Sample records for aare kuusik luule

  1. Novel (ovario) leukodystrophy related to AARS2 mutations

    PubMed Central

    Dallabona, Cristina; Diodato, Daria; Kevelam, Sietske H.; Haack, Tobias B.; Wong, Lee-Jun; Salomons, Gajja S.; Baruffini, Enrico; Melchionda, Laura; Mariotti, Caterina; Strom, Tim M.; Meitinger, Thomas; Prokisch, Holger; Chapman, Kim; Colley, Alison; Rocha, Helena; Őunap, Katrin; Schiffmann, Raphael; Salsano, Ettore; Savoiardo, Mario; Hamilton, Eline M.; Abbink, Truus E. M.; Wolf, Nicole I.; Ferrero, Ileana; Lamperti, Costanza; Zeviani, Massimo; Vanderver, Adeline

    2014-01-01

    Objectives: The study was focused on leukoencephalopathies of unknown cause in order to define a novel, homogeneous phenotype suggestive of a common genetic defect, based on clinical and MRI findings, and to identify the causal genetic defect shared by patients with this phenotype. Methods: Independent next-generation exome-sequencing studies were performed in 2 unrelated patients with a leukoencephalopathy. MRI findings in these patients were compared with available MRIs in a database of unclassified leukoencephalopathies; 11 patients with similar MRI abnormalities were selected. Clinical and MRI findings were investigated. Results: Next-generation sequencing revealed compound heterozygous mutations in AARS2 encoding mitochondrial alanyl-tRNA synthetase in both patients. Functional studies in yeast confirmed the pathogenicity of the mutations in one patient. Sanger sequencing revealed AARS2 mutations in 4 of the 11 selected patients. The 6 patients with AARS2 mutations had childhood- to adulthood-onset signs of neurologic deterioration consisting of ataxia, spasticity, and cognitive decline with features of frontal lobe dysfunction. MRIs showed a leukoencephalopathy with striking involvement of left-right connections, descending tracts, and cerebellar atrophy. All female patients had ovarian failure. None of the patients had signs of a cardiomyopathy. Conclusions: Mutations in AARS2 have been found in a severe form of infantile cardiomyopathy in 2 families. We present 6 patients with a new phenotype caused by AARS2 mutations, characterized by leukoencephalopathy and, in female patients, ovarian failure, indicating that the phenotypic spectrum associated with AARS2 variants is much wider than previously reported. PMID:24808023

  2. Alkali-aggregate reactivity (AAR) facts book.

    DOT National Transportation Integrated Search

    2013-03-01

    This document provides detailed information on alkali-aggregate reactivity (AAR). It primarily discusses alkali-silica reaction (ASR), covering the chemistry, symptoms, test methods, prevention, specifications, diagnosis and prognosis, and mitigation...

  3. Structural basis for dual roles of Aar2p in U5 snRNP assembly

    PubMed Central

    Weber, Gert; Cristão, Vanessa F.; Santos, Karine F.; Jovin, Sina Mozaffari; Heroven, Anna C.; Holton, Nicole; Lührmann, Reinhard; Beggs, Jean D.; Wahl, Markus C.

    2013-01-01

    Yeast U5 small nuclear ribonucleoprotein particle (snRNP) is assembled via a cytoplasmic precursor that contains the U5-specific Prp8 protein but lacks the U5-specific Brr2 helicase. Instead, pre-U5 snRNP includes the Aar2 protein not found in mature U5 snRNP or spliceosomes. Aar2p and Brr2p bind competitively to a C-terminal region of Prp8p that comprises consecutive RNase H-like and Jab1/MPN-like domains. To elucidate the molecular basis for this competition, we determined the crystal structure of Aar2p in complex with the Prp8p RNase H and Jab1/MPN domains. Aar2p binds on one side of the RNase H domain and extends its C terminus to the other side, where the Jab1/MPN domain is docked onto a composite Aar2p–RNase H platform. Known Brr2p interaction sites of the Jab1/MPN domain remain available, suggesting that Aar2p-mediated compaction of the Prp8p domains sterically interferes with Brr2p binding. Moreover, Aar2p occupies known RNA-binding sites of the RNase H domain, and Aar2p interferes with binding of U4/U6 di-snRNA to the Prp8p C-terminal region. Structural and functional analyses of phospho-mimetic mutations reveal how phosphorylation reduces affinity of Aar2p for Prp8p and allows Brr2p and U4/U6 binding. Our results show how Aar2p regulates both protein and RNA binding to Prp8p during U5 snRNP assembly. PMID:23442228

  4. Animation Augmented Reality Book Model (AAR Book Model) to Enhance Teamwork

    ERIC Educational Resources Information Center

    Chujitarom, Wannaporn; Piriyasurawong, Pallop

    2017-01-01

    This study aims to synthesize an Animation Augmented Reality Book Model (AAR Book Model) to enhance teamwork and to assess the AAR Book Model to enhance teamwork. Samples are five specialists that consist of one animation specialist, two communication and information technology specialists, and two teaching model design specialists, selected by…

  5. The Automated Aircraft Rework System (AARS): A system integration approach

    NASA Technical Reports Server (NTRS)

    Benoit, Michael J.

    1994-01-01

    The Mercer Engineering Research Center (MERC), under contract to the United States Air Force (USAF) since 1989, has been actively involved in providing the Warner Robins Air Logistics Center (WR-ALC) with a robotic workcell designed to perform rework automated defastening and hole location/transfer operations on F-15 wings. This paper describes the activities required to develop and implement this workcell, known as the Automated Aircraft Rework System (AARS). AARS is scheduled to be completely installed and in operation at WR-ALC by September 1994.

  6. A novel AARS mutation in a family with dominant myeloneuropathy.

    PubMed

    Motley, William W; Griffin, Laurie B; Mademan, Inès; Baets, Jonathan; De Vriendt, Els; De Jonghe, Peter; Antonellis, Anthony; Jordanova, Albena; Scherer, Steven S

    2015-05-19

    To determine the genetic cause of neurodegeneration in a family with myeloneuropathy. We studied 5 siblings in a family with a mild, dominantly inherited neuropathy by clinical examination and electrophysiology. One patient had a sural nerve biopsy. After ruling out common genetic causes of axonal Charcot-Marie-Tooth disease, we sequenced 3 tRNA synthetase genes associated with neuropathy. All affected family members had a mild axonal neuropathy, and 3 of 4 had lower extremity hyperreflexia, evidence of a superimposed myelopathy. A nerve biopsy showed evidence of chronic axonal loss. All affected family members had a heterozygous missense mutation c.304G>C (p.Gly102Arg) in the alanyl-tRNA synthetase (AARS) gene; this allele was not identified in unaffected individuals or control samples. The equivalent change in the yeast ortholog failed to complement a strain of yeast lacking AARS function, suggesting that the mutation is damaging. A novel mutation in AARS causes a mild myeloneuropathy, a novel phenotype for patients with mutations in one of the tRNA synthetase genes. © 2015 American Academy of Neurology.

  7. IGFBP-1 hyperphosphorylation in response to leucine deprivation is mediated by the AAR pathway

    PubMed Central

    Malkani, Niyati; Jansson, Thomas; Gupta, Madhulika B.

    2017-01-01

    Insulin-like growth factor-1 (IGF-I) is the key regulator of fetal growth. IGF-I bioavailability is markedly diminished by IGF binding protein-1 (IGFBP-1) phosphorylation. Leucine deprivation strongly induces IGFBP-1hyperphosphorylation, and plays an important role in fetal growth restriction (FGR). FGR is characterized by decreased amino acid availability, which activates the amino acid response (AAR) and inhibits the mechanistic target of rapamycin (mTOR) pathway. We investigated the role of AAR and mTOR in mediating IGFBP-1 secretion and phosphorylation in HepG2 cells in leucine deprivation. mTOR inhibition (rapamycin or raptor+rictor siRNA), or activation (DEPTOR siRNA) demonstrated a role of mTOR in leucine deprivation-induced IGFBP-1 secretion but not phosphorylation. When the AAR was blocked (U0126, or ERK/GCN2 siRNA), both IGFBP-1 secretion and phosphorylation (Ser101/Ser119/Ser169) due to leucine deprivation were prevented. CK2 inhibition by TBB also attenuated IGFBP-1 phosphorylation in leucine deprivation. These results suggest that the AAR and mTOR independently regulate IGFBP-1 secretion and phosphorylation in leucine deprivation. PMID:25957086

  8. Chemoinformatics Profiling of the Chromone Nucleus as a MAO-B/A2AAR Dual Binding Scaffold

    PubMed Central

    Cruz-Monteagudo, Maykel; Borges, Fernanda; Cordeiro, M. Natália D. S.; Helguera, Aliuska Morales; Tejera, Eduardo; Paz-y-Miño, Cesar; Sánchez-Rodríguez, Aminael; Perera-Sardiña, Yunier; Perez-Castillo, Yunierkis

    2017-01-01

    Background: In the context of the current drug discovery efforts to find disease modifying therapies for Parkinson´s disease (PD) the current single target strategy has proved inefficient. Consequently, the search for multi-potent agents is attracting more and more attention due to the multiple pathogenetic factors implicated in PD. Multiple evidences points to the dual inhibition of the monoamine oxidase B (MAO-B), as well as adenosine A2A receptor (A2AAR) blockade, as a promising approach to prevent the neurodegeneration involved in PD. Currently, only two chemical scaffolds has been proposed as potential dual MAO-B inhibitors/A2AAR antagonists (caffeine derivatives and benzothiazinones). Methods: In this study, we conduct a series of chemoinformatics analysis in order to evaluate and advance the potential of the chromone nucleus as a MAO-B/A2AAR dual binding scaffold. Results: The information provided by SAR data mining analysis based on network similarity graphs and molecular docking studies support the suitability of the chromone nucleus as a potential MAO-B/A2AAR dual binding scaffold. Additionally, a virtual screening tool based on a group fusion similarity search approach was developed for the prioritization of potential MAO-B/A2AAR dual binder candidates. Among several data fusion schemes evaluated, the MEAN-SIM and MIN-RANK GFSS approaches demonstrated to be efficient virtual screening tools. Then, a combinatorial library potentially enriched with MAO-B/A2AAR dual binding chromone derivatives was assembled and sorted by using the MIN-RANK and then the MEAN-SIM GFSS VS approaches. Conclusion: The information and tools provided in this work represent valuable decision making elements in the search of novel chromone derivatives with a favorable dual binding profile as MAO-B inhibitors and A2AAR antagonists with the potential to act as a disease-modifying therapeutic for Parkinson´s disease. PMID:28093976

  9. Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR).

    PubMed

    Gomez, Sandra; Adalid-Peralta, Laura; Palafox-Fonseca, Hector; Cantu-Robles, Vito Adrian; Soberón, Xavier; Sciutto, Edda; Fragoso, Gladis; Bobes, Raúl J; Laclette, Juan P; Yauner, Luis del Pozo; Ochoa-Leyva, Adrián

    2015-05-19

    Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest.

  10. Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR)

    PubMed Central

    Gomez, Sandra; Adalid-Peralta, Laura; Palafox-Fonseca, Hector; Cantu-Robles, Vito Adrian; Soberón, Xavier; Sciutto, Edda; Fragoso, Gladis; Bobes, Raúl J.; Laclette, Juan P.; Yauner, Luis del Pozo; Ochoa-Leyva, Adrián

    2015-01-01

    Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest. PMID:25989346

  11. Halogen and trace element geochemistry in Mid-Ocean Ridge basalts from the Australian-Antarctic Ridge (AAR)

    NASA Astrophysics Data System (ADS)

    Yang, Y. S.; Seo, J. H.; Park, S. H.; Kim, T.

    2015-12-01

    Australian-Antarctic Ridge (AAR) is an extension of easternmost SE Indian Mid-Ocean Ridge (MOR).We collected volcanic glasses from the "in-axis" of the KR1 and KR2 MOR, and the overlapping zones of the KR1 MOR and the nearby seamounts ("KR1 mixing"). We determined trace and halogen elements in the glasses. Halogen concentrations and its ratios in the glasses are important to understand the mantle metasomatism and volatile recycling. 52 of the collected glasses are "primitive" (higher than 6 wt% MgO), while 3 of them have rather "evolved" composition (MgO wt% of 1.72, 2.95 and 4.15). K2O concentrations and Th/Sc ratios in the glasses show a negative correlation with its MgO concentration. Incompatible element ratios such as La/Sm are rather immobile during a magma differentiation so the ratios are important to understand mantle composition (Hofmann et al. 2003). La/Sm ratios in the glasses are 0.95 ~ 3.28 suggesting that the AAR basalts can be classified into T-MORB and E-MORB (Schilling et al., 1983). La/Sm ratios are well-correlated with incompatible elements such as U, Ba, Nb, and negatively correlated with compatible elements such as Sc, Eu2+, Mg. The AAR glasses contain detectable halogen elements. The "KR1 mixing" glasses in halogen elements are more abundant than "in-axis" the glasses. Cl is the least variable element compared to the other halogens such as Br and I in the AAR. The "KR1 mixing" glasses have the largest variations of Br/Cl ratios compared to the "in-axis" glasses. The Cl/Br and Th/Sc ratios in the "in-axis" glasses and in the "KR1 mixing" glasses show positive and negative correlations, respectively. The Br-rich glasses in the "KR1 mixing" zone might be explained by a recycled Br-rich oceanic slab of paleo-subduction or by a hydrothermal alteration in the AAR. I composition in the glasses does not show a correlation other trace elements. The K/Cl and K/Ti ratios in the AAR glasses are similar to the basalts from the Galapagos Spreading Center

  12. A subaquatic moraine complex in overdeepened Lake Thun (Switzerland) unravelling the deglaciation history of the Aare Glacier

    NASA Astrophysics Data System (ADS)

    Fabbri, S. C.; Buechi, M. W.; Horstmeyer, H.; Hilbe, M.; Hübscher, C.; Schmelzbach, C.; Weiss, B.; Anselmetti, F. S.

    2018-05-01

    To investigate the history of the Aare Glacier and its overdeepened valley, a high-resolution multibeam bathymetric dataset and a 2D multi-channel reflection seismic dataset were acquired on perialpine Lake Thun (Switzerland). The overdeepened basin was formed by a combination of tectonically predefined weak zones and glacial erosion during several glacial cycles. In the deepest region of the basin, top of bedrock lies at ∼200 m below sea level, implying more than 750 m of overdeepening with respect to the current fluvial base level (i.e. lake level). Seismic stratigraphic analysis reveals the evolution of the basin and indicates a subaquatic moraine complex marked by high-amplitude reflections below the outermost edge of a morphologically distinct platform in the southeastern part of the lake. This stack of seven subaquatic terminal moraine crests was created by a fluctuating, "quasi-stagnant" grounded Aare Glacier during its overall recessional phase. Single packages of overridden moraine crests are seismically distuinguishable, which show a transition downstream into prograding clinoforms with foresets at the ice-distal slope. The succession of subaquatic glacial sequences (foresets and adjacent bottomsets) represent one fifth of the entire sedimentary thickness. Exact time constraints concerning the deglacial history of the Aare Glacier are very sparse. However, existing 10Be exposure ages from the accumulation area of the Aare Glacier and radiocarbon ages from a Late-Glacial lake close to the outlet of Lake Thun indicate that the formation of the subaquatic moraine complex and the associated sedimentary infill must have occurred in less than 1000 years, implying high sedimentation rates and rapid disintegration of the glacier. These new data improve our comprehension of the landforms associated with the ice-contact zone in water, the facies architecture of the sub- to proglacial units, the related depositional processes, and thus the retreat mechanisms of

  13. Amino acid racemization analysis (AAR) as a successful tool for dating Holocene coastal sediments: Stratigraphy of a barrier island spit (Southern Sylt/North Sea)

    NASA Astrophysics Data System (ADS)

    Tillmann, Tanja; Ziehe, Daniel

    2014-05-01

    Dating of Holocene sediments in shallow coastal areas of the German North Sea by conventional techniques is commonly problematic. In particular the marine reservoir effect of radiocarbon means that radiocarbon dating cannot be applied to sediments younger than about 400 years. Amino acid racemization dating (AAR) is a viable alternative for dating young sediments. The method is based on the determination of ratios of D and L amino acid enantiomers in organic matrices of biogenic carbonates. In this study we use AAR as a tool for dating Holocene barrier islands sediments. Based on an AAR derived chronological framework we develop a model of barrier spit accretion which describes the interaction between extreme events, fair weather coastal processes and sedimentary development that constrains the major episodes of barrier island evolution. The stratigraphy was defined using ground-penetrating radar (GPR) surveys complemented by sedimentological coring data. The stratigraphy is then conceptualised in a AAR chronostratigraphic framework to define a chronological order and allow the development of a stratigraphic model of the evolution of Southern Sylt. The AAR data provide high temporal resolution and have been used for dating stages of barrier spit accretion. The time lines are marked as storm surge generated erosion unconformities in the stratigraphic profile. Individual shells and shell fragments of Cerastoderma edule, Mya arenaria, Mytilus edulis and Scrobicularia plana have been accumulated by short-term storm events as shell layers associated with the erosion unconformities and have been dated by AAR. Time lines reveal that the barrier spit accretion occurred episodically, and is dependant on the provided rate of sand delivery. The general trend is that sequences young to the. South. The AAR derived time lines have been verified and correlated by historic maps and sea charts. It is apparent that spit enlargement at this site increased significantly during the

  14. Research on Standard and Automatic Judgment of Press-fit Curve of Locomotive Wheel-set Based on AAR Standard

    NASA Astrophysics Data System (ADS)

    Lu, Jun; Xiao, Jun; Gao, Dong Jun; Zong, Shu Yu; Li, Zhu

    2018-03-01

    In the production of the Association of American Railroads (AAR) locomotive wheel-set, the press-fit curve is the most important basis for the reliability of wheel-set assembly. In the past, Most of production enterprises mainly use artificial detection methods to determine the quality of assembly. There are cases of miscarriage of justice appear. For this reason, the research on the standard is carried out. And the automatic judgment of press-fit curve is analysed and designed, so as to provide guidance for the locomotive wheel-set production based on AAR standard.

  15. Fatigue performance of AAR class A railroad wheel steel at ambient and elevated temperatures

    DOT National Transportation Integrated Search

    2005-11-05

    This paper reports on tests to measure the effect of temperature on fatigue performance of railroad wheel steel. Classical stress-life (S-N) curves were developed for AAR Class B wheel steel with specimens removed from the tread areas of an as-forged...

  16. Spatial distribution of quartz recrystallization microstructures across the Aar massif (Swiss Central Alps)

    NASA Astrophysics Data System (ADS)

    Peters, M.; Herwegh, M.

    2012-04-01

    In the Aar massif, main foliation and major deformation structures were developed during NW-SE compression associated with the Alpine orogeny (Steck 1968). To be precise, shearing at the brittle to ductile transition may have initiated at different stages between 22-20 Ma and 14-12 Ma, followed by purely brittle deformation at around 10 Ma (Rolland et al. 2009). In light of the onset of dynamic recrystallization in quartz, Bambauer et al. (2009) defined a quartz recrystallization isograd in the northern part of the Aar massif. To the south, the grain size of recrystallized grains increases due to an increase of metamorphic temperatures from N to S. The aim of the current project is to carry out quantitative analysis on changes of the dynamic and static recrystallization behavior of quartz. Across the Aar massif, two general types of microstructures have to be discriminated: (i) weakly to moderately deformed host rocks and (ii) intensely deformed mylonites to ultramylonites out of high strain shear zones. In (i), volume fraction and size of recrystallized quartz grains increase towards the S showing grain size changes from around 5 µm up to ca. 200 µm. Southern microstructures are characterized by complete recrystallization. In terms of recrystallization processes, a transition from bulging recrystallization in the N to subgrain rotation recrystallization in the S occurs. Such a change in dynamic recrystallization processes combined with a grain size increase points towards reduced differential stresses with increasing temperature. This temperature gradient is also corroborated by a switch in the active glide systems in quartz from basal to rhomb dominated glide. In contrast to the granitic host rocks, the mylonites and ultramylonites (ii) show smaller recrystallized grain sizes due to enhanced strain rates. However, they also reveal a general increase of recrystallized grain sizes from N to S. In the S, microstructures from (i) and (ii) show equidimensional

  17. Adult Attachment Ratings (AAR): an item response theory analysis.

    PubMed

    Pilkonis, Paul A; Kim, Yookyung; Yu, Lan; Morse, Jennifer Q

    2014-01-01

    The Adult Attachment Ratings (AAR) include 3 scales for anxious, ambivalent attachment (excessive dependency, interpersonal ambivalence, and compulsive care-giving), 3 for avoidant attachment (rigid self-control, defensive separation, and emotional detachment), and 1 for secure attachment. The scales include items (ranging from 6-16 in their original form) scored by raters using a 3-point format (0 = absent, 1 = present, and 2 = strongly present) and summed to produce a total score. Item response theory (IRT) analyses were conducted with data from 414 participants recruited from psychiatric outpatient, medical, and community settings to identify the most informative items from each scale. The IRT results allowed us to shorten the scales to 5-item versions that are more precise and easier to rate because of their brevity. In general, the effective range of measurement for the scales was 0 to +2 SDs for each of the attachment constructs; that is, from average to high levels of attachment problems. Evidence for convergent and discriminant validity of the scales was investigated by comparing them with the Experiences of Close Relationships-Revised (ECR-R) scale and the Kobak Attachment Q-sort. The best consensus among self-reports on the ECR-R, informant ratings on the ECR-R, and expert judgments on the Q-sort and the AAR emerged for anxious, ambivalent attachment. Given the good psychometric characteristics of the scale for secure attachment, however, this measure alone might provide a simple alternative to more elaborate procedures for some measurement purposes. Conversion tables are provided for the 7 scales to facilitate transformation from raw scores to IRT-calibrated (theta) scores.

  18. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex Scores in Predicting the Presence of Esophageal Varices in Liver Cirrhosis

    PubMed Central

    Deng, Han; Qi, Xingshun; Guo, Xiaozhong

    2015-01-01

    Abstract Aspartate aminotransferase-to-platelet ratio (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, FI, King, Lok, Forns, and FibroIndex scores may be simple and convenient noninvasive diagnostic tests, because they are based on the regular laboratory tests and demographic data. This study aimed to systematically evaluate their diagnostic accuracy for the prediction of varices in liver cirrhosis. All relevant papers were searched via PubMed, EMBASE, CNKI, and Wanfang databases. The area under the summary receiver operating characteristic curve (AUSROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), and diagnostic odds ratio (DOR) were calculated. Overall, 12, 4, 5, 0, 0, 4, 3, and 1 paper was identified to explore the diagnostic accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex scores, respectively. The AUSROCs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of varices were 0.6774, 0.7275, 0.7755, 0.7885, and 0.7517, respectively; and those for the prediction of large varices were 0.7278, 0.7448, 0.7095, 0.7264, and 0.6530, respectively. The diagnostic threshold effects of FIB-4 and Forns scores for the prediction of varices were statistically significant. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, and Lok scores for the prediction of varices were 0.60/0.67/1.77/0.58/3.13, 0.64/0.63/1.97/0.54/4.18, and 0.74/0.68/2.34/0.40/5.76, respectively. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of large varices were 0.65/0.66/2.15/0.47/4.97, 0.68/0.58/2.07/0.54/3.93, 0.62/0.64/2.02/0.56/3.57, 0.78/0.63/2.09/0.37/5.55, and 0.65/0.61/1.62/0.59/2.75, respectively. APRI, AAR, FIB-4, Lok, and Forns scores had low to moderate diagnostic accuracy in predicting the presence of varices in liver cirrhosis. PMID:26496312

  19. Genotype/phenotype correlations in AARS-related neuropathy in a cohort of patients from the United Kingdom and Ireland.

    PubMed

    Bansagi, Boglarka; Antoniadi, Thalia; Burton-Jones, Sarah; Murphy, Sinead M; McHugh, John; Alexander, Michael; Wells, Richard; Davies, Joanna; Hilton-Jones, David; Lochmüller, Hanns; Chinnery, Patrick; Horvath, Rita

    2015-08-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy with heterogeneous clinical presentation and genetic background. The axonal form (CMT2) is characterised by decreased action potentials indicating primary axonal damage. The underlying pathology involves axonal degeneration which is supposed to be related to axonal protein dysfunction caused by various gene mutations. The overlapping clinical manifestation of CMT2 with distal hereditary motor neuropathy (dHMN) and intermediate CMT causes further diagnostic difficulties. Aminoacyl-tRNA synthetases have been implicated in the pathomechanism of CMT2. They have an essential role in protein translation by attaching amino acids to their cognate tRNAs. To date six families have been reported worldwide with dominant missense alanyl-tRNA synthetase (AARS) mutations leading to clinically heterogeneous axonal neuropathies. The pathomechanism of some variants could be explained by impaired amino acylation activity while other variants implicating an editing defect need to be further investigated. Here, we report a cohort of six additional families originating from the United Kingdom and Ireland with dominant AARS-related neuropathies. The phenotypic manifestation was distal lower limb predominant sensorimotor neuropathy but upper limb impairment with split hand deformity occasionally associated. Nerve conduction studies revealed significant demyelination accompanying the axonal lesion in motor and sensory nerves. Five families have the c.986G>A, p.(Arg329His) variant, further supporting that this is a recurrent loss of function variant. The sixth family, of Irish origin, had a novel missense variant, c.2063A>G, p.(Glu688Gly). We discuss our findings and the associated phenotypic heterogeneity in these families, which expands the clinical spectrum of AARS-related neuropathies.

  20. Use of after action reports (AARs) to promote organizational and systems learning in emergency preparedness.

    PubMed

    Savoia, Elena; Agboola, Foluso; Biddinger, Paul D

    2012-08-01

    Many public health and healthcare organizations use formal knowledge management practices to identify and disseminate the experiences gained over time. The "lessons-learned" approach is one such example of knowledge management practice applied to the wider concept of organizational learning. In the field of emergency preparedness, the lessons-learned approach stands on the assumption that learning from experience improves practice and minimizes avoidable deaths and negative economic and social consequences of disasters. In this project, we performed a structured review of AARs to analyze how lessons learned from the response to real-incidents may be used to maximize knowledge management and quality improvement practices such as the design of public health emergency preparedness (PHEP) exercises. We chose as a source of data the "Lessons Learned Information Sharing (LLIS.gov)" system, a joined program of the U.S. Department of Homeland Security DHS and FEMA that serves as the national, online repository of lessons learned, best practices, and innovative ideas. We identified recurring challenges reported by various states and local public health agencies in the response to different types of incidents. We also strove to identify the limitations of systematic learning that can be achieved due to existing weaknesses in the way AARs are developed.

  1. Use of After Action Reports (AARs) to Promote Organizational and Systems Learning in Emergency Preparedness

    PubMed Central

    Savoia, Elena; Agboola, Foluso; Biddinger, Paul D.

    2012-01-01

    Many public health and healthcare organizations use formal knowledge management practices to identify and disseminate the experiences gained over time. The “lessons-learned” approach is one such example of knowledge management practice applied to the wider concept of organizational learning. In the field of emergency preparedness, the lessons-learned approach stands on the assumption that learning from experience improves practice and minimizes avoidable deaths and negative economic and social consequences of disasters. In this project, we performed a structured review of AARs to analyze how lessons learned from the response to real-incidents may be used to maximize knowledge management and quality improvement practices such as the design of public health emergency preparedness (PHEP) exercises. We chose as a source of data the “Lessons Learned Information Sharing (LLIS.gov)” system, a joined program of the U.S. Department of Homeland Security DHS and FEMA that serves as the national, online repository of lessons learned, best practices, and innovative ideas. We identified recurring challenges reported by various states and local public health agencies in the response to different types of incidents. We also strived to identify the limitations of systematic learning that can be achieved due to existing weaknesses in the way AARs are developed. PMID:23066408

  2. A NASA F/A-18, participating in the Automated Aerial Refueling (AAR) project, flies over the Dryden

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A NASA F/A-18 is participating in the Automated Aerial Refueling (AAR) project. The 300-gallon aerial refueling store seen on the belly of the aircraft carries fuel and a refueling drogue. This aircraft acts as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

  3. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex Scores in Predicting the Presence of Esophageal Varices in Liver Cirrhosis: A Systematic Review and Meta-Analysis.

    PubMed

    Deng, Han; Qi, Xingshun; Guo, Xiaozhong

    2015-10-01

    Aspartate aminotransferase-to-platelet ratio (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, FI, King, Lok, Forns, and FibroIndex scores may be simple and convenient noninvasive diagnostic tests, because they are based on the regular laboratory tests and demographic data. This study aimed to systematically evaluate their diagnostic accuracy for the prediction of varices in liver cirrhosis.All relevant papers were searched via PubMed, EMBASE, CNKI, and Wanfang databases. The area under the summary receiver operating characteristic curve (AUSROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), and diagnostic odds ratio (DOR) were calculated.Overall, 12, 4, 5, 0, 0, 4, 3, and 1 paper was identified to explore the diagnostic accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex scores, respectively. The AUSROCs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of varices were 0.6774, 0.7275, 0.7755, 0.7885, and 0.7517, respectively; and those for the prediction of large varices were 0.7278, 0.7448, 0.7095, 0.7264, and 0.6530, respectively. The diagnostic threshold effects of FIB-4 and Forns scores for the prediction of varices were statistically significant. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, and Lok scores for the prediction of varices were 0.60/0.67/1.77/0.58/3.13, 0.64/0.63/1.97/0.54/4.18, and 0.74/0.68/2.34/0.40/5.76, respectively. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of large varices were 0.65/0.66/2.15/0.47/4.97, 0.68/0.58/2.07/0.54/3.93, 0.62/0.64/2.02/0.56/3.57, 0.78/0.63/2.09/0.37/5.55, and 0.65/0.61/1.62/0.59/2.75, respectively.APRI, AAR, FIB-4, Lok, and Forns scores had low to moderate diagnostic accuracy in predicting the presence of varices in liver cirrhosis.

  4. FibroScan, aspartate aminotransferase and alanine aminotransferase ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the 4 factor (FIB-4), and their combinations in the assessment of liver fibrosis in patients with hepatitis B.

    PubMed

    Ding, Deping; Li, Hongbing; Liu, Ping; Chen, Lingli; Kang, Jian; Zhang, Yinhua; Ma, Deqiang; Chen, Yue; Luo, Jie; Meng, Zhongji

    2015-01-01

    The aim of this study was to assess the effects of FibroScan, aspartate aminotransferase and alanine aminotransferase ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the 4 factor (FIB-4) and their combinations on liver fibrosis in patients with hepatitis B. 406 hospitalized patients with chronic hepatitis B (CHB) and cirrhosis in our hospital were analyzed retrospectively and collected patients clinical indicators, including liver stiffness (LS), AAR, APRI and FIB-4, and then compared the differences of these indicators between CHB group and hepatitis B with cirrhosis group. Receiver operating curve (ROC) was used to evaluate the differentiating capacity of these indicators on CHB and liver cirrhosis. Four indicators related to liver cirrhosis had a statistical significance between two groups (P < 0.01); the under ROC curve areas of LS, AAR, APRI and FIB-4 for differential diagnosis of CHB and liver cirrhosis were 0.866, 0.772, 0.632 and 0.885, respectively. The under ROC curve areas of LS, AAR, APRI and FIB-4 for differential diagnosis of liver cirrhosis at compensatory stage and de-compensatory stage were 0.627, 0.666, 0.795 and 0.820, respectively. LS, AAR, APRI and FIB-4 were good indicators as clinical diagnosis and differential diagnosis on hepatitis B related cirrhosis.

  5. Lake Biel Holocene sediment record before and after the Aare river deviation (1878 AD)

    NASA Astrophysics Data System (ADS)

    Jeannet, Alice; Corella, Juan Pablo; Kremer, Katrina; Girardclos, Stéphanie

    2014-05-01

    Lake sediments are excellent archives of environmental and climate changes as well as human impact on lake- and river-systems. Lake Biel is a medium-sized peri-alpine lake in Switzerland, with a maximum depth of 74 m, and lies at an altitude of 429 m a.s.l. Lake Biel, which formed during the Pleistocene by glacial erosion, is part of the Aare river system. Our study focuses on the south-west part of the lake basin where the lake sedimentation was originally (i.e. naturally) mainly controlled by autochthonous sedimentation. This area is currently under a strong influence of water and sediment input from this river catchment since the Aare river deviation through the Hagneck canal in 1878. A 10.05 m long composite sediment sequence, cored from a 52 m water depth in September 2011, was built from two long cores retrieved with the ETH Zurich/Eawag Uwitec system. A radiocarbon age model indicates that the retrieved sedimentary sequence spans the last 7500 years. The upper sediments were correlated to previous short core radionuclide stratigraphy for the 1.5 m upper part (Thevenon et al., 2013). Magnetic susceptibility and density were measured by Geotek MultiSensor Core Logger at 0.5 cm resolution. Granulometry was measured with a CILAS grain sizer every 10 cm, and X-ray fluorescence (XRF) was carried out using an Avaatech core scanner at 1-cm resolution. This technique provides semi-quantitative information of the sediment elemental composition and shows how runoff and river input (Ti, Al, Si) or redox conditions (Fe/Mn) vary through time. Lake Biel sediment record suggests marked environmental changes with runoff decrease linked to climate and vegetation change during Atlantic chronobiozone, as well as a complex climate-human impact during the 'La Tène' and Roman cultural times. The most prominent recorded feature is the 10-times increase of sediment rate that occurred after the Aare river deviation through the Hagneck canal into Lake Biel in 1878. This artificial

  6. This NASA Dryden F/A-18 is participating in the Automated Aerial Refueling (AAR) project. F/A-18 (No

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A NASA Dryden F/A-18 is participating in the Automated Aerial Refueling (AAR) project. F/A-18 (No. 847) is acting as an in-flight refueling tanker in the study to develop analytical models for an automated aerial refueling system for unmanned vehicles. A 300-gallon aerodynamic pod containing air-refueling equipment is seen beneath the fuselage. The hose and refueling basket are extended during an assessment of their dynamics on the F/A-18A.

  7. Structural modeling of tissue-specific mitochondrial alanyl-tRNA synthetase (AARS2) defects predicts differential effects on aminoacylation

    PubMed Central

    Euro, Liliya; Konovalova, Svetlana; Asin-Cayuela, Jorge; Tulinius, Már; Griffin, Helen; Horvath, Rita; Taylor, Robert W.; Chinnery, Patrick F.; Schara, Ulrike; Thorburn, David R.; Suomalainen, Anu; Chihade, Joseph; Tyynismaa, Henna

    2015-01-01

    The accuracy of mitochondrial protein synthesis is dependent on the coordinated action of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases (mtARSs) and the mitochondrial DNA-encoded tRNAs. The recent advances in whole-exome sequencing have revealed the importance of the mtARS proteins for mitochondrial pathophysiology since nearly every nuclear gene for mtARS (out of 19) is now recognized as a disease gene for mitochondrial disease. Typically, defects in each mtARS have been identified in one tissue-specific disease, most commonly affecting the brain, or in one syndrome. However, mutations in the AARS2 gene for mitochondrial alanyl-tRNA synthetase (mtAlaRS) have been reported both in patients with infantile-onset cardiomyopathy and in patients with childhood to adulthood-onset leukoencephalopathy. We present here an investigation of the effects of the described mutations on the structure of the synthetase, in an effort to understand the tissue-specific outcomes of the different mutations. The mtAlaRS differs from the other mtARSs because in addition to the aminoacylation domain, it has a conserved editing domain for deacylating tRNAs that have been mischarged with incorrect amino acids. We show that the cardiomyopathy phenotype results from a single allele, causing an amino acid change R592W in the editing domain of AARS2, whereas the leukodystrophy mutations are located in other domains of the synthetase. Nevertheless, our structural analysis predicts that all mutations reduce the aminoacylation activity of the synthetase, because all mtAlaRS domains contribute to tRNA binding for aminoacylation. According to our model, the cardiomyopathy mutations severely compromise aminoacylation whereas partial activity is retained by the mutation combinations found in the leukodystrophy patients. These predictions provide a hypothesis for the molecular basis of the distinct tissue-specific phenotypic outcomes. PMID:25705216

  8. Estimating the gas transfer velocity: a prerequisite for more accurate and higher resolution GHG fluxes (lower Aare River, Switzerland)

    NASA Astrophysics Data System (ADS)

    Sollberger, S.; Perez, K.; Schubert, C. J.; Eugster, W.; Wehrli, B.; Del Sontro, T.

    2013-12-01

    Currently, carbon dioxide (CO2) and methane (CH4) emissions from lakes, reservoirs and rivers are readily investigated due to the global warming potential of those gases and the role these inland waters play in the carbon cycle. However, there is a lack of high spatiotemporally-resolved emission estimates, and how to accurately assess the gas transfer velocity (K) remains controversial. In anthropogenically-impacted systems where run-of-river reservoirs disrupt the flow of sediments by increasing the erosion and load accumulation patterns, the resulting production of carbonic greenhouse gases (GH-C) is likely to be enhanced. The GH-C flux is thus counteracting the terrestrial carbon sink in these environments that act as net carbon emitters. The aim of this project was to determine the GH-C emissions from a medium-sized river heavily impacted by several impoundments and channelization through a densely-populated region of Switzerland. Estimating gas emission from rivers is not trivial and recently several models have been put forth to do so; therefore a second goal of this project was to compare the river emission models available with direct measurements. Finally, we further validated the modeled fluxes by using a combined approach with water sampling, chamber measurements, and highly temporal GH-C monitoring using an equilibrator. We conducted monthly surveys along the 120 km of the lower Aare River where we sampled for dissolved CH4 (';manual' sampling) at a 5-km sampling resolution, and measured gas emissions directly with chambers over a 35 km section. We calculated fluxes (F) via the boundary layer equation (F=K×(Cw-Ceq)) that uses the water-air GH-C concentration (C) gradient (Cw-Ceq) and K, which is the most sensitive parameter. K was estimated using 11 different models found in the literature with varying dependencies on: river hydrology (n=7), wind (2), heat exchange (1), and river width (1). We found that chamber fluxes were always higher than boundary

  9. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, and King Scores for Diagnosis of Esophageal Varices in Liver Cirrhosis: A Retrospective Study.

    PubMed

    Deng, Han; Qi, Xingshun; Peng, Ying; Li, Jing; Li, Hongyu; Zhang, Yongguo; Liu, Xu; Sun, Xiaolin; Guo, Xiaozhong

    2015-12-20

    BACKGROUND Aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, fibrosis index (FI), and King scores might be alternatives to the use of upper gastrointestinal endoscopy for the diagnosis of esophageal varices (EVs) in liver cirrhosis. This study aimed to evaluate their diagnostic accuracy in predicting the presence and severity of EVs in liver cirrhosis. MATERIAL AND METHODS All patients who were consecutively admitted to our hospital and underwent upper gastrointestinal endoscopy between January 2012 and June 2014 were eligible for this retrospective study. Areas under curve (AUCs) were calculated. Subgroup analyses were performed according to the history of upper gastrointestinal bleeding (UGIB) and splenectomy. RESULTS A total of 650 patients with liver cirrhosis were included, and 81.4% of them had moderate-severe EVs. In the overall analysis, the AUCs of these non-invasive scores for predicting moderate-severe EVs and presence of any EVs were 0.506-0.6 and 0.539-0.612, respectively. In the subgroup analysis of patients without UGIB, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.601-0.664 and 0.596-0.662, respectively. In the subgroup analysis of patients without UGIB or splenectomy, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.627-0.69 and 0.607-0.692, respectively. CONCLUSIONS APRI, AAR, FIB-4, FI, and King scores had modest diagnostic accuracy of EVs in liver cirrhosis. They might not be able to replace the utility of upper gastrointestinal endoscopy for the diagnosis of EVs in liver cirrhosis.

  10. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, and King Scores for Diagnosis of Esophageal Varices in Liver Cirrhosis: A Retrospective Study

    PubMed Central

    Deng, Han; Qi, Xingshun; Peng, Ying; Li, Jing; Li, Hongyu; Zhang, Yongguo; Liu, Xu; Sun, Xiaolin; Guo, Xiaozhong

    2015-01-01

    Background Aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, fibrosis index (FI), and King scores might be alternatives to the use of upper gastrointestinal endoscopy for the diagnosis of esophageal varices (EVs) in liver cirrhosis. This study aimed to evaluate their diagnostic accuracy in predicting the presence and severity of EVs in liver cirrhosis. Material/Methods All patients who were consecutively admitted to our hospital and underwent upper gastrointestinal endoscopy between January 2012 and June 2014 were eligible for this retrospective study. Areas under curve (AUCs) were calculated. Subgroup analyses were performed according to the history of upper gastrointestinal bleeding (UGIB) and splenectomy. Results A total of 650 patients with liver cirrhosis were included, and 81.4% of them had moderate-severe EVs. In the overall analysis, the AUCs of these non-invasive scores for predicting moderate-severe EVs and presence of any EVs were 0.506–0.6 and 0.539–0.612, respectively. In the subgroup analysis of patients without UGIB, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.601–0.664 and 0.596–0.662, respectively. In the subgroup analysis of patients without UGIB or splenectomy, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.627–0.69 and 0.607–0.692, respectively. Conclusions APRI, AAR, FIB-4, FI, and King scores had modest diagnostic accuracy of EVs in liver cirrhosis. They might not be able to replace the utility of upper gastrointestinal endoscopy for the diagnosis of EVs in liver cirrhosis. PMID:26687574

  11. Lgr4 promotes prostate tumorigenesis through the Jmjd2a/AR signaling pathway.

    PubMed

    Zhang, Jianwei; Li, Qi; Zhang, Shaojin; Xu, Quanquan; Wang, Tianen

    2016-11-15

    Lgr4 (leucine-rich repeat domain containing G protein-coupled receptor 4) is implicated in the transcriptional regulation of multiple histone demethylases in the progression of diverse cancers, but there are few reports concerning the molecular mechanism by which Lgr4 regulates histone demethylase activation in prostate cancer (PCa) progression. As Jmjd2a is a histone demethylase, in the current study, we investigated the relationship between interaction Lgr4 with Jmjd 2a and Jmjd2a/androgen receptor (AR) signaling pathway in PCa progression. Firstly, Lgr4 was overexpressed by transfecting pcDNA3.1(+)/Lgr4 plasmids into PCa (LNCaP and PC-3) cell lines. Next, we found that Lgr4 overexpression promoted Jmjd2a mRNA expression, reduced cell apoptosis and arrested cell cycle in the S phase, these effects were reversed by Jmjd2a silencing. Moreover, Lgr4 overexpression markedly elevated AR levels and its interaction with Jmjd2a, which was tested by co-immunoprecipitation and luciferase reporter assays. Furthermore, interaction AR with PSA promoter (containing an AR response element) was obviously improved by Lgr4 overexpression, and PSA silencing reduced Lgr4-induced cell apoptosis and cell cycle arrest in PCa cells. Taken together, Lgr4 may be a novel tumor marker providing new mechanistic insights into PCa progression. Lgr4 activates Jmjd2a/AR signaling pathway to promote interaction AR with PSA promoter, causing reduction of PCa apoptosis and cell cycle arrest. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Quantitative assessment of alkali-reactive aggregate mineral content through XRD using polished sections as a supplementary tool to RILEM AAR-1 (petrographic method)

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

    Castro, Nelia, E-mail: nelia.castro@ntnu.no; Sorensen, Bjorn E.; Broekmans, Maarten A.T.M.

    The mineral content of 5 aggregate samples from 4 different countries, including reactive and non-reactive aggregate types, was assessed quantitatively by X-ray diffraction (XRD) using polished sections. Additionally, electron probe microanalyzer (EPMA) mapping and cathodoluminescence (CL) were used to characterize the opal-CT identified in one of the aggregate samples. Critical review of results from polished sections against traditionally powdered specimen has demonstrated that for fine-grained rocks without preferred orientation the assessment of mineral content by XRD using polished sections may represent an advantage over traditional powder specimens. Comparison of data on mineral content and silica speciation with expansion data frommore » PARTNER project confirmed that the presence of opal-CT plays an important role in the reactivity of one of the studied aggregates. Used as a complementary tool to RILEM AAR-1, the methodology suggested in this paper has the potential to improve the strength of the petrographic method.« less

  13. The Incidence, Classification, and Management of Acute Adverse Reactions to the Low-Osmolar Iodinated Contrast Media Isovue and Ultravist in Contrast-Enhanced Computed Tomography Scanning.

    PubMed

    Zhang, Bin; Dong, Yuhao; Liang, Long; Lian, Zhouyang; Liu, Jing; Luo, Xiaoning; Chen, Wenbo; Li, Xinyu; Liang, Changhong; Zhang, Shuixing

    2016-03-01

    Some epidemiologic surveillance studies have recorded adverse drug reactions to radiocontrast agents. We aimed to investigate the incidence and management of acute adverse reactions (AARs) to Ultravist-370 and Isovue-370 in patients who underwent contrast-enhanced computed tomography (CT) scanning.Data from 137,473 patients were analyzed. They had undergone enhanced CT scanning with intravenous injection of Ultravist-370 or Isovue-370 during the period of January 1, 2006 to December 31, 2012 in our hospital. We investigated and classified AARs according to the American College of Radiology and the Chinese Society of Radiology (CSR) guidelines for iodinated contrast media. We analyzed risk factors for AARs and compared the AARs induced by Ultravist-370 and Isovue-370.Four hundred and twenty-eight (0.31%) patients experienced AARs, which included 330 (0.24%) patients with mild AARs, 82 (0.06%) patients with moderate AARs, and 16 (0.01%) patients with severe AARs (including 3 cases of cardiac arrest and one case of death). The incidence of AARs was higher with Ultravist-370 than with Isovue-370 (0.38% vs 0.24%, P < 0.001), but only for mild AARs (0.32% vs 0.16%, P < 0.001). Analyses on risk factors indicated that female patients (n = 221, 0.43%, P < 0.001), emergency patients (n = 11, 0.51%, P < 0.001), elderly patients aged 50 to 60 years (n = 135, 0.43%, P < 0.001), and patients who underwent coronary computed tomography angiography (CTA) (n = 55, 0.51%, P < 0.001) had a higher risk of AARs. Cutaneous manifestations (50.52%)-especially rash (59.74%)-were the most frequent mild AARs. Cardiovascular manifestations accounted for most moderate and severe AARs (62.91% and 48.28%, respectively). After proper management, the symptoms and signs of 96.5% of the AARs resolved within 24 hours without sequelae.Ultravist-370 and Isovue-370 are safe for patients undergoing enhanced CT scanning. The incidence of AARs is higher with Ultravist

  14. The Incidence, Classification, and Management of Acute Adverse Reactions to the Low-Osmolar Iodinated Contrast Media Isovue and Ultravist in Contrast-Enhanced Computed Tomography Scanning

    PubMed Central

    Zhang, Bin; Dong, Yuhao; Liang, Long; Lian, Zhouyang; Liu, Jing; Luo, Xiaoning; Chen, Wenbo; Li, Xinyu; Liang, Changhong; Zhang, Shuixing

    2016-01-01

    Abstract Some epidemiologic surveillance studies have recorded adverse drug reactions to radiocontrast agents. We aimed to investigate the incidence and management of acute adverse reactions (AARs) to Ultravist-370 and Isovue-370 in patients who underwent contrast-enhanced computed tomography (CT) scanning. Data from 137,473 patients were analyzed. They had undergone enhanced CT scanning with intravenous injection of Ultravist-370 or Isovue-370 during the period of January 1, 2006 to December 31, 2012 in our hospital. We investigated and classified AARs according to the American College of Radiology and the Chinese Society of Radiology (CSR) guidelines for iodinated contrast media. We analyzed risk factors for AARs and compared the AARs induced by Ultravist-370 and Isovue-370. Four hundred and twenty-eight (0.31%) patients experienced AARs, which included 330 (0.24%) patients with mild AARs, 82 (0.06%) patients with moderate AARs, and 16 (0.01%) patients with severe AARs (including 3 cases of cardiac arrest and one case of death). The incidence of AARs was higher with Ultravist-370 than with Isovue-370 (0.38% vs 0.24%, P < 0.001), but only for mild AARs (0.32% vs 0.16%, P < 0.001). Analyses on risk factors indicated that female patients (n = 221, 0.43%, P < 0.001), emergency patients (n = 11, 0.51%, P < 0.001), elderly patients aged 50 to 60 years (n = 135, 0.43%, P < 0.001), and patients who underwent coronary computed tomography angiography (CTA) (n = 55, 0.51%, P < 0.001) had a higher risk of AARs. Cutaneous manifestations (50.52%)—especially rash (59.74%)—were the most frequent mild AARs. Cardiovascular manifestations accounted for most moderate and severe AARs (62.91% and 48.28%, respectively). After proper management, the symptoms and signs of 96.5% of the AARs resolved within 24 hours without sequelae. Ultravist-370 and Isovue-370 are safe for patients undergoing enhanced CT scanning. The incidence of AARs is

  15. The adenosine A2A receptor — Myocardial protectant and coronary target in endotoxemia

    PubMed Central

    Reichelt, Melissa E.; Ashton, Kevin J.; Tan, Xing Lin; Mustafa, S. Jamal; Ledent, Catherine; Delbridge, Lea M.D.; Hofmann, Polly A.; Headrick, John P.; Morrison, R. Ray

    2013-01-01

    Background Cardiac injury and dysfunction are contributors to disease progression and mortality in sepsis. This study evaluated the cardiovascular role of intrinsic A2A adenosine receptor (A2AAR) activity during lipopolysaccharide (LPS)-induced inflammation. Methods We assessed the impact of 24 h of LPS challenge (20 mg/kg, IP) on cardiac injury, coronary function and inflammatory mediator levels in Wild-Type (WT) mice and mice lacking functional A2AARs (A2AAR KO). Results Cardiac injury was evident in LPS-treated WTs, with ∼7-fold elevation in serum cardiac troponin I (cTnI), and significant ventricular and coronary dysfunction. Absence of A2AARs increased LPS-provoked cTnI release at 24 h by 3-fold without additional demise of contraction function. Importantly, A2AAR deletion per se emulated detrimental effects of LPS on coronary function, and LPS was without effect in coronary vessels lacking A2AARs. Effects of A2AAR KO were independent of major shifts in circulating C-reactive protein (CRP) and haptoglobin. Cytokine responses were largely insensitive to A2AAR deletion; substantial LPS-induced elevations (up to 100-fold) in IFN-γ and IL-10 were unaltered in A2AAR KO mice, as were levels of IL-4 and TNF-α. However, late elevations in IL-2 and IL-5 were differentially modulated by A2AAR KO (IL-2 reduced, IL-5 increased). Data demonstrate that in the context of LPS-triggered cardiac and coronary injury, A2AAR activity protects myocardial viability without modifying contractile dysfunction, and selectively modulates cytokine (IL-2, IL-5) release. A2AARs also appear to be targeted by LPS in the coronary vasculature. Conclusions These experimental data suggest that preservation of A2AAR functionality might provide therapeutic benefit in human sepsis. PMID:22192288

  16. Cross-talk from β-Adrenergic Receptors Modulates α2A-Adrenergic Receptor Endocytosis in Sympathetic Neurons via Protein Kinase A and Spinophilin*

    PubMed Central

    Cottingham, Christopher; Lu, Roujian; Jiao, Kai; Wang, Qin

    2013-01-01

    Inter-regulation of adrenergic receptors (ARs) via cross-talk is a long appreciated but mechanistically unclear physiological phenomenon. Evidence from the AR literature and our own extensive studies on regulation of α2AARs by the scaffolding protein spinophilin have illuminated a potential novel mechanism for cross-talk from β to α2ARs. In the present study, we have characterized a mode of endogenous AR cross-talk in native adrenergic neurons whereby canonical βAR-mediated signaling modulates spinophilin-regulated α2AAR endocytosis through PKA. Our findings demonstrate that co-activation of β and α2AARs, either by application of endogenous agonist or by simultaneous stimulation with distinct selective agonists, results in acceleration of endogenous α2AAR endocytosis in native neurons. We show that receptor-independent PKA activation by forskolin is sufficient to accelerate α2AAR endocytosis and that α2AAR stimulation alone drives accelerated endocytosis in spinophilin-null neurons. Endocytic response acceleration by β/α2AAR co-activation is blocked by PKA inhibition and lost in spinophilin-null neurons, consistent with our previous finding that spinophilin is a substrate for phosphorylation by PKA that disrupts its interaction with α2AARs. Importantly, we show that α2AR agonist-mediated α2AAR/spinophilin interaction is blocked by βAR co-activation in a PKA-dependent fashion. We therefore propose a novel mechanism for cross-talk from β to α2ARs, whereby canonical βAR-mediated signaling coupled to PKA activation results in phosphorylation of spinophilin, disrupting its interaction with α2AARs and accelerating α2AAR endocytic responses. This mechanism of cross-talk has significant implications for endogenous adrenergic physiology and for therapeutic targeting of β and α2AARs. PMID:23965992

  17. Aspartic acid racemisation in purified elastin from arteries as basis for age estimation.

    PubMed

    Dobberstein, R C; Tung, S-M; Ritz-Timme, S

    2010-07-01

    Aspartic acid racemisation (AAR) results in an age-dependent accumulation of D: -aspartic acid in durable human proteins and can be used as a basis for age estimation. Routinely, age estimation based on AAR is performed by analysis of dentine. However, in forensic practise, teeth are not always available. Non-dental tissues for age estimation may be suitable for age estimation based on AAR if they contain durable proteins that can be purified and analysed. Elastin is such a durable protein. To clarify if purified elastin from arteries is a suitable sample for biochemical age estimation, AAR was determined in purified elastin from arteries from individuals of known age (n = 68 individuals, including n = 15 putrefied corpses), considering the influence of different stages of atherosclerosis and putrefaction on the AAR values. AAR was found to increase with age. The relationship between AAR and age was good enough to serve as basis for age estimation, but worse than known from dentinal proteins. Intravital and post-mortem degradation of elastin may have a moderate effect on the AAR values. Age estimation based on AAR in purified elastin from arteries may be a valuable additional tool in the identification of unidentified cadavers, especially in cases where other methods cannot be applied (e.g., no available teeth and body parts).

  18. Differential Occurrence of Interactions and Interaction Domains in Proteins Containing Homopolymeric Amino Acid Repeats

    PubMed Central

    Pelassa, Ilaria; Fiumara, Ferdinando

    2015-01-01

    Homopolymeric amino acids repeats (AARs), which are widespread in proteomes, have often been viewed simply as spacers between protein domains, or even as “junk” sequences with no obvious function but with a potential to cause harm upon expansion as in genetic diseases associated with polyglutamine or polyalanine expansions, including Huntington disease and cleidocranial dysplasia. A growing body of evidence indicates however that at least some AARs can form organized, functional protein structures, and can regulate protein function. In particular, certain AARs can mediate protein-protein interactions, either through homotypic AAR-AAR contacts or through heterotypic contacts with other protein domains. It is still unclear however, whether AARs may have a generalized, proteome-wide role in shaping protein-protein interaction networks. Therefore, we have undertaken here a bioinformatics screening of the human proteome and interactome in search of quantitative evidence of such a role. We first identified the sets of proteins that contain repeats of any one of the 20 amino acids, as well as control sets of proteins chosen at random in the proteome. We then analyzed the connectivity between the proteins of the AAR-containing protein sets and we compared it with that observed in the corresponding control networks. We find evidence for different degrees of connectivity in the different AAR-containing protein networks. Indeed, networks of proteins containing polyglutamine, polyglutamate, polyproline, and other AARs show significantly increased levels of connectivity, whereas networks containing polyleucine and other hydrophobic repeats show lower degrees of connectivity. Furthermore, we observed that numerous protein-protein, -nucleic acid, and -lipid interaction domains are significantly enriched in specific AAR protein groups. These findings support the notion of a generalized, combinatorial role of AARs, together with conventional protein interaction domains, in

  19. Calibration of amino acid racemization (AAR) kinetics in United States mid-Atlantic Coastal Plain Quaternary mollusks using 87Sr/ 86Sr analyses: Evaluation of kinetic models and estimation of regional Late Pleistocene temperature history

    USGS Publications Warehouse

    Wehmiller, J.F.; Harris, W.B.; Boutin, B.S.; Farrell, K.M.

    2012-01-01

    The use of amino acid racemization (AAR) for estimating ages of Quaternary fossils usually requires a combination of kinetic and effective temperature modeling or independent age calibration of analyzed samples. Because of limited availability of calibration samples, age estimates are often based on model extrapolations from single calibration points over wide ranges of D/L values. Here we present paired AAR and 87Sr/ 86Sr results for Pleistocene mollusks from the North Carolina Coastal Plain, USA. 87Sr/ 86Sr age estimates, derived from the lookup table of McArthur et al. [McArthur, J.M., Howarth, R.J., Bailey, T.R., 2001. Strontium isotopic stratigraphy: LOWESS version 3: best fit to the marine Sr-isotopic curve for 0-509 Ma and accompanying Look-up table for deriving numerical age. Journal of Geology 109, 155-169], provide independent age calibration over the full range of amino acid D/L values, thereby allowing comparisons of alternative kinetic models for seven amino acids. The often-used parabolic kinetic model is found to be insufficient to explain the pattern of racemization, although the kinetic pathways for valine racemization and isoleucine epimerization can be closely approximated with this function. Logarithmic and power law regressions more accurately represent the racemization pathways for all amino acids. The reliability of a non-linear model for leucine racemization, developed and refined over the past 20 years, is confirmed by the 87Sr/ 86Sr age results. This age model indicates that the subsurface record (up to 80m thick) of the North Carolina Coastal Plain spans the entire Quaternary, back to ???2.5Ma. The calibrated kinetics derived from this age model yield an estimate of the effective temperature for the study region of 11??2??C., from which we estimate full glacial (Last Glacial Maximum - LGM) temperatures for the region on the order of 7-10??C cooler than present. These temperatures compare favorably with independent paleoclimate information

  20. Interdependence, Reflexivity, Fidelity, Impedance Matching, and the Evolution of Genetic Coding

    PubMed Central

    Carter, Charles W; Wills, Peter R

    2018-01-01

    Abstract Genetic coding is generally thought to have required ribozymes whose functions were taken over by polypeptide aminoacyl-tRNA synthetases (aaRS). Two discoveries about aaRS and their interactions with tRNA substrates now furnish a unifying rationale for the opposite conclusion: that the key processes of the Central Dogma of molecular biology emerged simultaneously and naturally from simple origins in a peptide•RNA partnership, eliminating the epistemological utility of a prior RNA world. First, the two aaRS classes likely arose from opposite strands of the same ancestral gene, implying a simple genetic alphabet. The resulting inversion symmetries in aaRS structural biology would have stabilized the initial and subsequent differentiation of coding specificities, rapidly promoting diversity in the proteome. Second, amino acid physical chemistry maps onto tRNA identity elements, establishing reflexive, nanoenvironmental sensing in protein aaRS. Bootstrapping of increasingly detailed coding is thus intrinsic to polypeptide aaRS, but impossible in an RNA world. These notions underline the following concepts that contradict gradual replacement of ribozymal aaRS by polypeptide aaRS: 1) aaRS enzymes must be interdependent; 2) reflexivity intrinsic to polypeptide aaRS production dynamics promotes bootstrapping; 3) takeover of RNA-catalyzed aminoacylation by enzymes will necessarily degrade specificity; and 4) the Central Dogma’s emergence is most probable when replication and translation error rates remain comparable. These characteristics are necessary and sufficient for the essentially de novo emergence of a coupled gene–replicase–translatase system of genetic coding that would have continuously preserved the functional meaning of genetically encoded protein genes whose phylogenetic relationships match those observed today. PMID:29077934

  1. Isoproterenol Acts as a Biased Agonist of the Alpha-1A-Adrenoceptor that Selectively Activates the MAPK/ERK Pathway

    PubMed Central

    Copik, Alicja. J.; Baldys, Aleksander; Nguyen, Khanh; Sahdeo, Sunil; Ho, Hoangdung; Kosaka, Alan; Dietrich, Paul J.; Fitch, Bill; Raymond, John R.; Ford, Anthony P. D. W.; Button, Donald; Milla, Marcos E.

    2015-01-01

    The α1A-AR is thought to couple predominantly to the Gαq/PLC pathway and lead to phosphoinositide hydrolysis and calcium mobilization, although certain agonists acting at this receptor have been reported to trigger activation of arachidonic acid formation and MAPK pathways. For several G protein-coupled receptors (GPCRs) agonists can manifest a bias for activation of particular effector signaling output, i.e. not all agonists of a given GPCR generate responses through utilization of the same signaling cascade(s). Previous work with Gαq coupling-defective variants of α1A-AR, as well as a combination of Ca2+ channel blockers, uncovered cross-talk between α1A-AR and β2-AR that leads to potentiation of a Gαq-independent signaling cascade in response to α1A-AR activation. We hypothesized that molecules exist that act as biased agonists to selectively activate this pathway. In this report, isoproterenol (Iso), typically viewed as β-AR-selective agonist, was examined with respect to activation of α1A-AR. α1A-AR selective antagonists were used to specifically block Iso evoked signaling in different cellular backgrounds and confirm its action at α1A-AR. Iso induced signaling at α1A-AR was further interrogated by probing steps along the Gαq /PLC, Gαs and MAPK/ERK pathways. In HEK-293/EBNA cells transiently transduced with α1A-AR, and CHO_α1A-AR stable cells, Iso evoked low potency ERK activity as well as Ca2+ mobilization that could be blocked by α1A-AR selective antagonists. The kinetics of Iso induced Ca2+ transients differed from typical Gαq- mediated Ca2+ mobilization, lacking both the fast IP3R mediated response and the sustained phase of Ca2+ re-entry. Moreover, no inositol phosphate (IP) accumulation could be detected in either cell line after stimulation with Iso, but activation was accompanied by receptor internalization. Data are presented that indicate that Iso represents a novel type of α1A-AR partial agonist with signaling bias toward MAPK

  2. Geophysical Investigation of Upper Mantle Anomalies of the Australian-Antarctic Ridge

    NASA Astrophysics Data System (ADS)

    Park, S. H.; Choi, H.; Kim, S. S.; Lin, J.

    2017-12-01

    Australian-Antarctic Ridge (AAR) is situated between the Pacific-Antarctic Ridge (PAR) and Southeast Indian Ridge (SEIR), extending eastward from the Australian-Antarctic Discordance (AAD). Much of the AAR has been remained uncharted until 2011 because of its remoteness and harsh weather conditions. Since 2011, four multidisciplinary expeditions initiated by the Korea Polar Research Institute (KOPRI) have surveyed the little-explored eastern ends of the AAR and investigated the tectonics, geochemistry, and hydrothermal activity of this intermediate spreading system. Recent isotope studies using the new basalt samples from the AAR have led to the new hypothesis of the Southern Ocean mantle domain (SOM), which may have originated from the super-plume activity associated with the Gondwana break-up. In this study, we characterize the geophysics of the Southern Ocean mantle using the newly acquired shipboard bathymetry and available geophysical datasets. First, we computed residual mantle Bouguer gravity anomalies (RMBA), gravity-derived crustal thickness, and residual topography along the AAR in order to obtain a geological proxy for regional variations in magma supply. The results of these analyses revealed that the southern flank of the AAR is associated with shallower seafloor, more negative RMBA, thicker crust, and/or less dense mantle in comparison to the conjugate northern flank. Furthermore, this north-south asymmetry becomes more prominent toward the central ridge segments of the AAR. Interestingly, the along-axis depths of the entire AAR are significantly shallower than the neighboring ridge systems and the global ridges of intermediate spreading rates. Such shallow depths are also correlated with regional negative geoid anomalies. Furthermore, recent mantle tomography models consistently showed that the upper mantle (< 250 km) below the AAR has low S-wave velocities, suggesting that it may be hotter than the nearby ridges. Such regional-scale anomalies of the

  3. 75 FR 13775 - Agency Information Collection Activities: Proposed Collection; Comment Request, 1660-NEW...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-23

    ... Security Exercise and Evaluation Program (HSEEP) After Action Report (AAR) Improvement Plan (IP) AGENCY... (HSEEP) After Action Report (AAR) Improvement Plan (IP). SUMMARY: The Federal Emergency Management Agency... (HSEEP) After Action Report (AAR) Improvement Plan (IP). DATES: Comments must be submitted on or before...

  4. 49 CFR 179.5 - Certificate of construction.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment, and car fully conforms to all... Executive Director—Tank Car Safety, AAR. (c) If the owner elects to furnish service equipment, the owner shall furnish the Executive Director—Tank Car Safety, AAR, a report in prescribed form, certifying that...

  5. 49 CFR 179.5 - Certificate of construction.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment, and car fully conforms to all... Executive Director—Tank Car Safety, AAR. (c) If the owner elects to furnish service equipment, the owner shall furnish the Executive Director—Tank Car Safety, AAR, a report in prescribed form, certifying that...

  6. 49 CFR 179.5 - Certificate of construction.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment, and car fully conforms to all... Executive Director—Tank Car Safety, AAR. (c) If the owner elects to furnish service equipment, the owner shall furnish the Executive Director—Tank Car Safety, AAR, a report in prescribed form, certifying that...

  7. 49 CFR 179.5 - Certificate of construction.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment, and car fully conforms to all... Executive Director—Tank Car Safety, AAR. (c) If the owner elects to furnish service equipment, the owner shall furnish the Executive Director—Tank Car Safety, AAR, a report in prescribed form, certifying that...

  8. 49 CFR 179.5 - Certificate of construction.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... to the owner and the Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment... each series when submitted to the Executive Director—Tank Car Safety, AAR. (c) If the owner elects to furnish service equipment, the owner shall furnish the Executive Director—Tank Car Safety, AAR, a report...

  9. 50th Annual Fuze Conference. Session 1 and 2

    DTIC Science & Technology

    2006-05-11

    PROGRAM OFFICE AMSRD-AAR-AIJ J. Goldman X6060 STRATEGIC MGT OFFICE AMSRD-AAR-EMS D. Denery X6081 KNOWLEDGE MANAGEMENT OFFICE AMSRD-AAR-EMK G. Albinson...Tail-Mounted Configuration (MK-82 Demo) UHF to L-Band Pulse Doppler Radar Using Low Cost COTS Components Nose and Tail Mount Configurations Only

  10. Free-flying dynamics and control of an astronaut assistant robot based on fuzzy sliding mode algorithm

    NASA Astrophysics Data System (ADS)

    Gao, Qing; Liu, Jinguo; Tian, Tongtong; Li, Yangmin

    2017-09-01

    Space robots can perform some tasks in harsh environment as assistants of astronauts or substitutions of astronauts. Taking the limited working time and the arduous task of the astronauts in the space station into account, an astronaut assistant robot (AAR-2) applied in the space station is proposed and designed in this paper. The AAR-2 is achieved with some improvements on the basis of AAR-1 which was designed before. It can exploit its position and attitude sensors and control system to free flight or hover in the space cabin. And it also has a definite environmental awareness and artificial intelligence to complete some specified tasks under the control of astronauts or autonomously. In this paper, it mainly analyzes and controls the 6-DOF motion of the AAR-2. Firstly, the system configuration of AAR-2 is specifically described, and the movement principles are analyzed. Secondly, according to the physical model of the AAR-2, the Newton - Euler equation is applied in the preparation of space dynamics model of 6-DOF motion. Then, according to the mathematical model's characteristics which are nonlinear and strong coupling, a dual closed loop position and attitude controller based on fuzzy sliding mode control is proposed and designed. Finally, simulation experiments are appropriate to provide for AAR-2 control system by using Matlab/Simulink. From the simulation results it can be observed that the designed fuzzy sliding mode controller can control the 6-DOF motion of AAR-2 quickly and precisely.

  11. 49 CFR 232.603 - Design, interoperability, and configuration management requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...: 1999; Revised 2002, 2007); (3) AAR S-4220, “ECP Cable-Based Brake DC Power Supply—Performance...; Revised: 2004); (7) AAR S-4260, “ECP Brake and Wire Distributed Power Interoperability Test Procedures...) Approval. A freight train or freight car equipped with an ECP brake system and equipment covered by the AAR...

  12. ADRA2A is involved in neuro-endocrine regulation of bone resorption.

    PubMed

    Mlakar, Vid; Jurkovic Mlakar, Simona; Zupan, Janja; Komadina, Radko; Prezelj, Janez; Marc, Janja

    2015-07-01

    Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through β2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of α2A-AR in bone. The aim of this study was to investigate the presence of α2A-AR and its involvement in neuro-endocrine signalling of bone remodelling in humans. Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to investigate α2A-AR receptor presence and localization in bone cells. Functionality of rs553668 and rs1800544 single nucleotide polymorphism SNPs located in α2A-AR gene was analysed by qPCR expression on bone samples and luciferase reporter assay in human osteosarcoma HOS cells. Using real-time PCR, genetic association study between rs553668 A>G and rs1800544 C>G SNPs and major bone markers was performed on 661 Slovenian patients with osteoporosis. α2A-AR is expressed in osteoblasts and lining cells but not in osteocytes. SNP rs553668 has a significant influence on α2A-AR mRNA level in human bone samples through the stability of mRNA. α2A-AR gene locus associates with important bone remodelling markers (BMD, CTX, Cathepsin K and pOC). The results of this study are providing comprehensive new evidence that α2A-AR is involved in neuro-endocrine signalling of bone turnover and development of osteoporosis. As shown by our results the neurological signalling is mediated through osteoblasts and result in bone resorption. Genetic study showed association of SNPs in α2A-AR gene locus with bone remodelling markers, identifying the individuals with higher risk of development of osteoporosis. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  13. ADRA2A is involved in neuro-endocrine regulation of bone resorption

    PubMed Central

    Mlakar, Vid; Jurkovic Mlakar, Simona; Zupan, Janja; Komadina, Radko; Prezelj, Janez; Marc, Janja

    2015-01-01

    Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through β2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of α2A-AR in bone. The aim of this study was to investigate the presence of α2A-AR and its involvement in neuro-endocrine signalling of bone remodelling in humans. Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to investigate α2A-AR receptor presence and localization in bone cells. Functionality of rs553668 and rs1800544 single nucleotide polymorphism SNPs located in α2A-AR gene was analysed by qPCR expression on bone samples and luciferase reporter assay in human osteosarcoma HOS cells. Using real-time PCR, genetic association study between rs553668 A>G and rs1800544 C>G SNPs and major bone markers was performed on 661 Slovenian patients with osteoporosis. α2A-AR is expressed in osteoblasts and lining cells but not in osteocytes. SNP rs553668 has a significant influence on α2A-AR mRNA level in human bone samples through the stability of mRNA. α2A-AR gene locus associates with important bone remodelling markers (BMD, CTX, Cathepsin K and pOC). The results of this study are providing comprehensive new evidence that α2A-AR is involved in neuro-endocrine signalling of bone turnover and development of osteoporosis. As shown by our results the neurological signalling is mediated through osteoblasts and result in bone resorption. Genetic study showed association of SNPs in α2A-AR gene locus with bone remodelling markers, identifying the individuals with higher risk of development of osteoporosis. PMID:25818344

  14. Forebrain pathway for auditory space processing in the barn owl.

    PubMed

    Cohen, Y E; Miller, G L; Knudsen, E I

    1998-02-01

    The forebrain plays an important role in many aspects of sound localization behavior. Yet, the forebrain pathway that processes auditory spatial information is not known for any species. Using standard anatomic labeling techniques, we used a "top-down" approach to trace the flow of auditory spatial information from an output area of the forebrain sound localization pathway (the auditory archistriatum, AAr), back through the forebrain, and into the auditory midbrain. Previous work has demonstrated that AAr units are specialized for auditory space processing. The results presented here show that the AAr receives afferent input from Field L both directly and indirectly via the caudolateral neostriatum. Afferent input to Field L originates mainly in the auditory thalamus, nucleus ovoidalis, which, in turn, receives input from the central nucleus of the inferior colliculus. In addition, we confirmed previously reported projections of the AAr to the basal ganglia, the external nucleus of the inferior colliculus (ICX), the deep layers of the optic tectum, and various brain stem nuclei. A series of inactivation experiments demonstrated that the sharp tuning of AAr sites for binaural spatial cues depends on Field L input but not on input from the auditory space map in the midbrain ICX: pharmacological inactivation of Field L eliminated completely auditory responses in the AAr, whereas bilateral ablation of the midbrain ICX had no appreciable effect on AAr responses. We conclude, therefore, that the forebrain sound localization pathway can process auditory spatial information independently of the midbrain localization pathway.

  15. Age estimation based on aspartic acid racemization in elastin from the yellow ligaments.

    PubMed

    Ritz-Timme, S; Laumeier, I; Collins, M

    2003-04-01

    The yellow ligaments of the spine are characterized by an exceptionally high content of elastin, a protein with a proved longevity in several human tissues. This unique biochemical composition suggested a suitability of yellow ligaments for age estimation based on aspartic acid racemization (AAR), which was tested by determination of AAR in total tissue specimens and in purified elastin from yellow ligaments of individuals of known age. AAR was found to increase with age in both sample sets. The purified elastin samples exhibited a much faster kinetics than the total tissue, with ca. 3.7-4.6-fold higher apparent rates. The relationship between AAR and age was much closer in the purified elastin samples ( r=0.96-0.99) and it can therefore be used as a basis for biochemical age estimation. The analysis of total tissue samples cannot be recommended since the AAR values can be strongly influenced even by slight, histologically non-detectable variations in the collagen content. Age estimation based on AAR in purified elastin from yellow ligaments may be a valuable additional tool in the identification of unidentified cadavers, especially in cases where other methods cannot be applied (e.g. no available teeth, body parts).

  16. Aminostratigraphy of Subsurface Units, Eastern Albemarle Sound and Northern Outer Banks, North Carolina

    NASA Astrophysics Data System (ADS)

    Wehmiller, J. F.; Thieler, E. R.; York, L. L.; Pellerito, V.

    2002-12-01

    The Quaternary geochronology of subsurface and emergent units on the US Atlantic Coastal Plain aids the understanding of the geologic framework that affects Holocene coastal processes. Amino acid racemization (AAR) and radiocarbon results for mollusk samples from a variety of sampling sites along the NC coastal plain contribute to this chronologic framework. Recent drilling on the northern Outer Banks has yielded AAR/14C results that are compared with existing data for samples from nearby inner shelf or beach sites, or from subsurface sampling in mainland Dare County (Riggs and others, 1992). AAR data serve to delineate stratigraphic units; suitably calibrated, AAR data can be used to estimate ages for units with no independent radiometric data. New AAR data from two holes, OBX-5 and OBX-8 (north and central portions of cross-section D-D' of Riggs et al., 1992), identify three pre-Holocene aminozones. The oldest one (OBX-5, 135' depth) corresponds to an early/middle Pleistocene aminozone (AZ-4) seen in other subsurface sections in the region (Riggs et al., 1992). Based on AAR, AZ-4 is approximately 2/3 the age of the James City Formation, a mapped early Pleistocene unit exposed in central NC. Two younger aminozones are seen in superposition in OBX-8, at 65' and 114'. These aminozones have D/L values that are slightly greater than those seen in AZ-2 and AZ-3, interpreted as late and late/middle Pleistocene (Riggs et al., 1992), respectively. Infinite or near-infinite 14C dates at depths between 65' and 104' in OBX-8 confirm the Pleistocene age assignment based on AAR. Radiocarbon and AAR constrain the boundary between the early Holocene and AZ-4 (early/middle Pleistocene) in OBX-5 to an interval between ca. 110' and 135' depth; intervening late Pleistocene strata may be present but are not identified based on chronologic data. Paired 14C/AAR analysis of reworked/transported beach or shelf shell in the region supports the relative ages seen in the OBX holes and

  17. Chapter K: Progress in the Evaluation of Alkali-Aggregate Reaction in Concrete Construction in the Pacific Northwest, United States and Canada

    USGS Publications Warehouse

    Shrimer, Fred H.

    2005-01-01

    The supply of aggregates suitable for use in construction and maintenance of infrastructure in western North America is a continuing concern to the engineering and resources-management community. Steady population growth throughout the region has fueled demand for high-quality aggregates, in the face of rapid depletion of existing aggregate resources and slow and difficult permitting of new sources of traditional aggregate types. In addition to these challenges, the requirement for aggregates to meet various engineering standards continues to increase. In addition to their physical-mechanical properties, other performance characteristics of construction aggregates specifically depend on their mineralogy and texture. These properties can result in deleterious chemical reactions when aggregate is used in concrete mixes. When this chemical reaction-termed 'alkali-aggregate reaction' (AAR)-occurs, it can pose a major problem for concrete structures, reducing their service life and requiring expensive repair or even replacement of the concrete. AAR is thus to be avoided in order to promote the longevity of concrete structures and to ensure that public moneys invested in infrastructure are well spent. Because the AAR phenomenon is directly related to the mineral composition, texture, and petrogenesis of the rock particles that make up aggregates, an understanding of the relation between the geology and the performance of aggregates in concrete is important. In the Pacific Northwest, some aggregates have a moderate to high AAR potential, but many others have no or only a low AAR potential. Overall, AAR is not as widespread or serious a problem in the Pacific Northwest as in other regions of North America. The identification of reactive aggregates in the Pacific Northwest and the accurate prediction of their behavior in concrete continue to present challenges for the assessment and management of geologic resources to the owners and operators of pits and quarries and to the

  18. Psychophysiological Assessment in Pilots Performing Challenging Simulated and Real Flight Maneuvers.

    PubMed

    Johannes, Bernd; Rothe, Stefanie; Gens, André; Westphal, Soeren; Birkenfeld, Katja; Mulder, Edwin; Rittweger, Jörn; Ledderhos, Carla

    2017-09-01

    The objective assessment of psychophysiological arousal during challenging flight maneuvers is of great interest to aerospace medicine, but remains a challenging task. In the study presented here, a vector-methodological approach was used which integrates different psychophysiological variables, yielding an integral arousal index called the Psychophysiological Arousal Value (PAV). The arousal levels of 15 male pilots were assessed during predetermined, well-defined flight maneuvers performed under simulated and real flight conditions. The physiological data, as expected, revealed inter- and intra-individual differences for the various measurement conditions. As indicated by the PAV, air-to-air refueling (AAR) turned out to be the most challenging task. In general, arousal levels were comparable between simulator and real flight conditions. However, a distinct difference was observed when the pilots were divided by instructors into two groups based on their proficiency in AAR with AWACS (AAR-Novices vs. AAR-Professionals). AAR-Novices had on average more than 2000 flight hours on other aircrafts. They showed higher arousal reactions to AAR in real flight (contact: PAV score 8.4 ± 0.37) than under simulator conditions (7.1 ± 0.30), whereas AAR-Professionals did not (8.5 ± 0.46 vs. 8.8 ± 0.80). The psychophysiological arousal value assessment was tested in field measurements, yielding quantifiable arousal differences between proficiency groups of pilots during simulated and real flight conditions. The method used in this study allows an evaluation of the psychophysiological cost during a certain flying performance and thus is possibly a valuable tool for objectively evaluating the actual skill status of pilots.Johannes B, Rothe S, Gens A, Westphal S, Birkenfeld K, Mulder E, Rittweger J, Ledderhos C. Psychophysiological assessment in pilots performing challenging simulated and real flight maneuvers. Aerosp Med Hum Perform. 2017; 88(9):834-840.

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

    Lopez-Buendia, A.M.; Climent, V.; Verdu, P.

    The reactivity of carbonate rock with the alkali content of cement, commonly called alkali-carbonate reaction (ACR), has been investigated. Alkali-silica reaction (ASR) can also contribute in the alkali-aggregate reaction (AAR) in carbonate rock, mainly due to micro- and crypto-crystalline quartz or clay content in carbonate aggregate. Both ACR and ASR can occur in the same system, as has been also evidenced on this paper. Carbonate aggregate samples were selected using lithological reactivity criteria, taking into account the presence of dedolomitization, partial dolomitization, micro- and crypto-crystalline quartz. Selected rocks include calcitic dolostone with chert (CDX), calcitic dolostone with dedolomitization (CDD), limestonemore » with chert (LX), marly calcitic dolostone with partial dolomitization (CD), high-porosity ferric dolostone with clays (FD). To evaluate the reactivity, aggregates were studied using expansion tests following RILEM AAR-2, AAR-5, a modification using LiOH AAR-5Li was also tested. A complementary study was done using petrographic monitoring with polarised light microscopy on aggregates immersed in NaOH and LiOH solutions after different ages. SEM-EDAX has been used to identify the presence of brucite as a product of dedolomitization. An ACR reaction showed shrinkage of the mortar bars in alkaline solutions explained by induced dedolomitization, while an ASR process typically displayed expansion. Neither shrinkage nor expansion was observed when mortar bars were immersed in solutions of lithium hydroxide. Carbonate aggregate classification with AAR pathology risk has been elaborated based on mechanical behaviours by expansion and shrinkage. It is proposed to be used as a petrographic method for AAR diagnosis to complement the RILEM AAR1 specifically for carbonate aggregate. Aggregate materials can be classified as I (non-reactive), II (potentially reactive), and III (probably reactive), considering induced dedolomitization ACR

  20. A feasibility study evaluating effectiveness of an intervention to implement brief tobacco cessation counseling in community chain pharmacies

    PubMed Central

    Patwardhan, Pallavi D.; Chewning, Betty A.

    2016-01-01

    Objective To test the feasibility of implementing ask-advise-refer (AAR) in representative community chain pharmacies serving low socioeconomic areas, and to assess the effectiveness of a multimodal intervention on short-term implementation of AAR. Design Randomized controlled trial Settings Sixteen community chain pharmacies in South-central Wisconsin Intervention A multimodal intervention including: 1) training to implement AAR, 2) workflow integration recommendations, 3) a cessation poster to create awareness, and 4) a support visit. Main outcome measures Number of patrons asked about their tobacco use, number of tobacco users advised to quit, number of quitline cards given, and number of tobacco users enrolled in the quitline. Results As hypothesized, the multimodal intervention significantly predicted the number of patrons asked (estimate=4.84, incidence rate ratios[IRR]=127.2; p<0.001) tobacco users advised (estimate=2.12, IRR=8.33; p<0.01), quitline cards distributed (estimate=1.04, IRR=2.82; p<0.05), and tobacco users enrolled in the quitline (estimate=2.31, IRR=10.13; p<0.001). Conclusion This trial demonstrates the feasibility of implementing AAR in routine community pharmacy practice. This trial also indicates the short-term effectiveness of the intervention in facilitating AAR, implementation in partnership with other public health services and systems. More research is needed to evaluate the generalizability, effectiveness and sustainability of AAR, including factors influencing adoption and the impact on cessation. PMID:22825231

  1. Methods for Kinetic and Thermodynamic Analysis of Aminoacyl-tRNA Synthetases

    PubMed Central

    Francklyn, Christopher S.; First, Eric A.; Perona, John J.; Hou, Ya-Ming

    2008-01-01

    The accuracy of protein synthesis relies on the ability of aminoacyl-tRNA synthetases (aaRSs) to discriminate among true and near cognate substrates. To date, analysis of aaRSs function, including identification of residues of aaRS participating in amino acid and tRNA discrimination, has largely relied on the steady state kinetic pyrophosphate exchange and aminoacylation assays. Pre-steady state kinetic studies investigating a more limited set of aaRS systems have also been undertaken to assess the energetic contributions of individual enzyme-substrate interactions, particularly in the adenylation half reaction. More recently, a renewed interest in the use of rapid kinetics approaches for aaRSs has led to their application to several new aaRS systems, resulting in the identification of mechanistic differences that distinguish the two structurally distinct aaRS classes. Here, we review the techniques for thermodynamic and kinetic analysis of aaRS function. Following a brief survey of methods for the preparation of materials and for steady state kinetic analysis, this review will describe pre-steady state kinetic methods employing rapid quench and stopped-flow fluorescence for analysis of the activation and aminoacyl transfer reactions. Application of these methods to any aaRS system allows the investigator to derive detailed kinetic mechanisms for the activation and aminoacyl transfer reactions, permitting issues of substrate specificity, stereochemical mechanism, and inhibitor interaction to be addressed in a rigorous and quantitative fashion. PMID:18241792

  2. Cluster in the Auroral Acceleration Region

    NASA Technical Reports Server (NTRS)

    Pickett, Jolene S.; Fazakerley, Andrew N.; Marklund, Gorun; Dandouras, Iannis; Christopher, Ivar W.; Kistler, Lynn; Lucek, Elizabeth; Masson, Arnaud; Taylor, Matthew G.; Mutel, Robert L.; hide

    2010-01-01

    Due to a fortuitous evolution of the Cluster orbit, the Cluster spacecraft penetrated for the first time in its mission the heart of Earth's auroral acceleration region (AAR) in December 2009 and January 2010. During this time a special AAR campaign was carried out by the various Cluster instrument teams with special support from ESA and NASA facilities. We present some of the first multi-spacecraft observations of the waves, particles and fields made during that campaign. The Cluster spacecraft configuration during these AAR passages was such that it allowed us to explore the differences in the signatures of waves, particles, and fields on the various spacecraft in ways not possible with single spacecraft. For example, one spacecraft was more poleward than the other three (C2), one was at higher altitude (C1), and one of them (0) followed another (C4) through the AAR on approximately the same track but delayed by three minutes. Their separations were generally on the order of a few thousand km or less and occasionally two of them were lying along the same magnetic field line. We will show some of the first analyses of the data obtained during the AAR campaign, where upward and downward current regions, and the waves specifically associated with those regions, as well as the auroral cavities, were observed similarly and differently on the various spacecraft, helping us to explore the spatial, as well as the temporal, aspects of processes occurring in the AAR.

  3. Structure-Activity Relationships of Truncated C2- or C8-Substituted Adenosine Derivatives as Dual Acting A2A and A3 Adenosine Receptor Ligands

    PubMed Central

    Hou, Xiyan; Majik, Mahesh S.; Kim, Kyunglim; Pyee, Yuna; Lee, Yoonji; Alexander, Varughese; Chung, Hwa-Jin; Lee, Hyuk Woo; Chandra, Girish; Lee, Jin Hee; Park, Seul-gi; Choi, Won Jun; Kim, Hea Ok; Phan, Khai; Gao, Zhan-Guo; Jacobson, Kenneth A.; Choi, Sun; Lee, Sang Kook; Jeong, Lak Shin

    2011-01-01

    Truncated N6-substituted-4′-oxo- and 4′-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A2A and A3 adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA2AAR, but hydrophobic C8 substitution abolished binding at the hA2AAR. However, most of synthesized compounds displayed medium to high binding affinity at the hA3AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA2AAR agonists. C2 substitution probed geometrically through hA2AAR-docking, was important for binding in order of hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually as hA2AAR agonist and hA3AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases. PMID:22142423

  4. Amino acid repeats avert mRNA folding through conservative substitutions and synonymous codons, regardless of codon bias.

    PubMed

    Barik, Sailen

    2017-12-01

    A significant number of proteins in all living species contains amino acid repeats (AARs) of various lengths and compositions, many of which play important roles in protein structure and function. Here, I have surveyed select homopolymeric single [(A)n] and double [(AB)n] AARs in the human proteome. A close examination of their codon pattern and analysis of RNA structure propensity led to the following set of empirical rules: (1) One class of amino acid repeats (Class I) uses a mixture of synonymous codons, some of which approximate the codon bias ratio in the overall human proteome; (2) The second class (Class II) disregards the codon bias ratio, and appears to have originated by simple repetition of the same codon (or just a few codons); and finally, (3) In all AARs (including Class I, Class II, and the in-betweens), the codons are chosen in a manner that precludes the formation of RNA secondary structure. It appears that the AAR genes have evolved by orchestrating a balance between codon usage and mRNA secondary structure. The insights gained here should provide a better understanding of AAR evolution and may assist in designing synthetic genes.

  5. Structure-activity relationships of truncated C2- or C8-substituted adenosine derivatives as dual acting A₂A and A₃ adenosine receptor ligands.

    PubMed

    Hou, Xiyan; Majik, Mahesh S; Kim, Kyunglim; Pyee, Yuna; Lee, Yoonji; Alexander, Varughese; Chung, Hwa-Jin; Lee, Hyuk Woo; Chandra, Girish; Lee, Jin Hee; Park, Seul-Gi; Choi, Won Jun; Kim, Hea Ok; Phan, Khai; Gao, Zhan-Guo; Jacobson, Kenneth A; Choi, Sun; Lee, Sang Kook; Jeong, Lak Shin

    2012-01-12

    Truncated N(6)-substituted-4'-oxo- and 4'-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A(2A) and A(3) adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross-coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA(2A)AR, but hydrophobic C8 substitution abolished binding at the hA(2A)AR. However, most of synthesized compounds displayed medium to high binding affinity at the hA(3)AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA(2A)AR agonists. C2 substitution probed geometrically through hA(2A)AR docking was important for binding in order of hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually as hA(2A)AR agonist and hA(3)AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases.

  6. 78 FR 75573 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-12

    ..., facsimile number (202) 646-3347, or email address [email protected] (HSEEP) After Action Report (AAR) Improvement Plan (IP). Type of Information Collection: Revision of a... Exercise and Evaluation Program (HSEEP) After Action Report (AAR) Improvement Plan (IP). Abstract: The...

  7. Automatic anatomy recognition in post-tonsillectomy MR images of obese children with OSAS

    NASA Astrophysics Data System (ADS)

    Tong, Yubing; Udupa, Jayaram K.; Odhner, Dewey; Sin, Sanghun; Arens, Raanan

    2015-03-01

    Automatic Anatomy Recognition (AAR) is a recently developed approach for the automatic whole body wide organ segmentation. We previously tested that methodology on image cases with some pathology where the organs were not distorted significantly. In this paper, we present an advancement of AAR to handle organs which may have been modified or resected by surgical intervention. We focus on MRI of the neck in pediatric Obstructive Sleep Apnea Syndrome (OSAS). The proposed method consists of an AAR step followed by support vector machine techniques to detect the presence/absence of organs. The AAR step employs a hierarchical organization of the organs for model building. For each organ, a fuzzy model over a population is built. The model of the body region is then described in terms of the fuzzy models and a host of other descriptors which include parent to offspring relationship estimated over the population. Organs are recognized following the organ hierarchy by using an optimal threshold based search. The SVM step subsequently checks for evidence of the presence of organs. Experimental results show that AAR techniques can be combined with machine learning strategies within the AAR recognition framework for good performance in recognizing missing organs, in our case missing tonsils in post-tonsillectomy images as well as in simulating tonsillectomy images. The previous recognition performance is maintained achieving an organ localization accuracy of within 1 voxel when the organ is actually not removed. To our knowledge, no methods have been reported to date for handling significantly deformed or missing organs, especially in neck MRI.

  8. Alpha-1A Adrenergic receptor activation increases inhibitory tone in CA1 hippocampus

    PubMed Central

    Hillman, Kristin L.; Lei, Saobo; Doze, Van A.

    2009-01-01

    The endogenous catecholamine norepinephrine (NE) exhibits anti-epileptic properties, however it is not well understood which adrenergic receptor (AR) mediates this effect. The aim of this study was to investigate α1-adrenergic receptor (AR) activation in region CA1 of the hippocampus, a subcortical structure often implicated in temporal lobe epilepsies. Using cell-attached and whole-cell recordings in rat hippocampal slices, we confirmed that selective α1-AR activation increases action potential firing in a subpopulation of CA1 interneurons. We found that this response is mediated via the α1A-AR subtype, initiated by sodium influx, and appears independent of second messenger signaling. In CA1 pyramidal cells, α1A-AR activation decreases activity due to increased pre-synaptic GABA and somatostatin release. Examination of post-synaptic receptor involvement revealed that while GABAA receptors mediate the majority of α1A-adrenergic effects on CA1 pyramidal cells, significant contributions are also made by GABAB and somatostatin receptors. Finally, to test whether α1A-AR activation could have potential therapeutic implications, we performed AR agonist challenges using two in vitro epileptiform models. When GABAA receptors were available, α1A-AR activation significantly decreased epileptiform bursting in CA1. Together, our findings directly link stimulation of the α1A-AR subtype to release of GABA and somatostatin at the single cell level and suggest that α1A-AR activation may represent one mechanism by which NE exerts anti-epileptic effects within the hippocampus. PMID:19201164

  9. Alkali-aggregate reactivity of typical siliceious glass and carbonate rocks in alkali-activated fly ash based geopolymers

    NASA Astrophysics Data System (ADS)

    Lu, Duyou; Liu, Yongdao; Zheng, Yanzeng; Xu, Zhongzi; Shen, Xiaodong

    2013-08-01

    For exploring the behaviour of alkali-aggregate reactivity (AAR) in alkali-activated geopolymeric materials and assessing the procedures for testing AAR in geopolymers, the expansion behaviour of fly ash based geopolymer mortars with pure silica glass and typical carbonate rocks were studied respectively by curing at various conditions, i.e. 23°C and 38°C with relative humidity over 95%, immersed in 1M NaOH solution at 80°C. Results show that, at various curing conditions, neither harmful ASR nor harmful ACR was observed in geopolymers with the criteria specified for OPC system. However, with the change of curing conditions, the geopolymer binder and reactive aggregates may experience different reaction processes leading to quite different dimensional changes, especially with additional alkalis and elevated temperatures. It suggests that high temperature with additional alkali for accelerating AAR in traditional OPC system may not appropriate for assessing the alkali-aggregate reactivity behaviour in geopolymers designed for normal conditions. On the other hand, it is hopeful to control the dimensional change of geopolymer mortar or concrete by selecting the type of aggregates and the appropriate curing conditions, thus changing the harmful AAR in OPC into beneficial AAR in geopolymers and other alkali-activated cementitious systems.

  10. 78 FR 48765 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-09

    ... safety appliance arrangements on modern railcar types not explicitly covered by 49 CFR Part 231. The Task... all car types, plus industry safety appliance standards for specific car types. These industry... arrangements for individual car types. AAR also included deviation tables that show where the AAR standard...

  11. 78 FR 10263 - Proposed Collection; Comment Request for Form 8082

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-13

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 8082, Notice of Inconsistent Treatment or Administrative Adjustment Request (AAR). DATES: Written... Inconsistent Treatment or Administrative Adjustment Request (AAR). OMB Number: 1545-0790. Form Number: 8082...

  12. 78 FR 60301 - Agency Information Collection Activities: Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... Evaluation Program (HSEEP) After Action Report (AAR) Improvement Plan (IP). DATES: Comments must be submitted...) Improvement Plan (IP) provides a standardized method for reporting the results of preparedness exercises and identifying, correcting and sharing as appropriate strengths and areas for improvement. Thus, the HSEEP AAR/IP...

  13. Using Rapid Improvement Events for Disaster After-Action Reviews: Experience in a Hospital Information Technology Outage and Response.

    PubMed

    Little, Charles M; McStay, Christopher; Oeth, Justin; Koehler, April; Bookman, Kelly

    2018-02-01

    The use of after-action reviews (AARs) following major emergency events, such as a disaster, is common and mandated for hospitals and similar organizations. There is a recurrent challenge of identified problems not being resolved and repeated in subsequent events. A process improvement technique called a rapid improvement event (RIE) was used to conduct an AAR following a complete information technology (IT) outage at a large urban hospital. Using RIE methodology to conduct the AAR allowed for the rapid development and implementation of major process improvements to prepare for future IT downtime events. Thus, process improvement methodology, particularly the RIE, is suited for conducting AARs following disasters and holds promise for improving outcomes in emergency management. Little CM , McStay C , Oeth J , Koehler A , Bookman K . Using rapid improvement events for disaster after-action reviews: experience in a hospital information technology outage and response. Prehosp Disaster Med. 2018;33(1):98-100.

  14. Selective regulation of nuclear orphan receptors 4A by adenosine receptor subtypes in human mast cells

    PubMed Central

    Zhang, Li; Paine, Catherine

    2010-01-01

    Nuclear orphan receptors 4A (NR4A) are early responsive genes that belong to the superfamily of hormone receptors and comprise NR4A1, NR4A2 and NR4A3. They have been associated to transcriptional activation of multiple genes involved in inflammation, apoptosis and cell cycle control. Here, we establish a link between NR4As and adenosine, a paradoxical inflammatory molecule that can contribute to persistence of inflammation or mediate inflammatory shutdown. Transcriptomics screening of the human mast cell-line HMC-1 revealed a sharp induction of transcriptionally active NR4A2 and NR4A3 by the adenosine analogue NECA. The concomitant treatment of NECA and the adenosine receptor A2A (A2AAR) selective antagonist SCH-58261 exaggerated this effect, suggesting that upregulation of these factors in mast cells is mediated by other AR subtypes (A2B and A3) and that A2AAR activation counteracts NR4A2 and NR4A3 induction. In agreement with this, A2AAR-silencing amplified NR4A induction by NECA. Interestingly, a similar A2AAR modulatory effect was observed on ERK1/2 phosphorylation because A2AAR blockage exacerbated NECA-mediated phosphorylation of ERK1/2. In addition, PKC or MEK1/2 inhibition prevented ERK1/2 phosphorylation and antagonized AR-mediated induction of NR4A2 and NR4A3, suggesting the involvement of these kinases in AR to NR4A signaling. Finally, we observed that selective A2AAR activation with CGS-21680 blocked PMA-induced ERK1/2 phosphorylation and modulated the overexpression of functional nuclear orphan receptors 4A. Taken together, these results establish a novel PKC/ERK/nuclear orphan receptors 4A axis for adenosinergic signaling in mast cells, which can be modulated by A2AAR activation, not only in the context of adenosine but of other mast cell activating stimuli as well. PMID:21234122

  15. Multi-Inhibitory Effects of A2A Adenosine Receptor Signaling on Neutrophil Adhesion Under Flow.

    PubMed

    Yago, Tadayuki; Tsukamoto, Hiroki; Liu, Zhenghui; Wang, Ying; Thompson, Linda F; McEver, Rodger P

    2015-10-15

    A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, β2 integrin-dependent slow rolling and chemokine-induced, β2 integrin-dependent arrest on ICAM-1. ATL313 inhibited selectin-induced β2 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain "swing-out," which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti-β2 integrin Ab. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1, and β2 integrin-triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A and its substrate C-terminal Src kinase, an inhibitor of SFKs. Treating neutrophils with a protein kinase A inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-α challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases. Copyright © 2015 by The American Association of Immunologists, Inc.

  16. Multi-inhibitory effects of A2A adenosine receptor signaling on neutrophil adhesion under flow**

    PubMed Central

    Yago, Tadayuki; Tsukamoto, Hiroki; Liu, Zhenghui; Wang, Ying; Thompson, Linda F.; McEver, Rodger P.

    2015-01-01

    A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, β2 integrin-dependent slow rolling and chemokine-induced, β2 integrin-dependent arrest on ICAM-1. ATL313 inhibited selectin-induced β2 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain “swing-out”, which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti-β2 integrin antibody. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1 (Rap1), and β2 integrin-triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A (PKA) and its substrate C-terminal Src kinase (Csk), an inhibitor of SFKs. Treating neutrophils with a PKA inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-α challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases. PMID:26355151

  17. Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group

    PubMed Central

    Pleyer, Lisa; Döhner, Hartmut; Dombret, Hervé; Seymour, John F.; Schuh, Andre C.; Beach, CL; Swern, Arlene S.; Burgstaller, Sonja; Stauder, Reinhard; Girschikofsky, Michael; Sill, Heinz; Schlick, Konstantin; Thaler, Josef; Halter, Britta; Machherndl Spandl, Sigrid; Zebisch, Armin; Pichler, Angelika; Pfeilstöcker, Michael; Autzinger, Eva M.; Lang, Alois; Geissler, Klaus; Voskova, Daniela; Sperr, Wolfgang R.; Hojas, Sabine; Rogulj, Inga M.; Andel, Johannes; Greil, Richard

    2017-01-01

    We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort; n = 214) with AAR patients meeting the same inclusion criteria (“AAR (001-like)” cohort; n = 95). The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (p = 0.616) for “AML-001” versus “AAR (001-like)” cohorts, respectively. Secondly, we pooled data from both cohorts (n = 309) and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6) months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (n = 95) versus all AAR patients with World Health Organization (WHO)-defined AML (“AAR (WHO

  18. Defining Educational Research: A Perspective of/on Presidential Addresses and the Australian Association for Research in Education

    ERIC Educational Resources Information Center

    Lingard, Bob; Gale, Trevor

    2010-01-01

    This paper is concerned with the definition of the field of educational research and the changing and developing role of the Australian Association for Research in Education (AARE) in representing and constituting this field. The evidence for the argument is derived from AARE Presidential Addresses across its 40-year history. The paper documents…

  19. 76 FR 55819 - Track Safety Standards; Concrete Crossties

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... geometry car that had operated over BNSF's Seadrift subdivision on December 14, 2010. According to AAR... is surprised that AAR asserts at this stage in the rulemaking process that the technology to perform... accuracy specified by Sec. 213.234, or \\1/8\\ of an inch, without mandating which technology should be used...

  20. Excellent amino acid racemization results from Holocene sand dollars

    NASA Astrophysics Data System (ADS)

    Kosnik, M.; Kaufman, D. S.; Kowalewski, M.; Whitacre, K.

    2015-12-01

    Amino acid racemization (AAR) is widely used as a cost-effective method to date molluscs in time-averaging and taphonomic studies, but it has not been attempted for echinoderms despite their paleobiological importance. Here we demonstrate the feasibility of AAR geochronology in Holocene aged Peronella peronii (Echinodermata: Echinoidea) collected from Sydney Harbour (Australia). Using standard HPLC methods we determined the extent of AAR in 74 Peronella tests and performed replicate analyses on 18 tests. We sampled multiple areas of two individuals and identified the outer edge as a good sampling location. Multiple replicate analyses from the outer edge of 18 tests spanning the observed range of D/Ls yielded median coefficients of variation < 4% for Asp, Phe, Ala, and Glu D/L values, which overlaps with the analytical precision. Correlations between D/L values across 155 HPLC injections sampled from 74 individuals are also very high (pearson r2 > 0.95) for these four amino acids. The ages of 11 individuals spanning the observed range of D/L values were determined using 14C analyses, and Bayesian model averaging was used to determine the best AAR age model. The averaged age model was mainly composed of time-dependent reaction kinetics models (TDK, 71%) based on phenylalanine (Phe, 94%). Modelled ages ranged from 14 to 5539 yrs, and the median 95% confidence interval for the 74 analysed individuals is ±28% of the modelled age. In comparison, the median 95% confidence interval for the 11 calibrated 14C ages was ±9% of the median age estimate. Overall Peronella yields exceptionally high-quality AAR D/L values and appears to be an excellent substrate for AAR geochronology. This work opens the way for time-averaging and taphonomic studies of echinoderms similar to those in molluscs.

  1. Smoking cessation treatment practices: recommendations for improved adoption on cardiology wards.

    PubMed

    Berndt, Nadine C; Bolman, Catherine; de Vries, Hein; Segaar, Dewi; van Boven, Irene; Lechner, Lilian

    2013-01-01

    Smoking cessation treatment practices described by the 5 A's (ask, advise, assess, assist, arrange) are not well applied at cardiology wards because of various reasons, such as a lack of time and appropriate skills of the nursing staff. Therefore, a simplified guideline proposing an ask-advise-refer (AAR) strategy was introduced in Dutch cardiac wards. This study aimed to identify factors that determine the intentions of cardiac ward heads in adopting the simplified AAR guideline, as ward heads are key decision makers in the adoption of new guidelines. Ward heads' perceptions of current smoking cessation practices at the cardiac ward were also investigated. A cross-sectional survey with written questionnaires was conducted among heads of cardiology wards throughout the Netherlands, of whom 117 (64%) responded. According to the heads of cardiac wards, smoking cessation practices by cardiologists and nurses were mostly limited to brief practices that are easy to conduct. Only a minority offered intensive counseling or arranged follow-up contact. Heads with strong intentions of adopting the AAR guideline differed significantly on motivational and organizational attributes and perceived more smoking cessation assistance by other health professionals than did heads with weak intentions of adopting. Positive attitudes, social support toward adoption, and perception of much assistance at the ward were significantly associated with increased intentions to adopt the AAR guideline. Brief smoking cessation practices are adequately performed at cardiac wards, but the most effective practices, offering assistance and arranging for follow-up, are less than optimal. The AAR guideline offers a more feasible approach for busy cardiology wards. To ensure successful adoption of this guideline, the heads of cardiac wards should be convinced of its advantages and be encouraged by a supportive work environment. Policies may also facilitate the adoption of the AAR guideline.

  2. An analysis of root cause identification and continuous quality improvement in public health H1N1 after-action reports.

    PubMed

    Singleton, Christa-Marie; Debastiani, Summer; Rose, Dale; Kahn, Emily B

    2014-01-01

    To identify the extent to which the Homeland Security Exercise and Evaluation Program's (HSEEP) After Action Report/Improvement Plan (AAR/IP) template was followed by public health entities and facilitated the identification of detailed corrective actions and continuous improvement. Data were drawn from the US H1N1 Public Health Emergency Response (PHER) federal grant awardees (n = 62). After action report/improvement plan text was examined to identify the presence of AAR/IP HSEEP elements and characterized as "minimally complete," "partially complete," or "complete." Corrective actions (CA) and recommendations within the IP focusing on performance deficits were coded as specific, measurable, and time-bound, and whether they were associated with a problem that met root cause criteria and whether the CA/recommendation was intended to address or fix the root cause. A total of 2619 CA/recommendations were identified. More than half (n = 1480, 57%) addressed root causes. Corrective actions/recommendations associated with complete AARs more frequently addressed root cause (58% vs 51%, χ = 9.1, P < 0.003) and were more specific (34% vs 23%, χ = 32.3, P < 0.0001), measurable (30% vs 18%, χ = 37.9, P < 0.0001), and time-bound (38% vs 15%, χ = 115.5, P < 0.0001) than partially complete AARs. The same pattern was not observed with completeness of IPs. Corrective actions and recommendations were similarly specific and measurable. Recommendations significantly addressed root cause more than CAs. Our analysis indicates a possible lack of awardee distinction between CA and recommendations in AARs. As HSEEP adapts to align with the 2011 National Preparedness Goal and National Preparedness System, future HSEEP documents should emphasize the importance of root cause analysis as a required element within AAR documents and templates in the exercise and real incident environment, as well as the need for specific and measurable CAs.

  3. Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification

    PubMed Central

    Fang, Pengfei; Guo, Min

    2015-01-01

    Aminoacyl-tRNA synthetases (aaRSs) are enzymes that catalyze the transfer of amino acids to their cognate tRNAs as building blocks for translation. Each of the aaRS families plays a pivotal role in protein biosynthesis and is indispensable for cell growth and survival. In addition, aaRSs in higher species have evolved important non-translational functions. These translational and non-translational functions of aaRS are attractive for developing antibacterial, antifungal, and antiparasitic agents and for treating other human diseases. The interplay between amino acids, tRNA, ATP, EF-Tu and non-canonical binding partners, had shaped each family with distinct pattern of key sites for regulation, with characters varying among species across the path of evolution. These sporadic variations in the aaRSs offer great opportunity to target these essential enzymes for therapy. Up to this day, growing numbers of aaRS inhibitors have been discovered and developed. Here, we summarize the latest developments and structural studies of aaRS inhibitors, and classify them with distinct binding modes into five categories. PMID:26670257

  4. Aminoacyl-tRNA synthetases database Y2K

    PubMed Central

    Szymanski, Maciej; Barciszewski, Jan

    2000-01-01

    The aminoacyl-tRNA synthetases (AARS) are a diverse group of enzymes that ensure the fidelity of transfer of genetic information from DNA into protein. They catalyse the attachment of amino acids to transfer RNAs and thereby establish the rules of the genetic code by virtue of matching the nucleotide triplet of the anticodon with its cognate amino acid. Currently, 818 AARS primary structures have been reported from archaebacteria, eubacteria, mitochondria, chloroplasts and eukaryotic cells. The database is a compilation of the amino acid sequences of all AARSs, known to date, which are available as separate entries or alignments of related proteins via the WWW at http://rose.man.poznan.pl/aars/index.html PMID:10592262

  5. Aminoacyl-tRNA synthetases database Y2K.

    PubMed

    Szymanski, M; Barciszewski, J

    2000-01-01

    The aminoacyl-tRNA synthetases (AARS) are a diverse group of enzymes that ensure the fidelity of transfer of genetic information from DNA into protein. They catalyse the attachment of amino acids to transfer RNAs and thereby establish the rules of the genetic code by virtue of matching the nucleotide triplet of the anticodon with its cognate amino acid. Currently, 818 AARS primary structures have been reported from archaebacteria, eubacteria, mitochondria, chloro-plasts and eukaryotic cells. The database is a compilation of the amino acid sequences of all AARSs, known to date, which are available as separate entries or alignments of related proteins via the WWW at http://rose.man.poznan.pl/aars/index.html

  6. 2014 Australian Association for Research in Education Presidential Address: Educational Research and the Tree of Knowledge in a Post Human Digital Age

    ERIC Educational Resources Information Center

    Moss, Julianne

    2016-01-01

    The 2014, 41st Australian Association for Research in Education (AARE) presidential address is both inspired and guided by the discursive genres of presidential addresses and the role of the president in a member association such as AARE. In the address, typically the president speaks to the members on an issue or issues that are to shape or…

  7. After-Action Reviews - who conducts them?

    Treesearch

    Anne E. Black; Kathleen Sutcliffe; Michelle Barton

    2009-01-01

    Reflecting on the links between intentions and outcomes is a key practice of a learning organization (Garvin 2000). The After-Action Review (AAR) is a formal reflection process intended to assist groups in capturing lessons learned from a task. AARs typically ask four questions regarding fire-response operations: (1) what did we set out to do, (2) what actually...

  8. Bifunctional staining for ex vivo determination of area at risk in rabbits with reperfused myocardial infarction

    PubMed Central

    Feng, Yuanbo; Ma, Zhan-Long; Chen, Feng; Yu, Jie; Cona, Marlein Miranda; Xie, Yi; Li, Yue; Ni, Yicheng

    2013-01-01

    AIM: To develop a method for studying myocardial area at risk (AAR) in ischemic heart disease in correlation with cardiac magnetic resonance imaging (cMRI). METHODS: Nine rabbits were anesthetized, intubated and subjected to occlusion and reperfusion of the left circumflex coronary artery (LCx) to induce myocardial infarction (MI). ECG-triggered cMRI with delayed enhancement was performed at 3.0 T. After euthanasia, the heart was excised with the LCx re-ligated. Bifunctional staining was performed by perfusing the aorta with a homemade red-iodized-oil (RIO) dye. The heart was then agar-embedded for ex vivo magnetic resonance imaging and sliced into 3 mm-sections. The AAR was defined by RIO-staining and digital radiography (DR). The perfusion density rate (PDR) was derived from DR for the AAR and normal myocardium. The MI was measured by in vivo delayed enhancement (iDE) and ex vivo delayed enhancement (eDE) cMRI. The AAR and MI were compared to validate the bifunctional straining for cardiac imaging research. Linear regression with Bland-Altman agreement, one way-ANOVA with Bonferroni’s multiple comparison, and paired t tests were applied for statistics. RESULTS: All rabbits tolerated well the surgical procedure and subsequent cMRI sessions. The open-chest occlusion and close-chest reperfusion of the LCx, double suture method and bifunctional staining were successfully applied in all animals. The percentage MI volumes globally (n = 6) and by slice (n = 25) were 36.59% ± 13.68% and 32.88% ± 12.38% on iDE, and 35.41% ± 12.25% and 32.40% ± 12.34% on eDE. There were no significant differences for MI determination with excellent linear regression correspondence (rglobal = 0.89; rslice = 0.9) between iDE and eDE. The percentage AAR volumes globally (n = 6) and by slice (n = 25) were 44.82% ± 15.18% and 40.04% ± 13.64% with RIO-staining, and 44.74% ± 15.98% and 40.48% ± 13.26% by DR showing high correlation in linear regression analysis (rglobal = 0.99; rslice

  9. Current Practice and Theoretical Foundations of the After Action Review

    DTIC Science & Technology

    2011-06-01

    Stephen L. Goldberg , Chief U.S. Army Research Institute for the Behavioral and Social Sciences 2511 Jefferson Davis Highway, Arlington, Virginia...were many occasions where 37 the facilitators’ knowledge of the battle tempo , dynamics, and resources added to the SA of team members. Such...attending AARs. There appear to be frequent variations in organizational status among participants in traditional industry AARs. In military

  10. The growing pipeline of natural aminoacyl-tRNA synthetase inhibitors for malaria treatment.

    PubMed

    Saint-Léger, Adélaïde; Sinadinos, Christopher; Ribas de Pouplana, Lluís

    2016-04-02

    Malaria remains a major global health problem. Parasite resistance to existing drugs makes development of new antimalarials an urgency. The protein synthesis machinery is an excellent target for the development of new anti-infectives, and aminoacyl-tRNA synthetases (aaRS) have been validated as antimalarial drug targets. However, avoiding the emergence of drug resistance and improving selectivity to target aaRS in apicomplexan parasites, such as Plasmodium falciparum, remain crucial challenges. Here we discuss such issues using examples of known inhibitors of P. falciparum aaRS, namely halofuginone, cladosporin and borrelidin (inhibitors of ProRS, LysRS and ThrRS, respectively). Encouraging recent results provide useful guidelines to facilitate the development of novel drug candidates which are more potent and selective against these essential enzymes.

  11. New Surgical Drapes for Observation of the Lower Extremities during Abdominal Aortic Repair.

    PubMed

    Obitsu, Yukio; Shigematsu, Hiroshi; Satou, Kazuhiro; Watanabe, Yoshiko; Saiki, Naozumi; Koizumii, Nobusato

    2010-01-01

    For the early diagnosis and therapy of peripheral thromboembolism (TE) as a complication of abdominal aortic repair (AAR), we developed and evaluated the usefulness of surgical drapes that permit observation of the lower extremities during AAR. Between January 2007 and June 2009, the handling, durability, and usefulness of new surgical drapes were evaluated during AAR in 157 patients with abdominal aortic aneurysms and 9 patients with peripheral arterial disease. The drapes are manufactured by Hogy Medical Co. Ltd. and made of a water-repellent, spun lace, non-woven fabric, including a transparent polyethylene film that covers the patients' legs. This transparent film enables inspection and palpation of the lower extremities during surgery for early diagnosis and therapy of peripheral TE. As a peripheral complication, 1 patient had right lower extremity TE. This was diagnosed immediately after anastomosis, thrombectomy was performed, and the remaining clinical course was uneventful. In all patients, the drapes permitted observation of the lower extremities , and the dorsal arteries were palpable. There were no problems with durability. New surgical drapes permit observation of the lower extremities during AAR for early diagnosis and treatment of peripheral TE.

  12. The alpha(2a)-adrenergic receptor plays a protective role in mouse behavioral models of depression and anxiety.

    PubMed

    Schramm, N L; McDonald, M P; Limbird, L E

    2001-07-01

    The noradrenergic system is involved in the regulation of many physiological and psychological processes, including the modulation of mood. The alpha(2)-adrenergic receptors (alpha(2)-ARs) modulate norepinephrine release, as well as the release of serotonin and other neurotransmitters, and are therefore potential targets for antidepressant and anxiolytic drug development. The current studies were undertaken to examine the role of the alpha(2A) subtype of alpha(2)-AR in mouse behavioral models of depression and anxiety. We have observed that the genetic knock-out of the alpha(2A)-AR makes mice less active in a modified version of Porsolt's forced swim test and insensitive to the antidepressant effects of the tricyclic drug imipramine in this paradigm. Furthermore, alpha(2A)-AR knock-out mice appear more anxious than wild-type C57 Bl/6 mice in the rearing and light-dark models of anxiety after injection stress. These findings suggest that the alpha(2A)-AR may play a protective role in some forms of depression and anxiety and that the antidepressant effects of imipramine may be mediated by the alpha(2A)-AR.

  13. Rocket-Based Combined Cycle Engine Concept Development

    NASA Technical Reports Server (NTRS)

    Ratekin, G.; Goldman, Allen; Ortwerth, P.; Weisberg, S.; McArthur, J. Craig (Technical Monitor)

    2001-01-01

    The development of rocket-based combined cycle (RBCC) propulsion systems is part of a 12 year effort under both company funding and contract work. The concept is a fixed geometry integrated rocket, ramjet, scramjet, which is hydrogen fueled and uses hydrogen regenerative cooling. The baseline engine structural configuration uses an integral structure that eliminates panel seals, seal purge gas, and closeout side attachments. Engine A5 is the current configuration for NASA Marshall Space Flight Center (MSFC) for the ART program. Engine A5 models the complete flight engine flowpath of inlet, isolator, airbreathing combustor, and nozzle. High-performance rocket thrusters are integrated into the engine enabling both low speed air-augmented rocket (AAR) and high speed pure rocket operation. Engine A5 was tested in GASL's new Flight Acceleration Simulation Test (FAST) facility in all four operating modes, AAR, RAM, SCRAM, and Rocket. Additionally, transition from AAR to RAM and RAM to SCRAM was also demonstrated. Measured performance demonstrated vision vehicle performance levels for Mach 3 AAR operation and ramjet operation from Mach 3 to 4. SCRAM and rocket mode performance was above predictions. For the first time, testing also demonstrated transition between operating modes.

  14. Tricyclic antidepressants exhibit variable pharmacological profiles at the α2A adrenergic receptor

    PubMed Central

    Cottingham, Christopher; Percival, Stefanie; Birky, Tana; Wang, Qin

    2014-01-01

    Antidepressant mechanisms of action remain shrouded in mystery, greatly hindering our ability to develop therapeutics which can fully treat patients suffering from depressive disorders. In an attempt to shed new light on this topic, we have undertaken a series of studies investigating actions of tricyclic antidepressant drugs (TCAs) at the α2A adrenergic receptor (AR), a centrally important receptor, dysregulation of which has been linked to depression. Our previous work established a particular TCA, desipramine, as an arrestin-biased α2AAR ligand driving receptor endocytosis and downregulation but not canonical heterotrimeric G protein-mediated signaling. The present work is aimed at broadening our understanding of how members of the TCA drug class act at the α2AAR, as we have selected the closely related but subtly different TCAs imipramine and amitriptyline for evaluation. Our data demonstrate that these drugs do also function as direct arrestin-biased α2AAR ligands. However, these data reveal differences in receptor affinity and in the extent/nature of arrestin recruitment to and endocytosis of α2AARs. Specifically, amitriptyline exhibits an approximately 14-fold stronger interaction with the receptor, is a weaker driver of arrestin recruitment, and preferentially recruits a different arrestin subtype. Extent of endocytosis is similar for all TCAs studied so far, and occurs in an arrestin-dependent manner, although imipramine uniquely retains a slight ability to drive α2AAR endocytosis in arrestin-null cells. These findings signify an important expansion of our mechanistic understanding of antidepressant pharmacology, and provide useful insights for future medicinal chemistry efforts. PMID:25128275

  15. Area at risk can be assessed by iodine-123-meta-iodobenzylguanidine single-photon emission computed tomography after myocardial infarction: a prospective study.

    PubMed

    Hedon, Christophe; Huet, Fabien; Ben Bouallegue, Fayçal; Vernhet, Hélène; Macia, Jean-Christophe; Cung, Thien-Tri; Leclercq, Florence; Cade, Stéphane; Cransac, Frédéric; Lattuca, Benoit; Vandenberghe, D'Arcy; Bourdon, Aurélie; Benkiran, Meriem; Vauchot, Fabien; Gervasoni, Richard; D'estanque, Emmanuel; Mariano-Goulart, Denis; Roubille, François

    2018-02-01

    Myocardial salvage is an important surrogate endpoint to estimate the impact of treatments in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to evaluate the correlation between cardiac sympathetic denervation area assessed by single-photon emission computed tomography (SPECT) using iodine-123-meta-iodobenzylguanidine (I-MIBG) and myocardial area at risk (AAR) assessed by cardiac magnetic resonance (CMR) (gold standard). A total of 35 postprimary reperfusion STEMI patients were enrolled prospectively to undergo SPECT using I-MIBG (evaluates cardiac sympathetic denervation) and thallium-201 (evaluates myocardial necrosis), and to undergo CMR imaging using T2-weighted spin-echo turbo inversion recovery for AAR and postgadolinium T1-weighted phase sensitive inversion recovery for scar assessment. I-MIBG imaging showed a wider denervated area (51.1±16.0% of left ventricular area) in comparison with the necrosis area on thallium-201 imaging (16.1±14.4% of left ventricular area, P<0.0001). CMR and SPECT provided similar evaluation of the transmural necrosis (P=0.10) with a good correlation (R=0.86, P<0.0001). AAR on CMR was not different compared with the denervated area (P=0.23) and was adequately correlated (R=0.56, P=0.0002). Myocardial salvage evaluated by SPECT imaging (mismatch denervated but viable myocardium) was significantly higher than by CMR (P=0.02). In patients with STEMI, I-MIBG SPECT, assessing cardiac sympathetic denervation may precisely evaluate the AAR, providing an alternative to CMR for AAR assessment.

  16. Analysis of Feedback in after Action Reviews

    DTIC Science & Technology

    1987-06-01

    CONNTSM Page INTRODUCTIUN . . . . . . . . . . . . . . . . . . . A Perspective on Feedback. . ....... • • ..... • 1 Overviev of %,•urrent Research...part of their training program . The AAR is in marked contrast to the critique method of feedback which is often used in military training. The AAR...feedback is task-inherent feedback. Task-inherent feedback refers to human-machine interacting systems, e.g., computers , where in a visual tracking task

  17. Learning in the thick of it.

    PubMed

    Darling, Marilyn; Parry, Charles; Moore, Joseph

    2005-01-01

    The U.S. Army's Opposing Force (OPFOR) is a 2,500-member brigade whose job is to help prepare soldiers for combat. Created to be the meanest, toughest foe that soldiers will ever face, OPFOR engages units-in-training in a variety of mock campaigns under a wide range of conditions. Every month, a fresh brigade of more than 4,000 soldiers takes on this standing enemy. OPFOR, which is stationed in the California desert, always has the home-court advantage. But the force being trained--called BLU FOR--is numerically and technologically superior. It possesses more resources and better, more available data. It is made up of experienced soldiers. And it knows just what to expect, because OPFOR shares its methods from previous campaigns with BLUFOR's commanders. In short, each BLUFOR brigade is given practically every edge. Yet OPFOR almost always wins. Underlying OPFOR's consistent success is the way it uses the after-action review (AAR), a method for extracting lessons from one event or project and applying them to others. AAR meetings became a popular business tool after Shell Oil began experimenting with them in 1998. Most corporate AARs, however, are faint echoes of the rigorous reviews performed by OPFOR. Companies tend to treat the process as a pro-forma wrap-up, drawing lessons from an action but rarely learning them. OPFOR's AARs, by contrast, generate raw material that is fed back into the execution cycle. And while OPFOR's reviews extract numerous lessons, the brigade does not consider a lesson to be learned until it is successfully applied and validated. It might not make sense for companies to adopt OPFOR's AAR processes in their entirety, but four fundamentals are mandatory: Lessons must benefit the team that extracts them. The AAR process must start atthe beginning of the activity. Lessons must link explicitly to future actions. And leaders must hold everyone, especially themselves, accountable for learning.

  18. Effects of cyclooxygenase inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia

    PubMed Central

    Chu, Louis M.; Robich, Michael P.; Bianchi, Cesario; Feng, Jun; Liu, Yuhong; Xu, Shu-Hua; Burgess, Thomas

    2012-01-01

    The cardiovascular effects of cyclooxygenase (COX) inhibition remain controversial, especially in the setting of cardiovascular comorbidities. We examined the effects of nonselective and selective COX inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia. Twenty-four intact male Yorkshire swine underwent left circumflex ameroid constrictor placement and were subsequently given either no drug (HCC; n = 8), a nonselective COX inhibitor (440 mg/day naproxen; HCNS; n = 8), or a selective COX-2 inhibitor (200 mg/day celecoxib; HCCX; n = 8). After 7 wk, myocardial functional was measured and myocardium from the nonischemic ventricle and ischemic area-at-risk (AAR) were analyzed. Regional function as measured by segmental shortening was improved in the AAR of HCCX compared with HCC. There was no significant difference in perfusion to the nonischemic ventricle between groups, but myocardial perfusion in the AAR was significantly improved in the HCCX group compared with controls at rest and during pacing. Endothelium-dependent microvessel relaxation was diminished by ischemia in HCC animals, but both naproxen and celecoxib improved vessel relaxation in the AAR compared with controls, and also decreased the vasoconstrictive response to serotonin. Thromboxane levels in the AAR were decreased in both HCNS and HCCX compared with HCC, whereas prostacyclin levels were decreased only in HCNS, corresponding to a decrease in prostacyclin synthase expression. Chronic ischemia increased apoptosis in Troponin T negative cells and intramyocardial fibrosis, both of which were reduced by celecoxib administration in the AAR. Capillary density was decreased in both the HCNS and HCCX groups. Protein oxidative stress was decreased in both HCNS and HCCX, whereas lipid oxidative stress was decreased only in the HCCX group. Thus nonselective and especially selective COX inhibition may have beneficial myocardial effects in the setting of

  19. Effects of cyclooxygenase inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia.

    PubMed

    Chu, Louis M; Robich, Michael P; Bianchi, Cesario; Feng, Jun; Liu, Yuhong; Xu, Shu-Hua; Burgess, Thomas; Sellke, Frank W

    2012-01-01

    The cardiovascular effects of cyclooxygenase (COX) inhibition remain controversial, especially in the setting of cardiovascular comorbidities. We examined the effects of nonselective and selective COX inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia. Twenty-four intact male Yorkshire swine underwent left circumflex ameroid constrictor placement and were subsequently given either no drug (HCC; n = 8), a nonselective COX inhibitor (440 mg/day naproxen; HCNS; n = 8), or a selective COX-2 inhibitor (200 mg/day celecoxib; HCCX; n = 8). After 7 wk, myocardial functional was measured and myocardium from the nonischemic ventricle and ischemic area-at-risk (AAR) were analyzed. Regional function as measured by segmental shortening was improved in the AAR of HCCX compared with HCC. There was no significant difference in perfusion to the nonischemic ventricle between groups, but myocardial perfusion in the AAR was significantly improved in the HCCX group compared with controls at rest and during pacing. Endothelium-dependent microvessel relaxation was diminished by ischemia in HCC animals, but both naproxen and celecoxib improved vessel relaxation in the AAR compared with controls, and also decreased the vasoconstrictive response to serotonin. Thromboxane levels in the AAR were decreased in both HCNS and HCCX compared with HCC, whereas prostacyclin levels were decreased only in HCNS, corresponding to a decrease in prostacyclin synthase expression. Chronic ischemia increased apoptosis in Troponin T negative cells and intramyocardial fibrosis, both of which were reduced by celecoxib administration in the AAR. Capillary density was decreased in both the HCNS and HCCX groups. Protein oxidative stress was decreased in both HCNS and HCCX, whereas lipid oxidative stress was decreased only in the HCCX group. Thus nonselective and especially selective COX inhibition may have beneficial myocardial effects in the setting of

  20. Electric potential structures of auroral acceleration region border from multi-spacecraft Cluster data

    NASA Astrophysics Data System (ADS)

    Sadeghi, S.; Emami, M. R.

    2018-04-01

    This paper studies an auroral event using data from three spacecraft of the Cluster mission, one inside and two at the poleward edge of the bottom of the Auroral Acceleration Region (AAR). The study reveals the three-dimensional profile of the region's poleward boundary, showing spatial segmentation of the electric potential structures and their decay in time. It also depicts localized magnetic field variations and field-aligned currents that appear to have remained stable for at least 80 s. Such observations became possible due to the fortuitous motion of the three spacecraft nearly parallel to each other and tangential to the AAR edge, so that the differences and variations can be seen when the spacecraft enter and exit the segmentations, hence revealing their position with respect to the AAR.

  1. The growing pipeline of natural aminoacyl-tRNA synthetase inhibitors for malaria treatment

    PubMed Central

    Saint-Léger, Adélaïde; Sinadinos, Christopher; Ribas de Pouplana, Lluís

    2016-01-01

    ABSTRACT Malaria remains a major global health problem. Parasite resistance to existing drugs makes development of new antimalarials an urgency. The protein synthesis machinery is an excellent target for the development of new anti-infectives, and aminoacyl-tRNA synthetases (aaRS) have been validated as antimalarial drug targets. However, avoiding the emergence of drug resistance and improving selectivity to target aaRS in apicomplexan parasites, such as Plasmodium falciparum, remain crucial challenges. Here we discuss such issues using examples of known inhibitors of P. falciparum aaRS, namely halofuginone, cladosporin and borrelidin (inhibitors of ProRS, LysRS and ThrRS, respectively). Encouraging recent results provide useful guidelines to facilitate the development of novel drug candidates which are more potent and selective against these essential enzymes. PMID:26963157

  2. Exploring Multitarget Interactions to Reduce Opiate Withdrawal Syndrome and Psychiatric Comorbidity

    PubMed Central

    2013-01-01

    Opioid addiction is often characterized as a chronic relapsing condition due to the severe somatic and behavioral signs, associated with depressive disorders, triggered by opiate withdrawal. Since prolonged abstinence remains a major challenge, our interest has been addressed to such objective. Exploring multitarget interactions, the present investigation suggests that 3 or its (S)-enantiomer and 4, endowed with effective α2C-AR agonism/α2A-AR antagonism/5-HT1A-R agonism, or 7 and 9–11 producing efficacious α2C-AR agonism/α2A-AR antagonism/I2–IBS interaction might represent novel multifunctional tools potentially useful for reducing withdrawal syndrome and associated depression. Such agents, lacking in sedative side effects due to their α2A-AR antagonism, might afford an improvement over current therapies with clonidine-like drugs. PMID:24900763

  3. A Survey of Serious Aircraft Accidents Involving Fatigue Fracture. Volume 1. Fixed-Wing Aircraft (Etude sur des Accidents Importants d’Avions du aux Effets des Fractures de Fatigue. Volume 1. Effets sur des Avions).

    DTIC Science & Technology

    1983-04-01

    Bureau of Standards. NTS3 National Transportation Safety Board (USA). NTSB AAR NTSB Aircraft Accident Report. NZ AAR New Zealand Aircraft Accident Report...NZ AI New Zealand Accident Investigation Bureau. 0 -5- RAN Royal Australian Navy RAAI Royal Australian Air Force RAF Royal Air Force, UK S Substantial...Ice land Iraq Ireland Jamaica (1966 -1981) Japan (1973 - Feb. 81) Kenya Lethoso Malaysia Ma law i Mal ta Mexico Netherlands New Zealand Norway

  4. Technology Assessment of the DACS/MERADCOM Prestaged Ammunition Loading System (PALS) Concept Study.

    DTIC Science & Technology

    1980-08-01

    American Railroads (AAR) and Coast 1-2 Arthurl) little.lnc - Guard (CC) regulations for the shipment of ammunition. The system must be compatible with...to meet Association of American Railroads (AAR) and Coast Guard (CC) regulations for the shipment of ammunition. The system must be compatible with...unloaded u ler field conditions? (4) Can the PALS meet AA and CC regulations for the safe shipment of ammunition in commercial cargo containers? (5

  5. Ridge Tectonics, Magma Supply, and Ridge-Hotpot Interaction at the Eastern End of the Australian-Antarctic Ridge

    NASA Astrophysics Data System (ADS)

    Kim, S.; Lin, J.; Park, S.; Choi, H.; Lee, S.

    2013-12-01

    During 2011-2013 the Korea Polar Research Institute (KOPRI) conducted three successive expeditions to the eastern end of the Australian-Antarctic Ridge (AAR) to investigate the tectonics, geochemistry, and hydrothermal activity of this intermediate fast spreading system. On board the Korean icebreaker R/V Araon, the science party collected multiple types of data including multibeam bathymetry, gravity, magnetics, as well as rock and water column samples. In addition, Miniature Autonomous Plume Recorders (MAPRs) were deployed at each of the wax-core rock sampling sites to detect the presence of active hydrothermal vents. In this study, we present a detailed analysis of a 360-km-long super-segment at the eastern end of the AAR to quantify the spatial variations in ridge morphology and investigate its respond to changes in melt supply. The study region contains several intriguing bathymetric features including (1) abrupt changes in the axial topography, alternating between rift valleys and axial highs within relatively short ridge segments; (2) overshooting ridge tips at the ridge-transform intersections; (3) systematic migration patterns of hooked ridges; (4) a 350-km-long mega-transform fault; and (5) robust axial and off-axis volcanisms. To obtain a proxy for regional variations in magma supply, we calculated residual mantle Bouguer gravity anomalies (RMBA), gravity-derived crustal thickness, and residual topography for seven sub-segments. The results of the analyses revealed that the southern flank of the AAR is associated with a shallower seafloor, more negative RMBA, thicker crust, and/or less dense mantle than the conjugate northern flank. Furthermore, this N-S asymmetry becomes more prominent toward the super-segment of the AAR. Such regional variations in seafloor topography and RMBA are consistent with the hypothesis that ridge segments in the study area have interacted with the Balleny hotspot, currently lies southwest of the AAR. However, the influence of

  6. Biodistribution and Safety Assessment of Bladder Cancer Specific Recombinant Oncolytic Adenovirus in Subcutaneous Xenografts Tumor Model in Nude Mice

    PubMed Central

    Wang, Fang; Wang, Zhiping; Tian, Hongwei; Qi, Meijiao; Zhai, Zhenxing; Li, Shuwen; Li, Renju; Zhang, Hongjuan; Wang, Wenyun; Fu, Shenjun; Lu, Jianzhong; Rodriguez, Ronald; Guo, Yinglu; Zhou, Liqun

    2012-01-01

    Background The previous works about safety evaluation for constructed bladder tissue specific adenovirus are poorly documented. Thus, we investigated the biodistribution and body toxicity of bladder specific oncolytic adenovirus Ad-PSCAE-UPII-E1A (APU-E1A) and Ad-PSCAE-UPII-E1A-AR (APU-E1A-AR), providing meaningful information prior to embarking on human clinical trials. Materials and Method Conditionally replicate recombinant adenovirus (CRADs) APU-E1A, APU-EIA-AR were constructed with bladder tissue specific Uroplakin II (UP II) promoter to induce the expression of Ad5E1A gene and E1A-AR fusing gene, and PSCAE was inserted at upstream of promoter to enhance the function of promoter. Based on the cytopathic and anti-tumor effect of bladder cancer, these CRADs were intratumorally injected into subcutaneous xenografts tumor in nude mice. We then determined the toxicity through general health and behavioral assessment, hepatic and hematological toxicity evaluation, macroscopic and microscopic postmortem analyses. The spread of the transgene E1A of adenovirus was detected with RT-PCR and Western blot. Virus replication and distribution were examined with APU-LUC administration and Luciferase Assay. Results General assessment and body weight of the animals did not reveal any alteration in general behavior. The hematological alterations of groups which were injected with 5×108 pfu or higher dose (5×109 pfu) of APU-E1A and APU-E1A-AR showed no difference in comparison with PBS group, and only slight increased transaminases in contrast to PBS group at 5×109 pfu of APU-E1A and APU-E1A-AR were observed. E1A transgene did not disseminate to organs outside of xenograft tumor. Virus replication was not detected in other organs beside tumor according to Luciferase Assay. Conclusions Our study showed that recombinant adenovirus APU-E1A-AR and APU-E1A appear safe with 5×107 pfu and 5×108 pfu intratumorally injection in mice, without any discernable effects on general health

  7. Biodistribution and safety assessment of bladder cancer specific recombinant oncolytic adenovirus in subcutaneous xenografts tumor model in nude mice.

    PubMed

    Wang, Fang; Wang, Zhiping; Tian, Hongwei; Qi, Meijiao; Zhai, Zhenxing; Li, Shuwen; Li, Renju; Zhang, Hongjuan; Wang, Wenyun; Fu, Shenjun; Lu, Jianzhong; Rodriguez, Ronald; Guo, Yinglu; Zhou, Liqun

    2012-04-01

    The previous works about safety evaluation for constructed bladder tissue specific adenovirus are poorly documented. Thus, we investigated the biodistribution and body toxicity of bladder specific oncolytic adenovirus Ad-PSCAE-UPII-E1A (APU-E1A) and Ad-PSCAE-UPII-E1A-AR (APU-E1A-AR), providing meaningful information prior to embarking on human clinical trials. Conditionally replicate recombinant adenovirus (CRADs) APU-E1A, APU-EIA-AR were constructed with bladder tissue specific UroplakinII(UPII) promoter to induce the expression of Ad5E1A gene and E1A-AR fusing gene, and PSCAE was inserted at upstream of promoter to enhance the function of promoter. Based on the cytopathic and anti-tumor effect of bladder cancer, these CRADs were intratumorally injected into subcutaneous xenografts tumor in nude mice. We then determined the toxicity through general health and behavioral assessment, hepatic and hematological toxicity evaluation, macroscopic and microscopic postmortem analyses. The spread of the transgene E1A of adenovirus was detected with RT-PCR and Western blot. Virus replication and distribution were examined with APU-LUC administration and Luciferase Assay. General assessment and body weight of the animals did not reveal any alteration in general behavior. The hematological alterations of groups which were injected with 5x10(8) pfu or higher dose (5x10(9) pfu) of APU-E1A and APU-E1A-AR showed no difference in comparison with PBS group, and only slight increased transaminases in contrast to PBS group at 5x10(9) pfu of APU-E1A and APU-E1A-AR were observed. E1A transgene did not disseminate to organs outside of xenograft tumor. Virus replication was not detected in other organs beside tumor according to Luciferase Assay. Our study showed that recombinant adenovirus APU-E1A-AR and APU-E1A appear safe with 5x10(7) pfu and 5x10(8) pfu intratumorally injection in mice, without any discernable effects on general health and behavior.

  8. Attenuation of alpha2A-adrenergic receptor expression in neonatal rat brain by RNA interference or antisense oligonucleotide reduced anxiety in adulthood.

    PubMed

    Shishkina, G T; Kalinina, T S; Dygalo, N N

    2004-01-01

    Brain alpha2-adrenergic receptors (alpha2-ARs) have been implicated in the regulation of anxiety, which is associated with stress. Environmental treatments during neonatal development could modulate the level of brain alpha2-AR expression and alter anxiety in adults, suggesting possible involvement of these receptors in early-life programming of anxiety state. The present study was undertaken to determine whether the reduction of the expression of A subtype of these receptors most abundant in the neonatal brain affects anxiety-related behavior in adulthood. We attenuated the expression of alpha2A-ARs during neonatal life by two different sequence specific approaches, antisense technology and RNA interference. Treatment of rats with the antisense oligodeoxynucleotide or short interfering RNA (siRNA) against alpha2A-ARs on the days 2-4 of their life, produced a marked acute decrease in the levels of both alpha2A-AR mRNA and [3H]RX821002 binding sites in the brainstem into which drugs were injected. The decrease of alpha2A-AR expression in the neonatal brainstem influenced the development of this receptor system in the brain regions as evidenced by the increased number of [3H]RX821002 binding sites in the hypothalamus of adult animals with both neonatal alpha2A-AR knockdown treatments; also in the frontal cortex of antisense-treated, and in the hippocampus of siRNA-treated adult rats. These adult animals also demonstrated a decreased anxiety in the elevated plus-maze as evidenced by an increased number of the open arm entries, greater proportion of time spent in the open arms, and more than a two-fold increase in the number of exploratory head dips. The results provide the first evidence that the reduction in the brain expression of a gene encoding for alpha2A-AR during neonatal life led to the long-term neurochemical and behavioral alterations. The data suggests that alterations in the expression of the receptor-specific gene during critical periods of brain

  9. When Will We Ever Learn? The After Action Review, Lessons Learned and the Next Steps in Training and Educating the Homeland Security Enterprise for the 21st Century

    DTIC Science & Technology

    2013-06-01

    Evaluation Program (HSEEP), Volume III, February 2007, 27. 29 Ibid., 4. 30 Ibid. 12 …allows players to engage in a self -assessment of their...be correct in one respect. A 2003 paper entitled A Comparative Study of the After Action Review (AAR) in the Context of the Southern Africa Crisis...A Comparative Study of the After Action Review (AAR) in the Context of the Southern Africa Crisis, June 2003. 46 Ibid. 47 Human Factors Integration

  10. Functional Dissection of the Bipartite Active Site of the Class I Coenzyme A (CoA)-Transferase Succinyl-CoA:Acetate CoA-Transferase.

    PubMed

    Murphy, Jesse R; Mullins, Elwood A; Kappock, T Joseph

    2016-01-01

    Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates <3 Å apart. In this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes and orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analog dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analog of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. The ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA.

  11. Functional Dissection of the Bipartite Active Site of the Class I Coenzyme A (CoA)-Transferase Succinyl-CoA:Acetate CoA-Transferase

    PubMed Central

    Murphy, Jesse R.; Mullins, Elwood A.; Kappock, T. Joseph

    2016-01-01

    Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates <3 Å apart. In this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes and orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analog dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analog of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. The ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA. PMID:27242998

  12. Automatic localization of IASLC-defined mediastinal lymph node stations on CT images using fuzzy models

    NASA Astrophysics Data System (ADS)

    Matsumoto, Monica M. S.; Beig, Niha G.; Udupa, Jayaram K.; Archer, Steven; Torigian, Drew A.

    2014-03-01

    Lung cancer is associated with the highest cancer mortality rates among men and women in the United States. The accurate and precise identification of the lymph node stations on computed tomography (CT) images is important for staging disease and potentially for prognosticating outcome in patients with lung cancer, as well as for pretreatment planning and response assessment purposes. To facilitate a standard means of referring to lymph nodes, the International Association for the Study of Lung Cancer (IASLC) has recently proposed a definition of the different lymph node stations and zones in the thorax. However, nodal station identification is typically performed manually by visual assessment in clinical radiology. This approach leaves room for error due to the subjective and potentially ambiguous nature of visual interpretation, and is labor intensive. We present a method of automatically recognizing the mediastinal IASLC-defined lymph node stations by modifying a hierarchical fuzzy modeling approach previously developed for body-wide automatic anatomy recognition (AAR) in medical imagery. Our AAR-lymph node (AAR-LN) system follows the AAR methodology and consists of two steps. In the first step, the various lymph node stations are manually delineated on a set of CT images following the IASLC definitions. These delineations are then used to build a fuzzy hierarchical model of the nodal stations which are considered as 3D objects. In the second step, the stations are automatically located on any given CT image of the thorax by using the hierarchical fuzzy model and object recognition algorithms. Based on 23 data sets used for model building, 22 independent data sets for testing, and 10 lymph node stations, a mean localization accuracy of within 1-6 voxels has been achieved by the AAR-LN system.

  13. Automated Quantification of Myocardial Salvage in a Rat Model of Ischemia–Reperfusion Injury Using 3D High‐Resolution Magnetic Resonance Imaging (MRI)

    PubMed Central

    Grieve, Stuart M.; Mazhar, Jawad; Callaghan, Fraser; Kok, Cindy Y.; Tandy, Sarah; Bhindi, Ravinay; Figtree, Gemma A.

    2014-01-01

    Background Quantification of myocardial “area at risk” (AAR) and myocardial infarction (MI) zone is critical for assessing novel therapies targeting myocardial ischemia–reperfusion (IR) injury. Current “gold‐standard” methods perfuse the heart with Evan's Blue and stain with triphenyl tetrazolium chloride (TTC), requiring manual slicing and analysis. We aimed to develop and validate a high‐resolution 3‐dimensional (3D) magnetic resonance imaging (MRI) method for quantifying MI and AAR. Methods and Results Forty‐eight hours after IR was induced, rats were anesthetized and gadopentetate dimeglumine was administered intravenously. After 10 minutes, the coronary artery was re‐ligated and a solution containing iron oxide microparticles and Evan's Blue was infused (for comparison). Hearts were harvested and transversally sectioned for TTC staining. Ex vivo MR images of slices were acquired on a 9.4‐T magnet. T2* data allowed visualization of AAR, with microparticle‐associated signal loss in perfused regions. T1 data demonstrated gadolinium retention in infarcted zones. Close correlation (r=0.92 to 0.94; P<0.05) of MRI and Evan's Blue/TTC measures for both AAR and MI was observed when the combined techniques were applied to the same heart slice. However, 3D MRI acquisition and analysis of whole heart reduced intra‐observer variability compared to assessment of isolated slices, and allowed automated segmentation and analysis, thus reducing interobserver variation. Anatomical resolution of 81 μm3 was achieved (versus ≈2 mm with manual slicing). Conclusions This novel, yet simple, MRI technique allows precise assessment of infarct and AAR zones. It removes the need for tissue slicing and provides opportunity for 3D digital analysis at high anatomical resolution in a streamlined manner accessible for all laboratories already performing IR experiments. PMID:25146703

  14. Accuracy of Area at Risk Quantification by Cardiac Magnetic Resonance According to the Myocardial Infarction Territory.

    PubMed

    Fernández-Friera, Leticia; García-Ruiz, José Manuel; García-Álvarez, Ana; Fernández-Jiménez, Rodrigo; Sánchez-González, Javier; Rossello, Xavier; Gómez-Talavera, Sandra; López-Martín, Gonzalo J; Pizarro, Gonzalo; Fuster, Valentín; Ibáñez, Borja

    2017-05-01

    Area at risk (AAR) quantification is important to evaluate the efficacy of cardioprotective therapies. However, postinfarction AAR assessment could be influenced by the infarcted coronary territory. Our aim was to determine the accuracy of T 2 -weighted short tau triple-inversion recovery (T 2 W-STIR) cardiac magnetic resonance (CMR) imaging for accurate AAR quantification in anterior, lateral, and inferior myocardial infarctions. Acute reperfused myocardial infarction was experimentally induced in 12 pigs, with 40-minute occlusion of the left anterior descending (n = 4), left circumflex (n = 4), and right coronary arteries (n = 4). Perfusion CMR was performed during selective intracoronary gadolinium injection at the coronary occlusion site (in vivo criterion standard) and, additionally, a 7-day CMR, including T 2 W-STIR sequences, was performed. Finally, all animals were sacrificed and underwent postmortem Evans blue staining (classic criterion standard). The concordance between the CMR-based criterion standard and T 2 W-STIR to quantify AAR was high for anterior and inferior infarctions (r = 0.73; P = .001; mean error = 0.50%; limits = -12.68%-13.68% and r = 0.87; P = .001; mean error = -1.5%; limits = -8.0%-5.8%, respectively). Conversely, the correlation for the circumflex territories was poor (r = 0.21, P = .37), showing a higher mean error and wider limits of agreement. A strong correlation between pathology and the CMR-based criterion standard was observed (r = 0.84, P < .001; mean error = 0.91%; limits = -7.55%-9.37%). T 2 W-STIR CMR sequences are accurate to determine the AAR for anterior and inferior infarctions; however, their accuracy for lateral infarctions is poor. These findings may have important implications for the design and interpretation of clinical trials evaluating the effectiveness of cardioprotective therapies. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  15. Geophysical Characteristics of the Australian-Antarctic Ridge

    NASA Astrophysics Data System (ADS)

    Kim, S. S.; Lin, J.; Park, S. H.; Choi, H.; Lee, S. M.

    2014-12-01

    Between 2011 and 2013, the Korea Polar Research Institute (KOPRI) conducted three consecutive geologic surveys at the little explored eastern ends of the Australian-Antarctic Ridge (AAR) to characterize the tectonics, geochemistry, and hydrothermal activity of this intermediate spreading system. Using the Korean icebreaker R/V Araon, the multi-disciplinary research team collected bathymetry, gravity, magnetics, and rock and water column samples. In addition, Miniature Autonomous Plume Recorders (MAPRs) were deployed at wax-core rock sampling sites to detect the presence of active hydrothermal vents. Here we present a detailed analysis of a 300-km-long supersegment of the AAR to quantify the spatial variations in ridge morphology and robust axial and off-axis volcanisms. The ridge axis morphology alternates between rift valleys and axial highs within relatively short ridge segments. To obtain a geological proxy for regional variations in magma supply, we calculated residual mantle Bouguer gravity anomalies (RMBA), gravity-derived crustal thickness, and residual topography for seven sub-segments. The results of the analyses revealed that the southern flank of the AAR is associated with shallower seafloor, more negative RMBA, thicker crust, and/or less dense mantle than the conjugate northern flank. Furthermore, this north-south asymmetry becomes more prominent toward the KR1 supersegment of the AAR. The axial topography of the KR1 supersegment exhibits a sharp transition from axial highs at the western end to rift valleys at the eastern end, with regions of axial highs being associated with more magma supply as indicated by more negative RMBA. We also compare and contrast the characteristics of the AAR supersegment with that of other ridges of intermediate spreading rates, including the Juan de Fuca Ridge, Galápagos Spreading Center, and Southeast Indian Ridge west of the Australian-Antarctic Discordance, to investigate the influence of ridge-hotspot interaction on

  16. Functional dissection of the bipartite active site of the class I coenzyme A (CoA)-transferase succinyl-CoA:acetate CoA-transferase

    DOE PAGES

    Murphy, Jesse R.; Mullins, Elwood A.; Kappock, T. Joseph

    2016-05-23

    Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates <3 Å apart. Here in this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes andmore » orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analog dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analog of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. Finally, the ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA.« less

  17. α(2A)-adrenergic receptors filter parabrachial inputs to the bed nucleus of the stria terminalis.

    PubMed

    Flavin, Stephanie A; Matthews, Robert T; Wang, Qin; Muly, E Chris; Winder, Danny G

    2014-07-09

    α2-adrenergic receptors (AR) within the bed nucleus of the stria terminalis (BNST) reduce stress-reward interactions in rodent models. In addition to their roles as autoreceptors, BNST α(2A)-ARs suppress glutamatergic transmission. One prominent glutamatergic input to the BNST originates from the parabrachial nucleus (PBN) and consists of asymmetric axosomatic synapses containing calcitonin gene-related peptide (CGRP) and vGluT2. Here we provide immunoelectron microscopic data showing that many asymmetric axosomatic synapses in the BNST contain α(2A)-ARs. Further, we examined optically evoked glutamate release ex vivo in BNST from mice with virally delivered channelrhodopsin2 (ChR2) expression in PBN. In BNST from these animals, ChR2 partially colocalized with CGRP, and activation generated EPSCs in dorsal anterolateral BNST neurons that elicited two cell-type-specific outcomes: (1) feedforward inhibition or (2) an EPSP that elicited firing. We found that the α(2A)-AR agonist guanfacine selectively inhibited this PBN input to the BNST, preferentially reducing the excitatory response in ex vivo mouse brain slices. To begin to assess the overall impact of α(2A)-AR control of this PBN input on BNST excitatory transmission, we used a Thy1-COP4 mouse line with little postsynaptic ChR2 expression nor colocalization of ChR2 with CGRP in the BNST. In slices from these mice, we found that guanfacine enhanced, rather than suppressed, optogenetically initiated excitatory drive in BNST. Thus, our study reveals distinct actions of PBN afferents within the BNST and suggests that α(2A)-AR agonists may filter excitatory transmission in the BNST by inhibiting a component of the PBN input while enhancing the actions of other inputs. Copyright © 2014 the authors 0270-6474/14/349319-13$15.00/0.

  18. Positron emission tomography (PET) imaging of prostate cancer with a gastrin releasing peptide receptor antagonist--from mice to men.

    PubMed

    Wieser, Gesche; Mansi, Rosalba; Grosu, Anca L; Schultze-Seemann, Wolfgang; Dumont-Walter, Rebecca A; Meyer, Philipp T; Maecke, Helmut R; Reubi, Jean Claude; Weber, Wolfgang A

    2014-01-01

    Ex vivo studies have shown that the gastrin releasing peptide receptor (GRPr) is overexpressed on almost all primary prostate cancers, making it a promising target for prostate cancer imaging and targeted radiotherapy. Biodistribution, dosimetry and tumor uptake of the GRPr antagonist ⁶⁴Cu-CB-TE2A-AR06 [(⁶⁴Cu-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)-PEG₄-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-LeuNH₂] were studied by PET/CT in four patients with newly diagnosed prostate cancer (T1c-T2b, Gleason 6-7). No adverse events were observed after injection of ⁶⁴Cu-CB-TE2A-AR06. Three of four tumors were visualized with high contrast [tumor-to-prostate ratio > 4 at 4 hours (h) post injection (p.i.)], one small tumor (T1c, < 5% tumor on biopsy specimens) showed moderate contrast (tumor-to-prostate ratio at 4 h: 1.9). Radioactivity was cleared by the kidneys and only the pancreas demonstrated significant accumulation of radioactivity, which rapidly decreased over time. ⁶⁴Cu-CB-TE2A-AR06 shows very favorable characteristics for imaging prostate cancer. Future studies evaluating ⁶⁴Cu-CB-TE2A-AR06 PET/CT for prostate cancer detection, staging, active surveillance, and radiation treatment planning are necessary.

  19. Probing catalytic rate enhancement during intramembrane proteolysis.

    PubMed

    Arutyunova, Elena; Smithers, Cameron C; Corradi, Valentina; Espiritu, Adam C; Young, Howard S; Tieleman, D Peter; Lemieux, M Joanne

    2016-09-01

    Rhomboids are ubiquitous intramembrane serine proteases involved in various signaling pathways. While the high-resolution structures of the Escherichia coli rhomboid GlpG with various inhibitors revealed an active site comprised of a serine-histidine dyad and an extensive oxyanion hole, the molecular details of rhomboid catalysis were unclear because substrates are unknown for most of the family members. Here we used the only known physiological pair of AarA rhomboid with its psTatA substrate to decipher the contribution of catalytically important residues to the reaction rate enhancement. An MD-refined homology model of AarA was used to identify residues important for catalysis. We demonstrated that the AarA active site geometry is strict and intolerant to alterations. We probed the roles of H83 and N87 oxyanion hole residues and determined that substitution of H83 either abolished AarA activity or reduced the transition state stabilization energy (ΔΔG‡) by 3.1 kcal/mol; substitution of N87 decreased ΔΔG‡ by 1.6-3.9 kcal/mol. Substitution M154, a residue conserved in most rhomboids that stabilizes the catalytic general base, to tyrosine, provided insight into the mechanism of nucleophile generation for the catalytic dyad. This study provides a quantitative evaluation of the role of several residues important for hydrolytic efficiency and oxyanion stabilization during intramembrane proteolysis.

  20. Automatic anatomy recognition on CT images with pathology

    NASA Astrophysics Data System (ADS)

    Huang, Lidong; Udupa, Jayaram K.; Tong, Yubing; Odhner, Dewey; Torigian, Drew A.

    2016-03-01

    Body-wide anatomy recognition on CT images with pathology becomes crucial for quantifying body-wide disease burden. This, however, is a challenging problem because various diseases result in various abnormalities of objects such as shape and intensity patterns. We previously developed an automatic anatomy recognition (AAR) system [1] whose applicability was demonstrated on near normal diagnostic CT images in different body regions on 35 organs. The aim of this paper is to investigate strategies for adapting the previous AAR system to diagnostic CT images of patients with various pathologies as a first step toward automated body-wide disease quantification. The AAR approach consists of three main steps - model building, object recognition, and object delineation. In this paper, within the broader AAR framework, we describe a new strategy for object recognition to handle abnormal images. In the model building stage an optimal threshold interval is learned from near-normal training images for each object. This threshold is optimally tuned to the pathological manifestation of the object in the test image. Recognition is performed following a hierarchical representation of the objects. Experimental results for the abdominal body region based on 50 near-normal images used for model building and 20 abnormal images used for object recognition show that object localization accuracy within 2 voxels for liver and spleen and 3 voxels for kidney can be achieved with the new strategy.

  1. Carcass and meat quality of Assaf milk fed lambs: Effect of rearing system and sex.

    PubMed

    Rodríguez, A B; Landa, R; Bodas, R; Prieto, N; Mantecón, A R; Giráldez, F J

    2008-10-01

    The effect of sex and rearing system on growth and carcass and meat characteristics of milk fed Assaf lambs was studied. Thirty-six lambs, 18 males and 18 females were used. Twelve lambs remained with their mothers throughout the experiment (NR). Within 24-36h of birth, the rest were housed individually and fed twice a day ad libitum (AAR) or at 70% of ad libitum consumption (RAR) with reconstituted cow's milk. Sex did not affect animal performance, yet females showed higher carcass and non-carcass fat deposits. NR lambs showed greater BWG than AAR fed lambs, and AAR, higher than the RAR. Differences between naturally and artificially reared lambs in CCW and killing out percentage were not significant. Empty digestive tract and mesenteric fat weights were greater for RAR than NR lambs, with the AAR lambs demonstrating intermediate values; conversely, omental fat was greater in NR lambs. Carcass ether extract content was greater for NR lambs, possibly due to the greater growth. Use of ad libitum cow's milk substitute in suckling lambs twice a day resulted in less body weight gain but similar killing out percentages compared to naturally raised lambs. A 70% restricted supply increased the days in suckling and reduced carcass fatness and compactness. Except for water loss, which was less in NR than artificially fed lambs, no differences were found in meat characteristics.

  2. Backbone Brackets and Arginine Tweezers delineate Class I and Class II aminoacyl tRNA synthetases

    PubMed Central

    Haupt, V. Joachim; Schroeder, Michael; Labudde, Dirk

    2018-01-01

    The origin of the machinery that realizes protein biosynthesis in all organisms is still unclear. One key component of this machinery are aminoacyl tRNA synthetases (aaRS), which ligate tRNAs to amino acids while consuming ATP. Sequence analyses revealed that these enzymes can be divided into two complementary classes. Both classes differ significantly on a sequence and structural level, feature different reaction mechanisms, and occur in diverse oligomerization states. The one unifying aspect of both classes is their function of binding ATP. We identified Backbone Brackets and Arginine Tweezers as most compact ATP binding motifs characteristic for each Class. Geometric analysis shows a structural rearrangement of the Backbone Brackets upon ATP binding, indicating a general mechanism of all Class I structures. Regarding the origin of aaRS, the Rodin-Ohno hypothesis states that the peculiar nature of the two aaRS classes is the result of their primordial forms, called Protozymes, being encoded on opposite strands of the same gene. Backbone Brackets and Arginine Tweezers were traced back to the proposed Protozymes and their more efficient successors, the Urzymes. Both structural motifs can be observed as pairs of residues in contemporary structures and it seems that the time of their addition, indicated by their placement in the ancient aaRS, coincides with the evolutionary trace of Proto- and Urzymes. PMID:29659563

  3. Quantification of myocardial area at risk in the absence of collateral flow: the validation of angiographic scores by myocardial perfusion single-photon emission computed tomography.

    PubMed

    Rodríguez-Palomares, José F; Alonso, Albert; Martí, Gerard; Aguadé-Bruix, Santiago; González-Alujas, M T; Romero-Farina, Guillermo; Candell-Riera, Jaume; García del Blanco, Bruno; Evangelista, Artur; García-Dorado, David

    2013-02-01

    Our study aimed to compare the area at risk (AAR) determined by single-photon emission computed tomography (SPECT) with the Bypass Angioplasty Revascularization Investigation (BARI) and modified Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) angiographic scores in the setting of patients undergoing coronary angioplasty for either unstable angina or an STEMI. Radionuclide myocardial perfusion imaging prior to reperfusion has classically been the most widely practised technique for assessing the AAR and has been successfully used to compare the efficacy of various reperfusion strategies in patients with an ST-segment elevation myocardial infarction (STEMI). The BARI and modified APPROACH scores are angiographic methods widely used to provide a rapid estimation of the AAR; however, they have not been directly validated with myocardial perfusion single-photon emission computed tomography (SPECT). Fifty-five patients with no previous myocardial infarction who underwent coronary angioplasty for single-vessel disease (unstable angina: n = 25 or an STEMI: n = 30) with no evidence of collaterals (Rentrop Collateral Score <2) were included in a prospective study. In STEMI patients, the (99m)Tc-tetrofosmin was injected prior to opening of the occluded vessel and, in patients with unstable angina after 10-15 seconds of balloon inflation. Acquisition was performed with a dual-head gammacamera with a low-energy and high-resolution collimator. A total of 60 projections were acquired using a non-circular orbit. No attenuation or scatter correction was used. Maximal contours of hypoperfusion regions corresponding to each coronary artery occlusion were delineated over a polar map of 17 segments and compared with the estimated AAR determined by two experienced interventional cardiologists using both angiographic scores. Mean AAR percentage in SPECT was 35.0 (10.0%-56.0%). A high correlation was found between BARI and APPROACH scores (r = 0.9, P

  4. Opportunities Missed: A Cross-Sectional Survey of the Provision of Smoking Cessation Care to Pregnant Women by Australian General Practitioners and Obstetricians.

    PubMed

    Zeev, Yael Bar; Bonevski, Billie; Twyman, Laura; Watt, Kerrianne; Atkins, Lou; Palazzi, Kerrin; Oldmeadow, Christopher; Gould, Gillian S

    2017-05-01

    Similar to other high-income countries, smoking rates in pregnancy can be high in specific vulnerable groups in Australia. Several clinical guidelines exist, including the 5A's (Ask, Advice, Assess, Assist, and Arrange), ABCD (Ask, Brief advice, Cessation, and Discuss), and AAR (Ask, Advice, and Refer). There is lack of data on provision of smoking cessation care (SCC) of Australian General Practitioners (GPs) and Obstetricians. A cross-sectional survey explored the provision of SCC, barriers and enablers using the Theoretical Domains Framework, and the associations between them. Two samples were invited: (1) GPs and Obstetricians from a college database (n = 5571); (2) GPs from a special interest group for Indigenous health (n = 500). Dimension reduction for the Theoretical Domains Framework was achieved with factor analysis. Logistic regression was carried out for performing all the 5A's and the AAR. Performing all of the 5A's, ABCD, and AAR "often and always" was reported by 19.9%, 15.6%, and 49.2% respectively. "Internal influences" (such as confidence in counselling) were associated with higher performance of the 5A's (Adjusted OR 2.69 (95% CI 1.5, 4.8), p < .001), whereas "External influences" (such as workplace routine) were associated with higher performance of AAR (Adjusted OR 1.7 (95% CI 1, 2.8), p = .035). Performance in providing SCC to pregnant women is low among Australian GPs and Obstetricians. Training clinicians should focus on improving internal influences such as confidence and optimism. The AAR may be easier to implement, and interventions at the service level should focus on ensuring easy, effective, and acceptable referral mechanisms are in place. Improving provision of the 5A's approach should focus on the individual level, including better training for GPs and Obstetricians, designed to improve specific "internal" barriers such as confidence in counselling and optimism. The AAR may be easier to implement in view of the higher overall

  5. Tobacco users' perceptions of a brief tobacco cessation intervention in community pharmacies.

    PubMed

    Patwardhan, Pallavi D; Chewning, Betty A

    2010-01-01

    To explore factors affecting tobacco users' perceived appropriateness of a brief and proactive tobacco cessation counseling program, ask, advise, and refer (AAR), at community pharmacies. Inductive thematic analysis. Southern Wisconsin during fall 2008. 24 tobacco users who had recently received brief and proactive tobacco cessation counseling at a community pharmacy. Semistructured telephone interviews conducted by primary author. Perceptions of a brief and proactive tobacco cessation counseling program conducted at community pharmacies. In conducting the thematic analysis, eight distinct themes were identified. Display of information and resources at pharmacies for use by tobacco users as needed was identified as the most predominant theme and was found to be most helpful by many respondents. Other themes identified in decreasing order of prevalence were: tobacco users' perceptions of the role of pharmacists in health care, tobacco users' belief that smoking could interact with a current medication or health condition, tobacco users' sensitivity toward their tobacco use behavior or being told what to do, nonconfrontational and friendly approach of pharmacists, tobacco users' readiness to quit at the time of AAR counseling, tobacco user initiation of tobacco use discussion, and tobacco users' belief that tobacco use is bad. Overall, this qualitative investigation suggests that several factors might influence tobacco users' perceived appropriateness of AAR counseling at community pharmacies. AAR might be well received by tobacco users and pharmacy patrons as long as it is done in a professional and respectful manner.

  6. Automatic anatomy recognition using neural network learning of object relationships via virtual landmarks

    NASA Astrophysics Data System (ADS)

    Yan, Fengxia; Udupa, Jayaram K.; Tong, Yubing; Xu, Guoping; Odhner, Dewey; Torigian, Drew A.

    2018-03-01

    The recently developed body-wide Automatic Anatomy Recognition (AAR) methodology depends on fuzzy modeling of individual objects, hierarchically arranging objects, constructing an anatomy ensemble of these models, and a dichotomous object recognition-delineation process. The parent-to-offspring spatial relationship in the object hierarchy is crucial in the AAR method. We have found this relationship to be quite complex, and as such any improvement in capturing this relationship information in the anatomy model will improve the process of recognition itself. Currently, the method encodes this relationship based on the layout of the geometric centers of the objects. Motivated by the concept of virtual landmarks (VLs), this paper presents a new one-shot AAR recognition method that utilizes the VLs to learn object relationships by training a neural network to predict the pose and the VLs of an offspring object given the VLs of the parent object in the hierarchy. We set up two neural networks for each parent-offspring object pair in a body region, one for predicting the VLs and another for predicting the pose parameters. The VL-based learning/prediction method is evaluated on two object hierarchies involving 14 objects. We utilize 54 computed tomography (CT) image data sets of head and neck cancer patients and the associated object contours drawn by dosimetrists for routine radiation therapy treatment planning. The VL neural network method is found to yield more accurate object localization than the currently used simple AAR method.

  7. Insulin-Increased L-Arginine Transport Requires A2A Adenosine Receptors Activation in Human Umbilical Vein Endothelium

    PubMed Central

    Guzmán-Gutiérrez, Enrique; Westermeier, Francisco; Salomón, Carlos; González, Marcelo; Pardo, Fabián; Leiva, Andrea; Sobrevia, Luis

    2012-01-01

    Adenosine causes vasodilation of human placenta vasculature by increasing the transport of arginine via cationic amino acid transporters 1 (hCAT-1). This process involves the activation of A2A adenosine receptors (A2AAR) in human umbilical vein endothelial cells (HUVECs). Insulin increases hCAT-1 activity and expression in HUVECs, and A2AAR stimulation increases insulin sensitivity in subjects with insulin resistance. However, whether A2AAR plays a role in insulin-mediated increase in L-arginine transport in HUVECs is unknown. To determine this, we first assayed the kinetics of saturable L-arginine transport (1 minute, 37°C) in the absence or presence of nitrobenzylthioinosine (NBTI, 10 µmol/L, adenosine transport inhibitor) and/or adenosine receptors agonist/antagonists. We also determined hCAT-1 protein and mRNA expression levels (Western blots and quantitative PCR), and SLC7A1 (for hCAT-1) reporter promoter activity. Insulin and NBTI increased the extracellular adenosine concentration, the maximal velocity for L-arginine transport without altering the apparent K m for L-arginine transport, hCAT-1 protein and mRNA expression levels, and SLC7A1 transcriptional activity. An A2AAR antagonist ZM-241385 blocked these effects. ZM241385 inhibited SLC7A1 reporter transcriptional activity to the same extent in cells transfected with pGL3-hCAT-1−1606 or pGL3-hCAT-1−650 constructs in the presence of NBTI + insulin. However, SLC7A1 reporter activity was increased by NBTI only in cells transfected with pGL3-hCAT-1−1606, and the ZM-241385 sensitive fraction of the NBTI response was similar in the absence or in the presence of insulin. Thus, insulin modulation of hCAT-1 expression and activity requires functional A2AAR in HUVECs, a mechanism that may be applicable to diseases associated with fetal insulin resistance, such as gestational diabetes. PMID:22844517

  8. δ-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) mediate intermittent hypoxia induced protection of canine myocardium.

    PubMed

    Estrada, Juan A; Williams, Arthur G; Sun, Jie; Gonzalez, Leticia; Downey, H Fred; Caffrey, James L; Mallet, Robert T

    2016-03-01

    Intermittent, normobaric hypoxia confers robust cardioprotection against ischemia-induced myocardial infarction and lethal ventricular arrhythmias. δ-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) have been implicated in cardioprotective phenomena, but their roles in intermittent hypoxia are unknown. This study examined the contributions of DOR and ROS in mediating intermittent hypoxia-induced cardioprotection. Mongrel dogs completed a 20 day program consisting of 5-8 daily, 5-10 min cycles of moderate, normobaric hypoxia (FIO2 0.095-0.10), with intervening 4 min room air exposures. Subsets of dogs received the DOR antagonist naltrindole (200 μg/kg, sc) or antioxidant N-acetylcysteine (250 mg/kg, po) before each hypoxia session. Twenty-four hours after the last session, the left anterior descending coronary artery was occluded for 60 min and then reperfused for 5 h. Arrhythmias detected by electrocardiography were scored according to the Lambeth II conventions. Left ventricles were sectioned and stained with 2,3,5-triphenyl-tetrazolium-chloride, and infarct sizes were expressed as percentages of the area at risk (IS/AAR). Intermittent hypoxia sharply decreased IS/AAR from 41 ± 5 % (n = 12) to 1.8 ± 0.9 % (n = 9; P < 0.001) and arrhythmia score from 4.1 ± 0.3 to 0.7 ± 0.2 (P < 0.001) vs. non-hypoxic controls. Naltrindole (n = 6) abrogated the cardioprotection with IS/AAR 35 ± 5 % and arrhythmia score 3.7 ± 0.7 (P < 0.001 vs. untreated intermittent hypoxia). N-acetylcysteine (n = 6) interfered to a similar degree, with IS/AAR 42 ± 3 % and arrhythmia score 4.7 ± 0.3 (P < 0.001 vs. untreated intermittent hypoxia). Without the intervening reoxygenations, hypoxia (n = 4) was not cardioprotective (IS/AAR 50 ± 8 %; arrhythmia score 4.5 ± 0.5; P < 0.001 vs. intermittent hypoxia). Thus DOR, ROS and cyclic reoxygenation were obligatory participants in the gradually evolving cardioprotection produced by intermittent hypoxia.

  9. Adaptive Aggregation Routing to Reduce Delay for Multi-Layer Wireless Sensor Networks

    PubMed Central

    Li, Xujing; Xie, Mande; Zeng, Zhiwen; Cai, Zhiping

    2018-01-01

    The quality of service (QoS) regarding delay, lifetime and reliability is the key to the application of wireless sensor networks (WSNs). Data aggregation is a method to effectively reduce the data transmission volume and improve the lifetime of a network. In the previous study, a common strategy required that data wait in the queue. When the length of the queue is greater than or equal to the predetermined aggregation threshold (Nt) or the waiting time is equal to the aggregation timer (Tt), data are forwarded at the expense of an increase in the delay. The primary contributions of the proposed Adaptive Aggregation Routing (AAR) scheme are the following: (a) the senders select the forwarding node dynamically according to the length of the data queue, which effectively reduces the delay. In the AAR scheme, the senders send data to the nodes with a long data queue. The advantages are that first, the nodes with a long data queue need a small amount of data to perform aggregation; therefore, the transmitted data can be fully utilized to make these nodes aggregate. Second, this scheme balances the aggregating and data sending load; thus, the lifetime increases. (b) An improved AAR scheme is proposed to improve the QoS. The aggregation deadline (Tt) and the aggregation threshold (Nt) are dynamically changed in the network. In WSNs, nodes far from the sink have residual energy because these nodes transmit less data than the other nodes. In the improved AAR scheme, the nodes far from the sink have a small value of Tt and Nt to reduce delay, and the nodes near the sink are set to a large value of Tt and Nt to reduce energy consumption. Thus, the end to end delay is reduced, a longer lifetime is achieved, and the residual energy is fully used. Simulation results demonstrate that compared with the previous scheme, the performance of the AAR scheme is improved. This scheme reduces the delay by 14.91%, improves the lifetime by 30.91%, and increases energy efficiency by 76

  10. Body-wide hierarchical fuzzy modeling, recognition, and delineation of anatomy in medical images.

    PubMed

    Udupa, Jayaram K; Odhner, Dewey; Zhao, Liming; Tong, Yubing; Matsumoto, Monica M S; Ciesielski, Krzysztof C; Falcao, Alexandre X; Vaideeswaran, Pavithra; Ciesielski, Victoria; Saboury, Babak; Mohammadianrasanani, Syedmehrdad; Sin, Sanghun; Arens, Raanan; Torigian, Drew A

    2014-07-01

    To make Quantitative Radiology (QR) a reality in radiological practice, computerized body-wide Automatic Anatomy Recognition (AAR) becomes essential. With the goal of building a general AAR system that is not tied to any specific organ system, body region, or image modality, this paper presents an AAR methodology for localizing and delineating all major organs in different body regions based on fuzzy modeling ideas and a tight integration of fuzzy models with an Iterative Relative Fuzzy Connectedness (IRFC) delineation algorithm. The methodology consists of five main steps: (a) gathering image data for both building models and testing the AAR algorithms from patient image sets existing in our health system; (b) formulating precise definitions of each body region and organ and delineating them following these definitions; (c) building hierarchical fuzzy anatomy models of organs for each body region; (d) recognizing and locating organs in given images by employing the hierarchical models; and (e) delineating the organs following the hierarchy. In Step (c), we explicitly encode object size and positional relationships into the hierarchy and subsequently exploit this information in object recognition in Step (d) and delineation in Step (e). Modality-independent and dependent aspects are carefully separated in model encoding. At the model building stage, a learning process is carried out for rehearsing an optimal threshold-based object recognition method. The recognition process in Step (d) starts from large, well-defined objects and proceeds down the hierarchy in a global to local manner. A fuzzy model-based version of the IRFC algorithm is created by naturally integrating the fuzzy model constraints into the delineation algorithm. The AAR system is tested on three body regions - thorax (on CT), abdomen (on CT and MRI), and neck (on MRI and CT) - involving a total of over 35 organs and 130 data sets (the total used for model building and testing). The training and

  11. Storm-associated Alfvén Waves in the Polar Environment

    NASA Astrophysics Data System (ADS)

    Keiling, A.; Wygant, J. R.; Dombeck, J. P.

    2017-12-01

    Global polar distribution maps of Alfvénic Poynting flux and Alfvén-wave-accelerated electrons now exist from a number of satellites, orbiting at various altitudes, including below and in the auroral acceleration region (AAR), above the AAR and in the equatorial plasma sheet. Together with auroral images, it has been established that the nightside aurora, in particular its premidnight to midnight dominance, is coupled to these waves. Moreover, global simulations have reproduced the observed nightside distribution of Alfvén waves, coming from the far-tail magnetospheric dynamo. While recent studies, using low-altitude and equatorial satellites, have shown a deviation from this average nightside pattern during storm times, as of now there is no such study to provide the link between these regions, namely just above the AAR. In this presentation, we will present Polar spacecraft-based data during storm times, covering the altitude range from 4 to 7 RE (geocentric distance) and spanning a time period of six years. The results will be put in context to published studies, in particular with regard to morphology and dissipation.

  12. Automated Aerial Refueling Hitches a Ride on AFF

    NASA Technical Reports Server (NTRS)

    Hansen, Jennifer L.; Murray, James E.; Bever, Glenn; Campos, Norma V.; Schkolnik, Gerard

    2007-01-01

    The recent introduction of uninhabited aerial vehicles [UAVs (basically, remotely piloted or autonomous aircraft)] has spawned new developments in autonomous operation and posed new challenges. Automated aerial refueling (AAR) is a capability that will enable UAVs to travel greater distances and loiter longer over targets. NASA Dryden Flight Research Center, in cooperation with the Defense Advanced Research Projects Agency (DARPA), the Naval Air Systems Command (NAVAIR), the Naval Air Force Pacific Fleet, and the Air Force Research Laboratory, rapidly conceived and accomplished an AAR flight research project focused on collecting a unique, high-quality database on the dynamics of the hose and drogue of an aerial refueling system. This flight-derived database would be used to validate mathematical models of the dynamics in support of design and analysis of AAR systems for future UAVs. The project involved the use of two Dryden F/A-18 airplanes and an S-3 hose-drogue refueling store on loan from the Navy. In this year-long project, which was started on October 1, 2002, 583 research maneuvers were completed during 23 flights.

  13. Adaptive Aggregation Routing to Reduce Delay for Multi-Layer Wireless Sensor Networks.

    PubMed

    Li, Xujing; Liu, Anfeng; Xie, Mande; Xiong, Neal N; Zeng, Zhiwen; Cai, Zhiping

    2018-04-16

    The quality of service (QoS) regarding delay, lifetime and reliability is the key to the application of wireless sensor networks (WSNs). Data aggregation is a method to effectively reduce the data transmission volume and improve the lifetime of a network. In the previous study, a common strategy required that data wait in the queue. When the length of the queue is greater than or equal to the predetermined aggregation threshold ( N t ) or the waiting time is equal to the aggregation timer ( T t ), data are forwarded at the expense of an increase in the delay. The primary contributions of the proposed Adaptive Aggregation Routing (AAR) scheme are the following: (a) the senders select the forwarding node dynamically according to the length of the data queue, which effectively reduces the delay. In the AAR scheme, the senders send data to the nodes with a long data queue. The advantages are that first, the nodes with a long data queue need a small amount of data to perform aggregation; therefore, the transmitted data can be fully utilized to make these nodes aggregate. Second, this scheme balances the aggregating and data sending load; thus, the lifetime increases. (b) An improved AAR scheme is proposed to improve the QoS. The aggregation deadline ( T t ) and the aggregation threshold ( N t ) are dynamically changed in the network. In WSNs, nodes far from the sink have residual energy because these nodes transmit less data than the other nodes. In the improved AAR scheme, the nodes far from the sink have a small value of T t and N t to reduce delay, and the nodes near the sink are set to a large value of T t and N t to reduce energy consumption. Thus, the end to end delay is reduced, a longer lifetime is achieved, and the residual energy is fully used. Simulation results demonstrate that compared with the previous scheme, the performance of the AAR scheme is improved. This scheme reduces the delay by 14.91%, improves the lifetime by 30.91%, and increases energy

  14. U-Series Disequilibria across the New Southern Ocean Mantle Province, Australian-Antarctic Ridge

    NASA Astrophysics Data System (ADS)

    Scott, S. R.; Sims, K. W. W.; Park, S. H.; Langmuir, C. H.; Lin, J.; Kim, S. S.; Blichert-Toft, J.; Michael, P. J.; Choi, H.; Yang, Y. S.

    2017-12-01

    Mid-ocean ridge basalts (MORB) provide a unique window into the temporal and spatial scales of mantle evolution. Long-lived radiogenic isotopes in MORB have demonstrated that the mantle contains many different chemical components or "flavors". U-series disequilibria in MORB have further shown that different chemical components/lithologies in the mantle contribute differently to mantle melting processes beneath mid-ocean ridges. Recent Sr, Nd, Hf, and Pb isotopic analyses from newly collected basalts along the Australian-Antarctic Ridge (AAR) have revealed that a large distinct mantle province exists between the Australian-Antarctic Discordance and the Pacific-Antarctic Ridge, extending from West Antarctica and Marie Byrd Land to New Zealand and Eastern Australia (Park et al., submitted). This southern mantle province is located between the Indian-type mantle and the Pacific-type mantle domains. U-series measurements in the Southeast Indian Ridge and East Pacific Rise provinces show distinct signatures suggestive of differences in melting processes and source lithology. To examine whether the AAR mantle province also exhibits different U-series systematics we have measured U-Th-Ra disequilibria data on 38 basalts from the AAR sampled along 500 km of ridge axis from two segments that cross the newly discovered Southern Ocean Mantle province. We compare the data to those from nearby ridge segments show that the AAR possesses unique U-series disequilibria, and are thus undergoing distinct mantle melting dynamics relative to the adjacent Pacific and Indian ridges. (230Th)/(238U) excesses in zero-age basalts (i.e., those with (226Ra)/(230Th) > 1.0) range from 1.3 to 1.7, while (226Ra)/(230Th) ranges from 1.0 to 2.3. (226Ra)/(230Th) and (230Th)/(238U) are negatively correlated, consistent with the model of mixing between deep and shallow melts. The AAR data show higher values of disequilibria compared to the Indian and Pacific Ridges, which can be explained by either

  15. Ask-Advise-Connect: a new approach to smoking treatment delivery in health care settings.

    PubMed

    Vidrine, Jennifer Irvin; Shete, Sanjay; Cao, Yumei; Greisinger, Anthony; Harmonson, Penny; Sharp, Barry; Miles, Lyndsay; Zbikowski, Susan M; Wetter, David W

    2013-03-25

    Several national health care-based smoking cessation initiatives have been recommended to facilitate the delivery of evidence-based treatments, such as quitline (telephone-based tobacco cessation services) assistance. The most notable examples are the 5 As (Ask, Advise, Assess, Assist, Arrange) and Ask. Advise. Refer. (AAR) programs. Unfortunately, rates of primary care referrals to quitlines are low, and most referred smokers fail to call for assistance. To evaluate a new approach--Ask-Advise-Connect (AAC)--designed to address barriers to linking smokers with treatment. A pair-matched, 2-treatment-arm, group-randomized design in 10 family practice clinics in a single metropolitan area. Five clinics were randomized to the AAC (intervention) and 5 to the AAR (control) conditions. In both conditions, clinic staff were trained to assess and record the smoking status of all patients at all visits in the electronic health record, and smokers were given brief advice to quit. In the AAC clinics, the names and telephone numbers of smokers who agreed to be connected were sent electronically to the quitline daily, and patients were called proactively by the quitline within 48 hours. In the AAR clinics, smokers were offered a quitline referral card and encouraged to call on their own. All data were collected from February 8 through December 27, 2011. Ten clinics in Houston, Texas. Smoking status assessments were completed for 42,277 patients; 2052 unique smokers were identified at AAC clinics, and 1611 smokers were identified at AAR clinics. Linking smokers with quitline-delivered treatment. Impact was based on the RE-AIM (Reach, Efficacy, Adoption, Implementation, and Maintenance) conceptual framework and defined as the proportion of all identified smokers who enrolled in treatment. In the AAC clinics, 7.8% of all identified smokers enrolled in treatment vs 0.6% in the AAR clinics (t4 = 9.19 [P < .001]; odds ratio, 11.60 [95% CI, 5.53-24.32]), a 13-fold increase in the

  16. GPS navigation algorithms for Autonomous Airborne Refueling of Unmanned Air Vehicles

    NASA Astrophysics Data System (ADS)

    Khanafseh, Samer Mahmoud

    Unmanned Air Vehicles (UAVs) have recently generated great interest because of their potential to perform hazardous missions without risking loss of life. If autonomous airborne refueling is possible for UAVs, mission range and endurance will be greatly enhanced. However, concerns about UAV-tanker proximity, dynamic mobility and safety demand that the relative navigation system meets stringent requirements on accuracy, integrity, and continuity. In response, this research focuses on developing high-performance GPS-based navigation architectures for Autonomous Airborne Refueling (AAR) of UAVs. The AAR mission is unique because of the potentially severe sky blockage introduced by the tanker. To address this issue, a high-fidelity dynamic sky blockage model was developed and experimentally validated. In addition, robust carrier phase differential GPS navigation algorithms were derived, including a new method for high-integrity reacquisition of carrier cycle ambiguities for recently-blocked satellites. In order to evaluate navigation performance, world-wide global availability and sensitivity covariance analyses were conducted. The new navigation algorithms were shown to be sufficient for turn-free scenarios, but improvement in performance was necessary to meet the difficult requirements for a general refueling mission with banked turns. Therefore, several innovative methods were pursued to enhance navigation performance. First, a new theoretical approach was developed to quantify the position-domain integrity risk in cycle ambiguity resolution problems. A mechanism to implement this method with partially-fixed cycle ambiguity vectors was derived, and it was used to define tight upper bounds on AAR navigation integrity risk. A second method, where a new algorithm for optimal fusion of measurements from multiple antennas was developed, was used to improve satellite coverage in poor visibility environments such as in AAR. Finally, methods for using data-link extracted

  17. Prior automatic posture and activity identification improves physical activity energy expenditure prediction from hip-worn triaxial accelerometry.

    PubMed

    Garnotel, M; Bastian, T; Romero-Ugalde, H M; Maire, A; Dugas, J; Zahariev, A; Doron, M; Jallon, P; Charpentier, G; Franc, S; Blanc, S; Bonnet, S; Simon, C

    2018-03-01

    Accelerometry is increasingly used to quantify physical activity (PA) and related energy expenditure (EE). Linear regression models designed to derive PAEE from accelerometry-counts have shown their limits, mostly due to the lack of consideration of the nature of activities performed. Here we tested whether a model coupling an automatic activity/posture recognition (AAR) algorithm with an activity-specific count-based model, developed in 61 subjects in laboratory conditions, improved PAEE and total EE (TEE) predictions from a hip-worn triaxial-accelerometer (ActigraphGT3X+) in free-living conditions. Data from two independent subject groups of varying body mass index and age were considered: 20 subjects engaged in a 3-h urban-circuit, with activity-by-activity reference PAEE from combined heart-rate and accelerometry monitoring (Actiheart); and 56 subjects involved in a 14-day trial, with PAEE and TEE measured using the doubly-labeled water method. PAEE was estimated from accelerometry using the activity-specific model coupled to the AAR algorithm (AAR model), a simple linear model (SLM), and equations provided by the companion-software of used activity-devices (Freedson and Actiheart models). AAR-model predictions were in closer agreement with selected references than those from other count-based models, both for PAEE during the urban-circuit (RMSE = 6.19 vs 7.90 for SLM and 9.62 kJ/min for Freedson) and for EE over the 14-day trial, reaching Actiheart performances in the latter (PAEE: RMSE = 0.93 vs. 1.53 for SLM, 1.43 for Freedson, 0.91 MJ/day for Actiheart; TEE: RMSE = 1.05 vs. 1.57 for SLM, 1.70 for Freedson, 0.95 MJ/day for Actiheart). Overall, the AAR model resulted in a 43% increase of daily PAEE variance explained by accelerometry predictions. NEW & NOTEWORTHY Although triaxial accelerometry is widely used in free-living conditions to assess the impact of physical activity energy expenditure (PAEE) on health, its precision and accuracy are often debated

  18. Body-wide anatomy recognition in PET/CT images

    NASA Astrophysics Data System (ADS)

    Wang, Huiqian; Udupa, Jayaram K.; Odhner, Dewey; Tong, Yubing; Zhao, Liming; Torigian, Drew A.

    2015-03-01

    With the rapid growth of positron emission tomography/computed tomography (PET/CT)-based medical applications, body-wide anatomy recognition on whole-body PET/CT images becomes crucial for quantifying body-wide disease burden. This, however, is a challenging problem and seldom studied due to unclear anatomy reference frame and low spatial resolution of PET images as well as low contrast and spatial resolution of the associated low-dose CT images. We previously developed an automatic anatomy recognition (AAR) system [15] whose applicability was demonstrated on diagnostic computed tomography (CT) and magnetic resonance (MR) images in different body regions on 35 objects. The aim of the present work is to investigate strategies for adapting the previous AAR system to low-dose CT and PET images toward automated body-wide disease quantification. Our adaptation of the previous AAR methodology to PET/CT images in this paper focuses on 16 objects in three body regions - thorax, abdomen, and pelvis - and consists of the following steps: collecting whole-body PET/CT images from existing patient image databases, delineating all objects in these images, modifying the previous hierarchical models built from diagnostic CT images to account for differences in appearance in low-dose CT and PET images, automatically locating objects in these images following object hierarchy, and evaluating performance. Our preliminary evaluations indicate that the performance of the AAR approach on low-dose CT images achieves object localization accuracy within about 2 voxels, which is comparable to the accuracies achieved on diagnostic contrast-enhanced CT images. Object recognition on low-dose CT images from PET/CT examinations without requiring diagnostic contrast-enhanced CT seems feasible.

  19. Both alpha(1A)- and alpha(1B)-adrenergic receptors crosstalk to down regulate beta(1)-ARs in mouse heart: coupling to differential PTX-sensitive pathways.

    PubMed

    Rorabaugh, Boyd R; Gaivin, Robert J; Papay, Robert S; Shi, Ting; Simpson, Paul C; Perez, Dianne M

    2005-11-01

    Adrenergic receptors (ARs) play an important role in the regulation of cardiac function. Cardiac inotropy is primarily regulated by beta(1)-ARs. However, alpha(1)-ARs may play an important role in inotropy during heart failure. Previous work has suggested that the alpha(1B)-AR modulates beta(1)-AR function in the heart. The potential role of the alpha(1A)-AR has not been previously studied. We used transgenic mice that express constitutively active mutant (CAM) forms of the alpha(1A)-AR or alpha(1B)-AR regulated by their endogenous promoters. Expression of the CAM alpha(1A)-AR or CAM alpha(1B)-AR had no effect on basal cardiac function (developed pressure, +dP/dT, -dP/dT, heart rate, flow rate). However, both alpha(1)-AR subtypes significantly decreased isoproterenol-stimulated +dP/dT. Pertussis toxin had no effect on +dP/dT in CAM alpha(1A)-AR hearts but restored +dP/dT to non-transgenic values in CAM alpha(1B)-AR hearts. Radioligand binding indicated a selective decrease in the density of beta(1)-ARs in both CAM mice. However, G-proteins, cAMP, or the percentage of high and low affinity states were unchanged in either transgenic compared with control. These data demonstrate that CAM alpha(1A)- and alpha(1B)-ARs both down regulate beta(1)-AR-mediated inotropy in the mouse heart. However, alpha(1)-AR subtypes are coupled to different beta-AR mediated signaling pathways with the alpha(1B)-AR being pertussis toxin sensitive.

  20. Mantle structure beneath Africa and Arabia from adaptively parameterized P-wave tomography: Implications for the origin of Cenozoic Afro-Arabian tectonism

    NASA Astrophysics Data System (ADS)

    Hansen, Samantha E.; Nyblade, Andrew A.; Benoit, Margaret H.

    2012-02-01

    While the Cenozoic Afro-Arabian Rift System (AARS) has been the focus of numerous studies, it has long been questioned if low-velocity anomalies in the upper mantle beneath eastern Africa and western Arabia are connected, forming one large anomaly, and if any parts of the anomalous upper mantle structure extend into the lower mantle. To address these questions, we have developed a new image of P-wave velocity variations in the Afro-Arabian mantle using an adaptively parameterized tomography approach and an expanded dataset containing travel-times from earthquakes recorded on many new temporary and permanent seismic networks. Our model shows a laterally continuous, low-velocity region in the upper mantle beneath all of eastern Africa and western Arabia, extending to depths of ~ 500-700 km, as well as a lower mantle anomaly beneath southern Africa that rises from the core-mantle boundary to at least ~ 1100 km depth and possibly connects to the upper mantle anomaly across the transition zone. Geodynamic models which invoke one or more discrete plumes to explain the origin of the AARS are difficult to reconcile with the lateral and depth extent of the upper mantle low-velocity region, as are non-plume models invoking small-scale convection passively induced by lithospheric extension or by edge-flow around thick cratonic lithosphere. Instead, the low-velocity anomaly beneath the AARS can be explained by the African superplume model, where the anomalous upper mantle structure is a continuation of a large, thermo-chemical upwelling in the lower mantle beneath southern Africa. These findings provide further support for a geodynamic connection between processes in Earth's lower mantle and continental break-up within the AARS.

  1. Orientation-dependent potential of mean force for protein folding

    NASA Astrophysics Data System (ADS)

    Mukherjee, Arnab; Bhimalapuram, Prabhakar; Bagchi, Biman

    2005-07-01

    We present a solvent-implicit minimalistic model potential among the amino acid residues of proteins, obtained by using the known native structures [deposited in the Protein Data Bank (PDB)]. In this model, the amino acid side chains are represented by a single ellipsoidal site, defined by the group of atoms about the center of mass of the side chain. These ellipsoidal sites interact with other sites through an orientation-dependent interaction potential which we construct in the following fashion. First, the site-site potential of mean force (PMF) between heavy atoms is calculated [following F. Melo and E. Feytsman, J. Mol. Biol. 267, 207 (1997)] from statistics of their distance separation obtained from crystal structures. These site-site potentials are then used to calculate the distance and the orientation-dependent potential between side chains of all the amino acid residues (AAR). The distance and orientation dependencies show several interesting results. For example, we find that the PMF between two hydrophobic AARs, such as phenylalanine, is strongly attractive at short distances (after the obvious repulsive region at very short separation) and is characterized by a deep minimum, for specific orientations. For the interaction between two hydrophilic AARs, such a deep minimum is absent and in addition, the potential interestingly reveals the combined effect of polar (charge) and hydrophobic interactions among some of these AARs. The effectiveness of our potential has been tested by calculating the Z-scores for a large set of proteins. The calculated Z-scores show high negative values for most of them, signifying the success of the potential to identify the native structure from among a large number of its decoy states.

  2. Amino acid starvation sensing dampens IL-1β production by activating riboclustering and autophagy

    PubMed Central

    Battu, Srikanth; Afroz, Sumbul; Giddaluru, Jeevan; Naz, Saima; Huang, Weishan; Khumukcham, Saratchandra Singh; Khan, Rafiq Ahmad; Bhat, Saleem Yousuf; Qureshi, Insaf Ahmed; Manavathi, Bramanandam; Khan, Aleem Ahmed; August, Avery; Hasnain, Seyed Ehtesham; Khan, Nooruddin

    2018-01-01

    Activation of the amino acid starvation response (AAR) increases lifespan and acute stress resistance as well as regulates inflammation. However, the underlying mechanisms remain unclear. Here, we show that activation of AAR pharmacologically by Halofuginone (HF) significantly inhibits production of the proinflammatory cytokine interleukin 1β (IL-1β) and provides protection from intestinal inflammation in mice. HF inhibits IL-1β through general control nonderepressible 2 kinase (GCN2)–dependent activation of the cytoprotective integrated stress response (ISR) pathway, resulting in rerouting of IL-1β mRNA from translationally active polysomes to inactive ribocluster complexes—such as stress granules (SGs)—via recruitment of RNA-binding proteins (RBPs) T cell–restricted intracellular antigen-1(TIA-1)/TIA-1–related (TIAR), which are further cleared through induction of autophagy. GCN2 ablation resulted in reduced autophagy and SG formation, which is inversely correlated with IL-1β production. Furthermore, HF diminishes inflammasome activation through suppression of reactive oxygen species (ROS) production. Our study unveils a novel mechanism by which IL-1β is regulated by AAR and further suggests that administration of HF might offer an effective therapeutic intervention against inflammatory diseases. PMID:29621237

  3. Alanyl-tRNA synthetase mutation in a family with dominant distal hereditary motor neuropathy

    PubMed Central

    Zhao, Z.; Hashiguchi, A.; Sakiyama, Y.; Okamoto, Y.; Tokunaga, S.; Zhu, L.; Shen, H.; Takashima, H.

    2012-01-01

    Objective: To identify a new genetic cause of distal hereditary motor neuropathy (dHMN), which is also known as a variant of Charcot-Marie-Tooth disease (CMT), in a Chinese family. Methods: We investigated a Chinese family with dHMN clinically, electrophysiologically, and genetically. We screened for the mutations of 28 CMT or related pathogenic genes using an originally designed microarray resequencing DNA chip. Results: Investigation of the family history revealed an autosomal dominant transmission pattern. The clinical features of the family included mild weakness and wasting of the distal muscles of the lower limb and foot deformity, without clinical sensory involvement. Electrophysiologic studies revealed motor neuropathy. MRI of the lower limbs showed accentuated fatty infiltration of the gastrocnemius and vastus lateralis muscles. All 4 affected family members had a heterozygous missense mutation c.2677G>A (p.D893N) of alanyl-tRNA synthetase (AARS), which was not found in the 4 unaffected members and control subjects. Conclusion: An AARS mutation caused dHMN in a Chinese family. AARS mutations result in not only a CMT phenotype but also a dHMN phenotype. PMID:22573628

  4. Atlantoaxial Rotatory Subluxation: A Review for the Pediatric Emergency Physician.

    PubMed

    Kinon, Merritt D; Nasser, Rani; Nakhla, Jonathan; Desai, Rupen; Moreno, Jessica R; Yassari, Reza; Bagley, Carlos A

    2016-10-01

    Pediatric emergency physicians must have a high clinical suspicion for atlantoaxial rotatory subluxation (AARS), particularly when a child presents with neck pain and an abnormal head posture without the ability to return to a neutral position. As shown in the neurosurgical literature, timely diagnosis and swift initiation of treatment have a greater chance of treatment success for the patient. However, timely treatment is complicated because torticollis can result from a variety of maladies, including: congenital abnormalities involving the C1-C2 joint or the surrounding supporting muscles and ligaments, central nervous system abnormalities, obstetric palsies from brachial plexus injuries, clavicle fractures, head and neck surgery, and infection. The treating pediatrician must discern the etiology of the underlying problem to determine both timing and treatment paradigms, which vary widely between these illnesses. We present a comprehensive review of AARS that is intended for pediatric emergency physicians. Management of AARS can vary widely bases on factors, such as duration of symptoms, as well as the patient's history. The goal of this review is to streamline the management paradigms and provide an inclusive review for pediatric emergency first responders.

  5. All-cancers mortality rates approaching diseases of the heart mortality rates as leading cause of death in Texas.

    PubMed

    Wyatt, Stephen W; Maynard, William Ryan; Risser, David R; Hakenewerth, Anne M; Williams, Melanie A; Garcia, Rebecca

    2014-01-01

    Diseases of the heart and malignant neoplasms (all-cancers) are the leading causes of death in the United States. The gap between the two has been closing in recent years. To assess the gap status in Texas and to establish a baseline to support evaluation efforts for the Cancer Prevention Research Institute of Texas, mortality data from 2006 to 2009 were analyzed. Immediate cause of death data in Texas for the years 2006-2009 were analyzed and rates developed by sex, race/ethnicity, and four metropolitan counties. Overall, for the years 2006-2009, the age-adjusted mortality rates (AARs) among Texas residents for both diseases of the heart and all-cancers decreased; however, during this time frame, there was greater improvement in diseases of the heart AARs as compared with all-cancers AARs. For the four large metropolitan counties of Bexar, Dallas, Harris, and Travis, data were analyzed by sex and race/ethnicity, and 11 of the 12 largest percent mortality rate decreases were for diseases of the heart. Age-adjusted mortality rates among Texas residents from diseases of the heart are showing improvement as compared with the rates for all-cancers.

  6. Structural basis of Brr2-Prp8 interactions and implications for U5 snRNP biogenesis and the spliceosome active site.

    PubMed

    Nguyen, Thi Hoang Duong; Li, Jade; Galej, Wojciech P; Oshikane, Hiroyuki; Newman, Andrew J; Nagai, Kiyoshi

    2013-06-04

    The U5 small nuclear ribonucleoprotein particle (snRNP) helicase Brr2 disrupts the U4/U6 small nuclear RNA (snRNA) duplex and allows U6 snRNA to engage in an intricate RNA network at the active center of the spliceosome. Here, we present the structure of yeast Brr2 in complex with the Jab1/MPN domain of Prp8, which stimulates Brr2 activity. Contrary to previous reports, our crystal structure and mutagenesis data show that the Jab1/MPN domain binds exclusively to the N-terminal helicase cassette. The residues in the Jab1/MPN domain, whose mutations in human Prp8 cause the degenerative eye disease retinitis pigmentosa, are found at or near the interface with Brr2, clarifying its molecular pathology. In the cytoplasm, Prp8 forms a precursor complex with U5 snRNA, seven Smproteins, Snu114, and Aar2, but after nuclear import, Brr2 replaces Aar2 to form mature U5 snRNP. Our structure explains why Aar2 and Brr2 are mutually exclusive and provides important insights into the assembly of U5 snRNP.

  7. Parallel loss of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases and mtDNA-encoded tRNAs in Cnidaria.

    PubMed

    Haen, Karri M; Pett, Walker; Lavrov, Dennis V

    2010-10-01

    Unlike most animal mitochondrial (mt) genomes, which encode a set of 22 transfer RNAs (tRNAs) sufficient for mt protein synthesis, those of cnidarians have only retained one or two tRNA genes. Whether the missing cnidarian mt-tRNA genes relocated outside the main mt chromosome or were lost remains unclear. It is also unknown what impact the loss of tRNA genes had on other components of the mt translational machinery. Here, we explored the nuclear genome of the cnidarian Nematostella vectensis for the presence of mt-tRNA genes and their corresponding mt aminoacyl-tRNA synthetases (mt-aaRS). We detected no candidates for mt-tRNA genes and only two mt-aaRS orthologs. At the same time, we found that all but one cytosolic aaRS appear to be targeted to mitochondria. These results indicate that the loss of mt-tRNAs in Cnidaria is genuine and occurred in parallel with the loss of nuclear-encoded mt-aaRS. Our phylogenetic analyses of individual aaRS revealed that although the nearly total loss of mt-aaRS is rare, aaRS gene deletion and replacement have occurred throughout the evolution of Metazoa.

  8. Integrated Battlefield Effects Research for the National Training Center. Appendix E. Requirements Design Specification and Demonstration Report for the Exercise Coordination and Control (ECC) Demonstration System

    DTIC Science & Technology

    1984-12-31

    mode 3. Edit AAR mode 4. Run AR mode Each of the modes shall be mutually eclusive. In the real-time mode, the station tactical display shall reflect...periods of the exercise segment. The edit AAR mode shall provide the operator with the capability of creating/ editing a command file for use during an...II .,II IH 0 - hUi I -24 .6d, -I" @ 0 M% A A a a dJ a) 6 I I - -- a’ 1.* % 46- 8 ’ 0 "S 8 -- -- "- - I .-36 aISa "S-a:z:-a I I b 0 Il -- I -- I1 -I

  9. Salivary alpha amylase in on-call from home fire and emergency service personnel.

    PubMed

    Hall, Sarah J; Aisbett, Brad; Robertson, Samuel J; Ferguson, Sally A; Turner, Anne I

    2017-11-01

    The effect of working on-call from home on the sympatho-adrenal medullary system activity is currently unknown. This study had two aims, Aim 1: examine salivary alpha amylase awakening response (AAR) and diurnal salivary alpha amylase (sAA) profile in fire and emergency service workers who operate on-call from home following a night on-call with a call (NIGHT-CALL), a night on-call without a call (NO-CALL) and an off-call night (OFF-CALL), and Aim 2: explore whether there was an anticipatory effect of working on-call from home (ON) compared to when there was an off-call (OFF) on the diurnal sAA profile. Participants wore activity monitors, completed sleep and work diaries and collected seven saliva samples a day for one week. AAR area under the curve with respect to ground (AUC G ), AAR area under the curve with respect to increase (AUC I ), AAR reactivity, diurnal sAA slope, diurnal sAA AUC G and mean 12-h sAA concentrations were calculated. Separate generalised estimating equation models were constructed for each variable of interest for each aim. For Aim 1, there were no differences between NIGHT-CALL or NO-CALL and OFF-CALL for any response variable. For Aim 2, there was no difference between any response variable of interest when ON the following night compared to when OFF the following night ( n  = 14). These findings suggest that there is no effect of working on-call from home on sAA, but should be interpreted with caution, as overnight data were not collected. Future research, using overnight heart rate monitoring, could help confirm these findings. © 2017 The authors.

  10. Rocketdyne RBCC Engine Concept Development

    NASA Technical Reports Server (NTRS)

    Ratckin, G.; Goldman, A.; Ortwerth, P.; Weisberg, S.

    1999-01-01

    Boeing Rocketdyne is pursuing the development of Rocket Based Combined Cycle (RBCC), propulsion systems as demonstrated by significant contract work in the hypersonic arena (ART, NASP, SCT, system studies) and over 12 years of steady company discretionary investment. The Rocketdyne concept is a fixed geometry integrated rocket, ramjet, scramjet which is hydrogen fueled and uses hydrogen regenerative cooling. The baseline engine structural configuration uses an integral structure that eliminates panel seals. seal purge gas, and closeout side attachments. Rocketdyne's experimental RBCC engine (Engine A5) was constructed under contract with the NASA Marshall Space Flight Center. Engine A5 models the complete flight engine flowpath consisting of an inlet, isolator, airbreathing combustor and nozzle. High performance rocket thrusters are integrated into the engine to enable both air-augmented rocket (AAR) and pure rocket operation. Engine A5 was tested in CASL's new FAST facility as an air-augmented rocket, a ramjet and a pure rocket. Measured performance demonstrated vision vehicle performance levels for Mach 3 AAR operation and ramjet operation from Mach 3 to 4. Rocket mode performance was above predictions. For the first time. testing also demonstrated transition from AAR operation to ramjet operation. This baseline configuration has also been shown, in previous testing, to perform well in the scramjet mode.

  11. The DarkSide physics program and its recent results

    DOE PAGES

    D'Angelo, D.

    2017-01-12

    Here, DarkSide (DS) at Gran Sasso underground laboratory is a direct Dark Matter search program based on Time Projection Chambers (TPC) with liquid Argon from underground sources. The DarkSide-50 (DS-50) TPC, with 150 kg of Argon is installed inside active neutron and muon detectors. DS-50 has been taking data since November 2013 with Atmospheric Argon (AAr) and since April 2015 with Underground Argon (UAr), depleted in radioactive 39Ar by a factor ~1400. The exposure of 1422 kg d of AAr has demonstrated that the operation of DS-50 for three years in a background free condition is a solid reality, thanksmore » to the superb performance of the Pulse Shape Analysis. The first release of results from an exposure of 2616 kg d of UAr has shown no candidate Dark Matter events. We have set the best limit for Spin-Independent elastic nuclear scattering of WIMPs obtained by Argon-based detectors, corresponding to a cross-section of 2 10 –44 cm 2 at a WIMP mass of 100 GeV. We present the detector design and performance, the results from the AAr run and the first results from the UAr run and we briefly introduce the future of the DarkSide program.« less

  12. The DarkSide physics program and its recent results

    NASA Astrophysics Data System (ADS)

    D'Angelo, D.; Agnes, P.; Agostino, L.; F. M. Albuquerque, I.; Alexander, T.; K. Alton, A.; Arisaka, K.; Back, H. O.; Baldin, B.; Biery, K.; Bonfini, G.; Bossa, M.; Bottino, B.; Brigatti, A.; Brodsky, J.; Budano, F.; Bussino, S.; Cadeddu, M.; Cadonati, L.; Cadoni, M.; Calaprice, F.; Canci, N.; Candela, A.; Cao, H.; Cariello, M.; Carlini, M.; Catalanotti, S.; Cavalcante, P.; Chepurnov, A.; Cocco, A. G.; Covone, G.; Crippa, L.; D'Incecco, M.; Davini, S.; De Cecco, S.; De Deo, M.; De Vincenzi, M.; Derbin, A.; Devoto, A.; Di Eusanio, F.; Di Pietro, G.; Edkins, E.; Empl, A.; Fan, A.; Fiorillo, G.; Fomenko, K.; Forster, G.; Franco, D.; Gabriele, F.; Galbiati, C.; Giganti, C.; M. Goretti, A.; Granato, F.; Grandi, L.; Gromov, M.; Guan, M.; Guardincerri, Y.; R. Hackett, B.; Herner, K.; V. Hungerford, E.; Ianni, Al.; Ianni, An.; James, I.; Jollet, C.; Keeter, K.; L. Kendziora, C.; Kobychev, V.; Koh, G.; Korablev, D.; Korga, G.; Kubankin, A.; Lissia, M.; Li, X.; Lombardi, P.; Luitz, S.; N. Machulin, I.; Mandarano, A.; Maricic, J.; Marini, L.; M. Mari, S.; J. Martoff, C.; Ma, Y.; Meregaglia, A.; D. Meyers, P.; Miletic, T.; Milincic, R.; Montanari, D.; Monte, A.; Montuschi, M.; Monzani, M.; Mosteiro, P.; J. Mount, B.; N. Muratova, V.; Musico, P.; Napolitano, J.; Nelson, A.; Odrowski, S.; Orsini, M.; Ortica, F.; Pagani, L.; Pallavicini, M.; Pantic, E.; Parmeggiano, S.; Pelczar, K.; Pelliccia, N.; Perasso, S.; Pocar, A.; Pordes, S.; A. Pugachev, D.; Qian, H.; Randle, K.; Ranucci, G.; Razeto, A.; Reinhold, B.; L. Renshaw, A.; Romani, A.; Rossi, B.; Rossi, N.; Rountree, D.; Sablone, D.; Saggese, P.; Saldanha, R.; Sands, W.; Sangiorgio, S.; Savarese, C.; Segreto, E.; A. Semenov, D.; Shields, E.; N. Singh, P.; D. Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Stanford, C.; Suvorov, Y.; Tartaglia, R.; Tatarowicz, J.; Testera, G.; Tonazzo, A.; Trinchese, P.; V. Unzhakov, E.; Vishneva, A.; Vogelaar, B.; Wada, M.; Walker, S.; Wang, H.; Wang, Y.; W. Watson, A.; Westerdale, S.; Wilhelmi, J.; M. Wojcik, M.; Xiang, X.; Xu, J.; Yang, C.; Yoo, J.; Zavatarelli, S.; Zec, A.; Zhong, W.; Zhu, C.; Zuzel, G.

    2017-07-01

    DarkSide (DS) at Gran Sasso underground laboratory is a direct Dark Matter search program based on Time Projection Chambers (TPC) with liquid Argon from underground sources. The DarkSide-50 (DS-50) TPC, with 150kg of Argon is installed inside active neutron and muon detectors. DS-50 has been taking data since November 2013 with Atmospheric Argon (AAr) and since April 2015 with Underground Argon (UAr), depleted in radioactive ^{39} Ar by a factor {˜}1400 . The exposure of 1422kg d of AAr has demonstrated that the operation of DS-50 for three years in a background free condition is a solid reality, thanks to the superb performance of the Pulse Shape Analysis. The first release of results from an exposure of 2616kg d of UAr has shown no candidate Dark Matter events. We have set the best limit for Spin-Independent elastic nuclear scattering of WIMPs obtained by Argon-based detectors, corresponding to a cross-section of 2 10^{-44}{ cm2} at a WIMP mass of 100GeV. We present the detector design and performance, the results from the AAr run and the first results from the UAr run and we briefly introduce the future of the DarkSide program.

  13. Age estimation based on aspartic acid racemization in human sclera.

    PubMed

    Klumb, Karolin; Matzenauer, Christian; Reckert, Alexandra; Lehmann, Klaus; Ritz-Timme, Stefanie

    2016-01-01

    Age estimation based on racemization of aspartic acid residues (AAR) in permanent proteins has been established in forensic medicine for years. While dentine is the tissue of choice for this molecular method of age estimation, teeth are not always available which leads to the need to identify other suitable tissues. We examined the suitability of total tissue samples of human sclera for the estimation of age at death. Sixty-five samples of scleral tissue were analyzed. The samples were hydrolyzed and after derivatization, the extent of aspartic acid racemization was determined by gas chromatography. The degree of AAR increased with age. In samples from younger individuals, the correlation of age and D-aspartic acid content was closer than in samples from older individuals. The age-dependent racemization in total tissue samples proves that permanent or at least long-living proteins are present in scleral tissue. The correlation of AAR in human sclera and age at death is close enough to serve as basis for age estimation. However, the precision of age estimation by this method is lower than that of age estimation based on the analysis of dentine which is due to molecular inhomogeneities of total tissue samples of sclera. Nevertheless, the approach may serve as a valuable alternative or addition in exceptional cases.

  14. Summary of Rocketdyne Engine A5 Rocket Based Combined Cycle Testing

    NASA Technical Reports Server (NTRS)

    Ketchum. A.; Emanuel, Mark; Cramer, John

    1998-01-01

    Rocketdyne Propulsion and Power (RPP) has completed a highly successful experimental test program of an advanced rocket based combined cycle (RBCC) propulsion system. The test program was conducted as part of the Advanced Reusable Technology program directed by NASA-MSFC to demonstrate technologies for low-cost access to space. Testing was conducted in the new GASL Flight Acceleration Simulation Test (FAST) facility at sea level (Mach 0), Mach 3.0 - 4.0, and vacuum flight conditions. Significant achievements obtained during the test program include 1) demonstration of engine operation in air-augmented rocket mode (AAR), ramjet mode and rocket mode and 2) smooth transition from AAR to ramjet mode operation. Testing in the fourth mode (scramjet) is scheduled for November 1998.

  15. A 9,000-year-old caribou hunting structure beneath Lake Huron.

    PubMed

    O'Shea, John M; Lemke, Ashley K; Sonnenburg, Elizabeth P; Reynolds, Robert G; Abbott, Brian D

    2014-05-13

    Some of the most pivotal questions in human history necessitate the investigation of archaeological sites that are now under water. Nine thousand years ago, the Alpena-Amberley Ridge (AAR) beneath modern Lake Huron was a dry land corridor that connected northeast Michigan to southern Ontario. The newly discovered Drop 45 Drive Lane is the most complex hunting structure found to date beneath the Great Lakes. The site and its associated artifacts provide unprecedented insight into the social and seasonal organization of prehistoric caribou hunting. When combined with environmental and simulation studies, it is suggested that distinctly different seasonal strategies were used by early hunters on the AAR, with autumn hunting being carried out by small groups, and spring hunts being conducted by larger groups of cooperating hunters.

  16. Oral cancer statistics in India on the basis of first report of 29 population-based cancer registries

    PubMed Central

    Sharma, Swati; Satyanarayana, L; Asthana, Smitha; Shivalingesh, KK; Goutham, Bala Subramanya; Ramachandra, Sujatha

    2018-01-01

    Objectives: To summarize and provide an overview of age-specific oral cancer incidence reported in 29 population-based cancer registry in India. Materials and Methods: Secondary data on age-adjusted rates (AARs) of incidence of oral cancer and other associated sites for all ages (0–75 years) were collected from the report of the National Cancer Registry Programme 2012–2014 in 29 population-based control registries. Results: Among both males and females, mouth cancer had maximum Age adjusted incidence rates (64.8) in the central zone, while oropharynx cancer had minimum AAR (0) in all regions. Conclusion: Oral cancer incidence increases with age with typical pattern of cancer of associated sites of oral cavity seen in the northeast region. PMID:29731552

  17. A homogeneous method to measure aminoacyl-tRNA synthetase aminoacylation activity using scintillation proximity assay technology.

    PubMed

    Macarrón, R; Mensah, L; Cid, C; Carranza, C; Benson, N; Pope, A J; Díez, E

    2000-09-10

    A new method to measure the aminoacylation of tRNA based upon the use of the scintillation proximity assay (SPA) technology has been developed. The assay detects incorporation of radiolabeled amino acids into cognate tRNA, catalyzed by a specific aminoacyl-tRNA synthetase (aaRS). Under acidic conditions, uncoated yttrium silicate SPA beads were found to bind tRNA aggregates, while the radiolabeled amino acid substrate remains in solution, resulting in good signal discrimination of these two species in the absence of any separation steps. The usefulness of this approach was demonstrated by measurement of steady-state kinetic constants and inhibitor binding constants for a range of aaRS enzymes in comparison with data from standard, trichloroacetic acid-precipitation-based assays. In all cases, the data were quantitatively comparable. Although the radioisotopic counting efficiency of the SPA method was less than that of standard liquid scintillation counting, the statistical performance (i.e., signal to background, variability, stability) of the SPA assays was at least equivalent to the separation-based methods. The assay was also shown to work well in miniaturized 384-well microtiter plate formats, resulting in considerable reagent savings. In summary, a new method to characterize aaRS activity is described that is faster and more amenable to high-throughput screening than traditional methods. Copyright 2000 Academic Press.

  18. Thoracic lymph node station recognition on CT images based on automatic anatomy recognition with an optimal parent strategy

    NASA Astrophysics Data System (ADS)

    Xu, Guoping; Udupa, Jayaram K.; Tong, Yubing; Cao, Hanqiang; Odhner, Dewey; Torigian, Drew A.; Wu, Xingyu

    2018-03-01

    Currently, there are many papers that have been published on the detection and segmentation of lymph nodes from medical images. However, it is still a challenging problem owing to low contrast with surrounding soft tissues and the variations of lymph node size and shape on computed tomography (CT) images. This is particularly very difficult on low-dose CT of PET/CT acquisitions. In this study, we utilize our previous automatic anatomy recognition (AAR) framework to recognize the thoracic-lymph node stations defined by the International Association for the Study of Lung Cancer (IASLC) lymph node map. The lymph node stations themselves are viewed as anatomic objects and are localized by using a one-shot method in the AAR framework. Two strategies have been taken in this paper for integration into AAR framework. The first is to combine some lymph node stations into composite lymph node stations according to their geometrical nearness. The other is to find the optimal parent (organ or union of organs) as an anchor for each lymph node station based on the recognition error and thereby find an overall optimal hierarchy to arrange anchor organs and lymph node stations. Based on 28 contrast-enhanced thoracic CT image data sets for model building, 12 independent data sets for testing, our results show that thoracic lymph node stations can be localized within 2-3 voxels compared to the ground truth.

  19. Molecular Evolution of Aminoacyl tRNA Synthetase Proteins in the Early History of Life

    NASA Astrophysics Data System (ADS)

    Fournier, Gregory P.; Andam, Cheryl P.; Alm, Eric J.; Gogarten, J. Peter

    2011-12-01

    Aminoacyl-tRNA synthetases (aaRS) consist of several families of functionally conserved proteins essential for translation and protein synthesis. Like nearly all components of the translation machinery, most aaRS families are universally distributed across cellular life, being inherited from the time of the Last Universal Common Ancestor (LUCA). However, unlike the rest of the translation machinery, aaRS have undergone numerous ancient horizontal gene transfers, with several independent events detected between domains, and some possibly involving lineages diverging before the time of LUCA. These transfers reveal the complexity of molecular evolution at this early time, and the chimeric nature of genomes within cells that gave rise to the major domains. Additionally, given the role of these protein families in defining the amino acids used for protein synthesis, sequence reconstruction of their pre-LUCA ancestors can reveal the evolutionary processes at work in the origin of the genetic code. In particular, sequence reconstructions of the paralog ancestors of isoleucyl- and valyl- RS provide strong empirical evidence that at least for this divergence, the genetic code did not co-evolve with the aaRSs; rather, both amino acids were already part of the genetic code before their cognate aaRSs diverged from their common ancestor. The implications of this observation for the early evolution of RNA-directed protein biosynthesis are discussed.

  20. 49 CFR 1135.1 - Quarterly adjustment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... railroad productivity as prescribed in Railroad Cost Recovery Procedures, 1 I.C.C.2d 207 (1984), and any subsequent amendments thereto. In addition, the AAR shall calculate the productivity-adjusted RCAF as...

  1. A 9,000-year-old caribou hunting structure beneath Lake Huron

    PubMed Central

    O’Shea, John M.; Lemke, Ashley K.; Sonnenburg, Elizabeth P.; Reynolds, Robert G.; Abbott, Brian D.

    2014-01-01

    Some of the most pivotal questions in human history necessitate the investigation of archaeological sites that are now under water. Nine thousand years ago, the Alpena-Amberley Ridge (AAR) beneath modern Lake Huron was a dry land corridor that connected northeast Michigan to southern Ontario. The newly discovered Drop 45 Drive Lane is the most complex hunting structure found to date beneath the Great Lakes. The site and its associated artifacts provide unprecedented insight into the social and seasonal organization of prehistoric caribou hunting. When combined with environmental and simulation studies, it is suggested that distinctly different seasonal strategies were used by early hunters on the AAR, with autumn hunting being carried out by small groups, and spring hunts being conducted by larger groups of cooperating hunters. PMID:24778246

  2. Routine blood tests to predict liver fibrosis in chronic hepatitis C.

    PubMed

    Hsieh, Yung-Yu; Tung, Shui-Yi; Lee, Kamfai; Wu, Cheng-Shyong; Wei, Kuo-Liang; Shen, Chien-Heng; Chang, Te-Sheng; Lin, Yi-Hsiung

    2012-02-28

    To verify the usefulness of FibroQ for predicting fibrosis in patients with chronic hepatitis C, compared with other noninvasive tests. This retrospective cohort study included 237 consecutive patients with chronic hepatitis C who had undergone percutaneous liver biopsy before treatment. FibroQ, aspartate aminotransferase (AST)/alanine aminotransferase ratio (AAR), AST to platelet ratio index, cirrhosis discriminant score, age-platelet index (API), Pohl score, FIB-4 index, and Lok's model were calculated and compared. FibroQ, FIB-4, AAR, API and Lok's model results increased significantly as fibrosis advanced (analysis of variance test: P < 0.001). FibroQ trended to be superior in predicting significant fibrosis score in chronic hepatitis C compared with other noninvasive tests. FibroQ is a simple and useful test for predicting significant fibrosis in patients with chronic hepatitis C.

  3. Survey of Freight Car Roller Bearing Requirements and Failure Modes

    DOT National Transportation Integrated Search

    1973-07-01

    AAR roller bearing requirements and interchange rules are presented and reviewed; also included and reviewed are rules covering adapters and grease for freight car bearings. Bearing fatigue theory, methods of fatigue life calculations, and characteri...

  4. Acoustic detection of rail car roller bearing defects. Phase III, System evaluation test.

    DOT National Transportation Integrated Search

    2003-08-01

    In July 1999, Transportation Technology Center, Inc. (TTCI), a subsidiary of the Association of American Railroads (AAR), conducted a system evaluation test as part of the Federal Railroad Administrations (FRA) Improved Freight Car Roller Bearing ...

  5. Use of Computer Simulation for the Analysis of Railroad Operations in the St. Louis Terminal Area

    DOT National Transportation Integrated Search

    1977-11-01

    This report discusses the computer simulation methodology, its uses and limitations, and its applicability to the analysis of alternative railroad terminal restructuring plans. Included is a detailed discussion of the AAR Simulation System, an overvi...

  6. Private Sector Involvement in Urban Transportation: Case Studies

    DOT National Transportation Integrated Search

    1984-07-01

    This report describes the development of formulas which predict the severity of accidents at public rail-highway crossings. They employ the previously developed DOT accident prediction formula, U.S. DOT-AAR National Rail-Highway Crossing Inventory, a...

  7. Isotopic evidence for a large-scale plume-derived mantle domain between the Indian and Pacific mantles beneath the Southern Ocean.

    NASA Astrophysics Data System (ADS)

    Park, S. H.; Langmuir, C. H.; Scott, S. R.; Sims, K. W. W.; Lin, J.; Kim, S. S.; Blichert-Toft, J.; Choi, H.; Yang, Y. S.; Michael, P. J.

    2017-12-01

    Earth's upper mantle is characterized by Indian- and Pacific-type domains with distinctive isotope characteristics. The boundary between these two mantle regions has been hypothesized to be located at the Australian-Antarctic-Discordance (AAD), where regions west and east of the AAD are Indian- and Pacific-type, respectively. It was further posited that the Pacific mantle feeds into the Indian mantle as the boundary is moving westward. These scenarios have important implications for the dynamics of mantle convection in the area. In the present model, regions east of the AAD are assumed to be entirely Pacific-type mantle, but our recent recovery of basalts from a 2,000-km sampling gap along the Australian-Antarctic Ridge (AAR), located east of the AAD on the Pacific side, challenges this picture. Here we show that the Hf, Nd, Pb, and Sr isotopic compositions of AAR MORB are distinct from those of Pacific and Indian MORB. Rather, the AAR lavas show mixing relationships with volcanoes from the Hikurangi seamounts, the Balleney and Scott Islands, the West Antarctic Rift System, New Zealand, and east Australia. According to tectonic reconstruction models, these volcanoes are related to super-plume activity that caused Gondwana to break up at 90 Ma. These results imply that a large-scale plume-derived mantle domain exists between the Indian and Pacific mantle domains, and that mantle dynamics along the AAD should be reinterpreted in light of interaction with a super-plume.

  8. Importance of single molecular determinants in the fidelity of expanded genetic codes.

    PubMed

    Antonczak, Alicja K; Simova, Zuzana; Yonemoto, Isaac T; Bochtler, Matthias; Piasecka, Anna; Czapinska, Honorata; Brancale, Andrea; Tippmann, Eric M

    2011-01-25

    The site-selective encoding of noncanonical amino acids (NAAs) is a powerful technique for the installation of novel chemical functional groups in proteins. This is often achieved by recoding a stop codon and requires two additional components: an evolved aminoacyl tRNA synthetase (AARS) and a cognate tRNA. Analysis of the most successful AARSs reveals common characteristics. The highest fidelity NAA systems derived from the Methanocaldococcus jannaschii tyrosyl AARS feature specific mutations to two residues reported to interact with the hydroxyl group of the substrate tyrosine. We demonstrate that the restoration of just one of these determinants for amino acid specificity results in the loss of fidelity as the evolved AARSs become noticeably promiscuous. These results offer a partial explanation of a recently retracted strategy for the synthesis of glycoproteins. Similarly, we reinvestigated a tryptophanyl AARS reported to allow the site-selective incorporation of 5-hydroxy tryptophan within mammalian cells. In multiple experiments, the enzyme displayed elements of promiscuity despite its previous characterization as a high fidelity enzyme. Given the many similarities of the TyrRSs and TrpRSs reevaluated here, our findings can be largely combined, and in doing so they reinforce the long-established central dogma regarding the molecular basis by which these enzymes contribute to the fidelity of translation. Thus, our view is that the central claims of fidelity reported in several NAA systems remain unproven and unprecedented.

  9. Importance of single molecular determinants in the fidelity of expanded genetic codes

    PubMed Central

    Antonczak, Alicja K.; Simova, Zuzana; Yonemoto, Isaac T.; Bochtler, Matthias; Piasecka, Anna; Czapińska, Honorata; Brancale, Andrea; Tippmann, Eric M.

    2011-01-01

    The site-selective encoding of noncanonical amino acids (NAAs) is a powerful technique for the installation of novel chemical functional groups in proteins. This is often achieved by recoding a stop codon and requires two additional components: an evolved aminoacyl tRNA synthetase (AARS) and a cognate tRNA. Analysis of the most successful AARSs reveals common characteristics. The highest fidelity NAA systems derived from the Methanocaldococcus jannaschii tyrosyl AARS feature specific mutations to two residues reported to interact with the hydroxyl group of the substrate tyrosine. We demonstrate that the restoration of just one of these determinants for amino acid specificity results in the loss of fidelity as the evolved AARSs become noticeably promiscuous. These results offer a partial explanation of a recently retracted strategy for the synthesis of glycoproteins. Similarly, we reinvestigated a tryptophanyl AARS reported to allow the site-selective incorporation of 5-hydroxy tryptophan within mammalian cells. In multiple experiments, the enzyme displayed elements of promiscuity despite its previous characterization as a high fidelity enzyme. Given the many similarities of the TyrRSs and TrpRSs reevaluated here, our findings can be largely combined, and in doing so they reinforce the long-established central dogma regarding the molecular basis by which these enzymes contribute to the fidelity of translation. Thus, our view is that the central claims of fidelity reported in several NAA systems remain unproven and unprecedented. PMID:21224416

  10. Pharmacologic Effects of Cannabidiol on Acute Reperfused Myocardial Infarction in Rabbits: Evaluated With 3.0T Cardiac Magnetic Resonance Imaging and Histopathology.

    PubMed

    Feng, Yuanbo; Chen, Feng; Yin, Ting; Xia, Qian; Liu, Yewei; Huang, Gang; Zhang, Jian; Oyen, Raymond; Ni, Yicheng

    2015-10-01

    Cannabidiol (CBD) has anti-inflammatory effects. We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform. Reperfused acute myocardial infarction (AMI) was induced in rabbits with a 90-minute coronary artery occlusion followed by 24-hour reperfusion. Before reperfusion, rabbits received 2 intravenous doses of 100 μg/kg CBD (n = 10) or vehicle (control, n = 10). Evans blue was intravenously injected for later detection of the AMI core. Cardiac magnetic resonance imaging was performed to evaluate cardiac morphology and function. After euthanasia, blood troponin I (cTnI) was assessed, and the heart was excised and infused with multifunctional red iodized oil dye. The heart was sliced for digital radiography to quantify the perfusion density rate, area at risk (AAR), and myocardial salvage index, followed by histomorphologic staining. Compared with controls, CBD treatment improved systolic wall thickening (P < 0.05), significantly increased blood flow in the AAR (P < 0.05), significantly decreased microvascular obstruction (P < 0.05), increased the perfusion density rate by 1.7-fold, lowered the AMI core/AAR ratio (P < 0.05), and increased the myocardial salvage index (P < 0.05). These improvements were associated with reductions in serum cTnI, cardiac leukocyte infiltration, and myocellular apoptosis (P < 0.05). Thus, CBD therapy reduced AMI size and facilitated restoration of left ventricular function. We demonstrated that this experimental platform has potential theragnostic utility.

  11. Amino Acid Availability Controls TRB3 Transcription in Liver through the GCN2/eIF2α/ATF4 Pathway

    PubMed Central

    Carraro, Valérie; Maurin, Anne-Catherine; Lambert-Langlais, Sarah; Averous, Julien; Chaveroux, Cédric; Parry, Laurent; Jousse, Céline; Örd, Daima; Örd, Tõnis; Fafournoux, Pierre; Bruhat, Alain

    2010-01-01

    In mammals, plasma amino acid concentrations are markedly affected by dietary or pathological conditions. It has been well established that amino acids are involved in the control of gene expression. Up to now, all the information concerning the molecular mechanisms involved in the regulation of gene transcription by amino acid availability has been obtained in cultured cell lines. The present study aims to investigate the mechanisms involved in transcriptional activation of the TRB3 gene following amino acid limitation in mice liver. The results show that TRB3 is up-regulated in the liver of mice fed a leucine-deficient diet and that this induction is quickly reversible. Using transient transfection and chromatin immunoprecipitation approaches in hepatoma cells, we report the characterization of a functional Amino Acid Response Element (AARE) in the TRB3 promoter and the binding of ATF4, ATF2 and C/EBPβ to this AARE sequence. We also provide evidence that only the binding of ATF4 to the AARE plays a crucial role in the amino acid-regulated transcription of TRB3. In mouse liver, we demonstrate that the GCN2/eIF2α/ATF4 pathway is essential for the induction of the TRB3 gene transcription in response to a leucine-deficient diet. Therefore, this work establishes for the first time that the molecular mechanisms involved in the regulation of gene transcription by amino acid availability are functional in mouse liver. PMID:21203563

  12. Acoustic detection of roller bearing defects. Phase II, Field test.

    DOT National Transportation Integrated Search

    2000-08-01

    The Transportation Technology Center, Inc. (TTCI), a subsidiary of the Association of American Railroads (AAR) Research and Test Department, conducted a series of simulated revenue service tests with a train of eight cars containing wheel sets with s...

  13. The Use of Cognitive Task Analysis and Simulators for After Action Review of Medical Events in Iraq

    DTIC Science & Technology

    2007-03-01

    research attempts to improve medical AAR with a novel combination of Cognitive Task Analysis (CTA) conducted while interviewees moulage simulators...combination of medical Cognitive Task Analysis combined with the moulage of instruments and depictions of the femoral artery will more accurately

  14. 49 CFR 179.3 - Procedure for securing approval.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS... Safety, AAR, for consideration by its Tank Car Committee and other appropriate committees. Approval or... designs, materials and construction, conversion or alteration of tank car tanks under these specifications...

  15. 49 CFR 179.3 - Procedure for securing approval.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS... Safety, AAR, for consideration by its Tank Car Committee and other appropriate committees. Approval or... designs, materials and construction, conversion or alteration of tank car tanks under these specifications...

  16. 49 CFR 179.3 - Procedure for securing approval.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS... Safety, AAR, for consideration by its Tank Car Committee and other appropriate committees. Approval or... designs, materials and construction, conversion or alteration of tank car tanks under these specifications...

  17. 49 CFR 179.3 - Procedure for securing approval.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS... Safety, AAR, for consideration by its Tank Car Committee and other appropriate committees. Approval or... designs, materials and construction, conversion or alteration of tank car tanks under these specifications...

  18. 49 CFR 179.3 - Procedure for securing approval.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Executive Director—Tank Car Safety, AAR, for consideration by its Tank Car Committee and other appropriate... SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS Introduction, Approvals and Reports § 179.3 Procedure for securing approval. (a) Application...

  19. Bus Driver Fatigue and Stress Issues Study. Final Report

    DOT National Transportation Integrated Search

    1984-04-01

    The study has determined the safety effectiveness of various types of motorist warning devices in reducing accidents at rail-highway crossings. The study was based on analysis of data included in the DOT-AAR Rail-Highway Crossing Inventory and the FR...

  20. 49 CFR 229.217 - Fuel tank.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Locomotive Crashworthiness Design Requirements § 229.217 Fuel..., comply with the requirements of AAR S-5506, “Performance Requirements for Diesel Electric Locomotive Fuel...

  1. Equilibrium Line Altitude fluctuations at HualcaHualca volcano (southern Peru).

    NASA Astrophysics Data System (ADS)

    Alcalá, Jesus; Palacios, David; Juan Zamorano, Jose

    2015-04-01

    Interest in Andean glaciers has substantially increased during the last decades, due to its high sensitivity to climate fluctuations. In this sense, Equilibrium Line Altitude (ELA) is a reliable indicator of climate variability that has been frequently used to reconstruct palaeoenvironmental conditions at different temporal and spatial scales. However, the number of sites with ELA reconstructions is still insufficient to determine patterns in tropical climate or estimations of atmospheric cooling since the Last Glacial Maximum. The main purpose of this study is to contribute in resolving tropical climate evolution through ELA calculations on HualcaHualca (15° 43' S; 71° 52' W; 6,025 masl), a large andesitic stratovolcano located in the south-western Peruvian Andes approximately 70 km north-west of Arequipa. We applied Terminus Headwall Altitude Ratio (THAR) with 0.2; 0.4; 0.5; 0.57 ratios, Accumulation Area Ratio (AAR) and Accumulation Area Balance Ratio (AABR) methods in four valleys of HualcaHualca volcano: Huayuray (north side), Pujro Huayjo (southwest side), Mollebaya (east side) and Mucurca (west side). To estimate ELA depression, we calculated the difference between the ELA on 1955 with its position in the Maximum Glacier Extent (MGE), Tardiglacial phases, little Ice Age (LIA) and 2000. Paleotemperature reconstructions derived from vertical temperature gradient 6.5° C / 1 km, based on GODDARD global observation system considered the most appropriate model for arid Andes. During MGE, the ELA was located between 5,005 (AABR) and 5,215 (AAR 0.67) masl. But in 1955, ELA rose to 5,685 (AABR) - 5,775 (AAR 0.67) masl. The ELA depression between those two phases is 560 - 680 m that implies a temperature decrease of 3.5° - 4.4° C. The experimental process based in the use and contrast of different ELA reconstruction techniques applied in this study suggests that THAR (0.57), AAR (0.67) or AABR are the most consistent procedures for HualcaHualca glaciers, while

  2. The Use of Cognitive Task Analysis and Simulators for After Action Review of Medical Events in Iraq

    DTIC Science & Technology

    2006-12-01

    research attempts to improve medical AAR with a novel combination of Cognitive Task Analysis conducted while interviewees moulage simulators (Clark and...hypothesized that our protocol which employed a novel combination of medical Cognitive Task Analysis combined with the moulage of instruments and depictions

  3. 76 FR 34802 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-14

    ... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2005-21613... amending document dated May 3, 2011, the Association of American Railroads (AAR) has petitioned the Federal Railroad Administration (FRA) for a waiver of compliance from certain provisions of the Federal railroad...

  4. Prostate cell membrane chromatography-liquid chromatography-mass spectrometry for screening of active constituents from Uncaria rhynchophylla.

    PubMed

    He, Jianyu; Han, Shengli; Yang, Fangfang; Zhou, Nan; Wang, Sicen

    2013-01-01

    Uncaria rhynchophylla is a traditional Chinese medicinal herb used to treat hypertension and convulsive disorders such as epilepsy. Rat prostate cell membrane chromatography combined with liquid chromatography-mass spectrometry (LC-MS) was used to identify active constituents from U. rhynchophylla extracts. Four compounds (corynoxeine, isorhynchophylline, isocorynoxeine and rhynchophylline) were discovered. Competitive binding assay results indicated that the four compounds were in direct competition at a single common binding site and interacted with α1A adrenergic receptors (α1A-AR) in a manner similar to tamsulosin. Affinity constant values of the four compounds binding with α1A-AR were also measured using rat prostate cell membrane chromatography (CMC). Finally, their pharmacodynamic effects were tested on rat caudal arteries. This CMC combined LC-MS system offers a means of drug discovery by screening natural medicinal herbs for new pharmacologically active molecules targeting specific receptors.

  5. Aminoacyl-tRNA Synthetases, the Genetic Code, and the Evolutionary Process

    PubMed Central

    Woese, Carl R.; Olsen, Gary J.; Ibba, Michael; Söll, Dieter

    2000-01-01

    The aminoacyl-tRNA synthetases (AARSs) and their relationship to the genetic code are examined from the evolutionary perspective. Despite a loose correlation between codon assignments and AARS evolutionary relationships, the code is far too highly structured to have been ordered merely through the evolutionary wanderings of these enzymes. Nevertheless, the AARSs are very informative about the evolutionary process. Examination of the phylogenetic trees for each of the AARSs reveals the following. (i) Their evolutionary relationships mostly conform to established organismal phylogeny: a strong distinction exists between bacterial- and archaeal-type AARSs. (ii) Although the evolutionary profiles of the individual AARSs might be expected to be similar in general respects, they are not. It is argued that these differences in profiles reflect the stages in the evolutionary process when the taxonomic distributions of the individual AARSs became fixed, not the nature of the individual enzymes. (iii) Horizontal transfer of AARS genes between Bacteria and Archaea is asymmetric: transfer of archaeal AARSs to the Bacteria is more prevalent than the reverse, which is seen only for the “gemini group.” (iv) The most far-ranging transfers of AARS genes have tended to occur in the distant evolutionary past, before or during formation of the primary organismal domains. These findings are also used to refine the theory that at the evolutionary stage represented by the root of the universal phylogenetic tree, cells were far more primitive than their modern counterparts and thus exchanged genetic material in far less restricted ways, in effect evolving in a communal sense. PMID:10704480

  6. Galvanising the NHS to Adopt Innovation

    PubMed Central

    Parris, Stuart; Cochrane, Gavin; Marjanovic, Sonja; Ling, Tom; Chataway, Joanna

    2016-01-01

    Abstract The Department of Health and the Wellcome Trust, in co-operation with NHS England, asked RAND Europe to conduct a limited consultation with key stakeholders about the practicality of measures and incentives proposed as part of the NHS Accelerated Access Review (AAR), which aims to assess the pathways for the development, assessment, and adoption of innovative medicines and medical technology. Through a focused engagement exercise with key healthcare stakeholders this project explored the implications of selected interim AAR propositions and feasibility of implementation for key actors, in primary and secondary care as well as commissioners and academia. Specifically, the project investigated the feasibility of implementation of three specific propositions including: a new earmarked fund to encourage AHSNs and other key innovation actors to re-design systems to embrace innovation; mobilising the influence of clinical system leaders to champion change; and encouraging secondary care organisations to take on “innovation champion” roles linked to financial incentives and a new emphasis on accountable care organisations. Data was collected on the feasibility of the three AAR propositions from a workshop with AHSN CEOs and Commercial Directors and interviews with senior NHS staff in three AHSN regions (South West, University College London Partners, and North East, North Cumbria). The study concludes with reflections on the feasibility of each recommendation and identifies factors expected to facilitate or challenge their implementation, as well as considering the wider cross cutting issues that may influence the adoption and diffusion of innovation in the NHS. PMID:28083436

  7. Distinct Correlation Structure Supporting a Rate-Code for Sound Localization in the Owl’s Auditory Forebrain

    PubMed Central

    2017-01-01

    Abstract While a topographic map of auditory space exists in the vertebrate midbrain, it is absent in the forebrain. Yet, both brain regions are implicated in sound localization. The heterogeneous spatial tuning of adjacent sites in the forebrain compared to the midbrain reflects different underlying circuitries, which is expected to affect the correlation structure, i.e., signal (similarity of tuning) and noise (trial-by-trial variability) correlations. Recent studies have drawn attention to the impact of response correlations on the information readout from a neural population. We thus analyzed the correlation structure in midbrain and forebrain regions of the barn owl’s auditory system. Tetrodes were used to record in the midbrain and two forebrain regions, Field L and the downstream auditory arcopallium (AAr), in anesthetized owls. Nearby neurons in the midbrain showed high signal and noise correlations (RNCs), consistent with shared inputs. As previously reported, Field L was arranged in random clusters of similarly tuned neurons. Interestingly, AAr neurons displayed homogeneous monotonic azimuth tuning, while response variability of nearby neurons was significantly less correlated than the midbrain. Using a decoding approach, we demonstrate that low RNC in AAr restricts the potentially detrimental effect it can have on information, assuming a rate code proposed for mammalian sound localization. This study harnesses the power of correlation structure analysis to investigate the coding of auditory space. Our findings demonstrate distinct correlation structures in the auditory midbrain and forebrain, which would be beneficial for a rate-code framework for sound localization in the nontopographic forebrain representation of auditory space. PMID:28674698

  8. 78 FR 34427 - 2012 Tax Information for Use In The Revenue Shortfall Allocation Method

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-07

    ... Information for Use In The Revenue Shortfall Allocation Method AGENCY: Surface Transportation Board, DOT... of American Railroads (AAR), for use in the Revenue Shortfall Allocation Method (RSAM). DATES... revised in Simplified Standards for Rail Rate Cases--Taxes in Revenue Shortfall Allocation Method, EP 646...

  9. Results and analysis of the switchyard impact tests

    DOT National Transportation Integrated Search

    1980-01-01

    This report presents the results and analysis of series 3 through 7 and series 10 of the FRA/RPI/AAR Switchyard Impact Tests. The test results and analysis are used to evaluate the head shield and the shelf-E coupler as protective devices for hazardo...

  10. LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPS) IN RATS

    EPA Science Inventory

    2003 AAR PM Meeting
    Particulate Matter: Atmospheric Sciences,
    Exposure and the Fourth Colloquium on PM and Human Health

    LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPs) IN RATS. JA Dye, LC Walsh, C...

  11. Complementary Roles of Spark Range and Onboard Free-Flight Measurements for Projectile Development

    DTIC Science & Technology

    2009-08-01

    MET data adequate for aerodynamic analysis requires coordinating with local MET personnel for the release of balloons at strategic times and...TACOM ARDEC AMSRD AAR AEM C M CORZO A READDY R LEE J COSME BLDG 94 PICATINNY ARSENAL NJ 07806-5000 1 COMMANDER US

  12. 77 FR 76169 - Quarterly Rail Cost Adjustment Factor

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-26

    ....stb.dot.gov . Copies of the decision may be purchased by contacting the Office of Public Assistance...)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board, DOT. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the AAR's proposed rebasing calculations and...

  13. Personal Epistemology of Urban Elementary School Teachers

    ERIC Educational Resources Information Center

    Pearrow, Melissa; Sanchez, William

    2008-01-01

    Personal epistemology, originating from social construction theory, provides a framework for researchers to understand how individuals view their world. The Attitudes About Reality (AAR) scale is one survey method that qualitatively assesses personal epistemology along the logical positivist and social constructionist continuum; however, the…

  14. 76 FR 7627 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-10

    .... Eighteen (18) separate groups of locomotives were identified for investigation in the waiver approval... groups that must be investigated. In support of this petition, AAR says that this extension will be... electronic air brake equipment. They have also submitted information from WRE supporting combining EPIC...

  15. 49 CFR 179.100-10 - Postweld heat treatment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.100-10 Postweld heat... heat treated as a unit in compliance with the requirements of AAR Specifications for Tank Cars...

  16. 49 CFR 179.100-10 - Postweld heat treatment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.100-10 Postweld heat... heat treated as a unit in compliance with the requirements of AAR Specifications for Tank Cars...

  17. 49 CFR 179.100-10 - Postweld heat treatment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.100-10 Postweld heat... heat treated as a unit in compliance with the requirements of AAR Specifications for Tank Cars...

  18. Use of Informal Networks to Resolve Logistics-related Issues in Humanitarian Assistance Disaster Response

    DTIC Science & Technology

    2011-06-01

    efforts and the situation objectively and were not tempted to cast themselves in a favorable light ( Podsakoff & Organ, 1986). The AARs and CDRs were...Management.13(3), 146-156. doi: 10.1108/ 13673270910962932. Podsakoff , P.M., & Organ, D.W. (1986). Self-Reports in Organizational Research: Problems

  19. Validation of Arabic and English versions of the ARSMA-II Acculturation Rating Scale.

    PubMed

    Jadalla, Ahlam; Lee, Jerry

    2015-02-01

    To translate and adapt the Acculturation Rating Scale of Mexican-Americans II (ARSMA-II) for Arab Americans. A multistage translation process followed by a pilot and a large study. The translated and adapted versions, Acculturation Rating Scale for Arabic Americans-II Arabic and English (ARSAA-IIA, ARSAA-IIE), were validated in a sample of 297 Arab Americans. Factor analyses with principal axis factoring extractions and direct oblimin rotations were used to identify the underlying structure of ARSAA-II. Factor analysis confirmed the underlying structure of ARSAA-II and produced two interpretable factors labeled as 'Attraction to American Culture' (AAmC) and 'Attraction to Arabic Culture' (AArC). The Cronbach's alphas of AAmC and AArC were .89 and .85 respectively. Findings support ARSAA-II A & E to assess acculturation among Arab Americans. The emergent factors of ARSAA-II support the theoretical structure of the original ARSMA-II tool and show high internal consistency.

  20. Direct dating of human fossils.

    PubMed

    Grün, Rainer

    2006-01-01

    The methods that can be used for the direct dating of human remains comprise of radiocarbon, U-series, electron spin resonance (ESR), and amino acid racemization (AAR). This review gives an introduction to these methods in the context of dating human bones and teeth. Recent advances in ultrafiltration techniques have expanded the dating range of radiocarbon. It now seems feasible to reliably date bones up to 55,000 years. New developments in laser ablation mass spectrometry permit the in situ analysis of U-series isotopes, thus providing a rapid and virtually non-destructive dating method back to about 300,000 years. This is of particular importance when used in conjunction with non-destructive ESR analysis. New approaches in AAR analysis may lead to a renaissance of this method. The potential and present limitations of these direct dating techniques are discussed for sites relevant to the reconstruction of modern human evolution, including Florisbad, Border Cave, Tabun, Skhul, Qafzeh, Vindija, Banyoles, and Lake Mungo. (c) 2006 Wiley-Liss, Inc.

  1. 76 FR 40448 - 2010 Tax Information for Use in the Revenue Shortfall Allocation Method

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-08

    ... Information for Use in the Revenue Shortfall Allocation Method AGENCY: Surface Transportation Board. ACTION... Railroads (AAR), for use in the Revenue Shortfall Allocation Method (RSAM). DATES: Comments are due by... Allocation Method, EP 646 (Sub-No. 2) (STB served Nov. 21, 2008). RSAM is intended to measure the average...

  2. 76 FR 35026 - Weather Shield Manufacturing, Inc. Corporate Office, Medford, WI; Notice of Amended Negative...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    ... subject firm's major declining customers regarding their purchases of doors and/or windows in the relevant period. AAR 29-48. The survey revealed that customer imports of articles like or directly competitive... customer list or any list of the customers to whom Labor issued questionnaires.'') The materials to which...

  3. 78 FR 7857 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-04

    ... below have been forwarded to the Office of Management and Budget (OMB) for review and comment. The ICRs... brand identification of the material. (3) Each individual unit of a glazing material that has...) the manufacturer of the material; (iii) the type or brand identification of the material. AAR believes...

  4. 49 CFR 179.300-10 - Postweld heat treatment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Multi-Unit Tank Car Tanks (Classes DOT-106A and 110AW) § 179.300-10 Postweld heat treatment... as a unit in compliance with the requirements of AAR Specifications for Tank Cars, appendix W (IBR...

  5. 49 CFR 179.100-12 - Manway nozzle, cover and protective housing.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120... with the requirements of AAR Specifications for Tank Cars, appendix E, Figure E10 (IBR, see § 171.7 of...

  6. 49 CFR 179.100-12 - Manway nozzle, cover and protective housing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120... with the requirements of AAR Specifications for Tank Cars, appendix E, Figure E10 (IBR, see § 171.7 of...

  7. 49 CFR 179.100-12 - Manway nozzle, cover and protective housing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120... with the requirements of AAR Specifications for Tank Cars, appendix E, Figure E10 (IBR, see § 171.7 of...

  8. 49 CFR 179.300-10 - Postweld heat treatment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Multi-Unit Tank Car Tanks (Classes DOT-106A and 110AW) § 179.300-10 Postweld heat treatment... as a unit in compliance with the requirements of AAR Specifications for Tank Cars, appendix W (IBR...

  9. 49 CFR 179.100-12 - Manway nozzle, cover and protective housing.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120... with the requirements of AAR Specifications for Tank Cars, appendix E, Figure E10 (IBR, see § 171.7 of...

  10. Operational Performance of the U.S. 28th Infantry Division September to December 1944

    DTIC Science & Technology

    1994-06-03

    Kansas. Hereafter referred to as V Corps, G-I AAR. 12. Ibid. 12. Charlie Waldrup, Voices From The Foxholes (Edited by Dorothy Chernitsky , Uniontown, PA...Foxholes. Edited by Dorothy Chernitsky (Uniontown, PA: Published by the Author, 1991), 233-234. 36. MacDonald and Mathews, Three.Battle, 344-345. 37

  11. 49 CFR 171.7 - Reference material.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Equipped Freight Car and Intermodal Equipment, 1988 174.55; 174.63. AAR Specifications for Design... Pamphlet C-8, Standard for Requalification of DOT-3HT Cylinder Design, 1985 180.205; 180.209. CGA Pamphlet C-11, Recommended Practices for Inspection of Compressed Gas Cylinders at Time of Manufacture, 2001...

  12. 49 CFR 171.7 - Reference material.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Car and Intermodal Equipment, 1988 174.55; 174.63. AAR Specifications for Design, Fabrication and... Pamphlet C-8, Standard for Requalification of DOT-3HT Cylinder Design, 1985 180.205; 180.209. CGA Pamphlet C-11, Recommended Practices for Inspection of Compressed Gas Cylinders at Time of Manufacture, 2001...

  13. Compression and Associated Properties of Boron Carbide

    DTIC Science & Technology

    2008-12-01

    of Brookhaven National Laboratory ( BNL ) with the light extracted from the x-ray source in a method previously described (Liu et al., 2002).. A...are sharper and more intense relative to as received material. ACKNOWLEDGMENTS Thanks are due to Dr. Jingzhu Hu and Dr. Zhenxian Liu of BNL

  14. Noninvasive Assessment of Liver Fibrosis Stage Using Ultrasound-Based Shear Wave Velocity Measurements and Serum Algorithms in Patients With Viral Hepatitis B: A Retrospective Cohort Study.

    PubMed

    Liu, Jianxue; Zhao, Junzhi; Zhang, Yaoren; Ji, Yonghao; Lin, Shumei; Dun, Guoliang; Guo, Sujuan

    2017-02-01

    Liver biopsy remains the reference standard for the assessment of liver fibrosis, but this procedure is invasive and can lead to complications. Thus, studies to determine the optimal noninvasive test are warranted. This study compared several noninvasive tests and their combinations for evaluating liver fibrosis stages in patients with chronic hepatitis B. The shear wave velocity (SWV) and laboratory indicators were collected from 174 patients with chronic hepatitis B. Formulas were applied to calculate the serum fibrosis model, including the aspartate aminotransaminase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4) and aspartate aminotransferase-to-alanine aminotransferase ratio (AAR). The diagnostic performance of all noninvasive tests was assessed in comparison with percutaneous liver biopsy, based on a receiver operating characteristic curve analysis. The SWV (area under the receiver operating characteristic curve [AUC], 0.82) and APRI (AUC = 0.77) performed better than the FIB-4 (AUC = 0.62), and the AAR (AUC = 0.47) was not suitable for evaluating substantial liver fibrosis (stage ≥F2). The SWV (AUC = 0.96) was the best indicator, being superior to the APRI (AUC = 0.75) and FIB-4 (AUC = 0.74), and the AAR (AUC = 0.45) was not suitable for assessing cirrhosis (F4). Combining the SWV and APRI, the AUC improved to 0.85 for substantial liver fibrosis, and the sensitivity increased to 100% for cirrhosis. The SWV, APRI, and FIB-4 were valid tests for evaluating substantial liver fibrosis and cirrhosis. The combination of these tests with several noninvasive indicators is expected to enhance the assessment of liver fibrosis stages. © 2016 by the American Institute of Ultrasound in Medicine.

  15. Command Center Training Tool (C2T2)

    NASA Technical Reports Server (NTRS)

    Jones, Phillip; Drucker, Nich; Mathews, Reejo; Stanton, Laura; Merkle, Ed

    2012-01-01

    This abstract presents the training approach taken to create a management-centered, experiential learning solution for the Virginia Port Authority's Port Command Center. The resultant tool, called the Command Center Training Tool (C2T2), follows a holistic approach integrated across the training management cycle and within a single environment. The approach allows a single training manager to progress from training design through execution and AAR. The approach starts with modeling the training organization, identifying the organizational elements and their individual and collective performance requirements, including organizational-specific performance scoring ontologies. Next, the developer specifies conditions, the problems, and constructs that compose exercises and drive experiential learning. These conditions are defined by incidents, which denote a single, multi-media datum, and scenarios, which are stories told by incidents. To these layered, modular components, previously developed meta-data is attached, including associated performance requirements. The components are then stored in a searchable library An event developer can create a training event by searching the library based on metadata and then selecting and loading the resultant modular pieces. This loading process brings into the training event all the previously associated task and teamwork material as well as AAR preparation materials. The approach includes tools within an integrated management environment that places these materials at the fingertips of the event facilitator such that, in real time, the facilitator can track training audience performance and resultantly modify the training event. The approach also supports the concentrated knowledge management requirements for rapid preparation of an extensive AAR. This approach supports the integrated training cycle and allows a management-based perspective and advanced tools, through which a complex, thorough training event can be developed.

  16. Overview of overseas humanitarian, disaster, and civic aid programs.

    PubMed

    Drifmeyer, Jeff; Llewellyn, Craig

    2003-12-01

    The U.S. Department of Defense (DoD) conducts humanitarian assistance missions under the Overseas Humanitarian Disaster and Civic Aid program for the statutory purposes of training military personnel, serving the political interests of the host nation and United States, and providing humanitarian relief to foreign civilians. These purposes are undertaken via the humanitarian assistance (HA), humanitarian and civic assistance, and excess property donation programs. DoD conducts over 200 such projects annually at a direct cost of approximately 27 million dollars in fiscal year 2001. Although varying by year and command, as many as one-half of these projects involve aspects of health care. These range from short-term patient care to donation of medical supplies and equipment excess to the needs of the DoD. Despite the considerable resources invested and importance of international actions, there is presently no formal evaluation system for these HA projects. Current administrative staffing of these programs by military personnel is often by individuals with many other duties and responsibilities. As a result, humanitarian projects are often inadequately coordinated with nongovernmental organizations, private volunteer organizations, or host-nation officials. Nonmedical military personnel sometimes plan health-related projects with little or no coordination with medical experts, military or civilian. After action reports (AARs) on these humanitarian projects are often subjective, lack quantitative details, and are devoid of measures of effectiveness. AARs are sometimes inconsistently completed, and there is no central repository of information for analysis of lessons learned. (The approximate 100 AARs used in the conduct of these studies are available for official use in the Learning Resources Center, Uniformed Services University of Health Sciences.) Feedback from past humanitarian projects is rare and with few exceptions; DoD-centric projects of a similar design are

  17. Quantification of both the area-at-risk and acute myocardial infarct size in ST-segment elevation myocardial infarction using T1-mapping.

    PubMed

    Bulluck, Heerajnarain; Hammond-Haley, Matthew; Fontana, Marianna; Knight, Daniel S; Sirker, Alex; Herrey, Anna S; Manisty, Charlotte; Kellman, Peter; Moon, James C; Hausenloy, Derek J

    2017-08-01

    A comprehensive cardiovascular magnetic resonance (CMR) in reperfused ST-segment myocardial infarction (STEMI) patients can be challenging to perform and can be time-consuming. We aimed to investigate whether native T1-mapping can accurately delineate the edema-based area-at-risk (AAR) and post-contrast T1-mapping and synthetic late gadolinium (LGE) images can quantify MI size at 1.5 T. Conventional LGE imaging and T2-mapping could then be omitted, thereby shortening the scan duration. Twenty-eight STEMI patients underwent a CMR scan at 1.5 T, 3 ± 1 days following primary percutaneous coronary intervention. The AAR was quantified using both native T1 and T2-mapping. MI size was quantified using conventional LGE, post-contrast T1-mapping and synthetic magnitude-reconstructed inversion recovery (MagIR) LGE and synthetic phase-sensitive inversion recovery (PSIR) LGE, derived from the post-contrast T1 maps. Native T1-mapping performed as well as T2-mapping in delineating the AAR (41.6 ± 11.9% of the left ventricle [% LV] versus 41.7 ± 12.2% LV, P = 0.72; R 2 0.97; ICC 0.986 (0.969-0.993); bias -0.1 ± 4.2% LV). There were excellent correlation and inter-method agreement with no bias, between MI size by conventional LGE, synthetic MagIR LGE (bias 0.2 ± 2.2%LV, P = 0.35), synthetic PSIR LGE (bias 0.4 ± 2.2% LV, P = 0.060) and post-contrast T1-mapping (bias 0.3 ± 1.8% LV, P = 0.10). The mean scan duration was 58 ± 4 min. Not performing T2 mapping (6 ± 1 min) and conventional LGE (10 ± 1 min) would shorten the CMR study by 15-20 min. T1-mapping can accurately quantify both the edema-based AAR (using native T1 maps) and acute MI size (using post-contrast T1 maps) in STEMI patients without major cardiovascular risk factors. This approach would shorten the duration of a comprehensive CMR study without significantly compromising on data acquisition and would obviate the need to perform T2 maps and LGE imaging.

  18. Effects of Synephrine and B-Phenethylamine on Human a-Adrenoceptor Subtypes

    USDA-ARS?s Scientific Manuscript database

    Synephrine and B-phenethylamine are structurally related to ephedrine. In this study, the effects of synephrine and B-phenethylamine are investigated on a-adrenoceptor (a-AR) subtypes expressed in human embroyonic kidney (HEK293) or Chinese hamster ovary (CHO) cells, and compared to that of 1R,2S-no...

  19. 49 CFR 179.200-13 - Manway ring or flange, pressure relief device flange, bottom outlet nozzle flange, bottom washout...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179..., figure 10, of the AAR Specifications for Tank Cars (IBR, see § 171.7 of this subchapter). (b) The opening...

  20. 49 CFR 179.200-13 - Manway ring or flange, pressure relief device flange, bottom outlet nozzle flange, bottom washout...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179..., figure 10, of the AAR Specifications for Tank Cars (IBR, see § 171.7 of this subchapter). (b) The opening...

  1. 49 CFR 179.200-13 - Manway ring or flange, pressure relief device flange, bottom outlet nozzle flange, bottom washout...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179..., figure 10, of the AAR Specifications for Tank Cars (IBR, see § 171.7 of this subchapter). (b) The opening...

  2. 49 CFR 179.200-11 - Postweld heat treatment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179.200-11 Postweld heat treatment... with the requirements of AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7 of this...

  3. 49 CFR 179.200-13 - Manway ring or flange, pressure relief device flange, bottom outlet nozzle flange, bottom washout...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179..., figure 10, of the AAR Specifications for Tank Cars (IBR, see § 171.7 of this subchapter). (b) The opening...

  4. 49 CFR 179.220-11 - Postweld heat treatment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179.220-11 Postweld heat treatment... attached must comply with AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7 of this subchapter...

  5. 49 CFR 179.200-11 - Postweld heat treatment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179.200-11 Postweld heat treatment... with the requirements of AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7 of this...

  6. 49 CFR 179.200-11 - Postweld heat treatment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179.200-11 Postweld heat treatment... with the requirements of AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7 of this...

  7. 49 CFR 179.201-6 - Manways and manway closures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179.201-6... in AAR Specifications for Tank Cars, appendix M, M3.03 (IBR, see § 171.7 of this subchapter). [Amdt...

  8. 49 CFR 179.4 - Changes in specifications for tank cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Changes in specifications for tank cars. 179.4... TANK CARS Introduction, Approvals and Reports § 179.4 Changes in specifications for tank cars. (a...—Tank Car Safety, AAR, for consideration by its Tank Car Committee. An application for construction of...

  9. 78 FR 51078 - Reporting Requirements for Positive Train Control Expenses and Investments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-20

    ... useful in making regulatory policy and business decisions. The new rule will require a PTC Supplement \\5... interested parties with data useful in making regulatory policy and business decisions. PTC grants. AAR and... useful in regulatory decision making.\\45\\ They also argue that the burden will be on the carriers to...

  10. 49 CFR 179.102-4 - Vinyl fluoride, stabilized.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Include impact specimens of weld metal and heat affected zone prepared and tested in accordance with AAR.... (b) Insulation must be of approved material. (c) Excess flow valves must be installed under all... capacity stencil, MINIMUM OPERATING TEMPERATURE _ °F. (i) The tank car and insulation must be designed to...

  11. AAR in concrete of Asejire spillway (OYO state - Nigeria)

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

    Lamaudiere, J.P.; Spaeti, F.

    1995-12-31

    The Asejire dam at Ibadan, Nigeria was constructed in the late sixties for the purpose of providing water for the city of Ibadan (presently about 4,5 million inhabitants). It is located on the Oshun river approximately fifteen miles from the city. In 1982 cracks were observed on the wing walls and although these continued to develop, no attempt was made at that time to investigate their causes and no repair was carried out. In 1989 the SGI ENGINEERING Group of Geneva, Switzerland was appointed as the consultant for the complete refurbishment of the Asejire water scheme. The consortium Degremont-Poat-Clemessy wasmore » awarded the contract for the project. The African Development Bank and the Nigerian Government have provided the loan to finance the project.« less

  12. 49 CFR 232.307 - Modification of the single car air brake test procedures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Modification of the single car air brake test... Requirements § 232.307 Modification of the single car air brake test procedures. (a) Request. The AAR or other authorized representative of the railroad industry may seek modification of the single car air brake test...

  13. 49 CFR 232.307 - Modification of the single car air brake test procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Modification of the single car air brake test... Requirements § 232.307 Modification of the single car air brake test procedures. (a) Request. The AAR or other authorized representative of the railroad industry may seek modification of the single car air brake test...

  14. 49 CFR 179.102-4 - Vinyl fluoride, stabilized.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... weld metal and heat affected zone prepared and tested in accordance with AAR Specifications for Tank...) Insulation must be of approved material. (c) Excess flow valves must be installed under all liquid and vapor... OPERATING TEMPERATURE _ °F. (i) The tank car and insulation must be designed to prevent the vapor pressure...

  15. 49 CFR 179.102-4 - Vinyl fluoride, stabilized.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... weld metal and heat affected zone prepared and tested in accordance with AAR Specifications for Tank...) Insulation must be of approved material. (c) Excess flow valves must be installed under all liquid and vapor... OPERATING TEMPERATURE _ °F. (i) The tank car and insulation must be designed to prevent the vapor pressure...

  16. 49 CFR 179.102-4 - Vinyl fluoride, stabilized.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... weld metal and heat affected zone prepared and tested in accordance with AAR Specifications for Tank...) Insulation must be of approved material. (c) Excess flow valves must be installed under all liquid and vapor... OPERATING TEMPERATURE _ °F. (i) The tank car and insulation must be designed to prevent the vapor pressure...

  17. 49 CFR 179.102-4 - Vinyl fluoride, stabilized.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... weld metal and heat affected zone prepared and tested in accordance with AAR Specifications for Tank...) Insulation must be of approved material. (c) Excess flow valves must be installed under all liquid and vapor... OPERATING TEMPERATURE _ °F. (i) The tank car and insulation must be designed to prevent the vapor pressure...

  18. 77 FR 42704 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-20

    ... Vision Sensors, 12 AN/APG-78 Fire Control Radars (FCR) with Radar Electronics Unit (LONGBOW component... Target Acquisition and Designation Sight, 27 AN/AAR-11 Modernized Pilot Night Vision Sensors, 12 AN/APG... enhance the protection of key oil and gas infrastructure and platforms which are vital to U.S. and western...

  19. A New Key to Scholarly Collaboration?

    ERIC Educational Resources Information Center

    Fitzmier, Jack

    2012-01-01

    The American Academy of Religion, in concert with the Sakai Foundation, has envisioned a scholarly use of the new Sakai Open Academic Environment open-source software. Currently working under the title "Biosphere," the program would put a rich collection of collaborative tools in the hands of AAR members, their colleagues in related scholarly…

  20. 49 CFR 173.247 - Bulk packaging for certain elevated temperature materials.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... motor vehicles; and non-DOT specification cargo tank motor vehicles equivalent in structural design and...; metal IBCs and non-specification portable tanks equivalent in structural design and accident damage...; Class DOT 106, 110 multi-unit tank car tanks; AAR Class 203W, 206W, 211W tank car tanks; and non-DOT...

  1. 49 CFR 173.247 - Bulk packaging for certain elevated temperature materials.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... motor vehicles; and non-DOT specification cargo tank motor vehicles equivalent in structural design and...; metal IBCs and non-specification portable tanks equivalent in structural design and accident damage...; Class DOT 106, 110 multi-unit tank car tanks; AAR Class 203W, 206W, 211W tank car tanks; and non-DOT...

  2. 49 CFR 173.247 - Bulk packaging for certain elevated temperature materials.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... motor vehicles; and non-DOT specification cargo tank motor vehicles equivalent in structural design and...; metal IBCs and non-specification portable tanks equivalent in structural design and accident damage...; Class DOT 106, 110 multi-unit tank car tanks; AAR Class 203W, 206W, 211W tank car tanks; and non-DOT...

  3. 49 CFR 173.247 - Bulk packaging for certain elevated temperature materials.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... motor vehicles; and non-DOT specification cargo tank motor vehicles equivalent in structural design and...; metal IBCs and non-specification portable tanks equivalent in structural design and accident damage...; Class DOT 106, 110 multi-unit tank car tanks; AAR Class 203W, 206W, 211W tank car tanks; and non-DOT...

  4. 49 CFR 232.307 - Modification of the single car air brake test procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Requirements § 232.307 Modification of the single car air brake test procedures. (a) Request. The AAR or other authorized representative of the railroad industry may seek modification of the single car air brake test... 49 Transportation 4 2010-10-01 2010-10-01 false Modification of the single car air brake test...

  5. 49 CFR 232.307 - Modification of the single car air brake test procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Requirements § 232.307 Modification of the single car air brake test procedures. (a) Request. The AAR or other authorized representative of the railroad industry may seek modification of the single car air brake test... 49 Transportation 4 2011-10-01 2011-10-01 false Modification of the single car air brake test...

  6. 49 CFR 232.307 - Modification of the single car air brake test procedures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Requirements § 232.307 Modification of the single car air brake test procedures. (a) Request. The AAR or other authorized representative of the railroad industry may seek modification of the single car air brake test... 49 Transportation 4 2012-10-01 2012-10-01 false Modification of the single car air brake test...

  7. 49 CFR 179.220-6 - Thickness of plates.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... heads; P = Minimum required bursting pressure in psig; S = Minimum tensile strength of plate material in p.s.i. as prescribed in AAR Specifications for Tank Cars, appendix M, Table M1; t = Minimum... seamless heads; L = Main inside radius to which head is dished, measured on concave side in inches; P...

  8. 78 FR 47824 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-06

    ... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2013-0077] Petition for Waiver of Compliance In accordance with Part 211 of Title 49 Code of Federal Regulations (CFR), this document provides the public notice that by a document dated July 16, 2013, the Association of American Railroads (AAR) has petitioned the...

  9. 78 FR 46680 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-01

    ...] Petition for Waiver of Compliance In accordance with Part 211 of Title 49 Code of Federal Regulations (CFR... Administration (FRA) for a waiver of compliance from certain provisions of the Federal railroad safety.... Specifically, AAR seeks a waiver of compliance from Part 232, Appendix B, Part 232 Prior to May 31, 2001 as...

  10. Buyid Silk and the Tale of Bibi Shahrbanu: Identification of Biomarkers of Artificial Aging (Forgery) of Silk.

    PubMed

    Moini, Mehdi; Rollman, Christopher M

    2017-10-03

    Buyid silk forgery is one of the most famous silk forgeries in the world. In 1924-1925, excavation of the Bibi Shahrbanu site in Iran unearthed several silk textiles. The silks were thought to be of the Buyid period (934-1062 BCE) of the Persian Empire and have since been known as the "Buyid silks". In the 1930s, more silk appeared and was reported as being from the Buyid period as well. Controversy over the authenticity of these silks escalated after the purchase of the silks by museums throughout the world. Extensive investigations of several of these silks have been conducted over the years with respect to iconography, weaving patterns, dyes/mordant, style, and even radiocarbon dating. It was found that most of the silks are not from Buyid period. To test the authenticity of these silk fabrics, the recently developed silk dating technique using amino acid racemization (AAR) in conjunction with capillary electrophoresis mass spectrometry was applied to 13 Buyid silk specimens from the Textile Museum collections. Among these silk specimens, the AAR ratios of only one specimen were consistent with authentic silk fabrics collected from various museums. In addition, the aspartic acid racemization ratio of this specimen was also consistent with its 14 C dating. The other "Buyid silks" showed excessive levels of amino acid racemization not only for aspartic acid, but also for phenylalanine and tyrosine, inconsistent with racemization rates of these amino acids in authentic historical silk fabrics. Treatment of modern silk with a base at different pH and temperature reproduced the AAR pattern of the Buyid silks, implying that chemical treatment with a base at relatively high temperatures was perhaps the method used to artificially age these fabrics. The results imply that the racemization ratios of aspartic acid, phenylalanine, and tyrosine can be used as biomarkers for identification of naturally versus artificially aged silk.

  11. Alkane Biosynthesis Genes in Cyanobacteria and Their Transcriptional Organization

    PubMed Central

    Klähn, Stephan; Baumgartner, Desirée; Pfreundt, Ulrike; Voigt, Karsten; Schön, Verena; Steglich, Claudia; Hess, Wolfgang R.

    2014-01-01

    In cyanobacteria, alkanes are synthesized from a fatty acyl-ACP by two enzymes, acyl–acyl carrier protein reductase and aldehyde deformylating oxygenase. Despite the great interest in the exploitation for biofuel production, nothing is known about the transcriptional organization of their genes or the physiological function of alkane synthesis. The comparison of 115 microarray datasets indicates the relatively constitutive expression of aar and ado genes. The analysis of 181 available genomes showed that in 90% of the genomes both genes are present, likely indicating their physiological relevance. In 61% of them they cluster together with genes encoding acetyl-CoA carboxyl transferase and a short-chain dehydrogenase, strengthening the link to fatty acid metabolism and in 76% of the genomes they are located in tandem, suggesting constraints on the gene arrangement. However, contrary to the expectations for an operon, we found in Synechocystis sp. PCC 6803 specific promoters for the two genes, sll0208 (ado) and sll0209 (aar), which give rise to monocistronic transcripts. Moreover, the upstream located ado gene is driven by a proximal as well as a second, distal, promoter, from which a third transcript, the ~160 nt sRNA SyR9 is transcribed. Thus, the transcriptional organization of the alkane biosynthesis genes in Synechocystis sp. PCC 6803 is of substantial complexity. We verified all three promoters to function independently from each other and show a similar promoter arrangement also in the more distant Nodularia spumigena, Trichodesmium erythraeum, Anabaena sp. PCC 7120, Prochlorococcus MIT9313, and MED4. The presence of separate regulatory elements and the dominance of monocistronic mRNAs suggest the possible autonomous regulation of ado and aar. The complex transcriptional organization of the alkane synthesis gene cluster has possible metabolic implications and should be considered when manipulating the expression of these genes in cyanobacteria. PMID

  12. Management of benign prostatic hyperplasia with silodosin

    PubMed Central

    Yamanishi, Tomonori; Mizuno, Tomoya; Kamai, Takao; Yoshida, Ken-Ichiro; Sakakibara, Ryuji; Uchiyama, Tomoyuki

    2009-01-01

    It has been reported that blockade of α1A-adrenoceptor (AR) relieves bladder outlet obstruction, while blockade of α1D-AR is believed to alleviate storage symptoms due to detrusor overactivity. Silodosin, (−)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy) phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7- carboxamide, is a new α1A-AR selective antagonist. Silodosin is highly selective for the α1A-AR subtype, showing an affinity for the α1A-AR that is 583- and 55.5-fold higher than its affinity for the α1B-and α1D-ARs, respectively. In randomized, double-blind, placebo-controlled phase III studies performed in Japan and the United States, silodosin has been shown to be effective for both storage and voiding symptoms associated with benign prostatic hyperplasia. Early effects of silodosin (after 2–6 hours or day 1) on lower urinary tract symptoms have also been reported. In urodynamic studies, detrusor overactivity disappeared in 40% and improved in 35% of patients after administration. In pressure flow studies, the grade of obstruction on the International Continence Society nomogram showed improvement in 56% of patients. The rate of adverse events in the silodosin, tamsulosin and placebo groups was 88.6%, 82.3%, and 71.6%, respectively. The most common adverse event was (mostly mild) abnormal ejaculation (28.1%). However, few patients (2.8%) discontinued silodosin because of abnormal ejaculation. Orthostatic hypotension showed a similar incidence in the silodosin (2.6%) and placebo (1.5%) groups. In conclusion, silodosin improves detrusor overactivity and obstruction and thus may be effective for both storage and voiding symptoms in patients with benign prostatic hyperplasia. PMID:24198606

  13. Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model

    PubMed Central

    2010-01-01

    Background Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods In anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability. PMID:20875134

  14. [Comparison of various noninvasive serum markers of liver fibrosis in chronic viral liver disease].

    PubMed

    Kim, Sun Min; Sohn, Joo Hyun; Kim, Tae Yeob; Roh, Young Wook; Eun, Chang Soo; Jeon, Yong Cheol; Han, Dong Soo; Oh, Young Ha

    2009-12-01

    The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (> or =F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (> or =F3). All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis.

  15. Cancer in American Indian and Alaska Native young adults (ages 20-44 years): US, 1999-2004.

    PubMed

    Weir, Hannah K; Jim, Melissa A; Marrett, Loraine D; Fairley, Temeika

    2008-09-01

    An examination of cancer incidence patterns in American Indians and Alaska Native (AI/AN) young adults may provide insight into their present and future cancer burden. To reduce racial misclassification, incidence data were linked with the Indian Health Service (IHS) patient services database. Age-adjusted cancer incidence rates per 100,000 (AAR) and corresponding rate ratios (RR) for young adults (ages 20-44 years) were compared across IHS regions and for selected cancers within Contract Health Service Delivery Area counties by race (AI/AN vs non-Hispanic whites [NHW]) and sex. The all-sites cancer incidence rate was lower for AI/ANs (AAR of 83.8) than for NHWs (AAR of 111.2) (RR of 0.75) but varied by IHS regions. Among the leading cancers in AI/AN females the risk was elevated for stomach (RR of 3.22), colorectal (RR of 1.30), uterine (RR of 1.61), and kidney (RR of 1.39) cancers and was lower for breast (RR of 0.70) and thyroid (RR of 0.71) cancers. Among AI/AN young adult males the risk was elevated for stomach (RR of 2.62), liver (RR of 1.89), and kidney (RR of 1.59) cancers and lower for testicular germ cell cancer (RR of 0.64) and lymphoma (RR of 0.60). The risk for these and other cancers varied across IHS regions. Many of the cancer patterns that characterize the AI/AN population overall are apparent among young adults. Compared with NHW young adults, the overall cancer burden among AI/AN young adults was lower but varied for selected cancers and across IHS regions. Cancer control and research strategies are needed to address the unique genetic, social, cultural, and lifestyle aspects of AI/AN young adults.

  16. Suboptimal performance of simple noninvasive tests for advanced fibrosis in Chinese patients with nonalcoholic fatty liver disease.

    PubMed

    Xun, Yun Hao; Fan, Jian Gao; Zang, Guo Qing; Liu, Hong; Jiang, Yan Ming; Xiang, Jing; Huang, Qian; Shi, Jun Ping

    2012-11-01

    To evaluate the diagnostic accuracy of some noninvasive fibrosis models in Chinese patients with nonalcoholic fatty liver disease (NAFLD). Consecutive biopsy-proven NAFLD patients were recruited from a single center from January 2005 to December 2010. Advanced fibrosis (stage 3 and 4) was defined using Kleiner criteria. The area under the receiver operating characteristic curve (AUROC) was used to compare the diagnostic accuracy of the NAFLD fibrosis score (NFS), FIB-4 index, aspartate transaminase (AST)/platelet ratio index (APRI), AST/alanine transaminase (ALT) ratio (AAR) and body mass index (BMI)-AAR-Diabetes (BARD) score. Of the patients with NAFLD, 79.6% were males with a mean age of 37.1 years, mean BMI of 26.1 kg/m(2) and 41.4% of them had nonalcoholic steatohepatitis, and 24 (15.8%) had advanced fibrosis. The AUROC of the FIB-4 index, APRI, AAR, NFS and BARD score for advanced fibrosis were 0.756, 0.742, 0.670, 0.653 and 0.642 (P < 0.05 for all), respectively. A concordant negative predictive value of approximately 90% was indicated whereas the positive predictive values were modest for all tests, and only the FIB-4 index yielded a higher positive likelihood ratio of 7.65. Using these cut-off values of tests for excluding advanced fibrosis could reduce the use of liver biopsy in 56.6-74.3% of the patients, with a minor false negative rate of 5.3-9.9%. Although slightly less accurate than liver biopsy, simple noninvasive tests can reliably exclude advanced fibrosis in Chinese NAFLD patients in our center. FIB-4 index performs better than the other tests under examination. © 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  17. Genetic variations in the α(2A)-adrenoreceptor are associated with blood pressure response to the agonist dexmedetomidine.

    PubMed

    Kurnik, Daniel; Muszkat, Mordechai; Li, Chun; Sofowora, Gbenga G; Friedman, Eitan A; Scheinin, Mika; Wood, Alastair J J; Stein, C Michael

    2011-04-01

    α(2A)-Adrenoceptors (α(2A)-ARs) have important roles in sympathetic cardiovascular regulation. Variants of ADRA2A affect gene transcription and expression and are associated with insulin release and risk for type 2 diabetes. We examined whether ADRA2A variants are also associated with cardiovascular responses to the selective α(2)-AR-agonist dexmedetomidine. Seventy-three healthy subjects participated in a placebo-controlled, single-blind study. After 3 infusions of placebo, subjects received 3 incremental infusions of dexmedetomidine (cumulative dose, 0.4 μg/kg). Primary outcomes were changes in systolic blood pressure (SBP) and plasma norepinephrine concentrations, measured as difference of the area-under-the-curve during placebo and dexmedetomidine infusions (ΔAUC). We used multiple linear regression analysis to examine the associations between 9 ADRA2A tagging variants and 5 inferred haplotypes and ΔAUC after adjustment for covariates. Homozygous carriers of rs553668 and the corresponding haplotype 4, previously associated with increased α(2A)-AR expression, had a 2.2-fold greater decrease in AUC(SBP) after dexmedetomidine (adjusted P=0.006); similarly, the maximum decrease in SBP was 24.7±8.1 mm Hg compared with 13.6±5.9 mm Hg in carriers of the wild-type allele (P=0.007). Carriers of haplotype 3, previously associated with reduced α(2A)-AR expression, had a 44% smaller decrease in AUC(SBP) (P=0.013). Haplotype information significantly improved the model predicting the decrease in SBP (P<0.001). There were similar but nonsignificant trends for diastolic blood pressure and heart rate. Genotypes were not significantly associated with norepinephrine responses. Common ADRA2A variants are associated with the hypotensive response to dexmedetomidine. Effects of specific variants/haplotypes in vivo are compatible with their known effects on gene expression in vitro.

  18. Reversible Unfolding of Rhomboid Intramembrane Proteases.

    PubMed

    Panigrahi, Rashmi; Arutyunova, Elena; Panwar, Pankaj; Gimpl, Katharina; Keller, Sandro; Lemieux, M Joanne

    2016-03-29

    Denaturant-induced unfolding of helical membrane proteins provides insights into their mechanism of folding and domain organization, which take place in the chemically heterogeneous, anisotropic environment of a lipid membrane. Rhomboid proteases are intramembrane proteases that play key roles in various diseases. Crystal structures have revealed a compact helical bundle with a buried active site, which requires conformational changes for the cleavage of transmembrane substrates. A dimeric form of the rhomboid protease has been shown to be important for activity. In this study, we examine the mechanism of refolding for two distinct rhomboids to gain insight into their secondary structure-activity relationships. Although helicity is largely abolished in the unfolded states of both proteins, unfolding is completely reversible for HiGlpG but only partially reversible for PsAarA. Refolding of both proteins results in reassociation of the dimer, with a 90% regain of catalytic activity for HiGlpG but only a 70% regain for PsAarA. For both proteins, a broad, gradual transition from the native, folded state to the denatured, partly unfolded state was revealed with the aid of circular dichroism spectroscopy as a function of denaturant concentration, thus arguing against a classical two-state model as found for many globular soluble proteins. Thermal denaturation has irreversible destabilizing effects on both proteins, yet reveals important functional details regarding substrate accessibility to the buried active site. This concerted biophysical and functional analysis demonstrates that HiGlpG, with a simple six-transmembrane-segment organization, is more robust than PsAarA, which has seven predicted transmembrane segments, thus rendering HiGlpG amenable to in vitro studies of membrane-protein folding. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  19. Insulin restores L-arginine transport requiring adenosine receptors activation in umbilical vein endothelium from late-onset preeclampsia.

    PubMed

    Salsoso, R; Guzmán-Gutiérrez, E; Sáez, T; Bugueño, K; Ramírez, M A; Farías, M; Pardo, F; Leiva, A; Sanhueza, C; Mate, A; Vázquez, C; Sobrevia, L

    2015-03-01

    Preeclampsia is associated with impaired placental vasodilation and reduced endothelial nitric oxide synthase (eNOS) activity in the foetoplacental circulation. Adenosine and insulin stimulate vasodilation in endothelial cells, and this activity is mediated by adenosine receptor activation in uncomplicated pregnancies; however, this activity has yet to be examined in preeclampsia. Early onset preeclampsia is associated with severe placental vasculature alterations that lead to altered foetus growth and development, but whether late-onset preeclampsia (LOPE) alters foetoplacental vascular function is unknown. Vascular reactivity to insulin (0.1-1000 nmol/L, 5 min) and adenosine (1 mmol/L, 5 min) was measured in KCl-preconstricted human umbilical vein rings from normal and LOPE pregnancies using a wire myograph. The protein levels of human cationic amino acid transporter 1 (hCAT-1), adenosine receptor subtypes, total and Ser¹¹⁷⁷- or Thr⁴⁹⁵-phosphorylated eNOS were detected via Western blot, and L-arginine transport (0-1000 μmol/L L-arginine, 3 μCi/mL L-[³H]arginine, 20 s, 37 °C) was measured in the presence or absence of insulin and adenosine receptor agonists or antagonists in human umbilical vein endothelial cells (HUVECs) from normal and LOPE pregnancies. LOPE increased the maximal L-arginine transport capacity and hCAT-1 and eNOS expression and activity compared with normal conditions. The A(2A) adenosine receptor (A(2A)AR) antagonist ZM-241385 blocked these effects of LOPE. Insulin-mediated umbilical vein ring relaxation was lower in LOPE pregnancies than in normal pregnancies and was restored using the A(2A)AR antagonist. The reduced foetoplacental vascular response to insulin may result from A(2A)AR activation in LOPE pregnancies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model.

    PubMed

    van der Pals, Jesper; Koul, Sasha; Andersson, Patrik; Götberg, Matthias; Ubachs, Joey F A; Kanski, Mikael; Arheden, Håkan; Olivecrona, Göran K; Larsson, Bengt; Erlinge, David

    2010-09-27

    Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. In anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability.

  1. Prediction of esophageal varices and variceal hemorrhage in patients with acute upper gastrointestinal bleeding.

    PubMed

    Rockey, Don C; Elliott, Alan; Lyles, Thomas

    2016-03-01

    In patients with upper gastrointestinal bleeding (UGIB), identifying those with esophageal variceal hemorrhage prior to endoscopy would be clinically useful. This retrospective study of a large cohort of patients with UGIB used logistic regression analyses to evaluate the platelet count, aspartate aminotransferase (AST) to platelet ratio index (APRI), AST to alanine aminotransferase (ALT) ratio (AAR) and Lok index (all non-invasive blood markers) as predictors of variceal bleeding in (1) all patients with UGIB and (2) patients with cirrhosis and UGIB. 2233 patients admitted for UGIB were identified; 1034 patients had cirrhosis (46%) and of these, 555 patients (54%) had acute UGIB due to esophageal varices. In all patients with UGIB, the platelet count (cut-off 122,000/mm(3)), APRI (cut-off 5.1), AAR (cut-off 2.8) and Lok index (cut-off 0.9) had area under the curve (AUC)s of 0.80 0.82, 0.64, and 0.80, respectively, for predicting the presence of varices prior to endoscopy. To predict varices as the culprit of bleeding, the platelet count (cut-off 69,000), APRI (cut-off 2.6), AAR (cut-off 2.5) and Lok Index (0.90) had AUCs of 0.76, 0.77, 0.57 and 0.73, respectively. Finally, in patients with cirrhosis and UGIB, logistic regression was unable to identify optimal cut-off values useful for predicting varices as the culprit bleeding lesion for any of the non-invasive markers studied. For all patients with UGIB, non-invasive markers appear to differentiate patients with varices from those without varices and to identify those with a variceal culprit lesion. However, these markers could not distinguish between a variceal culprit and other lesions in patients with cirrhosis. Copyright © 2016 American Federation for Medical Research.

  2. Sleep disorders in Latin-American children with asthma and/or allergic rhinitis and normal controls.

    PubMed

    Urrutia-Pereira, M; Solé, D; Chong Neto, H J; Acosta, V; Cepeda, A M; Álvarez-Castelló, M; Almendarez, C F; Lozano-Saenz, J; Sisul-Alvariza, J C; Rosario, N A; Castillo, A J; Valentin-Rostan, M; Badellino, H; Castro-Almarales, R L; González-León, M; Sanchez-Silot, C; Avalos, M M; Fernandez, C; Berroa, F; De la Cruz, M M; Sarni, R O S

    Asthma and/or allergic rhinitis have been associated with sleep disorders. The aim of this study was to evaluate sleep disorders in Latin-American children (4-10 years) from nine countries, with persistent asthma (A) and/or allergic rhinitis (AR) and in normal controls (C). Parents from 454 C children and 700 A and/or AR children followed up in allergy reference clinics completed the Children's Sleep Habits Questionnaire (CSHQ) which is a retrospective one-week questionnaire composed of 33 questions composed of seven subscales (bedtime resistance, sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing and daytime sleepiness). The total scale of CSHQ and the subscales were compared between groups C and A+AR, A (n=285) vs. AR (n=390), and between controlled A (CA, n=103) vs. partially controlled/uncontrolled A (UA, n=182). The comparison between C and A+AR showed no significant differences in age (6.7 years vs. 7.0 years, respectively), mean Body Mass Index and total scale of CSHQ (53.3 vs. 63.2, respectively) and the subscales were significantly higher in the A+AR group. Comparison between groups A and AR, except for sleep anxiety, showed significantly higher values for CSHQ total scale (66.9 vs. 61.0, respectively) and subscales for group A. The UA group showed significantly higher values for total CSHQ scale and subscales in comparison to CA (71.1 vs. 59.4, respectively). Latin-American children with asthma and/or allergic rhinitis showed sleep disorders identified by the CSHQ when compared to normal controls. Despite being treated, asthma causes sleep impairment, especially when uncontrolled. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

  3. 49 CFR 179.400-12 - Postweld heat treatment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Postweld heat treatment. 179.400-12 Section 179...-12 Postweld heat treatment. (a) Postweld heat treatment of the inner tank is not required. (b) The... postweld heat treated as prescribed in AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7 of...

  4. 49 CFR 179.400-12 - Postweld heat treatment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Postweld heat treatment. 179.400-12 Section 179...-12 Postweld heat treatment. (a) Postweld heat treatment of the inner tank is not required. (b) The... postweld heat treated as prescribed in AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7 of...

  5. 49 CFR 179.400-12 - Postweld heat treatment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Postweld heat treatment. 179.400-12 Section 179...-12 Postweld heat treatment. (a) Postweld heat treatment of the inner tank is not required. (b) The... postweld heat treated as prescribed in AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7 of...

  6. 49 CFR 179.400-12 - Postweld heat treatment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Postweld heat treatment. 179.400-12 Section 179...-12 Postweld heat treatment. (a) Postweld heat treatment of the inner tank is not required. (b) The... postweld heat treated as prescribed in AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7 of...

  7. 49 CFR 179.100-10 - Postweld heat treatment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Postweld heat treatment. 179.100-10 Section 179... Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.100-10 Postweld heat... heat treated as a unit in compliance with the requirements of AAR Specifications for Tank Cars...

  8. The heritability of vessel size of the pampiniform plexus as a means to assess the genetic component of varicocele

    USDA-ARS?s Scientific Manuscript database

    Ultrasonography of each testicle was used to capture a coronal-saggital image of the veins of the pampiniform plexus (PP) and the testicular artery of 239 boars at approximately 6 months of age. Three to 10 vessels of the PP were used to derive the average area of right PP vessels (AAR) and the aver...

  9. 78 FR 44189 - Petition for Modification of Single Car Air Brake Test Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ...] Petition for Modification of Single Car Air Brake Test Procedures In accordance with Part 232 of Title 49... Administration (FRA) per 49 CFR 232.307 to modify the single car air brake test procedures located in AAR Standard S-486, Code of Air Brake System Tests for Freight Equipment-- Single Car Test, and required...

  10. 49 CFR 171.7 - Reference material.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Intermodal Equipment, 1988, into § 174.55; 174.63. (3) AAR Specifications for Design, Fabrication and... Edition), into § 172.400a. (8) CGA Pamphlet C-8, Standard for Requalification of DOT-3HT Cylinder Design... Compressed Gas Cylinders at Time of Manufacture, 2001, Third Edition, into § 178.35. (10) CGA Pamphlet C-12...

  11. Noncombatant Evacuation Operations: Department of State’s Lessons Learned Program

    DTIC Science & Technology

    2016-06-10

    student author and do not necessarily represent the views of the U.S. Army Command and General Staff College or any other U.S. governmental agency...68 viii ACRONYMS AAR After Action Review CALL Center for Army Lessons Learned CMS Crisis Management Support CMU Crisis Management ...Knowledge Management Chart .......................................................................25 Figure 5. Organization Chart

  12. 49 CFR 232.603 - Design, interoperability, and configuration management requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... requirements. (a) General. A freight car or freight train equipped with an ECP brake system shall, at a minimum...) Approval. A freight train or freight car equipped with an ECP brake system and equipment covered by the AAR...) Configuration management. A railroad operating a freight train or freight car equipped with ECP brake systems...

  13. 49 CFR 232.603 - Design, interoperability, and configuration management requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... requirements. (a) General. A freight car or freight train equipped with an ECP brake system shall, at a minimum...) Approval. A freight train or freight car equipped with an ECP brake system and equipment covered by the AAR...) Configuration management. A railroad operating a freight train or freight car equipped with ECP brake systems...

  14. 49 CFR 232.603 - Design, interoperability, and configuration management requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... requirements. (a) General. A freight car or freight train equipped with an ECP brake system shall, at a minimum...) Approval. A freight train or freight car equipped with an ECP brake system and equipment covered by the AAR...) Configuration management. A railroad operating a freight train or freight car equipped with ECP brake systems...

  15. 49 CFR 232.603 - Design, interoperability, and configuration management requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... requirements. (a) General. A freight car or freight train equipped with an ECP brake system shall, at a minimum...) Approval. A freight train or freight car equipped with an ECP brake system and equipment covered by the AAR...) Configuration management. A railroad operating a freight train or freight car equipped with ECP brake systems...

  16. Cardiorespiratory responses and reduced apneic time to cold-water face immersion after high intensity exercise.

    PubMed

    Konstantinidou, Sylvia; Soultanakis, Helen

    2016-01-01

    Apnea after exercise may evoke a neurally mediated conflict that may affect apneic time and create a cardiovascular strain. The physiological responses, induced by apnea with face immersion in cold water (10 °C), after a 3-min exercise bout, at 85% of VO2max,were examined in 10 swimmers. A pre-selected 40-s apnea, completed after rest (AAR), could not be met after exercise (AAE), and was terminated with an agonal gasp reflex, and a reduction of apneic time, by 75%. Bradycardia was evident with immersion after both, 40-s of AAR and after AAE (P<0.05). The dramatic elevation of, systolic pressure and pulse pressure, after AAE, were indicative of cardiovascular stress. Blood pressure after exercise without apnea was not equally elevated. The activation of neurally opposing functions as those elicited by the diving reflex after high intensity exercise may create an autonomic conflict possibly related to oxygen-conserving reflexes stimulated by the trigeminal nerve, and those elicited by exercise. Copyright © 2015. Published by Elsevier B.V.

  17. Development and validation of a predictive model for the influences of selected product and process variables on ascorbic acid degradation in simulated fruit juice.

    PubMed

    Gabriel, Alonzo A; Cayabyab, Jochelle Elysse C; Tan, Athalie Kaye L; Corook, Mark Lester F; Ables, Errol John O; Tiangson-Bayaga, Cecile Leah P

    2015-06-15

    A predictive response surface model for the influences of product (soluble solids and titratable acidity) and process (temperature and heating time) parameters on the degradation of ascorbic acid (AA) in heated simulated fruit juices (SFJs) was established. Physicochemical property ranges of freshly squeezed and processed juices, and a previously established decimal reduction times of Escherichiacoli O157:H7 at different heating temperatures were used in establishing a Central Composite Design of Experiment that determined the combinations of product and process variable used in the model building. Only the individual linear effects of temperature and heating time significantly (P<0.05) affected AA reduction (%AAr). Validating systems either over- or underestimated actual %AAr with bias factors 0.80-1.20. However, all validating systems still resulted in acceptable predictive efficacy, with accuracy factor 1.00-1.26. The model may be useful in establishing unique process schedules for specific products, for the simultaneous control and improvement of food safety and quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Low Doses of Allyphenyline and Cyclomethyline, Effective against Morphine Dependence, Elicit an Antidepressant-like Effect

    PubMed Central

    2012-01-01

    This study demonstrated that cyclomethyline (2) and the corresponding enantiomers (R)-(−)-2 and (S)-(+)-2, displaying α2C-adrenoreceptor (AR) agonism/α2A-AR antagonism, similarly to allyphenyline (1) and its enantiomers, significantly decreased the naloxone-precipitated withdrawal symptoms in mice at very low doses. It also highlighted that such positive effects on morphine dependence can even be improved by additional serotoninergic 5-HT1A receptor (5-HT1A-R) activation. Indeed, 1 or the single (S)-(+)-1, 2, or both its enantiomers, all behaving as α2C-AR agonists/α2A-AR antagonists/5-HT1A-R agonists, alone and at the same low dose, improved morphine withdrawal syndrome and exerted a potent antidepressant-like effect. Therefore, considering the elevated comorbidity between opiate abuse and depressed mood and the benefit of these multifunctional compounds to both disorders, it is possible that they prove more efficacious and less toxic than a cocktail of drugs in managing opioid addiction. PMID:24900506

  19. Exact docking flight controller for autonomous aerial refueling with back-stepping based high order sliding mode

    NASA Astrophysics Data System (ADS)

    Su, Zikang; Wang, Honglun; Li, Na; Yu, Yue; Wu, Jianfa

    2018-02-01

    Autonomous aerial refueling (AAR) exact docking control has always been an intractable problem due to the strong nonlinearity, the tight coupling of the 6 DOF aircraft model and the complex disturbances of the multiple environment flows. In this paper, the strongly coupled nonlinear 6 DOF model of the receiver aircraft which considers the multiple flow disturbances is established in the affine nonlinear form to facilitate the nonlinear controller design. The items reflecting the influence of the unknown flow disturbances in the receiver dynamics are taken as the components of the "lumped disturbances" together with the items which have no linear correlation with the virtual control variables. These unmeasurable lumped disturbances are estimated and compensated by a specially designed high order sliding mode observer (HOSMO) with excellent estimation property. With the compensation of the estimated lumped disturbances, a back-stepping high order sliding mode based exact docking flight controller is proposed for AAR in the presence of multiple flow disturbances. Extensive simulation results demonstrate the feasibility and superiority of the proposed docking controller.

  20. 49 CFR 171.7 - Reference material.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., 1988, into § 174.55; 174.63. (3) AAR Specifications for Design, Fabrication and Construction of Freight... Edition), into § 172.400a. (8) CGA Pamphlet C-8, Standard for Requalification of DOT-3HT Cylinder Design... Compressed Gas Cylinders at Time of Manufacture, 2001, Third Edition, into § 178.35. (10) CGA Pamphlet C-12...

  1. Squad Overmatch Study: Training Human Dimension to Enhance Performance

    DTIC Science & Technology

    2014-09-30

    warrior skills training programs across the Soldier training continuum, using adult learning strategies with facilitated and self -guided After Action...warrior skills AARs were supplemented with facilitated and self -guided ASA and resilience discussions, reinforcing previously learned skills. 4...coaching and feedback with guided team self -correction Implementation Strategy 1. Single Army HD Requirements Integration Manager: The Big

  2. 77 FR 41473 - Proposed Technical Standard Order (TSO)-C126b, 406 MHz Emergency Locator Transmitters (ELT) and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... antenna connection to sever, rendering the ELT ineffective and severely impacting the performance of the... AAR-11-03: The antenna cable was severed from the ELT when the ELT slipped out of the hook and loop... NTSB ID WPR10FA273: The antenna cable was severed from the ELT when the ELT slipped out of the hook and...

  3. 49 CFR 179.220-18 - Bottom outlets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...-shaped breakage groove shall be cut (not cast) in the upper part of the outlet nozzle at a point... nozzle extends below the bottom of the outer shell, a V-shaped breakage groove shall be cut (not cast) in... projection of the bottom outlet equipment may not be more than that allowed by appendix E of the AAR...

  4. Spatial and temporal modelling of fluvial aggradation in the Hasli Valley (Swiss Alps) during the last 1300 years

    NASA Astrophysics Data System (ADS)

    Llorca, Jaime; Schulte, Lothar; Carvalho, Filipe

    2016-04-01

    The Haslital delta (upper Aare River catchment, Bernese Alps) progradated into the Lake Brienz after the retreat of the Aare Glacier (post-LGM). Present delta plain geomorphology and spatial distribution of sedimentary facies result from historical fluvial dynamics and aggradation. Over centuries, local communities have struggled to control the Aare floods and to mitigate their effects on the floodplain (by means of raising artificial levees, channelizing the course, creating an underground drainage network, constructing dams at the basin headwaters). This study focuses on the spatial and temporal evolution of sediment dynamics of the floodplain by analyzing fluvial sedimentary records . The internal variability of lithostratigraphic sequences is a key issue to understand hydrological processes in the basin under the effect of environmental and anthropogenic changes of the past. The floodplain lithostratigraphy was reconstructed by coring alongside four cross-sections; each one is composed of more than 25 shallow boreholes (2 m deep) and two long drillings (variable depth, up to 9 m). The chronostratigraphical models were obtained by AMS 14C dating, and information of paleofloods and channel migration were reconstructed from historical sources (Schulte et al., 2015). The identification of different sedimentary facies, associated with the fluvial architecture structures, provides information on variations of vertical and lateral accretion processes (Houben, 2007). The location and geometry of buried channel-levee facies (gravel and coarse sand layers) indicate a significant mobility of the riverbed of the Hasli-Aare river, following an oscillatory pattern during the last millennia. Furthermore, fine sedimentary deposits and peat layers represent the existence of stable areas where floods have a low incidence. Once the different types of deposits were identified, aggradation rates were estimated in order to determine the spatial variability of the accumulation

  5. Overdeepened glacigenic landforms in Lake Thun (Switzerland) revealed by a multichannel reflection seismic survey

    NASA Astrophysics Data System (ADS)

    Fabbri, Stefano; Herwegh, Marco; Schlunegger, Fritz; Hübscher, Christian; Weiss, Benedikt J.; Schmelzbach, Cédric; Horstmeyer, Heinrich; Buechi, Marius W.; Anselmetti, Flavio S.

    2016-04-01

    Recently acquired high-resolution multibeam bathymetry, in combination with a 2D multichannel reflection seismic campaign on perialpine Lake Thun (Switzerland) reveals new insights into the diverse geometry of the lake basin and a so far unknown subaquatic moraine crest with unprecedented clarity. These new data will improve our comprehension concerning the retreat phases of the Aare glacier, the morphology of its proximal deposits and the facies architecture of the subglacial units. The overdeepened basin of Lake Thun was formed by a combination of tectonically predefined weak zones and glacial erosion during the last glacial periods. The new data indicate that below the outermost edge of a morphologically distinct platform in the south eastern part of the lake basin, a ridge structure marked by strong reflection amplitudes occurs. This structure is interpreted as a subaquatic terminal moraine crest, most likely created by a slightly advancing or stagnant grounded Aare glacier during its major retreating phase. The terminal moraine smoothly transforms downstream into well distinguishable foresets with internally recognisable layering, which dip steeply towards the deepest part of the basin, eventually transforming into bottomsets. This depositional sequence formed by the fore- and bottomsets represents ˜50% of the overall sediment volume that fills the basin and was deposited while the glacier was stagnant, interpreted to represent a rather short period of time of a few hundreds of years. This sequence is overlain by lacustrine deposits formed by late-glacial and Holocene laminated muds comprising intercalated turbidites (Wirth et al. 2011). Little is known about the exact timing and behaviour of retreating glaciers between their recessional phase from the Alpine foreland to the deglaciation of the inner-Alpine ice cap, mostly due to the lack of well-developed moraines that indicate glacial stabilization or slight readvance. Findings from pollen analyses by

  6. Security Strategy of the Bureau of Diplomatic Security.

    DTIC Science & Technology

    2011-06-10

    Williams, M.A. , Member John A. Dyson, MBA , Member Gregory Scott Hospodor, Ph.D Accepted this 10th day of June 2011 by...ACRONYMS AAR After Action Review ASOS Advance Security Overseas Seminar ATA Antiterrorism Assistance Program BRSO Regional Security Officer Course ...BSAC Basic Special Agent Course DS Bureau of Diplomatic Security FACT Foreign Affairs Counter Threat FAH Foreign Affairs Handbook FAM Foreign

  7. China’s Emerging Capabilities in Energy Technology Innovation and Development

    DTIC Science & Technology

    2015-01-22

    management of tempo, scaling, and cost reduction. For particularly complex energy technology systems, such as civilian nuclear power plants , the...technology systems, such as civilian nuclear power plants , the greatest challenges often involve not so much new technology development (a...are far more complex phenomena unfolding than simply technology transfer, duplication, and mimicry . Our work has opened up a series of new

  8. Maximum Grasping Reach of Operators Possessing Functional Impairments of the Upper Extremities.

    DTIC Science & Technology

    1978-12-01

    ADDRESS 10. PROGRAM ELEMENT, PROJECT, TASK AFITStudent at: Texas A&M University AREA & WORK UNIT NUMBERS II. CONTROLLING OFFICENA E AND AD_. . 12...RELEASE AFR 190.172 Ja e I 10, t USAF 23 SEP 1980 , ’ 1"lic Aar* e IS. SUPPLEMENTARY NOTES Approved for public release; IAW AFR 190-17 Air Force...C .. .... ..... ..... .... 141 APPENDIX D .. ... ...... ..... .... 184 APPENDIX E .. ... ..... ...... .... 187 APPENDIX F .. .... ..... ..... .... 189

  9. 49 CFR 179.102-1 - Carbon dioxide, refrigerated liquid.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... and anchorage of tanks must be made of carbon steel conforming to ASTM A 516/A 516M (IBR, see § 171.7 of this subchapter), Grades 55, 60, 65, or 70, or AAR Specification TC 128-78, Grade B. The ASTM A 516/A 516M plate must also meet the Charpy V-Notch test requirements of ASTM A 20/A 20M (see table 16...

  10. Global Climate Change - U.S. Economic and National Security Opportunity

    DTIC Science & Technology

    2009-03-20

    The most recent findings of the Intergovernmental Panel on Climate Change (IPCC) state that the current trajectory of greenhouse gas (GHG) emissions...challenges and opportunities for the United States as they balance national security and economic interests. The effects of climate change could act as a...are various opportunities associated with climate change including opening arctic navigational channels and the vast oil and natural gas resources

  11. Leadership, Management, and Organization for National Security Space: Report to Congress of the Independent Assessment Panel on the Organization and Management of National Security Space

    DTIC Science & Technology

    2008-07-01

    Engineering. General Ronald R. Fogleman, United States Air Force - Retired General Ron Fogleman is the Chairman of the Board of The Durango ...serves on the board of directors for AAR Corp, Alpha Security, Alliant Techsystems, First National Bank of Durango , Integrated Data Corporation...headquartered in McLean, Virginia. He is based in Colorado Springs. Specializing in strategic planning and the management of complex organizations

  12. After Action Review Tools For Team Training with Chat Communications

    DTIC Science & Technology

    2009-11-01

    collaborative learning environments. The most relevant work is being done by the CALO ( Cognitive Agent that Learns and Organizes) project, a joint...emoticons, and other common stylistic practices. To a lesser degree, some research has yielded methods and tools to analyze or visualize chat...information sources, and overall cognitive effort. AAR Challenges The most significant challenge to conducting an effective after action review of

  13. Low-Torque Seal Development

    NASA Technical Reports Server (NTRS)

    Lattime, Scott B.; Borowski, Richard

    2009-01-01

    The EcoTurn Class K production prototypes have passed all AAR qualification tests and received conditional approval. The accelerated life test on the second set of seals is in progress. Due to the performance of the first set, no problems are expected.The seal has demonstrated superior performance over the HDL seal in the test lab with virtually zero torque and excellent contamination exclusion and grease retention.

  14. Serial millisecond crystallography of membrane and soluble protein microcrystals using synchrotron radiation

    PubMed Central

    Conrad, Chelsie E.; Nelson, Garrett; Stander, Natasha; Zatsepin, Nadia A.; Zook, James; Zhu, Lan; Geiger, James; Chun, Eugene; Kissick, David; Hilgart, Mark C.; Ogata, Craig; Ishchenko, Andrii; Nagaratnam, Nirupa; Roy-Chowdhury, Shatabdi; Coe, Jesse; Subramanian, Ganesh; Schaffer, Alexander; Ketwala, Gihan; Venugopalan, Nagarajan; Xu, Shenglan; Corcoran, Stephen; Ferguson, Dale; Weierstall, Uwe; Spence, John C. H.; Cherezov, Vadim; Fromme, Petra; Fischetti, Robert F.; Liu, Wei

    2017-01-01

    Crystal structure determination of biological macromolecules using the novel technique of serial femtosecond crystallography (SFX) is severely limited by the scarcity of X-ray free-electron laser (XFEL) sources. However, recent and future upgrades render microfocus beamlines at synchrotron-radiation sources suitable for room-temperature serial crystallography data collection also. Owing to the longer exposure times that are needed at synchrotrons, serial data collection is termed serial millisecond crystallography (SMX). As a result, the number of SMX experiments is growing rapidly, with a dozen experiments reported so far. Here, the first high-viscosity injector-based SMX experiments carried out at a US synchrotron source, the Advanced Photon Source (APS), are reported. Microcrystals (5–20 µm) of a wide variety of proteins, including lysozyme, thaumatin, phycocyanin, the human A2A adenosine receptor (A2AAR), the soluble fragment of the membrane lipoprotein Flpp3 and proteinase K, were screened. Crystals suspended in lipidic cubic phase (LCP) or a high-molecular-weight poly(ethylene oxide) (PEO; molecular weight 8 000 000) were delivered to the beam using a high-viscosity injector. In-house data-reduction (hit-finding) software developed at APS as well as the SFX data-reduction and analysis software suites Cheetah and CrystFEL enabled efficient on-site SMX data monitoring, reduction and processing. Complete data sets were collected for A2AAR, phycocyanin, Flpp3, proteinase K and lysozyme, and the structures of A2AAR, phycocyanin, proteinase K and lysozyme were determined at 3.2, 3.1, 2.65 and 2.05 Å resolution, respectively. The data demonstrate the feasibility of serial millisecond crystallography from 5–20 µm crystals using a high-viscosity injector at APS. The resolution of the crystal structures obtained in this study was dictated by the current flux density and crystal size, but upcoming developments in beamline optics and the planned APS

  15. Stargardt macular dystrophy: common ABCA4 mutations in South Africa—establishment of a rapid genetic test and relating risk to patients

    PubMed Central

    Nossek, Christel A.; Greenberg, L. Jacquie; Ramesar, Rajkumar S.

    2012-01-01

    Purpose Based on the previous indications of founder ATP-binding cassette sub-family A member 4 gene (ABCA4) mutations in a South African subpopulation, the purpose was to devise a mechanism for identifying common disease-causing mutations in subjects with ABCA4-associated retinopathies (AARs). Facilitating patient access to this data and determining the frequencies of the mutations in the South African population would enhance the current molecular diagnostic service offered. Methods The majority of subjects in this study were of Caucasian ancestry and affected with Stargardt macular dystrophy. The initial cohort consisted of DNA samples from 181 patients, and was screened using the ABCR400 chip. An assay was then designed to screen a secondary cohort of 72 patients for seven of the most commonly occurring ABCA4 mutations in this population. A total of 269 control individuals were also screened for the seven ABCA4 mutations. Results Microarray screening results from a cohort of 181 patients affected with AARs revealed that seven ABCA4 mutations (p.Arg152*, c.768G>T, p.Arg602Trp, p.Gly863Ala, p.Cys1490Tyr, c.5461–10T>C, and p.Leu2027Phe) occurred at a relatively high frequency. The newly designed genetic assay identified two of the seven disease-associated mutations in 28/72 patients in a secondary patient cohort. In the control cohort, 12/269 individuals were found to be heterozygotes, resulting in an estimated background frequency of these mutations in this particular population of 4.46 per 100 individuals. Conclusions The relatively high detection rate of seven ABCA4 mutations in the primary patient cohort led to the design and subsequent utility of a multiplex assay. This assay can be used as a viable screening tool and to reduce costs and laboratory time. The estimated background frequency of the seven ABCA4 mutations, together with the improved diagnostic service, could be used by counselors to facilitate clinical and genetic management of South African

  16. Serial millisecond crystallography of membrane and soluble protein microcrystals using synchrotron radiation

    DOE PAGES

    Martin-Garcia, Jose M.; Conrad, Chelsie E.; Nelson, Garrett; ...

    2017-05-24

    Crystal structure determination of biological macromolecules using the novel technique of serial femtosecond crystallography (SFX) is severely limited by the scarcity of X-ray free-electron laser (XFEL) sources. However, recent and future upgrades render microfocus beamlines at synchrotron-radiation sources suitable for room-temperature serial crystallography data collection also. Owing to the longer exposure times that are needed at synchrotrons, serial data collection is termed serial millisecond crystallography (SMX). As a result, the number of SMX experiments is growing rapidly, with a dozen experiments reported so far. Here, the first high-viscosity injector-based SMX experiments carried out at a US synchrotron source, the Advancedmore » Photon Source (APS), are reported. Microcrystals (5–20 µm) of a wide variety of proteins, including lysozyme, thaumatin, phycocyanin, the human A 2A adenosine receptor (A 2AAR), the soluble fragment of the membrane lipoprotein Flpp3 and proteinase K, were screened. Crystals suspended in lipidic cubic phase (LCP) or a high-molecular-weight poly(ethylene oxide) (PEO; molecular weight 8 000 000) were delivered to the beam using a high-viscosity injector. In-house data-reduction (hit-finding) software developed at APS as well as the SFX data-reduction and analysis software suites Cheetah and CrystFEL enabled efficient on-site SMX data monitoring, reduction and processing. Complete data sets were collected for A 2AAR, phycocyanin, Flpp3, proteinase K and lysozyme, and the structures of A 2AAR, phycocyanin, proteinase K and lysozyme were determined at 3.2, 3.1, 2.65 and 2.05 Å resolution, respectively. The data demonstrate the feasibility of serial millisecond crystallography from 5–20 µm crystals using a high-viscosity injector at APS. The resolution of the crystal structures obtained in this study was dictated by the current flux density and crystal size, but upcoming developments in beamline optics and the planned APS

  17. Serial millisecond crystallography of membrane and soluble protein microcrystals using synchrotron radiation

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

    Martin-Garcia, Jose M.; Conrad, Chelsie E.; Nelson, Garrett

    Crystal structure determination of biological macromolecules using the novel technique of serial femtosecond crystallography (SFX) is severely limited by the scarcity of X-ray free-electron laser (XFEL) sources. However, recent and future upgrades render microfocus beamlines at synchrotron-radiation sources suitable for room-temperature serial crystallography data collection also. Owing to the longer exposure times that are needed at synchrotrons, serial data collection is termed serial millisecond crystallography (SMX). As a result, the number of SMX experiments is growing rapidly, with a dozen experiments reported so far. Here, the first high-viscosity injector-based SMX experiments carried out at a US synchrotron source, the Advancedmore » Photon Source (APS), are reported. Microcrystals (5–20 µm) of a wide variety of proteins, including lysozyme, thaumatin, phycocyanin, the human A 2A adenosine receptor (A 2AAR), the soluble fragment of the membrane lipoprotein Flpp3 and proteinase K, were screened. Crystals suspended in lipidic cubic phase (LCP) or a high-molecular-weight poly(ethylene oxide) (PEO; molecular weight 8 000 000) were delivered to the beam using a high-viscosity injector. In-house data-reduction (hit-finding) software developed at APS as well as the SFX data-reduction and analysis software suites Cheetah and CrystFEL enabled efficient on-site SMX data monitoring, reduction and processing. Complete data sets were collected for A 2AAR, phycocyanin, Flpp3, proteinase K and lysozyme, and the structures of A 2AAR, phycocyanin, proteinase K and lysozyme were determined at 3.2, 3.1, 2.65 and 2.05 Å resolution, respectively. The data demonstrate the feasibility of serial millisecond crystallography from 5–20 µm crystals using a high-viscosity injector at APS. The resolution of the crystal structures obtained in this study was dictated by the current flux density and crystal size, but upcoming developments in beamline optics and the planned APS

  18. Computational Insights into the High-Fidelity Catalysis of Aminoacyl-tRNA Synthetases

    NASA Astrophysics Data System (ADS)

    Aboelnga, Mohamed M.

    Obtaining insights into the catalytic function of enzymes is an important area of research due to their widespread applications in the biotechnology and pharmaceutical industries. Among these enzymes, the aminoacyl-tRNA synthetases (aaRSs) are known for their remarkable fidelity in catalyzing the aminoacylation reactions of tRNA in protein biosynthesis. Despite the exceptional execution of this critical function, mechanistic details of the reactions catalyzed by aminoacyl-tRNA synthetases remain elusive demonstrating the obvious need to explore their remarkable chemistry. During the PhD studies reported in this thesis the mechanism of aminoacylation, pre?transfer editing and post?transfer editing catalyzed by different aaRS have been established using multi-scale computational enzymology. In the first two chapters a detailed information about aaRS and the addressed questions was given in addition to an overview of the used computational methodology currently used to investigate the enzymatic mechanisms. The aminoacylation mechanism of threonine by Threonyl-tRNA synthetases, glutamine by Glutaminyl-tRNA synthetases and glutamate by Glutamyl-tRNA synthetases have been clearly unveiled in chapter 3 and 4. Also, valuable information regarding the role of cofactors and active site residues has been obtained. While investigating the post-transfer editing mechanisms, which proceed in a remote and distinct active site, two different scenarios were experimentally suggested for two types of threonyl-tRNA synthetase species to correct the misacylation of the structurally related serine. We explored these two mechanisms as in chapters 5 and 6. Moreover, the synthetic site in which the aminoacylation reaction is catalyzed, is also responsible for a second type of proofreading reaction called pre-transfer editing mechanism. In chapter 7, this latter mechanism has been elucidated for both Seryl-tRNA synthetases and Isoleucyl-tRNA synthetases against their non-cognate substrates

  19. Exercise Black Skies 2008: Enhancing Live Training Through Virtual Preparation -- Part Two: An Evaluation of Tools and Techniques

    DTIC Science & Technology

    2009-06-01

    visualisation tool. These tools are currently in use at the Surveillance and Control Training Unit (SACTU) in Williamtown, New South Wales, and the School...itself by facilitating the brevity and sharpness of learning points. The playback of video and audio was considered an extremely useful method of...The task assessor’s comments were supported by wall projections and audio replays of relevant mission segments that were controlled by an AAR

  20. An Exploration of Cohesion in the Land of Combat Service Support

    DTIC Science & Technology

    1991-12-18

    the group AAR the soldier finds that the companions he could not see were doing the same things that he was. Leaders discover actions of subordinates...seventy-eight years, and many wars ago. 39 ENDOUES. £ William Shakespeare , Tie Complete Works of William Shakespeare . (London: Octopus Books, 1986), 478...Beverly Hill, CA: Sage Publications, 1980. Shakespeare , William. The ComDlete Works of William Shakespeare . London: Octopus Books, 1985. Simpkin

  1. Minimizing Actuator-Induced Residual Error in Active Space Telescope Primary Mirrors

    DTIC Science & Technology

    2010-09-01

    actuator geometry, and rib-to-facesheet intersection geometry are exploited to achieve improved performance in silicon carbide ( SiC ) mirrors . A...are exploited to achieve improved performance in silicon carbide ( SiC ) mirrors . A parametric finite element model is used to explore the trade space...MOST) finite element model. The move to lightweight actively-controlled silicon carbide ( SiC ) mirrors is traced back to previous generations of space

  2. Construction Management Module: Contingency Contracting Synergistic Approach Integrating Joint Capabilities for USSOCOM

    DTIC Science & Technology

    2010-01-29

    mr_if`=mlif`v - ix - k^s^i=mlpqdo^ar^qb=p`elli= Acronym Listing AAR After-action Report ACC Acquisition Community Connection ADDIE Analyze...J3 Operations J4 Logistics J5 Plans J6 Communications J8 Programming and Comptroller J&A Justification and Approval JARB Joint...Due to geographical and communication constraints, the sample of informants was limited to 20 current USSOCOM personnel. However, the

  3. Dynamic Testing and Automatic Repair of Reconfigurable Wiring Harnesses

    DTIC Science & Technology

    2006-11-27

    Switch An M ×N grid of switches configured to provide a M -input, N -output routing network. Permutation Network A permutation network performs an...wiring reduces the effective advantage of their reduced switch count, particularly when considering that regular grids (crossbar switches being a...are connected to. The outline circuit shown in Fig. 20 shows how a suitable ‘discovery probe’ might be implemented. The circuit shows a UART

  4. Automated Chat Thread Analysis: Untangling the Web

    DTIC Science & Technology

    2010-01-01

    delays, distractions, errant information sources, and overall cognitive effort. The most significant challenge to conducting an effective after...to emphasize. Thus, the goal is to develop a tool that serves as a cognitive aid to instructors developing an After-Action Review (AAR). Our...work is being done by the “ Cognitive Agent that Learns and Organizes” (CALO) project, a joint effort between SRI and Stanford University’s Center for

  5. Anti-disturbance rapid vibration suppression of the flexible aerial refueling hose

    NASA Astrophysics Data System (ADS)

    Su, Zikang; Wang, Honglun; Li, Na

    2018-05-01

    As an extremely dangerous phenomenon in autonomous aerial refueling (AAR), the flexible refueling hose vibration caused by the receiver aircraft's excessive closure speed should be suppressed once it appears. This paper proposed a permanent magnet synchronous motor (PMSM) based refueling hose servo take-up system for the vibration suppression of the flexible refueling hose. A rapid back-stepping based anti-disturbance nonsingular fast terminal sliding mode (NFTSM) control scheme with a specially established finite-time convergence NFTSM observer is proposed for the PMSM based hose servo take-up system under uncertainties and disturbances. The unmeasured load torque and other disturbances in the PMSM system are reconstituted by the NFTSM observer and to be compensated during the controller design. Then, with the back-stepping technique, a rapid anti-disturbance NFTSM controller is proposed for the PMSM angular tracking to improve the tracking error convergence speed and tracking precision. The proposed vibration suppression scheme is then applied to PMSM based hose servo take-up system for the refueling hose vibration suppression in AAR. Simulation results show the proposed scheme can suppress the hose vibration rapidly and accurately even the system is exposed to strong uncertainties and probe position disturbances, it is more competitive in tracking accuracy, tracking error convergence speed and robustness.

  6. SMALL ACIDIC PROTEIN1 acts with RUB modification components, the COP9 signalosome, and AXR1 to regulate growth and development of Arabidopsis.

    PubMed

    Nakasone, Akari; Fujiwara, Masayuki; Fukao, Yoichiro; Biswas, Kamal Kanti; Rahman, Abidur; Kawai-Yamada, Maki; Narumi, Issay; Uchimiya, Hirofumi; Oono, Yutaka

    2012-09-01

    Previously, a dysfunction of the SMALL ACIDIC PROTEIN1 (SMAP1) gene was identified as the cause of the anti-auxin resistant1 (aar1) mutant of Arabidopsis (Arabidopsis thaliana). SMAP1 is involved in the response pathway of synthetic auxin, 2,4-dichlorophenoxyacetic acid, and functions upstream of the auxin/indole-3-acetic acid protein degradation step in auxin signaling. However, the exact mechanism by which SMAP1 functions in auxin signaling remains unknown. Here, we demonstrate that SMAP1 is required for normal plant growth and development and the root response to indole-3-acetic acid or methyl jasmonate in the auxin resistant1 (axr1) mutation background. Deletion analysis and green fluorescent protein/glutathione S-transferase pull-down assays showed that SMAP1 physically interacts with the CONSTITUTIVE PHOTOMORPHOGENIC9 SIGNALOSOME (CSN) via the SMAP1 F/D region. The extremely dwarf phenotype of the aar1-1 csn5a-1 double mutant confirms the functional role of SMAP1 in plant growth and development under limiting CSN functionality. Our findings suggest that SMAP1 is involved in the auxin response and possibly in other cullin-RING ubiquitin ligase-regulated signaling processes via its interaction with components associated with RELATED TO UBIQUITIN modification.

  7. Relation between lifespan polytrauma typologies and post-trauma mental health.

    PubMed

    Contractor, Ateka A; Brown, Lily A; Weiss, Nicole H

    2018-01-01

    Most individuals experience more than one trauma. Hence, it is important to consider the count and types of traumas (polytraumatization) in relation to post-trauma mental health. The current study examined the relation of polytraumatization patterns to PTSD clusters (intrusions, avoidance, negative alterations in cognitions and mood [NACM], and alterations in arousal and reactivity [AAR]), depression, and impulsivity facets (lack of perseverance, lack of premeditation, negative urgency, sensation seeking) using a web-based sample of 346 participants. Age, gender, race, and ethnicity were covariates. Results of latent class analyses indicated a three-class solution: Low Experience, Moderate Experience - Predominent Threat/Indirect PTEs (Moderate Experience), and High Experience - Predominant Interpersonal PTEs (High/Interpersonal). Multinomial logistic regression results indicated that ethnicity and gender were significant covariates in predicting Low versus High/Interpersonal Class, and Moderate Experience versus High/Interpersonal Class membership, respectively. The High/Interpersonal Class had higher scores on most PTSD clusters, depression, and the impulsivity facets of lack of perseverance and negative urgency compared to the other classes. The Low and Moderate Experience Classes differed on PTSD's avoidance and AAR clusters (lower in the former). Individuals exposed to multiple PTE types, particularly interpersonal traumas, may be at risk for more severe post-trauma symptoms. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Reconstruction of peak water levels, peak discharges and long-term occurrence of extreme- as well as smaller pre-instrumental flood events of river Aare, Limmat, Reuss, Rhine and Saane in Switzerland. Part II.

    NASA Astrophysics Data System (ADS)

    Tuttenuj, Daniel; Wetter, Oliver

    2016-04-01

    contained 54 Rhine flood events, whereas chroniclers and annalists only recorded seven floods during the same period. This is a ratio of almost eight to one. This large difference points to the significantly sharper "observation skills" of the account books towards smaller floods, which may be explained by the fact that bridges can be endangered by relatively small floods because of driftwood, whereas it is known that chroniclers or annalists were predominantly focussing on spectacular (extreme) flood events. We [Oliver Wetter and Daniel Tuttenuj] are now able to present first preliminary results of reconstructed peak water levels and peak discharges of pre instrumental river Aare-, Emme-, Limmat-, Reuss-, Rhine- and Saane floods. These first results clearly show the strengths as well as the limits of the data and method used, depending mainly on the river types. Of the above mentioned rivers only the floods of river Emme could not be reconstructed whereas the long-term development of peak water levels and peak discharges of the other rivers clearly correlate with major local and supra-regional Swiss flood corrections over time. PhD student Daniel Tuttenuj is going to present the results of river Emme and Saane, whereas Dr Oliver Wetter is going to present the results for the other rivers and gives a first insight on long-term recurring periods of smaller river Birs, Birsig, Rhine and Wiese flood events based on the analysis of the weekly led account books "Wochenausgabenbücher der Stadt Basel" (see Abstract Oliver Wetter).

  9. Reconstruction of peak water levels, peak discharges and long-term occurrence of extreme- as well as smaller pre-instrumental flood events of river Aare, Limmat, Reuss, Rhine and Saane in Switzerland. Part I

    NASA Astrophysics Data System (ADS)

    Wetter, Oliver; Tuttenuj, Daniel

    2016-04-01

    systematically analysed the period from 1446-1542 and could prove a large number of pre-instrumental flood events of river Rhine, Birs, Birsig and Wiese in Basel. All in all the weekly led account books contained 54 Rhine flood events, whereas chroniclers and annalists only recorded seven floods during the same period. This is a ratio of almost eight to one. This large difference points to the significantly sharper "observation skills" of the account books towards smaller floods, which may be explained by the fact that bridges can be endangered by relatively small floods because of driftwood, whereas it is known that chroniclers or annalists were predominantly focussing on spectacular (extreme) flood events. We [Oliver Wetter and Daniel Tuttenuj] are now able to present first preliminary results of reconstructed peak water levels and peak discharges of pre instrumental river Aare-, Emme-, Limmat-, Reuss-, Rhine- and Saane floods. These first results clearly show the strengths as well as the limits of the data and method used, depending mainly on the river types. Of the above mentioned rivers only the floods of river Emme could not be reconstructed whereas the long-term development of peak water levels and peak discharges of the other rivers clearly correlate with major local and supra-regional Swiss flood corrections over time. PhD student Daniel Tuttenuj is going to present the results for river Emme and Saane (see Abstract Daniel Tuttenuj), whereas Dr Oliver Wetter is going to present the results for the other rivers and gives a first insight on long-term recurring periods of smaller river Birs-, Birsig-, Rhine- and Wiese flood events based on the analysis of the weekly led account books "Wochenausgabenbücher der Stadt Basel" (see also Abstract of Daniel Tuttenuj).

  10. Oscillations in a Forward-Facing Cavity Measured Using Laser-Differential Interferometry in a Hypersonic Quiet Tunnel

    DTIC Science & Technology

    2007-12-11

    and behind the normal 5 Figure 2.1: Diagram of noise radiated from boundary layer transition on the nozzle wall shock of several pitot probes and a...are lower than those measured with the 0.067 in.-dia. pitot probe because the pressure fluctuations in the subsonic region behind the normal shock are...in.-dia. pitot probe before repolishing nozzle . . . . . . . . . . . . . . . . . . 16 2.10 Freestream noise level in the PQFLT measured with 1 in

  11. Journal of Special Operations Medicine, Volume 7, Edition 1

    DTIC Science & Technology

    2007-01-01

    SOMA through www.somaonline.org or contact MSG Russell Justice at justicer@earthlink.net. SOMA pro - vides a very valuable means of obtaining SOF...battlefield. The committee now has representation from all the Serv- ices and is busy deciding which way it needs to pro - ceed. There should be a...medical lessons learned and unit after actions reports (AARs) that con - tain combat mission needs has been a discussed item; this has been

  12. National Training Center Performance Trends for the Maneuver Operating System: Relationship to Training Doctrine

    DTIC Science & Technology

    1988-04-01

    Action Reviews (AAR) after each exercise . This information is synthesized in the THP, as is a sumary of Performance Trends for the entire fourteen...most frequently to least frequently commented upon across THPs. The actual number of times an issue was commented upon, either postively or...positions". "Dispersion of the positions" was some- times inadequate and units "failed to reinforce their positions with obstacles". "Utilization of

  13. Revisiting COIN Theory and Instruction

    DTIC Science & Technology

    2009-03-13

    Light ning II PE (12-24 Dec) B-10* Analy st Note book/ ARC GIS/ OP Dese rt Light ning II PE B-9...3 Mod B Final Test OP Deser t Light ning II PE (BUB 4) Mod B AAR B-16* Quiz 3 OP Deser t Light ning...Dec) (BUB 3 PMB) Quiz 3 Study Focus B-13* OP Desert Light ning II PE (BUB 2 Bn MB) B-11*

  14. Aircraft Accident Report; Uncontrolled Impact with Terrain, Fine Airlines Flight 101, Douglas DC-8-61, N27UA, Miami, Florida, August 7, 1997

    DTIC Science & Technology

    1998-06-16

    Transcolombiana de Carga ATI Air Transport International ATOS Air Transportation Oversight System ATP airline transport pilot CAM cockpit area microphone...495,000 fine against Aero Transcolombiana de Carga (ATC) for operating a DC-8-51 "over the weight limits set forth in its FAA-approved flight manual...PB98-910402 NTSB/AAR-98/02 DCA97MA059 NATIONAL TRANSPORTATION SAFETY BOARD WASHINGTON, D.C. 20594 AIRCRAFT ACCIDENT REPORT c>C== UNCONTROLLED IMPACT

  15. Exploratory Multivariate Analysis. A Graphical Approach.

    DTIC Science & Technology

    1981-01-01

    Gnanadesikan , 1977) but we feel that these should be used with great caution unless one really has good reason to believe that the data came from such a...are referred to Gnanadesikan (1977). The present author hopes that the convenience of a single summary or significance level will not deter his readers...fit of a harmonic model to meteorological data. (In preparation). Gnanadesikan , R. (1977). Methods for Statistical Data Analysis of Multivariate

  16. USSR Report, Military Affairs.

    DTIC Science & Technology

    1986-09-02

    Monitoring the Fulfillment of Pledges"] [Text] Northern Group of Forces—That night the tank company commanded by Captain I. Kuznetsov was to rehearse a...are commanders who reason something like this: We’ll go into the field, we can learn everything there. In particular, Capt Kuznetsov , it emerged...this. 36 But in the regiment where Capt Kuznetsov serves there are subunits which now know to achieve high results in combat training while using

  17. Integrating SIMNET into Heavy Task Force Tactical Training

    DTIC Science & Technology

    1994-10-01

    the overlays will allow the battlemaster time to input them for display on the Plan View Display ( PVD ) for use in AARs. The time schedule must also...reconnaissance for both friendly and enemy forces to occupy. The stealth station, in conjunction with the Plan View Display ( PVD ), can be used to...was moved to another assembly area for armor crewman and Nuclear, Biological, and Chemical (NBC) skills testing. The battalion observer tested 25% to

  18. EC02-0282-3

    NASA Image and Video Library

    2002-12-11

    A NASA F/A-18 flies over the Dryden Flight Research Center and Rogers Dry Lake on December 11, 2002. The aircraft participated in the Automated Aerial Refueling (AAR) project. The 300-gallon aerial refueling store seen on the belly of the aircraft carries fuel and a refueling drogue. This aircraft acted as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

  19. EC02-0282-5

    NASA Image and Video Library

    2002-12-11

    A NASA F/A-18 flies over the Dryden Flight Research Center and Rogers Dry Lake on December 11, 2002. The aircraft participated in the Automated Aerial Refueling (AAR) project. The 300-gallon aerial refueling store seen on the belly of the aircraft carries fuel and a refueling drogue. This aircraft acted as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

  20. EC02-0282-1

    NASA Image and Video Library

    2002-12-11

    A NASA F/A-18 flies over the Dryden Flight Research Center and Rogers Dry Lake on December 11, 2002. The aircraft participated in the Automated Aerial Refueling (AAR) project. The 300-gallon aerial refueling store seen on the belly of the aircraft carries fuel and a refueling drogue. This aircraft acted as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

  1. Alkali-aggregate reactivity (AAR) workshops for engineers and practitioners reference manual.

    DOT National Transportation Integrated Search

    2013-01-01

    Funding for the Federal Highway Administration (FHWA) Alkali-Silica Reactivity (ASR) Development and Deployment Program was provided under SAFETEA-LU. A related Conference Report provides additional guidance stating that project and programs related ...

  2. Glacier Changes in the Cordillera Blanca, Peru, Derived From SPOT5 Imagery, GIS and Field- Based Measurements

    NASA Astrophysics Data System (ADS)

    Racoviteanu, A.; Arnaud, Y.; Williams, M. W.; Singh Khalsa, S.

    2007-12-01

    There is urgency in deriving an extensive dataset for deriving glacier changes within the Cordillera Blanca, Peru, in a cost-effective and timely manner. Rapid glacial retreat during the last decades in this area poses a threat for water resources, hydroelectric power and local traditions. While there is some information on decadal changes in glacier extents, there still remains a paucity of mass balance measurements and glacier parameters such as hypsometry, size distribution and termini elevations. Here we investigate decadal changes in glacier parameters for Cordillera Blanca of Peru using data from Système Probatoire d'Observation de la Terre (SPOT) sensor, an old glacier inventory from 1970 aerial photography, field-based mass balance measurements and meteorological observations. Here we focus on: constructing a geospatial glacier inventory from 2003 SPOT scenes; mass balance estimations using remote sensing and field data; frequency distribution of glacier area; changes in termini elevations; hypsometry changes over time; glacier topography (slope, aspect, length/width ratio); AAR vs. mass balance for Artesonraju and Yanamarey benchmark glaciers; precipitation and temperature trends in the region. Over the last 25 years, mean temperatures increases of 0.09 deg.C/yr were greater at lower elevation than the 0.01 deg.C/yr at higher elevations, with little change in precipitation. Comparison of the new SPOT-based glacier inventory with the 1970 inventory shows that glaciers in Cordillera Blanca retreated at a rate of 0.6% per year over the last three decades, with no significant differences in the rate of area loss between E and W side. At lower elevations there is an upward shift of glacier termini along with a decrease in glacier area. Small glaciers are losing more area than large glaciers. Based on the relationship between specific mass balance (bn) and accumulation area ratio (AAR) for the two benchmark glaciers, we predicted a steady-state equilibrium line

  3. A descriptive analysis of data from the Department of Defense Joint Trauma System Prehospital Trauma Registry.

    PubMed

    Schauer, Stephen G; April, Michael D; Naylor, Jason F; Oliver, Joshua J; Cunningham, Cord W; Fisher, Andrew D; Kotwal, Russ S

    2017-01-01

    The active battlefield is an environment of chaos and confusion. Depending on the scale of combat, the chaos and confusion often extend into the prehospital combat setting with multiple personnel and units involved in the chain of care of casualties. The chaos of the prehospital combat setting has led to limitations in the availability of data for performance improvement and research. The Department of Defense (DoD) Joint Trauma System (JTS) Prehospital Trauma Registry (PHTR) was developed in conjunction with the updated Tactical Combat Casualty Care (TCCC) card and a TCCC after action report (AAR), and currently serves as the prehospital repository and module of the DoD Trauma Registry (DoDTR). We conducted a descriptive analysis of data from the DoDTR PHTR. The JTS collected trauma-associated data which comprise the PHTR are consolidated from TCCC cards and TCCC AARs. Where possible (requires 2 patient identifiers), JTS linked data from the PHTR module to other modules in the DoDTR to maximize availability of prehospital data and gain additional information regarding clinical outcomes. From January 2013 through September 2014, there were 705 patients available for research, of which 94.8% (668/705) had data from TCCC AARs, 3.3% (23/705) had data from TCCC cards, and 2.0% (14/705) had data available from DoDTR collection forms. There were one or more of the following data points per subject: pulse rate (77.4%, n=546), blood pressure (75.9%, n=535), respiratory rate (76.5%, n=539), pulse oximetry (61.8%, n=436), mental status (96.0%, n=677) and pain score (24.5%, n=173). Only 42.4% (647/1,527) of vital sign metrics had an associated time stamp. Documented interventions included limb tourniquets, of which only 27.3% (113/414) had an associated documentation of application time. Only 27.0% (190/705) of patients in the PHTR could be linked to the DoDTR due to missing identifiers. The PHTR data capture was suboptimal with many patients lacking documentation of vital

  4. Calculation and visualisation of future glacier extent in the Swiss Alps by means of hypsographic modelling

    NASA Astrophysics Data System (ADS)

    Paul, F.; Maisch, M.; Rothenbühler, C.; Hoelzle, M.; Haeberli, W.

    2007-02-01

    The observed rapid glacier wastage in the European Alps during the past 20 years already has strong impacts on the natural environment (rock fall, lake formation) as well as on human activities (tourism, hydro-power production, etc.) and poses several new challenges also for glacier monitoring. With a further increase of global mean temperature in the future, it is likely that Alpine glaciers and the high-mountain environment as an entire system will further develop into a state of imbalance. Hence, the assessment of future glacier geometries is a valuable prerequisite for various impact studies. In order to calculate and visualize in a consistent manner future glacier extent for a large number of individual glaciers (> 100) according to a given climate change scenario, we have developed an automated and simple but robust approach that is based on an empirical relationship between glacier size and the steady-state accumulation area ratio (AAR 0) in the Alps. The model requires digital glacier outlines and a digital elevation model (DEM) only and calculates new glacier geometries from a given shift of the steady-state equilibrium line altitude (ELA 0) by means of hypsographic modelling. We have calculated changes in number, area and volume for 3062 individual glacier units in Switzerland and applied six step changes in ELA 0 (from + 100 to + 600 m) combined with four different values of the AAR 0 (0.5, 0.6, 0.67, 0.75). For an AAR 0 of 0.6 and an ELA 0 rise of 200 m (400 m) we calculate a total area loss of - 54% (- 80%) and a corresponding volume loss of - 50% (- 78%) compared to the 1973 glacier extent. In combination with a geocoded satellite image, the future glacier outlines are also used for automated rendering of perspective visualisations. This is a very attractive tool for communicating research results to the general public. Our study is illustrated for a test site in the Upper Engadine (Switzerland), where landscape changes above timberline play an

  5. Effect of a hydrophilic and a hydrophobic statin on cardiac salvage after ST-elevated acute myocardial infarction - a pilot study.

    PubMed

    Chitose, Tadasuke; Sugiyama, Seigo; Sakamoto, Kenji; Shimomura, Hideki; Yamashita, Takuro; Hokamaki, Jun; Tsunoda, Ryusuke; Shiraishi, Shinya; Yamashita, Yasuyuki; Ogawa, Hisao

    2014-11-01

    Early statin therapy after acute coronary syndrome reduces atherothrombotic vascular events. This study aimed to compare the effects of hydrophilic and hydrophobic statins on myocardial salvage and left ventricular (LV) function in patients with ST-elevated myocardial infarction (STEMI). Seventy-five STEMI patients who had received emergency reperfusion therapy were enrolled and randomized into the hydrophilic statin group (rosuvastatin; 5 mg/day, n = 38) and hydrophobic statin group (atorvastatin; 10 mg/day, n = 37) for 6 months. LV ejection fraction (LVEF), and B-type natriuretic peptide (BNP) and co-enzyme Q10 (CoQ10) levels were measured at baseline and the end of treatment. The myocardial salvage index was assessed by single photon emission computed tomography with (123-)I-β-methyl-iodophenylpentadecanoic acid (ischemic area-at-risk at onset of STEMI: AAR) and (201-)thallium scintigraphy (area-at-infarction at 6 months: AAI) [myocardial salvage index = (AAR-AAI) × 100/AAR (%)]. Onset-to-balloon time and maximum creatine phosphokinase levels were comparable between the groups. After 6 months, rosuvastatin (-37.6% ± 17.2%) and atorvastatin (-32.4% ± 22.4%) equally reduced low-density lipoprotein-cholesterol (LDL-C) levels (p = 0.28). However, rosuvastatin (+3.1% ± 5.9%, p < 0.05), but not atorvastatin (+1.6% ± 5.7%, p = 0.15), improved LVEF. Rosuvastatin reduced BNP levels compared with atorvastatin (-53.3% ± 48.8% versus -13.8% ± 82.9%, p < 0.05). The myocardial salvage index was significantly higher in the rosuvastatin group than the atorvastatin group (78.6% ± 29.1% versus 52.5% ± 38.0%, p < 0.05). CoQ10/LDL-C levels at 6 months were increased in the rosuvastatin group (+23.5%, p < 0.01) and percent changes in CoQ10/LDL-C were correlated with the myocardial salvage index (r = 0.56, p < 0.01). Rosuvastatin shows better beneficial effects on myocardial salvage than atorvastatin in STEMI patients, including long-term cardiac function, associated with

  6. Role of Adenosine Receptor A2A in Traumatic Optic Neuropathies (Addendum)

    DTIC Science & Technology

    2016-03-01

    inflammation was evaluated using Western blot, Real-Time PCR and immuno-staining analyses. Role of A2AAR signaling in the anti-inflammation effect of ABT...Neuroimmunology 277 (2014) 96–104were evaluated by analysis of variance (one-way ANOVA), and the significance of differences between groups was assessed by the...Ahmad et al. / Journal of Neuroimmunology 277 (2014) 96–104were evaluated by analysis of variance (one-way ANOVA), and the significance of differences

  7. Analysis of the Exposure Levels and Potential Biologic Effects of the PAVE PAWS Radar System.

    DTIC Science & Technology

    1979-01-01

    total body) yielded local SARs at hot spots (above the palate area and the upper part of the back of the neck) about 5 times the average values for the...increase the field intensity; whether the energy absorption is averaged over the entire body or over local areas, such as the head or particularly absorptive...animal. Full implications of the multibody effects on AAR are not completely understood, even though pilot experimental studies with anesthetized rats

  8. Marine Corps Center for Lessons Learned. Volume 8, Issue 11, November 2012

    DTIC Science & Technology

    2012-11-01

    place throughout the month of July 2012 and involved 25,000 personnel from twenty-two nations and more than 40 ships and 200 aircraft. Marine Corps...from July to September 2012. Many of the principal commanders and key staff personnel who participated in the exercise were interviewed by MCCLL...01 January - 31 July 2012 (MCCLL) 2. 1st Battalion, 8th Marines (1/8) OEF 12.1 After Action Report (AAR) 3. Marine Attack Squadron 211 (VMA-211

  9. Introductory Handbook for Small Arms Ammunition

    DTIC Science & Technology

    1967-07-01

    upon a conveyor and an air jet directing the lighter scrap material into a scrap chute . As a consequence of this operation, all pieces become a...are visually inspected on a conveyor . Any scrap and all untrimmed or defective pieces are removed. g. Pocket (1) In this operation, a deep indent...are to be avoided. (3) The operation is performed on a hop- per fed, horizontal single spindle machine; I.e., a lathe design . k. Body Anneal (1

  10. Nonlinear Dynamics of Self-Pulsing All-Solid-State Lasers

    DTIC Science & Technology

    2015-07-06

    CEILAP). J.B. de La Salle 4397, (B1603ALO) Villa Martelli, Argentina 2. UBATEC Av.Roque Sáenz Peña 938 6to piso, (C1035AAR) Buenos Aires... Argentina 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) Air Force Office of Scientific Reseach 875...to get some clues to understand the complete process. The underlying hypothesis is that EE are due to the occurrence of an external crisis . In few

  11. A comparative study on improved Arrhenius-type and artificial neural network models to predict high-temperature flow behaviors in 20MnNiMo alloy.

    PubMed

    Quan, Guo-zheng; Yu, Chun-tang; Liu, Ying-ying; Xia, Yu-feng

    2014-01-01

    The stress-strain data of 20MnNiMo alloy were collected from a series of hot compressions on Gleeble-1500 thermal-mechanical simulator in the temperature range of 1173 ∼ 1473 K and strain rate range of 0.01 ∼ 10 s(-1). Based on the experimental data, the improved Arrhenius-type constitutive model and the artificial neural network (ANN) model were established to predict the high temperature flow stress of as-cast 20MnNiMo alloy. The accuracy and reliability of the improved Arrhenius-type model and the trained ANN model were further evaluated in terms of the correlation coefficient (R), the average absolute relative error (AARE), and the relative error (η). For the former, R and AARE were found to be 0.9954 and 5.26%, respectively, while, for the latter, 0.9997 and 1.02%, respectively. The relative errors (η) of the improved Arrhenius-type model and the ANN model were, respectively, in the range of -39.99% ∼ 35.05% and -3.77% ∼ 16.74%. As for the former, only 16.3% of the test data set possesses η-values within ± 1%, while, as for the latter, more than 79% possesses. The results indicate that the ANN model presents a higher predictable ability than the improved Arrhenius-type constitutive model.

  12. Functional interaction between responses to lactic acidosis and hypoxia regulates genomic transcriptional outputs

    PubMed Central

    Tang, Xiaohu; Lucas, Joseph E.; Chen, Julia Ling-Yu; LaMonte, Gregory; Wu, Jianli; Wang, Michael Changsheng; Koumenis, Constantinos; Chi, Jen-Tsan

    2011-01-01

    Within solid tumor microenvironments, lactic acidosis and hypoxia each have powerful effects on cancer pathophysiology. However, the influence that these processes exert on each other is unknown. Here we report that a significant portion of the transcriptional response to hypoxia elicited in cancer cells is abolished by simultaneous exposure to lactic acidosis. In particular, lactic acidosis abolished stabilization of HIF-1α protein which occurs normally under hypoxic conditions. In contrast, lactic acidosis strongly synergized with hypoxia to activate the unfolded protein response (UPR) and an inflammatory response, displaying a strong similarity to ATF4-driven amino acid deprivation responses (AAR). In certain breast tumors and breast tumor cells examined, an integrative analysis of gene expression and array CGH data revealed DNA copy number alterations at the ATF4 locus, an important activator of the UPR/AAR pathway. In this setting, varying ATF4 levels influenced the survival of cells after exposure to hypoxia and lactic acidosis. Our findings reveal that the condition of lactic acidosis present in solid tumors inhibits canonical hypoxia responses and activates UPR and inflammation responses. Further, they suggest that ATF4 status may be a critical determinant of the ability of cancer cells to adapt to oxygen and acidity fluctuations in the tumor microenvironment, perhaps linking short-term transcriptional responses to long-term selection for copy number alterations in cancer cells. PMID:22135092

  13. Safe use of iodinated and gadolinium-based contrast media in current practice in Japan: a questionnaire survey.

    PubMed

    Tsushima, Yoshito; Ishiguchi, Tsuneo; Murakami, Takamichi; Hayashi, Hiromitsu; Hayakawa, Katsumi; Fukuda, Kunihiko; Korogi, Yukunori; Sugimoto, Hideharu; Takehara, Yasuo; Narumi, Yoshifumi; Arai, Yasuaki; Kuwatsuru, Ryohei; Yoshimitsu, Kengo; Awai, Kazuo; Kanematsu, Masayuki; Takagi, Ryo

    2016-02-01

    To help establish consensus on the safe use of contrast media in Japan. Questionnaires were sent to accredited teaching hospitals with radiology residency programs. The reply rate was 45.4% (329/724). For contrast-induced nephropathy (CIN), chronic and acute kidney diseases were considered a risk factor in 96.7 and 93.6%, respectively, and dehydration in 73.9%. As preventive actions, intravenous hydration (89.1%) and reduction of iodinated contrast media dose (86.9%) were commonly performed. For nephrogenic systemic fibrosis (NSF), chronic and acute kidney diseases were considered risk factors in 98.5 and 90.6%, respectively, but use of unstable gadolinium-based contrast media was considered a risk factor in only 55.6%. A renal function test was always (63.5% in iodinated; 65.7% in gadolinium) or almost always (23.1; 19.8%) performed, and estimated glomerular filtration rate (eGFR) was the parameter most frequently used (80.8; 82.6%). For the patients with risk factors for acute adverse reaction (AAR), steroid premedication or/and change of contrast medium were frequent preventive actions, but intravenous steroid administration immediately before contrast media use was still performed. Our questionnaire survey revealed that preventive actions against CIN were properly performed based on patients' eGFR. Preventive actions against NSF and AAR still lacked consensus.

  14. Numerical dating of a Late Quaternary spit-shoreline complex at the northern end of Silver Lake playa, Mojave Desert, California: A comparison of the applicability of radiocarbon, luminescence, terrestrial cosmogenic nuclide, electron spin resonance, U-series and amino acid racemization methods

    USGS Publications Warehouse

    Owen, L.A.; Bright, Jordon; Finkel, R.C.; Jaiswal, M.K.; Kaufman, D.S.; Mahan, S.; Radtke, U.; Schneider, J.S.; Sharp, W.; Singhvi, A.K.; Warren, C.N.

    2007-01-01

    A Late Quaternary spit-shoreline complex on the northern shore of Pleistocene Lake Mojave of southeastern California, USA was studied with the goal of comparing accelerator mass spectrometry (AMS) radiocarbon, luminescence, electron spin resonance (ESR), terrestrial cosmogenic radionuclide (TCN) surface exposure, amino acid racemization (AAR) and U-series dating methods. The pattern of ages obtained by the different methods illustrates the complexity of processes acting in the lakeshore environment and highlights the utility of a multi-method approach. TCN surface exposure ages (mostly ???20-30 ka) record the initial erosion of shoreline benches, whereas radiocarbon ages on shells (determined in this and previous studies) within the spit, supported by AAR data, record its construction at fluctuating lake levels from ???16 to 10 ka. Luminescence ages on spit sediment (???6-7 ka) and ESR ages on spit shells (???4 ka) are anomalously young relative to radiocarbon ages of shells within the same deposits. The significance of the surprisingly young luminescence ages is not clear. The younger ESR ages could be a consequence of post-mortem enrichment of U in the shells. High concentrations of detrital thorium in tufa coating spit gravels inhibited the use of single-sample U-series dating. Detailed comparisons such as this provide one of the few means of assessing the accuracy of Quaternary dating techniques. More such comparisons are needed. ?? 2007 Elsevier Ltd and INQUA.

  15. A Modified Constitutive Model for Tensile Flow Behaviors of BR1500HS Ultra-High-Strength Steel at Medium and Low Temperature Regions

    NASA Astrophysics Data System (ADS)

    Zhao, Jun; Quan, Guo-Zheng; Pan, Jia; Wang, Xuan; Wu, Dong-Sen; Xia, Yu-Feng

    2018-01-01

    Constitutive model of materials is one of the most requisite mathematical model in the finite element analysis, which describes the relationships of flow behaviors with strain, strain rate and temperature. In order to construct such constitutive relationships of ultra-high-strength BR1500HS steel at medium and low temperature regions, the true stress-strain data over a wide temperature range of 293-873 K and strain rate range of 0.01-10 s-1 were collected from a series of isothermal uniaxial tensile tests. The experimental results show that stress-strain relationships are highly non-linear and susceptible to three parameters involving temperature, strain and strain rate. By considering the impacts of strain rate and temperature on strain hardening, a modified constitutive model based on Johnson-Cook model was proposed to characterize flow behaviors in medium and low temperature ranges. The predictability of the improved model was also evaluated by the relative error (W(%)), correlation coefficient (R) and average absolute relative error (AARE). The R-value and AARE-value for modified constitutive model at medium and low temperature regions are 0.9915 & 1.56 % and 0.9570 & 5.39 %, respectively, which indicates that the modified constitutive model can precisely estimate the flow behaviors for BR1500HS steel in the medium and low temperature regions.

  16. Gamma-glutamyl-transpeptidase to platelet ratio is not superior to APRI,FIB-4 and RPR for diagnosing liver fibrosis in CHB patients in China.

    PubMed

    Huang, Rui; Wang, Guiyang; Tian, Chen; Liu, Yong; Jia, Bei; Wang, Jian; Yang, Yue; Li, Yang; Sun, Zhenhua; Yan, Xiaomin; Xia, Juan; Xiong, Yali; Song, Peixin; Zhang, Zhaoping; Ding, Weimao; Wu, Chao

    2017-08-17

    The gamma-glutamyl transpeptidase to platelet ratio (GPR) is a novel index to estimate liver fibrosis in chronic hepatitis B (CHB). Few studies compared diagnostic accuracy of GPR with other non-invasive fibrosis tests based on blood parameters. We analyzed diagnostic values of GPR for detecting liver fibrosis and compared diagnostic performances of GPR with APRI (aspartate aminotransferase-to-platelet ratio index), FIB-4 (fibrosis index based on the four factors), NLR (neutrophil-to-lymphocyte ratio), AAR (aspartate aminotransferase/alanine aminotransferase ratio) and RPR (red cell distribution width-to-platelet ratio) in HBeAg positive CHB and HBeAg negative CHB. We found AUROCs of GPR in predicting significant liver fibrosis, advanced liver fibrosis and liver cirrhosis were 0.732 (95% CI 0.663 to 0.801), 0.788 (95% CI 0.729 to 0.847) and 0.753 (95% CI 0.692 to 0.814), respectively. Further comparisons showed the diagnostic performance of GPR was not significantly different with APRI, FIB-4 and RPR in identifying significant fibrosis, advanced fibrosis and cirrhosis, but it was significantly superior to AAR and NLR in both HBeAg positive CHB and HBeAg negative CHB. In conclusion, GPR does not show advantages than APRI, FIB-4 and RPR in identifying significant liver fibrosis, advanced liver fibrosis and liver cirrhosis in both HBeAg positive CHB and HBeAg negative CHB in China.

  17. Large-Scale Crustal-Block-Extrusion During Late Alpine Collision.

    PubMed

    Herwegh, Marco; Berger, Alfons; Baumberger, Roland; Wehrens, Philip; Kissling, Edi

    2017-03-24

    The crustal-scale geometry of the European Alps has been explained by a classical subduction-scenario comprising thrust-and-fold-related compressional wedge tectonics and isostatic rebound. However, massive blocks of crystalline basement (External Crystalline Massifs) vertically disrupt the upper-crustal wedge. In the case of the Aar massif, top basement vertically rises for >12 km and peak metamorphic temperatures increase along an orogen-perpendicular direction from 250 °C-450 °C over horizontal distances of only <15 km (Innertkirchen-Grimselpass), suggesting exhumation of midcrustal rocks with increasing uplift component along steep vertical shear zones. Here we demonstrate that delamination of European lower crust during lithosphere mantle rollback migrates northward in time. Simultaneously, the Aar massif as giant upper crustal block extrudes by buoyancy forces, while substantial volumes of lower crust accumulate underneath. Buoyancy-driven deformation generates dense networks of steep reverse faults as major structures interconnected by secondary branches with normal fault component, dissecting the entire crust up to the surface. Owing to rollback fading, the component of vertical motion reduces and is replaced by a late stage of orogenic compression as manifest by north-directed thrusting. Buoyancy-driven vertical tectonics and modest late shortening, combined with surface erosion, result in typical topographic and metamorphic gradients, which might represent general indicators for final stages of continent-continent collisions.

  18. Descriptive Epidemiology of Musculoskeletal Injuries and Concussions in the National Football League, 2012-2014

    PubMed Central

    Lawrence, David W.; Hutchison, Michael G.; Comper, Paul

    2015-01-01

    Background: The risk of all-cause injury and concussion associated with football is significant. The National Football League (NFL) has implemented changes to increase player safety warranting investigation into the incidence and patterns of injury. Purpose: To document the incidence and patterns of all-cause injury and concussions in the NFL. Study Design: Descriptive epidemiology study. Methods: Injury data were collected prospectively from official NFL injury reports over 2 regular seasons from 2012 to 2014, with identification of injury incidence rates and patterns. Concussion rate ratios were calculated using previously reported NFL rates. Results: A total of 4284 injuries were identified, including 301 concussions. The all-cause injury rate was 395.8 per 1000 athletes at risk (AAR) and concussion incidence was 27.8 per 1000 AAR. Only 2.3% of team games were injury free. Wide receivers, tight ends, and defensive backs had the highest incidence of injury and concussion. Concussion incidence was 1.61-fold higher in 2012 to 2014 compared with 2002 to 2007. The knee was injured most frequently, followed by the ankle, hamstring, shoulder, and head. Conclusion: The incidence of all-cause injury and concussion in the NFL is significant. Concussion injury rates are higher than previous reports, potentially reflecting an improvement in recognition and awareness. Injury prevention efforts should continue to reduce the prevalence of injury associated with football. PMID:26675321

  19. A Comparative Study on Improved Arrhenius-Type and Artificial Neural Network Models to Predict High-Temperature Flow Behaviors in 20MnNiMo Alloy

    PubMed Central

    Yu, Chun-tang; Liu, Ying-ying; Xia, Yu-feng

    2014-01-01

    The stress-strain data of 20MnNiMo alloy were collected from a series of hot compressions on Gleeble-1500 thermal-mechanical simulator in the temperature range of 1173∼1473 K and strain rate range of 0.01∼10 s−1. Based on the experimental data, the improved Arrhenius-type constitutive model and the artificial neural network (ANN) model were established to predict the high temperature flow stress of as-cast 20MnNiMo alloy. The accuracy and reliability of the improved Arrhenius-type model and the trained ANN model were further evaluated in terms of the correlation coefficient (R), the average absolute relative error (AARE), and the relative error (η). For the former, R and AARE were found to be 0.9954 and 5.26%, respectively, while, for the latter, 0.9997 and 1.02%, respectively. The relative errors (η) of the improved Arrhenius-type model and the ANN model were, respectively, in the range of −39.99%∼35.05% and −3.77%∼16.74%. As for the former, only 16.3% of the test data set possesses η-values within ±1%, while, as for the latter, more than 79% possesses. The results indicate that the ANN model presents a higher predictable ability than the improved Arrhenius-type constitutive model. PMID:24688358

  20. Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction.

    PubMed

    Teren, A; Kirsten, H; Beutner, F; Scholz, M; Holdt, L M; Teupser, D; Gutberlet, M; Thiery, J; Schuler, G; Eitel, I

    2017-02-03

    Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after primary angioplasty within 12 h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20 h (interquartile range: 15-25 h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarct size (IS), area at risk (AAR), myocardial salvage index (MSI) and the extent of late microvascular obstruction (lateMO). We found 398 genes associated with lateMO and two genes with IS. Neither AAR, nor MSI showed significant correlations with gene expression. Genes correlating with lateMO were strongly related to several canonical pathways, including positive regulation of T-cell activation (p = 3.44 × 10 -5 ), and regulation of inflammatory response (p = 1.86 × 10 -3 ). Network analysis of multiple gene expression alterations associated with larger lateMO identified the following functional consequences: facilitated utilisation and decreased concentration of free fatty acid, repressed cell differentiation, enhanced phagocyte movement, increased cell death, vascular disease and compensatory vasculogenesis. In conclusion, the extent of lateMO after acute, reperfused STEMI correlated with altered activation of multiple genes related to fatty acid utilisation, lymphocyte differentiation, phagocyte mobilisation, cell survival, and vascular dysfunction.

  1. The Soviet Union and the Third World. Part 2: Agenda for the 1990s

    DTIC Science & Technology

    1984-01-01

    1959, the year when Castro was in power but not yet a full-fledged Marxist-Leninist, and Felipe Pazos ran the economy. And after Costa Rica the most...of information is estimated to average 1 houj per response includig the time for revwirq Pn•[rucbi ns, aar et ng data sources a henng and maintaini...2 REPORT DATE 3 REPORT TYPE AND DATES COVERED a , Jan 84 Final: JANUARY 1984 4, TITLE AND SUBTITLE 5 FUNDING NUMBERS THE SOVIET UNION AND THE THIRD

  2. A New Program Structuring Mechanism Based on Layered Graphs.

    DTIC Science & Technology

    1984-12-01

    which is a single-page diagram. Diagrams are constructed from some 40 symbols , chiefly A- boxes, arrows and annotations. A single model specifies a...are identified and used in describing it. 20The symbol "G" derives from the original use of the term "group" for "object slice". Since Ŕ" is already an...overloaded mathematical symbol , retaining "G" seems as good as any alternative. 21The names object slices and views reflect the interpretation placed

  3. Defense Environmental Restoration Program; Annual Report to Congress for Fiscal Year 1987

    DTIC Science & Technology

    1988-03-01

    14 6 0 0 0 ARIZONA ARMY BUCKEYE 1 1 FLORENCE 1 1 FORT HUACHUCA 2 2 1 2 NAVAJO ADA 1 1 PAPAGO MILITARY RESERVATION 1 1 YUMA PROVING GROUND 2 1 1 NAVY...Aberdeen Proving Ground , MD; Jolt AAR IL; lntterken. ny AD, PA; NAS Whidbey Island, WA. All final listed or proposed sites are priority ranked "A" using...Army Ammunition Plant Doyline P MD Aberdeen Proving Ground -Michaelsville (Landfill) Aberdeen P MD Aberdeen Proving Ground -Edgewood Area Edgewood P ME

  4. USSR Report, Military Affairs, No. 1764.

    DTIC Science & Technology

    1983-04-27

    cargo in the fuse- lage can be felt in the controls—the glider is trying to raise or lower its nose and one has to parry this movement all the time...important mission to be personally involved in the defense of the country and in the accomplishment of the party’s instructions on the organization of a...are moving with our country in a single, fraternal alliance. No one can shake this great unity of like-minded people and friends for we are joined

  5. Crony Attack: Strategic Attack’s Silver Bullet

    DTIC Science & Technology

    2006-11-01

    Politics. 1. Bueno de Mesquita et al ., “Policy Failure and Political Survival,” 14–1. 1. Ibid., 149. 19. Ibid., 0. 20. Kirschner, “Microfoundations of...fighting. Notes 1. See Bueno de Mesquita et al ., “Policy Failure and Political Survival,” 147–61. 2. For more discussion of leadership’s manipulation...accessed 2 April 2003). http://www.d-i.net/fcs/;ppt/ellis_ kosovo_aar.ppt#315,7,Short War Syndrome (accessed 14 July 2006). Bueno de Mesquita, Bruce, et al

  6. An eleven-year record of mass balance of Brewster Glacier, New Zealand, determined using a geostatistical approach

    NASA Astrophysics Data System (ADS)

    Cullen, N. J.; Anderson, B.; Sirguey, P. J.; Stumm, D.; Mackintosh, A.; Conway, J. P.; Horgan, H. J.; Dadic, R.; Fitzsimons, S.; Lorrey, A.

    2016-12-01

    Recognizing the scarcity of glacier mass balance data in the Southern Hemisphere, a mass balance measurement program was started at Brewster Glacier in 2004. Evolution of the measurement regime over the 11 years of data recorded means there are differences in the spatial density of data obtained. To ensure the temporal integrity of the dataset a new, geostatistical approach has been developed to calculate mass balance. Spatial co-variance between elevation and snow depth has enabled a digital elevation model to be used in a co-kriging approach to develop a snow depth index (SDI). By capturing the observed spatial variability in snow depth, the SDI is a more reliable predictor than elevation and is used to adjust each year of measurements consistently despite variability in sampling spatial density. The SDI also resolves the spatial structure of summer balance better than elevation. Co-kriging is used again to spatially interpolate a derived mean summer balance index using SDI as a co-variate, which yields a spatial predictor for summer balance. A similar approach is also used to create a predictor for annual balance, which allows us to revisit years where summer balance was not obtained. The average glacier-wide surface winter, summer and annual mass balances over the period 2005-2015 are 2484, -2586, and -102 mm w.e., respectively, with changes in summer balance explaining most of the variability in annual balance. On the whole, there is good agreement between our ELA and AAR values and those derived from the end-of-summer snowline (EOSS) program, though discrepancies in some years cannot be fully accounted for. A mass balance map of Brewster Glacier in an equilibrium state, which by definition has a glacier-wide mass balance equal to zero (a balanced-budget), is used to calculate values of ELA (1923 ±25 m) and AAR (0.40) representative of the observational period. The relationships between mass balance and ELA/AAR are explored, demonstrating they are mostly

  7. Sensitivity of annual mass balance gradient and Hypsometry to the changing climate: the case of Dokriani Glacier, central Himalaya, India

    NASA Astrophysics Data System (ADS)

    Pratap, B.

    2015-12-01

    The glacier mass balance is undelayed, unfiltered and direct method to assess the impact of climate change on the glaciers. Many studies suggest that some of the Himalayan glaciers have lost their mass at an increased rate during the past few decades. Furthermore, the mass balance gradient and hypsometric analysis are important to understand the glacier response towards climatic perturbations. Our long term in-situ monitoring on the Dokriani Glacier provides great insights to understand the variability in central Himalayan glaciers. We report the relationship between glacier hypsometry and annual mass balance gradient (12 years) to understand the glacier's response towards climate change. Dokriani Glacier in the Bhagirathi basin is a small (7 km2) NNW exposed glacier in the western part of central Himalaya, India. The study analysed the annual balance, mass balance gradient and length changes observed during first decade of 21st century (2007-2013) and compare with the previous observations of 1990s (1992-2000). A large spatial variability in the mass balance gradients of two different periods has been observed. The equilibrium-line altitude (ELA) was fluctuated between 5000 and 5100 m a.s.l. and the derived time averaged ELA (ELAn) and balance budget ELA (ELA0) were 5075 and 4965 m a.s.l respectively during 1992-2013. The observed time-averaged accumulation-area ratio (AARn) and balance budget AAR (AAR0) were 0.67 and 0.72 respectively during 1992-2013. The higher value of AAR comprises due to flat and broader accumulation area (4.50 km2) of the glacier. Although, having larger accumulation area, the glacier has faced strong mass wasting with average annual ablation of -1.82 m w.e. a-1 in the ablation zone as compare to residual average annual accumulation of 0.41 m w.e. a-1. Based on the annual mass balance series (12 years) Dokriani Glacier has continuous negative annual balances with monotonically negative cumulative mass loss of -3.86 m w.e with the average

  8. Lung Injury Pathways: Adenosine Receptor 2B Signaling Limits Development of Ischemic Bronchiolitis Obliterans Organizing Pneumonia

    PubMed Central

    Densmore, John C.; Schaid, Terry R.; Jeziorczak, Paul M.; Medhora, Meetha; Audi, Said; Nayak, Shraddha; Auchampach, John; Dwinell, Melinda R.; Geurts, Aron M.; Jacobs, Elizabeth R.

    2018-01-01

    Purpose/Aim of the study Adenosine signaling was studied in bronchiolitis obliterans organizing pneumonia (BOOP) resulting from unilateral lung ischemia. Materials and Methods Ischemia was achieved by either left main pulmonary artery or complete hilar ligation. Sprague Dawley (SD) rats, Dahl salt sensitive (SS) rats and SS mutant rat strain containing a mutation in the A2B adenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC. A2A (A2AAR) and A2B adenosine receptor (A2BAR) mRNA and protein were quantified. Results 24h after unilateral PA ligation, BAL adenosine concentrations from ischemic lungs were increased relative to contralateral lungs in SD rats. A2BAR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. A2AAR mRNA and protein concentrations remained unchanged following ischemia. A2BAR protein was increased in PA ligated lungs of SS rats after 7d, and 4h after complete hilar ligation in SD rats. SS-Adora2b mutants showed a greater extent of BOOP relative to SS rats, and greater inflammatory changes. Conclusions Increased A2BAR and adenosine following unilateral lung ischemia as well as more BOOP in A2BAR mutant rats implicate a protective role for A2BAR signaling in countering ischemic lung injury. PMID:28266889

  9. A unified model of the standard genetic code.

    PubMed

    José, Marco V; Zamudio, Gabriel S; Morgado, Eberto R

    2017-03-01

    The Rodin-Ohno (RO) and the Delarue models divide the table of the genetic code into two classes of aminoacyl-tRNA synthetases (aaRSs I and II) with recognition from the minor or major groove sides of the tRNA acceptor stem, respectively. These models are asymmetric but they are biologically meaningful. On the other hand, the standard genetic code (SGC) can be derived from the primeval RNY code (R stands for purines, Y for pyrimidines and N any of them). In this work, the RO-model is derived by means of group actions, namely, symmetries represented by automorphisms, assuming that the SGC originated from a primeval RNY code. It turns out that the RO-model is symmetric in a six-dimensional (6D) hypercube. Conversely, using the same automorphisms, we show that the RO-model can lead to the SGC. In addition, the asymmetric Delarue model becomes symmetric by means of quotient group operations. We formulate isometric functions that convert the class aaRS I into the class aaRS II and vice versa. We show that the four polar requirement categories display a symmetrical arrangement in our 6D hypercube. Altogether these results cannot be attained, neither in two nor in three dimensions. We discuss the present unified 6D algebraic model, which is compatible with both the SGC (based upon the primeval RNY code) and the RO-model.

  10. Biochemical non-invasive assessment of liver fibrosis cannot replace biopsy in HIV-HCV coinfected patients.

    PubMed

    Kliemann, Dimas A; Wolff, Fernando H; Tovo, Cristiane V; Alencastro, Paulo R; Ikeda, Maria L R; Brandão, Ajácio B M; Barcellos, Nêmora; Fuchs, Sandra C

    2016-01-01

    The liver biopsy has been considered the gold standard for the diagnosis and quantification of fibrosis. However, this method presents limitations. In addition, the non-invasive evaluation of liver fibrosis is a challenge. The aim of this study was to validate the fibrosis cirrhosis index (FCI) index in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, and compare to AST/ALT ratio (AAR), AST to platelet ratio index (APRI) and FIB-4 scores, as a tool for the assessment of liver fibrosis in coinfected patients. Retrospective cross sectional study including 92 HIV-HCV coinfected patients evaluated in two reference centers for HIV treatment in the Public Health System in Southern Brazil. Patients who underwent liver biopsy for any indication and had concomitant laboratory data in the 3 months prior to liver biopsy, to allow the calculation of studied noninvasive markers (AAR, APRI, FIB-4 and FCI) were included. APRI < 0.5 presents the higher specificity to detect no or minimal fibrosis, whereas APRI > 1.5 presents the best negative predictive value and FCI > 1.25 the best specificity to detect significant fibrosis. The values of noninvasive markers for each Metavir fibrosis stage showed statistically significant differences only for APRI. In conclusion, until better noninvasive markers for liver fibrosis are developed and validated for HIV-HCV coinfected patients, noninvasive serum markers should be used carefully in this population.

  11. Unique relations between counterfactual thinking and DSM-5 PTSD symptom clusters.

    PubMed

    Mitchell, Melissa A; Contractor, Ateka A; Dranger, Paula; Shea, M Tracie

    2016-05-01

    Cognitive models of posttraumatic stress disorder (PTSD) propose that rumination about a trauma may increase particular symptom clusters. One type of rumination, termed counterfactual thinking (CFT), refers to thinking of alternative outcomes for an event. CFT centered on a trauma is thought to increase intrusions, negative alterations in mood and cognitions (NAMC), and marked alterations in arousal and reactivity (AAR). The theorized relations between CFT and specific symptom clusters have not been thoroughly investigated. Also, past work has not evaluated whether the relation is confounded by depressive symptoms, age, gender, or number of traumatic events experienced. The current study examined the unique associations between CFT and PTSD symptom clusters according to the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2013) in 51 trauma-exposed treatment-seeking individuals. As predicted, CFT was associated with all PTSD symptom clusters. After controlling for common predictors of PTSD symptom severity (i.e., age, depressive symptoms, and number of traumatic life events endorsed), we found CFT to be significantly associated with the intrusion and avoidance symptom clusters but not the AAR or NAMC symptom clusters. Results from the present study provide further support for the role of rumination in specific PTSD symptom clusters above and beyond symptoms of depression, age, and number of traumatic life events endorsed. Future work may consider investigating interventions to reduce rumination in PTSD. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  12. Langerhans cells beta 2-adrenoceptors: role in migration, cytokine production, Th priming and contact hypersensitivity.

    PubMed

    Maestroni, Georges J M; Mazzola, Paola

    2003-11-01

    We showed that norepinephrine (NE) hampers IL-12 and stimulates IL-10 production via adrenoceptors (ARs) in bone marrow-derived dendritic cells (BMDC) influencing their Th priming ability. Others have shown that Langerhans cells (LC) express mRNA for beta1-, beta2- and alpha1(A)-(ARs) and that catecholamines may inhibit the antigen-presenting capability via beta2-ARs. Here, we show that also BMDC express mRNA for beta1-, beta2-, alpha2(A)- and alpha2(C)-ARs. Inhibition of IL-12 is mediated by both beta2- and alpha2(A)-ARs, while stimulation of IL-10 by beta2-ARs only. In addition, LC migration, the contact hypersensitivity response (CHS) and production of IFN-gamma and IL-2 in draining lymph node cells is increased in mice treated topically with the beta2-AR antagonist ICI 118,551 during FITC sensitization. Activation of beta2-ARs in BMDC before adoptive transfer could reduce both migration and CHS response to FITC. Finally, preincubation of BMDC with LPS in presence of the specific beta2-AR agonist salbutamol impaired their chemotactic response to CCL19 and CCL21 and this effect was neutralized by anti-IL-10 mAb. We suggest that the physiological activation of beta2-ARs in DC (LC) results in stimulation of IL-10 which in turn restrains DC (LC) migration influencing antigen presentation and the consequent CHS response.

  13. 3D automatic anatomy recognition based on iterative graph-cut-ASM

    NASA Astrophysics Data System (ADS)

    Chen, Xinjian; Udupa, Jayaram K.; Bagci, Ulas; Alavi, Abass; Torigian, Drew A.

    2010-02-01

    We call the computerized assistive process of recognizing, delineating, and quantifying organs and tissue regions in medical imaging, occurring automatically during clinical image interpretation, automatic anatomy recognition (AAR). The AAR system we are developing includes five main parts: model building, object recognition, object delineation, pathology detection, and organ system quantification. In this paper, we focus on the delineation part. For the modeling part, we employ the active shape model (ASM) strategy. For recognition and delineation, we integrate several hybrid strategies of combining purely image based methods with ASM. In this paper, an iterative Graph-Cut ASM (IGCASM) method is proposed for object delineation. An algorithm called GC-ASM was presented at this symposium last year for object delineation in 2D images which attempted to combine synergistically ASM and GC. Here, we extend this method to 3D medical image delineation. The IGCASM method effectively combines the rich statistical shape information embodied in ASM with the globally optimal delineation capability of the GC method. We propose a new GC cost function, which effectively integrates the specific image information with the ASM shape model information. The proposed methods are tested on a clinical abdominal CT data set. The preliminary results show that: (a) it is feasible to explicitly bring prior 3D statistical shape information into the GC framework; (b) the 3D IGCASM delineation method improves on ASM and GC and can provide practical operational time on clinical images.

  14. Mechanisms Underlying Activation of α₁-Adrenergic Receptor-Induced Trafficking of AQP5 in Rat Parotid Acinar Cells under Isotonic or Hypotonic Conditions.

    PubMed

    Bragiel, Aneta M; Wang, Di; Pieczonka, Tomasz D; Shono, Masayuki; Ishikawa, Yasuko

    2016-06-28

    Defective cellular trafficking of aquaporin-5 (AQP5) to the apical plasma membrane (APM) in salivary glands is associated with the loss of salivary fluid secretion. To examine mechanisms of α₁-adrenoceptor (AR)-induced trafficking of AQP5, immunoconfocal microscopy and Western blot analysis were used to analyze AQP5 localization in parotid tissues stimulated with phenylephrine under different osmolality. Phenylephrine-induced trafficking of AQP5 to the APM and lateral plasma membrane (LPM) was mediated via the α1A-AR subtype, but not the α1B- and α1D-AR subtypes. Phenylephrine-induced trafficking of AQP5 was inhibited by ODQ and KT5823, inhibitors of nitric oxide (NO)-stimulated guanylcyclase (GC) and protein kinase (PK) G, respectively, indicating the involvement of the NO/ soluble (c) GC/PKG signaling pathway. Under isotonic conditions, phenylephrine-induced trafficking was inhibited by La(3+), implying the participation of store-operated Ca(2+) channel. Under hypotonic conditions, phenylephrine-induced trafficking of AQP5 to the APM was higher than that under isotonic conditions. Under non-stimulated conditions, hypotonicity-induced trafficking of AQP5 to the APM was inhibited by ruthenium red and La(3+), suggesting the involvement of extracellular Ca(2+) entry. Thus, α1A-AR activation induced the trafficking of AQP5 to the APM and LPM via the Ca(2+)/ cyclic guanosine monophosphate (cGMP)/PKG signaling pathway, which is associated with store-operated Ca(2+) entry.

  15. Winter Severe Weather: A Case Study of the Intense Squall Line of 6-7 January 1995 in the Carolinas

    DTIC Science & Technology

    1996-01-01

    line. 51 U- U- )C nM-,L Cz2r r Zr’.r - -52 cz bi2 0z CPIu Inu leu bts 533 rMPF DWPF 39 36- 30------- - - - - - - - - - - - - PMiL 014- Gusr DARR 10- 6...14u cz lo0 Go0 Go a- Nr, lou 58 ,t, 7!Ch 59 Lr, CC 7 ~ cr cz 60 z u-, II Zn zc z 11 L1X - CL Aar- c- 61 100 CCu ac- Go 62 mm IflIN Z N _ m 63 TMPF DWPF

  16. Amelie: A Recombinant Computing Framework for Ambient Awareness

    NASA Astrophysics Data System (ADS)

    Metaxas, Georgios; Markopoulos, Panos; Aarts, Emile

    This paper presents Amelie, a service oriented framework that supports the implementation of awareness systems. Amelie adopts the tenets of Recombinant computing to address an important non-functional requirement for Ambient Intelligence software, namely the heterogeneous combination of services and components. Amelie is founded upon FN-AAR an abstract model of Awareness Systems which enables the immediate expression and implementation of socially salient requirements, such as symmetry and social translucence. We discuss the framework and show how system behaviours can be specified using the Awareness Mark-up Language AML.

  17. Preliminary Assessment/Site Investigation: Tooele Army Depot, Utah. Volume 1. North Area and Facilities at Hill Air Force Base. Appendixes

    DTIC Science & Technology

    1988-12-01

    the number of 2) Facilities occunied b, Army activities other than DA forms are prohibited without copies requested in Blocks 356 of the sub-e o e...scriber’s DA Form 12-QA-R. AR 420-76as tenants when reai property control is pr i o r approv al from HQDA distrbution is C for Active Army. ARNG. uner...quality 9 3-5 Records and reporting requirements (RCS Chief of Engineers * 2-1 Nonapproprnated fund activities * 3-6 DD-M (A&AR) 1080) • 4-4 Major Army

  18. Evaluation of Various Navigation System Concepts

    DTIC Science & Technology

    1982-03-01

    Naigatimon aar01 N DAutomatic x xx Parallel 0fn x x x x x’ "OLeg t dung. n Mrankuhld M ni raia x N x to~g TAN is I OmuI,2 2mN 0 x "to - - -x...and must permit design of indicators and controls which can be directly interpreted or operated by the pilot at his normal station aboard the...the responsibility of control. The organization that controls the system can theoretically limit access to the system. Because VOVO/DME, Loran-C, and

  19. EC03-0293-03

    NASA Image and Video Library

    2003-09-18

    NASA Dryden's Automated Aerial Refueling (AAR) project evaluated the capability of an F/A-18A aircraft as an in-flight refueling tanker with the objective of developing analytical models for an automated aerial refueling system for unmanned air vehicles. The F/A-18 "tanker" aircraft (No. 847) underwent flight test envelope expansion with an aerodynamic pod containing air-refueling equipment carried beneath the fuselage. The second aircraft flew as the receiver aircraft during the study to assess the free-stream hose and drogue dynamics on the F/A-18A.

  20. EC02-0294-2

    NASA Image and Video Library

    2002-12-19

    NASA Dryden's Automated Aerial Refueling (AAR) project evaluated the capability of an F/A-18A aircraft as an in-flight refueling tanker with the objective of developing analytical models for an automated aerial refueling system for unmanned air vehicles. The F/A-18 "tanker" aircraft (No. 847) underwent flight test envelope expansion with an aerodynamic pod containing air-refueling equipment carried beneath the fuselage. The second aircraft (No. 843) flew as the receiver aircraft during the study to assess the free-stream hose and drogue dynamics on the F/A-18A.

  1. EC03-0293-15

    NASA Image and Video Library

    2003-09-18

    NASA Dryden's Automated Aerial Refueling (AAR) project evaluated the capability of an F/A-18A aircraft as an in-flight refueling tanker with the objective of developing analytical models for an automated aerial refueling system for unmanned air vehicles. The F/A-18 "tanker" aircraft (No. 847) underwent flight test envelope expansion with an aerodynamic pod containing air-refueling equipment carried beneath the fuselage. The second aircraft flew as the receiver aircraft during the study to assess the free-stream hose and drogue dynamics on the F/A-18A.

  2. EC02-0294-4

    NASA Image and Video Library

    2002-12-19

    NASA Dryden's Automated Aerial Refueling (AAR) project evaluated the capability of an F/A-18A aircraft as an in-flight refueling tanker with the objective of developing analytical models for an automated aerial refueling system for unmanned air vehicles. The F/A-18 "tanker" aircraft (No. 847) underwent flight test envelope expansion with an aerodynamic pod containing air-refueling equipment carried beneath the fuselage. The second aircraft (No. 843) flew as the receiver aircraft during the study to assess the free-stream hose and drogue dynamics on the F/A-18A.

  3. EC03-0293-06

    NASA Image and Video Library

    2003-09-18

    NASA Dryden's Automated Aerial Refueling (AAR) project evaluated the capability of an F/A-18A aircraft as an in-flight refueling tanker with the objective of developing analytical models for an automated aerial refueling system for unmanned air vehicles. The F/A-18 "tanker" aircraft (No. 847) underwent flight test envelope expansion with an aerodynamic pod containing air-refueling equipment carried beneath the fuselage. The second aircraft flew as the receiver aircraft during the study to assess the free-stream hose and drogue dynamics on the F/A-18A.

  4. EC02-0294-1

    NASA Image and Video Library

    2002-12-19

    NASA Dryden's Automated Aerial Refueling (AAR) project evaluated the capability of an F/A-18A aircraft as an in-flight refueling tanker with the objective of developing analytical models for an automated aerial refueling system for unmanned air vehicles. The F/A-18 "tanker" aircraft (No. 847) underwent flight test envelope expansion with an aerodynamic pod containing air-refueling equipment carried beneath the fuselage. The second aircraft (No. 843) flew as the receiver aircraft during the study to assess the free-stream hose and drogue dynamics on the F/A-18A.

  5. Summary of the Hungarian Provincial Press (125th of the Series)

    DTIC Science & Technology

    1960-06-24

    Party members-in the factory and oceraing tö Kr» total BEMSStt. sectary of the Plant KSZMP organziaUon, In ever r.hop in ^ition to the foreman end...turing plant there» while to Kaor.mir Hungary will send water works equifmnat« To Iraq Hungary exports textiles and other light industry products tmfi a...are still with us aM *r® must not igner« thess»* Efeoae’Who took the Party course» contributed tc the MSZMP propaganda en their r*spastiv© 5©ps and

  6. Sedimentary records of trace elements from large European lakes (Switzerland) document historic to recent freshwater pollution and climate-induced runoff variations

    NASA Astrophysics Data System (ADS)

    Thevenon, F.; Wirth, S. B.; Fujak, M.; Poté, J.; Thierry, A.; Chiaradia, M.; Girardclos, S.

    2011-12-01

    Continuous sedimentary records of anthropogenic and natural trace elements determined by ICPMS, from 5 large and deep perialpine lakes from Central Europe (Switzerland), evidence the environmental impacts of industrial fossil fuel pollution. In fact, the greatest increase in heavy metal pollution was registered at all the studied sites following the European industrial revolution of ca. AD 1800; with the highest values during the middle part of the 20th century. On a regional scale, anthropogenic heavy metal input subsequently stopped increasing thanks to remediation strategies such as the implementation of wastewater treatment plants (WWTPs). On the other hand, the discharge of industrial treated wastewaters into Vidy Bay of Lake Geneva during the second part of the 20th century involved the sedimentation of highly contaminated sediments in the area surrounding the WWTP outlet pipe discharge; less than 4 km from the main supply of drinking water of Lausanne (127'000 hab.). Microbial analyses furthermore reveal i) high increase in bacterial densities following the lake eutrophication in the 1970s, and that ii) the related sediments can be considered as a reservoir of antibiotic resistant bacteria/genes (of human origin). We finally compare instrumental hydrological data over the last century with variations of lithogenic trace elements (e.g., titanium) as registered in three large lakes (Brienz, Thun and Bienne) connected by the River Aar. This task allows to better constraining the runoff variations on a regional scale over the last decades for the the River Aar, and its possible increase under warming climate conditions in the European Alps.

  7. [Looking back but facing ahead: implementing lessons learned from the 2nd Lebanon War].

    PubMed

    Adini, Bruria; Laor, Danny; Lev, Boaz; Israeli, Avi

    2010-07-01

    The medical system utilizes a structured culture for learning lessons in order to improve the supply of services. Various tools are utilized to evaluate performance. The aim of the article is to describe the processes for learning lessons which were carried out following the Second Lebanon War and the major lessons that were identified and implemented. Three processes were performed: a process of learning Lessons of the heaLthcare system, initiated and led by the Supreme HeaLth Authority (SHA); After action review (AAR), initiated and led by the military Medical Corps and; at a later stage, a critique, initiated and led by the State Comptroller, that examined the performance of the medical system, as part of a critique on the preparedness of the home front. The following elements were defined as highly prioritized for improvement to elevate the preparedness for a future war: (1) deployment of unified clinics in conflict areas; (2) supply of medical services to the population in shelters; (3) deploying emergency medicine services, including the relationship between the Ministry of Health (MOH) and the Home Front Command (HFC); (4) defining the relationships between the MOH and HFC in deploying the community health services in emergencies; (5) protecting medical facilities and personal protection equipment for medical teams and; (6) treating acute stress reactions. The AAR, critique and learning lessons signify three different processes that can sometimes be contradictory. Nevertheless, it is possible to achieve organizational improvement white integrating between these three processes, as was displayed by the SHA.

  8. Seemingly irrational driving behavior model: The effect of habit strength and anticipated affective reactions.

    PubMed

    Chung, Yi-Shih

    2015-09-01

    An increasing amount of evidence suggests that aberrant driving behaviors are not entirely rational. On the basis of the dual-process theory, this study postulates that drivers may learn to perform irrational aberrant driving behaviors, and these behaviors could be derived either from a deliberate or an intuitive decision-making approach. Accordingly, a seemingly irrational driving behavior model is proposed; in this model, the theory of planned behavior (TPB) was adopted to represent the deliberate decision-making mechanism, and habit strength was incorporated to reflect the intuitive decision process. A multiple trivariate mediation structure was designed to reflect the process through which driving behaviors are learned. Anticipated affective reactions (AARs) were further included to examine the effect of affect on aberrant driving behaviors. Considering the example of speeding behaviors, this study developed scales and conducted a two-wave survey of students in two departments at a university in Northern Taiwan. The analysis results show that habit strength consists of multiple aspects, and frequency of past behavior cannot be a complete repository for accumulating habit strength. Habit strength appeared to be a crucial mediator between intention antecedents (e.g., attitude) and the intention itself. Including habit strength in the TPB model enhanced the explained variance of speeding intention by 26.7%. In addition, AARs were different from attitudes; particularly, young drivers tended to perform speeding behaviors to reduce negative feelings such as regret. The proposed model provides an effective alternative approach for investigating aberrant driving behaviors; corresponding countermeasures are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. A Transform-Based Feature Extraction Approach for Motor Imagery Tasks Classification

    PubMed Central

    Khorshidtalab, Aida; Mesbah, Mostefa; Salami, Momoh J. E.

    2015-01-01

    In this paper, we present a new motor imagery classification method in the context of electroencephalography (EEG)-based brain–computer interface (BCI). This method uses a signal-dependent orthogonal transform, referred to as linear prediction singular value decomposition (LP-SVD), for feature extraction. The transform defines the mapping as the left singular vectors of the LP coefficient filter impulse response matrix. Using a logistic tree-based model classifier; the extracted features are classified into one of four motor imagery movements. The proposed approach was first benchmarked against two related state-of-the-art feature extraction approaches, namely, discrete cosine transform (DCT) and adaptive autoregressive (AAR)-based methods. By achieving an accuracy of 67.35%, the LP-SVD approach outperformed the other approaches by large margins (25% compared with DCT and 6 % compared with AAR-based methods). To further improve the discriminatory capability of the extracted features and reduce the computational complexity, we enlarged the extracted feature subset by incorporating two extra features, namely, Q- and the Hotelling’s \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$T^{2}$ \\end{document} statistics of the transformed EEG and introduced a new EEG channel selection method. The performance of the EEG classification based on the expanded feature set and channel selection method was compared with that of a number of the state-of-the-art classification methods previously reported with the BCI IIIa competition data set. Our method came second with an average accuracy of 81.38%. PMID:27170898

  10. Yeast mitochondrial threonyl-tRNA synthetase recognizes tRNA isoacceptors by distinct mechanisms and promotes CUN codon reassignment

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

    Ling, Jiqiang; Peterson, Kaitlyn M.; Simonovic, Ivana

    2014-03-12

    Aminoacyl-tRNA synthetases (aaRSs) ensure faithful translation of mRNA into protein by coupling an amino acid to a set of tRNAs with conserved anticodon sequences. Here, we show that in mitochondria of Saccharomyces cerevisiae, a single aaRS (MST1) recognizes and aminoacylates two natural tRNAs that contain anticodon loops of different size and sequence. Besides a regular ?? with a threonine (Thr) anticodon, MST1 also recognizes an unusual ??, which contains an enlarged anticodon loop and an anticodon triplet that reassigns the CUN codons from leucine to threonine. Our data show that MST1 recognizes the anticodon loop in both tRNAs, but employsmore » distinct recognition mechanisms. The size but not the sequence of the anticodon loop is critical for ?? recognition, whereas the anticodon sequence is essential for aminoacylation of ??. The crystal structure of MST1 reveals that, while lacking the N-terminal editing domain, the enzyme closely resembles the bacterial threonyl-tRNA synthetase (ThrRS). A detailed structural comparison with Escherichia coli ThrRS, which is unable to aminoacylate ??, reveals differences in the anticodon-binding domain that probably allow recognition of the distinct anticodon loops. Finally, our mutational and modeling analyses identify the structural elements in MST1 (e.g., helix {alpha}11) that define tRNA selectivity. Thus, MTS1 exemplifies that a single aaRS can recognize completely divergent anticodon loops of natural isoacceptor tRNAs and that in doing so it facilitates the reassignment of the genetic code in yeast mitochondria.« less

  11. Adding intelligent services to an object oriented system

    NASA Technical Reports Server (NTRS)

    Robideaux, Bret R.; Metzler, Theodore A.

    1994-01-01

    As today's software becomes increasingly complex, the need grows for intelligence of one sort or another to becomes part of the application, often an intelligence that does not readily fit the paradigm of one's software development. There are many methods of developing software, but at this time, the most promising is the object oriented (OO) method. This method involves an analysis to abstract the problem into separate 'objects' that are unique in the data that describe them and the behavior that they exhibit, and eventually to convert this analysis into computer code using a programming language that was designed (or retrofitted) for OO implementation. This paper discusses the creation of three different applications that are analyzed, designed, and programmed using the Shlaer/Mellor method of OO development and C++ as the programming language. All three, however, require the use of an expert system to provide an intelligence that C++ (or any other 'traditional' language) is not directly suited to supply. The flexibility of CLIPS permitted us to make modifications to it that allow seamless integration with any of our applications that require an expert system. We illustrate this integration with the following applications: (1) an after action review (AAR) station that assists a reviewer in watching a simulated tank battle and developing an AAR to critique the performance of the participants in the battle; (2) an embedded training system and over-the-shoulder coach for howitzer crewmen; and (3) a system to identify various chemical compounds from their infrared absorption spectra.

  12. Implementation of a new 'community' laboratory CD4 service in a rural health district in South Africa extends laboratory services and substantially improves local reporting turnaround time.

    PubMed

    Coetzee, L M; Cassim, N; Glencross, D K

    2015-12-16

    The CD4 integrated service delivery model (ITSDM) provides for reasonable access to pathology services across South Africa (SA) by offering three new service tiers that extend services into remote, under-serviced areas. ITSDM identified Pixley ka Seme as such an under-serviced district. To address the poor service delivery in this area, a new ITSDM community (tier 3) laboratory was established in De Aar, SA. Laboratory performance and turnaround time (TAT) were monitored post implementation to assess the impact on local service delivery. Using the National Health Laboratory Service Corporate Data Warehouse, CD4 data were extracted for the period April 2012-July 2013 (n=11,964). Total mean TAT (in hours) was calculated and pre-analytical and analytical components assessed. Ongoing testing volumes, as well as external quality assessment performance across ten trials, were used to indicate post-implementation success. Data were analysed using Stata 12. Prior to the implementation of CD4 testing at De Aar, the total mean TAT was 20.5 hours. This fell to 8.2 hours post implementation, predominantly as a result of a lower pre-analytical mean TAT reducing from a mean of 18.9 to 1.8 hours. The analytical testing TAT remained unchanged after implementation and monthly test volumes increased by up to 20%. External quality assessment indicated adequate performance. Although subjective, questionnaires sent to facilities reported improved service delivery. Establishing CD4 testing in a remote community laboratory substantially reduces overall TAT. Additional community CD4 laboratories should be established in under-serviced areas, especially where laboratory infrastructure is already in place.

  13. The presence of codon-anticodon pairs in the acceptor stem of tRNAs.

    PubMed Central

    Rodin, S; Rodin, A; Ohno, S

    1996-01-01

    A total of 1268 available (excluding mitochondrial) tRNA sequences was used to reconstruct the common consensus image of their acceptor domains. Its structure appeared as a 11-bp-long double-stranded palindrome with complementary triplets in the center, each flanked by the 3'-ACCD and NGGU-5' motifs on each strand (D, base determinator). The palindrome readily extends up to the modern tRNA-like cloverleaf passing through an intermediate hairpin having in the center the single-stranded triplet, in supplement to its double-stranded precursor. The latter might represent an original anticodon-codon pair mapped at 1-2-3 positions of the present-day tRNA acceptors. This conclusion is supported by the striking correlation: in pairs of consensus tRNAs with complementary anticodons, their bases at the 2nd position of the acceptor stem were also complementary. Accordingly, inverse complementarity was also evident at the 71st position of the acceptor stem. With a single exception (tRNA(Phe)-tRNA(Glu) pair), the parallelism is especially impressive for the pairs of tRNAs recognized by aminoacyl-tRNA synthetases (aaRS) from the opposite classes. The above complementarity still doubly presented at the key central position of real single-stranded anticodons and their hypothetical double-stranded precursors is consistent with our previous data pointing to the double-strand use of ancient RNAs in the origin of the main actors in translation- tRNAs with complementary anticodons and the two classes of aaRS. Images Fig. 3 Table 2 Fig. 4 PMID:8643439

  14. Hot Deformation Behavior and Flow Stress Prediction of TC4-DT Alloy in Single-Phase Region and Dual-Phase Regions

    NASA Astrophysics Data System (ADS)

    Liu, Jianglin; Zeng, Weidong; Zhu, Yanchun; Yu, Hanqing; Zhao, Yongqing

    2015-05-01

    Isothermal compression tests of TC4-DT titanium alloy at the deformation temperature ranging from 1181 to 1341 K covering α + β phase field and β-phase field, the strain rate ranging from 0.01 to 10.0 s-1 and the height reduction of 70% were conducted on a Gleeble-3500 thermo-mechanical simulator. The experimental true stress-true strain data were employed to develop the strain-compensated Arrhenius-type flow stress model and artificial neural network (ANN) model; the predictability of two models was quantified in terms of correlation coefficient ( R) and average absolute relative error (AARE). The R and AARE for the Arrhenius-type flow stress model were 0.9952 and 5.78%, which were poorer linear relation and more deviation than 0.9997 and 1.04% for the feed-forward back-propagation ANN model, respectively. The results indicated that the trained ANN model was more efficient and accurate in predicting the flow behavior for TC4-DT titanium alloy at elevated temperature deformation than the strain-compensated Arrhenius-type constitutive equations. The constitutive relationship compensating strain could track the experimental data across the whole hot working domain other than that at high strain rates (≥1 s-1). The microstructure analysis illustrated that the deformation mechanisms existed at low strain rates (≤0.1 s-1), where dynamic recrystallization occurred, were far different from that at high strain rates (≥1 s-1) that presented bands of flow localization and cracking along grain boundary.

  15. Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid.

    PubMed

    Song, Youngzee; Zhou, Huihao; Vo, My-Nuong; Shi, Yi; Nawaz, Mir Hussain; Vargas-Rodriguez, Oscar; Diedrich, Jolene K; Yates, John R; Kishi, Shuji; Musier-Forsyth, Karin; Schimmel, Paul

    2017-12-22

    Hundreds of non-proteinogenic (np) amino acids (AA) are found in plants and can in principle enter human protein synthesis through foods. While aminoacyl-tRNA synthetase (AARS) editing potentially provides a mechanism to reject np AAs, some have pathological associations. Co-crystal structures show that vegetable-sourced azetidine-2-carboxylic acid (Aze), a dual mimic of proline and alanine, is activated by both human prolyl- and alanyl-tRNA synthetases. However, it inserts into proteins as proline, with toxic consequences in vivo. Thus, dual mimicry increases odds for mistranslation through evasion of one but not both tRNA synthetase editing systems.

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

    Richard D. Boardman; B. H. O'Brien; N. R. Soelberg

    About one million gallons of acidic, hazardous, and radioactive sodium-bearing waste are stored in stainless steel tanks at the Idaho Nuclear Technology and Engineering Center (INTEC), which is a major operating facility of the Idaho National Engineering and Environmental Laboratory. Calcination at high-temperature conditions (600 C, with alumina nitrate and calcium nitrate chemical addition to the feed) is one of four options currently being considered by the Department of Energy for treatment of the remaining tank wastes. If calcination is selected for future processing of the sodium-bearing waste, it will be necessary to install new off-gas control equipment in themore » New Waste Calcining Facility (NWCF) to comply with the Maximum Achievable Control Technology (MACT) standards for hazardous waste combustors and incinerators. This will require, as a minimum, installing a carbon bed to reduce mercury emissions from their current level of up to 7,500 to <45 {micro}g/dscm, and a staged combustor to reduce unburned kerosene fuel in the off-gas discharge to <100 ppm CO and <10 ppm hydrocarbons. The staged combustor will also reduce NOx concentrations of about 35,000 ppm by 90-95%. A pilot-plant calcination test was completed in a newly constructed 15-cm diameter calciner vessel. The pilot-plant facility was equipped with a prototype MACT off-gas control system, including a highly efficient cyclone separator and off-gas quench/venturi scrubber for particulate removal, a staged combustor for unburned hydrocarbon and NOx destruction, and a packed activated carbon bed for mercury removal and residual chloride capture. Pilot-plant testing was performed during a 50-hour system operability test January 14-16, followed by a 100-hour high-temperature calcination pilot-plant calcination run January 19-23. Two flowsheet blends were tested: a 50-hour test with an aluminum-to-alkali metal molar ratio (AAR) of 2.25, and a 50-hour test with an AAR of 1.75. Results of the testing

  17. Comparative Analysis of the Cardioprotective Properties of Opioid Receptor Agonists in a Rat Model of Myocardial Infarction

    PubMed Central

    Maslov, Leonid N.; Lishmanov, Yury B.; Oeltgen, Peter R.; Barzakh, Eva I.; Krylatov, Andrey V.; Naryzhnaya, Natalia V.; Pei, Jian-Ming; Brown, Stephen A.

    2010-01-01

    Objectives This study was conducted to test the hypothesis that opioid receptor (OR) mediated cardioprotection is agonist-specific when administered prior to coronary artery occlusion and reperfusion in a rat model. Methods Anesthetized open-chest male Wistar rats were subjected to 45 minutes of left coronary artery occlusion and 2 hours of reperfusion. Opioid agonists were infused 15 minutes prior to coronary artery occlusion. Two control groups and 15 opioid treated groups were studied. Controls were infused with either saline alone (n = 16) or dimethyl sulfoxide (DMSO) plus hydroxypropyl-β-cyclodextrin in saline (n = 19). The μ selective agonist DAMGO was infused at either 150 nmol/kg (n = 15) or 1500 nmol/kg (n = 14), and Dermorphin-H was infused at 150 nmol/kg (n = 14). The δ1 selective agonist D-Pen2,5 Enkephalin (DPDPE) was infused at 150 nmol/kg (n = 16) or 1500 nmol/kg (n = 14). The δ2 selective agonists Deltorphin II (n = 16), Deltorphin-Dvariant (n = 15) and Deltorphin-E (n = 14) were infused at 150 nmol/kg. The selective κ1 opioid agonist U-50488 was infused at 240 nmol/kg (n = 14), 1500 nmol/kg (n = 14), and 2,400 nmol/kg (n = 14). The selective κ2 opioid agonist GR-89696 was infused at 150 nmol/kg (n = 14) and 1500 nmol/kg (n = 15). Orphinan FQ (Nociceptin), also referred to as OR Ligand1 (ORL1), was infused at 220 nmol/kg (n = 15) and 1500 nmol/kg (n = 15). The infarct size/area at risk (IS/AAR) ratio was determined after reperfusion by negative staining with patent blue violet dye. Hemodynamic parameters including heart rate, mean arterial blood pressure (MAP), and rate pressure product (RPP) were determined. Results Pretreatment with the δ2 OR agonist Deltorphin II (150 nmol/kg) significantly reduced the IS/AAR ratio, while Deltorphin-Dvariant and Deltorphin-E did not exhibit an infarct sparing effect at that treatment dose. Activation of δ1 OR by DPDPE, κ1 OR by U-50488, κ2 OR by U-50488, μ OR by DAMGO, Dermophin-H, and Nociceptin had

  18. Rock Magnetic Fabrics, Paleomagnetic Vectors, and Rock Magnetic Cyclostratigraphy of the Marcellus FM, Sunbury PA

    NASA Astrophysics Data System (ADS)

    Minguez, D. A.; Kodama, K. P.

    2013-12-01

    We present the preliminary results of a multi-faceted rock magnetic study conducted on 195 samples from the Oatka Creek member of the Marcellus formation, where it has been extracted from the subsurface as a drill core near Sunbury, PA. Samples were oriented based on bedding attitude observed within the core and were removed from the core at a spacing of ≈0.25 meters starting from the base (depth ≈ 500 meters) and spanning 51 meters of stratigraphic section. The results of measurements of the anisotropy of magnetic susceptibility (AMS) consistently demonstrate a nearly triaxial fabric with maximum principal axes clustering east-west and horizontal in geographic coordinates, nearly parallel to the direction of bedding strike. AMS minimum principal axes cluster near the pole to the bedding plane. Anisotropy of anhysteretic remanence (AAR) applied with a 100 mT peak field and a 97 μT bias field in 9 orientations demonstrates a markedly different fabric, with maximum principal axis clustering north-south and horizontal in geographic coordinates. Minimum principal axes of AAR cluster steeply (~60-70 degrees) to the west. The discrepancy between AAR and AMS fabrics likely indicates the AMS is dominated by paramagnetic clays, and thus may be interpreted as an east-west intersection lineation of clay particles dipping gently north or south. Paleomagnetic directions obtained using Alternating Field (AF) demagnetization in 5 mT steps up to 110 mT demonstrates a high coercivity remanence (>35 mT) with a south and shallow direction (D= 183.4 I=-14.7). This result is consistent with previous studies of the Marcellus formation and the Devonian Catskill red beds. Thermal demagnetization experiments demonstrate a similar magnetization removed by temperatures between 250 and 350 degrees Celsius, however, continued heating results in the acquisition of strong, inconsistent magnetizations likely the result of oxidizing iron sulfides. Thermal demagnetization of orthogonal partial

  19. Hypsometric control on glacier mass balance sensitivity in Alaska

    NASA Astrophysics Data System (ADS)

    McGrath, D.; Sass, L.; Arendt, A. A.; O'Neel, S.; Kienholz, C.; Larsen, C.; Burgess, E. W.

    2015-12-01

    Mass loss from glaciers in Alaska is dominated by strongly negative surface balances, particularly on small, continental glaciers but can be highly variable from glacier to glacier. Glacier hypsometry can exert significant control on mass balance sensitivity, particularly if the equilibrium line altitude (ELA) is in a broad area of low surface slope. In this study, we explore the spatial variability in glacier response to future climate forcings on the basis of hypsometry. We first derive mass balance sensitivities (30-70 m ELA / 1° C and 40-90 m ELA / 50% decrease in snow accumulation) from the ~50-year USGS Benchmark glaciers mass balance record. We subsequently assess mean climate fields in 2090-2100 derived from the IPCC AR5/CMIP5 RCP 6.0 5-model mean. Over glaciers in Alaska, we find 2-4° C warming and 10-20% increase in precipitation relative to 2006-2015, but a corresponding 0-50% decrease in snow accumulation due to rising temperatures. We assess changes in accumulation area ratios (AAR) to a rising ELA using binned individual glacier hypsometries. For an ELA increase of 150 m, the mean statewide AAR drops by 0.45, representing a 70% reduction in accumulation area on an individual glacier basis. Small, interior glaciers are the primary drivers of this reduction and for nearly 25% of all glaciers, the new ELA exceeds the glacier's maximum elevation, portending eventual loss. The loss of small glaciers, particularly in the drier interior of Alaska will significantly modify streamflow properties (flashy hydrographs, earlier and reduced peak flows, increased interannual variability, warmer temperatures) with poorly understood downstream ecosystem and oceanographic impacts.

  20. Simultaneous Measurements of Substorm-Related Electron Energization in the Ionosphere and the Plasma Sheet

    NASA Astrophysics Data System (ADS)

    Sivadas, N.; Semeter, J.; Nishimura, Y.; Kero, A.

    2017-10-01

    On 26 March 2008, simultaneous measurements of a large substorm were made using the Poker Flat Incoherent Scatter Radar, Time History of Events and Macroscale Interactions during Substorm (THEMIS) spacecraft, and all sky cameras. After the onset, electron precipitation reached energies ≳100 keV leading to intense D region ionization. Identifying the source of energetic precipitation has been a challenge because of lack of quantitative and magnetically conjugate measurements of loss cone electrons. In this study, we use the maximum entropy inversion technique to invert altitude profiles of ionization measured by the radar to estimate the loss cone energy spectra of primary electrons. By comparing them with magnetically conjugate measurements from THEMIS-D spacecraft in the nightside plasma sheet, we constrain the source location and acceleration mechanism of precipitating electrons of different energy ranges. Our analysis suggests that the observed electrons ≳100 keV are a result of pitch angle scattering of electrons originating from or tailward of the inner plasma sheet at 9RE, possibly through interaction with electromagnetic ion cyclotron waves. The electrons of energy 10-100 keV are produced by pitch angle scattering due to a potential drop of ≲10 kV in the auroral acceleration region (AAR) as well as wave-particle interactions in and tailward of the AAR. This work demonstrates the utility of magnetically conjugate ground- and space-based measurements in constraining the source of energetic electron precipitation. Unlike in situ spacecraft measurements, ground-based incoherent scatter radars combined with an appropriate inversion technique can be used to provide remote and continuous-time estimates of loss cone electrons in the plasma sheet.

  1. The predictive value of noninvasive serum markers of liver fibrosis in patients with chronic hepatitis C.

    PubMed

    Gökcan, Hale; Kuzu, Ufuk Barış; Öztaş, Erkin; Saygılı, Fatih; Öztuna, Derya; Suna, Nuretdin; Tenlik, İlyas; Akdoğan, Meral; Kaçar, Sabite; Kılıç, Zeki Mesut Yalın; Kayaçetin, Ertuğrul

    2016-03-01

    This study aims to show the predictive value of noninvasive serum markers on the hepatic fibrosis level. This cross sectional study involves 120 patients with chronic hepatitis C. The noninvasive markers used were as follows: age-platelet index (AP index), cirrhosis discriminant score (CDS), aspartate aminotransferase (AST)-alanine aminotransferase (ALT) ratio (AAR), fibrosis-4 (FIB-4) index, AST-platelet ratio index (APRI), Goteborg University Cirrhosis Index (GUCI), FibroQ, King's score, platelet count. Concurrent liver biopsies were evaluated using the modified Ishak and Knodell scoring systems. In accordance with the Knodell scores, F3-F4 scores were defined as "severe fibrosis," and the modified Ishak scores stage of ≥3 (F3-F6) were defined as "clinically significant fibrosis." Receiver Operating Characteristic (ROC) curve analyses were carried out to compare the noninvasive markers with hepatic fibrosis level. Mean age of the patients was 51.7±11.6. A total of 10 patients (8.3%) with Knodell scores and 24 patients (20%) with modified Ishak scores were evaluated to have ≥F3 hepatic fibrosis. ROC analyses with the Knodell and modified Ishak scores were as follows: AP index=0.61-0.57, CDS=0.66-0.55, AAR=0.60-0.49, FIB-4=0.70-0.68, APRI=0.67-0.72, GUCI=0.66-0.72, FibroQ=0.64-0.54, King's score=0.68-0.54, platelet count=0.61-0.55. We found that APRI, FIB-4, King's score, and GUCI can be used to determination patients with mild fibrosis with a high negative predictive value and in the differentiation of severe/significant fibrosis from mild to moderate fibrosis.

  2. Effects of a significant New Madrid Seismic Zone event on oil and natural gas pipelines and their cascading effects to critical infrastructures

    NASA Astrophysics Data System (ADS)

    Fields, Damon E.

    Critical Infrastructure Protection (CIP) is a construct that relates preparedness and responsiveness to natural or man-made disasters that involve vulnerable assets deemed essential for the functioning of our economy and society. Infrastructure systems (power grids, bridges, airports, etc.) are vulnerable to disastrous types of events--natural or man-made. Failures of these systems can have devastating effects on communities and entire regions. CIP relates our willingness, ability, and capability to defend, mitigate, and re-constitute those assets that succumb to disasters affecting one or more infrastructure sectors. This qualitative research utilized ethnography and employed interviews with subject matter experts (SMEs) from various fields of study regarding CIP with respect to oil and natural gas pipelines in the New Madrid Seismic Zone. The study focused on the research question: What can be done to mitigate vulnerabilities in the oil and natural gas infrastructures, along with the potential cascading effects to interdependent systems, associated with a New Madrid fault event? The researcher also analyzed National Level Exercises (NLE) and real world events, and associated After Action Reports (AAR) and Lessons Learned (LL) in order to place a holistic lens across all infrastructures and their dependencies and interdependencies. Three main themes related to the research question emerged: (a) preparedness, (b) mitigation, and (c) impacts. These themes comprised several dimensions: (a) redundancy, (b) node hardening, (c) education, (d) infrastructure damage, (e) cascading effects, (f) interdependencies, (g) exercises, and (h) earthquake readiness. As themes and dimensions are analyzed, they are considered against findings in AARs and LL from previous real world events and large scale exercise events for validation or rejection.

  3. Microphysiometric analysis of human α1a-adrenoceptor expressed in Chinese hamster ovary cells

    PubMed Central

    Taniguchi, Takanobu; Inagaki, Rika; Murata, Satoshi; Akiba, Isamu; Muramatsu, Ikunobu

    1999-01-01

    The human recombinant α1a-adrenoceptor (AR) has been stably expressed in Chinese hamster ovary cells. Four stable clones, aH4, aH5, aH6 and aH7, expressing 30, 370, 940 and 2900 fmol AR mg−1 protein, respectively, have been employed to characterize this AR subtype using radioligand binding and microphysiometry to measure extracellular acidification rates.Noradrenaline (NA) gave concentration-dependent responses in microphysiometry with increasing extracellular acidification rates. The potency of NA increased as the receptor density increased; pEC50 values of NA for the clones aH4, aH5, aH6 and aH7 were 6.9, 7.5, 7.8 and 8.1, respectively. This increase of potency according to receptor density indicates the presence of spare receptor for NA. Methoxamine, phenylephrine, oxymetazoline and clonidine also gave concentration-dependent responses with various intrinsic activities.Antagonists shifted concentration-response curves for NA rightward in a concentration-dependent manner. Schild analysis revealed that the affinity profile of this AR subtype to antagonists in the clone aH7 had a typical pattern for the α1a-AR; high affinity for prazosin and WB 4101, and low affinity for BMY7378 (pA2=9.5, 9.8 and 7.3, respectively). This profile is similar in the case of the clone aH4. These affinities were in good agreement with those obtained in binding experiments.These results have demonstrated that (1) classical receptor theory can be applied in microphysiometry, and (2) microphysiometry is a useful tool to investigate the pharmacological characterization of α1a-AR. PMID:10433504

  4. Exome Sequencing Identifies Mitochondrial Alanyl-tRNA Synthetase Mutations in Infantile Mitochondrial Cardiomyopathy

    PubMed Central

    Götz, Alexandra; Tyynismaa, Henna; Euro, Liliya; Ellonen, Pekka; Hyötyläinen, Tuulia; Ojala, Tiina; Hämäläinen, Riikka H.; Tommiska, Johanna; Raivio, Taneli; Oresic, Matej; Karikoski, Riitta; Tammela, Outi; Simola, Kalle O.J.; Paetau, Anders; Tyni, Tiina; Suomalainen, Anu

    2011-01-01

    Infantile cardiomyopathies are devastating fatal disorders of the neonatal period or the first year of life. Mitochondrial dysfunction is a common cause of this group of diseases, but the underlying gene defects have been characterized in only a minority of cases, because tissue specificity of the manifestation hampers functional cloning and the heterogeneity of causative factors hinders collection of informative family materials. We sequenced the exome of a patient who died at the age of 10 months of hypertrophic mitochondrial cardiomyopathy with combined cardiac respiratory chain complex I and IV deficiency. Rigorous data analysis allowed us to identify a homozygous missense mutation in AARS2, which we showed to encode the mitochondrial alanyl-tRNA synthetase (mtAlaRS). Two siblings from another family, both of whom died perinatally of hypertrophic cardiomyopathy, had the same mutation, compound heterozygous with another missense mutation. Protein structure modeling of mtAlaRS suggested that one of the mutations affected a unique tRNA recognition site in the editing domain, leading to incorrect tRNA aminoacylation, whereas the second mutation severely disturbed the catalytic function, preventing tRNA aminoacylation. We show here that mutations in AARS2 cause perinatal or infantile cardiomyopathy with near-total combined mitochondrial respiratory chain deficiency in the heart. Our results indicate that exome sequencing is a powerful tool for identifying mutations in single patients and allows recognition of the genetic background in single-gene disorders of variable clinical manifestation and tissue-specific disease. Furthermore, we show that mitochondrial disorders extend to prenatal life and are an important cause of early infantile cardiac failure. PMID:21549344

  5. Mechanical tissue resuscitation (MTR): a nonpharmacological approach to treatment of acute myocardial infarction.

    PubMed

    Jordan, James E; Pereira, Beatriz D; Lane, Magan R; Morykwas, Michael J; McGee, Maria; Argenta, Louis C

    2015-08-01

    Myocardial ischemia-reperfusion injury is known to trigger an inflammatory response involving edema, apoptosis, and neutrophil activation/accumulation. Recently, mechanical tissue resuscitation (MTR) was described as a potent cardioprotective strategy for reduction of myocardial ischemia-reperfusion injury. Here, we further describe the protective actions of MTR and begin to define its therapeutic window. A left ventricular, free-wall ischemic area was created in anesthetized swine for 85 minutes and then reperfused for three hours. Animals were randomized to two groups: (1) untreated controls (Control) and (2) application of MTR that was delayed 90 minutes after the initiation of reperfusion (D90). Hemodynamics and regional myocardial blood flow were assessed at multiple time points. Infarct size and neutrophil accumulation were assessed following the reperfusion period. In separate cohorts, the effect of MTR on myocardial interstitial water (MRI imaging) and blood flow was examined. Both groups had similar areas at risk (AAR), hemodynamics, and arterial blood gas values. MTR, even when delayed 90 minutes into reperfusion (D90, 29.2 ± 5.0% of AAR), reduced infarct size significantly compared to Controls (51.9 ± 2.7%, p = 0.006). This protection was associated with a 33% decrease in neutrophil accumulation (p = 0.047). Improvements in blood flow and interstitial water were also observed. Moreover, we demonstrated that the therapeutic window for MTR lasts for at least 90 minutes following reperfusion. This study confirms our previous observations that MTR is an effective therapeutic approach to reducing reperfusion injury with a clinically useful treatment window. © 2015 Wiley Periodicals, Inc.

  6. Socio-environmental factors and diarrheal diseases in under five-year old children in the state of Tocantins, Brazil

    PubMed Central

    Graepp-Fontoura, Iolanda; Santos, Floriacy Stabnow; Santos Neto, Marcelino; Tavares, Hanari Santos de Almeida; Bezerra, Maria Onice Lopes; Feitosa, Marcela de Oliveira; Neves, Adriano Figuerêdo; de Morais, Jesuane Cavalcante Melo; Nascimento, Luiz Fernando Costa

    2018-01-01

    Background Diarrhea is a waterborne disease that affects children, especially those under 5 years of age. The objective of this study was to identify the spatial patterns of distribution of diarrheal disease in under 5-year-old children in the State of Tocantins, Brazil, from 2008 to 2013. Methods Geoprocessing tools were used to carry out an epidemiological study, to prepare thematic maps in the TerraView 4.2.2 software based on secondary data. General indicators of the disease, presence of spatial dependence through the Global Moran’s Index (I) and the Spatial Association Index (LISA) were described. Results There were 3,015 cases of under 5-year-old children hospitalized for diarrhea, with an average annual rate (AAR) of 4.10/1,000 inhabitants (inhab.). Among the main characteristics were: increasing rates in under 1-year-old children (6.16 to 9.66/1,000 inhabitants); children aged 1 to 4 full years (63%); males (55%); 8 deaths of under one-year-old children (75%); county of Araguaína (67%); incidence in the county of Nazaré (63.97/1,000 inhab.); prevalence and incidence in the Araguaína microregion (45%, AAR 9.38/1,000 inhab.). The presence of a cluster with spatial autocorrelation was found in the Araguaína microregion, which was statistically significant (I = 0.11, p-value < 0.03), with priority of intervention (Moran Map). Conclusions There was an increase in the number of hospitalizations for diarrhea in under 5–year-old children in the state of Tocantins. The spatial analysis identified clusters of priority areas for measures of maintenance and control of diarrheal diseases. PMID:29768428

  7. Importance to question sinonasal symptoms and to perform rhinoscopy and rhinomanometry in cystic fibrosis patients.

    PubMed

    Bock, J M; Schien, M; Fischer, C; Naehrlich, L; Kaeding, M; Guntinas-Lichius, O; Gerber, A; Arnold, C; Mainz, J G

    2017-02-01

    Cystic fibrosis (CF) patients almost regularly reveal sinonasal pathology. The purpose of this study was to assess association between objective and subjective measurements of sinonasal involvement comparing nasal airflow obtained by active anterior rhinomanometry (AAR), nasal endoscopic findings, and symptoms assessed with the Sino-Nasal Outcome Test-20 (SNOT-20). Nasal cavities were explored by anterior rigid rhinoscopy and findings were compared to inspiratory nasal airflow measured by AAR to quantify nasal patency and subjective health-related quality of life in sinonasal disease obtained with the SNOT-20 questionnaire. Relations to upper and lower airway colonization with Pseudomonas aeruginosa, medical treatment, and sinonasal surgery were analysed. A total of 124 CF patients were enrolled (mean age 19.9 ± 10.4 years, range 4-65 years). A significant association of detection of nasal polyposis (NP) in rhinoscopy was found with increased primary nasal symptoms (PNS) which include "nasal obstruction," "sneezing," "runny nose," "thick nasal discharge," and "reduced sense of smell." At the same time patients with pathologically decreased airflow neither showed elevated SNOT-20 scores nor abnormal rhinoscopic findings. Altogether, rhinomanometric and rhinoscopic findings are not significantly related. Among SNOT-20 scores the PNS subscore is related to rhinoscopically detected polyposis and sinonasal secretion. Therefore, we recommend including short questions regarding PNS into CF-routine care. At the same time our results show that a high inspiratory airflow is not associated with a good sensation of nasal patency. Altogether, rhinomanometry is not required within routine CF-care, but it can be interesting as an outcome parameter within clinical trials. Pediatr Pulmonol. 2017;52:167-174. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. The NASA Dryden AAR Project: A Flight Test Approach to an Aerial Refueling System

    NASA Technical Reports Server (NTRS)

    Hansen, Jennifer L.; Murray, James E.; Campos, Norma V.

    2004-01-01

    The integration of uninhabited aerial vehicles (UAVs) into controlled airspace has generated a new era of autonomous technologies and challenges. Autonomous aerial refueling would enable UAVs to travel further distances and loiter for extended periods over time-critical targets. The NASA Dryden Flight Research Center recently has completed a flight research project directed at developing a dynamic hose and drogue system model to support the development of an automated aerial refueling system. A systematic dynamic model of the hose and drogue system would include the effects of various influences on the system, such as flight condition, hose and drogue type, tanker type and weight, receiver type, and tanker and receiver maneuvering. Using two NASA F/A-18 aircraft and a conventional hose and drogue aerial refueling store from the Navy, NASA has obtained flight research data that document the response of the hose and drogue system to these effects. Preliminary results, salient trends, and important lessons are presented.

  9. Abdominal compartment syndrome and ruptured aortic aneurysm: Validation of a predictive test (SCA-AAR).

    PubMed

    Leclerc, Betty; Salomon Du Mont, Lucie; Parmentier, Anne-Laure; Besch, Guillaume; Rinckenbach, Simon

    2018-06-01

    The abdominal compartment syndrome (ACS) has been clearly identified as being one of the main causes of mortality after ruptured abdominal aortic aneurysm (rAAA). The ACS is defined as a sustained intra-abdominal pressure > 20 mm Hg associated with a new organ dysfunction or failure. A pilot study was conducted and found that the threshold of 3 among 8 selected criteria, we would predict an ACS occurrence with a 54% positive predictive value and a 92% negative predictive value. But a multicentric prospective study was clearly needed to confirm these results. The outcome of this new study is to assess the qualities of a predictive test on occurrence of the ACS after rAAA surgery. This is a 30 months prospective cohort study conducted in 12 centers and 165 patients will be included. All patients with a rAAA will be consecutively included, whatever the surgical treatment. At the end of surgery, all patients have an abdominal closure and a monitoring of intrabladder pressure will be established every 3 to 4 hours. Decompressive laparotomy will be indicated when ACS occurs. Follow-up period is 1 month. Eight pre- and per-operative criteria will be studied: anemia, hypotension, cardiac arrest, obesity, massive fluid resuscitation, transfusion, hypothermia, and acidosis. In the literature, there is no recommendation about prophylactic decompression, but early decompressive laparotomy appears to improve survival. This study should make it possible to establish a predictive test, detect the ACS early, and consider a prophylactic decompression in the operating room. ClinicalTrials.gov, NCT02859662, Registered on 4 August 2016.

  10. Fatigue behavior of AAR Class A railroad wheel steel at ambient and elevated temperatures.

    DOT National Transportation Integrated Search

    2006-12-01

    This report documents a test program to determine the material properties (chemical composition, tensile, and fatigue) at ambient and elevated temperatures of a Class A wheel steel as designated by the Association of American Railroads. The 3 tempera...

  11. 76 FR 47612 - AAR Manufacturing, Inc.; Completion of Radiological Survey Activities at CSX Transportation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-05

    ... Plan list in August 1994. In May 1997, NRC inspectors performed a limited radiation survey of the CSXT..., 1997, letter; the report identified three locations with elevated levels of thorium in the soil (ADAMS... CSXT property. Based on the survey and sampling results, as well as an all- pathways analysis of the...

  12. A Service for Emotion Management: Turkish Version of the Adolescent Anger Rating Scale (AARS)

    ERIC Educational Resources Information Center

    Aslan, A. Esra; Sevincler-Togan, Seyhan

    2009-01-01

    An individual's activities are closely related with his/her communication abilities. One's awareness of his feelings and needs and to what extend he can control such feelings are the key factors which effect communication abilities. Webster (1996) defines anger as, "a strong emotion; a feeling that is oriented toward some real or supposed…

  13. Fuzzylot: a novel self-organising fuzzy-neural rule-based pilot system for automated vehicles.

    PubMed

    Pasquier, M; Quek, C; Toh, M

    2001-10-01

    This paper presents part of our research work concerned with the realisation of an Intelligent Vehicle and the technologies required for its routing, navigation, and control. An automated driver prototype has been developed using a self-organising fuzzy rule-based system (POPFNN-CRI(S)) to model and subsequently emulate human driving expertise. The ability of fuzzy logic to represent vague information using linguistic variables makes it a powerful tool to develop rule-based control systems when an exact working model is not available, as is the case of any vehicle-driving task. Designing a fuzzy system, however, is a complex endeavour, due to the need to define the variables and their associated fuzzy sets, and determine a suitable rule base. Many efforts have thus been devoted to automating this process, yielding the development of learning and optimisation techniques. One of them is the family of POP-FNNs, or Pseudo-Outer Product Fuzzy Neural Networks (TVR, AARS(S), AARS(NS), CRI, Yager). These generic self-organising neural networks developed at the Intelligent Systems Laboratory (ISL/NTU) are based on formal fuzzy mathematical theory and are able to objectively extract a fuzzy rule base from training data. In this application, a driving simulator has been developed, that integrates a detailed model of the car dynamics, complete with engine characteristics and environmental parameters, and an OpenGL-based 3D-simulation interface coupled with driving wheel and accelerator/ brake pedals. The simulator has been used on various road scenarios to record from a human pilot driving data consisting of steering and speed control actions associated to road features. Specifically, the POPFNN-CRI(S) system is used to cluster the data and extract a fuzzy rule base modelling the human driving behaviour. Finally, the effectiveness of the generated rule base has been validated using the simulator in autopilot mode.

  14. An evaluation of Mesodon and other larger terrestrial gastropod shells for dating late Holocene and historic alluvium in the Midwestern USA

    USGS Publications Warehouse

    Rakovan, Monica T.; Rech, Jason A.; Pigati, Jeffery S.; Nekola, Jeffery C.; Wiles, Gregory C.

    2013-01-01

    Understanding the history of stream erosion and changes in channel morphology is important for managing and restoring unstable streams. One of the significant challenges in this type of research is establishing accurate dating of late Holocene and historic alluvium. Here we evaluate the potential of using 14C dating and amino acid racemization (AAR) to date large terrestrial gastropod shells that are often preserved within alluvial sediments. Many terrestrial gastropods incorporate old carbon from limestone or other carbonate rocks into their shells and therefore are unsuitable for radiocarbon dating. Recent studies, however, have shown that some taxa avoid this ‘limestone problem’ and can yield reliable 14C ages. In this study, we measured the 14C activity of specimens for the genera Mesodon, Ventridens, and Allogona collected live and from alluvial sequences dated independently by dendrochronology, 14C dating of wood, and/or 137Cs analyses. Mesodon zaletus contained old carbon in similar concentrations (up to ~ 30%) found in previous studies of other large taxa and should be avoided for 14C dating when possible. In contrast, shells of Ventridens ligera and Allogona profunda showed minimal limestone effects and therefore may be suitable for dating late Holocene alluvium. These results highlight the importance of taxonomic identification of gastropod taxa prior to their use for 14C dating and demonstrate that shell fragments that are not identifiable should be avoided. We also measured d/l ratios (n = 17) of aspartic and glutamic acid from eight different taxa of terrestrial gastropods recovered from four late Holocene and historic stratigraphic sequences. Average d/l ratios of aspartic and glutamic acid from historic sediments < 300 years old are lower in shells from younger stratigraphic units, indicating that AAR can be used to differentiate between multiple historic stratigraphic units.

  15. The three α1-adrenoceptor subtypes show different spatio-temporal mechanisms of internalization and ERK1/2 phosphorylation.

    PubMed

    Perez-Aso, M; Segura, V; Montó, F; Barettino, D; Noguera, M A; Milligan, G; D'Ocon, P

    2013-10-01

    We analyzed the kinetic and spatial patterns characterizing activation of the MAP kinases ERK 1 and 2 (ERK1/2) by the three α1-adrenoceptor (α1-AR) subtypes in HEK293 cells and the contribution of two different pathways to ERK1/2 phosphorylation: protein kinase C (PKC)-dependent ERK1/2 activation and internalization-dependent ERK1/2 activation. The different pathways of phenylephrine induced ERK phosphorylation were determined by western blot, using the PKC inhibitor Ro 31-8425, the receptor internalization inhibitor concanavalin A and the siRNA targeting β-arrestin 2. Receptor internalization properties were studied using CypHer5 technology and VSV-G epitope-tagged receptors. Activation of α1A- and α1B-ARs by phenylephrine elicited rapid ERK1/2 phosphorylation that was directed to the nucleus and inhibited by Ro 31-8425. Concomitant with phenylephrine induced receptor internalization α1A-AR, but not α1B-AR, produced a maintained and PKC-independent ERK phosphorylation, which was restricted to the cytosol and inhibited by β-arrestin 2 knockdown or concanavalin A treatment. α1D-AR displayed constitutive ERK phosphorylation, which was reduced by incubation with prazosin or the selective α1D antagonist BMY7378. Following activation by phenylephrine, α1D-AR elicited rapid, transient ERK1/2 phosphorylation that was restricted to the cytosol and not inhibited by Ro 31-8425. Internalization of the α1D-AR subtype was not observed via CypHer5 technology. The three α1-AR subtypes present different spatio-temporal patterns of receptor internalization, and only α1A-AR stimulation translates to a late, sustained ERK1/2 phosphorylation that is restricted to the cytosol and dependent on β-arrestin 2 mediated internalization. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Genetic variant rs3750625 in the 3′UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site

    PubMed Central

    Linnstaedt, Sarah D.; Walker, Margaret G.; Riker, Kyle D.; Nyland, Jennifer E.; Hu, JunMei; Rossi, Catherine; Swor, Robert A.; Jones, Jeffrey S.; Diatchenko, Luda; Bortsov, Andrey V.; Peak, David A.; McLean, Samuel A.

    2016-01-01

    α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs. facilitation after both physical and psychological stress. To our knowledge the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3′UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity. We evaluated rs3750625 because it is located in the seed binding region of miR-34a, a microRNA (miRNA) known to regulate pain and stress responses. In both cohorts, the minor allele at rs3750625 was associated with increased MSP in distressed individuals (stress*rs3750625 p = 0.043 for MVC cohort and p = 0.007 for sexual assault cohort). We further found that (1) miR-34a binds the 3′UTR of ADRA2A, (2) the amount of repression is greater when the minor (risk) allele is present, (3) miR-34a in the IMR-32 adrenergic neuroblastoma cell line affects ADRA2A expression, (4) miR-34a and ADRA2A are expressed in tissues known to play a role in pain and stress, (5) following forced swim stress exposure, rat peripheral nerve tissue expression changes are consistent with miR-34a regulation of ADRA2A. Together these results suggest that ADRA2A rs3750625 contributes to post-stress MSP severity by modulating miR-34a regulation. PMID:27805929

  17. Genetic variant rs3750625 in the 3'UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site.

    PubMed

    Linnstaedt, Sarah D; Walker, Margaret G; Riker, Kyle D; Nyland, Jennifer E; Hu, JunMei; Rossi, Catherine; Swor, Robert A; Jones, Jeffrey S; Diatchenko, Luda; Bortsov, Andrey V; Peak, David A; McLean, Samuel A

    2017-02-01

    α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs facilitation after both physical and psychological stress. To our knowledge, the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3'UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity. We evaluated rs3750625 because it is located in the seed binding region of miR-34a, a microRNA (miRNA) known to regulate pain and stress responses. In both cohorts, the minor allele at rs3750625 was associated with increased musculoskeletal pain in distressed individuals (stress*rs3750625 P = 0.043 for MVC cohort and P = 0.007 for sexual assault cohort). We further found that (1) miR-34a binds the 3'UTR of ADRA2A, (2) the amount of repression is greater when the minor (risk) allele is present, (3) miR-34a in the IMR-32 adrenergic neuroblastoma cell line affects ADRA2A expression, (4) miR-34a and ADRA2A are expressed in tissues known to play a role in pain and stress, (5) following forced swim stress exposure, rat peripheral nerve tissue expression changes are consistent with miR-34a regulation of ADRA2A. Together, these results suggest that ADRA2A rs3750625 contributes to poststress musculoskeletal pain severity by modulating miR-34a regulation.

  18. Fat segmentation on chest CT images via fuzzy models

    NASA Astrophysics Data System (ADS)

    Tong, Yubing; Udupa, Jayaram K.; Wu, Caiyun; Pednekar, Gargi; Subramanian, Janani Rajan; Lederer, David J.; Christie, Jason; Torigian, Drew A.

    2016-03-01

    Quantification of fat throughout the body is vital for the study of many diseases. In the thorax, it is important for lung transplant candidates since obesity and being underweight are contraindications to lung transplantation given their associations with increased mortality. Common approaches for thoracic fat segmentation are all interactive in nature, requiring significant manual effort to draw the interfaces between fat and muscle with low efficiency and questionable repeatability. The goal of this paper is to explore a practical way for the segmentation of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) components of chest fat based on a recently developed body-wide automatic anatomy recognition (AAR) methodology. The AAR approach involves 3 main steps: building a fuzzy anatomy model of the body region involving all its major representative objects, recognizing objects in any given test image, and delineating the objects. We made several modifications to these steps to develop an effective solution to delineate SAT/VAT components of fat. Two new objects representing interfaces of SAT and VAT regions with other tissues, SatIn and VatIn are defined, rather than using directly the SAT and VAT components as objects for constructing the models. A hierarchical arrangement of these new and other reference objects is built to facilitate their recognition in the hierarchical order. Subsequently, accurate delineations of the SAT/VAT components are derived from these objects. Unenhanced CT images from 40 lung transplant candidates were utilized in experimentally evaluating this new strategy. Mean object location error achieved was about 2 voxels and delineation error in terms of false positive and false negative volume fractions were, respectively, 0.07 and 0.1 for SAT and 0.04 and 0.2 for VAT.

  19. Structure of Leishmania major Methionyl-tRNA Synthetase in Complex with Intermediate Products Methionyladenylate and Pyrophosphate

    PubMed Central

    Larson, Eric T.; Kim, Jessica E.; Zucker, Frank H.; Kelley, Angela; Mueller, Natascha; Napuli, Alberto J.; Verlinde, Christophe L.M.J.; Fan, Erkang; Buckner, Frederick S.; Van Voorhis, Wesley C.; Merritt, Ethan A.; Hol, Wim G.J.

    2011-01-01

    Leishmania parasites cause two million new cases of leishmaniasis each year with several hundreds of millions people at risk. Due to the paucity and shortcomings of available drugs, we have undertaken the crystal structure determination of a key enzyme from Leishmania major in hopes of creating a platform for the rational design of new therapeutics. Crystals of the catalytic core of methionyl-tRNA synthetase from L. major (LmMetRS) were obtained with the substrates MgATP and methionine present in the crystallization medium. These crystals yielded the 2.0 Å resolution structure of LmMetRS in complex with two products, methionyladenylate and pyrophosphate, along with a Mg2+ ion that bridges them. This is the first class I aminoacyl-tRNA synthetase (aaRS) structure with pyrophosphate bound. The residues of the class I aaRS signature sequence motifs, KISKS and HIGH, make numerous contacts with the pyrophosphate. Substantial differences between the LmMetRS structure and previously reported complexes of E. coli MetRS (EcMetRS) with analogs of the methionyladenylate intermediate product are observed, even though one of these analogs only differs by one atom from the intermediate. The source of these structural differences is attributed to the presence of the product pyrophosphate in LmMetRS. Analysis of the LmMetRS structure in light of the Aquifex aeolicus MetRS-tRNAMet complex shows that major rearrangements of multiple structural elements of enzyme and/or tRNA are required to allow the CCA acceptor triplet to reach the methionyladenylate intermediate in the active site. Comparison with sequences of human cytosolic and mitochondrial MetRS reveals interesting differences near the ATP- and methionine-binding regions of LmMetRS, suggesting that it should be possible to obtain compounds that selectively inhibit the parasite enzyme. PMID:21144880

  20. Inhibition of microRNA-1 attenuates hypoxia/re-oxygenation-induced apoptosis of cardiomyocytes by directly targeting Bcl-2 but not GADD45Beta

    PubMed Central

    Zhai, Changlin; Tang, Guanmin; Peng, Lei; Hu, Huilin; Qian, Gang; Wang, Shijun; Yao, Jiankang; Zhang, Xiaoping; Fang, Ying; Yang, Shuang; Zhang, Xiumei

    2015-01-01

    MicroRNAs are small non-coding RNAs that are able to regulate gene expression and play important roles in some biological and pathological processes, including the myocardial ischemia/reperfusion (I/R) injury. Recent findings demonstrated that miR-1 exacerbated I/R-induced injury. This study was to investigate theanti-apoptotic property of miR-1 inhibition and the potential regulatory mechanism. Results showed miR-1 expression reduced in the heart of rats undergoing myocardial I/R and the cardiomyocytes receiving hypoxia/reoxygenation (H/R) injury, but the serum miR-1 expression increased. The targets of miR-1 were predicted by cDNA microarray, and Bcl-2 and GADD45β were selected as candidate targets. Western blot assay and qPCR showed Bcl-2 and GADD45β protein and mRNA expressions increased after I/R injury and H/R injury. Bcl-2 was a direct target of miR-1 as shown in previous studies. Luciferase assay and Western blot assay revealed GADD45β was a direct target of miR-1, and miR-1 suppressed GADD45β expression via binding to its 3’UTR. Furthermore, miR-1 inhibition increased Bcl-2 expression and reduced IA/AAR (infarct area/area at risk) ratio and cell apoptosis in rats undergoing myocardial I/R as well as in cardiomyocytes receiving H/R injury. Importantly, Bcl-2 knockdown restored these consequences following miR-1 inhibition. However, GADD45β knockdown reduced IA/AAR ratio and cell apoptosis in vivo and in vitro, but failed torestore above consequences after miR-1 inhibition. In conclusion miR-1 inhibition protects against H/R-induced apoptosis of myocytes by directly targeting Bcl-2 but not GADD45β. PMID:26692938

  1. Selection of novel reference genes for use in the human central nervous system: a BrainNet Europe Study.

    PubMed

    Durrenberger, Pascal F; Fernando, Francisca S; Magliozzi, Roberta; Kashefi, Samira N; Bonnert, Timothy P; Ferrer, Isidro; Seilhean, Danielle; Nait-Oumesmar, Brahim; Schmitt, Andrea; Gebicke-Haerter, Peter J; Falkai, Peter; Grünblatt, Edna; Palkovits, Miklos; Parchi, Piero; Capellari, Sabina; Arzberger, Thomas; Kretzschmar, Hans; Roncaroli, Federico; Dexter, David T; Reynolds, Richard

    2012-12-01

    The use of an appropriate reference gene to ensure accurate normalisation is crucial for the correct quantification of gene expression using qPCR assays and RNA arrays. The main criterion for a gene to qualify as a reference gene is a stable expression across various cell types and experimental settings. Several reference genes are commonly in use but more and more evidence reveals variations in their expression due to the presence of on-going neuropathological disease processes, raising doubts concerning their use. We conducted an analysis of genome-wide changes of gene expression in the human central nervous system (CNS) covering several neurological disorders and regions, including the spinal cord, and were able to identify a number of novel stable reference genes. We tested the stability of expression of eight novel (ATP5E, AARS, GAPVD1, CSNK2B, XPNPEP1, OSBP, NAT5 and DCTN2) and four more commonly used (BECN1, GAPDH, QARS and TUBB) reference genes in a smaller cohort using RT-qPCR. The most stable genes out of the 12 reference genes were tested as normaliser to validate increased levels of a target gene in CNS disease. We found that in human post-mortem tissue the novel reference genes, XPNPEP1 and AARS, were efficient in replicating microarray target gene expression levels and that XPNPEP1 was more efficient as a normaliser than BECN1, which has been shown to change in expression as a consequence of neuronal cell loss. We provide herein one more suitable novel reference gene, XPNPEP1, with no current neuroinflammatory or neurodegenerative associations that can be used for gene quantitative gene expression studies with human CNS post-mortem tissue and also suggest a list of potential other candidates. These data also emphasise the importance of organ/tissue-specific stably expressed genes as reference genes for RNA studies.

  2. Effects of ischemic preconditioning and iloprost on myocardial ischemia-reperfusion damage in rats.

    PubMed

    Ay, Yasin; Kara, Ibrahim; Aydin, Cemalettin; Ay, Nuray Kahraman; Teker, Melike Elif; Senol, Serkan; Inan, Bekir; Basel, Halil; Uysal, Omer; Zeybek, Rahmi

    2013-01-01

    This study investigates the effects of cardiac ischemic preconditioning and iloprost on reperfusion damage in rats with myocardial ischemia/reperfusion. 38 male Wistar Albino rats used in this study were divided into 5 groups. The control group (Group 1) (n=6), ischemia/reperfusion (IR) group (Group 2) (n=8), cardiac ischemic preconditioning (CIP) group (Group 3) (n=8), iloprost (ILO) group (Group 4) (n=8), and cardiac ischemic preconditioning + iloprost (CIP+ILO) group (Group 5) (n=8). Pre-ischemia, 15 minutes post-ischemia, 45 minutes post-reperfusion, mean blood pressure (MBP), and heart rates (HR) were recorded. The rate-pressure product (RPP) was calculated. Post-reperfusion plasma creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin (cTn) vlaues, and infarct size/area at risk (IS/AAR) were calculated from myocardial tissue samples. Arrhythmia and ST segment elevations were evaluated during the ischemia and reperfusion stages. Although the MBP, HR, RPP values, biochemical parameters of CK-MB and LDH levels, IS/AAR rates, ST segment elevation values were found to be similar in CIP and CIP+ILO groups and the IR and ILO groups (p>0.05), CIP-containing group values had a positively meaningful difference (p<0.05) compared with the IR and ILO group. While mild-moderate findings of damage were observed in Group 3 and Group 5, severely findings of damage were releaved in Group 2 and Group 4. The arrhythmia score of the ILO group was meaningfully lower (F: 41.4, p<0.001) than the IR group. We can conclude that the effects of myocardial reperfusion damage can be reduced by cardiac ischemic preconditioning, intravenous iloprost reduced the incidence of ventricular arrhythmia associated with reperfusion, and its use with CIP caused no additional changes.

  3. First hydrothermal discoveries on the Australian-Antarctic Ridge: Discharge sites, plume chemistry, and vent organisms

    NASA Astrophysics Data System (ADS)

    Hahm, Doshik; Baker, Edward T.; Siek Rhee, Tae; Won, Yong-Jin; Resing, Joseph A.; Lupton, John E.; Lee, Won-Kyung; Kim, Minjeong; Park, Sung-Hyun

    2015-09-01

    The Australian-Antarctic Ridge (AAR) is one of the largest unexplored regions of the global mid-ocean ridge system. Here, we report a multiyear effort to locate and characterize hydrothermal activity on two first-order segments of the AAR: KR1 and KR2. To locate vent sites on each segment, we used profiles collected by Miniature Autonomous Plume Recorders on rock corers during R/V Araon cruises in March and December of 2011. Optical and oxidation-reduction-potential anomalies indicate multiple active sites on both segments. Seven profiles on KR2 found 3 sites, each separated by ˜25 km. Forty profiles on KR1 identified 17 sites, some within a few kilometer of each other. The spatial density of hydrothermal activity along KR1 and KR2 (plume incidence of 0.34) is consistent with the global trend for a spreading rate of ˜70 mm/yr. The densest area of hydrothermal activity, named "Mujin," occurred along the 20 km-long inflated section near the segment center of KR1. Continuous plume surveys conducted in January-February of 2013 on R/V Araon found CH4/3He (1 - 15 × 106) and CH4/Mn (0.01-0.5) ratios in the plume samples, consistent with a basaltic-hosted system and typical of ridges with intermediate spreading rates. Additionally, some of the plume samples exhibited slightly higher ratios of H2/3He and Fe/Mn than others, suggesting that those plumes are supported by a younger hydrothermal system that may have experienced a recent eruption. The Mujin-field was populated by Kiwa crabs and seven-armed Paulasterias starfish previously recorded on the East Scotia Ridge, raising the possibility of circum-Antarctic biogeographic connections of vent fauna.

  4. Teachers' and Parents' Perspectives on a Curricular Subject of "Religion and Spirituality" for Indian Schools: A Pilot Study Toward School Mental Health Program.

    PubMed

    Ramakrishnan, Parameshwaran; Baccari, Andrew; Ramachandran, Uma; Ahmed, Syed Faiz; Koenig, Harold G

    2017-08-17

    Religious-spiritual (R/S) education helps medical students cope with caregiving stress and gain skills in interpersonal empathy needed for clinical care. Such R/S education has been introduced into K-12 and college curricula in some developed nations and has been found to positively impact student's mental health. Such a move has not yet been seen in the Indian education system. This paper aimed to examine perspectives of teachers and parents in India on appropriateness, benefits, and challenges of including R/S education into the school curriculum and also to gather their impressions on how a R/S curriculum might promote students' health. A cross-sectional study of religiously stratified sample of teachers and parents was initiated in three preselected schools in India and the required sample size (N = 300) was reached through snowballing technique. A semi-structured questionnaire, with questions crafted from "Religion and Spirituality in Medicine, Physicians Perspective" (RSMPP) and "American Academy of Religion's (AAR) Guidelines for Religious Literacy," was used to determine participants' perspectives. Findings revealed that teachers' and parents' "comfort in integrating R/S into school curriculum" was associated with their gender (OR 1.68), education status (OR 1.05), and intrinsic religiosity (OR 1.05). Intrinsic religiosity was significantly (p = 0.025) high among parents while "intrinsic spirituality" was high (p = 0.020) among teachers. How participants' R/S characteristics influence their support of R/S education in school is discussed. In conclusion, participants believe R/S education will fosters students' emotional health and interpersonal skills needed for social leadership. A curriculum that incorporates R/S education, which is based on AAR guidelines and clinically validated interpersonal spiritual care tools would be acceptable to both teachers and parents.

  5. Designing logical codon reassignment - Expanding the chemistry in biology.

    PubMed

    Dumas, Anaëlle; Lercher, Lukas; Spicer, Christopher D; Davis, Benjamin G

    2015-01-01

    Over the last decade, the ability to genetically encode unnatural amino acids (UAAs) has evolved rapidly. The programmed incorporation of UAAs into recombinant proteins relies on the reassignment or suppression of canonical codons with an amino-acyl tRNA synthetase/tRNA (aaRS/tRNA) pair, selective for the UAA of choice. In order to achieve selective incorporation, the aaRS should be selective for the designed tRNA and UAA over the endogenous amino acids and tRNAs. Enhanced selectivity has been achieved by transferring an aaRS/tRNA pair from another kingdom to the organism of interest, and subsequent aaRS evolution to acquire enhanced selectivity for the desired UAA. Today, over 150 non-canonical amino acids have been incorporated using such methods. This enables the introduction of a large variety of structures into proteins, in organisms ranging from prokaryote, yeast and mammalian cells lines to whole animals, enabling the study of protein function at a level that could not previously be achieved. While most research to date has focused on the suppression of 'non-sense' codons, recent developments are beginning to open up the possibility of quadruplet codon decoding and the more selective reassignment of sense codons, offering a potentially powerful tool for incorporating multiple amino acids. Here, we aim to provide a focused review of methods for UAA incorporation with an emphasis in particular on the different tRNA synthetase/tRNA pairs exploited or developed, focusing upon the different UAA structures that have been incorporated and the logic behind the design and future creation of such systems. Our hope is that this will help rationalize the design of systems for incorporation of unexplored unnatural amino acids, as well as novel applications for those already known.

  6. High FIB-4 index as an independent risk factor of prevalent chronic kidney disease in patients with nonalcoholic fatty liver disease.

    PubMed

    Xu, Huang-Wei; Hsu, Yung-Chien; Chang, Chia-Hao; Wei, Kuo-Liang; Lin, Chun-Liang

    2016-03-01

    Growing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is linked to an increased risk for chronic kidney disease (CKD); liver fibrosis with biopsy-proven NAFLD has also been shown to associate with an increased risk of CKD. This study compares the diagnostic performance of simple noninvasive tests in identifying prevalent CKD among individuals with ultrasonography-diagnosed NAFLD. A total of 755 with ultrasonography-diagnosed NAFLD were included. Estimated glomerular filtration rate and noninvasive markers for hepatic fibrosis: aspartate transaminase to alanine transaminase ratio (AAR), aspartate transaminase to platelet ratio index (APRI), FIB-4 score, NAFLD fibrosis score (NFS) and BARD score were assessed. Binary logistic regression to generate a propensity score and receiver operating characteristic curves were developed for each of the noninvasive markers for predicting CKD, and the area under the receiver operating characteristic curve was greatest for FIB-4 score (0.750), followed by NFS (0.710), AAR (0.594), APRI (0.587), and BARD score (0.561). A cut-off value of 1.100 for FIB-4 score gave a sensitivity of 68.85% and a specificity of 71.07% for predicting CKD. The positive predictive value and negative predictive value were 37.50 and 90.05%, respectively. In multiple logistic regression analysis, only FIB-4 score ≧1.100 (OR 2.660, 95% CI 1.201-5.889; p = .016), older age, higher diastolic blood pressure and higher uric acid were independent predictors of CKD. High noninvasive fibrosis score is associated with an increased risk of prevalent CKD; the FIB-4 is the better predictor. With a cut-off value of 1.100 for FIB-4, it is useful in excluding the presence of CKD in patients with NAFLD.

  7. Lightweight deformable mirrors for future space telescopes

    NASA Astrophysics Data System (ADS)

    Patterson, Keith

    This thesis presents a concept for ultra-lightweight deformable mirrors based on a thin substrate of optical surface quality coated with continuous active piezopolymer layers that provide modes of actuation and shape correction. This concept eliminates any kind of stiff backing structure for the mirror surface and exploits micro-fabrication technologies to provide a tight integration of the active materials into the mirror structure, to avoid actuator print-through effects. Proof-of-concept, 10-cm-diameter mirrors with a low areal density of about 0.5 kg/m2 have been designed, built and tested to measure their shape-correction performance and verify the models used for design. The low cost manufacturing scheme uses replication techniques, and strives for minimizing residual stresses that deviate the optical figure from the master mandrel. It does not require precision tolerancing, is lightweight, and is therefore potentially scalable to larger diameters for use in large, modular space telescopes. Other potential applications for such a laminate could include ground-based mirrors for solar energy collection, adaptive optics for atmospheric turbulence, laser communications, and other shape control applications. The immediate application for these mirrors is for the Autonomous Assembly and Reconfiguration of a Space Telescope (AAReST) mission, which is a university mission under development by Caltech, the University of Surrey, and JPL. The design concept, fabrication methodology, material behaviors and measurements, mirror modeling, mounting and control electronics design, shape control experiments, predictive performance analysis, and remaining challenges are presented herein. The experiments have validated numerical models of the mirror, and the mirror models have been used within a model of the telescope in order to predict the optical performance. A demonstration of this mirror concept, along with other new telescope technologies, is planned to take place during

  8. Effect of Lactation on myocardial vulnerability to ischemic insult in rats

    PubMed Central

    Askari, Sahar; Imani, Alireza; Sadeghipour, Hamidreza; Faghihi, Mahdieh; Edalatyzadeh, Zohreh; Choopani, Samira; Karimi, Nasser; Fatima, Sulail

    2017-01-01

    Background Cardiovascular diseases are the leading cause of mortality and long-term disability worldwide. Various studies have suggested a protective effect of lactation in reducing the risk of cardiovascular diseases. Objective This study was designed to assess the effects of pregnancy and lactation on the vulnerability of the myocardium to an ischemic insult. Methods Eighteen female rats were randomly divided into three groups: ischemia-reperfusion (IR), in which the hearts of virgin rats underwent IR (n = 6); lactating, in which the rats nursed their pups for 3 weeks and the maternal hearts were then submitted to IR (n = 6); and non-lactating, in which the pups were separated after birth and the maternal hearts were submitted to IR (n = 6). Outcome measures included heart rate (HR), left ventricular developed pressure (LVDP), rate pressure product (RPP), ratio of the infarct size to the area at risk (IS/AAR %), and ventricular arrhythmias - premature ventricular contraction (PVC) and ventricular tachycardia (VT). Results The IS/AAR was markedly decreased in the lactating group when compared with the non-lactating group (13.2 ± 2.5 versus 39.7 ± 3.5, p < 0.001) and the IR group (13.2 ± 2.5 versus 34.0 ± 4.7, p < 0.05). The evaluation of IR-induced ventricular arrhythmias indicated that the number of compound PVCs during ischemia, and the number and duration of VTs during ischemia and in the first 5 minutes of reperfusion in the non-lactating group were significantly (p < 0.05) higher than those in the lactating and IR groups. Conclusion Lactation induced early-onset cardioprotective effects, while rats that were not allowed to nurse their pups were more susceptible to myocardial IR injury. PMID:28444063

  9. Spinophilin Is Indispensable for the α2B Adrenergic Receptor-Elicited Hypertensive Response.

    PubMed

    Che, Pulin; Chen, Yunjia; Lu, Roujian; Peng, Ning; Gannon, Mary; Wyss, J Michael; Jiao, Kai; Wang, Qin

    2015-01-01

    The α2 adrenergic receptor (AR) subtypes are important for blood pressure control. When activated, the α2A subtype elicits a hypotensive response whereas the α2B subtype mediates a hypertensive effect that counteracts the hypotensive response by the α2A subtype. We have previously shown that spinophilin attenuates the α2AAR-dependent hypotensive response; in spinophilin null mice, this response is highly potentiated. In this study, we demonstrate that spinophilin impedes arrestin-dependent phosphorylation and desensitization of the α2BAR subtype by competing against arrestin binding to this receptor subtype. The Del301-303 α2BAR, a human variation that shows impaired phosphorylation and desensitization and is linked to hypertension in certain populations, exhibits preferential interaction with spinophilin over arrestin. Furthermore, Del301-303 α2BAR-induced ERK signaling is quickly desensitized in cells without spinophilin expression, showing a profile similar to that induced by the wild type receptor in these cells. Together, these data suggest a critical role of spinophilin in sustaining α2BAR signaling. Consistent with this notion, our in vivo study reveals that the α2BAR-elicited hypertensive response is diminished in spinophilin deficient mice. In arrestin 3 deficient mice, where the receptor has a stronger binding to spinophilin, the same hypertensive response is enhanced. These data suggest that interaction with spinophilin is indispensable for the α2BAR to elicit the hypertensive response. This is opposite of the negative role of spinophilin in regulating α2AAR-mediated hypotensive response, suggesting that spinophilin regulation of these closely related receptor subtypes can result in distinct functional outcomes in vivo. Thus, spinophilin may represent a useful therapeutic target for treatment of hypertension.

  10. The effects of automated artifact removal algorithms on electroencephalography-based Alzheimer's disease diagnosis

    PubMed Central

    Cassani, Raymundo; Falk, Tiago H.; Fraga, Francisco J.; Kanda, Paulo A. M.; Anghinah, Renato

    2014-01-01

    Over the last decade, electroencephalography (EEG) has emerged as a reliable tool for the diagnosis of cortical disorders such as Alzheimer's disease (AD). EEG signals, however, are susceptible to several artifacts, such as ocular, muscular, movement, and environmental. To overcome this limitation, existing diagnostic systems commonly depend on experienced clinicians to manually select artifact-free epochs from the collected multi-channel EEG data. Manual selection, however, is a tedious and time-consuming process, rendering the diagnostic system “semi-automated.” Notwithstanding, a number of EEG artifact removal algorithms have been proposed in the literature. The (dis)advantages of using such algorithms in automated AD diagnostic systems, however, have not been documented; this paper aims to fill this gap. Here, we investigate the effects of three state-of-the-art automated artifact removal (AAR) algorithms (both alone and in combination with each other) on AD diagnostic systems based on four different classes of EEG features, namely, spectral, amplitude modulation rate of change, coherence, and phase. The three AAR algorithms tested are statistical artifact rejection (SAR), blind source separation based on second order blind identification and canonical correlation analysis (BSS-SOBI-CCA), and wavelet enhanced independent component analysis (wICA). Experimental results based on 20-channel resting-awake EEG data collected from 59 participants (20 patients with mild AD, 15 with moderate-to-severe AD, and 24 age-matched healthy controls) showed the wICA algorithm alone outperforming other enhancement algorithm combinations across three tasks: diagnosis (control vs. mild vs. moderate), early detection (control vs. mild), and disease progression (mild vs. moderate), thus opening the doors for fully-automated systems that can assist clinicians with early detection of AD, as well as disease severity progression assessment. PMID:24723886

  11. Meteorological Data Inventory, Southern California, Coastal Zone, Ragged Point (San Luis Obispo County) to Mexican Border.

    DTIC Science & Technology

    1985-12-01

    OBSERVATION TI.E 5 M/P. REMARKS/CERTI F CATION: SUBAREA CODE A7FOREIGN N . ..-. QUAD) INDEX NO. 24- 65 DAY OCT. NOV. DEC. JAN. FEB. AAR. APR. MAI/ JUNE JULY...I E . 33-38-10 117-10-44 I9/046- 5 40 1907 1960 601.9 1909 100.6 1961 309.3 29200- 65 - * ELSINO 6EP 33-41-00 117-23-01 005/006- 5 390 1966 170.1 1970 34...1941 102:: 1961 316.1 5 47-1 L*UN 8EC NARAE 933.3 1- 65 719’ 1927 119?8 74-3.7 1941 1 1 1 1961 31. A65©-ooL LAGURA 86ACH 2-L*8*WAT 01 3 3-,3303 117:.-4o

  12. A New Species of the Genus Kiwa (Decapoda: Anomura) from the Hydrothermal Vent of the Australia-Antarctic Ridge

    NASA Astrophysics Data System (ADS)

    Won, Y. J.; Lee, S. H.; Lee, W. K.

    2014-12-01

    Due to extreme weather conditions and remoteness to access, the great part of the Southern Ocean remains to be explored. Therefore, little is known about the Circum-Antarctic Ridge (CAR) system and its hydrothermal vent ecosystem underlying the Southern Ocean. We report the first discovery of a new deep-sea hydrothermal vent field and a new anomuran species from the Australia-Antarctic Ridge (AAR), the highest latitude (62°S; 158°E) explored in the Southern Ocean up to date. At this site, a new anomuran species which belongs to the genus Kiwa known as 'yeti crabs' was found. Morphologically, this species has characteristics of the genus Kiwa, including fifth pereopod inserted below sterna plastron, third sternite strongly produced anteriorly, and eyes extremely reduced. However, the new species differs from the other known species of Kiwa, K. hirsuta and K. puravida, showing relatively short rostrum and slender dactylus on second to fourth pereopods. Phylogenetic analysis using DNA sequences of eight genetic loci also supported the result of morphological analysis, confirming this species as a new Kiwa species, Kiwa n. sp. In addition, phylogenetic tree revealed the evolutionary relationship among the Kiwa species, presenting the Kiwa n. sp. as the sister species to K. puravida which inhabits the methane cold seep on the Pacific continental slope off Costa Rica. Considering the geography and the physicochemical environment, this unlikely result casts a mystery to be solved through further taxon sampling particularly from as-yet-unexplored vents and seeps. Discovery of the hydrothermal vent and Kiwa n. sp. from the AAR segment is significant because this site is located in the high latitude of the southern hemisphere and it is the region affected by the Antarctic Circumpolar Current (ACC). Future research on the relation of Kiwa n. sp. and the other Kiwa species affected by the ACC will provide an idea about the biogeography and the evolutionary connections of the

  13. Dating and biogeographical patterns in the sea slug genus Acanthodoris Gray, 1850 (Mollusca, Gastropoda, Nudibranchia).

    PubMed

    Hallas, Joshua M; Brian Simison, W; Gosliner, Terrence M

    2016-04-01

    Recent studies investigating vicariance and dispersal have been focused on correlating major geological events with instances of taxonomic expansion by incorporating the fossil record with molecular clock analyses. However, this approach becomes problematic for soft-bodied organisms that are poorly represented in the fossil record. Here, we estimate the phylogenetic relationships of the nudibranch genus Acanthodoris Gray, 1850 using three molecular markers (16S, COI, H3), and then test two alternative geologically calibrated molecular clock scenarios in BEAST and their effect on ancestral area reconstruction (AAR) estimates employed in LAGRANGE. The global temperate distribution of Acanthodoris spans multiple geological barriers, including the Bering Strait (∼5.32 Mya) and the Baja Peninsula (∼5.5 Mya), both of which are used in our dating estimates. The expansion of the Atlantic Ocean (∼95-105 Mya) is also used to calibrate the relationship between A. falklandica Eliot, 1905 and A. planca Fahey and Valdés, 2005, which are distributed in southern Chile and South Africa respectively. Phylogenetic analyses recovered strong biogeographical signal and recovered two major clades representing northern and southern hemispheric distributions of Acanthodoris. When all three geological events are applied to the calibration analyses, the age for Acanthodoris is estimated to be mid-Cretaceous. When the expansion of the Atlantic Ocean is excluded from our analyses, however, Acanthodoris is estimated to be much younger, with a divergence time estimate during the Miocene. Regardless of divergence estimates, our AAR suggests that Acanthodoris may have origins in the Atlantic Ocean with the Atlantic acting as a dispersal point to the northeastern Pacific. These results suggest that Acanthodoris exhibits a rare instance of western trans-arctic expansion. This study also shows that northeast Pacific specimens of A. pilosa should be regarded as A. atrogriseata and that A

  14. Recognition of upper airway and surrounding structures at MRI in pediatric PCOS and OSAS

    NASA Astrophysics Data System (ADS)

    Tong, Yubing; Udupa, J. K.; Odhner, D.; Sin, Sanghun; Arens, Raanan

    2013-03-01

    Obstructive Sleep Apnea Syndrome (OSAS) is common in obese children with risk being 4.5 fold compared to normal control subjects. Polycystic Ovary Syndrome (PCOS) has recently been shown to be associated with OSAS that may further lead to significant cardiovascular and neuro-cognitive deficits. We are investigating image-based biomarkers to understand the architectural and dynamic changes in the upper airway and the surrounding hard and soft tissue structures via MRI in obese teenage children to study OSAS. At the previous SPIE conferences, we presented methods underlying Fuzzy Object Models (FOMs) for Automatic Anatomy Recognition (AAR) based on CT images of the thorax and the abdomen. The purpose of this paper is to demonstrate that the AAR approach is applicable to a different body region and image modality combination, namely in the study of upper airway structures via MRI. FOMs were built hierarchically, the smaller sub-objects forming the offspring of larger parent objects. FOMs encode the uncertainty and variability present in the form and relationships among the objects over a study population. Totally 11 basic objects (17 including composite) were modeled. Automatic recognition for the best pose of FOMs in a given image was implemented by using four methods - a one-shot method that does not require search, another three searching methods that include Fisher Linear Discriminate (FLD), a b-scale energy optimization strategy, and optimum threshold recognition method. In all, 30 multi-fold cross validation experiments based on 15 patient MRI data sets were carried out to assess the accuracy of recognition. The results indicate that the objects can be recognized with an average location error of less than 5 mm or 2-3 voxels. Then the iterative relative fuzzy connectedness (IRFC) algorithm was adopted for delineation of the target organs based on the recognized results. The delineation results showed an overall FP and TP volume fraction of 0.02 and 0.93.

  15. Evaluating Diagnostic Accuracy of Noninvasive Tests in Assessment of Significant Liver Fibrosis in Chronic Hepatitis C Egyptian Patients.

    PubMed

    Omran, Dalia; Zayed, Rania A; Nabeel, Mohammed M; Mobarak, Lamiaa; Zakaria, Zeinab; Farid, Azza; Hassany, Mohamed; Saif, Sameh; Mostafa, Muhammad; Saad, Omar Khalid; Yosry, Ayman

    2018-05-01

    Stage of liver fibrosis is critical for treatment decision and prediction of outcomes in chronic hepatitis C (CHC) patients. We evaluated the diagnostic accuracy of transient elastography (TE)-FibroScan and noninvasive serum markers tests in the assessment of liver fibrosis in CHC patients, in reference to liver biopsy. One-hundred treatment-naive CHC patients were subjected to liver biopsy, TE-FibroScan, and eight serum biomarkers tests; AST/ALT ratio (AAR), AST to platelet ratio index (APRI), age-platelet index (AP index), fibrosis quotient (FibroQ), fibrosis 4 index (FIB-4), cirrhosis discriminant score (CDS), King score, and Goteborg University Cirrhosis Index (GUCI). Receiver operating characteristic curves were constructed to compare the diagnostic accuracy of these noninvasive methods in predicting significant fibrosis in CHC patients. TE-FibroScan predicted significant fibrosis at cutoff value 8.5 kPa with area under the receiver operating characteristic (AUROC) 0.90, sensitivity 83%, specificity 91.5%, positive predictive value (PPV) 91.2%, and negative predictive value (NPV) 84.4%. Serum biomarkers tests showed that AP index and FibroQ had the highest diagnostic accuracy in predicting significant liver fibrosis at cutoff 4.5 and 2.7, AUROC was 0.8 and 0.8 with sensitivity 73.6% and 73.6%, specificity 70.2% and 68.1%, PPV 71.1% and 69.8%, and NPV 72.9% and 72.3%, respectively. Combined AP index and FibroQ had AUROC 0.83 with sensitivity 73.6%, specificity 80.9%, PPV 79.6%, and NPV 75.7% for predicting significant liver fibrosis. APRI, FIB-4, CDS, King score, and GUCI had intermediate accuracy in predicting significant liver fibrosis with AUROC 0.68, 0.78, 0.74, 0.74, and 0.67, respectively, while AAR had low accuracy in predicting significant liver fibrosis. TE-FibroScan is the most accurate noninvasive alternative to liver biopsy. AP index and FibroQ, either as individual tests or combined, have good accuracy in predicting significant liver fibrosis

  16. The selective NLRP3-inflammasome inhibitor MCC950 reduces infarct size and preserves cardiac function in a pig model of myocardial infarction.

    PubMed

    van Hout, Gerardus P J; Bosch, Lena; Ellenbroek, Guilielmus H J M; de Haan, Judith J; van Solinge, Wouter W; Cooper, Matthew A; Arslan, Fatih; de Jager, Saskia C A; Robertson, Avril A B; Pasterkamp, Gerard; Hoefer, Imo E

    2017-03-14

    Myocardial infarction (MI) triggers an intense inflammatory response that is associated with infarct expansion and is detrimental for cardiac function. Interleukin (IL)-1β and IL-18 are key players in this response and are controlled by the NLRP3-inflammasome. In the current study, we therefore hypothesized that selective inhibition of the NLRP3-inflammasome reduces infarct size and preserves cardiac function in a porcine MI model. Thirty female landrace pigs were subjected to 75 min transluminal balloon occlusion and treated with the NLRP3-inflammasome inhibitor MCC950 (6 or 3 mg/kg) or placebo for 7 days in a randomized, blinded fashion. After 7 days, 3D-echocardiography was performed to assess cardiac function and Evans blue/TTC double staining was executed to assess the area at risk (AAR) and infarct size (IS). The IS/AAR was lower in the 6 mg/kg group (64.6 ± 8.8%, P = 0.004) and 3 mg/kg group (69.7 ± 7.2%, P = 0.038) compared with the control group (77.5 ± 6.3%). MCC950 treatment markedly preserved left ventricular ejection fraction in treated animals (6 mg/kg 47 ± 8%, P = 0.001; 3 mg/kg 45 ± 7%, P = 0.031; control 37 ± 6%). Myocardial neutrophil influx was attenuated in treated compared with non-treated animals (6 mg/kg 132 ± 72 neutrophils/mm2, P = 0.035; 3 mg/kg 207 ± 210 neutrophils/mm2, P = 0.5; control 266 ± 158 neutrophils/mm2). Myocardial IL-1β levels were dose-dependently reduced in treated animals. NLRP3-inflammasome inhibition reduces infarct size and preserves cardiac function in a randomized, blinded translational large animal MI model. Hence, NLRP3-inflammasome inhibition may have therapeutic potential in acute MI patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  17. Simulated performance of biomass gasification based combined power and refrigeration plant for community scale application

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

    Chattopadhyay, S., E-mail: suman.mech09@gmail.com; Mondal, P., E-mail: mondal.pradip87@gmail.com; Ghosh, S., E-mail: sudipghosh.becollege@gmail.com

    Thermal performance analysis and sizing of a biomass gasification based combined power and refrigeration plant (CPR) is reported in this study. The plant is capable of producing 100 kWe of electrical output while simultaneously producing a refrigeration effect, varying from 28-68 ton of refrigeration (TR). The topping gas turbine cycle is an indirectly heated all-air cycle. A combustor heat exchanger duplex (CHX) unit burns producer gas and transfer heat to air. This arrangement avoids complex gas cleaning requirements for the biomass-derived producer gas. The exhaust air of the topping GT is utilized to run a bottoming ammonia absorption refrigeration (AAR)more » cycle via a heat recovery steam generator (HRSG), steam produced in the HRSG supplying heat to the generator of the refrigeration cycle. Effects of major operating parameters like topping cycle pressure ratio (r{sub p}) and turbine inlet temperature (TIT) on the energetic performance of the plant are studied. Energetic performance of the plant is evaluated via energy efficiency, required biomass consumption and fuel energy savings ratio (FESR). The FESR calculation method is significant for indicating the savings in fuel of a combined power and process heat plant instead of separate plants for power and process heat. The study reveals that, topping cycle attains maximum power efficiency of 30%in pressure ratio range of 8-10. Up to a certain value of pressure ratio the required air flow rate through the GT unit decreases with increase in pressure ratio and then increases with further increase in pressure ratio. The capacity of refrigeration of the AAR unit initially decreases up to a certain value of topping GT cycle pressure ratio and then increases with further increase in pressure ratio. The FESR is found to be maximized at a pressure ratio of 9 (when TIT=1100°C), the maximum value being 53%. The FESR is higher for higher TIT. The heat exchanger sizing is also influenced by the topping cycle pressure

  18. Generation of Alfvenic Double Layers, Formation of Auroral Arcs, and Their Impact on Energy and Momentum Transfer in M-I Coupling System

    NASA Astrophysics Data System (ADS)

    Song, Y.; Lysak, R. L.

    2017-12-01

    Parallel electrostatic electric fields provide a powerful mechanism to accelerate auroral particles to high energy in the auroral acceleration region (AAR), creating both quasi-static and Alfvenic discrete aurorae. The total field-aligned current can be written as J||total=J||+J||D, where the displacement current is denoted as J||D=(1/4π)(∂E||/∂t), which describes the E||-generation (Song and Lysak, 2006). The generation of the total field-aligned current is related to spatial gradients of the parallel vorticity caused by the axial torque acting on field-aligned flux tubes in M-I coupling system. It should be noticed that parallel electric fields are not produced by the field-aligned current. In fact, the E||-generation is caused by Alfvenic interaction in the M-I coupling system, and is favored by a low plasma density and the enhanced localized azimuthal magnetic flux. We suggest that the nonlinear interaction of incident and reflected Alfven wave packets in the AAR can create reactive stress concentration, and therefore can generate the parallel electrostatic electric fields together with a seed low density cavity. The generated electric fields will quickly deepen the seed low density cavity, which can effectively create even stronger electrostatic electric fields. The electrostatic electric fields nested in a low density cavity and surrounded by enhanced azimuthal magnetic flux constitute Alfvenic electromagnetic plasma structures, such as Alfvenic Double Layers (DLs). The Poynting flux carried by Alfven waves can continuously supply energy from the generator region to the auroral acceleration region, supporting and sustaining Alfvenic DLs with long-lasting electrostatic electric fields which accelerate auroral particles to high energy. The generation of parallel electric fields and the formation of auroral arcs can redistribute perpendicular mechanical and magnetic stresses in auroral flux tubes, decoupling the magnetosphere from ionosphere drag locally

  19. Modelling geomorphic responses to human perturbations: Application to the Kander river, Switzerland

    NASA Astrophysics Data System (ADS)

    Ramirez, Jorge; Zischg, Andreas; Schürmann, Stefan; Zimmermann, Markus; Weingartner, Rolf; Coulthard, Tom; Keiler, Margreth

    2017-04-01

    Before 1714 the Kander river (Switzerland) flowed into the Aare river causing massive flooding and for this reason the Kander river was deviated (Kander correction) to lake Thun. The Kander correction was a pioneering hydrological project and induced a major human change to the landscape, but had unintended hydrological and geomorphic impacts that cascaded upstream and downstream. For example doubling the catchment area of Lake Thun, which gave rise to major flood problems, cessation of direct sediment delivery to the Aare, and sediment flux to lake Thun forming the Kander delta. More importantly the Kander correction shortened the Kander river and substantially increased the slope and bed shear of the Kander upstream from the correction. Consequently impacts of the correction cascaded upstream as a migrating knickpoint and eroded the river channel at unprecedented rates. Today we may have at our disposal the theoretical and empirical foundations to foresee the consequences of human intervention into natural systems. One method to investigate such geomorphic changes are numerical models that estimate the evolution of rivers by simulating the movement of water and sediment. Although much progress has been made in the development of these geomorphic models, few models have been tested in circumstances with rare perturbations and extreme forcings. As such, it remains uncertain if geomorphic models are useful and stable in extreme situations that include large movements of sediment and water. Here, in this study, we use historic maps and documents to develop a detailed geomorphic model of the Kander river starting in the year 1714. We use this model to simulate the extreme geomorphic events that preceded the deviation of the Kander river into Lake Thun and simulate changes to the river until conditions become relatively stable. We test our model by replicating long term impacts to the river that include 1) rates of incision within the correction, 2) knickpoint

  20. No post-conditioning in the human heart with thrombolysis in myocardial infarction flow 2-3 on admission.

    PubMed

    Roubille, F; Mewton, N; Elbaz, M; Roth, O; Prunier, F; Cung, T T; Piot, C; Roncalli, J; Rioufol, G; Bonnefoy-Cudraz, E; Wiedemann, J Y; Furber, A; Jacquemin, L; Willoteaux, S; Abi-Khallil, W; Sanchez, I; Finet, G; Sibellas, F; Ranc, S; Boussaha, I; Croisille, P; Ovize, M

    2014-07-01

    Proof-of-concept evidence suggests that mechanical ischaemic post-conditioning (PostC) reduces infarct size when applied immediately after culprit coronary artery re-opening in ST-elevation myocardial infarction (STEMI) patients with thrombolysis in myocardial infarction 0-1 (TIMI 0-1) flow grade at admission. Whether PostC might also be protective in patients with a TIMI 2-3 flow grade on admission (corresponding to a delayed application of the post-conditioning algorithm) remains undetermined. In this multi-centre, randomized, single-blinded, controlled study, STEMI patients with a 2-3 TIMI coronary flow grade at admission underwent direct stenting of the culprit lesion, followed (PostC group) or not (control group) by four cycles of (1 min inflation/1 min deflation) of the angioplasty balloon to trigger post-conditioning. Infarct size was assessed both by cardiac magnetic resonance at Day 5 (primary endpoint) and cardiac enzymes release (secondary endpoint). Ninety-nine patients were prospectively enrolled. Baseline characteristics were comparable between control and PostC groups. Despite comparable size of area at risk (AAR) (38 ± 12 vs. 38 ± 13% of the LV circumference, respectively, P = 0.89) and similar time from onset to intervention (249 ± 148 vs. 263 ± 209 min, respectively, P = 0.93) in the two groups, PostC did not significantly reduce cardiac magnetic resonance infarct size (23 ± 17 and 21 ± 18 g in the treated vs. control group, respectively, P = 0.64). Similar results were found when using creatine kinase and troponin I release, even after adjustment for the size of the AAR. This study shows that infarct size reduction by mechanical ischaemic PostC is lost when applied to patients with a TIMI 2-3 flow grade at admission. This indicates that the timing of the protective intervention with respect to the onset of reperfusion is a key factor for preventing lethal reperfusion injury in STEMI patients. NCT01483755. Published on behalf of the European

  1. Small acidic protein 1 and SCFTIR1 ubiquitin proteasome pathway act in concert to induce 2,4-dichlorophenoxyacetic acid-mediated alteration of actin in Arabidopsis roots.

    PubMed

    Takahashi, Maho; Umetsu, Kana; Oono, Yutaka; Higaki, Takumi; Blancaflor, Elison B; Rahman, Abidur

    2017-03-01

    2,4-Dichlorophenoxyacetic acid (2,4-D), a functional analogue of auxin, is used as an exogenous source of auxin as it evokes physiological responses like the endogenous auxin, indole-3-acetic acid (IAA). Previous molecular analyses of the auxin response pathway revealed that IAA and 2,4-D share a common mode of action to elicit downstream physiological responses. However, recent findings with 2,4-D-specific mutants suggested that 2,4-D and IAA might also use distinct pathways to modulate root growth in Arabidopsis. Using genetic and cellular approaches, we demonstrate that the distinct effects of 2,4-D and IAA on actin filament organization partly dictate the differential responses of roots to these two auxin analogues. 2,4-D but not IAA altered the actin structure in long-term and short-term assays. Analysis of the 2,4-D-specific mutant aar1-1 revealed that small acidic protein 1 (SMAP1) functions positively to facilitate the 2,4-D-induced depolymerization of actin. The ubiquitin proteasome mutants tir1-1 and axr1-12, which show enhanced resistance to 2,4-D compared with IAA for inhibition of root growth, were also found to have less disrupted actin filament networks after 2,4-D exposure. Consistently, a chemical inhibitor of the ubiquitin proteasome pathway mitigated the disrupting effects of 2,4-D on the organization of actin filaments. Roots of the double mutant aar1-1 tir1-1 also showed enhanced resistance to 2,4-D-induced inhibition of root growth and actin degradation compared with their respective parental lines. Collectively, these results suggest that the effects of 2,4-D on actin filament organization and root growth are mediated through synergistic interactions between SMAP1 and SCF TIR 1 ubiquitin proteasome components. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  2. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies.

    PubMed

    Taylor, Robert W; Pyle, Angela; Griffin, Helen; Blakely, Emma L; Duff, Jennifer; He, Langping; Smertenko, Tania; Alston, Charlotte L; Neeve, Vivienne C; Best, Andrew; Yarham, John W; Kirschner, Janbernd; Schara, Ulrike; Talim, Beril; Topaloglu, Haluk; Baric, Ivo; Holinski-Feder, Elke; Abicht, Angela; Czermin, Birgit; Kleinle, Stephanie; Morris, Andrew A M; Vassallo, Grace; Gorman, Grainne S; Ramesh, Venkateswaran; Turnbull, Douglass M; Santibanez-Koref, Mauro; McFarland, Robert; Horvath, Rita; Chinnery, Patrick F

    2014-07-02

    Mitochondrial disorders have emerged as a common cause of inherited disease, but their diagnosis remains challenging. Multiple respiratory chain complex defects are particularly difficult to diagnose at the molecular level because of the massive number of nuclear genes potentially involved in intramitochondrial protein synthesis, with many not yet linked to human disease. To determine the molecular basis of multiple respiratory chain complex deficiencies. We studied 53 patients referred to 2 national centers in the United Kingdom and Germany between 2005 and 2012. All had biochemical evidence of multiple respiratory chain complex defects but no primary pathogenic mitochondrial DNA mutation. Whole-exome sequencing was performed using 62-Mb exome enrichment, followed by variant prioritization using bioinformatic prediction tools, variant validation by Sanger sequencing, and segregation of the variant with the disease phenotype in the family. Presumptive causal variants were identified in 28 patients (53%; 95% CI, 39%-67%) and possible causal variants were identified in 4 (8%; 95% CI, 2%-18%). Together these accounted for 32 patients (60% 95% CI, 46%-74%) and involved 18 different genes. These included recurrent mutations in RMND1, AARS2, and MTO1, each on a haplotype background consistent with a shared founder allele, and potential novel mutations in 4 possible mitochondrial disease genes (VARS2, GARS, FLAD1, and PTCD1). Distinguishing clinical features included deafness and renal involvement associated with RMND1 and cardiomyopathy with AARS2 and MTO1. However, atypical clinical features were present in some patients, including normal liver function and Leigh syndrome (subacute necrotizing encephalomyelopathy) seen in association with TRMU mutations and no cardiomyopathy with founder SCO2 mutations. It was not possible to confidently identify the underlying genetic basis in 21 patients (40%; 95% CI, 26%-54%). Exome sequencing enhances the ability to identify

  3. The DarkSide direct dark matter search with liquid argon

    NASA Astrophysics Data System (ADS)

    Edkins, E.; Agnes, P.; Alexander, T.; Alton, A.; Arisaka, K.; Back, H. O.; Baldin, B.; Biery, K.; Bonfini, G.; Bossa, M.; Brigatti, A.; Brodsky, J.; Budano, F.; Cadonati, L.; Calaprice, F.; Canci, N.; Candela, A.; Cao, H.; Cariello, M.; Cavalcante, P.; Chavarria, A.; Chepurnov, A.; Cocco, A. G.; Crippa, L.; D'Angelo, D.; D'Incecco, M.; Davini, S.; De Deo, M.; Derbin, A.; Devoto, A.; Di Eusanio, F.; Di Pietro, G.; Empl, A.; Fan, A.; Fiorillo, G.; Fomenko, K.; Forster, G.; Franco, D.; Gabriele, F.; Galbiati, C.; Goretti, A.; Grandi, L.; Gromov, M.; Guan, M. Y.; Guardincerri, Y.; Hackett, B.; Herner, K.; Humble, P.; Hungerford, E. V.; Ianni, Al.; Ianni, An.; Jollet, C.; Keeter, K.; Kendziora, C.; Kobychev, V.; Koh, G.; Korablev, D.; Korga, G.; Kurlej, A.; Li, P. X.; Loer, B.; Lombardi, P.; Love, C.; Ludhova, L.; Luitz, S.; Ma, Y. Q.; Machulin, I.; Mandarano, A.; Mari, S.; Maricic, J.; Marini, L.; Martoff, C. J.; Meregaglia, A.; Meroni, E.; Meyers, P. D.; Milincic, R.; Montanari, D.; Montuschi, M.; Monzani, M. E.; Mosteiro, P.; Mount, B.; Muratova, V.; Musico, P.; Nelson, A.; Odrowski, S.; Okounkova, M.; Orsini, M.; Ortica, F.; Pagani, L.; Pallavicini, M.; Pantic, E.; Papp, L.; Parmeggiano, S.; Parsells, R.; Pelczar, K.; Pelliccia, N.; Perasso, S.; Pocar, A.; Pordes, S.; Pugachev, D.; Qian, H.; Randle, K.; Ranucci, G.; Razeto, A.; Reinhold, B.; Renshaw, A.; Romani, A.; Rossi, B.; Rossi, N.; Rountree, S. D.; Sablone, D.; Saggese, P.; Saldanha, R.; Sands, W.; Sangiorgio, S.; Segreto, E.; Semenov, D.; Shields, E.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Stanford, C.; Suvorov, Y.; Tartaglia, R.; Tatarowicz, J.; Testera, G.; Tonazzo, A.; Unzhakov, E.; Vogelaar, R. B.; Wada, M.; Walker, S.; Wang, H.; Wang, Y.; Watson, A.; Westerdale, S.; Wojcik, M.; Wright, A.; Xiang, X.; Xu, J.; Yang, C. G.; Yoo, J.; Zavatarelli, S.; Zec, A.; Zhu, C.; Zuzel, G.

    2017-11-01

    The DarkSide-50 direct dark matter detector is a liquid argon time projection chamber (TPC) surrounded by a liquid scintillator neutron veto (LSV) and a water Cerenkov muon veto (WCV). Located under 3800 m.w.e. at the Laboratori Nazionali del Gran Sasso, Italy, it is the only direct dark matter experiment currently operating background free. The atmospheric argon target was replaced with argon from underground sources in April, 2015. The level of 39Ar, a β emitter present in atmospheric argon (AAr), has been shown to have been reduced by a factor of (1.4 ± 0.2) x 103. The combined spin-independent WIMP exclusion limit of 2.0 x 10-44 cm2 (mχ = 100 GeV/c2) is currently the best limit on a liquid argon target.

  4. Frequencies, mechanisms and climate forcing of paleofloods in the Bernese Alps (Switzerland) inferred from natural, historical, and instrumental time series

    NASA Astrophysics Data System (ADS)

    Schulte, Lothar; Peña, Juan Carlos; Carvalho, Filipe; Julià, Ramon; Gómez-Bolea, Antonio; Burjachs, Francesc; Llorca, Jaime; Rubio, Patricio; Veit, Heinz

    2015-04-01

    The aim of this contribution is the reconstruction of a 2600-yr long flood series generated from high-resolution deltaplain sediments of the Hasli-Aare and Lütschine delta, which reproduces the fluvial dynamic and related mechanisms, including trends, clusters and gaps of floods in alpine catchments. Paleofloods frequencies were reconstructed from geoarchives particularly by sedimentary, geochemical (XRF-core scan, conventional XRF, LOI and grain size), mineralogical, geomorphological, pollen and lichenometric records. An important issue is the question if these paleofloods can be calibrated (exact dating) by data series from historical sources (textual and factual) and by instrumental data. Not less than 12 of 14 severe and catastrophic events before the termination of the River Aare Correction in 1867, are detected during the last 700 years also by coarse-grained flood layers, ln(Zr/Ti) peaks and Factor 1 scores. Spectral analysis of the geochemical and pollen time series and climate proxies (δ14C, TSI, δ18O isotopes from the Greenland ice, temperatures and precipitation reconstruction from tree-rings, NAO, SNAO) evidence similar periodicities of 60, 85, 105, 120 and 200 yrs during the two last Millennia. Thus, the mechanisms of the flood processes are strongly influenced by the North Atlantic dynamics and solar forcing. The composite 2600-yr sedimentary floodplain record illustrates that periods of organic soil formation and deposition of phyllosilicates (medium high catchment area) match very clearly to maxima of Total Solar Irradiance (Steinhilber et al., 2009) pointing to reduced flood activity during warmer climate pulses. The aggradation of the paleoflood clusters (e.g. 1300-1350, 1420-1480, 1550-1620, 1650-1720 and 1811-1851 cal yr AD) with contribution of siliciclasts from highest catchment area (plutonic bedrock) occurred predominantly during periods with cooler summer temperature, reduced solar irradiance and phases of drier spring climate (B

  5. Metasomatism in the Chain of Ponds K-feldspars: Reassessing Discrete Domain 39Ar-40Ar Modelling

    NASA Astrophysics Data System (ADS)

    Villa, I. M.; Chafe, A. N.; Hanchar, J. M.; Wirth, R.

    2012-12-01

    The post-crystallization petrology of K-feldspar (Kfs) is mostly controlled by fluids. Accordingly, [1] documented that successive mineral generations in Kfs grains of the Aar metagranite can be concordantly identified by both cathodoluminescence (CL) and back-scattered electron (BSE) imaging, elemental, and multi-isotope techniques. Imaging microstructures is a particularly powerful tool appreciated by many U-Pb geochronologists, and its use in 39Ar-40Ar dating is beginning to show beneficial progress [2]. However, a dissenting reviewer of [1] argued that the Aar sample was not typical of "orthodox" Kfs and the results could not be generalized to all Kfs [3]. On a different front, [4] demonstrated that the mathematical modeling that assumed Fickian diffusion in discrete domains, defined once and for all by [5], lacked internal consistency on several counts. As Chain of Ponds Pluton (CPP) Kfs sample MH-10 played a foundational role in the development of the mathematical model by [5], we decided to obtain direct evidence whether the numerous internal inconsistencies of the model are due to the previously undescribed petrological history of MH-10. We collected sample JH-02-01 on the same CPP outcrop as MH-10 [6]. All age spectra of different sieve fractions of the Kfs separate, both handpicked and unpicked, show a staircase shape. The Arrhenius diagram of apparent diffusivity agrees with the original MH-10 [5] and shows the same apparent r/r0 behavior. However, Arrhenius trajectories for all size fractions are parallel to each other and self-similar, as predicted by [4], instead of being joined at low temperature ("small domains") and diverging only at high T ("largest domain"), as would be implicit in the model by [5]. The CL and BSE images demonstrate several successive Kfs generations of diverse luminescence and chemical and isotopic properties. Microchemical analyses document patchy Ba enrichment, a tell-tale fingerprint of deuteric fluid interaction and

  6. Consensus recommendations from the American acne & rosacea society on the management of rosacea, part 4: a status report on physical modalities and devices.

    PubMed

    Tanghetti, Emil; Del Rosso, James Q; Thiboutot, Diane; Gallo, Richard; Webster, Guy; Eichenfield, Lawrence F; Stein-Gold, Linda; Berson, Diane; Zaenglein, Andrea

    2014-02-01

    The fourth article in this 5-part series reviews physical modalities and devices used to treat cutaneous rosacea based on consensus recommendations from the American Acne & Rosacea Society (AARS) on the management of the common presentations of cutaneous rosacea. The major therapeutic uses of physical modalities and devices, especially laser and light-based systems, are for treatment of telangiectases and persistent facial erythema (background erythema). Phymas, especially rhinophyma, also are treated with physical modalities such as ablative lasers or surgical devices (eg, electrosurgical loop). Appropriately selected and properly used lasers and intense pulsed light (IPL) devices can successfully address specific clinical manifestations of rosacea that exhibit limited or no response to available medical therapies, such as telangiectases and background centrofacial erythema. Rosacea-associated symptoms also may improve. In most cases, treatment will need to be repeated intermittently to sustain improvement.

  7. Anal carcinoma and HIV infection: is it time for screening?

    PubMed

    Herranz-Pinto, P; Sendagorta-Cudós, E; Bernardino-de la Serna, J I; Peña-Sánchez de Rivera, J M

    2014-03-01

    A 38-year-old white man had a 10-year history of human immunodeficiency virus (HIV) infection (A3), with no episodes of opportunistic diseases and in good immunologic recovery (CD4 cell count: 450 and indetectable HIV viral load) while on HAART. He presented with a two-month history of mild anal symptoms, including pruritus and episodic bleeding. He referred past episodes of anal warts, self-treated with several topical compounds, all proven unsuccessful. Perianal examination showed erythema and scratching. A 0.5cm sized tumor, with infiltration at the base was detected on digital exam, located at 15mm from the anal margin. Local biopsy driven by high-resolution anuscopy (AAR) yielded a final diagnosis of infiltrative epidermoid carcinoma. Might that neoplasia have been prevented? Copyright © 2013 Elsevier España, S.L. All rights reserved.

  8. Estimating the mutual information of an EEG-based Brain-Computer Interface.

    PubMed

    Schlögl, A; Neuper, C; Pfurtscheller, G

    2002-01-01

    An EEG-based Brain-Computer Interface (BCI) could be used as an additional communication channel between human thoughts and the environment. The efficacy of such a BCI depends mainly on the transmitted information rate. Shannon's communication theory was used to quantify the information rate of BCI data. For this purpose, experimental EEG data from four BCI experiments was analyzed off-line. Subjects imaginated left and right hand movements during EEG recording from the sensorimotor area. Adaptive autoregressive (AAR) parameters were used as features of single trial EEG and classified with linear discriminant analysis. The intra-trial variation as well as the inter-trial variability, the signal-to-noise ratio, the entropy of information, and the information rate were estimated. The entropy difference was used as a measure of the separability of two classes of EEG patterns.

  9. Time Trends in Breast Cancer Among Indian Women Population: An Analysis of Population Based Cancer Registry Data.

    PubMed

    Chaturvedi, Meesha; Vaitheeswaran, K; Satishkumar, K; Das, Priyanka; Stephen, S; Nandakumar, A

    2015-12-01

    The trends observed in cancer breast among Indian women are an indication of effect of changing lifestyle in population. To draw an appropriate inference regarding the trends of a particular type of cancer in a country, it is imperative to glance at the reliable data collected by Population Based Cancer Registries over a period of time. To give an insight of changing trends of breast cancer which have taken place over a period of time among women in Cancer Registries of India. Breast Cancer trends for invasive breast cancer in women in Indian Registries have varied during the selected period. Occurrence of breast cancers has also shown geographical variation in India. This data was collected by means of a 'Standard Core Proforma' designed by NCRP conforming to the data fields as suggested by International norms. The Proforma was filled by trained Registry workers based on interview/ hospital medical records/ supplementing data by inputs from treating surgeons/radiation oncologists/involved physicians/pathologists. The contents of the Proforma are entered into specifically created software and transmitted electronically to the coordinating center at Bangalore. The registries contributing to more number of years of data are called as older registries, while other recently established registries are called newer registries. While there has been an increase recorded in breast cancer in most of the registries, some of them have recorded an insignificant increase. Comparison of Age Adjusted Rates (AARs) among Indian Registries has been carried out after which trends observed in populations covered by Indian Registries are depicted. A variation in broad age groups of females and the proneness of females developing breast cancer over the period 1982 to 2010 has been shown. Comparisons of Indian registries with International counterparts have also been carried out. There are marked changes in incidence rates of cancer breast which have occurred in respective registries in a

  10. On the age of the penultimate full glaciation of New England

    USGS Publications Warehouse

    Oldale, R.N.; Colman, S.M.

    1992-01-01

    Tills that discontinuously underlie the late Wisconsinan till throughout New England represent the penultimate full glaciation of the region. In southern New England, the late Wisconsinan till and the tills that locally underlie it are informally referred to as upper and lower tills, respectively. For the most part, the ages of the lower tills are not firmly established, and regional correlations between occurrences of lower till, including those on Long Island, New York, are tenuous. Where a lower till underlies deposits having limiting middle Wisconsinan radiocarbon ages (e.g., the Montauk till member of the Manhassett Formation on Long Island at Port Washington, New York, and the lower till at New Sharon, Maine), many workers have assigned the till an early Wisconsinan age. However, lower tills throughout much of New England may be Illinoian or older in age and may correlate with a lower till exposed at Sankaty Head, Nantucket Island, Massachusetts, that is pre-Sangamonian in age. The till at Sankaty Head lies below marine beds containing marine faunas indicative of sea-water temperatures both warmer and slightly cooler than those off Nantucket today and that have uranium-thorium and amino-acid racemization (AAR) age estimates suggesting a Sangamonian age (marine oxygen-isotope stage 5).The lower till at Sankaty Head and the Montauk till member on Long Island were deposited during a full glaciation of New England that was at least as extensive as the late Wisconsinan advance of the Laurentide ice. Global ice-volume data from the marine oxygen-isotope record and the late Pleistocene eustatic sea-level record inferred from raised coral terraces support an advance of this magnitude during marine oxygenisotope stage 6, but not during stage 4.An early Wisconsinan age of the southern New England lower tills and, hence, of the penultimate glaciation there is problematic in terms of the pre-Sangamonian age of the lower till on Nantucket, and in terms of the late

  11. Reconstructed glacier geometry and inferred Equilibrium Line Altitude changes during the Late Pleistocene deglaciation in the Retezat Mountains, Southern Carpathians

    NASA Astrophysics Data System (ADS)

    Madarász, Balázs; Ruszkiczay-Rüdiger, Zsófia; Kern, Zoltán; Urdea, Petru

    2016-04-01

    Quaternary glaciations had a major imprint on the landscape and topography of the Southern Carpathians. Their transitional position between continental and Mediterranean climate zones arouses special interest concerning the timing and pattern of glaciations in this area. Probably the Retezat Mts hosted the most extended glaciation during the Late Pleistocene within this range. The peak elevations of the study area reach 2500 m asl, and the most extended glaciers descended to 1040 m in the northern and to 1130 m on the southern valleys. Major cirque floors are typically situated at 2000-2100 m asl. Glacial landforms have been mapped in order to reconstruct the past ice bodies and the elevation shifts of the paleo equilibrium line altitudes (ELA) during several deglaciation phases of the Last Glacial Maximum (LGM) and Lateglacial in the Retezat Mts. On the basis of published 10Be exposure age data on the northern valleys of the study area, deglaciation of the Retezat Mts occurred at least in five phases between ~21.0 ka and 13.5 ka [1]. Various methods (THAR, AAR, AABR) have been tested using a GIS tool to estimate the ELA of the reconstructed paleoglaciers [2] and paleo ELAs were calculated for each of the deglaciation phases. Preliminary estimates of regional LGM paleoELA employing the simplest THAR method (with a ratio of 0.5) ranged from ~1670 m during the LGM to ~2210 m for the smallest cirque glacier at 13.5 ka, respectively. The AAR and AABR methods provide somewhat higher ELAs for each phase. The obtained paleoELAs were compared to ELA reconstructions available from other Carpathian ranges and also to the Alps and Dinarides. Our data will contribute to a more accurate ELA distribution during the LGM, which may be indicative of the past state of the climate system (moisture gradient, circulation regimes). Thanks to OTKA PD83610, PD104899; NKM-96/2014, NKM-31/2015; OMAA 90öu17; LP2012-27/2012. References: [1] Ruszkiczay-Rüdiger et al. 2016 Quat. Int. (in

  12. Characterization of cDNAs and genomic DNAs for human threonyl- and cysteinyl-tRNA synthetases

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

    Cruzen, M.E.

    1993-01-01

    Techniques of molecular biology were used to clone, sequence and map two human aminoacyl-tRNA synthetase (aaRS) cDNAs: threonyl-tRNA synthetase (ThrRS) a class II enzyme and cysteinyl-tRNA synthetase (CysRS) a class I enzyme. The predicted protein sequence of human ThrRS is highly homologous to that of lower eukaryotic and prokaryotic ThRSs, particularly in the regions containing the three structural motifs common to all class II synthetases. Signature regions 1 and 2, which characterize the class IIa subgroup (SerRS, ThrRS and HisRS) are highly conserved from bacteria to human. Structural predictions for human ThrRS based on the known structure of the closelymore » related SerRS from E.coli implicate strongly conserved residues in the signature sequences to be important in substrate binding. The amino terminal 100 residues of the deduced amino acid sequence of ThrRS shares structural similarity to SerRS consistent with forming an antiparallel helix implicated in tRNA binding. The 5' untranslated sequence of the human ThrRS gene shares short stretches of common sequence with the gene for hamster HisRS including a binding site for the promoter specific transcription factor sp-1. The deduced amino acid sequence of human CysRS has a high degree of sequence identify to E. coli CysRS. Human CysRS possesses the classic characteristics of a class I synthetase and is most closely related to the MetRS subgroup. The amino terminal half of human CysRS can be modeled as a nucleotide binding fold and shares significant sequence and structural similarity to the other enzymes in this subgroup. The CysRS structural gene (CARS) was mapped to human chromosome 11p15.5 by fluorescent in situ hybridization. CARS is the first aaRS gene to be mapped to chromosome 11. The steady state of both CysRS and ThrRs mRNA were quantitated in several human tissues. Message levels for these enzymes appear to be subjected to differential regulation in different cell types.« less

  13. Babies Living Safe & Smokefree: randomized controlled trial of a multilevel multimodal behavioral intervention to reduce low-income children's tobacco smoke exposure.

    PubMed

    Collins, Bradley N; Lepore, Stephen J

    2017-03-14

    Addressing children's tobacco smoke exposure (TSE) remains a public health priority. However, there is low uptake and ineffectiveness of treatment, particularly in low-income populations that face numerous challenges to smoking behavior change. A multilevel intervention combining system-level health messaging and advice about TSE delivered at community clinics that disseminate the Special Supplemental Nutrition Program for Women, Infants and Children (WIC), combined with nicotine replacement and intensive multimodal, individual-level behavioral intervention may improve TSE control efforts in such high-risk populations. This trial uses a randomized two-group design with three measurement points: baseline, 3-month and 12-month follow-up. The primary outcome is bioverified child TSE; the secondary outcome is bioverified maternal quit status. Smoking mothers of children less than 6 years old are recruited from WIC clinics. All participants receive WIC system-level intervention based on the "Ask, Advise, Refer (AAR)" best practices guidelines for pediatrics clinics. It includes training all WIC staff about the importance of maternal tobacco control; and detailing clinics with AAR intervention prompts in routine work flow to remind WIC nutrition counselors to ask all mothers about child TSE, advise about TSE harms and benefits of protection, and refer smokers to cessation services. After receiving the system intervention, mothers are randomized to receive 3 months of additional treatment or an attention control intervention: (1) The multimodal behavioral intervention (MBI) treatment includes telephone counseling sessions about child TSE reduction and smoking cessation, provision of nicotine replacement therapy, a mobile app to support cessation efforts, and multimedia text messages about TSE and smoking cessation; (2) The attention control intervention offers equivalent contact as the MBI and includes nutrition-focused telephone counseling, mobile app, and multimedia

  14. Fuzzy object modeling

    NASA Astrophysics Data System (ADS)

    Udupa, Jayaram K.; Odhner, Dewey; Falcao, Alexandre X.; Ciesielski, Krzysztof C.; Miranda, Paulo A. V.; Vaideeswaran, Pavithra; Mishra, Shipra; Grevera, George J.; Saboury, Babak; Torigian, Drew A.

    2011-03-01

    To make Quantitative Radiology (QR) a reality in routine clinical practice, computerized automatic anatomy recognition (AAR) becomes essential. As part of this larger goal, we present in this paper a novel fuzzy strategy for building bodywide group-wise anatomic models. They have the potential to handle uncertainties and variability in anatomy naturally and to be integrated with the fuzzy connectedness framework for image segmentation. Our approach is to build a family of models, called the Virtual Quantitative Human, representing normal adult subjects at a chosen resolution of the population variables (gender, age). Models are represented hierarchically, the descendents representing organs contained in parent organs. Based on an index of fuzziness of the models, 32 thorax data sets, and 10 organs defined in them, we found that the hierarchical approach to modeling can effectively handle the non-linear relationships in position, scale, and orientation that exist among organs in different patients.

  15. Peripatetic Highlights in Bern

    NASA Astrophysics Data System (ADS)

    Hentschel, Ann M.

    The capital city of the Swiss Canton of Bern and of the Swiss Confederation is nestled in a narrow loop of the Aare river, at the foot of the Alps. The old town, founded around 1191, is well preserved despite a devastating fire in 1405.** Major industries of the region developed under the constraints of modest domestic markets, high transportation costs, and protectionist legislation across national borders. Switzerland thus found its niche in higher-end markets, such as chocolate making, engine building, instruments, fine textiles, and chemicals or pharmaceuticals. My tour past historically significant scientific sites in Bern will use the local legacy of its most illustrious residents, Albert Einstein (1879-1955), who lived there from 1902-1909, and Fritz Houtermans (1903-1966), who lived there from 1952-1966, as its guiding thread through the old town and the university district. Place names in italics mark stops along the tour.

  16. A Modified Double Multiple Nonlinear Regression Constitutive Equation for Modeling and Prediction of High Temperature Flow Behavior of BFe10-1-2 Alloy

    NASA Astrophysics Data System (ADS)

    Cai, Jun; Wang, Kuaishe; Shi, Jiamin; Wang, Wen; Liu, Yingying

    2018-01-01

    Constitutive analysis for hot working of BFe10-1-2 alloy was carried out by using experimental stress-strain data from isothermal hot compression tests, in a wide range of temperature of 1,023 1,273 K, and strain rate range of 0.001 10 s-1. A constitutive equation based on modified double multiple nonlinear regression was proposed considering the independent effects of strain, strain rate, temperature and their interrelation. The predicted flow stress data calculated from the developed equation was compared with the experimental data. Correlation coefficient (R), average absolute relative error (AARE) and relative errors were introduced to verify the validity of the developed constitutive equation. Subsequently, a comparative study was made on the capability of strain-compensated Arrhenius-type constitutive model. The results showed that the developed constitutive equation based on modified double multiple nonlinear regression could predict flow stress of BFe10-1-2 alloy with good correlation and generalization.

  17. Design Considerations of ISTAR Hydrocarbon Fueled Combustor Operating in Air Augmented Rocket, Ramjet and Scramjet Modes

    NASA Technical Reports Server (NTRS)

    Andreadis, Dean; Drake, Alan; Garrett, Joseph L.; Gettinger, Christopher D.; Hoxie, Stephen S.

    2003-01-01

    The development and ground test of a rocket-based combined cycle (RBCC) propulsion system is being conducted as part of the NASA Marshall Space Flight Center (MSFC) Integrated System Test of an Airbreathing Rocket (ISTAR) program. The eventual flight vehicle (X-43B) is designed to support an air-launched self-powered Mach 0.7 to 7.0 demonstration of an RBCC engine through all of its airbreathing propulsion modes - air augmented rocket (AAR), ramjet (RJ), and scramjet (SJ). Through the use of analytical tools, numerical simulations, and experimental tests the ISTAR program is developing and validating a hydrocarbon-fueled RBCC combustor design methodology. This methodology will then be used to design an integrated RBCC propulsion system that produces robust ignition and combustion stability characteristics while maximizing combustion efficiency and minimizing drag losses. First order analytical and numerical methods used to design hydrocarbon-fueled combustors are discussed with emphasis on the methods and determination of requirements necessary to establish engine operability and performance characteristics.

  18. Design Considerations of Istar Hydrocarbon Fueled Combustor Operating in Air Augmented Rocket, Ramjet and Scramjet Modes

    NASA Technical Reports Server (NTRS)

    Andreadis, Dean; Drake, Alan; Garrett, Joseph L.; Gettinger, Christopher D.; Hoxie, Stephen S.

    2002-01-01

    The development and ground test of a rocket-based combined cycle (RBCC) propulsion system is being conducted as part of the NASA Marshall Space Flight Center (MSFC) Integrated System Test of an Airbreathing Rocket (ISTAR) program. The eventual flight vehicle (X-43B) is designed to support an air-launched self-powered Mach 0.7 to 7.0 demonstration of an RBCC engine through all of its airbreathing propulsion modes - air augmented rocket (AAR), ramjet (RJ), and scramjet (SJ). Through the use of analytical tools, numerical simulations, and experimental tests the ISTAR program is developing and validating a hydrocarbon-fueled RBCC combustor design methodology. This methodology will then be used to design an integrated RBCC propulsion system thai: produces robust ignition and combustion stability characteristics while maximizing combustion efficiency and minimizing drag losses. First order analytical and numerical methods used to design hydrocarbon-fueled combustors are discussed with emphasis on the methods and determination of requirements necessary to establish engine operability and performance characteristics.

  19. Transfer Relations Between Landscape Functions - The Hydrological Point of View

    NASA Astrophysics Data System (ADS)

    Fohrer, N.; Lenhart, T.; Eckhardt, K.; Frede, H.-G.

    EC market policies and regional subsidy programs have an enormous impact on local land use. This has far reaching consequences on various landscape functions. In the joint research project SFB299 at the Giessen University the effect of land use options on economic, ecological and hydrological landscape functions are under investigation. The continuous time step model SWAT-G (Eckhardt et al., 2000; Arnold et al., 1998) is employed to characterize the influence of land use patterns on hydrological processes. The model was calibrated and validated employing a split sample approach. For two mesoscale watersheds (Aar, 60 km2; Dietzhölze, 81 km2) located in the Lahn-Dill- Bergland, Germany, different land use scenarios were analyzed with regard to their hydrological impact. Additionally the effect of land use change was analyzed with an ecological and an agro-economic model. The impact of the stepwise changing land use was expressed as trade off relations between different landscape functions.

  20. Tailed giant Tupanvirus possesses the most complete translational apparatus of the known virosphere.

    PubMed

    Abrahão, Jônatas; Silva, Lorena; Silva, Ludmila Santos; Khalil, Jacques Yaacoub Bou; Rodrigues, Rodrigo; Arantes, Thalita; Assis, Felipe; Boratto, Paulo; Andrade, Miguel; Kroon, Erna Geessien; Ribeiro, Bergmann; Bergier, Ivan; Seligmann, Herve; Ghigo, Eric; Colson, Philippe; Levasseur, Anthony; Kroemer, Guido; Raoult, Didier; La Scola, Bernard

    2018-02-27

    Here we report the discovery of two Tupanvirus strains, the longest tailed Mimiviridae members isolated in amoebae. Their genomes are 1.44-1.51 Mb linear double-strand DNA coding for 1276-1425 predicted proteins. Tupanviruses share the same ancestors with mimivirus lineages and these giant viruses present the largest translational apparatus within the known virosphere, with up to 70 tRNA, 20 aaRS, 11 factors for all translation steps, and factors related to tRNA/mRNA maturation and ribosome protein modification. Moreover, two sequences with significant similarity to intronic regions of 18 S rRNA genes are encoded by the tupanviruses and highly expressed. In this translation-associated gene set, only the ribosome is lacking. At high multiplicity of infections, tupanvirus is also cytotoxic and causes a severe shutdown of ribosomal RNA and a progressive degradation of the nucleus in host and non-host cells. The analysis of tupanviruses constitutes a new step toward understanding the evolution of giant viruses.

  1. Prediction of Weather Impacted Airport Capacity using Ensemble Learning

    NASA Technical Reports Server (NTRS)

    Wang, Yao Xun

    2011-01-01

    Ensemble learning with the Bagging Decision Tree (BDT) model was used to assess the impact of weather on airport capacities at selected high-demand airports in the United States. The ensemble bagging decision tree models were developed and validated using the Federal Aviation Administration (FAA) Aviation System Performance Metrics (ASPM) data and weather forecast at these airports. The study examines the performance of BDT, along with traditional single Support Vector Machines (SVM), for airport runway configuration selection and airport arrival rates (AAR) prediction during weather impacts. Testing of these models was accomplished using observed weather, weather forecast, and airport operation information at the chosen airports. The experimental results show that ensemble methods are more accurate than a single SVM classifier. The airport capacity ensemble method presented here can be used as a decision support model that supports air traffic flow management to meet the weather impacted airport capacity in order to reduce costs and increase safety.

  2. Late Holocene climate change at Goat Lake, Kenai Mountains, south-central Alaska

    NASA Astrophysics Data System (ADS)

    Daigle, T. A.; Kaufman, D. S.

    2006-12-01

    Lake sediments, glacier extents, and tree rings were used to reconstruct late Holocene climate changes from Goat Lake in the Kenai Mountains, south-central Alaska (60° 14' N/149° 54' W). Two sediment cores (3.7 and 5.6 m long) were dated with 16 AMS 14C ages and record changes in watershed (organic- matter content) and within-lake (biogenic silica) productivity since ~9500 cal yr BP. Sediment analyses focused on the last 1000 yr; this interval includes a sharp transition from gyttja to inorganic mud at ~1660 AD, which marks the fist time since Pleistocene deglaciation that the north goat outlet glacier (NGO) of the Harding Icefield overtopped the drainage divide at 590 m asl to spill meltwater into Goat Lake. One 14C age of ~1535 AD from a subfossil log in the NGO valley requires ~125 yr for the NGO to thicken 150 m to the elevation of the drainage divide where it remained until ~1930. Since ~1930, the NGO has thinned 150 m and retreated 1.4 km. Equilibrium-line altitudes (ELA) were reconstructed for 12 cirque glaciers nearby Goat Lake based on the accumulation-area ratio (AAR) method following field mapping of ice-marginal features formed during the maximum Little Ice Age (LIA) in the 19th century. Maximum LIA ELA data (AAR = 0.58) were compared with 1950 ELA and yield an average lowering of 50 ± 20 m. Application of the local lapse rate of 0.47°C/100 m indicates an average ablation-season temperature reduction of 0.3°C during the maximum LIA compared to 1950, assuming no change in winter precipitation. A new tree-ring chronology from 27 hemlock trees in the Goat Lake watershed correlates with mean March through August temperature from Kenai airport (r = 0.35) and a 207 yr reconstruction indicates an average temperature reduction of 1.0°C from 1800-1900 compared with 1930-1950. Assuming no change in winter precipitation, then a 1°C cooling should have been associated with an ELA lowering by 200 m. This did not occur, and we suggest that some degree of

  3. Medicinal chemistry of adenosine, P2Y and P2X receptors.

    PubMed

    Jacobson, Kenneth A; Müller, Christa E

    2016-05-01

    Pharmacological tool compounds are now available to define action at the adenosine (ARs), P2Y and P2X receptors. We present a selection of the most commonly used agents to study purines in the nervous system. Some of these compounds, including A1 and A3 AR agonists, P2Y1R and P2Y12R antagonists, and P2X3, P2X4 and P2X7 antagonists, are potentially of clinical use in treatment of disorders of the nervous system, such as chronic pain, neurodegeneration and brain injury. Agonists of the A2AAR and P2Y2R are already used clinically, P2Y12R antagonists are widely used antithrombotics and an antagonist of the A2AAR is approved in Japan for treating Parkinson's disease. The selectivity defined for some of the previously introduced compounds has been revised with updated pharmacological characterization, for example, various AR agonists and antagonists were deemed A1AR or A3AR selective based on human data, but species differences indicated a reduction in selectivity ratios in other species. Also, many of the P2R ligands still lack bioavailability due to charged groups or hydrolytic (either enzymatic or chemical) instability. X-ray crystallographic structures of AR and P2YRs have shifted the mode of ligand discovery to structure-based approaches rather than previous empirical approaches. The X-ray structures can be utilized either for in silico screening of chemically diverse libraries for the discovery of novel ligands or for enhancement of the properties of known ligands by chemical modification. Although X-ray structures of the zebrafish P2X4R have been reported, there is scant structural information about ligand recognition in these trimeric ion channels. In summary, there are definitive, selective agonists and antagonists for all of the ARs and some of the P2YRs; while the pharmacochemistry of P2XRs is still in nascent stages. The therapeutic potential of selectively modulating these receptors is continuing to gain interest in such fields as cancer, inflammation, pain

  4. Monitoring temporal variations in water resources across the Arabian Peninsula and identification of their controlling factors

    NASA Astrophysics Data System (ADS)

    Ahmed, M.; Sultan, M.; Othman, A.

    2015-12-01

    Assessment, monitoring, and development of the fresh water resources in the Arabian Peninsula (AP) are critical for the sustenance of the AP's growing population and water consumption. Monthly (01/2003-12/2013) Gravity Recovery and Climate Experiment (GRACE) data along with other relevant climatic, geologic, hydrogeologic, and remote sensing datasets were used to monitor the spatiotemporal variability in the AP's water resources and to investigate the causes of those variations. Four regions were selected; in our selection, we tried to cover major aquifers, follow political boundaries, and exceed GRACE footprint (~0.20×106 km2) to minimize uncertainties. The selected regions are: (1) Northern Saudi Arabia and Jordan (area: 0.53×106 km2), (2) Southern Saudi Arabia, Qatar and United Arab Emiratis (area: 0.97×106 km2), (3) Yemen (area: 0.45×106 km2), and (4) Oman (area: 0.32×106 km2). Results indicate: (1) Northern Saudi Arabia and Jordan area is experiencing large depletions (-8.76±0.94 mm/yr; -4.68±0.50 km3/yr) in GRACE-derived terrestrial water storage (TWS) that is largely related to groundwater extraction as well as decrease in rainfall rates throughout the investigated period compared to the preceding period (average annual rainfall [AAR]: 2003-2013: 58 mm; 1979-2002: 103 mm), (2) Southern Saudi Arabia, Qatar and United Arab Emiratis area is experiencing a moderate depletion (-2.73±1.0 mm/yr; -2.63±0.96 km3/yr) in TWS that might be related to groundwater/oil extraction as well as a moderate decrease in rainfall rates (AAR: 2003-2013: 61 mm; 1979-2002: 82 mm), (3) Yemen is experiencing a slight depletion (-0.82±0.30 mm/yr; -0.36±0.13 km3/yr) in TWS that might be related groundwater extraction, and (4) Oman is experiencing slight increase (+0.78±0.30 mm/yr; +0.25±0.09 km3/yr) in TWS that might be related an increase in rainfall rates. Our preliminary results are being further examined by: (1) extracting temporal variations in groundwater storage by

  5. Fracture distribution and porosity in a fault-bound hydrothermal system (Grimsel Pass, Swiss Alps)

    NASA Astrophysics Data System (ADS)

    Egli, Daniel; Küng, Sulamith; Baumann, Rahel; Berger, Alfons; Baron, Ludovic; Herwegh, Marco

    2017-04-01

    The spatial distribution, orientation and continuity of brittle and ductile structures strongly control fluid pathways in a rock mass by joining existing pores and creating new pore space (fractures, joints) but can also act as seals to fluid flow (e.g. ductile shear zones, clay-rich fault gouges). In long-lived hydrothermal systems, permeability and the related fluid flow paths are therefore dynamic in space and time. Understanding the evolution and behaviour of naturally porous and permeable rock masses is critical for the successful exploration and sustainable exploitation of hydrothermal systems and can advance methods for planning and implementation of enhanced geothermal systems. This study focuses on an active fault-bound hydrothermal system in the crystalline basement of the Aar Massif (hydrothermal field Grimsel Pass, Swiss Alps) that has been exhumed from few kilometres depth and which documents at least 3 Ma of hydrothermal activity. The explored rock unit of the Aar massif is part of the External Crystalline Massifs that hosts a multitude of thermal springs on its southern border in the Swiss Rhône valley and furthermore represents the exhumed equivalent of potentially exploitable geothermal reservoirs in the deep crystalline subsurface of the northern Alpine foreland basin. This study combines structural data collected from a 125 m long drillhole across the hydrothermal zone, the corresponding drill core and surface mapping. Different methods are applied to estimate the porosity and the structural evolution with regard to porosity, permeability and fracture distribution. Analyses are carried out from the micrometre to decametre scale with main focus on the flow path evolution with time. This includes a large variety of porosity-types including fracture-porosity with up to cm-sized aperture down to grain-scale porosity. Main rock types are granitoid host rocks, mylonites, paleo-breccia and recent breccias. The porosity of the host rock as well as the

  6. Aminostratigraphy of surface and subsurface Quaternary sediments, North Carolina coastal plain, USA

    USGS Publications Warehouse

    Wehmiller, John F.; Thieler, E. Robert; Miller, D.; Pellerito, V.; Bakeman, Keeney V.; Riggs, S.R.; Culver, S.; Mallinson, D.; Farrell, K.M.; York, L.L.; Pierson, J.; Parham, P.R.

    2010-01-01

    The Quaternary stratigraphy and geochronology of the Albemarle Embayment of the North Carolina (NC) Coastal Plain is examined using amino acid racemization (AAR) in marine mollusks, in combination with geophysical, lithologic, and biostratigraphic analysis of 28 rotasonic cores drilled between 2002 and 2006. The Albemarle Embayment is bounded by structural highs to the north and south, and Quaternary strata thin westward toward the Suffolk paleoshoreline, frequently referred to as the Suffolk Scarp. The Quaternary section is up to ∼90 m thick, consists of a variety of estuarine, shelf, back-barrier, and lagoonal deposits, and has been influenced by multiple sea-level cycles. The temporal resolution of the amino acid racemization method is tested statistically and with the stratigraphic control provided by this geologic framework, and it is then applied to the correlation and age estimation of subsurface units throughout the region. Over 500 specimens (primarily Mercenaria and Mulinia) from the subsurface section have been analyzed using either gas chromatographic (GC) or reverse-phase liquid chromatographic (RPLC) techniques. The subsurface stratigraphic data are compared with AAR results from numerous natural or excavated exposures from the surrounding region, as well as results from NC beach collections, to develop a comprehensive aminostratigraphic database for the entire Quaternary record within the NC coastal system. Age mixing, recognized in the beach collections, is also seen in subsurface sections, usually where major seismic reflections or core lithology indicate the presence of stratigraphic discontinuities. Kinetic models for racemization are tested within the regional stratigraphic framework, using either radiocarbon or U-series calibrations or comparison with regional biostratigraphy. Three major Pleistocene aminozones [AZ2, AZ3, and AZ4] are found throughout the region, all being found in superposition in several cores. Each can be subdivided

  7. Landscape History of Grosses Moos, NW Swiss Alpine Foreland.

    NASA Astrophysics Data System (ADS)

    Joanna Heer, Aleksandra; Adamiec, Grzegorz; Veit, Heinz; May, Jan-Hendrik; Novenko, Elena; Hajdas, Irka

    2017-04-01

    The western Swiss Plateau with Lake Neuchâtel is part of the alpine foreland and among the key areas for the reconstruction of environmental changes since the last postglacial. This study was carried out in a landscape located NE of the lake and called Grosses Moos (The Large Fen) - currently designated the Swiss largest, continuous farming area, after the fen was drained in course of landscape engineering projects performed in Switzerland at the end of the 19th century. The study contributes new results from nine excavations of littoral ridges identified in Grosses Moos, and integrates sedimentology, paleo-environmental analysis and three independent chronological methods. Radiocarbon dating, pollen analysis and optically stimulated luminescence (OSL) were applied to the sediments. While pollen and radiocarbon follow the standard procedures, the evaluation of the luminescence age estimates demanded adjustment according to the physical and microdosimetric properties of the alpine quartz, and consideration of the peculiarities of the changing littoral environments of Grosses Moos. The Grosses Moos landscape developed on the temporary surface of the post-Last Glacial sedimentary infill of the over-deepened glacial Aare valley. In this study the landscape history has been fitted into the existing supraregional time scales of NGRIP, the Swiss bio-zones system and the human history based on archaeological and historic records and covers a time span of up to 15'000 yr b2k. The wide-ranging suite of geomorphic features and sedimentary sequences, including littoral lake sediments, beach ridges, dunes, palaeo-channels, peat and colluvial deposits, enable the extensive reconstruction of spatially and temporally variable natural shaping processes. In addition, our results indicate remobilization of soil, colluvium, and sediment due to human settlement activities since the Neolithic - with an important increase in sediment load and spatial variability since the Bronze Age

  8. The history of Cesium-137 liquid emissions by Mühleberg Nuclear Power Plant (Switzerland) is recorded in Lake Biel sediments

    NASA Astrophysics Data System (ADS)

    Girardclos, Stéphanie; Faessler, Jérôme; Loizeau, Jean-Luc; Zehringer, Markus

    2014-05-01

    Lake sediments record changes happening in their upstream river catchment and regional environment which includes traces of artificial radionuclides emissions deriving from human activities. 137Cs emissions started worldwide in the early 1950's and peaked in 1963-64 due to nuclear bomb tests in the high atmosphere. A second 137Cs activity peak, due to the 1986 Chernobyl catastrophe is recorded in sediment archives from central Europe. These two events (1963/64 and 1986) serve routinely as time markers for recent lake records. Nuclear Power Plants (NPPs) are often constructed along river course for cooling purposes. Since 1972, Mühleberg NPP (central Switzerland) lies 18 km upstream Lake Biel and releases radioactive liquid emissions into the Aare river which adds to the diffuse - above mentioned - radioactive pollution, as revealed by Albrecht et al. (1995; 1998) and recently confirmed by Thevenon et al. (2013) from Lake Biel sediments. The water of Lake Biel is used as drinking water for ca. 60'000 inhabitants and its outflowing water is further used by downstream cities lying on the Aare-Rhine course such as Basel (200'000 inhab.) In this study, the 137Cs activity curve of a 90-cm-long sediment core (BIE10-8), retrieved in April 2010 from the central Lake Biel basin at ca. 50 m depth, and measured by gamma ray spectrometry using high resolution germanium detectors, confirms previous work and reveals a new peak for the year 1998-2000, as observed by Thevenon et al. (2013). This peak is most certainly due to Mühleberg NPP as shown by the good correlation with declared 137Cs liquid emissions indicating a significant increase in 1998-99. Decay corrected activity data, converted into 137Cs fluxes, point to water pollution by Mühleberg NPP in 1975-1985 as being similar to those linked to the catastrophic events in 1963-64 and 1986 (about 75%). As former study showed that Lake Biel sediments scavenge only a portion of the total radionuclide in water, i.e. 30-55% for

  9. Regulation of G-protein coupled receptor traffic by an evolutionary conserved hydrophobic signal.

    PubMed

    Angelotti, Tim; Daunt, David; Shcherbakova, Olga G; Kobilka, Brian; Hurt, Carl M

    2010-04-01

    Plasma membrane (PM) expression of G-protein coupled receptors (GPCRs) is required for activation by extracellular ligands; however, mechanisms that regulate PM expression of GPCRs are poorly understood. For some GPCRs, such as alpha2c-adrenergic receptors (alpha(2c)-ARs), heterologous expression in non-native cells results in limited PM expression and extensive endoplasmic reticulum (ER) retention. Recently, ER export/retentions signals have been proposed to regulate cellular trafficking of several GPCRs. By utilizing a chimeric alpha(2a)/alpha(2c)-AR strategy, we identified an evolutionary conserved hydrophobic sequence (ALAAALAAAAA) in the extracellular amino terminal region that is responsible in part for alpha(2c)-AR subtype-specific trafficking. To our knowledge, this is the first luminal ER retention signal reported for a GPCR. Removal or disruption of the ER retention signal dramatically increased PM expression and decreased ER retention. Conversely, transplantation of this hydrophobic sequence into alpha(2a)-ARs reduced their PM expression and increased ER retention. This evolutionary conserved hydrophobic trafficking signal within alpha(2c)-ARs serves as a regulator of GPCR trafficking.

  10. Millennial-scale climate variations in western Mediterranean during late Pleistocene-early Holocene: multi-proxy analyses from Padul peatbog (southern Iberian Peninsula)

    NASA Astrophysics Data System (ADS)

    Camuera, Jon; Jiménez-Moreno, Gonzalo; José Ramos-Román, María; García-Alix, Antonio; Jiménez-Espejo, Francisco; Toney, Jaime L.; Anderson, R. Scott; Kaufman, Darrell; Bright, Jordon; Sachse, Dirk

    2017-04-01

    Padul peatbog, located in southern Iberian Peninsula (western Mediterranean region) is a unique area for palaeoenvironmental studies due to its location, between arid and temperate climates. Previous studies showed that the Padul peatbog contains a continuous record of the last ca. 0.8-1 Ma, so it is an extraordinary site to identify glacial-interglacial phases as well as Heinrich and D-O events, linked to orbital- and suborbital-scale variations. In 2015, a new 42 m long core was taken from this area, providing an excellent sediment record probably for the last ca. 300,000 years. This study is focused on the paleoenvironmental and climatic reconstruction of the late Pleistocene and the early Holocene (ca. from 50,000 to 9,500 cal. yrs BP), using AMS 14C and AAR dating, high-resolution pollen analysis, lithology, continuous XRF-scanning, X-ray diffraction, magnetic susceptibility and organic geochemistry. These different proxies provide information not only about the regional environment change but also about local changes in the conditions of the Padul lake/peatbog due to variations in water temperature, pH or nutrients.

  11. Glaciological and hydrological sensitivities in the Hindu Kush - Himalaya

    NASA Astrophysics Data System (ADS)

    Shea, Joseph; Immerzeel, Walter

    2016-04-01

    Glacier responses to future climate change will affect hydrology at subbasin-scales. The main goal of this study is to assess glaciological and hydrological sensitivities of sub-basins throughout the Hindu Kush - Himalaya (HKH) region. We use a simple geometrical analysis based on a full glacier inventory and digital elevation model (DEM) to estimate sub-basin equilibrium line altitudes (ELA) from assumptions of steady-state accumulation area ratios (AARs). The ELA response to an increase in temperature is expressed as a function of mean annual precipitation, derived from a range of high-altitude studies. Changes in glacier contributions to streamflow in response to increased temperatures are examined for scenarios of both static and adjusted glacier geometries. On average, glacier contributions to streamflow increase by approximately 50% for a +1K warming based on a static geometry. Large decreases (-60% on average) occur in all basins when glacier geometries are instantaneously adjusted to reflect the new ELA. Finally, we provide estimates of sub-basin glacier response times that suggest a majority of basins will experience declining glacier contributions by the year 2100.

  12. Biscrolling nanotube sheets and functional guests into yarns

    NASA Astrophysics Data System (ADS)

    Baughman, Ray

    2011-03-01

    Multifunctional applications of textiles have been limited by the inability to spin important materials into yarns. Generically applicable methods are demonstrated for producing weavable yarns comprising up to 95 wt % of otherwise unspinnable particulate or nanofiber powders that remain highly functional. Scrolled 50 nm thick carbon nanotube sheets confine these powders in the galleries of irregular scroll sacks, whose observed complex structures are related to twist-dependent extension of Archimedean spirals, Fermat spirals, or spiral pairs into scrolls. The strength and electronic connectivity of a small weight fraction of scrolled carbon nanotube sheet enables yarn weaving, sewing, knotting, braiding, and charge collection. This technology is used to make yarns of superconductors, Li-ion battery materials, graphene ribbons, catalytic nanofibers for fuel cells, and Ti O2 for photocatalysis. Work done in collaboration with Shaoli Fang, Xavier Lepro-Chavez, Chihye Lewis, Raquel Ovalle-Robles, Javier Carratero-Gonzalez, Elisabet Castillo-Martinez, Mikhail Kozlov, Jiyoung Oh, Neema Rawat, Carter Haines, Mohammed Haque, Vaishnavi Aare, Stephanie Stoughton, Anvar Zakhidov, and Ray Baughman, The University of Texas at Dallas / Alan G. MacDiarmid NanoTech Institute.

  13. Analysis of RNA structure using small-angle X-ray scattering

    PubMed Central

    Cantara, William A.; Olson, Erik D.; Musier-Forsyth, Karin

    2016-01-01

    In addition to their role in correctly attaching specific amino acids to cognate tRNAs, aminoacyl-tRNA synthetases (aaRS) have been found to possess many alternative functions and often bind to and act on other nucleic acids. In contrast to the well-defined 3D structure of tRNA, the structures of many of the other RNAs recognized by aaRSs have not been solved. Despite advances in the use of X-ray crystallography (XRC), nuclear magnetic resonance (NMR) spectroscopy and cryo-electron microscopy (cryo-EM) for structural characterization of biomolecules, significant challenges to solving RNA structures still exist. Recently, small-angle X-ray scattering (SAXS) has been increasingly employed to characterize the 3D structures of RNAs and RNA-protein complexes. SAXS is capable of providing low-resolution tertiary structure information under physiological conditions and with less intensive sample preparation and data analysis requirements than XRC, NMR and cryo-EM. In this article, we describe best practices involved in the process of RNA and RNA-protein sample preparation, SAXS data collection, data analysis, and structural model building. PMID:27777026

  14. MD Simulations of tRNA and Aminoacyl-tRNA Synthetases: Dynamics, Folding, Binding, and Allostery

    PubMed Central

    Li, Rongzhong; Macnamara, Lindsay M.; Leuchter, Jessica D.; Alexander, Rebecca W.; Cho, Samuel S.

    2015-01-01

    While tRNA and aminoacyl-tRNA synthetases are classes of biomolecules that have been extensively studied for decades, the finer details of how they carry out their fundamental biological functions in protein synthesis remain a challenge. Recent molecular dynamics (MD) simulations are verifying experimental observations and providing new insight that cannot be addressed from experiments alone. Throughout the review, we briefly discuss important historical events to provide a context for how far the field has progressed over the past few decades. We then review the background of tRNA molecules, aminoacyl-tRNA synthetases, and current state of the art MD simulation techniques for those who may be unfamiliar with any of those fields. Recent MD simulations of tRNA dynamics and folding and of aminoacyl-tRNA synthetase dynamics and mechanistic characterizations are discussed. We highlight the recent successes and discuss how important questions can be addressed using current MD simulations techniques. We also outline several natural next steps for computational studies of AARS:tRNA complexes. PMID:26184179

  15. ISAP: ISO Spectral Analysis Package

    NASA Astrophysics Data System (ADS)

    Ali, Babar; Bauer, Otto; Brauher, Jim; Buckley, Mark; Harwood, Andrew; Hur, Min; Khan, Iffat; Li, Jing; Lord, Steve; Lutz, Dieter; Mazzarella, Joe; Molinari, Sergio; Morris, Pat; Narron, Bob; Seidenschwang, Karla; Sidher, Sunil; Sturm, Eckhard; Swinyard, Bruce; Unger, Sarah; Verstraete, Laurent; Vivares, Florence; Wieprecht, Ecki

    2014-03-01

    ISAP, written in IDL, simplifies the process of visualizing, subsetting, shifting, rebinning, masking, combining scans with weighted means or medians, filtering, and smoothing Auto Analysis Results (AARs) from post-pipeline processing of the Infrared Space Observatory's (ISO) Short Wavelength Spectrometer (SWS) and Long Wavelength Spectrometer (LWS) data. It can also be applied to PHOT-S and CAM-CVF data, and data from practically any spectrometer. The result of a typical ISAP session is expected to be a "simple spectrum" (single-valued spectrum which may be resampled to a uniform wavelength separation if desired) that can be further analyzed and measured either with other ISAP functions, native IDL functions, or exported to other analysis package (e.g., IRAF, MIDAS) if desired. ISAP provides many tools for further analysis, line-fitting, and continuum measurements, such as routines for unit conversions, conversions from wavelength space to frequency space, line and continuum fitting, flux measurement, synthetic photometry and models such as a zodiacal light model to predict and subtract the dominant foreground at some wavelengths.

  16. Structure of human cytosolic phenylalanyl-tRNA synthetase: evidence for kingdom-specific design of the active sites and tRNA binding patterns.

    PubMed

    Finarov, Igal; Moor, Nina; Kessler, Naama; Klipcan, Liron; Safro, Mark G

    2010-03-10

    The existence of three types of phenylalanyl-tRNA synthetase (PheRS), bacterial (alphabeta)(2), eukaryotic/archaeal cytosolic (alphabeta)(2), and mitochondrial alpha, is a prominent example of structural diversity within the aaRS family. PheRSs have considerably diverged in primary sequences, domain compositions, and subunit organizations. Loss of the anticodon-binding domain B8 in human cytosolic PheRS (hcPheRS) is indicative of variations in the tRNA(Phe) binding and recognition as compared to bacterial PheRSs. We report herein the crystal structure of hcPheRS in complex with phenylalanine at 3.3 A resolution. A novel structural module has been revealed at the N terminus of the alpha subunit. It stretches out into the solvent of approximately 80 A and is made up of three structural domains (DBDs) possessing DNA-binding fold. The dramatic reduction of aminoacylation activity for truncated N terminus variants coupled with structural data and tRNA-docking model testify that DBDs play crucial role in hcPheRS activity.

  17. XCALIBUR: a Vertical Takeoff TSTO RLV Concept with a HEDM Upperstage and a Scram-Rocket Booster

    NASA Astrophysics Data System (ADS)

    Bradford, J.

    2002-01-01

    A new 3rd generation, two-stage-to-orbit (TSTO) reusable launch vehicle (RLV) has been designed. The Xcalibur concept represents a novel approach due to its integration method for the upperstage element of the system. The vertical-takeoff booster, which is powered by rocket-based combined-cycle (RBCC) engines, carries the upperstage internally in the aft section of the airframe to a Mach 15 staging condition. The upperstage is released from the booster and carries the 6,820 kg of payload to low earth orbit (LEO) using its high energy density matter (HEDM) propulsion system. The booster element is capable of returning to the original launch site in a ramjet-cruise propulsion mode. Both the booster and the upperstage utilize advanced technologies including: graphite-epoxy tanks, metal-matrix composites, UHTC TPS materials, electro- mechanical actuators (EMAs), and lightweight subsystems (avionics, power distribution, etc.). The booster system is enabled main propulsion system which utilizes four RBCC engines. These engines operate in four distinct modes: air- augmented rocket (AAR), ramjet, scram-rocket, and all-rocket. The booster operates in AAR mode from takeoff to Mach 3, with ramjet mode operation from Mach 3 to Mach 6. The rocket re-ignition for scram-rocket mode occurs at Mach 6, with all-rocket mode from Mach 14 to the staging condition. The extended utilization of the scram-rocket mode greatly improves vehicle performance by providing superior vehicle acceleration when compared to the scramjet mode performance over the same flight region. Results indicate that the specific impulse penalty due to the scram-rocket mode operation is outweighed by the reduced flight time, smaller vehicle size due to increased mixture ratio, and lower allowable maximum dynamic pressure. A complete vehicle system life-cycle analysis was performed in an automated, multi-disciplinary design environment. Automated disciplinary performance analysis tools include: trajectory (POST

  18. Annual and seasonal mass balances of Chhota Shigri Glacier (benchmark glacier, Western Himalaya), India

    NASA Astrophysics Data System (ADS)

    Mandal, Arindan; Ramanathan, Alagappan; Farooq Azam, Mohd; Wagnon, Patrick; Vincent, Christian; Linda, Anurag; Sharma, Parmanand; Angchuk, Thupstan; Bahadur Singh, Virendra; Pottakkal, Jose George; Kumar, Naveen; Soheb, Mohd

    2015-04-01

    Several studies on Himalayan glaciers have been recently initiated as they are of particular interest in terms of future water supply, regional climate change and sea-level rise. In 2002, a long-term monitoring program was initiated on Chhota Shigri Glacier (15.7 square km, 9 km long, 6263-4050 m a.s.l.) located in Lahaul and Spiti Valley, Himachal Pradesh, India. This glacier lies in the monsoon-arid transition zone (western Himalaya) and is a representative glacier in Lahaul and Spiti Valley. While annual mass balances have been measured continuously since 2002 using the glaciological method, seasonal scale observations began in 2009. The annual and seasonal mass balances were then analyzed along with meteorological conditions in order to understand the role of winter and summer balances on annual glacier-wide mass balance of Chhota Shigri glacier. During the period 2002-2013, the glacier experienced a negative glacier-wide mass balance of -0.59±0.40 m w.e. a-1 with a cumulative glaciological mass balance of -6.45 m w.e. Annual glacier-wide mass balances were negative except for four years (2004/05, 2008/09, 2009/10 and 2010/11) where it was generally close to balanced conditions. Equilibrium line altitude (ELA) for steady state condition is calculated as 4950 m a.s.l. corresponding to an accumulation area ratio (AAR) of 62% using annual glacier-wide mass balance, ELA and AAR data between 2002 and 2013. The winter glacier-wide mass balance between 2009 and 2013 ranges from a maximum value of 1.38 m w.e. in 2009/10 to a minimum value of 0.89 in 2012/13 year whereas the summer glacier-wide mass balance varies from the highest value of -0.95 m w.e. in 2010/11 to the lowest value of -1.72 m w.e. in 2011/12 year. The mean vertical mass balance gradient between 2002 and 2013 was 0.66 m w.e. (100 m)-1 quite similar to Alps, Nepalese Himalayas etc. Over debris covered area, the gradients are highly variable with a negative mean value of -2.15 m w.e. (100 m)-1 over 2002

  19. Fluid regimes during late stages of a continental collision: Physical, chemical, and stable isotope measurements of fluid inclusions in fissure quartz from a geotraverse through the Central Alps, Switzerland

    NASA Astrophysics Data System (ADS)

    Mullis, Josef; Dubessy, Jean; Poty, Bernard; O'Neil, James

    1994-05-01

    Fluid evolution during neo-alpine metamorphism during late stages of the continental collision between Europe and Africa was studied by analyzing fluid inclusions in alpine fissure quartz collected in forty-nine localities along a geotraverse through the Central Alps, Switzerland. The methods employed include microthermometry, micro-Raman spectroscopy, K/Na thermometry, and stable isotope analysis. Early fluid inclusions provide evidence of close to peak metamorphic temperatures of the late Tertiary or neo-alpine metamorphic event. Fluid composition evolved along the geotraverse from north to south as follows: higher hydrocarbons were dominant in the low- and medium-grade diagenetic zones, methane was the main volatile in the high-grade diagenetic and low-grade anchizone, water dominated in the highgrade anchizone and low-grade epizone, with CO2 > 10 mol% in the high-grade epizone and in the mesozone. Higher hydrocarbons and CH 4 were the products of kerogen maturation and cracking of preexisting petroleum. Large water supplies originated from the dehydration of cooler metasedimentary rocks that were overthrust by crystalline basements of the Lepontines, Aar, and Gotthard massifs. Carbon isotope analyses suggest that the CO 2 component was derived from oxidation of graphitic matter, especially in the vicinity of sulfate-bearing metasediments and from decarbonation reactions. In the Aar and Gotthard massifs as well as in the Helvetic Axen nappe and its underlying North Helvetic flysch, high fluid pressures prevailed and favored nappe transport. By contrast, in the southern Lepontine area, very low early fluid pressures were probably related to dry rocks and scarce metasediments, and to high geothermal gradients that resulted from intense uplift and erosion between 26 and 18 Ma. Retrograde fluid evolution was recorded by a succession of fluid inclusion populations in each alpine fissure. It was controlled by uplift and cooling and characterized by decreasing contents

  20. [Effect of parecoxib on hippocampal inflammation and memory function in aged rats after splenectomy].

    PubMed

    Li, Peng; Yang, Mengchang; Yang, Xue; Liu, Ziling

    2016-06-28

    To explore the effect of parecoxib on hippocampal inflammation and short-term memory function after splenectomy in aged rats.
 A total of 90 aged male SD rats were randomly divided into 9 groups (all n=10): a control group (Group C), an anesthesia day 1 group (A1 group), an operation day 1 group (O1 group), a saline day 1 group (S1 group), a parecoxib day 1 group (P1 group), an anesthesia day 3 group (A3 group), an operation day 3 group (O3 group), a saline day 3 group (S3 group), and a parecoxib day 3 group (P3 group). In the A1 group and A3 group, rats were anesthetized by intraperitoneal injection of pentobarbital sodium. Under anesthesia condition, rats in the O1 group and O3 group underwent splenectomy. One hour before splenectomy, rats in the P1 group and P3 group received parecoxib injection of 10 mg/kg via tail vein. In the S1 group and S3 group, rats received the same dose of saline. The rats were trained for 5 days in shuttle box before anesthesia, surgery and drug treatment. After shuttle box test, the rats were killed at postoperative 1 and 3 d. The hippocampus was isolated to measure the CD11b expression by immunofluorescent staining, and TNF-α, IL-1 and COX-2 mRNA expression by RT-PCR.
 Compared with the Group C, the electric shock time was increased in the O1 and O3 groups, but the active escape time was shortened and the active avoidance reaction (AAR) was decreased (all P<0.01). Compared with the O1 or O3 group, the electric shock time was shortened, the active escape time and AAR was increased in the P1 or P3 group (all P<0.05). There were more CD11b positive cells and TNF-α, IL-1β, COX-2 mRNA expression in hippocampus in the O1, O3, S1 or S3 group compared with the Group C (all P<0.01). Both CD11b positive cells and TNF-α, IL-1β, COX-2 mRNA expression were decreased in the P1 or P3 group compared with that in the O1 or O3 group (all P<0.01). 
 The parecoxib could reduce hippocampal inflammation and improve short-term memory function

  1. The MIS 5 palaeoenvironmental record in the SE Mediterranean coast of the Iberian Peninsula (Río Antas, Almería, Spain)

    NASA Astrophysics Data System (ADS)

    Torres, T.; Ortiz, J. E.; Blázquez, A. M.; Ruiz Zapata, B.; Gil, M. J.; Martín, T.; Sánchez-Palencia, Y.

    2015-08-01

    Landwards of a MIS5 bar, a borehole core (SRA) was analyzed to establish the relationship between the lagoonal record and the raised beach deposits in the surroundings of the Antas river mouth and to reconstruct the Pleistocene palaeoenvironmental evolution of the southern Mediterranean coast of the Iberian Peninsula. 63 samples were recovered for amino acid racemization dating, 86 samples for sedimentological and paleontological determination, 37 samples for pollen identification and 54 for biomarker analysis. AAR revealed that the borehole record contains MIS11, MIS6 and MIS5 deposits, the latter extensively represented. During the end of MIS6 and MIS5, a sand barrier developed and created a shallow lagoon with alternating terrestrial inputs this process being common in other Mediterranean realms. Litho- and biofacies allowed the identification of distinct paleoenvironments through time, with the presence of a lagoonal environment alternating with alluvial fan progradation. Biomarkers indicated constant input from terrestrial plants, together with variable development of aquatic macrophytes. The palynological content allowed the reconstruction of the paleoclimatological conditions during MIS6 and 5, with evidence of seven scenarios characterized by alternating arid and relatively humid conditions.

  2. Increased IGFBP-1 phosphorylation in response to leucine deprivation is mediated by CK2 and PKC

    PubMed Central

    Malkani, Niyati; Biggar, Kyle; Shehab, Majida Abu; Li, Shawn; Jansson, Thomas; Gupta, Madhulika B.

    2016-01-01

    Insulin-like growth factor binding protein-1 (IGFBP-1), secreted by fetal liver, is a key regulator of IGF-I bioavailability and fetal growth. IGFBP-1 phosphorylation decreases IGF-I bioavailability and diminishes its growth-promoting effects. Growth-restricted fetuses have decreased levels of circulating essential amino acids. We recently showed that IGFBP-1 hyperphosphorylation (pSer101/119/169) in response to leucine deprivation is regulated via activation of the amino acid response (AAR) in HepG2 cells. Here we investigated nutrient-sensitive protein kinases CK2/PKC/PKA in mediating IGFBP-1 phosphorylation in leucine deprivation. We demonstrated that leucine deprivation stimulated CK2 activity (enzymatic assay) and induced IGFBP-1 phosphorylation (immunoblotting/MRM-MS). Inhibition (pharmacological/siRNA) of CK2/PKC, but not PKA, prevented IGFBP-1 hyperphosphorylation in leucine deprivation. PKC inhibition also prevented leucine deprivation-stimulated CK2 activity. Functionally, leucine deprivation decreased IGF-I-induced-IGF-1R autophosphorylation when CK2/PKC were not inhibited. Our data strongly support that PKC promotes leucine deprivation-induced IGFBP-1 hyperphosphorylation via CK2 activation, mechanistically linking decreased amino acid availability and reduced fetal growth. PMID:26733150

  3. Transcriptome-wide selection of a reliable set of reference genes for gene expression studies in potato cyst nematodes (Globodera spp.).

    PubMed

    Sabeh, Michael; Duceppe, Marc-Olivier; St-Arnaud, Marc; Mimee, Benjamin

    2018-01-01

    Relative gene expression analyses by qRT-PCR (quantitative reverse transcription PCR) require an internal control to normalize the expression data of genes of interest and eliminate the unwanted variation introduced by sample preparation. A perfect reference gene should have a constant expression level under all the experimental conditions. However, the same few housekeeping genes selected from the literature or successfully used in previous unrelated experiments are often routinely used in new conditions without proper validation of their stability across treatments. The advent of RNA-Seq and the availability of public datasets for numerous organisms are opening the way to finding better reference genes for expression studies. Globodera rostochiensis is a plant-parasitic nematode that is particularly yield-limiting for potato. The aim of our study was to identify a reliable set of reference genes to study G. rostochiensis gene expression. Gene expression levels from an RNA-Seq database were used to identify putative reference genes and were validated with qRT-PCR analysis. Three genes, GR, PMP-3, and aaRS, were found to be very stable within the experimental conditions of this study and are proposed as reference genes for future work.

  4. The Role of Adenosine A2A Receptor, CYP450s, and PPARs in the Regulation of Vascular Tone

    PubMed Central

    Khayat, Maan T.

    2017-01-01

    Adenosine is an endogenous mediator involved in a myriad of physiologic functions, including vascular tone regulation. It is also implicated in some pathologic conditions. Four distinct receptor subtypes mediate the effects of adenosine, such as its role in the regulation of the vascular tone. Vascular tone regulation is a complex and continuous process which involves many mechanisms and mediators that are not fully disclosed. The vascular endothelium plays a pivotal role in regulating blood flow to and from all body organs. Also, the vascular endothelium is not merely a physical barrier; it is a complex tissue with numerous functions. Among adenosine receptors, A2A receptor subtype (A2AAR) stands out as the primary receptor responsible for the vasodilatory effects of adenosine. This review focuses on important effectors of the vascular endothelium, including adenosine, adenosine receptors, EETs (epoxyeicosatrienoic acids), HETEs (hydroxyeicosatetraenoic acids), PPARs (peroxisome proliferator-activated receptors), and KATP channels. Given the impact of vascular tone regulation in cardiovascular physiology and pathophysiology, better understanding of the mechanisms affecting it could have a significant potential for developing therapeutic agents for cardiovascular diseases. PMID:28884118

  5. A Multiple Aminoacyl-tRNA Synthetase Complex That Enhances tRNA-Aminoacylation in African Trypanosomes

    PubMed Central

    Cestari, Igor; Kalidas, Savitha; Monnerat, Severine; Anupama, Atashi; Phillips, Margaret A.

    2013-01-01

    The genes for all cytoplasmic and potentially all mitochondrial aminoacyl-tRNA synthetases (aaRSs) were identified, and all those tested by RNA interference were found to be essential for the growth of Trypanosoma brucei. Some of these enzymes were localized to the cytoplasm or mitochondrion, but most were dually localized to both cellular compartments. Cytoplasmic T. brucei aaRSs were organized in a multiprotein complex in both bloodstream and procyclic forms. The multiple aminoacyl-tRNA synthetase (MARS) complex contained at least six aaRS enzymes and three additional non-aaRS proteins. Steady-state kinetic studies showed that association in the MARS complex enhances tRNA-aminoacylation efficiency, which is in part dependent on a MARS complex-associated protein (MCP), named MCP2, that binds tRNAs and increases their aminoacylation by the complex. Conditional repression of MCP2 in T. brucei bloodstream forms resulted in reduced parasite growth and infectivity in mice. Thus, association in a MARS complex enhances tRNA-aminoacylation and contributes to parasite fitness. The MARS complex may be part of a cellular regulatory system and a target for drug development. PMID:24126051

  6. Alkali-silica reactivity of expanded glass granules in structure of lightweight concrete

    NASA Astrophysics Data System (ADS)

    Bumanis, G.; Bajare, D.; Locs, J.; Korjakins, A.

    2013-12-01

    Main component in the lightweight concrete, which provides its properties, is aggregate. A lot of investigations on alkali silica reaction (ASR) between cement and lightweight aggregates have been done with their results published in the academic literature. Whereas expanded glass granules, which is relatively new product in the market of building materials, has not been a frequent research object. Therefore lightweight granules made from waste glass and eight types of cement with different chemical and mineralogical composition were examined in this research. Expanded glass granules used in this research is commercially available material produced by Penostek. Lightweight concrete mixtures were prepared by using commercial chemical additives to improve workability of concrete. The aim of the study is to identify effect of cement composition to the ASR reaction which occurs between expanded glass granules and binder. Expanded glass granules mechanical and physical properties were determined. In addition, properties of fresh and hardened concrete were determined. The ASR test was processed according to RILEM AAR-2 testing recommendation. Tests with scanning electron microscope and microstructural investigations were performed for expanded glass granules and hardened concrete specimens before and after exposing them in alkali solution.

  7. Turbulent transport and production/destruction of ozone in a boundary layer over complex terrain

    NASA Technical Reports Server (NTRS)

    Greenhut, Gary K.; Jochum, Anne M.; Neininger, Bruno

    1994-01-01

    The first Intensive Observation Period (IOP) of the Swiss air pollution experiment POLLUMET took place in 1990 in the Aare River Valley between Bern and Zurich. During the IOP, fast response measurements of meteorological variables and ozone concentration were made within the boundary layer aboard a motorglider. In addition, mean values of meteorological variables and the concentrations of ozone and other trace species were measured using other aircraft, pilot balloons, tethersondes, and ground stations. Turbulent flux profiles of latent and sensible heat and ozone are calculated from the fast response data. Terms in the ozone mean concentration budget (time rate of change of mean concentration, horizontal advection, and flux divergence) are calculated for stationary time periods both before and after the passage of a cold front. The source/sink term is calculated as a residual in the budget, and its sign and magnitude are related to the measured concentrations of reactive trace species within the boundary layer. Relationships between concentration ratios of trace species and ozone concentration are determined in order to understand the influence of complex terrain on the processes that produce and destroy ozone.

  8. Plasmodium falciparum mitochondria import tRNAs along with an active phenylalanyl-tRNA synthetase.

    PubMed

    Sharma, Arvind; Sharma, Amit

    2015-02-01

    The Plasmodium falciparum protein translation enzymes aminoacyl-tRNA synthetases (aaRSs) are an emergent family of drug targets. The aaRS ensemble catalyses transfer of amino acids to cognate tRNAs, thus providing charged tRNAs for ribosomal consumption. P. falciparum proteome expression relies on a total of 36 aaRSs for the three translationally independent compartments of cytoplasm, apicoplast and mitochondria. In the present study, we show that, of this set of 36, a single genomic copy of mitochondrial phenylalanyl-tRNA synthetase (mFRS) is targeted to the parasite mitochondria, and that the mFRS gene is exclusive to malaria parasites within the apicomplexan phyla. Our protein cellular localization studies based on immunofluorescence data show that, along with mFRS, P. falciparum harbours two more phenylalanyl-tRNA synthetase (FRS) assemblies that are localized to its apicoplast and cytoplasm. The 'extra' mFRS is found in mitochondria of all asexual blood stage parasites and is competent in aminoacylation. We show further that the parasite mitochondria import tRNAs from the cytoplasmic tRNA pool. Hence drug targeting of FRSs presents a unique opportunity to potentially stall protein production in all three parasite translational compartments.

  9. Cloning and expression of a small heat and salt tolerant protein (Hsp22) from Chaetomium globosum.

    PubMed

    Aggarwal, Rashmi; Gupta, Sangeeta; Sharma, Sapna; Banerjee, Sagar; Singh, Priyanka

    2012-11-01

    The present study reports molecular characterization of small heat shock protein gene in Indian isolates of Chaetomium globosum, C. perlucidum, C. reflexum, C. cochlioides and C. cupreum. Six isolates of C. globosum and other species showed a band of 630bp using specific primers. Amplified cDNA product of C. globosum (Cg 1) cloned and sequenced showed 603bp open reading frame encoding 200 amino-acids. The protein sequence had a molecular mass of 22 kDa and was therefore, named Hsp22. BlastX analysis revealed that the gene codes for a protein homologous to previously characterized Hsp22.4 gene from C. globosum (AAR36902.1, XP 001229241.1) and shared 95% identity in amino acid sequence. It also showed varying degree of similarities with small Hsp protein from Neurospora spp. (60%), Myceliophthora sp. (59%), Glomerella sp. (50%), Hypocrea sp. (52%), and Fusarium spp. (51%). This gene was further cloned into pET28a (+) and transformed E. coli BL21 cells were induced by IPTG, and the expressed protein of 30 kDa was analyzed by SDS-PAGE. The IPTG induced transformants displayed significantly greater resistance to NaCl and Na2CO3 stresses.

  10. AarF Domain Containing Kinase 3 (ADCK3) Mutant Cells Display Signs of Oxidative Stress, Defects in Mitochondrial Homeostasis and Lysosomal Accumulation

    PubMed Central

    Cullen, Jason K.; Abdul Murad, Norazian; Yeo, Abrey; McKenzie, Matthew; Ward, Micheal; Chong, Kok Leong; Schieber, Nicole L.; Parton, Robert G.; Lim, Yi Chieh; Wolvetang, Ernst; Maghzal, Ghassan J.; Stocker, Roland; Lavin, Martin F.

    2016-01-01

    Autosomal recessive ataxias are a clinically diverse group of syndromes that in some cases are caused by mutations in genes with roles in the DNA damage response, transcriptional regulation or mitochondrial function. One of these ataxias, known as Autosomal Recessive Cerebellar Ataxia Type-2 (ARCA-2, also known as SCAR9/COQ10D4; OMIM: #612016), arises due to mutations in the ADCK3 gene. The product of this gene (ADCK3) is an atypical kinase that is thought to play a regulatory role in coenzyme Q10 (CoQ10) biosynthesis. Although much work has been performed on the S. cerevisiae orthologue of ADCK3, the cellular and biochemical role of its mammalian counterpart, and why mutations in this gene lead to human disease is poorly understood. Here, we demonstrate that ADCK3 localises to mitochondrial cristae and is targeted to this organelle via the presence of an N-terminal localisation signal. Consistent with a role in CoQ10 biosynthesis, ADCK3 deficiency decreased cellular CoQ10 content. In addition, endogenous ADCK3 was found to associate in vitro with recombinant Coq3, Coq5, Coq7 and Coq9, components of the CoQ10 biosynthetic machinery. Furthermore, cell lines derived from ARCA-2 patients display signs of oxidative stress, defects in mitochondrial homeostasis and increases in lysosomal content. Together, these data shed light on the possible molecular role of ADCK3 and provide insight into the cellular pathways affected in ARCA-2 patients. PMID:26866375

  11. Transfusion of Plasma Collected at Late Phase after Preconditioning Reduces Myocardial Infarct Size Induced by Ischemia-reperfusion in Rats In vivo.

    PubMed

    Zhao, Yang; Zheng, Zhi-Nan; Cheung, Chi-Wai; Zuo, Zhi-Yi; Jin, San-Qing

    2017-02-05

    Plasma transfusion is a common clinical practice. Remote ischemic preconditioning (RIPC) protects organs against ischemia-reperfusion (IR) injury. Whether preconditioned plasma (PP), collected at late phase after RIPC, could protect organs against IR injury in vivo is unknown. This study explored whether transfusion of PP could reduce myocardial infarct size (IS) after IR in rat in vivo. Eighty Lewis rats were randomized to eight groups (n = 10 for each group). Two groups of plasma donor rats donated plasma at 48 h after transient limb ischemia (PP) or control protocol (nonpreconditioned plasma [NPP]). Six groups of recipient rats received normal saline (NS; NS-IR 1, and NS-IR 24 groups), NPP (NPP-IR 1 and NPP-IR 24 groups), or PP (PP-IR 1 and PP-IR 24 groups) at one or 24 h before myocardial IR. Myocardial IR consisted of 30-min left anterior descending (LAD) coronary artery occlusion and 180-min reperfusion. The area at risk (AAR) and infarct area were determined by double-staining with Evans blue and triphenyltetrazolium chloride. IS was calculated by infarct area divided by AAR. This was a 3 × 2 factorial design study, and factorial analysis was used to evaluate the data. If an interaction between the fluid and transfusion time existed, one-way analysis of variance with Bonferroni correction for multiple comparisons was used to analyze the single effects of fluid type when the transfusion time was fixed. IS in the NPP-IR 1 and PP-IR 1 groups was smaller than in the NS-IR 1 group (F = 6.838, P = 0.005; NPP-IR 1: 57 ± 8% vs. NS-IR1: 68 ± 6%, t = 2.843, P = 0.020; PP-IR 1: 56 ± 8% vs. NS-IR 1: 68 ± 6%, t = 3.102, P = 0.009), but no significant difference was detected between the NPP-IR 1 and PP-IR 1 groups (57 ± 8% vs. 56 ± 8%, t = 0.069, P = 1.000). IS in the NPP-IR 24 and PP-IR 24 groups was smaller than in the NS-IR 24 group (F = 24.796, P< 0.001; NPP-IR 24: 56% ± 7% vs. NS-IR 24: 68 ± 7%, t = 3.102, P = 0.026; PP-IR 24: 40 ± 9% vs. NS-IR 24: 68 ± 7

  12. Comparison of serological assessments in the diagnosis of liver fibrosis in bile duct ligation mice.

    PubMed

    Xie, Chengxia; Ma, Bo; Wang, Ning; Wan, Lin

    2017-08-01

    Liver fibrosis assessment is essential to make a prognosis and to determine the appropriate anti-fibrosis treatment. Non-invasive serum markers are widely studied in patients to assess liver fibrosis due to the limitations of liver biopsy. When using animal models to study the mechanism and intervention of hepatic fibrosis, serum markers might be useful for the continuous assessment of liver fibrosis in individual animals, which could avoid the influence of biological differences between individuals. However, it is unclear whether serum markers can assess hepatic fibrosis in the animal model. In the present study, we evaluated and compared the ability of four serum markers to assess liver fibrosis in bile duct ligation mice. According to the stages of liver fibrosis assessed by pathological changes, mice in this study were divided into five groups (F0, F1, F2, F3, and F4). Subsequently, four serum markers, aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4), and Forns Index, were calculated for each group. Furthermore, the correlations between serum markers and pathological stages and the ability of serological markers to evaluate liver fibrosis were analyzed. AAR, APRI, FIB-4, and Forns Index could significantly distinguish F0-2 from F3-4 mice. APRI, FIB-4, and Forns Index could detect F0-3 from F4 mice. Among these four markers, FIB-4 was the best able to distinguish ≥F2 and ≥F3, with area under the curve values of 0.882 and 0.92, respectively. Forns Index was best for diagnosing F4 with area under the curve value of 0.879. These results demonstrated that serum markers could be used for assessing liver fibrosis in bile duct ligation mice, and therefore, these markers might lead to more accurate diagnostic and therapeutic studies through continuous monitoring in individual animals. Impact statement The assessment of liver fibrosis is

  13. Evolution of aminoacyl-tRNA synthetases--analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events.

    PubMed

    Wolf, Y I; Aravind, L; Grishin, N V; Koonin, E V

    1999-08-01

    Phylogenetic analysis of aminoacyl-tRNA synthetases (aaRSs) of all 20 specificities from completely sequenced bacterial, archaeal, and eukaryotic genomes reveals a complex evolutionary picture. Detailed examination of the domain architecture of aaRSs using sequence profile searches delineated a network of partially conserved domains that is even more elaborate than previously suspected. Several unexpected evolutionary connections were identified, including the apparent origin of the beta-subunit of bacterial GlyRS from the HD superfamily of hydrolases, a domain shared by bacterial AspRS and the B subunit of archaeal glutamyl-tRNA amidotransferases, and another previously undetected domain that is conserved in a subset of ThrRS, guanosine polyphosphate hydrolases and synthetases, and a family of GTPases. Comparison of domain architectures and multiple alignments resulted in the delineation of synapomorphies-shared derived characters, such as extra domains or inserts-for most of the aaRSs specificities. These synapomorphies partition sets of aaRSs with the same specificity into two or more distinct and apparently monophyletic groups. In conjunction with cluster analysis and a modification of the midpoint-rooting procedure, this partitioning was used to infer the likely root position in phylogenetic trees. The topologies of the resulting rooted trees for most of the aaRSs specificities are compatible with the evolutionary "standard model" whereby the earliest radiation event separated bacteria from the common ancestor of archaea and eukaryotes as opposed to the two other possible evolutionary scenarios for the three major divisions of life. For almost all aaRSs specificities, however, this simple scheme is confounded by displacement of some of the bacterial aaRSs by their eukaryotic or, less frequently, archaeal counterparts. Displacement of ancestral eukaryotic aaRS genes by bacterial ones, presumably of mitochondrial origin, was observed for three aaRSs. In contrast

  14. Flow Behavior and Constitutive Equation of Ti-6.5Al-2Sn-4Zr-4Mo-1W-0.2Si Titanium Alloy

    NASA Astrophysics Data System (ADS)

    Yang, Xuemei; Guo, Hongzhen; Liang, Houquan; Yao, Zekun; Yuan, Shichong

    2016-04-01

    In order to get a reliable constitutive equation for the finite element simulation, flow behavior of Ti-6.5Al-2Sn-4Zr-4Mo-1W-0.2Si alloy under high temperature was investigated by carrying a series of isothermal compression tests at temperatures of 1153-1293 K and strain rates of 0.01-10.0 s-1 on the Gleeble-1500 simulator. Results showed that the true stress-strain curves exhibited peaks at small strains, after which the flow stress decreased monotonically. Ultimately, the flow curves reached steady state at the strain of 0.6, showing a dynamic flow softening phenomenon. The effects of strain rate, temperature, and strain on the flow behavior were researched by establishing a constitutive equation. The relations among stress exponent, deformation activation energy, and strain were preliminarily discussed by using strain rate sensitivity exponent and dynamic recrystallization kinetics curve. Stress values predicted by the modified constitutive equation showed a good agreement with the experimental ones. The correlation coefficient ( R) and average absolute relative error (AARE) were 98.2% and 4.88%, respectively, which confirmed that the modified constitutive equation could give an accurate estimation of the flow stress for BT25y titanium alloy.

  15. Coupling suitable prey field to in situ fish larval condition and abundance in a subtropical estuary

    NASA Astrophysics Data System (ADS)

    Machado, Irene; Calliari, Danilo; Denicola, Ana; Rodríguez-Graña, Laura

    2017-03-01

    Survival of fish larvae is influenced by the suitability of the prey field and its variability in time and space. Relationships among food quality, quantity and recruitment have been explored in temperate ecosystems where spawning and secondary production are strongly seasonal, but for subtropical estuaries the mechanisms responsible for larval survival remain poorly identified. This study evaluated the nutritional condition (feeding incidence and AARS activity) and abundance of a multi-specific assemblage of fish larvae from a subtropical estuary in South America (Solís Grande, Uruguay) during the fish reproductive season; and related both variables to prey abundance, composition, size and fatty acids content. The larval assemblage was composed of 13 species belonging to different functional groups and composition varied seasonally. Contrary to expectations larval condition did not match an increase in prey quality. Food availability was high throughout the study period, although significant changes existed in the size and taxonomic structure of the prey assemblage. The temporal succession of complementary factors - temperature, prey composition, abundance and quality - promoted a wide window of opportunity for larvae, where quality seemed to have compensated quantity. Such combination of factors could allow an extended larval survival along the spawning season. These findings underline the importance of a better understanding of subtropical estuaries as nursery areas.

  16. Definition and automatic anatomy recognition of lymph node zones in the pelvis on CT images

    NASA Astrophysics Data System (ADS)

    Liu, Yu; Udupa, Jayaram K.; Odhner, Dewey; Tong, Yubing; Guo, Shuxu; Attor, Rosemary; Reinicke, Danica; Torigian, Drew A.

    2016-03-01

    Currently, unlike IALSC-defined thoracic lymph node zones, no explicitly provided definitions for lymph nodes in other body regions are available. Yet, definitions are critical for standardizing the recognition, delineation, quantification, and reporting of lymphadenopathy in other body regions. Continuing from our previous work in the thorax, this paper proposes a standardized definition of the grouping of pelvic lymph nodes into 10 zones. We subsequently employ our earlier Automatic Anatomy Recognition (AAR) framework designed for body-wide organ modeling, recognition, and delineation to actually implement these zonal definitions where the zones are treated as anatomic objects. First, all 10 zones and key anatomic organs used as anchors are manually delineated under expert supervision for constructing fuzzy anatomy models of the assembly of organs together with the zones. Then, optimal hierarchical arrangement of these objects is constructed for the purpose of achieving the best zonal recognition. For actual localization of the objects, two strategies are used -- optimal thresholded search for organs and one-shot method for the zones where the known relationship of the zones to key organs is exploited. Based on 50 computed tomography (CT) image data sets for the pelvic body region and an equal division into training and test subsets, automatic zonal localization within 1-3 voxels is achieved.

  17. Allosteric regulation of rhomboid intramembrane proteolysis.

    PubMed

    Arutyunova, Elena; Panwar, Pankaj; Skiba, Pauline M; Gale, Nicola; Mak, Michelle W; Lemieux, M Joanne

    2014-09-01

    Proteolysis within the lipid bilayer is poorly understood, in particular the regulation of substrate cleavage. Rhomboids are a family of ubiquitous intramembrane serine proteases that harbour a buried active site and are known to cleave transmembrane substrates with broad specificity. In vitro gel and Förster resonance energy transfer (FRET)-based kinetic assays were developed to analyse cleavage of the transmembrane substrate psTatA (TatA from Providencia stuartii). We demonstrate significant differences in catalytic efficiency (kcat/K0.5) values for transmembrane substrate psTatA (TatA from Providencia stuartii) cleavage for three rhomboids: AarA from P. stuartii, ecGlpG from Escherichia coli and hiGlpG from Haemophilus influenzae demonstrating that rhomboids specifically recognize this substrate. Furthermore, binding of psTatA occurs with positive cooperativity. Competitive binding studies reveal an exosite-mediated mode of substrate binding, indicating allostery plays a role in substrate catalysis. We reveal that exosite formation is dependent on the oligomeric state of rhomboids, and when dimers are dissociated, allosteric substrate activation is not observed. We present a novel mechanism for specific substrate cleavage involving several dynamic processes including positive cooperativity and homotropic allostery for this interesting class of intramembrane proteases. © 2014 The Authors.

  18. Allosteric regulation of rhomboid intramembrane proteolysis

    PubMed Central

    Arutyunova, Elena; Panwar, Pankaj; Skiba, Pauline M; Gale, Nicola; Mak, Michelle W; Lemieux, M Joanne

    2014-01-01

    Proteolysis within the lipid bilayer is poorly understood, in particular the regulation of substrate cleavage. Rhomboids are a family of ubiquitous intramembrane serine proteases that harbour a buried active site and are known to cleave transmembrane substrates with broad specificity. In vitro gel and Förster resonance energy transfer (FRET)-based kinetic assays were developed to analyse cleavage of the transmembrane substrate psTatA (TatA from Providencia stuartii). We demonstrate significant differences in catalytic efficiency (kcat/K0.5) values for transmembrane substrate psTatA (TatA from Providencia stuartii) cleavage for three rhomboids: AarA from P. stuartii, ecGlpG from Escherichia coli and hiGlpG from Haemophilus influenzae demonstrating that rhomboids specifically recognize this substrate. Furthermore, binding of psTatA occurs with positive cooperativity. Competitive binding studies reveal an exosite-mediated mode of substrate binding, indicating allostery plays a role in substrate catalysis. We reveal that exosite formation is dependent on the oligomeric state of rhomboids, and when dimers are dissociated, allosteric substrate activation is not observed. We present a novel mechanism for specific substrate cleavage involving several dynamic processes including positive cooperativity and homotropic allostery for this interesting class of intramembrane proteases. PMID:25009246

  19. Rapid prototyping of an EEG-based brain-computer interface (BCI).

    PubMed

    Guger, C; Schlögl, A; Neuper, C; Walterspacher, D; Strein, T; Pfurtscheller, G

    2001-03-01

    The electroencephalogram (EEG) is modified by motor imagery and can be used by patients with severe motor impairments (e.g., late stage of amyotrophic lateral sclerosis) to communicate with their environment. Such a direct connection between the brain and the computer is known as an EEG-based brain-computer interface (BCI). This paper describes a new type of BCI system that uses rapid prototyping to enable a fast transition of various types of parameter estimation and classification algorithms to real-time implementation and testing. Rapid prototyping is possible by using Matlab, Simulink, and the Real-Time Workshop. It is shown how to automate real-time experiments and perform the interplay between on-line experiments and offline analysis. The system is able to process multiple EEG channels on-line and operates under Windows 95 in real-time on a standard PC without an additional digital signal processor (DSP) board. The BCI can be controlled over the Internet, LAN or modem. This BCI was tested on 3 subjects whose task it was to imagine either left or right hand movement. A classification accuracy between 70% and 95% could be achieved with two EEG channels after some sessions with feedback using an adaptive autoregressive (AAR) model and linear discriminant analysis (LDA).

  20. Ocular Purine Receptors as Drug Targets in the Eye

    PubMed Central

    Civan, Mortimer M.

    2016-01-01

    Abstract Agonists and antagonists of various subtypes of G protein coupled adenosine receptors (ARs), P2Y receptors (P2YRs), and ATP-gated P2X receptor ion channels (P2XRs) are under consideration as agents for the treatment of ocular diseases, including glaucoma and dry eye. Numerous nucleoside and nonnucleoside modulators of the receptors are available as research tools and potential therapeutic molecules. Three of the 4 subtypes of ARs have been exploited with clinical candidate molecules for treatment of the eye: A1, A2A, and A3. An A1AR agonist is in clinical trials for glaucoma, A2AAR reduces neuroinflammation, A3AR protects retinal ganglion cells from apoptosis, and both A3AR agonists and antagonists had been reported to lower intraocular pressure (IOP). Extracellular concentrations of endogenous nucleotides, including dinucleoside polyphosphates, are increased in pathological states, activating P2Y and P2XRs throughout the eye. P2YR agonists, including P2Y2 and P2Y6, lower IOP. Antagonists of the P2X7R prevent the ATP-induced neuronal apoptosis in the retina. Thus, modulators of the purinome in the eye might be a source of new therapies for ocular diseases. PMID:27574786

  1. Comparative Study on the Cellular and Systemic Nutrient Sensing and Intermediary Metabolism after Partial Replacement of Fishmeal by Meat and Bone Meal in the Diet of Turbot (Scophthalmus maximus L.)

    PubMed Central

    Mai, Kangsen; Zhou, Huihui; Xu, Wei; He, Gen

    2016-01-01

    This study was designed to examine the cellular and systemic nutrient sensing mechanisms as well as the intermediary metabolism responses in turbot (Scophthalmus maximus L.) fed with fishmeal diet (FM diet), 45% of FM replaced by meat and bone meal diet (MBM diet) or MBM diet supplemented with essential amino acids to match the amino acid profile of FM diet (MBM+AA diet). During the one month feeding trial, feed intake was not affected by the different diets. However, MBM diet caused significant reduction of specific growth rate and nutrient retentions. Compared with the FM diet, MBM diet down-regulated target of rapamycin (TOR) and insulin-like growth factor (IGFs) signaling pathways, whereas up-regulated the amino acid response (AAR) signaling pathway. Moreover, MBM diet significantly decreased glucose and lipid anabolism, while increased muscle protein degradation and lipid catabolism in liver. MBM+AA diet had no effects on improvement of MBM diet deficiencies. Compared with fasted, re-feeding markedly activated the TOR signaling pathway, IGF signaling pathway and glucose, lipid metabolism, while significantly depressed the protein degradation signaling pathway. These results thus provided a comprehensive display of molecular responses and a better explanation of deficiencies generated after fishmeal replacement by other protein sources. PMID:27802317

  2. Phylogenetic analysis of highly pathogenic avian influenza A(H5N8) virus outbreak strains provides evidence for four separate introductions and one between-poultry farm transmission in the Netherlands, November 2014.

    PubMed

    Bouwstra, R J; Koch, G; Heutink, R; Harders, F; van der Spek, A; Elbers, A R; Bossers, A

    2015-07-02

    Phylogenetic analysis of highly pathogenic avian influenza A(H5N8) virus strains causing outbreaks in Dutch poultry farms in 2014 provides evidence for separate introduction of the virus in four outbreaks in farms located 16-112 km from each other and for between-farm transmission between the third and fourth outbreak in farms located 550 m from each other. In addition, the analysis showed that all European and two Japanese H5N8 virus strains are very closely related and seem to originate from a calculated common ancestor, which arose between July and September 2014. Our findings suggest that the Dutch outbreak virus strain 'Ter Aar' and the first German outbreak strain from 2014 shared a common ancestor. In addition, the data indicate that the Dutch outbreak viruses descended from an H5N8 virus that circulated around 2009 in Asia, possibly China, and subsequently spread to South Korea and Japan and finally also to Europe. Evolution of the virus seemed to follow a parallel track in Japan and Europe, which supports the hypothesis that H5N8 virus was exchanged between migratory wild waterfowl at their breeding grounds in Siberia and from there was carried by migrating waterfowl to Europe.

  3. A Comparative Study on Johnson Cook, Modified Zerilli-Armstrong and Arrhenius-Type Constitutive Models to Predict High-Temperature Flow Behavior of Ti-6Al-4V Alloy in α + β Phase

    NASA Astrophysics Data System (ADS)

    Cai, Jun; Wang, Kuaishe; Han, Yingying

    2016-03-01

    True stress and true strain values obtained from isothermal compression tests over a wide temperature range from 1,073 to 1,323 K and a strain rate range from 0.001 to 1 s-1 were employed to establish the constitutive equations based on Johnson Cook, modified Zerilli-Armstrong (ZA) and strain-compensated Arrhenius-type models, respectively, to predict the high-temperature flow behavior of Ti-6Al-4V alloy in α + β phase. Furthermore, a comparative study has been made on the capability of the three models to represent the elevated temperature flow behavior of Ti-6Al-4V alloy. Suitability of the three models was evaluated by comparing both the correlation coefficient R and the average absolute relative error (AARE). The results showed that the Johnson Cook model is inadequate to provide good description of flow behavior of Ti-6Al-4V alloy in α + β phase domain, while the predicted values of modified ZA model and the strain-compensated Arrhenius-type model could agree well with the experimental values except under some deformation conditions. Meanwhile, the modified ZA model could track the deformation behavior more accurately than other model throughout the entire temperature and strain rate range.

  4. Aminoacyl-tRNA synthetase deficiencies in search of common themes.

    PubMed

    Fuchs, Sabine A; Schene, Imre F; Kok, Gautam; Jansen, Jurriaan M; Nikkels, Peter G J; van Gassen, Koen L I; Terheggen-Lagro, Suzanne W J; van der Crabben, Saskia N; Hoeks, Sanne E; Niers, Laetitia E M; Wolf, Nicole I; de Vries, Maaike C; Koolen, David A; Houwen, Roderick H J; Mulder, Margot F; van Hasselt, Peter M

    2018-06-06

    Pathogenic variations in genes encoding aminoacyl-tRNA synthetases (ARSs) are increasingly associated with human disease. Clinical features of autosomal recessive ARS deficiencies appear very diverse and without apparent logic. We searched for common clinical patterns to improve disease recognition, insight into pathophysiology, and clinical care. Symptoms were analyzed in all patients with recessive ARS deficiencies reported in literature, supplemented with unreported patients evaluated in our hospital. In literature, we identified 107 patients with AARS, DARS, GARS, HARS, IARS, KARS, LARS, MARS, RARS, SARS, VARS, YARS, and QARS deficiencies. Common symptoms (defined as present in ≥4/13 ARS deficiencies) included abnormalities of the central nervous system and/or senses (13/13), failure to thrive, gastrointestinal symptoms, dysmaturity, liver disease, and facial dysmorphisms. Deep phenotyping of 5 additional patients with unreported compound heterozygous pathogenic variations in IARS, LARS, KARS, and QARS extended the common phenotype with lung disease, hypoalbuminemia, anemia, and renal tubulopathy. We propose a common clinical phenotype for recessive ARS deficiencies, resulting from insufficient aminoacylation activity to meet translational demand in specific organs or periods of life. Assuming residual ARS activity, adequate protein/amino acid supply seems essential instead of the traditional replacement of protein by glucose in patients with metabolic diseases.

  5. Autonomous Aerial Refueling Ground Test Demonstration—A Sensor-in-the-Loop, Non-Tracking Method

    PubMed Central

    Chen, Chao-I; Koseluk, Robert; Buchanan, Chase; Duerner, Andrew; Jeppesen, Brian; Laux, Hunter

    2015-01-01

    An essential capability for an unmanned aerial vehicle (UAV) to extend its airborne duration without increasing the size of the aircraft is called the autonomous aerial refueling (AAR). This paper proposes a sensor-in-the-loop, non-tracking method for probe-and-drogue style autonomous aerial refueling tasks by combining sensitivity adjustments of a 3D Flash LIDAR camera with computer vision based image-processing techniques. The method overcomes the inherit ambiguity issues when reconstructing 3D information from traditional 2D images by taking advantage of ready to use 3D point cloud data from the camera, followed by well-established computer vision techniques. These techniques include curve fitting algorithms and outlier removal with the random sample consensus (RANSAC) algorithm to reliably estimate the drogue center in 3D space, as well as to establish the relative position between the probe and the drogue. To demonstrate the feasibility of the proposed method on a real system, a ground navigation robot was designed and fabricated. Results presented in the paper show that using images acquired from a 3D Flash LIDAR camera as real time visual feedback, the ground robot is able to track a moving simulated drogue and continuously narrow the gap between the robot and the target autonomously. PMID:25970254

  6. Characterization factors for thermal pollution in freshwater aquatic environments.

    PubMed

    Verones, Francesca; Hanafiah, Marlia Mohd; Pfister, Stephan; Huijbregts, Mark A J; Pelletier, Gregory J; Koehler, Annette

    2010-12-15

    To date the impact of thermal emissions has not been addressed in life cycle assessment despite the narrow thermal tolerance of most aquatic species. A method to derive characterization factors for the impact of cooling water discharges on aquatic ecosystems was developed which uses space and time explicit integration of fate and effects of water temperature changes. The fate factor is calculated with a 1-dimensional steady-state model and reflects the residence time of heat emissions in the river. The effect factor specifies the loss of species diversity per unit of temperature increase and is based on a species sensitivity distribution of temperature tolerance intervals for various aquatic species. As an example, time explicit characterization factors were calculated for the cooling water discharge of a nuclear power plant in Switzerland, quantifying the impact on aquatic ecosystems of the rivers Aare and Rhine. The relative importance of the impact of these cooling water discharges was compared with other impacts in life cycle assessment. We found that thermal emissions are relevant for aquatic ecosystems compared to other stressors, such as chemicals and nutrients. For the case of nuclear electricity investigated, thermal emissions contribute between 3% and over 90% to Ecosystem Quality damage.

  7. Nitric oxide for inhalation in ST-elevation myocardial infarction (NOMI): a multicentre, double-blind, randomized controlled trial.

    PubMed

    Janssens, Stefan P; Bogaert, Jan; Zalewski, Jaroslaw; Toth, Attila; Adriaenssens, Tom; Belmans, Ann; Bennett, Johan; Claus, Piet; Desmet, Walter; Dubois, Christophe; Goetschalckx, Kaatje; Sinnaeve, Peter; Vandenberghe, Katleen; Vermeersch, Pieter; Lux, Arpad; Szelid, Zsolt; Durak, Monika; Lech, Piotr; Zmudka, Krzysztof; Pokreisz, Peter; Vranckx, Pascal; Merkely, Bela; Bloch, Kenneth D; Van de Werf, Frans

    2018-05-24

    Inhalation of nitric oxide (iNO) during myocardial ischaemia and after reperfusion confers cardioprotection in preclinical studies via enhanced cyclic guanosine monophosphate (cGMP) signalling. We tested whether iNO reduces reperfusion injury in patients with ST-elevation myocardial infarction (STEMI; NCT01398384). We randomized in a double-blind, placebo-controlled study 250 STEMI patients to inhale oxygen with (iNO) or without (CON) 80 parts-per-million NO for 4 h following percutaneous revascularization. Primary efficacy endpoint was infarct size as a fraction of left ventricular (LV) size (IS/LVmass), assessed by delayed enhancement contrast magnetic resonance imaging (MRI). Pre-specified subgroup analysis included thrombolysis-in-myocardial-infarction flow in the infarct-related artery, troponin T levels on admission, duration of symptoms, location of culprit lesion, and intra-arterial nitroglycerine (NTG) use. Secondary efficacy endpoints included IS relative to risk area (IS/AAR), myocardial salvage index, LV functional recovery, and clinical events at 4 and 12 months. In the overall population, IS/LVmass at 48-72 h was 18.0 ± 13.4% in iNO (n = 109) and 19.4 ± 15.4% in CON [n = 116, effect size -1.524%, 95% confidence interval (95% CI) -5.28, 2.24; P = 0.427]. Subgroup analysis indicated consistency across clinical confounders of IS but significant treatment interaction with NTG (P = 0.0093) resulting in smaller IS/LVmass after iNO in NTG-naïve patients (n = 140, P < 0.05). The secondary endpoint IS/AAR was 53 ± 26% with iNO vs. 60 ± 26% in CON (effect size -6.8%, 95% CI -14.8, 1.3, P = 0.09) corresponding to a myocardial salvage index of 47 ± 26% vs. 40 ± 26%, respectively, P = 0.09. Cine-MRI showed similar LV volumes at 48-72 h, with a tendency towards smaller increases in end-systolic and end-diastolic volumes at 4 months in iNO (P = 0.048 and P = 0.06, respectively, n

  8. Programming Post-Translational Control over the Metabolic Labeling of Cellular Proteins with a Noncanonical Amino Acid.

    PubMed

    Thomas, Emily E; Pandey, Naresh; Knudsen, Sarah; Ball, Zachary T; Silberg, Jonathan J

    2017-08-18

    Transcriptional control can be used to program cells to label proteins with noncanonical amino acids by regulating the expression of orthogonal aminoacyl tRNA synthetases (aaRSs). However, we cannot yet program cells to control labeling in response to aaRS and ligand binding. To identify aaRSs whose activities can be regulated by interactions with ligands, we used a combinatorial approach to discover fragmented variants of Escherichia coli methionyl tRNA synthetase (MetRS) that require fusion to associating proteins for maximal activity. We found that these split proteins could be leveraged to create ligand-dependent MetRS using two approaches. When a pair of MetRS fragments was fused to FKBP12 and the FKBP-rapamycin binding domain (FRB) of mTOR and mutations were introduced that direct substrate specificity toward azidonorleucine (Anl), Anl metabolic labeling was significantly enhanced in growth medium containing rapamycin, which stabilizes the FKBP12-FRB complex. In addition, fusion of MetRS fragments to the termini of the ligand-binding domain of the estrogen receptor yielded proteins whose Anl metabolic labeling was significantly enhanced when 4-hydroxytamoxifen (4-HT) was added to the growth medium. These findings suggest that split MetRS can be fused to a range of ligand-binding proteins to create aaRSs whose metabolic labeling activities depend upon post-translational interactions with ligands.

  9. Oligocene-Miocene magnetic stratigraphy carried by biogenic magnetite at sites U1334 and U1335 (equatorial Pacific Ocean)

    NASA Astrophysics Data System (ADS)

    Channell, J. E. T.; Ohneiser, C.; Yamamoto, Y.; Kesler, M. S.

    2013-02-01

    AbstractSediments from the equatorial Pacific Ocean, at the Integrated Ocean Drilling Program sites U1334 and U1335, record reliable magnetic polarity stratigraphies back to ~26.5 Ma (late Oligocene) at sedimentation rates usually in the 5-20 m/Myr range. Putative polarity subchrons that do not appear in current polarity timescales occur within Chrons C5ACr, C5ADn, and C5Bn.1r at Site U1335; and within Chrons C6<span class="hlt">AAr</span>.2r, C6Br, C7Ar, and C8n.1n at Site U1334. Subchron C5Dr.1n (~17.5 Ma) is recorded at both sites, supporting its apparent recording in the South Atlantic Ocean, and has an estimated duration of ~40 kyr. The Oligocene-Miocene calcareous oozes have magnetizations carried by submicron magnetite, as indicated by thermal demagnetization of magnetic remanences, the anhysteretic remanence to susceptibility ratio, and magnetic hysteresis parameters. Transmission electron microscopy of magnetic separates indicates the presence of low-titanium iron oxide (magnetite) grains with size (50-100 nm) and shape similar to modern and fossil bacterial magnetite, supporting other evidence that biogenic submicron magnetite is the principal remanence carrier in these sediments. In the equatorial Pacific Ocean, low organic-carbon burial arrests microbial pore-water sulfate reduction, thereby aiding preservation of bacterial magnetite.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/19960039926','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19960039926"><span>Investigation of source location determination from Magsat magnetic anomalies: The Euler method approach</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Ravat, Dhananjay</p> <p>1996-01-01</p> <p>The applicability of the Euler method of source location determination was investigated on several model situations pertinent to satellite-data scale situations as well as Magsat data of Europe. Our investigations enabled us to understand the end-member cases for which the Euler method will work with the present satellite magnetic data and also the cases for which the assumptions implicit in the Euler method will not be met by the present satellite magnetic data. These results have been presented in one invited lecture at the Indo-US workshop on Geomagnetism in Studies of the Earth's Interior in August 1994 in Pune, India, and at one presentation at the 21st General Assembly of the IUGG in July 1995 in Boulder, CO. A new method, called Anomaly Attenuation Rate (<span class="hlt">AAR</span>) Method (based on the Euler method), was developed during this study. This method is scale-independent and is appropriate to locate centroids of semi-compact three dimensional sources of gravity and magnetic anomalies. The method was presented during 1996 Spring AGU meeting and a manuscript describing this method is being prepared for its submission to a high-ranking journal. The grant has resulted in 3 papers and presentations at national and international meetings and one manuscript of a paper (to be submitted shortly to a reputable journal).</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017APS..MAR.M1363R','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017APS..MAR.M1363R"><span>Energetics and Kinetics of trans-SNARE Zippering</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Rebane, Aleksander A.; Shu, Tong; Krishnakumar, Shyam; Rothman, James E.; Zhang, Yongli</p> <p></p> <p>Synaptic exocytosis relies on assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins into a four-helix bundle to drive membrane fusion. Complementary SNAREs anchored to the synaptic vesicle (v-SNARE) and the plasma membrane (t-SNARE) associate from their N-termini, transiting a half-assembled intermediate (trans-SNARE), and ending at their C-termini with a rapid power stroke that leads to membrane fusion. Although cytosolic SNARE assembly has been characterized, it remains unknown how membranes modulate the energetics and kinetics of SNARE assembly. Here, we present optical tweezers measurements on folding of single membrane proteins in phospholipid bilayers. To our knowledge, this is the first such report. We measured the energetics, kinetics, and assembly intermediates of trans-SNAREs formed between a t-SNARE inserted into a bead-supported bilayer and a v-SNARE in a nanodisc. We found that the repulsive force of the apposed membranes increases the lifetime of the half-assembled intermediate. Our findings provide a single-molecule platform to study the regulation of trans-SNARE assembly by proteins that act on the half-assembled state, and thus reveal the mechanistic basis of the speed and high fidelity of synaptic transmission. This work was supported by US National Institutes of Health Grants F31 GM119312-01 (to <span class="hlt">A.A.R</span>) and R01 GM093341 (to Y.Z.).</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28334938','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28334938"><span>Clinical and genetic characterization of leukoencephalopathies in adults.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lynch, David S; Rodrigues Brandão de Paiva, Anderson; Zhang, Wei Jia; Bugiardini, Enrico; Freua, Fernando; Tavares Lucato, Leandro; Macedo-Souza, Lucia Inês; Lakshmanan, Rahul; Kinsella, Justin A; Merwick, Aine; Rossor, Alexander M; Bajaj, Nin; Herron, Brian; McMonagle, Paul; Morrison, Patrick J; Hughes, Deborah; Pittman, Alan; Laurà, Matilde; Reilly, Mary M; Warren, Jason D; Mummery, Catherine J; Schott, Jonathan M; Adams, Matthew; Fox, Nick C; Murphy, Elaine; Davagnanam, Indran; Kok, Fernando; Chataway, Jeremy; Houlden, Henry</p> <p>2017-05-01</p> <p>Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and radiological presentations. For these reasons, patients with genetic leukoencephalopathies often endure a long diagnostic odyssey before receiving a definitive diagnosis or may receive no diagnosis at all. In this study, we used focused and whole exome sequencing to evaluate a cohort of undiagnosed adult patients referred to a specialist leukoencephalopathy service. In total, 100 patients were evaluated using focused exome sequencing of 6100 genes. We detected pathogenic or likely pathogenic variants in 26 cases. The most frequently mutated genes were NOTCH3, EIF2B5, <span class="hlt">AARS</span>2 and CSF1R. We then carried out whole exome sequencing on the remaining negative cases including four family trios, but could not identify any further potentially disease-causing mutations, confirming the equivalence of focused and whole exome sequencing in the diagnosis of genetic leukoencephalopathies. Here we provide an overview of the clinical and genetic features of these disorders in adults. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018MRE.....5d6520G','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018MRE.....5d6520G"><span>Study on elevated-temperature flow behavior of Ni-Cr-Mo-B ultra-heavy-plate steel via experiment and modelling</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Gao, Zhi-yu; Kang, Yu; Li, Yan-shuai; Meng, Chao; Pan, Tao</p> <p>2018-04-01</p> <p>Elevated-temperature flow behavior of a novel Ni-Cr-Mo-B ultra-heavy-plate steel was investigated by conducting hot compressive deformation tests on a Gleeble-3800 thermo-mechanical simulator at a temperature range of 1123 K–1423 K with a strain rate range from 0.01 s‑1 to10 s‑1 and a height reduction of 70%. Based on the experimental results, classic strain-compensated Arrhenius-type, a new revised strain-compensated Arrhenius-type and classic modified Johnson-Cook constitutive models were developed for predicting the high-temperature deformation behavior of the steel. The predictability of these models were comparatively evaluated in terms of statistical parameters including correlation coefficient (R), average absolute relative error (<span class="hlt">AARE</span>), average root mean square error (RMSE), normalized mean bias error (NMBE) and relative error. The statistical results indicate that the new revised strain-compensated Arrhenius-type model could give prediction of elevated-temperature flow stress for the steel accurately under the entire process conditions. However, the predicted values by the classic modified Johnson-Cook model could not agree well with the experimental values, and the classic strain-compensated Arrhenius-type model could track the deformation behavior more accurately compared with the modified Johnson-Cook model, but less accurately with the new revised strain-compensated Arrhenius-type model. In addition, reasons of differences in predictability of these models were discussed in detail.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017EGUGA..1911741J','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017EGUGA..1911741J"><span>A new long sediment record from Padul, southern Spain records orbital- and suborbital-scale environmental and climate changes during the middle and late Quaternary</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Jimenez-Moreno, Gonzalo; Camuera, Jon; Ramos-Roman, Maria J.; Toney, Jaime L.; Anderson, R. Scott; Jimenez-Espejo, Francisco J.; Kaufman, Darrell; Bright, Jordon; Webster, Cole</p> <p>2017-04-01</p> <p>Long paleoenvironmental records are necessary in order to understand recurrent climatic or paleoenvironmental changes occurring with a certain periodicity (i.e., glacial-interglacial cycles). In this respect, the Padul peat bog has one of the best available records of Pleistocene sediments in semiarid Southern Europe. The sedimentary sequence is more than 100 m thick and has been used to study palaeoenvironmental change for the past ca. 1 Ma. Since the 1960s several cores have already been taken from this basin showing oscillations in many proxies (pollen, organic geochemistry and sedimentation) related with paleoclimatic and paleohydrological changes. However, a more detailed and higher resolution study, using new dating and analytical techniques (AMS 14C, <span class="hlt">AAR</span>, continuous XRF-scanning, high-resolution pollen analysis and geochemistry), needs to be done in such an interesting site. Here we present preliminary paleoenvironmental data from a new sediment core, Padul-15-05, which shows significant changes in the environment and lake sedimentation, probably related with glacial-interglacial climate dynamics during the past ca. 300,000 years. These data confirm that orbital- as well as suborbital-scale variability (i.e., Heinrich, D-O events) are recorded in the studied core. This unique record thus has very high potential for paleoenvironmental and paleoclimatic reconstructions for, at least, the two last climatic cycles in this semiarid Mediterranean area.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017EGUGA..19..966R','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017EGUGA..19..966R"><span>Observed Changes in the Himalayan Glaciers: Multiple Driving Factors</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Romshoo, Shakil; Rashid, Irfan; Abdullah, Tariq; Fayaz, Midhat</p> <p>2017-04-01</p> <p>There is lack of credible knowledge about Himalayan cryosphere as is evident from the contradictory reports about the status of the glaciers in the region. Glacier behavior in Himalaya has to be understood and interpreted in light of the multiple driving factors; topography, climate and anthropocene. The observed changes in Himalayan glaciers, determined by studying a few hundred glaciers in the Himalaya, indicated that the glacier response varies across different ranges. Satellite images (1990-2015), DEM, altimetry data supported by selective field campaigns, were used to map the changes in glacier boundaries, snout, ELA, <span class="hlt">AAR</span>, volume, thickness, debris cover and several other glacier parameters. The glaciers across the six ranges of Pir Panjal (PR), Greater Himalaya (GH), Shamasbari (SR), Zanaskar (ZR), Leh (LR) and Karakorum (KR) showed quite varied changes. It was observed that the glaciers in the KR show the least glacial area recession (1.59%) primarily due to the extreme cold winters with -18oC average temperature. Other glacial parameters like snout, ELA, <span class="hlt">AAR</span> and glacier volume also showed very little changes in the KR during the period. The glaciers in the LR, with an average winter temperature of -6o C, have shrunk, on an average, by 4.19 % during the period, followed by the glaciers in the ZR showing a loss of 5.46%. The highest glacier retreat of 7.72% and 6.94% was observed in the GH and SR with the average winter temperature of -1.3oc and -6.2oc respectively. In the PR, almost all the glaciers have vanished during the last 6-7 decades due to the increasing winter temperatures. The glaciers in the Kashmir showed an overall recession of 26.40% in area which is one of the highest reported for the Himalayan glaciers. The glaciers in the valley showed the maximum reduction in thickness (2.56m) using the IceSat data from 2000-08 while as the Karakoram glaciers showed the least reduction in thickness (0.53m). It was found that the maximum recession of glacial</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2013EGUGA..15.7469P','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2013EGUGA..15.7469P"><span>Evaluating flow laws for dynamically recrystallized quartz based on field data</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Peters, Max; Herwegh, Marco</p> <p>2013-04-01</p> <p>The extrapolation of experimentally controlled deformation conditions, and the resulting relations between physical parameters acting during ductile deformation, to nature is considered controversial (see Herwegh et al., 2005 and references therein). Whereas the relationship between flow stress and recrystallized grain size can be empirically derived from lab experiments using paleopiezometers (e.g. Stipp & Tullis, 2003), the relation between recrystallized grain size, strain rate, differential stress, temperature and activation energy for dislocation creep requires further constraints. For these relations, various power law flow laws for dynamically recrystallized quartz were proposed over the past years (Paterson & Luan, 1990; Luan & Paterson, 1992; Gleason & Tullis, 1995; Hirth et al., 2001, Rutter & Brodie, 2004). The variations in the flow laws are mainly characterized by different starting materials, experimental conditions, the activation energy for dislocation creep and the stress exponent n. In this study we compare and evaluate experimentally derived flow laws regarding their reliability for the prediction of rheology of background deformation of naturally deformed crystalline samples from mylonites of the <span class="hlt">Aar</span> massif (Swiss Central Alps). The majority of samples comprises highly deformed rocks (e.g. Central <span class="hlt">Aare</span> granite), which exhibit severe grain size reduction. This reduction dominantly occurred by subgrain rotation (SGR), in the case of low temperature overprint by bulging recrystallization (BLG). Towards elevated temperatures, grain boundary migration (GBM) and SGR recrystallization were active. Along the metamorphic gradient (300 - 475°C) quartz microstructures and associated recrystallized grain size distributions indicate steady state mean grain sizes. The quantification of the metamorphic gradient (temperature, pressure, water fugacity) over the sampling area allowed the application of flow laws, yielding variations of 6 orders of magnitude in</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018HESS...22...31R','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018HESS...22...31R"><span>Tributaries affect the thermal response of lakes to climate change</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Råman Vinnå, Love; Wüest, Alfred; Zappa, Massimiliano; Fink, Gabriel; Bouffard, Damien</p> <p>2018-01-01</p> <p>Thermal responses of inland waters to climate change varies on global and regional scales. The extent of warming is determined by system-specific characteristics such as fluvial input. Here we examine the impact of ongoing climate change on two alpine tributaries, the <span class="hlt">Aare</span> River and the Rhône River, and their respective downstream peri-alpine lakes: Lake Biel and Lake Geneva. We propagate regional atmospheric temperature effects into river discharge projections. These, together with anthropogenic heat sources, are in turn incorporated into simple and efficient deterministic models that predict future water temperatures, river-borne suspended sediment concentration (SSC), lake stratification and river intrusion depth/volume in the lakes. Climate-induced shifts in river discharge regimes, including seasonal flow variations, act as positive and negative feedbacks in influencing river water temperature and SSC. Differences in temperature and heating regimes between rivers and lakes in turn result in large seasonal shifts in warming of downstream lakes. The extent of this repressive effect on warming is controlled by the lakes hydraulic residence time. Previous studies suggest that climate change will diminish deep-water oxygen renewal in lakes. We find that climate-related seasonal variations in river temperatures and SSC shift deep penetrating river intrusions from summer towards winter. Thus potentially counteracting the otherwise negative effects associated with climate change on deep-water oxygen content. Our findings provide a template for evaluating the response of similar hydrologic systems to on-going climate change.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10582558','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10582558"><span>Effects of the pesticide amitraz and its metabolite BTS 27271 on insulin and glucagon secretion from the perfused rat pancreas: involvement of alpha2D-adrenergic receptors.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Abu-Basha, E A; Yibchok-Anun, S; Hopper, D L; Hsu, W H</p> <p>1999-11-01</p> <p>The study purpose was to investigate the direct effect of amitraz, a formamidine insecticide/acaricide, and its active metabolite BTS 27271 on insulin and glucagon secretion from the perfused rat pancreas. Amitraz and BTS 27271 (0.01, 0.1, 1, and 10 micromol/L) inhibited insulin secretion in a concentration-dependent manner. Amitraz increased glucagon secretion at 10 micromol/L, whereas BTS 27271 increased glucagon secretion at 1 and 10 micromol/L. Amitraz- and BTS 27271-induced decreases in insulin secretion and increases in glucagon secretion were not abolished during the 10-minute washout period. During the arginine treatment, both amitraz and BTS 27271 groups (0.1, 1, and 10 micromol/L) had lower insulin secretion and higher glucagon secretion than the control group. Idazoxan, an alpha2A/2D-adrenergic receptor (AR) antagonist, prevented the inhibitory effect of amitraz on insulin secretion in a concentration-dependent manner, but prazosin, an alpha1- and alpha2B/2C-AR antagonist, failed to antagonize the effect of amitraz. These results demonstrate that (1) amitraz and BTS 27271 inhibit insulin and stimulate glucagon secretion from the perfused rat pancreas, (2) amitraz inhibits insulin secretion by activation of alpha2D-ARs, since rats have alpha2D- but not alpha2<span class="hlt">A-ARs</span>, and (3) amitraz and BTS 27271 may have a high binding affinity to the alpha2D-ARs of pancreatic islets.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018JSeis..22..353K','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018JSeis..22..353K"><span>Nonlinear time series modeling and forecasting the seismic data of the Hindu Kush region</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Khan, Muhammad Yousaf; Mittnik, Stefan</p> <p>2018-01-01</p> <p>In this study, we extended the application of linear and nonlinear time models in the field of earthquake seismology and examined the out-of-sample forecast accuracy of linear Autoregressive (AR), Autoregressive Conditional Duration (ACD), Self-Exciting Threshold Autoregressive (SETAR), Threshold Autoregressive (TAR), Logistic Smooth Transition Autoregressive (LSTAR), Additive Autoregressive (<span class="hlt">AAR</span>), and Artificial Neural Network (ANN) models for seismic data of the Hindu Kush region. We also extended the previous studies by using Vector Autoregressive (VAR) and Threshold Vector Autoregressive (TVAR) models and compared their forecasting accuracy with linear AR model. Unlike previous studies that typically consider the threshold model specifications by using internal threshold variable, we specified these models with external transition variables and compared their out-of-sample forecasting performance with the linear benchmark AR model. The modeling results show that time series models used in the present study are capable of capturing the dynamic structure present in the seismic data. The point forecast results indicate that the AR model generally outperforms the nonlinear models. However, in some cases, threshold models with external threshold variables specification produce more accurate forecasts, indicating that specification of threshold time series models is of crucial importance. For raw seismic data, the ACD model does not show an improved out-of-sample forecasting performance over the linear AR model. The results indicate that the AR model is the best forecasting device to model and forecast the raw seismic data of the Hindu Kush region.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27769108','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27769108"><span>Fibro markers for prediction of hepatocellular carcinoma in Egyptian patients with chronic liver disease.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mobarak, Lamiaa; Omran, Dalia; Nabeel, Mohammed M; Zakaria, Zeinab</p> <p>2017-06-01</p> <p>It is well known that hepatocellular carcinoma (HCC) develops as a consequence of hepatic fibrosis progression. In this study, we aimed to evaluate the inflammatory and fibrosis markers as predictors for HCC development among patients with hepatitis C virus (HCV) related chronic liver disease to help in early diagnosis and management of HCC. A total of 280 patients with chronic liver disease were included in this retrospective study, out of them 140 had liver cirrhosis with HCC and 140 had cirrhosis without HCC. Eight readily available blood indices King score, Fibro Q, AST-ALT ratio (<span class="hlt">AAR</span>), APRI, LOK index, Goteborg University Cirrhosis Index (GUCI), fibro alpha, and Biotechnology Research Center (BRC) were constructed to compare the accuracies of these non invasive scores in predicting HCC development. All fibrosis scores except APRI were significantly higher in HCC. We found that Fibro alpha and BRC had superior diagnostic performance in prediction of HCC based on area under curve of 0.91 and 0.93, respectively compared to other scores with area under curve ranged from poor to failure (0.59-0.66). Almost all cirrhotic cases were secondary to HCV (93.6%), while HBV was detected in 2.1% of cases only. Anti-HCV positive was reported in 100% of HCC cases (P = 0.002). Fibro alpha and BRC scores can be used for prediction of HCC. J. Med. Virol. 89:1062-1068, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li class="active"><span>25</span></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_25 --> <div class="footer-extlink text-muted" style="margin-bottom:1rem; text-align:center;">Some links on this page may take you to non-federal websites. 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