Establishment of optimized MDCK cell lines for reliable efflux transport studies.

PubMed

Gartzke, Dominik; Fricker, Gert

2014-04-01

Madin-Darby canine kidney (MDCK) cells transfected with human MDR1 gene (MDCK-MDR1) encoding for P-glycoprotein (hPgp, ABCB1) are widely used for transport studies to identify drug candidates as substrates of this efflux protein. Therefore, it is necessary to rely on constant and comparable expression levels of Pgp to avoid false negative or positive results. We generated a cell line with homogenously high and stable expression of hPgp through sorting single clones from a MDCK-MDR1 cell pool using fluorescence-activated cell sorting (FACS). To obtain control cell lines for evaluation of cross-interactions with endogenous canine Pgp (cPgp) wild-type cells were sorted with a low expression pattern of cPgp in comparison with the MDCK-MDR1. Expression of other transporters was also characterized in both cell lines by quantitative real-time PCR and Western blot. Pgp function was investigated applying the Calcein-AM assay as well as bidirectional transport assays using (3) H-Digoxin, (3) H-Vinblastine, and (3) H-Quinidine as substrates. Generated MDCK-MDR1 cell lines showed high expression of hPgp. Control MDCK-WT cells were optimized in showing a comparable expression level of cPgp in comparison with MDCK-MDR1 cell lines. Generated cell lines showed higher and more selective Pgp transport compared with parental cells. Therefore, they provide a significant improvement in the performance of efflux studies yielding more reliable results. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

H-beta line variability in magnetic Ap stars. I

NASA Technical Reports Server (NTRS)

Madej, J.; Jahn, K.; Stepien, K.

1984-01-01

Preliminary results of photometric measurements of H-beta in several Ap stars are presented. Periodic variations are found certainly in Theta Aur and Alpha (2) CVn, and possibly in Phi Dra. For the other stars upper limits for variations of H-beta are determined. Observed amplitudes are transformed into variations of equivalent width assuming specific profile variations. The results show that variations of equivalent width of H-beta in the stars investigated are of the order of 10 percent or less.

Beam Transport of 4 GeV Protons from AGS to the Proton Interrogation Target of the Neutrino Line (Z_line) and Effect of the Air on the Transported Beam

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

Tsoupas,N.; Ahrens, L.; Pile, P.

2008-10-01

As part of the preparation for the Proton Interrogation Experiment, we have calculated the beam optics for the transport of 4 GeV protons, from the AGS extraction point, to the 'Cross-Section Target Wheel 1' and to the 'Proton Interrogation Target'. In this technical note we present three possible beam-transports each corresponding to a particular Fast Extracted Beam W B setup of the AGS. In addition we present results on the effect of the atmospheric air, (which fills the drift space of the last 100 [m] of the transport line), on the size of the beam, at two locations along themore » drift space, one location at the middle of the drift space and the other at the end where the 'Proton Interrogation Target' is placed. All the beam transports mentioned above require the removal of the WD1 dipole magnet, which is the first magnet of the W-line, because it acts as a limiting beam aperture, and the magnet is not used in the beam transport. An alternative solution of a beam transport, which does not require the removal of the WD1 magnet, is also presented. In this solution, which models the transport line using the TURTLE computer code[7], the vertical beam sizes at the location of the WD1 magnet is minimized to allow 'lossless' beam transport at the location of the WD1 magnet. A similar solution, but using a MAD model of the line, is also presented.« less

Development and evaluation of human AP endonuclease inhibitors in melanoma and glioma cell lines.

PubMed

Mohammed, M Z; Vyjayanti, V N; Laughton, C A; Dekker, L V; Fischer, P M; Wilson, D M; Abbotts, R; Shah, S; Patel, P M; Hickson, I D; Madhusudan, S

2011-02-15

Modulation of DNA base excision repair (BER) has the potential to enhance response to chemotherapy and improve outcomes in tumours such as melanoma and glioma. APE1, a critical protein in BER that processes potentially cytotoxic abasic sites (AP sites), is a promising new target in cancer. In the current study, we aimed to develop small molecule inhibitors of APE1 for cancer therapy. An industry-standard high throughput virtual screening strategy was adopted. The Sybyl8.0 (Tripos, St Louis, MO, USA) molecular modelling software suite was used to build inhibitor templates. Similarity searching strategies were then applied using ROCS 2.3 (Open Eye Scientific, Santa Fe, NM, USA) to extract pharmacophorically related subsets of compounds from a chemically diverse database of 2.6 million compounds. The compounds in these subsets were subjected to docking against the active site of the APE1 model, using the genetic algorithm-based programme GOLD2.7 (CCDC, Cambridge, UK). Predicted ligand poses were ranked on the basis of several scoring functions. The top virtual hits with promising pharmaceutical properties underwent detailed in vitro analyses using fluorescence-based APE1 cleavage assays and counter screened using endonuclease IV cleavage assays, fluorescence quenching assays and radiolabelled oligonucleotide assays. Biochemical APE1 inhibitors were then subjected to detailed cytotoxicity analyses. Several specific APE1 inhibitors were isolated by this approach. The IC(50) for APE1 inhibition ranged between 30 nM and 50 μM. We demonstrated that APE1 inhibitors lead to accumulation of AP sites in genomic DNA and potentiated the cytotoxicity of alkylating agents in melanoma and glioma cell lines. Our study provides evidence that APE1 is an emerging drug target and could have therapeutic application in patients with melanoma and glioma.

The absorption and transport of magnolol in Caco-2 cell model.

PubMed

Wu, An-Guo; Zeng, Bao; Huang, Meng-Qiu; Li, Sheng-Mei; Chen, Jian-Nan; Lai, Xiao-Ping

2013-03-01

To investigate the absorption and transport mechanism of magnolol in Caco-2 cell model. A human intestinal epithelial cell model Caco-2 cell in vitro cultured was applied to study the absorption and transport of magnolol, the effects of time, donor concentration, P-gp inhibitor verapamil, pH and temperature on the absorption and transport of magnolol were investigated. The determination of magnolol was performed by high performance liquid chromatography, then the values of apparent permeability coefficient (P app ) and P ratio Basolateral-to-Apical (BL-to-AP)/Apical-to-Basolateral (AP-to-BL) were calculated. In Caco-2 cell model, comparing the amounts of transport of AP-to-BL and BL-to-AP, the latter was larger. At the same donor concentration, either the amounts of transport of AP-to-BL or BL-to-AP increased with increase in donor concentration and incubation time. Verapamil could significantly improve the amounts of transport of AP-to-BL. The transport of AP-to-BL and BL-to-AP depended on temperature, and there was no significant effect of pH on the transport of AP-to-BL. Magnolol could be transported through the intestinal mucosa via a passive diffusion mechanism primarily, coexisting with a carrier-mediated transport, at the same time, the efflux mechanism could be involved.

Diadenosine polyphosphates Ap3A and Ap4A, but not Ap5A or Ap6A, induce proliferation of vascular smooth muscle cells.

PubMed

Bobbert, Peter; Schlüter, Hartmut; Schultheiss, Heinz Peter; Reusch, Hans Peter

2008-05-15

Depending on the number of phosphate groups, diadenosine polyphosphates (ApnA, Ap3A, Ap4A, Ap5A and Ap6A) differ in properties such as proliferation, apoptosis, vasoconstriction and vasodilatation of vascular smooth muscle cells (VSMCs). Possible signaling pathways leading to effects such as proliferation are still unknown. This study examined the proliferative effects of diadenosine polyphosphates on VSMCs and their intracellular pathways. Proliferation of VSMCs was measured by the cell count and [(3)H] thymidine incorporation. Phosphorylation of the MAP kinases ERK1/2 was determined by Western blotting. Single-cell [Ca(2+)](i) measurements were done to determine the influence of [Ca(2+)](i) on intracellular signaling. Stress fiber formation was assessed by fluorescence microscopy to detect an influence of G alpha(12). Ap3A and Ap4A, but not Ap5A or Ap6A, were shown to increase proliferation of VSMCs by activating P2Y receptors, which leads to stimulation of the Ras-Raf-MEK-ERK1/2 cascade. Ap3A- and Ap4A-induced activation of the MAP kinases ERK1/2 was dependent on a signaling pathway that included the EGF receptor, PKC, PLCbeta and the increase of [Ca(2+)](i). In conclusion, Ap3A and Ap4A, but not Ap5A or Ap6A, induce proliferation of VSMCs by a signaling pathway that begins with activation of P2Y receptors and leads to stimulation of the MAP kinases ERK1/2.

Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly

PubMed Central

Hardies, Katia; May, Patrick; Djémié, Tania; Tarta-Arsene, Oana; Deconinck, Tine; Craiu, Dana; Helbig, Ingo; Suls, Arvid; Balling, Rudy; Weckhuysen, Sarah; De Jonghe, Peter; Hirst, Jennifer; Afawi, Zaid; Barisic, Nina; Baulac, Stéphanie; Caglayan, Hande; Depienne, Christel; De Kovel, Carolien G.F.; Dimova, Petia; Guerrero-López, Rosa; Guerrini, Renzo; Hjalgrim, Helle; Hoffman-Zacharska, Dorota; Jahn, Johanna; Klein, Karl Martin; Koeleman, Bobby P.C.; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes; Lerche, Holger; Marini, Carla; Muhle, Hiltrud; Rosenow, Felix; Serratosa, Jose M.; Møller, Rikke S.; Stephani, Ulrich; Striano, Pasquale; Talvik, Tiina; Von Spiczak, Sarah; Weber, Yvonne; Zara, Federico

2015-01-01

We report two siblings with infantile onset seizures, severe developmental delay and spastic paraplegia, in whom whole-genome sequencing revealed compound heterozygous mutations in the AP4S1 gene, encoding the σ subunit of the adaptor protein complex 4 (AP-4). The effect of the predicted loss-of-function variants (p.Gln46Profs*9 and p.Arg97*) was further investigated in a patient's fibroblast cell line. We show that the premature stop mutations in AP4S1 result in a reduction of all AP-4 subunits and loss of AP-4 complex assembly. Recruitment of the AP-4 accessory protein tepsin, to the membrane was also abolished. In retrospect, the clinical phenotype in the family is consistent with previous reports of the AP-4 deficiency syndrome. Our study reports the second family with mutations in AP4S1 and describes the first two patients with loss of AP4S1 and seizures. We further discuss seizure phenotypes in reported patients, highlighting that seizures are part of the clinical manifestation of the AP-4 deficiency syndrome. We also hypothesize that endosomal trafficking is a common theme between heritable spastic paraplegia and some inherited epilepsies. PMID:25552650

Loss of AP-5 results in accumulation of aberrant endolysosomes: defining a new type of lysosomal storage disease

PubMed Central

Hirst, Jennifer; Edgar, James R.; Esteves, Typhaine; Darios, Frédéric; Madeo, Marianna; Chang, Jaerak; Roda, Ricardo H.; Dürr, Alexandra; Anheim, Mathieu; Gellera, Cinzia; Li, Jun; Züchner, Stephan; Mariotti, Caterina; Stevanin, Giovanni; Blackstone, Craig; Kruer, Michael C.; Robinson, Margaret S.

2015-01-01

Adaptor proteins (AP 1–5) are heterotetrameric complexes that facilitate specialized cargo sorting in vesicular-mediated trafficking. Mutations in AP5Z1, encoding a subunit of the AP-5 complex, have been reported to cause hereditary spastic paraplegia (HSP), although their impact at the cellular level has not been assessed. Here we characterize three independent fibroblast lines derived from skin biopsies of patients harbouring nonsense mutations in AP5Z1 and presenting with spastic paraplegia accompanied by neuropathy, parkinsonism and/or cognitive impairment. In all three patient-derived lines, we show that there is complete loss of AP-5 ζ protein and a reduction in the associated AP-5 µ5 protein. Using ultrastructural analysis, we show that these patient-derived lines consistently exhibit abundant multilamellar structures that are positive for markers of endolysosomes and are filled with aberrant storage material organized as exaggerated multilamellar whorls, striated belts and ‘fingerprint bodies’. This phenotype can be replicated in a HeLa cell culture model by siRNA knockdown of AP-5 ζ. The cellular phenotype bears striking resemblance to features described in a number of lysosomal storage diseases (LSDs). Collectively, these findings reveal an emerging picture of the role of AP-5 in endosomal and lysosomal homeostasis, illuminates a potential pathomechanism that is relevant to the role of AP-5 in neurons and expands the understanding of recessive HSPs. Moreover, the resulting accumulation of storage material in endolysosomes leads us to propose that AP-5 deficiency represents a new type of LSDs. PMID:26085577

Comparative transcriptome profiling of upland (VS16) and lowland (AP13) ecotypes of switchgrass.

PubMed

Ayyappan, Vasudevan; Saha, Malay C; Thimmapuram, Jyothi; Sripathi, Venkateswara R; Bhide, Ketaki P; Fiedler, Elizabeth; Hayford, Rita K; Kalavacharla, Venu Kal

2017-01-01

Transcriptomes of two switchgrass genotypes representing the upland and lowland ecotypes will be key tools in switchgrass genome annotation and biotic and abiotic stress functional genomics. Switchgrass (Panicum virgatum L.) is an important bioenergy feedstock for cellulosic ethanol production. We report genome-wide transcriptome profiling of two contrasting tetraploid switchgrass genotypes, VS16 and AP13, representing the upland and lowland ecotypes, respectively. A total of 268 million Illumina short reads (50 nt) were generated, of which, 133 million were obtained in AP13 and the rest 135 million in VS16. More than 90% of these reads were mapped to the switchgrass reference genome (V1.1). We identified 6619 and 5369 differentially expressed genes in VS16 and AP13, respectively. Gene ontology and KEGG pathway analysis identified key genes that regulate important pathways including C4 photosynthesis, photorespiration and phenylpropanoid metabolism. A series of genes (33) involved in photosynthetic pathway were up-regulated in AP13 but only two genes showed higher expression in VS16. We identified three dicarboxylate transporter homologs that were highly expressed in AP13. Additionally, genes that mediate drought, heat, and salinity tolerance were also identified. Vesicular transport proteins, syntaxin and signal recognition particles were seen to be up-regulated in VS16. Analyses of selected genes involved in biosynthesis of secondary metabolites, plant-pathogen interaction, membrane transporters, heat, drought and salinity stress responses confirmed significant variation in the relative expression reflected in RNA-Seq data between VS16 and AP13 genotypes. The phenylpropanoid pathway genes identified here are potential targets for biofuel conversion.

Sorting of Pmel17 to melanosomes through the plasma membrane by AP1 and AP2: evidence for the polarized nature of melanocytes

PubMed Central

Valencia, Julio C.; Watabe, Hidenori; Chi, An; Rouzaud, Francois; Chen, Kevin G.; Vieira, Wilfred D.; Takahashi, Kaoruko; Yamaguchi, Yuji; Berens, Werner; Nagashima, Kunio; Shabanowitz, Jeffrey; Hunt, Donald F.; Appella, Ettore; Hearing, Vincent J.

2015-01-01

Summary Adaptor proteins (AP) play important roles in the sorting of proteins from the trans-Golgi network, but how they function in the sorting of various melanosome-specific proteins such as Pmel17, an essential structural component of melanosomes, in melanocytes is unknown. We characterized the processing and trafficking of Pmel17 via adaptor protein complexes within melanocytic cells. Proteomics analysis detected Pmel17, AP1 and AP2, but not AP3 or AP4 in early melanosomes. Real-time PCR, immunolabeling and tissue in-situ hybridization confirmed the coexpression of AP1 isoforms μ1A and μ1B (expressed only in polarized cells) in melanocytes and keratinocytes, but expression of μ1B is missing in some melanoma cell lines. Transfection with AP1 isoforms (μ1A or μ1B) showed two distinct distribution patterns that involved Pmel17, and only μ1B was able to restore the sorting of Pmel17 to the plasma membrane in cells lacking μ1B expression. Finally, we established that expression of μ1B is regulated physiologically in melanocytes by UV radiation or DKK1. These results show that Pmel17 is sorted to melanosomes by various intracellular routes, directly or indirectly through the plasma membrane, and the presence of basolateral elements in melanocytes suggests their polarized nature. PMID:16492709

The Broad-Lined Type Ic SN 2012ap and the Nature of Relativistic Supernovae Lacking a Gamma-Ray Burst Detection

NASA Technical Reports Server (NTRS)

Milisavljevic, D.; Margutti, R.; Parrent, J. T.; Soderberg, A. M.; Fesen, R. A.; Mazzali, P.; Maeda, K.; Sanders, N. E.; Cenko, S. B.; Silverman, J. M.

2014-01-01

We present ultraviolet, optical, and near-infrared observations of SN2012ap, a broad-lined Type Ic supernova in the galaxy NGC 1729 that produced a relativistic and rapidly decelerating outflow without a gamma-ray burst signature. Photometry and spectroscopy follow the flux evolution from -13 to +272 days past the B-band maximum of -17.4 +/- 0.5 mag. The spectra are dominated by Fe II, O I, and Ca II absorption lines at ejecta velocities of v approx. 20,000 km s(exp. -1) that change slowly over time. Other spectral absorption lines are consistent with contributions from photospheric He I, and hydrogen may also be present at higher velocities (v approx. greater than 27,000 km s(exp. -1)). We use these observations to estimate explosion properties and derive a total ejecta mass of 2.7 Solar mass, a kinetic energy of 1.0×1052 erg, and a (56)Ni mass of 0.1-0.2 Solar mass. Nebular spectra (t > 200 d) exhibit an asymmetric double-peaked [O I] lambda lambda 6300, 6364 emission profile that we associate with absorption in the supernova interior, although toroidal ejecta geometry is an alternative explanation. SN2012ap joins SN2009bb as another exceptional supernova that shows evidence for a central engine (e.g., black-hole accretion or magnetar) capable of launching a non-negligible portion of ejecta to relativistic velocities without a coincident gamma-ray burst detection. Defining attributes of their progenitor systems may be related to notable properties including above-average environmental metallicities of Z approx. greater than Solar Z, moderate to high levels of host-galaxy extinction (E(B -V ) > 0.4 mag), detection of high-velocity helium at early epochs, and a high relative flux ratio of [Ca II]/[O I] > 1 at nebular epochs. These events support the notion that jet activity at various energy scales may be present in a wide range of supernovae.

Comparison of a CCD and an APS for soft X-ray diffraction

NASA Astrophysics Data System (ADS)

Stewart, Graeme; Bates, R.; Blue, A.; Clark, A.; Dhesi, S. S.; Maneuski, D.; Marchal, J.; Steadman, P.; Tartoni, N.; Turchetta, R.

2011-12-01

We compare a new CMOS Active Pixel Sensor (APS) to a Princeton Instruments PIXIS-XO: 2048B Charge Coupled Device (CCD) with soft X-rays tested in a synchrotron beam line at the Diamond Light Source (DLS). Despite CCDs being established in the field of scientific imaging, APS are an innovative technology that offers advantages over CCDs. These include faster readout, higher operational temperature, in-pixel electronics for advanced image processing and reduced manufacturing cost. The APS employed was the Vanilla sensor designed by the MI3 collaboration and funded by an RCUK Basic technology grant. This sensor has 520 x 520 square pixels, of size 25 μm on each side. The sensor can operate at a full frame readout of up to 20 Hz. The sensor had been back-thinned, to the epitaxial layer. This was the first time that a back-thinned APS had been demonstrated at a beam line at DLS. In the synchrotron experiment soft X-rays with an energy of approximately 708 eV were used to produce a diffraction pattern from a permalloy sample. The pattern was imaged at a range of integration times with both sensors. The CCD had to be operated at a temperature of -55°C whereas the Vanilla was operated over a temperature range from 20°C to -10°C. We show that the APS detector can operate with frame rates up to two hundred times faster than the CCD, without excessive degradation of image quality. The signal to noise of the APS is shown to be the same as that of the CCD at identical integration times and the response is shown to be linear, with no charge blooming effects. The experiment has allowed a direct comparison of back thinned APS and CCDs in a real soft x-ray synchrotron experiment.

AP-1/KIF13A Blocking Peptides Impair Melanosome Maturation and Melanin Synthesis.

PubMed

Campagne, Cécile; Ripoll, Léa; Gilles-Marsens, Floriane; Raposo, Graça; Delevoye, Cédric

2018-02-14

Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from endosomes to maturing melanosomes. Among the proteins controlling endosome-melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting and trafficking of TYRP1 to melanosomes. We identify here β1-adaptin AP-1 subunit-derived peptides of 5 amino acids that block the interaction of KIF13A with AP-1 in cells. Incubating these peptides with human MNT-1 cells or 3D-reconstructed pigmented epidermis decreases pigmentation by impacting the maturation of melanosomes in fully pigmented organelles. This study highlights that peptides targeting the intracellular trafficking of melanocytes are candidate molecules to tune pigmentation in health and disease.

AP-1/KIF13A Blocking Peptides Impair Melanosome Maturation and Melanin Synthesis

PubMed Central

Campagne, Cécile; Ripoll, Léa; Gilles-Marsens, Floriane; Raposo, Graça

2018-01-01

Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from endosomes to maturing melanosomes. Among the proteins controlling endosome-melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting and trafficking of TYRP1 to melanosomes. We identify here β1-adaptin AP-1 subunit-derived peptides of 5 amino acids that block the interaction of KIF13A with AP-1 in cells. Incubating these peptides with human MNT-1 cells or 3D-reconstructed pigmented epidermis decreases pigmentation by impacting the maturation of melanosomes in fully pigmented organelles. This study highlights that peptides targeting the intracellular trafficking of melanocytes are candidate molecules to tune pigmentation in health and disease. PMID:29443872

Noise test-resilient wheels Massachusetts Bay Transportation Authority green line

DOT National Transportation Integrated Search

1982-11-30

This document presents the results of noise and ground-borne vibration measurements made for three rail transit vehicles operating on the Green Line of the Massachusetts Bay Transportation Authority (MBTA). The purpose of these measurements was to as...

Tank 241-AP-106, Grab samples, 6AP-98-1, 6AP-98-2 and 6AP-98-3 Analytical results for the final report

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

FULLER, R.K.

1999-02-23

This document is the final report for tank 241-AP-106 grab samples. Three grab samples 6AP-98-1, 6AP-98-2 and 6AP-98-3 were taken from riser 1 of tank 241-AP-106 on May 28, 1998 and received by the 222-S Laboratory on May 28, 1998. Analyses were performed in accordance with the ''Compatability Grab Sampling and Analysis Plan'' (TSAP) (Sasaki, 1998) and the ''Data Quality Objectives for Tank Farms Waste Compatability Program (DQO). The analytical results are presented in the data summary report. No notification limits were exceeded. The request for sample analysis received for AP-106 indicated that the samples were polychlorinated biphenyl (PCB) suspects.more » The results of this analysis indicated that no PCBs were present at the Toxic Substance Control Act (TSCA) regulated limit of 50 ppm. The results and raw data for the PCB analysis are included in this document.« less

Electronic transport of bilayer graphene with asymmetry line defects

NASA Astrophysics Data System (ADS)

Zhao, Xiao-Ming; Wu, Ya-Jie; Chen, Chan; Liang, Ying; Kou, Su-Peng

2016-11-01

In this paper, we study the quantum properties of a bilayer graphene with (asymmetry) line defects. The localized states are found around the line defects. Thus, the line defects on one certain layer of the bilayer graphene can lead to an electric transport channel. By adding a bias potential along the direction of the line defects, we calculate the electric conductivity of bilayer graphene with line defects using the Landauer-Büttiker theory, and show that the channel affects the electric conductivity remarkably by comparing the results with those in a perfect bilayer graphene. This one-dimensional line electric channel has the potential to be applied in nanotechnology engineering. Project supported by the National Basic Research Program of China (Grant Nos. 2011CB921803 and 2012CB921704), the National Natural Science Foundation of China (Grant Nos. 11174035, 11474025, 11504285, and 11404090), the Specialized Research Fund for the Doctoral Program of Higher Education, China, the Fundamental Research Funds for the Central Universities, China, the Scientific Research Program Fund of the Shaanxi Provincial Education Department, China (Grant No. 15JK1363), and the Young Talent Fund of University Association for Science and Technology in Shaanxi Province, China.

Transport of IRW, an ovotransferrin-derived antihypertensive peptide, in human intestinal epithelial Caco-2 cells.

PubMed

Bejjani, Satyanarayana; Wu, Jianping

2013-02-20

IRW is an egg ovotransferrin-derived ACE inhibitory peptide. The purpose of this study was to evaluate the stability and transcellular transport of IRW in Caco-2 cell monolayers. The stability of IRW was monitored on the apical (AP) surface while its transport was studied from AP to basal (BL) and from BL to AP surfaces. The results revealed that IRW is resistant against intestinal peptidase up to 60 min. Transport of IRW was not affected by addition of wortamanin, a transcytosis inhibitor. However, in the presence of cytochalasin D, a gap junction disruptor, transport of IRW was significantly increased, suggesting a possible passive transport from AP to BL surface. A higher transport of IRW from AP to BL surface than that from BL to AP surface suggests a passive-mediated transport. Moreover, in the presence of glycyl-sarcosine, a substrate for peptide transporter PepT 1, transport of IRW was reduced from AP to BL surface. The above observations showed atypical transport of IRW in Caco-2 cell monolayers. Thus, IRW may possibly be absorbed intact into the site of action for controlling hypertension.

Topological transport in Dirac nodal-line semimetals

NASA Astrophysics Data System (ADS)

Rui, W. B.; Zhao, Y. X.; Schnyder, Andreas P.

2018-04-01

Topological nodal-line semimetals are characterized by one-dimensional Dirac nodal rings that are protected by the combined symmetry of inversion P and time-reversal T . The stability of these Dirac rings is guaranteed by a quantized ±π Berry phase and their low-energy physics is described by a one-parameter family of (2+1)-dimensional quantum field theories exhibiting the parity anomaly. Here we study the Berry-phase supported topological transport of P T -invariant nodal-line semimetals. We find that small inversion breaking allows for an electric-field-induced anomalous transverse current, whose universal component originates from the parity anomaly. Due to this Hall-like current, carriers at opposite sides of the Dirac nodal ring flow to opposite surfaces when an electric field is applied. To detect the topological currents, we propose a dumbbell device, which uses surface states to filter charges based on their momenta. Suggestions for experiments and device applications are discussed.

Coaching Strategies for AP: Building a Successful AP European History Program

ERIC Educational Resources Information Center

Fornaciari, Jim

2014-01-01

The October 2013 special issue of "Social Education" dealt with almost all AP social studies subjects, but omitted AP European History. This is one of the most fascinating AP subjects for students and teachers alike. In this article, the author shares his experiences since hewas given the responsibility of building his school's Advanced…

AP1000{sup R} nuclear power plant safety overview for spent fuel cooling

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

Gorgemans, J.; Mulhollem, L.; Glavin, J.

2012-07-01

The AP1000{sup R} plant is an 1100-MWe class pressurized water reactor with passive safety features and extensive plant simplifications that enhance construction, operation, maintenance, safety and costs. The AP1000 design uses passive features to mitigate design basis accidents. The passive safety systems are designed to function without safety-grade support systems such as AC power, component cooling water, service water or HVAC. Furthermore, these passive features 'fail safe' during a non-LOCA event such that DC power and instrumentation are not required. The AP1000 also has simple, active, defense-in-depth systems to support normal plant operations. These active systems provide the first levelmore » of defense against more probable events and they provide investment protection, reduce the demands on the passive features and support the probabilistic risk assessment. The AP1000 passive safety approach allows the plant to achieve and maintain safe shutdown in case of an accident for 72 hours without operator action, meeting the expectations provided in the U.S. Utility Requirement Document and the European Utility Requirements for passive plants. Limited operator actions are required to maintain safe conditions in the spent fuel pool via passive means. In line with the AP1000 approach to safety described above, the AP1000 plant design features multiple, diverse lines of defense to ensure spent fuel cooling can be maintained for design-basis events and beyond design-basis accidents. During normal and abnormal conditions, defense-in-depth and other systems provide highly reliable spent fuel pool cooling. They rely on off-site AC power or the on-site standby diesel generators. For unlikely design basis events with an extended loss of AC power (i.e., station blackout) or loss of heat sink or both, spent fuel cooling can still be provided indefinitely: - Passive systems, requiring minimal or no operator actions, are sufficient for at least 72 hours under all

Generation of genome-modified Drosophila cell lines using SwAP.

PubMed

Franz, Alexandra; Brunner, Erich; Basler, Konrad

2017-10-02

The ease of generating genetically modified animals and cell lines has been markedly increased by the recent development of the versatile CRISPR/Cas9 tool. However, while the isolation of isogenic cell populations is usually straightforward for mammalian cell lines, the generation of clonal Drosophila cell lines has remained a longstanding challenge, hampered by the difficulty of getting Drosophila cells to grow at low densities. Here, we describe a highly efficient workflow to generate clonal Cas9-engineered Drosophila cell lines using a combination of cell pools, limiting dilution in conditioned medium and PCR with allele-specific primers, enabling the efficient selection of a clonal cell line with a suitable mutation profile. We validate the protocol by documenting the isolation, selection and verification of eight independently Cas9-edited armadillo mutant Drosophila cell lines. Our method provides a powerful and simple workflow that improves the utility of Drosophila cells for genetic studies with CRISPR/Cas9.

Identification and embryonic expression of a new AP-2 transcription factor, AP-2 epsilon.

PubMed

Wang, Hao-Ven; Vaupel, Kristina; Buettner, Reinhard; Bosserhoff, Anja-Katrin; Moser, Markus

2004-09-01

AP-2 proteins comprise a family of highly related transcription factors, which are expressed during mouse embryogenesis in a variety of ectodermal, neuroectodermal, and mesenchymal tissues. AP-2 transcription factors were shown to be involved in morphogenesis of craniofacial, urogenital, neural crest-derived, and placental tissues. By means of a partial cDNA fragment identified during an expressed sequence tag search for AP-2 genes, we identified a fifth, previously unknown AP-2-related gene, AP-2 epsilon. AP-2 epsilon encodes an open reading frame of 434 amino acids, which reveals the typical modular structure of AP-2 transcription factors with highly conserved C-terminal DNA binding and dimerization domains. Although the N-terminally localized activation domain is less homologous, position and identity of amino acids essential for transcriptional transactivation are conserved. Reverse transcriptase-polymerase chain reaction analyses of murine embryos revealed AP-2 epsilon expression from gestational stage embryonic day 7.5 throughout all later embryonic stages until birth. Whole-mount in situ hybridization using a specific AP-2 epsilon cDNA fragment demonstrated that during embryogenesis, expression of AP-2 epsilon is mainly restricted to neural tissue, especially the midbrain, hindbrain, and olfactory bulb. This expression pattern was confirmed by immunohistochemistry with an AP-2 epsilon-specific antiserum. By using this antiserum, we could further localize AP-2 epsilon expression in a hypothalamic nucleus and the neuroepithelium of the vomeronasal organ, suggesting an important function of AP-2 epsilon for the development of the olfactory system.

IMPEDANCE MEASUREMENT OF VACUUM CHAMBER COMPONENTS FOR THE ADVANCE PHOTON SOURCE (APS) UPGRADE

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

Sangroula, M.; Lindberg, R.; Lill, R.

2017-06-16

The proposed Advance Photon Source Upgrade (APS-U) employs a multi-bend achromat (MBA) lattice to increase the photon brightness by two to three orders of magnitude. One of the main design challenges of the upgrade is to minimize rf heating and collective instabilities associated with the impedance of small-aperture vacuum components. As part of this effort, my research focuses on impedance measurement and simulation of various MBA vacuum components. Here, we present the summary of the impedance contributions for the APS-U and describe our planned impedance measurement technique, including some measurement results for the non-evaporative getter (NEG)-coated copper chamber and simulationmore » results for other critical components using a novel Goubau line (G-line) set up.« less

Impedance measurement of vacuum chamber components for the Advance Photon Source(APS) Upgrade

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

Sangroula, M.; Lindberg, R.; Lill, R.

2017-01-01

The proposed Advance Photon Source Upgrade (APS-U) employs a multi-bend achromat (MBA) lattice to increase the photon brightness by two to three orders of magnitude. One of the main design challenges of the upgrade is to minimize rf heating and collective instabilities associated with the impedance of small-aperture vacuum components. As part of this effort, my research focuses on impedance measurement and simulation of various MBA vacuum components. Here, we present the summary of the impedance contributions for the APS-U and describe our planned impedance measurement technique, including some measurement results for the non-evaporative getter (NEG)-coated copper chamber and simulationmore » results for other critical components using a novel Goubau line (G-line) set up.« less

Low Earth orbit assessment of proton anisotropy using AP8 and AP9 trapped proton models

NASA Astrophysics Data System (ADS)

Badavi, Francis F.; Walker, Steven A.; Santos Koos, Lindsey M.

2015-04-01

The completion of the International Space Station (ISS) in 2011 has provided the space research community with an ideal evaluation and testing facility for future long duration human activities in space. Ionized and secondary neutral particles radiation measurements inside ISS form the ideal tool for validation of radiation environmental models, nuclear reaction cross sections and transport codes. Studies using thermo-luminescent detectors (TLD), tissue equivalent proportional counter (TPEC), and computer aided design (CAD) models of early ISS configurations confirmed that, as input, computational dosimetry at low Earth orbit (LEO) requires an environmental model with directional (anisotropic) capability to properly describe the exposure of trapped protons within ISS. At LEO, ISS encounters exposure from trapped electrons, protons and geomagnetically attenuated galactic cosmic rays (GCR). For short duration studies at LEO, one can ignore trapped electrons and ever present GCR exposure contributions during quiet times. However, within the trapped proton field, a challenge arises from properly estimating the amount of proton exposure acquired. There exist a number of models to define the intensity of trapped particles. Among the established trapped models are the historic AE8/AP8, dating back to the 1980s and the recently released AE9/AP9/SPM. Since at LEO electrons have minimal exposure contribution to ISS, this work ignores the AE8 and AE9 components of the models and couples a measurement derived anisotropic trapped proton formalism to omnidirectional output from the AP8 and AP9 models, allowing the assessment of the differences between the two proton models. The assessment is done at a target point within the ISS-11A configuration (circa 2003) crew quarter (CQ) of Russian Zvezda service module (SM), during its ascending and descending nodes passes through the south Atlantic anomaly (SAA). The anisotropic formalism incorporates the contributions of proton narrow

Low Earth orbit assessment of proton anisotropy using AP8 and AP9 trapped proton models.

PubMed

Badavi, Francis F; Walker, Steven A; Santos Koos, Lindsey M

2015-04-01

The completion of the International Space Station (ISS) in 2011 has provided the space research community with an ideal evaluation and testing facility for future long duration human activities in space. Ionized and secondary neutral particles radiation measurements inside ISS form the ideal tool for validation of radiation environmental models, nuclear reaction cross sections and transport codes. Studies using thermo-luminescent detectors (TLD), tissue equivalent proportional counter (TPEC), and computer aided design (CAD) models of early ISS configurations confirmed that, as input, computational dosimetry at low Earth orbit (LEO) requires an environmental model with directional (anisotropic) capability to properly describe the exposure of trapped protons within ISS. At LEO, ISS encounters exposure from trapped electrons, protons and geomagnetically attenuated galactic cosmic rays (GCR). For short duration studies at LEO, one can ignore trapped electrons and ever present GCR exposure contributions during quiet times. However, within the trapped proton field, a challenge arises from properly estimating the amount of proton exposure acquired. There exist a number of models to define the intensity of trapped particles. Among the established trapped models are the historic AE8/AP8, dating back to the 1980s and the recently released AE9/AP9/SPM. Since at LEO electrons have minimal exposure contribution to ISS, this work ignores the AE8 and AE9 components of the models and couples a measurement derived anisotropic trapped proton formalism to omnidirectional output from the AP8 and AP9 models, allowing the assessment of the differences between the two proton models. The assessment is done at a target point within the ISS-11A configuration (circa 2003) crew quarter (CQ) of Russian Zvezda service module (SM), during its ascending and descending nodes passes through the south Atlantic anomaly (SAA). The anisotropic formalism incorporates the contributions of proton narrow

Functional Identification and Characterization of the Brassica Napus Transcription Factor Gene BnAP2, the Ortholog of Arabidopsis Thaliana APETALA2

PubMed Central

Xiong, Zhiyong; Chen, Chunli; Wang, Lijun; Yu, Jingyin; Lu, Changming; Wei, Wenhui

2012-01-01

BnAP2, an APETALA2 (AP2)-like gene, has been isolated from Brassica napus cultivar Zhongshuang 9. The cDNA of BnAP2, with 1, 299 bp in length, encoded a transcription factor comprising of 432 amino acid residues. Results from complementary experiment indicated that BnAP2 was completely capable of restoring the phenotype of Arabidopsis ap2-11 mutant. Together with the sequence and expression data, the complementation data suggested that BnAP2 encodes the ortholog of AtAP2. To address the transcriptional activation of BnAP2, we performed transactivation assays in yeast. Fusion protein of BnAP2 with GAL4 DNA binding domain strongly activated transcription in yeast, and the transactivating activity of BnAP2 was localized to the N-terminal 100 amino acids. To further study the function of BnAP2 involved in the phenotype of B. napus, we used a transgenic approach that involved targeted RNA interference (RNAi) repression induced by ihp-RNA. Floral various phenotype defectives and reduced female fertility were observed in B. napus BnAP2-RNAi lines. Loss of the function of BnAP2 gene also resulted in delayed sepal abscission and senescence with the ethylene-independent pathway. In the strong BnAP2-RNAi lines, seeds showed defects in shape, structure and development and larger size. Strong BnAP2-RNAi and wild-type seeds initially did not display a significant difference in morphology at 10 DAF, but the development of BnAP2-RNAi seeds was slower than that of wild type at 20 DAF, and further at 30 DAF, wild-type seeds were essentially at their final size, whereas BnAP2-RNAi seeds stopped growing and developing and gradually withered. PMID:22479468

Functional identification and characterization of the Brassica napus transcription factor gene BnAP2, the ortholog of Arabidopsis thaliana APETALA2.

PubMed

Yan, Xiaohong; Zhang, Lei; Chen, Bo; Xiong, Zhiyong; Chen, Chunli; Wang, Lijun; Yu, Jingyin; Lu, Changming; Wei, Wenhui

2012-01-01

BnAP2, an APETALA2 (AP2)-like gene, has been isolated from Brassica napus cultivar Zhongshuang 9. The cDNA of BnAP2, with 1, 299 bp in length, encoded a transcription factor comprising of 432 amino acid residues. Results from complementary experiment indicated that BnAP2 was completely capable of restoring the phenotype of Arabidopsis ap2-11 mutant. Together with the sequence and expression data, the complementation data suggested that BnAP2 encodes the ortholog of AtAP2. To address the transcriptional activation of BnAP2, we performed transactivation assays in yeast. Fusion protein of BnAP2 with GAL4 DNA binding domain strongly activated transcription in yeast, and the transactivating activity of BnAP2 was localized to the N-terminal 100 amino acids. To further study the function of BnAP2 involved in the phenotype of B. napus, we used a transgenic approach that involved targeted RNA interference (RNAi) repression induced by ihp-RNA. Floral various phenotype defectives and reduced female fertility were observed in B. napus BnAP2-RNAi lines. Loss of the function of BnAP2 gene also resulted in delayed sepal abscission and senescence with the ethylene-independent pathway. In the strong BnAP2-RNAi lines, seeds showed defects in shape, structure and development and larger size. Strong BnAP2-RNAi and wild-type seeds initially did not display a significant difference in morphology at 10 DAF, but the development of BnAP2-RNAi seeds was slower than that of wild type at 20 DAF, and further at 30 DAF, wild-type seeds were essentially at their final size, whereas BnAP2-RNAi seeds stopped growing and developing and gradually withered.

Diadenosine tetraphosphate (Ap4A) and triphosphate (Ap3A) signaling of human sperm motility.

PubMed

Chan, P J; Su, B C; Tredway, D R

1991-01-01

The ubiquitous dinucleotide polyphosphate, diadenosine tetraphosphate (Ap4A), has been shown to be a signal molecule for DNA replication in mammalian cells. In this study, Ap4A and a related compound, diadenosine triphosphate (Ap3A), were tested for possible signaling functions in human spermatozoa. A computerized automated semen analyzer was used to detect changes in spermatozoa motility parameters. Cryopreserved-thawed donor spermatozoa were washed and incubated in 0.1 mM Ap4A, 0.1 mM Ap3A, or control medium. The data indicated that both Ap4A and Ap3A decreased the percentage of motile spermatozoa after 4 or more hours of incubation in vitro. The two dinucleotide polyphosphates caused an increase in the amplitude of lateral spermatozoa head displacement parameter only at the start of incubation. The other spermatozoa kinematic parameters were unaffected. No opposing ying-yang dual actions of Ap4A to Ap3A were seen. From the results, Ap4A and Ap3A were observed to be potential inhibitory signals of spermatozoa motility after prolonged exposure.

Interaction Between the Broad-Lined Type Ic Supernova 2012ap and Carriers of Diffuse Interstellar Bands

NASA Technical Reports Server (NTRS)

Milisavljevic, Dan; Margutti, Raffaella; Crabtree, Kyle N.; Foster, Jonathan B.; Soderberg, Alicia M.; Fesen, Robert A.; Parrent, Jerod T.; Sanders, Nathan E.; Drout, Maria R.; Kamble, Atish;

APS Science 2006.

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

Gibson, J. M.; Fenner, R. B.; Long, G.

2007-05-24

In my five years as the Director of the Advanced Photon Source (APS), I have been fortunate to see major growth in the scientific impact from the APS. This year I am particularly enthusiastic about prospects for our longer-term future. Every scientific instrument must remain at the cutting edge to flourish. Our plans for the next generation of APS--an APS upgrade--got seriously in gear this year with strong encouragement from our users and sponsors. The most promising avenue that has emerged is the energy-recovery linac (ERL) (see article on page xx), for which we are beginning serious R&D. The ERL{at}APSmore » would offer revolutionary performance, especially for x-ray imaging and ultrafast science, while not seriously disrupting the existing user base. I am very proud of our accelerator physics and engineering staff, who not only keep the current APS at the forefront, but were able to greatly impress our international Machine Advisory Committee with the quality of their work on the possible upgrade option (see page xx). As we prepare for long-term major upgrades, our plans to develop and optimize all the sectors at APS in the near future are advancing. Several new beamlines saw first light this year, including a dedicated powder diffraction beamline (11-BM), two instruments for inelastic x-ray scattering at sector 30, and the Center for Nanoscale Materials (CNM) Nanoprobe beamline at sector 26. Our partnership in the first x-ray free-electron laser (LCLS) to be built at Stanford contributes to revolutionary growth in ultrafast science (see page xx), and we are developing a pulse chirping scheme to get ps pulses at sector 7 of the APS within a year or so. In this report, you will find selected highlights of scientific research at the APS from calendar year 2006. The highlighted work covers diverse disciplines, from fundamental to applied science. In the article on page xx you can see the direct impact of APS research on technology. Several new products have

Got AP?

ERIC Educational Resources Information Center

Digby, Joan

2016-01-01

Families, especially those considering sending their children to a private four-year university, need all the help they can get in funding college. Annmarie Guzy's essay "AP, Dual Enrollment, and the Survival of Honors Education" in this issue powerfully spells out the financial benefits that accrue from using AP courses to satisfy…

APS Science 2009.

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

Gibson, J. M; Mills, D. M.; Gerig, R.

It is my pleasure to introduce the 2009 annual report of the Advanced Photon Source. This was a very good year for us. We operated with high reliability and availability, despite growing problems with obsolete systems, and our users produced a record output of publications. The number of user experiments increased by 14% from 2008 to more than 3600. We congratulate the recipients of the 2009 Nobel Prize in Chemistry-Venkatraman Ramakrishnan (Cambridge Institute for Medical Research), Thomas Steitz (Yale University), and Ada Yonath (Weizmann Institute) - who did a substantial amount of this work at APS beamlines. Thanks to themore » efforts of our users and staff, and the ongoing counsel of the APS Scientific Advisory Committee, we made major progress in advancing our planning for the upgrade of the APS (APS-U), producing a proposal that was positively reviewed. We hope to get formal approval in 2010 to begin the upgrade. With advocacy from our users and the support of our sponsor, the Office of Basic Energy Sciences in the Department of Energy (DOE) Office of Science, our operating budgets have grown to the level needed to more adequately staff our beamlines. We were also extremely fortunate to have received $7.9 M in American Recovery and Reinvestment Act ('stimulus') funding to acquire new detectors and improve several of our beamlines. The success of the new Linac Coherent Light Source at Stanford, the world's first x-ray free-electron laser, made us particularly proud since the undulators were designed and built by the APS. Among other highlights, we note that more than one-quarter of the 46 Energy Frontier Research Centers, funded competitively across the U.S. in 2009 by the DOE, included the Advanced Photon Source in their proposed work, which shows that synchrotron radiation, and the APS in particular, are central to energy research. While APS research covers everything from fundamental to applied science (reflected by the highlights in this report), the

AP-Gate

ERIC Educational Resources Information Center

Whitman, Glenn

2003-01-01

In May 2001, students in the author's Advanced Placement (AP) United States History class were embroiled in a controversy surrounding the AP exam, in particular, having access to the exam's Document Based Question (DBQ) and free response portion prior to the test's administration. Prior to the exam, the College Board had provided a fifty-year time…

PIPELINES, TRANSMISSION LINES, AND MISCELLANEOUS TRANSPORTATION FEATURES DIGITAL LINE GRAPHS FOR THE MID-ATLANTIC INTEGRATED ASSESSMENT (MAIA) STUDY AREA

EPA Science Inventory

This data set is a geographic information system (GIS) coverage of pipelines, transmission lines, and miscellaneous transportation features for the United States Environmental Protection Agency (USEPA) Mid-Atlantic Integrated Assessment (MAIA) Project region. The coverage was p...

APS SCIENCE 2016

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

Fenner, Richard B.

The Advanced Photon Source (APS) occupies an 80-acre site on the Argonne national laboratory campus, about 25 miles from downtown chicago, illinois. it shares the site with the center for nanoscale materials and the Advanced Protein characterization facility. for directions to Argonne, see http://www.anl.gov/directions-and-visitor-information. The APS, a national synchrotron radiation research facility operated by Argonne for the u.S. department of energy (doe) office of Science, provides this nation’s brightest high-energy x-ray beams for science. research by APS users extends from the center of the earth to outer space, from new information on combustion engines and microcircuits to new drugs andmore » nanotechnologies whose scale is measured in billionths of a meter. The APS helps researchers illuminate answers to the challenges of our high-tech world, from developing new forms of energy, to sustaining our nation’s technological and economic competitiveness, to pushing back against the ravages of disease. research at the APS promises to have far-reaching« less

8 CFR 241.24 - Notice to transportation line of alien's exclusion.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Notice to transportation line of alien's exclusion. 241.24 Section 241.24 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS APPREHENSION AND DETENTION OF ALIENS ORDERED REMOVED Deportation of Excluded Aliens (for Hearings...

Numerical Test of the Additivity Principle in Anomalous Transport

NASA Astrophysics Data System (ADS)

Tamaki, Shuji

2017-10-01

The additivity principle (AP) is one of the remarkable predictions that systematically generates all information on current fluctuations once the value of average current in the linear response regime is input. However, conditions to justify the AP are still ambiguous. We hence consider three tractable models, and discuss possible conditions. The models include the harmonic chain (HC), momentum exchange (ME) model, and momentum flip (MF) model, which respectively show ballistic, anomalous, and diffusive transport. We compare the heat current cumulants predicted by the AP with exact numerical data obtained for these models. The HC does not show the AP, whereas the MF model satisfies it, as expected, since the AP was originally proposed for diffusive systems. Surprisingly, the ME model also shows the AP. The ME model is known to show the anomalous transport similar to that shown in nonlinear systems such as the Fermi-Pasta-Ulam model. Our finding indicates that general nonlinear systems may satisfy the AP. Possible conditions for satisfying the AP are discussed.

AP Music Theory Applied

ERIC Educational Resources Information Center

Spieker, Matthew H.

2016-01-01

Some American high schools include Advanced Placement (AP) Music Theory within their course offerings. Students who pass the AP exam can receive college credit either as a music or humanities credit. An AP class, however, offers music students more than future college credit; it ultimately improves musicianship skills and promotes deeper…

8 CFR 241.9 - Notice to transportation line of alien's removal.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Notice to transportation line of alien's removal. 241.9 Section 241.9 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS APPREHENSION AND DETENTION OF ALIENS ORDERED REMOVED Post-hearing Detention and Removal § 241.9...

The APETALA-2-like transcription factor OsAP2-39 controls key interactions between abscisic acid and gibberellin in rice.

PubMed

Yaish, Mahmoud W; El-Kereamy, Ashraf; Zhu, Tong; Beatty, Perrin H; Good, Allen G; Bi, Yong-Mei; Rothstein, Steven J

2010-09-09

The interaction between phytohormones is an important mechanism which controls growth and developmental processes in plants. Deciphering these interactions is a crucial step in helping to develop crops with enhanced yield and resistance to environmental stresses. Controlling the expression level of OsAP2-39 which includes an APETALA 2 (AP2) domain leads to phenotypic changes in rice. Overexpression of OsAP2-39 leads to a reduction in yield by decreasing the biomass and the number of seeds in the transgenic rice lines. Global transcriptome analysis of the OsAP2-39 overexpression transgenic rice revealed the upregulation of a key abscisic acid (ABA) biosynthetic gene OsNCED-I which codes for 9-cis-epoxycarotenoid dioxygenase and leads to an increase in the endogenous ABA level. In addition to OsNCED-1, the gene expression analysis revealed the upregulation of a gene that codes for the Elongation of Upper most Internode (EUI) protein, an enzyme that catalyzes 16α, 17-epoxidation of non-13-hydroxylated GAs, which has been shown to deactivate gibberellins (GAs) in rice. The exogenous application of GA restores the wild-type phenotype in the transgenic line and ABA application induces the expression of EUI and suppresses the expression of OsAP2-39 in the wild-type line. These observations clarify the antagonistic relationship between ABA and GA and illustrate a mechanism that leads to homeostasis of these hormones. In vivo and in vitro analysis showed that the expression of both OsNCED-1 and EUI are directly controlled by OsAP2-39. Together, these results reveal a novel mechanism for the control of the ABA/GA balance in rice which is regulated by OsAP2-39 that in turn regulates plant growth and seed production.

The APETALA-2-Like Transcription Factor OsAP2-39 Controls Key Interactions between Abscisic Acid and Gibberellin in Rice

PubMed Central

Yaish, Mahmoud W.; El-kereamy, Ashraf; Zhu, Tong; Beatty, Perrin H.; Good, Allen G.; Bi, Yong-Mei; Rothstein, Steven J.

2010-01-01

The interaction between phytohormones is an important mechanism which controls growth and developmental processes in plants. Deciphering these interactions is a crucial step in helping to develop crops with enhanced yield and resistance to environmental stresses. Controlling the expression level of OsAP2-39 which includes an APETALA 2 (AP2) domain leads to phenotypic changes in rice. Overexpression of OsAP2-39 leads to a reduction in yield by decreasing the biomass and the number of seeds in the transgenic rice lines. Global transcriptome analysis of the OsAP2-39 overexpression transgenic rice revealed the upregulation of a key Abscisic Acid (ABA) biosynthetic gene OsNCED-I which codes for 9-cis-epoxycarotenoid dioxygenase and leads to an increase in the endogenous ABA level. In addition to OsNCED-1, the gene expression analysis revealed the upregulation of a gene that codes for the Elongation of Upper most Internode (EUI) protein, an enzyme that catalyzes 16α, 17-epoxidation of non-13-hydroxylated GAs, which has been shown to deactivate gibberellins (GAs) in rice. The exogenous application of GA restores the wild-type phenotype in the transgenic line and ABA application induces the expression of EUI and suppresses the expression of OsAP2-39 in the wild-type line. These observations clarify the antagonistic relationship between ABA and GA and illustrate a mechanism that leads to homeostasis of these hormones. In vivo and in vitro analysis showed that the expression of both OsNCED-1 and EUI are directly controlled by OsAP2-39. Together, these results reveal a novel mechanism for the control of the ABA/GA balance in rice which is regulated by OsAP2-39 that in turn regulates plant growth and seed production. PMID:20838584

Parallel heat transport in reversed shear magnetic field configurations

NASA Astrophysics Data System (ADS)

Blazevski, D.; Del-Castillo-Negrete, D.

2012-03-01

Transport in magnetized plasmas is a key problem in controlled fusion, space plasmas, and astrophysics. Three issues make this problem particularly challenging: (i) The extreme anisotropy between the parallel (i.e., along the magnetic field), χ, and the perpendicular, χ, conductivities (χ/χ may exceed 10^10 in fusion plasmas); (ii) Magnetic field lines chaos; and (iii) Nonlocal parallel transport. We have recently developed a Lagrangian Green's function (LG) method to solve the local and non-local parallel (χ/χ->∞) transport equation applicable to integrable and chaotic magnetic fields. footnotetext D. del-Castillo-Negrete, L. Chac'on, PRL, 106, 195004 (2011); D. del-Castillo-Negrete, L. Chac'on, Phys. Plasmas, APS Invited paper, submitted (2011). The proposed method overcomes many of the difficulties faced by standard finite different methods related to the three issues mentioned above. Here we apply the LG method to study transport in reversed shear configurations. We focus on the following problems: (i) separatrix reconnection of magnetic islands and transport; (ii) robustness of shearless, q'=0, transport barriers; (iii) leaky barriers and shearless Cantori.

Peculiar Traits of Coarse AP (Briefing Charts)

DTIC Science & Technology

2014-12-01

coarse AP Bircumshaw, Newman Active centers are sources of AP decomposition gases AP low temperature decomposition (LTD) Most unstable AP particles ...delay before coarse AP ejection *Coarse AP particle flame retardancy 19 Air Force Research Laboratory Distribution A: Approved for public release...distribution unlimited. PA clearance #. Combustion bomb trials 2 AP phase change may enable coarse particle breakage Fractured coarse AP ejection agrees

The duality of LysU, a catalyst for both Ap4A and Ap3A formation.

PubMed

Wright, Michael; Boonyalai, Nonlawat; Tanner, Julian A; Hindley, Alison D; Miller, Andrew D

2006-08-01

Heat shock inducible lysyl-tRNA synthetase of Escherichia coli (LysU) is known to be a highly efficient diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) synthase. However, we use an ion-exchange HPLC technique to demonstrate that active LysU mixtures actually have a dual catalytic activity, initially producing Ap4A from ATP, before converting that tetraphosphate to a triphosphate. LysU appears to be an effective diadenosine 5',5'''-P1,P3-triphosphate (Ap3A) synthase. Mechanistic investigations reveal that Ap3A formation requires: (a) that the second step of Ap4A formation is slightly reversible, thereby leading to a modest reappearance of adenylate intermediate; and (b) that phosphate is present to trap the intermediate (either as inorganic phosphate, as added ADP, or as ADP generated in situ from inorganic phosphate). Ap3A forms readily from Ap4A in the presence of such phosphate-based adenylate traps (via a 'reverse-trap' mechanism). LysU is also clearly demonstrated to exist in a phosphorylated state that is more physically robust as a catalyst of Ap4A formation than the nonphosphorylated state. However, phosphorylated LysU shows only marginally improved catalytic efficiency. We note that Ap3A effects have barely been studied in prokaryotic organisms. By contrast, there is a body of literature that describes Ap3A and Ap4A having substantially different functions in eukaryotic cells. Our data suggest that Ap3A and Ap4A biosynthesis could be linked together through a single prokaryotic dual 'synthase' enzyme. Therefore, in our view there is a need for new research into the effects and impact of Ap3A alone and the intracellular [Ap3A]/[Ap4A] ratio on prokaryotic organisms.

Theoretical studies on the electronic and optoelectronic properties of [A.2AP(w)/A*.2AP(WC)/C.2AP(w)/C*.2AP(WC)/C.A(w)/C*.A(WC)]-Au8 mismatch nucleobase complexes

NASA Astrophysics Data System (ADS)

Srivastava, Ruby

2018-01-01

The electronic and optoelectronic properties of [A.2AP(w)/A*.2AP(WC)/C.2AP(w)/C*.2AP(WC)/C.A(w)/ C*.A(WC)]-Au8 metal-mismatch nucleobase complexes are investigated by means of density functional theory and time-dependent methods. We selected these mispairs as 2-aminopurine (2AP) produces incorporation errors when binding with cytosine (C) into the wobble (w) C.2AP(w) mispair, and is tautomerised into Watson-Crick (WC)-like base mispair C*.2AP(WC) and less effectively produces A.2AP(w)/A*.2AP(WC) mispairs. The vertical ionisation potential, vertical electron affinity, hardness and electrophilicity index of these complexes have also been discussed. The modifications of energy levels and charge density distributions of the frontier orbitals are also analysed. The absorption spectra of these complexes lie in the visible region, which suggests their application in fluorescent-bio imaging. The mechanism of cooperativity effect is studied by molecular orbital potential (MEP), atoms-in-molecules (AIM) and natural bond orbital analyses. Most metalated pairs have smaller HOMO-LUMO band gaps than the isolated mismatch nucleobases which suggest interesting consequences for electron transfer through DNA duplexes.

SPES-2, an experimental program to support the AP600 development

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

Tarantini, M.; Medich, C.

1995-09-01

In support of the development of the AP600 reactor, ENEA, ENEL, ANSALDO and Westinghouse have signed a research agreement. In the framework of this agreement a complex Full Height Full Pressure (FHFP) integral system testing program has been planned on SPES-2 facility. The main purpose of this paper is to point out the status of the test program; describe the hot per-operational test performed and the complete test matrix, giving all the necessary references on the work already published. Two identical Small Break LOCA transients, performed with Pressurizer to Core Make-up Tank (PRZ-CMT) balance line (Test S00203) and without PRZ-CMTmore » balance line (Test S00303) are then compared, to show how the SPES-2 facility can contribute in confirming the new AP600 reactor design choices and can give useful indications to designers. Although the detailed analysis of test data has not been completed, some consideration on the analytical tools utilized and on the SPES-2 capability to simulate the reference plant is then drawn.« less

AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking

PubMed Central

Setta-Kaffetzi, Niovi; Simpson, Michael A.; Navarini, Alexander A.; Patel, Varsha M.; Lu, Hui-Chun; Allen, Michael H.; Duckworth, Michael; Bachelez, Hervé; Burden, A. David; Choon, Siew-Eng; Griffiths, Christopher E.M.; Kirby, Brian; Kolios, Antonios; Seyger, Marieke M.B.; Prins, Christa; Smahi, Asma; Trembath, Richard C.; Fraternali, Franca; Smith, Catherine H.; Barker, Jonathan N.; Capon, Francesca

2014-01-01

Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis. PMID:24791904

Design, Modeling and Simulations in the RACE Project: Preliminary study for the development of a transport line

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

Maidana, C. O.; Hunt, A. W.; Idaho State University, Department of Physics, PO Box 8106, Pocatello, ID 83209

2007-02-12

As part of the Reactor Accelerator Coupling Experiment (RACE) a set of preliminary studies were conducted to design a transport beam line that could bring a 25 MeV electron beam from a Linear Accelerator to a neutron-producing target inside a subcritical system. Because of the relatively low energy beam, the beam size and a relatively long beam line (implicating a possible divergence problem) different parameters and models were studied before a final design could be submitted for assembly. This report shows the first results obtained from different simulations of the transport line optics and dynamics.

Comparison of expression and enzymatic properties of Aspergillus oryzae lysine aminopeptidases ApsA and ApsB.

PubMed

Marui, Junichiro; Matsushita-Morita, Mayumi; Tada, Sawaki; Hattori, Ryota; Suzuki, Satoshi; Amano, Hitoshi; Ishida, Hiroki; Yamagata, Youhei; Takeuchi, Michio; Kusumoto, Ken-Ichi

2012-08-01

The apsA and apsB genes encoding family M1 aminopeptidases were identified in the industrial fungus Aspergillus oryzae. The apsB was transcriptionally up-regulated up to 2.5-fold in response to the deprivation of nitrogen or carbon sources in growth media, while up-regulation of apsA was less significant. The encoded proteins were bacterially expressed and purified to characterize their enzymatic properties. ApsA and ApsB were optimally active at pH 7.0 and 35 °C and stable at pH ranges of 6-10 and 4-10, respectively, up to 40 °C. The enzymes were inhibited by bestatin and EDTA, as has been reported for family M1 aminopeptidases that characteristically contain a zinc-binding catalytic motif. Both enzymes preferentially liberated N-terminal lysine, which is an essential amino acid and an important additive to animal feed. Enzymes that efficiently release N-terminal lysine from peptides could be useful for food and forage industries. Examination of the reactivity toward peptide substrate of varying length revealed that ApsB exhibited broader substrate specificity than ApsA although the reactivity of ApsB decreased as the length of peptide substrate decreased.

Functions of Adaptor Protein (AP)-3 and AP-1 in Tyrosinase Sorting from Endosomes to MelanosomesD⃞

PubMed Central

Theos, Alexander C.; Tenza, Danièle; Martina, José A.; Hurbain, Ilse; Peden, Andrew A.; Sviderskaya, Elena V.; Stewart, Abigail; Robinson, Margaret S.; Bennett, Dorothy C.; Cutler, Daniel F.; Bonifacino, Juan S.; Marks, Michael S.; Raposo, Graça

2005-01-01

Specialized cells exploit adaptor protein complexes for unique post-Golgi sorting events, providing a unique model system to specify adaptor function. Here, we show that AP-3 and AP-1 function independently in sorting of the melanocyte-specific protein tyrosinase from endosomes to the melanosome, a specialized lysosome-related organelle distinguishable from lysosomes. AP-3 and AP-1 localize in melanocytes primarily to clathrin-coated buds on tubular early endosomes near melanosomes. Both adaptors recognize the tyrosinase dileucine-based melanosome sorting signal, and tyrosinase largely colocalizes with each adaptor on endosomes. In AP-3-deficient melanocytes, tyrosinase accumulates inappropriately in vacuolar and multivesicular endosomes. Nevertheless, a substantial fraction still accumulates on melanosomes, concomitant with increased association with endosomal AP-1. Our data indicate that AP-3 and AP-1 function in partially redundant pathways to transfer tyrosinase from distinct endosomal subdomains to melanosomes and that the AP-3 pathway ensures that tyrosinase averts entrapment on internal membranes of forming multivesicular bodies. PMID:16162817

Size response of an SMPS-APS system to commercial multi-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Lee, Seung-Bok; Lee, Jun-Hyun; Bae, Gwi-Nam

2010-02-01

Carbon nanotubes (CNTs) are representative-engineered nanomaterials with unique properties. The safe production of CNTs urgently requires reliable tools to assess inhalation exposure. In this study, on-line aerosol instruments were employed to detect the release of multi-walled CNTs (MWCNTs) in workplace environments. The size responses of aerosol instruments consisting of both a scanning mobility particle sizer (SMPS) and an aerodynamic particle sizer (APS) were examined using five types of commercial MWCNTs. A MWCNT solution and powder were aerosolized using atomizing and shaking methods, respectively. Regardless of the phase and purity, the aerosolized MWCNTs showed consistent size distributions with both SMPS and APS. The SMPS and APS measurements revealed a dominant broad peak at approximately 200-400 nm and a distinct narrow peak at approximately 2 μm, respectively. Comparing with field application of the two aerosol instruments, the APS response could be a fingerprint of the MWCNTs in a real workplace environment. A modification of the atomizing method is recommended for the long-term inhalation toxicity studies.

Artificial pancreas (AP) clinical trial participants' acceptance of future AP technology.

PubMed

Bevier, Wendy C; Fuller, Serena M; Fuller, Ryan P; Rubin, Richard R; Dassau, Eyal; Doyle, Francis J; Jovanovič, Lois; Zisser, Howard C

2014-09-01

Artificial pancreas (AP) systems are currently an active field of diabetes research. This pilot study examined the attitudes of AP clinical trial participants toward future acceptance of the technology, having gained firsthand experience. After possible influencers of AP technology adoption were considered, a 34-question questionnaire was developed. The survey assessed current treatment satisfaction, dimensions of clinical trial participant motivation, and variables of the technology acceptance model (TAM). Forty-seven subjects were contacted to complete the survey. The reliability of the survey scales was tested using Cronbach's α. The relationship of the factors to the likelihood of AP technology adoption was explored using regression analysis. Thirty-six subjects (76.6%) completed the survey. Of the respondents, 86.1% were either highly likely or likely to adopt the technology once available. Reliability analysis of the survey dimensions revealed good internal consistency, with scores of >0.7 for current treatment satisfaction, convenience (motivation), personal health benefit (motivation), perceived ease of use (TAM), and perceived usefulness (TAM). Linear modeling showed that future acceptance of the AP was significantly associated with TAM and the motivation variables of convenience plus the individual item benefit to others (R(2)=0.26, P=0.05). When insulin pump and continuous glucose monitor use were added, the model significance improved (R(2)=0.37, P=0.02). This pilot study demonstrated that individuals with direct AP technology experience expressed high likelihood of future acceptance. Results support the factors of personal benefit, convenience, perceived usefulness, and perceived ease of use as reliable scales that suggest system adoption in this highly motivated patient population.

Lithium and Isotopic Ratio Li6/Li7 in Magnetic roAp Stars as an Indicator of Active Processes

NASA Astrophysics Data System (ADS)

Polosukhina, N.; Shavrina, A.; Lyashko, D.; Nesvacil, N.; Drake, N.; Smirnova, M.

2015-04-01

The lines of lithium at 6708 Å and 6103 Å are analyzed in high resolution spectra of some sharp-lined and slowly rotating roAp stars. Three spectral synthesis codes— STARSP, ZEEMAN2, and SYNTHM—were used. New lines of rare earth elements (REE) from the DREAM database and the lines calculated on the basis of the NIST energy levels were included. Magnetic splitting and other line broadening processes were taken into account. For both lithium lines, the enhanced abundances of lithium in the atmospheres of the stars studied are obtained. The lithium abundance determined from the Li 6103 Å line is higher than that from the Li 6708 Å for all the stars. This may be evidence of vertical lithium stratification, abnormal temperature distribution, or unidentified blending of the 6103 Å line. Our work on two roAp stars, HD 83368 and HD 60435 (Shavrina et al. 2001) provides evidence of an enhanced lithium abundance near the magnetic-field poles. We can expect similar effects in the sharp-lined roAp stars. High lithium abundance for all the stars and the estimates of the 6Li/7Li ratio (0.2-0.5) can be explained by production of Li in the cosmic ray spallation reactions in the interstellar medium where the stars were born, and by preservation of the original 6Li and 7Li by strong magnetic fields of these stars. The values of the 6Li/7Li ratio expected from production by cosmic rays are about 0.5-0.8 (Knauth et al. 2003; Webber et al. 2002). New laboratory and theoretical gf-values for REE lines are necessary in order to refine our estimates of lithium abundances and the isotopic ratio.

Transepithelial transport of rosuvastatin and effect of ursolic acid on its transport in Caco-2 monolayers.

PubMed

Hua, Wen Jin; Fang, Hu Jin; Hua, Wei Xiao

2012-09-01

The aim of this study was to determine transepithelial transport characteristics of rosuvastatin and effect of ursolic acid (P-gp potential inhibitor) and ko143 (ABC transporters selective inhibitor) on its transport in Caco-2 monolayers. A reliable Caco-2 cell monolayers model was established. The TEER value was used to inspect integrity of cell model. Apparent permeability coefficients (Papp(BL-AP) and Papp(AP-BL)) were used to analyze transepithelial transport of rosuvastatin. Uptake of rosuvastatin was time- and concentration-dependent in Caco-2 cell. The ko143 but not ursolic acid had effect on the uptake of rosuvastatin in Caco-2 cell monolayer model and affected apparent permeability coefficient and apparent permeability of rosuvastatin. Active transport and passive diffusion absorption existed in transepithelial transport of rosuvastatin in Caco-2 cell model. Ursolic acid had no effect on transport of rosuvastatin in Caco-2 cell monolayer. The result indicated that ursolic acid may not cause effect on intestinal absorption of rosuvastatin.

The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family.

PubMed Central

Dreyling, M H; Martinez-Climent, J A; Zheng, M; Mao, J; Rowley, J D; Bohlander, S K

1996-01-01

The translocation t(10;11)(p13;q14) is a recurring chromosomal abnormality that has been observed in patients with acute lymphoblastic leukemia as well as acute myeloid leukemia. We have recently reported that the monocytic cell line U937 has a t(10;11)(p13;q14) translocation. Using a combination of positional cloning and candidate gene approach, we cloned the breakpoint and were able to show that AF10 is fused to a novel gene that we named CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene) located at 11q14. AF10, a putative transcription factor, had recently been cloned as one of the fusion partners of MLL. CALM has a very high homology in its N-terminal third to the murine ap-3 gene which is one of the clathrin assembly proteins. The N-terminal region of ap-3 has been shown to bind to clathrin and to have a high-affinity binding site for phosphoinositols. The identification of the CALM/AF10 fusion gene in the widely used U937 cell line will contribute to our understanding of the malignant phenotype of this line. Images Fig. 1 Fig. 3 PMID:8643484

Erratum: ``A Grid of Non-LTE Line-blanketed Model Atmospheres of O-Type Stars'' (ApJS, 146, 417 [2003])

NASA Astrophysics Data System (ADS)

Lanz, Thierry; Hubeny, Ivan

2003-07-01

We have constructed a comprehensive grid of 680 metal line-blanketed, non-LTE, plane-parallel, hydrostatic model atmospheres for the basic parameters appropriate to O-type stars. The OSTAR2002 grid considers 12 values of effective temperatures, 27,500K<=Teff<=55,000 K with 2500 K steps, eight surface gravities, 3.0<=logg<=4.75 with 0.25 dex steps, and 10 chemical compositions, from metal-rich relative to the Sun to metal-free. The lower limit of logg for a given effective temperature is set by an approximate location of the Eddington limit. The selected chemical compositions have been chosen to cover a number of typical environments of massive stars: the Galactic center, the Magellanic Clouds, blue compact dwarf galaxies like I Zw 18, and galaxies at high redshifts. The paper contains a description of the OSTAR2002 grid and some illustrative examples and comparisons. The complete OSTAR2002 grid is available at our Web site at ApJS, 146, 417 [2003]. Laboratory for Astronomy and Solar Physics, NASA Goddard Space Flight Center, Code 681, Greenbelt, MD 20771.

Thioredoxin reductase regulates AP-1 activity as well as thioredoxin nuclear localization via active cysteines in response to ionizing radiation.

PubMed

Karimpour, Shervin; Lou, Junyang; Lin, Lilie L; Rene, Luis M; Lagunas, Lucio; Ma, Xinrong; Karra, Sreenivasu; Bradbury, C Matthew; Markovina, Stephanie; Goswami, Prabhat C; Spitz, Douglas R; Hirota, Kiichi; Kalvakolanu, Dhananjaya V; Yodoi, Junji; Gius, David

2002-09-12

A recently identified class of signaling factors uses critical cysteine motif(s) that act as redox-sensitive 'sulfhydryl switches' to reversibly modulate specific signal transduction cascades regulating downstream proteins with similar redox-sensitive sites. For example, signaling factors such as redox factor-1 (Ref-1) and transcription factors such as the AP-1 complex both contain redox-sensitive cysteine motifs that regulate activity in response to oxidative stress. The mammalian thioredoxin reductase-1 (TR) is an oxidoreductase selenocysteine-containing flavoprotein that also appears to regulate multiple downstream intracellular redox-sensitive proteins. Since ionizing radiation (IR) induces oxidative stress as well as increases AP-1 DNA-binding activity via the activation of Ref-1, the potential roles of TR and thioredoxin (TRX) in the regulation of AP-1 activity in response to IR were investigated. Permanently transfected cell lines that overexpress wild type TR demonstrated constitutive increases in AP-1 DNA-binding activity as well as AP-1-dependent reporter gene expression, relative to vector control cells. In contrast, permanently transfected cell lines expressing a TR gene with the active site cysteine motif deleted were unable to induce AP-1 activity or reporter gene expression in response to IR. Transient genetic overexpression of either the TR wild type or dominant-negative genes demonstrated similar results using a transient assay system. One mechanism through which TR regulates AP-1 activity appears to involve TRX sub-cellular localization, with no change in the total TRX content of the cell. These results identify a novel function of the TR enzyme as a signaling factor in the regulation of AP-1 activity via a cysteine motif located in the protein.

Copernicus observations of the Ap star Epsilon Ursae Majoris

NASA Technical Reports Server (NTRS)

Mallama, A. D.; Molnar, M. R.

1977-01-01

Spectral scans of the Ap star Epsilon UMa made with the Copernicus satellite show strong line blanketing from profuse Cr II and Fe II lines. In the spectral region covering 1900 to 3000 A, about 500 lines are present which suppress the apparent continuum by at least 15-30%. An accurate line-identification list is compiled showing Eu II present in addition to Mn II and Ni II. The identification of Eu II, however, rests on very stringent identification limits for Fe II. If these are relaxed, the existence of Eu II is dubious. There are no broad features in this spectral region which would suggest strong photoionization discontinuities by metals, but one feature near 2137 A might contain the photoionization edge due to Cr I 5S lying 0.94 eV above the ground level. However, a significant correlation between the line-blanketing strength and the amplitude of the OAO-2 ultraviolet light curves was found such that both monotonically increase in the same proportion toward shorter wavelengths. This gives additional strength to the suggestion that variations in the metal line-blanketing cause the observed photometric variations.

30 Years of APS Congressional Fellows: Looking Back and Looking Forward

NASA Astrophysics Data System (ADS)

2003-04-01

In 1973 AAAS launched a Congressional Fellows Program, and APS was one of three founding participants. Since then, APS has funded one or two Fellows annually to work with a Congressional Committee or on the personal staff of a Member of Congress. These fellows individually and collectively have had and continue to have a large impact in Washington. Six Fellows from different periods of the 30-year program, including a current Member of Congress, will present their views and assessments of the Fellowship program. They will address how it affected them, what it has done for the country and how APS should plan for the future. There will be ample time for questions and discussion. Panelists: Ben Cooper, Association of Oil Pipe Lines (Fellow, 1973-74) Rush Holt, Member, House of Representatives (Fellow, 1982-83) Jane Alexander, Office of Naval Research (Fellow, 1986-87) Duncan Moore, University of Rochester (Fellow, 1993-94) Peter Rooney, House Committee on Science (Fellow, 1997-98) Sherri Stephan, Senate Committee on Government Affairs (Fellow, 2000-01)

AP1S3 mutations are associated with pustular psoriasis and impaired Toll-like receptor 3 trafficking.

PubMed

Setta-Kaffetzi, Niovi; Simpson, Michael A; Navarini, Alexander A; Patel, Varsha M; Lu, Hui-Chun; Allen, Michael H; Duckworth, Michael; Bachelez, Hervé; Burden, A David; Choon, Siew-Eng; Griffiths, Christopher E M; Kirby, Brian; Kolios, Antonios; Seyger, Marieke M B; Prins, Christa; Smahi, Asma; Trembath, Richard C; Fraternali, Franca; Smith, Catherine H; Barker, Jonathan N; Capon, Francesca

2014-05-01

Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Chlamydia trachomatis CT771 (nudH) is an asymmetric Ap4A hydrolase.

PubMed

Barta, Michael L; Lovell, Scott; Sinclair, Amy N; Battaile, Kevin P; Hefty, P Scott

2014-01-14

Asymmetric diadenosine 5',5‴-P(1),P(4)-tetraphosphate (Ap4A) hydrolases are members of the Nudix superfamily that asymmetrically cleave the metabolite Ap4A into ATP and AMP while facilitating homeostasis. The obligate intracellular mammalian pathogen Chlamydia trachomatis possesses a single Nudix family protein, CT771. As pathogens that rely on a host for replication and dissemination typically have one or zero Nudix family proteins, this suggests that CT771 could be critical for chlamydial biology and pathogenesis. We identified orthologues to CT771 within environmental Chlamydiales that share active site residues suggesting a common function. Crystal structures of both apo- and ligand-bound CT771 were determined to 2.6 Å and 1.9 Å resolution, respectively. The structure of CT771 shows a αβα-sandwich motif with many conserved elements lining the putative Nudix active site. Numerous aspects of the ligand-bound CT771 structure mirror those observed in the ligand-bound structure of the Ap4A hydrolase from Caenorhabditis elegans. These structures represent only the second Ap4A hydrolase enzyme member determined from eubacteria and suggest that mammalian and bacterial Ap4A hydrolases might be more similar than previously thought. The aforementioned structural similarities, in tandem with molecular docking, guided the enzymatic characterization of CT771. Together, these studies provide the molecular details for substrate binding and specificity, supporting the analysis that CT771 is an Ap4A hydrolase (nudH).

Pulsation in the presence of a strong magnetic field: the roAp star HD166473

NASA Astrophysics Data System (ADS)

Mathys, G.; Kurtz, D. W.; Elkin, V. G.

2007-09-01

Phase-resolved high-resolution, high signal-to-noise ratio (S/N) observations of the strongly magnetic roAp star HD166473 are analysed. HD166473 was selected as the target of this study because it has one of the strongest magnetic fields of all the roAp stars known with resolved magnetically split lines. Indeed, we show that enhanced pulsation diagnosis can be achieved from consideration of the different pulsation behaviour of the π and σ Zeeman components of the resolved spectral lines. This study is based on a time-series of high spectral resolution observations obtained with the Ultraviolet and Visual Echelle Spectrograph of the Very Large Telescope of the European Southern Observatory. Radial velocity variations due to pulsation are observed in rare earth lines, with amplitudes up to 110ms-1. The variations occur with three frequencies, already detected in photometry, but which can in this work be determined with better precision: 1.833, 1.886 and 1.928mHz. The pulsation amplitudes and phases observed in the rare earth element lines vary with atmospheric height, as is the case in other roAp stars studied in detail. Lines of Fe and of other (mostly non-rare earth) elements do not show any variation to very high precision (1.5ms-1 in the case of Fe). The low amplitudes of the observed variations do not allow the original goal of studying differences between the behaviour of the resolved Zeeman line components to be reached; the S/N achieved in the radial velocity determinations is insufficient to establish definitely the possible existence of such differences. Yet the analysis provides a tantalizing hint at the occurrence of variations of the mean magnetic field modulus with the pulsation frequency, with an amplitude of 21 +/- 5G. Based on observations collected at the European Southern Observatory, Paranal, Chile, as part of programme 067.D-0272. E-mail: gmathys@eso.org

Focused transport of energetic particles along magnetic field lines draped around a coronal mass ejection

NASA Technical Reports Server (NTRS)

Tan, L. C.; Mason, G. M.; Lee, M. A.; Klecker, B.; Ipavich, F. M.

1992-01-01

Evidence is presented for focused transport of energetic particles along magnetic field lines draped around a coronal mass ejection. This evidence was obtained with the University of Maryland/Max-Planck-Institute experiment on the ISEE-3 spacecraft during the decay phase of the June 6, 1979, solar particle event. During the early portion of the decay phase of this event, interplanetary magnetic field lines were apparently draped around a coronal mass ejection, leading to a small focusing length on the western flank where ISEE 3 was located. A period of very slow decrease of particle intensity was observed, along with large sunward anisotropy in the solar wind frame, which is inconsistent with predictions of the standard Fokker-Planck equation models for diffusive transport. It was found possible to fit the observations, assuming that focused transport dominates and that the particle pitch angle scattering is isotropic.

Physico-chemical profiles of the wobble ↔ Watson-Crick G*·2AP(w) ↔ G·2AP(WC) and A·2AP(w) ↔ A*·2AP(WC) tautomerisations: a QM/QTAIM comprehensive survey.

PubMed

Brovarets', Ol'ha O; Voiteshenko, Ivan S; Hovorun, Dmytro M

2017-12-20

This study is intended to clarify in detail the tautomeric transformations of the wobble (w) G*·2AP(w) and A·2AP(w) nucleobase mispairs involving 2-aminopurine (2AP) into the Watson-Crick (WC) G·2AP(WC) and A*·2AP(WC) base mispairs (asterisks denote mutagenic tautomers of the DNA bases), respectively, by quantum-mechanical methods and Bader's Quantum Theory of Atoms in Molecules. Our previously reported methodology has been used, which allows the evolution of the physico-chemical parameters to be tracked along the entire internal reaction coordinate (IRC), not exclusively in the stationary states of these reactions. These biologically important G*·2AP(w) ↔ G·2AP(WC) and A·2AP(w) ↔ A*·2AP(WC) w ↔ WC tautomerisations, which are involved in mutagenic tautomerically-conformational pathways, determine the origin of the transitions and transversions induced by 2AP. In addition, it is established that they proceed through planar, highly stable, zwitterionic transition states and they exhibit similar physico-chemical profiles and stages of sequential intrapair proton transfer, followed by spatial rearrangement of the nucleobases relative to each other within the base pairs. These w ↔ WC tautomerisations occur non-dissociatively and are accompanied by a significant alteration in geometry (from wobble to Watson-Crick and vice versa) and redistribution of the specific intermolecular interactions, which can be divided into 10 patterns including AHB H-bonds and loosened A-H-B covalent bridges along the IRC of tautomerisation. Based on the redistribution of the geometrical and electron-topological parameters of the intrapair hydrogen bonds, exactly 9 key points have been allocated to characterize the evolution of these reactions.

THE ONSITE ON-LINE CALCULATORS AND TRAINING FOR SUBSURFACE CONTAMINANT TRANSPORT SITE ASSESSMENT

EPA Science Inventory

EPA has developed a suite of on-line calculators called "OnSite" for assessing transport of environmental contaminants in the subsurface. The purpose of these calculators is to provide methods and data for common calculations used in assessing impacts from subsurface contaminatio...

Analysis of magnetic activity of the rapidly rotating stars He 373 and AP 225

NASA Astrophysics Data System (ADS)

Kolbin, A. I.; Tsymbal, V. V.

2017-06-01

Spectroscopic and photometric data for the two rapidly rotating members of the α Persei cluster He 373 and AP 225 are analyzed. Improved estimates have been obtained for the projected equatorial rotation velocities: v sin i = 164 km/s for He 323 and v sin i = 129 km/s for AP 225. Multi-band photometric mapping is used to map the spot distributions on the surfaces of the two stars. The fractional spotted areas S and mean temperature difference Δ T between the unspotted photosphere and the spots are estimated ( S = 7% and Δ T = 1000 K for He 373; S = 9% and Δ T = 800 K for AP 225). The H α line profiles of both stars have variable emission components whose widths are used to deduce the presence of extended regions of emission reaching the corotation radius.

Waterborne Transportation Lines of the United States : calendar year 2004. Volume 1 : national summaries

DOT National Transportation Integrated Search

2005-12-15

The annual revision of the Waterborne : Transportation Lines of the United States : (WTLUS) contains summary information of : the vessel companies and their American : flag vessels operating or available for : operation on 31 December 2004 including ...

Metallized solid rocket propellants based on AN/AP and PSAN/AP for access to space

NASA Astrophysics Data System (ADS)

Levi, S.; Signoriello, D.; Gabardi, A.; Molinari, M.; Galfetti, L.; Deluca, L. T.; Cianfanelli, S.; Klyakin, G. F.

2009-09-01

Solid rocket propellants based on dual mixes of inorganic crystalline oxidizers (ammonium nitrate (AN) and ammonium perchlorate (AP)) with binder and a mixture of micrometric-nanometric aluminum were investigated. Ammonium nitrate is a low-cost oxidizer, producing environment friendly combustion products but with lower specific impulse compared to AP. The better performance obtained with AP and the low quantity of toxic emissions obtained by using AN have suggested an interesting compromise based on a dual mixture of the two oxidizers. To improve the thermal response of raw AN, different types of phase stabilized AN (PSAN) and AN/AP co-crystals were investigated.

Operation of the intensity monitors in beam transport lines at Fermilab during Run II¹

DOE PAGES

Crisp, J.; Fellenz, B.; Fitzgerald, J.; ...

2011-10-06

The intensity of charged particle beams at Fermilab must be kept within pre-determined safety and operational envelopes in part by assuring all beam within a few percent has been transported from any source to destination. Beam instensity monitors with toroidial pickups provide such beam intensity measurements in the transport lines between accelerators at FNAL. With Run II, much effort was made to continually improve the resolution and accuracy of the system.

Investigation of Beam Emittance and Beam Transport Line Optics on Polarization

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

Fiedler, Andrew; Syphers, Michael

2017-10-06

Effects of beam emittance, energy spread, optical parameters and magnet misalignment on beam polarization through particle transport systems are investigated. Particular emphasis will be placed on the beam lines being used at Fermilab for the development of the muon beam for the Muon g-2 experiment, including comparisons with the natural polarization resulting from pion decay, and comments on the development of systematic correlations among phase space variables.

AP reclamation and reuse in RSRM propellant

NASA Technical Reports Server (NTRS)

Miks, Kathryn F.; Harris, Stacey A.

1995-01-01

A solid propellant ingredient reclamation pilot plant has been evaluated at the Strategic Operations of Thiokol Corporation, located in Brigham City, Utah. The plant produces AP wet cake (95 percent AP, 5 percent water) for recycling at AP vendors. AP has been obtained from two standard propellant binder systems (PBAN and HTPB). Analytical work conducted at Thiokol indicates that the vendor-recrystallized AP meets Space Shuttle propellant specification requirements. Thiokol has processed 1-, 5-, and 600-gallon propellant mixes with the recrystallized AP. Processing, cast, cure, ballistic, mechanical, and safety properties have been evaluated. Phillips Laboratory static-test-fired 70-pound and 800-pound BATES motors. The data indicate that propellant processed with reclaimed AP has nominal properties.

Choline transport via choline transporter-like protein 1 in conditionally immortalized rat syncytiotrophoblast cell lines TR-TBT.

PubMed

Lee, N-Y; Choi, H-M; Kang, Y-S

2009-04-01

Choline is an essential nutrient for phospholipids and acetylcholine biosynthesis in normal development of fetus. In the present study, we investigated the functional characteristics of choline transport system and inhibitory effect of cationic drugs on choline transport in rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT). Choline transport was weakly Na(+) dependent and significantly influenced by extracellular pH and by membrane depolarization. The transport process of choline is saturable with Michaelis-Menten constants (K(m)) of 68microM and 130microM in TR-TBT 18d-1 and TR-TBT 18d-2 respectively. Choline uptake in the cells was inhibited by unlabeled choline and hemicholinium-3 as well as various organic cations including guanidine, amiloride and acetylcholine. However, the prototypical organic cation tetraethylammonium and cimetidine showed very little inhibitory effect of choline uptake in TR-TBT cells. RT-PCR revealed that choline transporter-like protein 1 (CTL1) and organic cation transporter 2 (OCT2) are expressed in TR-TBT cells. The transport properties of choline in TR-TBT cells were similar or identical to that of CTL1 but not OCT2. CTL1 was also detected in human placenta. In addition, several cationic drugs such as diphenhydramine and verapamil competitively inhibited choline uptake in TR-TBT 18d-1 with K(i) of 115microM and 55microM, respectively. Our results suggest that choline transport system, which has intermediate affinity and weakly Na(+) dependent, in TR-TBT seems to occur through a CTL1 and this system may have relevance with the uptake of pharmacologically important organic cation drugs.

Ectopic expression of Jatropha curcas APETALA1 (JcAP1) caused early flowering in Arabidopsis, but not in Jatropha

PubMed Central

Tang, Mingyong; Tao, Yan-Bin

2016-01-01

Jatropha curcas is a promising feedstock for biofuel production because Jatropha oil is highly suitable for the production of biodiesel and bio-jet fuels. However, Jatropha exhibits a low seed yield as a result of unreliable and poor flowering. APETALA1 (AP1) is a floral meristem and organ identity gene in higher plants. The flower meristem identity genes of Jatropha have not yet been identified or characterized. To better understand the genetic control of flowering in Jatropha, an AP1 homolog (JcAP1) was isolated from Jatropha. An amino acid sequence analysis of JcAP1 revealed a high similarity to the AP1 proteins of other perennial plants. JcAP1 was expressed in inflorescence buds, flower buds, sepals and petals. The highest expression level was observed during the early developmental stage of the flower buds. The overexpression of JcAP1 using the cauliflower mosaic virus (CaMV) 35S promoter resulted in extremely early flowering and abnormal flowers in transgenic Arabidopsis plants. Several flowering genes downstream of AP1 were up-regulated in the JcAP1-overexpressing transgenic plant lines. Furthermore, JcAP1 overexpression rescued the phenotype caused by the Arabidopsis AP1 loss-of-function mutant ap1-11. Therefore, JcAP1 is an ortholog of AtAP1, which plays a similar role in the regulation of flowering in Arabidopsis. However, the overexpression of JcAP1 in Jatropha using the same promoter resulted in little variation in the flowering time and floral organs, indicating that JcAP1 may be insufficient to regulate flowering by itself in Jatropha. This study helps to elucidate the function of JcAP1 and contributes to the understanding of the molecular mechanisms of flower development in Jatropha. PMID:27168978

Transport of Solar Energetic Particles across the Parker field direction due to field line meandering

NASA Astrophysics Data System (ADS)

Laitinen, T. L.; Kopp, A.; Effenberger, F.; Dalla, S.; Marsh, M. S.

2014-12-01

Multi-spacecraft observations of Solar Energetic Particles (SEPs) show that the SEPs can spread large distances across the mean Parker spiral field. The SEPs accelerated during a solar eruption can be observed 360° around the Sun, and the dependence of SEP peak intensity on heliographic longitude at 1 AU has been fitted with Gaussian profiles with σ=30-50° for several events (e.g., Dresing et al 2014; Richardson et al 2014). SEP anisotropy measurements suggest that interplanetary transport is an important factor to the SEP cross-field extent (Dresing et al 2014). However, the currently used diffusive Fokker Planck (FP) description of SEP transport, with realistic diffusion coefficients, has been found insufficient to explain the SEP event cross-field extents. Recently Laitinen et al (2013) emphasised the importance of particle propagation along meandering field lines, which cannot be described as diffusion. They showed that early in an event field line meandering dominates particle cross-field transport and produces events wider than the FP description. They also introduced a new FP model that incorporates both field line meandering and SEP cross-field diffusion using stochastic differential equations and a constant background magnetic field. In this work, we implement the new FP model into Parker field geometry, to study the evolution of an SEP event in the interplanetary space. We compare the new model to the traditional FP approach by using particle and field line diffusion coefficients that are calculated consistently for both models using an assumed radial and spectral description of the turbulence evolution. We find that while the traditional SEP propagation modelling gives typically longitudinal extent with σ=10-20°, the new model results in values σ=30-50°, which is consistent with SEP observations. We conclude that field line meandering must be taken into account when modelling SEP propagation in the interplanetary space.

Molecular and biochemical characterisation of two aspartic proteinases TcAP1 and TcAP2 from Theobroma cacao seeds.

PubMed

Laloi, Maryse; McCarthy, James; Morandi, Olivia; Gysler, Christof; Bucheli, Peter

2002-09-01

Aspartic proteinase (EC 3.4.23) activity plays a pivotal role in the degradation of Theobroma cacao L. seed proteins during the fermentation step of cacao bean processing. Therefore, this enzyme is believed to be critical for the formation of the peptide and amino acid cocoa flavor precursors that occurs during fermentation. Using cDNA cloning and northern blot analysis, we show here that there are at least two distinct aspartic proteinase genes ( TcAP1 and TcAP2) expressed during cacao seed development. Both genes are expressed early during seed development and their mRNA levels decrease towards the end of seed maturation. TcAP2 is expressed at a much higher level than TcAP1, although the expression of TcAP1 increases slightly during germination. The proteins encoded by TcAP1 and TcAP2 are relatively different from each other (73% identity). This, and the fact that the two corresponding genes have different expression patterns, suggests that the TcAP1 and TcAP2 proteins may have different functions in the maturing seeds and during germination. Because the TcAP2 gene is expressed at a much higher level during seed development than TcAP1, it is likely that the TcAP2 protein is primarily responsible for the majority of the industrially important protein hydrolysis that occurs during cacao bean fermentation. Finally, TcAP2 has been functionally expressed in the yeast Yarrowia lipolytica. The secreted recombinant protein is able to hydrolyse bovine haemoglobin at acidic pH and is sensitive to pepstatin A, confirming that TcAP2 encodes an aspartic proteinase, and strongly suggests that this gene encodes the well-characterized aspartic proteinase of mature cacao seeds.

Greenhouse evaluation of Bacillus subtilis AP-01 and Trichoderma harzianum AP-001 in controlling tobacco diseases.

PubMed

Maketon, Monchan; Apisitsantikul, Jirasak; Siriraweekul, Chatchai

2008-04-01

Two biological control agents, Bacillus subtilis AP-01 (Larminar(™)) and Trichoderma harzianum AP-001 (Trisan(™)) alone or/in combination were investigated in controlling three tobacco diseases, including bacterial wilt (Ralstonia solanacearum), damping-off (Pythium aphanidermatum), and frogeye leaf spot (Cercospora nicotiana). Tests were performed in greenhouse by soil sterilization prior to inoculation of the pathogens. Bacterial-wilt and damping off pathogens were drenched first and followed with the biological control agents and for comparison purposes, two chemical fungicides. But for frogeye leaf spot, which is an airborne fungus, a spraying procedure for every treatment including a chemical fungicide was applied instead of drenching. Results showed that neither B. subtilis AP-01 nor T harzianum AP-001 alone could control the bacterial wilt, but when combined, their controlling capabilities were as effective as a chemical treatment. These results were also similar for damping-off disease when used in combination. In addition, the combined B. subtilis AP-01 and T. harzianum AP-001 resulted in a good frogeye leaf spot control, which was not significantly different from the chemical treatment.

Project W-211, initial tank retrieval systems, description of operations for 241-AP-102 and 241-AP-104

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

RIECK, C.A.

1999-02-25

The primary purpose of the Initial Tank Retrieval Systems (ITRS) is to provide systems for retrieval of radioactive wastes stored in underground double-shell tanks (DSTS) for transfer to alternate storage, evaporation, pretreatment or treatment, while concurrently reducing risks associated with safety watch list and other DSTs. This Description of Operations (DOO) defines the control philosophy for the waste retrieval system for tanks 241-AP-102 (AP-102) and 241-AP-104 (AP-104). This DOO will provide a basis for the detailed design of the Retrieval Control System (RCS) for AP-102 and AP-104 and establishes test criteria for the RCS. The test criteria will be usedmore » during qualification testing and acceptance testing to verify operability.« less

Molecular and functional characterization of choline transporter in the human trophoblastic cell line JEG-3 cells.

PubMed

Yara, M; Iwao, B; Hara, N; Yamanaka, T; Uchino, H; Inazu, M

2015-06-01

Choline is essential for the synthesis of the major membrane phospholipid phosphatidylcholine (PC), the methyl donor betaine and the neurotransmitter acetylcholine (ACh), which is involved in several vital biological functions that play key roles in fetal development. In this study, we examined the molecular and functional characteristics of choline uptake in the human trophoblastic cell line JEG-3. We examined [(3)H]choline uptake in the human trophoblastic cell line JEG-3. The expression of CTL1 and CTL2 was evaluated by quantitative real-time PCR, western blotting and immunocytochemistry. We demonstrated that JEG-3 cells take up [(3)H] choline by a saturable process that is mediated by a Na(+)-independent and pH-dependent transport system. The cells have two different [(3)H] choline transport systems, high- and low-affinity, with Km values of 28.4 ± 5.0 μM and 210.6 ± 55.1 μM, respectively. Cationic compounds and hemicholinium-3 (HC-3) inhibited choline uptake. Choline transporter-like protein 1 (CTL1) and CTL2 mRNA and protein were highly expressed in JEG-3 cells and were localized to the plasma membrane. The present results suggest that choline is mainly transported via a high-affinity choline transport system (CTL1) and a low-affinity choline transport system (CTL2) in human trophoblastic JEG-3 cells. These transporters play an important role in the growth of the fetus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Contactless transport of matter in the first five resonance modes of a line-focused acoustic manipulator.

PubMed

Foresti, Daniele; Nabavi, Majid; Poulikakos, Dimos

2012-02-01

The first five resonance modes for transport of matter in a line-focused acoustic levitation system are investigated. Contactless transport was achieved by varying the height between the radiating plate and the reflector. Transport and levitation of droplets in particular involve two limits of the acoustic forces. The lower limit corresponds to the minimum force required to overcome the gravitational force. The upper limit corresponds to the maximum acoustic pressure beyond which atomization of the droplet occurs. As the droplet size increases, the lower limit increases and the upper limit decreases. Therefore to have large droplets levitated, relatively flat radiation pressure amplitude during the translation is needed. In this study, using a finite element model, the Gor'kov potential was calculated for different heights between the reflector and the radiating plate. The application of the Gor'kov potential was extended to study the range of droplet sizes for which the droplets can be levitated and transported without atomization. It was found that the third resonant mode (H(3)-mode) represents the best compromise between high levitation force and smooth pattern transition, and water droplets of millimeter radius can be levitated and transported. The H(3)-mode also allows for three translation lines in parallel. © 2012 Acoustical Society of America

An AP Calculus Classroom Amusement Park

ERIC Educational Resources Information Center

Ferguson, Sarah

2016-01-01

Throughout the school year, AP Calculus teachers strive to teach course content comprehensively and swiftly in an effort to finish all required material before the AP Calculus exam. As early May approaches and the AP Calculus test looms, students and teachers nervously complete lessons, assignments, and assessments to ensure student preparation.…

RISK ASSESSMENT ANALYSES USING EPA'S ON-LINE SITE-SPECIFIC TRANSPORT MODELS AND FIELD DATA

EPA Science Inventory

EPA has developed a suite of on-line calculators and transport models to aid in risk assessment for subsurface contamination. The calculators (www.epa.gov/athens/onsite) provide several levels of tools and data. These include tools for generating commonly-used model input param...

Luteolin, a flavonoid, inhibits AP-1 activation by basophils.

PubMed

Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke; Naka, Tetsuji; Ogata, Atsushi; Shima, Yoshihito; Fujimoto, Minoru; Yamadori, Tomoki; Ohkawara, Tomoharu; Kuwabara, Yusuke; Kawai, Mari; Matsuda, Hisashi; Yoshikawa, Masayuki; Maezaki, Naoyoshi; Tanaka, Tetsuaki; Kawase, Ichiro; Tanaka, Toshio

2006-02-03

Flavonoids including luteolin, apigenin, and fisetin are inhibitors of IL-4 synthesis and CD40 ligand expression by basophils. This study was done to search for compounds with greater inhibitory activity of IL-4 expression and to clarify the molecular mechanisms through which flavonoids inhibit their expression. Of the 37 flavonoids and related compounds examined, ayanin, luteolin, and apigenin were the strongest inhibitors of IL-4 production by purified basophils in response to anti-IgE antibody plus IL-3. Luteolin did not suppress Syk or Lyn phosphorylation in basophils, nor did suppress p54/46 SAPK/JNK, p38 MAPK, and p44/42 MAPK activation by a basophilic cell line, KU812 cells, stimulated with A23187 and PMA. However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells. These results provide a fundamental structure of flavonoids for IL-4 inhibition and demonstrate a novel action of flavonoids that suppresses the activation of AP-1.

Luteolin, a flavonoid, inhibits AP-1 activation by basophils

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

Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke

Flavonoids including luteolin, apigenin, and fisetin are inhibitors of IL-4 synthesis and CD40 ligand expression by basophils. This study was done to search for compounds with greater inhibitory activity of IL-4 expression and to clarify the molecular mechanisms through which flavonoids inhibit their expression. Of the 37 flavonoids and related compounds examined, ayanin, luteolin, and apigenin were the strongest inhibitors of IL-4 production by purified basophils in response to anti-IgE antibody plus IL-3. Luteolin did not suppress Syk or Lyn phosphorylation in basophils, nor did suppress p54/46 SAPK/JNK, p38 MAPK, and p44/42 MAPK activation by a basophilic cell line, KU812more » cells, stimulated with A23187 and PMA. However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells. These results provide a fundamental structure of flavonoids for IL-4 inhibition and demonstrate a novel action of flavonoids that suppresses the activation of AP-1.« less

Advanced APS impacts on vehicle payloads

NASA Technical Reports Server (NTRS)

Schneider, Steven J.; Reed, Brian D.

1989-01-01

Advanced auxiliary propulsion system (APS) technology has the potential to both, increase the payload capability of earth-to-orbit (ETO) vehicles by reducing APS propellant mass, and simplify ground operations and logistics by reducing the number of fluids on the vehicle and eliminating toxic, corrosive propellants. The impact of integrated cryogenic APS on vehicle payloads is addressed. In this system, launch propulsion system residuals are scavenged from integral launch propulsion tanks for use in the APS. Sufficient propellant is preloaded into the APS to return to earth with margin and noncomplete scavenging assumed. No propellant conditioning is required by the APS, but ambient heat soak is accommodated. High temperature rocket materials enable the use of the unconditioned hydrogen/oxygen in the APS and are estimated to give APS rockets specific impulse of up to about 444 sec. The payload benefits are quantified and compared with an uprated monomethylhydrazine/nitrogen tetroxide system in a conservative fashion, by assuming a 25.5 percent weight growth for the hydrogen/oxygen system and a 0 percent weight growth for the uprated system. The combination of scavenging and high performance gives payload impacts which are highly mission specific. A payload benefit of 861 kg (1898 lbm) was estimated for a Space Station Freedom rendezvous mission and 2099 kg (4626 lbm) for a sortie mission, with payload impacts varying with the amount of launch propulsion residual propellants. Missions without liquid propellant scavenging were estimated to have payload penalties, however, operational benefits were still possible.

Advanced APS Impacts on Vehicle Payloads

NASA Technical Reports Server (NTRS)

Schneider, Steven J.; Reed, Brian D.

1989-01-01

Advanced auxiliary propulsion system (APS) technology has the potential to both, increase the payload capability of earth-to-orbit (ETO) vehicles by reducing APS propellant mass, and simplify ground operations and logistics by reducing the number of fluids on the vehicle and eliminating toxic, corrosive propellants. The impact of integrated cryogenic APS on vehicle payloads is addressed. In this system, launch propulsion system residuals are scavenged from integral launch propulsion tanks for use in the APS. Sufficient propellant is preloaded into the APS to return to earth with margin and noncomplete scavenging assumed. No propellant conditioning is required by the APS, but ambient heat soak is accommodated. High temperature rocket materials enable the use of the unconditioned hydrogen/oxygen in the APS and are estimated to give APS rockets specific impulse of up to about 444 sec. The payload benefits are quantified and compared with an uprated monomethyl hydrazine/nitrogen tetroxide system in a conservative fashion, by assuming a 25.5 percent weight growth for the hydrogen/oxygen system and a 0 percent weight growth for the uprated system. The combination and scavenging and high performance gives payload impacts which are highly mission specific. A payload benefit of 861 kg (1898 lbm) was estimated for a Space Station Freedom rendezvous mission and 2099 kg (4626 lbm) for a sortie mission, with payload impacts varying with the amount of launch propulsion residual propellants. Missions without liquid propellant scavenging were estimated to have payload penalties, however, operational benefits were still possible.

Some ethylene biosynthesis and AP2/ERF genes reveal a specific pattern of expression during somatic embryogenesis in Hevea brasiliensis

PubMed Central

2012-01-01

Background Ethylene production and signalling play an important role in somatic embryogenesis, especially for species that are recalcitrant in in vitro culture. The AP2/ERF superfamily has been identified and classified in Hevea brasiliensis. This superfamily includes the ERFs involved in response to ethylene. The relative transcript abundance of ethylene biosynthesis genes and of AP2/ERF genes was analysed during somatic embryogenesis for callus lines with different regeneration potential, in order to identify genes regulated during that process. Results The analysis of relative transcript abundance was carried out by real-time RT-PCR for 142 genes. The transcripts of ERFs from group I, VII and VIII were abundant at all stages of the somatic embryogenesis process. Forty genetic expression markers for callus regeneration capacity were identified. Fourteen markers were found for proliferating calli and 35 markers for calli at the end of the embryogenesis induction phase. Sixteen markers discriminated between normal and abnormal embryos and, lastly, there were 36 markers of conversion into plantlets. A phylogenetic analysis comparing the sequences of the AP2 domains of Hevea and Arabidopsis genes enabled us to predict the function of 13 expression marker genes. Conclusions This first characterization of the AP2/ERF superfamily in Hevea revealed dramatic regulation of the expression of AP2/ERF genes during the somatic embryogenesis process. The gene expression markers of proliferating callus capacity to regenerate plants by somatic embryogenesis should make it possible to predict callus lines suitable to be used for multiplication. Further functional characterization of these markers opens up prospects for discovering specific AP2/ERF functions in the Hevea species for which somatic embryogenesis is difficult. PMID:23268714

VizieR Online Data Catalog: BOSS narrow CIV absorption lines. III. (Chen+, 2016)

NASA Astrophysics Data System (ADS)

Chen, Z.-F.; Gu, Q.-S.; Zhou, L.; Chen, Y.-M.

2018-03-01

In this paper, we extend our previous search of CIV NALs released in Papers I (Chen et al., 2014, Cat. J/ApJS/210/7) and II (Chen et al., 2014, Cat. J/ApJS/215/12) to spectral data redwards of CIV 1549 emission lines. Therefore, the quasar sample and selection criteria are the combination of Papers I (Chen et al., 2014, Cat. J/ApJS/210/7) and II (Chen et al., 2014, Cat. J/ApJS/215/12). (1 data file).

Energy transport in plasmas produced by a high brightness krypton fluoride laser focused to a line

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

Al-Hadithi, Y.; Tallents, G.J.; Zhang, J.

A high brightness krypton fluoride Raman laser (wavelength 0.268 [mu]m) generating 0.3 TW, 12 ps pulses with 20 [mu]rad beam divergence and a prepulse of less than 10[sup [minus]10] has been focused to produce a 10 [mu]m wide line focus (irradiances [similar to]0.8--4[times]10[sup 15] W cm[sup [minus]2]) on plastic targets with a diagnostic sodium fluoride (NaF) layer buried within the target. Axial and lateral transport of energy has been measured by analysis of x-ray images of the line focus and from x-ray spectra emitted by the layer of NaF with varying overlay thicknesses. It is shown that the ratio ofmore » the distance between the critical density surface and the ablation surface to the laser focal width controls lateral transport in a similar manner as for previous spot focus experiments. The measured axial energy transport is compared to MEDUSA [J. P. Christiansen, D. E. T. F. Ashby, and K. V. Roberts, Comput. Phys. Commun. [bold 7], 271 (1974)] one-dimensional hydrodynamic code simulations with an average atom post-processor for predicting spectral line intensities. An energy absorption of [similar to]10% in the code gives agreement with the experimental axial penetration. Various measured line ratios of hydrogen- and helium-like Na and F are investigated as temperature diagnostics in the NaF layer using the RATION [R. W. Lee, B. L. Whitten, and R. E. Strout, J. Quant. Spectrosc. Radiat. Transfer [bold 32], 91 (1984)] code.« less

77 FR 24480 - Application for New Awards; Advanced Placement (AP) Test Fee Program-Reopening the AP Test Fee...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-24

... DEPARTMENT OF EDUCATION Application for New Awards; Advanced Placement (AP) Test Fee Program--Reopening the AP Test Fee Fiscal Year 2012 Competition AGENCY: Office of Elementary and Secondary Education (OESE), Department of Education. ACTION: Notice reopening the AP Test Fee fiscal year 2012 competition...

Structural characterization of the N-terminal mineral modification domains from the molluscan crystal-modulating biomineralization proteins, AP7 and AP24.

PubMed

Wustman, Brandon A; Morse, Daniel E; Evans, John Spencer

2004-08-05

The AP7 and AP24 proteins represent a class of mineral-interaction polypeptides that are found in the aragonite-containing nacre layer of mollusk shell (H. rufescens). These proteins have been shown to preferentially interfere with calcium carbonate mineral growth in vitro. It is believed that both proteins play an important role in aragonite polymorph selection in the mollusk shell. Previously, we demonstrated the 1-30 amino acid (AA) N-terminal sequences of AP7 and AP24 represent mineral interaction/modification domains in both proteins, as evidenced by their ability to frustrate calcium carbonate crystal growth at step edge regions. In this present report, using free N-terminal, C(alpha)-amide "capped" synthetic polypeptides representing the 1-30 AA regions of AP7 (AP7-1 polypeptide) and AP24 (AP24-1 polypeptide) and NMR spectroscopy, we confirm that both N-terminal sequences possess putative Ca (II) interaction polyanionic sequence regions (2 x -DD- in AP7-1, -DDDED- in AP24-1) that are random coil-like in structure. However, with regard to the remaining sequences regions, each polypeptide features unique structural differences. AP7-1 possesses an extended beta-strand or polyproline type II-like structure within the A11-M10, S12-V13, and S28-I27 sequence regions, with the remaining sequence regions adopting a random-coil-like structure, a trait common to other polyelectrolyte mineral-associated polypeptide sequences. Conversely, AP24-1 possesses random coil-like structure within A1-S9 and Q14-N16 sequence regions, and evidence for turn-like, bend, or loop conformation within the G10-N13, Q17-N24, and M29-F30 sequence regions, similar to the structures identified within the putative elastomeric proteins Lustrin A and sea urchin spicule matrix proteins. The similarities and differences in AP7 and AP24 N-terminal domain structure are discussed with regard to joint AP7-AP24 protein modification of calcium carbonate growth. Copyright 2004 Wiley Periodicals, Inc.

HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail

PubMed Central

Roeth, Jeremiah F.; Williams, Maya; Kasper, Matthew R.; Filzen, Tracey M.; Collins, Kathleen L.

2004-01-01

To avoid immune recognition by cytotoxic T lymphocytes (CTLs), human immunodeficiency virus (HIV)-1 Nef disrupts the transport of major histocompatibility complex class I molecules (MHC-I) to the cell surface in HIV-infected T cells. However, the mechanism by which Nef does this is unknown. We report that Nef disrupts MHC-I trafficking by rerouting newly synthesized MHC-I from the trans-Golgi network (TGN) to lysosomal compartments for degradation. The ability of Nef to target MHC-I from the TGN to lysosomes is dependent on expression of the μ1 subunit of adaptor protein (AP) AP-1A, a cellular protein complex implicated in TGN to endolysosomal pathways. We demonstrate that in HIV-infected primary T cells, Nef promotes a physical interaction between endogenous AP-1 and MHC-I. Moreover, we present data that this interaction uses a novel AP-1 binding site that requires amino acids in the MHC-I cytoplasmic tail. In sum, our evidence suggests that binding of AP-1 to the Nef–MHC-I complex is an important step required for inhibition of antigen presentation by HIV. PMID:15569716

Observational studies of roAp stars

NASA Astrophysics Data System (ADS)

Sachkov, M.

2014-11-01

Rapidly oscillating Ap (roAp) stars are high-overtone, low-degree p-mode pulsators that are also chemically peculiar magnetic A stars. Until recently the classical asteroseismic analysis i.e. frequency analysis, of these stars was based on ground and space photometric observations. Significant progress was achieved through access to uninterrupted, ultra-high-precision data from MOST, COROT and Kepler satellites. Over the last ten years the study of roAp stars has been altered drastically from an observational point of view through studies of time-resolved, high-resolution spectra. Their unusual pulsational characteristics, caused by an interplay between the short vertical lengths of the pulsation waves and strong stratification of chemical elements, allow us to examine the upper roAp atmosphere in more detail than is possible for any star except the Sun. In this paper I review the results of recent studies of the pulsations of roAp stars.

Flux variability in the K CA II and H-gamma lines of the AP stars 53 Cam, 41 Tau, Beta CrB, and Alpha(2) CVn

NASA Astrophysics Data System (ADS)

Kuvshinov, V. M.; Plachinda, S. I.

The rapid variability of the relative fluxes in the nuclei of the K Ca II and H-gamma lines of four typical Ap stars, 53 Cam, 41 Tau, Beta CrB, and Alpha(2) CVn, was studied during the period December 1979 - June 1980. Observations were carried out using the scanner-magnetograph of the 2.6-m reflector of the Crimean Astrophysical Observatory. In addition to relative flux variations with the phase of the axial rotation period of the stars, fluctuations of relative fluxes with characteristic times of several minutes to several hours were detected. The upper probability limit for such fluctuations, which are mostly irregular, is estimated at 35 percent for 53 Cam (K Ca II) and 56 percent for Alpha(2) CVn (H-gamma).

The impact of Phase 1 of the Silver Line on the Northern Virginia transportation system.

DOT National Transportation Integrated Search

2017-05-01

The purpose of this study was to assess the impact of Phase 1 of the Washington Metropolitan Area Transit Authoritys Silver Line on the broad regional transportation system, and specifically on the road network operated by the Virginia Department ...

Lattice design and beam dynamics studies of the high energy beam transport line in the RAON heavy ion accelerator

NASA Astrophysics Data System (ADS)

Jin, Hyunchang; Jang, Ji-Ho; Jang, Hyojae; Jeon, Dong-O.

2015-12-01

In RAON heavy ion accelerator, beams generated by superconducting electron cyclotron resonance ion source (ECR-IS) or Isotope Separation On-Line (ISOL) system are accelerated by lower energy superconducting linac and high energy superconducting linac. The accelerated beams are used in the high energy experimental hall which includes bio-medical and muon-SR facilities, after passing through the high energy beam transport lines. At the targets of those two facilities, the stable and small beams meeting the requirements rigorously are required in the transverse plane. Therefore the beams must be safely sent to the targets and simultaneously satisfy the two requirements, the achromatic condition and the mid-plane symmetric condition, of the targets. For this reason, the lattice design of the high energy beam transport lines in which the long deflecting sections are included is considered as a significant issue in the RAON accelerator. In this paper, we will describe the calculated beam optics satisfying the conditions and present the result of particle tracking simulations with the designed lattice of the high energy beam transport lines in the RAON accelerator. Also, the orbit distortion caused by the machine imperfections and the orbit correction with correctors will be discussed.

Drug transporter gene expression in human colorectal tissue and cell lines: modulation with antiretrovirals for microbicide optimization.

PubMed

Mukhopadhya, Indrani; Murray, Graeme I; Berry, Susan; Thomson, John; Frank, Bruce; Gwozdz, Garry; Ekeruche-Makinde, Julia; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

2016-02-01

The objectives of this study were to comprehensively assess mRNA expression of 84 drug transporters in human colorectal biopsies and six representative cell lines, and to investigate the alteration of drug transporter gene expression after exposure to three candidate microbicidal antiretroviral (ARV) drugs (tenofovir, darunavir and dapivirine) in the colorectal epithelium. The outcome of the objectives informs development of optimal ARV-based microbicidal formulations for prevention of HIV-1 infection. Drug transporter mRNA expression was quantified from colorectal biopsies and cell lines by quantitative real-time PCR. Relative mRNA expression was quantified in Caco-2 cells and colorectal explants after induction with ARVs. Data were analysed using Pearson's product moment correlation (r), hierarchical clustering and principal component analysis (PCA). Expression of 58 of the 84 transporters was documented in colorectal biopsies, with genes for CNT2, P-glycoprotein (P-gp) and MRP3 showing the highest expression. No difference was noted between individual subjects when analysed by age, gender or anatomical site (rectum or recto-sigmoid) (r = 0.95-0.99). High expression of P-gp and CNT2 proteins was confirmed by immunohistochemical staining. Similarity between colorectal tissue and cell-line drug transporter gene expression was variable (r = 0.64-0.84). PCA showed distinct clustering of human colorectal biopsy samples, with the Caco-2 cells defined as the best surrogate system. Induction of Caco-2 cell lines with ARV drugs suggests that darunavir-based microbicides incorporating tenofovir may result in drug-drug interactions likely to affect distribution of individual drugs to sub-epithelial target cells. These findings will help optimize complex formulations of rectal microbicides to realize their full potential as an effective approach for pre-exposure prophylaxis against HIV-1 infection. © The Author 2015. Published by Oxford University Press on behalf of the

Forms of selenium affect its transport, uptake and glutathione peroxidase activity in the Caco-2 cell model.

PubMed

Wang, Yanbo; Fu, Linglin

2012-10-01

The experiment was designed to investigate the effect of selenium (Se) chemical forms (sodium selenite, selenium nanoparticle [nano-Se] and selenomethionine) on the transport, uptake and glutathione peroxidase (GSH-Px) activity in the Caco-2 cell model. The transport and uptake of different forms of Se (0.1 μmol l(-1)) across the Caco-2 cell monolayer were carried out in two directions (apical [AP] to basolateral [BL] and BL to AP) for 2 h, respectively, and the apparent permeability coefficient (P(app)), transport efficiency and uptake efficiency were all calculated. In the present study, the transport and uptake of three forms of Se were time-dependent both in AP to BL and BL to AP directions. By the end of 2 h, the transport efficiencies of selenomethionine and nano-Se were higher than that of sodium selenite (P<0.05). The highest uptake efficiency (P<0.05) was observed in cells treated with nano-Se and significant difference (P<0.05) was also observed between the cells incubated with sodium selenite and selenomethionine. As for the P(app), sodium selenite (P<0.05) had the lowest values compared with that of selenomethionine and nano-Se, in both AP-BL and BL-AP. However, no significant differences were observed in GSH-Px activities. These results indicated that the efficiency of Se in the Caco-2 cells varied with its chemical forms, which might be associated with the differences in Se transport and uptake.

Comparative Ballistic Performance of 20mm AP M95 and 20mm AP M75 Projectiles against Rolled Homogeneous Steel Armor

DTIC Science & Technology

1960-05-01

Dominic A. Piccione, " Comparative Ballistic Performanceof 20mm AP M95 and 20mm AP M75 Projectiles againstRolled Homogeneous Steel Armor (U)’\\ WAL-TR-160.1/1... COMPARATIVE BALLISTIC PERFORMANCE OF 20MM AP M95 AND 20MM AP M75 PROJECTILES AGAINST ROLLED HOMOGENEOUS STEEL ARMOR (U) TECHNICAL REPORT NO. WAL TR I60.l/I(c...o > -< Abt9sortf bl O *_, o o -o WATERTOWN ARSENAL LABORATORIES co COMPARATIVE BALLISTIC PERFORMANCE OF 20MM AP M95 AND 20MM AP M75

Transportation Lines on the Atlantic, Gulf, and Pacific Coasts, Transportation Series 5, 1980.

DTIC Science & Technology

1982-05-01

DIP?. 6OU009. r11 77611 7 61117 79*9290 * 79*9lP, CO. 7.O 05ll PkIIP63&, PA. t,10133 6111 CA199A M ARINIPLI0NM P el . I. M INC. NIIOP9 L0f.0 P ulf" few...iUAVA4mI LA ’UlO oIlO Ol696 S PAIN~, 4 6.. 14AR146 to ROSY TOK 4 0 *3 RA C84 ? tlO go.. INC. 1106AO6d t05m. 4lls 3 spl1olEs Ulm TRANSP64? ORO M T Fr AVlNU...BrA44 69D1164 CO . I IllF TwoI IT.?4 I OALfln, El . ile 0’-- -- 1% XXVIII TABLE 1-ALPHABETICAL LIST OF TRANSPORTATION LINES 5 OPERATOR NIE ADORES 9

APS Education and Diversity Efforts

NASA Astrophysics Data System (ADS)

Prestridge, Katherine; Hodapp, Theodore

2015-11-01

American Physical Society (APS) has a wide range of education and diversity programs and activities, including programs that improve physics education, increase diversity, provide outreach to the public, and impact public policy. We present the latest programs spearheaded by the Committee on the Status of Women in Physics (CSWP), with highlights from other diversity and education efforts. The CSWP is working to increase the fraction of women in physics, understand and implement solutions for gender-specific issues, enhance professional development opportunities for women in physics, and remedy issues that impact gender inequality in physics. The Conferences for Undergraduate Women in Physics, Professional Skills Development Workshops, and our new Professional Skills program for students and postdocs are all working towards meeting these goals. The CSWP also has site visit and conversation visit programs, where department chairs request that the APS assess the climate for women in their departments or facilitate climate discussions. APS also has two significant programs to increase participation by underrepresented minorities (URM). The newest program, the APS National Mentoring Community, is working to provide mentoring to URM undergraduates, and the APS Bridge Program is an established effort that is dramatically increasing the number of URM PhDs in physics.

Ap4A induces apoptosis in human cultured cells.

PubMed

Vartanian, A; Alexandrov, I; Prudowski, I; McLennan, A; Kisselev, L

1999-07-30

Diadenosine oligophosphates (Ap(n)A) have been proposed as intracellular and extracellular signaling molecules in animal cells. The ratio of diadenosine 5',5'''-P1,P3-triphosphate to diadenosine 5',5'''-P1,P4-tetraphosphate (Ap3A/Ap4A) is sensitive to the cellular status and alters when cultured cells undergo differentiation or are treated with interferons. In cells undergoing apoptosis induced by DNA topoisomerase II inhibitor VP16, the concentration of Ap3A decreases significantly while that of Ap4A increases. Here, we have examined the effects of exogenously added Ap3A and Ap4A on apoptosis and morphological differentiation. Penetration of Ap(n)A into cells was achieved by cold shock. Ap4A at 10 microM induced programmed cell death in human HL60, U937 and Jurkat cells and mouse VMRO cells and this effect appeared to require Ap4A breakdown as hydrolysis-resistant analogues of Ap4A were inactive. On its own, Ap3A induced neither apoptosis nor cell differentiation but did display strong synergism with the protein kinase C activators 12-deoxyphorbol-13-O-phenylacetate and 12-deoxyphorbol-13-O-phenylacetate-20-acetate in inducing differentiation of HL60 cells. We propose that Ap4A and Ap3A are physiological antagonists in determination of the cellular status: Ap4A induces apoptosis whereas Ap3A is a co-inductor of differentiation. In both cases, the mechanism of signal transduction remains unknown.

Line transport in turbulent atmosphere

NASA Astrophysics Data System (ADS)

Nikoghossian, Artur

We consider the spectral line transfer in turbulent atmospheres with a spatially correlated velocity field. Both the finite and semi-infinite media are treated. In finding the observed intensities we first deal with the problem for determining the mean intensity of radiation emerging from the medium for a fixed value of turbulent velocity at its boundary. New approach proposed in solving this problem is based on invariant imbedding technique which yields the solution of the proper problems for a family of media of different optical thicknesses and allows tackling different kinds of inhomogeneous problems. The dependence of the line profile, integral intensity and the line width on the mean correlation length and average value of the hydrodynamic velocity is studied. It is shown that the transition from a micro-turbulent regime to a macro-turbulent one occurs within a comparatively narrow range of variation in the correlation length. The diffuse reflection of the line radiation from a one-dimensional semi-infinite turbulent atmosphere is examined. In addition to the observed spectral line profile, statistical averages describing the diffusion process in the atmosphere (mean number of scattering events, average time spent by a diffusing photon in the medium) are determined. The dependence of these quantities on the average hydrodynamic velocity and correlation coefficient is studied.

Study of Pulsations in the Atmosphere of the roAp star HD 137949

NASA Astrophysics Data System (ADS)

Sachkov, M.; Hareter, M.; Ryabchikova, T.; Wade, G.; Kochukhov, O.; Weiss, W. W.

The roAp star HD 137949 (33 Lib) shows the most complex pulsational behaviour among all roAp stars. Mkrtichian et al. (2003) found nearly anti-phase pulsations of Nd II and Nd III lines, which they attribute to the presence of a pulsation node high in the atmosphere of HD 137949. This was confirmed by Kurtz at al. (2005), who also find that in some REE lines the main frequency, corresponding to 8.27 min, and its harmonic have almost equal RV amplitudes. Based on high accuracy observations Ryabchikova et al. (2007a) studied pulsational characteristics of the HD 137949 atmosphere in detail. In general, spectroscopy provides 3D resolution of modes and allows to search for the photometrically undetectable frequencies. The high-accuracy space photometry provides very high-precision measurements of detected pulsation frequencies and enables an accurate phasing of multi-site spectroscopic data. A combination of simultaneous spectroscopy and photometry represents the most sophisticated asteroseismic dataset for any roAp star. In 2009 the star HD 137949 became a target of an intense observing campaign that combined ground-based spectroscopy with space photometry, obtained with the MOST satellite. We collected 780 spectra using the ESPaDOnS spectrograph mounted on the 3.6 m CFHT telescope; 374 spectra were obtained with the FIES spectrograph mounted on the 2.56-m NOT to perform the time-resolved spectroscopy of HD 137949. In addition, we used 111 UVES spectra (2004) from the ESO archive to check the mode stability. The frequency analysis of the new radial velocity (RV) measurements confirmed the previously reported frequency pattern (two frequencies and the first harmonic of the main frequency), and revealed an additional frequency at 1.991 mHz. The new frequency solution fits perfectly the RV variations from the 2004 and 2009 observational sets providing a strong support for the p-mode stability in the roAp star HD 137949 for at least 5 years.

On-line atomic data access

NASA Astrophysics Data System (ADS)

Schultz, David R.; Nash, Jeffrey K.

1996-07-01

The need for atomic data is one which continues to expand in a wide variety of applications including fusion energy, astrophysics, laser-produced plasma research, and plasma processing. Modern computer database and communications technology enables this data to be placed on-line and obtained by users over the INTERNET. Presented here is a summary of the observations and conclusions regarding such on-line atomic data access derived from a forum held at the Tenth APS Topical Conference on Atomic Processes in Plasmas.

Functional Coding Variation in Recombinant Inbred Mouse Lines Reveals Novel Serotonin Transporter-Associated Phenotypes

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

Carneiro, Ana; Airey, David; Thompson, Brent

The human serotonin (5-hydroxytryptamine, 5-HT) transporter (hSERT, SLC6A4) figures prominently in the etiology or treatment of many prevalent neurobehavioral disorders including anxiety, alcoholism, depression, autism and obsessive-compulsive disorder (OCD). Here we utilize naturally occurring polymorphisms in recombinant inbred (RI) lines to identify novel phenotypes associated with altered SERT function. The widely used mouse strain C57BL/6J, harbors a SERT haplotype defined by two nonsynonymous coding variants (Gly39 and Lys152 (GK)). At these positions, many other mouse lines, including DBA/2J, encode Glu39 and Arg152 (ER haplotype), assignments found also in hSERT. Synaptosomal 5-HT transport studies revealed reduced uptake associated with the GKmore » variant. Heterologous expression studies confirmed a reduced SERT turnover rate for the GK variant. Experimental and in silico approaches using RI lines (C57Bl/6J X DBA/2J=BXD) identifies multiple anatomical, biochemical and behavioral phenotypes specifically impacted by GK/ER variation. Among our findings are multiple traits associated with anxiety and alcohol consumption, as well as of the control of dopamine (DA) signaling. Further bioinformatic analysis of BXD phenotypes, combined with biochemical evaluation of SERT knockout mice, nominates SERT-dependent 5-HT signaling as a major determinant of midbrain iron homeostasis that, in turn, dictates ironregulated DA phenotypes. Our studies provide a novel example of the power of coordinated in vitro, in vivo and in silico approaches using murine RI lines to elucidate and quantify the system-level impact of gene variation.« less

Mechanisms of cellular uptake, intracellular transportation, and degradation of CIGB-300, a Tat-conjugated peptide, in tumor cell lines.

PubMed

Benavent Acero, Fernando R; Perera Negrin, Yasser; Alonso, Daniel F; Perea, Silvio E; Gomez, Daniel E; Farina, Hernán G

2014-06-02

CIGB-300 is a cyclic synthetic peptide that induces apoptosis in malignant cells, elicits antitumor activity in cancer animal models, and shows tumor reduction signs when assayed in first-in-human phase I trial in patients with cervical tumors. CIGB-300 impairs phosphorylation by casein kinase 2 through targeting the substrate's phosphoacceptor domain. CIGB-300 was linked to the cell penetrating peptide Tat to facilitate the delivery into cells. Previously, we showed that CIGB-300 had a differential antiproliferative behavior in different tumor cell lines. In this work, we studied differential antiproliferative behavior in terms of cellular uptake, intracellular transportation, and degradation in tumor cell lines with dissimilar sensitivity to CIGB-300. The internalization of CIGB-300 was studied in different malignant cell lines. We found that the cell membrane heparan sulfate proteoglycans act as main receptors for extracellular CIGB-300 uptake. The most sensitive tumor cell lines showed higher intracellular incorporation of CIGB-300 in comparison to less sensitive cell lines. Furthermore, CIGB-300 uptake is time- and concentration-dependent in all studied cell lines. It was shown that CIGB-300 has the ability to penetrate cells mainly by direct membrane translocation. However, a minor proportion of the peptide uses an energy-dependent endocytic pathway mechanism to gain access into cells. CIGB-300 is internalized and transported into cells preferentially by caveolae-mediated endocytosis. Lysosomes are involved in CIGB-300 degradation; highly sensitive cell lines showed degradation at earlier times compared to low sensitive cells. Altogether, our data suggests a mechanism of internalization, vesicular transportation, and degradation for CIGB-300 in tumor cells.

Line Transport in Turbulent Atmospheres

NASA Astrophysics Data System (ADS)

Nikoghossian, A. G.

2017-07-01

The spectral line transfer in turbulent atmospheres with a spatially correlated velocity field is examined. Both the finite and semi-infinite media are treated. In finding the observed intensities we first deal with the problem for determining the mean intensity of radiation emerging from the medium for a fixed value of turbulent velocity at its boundary. A new approach proposed for solving this problem is based on the invariant imbedding technique which yields the solution of the proper problems for a family of media of different optical thicknesses and allows tackling different kinds of inhomogeneous problems. The dependence of the line profile, integral intensity, and the line width on the mean correlation length and the average value of the hydrodynamic velocity is studied. It is shown that the transition from a micro-turbulent regime to a macro-turbulence occurs within a comparatively narrow range of variation in the correlation length . Ambartsumian's principle of invariance is used to solve the problem of diffuse reflection of the line radiation from a one-dimensional semi-infinite turbulent atmosphere. In addition to the observed spectral line profile, statistical averages describing the diffusion process in the atmosphere (mean number of scattering events, average time spent by a diffusing photon in the medium) are determined. The dependence of these quantities on the average hydrodynamic velocity and correlation coefficient is studied.

APS Conference on Understanding the Biological Clock: From Genetics to Physiology

NASA Technical Reports Server (NTRS)

Frank, Martin

1996-01-01

The Conference was designed to take advantage of the fusion of two intellectually dominant but heretofore separate lines of clock research, vertebrate physiology and invertebrate and microbial genetics. The APS Conference attracted 251 scientists, 68 of whom were students. In addition to the excellent speaker program organized by Dunlap and Loros, the attendees also submitted 93 volunteer abstracts that were programmed in poster sessions. Thirty-four percent of the submitted abstracts were first authorized by a female student or scientist.

Transepithelial transport of flavanone in intestinal Caco-2 cell monolayers

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

Kobayashi, Shoko; Konishi, Yutaka

2008-03-28

Our recent study [S. Kobayashi, S. Tanabe, M. Sugiyama, Y. Konishi, Transepithelial transport of hesperetin and hesperidin in intestinal Caco-2 cell monolayers, Biochim. Biophys. Acta, 1778 (2008) 33-41] shows that the mechanism of absorption of hesperetin involves both proton-coupled active transport and transcellular passive diffusion. Here, as well as analyzing the cell permeability of hesperetin, we also study the transport of other flavanones, naringenin and eriodictyol, using Caco-2 cell monolayers. Similar to hesperetin mentioned, naringenin and eriodictyol showed proton-coupled polarized transport in apical-to-basolateral direction in non-saturable manner, constant permeation in the apical-to-basolateral direction (J{sub ap{yields}}{sub bl}) irrespective of the transepithelialmore » electrical resistance (TER), and preferable distribution into the basolateral side after apical loading in the presence of a proton gradient. Furthermore, the proton-coupled J{sub ap{yields}}{sub bl} of hesperetin, naringenin and eriodictyol, were inhibited by substrates of the monocarboxylic acid transporter (MCT), such as benzoic acid, but not by ferulic acid. In contrast, both benzoic and ferulic acids have no stimulatory effect on J{sub ap{yields}}{sub bl} of each flavanone by trans-stimulation analysis. These results indicates that proton-driven active transport is commonly participated in the absorption of flavanone in general, and that its transport is presumed to be unique other than MCT-mediated transport for absorption of phenolic acids (PAs), sodium-dependent MCT (SMCT) nor anion exchanger-mediated transport.« less

A Novel GLP1 Receptor Interacting Protein ATP6ap2 Regulates Insulin Secretion in Pancreatic Beta Cells*

PubMed Central

Dai, Feihan F.; Bhattacharjee, Alpana; Liu, Ying; Batchuluun, Battsetseg; Zhang, Ming; Wang, Xinye Serena; Huang, Xinyi; Luu, Lemieux; Zhu, Dan; Gaisano, Herbert; Wheeler, Michael B.

2015-01-01

GLP1 activates its receptor, GLP1R, to enhance insulin secretion. The activation and transduction of GLP1R requires complex interactions with a host of accessory proteins, most of which remain largely unknown. In this study, we used membrane-based split ubiquitin yeast two-hybrid assays to identify novel GLP1R interactors in both mouse and human islets. Among these, ATP6ap2 (ATPase H+-transporting lysosomal accessory protein 2) was identified in both mouse and human islet screens. ATP6ap2 was shown to be abundant in islets including both alpha and beta cells. When GLP1R and ATP6ap2 were co-expressed in beta cells, GLP1R was shown to directly interact with ATP6ap2, as assessed by co-immunoprecipitation. In INS-1 cells, overexpression of ATP6ap2 did not affect insulin secretion; however, siRNA knockdown decreased both glucose-stimulated and GLP1-induced insulin secretion. Decreases in GLP1-induced insulin secretion were accompanied by attenuated GLP1 stimulated cAMP accumulation. Because ATP6ap2 is a subunit required for V-ATPase assembly of insulin granules, it has been reported to be involved in granule acidification. In accordance with this, we observed impaired insulin granule acidification upon ATP6ap2 knockdown but paradoxically increased proinsulin secretion. Importantly, as a GLP1R interactor, ATP6ap2 was required for GLP1-induced Ca2+ influx, in part explaining decreased insulin secretion in ATP6ap2 knockdown cells. Taken together, our findings identify a group of proteins that interact with the GLP1R. We further show that one interactor, ATP6ap2, plays a novel dual role in beta cells, modulating both GLP1R signaling and insulin processing to affect insulin secretion. PMID:26272612

AP1 binding site is another target of FGF2 regulation of bone sialoprotein gene transcription.

PubMed

Takai, Hideki; Araki, Shouta; Mezawa, Masaru; Kim, Dong-Soon; Li, Xinyue; Yang, Li; Li, Zhengyang; Wang, Zhitao; Nakayama, Youhei; Ogata, Yorimasa

2008-02-29

Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. We previously reported that fibroblast growth factor 2 (FGF2) regulates BSP gene transcription via FGF2 response element (FRE) in the proximal promoter of rat BSP gene. We here report that activator protein 1 (AP1) binding site overlapping with glucocorticoid response element (GRE) AP1/GRE in the rat BSP gene promoter is another target of FGF2. Using the osteoblastic cell line ROS17/2.8, we determined that BSP mRNA levels increased by 10 ng/ml FGF2 at 6 and 12 h. Runx2 protein levels increased by FGF2 (10 ng/ml) at 3 h. Treatment of ROS17/2.8 cells with FGF2 (10 ng/ml, 12 h) increased luciferase activities of constructs including -116 to +60 and -938 to +60 of the rat BSP gene promoter. Effects of FGF2 abrogated in constructs included 2 bp mutations in the FRE and AP1/GRE elements. Luciferase activities induced by FGF2 were blocked by tyrosine kinase inhibitor herbimycin A, src-tyrosine kinase inhibitor PP1 and MAP kinase kinase inhibitor U0126. Gel shift analyses showed that FGF2 increased binding of FRE and AP1/GRE elements. Notably, the AP1/GRE-protein complexes were supershifted by Smad1 and c-Fos antibodies, c-Jun and Dlx5 antibodies disrupted the complexes formation, on the other hand AP1/GRE-protein complexes did not change by Runx2 antibody. These studies demonstrate that FGF2 stimulates BSP gene transcription by targeting the FRE and AP1/GRE elements in the rat BSP gene promoter.

Validation of the new trapped environment AE9/AP9/SPM at low Earth orbit

NASA Astrophysics Data System (ADS)

Badavi, Francis F.

2014-09-01

The completion of the international space station (ISS) in 2011 has provided the space research community an ideal proving ground for future long duration human activities in space. Ionizing radiation measurements in ISS form the ideal tool for the validation of radiation environmental models, nuclear transport codes and nuclear reaction cross sections. Indeed, prior measurements on the space transportation system (STS; shuttle) provided vital information impacting both the environmental models and the nuclear transport code developments by indicating the need for an improved dynamic model of the low Earth orbit (LEO) trapped environment. Additional studies using thermo-luminescent detector (TLD), tissue equivalent proportional counter (TEPC) area monitors, and computer aided design (CAD) model of earlier ISS configurations, confirmed STS observations that, as input, computational dosimetry requires an environmental model with dynamic and directional (anisotropic) behavior, as well as an accurate six degree of freedom (DOF) definition of the vehicle attitude and orientation along the orbit of ISS. At LEO, a vehicle encounters exposure from trapped particles and attenuated galactic cosmic rays (GCR). Within the trapped field, a challenge arises from properly estimating the amount of exposure acquired. There exist a number of models to define the intensities of the trapped particles during the solar quiet and active times. At active times, solar energetic particles (SEP) generated by solar flare or coronal mass ejection (CME) also contribute to the exposure at high northern and southern latitudes. Among the more established trapped models are the historic and popular AE8/AP8, dating back to the 1980s, the historic and less popular CRRES electron/proton, dating back to 1990s and the recently released AE9/AP9/SPM. The AE9/AP9/SPM model is a major improvement over the older AE8/AP8 and CRRES models. This model is derived from numerous measurements acquired over four

Accumulation of True Single Strand Breaks and AP sites in Base Excision Repair Deficient Cells

PubMed Central

Luke, April M.; Chastain, Paul D.; Pachkowski, Brian F.; Afonin, Valeriy; Takeda, Shunichi; Kaufman, David G.; Swenberg, James A.; Nakamura, Jun

2010-01-01

Single strand breaks (SSBs) are one of the most frequent DNA lesions caused by endogenous and exogenous agents. The most utilized alkaline-based assays for SSB detection frequently give false positive results due to the presence of alkali-labile sites that are converted to SSBs. Methoxyamine, an acidic O-hydroxylamine, has been utilized to measure DNA damage in cells. However, the neutralization of methoxyamine is required prior to usage. Here we developed a convenient, specific SSB assay using alkaline gel electrophoresis (AGE) coupled with a neutral O-hydroxylamine, O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (OTX). OTX stabilizes abasic sites (AP sites) to prevent their alkaline incision while still allowing for strong alkaline DNA denaturation. DNA from DT40 and isogenic polymerase β null cells exposed to methyl methanesulfonate were applied to the OTX-coupled AGE (OTX-AGE) assay. Time-dependent increases in SSBs were detected in each cell line with more extensive SSB formation in the null cells. These findings were supported by an assay that indirectly detects SSBs through measuring NAD(P)H depletion. An ARP-slot blot assay demonstrated a significant time-dependent increase in AP sites in both cell lines by 1 mM MMS compared to control. Furthermore, the Pol β-null cells displayed greater AP site formation than the parental DT40 cells. OTX use represents a facile approach for assessing SSB formation, whose benefits can also be applied to other established SSB assays. PMID:20851134

Functional Characterization of a Vesicular Glutamate Transporter in an Interneuron That Makes Excitatory and Inhibitory Synaptic Connections in a Molluscan Neural Circuit

PubMed Central

Alexeeva, Vera; Chen, Song-an; Yu, Ke; Due, Michael R.; Tan, Li-nuo; Chen, Ting-ting; Liu, Dan-dan; Cropper, Elizabeth C.; Vilim, Ferdinand S.; Weiss, Klaudiusz R.

2015-01-01

Understanding circuit function requires the characterization of component neurons and their neurotransmitters. Previous work on radula protraction in the Aplysia feeding circuit demonstrated that critical neurons initiate feeding via cholinergic excitation. In contrast, it is less clear how retraction is mediated at the interneuronal level. In particular, glutamate involvement was suggested, but was not directly confirmed. Here we study a suspected glutamatergic retraction interneuron, B64. We used the representational difference analysis (RDA) method to successfully clone an Aplysia vesicular glutamate transporter (ApVGLUT) from B64 and from a glutamatergic motor neuron B38. Previously, RDA was used to characterize novel neuropeptides. Here we demonstrate its utility for characterizing other types of molecules. Bioinformatics suggests that ApVGLUT is more closely related to mammalian VGLUTs than to Drosophila and Caenorhabditis elegans VGLUTs. We expressed ApVGLUT in a cell line, and demonstrated that it indeed transports glutamate in an ATP and proton gradient-dependent manner. We mapped the ApVGLUT distribution in the CNS using in situ hybridization and immunocytochemistry. Further, we demonstrated that B64 is ApVGLUT positive, supporting the idea that it is glutamatergic. Although glutamate is primarily an excitatory transmitter in the mammalian CNS, B64 elicits inhibitory PSPs in protraction neurons to terminate protraction and excitatory PSPs in retraction neurons to maintain retraction. Pharmacological data indicated that both types of PSPs are mediated by glutamate. Thus, glutamate mediates the dual function of B64 in Aplysia. More generally, our systematic approaches based on RDA may facilitate analyses of transmitter actions in small circuits with identifiable neurons. PMID:26085636

A demonstration of a transportable radio interferometric surveying system with 3-cm accuracy on a 307-m base line

NASA Technical Reports Server (NTRS)

Ong, K. M.; Macdoran, P. F.; Thomas, J. B.; Fliegel, H. F.; Skjerve, L. J.; Spitzmesser, D. J.; Batelaan, P. D.; Paine, S. R.; Newsted, M. G.

1976-01-01

A precision geodetic measurement system (Aries, for Astronomical Radio Interferometric Earth Surveying) based on the technique of very long base line interferometry has been designed and implemented through the use of a 9-m transportable antenna and the NASA 64-m antenna of the Deep Space Communications Complex at Goldstone, California. A series of experiments designed to demonstrate the inherent accuracy of a transportable interferometer was performed on a 307-m base line during the period from December 1973 to June 1974. This short base line was chosen in order to obtain a comparison with a conventional survey with a few-centimeter accuracy and to minimize Aries errors due to transmission media effects, source locations, and earth orientation parameters. The base-line vector derived from a weighted average of the measurements, representing approximately 24 h of data, possessed a formal uncertainty of about 3 cm in all components. This average interferometry base-line vector was in good agreement with the conventional survey vector within the statistical range allowed by the combined uncertainties (3-4 cm) of the two techniques.

High concentrations of intracellular Ap4A and/or Ap5A in developing Myxococcus xanthus cells inhibit sporulation.

PubMed

Kimura, Yoshio; Tanaka, Chihiro; Sasaki, Katsuho; Sasaki, Masashi

2017-01-01

Diadenosine polyphosphates (ApnA) are thought to act as signalling molecules regulating stress responses and biofilm formation in prokaryotes. However, ApnA function in Myxococcus xanthus remains unknown. Here, we investigated the role of ApnA in M. xanthus, using the wild-type and ApnA hydrolase (apaH) mutant strains exposed to various stress conditions. In both wild-type and apaH mutant cells cultured on starvation medium (CF agar), the levels of intracellular diadenosine tetraphosphate (Ap4A) and pentaphosphate (Ap5A) increased several fold during the first 16 h of development and decreased gradually thereafter. The levels of Ap4A and Ap5A in the apaH mutant were about 5- and 11-fold higher than those in the wild-type strain at 16 h, respectively. ApnA hydrolase activity of the wild-type strain increased 1.5-fold during the first 8 h of development, and it then gradually decreased. The apaH mutant formed spores 1-2 days after the wild-type strain did, and the yield of viable spores was 5.5 % of that in the wild-type strain 5 days after inoculation onto CF agar. These results suggest the possibility that high intracellular levels of Ap4A and/or Ap5A may inhibit M. xanthus sporulation at the early stage of development and that the bacteria reduce intracellular Ap4A and Ap5A accumulation through ApnA hydrolase activity.

Comparison of Spectral and Scintillation Properties of LuAP:Ce and LuAP:Ce,Sc Single Crystals

NASA Astrophysics Data System (ADS)

Petrosyan, Ashot G.; Derdzyan, Marina; Ovanesyan, Karine; Shirinyan, Grigori; Lecoq, Paul; Auffray, Etiennette; Kronberger, Matthias; Frisch, Benjamin; Pedrini, Christian; Dujardin, Christophe

2009-10-01

Scintillation properties of LuAP:Ce and LuAP:Ce,Sc crystal series were studied under excitation by gamma-rays from a 137Cs source. Both series demonstrated comparable optical quality in terms of underlying absorption at 260 nm, slope of the optical edge and transmission in the range of emission. The light yield of LuAP:Ce crystals measured in 0.2 cm times 0.2 cm times 0.8 cm pixels increases linearly with the Ce concentration reaching at 0.58 at. % 6448 plusmn 322 ph/MeV and 9911 plusmn 496 ph/MeV in the long and in the short directions respectively (the light yield ratio is 65%) and shows no sign of light saturation. The energy resolution is found to depend, among other factors, on the uniformity of Ce concentration within the pixels and is improved to 7.1 plusmn 0.4% (I = 0.2 cm), 9.5 plusmn 0.5% (I = 0.8 cm). Intentional co-doping with Sc + ions was tested and resulted in increase of the Ce distribution coefficient to about 0.3. This enabled to increase the concentration of Ce in LuAP:Ce,Sc crystals up to 0.7 at. %, while conserving high optical quality. In contrast to LuAP:Ce, the light yield in LuAP:Ce,Sc crystals does not increase with Ce concentration, the photo peak being gradually suppressed. The involved mechanisms are discussed basing on measurements of the unit cell volumes, Ce concentration uniformity, x-ray rocking spectra, absorption spectra of pure and variously doped LuAP crystals, and emission spectra under different excitations.

Electrophysiological characteristics of embryonic stem cell-derived cardiomyocytes are cell line-dependent.

PubMed

Hannes, Tobias; Wolff, Marie; Doss, Michael Xavier; Pfannkuche, Kurt; Haustein, Moritz; Müller-Ehmsen, Jochen; Sachinidis, Agapios; Hescheler, Jürgen; Khalil, Markus; Halbach, Marcel

2015-01-01

Modelling of cardiac development, physiology and pharmacology by differentiation of embryonic stem cells (ESCs) requires comparability of cardiac differentiation between different ESC lines. To investigate whether the outcome of cardiac differentiation is consistent between different ESC lines, we compared electrophysiological properties of ESC-derived cardiomyocytes (ESC-CMs) of different murine ESC lines. Two wild-type (D3 and R1) and two transgenic ESC lines (D3/aPIG44 and CGR8/AMPIGX-7) were differentiated under identical culture conditions. The transgenic cell lines expressed enhanced green fluorescent protein (eGFP) and puromycin-N-acetyltransferase under control of the cardiac specific α-myosin heavy chain (αMHC) promoter. Action potentials (APs) were recorded using sharp electrodes and multielectrode arrays in beating clusters of ESC-CMs. Spontaneous AP frequency and AP duration (APD) as well as maximal upstroke velocity differed markedly between unpurified CMs of the four ESC lines. APD heterogeneity was negligible in D3/aPIG44, moderate in D3 and R1 and extensive in CGR8/AMPIGX-7. Interspike intervals calculated from long-term recordings showed a high degree of variability within and between recordings in CGR8/AMPIGX-7, but not in D3/aPIG44. Purification of the αMHC+ population by puromycin treatment posed only minor changes to APD in D3/aPIG44, but significantly shortened APD in CGR8/AMPIGX-7. Electrophysiological properties of ESC-CMs are strongly cell line-dependent and can be influenced by purification of cardiomyocytes by antibiotic selection. Thus, conclusions on cardiac development, physiology and pharmacology derived from single stem cell lines have to be interpreted carefully. © 2015 S. Karger AG, Basel.

ParamAP: Standardized Parameterization of Sinoatrial Node Myocyte Action Potentials.

PubMed

Rickert, Christian; Proenza, Catherine

2017-08-22

Sinoatrial node myocytes act as cardiac pacemaker cells by generating spontaneous action potentials (APs). Much information is encoded in sinoatrial AP waveforms, but both the analysis and the comparison of AP parameters between studies is hindered by the lack of standardized parameter definitions and the absence of automated analysis tools. Here we introduce ParamAP, a standalone cross-platform computational tool that uses a template-free detection algorithm to automatically identify and parameterize APs from text input files. ParamAP employs a graphic user interface with automatic and user-customizable input modes, and it outputs data files in text and PDF formats. ParamAP returns a total of 16 AP waveform parameters including time intervals such as the AP duration, membrane potentials such as the maximum diastolic potential, and rates of change of the membrane potential such as the diastolic depolarization rate. ParamAP provides a robust AP detection algorithm in combination with a standardized AP parameter analysis over a wide range of AP waveforms and firing rates, owing in part to the use of an iterative algorithm for the determination of the threshold potential and the diastolic depolarization rate that is independent of the maximum upstroke velocity, a parameter that can vary significantly among sinoatrial APs. Because ParamAP is implemented in Python 3, it is also highly customizable and extensible. In conclusion, ParamAP is a powerful computational tool that facilitates quantitative analysis and enables comparison of sinoatrial APs by standardizing parameter definitions and providing an automated work flow. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The inhibitory effects of fluoroquinolones on L-carnitine transport in placental cell line BeWo.

PubMed

Hirano, Takeshi; Yasuda, Satoru; Osaka, Yuki; Asari, Masaru; Kobayashi, Masaki; Itagaki, Shirou; Iseki, Ken

2008-03-03

L-Carnitine plays an important role in lipid metabolism by facilitating the transport of long-chain fatty acids across the mitochondrial inner membrane followed by fatty acid beta-oxidation. It is known that members of the OCTN family play an important role in L-carnitine transport in the placenta. Investigation of drug-drug or drug-nutrient interaction in the placenta is important for establishment of safety drug medication during pregnancy. The aim of this study was to determine the effects of fluoroquinolones, inhibitors of OCTN2, on L-carnitine transport in the placenta which is known to have a high expression level of OCTN2. We investigated the inhibitory effect of five fluoroquinolones, ciprofloxacin (CPFX), gatifloxacin (GFLX), ofloxacin (OFLX), levofloxacin (LVFX) and grepafloxacin (GPFX), on L-carnitine transport mediated by OCTN2 in placental cell line BeWo cells. We found that all of the fluoroquinolones inhibited L-carnitine transport, GPFX being the strongest inhibitor. We also found that the inhibitory effects of LVFX and GPFX depended on their existence ratio of zwitterionic forms as, we reported previously. Furthermore, we elucidated the LVFX transport mechanism in BeWo cells. LVFX was transported actively by transporters. However, we found that LVFX transport was Na+-independent and l-carnitine had no inhibitory effect on LVFX transport, suggesting that LVFX acts as inhibitor of OCTN2, not as a substrate for OCTN2.

Preparing Students for the AP Psychology Exam

ERIC Educational Resources Information Center

Whitlock, Kristin

2013-01-01

The Advanced Placement Psychology exam is one of the fastest growing exams offered by the College Board. The average percent of change in the number of students taking this exam over the past five years is 12.4%. With 238,962 students taking the exam in 2013, the AP Psychology exam is the sixth largest exam, surpassing AP Biology and AP World…

Grounding line processes on the Totten Glacier

NASA Astrophysics Data System (ADS)

Cook, S.; Watson, C. S.; Galton-Fenzi, B.; Peters, L. E.; Coleman, R.

2017-12-01

The Totten Glacier has been an area of recent interest due to its large drainage basin, much of which is grounded below sea level and has a history of large scale grounding line movement. Reports that warm water reaches the sub-ice shelf cavity have led to speculation that it could be vulnerable to future grounding line retreat. Over the Antarctic summer 2016/17 an array of 6 GPS and autonomous phase-sensitive radar (ApRES) units were deployed in the grounding zone of the Totten Glacier. These instruments measure changes in ice velocity and thickness which can be used to investigate both ice dynamics across the grounding line, and the interaction between ice and ocean in the subglacial cavity. Basal melt rates calculated from the ApRES units on floating ice range from 1 to 17 m/a. These values are significantly lower than previous estimates of basal melt rate produced by ocean modelling of the subglacial cavity. Meanwhile, GPS-derived velocity and elevation on the surface of the ice show a strong tidal signal, as does the vertical strain rate within the ice derived from internal layering from the ApRES instruments. These results demonstrate the significance of the complex grounding pattern of the Totten Glacier. The presence of re-grounding points has significant implications for the dynamics of the glacier and the ocean circulation within the subglacial cavity. We discuss what can be learned from our in situ measurements, and how they can be used to improve models of the glacier's future behaviour.

Power Saving Control for Battery-Powered Portable WLAN APs

NASA Astrophysics Data System (ADS)

Ogawa, Masakatsu; Hiraguri, Takefumi

This paper proposes a power saving control function for battery-powered portable wireless LAN (WLAN) access points (APs) to extend the battery life. The IEEE802.11 standard does not support power saving control for APs. To enable a sleep state for an AP, the AP forces the stations (STAs) to refrain from transmitting frames using the network allocation vector (NAV) while the AP is sleeping. Thus the sleep state for the AP can be employed without causing frame loss at the STAs. Numerical analysis and computer simulation reveal that the newly proposed control technique conserves power compared to the conventional control.

Differences in the expression of endogenous efflux transporters in MDR1-transfected versus wildtype cell lines affect P-glycoprotein mediated drug transport

PubMed Central

Kuteykin-Teplyakov, Konstantin; Luna-Tortós, Carlos; Ambroziak, Kamila; Löscher, Wolfgang

2010-01-01

Background and purpose: P-glycoprotein (Pgp) efflux assays are widely used to identify Pgp substrates. The kidney cell lines Madin-Darby canine kidney (MDCK)-II and LLC-PK1, transfected with human MDR1 (ABCB1) are used to provide recombinant models of drug transport. Endogenous transporters in these cells may contribute to the activities of recombinant transporters, so that drug transport in MDR1-transfected cells is often corrected for the transport obtained in parental (wildtype) cells. However, expression of endogenous transporters may vary between transfected and wildtype cells, so that this correction may cause erroneous data. Here, we have measured the expression of endogenous efflux transporters in transfected and wildtype MDCK-II or LLC cells and the consequences for Pgp-mediated drug transport. Experimental approach: Using quantitative real-time RT-PCR, we determined the expression of endogenous Mdr1 mRNA and other efflux transporters in wildtype and MDR1-transfected MDCK-II and LLC cells. Transcellular transport was measured with the test substrate vinblastine. Key results: In MDR1-transfected MDCK cells, expression of endogenous (canine) Mdr1 and Mrp2 (Abcc2) mRNA was markedly lower than in wildtype cells, whereas MDR1-transfected LLC cells exhibited comparable Mdr1 but strikingly higher Mrp2 mRNA levels than wildtype cells. As a consequence, transport of vinblastine by human Pgp in efflux experiments was markedly underestimated when transport in MDR1-transfected MDCK cells was corrected for transport obtained in wildtype cells. This problem did not occur in LLC cells. Conclusions and implications: Differences in the expression of endogenous efflux transporters between transfected and wildtype MDCK cells provide a potential bias for in vitro studies on Pgp-mediated drug transport. PMID:20590635

Chromosome localization of human genes for clathrin adaptor polypeptides AP2{beta} and AP50 and the clathrin-binding protein, VCP

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

Druck, T.; Gu, Y.; Prabhala, G.

1995-11-01

Clathrin-coated vesicles, involved in endocytosis and Golgi processing, have a surface lattice containing clathrin triskelia and stoichiometric amounts of additional components termed {open_quotes}assembly proteins,{close_quotes} or APs. The AP form at the plasma membrane, AP2, is composed of two large subunits of 100-115 kDa, denoted AP2{alpha} and AP2{beta}, a medium chain of 50 kDa, designated AP50, and a small chain. We have determined human chromosomal locations of genes for a large AP2{beta} (CLAPB1) and a medium (CLAPM1) AP subunit and of a novel clathrin-binding protein, VCP, that binds clathrin simultaneously with A1`s. Chromosomal in situ hybridization of a human genomic clonemore » demonstrated that the CLAPM1 gene mapped to chromosome region 3q28. The gene for the CLAPB1 large subunit was mapped to 17q11.2-q12 by PCR amplification of an AP2{beta} fragment from a panel of rodent-human hybrid DNAs. To map the human VCP sequence, a human-specific probe was made by RT-PCR of human mRNA using oligonucleotide primers from conserved regions of the porcine sequence. The amplified human fragment served as probe on Southern blots of hybrid DNAs to determine that the human VCP locus maps to chromosome region 9pter-q34. 13 refs., 2 figs.« less

Diadenosine tetraphosphate (Ap4A) induces a diabetogenic situation: its impact on blood glucose, plasma insulin, gluconeogenesis, glucose uptake and GLUT-4 transporters.

PubMed

Verspohl, E J; Hohmeier, N; Lempka, M

2003-12-01

Diadenosine polyphosphates such as Ap4A are physiologically released compounds for which both receptors as well as a role as second messengers for influencing insulin release have been shown. So far little is known about their pathophysiological impact on diabetes with respect to blood glucose and plasma insulin, glucose production via gluconeogenesis, glucose uptake and GLUT-4 expression. Rats given an intravenous bolus of Ap4A (0.75 mg/kg) developed a rapid and dramatic increase in blood glucose. Plasma insulin was only transiently increased (for 4 min), but did not follow the normally stimulatory effect of the elevated blood glucose. A bolus of 25 microg Ap4A quickly increased glucose release from perfused rat liver. Glucose uptake was reduced in 3T3 adipocytes. Reduced amounts of translocated GLUT-4 were found in 3T3 cell membranes incubated with 10 microM Ap4A. Thus, Ap4A itself induces a diabetic situation which is likely to be mediated by an increase in gluconeogenesis and/or an insulin resistance caused by a decrease in GLUT-4 and an attenuation of glucose uptake.

AP Powerhouse Creates High Expectations for Dallas Students: Spreading the AP Challenge to Students and Teachers.

ERIC Educational Resources Information Center

Nelson, Colleen McCain

2001-01-01

Describes how veteran teacher Joan Vinson has made Advanced Placement (AP) a "cool thing to do" for minority students. With the help of private funding and a Texas-size enthusiasm, she is also convincing more teachers to take on the AP challenge, with a focus on quality over quantity. (EV)

AP-1 subunits: quarrel and harmony among siblings.

PubMed

Hess, Jochen; Angel, Peter; Schorpp-Kistner, Marina

2004-12-01

The AP-1 transcription factor is mainly composed of Jun, Fos and ATF protein dimers. It mediates gene regulation in response to a plethora of physiological and pathological stimuli, including cytokines, growth factors, stress signals, bacterial and viral infections, as well as oncogenic stimuli. Studies in genetically modified mice and cells have highlighted a crucial role for AP-1 in a variety of cellular events involved in normal development or neoplastic transformation causing cancer. However, emerging evidence indicates that the contribution of AP-1 to determination of cell fates critically depends on the relative abundance of AP-1 subunits, the composition of AP-1 dimers, the quality of stimulus, the cell type and the cellular environment. Therefore, AP-1-mediated regulation of processes such as proliferation, differentiation, apoptosis and transformation should be considered within the context of a complex dynamic network of signalling pathways and other nuclear factors that respond simultaneously.

Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration

PubMed Central

Dubos, Aline; Castells-Nobau, Anna; Meziane, Hamid; Oortveld, Merel A.W.; Houbaert, Xander; Iacono, Giovanni; Martin, Christelle; Mittelhaeuser, Christophe; Lalanne, Valérie; Kramer, Jamie M.; Bhukel, Anuradha; Quentin, Christine; Slabbert, Jan; Verstreken, Patrik; Sigrist, Stefan J.; Messaddeq, Nadia; Birling, Marie-Christine; Selloum, Mohammed; Stunnenberg, Henk G.; Humeau, Yann; Schenck, Annette; Herault, Yann

2015-01-01

ATP6AP2, an essential accessory component of the vacuolar H+ ATPase (V-ATPase), has been associated with intellectual disability (ID) and Parkinsonism. ATP6AP2 has been implicated in several signalling pathways; however, little is known regarding its role in the nervous system. To decipher its function in behaviour and cognition, we generated and characterized conditional knockdowns of ATP6AP2 in the nervous system of Drosophila and mouse models. In Drosophila, ATP6AP2 knockdown induced defective phototaxis and vacuolated photoreceptor neurons and pigment cells when depleted in eyes and altered short- and long-term memory when depleted in the mushroom body. In mouse, conditional Atp6ap2 deletion in glutamatergic neurons (Atp6ap2Camk2aCre/0 mice) caused increased spontaneous locomotor activity and altered fear memory. Both Drosophila ATP6AP2 knockdown and Atp6ap2Camk2aCre/0 mice presented with presynaptic transmission defects, and with an abnormal number and morphology of synapses. In addition, Atp6ap2Camk2aCre/0 mice showed autophagy defects that led to axonal and neuronal degeneration in the cortex and hippocampus. Surprisingly, axon myelination was affected in our mutant mice, and axonal transport alterations were observed in Drosophila. In accordance with the identified phenotypes across species, genome-wide transcriptome profiling of Atp6ap2Camk2aCre/0 mouse hippocampi revealed dysregulation of genes involved in myelination, action potential, membrane-bound vesicles and motor behaviour. In summary, ATP6AP2 disruption in mouse and fly leads to cognitive impairment and neurodegeneration, mimicking aspects of the neuropathology associated with ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system. PMID:26376863

Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration.

PubMed

Dubos, Aline; Castells-Nobau, Anna; Meziane, Hamid; Oortveld, Merel A W; Houbaert, Xander; Iacono, Giovanni; Martin, Christelle; Mittelhaeuser, Christophe; Lalanne, Valérie; Kramer, Jamie M; Bhukel, Anuradha; Quentin, Christine; Slabbert, Jan; Verstreken, Patrik; Sigrist, Stefan J; Messaddeq, Nadia; Birling, Marie-Christine; Selloum, Mohammed; Stunnenberg, Henk G; Humeau, Yann; Schenck, Annette; Herault, Yann

2015-12-01

ATP6AP2, an essential accessory component of the vacuolar H+ ATPase (V-ATPase), has been associated with intellectual disability (ID) and Parkinsonism. ATP6AP2 has been implicated in several signalling pathways; however, little is known regarding its role in the nervous system. To decipher its function in behaviour and cognition, we generated and characterized conditional knockdowns of ATP6AP2 in the nervous system of Drosophila and mouse models. In Drosophila, ATP6AP2 knockdown induced defective phototaxis and vacuolated photoreceptor neurons and pigment cells when depleted in eyes and altered short- and long-term memory when depleted in the mushroom body. In mouse, conditional Atp6ap2 deletion in glutamatergic neurons (Atp6ap2(Camk2aCre/0) mice) caused increased spontaneous locomotor activity and altered fear memory. Both Drosophila ATP6AP2 knockdown and Atp6ap2(Camk2aCre/0) mice presented with presynaptic transmission defects, and with an abnormal number and morphology of synapses. In addition, Atp6ap2(Camk2aCre/0) mice showed autophagy defects that led to axonal and neuronal degeneration in the cortex and hippocampus. Surprisingly, axon myelination was affected in our mutant mice, and axonal transport alterations were observed in Drosophila. In accordance with the identified phenotypes across species, genome-wide transcriptome profiling of Atp6ap2(Camk2aCre/0) mouse hippocampi revealed dysregulation of genes involved in myelination, action potential, membrane-bound vesicles and motor behaviour. In summary, ATP6AP2 disruption in mouse and fly leads to cognitive impairment and neurodegeneration, mimicking aspects of the neuropathology associated with ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system. © The Author 2015. Published by Oxford University Press.

Extracting potential bus lines of Customized City Bus Service based on public transport big data

NASA Astrophysics Data System (ADS)

Ren, Yibin; Chen, Ge; Han, Yong; Zheng, Huangcheng

2016-11-01

Customized City Bus Service (CCBS) can reduce the traffic congestion and environmental pollution that caused by the increasing in private cars, effectively. This study aims to extract the potential bus lines and each line's passenger density of CCBS by mining the public transport big data. The datasets used in this study are mainly Smart Card Data (SCD) and bus GPS data of Qingdao, China, from October 11th and November 7th 2015. Firstly, we compute the temporal-origin-destination (TOD) of passengers by mining SCD and bus GPS data. Compared with the traditional OD, TOD not only has the spatial location, but also contains the trip's boarding time. Secondly, based on the traditional DBSCAN algorithm, we put forwards an algorithm, named TOD-DBSCAN, combined with the spatial-temporal features of TOD.TOD-DBSCAN is used to cluster the TOD trajectories in peak hours of all working days. Then, we define two variables P and N to describe the possibility and passenger destiny of a potential CCBS line. P is the probability of the CCBS line. And N represents the potential passenger destiny of the line. Lastly, we visualize the potential CCBS lines extracted by our procedure on the map and analyse relationship between potential CCBS lines and the urban spatial structure.

PKC-dependent stimulation of the human MCT1 promoter involves transcription factor AP2.

PubMed

Saksena, Seema; Dwivedi, Alka; Gill, Ravinder K; Singla, Amika; Alrefai, Waddah A; Malakooti, Jaleh; Ramaswamy, Krishnamurthy; Dudeja, Pradeep K

2009-02-01

Monocarboxylate transporter (MCT1) plays an important role in the absorption of short-chain fatty acids (SCFA) such as butyrate in the human colon. Previous studies from our laboratory have demonstrated that phorbol ester, PMA (1 microM, 24 h), upregulates butyrate transport and MCT1 protein expression in human intestinal Caco-2 cells. However, the molecular mechanisms involved in the transcriptional regulation of MCT1 gene expression by PMA in the intestine are not known. In the present study, we showed that PMA (0.1 microM, 24 h) increased the MCT1 promoter activity (-871/+91) by approximately fourfold. A corresponding increase in MCT1 mRNA abundance in response to PMA was also observed. PMA-induced stimulation of MCT1 promoter activity was observed as early as 1 h and persisted until 24 h, suggesting that the effects of PMA are attributable to initial PKC activation. Kinase inhibitor and phosphorylation studies indicated that these effects may be mediated through activation of the atypical PKC-zeta isoform. 5'-deletion studies demonstrated that the MCT1 core promoter region (-229/+91) is the PMA-responsive region. Site-directed mutagenesis studies showed the predominant involvement of potential activator protein 2 (AP2) binding site in the activation of MCT1 promoter activity by PMA. In addition, overexpression of AP2 in Caco-2 cells significantly increased MCT1 promoter activity in a dose-dependent manner. These findings showing the regulation of MCT1 promoter by PKC and AP2 are of significant importance for an understanding of the molecular regulation of SCFA absorption in the human intestine.

Proactive AP Selection Method Considering the Radio Interference Environment

NASA Astrophysics Data System (ADS)

Taenaka, Yuzo; Kashihara, Shigeru; Tsukamoto, Kazuya; Yamaguchi, Suguru; Oie, Yuji

In the near future, wireless local area networks (WLANs) will overlap to provide continuous coverage over a wide area. In such ubiquitous WLANs, a mobile node (MN) moving freely between multiple access points (APs) requires not only permanent access to the Internet but also continuous communication quality during handover. In order to satisfy these requirements, an MN needs to (1) select an AP with better performance and (2) execute a handover seamlessly. To satisfy requirement (2), we proposed a seamless handover method in a previous study. Moreover, in order to achieve (1), the Received Signal Strength Indicator (RSSI) is usually employed to measure wireless link quality in a WLAN system. However, in a real environment, especially if APs are densely situated, it is difficult to always select an AP with better performance based on only the RSSI. This is because the RSSI alone cannot detect the degradation of communication quality due to radio interference. Moreover, it is important that AP selection is completed only on an MN, because we can assume that, in ubiquitous WLANs, various organizations or operators will manage APs. Hence, we cannot modify the APs for AP selection. To overcome these difficulties, in the present paper, we propose and implement a proactive AP selection method considering wireless link condition based on the number of frame retransmissions in addition to the RSSI. In the evaluation, we show that the proposed AP selection method can appropriately select an AP with good wireless link quality, i.e., high RSSI and low radio interference.

Peculiar Traits of Coarse AP

DTIC Science & Technology

2014-01-01

propellant. Since coarse AP in particles larger than about 150 microns are used in great majority for AP oxidized solid propellants, the nature of...Microscopic amounts of liquid containing water were contained in the reactive centers. The maximum size for reactive centers was reasoned to be...bond in the original chlorate ion. Oxygen atom swapping between chlorate and perchlorate ions would provide chlorate migration without use of forces

49 CFR 236.754 - Line, open wire.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Line, open wire. 236.754 Section 236.754 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Line, open wire. An overhead wire line consisting of single conductors as opposed to multiple-conductor...

49 CFR 236.754 - Line, open wire.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Line, open wire. 236.754 Section 236.754 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Line, open wire. An overhead wire line consisting of single conductors as opposed to multiple-conductor...

49 CFR 236.754 - Line, open wire.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Line, open wire. 236.754 Section 236.754 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Line, open wire. An overhead wire line consisting of single conductors as opposed to multiple-conductor...

49 CFR 236.754 - Line, open wire.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Line, open wire. 236.754 Section 236.754 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Line, open wire. An overhead wire line consisting of single conductors as opposed to multiple-conductor...

49 CFR 236.754 - Line, open wire.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Line, open wire. 236.754 Section 236.754 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Line, open wire. An overhead wire line consisting of single conductors as opposed to multiple-conductor...

Paracellular transport through healthy and cystic fibrosis bronchial epithelial cell lines--do we have a proper model?

PubMed

Molenda, Natalia; Urbanova, Katarina; Weiser, Nelly; Kusche-Vihrog, Kristina; Günzel, Dorothee; Schillers, Hermann

2014-01-01

It has been reported recently that the cystic fibrosis transmembrane conductance regulator (CFTR) besides transcellular chloride transport, also controls the paracellular permeability of bronchial epithelium. The aim of this study was to test whether overexpressing wtCFTR solely regulates paracellular permeability of cell monolayers. To answer this question we used a CFBE41o- cell line transfected with wtCFTR or mutant F508del-CFTR and compered them with parental line and healthy 16HBE14o- cells. Transepithelial electrical resistance (TER) and paracellular fluorescein flux were measured under control and CFTR-stimulating conditions. CFTR stimulation significant decreased TER in 16HBE14o- and also in CFBE41o- cells transfected with wtCFTR. In contrast, TER increased upon stimulation in CFBE41o- cells and CFBE41o- cells transfected with F508del-CFTR. Under non-stimulated conditions, all four cell lines had similar paracellular fluorescein flux. Stimulation increased only the paracellular permeability of the 16HBE14o- cell monolayers. We observed that 16HBE14o- cells were significantly smaller and showed a different structure of cell-cell contacts than CFBE41o- and its overexpressing clones. Consequently, 16HBE14o- cells have about 80% more cell-cell contacts through which electrical current and solutes can leak. Also tight junction protein composition is different in 'healthy' 16HBE14o- cells compared to 'cystic fibrosis' CFBE41o- cells. We found that claudin-3 expression was considerably stronger in 16HBE14o- cells than in the three CFBE41o- cell clones and thus independent of the presence of functional CFTR. Together, CFBE41o- cell line transfection with wtCFTR modifies transcellular conductance, but not the paracellular permeability. We conclude that CFTR overexpression is not sufficient to fully reconstitute transport in CF bronchial epithelium. Hence, it is not recommended to use those cell lines to study CFTR-dependent epithelial transport.

49 CFR 192.377 - Service lines: Copper.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Service lines: Copper. 192.377 Section 192.377 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.377 Service lines: Copper. Each copper service line installed within a building must be protected...

49 CFR 192.377 - Service lines: Copper.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Service lines: Copper. 192.377 Section 192.377 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.377 Service lines: Copper. Each copper service line installed within a building must be protected...

VizieR Online Data Catalog: Water masers in M31. I. Recombination lines (Darling+, 2016)

NASA Astrophysics Data System (ADS)

Darling, J.; Gerard, B.; Amiri, N.; Lawrence, K.

2016-09-01

We constructed a catalog of 506 unresolved 24um sources from the Spitzer 24um map of M31 (Gordon et al. 2006ApJ...638L..87G); see Figure 1. Darling (2011ApJ...732L...2D) observed 206 24um sources in M31 using the Green Bank Telescope (GBT) in 2010 October through December. The 616-523 22.23508GHz ortho-water maser line observations were reported in Darling (2011ApJ...732L...2D), but simultaneous observations of the para-ammonia (NH3) rotational ground-state inversion transitions in the metastable states (J,K)=(1,1) and (2,2) at 23.6945 and 23.72263GHz, respectively, and the hydrogen recombination line H66α at 22.36417GHz were not. We subsequently observed all four of these lines toward an additional 300 24um sources in 2011 October through 2012 January. The resolution of the 24um Spitzer image is 6" (Gordon et al. 2006ApJ...638L..87G), so the unresolved IR sources remained within the 33" GBT beam even during the largest pointing drifts. The 33" beam (FWHM) at 22GHz spans 125pc in M31. (1 data file).

AP Human Geography and Success on the AP Test

ERIC Educational Resources Information Center

Roncone, John; Newhalfen, Nate

2013-01-01

Classroom projects that explore culture and globalization enhance the curriculum and help students see how geography directly connects to their lives. These authors contend that a project-based approach can supplement the teaching of an AP Human Geography course, and visualize this course as an essential tool for students to truly understand how…

6-Mercaptopurine transport by equilibrative nucleoside transporters in conditionally immortalized rat syncytiotrophoblast cell lines TR-TBTs.

PubMed

Lee, Na-young; Sai, Yoshimichi; Nakashima, Emi; Ohtsuki, Sumio; Kang, Young-sook

2011-09-01

Recently, more women were provided with 6-mercaptopurine (6-MP) during pregnancy. Therefore, we attempted to clarify the transport mechanisms of 6-MP through blood-placenta barrier using rat conditionally immortalized syncytiotrophoblast cell lines (TR-TBTs). The uptake of 6-MP was time- and ATP dependent, but sodium independent in TR-TBTs. 6-MP was eliminated over 50% from the cells within 30 min. The uptake of 6-MP was saturable with Michaelis-Menten constant values of 198 μM and 250 μM in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. 6-Thioguanine, azathioprine, and hypoxantine, structural analogues of 6-MP, strongly inhibited [(14) C]6-MP uptake. Equilibrative nucleoside transporter (ENT) inhibitors, adenosine and uridine, significantly inhibited [(14) C]6-MP uptake. However, several organic anions and cations had no effect on [(14) C]6-MP uptake in TR-TBTs. These results suggest that sodium-independent transporters, ENTs, may be involved in 6-MP uptake at the placenta. In addition, multidrug resistance protein (MRP) inhibitors, methotrexate, probenecid, cefmetazole, and sulfinpyrazone, significantly increased the accumulation of [(14) C]6-MP in the cells. It is indicated that 6-MP may be eliminated across the blood-placental barrier via MRPs. TR-TBTs expressed mRNA of ENT1, ENT2, MRP4, and MRP5. These findings are important for the therapy of acute lymphoblastic leukemia and autoimmune diseases of pregnant women, and should be useful data in elucidating teratogenicity of 6-MP during pregnancy. Copyright © 2011 Wiley-Liss, Inc.

49 CFR 192.371 - Service lines: Steel.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Service lines: Steel. 192.371 Section 192.371 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.371 Service lines: Steel. Each steel service line to be operated at less than 100 p.s.i. (689 kPa...

49 CFR 192.371 - Service lines: Steel.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Service lines: Steel. 192.371 Section 192.371 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.371 Service lines: Steel. Each steel service line to be operated at less than 100 p.s.i. (689 kPa...

49 CFR 192.371 - Service lines: Steel.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Service lines: Steel. 192.371 Section 192.371 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.371 Service lines: Steel. Each steel service line to be operated at less than 100 p.s.i. (689 kPa...

49 CFR 192.371 - Service lines: Steel.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Service lines: Steel. 192.371 Section 192.371 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.371 Service lines: Steel. Each steel service line to be operated at less than 100 p.s.i. (689 kPa...

49 CFR 192.371 - Service lines: Steel.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Service lines: Steel. 192.371 Section 192.371 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.371 Service lines: Steel. Each steel service line to be operated at less than 100 p.s.i. (689 kPa...

QSO Narrow [OIII] Line Width and Host Galaxy Luminosity

NASA Astrophysics Data System (ADS)

Bonning, E. W.; Shields, G. A.; Salviander, S.

2004-05-01

Established correlations between galaxy bulge luminosity L, black hole mass MBH, and stellar velocity dispersion sigma in galaxies suggest a close relationship between the growth of supermassive black holes and their host galaxies. Measurements of the MBH - sigma relationship as a function of cosmic time may shed light on the origin of this relationship. One approach is to derive MBH and sigma from the widths of QSO broad and narrow lines, respectively (Shields et al. 2003, ApJ, 583, 124; Nelson 2000, ApJ, 544, L91). We investigate the utility of using the velocity of the narrow line emitting gas as a surrogate for stellar velocity dispersion in QSOs by examining host magnitudes and [OIII] line widths for low redshift QSOs. For our limited range of L, the increase in sigma with L predicted by the Faber-Jackson relation is substantially obscured by scatter. However, sigma([O III]) is consistent in the mean with host galaxy luminosity. EWB is a NASA GSRP fellow. GAS and SS are supported under Texas Advanced Research Program grant 003658-0177-2001 and NSF grant AST-0098594.

Unexpected Heterodivalent Recruitment of NOS1AP to nNOS Reveals Multiple Sites for Pharmacological Intervention in Neuronal Disease Models.

PubMed

Li, Li-Li; Melero-Fernandez de Mera, Raquel M; Chen, Jia; Ba, Wei; Kasri, Nael Nadif; Zhang, Mingjie; Courtney, Michael J

2015-05-13

The protein NOS1AP/CAPON mediates signaling from a protein complex of NMDA receptor, PSD95 and nNOS. The only stroke trial for neuroprotectants that showed benefit to patients targeted this ternary complex. NOS1AP/nNOS interaction regulates small GTPases, iron transport, p38MAPK-linked excitotoxicity, and anxiety. Moreover, the nos1ap gene is linked to disorders from schizophrenia, post-traumatic stress disorder, and autism to cardiovascular disorders and breast cancer. Understanding protein interactions required for NOS1AP function, therefore, has broad implications for numerous diseases. Here we show that the interaction of NOS1AP with nNOS differs radically from the classical PDZ docking assumed to be responsible. The NOS1AP PDZ motif does not bind nNOS as measured by multiple methods. In contrast, full-length NOS1AP forms an unusually stable interaction with nNOS. We mapped the discrepancy between full-length and C-terminal PDZ motif to a novel internal region we call the ExF motif. The C-terminal PDZ motif, although neither sufficient nor necessary for binding, nevertheless promotes the stability of the complex. It therefore potentially affects signal transduction and suggests that functional interaction of nNOS with NOS1AP might be targetable at two distinct sites. We demonstrate that excitotoxic pathways can be regulated, in cortical neuron and organotypic hippocampal slice cultures from rat, either by the previously described PDZ ligand TAT-GESV or by the ExF motif-bearing region of NOS1AP, even when lacking the critical PDZ residues as long as the ExF motif is intact and not mutated. This previously unrecognized heterodivalent interaction of nNOS with NOS1AP may therefore provide distinct opportunities for pharmacological intervention in NOS1AP-dependent signaling and excitotoxicity. Copyright © 2015 the authors 0270-6474/15/357349-16$15.00/0.

Constitutive mRNA expression and protein activity levels of nine ABC efflux transporters in seven permanent cell lines derived from different tissues of rainbow trout (Oncorhynchus mykiss).

PubMed

Fischer, Stephan; Loncar, Jovica; Zaja, Roko; Schnell, Sabine; Schirmer, Kristin; Smital, Tvrtko; Luckenbach, Till

2011-01-25

Permanent fish cell lines have become common model systems for determining ecotoxicological effects of pollutants. For these cell lines little is known on the cellular active transport mechanisms that control the amount of a compound entering the cell, such as the MXR (multixenobiotic resistance) system mediated by ATP binding cassette (ABC) transport proteins. Therefore, for toxic evaluation of chemicals with those cells information on MXR is important. We here present data on constitutive mRNA expression and protein activity levels of a series of ABC efflux transporters in seven permanent cell lines derived from liver (RTL-W1; R1) and liver hepatoma (RTH-149), gill (RTgill-W1), gonad (RTG-2), gut (RTgutGC) and brain (RTbrain) of rainbow trout (Oncorhynchus mykiss). In addition to known transporters abcb1 (designated here abcb1a), abcb11, abcc1-3, abcc5 and abcg2, we quantified expression levels of a newly identified abcb1 isoform (abcb1b) and abcc4, previously unknown in trout. Quantitative real time PCR (qPCR) indicated that mRNA of the examined ABC transporters was constitutively expressed in all cell lines. Transporter mRNA expression patterns were similar in all cell lines, with expression levels of abcc transporters being 80 to over 1000 fold higher than for abcg2, abcb1a/b and abcb11 (abcc1-5>abcg2>abcb1a/b, 11). Transporter activity in the cell lines was determined by measuring uptake of transporter type specific fluorescent substrates in the presence of activity inhibitors. The combination of the ABCB1 and ABCC transporter substrate calcein-AM with inhibitors cyclosporine A, PSC833 and MK571 resulted in a concentration-dependent fluorescence increase of up to 3-fold, whereas reversin 205 caused a slight, but not concentration-dependent fluorescence increase. Accumulation of the dyes Hoechst 33342 and 2',7'-dichlorodihydrofluorescein diacetate was basically unchanged in the presence of Ko134 and taurocholate, respectively, indicating low Abcg2 and Abcb11

AP Courses Get Audited for Quality

ERIC Educational Resources Information Center

Ashford, Ellie

2007-01-01

As the college admissions process has gotten much more competitive, the number of high school students taking Advanced Placement (AP) courses has soared. At the same time, policymakers and education leaders seek to get more minorities and students not on the college track to sign up for AP and other rigorous classes. But as high schools have…

Michigan transportation facts & figures : public transportation

DOT National Transportation Integrated Search

2002-08-16

This on-line document is part of a series, Transportation Facts & Figures, by the Michigan Department of Transportation (MDOT). The Public Transit section of Transportation Facts & Figures cover such topics as intercity bus service, intercity rail se...

Analogs of diadenosine tetraphosphate (Ap4A).

PubMed

Guranowski, Andrzej

2003-01-01

This review summarizes our knowledge of analogs and derivatives of diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A), the most extensively studied member of the dinucleoside 5',5"'-P1,Pn-polyphosphate (NpnN) family. After a short discussion of enzymes that may be responsible for the accumulation and degradation of Np4)N's in the cell, this review focuses on chemically and/or enzymatically produced analogs and their practical applications. Particular attention is paid to compounds that have aided the study of enzymes involved in the metabolism of Ap4A (Np4N'). Certain Ap4A analogs were alternative substrates of Ap4A-degrading enzymes and/or acted as enzyme inhibitors, some other helped to establish enzyme mechanisms, increased the sensitivity of certain enzyme assays or produced stable enzyme:ligand complexes for structural analysis.

A summary of recent developments in transportation hazard classification activities for ammonium perchlorate

NASA Technical Reports Server (NTRS)

Koller, A. M., Jr.; Hannum, J. A. E.

1983-01-01

The transportation hazard classification of Ammonium Perchlorate is discussed. A test program was completed and data were forwarded to retain a Class 5.1 designation (oxidizer) for AP which is shipped internationally. As a follow-on to the initial team effort to conduct AP tests existing data were examined and a matrix which catalogs test parameters and findings was compiled. A collection of test protocols is developed to standardize test methods for energetic materials of all types. The actions to date are summarized; the participating organizations and their roles as presently understood; specific findings on AP (matrix); and issues, lessons learned, and potential actions of particular interest to the propulsion community which may evolve as a result of future U.N. propellant transportation classification activities.

Ion transport in a human lens epithelial cell line exposed to hyposmotic and apoptotic stress.

PubMed

Chimote, Ameet A; Adragna, Norma C; Lauf, Peter K

2010-04-01

Membrane transport changes in human lens epithelial (HLE-B3) cells under hyposmotic and apoptotic stress were compared. Cell potassium content, K(i), uptake of the K congener rubidium, Rb(i), and water content were measured after hyposmotic stress induced by hypotonicity, and apoptotic stress by the protein-kinase inhibitor staurosporine (STP). Cell water increased in hyposmotic (150 mOsm) as compared to isosmotic (300 mOsm) balanced salt solution (BSS) by >2-fold at 5 min and decreased within 15 min to baseline values accompanied by a 40% K(i) loss commensurate with cell swelling and subsequent cell shrinkage likely due to regulatory volume decrease (RVD). Loss of K(i), and accompanying water, and Rb(i) uptake in hyposmotic BSS were prevented by clotrimazole (CTZ) suggesting water shifts associated with K and Rb flux via intermediate conductance K (IK) channels, also detected at the mRNA and protein level. In contrast, 2 h after 2 microM STP exposure, the cells lost approximately 40% water and approximately 60% K(i), respectively, consistent with apoptotic volume decrease (AVD). Indeed, water and K(i) loss was at least fivefold greater after hyposmotic than after apoptotic stress. High extracellular K and 2 mM 4-aminopyridine (4-AP) but not CTZ significantly reduced apoptosis. Annexin labeling phosphatidylserine (PS) at 15 min suggested loss of lipid asymmetry. Quantitative PCR revealed significant IK channel expression during prolonged hyposmotic stress. Results suggest in HLE-B3 cells, IK channels likely partook in and were down regulated after RVD, whereas pro-apoptotic STP-activation of 4-AP-sensitive voltage-gated K channels preceded or accompanied PS externalization before subsequent apoptosis. J. Cell. Physiol. 223: 110-122, 2010. (c) 2009 Wiley-Liss, Inc.

Design of the low energy beam transport line for the China spallation neutron source

NASA Astrophysics Data System (ADS)

Li, Jin-Hai; Ouyang, Hua-Fu; Fu, Shi-Nian; Zhang, Hua-Shun; He, Wei

2008-03-01

The design of the China Spallation Neutron Source (CSNS) low-energy beam transport (LEBT) line, which locates between the ion source and the radio-frequency quadrupole (RFQ), has been completed with the TRACE3D code. The design aims at perfect matching, primary chopping, a small emittance growth and sufficient space for beam diagnostics. The line consists of three solenoids, three vacuum chambers, two steering magnets and a pre-chopper. The total length of LEBT is about 1.74 m. This LEBT is designed to transfer 20 mA of H-pulsed beam from the ion source to the RFQ. An induction cavity is adopted as the pre-chopper. The electrostatic octupole steerer is discussed as a candidate. A four-quadrant aperture for beam scraping and beam position monitoring is designed.

ONLINE MINIMIZATION OF VERTICAL BEAM SIZES AT APS

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

Sun, Yipeng

In this paper, online minimization of vertical beam sizes along the APS (Advanced Photon Source) storage ring is presented. A genetic algorithm (GA) was developed and employed for the online optimization in the APS storage ring. A total of 59 families of skew quadrupole magnets were employed as knobs to adjust the coupling and the vertical dispersion in the APS storage ring. Starting from initially zero current skew quadrupoles, small vertical beam sizes along the APS storage ring were achieved in a short optimization time of one hour. The optimization results from this method are briefly compared with the onemore » from LOCO (Linear Optics from Closed Orbits) response matrix correction.« less

apGA: An adaptive parallel genetic algorithm

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

Liepins, G.E.; Baluja, S.

1991-01-01

We develop apGA, a parallel variant of the standard generational GA, that combines aggressive search with perpetual novelty, yet is able to preserve enough genetic structure to optimally solve variably scaled, non-uniform block deceptive and hierarchical deceptive problems. apGA combines elitism, adaptive mutation, adaptive exponential scaling, and temporal memory. We present empirical results for six classes of problems, including the DeJong test suite. Although we have not investigated hybrids, we note that apGA could be incorporated into other recent GA variants such as GENITOR, CHC, and the recombination stage of mGA. 12 refs., 2 figs., 2 tabs.

A Fe K Line in GRB 970508

NASA Astrophysics Data System (ADS)

Protassov, R.; van Dyk, D.; Connors, A.; Kashyap, V.; Siemiginowska, A.

2000-12-01

We examine the x-ray spectrum of the afterglow of GRB 970508, analyzed for Fe line emission by Piro et al (1999, ApJL, 514, L73). This is a difficult and extremely important measurement: the detection of x-ray afterglows from γ -ray bursts is at best a tricky business, relying on near-real satellite time response to unpredictable events; and a great deal of luck in catching a burst bright enough for a useful spectral analysis. Detecting a clear atomic (or cyclotron) line in the generally smooth and featureless afterglow (or burst) emission not only gives one of the few very specific keys to the physics local to the emission region, but also provides clues or confirmation of its distance (via redshift). Unfortunately, neither the likelihood ratio test or the related F-statistic commonly used to detect spectral lines adhere to their nominal Chi square and F-distributions. Thus we begin by calibrating the F-statistic used in Piro et al (1999, ApJL, 514, L73) via a simulation study. The simulation study relies on a completely specified source model, i.e. we do Monte Carlo simulations with all model parameters fixed (so--called ``parametric bootstrapping''). Second, we employ the method of posterior predictive p-values to calibrate a LRT statistic while accounting for the uncertainty in the parameters of the source model. Our analysis reveals evidence for the Fe K line.

Optimization of solenoid based low energy beam transport line for high current H+ beams

NASA Astrophysics Data System (ADS)

Pande, R.; Singh, P.; Rao, S. V. L. S.; Roy, S.; Krishnagopal, S.

2015-02-01

A 20 MeV, 30 mA CW proton linac is being developed at BARC, Mumbai. This linac will consist of an ECR ion source followed by a Radio Frequency Quadrupole (RFQ) and Drift tube Linac (DTL). The low energy beam transport (LEBT) line is used to match the beam from the ion source to the RFQ with minimum beam loss and increase in emittance. The LEBT is also used to eliminate the unwanted ions like H2+ and H3+ from entering the RFQ. In addition, space charge compensation is required for transportation of such high beam currents. All this requires careful design and optimization. Detailed beam dynamics simulations have been done to optimize the design of the LEBT using the Particle-in-cell code TRACEWIN. We find that with careful optimization it is possible to transport a 30 mA CW proton beam through the LEBT with 100% transmission and minimal emittance blow up, while at the same time suppressing unwanted species H2+ and H3+ to less than 3.3% of the total beam current.

Radiation protection considerations along a radioactive ion beam transport line

NASA Astrophysics Data System (ADS)

Sarchiapone, Lucia; Zafiropoulos, Demetre

2016-09-01

The goal of the SPES project is to produce accelerated radioactive ion beams for Physics studies at “Laboratori Nazionali di Legnaro” (INFN, Italy). This accelerator complex is scheduled to be built by 2016 for an effective operation in 2017. Radioactive species are produced in a uranium carbide target, by the interaction of 200 μA of protons at 40 MeV. All of the ionized species in the 1+ state come out of the target (ISOL method), and pass through a Wien filter for a first selection and an HMRS (high mass resolution spectrometer). Then they are transported by an electrostatic beam line toward a charge state breeder (where the 1+ to n+ multi-ionization takes place) before selection and reacceleration at the already existing superconducting linac. The work concerning dose evaluations, activation calculation, and radiation protection constraints related to the transport of the radioactive ion beam (RIB) from the target to the mass separator will be described in this paper. The FLUKA code has been used as tool for those calculations needing Monte Carlo simulations, in particular for the evaluation of the dose rate due to the presence of the radioactive beam in the selection/interaction points. The time evolution of a radionuclide inventory can be computed online with FLUKA for arbitrary irradiation profiles and decay times. The activity evolution is analytically evaluated through the implementation of the Bateman equations. Furthermore, the generation and transport of decay radiation (limited to gamma, beta- and beta+ emissions) is possible, referring to a dedicated database of decay emissions using mostly information obtained from NNDC, sometimes supplemented with other data and checked for consistency. When the use of Monte Carlo simulations was not feasible, the Bateman equations, or possible simplifications, have been used directly.

Statistical properties of links of network: A survey on the shipping lines of Worldwide Marine Transport Network

NASA Astrophysics Data System (ADS)

Zhang, Wenjun; Deng, Weibing; Li, Wei

2018-07-01

Node properties and node importance identification of networks have been vastly studied in the last decades. While in this work, we analyze the links' properties of networks by taking the Worldwide Marine Transport Network (WMTN) as an example, i.e., statistical properties of the shipping lines of WMTN have been investigated in various aspects: Firstly, we study the feature of loops in the shipping lines by defining the line saturability. It is found that the line saturability decays exponentially with the increase of line length. Secondly, to detect the geographical community structure of shipping lines, the Label Propagation Algorithm with compression of Flow (LPAF) and Multi-Dimensional Scaling (MDS) method are employed, which show rather consistent communities. Lastly, to analyze the redundancy property of shipping lines of different marine companies, the multilayer networks are constructed by aggregating the shipping lines of different marine companies. It is observed that the topological quantities, such as average degree, average clustering coefficient, etc., increase smoothly when marine companies are randomly merged (randomly choose two marine companies, then merge the shipping lines of them together), while the relative entropy decreases when the merging sequence is determined by the Jensen-Shannon distance (choose two marine companies when the Jensen-Shannon distance between them is the lowest). This indicates the low redundancy of shipping lines among different marine companies.

Turbulent transport of He II in active and passive phase separators using slit devices and porous media

NASA Technical Reports Server (NTRS)

Yuan, S. W. K.; Lee, J. M.; Frederking, T. H. K.

1988-01-01

The turbulent transport mode of vapor liquid phase separators (VLPS) for He II has been investigated comparing passive porous plug separators with active phase separators (APS) using slits of variable flow paths within a common frame of reference. It is concluded that the basic transport regimes in both devices are identical. An integrated Gorter-Mellink (1949) equation, found previously to predict VLPS results of porous plugs, is employed to analyze APS data published in the literature. It is found that the Gorter-Mellink flow rate parameter for 9-micron and 14-micron APS slit widths are relatively independent of the slit width, having a rate constant of about 9 + or - 10 percent. This agrees with the early heat flow results for He II entropy transport at zero net mass flow in wide capillaries and slits.

APS deposition facility upgrades and future plans

NASA Astrophysics Data System (ADS)

Conley, Ray; Shi, Bing; Erdmann, Mark; Izzo, Scott; Assoufid, Lahsen; Goetze, Kurt; Mooney, Tim; Lauer, Kenneth

2014-09-01

The Advanced Photon Source (APS) has recently invested resources to upgrade or replace aging deposition systems with modern equipment. Of the three existing deposition systems, one will receive an upgrade, while two are being replaced. A design which adds a three-substrate planetary for the APS rotary deposition system is almost complete. The replacement for the APS large deposition system, dubbed the "Modular Deposition System", has been conceptually designed and is in the procurement process. Eight cathodes will sputter horizontally on mirrors up to 1.5 meters in length. This new instrument is designed to interface with ion-milling instruments and various metrology equipment for ion-beam figuring. A third linear machine, called the APS Profile Coating System, has two cathodes and is designed to accept substrates up to 200mm in length. While this machine is primarily intended for fabrication of figured KB mirrors using the profile-coating technique, it has also been used to produce multilayer monochromators for beamline use.

75 FR 75666 - Advanced Placement (AP) Test Fee Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-06

... DEPARTMENT OF EDUCATION [CFDA No. 84.330B] Advanced Placement (AP) Test Fee Program AGENCY: Office... AP Test Fee fiscal year (FY) 2011 competition. SUMMARY: On September 1, 2010, we published in the Federal Register (75 FR 53681) a notice inviting applications for the AP Test Fee FY 2011 competition...

Significance of the Lateral Humeral Line for Evaluating Radiocapitellar Alignment in Children.

PubMed

Souder, Christopher D; Roocroft, Joanna H; Edmonds, Eric W

The radiocapitellar line (RCL) was originally described for evaluation of the alignment of the RC joint on lateral images of the elbow. Although, many authors have translated the utilization of RCL into coronal imaging, previous studies have not been performed to confirm validity. The purpose of this paper was to identify an accurate way of evaluating pediatric RC alignment in the coronal plane. Thirty-seven anteroposterior (AP) radiographs of 37 children were evaluated to determine the position of the RC joint in the coronal plane. All had acceptable magnetic resonance imaging (MRI) studies available for comparison. The lateral humeral line (LHL), consisting of a line along the lateral edge of the ossified condyle of the distal humerus parallel to the axis of the distal humeral shaft, was studied as it related to the lateral cortex of the radial neck. Three children with a confirmed diagnosis of a Bado III, lateral displaced radius, Monteggia fracture were also evaluated. The LHL passed along the edge of or lateral to the radial neck on all AP radiographs and all MRI studies. The RCL failed to intersect the capitellum on 2 AP radiographs. On MRI, the RCL also passed lateral to the capitellar ossification center in 3 patients. In addition, the RCL was seen passing through the capitellum at a mean of the lateral 30% (range, 0% to 64%) on AP radiographs and 26% (range, 0% to 48%) on MRI. For all 3 children with a Bado III Monteggia fracture, the LHL crossed the radial neck and the RCL did not intersect the capitellum. The RCL can fail to intersect the capitellar ossification center on AP radiographs and MRI in pediatric elbows without injury. The LHL consistently lies lateral to the radial neck in normal elbows and medial to the lateral aspect of the radial neck on all Bado III fracture-dislocations. It, therefore, can be used as an adjunct in evaluating the RC joint on AP imaging. The RCL most commonly intersects the lateral one third of the ossification center on

X Linkage of AP3A, a Homolog of the Y-Linked MADS-Box Gene AP3Y in Silene latifolia and S. dioica

PubMed Central

Penny, Rebecca H.; Montgomery, Benjamin R.; Delph, Lynda F.

2011-01-01

Background The duplication of autosomal genes onto the Y chromosome may be an important element in the evolution of sexual dimorphism.A previous cytological study reported on a putative example of such a duplication event in a dioecious tribe of Silene (Caryophyllaceae): it was inferred that the Y-linked MADS-box gene AP3Y originated from a duplication of the reportedly autosomal orthologAP3A. However, a recent study, also using cytological methods, indicated that AP3A is X-linked in Silenelatifolia. Methodology/Principal Findings In this study, we hybridized S. latifolia and S. dioicato investigate whether the pattern of X linkage is consistent among distinct populations, occurs in both species, and is robust to genetic methods. We found inheritance patterns indicative of X linkage of AP3A in widely distributed populations of both species. Conclusions/Significance X linkage ofAP3A and Y linkage of AP3Yin both species indicates that the genes' ancestral progenitor resided on the autosomes that gave rise to the sex chromosomesand that neither gene has moved between chromosomes since species divergence.Consequently, our results do not support the contention that inter-chromosomal gene transfer occurred in the evolution of SlAP3Y from SlAP3A. PMID:21533056

Incorporating the APS Catalog of the POSS I and Image Archive in ADS

NASA Technical Reports Server (NTRS)

Humphreys, Roberta M.

1998-01-01

The primary purpose of this contract was to develop the software to both create and access an on-line database of images from digital scans of the Palomar Sky Survey. This required modifying our DBMS (called Star Base) to create an image database from the actual raw pixel data from the scans. The digitized images are processed into a set of coordinate-reference index and pixel files that are stored in run-length files, thus achieving an efficient lossless compression. For efficiency and ease of referencing, each digitized POSS I plate is then divided into 900 subplates. Our custom DBMS maps each query into the corresponding POSS plate(s) and subplate(s). All images from the appropriate subplates are retrieved from disk with byte-offsets taken from the index files. These are assembled on-the-fly into a GIF image file for browser display, and a FITS format image file for retrieval. The FITS images have a pixel size of 0.33 arcseconds. The FITS header contains astrometric and photometric information. This method keeps the disk requirements manageable while allowing for future improvements. When complete, the APS Image Database will contain over 130 Gb of data. A set of web pages query forms are available on-line, as well as an on-line tutorial and documentation. The database is distributed to the Internet by a high-speed SGI server and a high-bandwidth disk system. URL is http://aps.umn.edu/IDB/. The image database software is written in perl and C and has been compiled on SGI computers with MIX5.3. A copy of the written documentation is included and the software is on the accompanying exabyte tape.

Dissociation between the effects of P1, P4-diadenosine tetraphosphate (Ap4A) on renal haemodynamics and tubular function in anaesthetized rats.

PubMed

Jankowski, M; Angielski, S; Szczepańska-Konkel, M

2008-03-01

Previous studies from our laboratory have reported a marked reduction in glomerular filtration rate (GFR) and sodium reabsorption in renal proximal tubule during intravenous infusion of P(1),P(4)-diadenosine tetraphosphate (Ap(4)A) at dose of 1.0 micromol/kg + 10 nmol/kg/min (i.v., injection followed by infusion) in anaesthetized Wistar rats. In the present study, the changes of GFR and urine sodium excretion were investigated in response to systemic infusion of Ap(4)A at different doses. Ap(4)A at dose of 0.1 micromol/kg + 1.0 nmol/kg/min did not change GFR and sodium urinary excretion whereas 2-fold higher dose produced significant (3.4-fold) increase in sodium excretion without changes in GFR. Significant but transient reduction in GFR by approximately 21% was observed during infusion of Ap(4)A at dose of 0.5 micromol/kg + 5.0 nmol/kg/min. Higher doses of Ap(4)A (1.0 micromol/kg + 10 nmol/kg/min and 2.0 micromol/kg + 20 nmol/kg/min) reduction in GFR and marked natriuresis. Our results suggest that tubular sodium transport systems are more sensitive to Ap(4)A than systems involved in GFR regulation.

Expression of Death Receptor 4 Is Positively Regulated by MEK/ERK/AP-1 Signaling and Suppressed upon MEK Inhibition*

PubMed Central

Yao, Weilong; Oh, You-Take; Deng, Jiusheng; Yue, Ping; Deng, Liang; Huang, Henry; Zhou, Wei; Sun, Shi-Yong

2016-01-01

Death receptor 4 (DR4) is a cell surface receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and triggers apoptosis upon ligation with TRAIL or aggregation. MEK/ERK signaling is a well known and the best-studied effector pathway downstream of Ras and Raf. This study focuses on determining the impact of pharmacological MEK inhibition on DR4 expression and elucidating the underlying mechanism. We found that several MEK inhibitors including MEK162, AZD6244, and PD0325901 effectively decreased DR4 protein levels including cell surface DR4 in different cancer cell lines. Accordingly, pre-treatment of TRAIL-sensitive cancer cell lines with a MEK inhibitor desensitized them to TRAIL-induced apoptosis. These results indicate that MEK inhibition negatively regulates DR4 expression and cell response to TRAIL-induced apoptosis. MEK inhibitors did not alter DR4 protein stability, rather decreased its mRNA levels, suggesting a transcriptional regulation. In contrast, enforced activation of MEK/ERK signaling by expressing ectopic B-Raf (V600E) or constitutively activated MEK1 (MEK1-CA) or MEK2 (MEK2-CA) activated ERK and increased DR4 expression; these effects were inhibited when a MEK inhibitor was present. Promoter analysis through deletion and mutation identified the AP-1 binding site as an essential response element for enhancing DR4 transactivation by MEK1-CA. Furthermore, inhibition of AP-1 by c-Jun knockdown abrogated the ability of MEK1-CA to increase DR4 promoter activity and DR4 expression. These results suggest an essential role of AP-1 in mediating MEK/ERK activation-induced DR4 expression. Our findings together highlight a previously undiscovered mechanism that positively regulates DR4 expression through activation of the MEK/ERK/AP-1 signaling pathway. PMID:27576686

Comparative study of active plasma lenses in high-quality electron accelerator transport lines

NASA Astrophysics Data System (ADS)

van Tilborg, J.; Barber, S. K.; Benedetti, C.; Schroeder, C. B.; Isono, F.; Tsai, H.-E.; Geddes, C. G. R.; Leemans, W. P.

2018-05-01

Electrically discharged active plasma lenses (APLs) are actively pursued in compact high-brightness plasma-based accelerators due to their high-gradient, tunable, and radially symmetric focusing properties. In this manuscript, the APL is experimentally compared with a conventional quadrupole triplet, highlighting the favorable reduction in the energy dependence (chromaticity) in the transport line. Through transport simulations, it is explored how the non-uniform radial discharge current distribution leads to beam-integrated emittance degradation and a charge density reduction at focus. However, positioning an aperture at the APL entrance will significantly reduce emittance degradation without additional loss of charge in the high-quality core of the beam. An analytical model is presented that estimates the emittance degradation from a short beam driving a longitudinally varying wakefield in the APL. Optimizing laser plasma accelerator operation is discussed where emittance degradation from the non-uniform discharge current (favoring small beams inside the APL) and wakefield effects (favoring larger beam sizes) is minimized.

Comparative study of active plasma lenses in high-quality electron accelerator transport lines

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

van Tilborg, J.; Barber, S. K.; Benedetti, C.

Electrically discharged active plasma lenses (APLs) are actively pursued in compact high-brightness plasma-based accelerators due to their high-gradient, tunable, and radially symmetric focusing properties. In this paper, the APL is experimentally compared with a conventional quadrupole triplet, highlighting the favorable reduction in the energy dependence (chromaticity) in the transport line. Through transport simulations, it is explored how the non-uniform radial discharge current distribution leads to beam-integrated emittance degradation and a charge density reduction at focus. However, positioning an aperture at the APL entrance will significantly reduce emittance degradation without additional loss of charge in the high-quality core of the beam.more » An analytical model is presented that estimates the emittance degradation from a short beam driving a longitudinally varying wakefield in the APL. Finally, optimizing laser plasma accelerator operation is discussed where emittance degradation from the non-uniform discharge current (favoring small beams inside the APL) and wakefield effects (favoring larger beam sizes) is minimized.« less

Comparative study of active plasma lenses in high-quality electron accelerator transport lines

DOE PAGES

van Tilborg, J.; Barber, S. K.; Benedetti, C.; ...

2018-03-13

Electrically discharged active plasma lenses (APLs) are actively pursued in compact high-brightness plasma-based accelerators due to their high-gradient, tunable, and radially symmetric focusing properties. In this paper, the APL is experimentally compared with a conventional quadrupole triplet, highlighting the favorable reduction in the energy dependence (chromaticity) in the transport line. Through transport simulations, it is explored how the non-uniform radial discharge current distribution leads to beam-integrated emittance degradation and a charge density reduction at focus. However, positioning an aperture at the APL entrance will significantly reduce emittance degradation without additional loss of charge in the high-quality core of the beam.more » An analytical model is presented that estimates the emittance degradation from a short beam driving a longitudinally varying wakefield in the APL. Finally, optimizing laser plasma accelerator operation is discussed where emittance degradation from the non-uniform discharge current (favoring small beams inside the APL) and wakefield effects (favoring larger beam sizes) is minimized.« less

Induction of the high-affinity Na(+)-dependent glutamate transport system XAG- by hypertonic stress in the renal epithelial cell line NBL-1.

PubMed Central

Ferrer-Martinez, A; Felipe, A; Nicholson, B; Casado, J; Pastor-Anglada, M; McGivan, J

1995-01-01

The high-affinity Na(+)-dependent glutamate transport system XAG- is induced (threefold increase in Vmax. with no change in Km) by hypertonicity in the renal epithelial cell line NBL-1. This effect is dependent on protein synthesis and glycosylation and is accompanied by an increase in EAAC1 mRNA levels. Other Na(+)-dependent transport systems in this cell line do not respond to hypertonic stress. In contrast to recent findings [Ruiz-Montasell, Gomez-Angelats, Casado, Felipe, McGivan and Pastor-Anglada (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 9569-9573] showing that increased system A activity after hyperosmotic shock results from induction of a regulatory protein, this is the first demonstration that hypertonicity may increase the expression of the gene for an amino acid transport protein itself. Images Figure 4 PMID:7654212

Diadenosine polyphosphates (Ap3A and Ap4A) behave as alarmones triggering the synthesis of enzymes of the phenylpropanoid pathway in Arabidopsis thaliana.

PubMed

Pietrowska-Borek, Małgorzata; Nuc, Katarzyna; Zielezińska, Małgorzata; Guranowski, Andrzej

2011-12-01

It is known that cells under stress accumulate various dinucleoside polyphosphates, compounds suggested to function as alarmones. In plants, the phenylpropanoid pathways yield metabolites protecting these organisms against various types of stress. Observations reported in this communication link these two phenomena and provide an example of a metabolic "addressee" for an "alarm" signaled by diadenosine triphosphate (Ap3A) or diadenosine tetraphosphate (Ap4A). In response to added Ap3A or Ap4A, seedlings of Arabidopsis thaliana incubated in full nutrition medium increased both the expression of the genes for and the specific activity of phenylalanine ammonia-lyase and 4-coumarate:coenzyme A ligase, enzymes that control the beginning of the phenylpropanoid pathway. Neither adenine mononucleotides (AMP, ADP or ATP) nor adenosine evoked such effects. Reactions catalyzed in vitro by these enzymes were not affected by Ap3A or Ap4A.

Multipurpose active pixel sensor (APS)-based microtracker

NASA Astrophysics Data System (ADS)

Eisenman, Allan R.; Liebe, Carl C.; Zhu, David Q.

1998-12-01

A new, photon-sensitive, imaging array, the active pixel sensor (APS) has emerged as a competitor to the CCD imager for use in star and target trackers. The Jet Propulsion Laboratory (JPL) has undertaken a program to develop a new generation, highly integrated, APS-based, multipurpose tracker: the Programmable Intelligent Microtracker (PIM). The supporting hardware used in the PIM has been carefully selected to enhance the inherent advantages of the APS. Adequate computation power is included to perform star identification, star tracking, attitude determination, space docking, feature tracking, descent imaging for landing control, and target tracking capabilities. Its first version uses a JPL developed 256 X 256-pixel APS and an advanced 32-bit RISC microcontroller. By taking advantage of the unique features of the APS/microcontroller combination, the microtracker will achieve about an order-of-magnitude reduction in mass and power consumption compared to present state-of-the-art star trackers. It will also add the advantage of programmability to enable it to perform a variety of star, other celestial body, and target tracking tasks. The PIM is already proving the usefulness of its design concept for space applications. It is demonstrating the effectiveness of taking such an integrated approach in building a new generation of high performance, general purpose, tracking instruments to be applied to a large variety of future space missions.

Automated Plasma Spray (APS) process feasibility study

NASA Technical Reports Server (NTRS)

Fetheroff, C. W.; Derkacs, T.; Matay, I. M.

1981-01-01

An automated plasma spray (APS) process was developed to apply two layer (NiCrAlY and ZrO2-12Y2O3) thermal barrier coatings to aircraft and stationary gas turbine engine blade airfoils. The APS process hardware consists of four subsystems: a mechanical positioning subsystem incorporating two interlaced six degree of freedom assemblies (one for coating deposition and one for coating thickness monitoring); a noncoherent optical metrology subsystem (for in process gaging of the coating thickness buildup at specified points on the specimen); a microprocessor based adaptive system controller (to achieve the desired overall thickness profile on the specimen); and commerical plasma spray equipment. Over fifty JT9D first stage aircraft turbine blade specimens, ten W501B utility turbine blade specimens and dozens of cylindrical specimens were coated with the APS process in preliminary checkout and evaluation studies. The best of the preliminary turbine blade specimens achieved an overall coating thickness uniformity of 53 micrometers (2.1 mils), much better than is achievable manually. Comparative evaluations of coating thickness uniformity for manually sprayed and APS coated specimens were performed. One of the preliminary turbine blade evaluation specimens was subjected to a torch test and metallographic evaluation. Some cylindrical specimens coated with the APS process survived up to 2000 cycles in subsequent burner rig testing.

Army and Marine Corps Active Protection System (APS) Efforts

DTIC Science & Technology

2016-08-30

efforts—the Expedited, Non-Developmental Item (NDI) APS effort and the Modular Active Protection System (MAPS) effort. The Marines describe their...17 Modular Active Protection System (MAPS) Effort .......................................................... 18 The Marine Corps APS...Merkava Mark 4 tank was designed around the Trophy APS. 32 The Army’s Modular Active Protection System (MAPS) effort, described below, is intended to

Arachidonic Acid-Induced Expression of the Organic Solute and Steroid Transporter-beta (Ost-beta) in a Cartilaginous Fish Cell Line

PubMed Central

Hwang, Jae-Ho; Parton, Angela; Czechanski, Anne; Ballatori, Nazzareno; Barnes, David

2008-01-01

The organic solute and steroid transporter (OST/Ost) is a unique membrane transport protein heterodimer composed of subunits designated alpha and beta, that transports conjugated steroids and prostaglandin E2 across the plasma membrane. Ost was first identified in the liver of the cartilaginous fish Leucoraja erinacea, the little skate, and subsequently was found in many other species, including humans and rodents. The present study describes the isolation of a new cell line, LEE-1, derived from an early embryo of L. erinacea, and characterizes the expression of Ost in these cells. The mRNA size and amino acid sequence of Ost-beta in LEE-1 was identical to that previously reported for Ost-beta from skate liver, and the primary structure was identical to that of the spiny dogfish shark (Squalus acanthias) with the exception of a single amino acid. Ost-beta was found both on the plasma membrane and intracellularly in LEE-1 cells, consistent with its localization in other cell types. Interestingly, arachidonic acid, the precursor to eiconsanoids, strongly induced Ost-beta expression in LEE-1 cells and a lipid mixture containing arachidonic acid also induced Ost-alpha. Overall, the present study describes the isolation of a novel marine cell line, and shows that this cell line expresses relatively high levels of Ost when cultured in the presence of arachidonic acid. Although the function of this transport protein in embryo-derived cells is unknown, it may play a role in the disposition of eicosanoids or steroid-derived molecules. PMID:18407792

Gradient of the stellar magnetic field in measurements of hydrogen line cores

NASA Astrophysics Data System (ADS)

Kudryavtsev, Dimitry O.; Romanyuk, Iosif I.

2009-04-01

We report the observed systematic differences in longitudinal magnetic field values, obtained from measurements of metal lines and the core of the Hβ line for a number of Ap stars, having strong global magnetic fields. In overwhelming majority of cases the magnetic field values, obtained from measurements of hydrogen lines cores, is smaller then the ones obtained from metal lines. We discuss some possible explanations of this effect, the most probable of which is the existence of the gradient of the magnetic field in stellar atmospheres.

Bicarbonate-dependent chloride transport drives fluid secretion by the human airway epithelial cell line Calu-3

PubMed Central

Shan, Jiajie; Liao, Jie; Huang, Junwei; Robert, Renaud; Palmer, Melissa L; Fahrenkrug, Scott C; O'Grady, Scott M; Hanrahan, John W

2012-01-01

Anion and fluid secretion are both defective in cystic fibrosis (CF); however, the transport mechanisms are not well understood. In this study, Cl− and HCO3− secretion was measured using genetically matched CF transmembrane conductance regulator (CFTR)-deficient and CFTR-expressing cell lines derived from the human airway epithelial cell line Calu-3. Forskolin stimulated the short-circuit current (Isc) across voltage-clamped monolayers, and also increased the equivalent short-circuit current (Ieq) calculated under open-circuit conditions. Isc was equivalent to the HCO3− net flux measured using the pH-stat technique, whereas Ieq was the sum of the Cl− and HCO3− net fluxes. Ieq and HCO3− fluxes were increased by bafilomycin and ZnCl2, suggesting that some secreted HCO3− is neutralized by parallel electrogenic H+ secretion. Ieq and fluid secretion were dependent on the presence of both Na+ and HCO3−. The carbonic anhydrase inhibitor acetazolamide abolished forskolin stimulation of Ieq and HCO3− secretion, suggesting that HCO3− transport under these conditions requires catalysed synthesis of carbonic acid. Cl− was the predominant anion in secretions under all conditions studied and thus drives most of the fluid transport. Nevertheless, 50–70% of Cl− and fluid transport was bumetanide-insensitive, suggesting basolateral Cl− loading by a sodium–potassium–chloride cotransporter 1 (NKCC1)-independent mechanism. Imposing a transepithelial HCO3− gradient across basolaterally permeabilized Calu-3 cells sustained a forskolin-stimulated current, which was sensitive to CFTR inhibitors and drastically reduced in CFTR-deficient cells. Net HCO3− secretion was increased by bilateral Cl− removal and therefore did not require apical Cl−/HCO3− exchange. The results suggest a model in which most HCO3− is recycled basolaterally by exchange with Cl−, and the resulting HCO3−-dependent Cl− transport provides an osmotic driving force for

ARF1·GTP, Tyrosine-based Signals, and Phosphatidylinositol 4,5-Bisphosphate Constitute a Minimal Machinery to Recruit the AP-1 Clathrin Adaptor to Membranes

PubMed Central

Crottet, Pascal; Meyer, Daniel M.; Rohrer, Jack; Spiess, Martin

2002-01-01

At the trans-Golgi network, clathrin coats containing AP-1 adaptor complexes are formed in an ARF1-dependent manner, generating vesicles transporting cargo proteins to endosomes. The mechanism of site-specific targeting of AP-1 and the role of cargo are poorly understood. We have developed an in vitro assay to study the recruitment of purified AP-1 adaptors to chemically defined liposomes presenting peptides corresponding to tyrosine-based sorting motifs. AP-1 recruitment was found to be dependent on myristoylated ARF1, GTP or nonhydrolyzable GTP-analogs, tyrosine signals, and small amounts of phosphoinositides, most prominently phosphatidylinositol 4,5-bisphosphate, in the absence of any additional cytosolic or membrane bound proteins. AP-1 from cytosol could be recruited to a tyrosine signal independently of the lipid composition, but the rate of recruitment was increased by phosphatidylinositol 4,5-bisphosphate. The results thus indicate that cargo proteins are involved in coat recruitment and that the local lipid composition contributes to specifying the site of vesicle formation. PMID:12388765

The magnetic fields of Ap stars from high resolution Stokes IQUV spectropolarimetry

NASA Astrophysics Data System (ADS)

Silvester, James

In this thesis we describe the acquisition of high resolution time resolved spectropolarimetric observations of 7 (bright and well understood) Ap stars in Stokes IQUV using the ESPaDOnS and Narval spectropolarimeters at the Canada-France-Hawaii Telescope and the 2m Telescope Bernard Lyot at Pic du Midi Observatory. We compare these observations with those obtained a decade earlier using the MuSiCoS spectropolarimeter to confirm consistency with the older data and provide evidence that both ESPaDOnS and Narval perform as expected in all Stokes parameters. We demonstrate that our refined longitudinal magnetic field and linear polarisation measurements for these 7 stars are of much greater quality than was previously obtained with MuSiCoS and that the global magnetic properties of these stars are stable over a long timescale. The ultimate aim of these new data is to provide a basis from which mapping of both the magnetic field and abundance structures can be performed on our target stars. We then describe magnetic field mapping of the Ap star alpha 2 CVn using these data. This mapping is achieved with the use of tomographic inversion of Doppler-broadened Stokes IQUV profiles of a large variety of spectral lines using the INVERS10 Magnetic Doppler imaging code. We show that not only are the new magnetic field maps of alpha 2 CVn consistent with a previous generation of maps of alpha 2 CVn, but that the same magnetic field topology can be derived from a variety of atomic line sets. This indicates that the magnetic field we derive for alpha2 CVn is a realistic representation of the star's true magnetic topology. Finally we investigate surface abundance structures for alpha 2 CVn for various chemical elements. We investigate the correlation between the location of these abundance features and the magnetic field of alpha 2 CVn. We will demonstrate that whilst the magnetic field plays a role in the formation of abundance structures, the current theoretical framework does

Heparin (GAG-hed) inhibits LCR activity of human papillomavirus type 18 by decreasing AP1 binding.

PubMed

Villanueva, Rita; Morales-Peza, Néstor; Castelán-Sánchez, Irma; García-Villa, Enrique; Tapia, Rocio; Cid-Arregui, Angel; García-Carrancá, Alejandro; López-Bayghen, Esther; Gariglio, Patricio

2006-08-31

High risk HPVs are causative agents of anogenital cancers. Viral E6 and E7 genes are continuously expressed and are largely responsible for the oncogenic activity of these viruses. Transcription of the E6 and E7 genes is controlled by the viral Long Control Region (LCR), plus several cellular transcription factors including AP1 and the viral protein E2. Within the LCR, the binding and activity of the transcription factor AP1 represents a key regulatory event in maintaining E6/E7 gene expression and uncontrolled cell proliferation. Glycosaminoglycans (GAGs), such as heparin, can inhibit tumour growth; they have also shown antiviral effects and inhibition of AP1 transcriptional activity. The purpose of this study was to test the heparinoid GAG-hed, as a possible antiviral and antitumoral agent in an HPV18 positive HeLa cell line. Using in vivo and in vitro approaches we tested GAG-hed effects on HeLa tumour cell growth, cell proliferation and on the expression of HPV18 E6/E7 oncogenes. GAG-hed effects on AP1 binding to HPV18-LCR-DNA were tested by EMSA. We were able to record the antitumoral effect of GAG-hed in vivo by using as a model tumours induced by injection of HeLa cells into athymic female mice. The antiviral effect of GAG-hed resulted in the inhibition of LCR activity and, consequently, the inhibition of E6 and E7 transcription. A specific diminishing of cell proliferation rates was observed in HeLa but not in HPV-free colorectal adenocarcinoma cells. Treated HeLa cells did not undergo apoptosis but the percentage of cells in G2/M phase of the cell cycle was increased. We also detected that GAG-hed prevents the binding of the transcription factor AP1 to the LCR. Direct interaction of GAG-hed with the components of the AP1 complex and subsequent interference with its ability to correctly bind specific sites within the viral LCR may contribute to the inhibition of E6/E7 transcription and cell proliferation. Our data suggest that GAG-hed could have antitumoral

Induction of dystrophin Dp71 expression during neuronal differentiation: opposite roles of Sp1 and AP2alpha in Dp71 promoter activity.

PubMed

Morales-Lázaro, Sara Luz; González-Ramírez, Ricardo; Gómez, Pablo; Tapia-Ramírez, Victor; de León, Mario Bermúdez; Cisneros, Bulmaro

2010-01-01

In this study, we delineated the molecular mechanisms that modulate Dp71 expression during neuronal differentiation, using the N1E-115 cell line. We demonstrated that Dp71 expression is up-regulated in response to cAMP-mediated neuronal differentiation of these cells, and that this induction is controlled at promoter level. Functional deletion analysis of the Dp71 promoter revealed that a 5'-flanking 159-bp DNA fragment that contains Sp1 and AP2 binding sites is necessary and sufficient for basal expression of this TATA-less promoter, as well as for its induction during neuronal differentiation. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that Sp1 and AP2alpha bind to their respective DNA elements within the Dp71 basal promoter. Overall, mutagenesis assays on the Sp1 and AP2 binding sites, over-expression of Sp1 and AP2alpha, as well as knock-down experiments on Sp1 and AP2alpha gene expression established that Dp71 basal expression is controlled by the combined action of Sp1 and AP2alpha, which act as activator and repressor, respectively. Furthermore, we demonstrated that induction of Dp71 expression in differentiated cells is the result of the maintenance of positive regulation exerted by Sp1, as well as of the loss of AP2alpha binding, which ultimately releases the promoter from repression.

Neuronal Activity and the Expression of Clathrin Assembly Protein AP180

PubMed Central

Wu, Fangbai; Mattson, Mark P.; Yao, Pamela J.

2010-01-01

The clathrin assembly protein AP180 is known to promote the assembly of clathrin-coated vesicles in the neuron. However, it is unknown whether the expression of AP180 is influenced by neuronal activity. In this study, we report that chronic depolarization results in a reduction of AP180 from hippocampal neurons, while acute depolarization causes a dispersed synaptic distribution of AP180. Activity-induced effects are observed only for AP180, but not for the structurally-related clathrin assembly proteins CALM, epsin1, or HIP1. These findings suggest that AP180 levels and synaptic distribution are highly sensitive to neuronal activity. PMID:20937255

Observing Infrared Emission Lines of Neutron-Capture Species in Planetary Nebulae: New Detections with IGRINS

NASA Astrophysics Data System (ADS)

Dinerstein, Harriet L.; Sterling, N. C.; Kaplan, Kyle F.; Bautista, Manuel A.

2015-08-01

As the former envelopes of evolved stars, planetary nebulae (PNe) present an opportunity to study slow neutron-capture reactions (the “s-process”) during the AGB. Such studies differ from those of AGB stars in two ways. First, PNe represent the end point of self-enrichment and dredge-up in the star and most of its mass return to the ISM, enabling us to infer the nucleosynthetic yield of a specific element. Second, some s-process products are observable in PNe but difficult or impossible to observe in cool stars. These include some species with nuclear charge Z in the 30’s for which the major synthesis sites are uncertain. Optical emission lines of trans-iron species have been observed in some PNe, but are faint and can suffer from blending with lines of more abundant elements (Péquignot & Baluteau 1994, A&A, 283, 593; Sharpee et al. 2007, ApJ, 659, 1265). Observing infrared transitions from low energy states has proven to be a fruitful alternate approach. We used K-band lines of Se (Z=34) and Kr (Z=36) to study the demographics of their abundances in a large sample of Milky Way PNe (Dinerstein 2001, ApJ, 550, L223; Sterling & Dinerstein 2008, ApJ, 174, 158; Sterling, Porter, & Dinerstein 2015, submitted). An L-band emission line of Zn identified by Dinerstein & Geballe (2001, ApJ, 562, 515) and further observed by Smith, Zijlstra, & Dinerstein 2014 (MNRAS, 441, 3161), can be used as a tracer of the Fe-group, enabling determinations of the key stellar population diagnostic ratio [alpha/Fe] in PNe (see poster by Dinerstein et al., Focus Meeting 4). Using IGRINS, a high spectral resolution H and K band spectrometer (Park & Jaffe et al. 2014, Proc SPIE, 9147), we have discovered several new lines not previously reported in any astronomical object. Our detection of an H-band line of Rb (Z=37) confirms previous claims of optical Rb detections and indicates enrichment by a factor of ~4 in the PN NGC 7027 (Sterling, Dinerstein, Kaplan, & Bautista, in preparation

AccuNet/AP (Associated Press) Multimedia Archive

ERIC Educational Resources Information Center

Young, Terrence E., Jr.

2004-01-01

The AccuNet/AP Multimedia Archive is an electronic library containing the AP's current photos and a selection of pictures from their enormous print and negative library, as well as text and graphic material. It is composed of two photo databases as well as graphics, text, and audio databases. The features of this database are briefly described in…

Quantitative assessment of direct and indirect landslide risk along transportation lines in southern India

NASA Astrophysics Data System (ADS)

Jaiswal, P.; van Westen, C. J.; Jetten, V.

2010-06-01

A quantitative approach for landslide risk assessment along transportation lines is presented and applied to a road and a railway alignment in the Nilgiri hills in southern India. The method allows estimating direct risk affecting the alignments, vehicles and people, and indirect risk resulting from the disruption of economic activities. The data required for the risk estimation were obtained from historical records. A total of 901 landslides were catalogued initiating from cut slopes along the railway and road alignment. The landslides were grouped into three magnitude classes based on the landslide type, volume, scar depth, run-out distance, etc and their probability of occurrence was obtained using frequency-volume distribution. Hazard, for a given return period, expressed as the number of landslides of a given magnitude class per kilometre of cut slopes, was obtained using Gumbel distribution and probability of landslide magnitude. In total 18 specific hazard scenarios were generated using the three magnitude classes and six return periods (1, 3, 5, 15, 25, and 50 years). The assessment of the vulnerability of the road and railway line was based on damage records whereas the vulnerability of different types of vehicles and people was subjectively assessed based on limited historic incidents. Direct specific loss for the alignments (railway line and road), vehicles (train, bus, lorry, car and motorbike) was expressed in monetary value (US), and direct specific loss of life of commuters was expressed in annual probability of death. Indirect specific loss (US) derived from the traffic interruption was evaluated considering alternative driving routes, and includes losses resulting from additional fuel consumption, additional travel cost, loss of income to the local business, and loss of revenue to the railway department. The results indicate that the total loss, including both direct and indirect loss, from 1 to 50 years return period, varies from US 90 840 to US

LaAP2L1, a heterosis-associated AP2/EREBP transcription factor of Larix, increases organ size and final biomass by affecting cell proliferation in Arabidopsis.

PubMed

Li, Ai; Zhou, Yanan; Jin, Chuan; Song, Wenqin; Chen, Chengbin; Wang, Chunguo

2013-11-01

In Larix and in some crops, heterosis is prevalent and has been widely used in breeding to produce excellent varieties. However, the molecular basis of heterosis in Larix remains ambiguous. LaAP2L1, a member of the AP2/EREBP transcription factor family, has been suggested to be involved in heterosis in Larix hybrids. Here, the function and regulation of LaAP2L1 were further explored. Overexpression of LaAP2L1 led to markedly enlarged organs and heterosis-like traits in Arabidopsis. Fresh weight of leaves was almost twice as great as in vector controls. Likewise, seed yield of 35S::LaAP2L1 individual plants was >200% greater than that of control plants. The enlarged organs and heterosis-like traits displayed by 35S::LaAP2L1 plants were mainly due to enhanced cell proliferation and prolonged growth duration. At the molecular level, LaAP2L1 upregulated the expression of ANT, EBP1, and CycD3;1 and inhibited the expression of ARGOS in 35S::LaAP2L1 plants, suggesting an important molecular role of LaAP2L1 in regulating plant organ development. These findings provide new insights into the formation of heterosis in woody plants and suggest that LaAP2L1 has potential applications in breeding high-yielding crops and energy plants. In addition, 50 AP2/EREBP transcription factors, including LaAP2L1, in Larix were identified by transcriptome sequencing, and phylogenetic analysis was conducted. This provided information that will be important in further revealing the functions of these transcription factors.

The APS in Public Affairs

NASA Astrophysics Data System (ADS)

Lustig, Harry

2000-04-01

Although the American Physical Society was created for the interchange of scientific ideas, the call to the founding meeting included the observation that the organization "could not fail to have an important influence in all matters affecting the interest of physicists". However for most of its history APS did not behave like "just another interest group in American society". Instead, at the beginning, it limited itself to such successful initiatives as the creation of the Bureau of Standards and such unsuccessful ones as adoption of the metric system. After World War II, speaking out on behalf of the freedom of science and scientists, such as Astin, Condon, and Oppenheimer, became important. In the 1970's, pushed by members, the Society became more "political", sponsoring sessions and studies on defense issues, taking a stand for the Equal Rights Amendment and creating the Panel on Public Affairs and the Forum on Physics and Society. Only in the last fifteen years has the APS unabashedly lobbied for the economic interests of physics and physicists. Adopting this new, if unavoidable role may have unintended consequences for the willingness and effectiveness of APS in speaking out on other public issues.

Influence of diadenosine tetraphosphate (Ap4A) on lipid metabolism.

PubMed

Rüsing, D; Verspohl, E J

2004-01-01

Diadenosine polyphosphates (Ap(x)A) are physiologically released and may be partly involved in the pathogenesis of diabetes mellitus. Ap(4)A (diadenosine tetraphosphate) leads to an increase in blood glucose while it decreases insulin levels in plasma. A possible link between Ap(x)A and diabetes mellitus-associated diseases such as insulin resistance and hyperlipidemia (plasma free fatty acids, cholesterol and its biosynthesis, triacylglycerols) has not been investigated yet. Parameters such as free fatty acid and cholesterol content in blood were determined enzymically. The biosynthesis of cholesterol and triacylglycerols was determined in HepG2 cells using the radioactive precursor [(14)C]-acetate and by using gas chromatography. Plasma free fatty acids were significantly decreased 5 and 10 min after an Ap(4)A bolus (0.75 mg kg(-1) b.w.) given to rats. Plasma cholesterol was reduced 5 and 60 min after Ap(4)A administration. LPDS (lipoprotein-deficient serum)-stimulated cholesterol biosynthesis in HepG2 cells was significantly reduced after 1 h incubation with Ap(4)A. Triacylglycerol (TAG) biosynthesis in HepG2 cells was not significantly influenced by Ap(4)A; there was just a tendency for a concentration-dependent decrease in TAG levels. In conclusion Ap(4)A as a diabetogenetic compound is not likely to be responsible for the development of insulin resistance or of hyperlipidemia. Parameters such as free fatty acids, cholesterol and triacylglycerols are not elevated by Ap(4)A, but are even decreased. Ap(4)A seems to be involved in the development of diabetes mellitus by increasing blood glucose and decreasing plasma insulin as shown earlier, but not in diabetes mellitus-associated diseases such as insulin resistance or hyperlipidemia.

Diadenosine tetraphosphate (Ap4A) inhibits ATP-induced excitotoxicity: a neuroprotective strategy for traumatic spinal cord injury treatment.

PubMed

Reigada, David; Navarro-Ruiz, Rosa María; Caballero-López, Marcos Javier; Del Águila, Ángela; Muñoz-Galdeano, Teresa; Maza, Rodrigo M; Nieto-Díaz, Manuel

2017-03-01

Reducing cell death during the secondary injury is a major priority in the development of a cure for traumatic spinal cord injury (SCI). One of the earliest processes that follow SCI is the excitotoxicity resulting from the massive release of excitotoxicity mediators, including ATP, which induce an excessive and/or prolonged activation of their receptors and a deregulation of the calcium homeostasis. Diadenosine tetraphosphate (Ap 4 A) is an endogenous purinergic agonist, present in both extracellular and intracellular fluids, with promising cytoprotective effects in different diseases including neurodegenerative processes. In a search for efficient neuroprotective strategies for SCI, we have tested the capability of Ap 4 A to reduce the excitotoxic death mediated by the ATP-induced deregulation of calcium homeostasis and its consequences on tissue preservation and functional recovery in a mouse model of moderate contusive SCI. Our analyses with the murine neural cell line Neuro2a demonstrate that treatment with Ap 4 A reduces ATP-dependent excitotoxic death by both lowering the intracellular calcium response and decreasing the expression of specific purinergic receptors. Follow-up analyses in a mouse model of contusive SCI showed that acute administration of Ap 4 A following SCI reduces tissue damage and improves motor function recovery. These results suggest that Ap 4 A cytoprotection results from a decrease of the purinergic tone preventing the effects of a massive release of ATP after SCI, probably together with a direct induction of anti-apoptotic and pro-survival pathways via activation of P2Y 2 proposed in previous studies. In conclusion, Ap 4 A may be a good candidate for an SCI therapy, particularly to reduce excitotoxicity in combination with other modulators and/or inhibitors of the excitotoxic process that are being tested.

Downregulation of peptide transporter genes in cell lines transformed with the highly oncogenic adenovirus 12

PubMed Central

1994-01-01

The expression of class I major histocompatibility complex antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low, and correlates with the high oncogenicity of this virus. In primary embryonal fibroblasts from transgenic mice that express both endogenous H-2 genes and a miniature swine class I gene (PD1), Ad12- mediated transformation results in suppression of cell surface expression of all class I antigens. Although class I mRNA levels of PD1 and H-2Db are similar to those in nonvirally transformed cells, recognition of newly synthesized class I molecules by a panel of monoclonal antibodies is impaired, presumably as a result of inefficient assembly and transport of the class I molecules. Class I expression can be partially induced by culturing cells at 26 degrees C, or by coculture of cells with class I binding peptides at 37 degrees C. Analysis of steady state mRNA levels of the TAP1 and TAP2 transporter genes for Ad12-transformed cell lines revealed that they both are significantly reduced, TAP2 by about 100-fold and TAP1 by 5-10-fold. Reconstitution of PD1 and H-2Db, but not H-2Kb, expression is achieved in an Ad12-transformed cell line by stable transfection with a TAP2, but not a TAP1, expression construct. From these data it may be concluded that suppressed expression of peptide transporter genes, especially TAP2, in Ad12-transformed cells inhibits cell surface expression of class I molecules. The failure to fully reconstitute H- 2Db and H-2Kb expression indicates that additional factors are involved in controlling class I gene expression in Ad12-transformed cells. Nevertheless, these results suggest that suppression of peptide transporter genes might be an important mechanism whereby virus- transformed cells escape immune recognition in vivo. PMID:7519239

Final report for tank 241-AP-108, grab samples 8AP-96-1, 8AP-96-2 and 8AP-96-FB

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

Esch, R.A.

1996-04-19

This document is the final report deliverable for the tank 241-AP-108 grab samples. The samples were subsampled and analyzed in accordance with the TSAP. Included in this report are the results for the Waste Compatibility analyses, with the exception of DSC and thermogravimetric analysis (TGA) results which were presented in the 45 Day report (Part 2 of this document). The raw data for all analyses, with the exception of DSC and TGA, are also included in this report.

Predictive Validity Study of the APS Writing and Reading Tests [and] Validating Placement Rules for the APS Writing Test.

ERIC Educational Resources Information Center

College of the Canyons, Valencia, CA. Office of Institutional Development.

California's College of the Canyons has used the College Board Assessment and Placement Services (APS) test to assess students' abilities in basic and college English since spring 1993. These two reports summarize data from a May 1994 study of the predictive validity of the APS writing and reading tests and a June 1994 effort to validate the cut…

Noble internal transport barriers and radial subdiffusion of toroidal magnetic lines

NASA Astrophysics Data System (ADS)

Misguich, J. H.; Reuss, J.-D.; Constantinescu, D.; Steinbrecher, G.; Vlad, M.; Spineanu, F.; Weyssow, B.; Balescu, R.

2003-11-01

Internal transport barriers (ITB's) observed in tokamaks are described by a purely magnetic approach. Magnetic line motion in toroidal geometry with broken magnetic surfaces is studied from a previously derived Hamiltonian map in situation of incomplete chaos. This appears to reproduce in a realistic way the main features of a tokamak, for a given safety factor profile and in terms of a single parameter L representing the amplitude of the magnetic perturbation. New results are given concerning the Shafranov shift as function of L. The phase space (psi ,θ ) of the "tokamap" describes the poloidal section of the line trajectories, where psi is the toroidal flux labelling the surfaces. For small values of L, closed magnetic surfaces exist (KAM tori) and island chains begin to appear on rational surfaces for higher values of L, with chaotic zones around hyperbolic points, as expected. Island remnants persist in the chaotic domain for all relevant values of L at the main rational q-values. Single trajectories of magnetic line motion indicate the persistence of a central protected plasma core, surrounded by a chaotic shell enclosed in a double-sided transport barrier: the latter is identified as being composed of two Cantori located on two successive “most-noble” numbers values of the perturbed safety factor, and forming an internal transport barrier (ITB). Magnetic lines which succeed to escape across this barrier begin to wander in a wide chaotic sea extending up to a very robust barrier (as long as Lprecsim 1) which is identified mathematically as a robust KAM surface at the plasma edge. In this case the motion is shown to be intermittent, with long stages of pseudo-trapping in the chaotic shell, or of sticking around island remnants, as expected for a continuous time random walk. For values of Lsucceq 1, above the escape threshold, most magnetic lines succeed to escape out of the external barrier which has become a permeable Cantorus. Statistical analysis of a

CoGAPS matrix factorization algorithm identifies transcriptional changes in AP-2alpha target genes in feedback from therapeutic inhibition of the EGFR network

PubMed Central

Thakar, Manjusha; Howard, Jason D.; Kagohara, Luciane T.; Krigsfeld, Gabriel; Ranaweera, Ruchira S.; Hughes, Robert M.; Perez, Jimena; Jones, Siân; Favorov, Alexander V.; Carey, Jacob; Stein-O'Brien, Genevieve; Gaykalova, Daria A.; Ochs, Michael F.; Chung, Christine H.

2016-01-01

Patients with oncogene driven tumors are treated with targeted therapeutics including EGFR inhibitors. Genomic data from The Cancer Genome Atlas (TCGA) demonstrates molecular alterations to EGFR, MAPK, and PI3K pathways in previously untreated tumors. Therefore, this study uses bioinformatics algorithms to delineate interactions resulting from EGFR inhibitor use in cancer cells with these genetic alterations. We modify the HaCaT keratinocyte cell line model to simulate cancer cells with constitutive activation of EGFR, HRAS, and PI3K in a controlled genetic background. We then measure gene expression after treating modified HaCaT cells with gefitinib, afatinib, and cetuximab. The CoGAPS algorithm distinguishes a gene expression signature associated with the anticipated silencing of the EGFR network. It also infers a feedback signature with EGFR gene expression itself increasing in cells that are responsive to EGFR inhibitors. This feedback signature has increased expression of several growth factor receptors regulated by the AP-2 family of transcription factors. The gene expression signatures for AP-2alpha are further correlated with sensitivity to cetuximab treatment in HNSCC cell lines and changes in EGFR expression in HNSCC tumors with low CDKN2A gene expression. In addition, the AP-2alpha gene expression signatures are also associated with inhibition of MEK, PI3K, and mTOR pathways in the Library of Integrated Network-Based Cellular Signatures (LINCS) data. These results suggest that AP-2 transcription factors are activated as feedback from EGFR network inhibition and may mediate EGFR inhibitor resistance. PMID:27650546

AP Physics 1 & 2; Some Things Old and Some Things New

NASA Astrophysics Data System (ADS)

Morse, Robert

2015-04-01

In fall September 2014, AP Physics 1 and AP Physics 2 replaced the AP Physics B curriculum, with the first exams in the new courses coming up in May 2015. In this talk I will give an overview of the history and rationale for the changes, describe the process of developing the new Curriculum Framework, discuss changes in emphasis compared to AP Physics B, including the emphasis on laboratory work. Finally, I will give examples of the difference in the style of the questions to be used in the new AP exams.

Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells.

PubMed

Mahata, Sutapa; Bharti, Alok C; Shukla, Shirish; Tyagi, Abhishek; Husain, Syed A; Das, Bhudev C

2011-04-15

Specific types of high risk Human papillomaviruses (HR-HPVs) particularly, HPV types 16 and 18 cause cervical cancer and while the two recently developed vaccines against these HPV types are prophylactic in nature, therapeutic options for treatment and management of already existing HPV infection are not available as yet. Because transcription factor, Activator Protein-1 (AP-1) plays a central role in HPV-mediated cervical carcinogenesis, we explored the possibility of its therapeutic targeting by berberine, a natural alkaloid derived from a medicinal plant species, Berberis which has been shown to possess anti-inflammatory and anti-cancer properties with no known toxicity; however, the effect of berberine against HPV has not been elucidated. We studied the effect of berberine on HPV16-positive cervical cancer cell line, SiHa and HPV18-positive cervical cancer cell line, HeLa using electrophoretic mobility gel shift assays, western and northern blotting which showed that berberine could selectively inhibit constitutively activated AP-1 in a dose- and time-dependent manner and downregulates HPV oncogenes expression. Inhibition of AP-1 was also accompanied by changes in the composition of their DNA-binding complex. Berberine specifically downregulated expression of oncogenic c-Fos which was also absent in the AP-1 binding complex. Treatment with berberine resulted in repression of E6 and E7 levels and concomitant increase in p53 and Rb expression in both cell types. Berberine also suppressed expression of telomerase protein, hTERT, which translated into growth inhibition of cervical cancer cells. Interestingly, a higher concentration of berberine was found to reduce the cell viability through mitochondria-mediated pathway and induce apoptosis by activating caspase-3. These results indicate that berberine can effectively target both the host and viral factors responsible for development of cervical cancer through inhibition of AP-1 and blocking viral oncoproteins E6

Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells

PubMed Central

2011-01-01

Background- Specific types of high risk Human papillomaviruses (HR-HPVs) particularly, HPV types 16 and 18 cause cervical cancer and while the two recently developed vaccines against these HPV types are prophylactic in nature, therapeutic options for treatment and management of already existing HPV infection are not available as yet. Because transcription factor, Activator Protein-1 (AP-1) plays a central role in HPV-mediated cervical carcinogenesis, we explored the possibility of its therapeutic targeting by berberine, a natural alkaloid derived from a medicinal plant species, Berberis which has been shown to possess anti-inflammatory and anti-cancer properties with no known toxicity; however, the effect of berberine against HPV has not been elucidated. Results- We studied the effect of berberine on HPV16-positive cervical cancer cell line, SiHa and HPV18-positive cervical cancer cell line, HeLa using electrophoretic mobility gel shift assays, western and northern blotting which showed that berberine could selectively inhibit constitutively activated AP-1 in a dose- and time-dependent manner and downregulates HPV oncogenes expression. Inhibition of AP-1 was also accompanied by changes in the composition of their DNA-binding complex. Berberine specifically downregulated expression of oncogenic c-Fos which was also absent in the AP-1 binding complex. Treatment with berberine resulted in repression of E6 and E7 levels and concomitant increase in p53 and Rb expression in both cell types. Berberine also suppressed expression of telomerase protein, hTERT, which translated into growth inhibition of cervical cancer cells. Interestingly, a higher concentration of berberine was found to reduce the cell viability through mitochondria-mediated pathway and induce apoptosis by activating caspase-3. Conclusion- These results indicate that berberine can effectively target both the host and viral factors responsible for development of cervical cancer through inhibition of AP-1 and

A CoAP-Based Network Access Authentication Service for Low-Power Wide Area Networks: LO-CoAP-EAP.

PubMed

Garcia-Carrillo, Dan; Marin-Lopez, Rafael; Kandasamy, Arunprabhu; Pelov, Alexander

2017-11-17

The Internet-of-Things (IoT) landscape is expanding with new radio technologies. In addition to the Low-Rate Wireless Personal Area Network (LR-WPAN), the recent set of technologies conforming the so-called Low-Power Wide Area Networks (LP-WAN) offers long-range communications, allowing one to send small pieces of information at a reduced energy cost, which promotes the creation of new IoT applications and services. However, LP-WAN technologies pose new challenges since they have strong limitations in the available bandwidth. In general, a first step prior to a smart object being able to gain access to the network is the process of network access authentication. It involves authentication, authorization and key management operations. This process is of vital importance for operators to control network resources. However, proposals for managing network access authentication in LP-WAN are tailored to the specifics of each technology, which could introduce interoperability problems in the future. In this sense, little effort has been put so far into providing a wireless-independent solution for network access authentication in the area of LP-WAN. To fill this gap, we propose a service named Low-Overhead CoAP-EAP (LO-CoAP-EAP), which is based on previous work designed for LR-WPAN. LO-CoAP-EAP integrates the use of Authentication, Authorization and Accounting (AAA) infrastructures and the Extensible Authentication Protocol (EAP) protocol. For this integration, we use the Constrained Application Protocol (CoAP) to design a network authentication service independent of the type of LP-WAN technology. LO-CoAP-EAP represents a trade-off between flexibility, wireless technology independence, scalability and performance in LP-WAN.

A CoAP-Based Network Access Authentication Service for Low-Power Wide Area Networks: LO-CoAP-EAP

PubMed Central

Garcia-Carrillo, Dan; Marin-Lopez, Rafael; Kandasamy, Arunprabhu; Pelov, Alexander

2017-01-01

The Internet-of-Things (IoT) landscape is expanding with new radio technologies. In addition to the Low-Rate Wireless Personal Area Network (LR-WPAN), the recent set of technologies conforming the so-called Low-Power Wide Area Networks (LP-WAN) offers long-range communications, allowing one to send small pieces of information at a reduced energy cost, which promotes the creation of new IoT applications and services. However, LP-WAN technologies pose new challenges since they have strong limitations in the available bandwidth. In general, a first step prior to a smart object being able to gain access to the network is the process of network access authentication. It involves authentication, authorization and key management operations. This process is of vital importance for operators to control network resources. However, proposals for managing network access authentication in LP-WAN are tailored to the specifics of each technology, which could introduce interoperability problems in the future. In this sense, little effort has been put so far into providing a wireless-independent solution for network access authentication in the area of LP-WAN. To fill this gap, we propose a service named Low-Overhead CoAP-EAP (LO-CoAP-EAP), which is based on previous work designed for LR-WPAN. LO-CoAP-EAP integrates the use of Authentication, Authorization and Accounting (AAA) infrastructures and the Extensible Authentication Protocol (EAP) protocol. For this integration, we use the Constrained Application Protocol (CoAP) to design a network authentication service independent of the type of LP-WAN technology. LO-CoAP-EAP represents a trade-off between flexibility, wireless technology independence, scalability and performance in LP-WAN. PMID:29149040

Analysis of TFAP2A mutations in Branchio-Oculo-Facial Syndrome indicates functional complexity within the AP-2α DNA-binding domain

PubMed Central

Li, Hong; Sheridan, Ryan; Williams, Trevor

2013-01-01

Multiple lines of evidence indicate that the AP-2 transcription factor family has an important regulatory function in human craniofacial development. Notably, mutations in TFAP2A, the gene encoding AP-2α, have been identified in patients with Branchio-Oculo-Facial Syndrome (BOFS). BOFS is an autosomal-dominant trait that commonly presents with facial clefting, eye defects and branchial skin anomalies. Examination of multiple cases has suggested either simple haploinsufficiency or more complex genetic causes for BOFS, especially as the clinical manifestations are variable, with no clear genotype–phenotype correlation. Mutations occur throughout TFAP2A, but mostly within conserved sequences within the DNA contact domain of AP-2α. However, the consequences of the various mutations for AP-2α protein function have not been evaluated. Therefore, it remains unclear if all BOFS mutations result in similar changes to the AP-2α protein or if they each produce specific alterations that underlie the spectrum of phenotypes. Here, we have investigated the molecular consequences of the mutations that localize to the DNA-binding region. We show that although individual mutations have different effects on DNA binding, they all demonstrate significantly reduced transcriptional activities. Moreover, all mutant derivatives have an altered nuclear:cytoplasmic distribution compared with the predominantly nuclear localization of wild-type AP-2α and several can exert a dominant-negative activity on the wild-type AP-2α protein. Overall, our data suggest that the individual TFAP2A BOFS mutations can generate null, hypomorphic or antimorphic alleles and that these differences in activity, combined with a role for AP-2α in epigenetic events, may influence the resultant pathology and the phenotypic variability. PMID:23578821

NECAPs are negative regulators of the AP2 clathrin adaptor complex

PubMed Central

Beacham, Gwendolyn M; Partlow, Edward A; Lange, Jeffrey J

2018-01-01

Eukaryotic cells internalize transmembrane receptors via clathrin-mediated endocytosis, but it remains unclear how the machinery underpinning this process is regulated. We recently discovered that membrane-associated muniscin proteins such as FCHo and SGIP initiate endocytosis by converting the AP2 clathrin adaptor complex to an open, active conformation that is then phosphorylated (Hollopeter et al., 2014). Here we report that loss of ncap-1, the sole C. elegans gene encoding an adaptiN Ear-binding Coat-Associated Protein (NECAP), bypasses the requirement for FCHO-1. Biochemical analyses reveal AP2 accumulates in an open, phosphorylated state in ncap-1 mutant worms, suggesting NECAPs promote the closed, inactive conformation of AP2. Consistent with this model, NECAPs preferentially bind open and phosphorylated forms of AP2 in vitro and localize with constitutively open AP2 mutants in vivo. NECAPs do not associate with phosphorylation-defective AP2 mutants, implying that phosphorylation precedes NECAP recruitment. We propose NECAPs function late in endocytosis to inactivate AP2. PMID:29345618

49 CFR 195.410 - Line markers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Line markers. 195.410 Section 195.410 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF HAZARDOUS LIQUIDS BY...

Structural model of FeoB, the iron transporter from Pseudomonas aeruginosa, predicts a cysteine lined, GTP-gated pore

PubMed Central

Seyedmohammad, Saeed; Fuentealba, Natalia Alveal; Marriott, Robert A.J.; Goetze, Tom A.; Edwardson, J. Michael; Barrera, Nelson P.; Venter, Henrietta

2016-01-01

Iron is essential for the survival and virulence of pathogenic bacteria. The FeoB transporter allows the bacterial cell to acquire ferrous iron from its environment, making it an excellent drug target in intractable pathogens. The protein consists of an N-terminal GTP-binding domain and a C-terminal membrane domain. Despite the availability of X-ray crystal structures of the N-terminal domain, many aspects of the structure and function of FeoB remain unclear, such as the structure of the membrane domain, the oligomeric state of the protein, the molecular mechanism of iron transport, and how this is coupled to GTP hydrolysis at the N-terminal domain. In the present study, we describe the first homology model of FeoB. Due to the lack of sequence homology between FeoB and other transporters, the structures of four different proteins were used as templates to generate the homology model of full-length FeoB, which predicts a trimeric structure. We confirmed this trimeric structure by both blue-native-PAGE (BN-PAGE) and AFM. According to our model, the membrane domain of the trimeric protein forms a central pore lined by highly conserved cysteine residues. This pore aligns with a central pore in the N-terminal GTPase domain (G-domain) lined by aspartate residues. Biochemical analysis of FeoB from Pseudomonas aeruginosa further reveals a putative iron sensor domain that could connect GTP binding/hydrolysis to the opening of the pore. These results indicate that FeoB might not act as a transporter, but rather as a GTP-gated channel. PMID:26934982

The History of the APS Shock Compression of Condensed Matter Topical Group

NASA Astrophysics Data System (ADS)

Forbes, Jerry W.

2001-06-01

To provide broader scientific recognition and to advance the science of shock-compressed condensed matter, a group of APS members worked within the Society to make this technical field an active part of APS. Individual papers were given at APS meetings starting in the 1950’s and then later whole sessions were organized starting at the 1967 Pasadena meeting. Topical conferences began in 1979 in Pullman, WA where George Duvall and Dennis Hayes were co-chairs. Most all early topical conferences were sanctioned by the APS while those held after 1985 were official APS meetings. In 1984, after consulting with a number of people in the shock wave field, Robert Graham circulated a petition to form an APS topical group. He obtained signatures from a balanced cross-section of the community. William Havens, the executive secretary of APS, informed Robert Graham by letter on November 28, 1984 that the APS Council had officially accepted the formation of this topical group at its October 28, 1984 meeting. The first election occurred July 23, 1985 where Robert Graham was elected chairman, William Nellis vice-chairman, and Jerry Forbes secretary/treasurer. The topical group remains viable today by holding a topical conference in odd numbered years and shock wave sessions at APS general meetings in even numbered years A major benefit of being an official unit of APS is the allotment of APS fellows every year. The APS shock compression award established in 1987, has also provided broad recognition of many major scientific accomplishments in this field.

Application of Atmospheric-Pressure Microwave Line Plasma for Low Temperature Process

NASA Astrophysics Data System (ADS)

Suzuki, Haruka; Nakano, Suguru; Itoh, Hitoshi; Sekine, Makoto; Hori, Masaru; Toyoda, Hirotaka

2015-09-01

Atmospheric pressure (AP) plasmas have been given much attention because of its high cost benefit and a variety of possibilities for industrial applications. In various kinds of plasma production technique, pulsed-microwave discharge plasma using slot antenna is attractive due to its ability of high-density and stable plasma production. In this plasma source, however, size of the plasma has been limited up to a few cm in length due to standing wave inside a waveguide. To solve this, we have proposed a newly-developed AP microwave plasma source that utilizes not standing wave but travelling wave. By using this plasma source, spatially-uniform AP line plasma with 40 cm in length was realized by pure helium discharge in 60 cm slot and with nitrogen gas additive of 1%. Furthermore, gas temperature as low as 400 K was realized in this device. In this study, as an example of low temperature processes, hydrophilic treatment of PET films was performed. Processing speed increased with pulse frequency and a water contact angle of ~20° was easily obtained within 5 s with no thermal damage to the substrate. To evaluate treatment-uniformity of long line length, PET films were treated by 90 cm slot-antenna plasma and uniform treatment performance was confirmed.

Effect of External Photoevaporation on the Radial Transport of Volatiles and the Water Snowline in the Solar Nebula

NASA Astrophysics Data System (ADS)

Kalyaan, Anusha; Desch, Steven

2017-01-01

The Sun was likely born in a high mass star forming region [1]. Such a birth environment with a proximity to a nearby O or B star would photoevaporate the sun’s protoplanetary disk and cause an outward mass flow from the outer edge, as well as truncation of the disk, as seen in the Orion proplyds (although not as intensely)[2]. Photoevaporation likely explains the currently observed ~47 AU edge of the Kuiper Belt in our solar system [3], and more compellingly, the origin of certain short-lived radionuclides (such as Fe60), which cannot be successfully explained by a nebular origin [4][5]. Such a mass loss mechanism should affect the radial transport processes in the snowline region and along with temperature, has the potential to alter the location of the snowline.In this context, and in the light of recent ALMA observational results indicative of non-traditional behavior of snowlines and volatile transport in disks [6][7], this work studies what effect a photoevaporative mass loss from the outer disk may have on the volatile transport around the snowline region between ~1-10 AU in the disk. We build on the model of [8] and explore the effects of a steep photoevaporated non-uniform $\\alpha$ disk on radial transport of volatiles and small icy solids by incorporating the advection-diffusion equations as in [9] and condensation/evaporation of volatiles. We present results of these simulations, including volatile mass fluxes, ice/rock ratios, and snow line locations, in protoplanetary disks like the solar nebula.References: [1] Adams, F.C., 2010, ARAA 48,47 [2] Henney, W.J., & O’Dell, C.R., 1999, AJ, 118, 2350 [3] Trujillo,C.A. & Brown,M.E., 2001, ApJL,554,L95 [4] Hester, J.J., & Desch, S.J., 2005,ASPC, 341,107 [5] Wadhwa, M. et al. , 2007, Protostars & Planets V, 835 [5 [6] Cieza, L.A., et al., 2016, Nature,535,258 [7] Huang, J, et al. et al., 2016, ApJL, 823, L18 [8] Kalyaan, A., et al., 2015, ApJ, 815, 112 [9] Desch, S.J., et al., (in review).

Transport inhibition of digoxin using several common P-gp expressing cell lines is not necessarily reporting only on inhibitor binding to P-gp.

PubMed

Lumen, Annie Albin; Li, Libin; Li, Jiben; Ahmed, Zeba; Meng, Zhou; Owen, Albert; Ellens, Harma; Hidalgo, Ismael J; Bentz, Joe

2013-01-01

We have reported that the P-gp substrate digoxin required basolateral and apical uptake transport in excess of that allowed by digoxin passive permeability (as measured in the presence of GF120918) to achieve the observed efflux kinetics across MDCK-MDR1-NKI (The Netherlands Cancer Institute) confluent cell monolayers. That is, GF120918 inhibitable uptake transport was kinetically required. Therefore, IC50 measurements using digoxin as a probe substrate in this cell line could be due to inhibition of P-gp, of digoxin uptake transport, or both. This kinetic analysis is now extended to include three additional cell lines: MDCK-MDR1-NIH (National Institute of Health), Caco-2 and CPT-B2 (Caco-2 cells with BCRP knockdown). These cells similarly exhibit GF120918 inhibitable uptake transport of digoxin. We demonstrate that inhibition of digoxin transport across these cell lines by GF120918, cyclosporine, ketoconazole and verapamil is greater than can be explained by inhibition of P-gp alone. We examined three hypotheses for this non-P-gp inhibition. The inhibitors can: (1) bind to a basolateral digoxin uptake transporter, thereby inhibiting digoxin's cellular uptake; (2) partition into the basolateral membrane and directly reduce membrane permeability; (3) aggregate with digoxin in the donor chamber, thereby reducing the free concentration of digoxin, with concomitant reduction in digoxin uptake. Data and simulations show that hypothesis 1 was found to be uniformly acceptable. Hypothesis 2 was found to be uniformly unlikely. Hypothesis 3 was unlikely for GF120918 and cyclosporine, but further studies are needed to completely adjudicate whether hetero-dimerization contributes to the non-P-gp inhibition for ketoconazole and verapamil. We also find that P-gp substrates with relatively low passive permeability such as digoxin, loperamide and vinblastine kinetically require basolateral uptake transport over that allowed by +GF120918 passive permeability, while highly permeable

Transport Inhibition of Digoxin Using Several Common P-gp Expressing Cell Lines Is Not Necessarily Reporting Only on Inhibitor Binding to P-gp

PubMed Central

Lumen, Annie Albin; Li, Libin; Li, Jiben; Ahmed, Zeba; Meng, Zhou; Owen, Albert; Ellens, Harma; Hidalgo, Ismael J.; Bentz, Joe

2013-01-01

We have reported that the P-gp substrate digoxin required basolateral and apical uptake transport in excess of that allowed by digoxin passive permeability (as measured in the presence of GF120918) to achieve the observed efflux kinetics across MDCK-MDR1-NKI (The Netherlands Cancer Institute) confluent cell monolayers. That is, GF120918 inhibitable uptake transport was kinetically required. Therefore, IC50 measurements using digoxin as a probe substrate in this cell line could be due to inhibition of P-gp, of digoxin uptake transport, or both. This kinetic analysis is now extended to include three additional cell lines: MDCK-MDR1-NIH (National Institute of Health), Caco-2 and CPT-B2 (Caco-2 cells with BCRP knockdown). These cells similarly exhibit GF120918 inhibitable uptake transport of digoxin. We demonstrate that inhibition of digoxin transport across these cell lines by GF120918, cyclosporine, ketoconazole and verapamil is greater than can be explained by inhibition of P-gp alone. We examined three hypotheses for this non-P-gp inhibition. The inhibitors can: (1) bind to a basolateral digoxin uptake transporter, thereby inhibiting digoxin's cellular uptake; (2) partition into the basolateral membrane and directly reduce membrane permeability; (3) aggregate with digoxin in the donor chamber, thereby reducing the free concentration of digoxin, with concomitant reduction in digoxin uptake. Data and simulations show that hypothesis 1 was found to be uniformly acceptable. Hypothesis 2 was found to be uniformly unlikely. Hypothesis 3 was unlikely for GF120918 and cyclosporine, but further studies are needed to completely adjudicate whether hetero-dimerization contributes to the non-P-gp inhibition for ketoconazole and verapamil. We also find that P-gp substrates with relatively low passive permeability such as digoxin, loperamide and vinblastine kinetically require basolateral uptake transport over that allowed by +GF120918 passive permeability, while highly permeable

Adaptor Protein Complex 2 (AP-2) Mediated, Clathrin Dependent Endocytosis, And Related Gene Activities, Are A Prominent Feature During Maturation Stage Amelogenesis

PubMed Central

LACRUZ, Rodrigo S.; BROOKES, Steven J.; WEN, Xin; JIMENEZ, Jaime M.; VIKMAN, Susanna; HU, Ping; WHITE, Shane N.; LYNGSTADAAS, S. Petter; OKAMOTO, Curtis T.; SMITH, Charles E.; PAINE, Michael L.

2012-01-01

Molecular events defining enamel matrix removal during amelogenesis are poorly understood. Early reports have suggested that adaptor proteins (AP) participate in ameloblast-mediated endocytosis. Enamel formation involves the secretory and maturation stages, with an increase in resorptive function during the latter. Here, using real time PCR, we show that the expression of clathrin and adaptor protein subunits are up-regulated in maturation stage rodent enamel organ cells. AP-2 is the most up-regulated of the four distinct adaptor protein complexes. Immunolocalization confirms the presence of AP-2 and clathrin in ameloblasts with strongest reactivity at the apical pole. These data suggest that the resorptive functions of enamel cells involve AP-2 mediated, clathrin dependent endocytosis, thus implying the likelihood of a specific membrane-bound receptor(s) of enamel matrix protein debris. The mRNA expression of other endocytosis-related gene products is also up-regulated during maturation including: lysosomal-associated membrane protein 1 (Lamp1), cluster of differentiation 63 and 68 (Cd63 and Cd68), ATPase, H+ transporting, lysosomal V0 subunit D2 (Atp6v0d2), ATPase, H+ transporting, lysosomal V1 subunit B2 (Atp6v1b2), chloride channel, voltage-sensitive 7 (Clcn7) and cathepsin K (Ctsk). Immunohistological data confirms the expression of a number of these proteins in maturation stage ameloblasts. The enamel of Cd63-null mice was also examined. Despite increased mRNA and protein expression in the enamel organ during maturation, the enamel of Cd63-null mice appeared normal. This may suggest inherent functional redundancies between Cd63 and related gene products, such as Lamp1 and Cd68. Ameloblast-like LS8 cells treated with the enamel matrix protein complex Emdogain® showed up-regulation of AP-2 and clathrin subunits, further supporting the existence of a membrane-bound receptor regulated pathway for the endocytosis of enamel matrix proteins. These data together

AP2 hemicomplexes contribute independently to synaptic vesicle endocytosis

PubMed Central

Gu, Mingyu; Liu, Qiang; Watanabe, Shigeki; Sun, Lin; Hollopeter, Gunther; Grant, Barth D; Jorgensen, Erik M

2013-01-01

The clathrin adaptor complex AP2 is thought to be an obligate heterotetramer. We identify null mutations in the α subunit of AP2 in the nematode Caenorhabditis elegans. α-adaptin mutants are viable and the remaining μ2/β hemicomplex retains some function. Conversely, in μ2 mutants, the alpha/sigma2 hemicomplex is localized and is partially functional. α-μ2 double mutants disrupt both halves of the complex and are lethal. The lethality can be rescued by expression of AP2 components in the skin, which allowed us to evaluate the requirement for AP2 subunits at synapses. Mutations in either α or μ2 subunits alone reduce the number of synaptic vesicles by about 30%; however, simultaneous loss of both α and μ2 subunits leads to a 70% reduction in synaptic vesicles and the presence of large vacuoles. These data suggest that AP2 may function as two partially independent hemicomplexes. DOI: http://dx.doi.org/10.7554/eLife.00190.001 PMID:23482940

Tank 241-AP-105, cores 208, 209 and 210, analytical results for the final report

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

Nuzum, J.L.

1997-10-24

This document is the final laboratory report for Tank 241-AP-105. Push mode core segments were removed from Risers 24 and 28 between July 2, 1997, and July 14, 1997. Segments were received and extruded at 222-S Laboratory. Analyses were performed in accordance with Tank 241-AP-105 Push Mode Core Sampling and Analysis Plan (TSAP) (Hu, 1997) and Tank Safety Screening Data Quality Objective (DQO) (Dukelow, et al., 1995). None of the subsamples submitted for total alpha activity (AT), differential scanning calorimetry (DSC) analysis, or total organic carbon (TOC) analysis exceeded the notification limits as stated in TSAP and DQO. The statisticalmore » results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems Technical Basis Group, and are not considered in this report. Appearance and Sample Handling Two cores, each consisting of four segments, were expected from Tank 241-AP-105. Three cores were sampled, and complete cores were not obtained. TSAP states core samples should be transported to the laboratory within three calendar days from the time each segment is removed from the tank. This requirement was not met for all cores. Attachment 1 illustrates subsamples generated in the laboratory for analysis and identifies their sources. This reference also relates tank farm identification numbers to their corresponding 222-S Laboratory sample numbers.« less

Enigma interacts with adaptor protein with PH and SH2 domains to control insulin-induced actin cytoskeleton remodeling and glucose transporter 4 translocation.

PubMed

Barrès, Romain; Grémeaux, Thierry; Gual, Philippe; Gonzalez, Teresa; Gugenheim, Jean; Tran, Albert; Le Marchand-Brustel, Yannick; Tanti, Jean-François

2006-11-01

APS (adaptor protein with PH and SH2 domains) initiates a phosphatidylinositol 3-kinase-independent pathway involved in insulin-stimulated glucose transport. We recently identified Enigma, a PDZ and LIM domain-containing protein, as a partner of APS and showed that APS-Enigma complex plays a critical role in actin cytoskeleton organization in fibroblastic cells. Because actin rearrangement is important for insulin-induced glucose transporter 4 (Glut 4) translocation, we studied the potential involvement of Enigma in insulin-induced glucose transport in 3T3-L1 adipocytes. Enigma mRNA was expressed in differentiated adipocytes and APS and Enigma were colocalized with cortical actin. Expression of an APS mutant unable to bind Enigma increased the insulin-induced Glut 4 translocation to the plasma membrane. By contrast, overexpression of Enigma inhibited insulin-stimulated glucose transport and Glut 4 translocation without alterations in proximal insulin signaling. This inhibitory effect was prevented with the deletion of the LIM domains of Enigma. Using time-lapse fluorescent microscopy of green fluorescent protein-actin, we demonstrated that the overexpression of Enigma altered insulin-induced actin rearrangements, whereas the expression of Enigma without its LIM domains was without effect. A physiological link between increased expression of Enigma and an alteration in insulin-induced glucose uptake was suggested by the increase in Enigma mRNA expression in adipose tissue of diabetic obese patients. Taken together, these data strongly suggest that the interaction between APS and Enigma is involved in insulin-induced Glut 4 translocation by regulating cortical actin remodeling and raise the possibility that modification of APS/Enigma ratio could participate in the alteration of insulin-induced glucose uptake in adipose tissue.

Teaching Materials and Strategies for the AP Music Theory Exam

ERIC Educational Resources Information Center

Lively, Michael T.

2017-01-01

Each year, many students take the Advanced Placement (AP) Music Theory Exam, and the majority of these students enroll in specialized AP music theory classes as part of the preparation process. For the teachers of these AP music theory classes, a number of challenges are presented by the difficulty and complexity of the exam subject material as…

NECAPs are negative regulators of the AP2 clathrin adaptor complex.

PubMed

Beacham, Gwendolyn M; Partlow, Edward A; Lange, Jeffrey J; Hollopeter, Gunther

2018-01-18

Eukaryotic cells internalize transmembrane receptors via clathrin-mediated endocytosis, but it remains unclear how the machinery underpinning this process is regulated. We recently discovered that membrane-associated muniscin proteins such as FCHo and SGIP initiate endocytosis by converting the AP2 clathrin adaptor complex to an open, active conformation that is then phosphorylated (Hollopeter et al., 2014). Here we report that loss of ncap-1 , the sole C. elegans gene encoding an adaptiN Ear-binding Coat-Associated Protein (NECAP), bypasses the requirement for FCHO-1. Biochemical analyses reveal AP2 accumulates in an open, phosphorylated state in ncap-1 mutant worms, suggesting NECAPs promote the closed, inactive conformation of AP2. Consistent with this model, NECAPs preferentially bind open and phosphorylated forms of AP2 in vitro and localize with constitutively open AP2 mutants in vivo. NECAPs do not associate with phosphorylation-defective AP2 mutants, implying that phosphorylation precedes NECAP recruitment. We propose NECAPs function late in endocytosis to inactivate AP2. © 2018, Beacham et al.

AP-1-mediated chromatin looping regulates ZEB2 transcription: new insights into TNFα-induced epithelial-mesenchymal transition in triple-negative breast cancer.

PubMed

Qiao, Yichun; Shiue, Chiou-Nan; Zhu, Jian; Zhuang, Ting; Jonsson, Philip; Wright, Anthony P H; Zhao, Chunyan; Dahlman-Wright, Karin

2015-04-10

The molecular determinants of malignant cell behaviour in triple-negative breast cancer (TNBC) are poorly understood. Recent studies have shown that regulators of epithelial-mesenchymal transition (EMT) are potential therapeutic targets for TNBC. In this study, we demonstrate that the inflammatory cytokine TNFα induces EMT in TNBC cells via activation of AP-1 signaling and subsequently induces expression of the EMT regulator ZEB2. We also show that TNFα activates both the PI3K/Akt and MAPK/ERK pathways, which act upstream of AP-1. We further investigated in detail AP-1 regulation of ZEB2 expression. We show that two ZEB2 transcripts derived from distinct promoters are both expressed in breast cancer cell lines and breast tumor samples. Using the chromosome conformation capture assay, we demonstrate that AP-1, when activated by TNFα, binds to a site in promoter 1b of the ZEB2 gene where it regulates the expression of both promoter 1b and 1a, the latter via mediating long range chromatin interactions. Overall, this work provides a plausible mechanism for inflammation-induced metastatic potential in TNBC, involving a novel regulatory mechanism governing ZEB2 isoform expression.

AP-1-mediated chromatin looping regulates ZEB2 transcription: new insights into TNFα-induced epithelial–mesenchymal transition in triple-negative breast cancer

PubMed Central

Qiao, Yichun; Shiue, Chiou-Nan; Zhu, Jian; Zhuang, Ting; Jonsson, Philip; Wright, Anthony P.H.; Zhao, Chunyan; Dahlman-Wright, Karin

2015-01-01

The molecular determinants of malignant cell behaviour in triple-negative breast cancer (TNBC) are poorly understood. Recent studies have shown that regulators of epithelial-mesenchymal transition (EMT) are potential therapeutic targets for TNBC. In this study, we demonstrate that the inflammatory cytokine TNFα induces EMT in TNBC cells via activation of AP-1 signaling and subsequently induces expression of the EMT regulator ZEB2. We also show that TNFα activates both the PI3K/Akt and MAPK/ERK pathways, which act upstream of AP-1. We further investigated in detail AP-1 regulation of ZEB2 expression. We show that two ZEB2 transcripts derived from distinct promoters are both expressed in breast cancer cell lines and breast tumor samples. Using the chromosome conformation capture assay, we demonstrate that AP-1, when activated by TNFα, binds to a site in promoter 1b of the ZEB2 gene where it regulates the expression of both promoter 1b and 1a, the latter via mediating long range chromatin interactions. Overall, this work provides a plausible mechanism for inflammation-induced metastatic potential in TNBC, involving a novel regulatory mechanism governing ZEB2 isoform expression. PMID:25762639

Is the Shine off the A.P. Apple?

ERIC Educational Resources Information Center

Hurwitz, Nina; Hurwitz, Sol

2003-01-01

Describes challenges facing College Board's efforts to expand Advanced Placement (A.P.) courses to provide equal access to previously underserved low-performing urban and rural school students while maintaining the program's high academic standards. Includes list of strategies school boards can use to achieve greater access to A.P. courses while…

AP233: An Information Model for Systems Engineering

NASA Technical Reports Server (NTRS)

Siebes, Georg

2009-01-01

In today's world, information is abundant. We have no problems generating it. But we are challenged to find, organize, and exchange information. center dot A standardized model of information can help. Such a model nearly completed its development for Systems Engineering. It is referred to as AP233 (AP = Application Protocol).

The Role of AP and the Composition Program.

ERIC Educational Resources Information Center

Mahala, Daniel; Vivion, Michael

1993-01-01

Suggests that most programs have not based their acceptance of advanced placement credit on reasoned endorsement of the views of language, literature, and rhetoric that AP exams present. Criticizes the views implicit in the AP program and shows how they conflict with the goals of one particular college composition program. (RS)

Transport of liquid state nitrogen through long length service lines during thermal/vacuum testing. [in a Nimbus 6 satellite

NASA Technical Reports Server (NTRS)

Florio, F. A.

1975-01-01

Physical and analytical aspects associated with the transport are presented. Included is a definition of the problems and difficulties imposed by the servicing of a typical solid cryogen system, as well as a discussion of the transport requirements and of the rationale which governed their solution. A successful detailed transport configuration is defined, and the application of established mathematics to the design approach is demonstrated. The significance of head pressure, pressure drop, line friction, heat leak, Reynolds number, and the fundamental equilibrium demands of pressure and temperature were examined as they relate to the achievement of liquid state flow. Performance predictions were made for the transport system, and several analytical quantities are tabulated. These data are analyzed and compared with measured and calculated results obtained while actually servicing a solid cryogen system during thermal/vacuum testing.

Prevention of Breast Cell Transformation by Blockade of the AP-1 Transcription Factor

DTIC Science & Technology

2000-10-01

Distribution Unlimited 13. ABSTRACT (Maximum 200 Words) In this study, we are investigating the role of AP- M in controlling breast cell growth and...serum and these growth factors depend on AP-1 to transduce proliferative signal. AP- M blockade induced by the expression of TAM67 inhibits breast...demonstrated that TAM67 inhibits basal AP-1 activity and AP- M activity stimulated by several different growth factors. We have also discovered that AP-1

49 CFR 192.706 - Transmission lines: Leakage surveys.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Transmission lines: Leakage surveys. 192.706... Transmission lines: Leakage surveys. Leakage surveys of a transmission line must be conducted at intervals not... transports gas in conformity with § 192.625 without an odor or odorant, leakage surveys using leak detector...

49 CFR 192.706 - Transmission lines: Leakage surveys.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Transmission lines: Leakage surveys. 192.706... Transmission lines: Leakage surveys. Leakage surveys of a transmission line must be conducted at intervals not... transports gas in conformity with § 192.625 without an odor or odorant, leakage surveys using leak detector...

49 CFR 192.706 - Transmission lines: Leakage surveys.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Transmission lines: Leakage surveys. 192.706... Transmission lines: Leakage surveys. Leakage surveys of a transmission line must be conducted at intervals not... transports gas in conformity with § 192.625 without an odor or odorant, leakage surveys using leak detector...

49 CFR 192.706 - Transmission lines: Leakage surveys.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Transmission lines: Leakage surveys. 192.706... Transmission lines: Leakage surveys. Leakage surveys of a transmission line must be conducted at intervals not... transports gas in conformity with § 192.625 without an odor or odorant, leakage surveys using leak detector...

49 CFR 192.706 - Transmission lines: Leakage surveys.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Transmission lines: Leakage surveys. 192.706... Transmission lines: Leakage surveys. Leakage surveys of a transmission line must be conducted at intervals not... transports gas in conformity with § 192.625 without an odor or odorant, leakage surveys using leak detector...

Esterification of Quercetin Increases Its Transport Across Human Caco-2 Cells.

PubMed

Hu, Jiang-Ning; Zou, Xian-Guo; He, Yi; Chen, Fang; Deng, Ze-Yuan

2016-07-01

Plant polyphenols showed useful biochemical characteristics in vitro; however, the assessments of their clinical applications in vivo are restricted by their limited bioavailability due to their strong resistance to 1st-pass effects during absorption. In order to improve the bioavailability of quercetin (QU), the ester derivative of QU (3,3',4',5,7-pentahydroxy flavones, TAQU) was synthesized, followed by examining the oil-water partition coefficient as well as the transport mechanisms of QU and its ester derivative (TAQU) using human Caco-2 cells. The transport characteristics of QU and TAQU transport under different conditions (different concentrations, time, pH, temperature, tight junctions, and potential transporters) were systematically investigated. Results showed that QU had a lower permeability coefficient (2.82 × 10(-6) cm/s) for apical-to-basolateral (AP-BL) transport over 5 to 50 μM, whereas the transport rate for AP to BL flux of TAQU (5.23 × 10(-6) cm/s) was significantly greater than that of QU. Paracellular pathways were not involved during the transport of both QU and TAQU. QU was poorly absorbed by active transport, whereas TAQU was mostly absorbed by passive diffusion. Efflux transporters, P-glycoproteins, multidrug resistance proteins were proven to participate in the transport process of QU, but not in that of TAQU. These results suggested that improving the lipophicity of QU by esterification could increase the transport of QU across Caco-2 cells. © 2016 Institute of Food Technologists®

Computer simulations of transport through membranes: passive diffusion, pores, channels and transporters.

PubMed

Tieleman, D Peter

2006-10-01

A key function of biological membranes is to provide mechanisms for the controlled transport of ions, nutrients, metabolites, peptides and proteins between a cell and its environment. We are using computer simulations to study several processes involved in transport. In model membranes, the distribution of small molecules can be accurately calculated; we are making progress towards understanding the factors that determine the partitioning behaviour in the inhomogeneous lipid environment, with implications for drug distribution, membrane protein folding and the energetics of voltage gating. Lipid bilayers can be simulated at a scale that is sufficiently large to study significant defects, such as those caused by electroporation. Computer simulations of complex membrane proteins, such as potassium channels and ATP-binding cassette (ABC) transporters, can give detailed information about the atomistic dynamics that form the basis of ion transport, selectivity, conformational change and the molecular mechanism of ATP-driven transport. This is illustrated in the present review with recent simulation studies of the voltage-gated potassium channel KvAP and the ABC transporter BtuCD.

AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance

PubMed Central

O’Hare, Thomas; Shakespeare, William C.; Zhu, Xiaotian; Eide, Christopher A.; Rivera, Victor M.; Wang, Frank; Adrian, Lauren T.; Zhou, Tianjun; Huang, Wei-Sheng; Xu, Qihong; Metcalf, Chester A.; Tyner, Jeffrey W.; Loriaux, Marc M.; Corbin, Amie S.; Wardwell, Scott; Ning, Yaoyu; Keats, Jeffrey A.; Wang, Yihan; Sundaramoorthi, Raji; Thomas, Mathew; Zhou, Dong; Snodgrass, Joseph; Commodore, Lois; Sawyer, Tomi K.; Dalgarno, David C.; Deininger, Michael W.N.; Druker, Brian J.; Clackson, Tim

2009-01-01

SUMMARY Inhibition of BCR-ABL by imatinib induces durable responses in many patients with chronic myeloid leukemia (CML), but resistance attributable to kinase domain mutations can lead to relapse and a switch to second-line therapy with nilotinib or dasatinib. Despite three approved therapeutic options, the cross-resistant BCR-ABLT315I mutation and compound mutants selected on sequential inhibitor therapy remain major clinical challenges. We report design and pre-clinical evaluation of AP24534, a potent, orally available multi-targeted kinase inhibitor active against T315I and other BCR-ABL mutants. AP24534 inhibited all tested BCR-ABL mutants in cellular and biochemical assays, suppressed BCR-ABLT315I-driven tumor growth in mice, and completely abrogated resistance in cell-based mutagenesis screens. Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML. PMID:19878872

AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance

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

O’Hare, Thomas; Shakespeare, William C.; Zhu, Xiaotian

2010-09-07

Inhibition of BCR-ABL by imatinib induces durable responses in many patients with chronic myeloid leukemia (CML), but resistance attributable to kinase domain mutations can lead to relapse and a switch to second-line therapy with nilotinib or dasatinib. Despite three approved therapeutic options, the cross-resistant BCR-ABL{sup T315I} mutation and compound mutants selected on sequential inhibitor therapy remain major clinical challenges. We report design and preclinical evaluation of AP24534, a potent, orally available multitargeted kinase inhibitor active against T315I and other BCR-ABL mutants. AP24534 inhibited all tested BCR-ABL mutants in cellular and biochemical assays, suppressed BCR-ABL{sup T315I}-driven tumor growth in mice, andmore » completely abrogated resistance in cell-based mutagenesis screens. Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML.« less

AP@home: a novel European approach to bring the artificial pancreas home.

PubMed

Heinemann, Lutz; Benesch, Carsten; DeVries, J Hans

2011-11-01

The development of an artificial pancreas (AP) made huge strides from 2006 to 2008 and a large number of activities are going on in this area of research. Until now, most AP systems under development were tested only under highly controlled conditions. The aim of our project, funded by the European Union, is to develop an AP system to such a level that it can be studied under daily life conditions at the home of patients with diabetes (hence AP@home). Based on a subcutaneous-subcutaneous closed-loop strategy (i.e., glucose sensing and insulin infusion in the subcutaneous tissue), two different approaches will be taken to achieve this aim: a two-port AP system and a single-port AP system. The two-port AP system will use off-the-shelf-components for the glucose sensor and insulin pump in combination with closed-loop algorithms generated in Europe. As to the single-port AP system, two different innovative single-port systems will be developed; in this case, continuous glucose monitoring and insulin infusion will take place via a single catheter. The first clinical trials with the two-port AP system under controlled clinical conditions have started and good progress has been made in the development of the single-port AP systems. We believe that our consortium of 12 European partners, which builds on existing achievements and close cooperation between academic centers and industry, can contribute substantially to the development of an AP system that can be used by patients in daily life. © 2011 Diabetes Technology Society.

Glossary for the implementation of Health in All Policies (HiAP).

PubMed

Freiler, Alix; Muntaner, Carles; Shankardass, Ketan; Mah, Catherine L; Molnar, Agnes; Renahy, Emilie; O'Campo, Patricia

2013-12-01

Health in All Policies (HiAP) is becoming increasingly popular as a governmental strategy to improve population health by coordinating action across health and non-health sectors. A variety of intersectoral initiatives may be used in HiAP that frame health determinants as the bridge between policies and health outcomes. The purpose of this glossary is to present concepts and terms useful in understanding the implementation of HiAP as a cross-sectoral policy. The concepts presented here were applied and elaborated over the course of case studies of HiAP in multiple jurisdictions, which used key informant interviews and the systematic review of literature to study the implementation of specific HiAP initiatives.

CaAP2 transcription factor is a candidate gene for a flowering repressor and a candidate for controlling natural variation of flowering time in Capsicum annuum.

PubMed

Borovsky, Yelena; Sharma, Vinod K; Verbakel, Henk; Paran, Ilan

2015-06-01

The APETALA2 transcription factor homolog CaAP2 is a candidate gene for a flowering repressor in pepper, as revealed by induced-mutation phenotype, and a candidate underlying a major QTL controlling natural variation in flowering time. To decipher the genetic control of transition to flowering in pepper (Capsicum spp.) and determine the extent of gene function conservation compared to model species, we isolated and characterized several ethyl methanesulfonate (EMS)-induced mutants that vary in their flowering time compared to the wild type. In the present study, we report on the isolation of an early-flowering mutant that flowers after four leaves on the primary stem compared to nine leaves in the wild-type 'Maor'. By genetic mapping and sequencing of putative candidate genes linked to the mutant phenotype, we identified a member of the APETALA2 (AP2) transcription factor family, CaAP2, which was disrupted in the early-flowering mutant. CaAP2 is a likely ortholog of AP2 that functions as a repressor of flowering in Arabidopsis. To test whether CaAP2 has an effect on controlling natural variation in the transition to flowering in pepper, we performed QTL mapping for flowering time in a cross between early and late-flowering C. annuum accessions. We identified a major QTL in a region of chromosome 2 in which CaAP2 was the most significant marker, explaining 52 % of the phenotypic variation of the trait. Sequence comparison of the CaAP2 open reading frames in the two parents used for QTL mapping did not reveal significant variation. In contrast, significant differences in expression level of CaAP2 were detected between near-isogenic lines that differ for the flowering time QTL, supporting the putative function of CaAP2 as a major repressor of flowering in pepper.

Clathrin and AP1 are required for apical sorting of glycosyl phosphatidyl inositol-anchored proteins in biosynthetic and recycling routes in Madin-Darby canine kidney cells.

PubMed

Castillon, Guillaume A; Burriat-Couleru, Patricia; Abegg, Daniel; Criado Santos, Nina; Watanabe, Reika

2018-03-01

Recently, studies in animal models demonstrate potential roles for clathrin and AP1 in apical protein sorting in epithelial tissue. However, the precise functions of these proteins in apical protein transport remain unclear. Here, we reveal mistargeting of endogenous glycosyl phosphatidyl inositol-anchored proteins (GPI-APs) and soluble secretory proteins in Madin-Darby canine kidney (MDCK) cells upon clathrin heavy chain or AP1 subunit knockdown (KD). Using a novel directional endocytosis and recycling assay, we found that these KD cells are not only affected for apical sorting of GPI-APs in biosynthetic pathway but also for their apical recycling and basal-to-apical transcytosis routes. The apical distribution of the t-SNARE syntaxin 3, which is known to be responsible for selective targeting of various apical-destined cargo proteins in both biosynthetic and endocytic routes, is compromised suggesting a molecular explanation for the phenotype in KD cells. Our results demonstrate the importance of biosynthetic and endocytic routes for establishment and maintenance of apical localization of GPI-APs in polarized MDCK cells. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The APS SASE FEL : modeling and code comparison.

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

Biedron, S. G.

A self-amplified spontaneous emission (SASE) free-electron laser (FEL) is under construction at the Advanced Photon Source (APS). Five FEL simulation codes were used in the design phase: GENESIS, GINGER, MEDUSA, RON, and TDA3D. Initial comparisons between each of these independent formulations show good agreement for the parameters of the APS SASE FEL.

EPA’s AP-42 development methodology: Converting or rerating current AP-42 datasets

USDA-ARS?s Scientific Manuscript database

In August 2013, the U.S. Environmental Protection Agency’s (EPA) published their new methodology for updating the Compilation of Air Pollution Emission Factors (AP-42). The “Recommended Procedures for Development of Emissions Factors and Use of the WebFIRE Database” instructs that the ratings of the...

AP1000{sup R} licensing and deployment in the United States

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

Jordan, R. P.; Russ, P. A.; Filiak, P. P.

2012-07-01

In recent years, both domestic and foreign utilities have turned to the standardized Westinghouse AP1000 plant design in satisfying their near - and long-term - sustainable energy needs. As direct support to these actions, licensing the AP1000 design has played a significant role by providing one of the fundamental bases in clearing regulatory hurdles leading to the start of new plant construction. Within the U.S. alone, Westinghouse AP1000 licensing activities have reached unprecedented milestones with the approvals of both AP1000 Design Certification and Southern Company's combined construction permit and operating license (COL) application directly supporting the construction of two newmore » nuclear plants in Georgia. Further COL application approvals are immediately pending for an additional two AP1000 plants in South Carolina. And, across the U.S. nuclear industry spectrum, there are 10 other COL applications under regulatory review representing some 16 new plants at 10 sites. In total, these actions represent the first wave of new plant licensing under the regulatory approval process since 1978. Fundamental to the Nuclear Regulatory Commission's AP1000 Design Certification is the formal recognition of the AP1000 passive safety design through regulatory acceptance rulemaking. Through recognition and deployment of the AP1000 Design Certification, the utility licensee / operator of this reactor design are now offered an opportunity to use a simplified 'one-step' combined license process, thereby managing substantial back-end construction schedule risk from regulatory and intervention delays. Application of this regulatory philosophy represents both acceptance and encouragement of standardized reactor designs like the AP1000. With the recent AP1000 Design Certification and utility COL acceptances, the fundamental licensing processes of this philosophy have successfully proven the attainment of significant milestones with the next stage licensing actions

A seven-year northern sky survey of Ap stars for rapid variability

NASA Technical Reports Server (NTRS)

Nelson, Matthew J.; Kreidl, Tobias J.

1993-01-01

A high-speed photometric survey of 120 Ap stars in the northern sky, has been conducted, between 1985 and 1991, in order to search for rapid variability. Stars of spectral types, namely from B8 to F4, have been selected for the survey. The selected pulsational variable stars occupy the hotter regions of the instability strip of the Hertzsprung-Russel diagram. Noted is the absence of pulsations in the hotter B8-A3 Ap stars; this does not, however, preclude the existence of pulsations, since HD 218495 was recently discovered to be a rapidly oscillating Ap (roAp) star. The primary result of this study is that various combinations of photometric indices, while pointing towards roAp stars having the characteristic signatures of cool, SrCrEu stars, still fail to isolate the roAp phenomenon from similar nonpulsating Ap stars. Color-magnitude and color-color diagrams are presented in order to complete this survey.

SEPTUM MAGNET DESIGN FOR THE APS-U

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

Abliz, M.; Jaski, M.; Xiao, A.

2017-06-25

The Advanced Photon Source is in the process of upgrading its storage ring from a double-bend to a multi-bend lattice as part of the APS Upgrade Project (APS-U). A swap-out injection scheme is planned for the APS-U to keep a constant beam current and to enable a small dynamic aperture. A septum magnet with a minimum thickness of 2 mm and an injection field of 1.06 T has been designed, delivering the required total deflecting angle is 89 mrad with a ring energy of 6 GeV. The stored beam chamber has an 8 mm x 6 mm super-ellipsoidal aperture. Themore » magnet is straight; however, it is tilted in yaw, roll, and pitch from the stored beam chamber to meet the on axis swap out injection requirements for the APS-U lattice. In order to minimize the leakage field inside the stored beam chamber, four different techniques were utilized in the design. As a result, the horizontal deflecting angle of the stored beam was held to only 5 µrad, and the integrated skew quadrupole inside the stored beam chamber was held to 0.09 T. The detailed techniques that were applied to the design, field multipoles, and resulting trajectories of the injected and stored beams are reported.« less

Radioactive air emissions notice of construction for installation and operation of a waste retrieval system and tanks 241-AP-102 and 241-AP-104 project

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

DEXTER, M.L.

1999-11-15

This document serves as a notice of construction (NOC) pursuant to the requirements of Washington Administrative Code (WAC) 246 247-060, and as a request for approval to modify pursuant to 40 Code of Federal Regulations (CFR) 61 07 for the installation and operation of one waste retrieval system in the 24 1 AP-102 Tank and one waste retrieval system in the 241 AP 104 Tank Pursuant to 40 CFR 61 09 (a)( 1) this application is also intended to provide anticipated initial start up notification Its is requested that EPA approval of this application will also constitute EPA acceptance ofmore » the initial start up notification Project W 211 Initial Tank Retrieval Systems (ITRS) is scoped to install a waste retrieval system in the following double-shell tanks 241-AP 102-AP 104 AN 102, AN 103, AN-104, AN 105, AY 102 AZ 102 and SY-102 between now and the year 2011. Because of the extended installation schedules and unknowns about specific activities/designs at each tank, it was decided to submit NOCs as that information became available This NOC covers the installation and operation of a waste retrieval system in tanks 241 AP-102 and 241 AP 104 Generally this includes removal of existing equipment installation of new equipment and construction of new ancillary equipment and buildings Tanks 241 AP 102 and 241 AP 104 will provide waste feed for immobilization into a low activity waste (LAW) product (i.e. glass logs) The total effective dose equivalent (TEDE) to the offsite maximally exposed individual (MEI) from the construction activities is 0 045 millirem per year The unabated TEDE to the offsite ME1 from operation of the mixer pumps is 0 042 millirem per year.« less

AP-2α and AP-2β cooperatively orchestrate homeobox gene expression during branchial arch patterning.

PubMed

Van Otterloo, Eric; Li, Hong; Jones, Kenneth L; Williams, Trevor

2018-01-25

The evolution of a hinged moveable jaw with variable morphology is considered a major factor behind the successful expansion of the vertebrates. DLX homeobox transcription factors are crucial for establishing the positional code that patterns the mandible, maxilla and intervening hinge domain, but how the genes encoding these proteins are regulated remains unclear. Herein, we demonstrate that the concerted action of the AP-2α and AP-2β transcription factors within the mouse neural crest is essential for jaw patterning. In the absence of these two proteins, the hinge domain is lost and there are alterations in the size and patterning of the jaws correlating with dysregulation of homeobox gene expression, with reduced levels of Emx, Msx and Dlx paralogs accompanied by an expansion of Six1 expression. Moreover, detailed analysis of morphological features and gene expression changes indicate significant overlap with various compound Dlx gene mutants. Together, these findings reveal that the AP-2 genes have a major function in mammalian neural crest development, influencing patterning of the craniofacial skeleton via the DLX code, an effect that has implications for vertebrate facial evolution, as well as for human craniofacial disorders. © 2018. Published by The Company of Biologists Ltd.

Radial transport of radiation belt electrons in kinetic field-line resonances

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

Chaston, Christopher C.; Bonnell, J. W.; Wygant, J. R.

A representative case study from the Van Allen Probes during a geomagnetic storm recovery phase reveals enhanced electron fluxes at intermediate pitch angles over energies from ~100 keV to 5 MeV coincident with broadband low-frequency electromagnetic waves. The statistical properties of these waves are used to build a model for radial diffusion via drift-bounce resonances in kinetic Alfvén eigenmodes/kinetic field-line resonances. Estimated diffusion coefficients indicate timescales for radial transport on the order of hours in storm time events at energies from <100 keV to MeVs over equatorial pitch angles from the edge of the loss cone to nearly perpendicular tomore » the geomagnetic field. In conclusion, the correlation of kinetic resonances with electron depletions and enhancements during storm main phase and recovery, and the rapid diffusion these waves drive, suggests that they may modulate the outer radiation belt.« less

Radial transport of radiation belt electrons in kinetic field-line resonances

DOE PAGES

Chaston, Christopher C.; Bonnell, J. W.; Wygant, J. R.; ...

2017-07-25

A representative case study from the Van Allen Probes during a geomagnetic storm recovery phase reveals enhanced electron fluxes at intermediate pitch angles over energies from ~100 keV to 5 MeV coincident with broadband low-frequency electromagnetic waves. The statistical properties of these waves are used to build a model for radial diffusion via drift-bounce resonances in kinetic Alfvén eigenmodes/kinetic field-line resonances. Estimated diffusion coefficients indicate timescales for radial transport on the order of hours in storm time events at energies from <100 keV to MeVs over equatorial pitch angles from the edge of the loss cone to nearly perpendicular tomore » the geomagnetic field. In conclusion, the correlation of kinetic resonances with electron depletions and enhancements during storm main phase and recovery, and the rapid diffusion these waves drive, suggests that they may modulate the outer radiation belt.« less

49 CFR 393.90 - Buses, standee line or bar.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Buses, standee line or bar. 393.90 Section 393.90 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY... NECESSARY FOR SAFE OPERATION Miscellaneous Parts and Accessories § 393.90 Buses, standee line or bar. Except...

Comparison of a Rat Primary Cell-Based Blood-Brain Barrier Model With Epithelial and Brain Endothelial Cell Lines: Gene Expression and Drug Transport.

PubMed

Veszelka, Szilvia; Tóth, András; Walter, Fruzsina R; Tóth, Andrea E; Gróf, Ilona; Mészáros, Mária; Bocsik, Alexandra; Hellinger, Éva; Vastag, Monika; Rákhely, Gábor; Deli, Mária A

2018-01-01

Cell culture-based blood-brain barrier (BBB) models are useful tools for screening of CNS drug candidates. Cell sources for BBB models include primary brain endothelial cells or immortalized brain endothelial cell lines. Despite their well-known differences, epithelial cell lines are also used as surrogate models for testing neuropharmaceuticals. The aim of the present study was to compare the expression of selected BBB related genes including tight junction proteins, solute carriers (SLC), ABC transporters, metabolic enzymes and to describe the paracellular properties of nine different culture models. To establish a primary BBB model rat brain capillary endothelial cells were co-cultured with rat pericytes and astrocytes (EPA). As other BBB and surrogate models four brain endothelial cells lines, rat GP8 and RBE4 cells, and human hCMEC/D3 cells with or without lithium treatment (D3 and D3L), and four epithelial cell lines, native human intestinal Caco-2 and high P-glycoprotein expressing vinblastine-selected VB-Caco-2 cells, native MDCK and MDR1 transfected MDCK canine kidney cells were used. To test transporter functionality, the permeability of 12 molecules, glucopyranose, valproate, baclofen, gabapentin, probenecid, salicylate, rosuvastatin, pravastatin, atorvastatin, tacrine, donepezil, was also measured in the EPA and epithelial models. Among the junctional protein genes, the expression level of occludin was high in all models except the GP8 and RBE4 cells, and each model expressed a unique claudin pattern. Major BBB efflux (P-glycoprotein or ABCB1) and influx transporters (GLUT-1, LAT-1) were present in all models at mRNA levels. The transcript of BCRP (ABCG2) was not expressed in MDCK, GP8 and RBE4 cells. The absence of gene expression of important BBB efflux and influx transporters BCRP, MRP6, -9, MCT6, -8, PHT2, OATPs in one or both types of epithelial models suggests that Caco-2 or MDCK models are not suitable to test drug candidates which are substrates

LC-MS/MS Based Quantitation of ABC and SLC Transporter Proteins in Plasma Membranes of Cultured Primary Human Retinal Pigment Epithelium Cells and Immortalized ARPE19 Cell Line.

PubMed

Pelkonen, Laura; Sato, Kazuki; Reinisalo, Mika; Kidron, Heidi; Tachikawa, Masanori; Watanabe, Michitoshi; Uchida, Yasuo; Urtti, Arto; Terasaki, Tetsuya

2017-03-06

The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier between neural retina and choroid. The RPE has several important vision supporting functions, such as transport mechanisms that may also modify pharmacokinetics in the posterior eye segment. Expression of plasma membrane transporters in the RPE cells has not been quantitated. The aim of this study was to characterize and compare transporter protein expression in the ARPE19 cell line and hfRPE (human fetal RPE) cells by using quantitative targeted absolute proteomics (QTAP). Among 41 studied transporters, 16 proteins were expressed in hfRPE and 13 in ARPE19 cells. MRP1, MRP5, GLUT1, 4F2hc, TAUT, CAT1, LAT1, and MATE1 proteins were detected in both cell lines within 4-fold differences. MPR7, OAT2 and RFC1 were detected in the hfRPE cells, but their expression levels were below the limit of quantification in ARPE19 cells. PCFT was detected in both studied cell lines, but the expression was over 4-fold higher in hfRPE cells. MCT1, MCT4, MRP4, and Na + /K + ATPase were upregulated in the ARPE19 cell line showing over 4-fold differences in the quantitative expression values. Expression levels of 25 transporters were below the limit of quantification in both cell models. In conclusion, we present the first systematic and quantitative study on transporter protein expression in the plasma membranes of ARPE19 and hfRPE cells. Overall, transporter expression in the ARPE19 and hfRPE cells correlated well and the absolute expression levels were similar, but not identical. The presented quantitative expression levels could be a useful basis for further studies on drug permeation in the outer blood-retinal barrier.

Advancing beyond AP Courses

ERIC Educational Resources Information Center

Hammond, Bruce G.

2009-01-01

A quiet revolution is picking up steam in the nation's private secondary schools, with broad implications for college admissions and for teaching and learning on both sides of the transition from high school to college. About 50 of the nation's leading college-preparatory schools have opted out of the College Board's Advanced Placement (AP)…

Fun at Antarctic grounding lines: Ice-shelf channels and sediment transport

NASA Astrophysics Data System (ADS)

Drews, Reinhard; Mayer, Christoph; Eisen, Olaf; Helm, Veit; Ehlers, Todd A.; Pattyn, Frank; Berger, Sophie; Favier, Lionel; Hewitt, Ian H.; Ng, Felix; Fürst, Johannes J.; Gillet-Chaulet, Fabien; Bergeot, Nicolas; Matsuoka, Kenichi

2017-04-01

Meltwater beneath the polar ice sheets drains, in part, through subglacial conduits. Landforms created by such drainages are abundant in areas formerly covered by ice sheets during the last glacial maximum. However, observations of subglacial conduit dynamics under a contemporary ice sheet are lacking. We present results from ice-penetrating radar to infer the existence of subglacial conduits upstream of the grounding line of Roi Baudouin Ice Shelf, Antarctica. The conduits are aligned with ice-shelf channels, and underlain by esker ridges formed from sediment deposition due to reduced water outflow speed near the grounding line. In turn, the eskers modify local ice flow to initiate the bottom topography of the ice-shelf channels, and create small surface ridges extending onto the shelf. Relict features on the shelf are interpreted to indicate a history of these interactions and variability of past subglacial drainages. Because ice-shelf channels are loci where intense melting occurs to thin an ice shelf, these findings expose a novel link between subglacial drainage, sedimentation, and ice-shelf stability. To investigate the role of sediment transport beneath ice sheets further, we model the sheet-shelf system of the Ekstömisen catchment, Antarctica. A 3D finite element model (Elmer/ICE) is used to solve the transients full Stokes equation for isotropic, isothermal ice with a dynamic grounding line. We initialize the model with surface topography from the TanDEM-X satellites and by inverting simultaneously for ice viscosity and basal drag using present-day surface velocities. Results produce a flow field which is consitent with sattelite and on-site observations. Solving the age-depth relationship allows comparison with radar isochrones from airborne data, and gives information about the atmospheric/dynamic history of this sector. The flow field will eventually be used to identify potential sediment sources and sinks which we compare with more than 400 km of

An improved model for the combustion of AP composite propellants

NASA Technical Reports Server (NTRS)

Cohen, N. S.; Strand, L. D.

1981-01-01

This paper presents several improvements to the BDP model of steady-state burning of AP composite solid propellants. The Price-Boggs-Derr model of AP monopropellant burning is incorporated to represent the AP. A separate energy equation is written for the binder to permit a different surface temperature from the AP; this includes an analysis of the sharing of primary diffusion flame energy, and correction of a BDP model inconsistency in treating the binder regression rate. A method for assembling component contributions to calculate the burning rates of multimodal propellants is also presented. Results are shown in the form of representative burning rate curves, comparisons with data, and calculated internal details of interest. Ideas for future work are discussed in an Appendix.

NOS1 mediates AP1 nuclear translocation and inflammatory response.

PubMed

Srivastava, Mansi; Baig, Mirza S

2018-06-01

A hallmark of the AP1 functioning is its nuclear translocation, which induces proinflammatory cytokine expression and hence the inflammatory response. After endotoxin shock AP1 transcription factor, which comprises Jun, ATF2, and Fos family of proteins, translocates into the nucleus and induces proinflammatory cytokine expression. In the current study, we found, NOS1 inhibition prevents nuclear translocation of the AP1 transcription factor subunits. Pharmacological inhibition of NOS1 impedes translocation of subunits into the nucleus, suppressing the transcription of inflammatory genes causing a diminished inflammatory response. In conclusion, the study shows the novel mechanism of NOS1- mediated AP1 nuclear translocation, which needs to be further explored. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

49 CFR 1.17 - OST Line of Secretarial Succession.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 1 2012-10-01 2012-10-01 false OST Line of Secretarial Succession. 1.17 Section 1.17 Transportation Office of the Secretary of Transportation ORGANIZATION AND DELEGATION OF POWERS AND DUTIES Office of the Secretary § 1.17 OST Line of Secretarial Succession. (a) The following officials, in...

49 CFR 1.17 - OST Line of Secretarial Succession.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 1 2014-10-01 2014-10-01 false OST Line of Secretarial Succession. 1.17 Section 1.17 Transportation Office of the Secretary of Transportation ORGANIZATION AND DELEGATION OF POWERS AND DUTIES Office of the Secretary § 1.17 OST Line of Secretarial Succession. (a) The following officials, in...

49 CFR 1.17 - OST Line of Secretarial Succession.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false OST Line of Secretarial Succession. 1.17 Section 1.17 Transportation Office of the Secretary of Transportation ORGANIZATION AND DELEGATION OF POWERS AND DUTIES Office of the Secretary § 1.17 OST Line of Secretarial Succession. (a) The following officials, in...

QSO Emission Lines and the Black Hole-Galaxy Bulge Relation

NASA Astrophysics Data System (ADS)

Shields, G. A.; Gebhardt, K.; Salviander, S.; Wills, B. J.; Yuan, M.; Xie, B.; Dietrich, M.

2002-05-01

Supermassive black holes in galactic nuclei have masses closely related to the properties of the host galaxy bulge. In particular, MBH varies as the fourth power of σ , the stellar velocity dispersion (Tremaine et al. 2002, ApJ in press, and references therein). The origin of the black hole-bulge relation is unknown, although theoretical suggestions abound. An important clue would be provided by knowledge of how the relation has evolved over cosmic time. This requires measurement of black hole masses and galactic potentials at large look-back times, which is difficult to do directly. However, black hole masses may be derived from the continuum luminosity and the widths of the broad Balmer lines of QSOs (e.g., Kaspi et al. 2000, ApJ 533, 631), and σ may be derived from the widths of the narrow [O III] lines (Nelson 2000, ApJ, 544, L91). We have carried out this program for a set of published and unpublished observations of Seyfert galaxies and QSOs. Results for low redshift objects support the use of this method to derive MBH and σ . The few available measurements of high redshift QSOs are consistent little or no change in the MBH-σ relation between the present and redshifts up to z = 3.3, when the universe was only two billion years old. This material is based in part upon work supported by the Texas Advanced Research Program under Grant No. 003658-0177-2001.

Incorporating Ninth-Grade PSAT/NMSQT® Scores into AP Potential™ Predictions for AP® European History and AP World History. Statistical Report 2014-1

ERIC Educational Resources Information Center

Zhang, Xiuyuan; Patel, Priyank; Ewing, Maureen

2015-01-01

Historically, AP Potential™ correlations and expectancy tables have been based on 10th-and 11th-grade PSAT/NMSQT® examinees and 11th-and 12th-grade AP® examinees for all subjects (Zhang, Patel, & Ewing,2014; Ewing, Camara, & Millsap, 2006; Camara & Millsap, 1998). However, a large number of students take AP European History and AP…

Isolation and characterization of diadenosine tetraphosphate (Ap4A) hydrolase from Schizosaccharomyces pombe.

PubMed

Robinson, A K; de la Peña, C E; Barnes, L D

1993-02-13

An enzyme that catalyzes the asymmetric hydrolysis of Ap4A has been partially purified from the fission yeast, Schizosaccharomyces pombe. The crude supernatant fraction from log-phase cells was fractionated by (NH4)2SO4 precipitation followed by chromatography on DEAE-cellulose, Red A dye-ligand and QAE-Sepharose resins. Two peaks of Ap4A hydrolase activity, designated major and minor, were separated on the Red A dye-ligand resin. Both the major and minor Ap4A hydrolase have an apparent molecular mass of 49 kDa based on gel filtration chromatography. On a SDS polyacrylamide gel, a protein of 22 kDa exhibited Ap4A hydrolase activity. Both forms of the enzyme have a Km value in the range of 22 to 36 microM for Ap4A. Both forms of the enzyme asymmetrically hydrolyze Ap4A to AMP and ATP as determined by HPLC. Ap4A is the optimal substrate among several nucleotides and dinucleoside polyphosphates tested at 10 microM. A divalent metal cation is required for activity. Concentrations of Pi below 30 mM stimulate Ap4A hydrolase while higher concentrations inhibit the activity. Pi is not a substrate for this Ap4A-degradative enzyme. Fluoride, from 50 microM to 20 mM, has no significant effect on Ap4A hydrolase activity.

AP: A Critical Examination of the Advanced Placement Program

ERIC Educational Resources Information Center

Sadler, Philip M.; Sonnert, Gerhard; Tai, Robert; Klopfenstein, Kirstin

2016-01-01

The Advanced Placement (AP) program was created to enhance the experience of gifted students as they transition from high school to college. "AP: A Critical Examination of the Advanced Placement Program," edited by Philip M. Sadler, Gerhard Sonnert, Robert Tai, and Kirstin Klopfenstein (2010, Harvard Education Press), questions the…

AP Studio Art as an Enabling Constraint for Secondary Art Education

ERIC Educational Resources Information Center

Graham, Mark A.

2009-01-01

Advanced Placement (AP) Studio Art is an influential force in secondary art education as is evident in the 31,800 portfolios submitted for review in 2008. From the perspectives of a high school educator and AP Reader, this author has observed how the constraints of the AP program can be used to generate support for high school art programs and…

MULTI-OBJECTIVE ONLINE OPTIMIZATION OF BEAM LIFETIME AT APS

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

Sun, Yipeng

In this paper, online optimization of beam lifetime at the APS (Advanced Photon Source) storage ring is presented. A general genetic algorithm (GA) is developed and employed for some online optimizations in the APS storage ring. Sextupole magnets in 40 sectors of the APS storage ring are employed as variables for the online nonlinear beam dynamics optimization. The algorithm employs several optimization objectives and is designed to run with topup mode or beam current decay mode. Up to 50\\% improvement of beam lifetime is demonstrated, without affecting the transverse beam sizes and other relevant parameters. In some cases, the top-upmore » injection efficiency is also improved.« less

Shuttle APS propellant thermal conditioner study

NASA Technical Reports Server (NTRS)

Pearson, W. E.

1971-01-01

A study program was performed to allow selection of thermal conditioner assemblies for superheating O2 and H2 at supercritical pressures. The application was the auxiliary propulsion system (APS) for the space shuttle vehicle. The O2/H2 APS propellant feed system included propellant conditioners, of which the thermal conditioner assemblies were a part. Cryogens, pumped to pressures above critical, were directed to the thermal conditioner assembly included: (1) a gas generator assembly with ignition system and bipropellant valves, which burned superheated O2 and H2 at rich conditions; (2) a heat exchanger assembly for thermal conditioning of the cryogenic propellant; and (3) a dump nozzle for heat exchanger exhaust.

HIV-1 Nef-induced Down-Regulation of MHC Class I Requires AP-1 and Clathrin but Not PACS-1 and Is Impeded by AP-2

PubMed Central

Lubben, Nienke B.; Sahlender, Daniela A.; Motley, Alison M.; Lehner, Paul J.; Benaroch, Philippe

2007-01-01

Major histocompatibility complex class I is down-regulated from the surface of human immunodeficiency virus (HIV)-1-infected cells by Nef, a virally encoded protein that is thought to reroute MHC-I to the trans-Golgi network (TGN) in a phosphofurin acidic cluster sorting protein (PACS) 1, adaptor protein (AP)-1, and clathrin-dependent manner. More recently, an alternative model has been proposed, in which Nef uses AP-1 to direct MHC-I to endosomes and lysosomes. Here, we show that knocking down either AP-1 or clathrin with small interfering RNA inhibits the down-regulation of HLA-A2 (an MHC-I isotype) by Nef in HeLa cells. However, knocking down PACS-1 has no effect, not only on Nef-induced down-regulation of HLA-A2 but also on the localization of other proteins containing acidic cluster motifs. Surprisingly, knocking down AP-2 actually enhances Nef activity. Immuno-electron microscopy labeling of Nef-expressing cells indicates that HLA-A2 is rerouted not to the TGN, but to endosomes. In AP-2–depleted cells, more of the HLA-A2 localizes to the inner vesicles of multivesicular bodies. We propose that depleting AP-2 potentiates Nef activity by altering the membrane composition and dynamics of endosomes and causing increased delivery of HLA-A2 to a prelysosomal compartment. PMID:17581864

The History of the APS Topical Group on Shock Compression of Condensed Matter

NASA Astrophysics Data System (ADS)

Forbes, Jerry W.

2002-07-01

In order to provide broader scientific recognition and to advance the science of shock compressed condensed matter, a group of American Physical Society (APS) members worked within the Society to make this field an active part of the APS. Individual papers were presented at APS meetings starting in the 1940's and shock wave sessions were organized starting with the 1967 Pasadena meeting. Shock wave topical conferences began in 1979 in Pullman, WA. Signatures were obtained on a petition in 1984 from a balanced cross-section of the shock wave community to form an APS Topical Group (TG). The APS Council officially accepted the formation of the Shock Compression of Condensed Matter (SCCM) TG at its October 1984 meeting. This action firmly aligned the shock wave field with a major physical science organization. Most early topical conferences were sanctioned by the APS while those held after 1992 were official APS meetings. The topical group organizes a shock wave topical conference in odd numbered years while participating in shock wave/high pressure sessions at APS general meetings in even numbered years.

Diadenosine tetraphosphate (Ap4A) - an E. coli alarmone or a damage metabolite?

PubMed

Despotović, Dragana; Brandis, Alexander; Savidor, Alon; Levin, Yishai; Fumagalli, Laura; Tawfik, Dan S

2017-07-01

Under stress, metabolism is changing: specific up- or down-regulation of proteins and metabolites occurs as well as side effects. Distinguishing specific stress-signaling metabolites (alarmones) from side products (damage metabolites) is not trivial. One example is diadenosine tetraphosphate (Ap4A) - a side product of aminoacyl-tRNA synthetases found in all domains of life. The earliest observations suggested that Ap4A serves as an alarmone for heat stress in Escherichia coli. However, despite 50 years of research, the signaling mechanisms associated with Ap4A remain unknown. We defined a set of criteria for distinguishing alarmones from damage metabolites to systematically classify Ap4A. In a nutshell, no indications for a signaling cascade that is triggered by Ap4A were found; rather, we found that Ap4A is efficiently removed in a constitutive, nonregulated manner. Several fold perturbations in Ap4A concentrations have no effect, yet accumulation at very high levels is toxic due to disturbance of zinc homeostasis, and also because Ap4A's structural overlap with ATP can result in spurious binding and inactivation of ATP-binding proteins. Overall, Ap4A met all criteria for a damage metabolite. While we do not exclude any role in signaling, our results indicate that the damage metabolite option should be considered as the null hypothesis when examining Ap4A and other metabolites whose levels change upon stress. © 2017 Federation of European Biochemical Societies.

Raising Rigor, Getting Results: Lessons Learned from AP Expansion

ERIC Educational Resources Information Center

Wakelyn, David

2009-01-01

Advanced Placement (AP), which enables high school students to take introductory college-level courses, is the nation's oldest example of a rigorous, common curriculum. Students who score well on AP exams are more likely to persist in college and earn a degree. The Advanced Placement Expansion project of the National Governors Association Center…

Data-Based Decision Making: The Road to AP Equity

ERIC Educational Resources Information Center

Edwards, Kelcey; Duggan, Odette

2012-01-01

Presented at the Advanced Placement Annual Conference (APAC) in Lake Buena Vista, FL in July 2012. This presentation reviews concepts central to achieving equitable AP access and success for all willing and academically prepared students. We analyze trends in participation and performance by race/ethnicity from the AP Report to the Nation and…

Transport of poly(acrylic acid) coated 2-line ferrihydrite nanoparticles in saturated aquifer sediments for environmental remediation

NASA Astrophysics Data System (ADS)

Xiang, Aishuang; Zhou, Sheng; Koel, Bruce E.; Jaffé, Peter R.

2014-04-01

Groundwater remediation using iron oxide and zero-valent iron nanoparticles (NPs) can be effective, but is limited in many applications due to the NP strong retention in groundwater-saturated porous media after injection, the passivation of the porous surface, and the high cost of nanomaterials versus macro scale iron. In this study, we investigated transport of bare and polymer-coated 2-line ferrihydrite NPs (30-300 nm) in saturated aquifer sediments. The influence of poly(acrylic acid) (PAA) polymer coatings was studied on the colloidal stability and transport in sediments packed column tests simulating groundwater flow in saturated sediments. In addition, the influence of calcium cations was investigated by transport measurements using sediments with calcium concentrations in the aqueous phase ranging from 0.5 (typical for most sediments) to 2 mM. Measurements were also made of zeta potential, hydrodynamic diameter, polymer adsorption and desorption properties, and bio-availability of PAA-coated NPs. We found that NP transport through the saturated aquifer sediments was improved by PAA coating and that the transport properties could be tuned by adjusting the polymer concentration. We further discovered that PAA coatings enhanced NP transport, compared to bare NPs, in all calcium-containing experiments tested, however, the presence of calcium always exhibited a negative effect on NP transport. In tests of bioavailability, the iron reduction rate of the coated and bare NPs by Geobacter sulfurreducens was the same, which shows that the PAA coating does not significantly reduce NP Fe(III) bioavailability. Our results demonstrate that much improved transport of iron oxide NP can be achieved in saturated aquifer sediments by introducing negatively charged polyelectrolytes and optimizing polymer concentrations, and furthermore, these coated NPs retain their bioavailability that is needed for applications in bio-environmental remediation.

The magnetic field of the double-lined spectroscopic binary system HD 5550

NASA Astrophysics Data System (ADS)

Alecian, E.; Tkachenko, A.; Neiner, C.; Folsom, C. P.; Leroy, B.

2016-05-01

Context. The origin of fossil fields in intermediate- and high-mass stars is poorly understood, as is the interplay between binarity and magnetism during stellar evolution. Thus we have begun a study of the magnetic properties of a sample of intermediate-mass and massive short-period binary systems as a function of binarity properties. Aims: This paper specifically aims to characterise the magnetic field of HD 5550, a double-lined spectroscopic binary system of intermediate mass. Methods: We gathered 25 high-resolution spectropolarimetric observations of HD 5550 using the instrument Narval. We first fitted the intensity spectra using Zeeman/ATLAS9 LTE synthetic spectra to estimate the effective temperatures, microturbulent velocities, and the abundances of some elements of both components, as well as the light ratio of the system. We then applied the multi-line least-square deconvolution (LSD) technique to the intensity and circularly polarised spectra, which provided us with mean LSD I and V line profiles. We fitted the Stokes I line profiles to determine the radial and projected rotational velocities of both stars. We then analysed the shape and evolution of the V profiles using the oblique rotator model to characterise the magnetic fields of both stars. Results: We confirm the Ap nature of the primary, which has previously been reported, and find that the secondary displays spectral characteristics typical of an Am star. While a magnetic field is clearly detected in the lines of the primary, no magnetic field is detected in the secondary in any of our observations. If a dipolar field were present at the surface of the Am star, its polar strength must be below 40 G. The faint variability observed in the Stokes V profiles of the Ap star allowed us to propose a rotation period of 6.84-0.39+0.61 d, which is close to the orbital period (~6.82 d), suggesting that the star is synchronised with its orbit. By fitting the variability of the V profiles, we propose that the

Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus.

PubMed

Mutso, Margit; Morro, Ainhoa Moliner; Smedberg, Cecilia; Kasvandik, Sergo; Aquilimeba, Muriel; Teppor, Mona; Tarve, Liisi; Lulla, Aleksei; Lulla, Valeria; Saul, Sirle; Thaa, Bastian; McInerney, Gerald M; Merits, Andres; Varjak, Margus

2018-04-27

Infection by Chikungunya virus (CHIKV) of the Old World alphaviruses (family Togaviridae) in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP) (nsP1, nsp2, nsP3 and nsP4) that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD) of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established. Using quantitative proteomics, it was found that CHIKV nsP3 HVD can bind cytoskeletal proteins, including CD2AP, SH3KBP1, CAPZA1, CAPZA2 and CAPZB. The interaction with CD2AP was found to be most evident; its binding site was mapped to the second SH3 ligand-like element in nsP3 HVD. Further assessment indicated that CD2AP can bind to nsP3 HVDs of many different New and Old World alphaviruses. Mutation of the short binding element hampered the ability of the virus to establish infection. The mutation also abolished ability of CD2AP to co-localise with nsP3 and replication complexes of CHIKV; the same was observed for Semliki Forest virus (SFV) harbouring a similar mutation. Similar to CD2AP, its homolog SH3KBP1 also bound the identified motif in CHIKV and SFV nsP3.

Transfected MDCK cell line with enhanced expression of CYP3A4 and P-glycoprotein as a model to study their role in drug transport and metabolism.

PubMed

Kwatra, Deep; Budda, Balasubramanyam; Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K

2012-07-02

The aim of this study was to characterize and utilize MDCK cell line expressing CYP3A4 and P-glycoprotein as an in vitro model for evaluating drug-herb and drug-drug of abuse interactions. MDCK cell line simultaneously expressing P-gp and CYP3A4 (MMC) was developed and characterized by using expression and activity studies. Cellular transport study of 200 μM cortisol was performed to determine their combined activity. The study was carried across MDCK-WT, MDCK-MDR1 and MMC cell lines. Similar studies were also carried out in the presence of 50 μM naringin and 3 μM morphine. Samples were analyzed by HPLC for drug and its CYP3A4 metabolite. PCR, qPCR and Western blot studies confirmed the enhanced expression of the proteins in the transfected cells. The Vivid CYP3A4 assay and ketoconazole inhibition studies further confirmed the presence of active protein. Apical to basal transport of cortisol was found to be 10- and 3-fold lower in MMC as compared to MDCK-WT and MDCK-MDR1 respectively. Higher amount of metabolite was formed in MMC than in MDCK-WT, indicating enhanced expression of CYP3A4. Highest cortisol metabolite formation was observed in MMC cell line due to the combined activities of CYP3A4 and P-gp. Transport of cortisol increased 5-fold in the presence of naringin in MMC and doubled in MDCK-MDR1. Cortisol transport in MMC was significantly lower than that in MDCK-WT in the presence of naringin. The permeability increased 3-fold in the presence of morphine, which is a weaker inhibitor of CYP3A4. Formation of 6β-hydroxy cortisol was found to decrease in the presence of morphine and naringin. This new model cell line with its enhanced CYP3A4 and P-gp levels in addition to short culture time can serve as an invaluable model to study drug-drug interactions. This cell line can also be used to study the combined contribution of efflux transporter and metabolizing enzymes toward drug-drug interactions.

TRANSFECTED MDCK CELL LINE WITH ENHANCED EXPRESSION OF CYP3A4 AND P-GLYCOPROTEIN AS A MODEL TO STUDY THEIR ROLE IN DRUG TRANSPORT AND METABOLISM

PubMed Central

Kwatra, Deep; Budda, Balasubramanyam; Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K.

2012-01-01

The aim of this study was to characterize and utilize MDCK cell line expressing CYP3A4 and P-glycoprotein as an in vitro model for evaluating drug-herb and drug-drugs of abuse interactions. MDCK cell line simultaneously expressing P-gp and CYP3A4 (MMC) was developed and characterized by using expression and activity studies. Cellular transport study of 200 μM cortisol was performed to determine their combined activity. The study was carried across MDCK-WT, MDCK-MDR1 and MMC cell lines. Similar studies were also carried out in the presence of 50 μM naringin and 3 μM morphine. Samples were analyzed by HPLC for drug and its CYP3A4 metabolite. PCR, qPCR and western blot studies confirmed the enhanced expression of the proteins in the transfected cells. The vivid CYP3A4 assay and ketoconazole inhibition studies further confirmed the presence of active protein. Apical to basal transport of cortisol was found to be ten and three fold lower in MMC as compared to WT and MDCKMDR1 respectively. Higher amount of metabolite was formed in MMC than in MDCK-WT indicating enhanced expression of CYP3A4. Highest cortisol metabolite formation was observed in MMC cell line due to the combined metabolic activities of CYP3A4 and P-gp. Transport of cortisol increased fivefold in presence of naringin in MMC and doubled in MDCKMDR1. Cortisol transport in MMC was significantly lower than that in WT in presence of naringin. The permeability increased three fold in presence of morphine which is a weaker inhibitor of CYP3A4. Formation of 6β-hydroxy cortisol was found to decrease in presence of morphine and naringin. This new model cell line with its enhanced CYP3A4 and P-gp levels in addition to short culture time can serve as an invaluable model to study drug-drug interactions. This cell line can also be used to study the combined contribution of efflux transporter and metabolizing enzymes towards drug-drug interactions. PMID:22676443

The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

PubMed Central

Diccianni, M B; Imagawa, M; Muramatsu, M

1992-01-01

Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis. Images PMID:1408831

The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

PubMed

Diccianni, M B; Imagawa, M; Muramatsu, M

1992-10-11

Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis.

A New lncRNA, APTR, Associates with and Represses the CDKN1A/p21 Promoter by Recruiting Polycomb Proteins

PubMed Central

Negishi, Masamitsu; Wongpalee, Somsakul P.; Sarkar, Sukumar; Park, Jonghoon; Lee, Kyung Yong; Shibata, Yoshiyuki; Reon, Brian J.; Abounader, Roger; Suzuki, Yutaka; Sugano, Sumio; Dutta, Anindya

2014-01-01

Long noncoding RNAs (lncRNAs) have emerged as a major regulator of cell physiology, but many of which have no known function. CDKN1A/p21 is an important inhibitor of the cell-cycle, regulator of the DNA damage response and effector of the tumor suppressor p53, playing a crucial role in tumor development and prevention. In order to identify a regulator for tumor progression, we performed an siRNA screen of human lncRNAs required for cell proliferation, and identified a novel lncRNA, APTR, that acts in trans to repress the CDKN1A/p21 promoter independent of p53 to promote cell proliferation. APTR associates with the promoter of CDKN1A/p21 and this association requires a complementary-Alu sequence encoded in APTR. A different module of APTR associates with and recruits the Polycomb repressive complex 2 (PRC2) to epigenetically repress the p21 promoter. A decrease in APTR is necessary for the induction of p21 after heat stress and DNA damage by doxorubicin, and the levels of APTR and p21 are anti-correlated in human glioblastomas. Our data identify a new regulator of the cell-cycle inhibitor CDKN1A/p21 that acts as a proliferative factor in cancer cell lines and in glioblastomas and demonstrate that Alu elements present in lncRNAs can contribute to targeting regulatory lncRNAs to promoters. PMID:24748121

Crystal structures of eosinophil-derived neurotoxin (EDN) in complex with the inhibitors 5'-ATP, Ap3A, Ap4A, and Ap5A.

PubMed

Baker, Matthew D; Holloway, Daniel E; Swaminathan, G Jawahar; Acharya, K Ravi

2006-01-17

Eosinophil-derived neurotoxin (EDN) is a catalytically proficient member of the pancreatic ribonuclease superfamily secreted along with other eosinophil granule proteins during innate host defense responses and various eosinophil-related inflammatory and allergic diseases. The ribonucleolytic activity of EDN is central to its antiviral and neurotoxic activities and possibly to other facets of its biological activity. To probe the importance of this enzymatic activity further, specific inhibitors will be of great aid. Derivatives of 5'-ADP are among the most potent inhibitors currently known. Here, we use X-ray crystallography to investigate the binding of four natural nucleotides containing this moiety. 5'-ATP binds in two alternative orientations, one occupying the B2 subsite in a conventional manner and one being a retro orientation with no ordered adenosine moiety. Diadenosine triphosphate (Ap3A) and diadenosine tetraphosphate (Ap4A) bind with one adenine positioned at the B2 subsite, the polyphosphate chain extending across the P1 subsite in an ill-defined conformation, and a disordered second adenosine moiety. Diadenosine pentaphosphate (Ap5A), the most avid inhibitor of this series, binds in a completely ordered fashion with one adenine positioned conventionally at the B2 subsite, the polyphosphate chain occupying the P1 and putative P(-1) subsites, and the other adenine bound in a retro-like manner at the edge of the B1 subsite. The binding mode of each of these inhibitors has features seen in previously determined structures of adenosine diphosphates. We examine the structure-affinity relationships of these inhibitors and discuss the implications for the design of improved inhibitors.

Modeling Instruction in AP Physics C: Mechanics and Electricity and Magnetism

NASA Astrophysics Data System (ADS)

Belcher, Nathan Tillman

This action research study used data from multiple assessments in Mechanics and Electricity and Magnetism to determine the viability of Modeling Instruction as a pedagogy for students in AP Physics C: Mechanics and Electricity and Magnetism. Modeling Instruction is a guided-inquiry approach to teaching science in which students progress through the Modeling Cycle to develop a fully-constructed model for a scientific concept. AP Physics C: Mechanics and Electricity and Magnetism are calculus-based physics courses, approximately equivalent to first-year calculus-based physics courses at the collegiate level. Using a one-group pretest-posttest design, students were assessed in Mechanics using the Force Concept Inventory, Mechanics Baseline Test, and 2015 AP Physics C: Mechanics Practice Exam. With the same design, students were assessed in Electricity and Magnetism on the Brief Electricity and Magnetism Assessment, Electricity and Magnetism Conceptual Assessment, and 2015 AP Physics C: Electricity and Magnetism Practice Exam. In a one-shot case study design, student scores were collected from the 2017 AP Physics C: Mechanics and Electricity and Magnetism Exams. Students performed moderately well on the assessments in Mechanics and Electricity and Magnetism, demonstrating that Modeling Instruction is a viable pedagogy in AP Physics C: Electricity and Magnetism.

RelAp43, a member of the NF-κB family involved in innate immune response against Lyssavirus infection.

PubMed

Luco, Sophie; Delmas, Olivier; Vidalain, Pierre-Olivier; Tangy, Frédéric; Weil, Robert; Bourhy, Hervé

2012-01-01

NF-κB transcription factors are crucial for many cellular processes. NF-κB is activated by viral infections to induce expression of antiviral cytokines. Here, we identified a novel member of the human NF-κB family, denoted RelAp43, the nucleotide sequence of which contains several exons as well as an intron of the RelA gene. RelAp43 is expressed in all cell lines and tissues tested and exhibits all the properties of a NF-κB protein. Although its sequence does not include a transactivation domain, identifying it as a class I member of the NF-κB family, it is able to potentiate RelA-mediated transactivation and stabilize dimers comprising p50. Furthermore, RelAp43 stimulates the expression of HIAP1, IRF1, and IFN-β - three genes involved in cell immunity against viral infection. It is also targeted by the matrix protein of lyssaviruses, the agents of rabies, resulting in an inhibition of the NF-κB pathway. Taken together, our data provide the description of a novel functional member of the NF-κB family, which plays a key role in the induction of anti-viral innate immune response.

RelAp43, a Member of the NF-κB Family Involved in Innate Immune Response against Lyssavirus Infection

PubMed Central

Vidalain, Pierre-Olivier; Tangy, Frédéric; Weil, Robert; Bourhy, Hervé

2012-01-01

NF-κB transcription factors are crucial for many cellular processes. NF-κB is activated by viral infections to induce expression of antiviral cytokines. Here, we identified a novel member of the human NF-κB family, denoted RelAp43, the nucleotide sequence of which contains several exons as well as an intron of the RelA gene. RelAp43 is expressed in all cell lines and tissues tested and exhibits all the properties of a NF-κB protein. Although its sequence does not include a transactivation domain, identifying it as a class I member of the NF-κB family, it is able to potentiate RelA-mediated transactivation and stabilize dimers comprising p50. Furthermore, RelAp43 stimulates the expression of HIAP1, IRF1, and IFN-β - three genes involved in cell immunity against viral infection. It is also targeted by the matrix protein of lyssaviruses, the agents of rabies, resulting in an inhibition of the NF-κB pathway. Taken together, our data provide the description of a novel functional member of the NF-κB family, which plays a key role in the induction of anti-viral innate immune response. PMID:23271966

The effect of turbulence strength on meandering field lines and Solar Energetic Particle event extents

NASA Astrophysics Data System (ADS)

Laitinen, Timo; Effenberger, Frederic; Kopp, Andreas; Dalla, Silvia

2018-02-01

Insights into the processes of Solar Energetic Particle (SEP) propagation are essential for understanding how solar eruptions affect the radiation environment of near-Earth space. SEP propagation is influenced by turbulent magnetic fields in the solar wind, resulting in stochastic transport of the particles from their acceleration site to Earth. While the conventional approach for SEP modelling focuses mainly on the transport of particles along the mean Parker spiral magnetic field, multi-spacecraft observations suggest that the cross-field propagation shapes the SEP fluxes at Earth strongly. However, adding cross-field transport of SEPs as spatial diffusion has been shown to be insufficient in modelling the SEP events without use of unrealistically large cross-field diffusion coefficients. Recently, Laitinen et al. [ApJL 773 (2013b); A&A 591 (2016)] demonstrated that the early-time propagation of energetic particles across the mean field direction in turbulent fields is not diffusive, with the particles propagating along meandering field lines. This early-time transport mode results in fast access of the particles across the mean field direction, in agreement with the SEP observations. In this work, we study the propagation of SEPs within the new transport paradigm, and demonstrate the significance of turbulence strength on the evolution of the SEP radiation environment near Earth. We calculate the transport parameters consistently using a turbulence transport model, parametrised by the SEP parallel scattering mean free path at 1 AU, λ∥*, and show that the parallel and cross-field transport are connected, with conditions resulting in slow parallel transport corresponding to wider events. We find a scaling σφ,max∝(1/λ∥*)1/4 for the Gaussian fitting of the longitudinal distribution of maximum intensities. The longitudes with highest intensities are shifted towards the west for strong scattering conditions. Our results emphasise the importance of

Molecular Basis for Enhancement of the Meiotic DMCI Recombinase by RAD51AP1

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

Dray, Eloise; Dunlop, Myun Hwa; Kauppi, Liisa

Homologous recombination is needed for meiotic chromosome segregation, genome maintenance, and tumor suppression. RAD51AP1 (RAD51 Associated Protein 1) has been shown to interact with and enhance the recombinase activity of RAD51. Accordingly, genetic ablation of RAD51AP1 leads to enhanced sensitivity to and also chromosome aberrations upon DNA damage, demonstrating a role for RAD51AP1 in mitotic homologous recombination. Here we show physical association of RAD51AP1 with the meiosis-specific recombinase DMC1 and a stimulatory effect of RAD51AP1 on the DMC1-mediated D-loop reaction. Mechanistic studies have revealed that RAD51AP1 enhances the ability of the DMC1 presynaptic filament to capture the duplex DNA partnermore » and to assemble the synaptic complex, in which the recombining DNA strands are homologously aligned. We also provide evidence that functional co-operation is dependent on complex formation between DMC1 and RAD51AP1, and that distinct epitopes in RAD51AP1 mediate interactions with RAD51 and DMC1. Finally, we show that RAD51AP1 is expressed in mouse testes, and that RAD51AP1 foci co-localize with a subset of DMC1 foci in spermatocytes. These results suggest that RAD51AP1 also serves an important role in meiotic homologous recombination.« less

Implementation and Initial Validation of the APS English Test [and] The APS English-Writing Test at Golden West College: Evidence for Predictive Validity.

ERIC Educational Resources Information Center

Isonio, Steven

In May 1991, Golden West College (California) conducted a validation study of the English portion of the Assessment and Placement Services for Community Colleges (APS), followed by a predictive validity study in July 1991. The initial study was designed to aid in the implementation of the new test at GWC by comparing data on APS use at other…

Directionality of Flare-Accelerated Particles from γ -ray Lines

NASA Astrophysics Data System (ADS)

Share, G. H.; Murphy, R. J.

2000-05-01

The energies and widths of γ -ray lines emitted by ambient nuclei excited by flare-accelerated protons and α -particles provide information on their directionality, spectra, and on the uniformity of the interaction region. For example, the γ -rays observed from a downward beam of particles impacting at 0o heliocentric angle would exhibit a clear Doppler red-shift and some broadening, dependent on the spectrum of the particles. In contrast, γ -rays observed from the same beam of particles impacting at 90o would be neither observably shifted nor broadened. We have studied the energies and widths of strong lines from de-excitations of 20Ne, 12C, and 16O in solar flares as a function of heliocentric angle. We use spectra from 21 flares observed with NASA's Solar Maximum Mission/GRS and Compton Observatory/OSSE experiments. The line energies of all three nuclei exhibit ~0.9% red-shifts from their laboratory values for flares observed at heliocentric angles <40o. In contrast, the energies are not significantly shifted for flares observed at angles >80o. The lines at all heliocentric angles are broadened between ~2.5% to 4%. These results are suggestive of a broad downward distribution of accelerated particles in flares or an isotropic distribution in a medium that has a significant density gradient. Detailed comparisons of these data with results from the gamma-ray production code (Ramaty, et al. 1979, ApJS, 40, 487; Murphy, et al. 1991, ApJ, 371, 793) are required in order to place constraints on the angular distributions of particles. This research has been supported by NASA grant W-18995.

AP-102/104 Retrieval control system qualification test procedure

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

RIECK, C.A.

1999-05-18

This Qualification Test Procedure documents the results of the qualification testing that was performed on the Project W-211, ''Initial Tank Retrieval Systems,'' retrieval control system (RCS) for tanks 241-AP-102 and 241-AP-104. The results confirm that the RCS has been programmed correctly and that the two related hardware enclosures have been assembled in accordance with the design documents.

Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1.

PubMed

Eriksson, Daniel; Dalin, Frida; Eriksson, Gabriel Nordling; Landegren, Nils; Bianchi, Matteo; Hallgren, Åsa; Dahlqvist, Per; Wahlberg, Jeanette; Ekwall, Olov; Winqvist, Ola; Catrina, Sergiu-Bogdan; Rönnelid, Johan; Hulting, Anna-Lena; Lindblad-Toh, Kerstin; Alimohammadi, Mohammad; Husebye, Eystein S; Knappskog, Per Morten; Rosengren Pielberg, Gerli; Bensing, Sophie; Kämpe, Olle

2018-01-01

Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1. To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease. We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE. In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure. We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications. Copyright © 2017 Endocrine Society

Curcumin modulates cellular AP-1, NF-kB, and HPV16 E6 proteins in oral cancer.

PubMed

Mishra, Alok; Kumar, Rakesh; Tyagi, Abhishek; Kohaar, Indu; Hedau, Suresh; Bharti, Alok C; Sarker, Subhodeep; Dey, Dipankar; Saluja, Daman; Das, Bhudev

2015-01-01

In this study, we investigated the effects of the natural antioxidant curcumin on the HPV16-positive oral carcinoma cell line 93VU147T and demonstrated that curcumin is not only a potent inhibitor for the activity of host nuclear transcription factors AP-1 and NF-kB but it also selectively suppresses transcription of the HPV16/E6 oncogene during the carcinogenic process in oral cancer cells. This study suggests a therapeutic potential of curcumin for high-risk human papilloma virus (HPV)-infected oral cancers.

Curcumin modulates cellular AP-1, NF-kB, and HPV16 E6 proteins in oral cancer

PubMed Central

Mishra, Alok; Kumar, Rakesh; Tyagi, Abhishek; Kohaar, Indu; Hedau, Suresh; Bharti, Alok C; Sarker, Subhodeep; Dey, Dipankar; Saluja, Daman; Das, Bhudev

2015-01-01

In this study, we investigated the effects of the natural antioxidant curcumin on the HPV16-positive oral carcinoma cell line 93VU147T and demonstrated that curcumin is not only a potent inhibitor for the activity of host nuclear transcription factors AP-1 and NF-kB but it also selectively suppresses transcription of the HPV16/E6 oncogene during the carcinogenic process in oral cancer cells. This study suggests a therapeutic potential of curcumin for high-risk human papilloma virus (HPV)-infected oral cancers. PMID:25932049

Building Reading, Writing and Analysis in the AP U.S. History Classroom

ERIC Educational Resources Information Center

Heller, Stephen; Stacy, Jason

2013-01-01

The building of historical thinking skills has historically been a lonely endeavor for AP U.S. history teachers. Many often generate their own pedagogy, perhaps modified from an AP workshop or generally gleaned from released exam essay questions. However, as currently scheduled, in 2014, the AP U.S. history exam will undergo a redesign that will…

A New Photometric Study of Ap and Am Stars in the Infrared

NASA Astrophysics Data System (ADS)

Chen, P. S.; Liu, J. Y.; Shan, H. G.

2017-05-01

In this paper, 426 well known confirmed Ap and Am stars are photometrically studied in the infrared. The 2MASS, Wide-field Infrared Survey Explorer (WISE), and IRAS data are employed to make analyses. The results in this paper have shown that in the 1-3 μm region over 90% Ap and Am stars have no or little infrared excesses, and infrared radiations in the near-infrared from these stars are probably dominated by the free-free emissions. It is also shown that in the 3-12 μm region, the majority of Ap stars and Am stars have very similar behavior, I.e., in the W1-W2 (3.4-4.6 μm) region, over half of Ap and Am stars have clear infrared excesses, which are possibly due to the binarity, the multiplicity, and/or the debris disk, but in the W2-W3 (4.6-12 μm) region they have no or little infrared excess. In addition, in the 12-22 μm region, some of Ap stars and Am stars show the infrared excesses and infrared radiations for these Ap and Am stars are probably due to the free-free emissions. In addition, it is seen that the probability of being the binarity, the multiplicity and/or the debris disk for Am stars is much higher than that for Ap stars. Furthermore, it can be seen that, in general, no relations can be found between infrared colors and spectral types either for Ap stars or for Am stars.

Glaucoma patients present increased levels of diadenosine tetraphosphate, Ap(4)A, in the aqueous humour.

PubMed

Castany, Marta; Jordi, Isabel; Catala, Jaume; Gual, Arcadi; Morales, Miguel; Gasull, Xavier; Pintor, Jesus

2011-03-01

Previous studies have shown the presence of diadenosine tetraphosphate (Ap(4)A) and pentaphosphate (Ap(5)A) in the aqueous humour (AH) of different species. When topically applied to the rabbit cornea, Ap(4)A decreased IOP while Ap(5)A increased it. Here we study the presence of dinucleoside polyphosphates in the AH from human patients with or without glaucoma. AH was obtained at the time of cataract surgery from patients with (n=16) or without (n=10) primary open-angle glaucoma. AH (0.1-0.2 ml) was collected at the beginning of surgery through a corneal paracentesis and immediately cooled in liquid nitrogen, kept frozen and protected from light. AH aliquots were analyzed by HPLC for the presence of Ap(4)A and Ap(5)A. Both, Ap(4)A and Ap(5)A were detected in the AH of both experimental groups. No significant differences were found for Ap(5)A. In contrast, Ap(4)A levels were increased by ∼15-fold in the AH from glaucomatous eyes ranging from 19.5±9.2 nM in normal individuals to 286.03±30.9 nM in glaucomatous patients. In conclusion, both Ap(4)A and Ap(5)A were detected for the first time in human AH. Interestingly, glaucomatous eyes presented elevated concentrations of Ap(4)A compared to controls. The role of Ap(4)A needs to be elucidated but it may help to protect the autonomic innervation in the ciliary body/trabecular meshwork. Also, because of its higher levels in glaucoma patients it may be considered as a possible glaucoma biomarker. Copyright © 2010 Elsevier Ltd. All rights reserved.

The Iron Abundance of IOTA Herculis From Ultraviolet Iron Lines

NASA Astrophysics Data System (ADS)

Grigsby, J.; Mulliss, C.; Baer, G.

1995-03-01

We have obtained (Adelman 1992, 1993, private comunication) coadded, high-resolution IUE spectra of Iota Herculis (B3 IV) in both short wavelength (SWP) and long wavelength (LWP) regions. The spectra span the ultraviolet spectrum from 110 - 300 nm and have a SNR of roughly 30 -50; they are described in Adelman et. al. (1993, ApJ 419, 276). Abundance indicators were 54 lines of Fe II and 26 lines of Fe III whose atomic parameters have been measured in the laboratory. LTE synthetic spectra for comparison with observations were produced with the Kurucz model atmosphere and spectral synthesis codes ATLAS9/SYNTHE (Kurucz 1979, ApJS 40,1; Kurucz and Avrett 1981, SAO Special Report 391). Model parameters were chosen from the literature: effective temperature = 17500 K, log g =3.75, v sin i= 11 km/s, and turbulent velocity = 0 km/s. (Peters and Polidan 1985, in IAU Symposium 111, ed. D. S. Hayes et al. (Dordrecht: Reidel), 417). We determined the equivalent widths of the chosen lines by fitting gaussian profiles to the lines and by measuring the equivalent widths of the gaussians. We derived abundances by fitting a straight line to a plot of observed equivalent widths vs. synthetic equivalent widths; we adjusted the iron abundance of the models until a slope of unity was achieved. The abundances derived from the different ionization stages are in agreement: Fe II lines indicate an iron abundance that is 34 +15/-10% the solar value([Fe/H]=-0.47 +0.16-0.15dex), while from Fe III lines we obtain 34 +/- 10% ([Fe/H]=-0.47 +0.11/-0.15 dex). A search of the literature suggests that no previous investigations of this star's iron abundance have found agreement between the different ionization stages. We thank Saul Adelman for his generous assistance, and the Faculty Research Fund Board of Wittenberg University for support of this research.

Erratum: ``Chandra HETGS Multiphase Spectroscopy of the Young Magnetic O Star θ1 Orionis C'' (ApJ, 628, 986 [2005])

NASA Astrophysics Data System (ADS)

Gagné, Marc; Oksala, Mary E.; Cohen, David H.; Tonnesen, Stephanie K.; ud-Doula, Asif; Owocki, Stanley P.; Townsend, Richard H. D.; MacFarlane, Joseph J.

2005-11-01

Figure 13 of our paper shows the dependence of the forbidden-to-intercombination line ratio on formation radius and electron density for two He-like ions, Mg XI and S XV, assuming a 45,000 K photosphere. In calculating the PRISMSPECT line ratios, we neglected to include the flux from the upper 3P2-->1S0 transition. For lower-Z ions such as Mg XI, the intercombination doublet is dominated by flux from the lower transition. But for higher-Z elements, this omission led us to underestimate the intercombination line strength from our model. In addition, comparing the spectral type and luminosity of θ1 Ori C with the recent calibrations of P. Massey et al. (ApJ, 628, 986 [2005]) and F. Martins et al. (ApJ, 628, 986 [2005]) suggests that θ1 Ori C is an O5.5 V star with radius R~10.6 Rsolar and effective temperature Teff~40,000 K. This new calibration makes θ1 Ori C larger and cooler than both the ``hot'' and ``cool'' models in Table 3 of our original paper. In the revised Figure 13 below, we show the corrected PRISMSPECT line ratios for Mg XI, Si XIII, and S XV as a function of u=R*/R for Teff=40,000 K. Also shown are the predictions from the analytic parametrization of G. R. Blumenthal et al. (ApJ, 628, 986 [2005]). For Mg XI and Si XIII, we further show the predictions based on the R0 values of D. Porquet et al. (ApJ, 628, 986 [2005]). The hatched regions in Figure 13 represent the 1 σ upper and lower bounds on f/i from the HETG data and u=R*/R from the PRISMSPECT model. Although the three f/i ratios yield different bounds on the formation radius, there is a range of radii, 1.7ApJ, 628, 986 [2005]) (Fig. 13, solid lines), the range of radii is 1.6

Michigan transportation facts & figures : finance

DOT National Transportation Integrated Search

2002-08-16

This on-line document is part of a series, Transportation Facts & Figures, by the Michigan Department of Transportation (MDOT). The Finance section of Transportation Facts & Figures cover such topics as Michigan Transportation Fund, fuel taxes, fuel ...

X-ray optics simulation and beamline design for the APS upgrade

NASA Astrophysics Data System (ADS)

Shi, Xianbo; Reininger, Ruben; Harder, Ross; Haeffner, Dean

2017-08-01

The upgrade of the Advanced Photon Source (APS) to a Multi-Bend Achromat (MBA) will increase the brightness of the APS by between two and three orders of magnitude. The APS upgrade (APS-U) project includes a list of feature beamlines that will take full advantage of the new machine. Many of the existing beamlines will be also upgraded to profit from this significant machine enhancement. Optics simulations are essential in the design and optimization of these new and existing beamlines. In this contribution, the simulation tools used and developed at APS, ranging from analytical to numerical methods, are summarized. Three general optical layouts are compared in terms of their coherence control and focusing capabilities. The concept of zoom optics, where two sets of focusing elements (e.g., CRLs and KB mirrors) are used to provide variable beam sizes at a fixed focal plane, is optimized analytically. The effects of figure errors on the vertical spot size and on the local coherence along the vertical direction of the optimized design are investigated.

Inotropic effects of diadenosine tetraphosphate (AP4A) in human and animal cardiac preparations.

PubMed

Vahlensieck, U; Bokník, P; Gombosová, I; Huke, S; Knapp, J; Linck, B; Lüss, H; Müller, F U; Neumann, J; Deng, M C; Scheld, H H; Jankowski, H; Schlüter, H; Zidek, W; Zimmermann, N; Schmitz, W

1999-02-01

Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse physiological effects in animal systems. However, the effects of AP4A on inotropy in ventricular cardiac preparations have not yet been studied. The effects of AP4A on force of contraction (FOC) were studied in isolated electrically driven guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L-type calcium current and [Ca]i were studied in isolated guinea pig ventricular myocytes. In guinea pig left atria, AP4A (0.1-100 microM) reduced FOC maximally by 36.5 +/- 4.3%. In guinea pig papillary muscles, AP4A (100 microM) alone was ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 +/- 3.4%. The negative inotropic effects of AP4A in atria and papillary muscles were abolished by the A1-adenosine receptor antagonist 1, 3-dipropyl-cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 microM) attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human atrial and ventricular preparations, AP4A (100 microM) alone increased FOC to 158.3 +/- 12.4% and 167.5 +/- 25.1%, respectively. These positive inotropic effects were abolished by the P2-purinoceptor antagonist suramin. On the other hand, AP4A (100 microM) reduced FOC by 27.2 +/- 7.4% in isoproterenol-stimulated human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl-cyclopentylxanthine. In summary, after beta adrenergic stimulation AP4A exerts negative inotropic effects in animal and human ventricular preparations via stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2-purinoceptor stimulation might be a new positive inotropic principle in the human myocardium.

Role of ubiquitin and the HPV E6 oncoprotein in E6AP-mediated ubiquitination

PubMed Central

Mortensen, Franziska; Schneider, Daniel; Barbic, Tanja; Sladewska-Marquardt, Anna; Kühnle, Simone; Marx, Andreas; Scheffner, Martin

2015-01-01

Deregulation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with three different clinical pictures. Hijacking of E6AP by the E6 oncoprotein of distinct human papillomaviruses (HPV) contributes to the development of cervical cancer, whereas loss of E6AP expression or function is the cause of Angelman syndrome, a neurodevelopmental disorder, and increased expression of E6AP has been involved in autism spectrum disorders. Although these observations indicate that the activity of E6AP has to be tightly controlled, only little is known about how E6AP is regulated at the posttranslational level. Here, we provide evidence that the hydrophobic patch of ubiquitin comprising Leu-8 and Ile-44 is important for E6AP-mediated ubiquitination, whereas it does not affect the catalytic properties of the isolated catalytic HECT domain of E6AP. Furthermore, we show that the HPV E6 oncoprotein rescues the disability of full-length E6AP to use a respective hydrophobic patch mutant of ubiquitin for ubiquitination and that it stimulates E6AP-mediated ubiquitination of Ring1B, a known substrate of E6AP, in vitro and in cells. Based on these data, we propose that E6AP exists in at least two different states, an active and a less active or latent one, and that the activity of E6AP is controlled by noncovalent interactions with ubiquitin and allosteric activators such as the HPV E6 oncoprotein. PMID:26216987

Aerosol-delivered programmed cell death 4 enhanced apoptosis, controlled cell cycle and suppressed AP-1 activity in the lungs of AP-1 luciferase reporter mice.

PubMed

Hwang, S-K; Jin, H; Kwon, J T; Chang, S-H; Kim, T H; Cho, C-S; Lee, K H; Young, M R; Colburn, N H; Beck, G R; Yang, H-S; Cho, M-H

2007-09-01

The long-term survival of lung cancer patients treated with conventional therapies remains poor and therefore the need for novel approaches remains high. This has led to the re-emergence of aerosol delivery as a therapeutic intervention. In this study, glucosylated polyethylenimine (GPEI) was used as carrier to investigate programmed cell death 4 (PDCD4) and PDCD4 mutant (D418A), an eIF4A-binding mutant, on PDCD4-related signaling and activator protein-1 (AP-1) activity in the lungs of AP-1 luciferase reporter mice. After confirming the efficiency of GPEI as a carrier in lungs, the effects of aerosol-delivered PDCD4 were investigated in AP-1 luciferase reporter mice. Aerosol delivery of GPEI/PDCD4 through a nose-only inhalation facilitated the apoptosis of lungs whereas aerosol PDCD4 mutant did not. Also, such aerosol delivery regulated proteins relevant to cell-cycle control and suppressed AP-1 activity. Results obtained by western blot analysis, immunohistochemistry, luciferase assay and deoxynucleotidyl-transferase-mediated nick end labeling study suggest that combined actions such as facilitating apoptosis, controlling cell cycle and suppression of AP-1 activity by PDCD4 may provide useful tool for designing lung tumor prevention and treatment by which PDCD4 functions as a transformation suppressor in the future.

APS-U LATTICE DESIGN FOR OFF-AXIS ACCUMULATION

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

Sun, Yipeng; Borland, M.; Lindberg, R.

2017-06-25

A 67-pm hybrid-seven-bend achromat (H7BA) lattice is being proposed for a future Advanced Photon Source (APS) multi-bend-achromat (MBA) upgrade project. This lattice design pushes for smaller emittance and requires use of a swap-out (on-axis) injection scheme due to limited dynamic acceptance. Alternate lattice design work has also been performed for the APS upgrade to achieve better beam dynamics performance than the nominal APS MBA lattice, in order to allow off-axis accumulation. Two such alternate H7BA lattice designs, which target a still-low emittance of 90 pm, are discussed in detail in this paper. Although the single-particle-dynamics performance is good, simulations ofmore » collective effects indicate that surprising difficulty would be expected accumulating high single-bunch charge in this lattice. The brightness of the 90-pm lattice is also a factor of two lower than the 67-pm H7BA lattice.« less

A paradoxical increase of a metabolite upon increased expression of its catabolic enzyme: the case of diadenosine tetraphosphate (Ap4A) and Ap4A phosphorylase I in Saccharomyces cerevisiae.

PubMed Central

Avila, D M; Robinson, A K; Kaushal, V; Barnes, L D

1991-01-01

The APA1 gene in Saccharomyces cerevisiae encodes Ap4A phosphorylase I, the catabolic enzyme for diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A). APA1 has been inserted into a multicopy plasmid and into a centromeric plasmid with a GAL1 promoter. Enhanced expression of APA1 via the plasmids resulted in 10- and 90-fold increases in Ap4A phosphorylase activity, respectively, as assayed in vitro. However, the intracellular concentration of Ap4A exhibited increases of 2- and 15-fold, respectively, from the two different plasmids. Intracellular Ap4A increased 3- to 20-fold during growth on galactose of a transformant with APA1 under the control of the GAL1 promoter. Intracellular adenosine 5'-P1-tetraphospho-P4-5"'-guanosine (Ap4G) and diguanosine 5',5"'-P1,P4-tetraphosphate (Gp4G) also increased in the transformant under these conditions. The chromosomal locus of APA1 has been disrupted in a haploid strain. The Ap4A phosphorylase activity decreased by 80% and the intracellular Ap4A concentration increased by a factor of five in the null mutant. These results with the null mutant agree with previous results reported by Plateau et al. (P. Plateau, M. Fromant, J.-M. Schmitter, J.-M. Buhler, and S. Blancquet, J. Bacteriol. 171:6437-6445, 1989). The paradoxical increase in Ap4A upon enhanced expression of APA1 indicates that the metabolic consequences of altered gene expression may be more complex than indicated solely by assay of enzymatic activity of the gene product. PMID:1660456

A paradoxical increase of a metabolite upon increased expression of its catabolic enzyme: the case of diadenosine tetraphosphate (Ap4A) and Ap4A phosphorylase I in Saccharomyces cerevisiae.

PubMed

Avila, D M; Robinson, A K; Kaushal, V; Barnes, L D

1991-12-01

The APA1 gene in Saccharomyces cerevisiae encodes Ap4A phosphorylase I, the catabolic enzyme for diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A). APA1 has been inserted into a multicopy plasmid and into a centromeric plasmid with a GAL1 promoter. Enhanced expression of APA1 via the plasmids resulted in 10- and 90-fold increases in Ap4A phosphorylase activity, respectively, as assayed in vitro. However, the intracellular concentration of Ap4A exhibited increases of 2- and 15-fold, respectively, from the two different plasmids. Intracellular Ap4A increased 3- to 20-fold during growth on galactose of a transformant with APA1 under the control of the GAL1 promoter. Intracellular adenosine 5'-P1-tetraphospho-P4-5"'-guanosine (Ap4G) and diguanosine 5',5"'-P1,P4-tetraphosphate (Gp4G) also increased in the transformant under these conditions. The chromosomal locus of APA1 has been disrupted in a haploid strain. The Ap4A phosphorylase activity decreased by 80% and the intracellular Ap4A concentration increased by a factor of five in the null mutant. These results with the null mutant agree with previous results reported by Plateau et al. (P. Plateau, M. Fromant, J.-M. Schmitter, J.-M. Buhler, and S. Blancquet, J. Bacteriol. 171:6437-6445, 1989). The paradoxical increase in Ap4A upon enhanced expression of APA1 indicates that the metabolic consequences of altered gene expression may be more complex than indicated solely by assay of enzymatic activity of the gene product.

Clinical application of diadenosine tetraphosphate (Ap4A:F-1500) for controlled hypotension.

PubMed

Kikuta, Y; Ohiwa, E; Okada, K; Watanabe, A; Haruki, S

1999-01-01

In our animal study, it was revealed that diadenosine tetraphosphate (Ap4A:F-1500) has a dose-dependent hypotension effect of up to 60% decrease in mean arterial pressure compared to control value. Furthermore, in healthy male volunteers, the safety of Ap4A up to 4 mg.min-1 was confirmed. In patients who require surgical procedures under general anesthesia together with controlled hypotension, hypotension was induced by Ap4A in order to examine its hypotensive effect and modulating action on the blood pressure. Ten patients who required controlled hypotension and who were scheduled for elective surgery under general anesthesia were studied. Anesthesia was maintained with isoflurane (n = 7) or sevoflurane (n = 3) in oxygen-nitrous oxide. Controlled hypotension was induced by Ap4A administered at a rate of 10-20 micrograms.kg-1.min-1. The dose was adjusted at a maximum rate of 80 micrograms.kg-1.min-1 until the target blood pressure was achieved. Arterial blood pressure and heart rate were monitored. Arterial samples were drawn at 4 separate time points to measure the concentration of Ap4A in the plasma. The time required for attaining the target blood pressure after initiation of Ap4A infusion was about 16 min, and the time lapse between withdrawal of infusion to recovery of blood pressure was about 18 min. No reflex tachycardia was observed during infusion of Ap4A and no rebound hypertension was evident after withdrawal. The plasma Ap4A concentration increased in response to the acceleration rate of Ap4A administration with a tendency of augmented hypotensive effect. As it produces an excellent hypotensive effect together with a modulating action on blood pressure, Ap4A was assessed as useful in producing controlled hypotension.

Army and Marine Corps Active Protection System (APS) Efforts

DTIC Science & Technology

2016-08-30

safe enough for operational use, the benefits of MAPS relative to non-developmental efforts, MAPS’ impacts on NDI APS performance and costs, the Army’s...APSs Effective and Safe Enough for Operational Use? .............................. 24 What are the Benefits of MAPS Relative to Non-Developmental...corrosion—which will also factor into their eventual APS plans. Potential issues for Congress include whether current NDI APSs are effective and

Electrical properties and transport mechanisms in phase change memory thin films of quasi-binary-line GeTe–Sb{sub 2}Te{sub 3} chalcogenide semiconductors

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

Sherchenkov, A. A.; Kozyukhin, S. A., E-mail: sergkoz@igic.ras.ru; Lazarenko, P. I.

The temperature dependences of the resistivity and current–voltage (I–V) characteristics of phase change memory thin films based on quasi-binary-line GeTe–Sb{sub 2}Te{sub 3} chalcogenide semiconductors Ge{sub 2}Sb{sub 2}Te{sub 5}, GeSb{sub 2}Te{sub 5}, and GeSb{sub 4}Te{sub 7} are investigated. The effect of composition variation along the quasibinary line on the electrical properties and transport mechanisms of the thin films is studied. The existence of three ranges with different I–V characteristics is established. The position and concentration of energy levels controlling carrier transport are estimated. The results obtained show that the electrical properties of the thin films can significantly change during a shiftmore » along the quasi-binary line GeTe–Sb{sub 2}Te{sub 3}, which is important for targeted optimization of the phase change memory technology.« less

Health in All Policies (HiAP) governance: lessons from network governance.

PubMed

Khayatzadeh-Mahani, Akram; Ruckert, Arne; Labonté, Ronald; Kenis, Patrick; Akbari-Javar, Mohammad Reza

2018-05-25

The Health in All Policies (HiAP) approach requires formal and sustained governance structures and mechanisms to ensure that the policies of various non-health sectors maximize positive and minimize negative impacts on population health. In this paper, we demonstrate the usefulness of a network perspective in understanding and contributing to the effectiveness of HiAP. We undertook an exploratory, qualitative case study of a HiAP structure in Iran, the Kerman province Council of Health and Food Security (CHFS) with diverse members from health and non-health sectors. We analyzed relevant policy texts and interviewed 32 policy actors involved in the CHFS. Data were analyzed using within-case analysis and constant comparative methodology. Our findings suggest that CHFS governance from a network perspective drew in practice on elements of two competing network governance modes: the network administrative organization (NAO) and the lead organization mode. Our results also show that a shift from a hierarchical and market-based mode of interaction to a network logic within CHFS has not yet taken place. In addition, CHFS suffers from large membership and an inability to address complex 'wicked problems', as well as low trust, legitimacy and goal consensus among its members. Drawing on other HiAP studies and commentaries, insights from organization network theory, and in-depth findings from our case study, we conclude that a NAO may be the most effective mode of governance for tackling complex social problems in HiAP structures. Since similar studies are limited, and our single case study may not be transferable across all contexts, we suggest that further research be undertaken to explore HiAP structures from a network perspective in different institutional and cultural settings. With increasing emphasis given to HiAP approaches in national and international health policy discourse, it is important that comparative knowledge about the effectiveness of HiAP governance

Pentoxifylline Treatment in Acute Pancreatitis (AP)

ClinicalTrials.gov

2018-02-21

Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

Space-charge compensation measurements in electron cyclotron resonance ion source low energy beam transport lines with a retarding field analyzer

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

Winklehner, D.; Leitner, D., E-mail: leitnerd@nscl.msu.edu; Cole, D.

2014-02-15

In this paper we describe the first systematic measurement of beam neutralization (space charge compensation) in the ECR low energy transport line with a retarding field analyzer, which can be used to measure the potential of the beam. Expected trends for the space charge compensation levels such as increase with residual gas pressure, beam current, and beam density could be observed. However, the overall levels of neutralization are consistently low (<60%). The results and the processes involved for neutralizing ion beams are discussed for conditions typical for ECR injector beam lines. The results are compared to a simple theoretical beammore » plasma model as well as simulations.« less

The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters.

PubMed

Rigalli, Juan Pablo; Tocchetti, Guillermo Nicolás; Arana, Maite Rocío; Villanueva, Silvina Stella Maris; Catania, Viviana Alicia; Theile, Dirk; Ruiz, María Laura; Weiss, Johanna

2016-06-28

Breast cancer is the most frequent malignancy in women. Multidrug resistance due to overexpression of ABC drug transporters is a common cause of chemotherapy failure and disease recurrence. Genistein (GNT) is a phytoestrogen present in soybeans and hormone supplements. We investigated the effect of GNT on the expression and function of ABC transporters in MCF-7 and MDA-MB-231 breast cancer cell lines. Results demonstrated an induction at the protein level of ABCC1 and ABCG2 and of ABCC1 in MCF-7 and MDA-MB-231, respectively. MCF-7 cells showed a concomitant increase in doxorubicin and mitoxantrone efflux and resistance, dependent on ABCG2 activity. ABCC1 induction by GNT in MDA-MB-231 cells modified neither drug efflux nor chemoresistance due to simultaneous acute inhibition of the transporter activity by GNT. All inductions took place at the translational level, as no increment in mRNA was observed and protein increase was prevented by cycloheximide. miR-181a, already demonstrated to inhibit ABCG2 translation, was down-regulated by GNT, explaining translational induction. Effects were independent of classical estrogen receptors. Results suggest potential nutrient-drug interactions that could threaten chemotherapy efficacy, especially in ABCG2-expressing tumors treated with substrates of this transporter. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A New Photometric Study of Ap and Am Stars in the Infrared

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

Chen, P. S.; Liu, J. Y.; Shan, H. G., E-mail: chenps@ynao.ac.cn

In this paper, 426 well known confirmed Ap and Am stars are photometrically studied in the infrared. The 2MASS, Wide-field Infrared Survey Explorer ( WISE ), and IRAS data are employed to make analyses. The results in this paper have shown that in the 1–3 μ m region over 90% Ap and Am stars have no or little infrared excesses, and infrared radiations in the near-infrared from these stars are probably dominated by the free–free emissions. It is also shown that in the 3–12 μ m region, the majority of Ap stars and Am stars have very similar behavior, i.e.,more » in the W 1– W 2 (3.4–4.6 μ m) region, over half of Ap and Am stars have clear infrared excesses, which are possibly due to the binarity, the multiplicity, and/or the debris disk, but in the W 2– W 3 (4.6–12 μ m) region they have no or little infrared excess. In addition, in the 12–22 μ m region, some of Ap stars and Am stars show the infrared excesses and infrared radiations for these Ap and Am stars are probably due to the free–free emissions. In addition, it is seen that the probability of being the binarity, the multiplicity and/or the debris disk for Am stars is much higher than that for Ap stars. Furthermore, it can be seen that, in general, no relations can be found between infrared colors and spectral types either for Ap stars or for Am stars.« less

Renal Atp6ap2/(Pro)renin Receptor Is Required for Normal Vacuolar H+-ATPase Function but Not for the Renin-Angiotensin System.

PubMed

Trepiccione, Francesco; Gerber, Simon D; Grahammer, Florian; López-Cayuqueo, Karen I; Baudrie, Véronique; Păunescu, Teodor G; Capen, Diane E; Picard, Nicolas; Alexander, R Todd; Huber, Tobias B; Chambrey, Regine; Brown, Dennis; Houillier, Pascal; Eladari, Dominique; Simons, Matias

2016-11-01

ATPase H + -transporting lysosomal accessory protein 2 (Atp6ap2), also known as the (pro)renin receptor, is a type 1 transmembrane protein and an accessory subunit of the vacuolar H + -ATPase (V-ATPase) that may also function within the renin-angiotensin system. However, the contribution of Atp6ap2 to renin-angiotensin-dependent functions remains unconfirmed. Using mice with an inducible conditional deletion of Atp6ap2 in mouse renal epithelial cells, we found that decreased V-ATPase expression and activity in the intercalated cells of the collecting duct impaired acid-base regulation by the kidney. In addition, these mice suffered from marked polyuria resistant to desmopressin administration. Immunoblotting revealed downregulation of the medullary Na + -K + -2Cl - cotransporter NKCC2 in these mice compared with wild-type mice, an effect accompanied by a hypotonic medullary interstitium and impaired countercurrent multiplication. This phenotype correlated with strong autophagic defects in epithelial cells of medullary tubules. Notably, cells with high accumulation of the autophagosomal substrate p62 displayed the strongest reduction of NKCC2 expression. Finally, nephron-specific Atp6ap2 depletion did not affect angiotensin II production, angiotensin II-dependent BP regulation, or sodium handling in the kidney. Taken together, our results show that nephron-specific deletion of Atp6ap2 does not affect the renin-angiotensin system but causes a combination of renal concentration defects and distal renal tubular acidosis as a result of impaired V-ATPase activity. Copyright © 2016 by the American Society of Nephrology.

AE8/AP8 Implementations in AE9/AP9, IRBEM, and SPENVIS

DTIC Science & Technology

2014-02-18

period applies to orbit generation only; AE8/AP8 utilizes geomagnetic field models from other epochs as specified in the table below.) SHIELDOSE2 model...finite and semi- infinite slab data tables for Bremsstrahlung have been reversed [Heynderickx, private communication, May 2013]. This correction is...Cain, J. C., S. J. Hendricks, R. A. Langel, and W. V. Hudson (1967), A proposed model for the international geomagnetic reference field, 1965, J

Functional Analysis of AP-2 α and μ2 Subunits

PubMed Central

Motley, Alison M.; Berg, Nicola; Taylor, Marcus J.; Sahlender, Daniela A.; Hirst, Jennifer; Owen, David J.

2006-01-01

The AP-2 adaptor complex plays a key role in cargo recognition and clathrin-coated vesicle formation at the plasma membrane. To investigate the functions of individual binding sites and domains of the AP-2 complex in vivo, we have stably transfected HeLa cells with wild-type and mutant small interfering RNA–resistant α and μ2 subunits and then used siRNA knockdowns to deplete the endogenous proteins. Mutating the PtdIns(4,5)P2 binding site of α, the phosphorylation site of μ2, or the YXXΦ binding site of μ2 impairs AP-2 function, as assayed by transferrin uptake. In contrast, removing the C-terminal appendage domain of α, or mutating the PtdIns(4,5)P2 binding site of μ2, has no apparent effect. However, adding a C-terminal GFP tag to α renders it completely nonfunctional. These findings demonstrate that there is some functional redundancy in the binding sites of the various AP-2 subunits, because no single mutation totally abolishes function. They also help to explain why GFP-tagged AP-2 never appears to leave the plasma membrane in some live cell imaging studies. Finally, they establish a new model system that can be used both for additional structure-function analyses, and as a way of testing tagged constructs for function in vivo. PMID:17035630

A spatial analysis of the dispersion of transportation induced carbon monoxide using the Gaussian line source method

NASA Astrophysics Data System (ADS)

Tarigan, A. P. M.; Suryati, I.; Gusrianti, D.

2018-03-01

The Purpose of this study is to model the spatial distribution of transportation induced carbon monoxide (CO) from a street, i.e. Jl. Singamangaraja, in Medan City using the gaussian line source method with GIS. It is observed that the traffic volume on the Jl. Singamangaraja is 7,591 units/hour in the morning and 7,433 units/hour in the afternoon. The amount emission rate is 49,171.7 µg/m.s in the morning and 46,943.1 µg/m.s in the afternoon. Based on the gaussian line source method, the highest CO concentration is found at the roadside, i.e. 20,340 µg/Nm3 in the morning and 18,340 µg/Nm3 in the afternoon, which are fairly in agreement with those measured in situ. Using GIS, the CO spatial distribution can visually be modeled to observe the affected area.

Army and Marine Corps Active Protection System (APS) Efforts

DTIC Science & Technology

2016-08-23

with hard or soft kill capabilities to a variety of threats, including rocket -propelled grenades (RPGs) and anti-tank guided missiles (ATGMs). APS...of threats, including rocket -propelled grenades (RPGs) and anti-tank guided missiles (ATGMs). APS technologies are not new, and a number of nations...training. 1 RPGs are basically single man-portable, shoulder-fired, unguided rockets . RPGs have been widely proliferated but can be mitigated to a

ION EFFECTS IN THE APS PARTICLE ACCUMULATOR RING

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

Calvey, J.; Harkay, K.; Yao, CY.

2017-06-25

Trapped ions in the APS Particle Accumulator Ring (PAR) lead to a positive coherent tune shift in both planes, which increases along the PAR cycle as more ions accumulate. This effect has been studied using an ion simulation code developed at SLAC. After modifying the code to include a realistic vacuum profile, multiple ionization, and the effect of shaking the beam to measure the tune, the simulation agrees well with our measurements. This code has also been used to evaluate the possibility of ion instabilities at the high bunch charge needed for the APS-Upgrade.

Coaching in the AP Classroom

ERIC Educational Resources Information Center

Fornaciari, Jim

2013-01-01

Many parallels exist between quality coaches and quality classroom teachers--especially AP teachers, who often feel the pressure to produce positive test results. Having developed a series of techniques and strategies for building a team-oriented winning culture on the field, Jim Fornaciari writes about how he adapted those methods to work in the…

Line scanning time-of-flight laser sensor for intelligent transport systems, combining wide field-of-view optics of 30 deg, high scanning speed of 0.9 ms/line, and simple sensor configuration

NASA Astrophysics Data System (ADS)

Imaki, Masaharu; Kameyama, Shumpei; Ishimura, Eitaro; Nakaji, Masaharu; Yoshinaga, Hideo; Hirano, Yoshihito

2017-03-01

We developed a line scanning time-of-flight (TOF) laser sensor for an intelligent transport system (ITS), which combines wide field-of-view (FOV) receiving optics of 30 deg and a high-speed microelectro mechanical system scanner of 0.9 ms/line with a simple sensor configuration. The newly developed high-aspect ratio photodiode realizes the scanless and wide FOV receiver. The sinusoidal wave intensity modulation method is used for the TOF measurement. This enables the noise reduction of the trans-impedance amplifier by applying the LC-resonant method. The vehicle detection and axle counting, which are the important functions in ITS, are also demonstrated.

Molecular dynamics simulations of AP/HMX composite with a modified force field.

PubMed

Zhu, Wei; Wang, Xijun; Xiao, Jijun; Zhu, Weihua; Sun, Huai; Xiao, Heming

2009-08-15

An all-atom force field for ammonium perchlorate (AP) is developed with the framework of pcff force field. The structural parameters of AP obtained with the modified force field are in good agreement with experimental values. Molecular dynamics (MD) simulations have been performed to investigate AP/HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazocane) composite at different temperatures. The binding energies, thermal expansion coefficient, and the trigger bond lengths of HMX in the AP/HMX composite have been obtained. The binding energies of the system increase slightly with temperature increasing, peak at 245K, and then gradually decrease. The volume thermal expansion coefficient of the AP/HMX composite has been derived from the volume variation with temperature. As the temperature rises, the maximal lengths of the trigger bond N-NO(2) of HMX increase gradually. The simulated results indicate that the maximal length of trigger bond can be used as a criterion for judging the sensitivity of energetic composite.

Simulation and measurement of the electrostatic beam kicker in the low-energy undulator test line.

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

Waldschmidt, G. J.

1998-10-27

An electrostatic kicker has been constructed for use in the Low-Energy Undulator Test Line (LEUTL) at the Advanced Photon Source (APS). The function of the kicker is to limit the amount of beam current to be accelerated by the APS linac. Two electrodes within the kicker create an electric field that adjusts the trajectory of the beam. This paper will explore the static fields that are set up between the offset electrode plates and determine the reaction of the beam to this field. The kicker was numerically simulated using the electromagnetic solver package MAFIA [1].

Ten Things to Consider When Teaching AP U.S. History

ERIC Educational Resources Information Center

Libresco, Andrea S.

2013-01-01

This article describes 10 recommendations for creativity, higher-order thinking, and meaningful learning activities that can be used to guide teachers in constructing an engaging AP course: (1) Be on the committee that decides how students will be selected for AP; (2) Maximize time and connections through blocks of time with an English colleague;…

APS Goes to ComicCon and Other Tales: Reaching out for Physics

NASA Astrophysics Data System (ADS)

Kirby, Kate

2012-10-01

Broadly interpreting the core mission of APS ``to advance and diffuse the knowledge of physics", APS carries out programmatic activities in Education, Outreach, International Affairs, Public Affairs, and Advocacy, which benefit the physics community as well as society at large. These programs are highly valued by APS members who know about them, but the challenge has been to find ways to effectively communicate to our members about all the good things we are doing. APS programs have also achieved significant recognition in the external community for their outstanding quality and success. I will describe several examples of how we ``reach out" to promote physics and physics education in a variety of venues.

AP Geography, Environmental Science Thrive

ERIC Educational Resources Information Center

Robelen, Erik W.

2012-01-01

Geography may not be particularly known as a hot topic among today's students--even some advocates suggest it suffers from an image problem--but by at least one measure, the subject is starting to come into its own. Across more than 30 topics covered in the Advanced Placement (AP) program, participation in geography is rising faster than any…

Synthesis and binding properties of new selective ligands for the nucleobase opposite the AP site.

PubMed

Abe, Yukiko; Nakagawa, Osamu; Yamaguchi, Rie; Sasaki, Shigeki

2012-06-01

DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3'-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; that is A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site. Copyright © 2012 Elsevier Ltd. All rights reserved.

The adipocyte fatty acid–binding protein aP2 is required in allergic airway inflammation

PubMed Central

Shum, Bennett O.V.; Mackay, Charles R.; Gorgun, Cem Z.; Frost, Melinda J.; Kumar, Rakesh K.; Hotamisligil, Gökhan S.; Rolph, Michael S.

2006-01-01

The adipocyte fatty acid–binding protein aP2 regulates systemic glucose and lipid metabolism. We report that aP2, in addition to being abundantly expressed by adipocytes, is also expressed by human airway epithelial cells and shows a striking upregulation following stimulation of epithelial cells with the Th2 cytokines IL-4 and IL-13. Regulation of aP2 mRNA expression by Th2 cytokines was highly dependent on STAT6, a transcription factor with a major regulatory role in allergic inflammation. We examined aP2-deficient mice in a model of allergic airway inflammation and found that infiltration of leukocytes, especially eosinophils, into the airways was highly dependent on aP2 function. T cell priming was unaffected by aP2 deficiency, suggesting that aP2 was acting locally within the lung, and analysis of bone marrow chimeras implicated non-hematopoietic cells, most likely bronchial epithelial cells, as the site of action of aP2 in allergic airway inflammation. Thus, aP2 regulates allergic airway inflammation and may provide a link between fatty acid metabolism and asthma. PMID:16841093

49 CFR 192.179 - Transmission line valves.

Code of Federal Regulations, 2010 CFR

2010-10-01

... BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Design of Pipeline Components § 192.179 Transmission line valves. (a) Each transmission line, other than offshore segments, must have sectionalizing block... 49 Transportation 3 2010-10-01 2010-10-01 false Transmission line valves. 192.179 Section 192.179...

49 CFR 192.179 - Transmission line valves.

Code of Federal Regulations, 2013 CFR

2013-10-01

... BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Design of Pipeline Components § 192.179 Transmission line valves. (a) Each transmission line, other than offshore segments, must have sectionalizing block... 49 Transportation 3 2013-10-01 2013-10-01 false Transmission line valves. 192.179 Section 192.179...

49 CFR 192.179 - Transmission line valves.

Code of Federal Regulations, 2011 CFR

2011-10-01

... BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Design of Pipeline Components § 192.179 Transmission line valves. (a) Each transmission line, other than offshore segments, must have sectionalizing block... 49 Transportation 3 2011-10-01 2011-10-01 false Transmission line valves. 192.179 Section 192.179...

49 CFR 192.179 - Transmission line valves.

Code of Federal Regulations, 2014 CFR

2014-10-01

... BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Design of Pipeline Components § 192.179 Transmission line valves. (a) Each transmission line, other than offshore segments, must have sectionalizing block... 49 Transportation 3 2014-10-01 2014-10-01 false Transmission line valves. 192.179 Section 192.179...

49 CFR 192.179 - Transmission line valves.

Code of Federal Regulations, 2012 CFR

2012-10-01

... BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Design of Pipeline Components § 192.179 Transmission line valves. (a) Each transmission line, other than offshore segments, must have sectionalizing block... 49 Transportation 3 2012-10-01 2012-10-01 false Transmission line valves. 192.179 Section 192.179...

SARS coronavirus protein 7a interacts with human Ap4A-hydrolase.

PubMed

Vasilenko, Natalia; Moshynskyy, Igor; Zakhartchouk, Alexander

2010-02-09

The SARS coronavirus (SARS-CoV) open reading frame 7a (ORF 7a) encodes a 122 amino acid accessory protein. It has no significant sequence homology with any other known proteins. The 7a protein is present in the virus particle and has been shown to interact with several host proteins; thereby implicating it as being involved in several pathogenic processes including apoptosis, inhibition of cellular protein synthesis, and activation of p38 mitogen activated protein kinase. In this study we present data demonstrating that the SARS-CoV 7a protein interacts with human Ap4A-hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17). Ap4A-hydrolase is responsible for metabolizing the "allarmone" nucleotide Ap4A and therefore likely involved in regulation of cell proliferation, DNA replication, RNA processing, apoptosis and DNA repair. The interaction between 7a and Ap4A-hydrolase was identified using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation from cultured human cells transiently expressing V5-His tagged 7a and HA tagged Ap4A-hydrolase. Human tissue culture cells transiently expressing 7a and Ap4A-hydrolase tagged with EGFP and Ds-Red2 respectively show these proteins co-localize in the cytoplasm.

The 8th Annual AP[R] Report to the Nation

ERIC Educational Resources Information Center

College Board, 2012

2012-01-01

In classrooms around the country, AP (Advanced Placement) teachers are preparing students for tomorrow by teaching them how to think and learn today. AP students learn to construct solid arguments, test theories, and see many sides of an issue--the kind of thinking that solves tough problems both in and outside the classroom, in college and…

Expansion and stress responses of the AP2/EREBP superfamily in cotton.

PubMed

Liu, Chunxiao; Zhang, Tianzhen

2017-01-31

The allotetraploid cotton originated from one hybridization event between an extant progenitor of Gosssypium herbaceum (A 1 ) or G. arboreum (A 2 ) and another progenitor, G. raimondii Ulbrich (D 5 ) 1-1.5 million years ago (Mya). The APETALA2/ethylene-responsive element binding protein (AP2/EREBP) transcription factors constitute one of the largest and most conserved gene families in plants. They are characterized by their AP2 domain, which comprises 60-70 amino acids, and are classified into four main subfamilies: the APETALA2 (AP2), Related to ABI3/VP1 (RAV), Dehydration-Responsive Element Binding protein (DREB) and Ethylene-Responsive Factor (ERF) subfamilies. The AP2/EREBP genes play crucial roles in plant growth, development and biotic and abiotic stress responses. Hence, understanding the molecular characteristics of cotton stress tolerance and gene family expansion would undoubtedly facilitate cotton resistance breeding and evolution research. A total of 269 AP2/EREBP genes were identified in the G. raimondii (D5) cotton genome. The protein domain architecture and intron/exon structure are simple and relatively conserved within each subfamily. They are distributed throughout all chromosomes but are clustered on various chromosomes due to genomic tandem duplication. We identified 73 tandem duplicated genes and 221 segmental duplicated gene pairs which contributed to the expansion of AP2/EREBP superfamily. Of them, tandem duplication was the most important force of the expansion of the B3 group. Transcriptome analysis showed that 504 AP2/EREBP genes were expressed in at least one tested G. hirsutum TM-1 tissues. In G. hirsutum, 151 non-repeated genes of the DREB and ERF subfamily genes were responsive to different stresses: 132 genes were induced by cold, 63 genes by drought and 94 genes by heat. qRT-PCR confirmed that 13 GhDREB and 15 GhERF genes were induced by cold and/or drought. No transcripts detected for 53 of the 111 tandem duplicated genes in TM-1

Amphioxus and lamprey AP-2 genes: implications for neural crest evolution and migration patterns

NASA Technical Reports Server (NTRS)

Meulemans, Daniel; Bronner-Fraser, Marianne

2002-01-01

The neural crest is a uniquely vertebrate cell type present in the most basal vertebrates, but not in cephalochordates. We have studied differences in regulation of the neural crest marker AP-2 across two evolutionary transitions: invertebrate to vertebrate, and agnathan to gnathostome. Isolation and comparison of amphioxus, lamprey and axolotl AP-2 reveals its extensive expansion in the vertebrate dorsal neural tube and pharyngeal arches, implying co-option of AP-2 genes by neural crest cells early in vertebrate evolution. Expression in non-neural ectoderm is a conserved feature in amphioxus and vertebrates, suggesting an ancient role for AP-2 genes in this tissue. There is also common expression in subsets of ventrolateral neurons in the anterior neural tube, consistent with a primitive role in brain development. Comparison of AP-2 expression in axolotl and lamprey suggests an elaboration of cranial neural crest patterning in gnathostomes. However, migration of AP-2-expressing neural crest cells medial to the pharyngeal arch mesoderm appears to be a primitive feature retained in all vertebrates. Because AP-2 has essential roles in cranial neural crest differentiation and proliferation, the co-option of AP-2 by neural crest cells in the vertebrate lineage was a potentially crucial event in vertebrate evolution.

High intensity proton beam transportation through fringe field of 70 MeV compact cyclotron to beam line targets

NASA Astrophysics Data System (ADS)

Zhang, Xu; Li, Ming; Wei, Sumin; Xing, Jiansheng; Hu, Yueming; Johnson, Richard R.; Piazza, Leandro; Ryjkov, Vladimir

2016-06-01

From the stripping points, the high intensity proton beam of a compact cyclotron travels through the fringe field area of the machine to the combination magnet. Starting from there the beams with various energy is transferred to the switching magnet for distribution to the beam line targets. In the design of the extraction and transport system for the compact proton cyclotron facilities, such as the 70 MeV in France and the 100 MeV in China, the space charge effect as the beam crosses the fringe field has not been previously considered; neither has the impact on transverse beam envelope coupled from the longitudinal direction. Those have been concerned much more with the higher beam-power because of the beam loss problem. In this paper, based on the mapping data of 70 MeV cyclotron including the fringe field by BEST Cyclotron Inc (BEST) and combination magnet field by China Institute of Atomic Energy (CIAE), the beam extraction and transport are investigated for the 70 MeV cyclotron used on the SPES project at Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali di Legnaro (INFN-LNL). The study includes the space charge effect and longitudinal and transverse coupling mentioned above, as well as the matching of beam optics using the beam line for medical isotope production as an example. In addition, the designs of the ±45° switching magnets and the 60° bending magnet for the extracted beam with the energy from 35 MeV to 70 MeV have been made. Parts of the construction and field measurements of those magnets have been done as well. The current result shows that, the design considers the complexity of the compact cyclotron extraction area and fits the requirements of the extraction and transport for high intensity proton beam, especially at mA intensity levels.

Michigan transportation facts & figures : highways

DOT National Transportation Integrated Search

2002-08-16

This on-line document is part of a series, Transportation Facts & Figures, by the Michigan Department of Transportation (MDOT). The Highways section of Transportation Facts & Figures cover such topics as population changes, vehicle registrations, fue...

A new medium energy beam transport line for the proton injector of AGS-RHIC

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

Okamura, M.; Briscoe, B.; Fite, J.

2010-09-12

In Brookhaven National Laboratory (BNL), a 750 keV medium energy beam transport line between the 201 MHz 750 keV proton RFQ and the 200 MeV Alvarez DTL is being modified to get a better transmission of the beam. Within a tight space, high field gradient quadrupoles (65 Tm) and newly designed steering magnets (6.5 mm in length) will be installed considering the cross-talk effects. Also a new half wave length 200 MHz buncher is being prepared. The beam commissioning will be done in this year. To enhance the performance of the proton linacs, the MEBT is being modified. New quadrupolemore » magnets, steering magnets and a half wave length buncher as shown in Figure 7 will be installed and be commissioned soon.« less

A role for gamma-glutamyl transpeptidase and the amino acid transport system xc- in cystine transport by a human pancreatic duct cell line.

PubMed Central

Sweiry, J H; Sastre, J; Viña, J; Elsässer, H P; Mann, G E

1995-01-01

1. The roles of the gamma-glutamyl cycle and the anionic amino acid transport system xc- in mediating L-cystine uptake were investigated in cultured human pancreatic duct PaTu 8902 cells. This cell line exhibits morphological features of normal pancreatic duct cells and expresses gamma-glutamyl transpeptidase (gamma-GT, EC 2.3.2.2), an enzyme involved in the metabolism and regulation of intracellular glutathione (GSH). 2. Uptake of L-cystine (10 microM) was linear for up to 10 min, temperature dependent, Na+ independent, saturable (Michaelis-Menten constant (Km), 86 +/- 25 microM; maximal velocity (Vmax), 109 +/- 33 nmol (mg protein)-1 h-1) and reduced by 80-90% by a 50-fold excess concentration of L-glutamate and L-homocysteic acid, but not L-aspartate. These transport properties resemble those described for system xc-, which exchanges cystine for intracellular glutamate. 3. Acivicin, a known inhibitor of gamma-GT, decreased gamma-GT activity from 2.58 +/- 0.96 to 0.97 +/- 0.11 mU (mg protein)-1 and decreased the initial rates of L-cystine and L-glutamine uptake by 41-55%. Anthglutin (1-gamma-L-glutamyl-2-(2-carboxyphenylhyl)hydrazine), a structurally different inhibitor of gamma-GT, also caused a concentration-dependent (0.01-1 mM) decrease in gamma-GT activity and L-cystine uptake. 4. Neither acivicin nor anthglutin inhibited the uptake of L-glutamate, a poor substrate for gamma-GT. 5. In the presence of a 500-fold excess concentration of glutamate, which should abolish entry of cystine via system xc-, the remaining fraction of cystine transport was inhibited by 50% by acivicin, suggesting that transport is, in part, dependent on the activity of gamma-GT. 6. Cystine transport was also 60-80% inhibited by a series of gamma-glutamyl amino acids (5 mM) including gamma-glutamyl-glutamate, gamma-glutamyl-glutamine and gamma-glutamyl-glycine. alpha-Dipeptides inhibited cystine transport by only 6-22%. 7. These findings demonstrate that in human pancreatic duct Pa

Molecular characterization and specific detection of Anaplasma species (AP-sd) in sika deer and its first detection in wild brown bears and rodents in Hokkaido, Japan.

PubMed

Moustafa, Mohamed Abdallah Mohamed; Lee, Kyunglee; Taylor, Kyle; Nakao, Ryo; Sashika, Mariko; Shimozuru, Michito; Tsubota, Toshio

2015-12-01

A previously undescribed Anaplasma species (herein referred to as AP-sd) has been detected in sika deer, cattle and ticks in Japan. Despite being highly similar to some strains of A. phagocytophilum, AP-sd has never been detected in humans. Its ambiguous epidemiology and the lack of tools for its specific detection make it difficult to understand and interpret the prevalence of this Anaplasma species. We developed a method for specific detection, and examined AP-sd prevalence in Hokkaido wildlife. Our study included 250 sika deer (Cervus nippon yesoensis), 13 brown bears (Ursus arctos yesoensis) and 252 rodents including 138 (Apodemus speciosus), 45 (Apodemus argenteus), 42 (Myodes rufocanus) and 27 (Myodes rutilus) were collected from Hokkaido island, northern Japan, collected during 2010 to 2015. A 770 bp and 382 bp segment of the 16S rRNA and gltA genes, respectively, were amplified by nested PCR. Results were confirmed by cloning and sequencing of the positive PCR products. A reverse line blot hybridization (RLB) based on the 16S rRNA gene was then developed for the specific detection of AP-sd. The prevalence of AP-sd by nested PCR in sika deer was 51% (128/250). We detected this Anaplasma sp. for the first time in wild brown bears and rodents with a prevalence of 15% (2/13) and 2.4% (6/252), respectively. The sequencing results of the 16S rRNA and gltA gene amplicons were divergent from the selected A. phagocytophilum sequences in GenBank. Using a newly designed AP-sd specific probe for RLB has enabled us to specifically detect this Anaplasma species. Besides sika deer and cattle, wild brown bears and rodents were identified as potential reservoir hosts for AP-sd. This study provided a high throughput molecular method that specifically detects AP-sd, and which can be used to investigate its ecology and its potential as a threat to humans in Japan. Copyright © 2015 Elsevier B.V. All rights reserved.

The H2 receptor antagonist nizatidine is a P-glycoprotein substrate: characterization of its intestinal epithelial cell efflux transport.

PubMed

Dahan, Arik; Sabit, Hairat; Amidon, Gordon L

2009-06-01

The aim of this study was to elucidate the intestinal epithelial cell efflux transport processes that are involved in the intestinal transport of the H(2) receptor antagonist nizatidine. The intestinal epithelial efflux transport mechanisms of nizatidine were investigated and characterized across Caco-2 cell monolayers, in the concentration range 0.05-10 mM in both apical-basolateral (AP-BL) and BL-AP directions, and the transport constants of P-glycoprotein (P-gp) efflux activity were calculated. The concentration-dependent effects of various P-gp (verapamil, quinidine, erythromycin, ketoconazole, and cyclosporine A), multidrug resistant-associated protein 2 (MRP2; MK-571, probenecid, indomethacin, and p-aminohipuric acid), and breast cancer resistance protein (BCRP; Fumitremorgin C) inhibitors on nizatidine bidirectional transport were examined. Nizatidine exhibited 7.7-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. All P-gp inhibitors investigated displayed concentration-dependent inhibition on nizatidine secretion in both directions. The IC(50) of verapamil on nizatidine P-gp secretion was 1.2 x 10(-2) mM. In the absence of inhibitors, nizatidine displayed concentration-dependent secretion, with one saturable (J(max) = 5.7 x 10(-3) nmol cm(-2) s(-1) and K(m) = 2.2 mM) and one nonsaturable component (K(d) = 7 x 10(-4) microL cm(-2) s(-1)). Under complete P-gp inhibition, nizatidine exhibited linear secretory flux, with a slope similar to the nonsaturable component. V(max) and K(m) estimated for nizatidine P-gp-mediated secretion were 4 x 10(-3) nmol cm(-2) s(-1) and 1.2 mM, respectively. No effect was obtained with the MRP2 or the BCRP inhibitors. Being a drug commonly used in pediatrics, adults, and elderly, nizatidine susceptibility to efflux transport by P-gp revealed in this paper may be of significance in its absorption, distribution, and clearance, as well as possible drug-drug interactions.

CLEARING MAGNET DESIGN FOR APS-U

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

Abliz, M.; Grimmer, J.; Jaski, Y.

2017-06-25

The Advanced Photon Source is in the process of developing an upgrade (APS-U) of the storage ring. The upgrade will be converting the current double bend achromat (DBA) lattice to a multi-bend achromat (MBA) lattice. In addition, the storage ring will be operated at 6 GeV and 200 mA with regular swap-out injection to keep the stored beam current constant [1]. The swap-out injection will take place with beamline shutters open. For radiation safety to ensure that no electrons can exit the storage ring, a passive method of protecting the beamline and containing the electrons inside the storage ring ismore » proposed. A clearing magnet will be located in all beamline front ends inside the storage ring tunnel. This article will discuss the features and design of the clearing magnet scheme for APS-U.« less

Michigan transportation facts & figures : marine

DOT National Transportation Integrated Search

2002-08-17

This on-line document is part of a series, Transportation Facts & Figures, by the Michigan Department of Transportation (MDOT). The Marine section of Transportation Facts & Figures cover such topics as commercial ports, commodities carried, and ferry...

Effect of Different Angular Momentum Transport Mechanisms on the Radial Volatile Distribution in Protoplanetary Disks

NASA Astrophysics Data System (ADS)

Kalyaan, Anusha; Desch, Steven

2018-01-01

How circumstellar disks evolve and transport angular momentum is a mystery even until today. Magnetorotational instability (MRI; [1]) earlier thought to be a primary driver of disk evolution, has been found to be not as strong a candidate in cold insufficiently ionized protoplanetary disks where non-ideal MHD effects take over to efficiently suppress the instability [2][3]. In the past few years, recent studies have proposed different mechanisms such as magnetically-driven disk winds [4][5], convective overstability [6], and the vertical shear instability (VSI)[7] to be likely drivers of disk evolution. In this work, we consider numerically [8] and/or parametrically derived radial α profiles of three different mechanisms of angular momentum transport (hydrodynamic instabilities such as VSI, disk winds, and MRI) to understand how the underlying disk structure changes and evolves with each mechanism. We overlay our snowline model that incorporates the advection and diffusion of volatiles as well as radial drift of solids [9] to understand how different α profiles can affect the distribution of water in the disk. References: [1] Balbus, S.A., & Hawley, J.F.,1998, Rev. of Mod. Phys., 70, 1 [2] Bai, X.-N., & Stone, J.M. 2011, ApJ, 736, 144 [3] Bai, X.-N., & Stone, J.M., 2013, ApJ, 769, 76 [4] Bai, X.-N., 2016, ApJ, 821, 80 [5] Suzuki, T.K., Ogihara, M., Morbidelli, A., Crida, A., & Guillot, T., 2016, A&A, 596, A74 [6] Klahr, H., & Hubbard, A. 2014, ApJ, 788, 21 [7] Stoll, M.H.R., & Kley, W. 2014, A&A, 572, A77 [8] Kalyaan, A., Desch, S.J., & Monga, N., 2015, ApJ, 815, 112 [9] Desch, S.J., Estrada, P.R., Kalyaan, A., & Cuzzi, J.N., 2017, ApJ, 840, 86

Metal line blanketing and opacity in the ultraviolet of alpha 2 Canum Venaticorum

NASA Technical Reports Server (NTRS)

Molnar, M. R.

1972-01-01

Ultraviolet photometry by OAO-2 was made of alpha 2 CVn covering the entire 5.5d period of this magnetic Ap variable. The light curves ranging from 1330 A to 3320 A indicate the dominant role of rare-earth line-blanketing in redistributing flux. In a broad depression of the continuum covering 2300-2600 A, scanner observations possibly identify strong lines of Eu III as major contributors to this feature. At maximum intensity of the rare-earth lines, the ultraviolet continuum shortward of 2900 A is greatly diminished while the longer wavelength regions into the visual become brighter. In addition, there is evidence that the hydrogen line opacity is variable and the photoionization edge of Si I at 1680 A is identified.

Performance evaluation of rotating pump jet mixing of radioactive wastes in Hanford Tanks 241-AP-102 and -104

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

Onishi, Y.; Recknagle, K.P.

The purpose of this study was to confirm the adequacy of a single mixer pump to fully mix the wastes that will be stored in Tanks 241-AP-102 and -104. These Hanford double-shell tanks (DSTs) will be used as staging tanks to receive low-activity wastes from other Hanford storage tanks and, in turn, will supply the wastes to private waste vitrification facilities for eventual solidification. The TEMPEST computer code was applied to Tanks AP-102 and -104 to simulate waste mixing generated by the 60-ft/s rotating jets and to determine the effectiveness of the single rotating pump to mix the waste. TEMPESTmore » simulates flow and mass/heat transport and chemical reactions (equilibrium and kinetic reactions) coupled together. Section 2 describes the pump jet mixing conditions the authors evaluated, the modeling cases, and their parameters. Section 3 reports model applications and assessment results. The summary and conclusions are presented in Section 4, and cited references are listed in Section 5.« less

THE AP-2 CLATHRIN ADAPTOR MEDIATES ENDOCYTOSIS OF AN INHIBITORY KILLER CELL Ig-LIKE RECEPTOR (KIR) IN HUMAN NK CELLS1

PubMed Central

Purdy, Amanda K.; Alvarez-Arias, Diana A.; Oshinsky, Jennifer; James, Ashley M.; Serebriiskii, Ilya; Campbell, Kerry S.

2014-01-01

Stable surface expression of human inhibitory killer cell immunoglobulin-like receptors (KIR) is critical for controlling NK cell function and maintaining NK cell tolerance toward normal MHC-I+ cells. Our recent experiments, however, have found that antibody-bound KIR3DL1 (3DL1) readily leaves the cell surface and undergoes endocytosis to early/recycling endosomes and subsequently to late endosomes. We found that 3DL1 internalization is at least partially mediated by an interaction between the μ2 subunit of the AP-2 clathrin adaptor complex and ITIM tyrosine residues in the cytoplasmic domain of 3DL1. Disruption of the 3DL1/μ2 interaction, either by mutation of the ITIM tyrosines in 3DL1 or mutation of μ2, significantly diminished endocytosis and increased surface expression of 3DL1 in human primary NK cells and cell lines. Furthermore, we found that the 3DL1/AP-2 interaction is diminished upon antibody engagement with the receptor, as compared to untreated cells. Thus, we have identified AP-2-mediated endocytosis as a mechanism regulating the surface levels of inhibitory KIR though their ITIM domains. Based upon our results, we propose a model in which non-engaged KIR are internalized by this mechanism, whereas engagement with MHC-I ligand would diminish AP-2 binding, thereby prolonging stable receptor surface expression and promoting inhibitory function. Furthermore, this ITIM-mediated mechanism may similarly regulate the surface expression of other inhibitory immune receptors. PMID:25238755

77 FR 67442 - Soo Line Railroad Company-Temporary Trackage Rights Exemption-BNSF Railway Company

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-09

... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. FD 35687] Soo Line Railroad Company--Temporary Trackage Rights Exemption-- BNSF Railway Company BNSF Railway Company (BNSF), pursuant... rights to Soo Line Railroad Company d/b/a Canadian Pacific (Soo Line) over BNSF's line of railroad...

Michigan transportation facts & figures : railroads

DOT National Transportation Integrated Search

2002-08-16

This on-line document is part of a series, Transportation Facts & Figures, by the Michigan Department of Transportation (MDOT). The Railroad section of Transportation Facts & Figures cover such topics as miles of track owned by companies in Michigan,...

[Cloning, subcellular localization, and heterologous expression of ApNAC1 gene from Andrographis paniculata].

PubMed

Wang, Jian; Qi, Meng-Die; Guo, Juan; Shen, Ye; Lin, Hui-Xin; Huang, Lu-Qi

2017-03-01

Andrographis paniculata is widely used as medicinal herb in China for a long time and andrographolide is its main medicinal constituent. To investigate the underlying andrographolide biosynthesis mechanisms, RNA-seq for A. paniculata leaves with MeJA treatment was performed. In A. paniculata transcriptomic data, the expression pattern of one member of NAC transcription factor family (ApNAC1) matched with andrographolide accumulation. The coding sequence of ApNAC1 was cloned by RT-PCR, and GenBank accession number was KY196416. The analysis of bioinformatics showed that the gene encodes a peptide of 323 amino acids, with a predicted relative molecular weight of 35.9 kDa and isoelectric point of 6.14. To confirm the subcellular localization, ApNAC1-GFP was transiently expressed in A. paniculata protoplast. The results indicated that ApNAC1 is a nucleus-localized protein. The analysis of real-time quantitative PCR revealed that ApNAC1 gene predominantly expresses in leaves. Compared with control sample, its expression abundance sharply increased with methyl jasmonate treatment. Based on its expression pattern, ApNAC1 gene might involve in andrographolide biosynthesis. ApNAC1 was heterologously expressed in Escherichia coli and recombinant protein was purified by Ni-NTA agarose. Further study will help us to understand the function of ApNAC1 in andrographolide biosynthesis. Copyright© by the Chinese Pharmaceutical Association.

IKKα contributes to UVB-induced VEGF expression by regulating AP-1 transactivation

PubMed Central

Dong, Wen; Li, Yi; Gao, Ming; Hu, Meiru; Li, Xiaoguang; Mai, Sanyue; Guo, Ning; Yuan, Shengtao; Song, Lun

2012-01-01

Exposure to ultraviolet B (UVB) irradiation from sunlight induces the upregulation of VEGF, a potent angiogenic factor that is critical for mediating angiogenesis-associated photodamage. However, the molecular mechanisms related to UVB-induced VEGF expression have not been fully defined. Here, we demonstrate that one of the catalytic subunits of the IκB kinase complex (IKK), IKKα, plays a critical role in mediating UVB-induced VEGF expression in mouse embryonic fibroblasts (MEFs), which requires IKKα kinase activity but is independent of IKKβ, IKKγ and the transactivation of NF-κB. We further show that the transcriptional factor AP-1 functions as the downstream target of IKKα that is responsible for VEGF induction under UVB exposure. Both the accumulation of AP-1 component, c-Fos and the transactivation of AP-1 by UVB require the activated IKKα located within the nucleus. Moreover, nuclear IKKα can associate with c-Fos and recruit to the vegf promoter regions containing AP-1-responsive element and then trigger phosphorylation of the promoter-bound histone H3. Thus, our results have revealed a novel independent role for IKKα in controlling VEGF expression during the cellular UVB response by regulating the induction of the AP-1 component and phosphorylating histone H3 to facilitate AP-1 transactivation. Targeting IKKα shows promise for the prevention of UVB-induced angiogenesis and the associated photodamage. PMID:22169952

Magnetic Measurements of Storage Ring Magnets for the APS Upgrade Project

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

Doose, C.; Dejus, R.; Jaski, M.

2017-06-01

Extensive prototyping of storage ring magnets is ongoing at the Advanced Photon Source (APS) in support of the APS Multi-Bend Achromat (MBA) upgrade project (APS-U) [1]. As part of the R&D activities four quadrupole magnets with slightly different geometries and pole tip materials, and one sextupole magnet with vanadium permendur (VP) pole tips were designed, built and tested. Magnets were measured individually using a rotating coil and a Hall probe for detailed mapping of the magnetic field. Magnets were then assembled and aligned relative to each other on a steel support plate and concrete plinth using precision machined surfaces tomore » gain experience with the alignment method chosen for the APS-U storage ring magnets. The required alignment of magnets on a common support structure is 30 μm rms. Measurements of magnetic field quality, strength and magnet alignment after subjecting the magnets and assemblies to different tests are presented.« less

Time, Concentration, and pH-Dependent Transport and Uptake of Anthocyanins in a Human Gastric Epithelial (NCI-N87) Cell Line.

PubMed

Atnip, Allison A; Sigurdson, Gregory T; Bomser, Joshua; Giusti, M Mónica

2017-02-18

Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87) has been used to study the behavior of anthocyanins at a pH range of 3.0-7.4. This work examines the effects of time (0-3 h), concentration (50-1500 µM), and pH (3.0, 5.0, 7.4) on the transport and uptake of anthocyanins using NCI-N87 cells. Anthocyanins were transported from the apical to basolateral side of NCI-N87 cells in time and dose dependent manners. Over the treatment time of 3 h the rate of transport increased, especially with higher anthocyanin concentrations. The non-linear rate of transport may suggest an active mechanism for the transport of anthocyanins across the NCI-N87 monolayer. At apical pH 3.0, higher anthocyanin transport was observed compared to pH 5.0 and 7.4. Reduced transport of anthocyanins was found to occur at apical pH 5.0.

Time, Concentration, and pH-Dependent Transport and Uptake of Anthocyanins in a Human Gastric Epithelial (NCI-N87) Cell Line

PubMed Central

Atnip, Allison A.; Sigurdson, Gregory T.; Bomser, Joshua; Giusti, M. Mónica

2017-01-01

Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87) has been used to study the behavior of anthocyanins at a pH range of 3.0–7.4. This work examines the effects of time (0–3 h), concentration (50–1500 µM), and pH (3.0, 5.0, 7.4) on the transport and uptake of anthocyanins using NCI-N87 cells. Anthocyanins were transported from the apical to basolateral side of NCI-N87 cells in time and dose dependent manners. Over the treatment time of 3 h the rate of transport increased, especially with higher anthocyanin concentrations. The non-linear rate of transport may suggest an active mechanism for the transport of anthocyanins across the NCI-N87 monolayer. At apical pH 3.0, higher anthocyanin transport was observed compared to pH 5.0 and 7.4. Reduced transport of anthocyanins was found to occur at apical pH 5.0. PMID:28218720

Beam transport program for FEL project

NASA Astrophysics Data System (ADS)

Sugimoto, Masayoshi; Takao, Masaru

1992-07-01

A beam transport program is developed to design the beam transport line of the free electron laser system at JAERI and to assist the beam diagnosis. The program traces a beam matrix through the elements in the beam transport line and the accelerators. The graphical user interface is employed to access the parameters and to represent the results. The basic computational method is based on the LANL-TRACE program and it is rewritten for personal computers in Pascal.

P alpha-chiral phosphorothioate analogues of bis(5'-adenosyl)tetraphosphate (Ap4A); their enzymatic synthesis and degradation.

PubMed Central

Lazewska, D; Guranowski, A

1990-01-01

Synthesis of Sp and Rp diastereomers of Ap4A alpha S has been characterized in two enzymatic systems, the lysyl-tRNA synthetase from Escherichia coli and the Ap4A alpha, beta-phosphorylase from Saccharomyces cerevisiae. The synthetase was able to use both (Sp)ATP alpha S and (Rp)ATP alpha S as acceptors of adenylate thus yielding corresponding monothioanalogues of Ap4A,(Sp) Ap4A alpha S and (Rp)Ap4A alpha S. No dithiophosphate analogue was formed. Relative synthetase velocities of the formation of Ap4A,(Sp) Ap4A alpha S and (Rp)Ap4A alpha S were 1:0.38:0.15, and the computed Km values for (Sp)ATP alpha S and (Rp)ATP alpha S were 0.48 and 1.34 mM, respectively. The yeast Ap4A phosphorylase synthesized (Sp)Ap4A alpha S and (Rp)Ap4A alpha S using adenosine 5'-phosphosulfate (APS) as source of adenylate. The adenylate was accepted by corresponding thioanalogues of ATP. In that system, relative velocities of Ap4A, (Sp)Ap4A alpha S and (Rp)Ap4A alpha S formation were 1:0.15:0.60. The two isomeric phosphorothioate analogues of Ap4A were tested as substrates for the following specific Ap4A-degrading enzymes: (asymmetrical) Ap4A hydrolase (EC 3.6.1.17) from yellow lupin (Lupinus luteus) seeds hydrolyzed each of the analogues to AMP and the corresponding isomer of ATP alpha S; (symmetrical) Ap4A hydrolase (EC 3.6.1.41) from E. coli produced ADP and the corresponding diastereomer of ADP alpha S; and Ap4A phosphorylase (EC 2.7.7.53) from S. cerevisiae cleaved the Rp isomer only at the unmodified end yielding ADP and (Rp)ATP alpha S whereas the Sp isomer was degraded non-specifically yielding a mixture of ADP, (Sp)ADP alpha S, ATP and (Sp)ATP alpha S. For all the Ap4A-degrading enzymes, the Rp isomer of Ap4A alpha S appeared to be a better substrate than its Sp counterpart; stereoselectivity of the three enzymes for the Ap4A alpha S diastereomers is 51, 6 and 2.5, respectively. Basic kinetic parameters of the degradation reactions are presented and structural requirements of

49 CFR 192.375 - Service lines: Plastic.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Service lines: Plastic. 192.375 Section 192.375... § 192.375 Service lines: Plastic. (a) Each plastic service line outside a building must be installed... terminate above ground level and outside the building, if— (i) The above ground level part of the plastic...

49 CFR 192.375 - Service lines: Plastic.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Service lines: Plastic. 192.375 Section 192.375... § 192.375 Service lines: Plastic. (a) Each plastic service line outside a building must be installed... terminate above ground level and outside the building, if— (i) The above ground level part of the plastic...

49 CFR 192.375 - Service lines: Plastic.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Service lines: Plastic. 192.375 Section 192.375... § 192.375 Service lines: Plastic. (a) Each plastic service line outside a building must be installed... terminate above ground level and outside the building, if— (i) The above ground level part of the plastic...

49 CFR 192.375 - Service lines: Plastic.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Service lines: Plastic. 192.375 Section 192.375... § 192.375 Service lines: Plastic. (a) Each plastic service line outside a building must be installed... terminate above ground level and outside the building, if— (i) The above ground level part of the plastic...

49 CFR 192.375 - Service lines: Plastic.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Service lines: Plastic. 192.375 Section 192.375... § 192.375 Service lines: Plastic. (a) Each plastic service line outside a building must be installed... terminate above ground level and outside the building, if— (i) The above ground level part of the plastic...

Hibernoma formation in transgenic mice and isolation of a brown adipocyte cell line expressing the uncoupling protein gene.

PubMed Central

Ross, S R; Choy, L; Graves, R A; Fox, N; Solevjeva, V; Klaus, S; Ricquier, D; Spiegelman, B M

1992-01-01

Transgenic mice were produced containing the adipocyte-specific regulatory region from the adipocyte P2 (aP2) gene linked to the simian virus 40 transforming genes. Most of the transgenic mice developed brown fat tumors (hibernomas) in their interscapular brown adipose tissue. Hibernoma formation was noticeable in some of the mice as early as 1 day after birth and most of the mice developed very large tumors by 1 month of age. All of the tumor tissue expressed the brown fat-specific uncoupling protein (UCP) gene as well as the aP2 gene. Several of the tumors have been used to establish cultured cell lines and at least one of these lines can be induced to differentiate into brown adipocytes. The cultured adipocytes express mRNA for UCP upon stimulation with N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate, norepinephrine, isoproterenol or D7114, a beta 3 adrenergic agonist. Thus, regulation of the key thermogenic gene UCP can now be studied in an established cell line. Images PMID:1323843

Transport of curcumin derivatives in Caco-2 cell monolayers.

PubMed

Zeng, Zhen; Shen, Zhe L; Zhai, Shuo; Xu, Jia L; Liang, Hui; Shen, Qin; Li, Qing Y

2017-08-01

Curcumin (Cur) is a strong natural antioxidant, who can prevent multiple diseases such as anti-cancer, anti-inflammatory, have a resistance to alzheimer's disease and various malignant diseases. But it has poor oral bioavailability due to its poor aqueous solubility, as well as instability. While its novel derivatives (CB and FE), showed better anti-tumor activity, better anti-oxidant activity and better stability than the original drug (Cur). The aim of this study was to study the intestinal transport of Cur, CB and FE using an in vitro Caco-2 cell monolayer model. The results showed that Cur had a lower permeability coefficient (1.13×10 -6 ±0.11×10 -6 cm/s) for apical-to-basolated (AP-BL) transport at 25μM, while the transport rate for AP to BL flux of CB (3.18×10 -6 ±0.31×10 -6 cm/s) and FE (5.28×10 -6 ±0.83×10 -6 cm/s) were significantly greater than that of Cur. The efflux ratio (ER) value at the concentration of 25μM was 1.31 for Cur, 1.26 for CB and 1.33 for FE, suggesting there was no active efflux involved in the translocation across the Caco-2 cell monolayers for the three compounds. Furthermore, the transport flux of CB and FE was in a concentration dependent manner, suggesting the intestinal transport mechanism in them was passive transport. In summary, the results demonstrated that both the intestinal permeability of CB and FE across Caco-2 cell monolayers was significantly improved compare to Cur. Thus they might show a higher oral bioavailability in vivo, and show the potential application in clinic or nutraceutical. Copyright © 2017 Elsevier B.V. All rights reserved.

14 CFR 29.1017 - Oil lines and fittings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Oil lines and fittings. 29.1017 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Oil System § 29.1017 Oil lines and fittings. (a) Each oil line must meet the requirements of § 29.993. (b) Breather lines must be arranged so that...

14 CFR 29.1017 - Oil lines and fittings.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Oil lines and fittings. 29.1017 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Oil System § 29.1017 Oil lines and fittings. (a) Each oil line must meet the requirements of § 29.993. (b) Breather lines must be arranged so that...

14 CFR 29.1017 - Oil lines and fittings.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Oil lines and fittings. 29.1017 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Oil System § 29.1017 Oil lines and fittings. (a) Each oil line must meet the requirements of § 29.993. (b) Breather lines must be arranged so that...

14 CFR 29.1017 - Oil lines and fittings.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Oil lines and fittings. 29.1017 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Oil System § 29.1017 Oil lines and fittings. (a) Each oil line must meet the requirements of § 29.993. (b) Breather lines must be arranged so that...

Transportation of part supply improvement in agricultural machinery assembly plant

NASA Astrophysics Data System (ADS)

Saysaman, Anusit; Chutima, Parames

2018-02-01

This research focused on the problem caused by the transportation of part supply in agricultural machinery assembly plant in Thailand, which is one of the processes that are critical to the whole production process. If poorly managed, it will affect transportation of part supply, the emergence of sink cost, quality problems, and the ability to respond to the needs of the customers in time. Since the competition in the agricultural machinery market is more intense, the efficiency of part transportation process has to be improved. In this study, the process of transporting parts of the plant was studied and it was found that the efficiency of the process of transporting parts from the sub assembly line to its main assembly line was 83%. The approach to the performance improvement is done by using the Lean tool to limit wastes based on the ECRS principle and applying pull production system by changing the transportation method to operate as milkrun for transportation of parts to synchronize with the part demands of the main assembly line. After the transportation of parts from sub-assembly line to the main assembly line was improved, the efficiency raised to 98% and transportation process cost was saved to 540,000 Baht per year.

Understanding and Using the New Guided-Inquiry AP Chemistry Laboratory Manual

ERIC Educational Resources Information Center

Cacciatore, Kristen L.

2014-01-01

To support teaching and learning in the advanced placement (AP) chemistry laboratory, the College Board published a laboratory manual, "AP Chemistry Guided-Inquiry Experiments: Applying the Science Practices," in 2013 as part of the redesigned course. This article provides a discussion of the rationale for the existence of the manual as…

Panel Discussion : Report of the APS Ad-Hoc Committee on LGBT Issues

NASA Astrophysics Data System (ADS)

Atherton, Tim; Barthelemy, Ramon; Garmon, Savannah; Reeves, Kyle; APS Ad-Hoc Committee on LGBT Issues Team

Following the presentation of the findings and recommendations of the APS Ad-Hoc Committee on LGBT Issues (C-LGBT) by Committee Chair Michael Falk, a panel discussion will be held featuring several members of the committee. The discussion will focus on how APS can best ensure the recommendations of the committee are carried out in a timely fashion and other ideas on future APS efforts toward LGBT inclusion in physics. Discussion topics will also include the research and other input that shaped the committee's findings and recommendations.

Cardioprotective effect of diadenosine tetraphosphate (AP4A) cardioplegia in isolated rat hearts.

PubMed

Ahmet, I; Sawa, Y; Nishimura, M; Matsuda, H

2000-01-01

Preischemic administration of diadenosine tetraphosphate (AP4A) has been shown to be cardioprotective. We evaluated the protective effect of AP4A when used as a cardioplegic adjuvant and tested contributions of the ATP-sensitive potassium channel (K ATP channel), adenosine receptor (AR), and purine 2y receptor (P2yR) to the effect of AP4A. Isolated buffer-perfused rat hearts were subjected to 23 min of ischemia (37 degrees C) followed by 20 min of reperfusion. Cardioplegia solution (St. Thomas Hospital solution) was infused during the first 3 min of ischemia. AP4A (10 microM) or AP4A with glibenclamide (K ATP channel blocker, 100 microM), 8-SPT (AR antagonist, 300 microM) or reactive blue (P2yR antagonist, 13 nM) were added to the cardioplegia solution. Compared with the cardioplegia solution alone, administration of AP4A with the solution significantly increased the recovery of rate-pressure production (75% +/- 11% vs 58% +/- 10%; P < 0.05) and dp/dt at the end of reperfusion, and reduced the leakage of creatine kinase (3.2 +/- 3.7 vs 13.2 +/- 10.1 IU/g; P < 0.05) during reperfusion. This effect was reversed by coadministration of glibenclamide or reactive blue but not 8-SPT. The addition of AP4A into the cardioplegia solution led to an added cardioprotective effect, either by opening the K ATP channel or by activating P2yR.

H- beam transport experiments in a solenoid low energy beam transport.

PubMed

Gabor, C; Back, J J; Faircloth, D C; Izaola, Z; Lawrie, S R; Letchford, A P

2012-02-01

The Front End Test Stand (FETS) is located at Rutherford Appleton Laboratory and aims for a high current, fast chopped 3 MeV H(-) ion beam suitable for future high power proton accelerators like ISIS upgrade. The main components of the front end are the Penning ion source, a low energy beam transport line, an radio-frequency quadrupole (RFQ) and a medium energy beam transport (MEBT) providing also a chopper section and rebuncher. FETS is in the stage of commissioning its low energy beam transport (LEBT) line consisting of three solenoids. The LEBT has to transport an H(-) high current beam (up to 60 mA) at 65 keV. This is the injection energy of the beam into the RFQ. The main diagnostics are slit-slit emittance scanners for each transversal plane. For optimizing the matching to the RFQ, experiments have been performed with a variety of solenoid settings to better understand the actual beam transport. Occasionally, source parameters such as extractor slit width and beam energy were varied as well. The paper also discusses simulations based on these measurements.

Using a Classroom Response System to Improve Multiple-Choice Performance in AP[R] Physics

ERIC Educational Resources Information Center

Bertrand, Peggy

2009-01-01

Participation in rigorous high school courses such as Advanced Placement (AP[R]) Physics increases the likelihood of college success, especially for students who are traditionally underserved. Tackling difficult multiple-choice exams should be part of any AP program because well-constructed multiple-choice questions, such as those on AP exams and…

Role of the AP-5 adaptor protein complex in late endosome-to-Golgi retrieval

PubMed Central

Hirst, Jennifer; Itzhak, Daniel N.; Antrobus, Robin; Borner, Georg H. H.

2018-01-01

The AP-5 adaptor protein complex is presumed to function in membrane traffic, but so far nothing is known about its pathway or its cargo. We have used CRISPR-Cas9 to knock out the AP-5 ζ subunit gene, AP5Z1, in HeLa cells, and then analysed the phenotype by subcellular fractionation profiling and quantitative mass spectrometry. The retromer complex had an altered steady-state distribution in the knockout cells, and several Golgi proteins, including GOLIM4 and GOLM1, were depleted from vesicle-enriched fractions. Immunolocalisation showed that loss of AP-5 led to impaired retrieval of the cation-independent mannose 6-phosphate receptor (CIMPR), GOLIM4, and GOLM1 from endosomes back to the Golgi region. Knocking down the retromer complex exacerbated this phenotype. Both the CIMPR and sortilin interacted with the AP-5–associated protein SPG15 in pull-down assays, and we propose that sortilin may act as a link between Golgi proteins and the AP-5/SPG11/SPG15 complex. Together, our findings suggest that AP-5 functions in a novel sorting step out of late endosomes, acting as a backup pathway for retromer. This provides a mechanistic explanation for why mutations in AP-5/SPG11/SPG15 cause cells to accumulate aberrant endolysosomes, and highlights the role of endosome/lysosome dysfunction in the pathology of hereditary spastic paraplegia and other neurodegenerative disorders. PMID:29381698

Human Papillomavirus Type 16 E6 Induces Self-Ubiquitination of the E6AP Ubiquitin-Protein Ligase

PubMed Central

Kao, Wynn H.; Beaudenon, Sylvie L.; Talis, Andrea L.; Huibregtse, Jon M.; Howley, Peter M.

2000-01-01

The E6 protein of the high-risk human papillomaviruses (HPVs) and the cellular ubiquitin-protein ligase E6AP form a complex which causes the ubiquitination and degradation of p53. We show here that HPV16 E6 promotes the ubiquitination and degradation of E6AP itself. The half-life of E6AP is shorter in HPV-positive cervical cancer cells than in HPV-negative cervical cancer cells, and E6AP is stabilized in HPV-positive cancer cells when expression of the viral oncoproteins is repressed. Expression of HPV16 E6 in cells results in a threefold decrease in the half-life of transfected E6AP. E6-mediated degradation of E6AP requires (i) the binding of E6 to E6AP, (ii) the catalytic activity of E6AP, and (iii) activity of the 26S proteasome, suggesting that E6-E6AP interaction results in E6AP self-ubiquitination and degradation. In addition, both in vitro and in vivo experiments indicate that E6AP self-ubiquitination results primarily from an intramolecular transfer of ubiquitin from the active-site cysteine to one or more lysine residues; however, intermolecular transfer can also occur in the context of an E6-mediated E6AP multimer. Finally, we demonstrate that an E6 mutant that is able to immortalize human mammary epithelial cells but is unable to degrade p53 retains its ability to bind and degrade E6AP, raising the possibility that E6-mediated degradation of E6AP contributes to its ability to transform mammalian cells. PMID:10864652

Molecular Basis for Association of PIPKIγ-p90 with Clathrin Adaptor AP-2*

PubMed Central

Kahlfeldt, Nina; Vahedi-Faridi, Ardeschir; Koo, Seong Joo; Schäfer, Johannes G.; Krainer, Georg; Keller, Sandro; Saenger, Wolfram; Krauss, Michael; Haucke, Volker

2010-01-01

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is an essential determinant in clathrin-mediated endocytosis (CME). In mammals three type I phosphatidylinositol-4-phosphate 5-kinase (PIPK) enzymes are expressed, with the Iγ-p90 isoform being highly expressed in the brain where it regulates synaptic vesicle (SV) exo-/endocytosis at nerve terminals. How precisely PI(4,5)P2 metabolism is controlled spatially and temporally is still uncertain, but recent data indicate that direct interactions between type I PIPK and components of the endocytic machinery, in particular the AP-2 adaptor complex, are involved. Here we demonstrated that PIPKIγ-p90 associates with both the μ and β2 subunits of AP-2 via multiple sites. Crystallographic data show that a peptide derived from the splice insert of the human PIPKIγ-p90 tail binds to a cognate recognition site on the sandwich subdomain of the β2 appendage. Partly overlapping aromatic and hydrophobic residues within the same peptide also can engage the C-terminal sorting signal binding domain of AP-2μ, thereby potentially competing with the sorting of conventional YXXØ motif-containing cargo. Biochemical and structure-based mutagenesis analysis revealed that association of the tail domain of PIPKIγ-p90 with AP-2 involves both of these sites. Accordingly the ability of overexpressed PIPKIγ tail to impair endocytosis of SVs in primary neurons largely depends on its association with AP-2β and AP-2μ. Our data also suggest that interactions between AP-2 and the tail domain of PIPKIγ-p90 may serve to regulate complex formation and enzymatic activity. We postulate a model according to which multiple interactions between PIPKIγ-p90 and AP-2 lead to spatiotemporally controlled PI(4,5)P2 synthesis during clathrin-mediated SV endocytosis. PMID:19903820

Structural modeling and molecular simulation analysis of HvAP2/EREBP from barley.

PubMed

Pandey, Bharati; Sharma, Pradeep; Tyagi, Chetna; Goyal, Sukriti; Grover, Abhinav; Sharma, Indu

2016-06-01

AP2/ERF transcription factors play a critical role in plant development and stress adaptation. This study reports the three-dimensional ab initio-based model of AP2/EREBP protein of barley and its interaction with DNA. Full-length coding sequence of HvAP2/EREBP gene isolated from two Indian barley cultivars, RD 2503 and RD 31, was used to model the protein. Of five protein models obtained, the one with lowest C-score was chosen for further analysis. The N- and C-terminal regions of HvAP2 protein were found to be highly disordered. The dynamic properties of AP2/EREBP and its interaction with DNA were investigated by molecular dynamics simulation. Analysis of trajectories from simulation yielded the equilibrated conformation between 2-10ns for protein and 7-15ns for protein-DNA complex. We established relationship between DNA having GCC box and DNA-binding domain of HvAP2/EREBP was established by modeling 11-base-pair-long nucleotide sequence and HvAP2/EREBP protein using ab initio method. Analysis of protein-DNA interaction showed that a β-sheet motif constituting amino acid residues THR105, ARG100, ARG93, and ARG83 seems to play important role in stabilizing the complex as they form strong hydrogen bond interactions with the DNA motif. Taken together, this study provides first-hand comprehensive information detailing structural conformation and interactions of HvAP2/EREBP proteins in barley. The study intensifies the role of computational approaches for preliminary examination of unknown proteins in the absence of experimental information. It also provides molecular insight into protein-DNA binding for understanding and enhancing abiotic stress resistance for improving the water use efficiency in crop plants.

14 CFR 25.1017 - Oil lines and fittings.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Oil lines and fittings. 25.1017 Section 25... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Oil System § 25.1017 Oil lines and fittings. (a) Each oil line must meet the requirements of § 25.993 and each oil line and fitting in any designated...

14 CFR 25.1017 - Oil lines and fittings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Oil lines and fittings. 25.1017 Section 25... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Oil System § 25.1017 Oil lines and fittings. (a) Each oil line must meet the requirements of § 25.993 and each oil line and fitting in any designated...

14 CFR 25.1017 - Oil lines and fittings.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Oil lines and fittings. 25.1017 Section 25... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Oil System § 25.1017 Oil lines and fittings. (a) Each oil line must meet the requirements of § 25.993 and each oil line and fitting in any designated...

14 CFR 25.1017 - Oil lines and fittings.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Oil lines and fittings. 25.1017 Section 25... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Oil System § 25.1017 Oil lines and fittings. (a) Each oil line must meet the requirements of § 25.993 and each oil line and fitting in any designated...

Segmental dependent transport of low permeability compounds along the small intestine due to P-glycoprotein: the role of efflux transport in the oral absorption of BCS class III drugs.

PubMed

Dahan, Arik; Amidon, Gordon L

2009-01-01

The purpose of this study was to investigate the role of P-gp efflux in the in vivo intestinal absorption process of BCS class III P-gp substrates, i.e. high-solubility low-permeability drugs. The in vivo permeability of two H (2)-antagonists, cimetidine and famotidine, was determined by the single-pass intestinal perfusion model in different regions of the rat small intestine, in the presence or absence of the P-gp inhibitor verapamil. The apical to basolateral (AP-BL) and the BL-AP transport of the compounds in the presence or absence of various efflux transporters inhibitors (verapamil, erythromycin, quinidine, MK-571 and fumitremorgin C) was investigated across Caco-2 cell monolayers. P-gp expression levels in the different intestinal segments were confirmed by immunoblotting. Cimetidine and famotidine exhibited segmental dependent permeability through the gut wall, with decreased P(eff) in the distal ileum in comparison to the proximal regions of the intestine. Coperfusion of verapamil with the drugs significantly increased the permeability in the ileum, while no significant change in the jejunal permeability was observed. Both drugs exhibited significantly greater BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Concentration dependent decrease of this secretion was obtained by the P-gp inhibitors verapamil, erythromycin and quinidine, while no effect was evident by the MRP2 inhibitor MK-571 and the BCRP inhibitor FTC, indicating that P-gp is the transporter mediates the intestinal efflux of cimetidine and famotidine. P-gp levels throughout the intestine were inversely related to the in vivo permeability of the drugs from the different segments. The data demonstrate that for these high-solubility low-permeability P-gp substrates, P-gp limits in vivo intestinal absorption in the distal segments of the small intestine; however P-gp plays a minimal role in the proximal intestinal segments due to significant lower P-gp expression levels

Detection and functional characterization of Pgp1 (ABCB1) and MRP3 (ABCC3) efflux transporters in the PLHC-1 fish hepatoma cell line.

PubMed

Zaja, Roko; Klobucar, Roberta Sauerborn; Smital, Tvrtko

2007-03-30

The PLHC-1 hepatoma cell line derived from topminnow (Poeciliopsis lucida) is one of the most frequently used fish cell lines in aquatic ecotoxicology. These cells have been well characterized regarding the presence of phase I and phase II enzymes involved in the metabolism of xenobiotics. However, the presence of the ABC transport proteins possibly involved in the MultiXenobiotic Resistance (MXR) mechanism as phase III of cellular detoxification has never been described in the PLHC-1 cells. The main goal of this study was the detection and functional characterization of toxicologically relevant xenobiotic efflux transporters from ABCB and ABCC subfamily in the PLHC-1 cells. Using specific primer pairs two PCR products 1769 and 1023bp in length were successfully cloned and sequenced. Subsequent multiple alignment and phylogenetic analysis showed that these sequences share a high degree of homology with the P-glycoprotein (Pgp1; ABCB1) and the MRP3 (ABCC3). Functional experiments with fluorescent model substrates and specific inhibitors were used to verify that transport activities of Pgp- and MRP-related proteins are indeed present in PLHC-1 cells. Accumulation or efflux/retention rates of rhodamine 123, calcein-AM or monochlorbimane were time- and concentration-dependent. Cyclosporine A, MK571, verapamil, reversine 205, indomethacine and probenecid were used as specific inhibitors of Pgp1 and/or MRPs transport activities, resulting in a dose dependent inhibition of related transport activities in PLHC-1 cells. Similar to mammalian systems, the obtained IC(50) values were in the lower micromolar range. Taken together these data demonstrate that: (1) the PLHC-1 cells do express a functional MXR mechanism mediated by toxicologically relevant ABC efflux transporters; and (2) the presence of all three critical phases of cellular detoxification additionally affirms the PLHC-1 cells as a reliable in vitro model in aquatic toxicology.

Galactic evolution of oxygen. OH lines in 3D hydrodynamical model atmospheres

NASA Astrophysics Data System (ADS)

González Hernández, J. I.; Bonifacio, P.; Ludwig, H.-G.; Caffau, E.; Behara, N. T.; Freytag, B.

2010-09-01

Context. Oxygen is the third most common element in the Universe. The measurement of oxygen lines in metal-poor unevolved stars, in particular near-UV OH lines, can provide invaluable information about the properties of the Early Galaxy. Aims: Near-UV OH lines constitute an important tool to derive oxygen abundances in metal-poor dwarf stars. Therefore, it is important to correctly model the line formation of OH lines, especially in metal-poor stars, where 3D hydrodynamical models commonly predict cooler temperatures than plane-parallel hydrostatic models in the upper photosphere. Methods: We have made use of a grid of 52 3D hydrodynamical model atmospheres for dwarf stars computed with the code CO5BOLD, extracted from the more extended CIFIST grid. The 52 models cover the effective temperature range 5000-6500 K, the surface gravity range 3.5-4.5 and the metallicity range -3 < [Fe/H] < 0. Results: We determine 3D-LTE abundance corrections in all 52 3D models for several OH lines and ion{Fe}{i} lines of different excitation potentials. These 3D-LTE corrections are generally negative and reach values of roughly -1 dex (for the OH 3167 with excitation potential of approximately 1 eV) for the higher temperatures and surface gravities. Conclusions: We apply these 3D-LTE corrections to the individual O abundances derived from OH lines of a sample the metal-poor dwarf stars reported in Israelian et al. (1998, ApJ, 507, 805), Israelian et al. (2001, ApJ, 551, 833) and Boesgaard et al. (1999, AJ, 117, 492) by interpolating the stellar parameters of the dwarfs in the grid of 3D-LTE corrections. The new 3D-LTE [O/Fe] ratio still keeps a similar trend as the 1D-LTE, i.e., increasing towards lower [Fe/H] values. We applied 1D-NLTE corrections to 3D ion{Fe}{i} abundances and still see an increasing [O/Fe] ratio towards lower metallicites. However, the Galactic [O/Fe] ratio must be revisited once 3D-NLTE corrections become available for OH and Fe lines for a grid of 3D

STREAK CAMERA MEASUREMENTS OF THE APS PC GUN DRIVE LASER

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

Dooling, J. C.; Lumpkin, A. H.

We report recent pulse-duration measurements of the APS PC Gun drive laser at both second harmonic and fourth harmonic wavelengths. The drive laser is a Nd:Glass-based chirped pulsed amplifier (CPA) operating at an IR wavelength of 1053 nm, twice frequency-doubled to obtain UV output for the gun. A Hamamatsu C5680 streak camera and an M5675 synchroscan unit are used for these measurements; the synchroscan unit is tuned to 119 MHz, the 24th subharmonic of the linac s-band operating frequency. Calibration is accomplished both electronically and optically. Electronic calibration utilizes a programmable delay line in the 119 MHz rf path. Themore » optical delay uses an etalon with known spacing between reflecting surfaces and is coated for the visible, SH wavelength. IR pulse duration is monitored with an autocorrelator. Fitting the streak camera image projected profiles with Gaussians, UV rms pulse durations are found to vary from 2.1 ps to 3.5 ps as the IR varies from 2.2 ps to 5.2 ps.« less

CMOS-APS Detectors for Solar Physics: Lessons Learned during the SWAP Preflight Calibration

NASA Astrophysics Data System (ADS)

de Groof, A.; Berghmans, D.; Nicula, B.; Halain, J.-P.; Defise, J.-M.; Thibert, T.; Schühle, U.

2008-05-01

CMOS-APS imaging detectors open new opportunities for remote sensing in solar physics beyond what classical CCDs can provide, offering far less power consumption, simpler electronics, better radiation hardness, and the possibility of avoiding a mechanical shutter. The SWAP telescope onboard the PROBA2 technology demonstration satellite of the European Space Agency will be the first actual implementation of a CMOS-APS detector for solar physics in orbit. One of the goals of the SWAP project is precisely to acquire experience with the CMOS-APS technology in a real-live space science context. Such a precursor mission is essential in the preparation of missions such as Solar Orbiter where the extra CMOS-APS functionalities will be hard requirements. The current paper concentrates on specific CMOS-APS issues that were identified during the SWAP preflight calibration measurements. We will discuss the different readout possibilities that the CMOS-APS detector of SWAP provides and their associated pros and cons. In particular we describe the “image lag” effect, which results in a contamination of each image with a remnant of the previous image. We have characterised this effect for the specific SWAP implementation and we conclude with a strategy on how to successfully circumvent the problem and actually take benefit of it for solar monitoring.

Ecto-diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A)-hydrolase is expressed as an ectoenzyme in a variety of mammalian and human cells and adds new aspects to the turnover of Ap4A.

PubMed

von Drygalski, A; Ogilvie, A

2000-01-01

Ap4A and other dinucleotides participate in the regulation of hemostasis and blood pressure control. With the exception of two previously reported surface anchored ectoAp4A-hydrolases on bovine aortic endothelial and chromaffine cells, all Ap4A-hydrolases reported are intracellular or freely soluble. We demonstrated that ectoAp4A-hydrolases are present on a broad variety of cell types of different species: rat mesangial, bovine corneal epithelial, human Hep-G2 and peridontal cells. Ectoenzyme properties were evaluated on rat mesangium cells. Chromatography of purified plasma membranes on Sephacel 300 resulted in enrichment of ectoAp4A-hydrolase and in separation from ectoATPase. In contrast to ATPase, Ap4A-hydrolase was stable at room temperature. EctoAp4A-hydrolase also recognized ATP as substrate, and therefore is not highly specific. The molecular weight was 180 kD. Unlike ectoAMPase ectoAp4A-hydrolase was not attached via a glycosyl-phosphatidylinositol (GPI)-moiety. Concentrations of PI-PLC 10-100-fold higher than effective for ectoAMPase cleavage (10-100 mU/ml) plus extensively extended incubation times up to eight hours did not result in cleavage of ectoAp4A-hydrolase. The enzyme ectoAp4A-hydrolase might presage a direction for pharmaceutical manipulation in the control of blood pressure and hemostasis.

AP1000{sup R} severe accident features and post-Fukushima considerations

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

Scobel, J. H.; Schulz, T. L.; Williams, M. G.

2012-07-01

The AP1000{sup R} passive nuclear power plant is uniquely equipped to withstand an extended station blackout scenario such as the events following the earthquake and tsunami at Fukushima without compromising core and containment integrity. The AP1000 plant shuts down the reactor, cools the core, containment and spent fuel pool for more than 3 days using passive systems that do not require AC or DC power or operator actions. Following this passive coping period, minimal operator actions are needed to extend the operation of the passive features to 7 days using installed equipment. To provide defense-in-depth for design extension conditions, themore » AP1000 plant has engineered features that mitigate the effects of core damage. Engineered features retain damaged core debris within the reactor vessel as a key feature. Other aspects of the design protect containment integrity during severe accidents, including unique features of the AP1000 design relative to passive containment cooling with water and air, and hydrogen management. (authors)« less

AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

PubMed Central

Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

2016-01-01

The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

Aviation Safety Program: Weather Accident Prevention (WxAP) Development of WxAP System Architecture And Concepts of Operation

NASA Technical Reports Server (NTRS)

Grantier, David

2003-01-01

This paper presents viewgraphs on the development of the Weather Accident Prevention (WxAP) System architecture and Concept of Operation (CONOPS) activities. The topics include: 1) Background Information on System Architecture/CONOPS Activity; 2) Activity Work in Progress; and 3) Anticipated By-Products.

77 FR 59391 - Delta Air Lines, Inc., Continental Airlines, Inc., JetBlue Airways Corporation, United Air Lines...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-27

... lawfulness of the rates charged by the Respondent for transportation of jet or aviation turbine fuel on its..., Inc., Continental Airlines, Inc., JetBlue Airways Corporation, United Air Lines, Inc., US Airways, Inc... Airlines, Inc., JetBlue Airways Corporation, United Air Lines, Inc., and US Airways, Inc. (collectively...

AP-1 Oligodeoxynucleotides Reduce Aortic Elastolysis in a Murine Model of Marfan Syndrome.

PubMed

Arif, Rawa; Zaradzki, Marcin; Remes, Anca; Seppelt, Philipp; Kunze, Reiner; Schröder, Hannes; Schwill, Simon; Ensminger, Stephan M; Robinson, Peter N; Karck, Matthias; Müller, Oliver J; Hecker, Markus; Wagner, Andreas H; Kallenbach, Klaus

2017-12-15

Marfan syndrome is characterized by high expression of matrix metalloproteinases (MMPs) in aortic smooth muscle cells (AoSMCs) associated with medial elastolysis and aortic root aneurysm. We aimed to reduce aortic elastolysis through decrease of MMP expression with decoy oligodeoxynucleotides (dODNs) neutralizing the transcription factor activating factor-1 (AP-1). AP-1 abundance in nuclear extracts as well as MMP-2 and MMP-9 expression were significantly increased in isolated mAoSMC of mgR/mgR Marfan mice compared to wild-type cells. Exposure to AP-1 neutralizing dODNs resulted in a significant reduction of basal and interleukin-1β-stimulated MMP expression and activity in mAoSMCs. Moreover, increased migration and formation of superoxide radical anions was substantially decreased in mAoSMCs by AP-1 dODN treatment. Aortic grafts from donor Marfan mice were treated with AP-1- dODN ex vivo and implanted as infrarenal aortic interposition grafts in mgR/mgR mice. Pretreatment of aortic grafts with AP-1 dODN led to reduced elastolysis, macrophage infiltration, and MMP activity. Permeability of the endothelial monolayer was increased for dODN in mgR/mgR aortae with observed loss of tight junction proteins ZO-1 and occludin, enabling dODN to reach the tunica media. Targeting AP-1 activity offers a new potential strategy to treat the vascular phenotype associated with Marfan syndrome. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Structural Determinants of DNA Binding by a P. falciparum ApiAP2 Transcriptional Regulator

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

Lindner, Scott E.; De Silva, Erandi K.; Keck, James L.

2010-11-05

Putative transcription factors have only recently been identified in the Plasmodium spp., with the major family of regulators comprising the Apicomplexan Apetala2 (AP2) proteins. To better understand the DNA-binding mechanisms of these transcriptional regulators, we characterized the structure and in vitro function of an AP2 DNA-binding domain from a prototypical Apicomplexan AP2 protein, PF14{_}0633 from Plasmodium falciparum. The X-ray crystal structure of the PF14{_}0633 AP2 domain bound to DNA reveals a {beta}-sheet fold that binds the DNA major groove through base-specific and backbone contacts; a prominent {alpha}-helix supports the {beta}-sheet structure. Substitution of predicted DNA-binding residues with alanine weakened ormore » eliminated DNA binding in solution. In contrast to plant AP2 domains, the PF14{_}0633 AP2 domain dimerizes upon binding to DNA through a domain-swapping mechanism in which the {alpha}-helices of the AP2 domains pack against the {beta}-sheets of the dimer mates. DNA-induced dimerization of PF14{_}0633 may be important for tethering two distal DNA loci together in the nucleus and/or for inducing functional rearrangements of its domains to facilitate transcriptional regulation. Consistent with a multisite binding mode, at least two copies of the consensus sequence recognized by PF14{_}0633 are present upstream of a previously identified group of sporozoite-stage genes. Taken together, these findings illustrate how Plasmodium has adapted the AP2 DNA-binding domain for genome-wide transcriptional regulation.« less

The cell line NCl-H441 is a useful in vitro model for transport studies of human distal lung epithelial barrier.

PubMed

Salomon, Johanna J; Muchitsch, Viktoria E; Gausterer, Julia C; Schwagerus, Elena; Huwer, Hanno; Daum, Nicole; Lehr, Claus-Michael; Ehrhardt, Carsten

2014-03-03

The lack of a well characterized, continuously growing in vitro model of human distal lung epithelial phenotype constitutes a serious limitation in the area of inhalation biopharmaceutics, particularly in the context of transepithelial transport studies. Here, we investigated if a human lung adenocarcinoma cell line, NCl-H441, has potential to serve as an in vitro model of human distal lung epithelium. The development of barrier properties was studied by immunocytochemistry (ICC) against the junction proteins zonula occludens protein 1 (ZO-1) and E-cadherin and measurement of transepithelial electrical resistance (TEER). Moreover, transport studies with the paracellular marker compounds fluorescein sodium and fluorescein isothiocyanate (FITC)-labeled dextrans of molecular weights ranging from 4 to 70 kDa were carried out. The expression of P-glycoprotein (P-gp; ABCB1) and organic cation transporters (OCT/Ns; SLC22A1-A5) was investigated by ICC and immunoblot. P-gp function was assessed by monolayer release and bidirectional transport studies using rhodamine 123 (Rh123) and the inhibitors verapamil and LY335979. Uptake of 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP(+)) was measured, in order to assess organic cation transporter function in vitro. Furthermore, the inhibitory potential of several organic cations on ASP(+) uptake was studied. NCl-H441 cells, when grown under liquid-covered conditions, formed confluent, electrically tight monolayers with peak TEER values of approximately 1000 Ω·cm(2), after 8-12 days in culture. These monolayers were able to differentiate paracellularly transported substrates according to their molecular weight. Presence of P-gp, OCT1, OCT2, OCT3, OCTN1, and OCTN2 was confirmed by Western blot and ICC and was similar to data from freshly isolated human alveolar epithelial cells in primary culture. Rh123 release from NCI-H441 monolayers was time-dependent and showed low, albeit significant attenuation by both inhibitors

Back to the Future: Merit or Equity in AP Social Studies?

ERIC Educational Resources Information Center

Stevens, Robert

2013-01-01

In an effort to address severe budget deficits at both the state and local levels, schools and educational programs are being asked to trim budgets. The Advanced Placement Program is one program that will certainly be scrutinized. This article presents a general overview of AP social studies, a brief history of the AP social studies program, and…

Airborne Precision Spacing (APS) Dependent Parallel Arrivals (DPA)

NASA Technical Reports Server (NTRS)

Smith, Colin L.

2012-01-01

The Airborne Precision Spacing (APS) team at the NASA Langley Research Center (LaRC) has been developing a concept of operations to extend the current APS concept to support dependent approaches to parallel or converging runways along with the required pilot and controller procedures and pilot interfaces. A staggered operations capability for the Airborne Spacing for Terminal Arrival Routes (ASTAR) tool was developed and designated as ASTAR10. ASTAR10 has reached a sufficient level of maturity to be validated and tested through a fast-time simulation. The purpose of the experiment was to identify and resolve any remaining issues in the ASTAR10 algorithm, as well as put the concept of operations through a practical test.

COP9 signalosome subunit 6 (CSN6) regulates E6AP/UBE3A in cervical cancer.

PubMed

Gao, Shujun; Fang, Lekun; Phan, Liem Minh; Qdaisat, Aiham; Yeung, Sai-Ching J; Lee, Mong-Hong

2015-09-29

Cervical cancer is one of the leading causes of cancer death in women. Human papillomaviruses (HPVs) are the major cause in almost 99.7% of cervical cancer. E6 oncoprotein of HPV and E6-associated protein (E6AP) are critical in causing p53 degradation and malignancy. Understanding the E6AP regulation is critical to develop treating strategy for cervical cancer patients. The COP9 signalosome subunit 6 (CSN6) is involved in ubiquitin-mediated protein degradation. We found that both CSN6 and E6AP are overexpressed in cervical cancer. We characterized that CSN6 associated with E6AP and stabilized E6AP expression by reducing E6AP poly-ubiquitination, thereby regulating p53 activity in cell proliferation and apoptosis. Mechanistic studies revealed that CSN6-E6AP axis can be regulated by EGF/Akt signaling. Furthermore, inhibition of CSN6-E6AP axis hinders cervical cancer growth in mice. Taken together, our results indicate that CSN6 is a positive regulator of E6AP and is important for cervical cancer development.

Degraded λ-carrageenan activates NF-κB and AP-1 pathways in macrophages and enhances LPS-induced TNF-α secretion through AP-1.

PubMed

Chen, Haimin; Wang, Feng; Mao, Haihua; Yan, Xiaojun

2014-07-01

Carrageenan (CGN), a high molecular weight sulfated polysaccharide, is a traditional ingredient used in food industry. Its degraded forms have been identified as potential carcinogens, although the mechanism remains unclear. The effects of degraded λ-carrageenan (λ-dCGN) on murine RAW264.7 cells and human THP-1-derived macrophage cells were investigated by studying its actions on tumor necrosis factor alpha (TNF-α) secretion, Toll-like receptor 4 (TLR4) expression, and activation of nuclear factor-κb (NF-κB) and activation protein-1 (AP-1) pathways. We found that λ-dCGN was much stronger than native λ-CGN in the activation of macrophages to secrete TNF-α. Treatment of RAW264.7 cells with λ-dCGN resulted in the upregulation of TLR4, CD14 and MD-2 expressions, but it did not increase the binding of lipopolysacchride (LPS) with macrophages. Meanwhile, λ-dCGN treatment activated NF-κB via B-cell lymphoma/leukemia 10 (Bcl10) and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation. In addition, λ-dCGN induced extracellular signal-regulated kinases/1/2/mitogen-activated protein kinases (ERK1/2/MAPK) and AP-1 activation. Interestingly, pretreatment of RAW264.7 cells with λ-dCGN markedly enhanced LPS-stimulated TNF-α secretion. This pretreatment resulted in the enhanced phosphorylation of ERK1/2 and c-Jun N-terminal kinase (JNK) and intensified activation of AP-1. λ-dCGN induced an inflammatory reaction via both NF-κB and AP-1, and enhanced the inflammatory effect of LPS through AP-1 activation. The study demonstrated the role of λ-dCGN to induce the inflammatory reaction and to aggravate the effect of LPS on macrophages, suggesting that λ-dCGN produced during food processing and gastric digestion may be a safety concern. Copyright © 2014 Elsevier B.V. All rights reserved.

A method of semi-quantifying β-AP in brain PET-CT 11C-PiB images.

PubMed

Jiang, Jiehui; Lin, Xiaoman; Wen, Junlin; Huang, Zhemin; Yan, Zhuangzhi

2014-01-01

Alzheimer's disease (AD) is a common health problem for elderly populations. Positron emission tomography-computed tomography (PET-CT)11C-PiB for beta-P (amyloid-β peptide, β-AP) imaging is an advanced method to diagnose AD in early stage. However, in practice radiologists lack a standardized value to semi-quantify β-AP. This paper proposes such a standardized value: SVβ-AP. This standardized value measures the mean ratio between the dimension of β-AP areas in PET and CT images. A computer aided diagnosis approach is also proposed to achieve SVβ-AP. A simulation experiment was carried out to pre-test the technical feasibility of the CAD approach and SVβ-AP. The experiment results showed that it is technically feasible.

241-AP Tank Farm Construction Extent of Condition Review for Tank Integrity

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

Barnes, Travis J.; Gunter, Jason R.; Reeploeg, Gretchen E.

2014-04-04