed in Escherichia coli BL21-DE3. Since the major difference between these strains is the abundance of tRNAs, we obtained

Conformity Adequacy Review: Region 5

Science.gov (United States)

Resources are for air quality and transportation government and community leaders. Information on the conformity SIP adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 5 (IL, IN, MI, OH, WI) is provided here.

Spatiotemporal Regulation of Nuclear Transport Machinery and Microtubule Organization

Science.gov (United States)

Okada, Naoyuki; Sato, Masamitsu

2015-01-01

Spindle microtubules capture and segregate chromosomes and, therefore, their assembly is an essential event in mitosis. To carry out their mission, many key players for microtubule formation need to be strictly orchestrated. Particularly, proteins that assemble the spindle need to be translocated at appropriate sites during mitosis. A small GTPase (hydrolase enzyme of guanosine triphosphate), Ran, controls this translocation. Ran plays many roles in many cellular events: nucleocytoplasmic shuttling through the nuclear envelope, assembly of the mitotic spindle, and reorganization of the nuclear envelope at the mitotic exit. Although these events are seemingly distinct, recent studies demonstrate that the mechanisms underlying these phenomena are substantially the same as explained by molecular interplay of the master regulator Ran, the transport factor importin, and its cargo proteins. Our review focuses on how the transport machinery regulates mitotic progression of cells. We summarize translocation mechanisms governed by Ran and its regulatory proteins, and particularly focus on Ran-GTP targets in fission yeast that promote spindle formation. We also discuss the coordination of the spatial and temporal regulation of proteins from the viewpoint of transport machinery. We propose that the transport machinery is an essential key that couples the spatial and temporal events in cells. PMID:26308057

The safe control of the transport of radioactive material in France

International Nuclear Information System (INIS)

Chaumette, L.

2000-01-01

The regulation of the transport of radioactive and fissile material for civil use concerns the protection of human beings and the environment against the radiological risk which can occur by these conveyed material. That's why this regulation particularly calls upon the law of the protection of the environment, upon the law of the transport of dangerous goods and upon the nuclear law. According to the International Atomic Energy Agency [I.A.E.A.], the implementation of this regulation gives the transport a high level of safety. It comes from I.A.E.A's recommendations which have taken into account lessons from the scientific research and from technical experiences. These recommendations are implemented in international binding modal regulations so that they can be adapted to the ways of transport. Their acceptance in the inner law goes with some national specific laws, mainly connected with the operator's missions and responsibilities. So this technical and administrative regulation is rather complex, and its codification would make it clearer. Nevertheless the whole regulation meets the double aim of the law in transport of dangerous goods which is to insure the safety of this transport of dangerous goods without prejudicing exchanges. In order to apply the regulation, the operators use supervision procedure to check their activities are in conformity with the law. In addition to these procedures, the Authorities supervise this conformity from time to time, by making boring. Operators and the Authorities involve their responsibility which is dependent either on the system of civil responsibility in case of damage, or on the system of administrative responsibility in case of error or risk, or on the system of penal responsibility in case of infraction of the law. So the operators have to apply the regulation and the Administration has to enforce this regulation they have built up. However, the self-control of the safety of the transport of radioactive

Natural gas transport, regulation in UK

International Nuclear Information System (INIS)

Goldoni, Giovanni

2005-01-01

The detailed analysis contained in this case history demonstrates the great efforts made in the field of incentive regulation in order to promote competition in the gas market and to improve the efficiency of the gas transport system. The next challenge will be to preserve competition and efficiency in a quite different gas-supply condition [it

Analysis of an ATP-induced conformational transition of ABC transporter MsbA using a coarse-grained model.

Science.gov (United States)

Arai, Naoki; Furuta, Tadaomi; Sakurai, Minoru

2017-01-01

Upon the binding of ATP molecules to nucleotide binding domains (NBDs), ATP-binding cassette (ABC) exporters undergo a conformational transition from an inward-facing (IF) to an outward-facing (OF) state. This molecular event is a typical example of chemo-mechanical coupling. However, the underlying mechanism remains unclear. In this study, we analyzed the IF→OF transition of a representative ABC exporter, MsbA, by solving the equation of motion under an elastic network model (ENM). ATP was represented as a single node in ENM or replaced by external forces. When two ATP nodes were added to the ENM of the IF state protein, the two NBDs dimerized; subsequently, the two transmembrane domains opened toward the extracellular side, resulting in the formation of the OF structure. Such a conformational transition was also reproduced by applying external forces, which caused the rotational motion of the NBDs instead of the addition of ATP nodes. The process of the conformational transition was analyzed in detail using cross-correlation maps for node-node interactions. More importantly, it was revealed that the ATP binding energy is converted into distortion energy of several transmembrane helices. These results are useful for understanding the chemo-mechanical coupling in ABC transporters.

40 CFR 86.407-78 - Certificate of conformity required.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Certificate of conformity required. 86... Regulations for 1978 and Later New Motorcycles, General Provisions § 86.407-78 Certificate of conformity... conformity issued pursuant to this subpart, except as specified in paragraph (b) of this section, or...

Study of polymer molecules and conformations with a nanopore

Science.gov (United States)

Golovchenko, Jene A.; Li, Jiali; Stein, Derek; Gershow, Marc H.

2010-12-07

The invention features methods for evaluating the conformation of a polymer, for example, for determining the conformational distribution of a plurality of polymers and to detect binding or denaturation events. The methods employ a nanopore which the polymer, e.g., a nucleic acid, traverses. As the polymer traverses the nanopore, measurements of transport properties of the nanopore yield data on the conformation of the polymer.

Neurofilament subunit (NFL) head domain phosphorylation regulates axonal transport of neurofilaments.

LENUS (Irish Health Repository)

Yates, Darran M

2009-04-01

Neurofilaments are the intermediate filaments of neurons and are synthesised in neuronal cell bodies and then transported through axons. Neurofilament light chain (NFL) is a principal component of neurofilaments, and phosphorylation of NFL head domain is believed to regulate the assembly of neurofilaments. However, the role that NFL phosphorylation has on transport of neurofilaments is poorly understood. To address this issue, we monitored axonal transport of phosphorylation mutants of NFL. We mutated four known phosphorylation sites in NFL head domain to either preclude phosphorylation, or mimic permanent phosphorylation. Mutation to preclude phosphorylation had no effect on transport but mutation of three sites to mimic permanent phosphorylation inhibited transport. Mutation of all four sites together to mimic permanent phosphorylation proved especially potent at inhibiting transport and also disrupted neurofilament assembly. Our results suggest that NFL head domain phosphorylation is a regulator of neurofilament axonal transport.

Regulations of safe transport of radioactive material

International Nuclear Information System (INIS)

Patel, R.J.; Sumathi, E.

2017-01-01

BARC is a multi-disciplinary nuclear research organisation with facilities located at various parts of the country. The nuclear and radiological facilities in BARC include fuel fabrication facilities, nuclear research reactors, radiological laboratories, nuclear recycle facilities, waste management facilities and other associated facilities. RAdioactive Material (RAM) such as fresh nuclear fuel, irradiated fuel, radioactive sources, vitrified high level wastes, special nuclear material etc., are transported between these facilities either within the controlled premises or in public domain. In BARC the regulatory approval for the packages used for transport of RAM is issued by BARC Safety Council (BSC). Competent Authority for issuing the design approval for the BARC packages in public domain is Director, BARC. In this aspect BSC is assisted by Safety Review Committee-Transport of Radioactive Material (SRC-TRM) constituted by BSC entrusted with the mandate to ensure the packages are designed, manufactured and transported in accordance with the current regulations. This article summarizes the regulatory requirements for transport of RAM and experience in BARC facilities

Safe Transport of Radioactive Material, International Regulations and its Supporting Documents

International Nuclear Information System (INIS)

El-Shinawy, R.M.K.

2005-01-01

Safe transport of radioactive material regulations issued by IAEA since 1961, provide standards for insuring a high level of safety of people,transport workers, property and environment against radiation, contamination and criticality hazards as well as thermal effects associated with the transport of the radioactive wastes and material. The history ,development, philosophy and scope of these international regulations were mentioned as well as the different supporting documents to the regulations for safe transport of radioactive material were identified.The first supporting document , namely TS - G-1.1 ( ST-2) ,Advisory material is also issued by the IAEA.It contains both the advisory and explanatory materials previously published in safety series No 7 and 37 and therefore TS-G-1.1 (ST-2) will supersede safety series No 7 and 37. The second supporting document namely TS-G-1.2 (ST-3), planning and preparing for emergency response to transport accidents involving radioactive material ,which will supersede safety series No 87. In addition to quality assurance (SS=113), compliance assurance (SS=112), the training manual and other

Safe Transport of Radioactive Material, International Regulations and its Supporting Documents

Energy Technology Data Exchange (ETDEWEB)

El-Shinawy, R M.K. [Radiation Protection Dept., NRC, Atomic Energy Authority, Cairo (Egypt)

2005-04-01

Safe transport of radioactive material regulations issued by IAEA since 1961, provide standards for insuring a high level of safety of people,transport workers, property and environment against radiation, contamination and criticality hazards as well as thermal effects associated with the transport of the radioactive wastes and material. The history ,development, philosophy and scope of these international regulations were mentioned as well as the different supporting documents to the regulations for safe transport of radioactive material were identified.The first supporting document , namely TS - G-1.1 ( ST-2) ,Advisory material is also issued by the IAEA.It contains both the advisory and explanatory materials previously published in safety series No 7 and 37 and therefore TS-G-1.1 (ST-2) will supersede safety series No 7 and 37. The second supporting document namely TS-G-1.2 (ST-3), planning and preparing for emergency response to transport accidents involving radioactive material ,which will supersede safety series No 87. In addition to quality assurance (SS=113), compliance assurance (SS=112), the training manual and other.

Compendium of federal and state radioactive materials transportation laws and regulations: Transportation Legislative Database (TLDB)

International Nuclear Information System (INIS)

1989-10-01

The Transportation Legislative Database (TLDB) is an on-line information service containing detailed information on legislation and regulations regarding the transportation of radioactive materials in the United States. The system is dedicated to serving the legislative and regulatory information needs of the US Department of Energy and other federal agencies; state, tribal, and local governments; the hazardous materials transportation industry; and interested members of the general public. In addition to the on-line information service, quarterly and annual Legal Developments Reports are produced using information from the TLDB. These reports summarize important changes in federal and state legislation, regulations, administrative agency rulings, and judicial decisions over the reporting period. Information on significant legal developments at the tribal and local levels is also included on an as-available basis. Battelle's Office of Transportation Systems and Planning (OTSP) will also perform customized searches of the TLDB and produce formatted printouts in response to specific information requests

The Swedish sea transportation system for safety reasons

International Nuclear Information System (INIS)

Dybeck, P.

1993-01-01

Sweden began to design and build a sea transportation system. The ship M/S SIGYN is specially designed for transports of radioactive waste. It is a combined roll-on/roll-off and lift-on/lift-off vessel. It is built for world wide operation and with the highest requirements of two independent classification societies, Lloyds Register of Shipping and Bureau Veritas. The ship is also designed to conform to the Swedish/Finish ice class 1A. The transport cask for spent fuel, TN 17/2, and core component TN 17-CC are designed as type (B) casks and manufactured to comply with the IAEA Regulations for the Safe Transport of Radioactive Materials, 1973. (J.P.N.)

Plant nutrient transporter regulation in arbuscular mycorrhizas

DEFF Research Database (Denmark)

Burleigh, Stephen; Bechmann, I.E.

2002-01-01

of nutrition. Their down-regulation in mycorrhizal roots, therefore, would be predicted as a result of symbiotic function. A variety of studies on Pi- Zn- and ammonium- or nitrate-transporter genes from two plant species indirectly support this model. For example, one study showed that the expression...... of the high-affinity Pi-transporter MtPT2 within mycorrhizal roots of Medicago truncatula was inversely correlated with the concentration of P within the shoots, which suggested that P supply from the fungus influenced this gene's expression. However, there is some evidence that these plant nutrient...

Multiple conformational states of DnaA protein regulate its interaction with DnaA boxes in the initiation of DNA replication.

Science.gov (United States)

Patel, Meera J; Bhatia, Lavesh; Yilmaz, Gulden; Biswas-Fiss, Esther E; Biswas, Subhasis B

2017-09-01

DnaA protein is the initiator of genomic DNA replication in prokaryotes. It binds to specific DNA sequences in the origin of DNA replication and unwinds small AT-rich sequences downstream for the assembly of the replisome. The mechanism of activation of DnaA that enables it to bind and organize the origin DNA and leads to replication initiation remains unclear. In this study, we have developed double-labeled fluorescent DnaA probes to analyze conformational states of DnaA protein upon binding DNA, nucleotide, and Soj sporulation protein using Fluorescence Resonance Energy Transfer (FRET). Our studies demonstrate that DnaA protein undergoes large conformational changes upon binding to substrates and there are multiple distinct conformational states that enable it to initiate DNA replication. DnaA protein adopted a relaxed conformation by expanding ~15Å upon binding ATP and DNA to form the ATP·DnaA·DNA complex. Hydrolysis of bound ATP to ADP led to a contraction of DnaA within the complex. The relaxed conformation of DnaA is likely required for the formation of the multi-protein ATP·DnaA·DNA complex. In the initiation of sporulation, Soj binding to DnaA prevented relaxation of its conformation. Soj·ADP appeared to block the activation of DnaA, suggesting a mechanism for Soj·ADP in switching initiation of DNA replication to sporulation. Our studies demonstrate that multiple conformational states of DnaA protein regulate its binding to DNA in the initiation of DNA replication. Copyright © 2017 Elsevier B.V. All rights reserved.

Road Transport Management System (RTMS): a self regulation initiative in heavy vehicle transport in South Africa

CSIR Research Space (South Africa)

Nordengen, Paul A

2007-07-01

Full Text Available This paper describes the most recent developments of an initiative to introduce meaningful self-regulation in the heavy vehicle transport industry through a Road Transport Management System (RTMS) with the aim of contributing to the road authorities...

Regulations for the Safe Transport of Radioactive Material, 2009 ed. Safety Requirements

International Nuclear Information System (INIS)

2009-01-01

This publication establishes the regulations that are applied to the transport of radioactive material by all modes of transport on land, water or in the air, including transport that is incidental to the use of the radioactive material. The objective and scope of the regulations are described in detail as well as the range of their application. The publication provides requirements useful to governments, regulators, operators of nuclear and radiation facilities, carriers, users of radiation sources and cargo handling personnel. Contents: 1. Introduction; 2. Definitions; 3. General provisions; 4. Activity limits and classification; 5. Requirements and controls for transport; 6. Requirements for radioactive materials and for packagings and packages; 7. Test procedures; 8. Approval and administrative requirements; Annex I: Summary of approval and prior notification requirements; Annex II: Conversion factors and prefixes.

Regulations for the safe transport of radioactive material

International Nuclear Information System (INIS)

1995-01-01

Regulations and rules for the safe transport of radioactive materials by all kinds of conveyance are offered. Different types of packages and the conditions associated with the methods of safe packaging are given

Regulations for the Safe Transport of Radioactive Materials. 1964 Revised Edition

International Nuclear Information System (INIS)

1965-01-01

In 1961 the International Atomic Energy Agency, within the framework of its statutory functions and in accordance with recommendations made by its Preparatory Commission and by the Economic and Social Council of the United Nations, published safety regulations which could be applied to the national and international transport of radio active materials by all means of transport. At the same time, the Director General of the Agency indicated that these regulations would be revised at appropriate intervals in consultation with Member States and the organizations concerned and invited suggestions for their improvement in the light of experience and increased knowledge. In preparing the revised regulations presented in this document, the Agency has received considerable support from its Member States and the organizations concerned, which have made extensive studies and suggestions in order to assist in its work. The Agency also convened several meetings of experts from its Member States and of representatives of a number of international organizations, and has been represented in several meetings convened by those organizations. In publishing the revised transport regulations which result from that co-ordinated effort, the Agency aims at proposing a lasting framework of principles and rules, complemented by appropriate technical data, acceptable for the safe transport of radio active materials by air, land and water. In particular, the developments which have been introduced concerning the packaging requirements, the nuclear safety criteria for the transport of fissile materials and the methods for testing packages should facilitate the international acceptance of packages by the authorities concerned. The Board of Governors of the Agency approved the revised regulations in June and September 1964. It authorized the Director General to apply them, as appropriate, to Agency operations and Agency assisted operations and to recommend to Member States and to the

Impacts of transportation regulations on spent fuel and high level waste cask design

International Nuclear Information System (INIS)

Lake, W.H.

1992-01-01

The regulation of radioactive material transport has a long and successful history. Prior to 1966, these activities were regulated by the Interstate Commerce Commission (ICC) Bureau of Explosives (the ICC was predecessor to the Department of Transportation (DOT)). In 1966, the Atomic Energy Commission (AEC) developed what is now 10 CFR 71, concurrently with the development of similar international standards. In 1975, the AEC was reorganized and the Nuclear Regulatory Commission (NRC) was established as an independent regulatory commission. The NRC was given responsibility for the regulation of commercial use of radioactive materials, including transportation. This paper discusses various aspects of the NRC's role in the transport of radioactive material as well as its role in the design and certification of casks necessary to the transport of this material

Frequent down-regulation of ABC transporter genes in prostate cancer.

Science.gov (United States)

Demidenko, Rita; Razanauskas, Deividas; Daniunaite, Kristina; Lazutka, Juozas Rimantas; Jankevicius, Feliksas; Jarmalaite, Sonata

2015-10-12

ATP-binding cassette (ABC) transporters are transmembrane proteins responsible for the efflux of a wide variety of substrates, including steroid metabolites, through the cellular membranes. For better characterization of the role of ABC transporters in prostate cancer (PCa) development, the profile of ABC transporter gene expression was analyzed in PCa and noncancerous prostate tissues (NPT). TaqMan Low Density Array (TLDA) human ABC transporter plates were used for the gene expression profiling in 10 PCa and 6 NPT specimens. ABCB1 transcript level was evaluated in a larger set of PCa cases (N = 78) and NPT (N = 15) by real-time PCR, the same PCa cases were assessed for the gene promoter hypermethylation by methylation-specific PCR. Expression of eight ABC transporter genes (ABCA8, ABCB1, ABCC6, ABCC9, ABCC10, ABCD2, ABCG2, and ABCG4) was significantly down-regulated in PCa as compared to NPT, and only two genes (ABCC4 and ABCG1) were up-regulated. Down-regulation of ABC transporter genes was prevalent in the TMPRSS2-ERG-negative cases. A detailed analysis of ABCB1 expression confirmed TLDA results: a reduced level of the transcript was identified in PCa in comparison to NPT (p = 0.048). Moreover, the TMPRSS2-ERG-negative PCa cases showed significantly lower expression of ABCB1 in comparison to NPT (p = 0.003) or the fusion-positive tumors (p = 0.002). Promoter methylation of ABCB1 predominantly occurred in PCa and was rarely detected in NPT (p ABC transporter genes in PCa, especially in the TMPRSS2-ERG-negative tumors.

Regulatory practices of radiation safety of SNF transportation in Russia

International Nuclear Information System (INIS)

Kuryndina, Lidia; Kuryndin, Anton; Stroganov, Anatoly

2008-01-01

This paper overviews current regulatory practices for the assurance of nuclear and radiation safety during railway transportation of SNF on the territory of Russian Federation from NPPs to longterm-storage of reprocessing sites. The legal and regulatory requirements (mostly compliant with IAEA ST-1), licensing procedure for NM transportation are discussed. The current procedure does not require a regulatory approval for each particular shipment if the SNF fully comply with the Rosatom's branch standard and is transported in approved casks. It has been demonstrated that SNF packages compliant with the branch standard, which is knowingly provide sufficient safety margin, will conform to the federal level regulations. The regulatory approval is required if a particular shipment does not comply with the branch standard. In this case, the shipment can be approved only after regulatory review of Applicant's documents to demonstrate that the shipment still conformant to the higher level (federal) regulations. The regulatory review frequently needs a full calculation test of the radiation safety assurance. This test can take a lot of time. That's why the special calculation tools were created in SEC NRS. These tools aimed for precision calculation of the radiation safety parameters by SNF transportation use preliminary calculated Green's functions. Such approach allows quickly simulate any source distribution and optimize spent fuel assemblies placement in cask due to the transport equation property of linearity relatively the source. The short description of calculation tools are presented. Also, the paper discusses foreseen implications related to transportation of mixed-oxide SNF. (author)

SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation

DEFF Research Database (Denmark)

Kristensen, Anders S; Andersen, Jacob; Jørgensen, Trine N

2011-01-01

The neurotransmitter transporters (NTTs) belonging to the solute carrier 6 (SLC6) gene family (also referred to as the neurotransmitter-sodium-symporter family or Na(+)/Cl(-)-dependent transporters) comprise a group of nine sodium- and chloride-dependent plasma membrane transporters...... for the monoamine neurotransmitters serotonin (5-hydroxytryptamine), dopamine, and norepinephrine, and the amino acid neurotransmitters GABA and glycine. The SLC6 NTTs are widely expressed in the mammalian brain and play an essential role in regulating neurotransmitter signaling and homeostasis by mediating uptake...... of released neurotransmitters from the extracellular space into neurons and glial cells. The transporters are targets for a wide range of therapeutic drugs used in treatment of psychiatric diseases, including major depression, anxiety disorders, attention deficit hyperactivity disorder and epilepsy...

Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel

Science.gov (United States)

Marunaka, Yoshinori; Niisato, Naomi; Taruno, Akiyuki; Ohta, Mariko; Miyazaki, Hiroaki; Hosogi, Shigekuni; Nakajima, Ken-ichi; Kusuzaki, Katsuyuki; Ashihara, Eishi; Nishio, Kyosuke; Iwasaki, Yoshinobu; Nakahari, Takashi; Kubota, Takahiro

2011-01-01

Renal epithelial Na+ transport plays an important role in homeostasis of our body fluid content and blood pressure. Further, the Na+ transport in alveolar epithelial cells essentially controls the amount of alveolar fluid that should be kept at an appropriate level for normal gas exchange. The epithelial Na+ transport is generally mediated through two steps: (1) the entry step of Na+ via epithelial Na+ channel (ENaC) at the apical membrane and (2) the extrusion step of Na+ via the Na+, K+-ATPase at the basolateral membrane. In general, the Na+ entry via ENaC is the rate-limiting step. Therefore, the regulation of ENaC plays an essential role in control of blood pressure and normal gas exchange. In this paper, we discuss two major factors in ENaC regulation: (1) activity of individual ENaC and (2) number of ENaC located at the apical membrane. PMID:22028593

Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores.

Science.gov (United States)

Elosegui-Artola, Alberto; Andreu, Ion; Beedle, Amy E M; Lezamiz, Ainhoa; Uroz, Marina; Kosmalska, Anita J; Oria, Roger; Kechagia, Jenny Z; Rico-Lastres, Palma; Le Roux, Anabel-Lise; Shanahan, Catherine M; Trepat, Xavier; Navajas, Daniel; Garcia-Manyes, Sergi; Roca-Cusachs, Pere

2017-11-30

YAP is a mechanosensitive transcriptional activator with a critical role in cancer, regeneration, and organ size control. Here, we show that force applied to the nucleus directly drives YAP nuclear translocation by decreasing the mechanical restriction of nuclear pores to molecular transport. Exposure to a stiff environment leads cells to establish a mechanical connection between the nucleus and the cytoskeleton, allowing forces exerted through focal adhesions to reach the nucleus. Force transmission then leads to nuclear flattening, which stretches nuclear pores, reduces their mechanical resistance to molecular transport, and increases YAP nuclear import. The restriction to transport is further regulated by the mechanical stability of the transported protein, which determines both active nuclear transport of YAP and passive transport of small proteins. Our results unveil a mechanosensing mechanism mediated directly by nuclear pores, demonstrated for YAP but with potential general applicability in transcriptional regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulation of microtubule-based transport by MAP4

Science.gov (United States)

Semenova, Irina; Ikeda, Kazuho; Resaul, Karim; Kraikivski, Pavel; Aguiar, Mike; Gygi, Steven; Zaliapin, Ilya; Cowan, Ann; Rodionov, Vladimir

2014-01-01

Microtubule (MT)-based transport of organelles driven by the opposing MT motors kinesins and dynein is tightly regulated in cells, but the underlying molecular mechanisms remain largely unknown. Here we tested the regulation of MT transport by the ubiquitous protein MAP4 using Xenopus melanophores as an experimental system. In these cells, pigment granules (melanosomes) move along MTs to the cell center (aggregation) or to the periphery (dispersion) by means of cytoplasmic dynein and kinesin-2, respectively. We found that aggregation signals induced phosphorylation of threonine residues in the MT-binding domain of the Xenopus MAP4 (XMAP4), thus decreasing binding of this protein to MTs. Overexpression of XMAP4 inhibited pigment aggregation by shortening dynein-dependent MT runs of melanosomes, whereas removal of XMAP4 from MTs reduced the length of kinesin-2–dependent runs and suppressed pigment dispersion. We hypothesize that binding of XMAP4 to MTs negatively regulates dynein-dependent movement of melanosomes and positively regulates kinesin-2–based movement. Phosphorylation during pigment aggregation reduces binding of XMAP4 to MTs, thus increasing dynein-dependent and decreasing kinesin-2–dependent motility of melanosomes, which stimulates their accumulation in the cell center, whereas dephosphorylation of XMAP4 during dispersion has an opposite effect. PMID:25143402

Paroxetine prevented the down-regulation of astrocytic L-Glu transporters in neuroinflammation

Directory of Open Access Journals (Sweden)

Koki Fujimori

2015-01-01

Full Text Available The extracellular L-glutamate (L-Glu concentration is elevated in neuroinflammation, thereby causing excitotoxicity. One of the mechanisms is down-regulation of astrocyte L-Glu transporters. Some antidepressants have anti-inflammatory effects. We therefore investigated effects of various antidepressants on the down-regulation of astrocyte L-Glu transporters in the in vitro neuroinflammation model. Among these antidepressants, only paroxetine was effective. We previously demonstrated that the down-regulation of astrocyte L-Glu transporters was caused by L-Glu released from activated microglia. We here clarified that only paroxetine inhibited L-Glu release from microglia. This is the novel action of paroxetine, which may bring advantages on the therapy of neuroinflammation.

Visualization of SV2A conformations in situ by the use of Protein Tomography

International Nuclear Information System (INIS)

Lynch, Berkley A.; Matagne, Alain; Braennstroem, Annika; Euler, Anne von; Jansson, Magnus; Hauzenberger, Elenor; Soederhaell, J. Arvid

2008-01-01

The synaptic vesicle protein 2A (SV2A), the brain-binding site of the anti-epileptic drug levetiracetam (LEV), has been characterized by Protein Tomography TM . We identified two major conformations of SV2A in mouse brain tissue: first, a compact, funnel-structure with a pore-like opening towards the cytoplasm; second, a more open, V-shaped structure with a cleft-like opening towards the intravesicular space. The large differences between these conformations suggest a high degree of flexibility and support a valve-like mechanism consistent with the postulated transporter role of SV2A. These two conformations are represented both in samples treated with LEV, and in saline-treated samples, which indicates that LEV binding does not cause a large-scale conformational change of SV2A, or lock a specific conformational state of the protein. This study provides the first direct structural data on SV2A, and supports a transporter function suggested by sequence homology to MFS class of transporter proteins

Regulations for the safe transport of radioactive materials. Notes on certain aspects of the regulations

International Nuclear Information System (INIS)

1961-01-01

The notes attempt to provide some broad general guidance to users as to the purpose of the regulations and their working out in practice. They contain also the scientific background to the classification of radioisotopes for transport purposes given in the regulations. Furthermore, an approach was made to the difficult question of design of containers in relation to the factors that have to be taken into account by competent authorities in approving Type B containers, with a view both to helping those concerned on both sides of this transport problem, and to stimulating further thought on the subject, in order to build up a corpus of practical experience in this field.

Protein Kinases C-Mediated Regulations of Drug Transporter Activity, Localization and Expression

Directory of Open Access Journals (Sweden)

Abdullah Mayati

2017-04-01

Full Text Available Drug transporters are now recognized as major actors in pharmacokinetics, involved notably in drug–drug interactions and drug adverse effects. Factors that govern their activity, localization and expression are therefore important to consider. In the present review, the implications of protein kinases C (PKCs in transporter regulations are summarized and discussed. Both solute carrier (SLC and ATP-binding cassette (ABC drug transporters can be regulated by PKCs-related signaling pathways. PKCs thus target activity, membrane localization and/or expression level of major influx and efflux drug transporters, in various normal and pathological types of cells and tissues, often in a PKC isoform-specific manner. PKCs are notably implicated in membrane insertion of bile acid transporters in liver and, in this way, are thought to contribute to cholestatic or choleretic effects of endogenous compounds or drugs. The exact clinical relevance of PKCs-related regulation of drug transporters in terms of drug resistance, pharmacokinetics, drug–drug interactions and drug toxicity remains however to be precisely determined. This issue is likely important to consider in the context of the development of new drugs targeting PKCs-mediated signaling pathways, for treating notably cancers, diabetes or psychiatric disorders.

Conformational Clusters of Phosphorylated Tyrosine.

Science.gov (United States)

Abdelrasoul, Maha; Ponniah, Komala; Mao, Alice; Warden, Meghan S; Elhefnawy, Wessam; Li, Yaohang; Pascal, Steven M

2017-12-06

Tyrosine phosphorylation plays an important role in many cellular and intercellular processes including signal transduction, subcellular localization, and regulation of enzymatic activity. In 1999, Blom et al., using the limited number of protein data bank (PDB) structures available at that time, reported that the side chain structures of phosphorylated tyrosine (pY) are partitioned into two conserved conformational clusters ( Blom, N.; Gammeltoft, S.; Brunak, S. J. Mol. Biol. 1999 , 294 , 1351 - 1362 ). We have used the spectral clustering algorithm to cluster the increasingly growing number of protein structures with pY sites, and have found that the pY residues cluster into three distinct side chain conformations. Two of these pY conformational clusters associate strongly with a narrow range of tyrosine backbone conformation. The novel cluster also highly correlates with the identity of the n + 1 residue, and is strongly associated with a sequential pYpY conformation which places two adjacent pY side chains in a specific relative orientation. Further analysis shows that the three pY clusters are associated with distinct distributions of cognate protein kinases.

SOR/89-426, Transport Packaging of Radioactive Materials Regulations, amendment

International Nuclear Information System (INIS)

1989-01-01

These Regulations of 24 August 1989 amend the Transport Packaging of Radioactive Materials Regulations by clarifying the text and specifying certain requirements. In particular certain definitions have been replaced, namely those of ''Fissile Class III package'' and ''Special form radioactive material''. Also, this latter material may not be carried without a certificate attesting that it meets the requirements of the Regulations. (NEA)

Federal legal constraints on state and local regulation of radioactive materials transportation

International Nuclear Information System (INIS)

Reese, R.T.; Morris, F.A.; Welles, B.W.

1980-01-01

Within the last five years, the transportation of nuclear materials has experienced a rapid growth of state/local regulations. The federal government is responding to develop a legal basis for declaring these state/local regulations inconsistent and has proceeded to declare certain state regulations invalid. This paper summarizes the relevant legal doctrines, places these doctrines in the context of the federal regulatory framework and reaches conclusions about what forms of state and local regulation may be subject to possible preemptive initiatives and what regulations are unlikely candidates for federal actions. This paper also discusses an example of a preemptive initiative and a federal action. The initiative is contained in DOT's proposed rule on Highway Routing of Radioactive Materials. DOT's first general preemptive action under the Hazardous Materials Transportation Act is described with respect to decisions on Rhode Island's regulations regarding transportation of liquified natural and petroleum gases. There are still some issues that have not been clarified - the role of the federal government in the development and support of emergency response capabilities for nuclear and other hazardous materials, detailed shipment information, and state requirements for prenotifications

Conformal Nets II: Conformal Blocks

Science.gov (United States)

Bartels, Arthur; Douglas, Christopher L.; Henriques, André

2017-08-01

Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

The vital role of industry in contributing to the IAEA transport regulations

International Nuclear Information System (INIS)

Owen, G.

2004-01-01

Industry has taken a key role in the development of radioactive transport regulation for many years. There are two main parties that need consideration in the regulatory process: the 'public and worker' interest, this responsibility is represented by the regulators: the 'industry' interest, these parties by their nature, give priority to representing their own interests. Any amendment or review of the regulations benefits greatly from the industry perspective. The opposite ends of the 'spectrum of opinion' suggests that insufficient industry involvement may lead to uneconomic transport, whereas, insufficient Competent Authority involvement may lead to unsafe transport. These seemingly polarised views are considered and discussed, but it becomes clear that the two parties complement each other, both ensuring each remains grounded. The basis for a regulation that compares the costs directly with the benefit in terms of reduced risk to the public or employees is at the heart of successful regulation. This balance is fragile and sensitive and underlines the importance of a harmonised approach by both Industry and Competent Authorities

The vital role of industry in contributing to the IAEA transport regulations

Energy Technology Data Exchange (ETDEWEB)

Owen, G. [BNFL (United Kingdom)

2004-07-01

Industry has taken a key role in the development of radioactive transport regulation for many years. There are two main parties that need consideration in the regulatory process: the 'public and worker' interest, this responsibility is represented by the regulators: the 'industry' interest, these parties by their nature, give priority to representing their own interests. Any amendment or review of the regulations benefits greatly from the industry perspective. The opposite ends of the 'spectrum of opinion' suggests that insufficient industry involvement may lead to uneconomic transport, whereas, insufficient Competent Authority involvement may lead to unsafe transport. These seemingly polarised views are considered and discussed, but it becomes clear that the two parties complement each other, both ensuring each remains grounded. The basis for a regulation that compares the costs directly with the benefit in terms of reduced risk to the public or employees is at the heart of successful regulation. This balance is fragile and sensitive and underlines the importance of a harmonised approach by both Industry and Competent Authorities.

15 CFR 265.34 - Conformity with posted signs.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Conformity with posted signs. 265.34 Section 265.34 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade NATIONAL..., GAITHERSBURG, MARYLAND, AND BOULDER AND FORT COLLINS, COLORADO Buildings and Grounds § 265.34 Conformity with...

LHP1 Regulates H3K27me3 Spreading and Shapes the Three-Dimensional Conformation of the Arabidopsis Genome

KAUST Repository

Veluchamy, Alaguraj; Jé gu, Teddy; Ariel, Federico; Latrasse, David; Mariappan, Kiruthiga Gayathri; Kim, SoonKap; Crespi, Martin; Hirt, Heribert; Bergounioux, Catherine; Raynaud, Cé cile; Benhamed, Moussa

2016-01-01

Precise expression patterns of genes in time and space are essential for proper development of multicellular organisms. Dynamic chromatin conformation and spatial organization of the genome constitute a major step in this regulation to modulate developmental outputs. Polycomb repressive complexes (PRCs) mediate stable or flexible gene repression in response to internal and environmental cues. In Arabidopsis thaliana, LHP1 co-localizes with H3K27me3 epigenetic marks throughout the genome and interacts with PRC1 and PRC2 members as well as with a long noncoding RNA. Here, we show that LHP1 is responsible for the spreading of H3K27me3 towards the 3’ end of the gene body. We also identified a subset of LHP1-activated genes and demonstrated that LHP1 shapes local chromatin topology in order to control transcriptional co-regulation. Our work reveals a general role of LHP1 from local to higher conformation levels of chromatin configuration to determine its accessibility to define gene expression patterns.

LHP1 Regulates H3K27me3 Spreading and Shapes the Three-Dimensional Conformation of the Arabidopsis Genome.

Directory of Open Access Journals (Sweden)

Alaguraj Veluchamy

Full Text Available Precise expression patterns of genes in time and space are essential for proper development of multicellular organisms. Dynamic chromatin conformation and spatial organization of the genome constitute a major step in this regulation to modulate developmental outputs. Polycomb repressive complexes (PRCs mediate stable or flexible gene repression in response to internal and environmental cues. In Arabidopsis thaliana, LHP1 co-localizes with H3K27me3 epigenetic marks throughout the genome and interacts with PRC1 and PRC2 members as well as with a long noncoding RNA. Here, we show that LHP1 is responsible for the spreading of H3K27me3 towards the 3' end of the gene body. We also identified a subset of LHP1-activated genes and demonstrated that LHP1 shapes local chromatin topology in order to control transcriptional co-regulation. Our work reveals a general role of LHP1 from local to higher conformation levels of chromatin configuration to determine its accessibility to define gene expression patterns.

LHP1 Regulates H3K27me3 Spreading and Shapes the Three-Dimensional Conformation of the Arabidopsis Genome

KAUST Repository

Veluchamy, Alaguraj

2016-07-13

Precise expression patterns of genes in time and space are essential for proper development of multicellular organisms. Dynamic chromatin conformation and spatial organization of the genome constitute a major step in this regulation to modulate developmental outputs. Polycomb repressive complexes (PRCs) mediate stable or flexible gene repression in response to internal and environmental cues. In Arabidopsis thaliana, LHP1 co-localizes with H3K27me3 epigenetic marks throughout the genome and interacts with PRC1 and PRC2 members as well as with a long noncoding RNA. Here, we show that LHP1 is responsible for the spreading of H3K27me3 towards the 3’ end of the gene body. We also identified a subset of LHP1-activated genes and demonstrated that LHP1 shapes local chromatin topology in order to control transcriptional co-regulation. Our work reveals a general role of LHP1 from local to higher conformation levels of chromatin configuration to determine its accessibility to define gene expression patterns.

Experiences in certification of packages for transportation of fresh nuclear fuel in the context of new safety requirements established by IAEA regulations (IAEA-96 regulations, ST-1) for air transportation of nuclear materials (requirements to C-type packages)

Energy Technology Data Exchange (ETDEWEB)

Dudai, V.I.; Kovtun, A.D.; Matveev, V.Z.; Morenko, A.I.; Nilulin, V.M.; Shapovalov, V.I.; Yakushev, V.A.; Bobrovsky, V.S.; Rozhkov, V.V.; Agapov, A.M.; Kolesnikov, A.S. [Russian Federal Nuclear Centre - All-Russian Research Inst. of Experimental Physics, Sarov (Russian Federation)]|[JSC ' ' MSZ' ' , Electrostal (Russian Federation)]|[JSC ' ' NPCC' ' , Novosibirsk (Russian Federation)]|[Minatom of Russia, Moscow (Russian Federation)]|[Gosatomnadzor of Russia, Moscow (Russian Federation)

2004-07-01

Every year in Russia, a large amount of domestic and international transportation of fresh nuclear fuel (FNF) used in Russian and foreign energy and research atomic reactors and referred to fissile materials based on IAEA Regulations is performed. Here, bulk transportation is performed by air, and it concerns international transportation in particular. According to national ''Main Regulations for Safe Transport and physical Protection of Nuclear Materials (OPBZ- 83)'' and ''Regulations for the Safe Transport of Radioactive Materials'' of the International Atomic Energy Agency (IAEA Regulations), nuclear and radiation security under normal (accident free) and accident conditions of transport must be completely provided by the package design. In this context, high requirements to fissile packages exposed to heat and mechanical loads in transport accidents are imposed. A long-standing experience in accident free transportation of FM has shown that such approach to provide nuclear and radiation security pays for itself completely. Nevertheless, once in 10 years the International Atomic Energy Agency on every revision of the ''Regulations for the Safe Transport of Radioactive Materials'' places more stringent requirements upon the FM and transportation thereof, resulting from the objectively increasing risk associated with constant rise in volume and density of transportation, and also strained social and economical situation in a number of regions in the world. In the new edition of the IAEA Regulations (ST-1), published in 1996 and brought into force in 2001 (IAEA-96 Regulations), the requirements to FM packages conveyed by aircraft were radically changed. These requirements are completely presented in new Russian ''Regulations for the Safe Transport of Radioactive Materials'' (PBTRM- 2004) which will be brought into force in the time ahead.

The sigma-1 receptor modulates dopamine transporter conformation and cocaine binding and may thereby potentiate cocaine self-administration in rats.

Science.gov (United States)

Hong, Weimin Conrad; Yano, Hideaki; Hiranita, Takato; Chin, Frederick T; McCurdy, Christopher R; Su, Tsung-Ping; Amara, Susan G; Katz, Jonathan L

2017-07-07

The dopamine transporter (DAT) regulates dopamine (DA) neurotransmission by recapturing DA into the presynaptic terminals and is a principal target of the psychostimulant cocaine. The sigma-1 receptor (σ 1 R) is a molecular chaperone, and its ligands have been shown to modulate DA neuronal signaling, although their effects on DAT activity are unclear. Here, we report that the prototypical σ 1 R agonist (+)-pentazocine potentiated the dose response of cocaine self-administration in rats, consistent with the effects of the σR agonists PRE-084 and DTG (1,3-di- o -tolylguanidine) reported previously. These behavioral effects appeared to be correlated with functional changes of DAT. Preincubation with (+)-pentazocine or PRE-084 increased the B max values of [ 3 H]WIN35428 binding to DAT in rat striatal synaptosomes and transfected cells. A specific interaction between σ 1 R and DAT was detected by co-immunoprecipitation and bioluminescence resonance energy transfer assays. Mutational analyses indicated that the transmembrane domain of σ 1 R likely mediated this interaction. Furthermore, cysteine accessibility assays showed that σ 1 R agonist preincubation potentiated cocaine-induced changes in DAT conformation, which were blocked by the specific σ 1 R antagonist CM304. Moreover, σ 1 R ligands had distinct effects on σ 1 R multimerization. CM304 increased the proportion of multimeric σ 1 Rs, whereas (+)-pentazocine increased monomeric σ 1 Rs. Together these results support the hypothesis that σ 1 R agonists promote dissociation of σ 1 R multimers into monomers, which then interact with DAT to stabilize an outward-facing DAT conformation and enhance cocaine binding. We propose that this novel molecular mechanism underlies the behavioral potentiation of cocaine self-administration by σ 1 R agonists in animal models. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Dangerous goods regulations in Europe and worldwide inland navigation and other modes of transport

International Nuclear Information System (INIS)

Ridder, K.

1993-01-01

Since, for historical reasons, separate dangerous goods regulations were developed for each mode of transport, there now exist several different regulatory regimes. For Europe, and indeed the whole world, these uncoordinated regulations pose a serious problem. In my paper I will show 1) which regulations are applicable in Europe, 2) which role international transport organizations play and 3) which role the European Community plays. Special emphasis will be placed on inland navigation, since it is this mode of transport that will experience extensive changes during 1992. (J.P.N.)

Early vertebrate origin and diversification of small transmembrane regulators of cellular ion transport.

Science.gov (United States)

Pirkmajer, Sergej; Kirchner, Henriette; Lundell, Leonidas S; Zelenin, Pavel V; Zierath, Juleen R; Makarova, Kira S; Wolf, Yuri I; Chibalin, Alexander V

2017-07-15

Small transmembrane proteins such as FXYDs, which interact with Na + ,K + -ATPase, and the micropeptides that interact with sarco/endoplasmic reticulum Ca 2+ -ATPase play fundamental roles in regulation of ion transport in vertebrates. Uncertain evolutionary origins and phylogenetic relationships among these regulators of ion transport have led to inconsistencies in their classification across vertebrate species, thus hampering comparative studies of their functions. We discovered the first FXYD homologue in sea lamprey, a basal jawless vertebrate, which suggests small transmembrane regulators of ion transport emerged early in the vertebrate lineage. We also identified 13 gene subfamilies of FXYDs and propose a revised, phylogeny-based FXYD classification that is consistent across vertebrate species. These findings provide an improved framework for investigating physiological and pathophysiological functions of small transmembrane regulators of ion transport. Small transmembrane proteins are important for regulation of cellular ion transport. The most prominent among these are members of the FXYD family (FXYD1-12), which regulate Na + ,K + -ATPase, and phospholamban, sarcolipin, myoregulin and DWORF, which regulate the sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA). FXYDs and regulators of SERCA are present in fishes, as well as terrestrial vertebrates; however, their evolutionary origins and phylogenetic relationships are obscure, thus hampering comparative physiological studies. Here we discovered that sea lamprey (Petromyzon marinus), a representative of extant jawless vertebrates (Cyclostomata), expresses an FXYD homologue, which strongly suggests that FXYDs predate the emergence of fishes and other jawed vertebrates (Gnathostomata). Using a combination of sequence-based phylogenetic analysis and conservation of local chromosome context, we determined that FXYDs markedly diversified in the lineages leading to cartilaginous fishes (Chondrichthyes) and bony

15 CFR 758.5 - Conformity of documents and unloading of items.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Conformity of documents and unloading... REGULATIONS EXPORT CLEARANCE REQUIREMENTS § 758.5 Conformity of documents and unloading of items. (a) Purpose... country other than that of the ultimate consignee as stated on the export license. (b) Conformity of...

Steric exclusion and protein conformation determine the localization of plasma membrane transporters.

Science.gov (United States)

Bianchi, Frans; Syga, Łukasz; Moiset, Gemma; Spakman, Dian; Schavemaker, Paul E; Punter, Christiaan M; Seinen, Anne-Bart; van Oijen, Antoine M; Robinson, Andrew; Poolman, Bert

2018-02-05

The plasma membrane (PM) of Saccharomyces cerevisiae contains membrane compartments, MCC/eisosomes and MCPs, named after the protein residents Can1 and Pma1, respectively. Using high-resolution fluorescence microscopy techniques we show that Can1 and the homologous transporter Lyp1 are able to diffuse into the MCC/eisosomes, where a limited number of proteins are conditionally trapped at the (outer) edge of the compartment. Upon addition of substrate, the immobilized proteins diffuse away from the MCC/eisosomes, presumably after taking a different conformation in the substrate-bound state. Our data indicate that the mobile fraction of all integral plasma membrane proteins tested shows extremely slow Brownian diffusion through most of the PM. We also show that proteins with large cytoplasmic domains, such as Pma1 and synthetic chimera of Can1 and Lyp1, are excluded from the MCC/eisosomes. We hypothesize that the distinct localization patterns found for these integral membrane proteins in S. cerevisiae arises from a combination of slow lateral diffusion, steric exclusion, and conditional trapping in membrane compartments.

Fostering member state implementation of the IAEA's transport regulations

International Nuclear Information System (INIS)

Brittinger, M.T.M.; Wangler, M.E.

2004-01-01

Based on a 1959 mandate from the United Nations Economic and Social Council, international safety requirements are embodied in the ''Regulations for the Safe Transport of Radioactive Material'' that were first published by the International Atomic Energy Agency in 1961 and revised in 1967, 1973, 1985 and 1996 to keep them abreast of scientific and technical developments. The requirements are incorporated into the regulatory documents of the International Civil Aviation Organization for air transport, and the International Maritime Organization for marine transport. As the requirements of the latter documents are legally-binding for the member states of the corresponding organizations, the IAEA safety requirements thus also become mandatory in those countries. The same situation applies for the surface modes in Europe, by means of the regulatory documents of the European Community for rail, road and inland waterways. Nevertheless, the IAEA has not relaxed its efforts to ensure that its Transport Regulations stay abreast of scientific and technical developments; on the contrary, it has been undertaking a regular and vigorous review of its safety requirements, and continues to do so with the assistance of Member States and relevant international organizations. Beyond providing the regulatory basis for the safe transport of radioactive material, however, the IAEA also offers a work programme under which it assists Member States in complying with the regulatory requirements. This assistance comes in the form of providing training on the safety requirements, and publishing documents that facilitate the exchange of information

De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder.

Science.gov (United States)

Hamilton, P J; Campbell, N G; Sharma, S; Erreger, K; Herborg Hansen, F; Saunders, C; Belovich, A N; Sahai, M A; Cook, E H; Gether, U; McHaourab, H S; Matthies, H J G; Sutcliffe, J S; Galli, A

2013-12-01

De novo genetic variation is an important class of risk factors for autism spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has identified a novel de novo missense mutation in the human dopamine (DA) transporter (hDAT) gene, which results in a Thr to Met substitution at site 356 (hDAT T356M). The dopamine transporter (DAT) is a presynaptic membrane protein that regulates dopaminergic tone in the central nervous system by mediating the high-affinity reuptake of synaptically released DA, making it a crucial regulator of DA homeostasis. Here, we report the first functional, structural and behavioral characterization of an ASD-associated de novo mutation in the hDAT. We demonstrate that the hDAT T356M displays anomalous function, characterized as a persistent reverse transport of DA (substrate efflux). Importantly, in the bacterial homolog leucine transporter, substitution of A289 (the homologous site to T356) with a Met promotes an outward-facing conformation upon substrate binding. In the substrate-bound state, an outward-facing transporter conformation is required for substrate efflux. In Drosophila melanogaster, the expression of hDAT T356M in DA neurons-lacking Drosophila DAT leads to hyperlocomotion, a trait associated with DA dysfunction and ASD. Taken together, our findings demonstrate that alterations in DA homeostasis, mediated by aberrant DAT function, may confer risk for ASD and related neuropsychiatric conditions.

Regulations for the safe transport of radioactive materials. 1973 revised edition (as amended).

International Nuclear Information System (INIS)

1979-01-01

On the basis of a comprehensive review carried out by a panel of experts, a revised version of the International Atomic Energy Agency's Regulations for the Safe Transport of Radioactive Materials was approved by the Board of Governors in September 1972 and published in April 1973 as Safety Series No.6 - 1973 Revised Edition. Minor amendments, together with a number of changes of detail were promulgated by the Director General in 1975 and 1977. In October 1978, the Standing Advisory Group on the Safe Transport of Radioactive Materials, established by the Director General in 1977, reviewed and recommended a small number of additional amendments. The recommendations of SAGSTRAM were subsequently accepted by the Director General. All these minor amendments and changes of detail are incorporated in the present text of the Regulations. The purpose of these Regulations is to establish standards of safety which provide an acceptable level of control of the radiation hazards to persons, property and the environment that are associated with the transport of radioactive material. They apply to the transport by land, water or air, including transport on own account, of radioactive material other than that which is an integral part of the means of transport. Transport includes any operation incidental to the whole course of carriage, such as loading, unloading and storage in transit. The term includes both normal transport and that under accident conditions

The role of volume-sensitive ion transport systems in regulation of epithelial transport

DEFF Research Database (Denmark)

Hoffmann, Else Kay; Schettino, T; Marshall, W S

2007-01-01

This review focuses on using the knowledge on volume-sensitive transport systems in Ehrlich ascites tumour cells and NIH-3T3 cells to elucidate osmotic regulation of salt transport in epithelia. Using the intestine of the European eel (Anguilla anguilla) (an absorptive epithelium of the type...... on the apical side and the Na+/K+ ATPase, NKCC1 and a K+ channel on the basolateral side. Osmotic control of Cl- secretion across the operculum epithelium includes: (i) hyperosmotic shrinkage activation of NKCC1 via PKC, MLCK, p38, OSR1 and SPAK; (ii) deactivation of NKCC by hypotonic cell swelling...

Conformity and Internalisation in a Participative Decision Making Process

International Nuclear Information System (INIS)

Bombaerts, Gunter

2003-01-01

This paper reflects upon the stretching concept of the RISCOM model. We agree with the Habermassian point of departure that a competent speaker makes validity claims on truth, legitimacy and authenticity and partially with the Dialogue Project's conclusions that opening the black box of science is not possible in a decision making process (DMP) on a highly technical issue. Accordingly, we see an important role for a regulator to stretch the implementer, i.e. balance commercial and guardian ethics in the DMP. However, some caution is needed. Conformity studies indicate the large influence of group norms on individuals. When individuals lack personal reference frames of a particular issue they are prone to conform. The more values are shared, the more group members are convinced of the correctness. And social psychology shows more. In studies on persuasion, a difference between compliance and internalisation is made. Compliance is attained from rewards and coercive sources of power, whereas internalisation originates from expertise, legitimacy and credibility. Because of the shift to legitimacy and authenticity in the DMP, alignment of the norms and internalisation of discussed values becomes more apparent in the RISCOM participation model. Conformity reactions and possible internalisation are normal aspect of human interaction and not necessarily a negative aspect of public involvement. But keeping the importance of conformity in mind, a few consequences can be mentioned with regard to the relation implementer-regulator, the non-participation majority, and non-participating critics. The new role of the regulator and the involved public in the RISCOM mode] cannot absolutely avoid the risks due to conformity, it can only decrease the conformity influence

Dynamic conformational change regulates the protein-DNA recognition: an investigation on binding of a Y-family polymerase to its target DNA.

Directory of Open Access Journals (Sweden)

Xiakun Chu

2014-09-01

Full Text Available Protein-DNA recognition is a central biological process that governs the life of cells. A protein will often undergo a conformational transition to form the functional complex with its target DNA. The protein conformational dynamics are expected to contribute to the stability and specificity of DNA recognition and therefore may control the functional activity of the protein-DNA complex. Understanding how the conformational dynamics influences the protein-DNA recognition is still challenging. Here, we developed a two-basin structure-based model to explore functional dynamics in Sulfolobus solfataricus DNA Y-family polymerase IV (DPO4 during its binding to DNA. With explicit consideration of non-specific and specific interactions between DPO4 and DNA, we found that DPO4-DNA recognition is comprised of first 3D diffusion, then a short-range adjustment sliding on DNA and finally specific binding. Interestingly, we found that DPO4 is under a conformational equilibrium between multiple states during the binding process and the distributions of the conformations vary at different binding stages. By modulating the strength of the electrostatic interactions, the flexibility of the linker, and the conformational dynamics in DPO4, we drew a clear picture on how DPO4 dynamically regulates the DNA recognition. We argue that the unique features of flexibility and conformational dynamics in DPO4-DNA recognition have direct implications for low-fidelity translesion DNA synthesis, most of which is found to be accomplished by the Y-family DNA polymerases. Our results help complete the description of the DNA synthesis process for the Y-family polymerases. Furthermore, the methods developed here can be widely applied for future investigations on how various proteins recognize and bind specific DNA substrates.

SPAK Dependent Regulation of Peptide Transporters PEPT1 and PEPT2

Directory of Open Access Journals (Sweden)

Jamshed Warsi

2014-10-01

Full Text Available Background/Aims: SPAK (STE20-related proline/alanine-rich kinase is a powerful regulator of renal tubular ion transport and blood pressure. Moreover, SPAK contributes to the regulation of cell volume. Little is known, however, about a role of SPAK in the regulation or organic solutes. The present study thus addressed the influence of SPAK on the peptide transporters PEPT1 and PEPT2. Methods: To this end, cRNA encoding PEPT1 or PEPT2 were injected into Xenopus laevis oocytes without or with additional injection of cRNA encoding wild-type, SPAK, WNK1 insensitive inactive T233ASPAK, constitutively active T233ESPAK, and catalytically inactive D212ASPAK. Electrogenic peptide (glycine-glycine transport was determined by dual electrode voltage clamp and PEPT2 protein abundance in the cell membrane by chemiluminescence. Intestinal electrogenic peptide transport was estimated from peptide induced current in Ussing chamber experiments of jejunal segments isolated from gene targeted mice expressing SPAK resistant to WNK-dependent activation (spaktg/tg and respective wild-type mice (spak+/+. Results: In PEPT1 and in PEPT2 expressing oocytes, but not in oocytes injected with water, the dipeptide gly-gly (2 mM generated an inward current, which was significantly decreased following coexpression of SPAK. The effect of SPAK on PEPT1 was mimicked by T233ESPAK, but not by D212ASPAK or T233ASPAK. SPAK decreased maximal peptide induced current of PEPT1. Moreover, SPAK decreased carrier protein abundance in the cell membrane of PEPT2 expressing oocytes. In intestinal segments gly-gly generated a current, which was significantly higher in spaktg/tg than in spak+/+ mice. Conclusion: SPAK is a powerful regulator of peptide transporters PEPT1 and PEPT2.

The development of the IAEA transport regulations and its implementation in Europe

International Nuclear Information System (INIS)

Collin, F.W.

1987-01-01

The radiation protection principles are laid down in a binding from in IAEA SS No 9. Regulations of world-wide validity (and, hence, for Europe) are IMO/IMDG Code for sea-going traffic, and ICAO/Technical regulations or IATA/Hazardous goods transport regulations, resp. for air traffic. The regulations by the organizations ADR, RID, ADN, ADNR, and CMEA are valid as transfrontier regulations in Europe. (DG) [de

The impact of the new IAEA transport regulations for the safe transport of radioactive materials on package design and transport

International Nuclear Information System (INIS)

Schneider, K.

1989-01-01

In April 1985 the 1985 Edition of the IAEA Safety Series No. 6, Regulations for the Safe Transport of Radioactive Materials, was issued. This is a completely revised edition which shall come into force internationally in the late eighties. This edition will supersede the 1973 (As Amended, 1979) edition. A paragraph by paragraph comparison is carried through, followed by a consideration on the impact on general requirements for packaging and transport. A detailed estimate on packaging design and transport is performed for typical products of the nuclear fuel cycle. The major practical consequences likely to be encountered are presented

31 CFR 407.5 - Conformity with signs and directions.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Conformity with signs and directions. 407.5 Section 407.5 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... TREASURY ANNEX § 407.5 Conformity with signs and directions. Persons in and on the property shall comply...

Quality management in the regulation of radioactive material transport

International Nuclear Information System (INIS)

Barenghi, Leonardo; Capadona, Nancy M.; Lopez Vietri, Jorge R.; Panzino, Marina; Ceballos, Jorge

2006-01-01

The paper describes the quality management procedure used by the Argentine Nuclear Regulatory Authority to establish the regulations concerning the safe transport of radioactive materials. The quality management system is based on the family of the ISO 9000 norms [es

Flavonoids act as negative regulators of auxin transport in vivo in arabidopsis

Science.gov (United States)

Brown, D. E.; Rashotte, A. M.; Murphy, A. S.; Normanly, J.; Tague, B. W.; Peer, W. A.; Taiz, L.; Muday, G. K.

2001-01-01

Polar transport of the plant hormone auxin controls many aspects of plant growth and development. A number of synthetic compounds have been shown to block the process of auxin transport by inhibition of the auxin efflux carrier complex. These synthetic auxin transport inhibitors may act by mimicking endogenous molecules. Flavonoids, a class of secondary plant metabolic compounds, have been suggested to be auxin transport inhibitors based on their in vitro activity. The hypothesis that flavonoids regulate auxin transport in vivo was tested in Arabidopsis by comparing wild-type (WT) and transparent testa (tt4) plants with a mutation in the gene encoding the first enzyme in flavonoid biosynthesis, chalcone synthase. In a comparison between tt4 and WT plants, phenotypic differences were observed, including three times as many secondary inflorescence stems, reduced plant height, decreased stem diameter, and increased secondary root development. Growth of WT Arabidopsis plants on naringenin, a biosynthetic precursor to those flavonoids with auxin transport inhibitor activity in vitro, leads to a reduction in root growth and gravitropism, similar to the effects of synthetic auxin transport inhibitors. Analyses of auxin transport in the inflorescence and hypocotyl of independent tt4 alleles indicate that auxin transport is elevated in plants with a tt4 mutation. In hypocotyls of tt4, this elevated transport is reversed when flavonoids are synthesized by growth of plants on the flavonoid precursor, naringenin. These results are consistent with a role for flavonoids as endogenous regulators of auxin transport.

Federal, state, and local regulation of radioactive-waste transportation: Progress toward a definition of regulatory authority

International Nuclear Information System (INIS)

Livingston-Behan, E.A.

1986-01-01

The supremacy clause, the commerce clause, and the equal-protection guarantees of the U.S. Constitution establish the basic framework for defining the authority of Federal, State, and local governments to regulate the transportation of radioactive waste. Court decisions and advisory rulings of the U.S. Department of Transportation (DOT) suggest that State and local regulation of the transportation of spent nuclear fuel and high-level radioactive waste is precluded under supremacy-clause principles to the extent that such regulation addresses nuclear safety or aspects of transportation that are already specifically regulated by the Federal government. Even where State and local requirements are found to be valid under the supremacy clause, they must still satisfy constitutional requirements under the commerce and equal-protection clauses. Despite stringent standards of review, State and local transportation requirements have been upheld where directly related to the traditional exercise of police powers in the area of transportation. Legitimate State and local police-power activities identified to date by the DOT and the courts include inspection and enforcement, immediate accident reporting, local regulation of traffic, and certain time-of-day curfews. The extent to which State and local permitting requirements and license fees may be determined valid by the DOT and the courts remains unclear. Continued clarification by the DOT and the courts as to the validity of permits and fees will serve to further define the appropriate balance for Federal, State, and local regulation of radioactive-waste transportation

36 CFR 504.4 - Conformity with signs and emergency directions.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Conformity with signs and emergency directions. 504.4 Section 504.4 Parks, Forests, and Public Property SMITHSONIAN INSTITUTION RULES AND REGULATIONS GOVERNING SMITHSONIAN INSTITUTION BUILDINGS AND GROUNDS § 504.4 Conformity with signs...

Glucose transporters: expression, regulation and cancer

Directory of Open Access Journals (Sweden)

RODOLFO A. MEDINA

2002-01-01

Full Text Available Mammalian cells depend on glucose as a major substrate for energy production. Glucose is transported into the cell via facilitative glucose transporters (GLUT present in all cell types. Many GLUT isoforms have been described and their expression is cell-specific and subject to hormonal and environmental control. The kinetic properties and substrate specificities of the different isoforms are specifically suited to the energy requirements of the particular cell types. Due to the ubiquitousness of these transporters, their differential expression is involved in various disease states such as diabetes, ischemia and cancer. The majority of cancers and isolated cancer cell lines over-express the GLUT family members which are present in the respective tissue of origin under non-cancerous conditions. Moreover, due to the requirement of energy to feed uncontrolled proliferation, cancer cells often express GLUTs which under normal conditions would not be present in these tissues. This over-expression is predominantly associated with the likelihood of metastasis and hence poor patient prognosis. This article presents a review of the current literature on the regulation and expression of GLUT family members and has compiled clinical and research data on GLUT expression in human cancers and in isolated human cancer cell lines.

Regulations for safe transport of spent fuels from nuclear power plants in CMEA member countries. Part III

International Nuclear Information System (INIS)

Zizka, B.

1978-11-01

The regulations for safe transport of spent fuel from nuclear power plants in the CMEA member countries consist of general provisions, technical requirements for spent fuel transport, transport conditions, procedures for submitting reports on transport, regulations for transport and protection of radioactive material to be transported, procedures for customs clearance, technical and organizational measures for the prevention of hypothetical accidents and the elimination of their consequences. The bodies responsible for spent fuel transport in the CMEA member countries are listed. (J.B.)

7 CFR 500.4 - Conformity with signs and emergency directions.

Science.gov (United States)

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Conformity with signs and emergency directions. 500.4 Section 500.4 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH... Conformity with signs and emergency directions. Persons in and on property of the USNA shall comply with...

7 CFR 501.4 - Conformity with signs and emergency directions.

Science.gov (United States)

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Conformity with signs and emergency directions. 501.4 Section 501.4 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH... § 501.4 Conformity with signs and emergency directions. Persons in and on property of the Research...

7 CFR 502.4 - Conformity with signs and emergency directions.

Science.gov (United States)

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Conformity with signs and emergency directions. 502.4 Section 502.4 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH..., MARYLAND § 502.4 Conformity with signs and emergency directions. Persons in and on property of BARC shall...

75 FR 17253 - Revisions to the General Conformity Regulations

Science.gov (United States)

2010-04-05

... Part III Environmental Protection Agency 40 CFR Parts 51 and 93 Revisions to the General... under the minor source New Source Review (NSR) programs similar to the EPA's existing General Conformity... EPA is making two minor revisions to the definition. First, EPA is correcting the citation for the SIP...

Effect of External Electric Field on Substrate Transport of a Secondary Active Transporter.

Science.gov (United States)

Zhang, Ji-Long; Zheng, Qing-Chuan; Yu, Li-Ying; Li, Zheng-Qiang; Zhang, Hong-Xing

2016-08-22

Substrate transport across a membrane accomplished by a secondary active transporter (SAT) is essential to the normal physiological function of living cells. In the present research, a series of all-atom molecular dynamics (MD) simulations under different electric field (EF) strengths was performed to investigate the effect of an external EF on the substrate transport of an SAT. The results show that EF both affects the interaction between substrate and related protein's residues by changing their conformations and tunes the timeline of the transport event, which collectively reduces the height of energy barrier for substrate transport and results in the appearance of two intermediate conformations under the existence of an external EF. Our work spotlights the crucial influence of external EFs on the substrate transport of SATs and could provide a more penetrating understanding of the substrate transport mechanism of SATs.

Assessment of the application of the IAEA regulations for the safe transport of radioactive material

International Nuclear Information System (INIS)

1986-12-01

The IAEA, working with the individual Member States, undertook to examine the manner in which domestic, import, export and through-country shipments of radioactive materials are controlled and regulated worldwide. The information to be examined was collected by a questionnaire, which was sent to Member States in July 1984. Copies of the letter and the questionnaire are in Appendix I of this document. The follow-up letters, repeating the request to provide the IAEA with data and asking authorization to publish the data obtained through the questionnaire, were sent in February 1985 (Appendix II and III). By the end of June 1986 completed questionnaires had been received from 53 Member States. These Member States are listed in Appendix IV. The results of the examination are summarized in this report. The results indicate the important role the international organizations play in the transport of radioactive material. All the Member States involved in this examination regulate the transport of radioactive material within their country on the basis of international agreements, regulations and recommendations. The IAEA Regulations for the Safe Transport of Radioactive Material, Safety Series No. 6, is the ultimately controlling document since it serves as the basis for the radioactive material portions of other international transport documents (Appendix V) and since it is made directly binding in the regulations of many countries. In addition to the questions concerning the adoption of the regulations, some questions on the implementation of the transport regulations, e.g. on competent authorities and other regulatory bodies as well as quality assurance, were presented in the questionnaire. This report concerns only the adoption of the regulations

76 FR 7560 - Agency Information Collection Activities; Proposed Collection; Comment Request; Transportation...

Science.gov (United States)

2011-02-10

... Activities; Proposed Collection; Comment Request; Transportation Conformity Determinations for Federally... federally supported transportation activities are consistent with (``conform to'') the purpose of the state air quality implementation plan (SIP). Transportation activities include transportation plans...

Advisory material for the IAEA regulations for the safe transport of radioactive material. Safety guide

International Nuclear Information System (INIS)

2008-01-01

Since the first edition in 1961, the Regulations for the Safe Transport of Radioactive Material of the IAEA (IAEA Regulations) have served as the basis of safety for the transport of radioactive material worldwide. In the discussions leading to the first edition of the IAEA Regulations, it was realized that there was need for a publication to supplement the Regulations which could give information of individual provisions as to their purpose, their scientific background and how to apply them in practice. In response, the Agency published Safety Series No. 7, entitled, in its first edition in 1961, 'Notes on Certain Aspects of the Regulations'. An additional source of information on the Regulations, providing advice on 'how' the user should comply with them which could be augmented from time to time in the light of latest experience, was provided by the Agency, initially in relation to the 1973 edition of the Regulations. This was entitled 'Advisory Material for the IAEA Regulations for the Safe Transport of Radioactive Material' and designated Safety Series No. 37. This document is the result of combining the two Safety Series in a single publication. Thus the primary purpose of this publication is to provide guidance to users on proven and acceptable ways of complying with the Regulations. This Advisory Material is not a stand-alone text and it only has significance when used as a companion to the IAEA Safety Standards Series No. ST-1, Regulations for the Safe Transport of Radioactive Material (1996 edition)

Outside-In Signal Transmission by Conformational Changes in Integrin Mac-11

Science.gov (United States)

Lefort, Craig T.; Hyun, Young-Min; Schultz, Joanne B.; Law, Foon-Yee; Waugh, Richard E.; Knauf, Philip A.; Kim, Minsoo

2010-01-01

Intracellular signals associated with or triggered by integrin ligation can control cell survival, differentiation, proliferation, and migration. Despite accumulating evidence that conformational changes regulate integrin affinity to its ligands, how integrin structure regulates signal transmission from the outside to the inside of the cell remains elusive. Using fluorescence resonance energy transfer, we addressed whether conformational changes in integrin Mac-1 are sufficient to transmit outside-in signals in human neutrophils. Mac-1 conformational activation induced by ligand occupancy or activating Ab binding, but not integrin clustering, triggered similar patterns of intracellular protein tyrosine phosphorylation, including Akt phosphorylation, and inhibited spontaneous neutrophil apoptosis, indicating that global conformational changes are critical for Mac-1-dependent outside-in signal transduction. In neutrophils and myeloid K562 cells, ligand ICAM-1 or activating Ab binding promoted switchblade-like extension of the Mac-1 extracellular domain and separation of the αM and β2 subunit cytoplasmic tails, two structural hallmarks of integrin activation. These data suggest the primacy of global conformational changes in the generation of Mac-1 outside-in signals. PMID:19864611

Regulations for the transport of radioactive material in Italy: the role of the Italian Competent Authority (ANPA)

International Nuclear Information System (INIS)

Orsini, A.; Trivelloni, S.

1995-01-01

In Italy four Ministries, Industry, Transport, Marine Merchandise and Interior, have the legal responsibility to issue and apply the transport safety regulations for radioactive material. ANPA, the National Agency for Environmental Protection, has the technical duty to issue the approval certificates and to support the various Ministries in authorizing carriers for all modes of transport, in updating the regulations and advising in the case of emergency conditions. ANPA is monitoring the quantity of radioactive material transported in Italy, the radiation doses of workers and public, and verifying the implementation of transport regulations through inspections of the carriers and during storage in transit and handling. (Author)

Regulations for the transport of radioactive material in Italy: the role of the Italian Competent Authority (ANPA)

International Nuclear Information System (INIS)

Orsini, A.; Trivelloni, S.

1995-01-01

In Italy four Ministries, Industry, Transport, Marine Merchandise and Interior, have the legal responsibility to issue and apply the transport safety regulations for radioactive material. ANPA, the National Agency for Environmental Protection, has the technical duty to issue the approval certificates and to support the various Ministries in authorising carriers for all modes of transport, in updating the regulations and advising in the case of emergency conditions. ANPA is monitoring the quantity of radioactive material transported in Italy, the radiation doses of workers and public, and verifying the implementation of transport regulations through inspection of the carriers and during storage in transit and handling. (author)

The innovation inducement impact of environmental regulations on maritime transport

DEFF Research Database (Denmark)

Makkonen, Teemu; Repka, Sari

2016-01-01

, contrasting views, arguing that environmental regulations will, in fact, enhance firms’ competitiveness by inducing innovation, have also been voiced. Here this issue is examined through a literature review on the innovation inducement impact of environmental regulations (i.e. the Porter Hypothesis......), in general, and the economic impacts of environmental regulations (here Annex VI of the MARPOL Convention) as it applies to shipping in Northern Europe, in particular. According to the review, the literature is still inconclusive and lacks a clear consensus on the economic and innovation inducement impacts......Maritime transport is facing wide-ranking challenges due to stricter environmental regulations. It has been positioned that these stricter environmental regulations will significantly hamper the competitiveness of the shipping industry and other export/import oriented industries. However...

75 FR 38168 - Hazardous Materials: International Regulations for the Safe Transport of Radioactive Material (TS...

Science.gov (United States)

2010-07-01

... may also provide contact information, such as a telephone number and/or e-mail address. PHMSA and the.... PHMSA-2010-0130 (Notice No.10-2)] Hazardous Materials: International Regulations for the Safe Transport... (IAEA) ``Regulations for the Safe Transport of Radioactive Material'' (TS-R-1), which is scheduled for...

Decision from the Commission of Electricity Regulation (CRE) dated from December 12, 2002 about a disagreement between PEM Abrasif Refractaires (PEMAR) company and the Power transportation Network (RTE), as manager of the public power transportation grid, relative to the tariffing of public networks use applicable to the consumers connected in 42 kV voltage; Decision de la Commission de Regulation de l'Electricite (CRE) en date du 12 decembre 2002 sur un different qui oppose la societe PEM Abrasif Refractaires (PEMAR) a Reseau de Transport d'Electricite (RTE), en tant que gestionnaire du reseau public de transport d'electricite, relatif a la tarification d'utilisation des reseaux publics applicable aux consommateurs raccordes en tension 42 kV

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-12-01

This document presents the analysis made by the French commission of electricity regulation (CRE) about a high voltage tariff disagreement between PEM Abrasif Refractaires (PEMAR) company (La Defense, Courbevoie France) and RTE, the French manager of the power transportation grid. PEMAR company claims for a contract of power supply tariff conformable with the application of the decree from July 19, 2002 which, after comparison with the previous decrees, contains a mistake in the definition of voltage classes. (J.S.)

Schedules of Provisions of the IAEA Regulations for the Safe Transport of Radioactive Material (2009 Ed.). Safety Guide

International Nuclear Information System (INIS)

2014-01-01

This Safety Guide is issued in support of Regulations for the Safe Transport of Radioactive Material (IAEA Safety Standards Series No. TS-R-1, 2009 Edition). It lists the paragraph numbers of the Transport Regulations that are relevant for specified types of consignment, classified according to their UN numbers. It does not provide additional recommendations. The intended users are consignors and consignees, carriers, shippers, regulators, and end users involved in the transport of radioactive material. A person or organization intending to transport a particular type of consignment of radioactive material must meet requirements in all sections of the Transport Regulations. This Safety Guide aids users by providing a listing of the relevant requirements of the Transport Regulations for each type of radioactive material, package or shipment. Once a consignor has classified the radioactive material to be shipped, the appropriate UN number can be assigned and the paragraph numbers of the requirements that apply for the shipment can be found in the corresponding schedule

29 CFR 790.14 - “In conformity with.”

Science.gov (United States)

2010-07-01

... PORTAL-TO-PORTAL ACT OF 1947 ON THE FAIR LABOR STANDARDS ACT OF 1938 Defense of Good Faith Reliance on Administrative Regulations, Etc. § 790.14 “In conformity with.” (a) The “good faith” defense is not available to... previously pointed out, the opinion from the X Agency, if relied on and conformed with in good faith by the...

COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport

International Nuclear Information System (INIS)

Wang, Ying-Nai; Wang, Hongmei; Yamaguchi, Hirohito; Lee, Hong-Jen; Lee, Heng-Huan; Hung, Mien-Chie

2010-01-01

Research highlights: → ARF1 activation is involved in the EGFR transport to the ER and the nucleus. → Assembly of γ-COP coatomer mediates EGFR transport to the ER and the nucleus. → Golgi-to-ER retrograde trafficking regulates nuclear transport of EGFR. -- Abstract: Emerging evidence indicates that cell surface receptors, such as the entire epidermal growth factor receptor (EGFR) family, have been shown to localize in the nucleus. A retrograde route from the Golgi to the endoplasmic reticulum (ER) is postulated to be involved in the EGFR trafficking to the nucleus; however, the molecular mechanism in this proposed model remains unexplored. Here, we demonstrate that membrane-embedded vesicular trafficking is involved in the nuclear transport of EGFR. Confocal immunofluorescence reveals that in response to EGF, a portion of EGFR redistributes to the Golgi and the ER, where its NH 2 -terminus resides within the lumen of Golgi/ER and COOH-terminus is exposed to the cytoplasm. Blockage of the Golgi-to-ER retrograde trafficking by brefeldin A or dominant mutants of the small GTPase ADP-ribosylation factor, which both resulted in the disassembly of the coat protein complex I (COPI) coat to the Golgi, inhibit EGFR transport to the ER and the nucleus. We further find that EGF-dependent nuclear transport of EGFR is regulated by retrograde trafficking from the Golgi to the ER involving an association of EGFR with γ-COP, one of the subunits of the COPI coatomer. Our findings experimentally provide a comprehensive pathway that nuclear transport of EGFR is regulated by COPI-mediated vesicular trafficking from the Golgi to the ER, and may serve as a general mechanism in regulating the nuclear transport of other cell surface receptors.

Conformal field theory in conformal space

International Nuclear Information System (INIS)

Preitschopf, C.R.; Vasiliev, M.A.

1999-01-01

We present a new framework for a Lagrangian description of conformal field theories in various dimensions based on a local version of d + 2-dimensional conformal space. The results include a true gauge theory of conformal gravity in d = (1, 3) and any standard matter coupled to it. An important feature is the automatic derivation of the conformal gravity constraints, which are necessary for the analysis of the matter systems

Regulation of transepithelial transport of iron by hepcidin

Directory of Open Access Journals (Sweden)

NATALIA P MENA

2006-01-01

Full Text Available Hepcidin (Hepc is a 25 amino acid cationic peptide with broad antibacterial and antifungal actions. A likely role for Hepc in iron metabolism was suggested by the observation that mice having disruption of the gene encoding the transcription factor USF2 failed to produce Hepc mRNA and developed spontaneous visceral iron overload. Lately, Hepc has been considered the "stores regulator," a putative factor that signals the iron content of the body to intestinal cells. In this work, we characterized the effect of Hepc produced by hepatoma cells on iron absorption by intestinal cells. To that end, human Hepc cDNA was cloned and overexpressed in HepG2 cells and conditioned media from Hepc-overexpressing cells was used to study the effects of Hepc on intestinal Caco-2 cells grown in bicameral inserts. The results indicate that Hepc released by HepG2 inhibited apical iron uptake by Caco-2 cells, probably by inhibiting the expression of the apical transporter DMT1. These results support a model in which Hepc released by the liver negatively regulates the expression of transporter DMT1 in the enterocyte

75 FR 20922 - Approval and Promulgation of Air Quality Implementation Plans; New Mexico; Transportation...

Science.gov (United States)

2010-04-22

... with the January 2009, ``Guidance for Developing Transportation Conformity State Implementation Plans... Promulgation of Air Quality Implementation Plans; New Mexico; Transportation Conformity Requirement for... Transportation Conformity? II. What Is the Background for This Action? III. What Did the State Submit and How Did...

Determination of detailed regulations concerning transportation of radioactive materials by vehicles

International Nuclear Information System (INIS)

1978-01-01

These provisions are established on the basis of the ''Regulations concerning transportation of radioactive materials by vehicles''. The terms used hereinafter are according to those used in the Regulations. Radioactive materials include uranium 233, uranium 235, plutonium 238, plutonium 239, plutonium 241, the compounds of such materials and the substances containing one or two and more of such materials, excluding the radioactive materials with not more than 15 grams of such uranium and plutonium. The permissible surface density is 1/100,000 microcurie per cm 2 for radioactive materials emitting alpha-ray and 1/10,000 microcurie per cm 2 for such materials which does not emit alpha-ray. For the radioactive materials which can be transported as L type loads, their kinds and quantities are specified in the forms of solid, liquid and gas, respectively. Transporting conditions including the quantity and leakage in A, BM and BU type loads are provided for, respectively, in the lists attached and in the particular sections. (Okada, K.)

PAK4 crystal structures suggest unusual kinase conformational movements.

Science.gov (United States)

Zhang, Eric Y; Ha, Byung Hak; Boggon, Titus J

2018-02-01

In order for protein kinases to exchange nucleotide they must open and close their catalytic cleft. These motions are associated with rotations of the N-lobe, predominantly around the 'hinge region'. We conducted an analysis of 28 crystal structures of the serine-threonine kinase, p21-activated kinase 4 (PAK4), including three newly determined structures in complex with staurosporine, FRAX486, and fasudil (HA-1077). We find an unusual motion between the N-lobe and C-lobe of PAK4 that manifests as a partial unwinding of helix αC. Principal component analysis of the crystal structures rationalizes these movements into three major states, and analysis of the kinase hydrophobic spines indicates concerted movements that create an accessible back pocket cavity. The conformational changes that we observe for PAK4 differ from previous descriptions of kinase motions, and although we observe these differences in crystal structures there is the possibility that the movements observed may suggest a diversity of kinase conformational changes associated with regulation. Protein kinases are key signaling proteins, and are important drug targets, therefore understanding their regulation is important for both basic research and clinical points of view. In this study, we observe unusual conformational 'hinging' for protein kinases. Hinging, the opening and closing of the kinase sub-domains to allow nucleotide binding and release, is critical for proper kinase regulation and for targeted drug discovery. We determine new crystal structures of PAK4, an important Rho-effector kinase, and conduct analyses of these and previously determined structures. We find that PAK4 crystal structures can be classified into specific conformational groups, and that these groups are associated with previously unobserved hinging motions and an unusual conformation for the kinase hydrophobic core. Our findings therefore indicate that there may be a diversity of kinase hinging motions, and that these may

Structures of closed and open conformations of dimeric human ATM

Science.gov (United States)

Baretić, Domagoj; Pollard, Hannah K.; Fisher, David I.; Johnson, Christopher M.; Santhanam, Balaji; Truman, Caroline M.; Kouba, Tomas; Fersht, Alan R.; Phillips, Christopher; Williams, Roger L.

2017-01-01

ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase–related protein kinase (PIKK) best known for its role in DNA damage response. ATM also functions in oxidative stress response, insulin signaling, and neurogenesis. Our electron cryomicroscopy (cryo-EM) suggests that human ATM is in a dynamic equilibrium between closed and open dimers. In the closed state, the PIKK regulatory domain blocks the peptide substrate–binding site, suggesting that this conformation may represent an inactive or basally active enzyme. The active site is held in this closed conformation by interaction with a long helical hairpin in the TRD3 (tetratricopeptide repeats domain 3) domain of the symmetry-related molecule. The open dimer has two protomers with only a limited contact interface, and it lacks the intermolecular interactions that block the peptide-binding site in the closed dimer. This suggests that the open conformation may be more active. The ATM structure shows the detailed topology of the regulator-interacting N-terminal helical solenoid. The ATM conformational dynamics shown by the structures represent an important step in understanding the enzyme regulation. PMID:28508083

Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase.

Directory of Open Access Journals (Sweden)

Kara R Barber

2017-02-01

Full Text Available Disruption of synapses underlies a plethora of neurodevelopmental and neurodegenerative disease. Presynaptic specialization called the active zone plays a critical role in the communication with postsynaptic neuron. While the role of many proteins at the active zones in synaptic communication is relatively well studied, very little is known about how these proteins are transported to the synapses. For example, are there distinct mechanisms for the transport of active zone components or are they all transported in the same transport vesicle? Is active zone protein transport regulated? In this report we show that overexpression of Par-1/MARK kinase, a protein whose misregulation has been implicated in Autism spectrum disorders (ASDs and neurodegenerative disorders, lead to a specific block in the transport of an active zone protein component- Bruchpilot at Drosophila neuromuscular junctions. Consistent with a block in axonal transport, we find a decrease in number of active zones and reduced neurotransmission in flies overexpressing Par-1 kinase. Interestingly, we find that Par-1 acts independently of Tau-one of the most well studied substrates of Par-1, revealing a presynaptic function for Par-1 that is independent of Tau. Thus, our study strongly suggests that there are distinct mechanisms that transport components of active zones and that they are tightly regulated.

Visualizing multistep elevator-like transitions of a nucleoside transporter.

Science.gov (United States)

Hirschi, Marscha; Johnson, Zachary Lee; Lee, Seok-Yong

2017-05-04

Membrane transporters move substrates across the membrane by alternating access of their binding sites between the opposite sides of the membrane. An emerging model of this process is the elevator mechanism, in which a substrate-binding transport domain moves a large distance across the membrane. This mechanism has been characterized by a transition between two states, but the conformational path that leads to the transition is not yet known, largely because the available structural information has been limited to the two end states. Here we present crystal structures of the inward-facing, intermediate, and outward-facing states of a concentrative nucleoside transporter from Neisseria wadsworthii. Notably, we determined the structures of multiple intermediate conformations, in which the transport domain is captured halfway through its elevator motion. Our structures present a trajectory of the conformational transition in the elevator model, revealing multiple intermediate steps and state-dependent conformational changes within the transport domain that are associated with the elevator-like motion.

The effect of proposed changes to the IAEA transport regulations on decommissioning and other low level waste transportation

International Nuclear Information System (INIS)

Shetler, A.P.; Jayawardene, N.

1986-01-01

Ontario Hydro has studied the proposed changes to the IAEA Transport Regulations contained in the 1985 4th draft edition. The study shows that these proposed changes will have significant strategic and economic effects on the transportation of radioactive decommissioning and other low-level wastes. Under the 1985 4th draft edition, the definition of Low Specific Activity (LSA) material is revised and a new regulation is proposed which restricts the quantity of LSA material or Surface Contaminated Object (SCO) in a single package to that which would have an unshielded dose rate of 10 mSv/h (1 rem/h) at 3 m. The objective of this paper is to highlight the implications of the proposed regulatory changes. An example of the impact of these changes is presented by considering the transportation of typical CANDU decommissioning wastes which arise through piece-by-piece removal of a reactor assembly. The potential effect of the changes is that less decommissioning waste can be shipped in a single low-level waste package. This results in the requirement for so many small, low-level waste packages that Type B shipments are strategically and economically more attractive. However, use of Type B shipments would also result in higher dose uptake and waste management costs than under the 1973 Regulations

Transports of radioactive materials. Legal regulations, safety and security concepts, experience

International Nuclear Information System (INIS)

Schwarz, Guenther

2012-01-01

In Germany, approximately 650,000 to 750,000 units containing radioactive materials for scientific, medical and technical applications are shipped annually by surface, air and water transports. Legally speaking, radioactive materials are dangerous goods which can cause hazards to life, health, property and the environment as a result of faulty handling or accidents in transit. For protection against these hazards, their shipment therefore is regulated in extensive national and international rules of protection and safety. The article contains a topical review of the international and national transport regulations and codes pertaining to shipments of radioactive materials, and of the protection concepts underlying these codes so as to ensure an adequate standard of safety and security in shipping radioactive materials in national and international goods traffic. (orig.)

Relevant documents to IAEA regulations for the safe transport of radioactive materials

International Nuclear Information System (INIS)

El-Shinawy, R.M.K.; Sabek, M.G.; Gomma, M.

1998-01-01

IAEA regulations for the safe transport of radioactive materials provide standards for insuring a high level of safety of people, property, and environment against radiation, contamination, and criticality hazards as well as thermal effects associated with the transport of radioactive materials. IAEA routinely publishes technical reports which are relevant to radioactive material transportation such as INTERTRAN, directory of transport packaging test facilities, and others. A case study was performed to assess the impact of transporting radioactive materials through the suez canal using the two computer codes namely INTERTRAN and RADTRAN-4 which are part of IAEA technical documents. A comparison of the results of these two codes is given

α-Tubulin Tyrosination and CLIP-170 Phosphorylation Regulate the Initiation of Dynein-Driven Transport in Neurons

Directory of Open Access Journals (Sweden)

Jeffrey J. Nirschl

2016-03-01

Full Text Available Motor-cargo recruitment to microtubules is often the rate-limiting step of intracellular transport, and defects in this recruitment can cause neurodegenerative disease. Here, we use in vitro reconstitution assays with single-molecule resolution, live-cell transport assays in primary neurons, computational image analysis, and computer simulations to investigate the factors regulating retrograde transport initiation in the distal axon. We find that phosphorylation of the cytoskeletal-organelle linker protein CLIP-170 and post-translational modifications of the microtubule track combine to precisely control the initiation of retrograde transport. Computer simulations of organelle dynamics in the distal axon indicate that while CLIP-170 primarily regulates the time to microtubule encounter, the tyrosination state of the microtubule lattice regulates the likelihood of binding. These mechanisms interact to control transport initiation in the axon in a manner sensitive to the specialized cytoskeletal architecture of the neuron.

78 FR 36723 - Federal Management Regulation (FMR); Restrictions on International Transportation of Freight and...

Science.gov (United States)

2013-06-19

..., Sequence 1] RIN 3090-AJ34 Federal Management Regulation (FMR); Restrictions on International Transportation... Administration (GSA). ACTION: Proposed rule. SUMMARY: GSA is proposing to amend the Federal Management Regulation... Federal Management Regulation (FMR) to state clearly that this part applies to all agencies and wholly...

77 FR 36932 - Transportation of Household Goods in Interstate Commerce; Consumer Protection Regulations

Science.gov (United States)

2012-06-20

... use of energy. List of Subjects in 49 CFR Part 375 Advertising, Arbitration, Consumer protection...--TRANSPORTATION OF HOUSEHOLD GOODS IN INTERSTATE COMMERCE; CONSUMER PROTECTION REGULATIONS 0 1. The authority... No. FMCSA-2012-0119] RIN 2126-AB52 Transportation of Household Goods in Interstate Commerce; Consumer...

49 CFR 591.8 - Conformance bond and conditions.

Science.gov (United States)

2010-10-01

... SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) IMPORTATION OF VEHICLES AND EQUIPMENT SUBJECT TO FEDERAL SAFETY, BUMPER AND THEFT PREVENTION STANDARDS § 591.8 Conformance bond and conditions. (a) The bond required under section 591.6(c) for importation of a vehicle not originally manufactured...

77 FR 35671 - Conformed Power Marketing Criteria or Regulations for the Boulder Canyon Project

Science.gov (United States)

2012-06-14

... Interior or authorized representatives; applicable laws; the general terms, conditions, and principles contained in these 2012 Conformed Criteria; and the General Power Contract Provisions in effect. Long-term... (DOE), is modifying Part C of its Conformed General Consolidated Power Marketing Criteria or...

Rate and Regulation of Copper Transport by Human Copper Transporter 1 (hCTR1)*

Science.gov (United States)

Maryon, Edward B.; Molloy, Shannon A.; Ivy, Kristin; Yu, Huijun; Kaplan, Jack H.

2013-01-01

Human copper transporter 1 (hCTR1) is a homotrimer of a 190-amino acid monomer having three transmembrane domains believed to form a pore for copper permeation through the plasma membrane. The hCTR1-mediated copper transport mechanism is not well understood, nor has any measurement been made of the rate at which copper ions are transported by hCTR1. In this study, we estimated the rate of copper transport by the hCTR1 trimer in cultured cells using 64Cu uptake assays and quantification of plasma membrane hCTR1. For endogenous hCTR1, we estimated a turnover number of about 10 ions/trimer/s. When overexpressed in HEK293 cells, a second transmembrane domain mutant of hCTR1 (H139R) had a 3-fold higher Km value and a 4-fold higher turnover number than WT. Truncations of the intracellular C-terminal tail and an AAA substitution of the putative metal-binding HCH C-terminal tripeptide (thought to be required for transport) also exhibited elevated transport rates and Km values when compared with WT hCTR1. Unlike WT hCTR1, H139R and the C-terminal mutants did not undergo regulatory endocytosis in elevated copper. hCTR1 mutants combining methionine substitutions that block transport (M150L,M154L) on the extracellular side of the pore and the high transport H139R or AAA intracellular side mutations exhibited the blocked transport of M150L,M154L, confirming that Cu+ first interacts with the methionines during permeation. Our results show that hCTR1 elements on the intracellular side of the hCTR1 pore, including the carboxyl tail, are not essential for permeation, but serve to regulate the rate of copper entry. PMID:23658018

Residues in the extracellular loop 4 are critical for maintaining the conformational equilibrium of the gamma-aminobutyric acid transporter-1

DEFF Research Database (Denmark)

MacAulay, Nanna; Meinild, Anne-Kristine; Zeuthen, Thomas

2003-01-01

. Oocytes expressing M345H showed a decrease in apparent GABA affinity, an increase in apparent affinity for Na+, a shift in the charge/voltage (Q/Vm) relationship to more positive membrane potentials, and an increased Li+-induced leak current. Oocytes expressing T349H showed an increase in apparent GABA...... affinity, a decrease in apparent Na+ affinity, a profound shift in the Q/Vm relationship to more negative potentials, and a decreased Li+-induced leak current. The data are consistent with a shift in the conformational equilibrium of the mutant transporters, with M345H stabilized in an outward...

Fostering member state implementation of the IAEA's transport regulations

Energy Technology Data Exchange (ETDEWEB)

Brittinger, M.T.M.; Wangler, M.E. [International Atomic Energy Agency, Vienna (Austria)

2004-07-01

Based on a 1959 mandate from the United Nations Economic and Social Council, international safety requirements are embodied in the ''Regulations for the Safe Transport of Radioactive Material'' that were first published by the International Atomic Energy Agency in 1961 and revised in 1967, 1973, 1985 and 1996 to keep them abreast of scientific and technical developments. The requirements are incorporated into the regulatory documents of the International Civil Aviation Organization for air transport, and the International Maritime Organization for marine transport. As the requirements of the latter documents are legally-binding for the member states of the corresponding organizations, the IAEA safety requirements thus also become mandatory in those countries. The same situation applies for the surface modes in Europe, by means of the regulatory documents of the European Community for rail, road and inland waterways. Nevertheless, the IAEA has not relaxed its efforts to ensure that its Transport Regulations stay abreast of scientific and technical developments; on the contrary, it has been undertaking a regular and vigorous review of its safety requirements, and continues to do so with the assistance of Member States and relevant international organizations. Beyond providing the regulatory basis for the safe transport of radioactive material, however, the IAEA also offers a work programme under which it assists Member States in complying with the regulatory requirements. This assistance comes in the form of providing training on the safety requirements, and publishing documents that facilitate the exchange of information.

ATP and MO25alpha regulate the conformational state of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor.

Directory of Open Access Journals (Sweden)

Elton Zeqiraj

2009-06-01

Full Text Available Pseudokinases lack essential residues for kinase activity, yet are emerging as important regulators of signal transduction networks. The pseudokinase STRAD activates the LKB1 tumour suppressor by forming a heterotrimeric complex with LKB1 and the scaffolding protein MO25. Here, we describe the structure of STRADalpha in complex with MO25alpha. The structure reveals an intricate web of interactions between STRADalpha and MO25alpha involving the alphaC-helix of STRADalpha, reminiscent of the mechanism by which CDK2 interacts with cyclin A. Surprisingly, STRADalpha binds ATP and displays a closed conformation and an ordered activation loop, typical of active protein kinases. Inactivity is accounted for by nonconservative substitution of almost all essential catalytic residues. We demonstrate that binding of ATP enhances the affinity of STRADalpha for MO25alpha, and conversely, binding of MO25alpha promotes interaction of STRADalpha with ATP. Mutagenesis studies reveal that association of STRADalpha with either ATP or MO25alpha is essential for LKB1 activation. We conclude that ATP and MO25alpha cooperate to maintain STRADalpha in an "active" closed conformation required for LKB1 activation. It has recently been demonstrated that a mutation in human STRADalpha that truncates a C-terminal region of the pseudokinase domain leads to the polyhydramnios, megalencephaly, symptomatic epilepsy (PMSE syndrome. We demonstrate this mutation destabilizes STRADalpha and prevents association with LKB1. In summary, our findings describe one of the first structures of a genuinely inactive pseudokinase. The ability of STRADalpha to activate LKB1 is dependent on a closed "active" conformation, aided by ATP and MO25alpha binding. Thus, the function of STRADalpha is mediated through an active kinase conformation rather than kinase activity. It is possible that other pseudokinases exert their function through nucleotide binding and active conformations.

Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport

Directory of Open Access Journals (Sweden)

Nobuhiko Satoh

2015-01-01

Full Text Available A serine/threonine kinase Akt is a key mediator in various signaling pathways including regulation of renal tubular transport. In proximal tubules, Akt mediates insulin signaling via insulin receptor substrate 2 (IRS2 and stimulates sodium-bicarbonate cotransporter (NBCe1, resulting in increased sodium reabsorption. In insulin resistance, the IRS2 in kidney cortex is exceptionally preserved and may mediate the stimulatory effect of insulin on NBCe1 to cause hypertension in diabetes via sodium retention. Likewise, in distal convoluted tubules and cortical collecting ducts, insulin-induced Akt phosphorylation mediates several hormonal signals to enhance sodium-chloride cotransporter (NCC and epithelial sodium channel (ENaC activities, resulting in increased sodium reabsorption. Serum- and glucocorticoid-inducible kinase 1 (SGK1 mediates aldosterone signaling. Insulin can stimulate SGK1 to exert various effects on renal transporters. In renal cortical collecting ducts, SGK1 regulates the expression level of ENaC through inhibition of its degradation. In addition, SGK1 and Akt cooperatively regulate potassium secretion by renal outer medullary potassium channel (ROMK. Moreover, sodium-proton exchanger 3 (NHE3 in proximal tubules is possibly activated by SGK1. This review focuses on recent advances in understanding of the roles of Akt and SGK1 in the regulation of renal tubular transport.

Conformance and Deviance

DEFF Research Database (Denmark)

Gjerdrum Pedersen, Esben Rahbek; Neergaard, Peter; Thusgaard Pedersen, Janni

2013-01-01

This paper analyses how large Danish companies are responding to new governmental regulation which requires them to report on corporate social responsibility (CSR). The paper is based on an analysis of 142 company annual reports required by the new Danish regulation regarding CSR reporting, plus 10...... interviews with first-time reporting companies and six interviews with companies that failed to comply with the new law. It is concluded that coercive pressures from government have an impact on CSR reporting practices. Further, the analysis finds traces of mimetic isomorphism which inspires a homogenisation...... in CSR reporting practices. Finally, it is argued that non-conformance with the new regulatory requirements is not solely about conscious resistance but may also be caused by, for example, lack of awareness, resource limitations, misinterpretations, and practical difficulties....

48 CFR 227.7203-14 - Conformity, acceptance, and warranty of computer software and computer software documentation.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Conformity, acceptance... Software Documentation 227.7203-14 Conformity, acceptance, and warranty of computer software and computer...) Conformity and acceptance. Solicitations and contracts requiring the delivery of computer software shall...

Conformational Dynamics of apo-GlnBP Revealed by Experimental and Computational Analysis

KAUST Repository

Feng, Yitao

2016-10-13

The glutamine binding protein (GlnBP) binds l-glutamine and cooperates with its cognate transporters during glutamine uptake. Crystal structure analysis has revealed an open and a closed conformation for apo- and holo-GlnBP, respectively. However, the detailed conformational dynamics have remained unclear. Herein, we combined NMR spectroscopy, MD simulations, and single-molecule FRET techniques to decipher the conformational dynamics of apo-GlnBP. The NMR residual dipolar couplings of apo-GlnBP were in good agreement with a MD-derived structure ensemble consisting of four metastable states. The open and closed conformations are the two major states. This four-state model was further validated by smFRET experiments and suggests the conformational selection mechanism in ligand recognition of GlnBP. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Conformational Dynamics of apo-GlnBP Revealed by Experimental and Computational Analysis

KAUST Repository

Feng, Yitao; Zhang, Lu; Wu, Shaowen; Liu, Zhijun; Gao, Xin; Zhang, Xu; Liu, Maili; Liu, Jianwei; Huang, Xuhui; Wang, Wenning

2016-01-01

The glutamine binding protein (GlnBP) binds l-glutamine and cooperates with its cognate transporters during glutamine uptake. Crystal structure analysis has revealed an open and a closed conformation for apo- and holo-GlnBP, respectively. However, the detailed conformational dynamics have remained unclear. Herein, we combined NMR spectroscopy, MD simulations, and single-molecule FRET techniques to decipher the conformational dynamics of apo-GlnBP. The NMR residual dipolar couplings of apo-GlnBP were in good agreement with a MD-derived structure ensemble consisting of four metastable states. The open and closed conformations are the two major states. This four-state model was further validated by smFRET experiments and suggests the conformational selection mechanism in ligand recognition of GlnBP. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Conformational stabilization of the membrane embedded targeting domain of the lysosomal peptide transporter TAPL for solution NMR

Energy Technology Data Exchange (ETDEWEB)

Tumulka, Franz [Goethe-University Frankfurt, Institute of Biochemistry, Biocenter (Germany); Roos, Christian; Loehr, Frank [Goethe-University Frankfurt, Institute of Biophysical Chemistry, Biocenter (Germany); Bock, Christoph [Goethe-University Frankfurt, Institute of Biochemistry, Biocenter (Germany); Bernhard, Frank; Doetsch, Volker [Goethe-University Frankfurt, Institute of Biophysical Chemistry, Biocenter (Germany); Abele, Rupert, E-mail: abele@em.uni-frankfurt.de [Goethe-University Frankfurt, Institute of Biochemistry, Biocenter (Germany)

2013-10-15

The ATP binding cassette transporter TAPL translocates cytosolic peptides into the lumen of lysosomes driven by the hydrolysis of ATP. Functionally, this transporter can be divided into coreTAPL, comprising the transport function, and an additional N-terminal transmembrane domain called TMD0, which is essential for lysosomal targeting and mediates the interaction with the lysosomal associated membrane proteins LAMP-1 and LAMP-2. To elucidate the structure of this unique domain, we developed protocols for the production of high quantities of cell-free expressed TMD0 by screening different N-terminal expression tags. Independently of the amino acid sequence, high expression was detected for AU-rich sequences in the first seven codons, decreasing the free energy of RNA secondary structure formation at translation initiation. Furthermore, avoiding NGG codons in the region of translation initiation demonstrated a positive effect on expression. For NMR studies, conditions were optimized for high solubilization efficiency, long-term stability, and high quality spectra. A most critical step was the careful exchange of the detergent used for solubilization by the detergent dihexanoylphosphatidylcholine. Several constructs of different size were tested in order to stabilize the fold of TMD0 as well as to reduce the conformation exchange. NMR spectra with sufficient resolution and homogeneity were finally obtained with a TMD0 derivative only modified by a C-terminal His{sub 10}-tag and containing a codon optimized AT-rich sequence.

Application of United States Department of Transportation regulations to hazardous material and waste shipments on the Hanford site

International Nuclear Information System (INIS)

Burnside, M.E.

1992-01-01

All hazardous material and waste transported over roadways open to the public must be in compliance with the U.S. Department of Transportation (DOT) regulations. The DOT states that the hazardous material regulations (HMR) also apply to government-owned, contractor-operated (GOCO) transportation operations over any U.S. Department of Energy (DOE) site roadway where the public has free and unrestricted access. Hazardous material and waste in packages that do not meet DOT regulations must be transported on DOE site roadways in a manner that excludes the public and nonessential workers. At the DOE Richland Field Office (the Hanford Site), hazardous material and waste movements that do not meet DOT requirements are transported over public access roadways during off-peak hours with the roadways barricaded. These movements are accomplished using a transportation plan that involves the DOE, DOE contractors, and private utilities who operate on or near the Hanford Site. This method, which is used at the Hanford Site to comply with DOT regulations onsite, can be communicated to other DOE sites to provide a basis for achieving consistency in similar transportation operations. (author)

Radioactive Ores and Concentrates (Packaging and Transport) Regulations 1980 (Northern Territory) No. 30 of 21 July 1980

International Nuclear Information System (INIS)

1980-01-01

These Regulations were issued pursuant to the provisions of the 1980 Radioactive Ores and Concentrates (Packaging and Transport) Act. The primary purpose of the Regulations is to lay down specific record-keeping practices for persons licensed to transport and store radioactive material. (NEA) [fr

Regulations for the safe transport of radioactive material. 1985 ed. (As amended 1990)

International Nuclear Information System (INIS)

1990-01-01

This publication is an updated version of the 1985 Edition of the Transport Regulations and replaces all previous publications of IAEA Safety Series No. 6. It includes the Supplements 1986 and 1988 to the Regulations, the minor changes adopted by the Review Panel meeting which convened in Vienna, 10-14 July 1989, and also the changes of detail which survived the ''ninety day rule'' procedure which authorizes the Director General of the IAEA to promulgate such changes after giving Member States not less than ninety days notice and taking into account any comments they make. Since this publication is an updated version of the 1985 Edition of the Transport Regulations, the old IAEA Safety Series style is maintained for the convenience of the user, although the old style has now generally been superseded by a new one. It should be noted that subsequent editions of the Regulations will be published in the new style.

Quantifying polypeptide conformational space: sensitivity to conformation and ensemble definition.

Science.gov (United States)

Sullivan, David C; Lim, Carmay

2006-08-24

Quantifying the density of conformations over phase space (the conformational distribution) is needed to model important macromolecular processes such as protein folding. In this work, we quantify the conformational distribution for a simple polypeptide (N-mer polyalanine) using the cumulative distribution function (CDF), which gives the probability that two randomly selected conformations are separated by less than a "conformational" distance and whose inverse gives conformation counts as a function of conformational radius. An important finding is that the conformation counts obtained by the CDF inverse depend critically on the assignment of a conformation's distance span and the ensemble (e.g., unfolded state model): varying ensemble and conformation definition (1 --> 2 A) varies the CDF-based conformation counts for Ala(50) from 10(11) to 10(69). In particular, relatively short molecular dynamics (MD) relaxation of Ala(50)'s random-walk ensemble reduces the number of conformers from 10(55) to 10(14) (using a 1 A root-mean-square-deviation radius conformation definition) pointing to potential disconnections in comparing the results from simplified models of unfolded proteins with those from all-atom MD simulations. Explicit waters are found to roughen the landscape considerably. Under some common conformation definitions, the results herein provide (i) an upper limit to the number of accessible conformations that compose unfolded states of proteins, (ii) the optimal clustering radius/conformation radius for counting conformations for a given energy and solvent model, (iii) a means of comparing various studies, and (iv) an assessment of the applicability of random search in protein folding.

Interim guidance on the safe transport of uranium hexafluoride

International Nuclear Information System (INIS)

1991-06-01

Uranium hexafluoride (UF 6 ) is a radioactive material that has significant non-radiological hazardous properties. In conformity with international regulatory practice for dangerous goods transport, these properties are classed as ''subsidiary risks'', although they predominate in the cases of depleted and natural UF 6 . UF 6 is transported as a solid material below atmospheric pressure. The IAEA Regulations for the Safe Transport of Radioactive Material, 1985 Edition, Safety Series No. 6, make recommendations that aimed to provide an adequate level of safety against radiological and criticality hazards. The basis for these is that the stringency of package performance requirements, operational procedures and approval and administrative procedures is graded relative to the severity of the hazard. The cylinders used for transporting UF 6 are also used in the production, storage and use of the material and that the fraction of their life cycle in which transport is involved is small. Consideration must also be given to the large number of existing cylinders (estimated to be between 60,000 and 70,000). Specific recommendations provided for UF 6 transport, listed in Section II, are additional to the requirements of the Regulations. The intent of these additional recommendations is to restrict contamination and to provide protection to workers and to the general public against the chemical hazard possibly resulting from a severe accident involving the transport of UF 6 , and in addition against the consequences of explosive rupture of small bare cylinders of UF 6 . 20 refs, figs and tabs

Plastocyanin conformation: an analysis of its near ultraviolet absorption and circular dichroic spectra

International Nuclear Information System (INIS)

Draheim, J.E.; Anderson, G.P.; Duane, J.W.; Gross, E.L.

1986-01-01

The near-ultraviolet absorption and circular dichroic spectra of plastocyanin are dependent upon the redox state, solution pH, and ammonium sulfate concentration. This dependency was observed in plastocyanin isolated from spinach, poplar, and lettuce. Removal of the copper atom also perturbed the near-ultraviolet spectra. Upon reduction there are increases in both extinction and ellipticity at 252 nm. Further increases at 252 nm were observed upon formation of apo plastocyanin eliminating charge transfer transitions as the cause. The spectral changes in the near-ultraviolet imply a flexible tertiary conformation for plastocyanin. There are at least two charge transfer transitions at ∼295-340 nm. One of these transitions is sensitive to low pH's and is attributed to the His 87 copper ligand. The redox state dependent changes observed in the near-ultraviolet spectra of plastocyanin are attenuated either by decreasing the pH to 5 or by increasing the ammonium sulfate concentration to 2.7 M. This attenuation cannot be easily explained by simple charge screening. Hydrophobic interactions probably play an important role in this phenomenon. The pH and redox state dependent conformational changes may play an important role in regulating electron transport

75 FR 41994 - Federal Management Regulation; Home-to-Work Transportation

Science.gov (United States)

2010-07-20

..., Office of Governmentwide Policy, Office of Travel, Transportation, and Asset Management (MT), (202) 501.... Executive Order 12866 This final rule is excepted from the definition of ``regulation'' or ``rule'' under... approval of the Office of Management and Budget under 44 U.S.C. 3501, et seq. E. Small Business Regulatory...

Workers’ Conformism

Directory of Open Access Journals (Sweden)

Nikolay Ivantchev

2013-10-01

Full Text Available Conformism was studied among 46 workers with different kinds of occupations by means of two modified scales measuring conformity by Santor, Messervey, and Kusumakar (2000 – scale for perceived peer pressure and scale for conformism in antisocial situations. The hypothesis of the study that workers’ conformism is expressed in a medium degree was confirmed partly. More than a half of the workers conform in a medium degree for taking risk, and for the use of alcohol and drugs, and for sexual relationships. More than a half of the respondents conform in a small degree for anti-social activities (like a theft. The workers were more inclined to conform for risk taking (10.9%, then – for the use of alcohol, drugs and for sexual relationships (8.7%, and in the lowest degree – for anti-social activities (6.5%. The workers who were inclined for the use of alcohol and drugs tended also to conform for anti-social activities.

Dissecting the role of conformational change and membrane binding by the bacterial cell division regulator MinE in the stimulation of MinD ATPase activity.

Science.gov (United States)

Ayed, Saud H; Cloutier, Adam D; McLeod, Laura J; Foo, Alexander C Y; Damry, Adam M; Goto, Natalie K

2017-12-15

The bacterial cell division regulators MinD and MinE together with the division inhibitor MinC localize to the membrane in concentrated zones undergoing coordinated pole-to-pole oscillation to help ensure that the cytokinetic division septum forms only at the mid-cell position. This dynamic localization is driven by MinD-catalyzed ATP hydrolysis, stimulated by interactions with MinE's anti-MinCD domain. This domain is buried in the 6-β-stranded MinE "closed" structure, but is liberated for interactions with MinD, giving rise to a 4-β-stranded "open" structure through an unknown mechanism. Here we show that MinE-membrane interactions induce a structural change into a state resembling the open conformation. However, MinE mutants lacking the MinE membrane-targeting sequence stimulated higher ATP hydrolysis rates than the full-length protein, indicating that binding to MinD is sufficient to trigger this conformational transition in MinE. In contrast, conformational change between the open and closed states did not affect stimulation of ATP hydrolysis rates in the absence of membrane binding, although the MinD-binding residue Ile-25 is critical for this conformational transition. We therefore propose an updated model where MinE is brought to the membrane through interactions with MinD. After stimulation of ATP hydrolysis, MinE remains bound to the membrane in a state that does not catalyze additional rounds of ATP hydrolysis. Although the molecular basis for this inhibited state is unknown, previous observations of higher-order MinE self-association may explain this inhibition. Overall, our findings have general implications for Min protein oscillation cycles, including those that regulate cell division in bacterial pathogens. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Structure, Function and Regulation of the Hsp90 Machinery

Directory of Open Access Journals (Sweden)

Jing Li

2013-06-01

Full Text Available Heat shock protein 90 (Hsp90 is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.

Norepinephrine transporter function and desipramine: residual drug effects versus short-term regulation.

Science.gov (United States)

Ordway, Gregory A; Jia, Weihong; Li, Jing; Zhu, Meng-Yang; Mandela, Prashant; Pan, Jun

2005-04-30

Previous research has shown that exposure of norepinephrine transporter (NET)-expressing cells to desipramine (DMI) downregulates the norepinephrine transporter, although changes in the several transporter parameters do not demonstrate the same time course. Exposures to desipramine for effects of residual desipramine on norepinephrine transporter binding and uptake were re-evaluated following exposures of PC12 cells to desipramine using different methods to remove residual drug. Using a method that minimizes residual drug, exposure of intact PC12 cells to desipramine for 4h had no effect on uptake capacity or [(3)H]nisoxetine binding to the norepinephrine transporter, while exposures for > or =16 h reduced uptake capacity. Desipramine-induced reductions in binding to the transporter required >24 h or greater periods of desipramine exposure. This study confirms that uptake capacity of the norepinephrine transporter is reduced earlier than changes in radioligand binding, but with a different time course than originally shown. Special pre-incubation procedures are required to abolish effects of residual transporter inhibitor when studying inhibitor-induced transporter regulation.

Mechanism of Transport Modulation by an Extracellular Loop in an Archaeal Excitatory Amino Acid Transporter (EAAT) Homolog*

Science.gov (United States)

Mulligan, Christopher; Mindell, Joseph A.

2013-01-01

Secondary transporters in the excitatory amino acid transporter family terminate glutamatergic synaptic transmission by catalyzing Na+-dependent removal of glutamate from the synaptic cleft. Recent structural studies of the aspartate-specific archaeal homolog, GltPh, suggest that transport is achieved by a rigid body, piston-like movement of the transport domain, which houses the substrate-binding site, between the extracellular and cytoplasmic sides of the membrane. This transport domain is connected to an immobile scaffold by three loops, one of which, the 3–4 loop (3L4), undergoes substrate-sensitive conformational change. Proteolytic cleavage of the 3L4 was found to abolish transport activity indicating an essential function for this loop in the transport mechanism. Here, we demonstrate that despite the presence of fully cleaved 3L4, GltPh is still able to sample conformations relevant for transport. Optimized reconstitution conditions reveal that fully cleaved GltPh retains some transport activity. Analysis of the kinetics and temperature dependence of transport accompanied by direct measurements of substrate binding reveal that this decreased transport activity is not due to alteration of the substrate binding characteristics but is caused by the significantly reduced turnover rate. By measuring solute counterflow activity and cross-link formation rates, we demonstrate that cleaving 3L4 severely and specifically compromises one or more steps contributing to the movement of the substrate-loaded transport domain between the outward- and inward-facing conformational states, sparing the equivalent step(s) during the movement of the empty transport domain. These results reveal a hitherto unknown role for the 3L4 in modulating an essential step in the transport process. PMID:24155238

Conformation radiotherapy and conformal radiotherapy

International Nuclear Information System (INIS)

Morita, Kozo

1999-01-01

In order to coincide the high dose region to the target volume, the 'Conformation Radiotherapy Technique' using the multileaf collimator and the device for 'hollow-out technique' was developed by Prof. S. Takahashi in 1960. This technique can be classified a type of 2D-dynamic conformal RT techniques. By the clinical application of this technique, the late complications of the lens, the intestine and the urinary bladder after radiotherapy for the maxillary cancer and the cervical cancer decreased. Since 1980's the exact position and shape of the tumor and the surrounding normal tissues can be easily obtained by the tremendous development of the CT/MRI imaging technique. As a result, various kinds of new conformal techniques such as the 3D-CRT, the dose intensity modulation, the tomotherapy have been developed since the beginning of 1990'. Several 'dose escalation study with 2D-/3D conformal RT' is now under way to improve the treatment results. (author)

Transporad version 2.0 a software about the regulation of radioactive materials transports

International Nuclear Information System (INIS)

Bourgois, L.; Lelache, H.

1998-01-01

The software Transporad, version 2.0, founded on the decree on the fifth of December 1996 allows to know the regulations to apply, for the transport by road of the radioactive material. More-over, it allows to supply the transport documents. The computerized management allows to manage the traffic, the packaging stock, to edit accounting. (N.C.)

Self-regulation of turbulence bursts and transport barriers

International Nuclear Information System (INIS)

Floriani, E; Ciraolo, G; Ghendrih, Ph; Sarazin, Y; Lima, R

2013-01-01

The interplay between turbulent bursts and transport barriers is analyzed with a simplified model of interchange turbulence in magnetically confined plasmas. The turbulent bursts spread into the transport barriers and, depending on the competing magnitude of the burst and stopping capability of the barrier, can burn through. Simulations of two models of transport barriers are presented: a hard barrier where interchange turbulence modes are stable in a prescribed region and a soft barrier with external plasma biasing. The response of the transport barriers to the non-linear perturbations of the turbulent bursts, addressed in a predator–prey approach, indicates that the barriers monitor an amplification factor of the turbulent bursts, with amplification smaller than one for most bursts and, in some cases, amplification factors that can significantly exceed unity. The weak barriers in corrugated profiles and magnetic structures, as well as the standard barriers, are characterized by these transmission properties, which then regulate the turbulent burst transport properties. The interplays of barriers and turbulent bursts are modeled as competing stochastic processes. For different classes of the probability density function (PDF) of these processes, one can predict the heavy tail properties of the bursts downstream from the barrier, either exponential for a leaky barrier, or with power laws for a tight barrier. The intrinsic probing of the transport barriers by the turbulent bursts thus gives access to the properties of the barriers. The main stochastic variables are the barrier width and the spreading distance of the turbulent bursts within the barrier, together with their level of correlation. One finds that in the case of a barrier with volumetric losses, such as radiation or particle losses as addressed in our present simulations, the stochastic model predicts a leaky behavior with an exponential PDF of escaping turbulent bursts in agreement with the simulation

Explicit mentalizing mechanisms and their adaptive role in memory conformity.

Science.gov (United States)

Wheeler, Rebecca; Allan, Kevin; Tsivilis, Dimitris; Martin, Douglas; Gabbert, Fiona

2013-01-01

Memory conformity occurs when an individual endorses what other individuals remember about past events. Research on memory conformity is currently dominated by a 'forensic' perspective, which views the phenomenon as inherently undesirable. This is because conformity not only distorts the accuracy of an individual's memory, but also produces false corroboration between individuals, effects that act to undermine criminal justice systems. There is growing awareness, however, that memory conformity may be interpreted more generally as an adaptive social behavior regulated by explicit mentalizing mechanisms. Here, we provide novel evidence in support of this emerging alternative theoretical perspective. We carried out a memory conformity experiment which revealed that explicit belief-simulation (i.e. using one's own beliefs to model what other people believe) systematically biases conformity towards like-minded individuals, even when there is no objective evidence that they have a more accurate memory than dissimilar individuals. We suggest that this bias is functional, i.e. adaptive, to the extent that it fosters trust, and hence cooperation, between in-group versus out-group individuals. We conclude that memory conformity is, in more fundamental terms, a highly desirable product of explicit mentalizing mechanisms that promote adaptive forms of social learning and cooperation.

Killing tensors and conformal Killing tensors from conformal Killing vectors

International Nuclear Information System (INIS)

Rani, Raffaele; Edgar, S Brian; Barnes, Alan

2003-01-01

Koutras has proposed some methods to construct reducible proper conformal Killing tensors and Killing tensors (which are, in general, irreducible) when a pair of orthogonal conformal Killing vectors exist in a given space. We give the completely general result demonstrating that this severe restriction of orthogonality is unnecessary. In addition, we correct and extend some results concerning Killing tensors constructed from a single conformal Killing vector. A number of examples demonstrate that it is possible to construct a much larger class of reducible proper conformal Killing tensors and Killing tensors than permitted by the Koutras algorithms. In particular, by showing that all conformal Killing tensors are reducible in conformally flat spaces, we have a method of constructing all conformal Killing tensors, and hence all the Killing tensors (which will in general be irreducible) of conformally flat spaces using their conformal Killing vectors

Torsional Arming of Thiomannosyl Donors & Conformational Control of Hexahydropyridazines via pH

DEFF Research Database (Denmark)

Olsen, Jacob Ingemar

The overall objective of the research presented in this PhD thesis was to investigate torsional arming of thiogalacto- and thiomannosyl donors (part 1) and to investigate the possible synthesis and attachment of a pH regulated conformational switch to an α-cyclodextrin (part 2). Part 1: It is well...... demonstrated their ability to change conformation under different conditions. These conformational changes are connected to various intramolecular interactions and can to some extent, be controlled by pH (Chapter 3). Fusing these conformationally labile compounds to the rim of a cyclodextrin would create...... compounds that could release molecules at a specified change in pH conditions. To investigate this, four hexahydropyridazines were synthesized and investigated for their pH induced conformational change (Chapter 4). Out of the four compounds, one revealed to flip between two conformations depending on pH...

Structure-Function Relationship of Transporters in the Glutamate–Glutamine Cycle of the Central Nervous System

Directory of Open Access Journals (Sweden)

Mariko Kato Hayashi

2018-04-01

Full Text Available Many kinds of transporters contribute to glutamatergic excitatory synaptic transmission. Glutamate is loaded into synaptic vesicles by vesicular glutamate transporters to be released from presynaptic terminals. After synaptic vesicle release, glutamate is taken up by neurons or astrocytes to terminate the signal and to prepare for the next signal. Glutamate transporters on the plasma membrane are responsible for transporting glutamate from extracellular fluid to cytoplasm. Glutamate taken up by astrocyte is converted to glutamine by glutamine synthetase and transported back to neurons through glutamine transporters on the plasma membranes of the astrocytes and then on neurons. Glutamine is converted back to glutamate by glutaminase in the neuronal cytoplasm and then loaded into synaptic vesicles again. Here, the structures of glutamate transporters and glutamine transporters, their conformational changes, and how they use electrochemical gradients of various ions for substrate transport are summarized. Pharmacological regulations of these transporters are also discussed.

Summary report on transportation of nuclear fuel materials in Japan : transportation infrastructure, threats identified in open literature, and physical protection regulations.

Energy Technology Data Exchange (ETDEWEB)

Cochran, John Russell; Ouchi, Yuichiro (Japan Atomic Energy Agency, Japan); Furaus, James Phillip; Marincel, Michelle K.

2008-03-01

This report summarizes the results of three detailed studies of the physical protection systems for the protection of nuclear materials transport in Japan, with an emphasis on the transportation of mixed oxide fuel materials1. The Japanese infrastructure for transporting nuclear fuel materials is addressed in the first section. The second section of this report presents a summary of baseline data from the open literature on the threats of sabotage and theft during the transport of nuclear fuel materials in Japan. The third section summarizes a review of current International Atomic Energy Agency, Japanese and United States guidelines and regulations concerning the physical protection for the transportation of nuclear fuel materials.

Regulation of human trophoblast GLUT1 glucose transporter by insulin-like growth factor I (IGF-I.

Directory of Open Access Journals (Sweden)

Marc U Baumann

Full Text Available Glucose transport to the fetus across the placenta takes place via glucose transporters in the opposing faces of the barrier layer, the microvillous and basal membranes of the syncytiotrophoblast. While basal membrane content of the GLUT1 glucose transporter appears to be the rate-limiting step in transplacental transport, the factors regulating transporter expression and activity are largely unknown. In view of the many studies showing an association between IGF-I and fetal growth, we investigated the effects of IGF-I on placental glucose transport and GLUT1 transporter expression. Treatment of BeWo choriocarcinoma cells with IGF-I increased cellular GLUT1 protein. There was increased basolateral (but not microvillous uptake of glucose and increased transepithelial transport of glucose across the BeWo monolayer. Primary syncytial cells treated with IGF-I also demonstrated an increase in GLUT1 protein. Term placental explants treated with IGF-I showed an increase in syncytial basal membrane GLUT1 but microvillous membrane GLUT1 was not affected. The placental dual perfusion model was used to assess the effects of fetally perfused IGF-I on transplacental glucose transport and syncytial GLUT1 content. In control perfusions there was a decrease in transplacental glucose transport over the course of the perfusion, whereas in tissues perfused with IGF-I through the fetal circulation there was no change. Syncytial basal membranes from IGF-I perfused tissues showed an increase in GLUT1 content. These results demonstrate that IGF-I, whether acting via microvillous or basal membrane receptors, increases the basal membrane content of GLUT1 and up-regulates basal membrane transport of glucose, leading to increased transepithelial glucose transport. These observations provide a partial explanation for the mechanism by which IGF-I controls nutrient supply in the regulation of fetal growth.

International cooperation for the development of consistent and stable transportation regulations to promote and enhance safety and security

International Nuclear Information System (INIS)

Strosnider, J.

2004-01-01

International commerce of radioactive materials crosses national boundaries, linking separate regulatory institutions with a common purpose and making it necessary for these institutions to work together in order to achieve common safety goals in a manner that does not place an undue burden on industry and commerce. Widespread and increasing use of radioactive materials across the world has led to increases in the transport of radioactive materials. The demand for consistency in the oversight of international transport has also increased to prevent unnecessary delays and costs associated with incongruent or redundant regulatory requirements by the various countries through which radioactive material is transported. The International Atomic Energy Agency (IAEA) is the authority for international regulation of transportation of radioactive materials responsible for promulgation of regulations and guidance for the establishment of acceptable methods of transportation for the international community. As such, the IAEA is seen as the focal point for consensus building between its Member States to develop consistency in transportation regulations and reviews and to ensure the safe and secure transport of radioactive material. International cooperation is also needed to ensure stability in our regulatory processes. Changes to transportation regulations should be based on an anticipated safety benefit supported by risk information and insights gained from continuing experience, evaluation, and research studies. If we keep safety as the principle basis for regulatory changes, regulatory stability will be enhanced. Finally, as we endeavour to maintain consistency and stability in our international regulations, we must be mindful of the new security challenges that lay before the international community as a result of a changing terrorist environment. Terrorism is a problem of global concern that also requires international cooperation and support, as we look for ways to

The IAEA regulations for the safe transport of radioactive material; new strategies for the future

International Nuclear Information System (INIS)

Selling, H.A.; Brittinger, M.T.M.

1993-01-01

This paper presents a historic review of 30 years experience with the IAEA's Regulations for the Safe Transport of Radioactive Material as the basis for regulatory control of those materials worldwide. It is demonstrated that the underlying principles and fundamental philosophy have proven their validity and have been the main reason for the excellent safety record of transport operations. The IAEA Regulations are currently halfway a comprehensive revision process aiming at the publication of a new edition by 1996. Although the main principles are likely to be maintained in the next edition of the Regulations, some developments in this area will undoubtedly have an effect on their structure. The main new developments are: the air transport of large quantities of radioactive material, requiring that a risk basis be established which is comparable with other modes of transport, transport of uranium hexafluoride requiring provisions which include the associated chemical hazards, the transport of large volumes of radioactive waste originating from decommissioning of nuclear power stations, and the influence of the new risk estimates for exposure to ionizing radiation and consequently the lower dose limits as recommended by ICRP. This paper will make an attempt to identify the problems associated with those developments, to outline its programme of activities intended to address the problems and to suggest possible solutions as recommended by the IAEA senior advisory group in this subject area. (J.P.N.)

Replacement between conformity and counter-conformity in consumption decisions.

Science.gov (United States)

Chou, Ting-Jui; Chang, En-Chung; Dai, Qi; Wong, Veronica

2013-02-01

This study assessed, in a Chinese context, how self-esteem interacts with perceived similarity and uniqueness to yield cognitive dissonance, and whether the dissonance leads to self-reported conformity or counter-conformity behavior. Participants were 408 respondents from 4 major Chinese cities (M age = 33.0 yr., SD = 4.3; 48% men). Self-perceptions of uniqueness, similarity, cognitive dissonance, self-esteem and need to behave in conformity or counter-conformity were measured. A theoretical model was assessed in four situations, relating the ratings of self-esteem and perceived similarity/uniqueness to the way other people at a wedding were dressed, and the resultant cognitive dissonance and conformity/ counter-conformity behavior. Regardless of high or low self-esteem, all participants reported cognitive dissonance when they were told that they were dressed extremely similarly to or extremely differently from the other people attending the wedding. However, the conforming/counter-conforming strategies used by participants to resolve the cognitive dissonance differed. When encountering dissonance induced by the perceived extreme uniqueness of dress, participants with low self-esteem tended to say they would dress next time so as to conform with the way others were dressed, while those with high self-esteem indicated they would continue their counter-conformity in attire. When encountering dissonance induced by the perceived extreme similarity to others, both those with high and low self-esteem tended to say they would dress in an unorthodox manner to surprise other people in the future.

Regulation of dopamine transporter function by protein-protein interactions: new discoveries and methodological challenges

DEFF Research Database (Denmark)

Eriksen, Jacob; Jørgensen, Trine Nygaard; Gether, Ulrik

2010-01-01

-synaptic neurons. This has led to the identification of a plethora of different kinases, receptors and scaffolding proteins that interact with DAT and hereby either modulate the catalytic activity of the transporter or regulate its trafficking and degradation. Several new tools for studying DAT regulation in live...

Calcium-Mediated Regulation of Proton-Coupled Sodium Transport - Final Report

Energy Technology Data Exchange (ETDEWEB)

Schumaker, Karen S [Professor

2013-10-24

The long-term goal of our experiments was to understand mechanisms that regulate energy coupling by ion currents in plants. Activities of living organisms require chemical, mechanical, osmotic or electrical work, the energy for which is supplied by metabolism. Adenosine triphosphate (ATP) has long been recognized as the universal energy currency, with metabolism supporting the synthesis of ATP and the hydrolysis of ATP being used for the subsequent work. However, ATP is not the only energy currency in living organisms. A second and very different energy currency links metabolism to work by the movement of ions passing from one side of a membrane to the other. These ion currents play a major role in energy capture and they support a range of physiological processes from the active transport of nutrients to the spatial control of growth and development. In Arabidopsis thaliana (Arabidopsis), the activity of a plasma membrane Na+/H+ exchanger, SALT OVERLY SENSITIVE1 (SOS1), is essential for regulation of sodium ion homeostasis during plant growth in saline conditions. Mutations in SOS1 result in severely reduced seedling growth in the presence of salt compared to the growth of wild type. SOS1 is a secondary active transporter coupling movement of sodium ions out of the cell using energy stored in the transplasma membrane proton gradient, thereby preventing the build-up of toxic levels of sodium in the cytosol. SOS1 is regulated by complexes containing the SOS2 and CALCINEURIN B-LIKE10 (CBL10) or SOS3 proteins. CBL10 and SOS3 (also identified as CBL4) encode EF-hand calcium sensors that interact physically with and activate SOS2, a serine/threonine protein kinase. The CBL10/SOS2 or SOS3/SOS2 complexes then activate SOS1 Na+/H+ exchange activity. We completed our studies to understand how SOS1 activity is regulated. Specifically, we asked: (1) how does CBL10 regulate SOS1 activity? (2) What role do two putative CBL10-interacting proteins play in SOS1 regulation? (3) Are

Photosynthetic control of electron transport and the regulation of gene expression

NARCIS (Netherlands)

Foyer, C.H.; Neukermans, J.; Queval, G.; Noctor, G.; Harbinson, J.

2012-01-01

The term ‘photosynthetic control’ describes the short- and long-term mechanisms that regulate reactions in the photosynthetic electron transport (PET) chain so that the rate of production of ATP and NADPH is coordinated with the rate of their utilization in metabolism. At low irradiances these

ATP-induced conformational changes of nucleotide-binding domains in an ABC transporter. Importance of the water-mediated entropic force.

Science.gov (United States)

Hayashi, Tomohiko; Chiba, Shuntaro; Kaneta, Yusuke; Furuta, Tadaomi; Sakurai, Minoru

2014-11-06

ATP binding cassette (ABC) proteins belong to a superfamily of active transporters. Recent experimental and computational studies have shown that binding of ATP to the nucleotide binding domains (NBDs) of ABC proteins drives the dimerization of NBDs, which, in turn, causes large conformational changes within the transmembrane domains (TMDs). To elucidate the active substrate transport mechanism of ABC proteins, it is first necessary to understand how the NBD dimerization is driven by ATP binding. In this study, we selected MalKs (NBDs of a maltose transporter) as a representative NBD and calculated the free-energy change upon dimerization using molecular mechanics calculations combined with a statistical thermodynamic theory of liquids, as well as a method to calculate the translational, rotational, and vibrational entropy change. This combined method is applied to a large number of snapshot structures obtained from molecular dynamics simulations containing explicit water molecules. The results suggest that the NBD dimerization proceeds with a large gain of water entropy when ATP molecules bind to the NBDs. The energetic gain arising from direct NBD-NBD interactions is canceled by the dehydration penalty and the configurational-entropy loss. ATP hydrolysis induces a loss of the shape complementarity between the NBDs, which leads to the dissociation of the dimer, due to a decrease in the water-entropy gain and an increase in the configurational-entropy loss. This interpretation of the NBD dimerization mechanism in concert with ATP, especially focused on the water-mediated entropy force, is potentially applicable to a wide variety of the ABC transporters.

In Silico Analysis of the Regulation of the Photosynthetic Electron Transport Chain in C3 Plants.

Science.gov (United States)

Morales, Alejandro; Yin, Xinyou; Harbinson, Jeremy; Driever, Steven M; Molenaar, Jaap; Kramer, David M; Struik, Paul C

2018-02-01

We present a new simulation model of the reactions in the photosynthetic electron transport chain of C3 species. We show that including recent insights about the regulation of the thylakoid proton motive force, ATP/NADPH balancing mechanisms (cyclic and noncyclic alternative electron transport), and regulation of Rubisco activity leads to emergent behaviors that may affect the operation and regulation of photosynthesis under different dynamic environmental conditions. The model was parameterized with experimental results in the literature, with a focus on Arabidopsis ( Arabidopsis thaliana ). A dataset was constructed from multiple sources, including measurements of steady-state and dynamic gas exchange, chlorophyll fluorescence, and absorbance spectroscopy under different light intensities and CO 2 , to test predictions of the model under different experimental conditions. Simulations suggested that there are strong interactions between cyclic and noncyclic alternative electron transport and that an excess capacity for alternative electron transport is required to ensure adequate redox state and lumen pH. Furthermore, the model predicted that, under specific conditions, reduction of ferredoxin by plastoquinol is possible after a rapid increase in light intensity. Further analysis also revealed that the relationship between ATP synthesis and proton motive force was highly regulated by the concentrations of ATP, ADP, and inorganic phosphate, and this facilitated an increase in nonphotochemical quenching and proton motive force under conditions where metabolism was limiting, such as low CO 2 , high light intensity, or combined high CO 2 and high light intensity. The model may be used as an in silico platform for future research on the regulation of photosynthetic electron transport. © 2018 American Society of Plant Biologists. All Rights Reserved.

Elucidation of the glucose transport pathway in glucose transporter 4 via steered molecular dynamics simulations.

Directory of Open Access Journals (Sweden)

Aswathy Sheena

Full Text Available BACKGROUND: GLUT4 is a predominant insulin regulated glucose transporter expressed in major glucose disposal tissues such as adipocytes and muscles. Under the unstimulated state, GLUT4 resides within intracellular vesicles. Various stimuli such as insulin translocate this protein to the plasma membrane for glucose transport. In the absence of a crystal structure for GLUT4, very little is known about the mechanism of glucose transport by this protein. Earlier we proposed a homology model for GLUT4 and performed a conventional molecular dynamics study revealing the conformational rearrangements during glucose and ATP binding. However, this study could not explain the transport of glucose through the permeation tunnel. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the molecular mechanism of glucose transport and its energetic, a steered molecular dynamics study (SMD was used. Glucose was pulled from the extracellular end of GLUT4 to the cytoplasm along the pathway using constant velocity pulling method. We identified several key residues within the tunnel that interact directly with either the backbone ring or the hydroxyl groups of glucose. A rotation of glucose molecule was seen near the sugar binding site facilitating the sugar recognition process at the QLS binding site. CONCLUSIONS/SIGNIFICANCE: This study proposes a possible glucose transport pathway and aids the identification of several residues that make direct interactions with glucose during glucose transport. Mutational studies are required to further validate the observation made in this study.

The conformational dynamics of the mitochondrial Hsp70 chaperone.

Science.gov (United States)

Mapa, Koyeli; Sikor, Martin; Kudryavtsev, Volodymyr; Waegemann, Karin; Kalinin, Stanislav; Seidel, Claus A M; Neupert, Walter; Lamb, Don C; Mokranjac, Dejana

2010-04-09

Heat shock proteins 70 (Hsp70) represent a ubiquitous and conserved family of molecular chaperones involved in a plethora of cellular processes. The dynamics of their ATP hydrolysis-driven and cochaperone-regulated conformational cycle are poorly understood. We used fluorescence spectroscopy to analyze, in real time and at single-molecule resolution, the effects of nucleotides and cochaperones on the conformation of Ssc1, a mitochondrial member of the family. We report that the conformation of its ADP state is unexpectedly heterogeneous, in contrast to a uniform ATP state. Substrates are actively involved in determining the conformation of Ssc1. The J protein Mdj1 does not interact transiently with the chaperone, as generally believed, but rather is released slowly upon ATP hydrolysis. Analysis of the major bacterial Hsp70 revealed important differences between highly homologous members of the family, possibly explaining tuning of Hsp70 chaperones to meet specific functions in different organisms and cellular compartments. 2010 Elsevier Inc. All rights reserved.

Advisory group for the comprehensive review of the Agency's regulations for the safe transport of radioactive materials. Vienna, 1-12 September 1980

International Nuclear Information System (INIS)

Rawl, R.R.

1981-05-01

The discussions and recommendations for the revision of the IAEA regulations for the safe transport of radioactive materials are reported. The last revision of the regulations was published in 1973. The regulations have been adopted by all international bodies concerned with transport and by almost all individual Member States. In view of the developments in the means of transport, the volume of traffic and the nature of materials transported, Member States and international organizations rely on the Agency for advice and guidance. Hence the regulations are to be reviewed by 1983

Review of the bases for regulations governing the transport of fissile and other radioactive material

International Nuclear Information System (INIS)

Smith, D.R.; Thomas, J.T.

1978-01-01

The outstanding record of transport of radioactive materials prompted this brief review of the history of the regulations. IAEA as well as DOT regulations are discussed, as are all classes of shipments and materials (Class I, II, III)

75 FR 20591 - AES Sparrows Point LNG, LLC and Mid-Atlantic Express, LLC; Notice of Final General Conformity...

Science.gov (United States)

2010-04-20

...] AES Sparrows Point LNG, LLC and Mid-Atlantic Express, LLC; Notice of Final General Conformity... revised draft Final General Conformity Determination (GCD) for Pennsylvania to assess the potential air... the above-referenced dockets. In accordance with the General Conformity Regulations under the Code of...

Stress regulated members of the plant organic cation transporter family are localized to the vacuolar membrane

Directory of Open Access Journals (Sweden)

Koch Wolfgang

2008-07-01

Full Text Available Abstract Background In Arabidopsis six genes group into the gene family of the organic cation transporters (OCTs. In animals the members of the OCT-family are mostly characterized as polyspecific transporters involved in the homeostasis of solutes, the transport of monoamine neurotransmitters and the transport of choline and carnitine. In plants little is known about function, localisation and regulation of this gene family. Only one protein has been characterized as a carnitine transporter at the plasma membrane so far. Findings We localized the five uncharacterized members of the Arabidopsis OCT family, designated OCT2-OCT6, via GFP fusions and protoplast transformation to the tonoplast. Expression analysis with RNA Gel Blots showed a distinct, organ-specific expression pattern of the individual genes. With reporter gene fusion of four members we analyzed the tissue specific distribution of OCT2, 3, 4, and 6. In experiments with salt, drought and cold stress, we could show that AtOCT4, 5 and 6 are up-regulated during drought stress, AtOCT3 and 5 during cold stress and AtOCT 5 and 6 during salt stress treatments. Conclusion Localisation of the proteins at the tonoplast and regulation of the gene expression under stress conditions suggests a specific role for the transporters in plant adaptation to environmental stress.

Explicit mentalizing mechanisms and their adaptive role in memory conformity.

Directory of Open Access Journals (Sweden)

Rebecca Wheeler

Full Text Available Memory conformity occurs when an individual endorses what other individuals remember about past events. Research on memory conformity is currently dominated by a 'forensic' perspective, which views the phenomenon as inherently undesirable. This is because conformity not only distorts the accuracy of an individual's memory, but also produces false corroboration between individuals, effects that act to undermine criminal justice systems. There is growing awareness, however, that memory conformity may be interpreted more generally as an adaptive social behavior regulated by explicit mentalizing mechanisms. Here, we provide novel evidence in support of this emerging alternative theoretical perspective. We carried out a memory conformity experiment which revealed that explicit belief-simulation (i.e. using one's own beliefs to model what other people believe systematically biases conformity towards like-minded individuals, even when there is no objective evidence that they have a more accurate memory than dissimilar individuals. We suggest that this bias is functional, i.e. adaptive, to the extent that it fosters trust, and hence cooperation, between in-group versus out-group individuals. We conclude that memory conformity is, in more fundamental terms, a highly desirable product of explicit mentalizing mechanisms that promote adaptive forms of social learning and cooperation.

Regulation of ER-Golgi Transport Dynamics by GTPases in Budding Yeast

Directory of Open Access Journals (Sweden)

Yasuyuki Suda

2018-01-01

Full Text Available A large number of proteins are synthesized de novo in the endoplasmic reticulum (ER. They are transported through the Golgi apparatus and then delivered to their proper destinations. The ER and the Golgi play a central role in protein processing and sorting and show dynamic features in their forms. Ras super family small GTPases mediate the protein transport through and between these organelles. The ER-localized GTPase, Sar1, facilitates the formation of COPII transport carriers at the ER exit sites (ERES on the ER for the transport of cargo proteins from the ER to the Golgi. The Golgi-localized GTPase, Arf1, controls intra-Golgi, and Golgi-to-ER transport of cargo proteins by the formation of COPI carriers. Rab GTPases localized at the Golgi, which are responsible for fusion of membranes, are thought to establish the identities of compartments. Recent evidence suggests that these small GTPases regulate not only discrete sites for generation/fusion of transport carriers, but also membrane dynamics of the organelles where they locate to ensure the integrity of transport. Here we summarize the current understandings about the membrane traffic between these organelles and highlight the cutting-edge advances from super-resolution live imaging of budding yeast, Saccharomyces cerevisiae.

Membrane-traversing mechanism of thyroid hormone transport by monocarboxylate transporter 8.

Science.gov (United States)

Protze, Jonas; Braun, Doreen; Hinz, Katrin Manuela; Bayer-Kusch, Dorothea; Schweizer, Ulrich; Krause, Gerd

2017-06-01

Monocarboxylate transporter 8 (MCT8) mediates thyroid hormone (TH) transport across the plasma membrane in many cell types. In order to better understand its mechanism, we have generated three new MCT8 homology models based on sugar transporters XylE in the intracellular opened (PDB ID: 4aj4) and the extracellular partly occluded (PDB ID: 4gby) conformations as well as FucP (PDB ID: 3o7q) and GLUT3 (PDB ID: 4zwc) in the fully extracellular opened conformation. T 3 -docking studies from both sides revealed interactions with His192, His415, Arg445 and Asp498 as previously identified. Selected mutations revealed further transport-sensitive positions mainly at the discontinuous transmembrane helices TMH7 and 10. Lys418 is potentially involved in neutralising the charge of the TH substrate because it can be replaced by charged, but not by uncharged, amino acids. The side chain of Thr503 was hypothesised to stabilise a helix break at TMH10 that undergoes a prominent local shift during the transport cycle. A T503V mutation accordingly affected transport. The aromatic Tyr419, the polar Ser313 and Ser314 as well as the charged Glu422 and Glu423 lining the transport channel have been studied. Based on related sugar transporters, we suggest an alternating access mechanism for MCT8 involving a series of amino acid positions previously and newly identified as critical for transport.

Conformal Fabrication of Colloidal Quantum Dot Solids for Optically Enhanced Photovoltaics

KAUST Repository

Labelle, André J.

2015-05-26

© 2015 American Chemical Society. Colloidal quantum dots (CQD) are an attractive thin-film material for photovoltaic applications due to low material costs, ease of fabrication, and size-tunable band gap. Unfortunately, today they suffer from a compromise between light absorption and photocarrier extraction, a fact that currently prevents the complete harvest of incoming above-band-gap solar photons. We have investigated the use of structured substrates and/or electrodes to increase the effective light path through the active material and found that these designs require highly conformal application of the light-absorbing films to achieve the greatest enhancement. This conformality requirement derives from the need for maximal absorption enhancement combined with shortest-distance charge transport. Here we report on a means of processing highly conformal layer-by-layer deposited CQD absorber films onto microstructured, light-recycling electrodes. Specifically, we engineer surface hydrophilicity to achieve conformal deposition of upper layers atop underlying ones. We show that only with the application of conformal coating can we achieve optimal quantum efficiency and enhanced power conversion efficiency in structured-electrode CQD cells.

Conformal house

DEFF Research Database (Denmark)

Ryttov, Thomas Aaby; Sannino, Francesco

2010-01-01

fixed point. As a consistency check we recover the previously investigated bounds of the conformal windows when restricting to a single matter representation. The earlier conformal windows can be imagined to be part now of the new conformal house. We predict the nonperturbative anomalous dimensions...... at the infrared fixed points. We further investigate the effects of adding mass terms to the condensates on the conformal house chiral dynamics and construct the simplest instanton induced effective Lagrangian terms...

ICK is essential for cell type-specific ciliogenesis and the regulation of ciliary transport.

Science.gov (United States)

Chaya, Taro; Omori, Yoshihiro; Kuwahara, Ryusuke; Furukawa, Takahisa

2014-06-02

Cilia and flagella are formed and maintained by intraflagellar transport (IFT) and play important roles in sensing and moving across species. At the distal tip of the cilia/flagella, IFT complexes turn around to switch from anterograde to retrograde transport; however, the underlying regulatory mechanism is unclear. Here, we identified ICK localization at the tip of cilia as a regulator of ciliary transport. In ICK-deficient mice, we found ciliary defects in neuronal progenitor cells with Hedgehog signal defects. ICK-deficient cells formed cilia with mislocalized Hedgehog signaling components. Loss of ICK caused the accumulation of IFT-A, IFT-B, and BBSome components at the ciliary tips. In contrast, overexpression of ICK induced the strong accumulation of IFT-B, but not IFT-A or BBSome components at ciliary tips. In addition, ICK directly phosphorylated Kif3a, while inhibition of this Kif3a phosphorylation affected ciliary formation. Our results suggest that ICK is a Kif3a kinase and essential for proper ciliogenesis in development by regulating ciliary transport at the tip of cilia. © 2014 The Authors.

Arrangements for transition from the 1985 edition (as amended 1990) to the 1996 edition of the IAEA Transport Regulations

International Nuclear Information System (INIS)

2001-01-01

In December 1996 the International Atomic Energy Agency published the 1996 Edition of the Regulations for the Safe Transport of Radioactive Material (formerly Safety Series No. 6) in a document called ST-1. That document has served as the basis for revising the UN Committee of Experts Recommendations on the Safe Transport of Dangerous Goods (published in 1999 as ''Model Regulations''), and as the basis for the Class 7 portions of the forthcoming revisions of RID, ADR, IMO (IMDG Code), ICAO (Technical Instructions) and IATA modal dangerous goods regulations. ST-1 was subsequently reviewed and revised with minor editorial corrections, and in 2000, a revised English version of the regulations called TS-R-1 (ST-1, Revised) was published. Difficulties may arise when applying the Regulations during the transition from the 1985 Edition of the Transport Regulations to the 1996 Edition of these regulations. These difficulties come mainly from the differences between the two sets of regulations, e.g. the definition of radioactive material with the new nuclide specific exemption levels, the new values of A 1 /A 2 , the annual dose limits, the related documentation, the labelling requirements for fissile material package, the changes in UN numbers and proper shipping names, the shipment of fissile material by air, etc. This TECDOC is intended to provide guidance on the implementation of changes in the Regulations for the Safe Transport of Radioactive Material. This guidance may be used to facilitate compliance with the Regulations. This guidance is aimed at all users of the regulations including National Competent Authorities, consignors, consignees and carriers

Substrate-specific reorganization of the conformational ensemble of CSK implicates novel modes of kinase function.

Directory of Open Access Journals (Sweden)

Michael A Jamros

Full Text Available Protein kinases use ATP as a phosphoryl donor for the posttranslational modification of signaling targets. It is generally thought that the binding of this nucleotide induces conformational changes leading to closed, more compact forms of the kinase domain that ideally orient active-site residues for efficient catalysis. The kinase domain is oftentimes flanked by additional ligand binding domains that up- or down-regulate catalytic function. C-terminal Src kinase (Csk is a multidomain tyrosine kinase that is up-regulated by N-terminal SH2 and SH3 domains. Although the X-ray structure of Csk suggests the enzyme is compact, X-ray scattering studies indicate that the enzyme possesses both compact and open conformational forms in solution. Here, we investigated whether interactions with the ATP analog AMP-PNP and ADP can shift the conformational ensemble of Csk in solution using a combination of small angle x-ray scattering and molecular dynamics simulations. We find that binding of AMP-PNP shifts the ensemble towards more extended rather than more compact conformations. Binding of ADP further shifts the ensemble towards extended conformations, including highly extended conformations not adopted by the apo protein, nor by the AMP-PNP bound protein. These ensembles indicate that any compaction of the kinase domain induced by nucleotide binding does not extend to the overall multi-domain architecture. Instead, assembly of an ATP-bound kinase domain generates further extended forms of Csk that may have relevance for kinase scaffolding and Src regulation in the cell.

75 FR 24434 - Federal Travel Regulation (FTR); Transportation in Conjunction With Official Travel and Relocation

Science.gov (United States)

2010-05-05

...-0010, sequence 1] RIN 3090-AJ02 Federal Travel Regulation (FTR); Transportation in Conjunction With Official Travel and Relocation AGENCY: Office of Governmentwide Policy, General Services Administration (GSA). ACTION: Final rule. SUMMARY: This final rule amends the Federal Travel Regulation (FTR), by...

Regulations concerning the transport of nuclear fuel materials outside the works or the enterprise

International Nuclear Information System (INIS)

1979-01-01

The regulations are defined under the law for the regulations of nuclear source materials, nuclear fuel materials and reactors and the order for execution of the law. Basic concepts and terms are explained, such as: vehicle transport; easy transport; nuclear fuel material load, exclusive loading, employee, accumulative dose and exposure dose. Technical standards of vehicle transport are specified in detail on nucler fuel materials as nuclear fuel load, L,A, EM and BU type of load, nuclear fuel load of fission substances, the second and third type of fission load and materials contaminated by nuclear fuel substances to be carried not as nuclear fuel loads. Special exceptional measures to such transport and technical standards of easy transport are also designated. The application for confirmation of the transport shall be filed to the Director General of Science and Technology Agency according to the form attached with documents explaining nuclear fuel materials to be transferred, the vessel of such materials and construction, material and method of production of such a vessel, safety of nuclear materials contained, etc. Measures in dangerous situations shall be taken to fight a fire or prohibit the entrance of persons other than the staff concerned. Reports shall be presented in 10 days to the Director, when theft, loss or irregular leaking of nuclear fuel materials or personal troubles occur on the way. (Okada, K.)

p27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability

Directory of Open Access Journals (Sweden)

Giovanni Morelli

2018-05-01

Full Text Available Summary: The protein p27Kip1 plays roles that extend beyond cell-cycle regulation during cerebral cortex development, such as the regulation of neuronal migration and neurite branching via signaling pathways that converge on the actin and microtubule cytoskeletons. Microtubule-dependent transport is essential for the maturation of neurons and the establishment of neuronal connectivity though synapse formation and maintenance. Here, we show that p27Kip1 controls the transport of vesicles and organelles along the axon of mice cortical projection neurons in vitro. Moreover, suppression of the p27Kip1 ortholog, dacapo, in Drosophila melanogaster disrupts axonal transport in vivo, leading to the reduction of locomotor activity in third instar larvae and adult flies. At the molecular level, p27Kip1 stabilizes the α-tubulin acetyltransferase 1, thereby promoting the acetylation of microtubules, a post-translational modification required for proper axonal transport. : Morelli et al. report that p27Kip1/Dacapo modulates the acetylation of microtubules in axons via stabilization of ATAT1, the main α-tubulin acetyltransferase. Its conditional loss leads to the reduction of bidirectional axonal transport of vesicles and mitochondria in vitro in mice and in vivo in Drosophila. Keywords: p27Kip1, dacapo, acetylation, axonal transport, ATAT1, alpha-tubulin, HDAC6, Drosophila, mouse, cerebral cortex

Agp2, a Member of the Yeast Amino Acid Permease Family, Positively Regulates Polyamine Transport at the Transcriptional Level

KAUST Repository

Aouida, Mustapha

2013-06-03

Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3? nor sam3? single mutant is defective in polyamine transport, while the dur3? sam3? double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2? mutant. Studies of Agp2 localization indicate that in the double mutant dur3? sam3?, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport. © 2013 Aouida et al.

Agp2, a Member of the Yeast Amino Acid Permease Family, Positively Regulates Polyamine Transport at the Transcriptional Level

KAUST Repository

Aouida, Mustapha; Texeira, Marta Rubio; Thevelein, Johan M.; Poulin, Richard; Ramotar, Dindial

2013-01-01

Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3? nor sam3? single mutant is defective in polyamine transport, while the dur3? sam3? double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2? mutant. Studies of Agp2 localization indicate that in the double mutant dur3? sam3?, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport. © 2013 Aouida et al.

Molecular insight into conformational transmission of human P-glycoprotein

International Nuclear Information System (INIS)

Chang, Shan-Yan; Liu, Fu-Feng; Dong, Xiao-Yan; Sun, Yan

2013-01-01

P-glycoprotein (P-gp), a kind of ATP-binding cassette transporter, can export candidates through a channel at the two transmembrane domains (TMDs) across the cell membranes using the energy released from ATP hydrolysis at the two nucleotide-binding domains (NBDs). Considerable evidence has indicated that human P-gp undergoes large-scale conformational changes to export a wide variety of anti-cancer drugs out of the cancer cells. However, molecular mechanism of the conformational transmission of human P-gp from the NBDs to the TMDs is still unclear. Herein, targeted molecular dynamics simulations were performed to explore the atomic detail of the conformational transmission of human P-gp. It is confirmed that the conformational transition from the inward- to outward-facing is initiated by the movement of the NBDs. It is found that the two NBDs move both on the two directions (x and y). The movement on the x direction leads to the closure of the NBDs, while the movement on the y direction adjusts the conformations of the NBDs to form the correct ATP binding pockets. Six key segments (KSs) protruding from the TMDs to interact with the NBDs are identified. The relative movement of the KSs along the y axis driven by the NBDs can be transmitted through α-helices to the rest of the TMDs, rendering the TMDs to open towards periplasm in the outward-facing conformation. Twenty eight key residue pairs are identified to participate in the interaction network that contributes to the conformational transmission from the NBDs to the TMDs of human P-gp. In addition, 9 key residues in each NBD are also identified. The studies have thus provided clear insight into the conformational transmission from the NBDs to the TMDs in human P-gp

[Cloning and expression analysis of a zinc-regulated transporters (ZRT), iron-regulated transporter (IRT)-like protein encoding gene in Dendrobium officinale].

Science.gov (United States)

Zhang, Gang; Li, Yi-Min; Li, Biao; Zhang, Da-Wei; Guo, Shun-Xing

2015-01-01

The zinc-regulated transporters (ZRT), iron-regulated transporter (IRT)-like protein (ZIP) plays an important role in the growth and development of plant. In this study, a full length cDNA of ZIP encoding gene, designed as DoZIP1 (GenBank accession KJ946203), was identified from Dendrobium officinale using RT-PCR and RACE. Bioinformatics analysis showed that DoZIP1 consisted of a 1,056 bp open reading frame (ORF) encoded a 351-aa protein with a molecular weight of 37.57 kDa and an isoelectric point (pI) of 6.09. The deduced DoZIP1 protein contained the conserved ZIP domain, and its secondary structure was composed of 50.71% alpha helix, 11.11% extended strand, 36.18% random coil, and beta turn 1.99%. DoZIP1 protein exhibited a signal peptide and eight transmembrane domains, presumably locating in cell membrane. The amino acid sequence had high homology with ZIP proteins from Arabidopsis, alfalfa and rice. A phylogenetic tree analysis demonstrated that DoZIP1 was closely related to AtZIP10 and OsZIP3, and they were clustered into one clade. Real time quantitative PCR analysis demonstrated that the transcription level of DoZIP1 in D. officinale roots was the highest (4.19 fold higher than that of stems), followed by that of leaves (1.12 fold). Molecular characters of DoZIP1 will be useful for further functional determination of the gene involving in the growth and development of D. officinale.

Disruption of a cystine transporter downregulates expression of genes involved in sulfur regulation and cellular respiration

Directory of Open Access Journals (Sweden)

Jessica A. Simpkins

2016-06-01

Full Text Available Cystine and cysteine are important molecules for pathways such as redox signaling and regulation, and thus identifying cellular deficits upon deletion of the Saccharomyces cerevisiae cystine transporter Ers1p allows for a further understanding of cystine homeostasis. Previous complementation studies using the human ortholog suggest yeast Ers1p is a cystine transporter. Human CTNS encodes the protein Cystinosin, a cystine transporter that is embedded in the lysosomal membrane and facilitates the export of cystine from the lysosome. When CTNS is mutated, cystine transport is disrupted, leading to cystine accumulation, the diagnostic hallmark of the lysosomal storage disorder cystinosis. Here, we provide biochemical evidence for Ers1p-dependent cystine transport. However, the accumulation of intracellular cystine is not observed when the ERS1 gene is deleted from ers1-Δ yeast, supporting the existence of modifier genes that provide a mechanism in ers1-Δ yeast that prevents or corrects cystine accumulation. Upon comparison of the transcriptomes of isogenic ERS1+ and ers1-Δ strains of S. cerevisiae by DNA microarray followed by targeted qPCR, sixteen genes were identified as being differentially expressed between the two genotypes. Genes that encode proteins functioning in sulfur regulation, cellular respiration, and general transport were enriched in our screen, demonstrating pleiotropic effects of ers1-Δ. These results give insight into yeast cystine regulation and the multiple, seemingly distal, pathways that involve proper cystine recycling.

Regulation of dopamine transporter activity by carboxypeptidase E

Directory of Open Access Journals (Sweden)

Zhang Heping

2009-05-01

Full Text Available Abstract Background The dopamine transporter (DAT plays a critical role in terminating the action of dopamine by rapid reuptake into the presynaptic neuron. Previous studies have revealed that the DAT carboxyl terminus (DAT-CT can directly interact with other cellular proteins and regulate DAT function and trafficking. Results Here, we have identified that carboxypeptidase E (CPE, a prohormone processing exopeptidase and sorting receptor for the regulated secretory pathway, interacts with the DAT-CT and affects DAT function. Mammalian cell lines coexpressing CPE and DAT exhibited increased DAT-mediated dopamine uptake activity compared to cells expressing DAT alone. Moreover, coexpression of an interfering DAT-CT minigene inhibited the effects of CPE on DAT. Functional changes caused by CPE could be attributed to enhanced DAT expression and subsequent increase in DAT cell surface localization, due to decreased DAT degradation. In addition, CPE association could reduce the phosphorylation state of DAT on serine residues, potentially leading to reduced internalization, thus stabilizing plasmalemmal DAT localization. Conclusion Taken together, our results reveal a novel role for CPE in the regulation of DAT trafficking and DAT-mediated DA uptake, which may provide a novel target in the treatment of dopamine-governed diseases such as drug addiction and obesity.

Implementation of the 1996 edition of the IAEA regulations for the safe transport of radioactive material

International Nuclear Information System (INIS)

Rawl, R.R.; Kervella, O.

1998-01-01

The International Atomic Energy Agency (IAEA) completed a 10 year and revision of its 'Regulations for the Safe Transport of Radioactive Material' with approval of the amendments by its Board of Governors in September 1996. The revised edition contains some important changes in the regulations, including: type C package requirements; provisions for low dispersible material; uranium hexafluoride packaging; exemption value specifications; operational requirements, including the creation of a criticality safety index and new proper shipping names/UN numbers. The 1996 edition of the IAEA regulations has been published and corresponding revisions now being considered by the international transport safety organizations and Member States. In particular, the United Nations Committee of Experts on the Transport of Dangerous Goods, International Civil Aviation Organization and International Maritime Organization and preparing revisions to take into account the revised Class 7 requirements. An effective date of 1 January 2001 has been recommended so that international and domestic requirements might come into force simultaneously, thereby avoiding disruptive out-of-phase implementation. (authors)

The Myriad Roles of Miro in the Nervous System: Axonal Transport of Mitochondria and Beyond

Directory of Open Access Journals (Sweden)

Bingwei eLu

2014-10-01

Full Text Available Mitochondrial rho GTPase (Miro is a mitochondrial outer membrane protein containing two GTPase domains and two helix-loop-helix Ca2+-binding domains called EF hands. Pioneering genetic studies in Drosophila first revealed a key function of Miro in regulating the axonal transport of mitochondria, during which Miro forms a multi-protein transport complex with Milton and Kinesin heavy chain (KHC to link trafficking mitochondria with the microtubule cytoskeleton. Recent studies showed that through binding to the EF hands of Miro and causing conformational changes of Miro and alteration of protein-protein interactions within the transport complex, Ca2+ can alter the engagement of mitochondria with the microtubule (MT/kinesin network, offering one mechanism to match mitochondrial distribution with neuronal activity. Despite the importance of the Miro/Milton/Kinesin complex in regulating mitochondrial transport in metazoans, not all components of the transport complex are conserved in lower organisms, and transport-independent functions of Miro are emerging. Here we review the diverse functions of the evolutionarily conserved Miro proteins that are relevant to the development, maintenance, and functioning of the nervous system and discuss the potential contribution of Miro dysfunction to the pathogenesis of diseases of the nervous system.

The regulation of glucose transport in the heart of control and diabetic rats: With special emphasis on the glucose transporter

International Nuclear Information System (INIS)

Pleta, M. de Leoz.

1989-01-01

Glucose transport regulation with insulin and high perfusion pressure in the perfused rat hearts from control and diabetic rat hearts was investigated. [ 3 H]-cytochalasin B binding assay was used to study the distribution of glucose transporters within the subcellular membranes fractionated by linear sucrose density gradient centrifugation. In the present study, insulin increased glucose uptake in the perfused heart of control and diabetic animals. This coincided with an increase of glucose transporters on the plasma membrane. The increase in glucose transporters on the plasma membrane could not be accounted for by a decrease of glucose transporters from the microsomal membranes. High perfusion pressure did not change the number of glucose transporters on the plasma membrane compared to basal in the control and diabetic animals, though it increased glucose uptake above that observed for insulin in the control. Instead, high perfusion pressure altered the distribution of glucose transporters within the subcellular membranes in reverse to that with insulin, increasing an intermediate membrane pool believed to reside between the plasma membrane and microsomal membranes as well as the intracellular membrane pool

THE CONFORMITY OF MACHINE TOOLS WITH RESPECT TO EUROPEAN SAFETY STANDARDS

CERN Multimedia

TIS/TE

2001-01-01

European regulations require that all motorized machine tools conform to the latest safety standards by the end of the year 2000. CERN must follow these regulations and has already modified most of its machine tools accordingly. However, there is still a small number of machine tools which have not yet been modified as required. These machines should not be used until they are brought up to the required safety standards, failing which the machines should be discarded. One can recognise which machine tools conform with the latest standards by the indication 'CS' on the identification plate of the machine, see foto below. In cases of doubt about the status of a machine tool you should contact K. Altherr/EST or C. Margaroli/TIS for advice.

THE CONFORMITY OF MACHINE TOOLS WITH RESPECT TO EUROPEAN SAFETY STANDARDS

CERN Multimedia

TIS/TE

2000-01-01

European regulations require that all motorized machine tools conform to the latest safety standards by the end of the year 2000. CERN must follow these regulations and has already modified most of its machine tools accordingly. However, there is still a small number of machine tools which have not yet been modified as required. These machines should not be used until they are brought up to the required safety standards, failing which the machines should be discarded. One can recognise which machine tools conform with the latest standards by the indication 'CS' on the identification plate of the machine, see foto below. In cases of doubt about the status of a machine tool you should contact K. Altherr/EST or C. Margaroli/TIS for advice.

GABA signalling modulates plant growth by directly regulating the activity of plant-specific anion transporters.

Science.gov (United States)

Ramesh, Sunita A; Tyerman, Stephen D; Xu, Bo; Bose, Jayakumar; Kaur, Satwinder; Conn, Vanessa; Domingos, Patricia; Ullah, Sana; Wege, Stefanie; Shabala, Sergey; Feijó, José A; Ryan, Peter R; Gilliham, Matthew; Gillham, Matthew

2015-07-29

The non-protein amino acid, gamma-aminobutyric acid (GABA) rapidly accumulates in plant tissues in response to biotic and abiotic stress, and regulates plant growth. Until now it was not known whether GABA exerts its effects in plants through the regulation of carbon metabolism or via an unidentified signalling pathway. Here, we demonstrate that anion flux through plant aluminium-activated malate transporter (ALMT) proteins is activated by anions and negatively regulated by GABA. Site-directed mutagenesis of selected amino acids within ALMT proteins abolishes GABA efficacy but does not alter other transport properties. GABA modulation of ALMT activity results in altered root growth and altered root tolerance to alkaline pH, acid pH and aluminium ions. We propose that GABA exerts its multiple physiological effects in plants via ALMT, including the regulation of pollen tube and root growth, and that GABA can finally be considered a legitimate signalling molecule in both the plant and animal kingdoms.

Protein Conformational Plasticity: the 'off-on' Switching Movement in Cdk5

International Nuclear Information System (INIS)

Cavalli, Andrea; Recanatini, Maurizio; Berteotti, Anna; Branduardi, Davide; Gervasio, Francesco L.; Parrinello, Michele

2007-01-01

Cyclin-dependent kinases (CDKs) are mostly known for their role in the cell cycle regulation. The activation mechanism of all CDKs involves the association with a regulatory protein, generally a cyclin, that binds to the kinase unit and stabilizes a catalytically active conformation. Active and inactive conformations of CDKs are characterized by the different spatial localization of two typical elements, namely the activation loop and an □-helix, whose amino-acid composition varies throughout the family

Changes in the regulations for the safe transport of radioactive material

International Nuclear Information System (INIS)

Lopez Vietri, Jorge R.; Vidal, Dora N.; Piumetti, Elsa H.; Capadona, Nancy M.

2000-01-01

The objective of this paper is to describe and to analyze the relevant changes, dealing with the design, operation and administrative requirements, to be introduced in the Revision 1 of the AR 10.16.1 standard 'Transport of radioactive material' that will be put into force on July, 1st 2001 by the Nuclear Regulatory Authority (competent authority of Argentina). In that way, the Revision 1 of the mentioned standard will be coincident with the 1996 edition (revised) of the 'Regulations for the safe transport of radioactive material', Safety Standards Series No. TS-R-1 (ST-1, revised) issued by the International Atomic Energy Agency (IAEA). (author)

Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes

Science.gov (United States)

Fuente-Martín, Esther; García-Cáceres, Cristina; Granado, Miriam; de Ceballos, María L.; Sánchez-Garrido, Miguel Ángel; Sarman, Beatrix; Liu, Zhong-Wu; Dietrich, Marcelo O.; Tena-Sempere, Manuel; Argente-Arizón, Pilar; Díaz, Francisca; Argente, Jesús; Horvath, Tamas L.; Chowen, Julie A.

2012-01-01

Glial cells perform critical functions that alter the metabolism and activity of neurons, and there is increasing interest in their role in appetite and energy balance. Leptin, a key regulator of appetite and metabolism, has previously been reported to influence glial structural proteins and morphology. Here, we demonstrate that metabolic status and leptin also modify astrocyte-specific glutamate and glucose transporters, indicating that metabolic signals influence synaptic efficacy and glucose uptake and, ultimately, neuronal function. We found that basal and glucose-stimulated electrical activity of hypothalamic proopiomelanocortin (POMC) neurons in mice were altered in the offspring of mothers fed a high-fat diet. In adulthood, increased body weight and fasting also altered the expression of glucose and glutamate transporters. These results demonstrate that whole-organism metabolism alters hypothalamic glial cell activity and suggest that these cells play an important role in the pathology of obesity. PMID:23064363

Membrane transport mechanism 3D structure and beyond

CERN Document Server

Ziegler, Christine

2014-01-01

This book provides a molecular view of membrane transport by means of numerous biochemical and biophysical techniques. The rapidly growing number of atomic structures of transporters in different conformations and the constant progress in bioinformatics have recently added deeper insights.   The unifying mechanism of energized solute transport across membranes is assumed to consist of the conformational cycling of a carrier protein to provide access to substrate binding sites from either side of a cellular membrane. Due to the central role of active membrane transport there is considerable interest in deciphering the principles of one of the most fundamental processes in nature: the alternating access mechanism.   This book brings together particularly significant structure-function studies on a variety of carrier systems from different transporter families: Glutamate symporters, LeuT-like fold transporters, MFS transporters and SMR (RND) exporters, as well as ABC-type importers.   The selected examples im...

The metal chaperone Atox1 regulates the activity of the human copper transporter ATP7B by modulating domain dynamics.

Science.gov (United States)

Yu, Corey H; Yang, Nan; Bothe, Jameson; Tonelli, Marco; Nokhrin, Sergiy; Dolgova, Natalia V; Braiterman, Lelita; Lutsenko, Svetlana; Dmitriev, Oleg Y

2017-11-03

The human transporter ATP7B delivers copper to the biosynthetic pathways and maintains copper homeostasis in the liver. Mutations in ATP7B cause the potentially fatal hepatoneurological disorder Wilson disease. The activity and intracellular localization of ATP7B are regulated by copper, but the molecular mechanism of this regulation is largely unknown. We show that the copper chaperone Atox1, which delivers copper to ATP7B, and the group of the first three metal-binding domains (MBD1-3) are central to the activity regulation of ATP7B. Atox1-Cu binding to ATP7B changes domain dynamics and interactions within the MBD1-3 group and activates ATP hydrolysis. To understand the mechanism linking Atox1-MBD interactions and enzyme activity, we have determined the MBD1-3 conformational space using small angle X-ray scattering and identified changes in MBD dynamics caused by apo -Atox1 and Atox1-Cu by solution NMR. The results show that copper transfer from Atox1 decreases domain interactions within the MBD1-3 group and increases the mobility of the individual domains. The N-terminal segment of MBD1-3 was found to interact with the nucleotide-binding domain of ATP7B, thus physically coupling the domains involved in copper binding and those involved in ATP hydrolysis. Taken together, the data suggest a regulatory mechanism in which Atox1-mediated copper transfer activates ATP7B by releasing inhibitory constraints through increased freedom of MBD1-3 motions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Conformity and dietary disinhibition: a test of the ego-strength model of self-regulation.

Science.gov (United States)

Kahan, Dana; Polivy, Janet; Herman, C Peter

2003-03-01

Ego-strength depletion was examined as an explanation for dietary disinhibition in restrained eaters. We predicted that the depletion of ego strength resulting from having to choose whether to conform would undermine dietary restraint. Participants completed an Asch-type conformity task, after which they completed a taste-rating task in which food intake was measured. As predicted, restrained eaters who repeatedly exercised choice ate significantly more than did restrained eaters who did not exercise choice. An ego-strength model of dietary restraint is discussed. Copyright 2003 by Wiley Periodicals, Inc.

The transcriptional regulator, CosR, controls compatible solute biosynthesis and transport, motility and biofilm formation in Vibrio cholerae.

Science.gov (United States)

Shikuma, Nicholas J; Davis, Kimberly R; Fong, Jiunn N C; Yildiz, Fitnat H

2013-05-01

Vibrio cholerae inhabits aquatic environments and colonizes the human digestive tract to cause the disease cholera. In these environments, V. cholerae copes with fluctuations in salinity and osmolarity by producing and transporting small, organic, highly soluble molecules called compatible solutes, which counteract extracellular osmotic pressure. Currently, it is unclear how V. cholerae regulates the expression of genes important for the biosynthesis or transport of compatible solutes in response to changing salinity or osmolarity conditions. Through a genome-wide transcriptional analysis of the salinity response of V. cholerae, we identified a transcriptional regulator we name CosR for compatible solute regulator. The expression of cosR is regulated by ionic strength and not osmolarity. A transcriptome analysis of a ΔcosR mutant revealed that CosR represses genes involved in ectoine biosynthesis and compatible solute transport in a salinity-dependent manner. When grown in salinities similar to estuarine environments, CosR activates biofilm formation and represses motility independently of its function as an ectoine regulator. This is the first study to characterize a compatible solute regulator in V. cholerae and couples the regulation of osmotic tolerance with biofilm formation and motility. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

Study on TenneT profits 2010. Regulated Transport and System Tasks; Onderzoek winsten TenneT 2010. Gereguleerde Transport- en Systeemtaken

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-04-15

Research has been done on the profits realized by TenneT in 2010 with its regulated distribution and system tasks. The regulation method enables TenneT to recover its costs and realize a reasonable profit [Dutch] Onderzoek is gedaan naar het rendement dat TenneT in 2010 heeft behaald met de uitvoering van zijn gereguleerde transport- en systeemtaken. TenneT is door de reguleringsmethodiek in staat zijn efficiente kosten terug te verdienen en een redelijk rendement te behalen.

Molecular Dynamics Simulations of the Human Glucose Transporter GLUT1.

Directory of Open Access Journals (Sweden)

Min-Sun Park

Full Text Available Glucose transporters (GLUTs provide a pathway for glucose transport across membranes. Human GLUTs are implicated in devastating diseases such as heart disease, hyper- and hypo-glycemia, type 2 diabetes and cancer. The human GLUT1 has been recently crystalized in the inward-facing open conformation. However, there is no other structural information for other conformations. The X-ray structures of E. coli Xylose permease (XylE, a glucose transporter homolog, are available in multiple conformations with and without the substrates D-xylose and D-glucose. XylE has high sequence homology to human GLUT1 and key residues in the sugar-binding pocket are conserved. Here we construct a homology model for human GLUT1 based on the available XylE crystal structure in the partially occluded outward-facing conformation. A long unbiased all atom molecular dynamics simulation starting from the model can capture a new fully opened outward-facing conformation. Our investigation of molecular interactions at the interface between the transmembrane (TM domains and the intracellular helices (ICH domain in the outward- and inward-facing conformation supports that the ICH domain likely stabilizes the outward-facing conformation in GLUT1. Furthermore, inducing a conformational transition, our simulations manifest a global asymmetric rocker switch motion and detailed molecular interactions between the substrate and residues through the water-filled selective pore along a pathway from the extracellular to the intracellular side. The results presented here are consistent with previously published biochemical, mutagenesis and functional studies. Together, this study shed light on the structure and functional relationships of GLUT1 in multiple conformational states.

Unifying Concept of Serotonin Transporter-associated Currents*

Science.gov (United States)

Schicker, Klaus; Uzelac, Zeljko; Gesmonde, Joan; Bulling, Simon; Stockner, Thomas; Freissmuth, Michael; Boehm, Stefan; Rudnick, Gary; Sitte, Harald H.; Sandtner, Walter

2012-01-01

Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents. PMID:22072712

Unifying concept of serotonin transporter-associated currents.

Science.gov (United States)

Schicker, Klaus; Uzelac, Zeljko; Gesmonde, Joan; Bulling, Simon; Stockner, Thomas; Freissmuth, Michael; Boehm, Stefan; Rudnick, Gary; Sitte, Harald H; Sandtner, Walter

2012-01-02

Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents.

A thermodynamic and theoretical view for enzyme regulation.

Science.gov (United States)

Zhao, Qinyi

2015-01-01

Precise regulation is fundamental to the proper functioning of enzymes in a cell. Current opinions about this, such as allosteric regulation and dynamic contribution to enzyme regulation, are experimental models and substantially empirical. Here we proposed a theoretical and thermodynamic model of enzyme regulation. The main idea is that enzyme regulation is processed via the regulation of abundance of active conformation in the reaction buffer. The theoretical foundation, experimental evidence, and experimental criteria to test our model are discussed and reviewed. We conclude that basic principles of enzyme regulation are laws of protein thermodynamics and it can be analyzed using the concept of distribution curve of active conformations of enzymes.

Price cap regulation: the case of natural gas transport in the UK; La reglementation par price cap: le cas du transport de gaz naturel au Royaume Uni

Energy Technology Data Exchange (ETDEWEB)

David, L. [ATER, Paris-1 Univ., 75 (France)

1999-09-01

The transport and storage activities of British Gas company are controlled by a distinct organization named Transco. The access charges paid by the suppliers for the use of Transco's network are regulated by a price cap since October 1, 1994. However, Ofgas, the office of gas supply which is the regulation authority in charge of the control of competition and of British Gas activities, considers this control system as inefficient and has chosen a RPI (retail price index)-X (expected productivity factor)-type price cap for the control of gas transport tariffs. This has led to a disagreement between Transco and Ofgas which has delayed the implementation of the new system up to February 1998. This article compares the choices made by Ofgas for the control of gas transport tariffs with the economical theory. It recalls first, the reasons why the price cap appears as more efficient than the service cost regulation, the alternate method used by regulation authorities to control the tariffs of natural monopolies. Then, the difficulties linked with the implementation of the price cap for the transport of natural gas in the UK are analyzed in order to explain the reasons that led Ofgas to change its formula. Finally, the bases of an optimum hybrid formula are proposed. (J.S.)

In Silico Analysis of the Regulation of the Photosynthetic Electron Transport Chain in C3 Plants1[OPEN

Science.gov (United States)

Kramer, David M.

2018-01-01

We present a new simulation model of the reactions in the photosynthetic electron transport chain of C3 species. We show that including recent insights about the regulation of the thylakoid proton motive force, ATP/NADPH balancing mechanisms (cyclic and noncyclic alternative electron transport), and regulation of Rubisco activity leads to emergent behaviors that may affect the operation and regulation of photosynthesis under different dynamic environmental conditions. The model was parameterized with experimental results in the literature, with a focus on Arabidopsis (Arabidopsis thaliana). A dataset was constructed from multiple sources, including measurements of steady-state and dynamic gas exchange, chlorophyll fluorescence, and absorbance spectroscopy under different light intensities and CO2, to test predictions of the model under different experimental conditions. Simulations suggested that there are strong interactions between cyclic and noncyclic alternative electron transport and that an excess capacity for alternative electron transport is required to ensure adequate redox state and lumen pH. Furthermore, the model predicted that, under specific conditions, reduction of ferredoxin by plastoquinol is possible after a rapid increase in light intensity. Further analysis also revealed that the relationship between ATP synthesis and proton motive force was highly regulated by the concentrations of ATP, ADP, and inorganic phosphate, and this facilitated an increase in nonphotochemical quenching and proton motive force under conditions where metabolism was limiting, such as low CO2, high light intensity, or combined high CO2 and high light intensity. The model may be used as an in silico platform for future research on the regulation of photosynthetic electron transport. PMID:28924017

Quantum Conformal Algebras and Closed Conformal Field Theory

CERN Document Server

Anselmi, D

1999-01-01

We investigate the quantum conformal algebras of N=2 and N=1 supersymmetric gauge theories. Phenomena occurring at strong coupling are analysed using the Nachtmann theorem and very general, model-independent, arguments. The results lead us to introduce a novel class of conformal field theories, identified by a closed quantum conformal algebra. We conjecture that they are the exact solution to the strongly coupled large-N_c limit of the open conformal field theories. We study the basic properties of closed conformal field theory and work out the operator product expansion of the conserved current multiplet T. The OPE structure is uniquely determined by two central charges, c and a. The multiplet T does not contain just the stress-tensor, but also R-currents and finite mass operators. For this reason, the ratio c/a is different from 1. On the other hand, an open algebra contains an infinite tower of non-conserved currents, organized in pairs and singlets with respect to renormalization mixing. T mixes with a se...

C-metric solution for conformal gravity with a conformally coupled scalar field

Energy Technology Data Exchange (ETDEWEB)

Meng, Kun, E-mail: mengkun@tjpu.edu.cn [School of Science, Tianjin Polytechnic University, Tianjin 300387 (China); Zhao, Liu, E-mail: lzhao@nankai.edu.cn [School of Physics, Nankai University, Tianjin 300071 (China)

2017-02-15

The C-metric solution of conformal gravity with a conformally coupled scalar field is presented. The solution belongs to the class of Petrov type D spacetimes and is conformal to the standard AdS C-metric appeared in vacuum Einstein gravity. For all parameter ranges, we identify some of the physically interesting static regions and the corresponding coordinate ranges. The solution may contain a black hole event horizon, an acceleration horizon, either of which may be cut by the conformal infinity or be hidden behind the conformal infinity. Since the model is conformally invariant, we also discussed the possible effects of the conformal gauge choices on the structure of the spacetime.

Transport systems of Ventricaria ventricosa: asymmetry of the hyper- and hypotonic regulation mechanisms.

Science.gov (United States)

Bisson, M A; Beilby, M J

2008-01-01

Hyper- and hypotonic stresses elicit apparently symmetrical responses in the alga Ventricaria. With hypertonic stress, membrane potential difference (PD) between the vacuole and the external medium becomes more positive, conductance at positive PDs (Gmpos) increases and KCl is actively taken up to increase turgor. With hypotonic stress, the membrane PD becomes more negative, conductance at negative PDs (Gmneg) increases and KCl is lost to decrease turgor. We used inhibitors that affect active transport to determine whether agents that inhibit the K(+) pump and hypertonic regulation also inhibit hypotonic regulatory responses. Cells whose turgor pressure was held low by the pressure probe (turgor-clamped) exhibited the same response as cells challenged by hyperosmotic medium, although the response was maintained longer than in osmotically challenged cells, which regulate turgor. The role of active K(+) transport was confirmed by the effects of decreased light, dichlorophenyldimethyl urea and diethylstilbestrol, which induced a uniformly low conductance (quiet state). Cells clamped to high turgor exhibited the same response as cells challenged by hypo-osmotic medium, but the response was similarly transient, making effects of inhibitors hard to determine. Unlike clamped cells, cells challenged by hypo-osmotic medium responded to inhibitors with rapid, transient, negative-going PDs, with decreased Gmneg and increased Gmpos (linearized I-V), achieving the quiet state as PD recovered. These changes are different from those exerted on the pump state, indicating that different transport systems are responsible for turgor regulation in the two cases.

Cholesterol-induced conformational changes in the sterol-sensing domain of the Scap protein suggest feedback mechanism to control cholesterol synthesis.

Science.gov (United States)

Gao, Yansong; Zhou, Yulian; Goldstein, Joseph L; Brown, Michael S; Radhakrishnan, Arun

2017-05-26

Scap is a polytopic protein of endoplasmic reticulum (ER) membranes that transports sterol regulatory element-binding proteins to the Golgi complex for proteolytic activation. Cholesterol accumulation in ER membranes prevents Scap transport and decreases cholesterol synthesis. Previously, we provided evidence that cholesterol inhibition is initiated when cholesterol binds to loop 1 of Scap, which projects into the ER lumen. Within cells, this binding causes loop 1 to dissociate from loop 7, another luminal Scap loop. However, we have been unable to demonstrate this dissociation when we added cholesterol to isolated complexes of loops 1 and 7. We therefore speculated that the dissociation requires a conformational change in the intervening polytopic sequence separating loops 1 and 7. Here we demonstrate such a change using a protease protection assay in sealed membrane vesicles. In the absence of cholesterol, trypsin or proteinase K cleaved cytosolic loop 4, generating a protected fragment that we visualized with a monoclonal antibody against loop 1. When cholesterol was added to these membranes, cleavage in loop 4 was abolished. Because loop 4 is part of the so-called sterol-sensing domain separating loops 1 and 7, these results support the hypothesis that cholesterol binding to loop 1 alters the conformation of the sterol-sensing domain. They also suggest that this conformational change helps transmit the cholesterol signal from loop 1 to loop 7, thereby allowing separation of the loops and facilitating the feedback inhibition of cholesterol synthesis. These insights suggest a new structural model for cholesterol-mediated regulation of Scap activity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The ESCRT regulator Did2 maintains the balance between long-distance endosomal transport and endocytic trafficking.

Directory of Open Access Journals (Sweden)

Carl Haag

2017-04-01

Full Text Available In highly polarised cells, like fungal hyphae, early endosomes function in both endocytosis as well as long-distance transport of various cargo including mRNA and protein complexes. However, knowledge on the crosstalk between these seemingly different trafficking processes is scarce. Here, we demonstrate that the ESCRT regulator Did2 coordinates endosomal transport in fungal hyphae of Ustilago maydis. Loss of Did2 results in defective vacuolar targeting, less processive long-distance transport and abnormal shuttling of early endosomes. Importantly, the late endosomal protein Rab7 and vacuolar protease Prc1 exhibit increased shuttling on these aberrant endosomes suggesting defects in endosomal maturation and identity. Consistently, molecular motors fail to attach efficiently explaining the disturbed processive movement. Furthermore, the endosomal mRNP linker protein Upa1 is hardly present on endosomes resulting in defects in long-distance mRNA transport. In conclusion, the ESCRT regulator Did2 coordinates precise maturation of endosomes and thus provides the correct membrane identity for efficient endosomal long-distance transport.

In silico analysis of the regulation of the photosynthetic electron transport chain in C3 plants

NARCIS (Netherlands)

Morales Sierra, A.; Yin, Xinyou; Harbinson, Jeremy; Driever, Steven Michiel; Molenaar, Jaap; Kramer, David M.; Struik, Paul

2018-01-01

We present a new simulation model of the reactions in the photosynthetic electron transport chain of C3 species. We show that including recent insights about the regulation of the thylakoid proton motive force, ATP/NADPH balancing mechanisms (cyclic and non-cyclic alternative electron transport),

S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

Science.gov (United States)

Fang, Chao; Bian, Ganlan; Ren, Pan; Xiang, Jie; Song, Jun; Yu, Caiyong; Zhang, Qian; Liu, Ling; Chen, Kun; Liu, Fangfang; Zhang, Kun; Wu, Chunfeng; Sun, Ruixia; Hu, Dan; Ju, Gong; Wang, Jian

2018-02-08

Spinster homolog 2 (SPNS2) is the membrane transporter of sphingosine-1-phosphate (S1P), and it participates in several physiologic processes by activating different S1P receptors (S1PRs). However, its functions in the nervous system remain largely unclear. We explored the important role of SPNS2 in the process of retinal morphogenesis using a spns2-deficient rat model. In the absence of the functional SPNS2 transporter, we observed progressively aggravating laminar disorganization of the epithelium at the postnatal stage of retinal development. Disrupted cell polarity, delayed cell-cycle exit of retinal progenitor cells, and insufficient migration of newborn neurons were proposed in this study as potential mechanisms accounting for this structural disorder. In addition, we analyzed the expression profiles of spns2 and s1prs, and proposed that SPNS2 regulated retinal morphogenesis by establishing the S1P level in the eye and activating S1PR3 signaling. These data indicate that SPNS2 is indispensable for normal retinal morphogenesis and provide new insights on the role of S1P in the developing retina using an established in vivo model.-Fang, C., Bian, G., Ren, P., Xiang, J., Song, J., Yu, C., Zhang, Q., Liu, L., Chen, K., Liu, F., Zhang, K., Wu, C., Sun, R., Hu, D., Ju, G., Wang, J. S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

Systemic and local regulation of phosphate and nitrogen transporter genes by arbuscular mycorrhizal fungi in roots of winter wheat (Triticum aestivum L.).

Science.gov (United States)

Duan, Jianfeng; Tian, Hui; Drijber, Rhae A; Gao, Yajun

2015-11-01

Previous studies have reported that the expression of phosphate (Pi) or nitrogen (N) transporter genes in roots of plants could be regulated by arbuscular mycorrhizal (AM) fungi, but little is known whether the regulation is systemic or not. The present study investigated the systemic and local regulation of multiple phosphate and nitrogen transporter genes by four AM fungal species belonging to four genera in the roots of winter wheat. A split-root culture system with AM inoculated (MR) and non-inoculated root compartments (NR) was used to investigate the systemic or local responses of phosphate and nitrogen transporter genes to colonization by four AM fungi in the roots of wheat. The expression of four Pi transporter, five nitrate transporter, and three ammonium transporter genes was quantified using real-time PCR. Of the four AM fungi tested, all locally increased expression of the AM-inducible Pi transporter genes, and most locally decreased expression of a Pi-starvation inducible Pi transporter gene. The addition of N in soil increased the expression of either Pi starvation inducible Pi transporters or AM inducible Pi transporters. Inoculation with AM fungi either had no effect, or could locally or systemically down-regulate expression of nitrogen transporter genes depending on gene type and AM fungal species. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Serotonin transporter evolution and impact of polymorphic transcriptional regulation

DEFF Research Database (Denmark)

Søeby, Karen; Larsen, Svend Ask; Olsen, Line

2005-01-01

The serotonin transporter (SERT) is the primary drug target in the current antidepressant therapy. A functional polymorphism in the 2nd intron of the 5HTT gene encoding the SERT has been identified and associated with susceptibility to affective disorders and treatment response to antidepressants....... This study addresses the possible impact of the variable number of tandem repeats (VNTR) to behavior and disease by examining the evolutionary origin and mechanisms of differential transcriptional regulation of SERT. We trace the evolutionary origin of the VNTR and show that it is present and varies...

Serotonin transporter evolution and impact of polymorphic transcriptional regulation

DEFF Research Database (Denmark)

Søeby, Karen; Larsen, Svend Ask; Olsen, Line

2005-01-01

The serotonin transporter (SERT) is the primary drug target in the current antidepressant therapy. A functional polymorphism in the 2nd intron of the 5HTT gene encoding the SERT has been identified and associated with susceptibility to affective disorders and treatment response to antidepressants...... in the VNTRs of all mammalian SERT genes. The number of these putative binding sites varies proportionally to the length of the VNTR. We propose that the intronic VNTR have been selectively targeted through mammalian evolution to finetune transcriptional regulation of the serotonin expression....

Repeat-swap homology modeling of secondary active transporters: updated protocol and prediction of elevator-type mechanisms.

Science.gov (United States)

Vergara-Jaque, Ariela; Fenollar-Ferrer, Cristina; Kaufmann, Desirée; Forrest, Lucy R

2015-01-01

Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to one or other side of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (a)symmetry of these systems has been successfully used as a bioinformatic tool, called "repeat-swap modeling" to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that nucleoside transport also

Repeat-swap homology modeling of secondary active transporters: updated protocol and prediction of elevator-type mechanisms

Directory of Open Access Journals (Sweden)

Cristina eFenollar Ferrer

2015-09-01

Full Text Available Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to either the outside or inside of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (asymmetry of these systems has been successfully used as a bioinformatic tool, called repeat-swap modeling to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that

Non-conformable, partial and conformable transposition

DEFF Research Database (Denmark)

König, Thomas; Mäder, Lars Kai

2013-01-01

and the Commission regarding a directive’s outcome, play a much more strategic role than has to date acknowledged in the transposition literature. Whereas disagreement of a member state delays conformable transposition, it speeds up non-conformable transposition. Disagreement of the Commission only prolongs...... the transposition process. We therefore conclude that a stronger focus on an effective sanctioning mechanism is warranted for safeguarding compliance with directives....

Conformal Einstein spaces

International Nuclear Information System (INIS)

Kozameh, C.N.; Newman, E.T.; Tod, K.P.

1985-01-01

Conformal transformations in four-dimensional. In particular, a new set of two necessary and sufficient conditions for a space to be conformal to an Einstein space is presented. The first condition defines the class of spaces conformal to C spaces, whereas the last one (the vanishing of the Bach tensor) gives the particular subclass of C spaces which are conformally related to Einstein spaces. (author)

Conformal Gravity

International Nuclear Information System (INIS)

Hooft, G.

2012-01-01

The dynamical degree of freedom for the gravitational force is the metric tensor, having 10 locally independent degrees of freedom (of which 4 can be used to fix the coordinate choice). In conformal gravity, we split this field into an overall scalar factor and a nine-component remainder. All unrenormalizable infinities are in this remainder, while the scalar component can be handled like any other scalar field such as the Higgs field. In this formalism, conformal symmetry is spontaneously broken. An imperative demand on any healthy quantum gravity theory is that black holes should be described as quantum systems with micro-states as dictated by the Hawking-Bekenstein theory. This requires conformal symmetry that may be broken spontaneously but not explicitly, and this means that all conformal anomalies must cancel out. Cancellation of conformal anomalies yields constraints on the matter sector as described by some universal field theory. Thus black hole physics may eventually be of help in the construction of unified field theories. (author)

Potential impacts of ICRP 60 and 61 on the transportation regulations

International Nuclear Information System (INIS)

Rawl, R.R.; Eckerman, K.F.; Wangler, M.E.; Punch, F.; Carriker, A.W.

1992-01-01

The International Commission on Radiation Protection (ICRP) has been providing recommendations for limitations on radiation exposure for decades. The ICRP recommendations address ionizing radiation and are concerned with protecting humans from its effects. These recommendations assist regulatory and advisory agencies in establishing and promulgating national regulations and practices in radiation Protection. Most countries have incorporated at least some aspect of the recommendations in their regulations since about 1956 when the first basic prowdon standard was Published in ICRP 2. Since that time ICRP has issued two major revisions to the recommendations. ICRP 26 was published in 1977 and ICRP 60 was published in 1991. These last two publications have companion works, ICRP 30 atid ICRP 61, that contain Annual Limits of Intake (ALI) for radiation workers. This report discusses the impacts of ICRP 60 and 61 on transport regulations

Regulation of ABCB1/PGP1-catalysed auxin transport by linker phosphorylation

DEFF Research Database (Denmark)

Henrichs, Sina; Wang, Bangjun; Fukao, Yoichiro

2012-01-01

Polar transport of the plant hormone auxin is controlled by PIN-and ABCB/PGP-efflux catalysts. PIN polarity is regulated by the AGC protein kinase, PINOID (PID), while ABCB activity was shown to be dependent on interaction with the FKBP42, TWISTED DWARF1 (TWD1). Using co-immunoprecipitation (co-I...

Is contraction-stimulated glucose transport feedforward regulated by Ca²⁺?

DEFF Research Database (Denmark)

Jensen, Thomas Elbenhardt; Angin, Yeliz; Sylow, Lykke

2014-01-01

cell types. The literature is contrasted against our recent findings suggesting that SR Ca(2+) release is neither essential nor adequate to stimulate glucose transport in muscle. Instead, feedback signals through AMPK and mechanical stress are likely to account for most of contraction......In many cell types, Ca(2+) signals to increase the movement and surface membrane insertion of vesicles. In skeletal muscle, Ca(2+) is predominantly released from the sarcoplasmic reticulum (SR) to initiate contraction. Sarcoplasmic reticulum Ca(2+) release is widely believed to be a direct......-stimulated glucose transport. A revised working model is proposed, in which muscle glucose transport during contraction is not directly regulated by SR Ca(2+) release but rather responds exclusively to feedback signals activated secondary to cross-bridge cycling and tension development....

Multiple Drug Transport Pathways through Human P-Glycoprotein.

Science.gov (United States)

McCormick, James W; Vogel, Pia D; Wise, John G

2015-07-21

P-Glycoprotein (P-gp) is a plasma membrane efflux pump that is commonly associated with therapy resistances in cancers and infectious diseases. P-gp can lower the intracellular concentrations of many drugs to subtherapeutic levels by translocating them out of the cell. Because of the broad range of substrates transported by P-gp, overexpression of P-gp causes multidrug resistance. We reported previously on dynamic transitions of P-gp as it moved through conformations based on crystal structures of homologous ABCB1 proteins using in silico targeted molecular dynamics techniques. We expanded these studies here by docking transport substrates to drug binding sites of P-gp in conformations open to the cytoplasm, followed by cycling the pump through conformations that opened to the extracellular space. We observed reproducible transport of two substrates, daunorubicin and verapamil, by an average of 11-12 Å through the plane of the membrane as P-gp progressed through a catalytic cycle. Methylpyrophosphate, a ligand that should not be transported by P-gp, did not show this movement through P-gp. Drug binding to either of two subsites on P-gp appeared to determine the initial pathway used for drug movement through the membrane. The specific side-chain interactions with drugs within each pathway seemed to be, at least in part, stochastic. The docking and transport properties of a P-gp inhibitor, tariquidar, were also studied. A mechanism of inhibition by tariquidar that involves stabilization of an outward open conformation with tariquidar bound in intracellular loops or at the drug binding domain of P-gp is presented.

Relativistic conformal magneto-hydrodynamics from holography

International Nuclear Information System (INIS)

Buchbinder, Evgeny I.; Buchel, Alex

2009-01-01

We use the AdS/CFT correspondence to study first-order relativistic viscous magneto-hydrodynamics of (2+1)-dimensional conformal magnetic fluids. It is shown that the first order magneto-hydrodynamics constructed following Landau and Lifshitz from the positivity of the entropy production is inconsistent. We propose additional contributions to the entropy motivated dissipative current and, correspondingly, new dissipative transport coefficients. We use the strongly coupled M2-brane plasma in external magnetic field to show that the new magneto-hydrodynamics leads to self-consistent results in the shear and sound wave channels.

77 FR 48460 - Transportation of Household Goods in Interstate Commerce; Consumer Protection Regulations

Science.gov (United States)

2012-08-14

..., direct final rule concerning household goods consumer protection. The direct final rule amended the... No. FMCSA-2012-0119] RIN 2126-AB52 Transportation of Household Goods in Interstate Commerce; Consumer Protection Regulations AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Direct final...

Regulation of β2-adrenergic receptor function by conformationally selective single-domain intrabodies

DEFF Research Database (Denmark)

Staus, Dean P; Wingler, Laura M; Strachan, Ryan T

2014-01-01

. However, a monomeric single-domain antibody (nanobody) from the Camelid family was recently found to allosterically bind and stabilize an active conformation of the β2-adrenergic receptor (β2AR). Here, we set out to study the functional interaction of 18 related nanobodies with the β2AR to investigate...... their roles as novel tools for studying GPCR biology. Our studies revealed several sequence-related nanobody families with preferences for active (agonist-occupied) or inactive (antagonist-occupied) receptors. Flow cytometry analysis indicates that all nanobodies bind to epitopes displayed...... on the intracellular receptor surface; therefore, we transiently expressed them intracellularly as "intrabodies" to test their effects on β2AR-dependent signaling. Conformational specificity was preserved after intrabody conversion as demonstrated by the ability for the intracellularly expressed nanobodies...

Up-Regulation of Excitatory Amino Acid Transporters EAAT1 and EAAT2 by ß-Klotho

Directory of Open Access Journals (Sweden)

Jamshed Warsi

2015-12-01

Full Text Available Background/Aims: Klotho, a transmembrane protein expressed in chorioid plexus of the brain, kidney, and several other tissues, is required for inhibition of 1,25(OH2D3 formation by FGF23. The extracellular domain of Klotho protein could be cleaved off, thus being released into blood or cerebrospinal fluid. At least in part by exerting β-glucuronidase activity, soluble klotho regulates several ion channels and carriers. Klotho protein deficiency accelerates the appearance of age related disorders including neurodegeneration and muscle wasting and eventually leads to premature death. The present study explored the effect of Klotho protein on the excitatory glutamate transporters EAAT1 (SLC1A3 and EAAT2 (SLC1A2, Na+ coupled carriers clearing excitatory amino acids from the synaptic cleft and thus participating in the regulation of neuronal excitability. Methods: cRNA encoding EAAT1 or EAAT2 was injected into Xenopus laevis oocytes and glutamate (2 mM-induced inward current (IGlu taken as measure of glutamate transport. Measurements were made without or with prior 24 h treatment with soluble ß-Klotho protein (30 ng/ml in the absence and presence of β-glucuronidase inhibitor D-saccharic acid 1,4-lactone monohydrate (DSAL,10 µM. Results: IGlu was observed in EAAT1 and in EAAT2 expressing oocytes but not in water injected oocytes. In both, EAAT1 and EAAT2 expressing oocytes IGlu was significantly increased by treatment with soluble ß-Klotho protein, an effect reversed by DSAL. Treatment with ß-klotho protein increased significantly the maximal transport rate without significantly modifying the affinity of the carriers. Conclusion: ß-Klotho up-regulates the excitatory glutamate transporters EAAT1 and EAAT2 and thus participates in the regulation of neuronal excitation.

Sor/89-426, 24 August 1989, transport packaging of radioactive materials regulations, amendment

International Nuclear Information System (INIS)

1989-09-01

These Regulations of 24 September 1983 were amended mainly to clarify the original text and further specify certain requirements. In particular, the definitions of A 1 , A 2 , Fissile Class III package and special Form Radioactive Material have been revoked and replaced by new definitions. Also, a new condition has been added regarding Special Form Radioactive Material. Henceforth, no such material may be transported without a certificate attesting that the material meets the requirements set out in Schedule XII of the Regulations [fr

Regulatory authority of the Rocky Mountain states for low-level radioactive waste packaging and transportation

International Nuclear Information System (INIS)

Whitman, M.; Tate, P.

1983-07-01

The newly-formed Rocky Mountain Low-Level Radioactive Waste Compact is an interstate agreement for the management of low-level radioactive waste (LLW). Eligible members of the compact are Arizona, Colorado, Nevada, New Mexico, Utah, and Wyoming. Each state must ratify the compact within its legislature for the compact to become effective in that state and to make that state a full-fledged member of the compact. By so adopting the compact, each state agrees to the terms and conditions specified therein. Among those terms and conditions are provisions requiring each member state to adopt and enforce procedures requiring low-level waste shipments originating within its borders and destined for a regional facility to conform to packaging and transportation requirements and regulations. These procedures are to include periodic inspections of packaging and shipping practices, periodic inspections of waste containers while in the custody of carriers and appropriate enforcement actions for violations. To carry out this responsibility, each state must have an adequate statutory and regulatory inspection and enforcement authority to ensure the safe transportation of low-level radioactive waste. Three states in the compact region, Arizona, Utah and Wyoming, have incorporated the Department of Transportation regulations in their entirety, and have no published rules and regulations of their own. The other states in the compact, Colorado, Nevada and New Mexico all have separate rules and regulations that incorporate the DOT regulations. A brief description of the regulatory requirements of each state is presented

Prohibitin/annexin 2 interaction regulates fatty acid transport in adipose tissue

Science.gov (United States)

Salameh, Ahmad; Daquinag, Alexes C.; Staquicini, Daniela I.; An, Zhiqiang; Pasqualini, Renata; Kolonin, Mikhail G.

2016-01-01

We have previously identified prohibitin (PHB) and annexin A2 (ANX2) as proteins interacting on the surface of vascular endothelial cells in white adipose tissue (WAT) of humans and mice. Here, we demonstrate that ANX2 and PHB also interact in adipocytes. Mice lacking ANX2 have normal WAT vascularization, adipogenesis, and glucose metabolism but display WAT hypotrophy due to reduced fatty acid uptake by WAT endothelium and adipocytes. By using cell culture systems in which ANX2/PHB binding is disrupted either genetically or through treatment with a blocking peptide, we show that fatty acid transport efficiency relies on this protein complex. We also provide evidence that the interaction between ANX2 and PHB mediates fatty acid transport from the endothelium into adipocytes. Moreover, we demonstrate that ANX2 and PHB form a complex with the fatty acid transporter CD36. Finally, we show that the colocalization of PHB and CD36 on adipocyte surface is induced by extracellular fatty acids. Together, our results suggest that an unrecognized biochemical interaction between ANX2 and PHB regulates CD36-mediated fatty acid transport in WAT, thus revealing a new potential pathway for intervention in metabolic diseases. PMID:27468426

PPAR-α, a lipid-sensing transcription factor, regulates blood-brain barrier efflux transporter expression.

Science.gov (United States)

More, Vijay R; Campos, Christopher R; Evans, Rebecca A; Oliver, Keith D; Chan, Gary Ny; Miller, David S; Cannon, Ronald E

2017-04-01

Lipid sensor peroxisome proliferator-activated receptor alpha (PPAR- α) is the master regulator of lipid metabolism. Dietary release of endogenous free fatty acids, fibrates, and certain persistent environmental pollutants, e.g. perfluoroalkyl fire-fighting foam components, are peroxisome proliferator-activated receptor alpha ligands. Here, we define a role for peroxisome proliferator-activated receptor alpha in regulating the expression of three ATP-driven drug efflux transporters at the rat and mouse blood-brain barriers: P-glycoprotein (Abcb1), breast cancer resistance protein (Bcrp/Abcg2), and multidrug resistance-associated protein 2 (Mrp2/Abcc2). Exposing isolated rat brain capillaries to linoleic acid, clofibrate, or PKAs increased the transport activity and protein expression of the three ABC transporters. These effects were blocked by the PPAR- α antagonist, GW6471. Dosing rats with 20 mg/kg or 200 mg/kg of clofibrate decreased the brain accumulation of the P-glycoprotein substrate, verapamil, by 50% (in situ brain perfusion; effects blocked by GW6471) and increased P-glycoprotein expression and activity in capillaries ex vivo. Fasting C57Bl/6 wild-type mice for 24 h increased both serum lipids and brain capillary P-glycoprotein transport activity. Fasting did not alter P-glycoprotein activity in PPAR- α knockout mice. These results indicate that hyperlipidemia, lipid-lowering fibrates and exposure to certain fire-fighting foam components activate blood-brain barrier peroxisome proliferator-activated receptor alpha, increase drug efflux transporter expression and reduce drug delivery to the brain.

Identification of an Efflux Transporter LmrB Regulating Stress Response and Extracellular Polysaccharide Synthesis in Streptococcus mutans

Directory of Open Access Journals (Sweden)

Jia Liu

2017-06-01

Full Text Available Efflux transporters have been implicated in regulating bacterial virulence properties such as resistance to antibiotics, biofilm formation and colonization. The pathogenicity of Streptococcus mutans, the primary etiologic agent of human dental caries, relies on the bacterium’s ability to form biofilms on tooth surface. However, the studies on efflux transporters in S. mutans are scare and the function of these transporters remained to be clarified. In this study, we identified an efflux transporter (LmrB in S. mutans through cloning the lmrB gene into Escherichia coli. Introducing lmrB into E. coli conferred a multidrug-resistant phenotype and resulted in higher EtBr efflux activity which could be suppressed by efflux inhibitor. To explore whether LmrB was involved in S. mutans virulence properties regulation, we constructed the lmrB inactivation mutant and examined the phenotypes of the mutant. It was found that LmrB deficiency resulted in increased IPS storage and prolonged acid production. Enhanced biofilm formation characterized by increased extracellular polysaccharides (EPS production and elevated resistance to hydrogen peroxide and antimicrobials were also observed in lmrB mutant. To gain a better understanding of the global role of LmrB, a transcriptome analysis was performed using lmrB mutant strain. The expression of 107 genes was up- or down-regulated in the lmrB mutant compared with the wild type. Notably, expression of genes in several genomic islands was differentially modulated, such as stress-related GroELS and scnRK, sugar metabolism associated glg operons and msmREFGK transporter. The results presented here indicate that LmrB plays a vital global role in the regulation of several important virulence properties in S. mutans.

Conformal symmetry in two-dimensional space: recursion representation of conformal block

International Nuclear Information System (INIS)

Zamolodchikov, A.B.

1988-01-01

The four-point conformal block plays an important part in the analysis of the conformally invariant operator algebra in two-dimensional space. The behavior of the conformal block is calculated in the present paper in the limit in which the dimension Δ of the intermediate operator tends to infinity. This makes it possible to construct a recursion relation for this function that connects the conformal block at arbitrary Δ to the blocks corresponding to the dimensions of the zero vectors in the degenerate representations of the Virasoro algebra. The relation is convenient for calculating the expansion of the conformal block in powers of the uniformizing parameters q = i π tau

General Conformity Training Module 2.5: Proactive Role for Federal Agencies

Science.gov (United States)

Module 2.5 explains how taking a proactive role will allow a federal agency to more effectively participate in newly promulgated programs under the General Conformity Regulations, such as the emission reduction credits and the emission budgets programs.

Arrangements for transition from the 1985 edition (as amended 1990) to the 1996 edition of the IAEA Transport Regulations

International Nuclear Information System (INIS)

2001-03-01

The purpose of this publication is to provide guidance to National Competent Authorities to facilitate compliance during, and after, transition from the previous edition of the International Atomic Energy Agency's (IAEA's) Transport Regulations (Safety Series No. 6, 1985 Edition, as Amended 1990) to the 1996 editions (TS-R-1 [ST-1, Revised], in English; ST-1 in French, Russian and Spanish) of the regulations. This may also provide guidance to other users of the IAEA's Transport Regulations such as consignors, carriers, consignees, owners and designers and fabricators of radioactive material and package designers and fabrications

Specific character of sustainable innovative development of transport construction in self-regulation conditions

Science.gov (United States)

Gumba, Khuta; Belyaeva, Svetlana

2017-10-01

The providing of sustainable development is impossible without activating the innovative activity of backbone economical sectors, in particular of transport construction. The system of self-regulation of activities is a specific feature of the transport industry development. The authors carried out the correlation analysis of innovative activity of construction enterprises, which proved the necessity of improving the normative and technical documents. The authors proposed and calculated the index of the legislation stability in the industry. The article suggests recommendations on the activation of innovative development in construction industry basing on the results of the modeling.

National competent authorities. List no. 4. Regulations for the safe transport of radioactive materials. 1967 edition (Safety series no. 6)

International Nuclear Information System (INIS)

1971-06-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness

National competent authorities. List no. 17. Regulations for the safe transport of radioactive material. 1985 edition (Safety series no.6 )

Energy Technology Data Exchange (ETDEWEB)

NONE

1985-12-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness.

National competent authorities. List no. 5. Regulations for the safe transport of radioactive materials. 1967 edition (Safety series no. 6)

Energy Technology Data Exchange (ETDEWEB)

NONE

1972-09-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness.

National competent authorities. List no. 4. Regulations for the safe transport of radioactive materials. 1967 edition (Safety series no. 6)

Energy Technology Data Exchange (ETDEWEB)

NONE

1971-06-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness.

National competent authorities. List no. 1. Regulations for the safe transport of radioactive materials. 1967 edition (Safety series no. 6)

International Nuclear Information System (INIS)

1967-04-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness

National competent authorities. List no. 2. Regulations for the safe transport of radioactive materials. 1967 edition (Safety series no. 6)

International Nuclear Information System (INIS)

1968-08-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness

National competent authorities. List no. 3. Regulations for the safe transport of radioactive materials. 1967 edition (Safety series no. 6)

International Nuclear Information System (INIS)

1970-06-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness

National competent authorities. List no. 17. Regulations for the safe transport of radioactive material. 1985 edition (Safety series no.6 )

International Nuclear Information System (INIS)

1985-12-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness

National competent authorities. List no. 3. Regulations for the safe transport of radioactive materials. 1967 edition (Safety series no. 6)

Energy Technology Data Exchange (ETDEWEB)

NONE

1970-06-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness.

National competent authorities. List no. 2. Regulations for the safe transport of radioactive materials. 1967 edition (Safety series no. 6)

Energy Technology Data Exchange (ETDEWEB)

NONE

1968-08-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness.

National competent authorities. List no. 5. Regulations for the safe transport of radioactive materials. 1967 edition (Safety series no. 6)

International Nuclear Information System (INIS)

1972-09-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness

National competent authorities. List no. 1. Regulations for the safe transport of radioactive materials. 1967 edition (Safety series no. 6)

Energy Technology Data Exchange (ETDEWEB)

NONE

1967-04-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness.

On the physical origin of galactic conformity

Science.gov (United States)

Hearin, Andrew P.; Behroozi, Peter S.; van den Bosch, Frank C.

2016-09-01

Correlations between the star formation rates (SFRs) of nearby galaxies (so-called galactic conformity) have been observed for projected separations up to 4 Mpc, an effect not predicted by current semi-analytic models. We investigate correlations between the mass accretion rates (dMvir/dt) of nearby haloes as a potential physical origin for this effect. We find that pairs of host haloes `know about' each others' assembly histories even when their present-day separation is greater than thirty times the virial radius of either halo. These distances are far too large for direct interaction between the haloes to explain the correlation in their dMvir/dt. Instead, halo pairs at these distances reside in the same large-scale tidal environment, which regulates dMvir/dt for both haloes. Larger haloes are less affected by external forces, which naturally gives rise to a mass dependence of the halo conformity signal. SDSS measurements of galactic conformity exhibit a qualitatively similar dependence on stellar mass, including how the signal varies with distance. Based on the expectation that halo accretion and galaxy SFR are correlated, we predict the scale-, mass- and redshift-dependence of large-scale galactic conformity, finding that the signal should drop to undetectable levels by z ≳ 1. These predictions are testable with current surveys to z ˜ 1; confirmation would establish a strong correlation between dark matter halo accretion rate and central galaxy SFR.

Resolution 2/2004 Guidelines for the implementation of regulations for the safe transport of radioactive materials

International Nuclear Information System (INIS)

2004-01-01

This guide is intended to supplement the provisions of Resolution no. 121/2000 of the Ministry of Science Technology and Environment Regulations the Security of Radioactive Materials Transport, hereinafter Regulation, Regarding the administrative requirements for the application process Certificates of Approval for the shipments of radioactive material and for Special arrangements.

78 FR 62362 - Revisions to Procedural Regulations Governing Transportation by Intrastate Pipelines; Electronic...

Science.gov (United States)

2013-10-21

...] Revisions to Procedural Regulations Governing Transportation by Intrastate Pipelines; Electronic Tariff... under the Commission's jurisdiction pursuant to the Natural Gas Policy Act of 1978 or the Natural Gas Act.\\1\\ Take notice that, effective November 12, 2013, the list of available eTariff Type of Filing...

Novel Roles for the Insulin-Regulated Glucose Transporter-4 in Hippocampally Dependent Memory.

Science.gov (United States)

Pearson-Leary, Jiah; McNay, Ewan C

2016-11-23

The insulin-regulated glucose transporter-4 (GluT4) is critical for insulin- and contractile-mediated glucose uptake in skeletal muscle. GluT4 is also expressed in some hippocampal neurons, but its functional role in the brain is unclear. Several established molecular modulators of memory processing regulate hippocampal GluT4 trafficking and hippocampal memory formation is limited by both glucose metabolism and insulin signaling. Therefore, we hypothesized that hippocampal GluT4 might be involved in memory processes. Here, we show that, in male rats, hippocampal GluT4 translocates to the plasma membrane after memory training and that acute, selective intrahippocampal inhibition of GluT4-mediated glucose transport impaired memory acquisition, but not memory retrieval. Other studies have shown that prolonged systemic GluT4 blockade causes insulin resistance. Unexpectedly, we found that prolonged hippocampal blockade of glucose transport through GluT4-upregulated markers of hippocampal insulin signaling prevented task-associated depletion of hippocampal glucose and enhanced both working and short-term memory while also impairing long-term memory. These effects were accompanied by increased expression of hippocampal AMPA GluR1 subunits and the neuronal GluT3, but decreased expression of hippocampal brain-derived neurotrophic factor, consistent with impaired ability to form long-term memories. Our findings are the first to show the cognitive impact of brain GluT4 modulation. They identify GluT4 as a key regulator of hippocampal memory processing and also suggest differential regulation of GluT4 in the hippocampus from that in peripheral tissues. The role of insulin-regulated glucose transporter-4 (GluT4) in the brain is unclear. In the current study, we demonstrate that GluT4 is a critical component of hippocampal memory processes. Memory training increased hippocampal GluT4 translocation and memory acquisition was impaired by GluT4 blockade. Unexpectedly, whereas long

Functional properties and differential mode of regulation of the nitrate transporter from a plant symbiotic ascomycete

Science.gov (United States)

Montanini, Barbara; Viscomi, Arturo R.; Bolchi, Angelo; Martin, Yusé; Siverio, José M.; Balestrini, Raffaella; Bonfante, Paola; Ottonello, Simone

2005-01-01

Nitrogen assimilation by plant symbiotic fungi plays a central role in the mutualistic interaction established by these organisms, as well as in nitrogen flux in a variety of soils. In the present study, we report on the functional properties, structural organization and distinctive mode of regulation of TbNrt2 (Tuber borchii NRT2 family transporter), the nitrate transporter of the mycorrhizal ascomycete T. borchii. As revealed by experiments conducted in a nitrate-uptake-defective mutant of the yeast Hansenula polymorpha, TbNrt2 is a high-affinity transporter (Km=4.7 μM nitrate) that is bispecific for nitrate and nitrite. It is expressed in free-living mycelia and in mycorrhizae, where it preferentially accumulates in the plasma membrane of root-contacting hyphae. The TbNrt2 mRNA, which is transcribed from a single-copy gene clustered with the nitrate reductase gene in the T. borchii genome, was specifically up-regulated following transfer of mycelia to nitrate- (or nitrite)-containing medium. However, at variance with the strict nitrate-dependent induction commonly observed in other organisms, TbNrt2 was also up-regulated (at both the mRNA and the protein level) following transfer to a nitrogen-free medium. This unusual mode of regulation differs from that of the adjacent nitrate reductase gene, which was expressed at basal levels under nitrogen deprivation conditions and required nitrate for induction. The functional and expression properties, described in the present study, delineate TbNrt2 as a versatile transporter that may be especially suited to cope with the fluctuating (and often low) mineral nitrogen concentrations found in most natural, especially forest, soils. PMID:16201972

Understanding transporter specificity and the discrete appearance of channel-like gating domains in transporters

Directory of Open Access Journals (Sweden)

GEORGE eDIALLINAS

2014-09-01

Full Text Available Transporters are ubiquitous proteins mediating the translocation of solutes across cell membranes, a biological process involved in nutrition, signaling, neurotransmission, cell communication and drug uptake or efflux. Similarly to enzymes, most transporters have a single substrate binding-site and thus their activity follows Michaelis-Menten kinetics. Substrate binding elicits a series of structural changes, which produce a transporter conformer open towards the side opposite to the one from where the substrate was originally bound. This mechanism, involving alternate outward- and inward-facing transporter conformers, has gained significant support from structural, genetic, biochemical and biophysical approaches. Most transporters are specific for a given substrate or a group of substrates with similar chemical structure, but substrate specificity and/or affinity can vary dramatically, even among members of a transporter family that show high overall amino acid sequence and structural similarity. The current view is that transporter substrate affinity or specificity is determined by a small number of interactions a given solute can make within a specific binding site. However, genetic, biochemical and in silico modeling studies with the purine transporter UapA of the filamentous ascomycete Aspergillus nidulans have challenged this dogma. This review highlights results leading to a novel concept, stating that substrate specificity, but also transport kinetics and transporter turnover, are determined by subtle intramolecular interactions between a major substrate binding site and independent outward- or cytoplasmically-facing gating domains, analogous to those present in channels. This concept is supported by recent structural evidence from several, phylogenetically and functionally distinct transporter families. The significance of this concept is discussed in relationship to the role and potential exploitation of transporters in drug action.

Some views on the two-year review/revision cycle of the IAEA ''regulations for the safe transport of radioactive material''

International Nuclear Information System (INIS)

Fasten, C.; Nitsche, F.

2004-01-01

The ''Regulations for the Safe Transport of Radioactive Material'' of the International Atomic Energy Agency (IAEA), Vienna were last issued as a complete revised edition in 1996 as Safety Standards Series No. ST-1 [1]. A modification to this edition was made in 2000 - only in English - incorporating minor editorial corrections published as Safety Standards Series No. TS-R-1 (ST-1, Revised). Issues in French, Russian and Spanish followed shortly. A continuos review/revision process of the transport regulations was initiated in 2000 to publish an amended or a revised edition every two years. This two-year review cycle has been established to harmonise it with the review cycles of the other United Nations dangerous goods regulatory bodies, namely - the UN Committee of Experts on the Transport of Dangerous Goods, Geneva - the International Civil Aviation Organisation (ICAO), Montreal - the International Maritime Organisation (IMO), London and - the United Nations Economic Commission for Europe (UN-ECE) - Inland Transport Committee, Geneva. - Intergovernmental Organisation for International Carriage by rail (OTIF), Bern. These bodies are responsible to issue the regulations for the transport of all classes of dangerous goods (where the class 7 is ''Radioactive Material''), for the international air transport (ICAO), for the international maritime transport (IMO) and the European road, rail and inland waterway transport (UN-ECE, OTIF). The regulations of the above mentioned bodies have been published for many years within a two year period with good experience. Since 2000 the IAEA has been using the two-year cycle also. Based on this relative short time of application first experiences with this two-year cycle will be discussed

The molecular mechanism for overcoming the rate-limiting step in monoamine neurotransmitter transport

DEFF Research Database (Denmark)

Sinning, Steffen; Said, Saida; Malinauskaite, Lina

The monoamine transporter family consists of dopamine (DAT), norepinephrine (NET) and serotonin transporters (SERT) that mediate the reuptake of the monoamine neurotransmitters after their release during neurotransmission. These transporters play prominent roles in psychiatric disorders and are t......The monoamine transporter family consists of dopamine (DAT), norepinephrine (NET) and serotonin transporters (SERT) that mediate the reuptake of the monoamine neurotransmitters after their release during neurotransmission. These transporters play prominent roles in psychiatric disorders...... membrane. The rate-limiting step in monoamine reuptake is the return of the empty transporter from an inward-facing to an outward-facing conformation without neurotransmitter and sodium bound. The molecular mechanism underlying this important conformational transition has not been described. Crystal...

Splicing factor SR34b mutation reduces cadmium tolerance in Arabidopsis by regulating iron-regulated transporter 1 gene

International Nuclear Information System (INIS)

Zhang, Wentao; Du, Bojing; Liu, Di; Qi, Xiaoting

2014-01-01

Highlights: • Arabidopsis splicing factor SR34b gene is cadmium-inducible. • SR34b T-DNA insertion mutant is sensitive to cadmium due to high cadmium uptake. • SR34b is a regulator of cadmium transporter IRT1 at the posttranscription level. • These results highlight the roles of splicing factors in cadmium tolerance of plant. - Abstract: Serine/arginine-rich (SR) proteins are important splicing factors. However, the biological functions of plant SR proteins remain unclear especially in abiotic stresses. Cadmium (Cd) is a non-essential element that negatively affects plant growth and development. In this study, we provided clear evidence for SR gene involved in Cd tolerance in planta. Systemic expression analysis of 17 Arabidopsis SR genes revealed that SR34b is the only SR gene upregulated by Cd, suggesting its potential roles in Arabidopsis Cd tolerance. Consistent with this, a SR34b T-DNA insertion mutant (sr34b) was moderately sensitive to Cd, which had higher Cd 2+ uptake rate and accumulated Cd in greater amounts than wild-type. This was due to the altered expression of iron-regulated transporter 1 (IRT1) gene in sr34b mutant. Under normal growth conditions, IRT1 mRNAs highly accumulated in sr34b mutant, which was a result of increased stability of IRT1 mRNA. Under Cd stress, however, sr34b mutant plants had a splicing defect in IRT1 gene, thus reducing the IRT1 mRNA accumulation. Despite of this, sr34b mutant plants still constitutively expressed IRT1 proteins under Cd stress, thereby resulting in Cd stress-sensitive phenotype. We therefore propose the essential roles of SR34b in posttranscriptional regulation of IRT1 expression and identify it as a regulator of Arabidopsis Cd tolerance

Splicing factor SR34b mutation reduces cadmium tolerance in Arabidopsis by regulating iron-regulated transporter 1 gene

Energy Technology Data Exchange (ETDEWEB)

Zhang, Wentao; Du, Bojing; Liu, Di; Qi, Xiaoting, E-mail: qixiaoting@cnu.edu.cn

2014-12-12

Highlights: • Arabidopsis splicing factor SR34b gene is cadmium-inducible. • SR34b T-DNA insertion mutant is sensitive to cadmium due to high cadmium uptake. • SR34b is a regulator of cadmium transporter IRT1 at the posttranscription level. • These results highlight the roles of splicing factors in cadmium tolerance of plant. - Abstract: Serine/arginine-rich (SR) proteins are important splicing factors. However, the biological functions of plant SR proteins remain unclear especially in abiotic stresses. Cadmium (Cd) is a non-essential element that negatively affects plant growth and development. In this study, we provided clear evidence for SR gene involved in Cd tolerance in planta. Systemic expression analysis of 17 Arabidopsis SR genes revealed that SR34b is the only SR gene upregulated by Cd, suggesting its potential roles in Arabidopsis Cd tolerance. Consistent with this, a SR34b T-DNA insertion mutant (sr34b) was moderately sensitive to Cd, which had higher Cd{sup 2+} uptake rate and accumulated Cd in greater amounts than wild-type. This was due to the altered expression of iron-regulated transporter 1 (IRT1) gene in sr34b mutant. Under normal growth conditions, IRT1 mRNAs highly accumulated in sr34b mutant, which was a result of increased stability of IRT1 mRNA. Under Cd stress, however, sr34b mutant plants had a splicing defect in IRT1 gene, thus reducing the IRT1 mRNA accumulation. Despite of this, sr34b mutant plants still constitutively expressed IRT1 proteins under Cd stress, thereby resulting in Cd stress-sensitive phenotype. We therefore propose the essential roles of SR34b in posttranscriptional regulation of IRT1 expression and identify it as a regulator of Arabidopsis Cd tolerance.

Conformal Infinity

Directory of Open Access Journals (Sweden)

Frauendiener Jörg

2000-08-01

Full Text Available The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, ``conformal infinity'' is related with almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved out of physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation and how it lends itself very naturally to solve radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

Conformal Infinity.

Science.gov (United States)

Frauendiener, Jörg

2004-01-01

The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, "conformal infinity" is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

The ICRP 60 and the agency's regulations for the safe transport of radioactive material

International Nuclear Information System (INIS)

Biaggio, A.L.; Novo, R.G.

1993-01-01

The International Commission on Radiological Protection (ICRP) has adopted its new '1990 Recommendations of the International Commission on Radiological Protection' in November 1990, they were published in 1991 as 'ICRP Publication 60.' Two main scenarios are considered by the new ICRP's recommendations: a) Protection in proposed and continuing practices (further subdivided as protection against actual exposures and protection against potential exposures); and b) Protection by intervention. Although intervention means any activity in order to decrease the overall exposure, removing existing sources, modifying pathways or reducing the number of exposed individuals, in relation to the transport of radioactive materials, protection by intervention is related mainly to emergency planning, while protection against actual and potential exposures can be considered as the subject of most of the requirements of the 'Regulations for the Safe Transport of Radioactive Material', of the International Atomic Energy Agency (IAEA). The on-going revision of the IAEA Safety Series No. 9, which is aimed at putting this publication in line with the new ICRP recommendations will, for the first time, provide a convalidated radiological framework for the 1996 revision of the Agency Transport Regulations. However, to adapt to the transport area the radiological principles and criteria will require a significant effort and a carefully evaluation of the overall impact of each change proposed. (J.P.N.)

Transport of radioactive material by air, proposal for a revision of the regulation

International Nuclear Information System (INIS)

Devillers, C.; Ringot, C.

1989-01-01

The regulation should be modified in such a way that the packages used for the air transport of radioactive material presenting a high level of potential danger be designed to fulfill their safety functions for a large fraction of the conditions likely to be encountered in an aircraft accident

Astrocytic GABA Transporters

DEFF Research Database (Denmark)

Schousboe, Arne; Wellendorph, Petrine; Frølund, Bente

2017-01-01

, and several of these compounds have been shown to exhibit pronounced anticonvulsant activity in a variety of animal seizure models. As proof of concept of the validity of this drug development approach, one GABA-transport inhibitor, tiagabine, has been developed as a clinically active antiepileptic drug......Inactivation of GABA-mediated neurotransmission is achieved by high-affinity transporters located at both GABAergic neurons and the surrounding astrocytes. Early studies of the pharmacological properties of neuronal and glial GABA transporters suggested that different types of transporters might...... be expressed in the two cell types, and such a scenario was confirmed by the cloning of four distinctly different GABA transporters from a number of different species. These GABA-transport entities have been extensively characterized using a large number of GABA analogues of restricted conformation...

Regulation of ion transport via apical purinergic receptors in intact rabbit airway epithelium

DEFF Research Database (Denmark)

Poulsen, Asser Nyander; Klausen, Thomas Levin; Pedersen, Peter Steen

2005-01-01

and unidirectional Cl- fluxes decreased significantly. The results suggest that nucleotides released to the airway surface liquid exert an autocrine regulation of epithelial NaCl absorption mainly by inhibiting the amiloride-sensitive epithelial Na+ channel (ENaC) and paracellular anion conductance via a P2Y......We investigated purinergic receptors involved in ion transport regulation in the intact rabbit nasal airway epithelium. Stimulation of apical membrane P2Y receptors with ATP or UTP (200 microM) induced transient increases in short-circuit current (Isc) of 13 and 6% followed by sustained inhibitions...

A study of signalling events regulating the retrograde axonal transport of neurotrophic factors in vivo

International Nuclear Information System (INIS)

Reynolds, A.J.; Bartlett, S.E.; Hendry, I.A.

1998-01-01

Full text: Soluble neurotrophic factors such as NGF promote the survival of sympathetic and sensory neuronal populations by binding to receptors present on the nerve terminal and transported to the cell body. This study aimed to establish the molecular mechanisms regulating this process by identifying potential signalling molecules that may be involved using specific pharmacological inhibitors. Adult Balb/c or CBA mice were anaesthetized using 88 μg/g ketamine and 16 μg/g rompun (i.p.) and 1 μl containing 4 μCi of 125 I-labelled NT-3 (37 ng) or pNGF (22 ng) was co-injected with inhibitors into the anterior eye chamber. After 20 hours the accumulated radioactivity was measured in the superior cervical and trigeminal ganglia. The PI3-kinase inhibitor Wortmannin inhibited 125 I-NT-3 transport in the range of 0.1-1 nmol/eye as previously shown with 125 I-βOeGF. The cPLA 2 inhibitor AACOCF3 did not significantly affect the retrograde transport of either 125 I-NT-3 or 125 I-βNGF suggesting that Wortmannin is not influencing the transport of these neurotrophins by inhibiting cPLA 2 activity. The dynein ATPase inhibitor erythro-9-[3-(2-hydroxynonyl)]adenine (1 mM) also selectively reduced 125 I-βNGF transport. Non-specific tyrosine kinase inhibitors did not have a significant effect. These results further suggest that PI3-kinase might regulate the intracellular transport of neurotrophic factors, and that retrograde axonal transport of these proteins relies on the dynein motor protein in vivo. Copyright (1998) Australian Neuroscience Society

Transport mechanisms and their pathology-induced regulation govern tyrosine kinase inhibitor delivery in rheumatoid arthritis.

Directory of Open Access Journals (Sweden)

Christian Schmidt-Lauber

Full Text Available BACKGROUND: Tyrosine kinase inhibitors (TKIs are effective in treating malignant disorders and were lately suggested to have an impact on non-malignant diseases. However, in some inflammatory conditions like rheumatoid arthritis (RA the in vivo effect seemed to be moderate. As most TKIs are taken up actively into cells by cell membrane transporters, this study aimed to evaluate the role of such transporters for the accumulation of the TKI Imatinib mesylates in RA synovial fibroblasts as well as their regulation under inflammatory conditions. METHODOLOGY/PRINCIPAL FINDINGS: The transport and accumulation of Imatinib was investigated in transporter-transfected HEK293 cells and human RA synovial fibroblasts (hRASF. Transporter expression was quantified by qRT-PCR. In transfection experiments, hMATE1 showed the highest apparent affinity for Imatinib among all known Imatinib transporters. Experiments quantifying the Imatinib uptake in the presence of specific transporter inhibitors and after siRNA knockdown of hMATE1 indeed identified hMATE1 to mediate Imatinib transport in hRASF. The anti-proliferative effect of Imatinib on PDGF stimulated hRASF was quantified by cell counting and directly correlated with the uptake activity of hMATE1. Expression of hMATE1 was investigated by Western blot and immuno-fluorescence. Imatinib transport under disease-relevant conditions, such as an altered pH and following stimulation with different cytokines, was also investigated by HPLC. The uptake was significantly reduced by an acidic extracellular pH as well as by the cytokines TNFα, IL-1β and IL-6, which all decreased the expression of hMATE1-mRNA and protein. CONCLUSION/SIGNIFICANCE: The regulation of Imatinib uptake via hMATE1 in hRASF and resulting effects on their proliferation may explain moderate in vivo effects on RA. Moreover, our results suggest that investigating transporter mediated drug processing under normal and pathological conditions is important

A conformational restriction approach to the development of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease.

Science.gov (United States)

Toda, Narihiro; Tago, Keiko; Marumoto, Shinji; Takami, Kazuko; Ori, Mayuko; Yamada, Naho; Koyama, Kazuo; Naruto, Shunji; Abe, Kazumi; Yamazaki, Reina; Hara, Takao; Aoyagi, Atsushi; Abe, Yasuyuki; Kaneko, Tsugio; Kogen, Hiroshi

2003-10-01

Alzheimer's disease (AD) has been treated with acetylcholinesterase (AChE) inhibitors such as donepezil. However, the clinical usefulness of AChE inhibitors is limited mainly due to their adverse peripheral effects. Depression seen in AD patients has been treated with serotonin transporter (SERT) inhibitors. We considered that combining SERT and AChE inhibition could improve the clinical usefulness of AChE inhibitors. In a previous paper, we found a potential dual inhibitor, 1, of AChE (IC50=101 nM) and SERT (IC50=42 nM), but its AChE inhibition activity was less than donepezil (IC50=10 nM). Here, we report the conformationally restricted (R)-18a considerably enhanced inhibitory activity against AChE (IC50=14 nM) and SERT (IC50=6 nM).

Probing the conformation of a conserved glutamic acid within the Cl- pathway of a CLC H+/Cl- exchanger.

Science.gov (United States)

Vien, Malvin; Basilio, Daniel; Leisle, Lilia; Accardi, Alessio

2017-04-03

The CLC proteins form a broad family of anion-selective transport proteins that includes both channels and exchangers. Despite extensive structural, functional, and computational studies, the transport mechanism of the CLC exchangers remains poorly understood. Several transport models have been proposed but have failed to capture all the key features of these transporters. Multiple CLC crystal structures have suggested that a conserved glutamic acid, Glu ex , can adopt three conformations and that the interconversion of its side chain between these states underlies H + /Cl - exchange. One of these states, in which Glu ex occupies the central binding site (S cen ) while Cl - ions fill the internal and external sites (S int and S ext ), has only been observed in one homologue, the eukaryotic cmCLC. The existence of such a state in other CLCs has not been demonstrated. In this study, we find that during transport, the prototypical prokaryotic CLC exchanger, CLC-ec1, adopts a conformation with functional characteristics that match those predicted for a cmCLC-like state, with Glu ex trapped in S cen between two Cl - ions. Transport by CLC-ec1 is reduced when [Cl - ] is symmetrically increased on both sides of the membrane and mutations that disrupt the hydrogen bonds stabilizing Glu ex in S cen destabilize this trapped state. Furthermore, inhibition of transport by high [Cl - ] is abolished in the E148A mutant, in which the Glu ex side chain is removed. Collectively, our results suggest that, during the CLC transport cycle, Glu ex can occupy S cen as well as the S ext position in which it has been captured crystallographically and that hydrogen bonds with the side chains of residues that coordinate ion binding to S cen play a role in determining the equilibrium between these two conformations. © 2017 Vien et al.

Probing the conformation of a conserved glutamic acid within the Cl− pathway of a CLC H+/Cl− exchanger

Science.gov (United States)

Vien, Malvin

2017-01-01

The CLC proteins form a broad family of anion-selective transport proteins that includes both channels and exchangers. Despite extensive structural, functional, and computational studies, the transport mechanism of the CLC exchangers remains poorly understood. Several transport models have been proposed but have failed to capture all the key features of these transporters. Multiple CLC crystal structures have suggested that a conserved glutamic acid, Gluex, can adopt three conformations and that the interconversion of its side chain between these states underlies H+/Cl− exchange. One of these states, in which Gluex occupies the central binding site (Scen) while Cl− ions fill the internal and external sites (Sint and Sext), has only been observed in one homologue, the eukaryotic cmCLC. The existence of such a state in other CLCs has not been demonstrated. In this study, we find that during transport, the prototypical prokaryotic CLC exchanger, CLC-ec1, adopts a conformation with functional characteristics that match those predicted for a cmCLC-like state, with Gluex trapped in Scen between two Cl− ions. Transport by CLC-ec1 is reduced when [Cl−] is symmetrically increased on both sides of the membrane and mutations that disrupt the hydrogen bonds stabilizing Gluex in Scen destabilize this trapped state. Furthermore, inhibition of transport by high [Cl−] is abolished in the E148A mutant, in which the Gluex side chain is removed. Collectively, our results suggest that, during the CLC transport cycle, Gluex can occupy Scen as well as the Sext position in which it has been captured crystallographically and that hydrogen bonds with the side chains of residues that coordinate ion binding to Scen play a role in determining the equilibrium between these two conformations. PMID:28246117

The zinc transporter ZIPT-7.1 regulates sperm activation in nematodes.

Directory of Open Access Journals (Sweden)

Yanmei Zhao

2018-06-01

Full Text Available Sperm activation is a fascinating example of cell differentiation, in which immotile spermatids undergo a rapid and dramatic transition to become mature, motile sperm. Because the sperm nucleus is transcriptionally silent, this transition does not involve transcriptional changes. Although Caenorhabditis elegans is a leading model for studies of sperm activation, the mechanisms by which signaling pathways induce this transformation remain poorly characterized. Here we show that a conserved transmembrane zinc transporter, ZIPT-7.1, regulates the induction of sperm activation in Caenorhabditis nematodes. The zipt-7.1 mutant hermaphrodites cannot self-fertilize, and males reproduce poorly, because mutant spermatids are defective in responding to activating signals. The zipt-7.1 gene is expressed in the germ line and functions in germ cells to promote sperm activation. When expressed in mammalian cells, ZIPT-7.1 mediates zinc transport with high specificity and is predominantly located on internal membranes. Finally, genetic epistasis places zipt-7.1 at the end of the spe-8 sperm activation pathway, and ZIPT-7.1 binds SPE-4, a presenilin that regulates sperm activation. Based on these results, we propose a new model for sperm activation. In spermatids, inactive ZIPT-7.1 is localized to the membranous organelles, which contain higher levels of zinc than the cytoplasm. When sperm activation is triggered, ZIPT-7.1 activity increases, releasing zinc from internal stores. The resulting increase in cytoplasmic zinc promotes the phenotypic changes characteristic of activation. Thus, zinc signaling is a key step in the signal transduction process that mediates sperm activation, and we have identified a zinc transporter that is central to this activation process.

Characterization and regulation of glycine transport in Fusarium oxysporum var. lini.

Science.gov (United States)

Castro, I M; Lima, A A; Nascimento, A F; Ruas, M M; Nicoli, J R; Brandão, R L

1996-08-01

Glycine was transported in Fusarium oxysporum cells, grown on glycine as the sole source of carbon and nitrogen, by a facilitated diffusion transport system with a half-saturation constant (Ks) of 11 mM and a maximum velocity (Vmax) of 1.2 mM (g dry weight)-1 h-1 at pH 5.0 and 26 degrees C. Under conditions of nitrogen starvation, the same system was present together with a high-affinity one (Ks) of about 47 microM and Vmax of about 60 microM (g dry weight)-1 h-1). The low-affinity system was more specific than the high-affinity system. Cells grown on gelatine showed the same behavior. In cells grown on glucose-gelatine medium, the low-affinity system was poorly expressed even after carbon and nitrogen starvation. Moreover, addition of glucose to cells grown on glycine and resuspended in mineral medium caused an increase of the glycine transport probably due to a boost in protein synthesis. This stimulation did not affect the Ks of the low-affinity system. These results demonstrate that, as is the case for other eukaryotic systems, F. oxysporum glycine transport is under control of nitrogen sources but its regulation by carbon sources appears to be more complex.

Regulated bioanalysis of conformers - A case study with ASP2151 in dog plasma and urine.

Science.gov (United States)

Ohtsu, Yoshiaki; Otsuka, Shohei; Nakamura, Takeshi; Noguchi, Kiyoshi

2015-08-01

We developed and validated bioanalytical methods for a potent helicase-primase inhibitor ASP2151 that has two conformers. These conformers elute as unseparated broad peaks under ordinary high-performance liquid chromatographic conditions, indicating discernable differences in hydrophobicity. We observed that column temperature and mobile phase pH have no effect on these peaks and that conformers form a single symmetrical peak when tetrahydrofuran is added to the mobile phase. In addition, we needed to develop semi-automated methods where inter-conversion of the conformers is unlikely to cause sample-to-sample extraction variability. Briefly, following the addition of deuterium-labeled ASP2151 as an internal standard (IS), dog plasma samples or acetonitrile-added urine samples were filtrated. The filtrates were then injected into a column-switching liquid chromatography-tandem mass spectrometry (LC-MS/MS) system and trapped onto an extraction column. Extracts were back-flushed onto an analytical C18 column (4.6×50mm, 3μm) with a mobile phase consisting of methanol, tetrahydrofuran, and 20mmol/L ammonium acetate (45:5:50, v/v/v). The eluent was monitored in the negative atmospheric pressure chemical ionization mode. The calibration curve was linear over a range of 5-1000ng/mL for plasma and 0.5-100μg/mL for urine. Validation data met the acceptance criteria in accordance with regulatory guidance and demonstrated that these methods were selective, accurate, and reproducible. In addition, the present methods were successfully applied to a pharmacokinetic study in dogs. Copyright © 2015 Elsevier B.V. All rights reserved.

Conformal Infinity

Directory of Open Access Journals (Sweden)

Frauendiener Jörg

2004-01-01

Full Text Available The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, 'conformal infinity' is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

Decree 560/003. It approve the National Regulations text about dangerous goods transport by road, for national jurisdiction routes

International Nuclear Information System (INIS)

2004-01-01

This decree approve the transport regulation in the national jurisdiction routes. Is prohibited the transport of dangerous good with contamination risk in food, medication or articles intended for human or animal use

Radioactive material air transportation; Transporte aereo de material radioativo

Energy Technology Data Exchange (ETDEWEB)

Pader y Terry, Claudio Cosme [Varig Logistica (VARIGLOG), Sao Paulo, SP (Brazil)

2002-07-01

As function of the high aggregated value, safety regulations and the useful life time, the air transportation has been used more regularly because is fast, reliable, and by giving great security to the cargo. Based on the International Atomic Energy Agency (IAEA), the IATA (International Air Transportation Association) has reproduced in his dangerous goods manual (Dangerous Goods Regulations - DGR IATA), the regulation for the radioactive material air transportation. Those documents support this presentation.

Logarithmic conformal field theory through nilpotent conformal dimensions

International Nuclear Information System (INIS)

Moghimi-Araghi, S.; Rouhani, S.; Saadat, M.

2001-01-01

We study logarithmic conformal field theories (LCFTs) through the introduction of nilpotent conformal weights. Using this device, we derive the properties of LCFTs such as the transformation laws, singular vectors and the structure of correlation functions. We discuss the emergence of an extra energy momentum tensor, which is the logarithmic partner of the energy momentum tensor

Viscous conformal gauge theories

DEFF Research Database (Denmark)

Toniato, Arianna; Sannino, Francesco; Rischke, Dirk H.

2017-01-01

We present the conformal behavior of the shear viscosity-to-entropy density ratio and the fermion-number diffusion coefficient within the perturbative regime of the conformal window for gauge-fermion theories.......We present the conformal behavior of the shear viscosity-to-entropy density ratio and the fermion-number diffusion coefficient within the perturbative regime of the conformal window for gauge-fermion theories....

National competent authorities. List no. 11. Regulations for the safe transport of radioactive materials. 1973 revised edition (Safety series no. 6)

International Nuclear Information System (INIS)

1979-04-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness

National competent authorities. List no. 11. Regulations for the safe transport of radioactive materials. 1973 revised edition (Safety series no. 6)

Energy Technology Data Exchange (ETDEWEB)

NONE

1979-04-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness.

National competent authorities. List no. 10. Regulations for the safe transport of radioactive materials. 1973 revised edition (Safety series no. 6)

Energy Technology Data Exchange (ETDEWEB)

NONE

1978-04-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness.

National competent authorities. List no. 9. Regulations for the safe transport of radioactive materials. 1973 revised edition (Safety series no. 6)

Energy Technology Data Exchange (ETDEWEB)

NONE

1977-08-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness.

National competent authorities. List no. 7. Regulations for the safe transport of radioactive materials. 1973 revised edition (Safety series no. 6)

Energy Technology Data Exchange (ETDEWEB)

NONE

1975-01-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness.

National competent authorities. List no. 6. Regulations for the safe transport of radioactive materials. 1973 revised edition (Safety series no. 6)

Energy Technology Data Exchange (ETDEWEB)

NONE

1974-01-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness.

National competent authorities. List no. 8. Regulations for the safe transport of radioactive materials. 1973 revised edition (Safety series no. 6)

International Nuclear Information System (INIS)

1976-01-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness

National competent authorities. List no. 10. Regulations for the safe transport of radioactive materials. 1973 revised edition (Safety series no. 6)

International Nuclear Information System (INIS)

1978-04-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness

National competent authorities. List no. 7. Regulations for the safe transport of radioactive materials. 1973 revised edition (Safety series no. 6)

International Nuclear Information System (INIS)

1975-01-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness

National competent authorities. List no. 9. Regulations for the safe transport of radioactive materials. 1973 revised edition (Safety series no. 6)

International Nuclear Information System (INIS)

1977-08-01

Any national or international authority designated or otherwise recognised as such for any purpose in connection with the transport Regulations is known as a competent authority. In the Member States such a body has the responsibility for establishing national legislation to bring the Agency's transport Regulations into effect and for assuring compliance with its requirements. Depending on the national regulatory or institutional framework the functions of the competent authority may be assigned to one or more bodies. To assist Member States in implementing the transport Regulations and carrying out responsibility for compliance assurance, the IAEA continues to maintain this updated list of designated national competent authorities. Member States are annually requested to verify the list for correctness and completeness

National competent authorities. List no. 6. Regulations for the safe transport of radioactive materials. 1973 revised edition (Safety series no. 6)