Metabolite Regulation of Nuclear Localization of Carbohydrate-response Element-binding Protein (ChREBP)

PubMed Central

Sato, Shogo; Jung, Hunmin; Nakagawa, Tsutomu; Pawlosky, Robert; Takeshima, Tomomi; Lee, Wan-Ru; Sakiyama, Haruhiko; Laxman, Sunil; Wynn, R. Max; Tu, Benjamin P.; MacMillan, John B.; De Brabander, Jef K.; Veech, Richard L.; Uyeda, Kosaku

2016-01-01

The carbohydrate-response element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays an essential role in converting excess carbohydrate to fat storage in the liver. In response to glucose levels, ChREBP is regulated by nuclear/cytosol trafficking via interaction with 14-3-3 proteins, CRM-1 (exportin-1 or XPO-1), or importins. Nuclear localization of ChREBP was rapidly inhibited when incubated in branched-chain α-ketoacids, saturated and unsaturated fatty acids, or 5-aminoimidazole-4-carboxamide ribonucleotide. Here, we discovered that protein-free extracts of high fat-fed livers contained, in addition to ketone bodies, a new metabolite, identified as AMP, which specifically activates the interaction between ChREBP and 14-3-3. The crystal structure showed that AMP binds directly to the N terminus of ChREBP-α2 helix. Our results suggest that AMP inhibits the nuclear localization of ChREBP through an allosteric activation of ChREBP/14-3-3 interactions and not by activation of AMPK. AMP and ketone bodies together can therefore inhibit lipogenesis by restricting localization of ChREBP to the cytoplasm during periods of ketosis. PMID:26984404

Adenylyl cyclase A expression is tip-specific in Dictyostelium slugs and directs StatA nuclear translocation and CudA gene expression.

PubMed

Verkerke-van Wijk, I; Fukuzawa, M; Devreotes, P N; Schaap, P

2001-06-01

cAMP oscillations, generated by adenylyl cyclase A (ACA), coordinate cell aggregation in Dictyostelium and have also been implicated in organizer function during multicellular development. We used a gene fusion of the ACA promoter with a labile lacZ derivative to study the expression pattern of ACA. During aggregation, most cells expressed ACA, but thereafter expression was lost in all cells except those of the anterior tip. Before aggregation, ACA transcription was strongly upregulated by nanomolar cAMP pulses. Postaggregative transcription was sustained by nanomolar cAMP pulses, but downregulated by a continuous micromolar cAMP stimulus and by the stalk-cell-inducing factor DIF. Earlier work showed that the transcription factor StatA displays tip-specific nuclear translocation and directs tip-specific expression of the nuclear protein CudA, which is essential for culmination. Both StatA and CudA were present in nuclei throughout the entire slug in an aca null mutant that expresses ACA from the constitutive actin15 promoter. This suggests that the tip-specific expression of ACA directs tip-specific nuclear translocation of StatA and tip-specific expression of CudA. Copyright 2001 Academic Press.

Increasing the cAMP concentration during in vitro maturation of pig oocytes improves cumulus maturation and subsequent fertilization in vitro.

PubMed

Appeltant, R; Beek, J; Vandenberghe, L; Maes, D; Van Soom, A

2015-02-01

Porcine IVF faces various problems such as incomplete cytoplasmic maturation of the oocyte and polyspermy. Previous studies proved the importance of cAMP in regulating nuclear and cytoplasmic maturation of oocytes. This study investigated the effect of the cAMP-modulating agents 3-isobutyl-1-methylxanthine (IBMX) and dibutyryl cAMP sodium salt (dbcAMP) on several parameters during in vitro production of porcine embryos. First, we wanted to see if oocyte collection in IBMX could meiotically arrest oocytes and, as such, improve synchronization of nuclear and cytoplasmic maturation. To this end, cumulus-oocyte complexes (COCs) were collected from gilts in HEPES-buffered Tyrode balanced salt solution medium with 0.5-mM IBMX or without IBMX. At the end of oocyte collection, the effect of IBMX on chromatin configuration was evaluated. However, no differences could be observed in nuclear configuration between IBMX- and IBMX+ oocytes (P > 0.05). Second, we added dbcAMP during IVM to improve cytoplasmic maturation and evaluated cumulus expansion (lack of adhesion), a disintegrin and metalloproteinase with thrombospondin-like repeats (ADAMTS-1) levels in cumulus cells, fertilization, and blastocyst rates. Cumulus-oocyte complexes were matured in modified North Carolina State University medium 37 with or without 1-mM dbcAMP. Frozen-thawed, epididymal, boar spermatozoa were used for IVF. After IVF, presumed zygotes were cultured for 7 days in North Carolina State University medium 23. Penetration rate decreased in dbcAMP+ (57.3%) compared with dbcAMP- (67.8%), but the polyspermy rate also decreased (43.3% vs. 53.4%, respectively) leading to an increased normal fertilization rate (56.7% vs. 46.6%, respectively; P < 0.05). Only 7.2% of the COCs showed adhesion in dbcAMP+ which was lower than 15.7% in dbcAMP- (P < 0.05) probably because of an upregulation of the ADAMTS-1 protein by dbcAMP. When the adherent oocytes were removed during maturation, no difference could be detected between the blastocyst rate of dbcAMP- and dbcAMP+ (17.1% and 21.0% on Day 7, respectively; P > 0.05). In conclusion, the use of IBMX during collection did not cause a meiotic arrest. Using dbcAMP during IVM caused a greater normal fertilization rate, a lower rate of adherent COCs during IVM, higher levels of ADAMTS-1 in cumulus cells, and an equal blastocyst rate after screening out adherent COCs. These findings contribute to a better understanding of cAMP involvement in porcine oocyte maturation and provide a basis to develop an improved system with less polyspermy and higher blastocyst rates. Copyright © 2015 Elsevier Inc. All rights reserved.

An integrable family of Monge-Ampère equations and their multi-Hamiltonian structure

NASA Astrophysics Data System (ADS)

Nutku, Y.; Sarioǧlu, Ö.

1993-02-01

We have identified a completely integrable family of Monge-Ampère equations through an examination of their Hamiltonian structure. Starting with a variational formulation of the Monge-Ampère equations we have constructed the first Hamiltonian operator through an application of Dirac's theory of constraints. The completely integrable class of Monge-Ampère equations are then obtained by solving the Jacobi identities for a sufficiently general form of the second Hamiltonian operator that is compatible with the first.

Lattice QCD Calculations in Nuclear Physics towards the Exascale

NASA Astrophysics Data System (ADS)

Joo, Balint

2017-01-01

The combination of algorithmic advances and new highly parallel computing architectures are enabling lattice QCD calculations to tackle ever more complex problems in nuclear physics. In this talk I will review some computational challenges that are encountered in large scale cold nuclear physics campaigns such as those in hadron spectroscopy calculations. I will discuss progress in addressing these with algorithmic improvements such as multi-grid solvers and software for recent hardware architectures such as GPUs and Intel Xeon Phi, Knights Landing. Finally, I will highlight some current topics for research and development as we head towards the Exascale era This material is funded by the U.S. Department of Energy, Office Of Science, Offices of Nuclear Physics, High Energy Physics and Advanced Scientific Computing Research, as well as the Office of Nuclear Physics under contract DE-AC05-06OR23177.

Sandia National Laboratories: National Security Missions: Nuclear Weapons:

Science.gov Websites

Safety & Security Sandia National Laboratories Exceptional service in the national interest & Figures Programs Nuclear Weapons About Nuclear Weapons Safety & Security Weapons Science & Twitter YouTube Flickr RSS Top Nuclear Weapons About Nuclear Weapons at Sandia Safety & Security

Control of cytoplasmic and nuclear protein kinase A by phosphodiesterases and phosphatases in cardiac myocytes

PubMed Central

Haj Slimane, Zeineb; Bedioune, Ibrahim; Lechêne, Patrick; Varin, Audrey; Lefebvre, Florence; Mateo, Philippe; Domergue-Dupont, Valérie; Dewenter, Matthias; Richter, Wito; Conti, Marco; El-Armouche, Ali; Zhang, Jin; Fischmeister, Rodolphe; Vandecasteele, Grégoire

2014-01-01

Aims The cAMP-dependent protein kinase (PKA) mediates β-adrenoceptor (β-AR) regulation of cardiac contraction and gene expression. Whereas PKA activity is well characterized in various subcellular compartments of adult cardiomyocytes, its regulation in the nucleus remains largely unknown. The aim of the present study was to compare the modalities of PKA regulation in the cytoplasm and nucleus of cardiomyocytes. Methods and results Cytoplasmic and nuclear cAMP and PKA activity were measured with targeted fluorescence resonance energy transfer probes in adult rat ventricular myocytes. β-AR stimulation with isoprenaline (Iso) led to fast cAMP elevation in both compartments, whereas PKA activity was fast in the cytoplasm but markedly slower in the nucleus. Iso was also more potent and efficient in activating cytoplasmic than nuclear PKA. Similar slow kinetics of nuclear PKA activation was observed upon adenylyl cyclase activation with L-858051 or phosphodiesterase (PDE) inhibition with 3-isobutyl-1-methylxantine. Consistently, pulse stimulation with Iso (15 s) maximally induced PKA and myosin-binding protein C phosphorylation in the cytoplasm, but marginally activated PKA and cAMP response element-binding protein phosphorylation in the nucleus. Inhibition of PDE4 or ablation of the Pde4d gene in mice prolonged cytoplasmic PKA activation and enhanced nuclear PKA responses. In the cytoplasm, phosphatase 1 (PP1) and 2A (PP2A) contributed to the termination of PKA responses, whereas only PP1 played a role in the nucleus. Conclusion Our study reveals a differential integration of cytoplasmic and nuclear PKA responses to β-AR stimulation in cardiac myocytes. This may have important implications in the physiological and pathological hypertrophic response to β-AR stimulation. PMID:24550350

IP{sub 3}-dependent intracellular Ca{sup 2+} release is required for cAMP-induced c-fos expression in hippocampal neurons

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

Zhang, Wenting; Tingare, Asmita; Ng, David Chi-Heng

2012-08-24

Highlights: Black-Right-Pointing-Pointer cAMP-induced c-fos expression in hippocampal neurons requires a submembraneous Ca{sup 2+} pool. Black-Right-Pointing-Pointer The submembraneous Ca{sup 2+} pool derives from intracellular ER stores. Black-Right-Pointing-Pointer Expression of IP{sub 3}-metabolizing enzymes inhibits cAMP-induced c-fos expression. Black-Right-Pointing-Pointer SRE-mediated and CRE-mediated gene expression is sensitive to IP{sub 3}-metabolizing enzymes. Black-Right-Pointing-Pointer Intracellular Ca{sup 2+} release is required for cAMP-induced nuclear translocation of TORC1. -- Abstract: Ca{sup 2+} and cAMP are widely used in concert by neurons to relay signals from the synapse to the nucleus, where synaptic activity modulates gene expression required for synaptic plasticity. Neurons utilize different transcriptional regulators to integrate informationmore » encoded in the spatiotemporal dynamics and magnitude of Ca{sup 2+} and cAMP signals, including some that are Ca{sup 2+}-responsive, some that are cAMP-responsive and some that detect coincident Ca{sup 2+} and cAMP signals. Because Ca{sup 2+} and cAMP can influence each other's amplitude and spatiotemporal characteristics, we investigated how cAMP acts to regulate gene expression when increases in intracellular Ca{sup 2+} are buffered. We show here that cAMP-mobilizing stimuli are unable to induce expression of the immediate early gene c-fos in hippocampal neurons in the presence of the intracellular Ca{sup 2+} buffer BAPTA-AM. Expression of enzymes that attenuate intracellular IP{sub 3} levels also inhibited cAMP-dependent c-fos induction. Synaptic activity induces c-fos transcription through two cis regulatory DNA elements - the CRE and the SRE. We show here that in response to cAMP both CRE-mediated and SRE-mediated induction of a luciferase reporter gene is attenuated by IP{sub 3} metabolizing enzymes. Furthermore, cAMP-induced nuclear translocation of the CREB coactivator TORC1 was inhibited by depletion of intracellular Ca{sup 2+} stores. Our data indicate that Ca{sup 2+} release from IP{sub 3}-sensitive pools is required for cAMP-induced transcription in hippocampal neurons.« less

Sandia National Laboratories: National Security Programs

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Protein kinase A is part of a mechanism that regulates nuclear reimport of the nuclear tRNA export receptors Los1p and Msn5p.

PubMed

Pierce, Jacqueline B; van der Merwe, George; Mangroo, Dev

2014-02-01

The two main signal transduction mechanisms that allow eukaryotes to sense and respond to changes in glucose availability in the environment are the cyclic AMP (cAMP)/protein kinase A (PKA) and AMP-activated protein kinase (AMPK)/Snf1 kinase-dependent pathways. Previous studies have shown that the nuclear tRNA export process is inhibited in Saccharomyces cerevisiae deprived of glucose. However, the signal transduction pathway involved and the mechanism by which glucose availability regulates nuclear-cytoplasmic tRNA trafficking are not understood. Here, we show that inhibition of nuclear tRNA export is caused by a block in nuclear reimport of the tRNA export receptors during glucose deprivation. Cytoplasmic accumulation of the tRNA export receptors during glucose deprivation is not caused by activation of Snf1p. Evidence obtained suggests that PKA is part of the mechanism that regulates nuclear reimport of the tRNA export receptors in response to glucose availability. This mechanism does not appear to involve phosphorylation of the nuclear tRNA export receptors by PKA. The block in nuclear reimport of the tRNA export receptors appears to be caused by activation of an unidentified mechanism when PKA is turned off during glucose deprivation. Taken together, the data suggest that PKA facilitates return of the tRNA export receptors to the nucleus by inhibiting an unidentified activity that facilitates cytoplasmic accumulation of the tRNA export receptors when glucose in the environment is limiting. A PKA-independent mechanism was also found to regulate nuclear tRNA export in response to glucose availability. This mechanism, however, does not regulate nuclear reimport of the tRNA export receptors.

Protein Kinase A Is Part of a Mechanism That Regulates Nuclear Reimport of the Nuclear tRNA Export Receptors Los1p and Msn5p

PubMed Central

Pierce, Jacqueline B.; van der Merwe, George

2014-01-01

The two main signal transduction mechanisms that allow eukaryotes to sense and respond to changes in glucose availability in the environment are the cyclic AMP (cAMP)/protein kinase A (PKA) and AMP-activated protein kinase (AMPK)/Snf1 kinase-dependent pathways. Previous studies have shown that the nuclear tRNA export process is inhibited in Saccharomyces cerevisiae deprived of glucose. However, the signal transduction pathway involved and the mechanism by which glucose availability regulates nuclear-cytoplasmic tRNA trafficking are not understood. Here, we show that inhibition of nuclear tRNA export is caused by a block in nuclear reimport of the tRNA export receptors during glucose deprivation. Cytoplasmic accumulation of the tRNA export receptors during glucose deprivation is not caused by activation of Snf1p. Evidence obtained suggests that PKA is part of the mechanism that regulates nuclear reimport of the tRNA export receptors in response to glucose availability. This mechanism does not appear to involve phosphorylation of the nuclear tRNA export receptors by PKA. The block in nuclear reimport of the tRNA export receptors appears to be caused by activation of an unidentified mechanism when PKA is turned off during glucose deprivation. Taken together, the data suggest that PKA facilitates return of the tRNA export receptors to the nucleus by inhibiting an unidentified activity that facilitates cytoplasmic accumulation of the tRNA export receptors when glucose in the environment is limiting. A PKA-independent mechanism was also found to regulate nuclear tRNA export in response to glucose availability. This mechanism, however, does not regulate nuclear reimport of the tRNA export receptors. PMID:24297441

OECD-NEA Expert Group on Multi-Physics Experimental Data, Benchmarks and Validation

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

Valentine, Timothy; Rohatgi, Upendra S.

High-fidelity, multi-physics modeling and simulation (M&S) tools are being developed and utilized for a variety of applications in nuclear science and technology and show great promise in their abilities to reproduce observed phenomena for many applications. Even with the increasing fidelity and sophistication of coupled multi-physics M&S tools, the underpinning models and data still need to be validated against experiments that may require a more complex array of validation data because of the great breadth of the time, energy and spatial domains of the physical phenomena that are being simulated. The Expert Group on Multi-Physics Experimental Data, Benchmarks and Validationmore » (MPEBV) of the Nuclear Energy Agency (NEA) of the Organization for Economic Cooperation and Development (OECD) was formed to address the challenges with the validation of such tools. The work of the MPEBV expert group is shared among three task forces to fulfill its mandate and specific exercises are being developed to demonstrate validation principles for common industrial challenges. This paper describes the overall mission of the group, the specific objectives of the task forces, the linkages among the task forces, and the development of a validation exercise that focuses on a specific reactor challenge problem.« less

Direct Interaction between Scaffolding Proteins RACK1 and 14-3-3ζ Regulates Brain-derived Neurotrophic Factor (BDNF) Transcription*

PubMed Central

Neasta, Jérémie; Kiely, Patrick A.; He, Dao-Yao; Adams, David R.; O'Connor, Rosemary; Ron, Dorit

2012-01-01

RACK1 is a scaffolding protein that spatially and temporally regulates numerous signaling cascades. We previously found that activation of the cAMP signaling pathway induces the translocation of RACK1 to the nucleus. We further showed that nuclear RACK1 is required to promote the transcription of the brain-derived neurotrophic factor (BDNF). Here, we set out to elucidate the mechanism underlying cAMP-dependent RACK1 nuclear translocation and BDNF transcription. We identified the scaffolding protein 14-3-3ζ as a direct binding partner of RACK1. Moreover, we found that 14-3-3ζ was necessary for the cAMP-dependent translocation of RACK1 to the nucleus. We further observed that the disruption of RACK1/14-3-3ζ interaction with a peptide derived from the RACK1/14-3-3ζ binding site or shRNA-mediated 14-3-3ζ knockdown inhibited cAMP induction of BDNF transcription. Together, these data reveal that the function of nuclear RACK1 is mediated through its interaction with 14-3-3ζ. As RACK1 and 14-3-3ζ are two multifunctional scaffolding proteins that coordinate a wide variety of signaling events, their interaction is likely to regulate other essential cellular functions. PMID:22069327

Optimization and parallelization of the thermal–hydraulic subchannel code CTF for high-fidelity multi-physics applications

DOE PAGES

Salko, Robert K.; Schmidt, Rodney C.; Avramova, Maria N.

2014-11-23

This study describes major improvements to the computational infrastructure of the CTF subchannel code so that full-core, pincell-resolved (i.e., one computational subchannel per real bundle flow channel) simulations can now be performed in much shorter run-times, either in stand-alone mode or as part of coupled-code multi-physics calculations. These improvements support the goals of the Department Of Energy Consortium for Advanced Simulation of Light Water Reactors (CASL) Energy Innovation Hub to develop high fidelity multi-physics simulation tools for nuclear energy design and analysis.

Preparation and evaluation of effect on Escherichia coli and Staphylococcus aureus of radiolabeled ampicillin-loaded graphene oxide nanoflakes.

PubMed

Yurt, Fatma; Ersöz, Onur Alp; Harputlu, Ersan; Ocakoglu, Kasim

2018-06-01

Ampicillin is a one of effective antibiotics against Gram-positive and Gram-negative bacteria. This study aimed to label ampicillin-loaded graphene oxide nanoflake (AMP-GO) with 99m Tc and evaluate of its in vitro binding to Staphylococcus aureus and Escherichia coli. Firstly, ampicillin was loaded into graphene oxide nanoflake prepared. AMP-GO was characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) techniques, and the amount of loaded ampicillin onto GO was determined by UV-Vis absorption spectroscopy. AMP and AMP-GO were labeled with 99m Tc using stannous chloride reducing agent. Labeling efficiency of 99m Tc-AMP-GO was found to be 97.66 ± 2.06%. 99m Tc-AMP-GO has higher binding efficiencies to both S. aureus and E. coli than 99m Tc-AMP. 99m Tc-AMP-GO could be promising candidate as agent infection nuclear imaging. Furthermore, in vivo studies of 99m Tc-AMP-GO with infected rats are planned to be performed. © 2018 John Wiley & Sons A/S.

Development of high temperature, high radiation resistant silicon semiconductors

NASA Technical Reports Server (NTRS)

Whorl, C. A.; Evans, A. W.

1972-01-01

The development of a hardened silicon power transistor for operation in severe nuclear radiation environments at high temperature was studied. Device hardness and diffusion techniques are discussed along with the geometries of hardened power transistor chips. Engineering drawings of 100 amp and 5 amp silicon devices are included.

Identification and functional characterization of an uncharacterized antimicrobial peptide from a ciliate Paramecium caudatum.

PubMed

Cui, Pengfei; Dong, Yuan; Li, Zhijian; Zhang, Yubo; Zhang, Shicui

2016-07-01

The global ever-growing concerns about multi-drug resistant (MDR) microbes leads to urgent demands for exploration of new antibiotics including antimicrobial peptides (AMPs). Here we demonstrated that a cDNA from Ciliata Paramecium caudatum, designated Pcamp1, coded for a protein with features characteristic of AMPs, which is not homologous to any AMPs currently known. Both the C-terminal 91 amino acid residues of PcAMP1, cPcAMP1, expressed in Escherichia coli and the C-terminal 26 amino acid residues (predicted mature AMP), cPcAMP1/26, synthesized, underwent a coil-to-helix transition in the presence of TFE, SDS or DPC. Functional assays revealed that cPcAMP1 and cPcAMP1/26 were both able to kill Aeromonas hydrophila and Staphylococcus aureus. ELISA showed that cPcAMP1 and cPcAMP1/26 were able to bind to microbe-associated molecular pattern molecules LPS and LTA, which was further corroborated by the observations that cPcAMP1 could deposit onto the bacterial membranes. Importantly, both cPcAMP1 and cPcAMP1/26 were able to induce bacterial membrane permeabilization and depolarization, and to increase intracellular ROS levels. Additionally, cPcAMP1 and cPcAMP1/26 were not cytotoxic to mammalian cells. Taken together, our results show that PcAMP1 is a potential AMP with a membrane selectivity towards bacterial cells, which renders it a promising template for the design of novel peptide antibiotics against MDR microbes. It also shows that use of signal conserved sequence of AMPs can be an effective tool to identify potential AMPs across different animal classes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Faecal colonization of E. coli and Klebsiella spp. producing extended-spectrum beta-lactamases and plasmid-mediated AmpC in Mozambican university students.

PubMed

Chirindze, L M; Zimba, T F; Sekyere, J O; Govinden, U; Chenia, H Y; Sundsfjord, A; Essack, S Y; Simonsen, G S

2018-05-30

In recent years, the world has seen a surge in Enterobacteriaceae resistant to broad-spectrum beta-lactam antibiotics due to the production of extended-spectrum beta-lactamases (ESBLs) or plasmid-mediated AmpC (pAmpC) enzymes. Data on the epidemiology of cephalosporin-resistant Enterobacteriaceae in Sub-Saharan Africa are still limited. Two hundred seventy-five non-repetitive stool samples were collected from Mozambican university students of both sexes. Samples were cultured on MacConkey agar with and without ceftriaxone (1 mg/L) for selection of third-generation cephalosporin-resistant isolates, which were subjected to antimicrobial susceptibility testing by disc diffusion, characterization of resistance genes by PCR and ERIC-PCR analysis for strain clonality. Among the 275 students, 55 (20%) carried a total of 56 E. coli (n = 35) and Klebsiella spp. (n = 21) isolates resistant to ceftriaxone and phenotypically positive for ESBL- and/or pAmpC-production. Forty-three percent of the isolates (24/56) contained only ESBL genes, 11% (6/56) only pAmpC genes, and 36% (20/56) both ESBL and pAmpC genes. The remaining six isolates were negative for the CTX-M/pAmpC genes included in the test panel. E. coli and Klebsiella spp. combined demonstrated 70% resistance to tetracycline and co-trimoxazole, 63% to ceftazidime and 34% to ciprofloxacin. In total, 89% of ESBL/pAmpC-positive isolates were defined as multi-resistant by being resistant to three or more antibiotic classes. ERIC-PCR fingerprinting demonstrated low similarity among isolates. None of the participants reported recent hospitalization and just 12.5% had taken antibiotics 3 months prior to the study. This study demonstrated 20% colonization with multi-resistant E. coli and Klebsiella spp. among Mozambican students with a diversity of ESBL and pAmpC genes. Colonization was not related to prior hospitalization or antimicrobial consumption.

Prevalence of multi drug resistant Acinetobacter baumannii in the clinical samples from Tertiary Care Hospital in Islamabad, Pakistan

PubMed Central

Begum, Shahzeera; Hasan, Fariha; Hussain, Shagufta; Ali Shah, Aamer

2013-01-01

Background & Objectives: Acinetobacter baumannii can cause a wide range of infections, including bacteremia, pneumonia, urinary tract infection, peritonitis, etc. This organism is becoming resistant to a large group of antibiotics, especially β-lactam antibiotics. The reason for multi-drug resistance may be the production of extended- spectrum β-lactamses (ESBLs), carbapenemases/metallo β-lactamases or AmpC β-lactamases. The aim of the present study was to determine the prevalence of multi-drug resistant Acinetobacter baumannii isolated from the patients in Surgical Intensive Care Units (SICUs) of Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan. Methods: A total of 91 A. baumanni isolates were collected from PIMS during the period from February 2011 to December 2011. The antibiotic susceptibility testing was performed by standard disc diffusion method as recommended by CLSI. Combination disc method, Modified Hodge test, EDTA disc synergy test and AmpC disc test were performed for detection of ESBLs, carbapenemases, metallo β-lactamases, and AmpC β-lactamases, respectively. Results: The prevalence of MDRs was reported 100% among A. baumannii. The antibiotic susceptibility profile showed that minocycline and tigecycline were the most effective drugs against A. baumannii. Almost all of A. baumannii isolates were carbapenemase and metallo β-lactamase producers. AmpC prevalence was observed in 41.76%, while none of the isolates was ESBL producer. Antibiogram and minimal inhibitory concentrations (MICs) indicated tetracycline is relatively effective against A. baumanii. Conclusions: Increased frequency of multi-drug resistance supports the need for continuous surveillance to determine prevalence and evolution of these enzymes in Pakistan. PMID:24353731

In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents.

PubMed

Czyzewski, Ann M; Jenssen, Håvard; Fjell, Christopher D; Waldbrook, Matt; Chongsiriwatana, Nathaniel P; Yuen, Eddie; Hancock, Robert E W; Barron, Annelise E

2016-01-01

Bacterial resistance to conventional antibiotics is a global threat that has spurred the development of antimicrobial peptides (AMPs) and their mimetics as novel anti-infective agents. While the bioavailability of AMPs is often reduced due to protease activity, the non-natural structure of AMP mimetics renders them robust to proteolytic degradation, thus offering a distinct advantage for their clinical application. We explore the therapeutic potential of N-substituted glycines, or peptoids, as AMP mimics using a multi-faceted approach that includes in silico, in vitro, and in vivo techniques. We report a new QSAR model that we developed based on 27 diverse peptoid sequences, which accurately correlates antimicrobial peptoid structure with antimicrobial activity. We have identified a number of peptoids that have potent, broad-spectrum in vitro activity against multi-drug resistant bacterial strains. Lastly, using a murine model of invasive S. aureus infection, we demonstrate that one of the best candidate peptoids at 4 mg/kg significantly reduces with a two-log order the bacterial counts compared with saline-treated controls. Taken together, our results demonstrate the promising therapeutic potential of peptoids as antimicrobial agents.

Progress Towards a Rad-Hydro Code for Modern Computing Architectures LA-UR-10-02825

NASA Astrophysics Data System (ADS)

Wohlbier, J. G.; Lowrie, R. B.; Bergen, B.; Calef, M.

2010-11-01

We are entering an era of high performance computing where data movement is the overwhelming bottleneck to scalable performance, as opposed to the speed of floating-point operations per processor. All multi-core hardware paradigms, whether heterogeneous or homogeneous, be it the Cell processor, GPGPU, or multi-core x86, share this common trait. In multi-physics applications such as inertial confinement fusion or astrophysics, one may be solving multi-material hydrodynamics with tabular equation of state data lookups, radiation transport, nuclear reactions, and charged particle transport in a single time cycle. The algorithms are intensely data dependent, e.g., EOS, opacity, nuclear data, and multi-core hardware memory restrictions are forcing code developers to rethink code and algorithm design. For the past two years LANL has been funding a small effort referred to as Multi-Physics on Multi-Core to explore ideas for code design as pertaining to inertial confinement fusion and astrophysics applications. The near term goals of this project are to have a multi-material radiation hydrodynamics capability, with tabular equation of state lookups, on cartesian and curvilinear block structured meshes. In the longer term we plan to add fully implicit multi-group radiation diffusion and material heat conduction, and block structured AMR. We will report on our progress to date.

Rare Isotopes Physics in the Multimessenger Era

NASA Astrophysics Data System (ADS)

Schatz, Hendrik

2018-06-01

While these isotopes only exist for fractions of seconds, their properties shape the resulting cosmic distribution of elements and the astronomical observables including spectra, neutrinos, and gravitational waves. The long standing challenge in nuclear astrophysics of the production of the relevant isotopes in the laboratory is now overcome with a new generation of rare isotope accelerator facilities now coming online. One example is the FRIB facility under construction at Michigan State University for the US Department of Energy, Office of Science, Office of Nuclear Physics. These new capabilities in nuclear physics coincide with advances in astronomy directly related to the cosmic sites where these isotopes are created, in particular in time domain and gravitational wave astronomy. I will discuss the importance of rare isotope physics in interpreting multi-messenger observations and how advances in nuclear physics and astronomy when combined promise to lead us towards a comprehensive theory of the origin of the elements.

77 FR 6143 - Agency Information Collection Activities: Submission for the Office of Management and Budget (OMB...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-07

... Radiation Safety Officer (RSO), authorized medical physicist (AMP), authorized nuclear pharmacist (ANP), or...''; (3) NRC Form 313A (ANP), ``Authorized Nuclear Pharmacist Training and Experience and Preceptor...

cAMP-dependent protein kinase phosphorylates and activates nuclear Ca2+-ATPase

PubMed Central

Rogue, Patrick J.; Humbert, Jean-Paul; Meyer, Alphonse; Freyermuth, Solange; Krady, Marie-Marthe; Malviya, Anant N.

1998-01-01

A Ca2+-pump ATPase, similar to that in the endoplasmic reticulum, has been located on the outer membrane of rat liver nuclei. The effect of cAMP-dependent protein kinase (PKA) on nuclear Ca2+-ATPase (NCA) was studied by using purified rat liver nuclei. Treatment of isolated nuclei with the catalytic unit of PKA resulted in the phosphorylation of a 105-kDa band that was recognized by antibodies specific for sarcoplasmic reticulum Ca2+-ATPase type 2b. Partial purification and immunoblotting confirmed that the 105-kDa protein band phosphorylated by PKA is NCA. The stoichiometry of phosphorylation was 0.76 mol of phosphate incorporated/mol of partially purified enzyme. Measurement of ATP-dependent 45Ca2+ uptake into purified nuclei showed that PKA phosphorylation enhanced the Ca2+-pumping activity of NCA. We show that PKA phosphorylation of Ca2+-ATPase enhances the transport of 10-kDa fluorescent-labeled dextrans across the nuclear envelope. The findings reported in this paper are consistent with the notion that the crosstalk between the cAMP/PKA- and Ca2+-dependent signaling pathways identified at the cytoplasmic level extends to the nucleus. Furthermore, these data support a function for crosstalk in the regulation of calcium-dependent transport across the nuclear envelope. PMID:9689054

Atmospheric, Magnetospheric and Plasmas in Space (AMPS) spacelab payload definition study. Volume 3: Interface control documents. Part 1: AMPS payload to shuttle ICD

NASA Technical Reports Server (NTRS)

1976-01-01

Physical, functional, and operational interfaces between the space shuttle orbiter and the AMPS payload are described for the ground handling and test phases, prelaunch, launch and ascent, operational, stowage, and reentry and landing activities.

A physiological role of AMP-activated protein kinase in phenobarbital-mediated constitutive androstane receptor activation and CYP2B induction

PubMed Central

Shindo, Sawako; Numazawa, Satoshi; Yoshida, Takemi

2006-01-01

CAR (constitutive androstane receptor) is a nuclear receptor that regulates the transcription of target genes, including CYP (cytochrome P450) 2B and 3A. The transactivation by CAR is regulated by its subcellular localization; however, the mechanism that governs nuclear translocation has yet to be clarified. It has been reported recently that AMPK (AMP-activated protein kinase) is involved in phenobarbital-mediated CYP2B induction in a particular culture system. We therefore investigated in vivo whether AMPK is involved in the activation of CAR-dependent gene expression. Immunoblot analysis using an antibody which recognizes Thr-172-phosphorylated AMPKα1/2 revealed phenobarbital-induced AMPK activation in rat and mouse livers as well. Phenobarbital, however, failed to increase the liver phospho-AMPK level of tumour-bearing rats in which CAR nuclear translocation had been impaired. In in vivo reporter gene assays employing PBREM (phenobarbital-responsive enhancer module) from CYP2B1, an AMPK inhibitor 8-bromo-AMP abolished phenobarbital-induced transactivation. In addition, Cyp2b10 gene expression was attenuated by 8-bromo-AMP. Forced expression of a dominant-negative mutant and the wild-type of AMPKα2 in the mouse liver suppressed and further enhanced phenobarbital-induced PBREM-reporter activity respectively. Moreover, the AMPK activator AICAR (5-amino-4-imidazolecarboxamide riboside) induced PBREM transactivation and an accumulation of CAR in the nuclear fraction of the mouse liver. However, AICAR and metformin, another AMPK activator, failed to induce hepatic CYP2B in mice and rats. These observations suggest that AMPK is at least partly involved in phenobarbital-originated signalling, but the kinase activation by itself is not sufficient for CYP2B induction in vivo. PMID:17032173

Scalable Methods for Uncertainty Quantification, Data Assimilation and Target Accuracy Assessment for Multi-Physics Advanced Simulation of Light Water Reactors

NASA Astrophysics Data System (ADS)

Khuwaileh, Bassam

High fidelity simulation of nuclear reactors entails large scale applications characterized with high dimensionality and tremendous complexity where various physics models are integrated in the form of coupled models (e.g. neutronic with thermal-hydraulic feedback). Each of the coupled modules represents a high fidelity formulation of the first principles governing the physics of interest. Therefore, new developments in high fidelity multi-physics simulation and the corresponding sensitivity/uncertainty quantification analysis are paramount to the development and competitiveness of reactors achieved through enhanced understanding of the design and safety margins. Accordingly, this dissertation introduces efficient and scalable algorithms for performing efficient Uncertainty Quantification (UQ), Data Assimilation (DA) and Target Accuracy Assessment (TAA) for large scale, multi-physics reactor design and safety problems. This dissertation builds upon previous efforts for adaptive core simulation and reduced order modeling algorithms and extends these efforts towards coupled multi-physics models with feedback. The core idea is to recast the reactor physics analysis in terms of reduced order models. This can be achieved via identifying the important/influential degrees of freedom (DoF) via the subspace analysis, such that the required analysis can be recast by considering the important DoF only. In this dissertation, efficient algorithms for lower dimensional subspace construction have been developed for single physics and multi-physics applications with feedback. Then the reduced subspace is used to solve realistic, large scale forward (UQ) and inverse problems (DA and TAA). Once the elite set of DoF is determined, the uncertainty/sensitivity/target accuracy assessment and data assimilation analysis can be performed accurately and efficiently for large scale, high dimensional multi-physics nuclear engineering applications. Hence, in this work a Karhunen-Loeve (KL) based algorithm previously developed to quantify the uncertainty for single physics models is extended for large scale multi-physics coupled problems with feedback effect. Moreover, a non-linear surrogate based UQ approach is developed, used and compared to performance of the KL approach and brute force Monte Carlo (MC) approach. On the other hand, an efficient Data Assimilation (DA) algorithm is developed to assess information about model's parameters: nuclear data cross-sections and thermal-hydraulics parameters. Two improvements are introduced in order to perform DA on the high dimensional problems. First, a goal-oriented surrogate model can be used to replace the original models in the depletion sequence (MPACT -- COBRA-TF - ORIGEN). Second, approximating the complex and high dimensional solution space with a lower dimensional subspace makes the sampling process necessary for DA possible for high dimensional problems. Moreover, safety analysis and design optimization depend on the accurate prediction of various reactor attributes. Predictions can be enhanced by reducing the uncertainty associated with the attributes of interest. Accordingly, an inverse problem can be defined and solved to assess the contributions from sources of uncertainty; and experimental effort can be subsequently directed to further improve the uncertainty associated with these sources. In this dissertation a subspace-based gradient-free and nonlinear algorithm for inverse uncertainty quantification namely the Target Accuracy Assessment (TAA) has been developed and tested. The ideas proposed in this dissertation were first validated using lattice physics applications simulated using SCALE6.1 package (Pressurized Water Reactor (PWR) and Boiling Water Reactor (BWR) lattice models). Ultimately, the algorithms proposed her were applied to perform UQ and DA for assembly level (CASL progression problem number 6) and core wide problems representing Watts Bar Nuclear 1 (WBN1) for cycle 1 of depletion (CASL Progression Problem Number 9) modeled via simulated using VERA-CS which consists of several multi-physics coupled models. The analysis and algorithms developed in this dissertation were encoded and implemented in a newly developed tool kit algorithms for Reduced Order Modeling based Uncertainty/Sensitivity Estimator (ROMUSE).

Distinct profiling of antimicrobial peptide families

PubMed Central

Khamis, Abdullah M.; Essack, Magbubah; Gao, Xin; Bajic, Vladimir B.

2015-01-01

Motivation: The increased prevalence of multi-drug resistant (MDR) pathogens heightens the need to design new antimicrobial agents. Antimicrobial peptides (AMPs) exhibit broad-spectrum potent activity against MDR pathogens and kills rapidly, thus giving rise to AMPs being recognized as a potential substitute for conventional antibiotics. Designing new AMPs using current in-silico approaches is, however, challenging due to the absence of suitable models, large number of design parameters, testing cycles, production time and cost. To date, AMPs have merely been categorized into families according to their primary sequences, structures and functions. The ability to computationally determine the properties that discriminate AMP families from each other could help in exploring the key characteristics of these families and facilitate the in-silico design of synthetic AMPs. Results: Here we studied 14 AMP families and sub-families. We selected a specific description of AMP amino acid sequence and identified compositional and physicochemical properties of amino acids that accurately distinguish each AMP family from all other AMPs with an average sensitivity, specificity and precision of 92.88%, 99.86% and 95.96%, respectively. Many of our identified discriminative properties have been shown to be compositional or functional characteristics of the corresponding AMP family in literature. We suggest that these properties could serve as guides for in-silico methods in design of novel synthetic AMPs. The methodology we developed is generic and has a potential to be applied for characterization of any protein family. Contact: vladimir.bajic@kaust.edu.sa Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25388148

Atmosphere, Magnetosphere and Plasmas in Space (AMPS). Spacelab payload definition study. Volume 3, book 2: AMPS equipment to Spacelab ICD

NASA Technical Reports Server (NTRS)

1976-01-01

The interfaces between AMPS Payload No.(TBD) and Spacelab are described. The interfaces specified cover the AMPS physical, electrical, and thermal interfaces that are established to prescribe the standard Spacelab configuration required to perform the mission. If the configuration definition changes due to change of Spacelab equipment model, or serial numbers, then reidentification of the Labcraft payload may be required.

In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents

PubMed Central

Fjell, Christopher D.; Waldbrook, Matt; Chongsiriwatana, Nathaniel P.; Yuen, Eddie; Hancock, Robert E. W.; Barron, Annelise E.

2016-01-01

Bacterial resistance to conventional antibiotics is a global threat that has spurred the development of antimicrobial peptides (AMPs) and their mimetics as novel anti-infective agents. While the bioavailability of AMPs is often reduced due to protease activity, the non-natural structure of AMP mimetics renders them robust to proteolytic degradation, thus offering a distinct advantage for their clinical application. We explore the therapeutic potential of N-substituted glycines, or peptoids, as AMP mimics using a multi-faceted approach that includes in silico, in vitro, and in vivo techniques. We report a new QSAR model that we developed based on 27 diverse peptoid sequences, which accurately correlates antimicrobial peptoid structure with antimicrobial activity. We have identified a number of peptoids that have potent, broad-spectrum in vitro activity against multi-drug resistant bacterial strains. Lastly, using a murine model of invasive S. aureus infection, we demonstrate that one of the best candidate peptoids at 4 mg/kg significantly reduces with a two-log order the bacterial counts compared with saline-treated controls. Taken together, our results demonstrate the promising therapeutic potential of peptoids as antimicrobial agents. PMID:26849681

Mechanisms of protein kinase C signaling in the modulation of 3',5'-cyclic adenosine monophosphate-mediated steroidogenesis in mouse gonadal cells.

PubMed

Manna, Pulak R; Huhtaniemi, Ilpo T; Stocco, Douglas M

2009-07-01

The protein kinase C (PKC) signaling pathway plays integral roles in the expression of the steroidogenic acute regulatory (StAR) protein that regulates steroid biosynthesis in steroidogenic cells. PKC can modulate the activity of cAMP/protein kinase A signaling involved in steroidogenesis; however, its mechanism remains obscure. In the present study, we demonstrate that activation of the PKC pathway, by phorbol 12-myristate 13-acetate (PMA), was capable of potentiating dibutyryl cAMP [(Bu)(2)cAMP]-stimulated StAR expression, StAR phosphorylation, and progesterone synthesis in both mouse Leydig (MA-10) and granulosa (KK-1) tumor cells. The steroidogenic potential of PMA and (Bu)(2)cAMP was linked with phosphorylation of ERK 1/2; however, inhibition of the latter demonstrated varying effects on steroidogenesis. Transcriptional activation of the StAR gene by PMA and (Bu)(2)cAMP was influenced by several factors, its up-regulation being dependent on phosphorylation of the cAMP response element binding protein (CREB). An oligonucleotide probe containing a CREB/activating transcription factor binding region in the StAR promoter was found to bind nuclear proteins in PMA and (Bu)(2)cAMP-treated MA-10 and KK-1 cells. Chromatin immunoprecipitation studies revealed that the induction of phosphorylated CREB was tightly correlated with in vivo protein-DNA interactions and recruitment of CREB binding protein to the StAR promoter. Ectopic expression of CREB binding protein enhanced CREB-mediated transcription of the StAR gene, an event that was markedly repressed by the adenovirus E1A oncoprotein. Further studies demonstrated that the activation of StAR expression and steroid synthesis by PMA and (Bu)(2)cAMP was associated with expression of the nuclear receptor Nur77, indicating its essential role in hormone-regulated steroidogenesis. Collectively, these findings provide insight into the mechanisms by which PKC modulates cAMP/protein kinase A responsiveness involved in regulating the steroidogenic response in mouse gonadal cells.

Phosphodiesterase inhibitors suppress Lactobacillus casei cell-wall-induced NF-κB and MAPK activations and cell proliferation through protein kinase A--or exchange protein activated by cAMP-dependent signal pathway.

PubMed

Saito, Takekatsu; Sugimoto, Naotoshi; Ohta, Kunio; Shimizu, Tohru; Ohtani, Kaori; Nakayama, Yuko; Nakamura, Taichi; Hitomi, Yashiaki; Nakamura, Hiroyuki; Koizumi, Shoichi; Yachie, Akihiro

2012-01-01

Specific strains of Lactobacillus have been found to be beneficial in treating some types of diarrhea and vaginosis. However, a high mortality rate results from underlying immunosuppressive conditions in patients with Lactobacillus casei bacteremia. Cyclic AMP (cAMP) is a small second messenger molecule that mediates signal transduction. The onset and progression of inflammatory responses are sensitive to changes in steady-state cAMP levels. L. casei cell wall extract (LCWE) develops arteritis in mice through Toll-like receptor-2 signaling. The purpose of this study was to investigate whether intracellular cAMP affects LCWE-induced pathological signaling. LCWE was shown to induce phosphorylation of the nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways and cell proliferation in mice fibroblast cells. Theophylline and phosphodiesterase inhibitor increased intracellular cAMP and inhibited LCWE-induced cell proliferation as well as phosphorylation of NF-κB and MAPK. Protein kinase A inhibitor H89 prevented cAMP-induced MAPK inhibition, but not cAMP-induced NF-κB inhibition. An exchange protein activated by cAMP (Epac) agonist inhibited NF-κB activation but not MAPK activation. These results indicate that an increase in intracellular cAMP prevents LCWE induction of pathological signaling pathways dependent on PKA and Epac signaling.

The 2′,3′-cAMP-adenosine pathway

PubMed Central

2011-01-01

Our recent studies employing HPLC-tandem mass spectrometry to analyze venous perfusate from isolated, perfused kidneys demonstrate that intact kidneys produce and release into the extracellular compartment 2′,3′-cAMP, a positional isomer of the second messenger 3′,5′-cAMP. To our knowledge, this represents the first detection of 2′,3′-cAMP in any cell/tissue/organ/organism. Nuclear magnetic resonance experiments with isolated RNases and experiments in isolated, perfused kidneys suggest that 2′,3′-cAMP likely arises from RNase-mediated transphosphorylation of mRNA. Both in vitro and in vivo kidney experiments demonstrate that extracellular 2′,3′-cAMP is efficiently metabolized to 2′-AMP and 3′-AMP, both of which can be further metabolized to adenosine. This sequence of reactions is called the 2′,3′-cAMP-adenosine pathway (2′,3′-cAMP → 2′-AMP/3′-AMP → adenosine). Experiments in rat and mouse kidneys show that metabolic poisons increase extracellular levels of 2′,3′-cAMP, 2′-AMP, 3′-AMP, and adenosine; however, little is known regarding the pharmacology of 2′,3′-cAMP, 2′-AMP, and 3′-AMP. What is known is that 2′,3′-cAMP facilitates activation of mitochondrial permeability transition pores, a process that can lead to apoptosis and necrosis, and inhibits proliferation of vascular smooth muscle cells and glomerular mesangial cells. In summary, there is mounting evidence that at least some types of cellular injury, by triggering mRNA degradation, engage the 2′,3′-cAMP-adenosine pathway, and therefore this pathway should be added to the list of biochemical pathways that produce adenosine. Although speculative, it is possible that the 2′,3′-cAMP-adenosine pathway may protect against some forms of acute organ injury, for example acute kidney injury, by both removing an intracellular toxin (2′,3′-cAMP) and increasing an extracellular renoprotectant (adenosine). PMID:21937608

cAMP inhibits inducible nitric oxide synthase expression and NF-kappaB-binding activity in cultured rat hepatocytes.

PubMed

Harbrecht, B G; Taylor, B S; Xu, Z; Ramalakshmi, S; Ganster, R W; Geller, D A

2001-08-01

The inducible nitric oxide synthase (iNOS) is strongly expressed following inflammatory stimuli. Adenosine 3',5'-cyclic monophosphate (cAMP) increases iNOS expression and activity in a number of cell types but decreases cytokine-stimulated iNOS expression in hepatocytes. The mechanisms for this effect are unknown. Rat hepatocytes were stimulated with cytokines to induce iNOS and cultured with cAMP agonists dibutyryl-cAMP (dbcAMP), 8-bromo-cAMP, and forskolin (FSK). Nitric oxide synthesis was assessed by supernatant nitrite levels and iNOS expression was measured by Northern and Western blot analyses. Nuclear factor kappaB binding was assessed by electromobility shift assay. Cyclic AMP dose dependently decreased NO synthesis in response to a combination of proinflammatory cytokines or interleukin-1beta (IL-1beta) alone. The adenylate cyclase inhibitor SQ 22,536 increased cytokine- or IL-1beta-stimulated NO synthesis. dbcAMP decreased iNOS mRNA expression and iNOS protein expression. Both dbcAMP and glucagon decreased iNOS promoter activity in rat hepatocytes transfected with the murine iNOS promoter and decreased DNA binding of the transcription factor NF-kappaB. These data suggest that cAMP is important in hepatocyte iNOS expression and agents that alter cAMP levels may profoundly alter the response of hepatocytes to inflammatory stimuli through effects onthe iNOS promoter region and NF-kappaB. Copyright 2001 Academic Press.

Atmospheric, Magnetospheric and Plasmas in Space (AMPS) spacelab payload definition study. Volume 3: Interface control documents. Part 3: AMPS payload to instruments ICD

NASA Technical Reports Server (NTRS)

1976-01-01

General physical, functional, and operational interface control requirements for instruments on the first AMPS payload are presented. Interface specifications are included to satisfy ground handling, prelaunch, launch, stowage, operation, and landing activities. Applicable supporting documentation to implement the information is also given.

Studies related to primitive chemistry. A proton and nitrogen-14 nuclear magnetic resonance amino acid and nucleic acid constituents and a and their possible relation to prebiotic

NASA Technical Reports Server (NTRS)

Manatt, S. L.; Cohen, E. A.; Shiller, A. M.; Chan, S. I.

1973-01-01

Preliminary proton nuclear magnetic resonance (NMR) studies were made to determine the applicability of this technique for the study of interactions between monomeric and polymeric amino acids with monomeric nucleic acid bases and nucleotides. Proton NMR results for aqueous solutions (D2O) demonstrated interactions between the bases cytosine and adenine and acidic and aromatic amino acids. Solutions of 5'-AMP admixed with amino acids exhibited more complex behavior but stacking between aromatic rings and destacking at high amino acids concentration was evident. The multisite nature of 5'-AMP was pointed out. Chemical shift changes for adenine and 5'-AMP with three water soluble polypeptides demonstrated that significant interactions exist. It was found that the linewidth-pH profile of each amino acid is unique. It is concluded that NMR techniques can give significant and quantitative data on the association of amino acid and nucleic acid constituents.

Cardiac Hypertrophy Is Inhibited by a Local Pool of cAMP Regulated by Phosphodiesterase 2.

PubMed

Zoccarato, Anna; Surdo, Nicoletta C; Aronsen, Jan M; Fields, Laura A; Mancuso, Luisa; Dodoni, Giuliano; Stangherlin, Alessandra; Livie, Craig; Jiang, He; Sin, Yuan Yan; Gesellchen, Frank; Terrin, Anna; Baillie, George S; Nicklin, Stuart A; Graham, Delyth; Szabo-Fresnais, Nicolas; Krall, Judith; Vandeput, Fabrice; Movsesian, Matthew; Furlan, Leonardo; Corsetti, Veronica; Hamilton, Graham; Lefkimmiatis, Konstantinos; Sjaastad, Ivar; Zaccolo, Manuela

2015-09-25

Chronic elevation of 3'-5'-cyclic adenosine monophosphate (cAMP) levels has been associated with cardiac remodeling and cardiac hypertrophy. However, enhancement of particular aspects of cAMP/protein kinase A signaling seems to be beneficial for the failing heart. cAMP is a pleiotropic second messenger with the ability to generate multiple functional outcomes in response to different extracellular stimuli with strict fidelity, a feature that relies on the spatial segregation of the cAMP pathway components in signaling microdomains. How individual cAMP microdomains affect cardiac pathophysiology remains largely to be established. The cAMP-degrading enzymes phosphodiesterases (PDEs) play a key role in shaping local changes in cAMP. Here we investigated the effect of specific inhibition of selected PDEs on cardiac myocyte hypertrophic growth. Using pharmacological and genetic manipulation of PDE activity, we found that the rise in cAMP resulting from inhibition of PDE3 and PDE4 induces hypertrophy, whereas increasing cAMP levels via PDE2 inhibition is antihypertrophic. By real-time imaging of cAMP levels in intact myocytes and selective displacement of protein kinase A isoforms, we demonstrate that the antihypertrophic effect of PDE2 inhibition involves the generation of a local pool of cAMP and activation of a protein kinase A type II subset, leading to phosphorylation of the nuclear factor of activated T cells. Different cAMP pools have opposing effects on cardiac myocyte cell size. PDE2 emerges as a novel key regulator of cardiac hypertrophy in vitro and in vivo, and its inhibition may have therapeutic applications. © 2015 American Heart Association, Inc.

Between-monitor differences in step counts are related to body size: implications for objective physical activity measurement.

PubMed

Pomeroy, Jeremy; Brage, Søren; Curtis, Jeffrey M; Swan, Pamela D; Knowler, William C; Franks, Paul W

2011-04-27

The quantification of the relationships between walking and health requires that walking is measured accurately. We correlated different measures of step accumulation to body size, overall physical activity level, and glucose regulation. Participants were 25 men and 25 women American Indians without diabetes (Age: 20-34 years) in Phoenix, Arizona, USA. We assessed steps/day during 7 days of free living, simultaneously with three different monitors (Accusplit-AX120, MTI-ActiGraph, and Dynastream-AMP). We assessed total physical activity during free-living with doubly labeled water combined with resting metabolic rate measured by expired gas indirect calorimetry. Glucose tolerance was determined during an oral glucose tolerance test. Based on observed counts in the laboratory, the AMP was the most accurate device, followed by the MTI and the AX120, respectively. The estimated energy cost of 1000 steps per day was lower in the AX120 than the MTI or AMP. The correlation between AX120-assessed steps/day and waist circumference was significantly higher than the correlation between AMP steps and waist circumference. The difference in steps per day between the AX120 and both the AMP and the MTI were significantly related to waist circumference. Between-monitor differences in step counts influence the observed relationship between walking and obesity-related traits.

Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity

PubMed Central

Ozcan, Lale; Wong, Catherine C.L.; Li, Gang; Xu, Tao; Pajvani, Utpal; Park, Sung Kyu Robin; Wronska, Anetta; Chen, Bi-Xing; Marks, Andrew R.; Fukamizu, Akiyoshi; Backs, Johannes; Singer, Harold A.; Yates, John R.; Accili, Domenico; Tabas, Ira

2012-01-01

SUMMARY Hepatic glucose production (HGP) is crucial for glucose homeostasis, but the underlying mechanisms have not been fully elucidated. Here we show that a calcium-sensing enzyme, CaMKII, is activated in a calcium- and IP3R-dependent manner by cAMP and glucagon in primary HCs and by glucagon and fasting in vivo. Genetic deficiency or inhibition of CaMKII blocks nuclear translocation of FoxO1 by affecting its phosphorylation, impairs fasting- and glucagon/cAMP-induced glycogenolysis and gluconeogenesis, and lowers blood glucose levels, while constitutively active CaMKII has the opposite effects. Importantly, the suppressive effect of CaMKII deficiency on glucose metabolism is abrogated by transduction with constitutively nuclear FoxO1, indicating that the effect of CaMKII deficiency requires nuclear exclusion of FoxO1. This same pathway is also involved in excessive HGP in the setting of obesity. These results reveal a calcium-mediated signaling pathway involved in FoxO1 nuclear localization and hepatic glucose homeostasis. PMID:22503562

UCR1C is a novel activator of phosphodiesterase 4 (PDE4) long isoforms and attenuates cardiomyocyte hypertrophy.

PubMed

Wang, Li; Burmeister, Brian T; Johnson, Keven R; Baillie, George S; Karginov, Andrei V; Skidgel, Randal A; O'Bryan, John P; Carnegie, Graeme K

2015-05-01

Hypertrophy increases the risk of heart failure and arrhythmia. Prevention or reversal of the maladaptive hypertrophic phenotype has thus been proposed to treat heart failure. Chronic β-adrenergic receptor (β-AR) stimulation induces cardiomyocyte hypertrophy by elevating 3',5'-cyclic adenosine monophosphate (cAMP) levels and activating downstream effectors such protein kinase A (PKA). Conversely, hydrolysis of cAMP by phosphodiesterases (PDEs) spatiotemporally restricts cAMP signaling. Here, we demonstrate that PDE4, but not PDE3, is critical in regulating cardiomyocyte hypertrophy, and may represent a potential target for preventing maladaptive hypertrophy. We identify a sequence within the upstream conserved region 1 of PDE4D, termed UCR1C, as a novel activator of PDE4 long isoforms. UCR1C activates PDE4 in complex with A-kinase anchoring protein (AKAP)-Lbc resulting in decreased PKA signaling facilitated by AKAP-Lbc. Expression of UCR1C in cardiomyocytes inhibits hypertrophy in response to chronic β-AR stimulation. This effect is partially due to inhibition of nuclear PKA activity, which decreases phosphorylation of the transcription factor cAMP response element-binding protein (CREB). In conclusion, PDE4 activation by UCR1C attenuates cardiomyocyte hypertrophy by specifically inhibiting nuclear PKA activity. Published by Elsevier Inc.

Sandia National Laboratories: Directed-energy tech receives funding to

Science.gov Websites

Accomplishments Energy Stationary Power Earth Science Transportation Energy Energy Research Global Security WMD & Figures Programs Nuclear Weapons About Nuclear Weapons Safety & Security Weapons Science & Cyber & Infrastructure Security Global Security Remote Sensing & Verification Research Research

Regulation of Phosphorylation of a Specific Protein in Toad-Bladder Membrane by Antidiuretic Hormone and Cyclic AMP, and Its Possible Relationship to Membrane Permeability Changes

PubMed Central

DeLorenzo, Robert J.; Walton, Kenneth G.; Curran, Peter F.; Greengard, Paul

1973-01-01

Phosphorylation of a specific protein was decreased in intact toad bladders by exposure to either antidiuretic hormone or monobutyryl cyclic AMP. The decrease in phosphorylation caused by these agents preceded the change in electrical potential difference (an indicator of the rate of sodium ion transport) observed in response to the same compounds. The addition of cyclic AMP to homogenates of toad bladder led to a decrease in phosphorylation of the same, or a similar, protein. In subcellular fractionation studies, the effect of cyclic AMP on the phosphorylation of this protein was observed in those fractions rich in membrane fragments, but not in the nuclear or cell-sap fractions. These and other results are compatible with the possibility that the regulation by vasopressin and cyclic AMP of sodium and/or water transport in toad bladder may be mediated through regulation of the phosphorylation of this specific protein. Images PMID:4351809

Comparison of antifungal efficacies of moxifloxacin, liposomal amphotericin B, and combination treatment in experimental Candida albicans endophthalmitis in rabbits.

PubMed

Deren, Yudum Tiftikcioğlu; Ozdek, Sengül; Kalkanci, Ayşe; Akyürek, Nalan; Hasanreisoğlu, Berati

2010-01-01

The goal of this study was to compare in vitro and in vivo efficacy of moxifloxacin and liposomal amphotericin B (Amp-B) monotherapies and combination treatment against Candida albicans in an exogenous endophthalmitis model in rabbit eyes. Microplate dilution tests and checkerboard analysis were performed to detect in vitro efficacies. Endophthalmitis was induced by intravitreal injection of C. albicans in 40 rabbit eyes with simultaneous intravitreal drug injection according to prophylactic treatment groups. Group 1 (control group) received 0.1 mL of balanced salt solution, group 2 (moxi group) 100 microg moxifloxacin/0.1 mL, group 3 (Amp-B group) 10 microg liposomal Amp-B/0.1 mL, and group 4 (combi group) both 100 microg moxifloxacin/0.1 mL [DOSAGE ERROR CORRECTED] and 10 microg liposomal Amp-B/0.05 mL intravitreally. Clinical examination, quantitative analysis of microorganisms, and histopathologic examination were performed as in vivo studies. The minimum inhibitory concentration of liposomal Amp-B against C. albicans was found to be 1 microg/mL. Moxifloxacin showed no inhibition of in vitro C. albicans growth. The minimum inhibitory concentration values of liposomal Amp-B for C. albicans were reduced two- to eightfold with increasing concentrations of moxifloxacin in vitro. In vivo, there was no C. albicans growth in the combi group (zero of eight eyes), whereas three eyes (37.5%) showed growth in the Amp-B group. Vitreous inflammation, retinal detachment, focal retinal necrosis, and outer nuclear layer loss were found to be lower in the moxi group compared with the control group. Ganglion cell and inner nuclear layer loss was observed in all eyes (100%) in both the moxi and combi groups, whereas only in 25% (two of eight eyes) in the Amp-B group. Moxifloxacin strongly augments the efficacy of liposomal Amp-B against C. albicans in vitro, although it has no in vitro antifungal activity when used alone. It is interesting that we found a synergistic effect for in vitro tests but failed to demonstrate it in vivo. When 100 microg moxifloxacin/0.1 mL is given intravitreally, it has some toxic effects that are limited to the inner retinal layers.

Computing Properties of Hadrons, Nuclei and Nuclear Matter from Quantum Chromodynamics

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

Savage, Martin J.

This project was part of a coordinated software development effort which the nuclear physics lattice QCD community pursues in order to ensure that lattice calculations can make optimal use of present, and forthcoming leadership-class and dedicated hardware, including those of the national laboratories, and prepares for the exploitation of future computational resources in the exascale era. The UW team improved and extended software libraries used in lattice QCD calculations related to multi-nucleon systems, enhanced production running codes related to load balancing multi-nucleon production on large-scale computing platforms, and developed SQLite (addressable database) interfaces to efficiently archive and analyze multi-nucleon datamore » and developed a Mathematica interface for the SQLite databases.« less

Recycling antibiotics into GUMBOS: A new combination strategy to combat multi-drug resistant bacteria

USDA-ARS?s Scientific Manuscript database

The emergence of multi-drug resistant bacteria, coupled with the lack of new antibiotics in development, is fast evolving into a global crisis. New strategies utilizing existing antibacterial agents are urgently needed. We propose one such strategy in which four outmoded ß-lactam antibiotics (amp...

Antimicrobial peptides and induced membrane curvature: geometry, coordination chemistry, and molecular engineering

PubMed Central

Schmidt, Nathan W.; Wong, Gerard C. L.

2013-01-01

Short cationic, amphipathic antimicrobial peptides are multi-functional molecules that have roles in host defense as direct microbicides and modulators of the immune response. While a general mechanism of microbicidal activity involves the selective disruption and permeabilization of cell membranes, the relationships between peptide sequence and membrane activity are still under investigation. Here, we review the diverse functions that AMPs collectively have in host defense, and show that these functions can be multiplexed with a membrane mechanism of activity derived from the generation of negative Gaussian membrane curvature. As AMPs preferentially generate this curvature in model bacterial cell membranes, the selective generation of negative Gaussian curvature provides AMPs with a broad mechanism to target microbial membranes. The amino acid constraints placed on AMPs by the geometric requirement to induce negative Gaussian curvature are consistent with known AMP sequences. This ‘saddle-splay curvature selection rule’ is not strongly restrictive so AMPs have significant compositional freedom to multiplex membrane activity with other useful functions. The observation that certain proteins involved in cellular processes which require negative Gaussian curvature contain domains with similar motifs as AMPs, suggests this rule may be applicable to other curvature-generating proteins. Since our saddle-splay curvature design rule is based upon both a mechanism of activity and the existing motifs of natural AMPs, we believe it will assist the development of synthetic antimicrobials. PMID:24778573

Pathogenic and commensal Escherichia coli from irrigation water show potential in transmission of extended spectrum and AmpC β-lactamases determinants to isolates from lettuce

PubMed Central

Njage, Patrick M K; Buys, Elna M

2015-01-01

There are few studies on the presence of extended-spectrum β-lactamases and AmpC β-lactamases (ESBL/AmpC) in bacteria that contaminate vegetables. The role of the production environment in ESBL/AmpC gene transmission is poorly understood. The occurrence of ESBL/AmpC in Escherichia coli (n = 46) from lettuce and irrigation water and the role of irrigation water in the transmission of resistant E. coli were studied. The presence of ESBL/AmpC, genetic similarity and phylogeny were typed using genotypic and phenotypic techniques. The frequency of β-lactamase gene transfer was studied in vitro. ESBLs/AmpC were detected in 35 isolates (76%). Fourteen isolates (30%) produced both ESBLs/AmpC. Prevalence was highest in E. coli from lettuce (90%). Twenty-two isolates (48%) were multi-resistant with between two and five ESBL/AmpC genes. The major ESBL determinant was the CTX-M type (34 isolates). DHA (33% of isolates) were the dominant AmpC β lactamases. There was a high conjugation efficiency among the isolates, ranging from 3.5 × 10−2 to 1 × 10−2 ± 1.4 × 10−1 transconjugants per recipient. Water isolates showed a significantly higher conjugation frequency than those from lettuce. A high degree of genetic relatedness between E. coli from irrigation water and lettuce indicated possible common ancestry and pathway of transmission. PMID:25488608

Minding the Cyber-Physical Gap: Model-Based Analysis and Mitigation of Systemic Perception-Induced Failure.

PubMed

Mordecai, Yaniv; Dori, Dov

2017-07-17

The cyber-physical gap (CPG) is the difference between the 'real' state of the world and the way the system perceives it. This discrepancy often stems from the limitations of sensing and data collection technologies and capabilities, and is inevitable at some degree in any cyber-physical system (CPS). Ignoring or misrepresenting such limitations during system modeling, specification, design, and analysis can potentially result in systemic misconceptions, disrupted functionality and performance, system failure, severe damage, and potential detrimental impacts on the system and its environment. We propose CPG-Aware Modeling & Engineering (CPGAME), a conceptual model-based approach to capturing, explaining, and mitigating the CPG. CPGAME enhances the systems engineer's ability to cope with CPGs, mitigate them by design, and prevent erroneous decisions and actions. We demonstrate CPGAME by applying it for modeling and analysis of the 1979 Three Miles Island 2 nuclear accident, and show how its meltdown could be mitigated. We use ISO-19450:2015-Object Process Methodology as our conceptual modeling framework.

Adenosine 5'-monophosphate ameliorates D-galactosamine/lipopolysaccharide-induced liver injury through an adenosine receptor-independent mechanism in mice.

PubMed

Zhan, Y; Wang, Z; Yang, P; Wang, T; Xia, L; Zhou, M; Wang, Y; Wang, S; Hua, Z; Zhang, J

2014-01-09

D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced lethality and acute liver failure is dependent on endogenously produced inflammatory cytokines. Adenosine has been proven to be a central role in the regulation of inflammatory response. It is not entirely clear that which adenosine action is actually crucial to limiting inflammatory tissue destruction. Here we showed that GalN/LPS challenge elevated hepatic adenosine and induced lethality in adenosine receptor-deficient mice with equal efficiency as wild-type mice. In GalN/LPS-treated mice, pretreatment with adenosine 5'-monophosphate (5'-AMP) significantly elevated hepatic adenosine level and reduced mortality through decreasing cytokine and chemokine production. In RAW264.7 cells, 5'-AMP treatment inhibited the production of inflammatory cytokines, which is not mediated through adenosine receptors. 5'-AMP failed to attenuate LPS-induced nuclear factor-κB (NF-κB) p65 nuclear translocation, but reduced LPS-induced recruitment of NF-κB p65 to inflammatory gene promoters and decreased LPS-induced enrichment of H3K4 dimethylation at the tumor necrosis factor-α (TNF-α) promoter, which was involved in 5'-AMP-induced elevation of cellular adenosine and a decline of methylation potential. In vitro biochemical analysis revealed that adenosine directly attenuated recruitment of NF-κB to the TNF-α and interleukin-6 promoters. Our findings demonstrate that 5'-AMP-inhibiting inflammatory response is not mediated by adenosine receptors and it may represent a potential protective agent for amelioration of LPS-induced liver injury.

Adenosine 5′-monophosphate ameliorates D-galactosamine/lipopolysaccharide-induced liver injury through an adenosine receptor-independent mechanism in mice

PubMed Central

Zhan, Y; Wang, Z; Yang, P; Wang, T; Xia, L; Zhou, M; Wang, Y; Wang, S; Hua, Z; Zhang, J

2014-01-01

D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced lethality and acute liver failure is dependent on endogenously produced inflammatory cytokines. Adenosine has been proven to be a central role in the regulation of inflammatory response. It is not entirely clear that which adenosine action is actually crucial to limiting inflammatory tissue destruction. Here we showed that GalN/LPS challenge elevated hepatic adenosine and induced lethality in adenosine receptor-deficient mice with equal efficiency as wild-type mice. In GalN/LPS-treated mice, pretreatment with adenosine 5′-monophosphate (5′-AMP) significantly elevated hepatic adenosine level and reduced mortality through decreasing cytokine and chemokine production. In RAW264.7 cells, 5′-AMP treatment inhibited the production of inflammatory cytokines, which is not mediated through adenosine receptors. 5′-AMP failed to attenuate LPS-induced nuclear factor-κB (NF-κB) p65 nuclear translocation, but reduced LPS-induced recruitment of NF-κB p65 to inflammatory gene promoters and decreased LPS-induced enrichment of H3K4 dimethylation at the tumor necrosis factor-α (TNF-α) promoter, which was involved in 5′-AMP-induced elevation of cellular adenosine and a decline of methylation potential. In vitro biochemical analysis revealed that adenosine directly attenuated recruitment of NF-κB to the TNF-α and interleukin-6 promoters. Our findings demonstrate that 5′-AMP-inhibiting inflammatory response is not mediated by adenosine receptors and it may represent a potential protective agent for amelioration of LPS-induced liver injury. PMID:24407238

Immunocytology on microwave-fixed cells reveals rapid and agonist-specific changes in subcellular accumulation patterns for cAMP or cGMP.

PubMed Central

Barsony, J; Marx, S J

1990-01-01

We developed a method for cAMP and cGMP immunocytology based upon fixation by microwave irradiation. Fixation by microwave irradiation prevented three problems found with other fixation methods: nucleotide loss from cells, nucleotide diffusion within cells, and chemical modification of immunologic epitopes. Six agonists (four that stimulate adenylate cyclase and two that stimulate guanylate cyclase) produced cAMP or cGMP accumulation patterns that were agonist-specific, dose-dependent, detectable at physiologic concentrations of hormone, and time-dependent within 15 sec to 30 min. cAMP accumulation after 1 mM forskolin was greatest in the nucleus. Isoproterenol, prostaglandin E2, or calcitonin caused initial accumulation of cAMP along the plasma membrane, but later accumulation was greater in the cytoplasm. With calcitonin the later accumulation of cAMP was selectively perinuclear and along the nuclear membrane. Sodium nitroprusside stimulated cGMP accumulation diffusely throughout the cytoplasm. Atrial natriuretic peptide initiated cGMP accumulation near the plasma membrane, and cGMP accumulation moved from there into the cytoplasm. In conclusion, microwave irradiation preserved cell structure and allowed visualization of expected as well as unsuspected changes in intracellular accumulation patterns of cAMP and cGMP. Images PMID:2153973

Seamount ecology and dynamics: A multidisciplinary data set from repeated surveys at different seamounts in the Northeast Atlantic and Mediterranean (2003 - 2013).

NASA Astrophysics Data System (ADS)

Mohn, C.; Christiansen, B.; Denda, A.; George, K. H.; Kaufmann, M.; Maranhão, M.; Martin, B.; Metzger, T.; Peine, F.; Schuster, A.; Springer, B.; Stefanowitsch, B.; Turnewitsch, R.; Wehrmann, H.

2016-02-01

Seamounts are amongst the most common physiographic open ocean systems, but remoteness and geographic complexity have limited the number of integrated and multidisciplinary seamount surveys in the past. As a consequence, important aspects of seamount ecology and dynamics remain poorly studied. Here we present a multi-parameter data set from individual and repeated seamount surveys conducted at different sites in the Northeast Atlantic and Eastern Mediterranean between 2003 and 2013. The main objective of these surveys was to establish a collection of ecosystem relevant descriptors and to develop a better understanding of seamount ecosystem composition and variability in different dynamical and bio-geographic environments. Measurements were conducted at four seamounts in the Northeast Atlantic (Ampère, Sedlo, Seine, Senghor) and two seamounts in the Eastern Mediterranean (Anaximenes, Eratosthenes). The data set comprises records from a total number of 11 cruises including physical oceanography (temperature, salinity, pressure, currents), biology (phytoplankton, zooplankton, fish, benthos) and biogeochemistry (sedimentary particle dynamics, carbon flux). The resulting multi-disciplinary data collection provides a unique opportunity for comparative studies of seamount ecosystem structure and dynamics between different physical, biological and biogeochemical regimes

Bypass Diode Temperature Tests of a Solar Array Coupon Under Space Thermal Environment Conditions

NASA Technical Reports Server (NTRS)

Wright, Kenneth H., Jr.; Schneider, Todd A.; Vaughn, Jason A.; Hoang, Bao; Wong, Frankie; Wu, Gordon

2016-01-01

Tests were performed on a 56-cell Advanced Triple Junction solar array coupon whose purpose was to determine margin available for bypass diodes integrated with new, large multi-junction solar cells that are manufactured from a 4-inch wafer. The tests were performed under high vacuum with coupon back side thermal conditions of both cold and ambient. The bypass diodes were subjected to a sequence of increasing discrete current steps from 0 Amp to 2.0 Amp in steps of 0.25 Amp. At each current step, a temperature measurement was obtained via remote viewing by an infrared camera. This paper discusses the experimental methodology, experiment results, and the thermal model.

By-Pass Diode Temperature Tests of a Solar Array Coupon Under Space Thermal Environment Conditions

NASA Technical Reports Server (NTRS)

Wright, Kenneth H., Jr.; Schneider, Todd A.; Vaughn, Jason A.; Hoang, Bao; Wong, Frankie

2016-01-01

Tests were performed on a 56-cell Advanced Triple Junction solar array coupon whose purpose was to determine margin available for bypass diodes integrated with new, large multi-junction solar cells that are manufactured from a 4-inch wafer. The tests were performed under high vacuum with cold and ambient coupon back-side. The bypass diodes were subjected to a sequence of increasing discrete current steps from 0 Amp to 2.0 Amp in steps of 0.25 Amp. At each current step, a temperature measurement was obtained via remote viewing by an infrared camera. This paper discusses the experimental methodology, including the calibration of the thermal imaging system, and the results.

[Forskolin inhibits spontaneous contraction of gastric antral smooth muscle in rats].

PubMed

Jiang, Jing-Zhi; Sun, Qian; Xu, Dong-Yuan; Zhang, Mo-Han; Piao, Li-Hua; Cai, Ying-Lan; Jin, Zheng

2013-04-25

The aim of the present study was to investigate the effects of cyclic adenosine monophosphate (cAMP) on rat gastric antral circular smooth muscle function. Forskolin, a direct activator of adenylyl cyclase (AC), was used to observe the influences of cAMP. Multi-channel physiological recorder was used to record spontaneous contraction activity of gastric antral circular muscle from Wistar rats. And ELISA method was used to detect the change of cAMP production in perfusate. The results showed that forskolin concentration-dependently suppressed the amplitude and frequency of the spontaneous contraction of the gastric antral muscle, and lowered the baseline of contraction movement significantly. Forskolin concentration-dependently increased the production of cAMP in the perfusate, which showed a significant negative correlation with the contraction amplitude of gastric antral ring muscle. The inhibitory effect of forskolin on spontaneous contraction activity of rat gastric antral circular muscle could be blocked by cAMP-dependent protein kinase (PKA) inhibitor H-89. These results suggest forskolin increases cAMP production and then activates PKA pathway, resulting in the inhibition of the spontaneous contraction activity of rat gastric antral circular smooth muscle.

The CGTCA sequence motif is essential for biological activity of the vasoactive intestinal peptide gene cAMP-regulated enhancer.

PubMed Central

Fink, J S; Verhave, M; Kasper, S; Tsukada, T; Mandel, G; Goodman, R H

1988-01-01

cAMP-regulated transcription of the human vasoactive intestinal peptide gene is dependent upon a 17-base-pair DNA element located 70 base pairs upstream from the transcriptional initiation site. This element is similar to sequences in other genes known to be regulated by cAMP and to sequences in several viral enhancers. We have demonstrated that the vasoactive intestinal peptide regulatory element is an enhancer that depends upon the integrity of two CGTCA sequence motifs for biological activity. Mutations in either of the CGTCA motifs diminish the ability of the element to respond to cAMP. Enhancers containing the CGTCA motif from the somatostatin and adenovirus genes compete for binding of nuclear proteins from C6 glioma and PC12 cells to the vasoactive intestinal peptide enhancer, suggesting that CGTCA-containing enhancers interact with similar transacting factors. Images PMID:2842787

Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity.

PubMed

Ozcan, Lale; Wong, Catherine C L; Li, Gang; Xu, Tao; Pajvani, Utpal; Park, Sung Kyu Robin; Wronska, Anetta; Chen, Bi-Xing; Marks, Andrew R; Fukamizu, Akiyoshi; Backs, Johannes; Singer, Harold A; Yates, John R; Accili, Domenico; Tabas, Ira

2012-05-02

Hepatic glucose production (HGP) is crucial for glucose homeostasis, but the underlying mechanisms have not been fully elucidated. Here, we show that a calcium-sensing enzyme, CaMKII, is activated in a calcium- and IP3R-dependent manner by cAMP and glucagon in primary hepatocytes and by glucagon and fasting in vivo. Genetic deficiency or inhibition of CaMKII blocks nuclear translocation of FoxO1 by affecting its phosphorylation, impairs fasting- and glucagon/cAMP-induced glycogenolysis and gluconeogenesis, and lowers blood glucose levels, while constitutively active CaMKII has the opposite effects. Importantly, the suppressive effect of CaMKII deficiency on glucose metabolism is abrogated by transduction with constitutively nuclear FoxO1, indicating that the effect of CaMKII deficiency requires nuclear exclusion of FoxO1. This same pathway is also involved in excessive HGP in the setting of obesity. These results reveal a calcium-mediated signaling pathway involved in FoxO1 nuclear localization and hepatic glucose homeostasis. Copyright © 2012 Elsevier Inc. All rights reserved.

Multi-threaded Event Processing with DANA

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

David Lawrence; Elliott Wolin

2007-05-14

The C++ data analysis framework DANA has been written to support the next generation of Nuclear Physics experiments at Jefferson Lab commensurate with the anticipated 12GeV upgrade. The DANA framework was designed to allow multi-threaded event processing with a minimal impact on developers of reconstruction software. This document describes how DANA implements multi-threaded event processing and compares it to simply running multiple instances of a program. Also presented are relative reconstruction rates for Pentium4, Xeon, and Opteron based machines.

Integrated Predictive Tools for Customizing Microstructure and Material Properties of Additively Manufactured Aerospace Components

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

Radhakrishnan, Balasubramaniam; Fattebert, Jean-Luc; Gorti, Sarma B.

Additive Manufacturing (AM) refers to a process by which digital three-dimensional (3-D) design data is converted to build up a component by depositing material layer-by-layer. United Technologies Corporation (UTC) is currently involved in fabrication and certification of several AM aerospace structural components made from aerospace materials. This is accomplished by using optimized process parameters determined through numerous design-of-experiments (DOE)-based studies. Certification of these components is broadly recognized as a significant challenge, with long lead times, very expensive new product development cycles and very high energy consumption. Because of these challenges, United Technologies Research Center (UTRC), together with UTC business unitsmore » have been developing and validating an advanced physics-based process model. The specific goal is to develop a physics-based framework of an AM process and reliably predict fatigue properties of built-up structures as based on detailed solidification microstructures. Microstructures are predicted using process control parameters including energy source power, scan velocity, deposition pattern, and powder properties. The multi-scale multi-physics model requires solution and coupling of governing physics that will allow prediction of the thermal field and enable solution at the microstructural scale. The state-of-the-art approach to solve these problems requires a huge computational framework and this kind of resource is only available within academia and national laboratories. The project utilized the parallel phase-fields codes at Oak Ridge National Laboratory (ORNL) and Lawrence Livermore National Laboratory (LLNL), along with the high-performance computing (HPC) capabilities existing at the two labs to demonstrate the simulation of multiple dendrite growth in threedimensions (3-D). The LLNL code AMPE was used to implement the UTRC phase field model that was previously developed for a model binary alloy, and the simulation results were compared against the UTRC simulation results, followed by extension of the UTRC model to simulate multiple dendrite growth in 3-D. The ORNL MEUMAPPS code was used to simulate dendritic growth in a model ternary alloy with the same equilibrium solidification range as the Ni-base alloy 718 using realistic model parameters, including thermodynamic integration with a Calphad based model for the ternary alloy. Implementation of the UTRC model in AMPE met with several numerical and parametric issues that were resolved and good comparison between the simulation results obtained by the two codes was demonstrated for two dimensional (2-D) dendrites. 3-D dendrite growth was then demonstrated with the AMPE code using nondimensional parameters obtained in 2-D simulations. Multiple dendrite growth in 2-D and 3-D were demonstrated using ORNL’s MEUMAPPS code using simple thermal boundary conditions. MEUMAPPS was then modified to incorporate the complex, time-dependent thermal boundary conditions obtained by UTRC’s thermal modeling of single track AM experiments to drive the phase field simulations. The results were in good agreement with UTRC’s experimental measurements.« less

Development of Antimicrobial Peptide Prediction Tool for Aquaculture Industries.

PubMed

Gautam, Aditi; Sharma, Asuda; Jaiswal, Sarika; Fatma, Samar; Arora, Vasu; Iquebal, M A; Nandi, S; Sundaray, J K; Jayasankar, P; Rai, Anil; Kumar, Dinesh

2016-09-01

Microbial diseases in fish, plant, animal and human are rising constantly; thus, discovery of their antidote is imperative. The use of antibiotic in aquaculture further compounds the problem by development of resistance and consequent consumer health risk by bio-magnification. Antimicrobial peptides (AMPs) have been highly promising as natural alternative to chemical antibiotics. Though AMPs are molecules of innate immune defense of all advance eukaryotic organisms, fish being heavily dependent on their innate immune defense has been a good source of AMPs with much wider applicability. Machine learning-based prediction method using wet laboratory-validated fish AMP can accelerate the AMP discovery using available fish genomic and proteomic data. Earlier AMP prediction servers are based on multi-phyla/species data, and we report here the world's first AMP prediction server in fishes. It is freely accessible at http://webapp.cabgrid.res.in/fishamp/ . A total of 151 AMPs related to fish collected from various databases and published literature were taken for this study. For model development and prediction, N-terminus residues, C-terminus residues and full sequences were considered. Best models were with kernels polynomial-2, linear and radial basis function with accuracy of 97, 99 and 97 %, respectively. We found that performance of support vector machine-based models is superior to artificial neural network. This in silico approach can drastically reduce the time and cost of AMP discovery. This accelerated discovery of lead AMP molecules having potential wider applications in diverse area like fish and human health as substitute of antibiotics, immunomodulator, antitumor, vaccine adjuvant and inactivator, and also for packaged food can be of much importance for industries.

AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

PubMed

Chen, Peili; Li, Yan Chun; Toback, F Gary

2015-01-01

Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD). We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP)-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI) mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity

PubMed Central

Görner, Wolfram; Durchschlag, Erich; Martinez-Pastor, Maria Teresa; Estruch, Francisco; Ammerer, Gustav; Hamilton, Barbara; Ruis, Helmut; Schüller, Christoph

1998-01-01

Msn2p and the partially redundant factor Msn4p are key regulators of stress-responsive gene expression in Saccharomyces cerevisiae. They are required for the transcription of a number of genes coding for proteins with stress-protective functions. Both Msn2p and Msn4p are Cys2His2 zinc finger proteins and bind to the stress response element (STRE). In vivo footprinting studies show that the occupation of STREs is enhanced in stressed cells and dependent on the presence of Msn2p and Msn4p. Both factors accumulate in the nucleus under stress conditions, such as heat shock, osmotic stress, carbon-source starvation, and in the presence of ethanol or sorbate. Stress-induced nuclear localization was found to be rapid, reversible, and independent of protein synthesis. Nuclear localization of Msn2p and Msn4p was shown to be correlated inversely to cAMP levels and protein kinase A (PKA) activity. A region with significant homologies shared between Msn2p and Msn4p is sufficient to confer stress-regulated localization to a SV40–NLS–GFP fusion protein. Serine to alanine or aspartate substitutions in a conserved PKA consensus site abolished cAMP-driven nuclear export and cytoplasmic localization in unstressed cells. We propose stress and cAMP-regulated intracellular localization of Msn2p to be a key step in STRE-dependent transcription and in the general stress response. PMID:9472026

A journey from nuclear criticality methods to high energy density radflow experiments

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

Urbatsch, Todd James

Los Alamos National Laboratory is a nuclear weapons laboratory supporting our nation's defense. In support of this mission is a high energy-density physics program in which we design and execute experiments to study radiationhydrodynamics phenomena and improve the predictive capability of our largescale multi-physics software codes on our big-iron computers. The Radflow project’s main experimental effort now is to understand why we haven't been able to predict opacities on Sandia National Laboratory's Z-machine. We are modeling an increasing fraction of the Z-machine's dynamic hohlraum to find multi-physics explanations for the experimental results. Further, we are building an entirely different opacitymore » platform on Lawrence Livermore National Laboratory's National Ignition Facility (NIF), which is set to get results early 2017. Will the results match our predictions, match the Z-machine, or give us something entirely different? The new platform brings new challenges such as designing hohlraums and spectrometers. The speaker will recount his history, starting with one-dimensional Monte Carlo nuclear criticality methods in graduate school, radiative transfer methods research and software development for his first 16 years at LANL, and, now, radflow technology and experiments. Who knew that the real world was more than just radiation transport? Experiments aren't easy, but they sure are fun.« less

Inhibitory effects of ginseng total saponin on up-regulation of cAMP pathway induced by repeated administration of morphine.

PubMed

Seo, Jeong-Ju; Lee, Jae-Woong; Lee, Wan-Kyu; Hong, Jin-Tae; Lee, Chong-Kil; Lee, Myung-Koo; Oh, Ki-Wan

2008-02-01

We have reported that ginseng total saponin (GTS) inhibited the development of physical and psychological dependence on morphine. However, the possible molecular mechanisms of GTS are unclear. Therefore, this study was undertaken to understand the possible molecular mechanism of GTS on the inhibitory effects of morphine-induced dependence. It has been reported that the up-regulated cAMP pathway in the LC of the mouse brain after repeated administration of morphine contributes to the feature of withdrawals. GTS inhibited up-regulation of cAMP pathway in the LC after repeated administration of morphine in this experiment. GTS inhibited cAMP levels and protein expression of protein kinase A (PKA). In addition, GTS inhibited the increase of cAMP response element binding protein (CREB) phosphorylation. Therefore, we conclude that the inhibitory effects of GTS on morphine-induced dependence might be mediated by the inhibition of cAMP pathway.

Design and implementation of atmospheric multi-parameter sensor for UAVs

NASA Astrophysics Data System (ADS)

Yu, F.; Zhao, Y.; Chen, G.; Liu, Y.; Han, Y.

2017-12-01

With the rapid development of industry and the increase of cars in developing countries, air pollutants have caused a series of environmental issues such as haze and smog. However, air pollution is a process of surface-to-air mass exchange, and various kinds of atmospheric factors have close association with aerosol concentration, such as temperature, humidity, etc. Vertical distributions of aerosol in the region provide an important clue to reveal the exchange mechanism in the atmosphere between atmospheric boundary layer and troposphere. Among the various kinds of flying platforms, unmanned aerial vehicles (UAVs) shows more advantages in vertical measurement of aerosol owned to its flexibility and low cost. However, only few sensors could be mounted on the UAVs because of the limited size and power requirement. Here, a light-weight, low-power atmospheric multi-parameter sensor (AMPS) is proposed and could be mounted on several kinds of UAV platforms. The AMPS integrates multi-sensors, which are the laser aerosol particle sensor, the temperature probe, the humidity probe and the pressure probe, in order to simultaneously sample the vertical distribution characters of aerosol particle concentration, temperature, relative humidity and atmospheric pressure. The data from the sensors are synchronized by a proposed communication mechanism based on GPS. Several kinds of housing are designed to accommodate the different payload requirements of UAVs in size and weight. The experiments were carried out with AMPS mounted on three kinds of flying platforms. The results shows that the power consumption is less than 1.3 W, with relatively high accuracy in temperature (±0.1°C), relative humidity (±0.8%RH), PM2.5 (<20%) and PM10 (<20%). Vertical profiles of PM2.5 and PM10 concentrations were observed simultaneously by the AMPS three times every day in five days. The results revealed the significant correlation between the aerosol particle concentration and atmospheric parameters. With low cost and flexibility, AMPS for UAVs provides an effective way to explore the properties of aerosol vertical distribution, and to monitor air pollutants flexibly.

Multi-sensor radiation detection, imaging, and fusion

NASA Astrophysics Data System (ADS)

Vetter, Kai

2016-01-01

Glenn Knoll was one of the leaders in the field of radiation detection and measurements and shaped this field through his outstanding scientific and technical contributions, as a teacher, his personality, and his textbook. His Radiation Detection and Measurement book guided me in my studies and is now the textbook in my classes in the Department of Nuclear Engineering at UC Berkeley. In the spirit of Glenn, I will provide an overview of our activities at the Berkeley Applied Nuclear Physics program reflecting some of the breadth of radiation detection technologies and their applications ranging from fundamental studies in physics to biomedical imaging and to nuclear security. I will conclude with a discussion of our Berkeley Radwatch and Resilient Communities activities as a result of the events at the Dai-ichi nuclear power plant in Fukushima, Japan more than 4 years ago.

Extreme Light Infrastructure - Nuclear Physics pillar (ELI-NP) : new horizons in physics with high power lasers and brilliant gamma beams.

PubMed

Gales, Sydney; Tanaka, Kazuo A; Balabanski, D L; Negoita, Florin; Stutman, D; Ur, Calin Alexander; Tesileanu, Ovidiu; Ursescu, Daniel; Ghita, Dan Gabriel; Andrei, I; Ataman, Stefan; Cernaianu, M O; D'Alessi, L; Dancus, I; Diaconescu, B; Djourelov, N; Filipescu, D; Ghenuche, P; Matei, C; Seto Kei, K; Zeng, M; Zamfir, Victor Nicolae

2018-06-28

The European Strategic Forum for Research Infrastructures (ESFRI) has selected in 2006 a proposal based on ultra-intense laser elds with intensities reaching up to 10221023 W/cm2 called \\ELI" for Extreme Light Infrastructure. The construction of a large-scale laser-centred, distributed pan-European research infrastructure, involving beyond the state-of-the-art ultra-short and ultra-intense laser technologies, received the approval for funding in 2011 2012. The three pillars of the ELI facility are being built in Czech Republic, Hungary and Romania. The Romanian pillar is ELI-Nuclear Physics (ELI-NP). The new facility is intended to serve a broad national, European and International science community. Its mission covers scientic research at the frontier of knowledge involving two domains. The rst one is laser-driven experiments related to nuclear physics, strong-eld quantum electrodynamics and associated vacuum eects. The second is based on a Comptonbackscattering high-brilliance and intense low-energy gamma beam (< 20 MeV), a marriage of laser and accelerator technology which will allow us to investigate nuclear structure and reactions as well as nuclear astrophysics with unprecedented resolution and accuracy. In addition to fundamental themes, a large number of applications with signicant societal impact are being developed. The ELI-NP research centre will be located in Magurele near Bucharest, Romania. The project is implemented by \\Horia Hulubei" National Institute for Physics and Nuclear Engineering (IFIN-HH). The project started in January 2013 and the new facility will be fully operational by the end of 2019. After a short introduction to multi-PW lasers and Multi-MeV brilliant gamma beam scientic and technical description of the future ELI-NP facility as well as the present status of its implementation of ELI-NP, will be presented. The science and examples of societal applications at reach with these new probes will be discussed with a special focus on day-one experiments and associated novel instrumentation. © 2018 IOP Publishing Ltd.

Science based integrated approach to advanced nuclear fuel development - integrated multi-scale multi-physics hierarchical modeling and simulation framework Part III: cladding

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

Tome, Carlos N; Caro, J A; Lebensohn, R A

2010-01-01

Advancing the performance of Light Water Reactors, Advanced Nuclear Fuel Cycles, and Advanced Reactors, such as the Next Generation Nuclear Power Plants, requires enhancing our fundamental understanding of fuel and materials behavior under irradiation. The capability to accurately model the nuclear fuel systems to develop predictive tools is critical. Not only are fabrication and performance models needed to understand specific aspects of the nuclear fuel, fully coupled fuel simulation codes are required to achieve licensing of specific nuclear fuel designs for operation. The backbone of these codes, models, and simulations is a fundamental understanding and predictive capability for simulating themore » phase and microstructural behavior of the nuclear fuel system materials and matrices. In this paper we review the current status of the advanced modeling and simulation of nuclear reactor cladding, with emphasis on what is available and what is to be developed in each scale of the project, how we propose to pass information from one scale to the next, and what experimental information is required for benchmarking and advancing the modeling at each scale level.« less

Structural basis of DNA folding and recognition in an AMP-DNA aptamer complex: distinct architectures but common recognition motifs for DNA and RNA aptamers complexed to AMP.

PubMed

Lin, C H; Patel, D J

1997-11-01

Structural studies by nuclear magnetic resonance (NMR) of RNA and DNA aptamer complexes identified through in vitro selection and amplification have provided a wealth of information on RNA and DNA tertiary structure and molecular recognition in solution. The RNA and DNA aptamers that target ATP (and AMP) with micromolar affinity exhibit distinct binding site sequences and secondary structures. We report below on the tertiary structure of the AMP-DNA aptamer complex in solution and compare it with the previously reported tertiary structure of the AMP-RNA aptamer complex in solution. The solution structure of the AMP-DNA aptamer complex shows, surprisingly, that two AMP molecules are intercalated at adjacent sites within a rectangular widened minor groove. Complex formation involves adaptive binding where the asymmetric internal bubble of the free DNA aptamer zippers up through formation of a continuous six-base mismatch segment which includes a pair of adjacent three-base platforms. The AMP molecules pair through their Watson-Crick edges with the minor groove edges of guanine residues. These recognition G.A mismatches are flanked by sheared G.A and reversed Hoogsteen G.G mismatch pairs. The AMP-DNA aptamer and AMP-RNA aptamer complexes have distinct tertiary structures and binding stoichiometries. Nevertheless, both complexes have similar structural features and recognition alignments in their binding pockets. Specifically, AMP targets both DNA and RNA aptamers by intercalating between purine bases and through identical G.A mismatch formation. The recognition G.A mismatch stacks with a reversed Hoogsteen G.G mismatch in one direction and with an adenine base in the other direction in both complexes. It is striking that DNA and RNA aptamers selected independently from libraries of 10(14) molecules in each case utilize identical mismatch alignments for molecular recognition with micromolar affinity within binding-site pockets containing common structural elements.

The Chemical Basis for the Origin of the Genetic Code and the Process of Protein Synthesis

NASA Technical Reports Server (NTRS)

Lacey, James C., Jr.

1990-01-01

A model for the origin of protein synthesis. The essential features of the model are that 5'-AMP and perhaps other monoribonucleotides can serve as catalysts for the selective synthesis of L-based peptides. A unique set of characteristics of 5'-AMP is responsible for the selective catalysts and these characteristics are described in detail. The model involves the formation of diesters as intermediates and selectivity for use of the L-isomer occurs principally at the step of forming the diester. However, in the formation of acetyl phenylalanine-AMP monoester there is a selectivity for esterification by the D-isomer. Data showing this selectivity is presented. This selectivity for D-isomer disappears after the first step. The identity was confirmed of all four of possible diesters of acetyl-D- and -L phenylaline with 5'-AMP by nuclear magnetic resonance (NMR). The data using flourescence and NMR show the Trp ring can associate with the adenine ring more strongly when the D-isomer is in the 2' position than it can when in the 3' position. These same data also suggest a molecular mechanisim for the faster esterificaton of 5'-AMP by acetyl-D-phenylaline. Some new data is also presented on the possible structure of the 2' isomer of acetyl-D-tryptophan-AMP monoester. The HPLC elution times of all four possible acetyl diphenylalanine esters of 5'-AMP were studied, these peptidyl esters will be products in the studies of peptide formation on the ribose of 5'-AMP. Other studies were on the rate of synthesis and the identity of the product when producing 3'Ac-Phe-2'tBOC-Phe-AMP diester. HPLC purification and identification of this product were accomplished.

C++ Coding Standards for the AMP Project

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

Evans, Thomas M; Clarno, Kevin T

2009-09-01

This document provides an initial starting point to define the C++ coding standards used by the AMP nuclear fuel performance integrated code project and a part of AMP's software development process. This document draws from the experiences, and documentation [1], of the developers of the Marmot Project at Los Alamos National Laboratory. Much of the software in AMP will be written in C++. The power of C++ can be abused easily, resulting in code that is difficult to understand and maintain. This document gives the practices that should be followed on the AMP project for all new code that ismore » written. The intent is not to be onerous but to ensure that the code can be readily understood by the entire code team and serve as a basis for collectively defining a set of coding standards for use in future development efforts. At the end of the AMP development in fiscal year (FY) 2010, all developers will have experience with the benefits, restrictions, and limitations of the standards described and will collectively define a set of standards for future software development. External libraries that AMP uses do not have to meet these requirements, although we encourage external developers to follow these practices. For any code of which AMP takes ownership, the project will decide on any changes on a case-by-case basis. The practices that we are using in the AMP project have been in use in the Denovo project [2] for several years. The practices build on those given in References [3-5]; the practices given in these references should also be followed. Some of the practices given in this document can also be found in [6].« less

Solution of multi-center molecular integrals of Slater-type orbitals

NASA Technical Reports Server (NTRS)

Tai, H.

1989-01-01

The troublesome multi-center molecular integrals of Slater-type orbitals (STO) in molecular physics calculations can be evaluated by using the Fourier transform and proper coupling of the two center exchange integrals. A numerical integration procedure is then readily rendered to the final expression in which the integrand consists of well known special functions of arguments containing the geometrical arrangement of the nuclear centers and the exponents of the atomic orbitals. A practical procedure was devised for the calculation of a general multi-center molecular integrals coupling arbitrary Slater-type orbitals. Symmetry relations and asymptotic conditions are discussed. Explicit expressions of three-center one-electron nuclear-attraction integrals and four-center two-electron repulsion integrals for STO of principal quantum number n=2 are listed. A few numerical results are given for the purpose of comparison.

Contribution of large-scale midlatitude disturbances to hourly precipitation extremes in the United States

NASA Astrophysics Data System (ADS)

Barbero, Renaud; Abatzoglou, John T.; Fowler, Hayley J.

2018-02-01

Midlatitude synoptic weather regimes account for a substantial portion of annual precipitation accumulation as well as multi-day precipitation extremes across parts of the United States (US). However, little attention has been devoted to understanding how synoptic-scale patterns contribute to hourly precipitation extremes. A majority of 1-h annual maximum precipitation (AMP) across the western US were found to be linked to two coherent midlatitude synoptic patterns: disturbances propagating along the jet stream, and cutoff upper-level lows. The influence of these two patterns on 1-h AMP varies geographically. Over 95% of 1-h AMP along the western coastal US were coincident with progressive midlatitude waves embedded within the jet stream, while over 30% of 1-h AMP across the interior western US were coincident with cutoff lows. Between 30-60% of 1-h AMP were coincident with the jet stream across the Ohio River Valley and southeastern US, whereas a a majority of 1-h AMP over the rest of central and eastern US were not found to be associated with either midlatitude synoptic features. Composite analyses for 1-h AMP days coincident to cutoff lows and jet stream show that an anomalous moisture flux and upper-level dynamics are responsible for initiating instability and setting up an environment conducive to 1-h AMP events. While hourly precipitation extremes are generally thought to be purely convective in nature, this study shows that large-scale dynamics and baroclinic disturbances may also contribute to precipitation extremes on sub-daily timescales.

CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: A new mammalian circadian oscillator model including the cAMP module

NASA Astrophysics Data System (ADS)

Wang, Jun-Wei; Zhou, Tian-Shou

2009-12-01

In this paper, we develop a new mathematical model for the mammalian circadian clock, which incorporates both transcriptional/translational feedback loops (TTFLs) and a cAMP-mediated feedback loop. The model shows that TTFLs and cAMP signalling cooperatively drive the circadian rhythms. It reproduces typical experimental observations with qualitative similarities, e.g. circadian oscillations in constant darkness and entrainment to light-dark cycles. In addition, it can explain the phenotypes of cAMP-mutant and Rev-erbα-/--mutant mice, and help us make an experimentally-testable prediction: oscillations may be rescued when arrhythmic mice with constitutively low concentrations of cAMP are crossed with Rev-erbα-/- mutant mice. The model enhances our understanding of the mammalian circadian clockwork from the viewpoint of the entire cell.

The impact of (n, γ) reaction rate uncertainties of unstable isotopes near N = 50 on the i-process nucleosynthesis in He-shell flash white dwarfs

NASA Astrophysics Data System (ADS)

Denissenkov, Pavel; Perdikakis, Georgios; Herwig, Falk; Schatz, Hendrik; Ritter, Christian; Pignatari, Marco; Jones, Samuel; Nikas, Stylianos; Spyrou, Artemis

2018-05-01

The first-peak s-process elements Rb, Sr, Y and Zr in the post-AGB star Sakurai's object (V4334 Sagittarii) have been proposed to be the result of i-process nucleosynthesis in a post-AGB very-late thermal pulse event. We estimate the nuclear physics uncertainties in the i-process model predictions to determine whether the remaining discrepancies with observations are significant and point to potential issues with the underlying astrophysical model. We find that the dominant source in the nuclear physics uncertainties are predictions of neutron capture rates on unstable neutron rich nuclei, which can have uncertainties of more than a factor 20 in the band of the i-process. We use a Monte Carlo variation of 52 neutron capture rates and a 1D multi-zone post-processing model for the i-process in Sakurai's object to determine the cumulative effect of these uncertainties on the final elemental abundance predictions. We find that the nuclear physics uncertainties are large and comparable to observational errors. Within these uncertainties the model predictions are consistent with observations. A correlation analysis of the results of our MC simulations reveals that the strongest impact on the predicted abundances of Rb, Sr, Y and Zr is made by the uncertainties in the (n, γ) reaction rates of 85Br, 86Br, 87Kr, 88Kr, 89Kr, 89Rb, 89Sr, and 92Sr. This conclusion is supported by a series of multi-zone simulations in which we increased and decreased to their maximum and minimum limits one or two reaction rates per run. We also show that simple and fast one-zone simulations should not be used instead of more realistic multi-zone stellar simulations for nuclear sensitivity and uncertainty studies of convective–reactive processes. Our findings apply more generally to any i-process site with similar neutron exposure, such as rapidly accreting white dwarfs with near-solar metallicities.

A Rapid and Quantitative Flow Cytometry Method for the Analysis of Membrane Disruptive Antimicrobial Activity.

PubMed

O'Brien-Simpson, Neil M; Pantarat, Namfon; Attard, Troy J; Walsh, Katrina A; Reynolds, Eric C

2016-01-01

We describe a microbial flow cytometry method that quantifies within 3 hours antimicrobial peptide (AMP) activity, termed Minimum Membrane Disruptive Concentration (MDC). Increasing peptide concentration positively correlates with the extent of bacterial membrane disruption and the calculated MDC is equivalent to its MBC. The activity of AMPs representing three different membranolytic modes of action could be determined for a range of Gram positive and negative bacteria, including the ESKAPE pathogens, E. coli and MRSA. By using the MDC50 concentration of the parent AMP, the method provides high-throughput, quantitative screening of AMP analogues. A unique feature of the MDC assay is that it directly measures peptide/bacteria interactions and lysed cell numbers rather than bacteria survival as with MIC and MBC assays. With the threat of multi-drug resistant bacteria, this high-throughput MDC assay has the potential to aid in the development of novel antimicrobials that target bacteria with improved efficacy.

Advanced Modular Power Approach to Affordable, Supportable Space Systems

NASA Technical Reports Server (NTRS)

Oeftering, Richard C.; Kimnach, Greg L.; Fincannon, James; Mckissock,, Barbara I.; Loyselle, Patricia L.; Wong, Edmond

2013-01-01

Recent studies of missions to the Moon, Mars and Near Earth Asteroids (NEA) indicate that these missions often involve several distinct separately launched vehicles that must ultimately be integrated together in-flight and operate as one unit. Therefore, it is important to see these vehicles as elements of a larger segmented spacecraft rather than separate spacecraft flying in formation. The evolution of large multi-vehicle exploration architecture creates the need (and opportunity) to establish a global power architecture that is common across all vehicles. The Advanced Exploration Systems (AES) Modular Power System (AMPS) project managed by NASA Glenn Research Center (GRC) is aimed at establishing the modular power system architecture that will enable power systems to be built from a common set of modular building blocks. The project is developing, demonstrating and evaluating key modular power technologies that are expected to minimize non-recurring development costs, reduce recurring integration costs, as well as, mission operational and support costs. Further, modular power is expected to enhance mission flexibility, vehicle reliability, scalability and overall mission supportability. The AMPS project not only supports multi-vehicle architectures but should enable multi-mission capability as well. The AMPS technology development involves near term demonstrations involving developmental prototype vehicles and field demonstrations. These operational demonstrations not only serve as a means of evaluating modular technology but also provide feedback to developers that assure that they progress toward truly flexible and operationally supportable modular power architecture.

Additional hydrogen bonds and base-pair kinetics in the symmetrical AMP-DNA aptamer complex.

PubMed Central

Nonin-Lecomte, S; Lin, C H; Patel, D J

2001-01-01

The solution structure of an adenosine monophosphate (AMP)-DNA aptamer complex has been determined previously [Lin, C. H., and Patel, D. J. (1997) Chem. Biol. 4:817-832]. On a symmetrical aptamer complex containing the same binding loop, but with better resolved spectra, we have identified two additional hydrogen bond-mediated associations in the binding loop. One of these involves a rapidly exchanging G imino proton. The phosphate group of the AMP ligand was identified as the acceptor by comparison with other aptamer complexes. Imino proton exchange measurements also yielded the dissociation constants of the stem and binding loop base pairs. This study shows that nuclear magnetic resonance-based imino proton exchange is a good probe for detection of weak hydrogen-bond associations. PMID:11721004

High-resolution coupled physics solvers for analysing fine-scale nuclear reactor design problems.

PubMed

Mahadevan, Vijay S; Merzari, Elia; Tautges, Timothy; Jain, Rajeev; Obabko, Aleksandr; Smith, Michael; Fischer, Paul

2014-08-06

An integrated multi-physics simulation capability for the design and analysis of current and future nuclear reactor models is being investigated, to tightly couple neutron transport and thermal-hydraulics physics under the SHARP framework. Over several years, high-fidelity, validated mono-physics solvers with proven scalability on petascale architectures have been developed independently. Based on a unified component-based architecture, these existing codes can be coupled with a mesh-data backplane and a flexible coupling-strategy-based driver suite to produce a viable tool for analysts. The goal of the SHARP framework is to perform fully resolved coupled physics analysis of a reactor on heterogeneous geometry, in order to reduce the overall numerical uncertainty while leveraging available computational resources. The coupling methodology and software interfaces of the framework are presented, along with verification studies on two representative fast sodium-cooled reactor demonstration problems to prove the usability of the SHARP framework.

High-resolution coupled physics solvers for analysing fine-scale nuclear reactor design problems

PubMed Central

Mahadevan, Vijay S.; Merzari, Elia; Tautges, Timothy; Jain, Rajeev; Obabko, Aleksandr; Smith, Michael; Fischer, Paul

2014-01-01

An integrated multi-physics simulation capability for the design and analysis of current and future nuclear reactor models is being investigated, to tightly couple neutron transport and thermal-hydraulics physics under the SHARP framework. Over several years, high-fidelity, validated mono-physics solvers with proven scalability on petascale architectures have been developed independently. Based on a unified component-based architecture, these existing codes can be coupled with a mesh-data backplane and a flexible coupling-strategy-based driver suite to produce a viable tool for analysts. The goal of the SHARP framework is to perform fully resolved coupled physics analysis of a reactor on heterogeneous geometry, in order to reduce the overall numerical uncertainty while leveraging available computational resources. The coupling methodology and software interfaces of the framework are presented, along with verification studies on two representative fast sodium-cooled reactor demonstration problems to prove the usability of the SHARP framework. PMID:24982250

The ATLAS multi-user upgrade and potential applications

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

Mustapha, B.; Nolen, J. A.; Savard, G.

With the recent integration of the CARIBU-EBIS charge breeder into the ATLAS accelerator system to provide for more pure and efficient charge breeding of radioactive beams, a multi-user upgrade of the ATLAS facility is being proposed to serve multiple users simultaneously. ATLAS was the first superconducting ion linac in the world and is the US DOE low-energy Nuclear Physics National User Facility. The proposed upgrade will take advantage of the continuous-wave nature of ATLAS and the pulsed nature of the EBIS charge breeder in order to simultaneously accelerate two beams with very close mass-to-charge ratios; one stable from the existingmore » ECR ion source and one radioactive from the newly commissioned EBIS charge breeder. In addition to enhancing the nuclear physics program, beam extraction at different points along the linac will open up the opportunity for other potential applications; for instance, material irradiation studies at ~ 1 MeV/u and isotope production at ~ 6 MeV/u or at the full ATLAS energy of ~ 15 MeV/u. The concept and proposed implementation of the ATLAS multi-user upgrade will be presented. Future plans to enhance the flexibility of this upgrade will also be presented.« less

The ATLAS multi-user upgrade and potential applications

NASA Astrophysics Data System (ADS)

Mustapha, B.; Nolen, J. A.; Savard, G.; Ostroumov, P. N.

2017-12-01

With the recent integration of the CARIBU-EBIS charge breeder into the ATLAS accelerator system to provide for more pure and efficient charge breeding of radioactive beams, a multi-user upgrade of the ATLAS facility is being proposed to serve multiple users simultaneously. ATLAS was the first superconducting ion linac in the world and is the US DOE low-energy Nuclear Physics National User Facility. The proposed upgrade will take advantage of the continuous-wave nature of ATLAS and the pulsed nature of the EBIS charge breeder in order to simultaneously accelerate two beams with very close mass-to-charge ratios; one stable from the existing ECR ion source and one radioactive from the newly commissioned EBIS charge breeder. In addition to enhancing the nuclear physics program, beam extraction at different points along the linac will open up the opportunity for other potential applications; for instance, material irradiation studies at ~1 MeV/u, isotope production and radiobiological studies at ~6 MeV/u and at the full ATLAS energy of ~15 MeV/u. The concept and proposed implementation of the ATLAS multi-user upgrade will be discussed. Future plans to enhance the flexibility of this upgrade will be presented.

Propagation of neutron-reaction uncertainties through multi-physics models of novel LWR's

NASA Astrophysics Data System (ADS)

Hernandez-Solis, Augusto; Sjöstrand, Henrik; Helgesson, Petter

2017-09-01

The novel design of the renewable boiling water reactor (RBWR) allows a breeding ratio greater than unity and thus, it aims at providing for a self-sustained fuel cycle. The neutron reactions that compose the different microscopic cross-sections and angular distributions are uncertain, so when they are employed in the determination of the spatial distribution of the neutron flux in a nuclear reactor, a methodology should be employed to account for these associated uncertainties. In this work, the Total Monte Carlo (TMC) method is used to propagate the different neutron-reactions (as well as angular distributions) covariances that are part of the TENDL-2014 nuclear data (ND) library. The main objective is to propagate them through coupled neutronic and thermal-hydraulic models in order to assess the uncertainty of important safety parameters related to multi-physics, such as peak cladding temperature along the axial direction of an RBWR fuel assembly. The objective of this study is to quantify the impact that ND covariances of important nuclides such as U-235, U-238, Pu-239 and the thermal scattering of hydrogen in H2O have in the deterministic safety analysis of novel nuclear reactors designs.

A journey from nuclear criticality methods to high energy density radflow experiments

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

Urbatsch, Todd James

Los Alamos National Laboratory is a nuclear weapons laboratory supporting our nation's defense. In support of this mission is a high energy-density physics program in which we design and execute experiments to study radiationhydrodynamics phenomena and improve the predictive capability of our largescale multi-physics software codes on our big-iron computers. The Radflow project’s main experimental effort now is to understand why we haven't been able to predict opacities on Sandia National Laboratory's Z-machine. We are modeling an increasing fraction of the Z-machine's dynamic hohlraum to find multi-physics explanations for the experimental results. Further, we are building an entirely different opacitymore » platform on Lawrence Livermore National Laboratory's National Ignition Facility (NIF), which is set to get results early 2017. Will the results match our predictions, match the Z-machine, or give us something entirely different? The new platform brings new challenges such as designing hohlraums and spectrometers. The speaker will recount his history, starting with one-dimensional Monte Carlo nuclear criticality methods in graduate school, radiative transfer methods research and software development for his first 16 years at LANL, and, now, radflow technology and experiments. Who knew that the real world was more than just radiation transport? Experiments aren't easy and they are as saturated with politics as a presidential election, but they sure are fun.« less

Mapping the Free Energy Landscape of PKA Inhibition and Activation: A Double-Conformational Selection Model for the Tandem cAMP-Binding Domains of PKA RIα

PubMed Central

Akimoto, Madoka; McNicholl, Eric Tyler; Ramkissoon, Avinash; Moleschi, Kody; Taylor, Susan S.; Melacini, Giuseppe

2015-01-01

Protein Kinase A (PKA) is the major receptor for the cyclic adenosine monophosphate (cAMP) secondary messenger in eukaryotes. cAMP binds to two tandem cAMP-binding domains (CBD-A and -B) within the regulatory subunit of PKA (R), unleashing the activity of the catalytic subunit (C). While CBD-A in RIα is required for PKA inhibition and activation, CBD-B functions as a “gatekeeper” domain that modulates the control exerted by CBD-A. Preliminary evidence suggests that CBD-B dynamics are critical for its gatekeeper function. To test this hypothesis, here we investigate by Nuclear Magnetic Resonance (NMR) the two-domain construct RIα (91–379) in its apo, cAMP2, and C-bound forms. Our comparative NMR analyses lead to a double conformational selection model in which each apo CBD dynamically samples both active and inactive states independently of the adjacent CBD within a nearly degenerate free energy landscape. Such degeneracy is critical to explain the sensitivity of CBD-B to weak interactions with C and its high affinity for cAMP. Binding of cAMP eliminates this degeneracy, as it selectively stabilizes the active conformation within each CBD and inter-CBD contacts, which require both cAMP and W260. The latter is contributed by CBD-B and mediates capping of the cAMP bound to CBD-A. The inter-CBD interface is dispensable for intra-CBD conformational selection, but is indispensable for full activation of PKA as it occludes C-subunit recognition sites within CBD-A. In addition, the two structurally homologous cAMP-bound CBDs exhibit marked differences in their residual dynamics profiles, supporting the notion that conservation of structure does not necessarily imply conservation of dynamics. PMID:26618408

Multi-channel probes to understand fission dynamics

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

Mosby, Shea Morgan

2016-04-15

Explaining the origin of the elements is a major outstanding question in nuclear astrophysics. Observed elemental abundance distribution shows strong nuclear physics effects. In conclusion, neutron-induced reactions are important for nuclear astrophysics and applied fields in nuclear energy and security. LANSCE has a program to address many of these questions directly with neutron beams on (near-)stable nuclei. Increasing demand for correlated data to test details of fission models poses additional challenges. Possibilities exist to extend existing experimental efforts to radioactive beam facilities. Kinematic focusing from using inverse kinematics has potential to circumvent some challenges associated with measuring correlations between fissionmore » output channels.« less

Nuclear Thermal Propulsion (NTP) Development Activities at the NASA Marshall Space Flight Center - 2006 Accomplishments

NASA Technical Reports Server (NTRS)

Ballard, Richard O.

2007-01-01

In 2005-06, the Prometheus program funded a number of tasks at the NASA-Marshall Space Flight Center (MSFC) to support development of a Nuclear Thermal Propulsion (NTP) system for future manned exploration missions. These tasks include the following: 1. NTP Design Develop Test & Evaluate (DDT&E) Planning 2. NTP Mission & Systems Analysis / Stage Concepts & Engine Requirements 3. NTP Engine System Trade Space Analysis and Studies 4. NTP Engine Ground Test Facility Assessment 5. Non-Nuclear Environmental Simulator (NTREES) 6. Non-Nuclear Materials Fabrication & Evaluation 7. Multi-Physics TCA Modeling. This presentation is a overview of these tasks and their accomplishments

Advances in Geologic Disposal System Modeling and Application to Crystalline Rock

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

Mariner, Paul E.; Stein, Emily R.; Frederick, Jennifer M.

The Used Fuel Disposition Campaign (UFDC) of the U.S. Department of Energy (DOE) Office of Nuclear Energy (NE), Office of Fuel Cycle Technology (OFCT) is conducting research and development (R&D) on geologic disposal of used nuclear fuel (UNF) and high-level nuclear waste (HLW). Two of the high priorities for UFDC disposal R&D are design concept development and disposal system modeling (DOE 2011). These priorities are directly addressed in the UFDC Generic Disposal Systems Analysis (GDSA) work package, which is charged with developing a disposal system modeling and analysis capability for evaluating disposal system performance for nuclear waste in geologic mediamore » (e.g., salt, granite, clay, and deep borehole disposal). This report describes specific GDSA activities in fiscal year 2016 (FY 2016) toward the development of the enhanced disposal system modeling and analysis capability for geologic disposal of nuclear waste. The GDSA framework employs the PFLOTRAN thermal-hydrologic-chemical multi-physics code and the Dakota uncertainty sampling and propagation code. Each code is designed for massively-parallel processing in a high-performance computing (HPC) environment. Multi-physics representations in PFLOTRAN are used to simulate various coupled processes including heat flow, fluid flow, waste dissolution, radionuclide release, radionuclide decay and ingrowth, precipitation and dissolution of secondary phases, and radionuclide transport through engineered barriers and natural geologic barriers to the biosphere. Dakota is used to generate sets of representative realizations and to analyze parameter sensitivity.« less

Integral Full Core Multi-Physics PWR Benchmark with Measured Data

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

Forget, Benoit; Smith, Kord; Kumar, Shikhar

In recent years, the importance of modeling and simulation has been highlighted extensively in the DOE research portfolio with concrete examples in nuclear engineering with the CASL and NEAMS programs. These research efforts and similar efforts worldwide aim at the development of high-fidelity multi-physics analysis tools for the simulation of current and next-generation nuclear power reactors. Like all analysis tools, verification and validation is essential to guarantee proper functioning of the software and methods employed. The current approach relies mainly on the validation of single physic phenomena (e.g. critical experiment, flow loops, etc.) and there is a lack of relevantmore » multiphysics benchmark measurements that are necessary to validate high-fidelity methods being developed today. This work introduces a new multi-cycle full-core Pressurized Water Reactor (PWR) depletion benchmark based on two operational cycles of a commercial nuclear power plant that provides a detailed description of fuel assemblies, burnable absorbers, in-core fission detectors, core loading and re-loading patterns. This benchmark enables analysts to develop extremely detailed reactor core models that can be used for testing and validation of coupled neutron transport, thermal-hydraulics, and fuel isotopic depletion. The benchmark also provides measured reactor data for Hot Zero Power (HZP) physics tests, boron letdown curves, and three-dimensional in-core flux maps from 58 instrumented assemblies. The benchmark description is now available online and has been used by many groups. However, much work remains to be done on the quantification of uncertainties and modeling sensitivities. This work aims to address these deficiencies and make this benchmark a true non-proprietary international benchmark for the validation of high-fidelity tools. This report details the BEAVRS uncertainty quantification for the first two cycle of operations and serves as the final report of the project.« less

Essential Ingredients in Core-collapse Supernovae

DOE PAGES

Hix, William Raphael; Lentz, E. J.; Endeve, Eirik; ...

2014-03-27

Marking the inevitable death of a massive star, and the birth of a neutron star or black hole, core-collapse supernovae bring together physics at a wide range in spatial scales, from kilometer-sized hydrodynamic motions (eventually growing to gigameter scale) down to femtometer scale nuclear reactions. Carrying 10more » $$^{44}$$ joules of kinetic energy and a rich-mix of newly synthesized atomic nuclei, core-collapse supernovae are the preeminent foundries of the nuclear species which make up ourselves and our solar system. We will discuss our emerging understanding of the convectively unstable, neutrino-driven explosion mechanism, based on increasingly realistic neutrino-radiation hydrodynamic simulations that include progressively better nuclear and particle physics. Recent multi-dimensional models with spectral neutrino transport from several research groups, which slowly develop successful explosions for a range of progenitors, have motivated changes in our understanding of the neutrino reheating mechanism. In a similar fashion, improvements in nuclear physics, most notably explorations of weak interactions on nuclei and the nuclear equation of state, continue to refine our understanding of how supernovae explode. Recent progress on both the macroscopic and microscopic effects that affect core-collapse supernovae are discussed.« less

Atmospheric, Magnetospheric, and Plasmas in Space (AMPS) spacelab payload definition study, technical summary document

NASA Technical Reports Server (NTRS)

Keeley, J. T.

1976-01-01

Some 60 instrument candidates and 80 possible science investigations were evaluated. The early analysis emphasized the science aspect in terms of the functional requirements for each of the potential experiments identified by the AMPS science working group. These requirements were then used for the grouping of instruments into practical payloads which would fit the capabilities of the Shuttle/Spacelab. This analysis resulted in the definition of eleven different AMPS configurations. The data were then used to define a typical set of requirements for a flexible AMPS laboratory. The data gathered to this point showed that a planned sequential buildup of the laboratory would be necessary to meet both physical and funding limitations. This led to the definition of five strawman payloads by the science working group, which were used to establish a conceptual laboratory and to define preliminary design of a configuration which could satisfy AMPS needs during the early program period.

The cyclic AMP cascade is altered in the fragile X nervous system.

PubMed

Kelley, Daniel J; Davidson, Richard J; Elliott, Jamie L; Lahvis, Garet P; Yin, Jerry C P; Bhattacharyya, Anita

2007-09-26

Fragile X syndrome (FX), the most common heritable cause of mental retardation and autism, is a developmental disorder characterized by physical, cognitive, and behavioral deficits. FX results from a trinucleotide expansion mutation in the fmr1 gene that reduces levels of fragile X mental retardation protein (FMRP). Although research efforts have focused on FMRP's impact on mGluR signaling, how the loss of FMRP leads to the individual symptoms of FX is not known. Previous studies on human FX blood cells revealed alterations in the cyclic adenosine 3', 5'-monophosphate (cAMP) cascade. We tested the hypothesis that cAMP signaling is altered in the FX nervous system using three different model systems. Induced levels of cAMP in platelets and in brains of fmr1 knockout mice are substantially reduced. Cyclic AMP induction is also significantly reduced in human FX neural cells. Furthermore, cAMP production is decreased in the heads of FX Drosophila and this defect can be rescued by reintroduction of the dfmr gene. Our results indicate that a robust defect in cAMP production in FX is conserved across species and suggest that cAMP metabolism may serve as a useful biomarker in the human disease population. Reduced cAMP induction has implications for the underlying causes of FX and autism spectrum disorders. Pharmacological agents known to modulate the cAMP cascade may be therapeutic in FX patients and can be tested in these models, thus supplementing current efforts centered on mGluR signaling.

Architectures and methodologies for future deployment of multi-site Zettabyte-Exascale data handling platforms

NASA Astrophysics Data System (ADS)

Acín, V.; Bird, I.; Boccali, T.; Cancio, G.; Collier, I. P.; Corney, D.; Delaunay, B.; Delfino, M.; dell'Agnello, L.; Flix, J.; Fuhrmann, P.; Gasthuber, M.; Gülzow, V.; Heiss, A.; Lamanna, G.; Macchi, P.-E.; Maggi, M.; Matthews, B.; Neissner, C.; Nief, J.-Y.; Porto, M. C.; Sansum, A.; Schulz, M.; Shiers, J.

2015-12-01

Several scientific fields, including Astrophysics, Astroparticle Physics, Cosmology, Nuclear and Particle Physics, and Research with Photons, are estimating that by the 2020 decade they will require data handling systems with data volumes approaching the Zettabyte distributed amongst as many as 1018 individually addressable data objects (Zettabyte-Exascale systems). It may be convenient or necessary to deploy such systems using multiple physical sites. This paper describes the findings of a working group composed of experts from several

Applications of AMPS-1D for solar cell simulation

NASA Astrophysics Data System (ADS)

Zhu, Hong; Kalkan, Ali Kaan; Hou, Jingya; Fonash, Stephen J.

1999-03-01

The AMPS-1D PC computer program is now used by over 70 groups world-wide for detector and solar cell analysis. It has proved to be a very powerful tool in understanding device operation and physics for single crystal, poly-crystalline and amorphous structures. For example, AMPS-1D has been successful in explaining the "red kink" [1] and the "transient effect" in CdS/CIGS poly-crystalline solar cells. It has been used to show that thin film poly-Si structures, with reasonable light trapping, are capable of competitive solar cell conversion efficiencies. In the case of a-Si:H structures, it has been used, for example, to settle the discrepancies in bandgap measurement, to predict the effective QE>1 phenomenon later seen in these materials [2], to determine the relative roles of interface and bulk properties, and to point the direction toward 16% triple junction structures. In general AMPS-1D is used for cell and detector design, material parameter sensitivity studies, and parameter extraction. Recently we have shown that it can be used to determine optimum structure and light and voltage biasing conditions in the material parameter extraction function. Information on AMPS can be found at www.psu.edu/dept/AMPS/amps_web/AMPS.html and at other web sites set up by user groups.

YC-1 potentiates cAMP-induced CREB activation and nitric oxide production in alveolar macrophages.

PubMed

Hwang, Tsong-Long; Tang, Ming-Chi; Kuo, Liang-Mou; Chang, Wen-De; Chung, Pei-Jen; Chang, Ya-Wen; Fang, Yao-Ching

2012-04-15

Alveolar macrophages play significant roles in the pathogenesis of several inflammatory lung diseases. Increases in exhaled nitric oxide (NO) are well documented to reflect disease severity in the airway. In this study, we investigated the effect of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a known activator of soluble guanylyl cyclase, on prostaglandin (PG)E₁ (a stable PGE₂ analogue) and forskolin (a adenylate cyclase activator) induced NO production and inducible NO synthase (iNOS) expression in rat alveolar macrophages (NR8383). YC-1 did not directly cause NO production or iNOS expression, but drastically potentiated PGE₁- or forskolin-induced NO production and iNOS expression in NR8383 alveolar macrophages. Combination treatment with YC-1 and PGE₁ significantly increased phosphorylation of the cAMP response element-binding protein (CREB), but not nuclear factor (NF)-κB activation. The combined effect on NO production, iNOS expression, and CREB phosphorylation was reversed by a protein kinase (PK)A inhibitor (H89), suggesting that the potentiating functions were mediated through a cAMP/PKA signaling pathway. Consistent with this, cAMP analogues, but not the cGMP analogue, caused NO release, iNOS expression, and CREB activation. YC-1 treatment induced an increase in PGE₁-induced cAMP formation, which occurred through the inhibition of cAMP-specific phosphodiesterase (PDE) activity. Furthermore, the combination of rolipram (an inhibitor of PDE4), but not milronone (an inhibitor of PDE3), and PGE₁ also triggered NO production and iNOS expression. In summary, YC-1 potentiates PGE₁-induced NO production and iNOS expression in alveolar macrophages through inhibition of cAMP PDE activity and activation of the cAMP/PKA/CREB signaling pathway. Copyright © 2012 Elsevier Inc. All rights reserved.

Solar Wind Interaction with the Martian Upper Atmosphere at Early Mars/Extreme Solar Conditions

NASA Astrophysics Data System (ADS)

Dong, C.; Bougher, S. W.; Ma, Y.; Toth, G.; Lee, Y.; Nagy, A. F.; Tenishev, V.; Pawlowski, D. J.; Combi, M. R.

2014-12-01

The investigation of ion escape fluxes from Mars, resulting from the solar wind interaction with its upper atmosphere/ionosphere, is important due to its potential impact on the long-term evolution of Mars atmosphere (e.g., loss of water) over its history. In the present work, we adopt the 3-D Mars cold neutral atmosphere profiles (0 ~ 300 km) from the newly developed and validated Mars Global Ionosphere Thermosphere Model (M-GITM) and the 3-D hot oxygen profiles (100 km ~ 5 RM) from the exosphere Monte Carlo model Adaptive Mesh Particle Simulator (AMPS). We apply these 3-D model output fields into the 3-D BATS-R-US Mars multi-fluid MHD (MF-MHD) model (100 km ~ 20 RM) that can simulate the interplay between Mars upper atmosphere and solar wind by considering the dynamics of individual ion species. The multi-fluid MHD model solves separate continuity, momentum and energy equations for each ion species (H+, O+, O2+, CO2+). The M-GITM model together with the AMPS exosphere model take into account the effects of solar cycle and seasonal variations on both cold and hot neutral atmospheres. This feature allows us to investigate the corresponding effects on the Mars upper atmosphere ion escape by using a one-way coupling approach, i.e., both the M-GITM and AMPS model output fields are used as the input for the multi-fluid MHD model and the M-GITM is used as input into the AMPS exosphere model. In this study, we present M-GITM, AMPS, and MF-MHD calculations (1-way coupled) for 2.5 GYA conditions and/or extreme solar conditions for present day Mars (high solar wind velocities, high solar wind dynamic pressure, and high solar irradiance conditions, etc.). Present day extreme conditions may result in MF-MHD outputs that are similar to 2.5 GYA cases. The crustal field orientations are also considered in this study. By comparing estimates of past ion escape rates with the current ion loss rates to be returned by the MAVEN spacecraft (2013-2016), we can better constrain the total ion loss to space over Mars history, and thus enhance the science returned from the MAVEN mission.

Orphan Nuclear Receptor Small Heterodimer Partner Negatively Regulates Growth Hormone-mediated Induction of Hepatic Gluconeogenesis through Inhibition of Signal Transducer and Activator of Transcription 5 (STAT5) Transactivation*

PubMed Central

Kim, Yong Deuk; Li, Tiangang; Ahn, Seung-Won; Kim, Don-Kyu; Lee, Ji-Min; Hwang, Seung-Lark; Kim, Yong-Hoon; Lee, Chul-Ho; Lee, In-Kyu; Chiang, John Y. L.; Choi, Hueng-Sik

2012-01-01

Growth hormone (GH) is a key metabolic regulator mediating glucose and lipid metabolism. Ataxia telangiectasia mutated (ATM) is a member of the phosphatidylinositol 3-kinase superfamily and regulates cell cycle progression. The orphan nuclear receptor small heterodimer partner (SHP: NR0B2) plays a pivotal role in regulating metabolic processes. Here, we studied the role of ATM on GH-dependent regulation of hepatic gluconeogenesis in the liver. GH induced phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase gene expression in primary hepatocytes. GH treatment and adenovirus-mediated STAT5 overexpression in hepatocytes increased glucose production, which was blocked by a JAK2 inhibitor, AG490, dominant negative STAT5, and STAT5 knockdown. We identified a STAT5 binding site on the PEPCK gene promoter using reporter assays and point mutation analysis. Up-regulation of SHP by metformin-mediated activation of the ATM-AMP-activated protein kinase pathway led to inhibition of GH-mediated induction of hepatic gluconeogenesis, which was abolished by an ATM inhibitor, KU-55933. Immunoprecipitation studies showed that SHP physically interacted with STAT5 and inhibited STAT5 recruitment on the PEPCK gene promoter. GH-induced hepatic gluconeogenesis was decreased by either metformin or Ad-SHP, whereas the inhibition by metformin was abolished by SHP knockdown. Finally, the increase of hepatic gluconeogenesis following GH treatment was significantly higher in the liver of SHP null mice compared with that of wild-type mice. Overall, our results suggest that the ATM-AMP-activated protein kinase-SHP network, as a novel mechanism for regulating hepatic glucose homeostasis via a GH-dependent pathway, may be a potential therapeutic target for insulin resistance. PMID:22977252

Inquiring Minds

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Origin and evolution of circular waves and spirals in Dictyostelium discoideum territories.

PubMed

Pálsson, E; Cox, E C

1996-02-06

Randomly distributed Dictyostelium discoideum cells form cooperative territories by signaling to each other with cAMP. Cells initiate the process by sending out pulsatile signals, which propagate as waves. With time, circular and spiral patterns form. We show that by adding spatial and temporal noise to the levels of an important regulator of external cAMP levels, the cAMP phosphodiesterase inhibitor, we can explain the natural progression of the system from randomly firing cells to circular waves whose symmetries break to form double- and single- or multi-armed spirals. When phosphodiesterase inhibitor is increased with time, mimicking experimental data, the wavelength of the spirals shortens, and a proportion of them evolve into pairs of connected spirals. We compare these results to recent experiments, finding that the temporal and spatial correspondence between experiment and model is very close.

Evaluating experimental molecular physics studies of radiation damage in DNA*

NASA Astrophysics Data System (ADS)

Śmiałek, Małgorzata A.

2016-11-01

The field of Atomic and Molecular Physics (AMP) is a mature field exploring the spectroscopy, excitation, ionisation of atoms and molecules in all three phases. Understanding of the spectroscopy and collisional dynamics of AMP has been fundamental to the development and application of quantum mechanics and is applied across a broad range of disparate disciplines including atmospheric sciences, astrochemistry, combustion and environmental science, and in central to core technologies such as semiconductor fabrications, nanotechnology and plasma processing. In recent years the molecular physics also started significantly contributing to the area of the radiation damage at molecular level and thus cancer therapy improvement through both experimental and theoretical advances, developing new damage measurement and analysis techniques. It is therefore worth to summarise and highlight the most prominent findings from the AMP community that contribute towards better understanding of the fundamental processes in biologically-relevant systems as well as to comment on the experimental challenges that were met for more complex investigation targets. Contribution to the Topical Issue "Low-Energy Interactions related to Atmospheric and Extreme Conditions", edited by S. Ptasinska, M. Smialek-Telega, A. Milosavljevic, B. Sivaraman.

Hypothermia induced by adenosine 5'-monophosphate attenuates injury in an L-arginine-induced acute pancreatitis rat model.

PubMed

Wang, Yunlong; Guo, Weiting; Li, Yuan; Pan, Xinting; Lv, Wenshan; Cui, Lingling; Li, Changgui; Wang, Yangang; Yan, Shengli; Zhang, Jidong; Liu, Bin

2014-04-01

This study sought to investigate the effects of hypothermia induced by adenosine 5'-monophosphate (5'-AMP) on L-arginine (L-Arg)-induced acute pancreatitis in rats. The rats were divided into four groups: the control group, the acute pancreatitis group, the 5'-AMP pretreatment group, and the 5'-AMP posttreatment group. Rats in all groups, except for the control group, received two injections of 2.5 g/kg body weight (intraperitoneally) L-Arg, with an interval of 1 h between the injections. Subsequently, the rats were observed to assess whether hypothermia induced by 5'-AMP could effectively inhibit inflammation associated with L-Arg-induced acute pancreatitis in rats. Hypothermia induced by 5'-AMP produced protective effects in our acute pancreatitis model. These effects exhibited the following manifestations: (i) a significant reduction in rat mortality rates; (ii) a significant decrease in the occurrence of pancreatic edema; (iii) significant reductions in serum amylase (P < 0.001), interleukin-6 (P < 0.001), interleukin-1β (P < 0.001) and tumor necrosis factor-α (P < 0.001); (iv) the significant inhibition of nuclear factor-κB (NF-κB) activation in rats that were pre- and posttreated with 5'-AMP compared with rats that were only injected with L-Arg; and (v) significant decreases in the occurrence of pancreatic interstitial edema, inflammatory cell infiltration, hemorrhage, and acinar cell necrosis. Hypothermia induced by 5'-AMP could inhibit the acute inflammatory reaction and NF-κB activation associated with acute pancreatitis. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Taking a fresh look at boiling heat transfer on the road to improved nuclear economics and efficiency

DOE PAGES

Pointer, William David; Baglietto, Emilio

2016-05-01

Here, in the effort to reinvigorate innovation in the way we design, build, and operate the nuclear power generating stations of today and tomorrow, nothing can be taken for granted. Not even the seemingly familiar physics of boiling water. The Consortium for the Advanced Simulation of Light Water Reactors, or CASL, is focused on the deployment of advanced modeling and simulation capabilities to enable the nuclear industry to reduce uncertainties in the prediction of multi-physics phenomena and continue to improve the performance of today’s Light Water Reactors and their fuel. An important part of the CASL mission is the developmentmore » of a next generation thermal hydraulics simulation capability, integrating the history of engineering models based on experimental experience with the computing technology of the future.« less

DEPENDENCE OF X-RAY BURST MODELS ON NUCLEAR REACTION RATES

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

Cyburt, R. H.; Keek, L.; Schatz, H.

2016-10-20

X-ray bursts are thermonuclear flashes on the surface of accreting neutron stars, and reliable burst models are needed to interpret observations in terms of properties of the neutron star and the binary system. We investigate the dependence of X-ray burst models on uncertainties in (p, γ ), ( α , γ ), and ( α , p) nuclear reaction rates using fully self-consistent burst models that account for the feedbacks between changes in nuclear energy generation and changes in astrophysical conditions. A two-step approach first identified sensitive nuclear reaction rates in a single-zone model with ignition conditions chosen to matchmore » calculations with a state-of-the-art 1D multi-zone model based on the Kepler stellar evolution code. All relevant reaction rates on neutron-deficient isotopes up to mass 106 were individually varied by a factor of 100 up and down. Calculations of the 84 changes in reaction rate with the highest impact were then repeated in the 1D multi-zone model. We find a number of uncertain reaction rates that affect predictions of light curves and burst ashes significantly. The results provide insights into the nuclear processes that shape observables from X-ray bursts, and guidance for future nuclear physics work to reduce nuclear uncertainties in X-ray burst models.« less

The effect of adenosine 5'-monophosphate (AMP) on tenderness, microstructure and chemical-physical index of duck breast meat.

PubMed

Wang, Daoying; Deng, Shaoying; Zhang, Muhan; Geng, Zhiming; Sun, Chong; Bian, Huan; Xu, Weimin; Zhu, Yongzhi; Liu, Fang; Wu, Haihong

2016-03-30

Adenosine 5'-monophosphate (AMP) is often used in meat and poultry soups as a flavor enhancer (flavor modifier), or as food additives for specific nutritional purposes. Our previous research as well as evidence from others showed that actomyosin could be dissociated into myosin and actin by AMP in extracted muscle solution. However, there is no report available on the application of AMP to dissociate actomyosin and to improve meat tenderness. The objectives of this study were to evaluate the effect of AMP on duck meat tenderness and other quality traits and to explore the mechanism of the action of AMP on meat tenderness. Duck breast muscle was treated with 0, 10, 20, 30, 40 mmol L(-1) AMP at 5 °C for 10 h and examined for shear force, microstructure, actomyosin dissociation, myofibril fragmentation index (MFI), pH, water content, cooking loss, CIE* color (L*, a*, b*), inosine monophosphate (IMP) and free amino acid (FAA) contents. Results showed that shear force, cooking loss, L* and b* of the muscles significantly decreased after AMP treatment (P < 0.05); actomyosin dissociation, MFI, pH, water content, fiber diameter, sarcomere length, IMP and ammonia significantly increased (P < 0.05); no significant change in a* or other FAA content was observed (P > 0.05), and muscle shrinkage in transverse and longitudinal directions were restrained after AMP treatment. The results suggest that AMP could notably improve meat tenderness, and this effect was probably mainly through increasing muscle pH, promoting actomyosin dissociation and disrupting the Z-line; meanwhile, the conversion of AMP to IMP may contribute to the flavor of meat. © 2015 Society of Chemical Industry.

Voluntary running depreciates the requirement of Ca2+-stimulated cAMP signaling in synaptic potentiation and memory formation

PubMed Central

Zheng, Fei; Zhang, Ming; Ding, Qi; Sethna, Ferzin; Yan, Lily; Moon, Changjong; Yang, Miyoung

2016-01-01

Mental health and cognitive functions are influenced by both genetic and environmental factors. Although having active lifestyle with physical exercise improves learning and memory, how it interacts with the specific key molecular regulators of synaptic plasticity is largely unknown. Here, we examined the effects of voluntary running on long-term potentiation (LTP) and memory formation in mice lacking type 1 adenylyl cyclase (AC1), a neurospecific synaptic enzyme that contributes to Ca2+-stimulated cAMP production. Following 1 mo of voluntary running-wheel exercise, the impaired LTP and object recognition memory in AC1 knockout (KO) mice were significantly attenuated. Running up-regulated exon II mRNA level of BDNF (brain-derived neurotrophic factor), though it failed to increase exon I and IV mRNAs in the hippocampus of AC1 KO mice. Intrahippocampal infusion of recombinant BDNF was sufficient to rescue LTP and object recognition memory defects in AC1 KO mice. Therefore, voluntary running and exogenous BDNF application overcome the defective Ca2+-stimulated cAMP signaling. Our results also demonstrate that alteration in Ca2+-stimulated cAMP can affect the molecular outcome of physical exercise. PMID:27421897

Application of pulsed multi-ion irradiations in radiation damage research: A stochastic cluster dynamics simulation study

NASA Astrophysics Data System (ADS)

Hoang, Tuan L.; Nazarov, Roman; Kang, Changwoo; Fan, Jiangyuan

2018-07-01

Under the multi-ion irradiation conditions present in accelerated material-testing facilities or fission/fusion nuclear reactors, the combined effects of atomic displacements with radiation products may induce complex synergies in the structural materials. However, limited access to multi-ion irradiation facilities and the lack of computational models capable of simulating the evolution of complex defects and their synergies make it difficult to understand the actual physical processes taking place in the materials under these extreme conditions. In this paper, we propose the application of pulsed single/dual-beam irradiation as replacements for the expensive steady triple-beam irradiation to study radiation damages in materials under multi-ion irradiation.

Applications of Ultra-Intense, Short Laser Pulses

NASA Astrophysics Data System (ADS)

Ledingham, Ken W. D.

The high intensity laser production of electron, proton, ion and photon beams is reviewed particularly with respect to the laser-plasma interaction which drives the acceleration process. A number of applications for these intense short pulse beams is discussed e.g. ion therapy, PET isotope production and laser driven transmutation studies. The future for laser driven nuclear physics at the huge new, multi-petawatt proposed laser installation ELI in Bucharest is described. Many people believe this will take European nuclear research to the next level.

Fermilab | Science at Fermilab | Experiments & Projects | Energy Frontier

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Fermilab | Science at Fermilab | Experiments & Projects

Science.gov Websites

Go Science at Fermilab Fermilab and the Higgs Boson Frontiers of Particle Physics Experiments & Answers Submit a Question Frontiers of Particle Physics Benefits to Society Benefits to Society Medicine Inquiring Minds Questions About Physics Other High-Energy Physics Sites More About Particle Physics Library

Two-Step Multi-Physics Analysis of an Annular Linear Induction Pump for Fission Power Systems

NASA Technical Reports Server (NTRS)

Geng, Steven M.; Reid, Terry V.

2016-01-01

One of the key technologies associated with fission power systems (FPS) is the annular linear induction pump (ALIP). ALIPs are used to circulate liquid-metal fluid for transporting thermal energy from the nuclear reactor to the power conversion device. ALIPs designed and built to date for FPS project applications have not performed up to expectations. A unique, two-step approach was taken toward the multi-physics examination of an ALIP using ANSYS Maxwell 3D and Fluent. This multi-physics approach was developed so that engineers could investigate design variations that might improve pump performance. Of interest was to determine if simple geometric modifications could be made to the ALIP components with the goal of increasing the Lorentz forces acting on the liquid-metal fluid, which in turn would increase pumping capacity. The multi-physics model first calculates the Lorentz forces acting on the liquid metal fluid in the ALIP annulus. These forces are then used in a computational fluid dynamics simulation as (a) internal boundary conditions and (b) source functions in the momentum equations within the Navier-Stokes equations. The end result of the two-step analysis is a predicted pump pressure rise that can be compared with experimental data.

Modeling and simulation challenges pursued by the Consortium for Advanced Simulation of Light Water Reactors (CASL)

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

Turinsky, Paul J., E-mail: turinsky@ncsu.edu; Kothe, Douglas B., E-mail: kothe@ornl.gov

The Consortium for the Advanced Simulation of Light Water Reactors (CASL), the first Energy Innovation Hub of the Department of Energy, was established in 2010 with the goal of providing modeling and simulation (M&S) capabilities that support and accelerate the improvement of nuclear energy's economic competitiveness and the reduction of spent nuclear fuel volume per unit energy, and all while assuring nuclear safety. To accomplish this requires advances in M&S capabilities in radiation transport, thermal-hydraulics, fuel performance and corrosion chemistry. To focus CASL's R&D, industry challenge problems have been defined, which equate with long standing issues of the nuclear powermore » industry that M&S can assist in addressing. To date CASL has developed a multi-physics “core simulator” based upon pin-resolved radiation transport and subchannel (within fuel assembly) thermal-hydraulics, capitalizing on the capabilities of high performance computing. CASL's fuel performance M&S capability can also be optionally integrated into the core simulator, yielding a coupled multi-physics capability with untapped predictive potential. Material models have been developed to enhance predictive capabilities of fuel clad creep and growth, along with deeper understanding of zirconium alloy clad oxidation and hydrogen pickup. Understanding of corrosion chemistry (e.g., CRUD formation) has evolved at all scales: micro, meso and macro. CFD R&D has focused on improvement in closure models for subcooled boiling and bubbly flow, and the formulation of robust numerical solution algorithms. For multiphysics integration, several iterative acceleration methods have been assessed, illuminating areas where further research is needed. Finally, uncertainty quantification and data assimilation techniques, based upon sampling approaches, have been made more feasible for practicing nuclear engineers via R&D on dimensional reduction and biased sampling. Industry adoption of CASL's evolving M&S capabilities, which is in progress, will assist in addressing long-standing and future operational and safety challenges of the nuclear industry. - Highlights: • Complexity of physics based modeling of light water reactor cores being addressed. • Capability developed to help address problems that have challenged the nuclear power industry. • Simulation capabilities that take advantage of high performance computing developed.« less

[The dynamic mitochondria-nuclear redistribution of FKBP51 during the process of adipocyte differentiation is regulated by PKA].

PubMed

Toneatto, Judith; Charó, Nancy L; Susperreguy, Sebastián; Piwien-Pilipuk, Graciela

2013-01-01

Glucocorticoids play an important role in adipogenesis via the glucocorticoid receptor (GR) that forms a heterocomplex with Hsp90-Hsp70 and a high molecular weight immunophilin FKBP51 or FKBP52. We have found that FKBP51 level of expression progressively increases, FKBP52 decreases, whereas Hsp90, Hsp70, and p23 remain unchanged when 3T3-L1 preadipocytes differentiate. Interestingly, FKBP51 translocates from mitochondria to the nucleus at the onset of adipogenesis. FKBP51 transiently concentrates in the nuclear lamina, at a time that this nuclear compartment undergoes its reorganization. FKBP51 nuclear localization is transient, after 48 h it cycles back to mitochondria. We found that the dynamic FKBP51 mitochondrial-nuclear shuttling is regulated by glucocorticoids and mainly on cAMP-PKA signaling since PKA inhibition by myristoilated-PKI, abrogated FKBP51 nuclear translocation induced by 3-isobutyl-1-methylxanthine (IBMX). It has been reported that PKA interacts with GR in a ligand dependent manner potentiating its transcriptional capacity. GR transcriptional capacity is reduced when cells are incubated in the presence of IBMX, forskolin or dibutyryl-cAMP, compounds that induced nuclear translocation of FKBP51, therefore PKA may exert a dual role in the control of GR. In summary, the presence of FKBP51 in the nucleus may be critical for GR transcriptional control, and possibly for the control of other transcription factors that are not members of the nuclear receptor family but are regulated by PKA signaling pathway, when transcription has to be strictly controlled to succeed in the acquisition of the adipocyte phenotype.

Divergent mechanisms of insulin-like growth factor I and II on rat hepatocyte proliferation.

PubMed

Raper, S; Kothary, P; Ishoo, E; Dikin, M; Kokudo, N; Hashimoto, M; DeMatteo, R P

1995-07-21

Insulin-like growth factors I and II are peptides with a structural homology for proinsulin, and are involved in hepatocyte proliferation. IGF-I and IGF-II, however, have different metabolic roles, and their mechanisms of action are incompletely known. We hypothesized that IGF-I and IGF-II act by different signal transduction pathways. To test this hypothesis, hepatocytes from 200 g male Sprague-Dawley rats were isolated by a two-step collagenase perfusion technique and plated at a density of 10(5) cells/16 mm Primaria plate. Proliferation was measured by [3H]thymidine ([3H]thy) incorporation into DNA, and an autoradiographic nuclear labeling index (LI). To analyze signal transduction, cyclic AMP (cAMP) levels were measured 5 min after addition of reagents by a radioimmunoassay. Reagents (doses) used were: IGF-I (2 nM), IGF-II (2 nM), the inhibitory peptide somatostatin-14 (SS14) (10 nM), and the adenylyl cyclase antagonist dideoxyadenosine (DDA) (10 microM). A summary of the findings is as follows: (1) IGF-I stimulates [3H]thy, LI and cAMP accumulation. (2) IGF-II stimulates [3H]thy and LI but not cAMP; (3) IGF-I but not IGF-II effects are inhibited by SS14 and DDA. We conclude that the hepatotrophic effects of IGF-I and IGF-II occur by different mechanisms: IGF-I is cAMP-dependent, IGF-II is cAMP-independent.

On the causes of trends in the seasonal amplitude of atmospheric CO2.

PubMed

Piao, Shilong; Liu, Zhuo; Wang, Yilong; Ciais, Philippe; Yao, Yitong; Peng, Shushi; Chevallier, Frédéric; Friedlingstein, Pierre; Janssens, Ivan A; Peñuelas, Josep; Sitch, Stephen; Wang, Tao

2018-02-01

No consensus has yet been reached on the major factors driving the observed increase in the seasonal amplitude of atmospheric CO 2 in the northern latitudes. In this study, we used atmospheric CO 2 records from 26 northern hemisphere stations with a temporal coverage longer than 15 years, and an atmospheric transport model prescribed with net biome productivity (NBP) from an ensemble of nine terrestrial ecosystem models, to attribute change in the seasonal amplitude of atmospheric CO 2 . We found significant (p < .05) increases in seasonal peak-to-trough CO 2 amplitude (AMP P -T ) at nine stations, and in trough-to-peak amplitude (AMP T -P ) at eight stations over the last three decades. Most of the stations that recorded increasing amplitudes are in Arctic and boreal regions (>50°N), consistent with previous observations that the amplitude increased faster at Barrow (Arctic) than at Mauna Loa (subtropics). The multi-model ensemble mean (MMEM) shows that the response of ecosystem carbon cycling to rising CO 2 concentration (eCO 2 ) and climate change are dominant drivers of the increase in AMP P -T and AMP T -P in the high latitudes. At the Barrow station, the observed increase of AMP P -T and AMP T -P over the last 33 years is explained by eCO 2 (39% and 42%) almost equally than by climate change (32% and 35%). The increased carbon losses during the months with a net carbon release in response to eCO 2 are associated with higher ecosystem respiration due to the increase in carbon storage caused by eCO 2 during carbon uptake period. Air-sea CO 2 fluxes (10% for AMP P -T and 11% for AMP T -P ) and the impacts of land-use change (marginally significant 3% for AMP P -T and 4% for AMP T -P ) also contributed to the CO 2 measured at Barrow, highlighting the role of these factors in regulating seasonal changes in the global carbon cycle. © 2017 John Wiley & Sons Ltd.

CTX-M-15 and OXA-10 beta lactamases in multi drug resistant Pseudomonas aeruginosa: First report from Pakistan.

PubMed

Ullah, Waheed; Qasim, Muhammad; Rahman, Hazir; Khan, Saadullah; Rehman, Zia Ur; Ali, Nawab; Muhammad, Noor

2017-04-01

Pseudomonas aeruginosa is an emerging threat to public health worldwide due to their rapid development of drug resistance including beta-lactamases. The present study was designed to investigate the incidence of β-lactamases and genotypic pattern of CTX and OXA in the clinical isolate of multidrug resistant P. aeruginosa. In this study a total of 102 MDR P. aeruginosa isolates obtained from Lady Reading Hospital, Peshawar, Pakistan were subjected to extended spectrum beta lactamase (ESBL), metallo beta lactamase (MBL) and plasmid mediated β-lactamase (AmpC) detection using phenotypic and molecular methods. Furthermore, sequencing of CTX and OXA gene was performed. Out of 102 MDR P. aeruginosa isolates, 71 (69.6%) were beta lactamase producers. The incidence of ESBL, MBL and AmpC in clinical isolates of P. aeruginosa was found to be 23.94%, 40.84% and 35.21% respectively. Co-production of ESBL and AmpC were also observed in some isolates. There were 14 (19.71%) CTX-M-15 harboring isolates which were ESBL (64.28%), MBL (21.42%) and AmpC (14.28%) producer. Co-production of ESBL/MBL (14.28%), ESBL/AmpC (14.28%) and MBL/AmpC (14.28%) were also observed in the CTX M-15 harboring isolates while 12.28% isolates were not ESBL, MBL or AmpC producer. OXA-10 was detected in 8 (11.26%) isolates which were ESBL (12.5%), MBL (37.5%) and AmpC (12.5%) producer. OXA 10 isolates also exhibit co-production of ESBL/AmpC (12.5%) and MBL/AmpC (12.5%). All CTX-M-15 carried the class A β-lactamase conserved domain while OXA-10 harbored conserved domain of class D β-lactamase. The current study for the first time reported and characterized the CTX-M-15 and OXA-10 among MDR P. aeruginosa isolates from Pakistan. Further efforts are needed to understand the molecular mechanism of drug resistance with CTX and OXA harboring P. aeruginosa isolates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Two CGTCA motifs and a GHF1/Pit1 binding site mediate cAMP-dependent protein kinase A regulation of human growth hormone gene expression in rat anterior pituitary GC cells.

PubMed

Shepard, A R; Zhang, W; Eberhardt, N L

1994-01-21

We established the cis-acting elements which mediate cAMP responsiveness of the human growth hormone (hGH) gene in transiently transfected rat anterior pituitary tumor GC cells. Analysis of the intact hGH gene or hGH 5'-flanking DNA (5'-FR) coupled to the hGh cDNA or chloramphenicol acetyltransferase or luciferase genes, indicated that cAMP primarily stimulated hGH promoter activity. Cotransfection of a protein kinase A inhibitory protein cDNA demonstrated that the cAMP response was mediated by protein kinase A. Mutational analysis of the hGH promoter identified two core cAMP response element motifs (CGTCA) located at nucleotides -187/-183 (distal cAMP response element; dCRE) and -99/-95 (proximal cAMP response element; pCRE) and a pituitary-specific transcription factor (GHF1/Pit1) binding site at nucleotides -123/-112 (dGHF1) which were required for cAMP responsiveness. GHF1 was not a limiting factor, since overexpression of GHF1 in cotransfections increased basal but not forskolin induction levels. Gel shift analyses indicated that similar, ubiquitous, thermostable protein(s) specifically bound the pCRE and dCRE motifs. The CGTCA motif-binding factors were cAMP response element binding protein (CREB)/activating transcription factor-1 (ATF-1)-related, since the DNA-protein complex was competed by unlabeled CREB consensus oligonucleotide, specifically supershifted by antisera to CREB and ATF-1 but not ATF-2, and was bound by purified CREB with the same relative binding affinity (pCRE < dCRE < CREB) and mobility as the GC nuclear extract. UV cross-linking and Southwestern blot analyses revealed multiple DNA-protein interactions of which approximately 100- and approximately 45-kDa proteins were predominant; the approximately 45-kDa protein may represent CREB. These results indicate that CREB/ATF-1-related factors act coordinately with the cell-specific factor GHF1 to mediate cAMP-dependent regulation of hGH-1 gene transcription in anterior pituitary somatotrophs.

High-resolution coupled physics solvers for analysing fine-scale nuclear reactor design problems

DOE PAGES

Mahadevan, Vijay S.; Merzari, Elia; Tautges, Timothy; ...

2014-06-30

An integrated multi-physics simulation capability for the design and analysis of current and future nuclear reactor models is being investigated, to tightly couple neutron transport and thermal-hydraulics physics under the SHARP framework. Over several years, high-fidelity, validated mono-physics solvers with proven scalability on petascale architectures have been developed independently. Based on a unified component-based architecture, these existing codes can be coupled with a mesh-data backplane and a flexible coupling-strategy-based driver suite to produce a viable tool for analysts. The goal of the SHARP framework is to perform fully resolved coupled physics analysis of a reactor on heterogeneous geometry, in ordermore » to reduce the overall numerical uncertainty while leveraging available computational resources. Finally, the coupling methodology and software interfaces of the framework are presented, along with verification studies on two representative fast sodium-cooled reactor demonstration problems to prove the usability of the SHARP framework.« less

The Evolution of Soft Collinear Effective Theory

DOE PAGES

Lee, Christopher

2015-02-25

Soft Collinear Effective Theory (SCET) is an effective field theory of Quantum Chromodynamics (QCD) for processes where there are energetic, nearly lightlike degrees of freedom interacting with one another via soft radiation. SCET has found many applications in high-energy and nuclear physics, especially in recent years the physics of hadronic jets in e +e -, lepton-hadron, hadron-hadron, and heavy-ion collisions. SCET can be used to factorize multi-scale cross sections in these processes into single-scale hard, collinear, and soft functions, and to evolve these through the renormalization group to resum large logarithms of ratios of the scales that appear in themore » QCD perturbative expansion, as well as to study properties of nonperturbative effects. We overview the elementary concepts of SCET and describe how they can be applied in high-energy and nuclear physics.« less

An Inexpensive Toroidal Solenoid for an Investigative Student Lab

NASA Astrophysics Data System (ADS)

Ferstl, Andrew; Broberg, John

2008-09-01

Magnetism and Ampère's law is a common subject in most calculus-based introductory physics courses. Many textbooks offer examples to calculate the magnetic field produced by a symmetric current by using Ampère's law. These examples include the solenoid and the toroidal solenoid (sometimes called a torus; see Fig. 1), which are used in many applications, including the study of plasmas.

In vitro modulation of the interaction between HA95 and LAP2beta by cAMP signaling.

PubMed

Martins, Sandra B; Marstad, Anne; Collas, Philippe

2003-09-09

The nuclear envelope mediates key functions by interacting with chromatin. We recently reported an interaction between the chromatin- and nuclear matrix-associated protein HA95 and the inner nuclear membrane integral protein LAP2beta, implicated in initiation of DNA replication (Martins et al. (2003) J. Cell Biol. 160, 177-188). Here, we show that in vitro, interaction between HA95 and LAP2beta is modulated by cAMP signaling via PKA. Exposure of an anti-HA95 immune precipitate from interphase HeLa cells to a mitotic extract promotes ATP-dependent release of LAP2beta from the HA95 complex. This coincides with Ser and Thr phosphorylation of HA95 and LAP2beta. Inhibition of PKA with PKI abolishes phosphorylation of HA95 and dissociation of LAP2beta from HA95, although LAPbeta remains phosphorylated. Antagonizing cAMP signaling in mitotic extract also abolishes the release of LAP2beta from HA95; however, disrupting PKA anchoring to A-kinase anchoring proteins has no effect. Inhibition of CDK activity in the extract greatly reduces LAP2beta phosphorylation but does not prevent LAP2beta release from HA95. Inhibition of PKC, MAP kinase, or CaM kinase II does not affect mitotic extract-induced dissociation of LAP2beta from HA95. PKA phosphorylates HA95 but not LAP2beta in vitro and elicits a release of LAP2beta from HA95. CDK1 or PKC phosphorylates LAP2beta within the HA95 complex, but neither kinase induces LAP2beta release. Our results indicate that in vitro, the interaction between HA95 and LAP2beta is influenced by a PKA-mediated phosphorylation of HA95 rather than by CDK1- or PKC-mediated phosphorylation of LAP2beta. This suggests an additional level of regulation of a chromatin-nuclear envelope interaction in dividing cells.

Expanded spectrum β-lactamase producing Escherichia coli isolated from chickens with colibacillosis in Egypt.

PubMed

El-Shazly, D A; Nasef, S A; Mahmoud, F F; Jonas, Daniel

2017-07-01

Throughout the world, expanded spectrum β-lactamases (ESBL) are increasing among clinical isolates of Enterobacteriaceae, both in humans and animals. Unfortunately, there is a paucity of data on ESBL or Ampicillin class C β-lactamase (AmpC) in Egypt, although antimicrobial consumption is high in this developing country. This study aims to characterize the resistance mechanisms to expanded spectrum cephalosporins among resistant veterinary Escherichia coli isolates in Egypt. We investigated 50 clinical multi-resistant E. coli strains isolated from 20 chicken farms for production of ESBL or AmpC. Antibiotic susceptibility was tested by Clinical and Laboratory Standards Institute (CLSI) disk diffusion and ESBL confirmatory tests. PCR and sequencing were performed to screen for plasmid mediated ESBL genes and genes encoding AmpC β-lactamases. All the isolates were phylogentically classified, investigated for harboring class 1 integrons, and genotyped by amplified fragment length polymorphism (AFLP). Three strains showed ESBL and 6 strains AmpC phenotypic patterns, respectively, with confirmed ESBL genes of blaTEM-57, blaSHV-12, blaCTX-M-14, and blaCMY-2 for AmpC producing strains. All ESBL strains belonged to phylogroup D with different clones isolated from different flocks, while most of the AmpC strains belonged to phylogroup B1 (4/6) and were assigned to the same genotype distributed in 2 different farms. Class 1 integrons were disseminated in 60% of all tested strains and in 100% of ESBL and AmpC strains. These results highlight the antimicrobial resistance problem in Egypt, caused in all probability by unwise use of antimicrobials in animal husbandry. The results call for a nationwide surveillance program to monitor antimicrobial resistance. © 2017 Poultry Science Association Inc.

The quaternary architecture of RARβ–RXRα heterodimer facilitates domain–domain signal transmission

DOE PAGES

Chandra, Vikas; Wu, Dalei; Li, Sheng; ...

2017-10-11

Assessing the physical connections and allosteric communications in multi-domain nuclear receptor (NR) polypeptides has remained challenging, with few crystal structures available to show their overall structural organizations. Here we report the quaternary architecture of multi-domain retinoic acid receptor beta-retinoic X receptor alpha (RAR beta-RXR alpha) heterodimer bound to DNA, ligands and coactivator peptides, examined through crystallographic, hydrogen-deuterium exchange mass spectrometry, mutagenesis and functional studies. The RAR beta ligand-binding domain (LBD) and DNA-binding domain (DBD) are physically connected to foster allosteric signal transmission between them. Direct comparisons among all the multi-domain NRs studied crystallographically to date show significant variations within theirmore » quaternary architectures, rather than a common architecture adhering to strict rules. RXR remains flexible and adaptive by maintaining loosely organized domains, while its hetero-dimerization partners use a surface patch on their LBDs to form domain-domain interactions with DBDs.« less

The quaternary architecture of RARβ–RXRα heterodimer facilitates domain–domain signal transmission

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

Chandra, Vikas; Wu, Dalei; Li, Sheng

Assessing the physical connections and allosteric communications in multi-domain nuclear receptor (NR) polypeptides has remained challenging, with few crystal structures available to show their overall structural organizations. Here we report the quaternary architecture of multi-domain retinoic acid receptor beta-retinoic X receptor alpha (RAR beta-RXR alpha) heterodimer bound to DNA, ligands and coactivator peptides, examined through crystallographic, hydrogen-deuterium exchange mass spectrometry, mutagenesis and functional studies. The RAR beta ligand-binding domain (LBD) and DNA-binding domain (DBD) are physically connected to foster allosteric signal transmission between them. Direct comparisons among all the multi-domain NRs studied crystallographically to date show significant variations within theirmore » quaternary architectures, rather than a common architecture adhering to strict rules. RXR remains flexible and adaptive by maintaining loosely organized domains, while its hetero-dimerization partners use a surface patch on their LBDs to form domain-domain interactions with DBDs.« less

Nuclear analytical techniques in medicine

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

Cesareo, R.

1988-01-01

This book acquaints one with the fundamental principles and the instrumentation relevant to analytical technique based on atomic and nuclear physics, as well as present and future biomedical applications. Besides providing a theoretical description of the physical phenomena, a large part of the book is devoted to applications in the medical and biological field, particularly in hematology, forensic medicine and environmental science. This volume reviews methods such as the possibility of carrying out rapid multi-element analysis of trace elements on biomedical samples, in vitro and in vivo, by XRF-analysis; the ability of the PIXE-microprobe to analyze in detail and tomore » map trace elements in fragments of biomedical samples or inside the cells; the potentiality of in vivo nuclear activation analysis for diagnostic purposes. Finally, techniques are described such as radiation scattering (elastic and inelastic scattering) and attenuation measurements which will undoubtedly see great development in the immediate future.« less

Publications - GMC 70 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS GMC 70 Publication Details Title: Core permeability determinations and other related physical determinations and other related physical analyses of 20 North Slope wells: Alaska Division of Geological &

High-density antimicrobial peptide coating with broad activity and low cytotoxicity against human cells.

PubMed

Rai, Akhilesh; Pinto, Sandra; Evangelista, Marta B; Gil, Helena; Kallip, Silvar; Ferreira, Mario G S; Ferreira, Lino

2016-03-01

Medical device-associated infections are a multi-billion dollar burden for the worldwide healthcare systems. The modification of medical devices with non-leaching coatings capable of killing microorganisms on contact is one of the strategies being investigated to prevent microorganism colonization. Here we developed a robust antimicrobial coating based on the chemical immobilization of the antimicrobial peptide (AMP), cecropin-melittin (CM), on gold nanoparticles coated surfaces. The concentration of AMP immobilized (110 μg/cm(2)) was higher than most of the studies reported so far (<10 μg/cm(2)). This translated onto a coating with high antimicrobial activity against Gram positive and negative bacteria sp., as well as multi-drug resistant bacteria. Studies with E. coli reporter bacteria showed that these coatings induced the permeability of the outer membrane of bacteria in less than 5 min and the inner membrane in approximately 20 min. Importantly, the antimicrobial properties of the coating are maintained in the presence of 20% (v/v) human serum, and have low probability to induce bacteria resistance. We further show that coatings have low toxicity against human endothelial and fibroblast cells and is hemocompatible since it does not induce platelet and complement activation. The antimicrobial coating described here may be promising to prevent medical device-associated infections. In recent years, antimicrobial peptides (AMPs) have been chemically immobilized on surfaces of medical devices to render them with antimicrobial properties. Surfaces having immobilized cationic peptides are susceptible to be adsorbed by plasma proteins with the subsequent loss of antimicrobial activity. Furthermore, with the exception of very few studies that have determined the cytotoxicity of surfaces in mammalian cells, the effect of the immobilized AMP on human cells is relatively unknown. Here we report a coating based on cecropin-melittin peptide (CM) that maintains its antimicrobial activity against Gram-positive and negative bacteria including multi-drugs resistance bacteria in the presence of serum and has relatively low cytotoxicity against human cells. The reported coatings may be translated on to variety of substrates (glass and titanium) and medical devices to prevent device-associated microbial infection. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Advancing the adverse outcome pathway framework: An international horizon scanning approach

EPA Science Inventory

In 2016, an international multi-sector steering committee focusing on the development of a Society of Environmental Toxicology & Chemistry (SETAC) Pellston™ Workshop reached out to the membership of the Society of Toxicology, as well as other national and internatio...

Identification of the cAMP response element that controls transcriptional activation of the insulin-like growth factor-I gene by prostaglandin E2 in osteoblasts

NASA Technical Reports Server (NTRS)

Thomas, M. J.; Umayahara, Y.; Shu, H.; Centrella, M.; Rotwein, P.; McCarthy, T. L.

1996-01-01

Insulin-like growth factor-I (IGF-I), a multifunctional growth factor, plays a key role in skeletal growth and can enhance bone cell replication and differentiation. We previously showed that prostaglandin E2 (PGE2) and other agents that increase cAMP activated IGF-I gene transcription in primary rat osteoblast cultures through promoter 1 (P1), the major IGF-I promoter, and found that transcriptional induction was mediated by protein kinase A. We now have identified a short segment of P1 that is essential for full hormonal regulation and have characterized inducible DNA-protein interactions involving this site. Transient transfections of IGF-I P1 reporter genes into primary rat osteoblasts showed that the 328-base pair untranslated region of exon 1 was required for a full 5.3-fold response to PGE2; mutation in a previously footprinted site, HS3D (base pairs +193 to +215), reduced induction by 65%. PGE2 stimulated nuclear protein binding to HS3D. Binding, as determined by gel mobility shift assay, was not seen in nuclear extracts from untreated osteoblast cultures, was detected within 2 h of PGE2 treatment, and was maximal by 4 h. This DNA-protein interaction was not observed in cytoplasmic extracts from PGE2-treated cultures, indicating nuclear localization of the protein kinase A-activated factor(s). Activation of this factor was not blocked by cycloheximide (Chx), and Chx did not impair stimulation of IGF-I gene expression by PGE2. In contrast, binding to a consensus cAMP response element (CRE; 5'-TGACGTCA-3') from the rat somatostatin gene was not modulated by PGE2 or Chx. Competition gel mobility shift analysis using mutated DNA probes identified 5'-CGCAATCG-3' as the minimal sequence needed for inducible binding. All modified IGF-I P1 promoterreporter genes with mutations within this CRE sequence also showed a diminished functional response to PGE2. These results identify the CRE within the 5'-untranslated region of IGF-I exon 1 that is required for hormonal activation of IGF-I gene transcription by cAMP in osteoblasts.

Hybrid Dion-Jacobson 2D Lead Iodide Perovskites.

PubMed

Mao, Lingling; Ke, Weijun; Pedesseau, Laurent; Wu, Yilei; Katan, Claudine; Even, Jacky; Wasielewski, Michael R; Stoumpos, Constantinos C; Kanatzidis, Mercouri G

2018-03-14

The three-dimensional hybrid organic-inorganic perovskites have shown huge potential for use in solar cells and other optoelectronic devices. Although these materials are under intense investigation, derivative materials with lower dimensionality are emerging, offering higher tunability of physical properties and new capabilities. Here, we present two new series of hybrid two-dimensional (2D) perovskites that adopt the Dion-Jacobson (DJ) structure type, which are the first complete homologous series reported in halide perovskite chemistry. Lead iodide DJ perovskites adopt a general formula A'A n-1 Pb n I 3 n+1 (A' = 3-(aminomethyl)piperidinium (3AMP) or 4-(aminomethyl)piperidinium (4AMP), A = methylammonium (MA)). These materials have layered structures where the stacking of inorganic layers is unique as they lay exactly on top of another. With a slightly different position of the functional group in the templating cation 3AMP and 4AMP, the as-formed DJ perovskites show different optical properties, with the 3AMP series having smaller band gaps than the 4AMP series. Analysis on the crystal structures and density functional theory (DFT) calculations suggest that the origin of the systematic band gap shift is the strong but indirect influence of the organic cation on the inorganic framework. Fabrication of photovoltaic devices utilizing these materials as light absorbers reveals that (3AMP)(MA) 3 Pb 4 I 13 has the best power conversion efficiency (PCE) of 7.32%, which is much higher than that of the corresponding (4AMP)(MA) 3 Pb 4 I 13 .

Cilostamide and forskolin treatment during pre-IVM improves preimplantation development of cloned embryos by influencing meiotic progression and gap junction communication in pigs.

PubMed

Park, Bola; Lee, Hanna; Lee, Yongjin; Elahi, Fazle; Lee, Joohyeong; Lee, Seung Tae; Park, Choon-Keun; Hyun, Sang-Hwan; Lee, Eunsong

2016-08-01

This study was conducted to evaluate the effects of treatment with the cAMP modulators cilostamide and/or forskolin during pre-IVM culture on meiotic progression, gap junction communication, intraoocyte cAMP level and glutathione content, embryonic development after parthenogenesis, and somatic cell nuclear transfer in pigs. Cumulus-oocyte complexes were cultured for 24 hours in unsupplemented medium or media containing 20 μM cilostamide and/or 50 μM forskolin. After pre-IVM, oocytes were cultured for 41 to 44 hours in a standard IVM medium to induce oocyte maturation. When the nuclear status of oocytes was examined after pre-IVM for 24 hours, a higher (P < 0.01) proportion of oocytes treated with forskolin (85.5%) and cilostamide + forskolin (92.6%) remained at the germinal vesicle stage compared with untreated (20.6%) and cilostamide-treated oocytes (54.7%). cAMP level in pre-IVM oocytes was significantly increased by combined treatment with cilostamide + forskolin (21.38 fmol/oocyte) relative to the no pre-IVM control, no treatment, cilostamide, and forskolin groups (2.85, 1.88, 1.74, and 8.95 fmol/oocyte, respectively). Forskolin with or without cilostamide significantly maintained open-gap junction communication relative to no treatment. Blastocyst formation in parthenogenesis was significantly (P < 0.01) improved by forskolin (65.3%) relative to other treatments (28.3% to 48.1%). Supplementation of pre-IVM with dibutyryl cAMP showed similar blastocyst formation as forskolin treatment (61.1% and 61.0%, respectively). In somatic cell nuclear transfer, simultaneous treatment with cilostamide + forskolin significantly (P < 0.05) increased embryonic development to the blastocyst stage (42.9%) relative to the no pre-IVM, control, and cilostamide groups (32.3, 28.6, and 32.8%, respectively). The glutathione contents in pre-IVM oocytes were increased by no treatment, forskolin, and cilostamide + forskolin (1.38, 1.39, and 1.27 pixels/oocyte, respectively) compared with no pre-IVM and cilostamide (1.00 and 0.99 pixels/oocyte, respectively; P < 0.05). Our results reported that the meiotic progression of immature pig oocytes could be reversibly attenuated by cAMP, whereas treatment with cilostamide and forskolin during pre-IVM had positive effects on developmental competence of oocytes in pigs, probably by improving cytoplasmic maturation. Copyright © 2016 Elsevier Inc. All rights reserved.

Antimicrobial combinations: Bliss independence and Loewe additivity derived from mechanistic multi-hit models

PubMed Central

Yu, Guozhi; Hozé, Nathanaël; Rolff, Jens

2016-01-01

Antimicrobial peptides (AMPs) and antibiotics reduce the net growth rate of bacterial populations they target. It is relevant to understand if effects of multiple antimicrobials are synergistic or antagonistic, in particular for AMP responses, because naturally occurring responses involve multiple AMPs. There are several competing proposals describing how multiple types of antimicrobials add up when applied in combination, such as Loewe additivity or Bliss independence. These additivity terms are defined ad hoc from abstract principles explaining the supposed interaction between the antimicrobials. Here, we link these ad hoc combination terms to a mathematical model that represents the dynamics of antimicrobial molecules hitting targets on bacterial cells. In this multi-hit model, bacteria are killed when a certain number of targets are hit by antimicrobials. Using this bottom-up approach reveals that Bliss independence should be the model of choice if no interaction between antimicrobial molecules is expected. Loewe additivity, on the other hand, describes scenarios in which antimicrobials affect the same components of the cell, i.e. are not acting independently. While our approach idealizes the dynamics of antimicrobials, it provides a conceptual underpinning of the additivity terms. The choice of the additivity term is essential to determine synergy or antagonism of antimicrobials. This article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’. PMID:27160596

Protective features of resveratrol on human spermatozoa cryopreservation may be mediated through 5' AMP-activated protein kinase activation.

PubMed

Shabani Nashtaei, M; Amidi, F; Sedighi Gilani, M A; Aleyasin, A; Bakhshalizadeh, Sh; Naji, M; Nekoonam, S

2017-03-01

Biochemical and physical modifications during the freeze-thaw process adversely influence the restoration of energy-dependent sperm functions required for fertilization. Resveratrol, a phytoalexin, has been introduced to activate 5' AMP-activated protein kinase which is a cell energy sensor and a cell metabolism regulator. The cryoprotection of resveratrol on sperm cryoinjury via activation of AMP-activated protein kinase also remains to be elucidated. Our aim, thus, was to investigate: (i) the presence and intracellular localization of AMP-activated protein kinase protein; (ii) whether resveratrol may exert a protective effect on certain functional properties of fresh and post-thaw human spermatozoa through modulation of AMP-activated protein kinase. Spermatozoa from normozoospermic men were incubated with or without different concentrations of Compound C as an AMP-activated protein kinase inhibitor or resveratrol as an AMP-activated protein kinase activator for different lengths of time and were then cryopreserved. AMP-activated protein kinase is expressed essentially in the entire flagellum and the post-equatorial region. Viability of fresh spermatozoa was not significantly affected by the presence of Compound C or resveratrol. However, although Compound C caused a potent inhibition of spermatozoa motility parameters, resveratrol did not induce negative effect, except a significant reduction in motility at 25 μm for 1 h. Furthermore, resveratrol significantly increased AMP-activated protein kinase phosphorylation and mitochondrial membrane potential and decreased reactive oxygen species and apoptosis-like changes in frozen-thawed spermatozoa. Nevertheless, it was not able to compensate decreased sperm viability and motility parameters following cryopreservation. In contrast, Compound C showed opposite effects to resveratrol on AMP-activated protein kinase phosphorylation, reactive oxygen species, apoptosis-like changes, mitochondrial membrane potential, and motility parameters. These findings, although preliminary, suggest that resveratrol-induced improvement of cryopreserved sperm functions may be mediated through activation of AMP-activated protein kinase, indicating the importance of AMP-activated protein kinase activity for human spermatozoa functions. Further investigations are required to elucidate the mechanism by which resveratrol ameliorates oxidative stress-mediated damages in an AMP-activated protein kinase-dependent mechanism. © 2016 American Society of Andrology and European Academy of Andrology.

8-CPT-cAMP/all-trans retinoic acid targets t(11;17) acute promyelocytic leukemia through enhanced cell differentiation and PLZF/RARα degradation

PubMed Central

Jiao, Bo; Ren, Zhi-Hong; Liu, Ping; Chen, Li-Juan; Shi, Jing-Yi; Dong, Ying; Ablain, Julien; Shi, Lin; Gao, Li; Hu, Jun-Pei; Ren, Rui-Bao; de Thé, Hugues; Chen, Zhu; Chen, Sai-Juan

2013-01-01

The refractoriness of acute promyelocytic leukemia (APL) with t(11;17)(q23;q21) to all-trans retinoic acid (ATRA)-based therapy concerns clinicians and intrigues basic researchers. By using a murine leukemic model carrying both promyelocytic leukemia zinc finger/retinoic acid receptor-α (PLZF/RARα) and RARα/PLZF fusion genes, we discovered that 8-chlorophenylthio adenosine-3′, 5′-cyclic monophosphate (8-CPT-cAMP) enhances cellular differentiation and improves gene trans-activation by ATRA in leukemic blasts. Mechanistically, in combination with ATRA, 8-CPT-cAMP activates PKA, causing phosphorylation of PLZF/RARα at Ser765 and resulting in increased dissociation of the silencing mediator for retinoic acid and thyroid hormone receptors/nuclear receptor corepressor from PLZF/RARα. This process results in changes of local chromatin and transcriptional reactivation of the retinoic acid pathway in leukemic cells. Meanwhile, 8-CPT-cAMP also potentiated ATRA-induced degradation of PLZF/RARα through its Ser765 phosphorylation. In vivo treatment of the t(11;17) APL mouse model demonstrated that 8-CPT-cAMP could significantly improve the therapeutic effect of ATRA by targeting a leukemia-initiating cell activity. This combined therapy, which induces enhanced differentiation and oncoprotein degradation, may benefit t(11;17) APL patients. PMID:23382200

Inhibition of src family kinases by a combinatorial action of 5'-AMP and small heat shock proteins, identified from the adult heart.

PubMed

Kasi, V S; Kuppuswamy, D

1999-10-01

Src family kinases are implicated in cellular proliferation and transformation. Terminally differentiated myocytes have lost the ability to proliferate, indicating the existence of a down-regulatory mechanism(s) for these mitogenic kinases. Here we show that feline cardiomyocyte lysate contains thermostable components that inhibit c-Src kinase in vitro. This inhibitory activity, present predominantly in heart tissue, involves two components acting combinatorially. After purification by sequential chromatography, one component was identified by mass and nuclear magnetic resonance spectroscopies as 5'-AMP, while the other was identified by peptide sequencing as a small heat shock protein (sHSP). 5'-AMP and to a lesser extent 5'-ADP inhibit c-Src when combined with either HSP-27 or HSP-32. Other HSPs, including alphaB-crystallin, HSP-70, and HSP-90, did not exhibit this effect. The inhibition, observed preferentially on Src family kinases and independent of the Src tyrosine phosphorylation state, occurs via a direct interaction of the c-Src catalytic domain with the inhibitory components. Our study indicates that sHSPs increase the affinity of 5'-AMP for the c-Src ATP binding site, thereby facilitating the inhibition. In vivo, elevation of ATP levels in the cardiomyocytes results in the tyrosine phosphorylation of cellular proteins including c-Src at the activatory site, and this effect is blocked when the 5'-AMP concentration is raised. Thus, this study reveals a novel role for sHSPs and 5'-AMP in the regulation of Src family kinases, presumably for the maintenance of the terminally differentiated state.

Nb3Sn SRF Cavities for Nuclear Physics Applications

NASA Astrophysics Data System (ADS)

Eremeev, Grigory

2017-01-01

Nuclear physics experiments rely increasingly on accelerators, which employ superconducting RF (SRF) technology. CEBAF, SNS, FRIB, ESS, among others exploit the low surface resistance of SRF cavities to efficiently accelerate particle beams towards experimental targets. Niobium is the cavity material of choice for all current or planned SRF accelerators, but it has been long recognized that other superconductors with high superconducting transition temperatures have the potential to surpass niobium for SRF applications. Among the alternatives, Nb3Sn coated cavities are the most advanced on the path to practical applications: Nb3Sn coatings on R&D cavities have Tc consistently close the optimal 18 K, very low RF surface resistances, and very recently were shown to reach above Hc1 without anomalous RF surface resistance increase. In my talk I will discuss the prospects of Nb3Sn SRF cavities, the research efforts to realize Nb3Sn coatings on practical multi-cell accelerating structures, and the path toward possible inclusion in CEBAF. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics.

AMP-activated protein kinase is involved in the activation of the Fanconi anemia/BRCA pathway in response to DNA interstrand crosslinks.

PubMed

Chun, Min Jeong; Kim, Sunshin; Hwang, Soo Kyung; Kim, Bong Sub; Kim, Hyoun Geun; Choi, Hae In; Kim, Jong Heon; Goh, Sung Ho; Lee, Chang-Hun

2016-08-16

Fanconi anemia complementation group (FANC) proteins constitute the Fanconi Anemia (FA)/BRCA pathway that is activated in response to DNA interstrand crosslinks (ICLs). We previously performed yeast two-hybrid screening to identify novel FANC-interacting proteins and discovered that the alpha subunit of AMP-activated protein kinase (AMPKα1) was a candidate binding partner of the FANCG protein, which is a component of the FA nuclear core complex. We confirmed the interaction between AMPKα and both FANCG using co-immunoprecipitation experiments. Additionally, we showed that AMPKα interacted with FANCA, another component of the FA nuclear core complex. AMPKα knockdown in U2OS cells decreased FANCD2 monoubiquitination and nuclear foci formation upon mitomycin C-induced ICLs. Furthermore, AMPKα knockdown enhanced cellular sensitivity to MMC. MMC treatment resulted in an increase in AMPKα phosphorylation/activation, indicating AMPK is involved in the cellular response to ICLs. FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway. Our data suggest AMPK is involved in the activation of the FA/BRCA pathway.

Comparison of the overlapping frd and ampC operons of Escherichia coli with the corresponding DNA sequences in other gram-negative bacteria.

PubMed

Bergström, S; Lindberg, F P; Olsson, O; Normark, S

1983-09-01

Specific DNA probes from Escherichia coli K-12 were used to analyze the sequence divergence of the frd and ampC operons in various species of gram-negative bacteria. These operons code for the fumarate reductase complex and the chromosomal beta-lactamase, respectively. We demonstrate that the two operons show the same general pattern of divergence, although the frd operon is considerably more conserved than is the ampC operon. The major exception is Salmonella typhimurium LT2, which shows a strong homology to the E. coli frd probe but none to the E. coli ampC probe. The operons from Citrobacter freundii and Shigella sonnei were cloned and characterized by physical mapping, Southern hybridization, and protein synthesis in minicells. In S. sonnei, as in E. coli K-12, the frd and ampC operons overlap (T. Grundström and B. Jaurin, Proc. Natl. Acad. Sci. U.S.A. 79:1111-1115, 1982). Only minor discrepancies between the two operons were found over the entire frd-ampC region. In C. freundii, the ampC and frd operons do not overlap, being separated by about 1,100 base pairs. Presumably the inducible property of the C. freundii chromosomal beta-lactamase is encoded by this 1,100-base-pair DNA segment.

Epidemiology of Extended-Spectrum β-Lactamase-Producing E. coli and Vancomycin-Resistant Enterococci in the Northern Dutch-German Cross-Border Region.

PubMed

Zhou, Xuewei; García-Cobos, Silvia; Ruijs, Gijs J H M; Kampinga, Greetje A; Arends, Jan P; Borst, Dirk M; Möller, Lieke V; Holman, Nicole D; Schuurs, Theo A; Bruijnesteijn van Coppenraet, Lesla E; Weel, Jan F; van Zeijl, Jan H; Köck, Robin; Rossen, John W A; Friedrich, Alexander W

2017-01-01

Objectives: To reveal the prevalence and epidemiology of extended-spectrum β-lactamase (ESBL)- and/or plasmid AmpC (pAmpC)- and carbapenemase (CP) producing Enterobacteriaceae and vancomycin-resistant enterococci (VRE) across the Northern Dutch-German border region. Methods: A point-prevalence study on ESBL/pAmpC/CP producing Enterobacteriaceae and VRE was carried out in hospitalized patients in the Northern Netherlands ( n = 445, 2012-2013) and Germany ( n = 242, 2012). Healthy individuals from the Dutch community ( n = 400, 2010-2012) were also screened. In addition, a genome-wide gene-by-gene approach was applied to study the epidemiology of ESBL- Escherichia coli and VRE. Results: A total of 34 isolates from 27 patients (6.1%) admitted to Dutch hospitals were ESBL/pAmpC positive and 29 ESBL- E. coli , three pAmpC- E. coli , one ESBL- Enterobacter cloacae , and one pAmpC- Proteus mirabilis were found. In the German hospital, 18 isolates (16 E. coli and 2 Klebsiella pneumoniae ) from 17 patients (7.7%) were ESBL positive. In isolates from the hospitalized patients CTX-M-15 was the most frequently detected ESBL-gene. In the Dutch community, 11 individuals (2.75%) were ESBL/pAmpC positive: 10 ESBL - E. coli (CTX-M-1 being the most prevalent gene) and one pAmpC E. coli . Six Dutch (1.3%) and four German (3.9%) hospitalized patients were colonized with VRE. Genetic relatedness by core genome multi-locus sequence typing (cgMLST) was found between two ESBL- E. coli isolates from Dutch and German cross-border hospitals and between VRE isolates from different hospitals within the same region. Conclusion: The prevalence of ESBL/pAmpC- Enterobacteriaceae was similar in hospitalized patients across the Dutch-German border region, whereas VRE prevalence was slightly higher on the German side. The overall prevalence of the studied pathogens was lower in the community than in hospitals in the Northern Netherlands. Cross-border transmission of ESBL- E. coli and VRE seems unlikely based on cgMLST analysis, however continuous monitoring is necessary to control their spread and stay informed about their epidemiology.

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

McNally, J.J.

The effects on the properties of Ta/sub 2/O/sub 5/, Al/sub 2/O/sub 3/, SiO/sub 2/ and HfO/sub 2/ single- and multi-layer optical coatings deposited using ion-assisted deposition (IAD) were investigated. IAD is a novel deposition technique which utilizes a separate ion source to direct a beam of ions at the growing film. A Kaufman ion source was used to provide a monoenergetic, neutralized beam of oxygen ions independent of the material evaporation process. The optical and physical properties, as well as laser induced damage threshold (LIDT) values, were studied for coatings bombarded with 200, 300, 500 and 1000 eV oxygen ionsmore » at values of current density from 0 to 200 microAmp/sq cm. IAD was successfully applied to deposit coatings at low temperature on heavy metal fluoride (HMF) glass substrates. The coatings deposited using IAD were hard and dense. The IAD coatings improved the durability and abrasion resistance of the HMF glass substrates. The results of this investigation show that IAD can be used to improve the optical and physical properties of optical coatings.« less

40 CFR 180.1149 - Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Inclusion bodies of the multi-nuclear... Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from the requirement of a tolerance. The microbial pest control agent inclusion bodies of the multi-nuclear...

High Heterogeneity of Escherichia coli Sequence Types Harbouring ESBL/AmpC Genes on IncI1 Plasmids in the Colombian Poultry Chain

PubMed Central

Donado-Godoy, Pilar; León, Maribel; Clavijo, Viviana; Arevalo, Alejandra; Bernal, Johan F.; Timmerman, Arjen J.; Mevius, Dik J.; Wagenaar, Jaap A.; Hordijk, Joost

2017-01-01

Background Escherichia coli producing ESBL/AmpC enzymes are unwanted in animal production chains as they may pose a risk to human and animal health. Molecular characterization of plasmids and strains carrying genes that encode these enzymes is essential to understand their local and global spread. Objectives To investigate the diversity of genes, plasmids and strains in ESBL/AmpC-producing E. coli from the Colombian poultry chain isolated within the Colombian Integrated Program for Antimicrobial Resistance Surveillance (Coipars). Methods A total of 541 non-clinical E. coli strains from epidemiologically independent samples and randomly isolated between 2008 and 2013 within the Coipars program were tested for antimicrobial susceptibility. Poultry isolates resistant to cefotaxime (MIC ≥ 4 mg/L) were screened for ESBL/AmpC genes including blaCTX-M, blaSHV, blaTEM, blaCMY and blaOXA. Plasmid and strain characterization was performed for a selection of the ESBL/AmpC-producing isolates. Plasmids were purified and transformed into E. coli DH10B cells or transferred by conjugation to E. coli W3110. When applicable, PCR Based Replicon Typing (PBRT), plasmid Multi Locus Sequence Typing (pMLST), plasmid Double Locus Sequence Typing (pDLST) and/or plasmid Replicon Sequence Typing (pRST) was performed on resulting transformants and conjugants. Multi Locus Sequence Typing (MLST) was used for strain characterization. Results In total, 132 of 541 isolates were resistant to cefotaxime and 122 were found to carry ESBL/AmpC genes. Ninety-two harboured blaCMY-2 (75%), fourteen blaSHV-12 (11%), three blaSHV-5 (2%), five blaCTX-M-2 (4%), one blaCTX-M-15 (1%), one blaCTX-M-8 (1%), four a combination of blaCMY-2 and blaSHV-12 (4%) and two a combination of blaCMY-2 and blaSHV-5 (2%). A selection of 39 ESBL/AmpC-producing isolates was characterized at the plasmid and strain level. ESBL/AmpC genes from 36 isolates were transferable by transformation or conjugation of which 22 were located on IncI1 plasmids. These IncI1 plasmids harboured predominantly blaCMY-2 (16/22), and to a lesser extend blaSHV-12 (5/22) and blaCTX-M-8 (1/22). Other plasmid families associated with ESBL/AmpC-genes were IncK (4/33), IncHI2 (3/33), IncA/C (2/33), IncΒ/O (1/33) and a non-typeable replicon (1/33). Subtyping of IncI1 and IncHI2 demonstrated IncI1/ST12 was predominantly associated with blaCMY-2 (12/16) and IncHI2/ST7 with blaCTX-M-2 (2/3). Finally, 31 different STs were detected among the 39 selected isolates. Conclusions Resistance to extended spectrum cephalosporins in E. coli from Colombian poultry is mainly caused by blaCMY-2 and blaSHV-12. The high diversity of strain Sequence Types and the dissemination of homogeneous IncI1/ST12 plasmids suggest that spread of the resistance is mainly mediated by horizontal gene transfer. PMID:28125687

High Heterogeneity of Escherichia coli Sequence Types Harbouring ESBL/AmpC Genes on IncI1 Plasmids in the Colombian Poultry Chain.

PubMed

Castellanos, Luis Ricardo; Donado-Godoy, Pilar; León, Maribel; Clavijo, Viviana; Arevalo, Alejandra; Bernal, Johan F; Timmerman, Arjen J; Mevius, Dik J; Wagenaar, Jaap A; Hordijk, Joost

2017-01-01

Escherichia coli producing ESBL/AmpC enzymes are unwanted in animal production chains as they may pose a risk to human and animal health. Molecular characterization of plasmids and strains carrying genes that encode these enzymes is essential to understand their local and global spread. To investigate the diversity of genes, plasmids and strains in ESBL/AmpC-producing E. coli from the Colombian poultry chain isolated within the Colombian Integrated Program for Antimicrobial Resistance Surveillance (Coipars). A total of 541 non-clinical E. coli strains from epidemiologically independent samples and randomly isolated between 2008 and 2013 within the Coipars program were tested for antimicrobial susceptibility. Poultry isolates resistant to cefotaxime (MIC ≥ 4 mg/L) were screened for ESBL/AmpC genes including blaCTX-M, blaSHV, blaTEM, blaCMY and blaOXA. Plasmid and strain characterization was performed for a selection of the ESBL/AmpC-producing isolates. Plasmids were purified and transformed into E. coli DH10B cells or transferred by conjugation to E. coli W3110. When applicable, PCR Based Replicon Typing (PBRT), plasmid Multi Locus Sequence Typing (pMLST), plasmid Double Locus Sequence Typing (pDLST) and/or plasmid Replicon Sequence Typing (pRST) was performed on resulting transformants and conjugants. Multi Locus Sequence Typing (MLST) was used for strain characterization. In total, 132 of 541 isolates were resistant to cefotaxime and 122 were found to carry ESBL/AmpC genes. Ninety-two harboured blaCMY-2 (75%), fourteen blaSHV-12 (11%), three blaSHV-5 (2%), five blaCTX-M-2 (4%), one blaCTX-M-15 (1%), one blaCTX-M-8 (1%), four a combination of blaCMY-2 and blaSHV-12 (4%) and two a combination of blaCMY-2 and blaSHV-5 (2%). A selection of 39 ESBL/AmpC-producing isolates was characterized at the plasmid and strain level. ESBL/AmpC genes from 36 isolates were transferable by transformation or conjugation of which 22 were located on IncI1 plasmids. These IncI1 plasmids harboured predominantly blaCMY-2 (16/22), and to a lesser extend blaSHV-12 (5/22) and blaCTX-M-8 (1/22). Other plasmid families associated with ESBL/AmpC-genes were IncK (4/33), IncHI2 (3/33), IncA/C (2/33), IncΒ/O (1/33) and a non-typeable replicon (1/33). Subtyping of IncI1 and IncHI2 demonstrated IncI1/ST12 was predominantly associated with blaCMY-2 (12/16) and IncHI2/ST7 with blaCTX-M-2 (2/3). Finally, 31 different STs were detected among the 39 selected isolates. Resistance to extended spectrum cephalosporins in E. coli from Colombian poultry is mainly caused by blaCMY-2 and blaSHV-12. The high diversity of strain Sequence Types and the dissemination of homogeneous IncI1/ST12 plasmids suggest that spread of the resistance is mainly mediated by horizontal gene transfer.

Phosphorylated nitrate reductase and 14-3-3 proteins. Site of interaction, effects of ions, and evidence for an amp-binding site on 14-3-3 proteins.

PubMed

Athwal, G S; Huber, J L; Huber, S C

1998-11-01

The inactivation of phosphorylated nitrate reductase (NR) by the binding of 14-3-3 proteins is one of a very few unambiguous biological functions for 14-3-3 proteins. We report here that serine and threonine residues at the +6 to +8 positions, relative to the known regulatory binding site involving serine-543, are important in the interaction with GF14omega, a recombinant plant 14-3-3. Also shown is that an increase in ionic strength with KCl or inorganic phosphate, known physical effectors of NR activity, directly disrupts the binding of protein and peptide ligands to 14-3-3 proteins. Increased ionic strength attributable to KCl caused a change in conformation of GF14omega, resulting in reduced surface hydrophobicity, as visualized with a fluorescent probe. Similarly, it is shown that the 5' isomer of AMP was specifically able to disrupt the inactive phosphorylated NR:14-3-3 complex. Using the 5'-AMP fluorescent analog trinitrophenyl-AMP, we show that there is a probable AMP-binding site on GF14omega.

77 FR 41457 - Aging Management Associated With Wall Thinning Due to Erosion Mechanisms

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0170] Aging Management Associated With Wall Thinning Due... management program (AMP) in NUREG-1801, Revision 2, ``Generic Aging Lessons Learned (GALL) Report,'' and the NRC staff's aging management review procedure and acceptance criteria contained in NUREG-1800...

Present status of the KISS project

NASA Astrophysics Data System (ADS)

Miyatake, H.; Wada, M.; Watanabe, X. Y.; Hirayama, Y.; Schury, P.; Ahmed, M.; Ishiyama, H.; Jeong, S. C.; Kakiguchi, Y.; Kimura, S.; Moon, J. Y.; Mukai, M.; Oyaizu, M.; Park, J. H.

2018-04-01

KISS project aims at finding an astrophysical condition for synthesizing r-process heavy element isotopes, which are characterized as the third peak in the solar abundance pattern. This is an experimental challenge in nuclear physics to measure ground and isomeric state properties of unknown nuclei around the region of N=126 isotones. So far we have constructed and developed new type of mass separation system, KISS (KEK Isotope Separation System) and performed measurements of lifetimes and hyperfine structures of some platinum and iridium neutron-rich radioactive isotopes by applying multi-nucleon transfer reactions and in-gas laser ionization and spectroscopy (IGLIS) methods. In this report, recent physics results, updated KISS performance, and future's research plan including a challenge of a systematic mass measurement with MRTOF (Multi-Reflection Time-Of-Flight mass spectrograph) are presented.

Antimicrobial proteins: From old proteins, new tricks.

PubMed

Smith, Valerie J; Dyrynda, Elisabeth A

2015-12-01

This review describes the main types of antimicrobial peptides (AMPs) synthesised by crustaceans, primarily those identified in shrimp, crayfish, crab and lobster. It includes an overview of their range of microbicidal activities and the current landscape of our understanding of their gene expression patterns in different body tissues. It further summarises how their expression might change following various types of immune challenges. The review further considers proteins or protein fragments from crustaceans that have antimicrobial properties but are more usually associated with other biological functions, or are derived from such proteins. It discusses how these unconventional AMPs might be generated at, or delivered to, sites of infection and how they might contribute to crustacean host defence in vivo. It also highlights recent work that is starting to reveal the extent of multi-functionality displayed by some decapod AMPs, particularly their participation in other aspects of host protection. Examples of such activities include proteinase inhibition, phagocytosis, antiviral activity and haematopoiesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Changes in Children's Autonomous Motivation toward Physical Education during Transition from Elementary to Secondary School: A Self-Determination Perspective

ERIC Educational Resources Information Center

Rutten, Cindy; Boen, Filip; Vissers, Nathalie; Seghers, Jan

2015-01-01

Based on Self-Determination Theory (Deci & Ryan, 2000), this study tested whether changes in autonomous motivation toward physical education (AMPE) during the transition from elementary to secondary school can be predicted by changes in perceived need support from the physical education (PE) teacher and perceived physical school environment.…

Aging management program of the reactor building concrete at Point Lepreau Generating Station

NASA Astrophysics Data System (ADS)

Aldea, C.-M.; Shenton, B.; Demerchant, M. M.; Gendron, T.

2011-04-01

In order for New Brunswick Power Nuclear (NBPN) to control the risks of degradation of the concrete reactor building at the Point Lepreau Generating Station (PLGS) the development of an aging management plan (AMP) was initiated. The intention of this plan was to determine the requirements for specific structural components of concrete of the reactor building that require regular inspection and maintenance to ensure the safe and reliable operation of the plant. The document is currently in draft form and presents an integrated methodology for the application of an AMP for the concrete of the reactor building. The current AMP addresses the reactor building structure and various components, such as joint sealant and liners that are integral to the structure. It does not include internal components housed within the structure. This paper provides background information regarding the document developed and the strategy developed to manage potential degradation of the concrete of the reactor building, as well as specific programs and preventive and corrective maintenance activities initiated.

A possible mechanism for improvement by a cognition-enhancer nefiracetam of spatial memory function and cAMP-mediated signal transduction system in sustained cerebral ischaemia in rats

PubMed Central

Takeo, Satoshi; Niimura, Makiko; Miyake-Takagi, Keiko; Nagakura, Akira; Fukatsu, Tomoko; Ando, Tsuyoshi; Takagi, Norio; Tanonaka, Kouichi; Hara, Junko

2003-01-01

Accumulated evidence indicates that the adenylyl cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-responsive element binding protein (CREB) signal transduction system may be linked to learning and memory function. The effects of nefiracetam, which has been developed as a cognition enhancer, on spatial memory function and the AC/cAMP/PKA/CREB signal transduction system in rats with sustained cerebral ischaemia were examined. Microsphere embolism (ME)-induced sustained cerebral ischaemia was produced by injection of 700 microspheres (48 μm in diameter) into the right hemisphere of rats. Daily oral administration of nefiracetam (10 mg kg−1 day−1) was started from 15 h after the operation. The delayed treatment with nefiracetam attenuated the ME-induced prolongation of the escape latency in the water maze task that was examined on day 7 to 9 after ME, but it did not reduce the infarct size. ME decreased Ca2+/calmodulin (CaM)-stimulated AC (AC-I) activity, cAMP content, cytosolic PKA Cβ level, nuclear PKA Cα and Cβ levels, and reduced the phosphorylation and DNA-binding activity of CREB in the nucleus in the right parietal cortex and hippocampus on day 3 after ME. The ME-induced changes in these variables did not occur by the delayed treatment with nefiracetam. These results suggest that nefiracetam preserved cognitive function, or prevented cognitive dysfunction, after sustained cerebral ischaemia and that the effect is, in part, attributable to the prevention of the ischaemia-induced impairment of the AC/cAMP/PKA/CREB signal transduction pathway. PMID:12598418

Inhibition of Src Family Kinases by a Combinatorial Action of 5′-AMP and Small Heat Shock Proteins, Identified from the Adult Heart

PubMed Central

Kasi, Vijaykumar S.; Kuppuswamy, Dhandapani

1999-01-01

Src family kinases are implicated in cellular proliferation and transformation. Terminally differentiated myocytes have lost the ability to proliferate, indicating the existence of a down-regulatory mechanism(s) for these mitogenic kinases. Here we show that feline cardiomyocyte lysate contains thermostable components that inhibit c-Src kinase in vitro. This inhibitory activity, present predominantly in heart tissue, involves two components acting combinatorially. After purification by sequential chromatography, one component was identified by mass and nuclear magnetic resonance spectroscopies as 5′-AMP, while the other was identified by peptide sequencing as a small heat shock protein (sHSP). 5′-AMP and to a lesser extent 5′-ADP inhibit c-Src when combined with either HSP-27 or HSP-32. Other HSPs, including αB-crystallin, HSP-70, and HSP-90, did not exhibit this effect. The inhibition, observed preferentially on Src family kinases and independent of the Src tyrosine phosphorylation state, occurs via a direct interaction of the c-Src catalytic domain with the inhibitory components. Our study indicates that sHSPs increase the affinity of 5′-AMP for the c-Src ATP binding site, thereby facilitating the inhibition. In vivo, elevation of ATP levels in the cardiomyocytes results in the tyrosine phosphorylation of cellular proteins including c-Src at the activatory site, and this effect is blocked when the 5′-AMP concentration is raised. Thus, this study reveals a novel role for sHSPs and 5′-AMP in the regulation of Src family kinases, presumably for the maintenance of the terminally differentiated state. PMID:10490624

The Hippo pathway mediates inhibition of vascular smooth muscle cell proliferation by cAMP.

PubMed

Kimura, Tomomi E; Duggirala, Aparna; Smith, Madeleine C; White, Stephen; Sala-Newby, Graciela B; Newby, Andrew C; Bond, Mark

2016-01-01

Inhibition of vascular smooth muscle cell (VSMC) proliferation by intracellular cAMP prevents excessive neointima formation and hence angioplasty restenosis and vein-graft failure. These protective effects are mediated via actin-cytoskeleton remodelling and subsequent regulation of gene expression by mechanisms that are incompletely understood. Here we investigated the role of components of the growth-regulatory Hippo pathway, specifically the transcription factor TEAD and its co-factors YAP and TAZ in VSMC. Elevation of cAMP using forskolin, dibutyryl-cAMP or the physiological agonists, Cicaprost or adenosine, significantly increased phosphorylation and nuclear export YAP and TAZ and inhibited TEAD-luciferase report gene activity. Similar effects were obtained by inhibiting RhoA activity with C3-transferase, its downstream kinase, ROCK, with Y27632, or actin-polymerisation with Latrunculin-B. Conversely, expression of constitutively-active RhoA reversed the inhibitory effects of forskolin on TEAD-luciferase. Forskolin significantly inhibited the mRNA expression of the pro-mitogenic genes, CCN1, CTGF, c-MYC and TGFB2 and this was reversed by expression of constitutively-active YAP or TAZ phospho-mutants. Inhibition of YAP and TAZ function with RNAi or Verteporfin significantly reduced VSMC proliferation. Furthermore, the anti-mitogenic effects of forskolin were reversed by overexpression of constitutively-active YAP or TAZ. Taken together, these data demonstrate that cAMP-induced actin-cytoskeleton remodelling inhibits YAP/TAZ-TEAD dependent expression of pro-mitogenic genes in VSMC. This mechanism contributes novel insight into the anti-mitogenic effects of cAMP in VSMC and suggests a new target for intervention. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Probiotics for the treatment of Clostridium difficile associated disease

PubMed Central

Fitzpatrick, Leo R

2013-01-01

The purpose of this review paper is to update the current and potential future role of probiotics for Clostridium difficile-associated disease (CDAD). Included in this review, is an update on the testing of newer probiotics (e.g., Bacillus coagulans GBI-30, 6086) in animal models of CDAD. There is a focus on the modulation of signal transduction pathways (i.e., transcription factors like cAMP response element-binding, activator protein 1, and nuclear factor kappa B), as well as the inhibition of certain kinases (e.g., p38 mitogen activated protein kinases) by probiotics. Inhibition of signal transduction by probiotics, such as Saccharomyces boulardii, result in multiple effects on intestinal fluid secretion, neutrophil influx into the colon, inflammation, and colonocyte apoptosis that may positively impact CDAD. Recent clinical approaches with probiotics, for the prevention of primary and recurrent CDAD, are also summarized in this review paper. Future directions for the treatment of CDAD by probiotics are also mentioned in this review. In particular, the use of multi-strain probiotic formulations such as Ecologic® AAD and VSL #3® may represent a rationale pharmacological approach, particularly as adjunctive therapies for CDAD. Understanding the mechanistic basis of CDAD, and how probiotics interfere at ceratin steps in the pathogenic process, may also present the opportunity to design other multi-strain probiotics that could have a future impact on CDAD. PMID:23946887

77 FR 29701 - Impact of Construction (Under a Combined License) of New Nuclear Power Plant Units on Operating...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-18

... New Nuclear Power Plant Units on Operating Units at Multi-Unit Sites AGENCY: Nuclear Regulatory... construct and operate new nuclear power plants (NPPs) on multi-unit sites to provide an evaluation of the... License) of New Nuclear Power Plants on Operating Units at Multi-Unit Sites (Package). ML112630039 Federal...

Modeling and simulation challenges pursued by the Consortium for Advanced Simulation of Light Water Reactors (CASL)

NASA Astrophysics Data System (ADS)

Turinsky, Paul J.; Kothe, Douglas B.

2016-05-01

The Consortium for the Advanced Simulation of Light Water Reactors (CASL), the first Energy Innovation Hub of the Department of Energy, was established in 2010 with the goal of providing modeling and simulation (M&S) capabilities that support and accelerate the improvement of nuclear energy's economic competitiveness and the reduction of spent nuclear fuel volume per unit energy, and all while assuring nuclear safety. To accomplish this requires advances in M&S capabilities in radiation transport, thermal-hydraulics, fuel performance and corrosion chemistry. To focus CASL's R&D, industry challenge problems have been defined, which equate with long standing issues of the nuclear power industry that M&S can assist in addressing. To date CASL has developed a multi-physics ;core simulator; based upon pin-resolved radiation transport and subchannel (within fuel assembly) thermal-hydraulics, capitalizing on the capabilities of high performance computing. CASL's fuel performance M&S capability can also be optionally integrated into the core simulator, yielding a coupled multi-physics capability with untapped predictive potential. Material models have been developed to enhance predictive capabilities of fuel clad creep and growth, along with deeper understanding of zirconium alloy clad oxidation and hydrogen pickup. Understanding of corrosion chemistry (e.g., CRUD formation) has evolved at all scales: micro, meso and macro. CFD R&D has focused on improvement in closure models for subcooled boiling and bubbly flow, and the formulation of robust numerical solution algorithms. For multiphysics integration, several iterative acceleration methods have been assessed, illuminating areas where further research is needed. Finally, uncertainty quantification and data assimilation techniques, based upon sampling approaches, have been made more feasible for practicing nuclear engineers via R&D on dimensional reduction and biased sampling. Industry adoption of CASL's evolving M&S capabilities, which is in progress, will assist in addressing long-standing and future operational and safety challenges of the nuclear industry.

A Fusion Nuclear Science Facility for a fast-track path to DEMO

DOE PAGES

Garofalo, Andrea M.; Abdou, M.; Canik, John M.; ...

2014-10-01

An accelerated fusion energy development program, a “fast-track” approach, requires developing an understanding of fusion nuclear science (FNS) in parallel with research on ITER to study burning plasmas. A Fusion Nuclear Science Facility (FNSF) in parallel with ITER provides the capability to resolve FNS feasibility issues related to power extraction, tritium fuel sustainability, and reliability, and to begin construction of DEMO upon the achievement of Q~10 in ITER. Fusion nuclear components, including the first wall (FW)/blanket, divertor, heating/fueling systems, etc. are complex systems with many inter-related functions and different materials, fluids, and physical interfaces. These in-vessel nuclear components must operatemore » continuously and reliably with: (a) Plasma exposure, surface particle & radiation loads, (b) High energy 2 neutron fluxes and their interactions in materials (e.g. peaked volumetric heating with steep gradients, tritium production, activation, atomic displacements, gas production, etc.), (c) Strong magnetic fields with temporal and spatial variations (electromagnetic coupling to the plasma including off-normal events like disruptions), and (d) a High temperature, high vacuum, chemically active environment. While many of these conditions and effects are being studied with separate and multiple effect experimental test stands and modeling, fusion nuclear conditions cannot be completely simulated outside the fusion environment. This means there are many new multi-physics, multi-scale phenomena and synergistic effects yet to be discovered and accounted for in the understanding, design and operation of fusion as a self-sustaining, energy producing system, and significant experimentation and operational experience in a true fusion environment is an essential requirement. In the following sections we discuss the FNSF objectives, describe the facility requirements and a facility concept and operation approach that can accomplish those objectives, and assess the readiness to construct with respect to several key FNSF issues: materials, steady-state operation, disruptions, power exhaust, and breeding blanket. Finally we present our conclusions.« less

Identical plasmid AmpC beta-lactamase genes and plasmid types in E. coli isolates from patients and poultry meat in the Netherlands.

PubMed

Voets, Guido M; Fluit, Ad C; Scharringa, Jelle; Schapendonk, Claudia; van den Munckhof, Thijs; Leverstein-van Hall, Maurine A; Stuart, James Cohen

2013-11-01

The increasing prevalence of third-generation cephalosporin-resistant Enterobacteriaceae is a worldwide problem. Recent studies showed that poultry meat and humans share identical Extended-Spectrum Beta-Lactamase genes, plasmid types, and Escherichia coli strain types, suggesting that transmission from poultry meat to humans may occur. The aim of this study was to compare plasmid-encoded Ambler class C beta-lactamase (pAmpC) genes, their plasmids, and bacterial strain types between E. coli isolates from retail chicken meat and clinical isolates in the Netherlands. In total, 98 Dutch retail chicken meat samples and 479 third-generation cephalosporin non-susceptible human clinical E. coli isolates from the same period were screened for pAmpC production. Plasmid typing was performed using PCR-based replicon typing (PBRT). E coli strains were compared using Multi-Locus-Sequence-Typing (MLST). In 12 of 98 chicken meat samples (12%), pAmpC producing E. coli were detected (all blaCMY-2). Of the 479 human E. coli, 25 (5.2%) harboured pAmpC genes (blaCMY-2 n = 22, blaACT n = 2, blaMIR n = 1). PBRT showed that 91% of poultry meat isolates harboured blaCMY-2 on an IncK plasmid, and 9% on an IncI1 plasmid. Of the human blaCMY-2 producing isolates, 42% also harboured blaCMY-2 on an IncK plasmid, and 47% on an IncI1 plasmid. Thus, 68% of human pAmpC producing E. coli have the same AmpC gene (blaCMY-2) and plasmid type (IncI1 or IncK) as found in poultry meat. MLST showed one cluster containing one human isolate and three meat isolates, with an IncK plasmid. These findings imply that a foodborne transmission route of blaCMY-2 harbouring plasmids cannot be excluded and that further evaluation is required. © 2013.

Membrane and Integrative Nuclear Fibroblastic Growth Factor Receptor (FGFR) Regulation of FGF-23*

PubMed Central

Han, Xiaobin; Xiao, Zhousheng; Quarles, L. Darryl

2015-01-01

Fibroblastic growth factor receptor 1 (FGFR1) signaling pathways are implicated in the regulation of FGF-23 gene transcription, but the molecular pathways remain poorly defined. We used low molecular weight (LMW, 18 kDa) FGF-2 and high molecular weight (HMW) FGF-2 isoforms, which, respectively, activate cell surface FGF receptors and intranuclear FGFR1, to determine the roles of membrane FGFRs and integrative nuclear FGFR1 signaling (INFS) in the regulation of FGF-23 gene transcription in osteoblasts. We found that LMW-FGF-2 induced NFAT and Ets1 binding to conserved cis-elements in the proximal FGF-23 promoter and stimulated FGF-23 promoter activity through PLCγ/calcineurin/NFAT and MAPK pathways in SaOS-2 and MC3T3-E1 osteoblasts. In contrast, HMW-FGF-2 stimulated FGF-23 promoter activity in osteoblasts through a cAMP-dependent binding of FGFR1 and cAMP-response element-binding protein (CREB) to a conserved cAMP response element (CRE) contiguous with the NFAT binding site in the FGF-23 promoter. Mutagenesis of the NFAT and CRE binding sites, respectively, inhibited the effects of LMW-FGF-2 and HMW-FGF-23 to stimulate FGF-23 promoter activity. FGF-2 activation of both membrane FGFRs and INFS-dependent FGFR1 pathways may provide a means to integrate systemic and local regulation of FGF-23 transcription under diverse physiological and pathological conditions. PMID:25752607

Differences in the motor unit firing rates and amplitudes in relation to recruitment thresholds during submaximal contractions of the first dorsal interosseous between chronically resistance trained and physically active men.

PubMed

Sterczala, Adam J; Miller, Jonathan D; Trevino, Michael A; Dimmick, Hannah L; Herda, Trent J

2018-02-26

Previous investigations report no changes in motor unit (MU) firing rates during submaximal contractions following resistance training. These investigations did not account for MU recruitment or examine firing rates as a function of recruitment threshold (REC).Therefore, MU recruitment and firing rates in chronically resistance trained (RT) and physically active controls (CON) were examined. Surface electromyography signals were collected from the first dorsal interosseous (FDI) during isometric muscle actions at 40% and 70% maximal voluntary contraction (MVC). For each MU, force at REC, mean firing rate (MFR) during the steady force, and MU action potential amplitude (MUAP_AMP) were analyzed. For each individual and contraction, the MFRs were linearly regressed against REC, whereas, exponential models were applied to the MFR vs. MUAP_AMP and MUAP_AMP vs. REC relationships with the y-intercepts and slopes (linear) and A and B terms (exponential) calculated. For the 40% MVC, the RT group had less negative slopes (p=0.001) and lower y-intercepts (p=0.006) of the MFR vs. REC relationships and lower B terms (p=0.011) of the MUAP_AMP vs. REC relationships. There were no differences in either relationship between groups for the 70% MVC. During the 40% MVC, the RT had a smaller range of MFRs and MUAP_AMPS in comparison to the CON, likely due to reduced MU recruitment. The RT had lower MFRs and recruitment during the 40% MVC that may indicate a leftward shift in the force-frequency relationship, and thus require less excitation to the motoneuron pool to match the same relative force.

Lattice QCD input for nuclear structure and reactions

NASA Astrophysics Data System (ADS)

Davoudi, Zohreh

2018-03-01

Explorations of the properties of light nuclear systems beyond their lowestlying spectra have begun with Lattice Quantum Chromodynamics. While progress has been made in the past year in pursuing calculations with physical quark masses, studies of the simplest nuclear matrix elements and nuclear reactions at heavier quark masses have been conducted, and several interesting results have been obtained. A community effort has been devoted to investigate the impact of such Quantum Chromodynamics input on the nuclear many-body calculations. Systems involving hyperons and their interactions have been the focus of intense investigations in the field, with new results and deeper insights emerging. While the validity of some of the previous multi-nucleon studies has been questioned during the past year, controversy remains as whether such concerns are relevant to a given result. In an effort to summarize the newest developments in the field, this talk will touch on most of these topics.

Computing Properties of Hadrons, Nuclei and Nuclear Matter from Quantum Chromodynamics (LQCD)

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

Negele, John W.

Building on the success of two preceding generations of Scientific Discovery through Advanced Computing (SciDAC) projects, this grant supported the MIT component (P.I. John Negele) of a multi-institutional SciDAC-3 project that also included Brookhaven National Laboratory, the lead laboratory with P. I. Frithjof Karsch serving as Project Director, Thomas Jefferson National Accelerator Facility with P. I. David Richards serving as Co-director, University of Washington with P. I. Martin Savage, University of North Carolina with P. I. Rob Fowler, and College of William and Mary with P. I. Andreas Stathopoulos. Nationally, this multi-institutional project coordinated the software development effort that themore » nuclear physics lattice QCD community needs to ensure that lattice calculations can make optimal use of forthcoming leadership-class and dedicated hardware, including that at the national laboratories, and to exploit future computational resources in the Exascale era.« less

A randomized, controlled study to evaluate the role of an in-home asthma disease management program provided by respiratory therapists in improving outcomes and reducing the cost of care.

PubMed

Shelledy, David C; Legrand, Terry S; Gardner, Donna D; Peters, Jay I

2009-03-01

Asthma management programs (AMP) may reduce costs and improve outcomes in patients with moderate to severe asthma. However, it is not known which personnel are best able to deliver such interventions and what settings are most effective. The purpose of this study was to compare the effects of an in-home AMP provided by respiratory therapists (RTs) to an AMP provided by nurses (RNs) and to usual care (UC) provided in physician offices or clinics. Subjects (age 18-64) who had been admitted to the emergency department (ED) or hospital for acute asthma exacerbation were randomized to three groups: AMP-RT, AMP-RN or UC. The AMP groups received five (5) weekly home visits to provide assessment and instruction; the UC group was instructed to return to their physician for routine follow-up. Outcomes assessed at 6 months included hospitalizations, in patient days, hospitalization cost, ED visits and cost, clinic visits, pulmonary function, symptoms, health related quality of life (HRQOL), asthma episode self-management score (AESM), environmental assessment, and patient satisfaction (PS). Variables were compared using ANOVA with a Neuman-Keuls follow-up for multiple comparisons using an intent-to-treat approach. Upon enrollment, (n = 159) there were no differences (p > .05) between groups for age, gender, pulmonary function or HRQOL (SF-36 and St. Georges Respiratory Questionnaire - SGRQ). At 6 months, both AMP groups (AMP-RN n = 54; AMP-RT n = 46) had significantly fewer (p < 0.05) hospitalizations and in-patient days, lower hospitalization costs, and greater HRQOL physical component summary change scores (PCS) and PS than UC (n = 59). AMP-RT also had greater PEFR, SGRQ Total and SGRQ Symptoms change scores when compared to UC and significantly better AESM and PS scores as compared to AMP-RN and UC. An in-home asthma management program can be effectively delivered by respiratory therapists and may reduce hospitalizations, in-patient days, cost and improve measures of HRQOL and PS in a population prone to asthma exacerbation.

Understanding Core-Collapse Supernovae

NASA Astrophysics Data System (ADS)

Hix, W. R.; Lentz, E. J.; Baird, M.; Messer, O. E. B.; Mezzacappa, A.; Lee, C.-T.; Bruenn, S. W.; Blondin, J. M.; Marronetti, P.

2010-03-01

Our understanding of core-collapse supernovae continues to improve as better microphysics is included in increasingly realistic neutrino-radiationhydrodynamic simulations. Recent multi-dimensional models with spectral neutrino transport, which slowly develop successful explosions for a range of progenitors between 12 and 25 solar mass, have motivated changes in our understanding of the neutrino reheating mechanism. In a similar fashion, improvements in nuclear physics, most notably explorations of weak interactions on nuclei and the nuclear equation of state, continue to refine our understanding of how supernovae explode. Recent progresses on both the macroscopic and microscopic effects that affect core-collapse supernovae are discussed.

AMP-activated protein kinase is involved in the activation of the Fanconi anemia/BRCA pathway in response to DNA interstrand crosslinks

PubMed Central

Hwang, Soo Kyung; Kim, Bong Sub; Kim, Hyoun Geun; Choi, Hae In; Kim, Jong Heon; Goh, Sung Ho; Lee, Chang-Hun

2016-01-01

Fanconi anemia complementation group (FANC) proteins constitute the Fanconi Anemia (FA)/BRCA pathway that is activated in response to DNA interstrand crosslinks (ICLs). We previously performed yeast two-hybrid screening to identify novel FANC-interacting proteins and discovered that the alpha subunit of AMP-activated protein kinase (AMPKα1) was a candidate binding partner of the FANCG protein, which is a component of the FA nuclear core complex. We confirmed the interaction between AMPKα and both FANCG using co-immunoprecipitation experiments. Additionally, we showed that AMPKα interacted with FANCA, another component of the FA nuclear core complex. AMPKα knockdown in U2OS cells decreased FANCD2 monoubiquitination and nuclear foci formation upon mitomycin C-induced ICLs. Furthermore, AMPKα knockdown enhanced cellular sensitivity to MMC. MMC treatment resulted in an increase in AMPKα phosphorylation/activation, indicating AMPK is involved in the cellular response to ICLs. FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway. Our data suggest AMPK is involved in the activation of the FA/BRCA pathway. PMID:27449087

Predicting the valley physics of silicon quantum dots directly from a device layout

NASA Astrophysics Data System (ADS)

Gamble, John King; Harvey-Collard, Patrick; Jacobson, N. Tobias; Bacewski, Andrew D.; Nielsen, Erik; Montaño, Inès; Rudolph, Martin; Carroll, Malcolm S.; Muller, Richard P.

Qubits made from electrostatically-defined quantum dots in Si-based systems are excellent candidates for quantum information processing applications. However, the multi-valley structure of silicon's band structure provides additional challenges for the few-electron physics critical to qubit manipulation. Here, we present a theory for valley physics that is predictive, in that we take as input the real physical device geometry and experimental voltage operation schedule, and with minimal approximation compute the resulting valley physics. We present both effective mass theory and atomistic tight-binding calculations for two distinct metal-oxide-semiconductor (MOS) quantum dot systems, directly comparing them to experimental measurements of the valley splitting. We conclude by assessing these detailed simulations' utility for engineering desired valley physics in future devices. Sandia is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the US Department of Energy's National Nuclear Security Administration under Contract No. DE-AC04-94AL85000. The authors gratefully acknowledge support from the Sandia National Laboratories Truman Fellowship Program, which is funded by the Laboratory Directed Research and Development (LDRD) Program.

Multi-Physics Simulation of TREAT Kinetics using MAMMOTH

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

DeHart, Mark; Gleicher, Frederick; Ortensi, Javier

With the advent of next generation reactor systems and new fuel designs, the U.S. Department of Energy (DOE) has identified the need for the resumption of transient testing of nuclear fuels. DOE has decided that the Transient Reactor Test Facility (TREAT) at Idaho National Laboratory (INL) is best suited for future testing. TREAT is a thermal neutron spectrum nuclear test facility that is designed to test nuclear fuels in transient scenarios. These specific fuels transient tests range from simple temperature transients to full fuel melt accidents. The current TREAT core is driven by highly enriched uranium (HEU) dispersed in amore » graphite matrix (1:10000 U-235/C atom ratio). At the center of the core, fuel is removed allowing for the insertion of an experimental test vehicle. TREAT’s design provides experimental flexibility and inherent safety during neutron pulsing. This safety stems from the graphite in the driver fuel having a strong negative temperature coefficient of reactivity resulting from a thermal Maxwellian shift with increased leakage, as well as graphite acting as a temperature sink. Air cooling is available, but is generally used post-transient for heat removal. DOE and INL have expressed a desire to develop a simulation capability that will accurately model the experiments before they are irradiated at the facility, with an emphasis on effective and safe operation while minimizing experimental time and cost. At INL, the Multi-physics Object Oriented Simulation Environment (MOOSE) has been selected as the model development framework for this work. This paper describes the results of preliminary simulations of a TREAT fuel element under transient conditions using the MOOSE-based MAMMOTH reactor physics tool.« less

Functional synergy of α-helical antimicrobial peptides and traditional antibiotics against Gram-negative and Gram-positive bacteria in vitro and in vivo.

PubMed

Feng, Q; Huang, Y; Chen, M; Li, G; Chen, Y

2015-01-01

In this study, the antimicrobial activities based on the synergistic effects of traditional antibiotics (imipenem, cefepime, levofloxacin hydrochloride and vancomycin) and antimicrobial peptides (AMPs; PL-5, PL-31, PL-32, PL-18, PL-29 and PL-26), alone or in combination, against three Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae and Staphylococcus epidermidis) and three Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae) were investigated. In addition, the antimicrobial activity that was based on the synergistic effects of levofloxacin hydrochloride and PL-5 against Staphylococcus aureus in vivo was explored in a mouse infection model. Traditional antibiotics and AMPs showed significant synergistic effects on the antibacterial activities against the different Gram-positive and Gram-negative bacteria in vitro. A strong synergistic effect in the PL-5 and levofloxacin hydrochloride combination against Staphylococcus aureus was observed in the mouse infection model in vivo. The mechanism of synergistic action was due to the different targets of AMPs and traditional antibiotics. The combination of AMPs and traditional antibiotics can dramatically enhance antimicrobial activity and may help prevent or delay the emergence of antibiotic resistance. Thus, this combination therapy could be a promising approach to treat bacterial infections, particularly mixed infections and multi-antibiotic-resistant infections, in the clinics.

Metabolic benefits of inhibiting cAMP-PDEs with resveratrol.

PubMed

Chung, Jay H

2012-10-01

Calorie restriction (CR) extends lifespan in species ranging from yeast to mammals. There is evidence that CR also protects against aging-related diseases in non-human primates. This has led to an intense interest in the development of CR-mimetics to harness the beneficial effects of CR to treat aging-related diseases. One CR-mimetic that has received a great deal of attention is resveratrol. Resveratrol extends the lifespan of obese mice and protects against obesity-related diseases such as type 2 diabetes. The specific mechanism of resveratrol action has been difficult to elucidate because resveratrol has a promiscuous target profile. A recent finding indicates that the metabolic effects of resveratrol may result from competitive inhibition of cAMP-degrading phosphodiesterases (PDEs), which increases cAMP levels. The cAMP-dependent pathways activate AMP-activated protein kinase (AMPK), which is essential for the metabolic effects of resveratrol. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including protection against diet-induced obesity and an increase in mitochondrial function, physical stamina and glucose tolerance in mice. This discovery suggests that PDE inhibitors may be useful for treating metabolic diseases associated with aging.

Fasting Induces Nuclear Factor E2-Related Factor 2 and ATP-Binding Cassette Transporters via Protein Kinase A and Sirtuin-1 in Mouse and Human

PubMed Central

Kulkarni, Supriya R.; Donepudi, Ajay C.; Xu, Jialin; Wei, Wei; Cheng, Qiuqiong C.; Driscoll, Maureen V.; Johnson, Delinda A.; Johnson, Jeffrey A.; Li, Xiaoling

2014-01-01

Abstract Aims: The purpose of this study was to determine whether 3′-5′-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and Sirtuin-1 (SIRT1) dependent mechanisms modulate ATP-binding Cassette (ABC) transport protein expression. ABC transport proteins (ABCC2–4) are essential for chemical elimination from hepatocytes and biliary excretion. Nuclear factor-E2 related-factor 2 (NRF2) is a transcription factor that mediates ABCC induction in response to chemical inducers and liver injury. However, a role for NRF2 in the regulation of transporter expression in nonchemical models of liver perturbation is largely undescribed. Results: Here we show that fasting increased NRF2 target gene expression through NRF2- and SIRT1–dependent mechanisms. In intact mouse liver, fasting induces NRF2 target gene expression by at least 1.5 to 5-fold. In mouse and human hepatocytes, treatment with 8-Bromoadenosine-cAMP, a cAMP analogue, increased NRF2 target gene expression and antioxidant response element activity, which was decreased by the PKA inhibitor, H-89. Moreover, fasting induced NRF2 target gene expression was decreased in liver and hepatocytes of SIRT1 liver-specific null mice and NRF2-null mice. Lastly, NRF2 and SIRT1 were recruited to MAREs and Antioxidant Response Elements (AREs) in the human ABCC2 promoter. Innovation: Oxidative stress mediated NRF2 activation is well described, yet the influence of basic metabolic processes on NRF2 activation is just emerging. Conclusion: The current data point toward a novel role of nutrient status in regulation of NRF2 activity and the antioxidant response, and indicates that cAMP/PKA and SIRT1 are upstream regulators for fasting-induced activation of the NRF2-ARE pathway. Antioxid. Redox Signal. 20, 15–30. PMID:23725046

Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases.

PubMed

Park, Sung-Jun; Ahmad, Faiyaz; Philp, Andrew; Baar, Keith; Williams, Tishan; Luo, Haibin; Ke, Hengming; Rehmann, Holger; Taussig, Ronald; Brown, Alexandra L; Kim, Myung K; Beaven, Michael A; Burgin, Alex B; Manganiello, Vincent; Chung, Jay H

2012-02-03

Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resveratrol result from competitive inhibition of cAMP-degrading phosphodiesterases, leading to elevated cAMP levels. The resulting activation of Epac1, a cAMP effector protein, increases intracellular Ca(2+) levels and activates the CamKKβ-AMPK pathway via phospholipase C and the ryanodine receptor Ca(2+)-release channel. As a consequence, resveratrol increases NAD(+) and the activity of Sirt1. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice. Therefore, administration of PDE4 inhibitors may also protect against and ameliorate the symptoms of metabolic diseases associated with aging. Copyright © 2012 Elsevier Inc. All rights reserved.

YC-1 potentiates cAMP-induced CREB activation and nitric oxide production in alveolar macrophages

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

Hwang, Tsong-Long, E-mail: htl@mail.cgu.edu.tw; Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan, Taiwan; Tang, Ming-Chi

2012-04-15

Alveolar macrophages play significant roles in the pathogenesis of several inflammatory lung diseases. Increases in exhaled nitric oxide (NO) are well documented to reflect disease severity in the airway. In this study, we investigated the effect of 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1), a known activator of soluble guanylyl cyclase, on prostaglandin (PG)E{sub 1} (a stable PGE{sub 2} analogue) and forskolin (a adenylate cyclase activator) induced NO production and inducible NO synthase (iNOS) expression in rat alveolar macrophages (NR8383). YC-1 did not directly cause NO production or iNOS expression, but drastically potentiated PGE{sub 1}- or forskolin-induced NO production and iNOS expression in NR8383more » alveolar macrophages. Combination treatment with YC-1 and PGE{sub 1} significantly increased phosphorylation of the cAMP response element-binding protein (CREB), but not nuclear factor (NF)-κB activation. The combined effect on NO production, iNOS expression, and CREB phosphorylation was reversed by a protein kinase (PK)A inhibitor (H89), suggesting that the potentiating functions were mediated through a cAMP/PKA signaling pathway. Consistent with this, cAMP analogues, but not the cGMP analogue, caused NO release, iNOS expression, and CREB activation. YC-1 treatment induced an increase in PGE{sub 1}-induced cAMP formation, which occurred through the inhibition of cAMP-specific phosphodiesterase (PDE) activity. Furthermore, the combination of rolipram (an inhibitor of PDE4), but not milronone (an inhibitor of PDE3), and PGE{sub 1} also triggered NO production and iNOS expression. In summary, YC-1 potentiates PGE{sub 1}-induced NO production and iNOS expression in alveolar macrophages through inhibition of cAMP PDE activity and activation of the cAMP/PKA/CREB signaling pathway. Highlights: ► YC-1 potentiated PGE1-induced iNOS expression in alveolar macrophages. ► The combination of YC-1 and PGE1 increased CREB but not NFκB activation. ► The combined effects were reversed by H89. ► The combination of rolipram and PGE1 triggered NO production and iNOS expression. ► Effect of YC-1 occurred through inhibition of cAMP-specific PDE.« less

[Physical activity in the prevention and treatment of diseases of affluence--the key role of AMP-activated protein kinase (AMPK)].

PubMed

Grochowska, Ewa; Jarzyna, Robert

2014-09-12

In developed countries, we can observe an increasing number of people with obesity, type 2 diabetes, dyslipidemia, hypertension and arteriosclerosis. The main reason for this phenomenon is the abnormal energy balance due to sedentary lifestyles. Cardiovascular diseases are the leading cause of death in many countries around the world, nowadays. In this paper, the impact of physical activity on the effectiveness of treatment and prevention of metabolic diseases and cancer is considered. Exercise is one of the factors activating 5'AMP-activated protein kinase (AMPK). This enzyme is crucial in maintaining the energy balance of the cell and the entire organism, and its activation results in excluding the anabolic and switching on the catabolic processes. It is believed that the activation of AMPK is responsible for most of the positive effects resulting from physical exercise. Although there are pharmacological methods of activation of this enzyme, they seem to be not as effective as physical exercise. Therefore, physical activity should be the most important form of prevention and treatment of metabolic diseases.

Differences in ability to perform activities of daily living among women with fibromyalgia: A cross-sectional study.

PubMed

von Bülow, Cecilie; Amris, Kirstine; la Cour, Karen; Danneskiold-Samsøe, Bente; Ejlersen, Eva Wæhrens

2015-11-01

To investigate whether the Assessment of Motor and Process Skills (AMPS), the physical function subscales of the Fibromyalgia Impact Questionnaire (FIQ PF) and the 36-item Short Form (SF-36 PF) can identify subgroups of women with fibromyalgia with clinically relevant differences in ability to perform activities of daily living. Cross-sectional study. A total of 257 women with fibromyalgia. Participants were evaluated with the AMPS (measuring activities of daily living motor and activities of daily living process ability), FIQ and SF-36. AMPS independence cut-offs were used to divide the participants into 4 subgroups. Clinically relevant differences between subgroups were investigated based on the AMPS, FIQ PF and SF-36 PF. Participants in the 4 AMPS-derived subgroups demon-strated clinically relevant differences in observed activities of daily living motor and process ability. Neither the FIQ PF nor the SF-36 PF could differentiate between subgroups with clinically relevant differences in AMPS activities of daily living process ability. Activities of daily living process skills reflect underlying organizational and adaptive capacities of the individual and are relevant targets for interventions aiming at improving activities of daily living ability. Since self-report instruments do not capture differences in activities of daily living process ability, clinicians should include observations-based assessment of activities of daily living ability in order to individualize interventions offered.

78 FR 70076 - Aging Management of Internal Surfaces, Fire Water Systems, Atmospheric Storage Tanks, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-22

... Documents Access and Management System (ADAMS): You may access publicly available documents online in the... protection system piping, (d) revisions to the scope and inspection recommendations of the GALL Report AMP XI... NUCLEAR REGULATORY COMMISSION [NRC-2013-0068] Aging Management of Internal Surfaces, Fire Water...

ENVIRONMENTAL INFLUENCES ON GENETIC DIVERSITY OF CREEK CHUBS IN THE MID-ATLANTIC REGION OF THE USA

EPA Science Inventory

Analysis of genetic diversity within and among populations of stream fishes may provide a powerful method for assessing the status and trends in the condition of aquatic ecosystems. We analyzed mitochondrial DNA sequences (590 bases of cytochrome B) and nuclear DNA loci (109 amp...

78 FR 21980 - Aging Management of Internal Surfaces, Service Level III and Other Coatings, Atmospheric Storage...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-12

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0068] Aging Management of Internal Surfaces, Service Level... Interim Staff Guidance (LR-ISG), LR-ISG-2012-02, ``Aging Management of Internal Surfaces, Service Level... proposes to revise NRC staff-recommended aging management programs (AMP) and aging management review (AMR...

Peptides with Dual Antimicrobial and Anticancer Activities

NASA Astrophysics Data System (ADS)

Felício, Mário R.; Silva, Osmar N.; Gonçalves, Sônia; Santos, Nuno C.; Franco, Octávio L.

2017-02-01

In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of cancer, due to the instability in the immune system that allows cancer cells to proliferate. Likewise, the physical debility associated with cancer or with anticancer therapy itself often paves the way for opportunistic infections. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Highly cationic and amphipathic, they have demonstrated efficacy against both conditions, with the number of nature-driven or synthetically designed peptides increasing year by year. With similar properties, AMPs that can also act as ACPs are viewed as future chemotherapeutic drugs, with the advantage of low propensity to resistance, which started this paradigm in the pharmaceutical market. These peptides have already been described as molecules presenting killing mechanisms at the membrane level, but also acting towards intracellular targets, which increases their success comparatively to specific one-target drugs. This review will approach the desirable characteristics of small peptides that demonstrated dual activity against microbial infections and cancer, as well as the peptides engaged in clinical trials.

Covariant symplectic structure of the complex Monge-Ampère equation

NASA Astrophysics Data System (ADS)

Nutku, Y.

2000-04-01

The complex Monge-Ampère equation is invariant under arbitrary holomorphic changes of the independent variables with unit Jacobian. We present its variational formulation where the action remains invariant under this infinite group. The new Lagrangian enables us to obtain the first symplectic 2-form for the complex Monge-Ampère equation in the framework of the covariant Witten-Zuckerman approach to symplectic structure. We base our considerations on a reformulation of the Witten-Zuckerman theory in terms of holomorphic differential forms. The first closed and conserved Witten-Zuckerman symplectic 2-form for the complex Monge-Ampère equation is obtained in arbitrary dimension and for all cases elliptic, hyperbolic and homogeneous. The connection of the complex Monge-Ampère equation with Ricci-flat Kähler geometry suggests the use of the Hilbert action principle as an alternative variational formulation. However, we point out that Hilbert's Lagrangian is a divergence for Kähler metrics and serves as a topological invariant rather than yielding the Euclideanized Einstein field equations. Nevertheless, since the Witten-Zuckerman theory employs only the boundary terms in the first variation of the action, Hilbert's Lagrangian can be used to obtain the second Witten-Zuckerman symplectic 2-form. This symplectic 2-form vanishes on shell, thus defining a Lagrangian submanifold. In its derivation the connection of the second symplectic 2-form with the complex Monge-Ampère equation is indirect but we show that it satisfies all the properties required of a symplectic 2-form for the complex elliptic, or hyperbolic Monge-Ampère equation when the dimension of the complex manifold is 3 or higher. The complex Monge-Ampère equation admits covariant bisymplectic structure for complex dimension 3, or higher. However, in the physically interesting case of n=2 we have only one symplectic 2-form. The extension of these results to the case of complex Monge-Ampère-Liouville equation is also presented.

Design of a Resistively Heated Thermal Hydraulic Simulator for Nuclear Rocket Reactor Cores

NASA Technical Reports Server (NTRS)

Litchford, Ron J.; Foote, John P.; Ramachandran, Narayanan; Wang, Ten-See; Anghaie, Samim

2007-01-01

A preliminary design study is presented for a non-nuclear test facility which uses ohmic heating to replicate the thermal hydraulic characteristics of solid core nuclear reactor fuel element passages. The basis for this testing capability is a recently commissioned nuclear thermal rocket environments simulator, which uses a high-power, multi-gas, wall-stabilized constricted arc-heater to produce high-temperature pressurized hydrogen flows representative of reactor core environments, excepting radiation effects. Initially, the baseline test fixture for this non-nuclear environments simulator was configured for long duration hot hydrogen exposure of small cylindrical material specimens as a low cost means of evaluating material compatibility. It became evident, however, that additional functionality enhancements were needed to permit a critical examination of thermal hydraulic effects in fuel element passages. Thus, a design configuration was conceived whereby a short tubular material specimen, representing a fuel element passage segment, is surrounded by a backside resistive tungsten heater element and mounted within a self-contained module that inserts directly into the baseline test fixture assembly. With this configuration, it becomes possible to create an inward directed radial thermal gradient within the tubular material specimen such that the wall-to-gas heat flux characteristics of a typical fuel element passage are effectively simulated. The results of a preliminary engineering study for this innovative concept are fully summarized, including high-fidelity multi-physics thermal hydraulic simulations and detailed design features.

The Nuclotron-based Ion Collider Facility Project. The Physics Programme for the Multi-Purpose Detector

NASA Astrophysics Data System (ADS)

Geraksiev, N. S.; MPD Collaboration

2018-05-01

The Nuclotron-based Ion Collider fAcility (NICA) is a new accelerator complex being constructed at the Joint Institute for Nuclear Research (JINR). The general objective of the project is to provide beams for the experimental study of hot and dense strongly interacting QCD matter. The heavy ion programme includes two planned detectors: BM@N (Baryonic Matter at Nuclotron) a fixed target experiment with extracted Nuclotron beams; and MPD (MultiPurpose Detector) a collider mode experiment at NICA. The accelerated particles can range from protons and light nuclei to gold ions. Beam energies will span\\sqrt{s}=12-27 GeV with luminosity L ≥ 1 × 1030 cm‑2s‑1 and \\sqrt{{s}NN}=4-11 GeV and average luminosity L = 1 × 1027cm‑2 s ‑1(for 197Au79+), respectively. A third experiment for spin physics is planned with the SPD (Spin Physics Detector) at the NICA collider in polarized beams mode. A brief overview of the MPD is presented along with several observables in the MPD physics programme.

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

BRISC is a developmental prototype for a nextgeneration “systems-level” integrated performance and safety code (IPSC) for nuclear reactors. Its development served to demonstrate how a lightweight multi-physics coupling approach can be used to tightly couple the physics models in several different physics codes (written in a variety of languages) into one integrated package for simulating accident scenarios in a liquid sodium cooled “burner” nuclear reactor. For example, the RIO Fluid Flow and Heat transfer code developed at Sandia (SNL: Chris Moen, Dept. 08005) is used in BRISC to model fluid flow and heat transfer, as well as conduction heat transfermore » in solids. Because BRISC is a prototype, its most practical application is as a foundation or starting point for developing a true production code. The sub-codes and the associated models and correlations currently employed within BRISC were chosen to cover the required application space and demonstrate feasibility, but were not optimized or validated against experimental data within the context of their use in BRISC.« less

Regulatory motifs for CREB-binding protein and Nfe2l2 transcription factors in the upstream enhancer of the mitochondrial uncoupling protein 1 gene.

PubMed

Rim, Jong S; Kozak, Leslie P

2002-09-13

Thermogenesis against cold exposure in mammals occurs in brown adipose tissue (BAT) through mitochondrial uncoupling protein (UCP1). Expression of the Ucp1 gene is unique in brown adipocytes and is regulated tightly. The 5'-flanking region of the mouse Ucp1 gene contains cis-acting elements including PPRE, TRE, and four half-site cAMP-responsive elements (CRE) with BAT-specific enhancer elements. In the course of analyzing how these half-site CREs are involved in Ucp1 expression, we found that a DNA regulatory element for NF-E2 overlaps CRE2. Electrophoretic mobility shift assay and competition assays with the CRE2 element indicates that nuclear proteins from BAT, inguinal fat, and retroperitoneal fat tissue interact with the CRE2 motif (CGTCA) in a specific manner. A supershift assay using an antibody against the CRE-binding protein (CREB) shows specific affinity to the complex from CRE2 and nuclear extract of BAT. Additionally, Western blot analysis for phospho-CREB/ATF1 shows an increase in phosphorylation of CREB/ATF1 in HIB-1B cells after norepinephrine treatment. Transient transfection assay using luciferase reporter constructs also indicates that the two half-site CREs are involved in transcriptional regulation of Ucp1 in response to norepinephrine and cAMP. We also show that a second DNA regulatory element for NF-E2 is located upstream of the CRE2 region. This element, which is found in a similar location in the 5'-flanking region of the human and rodent Ucp1 genes, shows specific binding to rat and human NF-E2 by electrophoretic mobility shift assay with nuclear extracts from brown fat. Co-transfections with an Nfe2l2 expression vector and a luciferase reporter construct of the Ucp1 enhancer region provide additional evidence that Nfe2l2 is involved in the regulation of Ucp1 by cAMP-mediated signaling.

SHARP User Manual

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

Yu, Y. Q.; Shemon, E. R.; Thomas, J. W.

SHARP is an advanced modeling and simulation toolkit for the analysis of nuclear reactors. It is comprised of several components including physical modeling tools, tools to integrate the physics codes for multi-physics analyses, and a set of tools to couple the codes within the MOAB framework. Physics modules currently include the neutronics code PROTEUS, the thermal-hydraulics code Nek5000, and the structural mechanics code Diablo. This manual focuses on performing multi-physics calculations with the SHARP ToolKit. Manuals for the three individual physics modules are available with the SHARP distribution to help the user to either carry out the primary multi-physics calculationmore » with basic knowledge or perform further advanced development with in-depth knowledge of these codes. This manual provides step-by-step instructions on employing SHARP, including how to download and install the code, how to build the drivers for a test case, how to perform a calculation and how to visualize the results. Since SHARP has some specific library and environment dependencies, it is highly recommended that the user read this manual prior to installing SHARP. Verification tests cases are included to check proper installation of each module. It is suggested that the new user should first follow the step-by-step instructions provided for a test problem in this manual to understand the basic procedure of using SHARP before using SHARP for his/her own analysis. Both reference output and scripts are provided along with the test cases in order to verify correct installation and execution of the SHARP package. At the end of this manual, detailed instructions are provided on how to create a new test case so that user can perform novel multi-physics calculations with SHARP. Frequently asked questions are listed at the end of this manual to help the user to troubleshoot issues.« less

Multi-lobulation of the nucleus in prolonged S phase by nuclear expression of Chk tyrosine kinase.

PubMed

Nakayama, Yuji; Yamaguchi, Naoto

2005-04-01

Chk tyrosine kinase phosphorylates Src-family tyrosine kinases and suppresses their kinase activity. We recently showed that Chk localizes to the nucleus as well as the cytoplasm and inhibits cell proliferation. To investigate the role of nuclear Chk in proliferation, various Chk mutants were constructed and expressed. Nuclear localization of Chk-induced dynamic multi-lobulation of the nucleus and prolonged S phase of the cell cycle. The N-terminal domain of Chk and a portion of its kinase domain but not the kinase activity were responsible for induction of the multi-lobulation. Cell sorting analysis revealed that nuclear multi-lobulated cells were enriched in late S phase. Multi-lobulated nuclei were surrounded with lamin B1 that was particularly concentrated in concave regions of the nuclei. Furthermore, treatment with nocodazole or taxol disrupted multi-lobulation of the nucleus. These results suggest that nuclear multi-lobulation in late S phase, which is dependent on polymerization and depolymerization of microtubules, may be involved in nuclear Chk-induced inhibition of proliferation.

Hawaii State Department of Health

Science.gov Websites

. Nutrition Wellness Policy Links to Services & Resources Air Quality & Volcano Emissions (VOG) Aging Disease Framework 2013 Physical Activity & Nutrition (PAN) Plan Hawaii Journal of Medicine &

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

Arpiainen, Satu; Jaervenpaeae, Sanna-Mari; Manninen, Aki

The nutritional state of organisms and energy balance related diseases such as diabetes regulate the metabolism of xenobiotics such as drugs, toxins and carcinogens. However, the mechanisms behind this regulation are mostly unknown. The xenobiotic-metabolizing cytochrome P450 (CYP) 2A5 enzyme has been shown to be induced by fasting and by glucagon and cyclic AMP (cAMP), which mediate numerous fasting responses. Peroxisome proliferator-activated receptor {gamma} coactivator (PGC)-1{alpha} triggers many of the important hepatic fasting effects in response to elevated cAMP levels. In the present study, we were able to show that cAMP causes a coordinated induction of PGC-1{alpha} and CYP2A5 mRNAsmore » in murine primary hepatocytes. Furthermore, the elevation of the PGC-1{alpha} expression level by adenovirus mediated gene transfer increased CYP2A5 transcription. Co-transfection of Cyp2a5 5' promoter constructs with the PGC-1{alpha} expression vector demonstrated that PGC-1{alpha} is able to activate Cyp2a5 transcription through the hepatocyte nuclear factor (HNF)-4{alpha} response element in the proximal promoter of the Cyp2a5 gene. Chromatin immunoprecipitation assays showed that PGC-1{alpha} binds, together with HNF-4{alpha}, to the same region at the Cyp2a5 proximal promoter. In conclusion, PGC-1{alpha} mediates the expression of CYP2A5 induced by cAMP in mouse hepatocytes through coactivation of transcription factor HNF-4{alpha}. This strongly suggests that PGC-1{alpha} is the major factor mediating the fasting response of CYP2A5.« less

77 FR 14446 - Changes to the Generic Aging Lessons Learned (GALL) Report Revision 2 AMP XI.M41, “Buried and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0055] Changes to the Generic Aging Lessons Learned (GALL... Aging Lessons Learned (GALL) Report,'' and the NRC staff's aging management review procedure and... into ADAMS. II. Background The NRC issues LR-ISGs to communicate insights and lessons learned and to...

Designing Antibacterial Peptides with Enhanced Killing Kinetics

PubMed Central

Waghu, Faiza H.; Joseph, Shaini; Ghawali, Sanket; Martis, Elvis A.; Madan, Taruna; Venkatesh, Kareenhalli V.; Idicula-Thomas, Susan

2018-01-01

Antimicrobial peptides (AMPs) are gaining attention as substitutes for antibiotics in order to combat the risk posed by multi-drug resistant pathogens. Several research groups are engaged in design of potent anti-infective agents using natural AMPs as templates. In this study, a library of peptides with high sequence similarity to Myeloid Antimicrobial Peptide (MAP) family were screened using popular online prediction algorithms. These peptide variants were designed in a manner to retain the conserved residues within the MAP family. The prediction algorithms were found to effectively classify peptides based on their antimicrobial nature. In order to improve the activity of the identified peptides, molecular dynamics (MD) simulations, using bilayer and micellar systems could be used to design and predict effect of residue substitution on membranes of microbial and mammalian cells. The inference from MD simulation studies well corroborated with the wet-lab observations indicating that MD-guided rational design could lead to discovery of potent AMPs. The effect of the residue substitution on membrane activity was studied in greater detail using killing kinetic analysis. Killing kinetics studies on Gram-positive, negative and human erythrocytes indicated that a single residue change has a drastic effect on the potency of AMPs. An interesting outcome was a switch from monophasic to biphasic death rate constant of Staphylococcus aureus due to a single residue mutation in the peptide. PMID:29527201

Peptides from the scorpion Vaejovis punctatus with broad antimicrobial activity.

PubMed

Ramírez-Carreto, Santos; Jiménez-Vargas, Juana María; Rivas-Santiago, Bruno; Corzo, Gerardo; Possani, Lourival D; Becerril, Baltazar; Ortiz, Ernesto

2015-11-01

The antimicrobial potential of two new non-disulfide bound peptides, named VpAmp1.0 (LPFFLLSLIPSAISAIKKI, amidated) and VpAmp2.0 (FWGFLGKLAMKAVPSLIGGNKSSSK) is here reported. These are 19- and 25-aminoacid-long peptides with +2 and +4 net charges, respectively. Their sequences correspond to the predicted mature regions from longer precursors, putatively encoded by cDNAs derived from the venom glands of the Mexican scorpion Vaejovis punctatus. Both peptides were chemically synthesized and assayed against a variety of microorganisms, including pathogenic strains from clinical isolates and strains resistant to conventional antibiotics. Two shorter variants, named VpAmp1.1 (FFLLSLIPSAISAIKKI, amidated) and VpAmp2.1 (FWGFLGKLAMKAVPSLIGGNKK), were also synthesized and tested. The antimicrobial assays revealed that the four synthetic peptides effectively inhibit the growth of both Gram-positive (Staphylococcus aureus and Streptococcus agalactiaea) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria, with MICs in the range of 2.5-24.0 μM; yeasts (Candida albicans and Candida glabrata) with MICs of 3.1-50.0 μM; and two clinically isolated strains of Mycobacterium tuberculosis-including a multi-drug resistant one- with MICs in the range of 4.8-30.5 μM. A comparison between the activities of the original peptides and their derivatives gives insight into the structural/functional role of their distinctive residues. Copyright © 2015 Elsevier Inc. All rights reserved.

Automation system for measurement of gamma-ray spectra of induced activity for multi-element high volume neutron activation analysis at the reactor IBR-2 of Frank Laboratory of Neutron Physics at the joint institute for nuclear research

NASA Astrophysics Data System (ADS)

Pavlov, S. S.; Dmitriev, A. Yu.; Chepurchenko, I. A.; Frontasyeva, M. V.

2014-11-01

The automation system for measurement of induced activity of gamma-ray spectra for multi-element high volume neutron activation analysis (NAA) was designed, developed and implemented at the reactor IBR-2 at the Frank Laboratory of Neutron Physics. The system consists of three devices of automatic sample changers for three Canberra HPGe detector-based gamma spectrometry systems. Each sample changer consists of two-axis of linear positioning module M202A by DriveSet company and disk with 45 slots for containers with samples. Control of automatic sample changer is performed by the Xemo S360U controller by Systec company. Positioning accuracy can reach 0.1 mm. Special software performs automatic changing of samples and measurement of gamma spectra at constant interaction with the NAA database.

Quarkonium-nucleus bound states from lattice QCD

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

Beane, S.  R.; Chang, E.; Cohen, S.  D.

2015-06-11

Quarkonium-nucleus systems are composed of two interacting hadronic states without common valence quarks, which interact primarily through multi-gluon exchanges, realizing a color van der Waals force. We present lattice QCD calculations of the interactions of strange and charm quarkonia with light nuclei. Both the strangeonium-nucleus and charmonium-nucleus systems are found to be relatively deeply bound when the masses of the three light quarks are set equal to that of the physical strange quark. Extrapolation of these results to the physical light-quark masses suggests that the binding energy of charmonium to nuclear matter is B < 40 MeV.

Guide to Using Sierra

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

Shaw, Ryan Phillip; Agelastos, Anthony Michael; Miller, Joel D.

2015-03-01

Sierra is an engineering mechanics simulation code suite supporting the Nation's Nuclear Weapons mission as well as other customers. It has explicit ties to Sandia National Labs' workfow, including geometry and meshing, design and optimization, and visualization. Dis- tinguishing strengths include "application aware" development, scalability, SQA and V&V, multiple scales, and multi-physics coupling. This document is intended to help new and existing users of Sierra as a user manual and troubleshooting guide.

Guide to Using Sierra

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

Shaw, Ryan Phillip; Agelastos, Anthony Michael; Miller, Joel D.

2017-04-01

Sierra is an engineering mechanics simulation code suite supporting the Nation's Nuclear Weapons mission as well as other customers. It has explicit ties to Sandia National Labs' workfow, including geometry and meshing, design and optimization, and visualization. Dis- tinguishing strengths include "application aware" development, scalability, SQA and V&V, multiple scales, and multi-physics coupling. This document is intended to help new and existing users of Sierra as a user manual and troubleshooting guide.

Nuclear BK Channels Regulate Gene Expression via the Control of Nuclear Calcium Signaling

PubMed Central

Li, Boxing; Jie, Wei; Huang, Lianyan; Wei, Peng; Li, Shuji; Luo, Zhengyi; Friedman, Allyson K.; Meredith, Andrea L.; Han, Ming-Hu; Zhu, Xin-Hong; Gao, Tian-Ming

2014-01-01

Ion channels are essential for the regulation of neuronal functions. The significance of plasma membrane, mitochondrial, endoplasmic reticulum, and lysosomal ion channels in the regulation of Ca2+ is well established. In contrast, surprisingly less is known about the function of ion channels on the nuclear envelope (NE). Here we demonstrate the presence of functional large-conductance, calcium-activated potassium channels (BK channels) on the NE of rodent hippocampal neurons. Functionally blockade of nuclear BK channels (nBK channels) induces NE-derived Ca2+ release, nucleoplasmic Ca2+ elevation, and cAMP response element binding protein (CREB)-dependent transcription. More importantly, blockade of nBK channels regulates nuclear Ca2+-sensitive gene expression and promotes dendritic arborization in a nuclear Ca2+-dependent manner. These results suggest that nBK channel functions as a molecular linker between neuronal activity and nuclear Ca2+ to convey the signals from synapse to nucleus and is a new modulator for synaptic activity-dependent neuronal functions at the NE level. PMID:24952642

The phosphorylated C-terminus of cAR1 plays a role in cell-type-specific gene expression and STATa tyrosine phosphorylation.

PubMed

Briscoe, C; Moniakis, J; Kim, J Y; Brown, J M; Hereld, D; Devreotes, P N; Firtel, R A

2001-05-01

cAMP receptors mediate some signaling pathways via coupled heterotrimeric G proteins, while others are G-protein-independent. This latter class includes the activation of the transcription factors GBF and STATa. Within the cellular mounds formed by aggregation of Dictyostelium, micromolar levels of cAMP activate GBF function, thereby inducing the transcription of postaggregative genes and initiating multicellular differentiation. Activation of STATa, a regulator of culmination and ecmB expression, results from cAMP receptor-dependent tyrosine phosphorylation and nuclear localization, also in mound-stage cells. During mound development, the cAMP receptor cAR1 is in a low-affinity state and is phosphorylated on multiple serine residues in its C-terminus. This paper addresses possible roles of cAMP receptor phosphorylation in the cAMP-mediated stimulation of GBF activity, STATa tyrosine phosphorylation, and cell-type-specific gene expression. To accomplish this, we have expressed cAR1 mutants in a strain in which the endogenous cAMP receptors that mediate postaggregative gene expression in vivo are deleted. We then examined the ability of these cells to undergo morphogenesis and induce postaggregative and cell-type-specific gene expression and STATa tyrosine phosphorylation. Analysis of cAR1 mutants in which the C-terminal tail is deleted or the ligand-mediated phosphorylation sites are mutated suggests that the cAR1 C-terminus is not essential for GBF-mediated postaggregative gene expression or STATa tyrosine phosphorylation, but may play a role in regulating cell-type-specific gene expression and morphogenesis. A mutant receptor, in which the C-terminal tail is constitutively phosphorylated, exhibits constitutive activation of STATa tyrosine phosphorylation in pulsed cells in suspension and a significantly impaired ability to induce cell-type-specific gene expression. The constitutively phosphorylated receptor also exerts a partial dominant negative effect on multicellular development when expressed in wild-type cells. These findings suggest that the phosphorylated C-terminus of cAR1 may be involved in regulating aspects of receptor-mediated processes, is not essential for GBF function, and may play a role in mediating subsequent development. Copyright 2001 Academic Press.

CD73 and AMPD3 deficiency enhance metabolic performance via erythrocyte ATP that decreases hemoglobin oxygen affinity.

PubMed

O'Brien, William G; Berka, Vladimir; Tsai, Ah-Lim; Zhao, Zhaoyang; Lee, Cheng Chi

2015-08-07

Erythrocytes are the key target in 5'-AMP induced hypometabolism. To understand how regulation of endogenous erythrocyte AMP levels modulates systemic metabolism, we generated mice deficient in both CD73 and AMPD3, the key catabolic enzymes for extracellular and intra-erythrocyte AMP, respectively. Under physiological conditions, these mice displayed enhanced capacity for physical activity accompanied by significantly higher food and oxygen consumption, compared to wild type mice. Erythrocytes from Ampd3(-/-) mice exhibited higher half-saturation pressure of oxygen (p50) and about 3-fold higher levels of ATP and ADP, while they maintained normal 2,3-bisphosphoglycerate (2,3-BPG), methemoglobin levels and intracellular pH. The affinity of mammalian hemoglobin for oxygen is thought to be regulated primarily by 2,3-BPG levels and pH (the Bohr effect). However, our results show that increased endogenous levels of ATP and ADP, but not AMP, directly increase the p50 value of hemoglobin. Additionally, the rise in erythrocyte p50 directly correlates with an enhanced capability of systemic metabolism.

Attack on single Escherichia coli spheroplast by antimicrobial peptides

NASA Astrophysics Data System (ADS)

Sun, Tzu-Lin

Studies of the molecular mechanisms of antimicrobial peptides (AMPs) have mostly been performed with lipid bilayers, as a substitute for cell membrane. Hence, there is a persistent question as to whether the action of AMPs on bacterial membranes can be reproduced on lipid bilayers. Valuable information was obtained recently from observing the actions of AMPs on E. coli and Bacillus subtilis by time-lapse fluorescence microscopy. The goal of my dissertation is to study the direct action of AMPs on the cytoplasmic membranes by using E. coli spheroplasts, the cell form from which the outer membranes have been removed. The key question is how to reveal the response of the spheroplast to AMPs. In our previous work, the aspiration method on giant unilamellar vesicle (GUV) has been demonstrated as very effective for researching membrane effects induced by peptides. This method is able to measure the membrane expansion due to peptide binding and simultaneously monitor membrane permeability by using dye indicators. In this work, a spray method was developed for introducing AMPs and customized the experimental procedures for performing the experiments of E. coli spheroplasts. The living state of cytoplasmic membrane makes it difficult to deduce the molecular events from the response of live cells. Hence, the physical methods which have been developed for researching peptide activity on lipid bilayers were practiced first. These methods include X-ray diffraction (XRD), oriented circular dichroism (OCD) and GUV aspiration. These methods were practiced by studying the question as to why a hydrocarbon-stapled peptide NYAD-1 drug was reported to have membrane permeating property. Melittin was selected as the representative of AMPs for the E. coli spheroplast experiments. To better understand the characteristics of melittin, the melittin activity on model lipid membrane was examined before advancing to the spehroplast experiment. The melittin transmembrane was proposed by correlating melittin binding on a lipid vesicle (aspirated GUV imaging) with structural studies in multilayers (XRD and OCD). This behavior was further determined by using fluorescence indicator to track the melittin distribution. The toroidal structure of melittin pore was also detected by grazing-angle X-ray anomalous diffraction. In the studies of NAYD-1 and melittin on a model membrane, our discovery of AMP's transmembrane enables us to clarify the pore-formation mechanism which has been disputed for decades. In addition, our past work on the physical property of E. coli spheroplast cytoplasmic membrane has indicated the existence of a lipid reservoir. The lipid reservoir dominates the surface tension by balancing the membrane folds. Finally, we used the aspiration method to hold a spheroplast so as to measure the change of the spheroplast membrane area in response to the AMPs' binding. Further, a fluorescence indicator which is able to associate with AMPs was used to monitor the peptide distribution and another fluorescence dye to monitor the molecule leakage. The spheroplast study shows that there are similarities and differences between the responses of spheroplasts and GUVs. The recent findings on the unique properties of spheroplast membranes are the key for understanding these results. Our work of understanding the AMPs activity on membrane is potentially applicable in improving peptide drug design and delivery for disease treatment.

17beta-estradiol potently suppresses cAMP-induced insulin-like growth factor-I gene activation in primary rat osteoblast cultures

NASA Technical Reports Server (NTRS)

McCarthy, T. L.; Ji, C.; Shu, H.; Casinghino, S.; Crothers, K.; Rotwein, P.; Centrella, M.

1997-01-01

Insulin-like growth factor-I (IGF-I) is a key factor in bone remodeling. In osteoblasts, IGF-I synthesis is enhanced by parathyroid hormone and prostaglandin E2 (PGE2) through cAMP-activated protein kinase. In rats, estrogen loss after ovariectomy leads to a rise in serum IGF-I and an increase in bone remodeling, both of which are reversed by estrogen treatment. To examine estrogen-dependent regulation of IGF-I expression at the molecular level, primary fetal rat osteoblasts were co-transfected with the estrogen receptor (hER, to ensure active ER expression), and luciferase reporter plasmids controlled by promoter 1 of the rat IGF-I gene (IGF-I P1), used exclusively in these cells. As reported, 1 microM PGE2 increased IGF-I P1 activity by 5-fold. 17beta-Estradiol alone had no effect, but dose-dependently suppressed the stimulatory effect of PGE2 by up to 90% (ED50 approximately 0.1 nM). This occurred within 3 h, persisted for at least 16 h, required ER, and appeared specific, since 17alpha-estradiol was 100-300-fold less effective. By contrast, 17beta-estradiol stimulated estrogen response element (ERE)-dependent reporter expression by up to 10-fold. 17beta-Estradiol also suppressed an IGF-I P1 construct retaining only minimal promoter sequence required for cAMP-dependent gene activation, but did not affect the 60-fold increase in cAMP induced by PGE2. There is no consensus ERE in rat IGF-I P1, suggesting novel downstream interactions in the cAMP pathway that normally enhances IGF-I expression in skeletal cells. To explore this, nuclear extract from osteoblasts expressing hER were examined by electrophoretic mobility shift assay using the atypical cAMP response element in IGF-I P1. Estrogen alone did not cause DNA-protein binding, while PGE2 induced a characteristic gel shift complex. Co-treatment with both hormones caused a gel shift greatly diminished in intensity, consistent with their combined effects on IGF-I promoter activity. Nonetheless, hER did not bind IGF-I cAMP response element or any adjacent sequences. These results provide new molecular evidence that estrogen may temper the biological effects of hormones acting through cAMP to regulate skeletal IGF-I expression and activity.

Digital Signal Processing Methods for Safety Systems Employed in Nuclear Power Industry

NASA Astrophysics Data System (ADS)

Popescu, George

Some of the major safety concerns in the nuclear power industry focus on the readiness of nuclear power plant safety systems to respond to an abnormal event, the security of special nuclear materials in used nuclear fuels, and the need for physical security to protect personnel and reactor safety systems from an act of terror. Routine maintenance and tests of all nuclear reactor safety systems are performed on a regular basis to confirm the ability of these systems to operate as expected. However, these tests do not determine the reliability of these safety systems and whether the systems will perform for the duration of an accident and whether they will perform their tasks without failure after being engaged. This research has investigated the progression of spindle asynchronous error motion determined from spindle accelerations to predict bearings failure onset. This method could be applied to coolant pumps that are essential components of emergency core cooling systems at all nuclear power plants. Recent security upgrades mandated by the Nuclear Regulatory Commission and the Department of Homeland Security have resulted in implementation of multiple physical security barriers around all of the commercial and research nuclear reactors in the United States. A second part of this research attempts to address an increased concern about illegal trafficking of Special Nuclear Materials (SNM). This research describes a multi element scintillation detector system designed for non - invasive (passive) gamma ray surveillance for concealed SNM that may be within an area or sealed in a package, vehicle or shipping container. Detection capabilities of the system were greatly enhanced through digital signal processing, which allows the combination of two very powerful techniques: 1) Compton Suppression (CS) and 2) Pulse Shape Discrimination (PSD) with less reliance on complicated analog instrumentation.

NEAMS Update. Quarterly Report for October - December 2011.

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

Bradley, K.

2012-02-16

The Advanced Modeling and Simulation Office within the DOE Office of Nuclear Energy (NE) has been charged with revolutionizing the design tools used to build nuclear power plants during the next 10 years. To accomplish this, the DOE has brought together the national laboratories, U.S. universities, and the nuclear energy industry to establish the Nuclear Energy Advanced Modeling and Simulation (NEAMS) Program. The mission of NEAMS is to modernize computer modeling of nuclear energy systems and improve the fidelity and validity of modeling results using contemporary software environments and high-performance computers. NEAMS will create a set of engineering-level codes aimedmore » at designing and analyzing the performance and safety of nuclear power plants and reactor fuels. The truly predictive nature of these codes will be achieved by modeling the governing phenomena at the spatial and temporal scales that dominate the behavior. These codes will be executed within a simulation environment that orchestrates code integration with respect to spatial meshing, computational resources, and execution to give the user a common 'look and feel' for setting up problems and displaying results. NEAMS is building upon a suite of existing simulation tools, including those developed by the federal Scientific Discovery through Advanced Computing and Advanced Simulation and Computing programs. NEAMS also draws upon existing simulation tools for materials and nuclear systems, although many of these are limited in terms of scale, applicability, and portability (their ability to be integrated into contemporary software and hardware architectures). NEAMS investments have directly and indirectly supported additional NE research and development programs, including those devoted to waste repositories, safeguarded separations systems, and long-term storage of used nuclear fuel. NEAMS is organized into two broad efforts, each comprising four elements. The quarterly highlights October-December 2011 are: (1) Version 1.0 of AMP, the fuel assembly performance code, was tested on the JAGUAR supercomputer and released on November 1, 2011, a detailed discussion of this new simulation tool is given; (2) A coolant sub-channel model and a preliminary UO{sub 2} smeared-cracking model were implemented in BISON, the single-pin fuel code, more information on how these models were developed and benchmarked is given; (3) The Object Kinetic Monte Carlo model was implemented to account for nucleation events in meso-scale simulations and a discussion of the significance of this advance is given; (4) The SHARP neutronics module, PROTEUS, was expanded to be applicable to all types of reactors, and a discussion of the importance of PROTEUS is given; (5) A plan has been finalized for integrating the high-fidelity, three-dimensional reactor code SHARP with both the systems-level code RELAP7 and the fuel assembly code AMP. This is a new initiative; (6) Work began to evaluate the applicability of AMP to the problem of dry storage of used fuel and to define a relevant problem to test the applicability; (7) A code to obtain phonon spectra from the force-constant matrix for a crystalline lattice has been completed. This important bridge between subcontinuum and continuum phenomena is discussed; (8) Benchmarking was begun on the meso-scale, finite-element fuels code MARMOT to validate its new variable splitting algorithm; (9) A very computationally demanding simulation of diffusion-driven nucleation of new microstructural features has been completed. An explanation of the difficulty of this simulation is given; (10) Experiments were conducted with deformed steel to validate a crystal plasticity finite-element code for bodycentered cubic iron; (11) The Capability Transfer Roadmap was completed and published as an internal laboratory technical report; (12) The AMP fuel assembly code input generator was integrated into the NEAMS Integrated Computational Environment (NiCE). More details on the planned NEAMS computing environment is given; and (13) The NEAMS program website (neams.energy.gov) is nearly ready to launch.« less

An internet-supported school physical activity intervention in low socioeconomic status communities: results from the Activity and Motivation in Physical Education (AMPED) cluster randomised controlled trial.

PubMed

Lonsdale, Chris; Lester, Aidan; Owen, Katherine B; White, Rhiannon L; Peralta, Louisa; Kirwan, Morwenna; Diallo, Thierno M O; Maeder, Anthony J; Bennie, Andrew; MacMillan, Freya; Kolt, Gregory S; Ntoumanis, Nikos; Gore, Jennifer M; Cerin, Ester; Cliff, Dylan P; Lubans, David R

2017-10-09

Quality physical education (PE) is the cornerstone of comprehensive school physical activity (PA) promotion programmes. We tested the efficacy of a teacher professional learning intervention, delivered partially via the internet, designed to maximise opportunities for students to be active during PE lessons and enhance adolescents' motivation towards PE and PA. A two-arm cluster randomised controlled trial with teachers and Grade 8 students from secondary schools in low socioeconomic areas of Western Sydney, Australia. The Activity and Motivation in Physical Education (AMPED) intervention for secondary school PE teachers included workshops, online learning, implementation tasks and mentoring sessions. The primary outcome was the proportion of PE lesson time that students spent in moderate-to-vigorous physical activity (MVPA), measured by accelerometers at baseline, postintervention (7-8 months after baseline) and maintenance (14-15 months). Secondary outcomes included observed PE teachers' behaviour during lessons, students' leisure-time PA and students' motivation. Students (n=1421) from 14 schools completed baseline assessments and were included in linear mixed model analyses. The intervention had positive effects on students' MVPA during lessons. At postintervention, the adjusted mean difference in the proportion of lesson time spent in MVPA was 5.58% (p<0.001, approximately 4 min/lesson). During the maintenance phase, this effect was 2.64% (p<0.001, approximately 2 min/lesson). The intervention had positive effects on teachers' behaviour, but did not impact students' motivation. AMPED produced modest improvements in MVPA and compares favourably with previous interventions delivered exclusively face-to-face. Online teacher training could help facilitate widespread dissemination of professional learning interventions. ACTRN12614000184673. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

FOREWORD: International Summer School for Advanced Studies 'Dynamics of open nuclear systems' (PREDEAL12)

NASA Astrophysics Data System (ADS)

Delion, D. S.; Zamfir, N. V.; Raduta, A. R.; Gulminelli, F.

2013-02-01

This proceedings volume contains the invited lectures and contributions presented at the International Summer School on Nuclear Physics held at Trei Brazi, a summer resort of the Bioterra University, near the city of Predeal, Romania, on 9-20 July 2012. The long tradition of International Summer Schools on Nuclear Physics in Romania dates as far back as 1964, with the event being scheduled every two years. During this period of almost 50 years, many outstanding nuclear scientists have lectured on various topics related to nuclear physics and particle physics. This year we celebrate the 80th birthday of Aureliu Sandulescu, one of the founders of the Romanian school of theoretical nuclear physics. He was Serban Titeica's PhD student, one of Werner Heisenberg's PhD students, and he organized the first edition of this event. Aureliu Sandulescu's major contributions to the field of theoretical nuclear physics are related in particular to the prediction of cluster radioactivity, the physics of open quantum systems and the innovative technique of detecting superheavy nuclei using the double magic projectile 48Ca (Calcium), nowadays a widely used method at the JINR—Dubna and GSI—Darmstadt laboratories. The title of the event, 'Dynamics of Open Nuclear Systems', is in recognition of Aureliu Sandulescu's great personality. The lectures were attended by Romanian and foreign Master and PhD students and young researchers in nuclear physics. About 25 reputable professors and researchers in nuclear physics delivered lectures during this period. According to a well-established tradition, an interval of two hours was allotted for each lecture (including discussions). Therefore we kept a balance between the school and conference format. Two lectures were held during the morning and afternoon sessions. After lecture sessions, three or four oral contributions were given by young scientists. This was a good opportunity for them to present the results of their research in front of renowned professors and researchers in nuclear physics. This proceedings volume is organized into four chapters, which reflects the traditional chapter structure of nuclear physics textbooks, but seen from the perspective of open quantum systems: INuclear structure IIDecay processes IIINuclear reactions and astrophysics IVContributions The lectures and contributions are listed alphabetically by author within each chapter. The volume contains many comprehensive reviews related to the topics of the School. The first week of the School was focused on nuclear structure and decay phenomena, considering the nucleus as an open system. Experts in these fields lectured on cluster radioactivity, the stability of superheavy nuclei, alpha-decay fine structure, fission versus fusion, beta and double beta decay and pairing versus alpha-clustering. New experimental results related to the nuclear stability of low-lying and high spin states were also presented. Recent developments at JINR—Dubna and GSI—Darmstadt international laboratories were also reported by their current or former directors. The second week of the event was dedicated to the physics of exotic nuclei, heavy ion reactions and multi-fragmentation, symmetries and phase transitions of open quantum systems. The stability of the atomic nucleus is an important and always interesting discussion point, especially in the context of newly discovered nuclear systems close to the stability line, such as proton/neutron rich or superheavy nuclei. Several lectures and contributions were focused on nuclear structure models describing low-lying states. This includes the status of density functional theory, new developments in Bohr-Mottelsohn Hamiltonian and shell-model theory, proton-neutron correlations, shape coexistence, back-bending phenomena and the thermodynamics of open quantum systems. Open systems in astrophysics, such as supernovae and neutron stars, were presented in detail by several lecturers. Important topics connected to the status of the equation of state, hyperonic and quark matter and neutrino physics, as well as the applications of nuclear structure in astrophysics, were also on the School's agenda. There were many discussions and questions both during and after presentations. An open and friendly atmosphere characterized our School, although different opinions quite often divided the participants. Many discussions continued during coffee breaks and excursions organized in the beautiful surroundings. We hope that this proceedings volume will be useful for future reference to both young scientists and senior researchers working in various fields of nuclear physics. We cannot end without expressing our many thanks to the National Authority for Scientific Research and the Romanian Academy (Elias Foundation) for their financial support. We acknowledge the Horia Hulubei National Institute of Physics and Nuclear Engineering and Bioterra University for their important contribution in organizing the School. Guest Editors D S Delion, N V Zamfir, A R Raduta and F Gulminelli First Week International Summer School on Nuclear Physics: First Week Second Week International Summer School on Nuclear Physics: Second Week Sponsors Sponsor logoSponsor logoSponsor logoSponsor logoSponsor logo

Internet end-to-end performance monitoring for the High Energy Nuclear and Particle Physics community

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

Matthews, W.

2000-02-22

Modern High Energy Nuclear and Particle Physics (HENP) experiments at Laboratories around the world present a significant challenge to wide area networks. Petabytes (1015) or exabytes (1018) of data will be generated during the lifetime of the experiment. Much of this data will be distributed via the Internet to the experiment's collaborators at Universities and Institutes throughout the world for analysis. In order to assess the feasibility of the computing goals of these and future experiments, the HENP networking community is actively monitoring performance across a large part of the Internet used by its collaborators. Since 1995, the pingER projectmore » has been collecting data on ping packet loss and round trip times. In January 2000, there are 28 monitoring sites in 15 countries gathering data on over 2,000 end-to-end pairs. HENP labs such as SLAC, Fermi Lab and CERN are using Advanced Network's Surveyor project and monitoring performance from one-way delay of UDP packets. More recently several HENP sites have become involved with NLANR's active measurement program (AMP). In addition SLAC and CERN are part of the RIPE test-traffic project and SLAC is home for a NIMI machine. The large End-to-end performance monitoring infrastructure allows the HENP networking community to chart long term trends and closely examine short term glitches across a wide range of networks and connections. The different methodologies provide opportunities to compare results based on different protocols and statistical samples. Understanding agreement and discrepancies between results provides particular insight into the nature of the network. This paper will highlight the practical side of monitoring by reviewing the special needs of High Energy Nuclear and Particle Physics experiments and provide an overview of the experience of measuring performance across a large number of interconnected networks throughout the world with various methodologies. In particular, results from each project will be compared and disagreement will be analyzed. The goal is to address issues for improving understanding for gathering and analysis of accurate monitoring data, but the outlook for the computing goals of HENP will also be examined.« less

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

Merzari, E.; Yuan, Haomin; Kraus, A.

The NEAMS program aims to develop an integrated multi-physics simulation capability “pellet-to-plant” for the design and analysis of future generations of nuclear power plants. In particular, the Reactor Product Line code suite's multi-resolution hierarchy is being designed to ultimately span the full range of length and time scales present in relevant reactor design and safety analyses, as well as scale from desktop to petaflop computing platforms. Flow-induced vibration (FIV) is widespread problem in energy systems because they rely on fluid movement for energy conversion. Vibrating structures may be damaged as fatigue or wear occurs. Given the importance of reliable componentsmore » in the nuclear industry, flow-induced vibration has long been a major concern in safety and operation of nuclear reactors. In particular, nuclear fuel rods and steam generators have been known to suffer from flow-induced vibration and related failures. Advanced reactors, such as integral Pressurized Water Reactors (PWRs) considered for Small Modular Reactors (SMR), often rely on innovative component designs to meet cost and safety targets. One component that is the subject of advanced designs is the steam generator, some designs of which forego the usual shell-and-tube architecture in order to fit within the primary vessel. In addition to being more cost- and space-efficient, such steam generators need to be more reliable, since failure of the primary vessel represents a potential loss of coolant and a safety concern. A significant amount of data exists on flow-induced vibration in shell-and-tube heat exchangers, and heuristic methods are available to predict their occurrence based on a set of given assumptions. In contrast, advanced designs have far less data available. Advanced modeling and simulation based on coupled structural and fluid simulations have the potential to predict flow-induced vibration in a variety of designs, reducing the need for expensive experimental programs, especially at the design stage. Over the past five years, the Reactor Product Line has developed the integrated multi-physics code suite SHARP. The goal of developing such a tool is to perform multi-physics neutronics, thermal/fluid, and structural mechanics modeling of the components inside the full reactor core or portions of it with a user-specified fidelity. In particular SHARP contains high-fidelity single-physics codes Diablo for structural mechanics and Nek5000 for fluid mechanics calculations. Both codes are state-of-the-art, highly scalable tools that have been extensively validated. These tools form a strong basis on which to build a flow-induced vibration modeling capability. In this report we discuss one-way coupled calculations performed with Nek5000 and Diablo aimed at simulating available FIV experiments in helical steam generators in the turbulent buffeting regime. In this regime one-way coupling is judged sufficient because the pressure loads do not cause substantial displacements. It is also the most common source of vibration in helical steam generators at the low flows expected in integral PWRs. The legacy data is obtained from two datasets developed at Argonne and B&W.« less

Managing the sugar factory: A new feather in the cap for nuclear factor Y.

PubMed

Sen, Sabyasachi; Das, Chandrima

2018-05-18

Gluconeogenesis in the liver converts lipids and several other noncarbohydrate precursors into glucose, ensuring that blood sugar levels are maintained at healthy levels, especially during fasting. Effective regulation of gluconeogenesis is therefore critical for maintaining systemic metabolic homeostasis. Zhang and colleagues have discovered that the ubiquitous transcriptional regulator nuclear factor Y (NF-Y) confers cAMP responsiveness to key gluconeogenic genes and up-regulates hepatic glucose production. The study expands our understanding of transcriptional regulation of hepatic gluconeogenesis and also presents critical insights into the function of NF-Y in the liver. © 2018 Sen and Das.

Mitochondrial NUDIX hydrolases: A metabolic link between NAD catabolism, GTP and mitochondrial dynamics.

PubMed

Long, Aaron; Klimova, Nina; Kristian, Tibor

2017-10-01

NAD + catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD + catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism. Mitochondrial and cytosolic NUDIX hydrolases (NUDT9α and NUDT9β) can affect mitochondrial and cellular AMP levels by hydrolyzing ADP- ribose (ADPr) and subsequently altering the levels of GTP and ATP. Poly (ADP-ribose) polymerase 1 (PARP1) is activated after DNA damage, which depletes NAD + pools and results in the PARylation of nuclear and mitochondrial proteins. In the mitochondria, ADP-ribosyl hydrolase-3 (ARH3) hydrolyzes PAR to ADPr, while NUDT9α metabolizes ADPr to AMP. Elevated AMP levels have been reported to reduce mitochondrial ATP production by inhibiting the adenine nucleotide translocase (ANT), allosterically activating AMPK by altering the cellular AMP: ATP ratio, and by depleting mitochondrial GTP pools by being phosphorylated by adenylate kinase 3 (AK3), which uses GTP as a phosphate donor. Recently, activated AMPK was reported to phosphorylate mitochondria fission factor (MFF), which increases Drp1 localization to the mitochondria and promotes mitochondrial fission. Moreover, the increased AK3 activity could deplete mitochondrial GTP pools and possibly inhibit normal activity of GTP-dependent fusion enzymes, thus altering mitochondrial dynamics. Published by Elsevier Ltd.

Effect of electromagnetic field on cyclic adenosine monophosphate (cAMP) in a human mu-opioid receptor cell model.

PubMed

Ross, Christina L; Teli, Thaleia; Harrison, Benjamin S

2016-01-01

During the cell communication process, endogenous and exogenous signaling affect normal as well as pathological developmental conditions. Exogenous influences such as extra-low-frequency electromagnetic field (EMF) have been shown to effect pain and inflammation by modulating G-protein receptors, down-regulating cyclooxygenase-2 activity, and affecting the calcium/calmodulin/nitric oxide pathway. Investigators have reported changes in opioid receptors and second messengers, such as cyclic adenosine monophosphate (cAMP), in opiate tolerance and dependence by showing how repeated exposure to morphine decreases adenylate cyclase activity causing cAMP to return to control levels in the tolerant state, and increase above control levels during withdrawal. Resonance responses to biological systems using exogenous EMF signals suggest that frequency response characteristics of the target can determine the EMF biological response. In our past research we found significant down regulation of inflammatory markers tumor necrosis factor alpha (TNF-α) and nuclear factor kappa B (NFκB) using 5 Hz EMF frequency. In this study cAMP was stimulated in Chinese Hamster Ovary (CHO) cells transfected with human mu-opioid receptors, then exposed to 5 Hz EMF, and outcomes were compared with morphine treatment. Results showed a 23% greater inhibition of cAMP-treating cells with EMF than with morphine. In order to test our results for frequency specific effects, we ran identical experiments using 13 Hz EMF, which produced results similar to controls. This study suggests the use of EMF as a complementary or alternative treatment to morphine that could both reduce pain and enhance patient quality of life without the side-effects of opiates.

Sexual function in adolescent and young adult survivors of lower extremity bone tumors.

PubMed

Barrera, Maru; Teall, Tanya; Barr, Ronald; Silva, Mariana; Greenberg, Mark

2010-12-15

Improving survival rates and new surgical options have led to increased interest regarding late effects and quality of life in adolescent and young adult survivors of bone cancers, including their sexual functioning. This study investigated sexual functioning in adolescent and young adult survivors of lower limb bone tumors, in relation to surgical treatments, gender differences, depressive symptoms, global self worth, and physical disability. Twenty-eight participants (age range 18-32 years) completed measures of gender specific sexual function, depressive symptoms, global self worth, and physical disability. For analysis, surgical intervention was grouped into limb sparing surgeries (LS; allograft fusion and endoprosthesis) and amputation or Van Nes rotationplasty (AMP). Male survivors reported significantly higher scores than females on total sexual function scores (P = 0.050), sexual drive (P = 0.002), and frequency of sexual thoughts, fantasies or erotic dreams (P = 0.021). Men also reported significantly better physical functioning scores than women (P = 0.012). LS scored significantly lower on frequency of sexual thoughts, fantasies and erotic dreams (P = 0.048) and frequency of sexual experiences (P = 0.016) compared with AMP. In addition, LS reported significantly more depressive symptoms scores (P = 0.004) and lower self worth scores (P = 0.037), than AMP. These results suggest that male survivors of lower extremity bone tumors experience better sexual functioning than women. Survivors of limb sparing surgeries struggle with sexual function, depressive symptoms, and poor self-perception compared to Van Nes rotationplasty and amputation survivors. Copyright © 2010 Wiley-Liss, Inc.

Improvement of Pt/C/PTFE catalyst type used for hydrogen isotope separation

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

Vasut, F.; Preda, A.; Zamfirache, M.

2008-07-15

The CANDU reactor from the Nuclear Power plant Cernavoda (Romania)) is the most powerful tritium source from Europe. This reactor is moderated and cooled by heavy water that becomes continuously contaminated with tritium. Because of this reason, the National R and amp;D Inst. for Cryogenic and Isotopic Technologies developed a detritiation technology based on catalytic isotopic exchange and cryogenic distillation. The main effort of our Inst. was focused on finding more efficient catalysts with a longer operational life. Some of the tritium removal processes involved in Fusion Science and Technology use this type of catalyst 1. Several Pt/C/PTFE hydrophobic catalystsmore » that could be used in isotopic exchange process 2,3,4 were produced. The present paper presents a comparative study between the physical and morphological properties of different catalysts manufactured by impregnation at our institute. The comparison consists of a survey of specific surface, pores volume and pores distribution. (authors)« less

Dynamic modelling and parameter estimation of a hydraulic robot manipulator using a multi-objective genetic algorithm

NASA Astrophysics Data System (ADS)

Montazeri, A.; West, C.; Monk, S. D.; Taylor, C. J.

2017-04-01

This paper concerns the problem of dynamic modelling and parameter estimation for a seven degree of freedom hydraulic manipulator. The laboratory example is a dual-manipulator mobile robotic platform used for research into nuclear decommissioning. In contrast to earlier control model-orientated research using the same machine, the paper develops a nonlinear, mechanistic simulation model that can subsequently be used to investigate physically meaningful disturbances. The second contribution is to optimise the parameters of the new model, i.e. to determine reliable estimates of the physical parameters of a complex robotic arm which are not known in advance. To address the nonlinear and non-convex nature of the problem, the research relies on the multi-objectivisation of an output error single-performance index. The developed algorithm utilises a multi-objective genetic algorithm (GA) in order to find a proper solution. The performance of the model and the GA is evaluated using both simulated (i.e. with a known set of 'true' parameters) and experimental data. Both simulation and experimental results show that multi-objectivisation has improved convergence of the estimated parameters compared to the single-objective output error problem formulation. This is achieved by integrating the validation phase inside the algorithm implicitly and exploiting the inherent structure of the multi-objective GA for this specific system identification problem.

The impact of endurance exercise on global and AMPK gene-specific DNA methylation

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

King-Himmelreich, Tanya S.; Schramm, Stefanie; Wolters, Miriam C.

Alterations in gene expression as a consequence of physical exercise are frequently described. The mechanism of these regulations might depend on epigenetic changes in global or gene-specific DNA methylation levels. The AMP-activated protein kinase (AMPK) plays a key role in maintenance of energy homeostasis and is activated by increases in the AMP/ATP ratio as occurring in skeletal muscles after sporting activity. To analyze whether exercise has an impact on the methylation status of the AMPK promoter, we determined the AMPK methylation status in human blood samples from patients before and after sporting activity in the context of rehabilitation as wellmore » as in skeletal muscles of trained and untrained mice. Further, we examined long interspersed nuclear element 1 (LINE-1) as indicator of global DNA methylation changes. Our results revealed that light sporting activity in mice and humans does not alter global DNA methylation but has an effect on methylation of specific CpG sites in the AMPKα2 gene. These regulations were associated with a reduced AMPKα2 mRNA and protein expression in muscle tissue, pointing at a contribution of the methylation status to AMPK expression. Taken together, these results suggest that exercise influences AMPKα2 gene methylation in human blood and eminently in the skeletal muscle of mice and therefore might repress AMPKα2 gene expression. -- Highlights: •AMPK gene methylation increases after moderate endurance exercise in humans and mice. •AMPKα mRNA and protein decrease after moderate endurance exercise in mice. •Global DNA methylation is not affected under the same conditions.« less

Suppression of Melanin Production by Expression of HSP70*

PubMed Central

Hoshino, Tatsuya; Matsuda, Minoru; Yamashita, Yasuhiro; Takehara, Masaya; Fukuya, Masayo; Mineda, Kazutaka; Maji, Daisuke; Ihn, Hironobu; Adachi, Hiroaki; Sobue, Gen; Funasaka, Yoko; Mizushima, Tohru

2010-01-01

Skin hyperpigmentation disorders due to abnormal melanin production induced by ultraviolet (UV) irradiation are both a clinical and cosmetic problem. UV irradiation stimulates melanin production in melanocytes by increasing intracellular cAMP. Expression of heat shock proteins (HSPs), especially HSP70, is induced by various stressors, including UV irradiation, to provide cellular resistance to such stressors. In this study we examined the effect of expression of HSP70 on melanin production both in vitro and in vivo. 3-Isobutyl-1-methylxanthine (IBMX), a cAMP-elevating agent, stimulated melanin production in cultured mouse melanoma cells, and this stimulation was suppressed in cells overexpressing HSP70. IBMX-dependent transcriptional activation of the tyrosinase gene was also suppressed in HSP70-overexpressing cells. Expression of microphthalmia-associated transcription factor (MITF), which positively regulates transcription of the tyrosinase gene, was up-regulated by IBMX; however, this up-regulation was not suppressed in HSP70-overexpressing cells. On the other hand, immunoprecipitation and immunostaining analyses revealed a physical interaction between and co-localization of MITF and HSP70, respectively. Furthermore, the transcription of tyrosinase gene in nuclear extract was inhibited by HSP70. In vivo, UV irradiation of wild-type mice increased the amount of melanin in the basal layer of the epidermis, and this increase was suppressed in transgenic mice expressing HSP70. This study provides the first evidence of an inhibitory effect of HSP70 on melanin production both in vitro and in vivo. This effect seems to be mediated by modulation of MITF activity through a direct interaction between HSP70 and MITF. PMID:20177067

Hypothermia in mouse is caused by adenosine A1 and A3 receptor agonists and AMP via three distinct mechanisms.

PubMed

Carlin, Jesse Lea; Jain, Shalini; Gizewski, Elizabeth; Wan, Tina C; Tosh, Dilip K; Xiao, Cuiying; Auchampach, John A; Jacobson, Kenneth A; Gavrilova, Oksana; Reitman, Marc L

2017-03-01

Small mammals have the ability to enter torpor, a hypothermic, hypometabolic state, allowing impressive energy conservation. Administration of adenosine or adenosine 5'-monophosphate (AMP) can trigger a hypothermic, torpor-like state. We investigated the mechanisms for hypothermia using telemetric monitoring of body temperature in wild type and receptor knock out (Adora1 -/- , Adora3 -/- ) mice. Confirming prior data, stimulation of the A 3 adenosine receptor (AR) induced hypothermia via peripheral mast cell degranulation, histamine release, and activation of central histamine H 1 receptors. In contrast, A 1 AR agonists and AMP both acted centrally to cause hypothermia. Commonly used, selective A 1 AR agonists, including N 6 -cyclopentyladenosine (CPA), N 6 -cyclohexyladenosine (CHA), and MRS5474, caused hypothermia via both A 1 AR and A 3 AR when given intraperitoneally. Intracerebroventricular dosing, low peripheral doses of Cl-ENBA [(±)-5'-chloro-5'-deoxy-N 6 -endo-norbornyladenosine], or using Adora3 -/- mice allowed selective stimulation of A 1 AR. AMP-stimulated hypothermia can occur independently of A 1 AR, A 3 AR, and mast cells. A 1 AR and A 3 AR agonists and AMP cause regulated hypothermia that was characterized by a drop in total energy expenditure, physical inactivity, and preference for cooler environmental temperatures, indicating a reduced body temperature set point. Neither A 1 AR nor A 3 AR was required for fasting-induced torpor. A 1 AR and A 3 AR agonists and AMP trigger regulated hypothermia via three distinct mechanisms. Published by Elsevier Ltd.

cAMP Response Element-Binding Protein Is Required for Dopamine-Dependent Gene Expression in the Intact But Not the Dopamine-Denervated Striatum

PubMed Central

Andersson, Malin; Konradi, Christine; Cenci, M. Angela

2014-01-01

The cAMP response element-binding protein (CREB) is believed to play a pivotal role in dopamine (DA) receptor-mediated nuclear signaling and neuroplasticity. Here we demonstrate that the significance of CREB for gene expression depends on the experimental paradigm. We compared the role of CREB in two different but related models: L-DOPA administration to unilaterally 6-hydroxydopamine lesioned rats, and cocaine administration to neurologically intact animals. Antisense technology was used to produce a local knockdown of CREB in the lateral caudate–putamen, a region that mediates the dyskinetic or stereotypic manifestations associated with L-DOPA or cocaine treatment, respectively. In intact rats, CREB antisense reduced both basal and cocaine-induced expression of c-Fos, FosB/ΔFosB, and prodynorphin mRNA. In the DA-denervated striatum, CREB was not required for L-DOPA to induce these gene products, nor did CREB contribute considerably to DNA binding activity at cAMP responsive elements (CREs) and CRE-like enhancers. ΔFosB-related proteins and JunD were the main contributors to both CRE and AP-1 DNA–protein complexes in L-DOPA-treated animals. In behavioral studies, intrastriatal CREB knockdown caused enhanced activity scores in intact control animals and exacerbated the dyskinetic effects of acute L-DOPA treatment in 6-OHDA-lesioned animals. These data demonstrate that CREB is not required for the development of L-DOPA-induced dyskinesia in hemiparkinsonian rats. Moreover, our results reveal an unexpected alteration of nuclear signaling mechanisms in the parkinsonian striatum treated with L-DOPA, where AP-1 transcription factors appear to supersede CREB in the activation of CRE-containing genes. PMID:11739600

Early gene Broad complex plays a key role in regulating the immune response triggered by ecdysone in the Malpighian tubules of Drosophila melanogaster.

PubMed

Verma, Puja; Tapadia, Madhu G

2015-08-01

In insects, humoral response to injury is accomplished by the production of antimicrobial peptides (AMPs) which are secreted in the hemolymph to eliminate the pathogen. Drosophila Malpighian tubules (MTs), however, are unique immune organs that show constitutive expression of AMPs even in unchallenged conditions and the onset of immune response is developmental stage dependent. Earlier reports have shown ecdysone positively regulates immune response after pathogenic challenge however, a robust response requires prior potentiation by the hormone. Here we provide evidence to show that MTs do not require prior potentiation with ecdysone hormone for expression of AMPs and they respond to ecdysone very fast even without immune challenge, although the different AMPs Diptericin, Cecropin, Attacin, Drosocin show differential expression in response to ecdysone. We show that early gene Broad complex (BR-C) could be regulating the IMD pathway by activating Relish and physically interacting with it to activate AMPs expression. BR-C depletion from Malpighian tubules renders the flies susceptible to infection. We also show that in MTs ecdysone signaling is transduced by EcR-B1 and B2. In the absence of ecdysone signaling the IMD pathway associated genes are down regulated and activation and translocation of transcription factor Relish is also affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antimicrobial Peptides and Wound Healing: Biological and Therapeutic Considerations

PubMed Central

Mangoni, Maria Luisa; McDermott, Alison M.; Zasloff, Michael

2016-01-01

Repair of tissue wounds is a fundamental process to re-establish tissue integrity and regular function. Importantly, infection is a major factor that hinders wound healing. Multicellular organisms have evolved an arsenal of host-defence molecules, including antimicrobial peptides (AMPs), aimed at controlling microbial proliferation and at modulating the host's immune response to a variety of biological or physical insults. In this brief review we provide the evidence for a role of AMPs as endogenous mediators of wound healing and their promising therapeutic potential for treatment of non-life threatening skin and other epithelial injuries. PMID:26738772

Bridging simulations and experiment in shock and ramp induced phenomena

NASA Astrophysics Data System (ADS)

Flicker, Dawn

2014-03-01

The high pressure materials physics program at Sandia's Z facility includes strong collaboration between theory, simulations and experiments. This multi-disciplinary approach has led to new insights in many cases. Several examples will be discussed to illustrate the benefits of bridging simulations and experiments. Results will be chosen from recent work on the xenon equation of state, phase change in MgO, shock induced chemistry in CO2 and tantalum strength. Sandia National Laboratories is a multi-program laboratory operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Radiation Physics for Space and High Altitude Air Travel

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Wilson, J. W.; Goldhagen, P.; Saganti, P.; Shavers, M. R.; McKay, Gordon A. (Technical Monitor)

2000-01-01

Galactic cosmic rays (GCR) are of extra-solar origin consisting of high-energy hydrogen, helium, and heavy ions. The GCR are modified by physical processes as they traverse through the solar system, spacecraft shielding, atmospheres, and tissues producing copious amounts of secondary radiation including fragmentation products, neutrons, mesons, and muons. We discuss physical models and measurements relevant for estimating biological risks in space and high-altitude air travel. Ambient and internal spacecraft computational models for the International Space Station and a Mars mission are discussed. Risk assessment is traditionally based on linear addition of components. We discuss alternative models that include stochastic treatments of columnar damage by heavy ion tracks and multi-cellular damage following nuclear fragmentation in tissue.

Deployment of the National Transparent Optical Network around the San Francisco Bay Area

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

McCammon, K.; Haigh, R.; Armstrong, G.

1996-06-01

We report on the deployment and initial operation of the National Transparent Optical Network, an experimental WDM network testbed around the San Francisco Bay Area, during the Optical Fiber Conference (OFC`96) held in San Jose, CA. The deployment aspects of the physical plant, optical and SONET layers are examined along with a discussion of broadband applications which utilized the network during the OFC`96 demonstration. The network features dense WDM technology, transparent optical routing technology using acousto- optic tunable filter based switches, and network modules with add/drop, multicast, and wavelength translation capabilities. The physical layer consisted of over 300 km ofmore » Sprint and Pacific Bell conventional single mode fiber which was amplified with I I optical amplifiers deployed in pre-amp, post-amp, and line amp configurations. An out-of-band control network provided datacom channels from remote equipment sites to the SONET network manager deployed at the San Jose Convention Center for the conference. Data transport over five wavelengths was achieved in the 1550 nm window using a variety of signal formats including analog and digital signal transmission on different wavelengths on the same fiber. The network operated throughout the week of OFC`96 and is still in operation today.« less

Comparisons of Spectral Aerosol Single Scattering Albedo in Seoul, South Korea

NASA Technical Reports Server (NTRS)

Mok, Jungbin; Krotkov, Nickolay A.; Torres, Omar; Jethva, Hiren; Loughman, Robert P.; Spinei, Elena; Campanelli, Monica; Li, Zhanqing; Go, Sujung; Labow, Gordon;

The nuclear question: rethinking species importance in multi-species animal groups.

PubMed

Srinivasan, Umesh; Raza, Rashid Hasnain; Quader, Suhel

2010-09-01

1. Animals group for various benefits, and may form either simple single-species groups, or more complex multi-species associations. Multi-species groups are thought to provide anti-predator and foraging benefits to participant individuals. 2. Despite detailed studies on multi-species animal groups, the importance of species in group initiation and maintenance is still rated qualitatively as 'nuclear' (maintaining groups) or 'attendant' (species following nuclear species) based on species-specific traits. This overly simplifies and limits understanding of inherently complex associations, and is biologically unrealistic, because species roles in multi-species groups are: (i) likely to be context-specific and not simply a fixed species property, and (ii) much more variable than this dichotomy indicates. 3. We propose a new view of species importance (measured as number of inter-species associations), along a continuum from 'most nuclear' to 'least nuclear'. Using mixed-species bird flocks from a tropical rainforest in India as an example, we derive inter-species association measures from randomizations on bird species abundance data (which takes into account species 'availability') and data on 86 mixed-species flocks from two different flock types. Our results show that the number and average strength of inter-species associations covary positively, and we argue that species with many, strong associations are the most nuclear. 4. From our data, group size and foraging method are ecological and behavioural traits of species that best explain nuclearity in mixed-species bird flocks. Parallels have been observed in multi-species fish shoals, in which group size and foraging method, as well as diet, have been shown to correlate with nuclearity. Further, the context in which multi-species groups occur, in conjunction with species-specific traits, influences the role played by a species in a multi-species group, and this highlights the importance of extrinsic factors in shaping species importance. 5. Our view of nuclearity provides predictive power in examining species roles in a variety of situations (e.g. predicting leadership in differently composed communities), and can be applied to examine a broad range of ecological and evolutionary questions pertinent to multi-species groups in general.

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

PubMed

Rivas-Santiago, Bruno; Torres-Juarez, Flor

2018-03-27

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of world health organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the antimicrobial peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Regulatory actions of 3',5'-cyclic adenosine monophosphate on osteoclast function: possible roles of Epac-mediated signaling.

PubMed

Jeevaratnam, Kamalan; Salvage, Samantha C; Li, Mengye; Huang, Christopher L-H

2018-05-30

Alterations in cellular levels of the second messenger 3',5'-cyclic adenosine monophosphate ([cAMP] i ) regulate a wide range of physiologically important cellular signaling processes in numerous cell types. Osteoclasts are terminally differentiated, multinucleated cells specialized for bone resorption. Their systemic regulator, calcitonin, triggers morphometrically and pharmacologically distinct retraction (R) and quiescence (Q) effects on cell-spread area and protrusion-retraction motility, respectively, paralleling its inhibition of bone resorption. Q effects were reproduced by cholera toxin-mediated G s -protein activation known to increase [cAMP] i , unaccompanied by the [Ca 2+ ] i changes contrastingly associated with R effects. We explore a hypothesis implicating cAMP signaling involving guanine nucleotide-exchange activation of the small GTPase Ras-proximate-1 (Rap1) by exchange proteins directly activated by cAMP (Epac). Rap1 activates integrin clustering, cell adhesion to bone matrix, associated cytoskeletal modifications and signaling processes, and transmembrane transduction functions. Epac activation enhanced, whereas Epac inhibition or shRNA-mediated knockdown compromised, the appearance of markers for osteoclast differentiation and motility following stimulation by receptor activator of nuclear factor kappa-Β ligand (RANKL). Deficiencies in talin and Rap1 compromised in vivo bone resorption, producing osteopetrotic phenotypes in genetically modified murine models. Translational implications of an Epac-Rap1 signaling hypothesis in relationship to N-bisphosphonate actions on prenylation and membrane localization of small GTPases are discussed. © 2018 New York Academy of Sciences.

Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an in vitro reperfusion model

PubMed Central

Takuma, K; Lee, E; Enomoto, R; Mori, K; Baba, A; Matsuda, T

2001-01-01

We examined the effect of 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (ibudilast), which has been clinically used for bronchial asthma and cerebrovascular disorders, on cell viability induced in a model of reperfusion injury. Ibudilast at 10 – 100 μM significantly attenuated the H2O2-induced decrease in cell viability. Ibudilast inhibited the H2O2-induced cytochrome c release, caspase-3 activation, DNA ladder formation and nuclear condensation, suggesting its anti-apoptotic effect. Phosphodiesterase inhibitors such as theophylline, pentoxyfylline, vinpocetine, dipyridamole and zaprinast, which increased the guanosine-3′,5′-cyclic monophosphate (cyclic GMP) level, and dibutyryl cyclic GMP attenuated the H2O2-induced injury in astrocytes. Ibudilast increased the cyclic GMP level in astrocytes. The cyclic GMP-dependent protein kinase inhibitor KT5823 blocked the protective effects of ibudilast and dipyridamole on the H2O2-induced decrease in cell viability, while the cyclic AMP-dependent protein kinase inhibitor KT5720, the cyclic AMP antagonist Rp-cyclic AMPS, the mitogen-activated protein/extracellular signal-regulated kinase inhibitor PD98059 and the leukotriene D4 antagonist LY 171883 did not. KT5823 also blocked the effect of ibudilast on the H2O2-induced cytochrome c release and caspase-3-like protease activation. These findings suggest that ibudilast prevents the H2O2-induced delayed apoptosis of astrocytes via a cyclic GMP, but not cyclic AMP, signalling pathway. PMID:11454657

Chlorogenic acid ameliorates endotoxin-induced liver injury by promoting mitochondrial oxidative phosphorylation.

PubMed

Zhou, Yan; Ruan, Zheng; Zhou, Lili; Shu, Xugang; Sun, Xiaohong; Mi, Shumei; Yang, Yuhui; Yin, Yulong

2016-01-22

Acute or chronic hepatic injury is a common pathology worldwide. Mitochondrial dysfunction and the depletion of adenosine triphosphate (ATP) play important roles in liver injury. Chlorogenic acids (CGA) are some of the most abundant phenolic acids in human diet. This study was designed to test the hypothesis that CGA may protect against chronic lipopolysaccharide (LPS)-induced liver injury by modulating mitochondrial energy generation. CGA decreased the activities of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. The contents of ATP and adenosine monophosphate (AMP), as well as the ratio of AMP/ATP, were increased after CGA supplementation. The activities of enzymes that are involved in glycolysis were reduced, while those of enzymes involved in oxidative phosphorylation were increased. Moreover, phosphorylated AMP-activated protein kinase (AMPK), and mRNA levels of AMPK-α, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial DNA transcription factor A were increased after CGA supplementation. Collectively, these findings suggest that the hepatoprotective effect of CGA might be associated with enhanced ATP production, the stimulation of mitochondrial oxidative phosphorylation and the inhibition of glycolysis. Copyright © 2015 Elsevier Inc. All rights reserved.

DISC1, PDE4B, and NDE1 at the centrosome and synapse

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

Bradshaw, Nicholas J.; Ogawa, Fumiaki; Antolin-Fontes, Beatriz

Disrupted-In-Schizophrenia 1 (DISC1) is a risk factor for schizophrenia and other major mental illnesses. Its protein binding partners include the Nuclear Distribution Factor E Homologs (NDE1 and NDEL1), LIS1, and phosphodiesterases 4B and 4D (PDE4B and PDE4D). We demonstrate that NDE1, NDEL1 and LIS1, together with their binding partner dynein, associate with DISC1, PDE4B and PDE4D within the cell, and provide evidence that this complex is present at the centrosome. LIS1 and NDEL1 have been previously suggested to be synaptic, and we now demonstrate localisation of DISC1, NDE1, and PDE4B at synapses in cultured neurons. NDE1 is phosphorylated by cAMP-dependantmore » Protein Kinase A (PKA), whose activity is, in turn, regulated by the cAMP hydrolysis activity of phosphodiesterases, including PDE4. We propose that DISC1 acts as an assembly scaffold for all of these proteins and that the NDE1/NDEL1/LIS1/dynein complex is modulated by cAMP levels via PKA and PDE4.« less

Deficient Gene Expression in Protein Kinase Inhibitor α Null Mutant Mice

PubMed Central

Gangolli, Esha A.; Belyamani, Mouna; Muchinsky, Sara; Narula, Anita; Burton, Kimberly A.; McKnight, G. Stanley; Uhler, Michael D.; Idzerda, Rejean L.

2000-01-01

Protein kinase inhibitor (PKI) is a potent endogenous inhibitor of the cyclic AMP (cAMP)-dependent protein kinase (PKA). It functions by binding the free catalytic (C) subunit with a high affinity and is also known to export nuclear C subunit to the cytoplasm. The significance of these actions with respect to PKI's physiological role is not well understood. To address this, we have generated by homologous recombination mutant mice that are deficient in PKIα, one of the three isoforms of PKI. The mice completely lack PKI activity in skeletal muscle and, surprisingly, show decreased basal and isoproterenol-induced gene expression in muscle. Further examination revealed reduced levels of the phosphorylated (active) form of the transcription factor CREB (cAMP response element binding protein) in the knockouts. This phenomenon stems, at least in part, from lower basal PKA activity levels in the mutants, arising from a compensatory increase in the level of the RIα subunit of PKA. The deficit in gene induction, however, is not easily explained by current models of PKI function and suggests that PKI may play an as yet undescribed role in PKA signaling. PMID:10779334

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

Hamilton, T.; Jones, H.; Wong, K.

The Marshall Islands Environmental Characterization and Dose Assessment Program has recently implemented waste minimization measures to reduce low level radioactive (LLW) and low level mixed (LLWMIXED) waste streams at the Lawrence Livermore National Laboratory (LLNL). Several thousand environmental samples are collected annually from former US nuclear test sites in the Marshall Islands, and returned to LLNL for processing and radiometric analysis. In the past, we analyzed coconut milk directly by gamma-spectrometry after adding formaldehyde (as preservative) and sealing the fluid in metal cans. This procedure was not only tedious and time consuming but generated storage and waste disposal problems. Wemore » have now reduced the number of coconut milk samples required for analysis from 1500 per year to approximately 250, and developed a new analytical procedure which essentially eliminates the associated mixed radioactive waste stream. Coconut milk samples are mixed with a few grams of ammonium-molydophosphate (AMP) which quantitatively scavenges the target radionuclide cesium 137 in an ion-exchange process. The AMP is then separated from the mixture and sealed in a plastic container. The bulk sample material can be disposed of as a non- radioactive non-hazardous waste, and the relatively small amount of AMP conveniently counted by gamma-spectrometry, packaged and stored for future use.« less

Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase.

PubMed

Zheng, D; MacLean, P S; Pohnert, S C; Knight, J B; Olson, A L; Winder, W W; Dohm, G L

2001-09-01

Skeletal muscle GLUT-4 transcription in response to treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), a known activator of AMP-activated protein kinase (AMPK), was studied in rats and mice. The increase in GLUT-4 mRNA levels in response to a single subcutaneous injection of AICAR, peaked at 13 h in white and red quadriceps muscles but not in the soleus muscle. The mRNA level of chloramphenicol acyltransferase reporter gene which is driven by 1,154 or 895 bp of the human GLUT-4 proximal promoter was increased in AICAR-treated transgenic mice, demonstrating the transcriptional upregulation of the GLUT-4 gene by AICAR. However, this induction of transcription was not apparent with 730 bp of the promoter. In addition, nuclear extracts from AICAR-treated mice bound to the consensus sequence of myocyte enhancer factor-2 (from -473 to -464) to a greater extent than from saline-injected mice. Thus AMP-activated protein kinase activation by AICAR increases GLUT-4 transcription by a mechanism that requires response elements within 895 bp of human GLUT-4 proximal promoter and that may be cooperatively mediated by myocyte enhancer factor-2.

Prospects for the study of the properties of dense nuclear matter at the NICA heavy-ion complex at JINR (Dubna)

NASA Astrophysics Data System (ADS)

Kolesnikov, V. I.

2017-06-01

The NICA (Nuclotron-based Ion Collider fAcility) project is aimed in the construction at JINR (Dubna) a modern accelerator complex equipped with three detectors: the MultiPurpose Detector (MPD) and the Spin Physics Detector (SPD) at the NICA collider, as well as a fixed target experiment BM&N which will be use extracted beams from the Nuclotron accelerator. In this report, an overview of the main physics objectives of the NICA heavy-ion program will be given and the recent progress in the NICA construction (both accelerator complex and detectors) will be described.

Multiple detector focal plane array ultraviolet spectrometer for the AMPS laboratory

NASA Technical Reports Server (NTRS)

Feldman, P. D.

1975-01-01

The possibility of meeting the requirements of the amps spectroscopic instrumentation by using a multi-element focal plane detector array in a conventional spectrograph mount was examined. The requirements of the detector array were determined from the optical design of the spectrometer which in turn depends on the desired level of resolution and sensitivity required. The choice of available detectors and their associated electronics and controls was surveyed, bearing in mind that the data collection rate from this system is so great that on-board processing and reduction of data are absolutely essential. Finally, parallel developments in instrumentation for imaging in astronomy were examined, both in the ultraviolet (for the Large Space Telescope as well as other rocket and satellite programs) and in the visible, to determine what progress in that area can have direct bearing on atmospheric spectroscopy.

Binary Colloidal Crystal Layers as Platforms for Surface Patterning of Puroindoline-Based Antimicrobial Peptides.

PubMed

Boden, Andrew; Bhave, Mrinal; Wang, Peng-Yuan; Jadhav, Snehal; Kingshott, Peter

2018-01-24

The ability of bacteria to form biofilms and the emergence of antibiotic-resistant strains have prompted the need to develop the next generation of antibacterial coatings. Antimicrobial peptides (AMPs) are showing promise as molecules that can address these issues, especially if used when immobilized as a surface coating. We present a method that explores how surface patterns together with the selective immobilization of an AMP called PuroA (FPVTWRWWKWWKG-NH 2 ) can be used to both kill bacteria and also as a tool to study bacterial attachment mechanisms. Surface patterning is achieved using stabilized self-assembled binary colloidal crystal (BCC) layers, allowing selective PuroA immobilization to carboxylated particles using N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide (EDC) hydrochloride/N-hydroxysuccinimide (NHS) coupling chemistry. Covalent immobilization of PuroA was compared with physical adsorption (i.e., without the addition of EDC/NHS). The AMP-functionalized colloids and BCC layers were characterized by X-ray photoelectron spectroscopy, ζ potentials, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Surface antimicrobial activity was assessed by viability assays using Escherichia coli. MALDI-TOF MS analysis revealed that although not all of PuroA was successfully covalently immobilized, a relatively low density of PuroA (1.93 × 10 13 molecules/cm 2 and 7.14 × 10 12 molecules/cm 2 for covalent and physical immobilization, respectively) was found to be sufficient at significantly decreasing the viability of E. coli by 70% when compared to that of control samples. The findings provide a proof of concept that BCC layers are a suitable platform for the patterned immobilization of AMPs and the importance of ascertaining the success of small-molecule grafting reactions using surface-MALDI, something that is often assumed to be successful in the field.

FPGA-based multi-channel fluorescence lifetime analysis of Fourier multiplexed frequency-sweeping lifetime imaging

PubMed Central

Zhao, Ming; Li, Yu; Peng, Leilei

2014-01-01

We report a fast non-iterative lifetime data analysis method for the Fourier multiplexed frequency-sweeping confocal FLIM (Fm-FLIM) system [ Opt. Express22, 10221 ( 2014)24921725]. The new method, named R-method, allows fast multi-channel lifetime image analysis in the system’s FPGA data processing board. Experimental tests proved that the performance of the R-method is equivalent to that of single-exponential iterative fitting, and its sensitivity is well suited for time-lapse FLIM-FRET imaging of live cells, for example cyclic adenosine monophosphate (cAMP) level imaging with GFP-Epac-mCherry sensors. With the R-method and its FPGA implementation, multi-channel lifetime images can now be generated in real time on the multi-channel frequency-sweeping FLIM system, and live readout of FRET sensors can be performed during time-lapse imaging. PMID:25321778

Regulation of insulin-like growth factor I transcription by cyclic adenosine 3',5'-monophosphate (cAMP) in fetal rat bone cells through an element within exon 1: protein kinase A-dependent control without a consensus AMP response element

NASA Technical Reports Server (NTRS)

McCarthy, T. L.; Thomas, M. J.; Centrella, M.; Rotwein, P.

1995-01-01

Insulin-like growth factor I (IGF-I) is a locally synthesized anabolic growth factor for bone. IGF-I synthesis by primary fetal rat osteoblasts (Ob) is stimulated by agents that increase the intracellular cAMP concentration, including prostaglandin E2 (PGE2). Previous studies with Ob cultures demonstrated that PGE2 enhanced IGF-I transcription through selective use of IGF-I promoter 1, with little effect on IGF-I messenger RNA half-life. Transient transfection of Ob cultures with an array of promoter 1-luciferase reporter fusion constructs has now allowed localization of a potential cis-acting promoter element(s) responsible for cAMP-stimulated gene expression to the 5'-untranslated region (5'-UTR) of IGF-I exon 1, within a segment lacking a consensus cAMP response element. Our evidence derives from three principal observations: 1) a transfection construct containing only 122 nucleotides (nt) of promoter 1 and 328 nt of the 5'-UTR retained full PGE2-stimulated reporter expression; 2) maximal PGE2-driven reporter expression required the presence of nt 196 to 328 of exon 1 when tested within the context of IGF-I promoter 1; 3) cotransfection of IGF-I promoter-luciferase-reporter constructs with a plasmid encoding the alpha-isoform of the catalytic subunit of murine cAMP-dependent protein kinase (PKA) produced results comparable to those seen with PGE2 treatment, whereas cotransfection with a plasmid encoding a mutant regulatory subunit of PKA that cannot bind cAMP blocked PGE2-induced reporter expression. Deoxyribonuclease I footprinting of the 5'-UTR of exon 1 demonstrated protected sequences at HS3A, HS3B, and HS3D, three of six DNA-protein binding sites previously characterized with rat liver nuclear extracts. Of these three regions, only the HS3D binding site is located within the functionally identified hormonally responsive segment of IGF-I exon 1. These results directly implicate PKA in the control of IGF-I gene transcription by PGE2 and identify a segment of IGF-I exon 1 as being essential for this hormonal regulation.

Exploring encapsulation mechanism of DNA and mononucleotides in sol-gel derived silica.

PubMed

Kapusuz, Derya; Durucan, Caner

2017-07-01

The encapsulation mechanism of DNA in sol-gel derived silica has been explored in order to elucidate the effect of DNA conformation on encapsulation and to identify the nature of chemical/physical interaction of DNA with silica during and after sol-gel transition. In this respect, double stranded DNA and dAMP (2'-deoxyadenosine 5'-monophosphate) were encapsulated in silica using an alkoxide-based sol-gel route. Biomolecule-encapsulating gels have been characterized using UV-Vis, 29 Si NMR, FTIR spectroscopy and gas adsorption (BET) to investigate chemical interactions of biomolecules with the porous silica network and to examine the extent of sol-gel reactions upon encapsulation. Ethidium bromide intercalation and leach out tests showed that helix conformation of DNA was preserved after encapsulation. For both biomolecules, high water-to-alkoxide ratio promoted water-producing condensation and prevented alcoholic denaturation. NMR and FTIR analyses confirmed high hydraulic reactivity (water adsorption) for more silanol groups-containing DNA and dAMP encapsulated gels than plain silica gel. No chemical binding/interaction occurred between biomolecules and silica network. DNA and dAMP encapsulated silica gelled faster than plain silica due to basic nature of DNA or dAMP containing buffer solutions. DNA was not released from silica gels to aqueous environment up to 9 days. The chemical association between DNA/dAMP and silica host was through phosphate groups and molecular water attached to silanols, acting as a barrier around biomolecules. The helix morphology was found not to be essential for such interaction. BET analyses showed that interconnected, inkbottle-shaped mesoporous silica network was condensed around DNA and dAMP molecules.

Commissioning and Plans for the NSTX-U Facility

NASA Astrophysics Data System (ADS)

Ono, Masayuki; NSTX-U Team

2016-10-01

The National Spherical Torus Experiment - Upgrade (NSTX-U) has started its first year of plasma operations after the successful completion of the CD-4 milestones. The unique operating regimes of NSTX-U can contribute to several important issues in the physics of burning plasmas to optimize the performance of ITER. The major mission of NSTX-U is also to develop the physics and technology basis for an ST-based Fusion Nuclear Science Facility (FNSF). The new center stack will provide toroidal field of 1 Tesla at a major radius of 0.93 m which should enable a plasma current of up to 2 mega-Amp for 5 sec. A much more tangential 2nd NBI system, with 2-3 times higher current drive efficiency compared to the 1st NBI system, is installed. NSTX-U is designed to attain the 100% non-inductive operation needed for a compact FNSF design. With higher fields and heating powers of 14 MW, the NSTX-U plasma collisionality will be reduced by a factor of 3-6 to help explore the trend in transport towards the low collisionality FNSF regime. If the favorable trends observed on NSTX holds at low collisionality, high fusion neutron fluences could be achievable in very compact ST devices.

The Lifecycle of Bayesian Network Models Developed for Multi-Source Signature Assessment of Nuclear Programs

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

Gastelum, Zoe N.; White, Amanda M.; Whitney, Paul D.

2013-06-04

The Multi-Source Signatures for Nuclear Programs project, part of Pacific Northwest National Laboratory’s (PNNL) Signature Discovery Initiative, seeks to computationally capture expert assessment of multi-type information such as text, sensor output, imagery, or audio/video files, to assess nuclear activities through a series of Bayesian network (BN) models. These models incorporate knowledge from a diverse range of information sources in order to help assess a country’s nuclear activities. The models span engineering topic areas, state-level indicators, and facility-specific characteristics. To illustrate the development, calibration, and use of BN models for multi-source assessment, we present a model that predicts a country’s likelihoodmore » to participate in the international nuclear nonproliferation regime. We validate this model by examining the extent to which the model assists non-experts arrive at conclusions similar to those provided by nuclear proliferation experts. We also describe the PNNL-developed software used throughout the lifecycle of the Bayesian network model development.« less

Developing Discontinuous Galerkin Methods for Solving Multiphysics Problems in General Relativity

NASA Astrophysics Data System (ADS)

Kidder, Lawrence; Field, Scott; Teukolsky, Saul; Foucart, Francois; SXS Collaboration

2016-03-01

Multi-messenger observations of the merger of black hole-neutron star and neutron star-neutron star binaries, and of supernova explosions will probe fundamental physics inaccessible to terrestrial experiments. Modeling these systems requires a relativistic treatment of hydrodynamics, including magnetic fields, as well as neutrino transport and nuclear reactions. The accuracy, efficiency, and robustness of current codes that treat all of these problems is not sufficient to keep up with the observational needs. We are building a new numerical code that uses the Discontinuous Galerkin method with a task-based parallelization strategy, a promising combination that will allow multiphysics applications to be treated both accurately and efficiently on petascale and exascale machines. The code will scale to more than 100,000 cores for efficient exploration of the parameter space of potential sources and allowed physics, and the high-fidelity predictions needed to realize the promise of multi-messenger astronomy. I will discuss the current status of the development of this new code.

Development of computer-based analytical tool for assessing physical protection system

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

Mardhi, Alim, E-mail: alim-m@batan.go.id; Chulalongkorn University, Faculty of Engineering, Nuclear Engineering Department, 254 Phayathai Road, Pathumwan, Bangkok Thailand. 10330; Pengvanich, Phongphaeth, E-mail: ppengvan@gmail.com

Assessment of physical protection system effectiveness is the priority for ensuring the optimum protection caused by unlawful acts against a nuclear facility, such as unauthorized removal of nuclear materials and sabotage of the facility itself. Since an assessment based on real exercise scenarios is costly and time-consuming, the computer-based analytical tool can offer the solution for approaching the likelihood threat scenario. There are several currently available tools that can be used instantly such as EASI and SAPE, however for our research purpose it is more suitable to have the tool that can be customized and enhanced further. In this work,more » we have developed a computer–based analytical tool by utilizing the network methodological approach for modelling the adversary paths. The inputs are multi-elements in security used for evaluate the effectiveness of the system’s detection, delay, and response. The tool has capability to analyze the most critical path and quantify the probability of effectiveness of the system as performance measure.« less

Development of computer-based analytical tool for assessing physical protection system

NASA Astrophysics Data System (ADS)

Mardhi, Alim; Pengvanich, Phongphaeth

2016-01-01

Assessment of physical protection system effectiveness is the priority for ensuring the optimum protection caused by unlawful acts against a nuclear facility, such as unauthorized removal of nuclear materials and sabotage of the facility itself. Since an assessment based on real exercise scenarios is costly and time-consuming, the computer-based analytical tool can offer the solution for approaching the likelihood threat scenario. There are several currently available tools that can be used instantly such as EASI and SAPE, however for our research purpose it is more suitable to have the tool that can be customized and enhanced further. In this work, we have developed a computer-based analytical tool by utilizing the network methodological approach for modelling the adversary paths. The inputs are multi-elements in security used for evaluate the effectiveness of the system's detection, delay, and response. The tool has capability to analyze the most critical path and quantify the probability of effectiveness of the system as performance measure.

Progress on China nuclear data processing code system

NASA Astrophysics Data System (ADS)

Liu, Ping; Wu, Xiaofei; Ge, Zhigang; Li, Songyang; Wu, Haicheng; Wen, Lili; Wang, Wenming; Zhang, Huanyu

2017-09-01

China is developing the nuclear data processing code Ruler, which can be used for producing multi-group cross sections and related quantities from evaluated nuclear data in the ENDF format [1]. The Ruler includes modules for reconstructing cross sections in all energy range, generating Doppler-broadened cross sections for given temperature, producing effective self-shielded cross sections in unresolved energy range, calculating scattering cross sections in thermal energy range, generating group cross sections and matrices, preparing WIMS-D format data files for the reactor physics code WIMS-D [2]. Programming language of the Ruler is Fortran-90. The Ruler is tested for 32-bit computers with Windows-XP and Linux operating systems. The verification of Ruler has been performed by comparison with calculation results obtained by the NJOY99 [3] processing code. The validation of Ruler has been performed by using WIMSD5B code.

Bacterial effector binds host cell adenylyl cyclase to potentiate Gαs-dependent cAMP production

PubMed Central

Pulliainen, Arto T.; Pieles, Kathrin; Brand, Cameron S.; Hauert, Barbara; Böhm, Alex; Quebatte, Maxime; Wepf, Alexander; Gstaiger, Matthias; Aebersold, Ruedi; Dessauer, Carmen W.; Dehio, Christoph

2012-01-01

Subversion of host organism cAMP signaling is an efficient and widespread mechanism of microbial pathogenesis. Bartonella effector protein A (BepA) of vasculotumorigenic Bartonella henselae protects the infected human endothelial cells against apoptotic stimuli by elevation of cellular cAMP levels by an as yet unknown mechanism. Here, adenylyl cyclase (AC) and the α-subunit of the AC-stimulating G protein (Gαs) were identified as potential cellular target proteins for BepA by gel-free proteomics. Results of the proteomics screen were evaluated for physical and functional interaction by: (i) a heterologous in vivo coexpression system, where human AC activity was reconstituted under the regulation of Gαs and BepA in Escherichia coli; (ii) in vitro AC assays with membrane-anchored full-length human AC and recombinant BepA and Gαs; (iii) surface plasmon resonance experiments; and (iv) an in vivo fluorescence bimolecular complementation-analysis. The data demonstrate that BepA directly binds host cell AC to potentiate the Gαs-dependent cAMP production. As opposed to the known microbial mechanisms, such as ADP ribosylation of G protein α-subunits by cholera and pertussis toxins, the fundamentally different BepA-mediated elevation of host cell cAMP concentration appears subtle and is dependent on the stimulus of a G protein-coupled receptor-released Gαs. We propose that this mechanism contributes to the persistence of Bartonella henselae in the chronically infected vascular endothelium. PMID:22635269

Induction of cyclooxygenase-2 by ginsenoside Rd via activation of CCAAT-enhancer binding proteins and cyclic AMP response binding protein

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

Jeong, Hye Gwang; Pokharel, Yuba Raj; Han, Eun Hee

2007-07-20

Panax ginseng is a widely used herbal medicine in East Asia and is reported to have a variety of pharmacological effects against cardiovascular diseases and cancers. Here we show a unique effect of ginsenoside Rd (Rd) on cyclooxygenase-2 (COX-2) expression in RAW264.7 macrophages. Rd (100 {mu}g/ml), but not other ginsenosides induced COX-2 and increased prostaglandin E{sub 2} production. Gel shift and Western blot analyses using nuclear fractions revealed that Rd increased both the DNA binding of and the nuclear levels of CCAAT/enhancer binding protein (C/EBP){alpha}/{beta} and cyclic AMP response element binding protein (CREB), but not of p65, in RAW264.7 cells.more » Moreover, Rd increased the luciferase reporter gene activity in cells transfected with a 574-bp mouse COX-2 promoter construct. Site-specific mutation analyses confirmed that Rd-mediated transcriptional activation of COX-2 gene was regulated by C/EBP and CREB. These results provide evidence that Rd activated C/EBP and CREB, and that the activation of C/EBP and CREB appears to be essential for induction of COX-2 in RAW264.7 cells.« less

Intermediate energy heavy ions: An emerging multi-disciplinary research tool

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

Alonso, J.R.

1988-10-01

In the ten years that beams of intermediate energy ({approx}50 MeV/amu{le}E{le}{approx}2 GeV/amu) heavy ions (Z{le}92) have been available, an increasing number of new research areas have been opened up. Pioneering work at the Bevalac at the Lawrence Berkeley Laboratory, still the world's only source of the heaviest beams in this energy range, has led to the establishment of active programs in nuclear physics, atomic physics, cosmic ray physics, as well as biology and medicine, and industrial applications. The great promise for growth of these research areas has led to serious planning for new facilities capable of delivering such beams; severalmore » such facilities are now in construction around the world. 20 refs., 5 figs., 1 tab.« less

Matrix theory for baryons: an overview of holographic QCD for nuclear physics.

PubMed

Aoki, Sinya; Hashimoto, Koji; Iizuka, Norihiro

2013-10-01

We provide, for non-experts, a brief overview of holographic QCD (quantum chromodynamics) and a review of the recent proposal (Hashimoto et al 2010 (arXiv:1003.4988[hep-th])) of a matrix-like description of multi-baryon systems in holographic QCD. Based on the matrix model, we derive the baryon interaction at short distances in multi-flavor holographic QCD. We show that there is a very universal repulsive core of inter-baryon forces for a generic number of flavors. This is consistent with a recent lattice QCD analysis for Nf = 2, 3 where the repulsive core looks universal. We also provide a comparison of our results with the lattice QCD and the operator product expansion analysis.

Computer-aided design of multi-target ligands at A1R, A2AR and PDE10A, key proteins in neurodegenerative diseases.

PubMed

Kalash, Leen; Val, Cristina; Azuaje, Jhonny; Loza, María I; Svensson, Fredrik; Zoufir, Azedine; Mervin, Lewis; Ladds, Graham; Brea, José; Glen, Robert; Sotelo, Eddy; Bender, Andreas

2017-12-30

Compounds designed to display polypharmacology may have utility in treating complex diseases, where activity at multiple targets is required to produce a clinical effect. In particular, suitable compounds may be useful in treating neurodegenerative diseases by promoting neuronal survival in a synergistic manner via their multi-target activity at the adenosine A 1 and A 2A receptors (A 1 R and A 2A R) and phosphodiesterase 10A (PDE10A), which modulate intracellular cAMP levels. Hence, in this work we describe a computational method for the design of synthetically feasible ligands that bind to A 1 and A 2A receptors and inhibit phosphodiesterase 10A (PDE10A), involving a retrosynthetic approach employing in silico target prediction and docking, which may be generally applicable to multi-target compound design at several target classes. This approach has identified 2-aminopyridine-3-carbonitriles as the first multi-target ligands at A 1 R, A 2A R and PDE10A, by showing agreement between the ligand and structure based predictions at these targets. The series were synthesized via an efficient one-pot scheme and validated pharmacologically as A 1 R/A 2A R-PDE10A ligands, with IC 50 values of 2.4-10.0 μM at PDE10A and K i values of 34-294 nM at A 1 R and/or A 2A R. Furthermore, selectivity profiling of the synthesized 2-amino-pyridin-3-carbonitriles against other subtypes of both protein families showed that the multi-target ligand 8 exhibited a minimum of twofold selectivity over all tested off-targets. In addition, both compounds 8 and 16 exhibited the desired multi-target profile, which could be considered for further functional efficacy assessment, analog modification for the improvement of selectivity towards A 1 R, A 2A R and PDE10A collectively, and evaluation of their potential synergy in modulating cAMP levels.

Numerical Simulations of Single Flow Element in a Nuclear Thermal Thrust Chamber

NASA Technical Reports Server (NTRS)

Cheng, Gary; Ito, Yasushi; Ross, Doug; Chen, Yen-Sen; Wang, Ten-See

2007-01-01

The objective of this effort is to develop an efficient and accurate computational methodology to predict both detailed and global thermo-fluid environments of a single now element in a hypothetical solid-core nuclear thermal thrust chamber assembly, Several numerical and multi-physics thermo-fluid models, such as chemical reactions, turbulence, conjugate heat transfer, porosity, and power generation, were incorporated into an unstructured-grid, pressure-based computational fluid dynamics solver. The numerical simulations of a single now element provide a detailed thermo-fluid environment for thermal stress estimation and insight for possible occurrence of mid-section corrosion. In addition, detailed conjugate heat transfer simulations were employed to develop the porosity models for efficient pressure drop and thermal load calculations.

Multi-Group Formulation of the Temperature-Dependent Resonance Scattering Model and its Impact on Reactor Core Parameters

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

Ghrayeb, Shadi Z.; Ougouag, Abderrafi M.; Ouisloumen, Mohamed

2014-01-01

A multi-group formulation for the exact neutron elastic scattering kernel is developed. It incorporates the neutron up-scattering effects, stemming from lattice atoms thermal motion and accounts for it within the resulting effective nuclear cross-section data. The effects pertain essentially to resonant scattering off of heavy nuclei. The formulation, implemented into a standalone code, produces effective nuclear scattering data that are then supplied directly into the DRAGON lattice physics code where the effects on Doppler Reactivity and neutron flux are demonstrated. The correct accounting for the crystal lattice effects influences the estimated values for the probability of neutron absorption and scattering,more » which in turn affect the estimation of core reactivity and burnup characteristics. The results show an increase in values of Doppler temperature feedback coefficients up to -10% for UOX and MOX LWR fuels compared to the corresponding values derived using the traditional asymptotic elastic scattering kernel. This paper also summarizes the results done on this topic to date.« less

Are the changes in observed functioning after multi-disciplinary rehabilitation of patients with fibromyalgia associated with changes in pain self-efficacy?

PubMed

Rasmussen, Marianne Uggen; Amris, Kirstine; Rydahl-Hansen, Susan; Danneskiold-Samsoe, Bente; Mortensen, Erik Lykke; Christensen, Robin; H Sjölund, Bengt

2017-08-01

To examine the hypothesis that change in pain self-efficacy is associated with observed and self-reported activity, pain intensity, catastrophizing, and quality of life after multi-disciplinary rehabilitation of fibromyalgia patients. In-depth analyses of secondary outcomes of a randomized-controlled trial. Women (N = 187) with fibromyalgia. Outcomes were Pain Self-Efficacy, Assessment of Motor and Process Skills (AMPS), SF-36 Physical Function (SF-36-PF), pain intensity, and SF-36 Mental Composite Score (SF-36-MCS) to assess quality of life and pain catastrophizing. Individual and group associations between outcomes were examined. Individual changes in pain self-efficacy were not associated with changes in observed activity: AMPS motor (r s  = 0.08, p = 0.27) and process (r s  = 0.12, p = 0.11), not even in those patients with a clinically relevant improvement in observed functioning (38.5%), and only weakly or moderatly with changes in SF-36-PF; (r s  = 0.31, p < 0.0001), SF-36-MSC; (r s  = 0.41, p < 0.0001), and pain catastrophizing (r s  = -0.31, p < 0.0001). No differences in pain self-efficacy were observed between the rehabilitated group and controls (difference: 1.61; 95% CI: -0.84 to 4.06; p = 0.24). However, a subgroup (34%) had a clinically relevant improvement in pain self-efficacy. This group was younger (mean age 41.4 vs. 45.8, p = 0.01), more recently diagnosed (1.8 vs. 2.8 years, p = 0.003), but had an unresolved welfare situation (59% vs. 40%, p = 0.02). The main hypothesis was falsified, as there was no association between pain self-efficacy and actual performance of activity. The relation to functioning may be limited to perceived, cognitive-emotional aspects, as indicated by the weak to moderate correlations to the self-reported measures. Implications for Rehabilitation Improvement in observed activity post multi-disciplinary rehabilitation was not associated with change in pain self-efficacy. Patients performed better after rehabilitation, but did not perceive to have improved their capacity. The relationship between pain self-efficacy and functioning may be limited to cognitive-emotional aspects rather than actual activity. Both observational and self-reported measures should be included in evaluating outcomes of rehabilitation for patients with fibromyalgia.

Underground laboratories in Asia

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

Lin, Shin Ted, E-mail: linst@mails.phys.sinica.edu.tw; Yue, Qian, E-mail: yueq@mail.tsinghua.edu.cn

2015-08-17

Deep underground laboratories in Asia have been making huge progress recently because underground sites provide unique opportunities to explore the rare-event phenomena for the study of dark matter searches, neutrino physics and nuclear astrophysics as well as the multi-disciplinary researches based on the low radioactive environments. The status and perspectives of Kamioda underground observatories in Japan, the existing Y2L and the planned CUP in Korea, India-based Neutrino Observatory (INO) in India and China JinPing Underground Laboratory (CJPL) in China will be surveyed.

Underground laboratories in Asia

NASA Astrophysics Data System (ADS)

Lin, Shin Ted; Yue, Qian

2015-08-01

Deep underground laboratories in Asia have been making huge progress recently because underground sites provide unique opportunities to explore the rare-event phenomena for the study of dark matter searches, neutrino physics and nuclear astrophysics as well as the multi-disciplinary researches based on the low radioactive environments. The status and perspectives of Kamioda underground observatories in Japan, the existing Y2L and the planned CUP in Korea, India-based Neutrino Observatory (INO) in India and China JinPing Underground Laboratory (CJPL) in China will be surveyed.

The National Superconducting Cyclotron Laboratory

NASA Astrophysics Data System (ADS)

Gelbke, C. Korad; Morrissey, D. J.; York, R. C.

1996-10-01

The National Superconducting Cyclotron Laboratory (NSCL) at Michigan State University has constructed and operates two superconducting cyclotrons for research in nuclear science, accelerator and instrumental physics. The K500, the world's first superconducting cyclotron, was commissioned in 1982 and the K1200, the world's most powerful cyclotron, was commissioned in 1988. Heavy-ion beams across the entire periodic table produced in a pair of ECR ion sources and accelerated to energies on the order of 100 MeV/A are delivered to a modern and versatile complement of experimental apparatus, including the new S800 high-resolution superconducting magnetic spectrograph now undergoing initial testing. The diverse variety of beams are used for studies of the quantum-statistical properties of hot nuclei, the liquid-gas phase transition in nuclear matter, and for nuclear structure research, particularly with radioactive ion beams from the A1200 fragment separator. The NSCL provides radioactive nuclear beams out to the limits of stability on both the neutron-rich and the proton-rich sides of the valley of stability. The laboratory is also used for multi-disciplinary research in astrophysics, condensed matter physics, geophysics, medicine, and biology. The NSCL has recently proposed a major upgrade of its facility based on coupled operation of the two cyclotrons. The upgrade will provide large increases in beam intensities for radioactive beam production and increased energies of the heaviest beams.

CRTC2 Is a Coactivator of GR and Couples GR and CREB in the Regulation of Hepatic Gluconeogenesis.

PubMed

Hill, Micah J; Suzuki, Shigeru; Segars, James H; Kino, Tomoshige

2016-01-01

Glucocorticoid hormones play essential roles in the regulation of gluconeogenesis in the liver, an adaptive response that is required for the maintenance of circulating glucose levels during fasting. Glucocorticoids do this by cooperating with glucagon, which is secreted from pancreatic islets to activate the cAMP-signaling pathway in hepatocytes. The cAMP-response element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a coactivator known to be specific to CREB and plays a central role in the glucagon-mediated activation of gluconeogenesis in the early phase of fasting. We show here that CRTC2 also functions as a coactivator for the glucocorticoid receptor (GR). CRTC2 strongly enhances GR-induced transcriptional activity of glucocorticoid-responsive genes. CRTC2 physically interacts with the ligand-binding domain of the GR through a region spanning amino acids 561-693. Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB. CRTC2 is required for the maintenance of blood glucose levels during fasting in mice by enhancing the GR transcriptional activity on both the G6p and phosphoenolpyruvate carboxykinase (Pepck) genes. Finally, CRTC2 modulates the transcriptional activity of the progesterone receptor, indicating that it may influence the transcriptional activity of other steroid/nuclear receptors. Taken together, these results reveal that CRTC2 plays an essential role in the regulation of hepatic gluconeogenesis through coordinated regulation of the glucocorticoid/GR- and glucagon/CREB-signaling pathways on the key genes G6P and PEPCK.

Final Report: SciDAC Computational Astrophysics Consortium (at Princeton University)

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

Burrows, Adam

Supernova explosions are the central events in astrophysics. They are the major agencies of change in the interstellar medium, driving star formation and the evolution of galaxies. Their gas remnants are the birthplaces of the cosmic rays. Such is their brightness that they can be used as standard candles to measure the size and geometry of the universe and their investigation draws on particle and nuclear physics, radiative transfer, kinetic theory, gravitational physics, thermodynamics, and the numerical arts. Hence, supernovae are unrivaled astrophysical laboratories. We will develop new state-of-the-art multi-dimensional radiation hydrodynamic codes to address this and other related astrophysicalmore » phenomena.« less

Effects of an Encapsulated Fruit and Vegetable Juice Concentrate on Obesity-Induced Systemic Inflammation: A Randomised Controlled Trial.

PubMed

Williams, Evan J; Baines, Katherine J; Berthon, Bronwyn S; Wood, Lisa G

2017-02-08

Phytochemicals from fruit and vegetables reduce systemic inflammation. This study examined the effects of an encapsulated fruit and vegetable (F&V) juice concentrate on systemic inflammation and other risk factors for chronic disease in overweight and obese adults. A double-blinded, parallel, randomized placebo-controlled trial was conducted in 56 adults aged ≥40 years with a body mass index (BMI) ≥28 kg/m². Before and after eight weeks daily treatment with six capsules of F&V juice concentrate or placebo, peripheral blood gene expression (microarray, quantitative polymerase chain reaction (qPCR)), plasma tumour necrosis factor (TNF)α (enzyme-linked immunosorbent assay (ELISA)), body composition (Dual-energy X-ray absorptiometry (DEXA)) and lipid profiles were assessed. Following consumption of juice concentrate, total cholesterol, low-density lipoprotein (LDL) cholesterol and plasma TNFα decreased and total lean mass increased, while there was no change in the placebo group. In subjects with high systemic inflammation at baseline (serum C-reactive protein (CRP) ≥3.0 mg/mL) who were supplemented with the F&V juice concentrate ( n = 16), these effects were greater, with decreased total cholesterol, LDL cholesterol and plasma TNFα and increased total lean mass; plasma CRP was unchanged by the F&V juice concentrate following both analyses. The expression of several genes involved in lipogenesis, the nuclear factor-κB (NF-κB) and 5' adenosine monophosphate-activated protein kinase (AMPK) signalling pathways was altered, including phosphomevalonate kinase (PMVK), zinc finger AN1-type containing 5 (ZFAND5) and calcium binding protein 39 (CAB39), respectively. Therefore, F&V juice concentrate improves the metabolic profile, by reducing systemic inflammation and blood lipid profiles and, thus, may be useful in reducing the risk of obesity-induced chronic disease.

Velocity Model Using the Large-N Seismic Array from the Source Physics Experiment (SPE)

NASA Astrophysics Data System (ADS)

Chen, T.; Snelson, C. M.

2016-12-01

The Source Physics Experiment (SPE) is a multi-institutional, multi-disciplinary project that consists of a series of chemical explosions conducted at the Nevada National Security Site (NNSS). The goal of SPE is to understand the complicated effect of geological structures on seismic wave propagation and source energy partitioning, develop and validate physics-based modeling, and ultimately better monitor low-yield nuclear explosions. A Large-N seismic array was deployed at the SPE site to image the full 3D wavefield from the most recent SPE-5 explosion on April 26, 2016. The Large-N seismic array consists of 996 geophones (half three-component and half vertical-component sensors), and operated for one month, recording the SPE-5 shot, ambient noise, and additional controlled-sources (a large hammer). This study uses Large-N array recordings of the SPE-5 chemical explosion to develop high resolution images of local geologic structures. We analyze different phases of recorded seismic data and construct a velocity model based on arrival times. The results of this study will be incorporated into the large modeling and simulation efforts as ground-truth further validating the models.

Large-N Seismic Deployment at the Source Physics Experiment (SPE) Site

NASA Astrophysics Data System (ADS)

Chen, T.; Snelson, C. M.; Mellors, R. J.; Pitarka, A.

2015-12-01

The Source Physics Experiment (SPE) is multi-institutional and multi-disciplinary project that consists of a series of chemical explosion experiments at the Nevada National Security Site. The goal of SPE is to understand the complicated effect of earth structures on source energy partitioning and seismic wave propagation, develop and validate physics-based monitoring, and ultimately better discriminate low-yield nuclear explosions from background seismicity. Deployment of a large number of seismic sensors is planned for SPE to image the full 3-D wavefield with about 500 three-component sensors and 500 vertical component sensors. This large-N seismic deployment will operate near the site of SPE-5 shot for about one month, recording the SPE-5 shot, ambient noise, and additional controlled-sources. This presentation focuses on the design of the large-N seismic deployment. We show how we optimized the sensor layout based on the geological structure and experiment goals with a limited number of sensors. In addition, we will also show some preliminary record sections from deployment. This work was conducted under Contract No. DE-AC52-06NA25946 with the U.S. Department of Energy.

Antimicrobial Peptides and Nanotechnology, Recent Advances and Challenges.

PubMed

Biswaro, Lubhandwa S; da Costa Sousa, Mauricio G; Rezende, Taia M B; Dias, Simoni C; Franco, Octavio L

2018-01-01

Antimicrobial peptides are sequences of amino acids, which present activity against microorganisms. These peptides were discovered over 70 years ago, and are abundant in nature from soil bacteria, insects, amphibians to mammals and plants. They vary in amino acids number, the distance between amino acids within individual peptide structure, net charge, solubility and other physical chemical properties as well as differ in mechanism of action. These peptides may provide an alternative treatment to conventional antibiotics, which encounter resistance such as the peptide nisin applied in treating methicillin resistant Staphylococcus aureus (MRSA) or may behave synergistically with known antibiotics against parasites for instance, nisin Z when used in synergy with ampicillin reported better activity against Pseudomonas fluorescens than when the antibiotic was alone. AMPs are known to be active against viruses, bacteria, fungi and protozoans. Nanotechnology is an arena which explores the synthesis, characterization and application of an array of delivery systems at a one billionth of meter scale. Such systems are implemented to deliver drugs, proteins, vaccines, and peptides. The role of nanotechnology in delivering AMPs is still at its early development stage. There are challenges of incorporating AMPs into drug delivery system. This review intends to explore in depth, the role of nanotechnology in delivering AMPs as well as presenting the current advances and accompanying challenges of the technology.

Multi-step Monte Carlo calculations applied to nuclear reactor instrumentation - source definition and renormalization to physical values

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

Radulovic, Vladimir; Barbot, Loic; Fourmentel, Damien

Significant efforts have been made over the last few years in the French Alternative Energies and Atomic Energy Commission (CEA) to adopt multi-step Monte Carlo calculation schemes in the investigation and interpretation of the response of nuclear reactor instrumentation detectors (e.g. miniature ionization chambers - MICs and self-powered neutron or gamma detectors - SPNDs and SPGDs). The first step consists of the calculation of the primary data, i.e. evaluation of the neutron and gamma flux levels and spectra in the environment where the detector is located, using a computational model of the complete nuclear reactor core and its surroundings. Thesemore » data are subsequently used to define sources for the following calculation steps, in which only a model of the detector under investigation is used. This approach enables calculations with satisfactory statistical uncertainties (of the order of a few %) within regions which are very small in size (the typical volume of which is of the order of 1 mm{sup 3}). The main drawback of a calculation scheme as described above is that perturbation effects on the radiation conditions caused by the detectors themselves are not taken into account. Depending on the detector, the nuclear reactor and the irradiation position, the perturbation in the neutron flux as primary data may reach 10 to 20%. A further issue is whether the model used in the second step calculations yields physically representative results. This is generally not the case, as significant deviations may arise, depending on the source definition. In particular, as presented in the paper, the injudicious use of special options aimed at increasing the computation efficiency (e.g. reflective boundary conditions) may introduce unphysical bias in the calculated flux levels and distortions in the spectral shapes. This paper presents examples of the issues described above related to a case study on the interpretation of the signal from different types of SPNDs, which were recently irradiated in the Jozef Stefan Institute TRIGA Mark II reactor in Ljubljana, Slovenia, and provides recommendations on how they can be overcome. The paper concludes with a discussion on the renormalization of the results from the second step calculations, to obtain accurate physical values. (authors)« less

Crystal structure of the protein At3g01520, a eukaryotic universal stress protein-like protein from Arabidopsis thaliana in complex with AMP.

PubMed

Kim, Do Jin; Bitto, Eduard; Bingman, Craig A; Kim, Hyun-Jung; Han, Byung Woo; Phillips, George N

2015-07-01

Members of the universal stress protein (USP) family are conserved in a phylogenetically diverse range of prokaryotes, fungi, protists, and plants and confer abilities to respond to a wide range of environmental stresses. Arabidopsis thaliana contains 44 USP domain-containing proteins, and USP domain is found either in a small protein with unknown physiological function or in an N-terminal portion of a multi-domain protein, usually a protein kinase. Here, we report the first crystal structure of a eukaryotic USP-like protein encoded from the gene At3g01520. The crystal structure of the protein At3g01520 was determined by the single-wavelength anomalous dispersion method and refined to an R factor of 21.8% (Rfree = 26.1%) at 2.5 Å resolution. The crystal structure includes three At3g01520 protein dimers with one AMP molecule bound to each protomer, comprising a Rossmann-like α/β overall fold. The bound AMP and conservation of residues in the ATP-binding loop suggest that the protein At3g01520 also belongs to the ATP-binding USP subfamily members. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Interaction of AIP with protein kinase A (cAMP-dependent protein kinase).

PubMed

Schernthaner-Reiter, Marie Helene; Trivellin, Giampaolo; Stratakis, Constantine A

2018-05-02

Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene cause mostly somatotropinomas and/or prolactinomas in a subset of familial isolated pituitary adenomas (FIPA). AIP has been shown to interact with phosphodiesterases (PDEs) and G proteins, suggesting a link to the cyclic AMP (cAMP)-dependent protein kinase (PKA) pathway. Upregulation of PKA is seen in sporadic somatotropinomas that carry GNAS1 mutations, and those in Carney complex that are due to PRKAR1A mutations. To elucidate the mechanism of AIP-dependent pituitary tumorigenesis, we studied potential functional and physical interactions of AIP with PKA's main subunits PRKAR1A (R1α) and PRKACA (Cα). We found that AIP physically interacts with both R1α and Cα; this interaction is enhanced when all three components are present, but maintained during Cα-R1α dissociation by PKA pathway activation, indicating that AIP binds Cα/R1α both in complex and separately. The interaction between AIP and R1α/Cα is reduced when the frequent AIP pathogenic mutation p.R304* is present. AIP protein levels are regulated both by translation and the ubiquitin/proteasome pathway and Cα stabilizes both AIP and R1α protein levels. AIP reduction by siRNA leads to an increase of PKA pathway activity, which is disproportionately enhanced during PDE4-inhibition. We show that AIP interacts with the PKA pathway on multiple levels, including a physical interaction with both the main regulatory (R1α) and catalytic (Cα) PKA subunits and a functional interaction with PDE4-dependent PKA activation. These findings provide novel insights on the mechanisms of AIP-dependent pituitary tumorigenesis.

Improving Prompt Temperature Feedback by Stimulating Doppler Broadening in Heterogeneous Composite Nuclear Fuel Forms

NASA Astrophysics Data System (ADS)

Morrison, Christopher

Nuclear fuels with similar aggregate material composition, but with different millimeter and micrometer spatial configurations of the component materials can have very different safety and performance characteristics. This research focuses on modeling and attempting to engineer heterogeneous combinations of nuclear fuels to improve negative prompt temperature feedback in response to reactivity insertion accidents. Improvements in negative prompt temperature feedback are proposed by developing a tailored thermal resistance in the nuclear fuel. In the event of a large reactivity insertion, the thermal resistance allows for a faster negative Doppler feedback by temporarily trapping heat in material zones with strong absorption resonances. A multi-physics simulation framework was created that could model large reactivity insertions. The framework was then used to model a comparison of a heterogeneous fuel with a tailored thermal resistance and a homogeneous fuel without the tailored thermal resistance. The results from the analysis confirmed the fundamental premise of prompt temperature feedback and provide insights into the neutron spectrum dynamics throughout the transient process. A trade study was conducted on infinite lattice fuels to help map a design space to study and improve prompt temperature feedback with many results. A multi-scale fuel pin analysis was also completed to study more realistic geometries. The results of this research could someday allow for novel nuclear fuels that would behave differently than current fuels. The idea of having a thermal barrier coating in the fuel is contrary to most current thinking. Inherent resistance to reactivity insertion accidents could enable certain reactor types once considered vulnerable to reactivity insertion accidents to be reevaluated in light of improved negative prompt temperature feedback.

In Vivo Cardiovascular Pharmacology of 2′,3′-cAMP, 2′-AMP, and 3′-AMP in the Rat

PubMed Central

Mi, Zaichuan

2013-01-01

The naturally occurring purine 2′,3′-cAMP is metabolized in vitro to 2′-AMP and 3′-AMP, which are subsequently metabolized to adenosine. Whether in vivo 2′,3′-cAMP, 2′-AMP, or 3′-AMP are rapidly converted to adenosine and exert rapid effects via adenosine receptors is unknown. To address this question, we compared the cardiovascular and renal effects of 2′,3′-cAMP, 2′-AMP, 3′-AMP, 3′,5′-cAMP, 5′-AMP, and adenosine in vivo in the rat. Purines were infused intravenously while monitoring mean arterial blood pressure (MABP), heart rate (HR), cardiac output, and renal and mesenteric blood flows. Total peripheral (TPR), renal vascular (RVR), and mesenteric vascular (MVR) resistances were calculated. Urine was collected for determination of urine excretion rate [urine volume (UV)]. When sufficient urine was available, the sodium excretion rate (Na+ER) and glomerular filtration rate (GFR) were determined. 2′,3′-cAMP, 2′-AMP, and 3′-AMP dose-dependently and profoundly reduced MABP, HR, TPR, and MVR with efficacy and potency similar to adenosine and 5′-AMP. These effects of 2′,3′-cAMP, 2′-AMP, and 3′-AMP were attenuated by blockade of adenosine receptors with 1,3-dipropyl-8-(p-sulfophenyl)xanthine. 2′,3′-cAMP, 2′-AMP, 3′-AMP, adenosine, and 5′-AMP variably affected RVR, but profoundly (nearly 100%) decreased UV at higher doses. GFR and Na+ER could be measured at the lower doses and were suppressed by 2′,3′-cAMP, 2′-AMP, and 3′-AMP, but not by adenosine or 5′-AMP. 2′,3′-cAMP increased urinary excretion rates of 2′-AMP, 3′-AMP, and adenosine. 3′,5′-cAMP exerted no adverse hemodynamic effects yet increased urinary adenosine as efficiently as 2′,3′-cAMP. Conclusions: In vivo 2′,3′-cAMP is rapidly converted to adenosine. Because both cAMPs increase adenosine in the urinary compartment, these agents may provide unique therapeutic opportunities. PMID:23759508

2′,3′-cAMP, 3′-AMP, and 2′-AMP inhibit human aortic and coronary vascular smooth muscle cell proliferation via A2B receptors

PubMed Central

Ren, Jin; Gillespie, Delbert G.

2011-01-01

Rat vascular smooth muscle cells (VSMCs) from renal microvessels metabolize 2′,3′-cAMP to 2′-AMP and 3′-AMP, and these AMPs are converted to adenosine that inhibits microvascular VSMC proliferation via A2B receptors. The goal of this study was to test whether this mechanism also exists in VSMCs from conduit arteries and whether it is similarly expressed in human vs. rat VSMCs. Incubation of rat and human aortic VSMCs with 2′,3′-cAMP concentration-dependently increased levels of 2′-AMP and 3′-AMP in the medium, with a similar absolute increase in 2′-AMP vs. 3′-AMP. In contrast, in human coronary VSMCs, 2′,3′-cAMP increased 2′-AMP levels yet had little effect on 3′-AMP levels. In all cell types, 2′,3′-cAMP increased levels of adenosine, but not 5′-AMP, and 2′,3′-AMP inhibited cell proliferation. Antagonism of A2B receptors (MRS-1754), but not A1 (1,3-dipropyl-8-cyclopentylxanthine), A2A (SCH-58261), or A3 (VUF-5574) receptors, attenuated the antiproliferative effects of 2′,3′-cAMP. In all cell types, 2′-AMP, 3′-AMP, and 5′-AMP increased adenosine levels, and inhibition of ecto-5′-nucleotidase blocked this effect of 5′-AMP but not that of 2′-AMP nor 3′-AMP. Also, 2′-AMP, 3′-AMP, and 5′-AMP, like 2′,3′-cAMP, exerted antiproliferative effects that were abolished by antagonism of A2B receptors with MRS-1754. In conclusion, VSMCs from conduit arteries metabolize 2′,3′-cAMP to AMPs, which are metabolized to adenosine. In rat and human aortic VSMCs, both 2′-AMP and 3′-AMP are involved in this process, whereas, in human coronary VSMCs, 2′,3′-cAMP is mainly converted to 2′-AMP. Because adenosine inhibits VSMC proliferation via A2B receptors, local vascular production of 2′,3′-cAMP may protect conduit arteries from atherosclerosis. PMID:21622827

AMPS sciences objectives and philosophy. [Atmospheric, Magnetospheric and Plasmas-in-Space project on Spacelab

NASA Technical Reports Server (NTRS)

Schmerling, E. R.

1975-01-01

The Space Shuttle will open a new era in the exploration of earth's near-space environment, where the weight and power capabilities of Spacelab and the ability to use man in real time add important new features. The Atmospheric, Magnetospheric, and Plasmas-in-Space project (AMPS) is conceived of as a facility where flexible core instruments can be flown repeatedly to perform different observations and experiments. The twin thrusts of remote sensing of the atmosphere below 120 km and active experiments on the space plasma are the major themes. They have broader implications in increasing our understanding of plasma physics and of energy conversion processes elsewhere in the universe.

Scoping Study of Machine Learning Techniques for Visualization and Analysis of Multi-source Data in Nuclear Safeguards

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

Cui, Yonggang

In implementation of nuclear safeguards, many different techniques are being used to monitor operation of nuclear facilities and safeguard nuclear materials, ranging from radiation detectors, flow monitors, video surveillance, satellite imagers, digital seals to open source search and reports of onsite inspections/verifications. Each technique measures one or more unique properties related to nuclear materials or operation processes. Because these data sets have no or loose correlations, it could be beneficial to analyze the data sets together to improve the effectiveness and efficiency of safeguards processes. Advanced visualization techniques and machine-learning based multi-modality analysis could be effective tools in such integratedmore » analysis. In this project, we will conduct a survey of existing visualization and analysis techniques for multi-source data and assess their potential values in nuclear safeguards.« less

Extracellular 2′,3′-cAMP-adenosine pathway in proximal tubular, thick ascending limb, and collecting duct epithelial cells

PubMed Central

Gillespie, Delbert G.

2013-01-01

In a previous study, we demonstrated that human proximal tubular epithelial cells obtained from a commercial source metabolized extracellular 2′,3′-cAMP to 2′-AMP and 3′-AMP and extracellular 2′-AMP and 3′-AMP to adenosine (the extracellular 2′,3′-cAMP-adenosine pathway; extracellular 2′,3′-cAMP → 2′-AMP + 3′-AMP → adenosine). The purpose of this study was to investigate the metabolism of extracellular 2′,3′-cAMP in proximal tubular vs. thick ascending limb vs. collecting duct epithelial cells freshly isolated from their corresponding nephron segments obtained from rat kidneys. In epithelial cells from all three nephron segments, 1) extracellular 2′,3′-cAMP was metabolized to 2′-AMP and 3′-AMP, with 2′-AMP > 3′-AMP, 2) the metabolism of extracellular 2′,3′-cAMP to 2′-AMP and 3′-AMP was not inhibited by either 3-isobutyl-1-methylxanthine (phosphodiesterase inhibitor) or 1,3-dipropyl-8-p-sulfophenylxanthine (ecto-phosphodiesterase inhibitor), 3) extracellular 2′,3′-cAMP increased extracellular adenosine levels, 4) 3′-AMP and 2′-AMP were metabolized to adenosine with an efficiency similar to that of 5′-AMP, and 5) the metabolism of 5′-AMP, 3′-AMP, and 2′-AMP was not inhibited by α,β-methylene-adenosine-5′-diphosphate (CD73 inhibitor). These results support the conclusion that renal epithelial cells all along the nephron can metabolize extracellular 2′,3′-cAMP to 2′-AMP and 3′-AMP and can efficiently metabolize extracellular 2′-AMP and 3′-AMP to adenosine and that the metabolic enzymes involved are not the classical phosphodiesterases nor ecto-5′-nucleotidase (CD73). Because 2′,3′-cAMP is released by injury and because previous studies demonstrate that the extracellular 2′,3′-cAMP-adenosine pathway stimulates epithelial cell proliferation via adenosine A2B receptors, the present results suggest that the extracellular 2′,3′-cAMP-adenosine pathway may help restore epithelial cells along the nephron following kidney injury. PMID:23077101

The Brain In Vivo Expresses the 2′,3′-cAMP-Adenosine Pathway

PubMed Central

Verrier, Jonathan D.; Jackson, Travis C.; Bansal, Rashmi; Kochanek, Patrick M.; Puccio, Ava M.; Okonkwo, David O.; Jackson, Edwin K.

2012-01-01

Although multiple biochemical pathways produce adenosine, studies suggest that the 2′,3′-cAMP-adenosine pathway (2′,3′-cAMP → 2′-AMP/3′-AMP → adenosine) contributes to adenosine production in some cells/tissues/organs. To determine whether the 2′,3′-cAMP-adenosine pathway exists in vivo in the brain, we delivered to the brain (gray matter and white matter separately) via the inflow perfusate of a microdialysis probe either 2′,3′-cAMP, 3′,5′-cAMP, 2′-AMP, 3′-AMP, or 5′-AMP and measured the recovered metabolites in the microdialysis outflow perfusate with mass spectrometry. In both gray and white matter, 2′,3′-cAMP increased 2′-AMP, 3′-AMP and adenosine, and 3′,5′-cAMP increased 5′-AMP and adenosine. In both brain regions, 2′-AMP, 3-AMP and 5′-AMP were converted to adenosine. Microdialysis experiments in 2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNPase) wild-type mice demonstrated that traumatic brain injury (TBI; controlled cortical impact model) activated the brain 2,3′-cAMP-adenosine pathway; similar experiments in CNPase knockout mice indicated that CNPase was involved in the metabolism of endogenous 2′,3′-cAMP to 2′-AMP and to adenosine. In CSF from TBI patients, 2′,3′-cAMP was significantly increased in the initial 12 hours after injury and strongly correlated with CSF levels of 2′-AMP, 3′-AMP, adenosine and inosine. We conclude that in vivo, 2′,3′-cAMP is converted to 2′-AMP/3′-AMP, and these AMPs are metabolized to adenosine. This pathway exists endogenously in both mice and humans. PMID:22360621

An Inorganic Microsphere Composite for the Selective Removal of Cesium 137 from Acidic Nuclear Waste Solutions - Parts 1 and 2

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

T. J. Tranter; T. A. Vereschchagina; V. Utgikar

2009-03-01

A new inorganic ion exchange composite for removing radioactive cesium from acidic waste streams has been developed. The new material consists of ammonium molybdophosphate, (NH4)3P(Mo3O10)4•3H2O (AMP), synthesized within hollow aluminosilicate microspheres (AMP-C), which are produced as a by-product from coal combustion. The selective cesium exchange capacity of this inorganic composite was evaluated in bench-scale column tests using simulated sodium bearing waste solution as a surrogate for the acidic tank waste currently stored at the Idaho National Laboratory (INL). Total cesium loading on the columns at saturation agreed very well with equilibrium values predicted from isotherm experiments performed previously. A numericalmore » algorithm for solving the governing partial differential equations (PDE) for cesium uptake was developed using the intraparticle mass transfer coefficient obtained from previous batch kinetic experiments. Solutions to the governing equations were generated to obtain the cesium concentration at the column effluent as a function of throughput volume using the same conditions as those used for the actual column experiments. The numerical solutions of the PDE fit the column break through data quite well for all the experimental conditions in the study. The model should therefore provide a reliable prediction of column performance at larger scales. A new inorganic ion exchange composite consisting of ammonium molybdophosphate, (NH4)3P(Mo3O10)4•3H2O (AMP), synthesized within hollow aluminosilicate microspheres (AMP-C) has been developed. Two different batches of the sorbent were produced resulting in 20% and 25% AMP loading for two and three loading cycles, respectively. The selective cesium exchange capacity of this inorganic composite was evaluated using simulated sodium bearing waste solution as a surrogate for the acidic tank waste currently stored at the Idaho National Laboratory (INL). Equilibrium isotherms obtained from these experiments were very favorable for cesium uptake and indicated maximum cesium loading of approximately 9 % by weight of dry AMP. Batch kinetic experiments were also performed to obtain the necessary data to estimate the effective diffusion coefficient for cesium in the sorbent particle. These experiments resulted in effective intraparticle cesium diffusivity coefficients of 4.99 x 10-8 cm2/min and 4.72 x 10-8 cm2/min for the 20% and 25 % AMP-C material, respectively.« less

Pit-1/growth hormone factor 1 splice variant expression in the rhesus monkey pituitary gland and the rhesus and human placenta.

PubMed

Schanke, J T; Conwell, C M; Durning, M; Fisher, J M; Golos, T G

1997-03-01

We have examined the expression of Pit-1 messenger RNA (mRNA) splice variants in the nonhuman primate pituitary and in rhesus and human placenta. Full-length complementary DNAs (cDNAs) representing Pit-1 and the Pit-1 beta splice variants were cloned from a rhesus monkey pituitary cDNA library and were readily detectable by RT-PCR with rhesus pituitary gland RNA. The Pit-1T variant previously reported in mouse pituitary tumor cell lines was not detectable in normal rhesus pituitary tissue, although two novel splice variants were detected. A cDNA approximating the rat Pit-1 delta 4 variant was cloned but coded for a truncated and presumably nonfunctional protein. Only by using a nested RT-PCR approach were Pit-1 and Pit-1 beta variants consistently detectable in both human and rhesus placental tissue. The Pit-1 beta variant mRNA was not detectable in JEG-3 choriocarcinoma cells unless the cells were stimulated with 8-Br-cAMP. Immunoblot studies with nuclear extracts from primary rhesus syncytiotrophoblast cultures or JEG-3 choriocarcinoma cells indicated that although mRNA levels were very low, Pit-1 protein was detectable in differentiated cytotrophoblasts, and levels increased after treatment with 8-Br-cAMP. Two major species of Pit-1 protein were detected that corresponded to the two major bands in rat pituitary GH3 cell nuclear extracts. Low levels of slightly larger bands also were seen, which may represent Pit-1 beta protein or phosphorylated species. We conclude that Pit-1 splice variants expressed in the primate pituitary gland differ from those in the rodent gland and that the Pit-1 and Pit-1 beta mRNAs expressed in the placenta give rise to a pattern of protein expression similar to that seen in pituitary cells, which is inducible by treatment with 8-Br-cAMP.

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

Park, Sun Young; Kim, Ji-Hee; Lee, Sang Joon

Surfactin, one of the most powerful biosurfactants, is a bacterial cyclic lipopeptide. Here, we investigated the anti-neuroinflammatory properties of surfactin in lipoteichoic acid (LTA)-stimulated BV-2 microglial cells. Surfactin significantly inhibited excessive production of the pro-inflammatory mediators TNF-α, IL-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), prostaglandin E{sub 2} (PGE{sub 2}), nitric oxide (NO) and reactive oxygen species (ROS), and suppressed the expression of matrix metalloproteinase-9 (MMP-9), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequent mechanistic studies revealed that surfactin inhibited LTA-induced nuclear factor-kappaB (NF-κB) and signal transducer and activator of transcription-1 (STAT-1) activation. However, surfactin increases the phosphorylation of the STAT-3, amore » component of the homeostatic mechanism causing anti-inflammatory events. We also demonstrated that surfactin induces heme oxygenase-1 (HO-1) expression and nuclear factor-regulated factor-2 (Nrf-2) activation, and that the anti-inflammatory effects of surfactin are abrogated by small interfering RNA-mediated knock-down of HO-1 or Nrf-2. Interestingly, we found that surfactin increased the level of cAMP and induced phosphorylation of cAMP responsive element binding protein (CREB) in microglial cells. Furthermore, treatment with the protein kinase A (PKA) inhibitor, H-89, blocked HO-1 induction by surfactin and abolished surfactin's suppressive effects on ROS and NO production. These results indicate that HO-1 and its upstream effector, PKA, play a pivotal role in the anti-neuroinflammatory response of surfactin in LTA-stimulated microglia. Therefore, surfactin might have therapeutic potential for neuroprotective agents to treat inflammatory and neurodegenerative diseases. - Highlights: ► Surfactin inhibits proinflammatory mediator synthesis in LTA-activated BV-2 cells. ► Surfactin suppresses NF-κB and STAT-1, but potentiates phosphorylation of STAT-3. ► Surfactin induces HO-1 expression and Nrf-2 activation. ► Surfactin induces cAMP and CREB phosphorylation. ► PKA inhibitor blocks HO-1 induction and surfactin’s antiinflammatory effects.« less

Towards a Conceptual Diagnostic Survey in Nuclear Physics

ERIC Educational Resources Information Center

Kohnle, Antje; Mclean, Stewart; Aliotta, Marialuisa

2011-01-01

Understanding students' prior beliefs in nuclear physics is a first step towards improving nuclear physics instruction. This paper describes the development of a diagnostic survey in nuclear physics covering the areas of radioactive decay, binding energy, properties of the nuclear force and nuclear reactions, that was administered to students at…

Evaluation of copper-64-labeled somatostatin agonists and antagonist in sstr2-transfected cell lines that are positive and negative for p53: implications for cancer therapy

PubMed Central

Nguyen, Kim; Parry, Jesse J.; Rogers, Buck E.; Anderson, Carolyn J.

2011-01-01

Objectives Radiolabeled somatostatin analogs have become important agents for molecular imaging and targeted radiotherapy of somatostatin receptor-positive tumors. Here we determine the effect of the tumor suppressor protein, p53, on trafficking 64Cu to tumor cell nuclei from DOTA vs.CB-TE2A-conjugated agonist Y3-TATE and the antagonist 64Cu-CB-TE2A-sst2-ANT in cell lines that are positive or negative for p53. Methods Receptor binding, internalization, cAMP and nuclear localization studies were performed with the SSTr2 agonists, 64Cu-CB-TE2A-Y3-TATE and 64Cu-DOTA-Y3-TATE vs. antagonist, 64Cu-CB-TE2A-sst2-ANT, in SSTr2-transfected p53 +/+ and −/− HCT116 colorectal carcinoma cells. Results The antagonist, 64Cu-CB-TE2A-sst2-ANT, bound 8-9-fold more SSTr2 binding sites than did the 64Cu-labeled agonists. 64Cu-CB-TE2A-Y3-TATE was more efficiently internalized than 64Cu-DOTA-Y3-TATE, while 64Cu-CB-TE2A-sst2-ANT showed lower, yet significant levels of internalization. CB-TE2A-Y3-TATE acted as a full agonist, inhibiting cAMP production, whereas CB-TE2A-sst2-ANT showed no inhibition of cAMP production.The 64Cu from agonists 64Cu-DOTA-Y3-TATE and 64Cu-CB-TE2A-Y3-TATE showed greater nuclear localization at 24 h in p53 +/+ vs. −/− cells; however, there was no difference in the levels of 64Cu from the antagonist based on p53 status. Surprisingly, the DOTA and CB-TE2A-conjugated agonists showed similar nuclear localization in the p53 +/+ and −/− cells, suggesting no difference in 64Cu release from these chelators in the HCT116 cell lines. Conclusion Based on thesein vitro data, the agonist 64Cu-CB-TE2A-Y3-TATE demonstrated the most promise as an agent for targeted radiotherapy in p53 positive, SSTr2-positive tumors. PMID:22056254

Nuclear and Particle Physics, Astrophysics and Cosmology : T-2 : LANL

Science.gov Websites

linked in Search T-2, Nuclear and Particle Physics, Astrophysics and Cosmology T-2 Home T Division Focus Areas Nuclear Information Service Nuclear Physics Particle Physics Astrophysics Cosmology CONTACTS Group energy security, heavy ion physics, nuclear astrophysics, physics beyond the standard model, neutrino

Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

NASA Astrophysics Data System (ADS)

Rose, P. B.; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I.

2016-04-01

Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.

A simple procedure for γ- γ lifetime measurements using multi-element fast-timing arrays

NASA Astrophysics Data System (ADS)

Régis, J.-M.; Dannhoff, M.; Jolie, J.

2018-07-01

The lifetimes of nuclear excited states are important observables in nuclear physics. Their precise measurement is of key importance for developing and testing nuclear models as they are directly linked with the quantum nature of the nuclear system. The γ- γ timing technique represents a direct lifetime determination by means of time-difference measurements between the γ rays which directly feed and decay from a nuclear excited state. Using arrays of very-fast scintillator detectors, picosecond-sensitive time-difference measurements can be performed. We propose to construct a symmetric energy-energy-time cube as is usually done to perform γ- γ coincidence analyses and lifetime determination with high-resolution germanium detectors. By construction, a symmetric mean time-walk characteristics is obtained, that can be precisely determined and used as a single time correction for all the data independently of the detectors. We present the results of timing characteristics measurements of an array with six LaBr3(Ce) detectors, as obtained using a 152Eu point γ-ray source. Compared with a single detector pair, the time resolution of the symmetrised time-difference spectra of the array is nearly unaffected.

Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

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

Rose, Jr., P. B.; Erickson, A. S.; Mayer, Michael F.

Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method frommore » being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.« less

Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

DOE PAGES

Rose, P. B.; Erickson, A. S.; Mayer, M.; ...

2016-04-18

Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method frommore » being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.« less

Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

PubMed Central

Rose, P. B.; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I.

2016-01-01

Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications. PMID:27087555

Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging.

PubMed

Rose, P B; Erickson, A S; Mayer, M; Nattress, J; Jovanovic, I

2016-04-18

Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as "searching for a needle in a haystack" because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material's areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.

On the use of X-ray absorption spectroscopy to elucidate the structure of lutetium adenosine mono- and triphosphate complexes.

PubMed

Mostapha, S; Berthon, C; Fontaine-Vive, F; Gaysinski, M; Guérin, L; Guillaumont, D; Massi, L; Monfardini, I; Solari, P L; Thomas, O P; Charbonnel, M C; Den Auwer, C

2014-02-01

Although the physiological impact of the actinide elements as nuclear toxicants has been widely investigated for half a century, a description of their interactions with biological molecules remains limited. It is however of primary importance to better assess the determinants of actinide speciation in cells and more generally in living organisms to unravel the molecular processes underlying actinide transport and deposition in tissues. The biological pathways of this family of elements in case of accidental contamination or chronic natural exposure (in the case of uranium rich soils for instance) are therefore a crucial issue of public health and of societal impact. Because of the high chemical affinity of those actinide elements for phosphate groups and the ubiquity of such chemical functions in biochemistry, phosphate derivatives are considered as probable targets of these cations. Among them, nucleotides and in particular adenosine mono- (AMP) and triphosphate (ATP) nucleotides occur in more chemical reactions than any other compounds on the earth's surface, except water, and are therefore critical target molecules. In the present study, we are interested in trans-plutonium actinide elements, in particular americium and curium that are more rarely considered in environmental and bioaccumulation studies than early actinides like uranium, neptunium and plutonium. A first step in this strategy is to work with chemical analogues like lanthanides that are not radioactive and therefore allow extended physical chemical characterization to be conducted that are difficult to perform with radioactive materials. We describe herein the interaction of lutetium(III) with adenosine AMP and ATP. With AMP and ATP, insoluble amorphous compounds have been obtained with molar ratios of 1:2 and 1:1, respectively. With an excess of ATP, with 1:2 molar ratio, a soluble complex has been obtained. A combination of spectroscopic techniques (IR, NMR, ESI-MS, EXAFS) together with quantum chemical calculations has been implemented in order to assess the lutetium coordination arrangement for the two nucleotides. In all the complexes described in the article, the lutetium cation is coordinated by the phosphate groups of the nucleotide plus additional putative water molecules with various tridimensional arrangements. With AMP 1:2 and ATP 1:1 solid-state compounds, polynuclear complexes are assumed to be obtained. In contrast, with ATP 1:2 soluble compound, the Lu coordination sphere is saturated by two ATP ligands, and this favors the formation of a mononuclear complex. In order to further interpret the EXAFS data obtained at the Lu LIII edge, model structures have been calculated for the 1:1 and 1:2 ATP complexes. They are discussed and compared to the EXAFS best fit metrical parameters.

Applications of nuclear physics

NASA Astrophysics Data System (ADS)

Hayes, A. C.

2017-02-01

Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applications of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.

Applications of nuclear physics

DOE PAGES

Hayes-Sterbenz, Anna Catherine

2017-01-10

Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applicationsmore » of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Lastly, each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.« less

Applications of nuclear physics.

PubMed

Hayes, A C

2017-02-01

Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applications of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.

Applications of nuclear physics

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

Hayes-Sterbenz, Anna Catherine

Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applicationsmore » of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Lastly, each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.« less

Cell-wall recycling and synthesis in Escherichia coli and Pseudomonas aeruginosa - their role in the development of resistance.

PubMed

Dhar, Supurna; Kumari, Hansi; Balasubramanian, Deepak; Mathee, Kalai

2018-01-01

The bacterial cell-wall that forms a protective layer over the inner membrane is called the murein sacculus - a tightly cross-linked peptidoglycan mesh unique to bacteria. Cell-wall synthesis and recycling are critical cellular processes essential for cell growth, elongation and division. Both de novo synthesis and recycling involve an array of enzymes across all cellular compartments, namely the outer membrane, periplasm, inner membrane and cytoplasm. Due to the exclusivity of peptidoglycan in the bacterial cell-wall, these players are the target of choice for many antibacterial agents. Our current understanding of cell-wall biochemistry and biogenesis in Gram-negative organisms stems mostly from studies of Escherichia coli. An incomplete knowledge on these processes exists for the opportunistic Gram-negative pathogen, Pseudomonas aeruginosa. In this review, cell-wall synthesis and recycling in the various cellular compartments are compared and contrasted between E. coli and P. aeruginosa. Despite the fact that there is a remarkable similarity of these processes between the two bacterial species, crucial differences alter their resistance to β-lactams, fluoroquinolones and aminoglycosides. One of the common mediators underlying resistance is the amp system whose mechanism of action is closely associated with the cell-wall recycling pathway. The activation of amp genes results in expression of AmpC β-lactamase through its cognate regulator AmpR which further regulates multi-drug resistance. In addition, other cell-wall recycling enzymes also contribute to antibiotic resistance. This comprehensive summary of the information should spawn new ideas on how to effectively target cell-wall processes to combat the growing resistance to existing antibiotics.

From cutting-edge pointwise cross-section to groupwise reaction rate: A primer

NASA Astrophysics Data System (ADS)

Sublet, Jean-Christophe; Fleming, Michael; Gilbert, Mark R.

2017-09-01

The nuclear research and development community has a history of using both integral and differential experiments to support accurate lattice-reactor, nuclear reactor criticality and shielding simulations, as well as verification and validation efforts of cross sections and emitted particle spectra. An important aspect to this type of analysis is the proper consideration of the contribution of the neutron spectrum in its entirety, with correct propagation of uncertainties and standard deviations derived from Monte Carlo simulations, to the local and total uncertainty in the simulated reactions rates (RRs), which usually only apply to one application at a time. This paper identifies deficiencies in the traditional treatment, and discusses correct handling of the RR uncertainty quantification and propagation, including details of the cross section components in the RR uncertainty estimates, which are verified for relevant applications. The methodology that rigorously captures the spectral shift and cross section contributions to the uncertainty in the RR are discussed with quantified examples that demonstrate the importance of the proper treatment of the spectrum profile and cross section contributions to the uncertainty in the RR and subsequent response functions. The recently developed inventory code FISPACT-II, when connected to the processed nuclear data libraries TENDL-2015, ENDF/B-VII.1, JENDL-4.0u or JEFF-3.2, forms an enhanced multi-physics platform providing a wide variety of advanced simulation methods for modelling activation, transmutation, burnup protocols and simulating radiation damage sources terms. The system has extended cutting-edge nuclear data forms, uncertainty quantification and propagation methods, which have been the subject of recent integral and differential, fission, fusion and accelerators validation efforts. The simulation system is used to accurately and predictively probe, understand and underpin a modern and sustainable understanding of the nuclear physics that is so important for many areas of science and technology; advanced fission and fuel systems, magnetic and inertial confinement fusion, high energy, accelerator physics, medical application, isotope production, earth exploration, astrophysics and homeland security.

Genome-wide analysis of signal transducers and regulators of mitochondrial dysfunction in Saccharomyces cerevisiae.

PubMed

Singh, Keshav K; Rasmussen, Anne Karin; Rasmussen, Lene Juel

2004-04-01

Mitochondrial dysfunction is a hallmark of cancer cells. However, genetic response to mitochondrial dysfunction during carcinogenesis is unknown. To elucidate genetic response to mitochondrial dysfunction we used Saccharomyces cerevisiae as a model system. We analyzed genome-wide expression of nuclear genes involved in signal transduction and transcriptional regulation in a wild-type yeast and a yeast strain lacking the mitochondrial genome (rho(0)). Our analysis revealed that the gene encoding cAMP-dependent protein kinase subunit 3 (PKA3) was upregulated. However, the gene encoding cAMP-dependent protein kinase subunit 2 (PKA2) and the VTC1, PTK2, TFS1, CMK1, and CMK2 genes, involved in signal transduction, were downregulated. Among the known transcriptional factors, OPI1, MIG2, INO2, and ROX1 belonged to the upregulated genes, whereas MSN4, MBR1, ZMS1, ZAP1, TFC3, GAT1, ADR1, CAT8, and YAP4 including RFA1 were downregulated. RFA1 regulates DNA repair genes at the transcriptional level. RFA is also involved directly in DNA recombination, DNA replication, and DNA base excision repair. Downregulation of RFA1 in rho(0) cells is consistent with our finding that mitochondrial dysfunction leads to instability of the nuclear genome. Together, our data suggest that gene(s) involved in mitochondria-to-nucleus communication play a role in mutagenesis and may be implicated in carcinogenesis.

Motivation toward Physical Exercise and Subjective Wellbeing: The Mediating Role of Trait Self-Control

PubMed Central

Briki, Walid

2016-01-01

Motivation toward physical exercise (MPE) and trait self-control (TSC) were identified as key predictors of subjective wellbeing (SWB). However, there has not been any research designed to examine the mediating role of TSC in the relationship between MPE and SWB. The present study utilizes self-determination theory, control-process theory of self-regulation, and theory of multiple pathways of TSC in order to examine whether TSC mediates the relationships of autonomous MPE (A-MPE), controlled MPE (C-MPE), and impersonal MPE (NO-MPE) with SWB using structural equation modeling (XLSTAT PLS). Three hundred seventeen adult American individuals (Mage = 32.97, SDage = 11.30), who reported to be regular exercisers, voluntarily answered questionnaires assessing MPE, TSC, and SWB. Correlational analyses revealed positive relationships between A-MPE, TSC, and SWB, and negative relationships of C-MPE and NO-MPE with TSC and SWB. Mediation analyses revealed that TSC mediated the relationships of A-MPE (partial mediation) and C-MPE (full mediation) with SWB, but did not mediate the relationship between NO-MPE and SWB. The estimates of the quality of the hypothesized model were acceptable (outer model GoF = 0.935; absolute GoF = 0.330; relative GoF = 0.942; inner model GoF = 1.008; R2 = 36.947%). Finally, this study supports the view that MPE can influence SWB through TSC, and incites to pursue the examination of the relationships between self-determined motivation, self-regulation mechanisms, and health-related outcomes. PMID:27761126

A concise review on advances in development of small molecule anti-inflammatory therapeutics emphasising AMPK: An emerging target.

PubMed

Gejjalagere Honnappa, Chethan; Mazhuvancherry Kesavan, Unnikrishnan

2016-12-01

Inflammatory diseases are complex, multi-factorial outcomes of evolutionarily conserved tissue repair processes. For decades, non-steroidal anti-inflammatory drugs and cyclooxygenase inhibitors, the primary drugs of choice for the management of inflammatory diseases, addressed individual targets in the arachidonic acid pathway. Unsatisfactory safety and efficacy profiles of the above have necessitated the development of multi-target agents to treat complex inflammatory diseases. Current anti-inflammatory therapies still fall short of clinical needs and the clinical trial results of multi-target therapeutics are anticipated. Additionally, new drug targets are emerging with improved understanding of molecular mechanisms controlling the pathophysiology of inflammation. This review presents an outline of small molecules and drug targets in anti-inflammatory therapeutics with a summary of a newly identified target AMP-activated protein kinase, which constitutes a novel therapeutic pathway in inflammatory pathology. © The Author(s) 2016.

Inhibitory effects of albuterol and fenoterol on RANTES and IP-10 expression in bronchial epithelial cells.

PubMed

Lam, Ka-Pan; Chu, Yu-Te; Lee, Min-Sheng; Chen, Huan-Nan; Wang, Wei-Li; Tok, Teck-Siang; Chin, Yow-Yue; Chen, Solomon Chih-Cheng; Kuo, Chang-Hung; Hung, Chih-Hsing

2011-06-01

Short-acting β2-adrenoreceptor agonist (SABA) is the major asthma reliever as indicated in the GINA guidelines. Regulated on activation, normal T expressed and secreted (RANTES) is a chemokine that attracts eosinophils, mast cells, and basophils toward site of allergic inflammation. Interferon γ-inducible protein (IP)-10 is a Th1-related chemokine that is also important in asthmatic inflammation and also involved in our immune defense against pathogens. Bronchial epithelial cells are first-line barrier against invasive pathogen and also have immunomodulatory function. However, whether albuterol and fenoterol (two SABAs) have modulatory effects on RANTES and IP-10 expression in bronchial epithelial cells is unknown. The human bronchial epithelial cell lines, BEAS-2B cells, were pre-treated with different concentrations of albuterol, fenoterol or dibutyryl-cAMP (a cyclic AMP analog) before polyinosinic-polycytidylic acid (poly I:C) stimulation. In some condition, BEAS-2B cells were pre-treated with ICI-118551, a selective β2-adrenoreceptor antagonist, 30 min before albuterol or fenoterol treatment. The levels of RANTES and IP-10 were measured by ELISA. Intracellular signaling was investigated using cAMP assay, mitogen-activated protein kinase (MAPK) inhibitor, nuclear factor (NF)-κB inhibitor, and western blot. Albuterol and fenoterol suppressed poly I:C-induced RANTES and IP-10 expression of BEAS-2B cells. ICI-118551 could partly reverse the suppressive effects of albuterol and fenoterol on RANTES and IP-10 expression. Albuterol and fenoterol increased intracellular cAMP levels. Dibutyryl-cAMP conferred the similar effects of albuterol and fenoterol. Western blot revealed that albuterol suppressed p-ERK, p-JNK and pp38, and also their associated kinase expression. Albuterol had no effect on pp65 expression. Albuterol and fenoterol could suppress poly I:C-induced RANTES and IP-10 expression in human bronchial epithelial cells via at least partly the β2-adrenoreceptor-cAMP and the MAPK pathways, implicating that albuterol and fenoterol could exert anti-inflammatory effect and benefit asthmatic patients by suppressing RANTES and IP-10 expression. However, these suppressive effects of albuterol and fenoterol may inhibit the defense against viral infection. © 2010 John Wiley & Sons A/S.

Pharmacological AMP-kinase activators have compartment-specific effects on cell physiology.

PubMed

Kodiha, Mohamed; Ho-Wo-Cheong, Dennis; Stochaj, Ursula

2011-12-01

5'-AMP-activated kinase (AMPK) regulates numerous biological events and is an essential target for the treatment of type 2 diabetes. The objectives of the present study were first to determine the compartment-specific effects of three established AMPK activators on Thr172 phosphorylation of the α-subunit, an indicator of AMPK activation. Second, we examined how cytoplasmic and nuclear processes are modulated by pharmacological AMPK activators. Specifically, the impact of phenformin, resveratrol, and 5-aminoimidazole-4-carboxamide riboside (AICAR) on Thr172 phosphorylation in the cytoplasm and nucleus was quantified by different methods. To analyze how these activators change cell physiology, we measured the inactivation of acetyl-CoA-carboxylase 1, a predominantly cytoplasmic enzyme that is crucial for lipid metabolism. As a criterion for activities associated with the nucleus, de novo RNA synthesis in nucleoli was quantified. Our studies demonstrate that pharmacological activators of AMPK can alter the balance between nuclear and cytoplasmic AMPK pools. Thus, phenformin and resveratrol caused a strong activation of AMPK in the cytoplasm, whereas the effect was less pronounced in nuclei. By contrast, AICAR elicited a comparable rise in Thr172 phosphorylation in both compartments. Notably, these activators differed drastically in their effects on physiological processes that are located in distinct subcellular compartments. All compounds led to a substantial inactivation of acetyl-CoA-carboxylase 1 in the cytoplasm, with only minor changes to the nuclear enzyme. In the nucleolus, transcription was strongly inhibited by resveratrol, while a moderate inhibition was observed with phenformin and AICAR. Taken together, the compartment-specific phosphorylation of AMPK and downstream events are determined by the activator.

Applications of Nuclear and Particle Physics Technology: Particles & Detection — A Brief Overview

NASA Astrophysics Data System (ADS)

Weisenberger, Andrew G.

A brief overview of the technology applications with significant societal benefit that have their origins in nuclear and particle physics research is presented. It is shown through representative examples that applications of nuclear physics can be classified into two basic areas: 1) applying the results of experimental nuclear physics and 2) applying the tools of experimental nuclear physics. Examples of the application of the tools of experimental nuclear and particle physics research are provided in the fields of accelerator and detector based technologies namely synchrotron light sources, nuclear medicine, ion implantation and radiation therapy.

SiC/SiC Cladding Materials Properties Handbook

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

Snead, Mary A.; Katoh, Yutai; Koyanagi, Takaaki

When a new class of material is considered for a nuclear core structure, the in-pile performance is usually assessed based on multi-physics modeling in coordination with experiments. This report aims to provide data for the mechanical and physical properties and environmental resistance of silicon carbide (SiC) fiber–reinforced SiC matrix (SiC/SiC) composites for use in modeling for their application as accidenttolerant fuel cladding for light water reactors (LWRs). The properties are specific for tube geometry, although many properties can be predicted from planar specimen data. This report presents various properties, including mechanical properties, thermal properties, chemical stability under normal and offnormalmore » operation conditions, hermeticity, and irradiation resistance. Table S.1 summarizes those properties mainly for nuclear-grade SiC/SiC composites fabricated via chemical vapor infiltration (CVI). While most of the important properties are available, this work found that data for the in-pile hydrothermal corrosion resistance of SiC materials and for thermal properties of tube materials are lacking for evaluation of SiC-based cladding for LWR applications.« less

Conference on Real-Time Computer Applications in Nuclear, Particle and Plasma Physics, 6th, Williamsburg, VA, May 15-19, 1989, Proceedings

NASA Technical Reports Server (NTRS)

Pordes, Ruth (Editor)

1989-01-01

Papers on real-time computer applications in nuclear, particle, and plasma physics are presented, covering topics such as expert systems tactics in testing FASTBUS segment interconnect modules, trigger control in a high energy physcis experiment, the FASTBUS read-out system for the Aleph time projection chamber, a multiprocessor data acquisition systems, DAQ software architecture for Aleph, a VME multiprocessor system for plasma control at the JT-60 upgrade, and a multiasking, multisinked, multiprocessor data acquisition front end. Other topics include real-time data reduction using a microVAX processor, a transputer based coprocessor for VEDAS, simulation of a macropipelined multi-CPU event processor for use in FASTBUS, a distributed VME control system for the LISA superconducting Linac, a distributed system for laboratory process automation, and a distributed system for laboratory process automation. Additional topics include a structure macro assembler for the event handler, a data acquisition and control system for Thomson scattering on ATF, remote procedure execution software for distributed systems, and a PC-based graphic display real-time particle beam uniformity.

Binding of Losartan to Angiotensin AT1 Receptors Increases Dopamine D1 Receptor Activation

PubMed Central

Li, Dong; Scott, Lena; Crambert, Susanne; Zelenin, Sergey; Eklöf, Ann-Christine; Di Ciano, Luis; Ibarra, Fernando

2012-01-01

Signaling through both angiotensin AT1 receptors (AT1R) and dopamine D1 receptors (D1R) modulates renal sodium excretion and arterial BP. AT1R and D1R form heterodimers, but whether treatment with AT1R antagonists functionally modifies D1R via allosterism is unknown. In this study, the AT1R antagonist losartan strengthened the interaction between AT1R and D1R and increased expression of D1R on the plasma membrane in vitro. In rat proximal tubule cells that express endogenous AT1R and D1R, losartan increased cAMP generation. Losartan increased cAMP in HEK 293a cells transfected with both AT1R and D1R, but it did not increase cAMP in cells transfected with either receptor alone, suggesting that losartan induces D1R activation. Furthermore, losartan did not increase cAMP in HEK 293a cells expressing AT1R and mutant S397/S398A D1R, which disrupts the physical interaction between AT1R and D1R. In vivo, administration of a D1R antagonist significantly attenuated the antihypertensive effect of losartan in rats with renal hypertension. Taken together, these data imply that losartan might exert its antihypertensive effect both by inhibiting AT1R signaling and by enhancing D1R signaling. PMID:22193384

Endurance Factors Improve Hippocampal Neurogenesis and Spatial Memory in Mice

ERIC Educational Resources Information Center

Kobilo, Tali; Yuan, Chunyan; van Praag, Henriette

2011-01-01

Physical activity improves learning and hippocampal neurogenesis. It is unknown whether compounds that increase endurance in muscle also enhance cognition. We investigated the effects of endurance factors, peroxisome proliferator-activated receptor [delta] agonist GW501516 and AICAR, activator of AMP-activated protein kinase on memory and…

Comparison of experimental results of a Quad-CZT array detector, a NaI(Tl), a LaBr3(Ce), and a HPGe for safeguards applications

NASA Astrophysics Data System (ADS)

Kwak, S.-W.; Choi, J.; Park, S. S.; Ahn, S. H.; Park, J. S.; Chung, H.

2017-11-01

A compound semiconductor detector, CdTe (or CdZnTe), has been used in various areas including nuclear safeguards applications. To address its critical drawback, low detection efficiency, which leads to a long measurement time, a Quad-CZT array-based gamma-ray spectrometer in our previous study has been developed by combining four individual CZT detectors. We have re-designed the developed Quad-CZT array system to make it more simple and compact for a hand-held gamma-ray detector. The objective of this paper aims to compare the improved Quad-CZT array system with the traditional gamma-ray spectrometers (NaI(Tl), LaBr3(Ce), HPGe); these detectors currently have been the most commonly used for verification of nuclear materials. Nuclear materials in different physical forms in a nuclear facility of Korea were measured by the Quad-CZT array system and the existing gamma-ray detectors. For measurements of UO2 pellets and powders, and fresh fuel rods, the Quad-CZT array system turned out to be superior to the NaI(Tl) and LaBr3(Ce). For measurements of UF6 cylinders with a thick wall, the Quad-CZT array system and HPGe gave similar accuracy under the same measurement time. From the results of the field tests conducted, we can conclude that the improved Quad-CZT array system would be used as an alternative to HPGes and scintillation detectors for the purpose of increasing effectivenss and efficiency of safeguards applications. This is the first paper employing a multi-element CZT array detector for measurement of nuclear materials—particularly uranium in a UF6 cylinder—in a real nuclear facility. The present work also suggests that the multi-CZT array system described in this study would be one promising method to address a serious weakness of CZT-based radiation detection.

Recent Progress in the Development of a Multi-Layer Green's Function Code for Ion Beam Transport

NASA Technical Reports Server (NTRS)

Tweed, John; Walker, Steven A.; Wilson, John W.; Tripathi, Ram K.

2008-01-01

To meet the challenge of future deep space programs, an accurate and efficient engineering code for analyzing the shielding requirements against high-energy galactic heavy radiation is needed. To address this need, a new Green's function code capable of simulating high charge and energy ions with either laboratory or space boundary conditions is currently under development. The computational model consists of combinations of physical perturbation expansions based on the scales of atomic interaction, multiple scattering, and nuclear reactive processes with use of the Neumann-asymptotic expansions with non-perturbative corrections. The code contains energy loss due to straggling, nuclear attenuation, nuclear fragmentation with energy dispersion and downshifts. Previous reports show that the new code accurately models the transport of ion beams through a single slab of material. Current research efforts are focused on enabling the code to handle multiple layers of material and the present paper reports on progress made towards that end.

Modeling of complex wear behavior associated with grid-to-rod fretting in light water nuclear reactors

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

Blau, P. J.; Qu, J.; Lu, R.

One significant concern in the operation of light water nuclear reactors is the fretting wear damage to fuel cladding from flow-induced vibrations. For years, research on the grid-to-rod fretting (GTRF) phenomena has been underway in countries where nuclear power production is a significant industry. Under the auspices of the U.S. Department of Energy Consortium for Advanced Simulation of Light Water Reactors, an effort has been underway to develop and test an engineering wear model for zirconium alloy fuel rod cladding against a supporting grid. Furthermore, the multi-stage model accounts for oxide layers and wear rate transitions. Our paper describes themore » basis for a GTRF engineering wear model, the physical significance of the wear factor it contains, and recent progress toward model validation based on a fretting wear testing apparatus that accounts for coolant temperature, pressure, and the presence of periodic impacts (gaps) in grid/rod contact.« less

Highlights lecture EANM 2016: "Embracing molecular imaging and multi-modal imaging: a smart move for nuclear medicine towards personalized medicine".

PubMed

Aboagye, Eric O; Kraeber-Bodéré, Françoise

2017-08-01

The 2016 EANM Congress took place in Barcelona, Spain, from 15 to 19 October under the leadership of Prof. Wim Oyen, chair of the EANM Scientific Committee. With more than 6,000 participants, this congress was the most important European event in nuclear medicine, bringing together a multidisciplinary community involved in the different fields of nuclear medicine. There were over 600 oral and 1,200 poster or e-Poster presentations with an overwhelming focus on development and application of imaging for personalized care, which is timely for the community. Beyond FDG PET, major highlights included progress in the use of PSMA and SSTR receptor-targeted radiopharmaceuticals and associated theranostics in oncology. Innovations in radiopharmaceuticals for imaging pathologies of the brain and cardiovascular system, as well as infection and inflammation, were also highlighted. In the areas of physics and instrumentation, multimodality imaging and radiomics were highlighted as promising areas of research.

Modeling of complex wear behavior associated with grid-to-rod fretting in light water nuclear reactors

DOE PAGES

Blau, P. J.; Qu, J.; Lu, R.

2016-09-21

One significant concern in the operation of light water nuclear reactors is the fretting wear damage to fuel cladding from flow-induced vibrations. For years, research on the grid-to-rod fretting (GTRF) phenomena has been underway in countries where nuclear power production is a significant industry. Under the auspices of the U.S. Department of Energy Consortium for Advanced Simulation of Light Water Reactors, an effort has been underway to develop and test an engineering wear model for zirconium alloy fuel rod cladding against a supporting grid. Furthermore, the multi-stage model accounts for oxide layers and wear rate transitions. Our paper describes themore » basis for a GTRF engineering wear model, the physical significance of the wear factor it contains, and recent progress toward model validation based on a fretting wear testing apparatus that accounts for coolant temperature, pressure, and the presence of periodic impacts (gaps) in grid/rod contact.« less

New Insight into Nuclear Reactions in Solids

NASA Astrophysics Data System (ADS)

Miley, George H.

2003-04-01

Earlier work by the author disclosed evidence for nuclear transmutations in multi-layer thin-film Ni/Pd electrodes loaded to a high ratio of hydrogen/film metal using an electrolytic technique [1]. Non-natural isotopes abundances were found for select products. A distinctive characteristic of this and similar experiments by others is a product yield curve vs. mass with four high yield peaks distributed between low and high masses. Attempts to explain this observation have evolved around the original swimming electron layer (SEL) theory [2]. In addition, CR-39 track detector measurements have revealed low-level emission of 1.6 MeV protons and 16 MeV alpha particles from the front face of the thin film electrodes during runs [3]. Most recently Mitsubishi Corp. researchers have reported a real-time transmutation measurement using built-in XPS diagnostics where a surface layer of Sr-88 was transmuted into Mo-96 over a 200 hour run period during the diffusion of deuterium through a multi-layer thin-film Pd/CaO substrate [4]. Likewise in a companion experiment, Cs-133 was transmuted into Pr-141. These products exhibit a large deviation from natural isotopic abundance, and the characteristic signature is a mass change of 8 and charge change of 4. These various phenomena along with a preliminary theory involving SEL and orbital mixing will be presented. The objective is to provide a unified understanding of both types of experiments presented in Refs. 1 and 3. [1] G.H. Miley and J. A. Patterson, "Nuclear Transmutations in Thin-Film Nickel Coatings Undergoing Electrolysis," J. New Energy, 1, 3, 5-30 (1996). [2] H. Hora, et al., "Screening in Cold Fusion Derived from D D Reactions," Physics Ltrs. A, 175, 138-143, (1993). [3] A. Lipson, et al., "In-situ long - range alpha particles and X-ray detection in Pd thin film-cathodes during electrolysis in, Li2SO4/H2O, Bult. APS, 47, 1,Pt. II, 1219, Indianapolis, (2002). [4] Y. Iwamura, T. Itoh, et al., "Low energy nuclear reaction induced by D gas permeation through multilayer film," Japanese J. Physics, 41, pt. 1, 7A, 4642, (2002).

Multi-physics CFD simulations in engineering

NASA Astrophysics Data System (ADS)

Yamamoto, Makoto

2013-08-01

Nowadays Computational Fluid Dynamics (CFD) software is adopted as a design and analysis tool in a great number of engineering fields. We can say that single-physics CFD has been sufficiently matured in the practical point of view. The main target of existing CFD software is single-phase flows such as water and air. However, many multi-physics problems exist in engineering. Most of them consist of flow and other physics, and the interactions between different physics are very important. Obviously, multi-physics phenomena are critical in developing machines and processes. A multi-physics phenomenon seems to be very complex, and it is so difficult to be predicted by adding other physics to flow phenomenon. Therefore, multi-physics CFD techniques are still under research and development. This would be caused from the facts that processing speed of current computers is not fast enough for conducting a multi-physics simulation, and furthermore physical models except for flow physics have not been suitably established. Therefore, in near future, we have to develop various physical models and efficient CFD techniques, in order to success multi-physics simulations in engineering. In the present paper, I will describe the present states of multi-physics CFD simulations, and then show some numerical results such as ice accretion and electro-chemical machining process of a three-dimensional compressor blade which were obtained in my laboratory. Multi-physics CFD simulations would be a key technology in near future.

GPR-4 Is a Predicted G-Protein-Coupled Receptor Required for Carbon Source-Dependent Asexual Growth and Development in Neurospora crassa

PubMed Central

Li, Liande; Borkovich, Katherine A.

2006-01-01

The filamentous fungus Neurospora crassa is able to utilize a wide variety of carbon sources. Here, we examine the involvement of a predicted G-protein-coupled receptor (GPCR), GPR-4, during growth and development in the presence of different carbon sources in N. crassa. Δgpr-4 mutants have reduced mass accumulation compared to the wild type when cultured on high levels of glycerol, mannitol, or arabinose. The defect is most severe on glycerol and is cell density dependent. The genetic and physical relationship between GPR-4 and the three N. crassa Gα subunits (GNA-1, GNA-2, and GNA-3) was explored. All three Gα mutants are defective in mass accumulation when cultured on glycerol. However, the phenotypes of Δgna-1 and Δgpr-4 Δgna-1 mutants are identical, introduction of a constitutively activated gna-1 allele suppresses the defects of the Δgpr-4 mutation, and the carboxy terminus of GPR-4 interacts most strongly with GNA-1 in the yeast two-hybrid assay. Although steady-state cyclic AMP (cAMP) levels are normal in Δgpr-4 strains, exogenous cAMP partially remediates the dry mass defects of Δgpr-4 mutants on glycerol medium and Δgpr-4 strains lack the transient increase in cAMP levels observed in the wild type after addition of glucose to glycerol-grown liquid cultures. Our results support the hypothesis that GPR-4 is coupled to GNA-1 in a cAMP signaling pathway that regulates the response to carbon source in N. crassa. GPR-4-related GPCRs are present in the genomes of several filamentous ascomycete fungal pathogens, raising the possibility that a similar pathway regulates carbon sensing in these organisms. PMID:16896213

Development of a Stellar Model-Fitting Pipeline for Asteroseismic Data from the TESS Mission

NASA Astrophysics Data System (ADS)

Metcalfe, Travis

The launch of NASA's Kepler space telescope in 2009 revolutionized the quality and quantity of observational data available for asteroseismic analysis. Prior to the Kepler mission, solar-like oscillations were extremely difficult to observe, and data only existed for a handful of the brightest stars in the sky. With the necessity of studying one star at a time, the traditional approach to extracting the physical properties of the star from the observations was an uncomfortably subjective process. A variety of experts could use similar tools but come up with significantly different answers. Not only did this subjectivity have the potential to undermine the credibility of the technique, it also hindered the compilation of a uniform sample that could be used to draw broader physical conclusions from the ensemble of results. During a previous award from NASA, we addressed these issues by developing an automated and objective stellar model-fitting pipeline for Kepler data, and making it available through the Asteroseismic Modeling Portal (AMP). This community modeling tool has allowed us to derive reliable asteroseismic radii, masses and ages for large samples of stars (Metcalfe et al. 2014), but the most recent observations are so precise that we are now limited by systematic uncertainties associated with our stellar models. With a huge archive of Kepler data available for model validation, and the next planet-hunting satellite already approved for an expected launch in 2017, now is the time to incorporate what we have learned into the next generation of AMP. We propose to improve the reliability of our estimates of stellar properties over the next 4 years by collaborating with two open-source development projects that will augment and ultimately replace the stellar evolution and pulsation models that we now use in AMP. Our current treatment of the oscillations does not include the effects of radiative or convective heat-exchange, nor does it account for the influence of turbulent pressure on the equilibrium structure of the star. The GYRE pulsation code (Townsend & Teitler 2013) already includes a treatment of radiative heat-exchange, and its flexibility will allow us to incorporate additional contributions as they are quantified. We will also take advantage of the numerical stability and modular architecture of the MESA stellar evolution code (Paxton et al. 2013) to evaluate additional sources of bias that arise from the adopted input physics, and to incorporate heavy element diffusion and settling, which is not stable for all types of stars with our current models. GYRE was designed to interface with MESA models, and MESA includes modules to run our current models for easy comparison. Both projects have active developer communities, and are designed to run in parallel on multi-core architectures. The existing sample of targets with Kepler observations spanning more than 3 years will provide a rich data set to validate our new models and methods. The golden age of asteroseismology for main sequence and subgiant stars owes a great debt to the Kepler mission, but it promises to continue with the expected 2017 launch of NASA's Transiting Exoplanet Survey Satellite (TESS). While Kepler was able to provide asteroseismic data for hundreds of targets and could simultaneously monitor 512 stars with 1-minute sampling, TESS will observe the brightest Sun-like stars in the sky at a cadence sufficient to detect solar-like oscillations in thousands of targets. These bright stars are much better characterized than Kepler targets, with known distances and reliable constraints from ground-based observations, making asteroseismic analysis even more accurate. With several years of development time available, AMP promises to be ready to convert the avalanche of data from TESS into reliable estimates of the properties of the solar system's nearest neighbors.

Alteration of Cyclic-AMP Response Element Binding Protein in the Postmortem Brain of Subjects with Bipolar Disorder and Schizophrenia

PubMed Central

Ren, Xinguo; Rizavi, Hooriyah S.; Khan, Mansoor A.; Bhaumik, Runa; Dwivedi, Yogesh; Pandey, Ghanshyam N.

2013-01-01

Background Abnormalities of cyclic-AMP (cAMP) response element binding protein (CREB) function has been suggested in bipolar (BP) illness and schizophrenia (SZ), based on both indirect and direct evidence. To further elucidate the role of CREB in these disorders, we studied CREB expression and function in two brain areas implicated in these disorders, i.e., dorsolateral prefrontal cortex (DLPFC) and cingulate gyrus (CG). Methods We determined CREB protein expression using Western blot technique, CRE-DNA binding using gel shift assay, and mRNA expression using real-time RT-polymerase chain reaction (qPCR) in DLPFC and CG of the postmortem brain of BP (n = 19), SZ (n = 20), and normal control (NC, n = 20) subjects. Results We observed that CREB protein and mRNA expression and CRE-DNA binding activity were significantly decreased in the nuclear fraction of DLPFC and CG obtained from BP subjects compared with NC subjects. However, the protein and mRNA expression and CRE-DNA binding in SZ subjects was significantly decreased in CG, but not in DLPFC, compared with NC. Conclusion These studies thus indicate region-specific abnormalities of CREB expression and function in both BP and SZ. They suggest that abnormalities of CREB in CG may be associated with both BP and SZ, but its abnormality in DLPFC is specific to BP illness. PMID:24148789

Adsorption of arsenic ions on Brazilian sepiolite: effect of contact time, pH, concentration, and calorimetric investigation.

PubMed

Guerra, Denis L; Batista, Adriano C; da Costa, Paulo C Corrêa; Viana, Rúbia R; Airoldi, Claudio

2010-06-01

The original sepiolite clay mineral has been collected from Amazon region, Brazil. The compound 2-aminomethylpyridine (AMP) was anchored onto Amazon sepiolite surface by heterogeneous route. The natural (SPT) and modified (SPT(AMP)) sepiolite samples were characterized by elemental analysis, SEM, N(2) adsorption, and nuclear magnetic nuclei of (29)Si and (13)C. The well-defined peaks obtained in the (13)C NMR spectrum in the 0-160 ppm region confirmed the attachment of organic functional groups as pendant chains bonded into the porous clay. The ability of these materials to remove As(V) from aqueous solution was followed by a series of adsorption isotherms at room temperature and pH 4.0. The maximum number of moles adsorbed was determined to be 7.26×10(-2) and 11.70×10(-2) mmol g(-1) for SPT and SPT(AMP), respectively. In order to evaluate the clay samples as adsorbents in dynamic system, a glass column was fulfilled with clay samples (1.0 g) and it was fed with 2.0×10(-2) mmol dm(-3) As(V) at pH 4.0. The energetic effects caused by metal cations adsorption were determined through calorimetric titrations. Thermodynamics indicated the existence of favorable conditions for such As(V)-nitrogen interactions. Copyright © 2010. Published by Elsevier Inc.

Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes.

PubMed

Goldberg, Alexander A; Richard, Vincent R; Kyryakov, Pavlo; Bourque, Simon D; Beach, Adam; Burstein, Michelle T; Glebov, Anastasia; Koupaki, Olivia; Boukh-Viner, Tatiana; Gregg, Christopher; Juneau, Mylène; English, Ann M; Thomas, David Y; Titorenko, Vladimir I

2010-07-01

In chronologically aging yeast, longevity can be extended by administering a caloric restriction (CR) diet or some small molecules. These life-extending interventions target the adaptable target of rapamycin (TOR) and cAMP/protein kinase A (cAMP/PKA) signaling pathways that are under the stringent control of calorie availability. We designed a chemical genetic screen for small molecules that increase the chronological life span of yeast under CR by targeting lipid metabolism and modulating housekeeping longevity pathways that regulate longevity irrespective of the number of available calories. Our screen identifies lithocholic acid (LCA) as one of such molecules. We reveal two mechanisms underlying the life-extending effect of LCA in chronologically aging yeast. One mechanism operates in a calorie availability-independent fashion and involves the LCA-governed modulation of housekeeping longevity assurance pathways that do not overlap with the adaptable TOR and cAMP/PKA pathways. The other mechanism extends yeast longevity under non-CR conditions and consists in LCA-driven unmasking of the previously unknown anti-aging potential of PKA. We provide evidence that LCA modulates housekeeping longevity assurance pathways by suppressing lipid-induced necrosis, attenuating mitochondrial fragmentation, altering oxidation-reduction processes in mitochondria, enhancing resistance to oxidative and thermal stresses, suppressing mitochondria-controlled apoptosis, and enhancing stability of nuclear and mitochondrial DNA.

The Orphan G Protein-coupled Receptor Gpr175 (Tpra40) Enhances Hedgehog Signaling by Modulating cAMP Levels.

PubMed

Singh, Jaskirat; Wen, Xiaohui; Scales, Suzie J

2015-12-04

The Hedgehog (Hh) signaling pathway plays an essential role in vertebrate embryonic tissue patterning of many developing organs. Signaling occurs predominantly in primary cilia and is initiated by the entry of the G protein-coupled receptor (GPCR)-like protein Smoothened into cilia and culminates in gene transcription via the Gli family of transcription factors upon their nuclear entry. Here we identify an orphan GPCR, Gpr175 (also known as Tpra1 or Tpra40: transmembrane protein, adipocyte associated 1 or of 40 kDa), which also localizes to primary cilia upon Hh stimulation and positively regulates Hh signaling. Interaction experiments place Gpr175 at the level of PKA and upstream of the Gαi component of heterotrimeric G proteins, which itself localizes to cilia and can modulate Hh signaling. Gpr175 or Gαi1 depletion leads to increases in cellular cAMP levels and in Gli3 processing into its repressor form. Thus we propose that Gpr175 coupled to Gαi1 normally functions to inhibit the production of cAMP by adenylyl cyclase upon Hh stimulation, thus maximizing signaling by turning off PKA activity and hence Gli3 repressor formation. Taken together our data suggest that Gpr175 is a novel positive regulator of the Hh signaling pathway. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Multi-junction Thin-film Solar Cells on Flexible Substrates for Space Power

NASA Technical Reports Server (NTRS)

Hepp, Aloysius F.; Smith, Mark; Scofield, John H.; Dickman, John E.; Lush, Gregory B.; Morel, Donald L.; Ferekides, Christos; Dhere, Neelkanth G.

2002-01-01

The ultimate objective of the thin-film program at NASA GRC is development of a 20 percent AM0 thin-film device technology with high power/weight ratio. Several approaches are outlined to improve overall device efficiency and power/weight ratio. One approach involves the use of very lightweight flexible substrates such as polyimides (i.e., Kapton(Trademark)) or metal foil. Also, a compound semiconductor tandem device structure that can meet this objective is proposed and simulated using Analysis of Microelectronic and Photonic Structures (AMPS). AMPS modeling of current devices in tandem format indicate that AM0 efficiencies near 20 percent can be achieved. And with improvements in materials, efficiencies approaching 25 percent are achievable. Several important technical issues need to be resolved to realize these complex devices: development of a wide bandgap material with good electronic properties, development of transparent contacts, and targeting a 2-terminal device structure (with more complicated processing and tunnel junction) or 4-terminal device. Recent progress in the NASA GRC program is outlined.

Preliminary Results for the OECD/NEA Time Dependent Benchmark using Rattlesnake, Rattlesnake-IQS and TDKENO

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

DeHart, Mark D.; Mausolff, Zander; Weems, Zach

2016-08-01

One goal of the MAMMOTH M&S project is to validate the analysis capabilities within MAMMOTH. Historical data has shown limited value for validation of full three-dimensional (3D) multi-physics methods. Initial analysis considered the TREAT startup minimum critical core and one of the startup transient tests. At present, validation is focusing on measurements taken during the M8CAL test calibration series. These exercises will valuable in preliminary assessment of the ability of MAMMOTH to perform coupled multi-physics calculations; calculations performed to date are being used to validate the neutron transport solver Rattlesnake\\cite{Rattlesnake} and the fuels performance code BISON. Other validation projects outsidemore » of TREAT are available for single-physics benchmarking. Because the transient solution capability of Rattlesnake is one of the key attributes that makes it unique for TREAT transient simulations, validation of the transient solution of Rattlesnake using other time dependent kinetics benchmarks has considerable value. The Nuclear Energy Agency (NEA) of the Organization for Economic Cooperation and Development (OECD) has recently developed a computational benchmark for transient simulations. This benchmark considered both two-dimensional (2D) and 3D configurations for a total number of 26 different transients. All are negative reactivity insertions, typically returning to the critical state after some time.« less

Evolving landscape of low-energy nuclear physics publications

DOE PAGES

Pritychenko, B.

2016-10-01

Evolution of low-energy nuclear physics publications over the last 120 years has been analyzed using nuclear physics databases. An extensive study of Nuclear Science References, Experimental Nuclear Reaction Data (EXFOR), and Evaluated Nuclear Structure Data File (ENSDF) contents provides a unique picture of refereed and non-refereed nuclear physics references. Significant fractional contributions of non-refereed reports, private communications and conference proceedings in EXFOR and ENSDF databases in the 1970’s reflect extensive experimental campaigns and an insufficient number of research journals. This trend has been reversed in recent years because the number of measurements is much lower, while number of journals ismore » higher. In addition, nuclear physics results are mainly published in a limited number of journals, such as Physical Review C and Nuclear Physics A. In the present work, historic publication trends and averages have been extracted and analyzed using nuclear data mining techniques. Lastly, the results of this study and implications are discussed and conclusions presented.« less

Evolving landscape of low-energy nuclear physics publications

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

Pritychenko, B.

Evolution of low-energy nuclear physics publications over the last 120 years has been analyzed using nuclear physics databases. An extensive study of Nuclear Science References, Experimental Nuclear Reaction Data (EXFOR), and Evaluated Nuclear Structure Data File (ENSDF) contents provides a unique picture of refereed and non-refereed nuclear physics references. Significant fractional contributions of non-refereed reports, private communications and conference proceedings in EXFOR and ENSDF databases in the 1970’s reflect extensive experimental campaigns and an insufficient number of research journals. This trend has been reversed in recent years because the number of measurements is much lower, while number of journals ismore » higher. In addition, nuclear physics results are mainly published in a limited number of journals, such as Physical Review C and Nuclear Physics A. In the present work, historic publication trends and averages have been extracted and analyzed using nuclear data mining techniques. Lastly, the results of this study and implications are discussed and conclusions presented.« less

Heavy-Ion Physics at a Fixed-Target Experiment Using the LHC Proton and Lead Beams (AFTER@LHC): Feasibility Studies for Quarkonium and Drell-Yan Production

NASA Astrophysics Data System (ADS)

Trzeciak, B.; Da Silva, C.; Ferreiro, E. G.; Hadjidakis, C.; Kikola, D.; Lansberg, J. P.; Massacrier, L.; Seixas, J.; Uras, A.; Yang, Z.

2017-09-01

We outline the case for heavy-ion-physics studies using the multi-TeV lead LHC beams in the fixed-target mode. After a brief contextual reminder, we detail the possible contributions of AFTER@LHC to heavy-ion physics with a specific emphasis on quarkonia. We then present performance simulations for a selection of observables. These show that Υ (nS), J/ψ and ψ (2S) production in heavy-ion collisions can be studied in new energy and rapidity domains with the LHCb and ALICE detectors. We also discuss the relevance to analyse the Drell-Yan pair production in asymmetric nucleus-nucleus collisions to study the factorisation of the nuclear modification of partonic densities and of further quarkonium states to restore their status of golden probes of the quark-gluon plasma formation.

Purification, characterization, and sequencing of antimicrobial peptides, Cy-AMP1, Cy-AMP2, and Cy-AMP3, from the Cycad (Cycas revoluta) seeds.

PubMed

Yokoyama, Seiya; Kato, Kouji; Koba, Atsuko; Minami, Yuji; Watanabe, Keiichi; Yagi, Fumio

2008-12-01

Novel antimicrobial peptides (AMP), designated Cy-AMP1, Cy-AMP2, and Cy-AMP3, were purified from seeds of the cycad (Cycas revoluta) by a CM cellulofine column, ion-exchange HPLC on SP COSMOGEL, and reverse-phase HPLC. They had molecular masses of 4583.2 Da, 4568.9 Da and 9275.8 Da, respectively, by MALDI-TOF MS analysis. Half of the amino acid residues of Cy-AMP1 and Cy-AMP2 were cysteine, glycine and proline, and their sequences were similar. The sequence of Cy-AMP3 showed high homology to various lipid transfer proteins. For Cy-AMP1 and Cy-AMP2, the concentrations of peptides required for 50% inhibition (IC(50)) of the growth of plant pathogenic fungi, Gram-positive and Gram-negative bacteria were 7.0-8.9 microg/ml. The Cy-AMP3 had weak antimicrobial activity. The structural and antimicrobial characteristics of Cy-AMP1 and Cy-AMP2 indicated that they are a novel type of antimicrobial peptide belonging to a plant defensin family.

Large-N Over the Source Physics Experiment (SPE) Phase I and Phase II Test Beds

NASA Astrophysics Data System (ADS)

Snelson, C. M.; Carmichael, J. D.; Mellors, R. J.; Abbott, R. E.

2014-12-01

One of the current challenges in the field of monitoring and verification is source discrimination of low-yield nuclear explosions from background seismicity, both natural and anthropogenic. Work is underway at the Nevada National Security Site to conduct a series of chemical explosion experiments using a multi-institutional, multi-disciplinary approach. The goal of this series of experiments, called the Source Physics Experiments (SPE), is to refine the understanding of the effect of earth structures on source phenomenology and energy partitioning in the source region, the transition of seismic energy from the near field to the far field, and the development of S waves observed in the far field. To fully explore these problems, the SPE series includes tests in both hard and soft rock geologic environments. The project comprises a number of activities, which range from characterizing the shallow subsurface to acquiring new explosion data from both the near field (<100 m) and the far field (>100 m). SPE includes a series of planned explosions (with different yields and depths of burials), which are conducted in the same hole and monitored by a diverse set of sensors recording characteristics of the explosions, ground-shock, seismo-acoustic energy propagation. This presentation focuses on imaging the full 3D wavefield over hard rock and soft rock test beds using a large number of seismic sensors. This overview presents statistical analyses of optimal sensor layout required to estimate wavefield discriminants and the planned deployment for the upcoming experiments. This work was conducted under Contract No. DE-AC52-06NA25946 with the U.S. Department of Energy. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Integrated Nuclear and Conventional Theater Warfare Simulation (INWARS) Level III Specifications. Volume III. Air Combat Modeling.

DTIC Science & Technology

1978-07-24

will include an implicit air function that will perform the air planning and requesting associated with the various headquarters. The decision structure...air headquarters (The ATAF/TAA) will be included in the CIC to perform the implementation of the decisions /goals of the C21 elements, 1-4...realistic fashion. Once the AMPs have been formed, the operational process of launching, mission implementation etc. is no longer keyed to the decision cycle

Fuel Performance Experiments and Modeling: Fission Gas Bubble Nucleation and Growth in Alloy Nuclear Fuels

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

McDeavitt, Sean; Shao, Lin; Tsvetkov, Pavel

2014-04-07

Advanced fast reactor systems being developed under the DOE's Advanced Fuel Cycle Initiative are designed to destroy TRU isotopes generated in existing and future nuclear energy systems. Over the past 40 years, multiple experiments and demonstrations have been completed using U-Zr, U-Pu-Zr, U-Mo and other metal alloys. As a result, multiple empirical and semi-empirical relationships have been established to develop empirical performance modeling codes. Many mechanistic questions about fission as mobility, bubble coalescience, and gas release have been answered through industrial experience, research, and empirical understanding. The advent of modern computational materials science, however, opens new doors of development suchmore » that physics-based multi-scale models may be developed to enable a new generation of predictive fuel performance codes that are not limited by empiricism.« less

Tandem accelerators in Romania: Multi-tools for science, education and technology

NASA Astrophysics Data System (ADS)

Burducea, I.; GhiÅ£ǎ, D. G.; Sava, T. B.; Straticiuc, M.

2017-06-01

An educated selection of the main beam parameters - particle type, velocity and intensity, can result in a cutting-edge scalpel to remove tumors, sanitize sewage, act as a nuclear forensics detective, date an artefact, clean up air, improve a microprocessor, transmute nuclear waste, detect a counterfeit or even look into the stars. Nowadays more than particle accelerators operate worldwide in medicine, industry and basic research. For example the proton therapy market is expected to attain 1 billion US per year in 2019 with almost 330 proton therapy rooms, while the annual market for the ion implantation industry already reached 1.5 G in revenue [1,2]. A brief history of the Tandem Accelerators Complex at IFIN-HH [3] emphasizing on their applications and the physics behind the scenes, is also presented [4-6].

Advanced Technology and Mitigation (ATDM) SPARC Re-Entry Code Fiscal Year 2017 Progress and Accomplishments for ECP.

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

Crozier, Paul; Howard, Micah; Rider, William J.

The SPARC (Sandia Parallel Aerodynamics and Reentry Code) will provide nuclear weapon qualification evidence for the random vibration and thermal environments created by re-entry of a warhead into the earth’s atmosphere. SPARC incorporates the innovative approaches of ATDM projects on several fronts including: effective harnessing of heterogeneous compute nodes using Kokkos, exascale-ready parallel scalability through asynchronous multi-tasking, uncertainty quantification through Sacado integration, implementation of state-of-the-art reentry physics and multiscale models, use of advanced verification and validation methods, and enabling of improved workflows for users. SPARC is being developed primarily for the Department of Energy nuclear weapon program, with additional developmentmore » and use of the code is being supported by the Department of Defense for conventional weapons programs.« less

2',3'-cAMP, 3'-AMP, 2'-AMP and adenosine inhibit TNF-α and CXCL10 production from activated primary murine microglia via A2A receptors.

PubMed

Newell, Elizabeth A; Exo, Jennifer L; Verrier, Jonathan D; Jackson, Travis C; Gillespie, Delbert G; Janesko-Feldman, Keri; Kochanek, Patrick M; Jackson, Edwin K

2015-01-12

Some cells, tissues and organs release 2',3'-cAMP (a positional isomer of 3',5'-cAMP) and convert extracellular 2',3'-cAMP to 2'-AMP plus 3'-AMP and convert these AMPs to adenosine (called the extracellular 2',3'-cAMP-adenosine pathway). Recent studies show that microglia have an extracellular 2',3'-cAMP-adenosine pathway. The goal of the present study was to investigate whether the extracellular 2',3'-cAMP-adenosine pathway could have functional consequences on the production of cytokines/chemokines by activated microglia. Experiments were conducted in cultures of primary murine microglia. In the first experiment, the effect of 2',3'-cAMP, 3'-AMP, 2'-AMP and adenosine on LPS-induced TNF-α and CXCL10 production was determined. In the next experiment, the first protocol was replicated but with the addition of 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX) (0.1 μM; antagonist of adenosine receptors). The last experiment compared the ability of 2-chloro-N(6)-cyclopentyladenosine (CCPA) (10 μM; selective A1 agonist), 5'-N-ethylcarboxamide adenosine (NECA) (10 μM; agonist for all adenosine receptor subtypes) and CGS21680 (10 μM; selective A2A agonist) to inhibit LPS-induced TNF-α and CXCL10 production. (1) 2',3'-cAMP, 3'-AMP, 2'-AMP and adenosine similarly inhibited LPS-induced TNF-α and CXCL10 production; (2) DPSPX nearly eliminated the inhibitory effects of 2',3'-cAMP, 3'-AMP, 2'-AMP and adenosine on LPS-induced TNF-α and CXCL10 production; (3) CCPA did not affect LPS-induced TNF-α and CXCL10; (4) NECA and CGS21680 similarly inhibited LPS-induced TNF-α and CXCL10 production. 2',3'-cAMP and its metabolites (3'-AMP, 2'-AMP and adenosine) inhibit LPS-induced TNF-α and CXCL10 production via A2A-receptor activation. Adenosine and its precursors, via A2A receptors, likely suppress TNF-α and CXCL10 production by activated microglia in brain diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration.

PubMed

Zhang, Li; He, Huamei; Balschi, James A

2007-07-01

AMP-activated protein kinase (AMPK) acts as a cellular energy sensor: it responds to an increase in AMP concentration ([AMP]) or the AMP-to-ATP ratio (AMP/ATP). Metformin and phenformin, which are biguanides, have been reported to increase AMPK activity without increasing AMP/ATP. This study tests the hypothesis that these biguanides increase AMPK activity in the heart by increasing cytosolic [AMP]. Groups of isolated rat hearts (n = 5-7 each) were perfused with Krebs-Henseleit buffer with or without 0.2 mM phenformin or 10 mM metformin, and (31)P-NMR-measured phosphocreatine, ATP, and intracellular pH were used to calculate cytosolic [AMP]. At various times, hearts were freeze-clamped and assayed for AMPK activity, phosphorylation of Thr(172) on AMPK-alpha, and phosphorylation of Ser(79) on acetyl-CoA carboxylase, an AMPK target. In hearts treated with phenformin for 18 min and then perfused for 20 min with Krebs-Henseleit buffer, [AMP] began to increase at 26 min and AMPK activity was elevated at 36 min. In hearts treated with metformin, [AMP] was increased at 50 min and AMPK activity, phosphorylated AMPK, and phosphorylated acetyl-CoA carboxylase were elevated at 61 min. In metformin-treated hearts, HPLC-measured total AMP content and total AMP/ATP did not increase. In summary, phenformin and metformin increase AMPK activity and phosphorylation in the isolated heart. The increase in AMPK activity was always preceded by and correlated with increased cytosolic [AMP]. Total AMP content and total AMP/ATP did not change. Cytosolic [AMP] reported metabolically active AMP, which triggered increased AMPK activity, but measures of total AMP did not.

Population Distribution of Beta-Lactamase Conferring Resistance to Third-Generation Cephalosporins in Human Clinical Enterobacteriaceae in The Netherlands

PubMed Central

Voets, Guido M.; Platteel, Tamara N.; Fluit, Ad C.; Scharringa, Jelle; Schapendonk, Claudia M.; Stuart, James Cohen; Bonten, Marc J. M.; Hall, Maurine A. L.

2012-01-01

There is a global increase in infections caused by Enterobacteriaceae with plasmid-borne β-lactamases that confer resistance to third-generation cephalosporins. The epidemiology of these bacteria is not well understood, and was, therefore, investigated in a selection of 636 clinical Enterobacteriaceae with a minimal inhibitory concentration >1 mg/L for ceftazidime/ceftriaxone from a national survey (75% E. coli, 11% E. cloacae, 11% K. pneumoniae, 2% K. oxytoca, 2% P. mirabilis). Isolates were investigated for extended-spectrum β-lactamases (ESBLs) and ampC genes using microarray, PCR, gene sequencing and molecular straintyping (Diversilab and multi-locus sequence typing (MLST)). ESBL genes were demonstrated in 512 isolates (81%); of which 446 (87%) belonged to the CTX-M family. Among 314 randomly selected and sequenced isolates, bla CTX-M-15 was most prevalent (n = 124, 39%), followed by bla CTX-M-1 (n = 47, 15%), bla CTX-M-14 (n = 15, 5%), bla SHV-12 (n = 24, 8%) and bla TEM-52 (n = 13, 4%). Among 181 isolates with MIC ≥16 mg/L for cefoxitin plasmid encoded AmpCs were detected in 32 and 27 were of the CMY-2 group. Among 102 E. coli isolates with MIC ≥16 mg/L for cefoxitin ampC promoter mutations were identified in 29 (28%). Based on Diversilab genotyping of 608 isolates (similarity cut-off >98%) discriminatory indices of bacteria with ESBL and/or ampC genes were 0.994, 0.985 and 0.994 for E. coli, K. pneumoniae and E. cloacae, respectively. Based on similarity cut-off >95% two large clusters of E. coli were apparent (of 43 and 30 isolates) and 21 of 21 that were typed by belonged to ST131 of which 13 contained bla CTX-M-15. Our findings demonstrate that bla CTX-M-15 is the most prevalent ESBL and we report a larger than previously reported prevalence of ampC genes among Enterobacteriaceae responsible for resistance to third-generation cephalosporins. PMID:23284886

Analysis of physics-based preconditioning for single-phase subchannel equations

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

Hansel, J. E.; Ragusa, J. C.; Allu, S.

2013-07-01

The (single-phase) subchannel approximations are used throughout nuclear engineering to provide an efficient flow simulation because the computational burden is much smaller than for computational fluid dynamics (CFD) simulations, and empirical relations have been developed and validated to provide accurate solutions in appropriate flow regimes. Here, the subchannel equations have been recast in a residual form suitable for a multi-physics framework. The Eigen spectrum of the Jacobian matrix, along with several potential physics-based preconditioning approaches, are evaluated, and the the potential for improved convergence from preconditioning is assessed. The physics-based preconditioner options include several forms of reduced equations that decouplemore » the subchannels by neglecting crossflow, conduction, and/or both turbulent momentum and energy exchange between subchannels. Eigen-scopy analysis shows that preconditioning moves clusters of eigenvalues away from zero and toward one. A test problem is run with and without preconditioning. Without preconditioning, the solution failed to converge using GMRES, but application of any of the preconditioners allowed the solution to converge. (authors)« less

Synergistic Activation of Steroidogenic Acute Regulatory Protein Expression and Steroid Biosynthesis by Retinoids: Involvement of cAMP/PKA Signaling

PubMed Central

Manna, Pulak R.; Slominski, Andrzej T.; King, Steven R.; Stetson, Cloyce L.

2014-01-01

Both retinoic acid receptors (RARs) and retinoid X receptors (RXRs) mediate the action of retinoids that play important roles in reproductive development and function, as well as steroidogenesis. Regulation of steroid biosynthesis is principally mediated by the steroidogenic acute regulatory protein (StAR); however, the modes of action of retinoids in the regulation of steroidogenesis remain obscure. In this study we demonstrate that all-trans retinoic acid (atRA) enhances StAR expression, but not its phosphorylation (P-StAR), and progesterone production in MA-10 mouse Leydig cells. Activation of the protein kinase A (PKA) cascade, by dibutyrl-cAMP or type I/II PKA analogs, markedly increased retinoid-responsive StAR, P-StAR, and steroid levels. Targeted silencing of endogenous RARα and RXRα, with small interfering RNAs, resulted in decreases in 9-cis RA-stimulated StAR and progesterone levels. Truncation of and mutational alterations in the 5′-flanking region of the StAR gene demonstrated the importance of the −254/−1-bp region in retinoid responsiveness. An oligonucleotide probe encompassing an RXR/liver X receptor recognition motif, located within the −254/−1-bp region, specifically bound MA-10 nuclear proteins and in vitro transcribed/translated RXRα and RARα in EMSAs. Transcription of the StAR gene in response to atRA and dibutyrl-cAMP was influenced by several factors, its up-regulation being dependent on phosphorylation of cAMP response-element binding protein (CREB). Chromatin immunoprecipitation studies revealed the association of phosphorylation of CREB, CREB binding protein, RXRα, and RARα to the StAR promoter. Further studies elucidated that hormone-sensitive lipase plays an important role in atRA-mediated regulation of the steroidogenic response that involves liver X receptor signaling. These findings delineate the molecular events by which retinoids influence cAMP/PKA signaling and provide additional and novel insight into the regulation of StAR expression and steroidogenesis in mouse Leydig cells. PMID:24265455

The glutamate carboxypeptidase AMP1 mediates abscisic acid and abiotic stress responses in Arabidopsis.

PubMed

Shi, Yiting; Wang, Zheng; Meng, Pei; Tian, Siqi; Zhang, Xiaoyan; Yang, Shuhua

2013-07-01

ALTERED MERISTEM PROGRAM1 (AMP1) encodes a glutamate carboxypeptidase that plays an important role in shoot apical meristem development and phytohormone homeostasis. We isolated a new mutant allele of AMP1, amp1-20, from a screen for abscisic acid (ABA) hypersensitive mutants and characterized the function of AMP1 in plant stress responses. amp1 mutants displayed ABA hypersensitivity, while overexpression of AMP1 caused ABA insensitivity. Moreover, endogenous ABA concentration was increased in amp1-20- and decreased in AMP1-overexpressing plants under stress conditions. Application of ABA reduced the AMP1 protein level in plants. Interestingly, amp1 mutants accumulated excess superoxide and displayed hypersensitivity to oxidative stress. The hypersensitivity of amp1 to ABA and oxidative stress was partially rescued by reactive oxygen species (ROS) scavenging agent. Furthermore, amp1 was tolerant to freezing and drought stress. The ABA hypersensitivity and freezing tolerance of amp1 was dependent on ABA signaling. Moreover, amp1 had elevated soluble sugar content and showed hypersensitivity to high concentrations of sugar. By contrast, the contents of amino acids were changed in amp1 mutant compared to the wild-type. This study suggests that AMP1 modulates ABA, oxidative and abotic stress responses, and is involved in carbon and amino acid metabolism in Arabidopsis. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Schwann Cells Metabolize Extracellular 2′,3′-cAMP to 2′-AMP

PubMed Central

Verrier, Jonathan D.; Kochanek, Patrick M.

2015-01-01

The 3′,5′-cAMP–adenosine pathway (3′,5′-cAMP→5′-AMP→adenosine) and the 2′,3′-cAMP–adenosine pathway (2′,3′-cAMP→2′-AMP/3′-AMP→adenosine) are active in the brain. Oligodendrocytes participate in the brain 2′,3′-cAMP–adenosine pathway via their robust expression of 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase; converts 2′,3′-cAMP to 2′-AMP). Because Schwann cells also express CNPase, it is conceivable that the 2′,3′-cAMP–adenosine pathway exists in the peripheral nervous system. To test this and to compare the 2′,3′-cAMP–adenosine pathway to the 3′,5′-cAMP–adenosine pathway in Schwann cells, we examined the metabolism of 2′,3′-cAMP, 2′-AMP, 3′-AMP, 3′,5′-cAMP, and 5′-AMP in primary rat Schwann cells in culture. Addition of 2′,3′-cAMP (3, 10, and 30 µM) to Schwann cells increased levels of 2′-AMP in the medium from 0.006 ± 0.002 to 21 ± 2, 70 ± 3, and 187 ± 10 nM/µg protein, respectively; in contrast, Schwann cells had little ability to convert 2′,3′-cAMP to 3′-AMP or 3′,5′-cAMP to either 3′-AMP or 5′-AMP. Although Schwann cells slightly converted 2′,3′-cAMP and 2′-AMP to adenosine, they did so at very modest rates (e.g., 5- and 3-fold, respectively, more slowly compared with our previously reported studies in oligodendrocytes). Using transected myelinated rat sciatic nerves in culture medium, we observed a time-related increase in endogenous intracellular 2′,3′-cAMP and extracellular 2′-AMP. These findings indicate that Schwann cells do not have a robust 3′,5′-cAMP–adenosine pathway but do have a 2′,3′-cAMP–adenosine pathway; however, because the pathway mostly involves 2′-AMP formation rather than 3′-AMP, and because the conversion of 2′-AMP to adenosine is slow, metabolism of 2′,3′-cAMP mostly results in the accumulation of 2′-AMP. Accumulation of 2′-AMP in peripheral nerves postinjury could have pathophysiological consequences. PMID:25998049

A Simple Photometer to Study Skylight

ERIC Educational Resources Information Center

McIntosh Gordon

2006-01-01

A simple photometer constructed from an LED and an op amp can be used to measure light in a number of physical situations. A variety of LEDs exist to investigate different wavelength ranges. Combined with an inexpensive transit, the LED photometer can be used to carry out skylight studies and atmospheric optical depth measurements. The activities…

Alternative Fuels Data Center: Methanol

Science.gov Websites

(CH3OH), also known as wood alcohol, is considered an alternative fuel under the Energy Policy Act of 1992. As an engine fuel, methanol has chemical and physical fuel properties similar to ethanol Ethanol Hydrogen Natural Gas Propane Emerging Fuels Fuel Prices Conserve Fuel Idle Reduction Parts &

AMPK Agonist AICAR Improves Cognition and Motor Coordination in Young and Aged Mice

ERIC Educational Resources Information Center

Kobilo, Tali; Guerrieri, Davide; Zhang, Yongqing; Collica, Sarah C.; Becker, Kevin G.; van Praag, Henriette

2014-01-01

Normal aging can result in a decline of memory and muscle function. Exercise may prevent or delay these changes. However, aging-associated frailty can preclude physical activity. In young sedentary animals, pharmacological activation of AMP-activated protein kinase (AMPK), a transcriptional regulator important for muscle physiology, enhanced…

Exchange protein directly activated by cAMP mediates slow delayed-rectifier current remodeling by sustained β-adrenergic activation in guinea pig hearts.

PubMed

Aflaki, Mona; Qi, Xiao-Yan; Xiao, Ling; Ordog, Balazs; Tadevosyan, Artavazd; Luo, Xiaobin; Maguy, Ange; Shi, Yanfen; Tardif, Jean-Claude; Nattel, Stanley

2014-03-14

β-Adrenoceptor activation contributes to sudden death risk in heart failure. Chronic β-adrenergic stimulation, as occurs in patients with heart failure, causes potentially arrhythmogenic reductions in slow delayed-rectifier K(+) current (IKs). To assess the molecular mechanisms of IKs downregulation caused by chronic β-adrenergic activation, particularly the role of exchange protein directly activated by cAMP (Epac). Isolated guinea pig left ventricular cardiomyocytes were incubated in primary culture and exposed to isoproterenol (1 μmol/L) or vehicle for 30 hours. Sustained isoproterenol exposure decreased IKs density (whole cell patch clamp) by 58% (P<0.0001), with corresponding decreases in potassium voltage-gated channel subfamily E member 1 (KCNE1) mRNA and membrane protein expression (by 45% and 51%, respectively). Potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) mRNA expression was unchanged. The β1-adrenoceptor antagonist 1-[2-((3-Carbamoyl-4-hydroxy)phenoxy)ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol dihydrochloride (CGP-20712A) prevented isoproterenol-induced IKs downregulation, whereas the β2-antagonist ICI-118551 had no effect. The selective Epac activator 8-pCPT-2'-O-Me-cAMP decreased IKs density to an extent similar to isoproterenol exposure, and adenoviral-mediated knockdown of Epac1 prevented isoproterenol-induced IKs/KCNE1 downregulation. In contrast, protein kinase A inhibition with a cell-permeable highly selective peptide blocker did not affect IKs downregulation. 1,2-Bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetate-AM acetoxymethyl ester (BAPTA-AM), cyclosporine, and inhibitor of nuclear factor of activated T cell (NFAT)-calcineurin association-6 (INCA6) prevented IKs reduction by isoproterenol and INCA6 suppressed isoproterenol-induced KCNE1 downregulation, consistent with signal-transduction via the Ca(2+)/calcineurin/NFAT pathway. Isoproterenol induced nuclear NFATc3/c4 translocation (immunofluorescence), which was suppressed by Epac1 knockdown. Chronic in vivo administration of isoproterenol to guinea pigs reduced IKs density and KCNE1 mRNA and protein expression while inducing cardiac dysfunction and action potential prolongation. Selective in vivo activation of Epac via sp-8-pCPT-2'-O-Me-cAMP infusion decreased IKs density and KCNE1 mRNA/protein expression. Prolonged β1-adrenoceptor stimulation suppresses IKs by downregulating KCNE1 mRNA and protein via Epac-mediated Ca(2+)/calcineurin/NFAT signaling. These results provide new insights into the molecular basis of K(+) channel remodeling under sustained adrenergic stimulation.

Pressure Sensing with Fiber Optics and Interferometry.

DTIC Science & Technology

1980-12-01

equation yields the interference term of interest (I,2) as shown. 1 2 > = I + 12 + 1 (Eq. 2.2) where I 1 < E2 > ’ = < 2 > 12=< El EP. > t+T E Taking the...is associated with the P’ZT control loop. Laser & Supply, Spectra Physics Model 142........ ..... . ... 1 ea High Voltage DC Op-Amp, Burleigh PZ.-70...The following equipment is associated with the A/O control loop. Modified Laser Exciter, Spectra Physics Model 132 .. ...... 1 Gain Tube, Jodon cf

High-fidelity projective read-out of a solid-state spin quantum register.

PubMed

Robledo, Lucio; Childress, Lilian; Bernien, Hannes; Hensen, Bas; Alkemade, Paul F A; Hanson, Ronald

2011-09-21

Initialization and read-out of coupled quantum systems are essential ingredients for the implementation of quantum algorithms. Single-shot read-out of the state of a multi-quantum-bit (multi-qubit) register would allow direct investigation of quantum correlations (entanglement), and would give access to further key resources such as quantum error correction and deterministic quantum teleportation. Although spins in solids are attractive candidates for scalable quantum information processing, their single-shot detection has been achieved only for isolated qubits. Here we demonstrate the preparation and measurement of a multi-spin quantum register in a low-temperature solid-state system by implementing resonant optical excitation techniques originally developed in atomic physics. We achieve high-fidelity read-out of the electronic spin associated with a single nitrogen-vacancy centre in diamond, and use this read-out to project up to three nearby nuclear spin qubits onto a well-defined state. Conversely, we can distinguish the state of the nuclear spins in a single shot by mapping it onto, and subsequently measuring, the electronic spin. Finally, we show compatibility with qubit control: we demonstrate initialization, coherent manipulation and single-shot read-out in a single experiment on a two-qubit register, using techniques suitable for extension to larger registers. These results pave the way for a test of Bell's inequalities on solid-state spins and the implementation of measurement-based quantum information protocols. © 2011 Macmillan Publishers Limited. All rights reserved

Multi-Organization Multi-Discipline Effort Developing a Mitigation Concept for Planetary Defense

NASA Technical Reports Server (NTRS)

Leung, Ronald Y.; Barbee, Brent W.; Seery, Bernard D.; Bambacus, Myra; Finewood, Lee; Greenaugh, Kevin C.; Lewis, Anthony; Dearborn, David; Miller, Paul L.; Weaver, Robert P.;

Heavy ion linear accelerator for radiation damage studies of materials

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

Kutsaev, Sergey V.; Mustapha, Brahim; Ostroumov, Peter N.

A new eXtreme MATerial (XMAT) research facility is being proposed at Argonne National Laboratory to enable rapid in situ mesoscale bulk analysis of ion radiation damage in advanced materials and nuclear fuels. This facility combines a new heavy-ion accelerator with the existing high-energy X-ray analysis capability of the Argonne Advanced Photon Source. The heavy-ion accelerator and target complex will enable experimenters to emulate the environment of a nuclear reactor making possible the study of fission fragment damage in materials. Material scientists will be able to use the measured material parameters to validate computer simulation codes and extrapolate the response ofmore » the material in a nuclear reactor environment. Utilizing a new heavy-ion accelerator will provide the appropriate energies and intensities to study these effects with beam intensities which allow experiments to run over hours or days instead of years. The XMAT facility will use a CW heavy-ion accelerator capable of providing beams of any stable isotope with adjustable energy up to 1.2 MeV/u for U-238(50+) and 1.7 MeV for protons. This energy is crucial to the design since it well mimics fission fragments that provide the major portion of the damage in nuclear fuels. The energy also allows damage to be created far from the surface of the material allowing bulk radiation damage effects to be investigated. The XMAT ion linac includes an electron cyclotron resonance ion source, a normal-conducting radio-frequency quadrupole and four normal-conducting multi-gap quarter-wave resonators operating at 60.625 MHz. This paper presents the 3D multi-physics design and analysis of the accelerating structures and beam dynamics studies of the linac.« less

Heavy ion linear accelerator for radiation damage studies of materials

NASA Astrophysics Data System (ADS)

Kutsaev, Sergey V.; Mustapha, Brahim; Ostroumov, Peter N.; Nolen, Jerry; Barcikowski, Albert; Pellin, Michael; Yacout, Abdellatif

2017-03-01

A new eXtreme MATerial (XMAT) research facility is being proposed at Argonne National Laboratory to enable rapid in situ mesoscale bulk analysis of ion radiation damage in advanced materials and nuclear fuels. This facility combines a new heavy-ion accelerator with the existing high-energy X-ray analysis capability of the Argonne Advanced Photon Source. The heavy-ion accelerator and target complex will enable experimenters to emulate the environment of a nuclear reactor making possible the study of fission fragment damage in materials. Material scientists will be able to use the measured material parameters to validate computer simulation codes and extrapolate the response of the material in a nuclear reactor environment. Utilizing a new heavy-ion accelerator will provide the appropriate energies and intensities to study these effects with beam intensities which allow experiments to run over hours or days instead of years. The XMAT facility will use a CW heavy-ion accelerator capable of providing beams of any stable isotope with adjustable energy up to 1.2 MeV/u for 238U50+ and 1.7 MeV for protons. This energy is crucial to the design since it well mimics fission fragments that provide the major portion of the damage in nuclear fuels. The energy also allows damage to be created far from the surface of the material allowing bulk radiation damage effects to be investigated. The XMAT ion linac includes an electron cyclotron resonance ion source, a normal-conducting radio-frequency quadrupole and four normal-conducting multi-gap quarter-wave resonators operating at 60.625 MHz. This paper presents the 3D multi-physics design and analysis of the accelerating structures and beam dynamics studies of the linac.

The Nuclear Energy Density Functional Formalism

NASA Astrophysics Data System (ADS)

Duguet, T.

The present document focuses on the theoretical foundations of the nuclear energy density functional (EDF) method. As such, it does not aim at reviewing the status of the field, at covering all possible ramifications of the approach or at presenting recent achievements and applications. The objective is to provide a modern account of the nuclear EDF formalism that is at variance with traditional presentations that rely, at one point or another, on a Hamiltonian-based picture. The latter is not general enough to encompass what the nuclear EDF method represents as of today. Specifically, the traditional Hamiltonian-based picture does not allow one to grasp the difficulties associated with the fact that currently available parametrizations of the energy kernel E[g',g] at play in the method do not derive from a genuine Hamilton operator, would the latter be effective. The method is formulated from the outset through the most general multi-reference, i.e. beyond mean-field, implementation such that the single-reference, i.e. "mean-field", derives as a particular case. As such, a key point of the presentation provided here is to demonstrate that the multi-reference EDF method can indeed be formulated in a mathematically meaningful fashion even if E[g',g] does not derive from a genuine Hamilton operator. In particular, the restoration of symmetries can be entirely formulated without making any reference to a projected state, i.e. within a genuine EDF framework. However, and as is illustrated in the present document, a mathematically meaningful formulation does not guarantee that the formalism is sound from a physical standpoint. The price at which the latter can be enforced as well in the future is eventually alluded to.

Role of CNPase in the Oligodendrocytic Extracellular 2′,3′-cAMP-Adenosine Pathway

PubMed Central

Verrier, Jonathan D.; Jackson, Travis C.; Gillespie, Delbert G.; Janesko-Feldman, Keri; Bansal, Rashmi; Goebbels, Sandra; Nave, Klaus-Armin; Kochanek, Patrick M.; Jackson, Edwin K.

2014-01-01

Extracellular adenosine 3′,5′-cyclic monophosphate (3′,5′-cAMP) is an endogenous source of localized adenosine production in many organs. Recent studies suggest that extracellular 2′,3′-cAMP (positional isomer of 3′,5′-cAMP) is also a source of adenosine, particularly in the brain in vivo post-injury. Moreover, in vitro studies show that both microglia and astrocytes can convert extracellular 2′,3′-cAMP to adenosine. Here we examined the ability of primary mouse oligodendrocytes and neurons to metabolize extracellular 2′,3′-cAMP and their respective adenosine monophosphates (2′-AMP and 3′-AMP). Cells were also isolated from mice deficient in 2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNPase). Oligodendrocytes metabolized 2′,3′-cAMP to 2′-AMP with 10-fold greater efficiency than did neurons (and also more than previously examined microglia and astrocytes); whereas, the production of 3′-AMP was minimal in both oligodendrocytes and neurons. The production of 2′-AMP from 2′,3′-cAMP was reduced by 65% in CNPase -/- versus CNPase +/+ oligodendrocytes. Oligodendrocytes also converted 2′-AMP to adenosine, and this was also attenuated in CNPase -/- oligodendrocytes. Inhibition of classic 3′,5′-cAMP-3′-phosphodiesterases with 3-isobutyl-1-methylxanthine did not block metabolism of 2′,3′-cAMP to 2′-AMP and inhibition of classic ecto-5′-nucleotidase (CD73) with α,β-methylene-adenosine-5′-diphosphate did not attenuate the conversion of 2′-AMP to adenosine. These studies demonstrate that oligodendrocytes express the extracellular 2′,3′-cAMP-adenosine pathway (2′,3′-cAMP → 2′-AMP → adenosine). This pathway is more robustly expressed in oligodendrocytes than in all other CNS cell types because CNPase is the predominant enzyme that metabolizes 2′,3′-cAMP to 2-AMP in CNS cells. By reducing levels of 2′,3′-cAMP (a mitochondrial toxin) and increasing levels of adenosine (a neuroprotectant), oligodendrocytes may protect axons from injury. PMID:23922219

2’,3’-cAMP, 3’-AMP, 2’-AMP and Adenosine Inhibit TNF-α and CXCL10 Production From Activated Primary Murine Microglia via A2A Receptors

PubMed Central

Newell, Elizabeth A.; Exo, Jennifer L.; Verrier, Jonathan D.; Jackson, Travis C.; Gillespie, Delbert G.; Janesko-Feldman, Keri; Kochanek, Patrick M.

2014-01-01

Background Some cells, tissues and organs release 2’,3’-cAMP (a positional isomer of 3’,5’-cAMP) and convert extracellular 2’,3’-cAMP to 2’-AMP plus 3’-AMP and convert these AMPs to adenosine (called the extracellular 2’,3’-cAMP-adenosine pathway). Recent studies show that microglia have an extracellular 2’,3’-cAMP-adenosine pathway. The goal of the present study was to investigate whether the extracellular 2’,3’-cAMP-adenosine pathway could have functional consequences on the production of cytokines/chemokines by activated microglia. Methods Experiments were conducted in cultures of primary murine microglia. In the first experiment, the effect of 2’,3’-cAMP, 3’-AMP, 2’-AMP and adenosine on LPS-induced TNF-α and CXCL10 production was determined. In the next experiment, the first protocol was replicated but with the addition of 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX) (0.1 µM; antagonist of adenosine receptors). The last experiment compared the ability of 2-chloro-N6-cyclopentyladenosine (CCPA) (10 µM; selective A1 agonist), 5’-N-ethylcarboxamide adenosine (NECA) (10 µM; agonist for all adenosine receptor subtypes) and CGS21680 (10 µM; selective A2A agonist) to inhibit LPS-induced TNF-α and CXCL10 production. Results 1) 2’,3’-cAMP, 3’-AMP, 2’-AMP and adenosine similarly inhibited LPS-induced TNF-α and CXCL10 production; 2) DPSPX nearly eliminated the inhibitory effects of 2’,3’-cAMP, 3’-AMP, 2’-AMP and adenosine on LPS-induced TNF-α and CXCL10 production; 3) CCPA did not affect LPS-induced TNF-α and CXCL10; 4) NECA and CGS21680 similarly inhibited LPS-induced TNF-α and CXCL10 production. Conclusions 2’,3’-cAMP and its metabolites (3’-AMP, 2’-AMP and adenosine) inhibit LPS-induced TNF-α and CXCL10 production via A2A-receptor activation. Adenosine and its precursors, via A2A receptors, likely suppress TNF-α and CXCL10 production by activated microglia in brain diseases. PMID:25451117

Progress and challenges in the development of physically-based numerical models for prediction of flow and contaminant dispersion in the urban environment

NASA Astrophysics Data System (ADS)

Lien, F. S.; Yee, E.; Ji, H.; Keats, A.; Hsieh, K. J.

2006-06-01

The release of chemical, biological, radiological, or nuclear (CBRN) agents by terrorists or rogue states in a North American city (densely populated urban centre) and the subsequent exposure, deposition and contamination are emerging threats in an uncertain world. The modeling of the transport, dispersion, deposition and fate of a CBRN agent released in an urban environment is an extremely complex problem that encompasses potentially multiple space and time scales. The availability of high-fidelity, time-dependent models for the prediction of a CBRN agent's movement and fate in a complex urban environment can provide the strongest technical and scientific foundation for support of Canada's more broadly based effort at advancing counter-terrorism planning and operational capabilities.The objective of this paper is to report the progress of developing and validating an integrated, state-of-the-art, high-fidelity multi-scale, multi-physics modeling system for the accurate and efficient prediction of urban flow and dispersion of CBRN (and other toxic) materials discharged into these flows. Development of this proposed multi-scale modeling system will provide the real-time modeling and simulation tool required to predict injuries, casualties and contamination and to make relevant decisions (based on the strongest technical and scientific foundations) in order to minimize the consequences of a CBRN incident in a populated centre.

Development of Regulatory Documents for Creation (Upgrade) of Physical Protection Systems under the Russian/American MPC&A Program

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

Izmaylov, Alexandr V.; Babkin, Vladimir; Kurov, Valeriy

2009-10-07

The development of new or the upgrade of existing physical protection systems (PPS) for nuclear facilities involves a multi-step and multidimensional process. The process consists of conceptual design, design, and commissioning stages. The activities associated with each of these stages are governed by Russian government and agency regulations. To ensure a uniform approach to development or upgrading of PPS at Russian nuclear facilities, the development of a range of regulatory and methodological documents is necessary. Some issues of PPS development are covered by the regulatory documents developed by Rosatom, as well as other Russian agencies with nuclear facilities under theirmore » control. This regulatory development has been accomplished as part of the U.S.-Russian MPC&A cooperation or independently by the Russian Federation. While regulatory coverage is extensive, there are a number of issues such as vulnerability analysis, effectiveness assessment, upgrading PPS, and protection of information systems for PPS that require additional regulations be developed. This paper reports on the status of regulatory coverage for PPS development or upgrade, and outlines a new approach to regulatory document development. It describes the evolutionary process of regulatory development through experience gained in the design, development and implementation of PPS as well as experience gained through the cooperative efforts of Russian and U.S. experts involved the development of MPC&A regulations.« less

Physics through the 1990s: Nuclear physics

NASA Technical Reports Server (NTRS)

1986-01-01

The volume begins with a non-mathematical introduction to nuclear physics. A description of the major advances in the field follows, with chapters on nuclear structure and dynamics, fundamental forces in the nucleus, and nuclei under extreme conditions of temperature, density, and spin. Impacts of nuclear physics on astrophysics and the scientific and societal benefits of nuclear physics are then discussed. Another section deals with scientific frontiers, describing research into the realm of the quark-gluon plasma; the changing description of nuclear matter, specifically the use of the quark model; and the implications of the standard model and grand unified theories of elementary-particle physics; and finishes with recommendations and priorities for nuclear physics research facilities, instrumentation, accelerators, theory, education, and data bases. Appended are a list of national accelerator facilities, a list of reviewers, a bibliography, and a glossary.

Dynamic chromosomal rearrangements in Hodgkin's lymphoma are due to ongoing three-dimensional nuclear remodeling and breakage-bridge-fusion cycles.

PubMed

Guffei, Amanda; Sarkar, Rahul; Klewes, Ludger; Righolt, Christiaan; Knecht, Hans; Mai, Sabine

2010-12-01

Hodgkin's lymphoma is characterized by the presence of mono-nucleated Hodgkin cells and bi- to multi-nucleated Reed-Sternberg cells. We have recently shown telomere dysfunction and aberrant synchronous/asynchronous cell divisions during the transition of Hodgkin cells to Reed-Sternberg cells.1 To determine whether overall changes in nuclear architecture affect genomic instability during the transition of Hodgkin cells to Reed-Sternberg cells, we investigated the nuclear organization of chromosomes in these cells. Three-dimensional fluorescent in situ hybridization revealed irregular nuclear positioning of individual chromosomes in Hodgkin cells and, more so, in Reed-Sternberg cells. We characterized an increasingly unequal distribution of chromosomes as mono-nucleated cells became multi-nucleated cells, some of which also contained chromosome-poor 'ghost' cell nuclei. Measurements of nuclear chromosome positions suggested chromosome overlaps in both types of cells. Spectral karyotyping then revealed both aneuploidy and complex chromosomal rearrangements: multiple breakage-bridge-fusion cycles were at the origin of the multiple rearranged chromosomes. This conclusion was challenged by super resolution three-dimensional structured illumination imaging of Hodgkin and Reed-Sternberg nuclei. Three-dimensional super resolution microscopy data documented inter-nuclear DNA bridges in multi-nucleated cells but not in mono-nucleated cells. These bridges consisted of chromatids and chromosomes shared by two Reed-Sternberg nuclei. The complexity of chromosomal rearrangements increased as Hodgkin cells developed into multi-nucleated cells, thus indicating tumor progression and evolution in Hodgkin's lymphoma, with Reed-Sternberg cells representing the highest complexity in chromosomal rearrangements in this disease. This is the first study to demonstrate nuclear remodeling and associated genomic instability leading to the generation of Reed-Sternberg cells of Hodgkin's lymphoma. We defined nuclear remodeling as a key feature of Hodgkin's lymphoma, highlighting the relevance of nuclear architecture in cancer.

Chitosan nanoparticles for the linear release of model cationic Peptide.

PubMed

Piras, Anna Maria; Sandreschi, Stefania; Maisetta, Giuseppantonio; Esin, Semih; Batoni, Giovanna; Chiellini, Federica

2015-07-01

The present study is focused on the development of a model drug delivery system (DDS) based on Chitosan (CS) nanoparticles using Renin substrate I (RSI) as model agent. RSI shares the main chemical-physical features of several biologically active antimicrobial peptides (AMPs). AMPs have a great therapeutic potential that is hampered by their lability in the biological fluids and as such they are perfect candidates for DDS. The development studies of quality DDS loaded with AMPs would require highly sensitive and specific quantification assays. The use of RSI allowed for the fine-tuning and optimization of the formulation parameters to promote the hydrophobic interactions between CS and the cationic peptide, favour the loading of the active ingredient and enhance the release properties of the carrier. RSI was encapsulated in chitosan NPs by mean of ionic gelation and a chromogenic enzymatic essay was carried out for the release kinetics evaluation. The developed formulations displayed almost 100% of encapsulation efficacy, low burst percentages, and a linear release of the model peptide. A release model was created showing a direct dependence on both the amount of RSI and NPs radius. Although CS has always been formulated with negatively charged active agents (e.g. oligonucleotides or anionic proteins), the use of ionotropic gelation in presence of a small cationic active agent promoted the formation of "core-shell" NPs. The described model, with tuneable linear release rates, appears eligible for further exploitation such as the loading of therapeutically active AMPs.

Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor

PubMed Central

Görner, Wolfram; Durchschlag, Erich; Wolf, Julia; Brown, Elizabeth L.; Ammerer, Gustav; Ruis, Helmut; Schüller, Christoph

2002-01-01

In yeast, environmental conditions control the transcription factor Msn2, the nuclear accumulation and function of which serve as a sensitive indicator of nutrient availablity and environmental stress load. We show here that the nuclear localization signal (NLS) of Msn2 is a direct target of cAMP-dependent protein kinase (cAPK). Genetic analysis suggests that Msn2-NLS function is inhibited by phosphorylation and activated by dephosphorylation. Msn2-NLS function is unaffected by many stress conditions that normally induce nuclear accumulation of full-length Msn2. The Msn2-NLS phosphorylation status is, however, highly sensitive to carbohydrate fluctuations during fermentative growth. Dephosphorylation occurs in >2 min after glucose withdrawal but the effect is reversed rapidly by refeeding with glucose. This response to glucose depletion is due to changes in cAPK activity rather than an increase in protein phosphatase activity. Surprisingly, the classical glucose-sensing systems are not connected to this rapid response system. Our results further imply that generic stress signals do not cause short-term depressions in cAPK activity. They operate on Msn2 by affecting an Msn5-dependent nuclear export and/or retention mechanism. PMID:11782433

Solubility of carbon dioxide in aqueous solutions of 2-amino-2-methyl-1-propanol and N-methyldiethanolamine and their mixtures in the temperature range of 313 to 353 K and pressures up to 2.7 MPa

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

Silkenbaeumer, D.; Lichtenthaler, R.N.; Rumpf, B.

1998-08-01

The solubility of carbon dioxide in aqueous solutions containing 2-amino-2-methyl-1-propanol (AMP) was measured in the temperature range from 313 to 353 K at total pressures up to 2.7 MPa using an analytical method. A model taking into account chemical reactions in the liquid phase as well as physical interactions is used to correlate the new data. To test the predictive capability of the model, the solubility of carbon dioxide in an aqueous solution containing AMP and N-methyldiethanolamine (MDEA) was measured at 313 K. Experimental results are reported and compared to literature data and calculations.

Dietary effects of adenosine monophosphate to enhance growth, digestibility, innate immune responses and stress resistance of juvenile red sea bream, Pagrus major.

PubMed

Hossain, Md Sakhawat; Koshio, Shunsuke; Ishikawa, Manabu; Yokoyama, Saichiro; Sony, Nadia Mahjabin

2016-09-01

Our study explored the dietary effects of adenosine monophosphate (AMP) to enhance growth, digestibility, innate immune responses and stress resistance of juvenile red sea bream. A semi-purified basal diet supplemented with 0% (Control), 0.1% (AMP-0.1), 0.2% (AMP-0.2), 0.4% (AMP-0.4) and 0.8% (AMP-0.8) purified AMP to formulate five experimental diets. Each diet was randomly allocated to triplicate groups of fish (mean initial weight 3.4 g) for 56 days. The results indicated that dietary AMP supplements tended to improve growth performances. One of the best ones was found in diet group AMP-0.2, followed by diet groups AMP-0.1, AMP-0.4 and AMP-0.8. The Apparent digestibility coefficients (dry matter, protein and lipid) also improved by AMP supplementation and the significantly highest dry matter digestibility was observed in diet group AMP-0.2. Fish fed diet groups AMP-0.2 and AMP-0.4 had significantly higher peroxidase and bactericidal activities than fish fed the control diet. Nitro-blue-tetrazolium (NBT) activity was found to be significantly (P < 0.05) greater in fish fed diet groups AMP-0.4 and AMP-0.8. Total serum protein, lysozyme activity and agglutination antibody titer were also increased (P > 0.05) by dietary supplementation. In contrast, catalase activity decreased with AMP supplementation. Moreover, the fish fed AMP supplemented diets had better improvement (P < 0.05) in body lipid contents, condition factor, hematocrit content and glutamyl oxaloacetic transaminase (GOT) level than the control group. Supplementation also improved both freshwater and oxidative stress resistances. Interestingly, the fish fed diet groups AMP-0.2 and AMP-0.4 showed the least oxidative stress condition. Finally it is concluded that, dietary AMP supplementation enhanced the growth, digestibility, immune response and stress resistance of red sea bream. The regression analysis revealed that a dietary AMP supplementation between 0.2 and 0.4% supported weight gain and lysozyme activity as a marker of immune functions for red sea bream, which is also inline with the most of the growth and health performance parameters of fish under present experimental conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

High Performances of Artificial Nacre-Like Graphene Oxide-Carrageenan Bio-Nanocomposite Films.

PubMed

Zhu, Wenkun; Chen, Tao; Li, Yi; Lei, Jia; Chen, Xin; Yao, Weitang; Duan, Tao

2017-05-16

This study was inspired by the unique multi-scale and multi-level 'brick-and-mortar' (B&M) structure of nacre layers. We prepared the B&M, environmentally-friendly graphene oxide-carrageenan (GO-Car) nanocomposite films using the following steps. A natural polyhydroxy polymer, carrageenan, was absorbed on the surface of monolayer GO nanosheets through hydrogen-bond interactions. Following this, a GO-Car hybridized film was produced through a natural drying process. We conducted structural characterization in addition to analyzing mechanical properties and cytotoxicity of the films. Scanning electron microscope (SEM) and X-ray diffraction (XRD) analyses showed that the nanocomposite films had a similar morphology and structure to nacre. Furthermore, the results from Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and Thermogravimetric (TG/DTG) were used to explain the GO-Car interaction. Analysis from static mechanical testers showed that GO-Car had enhanced Young's modulus, maximum tensile strength and breaking elongation compared to pure GO. The GO-Car nanocomposite films, containing 5% wt. of Car, was able to reach a tensile strength of 117 MPa. The biocompatibility was demonstrated using a RAW264.7 cell test, with no significant alteration found in cellular morphology and cytotoxicity. The preparation process for GO-Car films is simple and requires little time, with GO-Car films also having favorable biocompatibility and mechanical properties. These advantages make GO-Car nanocomposite films promising materials in replacing traditional petroleum-based plastics and tissue engineering-oriented support materials.

Functional characterization of the human phosphodiesterase 7A1 promoter.

PubMed Central

Torras-Llort, Mònica; Azorín, Fernando

2003-01-01

In this paper, the human phosphodiesterase 7A1 (h PDE7A1 ) promoter region was identified and functionally characterized. Transient transfection experiments indicated that a 2.9 kb fragment of the h PDE7A1 5'-flanking region, to position -2907, has strong promoter activity in Jurkat T-cells. Deletion analysis showed that the proximal region, up to position -988, contains major cis -regulatory elements of the h PDE7A1 promoter. This minimal promoter region contains a regulatory CpG island which is essential for promoter activity. The CpG island contains three potential cAMP-response-element-binding protein (CREB)-binding sites that, as judged by in vivo dimethyl sulphate (DMS) footprinting, are occupied in Jurkat T-cells. Moreover, over-expression of CREB results in increased promoter activity, but, on the other hand, promoter activity decreases when a dominant-negative form of CREB (KCREB) is over-expressed. In vivo DMS footprinting strongly indicates that other transcription factors, such Ets-2, nuclear factor of activated T-cells 1 (NFAT-1) and nuclear factor kappaB (NF-kappaB), might also contribute to the regulation of h PDE7A1 promoter. Finally, h PDE7A1 promoter was found to be induced by treatment with PMA, but not by treatment with dibutyryl cAMP or forskolin. These results provide insights into the factors and mechanisms that regulate expression of the h PDE7A gene. PMID:12737631

Basic Research Needs for Advanced Nuclear Systems. Report of the Basic Energy Sciences Workshop on Basic Research Needs for Advanced Nuclear Energy Systems, July 31-August 3, 2006

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

Roberto, J.; Diaz de la Rubia, T.; Gibala, R.

2006-10-01

The global utilization of nuclear energy has come a long way from its humble beginnings in the first sustained nuclear reaction at the University of Chicago in 1942. Today, there are over 440 nuclear reactors in 31 countries producing approximately 16% of the electrical energy used worldwide. In the United States, 104 nuclear reactors currently provide 19% of electrical energy used nationally. The International Atomic Energy Agency projects significant growth in the utilization of nuclear power over the next several decades due to increasing demand for energy and environmental concerns related to emissions from fossil plants. There are 28 newmore » nuclear plants currently under construction including 10 in China, 8 in India, and 4 in Russia. In the United States, there have been notifications to the Nuclear Regulatory Commission of intentions to apply for combined construction and operating licenses for 27 new units over the next decade. The projected growth in nuclear power has focused increasing attention on issues related to the permanent disposal of nuclear waste, the proliferation of nuclear weapons technologies and materials, and the sustainability of a once-through nuclear fuel cycle. In addition, the effective utilization of nuclear power will require continued improvements in nuclear technology, particularly related to safety and efficiency. In all of these areas, the performance of materials and chemical processes under extreme conditions is a limiting factor. The related basic research challenges represent some of the most demanding tests of our fundamental understanding of materials science and chemistry, and they provide significant opportunities for advancing basic science with broad impacts for nuclear reactor materials, fuels, waste forms, and separations techniques. Of particular importance is the role that new nanoscale characterization and computational tools can play in addressing these challenges. These tools, which include DOE synchrotron X-ray sources, neutron sources, nanoscale science research centers, and supercomputers, offer the opportunity to transform and accelerate the fundamental materials and chemical sciences that underpin technology development for advanced nuclear energy systems. The fundamental challenge is to understand and control chemical and physical phenomena in multi-component systems from femto-seconds to millennia, at temperatures to 1000?C, and for radiation doses to hundreds of displacements per atom (dpa). This is a scientific challenge of enormous proportions, with broad implications in the materials science and chemistry of complex systems. New understanding is required for microstructural evolution and phase stability under relevant chemical and physical conditions, chemistry and structural evolution at interfaces, chemical behavior of actinide and fission-product solutions, and nuclear and thermomechanical phenomena in fuels and waste forms. First-principles approaches are needed to describe f-electron systems, design molecules for separations, and explain materials failure mechanisms. Nanoscale synthesis and characterization methods are needed to understand and design materials and interfaces with radiation, temperature, and corrosion resistance. Dynamical measurements are required to understand fundamental physical and chemical phenomena. New multiscale approaches are needed to integrate this knowledge into accurate models of relevant phenomena and complex systems across multiple length and time scales.« less

A multi-state trajectory method for non-adiabatic dynamics simulations

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

Tao, Guohua, E-mail: taogh@pkusz.edu.cn

2016-03-07

A multi-state trajectory approach is proposed to describe nuclear-electron coupled dynamics in nonadiabatic simulations. In this approach, each electronic state is associated with an individual trajectory, among which electronic transition occurs. The set of these individual trajectories constitutes a multi-state trajectory, and nuclear dynamics is described by one of these individual trajectories as the system is on the corresponding state. The total nuclear-electron coupled dynamics is obtained from the ensemble average of the multi-state trajectories. A variety of benchmark systems such as the spin-boson system have been tested and the results generated using the quasi-classical version of the method showmore » reasonably good agreement with the exact quantum calculations. Featured in a clear multi-state picture, high efficiency, and excellent numerical stability, the proposed method may have advantages in being implemented to realistic complex molecular systems, and it could be straightforwardly applied to general nonadiabatic dynamics involving multiple states.« less

Chromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPARα.

PubMed

Ratman, Dariusz; Mylka, Viacheslav; Bougarne, Nadia; Pawlak, Michal; Caron, Sandrine; Hennuyer, Nathalie; Paumelle, Réjane; De Cauwer, Lode; Thommis, Jonathan; Rider, Mark H; Libert, Claude; Lievens, Sam; Tavernier, Jan; Staels, Bart; De Bosscher, Karolien

2016-12-15

Adaptation to fasting involves both Glucocorticoid Receptor (GRα) and Peroxisome Proliferator-Activated Receptor α (PPARα) activation. Given both receptors can physically interact we investigated the possibility of a genome-wide cross-talk between activated GR and PPARα, using ChIP- and RNA-seq in primary hepatocytes. Our data reveal extensive chromatin co-localization of both factors with cooperative induction of genes controlling lipid/glucose metabolism. Key GR/PPAR co-controlled genes switched from transcriptional antagonism to cooperativity when moving from short to prolonged hepatocyte fasting, a phenomenon coinciding with gene promoter recruitment of phosphorylated AMP-activated protein kinase (AMPK) and blocked by its pharmacological inhibition. In vitro interaction studies support trimeric complex formation between GR, PPARα and phospho-AMPK. Long-term fasting in mice showed enhanced phosphorylation of liver AMPK and GRα Ser211. Phospho-AMPK chromatin recruitment at liver target genes, observed upon prolonged fasting in mice, is dampened by refeeding. Taken together, our results identify phospho-AMPK as a molecular switch able to cooperate with nuclear receptors at the chromatin level and reveal a novel adaptation mechanism to prolonged fasting. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

1986 Nuclear Science Symposium, 33rd, and 1986 Symposium on Nuclear Power Systems, 18th, Washington, DC, Oct. 29-31, 1986, Proceedings

NASA Technical Reports Server (NTRS)

Stubblefield, F. W. (Editor)

1987-01-01

Papers are presented on space, low-energy physics, and general nuclear science instrumentations. Topics discussed include data acquisition systems and circuits, nuclear medicine imaging and tomography, and nuclear radiation detectors. Consideration is given to high-energy physics instrumentation, reactor systems and safeguards, health physics instrumentation, and nuclear power systems.

Communication: An efficient approach to compute state-specific nuclear gradients for a generic state-averaged multi-configuration self consistent field wavefunction.

PubMed

Granovsky, Alexander A

2015-12-21

We present a new, very efficient semi-numerical approach for the computation of state-specific nuclear gradients of a generic state-averaged multi-configuration self consistent field wavefunction. Our approach eliminates the costly coupled-perturbed multi-configuration Hartree-Fock step as well as the associated integral transformation stage. The details of the implementation within the Firefly quantum chemistry package are discussed and several sample applications are given. The new approach is routinely applicable to geometry optimization of molecular systems with 1000+ basis functions using a standalone multi-core workstation.

Communication: An efficient approach to compute state-specific nuclear gradients for a generic state-averaged multi-configuration self consistent field wavefunction

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

Granovsky, Alexander A., E-mail: alex.granovsky@gmail.com

We present a new, very efficient semi-numerical approach for the computation of state-specific nuclear gradients of a generic state-averaged multi-configuration self consistent field wavefunction. Our approach eliminates the costly coupled-perturbed multi-configuration Hartree-Fock step as well as the associated integral transformation stage. The details of the implementation within the Firefly quantum chemistry package are discussed and several sample applications are given. The new approach is routinely applicable to geometry optimization of molecular systems with 1000+ basis functions using a standalone multi-core workstation.

Nuclear Reactor Physics

NASA Astrophysics Data System (ADS)

Stacey, Weston M.

2001-02-01

An authoritative textbook and up-to-date professional's guide to basic and advanced principles and practices Nuclear reactors now account for a significant portion of the electrical power generated worldwide. At the same time, the past few decades have seen an ever-increasing number of industrial, medical, military, and research applications for nuclear reactors. Nuclear reactor physics is the core discipline of nuclear engineering, and as the first comprehensive textbook and reference on basic and advanced nuclear reactor physics to appear in a quarter century, this book fills a large gap in the professional literature. Nuclear Reactor Physics is a textbook for students new to the subject, for others who need a basic understanding of how nuclear reactors work, as well as for those who are, or wish to become, specialists in nuclear reactor physics and reactor physics computations. It is also a valuable resource for engineers responsible for the operation of nuclear reactors. Dr. Weston Stacey begins with clear presentations of the basic physical principles, nuclear data, and computational methodology needed to understand both the static and dynamic behaviors of nuclear reactors. This is followed by in-depth discussions of advanced concepts, including extensive treatment of neutron transport computational methods. As an aid to comprehension and quick mastery of computational skills, he provides numerous examples illustrating step-by-step procedures for performing the calculations described and chapter-end problems. Nuclear Reactor Physics is a useful textbook and working reference. It is an excellent self-teaching guide for research scientists, engineers, and technicians involved in industrial, research, and military applications of nuclear reactors, as well as government regulators who wish to increase their understanding of nuclear reactors.

Studies of the QCD Phase Diagram with Heavy-Ion Collisions at J-PARC

NASA Astrophysics Data System (ADS)

Sako, Hiroyuki

To clarify phase structures in the QCD phase diagram is an ultimate goal of heavy-ion collision experiments. Studies of internal structures of neutron stars are also one of the most important topics of nuclear physics since the discovery of neutron stars with two-solar mass. For these physics goals, J-PARC heavy-ion project (J-PARC-HI) has been proposed, where extremely dense matter with 5-10 times the normal nuclear density will be created. Heavy-ion beams up to Uranium will be accelerated to 1-19 AGeV/c, with the designed world's highest beam rate of 1011 Hz. The acceleration of such high-rate beams can be realized by a new heavy-ion linac and a new booster ring, in addition to the existing 3-GeV and 50-GeV proton synchrotrons. To study the above physics goals, following physics observables will be measured in extremely high statistics expected in J-PARC-HI. To search for the critical point, high-order event-by-event fluctuations of conserved charges such as a net-baryon number, an electric charge number, and a strangeness number will be measured. To study the chiral symmetry restoration, dilepton spectra from light vector meson decays will be measured. Also, collective flows, particle correlations will be measured to study the equation of state and hyperon-hyperon and hyperon-nucleon interactions related to neutron stars. Strange quark matter (strangelet) and multi-strangeness hypernuclei will be searched for which may be related directly to the matter constituting the neutron star core. In this work, the physics goals, the experimental design, and expected physics results of J-PARC-HI will be discussed.

Constraining nuclear data via cosmological observations: Neutrino energy transport and big bang nucleosynthesis

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

Paris, Mark W.; Fuller, George M.; Grohs, Evan Bradley

Here, we introduce a new computational capability that moves toward a self-consistent calculation of neutrino transport and nuclear reactions for big bang nucleosynthesis (BBN). Such a self-consistent approach is needed to be able to extract detailed information about nuclear reactions and physics beyond the standard model from precision cosmological observations of primordial nuclides and the cosmic microwave background radiation. We also calculate the evolution of the early universe through the epochs of weak decoupling, weak freeze-out and big bang nucleosynthesis (BBN) by simultaneously coupling a full strong, electromagnetic, and weak nuclear reaction network with a multi-energy group Boltzmann neutrino energymore » transport scheme. The modular structure of our approach allows the dissection of the relative contributions of each process responsible for evolving the dynamics of the early universe. Such an approach allows a detailed account of the evolution of the active neutrino energy distribution functions alongside and self-consistently with the nuclear reactions and entropy/heat generation and flow between the neutrino and photon/electron/positron/baryon plasma components. Our calculations reveal nonlinear feedback in the time evolution of neutrino distribution functions and plasma thermodynamic conditions. We discuss the time development of neutrino spectral distortions and concomitant entropy production and extraction from the plasma. These effects result in changes in the computed values of the BBN deuterium and helium-4 yields that are on the order of a half-percent relative to a baseline standard BBN calculation with no neutrino transport. This is an order of magnitude larger effect than in previous estimates. For particular implementations of quantum corrections in plasma thermodynamics, our calculations show a 0.4% increase in deuterium and a 0.6% decrease in 4He over our baseline. The magnitude of these changes are on the order of uncertainties in the nuclear physics for the case of deuterium and are potentially significant for the error budget of helium in upcoming cosmological observations.« less

Constraining nuclear data via cosmological observations: Neutrino energy transport and big bang nucleosynthesis

NASA Astrophysics Data System (ADS)

Paris, Mark; Fuller, George; Grohs, Evan; Kishimoto, Chad; Vlasenko, Alexey

2017-09-01

We introduce a new computational capability that moves toward a self-consistent calculation of neutrino transport and nuclear reactions for big bang nucleosynthesis (BBN). Such a self-consistent approach is needed to be able to extract detailed information about nuclear reactions and physics beyond the standard model from precision cosmological observations of primordial nuclides and the cosmic microwave background radiation. We calculate the evolution of the early universe through the epochs of weak decoupling, weak freeze-out and big bang nucleosynthesis (BBN) by simultaneously coupling a full strong, electromagnetic, and weak nuclear reaction network with a multi-energy group Boltzmann neutrino energy transport scheme. The modular structure of our approach allows the dissection of the relative contributions of each process responsible for evolving the dynamics of the early universe. Such an approach allows a detailed account of the evolution of the active neutrino energy distribution functions alongside and self-consistently with the nuclear reactions and entropy/heat generation and 'ow between the neutrino and photon/electron/positron/baryon plasma components. Our calculations reveal nonlinear feedback in the time evolution of neutrino distribution functions and plasma thermodynamic conditions. We discuss the time development of neutrino spectral distortions and concomitant entropy production and extraction from the plasma. These e↑ects result in changes in the computed values of the BBN deuterium and helium-4 yields that are on the order of a half-percent relative to a baseline standard BBN calculation with no neutrino transport. This is an order of magnitude larger e↑ect than in previous estimates. For particular implementations of quantum corrections in plasma thermodynamics, our calculations show a 0.4% increase in deuterium and a 0.6% decrease in 4He over our baseline. The magnitude of these changes are on the order of uncertainties in the nuclear physics for the case of deuterium and are potentially signi↓cant for the error budget of helium in upcoming cosmological observations.

Constraining nuclear data via cosmological observations: Neutrino energy transport and big bang nucleosynthesis

DOE PAGES

Paris, Mark W.; Fuller, George M.; Grohs, Evan Bradley; ...

2017-09-13

Here, we introduce a new computational capability that moves toward a self-consistent calculation of neutrino transport and nuclear reactions for big bang nucleosynthesis (BBN). Such a self-consistent approach is needed to be able to extract detailed information about nuclear reactions and physics beyond the standard model from precision cosmological observations of primordial nuclides and the cosmic microwave background radiation. We also calculate the evolution of the early universe through the epochs of weak decoupling, weak freeze-out and big bang nucleosynthesis (BBN) by simultaneously coupling a full strong, electromagnetic, and weak nuclear reaction network with a multi-energy group Boltzmann neutrino energymore » transport scheme. The modular structure of our approach allows the dissection of the relative contributions of each process responsible for evolving the dynamics of the early universe. Such an approach allows a detailed account of the evolution of the active neutrino energy distribution functions alongside and self-consistently with the nuclear reactions and entropy/heat generation and flow between the neutrino and photon/electron/positron/baryon plasma components. Our calculations reveal nonlinear feedback in the time evolution of neutrino distribution functions and plasma thermodynamic conditions. We discuss the time development of neutrino spectral distortions and concomitant entropy production and extraction from the plasma. These effects result in changes in the computed values of the BBN deuterium and helium-4 yields that are on the order of a half-percent relative to a baseline standard BBN calculation with no neutrino transport. This is an order of magnitude larger effect than in previous estimates. For particular implementations of quantum corrections in plasma thermodynamics, our calculations show a 0.4% increase in deuterium and a 0.6% decrease in 4He over our baseline. The magnitude of these changes are on the order of uncertainties in the nuclear physics for the case of deuterium and are potentially significant for the error budget of helium in upcoming cosmological observations.« less

Purification, characterization, and sequencing of novel antimicrobial peptides, Tu-AMP 1 and Tu-AMP 2, from bulbs of tulip (Tulipa gesneriana L.).

PubMed

Fujimura, Masatoshi; Ideguchi, Mineo; Minami, Yuji; Watanabe, Keiichi; Tadera, Kenjiro

2004-03-01

Novel antimicrobial peptides (AMP), designated Tu-AMP 1 and Tu-AMP 2, were purified from the bulbs of tulip (Tulipa gesneriana L.) by chitin affinity chromatography and reverse-phase high-performance liquid chromatography (HPLC). They bind to chitin in a reversible way. They were basic peptides having isoelectric points of over 12. Tu-AMP 1 and Tu-AMP 2 had molecular masses of 4,988 Da and 5,006 Da on MALDI-TOF MS analysis, and their extinction coefficients of 1% aqueous solutions at 280 nm were 3.3 and 3.4, respectively. Half of all amino acid residues of Tu-AMP 1 and Tu-AMP 2 were occupied by cysteine, arginine, lysine, and proline. The concentrations of peptides required for 50% inhibition (IC(50)) of the growth of plant pathogenic bacteria and fungi were 2 to 20 microg/ml. The structural characteristics of Tu-AMP 1 and Tu-AMP 2 indicated that they were novel thionin-like antimicrobial peptides, though Tu-AMP 2 was a heterodimer composes of two short peptides joined with disulfide bonds.

Studying Si/SiGe disordered alloys within effective mass theory

NASA Astrophysics Data System (ADS)

Gamble, John; Montaño, Inès; Carroll, Malcolm S.; Muller, Richard P.

Si/SiGe is an attractive material system for electrostatically-defined quantum dot qubits due to its high-quality crystalline quantum well interface. Modeling the properties of single-electron quantum dots in this system is complicated by the presence of alloy disorder, which typically requires atomistic techniques in order to treat properly. Here, we use the NEMO-3D empirical tight binding code to calibrate a multi-valley effective mass theory (MVEMT) to properly handle alloy disorder. The resulting MVEMT simulations give good insight into the essential physics of alloy disorder, while being extremely computationally efficient and well-suited to determining statistical properties. Sandia is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the US Department of Energy's National Nuclear Security Administration under Contract No. DE-AC04-94AL85000.

NuSTAR observations of GRB 130427A establish a single component synchrotron afterglow origin for the late optical to multi-GEV emission

DOE PAGES

Kouveliotou, Chryssa; Granot, J.; Racusin, J. L.; ...

2013-11-21

Here, GRB 130427A occurred in a relatively nearby galaxy; its prompt emission had the largest GRB fluence ever recorded. The afterglow of GRB 130427A was bright enough for the Nuclear Spectroscopic Telescope ARray ( NuSTAR) to observe it in the 3-79 keV energy range long after its prompt emission (~1.5 and 5 days). This range, where afterglow observations were previously not possible, bridges an important spectral gap. Combined with Swift, Fermi, and ground-based optical data, NuSTAR observations unambiguously establish a single afterglow spectral component from optical to multi-GeV energies a day after the event, which is almost certainly synchrotron radiation.more » Such an origin of the late-time Fermi/Large Area Telescope >10 GeV photons requires revisions in our understanding of collisionless relativistic shock physics.« less

Transport properties of LiF under strong compression: modeling using advanced electronic structure methods and classical molecular dynamics

NASA Astrophysics Data System (ADS)

Mattsson, Thomas R.; Jones, Reese; Ward, Donald; Spataru, Catalin; Shulenburger, Luke; Benedict, Lorin X.

2015-06-01

Window materials are ubiquitous in shock physics and with high energy density drivers capable of reaching multi-Mbar pressures the use of LiF is increasing. Velocimetry and temperature measurements of a sample through a window are both influenced by the assumed index of refraction and thermal conductivity, respectively. We report on calculations of index of refraction using the many-body theory GW and thermal ionic conductivity using linear response theory and model potentials. The results are expected to increase the accuracy of a broad range of high-pressure shock- and ramp compression experiments. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Company, for the U.S. Department of Energy's National Nuclear Security Administration under Contract DE-AC04-94AL85000.

The Multi-dimensional Character of Core-collapse Supernovae

DOE PAGES

Hix, W. R.; Lentz, E. J.; Bruenn, S. W.; ...

2016-03-01

Core-collapse supernovae, the culmination of massive stellar evolution, are spectacular astronomical events and the principle actors in the story of our elemental origins. Our understanding of these events, while still incomplete, centers around a neutrino-driven central engine that is highly hydrodynamically unstable. Increasingly sophisticated simulations reveal a shock that stalls for hundreds of milliseconds before reviving. Though brought back to life by neutrino heating, the development of the supernova explosion is inextricably linked to multi-dimensional fluid flows. In this paper, the outcomes of three-dimensional simulations that include sophisticated nuclear physics and spectral neutrino transport are juxtaposed to learn about themore » nature of the three-dimensional fluid flow that shapes the explosion. Comparison is also made between the results of simulations in spherical symmetry from several groups, to give ourselves confidence in the understanding derived from this juxtaposition.« less

Nuclear winter - Physics and physical mechanisms

NASA Technical Reports Server (NTRS)

Turco, R. P.; Toon, O. B.; Pollack, J. B.; Ackerman, T. P.; Sagan, C.

1991-01-01

The basic physics of the environmental perturbations caused by multiple nuclear detonations is explored, summarizing current knowledge of the possible physical, chemical, and biological impacts of nuclear war. Emphasis is given to the impact of the bomb-generated smoke (soot) particles. General classes of models that have been used to simulate nuclear winter are examined, using specific models as examples.

The contribution of Medical Physics to Nuclear Medicine: looking back - a physicist's perspective.

PubMed

Hutton, Brian F

2014-12-01

This paper is the first in a series of invited perspectives by four pioneers of Nuclear Medicine imaging and physics. A medical physicist and a Nuclear Medicine clinical specialist each take a backward look and a forward look at the contributions of Medical Physics to Nuclear Medicine. Contributions of Medical Physics are presented from the early discovery of radioactivity, development of first imaging devices, computers and emission tomography to recent development of hybrid imaging. There is evidence of significant contribution of Medical Physics throughout the development of Nuclear Medicine.

NUCLEAR CHEMISTRY ANNUAL REPORT 1970

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

Authors, Various

Papers are presented for the following topics: (1) Nuclear Structure and Nuclear Properties - (a) Nuclear Spectroscopy and Radioactivity; (b) Nuclear Reactions and Scattering; (c) Nuclear Theory; and (d) Fission. (2) Chemical and Atomic Physics - (a) Atomic and Molecular Spectroscopy; and (b) Hyperfine Interactions. (3) Physical, Inorganic, and Analytical Chemistry - (a) X-Ray Crystallography; (b) Physical and Inorganic Chemistry; (c) Radiation Chemistry; and (d) Chemical Engineering. (4) Instrumentation and Systems Development.

Superstructure based on β-CD self-assembly induced by a small guest molecule†

PubMed Central

De Sousa, Frederico B.; Lima, Ana C.; Denadai, Ângelo M. L.; Anconi, Cleber P. A.; De Almeida, Wagner B.; Novato, Willian T. G.; Dos Santos, Hélio F.; Drum, Chester L.; Langer, Robert

2014-01-01

The size, shape and surface chemistry of nanoparticles play an important role in cellular interaction. Thus, the main objective of the present study was the determination of the β-cyclodextrin (β-CD) self-assembly thermodynamic parameters and its structure, aiming to use these assemblies as a possible controlled drug release system. Light scattering measurements led us to obtain the β-CD’s critical aggregation concentration (cac) values, and consequently the thermodynamic parameters of the β-CD spontaneous self-assembly in aqueous solution: ΔaggGo = − 16.31 kJ mol−1, ΔaggHo = − 26.48 kJ mol−1 and TΔaggSo = − 10.53 kJ mol−1 at 298.15 K. Size distribution of the self-assembled nanoparticles below and above cac was 1.5 nm and 60–120 nm, respectively. The number of β-CD molecules per cluster and the second virial coefficient were identified through Debye’s plot and molecular dynamic simulations proposed the three-fold assembly for this system below cac. Ampicillin (AMP) was used as a drug model in order to investigate the key role of the guest molecule in the self-assembly process and the β-CD:AMP supramolecular system was studied in solution, aiming to determine the structure of the supramolecular aggregate. Results obtained in solution indicated that the β-CD’s cac was not affected by adding AMP. Moreover, different complex stoichiometries were identified by nuclear magnetic resonance and isothermal titration calorimetry experiments. PMID:22234498

Chlorogenic acid ameliorates endotoxin-induced liver injury by promoting mitochondrial oxidative phosphorylation

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

Zhou, Yan; College of Food Safety, Guizhou Medical University, Guiyang 550025; Ruan, Zheng, E-mail: ruanzheng@ncu.edu.cn

Acute or chronic hepatic injury is a common pathology worldwide. Mitochondrial dysfunction and the depletion of adenosine triphosphate (ATP) play important roles in liver injury. Chlorogenic acids (CGA) are some of the most abundant phenolic acids in human diet. This study was designed to test the hypothesis that CGA may protect against chronic lipopolysaccharide (LPS)-induced liver injury by modulating mitochondrial energy generation. CGA decreased the activities of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. The contents of ATP and adenosine monophosphate (AMP), as well as the ratio of AMP/ATP, were increased after CGA supplementation. The activities of enzymes thatmore » are involved in glycolysis were reduced, while those of enzymes involved in oxidative phosphorylation were increased. Moreover, phosphorylated AMP-activated protein kinase (AMPK), and mRNA levels of AMPK-α, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial DNA transcription factor A were increased after CGA supplementation. Collectively, these findings suggest that the hepatoprotective effect of CGA might be associated with enhanced ATP production, the stimulation of mitochondrial oxidative phosphorylation and the inhibition of glycolysis. - Highlights: • Dietary supplementation with chlorogenic acid (CGA) improved endotoxin-induced liver injury. • Chlorogenic acid enhances ATP increase and shifts energy metabolism, which is correlated with up-regulation AMPK and PGC-1α. • The possible mechanism of CGA on mitochondrial biogenesis was correlated with up-regulation AMPK and PGC-1α.« less

The orphan nuclear receptor Nur77 regulates decidual prolactin expression in human endometrial stromal cells

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

Jiang, Yue; Hu, Yali; Zhao, Jing

2011-01-14

Research highlights: {yields} Decidually produced PRL plays a key role during pregnancy. {yields} Overexpression of Nur77 increased PRL mRNA expression and enhanced decidual PRL promoter activity. {yields} Knockdown of Nur77 decreased decidual PRL secretion induced by 8-Br-cAMP and MPA. {yields} Nur77 is a novel transcription factor that plays an active role in decidual prolactin expression. -- Abstract: Prolactin (PRL) is synthesized and released by several extrapituitary tissues, including decidualized stromal cells. Despite the important role of decidual PRL during pregnancy, little is understood about the factors involved in the proper regulation of decidual PRL expression. Here we present evidence thatmore » the transcription factor Nur77 plays an active role in decidual prolactin expression in human endometrial stromal cells (hESCs). Nur77 mRNA expression in hESCs was significantly increased after decidualization stimulated by 8-Br-cAMP and medroxyprogesterone acetate (MPA). Adenovirus-mediated overexpression of Nur77 in hESCs markedly increased PRL mRNA expression and enhanced decidual PRL promoter (dPRL/-332Luc) activity in a concentration-dependent manner. Furthermore, knockdown of Nur77 in hESCs significantly decreased decidual PRL promoter activation and substantially attenuated PRL mRNA expression and PRL secretion (P < 0.01) induced by 8-Br-cAMP and MPA. These results demonstrate that Nur77 is a novel transcription factor that contributes significantly to the regulation of prolactin gene expression in human endometrial stromal cells.« less

Role of 2',3'-cyclic nucleotide 3'-phosphodiesterase in the renal 2',3'-cAMP-adenosine pathway.

PubMed

Jackson, Edwin K; Gillespie, Delbert G; Mi, Zaichuan; Cheng, Dongmei; Bansal, Rashmi; Janesko-Feldman, Keri; Kochanek, Patrick M

2014-07-01

Energy depletion increases the renal production of 2',3'-cAMP (a positional isomer of 3',5'-cAMP that opens mitochondrial permeability transition pores) and 2',3'-cAMP is converted to 2'-AMP and 3'-AMP, which in turn are metabolized to adenosine. Because the enzymes involved in this "2',3'-cAMP-adenosine pathway" are unknown, we examined whether 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) participates in the renal metabolism of 2',3'-cAMP. Western blotting and real-time PCR demonstrated expression of CNPase in rat glomerular mesangial, preglomerular vascular smooth muscle and endothelial, proximal tubular, thick ascending limb and collecting duct cells. Real-time PCR established the expression of CNPase in human glomerular mesangial, proximal tubular and vascular smooth muscle cells; and the level of expression of CNPase was greater than that for phosphodiesterase 4 (major enzyme for the metabolism of 3',5'-cAMP). Overexpression of CNPase in rat preglomerular vascular smooth muscle cells increased the metabolism of exogenous 2',3'-cAMP to 2'-AMP. Infusions of 2',3'-cAMP into isolated CNPase wild-type (+/+) kidneys increased renal venous 2'-AMP, and this response was diminished by 63% in CNPase knockout (-/-) kidneys, whereas the conversion of 3',5'-cAMP to 5'-AMP was similar in CNPase +/+ vs. -/- kidneys. In CNPase +/+ kidneys, energy depletion (metabolic poisons) increased kidney tissue levels of adenosine and its metabolites (inosine, hypoxanthine, xanthine, and uric acid) without accumulation of 2',3'-cAMP. In contrast, in CNPase -/- kidneys, energy depletion increased kidney tissue levels of 2',3'-cAMP and abolished the increase in adenosine and its metabolites. In conclusion, kidneys express CNPase, and renal CNPase mediates in part the renal 2',3'-cAMP-adenosine pathway. Copyright © 2014 the American Physiological Society.

Extragalactic circuits, transmission lines, and CR particle acceleration

NASA Astrophysics Data System (ADS)

Kronberg, Philipp P.; Lovelace, Richard V. E.

2015-08-01

A non-negligible fraction of a Supermassive Black Hole's (SMBH) rest mass energy gets transported into extragalactic space by a remarkable process in jets which are incompletely understood. What are the physical processes which transport this energy? It is likely that the energy flows electromagnetically, rather than via a particle beam flux. The deduced electromagnetic fields may produce particles of energy as high as ˜ 1020 eV. The energetics of SMBH accretion disk models and the electromagnetic energy transfer imply that a SMBH should generate a 1018 - 1019 Ampères current close to the black hole and its accretion disk. We describe the so far best observation-based estimate of the magnitude of the current flow along the axis of the jet extending from the nucleus of the active galaxy in 3C303. The current is measured to be I ˜ 1018 Ampères at ˜ 40 kpc away from the AGN. This indicates that organised current flow remains intact over multi-kpc distances. The electric current I transports electromagnetic power into free space, P = I2Z, where Z ˜ 30 Ohms is related to the impedance of free space, and this points to the existence of cosmic electric circuit. The associated electric potential drop, V = IZ, is of the order of that required to generate Ultra High Energy Cosmic Rays (UHECR). We also explore further implications, including disruption/deflection of the power flow and also why such measurements, exemplified by those on 3C303, are currently very difficult to make and to unambiguously interpret. This naturally leads to the topic of how such measurements can be extended and improved in the future. We describe the analogy of electromagnetically dominated jets with transmission lines. High powered jets in vacuo can be understood by approximate analogy with a waveguide. The importance of inductance, impedance, and other laboratory electrical concepts are discussed in this context.

Ion kinetic dynamics in strongly-shocked plasmas relevant to ICF

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

Rinderknecht, H. G.; Amendt, P. A.; Rosenberg, M. J.

Implosions of thin-shell capsules produce strongly-shocked (M > 10), low-density (ρ ~1 mg/cc -1), high-temperature (T i ~keV) plasmas, comparable to those produced in the strongly-shocked DT-vapor in inertial confinement fusion (ICF) experiments. A series of thin-glass targets filled with mixtures of deuterium and Helium-3 gas ranging from 7% to 100% deuterium was imploded to investigate the impact of multi-species ion kinetic mechanisms in ICF-relevant plasmas over a wide range of Knudsen numbers (N K ≡ λ ii/R). Anomalous trends in nuclear yields and burn-averaged ion temperatures in implosions with N K > 0.5, which have been interpreted as signaturesmore » of ion species separation and ion thermal decoupling, are found not to be consistent with single-species ion kinetic effects alone. Experimentally inferred Knudsen numbers predict an opposite yield trend to those observed, confirming the dominance of multi-species physics in these experiments. In contrast, implosions with N K ~ 0.01 follow the expected yield trend, suggesting single-species kinetic effects are dominant. In conclusion, the impact of the observed kinetic physics mechanisms on the formation of the hotspot in ICF experiments is discussed.« less

Ion kinetic dynamics in strongly-shocked plasmas relevant to ICF

DOE PAGES

Rinderknecht, H. G.; Amendt, P. A.; Rosenberg, M. J.; ...

2017-04-20

Implosions of thin-shell capsules produce strongly-shocked (M > 10), low-density (ρ ~1 mg/cc -1), high-temperature (T i ~keV) plasmas, comparable to those produced in the strongly-shocked DT-vapor in inertial confinement fusion (ICF) experiments. A series of thin-glass targets filled with mixtures of deuterium and Helium-3 gas ranging from 7% to 100% deuterium was imploded to investigate the impact of multi-species ion kinetic mechanisms in ICF-relevant plasmas over a wide range of Knudsen numbers (N K ≡ λ ii/R). Anomalous trends in nuclear yields and burn-averaged ion temperatures in implosions with N K > 0.5, which have been interpreted as signaturesmore » of ion species separation and ion thermal decoupling, are found not to be consistent with single-species ion kinetic effects alone. Experimentally inferred Knudsen numbers predict an opposite yield trend to those observed, confirming the dominance of multi-species physics in these experiments. In contrast, implosions with N K ~ 0.01 follow the expected yield trend, suggesting single-species kinetic effects are dominant. In conclusion, the impact of the observed kinetic physics mechanisms on the formation of the hotspot in ICF experiments is discussed.« less

Pulse Shape Discrimination in the MAJORANA DEMONSTRATOR

NASA Astrophysics Data System (ADS)

Haufe, Christopher; Majorana Collaboration

2017-09-01

The MAJORANA DEMONSTRATOR is an experiment constructed to search for neutrinoless double-beta decays in germanium-76 and to demonstrate the feasibility to deploy a large-scale experiment in a phased and modular fashion. It consists of two modular arrays of natural and 76Ge-enriched germanium p-type point contact detectors totaling 44.1 kg, located at the 4850' level of the Sanford Underground Research Facility in Lead, South Dakota, USA. A large effort is underway to analyze the data currently being taken by the DEMONSTRATOR. Key components of this effort are analysis tools that allow for pulse shape discrimination-techniques that significantly reduce background levels in the neutrinoless double-beta decay region of interest. These tools are able to identify and reject multi-site events from Compton scattering as well as events from alpha particle interactions. This work serves as an overview for these analysis tools and highlights the unique advantages that the HPGe p-type point contact detector provides to pulse shape discrimination. This material is supported by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics, the Particle Astrophysics and Nuclear Physics Programs of the National Science Foundation, and the Sanford Underground Research Facility.

Network inference reveals novel connections in pathways regulating growth and defense in the yeast salt response.

PubMed

MacGilvray, Matthew E; Shishkova, Evgenia; Chasman, Deborah; Place, Michael; Gitter, Anthony; Coon, Joshua J; Gasch, Audrey P

2018-05-01

Cells respond to stressful conditions by coordinating a complex, multi-faceted response that spans many levels of physiology. Much of the response is coordinated by changes in protein phosphorylation. Although the regulators of transcriptome changes during stress are well characterized in Saccharomyces cerevisiae, the upstream regulatory network controlling protein phosphorylation is less well dissected. Here, we developed a computational approach to infer the signaling network that regulates phosphorylation changes in response to salt stress. We developed an approach to link predicted regulators to groups of likely co-regulated phospho-peptides responding to stress, thereby creating new edges in a background protein interaction network. We then use integer linear programming (ILP) to integrate wild type and mutant phospho-proteomic data and predict the network controlling stress-activated phospho-proteomic changes. The network we inferred predicted new regulatory connections between stress-activated and growth-regulating pathways and suggested mechanisms coordinating metabolism, cell-cycle progression, and growth during stress. We confirmed several network predictions with co-immunoprecipitations coupled with mass-spectrometry protein identification and mutant phospho-proteomic analysis. Results show that the cAMP-phosphodiesterase Pde2 physically interacts with many stress-regulated transcription factors targeted by PKA, and that reduced phosphorylation of those factors during stress requires the Rck2 kinase that we show physically interacts with Pde2. Together, our work shows how a high-quality computational network model can facilitate discovery of new pathway interactions during osmotic stress.

Cancer-induced cardiac cachexia: Pathogenesis and impact of physical activity (Review).

PubMed

Belloum, Yassine; Rannou-Bekono, Françoise; Favier, François B

2017-05-01

Cachexia is a wasting syndrome observed in many patients suffering from several chronic diseases including cancer. In addition to the progressive loss of skeletal muscle mass, cancer cachexia results in cardiac function impairment. During the severe stage of the disease, patients as well as animals bearing cancer cells display cardiac atrophy. Cardiac energy metabolism is also impeded with disruption of mitochondrial homeostasis and reduced oxidative capacity, although the available data remain equivocal. The release of inflammatory cytokines by tumor is a key mechanism in the initiation of heart failure. Oxidative stress, which results from the combination of chemotherapy, inadequate antioxidant consumption and chronic inflammation, will further foster heart failure. Protein catabolism is due to the concomitant activation of proteolytic systems and inhibition of protein synthesis, both processes being triggered by the deactivation of the Akt/mammalian target of rapamycin pathway. The reduction in oxidative capacity involves AMP-activated protein kinase and peroxisome proliferator-activated receptor gamma coactivator 1α dysregulation. The nuclear factor-κB transcription factor plays a prominent role in the coordination of these alterations. Physical exercise appears as an interesting non-pharmaceutical way to counteract cancer cachexia-induced-heart failure. Indeed, aerobic training has anti-inflammatory effects, increases anti-oxidant defenses, prevents atrophy and promotes oxidative metabolism. The present review points out the importance of better understanding the concurrent structural and metabolic changes within the myocardium during cancer and the protective effects of exercise against cardiac cachexia.

Validation of a multi-layer Green's function code for ion beam transport

NASA Astrophysics Data System (ADS)

Walker, Steven; Tweed, John; Tripathi, Ram; Badavi, Francis F.; Miller, Jack; Zeitlin, Cary; Heilbronn, Lawrence

To meet the challenge of future deep space programs, an accurate and efficient engineering code for analyzing the shielding requirements against high-energy galactic heavy radiations is needed. In consequence, a new version of the HZETRN code capable of simulating high charge and energy (HZE) ions with either laboratory or space boundary conditions is currently under development. The new code, GRNTRN, is based on a Green's function approach to the solution of Boltzmann's transport equation and like its predecessor is deterministic in nature. The computational model consists of the lowest order asymptotic approximation followed by a Neumann series expansion with non-perturbative corrections. The physical description includes energy loss with straggling, nuclear attenuation, nuclear fragmentation with energy dispersion and down shift. Code validation in the laboratory environment is addressed by showing that GRNTRN accurately predicts energy loss spectra as measured by solid-state detectors in ion beam experiments with multi-layer targets. In order to validate the code with space boundary conditions, measured particle fluences are propagated through several thicknesses of shielding using both GRNTRN and the current version of HZETRN. The excellent agreement obtained indicates that GRNTRN accurately models the propagation of HZE ions in the space environment as well as in laboratory settings and also provides verification of the HZETRN propagator.

Dietary α-lactalbumin induced fatty liver by enhancing nuclear liver X receptor αβ/sterol regulatory element-binding protein-1c/PPARγ expression and minimising PPARα/carnitine palmitoyltransferase-1 expression and AMP-activated protein kinase α phosphorylation associated with atherogenic dyslipidaemia, insulin resistance and oxidative stress in Balb/c mice.

PubMed

López-Oliva, María Elvira; Garcimartin, Alba; Muñoz-Martínez, Emilia

2017-12-01

The effect and the role played by dietary α-lactalbumin (α-LAC) on hepatic fat metabolism are yet to be fully elucidated. We reported previously that α-LAC intake induced atherogenic dyslipidaemia in Balb/c mice. The aim of the present study was to investigate if this atherogenic effect could be due to a possible α-LAC-induced hepatic steatosis. We examine the ability of dietary α-LAC to induce liver steatosis, identifying the molecular mechanisms underlying hepatic lipid metabolism in association with the lipid profile, peripheral insulin resistance (IR) and changes in the hepatic oxidative environment. Male Balb/c mice (n 6) were fed with diets containing either chow or 14 % α-LAC for 4 weeks. The α-LAC-fed mice developed abdominal adiposity and IR. Moderate liver steatosis with increased TAG and NEFA contents was correlated with atherogenic dyslipidaemia. There was increased nuclear expression of liver X receptor αβ (LXRαβ), sterol regulatory element-binding protein-1c (SREBP-1c) and PPARγ transcription factors and of the cytosolic enzymes acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase involved in the hepatic de novo lipogenesis. The opposite was found for the nuclear receptor PPARα and the mitochondrial enzyme carnitine palmitoyltransferase-1 (CPT-1), leading to reduced fatty acid β-oxidation (FAO). These changes were associated with a significant decrease in both p-Thr172-AMP-activated protein kinase α (AMPKα) (inactivation) and p-Ser79-ACC1 (activation) and with a more oxidative liver environment increasing lipid peroxidation and protein oxidation and reducing GSH:GSSG ratio in the α-LAC-fed mice. In conclusion, 4 weeks of 14 % α-LAC feeding induced liver steatosis associated with atherogenic dyslipidaemia, IR and oxidative stress by enhancing nuclear LXRαβ/SREBP-1c/PPARγ expression and diminishing PPARα/CPT-1 expression and AMPKα phosphorylation shifting the hepatic FAO toward fatty acid synthesis in Balb/c mice.

Novel Sorbent Development and Evaluation for the Capture of Krypton and Xenon from Nuclear Fuel Reprocessing Off-Gas Streams

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

Troy G. Garn; Mitchell R. Greenhalgh; Jack D. Law

2013-10-01

The release of volatile radionuclides generated during Used Nuclear Fuel reprocessing in the US will most certainly need to be controlled to meet US regulatory emission limits. A US DOE sponsored Off-Gas Sigma Team has been tasked with a multi-lab collaborative research and development effort to investigate and evaluate emissions and immobilization control technologies for the volatile radioactive species generated from commercial Used Nuclear Fuel (UNF) Reprocessing. Physical Adsorption technology is a simpler and potential economical alternative to cryogenic distillation processes that can be used for the capture of krypton and xenon and has resulted in a novel composite sorbentmore » development procedure using synthesized mordenite as the active material. Utilizing the sorbent development procedure, INL sigma team members have developed two composite sorbents that have been evaluated for krypton and xenon capacities at ambient and 191 K temperature using numerous test gas compositions. Adsorption isotherms have been generated to predict equilibration and maximum capacities enabling modeling to support process equipment scale-up.« less

Novel Sorbent Development and Evaluation for the Capture of Krypton and Xenon from Nuclear Fuel Reprocessing Off-Gas Streams

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

Troy G. Garn; Mitchell R. Greenhalgh; Jack D. Law

2013-09-01

The release of volatile radionuclides generated during Used Nuclear Fuel reprocessing in the US will most certainly need to be controlled to meet US regulatory emission limits. A US DOE sponsored Off-Gas Sigma Team has been tasked with a multi-lab collaborative research and development effort to investigate and evaluate emissions and immobilization control technologies for the volatile radioactive species generated from commercial Used Nuclear Fuel (UNF) Reprocessing. Physical Adsorption technology is a simpler and potential economical alternative to cryogenic distillation processes that can be used for the capture of krypton and xenon and has resulted in a novel composite sorbentmore » development procedure using synthesized mordenite as the active material. Utilizing the sorbent development procedure, INL sigma team members have developed two composite sorbents that have been evaluated for krypton and xenon capacities at ambient and 191 K temperature using numerous test gas compositions. Adsorption isotherms have been generated to predict equilibration and maximum capacities enabling modeling to support process equipment scale-up.« less

New insight into the binding modes of TNP-AMP to human liver fructose-1,6-bisphosphatase

NASA Astrophysics Data System (ADS)

Han, Xinya; Huang, Yunyuan; Zhang, Rui; Xiao, San; Zhu, Shuaihuan; Qin, Nian; Hong, Zongqin; Wei, Lin; Feng, Jiangtao; Ren, Yanliang; Feng, Lingling; Wan, Jian

2016-08-01

Human liver fructose-1,6-bisphosphatase (FBPase) contains two binding sites, a substrate fructose-1,6-bisphosphate (FBP) active site and an adenosine monophosphate (AMP) allosteric site. The FBP active site works by stabilizing the FBPase, and the allosteric site impairs the activity of FBPase through its binding of a nonsubstrate molecule. The fluorescent AMP analogue, 2‧,3‧-O-(2,4,6-trinitrophenyl)adenosine 5‧-monophosphate (TNP-AMP) has been used as a fluorescent probe as it is able to competitively inhibit AMP binding to the AMP allosteric site and, therefore, could be used for exploring the binding modes of inhibitors targeted on the allosteric site. In this study, we have re-examined the binding modes of TNP-AMP to FBPase. However, our present enzyme kinetic assays show that AMP and FBP both can reduce the fluorescence from the bound TNP-AMP through competition for FBPase, suggesting that TNP-AMP binds not only to the AMP allosteric site but also to the FBP active site. Mutagenesis assays of K274L (located in the FBP active site) show that the residue K274 is very important for TNP-AMP to bind to the active site of FBPase. The results further prove that TNP-AMP is able to bind individually to the both sites. Our present study provides a new insight into the binding mechanism of TNP-AMP to the FBPase. The TNP-AMP fluorescent probe can be used to exam the binding site of an inhibitor (the active site or the allosteric site) using FBPase saturated by AMP and FBP, respectively, or the K247L mutant FBPase.

New insight into the binding modes of TNP-AMP to human liver fructose-1,6-bisphosphatase.

PubMed

Han, Xinya; Huang, Yunyuan; Zhang, Rui; Xiao, San; Zhu, Shuaihuan; Qin, Nian; Hong, Zongqin; Wei, Lin; Feng, Jiangtao; Ren, Yanliang; Feng, Lingling; Wan, Jian

2016-08-05

Human liver fructose-1,6-bisphosphatase (FBPase) contains two binding sites, a substrate fructose-1,6-bisphosphate (FBP) active site and an adenosine monophosphate (AMP) allosteric site. The FBP active site works by stabilizing the FBPase, and the allosteric site impairs the activity of FBPase through its binding of a nonsubstrate molecule. The fluorescent AMP analogue, 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-monophosphate (TNP-AMP) has been used as a fluorescent probe as it is able to competitively inhibit AMP binding to the AMP allosteric site and, therefore, could be used for exploring the binding modes of inhibitors targeted on the allosteric site. In this study, we have re-examined the binding modes of TNP-AMP to FBPase. However, our present enzyme kinetic assays show that AMP and FBP both can reduce the fluorescence from the bound TNP-AMP through competition for FBPase, suggesting that TNP-AMP binds not only to the AMP allosteric site but also to the FBP active site. Mutagenesis assays of K274L (located in the FBP active site) show that the residue K274 is very important for TNP-AMP to bind to the active site of FBPase. The results further prove that TNP-AMP is able to bind individually to the both sites. Our present study provides a new insight into the binding mechanism of TNP-AMP to the FBPase. The TNP-AMP fluorescent probe can be used to exam the binding site of an inhibitor (the active site or the allosteric site) using FBPase saturated by AMP and FBP, respectively, or the K247L mutant FBPase. Copyright © 2016 Elsevier B.V. All rights reserved.

Sensitivity of GBM cells to cAMP agonist-mediated apoptosis correlates with CD44 expression and agonist resistance with MAPK signaling.

PubMed

Daniel, Paul M; Filiz, Gulay; Mantamadiotis, Theo

2016-12-01

In some cell types, activation of the second messenger cAMP leads to increased expression of proapoptotic Bim and subsequent cell death. We demonstrate that suppression of the cAMP pathway is a common event across many cancers and that pharmacological activation of cAMP in glioblastoma (GBM) cells leads to enhanced BIM expression and apoptosis in specific GBM cell types. We identified the MAPK signaling axis as the determinant of cAMP agonist sensitivity in GBM cells, with high MAPK activity corresponding to cAMP resistance and low activity corresponding to sensitization to cAMP-induced apoptosis. Sensitive cells were efficiently killed by cAMP agonists alone, while targeting both the cAMP and MAPK pathways in resistant GBM cells resulted in efficient apoptosis. We also show that CD44 is differentially expressed in cAMP agonist-sensitive and -resistant cells. We thus propose that CD44 may be a useful biomarker for distinguishing tumors that may be sensitive to cAMP agonists alone or cAMP agonists in combination with other pathway inhibitors. This suggests that using existing chemotherapeutic compounds in combination with existing FDA-approved cAMP agonists may fast track trials toward improved therapies for difficult-to-treat cancers, such as GBM.

Evaluation of coupling approaches for thermomechanical simulations

DOE PAGES

Novascone, S. R.; Spencer, B. W.; Hales, J. D.; ...

2015-08-10

Many problems of interest, particularly in the nuclear engineering field, involve coupling between the thermal and mechanical response of an engineered system. The strength of the two-way feedback between the thermal and mechanical solution fields can vary significantly depending on the problem. Contact problems exhibit a particularly high degree of two-way feedback between those fields. This paper describes and demonstrates the application of a flexible simulation environment that permits the solution of coupled physics problems using either a tightly coupled approach or a loosely coupled approach. In the tight coupling approach, Newton iterations include the coupling effects between all physics,more » while in the loosely coupled approach, the individual physics models are solved independently, and fixed-point iterations are performed until the coupled system is converged. These approaches are applied to simple demonstration problems and to realistic nuclear engineering applications. The demonstration problems consist of single and multi-domain thermomechanics with and without thermal and mechanical contact. Simulations of a reactor pressure vessel under pressurized thermal shock conditions and a simulation of light water reactor fuel are also presented. Here, problems that include thermal and mechanical contact, such as the contact between the fuel and cladding in the fuel simulation, exhibit much stronger two-way feedback between the thermal and mechanical solutions, and as a result, are better solved using a tight coupling strategy.« less

Carbon Nanotube Interconnect

NASA Technical Reports Server (NTRS)

Li, Jun (Inventor); Meyyappan, Meyya (Inventor)

2006-01-01

Method and system for fabricating an electrical interconnect capable of supporting very high current densities ( 10(exp 6)-10(exp 10) Amps/sq cm), using an array of one or more carbon nanotubes (CNTs). The CNT array is grown in a selected spaced apart pattern, preferably with multi-wall CNTs, and a selected insulating material, such as SiOw, or SiuNv is deposited using CVD to encapsulate each CNT in the array. An exposed surface of the insulating material is planarized to provide one or more exposed electrical contacts for one or more CNTs.

Skeletal muscle expresses the extracellular cyclic AMP–adenosine pathway

PubMed Central

Chiavegatti, T; Costa, V L; Araújo, M S; Godinho, R O

2007-01-01

Background and purpose: cAMP is a key intracellular signalling molecule that regulates multiple processes of the vertebrate skeletal muscle. We have shown that cAMP can be actively pumped out from the skeletal muscle cell. Since in other tissues, cAMP efflux had been associated with extracellular generation of adenosine, in the present study we have assessed the fate of interstitial cAMP and the existence of an extracellular cAMP-adenosine signalling pathway in skeletal muscle. Experimental approach: cAMP efflux and/or its extracellular degradation were analysed by incubating rat cultured skeletal muscle with exogenous cAMP, forskolin or isoprenaline. cAMP and its metabolites were quantified by radioassay or HPLC, respectively. Key results: Incubation of cells with exogenous cAMP was followed by interstitial accumulation of 5′-AMP and adenosine, a phenomenon inhibited by selective inhibitors of ecto-phosphodiesterase (DPSPX) and ecto-nucleotidase (AMPCP). Activation of adenylyl cyclase (AC) in cultured cells with forskolin or isoprenaline increased cAMP efflux and extracellular generation of 5′-AMP and adenosine. Extracellular cAMP-adenosine pathway was also observed after direct and receptor-dependent stimulation of AC in rat extensor muscle ex vivo. These events were attenuated by probenecid, an inhibitor of ATP binding cassette family transporters. Conclusions and implications: Our results show the existence of an extracellular biochemical cascade that converts cAMP into adenosine. The functional relevance of this extracellular signalling system may involve a feedback modulation of cellular response initiated by several G protein-coupled receptor ligands, amplifying cAMP influence to a paracrine mode, through its metabolite, adenosine. PMID:18157164

Amp: A modular approach to machine learning in atomistic simulations

NASA Astrophysics Data System (ADS)

Khorshidi, Alireza; Peterson, Andrew A.

2016-10-01

Electronic structure calculations, such as those employing Kohn-Sham density functional theory or ab initio wavefunction theories, have allowed for atomistic-level understandings of a wide variety of phenomena and properties of matter at small scales. However, the computational cost of electronic structure methods drastically increases with length and time scales, which makes these methods difficult for long time-scale molecular dynamics simulations or large-sized systems. Machine-learning techniques can provide accurate potentials that can match the quality of electronic structure calculations, provided sufficient training data. These potentials can then be used to rapidly simulate large and long time-scale phenomena at similar quality to the parent electronic structure approach. Machine-learning potentials usually take a bias-free mathematical form and can be readily developed for a wide variety of systems. Electronic structure calculations have favorable properties-namely that they are noiseless and targeted training data can be produced on-demand-that make them particularly well-suited for machine learning. This paper discusses our modular approach to atomistic machine learning through the development of the open-source Atomistic Machine-learning Package (Amp), which allows for representations of both the total and atom-centered potential energy surface, in both periodic and non-periodic systems. Potentials developed through the atom-centered approach are simultaneously applicable for systems with various sizes. Interpolation can be enhanced by introducing custom descriptors of the local environment. We demonstrate this in the current work for Gaussian-type, bispectrum, and Zernike-type descriptors. Amp has an intuitive and modular structure with an interface through the python scripting language yet has parallelizable fortran components for demanding tasks; it is designed to integrate closely with the widely used Atomic Simulation Environment (ASE), which makes it compatible with a wide variety of commercial and open-source electronic structure codes. We finally demonstrate that the neural network model inside Amp can accurately interpolate electronic structure energies as well as forces of thousands of multi-species atomic systems.

Apulian crust: Top to bottom

NASA Astrophysics Data System (ADS)

Amato, Alessandro; Bianchi, Irene; Agostinetti, Nicola Piana

2014-12-01

We investigate the crustal seismic structure of the Adria plate using teleseismic receiver functions (RF) recorded at 12 broadband seismic stations in the Apulia region. Detailed models of the Apulian crust, e.g. the structure of the Apulian Multi-layer Platform (AMP), are crucial for assessing the presence of potential décollements at different depth levels that may play a role in the evolution of the Apenninic orogen. We reconstruct S-wave velocity profiles applying a trans-dimensional Monte Carlo method for the inversion of RF data. Using this method, the resolution at the different depth level is completely dictated by the data and we avoid introducing artifacts in the crustal structure. We focus our study on three different key-elements: the Moho depth, the lower crust S-velocity, and the fine-structure of the AMP. We find a well defined and relatively flat Moho discontinuity below the region at 28-32 km depth, possibly indicating that the original Moho is still preserved in the area. The lower crust appears as a generally low velocity layer (average Vs = 3.7 km/s in the 15-26 km depth interval), likely suggestive of a felsic composition, with no significant velocity discontinuities except for its upper and lower boundaries where we find layering. Finally, for the shallow structure, the comparison of RF results with deep well stratigraphic and sonic log data allowed us to constrain the structure of the AMP and the presence of underlying Permo-Triassic (P-T) sediments. We find that the AMP structure displays small-scale heterogeneities in the region, with a thickness of the carbonates layers varying between 4 and 12 km, and is underlain by a thin, discontinuous layer of P-T terrigenous sediments, that are lacking in some areas. This fact may be due to the roughness in the original topography of the continental margins or to heterogeneities in its shallow structure due to the rifting process.

Establishment of inducible cAMP early repressor transgenic fibroblasts in a porcine model of human type 1 diabetes mellitus.

PubMed

Jung, Eui-Man; Kim, Yu-Kyung; Lee, Geun-Shik; Hyun, Sang-Hwan; Hwang, Woo-Suk; Jeung, Eui-Bae

2012-07-01

Diabetes mellitus is a metabolic disease caused by impaired insulin secretion from the pancreatic β cells and increased insulin resistance in peripheral tissues. Recently, the overexpression of inducible cyclic AMP (cAMP) early repressor (ICER) Iγ in rodent pancreatic β cells was found to induce insulin deficiency and glucagon overproduction similar to that found in human diabetes mellitus. ICER Iγ with only a DNA binding domain interrupts the transcriptional regulation of the cAMP responsive element-binding protein (CREB) target genes. Based on this information, we hypothesized that the overexpression of ICER Iγ, the most powerful competitor to CREB, could be useful for generating a pig model of diabetes. First, we evaluated the promoter activities of the human insulin gene for the β cell-specific overexpression of ICER Iγ in the pig pancreas. The maximum promoter activity region [-1,431 nucleotides (nt) to +1 nt, +1 = the transcriptional start site] of the insulin gene presented an activity level 3-fold higher than a promoterless construct. Second, ICER Iγ overexpression controlled by this promoter region significantly blocked the glucose-mediated insulin transcription, such as that regulated by the viral promoter in the pancreatic β cell line, MIN6. This suggests that the human insulin promoter may facilitate the overexpression of ICER Iγ in porcine pancreatic β cells. In addition, the overexpression of ICER Iγ in porcine β cells may induce human-like type 1 diabetes mellitus in pigs. In the present study, we generated transgenic fibroblasts containing ICER Iγ cDNA controlled by the human insulin promoter, as well as two screening markers, the green fluorescence protein and the neomycin resistance gene. These fibroblasts may provide a source for somatic cell nuclear transfer to generate a pig model that mimics human diabetes mellitus.

Rp-cAMPS Prodrugs Reveal the cAMP Dependence of First-Phase Glucose-Stimulated Insulin Secretion

PubMed Central

Schwede, Frank; Chepurny, Oleg G.; Kaufholz, Melanie; Bertinetti, Daniela; Leech, Colin A.; Cabrera, Over; Zhu, Yingmin; Mei, Fang; Cheng, Xiaodong; Manning Fox, Jocelyn E.; MacDonald, Patrick E.; Genieser, Hans-G.; Herberg, Friedrich W.

2015-01-01

cAMP-elevating agents such as the incretin hormone glucagon-like peptide-1 potentiate glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. However, a debate has existed since the 1970s concerning whether or not cAMP signaling is essential for glucose alone to stimulate insulin secretion. Here, we report that the first-phase kinetic component of GSIS is cAMP-dependent, as revealed through the use of a novel highly membrane permeable para-acetoxybenzyl (pAB) ester prodrug that is a bioactivatable derivative of the cAMP antagonist adenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS). In dynamic perifusion assays of human or rat islets, a step-wise increase of glucose concentration leads to biphasic insulin secretion, and under these conditions, 8-bromoadenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer, 4-acetoxybenzyl ester (Rp-8-Br-cAMPS-pAB) inhibits first-phase GSIS by up to 80%. Surprisingly, second-phase GSIS is inhibited to a much smaller extent (≤20%). Using luciferase, fluorescence resonance energy transfer, and bioluminescence resonance energy transfer assays performed in living cells, we validate that Rp-8-Br-cAMPS-pAB does in fact block cAMP-dependent protein kinase activation. Novel effects of Rp-8-Br-cAMPS-pAB to block the activation of cAMP-regulated guanine nucleotide exchange factors (Epac1, Epac2) are also validated using genetically encoded Epac biosensors, and are independently confirmed in an in vitro Rap1 activation assay using Rp-cAMPS and Rp-8-Br-cAMPS. Thus, in addition to revealing the cAMP dependence of first-phase GSIS from human and rat islets, these findings establish a pAB-based chemistry for the synthesis of highly membrane permeable prodrug derivatives of Rp-cAMPS that act with micromolar or even nanomolar potency to inhibit cAMP signaling in living cells. PMID:26061564

Structural and Functional Characterization of Pseudomonas aeruginosa Global Regulator AmpR

PubMed Central

Caille, Olivier; Zincke, Diansy; Merighi, Massimo; Balasubramanian, Deepak; Kumari, Hansi; Kong, Kok-Fai; Silva-Herzog, Eugenia; Narasimhan, Giri; Schneper, Lisa; Lory, Stephen

2014-01-01

Pseudomonas aeruginosa is a dreaded pathogen in many clinical settings. Its inherent and acquired antibiotic resistance thwarts therapy. In particular, derepression of the AmpC β-lactamase is a common mechanism of β-lactam resistance among clinical isolates. The inducible expression of ampC is controlled by the global LysR-type transcriptional regulator (LTTR) AmpR. In the present study, we investigated the genetic and structural elements that are important for ampC induction. Specifically, the ampC (PampC) and ampR (PampR) promoters and the AmpR protein were characterized. The transcription start sites (TSSs) of the divergent transcripts were mapped using 5′ rapid amplification of cDNA ends-PCR (RACE-PCR), and strong σ54 and σ70 consensus sequences were identified at PampR and PampC, respectively. Sigma factor RpoN was found to negatively regulate ampR expression, possibly through promoter blocking. Deletion mapping revealed that the minimal PampC extends 98 bp upstream of the TSS. Gel shifts using membrane fractions showed that AmpR binds to PampC in vitro whereas in vivo binding was demonstrated using chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR). Additionally, site-directed mutagenesis of the AmpR helix-turn-helix (HTH) motif identified residues critical for binding and function (Ser38 and Lys42) and critical for function but not binding (His39). Amino acids Gly102 and Asp135, previously implicated in the repression state of AmpR in the enterobacteria, were also shown to play a structural role in P. aeruginosa AmpR. Alkaline phosphatase fusion and shaving experiments suggest that AmpR is likely to be membrane associated. Lastly, an in vivo cross-linking study shows that AmpR dimerizes. In conclusion, a potential membrane-associated AmpR dimer regulates ampC expression by direct binding. PMID:25182487

40 CFR 180.1149 - Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from...

Code of Federal Regulations, 2011 CFR

2011-07-01

... polyhedrosis virus of Anagrapha falcifera; exemption from the requirement of a tolerance. 180.1149 Section 180... Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from the... polyhedrosis virus of Anagrapha falcifera is exempted from the requirement of a tolerance in or on all raw...

40 CFR 180.1149 - Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from...

Code of Federal Regulations, 2014 CFR

2014-07-01

... polyhedrosis virus of Anagrapha falcifera; exemption from the requirement of a tolerance. 180.1149 Section 180... Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from the... polyhedrosis virus of Anagrapha falcifera is exempted from the requirement of a tolerance in or on all raw...

40 CFR 180.1149 - Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from...

Code of Federal Regulations, 2013 CFR

2013-07-01

... polyhedrosis virus of Anagrapha falcifera; exemption from the requirement of a tolerance. 180.1149 Section 180... Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from the... polyhedrosis virus of Anagrapha falcifera is exempted from the requirement of a tolerance in or on all raw...

40 CFR 180.1149 - Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from...

Code of Federal Regulations, 2012 CFR

2012-07-01

... polyhedrosis virus of Anagrapha falcifera; exemption from the requirement of a tolerance. 180.1149 Section 180... Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from the... polyhedrosis virus of Anagrapha falcifera is exempted from the requirement of a tolerance in or on all raw...

Comprehensive Glossary of Nuclear Science

NASA Astrophysics Data System (ADS)

Langlands, Tracy; Stone, Craig; Meyer, Richard

2001-10-01

We have developed a comprehensive glossary of terms covering the broad fields of nuclear and related areas of science. The glossary has been constructed with two sections. A primary section consists of over 6,000 terms covering the fields of nuclear and high energy physics, nuclear chemistry, radiochemistry, health physics, astrophysics, materials science, analytical science, environmental science, nuclear medicine, nuclear engineering, nuclear instrumentation, nuclear weapons, and nuclear safeguards. Approximately 1,500 terms of specific focus on military and nuclear weapons testing define the second section. The glossary is currently larger than many published glossaries and dictionaries covering the entire field of physics. Glossary terms have been defined using an extensive collection of current and historical publications. Historical texts extend back into the 1800's, the early days of atomic physics. The glossary has been developed both as a software application and as a hard copy document.

Effectiveness of a Mindfulness-Based Intervention in the Management of Musculoskeletal Pain in Nursing Workers.

PubMed

Lopes, Shirlene Aparecida; Vannucchi, Bruna Pesce; Demarzo, Marcelo; Cunha, Ângelo Geraldo José; Nunes, Maria do Patrocínio Tenório

2018-05-17

Chronic pain is a prevalent disorder in nursing workers worldwide. Several studies have proposed measures to mitigate this critical scenario. Mindfulness-based interventions (MBI) have been found to have promising results in the treatment of this disorder. To quantify the effectiveness of an adapted mindfulness program (AMP) in the management of musculoskeletal pain (MSP) in nursing technicians of a Brazilian university hospital. This study was a clinical, prospective, open, repeated measures trial, with data collection between January and July 2015. Brazilian university hospital. Participants/Subjects: Sixty-four female nursing technicians with a mean age of 47.01 years (standard deviation = 9.50) with chronic pain symptoms. Sixty-four female nursing technicians with a mean age of 47.01 years (standard deviation = 9.50) and MSP participated in this prospective study. Before the intervention (T0), scores of anxiety, depression, mindfulness, musculoskeletal complaints, pain catastrophizing, self-compassion, and perception of quality of life were quantified. These scores were reevaluated after 8 weeks (T1) and 12 weeks (T2) of weekly AMP sessions (60 minutes each). The variables were evaluated by analysis of variance for repeated measures, followed by the Bonferroni test. AMP reduced the scores of musculoskeletal symptoms, anxiety, depression, and pain catastrophizing (p < .001). A significant increase was identified in self-compassion scores and perception of quality of life in the physical, psychological, and overall assessment (p ≤ .04). Positive effects of AMP occurred at T1 and remained unchanged at T2. AMP contributed to a reduction in painful symptoms and improved the quality of life of nursing workers, with a lasting effect until the 20th week of follow-up, indicating utility as an effective strategy for the management of MSP in the group studied. Copyright © 2018 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

The contribution of medical physics to nuclear medicine: a physician's perspective.

PubMed

Ell, Peter J

2014-12-01

This paper is the second in a series of invited perspectives by four pioneers of nuclear medicine imaging and physics. A medical physicist and a nuclear medicine clinical specialist each take a backward look and a forward look at the contributions of physics to nuclear medicine. Here is a backward look from a nuclear medicine physician's perspective.

AMP-activated protein kinase and metabolic control

PubMed Central

Viollet, Benoit; Andreelli, Fabrizio

2011-01-01

AMP-activated protein kinase (AMPK), a phylogenetically conserved serine/threonine protein kinase, is a major regulator of cellular and whole-body energy homeostasis that coordinates metabolic pathways in order to balance nutrient supply with energy demand. It is now recognized that pharmacological activation of AMPK improves blood glucose homeostasis, lipid profile and blood pressure in insulin-resistant rodents. Indeed, AMPK activation mimics the beneficial effects of physical activity or those of calorie restriction by acting on multiple cellular targets. In addition it is now demonstrated that AMPK is one of the probable (albeit indirect) targets of major antidiabetic drugs including, the biguanides (metformin) and thiazolidinediones, as well as of insulin sensitizing adipokines (e.g., adiponectin). Taken together, such findings highlight the logic underlying the concept of targeting the AMPK pathway for the treatment of metabolic syndrome and type 2 diabetes. PMID:21484577

Physics Division progress report for period ending September 30, 1983

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

Not Available

1983-12-01

Research and development activities are summarized in the following areas: Holifield Heavy Ion Research Facility, nuclear physics, the UNISOR program, accelerator-based atomic physics, theoretical physics, nuclear science applications, atomic physics and plasma diagnostics for fusion program, high-energy physics, the nuclear data project, and the relativistic heavy-ion collider study. Publications and papers presented are listed. (WHK)

Mechanism of cAMP Partial Agonism in Protein Kinase G (PKG)*♦

PubMed Central

VanSchouwen, Bryan; Selvaratnam, Rajeevan; Giri, Rajanish; Lorenz, Robin; Herberg, Friedrich W.; Kim, Choel; Melacini, Giuseppe

2015-01-01

Protein kinase G (PKG) is a major receptor of cGMP and controls signaling pathways often distinct from those regulated by cAMP. Hence, the selective activation of PKG by cGMP versus cAMP is critical. However, the mechanism of cGMP-versus-cAMP selectivity is only limitedly understood. Although the C-terminal cyclic nucleotide-binding domain B of PKG binds cGMP with higher affinity than cAMP, the intracellular concentrations of cAMP are typically higher than those of cGMP, suggesting that the cGMP-versus-cAMP selectivity of PKG is not controlled uniquely through affinities. Here, we show that cAMP is a partial agonist for PKG, and we elucidate the mechanism for cAMP partial agonism through the comparative NMR analysis of the apo, cGMP-, and cAMP-bound forms of the PKG cyclic nucleotide-binding domain B. We show that although cGMP activation is adequately explained by a two-state conformational selection model, the partial agonism of cAMP arises from the sampling of a third, partially autoinhibited state. PMID:26370085

The Popeye Domain Containing Genes and Their Function in Striated Muscle

PubMed Central

Schindler, Roland F. R.; Scotton, Chiara; French, Vanessa; Ferlini, Alessandra; Brand, Thomas

2016-01-01

The Popeye domain containing (POPDC) genes encode a novel class of cAMP effector proteins, which are abundantly expressed in heart and skeletal muscle. Here, we will review their role in striated muscle as deduced from work in cell and animal models and the recent analysis of patients carrying a missense mutation in POPDC1. Evidence suggests that POPDC proteins control membrane trafficking of interacting proteins. Furthermore, we will discuss the current catalogue of established protein-protein interactions. In recent years, the number of POPDC-interacting proteins has been rising and currently includes ion channels (TREK-1), sarcolemma-associated proteins serving functions in mechanical stability (dystrophin), compartmentalization (caveolin 3), scaffolding (ZO-1), trafficking (NDRG4, VAMP2/3) and repair (dysferlin) or acting as a guanine nucleotide exchange factor for Rho-family GTPases (GEFT). Recent evidence suggests that POPDC proteins might also control the cellular level of the nuclear proto-oncoprotein c-Myc. These data suggest that this family of cAMP-binding proteins probably serves multiple roles in striated muscle. PMID:27347491

Atmospheric, Magnetospheric and Plasmas in space (AMPS) spacelab payload definition study. Volume 4. Part 1, AMPS program specification

NASA Technical Reports Server (NTRS)

Keeley, J. T.

1976-01-01

The AMPS Program Specification delineates the AMPS Program requirements consistent with the resources defined in the AMPS Project Plan. All subsidiary specifications and requirements shall conform to the requirements presented. The requirements hierarchy for the AMPS program is illustrated. A brief description of each of the requirements documents and their intended use is provided.

Role of 2′,3′-cyclic nucleotide 3′-phosphodiesterase in the renal 2′,3′-cAMP-adenosine pathway

PubMed Central

Gillespie, Delbert G.; Mi, Zaichuan; Cheng, Dongmei; Bansal, Rashmi; Janesko-Feldman, Keri; Kochanek, Patrick M.

2014-01-01

Energy depletion increases the renal production of 2′,3′-cAMP (a positional isomer of 3′,5′-cAMP that opens mitochondrial permeability transition pores) and 2′,3′-cAMP is converted to 2′-AMP and 3′-AMP, which in turn are metabolized to adenosine. Because the enzymes involved in this “2′,3′-cAMP-adenosine pathway” are unknown, we examined whether 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) participates in the renal metabolism of 2′,3′-cAMP. Western blotting and real-time PCR demonstrated expression of CNPase in rat glomerular mesangial, preglomerular vascular smooth muscle and endothelial, proximal tubular, thick ascending limb and collecting duct cells. Real-time PCR established the expression of CNPase in human glomerular mesangial, proximal tubular and vascular smooth muscle cells; and the level of expression of CNPase was greater than that for phosphodiesterase 4 (major enzyme for the metabolism of 3′,5′-cAMP). Overexpression of CNPase in rat preglomerular vascular smooth muscle cells increased the metabolism of exogenous 2′,3′-cAMP to 2′-AMP. Infusions of 2′,3′-cAMP into isolated CNPase wild-type (+/+) kidneys increased renal venous 2′-AMP, and this response was diminished by 63% in CNPase knockout (−/−) kidneys, whereas the conversion of 3′,5′-cAMP to 5′-AMP was similar in CNPase +/+ vs. −/− kidneys. In CNPase +/+ kidneys, energy depletion (metabolic poisons) increased kidney tissue levels of adenosine and its metabolites (inosine, hypoxanthine, xanthine, and uric acid) without accumulation of 2′,3′-cAMP. In contrast, in CNPase −/− kidneys, energy depletion increased kidney tissue levels of 2′,3′-cAMP and abolished the increase in adenosine and its metabolites. In conclusion, kidneys express CNPase, and renal CNPase mediates in part the renal 2′,3′-cAMP-adenosine pathway. PMID:24808540

Cyclic AMP- and (Rp)-cAMPS-induced Conformational Changes in a Complex of the Catalytic and Regulatory (RIα) Subunits of Cyclic AMP-dependent Protein Kinase*

PubMed Central

Anand, Ganesh S.; Krishnamurthy, Srinath; Bishnoi, Tanushree; Kornev, Alexandr; Taylor, Susan S.; Johnson, David A.

2010-01-01

We took a discovery approach to explore the actions of cAMP and two of its analogs, one a cAMP mimic ((Sp)-adenosine cyclic 3′:5′-monophosphorothioate ((Sp)-cAMPS)) and the other a diastereoisomeric antagonist ((Rp)-cAMPS), on a model system of the type Iα cyclic AMP-dependent protein kinase holoenzyme, RIα(91–244)·C-subunit, by using fluorescence spectroscopy and amide H/2H exchange mass spectrometry. Specifically, for the fluorescence experiments, fluorescein maleimide was conjugated to three cysteine single residue substitution mutants, R92C, T104C, and R239C, of RIα(91–244), and the effects of cAMP, (Sp)-cAMPS, and (Rp)-cAMPS on the kinetics of R-C binding and the time-resolved anisotropy of the reporter group at each conjugation site were measured. For the amide exchange experiments, ESI-TOF mass spectrometry with pepsin proteolytic fragmentation was used to assess the effects of (Rp)-cAMPS on amide exchange of the RIα(91–244)·C-subunit complex. We found that cAMP and its mimic perturbed at least parts of the C-subunit interaction Sites 2 and 3 but probably not Site 1 via reduced interactions of the linker region and αC of RIα(91–244). Surprisingly, (Rp)-cAMPS not only increased the affinity of RIα(91–244) toward the C-subunit by 5-fold but also produced long range effects that propagated through both the C- and R-subunits to produce limited unfolding and/or enhanced conformational flexibility. This combination of effects is consistent with (Rp)-cAMPS acting by enhancing the internal entropy of the R·C complex. Finally, the (Rp)-cAMPS-induced increase in affinity of RIα(91–244) toward the C-subunit indicates that (Rp)-cAMPS is better described as an inverse agonist because it decreases the fractional dissociation of the cyclic AMP-dependent protein kinase holoenzyme and in turn its basal activity. PMID:20167947

Cyclic AMP Enhances TGFβ Responses of Breast Cancer Cells by Upregulating TGFβ Receptor I Expression

PubMed Central

Oerlecke, Ilka; Bauer, Elke; Dittmer, Angela; Leyh, Benjamin; Dittmer, Jürgen

2013-01-01

Cellular functions are regulated by complex networks of many different signaling pathways. The TGFβ and cAMP pathways are of particular importance in tumor progression. We analyzed the cross-talk between these pathways in breast cancer cells in 2D and 3D cultures. We found that cAMP potentiated TGFβ-dependent gene expression by enhancing Smad3 phosphorylation. Higher levels of total Smad3, as observed in 3D-cultured cells, blocked this effect. Two Smad3 regulating proteins, YAP (Yes-associated protein) and TβRI (TGFβ receptor 1), were responsive to cAMP. While YAP had little effect on TGFβ-dependent expression and Smad3 phosphorylation, a constitutively active form of TβRI mimicked the cAMP effect on TGFβ signaling. In 3D-cultured cells, which show much higher levels of TβRI and cAMP, TβRI was unresponsive to cAMP. Upregulation of TβRI expression by cAMP was dependent on transcription. A proximal TβRI promoter fragment was moderately, but significantly activated by cAMP suggesting that cAMP increases TβRI expression at least partially by activating TβRI transcription. Neither the cAMP-responsive element binding protein (CREB) nor the TβRI-regulating transcription factor Six1 was required for the cAMP effect. An inhibitor of histone deacetylases alone or together with cAMP increased TβRI expression by a similar extent as cAMP alone suggesting that cAMP may exert its effect by interfering with histone acetylation. Along with an additive stimulatory effect of cAMP and TGFβ on p21 expression an additive inhibitory effect of these agents on proliferation was observed. Finally, we show that mesenchymal stem cells that interact with breast cancer cells can simultaneously activate the cAMP and TGFβ pathways. In summary, these data suggest that combined effects of cAMP and TGFβ, as e.g. induced by mesenchymal stem cells, involve the upregulation of TβRI expression on the transcriptional level, likely due to changes in histone acetylation. As a consequence, cancer cell functions such as proliferation are affected. PMID:23349840

Increase in Ca2+ current by sustained cAMP levels enhances proliferation rate in GH3 cells.

PubMed

Rodrigues, Andréia Laura; Brescia, Marcella; Koschinski, Andreas; Moreira, Thaís Helena; Cameron, Ryan T; Baillie, George; Beirão, Paulo S L; Zaccolo, Manuela; Cruz, Jader S

2018-01-01

Ca 2+ and cAMP are important intracellular modulators. In order to generate intracellular signals with various amplitudes, as well as different temporal and spatial properties, a tightly and precise control of these modulators in intracellular compartments is necessary. The aim of this study was to evaluate the effects of elevated and sustained cAMP levels on voltage-dependent Ca 2+ currents and proliferation in pituitary tumor GH3 cells. Effect of long-term exposure to forskolin and dibutyryl-cyclic AMP (dbcAMP) on Ca 2+ current density and cell proliferation rate were determined by using the whole-cell patch-clamp technique and real time cell monitoring system. The cAMP levels were assayed, after exposing transfected GH3 cells with the EPAC-1 cAMP sensor to forskolin and dbcAMP, by FRET analysis. Sustained forskolin treatment (24 and 48h) induced a significant increase in total Ca 2+ current density in GH3 cells. Accordingly, dibutyryl-cAMP incubation (dbcAMP) also elicited increase in Ca 2+ current density. However, the maximum effect of dbcAMP occurred only after 72h incubation, whereas forskolin showed maximal effect at 48h. FRET-experiments confirmed that the time-course to elevate intracellular cAMP was distinct between forskolin and dbcAMP. Mibefradil inhibited the fast inactivating current component selectively, indicating the recruitment of T-type Ca 2+ channels. A significant increase on cell proliferation rate, which could be related to the elevated and sustained intracellular levels of cAMP was observed. We conclude that maintaining high levels of intracellular cAMP will cause an increase in Ca 2+ current density and this phenomenon impacts proliferation rate in GH3 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

5D imaging approaches reveal the formation of distinct intracellular cAMP spatial gradients

NASA Astrophysics Data System (ADS)

Rich, Thomas C.; Annamdevula, Naga; Trinh, Kenny; Britain, Andrea L.; Mayes, Samuel A.; Griswold, John R.; Deal, Joshua; Hoffman, Chase; West, Savannah; Leavesley, Silas J.

2017-02-01

Cyclic AMP (cAMP) is a ubiquitous second messenger known to differentially regulate many cellular functions. Several lines of evidence suggest that the distribution of cAMP within cells is not uniform. However, to date, no studies have measured the kinetics of 3D cAMP distributions within cells. This is largely due to the low signal-tonoise ratio of FRET-based probes. We previously reported that hyperspectral imaging improves the signal-to-noise ratio of FRET measurements. Here we utilized hyperspectral imaging approaches to measure FRET signals in five dimensions (5D) - three spatial (x, y, z), wavelength (λ), and time (t) - allowing us to visualize cAMP gradients in pulmonary endothelial cells. cAMP levels were measured using a FRET-based sensor (H188) comprised of a cAMP binding domain sandwiched between FRET donor and acceptor - Turquoise and Venus fluorescent proteins. We observed cAMP gradients in response to 0.1 or 1 μM isoproterenol, 0.1 or 1 μM PGE1, or 50 μM forskolin. Forskolin- and isoproterenol-induced cAMP gradients formed from the apical (high cAMP) to basolateral (low cAMP) face of cells. In contrast, PGE1-induced cAMP gradients originated from both the basolateral and apical faces of cells. Data suggest that 2D (x,y) studies of cAMP compartmentalization may lead to erroneous conclusions about the existence of cAMP gradients, and that 3D (x,y,z) studies are required to assess mechanisms of signaling specificity. Results demonstrate that 5D imaging technologies are powerful tools for measuring biochemical processes in discrete subcellular domains.

Inhibition of basolateral cAMP permeability in the toad urinary bladder.

PubMed

Boom, A; Golstein, P E; Frerotte, M; Sande, J V; Beauwens, R

2000-10-01

1. The effect of sulphonylurea drugs on hydrosmotic flow across toad urinary bladder epithelium was re-evaluated in the present study. Glibenclamide, added to the basolateral medium, significantly enhanced the osmotic flow induced by low doses of antidiuretic hormone (ADH) or forskolin (FK), while it inhibited the effect of exogenous cyclic adenosine monophosphate (cAMP) or its non-hydrolysable bromo derivative, 8-Br-cAMP, added to the basolateral medium. These opposite effects of glibenclamide on the transepithelial osmotic flow can be explained by a reduction of cAMP permeability across the basolateral membrane of the epithelium. The decrease in cAMP permeability leads, according to the direction of the cAMP gradient, to firstly an enhanced osmotic flow when cAMP is generated intracellularly by addition of ADH and FK, glibenclamide reducing cAMP exit from the cell, and secondly a decreased osmotic flow in response to cAMP (and 8-Br-cAMP) added to the basolateral medium, glibenclamide inhibiting, in this case, their entry into the cell. 2. The demonstration that glibenclamide actually inhibits the basolateral cAMP permeability rests on the fact that firstly it decreases the release of cAMP into the basolateral medium by about 40 %, at each concentration of ADH or forskolin tested, secondly it increases the cAMP content of paired hemibladders incubated in the presence of ADH or FK, when intracellular degradation was prevented by phosphodiesterase inhibition, and thirdly it decreases also the uptake of basolateral 8-Br-[3H]cAMP into paired toad hemibladders. 3. Taken together, the present data demonstrate that glibenclamide inhibits the toad urinary bladder basolateral membrane permeability to cAMP, most probably by a direct interaction with a membrane protein not yet indentified but distinct from the sulphonylurea receptor.

AmpA protein functions by different mechanisms to influence early cell type specification and to modulate cell adhesion and actin polymerization in Dictyostelium discoideum

PubMed Central

Cost, Hoa N.; Noratel, Elizabeth F.; Blumberg, Daphne D.

2013-01-01

The Dictyostelium discoideum ampA gene encodes a multifunctional regulator protein that modulates cell–cell and cell–substrate adhesions and actin polymerization during growth and is necessary for correct cell type specification and patterning during development. Insertional inactivation of the ampA gene results in defects that define two distinct roles for the ampA gene during development. AmpA is necessary in a non-cell autonomous manner to prevent premature expression of a prespore gene marker. It is also necessary in a cell autonomous manner for the anterior like cells, which express the ampA gene, to migrate to the upper cup during culmination. It is also necessary to prevent excessive cell–cell agglutination when cells are developed in a submerged suspension culture. Here, we demonstrate that a supernatant source of AmpA protein, added extracellularly, can prevent the premature mis-expression of the prespore marker. Synthetic oligopeptides are used to identify the domain of the AmpA protein that is important for preventing cells from mis-expressing the prespore gene. We further demonstrate that a factor capable of inducing additional cells to express the prespore gene marker accumulates extracellularly in the absence of AmpA protein. While the secreted AmpA acts extracellularly to suppress prespore gene expression, the effects of AmpA on cell agglutination and on actin polymerization in growing cells are not due to an extracellular role of secreted AmpA protein. Rather, these effects appear to reflect a distinct cell autonomous role of the ampA gene. Finally, we show that secretion of AmpA protein is brought about by elevating the levels of expression of ampA so that the protein accumulates to an excessive level. PMID:23911723

Parallel Allostery by cAMP and PDE Coordinates Activation and Termination Phases in cAMP Signaling.

PubMed

Krishnamurthy, Srinath; Tulsian, Nikhil Kumar; Chandramohan, Arun; Anand, Ganesh S

2015-09-15

The second messenger molecule cAMP regulates the activation phase of the cAMP signaling pathway through high-affinity interactions with the cytosolic cAMP receptor, the protein kinase A regulatory subunit (PKAR). Phosphodiesterases (PDEs) are enzymes responsible for catalyzing hydrolysis of cAMP to 5' AMP. It was recently shown that PDEs interact with PKAR to initiate the termination phase of the cAMP signaling pathway. While the steps in the activation phase are well understood, steps in the termination pathway are unknown. Specifically, the binding and allosteric networks that regulate the dynamic interplay between PKAR, PDE, and cAMP are unclear. In this study, PKAR and PDE from Dictyostelium discoideum (RD and RegA, respectively) were used as a model system to monitor complex formation in the presence and absence of cAMP. Amide hydrogen/deuterium exchange mass spectrometry was used to monitor slow conformational transitions in RD, using disordered regions as conformational probes. Our results reveal that RD regulates its interactions with cAMP and RegA at distinct loci by undergoing slow conformational transitions between two metastable states. In the presence of cAMP, RD and RegA form a stable ternary complex, while in the absence of cAMP they maintain transient interactions. RegA and cAMP each bind at orthogonal sites on RD with resultant contrasting effects on its dynamics through parallel allosteric relays at multiple important loci. RD thus serves as an integrative node in cAMP termination by coordinating multiple allosteric relays and governing the output signal response. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Fibroblast growth factor and cyclic AMP (cAMP) synergistically activate gene expression at a cAMP response element.

PubMed Central

Tan, Y; Low, K G; Boccia, C; Grossman, J; Comb, M J

1994-01-01

Growth factors and cyclic AMP (cAMP) are known to activate distinct intracellular signaling pathways. Fibroblast growth factor (FGF) activates ras-dependent kinase cascades, resulting in the activation of MAP kinases, whereas cAMP activates protein kinase A. In this study, we report that growth factors and cAMP act synergistically to stimulate proenkephalin gene expression. Positive synergy between growth factor- and cAMP-activated signaling pathways on gene expression has not been previously reported, and we suggest that these synergistic interactions represent a useful model for analyzing interactions between these pathways. Transfection and mutational studies indicate that both FGF-dependent gene activation and cAMP-dependent gene activation require cAMP response element 2 (CRE-2), a previously characterized cAMP-dependent regulatory element. Furthermore, multiple copies of this element are sufficient to confer FGF regulation upon a minimal promoter, indicating that FGF and cAMP signaling converge upon transcription factors acting at CRE-2. Among many different ATF/AP-1 factors tested, two factors, ATF-3 and c-Jun, stimulate proenkephalin transcription in an FGF- or Ras-dependent fashion. Finally, we show that ATF-3 and c-Jun form heterodimeric complexes in SK-N-MC cells and that the levels of both proteins are increased in response to FGF but not cAMP. Together, these results indicate that growth factor- and cAMP-dependent signaling pathways converge at CRE-2 to synergistically stimulate gene expression and that ATF-3 and c-Jun regulate proenkephalin transcription in response to both growth factor- and cAMP-dependent intracellular signaling pathways. Images PMID:7935470

The cAMP analogs have potent anti-proliferative effects on medullary thyroid cancer cell lines.

PubMed

Dicitore, Alessandra; Grassi, Elisa Stellaria; Caraglia, Michele; Borghi, Maria Orietta; Gaudenzi, Germano; Hofland, Leo J; Persani, Luca; Vitale, Giovanni

2016-01-01

The oncogenic activation of the rearranged during transfection (RET) proto-oncogene has a main role in the pathogenesis of medullary thyroid cancer (MTC). Several lines of evidence suggest that RET function could be influenced by cyclic AMP (cAMP)-dependent protein kinase A (PKA) activity. We evaluated the in vitro anti-tumor activity of 8-chloroadenosine-3',5'-cyclic monophosphate (8-Cl-cAMP) and PKA type I-selective cAMP analogs [equimolar combination of the 8-piperidinoadenosine-3',5'-cyclic monophosphate (8-PIP-cAMP) and 8-hexylaminoadenosine-3',5'-cyclic monophosphate (8-HA-cAMP) in MTC cell lines (TT and MZ-CRC-1)]. 8-Cl-cAMP and the PKA I-selective cAMP analogs showed a potent anti-proliferative effect in both cell lines. In detail, 8-Cl-cAMP blocked significantly the transition of TT cell population from G2/M to G0/G1 phase and from G0/G1 to S phase and of MZ-CRC-1 cells from G0/G1 to S phase. Moreover, 8-Cl-cAMP induced apoptosis in both cell lines, as demonstrated by FACS analysis for annexin V-FITC/propidium iodide, the activation of caspase-3 and PARP cleavage. On the other hand, the only effect induced by PKA I-selective cAMP analogs was a delay in G0/G1-S and S-G2/M progression in TT and MZ-CRC-1 cells, respectively. In conclusion, these data demonstrate that cAMP analogs, particularly 8-Cl-cAMP, significantly suppress in vitro MTC proliferation and provide rationale for a potential clinical use of cAMP analogs in the treatment of advanced MTC.

Handbook explaining the fundamentals of nuclear and atomic physics

NASA Technical Reports Server (NTRS)

Hanlen, D. F.; Morse, W. J.

1969-01-01

Indoctrination document presents nuclear, reactor, and atomic physics in an easy, straightforward manner. The entire subject of nuclear physics including atomic structure ionization, isotopes, radioactivity, and reactor dynamics is discussed.

Atmospheric, Magnetospheric and Plasmas in Space (AMPS) spacelab payload definition study. Volume 3: Interface control documents. Part 2: AMPS payload to spacelab ICD

NASA Technical Reports Server (NTRS)

1976-01-01

The AMPS to Spacelab Interface Control Document which is to be used as a guide for format and information content in generating specific AMPS Mission ICDs is presented. This document is meant to supplement the Spacelab Payload Accommodations Handbook in that it only defines interfaces which are not discussed in the handbook to the level required for design purposes. The AMPS Top Level Requirements Tree, illustrates this ICD by a shaded area and its relationship to the other AMPS technical documents. Other interface documents shown are the Level II, AMPS to Space Shuttle Vehicle ICD and the Level III, AMPS to Instruments ICD.

Regulation of Maltodextrin Phosphorylase Synthesis in Escherichia coli by Cyclic Adenosine 3′, 5′-Monophosphate and Glucose1

PubMed Central

Chao, Julie; Weathersbee, Carolyn J.

1974-01-01

Cyclic adenosine 3′, 5′-monophosphate (AMP) stimulates maltodextrin phosphorylase synthesis in Escherichia coli cells induced with maltose. A maximal effect occurs at 2 to 3 mM cyclic AMP. The action of cyclic AMP is specific, inasmuch as adenosine triphosphate, 3′-AMP, 5′-AMP, adenosine, and dibutyryl cyclic AMP are inactive. Glucose, α-methyl glucoside, 2-deoxyglucose, and pyridoxal 5′-phosphate repress maltodextrin phosphorylase synthesis. This repression is reversed by cyclic AMP. The action of cyclic AMP appears to be at the transcriptional level, since cyclic AMP fails to stimulate phosphorylase production in induced cells in which messenger ribonucleic acid synthesis has been arrested by rifampin or by inducer removal. The two other enzymes involved in the metabolism of maltose, amylomaltase and maltose permease, are also induced in this strain of E. coli and affected by glucose and cyclic AMP in a manner similar to phosphorylase. PMID:4358043

Epigenetic Regulation of the NR4A Orphan Nuclear Receptor NOR1 By Histone Acetylation

PubMed Central

Zhao, Yue; Nomiyama, Takashi; Findeisen, Hannes M.; Qing, Hua; Aono, Jun; Jones, Karrie L.; Heywood, Elizabeth B.; Bruemmer, Dennis

2014-01-01

The nuclear receptor NOR1 is an immediate-early response gene implicated in the transcriptional control of proliferation. Since the expression level of NOR1 is rapidly induced through cAMP response element binding (CREB) protein-dependent promoter activation, we investigated the contribution of histone acetylation to this transient induction. We demonstrate that NOR1 transcription is induced by histone deacetylase (HDAC) inhibition and by depletion of HDAC1 and HDAC3. HDAC inhibition activated the NOR1 promoter, increased histone acetylation and augmented the recruitment of phosphorylated CREB to the promoter. Furthermore, HDAC inhibition increased Ser133 phosphorylation of CREB and augmented NOR1 protein stability. These data outline previously unrecognized mechanisms of NOR1 regulation and illustrate a key role for histone acetylation in the rapid induction of NOR1. PMID:25451221

Voluntary Running Depreciates the Requirement of Ca[superscript 2+]-Stimulated cAMP Signaling in Synaptic Potentiation and Memory Formation

ERIC Educational Resources Information Center

Zheng, Fei; Zhang, Ming; Ding, Qi; Sethna, Ferzin; Yan, Lily; Moon, Changjong; Yang, Miyoung; Wang, Hongbing

2016-01-01

Mental health and cognitive functions are influenced by both genetic and environmental factors. Although having active lifestyle with physical exercise improves learning and memory, how it interacts with the specific key molecular regulators of synaptic plasticity is largely unknown. Here, we examined the effects of voluntary running on long-term…

Adsorption characteristics of green 5-arylaminomethylene pyrimidine-2,4,6-triones on mild steel surface in acidic medium: Experimental and computational approach

NASA Astrophysics Data System (ADS)

Verma, Chandrabhan; Olasunkanmi, Lukman O.; Ebenso, Eno E.; Quraishi, M. A.

2018-03-01

The effect of electron withdrawing nitro (-NO2) and electron releasing hydroxyl (-OH) groups on corrosion inhibition potentials of 5-arylaminomethylenepyrimidine-2,4,6-trione (AMP) had been studied. Four AMPs tagged AMP-1, AMP-2, AMP-3 and AMP-4 were studied for their ability to inhibit mild steel corrosion in 1 M HCl using experimental and theoretical methods. Gravimetric results showed that inhibition efficiency of the studied inhibitors increases with increasing concentration. The results further revealed that that electron withdrawing nitro (-NO2) group decreases the inhibition efficiency of AMP, while electron donating hydroxyl (-OH) group increases the inhibition efficiency of AMP. SEM and AFM studies showed that the studied compounds inhibit mild steel corrosion by adsorbing at the metal/electrolyte interface and their adsorption obeyed the Temkin adsorption isotherm. Potentiodynamic polarization study revealed that studied inhibitors act as mixed type inhibitors with predominant effect on cathodic reaction. The inhibitive strength of the compounds might have direct relationship electron donating ability of the molecules as revealed by quantum chemical parameters. The order of interaction energies derived from Monte Carlo simulations is AMP-4 > AMP-3 > AMP-2 > AMP-1, which is in agreement with the order of inhibition efficiencies obtained from experimental measurements.

Gene Expression Patterns Define Key Transcriptional Events InCell-Cycle Regulation By cAMP And Protein Kinase A

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

Zambon, Alexander C.; Zhang, Lingzhi; Minovitsky, Simon

Although a substantial number of hormones and drugs increase cellular cAMP levels, the global impact of cAMP and its major effector mechanism, protein kinase A (PKA), on gene expression is not known. Here we show that treatment of murine wild-type S49 lymphoma cells for 24 h with 8-(4-chlorophenylthio)-cAMP (8-CPTcAMP), a PKA-selective cAMP analog, alters the expression of approx equal to 4,500 of approx. equal to 13,600 unique genes. By contrast, gene expression was unaltered in Kin- S49 cells (that lack PKA) incubated with 8-CPTcAMP. Changes in mRNA and protein expression of several cell cycle regulators accompanied cAMP-induced G1-phase cell-cycle arrestmore » of wild-type S49 cells. Within 2h, 8-CPT-cAMP altered expression of 152 genes that contain evolutionarily conserved cAMP-response elements within 5 kb of transcriptional start sites, including the circadian clock gene Per1. Thus, cAMP through its activation of PKA produces extensive transcriptional regulation in eukaryotic cells. These transcriptional networks include a primary group of cAMP-response element-containing genes and secondary networks that include the circadian clock.« less

Cyclic AMP efflux inhibitors as potential therapeutic agents for leukemia.

PubMed

Perez, Dominique R; Smagley, Yelena; Garcia, Matthew; Carter, Mark B; Evangelisti, Annette; Matlawska-Wasowska, Ksenia; Winter, Stuart S; Sklar, Larry A; Chigaev, Alexandre

2016-06-07

Apoptotic evasion is a hallmark of cancer. We propose that some cancers may evade cell death by regulating 3'-5'-cyclic adenosine monophosphate (cAMP), which is associated with pro-apoptotic signaling. We hypothesize that leukemic cells possess mechanisms that efflux cAMP from the cytoplasm, thus protecting them from apoptosis. Accordingly, cAMP efflux inhibition should result in: cAMP accumulation, activation of cAMP-dependent downstream signaling, viability loss, and apoptosis. We developed a novel assay to assess cAMP efflux and performed screens to identify inhibitors. In an acute myeloid leukemia (AML) model, several identified compounds reduced cAMP efflux, appropriately modulated pathways that are responsive to cAMP elevation (cAMP-responsive element-binding protein phosphorylation, and deactivation of Very Late Antigen-4 integrin), and induced mitochondrial depolarization and caspase activation. Blocking adenylyl cyclase activity was sufficient to reduce effects of the most potent compounds. These compounds also decreased cAMP efflux and viability of B-lineage acute lymphoblastic leukemia (B-ALL) cell lines and primary patient samples, but not of normal primary peripheral blood mononuclear cells. Our data suggest that cAMP efflux is a functional feature that could be therapeutically targeted in leukemia. Furthermore, because some of the identified drugs are currently used for treating other illnesses, this work creates an opportunity for repurposing.

Dual contradictory roles of cAMP signaling pathways in hydroxyl radical production in the rat striatum.

PubMed

Hara, Shuichi; Kobayashi, Masamune; Kuriiwa, Fumi; Mukai, Toshiji; Mizukami, Hajime

2012-03-15

Studies have suggested that cAMP signaling pathways may be associated with the production of reactive oxygen species. In this study, we examined how modifications in cAMP signaling affected the production of hydroxyl radicals in rat striatum using microdialysis to measure extracellular 2,3-dihydroxybenzoic acid (2,3-DHBA), which is a hydroxyl radical adduct of salicylate. Up to 50 nmol of the cell-permeative cAMP mimetic 8-bromo-cAMP (8-Br-cAMP) increased 2,3-DHBA in a dose-dependent manner (there was no additional increase in 2,3-DHBA at 100 nmol). Another cAMP mimetic, dibutyryl cAMP (db-cAMP), caused a nonsignificant increase in 2,3-DHBA at 50 nmol and a significant decrease at 100 nmol. Up to 20 nmol of forskolin, which is a direct activator of adenylyl cyclase, increased 2,3-DHBA, similar to the effect of 8-Br-cAMP; however, forskolin resulted in a much greater increase in 2,3-DHBA. A potent inhibitor of protein kinase A (PKA), H89 (500 μM), potentiated the 8-Br-cAMP- and forskolin-induced increases in 2,3-DHBA and antagonized the inhibitory effect of 100 nmol of db-cAMP. Interestingly, the administration of 100 nmol of 8-bromo-cGMP alone or in combination with H89 had no significant effect on 2,3-DHBA levels. Doses of 100 nmol of a preferential PKA activator (6-phenyl-cAMP) or a preferential PKA inhibitor (8-bromoadenosine-3',5'-cyclic monophosphorothionate, Rp-isomer; Rp-8-Br-cAMPS), which also inhibits the cAMP-mediated activation of Epac (the exchange protein directly activated by cAMP), suppressed or enhanced, respectively, the formation of 2,3-DHBA. Up to 100 nmol of 8-(4-chlorophenylthio)-2'-O-methyladenosine-cAMP, which is a selective activator of Epac, dose-dependently stimulated the formation of 2,3-DHBA. These findings suggest that cAMP signaling plays contradictory roles (stimulation and inhibition) in the production of hydroxyl radicals in rat striatum by differential actions of Epac and PKA. These roles might contribute to the production of hydroxyl radicals concomitant with cAMP in carbon monoxide poisoning, because the formation of 2,3-DHBA was potentiated by the PKA inhibitor H89 and suppressed by Rp-8-Br-cAMPS, which inhibits PKA and Epac. Copyright © 2012 Elsevier Inc. All rights reserved.

Sulfur dioxide inhibits vascular smooth muscle cell proliferation via suppressing the Erk/MAP kinase pathway mediated by cAMP/PKA signaling

PubMed Central

Liu, D; Huang, Y; Bu, D; Liu, A D; Holmberg, L; Jia, Y; Tang, C; Du, J; Jin, H

2014-01-01

The present study was designed to investigate the role of endogenous sulfur dioxide (SO2) in vascular smooth muscle cell (VSMC) proliferation, and explore the possible role of cross-talk between cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) pathways in this action. By cell counting, growth curve depict, flow cytometry and bromodeoxyuridine (BrdU) labeling assays, we found that SO2 inhibited VSMC proliferation by preventing cell cycle progression from G1 to S phase and by reducing DNA synthesis. SO2 synthase aspartate aminotransferase (AAT1 and AAT2) overexpression significantly inhibited serum-induced proliferating cell nuclear antigen (PCNA) protein expression in VSMCs, demonstrated by western blot analysis. Moreover, overexpression of AAT1 or AAT2 markedly reduced incorporation of BrdU in serum-treated VSMCs. By contrast, either AAT1 or AAT2 knockdown significantly exacerbated serum-stimulated VSMC proliferation. Thus, both exogenous- and endogenous-derived SO2 suppressed serum-induced VSMC proliferation. However, annexin V-propidium iodide (PI) staining and cell cycle analysis demonstrated that SO2 did not influence VSMC apoptosis in the serum-induced proliferation model. In a platelet-derived growth factor (PDGF)-BB-stimulated VSMC proliferation model, SO2 dephosphorylated the active sites of Erk1/2, MAPK kinase 1/2 and RAF proto-oncogene serine/threonine-protein kinase (c-Raf) induced by PDGF-BB. However, the inactivation of the three kinases of the Erk/MAPK pathway was not due to the separate interferences on them by SO2 simultaneously, but a consequence of the influence on the upstream activity of the c-Raf molecule. Hence, we examined the cAMP/PKA pathway, which could inhibit Erk/MAPK transduction in VSMCs. The results showed that SO2 could stimulate the cAMP/PKA pathway to block c-Raf activation, whereas the Ser259 site on c-Raf had an important role in SO2-induced suppression of Erk/MAPK pathway. The present study firstly demonstrated that SO2 exerted a negative regulation of VSMC proliferation via suppressing the Erk/MAPK pathway mediated by cAMP/PKA signaling. PMID:24853429

Permanent Disposal of Nuclear Waste in Salt

NASA Astrophysics Data System (ADS)

Hansen, F. D.

2016-12-01

Salt formations hold promise for eternal removal of nuclear waste from our biosphere. Germany and the United States have ample salt formations for this purpose, ranging from flat-bedded formations to geologically mature dome structures. Both nations are revisiting nuclear waste disposal options, accompanied by extensive collaboration on applied salt repository research, design, and operation. Salt formations provide isolation while geotechnical barriers reestablish impermeability after waste is placed in the geology. Between excavation and closure, physical, mechanical, thermal, chemical, and hydrological processes ensue. Salt response over a range of stress and temperature has been characterized for decades. Research practices employ refined test techniques and controls, which improve parameter assessment for features of the constitutive models. Extraordinary computational capabilities require exacting understanding of laboratory measurements and objective interpretation of modeling results. A repository for heat-generative nuclear waste provides an engineering challenge beyond common experience. Long-term evolution of the underground setting is precluded from direct observation or measurement. Therefore, analogues and modeling predictions are necessary to establish enduring safety functions. A strong case for granular salt reconsolidation and a focused research agenda support salt repository concepts that include safety-by-design. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000. Author: F. D. Hansen, Sandia National Laboratories

21 CFR 890.5880 - Multi-function physical therapy table.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Multi-function physical therapy table. 890.5880 Section 890.5880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5880 Multi...

21 CFR 890.5880 - Multi-function physical therapy table.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Multi-function physical therapy table. 890.5880 Section 890.5880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5880 Multi...

21 CFR 890.5880 - Multi-function physical therapy table.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Multi-function physical therapy table. 890.5880 Section 890.5880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5880 Multi...

21 CFR 890.5880 - Multi-function physical therapy table.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Multi-function physical therapy table. 890.5880 Section 890.5880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5880 Multi...

21 CFR 890.5880 - Multi-function physical therapy table.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Multi-function physical therapy table. 890.5880 Section 890.5880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5880 Multi...

Improvements to Nuclear Data and Its Uncertainties by Theoretical Modeling

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

Danon, Yaron; Nazarewicz, Witold; Talou, Patrick

2013-02-18

This project addresses three important gaps in existing evaluated nuclear data libraries that represent a significant hindrance against highly advanced modeling and simulation capabilities for the Advanced Fuel Cycle Initiative (AFCI). This project will: Develop advanced theoretical tools to compute prompt fission neutrons and gamma-ray characteristics well beyond average spectra and multiplicity, and produce new evaluated files of U and Pu isotopes, along with some minor actinides; Perform state-of-the-art fission cross-section modeling and calculations using global and microscopic model input parameters, leading to truly predictive fission cross-sections capabilities. Consistent calculations for a suite of Pu isotopes will be performed; Implementmore » innovative data assimilation tools, which will reflect the nuclear data evaluation process much more accurately, and lead to a new generation of uncertainty quantification files. New covariance matrices will be obtained for Pu isotopes and compared to existing ones. The deployment of a fleet of safe and efficient advanced reactors that minimize radiotoxic waste and are proliferation-resistant is a clear and ambitious goal of AFCI. While in the past the design, construction and operation of a reactor were supported through empirical trials, this new phase in nuclear energy production is expected to rely heavily on advanced modeling and simulation capabilities. To be truly successful, a program for advanced simulations of innovative reactors will have to develop advanced multi-physics capabilities, to be run on massively parallel super- computers, and to incorporate adequate and precise underlying physics. And all these areas have to be developed simultaneously to achieve those ambitious goals. Of particular interest are reliable fission cross-section uncertainty estimates (including important correlations) and evaluations of prompt fission neutrons and gamma-ray spectra and uncertainties.« less

Discovery of novel antimicrobial peptides with unusual cysteine motifs in dandelion Taraxacum officinale Wigg. flowers.

PubMed

Astafieva, A A; Rogozhin, E A; Odintsova, T I; Khadeeva, N V; Grishin, E V; Egorov, Ts A

2012-08-01

Three novel antimicrobial peptides designated ToAMP1, ToAMP2 and ToAMP3 were purified from Taraxacum officinale flowers. Their amino acid sequences were determined. The peptides are cationic and cysteine-rich and consist of 38, 44 and 42 amino acid residues for ToAMP1, ToAMP2 and ToAMP3, respectively. Importantly, according to cysteine motifs, the peptides are representatives of two novel previously unknown families of plant antimicrobial peptides. ToAMP1 and ToAMP2 share high sequence identity and belong to 6-Cys-containing antimicrobial peptides, while ToAMP3 is a member of a distinct 8-Cys family. The peptides were shown to display high antimicrobial activity both against fungal and bacterial pathogens, and therefore represent new promising molecules for biotechnological and medicinal applications. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

A continuous spectrophotometric assay for monitoring adenosine 5'-monophosphate production.

PubMed

First, Eric A

2015-08-15

A number of biologically important enzymes release adenosine 5'-monophosphate (AMP) as a product, including aminoacyl-tRNA synthetases, cyclic AMP (cAMP) phosphodiesterases, ubiquitin and ubiquitin-like ligases, DNA ligases, coenzyme A (CoA) ligases, polyA deadenylases, and ribonucleases. In contrast to the abundance of assays available for monitoring the conversion of adenosine 5'-triphosphate (ATP) to ADP, there are relatively few assays for monitoring the conversion of ATP (or cAMP) to AMP. In this article, we describe a homogeneous assay that continuously monitors the production of AMP. Specifically, we have coupled the conversion of AMP to inosine 5'-monophosphate (IMP) (by AMP deaminase) to the oxidation of IMP (by IMP dehydrogenase). This results in the reduction of oxidized nicotine adenine dinucleotide (NAD(+)) to reduced nicotine adenine dinucleotide (NADH), allowing AMP formation to be monitored by the change in the absorbance at 340 nm. Changes in AMP concentrations of 5 μM or more can be reliably detected. The ease of use and relatively low expense make the AMP assay suitable for both high-throughput screening and kinetic analyses. Copyright © 2015 Elsevier Inc. All rights reserved.

A novel cysteine-rich antifungal peptide ToAMP4 from Taraxacum officinale Wigg. flowers.

PubMed

Astafieva, A A; Rogozhin, Eugene A; Andreev, Yaroslav A; Odintsova, T I; Kozlov, S A; Grishin, Eugene V; Egorov, Tsezi A

2013-09-01

A novel peptide named ToAMP4 was isolated from Taraxacum officinale Wigg. flowers by a combination of acetic acid extraction and different types of chromatography: affinity, size-exclusion, and RP-HPLC. The amino acid sequence of ToAMP4 was determined by automated Edman degradation. The peptide is basic, consists of 41 amino acids, and incorporates three disulphide bonds. Due to the unusual cysteine spacing pattern, ToAMP4 does not belong to any known plant AMP family, but classifies together with two other antimicrobial peptides ToAMP1 and ToAMP2 previously isolated from the dandelion flowers. To study the biological activity of ToAMP4, it was successfully produced in a prokaryotic expression system as a fusion protein with thioredoxin. The recombinant peptide was shown to be identical to the native ToAMP4 by chromatographic behavior, molecular mass, and N-terminal amino acid sequence. The peptide displays broad-spectrum antifungal activity against important phytopathogens. Two ToAMP4-mediated inhibition strategies depending on the fungus were demonstrated. The results obtained add to our knowledge on the structural and functional diversity of AMPs in plants. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

AMP Is an Adenosine A1 Receptor Agonist*

PubMed Central

Rittiner, Joseph E.; Korboukh, Ilia; Hull-Ryde, Emily A.; Jin, Jian; Janzen, William P.; Frye, Stephen V.; Zylka, Mark J.

2012-01-01

Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5′-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5′-monophosphonate, ACP) directly activated the adenosine A1 receptor (A1R). In contrast, AMP only activated the adenosine A2B receptor (A2BR) after hydrolysis to adenosine by ecto-5′-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A1R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A1R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A1R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A1R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine. PMID:22215671

AMP is an adenosine A1 receptor agonist.

PubMed

Rittiner, Joseph E; Korboukh, Ilia; Hull-Ryde, Emily A; Jin, Jian; Janzen, William P; Frye, Stephen V; Zylka, Mark J

2012-02-17

Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5'-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5'-monophosphonate, ACP) directly activated the adenosine A(1) receptor (A(1)R). In contrast, AMP only activated the adenosine A(2B) receptor (A(2B)R) after hydrolysis to adenosine by ecto-5'-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A(1)R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A(1)R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A(1)R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A(1)R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine.

Teaching Nuclear Physics in a General Education Curriculum

NASA Astrophysics Data System (ADS)

Lesher, Shelly R.

2017-01-01

The general public is unaware how physics shapes the world. This is especially true for nuclear physics, where many people are scared of the words ``nuclear'' and ``radiation''. To combat these perceptions, the Physics Department at the University of Wisconsin - La Crosse teaches a general education class on nuclear weapons, energy, and policy in society. This includes the social, economic, cultural, and political aspects surrounding the development of nuclear weapons and their place in the world, especially in current events. This talk will discuss the course, how it has grown, and sample student responses.

Final Technical Report for "Nuclear Technologies for Near Term Fusion Devices"

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

Wilson, Paul P.H.; Sawan, Mohamed E.; Davis, Andrew

Over approximately 18 years, this project evolved to focus on a number of related topics, all tied to the nuclear analysis of fusion energy systems. For the earliest years, the University of Wisconsin (UW)’s effort was in support of the Advanced Power Extraction (APEX) study to investigate high power density first wall and blanket systems. A variety of design concepts were studied before this study gave way to a design effort for a US Test Blanket Module (TBM) to be installed in ITER. Simultaneous to this TBM project, nuclear analysis supported the conceptual design of a number of fusion nuclearmore » science facilities that might fill a role in the path to fusion energy. Beginning in approximately 2005, this project added a component focused on the development of novel radiation transport software capability in support of the above nuclear analysis needs. Specifically, a clear need was identified to support neutron and photon transport on the complex geometries associated with Computer-Aided Design (CAD). Following the initial development of the Direct Accelerated Geoemtry Monte Carlo (DAGMC) capability, additional features were added, including unstructured mesh tallies and multi-physics analysis such as the Rigorous 2-Step (R2S) methodology for Shutdown Dose Rate (SDR) prediction. Throughout the project, there were also smaller tasks in support of the fusion materials community and for the testing of changes to the nuclear data that is fundamental to this kind of nuclear analysis.« less

Public health and medical preparedness for a nuclear detonation: the nuclear incident medical enterprise.

PubMed

Coleman, C Norman; Sullivan, Julie M; Bader, Judith L; Murrain-Hill, Paula; Koerner, John F; Garrett, Andrew L; Weinstock, David M; Case, Cullen; Hrdina, Chad; Adams, Steven A; Whitcomb, Robert C; Graeden, Ellie; Shankman, Robert; Lant, Timothy; Maidment, Bert W; Hatchett, Richard C

2015-02-01

Resilience and the ability to mitigate the consequences of a nuclear incident are enhanced by (1) effective planning, preparation and training; (2) ongoing interaction, formal exercises, and evaluation among the sectors involved; (3) effective and timely response and communication; and (4) continuous improvements based on new science, technology, experience, and ideas. Public health and medical planning require a complex, multi-faceted systematic approach involving federal, state, local, tribal, and territorial governments; private sector organizations; academia; industry; international partners; and individual experts and volunteers. The approach developed by the U.S. Department of Health and Human Services Nuclear Incident Medical Enterprise (NIME) is the result of efforts from government and nongovernment experts. It is a "bottom-up" systematic approach built on the available and emerging science that considers physical infrastructure damage, the spectrum of injuries, a scarce resources setting, the need for decision making in the face of a rapidly evolving situation with limited information early on, timely communication, and the need for tools and just-in-time information for responders who will likely be unfamiliar with radiation medicine and uncertain and overwhelmed in the face of the large number of casualties and the presence of radioactivity. The components of NIME can be used to support planning for, response to, and recovery from the effects of a nuclear incident. Recognizing that it is a continuous work-in-progress, the current status of the public health and medical preparedness and response for a nuclear incident is provided.

Public Health and Medical Preparedness for a Nuclear Detonation: The Nuclear Incident Medical Enterprise

PubMed Central

Coleman, C. Norman; Sullivan, Julie M.; Bader, Judith L.; Murrain-Hill, Paula; Koerner, John F.; Garrett, Andrew L.; Weinstock, David M.; Case, Cullen; Hrdina, Chad; Adams, Steven A.; Whitcomb, Robert C.; Graeden, Ellie; Shankman, Robert; Lant, Timothy; Maidment, Bert W.; Hatchett, Richard C.

2014-01-01

Resilience and the ability to mitigate the consequences of a nuclear incident are enhanced by (1) effective planning, preparation and training; (2) ongoing interaction, formal exercises, and evaluation among the sectors involved; (3) effective and timely response and communication; and (4) continuous improvements based on new science, technology, experience and ideas. Public health and medical planning require a complex, multi-faceted systematic approach involving federal, state, local, tribal and territorial governments, private sector organizations, academia, industry, international partners, and individual experts and volunteers. The approach developed by the U.S. Department of Health and Human Services Nuclear Incident Medical Enterprise (NIME) is the result of efforts from government and nongovernment experts. It is a “bottom-up” systematic approach built on the available and emerging science that considers physical infrastructure damage, the spectrum of injuries, a scarce resources setting, the need for decision making in the face of a rapidly evolving situation with limited information early on, timely communication and the need for tools and just-in-time information for responders who will likely be unfamiliar with radiation medicine and uncertain and overwhelmed in the face of the large number of casualties and the presence of radioactivity. The components of NIME can be used to support planning for, response to, and recovery from the effects of a nuclear incident. Recognizing that it is a continuous work-in-progress, the current status of the public health and medical preparedness and response for a nuclear incident is provided. PMID:25551496

Gaseous Electron Multiplier (GEM) Detectors

NASA Astrophysics Data System (ADS)

Gnanvo, Kondo

2017-09-01

Gaseous detectors have played a pivotal role as tracking devices in the field of particle physics experiments for the last fifty years. Recent advances in photolithography and micro processing techniques have enabled the transition from Multi Wire Proportional Chambers (MWPCs) and Drift Chambers to a new family of gaseous detectors refer to as Micro Pattern Gaseous Detectors (MPGDs). MPGDs combine the basic gas amplification principle with micro-structure printed circuits to provide detectors with excellent spatial and time resolution, high rate capability, low material budget and high radiation tolerance. Gas Electron Multiplier (GEMs) is a well-established MPGD technology invented by F. Sauli at CERN in 1997 and deployed various high energy physics (HEP) and nuclear NP experiment for tracking systems of current and future NP experiments. GEM detector combines an exceptional high rate capability (1 MHz / mm2) and robustness against harsh radiation environment with excellent position and timing resolution performances. Recent breakthroughs over the past decade have allowed the possibility for large area GEMs, making them cost effective and high-performance detector candidates to play pivotal role in current and future particle physics experiments. After a brief introduction of the basic principle of GEM technology, I will give a brief overview of the GEM detectors used in particle physics experiments over the past decades and especially in the NP community at Thomas Jefferson National Laboratory (JLab) and Brookhaven National Laboratory (BNL). I will follow by a review of state of the art of the new GEM development for the next generation of colliders such as Electron Ion Collider (EIC) or High Luminosity LHC and future Nuclear Physics experiments. I will conclude with a presentation of the CERN-based RD51 collaboration established in 2008 and its major achievements regarding technological developments and applications of MPGDs.

Cloud physics laboratory project science and applications working group

NASA Technical Reports Server (NTRS)

Hung, R. J.

1977-01-01

The conditions of the expansion chamber under zero gravity environment were simulated. The following three branches of fluid mechanics simulation under low gravity environment were accomplished: (1) oscillation of the water droplet which characterizes the nuclear oscillation in nuclear physics, bubble oscillation of two phase flow in chemical engineering, and water drop oscillation in meteorology; (2) rotation of the droplet which characterizes nuclear fission in nuclear physics, formation of binary stars and rotating stars in astrophysics, and breakup of the water droplet in meteorology; and (3) collision and coalescence of the water droplets which characterizes nuclear fusion in nuclear physics and processes of rain formation in meteorology.

Heat transfer enhancement for spent nuclear fuel assembly disposal packages using metallic void fillers: A prevention technique for solidification shrinkage-induced interfacial gaps

NASA Astrophysics Data System (ADS)

Park, Yongsoo; McKrell, Thomas J.; Driscoll, Michael J.

2017-06-01

This study considers replacing the externally accessible void spaces inside a disposal package containing a spent nuclear fuel assembly (SNFA) with high heat conducting metal to increase the effective thermal conductivity of the package and simplify the heat transfer mechanism inside the package by reducing it to a conduction dominant problem. The focus of the study is on preventing the gaps adjacent to the walls of the package components, produced by solidification shrinkage of poured liquid metal. We approached the problem by providing a temporary coating layer on the components to avoid direct build-up of thick metal oxides on their surface to promote metallic bonding at the interfaces under a non-inert environment. Laboratory scale experiments without SNFA were performed with Zn coated low carbon steel canisters and Zamak-3 void filler under two different filling temperature conditions - below and above the melting point of Zn (designated BMP and AMP respectively). Gap formation was successfully prevented in both cases while we confirmed an open gap in a control experiment, which used an uncoated canister. Minor growth of Al-Fe intermetallic phases was observed at the canister/filler interface of the sample produced under the BMP condition while their growth was significant and showed irregularly distributed morphology in the sample produced under the AMP condition, which has a potential to mitigate excessive residual stresses caused by shrinkage prevention. A procedure for the full-scale application was specified based on the results.

Nuclear chemistry. Annual report, 1974

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

Conzett, H.E.; Edelstein, N.M.; Tsang, C.F.

1975-07-01

The 1974 Nuclear Chemistry Annual Report contains information on research in the following areas: nuclear science (nuclear spectroscopy and radioactivity, nuclear reactions and scattering, nuclear theory); chemical and atomic physics (heavy ion-induced atomic reactions, atomic and molecular spectroscopy, photoelectron spectroscopy and hyperfine interactions); physical, inorganic, and analytical chemistry (x-ray crystallography, physical and inorganic chemistry, geochemistry); and instrumentation. Thesis abstracts, 1974 publication titles, and an author index are also included. Papers having a significant amount of information are listed separately by title. (RWR)

AmpC β-lactamases in nosocomial isolates of Klebsiella pneumoniae from India

PubMed Central

Gupta, Varsha; Kumarasamy, Karthikeyan; Gulati, Neelam; Garg, Ritu; Krishnan, Padma; Chander, Jagdish

2012-01-01

Background & objectives: AmpC β-lactamases are clinically significant since these confer resistance to cephalosporins in the oxyimino group, 7-α methoxycephalosporins and are not affected by available β-lactamase inhibitors. In this study we looked for both extended spectrum β-lactamases (ESBL) and AmpC β-lactamases in Klebsiella pneumoniae clinical isolates. Methods: One hundred consecutive, non-duplicate clinical isolates of K. pneumoniae collected over a period of one year (June 2008 - June 2009) were included in the study. An antibiotic susceptibility method was used with 10 antibiotics for Gram-negative infections which helped in screening for ESBL and AmpC β-lactamases and also in confirmation of ESBL production. The detection of AmpC β-lactamases was done based on screening and confirmatory tests. For screening, disc diffusion zones of cefoxitin <18 mm was taken as cefoxitin resistant. All cefoxitin resistant isolates were tested further by AmpC disk test and modified three dimensional test. Multiplex-PCR was performed for screening the presence of plasmid-mediated AmpC genes. Results: Of the 100 isolates of K. pneumoniae studied, 48 were resistant to cefoxitin on screening. AmpC disk test was positive in 32 (32%) isolates. This was also confirmed with modified three dimensional test. Indentation indicating strong AmpC producer was observed in 25 isolates whereas little distortion (weak AmpC) was observed in 7 isolates. ESBL detection was confirmed by a modification of double disk synergy test in 56 isolates. Cefepime was the best cephalosporin in synergy with tazobactam for detecting ESBL production in isolates co-producing AmpC β-lactamases. The subsets of isolates phenotypically AmpC β-lactamase positive were subjected to amplification of six different families of AmpC gene using multiplex PCR. The sequence analysis revealed 12 CMY-2 and eight DHA-1 types. Interpretation & conclusions: Tazobactam was the best β-lactamase inhibitor for detecting ESBL in presence of AmpC β-lactamase as this is a very poor inducer of AmpC gene. Amongst cephalosporins, cefepime was the best cephalosporin in detecting ESBL in presence of AmpC β-lactamase as it is least hydrolyzed by AmpC enzymes. Cefepime-tazobactam combination disk test would be a simple and best method in detection of ESBLs in Enterobacteriaceae co-producing AmpC β-lactamase in the routine diagnostic microbiology laboratories. PMID:22960890

Keynote address: Reinventing fire: Physics + markets = energy solutions

NASA Astrophysics Data System (ADS)

Lovins, Amory B.

2015-03-01

Rocky Mountain Institute's multi-year, 61-author, peer-reviewed Reinventing Fire synthesis showed how the U.S. can realistically run a 2.6× bigger U.S. economy in 2050 with no oil, coal, or nuclear energy, one-third less natural gas, tripled efficiency, and 74% renewable supplies (80% for electricity). This transition, at historically reasonable rates, could be led by business for profit, applying normal rates of return, with some innovative subnational and administrative policies but no Acts of Congress. Excluding carbon emissions and all other externalities, the net present value would be 5 trillion more favorable than business-as-usual, averaging a 14% Internal Rate of Return.

Upgrade of the IGN-14 neutron generator for research on detection of fusion-plasma products

NASA Astrophysics Data System (ADS)

Igielski, Andrzej; Kurowski, Arkadiusz; Janik, Władysław; Gabańska, Barbara; Woźnicka, Urszula

2015-10-01

The fast neutron generator (IGN-14) at the Institute of Nuclear Physics of the Polish Academy of Sciences (IFJ PAN) in Kraków (Poland) is a laboratory multi-purpose experimental device. Neutrons are produced in a beam-target D-D or D-T reactions. A new vacuum chamber installed directly to the end of the ion guide of IGN-14 makes it possible to measure not only neutrons but also alpha particles in the presence of a mixed radiation field of other accompanying reaction products. The new experimental setup allows test detectors dedicated to spectrometric measurements of thermonuclear fusion reaction products.

AmpH, a bifunctional DD-endopeptidase and DD-carboxypeptidase of Escherichia coli.

PubMed

González-Leiza, Silvia M; de Pedro, Miguel A; Ayala, Juan A

2011-12-01

In Escherichia coli, low-molecular-mass penicillin-binding proteins (LMM PBPs) are important for correct cell morphogenesis. These enzymes display DD-carboxypeptidase and/or dd-endopeptidase activities associated with maturation and remodeling of peptidoglycan (PG). AmpH has been classified as an AmpH-type class C LMM PBP, a group closely related to AmpC β-lactamases. AmpH has been associated with PG recycling, although its enzymatic activity remained uncharacterized until now. Construction and purification of His-tagged AmpH from E. coli permitted a detailed study of its enzymatic properties. The N-terminal export signal of AmpH is processed, but the protein remains membrane associated. The PBP nature of AmpH was demonstrated by its ability to bind the β-lactams Bocillin FL (a fluorescent penicillin) and cefmetazole. In vitro assays with AmpH and specific muropeptides demonstrated that AmpH is a bifunctional DD-endopeptidase and DD-carboxypeptidase. Indeed, the enzyme cleaved the cross-linked dimers tetrapentapeptide (D45) and tetratetrapeptide (D44) with efficiencies (k(cat)/K(m)) of 1,200 M(-1) s(-1) and 670 M(-1) s(-1), respectively, and removed the terminal D-alanine from muropeptides with a C-terminal D-Ala-D-Ala dipeptide. Both DD-peptidase activities were inhibited by 40 μM cefmetazole. AmpH also displayed a weak β-lactamase activity for nitrocefin of 1.4 × 10(-3) nmol/μg protein/min, 1/1,000 the rate obtained for AmpC under the same conditions. AmpH was also active on purified sacculi, exhibiting the bifunctional character that was seen with pure muropeptides. The wide substrate spectrum of the DD-peptidase activities associated with AmpH supports a role for this protein in PG remodeling or recycling.

AmpH, a Bifunctional dd-Endopeptidase and dd-Carboxypeptidase of Escherichia coli▿

PubMed Central

González-Leiza, Silvia M.; de Pedro, Miguel A.; Ayala, Juan A.

2011-01-01

In Escherichia coli, low-molecular-mass penicillin-binding proteins (LMM PBPs) are important for correct cell morphogenesis. These enzymes display dd-carboxypeptidase and/or dd-endopeptidase activities associated with maturation and remodeling of peptidoglycan (PG). AmpH has been classified as an AmpH-type class C LMM PBP, a group closely related to AmpC β-lactamases. AmpH has been associated with PG recycling, although its enzymatic activity remained uncharacterized until now. Construction and purification of His-tagged AmpH from E. coli permitted a detailed study of its enzymatic properties. The N-terminal export signal of AmpH is processed, but the protein remains membrane associated. The PBP nature of AmpH was demonstrated by its ability to bind the β-lactams Bocillin FL (a fluorescent penicillin) and cefmetazole. In vitro assays with AmpH and specific muropeptides demonstrated that AmpH is a bifunctional dd–endopeptidase and dd-carboxypeptidase. Indeed, the enzyme cleaved the cross-linked dimers tetrapentapeptide (D45) and tetratetrapeptide (D44) with efficiencies (kcat/Km) of 1,200 M−1 s−1 and 670 M−1 s−1, respectively, and removed the terminal d-alanine from muropeptides with a C-terminal d-Ala-d-Ala dipeptide. Both dd-peptidase activities were inhibited by 40 μM cefmetazole. AmpH also displayed a weak β-lactamase activity for nitrocefin of 1.4 × 10−3 nmol/μg protein/min, 1/1,000 the rate obtained for AmpC under the same conditions. AmpH was also active on purified sacculi, exhibiting the bifunctional character that was seen with pure muropeptides. The wide substrate spectrum of the dd-peptidase activities associated with AmpH supports a role for this protein in PG remodeling or recycling. PMID:22001512

Nuclear War and Science Teaching.

ERIC Educational Resources Information Center

Hobson, Art

1983-01-01

Suggests that science-related material on nuclear war be included in introductory courses. Lists nuclear war topics for physics, psychology, sociology, biology/ecology, chemistry, geography, geology/meteorology, mathematics, and medical science. Also lists 11 lectures on nuclear physics which include nuclear war topics. (JN)

Discovery of a cAMP Deaminase That Quenches Cyclic AMP-Dependent Regulation

PubMed Central

Goble, Alissa M.; Feng, Youjun; Raushel, Frank M.; Cronan, John E.

2013-01-01

An enzyme of unknown function within the amidohydrolase superfamily was discovered to catalyze the hydrolysis of the universal second messenger, cyclic-3’, 5’-adenosine monophosphate (cAMP). The enzyme, which we have named CadD, is encoded by the human pathogenic bacterium Leptospira interrogans. Although CadD is annotated as an adenosine deaminase, the protein specifically deaminates cAMP to cyclic-3’, 5’-inosine monophosphate (cIMP) with a kcat/Km of 2.7 ± 0.4 × 105 M−1 s−1 and has no activity on adenosine, adenine, or 5’-adenosine monophosphate (AMP). This is the first identification of a deaminase specific for cAMP. Expression of CadD in Escherichia coli mimics the loss of adenylate cyclase in that it blocks growth on carbon sources that require the cAMP-CRP transcriptional activator complex for expression of the cognate genes. The cIMP reaction product cannot replace cAMP as the ligand for CRP binding to DNA in vitro and cIMP is a very poor competitor of cAMP activation of CRP for DNA binding. Transcriptional analyses indicate that CadD expression represses expression of several cAMP-CRP dependent genes. CadD adds a new activity to the cAMP metabolic network and may be a useful tool in intracellular study of cAMP-dependent processes. PMID:24074367

Expression profiles of antimicrobial peptides (AMPs) and their regulation by Relish

NASA Astrophysics Data System (ADS)

Wang, Dongdong; Li, Fuhua; Li, Shihao; Wen, Rong; Xiang, Jianhai

2012-07-01

Antimicrobial peptides (AMPs), as key immune effectors, play important roles in the innate immune system of invertebrates. Different types of AMPs, including Penaeidin, Crustin, ALF (antilipopolysaccharide factor) have been identified in different penaeid shrimp; however, systematic analyses on the function of different AMPs in shrimp responsive to different types of bacteria are very limited. In this study, we analyzed the expression profiles of AMPs in the Chinese shrimps, Fenneropenaeus chinensis, simultaneously by real-time RT-PCR (reverse transcription-polymerase chain reaction) when shrimp were challenged with Micrococcus lysodeikticus (Gram-positive, G+) or Vibrio anguillarium (Gram-negative, G-). Different AMPs showed different expression profiles when shrimp were injected with one type of bacterium, and one AMP also showed different expression profiles when shrimp were challenged with different bacteria. Furthermore, the expression of these AMPs showed temporal expression profiles, suggesting that different AMPs function coordinately in bacteria-infected shrimp. An RNA interference approach was used to study the function of the Relish transcription factor in regulating the transcription of different AMPs. The current study showed that Relish could regulate the transcription of different AMPs in shrimp. Differential expression profiles of AMPs in shrimp injected with different types of bacteria indicated that a complicated antimicrobial response network existed in shrimp. These data contribute to our understanding of immunity in shrimp and may provide a strategy for the control of disease in shrimp.

Cyclic AMP Inhibits the Activity and Promotes the Acetylation of Acetyl-CoA Synthetase through Competitive Binding to the ATP/AMP Pocket.

PubMed

Han, Xiaobiao; Shen, Liqiang; Wang, Qijun; Cen, Xufeng; Wang, Jin; Wu, Meng; Li, Peng; Zhao, Wei; Zhang, Yu; Zhao, Guoping

2017-01-27

The high-affinity biosynthetic pathway for converting acetate to acetyl-coenzyme A (acetyl-CoA) is catalyzed by the central metabolic enzyme acetyl-coenzyme A synthetase (Acs), which is finely regulated both at the transcriptional level via cyclic AMP (cAMP)-driven trans-activation and at the post-translational level via acetylation inhibition. In this study, we discovered that cAMP directly binds to Salmonella enterica Acs (SeAcs) and inhibits its activity in a substrate-competitive manner. In addition, cAMP binding increases SeAcs acetylation by simultaneously promoting Pat-dependent acetylation and inhibiting CobB-dependent deacetylation, resulting in enhanced SeAcs inhibition. A crystal structure study and site-directed mutagenesis analyses confirmed that cAMP binds to the ATP/AMP pocket of SeAcs, and restrains SeAcs in an open conformation. The cAMP contact residues are well conserved from prokaryotes to eukaryotes, suggesting a general regulatory mechanism of cAMP on Acs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

cAMP enhances BMP2-signaling through PKA and MKP1-dependent mechanisms

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

Ghayor, Chafik; Ehrbar, Martin; Miguel, Blanca San

2009-04-03

Recent studies suggest that the elevation of intracellular cyclic adenosine monophosphate (cAMP) and the activation of the protein kinase A regulate BMP-induced osteogenesis. However, the precise mechanisms underlying the enhancing effect of cAMP on BMP2 signaling were not completely revealed. In this study we investigated the effect of elevated cAMP level and PKA activation on the BMP2-induced osteoblastic differentiation in pluripotent C2C12 cells. Alkaline phosphatase activity and its mRNA were consistently induced by BMP2 treatment. The pretreatment of C2C12 cells with Forskolin, a cAMP generating agent, dbcAMP, an analogue of cAMP, or IBMX (3-isobutyl 1-methyl xanthine), and a nonspecific inhibitormore » of phosphodiesterases elicited further activation of alkaline phosphatase. Furthermore, elevated intracellular cAMP level increased BMP2-induced MKP1. On the other hand, BMP2-induced Erk phosphorylation (p44/p42) and cell proliferation were suppressed in the presence of cAMP. Thus, cAMP might enhance BMP2-induced osteoblastic differentiation by a MKP1-Erk-dependent mechanism.« less

cAMP dependent and independent regulation of thyroglobulin synthesis by two clones of the OVNIS 6H thyroid cell line.

PubMed

Aouani, A; Hovsépian, S; Fayet, G

1987-07-01

The hormonal regulation of thyroglobulin synthesis has been studied using two independent clones of the OVNIS 6H cell line. Insulin, hydrocortisone and TSH were able to stimulate thyroglobulin synthesis, whereas transferrin, somatostatin and glycyl-histidyl-lysine were without effect. Insulin stimulated thyroglobulin synthesis without affecting cAMP production. Hydrocortisone, when combined with insulin was a stimulator too; this stimulation was not accompanied by an increase in cAMP. TSH alone was unable to stimulate either cAMP or thyroglobulin synthesis. The stimulatory effect of TSH on thyroglobulin synthesis took place only when combined with insulin or insulin plus hydrocortisone, and was mediated by cAMP. Consequently, insulin and hydrocortisone stimulated thyroglobulin synthesis by cAMP-independent mechanisms, whereas TSH acted via the cAMP system. Forskolin mimicked TSH effects on cAMP and thyroglobulin synthesis. Calf serum inhibited cAMP and thyroglobulin production. Optimal cAMP and thyroglobulin synthesis as well as TSH responsiveness were obtained in serum-free medium supplemented with 5 micrograms/ml insulin, 100 nM hydrocortisone and 1 mU/ml TSH.

Mechanisms Restricting Diffusion of Intracellular cAMP.

PubMed

Agarwal, Shailesh R; Clancy, Colleen E; Harvey, Robert D

2016-01-22

Although numerous receptors stimulate cAMP production in a wide array of cells, many elicit distinct, highly localized responses, implying that the subcellular distribution of cAMP is not uniform. One often used explanation is that phosphodiesterases, which breakdown cAMP, act as functional barriers limiting diffusion. However, several studies refute the notion that this is sufficient, suggesting that phosphodiesterase-independent movement of cAMP must occur at rates slower than free diffusion. But, until now this has never been demonstrated. Using Raster Image Correlation Spectroscopy (RICS), we measured the diffusion coefficient of a fluorescently-labeled cAMP derivative (φ450-cAMP) as well as other fluorescent molecules in order to investigate the role that molecular size, cell morphology, and buffering by protein kinase A (PKA) play in restricting cAMP mobility in different cell types. Our results demonstrate that cytosolic movement of cAMP is indeed much slower than the rate of free diffusion and that interactions with PKA, especially type II PKA associated with mitochondria, play a significant role. These findings have important implications with respect to cAMP signaling in all cells.

Mechanisms Restricting Diffusion of Intracellular cAMP

PubMed Central

Agarwal, Shailesh R.; Clancy, Colleen E.; Harvey, Robert D.

2016-01-01

Although numerous receptors stimulate cAMP production in a wide array of cells, many elicit distinct, highly localized responses, implying that the subcellular distribution of cAMP is not uniform. One often used explanation is that phosphodiesterases, which breakdown cAMP, act as functional barriers limiting diffusion. However, several studies refute the notion that this is sufficient, suggesting that phosphodiesterase-independent movement of cAMP must occur at rates slower than free diffusion. But, until now this has never been demonstrated. Using Raster Image Correlation Spectroscopy (RICS), we measured the diffusion coefficient of a fluorescently-labeled cAMP derivative (φ450-cAMP) as well as other fluorescent molecules in order to investigate the role that molecular size, cell morphology, and buffering by protein kinase A (PKA) play in restricting cAMP mobility in different cell types. Our results demonstrate that cytosolic movement of cAMP is indeed much slower than the rate of free diffusion and that interactions with PKA, especially type II PKA associated with mitochondria, play a significant role. These findings have important implications with respect to cAMP signaling in all cells. PMID:26795432

Multi-reactor power system configurations for multimegawatt nuclear electric propulsion

NASA Technical Reports Server (NTRS)

George, Jeffrey A.

1991-01-01

A modular, multi-reactor power system and vehicle configuration for piloted nuclear electric propulsion (NEP) missions to Mars is presented. Such a design could provide enhanced system and mission reliability, allowing a comfortable safety margin for early manned flights, and would allow a range of piloted and cargo missions to be performed with a single power system design. Early use of common power modules for cargo missions would also provide progressive flight experience and validation of standardized systems for use in later piloted applications. System and mission analysis are presented to compare single and multi-reactor configurations for piloted Mars missions. A conceptual design for the Hydra modular multi-reactor NEP vehicle is presented.

Nuclear security and radiological preparedness for the olympic games, athens 2004: lessons learned for organizing major public events.

PubMed

Kamenopoulou, Vassiliki; Dimitriou, Panayiotis; Hourdakis, Constantine J; Maltezos, Antonios; Matikas, Theodore; Potiriadis, Constantinos; Camarinopoulos, Leonidas

2006-10-01

In light of the exceptional circumstances that arose from hosting the Olympic Games in Athens in 2004 and from recent terrorist events internationally, Greece attributes the highest priority to security issues. According to its statutory role, the Greek Atomic Energy Commission is responsible for emergency preparedness and response in case of nuclear and radiological events, and advises the Government on the measures and interventions necessary to protect the public. In this context, the Commission participated in the Nuclear, Radiological, Biological, and Chemical Threat National Emergency Plan, specially developed for the Olympic Games, and coordinated by the Olympic Games Security Division. The objective of this paper is to share the experience gained during the organization of the Olympic Games and to present the nuclear security program implemented prior to, during, and beyond the Games, in order to prevent, detect, assess, and respond to the threat of nuclear terrorism. This program adopted a multi-area coverage of nuclear security, including physical protection of nuclear and radiological facilities, prevention of smuggling of radioactive materials through borders, prevention of dispersion of these materials into the Olympic venues, enhancement of emergency preparedness and response to radiological events, upgrading of the technical infrastructure, establishment of new procedures for assessing the threat and responding to radiological incidents, and training personnel belonging to several organizations involved in the National Emergency Response Plan. Finally, the close cooperation of Greek Authorities with the International Atomic Energy Agency and the U.S. Department of Energy, under the coordination of the Greek Atomic Energy Commission, is also discussed.

Optimization of coupled multiphysics methodology for safety analysis of pebble bed modular reactor

NASA Astrophysics Data System (ADS)

Mkhabela, Peter Tshepo

The research conducted within the framework of this PhD thesis is devoted to the high-fidelity multi-physics (based on neutronics/thermal-hydraulics coupling) analysis of Pebble Bed Modular Reactor (PBMR), which is a High Temperature Reactor (HTR). The Next Generation Nuclear Plant (NGNP) will be a HTR design. The core design and safety analysis methods are considerably less developed and mature for HTR analysis than those currently used for Light Water Reactors (LWRs). Compared to LWRs, the HTR transient analysis is more demanding since it requires proper treatment of both slower and much longer transients (of time scale in hours and days) and fast and short transients (of time scale in minutes and seconds). There is limited operation and experimental data available for HTRs for validation of coupled multi-physics methodologies. This PhD work developed and verified reliable high fidelity coupled multi-physics models subsequently implemented in robust, efficient, and accurate computational tools to analyse the neutronics and thermal-hydraulic behaviour for design optimization and safety evaluation of PBMR concept The study provided a contribution to a greater accuracy of neutronics calculations by including the feedback from thermal hydraulics driven temperature calculation and various multi-physics effects that can influence it. Consideration of the feedback due to the influence of leakage was taken into account by development and implementation of improved buckling feedback models. Modifications were made in the calculation procedure to ensure that the xenon depletion models were accurate for proper interpolation from cross section tables. To achieve this, the NEM/THERMIX coupled code system was developed to create the system that is efficient and stable over the duration of transient calculations that last over several tens of hours. Another achievement of the PhD thesis was development and demonstration of full-physics, three-dimensional safety analysis methodology for the PBMR to provide reference solutions. Investigation of different aspects of the coupled methodology and development of efficient kinetics treatment for the PBMR were carried out, which accounts for all feedback phenomena in an efficient manner. The OECD/NEA PBMR-400 coupled code benchmark was used as a test matrix for the proposed investigations. The integrated thermal-hydraulics and neutronics (multi-physics) methods were extended to enable modeling of a wider range of transients pertinent to the PBMR. First, the effect of the spatial mapping schemes (spatial coupling) was studied and quantified for different types of transients, which resulted in implementation of improved mapping methodology based on user defined criteria. The second aspect that was studied and optimized is the temporal coupling and meshing schemes between the neutronics and thermal-hydraulics time step selection algorithms. The coupled code convergence was achieved supplemented by application of methods to accelerate it. Finally, the modeling of all feedback phenomena in PBMRs was investigated and a novel treatment of cross-section dependencies was introduced for improving the representation of cross-section variations. The added benefit was that in the process of studying and improving the coupled multi-physics methodology more insight was gained into the physics and dynamics of PBMR, which will help also to optimize the PBMR design and improve its safety. One unique contribution of the PhD research is the investigation of the importance of the correct representation of the three-dimensional (3-D) effects in the PBMR analysis. The performed studies demonstrated that explicit 3-D modeling of control rod movement is superior and removes the errors associated with the grey curtain (2-D homogenized) approximation.

AMP Affects Intracellular Ca2+ Signaling, Migration, Cytokine Secretion and T Cell Priming Capacity of Dendritic Cells

PubMed Central

Panther, Elisabeth; Dürk, Thorsten; Ferrari, Davide; Di Virgilio, Francesco; Grimm, Melanie; Sorichter, Stephan; Cicko, Sanja; Herouy, Yared; Norgauer, Johannes; Idzko, Marco; Müller, Tobias

2012-01-01

The nucleotide adenosine-5′-monophosphate (AMP) can be released by various cell types and has been shown to elicit different cellular responses. In the extracellular space AMP is dephosphorylated to the nucleoside adenosine which can then bind to adenosine receptors. However, it has been shown that AMP can also activate A1 and A2a receptors directly. Here we show that AMP is a potent modulator of mouse and human dendritic cell (DC) function. AMP increased intracellular Ca2+ concentration in a time and dose dependent manner. Furthermore, AMP stimulated actin-polymerization in human DCs and induced migration of immature human and bone marrow derived mouse DCs, both via direct activation of A1 receptors. AMP strongly inhibited secretion of TNF-α and IL-12p70, while it enhanced production of IL-10 both via activation of A2a receptors. Consequently, DCs matured in the presence of AMP and co-cultivated with naive CD4+CD45RA+ T cells inhibited IFN-γ production whereas secretion of IL-5 and IL-13 was up-regulated. An enhancement of Th2-driven immune response could also be observed when OVA-pulsed murine DCs were pretreated with AMP prior to co-culture with OVA-transgenic naïve OTII T cells. An effect due to the enzymatic degradation of AMP to adenosine could be ruled out, as AMP still elicited migration and changes in cytokine secretion in bone-marrow derived DCs generated from CD73-deficient animals and in human DCs pretreated with the ecto-nucleotidase inhibitor 5′-(alpha,beta-methylene) diphosphate (APCP). Finally, the influence of contaminating adenosine could be excluded, as AMP admixed with adenosine desaminase (ADA) was still able to influence DC function. In summary our data show that AMP when present during maturation is a potent regulator of dendritic cell function and point out the role for AMP in the pathogenesis of inflammatory disorders. PMID:22624049

c-di-AMP: An Essential Molecule in the Signaling Pathways that Regulate the Viability and Virulence of Gram-Positive Bacteria

PubMed Central

Fahmi, Tazin; Port, Gary C.

2017-01-01

Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key roles in many signal transduction pathways used by prokaryotes and/or eukaryotes. Among the various second messenger nucleotides molecules, c-di-AMP was discovered recently and has since been shown to be involved in cell growth, survival, and regulation of virulence, primarily within Gram-positive bacteria. The cellular level of c-di-AMP is maintained by a family of c-di-AMP synthesizing enzymes, diadenylate cyclases (DACs), and degradation enzymes, phosphodiesterases (PDEs). Genetic manipulation of DACs and PDEs have demonstrated that alteration of c-di-AMP levels impacts both growth and virulence of microorganisms. Unlike other second messenger molecules, c-di-AMP is essential for growth in several bacterial species as many basic cellular functions are regulated by c-di-AMP including cell wall maintenance, potassium ion homeostasis, DNA damage repair, etc. c-di-AMP follows a typical second messenger signaling pathway, beginning with binding to receptor molecules to subsequent regulation of downstream cellular processes. While c-di-AMP binds to specific proteins that regulate pathways in bacterial cells, c-di-AMP also binds to regulatory RNA molecules that control potassium ion channel expression in Bacillus subtilis. c-di-AMP signaling also occurs in eukaryotes, as bacterially produced c-di-AMP stimulates host immune responses during infection through binding of innate immune surveillance proteins. Due to its existence in diverse microorganisms, its involvement in crucial cellular activities, and its stimulating activity in host immune responses, c-di-AMP signaling pathway has become an attractive antimicrobial drug target and therefore has been the focus of intensive study in several important pathogens. PMID:28783096

cAMP-secretion coupling is impaired in diabetic GK/Par rat β-cells: a defect counteracted by GLP-1.

PubMed

Dolz, Manuel; Movassat, Jamileh; Bailbé, Danielle; Le Stunff, Hervé; Giroix, Marie-Hélène; Fradet, Magali; Kergoat, Micheline; Portha, Bernard

2011-11-01

cAMP-raising agents with glucagon-like peptide-1 (GLP-1) as the first in class, exhibit multiple actions that are beneficial for the treatment of type 2 diabetic (T2D) patients, including improvement of glucose-induced insulin secretion (GIIS). To gain additional insight into the role of cAMP in the disturbed stimulus-secretion coupling within the diabetic β-cell, we examined more thoroughly the relationship between changes in islet cAMP concentration and insulin release in the GK/Par rat model of T2D. Basal cAMP content in GK/Par islets was significantly higher, whereas their basal insulin release was not significantly different from that of Wistar (W) islets. Even in the presence of IBMX or GLP-1, their insulin release did not significantly change despite further enhanced cAMP accumulation in both cases. The high basal cAMP level most likely reflects an increased cAMP generation in GK/Par compared with W islets since 1) forskolin dose-dependently induced an exaggerated cAMP accumulation; 2) adenylyl cyclase (AC)2, AC3, and G(s)α proteins were overexpressed; 3) IBMX-activated cAMP accumulation was less efficient and PDE-3B and PDE-1C mRNA were decreased. Moreover, the GK/Par insulin release apparatus appears less sensitive to cAMP, since GK/Par islets released less insulin at submaximal cAMP levels and required five times more cAMP to reach a maximal secretion rate no longer different from W. GLP-1 was able to reactivate GK/Par insulin secretion so that GIIS became indistinguishable from that of W. The exaggerated cAMP production is instrumental, since GLP-1-induced GIIS reactivation was lost in the presence the AC blocker 2',5'-dideoxyadenosine. This GLP-1 effect takes place in the absence of any improvement of the [Ca(2+)](i) response and correlates with activation of the cAMP-dependent PKA-dependent pathway.

8-Bromo-cAMP decreases the Ca2+ sensitivity of airway smooth muscle contraction through a mechanism distinct from inhibition of Rho-kinase.

PubMed

Endou, Katsuaki; Iizuka, Kunihiko; Yoshii, Akihiro; Tsukagoshi, Hideo; Ishizuka, Tamotsu; Dobashi, Kunio; Nakazawa, Tsugio; Mori, Masatomo

2004-10-01

To clarify whether cyclic AMP (cAMP)/cAMP-dependent protein kinase (PKA) activation and Rho-kinase inhibition share a common mechanism to decrease the Ca2+ sensitivity of airway smooth muscle contraction, we examined the effects of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), a stable cAMP analog, and (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide dihydrochloride, monohydrate (Y-27632), a Rho-kinase inhibitor, on carbachol (CCh)-, guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS)-, 4beta-phorbol 12,13-dibutyrate (PDBu)-, and leukotriene D4 (LTD4)-induced Ca2+ sensitization in alpha-toxin-permeabilized rabbit tracheal and human bronchial smooth muscle. In rabbit trachea, CCh-induced smooth muscle contraction was inhibited by 8-BrcAMP and Y-27632 to a similar extent. However, GTPgammaS-induced smooth muscle contraction was resistant to 8-BrcAMP. In the presence of a saturating concentration of Y-27632, PDBu-induced smooth muscle contraction was completely reversed by 8-BrcAMP. Conversely, PDBu-induced smooth muscle contraction was resistant to Y-27632. In the presence of a saturating concentration of 8-BrcAMP, GTPgammaS-induced Ca2+ sensitization was also reversed by Y-27632. The 8-BrcAMP had no effect on the ATP-triggered contraction of tracheal smooth muscle that had been treated with calyculin A in rigor solutions. The 8-BrcAMP and Y-27632 additively accelerated the relaxation rate of PDBu- and GTPgammaS-treated smooth muscle under myosin light chain kinase-inhibited conditions. In human bronchus, LTD4-induced smooth muscle contraction was inhibited by both 8-BrcAMP and Y-27632. We conclude that cAMP/PKA-induced Ca2+ desensitization contains at least two mechanisms: 1) inhibition of the muscarinic receptor signaling upstream from Rho activation and 2) cAMP/PKA's preferential reversal of PKC-mediated Ca2+ sensitization in airway smooth muscle.

Enzymatic Characterization of AMP Phosphorylase and Ribose-1,5-Bisphosphate Isomerase Functioning in an Archaeal AMP Metabolic Pathway

PubMed Central

Aono, Riku; Sato, Takaaki; Yano, Ayumu; Yoshida, Shosuke; Nishitani, Yuichi; Miki, Kunio; Imanaka, Tadayuki

2012-01-01

AMP phosphorylase (AMPpase), ribose-1,5-bisphosphate (R15P) isomerase, and type III ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) have been proposed to constitute a novel pathway involved in AMP metabolism in the Archaea. Here we performed a biochemical examination of AMPpase and R15P isomerase from Thermococcus kodakarensis. R15P isomerase was specific for the α-anomer of R15P and did not recognize other sugar compounds. We observed that activity was extremely low with the substrate R15P alone but was dramatically activated in the presence of AMP. Using AMP-activated R15P isomerase, we reevaluated the substrate specificity of AMPpase. AMPpase exhibited phosphorylase activity toward CMP and UMP in addition to AMP. The [S]-v plot (plot of velocity versus substrate concentration) of the enzyme toward AMP was sigmoidal, with an increase in activity observed at concentrations higher than approximately 3 mM. The behavior of the two enzymes toward AMP indicates that the pathway is intrinsically designed to prevent excess degradation of intracellular AMP. We further examined the formation of 3-phosphoglycerate from AMP, CMP, and UMP in T. kodakarensis cell extracts. 3-Phosphoglycerate generation was observed from AMP alone, and from CMP or UMP in the presence of dAMP, which also activates R15P isomerase. 3-Phosphoglycerate was not formed when 2-carboxyarabinitol 1,5-bisphosphate, a Rubisco inhibitor, was added. The results strongly suggest that these enzymes are actually involved in the conversion of nucleoside monophosphates to 3-phosphoglycerate in T. kodakarensis. PMID:23065974

Physical and Mechanical Metallurgy of Zirconium Alloys for Nuclear Applications: A Multi-Scale Computational Study

NASA Astrophysics Data System (ADS)

Glazoff, Michael Vasily

In the post-Fukushima world, thermal and structural stability of materials under extreme conditions is an important issue for the safety of nuclear reactors. Because the nuclear industry will continue using zirconium (Zr) cladding for the foreseeable future, it becomes critical to gain a fundamental understanding of several interconnected problems. First, what are the thermodynamic and kinetic factors affecting oxidation and hydrogen pick-up by these materials at normal, off-normal conditions, and in long-term storage? Secondly, what protective coatings could be used in order to gain valuable time at off-normal conditions (temperature exceeds ~1200°C (2200°F)? Thirdly, the kinetics of the coating's oxidation must be understood. Lastly, one needs automated inspection algorithms allowing identifying cladding's defects. This work attempts to explore the problem from a computational perspective, utilizing first principles atomistic simulations, computational thermodynamics, plasticity theory, and morphological algorithms of image processing for defect identification. It consists of the four parts dealing with these four problem areas preceded by the introduction. In the 1st part, computational thermodynamics and ab initio calculations were used to shed light upon the different stages of zircaloy oxidation and hydrogen pickup, and microstructure optimization to increase thermal stability. The 2 nd part describes the kinetic theory of oxidation of the several materials considered to be perspective coatings for Zr alloys: SiC and ZrSiO4. The 3rd part deals with understanding the respective roles of the two different plasticity mechanisms in Zr nuclear alloys: twinning (at low T) and crystallographic slip (higher T's). For that goal, an advanced plasticity model was proposed. In the 4th part projectional algorithms for defect identification in zircaloy coatings are described. Conclusions and recommendations are presented in the 5th part. This integrative approach's value is in developing multi-faceted understanding of complex processes taking place in nuclear fuel rods. It helped identify several problems pertaining to the safe operations with nuclear fuel: limits of temperature that should be strictly obeyed in storage to retard zircaloy hydriding; understanding the benefits and limitations of coatings; developing in-depth understanding of Zr plasticity; developing original algorithms for defect identification in SiC-braided zircaloy. The obtained results will be useful for the nuclear industry.

Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice

PubMed Central

Froese, Alexander; Breher, Stephanie S.; Waldeyer, Christoph; Schindler, Roland F.R.; Nikolaev, Viacheslav O.; Rinné, Susanne; Wischmeyer, Erhard; Schlueter, Jan; Becher, Jan; Simrick, Subreena; Vauti, Franz; Kuhtz, Juliane; Meister, Patrick; Kreissl, Sonja; Torlopp, Angela; Liebig, Sonja K.; Laakmann, Sandra; Müller, Thomas D.; Neumann, Joachim; Stieber, Juliane; Ludwig, Andreas; Maier, Sebastian K.; Decher, Niels; Arnold, Hans-Henning; Kirchhof, Paulus; Fabritz, Larissa; Brand, Thomas

2012-01-01

Cardiac pacemaker cells create rhythmic pulses that control heart rate; pacemaker dysfunction is a prevalent disorder in the elderly, but little is known about the underlying molecular causes. Popeye domain containing (Popdc) genes encode membrane proteins with high expression levels in cardiac myocytes and specifically in the cardiac pacemaking and conduction system. Here, we report the phenotypic analysis of mice deficient in Popdc1 or Popdc2. ECG analysis revealed severe sinus node dysfunction when freely roaming mutant animals were subjected to physical or mental stress. In both mutants, bradyarrhythmia developed in an age-dependent manner. Furthermore, we found that the conserved Popeye domain functioned as a high-affinity cAMP-binding site. Popdc proteins interacted with the potassium channel TREK-1, which led to increased cell surface expression and enhanced current density, both of which were negatively modulated by cAMP. These data indicate that Popdc proteins have an important regulatory function in heart rate dynamics that is mediated, at least in part, through cAMP binding. Mice with mutant Popdc1 and Popdc2 alleles are therefore useful models for the dissection of the mechanisms causing pacemaker dysfunction and could aid in the development of strategies for therapeutic intervention. PMID:22354168

Control of the Flow Properties of DNA by Topoisomerase II and Its Targeting Inhibitor

PubMed Central

Kundukad, Binu; van der Maarel, Johan R.C.

2010-01-01

The flow properties of DNA are important for understanding cell division and, indirectly, cancer therapy. DNA topology controlling enzymes such as topoisomerase II are thought to play an essential role. We report experiments showing how double-strand passage facilitated by topoisomerase II controls DNA rheology. For this purpose, we have measured the elastic storage and viscous loss moduli of a model system comprising bacteriophage λ-DNA and human topoisomerase IIα using video tracking of the Brownian motion of colloidal probe particles. We found that the rheology is critically dependent on the formation of temporal entanglements among the DNA molecules with a relaxation time of ∼1 s. We observed that topoisomerase II effectively removes these entanglements and transforms the solution from an elastic physical gel to a viscous fluid depending on the consumption of ATP. A second aspect of this study is the effect of the generic topoisomerase II inhibitor adenylyl-imidodiphosphate (AMP-PNP). In mixtures of AMP-PNP and ATP, the double-strand passage reaction gets blocked and progressively fewer entanglements are relaxed. A total replacement of ATP by AMP-PNP results in a temporal increase in elasticity at higher frequencies, but no transition to an elastic gel with fixed cross-links. PMID:20858436

Anticonvulsant effect of AMP by direct activation of adenosine A1 receptor.

PubMed

Muzzi, Mirko; Coppi, Elisabetta; Pugliese, Anna Maria; Chiarugi, Alberto

2013-12-01

Purinergic neurotransmission mediated by adenosine (Ado) type 1 receptors (A1Rs) plays pivotal roles in negative modulation of epileptic seizures, and Ado is thought to be a key endogenous anticonvulsant. Recent evidence, however, indicates that AMP, the metabolic precursor of Ado, also activate A1Rs. Here, we evaluated the antiepileptic effects of AMP adopting in vitro and in vivo models of epilepsy. We report that AMP reversed the increase in population spike (PS) amplitude and the decrease in PS latency induced by a Mg(2+)-free extracellular solution in CA1 neurons of mouse hippocampal slices. The AMP effects were inhibited by the A1R antagonist DPCPX, but not prevented by inhibiting conversion of AMP into Ado, indicating that AMP inhibited per se sustained hippocampal excitatory neurotransmission by directly activating A1Rs. AMP also reduced seizure severity and mortality in a model of audiogenic convulsion. Of note, the anticonvulsant effects of AMP were potentiated by preventing its conversion into Ado and inhibited by DPCPX. When tested in a model of kainate-induced seizure, AMP prolonged latency of convulsions but had no effects on seizure severity and mortality. Data provide the first evidence that AMP is an endogenous anticonvulsant acting at A1Rs. © 2013.

The relationship between pulsatile GnRH secretion and cAMP production in immortalized GnRH neurons.

PubMed

Frattarelli, John L; Krsmanovic, Lazar Z; Catt, Kevin J

2011-06-01

In perifused immortalized GnRH neurons (GT1-7), simultaneous measurements of GnRH and cAMP revealed that the secretory profiles for both GnRH and cAMP are pulsatile. An analysis of GnRH and cAMP pulses in 16 independent experiments revealed that 25% of pulses coincide. Inversion of the peak and nadir levels was found in 33% and random relationship between GnRH and cAMP found in 42% of analyzed pulses. The random relation between GnRH and cAMP pulse resets to synchronous after an inverse relation between pulses occurred during the major GnRH release, indicating that GnRH acts as a switching mechanism to synchronize cAMP and GnRH release in perifused GT1-7 neurons. Activation of GnRH receptors with increasing agonist concentrations caused a biphasic change in cAMP levels. Low nanomolar concentrations increased cAMP production, but at high concentrations the initial increase was followed by a rapid decline to below the basal level. Blockade of the GnRH receptors by peptide and nonpeptide antagonists generated monotonic nonpulsatile increases in both GnRH and cAMP production. These findings indicate that cAMP positively regulates GnRH secretion but does not participate in the mechanism of pulsatile GnRH release.

Exchange protein activated by cAMP (Epac) mediates cAMP-dependent but protein kinase A-insensitive modulation of vascular ATP-sensitive potassium channels

PubMed Central

Purves, Gregor I; Kamishima, Tomoko; Davies, Lowri M; Quayle, John M; Dart, Caroline

2009-01-01

Exchange proteins directly activated by cyclic AMP (Epacs or cAMP-GEF) represent a family of novel cAMP-binding effector proteins. The identification of Epacs and the recent development of pharmacological tools that discriminate between cAMP-mediated pathways have revealed previously unrecognized roles for cAMP that are independent of its traditional target cAMP-dependent protein kinase (PKA). Here we show that Epac exists in a complex with vascular ATP-sensitive potassium (KATP) channel subunits and that cAMP-mediated activation of Epac modulates KATP channel activity via a Ca2+-dependent mechanism involving the activation of Ca2+-sensitive protein phosphatase 2B (PP-2B, calcineurin). Application of the Epac-specific cAMP analogue 8-pCPT-2′-O-Me-cAMP, at concentrations that activate Epac but not PKA, caused a 41.6 ± 4.7% inhibition (mean ±s.e.m.; n= 7) of pinacidil-evoked whole-cell KATP currents recorded in isolated rat aortic smooth muscle cells. Importantly, similar results were obtained when cAMP was elevated by addition of the adenylyl cyclase activator forskolin in the presence of the structurally distinct PKA inhibitors, Rp-cAMPS or KT5720. Activation of Epac by 8-pCPT-2′-O-Me-cAMP caused a transient 171.0 ± 18.0 nm (n= 5) increase in intracellular Ca2+ in Fura-2-loaded aortic myocytes, which persisted in the absence of extracellular Ca2+. Inclusion of the Ca2+-specific chelator BAPTA in the pipette-filling solution or preincubation with the calcineurin inhibitors, cyclosporin A or ascomycin, significantly reduced the ability of 8-pCPT-2′-O-Me-cAMP to inhibit whole-cell KATP currents. These results highlight a previously undescribed cAMP-dependent regulatory mechanism that may be essential for understanding the physiological and pathophysiological roles ascribed to arterial KATP channels in the control of vascular tone and blood flow. PMID:19491242

Science with radioactive beams: the alchemist's dream

NASA Astrophysics Data System (ADS)

Gelletly, W.

2001-05-01

Nuclear science is being transformed by a new capacity to create beams of radioactive nuclei. Until now all of our knowledge of nuclear physics and the applications which flow from it has been derived from studies of radioactive decay and nuclear reactions induced by beams of the 283 stable or long-lived nuclear species we can find on Earth. Here we describe first how beams of radioactive nuclei can be created. The present status of nuclear physics is then reviewed before potential applications to nuclear physics, nuclear astrophysics, materials science, bio-medical, and environmental studies are described.

Experiment definition studies for AMPS Spacelab

NASA Technical Reports Server (NTRS)

Liemohn, H.

1975-01-01

The electrical charging of the space shuttle orbiter is discussed in relation to the AMPS Spacelab payload along with an operations research technique for the selection of AMPS Spacelab experiments. Experiments proposed for AMPS include: hydromagnetic wave experiments; bistatic sounder of AMPS wake; and an artificial meteor gun. Experiment objectives and instrument functions are given for all experiments.

Cannabinoid inhibition of adenylate cyclase-mediated signal transduction and interleukin 2 (IL-2) expression in the murine T-cell line, EL4.IL-2.

PubMed

Condie, R; Herring, A; Koh, W S; Lee, M; Kaminski, N E

1996-05-31

Cannabinoid receptors negatively regulate adenylate cyclase through a pertussis toxin-sensitive GTP-binding protein. In the present studies, signaling via the adenylate cyclase/cAMP pathway was investigated in the murine thymoma-derived T-cell line, EL4.IL-2. Northern analysis of EL4.IL-2 cells identified the presence of 4-kilobase CB2 but not CB1 receptor-subtype mRNA transcripts. Southern analysis of genomic DNA digests for the CB2 receptor demonstrated identical banding patterns for EL4.IL-2 cells and mouse-derived DNA, both of which were dissimilar to DNA isolated from rat. Treatment of EL4.IL-2 cells with either cannabinol or Delta9-THC disrupted the adenylate cyclase signaling cascade by inhibiting forskolin-stimulated cAMP accumulation which consequently led to a decrease in protein kinase A activity and the binding of transcription factors to a CRE consensus sequence. Likewise, an inhibition of phorbol 12-myristate 13-acetate (PMA)/ionomycin-induced interleukin 2 (IL-2) protein secretion, which correlated to decreased IL-2 gene transcription, was induced by both cannabinol and Delta9-THC. Further, cannabinoid treatment also decreased PMA/ionomycin-induced nuclear factor binding to the AP-1 proximal site of the IL-2 promoter. Conversely, forskolin enhanced PMA/ionomycin-induced AP-1 binding. These findings suggest that inhibition of signal transduction via the adenylate cyclase/cAMP pathway induces T-cell dysfunction which leads to a diminution in IL-2 gene transcription.

Activity of antimicrobial peptide mimetics in the oral cavity: II. Activity against periopathogenic biofilms and anti-inflammatory activity

PubMed Central

Hua, J; Scott, R.W.; Diamond, G

2011-01-01

Whereas periodontal disease is ultimately of bacterial etiology, from multispecies biofilms of gram-negative anaerobic microorganisms, much of the deleterious effects are caused by the resultant epithelial inflammatory response. Hence, development of a treatment that combines anti-biofilm antibiotic activity with anti-inflammatory activity would be of great utility. Antimicrobial peptides (AMPs) such as defensins are naturally occurring peptides that exhibit broad-spectrum activity as well as a variety of immunomodulatory activities. Furthermore, bacteria do not readily develop resistance to these agents. However, clinical studies have suggested that they do not represent optimal candidates for exogenous therapeutic agents. Small-molecule mimetics of these AMPs exhibit similar activities to the parent peptides, in addition to having low toxicity, high stability and low cost. To determine whether AMP mimetics have the potential for treatment of periodontal disease, we examined the activity of one mimetic, mPE, against biofilm cultures of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Metabolic assays as well as culture and biomass measurement assays demonstrated that mPE exhibits potent activity against biofilm cultures of both species. Furthermore, as little as 2 µg ml−1 mPE was sufficient to inhibit interleukin-1β-induced secretion of interleukin-8 in both gingival epithelial cells and THP-1 cells. This anti-inflammatory activity is associated with a reduction in activation of nuclear factor-κB, suggesting that mPE can act both as an anti-biofilm agent in an anaerobic environment and as an anti-inflammatory agent in infected tissues. PMID:21040516

C/EBPβ (CCAAT/enhancer-binding protein β) mediates progesterone production through transcriptional regulation in co-operation with SF-1 (steroidogenic factor-1).

PubMed

Mizutani, Tetsuya; Ju, Yunfeng; Imamichi, Yoshitaka; Osaki, Tsukasa; Yazawa, Takashi; Kawabe, Shinya; Ishikane, Shin; Matsumura, Takehiro; Kanno, Masafumi; Kamiki, Yasue; Kimura, Kohei; Minamino, Naoto; Miyamoto, Kaoru

2014-06-15

The transcription factor SF-1 (steroidogenic factor-1) is a master regulator of steroidogenesis. Previously, we have found that SF-1 induces the differentiation of mesenchymal stem cells into steroidogenic cells. To elucidate the molecular mechanisms of SF-1-mediated functions, we attempted to identify protein components of the SF-1 nuclear protein complex in differentiated cells. SF-1 immunoaffinity chromatography followed by MS/MS analysis was performed, and 24 proteins were identified. Among these proteins, we focused on C/EBPβ (CCAAT/enhancer-binding protein β), which is an essential transcription factor for ovulation and luteinization, as the transcriptional mechanisms of C/EBPβ working together with SF-1 are poorly understood. C/EBPβ knockdown attenuated cAMP-induced progesterone production in granulosa tumour-derived KGN cells by altering STAR (steroidogenic acute regulatory protein), CYP11A1 (cytochrome P450, family 11, subfamily A, polypeptide 1) and HSD3B2 (hydroxy-δ-5-steroid dehydrogenase, 3β- and steroid δ-isomerase 2) expression. EMSA and ChIP assays revealed novel C/EBPβ-binding sites in the upstream regions of the HSD3B2 and CYP11A1 genes. These interactions were enhanced by cAMP stimulation. Luciferase assays showed that C/EBPβ-responsive regions were found in each promoter and C/EBPβ is involved in the cAMP-induced transcriptional activity of these genes together with SF-1. These results indicate that C/EBPβ is an important mediator of progesterone production by working together with SF-1, especially under tropic hormone-stimulated conditions.

Multi-layered nanoparticles for penetrating the endosome and nuclear membrane via a step-wise membrane fusion process.

PubMed

Akita, Hidetaka; Kudo, Asako; Minoura, Arisa; Yamaguti, Masaya; Khalil, Ikramy A; Moriguchi, Rumiko; Masuda, Tomoya; Danev, Radostin; Nagayama, Kuniaki; Kogure, Kentaro; Harashima, Hideyoshi

2009-05-01

Efficient targeting of DNA to the nucleus is a prerequisite for effective gene therapy. The gene-delivery vehicle must penetrate through the plasma membrane, and the DNA-impermeable double-membraned nuclear envelope, and deposit its DNA cargo in a form ready for transcription. Here we introduce a concept for overcoming intracellular membrane barriers that involves step-wise membrane fusion. To achieve this, a nanotechnology was developed that creates a multi-layered nanoparticle, which we refer to as a Tetra-lamellar Multi-functional Envelope-type Nano Device (T-MEND). The critical structural elements of the T-MEND are a DNA-polycation condensed core coated with two nuclear membrane-fusogenic inner envelopes and two endosome-fusogenic outer envelopes, which are shed in stepwise fashion. A double-lamellar membrane structure is required for nuclear delivery via the stepwise fusion of double layered nuclear membrane structure. Intracellular membrane fusions to endosomes and nuclear membranes were verified by spectral imaging of fluorescence resonance energy transfer (FRET) between donor and acceptor fluorophores that had been dually labeled on the liposome surface. Coating the core with the minimum number of nucleus-fusogenic lipid envelopes (i.e., 2) is essential to facilitate transcription. As a result, the T-MEND achieves dramatic levels of transgene expression in non-dividing cells.

PREFACE: XXXVI Symposium on Nuclear Physics (Cocoyoc 2013)

NASA Astrophysics Data System (ADS)

Barrón-Palos, Libertad; Morales-Agiss, Irving; Martínez-Quiroz, Enrique

2014-03-01

logo The XXXVI Symposium on Nuclear Physics, organized by the Division of Nuclear Physics of the Mexican Physical Society, took place from 7-10 January, 2013. As it is customary, the Symposium was held at the Hotel Hacienda Cocoyoc, in the state of Morelos, Mexico. Conference photograph This international venue with many years of tradition was attended by outstanding physicists, some of them already regulars to this meeting and others who joined us for the first time; a total of 45 attendees from different countries (Argentina, Brazil, Canada, China, Germany, Italy, Japan, Mexico and the United States). A variety of topics related to nuclear physics (nuclear reactions, radioactive beams, nuclear structure, fundamental neutron physics, sub-nuclear physics and nuclear astrophysics, among others) were presented in 26 invited talks and 10 contributed posters. Local Organizing Committee Libertad Barrón-Palos (IF-UNAM)) Enrique Martínez-Quíroz (ININ)) Irving Morales-Agiss (ICN-UNAM)) International Advisory Committee Osvaldo Civitarese (UNLP, Argentina) Jerry P Draayer (LSU, USA)) Alfredo Galindo-Uribarri (ORNL, USA)) Paulo Gomes (UFF, Brazil)) Piet Van Isacker (GANIL, France)) James J Kolata (UND, USA)) Reiner Krücken (TRIUMF, Canada)) Jorge López (UTEP, USA)) Stuart Pittel (UD, USA)) W Michael Snow (IU, USA)) Adam Szczepaniak (IU, USA)) Michael Wiescher (UND, USA)) A list of participants is available in the PDF

A New Look to Nuclear Data

DOE PAGES

McCutchan, E. A.; Brown, D. A.; Sonzogni, A. A.

2017-03-30

Databases of evaluated nuclear data form a cornerstone on which we build academic nuclear structure physics, reaction physics, astrophysics, and many applied nuclear technologies. In basic research, nuclear data are essential for selecting, designing and conducting experiments, and for the development and testing of theoretical models to understand the fundamental properties of atomic nuclei. Likewise, the applied fields of nuclear power, homeland security, stockpile stewardship and nuclear medicine, all have deep roots requiring evaluated nuclear data. Each of these fields requires rapid and easy access to up-to-date, comprehensive and reliable databases. The DOE-funded US Nuclear Data Program is a specificmore » and coordinated effort tasked to compile, evaluate and disseminate nuclear structure and reaction data such that it can be used by the world-wide nuclear physics community.« less