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Sample records for results phase iva

  1. Effects of induction docetaxel, platinum, and fluorouracil chemotherapy in patients with stage III or IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: Final results of 2 parallel phase 2 clinical trials.

    PubMed

    Kong, Lin; Zhang, Youwang; Hu, Chaosu; Guo, Ye; Lu, Jiade J

    2017-06-15

    The effects of docetaxel, platinum, and fluorouracil (TPF) induction chemotherapy plus concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal cancer (NPC) are unclear. This study examined the long-term outcomes of the addition of this regimen to CCRT for stage III and IVA/B NPC. Two parallel, single-arm phase 2 trials were performed synchronously to evaluate the efficacy and toxicity of TPF-based induction chemotherapy in patients with stage III or IVA/B NPC. The induction chemotherapy, which preceded standard intensity-modulated radiation therapy/platinum-based chemoradiation, consisted of 3 cycles of docetaxel (75 mg/m(2) on day 1), cisplatin (75 mg/m(2) on day 1), and a continuous infusion of fluorouracil (500 mg/m(2) /d on days 1-5) every 4 weeks. The primary endpoint for both trials was 5-year overall survival (OS). Between January 2007 and July 2010, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued to the 2 trials. With a median follow-up of 67 months, the 5-year OS, progression-free survival, distant metastasis-free survival, and local progression-free survival (LPFS) rates were all improved in comparison with historical benchmarks for patients with stage III or IVA/IVB NPC. Multivariate analyses indicated that T and N classifications (T1/T2 vs T3/T4 and N3 vs N0-N2) were the only significant prognosticators for OS. The number of induction chemotherapy cycles was the only significant prognostic factor for predicting LPFS. TPF-based induction chemotherapy appears to significantly improve outcomes in comparison with historical data when it is administered before CCRT for locoregionally advanced NPC. A phase 3 trial is currently being performed to confirm this benefit. Cancer 2017;123:2258-2267. © 2017 American Cancer Society. © 2017 American Cancer Society.

  2. Diagnosing mucopolysaccharidosis IVA.

    PubMed

    Wood, Timothy C; Harvey, Katie; Beck, Michael; Burin, Maira Graeff; Chien, Yin-Hsiu; Church, Heather J; D'Almeida, Vânia; van Diggelen, Otto P; Fietz, Michael; Giugliani, Roberto; Harmatz, Paul; Hawley, Sara M; Hwu, Wuh-Liang; Ketteridge, David; Lukacs, Zoltan; Miller, Nicole; Pasquali, Marzia; Schenone, Andrea; Thompson, Jerry N; Tylee, Karen; Yu, Chunli; Hendriksz, Christian J

    2013-03-01

    Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity. Diagnosis can be challenging and requires agreement of clinical, radiographic, and laboratory findings. A group of biochemical genetics laboratory directors and clinicians involved in the diagnosis of MPS IVA, convened by BioMarin Pharmaceutical Inc., met to develop recommendations for diagnosis. The following conclusions were reached. Due to the wide variation and subtleties of radiographic findings, imaging of multiple body regions is recommended. Urinary glycosaminoglycan analysis is particularly problematic for MPS IVA and it is strongly recommended to proceed to enzyme activity testing even if urine appears normal when there is clinical suspicion of MPS IVA. Enzyme activity testing of GALNS is essential in diagnosing MPS IVA. Additional analyses to confirm sample integrity and rule out MPS IVB, multiple sulfatase deficiency, and mucolipidoses types II/III are critical as part of enzyme activity testing. Leukocytes or cultured dermal fibroblasts are strongly recommended for enzyme activity testing to confirm screening results. Molecular testing may also be used to confirm the diagnosis in many patients. However, two known or probable causative mutations may not be identified in all cases of MPS IVA. A diagnostic testing algorithm is presented which attempts to streamline this complex testing process.

  3. Mucopolysaccharidosis IVA and glycosaminoglycans

    PubMed Central

    Khan, Shaukat; Alméciga-Díaz, Carlos J.; Sawamoto, Kazuki; Mackenzie, William G.; Theroux, Mary C; Pizarro, Christian; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

    2016-01-01

    Mucopolysaccharidosis IVA (MPS IVA; Morquio A: OMIM 253000) is a lysosomal storage disease with an autosomal recessive trait caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of specific glycosaminoglycans (GAGs): chondroitin-6-sulfate (C6S) and keratan sulfate (KS). C6S and KS are mainly produced in the cartilage. Therefore, the undegraded substrates are stored primarily in cartilage and in its extracellular matrix (ECM), leading to a direct impact on cartilage and bone development, and successive systemic skeletal dysplasia. Chondrogenesis, the earliest phase of skeletal formation, is maintained by cellular interactions with the ECM, growth and differentiation factors, signaling pathways, and transcription factors in a temporal-spatial manner. In patients with MPS IVA, the cartilage is disrupted at birth as a consequence of abnormal chondrogenesis and/or endochondral ossification. The unique skeletal features are distinguished by a disproportional short stature, odontoid hypoplasia, spinal cord compression, tracheal obstruction, pectus carinatum, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. In spite of many descriptions of these unique clinical features, delay of diagnosis still happens. The pathogenesis and treatment of systemic skeletal dysplasia in MPS IVA remains an unmet challenge. In this review article, we comprehensively describe historical aspect, property of GAGs, diagnosis, screening, pathogenesis, and current and future therapies of MPS IVA. PMID:27979613

  4. Mucopolysaccharidosis IVA and glycosaminoglycans.

    PubMed

    Khan, Shaukat; Alméciga-Díaz, Carlos J; Sawamoto, Kazuki; Mackenzie, William G; Theroux, Mary C; Pizarro, Christian; Mason, Robert W; Orii, Tadao; Tomatsu, Shunji

    Mucopolysaccharidosis IVA (MPS IVA; Morquio A: OMIM 253000) is a lysosomal storage disease with an autosomal recessive trait caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of specific glycosaminoglycans (GAGs): chondroitin-6-sulfate (C6S) and keratan sulfate (KS). C6S and KS are mainly produced in the cartilage. Therefore, the undegraded substrates are stored primarily in cartilage and in its extracellular matrix (ECM), leading to a direct impact on cartilage and bone development, and successive systemic skeletal dysplasia. Chondrogenesis, the earliest phase of skeletal formation, is maintained by cellular interactions with the ECM, growth and differentiation factors, signaling pathways, and transcription factors in a temporal-spatial manner. In patients with MPS IVA, the cartilage is disrupted at birth as a consequence of abnormal chondrogenesis and/or endochondral ossification. The unique skeletal features are distinguished by a disproportional short stature, odontoid hypoplasia, spinal cord compression, tracheal obstruction, pectus carinatum, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. In spite of many descriptions of these unique clinical features, delay of diagnosis still happens. The pathogenesis and treatment of systemic skeletal dysplasia in MPS IVA remains an unmet challenge. In this review article, we comprehensively describe historical aspect, property of GAGs, diagnosis, screening, pathogenesis, and current and future therapies of MPS IVA. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Cervical Cancer Stage IVA

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IVA Add to My Pictures View / ... 1575x1200 View Download Large: 3150x2400 View Download Title: Cervical Cancer Stage IVA Description: Stage IVA cervical cancer; ...

  6. Metallographic Cooling Rate of IVA Irons Revisited

    NASA Technical Reports Server (NTRS)

    Yang, J.; Goldstein, J. I.; Scott, E. R. D.

    2005-01-01

    There is long standing problem reconciling the chemical evidence that the IVA iron meteorites formed in a core with the diverse cooling rates reported by several researchers. This large inferred range of cooling rates suggests that the IVA irons were distributed at different depths in a parent body with a complex structure when the Widmanstatten pattern formed. On the other hand, some researchers argued that the diverse cooling rates in group IVA result from inaccurate model parameters such as phase diagram, interdiffusion coefficients, and kamacite nucleation and growth mechanisms. In addition, the measured cooling rates may not apply for the same cooling temperature ranges, and the variation in the crystallographic orientations of the Widmanstatten plates on the analysis surface may result in inaccurate measurements of widths needed for the computer simulation models. We have revaluated the major parameters in computer model developed by Hopfe and Goldstein and measured cooling rates for the IVA irons. Such data are useful in evaluating whether these meteorites were part of a single core of a parent body during the formation of the Widmanstatten pattern.

  7. Conversion of IVA Human Computer Model to EVA Use and Evaluation and Comparison of the Result to Existing EVA Models

    NASA Technical Reports Server (NTRS)

    Hamilton, George S.; Williams, Jermaine C.

    1998-01-01

    This paper describes the methods, rationale, and comparative results of the conversion of an intravehicular (IVA) 3D human computer model (HCM) to extravehicular (EVA) use and compares the converted model to an existing model on another computer platform. The task of accurately modeling a spacesuited human figure in software is daunting: the suit restricts the human's joint range of motion (ROM) and does not have joints collocated with human joints. The modeling of the variety of materials needed to construct a space suit (e. g. metal bearings, rigid fiberglass torso, flexible cloth limbs and rubber coated gloves) attached to a human figure is currently out of reach of desktop computer hardware and software. Therefore a simplified approach was taken. The HCM's body parts were enlarged and the joint ROM was restricted to match the existing spacesuit model. This basic approach could be used to model other restrictive environments in industry such as chemical or fire protective clothing. In summary, the approach provides a moderate fidelity, usable tool which will run on current notebook computers.

  8. Conversion of IVA Human Computer Model to EVA Use and Evaluation and Comparison of the Result to Existing EVA Models

    NASA Technical Reports Server (NTRS)

    Hamilton, George S.; Williams, Jermaine C.

    1998-01-01

    This paper describes the methods, rationale, and comparative results of the conversion of an intravehicular (IVA) 3D human computer model (HCM) to extravehicular (EVA) use and compares the converted model to an existing model on another computer platform. The task of accurately modeling a spacesuited human figure in software is daunting: the suit restricts the human's joint range of motion (ROM) and does not have joints collocated with human joints. The modeling of the variety of materials needed to construct a space suit (e. g. metal bearings, rigid fiberglass torso, flexible cloth limbs and rubber coated gloves) attached to a human figure is currently out of reach of desktop computer hardware and software. Therefore a simplified approach was taken. The HCM's body parts were enlarged and the joint ROM was restricted to match the existing spacesuit model. This basic approach could be used to model other restrictive environments in industry such as chemical or fire protective clothing. In summary, the approach provides a moderate fidelity, usable tool which will run on current notebook computers.

  9. Elosulfase Alfa: a review of its use in patients with mucopolysaccharidosis type IVA (Morquio A syndrome).

    PubMed

    Lyseng-Williamson, Katherine A

    2014-10-01

    Elosulfase alfa (Vimizim(®)) is a recombinant form of the human lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS) that is lacking in patients with mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome). It is the first, and currently only, disease-specific treatment option for this very rare, progressively degenerative, autosomal-recessive lysosomal storage disorder. Enzyme replacement therapy with elosulfase alfa aims to restore GALNS activity, thereby preventing the accumulation of keratan sulfate (KS) and chondroitin-6-sulfate in lysosomal compartments of cells that results in the clinical manifestations of MPS IVA. In clinical trials in children and adults with MPS IVA, intravenous elosulfase alfa 2 mg/kg/week provided significant and sustained improvements in urinary levels of KS (a pharmacodynamic biomarker for the disease). In the key placebo-controlled, 24-week, phase 3 trial in patients with MPS IVA aged ≥5 years, elosulfase alfa 2 mg/kg/week significantly improved endurance [least squares mean placebo-adjusted change from baseline in 6-min walk test distance 22.5 m (95 % CI 4.0-40.9)]. Infusion-associated reactions, the primary tolerability issue associated with elosulfase alfa, are generally mild to moderate in severity, self-limiting, and manageable. In the absence of a cure, GALNS enzyme replacement therapy with elosulfase alfa is an important achievement in the treatment of MPS IVA.

  10. IVA robotics for Space Station Freedom

    NASA Technical Reports Server (NTRS)

    Jones, Sharon Monica

    1992-01-01

    The objective is to increase the scientific productivity of Space Station Freedom (Spacelab) during the man-tended phase and beyond. The topics are presented in viewgraph form and include: Space Station Freedom (SSF) background, man-tended phase, intra-vehicular activity (IVA) robotics, protein crystal growth experiment, thermal enclosure system equipment, and candidate mockup demonstrations.

  11. IVA robotics for Space Station Freedom

    NASA Technical Reports Server (NTRS)

    Jones, Sharon Monica

    1992-01-01

    The objective is to increase the scientific productivity of Space Station Freedom (Spacelab) during the man-tended phase and beyond. The topics are presented in viewgraph form and include: Space Station Freedom (SSF) background, man-tended phase, intra-vehicular activity (IVA) robotics, protein crystal growth experiment, thermal enclosure system equipment, and candidate mockup demonstrations.

  12. Genetic dissection of DivIVA functions in Listeria monocytogenes.

    PubMed

    Kaval, Karan Gautam; Hauf, Samuel; Rismondo, Jeanine; Hahn, Birgitt; Halbedel, Sven

    2017-10-02

    DivIVA is a membrane binding protein that clusters at curved membrane regions such as the cell poles and the membrane invaginations occurring during cell division. DivIVA proteins recruit many other proteins to these subcellular sites through direct protein-protein interactions. DivIVA-dependent functions are typically associated with cell growth and division, even though species-specific differences in the spectrum of DivIVA functions and their causative interaction partners exist. DivIVA from the Gram-positive human pathogen Listeria monocytogenes has at least three different functions. In this bacterium, DivIVA is required for precise positioning of the septum at mid-cell, it contributes to secretion of autolysins required for breakdown of peptidoglycan at the septum after completion of cell division, and it is essential for flagellar motility. While the DivIVA interaction partners for control of division site selection are well-established, the proteins connecting DivIVA with autolysin secretion or swarming motility are completely unknown. We set out to identify divIVA alleles, in which these three DivIVA functions could be separated, since the question of the degree to which the three functions of L. monocytogenes DivIVA are interlinked could not be answered before. Here, we identify such alleles, and our results show that division site selection, autolysin secretion, and swarming represent three discrete pathways that are independently influenced by DivIVA. These findings provide the required basis for the identification of DivIVA interaction partners controlling autolysin secretion and swarming in the future.IMPORTANCE DivIVA of the pathogenic bacterium Listeria monocytogenes is a central scaffold protein that influences at least three different cellular processes, namely cell division, protein secretion and bacterial motility. How DivIVA coordinates these rather unrelated processes is not known. We here identify variants of L. monocytogenes DivIVA, in which

  13. Enzyme replacement therapy for treating mucopolysaccharidosis type IVA (Morquio A syndrome): effect and limitations

    PubMed Central

    Tomatsu, Shunji; Sawamoto, Kazuki; Shimada, Tsutomu; Bober, Michael B.; Kubaski, Francyne; Yasuda, Eriko; Mason, Robert W.; Khan, Shaukat; Alméciga-Díaz, Carlos J.; Barrera, Luis A.; Mackenzie, William G.

    2015-01-01

    Introduction Following a Phase III, randomized, double-blind, placebo (PBO)-controlled, multinational study in subjects with mucopolysaccharidosis IVA (MPS IVA), enzyme replacement therapy (ERT) of elosulfase alfa has been approved in several countries. The study was designed to evaluate safety and efficacy of elosulfase alfa in patients with MPS IVA aged 5 years and older. Areas covered Outcomes of clinical trials for MPS IVA have been described. Subjects received either 2.0 mg/kg/week, 2.0 mg/kg/every other week, or PBO, for 24 weeks. The primary endpoint was the change from baseline 6-min walk test (6MWT) distance compared to PBO. The 6MWT results improved in patients receiving 2 mg/kg weekly compared to PBO. The every other week regimen resulted in walk distances comparable to PBO. There was no change from baseline in the 3 Min Stair Climb Test in both treatment groups. Following completion of the initial study, patients, who continued to receive elosulfase alfa 2 mg/kg weekly (QW) for another 48 weeks (for a total of up to 72-week exposure), did not show additional improvement on 6MWT. Expert opinion We suggest that ERT is a therapeutic option for MPS IVA, providing a modest effect and the majority of the effects are seen in the soft tissues. PMID:26973801

  14. Enzyme replacement therapy for treating mucopolysaccharidosis type IVA (Morquio A syndrome): effect and limitations.

    PubMed

    Tomatsu, Shunji; Sawamoto, Kazuki; Shimada, Tsutomu; Bober, Michael B; Kubaski, Francyne; Yasuda, Eriko; Mason, Robert W; Khan, Shaukat; Alméciga-Díaz, Carlos J; Barrera, Luis A; Mackenzie, William G; Orii, Tadao

    2015-11-01

    Following a Phase III, randomized, double-blind, placebo (PBO)-controlled, multinational study in subjects with mucopolysaccharidosis IVA (MPS IVA), enzyme replacement therapy (ERT) of elosulfase alfa has been approved in several countries. The study was designed to evaluate safety and efficacy of elosulfase alfa in patients with MPS IVA aged 5 years and older. Outcomes of clinical trials for MPS IVA have been described. Subjects received either 2.0 mg/kg/week, 2.0 mg/kg/every other week, or PBO, for 24 weeks. The primary endpoint was the change from baseline 6-min walk test (6MWT) distance compared to PBO. The 6MWT results improved in patients receiving 2 mg/kg weekly compared to PBO. The every other week regimen resulted in walk distances comparable to PBO. There was no change from baseline in the 3 Min Stair Climb Test in both treatment groups. Following completion of the initial study, patients, who continued to receive elosulfase alfa 2 mg/kg weekly (QW) for another 48 weeks (for a total of up to 72-week exposure), did not show additional improvement on 6MWT. We suggest that ERT is a therapeutic option for MPS IVA, providing a modest effect and the majority of the effects are seen in the soft tissues.

  15. Cooling rates of group IVA iron meteorites

    NASA Technical Reports Server (NTRS)

    Willis, J.; Wasson, J. T.

    1978-01-01

    Cooling rates of six group IVA iron meteorites were estimated by a taenite central Ni concentration-taenite half-width method. Calculated cooling rates range from 13 to 25 C/Myr, with an average of 20 C/Myr. No correlation between cooling rate and bulk Ni content is observed, and the data appear to be consistent with a uniform cooling rate as expected from an igneous core origin. This result differs from previous studies reporting a wide range in cooling rates that were strongly correlated with bulk Ni content. The differences result mainly from differences in the phase diagram and the selected diffusion coefficients. Cooling rates inferred from taenite Ni concentrations at the interface with kamacite are consistent with those based on taenite central Ni content.

  16. Cooling rates of group IVA iron meteorites

    NASA Technical Reports Server (NTRS)

    Willis, J.; Wasson, J. T.

    1978-01-01

    Cooling rates of six group IVA iron meteorites were estimated by a taenite central Ni concentration-taenite half-width method. Calculated cooling rates range from 13 to 25 C/Myr, with an average of 20 C/Myr. No correlation between cooling rate and bulk Ni content is observed, and the data appear to be consistent with a uniform cooling rate as expected from an igneous core origin. This result differs from previous studies reporting a wide range in cooling rates that were strongly correlated with bulk Ni content. The differences result mainly from differences in the phase diagram and the selected diffusion coefficients. Cooling rates inferred from taenite Ni concentrations at the interface with kamacite are consistent with those based on taenite central Ni content.

  17. Mark IVA microprocessor support

    NASA Technical Reports Server (NTRS)

    Burford, A. L.

    1982-01-01

    The requirements and plans for the maintenance support of microprocessor-based controllers in the Deep Space Network Mark IVA System are discussed. Additional new interfaces and 16-bit processors have introduced problems not present in the Mark III System. The need for continuous training of maintenance personnel to maintain a level of expertise consistent with the sophistication of the required tools is also emphasized.

  18. Bone Marrow-sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin For Stage IB-IVA Cervical Cancer: An International Multicenter Phase II Clinical Trial (INTERTECC-2).

    PubMed

    Mell, Loren K; Sirák, Igor; Wei, Lichun; Tarnawski, Rafal; Mahantshetty, Umesh; Yashar, Catheryn M; McHale, Michael T; Xu, Ronghui; Honerkamp-Smith, Gordon; Carmona, Ruben; Wright, Mary; Williamson, Casey W; Kasaová, Linda; Li, Nan; Kry, Stephen; Michalski, Jeff; Bosch, Walter; Straube, William; Schwarz, Julie; Lowenstein, Jessica; Jiang, Steve B; Saenz, Cheryl C; Plaxe, Steve; Einck, John; Khorprasert, Chonlakiet; Koonings, Paul; Harrison, Terry; Shi, Mei; Mundt, A J

    2017-03-01

    To test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer. We enrolled patients with stage IB-IVA cervical carcinoma in a single-arm phase II trial involving 8 centers internationally. All patients received weekly cisplatin concurrently with once-daily IMRT, followed by intracavitary brachytherapy, as indicated. The primary endpoint was the occurrence of either acute grade ≥3 neutropenia or clinically significant GI toxicity within 30 days of completing chemoradiation therapy. A preplanned subgroup analysis tested the hypothesis that positron emission tomography-based image-guided IMRT (IG-IMRT) would lower the risk of acute neutropenia. We also longitudinally assessed patients' changes in quality of life. From October 2011 to April 2015, 83 patients met the eligibility criteria and initiated protocol therapy. The median follow-up was 26.0 months. The incidence of any primary event was 26.5% (95% confidence interval [CI] 18.2%-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (P=.012). The incidence of grade ≥3 neutropenia and clinically significant GI toxicity was 19.3% (95% CI 12.2%-29.0%) and 12.0% (95% CI 6.7%-20.8%), respectively. Compared with patients treated without IG-IMRT (n=48), those treated with IG-IMRT (n=35) had a significantly lower incidence of grade ≥3 neutropenia (8.6% vs 27.1%; 2-sided χ(2)P=.035) and nonsignificantly lower incidence of grade ≥3 leukopenia (25.7% vs 41.7%; P=.13) and any grade ≥3 hematologic toxicity (31.4% vs 43.8%; P=.25). IMRT reduces acute hematologic and GI toxicity compared with standard treatment, with promising therapeutic outcomes. Positron emission tomography IG-IMRT reduces the incidence of acute neutropenia. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Review of Clinical Presentation and Diagnosis of Mucopolysaccharidosis IVA

    PubMed Central

    Hendriksz, C.J.; Harmatz, P.; Beck, M.; Jones, S.; Wood, T.; Lachman, R.; Gravance, C.G.

    2013-01-01

    Mucopolysaccharidosis type IVA (MPS IVA) was described in 1929 by Luis Morquio from Uruguay and James Brailsford from England, and was later found as an autosomal recessive lysosomal storage disease. MPS IVA is caused by mutations in the gene encoding the enzyme, N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Reduced GALNS activity results in impaired catabolism of two glycosaminoglycans (GAGs), chondroitin-6-sulfate (C6S) and keratan sulfate (KS). Clinical presentations of MPS IVA reflect a spectrum of progression from a severe ”classical” phenotype to a mild “attenuated” phenotype. More than 180 different mutations have been identified in the GALNS gene, which likely explains the phenotypic heterogeneity of the disorder. Accumulation of C6S and KS manifests predominantly as short stature and skeletal dysplasia (dysostosis multiplex), including atlantoaxial instability and cervical cord compression. However, abnormalities in the visual, auditory, cardiovascular, and respiratory systems can also affect individuals with MPS IVA. Diagnosis is typically based on clinical examination, skeletal radiographs, urinary GAG, and enzymatic activity of GALNS in blood cells or fibroblasts. Deficiency of GALNS activity is a common assessment for the laboratory diagnosis of MPS IVA; however, with recently increased availability, gene sequencing for MPS IVA is often used to confirm enzyme results. As multiple clinical presentations are observed, diagnosis of MPS IVA may require multi-system considerations. This review provides a history of defining MPS IVA and how the understanding of the disease manifestations has changed over time. A summary of the accumulated knowledge is presented, including information from the International Morquio Registry. The classical phenotype is contrasted with attenuated cases, which are now being recognized and diagnosed more frequently. Laboratory based diagnoses of MPS IVA are also discussed. PMID:23665161

  20. Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA.

    PubMed

    Hendriksz, C J; Harmatz, P; Beck, M; Jones, S; Wood, T; Lachman, R; Gravance, C G; Orii, T; Tomatsu, S

    2013-01-01

    Mucopolysaccharidosis type IVA (MPS IVA) was described in 1929 by Luis Morquio from Uruguay and James Brailsford from England, and was later found as an autosomal recessive lysosomal storage disease. MPS IVA is caused by mutations in the gene encoding the enzyme, N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Reduced GALNS activity results in impaired catabolism of two glycosaminoglycans (GAGs), chondroitin-6-sulfate (C6S) and keratan sulfate (KS). Clinical presentations of MPS IVA reflect a spectrum of progression from a severe "classical" phenotype to a mild "attenuated" phenotype. More than 180 different mutations have been identified in the GALNS gene, which likely explains the phenotypic heterogeneity of the disorder. Accumulation of C6S and KS manifests predominantly as short stature and skeletal dysplasia (dysostosis multiplex), including atlantoaxial instability and cervical cord compression. However, abnormalities in the visual, auditory, cardiovascular, and respiratory systems can also affect individuals with MPS IVA. Diagnosis is typically based on clinical examination, skeletal radiographs, urinary GAG, and enzymatic activity of GALNS in blood cells or fibroblasts. Deficiency of GALNS activity is a common assessment for the laboratory diagnosis of MPS IVA; however, with recently increased availability, gene sequencing for MPS IVA is often used to confirm enzyme results. As multiple clinical presentations are observed, diagnosis of MPS IVA may require multi-system considerations. This review provides a history of defining MPS IVA and how the understanding of the disease manifestations has changed over time. A summary of the accumulated knowledge is presented, including information from the International Morquio Registry. The classical phenotype is contrasted with attenuated cases, which are now being recognized and diagnosed more frequently. Laboratory based diagnoses of MPS IVA are also discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. N-acetylglucosaminyltransferase IVa promotes invasion of choriocarcinoma.

    PubMed

    Nishino, Kimihiro; Yamamoto, Eiko; Niimi, Kaoru; Sekiya, Yoko; Yamashita, Yoriko; Kikkawa, Fumitaka

    2017-07-01

    Gestational trophoblastic neoplasia (GTN) results from the malignant transformation of placental trophoblasts which secrete human chorionic gonadotropin (hCG) as do normal placenta or hydatidiform mole. N-acetylglucosaminyltransferase IV (GnT-IV) is a glycosyltransferase which catalyses the formation of β1,4GlcNAc branches on the mannose core of N-glycans. Previous studies reported that β1,4GlcNAc branches on hCG were detected in GTN but not in normal pregnancy or hydatidiform mole. The aim of the present study was to understand the role of GnT-IVa in choriocarcinoma and find the target proteins for GnT-IVa glycosylation which contribute to the malignancy of choriocarcinoma. Immunohistochemistry showed that Griffonia simplicifolia lectin-II staining and GnT-IVa staining were intense in trophoblastic cells of invasive mole and choriocarcinoma. We established a choriocarcinoma cell line with GnT-IVa overexpression (Jar-GnT4a), and examined its malignant potential and target proteins for GnT-IVa glycosylation. GnT-IVa overexpression increased the cell migration and invasion (2.5- and 1.4-fold) as well as the ability to adhere to the extracellular matrix (ECM) components, including fibronectin and collagen type I and IV. The tumour formation potential of Jar-GnT4a in mice was significantly higher than that of control (P=0.0407), and the cumulative survival rate of mice with Jar-GnT4a was relatively lower than those with control. Immunoprecipitation studies showed that β1,4GlcNAc branches of N-glycans on integrin β1 in choriocarcinoma cells were increased by GnT-IVa overexpression. Nano-LC/MS/MS analysis suggested that lysosome-associated membrane glycoprotein 2 (LAMP-2) was a target protein for glycosylation by GnT-IVa. The increase in β1,4GlcNAc branches on LAMP-2 by GnT-IVa overexpression was confirmed by lectin blot analysis using whole cell lysate and conditioned medium. Our results suggest that highly branched N-glycans generated by the action of GnT-IVa

  2. Mucopolysaccharidosis IVA mutations in Chinese patients: 16 novel mutations.

    PubMed

    Wang, Zheng; Zhang, Weimin; Wang, Yun; Meng, Yan; Su, Liang; Shi, Huiping; Huang, Shangzhi

    2010-08-01

    Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disease caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS) and transmitted as an autosomal recessive trait. This is the first systematic mutation screen in Chinese MPS IVA patients. Mutation detections in 24 unrelated Chinese MPS IVA patients were performed by PCR and direct sequencing of exons or the mRNA of GALNS. A total of 42 mutant alleles were identified, belonging to 27 different mutations. Out of the 27 mutations, 16 were novel, including 2 splicing mutations (c.567-1G>T and c.634-1G>A), 2 nonsense mutations (p.W325X and p.Q422X) and 12 missense mutations (p.T88I, p.H142R, p.P163H, p.G168L, p.H236D, p.N289S, p.T312A, p.G316V, p.A324E, p.L366P, p.Q422K and p.F452L). p.G340D was found to be a common mutation in the Chinese MPS IVA patients, accounting for 16.7% of the total number of mutant alleles. The results show that the mutations in Chinese MPS IVA patients are also family specific but have a different mutation spectrum as compared to those of other populations.

  3. The I-Xe System in the IVA Iron Meteorite Steinbach

    NASA Astrophysics Data System (ADS)

    Pravdivtseva, O.; Meshik, A.; Hohenberg, C. M.

    2013-09-01

    Non-metallic phases from IVA Steinbach were separated and identified to be troilite, chromite, tridymite, and clino- and orthopyroxene. Xenon isotopic compositions are measured to identify possible iodine carrier phases suitable for the I-Xe dating.

  4. Role of elosulfase alfa in mucopolysaccharidosis IVA.

    PubMed

    Regier, Debra S; Tanpaiboon, Pranoot

    2016-01-01

    Mucopolysaccharidosis type IVA (MPS IVA or Morquio A) is an autosomal recessive lysosomal storage disease which results in a striking skeletal phenotype, but does not negatively impact the intellect of the patient. MPS IVA has a phenotypic continuum that ranges from a severe and rapidly progressing form to a slowly progressive form. The clinical diagnosis is often made in the preschool years based on abnormal bone findings on physical examination and dysplasia on radiographic imaging. Supportive care has been the mainstay in caring for patients. Orthopedic physicians often form the core of the care team due to the early and severe skeletal abnormalities; however, systemic disease is common and requires aggressive monitoring and management. Interdisciplinary care teams often consist of medical geneticists, cardiologists, pulmonary specialists, gastroenterologists, otolaryngologists, audiologists, and ophthalmologists. With the US Food and Drug Administration's approval of elosulfase alfa, patients >5 years of age now have access to this medication from the time of diagnosis. The clinical trial with once weekly intravenous dosing (2.0 mg/kg per week) showed improvement in the 6-minute walk test. The composite end point analysis to evaluate the combining changes from baseline in 6-minute walk test, 3-minute stair climb test, and respiratory function showed that at a dose of 2.0 mg/kg per week, subjects performed better when compared to placebo. This indication was clinically meaningful in the treatment group. The treatment was generally well tolerated, and the uncommon infusion reactions responded well to traditional enzyme replacement therapy infusion reaction management algorithms. Currently, clinical trials are underway to determine the efficacy and safety in MPS IVA patients <5 years of age.

  5. Role of elosulfase alfa in mucopolysaccharidosis IVA

    PubMed Central

    Regier, Debra S; Tanpaiboon, Pranoot

    2016-01-01

    Mucopolysaccharidosis type IVA (MPS IVA or Morquio A) is an autosomal recessive lysosomal storage disease which results in a striking skeletal phenotype, but does not negatively impact the intellect of the patient. MPS IVA has a phenotypic continuum that ranges from a severe and rapidly progressing form to a slowly progressive form. The clinical diagnosis is often made in the preschool years based on abnormal bone findings on physical examination and dysplasia on radiographic imaging. Supportive care has been the mainstay in caring for patients. Orthopedic physicians often form the core of the care team due to the early and severe skeletal abnormalities; however, systemic disease is common and requires aggressive monitoring and management. Interdisciplinary care teams often consist of medical geneticists, cardiologists, pulmonary specialists, gastroenterologists, otolaryngologists, audiologists, and ophthalmologists. With the US Food and Drug Administration’s approval of elosulfase alfa, patients >5 years of age now have access to this medication from the time of diagnosis. The clinical trial with once weekly intravenous dosing (2.0 mg/kg per week) showed improvement in the 6-minute walk test. The composite end point analysis to evaluate the combining changes from baseline in 6-minute walk test, 3-minute stair climb test, and respiratory function showed that at a dose of 2.0 mg/kg per week, subjects performed better when compared to placebo. This indication was clinically meaningful in the treatment group. The treatment was generally well tolerated, and the uncommon infusion reactions responded well to traditional enzyme replacement therapy infusion reaction management algorithms. Currently, clinical trials are underway to determine the efficacy and safety in MPS IVA patients <5 years of age. PMID:27366102

  6. Size of the Group IVA Iron Meteorite Parent Body

    NASA Astrophysics Data System (ADS)

    Moskovitz, N.; Walker, R.

    2011-10-01

    The group IVA fractionally crystallized iron meteorites display a diverse range of metallographic cooling rates, ranging from 100 - 6600 K/Myr [1]. These have been attributed to their formation in a metallic core, ˜150 km in radius that cooled to crystallization without any appreciable insulating mantle. Such an exposed core may have resulted from a hit-and-run collision [2] between two large (˜ 103 km) protoplanetary bodies. Here we build upon this formation scenario by incorporating several new constraints. These include (i) a recent U-Pb radiometric closure age of 4565.3 Mya (<2.5 Myr after CAIs) for the group IVA iron Muonionalusta [3], (ii) new measurements and modeling of highly siderophile element compositions for a suite of IVAs, and (iii) consideration of the thermal effects of heating by the decay of the short-lived radionuclide 60Fe.

  7. Preserving subject variability in group fMRI analysis: performance evaluation of GICA vs. IVA.

    PubMed

    Michael, Andrew M; Anderson, Mathew; Miller, Robyn L; Adalı, Tülay; Calhoun, Vince D

    2014-01-01

    Independent component analysis (ICA) is a widely applied technique to derive functionally connected brain networks from fMRI data. Group ICA (GICA) and Independent Vector Analysis (IVA) are extensions of ICA that enable users to perform group fMRI analyses; however a full comparison of the performance limits of GICA and IVA has not been investigated. Recent interest in resting state fMRI data with potentially higher degree of subject variability makes the evaluation of the above techniques important. In this paper we compare component estimation accuracies of GICA and an improved version of IVA using simulated fMRI datasets. We systematically change the degree of inter-subject spatial variability of components and evaluate estimation accuracy over all spatial maps (SMs) and time courses (TCs) of the decomposition. Our results indicate the following: (1) at low levels of SM variability or when just one SM is varied, both GICA and IVA perform well, (2) at higher levels of SM variability or when more than one SMs are varied, IVA continues to perform well but GICA yields SM estimates that are composites of other SMs with errors in TCs, (3) both GICA and IVA remove spatial correlations of overlapping SMs and introduce artificial correlations in their TCs, (4) if number of SMs is over estimated, IVA continues to perform well but GICA introduces artifacts in the varying and extra SMs with artificial correlations in the TCs of extra components, and (5) in the absence or presence of SMs unique to one subject, GICA produces errors in TCs and IVA estimates are accurate. In summary, our simulation experiments (both simplistic and realistic) and our holistic analyses approach indicate that IVA produces results that are closer to ground truth and thereby better preserves subject variability. The improved version of IVA is now packaged into the GIFT toolbox (http://mialab.mrn.org/software/gift).

  8. Preserving subject variability in group fMRI analysis: performance evaluation of GICA vs. IVA

    PubMed Central

    Michael, Andrew M.; Anderson, Mathew; Miller, Robyn L.; Adalı, Tülay; Calhoun, Vince D.

    2014-01-01

    Independent component analysis (ICA) is a widely applied technique to derive functionally connected brain networks from fMRI data. Group ICA (GICA) and Independent Vector Analysis (IVA) are extensions of ICA that enable users to perform group fMRI analyses; however a full comparison of the performance limits of GICA and IVA has not been investigated. Recent interest in resting state fMRI data with potentially higher degree of subject variability makes the evaluation of the above techniques important. In this paper we compare component estimation accuracies of GICA and an improved version of IVA using simulated fMRI datasets. We systematically change the degree of inter-subject spatial variability of components and evaluate estimation accuracy over all spatial maps (SMs) and time courses (TCs) of the decomposition. Our results indicate the following: (1) at low levels of SM variability or when just one SM is varied, both GICA and IVA perform well, (2) at higher levels of SM variability or when more than one SMs are varied, IVA continues to perform well but GICA yields SM estimates that are composites of other SMs with errors in TCs, (3) both GICA and IVA remove spatial correlations of overlapping SMs and introduce artificial correlations in their TCs, (4) if number of SMs is over estimated, IVA continues to perform well but GICA introduces artifacts in the varying and extra SMs with artificial correlations in the TCs of extra components, and (5) in the absence or presence of SMs unique to one subject, GICA produces errors in TCs and IVA estimates are accurate. In summary, our simulation experiments (both simplistic and realistic) and our holistic analyses approach indicate that IVA produces results that are closer to ground truth and thereby better preserves subject variability. The improved version of IVA is now packaged into the GIFT toolbox (http://mialab.mrn.org/software/gift). PMID:25018704

  9. Vasorelaxant effect of the aqueous extract of Ajuga iva in rat aorta.

    PubMed

    El-Hilaly, Jaouad; Lyoussi, Badiaâ; Wibo, Maurice; Morel, Nicole

    2004-07-01

    The aim of the present study was to investigate the ex vivo and in vitro vascular activity of the aqueous extract of Ajuga iva (L.) Schreber (Labiatae) in normotensive Wistar rats. Chronic oral administration of the extract of Ajuga iva did not significantly affect the systolic blood pressure. In aorta isolated from Ajuga iva-treated rats, the contractile response to noradrenaline was depressed compared to the responses obtained in aorta from untreated rats but the endothelium-dependent relaxation evoked by acetylcholine was not affected. In vitro, Ajuga iva extract inhibited the contraction evoked by noradrenaline. The addition of Ajuga iva extract during the plateau phase of noradrenaline-evoked contraction produced a relaxation that was sensitive to N-nitro-L-arginine. After pre-incubation of the artery in the presence of the plant extract, vasorelaxant effect was markedly less pronounced. The endothelium-dependent relaxation induced by acetylcholine was concentration-dependently blunted in the presence of Ajuga iva extract in the bathing solution. This study indicates that the aqueous extract of Ajuga iva possesses NO-mediated and NO-independent vasorelaxing properties in vitro while only the endothelium-independent effect was observed ex vivo.

  10. Therapies of mucopolysaccharidosis IVA (Morquio A syndrome).

    PubMed

    Tomatsu, Shunji; Alméciga-Díaz, Carlos J; Barbosa, Hector; Montaño, Adriana M; Barrera, Luis A; Shimada, Tsutomu; Yasuda, Eriko; Mackenzie, William G; Mason, Robert W; Suzuki, Yasuyuki; Orii, Kenji E; Orii, Tadao

    2013-10-01

    Morquio A syndrome (mucopolysaccharidosis type IVA, MPS IVA) is one of the lysosomal storage diseases and is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Deficiency of this enzyme leads to accumulation of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate (C6S). The majority of KS is produced by chondrocytes, and therefore, the undegraded substrates accumulate mainly in cells and extracelluar matrix (ECM) of cartilage. This has a direct impact on cartilage and bone development, leading to systemic skeletal dysplasia. In patients with Morquio A, cartilage cells are vacuolated, and this results in abnormal chondrogenesis and/or endochondral ossification. This article describes the advanced therapies of Morquio A, focused on enzyme replacement therapy (ERT) and gene therapy to deliver the drug to avascular bone lesions. ERT and gene therapies for other types of MPS are also discussed, which provide therapeutic efficacy to bone lesions. ERT, gene therapy and hematopietic stem therapy are clinically and/or experimentally conducted. However, there is no effective curative therapy for bone lesion to date. One of the limitations for Morquio A therapy is that targeting avascular cartilage tissues remains an unmet challenge. ERT or gene therapy with bone-targeting system will improve the bone pathology and skeletal manifestations more efficiently.

  11. Mature results of a pilot study of pelvic radiotherapy with concurrent continuous infusion intra-arterial 5-FU for stage IIIB-IVA squamous cell carcinoma of the cervix.

    PubMed

    Chaney, A W; Eifel, P J; Logsdon, M D; Morris, M; Wharton, J T

    1999-08-01

    To evaluate the long-term results of continuous infusion intra-arterial 5-fluorouracil (CI IA 5-FU) given with concurrent pelvic radiotherapy (RT) for FIGO stage IIIB-IVA carcinoma of the cervix. Between 1965 and 1974, 27 patients with extensive FIGO Stage IIIB (22 patients) or Stage IVA (5 patients) squamous cell carcinoma of the cervix were treated with CI IA 5-FU and RT. Twenty-one patients (78%) had bilateral pelvic wall involvement, 25 (93%) had massive tumors (> or =8 cm in diameter), 7 (27%) had involvement of the lower one-third of the vagina, and 15 (56%) presented with hydronephrosis. All patients underwent routine clinical staging, transperitoneal para-aortic lymph node dissection, and bilateral hypogastric artery catheter placement. 5-FU was continuously infused at a dose rate of 10 mg/kg/day on Days 1-15 of RT. The median dose of 5-FU was 376 mg/m2/day (range 270-692). All patients received concurrent pelvic RT to a median dose of 50 Gy at 2.0 Gy per fraction. Only 4 patients received intracavitary RT. The median follow-up of surviving patients was 190 months. The overall 5-year survival rate was 37%. For the 22 patients with FIGO Stage IIIB disease, the 5-year survival rate was 41%. The survival rate for 18 patients treated with only external beam radiation and chemotherapy for Stage IIIB disease was 33%. Four of 10 patients treated with only 50 Gy of external beam radiation and CI IA 5-FU were long-term survivors. Acute complications, including hematologic toxicity and skin reactions, were severe, with 1 death from neutropenic sepsis. Severe late complications were only observed in patients treated with > or =60 Gy of external beam radiation. While this series is small, the fact that 4 patients with massive Stage IIIB tumors survived after a total radiation dose of only 50 Gy suggests that RT with CI IA 5-FU deserves further study. Modifications in dose, technique, and route of administration should reduce toxicity, and the addition of intracavitary

  12. Structure-activity relationships of ω-Agatoxin IVA in lipid membranes.

    PubMed

    Ryu, Jae Ha; Jung, Hoi Jong; Konishi, Shiro; Kim, Ha Hyung; Park, Zee-Yong; Kim, Jae Il

    2017-01-01

    To analyze structural features of ω-Aga IVA, a gating modifier toxin from spider venom, we here investigated the NMR solution structure of ω-Aga IVA within DPC micelles. Under those conditions, the Cys-rich central region of ω-Aga IVA still retains the inhibitor Cys knot motif with three short antiparallel β-strands seen in water. However, (15)N HSQC spectra of ω-Aga IVA within micelles revealed that there are radical changes to the toxin's C-terminal tail and several loops upon binding to micelles. The C-terminal tail of ω-Aga IVA appears to assume a β-turn like conformation within micelles, though it is disordered in water. Whole-cell patch clamp studies with several ω-Aga IVA analogs indicate that both the hydrophobic C-terminal tail and an Arg patch in the core region of ω-Aga IVA are critical for Cav2.1 blockade. These results suggest that the membrane environment stabilizes the structure of the toxin, enabling it to act in a manner similar to other gating modifier toxins, though its mode of interaction with the membrane and the channel is unique.

  13. N-acetylglucosaminyltransferase IVa regulates metastatic potential of mouse hepatocarcinoma cells through glycosylation of CD147.

    PubMed

    Fan, Jianhui; Wang, Shujing; Yu, Shengjin; He, Jingna; Zheng, Weilong; Zhang, Jianing

    2012-08-01

    N-acetylglucosaminyltransferase (GnT)-IV a is a key enzyme that catalyzes the formation of the GlcNAC β1-4 branch on the core structure of complex N-Glycans, which is the common substrate for other N-acetylglucosaminyltransferases, such as GnT-III and GnT-V. Our recent study indicates that the expression of GnT-IVa in Hca-F cells was much higher than that in Hepa1-6 cells, these two mouse hepatocarcinoma cell lines have high and no metastatic potential in lymph nodes respectively. To investigate the effects of GnT-IVa on the metastasis of hepatocarcinoma, exogenous GnT-IVa was introduced into Hepa1-6 cells, and on the other hand, the expression of GnT-IVa was down-regulated in Hca-F cells. The engineered overexpression of GnT-IVa in Hepa1-6 cells increased the antennary branches of complex N-glycans and reduced bisecting branches in vitro and in vivo, which leads to the increase in migration and metastatic capability of hepatocarcinoma cells. Conversely, down-regulated expression of GnT-IVa in Hca-F cells showed reduced tetra-antennary branches of N-Glycans, and significantly decreased the migration and metastatic capability. Furthermore, we found that the regulated GnT-IVa converts the heterogeneous N-glycosylated forms of CD147 in Hepa1-6 and Hca-F cells, and significantly changed the antennary oligosaccharide structures on CD147. These results suggest that GnT-IVa could be acting as a key role in migration and metastasis of mouse hepatocarcinoma cells through altering the glycosylation of CD147. These findings should be valuable in delineating the important function of GnT-IVa during the process of hepatocarcinoma growth and metastasis.

  14. Bisphosphonate Treatment in a Patient Affected by MPS IVA with Osteoporotic Phenotype.

    PubMed

    Tummolo, Albina; Gabrielli, Orazio; Gaeta, Alberto; Masciopinto, Maristella; Zampini, Lucia; Pavone, Luigi Michele; Di Natale, Paola; Papadia, Francesco

    2013-01-01

    Morquio A syndrome (Mucopolysaccharidosis type IVA) (MPS IVA) is a rare inherited metabolic disorder characterized by the defective degradation of keratan sulfate and chondroitin-6-sulfate. Classically, MPS IVA patients present with severe multisystemic involvement and have a short life expectancy. Attenuated forms with clinical features limited to minor skeletal abnormalities and short stature have also been described, sometimes associated to an early-onset osteoporotic phenotype. No treatment with allogenic bone marrow transplantation or gene therapy is currently available for Morquio A syndrome, and enzyme replacement therapy is under evaluation. We report a case of MPS IVA, who manifested tardily attenuated phenotype and significant bone mass reduction, which was treated with a bisphosphonate (BPN), resulting in an improvement of X-ray skeletal aspects and functional bone performance. We suggest that the use of bisphosphonates may be an interesting supportive therapeutic option for Morquio A patients with osteoporotic phenotype, but further studies involving more patients are necessary to confirm our findings.

  15. Pan PPAR agonist IVA337 is effective in prevention and treatment of experimental skin fibrosis

    PubMed Central

    Ruzehaji, Nadira; Frantz, Camelia; Ponsoye, Matthieu; Avouac, Jerome; Pezet, Sonia; Guilbert, Thomas; Luccarini, Jean-Michel; Broqua, Pierre; Junien, Jean-Louis; Allanore, Yannick

    2016-01-01

    Background The pathogenesis of systemic sclerosis (SSc) involves a distinctive triad of autoimmune, vascular and inflammatory alterations resulting in fibrosis. Evidence suggests that peroxisome proliferator-activated receptors (PPARs) play an important role in SSc-related fibrosis and their agonists may become effective therapeutic targets. Objective To determine the expression of PPARs in human fibrotic skin and investigate the effects of IVA337, a pan PPAR agonist, in in vitro and in vivo models of fibrosis. Methods The antifibrotic effects of IVA337 were studied using a bleomycin-induced mouse model of dermal fibrosis. The in vivo effect of IVA337 on wound closure and inflammation were studied using an excisional model of wound healing. Results Low levels of PPARα and PPARγ were detected in the skin of patients with SSc compared with controls. In mice, IVA337 was associated with decreased extracellular matrix (ECM) deposition and reduced expression of phosphorylated SMAD2/3—intracellular effector of transforming growth factor (TGF)-β1. Although the antifibrotic effect of pan PPAR was similar to that of PPARγ agonist alone, a significant downregulation of several markers of inflammation was associated with IVA337. Despite its anti-inflammatory and antifibrotic properties, IVA337 did not interfere with wound closure. In vitro effects of IVA337 included attenuation of transcription of ECM genes and alteration of canonical and non-canonical TGF-β signalling pathways. Conclusions These findings indicate that simultaneous activation of all three PPAR isoforms exerts a dampening effect on inflammation and fibrosis, making IVA337 a potentially effective therapeutic candidate in the treatment of fibrotic diseases including SSc. PMID:26961294

  16. Chondroitin 6-Sulfate as a Novel Biomarker for Mucopolysaccharidosis IVA and VII.

    PubMed

    Shimada, Tsutomu; Tomatsu, Shunji; Yasuda, Eriko; Mason, Robert W; Mackenzie, William G; Shibata, Yuniko; Kubaski, Francyne; Giugliani, Roberto; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Kenji; Orii, Tadao

    2014-01-01

    Chondroitin 6-sulfate (C6S), a glycosaminoglycan (GAG), is distributed mainly in the growth plates, aorta, and cornea; however, the physiological function of C6S is not fully understood. One of the limitations is that no rapid, accurate quantitative method to measure C6S has been established. Mucopolysaccharidosis IVA and VII (MPS IVA and VII) are caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase and β-D-glucuronidase, respectively, resulting in accumulation of C6S and other GAG(s). While levels of keratan sulfate (KS), heparan sulfate, and dermatan sulfate in samples from MPS patients are well described, this is the first report of quantitative analysis of C6S levels in samples from MPS IVA and VII patients.We developed a method to digest polymeric C6S and measure resultant disaccharides using liquid chromatography-tandem mass spectrometry (LC-MS/MS). C6S levels were measured in the blood from control subjects and patients with MPS IVA and VII aged from 0 to 58 years of age. We also assayed KS levels in the same samples for comparison with C6S.Levels of C6S in the blood decreased with age and were significantly elevated in patients with MPS IVA and VII, compared with age-matched controls. Levels of KS in patients with MPS IVA were also higher than those in age-matched controls, although differences were less pronounced than with C6S. Combining KS and C6S data, discriminated patients with MPS IVA from age-matched control subjects were better than either C6S or KS levels alone.In conclusion, this first report showing that blood levels of C6S are quantitatively evaluated in patients with MPS IVA and VII indicates that C6S could be a useful biomarker for these metabolic disorders.

  17. Oxidative stress and inflammation in mucopolysaccharidosis type IVA patients treated with enzyme replacement therapy.

    PubMed

    Donida, Bruna; Marchetti, Desirèe P; Biancini, Giovana B; Deon, Marion; Manini, Paula R; da Rosa, Helen T; Moura, Dinara J; Saffi, Jenifer; Bender, Fernanda; Burin, Maira G; Coitinho, Adriana S; Giugliani, Roberto; Vargas, Carmen Regla

    2015-05-01

    Mucopolysaccharidosis type IVA (MPS IVA) is an inborn error of glycosaminoglycan (GAG) catabolism due to the deficient activity of N-acetylgalactosamine-6-sulfate sulfatase that leads to accumulation of the keratan sulfate and chondroitin 6-sulfate in body fluids and in lysosomes. The pathophysiology of this lysosomal storage disorder is not completely understood. The aim of this study was to investigate oxidative stress parameters, pro-inflammatory cytokine and GAG levels in MPS IVA patients. We analyzed urine and blood samples from patients under ERT (n=17) and healthy age-matched controls (n=10-15). Patients presented a reduction of antioxidant defense levels, assessed by a decrease in glutathione content and by an increase in superoxide dismutase activity in erythrocytes. Concerning lipid and protein damage, it was verified increased urine isoprostanes and di-tyrosine levels and decreased plasma sulfhydryl groups in MPS IVA patients compared to controls. MPS IVA patients showed higher DNA damage than control group and this damage had an oxidative origin in both pyrimidine and purine bases. Interleukin 6 was increased in patients and presented an inverse correlation with GSH levels, showing a possible link between inflammation and oxidative stress in MPS IVA disease. The data presented suggest that pro-inflammatory and pro-oxidant states occur in MPS IVA patients even under ERT. Taking these results into account, supplementation of antioxidants in combination with ERT can be a tentative therapeutic approach with the purpose of improving the patient's quality of life. To the best of our knowledge, this is the first study relating MPS IVA patients with oxidative stress. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Vessel shape alterations of the vertebrobasilar arteries in Mucopolysaccharidosis type IVa (Morquio A) patients.

    PubMed

    Tanyildizi, Yasemin; Gökce, Seyfullah; Marini, Federico; Mayer, Anna K; Kirschner, Stefanie; Hennermann, Julia B; Brockmann, Marc A

    2017-08-01

    Main symptom of mucopolysaccharidosis type IVa (MPS IVa) is progressive systemic skeletal dysplasia. This is routinely monitored by cerebral and spinal MRI. The vascular system is generally not in the primary focus of interest. In our population of MPS IVa patients we observed vessel shape alterations of the vertebrobasilar arteries, which has not been described before. MRI-datasets of 26 patients with MPS IVa acquired between 2008 and 2015 were eligible for retrospective analysis of the vertebrobasilar arteries. The vessel length and angle of the basilar artery (BA) and both vertebral arteries (VA) were analyzed. A deflection angle between 90° and 130° in the vessel course was defined as tortuosity, less than 90° as kinking. The results were compared to a matched control group of 23 patients not suffering from MPS. The deflection angle [°] of the VA and BA was significantly decreased in the majority (85%) of MPS IVa patients compared to the control group: BA 132±24 vs. 177±6, BA/VA transition 113±21 vs. 152±13, right VA 108±23 vs. 156±13, left VA 110± 22 vs. 157±14 (all p<0.005). Likewise, vessels of MPS IVa patients were significantly longer compared to the control group: BA 27±4 vs. 21±2, right VA 20±6 vs. 10±1, left VA 18±5 vs. 11±2 (all p<0.005). MPS IVa is associated with significantly increased tortuosity of vertebrobasilar arteries. Therefore the vascular system of MPS IVa patients should be monitored on routinely basis, as vessel shape alterations had been associated with dissections, leading to a higher risk of cerebrovascular events. Copyright © 2017. Published by Elsevier B.V.

  19. Pan PPAR agonist IVA337 is effective in prevention and treatment of experimental skin fibrosis.

    PubMed

    Ruzehaji, Nadira; Frantz, Camelia; Ponsoye, Matthieu; Avouac, Jerome; Pezet, Sonia; Guilbert, Thomas; Luccarini, Jean-Michel; Broqua, Pierre; Junien, Jean-Louis; Allanore, Yannick

    2016-12-01

    The pathogenesis of systemic sclerosis (SSc) involves a distinctive triad of autoimmune, vascular and inflammatory alterations resulting in fibrosis. Evidence suggests that peroxisome proliferator-activated receptors (PPARs) play an important role in SSc-related fibrosis and their agonists may become effective therapeutic targets. To determine the expression of PPARs in human fibrotic skin and investigate the effects of IVA337, a pan PPAR agonist, in in vitro and in vivo models of fibrosis. The antifibrotic effects of IVA337 were studied using a bleomycin-induced mouse model of dermal fibrosis. The in vivo effect of IVA337 on wound closure and inflammation were studied using an excisional model of wound healing. Low levels of PPARα and PPARγ were detected in the skin of patients with SSc compared with controls. In mice, IVA337 was associated with decreased extracellular matrix (ECM) deposition and reduced expression of phosphorylated SMAD2/3-intracellular effector of transforming growth factor (TGF)-β1. Although the antifibrotic effect of pan PPAR was similar to that of PPARγ agonist alone, a significant downregulation of several markers of inflammation was associated with IVA337. Despite its anti-inflammatory and antifibrotic properties, IVA337 did not interfere with wound closure. In vitro effects of IVA337 included attenuation of transcription of ECM genes and alteration of canonical and non-canonical TGF-β signalling pathways. These findings indicate that simultaneous activation of all three PPAR isoforms exerts a dampening effect on inflammation and fibrosis, making IVA337 a potentially effective therapeutic candidate in the treatment of fibrotic diseases including SSc. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  20. 129I interlaboratory comparison: phase I and phase II results

    SciTech Connect

    Roberts, M.I.; Caffee, M.W.; Proctor, I.D.

    1997-07-01

    An interlaboratory comparison exercise for 129I was organized and conducted. A total of nine laboratories participated in the exercise to either a full or limited extent. In Phase I of the comparison, a suite of 11 samples were measured. The suite of samples contained both synthetic `standard type` materials (i.e., AgI) and environmental materials. The isotopic 129I/127I ratios of the samples varied from 10`-8 to 10`-14. In this phase, each laboratory was responsible for its own chemical preparation of the environmental samples. The 129I AMS measurements obtained at different laboratories for prepared AgI were in good agreement. However, large discrepancies were seen in 129I AMS measurements of environmental samples. Because of the large discrepancies seen in the Phase I intercomparison, a subsequent study was conducted. In Phase II of the comparison, AgI was prepared from two environmental samples (IAEA 375 soil and maples leaves) by three separate laboratories. Each laboratory used its own chemical preparation method with each of the methods being distinctly different. The resulting six samples (two sets of three) were then redistributed to the participating 129I AMS facilities and 129I/127I ratios measured. Results and discussion of both the Phase I and Phase II interlaboratory comparison are presented.

  1. Phase II Trial of Hyperfractionated Intensity-Modulated Radiation Therapy and Concurrent Weekly Cisplatin for Stage III and IVa Head-and-Neck Cancer

    SciTech Connect

    Maguire, Patrick D.; Papagikos, Michael; Hamann, Sue; Neal, Charles; Meyerson, Martin; Hayes, Neil; Ungaro, Peter; Kotz, Kenneth; Couch, Marion; Pollock, Hoke; Tepper, Joel

    2011-03-15

    Purpose: To investigate a novel chemoradiation regimen designed to maximize locoregional control (LRC) and minimize toxicity for patients with advanced head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Patients received hyperfractionated intensity modulated radiation therapy (HIMRT) in 1.25-Gy fractions b.i.d. to 70 Gy to high-risk planning target volume (PTV). Intermediate and low-risk PTVs received 60 Gy and 50 Gy, at 1.07, and 0.89 Gy per fraction, respectively. Concurrent cisplatin 33 mg/m{sup 2}/week was started Week 1. Patients completed the Quality of Life Radiation Therapy Instrument pretreatment (PRE), at end of treatment (EOT), and at 1, 3, 6, 9, and 12 months. Overall survival (OS), progression-free (PFS), LRC, and toxicities were assessed. Results: Of 39 patients, 30 (77%) were alive without disease at median follow-up of 37.5 months. Actuarial 3-year OS, PFS, and LRC were 80%, 82%, and 87%, respectively. No failures occurred in the electively irradiated neck and there were no isolated neck failures. Head and neck QOL was significantly worse in 18 of 35 patients (51%): mean 7.8 PRE vs. 3.9 EOT. By month 1, H and N QOL returned near baseline (mean 6.2, SD = 1.7). The most common acute Grade 3+ toxicities were mucositis (38%), fatigue (28%), dysphagia (28%), and leukopenia (26%). Conclusions: Hyperfractionated IMRT with low-dose weekly cisplatin resulted in good LRC with acceptable toxicity and QOL. Lack of elective nodal failures despite very low dose per fraction has led to an attempt to further minimize toxicity by reducing elective nodal doses in our subsequent protocol.

  2. Antithrombotic effect of chikusetsusaponin IVa isolated from Ilex paraguariensis (Maté).

    PubMed

    Dahmer, Tabitha; Berger, Markus; Barlette, Adriana Gregory; Reck, José; Segalin, Jéferson; Verza, Simone; Ortega, George González; Gnoatto, Simone Cristina Baggio; Guimarães, Jorge Almeida; Verli, Hugo; Gosmann, Grace

    2012-12-01

    The triterpene chikusetsusaponin IVa was isolated from the fruit of Ilex paraguariensis. Using biochemical and pharmacological methods, we demonstrated that chikusetsusaponin IVa (1) prolongs the recalcification time, prothrombin time, activated partial thromboplastin time, and thrombin time of normal human plasma in a dose-dependent manner, (2) inhibits the amidolytic activity of thrombin and factor Xa upon synthetic substrates S2238 and S2222, (3) inhibits thrombin-induced fibrinogen clotting (50% inhibition concentration, 199.4 ± 9.1 μM), and (4) inhibits thrombin- and collagen-induced platelet aggregation. The results also indicate that chikusetsusaponin IVa preferentially inhibits thrombin in a competitive manner (K(i)=219.6 μM). Furthermore, when administered intravenously to rats, chikusetsusaponin IVa inhibited thrombus formation in a stasis model of venous thrombosis, although it did not induce a significant bleeding effect. Chikusetsusaponin IVa also prolonged the ex vivo activated partial thromboplastin time. Altogether, these data suggest that chikusetsusaponin IVa exerts antithrombotic effects, including minor hemorrhagic events. This appears to be important for the development of new therapeutic agents.

  3. Robonaut 2 on the International Space Station: Status Update and Preparations for IVA Mobility

    NASA Technical Reports Server (NTRS)

    Ahlstrom, Thomas D.; Diftler, Myron E.; Berka, Reginald B.; Badger, Julia M.; Yayathi, Sandeep; Curtis, Andrew W.; Joyce, Charles A.

    2013-01-01

    Robotics engineers, ground controllers and International Space Station (ISS) crew have been running successful experiments using Robonaut 2 (R2) on-board the ISS for more than a year. This humanoid upper body robot continues to expand its list of achievements and its capabilities to safely demonstrate maintenance and servicing tasks while working alongside human crewmembers. The next phase of the ISS R2 project will transition from a stationary Intra Vehicular Activity (IVA) upper body using a power/data umbilical, to an IVA mobile system with legs for repositioning, a battery backpack power supply, and wireless communications. These upgrades will enable the R2 team to evaluate hardware performance and to develop additional control algorithms and control verification techniques with R2 inside the ISS in preparation for the Extra Vehicular Activity (EVA) phase of R2 operations. As R2 becomes more capable in assisting with maintenance tasks, with minimal supervision, including repositioning itself to different work sites, the ISS crew will be burdened with fewer maintenance chores, leaving them more time to conduct other activities. R2's developers at the Johnson Space Center (JSC) are preparing the R2 IVA mobility hardware and software upgrades for delivery to the ISS in late 2013. This paper summarizes R2 ISS achievements to date, briefly describes the R2 IVA mobility upgrades, and discusses the R2 IVA mobility objectives and plans.

  4. Laparoscopic Radiofrequency Fibroid Ablation: Phase II and Phase III Results

    PubMed Central

    Pemueller, Rodolfo Robles; Garza Leal, José Gerardo; Abbott, Karen R.; Falls, Janice L.; Macer, James

    2014-01-01

    Background and Objectives: To review phase II and phase III treatments of symptomatic uterine fibroids (myomas) using laparoscopic radiofrequency volumetric thermal ablation (RFVTA). Methods: We performed a retrospective, multicenter clinical analysis of 206 consecutive cases of ultrasound-guided laparoscopic RFVTA of symptomatic myomas conducted on an outpatient basis under two phase II studies at 2 sites (n = 69) and one phase III study at 11 sites (n = 137). Descriptive and exploratory, general trend, and matched-pair analyses were applied. Results: From baseline to 12 months in the phase II study, the mean transformed symptom severity scores improved from 53.9 to 8.8 (P < .001) (n = 57), health-related quality-of-life scores improved from 48.5 to 92.0 (P < .001) (n = 57), and mean uterine volume decreased from 204.4 cm3 to 151.4 cm3 (P = .008) (n = 58). Patients missed a median of 4 days of work (range, 2–10 days). The rate of possible device-related adverse events was 1.4% (1 of 69). In the phase III study, approximately 98% of patients were assessed at 12 months, and their transformed symptom severity scores, health-related quality-of-life scores, mean decrease in uterine volume, and mean menstrual bleeding reduction were also significant. Patients in phase III missed a median of 5 days of work (range, 1–29 days). The rate of periprocedural device-related adverse events was 3.5% (5 of 137). Despite the enrollment requirement for patients in both phases to have completed childbearing, 4 pregnancies occurred within the first year after treatment. Conclusions: RFVTA does not require any uterine incisions and provides a uterine-sparing procedure with rapid recovery, significant reduction in uterine size, significant reduction or elimination of myoma symptoms, and significant improvement in quality of life. PMID:24960480

  5. Molecular analysis of mucopolysaccharidosis IVA: Common mutations and racial difference

    SciTech Connect

    Tomatsu, S.; Hori, T.; Nakashima, Y.

    1994-09-01

    Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by a deficiency in N-acetylgalactosamine -6-sulfate sulfatase (GALNS). Studies on the molecular basis of MPS IVA have been facilitated following cloning of the full-length cDNA and genomic DNA. In this study we detected mutations from 20 Caucasian and 19 Japanese MPS IVA patients using SSCP system and compared mutations of Caucasian origin with those of Japanese origin. The results showed the presence of 16 various mutations (3 small, deletions, 2 nonsense and 11 missense mutations) for Caucasian patients and 15 (1 deletion, 1 large alteration and 13 missense mutations) for Japanese. Moreover, two common mutations existed; one is double gene deletion characteristic for Japanese (6 alleles; 15%) and the other is a point mutation (1113F A{yields}T transition) characteristic for Caucasian (9 alleles; 22.5%). And the clear genotype/phenotype relationship among 1342delCA, IVS1(-2), P151S, Q148X, R386C, I113F, Q473X, W220G, P151L, A291T, R90W, and P77R, for a severe type, G96B N204K and V138A for a milder type, was observed. Only R386 mutation was seen in both of the populations. Further, the precise DNA analysis for double gene deletion of a common double gene deletion has been performed by defining the breakpoints and the results showed that one deletion was caused by homologous recombination due to Alu repetitive sequences and the other was due to nonhomologous recombination of short direct repeat. Haplotype analysis for six alleles with double deletion were different, indicating the different origin of this mutation or the frequent recombination events before a mutational event. Thus the mutations in GALNS gene are very heterogeneous and the racial difference is characteristic.

  6. Molecular genetic assay of mucopolysaccharidosis IVA in South China.

    PubMed

    He, Dengmin; Huang, Yonglan; Ou, Zhiying; Sheng, Huiying; Li, Sheyong; Zhao, Xiaoyuan; Li, Ru; Zheng, Jipeng; Liu, Li

    2013-12-10

    Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Molecular mutational analysis was performed by PCR product sequencing for fourteen exons and exon-intron boundaries of GALNS gene in 21 patients from 19 unrelated families with severe MPS IVA in South China. We identified fifteen different mutations, including 10 reported mutations (p.P125L, p.G290S, p.M318R, p.G340D, p.L366P, p.R386C, p.A392V, c.1243-1G>C, p.L440RfsX54 and p.X523E) and five novel mutations (p.N177S, p.G290R, p.F306S, p.W403_T404delinsCS, p.W520X). All five novel mutations were inherited from parents of the patients and not found in 100 normal control alleles. Three mutations, p.M318R, p.L366P and p.R386C were common, accounting for 36.8% of mutant alleles investigated. One patient homozygous of p.A392V and the other two unrelated patients homozygous of p.L366P presented classical disease course. The results show that the GALNS gene has a different mutational spectrum in South China as compared to other regions. The p.A392V and p.L366P mutations were associated with severe phenotype of MPS IVA. © 2013 Elsevier B.V. All rights reserved.

  7. First results from GERDA Phase II

    NASA Astrophysics Data System (ADS)

    Agostini, M.; Allardt, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D’Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gooch, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Palioselitis, D.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Selivanenko, O.; Shevchik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.

    2017-09-01

    Gerda is designed for a background-free search of 76Ge neutrinoless double-β decay, using bare Ge detectors in liquid Ar. The experiment was upgraded after the successful completion of Phase I to double the target mass and further reduce the background. Newly-designed Ge detectors were installed along with LAr scintillation sensors. Phase II of data-taking started in Dec 2015 with approximately 36 kg of Ge detectors and is currently ongoing. The first results based on 10.8 kg· yr of exposure are presented. The background goal of 10‑3 cts/(keV· kg· yr) is achieved and a search for neutrinoless double-β decay is performed by combining Phase I and II data. No signal is found and a new limit is set at T1/20ν > 5.3 \\cdot {1025} yr (90% C.L.).

  8. The thermal evolution of IVA iron meteorites: Evidence from metallographic cooling rates.

    NASA Astrophysics Data System (ADS)

    Rasmussen, Kaare L.; Ulff-Møller, Finn; Haack, Henning

    1995-07-01

    Metallographic cooling rates of group IVA iron meteorites have been recalculated based on the most recent Ni diffusion coefficients and phase diagram. The cooling rates are revised upwards by a factor of ca. 15 relative to previous estimates. A large range in cooling rate is found in the low-Ni part of group IVA (Ni < 8.4 wt%), while the high-Ni part shows approximately constant cooling rates. Undercooling is observed only in the high-Ni IVA members. Some of the taenite lamellae in the high-Ni IVA irons, which were apparently affected by moderate undercooling, can, alternatively, be interpreted to have experienced a nonlinear cooling history. The variation in cooling rate of the entire group IVA spans two orders of magnitude (19-3400 K/My). This span is still so large that it constitutes severe problems for both a core origin model and a raisin-bread model but seemingly it does not contradict a model where the parent body is broken up and reassembled after core crystallization but prior to Widmanstätten pattern formation.

  9. Architecture of the type IVa pilus machine.

    PubMed

    Chang, Yi-Wei; Rettberg, Lee A; Treuner-Lange, Anke; Iwasa, Janet; Søgaard-Andersen, Lotte; Jensen, Grant J

    2016-03-11

    Type IVa pili are filamentous cell surface structures observed in many bacteria. They pull cells forward by extending, adhering to surfaces, and then retracting. We used cryo-electron tomography of intact Myxococcus xanthus cells to visualize type IVa pili and the protein machine that assembles and retracts them (the type IVa pilus machine, or T4PM) in situ, in both the piliated and nonpiliated states, at a resolution of 3 to 4 nanometers. We found that T4PM comprises an outer membrane pore, four interconnected ring structures in the periplasm and cytoplasm, a cytoplasmic disc and dome, and a periplasmic stem. By systematically imaging mutants lacking defined T4PM proteins or with individual proteins fused to tags, we mapped the locations of all 10 T4PM core components and the minor pilins, thereby providing insights into pilus assembly, structure, and function. Copyright © 2016, American Association for the Advancement of Science.

  10. Radiation therapy for stage IVA cervical cancer.

    PubMed

    Murakami, Naoya; Kasamatsu, Takahiro; Morota, Madoka; Sumi, Minako; Inaba, Koji; Ito, Yoshinori; Itami, Jun

    2013-11-01

    To evaluate the outcome and discover predictive factors for patients with stage IVA cervical cancer treated with definitive radiation therapy. We retrospectively reviewed 34 patients with stage IVA cervical cancer who received definitive radiation therapy between 1992 and 2009. On univariate analysis, statistically significant prognostic factors for improved local control rate (LCR) were absence of pyometra (p=0.037) and equivalent dose in 2 Gy fractions (EQD2) at point A greater than 60 Gy (p=0.023). Prognostic factors for improved progression-free survival (PFS) were absence of pelvic lymph node metastasis at initial presentation (p=0.014), and EQD2 at point A greater than 60 Gy (p=0.023). Patients with stage IVA disease had poor median survival. However adequate radiation dose to point A produced favorable LCR and PFS, therefore efforts should be made to increase the point A dose.

  11. Phase 2 microwave concrete decontamination results

    SciTech Connect

    White, T.L.; Foster, D. Jr.; Wilson, C.T.; Schaich, C.R.

    1995-04-01

    The authors report on the results of the second phase of a four-phase program at Oak Ridge National Laboratory to develop a system to decontaminate concrete using microwave energy. The microwave energy is directed at the concrete surface through the use of an optimized wave guide antenna, or applicator, and this energy rapidly heats the free water present in the interstitial spaces of the concrete matrix. The resulting steam pressure causes the surface to burst in much the same way popcorn pops in a home microwave oven. Each steam explosion removes several square centimeters of concrete surface that are collected by a highly integrated wave guide and vacuum system. The authors call this process the microwave concrete decontamination, or MCD, process. In the first phase of the program the principle of microwaves concrete removal concrete surfaces was demonstrated. In these experiments, concrete slabs were placed on a translator and moved beneath a stationary microwave system. The second phase demonstrated the ability to mobilize the technology to remove the surfaces from concrete floors. Area and volume concrete removal rates of 10.4 cm{sup 2}/s and 4.9 cm{sup 3}/S, respectively, at 18 GHz were demonstrated. These rates are more than double those obtained in Phase 1 of the program. Deeper contamination can be removed by using a longer residence time under the applicator to create multiple explosions in the same area or by taking multiple passes over previously removed areas. Both techniques have been successfully demonstrated. Small test sections of painted and oil-soaked concrete have also been removed in a single pass. Concrete with embedded metal anchors on the surface has also been removed, although with some increased variability of removal depth. Microwave leakage should not pose any operational hazard to personnel, since the observed leakage was much less than the regulatory standard.

  12. CAPTURING SUBJECT VARIABILITY IN FMRI DATA : A GRAPH-THEORETICAL ANALYSIS OF GICA VS. IVA

    PubMed Central

    Laney, Jonathan; Westlake, Kelly; Ma, Sai; Woytowicz, Elizabeth; Calhoun, Vince D.; Adalı, Tülay

    2016-01-01

    Background Recent studies using simulated functional magnetic resonance imaging (fMRI) data show that independent vector analysis (IVA) is a superior solution for capturing spatial subject variability when compared with the widely used group independent component analysis (GICA). Retaining such variability is of fundamental importance for identifying spatially localized group differences in intrinsic brain networks. New Methods Few studies on capturing subject variability and order selection have evaluated real fMRI data. Comparison of multivariate components generated by multiple algorithms is not straightforward. The main difficulties are finding concise methods to extract meaningful features and comparing multiple components despite lack of a ground truth. In this paper, we present a graph-theoretic approach to effectively compare the ability of multiple multivariate algorithms to capture subject variability for real fMRI data for effective group comparisons. Results Discriminating trends in features calculated from IVA- and GICA-generated components show that IVA better preserves the qualities of centrality and small worldness in fMRI data. IVA also produced components with more activated voxels leading to larger area under the curve (AUC) values. Comparison with Existing Method IVA is compared with widely used GICA for the purpose of group discrimination in terms of graph-theoretic features. In addition, masks are applied for motor related components generated by both algorithms. Conclusions Results show IVA better captures subject variability producing more activated voxels and generating components with less mutual information in the spatial domain than Group ICA. IVA-generated components result in smaller p-values and clearer trends in graph-theoretic features. PMID:25797843

  13. Clinical, radiologic, and genetic features of Korean patients with Mucopolysaccharidosis IVA.

    PubMed

    Lee, Na Hee; Cho, Sung Yoon; Maeng, Se Hyun; Jeon, Tae Yeon; Sohn, Young Bae; Kim, Su Jin; Park, Hyung-Doo; Jin, Dong Kyu

    2012-11-01

    Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is rare lysosomal storage disorder caused by N-acetylgalactosamine-6-sulfatase (GALNS) deficiency. Only a few MPS IVA cases have been reported in the Korean literature; there is a paucity of research about clinical or radiologic findings for this disorder. Therefore, we studied clinical findings, radiological features, and genetic data of Korean MPS IVA patients for determining factors that may allow early diagnosis and that may thus improve the patients' quality of life. MPS IVA was confirmed via assay for enzymatic activity of leukocytes in 10 patients. The GALNS gene was analyzed. Patients' charts were retrospectively reviewed for obtaining clinical features and evaluated for radiological skeletal surveys, echocardiography, pulmonary function test, and ophthalmologic test results. Nine patients had severe clinical phenotype, and 1 had an intermediate phenotype, on the basis of clinical phenotype criteria. Radiologic findings indicated skeletal abnormalities in all patients, especially in the hips and extremities. Eight patients had an odontoid hypoplasia, and 1 showed mild atlantoaxial subluxation and cord myelopathy. Genetic analysis indicated 10 different GALNS mutations. Two mutations, c.451C>A and c.1000C>T, account for 37.5% (6/16) and 25% (4/16) of all mutations in this samples, respectively. An understanding of the clinical and radiological features involved in MPS IVA may allow early diagnosis of MPS IVA. Adequate evaluations and therapy in the early stages may improve the quality of life of patients suffering from skeletal abnormalities and may reduce life-threatening effects of atlantoaxial subluxation.

  14. High expression of N-acetylglucosaminyltransferase IVa promotes invasion of choriocarcinoma

    PubMed Central

    Niimi, K; Yamamoto, E; Fujiwara, S; Shinjo, K; Kotani, T; Umezu, T; Kajiyama, H; Shibata, K; Ino, K; Kikkawa, F

    2012-01-01

    Background: Gestational trophoblastic diseases (GTDs) are related to trophoblasts, and human chorionic gonadotropin (hCG) is secreted by GTDs as well as normal placentas. However, the asparagine-linked sugar chains on hCG contain abnormal biantennary structures in invasive mole and choriocarcinoma, but not normal pregnancy or hydatidiform mole. N-acetylglucosaminyltransferase-IV (GnT-IV) catalyses β1,4-N-acetylglucosamine branching on asparagine-linked oligosaccharides, which are consistent with the abnormal sugar chain structures on hCG. Methods: We investigated GnT-IVa expression in GTDs and placentas by immunohistochemistry, western blot, and RT–PCR. We assessed the effects of GnT-IVa knockdown in choriocarcinoma cells in vitro and in vivo. Results: The GnT-IVa was highly expressed in trophoblasts of invasive mole and choriocarcinoma, and moderately in extravillous trophoblasts during the first trimester, but not in hydatidiform mole or other normal trophoblasts. The GnT-IVa knockdown in choriocarcinoma cells significantly reduced migration and invasive capacities, and suppressed cellular adhesion to extracellular matrix proteins. The extent of β1,4-N-acetylglucosamine branching on β1 integrin was greatly reduced by GnT-IVa knockdown, although the expression of β1 integrin was not changed. In vivo studies further demonstrated that GnT-IVa knockdown suppressed tumour engraftment and growth. Conclusion: These findings suggest that GnT-IVa is involved in regulating invasion of choriocarcinoma through modifications of the oligosaccharide chains of β1 integrin. PMID:23169300

  15. IVA. Improving Vocational Administration. Final Report.

    ERIC Educational Resources Information Center

    EPD Consortium D, Richardson, TX.

    The Texas Improving Vocational Administration (IVA) project was conceived to improve preservice and inservice programs for vocational education administrators. Primary objectives were to (1) develop a method, including a survey, to determine existing inservice and preservice administrative training program competencies; (2) determine, using the…

  16. Atypical presentation of mucopolysaccharidosis type IVA.

    PubMed

    Rush, Eric T

    2016-09-01

    A 14 year old patient with short stature, type I diabetes, and cataracts was referred for evaluation of avascular necrosis of the femoral head. Radiography was suggestive of spondyloepiphyseal dysplasia with decreased bone mineral density for age. Targeted molecular and biochemical testing were normal in this patient. Whole exome sequencing was performed and showed compound heterozygosity for previously reported pathogenic GALNS variants which were diagnostic of mucopolysaccharidosis, type IVA (Morquio A). While this case describes neither a novel condition nor a new mutation, it does illustrate three important points in the diagnosis of patients with atypical forms of MPS IVA. First, that in many instances urine glycosaminoglycan analysis is not sufficient to rule out MPS IVA as a potential diagnosis. Patients in whom biochemical screening is advised should have measurement of leukocyte enzymatic activity. Second, that in patients with radiographic evidence of spondyloepiphyseal dysplasia with additional features or with normal targeted testing, MPS IVA should remain in the differential diagnosis. Third, that whole exome sequencing represents a viable diagnostic platform for evaluation of patients with unknown skeletal or metabolic disease.

  17. IVA. Improving Vocational Administration. Final Report.

    ERIC Educational Resources Information Center

    EPD Consortium D, Richardson, TX.

    The Texas Improving Vocational Administration (IVA) project was conceived to improve preservice and inservice programs for vocational education administrators. Primary objectives were to (1) develop a method, including a survey, to determine existing inservice and preservice administrative training program competencies; (2) determine, using the…

  18. Determination and validation of chikusetsusaponin IVa in rat plasma by UPLC-MS/MS and its application to pharmacokinetic study.

    PubMed

    Wang, Ying; Liu, Shi-Ping; Guo, Mei-Hua; Wang, Zhuo

    2016-09-01

    A novel, sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometric method for the quantification of chikusetsusaponin IVa (CHS-IVa) in rat plasma was established and validated. Plasma samples were pre-treated by precipitation of protein with acetonitrile and chromatographed on a Waters Symmetry C18 analytical column (4.6 × 50 mm, i.d., 3.5 μm) using a mobile phase consisting of methanol and water containing 0.05% formic acid (55:45, v/v) at a flow rate of 0.4 mL/min. The deprotonated molecular ions [M - H](-) were employed in electrospray negative ionization mode and selected reaction monitoring transitions were performed for detection. The calibration curves exhibited good linearity (r > 0.99) over the range of 0.5-1000 ng/mL for CHS-IVa. The recoveries of CHS-IVa were >92.5% and exhibited no severe matrix effect. This method was successfully applied in the pharmacokinetic study of CHS-IVa in rats. For oral administration, the plasma concentrations of CHS-IVa increased to a peak value at 0.35 ± 0.14 h, followed by a gradual decrease to the lower limit of quantitation in 24 h. For intravenous administration, the plasma concentrations of CHS-IVa decreased quickly (t1/2 , 1.59 ± 0.25 h). The absolute bioavailability of CHS-IVa in rats was 8.63%. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Physiological and glycomic characterization of N-acetylglucosaminyltransferase-IVa and -IVb double deficient mice

    PubMed Central

    Takamatsu, Shinji; Antonopoulos, Aristotelis; Ohtsubo, Kazuaki; Ditto, David; Chiba, Yasunori; Le, Dzung T.; Morris, Howard R.; Haslam, Stuart M.; Dell, Anne; Marth, Jamey D.; Taniguchi, Naoyuki

    2010-01-01

    N-Acetylglucosaminyltransferase-IV (GnT-IV) has two isoenzymes, GnT-IVa and GnT-IVb, which initiate the GlcNAcβ1-4 branch synthesis on the Manα1-3 arm of the N-glycan core thereby increasing N-glycan branch complexity and conferring endogenous lectin binding epitopes. To elucidate the physiological significance of GnT-IV, we engineered and characterized GnT-IVb-deficient mice and further generated GnT-IVa/-IVb double deficient mice. In wild-type mice, GnT-IVa expression is restricted to gastrointestinal tissues, whereas GnT-IVb is broadly expressed among organs. GnT-IVb deficiency induced aberrant GnT-IVa expression corresponding to the GnT-IVb distribution pattern that might be attributed to increased Ets-1, which conceivably activates the Mgat4a promoter, and thereafter preserved apparent GnT-IV activity. The compensative GnT-IVa expression might contribute to amelioration of the GnT-IVb-deficient phenotype. GnT-IVb deficiency showed mild phenotypic alterations in hematopoietic cell populations and hemostasis. GnT-IVa/-IVb double deficiency completely abolished GnT-IV activity that resulted in the disappearance of the GlcNAcβ1-4 branch on the Manα1-3 arm that was confirmed by MALDI-TOF MS and GC-MS linkage analyses. Comprehensive glycomic analyses revealed that the abundance of terminal moieties was preserved in GnT-IVa/-IVb double deficiency that was due to the elevated expression of glycosyltransferases regarding synthesis of terminal moieties. Thereby, this may maintain the expression of glycan ligands for endogenous lectins and prevent cellular dysfunctions. The fact that the phenotype of GnT-IVa/-IVb double deficiency largely overlapped that of GnT-IVa single deficiency can be attributed to the induced glycomic compensation. This is the first report that mammalian organs have highly organized glycomic compensation systems to preserve N-glycan branch complexity. PMID:20015870

  20. Physiological and glycomic characterization of N-acetylglucosaminyltransferase-IVa and -IVb double deficient mice.

    PubMed

    Takamatsu, Shinji; Antonopoulos, Aristotelis; Ohtsubo, Kazuaki; Ditto, David; Chiba, Yasunori; Le, Dzung T; Morris, Howard R; Haslam, Stuart M; Dell, Anne; Marth, Jamey D; Taniguchi, Naoyuki

    2010-01-01

    N-Acetylglucosaminyltransferase-IV (GnT-IV) has two isoenzymes, GnT-IVa and GnT-IVb, which initiate the GlcNAcbeta1-4 branch synthesis on the Manalpha1-3 arm of the N-glycan core thereby increasing N-glycan branch complexity and conferring endogenous lectin binding epitopes. To elucidate the physiological significance of GnT-IV, we engineered and characterized GnT-IVb-deficient mice and further generated GnT-IVa/-IVb double deficient mice. In wild-type mice, GnT-IVa expression is restricted to gastrointestinal tissues, whereas GnT-IVb is broadly expressed among organs. GnT-IVb deficiency induced aberrant GnT-IVa expression corresponding to the GnT-IVb distribution pattern that might be attributed to increased Ets-1, which conceivably activates the Mgat4a promoter, and thereafter preserved apparent GnT-IV activity. The compensative GnT-IVa expression might contribute to amelioration of the GnT-IVb-deficient phenotype. GnT-IVb deficiency showed mild phenotypic alterations in hematopoietic cell populations and hemostasis. GnT-IVa/-IVb double deficiency completely abolished GnT-IV activity that resulted in the disappearance of the GlcNAcbeta1-4 branch on the Manalpha1-3 arm that was confirmed by MALDI-TOF MS and GC-MS linkage analyses. Comprehensive glycomic analyses revealed that the abundance of terminal moieties was preserved in GnT-IVa/-IVb double deficiency that was due to the elevated expression of glycosyltransferases regarding synthesis of terminal moieties. Thereby, this may maintain the expression of glycan ligands for endogenous lectins and prevent cellular dysfunctions. The fact that the phenotype of GnT-IVa/-IVb double deficiency largely overlapped that of GnT-IVa single deficiency can be attributed to the induced glycomic compensation. This is the first report that mammalian organs have highly organized glycomic compensation systems to preserve N-glycan branch complexity.

  1. Crystal structures of Boc-D- and L-Iva-L-Pro-OBzl: unturned conformation of Aib-Pro sequence unaffected by replacement of Me with Et in Aib.

    PubMed

    Kawai, M; Omori, Y; Yamamura, H; Butsugan, Y; Taga, T; Miwa, Y

    1993-08-01

    The crystal structures of the isovaline (Iva) containing dipeptides, Boc-D-Iva-L-Pro-OBzl and Boc-L-Iva-L-Pro-OBzl, were determined by x-ray diffraction. The diastereomeric peptides were shown to adopt unturned conformations closely similar to each other (phi Iva 52 degrees, psi Iva 46 degrees, phi Pro -65 degrees, and psi Pro 143 degrees for D-Iva-L-Pro sequence and phi Iva 52 degrees, psi Iva 44 degrees, phi Pro -63 degrees, and psi Pro 148 degrees for L-Iva-L-Pro sequence). The Pro ring of each peptide was in C gamma-endo conformation. The unusually large angle CIva-NPro-C delta Pro values (131 degrees in both peptides) were observed, that was due to steric repulsion between the delta-methylene of Pro and the alkyl side chain of Iva residue. These conformations were essentially the same as that of the corresponding alpha-aminoisobutyric acid (Aib)-containing peptide Boc-Aib-L-Pro-OBzl. The result has demonstrated that replacement of either one of the two methyl groups of the Aib residue in Boc-Aib-L-Pro-OBzl with an ethyl group does not cause any significant change in the unturned conformation of the dipeptide.

  2. Floodplain evolution in a confluence zone: Paraná and Ivaí rivers, Brazil

    NASA Astrophysics Data System (ADS)

    Morais, Eduardo Souza de; Santos, Manoel Luis dos; Cremon, Édipo Henrique; Stevaux, José Cândido

    2016-03-01

    In this study we investigated floodplain development at the confluence of the Paraná and Ivaí rivers, Brazil. We evaluated paleochannels with sedimentary facies and morphometry from cartographic products, which enabled us to identify compartments that indicate homologous morphogenesis. These results contributed to the distinction in the floodplain of areas reworked by the Paraná, Ivaí, or both river systems. Additionally, investigations that included dating deposits on the terrace that borders the floodplain and an alluvial fan (also in contact with the floodplain) reinforced the interpretation of the fluvial landscape. The identified stages of geomorphological evolution demonstrated the existence of a paleoconfluence of the Paraná and Ivaí rivers during the late Pleistocene that was located 6 km upstream from the current confluence. This paleoconfluence displays a different configuration in relation to the current confluence, and its features resemble and contribute to understanding the former braided channel pattern of the Paraná River. The abandonments of the Paraná River channels identified in this study were initial and crucial process in the development of the floodplain. This channel change favored the formation of extensive wetlands and consequently the confluence migration, which resulted in the fluvial reworking indicated by the paleochannels of the Ivaí River. Another implication from the confluence migration was a base level fall, which contributed to maintaining the stability of the Ivaí River and its embedded meanders. In addition, investigations of an alluvial fan in the Paraná River valley provided evidence of massive deposition of sediments from a tributary of the Ivaí River onto the floodplain, which is associated with a regional dry period in the late Holocene as well as neotectonic control.

  3. Structural regions of MD-2 that determine the agonist-antagonist activity of lipid IVa.

    PubMed

    Muroi, Masashi; Tanamoto, Ken-ichi

    2006-03-03

    A cell surface receptor complex consisting of CD14, Toll-like receptor (TLR4), and MD-2 recognizes lipid A, the active moiety of lipopolysaccharide (LPS). Escherichia coli-type lipid A, a typical lipid A molecule, potently activates both human and mouse macrophage cells, whereas the lipid A precursor, lipid IVa, activates mouse macrophages but is inactive and acts as an LPS antagonist in human macrophages. This animal species-specific activity of lipid IVa involves the species differences in MD-2 structure. We explored the structural region of MD-2 that determines the agonistic and antagonistic activities of lipid IVa to induce nuclear factor-kappaB activation. By expressing human/mouse chimeric MD-2 together with mouse CD14 and TLR4 in human embryonic kidney 293 cells, we found that amino acid regions 57-79 and 108-135 of MD-2 determine the species-specific activity of lipid IVa. We also showed that the replacement of Thr(57), Val(61), and Glu(122) of mouse MD-2 with corresponding human MD-2 sequence or alanines impaired the agonistic activity of lipid IVa, and antagonistic activity became evident. These mutations did not affect the activation of nuclear factor-kappaB, TLR4 oligomerization, and inducible phosphorylation of IkappaBalpha in response to E. coli-type lipid A. These results indicate that amino acid residues 57, 61, and 122 of mouse MD-2 are critical to determine the agonist-antagonist activity of lipid IVa and suggest that these amino acid residues may be involved in the discrimination of lipid A structure.

  4. Group IVA phospholipase A2-associated production of MMP-9 in macrophages and formation of atherosclerotic lesions.

    PubMed

    Ii, Hiromi; Hontani, Naoya; Toshida, Issei; Oka, Mayuko; Sato, Takashi; Akiba, Satoshi

    2008-03-01

    Matrix metalloproteinase-9 (MMP-9) is involved in atherogenesis, and the production of MMP-9 in macrophages is considered to be mediated by the arachidonic acid cascade. The present study examined the possible involvement of group IVA phospholipase A2 (IVA-PLA2), a key enzyme in the arachidonic acid cascade, in the production of MMP-9 induced by oxidized low-density lipoprotein (oxLDL) in macrophages and high-fat diet-induced formation of atherosclerotic lesions using IVA-PLA2-deficient mice (C57BL/6 background). In wild-type mouse peritoneal macrophages, oxLDL induced an increase in MMP-9 in the culture medium. The oxLDL-promoted production of MMP-9 was markedly reduced in IVA-PLA2-deficient macrophages compared to wild-type macrophages. Feeding of wild-type mice with a high-fat diet caused the formation of early atherosclerotic lesions in the aortic root with increases in MMP-9 and macrophages in the lesions and with higher serum levels of total cholesterol. Such lesions were apparently less severe in IVA-PLA2-deficient mice fed a high-fat diet, despite higher total cholesterol levels. Under the conditions, a high-fat diet reduced the serum levels of high-density lipoprotein-cholesterol (HDL-C) in wild-type mice. However, IVA-PLA2-deficient mice fed a high-fat diet were protected against the decrease in HDL-C levels. The present results suggest that IVA-PLA2 is involved in the oxLDL-induced production of MMP-9 in macrophages and the high-fat diet-induced formation of early atherosclerotic lesions. The protection against the lesions in IVA-PLA2-deficient mice may be ascribable, in part, to the impaired production of MMP-9 and/or the maintained levels of HDL-C.

  5. PHASE I SINGLE CELL ELECTROLYZER TEST RESULTS

    SciTech Connect

    Steimke, J; Timothy Steeper, T

    2008-08-05

    This document reports the results of Phase I Single Cell testing of an SO{sub 2}-Depolarized Water Electrolyzer. Testing was performed primarily during the first quarter of FY 2008 at the Savannah River National Laboratory (SRNL) using an electrolyzer cell designed and built at SRNL. Other facility hardware were also designed and built at SRNL. This test further advances this technology for which work began at SRNL in 2005. This research is valuable in achieving the ultimate goal of an economical hydrogen production process based on the Hybrid Sulfur (HyS) Cycle. The focus of this work was to conduct single cell electrolyzer tests to further develop the technology of SO{sub 2}-depolarized electrolysis as part of the HyS Cycle. The HyS Cycle is a hybrid thermochemical cycle that may be used in conjunction with advanced nuclear reactors or centralized solar receivers to produce hydrogen by water-splitting. Like all other sulfur-based cycles, HyS utilizes the high temperature thermal decomposition of sulfuric acid to produce oxygen and regenerate sulfur dioxide. The unique aspect of HyS is the generation of hydrogen in a water electrolyzer that is operated under conditions where dissolved sulfur dioxide depolarizes the anodic reaction, resulting in substantial voltage reduction. Low cell voltage is essential for both thermodynamic efficiency and hydrogen cost. Sulfur dioxide is oxidized at the anode, producing sulfuric acid that is sent to the high temperature acid decomposition portion of the cycle. The electrolyzer cell uses the membrane electrode assembly (MEA) concept. The anode and cathode are formed by spraying platinum containing catalyst on both sides of a Proton Exchange Membrane (PEM). In most testing the material of the PEM was NafionR. The electrolyzer cell active area can be as large as 54.8 cm{sup 2}. Feed to the anode of the electrolyzer is a sulfuric acid solution containing sulfur dioxide. The partial pressure of sulfur dioxide could be varied in the

  6. Inhibitory effects of Chikusetsusaponin IVa on lipopolysaccharide-induced pro-inflammatory responses in THP-1 cells.

    PubMed

    Wang, H; Qi, J; Li, L; Wu, T; Wang, Y; Wang, X; Ning, Q

    2015-09-01

    This study investigated anti-inflammatory effects and possible mechanisms of Chikusetsusaponin IVa (Chi IVa), one of the main bioactive components in saponins from Panacis japonica (SPJ), which is used in traditional Tujia and Hmong Chinese medicine. To this end, changes in the inflammatory profiles of lipopolysacchride (LPS)-stimulated phrobol 12-myristate 13-acetate(PMA)-differented THP-1 macrophages were evaluated following Chi IVa treatment. The results showed that Chi IVa markedly decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) at both the mRNA and protein level, which proved to be dose-dependent. Further studies revealed that Chi IVa strongly suppressed NF-κB activation and downregulated the phosphorylation of ERK, p38, and JNK. Our present study demonstrates that Chi IVa suppresses the production of iNOS, COX-2, IL-1β, IL-6, and TNF-α in LPS-stimulated THP-1 cells likely by inhibiting NF-κB activation and ERK, JNK, and p38 signal pathway phosphorylation. © The Author(s) 2015.

  7. Therapeutic effect of phytoecdysteroids rich extract from Ajuga iva on alloxan induced diabetic rats liver, kidney and pancreas.

    PubMed

    Hamden, Khaled; Ayadi, Fatma; Jamoussi, Kamel; Masmoudi, Hatem; Elfeki, Abdelfattah

    2008-01-01

    In the current study, the effect of Ajuga iva extract on blood glucose, lipid profile, hepatic and renal toxicity and antioxidant enzyme activities in alloxan-induced diabetic rats was investigated. Diabetes was confirmed by measuring the glucoserua concentration 15 days after alloxan administration. Ajuga iva extract was administrated orally 3 weeks after alloxan injection. Our results investigate that Ajuga iva extract supplementation increased the levels of both enzymatic antioxidant (superoxide dismutase, catalase and glutathione peroxidase) and metals antioxidants (iron, copper, magnesium, calcium) and decreased lipid peroxidation level (TBARs). Besides Ajuga iva ameliorated diabetes provoked hepatic and renal toxicity appeared by a lower level in total and direct bilirubin, urea, creatinine, triglyceride (TG), cholesterol and a higher level in HDL-cholesterol. Besides, the activities of phosphatase alkalines (PAL), aspartate and lactate transaminase (AST & ALT) were decreased. The benefices effects of phytoecdysteroids of Ajuga iva confirmed by histological observation in pancreatic tissues. In conclusion, Ajuga iva phytoecdysteroids supplements seem to be beneficial for correcting the hyperglycemia and preventing diabetic complications in liver, pancreas and kidneys.

  8. An autoinhibitory conformation of the Bacillus subtilis spore coat protein SpoIVA prevents its premature ATP-independent aggregation.

    PubMed

    Castaing, Jean-Philippe; Lee, Scarlett; Anantharaman, Vivek; Ravilious, Geoffrey E; Aravind, L; Ramamurthi, Kumaran S

    2014-09-01

    Spores of Bacillus subtilis are dormant cell types that are formed when the bacterium encounters starvation conditions. Spores are encased in a shell, termed the coat, which is composed of approximately seventy different proteins and protects the spore's genetic material from environmental insults. The structural component of the basement layer of the coat is an exceptional cytoskeletal protein, termed SpoIVA, which binds and hydrolyzes ATP. ATP hydrolysis is utilized to drive a conformational change in SpoIVA that leads to its irreversible self-assembly into a static polymer in vitro. Here, we characterize the middle domain of SpoIVA, the predicted secondary structure of which resembles the chemotaxis protein CheX but, unlike CheX, does not harbor residues required for phosphatase activity. Disruptions in this domain did not abolish ATP hydrolysis, but resulted in mislocalization of the protein and reduction in sporulation efficiency in vivo. In vitro, disruptions in this domain prevented the ATP hydrolysis-driven conformational change in SpoIVA required for polymerization and led to the aggregation of SpoIVA into particles that did not form filaments. We propose a model in which SpoIVA initially assumes a conformation in which it inhibits its own aggregation into particles, and that ATP hydrolysis remodels the protein so that it assumes a polymerization-competent conformation.

  9. Vapor-liquid phase separator permeability results

    NASA Technical Reports Server (NTRS)

    Yuan, S. W. K.; Frederking, T. H. K.

    1981-01-01

    Continued studies are described in the area of vapor-liquid phase separator work with emphasis on permeabilities of porous sintered plugs (stainless steel, nominal pore size 2 micrometer). The temperature dependence of the permeability has been evaluated in classical fluid using He-4 gas at atmospheric pressure and in He-2 on the basis of a modified, thermosmotic permeability of the normal fluid.

  10. The antagonist activity of lipid IVa on the stimulation by lipid A of TNF-alpha production from canine blood mononuclear cells.

    PubMed

    Takasawa, Kenji; Kano, Rui; Maruyama, Haruhiko; Hasegawa, Atsuhiko; Kamata, Hiroshi

    2011-09-15

    Lipid A, the active component of lipopolysaccharide (LPS), exists in the outer membrane of Gram-negative bacteria and binds to the Toll-like receptor 4 (TLR4) and MD-2 complex. On the other hand, the synthetic precursor of Escherichia coli lipid A, tetraacylated lipid IVa, is an agonist for TLR4 and MD-2 complex in murine, equine and feline cells but is an antagonist for lipid A in human cells. The aim of the study was to examine the function of canine Toll-like receptor 4 (TLR4) and MD-2 complex on canine blood mononuclear cells (BMC), by analyzing lipid A- or lipid IVa-induction of TNF-α production from these cells in order to understand canine innate immune system. After 5-h culture of canine BMC with lipid A (lipid A culture) or lipid IVa (lipid IVa culture), the TNF-α, as determined by ELISA, had increased in the supernatants of the lipid A cultures in a dose-dependent manner, whereas the TNF-α was undetectable in supernatant of lipid IVa-treated cultures. The TNF-α was statistically significantly different between the lipid A and lipid IVa cultures (100 and 1000 ng/ml). TNF-α production from canine BMC was inhibited, in a lipid IVa-dose-dependent manner, when the BMC were pre-cultured with lipid IVa for 60 min and then cultured with lipid A for 5h, while in control BMC cultures production if TNF-α was unchanged. These results indicate that the TNF-α production stimulated by lipid A was competed out by pre-exposing the BMC to lipid IVa. Thus, lipid A is an agonist for TNF-α production in canine BMC, whereas lipid IVa appears to be an antagonist against this lipid A stimulation of canine BMC.

  11. Newberry Volcano EGS Demonstration - Phase I Results

    SciTech Connect

    Osborn, William L.; Petty, Susan; Cladouhos, Trenton T.; Iovenitti, Joe; Nofziger, Laura; Callahan, Owen; Perry, Douglas S.; Stern, Paul L.

    2011-10-23

    Phase I of the Newberry Volcano Enhanced Geothermal System (EGS) Demonstration included permitting, community outreach, seismic hazards analysis, initial microseismic array deployment and calibration, final MSA design, site characterization, and stimulation planning. The multi-disciplinary Phase I site characterization supports stimulation planning and regulatory permitting, as well as addressing public concerns including water usage and induced seismicity. A review of the project's water usage plan by an independent hydrology consultant found no expected impacts to local stakeholders, and recommended additional monitoring procedures. The IEA Protocol for Induced Seismicity Associated with Enhanced Geothermal Systems was applied to assess site conditions, properly inform stakeholders, and develop a comprehensive mitigation plan. Analysis of precision LiDAR elevation maps has concluded that there is no evidence of recent faulting near the target well. A borehole televiewer image log of the well bore revealed over three hundred fractures and predicted stress orientations. No natural, background seismicity has been identified in a review of historic data, or in more than seven months of seismic data recorded on an array of seven seismometers operating around the target well. A seismic hazards and induced seismicity risk assessment by an independent consultant concluded that the Demonstration would contribute no additional risk to residents of the nearest town of La Pine, Oregon. In Phase II of the demonstration, an existing deep hot well, NWG 55-29, will be stimulated using hydroshearing techniques to create an EGS reservoir. The Newberry Volcano EGS Demonstration is allowing geothermal industry and academic experts to develop, validate and enhance geoscience and engineering techniques, and other procedures essential to the expansion of EGS throughout the country. Successful development will demonstrate to the American public that EGS can play a significant role in

  12. A core origin for group IVA iron meteorites - A reply to Moren and Goldstein

    NASA Technical Reports Server (NTRS)

    Willis, J.; Wasson, J. T.

    1978-01-01

    Because uncertainties in experimental data are large, one has considerable latitude in choosing the input parameters needed to calculate iron meteorite cooling rates. The best way to test input parameters is by examining their ability to yield the observed properties of the meteorites. Our phase diagram yields fits to kamacite profiles that are superior to those based on the Moren-Goldstein phase diagram. Our method of allowing for the effect of P on the Ni diffusion coefficient takes into account the enhancement in this effect with decreasing temperature; Moren and Goldstein use a relationship derived for a temperature of 1100 C, well outside the 700-350 C range where kamacite growth occurs. Use of our input parameters yields cooling rates in IVA irons that are independent of composition, consistent with a core origin. Since the fractionation of siderophiles in group IVA also indicates a core origin, we conclude that this is the correct model for this group.

  13. A core origin for group IVA iron meteorites - A reply to Moren and Goldstein

    NASA Technical Reports Server (NTRS)

    Willis, J.; Wasson, J. T.

    1978-01-01

    Because uncertainties in experimental data are large, one has considerable latitude in choosing the input parameters needed to calculate iron meteorite cooling rates. The best way to test input parameters is by examining their ability to yield the observed properties of the meteorites. Our phase diagram yields fits to kamacite profiles that are superior to those based on the Moren-Goldstein phase diagram. Our method of allowing for the effect of P on the Ni diffusion coefficient takes into account the enhancement in this effect with decreasing temperature; Moren and Goldstein use a relationship derived for a temperature of 1100 C, well outside the 700-350 C range where kamacite growth occurs. Use of our input parameters yields cooling rates in IVA irons that are independent of composition, consistent with a core origin. Since the fractionation of siderophiles in group IVA also indicates a core origin, we conclude that this is the correct model for this group.

  14. Linkage of PRA models. Phase 1, Results

    SciTech Connect

    Smith, C.L.; Knudsen, J.K.; Kelly, D.L.

    1995-12-01

    The goal of the Phase I work of the ``Linkage of PRA Models`` project was to postulate methods of providing guidance for US Nuclear Regulator Commission (NRC) personnel on the selection and usage of probabilistic risk assessment (PRA) models that are best suited to the analysis they are performing. In particular, methods and associated features are provided for (a) the selection of an appropriate PRA model for a particular analysis, (b) complementary evaluation tools for the analysis, and (c) a PRA model cross-referencing method. As part of this work, three areas adjoining ``linking`` analyses to PRA models were investigated: (a) the PRA models that are currently available, (b) the various types of analyses that are performed within the NRC, and (c) the difficulty in trying to provide a ``generic`` classification scheme to groups plants based upon a particular plant attribute.

  15. Study of space shuttle EVA/IVA support requirements. Volume 1: Technical summary report

    NASA Technical Reports Server (NTRS)

    Copeland, R. J.; Wood, P. W., Jr.; Cox, R. L.

    1973-01-01

    Results are summarized which were obtained for equipment requirements for the space shuttle EVA/IVA pressure suit, life support system, mobility aids, vehicle support provisions, and energy 4 support. An initial study of tasks, guidelines, and constraints and a special task on the impact of a 10 psia orbiter cabin atmosphere are included. Supporting studies not related exclusively to any one group of equipment requirements are also summarized. Representative EVA/IVA task scenarios were defined based on an evaluation of missions and payloads. Analysis of the scenarios resulted in a total of 788 EVA/IVA's in the 1979-1990 time frame, for an average of 1.3 per shuttle flight. Duration was estimated to be under 4 hours on 98% of the EVA/IVA's, and distance from the airlock was determined to be 70 feet or less 96% of the time. Payload water vapor sensitivity was estimated to be significant on 9%-17% of the flights. Further analysis of the scenarios was carried out to determine specific equipment characteristics, such as suit cycle and mobility requirements.

  16. Group IVA irons: New constraints on the crystallization and cooling history of an asteroidal core with a complex history

    NASA Astrophysics Data System (ADS)

    McCoy, T. J.; Walker, R. J.; Goldstein, J. I.; Yang, J.; McDonough, W. F.; Rumble, D.; Chabot, N. L.; Ash, R. D.; Corrigan, C. M.; Michael, J. R.; Kotula, P. G.

    2011-11-01

    We report analyses of 14 group IVA iron meteorites, and the ungrouped but possibly related, Elephant Moraine (EET) 83230, for siderophile elements by laser ablation ICP-MS and isotope dilution. EET was also analyzed for oxygen isotopic composition and metallographic structure, and Fuzzy Creek, currently the IVA with the highest Ni concentration, was analyzed for metallographic structure. Highly siderophile elements (HSE) Re, Os and Ir concentrations vary by nearly three orders of magnitude over the entire range of IVA irons, while Ru, Pt and Pd vary by less than factors of five. Chondrite normalized abundances of HSE form nested patterns consistent with progressive crystal-liquid fractionation. Attempts to collectively model the HSE abundances resulting from fractional crystallization achieved best results for 3 wt.% S, compared to 0.5 or 9 wt.% S. Consistent with prior studies, concentrations of HSE and other refractory siderophile elements estimated for the bulk IVA core and its parent body are in generally chondritic proportions. Projected abundances of Pd and Au, relative to more refractory HSE, are slightly elevated and modestly differ from L/LL chondrites, which some have linked with group IVA, based on oxygen isotope similarities. Abundance trends for the moderately volatile and siderophile element Ga cannot be adequately modeled for any S concentration, the cause of which remains enigmatic. Further, concentrations of some moderately volatile and siderophile elements indicate marked, progressive depletions in the IVA system. However, if the IVA core began crystallization with ˜3 wt.% S, depletions of more volatile elements cannot be explained as a result of prior volatilization/condensation processes. The initial IVA core had an approximately chondritic Ni/Co ratio, but a fractionated Fe/Ni ratio of ˜10, indicates an Fe-depleted core. This composition is most easily accounted for by assuming that the surrounding silicate shell was enriched in iron

  17. Crystal structure and kinetic mechanism of aminoglycoside phosphotransferase-2″-IVa

    PubMed Central

    Toth, Marta; Frase, Hilary; Antunes, Nuno Tiago; Smith, Clyde A; Vakulenko, Sergei B

    2010-01-01

    Acquired resistance to aminoglycoside antibiotics primarily results from deactivation by three families of aminoglycoside-modifying enzymes. Here, we report the kinetic mechanism and structure of the aminoglycoside phosphotransferase 2″-IVa (APH(2″)-IVa), an enzyme responsible for resistance to aminoglycoside antibiotics in clinical enterococcal and staphylococcal isolates. The enzyme operates via a Bi-Bi sequential mechanism in which the two substrates (ATP or GTP and an aminoglycoside) bind in a random manner. The APH(2″)-IVa enzyme phosphorylates various 4,6-disubstituted aminoglycoside antibiotics with catalytic efficiencies (kcat/Km) of 1.5 × 103 to 1.2 × 106 (M−1 s−1). The enzyme uses both ATP and GTP as the phosphate source, an extremely rare occurrence in the phosphotransferase and protein kinase enzymes. Based on an analysis of the APH(2″)-IVa structure, two overlapping binding templates specifically tuned for hydrogen bonding to either ATP or GTP have been identified and described. A detailed understanding of the structure and mechanism of the GTP-utilizing phosphotransferases is crucial for the development of either novel aminoglycosides or, more importantly, GTP-based enzyme inhibitors which would not be expected to interfere with crucial ATP-dependent enzymes. PMID:20556826

  18. Elucidation of the MD-2/TLR4 interface required for signaling by lipid IVa.

    PubMed

    Walsh, Catherine; Gangloff, Monique; Monie, Tom; Smyth, Tomoko; Wei, Bin; McKinley, Trevelyan J; Maskell, Duncan; Gay, Nicholas; Bryant, Clare

    2008-07-15

    LPS signals through a membrane bound-complex of the lipid binding protein MD-2 and the receptor TLR4. In this study we identify discrete regions in both MD-2 and TLR4 that are required for signaling by lipid IVa, an LPS derivative that is an agonist in horse but an antagonist in humans. We show that changes in the electrostatic surface potential of both MD-2 and TLR4 are required in order that lipid IVa can induce signaling. In MD-2, replacing horse residues 57-66 and 82-89 with the equivalent human residues confers a level of constitutive activity on horse MD-2, suggesting that conformational switching in this protein is likely to be important in ligand-induced activation of MD-2/TLR4. We identify leucine-rich repeat 14 in the C terminus of TLR4 as essential for lipid IVa activation of MD-2/TLR4. Remarkably, we identify a single residue in the glycan-free flank of the horse TLR4 solenoid that confers the ability to signal in response to lipid IVa. These results suggest a mechanism of signaling that involves crosslinking mediated by both MD-2-receptor and receptor-receptor contacts in a model that shows striking similarities to the recently published structure (Cell 130: 1071-1082) of the ligand-bound TLR1/2 ectodomain heterodimer.

  19. Enzyme Replacement in a Human Model of Mucopolysaccharidosis IVA In Vitro and Its Biodistribution in the Cartilage of Wild Type Mice

    PubMed Central

    Dvorak-Ewell, Melita; Wendt, Dan; Hague, Chuck; Christianson, Terri; Koppaka, Vish; Crippen, Danielle; Kakkis, Emil; Vellard, Michel

    2010-01-01

    Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), an enzyme that degrades keratan sulfate (KS). Currently no therapy for MPS IVA is available. We produced recombinant human (rh)GALNS as a potential enzyme replacement therapy for MPS IVA. Chinese hamster ovary cells stably overexpressing GALNS and sulfatase modifying factor-1 were used to produce active (∼2 U/mg) and pure (≥97%) rhGALNS. The recombinant enzyme was phosphorylated and was dose-dependently taken up by mannose-6-phosphate receptor (Kuptake = 2.5 nM), thereby restoring enzyme activity in MPS IVA fibroblasts. In the absence of an animal model with a skeletal phenotype, we established chondrocytes isolated from two MPS IVA patients as a disease model in vitro. MPS IVA chondrocyte GALNS activity was not detectable and the cells exhibited KS storage up to 11-fold higher than unaffected chondrocytes. MPS IVA chondrocytes internalized rhGALNS into lysosomes, resulting in normalization of enzyme activity and decrease in KS storage. rhGALNS treatment also modulated gene expression, increasing expression of chondrogenic genes Collagen II, Collagen X, Aggrecan and Sox9 and decreasing abnormal expression of Collagen I. Intravenous administration of rhGALNS resulted in biodistribution throughout all layers of the heart valve and the entire thickness of the growth plate in wild-type mice. We show that enzyme replacement therapy with recombinant human GALNS results in clearance of keratan sulfate accumulation, and that such treatment ameliorates aberrant gene expression in human chondrocytes in vitro. Penetration of the therapeutic enzyme throughout poorly vascularized, but clinically relevant tissues, including growth plate cartilage and heart valve, as well as macrophages and hepatocytes in wild-type mouse, further supports development of rhGALNS as enzyme replacement therapy for MPS IVA. PMID:20808938

  20. Enzyme replacement in a human model of mucopolysaccharidosis IVA in vitro and its biodistribution in the cartilage of wild type mice.

    PubMed

    Dvorak-Ewell, Melita; Wendt, Dan; Hague, Chuck; Christianson, Terri; Koppaka, Vish; Crippen, Danielle; Kakkis, Emil; Vellard, Michel

    2010-08-16

    Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), an enzyme that degrades keratan sulfate (KS). Currently no therapy for MPS IVA is available. We produced recombinant human (rh)GALNS as a potential enzyme replacement therapy for MPS IVA. Chinese hamster ovary cells stably overexpressing GALNS and sulfatase modifying factor-1 were used to produce active ( approximately 2 U/mg) and pure (>or=97%) rhGALNS. The recombinant enzyme was phosphorylated and was dose-dependently taken up by mannose-6-phosphate receptor (K(uptake) = 2.5 nM), thereby restoring enzyme activity in MPS IVA fibroblasts. In the absence of an animal model with a skeletal phenotype, we established chondrocytes isolated from two MPS IVA patients as a disease model in vitro. MPS IVA chondrocyte GALNS activity was not detectable and the cells exhibited KS storage up to 11-fold higher than unaffected chondrocytes. MPS IVA chondrocytes internalized rhGALNS into lysosomes, resulting in normalization of enzyme activity and decrease in KS storage. rhGALNS treatment also modulated gene expression, increasing expression of chondrogenic genes Collagen II, Collagen X, Aggrecan and Sox9 and decreasing abnormal expression of Collagen I. Intravenous administration of rhGALNS resulted in biodistribution throughout all layers of the heart valve and the entire thickness of the growth plate in wild-type mice. We show that enzyme replacement therapy with recombinant human GALNS results in clearance of keratan sulfate accumulation, and that such treatment ameliorates aberrant gene expression in human chondrocytes in vitro. Penetration of the therapeutic enzyme throughout poorly vascularized, but clinically relevant tissues, including growth plate cartilage and heart valve, as well as macrophages and hepatocytes in wild-type mouse, further supports development of rhGALNS as enzyme replacement therapy for MPS IVA.

  1. Fractionation Trends Among IVA Iron Meteorites: Contrasts with IIIAB Trends

    NASA Technical Reports Server (NTRS)

    Wasson, J. T.; Richardson, J. W.

    2001-01-01

    A neutron-activation study of 49 group-IVA irons shows much lower negative slopes on Ir-Au and Ir-As diagrams than observed in the larger magmatic group IIIAB. This difference seems to reflect the tendency of D(sub Ir), D(sub Au), and D(sub As) to increase with increasing S content. Contents of S and other volatiles are much lower in IVA irons than IIIAB irons. We show that both groups can be fit with Dx values that depend quadratically on S, with initial IVA S contents about 6X lower than those in IIIAB. The IVA scatter fields show a spread in Au or As at constant Ir that appears to reflect variations in the fraction of trapped melt between 0% and 30%. Copper shows an S-shaped trend that may reflect moderate positive and negative changes in D(sub Cu) as the magma evolved or, less likely, sampling variations in a broad band reflecting fractionation and trapping of melt. Gibeon, the largest IVA iron with a mass greater than 30 tons, shows an appreciable range in compositions consistent either with differences in the degree of magma crystallization or with differences in the content of trapped melt. A striking difference between IVA and IIIAB is observed in the Ir/Au ratios in the most Ir-rich irons in the groups; that in IVA is 40% lower than the IIIAB ratio, and lower than those in other iron-meteorite groups, The IVA Ir/Au ratio is about half the ratios in the chondrite groups. We examined three possible explanations of this anomaly: (1) the high-Ir irons contain large amounts of trapped melt: or (2) half of the IVA core (i.e., the first 50% to crystallize) is missing from the terrestrial set of IVA irons; or (3) the IVA magma formed by incomplete melting of the metal in the chondritic precursor material, with the metal that remained in the mantle having high Ir and low Au contents. Plausibility arguments favor the third possibility. The third scenario is the most plausible, but the second cannot be ruled out. We review recent evidence regarding the cooling rates

  2. Fractionation Trends Among IVA Iron Meteorites: Contrasts with IIIAB Trends

    NASA Technical Reports Server (NTRS)

    Wasson, J. T.; Richardson, J. W.

    2001-01-01

    A neutron-activation study of 49 group-IVA irons shows much lower negative slopes on Ir-Au and Ir-As diagrams than observed in the larger magmatic group IIIAB. This difference seems to reflect the tendency of D(sub Ir), D(sub Au), and D(sub As) to increase with increasing S content. Contents of S and other volatiles are much lower in IVA irons than IIIAB irons. We show that both groups can be fit with Dx values that depend quadratically on S, with initial IVA S contents about 6X lower than those in IIIAB. The IVA scatter fields show a spread in Au or As at constant Ir that appears to reflect variations in the fraction of trapped melt between 0% and 30%. Copper shows an S-shaped trend that may reflect moderate positive and negative changes in D(sub Cu) as the magma evolved or, less likely, sampling variations in a broad band reflecting fractionation and trapping of melt. Gibeon, the largest IVA iron with a mass greater than 30 tons, shows an appreciable range in compositions consistent either with differences in the degree of magma crystallization or with differences in the content of trapped melt. A striking difference between IVA and IIIAB is observed in the Ir/Au ratios in the most Ir-rich irons in the groups; that in IVA is 40% lower than the IIIAB ratio, and lower than those in other iron-meteorite groups, The IVA Ir/Au ratio is about half the ratios in the chondrite groups. We examined three possible explanations of this anomaly: (1) the high-Ir irons contain large amounts of trapped melt: or (2) half of the IVA core (i.e., the first 50% to crystallize) is missing from the terrestrial set of IVA irons; or (3) the IVA magma formed by incomplete melting of the metal in the chondritic precursor material, with the metal that remained in the mantle having high Ir and low Au contents. Plausibility arguments favor the third possibility. The third scenario is the most plausible, but the second cannot be ruled out. We review recent evidence regarding the cooling rates

  3. [Analysis of GALNS gene mutation in thirty-eight Chinese patients with mucopolysaccharidosis type IVA].

    PubMed

    Ye, Jun; Lei, Hong-lin; Zhang, Hui-wen; Qiu, Wen-juan; Han, Lian-shu; Wang, Yu; Li, Xiao-yan; Gu, Xue-fan

    2013-06-01

    Mucopolysaccharidosis (MPS) type IVA (MPS IVA) is an autosomal recessive lysosomal storage disease caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) needed to degrade glycosaminoglycanes (GAGs), accumulation of GAGs in the tissue resulting in disorder of function. So far, the small number of articles about clinical study of Chinese MPS IVA were published and only one paper about gene mutation analysis was published. This study aimed to investigate the mutation spectrum and characteristic of GALNS gene in Chinese patients with MPS IVA who were diagnosed in our hospital. Thirty-eight patients from 36 families (male 17, female 21) were diagnosed as MPS IVA by GALNS activity determination [(0.85 ± 1.33) nmol/(17 h·mg)] and clinical symptoms during 2006-2012. The average age of diagnosis was (5.7 ± 3.6) years. Mutation analysis of GALNS gene performed performed by PCR-direct DNA sequencing for 38 patients. PCR-restriction fragment length polymorphism analysis was used for validating novel mutation, and also to assess amino acid conservation for novel missense variants in five different species. PolyPhen-2 tool was used to predict the possible impact of missense mutations on the structure and function of the human GALNS protein, etc. Analysis of GALNS activity and gene mutation in amniotic fluid were performed to provide the prenatal diagnosis for some families with MPS type IVA. (1) Thirty-eight kinds of mutation in GALNS gene were identified in 38 patients of them, 71% were missense mutations. p. M318R was a hot-spot mutation (21%) tested. Five kinds of mutation i.e., p. P163H, p.G168L, p. A324E, p. L366P and p. F452L were only found in Chinese patients with MPS IVA. Eighteen kinds of novel mutation were detected including p. E315K, p.G304D, p.R251Q, p.Y240C, p.G161E, p.N32D, p.L390P, p. D60E, p. P420S, W403C/T404S, p.L454P, for p.W405X, p. M1I, c.409_ c.420del12, c.1176_1178del3, c.1046delG, c.1188delG and IVS9-2A>C. (2) The polymorphism of

  4. GALNS mutations in Indian patients with mucopolysaccharidosis IVA.

    PubMed

    Bidchol, Abdul Mueed; Dalal, Ashwin; Shah, Hitesh; S, Suryanarayana; Nampoothiri, Sheela; Kabra, Madhulika; Gupta, Neerja; Danda, Sumita; Gowrishankar, Kalpana; Phadke, Shubha R; Kapoor, Seema; Kamate, Mahesh; Verma, I C; Puri, Ratna Dua; Sankar, V H; Devi, A Radha Rama; Patil, S J; Ranganath, Prajnya; Jain, S Jamal Md Nurul; Agarwal, Meenal; Singh, Ankur; Mishra, Pallavi; Tamhankar, Parag M; Gopinath, Puthiya Mundyat; Nagarajaram, H A; Satyamoorthy, Kapaettu; Girisha, Katta Mohan

    2014-11-01

    Mucopolysaccharidosis IV A (Morquio syndrome A, MPS IVA) is a lysosomal storage disease caused by the deficiency of N-acetylgalactosamine-6-sulfatase (GALNS). The mutation spectrum in this condition is yet to be determined in Indians. We aimed to analyze the mutations in the GALNS gene in Asian Indians with MPS IVA. All the exons and the adjacent intronic regions of the gene were amplified and sequenced in sixty-eight unrelated Indian families. We identified 136 mutant alleles comprising of 40 different mutations. We report twenty-two novel mutations that comprise of seventeen missense (p.Asn32Thr, p.Leu36Arg, p.Pro52Leu, p.Pro77Ser, p.Cys79Arg, p.His142Pro, p.Tyr191Asp, p.Asn204Thr, p.Gly188Ser, p.Phe216Ser, p.Trp230Cys, p.Ala291Ser, p.Gly317Arg, p.His329Pro, p.Arg386Ser, p.Glu450Gly, p.Cys501Ser), three splice-site variants (c.120+1G>C, c.1003-3C>G, c.1139+1G>A), one nonsense mutation (p.Gln414*) and one frameshift mutation (p.Pro420Leufs*440). Eighteen mutations have been reported earlier. Among these p.Ser287Leu (8.82%), p.Phe216Ser (7.35%), p.Asn32Thr (6.61%) and p.Ala291Ser (5.88%) were the most frequent mutations in Indian patients but were rare in the mutational profiles reported in other populations. These results indicate that the Indian patients may have a distinct mutation spectrum compared to those of other populations. Mutant alleles in exon 1, 7 and 8 accounted for 44.8% of the mutations, and sequencing of these exons initially may be a cost-effective approach in Asian Indian patients. This is the largest study on molecular analysis of patients with MPS IVA reported in the literature, and the first report from India. © 2014 Wiley Periodicals, Inc.

  5. Final Technical Report: Results of Phase 1

    SciTech Connect

    Narang, David, J.; Hambrick, Joshua; Srinivasan, Devarajan; Ayyannar, Raja; O'Brien, Kathleen

    2011-09-28

    Arizona Public Service Company (APS) expects that by 2027, renewable energy will account for 6,590 GWh in energy consumption by its customers. While much of this future energy will come from large centrally-located power plants, distributed renewable energy, sited at the point of end-use will also play an important role in meeting the needs of APS customers and is expected to provide 1,734 GWh. With increasing penetration of residential and commercial photovoltaic (PV) systems at the point of end-use, PV power generation not only offsets the load, but could also cause significant shifts in power flow patterns through the distribution system, and could possibly cause reversal of flow through some branches of a distribution circuit. Significant changes to power flow introduced into existing distribution systems due to the increased amount of PV systems may cause operational issues, including over-voltage on the distribution feeder (loss of voltage regulation) and incorrect operation of control equipment, which may lead to an increase in the number of operations and related equipment wear that could affect equipment reliability and customer power quality. Additionally, connecting generation resources to a distribution feeder can introduce additional sources of short-circuit current to the distribution system. This could potentially result in increased short-circuit currents, potentially reaching damaging levels, causing protection desensitization and a potential loss of protection coordination. These effects may be further compounded by variability of PV production due to shading by clouds. The effects of these phenomena in distributed PV applications are not well understood, and there is a great need to characterize this variability. This project will contribute to understanding the effects of high-penetration solar electricity on the design and operation of distribution systems by demonstrating how a high penetration of PV systems affects grid operations of a

  6. Use MACES IVA Suit for EVA Mobility Evaluations

    NASA Technical Reports Server (NTRS)

    Watson, Richard D.

    2014-01-01

    The use of an Intra-Vehicular Activity (IVA) suit for a spacewalk or Extra-Vehicular Activity (EVA) was evaluated for mobility and usability in the Neutral Buoyancy Lab (NBL) environment. The Space Shuttle Advanced Crew Escape Suit (ACES) has been modified (MACES) to integrate with the Orion spacecraft. The first several missions of the Orion MPCV spacecraft will not have mass available to carry an EVA specific suit so any EVA required will have to be performed by the MACES. Since the MACES was not designed with EVA in mind, it was unknown what mobility the suit would be able to provide for an EVA or if a person could perform useful tasks for an extended time inside the pressurized suit. The suit was evaluated in multiple NBL runs by a variety of subjects including crewmembers with significant EVA experience. Various functional mobility tasks performed included: translation, body positioning, carrying tools, body stabilization, equipment handling, and use of tools. Hardware configurations included with and without TMG, suit with IVA gloves and suit with EVA gloves. Most tasks were completed on ISS mockups with existing EVA tools. Some limited tasks were completed with prototype tools on a simulated rocky surface. Major findings include: demonstration of the ability to weigh-out the suit, understanding the need to have subjects perform multiple runs prior to getting feedback, determination of critical sizing factors, and need for adjustment of suit work envelop. The early testing has demonstrated the feasibility of EVA's limited duration and limited scope. Further testing is required with more flight like tasking and constraints to validate these early results. If the suit is used for EVA, it will require mission specific modifications for umbilical management or PLSS integration, safety tether attachment, and tool interfaces. These evaluations are continuing through calendar year 2014.

  7. Study of space shuttle EVA/IVA support requirements. Volume 2: EVA/IVA tasks, guidelines, and constraints definition

    NASA Technical Reports Server (NTRS)

    Webbon, B. W.; Copeland, R. J.; Wood, P. W., Jr.; Cox, R. L.

    1973-01-01

    The guidelines for EVA and IVA tasks to be performed on the space shuttle are defined. In deriving tasks, guidelines, and constraints, payloads were first identified from the mission model. Payload requirements, together with man and manipulator capabilities, vehicle characteristics and operation, and safety considerations led to a definition of candidate tasks. Guidelines and constraints were also established from these considerations. Scenarios were established, and screening criteria, such as commonality of EVA and IVA activities, were applied to derive representative planned and unplanned tasks. The whole spectrum of credible contingency situations with a potential requirement for EVA/IVA was analyzed.

  8. Silica and Pyroxene in IVA Irons; Possible Formation of the IVA Magma by Impact Melting and Reduction of L-LL-Chondrite Materials Followed by Crystallization and Cooling

    NASA Technical Reports Server (NTRS)

    Wasson, John T.; Matsunami, Yoshiyuki; Rubin, Alan E.

    2006-01-01

    Group IVA is a large magmatic group of iron meteorites. The mean DELTA O-17 (= delta O-17 - 0.52(raised dot) delta O-18) of the silicates is approx. plus or minus 1.2%o, similar to the highest values in L chondrites and the lowest values in LL chondrites; delta O-18 values are also in the L/LL range. This strongly suggests that IVA irons formed by melting L-LL parental material, but the mean Ni content of IVA irons (83 mg/g) is much lower than that of a presumed L-LL parent (approx. 170 mg/g) and the low-Ca pyroxene present in two IVA meteorites is Fs13, much lower than the Fs20-29 values in L and LL chondrites. Thus, formation from L-LL precursors requires extensive addition of metallic Fe, probably produced by reduction of FeS and FeO. Group IVA also has S/Ni, Ga/Ni, and Ge/Ni ratios that are much lower than those in L-LL chondrites or any chondrite group that preserves nebular compositions, implying loss of these volatile elements during asteroidal processing. We suggest that these reduction and loss processes occurred near the surface of the asteroid during impact heating, and resulted partly from reduction by C, and partly from the thermal dissociation of FeS and FeO with loss of O and S. The hot (approx. 1770 K) low-viscosity melt quickly moved through channels in the porous asteroid to form a core. Two members of the IVA group, Sao Joao Nepomuceno (hereafter, SJN) and Steinbach, contain moderate amounts of orthopyroxene and silica, and minor amounts of low-Ca clinopyroxene. Even though SJN formed after approx. 26% crystallization and Steinbach formed after approx. 77% Crystallization of the IVA core, both could have originated within several tens of meters of the core-mantle interface if 99% of the crystallization occurred from the center outwards. Two other members of the group (Gibeon and Bishop Canyon) contain tabular tridymite, which we infer to have initially formed as veins deposited from a cooling SiO-rich vapor. The silicates were clearly introduced

  9. Silica and Pyroxene in IVA Irons; Possible Formation of the IVA Magma by Impact Melting and Reduction of L-LL-Chondrite Materials Followed by Crystallization and Cooling

    NASA Technical Reports Server (NTRS)

    Wasson, John T.; Matsunami, Yoshiyuki; Rubin, Alan E.

    2006-01-01

    Group IVA is a large magmatic group of iron meteorites. The mean DELTA O-17 (= delta O-17 - 0.52(raised dot) delta O-18) of the silicates is approx. plus or minus 1.2%o, similar to the highest values in L chondrites and the lowest values in LL chondrites; delta O-18 values are also in the L/LL range. This strongly suggests that IVA irons formed by melting L-LL parental material, but the mean Ni content of IVA irons (83 mg/g) is much lower than that of a presumed L-LL parent (approx. 170 mg/g) and the low-Ca pyroxene present in two IVA meteorites is Fs13, much lower than the Fs20-29 values in L and LL chondrites. Thus, formation from L-LL precursors requires extensive addition of metallic Fe, probably produced by reduction of FeS and FeO. Group IVA also has S/Ni, Ga/Ni, and Ge/Ni ratios that are much lower than those in L-LL chondrites or any chondrite group that preserves nebular compositions, implying loss of these volatile elements during asteroidal processing. We suggest that these reduction and loss processes occurred near the surface of the asteroid during impact heating, and resulted partly from reduction by C, and partly from the thermal dissociation of FeS and FeO with loss of O and S. The hot (approx. 1770 K) low-viscosity melt quickly moved through channels in the porous asteroid to form a core. Two members of the IVA group, Sao Joao Nepomuceno (hereafter, SJN) and Steinbach, contain moderate amounts of orthopyroxene and silica, and minor amounts of low-Ca clinopyroxene. Even though SJN formed after approx. 26% crystallization and Steinbach formed after approx. 77% Crystallization of the IVA core, both could have originated within several tens of meters of the core-mantle interface if 99% of the crystallization occurred from the center outwards. Two other members of the group (Gibeon and Bishop Canyon) contain tabular tridymite, which we infer to have initially formed as veins deposited from a cooling SiO-rich vapor. The silicates were clearly introduced

  10. Pilot Overmyer completes hygiene activities / demostrates IVA foot restraint

    NASA Technical Reports Server (NTRS)

    1982-01-01

    On middeck, Pilot Overmyer, drying his face with a towel from forward single tray personal item stowage locker, completes personal hygiene activities (shaving) and demostrates use of intravehicular activity (IVA) foot restraint on floor.

  11. Thirtieth Annual Congress on Veterinary Acupuncture: IVAS Report

    PubMed Central

    2005-01-01

    More than 155 participants from 25 countries attended the 30th Annual IVAS Congress, September 8–11, 2004 in Oostende, Belgium. The focus was on veterinary acupuncture (AP) and immunology, and the event was sponsored by the International Veterinary Acupuncture Society (IVAS). IVAS is a non-profit organization dedicated to promoting excellence in the practice of veterinary AP as an integral part of the total veterinary health care delivery system. The Society endeavors to establish uniformly high standards of veterinary AP through its educational programs and accreditation examination. IVAS seeks to integrate veterinary AP and the practice of Western veterinary science, while also noting that the science of veterinary AP does not overlook allied health systems, such as homeopathy, herbology, nutrition, chiropractic, kinesiology, etc. ().

  12. IVA: accurate de novo assembly of RNA virus genomes.

    PubMed

    Hunt, Martin; Gall, Astrid; Ong, Swee Hoe; Brener, Jacqui; Ferns, Bridget; Goulder, Philip; Nastouli, Eleni; Keane, Jacqueline A; Kellam, Paul; Otto, Thomas D

    2015-07-15

    An accurate genome assembly from short read sequencing data is critical for downstream analysis, for example allowing investigation of variants within a sequenced population. However, assembling sequencing data from virus samples, especially RNA viruses, into a genome sequence is challenging due to the combination of viral population diversity and extremely uneven read depth caused by amplification bias in the inevitable reverse transcription and polymerase chain reaction amplification process of current methods. We developed a new de novo assembler called IVA (Iterative Virus Assembler) designed specifically for read pairs sequenced at highly variable depth from RNA virus samples. We tested IVA on datasets from 140 sequenced samples from human immunodeficiency virus-1 or influenza-virus-infected people and demonstrated that IVA outperforms all other virus de novo assemblers. The software runs under Linux, has the GPLv3 licence and is freely available from http://sanger-pathogens.github.io/iva © The Author 2015. Published by Oxford University Press.

  13. Pilot Overmyer completes hygiene activities / demostrates IVA foot restraint

    NASA Technical Reports Server (NTRS)

    1982-01-01

    On middeck, Pilot Overmyer, drying his face with a towel from forward single tray personal item stowage locker, completes personal hygiene activities (shaving) and demostrates use of intravehicular activity (IVA) foot restraint on floor.

  14. Comparison of IVA and GIG-ICA in Brain Functional Network Estimation Using fMRI Data.

    PubMed

    Du, Yuhui; Lin, Dongdong; Yu, Qingbao; Sui, Jing; Chen, Jiayu; Rachakonda, Srinivas; Adali, Tulay; Calhoun, Vince D

    2017-01-01

    Spatial group independent component analysis (GICA) methods decompose multiple-subject functional magnetic resonance imaging (fMRI) data into a linear mixture of spatially independent components (ICs), some of which are subsequently characterized as brain functional networks. Group information guided independent component analysis (GIG-ICA) as a variant of GICA has been proposed to improve the accuracy of the subject-specific ICs estimation by optimizing their independence. Independent vector analysis (IVA) is another method which optimizes the independence among each subject's components and the dependence among corresponding components of different subjects. Both methods are promising in neuroimaging study and showed a better performance than the traditional GICA. However, the difference between IVA and GIG-ICA has not been well studied. A detailed comparison between them is demanded to provide guidance for functional network analyses. In this work, we employed multiple simulations to evaluate the performances of the two approaches in estimating subject-specific components and time courses under conditions of different data quality and quantity, varied number of sources generated and inaccurate number of components used in computation, as well as the presence of spatially subject-unique sources. We also compared the two methods using healthy subjects' test-retest resting-state fMRI data in terms of spatial functional networks and functional network connectivity (FNC). Results from simulations support that GIG-ICA showed better recovery accuracy of both components and time courses than IVA for those subject-common sources, and IVA outperformed GIG-ICA in component and time course estimation for the subject-unique sources. Results from real fMRI data suggest that GIG-ICA resulted in more reliable spatial functional networks and yielded higher and more robust modularity property of FNC, compared to IVA. Taken together, GIG-ICA is appropriate for estimating networks

  15. Lipid IVa incompletely activates MyD88-independent Toll-like receptor 4 signaling in mouse macrophage cell lines.

    PubMed

    Ogura, Norihiko; Muroi, Masashi; Sugiura, Yuka; Tanamoto, Ken-ichi

    2013-04-01

    We investigated the difference in the effect of synthetic lipid A compounds on MyD88-dependent and -independent Toll-like receptor 4 (TLR4) signaling in mouse macrophage cells. At higher concentrations, Escherichia coli-type hexa-acylated lipid A 506, Salmonella-type hepta-acylated lipid A 516, the lipid A precursor lipid IVa and monophosphoryl lipid A induced similar levels of production of the MyD88-dependent cytokine IL-1β although their potencies varied, whereas the maximum production of the MyD88-independent cytokine RANTES induced by lipid IVa was less than 50% that of other lipid A compounds. A maximum level of NF-κB activation, which is involved in IL-1β gene transcription, was also induced to a similar level by these four lipid A compounds, while the maximum level of IFN-β promoter activity induced during MyD88-independent signaling was also less than 50% for lipid IVa stimulation compared with other lipid A compounds. Early IκBα phosphorylation activated by MyD88-dependent signaling was similarly induced by 506 and lipid IVa, whereas lipid IVa barely stimulated the phosphorylation of IRF3, a MyD88-independent transcription factor, although efficient phosphorylation was observed with 506 stimulation. These results indicate that lipid IVa has limited activity toward MyD88-independent signaling of TLR4, in macrophage cell lines, despite having efficient activity in the MyD88-dependent pathway. © 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  16. Mucopolysaccharidosis type IVA: Common double deletion in the N-Acetylgalactosamine-6-sulfatase gene (GALNS)

    SciTech Connect

    Hori, Toshinori; Tomatsu, Shunji; Fukuda, Seiji

    1995-04-10

    Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by a deficiency in N-acetylgalactosamine-6-sulfatase (GALNS). We found two separate deletions of nearly 8.0 and 6.0 kb in the GALNS gene, including some exons. There are Alu repetitive elements near the breakpoints of the 8.0-kb deletion, and this deletion resulted from an Alu-Alu recombination. The other 6.0-kb deletion involved illegitimate recombinational events between incomplete short direct repeats of 8 bp at deletion breakpoints. The same rearrangement has been observed in a heteroallelic state in four unrelated patients. This is the first documentation of a common double deletion a gene that is not a member of a gene cluster. 39 refs., 5 figs.

  17. Physical and digital simulations for IVA robotics

    NASA Technical Reports Server (NTRS)

    Hinman, Elaine; Workman, Gary L.

    1992-01-01

    Space based materials processing experiments can be enhanced through the use of IVA robotic systems. A program to determine requirements for the implementation of robotic systems in a microgravity environment and to develop some preliminary concepts for acceleration control of small, lightweight arms has been initiated with the development of physical and digital simulation capabilities. The physical simulation facilities incorporate a robotic workcell containing a Zymark Zymate II robot instrumented for acceleration measurements, which is able to perform materials transfer functions while flying on NASA's KC-135 aircraft during parabolic manuevers to simulate reduced gravity. Measurements of accelerations occurring during the reduced gravity periods will be used to characterize impacts of robotic accelerations in a microgravity environment in space. Digital simulations are being performed with TREETOPS, a NASA developed software package which is used for the dynamic analysis of systems with a tree topology. Extensive use of both simulation tools will enable the design of robotic systems with enhanced acceleration control for use in the space manufacturing environment.

  18. Physical and digital simulations for IVA robotics

    NASA Technical Reports Server (NTRS)

    Hinman, Elaine; Workman, Gary L.

    1992-01-01

    Space based materials processing experiments can be enhanced through the use of IVA robotic systems. A program to determine requirements for the implementation of robotic systems in a microgravity environment and to develop some preliminary concepts for acceleration control of small, lightweight arms has been initiated with the development of physical and digital simulation capabilities. The physical simulation facilities incorporate a robotic workcell containing a Zymark Zymate II robot instrumented for acceleration measurements, which is able to perform materials transfer functions while flying on NASA's KC-135 aircraft during parabolic manuevers to simulate reduced gravity. Measurements of accelerations occurring during the reduced gravity periods will be used to characterize impacts of robotic accelerations in a microgravity environment in space. Digital simulations are being performed with TREETOPS, a NASA developed software package which is used for the dynamic analysis of systems with a tree topology. Extensive use of both simulation tools will enable the design of robotic systems with enhanced acceleration control for use in the space manufacturing environment.

  19. A phase I study afatinib/carboplatin/paclitaxel induction chemotherapy followed by standard chemoradiation in HPV-negative or high-risk HPV-positive locally advanced stage III/IVa/IVb head and neck squamous cell carcinoma

    PubMed Central

    Chung, Christine H.; Rudek, Michelle A.; Kang, Hyunseok; Marur, Shanthi; John, Pritish; Tsottles, Nancy; Bonerigo, Sarah; Veasey, Andy; Kiess, Ana; Quon, Harry; Cmelak, Anthony; Murphy, Barbara A.; Gilbert, Jill

    2015-01-01

    Introduction Afatinib is an ErbB family receptor inhibitor with efficacy in head and neck squamous cell carcinoma (HNSCC). A phase I trial was conducted to determine the maximally tolerated dose (MTD) of afatinib in combination with carboplatin and paclitaxel as induction chemotherapy (IC). Material and Methods Patients with newly diagnosed, locally advanced HPV-negative or HPV-positive HNSCC with a significant smoking history were enrolled. Afatinib alone was given daily for two weeks as lead-in and subsequently given with carboplatin AUC 6 mg/ml*min and paclitaxel 175 mg/m2 every 21 days as IC. Afatinib was started at a dose of 20 mg daily and dose escalated using a modified Fibonacci design. After completion of IC, afatinib was discontinued and patients received concurrent cisplatin 40 mg/m2 weekly and standard radiation. Toxicity was assessed using CTCAE version 4.0. Results Seven of nine patients completed afatinib lead-in and IC. Five patients had partial response and two patients had stable disease after IC. Dose level 1 (afatinib 20 mg) was well tolerated with one grade 3 (ALT elevation) and one grade 4 (neutropenia) toxicities. However, dose level 2 (afatinib 30 mg) was not well tolerated with nine grade 3 (pneumonia, abdominal pain, diarrhea, pancytopenia, and UTI), two grade 4 (sepsis) and one grade 5 (death) toxicities. Conclusions The MTD of afatinib given with carboplatin AUC 6 mg/ml*min and paclitaxel 175 mg/m2 is 20 mg daily. Combination of afatinib at doses higher than 20 mg with carboplatin and paclitaxel should be administered with caution due to the toxicities. PMID:26705063

  20. Mucopolysaccharidosis IVA: correlation between genotype, phenotype and keratan sulfate levels

    PubMed Central

    Dũng, Vu Chi; Tomatsu, Shunji; Montaño, Adriana M.; Gottesman, Gary; Bober, Michael B.; Mackenzie, William; Maeda, Miho; Mitchell, Grant A.; Suzuki, Yasuyuki; Orii, Tadao

    2013-01-01

    Mucopolysaccharidosis IVA (MPS IVA) is caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to systemic skeletal dysplasia because of excessive storage of keratan sulfate (KS) in chondrocytes. In an effort to determine a precise prognosis and personalized treatment, we aim to characterize clinical, biochemical, and molecular findings in MPS IVA patients, and to seek correlations between genotype, phenotype, and blood and urine KS levels. Mutation screening of GALNS gene was performed in 55 MPS IVA patients (severe: 36, attenuated: 13, undefined: 6) by genomic PCR followed by direct sequence analysis. Plasma and urine KS levels were measured by ELISA method. Genotype/phenotype/KS correlations were assessed when data were available. Fifty-three different mutations including 19 novel ones (41 missense, 2 nonsense, 4 small deletions, 1 insertion, and 5 splice-site) were identified in 55 patients and accounted for 93.6% of the analyzed mutant alleles. Thirty-nine mutations were associated with a severe phenotype and ten mutations with an attenuated one. Blood and urine KS concentrations in MPS IVA patients were age-dependent and markedly higher than those in age-matched normal controls. Plasma and urine KS levels in MPS IVA patients with the severe phenotype were higher than in those with an attenuated form. This study provides evidence for extensive allelic heterogeneity of MPS IVA. Accumulation of mutations as well as clinical descriptions and KS levels allow us to predict clinical severity more precisely and should be used for evaluation of responses to potential treatment options. PMID:23876334

  1. Mucopolysaccharidosis IVA: correlation between genotype, phenotype and keratan sulfate levels.

    PubMed

    Dũng, Vũ Chí; Tomatsu, Shunji; Montaño, Adriana M; Gottesman, Gary; Bober, Michael B; Mackenzie, William; Maeda, Miho; Mitchell, Grant A; Suzuki, Yasuyuki; Orii, Tadao

    2013-01-01

    Mucopolysaccharidosis IVA (MPS IVA) is caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to systemic skeletal dysplasia because of excessive storage of keratan sulfate (KS) in chondrocytes. In an effort to determine a precise prognosis and personalized treatment, we aim to characterize clinical, biochemical, and molecular findings in MPS IVA patients, and to seek correlations between genotype, phenotype, and blood and urine KS levels. Mutation screening of GALNS gene was performed in 55 MPS IVA patients (severe: 36, attenuated: 13, undefined: 6) by genomic PCR followed by direct sequence analysis. Plasma and urine KS levels were measured by ELISA method. Genotype/phenotype/KS correlations were assessed when data were available. Fifty-three different mutations including 19 novel ones (41 missense, 2 nonsense, 4 small deletions, 1 insertion, and 5 splice-site) were identified in 55 patients and accounted for 93.6% of the analyzed mutant alleles. Thirty-nine mutations were associated with a severe phenotype and ten mutations with an attenuated one. Blood and urine KS concentrations in MPS IVA patients were age-dependent and markedly higher than those in age-matched normal controls. Plasma and urine KS levels in MPS IVA patients with the severe phenotype were higher than in those with an attenuated form. This study provides evidence for extensive allelic heterogeneity of MPS IVA. Accumulation of mutations as well as clinical descriptions and KS levels allows us to predict clinical severity more precisely and should be used for evaluation of responses to potential treatment options. © 2013 Elsevier Inc. All rights reserved.

  2. Integrated thermal treatment system sudy: Phase 2, Results

    SciTech Connect

    Feizollahi, F.; Quapp, W.J.

    1995-08-01

    This report presents the second phase of a study on thermal treatment technologies. The study consists of a systematic assessment of nineteen thermal treatment alternatives for the contact-handled mixed low-level waste (MLLW) currently stored in the US Department of Energy complex. The treatment alternatives consist of widely varying technologies for safely destroying the hazardous organic components, reducing the volume, and preparing for final disposal of the MLLW. The alternatives considered in Phase 2 were innovative thermal treatments with nine types of primary processing units. Other variations in the study examined the effect of combustion gas, air pollution control system design, and stabilization technology for the treatment residues. The Phase 1 study, the results of which have been published as an interim report, examined ten initial thermal treatment alternatives. The Phase 2 systems were evaluated in essentially the same manner as the Phase 2 systems. The assumptions and methods were the same as for the Phase 1 study. The quantities, and physical and chemical compositions, of the input waste used in he Phase 2 systems differ from those in the Phase 1 systems, which were based on a preliminary waste input database developed at the onset of the Integrated Thermal Treatment System study. The inventory database used in the Phase 2 study incorporates the latest US Department of Energy information. All systems, both primary treatment systems and subsystem inputs, have now been evaluated using the same waste input (2,927 lb/hr).

  3. Long-term therapeutic efficacy of allogenic bone marrow transplantation in a patient with mucopolysaccharidosis IVA.

    PubMed

    Chinen, Yasutsugu; Higa, Takeshi; Tomatsu, Shunji; Suzuki, Yasuyuki; Orii, Tadao; Hyakuna, Nobuyuki

    Mucopolysaccharidosis IVA (MPS IVA) is one of the lysosomal storage diseases. It is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of the specific glycosaminoglycans keratan sulfate and chondroitin-6-sulfate. This accumulation has a direct impact on cartilage and bone development, resulting in systemic skeletal dysplasia. There is no curative therapy for this skeletal dysplasia. This report describes long-term therapeutic efficacy in a 15-year-old boy with a severe form of MPS IVA who received successful allogeneic bone marrow transplantation (BMT) from his HLA-identical carrier sister. The level of the GALNS enzyme in the recipient's lymphocytes reached almost half of normal level within two years after BMT. For the successive 9+ years post-BMT, GALNS activity in his lymphocytes maintained the same level as the donor's, and the level of urinary uronic acid was reduced. Lumbar bone mineral density increased around 50% one year later post-BMT and was kept consistent. Radiographs showed that the figures of trochanter major and minor appeared, while the epiphyseal dysplasia in the femoral cap was almost unchanged. Loud snoring and apnea disappeared. Vital capacity increased to around 20% for the first two years and was maintained. Activity of daily life (ADL) was improved in work/study efficacy, respiratory status, sleep, joint pain, and frequency of infection. In conclusion, the long-term study of hematopoetic stem cell transplantation has shown clinical improvements in respiratory function, radiograph findings, ADL, and biochemical findings, suggesting that it is a potential therapeutic option for patients with MPS IVA.

  4. Occipitocervical stabilization using bilateral laminar C2 screws in children with mucopolysaccharidosis IVA.

    PubMed

    Vanek, Petr; Homolkova, Helena; Benes, Vladimir; Zeman, Jiri

    2015-12-01

    Mucopolysaccharidosis IVA (MPS IVA) is a multisystemic storage disorder. Patient's disability and life expectancy depends upon skeletal complications, including cervical myelopathy due to upper cervical compression or instability. Posterior decompression followed by occipitocervical fixation or C1-2 fusion are the most frequently recommended surgical interventions. The bony elements of C1 and C2 are often inadequately developed making routine screw insertion difficult. The main purpose of this work was to present novel technique of occipitocervical fixation using two C2 laminar screws. Four children with MPS IVA underwent decompression and C0-C2 instrumented fusion using two C2 bilateral laminar screws. The dimensions of the C2 lamina were measured. Clinical and radiological results were monitored prospectively for a minimum 3 years. The mean laminar length was 24 ± 1.15 mm, width 6.15 ± 0.55 mm and height 7.4 ± 0.6 mm. Patients remained in a stable neurological condition. The mean antero-posterior diameter of the spinal canal on the pre-operative MR was 6.2 ± 0.74 mm and it was enlarged to 11.4 ± 0.8 mm after 3 years. All screws were placed adequately. In all patients, the control CT scan 2 years post-operatively revealed a stable position of the treated segments, but solid bony fusion was not registered in any patient. Decompression and fusion of the upper cervical spine is a generally accepted approach to treat upper cervical spine instability and myelopathy in MPS IVA patients. The feasibility and the suitability of the technique of C0-C2 stabilization using bilateral C2 laminar screws have been presented.

  5. Long-term Outcome after Radiotherapy for FIGO Stage IIIB and IVA Carcinoma of the Cervix

    SciTech Connect

    Yeung, Anamaria R.; Amdur, Robert J. . E-mail: amdurrj@shands.ufl.edu; Morris, Christopher G.; Morgan, Linda S.; Mendenhall, William M.

    2007-04-01

    Purpose: To report the long-term outcome after radiotherapy with curative intent for Stage IIIB and IVA carcinoma of the cervix. Methods and Materials: We retrospectively reviewed 91 patients treated with radiotherapy with curative intent at University of Florida between January 1980 and December 2003 for Stage IIIB (84 patients) or IVA (7 patients) carcinoma of the cervix. Results: The median follow-up of the surviving patients was 8.8 years. The 5- and 10-year estimates of local control, regional control, locoregional control, relapse-free survival, and overall survival were 53% and 53%, 55% and 47%, 34% and 29%, 30% and 26%, and 29% and 21%, respectively. Ninety percent of the recurrences occurred within 2 years of treatment. Of these, 60% of all failures were local, 29% were regional, and 11% were distant failures alone. Also, 17% of the failures were in the paraaortic nodes with no evidence of failure in the pelvis. Univariate and multivariate analyses were conducted with the endpoint of relapse-free or overall survival. No factor was statistically significant. Complications from therapy were scored using the Radiation Therapy Oncology Group grading system; the overall severe late complication rate was 13% (Grade 3-5). Conclusion: This series is one of the most mature of published reports. With long-term follow-up, approximately one-third of patients with Stage IIIB or IVA carcinoma of the cervix were cured, with a 13% complication rate.

  6. Interplay of the Serine/Threonine-Kinase StkP and the Paralogs DivIVA and GpsB in Pneumococcal Cell Elongation and Division

    PubMed Central

    Campo, Nathalie; Cluzel, Caroline; Lavergne, Jean-Pierre; Freton, Céline; Combet, Christophe; Guiral, Sébastien; Soufi, Boumediene; Macek, Boris; Kuru, Erkin; VanNieuwenhze, Michael S.; Brun, Yves V.; Di Guilmi, Anne-Marie; Claverys, Jean-Pierre; Galinier, Anne; Grangeasse, Christophe

    2014-01-01

    Despite years of intensive research, much remains to be discovered to understand the regulatory networks coordinating bacterial cell growth and division. The mechanisms by which Streptococcus pneumoniae achieves its characteristic ellipsoid-cell shape remain largely unknown. In this study, we analyzed the interplay of the cell division paralogs DivIVA and GpsB with the ser/thr kinase StkP. We observed that the deletion of divIVA hindered cell elongation and resulted in cell shortening and rounding. By contrast, the absence of GpsB resulted in hampered cell division and triggered cell elongation. Remarkably, ΔgpsB elongated cells exhibited a helical FtsZ pattern instead of a Z-ring, accompanied by helical patterns for DivIVA and peptidoglycan synthesis. Strikingly, divIVA deletion suppressed the elongated phenotype of ΔgpsB cells. These data suggest that DivIVA promotes cell elongation and that GpsB counteracts it. Analysis of protein-protein interactions revealed that GpsB and DivIVA do not interact with FtsZ but with the cell division protein EzrA, which itself interacts with FtsZ. In addition, GpsB interacts directly with DivIVA. These results are consistent with DivIVA and GpsB acting as a molecular switch to orchestrate peripheral and septal PG synthesis and connecting them with the Z-ring via EzrA. The cellular co-localization of the transpeptidases PBP2x and PBP2b as well as the lipid-flippases FtsW and RodA in ΔgpsB cells further suggest the existence of a single large PG assembly complex. Finally, we show that GpsB is required for septal localization and kinase activity of StkP, and therefore for StkP-dependent phosphorylation of DivIVA. Altogether, we propose that the StkP/DivIVA/GpsB triad finely tunes the two modes of peptidoglycan (peripheral and septal) synthesis responsible for the pneumococcal ellipsoid cell shape. PMID:24722178

  7. Interplay of the serine/threonine-kinase StkP and the paralogs DivIVA and GpsB in pneumococcal cell elongation and division.

    PubMed

    Fleurie, Aurore; Manuse, Sylvie; Zhao, Chao; Campo, Nathalie; Cluzel, Caroline; Lavergne, Jean-Pierre; Freton, Céline; Combet, Christophe; Guiral, Sébastien; Soufi, Boumediene; Macek, Boris; Kuru, Erkin; VanNieuwenhze, Michael S; Brun, Yves V; Di Guilmi, Anne-Marie; Claverys, Jean-Pierre; Galinier, Anne; Grangeasse, Christophe

    2014-04-01

    Despite years of intensive research, much remains to be discovered to understand the regulatory networks coordinating bacterial cell growth and division. The mechanisms by which Streptococcus pneumoniae achieves its characteristic ellipsoid-cell shape remain largely unknown. In this study, we analyzed the interplay of the cell division paralogs DivIVA and GpsB with the ser/thr kinase StkP. We observed that the deletion of divIVA hindered cell elongation and resulted in cell shortening and rounding. By contrast, the absence of GpsB resulted in hampered cell division and triggered cell elongation. Remarkably, ΔgpsB elongated cells exhibited a helical FtsZ pattern instead of a Z-ring, accompanied by helical patterns for DivIVA and peptidoglycan synthesis. Strikingly, divIVA deletion suppressed the elongated phenotype of ΔgpsB cells. These data suggest that DivIVA promotes cell elongation and that GpsB counteracts it. Analysis of protein-protein interactions revealed that GpsB and DivIVA do not interact with FtsZ but with the cell division protein EzrA, which itself interacts with FtsZ. In addition, GpsB interacts directly with DivIVA. These results are consistent with DivIVA and GpsB acting as a molecular switch to orchestrate peripheral and septal PG synthesis and connecting them with the Z-ring via EzrA. The cellular co-localization of the transpeptidases PBP2x and PBP2b as well as the lipid-flippases FtsW and RodA in ΔgpsB cells further suggest the existence of a single large PG assembly complex. Finally, we show that GpsB is required for septal localization and kinase activity of StkP, and therefore for StkP-dependent phosphorylation of DivIVA. Altogether, we propose that the StkP/DivIVA/GpsB triad finely tunes the two modes of peptidoglycan (peripheral and septal) synthesis responsible for the pneumococcal ellipsoid cell shape.

  8. Re-Os Study of Magmatic Iron Meteorites with Low GA Abundances--Groups IVA and IVB

    NASA Astrophysics Data System (ADS)

    Smoliar, M. I.; Walker, R. J.

    1995-09-01

    IVB meteorites. The samples show a limited variation in 187Re/188Os - from 0.3231 (Cape of Good Hope) to 0.3994 (Warburton Range). Consequently, they define an isochron with comparatively low precision: slope=0.07921+/-105; age=4.58+/-0.06 Ga (relative to the IIA and IIIA ages reported previously [1]); initial 187Os/188Os=0.09530+/-37 (MSWD=1.9). The age and initial are unresolvable from isochrons for IIA and IIIA groups[1]. These IVB irons cover the entire range of Ir concentrations in this group, so the limited variation in Re/Os likely reflects the maximum range in IVB, and additional whole-rock data will not likely improve isochron precision. IVA meteorites. Seven IVA irons define an isochron with: slope=0.07721+/-46; age=4.467+/-0.027 Ga; initial 187Os/188Os=0.09584+/-41 (MSWD=1.6). The age is distinctly younger than the ages of the IIA and IIIA groups[1]. Scott et al.[2] show that the parent IVA body probably experienced a catastrophic impact soon after formation, potentially complicating the interpretation of isotopic data. The concentrations of Re and Os, however, are consistent with fractional crystallization, and are quite distinct from possible mixing lines. This likely indicates that that Re-Os systematics were produced via crystal-liquid processes and not by the mixing of native metal with metal from a projectile. The IVA isochron, along with IIA and IIIA isochrons, defines an Os isotope evolution line with slope corresponding to a Re/Os of 0.42, which is identical within error limits to that of H-chondrites. This also argues in favor of an interpretation of the IVA result as a crystallization age. Three additional IVA samples, however, deviate significantly from the isochron - La Grange (+7 sigma), Bushman Land (+7 sigma), and Duel Hill (+15 sigma). According to Scott et al.[2], the latter meteorite does not fit to their IVA crystallization model in most elemental plots. The pronounced deviation in Re-Os system may imply that Duel Hill (1854) does not

  9. Entire hemithorax irradiation for Masaoka stage IVa thymomas.

    PubMed

    Soares, André; Louro, Luís Vasco; Almeida, Marta; Sousa, Olga

    2012-01-01

    Thymomas are rare neoplasms that have an indolent growth with a preferentially intra-thoracic dissemination pattern. Surgery is currently the standard treatment of thymomas; however radiotherapy is often used in an adjuvant setting due to a high sensitivity of these tumors to such treatment. Postoperative entire hemithoracic irradiation has been used in selected Masaoka stage IVa cases after complete surgical excision of metastatic lesions. In the present article, the authors report three cases of Masaoka stage IVa thymoma that underwent entire hemithorax irradiation after surgical excision of metastatic lesions. The first two patients presented as stage IVa thymomas. The third case consisted of a pleural recurrence of a thymoma. Hemithoracic irradiation with low doses has been used by different authors; the available data shows that it is a well-tolerated treatment that could potentially lead to better loco-regional control and increased overall survival.

  10. Heart and Cardiovascular Involvement in Patients with Mucopolysaccharidosis Type IVA (Morquio-A Syndrome)

    PubMed Central

    Kampmann, Christoph; Abu-Tair, Tariq; Gökce, Seyfullah; Lampe, Christina; Reinke, Jörg; Mengel, Eugen; Hennermann, Julia B.; Wiethoff, Christiane M.

    2016-01-01

    Background Mucopolysaccharidosis (MPS) IVA is a rare lysosomal storage disorder with multiple skeletal and non-skeletal abnormalities requiring multiple surgical interventions. It is well known that patients with MPS IVA suffer from tachycardia, but cardiac and hemodynamic alterations have not been reported to date. We investigated the cardiovascular and hemodynamic alterations in patients with MPS IVA and developed a possible patho-mechanism for cardiovascular deterioration during anesthesia. Material and Methods In this observational study, serial cardiac examinations were performed in 54 patients with MPS IVA who were followed at the Children’s Hospital of the Mainz Medical University (Mainz, Germany) between 1991 and 2014 (follow-up 1–24 years; median 5.8 years). Results were compared with data from a large central European cohort of more than 2000 healthy infants and children. Results None of the patients had arterial hypertension, but 4% had evidence of increased pulmonary artery pressure. Patients developed aortic root extension up to 6.9 standard deviations above normal. Left-sided valve leaflet thickening occurred in 26 patients (five with valve disease). Patients had lower left ventricular dimensions (z: –1.02±0.1), lower stroke volumes (z: –2.3±0.17), lower left ventricular mass (z: –1.5±0.21), but higher wall thickness (z: +0.8±0.16), and higher work index (z: +2.5±0.2) compared to healthy control subjects. Cardiac output was preserved by an increase in heart rate of 21%. Sixty % of patients showed impaired diastolic filling; heart rate (99.0±1.8 vs. 92.0±2.1 bpm), age (18.0±1.8 vs. 14.2±1 years), and cardiothoracic ratio (61.6±3.6% vs. 55±4.2%) of these patients were higher compared to those with normal filling. Conclusions The results of this study suggest an age-progressive disproportion of the intra-thoracic organs of patients with MPS IVA, which is accompanied by aortic root extension and thickened left ventricles, with reduced

  11. Capturing subject variability in fMRI data: A graph-theoretical analysis of GICA vs. IVA.

    PubMed

    Laney, Jonathan; Westlake, Kelly P; Ma, Sai; Woytowicz, Elizabeth; Calhoun, Vince D; Adalı, Tülay

    2015-05-30

    Recent studies using simulated functional magnetic resonance imaging (fMRI) data show that independent vector analysis (IVA) is a superior solution for capturing spatial subject variability when compared with the widely used group independent component analysis (GICA). Retaining such variability is of fundamental importance for identifying spatially localized group differences in intrinsic brain networks. Few studies on capturing subject variability and order selection have evaluated real fMRI data. Comparison of multivariate components generated by multiple algorithms is not straightforward. The main difficulties are finding concise methods to extract meaningful features and comparing multiple components despite lack of a ground truth. In this paper, we present a graph-theoretical (GT) approach to effectively compare the ability of multiple multivariate algorithms to capture subject variability for real fMRI data for effective group comparisons. The GT approach is applied to components generated from fMRI data, collected from individuals with stroke, before and after a rehabilitation intervention. IVA is compared with widely used GICA for the purpose of group discrimination in terms of GT features. In addition, masks are applied for motor related components generated by both algorithms. Results show that IVA better captures subject variability producing more activated voxels and generating components with less mutual information in the spatial domain than Group ICA. IVA-generated components result in smaller p-values and clearer trends in GT features. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Heart and Cardiovascular Involvement in Patients with Mucopolysaccharidosis Type IVA (Morquio-A Syndrome).

    PubMed

    Kampmann, Christoph; Abu-Tair, Tariq; Gökce, Seyfullah; Lampe, Christina; Reinke, Jörg; Mengel, Eugen; Hennermann, Julia B; Wiethoff, Christiane M

    2016-01-01

    Mucopolysaccharidosis (MPS) IVA is a rare lysosomal storage disorder with multiple skeletal and non-skeletal abnormalities requiring multiple surgical interventions. It is well known that patients with MPS IVA suffer from tachycardia, but cardiac and hemodynamic alterations have not been reported to date. We investigated the cardiovascular and hemodynamic alterations in patients with MPS IVA and developed a possible patho-mechanism for cardiovascular deterioration during anesthesia. In this observational study, serial cardiac examinations were performed in 54 patients with MPS IVA who were followed at the Children's Hospital of the Mainz Medical University (Mainz, Germany) between 1991 and 2014 (follow-up 1-24 years; median 5.8 years). Results were compared with data from a large central European cohort of more than 2000 healthy infants and children. None of the patients had arterial hypertension, but 4% had evidence of increased pulmonary artery pressure. Patients developed aortic root extension up to 6.9 standard deviations above normal. Left-sided valve leaflet thickening occurred in 26 patients (five with valve disease). Patients had lower left ventricular dimensions (z: -1.02±0.1), lower stroke volumes (z: -2.3±0.17), lower left ventricular mass (z: -1.5±0.21), but higher wall thickness (z: +0.8±0.16), and higher work index (z: +2.5±0.2) compared to healthy control subjects. Cardiac output was preserved by an increase in heart rate of 21%. Sixty % of patients showed impaired diastolic filling; heart rate (99.0±1.8 vs. 92.0±2.1 bpm), age (18.0±1.8 vs. 14.2±1 years), and cardiothoracic ratio (61.6±3.6% vs. 55±4.2%) of these patients were higher compared to those with normal filling. The results of this study suggest an age-progressive disproportion of the intra-thoracic organs of patients with MPS IVA, which is accompanied by aortic root extension and thickened left ventricles, with reduced stroke volumes, impaired diastolic filling patterns, and

  13. Siderophile elements in IVA irons and the compaction of their parent asteroidal core

    NASA Astrophysics Data System (ADS)

    Albarède, Francis; Bouchet, Romain A.; Blichert-Toft, Janne

    2013-01-01

    The highly siderophile element concentrations of IVA irons constitute an excellent benchmark for asteroidal core processes and, so far, the paradigm, based on the negative correlation between Ni contents and crystallographic cooling rates, has been that they represent a suite of cumulates crystallizing inwards from a molten asteroidal core. It has, however, been recognized that fractional crystallization does not account for all of the siderophile concentration patterns. Here we use the experimental parameterization of siderophile element fractionation with respect to the sulfur content of molten iron (Chabot and Jones, 2003), least-squares techniques, and Monte Carlo error propagation to assess whether incremental changes in the series of IVA irons can be accounted for by fractional crystallization or rather by partial melting. We show that the apparent order of incompatibility during solid-melt segregation deduced from binary plots of siderophile elements is misleading as a result of the strong dependency of partition coefficients on the sulfur content of the melt. All models of fractional crystallization of an Fe-S melt corrected for this effect result in negative sulfur contents. The effect of interstitial melt on fractionation hence is negligible because the high sulfur content of the melts makes all the elements compatible. In contrast, residues left by the compaction of a molten asteroidal core that crystallized with traces of sulfides and silicates according to the incremental form of batch melting provide a successful representation of the IVA suite for a large number of elements. Misfit for some elements may be due to the presence of carbon or reflects memory of variations acquired during the crystallization of the core. It is likely that melting was triggered by 26Al and that melt extraction was enhanced by the high strain-rate of impacts. The calculated S content of the liquid reproduces the experimental value of the Fe-S eutectic (45% S). Inward

  14. Novel missense mutation in the GALNS gene in an affected patient with severe form of mucopolysaccharidosis type IVA.

    PubMed

    Seyedhassani, Seyed Mohammad; Hashemi-Gorji, Feyzollah; Yavari, Mahdieh; Mirfakhraie, Reza

    2015-10-23

    Mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A, is an autosomal recessive disorder characterized by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which causes major skeletal and connective tissue abnormalities and affects multiple organ systems. In this study, one MPS IVA patient with a severe form from consanguine large Iranian family has been investigated. To find a mutation, all of the 14 exons and intron-exon junctions of GALNS gene were sequenced. Sequencing results were analyzed using bioinformatic analysis in order to predict probable pathogenic effect of the variant. One novel homozygous missense mutation in exon 5, c.542A>G (p.Y181C), was found in the proband. That was predicted as being probably pathogenic by bioinformatics analysis. Segregation and familial study confirmed this pathogenic mutation. In conclusion, we have identified the novel mutation responsible for MPS IVA in an Iranian patient to assist in the diagnosis, genetic counseling and prenatal diagnosis of the affected families. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Laser photolysis and thermolysis of organic selenides and tellurides for chemical gas-phase deposition of nanostructured materials.

    PubMed

    Pola, Josef; Ouchi, Akihiko

    2009-03-12

    Laser radiation-induced decomposition of gaseous organic selenides and tellurides resulting in chemical deposition of nanostructured materials on cold surfaces is reviewed with regard to the mechanism of the gas-phase decomposition and properties of the deposited materials. The laser photolysis and laser thermolysis of the Se and Te precursors leading to chalcogen deposition can also serve as a useful approach to nanostructured chalcogen composites and IVA group (Si, Ge, Sn) element chalcogenides provided that it is carried out simultaneously with laser photolysis or thermolysis of polymer and IVA group element precursor.

  16. Recent results from DAMA/LIBRA-phase1 and perspectives

    NASA Astrophysics Data System (ADS)

    Bernabei, R.; Belli, P.; Cappella, F.; Caracciolo, V.; Cerulli, R.; Dai, C. J.; d'Angelo, A.; d'Angelo, S.; Di Marco, A.; He, H. L.; Incicchitti, A.; Kuang, H. H.; Ma, X. H.; Montecchia, F.; Sheng, X. D.; Wang, R. G.; Ye, Z. P.

    2016-04-01

    The DAMA/LIBRA experiment, consisting of about 250 kg of highly radio-pure NaI(Tl) target, is running deep underground at the Gran Sasso National Laboratory (LNGS) of the I.N.F.N.; its main aim is the investigation of Dark Matter (DM) particles in the Galactic halo by means of the model independent DM annual modulation signature. In this paper we briefly summarize the results obtained in its first phase of measurements (DAMA/LIBRA-phase1) lasted for 7 annual cycles with a total exposure of 1.04 ton ×yr. The DAMA/LIBRA-phase1 and the former DAMA/NaI data (cumulative exposure 1.33 ton ×yr, corresponding to 14 annual cycles) give evidence at 9.3 σ C.L. for the presence of DM particles in the galactic halo. No systematic or side reaction able to mimic the exploited DM signature has been found or suggested by anyone over more than a decade. At fall 2010 a relevant upgrade of the experiment has been performed: all the PMTs have been replaced by new ones having higher quantum efficiency. After some optimization periods, a new phase of measurement, DAMA/LIBRA-phase2, has began in this new configuration with increased sensitivity. Some of the perspectives of the presently running DAMA/LIBRA-phase2 are mentioned.

  17. Practical and reliable enzyme test for the detection of mucopolysaccharidosis IVA (Morquio Syndrome type A) in dried blood samples.

    PubMed

    Camelier, Marli V; Burin, Maira G; De Mari, Jurema; Vieira, Taiane A; Marasca, Giórgia; Giugliani, Roberto

    2011-09-18

    Mucopolysaccharidosis IVA (MPS IVA), or Morquio Syndrome type A, is an autosomal recessive disease caused by deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS), resulting in excessive lysosomal storage of keratan sulfate in many tissues and organs. This accumulation causes a severe skeletal dysplasia with short stature, and affects the eye, heart and other organs, with many signs and symptoms. Morquio A syndrome is estimated to occur in 1 in 200,000 to 300,000 live births. Clinical trials with enzyme replacement therapy for this disease are in progress, and it is probable that the treatment, when available, would be more effective if started early. We describe an innovative fluorometric method for the assay of GALNS in dried blood spots (DBS). We used dried blood spots (DBS) as the enzyme source and compared it with leukocytes samples, having studied 25 MPS IVA patients and 54 healthy controls. We optimized the assay conditions, including incubation time and stability of DBS samples. To eppendorf type tubes containing a 3-mm diameter blood spot we added elution liquid and substrate solution. After 2 different incubations at 37°C, the amount of hydrolyzed product was compared with a calibrator to allow the quantification of the enzyme activity. Results in DBS were compared to the ones obtained in leukocytes using the standard technique. The fluorescent methodology was validated in our laboratory and the assay was found sensitive and specific, allowing reliable detection of MPS IVA patients. The use of DBS simplifies the collection and transport steps, and is especially useful for testing patients from more remote areas of large countries, and when samples need to cross country borders. This assay could be easily incorporated into the protocol of reference laboratories and play a role in the screening for MPS IVA, contributing to earlier detection of affected patients. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Novel oral taxane therapies: recent Phase I results

    PubMed Central

    Flores, John Paul; Saif, M Wasif

    2015-01-01

    The oral taxanes are analogues of existing taxanes with a possible broad range of antitumor activity. They also have the potential advantages of ease of administration, better efficacy and lesser toxicity than currently available taxanes. These drugs have been used in several Phase I clinical trials, the methodology and results of which will be reviewed here. PMID:26146540

  19. Np Behavior in Synthesized Uranyl Phases: Results of Initial Tests

    SciTech Connect

    Friese, Judah I.; Douglas, Matthew; McNamara, Bruce K.; Clark, Sue B.; Hanson, Brady D.

    2004-09-28

    Initial tests were completed at Pacific Northwest National Laboratory for developing a potential mechanism to retard the mobility of neptunium at the Yucca Mountain repository. Neptunium is of concern because of its mobility in the environment and long half life, contributing a large percentage of the potential dose over extended times at the perimeter of the site. The mobility of neptunium could be retarded by associating with uranium mineral phases. The following four uranium mineral phases were examined and are potential secondary phases expected to form as a result of interactions of spent nuclear fuel with the local environment: meta-schoepite, studtite, uranophane, and sodium boltwoodite. The fate of the neptunium was examined in these synthetic experiments.

  20. BWR Full Integral Simulation Test (FIST). Phase I test results

    SciTech Connect

    Hwang, W S; Alamgir, M; Sutherland, W A

    1984-09-01

    A new full height BWR system simulator has been built under the Full-Integral-Simulation-Test (FIST) program to investigate the system responses to various transients. The test program consists of two test phases. This report provides a summary, discussions, highlights and conclusions of the FIST Phase I tests. Eight matrix tests were conducted in the FIST Phase I. These tests have investigated the large break, small break and steamline break LOCA's, as well as natural circulation and power transients. Results and governing phenomena of each test have been evaluated and discussed in detail in this report. One of the FIST program objectives is to assess the TRAC code by comparisons with test data. Two pretest predictions made with TRACB02 are presented and compared with test data in this report.

  1. Antidiabetic Effects of Aqueous Infusions of Artemisia herba-alba and Ajuga iva in Alloxan-Induced Diabetic Rats.

    PubMed

    Boudjelal, Amel; Siracusa, Laura; Henchiri, Cherifa; Sarri, Madani; Abderrahim, Benkhaled; Baali, Faiza; Ruberto, Giuseppe

    2015-06-01

    The aqueous infusions of the aerial parts of Artemisia herba-alba Asso and Ajuga iva Schreber, prepared in accordance with the traditional procedure used in the local folk medicine, have been analysed for their composition and content of phytochemical constituents and examined for their antidiabetic effectiveness in alloxan-induced diabetic rats. Oral administration of A. herba-alba and A. iva infusions was studied in normal and alloxan-induced diabetic rats, which were randomly divided into nine groups, each group consisting of six animals. The drug preparations (100, 200, and 300 mg/kg b. w.) of each plant were given orally to the rats of each group twice daily for 15 days. Compositional analysis of the aqueous infusions revealed the presence of several polyphenols as main components. A. herba-alba infusion was characterised by mono- and di-cinnamoylquinic acids, with 5-caffeoylquinic (chlorogenic) acid being the main compound, followed by 3,5-dicaffeoylquinic acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant among flavonoids. On the other hand, A. iva showed the exclusive presence of flavonoids, with the flavanone naringin present in relatively high levels together with several apigenin (flavone) derivatives. Oral administration of 300 mg/kg b. w. of the aqueous infusions of A. herba-alba and A. iva exhibited a significant reduction in blood glucose content, showing a much more efficient antidiabetic activity compared to glibenclamide, the oral hypoglycaemic agent used as a positive control in this study. These results suggest that A. herba-alba and A. iva possess significant antidiabetic activity, as they were able to improve the biochemical damage in alloxan-induced diabetes in rats. Georg Thieme Verlag KG Stuttgart · New York.

  2. Pilot Overmyer completes hygiene activities / demostrates IVA foot restraint

    NASA Image and Video Library

    1982-11-16

    STS005-06-230 (11-16 Nov. 1982) --- On middeck, astronaut Robert F. Overmyer, STS-5 pilot, drying his face with a towel from forward single tray personal item stowage locker, completes personal hygiene activities (shaving) and demonstrates use of intravehicular activity (IVA) foot restraint on floor. Photo credit: NASA

  3. Chikusetsusaponin IVa methyl ester induces cell cycle arrest by the inhibition of nuclear translocation of β-catenin in HCT116 cells.

    PubMed

    Lee, Kyung-Mi; Yun, Ji Ho; Lee, Dong Hwa; Park, Young Gyun; Son, Kun Ho; Nho, Chu Won; Kim, Yeong Shik

    2015-04-17

    We demonstrate that chikusetsusaponin IVa methyl ester (CME), a triterpenoid saponin from the root of Achyranthes japonica, has an anticancer activity. We investigate its molecular mechanism in depth in HCT116 cells. CME reduces the amount of β-catenin in nucleus and inhibits the binding of β-catenin to specific DNA sequences (TCF binding elements, TBE) in target gene promoters. Thus, CME appears to decrease the expression of cell cycle regulatory proteins such as Cyclin D1, as a representative target for β-catenin, as well as CDK2 and CDK4. As a result of the decrease of the cell cycle regulatory proteins, CME inhibits cell proliferation by arresting the cell cycle at the G0/G1 phase. Therefore, we suggest that CME as a novel Wnt/β-catenin inhibitor can be a putative agent for the treatment of colorectal cancers. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Preliminary time-phased TWRS process model results

    SciTech Connect

    Orme, R.M.

    1995-03-24

    This report documents the first phase of efforts to model the retrieval and processing of Hanford tank waste within the constraints of an assumed tank farm configuration. This time-phased approach simulates a first try at a retrieval sequence, the batching of waste through retrieval facilities, the batching of retrieved waste through enhanced sludge washing, the batching of liquids through pretreatment and low-level waste (LLW) vitrification, and the batching of pretreated solids through high-level waste (HLW) vitrification. The results reflect the outcome of an assumed retrieval sequence that has not been tailored with respect to accepted measures of performance. The batch data, composition variability, and final waste volume projects in this report should be regarded as tentative. Nevertheless, the results provide interesting insights into time-phased processing of the tank waste. Inspection of the composition variability, for example, suggests modifications to the retrieval sequence that will further improve the uniformity of feed to the vitrification facilities. This model will be a valuable tool for evaluating suggested retrieval sequences and establishing a time-phased processing baseline. An official recommendation on tank retrieval sequence will be made in September, 1995.

  5. First Results of the Phase II SIMPLE Dark Matter Search

    NASA Astrophysics Data System (ADS)

    Felizardo, M.; Morlat, T.; Fernandes, A. C.; Girard, T. A.; Marques, J. G.; Ramos, A. R.; Auguste, M.; Boyer, D.; Cavaillou, A.; Sudre, C.; Poupeney, J.; Payne, R. F.; Miley, H. S.; Puibasset, J.

    2010-11-01

    We report results of a 14.1kgd measurement with 15 superheated droplet detectors of total active mass 0.208 kg, comprising the first stage of a 30kgd Phase II experiment. In combination with the results of the neutron-spin sensitive XENON10 experiment, these results yield a limit of |ap|<0.32 for MW=50GeV/c2 on the spin-dependent sector of weakly interacting massive particle-nucleus interactions with a 50% reduction in the previously allowed region of the phase space, formerly defined by XENON, KIMS, and PICASSO. In the spin-independent sector, a limit of 2.3×10-5pb at MW=45GeV/c2 is obtained.

  6. First Results of the Phase II SIMPLE Dark Matter Search

    SciTech Connect

    Felizardo, M.; Morlat, T.; Girard, T. A.; Fernandes, A. C.; Marques, J. G.; Ramos, A. R.; Auguste, M.; Boyer, D.; Cavaillou, A.; Sudre, C.; Poupeney, J.; Payne, R. F.; Miley, H. S.; Puibasset, J.

    2010-11-19

    We report results of a 14.1 kg d measurement with 15 superheated droplet detectors of total active mass 0.208 kg, comprising the first stage of a 30 kg d Phase II experiment. In combination with the results of the neutron-spin sensitive XENON10 experiment, these results yield a limit of |a{sub p}|<0.32 for M{sub W}=50 GeV/c{sup 2} on the spin-dependent sector of weakly interacting massive particle-nucleus interactions with a 50% reduction in the previously allowed region of the phase space, formerly defined by XENON, KIMS, and PICASSO. In the spin-independent sector, a limit of 2.3x10{sup -5} pb at M{sub W}=45 GeV/c{sup 2} is obtained.

  7. Changes in antioxidant defense status in hypercholesterolemic rats treated with Ajuga iva.

    PubMed

    Bouderbala, S; Lamri-Senhadji, M; Prost, J; Lacaille-Dubois, M A; Bouchenak, M

    2008-06-01

    The aim of the study was to investigate the effect of aqueous extract of Ajuga iva (Ai) on serum and tissues lipid peroxidation as well as antioxidant enzymes activities in red blood cells (RBC) and tissues, in high hypercholesterolemic rats (HC). Male Wistar rats (n=12) were fed on 1% cholesterol-enriched diet for 15d. After this adaptation phase, hypercholesterolemic rats (total cholesterol=6.5+/-0.6mol/l) were divided into two groups fed the same diet and treated or not with Ai for 15d. Thiobarbituric acid reactive substances (TBARS) concentrations in serum, LDL-HDL(1), HDL(2) and HDL(3) were respectively, 5-, 7.8-, 2.3- and 5-fold lower in Ai treated than untreated hypercholesterolemic groups. TBARS concentrations were 1.4-fold lower in heart and 2.8-fold higher in kidney in Ai-HC treated than untreated HC group. Superoxide dismutase activity was respectively, 1.2- and 1.4-fold higher in RBC and muscle in Ai treated than untreated group. In RBC, Ajuga iva treatment enhanced glutathione peroxidase (GSH-Px) (+9%) and glutathione reductase (GSSH-Red) (+12%) in Ai-HC treated than untreated HC group. GSSH-Red activity was 1.4- and 1.5-fold higher in adipose tissue and heart, respectively and 3.7-fold lower in kidney in Ai treated than untreated group. Liver catalase activity was 1.6-fold higher in Ai treated than untreated group. Adipose tissue and muscle total glutathione content represented in Ai treated group 35% and 36% of the value noted in untreated group. Nitric oxide values of liver, adipose tissue and heart were 3.3-, 2.5- and 3.4-fold higher in Ai-HC than HC group. Ajuga iva treatment enhanced alpha-tocopherol contents (+25%) in Ai treated than untreated group. In conclusion, Ajuga iva treatment is more effective to improve the antioxidant capacity of RBC than that of tissues. Indeed, Ai is able to reduce the oxidative stress in hypercholesterolemic rats by increasing the antioxidant enzymes activity.

  8. Er:YAG clinical results on hard tissue: phase II

    NASA Astrophysics Data System (ADS)

    Cozean, Colette D.; Powell, G. L.

    1998-04-01

    Objective: In Phase I, we demonstrated the safety and efficacy of the pulsed 2.94 micron Er:YAG laser for caries removal, cavity preparation and laser etching utilizing in vivo teeth scheduled for removal to quantitatively verify the safety of the product for up to one year following treatment. Phase II was a continuation of this study evaluating in vivo teeth to verify the safety and efficacy of the Er:YAG in a long-term follow-up study. Methods: We randomly divided the patients into two groups: a laser group and a control group, which employed the high speed drill. The investigators rated clinical efficacy by several criteria, evaluated pain and measured pulpal vitality up to two years following treatment. This phase consisted of 512 procedures that made up the laser group and 357 procedures that made up the control group. Conclusions: The results from this phase showed that the Er:YAG laser was able to perform as well as, if not better than, the drill in caries removal, cavity preparation, and acid etching alone. Use of the laser virtually eliminated the need for anesthesia. The Er:YAG laser is safe and efficacious for removal of caries, cavity preparation and etching prior to acid etching.

  9. omega-Aga IVA selectively inhibits the calcium-dependent fraction of the evoked release of [3H]GABA from synaptosomes.

    PubMed

    Sitges, M; Chiu, L M

    1995-09-01

    The effect of omega-Aga IVA, a P-type Ca2+ channel blocker, on the release of the inhibitory neurotransmitter GABA and on the elevation of Cai induced by depolarization was investigated in [3H]GABA and fura-2 preloaded mouse brain synaptosomes, respectively. Two strategies (i.e. 20 mM external K+ and veratridine) that depolarize by different mechanisms the preparation were used. High K+ elevates Cai and induces [3H]GABA release in the absence of external Na+ and in the presence of TTX, conditions that abolish veratridine induced responses. The effect of omega-Aga IVA on the Ca2+ and Na+ dependent fractions of the depolarization evoked release of [3H]GABA were separately investigated in synaptosomes depolarized with high K+ in the absence of external Na+ and with veratridine in the absence of external Ca2+, respectively. The Ca2+ dependent fraction of the evoked release of [3H]GABA and the elevation of Ca2+ induced by high K+ are markedly inhibited (about 50%) in synaptosomes exposed to omega-Aga IVA (300 nM) for 3 min before depolarization, whereas the Na+ dependent, Ca2+ independent carrier mediated release of [3H]GABA induced by veratridine, which is sensitive to verapamil and amiloride, is not modified by omega-Aga IVA. Our results indicate that an omega-Aga IVA sensitive type of Ca2+ channel is highly involved in GABA exocytosis.

  10. Analytical results for a three-phase traffic model.

    PubMed

    Huang, Ding-wei

    2003-10-01

    We study analytically a cellular automaton model, which is able to present three different traffic phases on a homogeneous highway. The characteristics displayed in the fundamental diagram can be well discerned by analyzing the evolution of density configurations. Analytical expressions for the traffic flow and shock speed are obtained. The synchronized flow in the intermediate-density region is the result of aggressive driving scheme and determined mainly by the stochastic noise.

  11. Results from the Sudbury Neutrino Observatory Phase III

    SciTech Connect

    SNO Collaboration; Prior, G.

    2008-11-03

    The third and last phase of the Sudbury Neutrino Observatory (SNO) used a technique independent of previous methods, to measure the rate of neutral-current interactions in heavy water and determine precisely the total active {sup 8}B solar neutrino flux. The total flux obtained is 5.54{sub -0.31}{sup +0.33}(stat){sub -0.34}{sup +0.36}(syst) x 10{sup 6} cm{sup -2}s{sup -1}, in agreement with previous measurements and standard solar models. Results from a global analysis of solar and reactor neutrino give {Delta}m{sup 2} = 7.59{sub -0.21}{sup +0.19} x 10{sup -5} eV{sup 2} and {theta} = 34.4{sub -1.2}{sup +1.3} degrees with a reduced uncertainty on the mixing angle compared to previous phases.

  12. Dense nonaqueous phase liquid tracer tests: experimental results.

    PubMed

    Burt, R A; Christians, G L; Williams, S P; Wilson, D J

    2001-12-01

    Two dense nonaqueous phase liquid (DNAPL) tracer tests were carried out in a shallow aquifer north of Fort Worth, TX. i-Propanol was used as the nonpartitioning tracer: n-hexanol and n-octanol were the partitioning tracers. Field data, mathematical modeling, the results of column tests, and field tracer tests with NaCl were used in designing the DNAPL tracer tests. The results indicated the presence of DNAPL at both sites tested; semi-quantitative estimates of the amounts of DNAPL present were obtained by mathematical modeling. Interpretation was complicated by heterogeneity of the aquifer and mass transport effects.

  13. Characterization of divIVA and other genes located in the chromosomal region downstream of the dcw cluster in Streptococcus pneumoniae.

    PubMed

    Fadda, Daniela; Pischedda, Carla; Caldara, Fabrizio; Whalen, Michael B; Anderluzzi, Daniela; Domenici, Enrico; Massidda, Orietta

    2003-10-01

    We analyzed the chromosome region of Streptococcus pneumoniae located downstream of the division and cell wall (dcw) cluster that contains the homolog of the Bacillus subtilis cell division gene divIVA and some genes of unknown function. Inactivation of divIVA in S. pneumoniae resulted in severe growth inhibition and defects in cell shape, nucleoid segregation, and cell division. Inactivation of the ylm genes resulted in some morphological and/or division abnormalities, depending on the inactivated gene. Transcriptional analysis revealed a relationship between these genes and the ftsA and ftsZ cell division genes, also indicating that the connection between the dcw cluster and the divIVA region is more extensive than just chromosomal position and gene organization.

  14. DAMA/LIBRA-phase1 results and perspectives of the phase2

    NASA Astrophysics Data System (ADS)

    Bernabei, R.; Belli, P.; Cappella, F.; Caracciolo, V.; Cerulli, R.; Dai, C. J.; d'Angelo, A.; d'Angelo, S.; Di Marco, A.; He, H. L.; Incicchitti, A.; Kuang, H. H.; Ma, X. H.; Montecchia, F.; Sheng, X. D.; Wang, R. G.; Ye, Z. P.

    2016-07-01

    The DAMA/LIBRA experiment (˜ 250 kg of highly radio-pure NaI(Tl)) is running deep underground at the Gran Sasso National Laboratory (LNGS) of the I.N.F.N. Here we briefly recall the results obtained in its first phase of measurements (DAMA/LIBRA-phase1; total exposure: 1.04 ton × yr). DAMA/LIBRA-phase1 and the former DAMA/NaI (cumulative exposure: 1.33 ton × yr) give evidence at 9.3 σ C.L. for the presence of DM particles in the galactic halo by exploiting the model-independent DM annual modulation signature. No systematic or side reaction able to mimic the exploited DM signature has been found or suggested by anyone over more than a decade. At present DAMA/LIBRA-phase2 is running with increased sensitivity.

  15. A fracture mechanics study of the phase separating planar electrodes: Phase field modeling and analytical results

    NASA Astrophysics Data System (ADS)

    Haftbaradaran, H.; Maddahian, A.; Mossaiby, F.

    2017-05-01

    It is well known that phase separation could severely intensify mechanical degradation and expedite capacity fading in lithium-ion battery electrodes during electrochemical cycling. Experiments have frequently revealed that such degradation effects could be substantially mitigated via reducing the electrode feature size to the nanoscale. The purpose of this work is to present a fracture mechanics study of the phase separating planar electrodes. To this end, a phase field model is utilized to predict how phase separation affects evolution of the solute distribution and stress profile in a planar electrode. Behavior of the preexisting flaws in the electrode in response to the diffusion induced stresses is then examined via computing the time dependent stress intensity factor arising at the tip of flaws during both the insertion and extraction half-cycles. Further, adopting a sharp-interphase approximation of the system, a critical electrode thickness is derived below which the phase separating electrode becomes flaw tolerant. Numerical results of the phase field model are also compared against analytical predictions of the sharp-interphase model. The results are further discussed with reference to the available experiments in the literature. Finally, some of the limitations of the model are cautioned.

  16. Investigation of group IVA elements combined with HAXPES and first-principles calculations

    NASA Astrophysics Data System (ADS)

    Cui, Y.-T.; Li, G.-L.; Oji, H.; Son, J.-Y.

    2014-04-01

    The core level and valence band spectra of group IVA elements were investigated with hard x-ray photoemission spectroscopy (HAXPES) photon energy of 7.939 keV by bulk sensitive manner. The survey and valance band spectra were presented, relative peaks intensity are discussed by thinking about inelastic mean free path (IMFP) and photoionization cross section of photoelectrons (PICS). In order to understand bulk band structures, valence bands are compared with the calculated ones by considering PICS, IMFP and total energy resolution. The calculated results by GGA, HSE06 and GW0 methods are simply discussed by comparing with experiment spectra.

  17. Comparison of IVA and GIG-ICA in Brain Functional Network Estimation Using fMRI Data

    PubMed Central

    Du, Yuhui; Lin, Dongdong; Yu, Qingbao; Sui, Jing; Chen, Jiayu; Rachakonda, Srinivas; Adali, Tulay; Calhoun, Vince D.

    2017-01-01

    Spatial group independent component analysis (GICA) methods decompose multiple-subject functional magnetic resonance imaging (fMRI) data into a linear mixture of spatially independent components (ICs), some of which are subsequently characterized as brain functional networks. Group information guided independent component analysis (GIG-ICA) as a variant of GICA has been proposed to improve the accuracy of the subject-specific ICs estimation by optimizing their independence. Independent vector analysis (IVA) is another method which optimizes the independence among each subject's components and the dependence among corresponding components of different subjects. Both methods are promising in neuroimaging study and showed a better performance than the traditional GICA. However, the difference between IVA and GIG-ICA has not been well studied. A detailed comparison between them is demanded to provide guidance for functional network analyses. In this work, we employed multiple simulations to evaluate the performances of the two approaches in estimating subject-specific components and time courses under conditions of different data quality and quantity, varied number of sources generated and inaccurate number of components used in computation, as well as the presence of spatially subject-unique sources. We also compared the two methods using healthy subjects' test-retest resting-state fMRI data in terms of spatial functional networks and functional network connectivity (FNC). Results from simulations support that GIG-ICA showed better recovery accuracy of both components and time courses than IVA for those subject-common sources, and IVA outperformed GIG-ICA in component and time course estimation for the subject-unique sources. Results from real fMRI data suggest that GIG-ICA resulted in more reliable spatial functional networks and yielded higher and more robust modularity property of FNC, compared to IVA. Taken together, GIG-ICA is appropriate for estimating networks

  18. Fe2+-Mg order-disorder study in orthopyroxenes from São João Nepomuceno (IVA) iron meteorite

    NASA Astrophysics Data System (ADS)

    dos Santos, E.; Scorzelli, R. B.; Varela, M. E.; Munayco, P.

    2014-01-01

    São João Nepomuceno (SJN) is an iron meteorite belonging to IVA chemical group. It consists of Fe-Ni metal matrix and silicate inclusions made of a coarse-grained mixture of tridymite, orthopyroxene and clinopyroxene. In spite of the extensive work performed on the IVA group there is still no consensus about their origin and its thermal history is subject of ongoing debates. In this work, we report preliminary results on Fe2 + distribution in the non-equivalent octahedral sites in orthopyroxene crystals extracted from São João Nepomuceno in order to infer on the thermal history of this meteorite and therefore acquire more information related to the origin of the IVA iron meteorite group.

  19. Analysis of SBIR phase I and phase II review results at the National Institutes of Health.

    PubMed

    Vener, K J; Calkins, B M

    1991-09-01

    A cohort of phase I and phase II summary statements for the SBIR grant applications was evaluated to determine the strengths and weaknesses in approved and disapproved applications. An analysis of outcome variables (disapproval or unfunded status) was examined with respect to exposure variables (strengths or shortcomings). Logistic regression models were developed for comparisons to measure the predictive value of shortcomings and strengths to the outcomes. Disapproved phase I results were compared with an earlier 1985 study. Although the magnitude of the frequencies of shortcomings was greater in the present study, the relative rankings within shortcoming class were more alike than different. Also, the frequencies of shortcomings were, with one exception, not significantly different in the two studies. Differences in the summary statement review may have accounted for some differences observed between the 1985 data and results of the present study. Comparisons of Approved/Disapproved and Approved-Unfunded/Funded yielded the following observations. For phase I applicants, a lack of a clearly stated, testable hypothesis, a poorly qualified or described investigative team, and inadequate methodological approaches contributed significantly (in that order) to a rating of disapproval. A critical flaw for phase II proposals was failure to accomplish objectives of the phase I study. Methodological issues also dominate the distinctions in both comparison groups. A clear result of the data presented here and that published previously is that SBIR applicants need continuing assistance to improve the chances of their success. These results should serve as a guide to assist NIH staff as they provide information to prospective applicants focusing on key elements of the application. A continuing review of the SBIR program would be helpful to evaluate the quality of the submitted science.

  20. EXPERIMENTAL RESULTS OF THE NEPHELINE PHASE III STUDY

    SciTech Connect

    Fox, K.; Edwards, T.

    2009-11-09

    This study is the third phase in a series of experiments designed to reduce conservatism in the model that predicts the formation of nepheline, a crystalline phase that can reduce the durability of high level waste glass. A Phase I study developed a series of glass compositions that were very durable while their nepheline discriminator values were well below the current nepheline discriminator limit of 0.62, where nepheline is predicted to crystallize upon slow cooling. A Phase II study selected glass compositions to identify any linear effects of composition on nepheline crystallization and that were restricted to regions that fell within the validation ranges of the Defense Waste Processing Facility (DWPF) Product Composition Control System (PCCS) models. However, it was not possible to identify any linear effects of composition on chemical durability performance for this set of study glasses. The results of the Phase II study alone were not sufficient to recommend modification of the current nepheline discriminator. It was recommended that the next series of experiments continue to focus not only on compositional regions where the PCCS models are considered applicable (i.e., the model validation ranges), but also be restricted to compositional regions where the only constraint limiting processing is the current nepheline discriminator. Two methods were used in selecting glasses for this Phase III nepheline study. The first was based on the relationship of the current nepheline discriminator model to the other DWPF PCCS models, and the second was based on theory of crystallization in mineral and glass melts. A series of 29 test glass compositions was selected for this study using a combination of the two approaches. The glasses were fabricated and characterized in the laboratory. After reviewing the data, the study glasses generally met the target compositions with little issue. Product Consistency Test results correlated well with the crystallization analyses in

  1. Linear inductive voltage adders (IVA) for advanced hydrodynamic radiography

    SciTech Connect

    Mazarakis, M.G.; Boyes, J.D.; Johnson, D.L.

    1998-09-01

    The electron beam which drifts through the multiple cavities of conventional induction linacs (LIA) is replaced in an IVA by a cylindrical metal conductor which extends along the entire length of the device and effectuates the addition of the accelerator cavity voltages. In the approach to radiography, the linear inductive voltage adder drives a magnetically immersed electron diode with a millimeter diameter cathode electrode and a planar anode/bremsstrahlung converter. Both anode and cathode electrodes are immersed in a strong (15--50 T) solenoidal magnetic field. The electron beam cross section is approximately of the same size as the cathode needle and generates a similar size, very intense x-ray beam when it strikes the anode converter. An IVA driven diode can produce electron beams of equal size and energy as a LIA but with much higher currents (40--50 kA versus 4--5 kA), simpler hardware and thus lower cost. The authors present here first experimental validations of the technology utilizing HERMES 3 and SABRE IVA accelerators. The electron beam voltage and current were respectively of the order of 10 MV and 40 kA. X-ray doses of up to 1 kR {at} 1 m and spot sizes as small as 1.7 mm (at 200 R doses) were measured.

  2. Surgical Approaches for Stage IVA Thymic Epithelial Tumors

    PubMed Central

    Shapiro, Mark; Korst, Robert J.

    2014-01-01

    Thymic epithelial tumors (TET) are rare mediastinal neoplasms that can metastasize to the pleural space (stage IVA). Complete surgical resection remains the backbone of therapy for patients with early stage TET, however, the role of surgery in the management of patients with stage IVA disease is not fully defined. Published reports in this regard are mainly small, retrospective, and uncontrolled, with unclear inclusion criteria. Surgical options to manage pleural disease include metastasectomy, extrapleural pneumonectomy, and metastasectomy/pleurectomy combined with heated intrapleural chemotherapy. The choice of the most appropriate surgical strategy needs to be individualized according to the quantity and location of disease, the patient’s overall condition, as well as operator and institutional expertise. In the majority of cases, metastasectomy of pleural implants will be sufficient to achieve a complete resection. The available literature suggests that in selected patients with stage IVA TET, delivery of neoadjuvant chemotherapy followed by complete resection is a viable treatment option that can be associated with long-term survival. PMID:24459636

  3. Surgical Approaches for Stage IVA Thymic Epithelial Tumors.

    PubMed

    Shapiro, Mark; Korst, Robert J

    2014-01-14

    Thymic epithelial tumors (TET) are rare mediastinal neoplasms that can metastasize to the pleural space (stage IVA). Complete surgical resection remains the backbone of therapy for patients with early stage TET, however, the role of surgery in the management of patients with stage IVA disease is not fully defined. Published reports in this regard are mainly small, retrospective, and uncontrolled, with unclear inclusion criteria. Surgical options to manage pleural disease include metastasectomy, extrapleural pneumonectomy, and metastasectomy/pleurectomy combined with heated intrapleural chemotherapy. The choice of the most appropriate surgical strategy needs to be individualized according to the quantity and location of disease, the patient's overall condition, as well as operator and institutional expertise. In the majority of cases, metastasectomy of pleural implants will be sufficient to achieve a complete resection. The available literature suggests that in selected patients with stage IVA TET, delivery of neoadjuvant chemotherapy followed by complete resection is a viable treatment option that can be associated with long-term survival.

  4. Intellectual and neurological functioning in Morquio syndrome (MPS IVa).

    PubMed

    Davison, J E; Kearney, S; Horton, J; Foster, K; Peet, A C; Hendriksz, C J

    2013-03-01

    Mucopolysaccharidosis type IVa (MPS IVa, Morquio syndrome OMIM #253000) is a lysosomal storage disease caused by deficiency in N-acetylgalactosamine-6-sulfatase (GALNS, EC 3.1.6.4; encoded by GALNS gene at 16q24.3). Unlike other MPS disorders involving excessive heparan and dermatan sulfate, Morquio syndrome has not been associated with neurological involvement nor with intellectual impairment as this disorder of keratan sulfate has been described as a purely visceral and skeletal disorder. Neurocognitive assessment was undertaken of MPS IVa patients with age appropriate intellectual tests as well as a Child Behaviour Checklist as part of clinical follow up. Available neuroimaging studies (MRI and MR spectroscopy) were reviewed. Whilst more than half of the overall IQ scores fell in the average range, scores for 3/8 children fell below average. A number of behavioural problems were highlighted, including anxiety/depression, attention and somatic complaints. Subtle neuroimaging abnormalities were demonstrated in over half of the children. These findings present a challenge to existing assumptions about the nature of Morquio A syndrome. A hypothesis regarding the potential role of calcium signalling is explored.

  5. DAMA/LIBRA-phase1 model independent results

    NASA Astrophysics Data System (ADS)

    Bernabei, R.; Belli, P.; D'Angelo, S.; di Marco, A.; Montecchia, F.; D'Angelo, A.; Incicchitti, A.; Prosperi, D.; Cappella, F.; Caracciolo, V.; Cerulli, R.; Dai, C. J.; He, H. L.; Kuang, H. H.; Ma, X. H.; Sheng, X. D.; Wang, R. G.; Ye, Z. P.

    2016-10-01

    Experimental observations and theoretical arguments at Galaxy and larger scales have suggested that a large fraction of the Universe is composed by Dark Matter (DM) particles. This has motivated the DAMA experimental efforts to investigate the presence of such particles in the galactic halo by exploiting a model independent signature with highly radiopure setups deep underground. In this paper, a review of the results obtained with the total exposure of 1.04 ton × yr collected by DAMA/LIBRA-phase1 deep underground at the Gran Sasso National Laboratory (LNGS) of the INFN during seven annual cycles is given. The DAMA/LIBRA-phase1 data give evidence for the presence of DM particles in the galactic halo, on the basis of the exploited model independent DM annual modulation signature by using highly radiopure NaI(Tl) target, at 7.5σ C.L. Including also the data of the first generation DAMA/NaI experiment (cumulative exposure 1.33 ton × yr, corresponding to 14 annual cycles), the C.L. is 9.3σ and the modulation amplitude of the single-hit scintillation events in the (2-6) keV energy interval is: (0.0112 ± 0.0012) cpd/kg/keV; the measured phase is (144 ± 7) days and the measured period is (0.998 ± 0.002) yr, values well in agreement with those expected for DM particles. No systematic or side reaction able to mimic the exploited DM signature has been found or suggested by anyone over more than a decade.

  6. Results from phase I of the GERDA experiment

    SciTech Connect

    Wester, Thomas

    2015-10-28

    The GERmanium Detector Array Gerda at the Laboratori Nazionali del Gran Sasso of the INFN in Italy is an experiment dedicated to the search for the neutrinoless double beta (0νββ) decay in {sup 76}Ge. The experiment employs high purity germanium detectors enriched in {sup 76}Ge inside a 64 m{sup 3} cryostat filled with liquid argon. Gerda was planned in two phases of data taking with the goal to reach a half-life sensitivity in the order of 10{sup 26} yr. Phase I of Gerda was running from November 2011 until May 2013. With about 18 kg total detector mass, data with an exposure of 21.6 kg·yr was collected and a background index of 0.01 cts/(keV·kg·yr) was achieved in the region of interest. No signal was found for the 0νββ decay and a new limit of T{sub 1/2} > 2.1 · 10{sup 25} yr (90% C.L.) was obtained, strongly disfavoring the previous claim of observation. Furthermore, the 2νββ decay half-life of {sup 76}Ge was measured with unprecedented precision. Other results include new half-life limits of the order of 10{sup 23} yr for Majoron emitting double beta decay modes with spectral indices n = 1, 2, 3, 7 and new limits in the order of 10{sup 23} yr for 2νββ decays to the first 3 excited states of {sup 76}Se. In Phase II, currently in preparation, the detector mass will be doubled while reducing the background index by a factor of 10.

  7. Results of Phase 3 of the CATIE Schizophrenia Trial

    PubMed Central

    Stroup, T. Scott; Lieberman, Jeffrey A.; McEvoy, Joseph P.; Davis, Sonia M.; Swartz, Marvin S.; Keefe, Richard S.E.; Miller, Alexander L.; Rosenheck, Robert A.; Hsiao, John K.

    2009-01-01

    Objective The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study examined the comparative effectiveness of antipsychotic treatments for individuals with chronic schizophrenia. Patients who had discontinued antipsychotic treatment in phases 1 and 2 were eligible for phase 3, in which they selected one of nine antipsychotic regimens with the help of their study doctor. We describe the characteristics of the patients who selected each treatment option and their outcomes. Method Two hundred and seventy patients entered phase 3. The open-label treatment options were monotherapy with oral aripiprazole, clozapine, olanzapine, perphenazine, quetiapine, risperidone, ziprasidone, long-acting injectable fluphenazine decanoate, or a combination of any two of these treatments. Results Few patients selected fluphenazine decanoate (n=9) or perphenazine (n=4). Similar numbers selected each of the other options (range 33–41). Of the seven common choices, those who selected clozapine and combination antipsychotic treatment were the most symptomatic, and those who selected aripiprazole and ziprasidone had the highest body mass index. Symptoms improved for all groups, although the improvements were modest for the groups starting with relatively mild levels of symptoms. Side effect profiles of the medications varied considerably but medication discontinuations due to intolerability were rare (7% overall). Conclusions Patients and their doctors made treatment selections based on clinical factors, including severity of symptoms, response to prior treatments, and physical health status. Fluphenazine decanoate was rarely used among those with evidence of treatment non-adherence and clozapine was underutilized for those with poor previous response. Combination antipsychotic treatment warrants further study. PMID:19027269

  8. Adenoviral L4 33K forms ring-like oligomers and stimulates ATPase activity of IVa2: implications in viral genome packaging

    PubMed Central

    Ahi, Yadvinder S.; Vemula, Sai V.; Hassan, Ahmed O.; Costakes, Greg; Stauffacher, Cynthia; Mittal, Suresh K.

    2015-01-01

    The mechanism of genome packaging in adenoviruses (AdVs) is presumed to be similar to that of dsDNA viruses including herpesviruses and dsDNA phages. First, the empty capsids are assembled after which the viral genome is pushed through a unique vertex by a motor which consists of three minimal components: an ATPase, a small terminase and a portal. Various components of this motor exist as ring-like structures forming a central channel through which the DNA travels during packaging. In AdV, the IVa2 protein is believed to function as a packaging ATPase, however, the equivalents of the small terminase and the portal have not been identified in AdVs. IVa2 interacts with another viral protein late region 4 (L4) 33K which is important for genome packaging. Both IVa2 and 33K are expressed at high levels during the late stage of virus infection. The oligomeric state of IVa2 and 33K was analyzed in virus-infected cells, IVa2 and 33K transfected cells, AdV particles, or as recombinant purified proteins. Electron microscopy of the purified proteins showed ring-like oligomers for both proteins which is consistent with their putative roles as a part of the packaging motor. We found that the ATPase activity of IVa2 is stimulated in the presence of 33K and the AdV genome. Our results suggest that the 33K functions analogous to the small terminase proteins and so will be part of the packaging motor complex. PMID:25954255

  9. Difference in agr Dysfunction and Reduced Vancomycin Susceptibility between MRSA Bacteremia Involving SCCmec Types IV/IVa and I–III

    PubMed Central

    Choi, Su-Mi; Park, Kyung-Hwa; Shin, Jong-Hee; Choy, Hyon E.; Jung, Sook-In; Kim, Hong Bin

    2012-01-01

    Background Dysfunction of agr, with reduced susceptibility or hetero-resistance to vancomycin, is thought to be associated with a worse outcome of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (MRSAB). However, the difference in agr dysfunction according to the SCCmec type in MRSA infection is undetermined. We compared the prevalence of agr dysfunction, reduced vancomycin susceptibility and the outcomes of SCCmec IV/IVa and I–III MRSAB. Methods The study included 307 cases of MRSAB. SCCmec types were determined by multiplex PCR. The clinical and microbiological features and outcomes of 58 SCCmec IV/IVa MRSAB were compared with those of 249 SCCmec I–III MRSAB. Results Compared with SCCmec I–III MRSAB, SCCmec IV/IVa MRSAB was associated with lower rates of agr dysfunction (3% vs. 43%), vancomycin minimum inhibitory concentration (MIC) = 2 µg/mL (3% vs. 15%), and hetero-resistance to vancomycin (0% vs. 8%) (all P<0.05). However, the 30-day and S. aureus-related mortality in patients with SCCmec IV/IVa MRSAB were not different from those in patients with SCCmec I–III MRSAB in multivariate analyses (HR 1.168, 95% CI 0.705–1.938; HR 1.025, 95% CI 0.556–1.889). Conclusions SCCmec IV/IVa MRSAB was associated with lower rates of agr dysfunction and hetero-resistance to vancomycin and a lower vancomycin MIC, compared with SCCmec I–III MRSAB. However, the outcomes of SCCmec IV/IVa MRSAB did not differ from those of SCCmec I–III MRSAB. PMID:23152862

  10. Cryogenic Two-Phase Flight Experiment: Results overview

    NASA Technical Reports Server (NTRS)

    Swanson, T.; Buchko, M.; Brennan, P.; Bello, M.; Stoyanof, M.

    1995-01-01

    This paper focuses on the flight results of the Cryogenic Two-Phase Flight Experiment (CRYOTP), which was a Hitchhiker based experiment that flew on the space shuttle Columbia in March of 1994 (STS-62). CRYOTP tested two new technologies for advanced cryogenic thermal control; the Space Heat Pipe (SHP), which was a constant conductance cryogenic heat pipe, and the Brilliant Eyes Thermal Storage Unit (BETSU), which was a cryogenic phase-change thermal storage device. These two devices were tested independently during the mission. Analysis of the flight data indicated that the SHP was unable to start in either of two attempts, for reasons related to the fluid charge, parasitic heat leaks, and cryocooler capacity. The BETSU test article was successfully operated with more than 250 hours of on-orbit testing including several cooldown cycles and 56 freeze/thaw cycles. Some degradation was observed with the five tactical cryocoolers used as thermal sinks, and one of the cryocoolers failed completely after 331 hours of operation. Post-flight analysis indicated that this problem was most likely due to failure of an electrical controller internal to the unit.

  11. DAMA/LIBRA-phase1 results and perspectives of the phase2

    NASA Astrophysics Data System (ADS)

    Bernabei, R.; Belli, P.; Cappella, F.; Caracciolo, V.; Cerulli, R.; Dai, C. J.; d'Angelo, A.; d'Angelo, S.; Di Marco, A.; He, H. L.; Incicchitti, A.; Kuang, H. H.; Ma, X. H.; Montecchia, F.; Sheng, X. D.; Wang, R. G.; Ye, Z. P.

    2015-05-01

    The results obtained with the total exposure of 1.04 ton × yr collected by DAMA/LIBRA-phase1 deep underground at the Gran Sasso National Laboratory (LNGS) of the I.N.F.N. during 7 annual cycles are summarized. The DAMA/LIBRA-phase1 and the former DAMA/NaI data (cumulative exposure 1.33 ton × yr, corresponding to 14 annual cycles) give evidence at 9.3 σ C.L. for the presence of Dark Matter (DM) particles in the galactic halo, on the basis of the exploited model independent DM annual modulation signature by using highly radio-pure NaI(Tl) target. No systematic or side reaction able to mimic the exploited DM signature has been found or suggested by anyone over more than a decade. The same data of DAMA/LIBRA-phase1 have also been analyzed searching for possible DM second-order diurnal effect; at present, the DM diurnal modulation amplitude - expected because of the Earth diurnal motion - evaluated on the basis of the DAMA Dark Matter annual modulation results is below the reached experimental sensitivity. Some of the perspectives of the presently running DAMA/LIBRA-phase2 are outlined.

  12. Detection of Actinobacillus pleuropneumoniae in pigs by real-time quantitative PCR for the apxIVA gene.

    PubMed

    Tobias, T J; Bouma, A; Klinkenberg, D; Daemen, A J J M; Stegeman, J A; Wagenaar, J A; Duim, B

    2012-08-01

    A real-time quantitative PCR (qPCR) for detection of the apxIVA gene of Actinobacillus pleuropneumoniae was validated using pure cultures of A. pleuropneumoniae and tonsillar and nasal swabs from experimentally inoculated Caesarean-derived/colostrum-deprived piglets and naturally infected conventional pigs. The analytical sensitivity was 5colony forming units/reaction. In comparison with selective bacterial examination using tonsillar samples from inoculated animals, the diagnostic sensitivity of the qPCR was 0.98 and the diagnostic specificity was 1.0. The qPCR showed consistent results in repeatedly sampled conventional pigs. Tonsillar brush samples and apxIVA qPCR analysis may be useful for further epidemiological studies and monitoring for A. pleuropneumoniae. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Multi-Path Transportation Futures Study. Results from Phase 1

    SciTech Connect

    Phil Patterson, Phil; Singh, Margaret; Plotkin, Steve; Moore, Jim

    2007-03-09

    Presentation reporting Phase 1 results, 3/9/2007. Projecting the future role of advanced drivetrains and fuels in the light vehicle market is inherently difficult, given the uncertainty (and likely volatility) of future oil prices, inadequate understanding of likely consumer response to new technologies, the relative infancy of several important new technologies with inevitable future changes in their performance and costs, and the importance — and uncertainty — of future government marketplace interventions (e.g., new regulatory standards or vehicle purchase incentives). The Multi-Path Transportation Futures (MP) Study has attempted to improve our understanding of this future role by examining several scenarios of vehicle costs, fuel prices, government subsidies, and other key factors. These are projections, not forecasts, in that they try to answer a series of “what if” questions without assigning probabilities to most of the basic assumptions.

  14. The Continual Intercomparison of Radiation Codes: Results from Phase I

    NASA Technical Reports Server (NTRS)

    Oreopoulos, Lazaros; Mlawer, Eli; Delamere, Jennifer; Shippert, Timothy; Cole, Jason; Iacono, Michael; Jin, Zhonghai; Li, Jiangnan; Manners, James; Raisanen, Petri; hide

    2011-01-01

    The computer codes that calculate the energy budget of solar and thermal radiation in Global Climate Models (GCMs), our most advanced tools for predicting climate change, have to be computationally efficient in order to not impose undue computational burden to climate simulations. By using approximations to gain execution speed, these codes sacrifice accuracy compared to more accurate, but also much slower, alternatives. International efforts to evaluate the approximate schemes have taken place in the past, but they have suffered from the drawback that the accurate standards were not validated themselves for performance. The manuscript summarizes the main results of the first phase of an effort called "Continual Intercomparison of Radiation Codes" (CIRC) where the cases chosen to evaluate the approximate models are based on observations and where we have ensured that the accurate models perform well when compared to solar and thermal radiation measurements. The effort is endorsed by international organizations such as the GEWEX Radiation Panel and the International Radiation Commission and has a dedicated website (i.e., http://circ.gsfc.nasa.gov) where interested scientists can freely download data and obtain more information about the effort's modus operandi and objectives. In a paper published in the March 2010 issue of the Bulletin of the American Meteorological Society only a brief overview of CIRC was provided with some sample results. In this paper the analysis of submissions of 11 solar and 13 thermal infrared codes relative to accurate reference calculations obtained by so-called "line-by-line" radiation codes is much more detailed. We demonstrate that, while performance of the approximate codes continues to improve, significant issues still remain to be addressed for satisfactory performance within GCMs. We hope that by identifying and quantifying shortcomings, the paper will help establish performance standards to objectively assess radiation code quality

  15. Group IVA phospholipase A2 participates in the progression of hepatic fibrosis.

    PubMed

    Ishihara, Keiichi; Miyazaki, Akira; Nabe, Takeshi; Fushimi, Hideaki; Iriyama, Nao; Kanai, Shiho; Sato, Takashi; Uozumi, Naonori; Shimizu, Takao; Akiba, Satoshi

    2012-10-01

    Group IVA phospholipase A2 (IVA-PLA2) is an enzyme that intiates the arachidonic acid pathway and plays an important role in inflammation. We demonstrate that IVA-PLA2 deficiency suppresses lipid deposition in the liver, which was induced by administration of a high-fat and -cholesterol diet (HFCD) for 16 wk in mice. Herein, we performed 2-dimensional gel-based comparative proteomics to further define the suppressive effect of IVA-PLA2 deficiency on fatty liver formation. In comparisons among 4 groups, wild-type (WT)/normal diet (ND), IVA-PLA2-deficient knockout (KO)/ND, WT/HFCD, and KO/HFCD, 4 proteins, 3 of which are associated with hepatic fibrosis, were identified as molecules, of which altered expression by HFCD was suppressed in KO mice compared to WT mice. Therefore, we assessed the effect of IVA-PLA2 deficiency on hepatic fibrosis induced by HFCD or carbon tetrachloride (CCl4) in mouse models. Biochemical and histological analyses revealed that IVA-PLA2 deficiency markedly reduced overall collagen accumulation in the liver of HFCD- and CCl4-derived mouse models. We found that IVA-PLA2 deficiency prevented activation of hepatic stellate cells and infiltration of F4/80-positive macrophages without affecting other immunocytes such as CD8+ lymphocytes and natural killer cells. In summary, IVA-PLA2 deficiency attenuates not only lipid deposition in the liver but also hepatic fibrosis formation.

  16. ECAS Phase I fuel cell results. [Energy Conservation Alternatives Study

    NASA Technical Reports Server (NTRS)

    Warshay, M.

    1978-01-01

    This paper summarizes and discusses the fuel cell system results of Phase I of the Energy Conversion Alternatives Study (ECAS). Ten advanced electric powerplant systems for central-station baseload generation using coal were studied by NASA in ECAS. Three types of low-temperature fuel cells (solid polymer electrolyte, SPE, aqueous alkaline, and phosphoric acid) and two types of high-temperature fuel cells (molten carbonate, MC, and zirconia solid electrolyte, SE) were studied. The results indicate that (1) overall efficiency increases with fuel cell temperature, and (2) scale-up in powerplant size can produce a significant reduction in cost of electricity (COE) only when it is accompanied by utilization of waste fuel cell heat through a steam bottoming cycle and/or integration with a gasifier. For low-temperature fuel cell systems, the use of hydrogen results in the highest efficiency and lowest COE. In spite of higher efficiencies, because of higher fuel cell replacement costs integrated SE systems have higher projected COEs than do integrated MC systems. Present data indicate that life can be projected to over 30,000 hr for MC fuel cells, but data are not yet sufficient for similarly projecting SE fuel cell life expectancy.

  17. Final model independent results of DAMA/LIBRA-phase1 and perspectives of phase2

    NASA Astrophysics Data System (ADS)

    Bernabei, R.; Belli, P.; Cappella, F.; Caracciolo, V.; Castellano, S.; Cerulli, R.; Dai, C. J.; d'Angelo, A.; d'Angelo, S.; Di Marco, A.; He, H. L.; Incicchitti, A.; Kuang, H. H.; Ma, X. H.; Montecchia, F.; Prosperi, D.; Sheng, X. D.; Wang, R. G.; Ye, Z. P.

    2015-03-01

    This paper shortly summarizes the results obtained with the total exposure of 1.04 ton × yr collected by DAMA/LIBRA-phase1 deep underground at the Gran Sasso National Laboratory (LNGS) of the I.N.F.N. during 7 annual cycles. The DAMA/LIBRA-phase1 and the former DAMA/NaI data (cumulative exposure 1.33 ton × yr, corresponding to 14 annual cycles) give evidence at 9.3 σ C.L. for the presence of Dark Matter (DM) particles in the galactic halo, on the basis of the exploited model independent DM annual modulation signature by using highly radio-pure NaI(Tl) target. The modulation amplitude of the single-hit events in the (2-6) keV energy interval is: (0.0112 ± 0.0012) cpd/kg/keV; the measured phase is (144 ± 7) days and the measured period is (0.998 ± 0.002) yr, values well in agreement with those expected for DM particles. No systematic or side reaction able to mimic the exploited DM signature has been found or suggested by anyone over more than a decade. Some of the perspectives of the presently running DAMA/LIBRA-phase2 are outlined.

  18. Bicell fibre optics homodyne phase demodulator: experimental results

    NASA Astrophysics Data System (ADS)

    Holdynski, Z.; Merta, I.; Nasilowski, T.; Jaroszewicz, L. R.

    2013-05-01

    We present possibility of demodulation signals with different types of modulation. Our setup gives possibility to obtain high accuracy and precision of measurements. We explain how to optimize the setup to obtain optimum condition to phase demodulation for signals with different types of modulation. Real time phase measurements and stable working conditions are provided experimentally. Thermal stabilization and errors analysis based on geometrical and physical setup parameters is demonstrated and optimized, too. Our phase demodulation method is effective and simple in opposite to other phase decoding methods with are overloaded by digital signal processing steps.

  19. Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels.

    PubMed

    Donida, Bruna; Marchetti, Desirèe P; Jacques, Carlos Eduardo Diaz; Ribas, Graziela; Deon, Marion; Manini, Paula; da Rosa, Helen Tais; Moura, Dinara Jaqueline; Saffi, Jenifer; Giugliani, Roberto; Vargas, Carmen Regla

    2017-06-01

    Morquio A disease (Mucopolysaccharidosis type IVA, MPS IVA) is one of the 11 mucopolysaccharidoses (MPSs), a heterogeneous group of inherited lysosomal storage disorders (LSDs) caused by deficiency in enzymes need to degrade glycosaminoglycans (GAGs). Morquio A is characterized by a decrease in N-acetylgalactosamine-6-sulfatase activity and subsequent accumulation of keratan sulfate and chondroitin 6-sulfate in cells and body fluids. As the pathophysiology of this LSD is not completely understood and considering the previous results of our group concerning oxidative stress in Morquio A patients receiving enzyme replacement therapy (ERT), the aim of this study was to investigate oxidative stress parameters in Morquio A patients at diagnosis. It was studied 15 untreated Morquio A patients, compared with healthy individuals. The affected individuals presented higher lipid peroxidation, assessed by urinary 15-F2t-isoprostane levels and no protein damage, determined by sulfhydryl groups in plasma and di-tyrosine levels in urine. Furthermore, Morquio A patients showed DNA oxidative damage in both pyrimidines and purines bases, being the DNA damage positively correlated with lipid peroxidation. In relation to antioxidant defenses, affected patients presented higher levels of reduced glutathione (GSH) and increased activity of glutathione peroxidase (GPx), while superoxide dismutase (SOD) and glutathione reductase (GR) activities were similar to controls. Our findings indicate that Morquio A patients present at diagnosis redox imbalance and oxidative damage to lipids and DNA, reinforcing the idea about the importance of antioxidant therapy as adjuvant to ERT, in this disorder.

  20. Mechanical properties, anisotropy and hardness of group IVA ternary spinel nitrides

    NASA Astrophysics Data System (ADS)

    Ding, Ying-Chun; Chen, Min

    2013-10-01

    In this work, new ternary cubic spinel structures are designed by the substitutional method. The structures, elasticity properties, intrinsic hardness and Debye temperature of the cubic ternary spinel nitrides are studied by first principles based on the density-functional theory. The results show that γ-CSn2N4, γ-SiC2N4, γ-GeC2N4 and γ-SnC2N4 are not mechanically stable. The elastic constants Cij of these cubic spinel structures are obtained using the stress-strain method. Derived elastic constants, such as bulk modulus, shear modulus, Young's modulus, Poisson coefficient and brittle/ductile behaviour are estimated using Voigt-Reuss-Hill theories. The B/G value, the Poisson's ratio and anisotropic factor are calculated for eight ternary stable crystals. Based on the microscopic hardness model, we further estimate the Vickers hardness of all the stable crystals. From the calculated hardness of the stable group IVA ternary spinel nitrides by Gao's and Jiang's methods, it is observed that the stable group IVA ternary spinel nitrides are not superhard materials except for γ-CSi2N4. Furthermore, the Debye temperature for the eight stable crystals is also estimated.

  1. Hypoglycaemic effect of the lyophilised aqueous extract of Ajuga iva in normal and streptozotocin diabetic rats.

    PubMed

    El Hilaly, Jaouad; Lyoussi, Badiâa

    2002-05-01

    The purpose of this study was to examine the hypoglycaemic effect of the lyophilised aqueous extract of the whole plant of Ajuga iva (L.) Schreber (Labiatae) in normal and streptozotocin-induced diabetic rats. Single and repeated oral administration of the extract of Ajuga iva L (AI) at a dose of 10 mg/kg produced a slight and significant decrease in plasma glucose levels in normal rats 6 h after administration and after 3 weeks of treatment. AI reduced plasma glucose levels of streptozotocin diabetic rats from 337+/-9.3 to 102.2+/-17.7 mg/dl after 6 h of oral administration (P<0.001). Repeated oral administration of AI to streptozotocin diabetic rats significantly decreased the plasma glucose levels after 1 week of treatment (112+/-14.4 mg/dl at 1 week vs 337+/-9.3 mg/dl at the baseline values, (P<0.001). It continuously decreased thereafter and showed a rapid normalisation after 1 week of AI treatment. It is concluded that these results demonstrated that the water extract of the whole plant of AI possess a strong hypoglycaemic effect in diabetic rats, and support therefore, its traditional use in diabetes mellitus control.

  2. Graphite electrode arc melter demonstration Phase 2 test results

    SciTech Connect

    Soelberg, N.R.; Chambers, A.G.; Anderson, G.L.; O`Connor, W.K.; Oden, L.L.; Turner, P.C.

    1996-06-01

    Several U.S. Department of Energy organizations and the U.S. Bureau of Mines have been collaboratively conducting mixed waste treatment process demonstration testing on the near full-scale graphite electrode submerged arc melter system at the Bureau`s Albany (Oregon) Research Center. An initial test series successfully demonstrated arc melter capability for treating surrogate incinerator ash of buried mixed wastes with soil. The conceptual treatment process for that test series assumed that buried waste would be retrieved and incinerated, and that the incinerator ash would be vitrified in an arc melter. This report presents results from a recently completed second series of tests, undertaken to determine the ability of the arc melter system to stably process a wide range of {open_quotes}as-received{close_quotes} heterogeneous solid mixed wastes containing high levels of organics, representative of the wastes buried and stored at the Idaho National Engineering Laboratory (INEL). The Phase 2 demonstration test results indicate that an arc melter system is capable of directly processing these wastes and could enable elimination of an up-front incineration step in the conceptual treatment process.

  3. Aminoglycoside binding and catalysis specificity of aminoglycoside 2″-phosphotransferase IVa: A thermodynamic, structural and kinetic study

    PubMed Central

    Kaplan, Elise; Guichou, Jean-François; Chaloin, Laurent; Kunzelmann, Simone; Leban, Nadia; Serpersu, Engin H.; Lionne, Corinne

    2016-01-01

    Background Aminoglycoside O-phosphotransferases make up a large class of bacterial enzymes that is widely distributed among pathogens and confer a high resistance to several clinically used aminoglycoside antibiotics. Aminoglycoside 2″-phosphotransferase IVa, APH(2″)-IVa, is an important member of this class, but there is little information on the thermodynamics of aminoglycoside binding and on the nature of its rate-limiting step. Methods We used isothermal titration calorimetry, electrostatic potential calculations, molecular dynamics simulations and X-ray crystallography to study the interactions between the enzyme and different aminoglycosides. We determined the rate-limiting step of the reaction by the means of transient kinetic measurements. Results For the first time, Kd values were determined directly for APH(2″)-IVa and different aminoglycosides. The affinity of the enzyme seems to anti-correlate with the molecular weight of the ligand, suggesting a limited degree of freedom in the binding site. The main interactions are electrostatic bonds between the positively charged amino groups of aminoglycosides and Glu or Asp residues of APH. In spite of the significantly different ratio Kd/Km, there is no large difference in the transient kinetics obtained with the different aminoglycosides. We show that a product release step is rate-limiting for the overall reaction. Conclusions APH(2″)-IVa has a higher affinity for aminoglycosides carrying an amino group in 2′ and 6′, but tighter bindings do not correlate with higher catalytic efficiencies. As with APH(3′)-IIIa, an intermediate containing product is preponderant during the steady state. General significance This intermediate may constitute a good target for future drug design. PMID:26802312

  4. Biological activity of natural phytoecdysteroids from Ajuga iva against the sweetpotato whitefly Bemisia tabaci and the persea mite Oligonychus perseae.

    PubMed

    Aly, Radi; Ravid, Uzi; Abu-Nassar, Jackline; Botnick, Ilan; Lebedev, Galina; Gal, Shira; Ziadna, Hammam; Achdari, Guy; Smirov, Evgeny; Meir, Ayala; Ghanim, Murad

    2011-12-01

    Ecdysteroids are steroid hormones that control moulting and govern several changes during metamorphoses in arthropods. The discovery of the same molecules (phytoecdysteroids) in several plant species displayed a wide array of rather beneficial agricultural impact. Many representatives of the genus Ajuga plants contain phytoecdysteroids with a 5β-7-ene-6-one system exhibiting physiological activities in insects. By means of chromatographic (silica gel column, TLC) and LC-MS, two major ecdysteroids (20-hydroxyecdysone and cyasterone) have been isolated and identified from Israeli carpet bugle Ajuga iva (L.) Schreber (Lamiales: Lamiaceae) plants. Ajuga iva extract fractionated on the silica gel column yielded two fractions that showed high activity against the sweetpotato whitefly Bemisis tabaci and the persea mite Oligonychus perseae. A dose of 5 mg AI L(-1) of the purely identified A. iva ecdysterone significantly reduced fecundity, fertility and survival of these pests, while commercial 20-hydroxyecdysone at the same dose had lesser effects. The results demonstrate considerable efficacy of natural phytoecdysteroids against major agricultural pests, and suggests that these materials should be considered for potential development of friendly control agents. Copyright © 2011 Society of Chemical Industry.

  5. CIM5 Phase III base process development results

    SciTech Connect

    Witt, D.C.

    2000-01-06

    Integrated Demonstration Runs for the Am/Cm vitrification process were initiated in the Coupled 5-inch Cylindrical Induction Melter (CIM5) on 11/30/98 and completed on 12/9/98. Four successful runs at 60 wt% lanthanide loading were completed which met or exceeded all established criteria. The operating parameters used in these runs established the base conditions for the 5-inch Cylindrical Induction Melter (CIM5) process and were summarized in the 5-inch CIM design basis, SRT-AMC-99-OO01. (1) In subsequent tests, a total of fourteen CIM5 runs were performed using various power inputs, ramp rates and target temperatures to define the preferred processing conditions (2) Process stability and process flexibility were the key criteria used in assessing the results for each run. A preferred set of operating parameters was defined for the CIM5 batch process and these conditions were used to generate a pre-programmed, automatic processing cycle that was used for the last six CIM.5 runs (3) These operational tests were successfully completed in the January-February time frame and were summarized in SRT-AMC-99-00584. The recommended set of operating conditions defined in Runs No.1 through No.14 was used as the starting point for further pilot system runs to determine the robustness of the process, evaluate a bubbler, and investigate off-normal conditions. CIM5 Phase III Runs No.15 through No.60 were conducted utilizing the pre-programmed, automatic processing cycle to investigate system performance. This report summarizes the results of these tests and provides a recommendation for the base process as well as a processing modification for minimizing volume expansions if americium and/or curium are subject to a thermal reduction reaction like cerium. This document summarizes the results of the base process development tests conducted in the Am/Cm Pilot Facility located in Building 672-T.

  6. Technical Appendices to the National Day Care Study: Background Materials. Final Report of the National Day Care Study. Volume IV-A.

    ERIC Educational Resources Information Center

    Ruopp, Richard; And Others

    This final report of the National Day Care Study (NDCS), Volume IV-A, contains three papers that help to set a context for interpreting overall study results. "Research Issues in Day Care, A Focused Review of the Literature" focuses on effects of group care and regulatable characteristics of the day care environment. The second paper,…

  7. Status and first results of the NEMO Phase-2 tower

    NASA Astrophysics Data System (ADS)

    Chiarusi, T.; Aiello, S.; Ameli, F.; Anghinolfi, M.; Barbarino, G.; Barbarito, E.; Barbato, F.; Beverini, N.; Biagi, S.; Bouhadef, B.; Bozza, C.; Cacopardo, G.; Calamai, M.; Calì, C.; Capone, A.; Caruso, F.; Ceres, A.; Circella, M.; Cocimano, R.; Coniglione, R.; Costa, M.; Cuttone, G.; D'Amato, C.; D'Amato, V.; D'Amico, A.; DeBonis, G.; De Luca, V.; Deniskina, N.; De Rosa, G.; Distefano, C.; Fermani, P.; Flaminio, V.; Fusco, L. A.; Garufi, F.; Giordano, V.; Giovanetti, G.; Gmerk, A.; Grasso, R.; Grella, G.; Hugon, C.; Imbesi, M.; Kulikovsky, V.; Larosa, G.; Lattuada, D.; Leonora, E.; Litrico, P.; Lonardo, A.; Longhitano, F.; Lo Presti, D.; Maccioni, E.; Margiotta, A.; Martini, A.; Masullo, R.; Migliozzi, P.; Migneco, E.; Miraglia, A.; Mollo, C.; Mongelli, M.; Morganti, M.; Musico, P.; Musumeci, M.; Nicolau, C. A.; Orlando, A.; Papaleo, R.; Pellegrino, C.; Pellegriti, M. G.; Perrina, C.; Piattelli, P.; Pugliatti, C.; Pulvirenti, S.; Raffaelli, F.; Randazzo, N.; Riccobene, G.; Rovelli, A.; Sanguineti, M.; Sapienza, P.; Sgura, I.; Simeone, F.; Sipala, V.; Spurio, M.; Speziale, F.; Spitaleri, A.; Taiuti, M.; Terreni, G.; Trasatti, L.; Trovato, A.; Ventura, C.; Vicini, P.; Viola, S.; Vivolo, D.

    2014-03-01

    In March 2013, the NEMO Phase 2 tower has been successfully installed in the Capo Passero site, at a depth of 3500 m and 80 km off from the southern coast of Sicily. The unfurled tower is 450 m high; it is composed of 8 mechanical floors, for a total amount of 32 PMTs and various instruments for environmental measurements. The tower positioning is achieved by an acoustic system. The tower is continuously acquiring and transmitting all the measured signals to shore. Data reduction is completely performed in the Portopalo shore station by a dedicated computing facility connected to the persistent storage system at LNS, in Catania. Results from the last 9 months of acquisition will be presented. In particular, the analyzed optical rates, showing stable and low baseline values, are compatible with the contribution mainly of 40K light emission, with a small percentage of light bursts due to bioluminescence. These features reveal the optimal nature of the Capo Passero abyssal site to host a km3-sized Neutrino Telescope.

  8. Multi-path transportation futures study: Results from Phase 1

    SciTech Connect

    Patterson, Phil; Singh, Margaret; Plotkin, Steve; Moore, Jim

    2007-03-09

    This PowerPoint briefing provides documentation and details for Phase 1 of the Multi-Path Transportation Futures Study, which compares alternative ways to make significant reductions in oil use and carbon emissions from U.S. light vehicles to 2050. Phase I, completed in 2006, was a scoping study, aimed at identifying key analytic issues and constructing a study design. The Phase 1 analysis included an evaluation of several pathways and scenarios; however, these analyses were limited in number and scope and were designed to be preliminary.

  9. Results from the first operation phase of W7-X

    NASA Astrophysics Data System (ADS)

    Pedersen, Thomas Sunn

    2016-10-01

    This talk will give a review of stellarator physics and the mission of Wendelstein 7-X (W7-X), and will summarize the most important results obtained during its first operation phase, OP1.1, which was completed in March 2016. The HELIAS reactor vision and open issues in stellarator research will also be discussed. The stellarator concept dates back to the 1950's. It has several intrinsic advantages, including being free of current-driven disruptions, and not needing current drive. However, the stellarator has been lagging behind the tokamak with respect to energy confinement. Recent advances in plasma theory and computational power have led to renewed interest in stellarators since they allow a complex but effective optimization of the confinement properties, one that should allow for tokamak-like confinement times. W7-X is the largest and most optimized stellarator in the world, and aims to show that the earlier weaknesses of the stellarator concept have been addressed successfully by optimization, and that the intrinsic advantages of the concept persist, also at plasma parameters approaching those of a future fusion power plant. It is built for steady-state operation, featuring 70 superconducting coils, and a confinement volume of about 30 m3. During OP1.1, it was operated at full field (B = 2.5 T on axis), with ECRH power up to 4.3 MW (later to be extended to 10 MW). Plasma operation was performed with helium and hydrogen, with deuterium planned for later phases. More than 2,000 discharges were created during the 10 operation weeks of OP1.1. Core Te 8 keV and Ti 2 keV were reached in discharge with densities in the low to mid 1019 range, and confinement times were on the order of 100-150 ms, within expectation. This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement Number 633053.

  10. Integrated thermal treatment system study -- Phase 2 results. Revision 1

    SciTech Connect

    Feizollahi, F.; Quapp, W.J.

    1996-02-01

    This report presents the second phase of a study on thermal treatment technologies. The study consists of a systematic assessment of nineteen thermal treatment alternatives for the contact-handled mixed low-level waste (MLLW) currently stored in the US Department of Energy complex. The treatment alternatives consist of widely varying technologies for safely destroying the hazardous organic components, reducing the volume, and preparing for final disposal of the MLLW. The alternatives considered in Phase 2 were innovative thermal treatments with nine types of primary processing units. Other variations in the study examined the effect of combustion gas, air pollution control system design, and stabilization technology for the treatment residues. The Phase 1 study examined ten initial thermal treatment alternatives. The Phase 2 systems were evaluated in essentially the same manner as the Phase 1 systems. The alternatives evaluated were: rotary kiln, slagging kiln, plasma furnace, plasma gasification, molten salt oxidation, molten metal waste destruction, steam gasification, Joule-heated vitrification, thermal desorption and mediated electrochemical oxidation, and thermal desorption and supercritical water oxidation. The quantities, and physical and chemical compositions, of the input waste used in the Phase 2 systems differ from those in the Phase 1 systems, which were based on a preliminary waste input database developed at the onset of the Integrated Thermal Treatment System study. The inventory database used in the Phase 2 study incorporates the latest US Department of Energy information. All systems, both primary treatment systems and subsystem inputs, have now been evaluated using the same waste input (2,927 lb/hr). 28 refs., 88 figs., 41 tabs.

  11. Role of diversity in ICA and IVA: theory and applications

    NASA Astrophysics Data System (ADS)

    Adalı, Tülay

    2016-05-01

    Independent component analysis (ICA) has been the most popular approach for solving the blind source separation problem. Starting from a simple linear mixing model and the assumption of statistical independence, ICA can recover a set of linearly-mixed sources to within a scaling and permutation ambiguity. It has been successfully applied to numerous data analysis problems in areas as diverse as biomedicine, communications, finance, geo- physics, and remote sensing. ICA can be achieved using different types of diversity—statistical property—and, can be posed to simultaneously account for multiple types of diversity such as higher-order-statistics, sample dependence, non-circularity, and nonstationarity. A recent generalization of ICA, independent vector analysis (IVA), generalizes ICA to multiple data sets and adds the use of one more type of diversity, statistical dependence across the data sets, for jointly achieving independent decomposition of multiple data sets. With the addition of each new diversity type, identification of a broader class of signals become possible, and in the case of IVA, this includes sources that are independent and identically distributed Gaussians. We review the fundamentals and properties of ICA and IVA when multiple types of diversity are taken into account, and then ask the question whether diversity plays an important role in practical applications as well. Examples from various domains are presented to demonstrate that in many scenarios it might be worthwhile to jointly account for multiple statistical properties. This paper is submitted in conjunction with the talk delivered for the "Unsupervised Learning and ICA Pioneer Award" at the 2016 SPIE Conference on Sensing and Analysis Technologies for Biomedical and Cognitive Applications.

  12. Results of the Gallium-Clad Phase 3 and Phase 4 tasks (canceled prior to completion)

    SciTech Connect

    Morris, R.N.

    1998-08-01

    This report summarizes the results of the Gallium-Clad interactions Phase 3 and 4 tasks. Both tasks were to involve examining the out-of-pile stability of residual gallium in short fuel rods with an imposed thermal gradient. The thermal environment was to be created by an electrical heater in the center of the fuel rod and coolant flow on the rod outer cladding. Both tasks were canceled due to difficulties with fuel pellet fabrication, delays in the preparation of the test apparatus, and changes in the Fissile Materials Disposition program budget.

  13. MATISSE: alignment, integration, and test phase first results

    NASA Astrophysics Data System (ADS)

    Allouche, F.; Robbe-Dubois, S.; Lagarde, S.; Cruzalèbes, P.; Antonelli, P.; Bresson, Y.; Fantei-Caujolle, Y.; Marcotto, A.; Morel, S.; Beckmann, U.; Bettonvil, F.; Berio, Ph.; Heininger, M.; Lehmitz, M.; Agocs, T.; Brast, R.; Elswijk, E.; Ives, D.; Meixner, K.; Laun, W.; Mellein, M.; Neumann, U.; Bailet, C.; Clausse, J.-M.; Matter, A.; Meilland, A.; Millour, F.; Petrov, R. G.; Accardo, M.; Bristow, P.; Frahm, R.; Glindemann, A.; Gonzáles Herrera, J.-C.; Lizon, J.-L.; Schöller, M.; Graser, U.; Jaffe, W.; Lopez, B.

    2016-08-01

    between the COB and the WOP took place resulting in the first interference fringes in the L-band during summer 2015 and the first interference fringes in the N-ban in March 2016. After a period of optimization of both the instrument reliability and the environmental working conditions, the test plan is presently being conducted in order to evaluate the complete performance of the instrument and its compliance with the high-level requirements. The present paper gives the first results of the alignment, integration and test phase of the MATISSE instrument.

  14. IVA (Illinois Vocational Association) Workshops--An Innovative Approach to Inservice Education

    ERIC Educational Resources Information Center

    Anderson, Edward T.

    1974-01-01

    A joint effort in inservice education between the Illinois Division of Vocational and Technical Education and the Illinois Vocational Association (IVA) created ten diversified mini workshops which were conducted at the 1973 IVA convention in Chicago. The overall, average participant rating for the workshop was 3.76 on a one-to-four continuum. (EA)

  15. IVA (Illinois Vocational Association) Workshops--An Innovative Approach to Inservice Education

    ERIC Educational Resources Information Center

    Anderson, Edward T.

    1974-01-01

    A joint effort in inservice education between the Illinois Division of Vocational and Technical Education and the Illinois Vocational Association (IVA) created ten diversified mini workshops which were conducted at the 1973 IVA convention in Chicago. The overall, average participant rating for the workshop was 3.76 on a one-to-four continuum. (EA)

  16. Localisation of DivIVA by targeting to negatively curved membranes

    PubMed Central

    Lenarcic, Rok; Halbedel, Sven; Visser, Loek; Shaw, Michael; Wu, Ling Juan; Errington, Jeff; Marenduzzo, Davide; Hamoen, Leendert W

    2009-01-01

    DivIVA is a conserved protein in Gram-positive bacteria and involved in various processes related to cell growth, cell division and spore formation. DivIVA is specifically targeted to cell division sites and cell poles. In Bacillus subtilis, DivIVA helps to localise other proteins, such as the conserved cell division inhibitor proteins, MinC/MinD, and the chromosome segregation protein, RacA. Little is known about the mechanism that localises DivIVA. Here we show that DivIVA binds to liposomes, and that the N terminus harbours the membrane targeting sequence. The purified protein can stimulate binding of RacA to membranes. In mutants with aberrant cell shapes, DivIVA accumulates where the cell membrane is most strongly curved. On the basis of electron microscopic studies and other data, we propose that this is due to molecular bridging of the curvature by DivIVA multimers. This model may explain why DivIVA localises at cell division sites. A Monte-Carlo simulation study showed that molecular bridging can be a general mechanism for binding of proteins to negatively curved membranes. PMID:19478798

  17. Effect of aqueous extract of Ajuga iva supplementation on plasma lipid profile and tissue antioxidant status in rats fed a high-cholesterol diet.

    PubMed

    Chenni, A; Yahia, D Ait; Boukortt, F O; Prost, J; Lacaille-Dubois, M A; Bouchenak, M

    2007-01-19

    The present study was designed to explore the possible antioxidant and hypolipidemic effects of the aqueous extract of Ajuga iva (0.5% in the diet) in rats fed a high-cholesterol (1%) diet (HCD). The results indicated that the HCD-Ai versus HCD treatment led to many changes in biochemical parameters. They showed a decrease of plasma total cholesterol (TC) and VLDL-cholesterol but an increase of HDL(2)-cholesterol. The triacylglycerol contents were reduced in plasma and in VLDL. The lipid peroxidation determined by TBARS was decreased by 75% in plasma. TBARS in liver, heart and kidneys were highly reduced excepted in the adipose tissue. Ajuga iva treatment enhanced superoxide dismutase activity in liver and kidney. Glutathione reductase activity was lowered in adipose tissue but increased in liver and in kidney. A significant increase was noted in glutathione peroxidase activity in liver, heart and kidney but a low value in adipose tissue was observed. In conclusion, the present study demonstrates that in addition to its potent TG and TC-lowering effects, Ajuga iva is effective in improving the antioxidant status by reducing lipid peroxidation in plasma and tissues and enhancing the antioxidant enzymes in rats fed high-cholesterol diet. Furthermore, Ajuga iva may reduce intestinal cholesterol absorption.

  18. Two variants of staphylococcal cassette chromosome mec type IVA in community-associated meticillin-resistant Staphylococcus aureus strains in South Korea.

    PubMed

    Park, Chulmin; Shin, Hyun-Ho; Kwon, Eun-Young; Choi, Su-Mi; Kim, Si-Hyun; Park, Sun Hee; Choi, Jung-Hyun; Yoo, Jin-Hong; Lee, Dong-Gun; Shin, Wan Shik

    2009-10-01

    Meticillin-resistant Staphylococcus aureus (MRSA) strains harbouring staphylococcal cassette chromosome mec (SCCmec) type IVA are known to be more prevalent in South Korea than in other countries. Variations in the SCCmec IVA structure have been identified, including in sequence type (ST) 1 and ST72 strains. This study compared and investigated the genetic characteristics of two subtypes common in South Korea. Type IVA SCCmec of ST1 strains was characterized by type IV features with the linearized pUB110 at the junkyard (J) 3 region. However, that of ST72 strains carried a variant class B mec complex, ccrA2, with an identity of approximately 96 % and the linearized pUB110 at the J3 region. In SCCmec of ST72 strains, the organization of the class B variant and the J3 region may be more similar to that of type IA than to other types, but the ccr type and other J regions seemed to be derived from type IV. These genetic characteristics showed that type IVA appears to result from the dynamic genetic exchange and recombination of SCC DNA.

  19. Pan-PPAR agonist IVA337 is effective in experimental lung fibrosis and pulmonary hypertension.

    PubMed

    Avouac, Jerome; Konstantinova, Irena; Guignabert, Christophe; Pezet, Sonia; Sadoine, Jeremy; Guilbert, Thomas; Cauvet, Anne; Tu, Ly; Luccarini, Jean-Michel; Junien, Jean-Louis; Broqua, Pierre; Allanore, Yannick

    2017-11-01

    To evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH). IVA337 has been evaluated in the mouse model of bleomycin-induced pulmonary fibrosis and in Fra-2 transgenic mice, this latter being characterised by non-specific interstitial pneumonia and severe vascular remodelling of pulmonary arteries leading to PH. Mice received two doses of IVA337 (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. IVA337 demonstrated at a dose of 100 mg/kg a marked protection from the development of lung fibrosis in both mouse models compared with mice receiving 30 mg/kg of IVA337 or vehicle. Histological score was markedly reduced by 61% in the bleomycin model and by 50% in Fra-2 transgenic mice, and total lung hydroxyproline concentrations decreased by 28% and 48%, respectively, as compared with vehicle-treated mice. IVA337 at 100 mg/kg also significantly decreased levels of fibrogenic markers in lesional lungs of both mouse models. In addition, IVA337 substantially alleviated PH in Fra-2 transgenic mice by improving haemodynamic measurements and vascular remodelling. In primary human lung fibroblasts, IVA337 inhibited in a dose-dependent manner fibroblast to myofibroblasts transition induced by TGF-β and fibroblast proliferation mediated by PDGF. We demonstrate that treatment with 100 mg/kg IVA337 prevents lung fibrosis in two complementary animal models and substantially attenuates PH in the Fra-2 mouse model. These findings confirm that the pan-PPAR agonist IVA337 is an appealing therapeutic candidate for these cardiopulmonary involvements. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Final Technical Report. Results of Phases 2-5

    SciTech Connect

    Narang, David; Ayyanar, Raja; Gemin, Paul; Baggu, Murali; Srinivasan, Devarajan

    2015-02-27

    APS’s renewable energy portfolio, driven in part by Arizona’s Renewable Energy Standard (RES) currently includes more than 1100 MW of installed capacity, equating to roughly 3000 GWh of annual production. Overall renewable production is expected to grow to 6000 GWh by 2025. It is expected that distributed photovoltaics, driven primarily by lower cost, will contribute to much of this growth and that by 2025, distributed installations will account for half of all renewable production (3000GHW). As solar penetration increases, additional analysis may be required for routine utility processes to ensure continued safe and reliable operation of the electric distribution network. Such processes include residential or commercial interconnection requests and load shifting during normal feeder operations. Circuits with existing high solar penetration will also have to be studied and results will need to be evaluated for adherence to utility practices or strategy. Increased distributed PV penetration may offer benefits such as load offsetting, but it also has the potential to adversely impact distribution system operation. These effects may be exacerbated by the rapid variability of PV production. Detailed effects of these phenomena in distributed PV applications continue to be studied. Comprehensive, high-resolution electrical models of the distribution system were developed to analyze the impacts of PV on distribution circuit protection systems (including coordination and anti-islanding), predict voltage regulation and phase balance issues, and develop volt/VAr control schemes. Modeling methods were refined by validating against field measurements. To augment the field measurements, methods were developed to synthesize high resolution load and PV generation data to facilitate quasi-static time series simulations. The models were then extended to explore boundary conditions for PV hosting capability of the feeder and to simulate common utility practices such as feeder

  1. Test results of the Phase 1 Test Plan

    SciTech Connect

    Hey, B.E.

    1995-03-01

    Radioactive waste materials in underground high level waste (HLW) storage tanks at the Hanford Site evolve gaseous mixtures at varying rates. In order to verify the flammability of these gases and the mechanisms by which they are produced, it is necessary to sample material from these tanks in such a way as to preserve the gas phase of the material for analysis. Careful laboratory studies could then be performed on these samples which would allow judgement to be made of the hazard level of the storage tank. The Retained Gas Sampler (RGS) system is such a sampling method. A multidisciplinary team developed and issued a plan to obtain waste tank core samples for gas phase analysis. This plan contained the basic idea and function of the RGS system. Different organizations assumed responsibility of various aspects of the RGS program which they were most qualified to develop.

  2. Bio-Plex immunoassay measuring the quantity of lysosomal N-acetylgalactosamine-6-sulfatase protein in dried blood spots for the screening of mucopolysaccharidosis IVA in newborn: a pilot study.

    PubMed

    Chuang, Chih-Kuang; Lin, Hsiang-Yu; Wang, Tuan-Jen; Huang, Sung-Fa; Lin, Shuan-Pei

    2017-07-13

    Mucopolysaccharidosis (MPS) IVA (Morquio syndrome A) is an autosomal-recessive lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-6-sulfatase (GALNS) resulting in excessive lysosomal storage of keratan sulfate. Treatments for MPS IVA have recently become available with optimal outcomes associated with early diagnosis and treatment which can be achieved by newborn screening. Newborn screening programme for MPS IVA pilot study. MacKay Memorial Hospital (MMH), Taipei and another three branch hospitals in Taiwan. A total of 7415 newborns were born in four branch hospitals of MMH and had joined the MPS IVA newborn screening programme. Written informed consents were obtained from parents prior to the screening process (12MMHIS188 approved by MacKay Memorial Hospital Institutional Review Board). An alternative newborn screening method for MPS IVA has been performed. Screening involved measuring the quantity of GALNS in dried blood spot (DBS) from newborn infants using the Bio-Plex immunoassay. The amount of fluorescence sorting detected by yttrium aluminium garnet laser was proportional to the quantity of GALNS protein. Of the 7415 neonates analysed, eight infants whose GALNS levels were below the cut-off value of 8.30 µg/L had been recalled for a second DBS collection. The reference values were 8.30-27.43 µg/L. In patients with confirmed MPS IVA (n=11), the GALNS quantities were far below 5% of the normal population. The Bio-Plex immunoassay is a validated method used for measuring GALNS protein in DBS and has the potential to be adopted for MPS IVA newborn screening study design. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. AB108. The appliance of Bio-Plex immunoassay using dried blood spots for mucopolysaccharidosis IVA newborn screening in Taiwan—a pilot study

    PubMed Central

    Lin, Chia-Hui; Chuang, Chih-Kuang; Lin, Hsiang-Yu; Wang, Tuen-Jen; Tsai, Chia-Chen; Lin, Shuan-Pei

    2015-01-01

    Background Mucopolysaccharidosis (MPS) IVA is an autosomal recessive lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-6-sulfatase (GALNS) resulting in excessive lysosomal storage of keratan sulfate. This excessive storage causes a systemic skeletal dysplasia, short stature, and joint abnormalities. Treatments for MPS IVA are available. Better outcomes are associated with early treatment, which highlights a need for newborn screening for MPS IVA. Methods We have conducted a newborn screening pilot program for MPS IVA since December 1, 2013. Screening involved measuring the quantity of GALNS in dried blood spots on filter paper (DBFP) from newborns using a Bio-Plex immunoassay. The amounts of fluorescence sorting detected by YAG laser with wavelengths of 532 (exciting) and 580 nm (emission) is proportional to the quantity of GALNS protein. Results More than 5,657 neonates have been analyzed, in those, 132 newborns had GALNS quantification less than the cut-off value (48.64 ρg/mL) at the first screening test. Most of them (n=124) were exclusive and only eight had been recalled for a second DBFP collection and GALNS quantity rechecked. The reference values were 48.64-552.4 ρg/mL. For the confirmed MPS IV patients without enzyme replacement therapy (n=11), the GALNS quantities were far less than 5% of the normal population, and ranged from 0.00 to 4.02 ρg/mL. The GALNS quantities of the carriers (n=2) were significantly reduced comparing with those of the normal values. Conclusions The Bio-Plex immunoassay has the potential to be adopted for newborn screening of MPS IVA. This method is reliable, sensitive, validated, simple, and cost-effective in measuring GALNS enzyme in DBFP.

  4. Phase II Study of Consolidation Chemotherapy After Concurrent Chemoradiation in Cervical Cancer: Preliminary Results

    SciTech Connect

    Choi, Chel Hun; Lee, Jeong-Won; Kim, Tae-Joong; Kim, Woo Young; Nam, Hee Rim; Kim, Byoung-Gie . E-mail: huna0@naver.com; Huh, Seung Jae; Lee, Je-Ho; Bae, Duk-Soo

    2007-07-01

    Purpose: Our aim was to determine the efficacy of consolidation chemotherapy after concurrent chemoradiation (CCRT) using high-dose-rate brachytherapy in patients with locally advanced cervical carcinoma. Methods and Materials: Patients with cervical carcinoma (FIGO stage IB2-IVA) were treated with external beam radiation therapy to the whole pelvis (50.4 Gy) and high-dose-rate brachytherapy (24 Gy to point A). Cisplatin 60 mg/m{sup 2} (Day 1) and 5-fluorouracil 1000 mg/m{sup 2} (Days 1-5) were given every 3 weeks starting concurrently with the radiation and followed by 3 more cycles of consolidation for a total of 6 cycles. Results: Thirty patients (94%) received 3 more cycles of post-CCRT consolidation chemotherapy and were evaluable for the toxicity and efficacy of consolidation. The most common toxicities of Grade 2 or higher were nausea or vomiting (47%) and anemia (33%). Late complications of the rectum and bladder occurred in 13% and 6% of the patients, respectively. The clinical complete response rate was 87% (95% CI, 75%-99%). During a median follow-up of 27 months (range, 6-58 months), 5 patients (17%) had recurrence; the sites of failure were 3 (10%) inside the radiation field and 2 (7%) outside the radiation field. The estimated 3-year progression-free survival rate was 83% (95% CI, 67%-99%) and overall survival rate was 91% (95% CI, 79%-100%). Conclusions: Consolidation chemotherapy after CCRT is well tolerated and effective in patients with locally advanced cervical carcinoma. A prospective randomized trial to compare this treatment strategy with standard CCRT seems to be worthwhile.

  5. Inhibitory effects of 1alpha, 25dihydroxyvitamin D3 and Ajuga iva extract on oxidative stress, toxicity and hypo-fertility in diabetic rat testes.

    PubMed

    Hamden, K; Carreau, S; Jamoussi, K; Ayadi, F; Garmazi, F; Mezgenni, N; Elfeki, A

    2008-09-01

    The aim of the current study is to investigate the therapeutic and preventive effects of 1alpha, 25dihydroxyvitaminD3 (1,25 (OH)2 D3) and Afuga iva (AI) extract on diabetes toxicity in rats testes. Thus diabetic rats were treated with 1alpha, 25dihydroxyvitaminD3 or Ajuga iva extract as both therapeutic and preventive treatments on diabetes toxicity in rats testes. Our results showed that diabetes induced a decrease in testosterone and 17beta-estradiol levels in testes and plasma. Besides, a fall in testicular antioxidant capacity appeared by a decrease in both antioxidant (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities) and nonenzymatic antioxidant (copper (Cu), magnesium (Mg) and iron (Fe) levels). All theses changes enhanced testicular toxicity (increase in testicular aspartate amino transaminase (AST), alanine amino transaminase (ALT), lactate dehydrogenase (LDH) activities and the lipid peroxidation and triglyceride (TG) levels). In addition, a decrease in testicular total cholesterol (TCh) level was observed in diabetic rats testes. All the changes lead to a decrease in the total number and mobility of epididymal spermatozoa. The administration of 1alpha,25dihydroxyvitaminD3 and Ajuga iva extract three weeks before and after diabetes induction interfered and prevented diabetes toxicity in the reproductive system. 1,25 (OH)2 D3 and Ajuga iva extract blunted all changes observed in diabetic rats. To sum up, the data suggested that 1,25 (OH)2 D3 and Ajuga iva extract have a protective effect on alloxan-induced damage in reproductive system by enhancing the testosterone and 17beta-estradiol levels, consequently protecting from oxidative stress, cellular toxicity and maintaining the number and motility of spermatozoids.

  6. Development of MPS IVA mouse (Galnstm(hC79S.mC76S)slu) tolerant to human N-acetylgalactosamine-6-sulfate sulfatase.

    PubMed

    Tomatsu, Shunji; Gutierrez, Monica; Nishioka, Tatsuo; Yamada, Masamichi; Yamada, Mana; Tosaka, Yasuhiro; Grubb, Jeffrey H; Montaño, Adriana M; Vieira, Matheus B; Trandafirescu, Georgeta G; Peña, Olga M; Yamaguchi, Seiji; Orii, Koji O; Orii, Tadao; Noguchi, Akihiko; Laybauer, Leticia

    2005-11-15

    Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disease caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency. In recent studies of enzyme replacement therapy for animal models with lysosomal storage diseases, cellular and humoral immune responses to the injected enzymes have been recognized as major impediments to effective treatment. To study the long-term effectiveness and side effects of therapies in the absence of immune responses, we have developed an MPS IVA mouse model, which has many similarities to human MPS IVA and is tolerant to human GALNS protein. We used a construct containing both a transgene (cDNA) expressing inactive human GALNS in intron 1 and an active site mutation (C76S) in adjacent exon 2 and thereby introduced both the inactive cDNA and the C76S mutation into the murine Galns by targeted mutagenesis. Affected homozygous mice have no detectable GALNS enzyme activity and accumulate glycosaminoglycans in multiple tissues including visceral organs, brain, cornea, bone, ligament and bone marrow. At 3 months, lysosomal storage is marked within hepatocytes, reticuloendothelial Kupffer cells, and cells of the sinusoidal lining of the spleen, neurons and meningeal cells. The bone storage is also obvious, with lysosomal distention in osteoblasts and osteocytes lining the cortical bone, in chondrocytes and in the sinus lining cells in bone marrow. Ubiquitous expression of the inactive human GALNS was also confirmed by western blot using the anti-GALNS monoclonal antibodies newly produced, which resulted in tolerance to immune challenge with human enzyme. The newly generated MPS IVA mouse model should provide a good model to evaluate long-term administration of enzyme replacement.

  7. SecA is required for membrane targeting of the cell division protein DivIVA in vivo

    PubMed Central

    Halbedel, Sven; Kawai, Maki; Breitling, Reinhard; Hamoen, Leendert W.

    2014-01-01

    The conserved protein DivIVA is involved in different morphogenetic processes in Gram-positive bacteria. In Bacillus subtilis, the protein localizes to the cell division site and cell poles, and functions as a scaffold for proteins that regulate division site selection, and for proteins that are required for sporulation. To identify other proteins that bind to DivIVA, we performed an in vivo cross-linking experiment. A possible candidate that emerged was the secretion motor ATPase SecA. SecA mutants have been described that inhibit sporulation, and since DivIVA is necessary for sporulation, we examined the localization of DivIVA in these mutants. Surprisingly, DivIVA was delocalized, suggesting that SecA is required for DivIVA targeting. To further corroborate this, we performed SecA depletion and inhibition experiments, which provided further indications that DivIVA localization depends on SecA. Cell fractionation experiments showed that SecA is important for binding of DivIVA to the cell membrane. This was unexpected since DivIVA does not contain a signal sequence, and is able to bind to artificial lipid membranes in vitro without support of other proteins. SecA is required for protein secretion and membrane insertion, and therefore its role in DivIVA localization is likely indirect. Possible alternative roles of SecA in DivIVA folding and/or targeting are discussed. PMID:24592260

  8. High expression of N-acetylglucosaminyltransferase IVa promotes invasion of choriocarcinoma.

    PubMed

    Niimi, K; Yamamoto, E; Fujiwara, S; Shinjo, K; Kotani, T; Umezu, T; Kajiyama, H; Shibata, K; Ino, K; Kikkawa, F

    2012-12-04

    Gestational trophoblastic diseases (GTDs) are related to trophoblasts, and human chorionic gonadotropin (hCG) is secreted by GTDs as well as normal placentas. However, the asparagine-linked sugar chains on hCG contain abnormal biantennary structures in invasive mole and choriocarcinoma, but not normal pregnancy or hydatidiform mole. N-acetylglucosaminyltransferase-IV (GnT-IV) catalyses β1,4-N-acetylglucosamine branching on asparagine-linked oligosaccharides, which are consistent with the abnormal sugar chain structures on hCG. We investigated GnT-IVa expression in GTDs and placentas by immunohistochemistry, western blot, and RT-PCR. We assessed the effects of GnT-IVa knockdown in choriocarcinoma cells in vitro and in vivo. The GnT-IVa was highly expressed in trophoblasts of invasive mole and choriocarcinoma, and moderately in extravillous trophoblasts during the first trimester, but not in hydatidiform mole or other normal trophoblasts. The GnT-IVa knockdown in choriocarcinoma cells significantly reduced migration and invasive capacities, and suppressed cellular adhesion to extracellular matrix proteins. The extent of β1,4-N-acetylglucosamine branching on β1 integrin was greatly reduced by GnT-IVa knockdown, although the expression of β1 integrin was not changed. In vivo studies further demonstrated that GnT-IVa knockdown suppressed tumour engraftment and growth. These findings suggest that GnT-IVa is involved in regulating invasion of choriocarcinoma through modifications of the oligosaccharide chains of β1 integrin.

  9. Multimodal treatment for stage IVA thymoma: a proposable strategy.

    PubMed

    Rena, Ottavio; Mineo, Tommaso Claudio; Casadio, Caterina

    2012-04-01

    A retrospective review of a series of consecutive patients was carried out to evaluate the feasibility and the efficacy of a multimodal treatment in the management of stage IVA thymoma at first diagnosis. From 1998 to 2008, 18 patients affected by stage IVA thymoma underwent neoadjuvant chemotherapy, surgery and subsequent mediastinal radiation therapy. There were 10 males and 8 females, mean age 54.5 years (range 29-68). Not specific symptoms were present in 12 cases and thymus-related syndromes were reported in 4. Histological subtypes were 1 AB, 2 B1, 4 B2, 7 B3, 1 mixed B1-B2, 1 mixed B1-B3 and 2 mixed B2-B3 thymomas. Neoadjuvant chemotherapy (4 courses of cisplatin-based chemotherapy) was well tolerated in all cases. Those patients demonstrating clinical response at restaging (16/18) received surgical resection: "en-bloc" thymoma, residual thymic tissue and tumour involved organs resection was carried out together with the pleural implants removal. Complete macroscopic resection was achieved 10/16 patients (64%). Postoperative mortality and morbidity were null and 24%, respectively. Adjuvant radiation therapy consisted of 45-54 Gy administered by a 6 MV linear accelerator to the whole mediastinum and previous tumour bed. Mean follow-up was 82±33 months (range 31-143); overall survival was 85% and 53% at 5- and 10-years. Disease-related survival of the entire cohort was 100% and 58% at 5- and 10-years, whereas freedom from relapse survival for patients submitted to complete resection was 58% and 42% at 5- and 10-years. Disease-related survival when complete and not complete resection were considered were 100% and 52% and 72% and 0% at 5- and 10-years respectively (p=0.048). Multimodal management based on induction chemotherapy, subsequent surgery and postoperative mediastinal radiation allows a good complete resection rate and it is demonstrated to be a safe and effective treatment to warrant a good long-term survival in stage IVA thymoma patients.

  10. Phase separated membrane bioreactor - Results from model system studies

    NASA Technical Reports Server (NTRS)

    Petersen, G. R.; Seshan, P. K.; Dunlop, E. H.

    1989-01-01

    The operation and evaluation of a bioreactor designed for high intensity oxygen transfer in a microgravity environment is described. The reactor itself consists of a zero headspace liquid phase separated from the air supply by a long length of silicone rubber tubing through which the oxygen diffuses in and the carbon dioxide diffuses out. Mass transfer studies show that the oxygen is film diffusion controlled both externally and internally to the tubing and not by diffusion across the tube walls. Methods of upgrading the design to eliminate these resistances are proposed. Cell growth was obtained in the fermenter using Saccharomyces cerevisiae showing that this concept is capable of sustaining cell growth in the terrestrial simulation.

  11. Phase 1 results from the Stirling-powered vehicle project

    NASA Technical Reports Server (NTRS)

    Shaltens, Richard K.

    1988-01-01

    The NASA Technology Utilization (TU) Office is sponsoring a multiyear, multiphase demonstration program to assess the technology developed under the DOE/NASA automotive Stirling engine (ASE) program with engines installed in various Air Force vehicles while being evaluated by independent third parties under realistic conditions. This paper reviews the operational history of Phase 1 with a Mod 1 Stirling engine installed in an Air Force multistop van in a variety of missions. Ten months of operation were with Air Force personnel at Langley Air Force Base, Virginia, where over 1100 hr and 4000 mi were logged on the Langley flight line. The Stirling-powered van operated on unleaded gasoline, JP-4 aircraft fuel, and diesel fuel at Langley Air Force Base. Two months of operation were completed with Deere and Company personnel in the Moline, Illinois area where over 175 hr and 2650 mi were logged on a Deere mail delivery route.

  12. Phase separated membrane bioreactor - Results from model system studies

    NASA Technical Reports Server (NTRS)

    Petersen, G. R.; Seshan, P. K.; Dunlop, E. H.

    1989-01-01

    The operation and evaluation of a bioreactor designed for high intensity oxygen transfer in a microgravity environment is described. The reactor itself consists of a zero headspace liquid phase separated from the air supply by a long length of silicone rubber tubing through which the oxygen diffuses in and the carbon dioxide diffuses out. Mass transfer studies show that the oxygen is film diffusion controlled both externally and internally to the tubing and not by diffusion across the tube walls. Methods of upgrading the design to eliminate these resistances are proposed. Cell growth was obtained in the fermenter using Saccharomyces cerevisiae showing that this concept is capable of sustaining cell growth in the terrestrial simulation.

  13. Phase separated membrane bioreactor: Results from model system studies

    NASA Astrophysics Data System (ADS)

    Petersen, G. R.; Seshan, P. K.; Dunlop, E. H.

    The operation and evaluation of a bioreactor designed for high intensity oxygen transfer in a microgravity environment is described. The reactor itself consists of a zero headspace liquid phase separated from the air supply by a long length of silicone rubber tubing through which the oxygen diffuses in and the carbon dioxide diffuses out. Mass transfer studies show that the oxygen is film diffusion controlled both externally and internally to the tubing and not by diffusion across the tube walls. Methods of upgrading the design to eliminate these resistances are proposed. Cell growth was obtained in the fermenter using Saccharomyces cerevisiae showing that this concept is capable of sustaining cell growth in the terrestial simulation.

  14. Phase separated membrane bioreactor: results from model system studies.

    PubMed

    Petersen, G R; Seshan, P K; Dunlop, E H

    1989-01-01

    The operation and evaluation of a bioreactor designed for high intensity oxygen transfer in a microgravity environment is described. The reactor itself consists of a zero headspace liquid phase separated from the air supply by a long length of silicone rubber tubing through which the oxygen diffuses in and the carbon dioxide diffuses out. Mass transfer studies show that the oxygen is film diffusion controlled both externally and internally to the tubing and not by diffusion across the tube walls. Methods of upgrading the design to eliminate these resistances are proposed. Cell growth was obtained in the fermenter using Saccharomyces cerevisiae showing that this concept is capable of sustaining cell growth in the terrestrial [correction of terrestial] simulation.

  15. Results from the Stirling-powered vehicle project: Phase 1

    SciTech Connect

    Shaltens, R.K.

    1988-01-01

    The NASA Technology Utilization (TU) Office is sponsoring a multiyear, multiphase demonstration program to assess the technology developed under the DOE/NASA automotive Stirling engine (ASE) program with engines installed in various Air Force vehicles while being evaluated by independent third parties under realistic conditions. This paper reviews the operational history of Phase I and a Mod I Stirling engine installed in an Air Force multistop van in a variety of missions. Ten months of operation were with Air Force personnel at Langley Air Force Base, Virginia, where over 1100 hr and 4000 mi were logged on the Langley flight line. The Stirling-powered van was operated on unleaded gasoline, JP-4 aircraft fuel, and diesel fuel at Langley Air Force Base. Two months of operation were completed with Deere Company personnel in the Moline, Illinois, area where over 175 h and 2650 miles were logged on a Deere mail delivery route. 8 refs., 12 figs., 6 tabs.

  16. Silica Waste Utilisation Phase II - Preliminary Laboratory Results

    SciTech Connect

    Lund, J.W.; Boyd, T.L.

    1995-01-01

    A second phase of laboratory testing is being performed on waste silica from the Cerro Prieto geothermal field in Mexico. The main objective is to produce mixes of various combinations of hydrated lime, portland cement, and plastic fibers with the waste silica from disposal ponds to determine their suitability for use as insulating bricks in low cost housing. Silica-cement mixtures appear to have the highest flexural strength and resistance to weathering. Silica-lime mixtures appear to have the best insulating properties (lowest thermal conductivity). The addition of plastic fibers to the silica-lime mixture appears to improve both strength and weather resistance. Work is still in progress and will be completed in 1996 with the construction of various test walls in the Mexicali, Mexico area.

  17. Overvoltages in underground systems, phase 2 results. Final report

    SciTech Connect

    Mata, C.T.; Fernandez, M.I.; Rakov, V.A.; Uman, M.A.; Bejleri, M.; Rambo, K.J.; Stapleton, M.V.

    1998-12-01

    In 1993, a research facility was constructed by Power Technologies, Inc. (PTI) under the funding and direction of the Electric Power Research Institute (EPRI) at the Camp Blanding Florida Army National Guard Base, located approximately midway between Gainesville and Jacksonville, Florida, for the specific purpose of studying lightning`s interaction with power distribution systems. This report is primarily based on Camp Blanding experiments conducted by the University of Florida (UF) from 1994 to 1998 and experiments conducted by PTI in 1993. The responses (currents and voltages) of the test system are presented for ten cases representing the following lightning strike points and test-system configurations: two triggered strikes and one natural strike to the phase conductor of the overhead line while the underground distribution system was connected to the line; two triggered strikes to ground tens of meters from the underground cable (one at 20 meters from the line and one at 125 m from the line) and one natural strike to ground tens of meters from the cable (and from the line) while the underground system was connected to the line; two triggered strikes to the line (one to the phase conductor and one to the neutral conductor) with no connection to the underground system 80 meters away; one triggered strike to ground 20 m from the line (without MOV arresters), with no connection to the underground system 60 m away; one strike to ground surface between two cables buried about 5 m apart and at a depth of about 1 m. EMTP modeling is used to simulate lightning interaction with power distribution system. Conditions at the lightning channel termination on ground are analyzed.

  18. Phase imaging results of phase defect using micro-coherent extreme ultraviolet scatterometry microscope

    NASA Astrophysics Data System (ADS)

    Harada, Tetsuo; Hashimoto, Hiraku; Amano, Tsuyoshi; Kinoshita, Hiroo; Watanabe, Takeo

    2016-04-01

    To evaluate defects on extreme ultraviolet (EUV) masks at the blank state of manufacturing, we developed a micro-coherent EUV scatterometry microscope (micro-CSM). The illumination source is coherent EUV light with a 140 nm focus diameter on the defect using a Fresnel zone plate. This system directly observes the reflection and diffraction signals from a phase defect. The phase and the intensity image of the defect are reconstructed with the diffraction images using ptychography, which is an algorithm of the coherent diffraction imaging. We observed programmed phase defect on a blank EUV mask. Phase distributions of these programmed defects were well reconstructed quantitatively. The micro-CSM is a very powerful tool to review an EUV phase defect.

  19. Chikusetsusaponin IVa methyl ester induces cell cycle arrest by the inhibition of nuclear translocation of β-catenin in HCT116 cells

    SciTech Connect

    Lee, Kyung-Mi; Yun, Ji Ho; Lee, Dong Hwa; Park, Young Gyun; Son, Kun Ho; Nho, Chu Won; Kim, Yeong Shik

    2015-04-17

    We demonstrate that chikusetsusaponin IVa methyl ester (CME), a triterpenoid saponin from the root of Achyranthes japonica, has an anticancer activity. We investigate its molecular mechanism in depth in HCT116 cells. CME reduces the amount of β-catenin in nucleus and inhibits the binding of β-catenin to specific DNA sequences (TCF binding elements, TBE) in target gene promoters. Thus, CME appears to decrease the expression of cell cycle regulatory proteins such as Cyclin D1, as a representative target for β-catenin, as well as CDK2 and CDK4. As a result of the decrease of the cell cycle regulatory proteins, CME inhibits cell proliferation by arresting the cell cycle at the G0/G1 phase. Therefore, we suggest that CME as a novel Wnt/β-catenin inhibitor can be a putative agent for the treatment of colorectal cancers. - Highlights: • CME inhibits cell proliferation in HCT116 cells. • CME increases cell cycle arrest at G0/G1 phase and apoptosis. • CME attenuates cyclin D1 and regulates cell cycle regulatory proteins. • CME inhibits β-catenin translocation to nucleus.

  20. HESTIA Phase I Test Results: The Air Revitalization System

    NASA Technical Reports Server (NTRS)

    Wright, Sarah E.; Hansen, Scott W.

    2016-01-01

    In any human spaceflight mission, a number of Environmental Control & Life Support System (ECLSS) technologies work together to provide the conditions astronauts need to live healthily, productively, and comfortably in space. In a long-duration mission, many of these ECLSS technologies may use materials supplied by In-Situ Resource Utilization (ISRU), introducing more interactions between systems. The Human Exploration Spacecraft Test-bed for Integration & Advancement (HESTIA) Project aims to create a test-bed to evaluate ECLSS and ISRU technologies and how they interact in a high-fidelity, closed-loop, human-rated analog habitat. Air purity and conditioning are essential components within any ECLSS and for HESTIA's first test they were achieved with the Air Revitalization System (ARS) described below. The ARS provided four essential functions to the test-bed chamber: cooling the air, removing humidity from the air, removing trace contaminants, and scrubbing carbon dioxide (CO2) from the air. In this case, the oxygen supply function was provided by ISRU. In the current configuration, the ARS is a collection of different subsystems. A fan circulates the air, while a condensing heat exchanger (CHX) pulls humidity out of the air. A Trace Contaminant Removal System (TCRS) filters the air of potentially harmful contaminants. Lastly, a Reactive Plastic Lithium Hydroxide (RP-LiOH) unit removes CO2 from the breathing air. During the HESTIA Phase I test in September 2015, the ARS and its individual components each functioned as expected, although further analysis is underway. During the Phase I testing and in prior bench-top tests, the energy balance of heat removed by the CHX was not equal to the cooling it received. This indicated possible instrument error and therefore recalibration of the instruments and follow-up testing is planned in 2016 to address the issue. The ARS was tested in conjunction with two other systems: the Human Metabolic Simulator (HMS) and the

  1. ECLIPS at LMD: Preliminary results of phase 2

    NASA Technical Reports Server (NTRS)

    Valentin, R.; Menenger, L.; Elouragini, S.; Flamant, P. H.; Pelon, J.

    1992-01-01

    The LMD (Laboratoire de Meteorologie Dynamique) ground-based backscatter lidar station (48 degrees 4 N, 02 degrees 0 E) near Paris was operated daily during the phase 2 of the Experimental Closed Lidar Pilot Study (ECLIPS) from May 22 to June 19, 1991 simultaneously with a radiometric equipment recording the downward short wavelength (SW) and long wavelength (LW) fluxes. A day-by-day summary of the field measurement as a function of universal time (UT) is given. Considering a 5 days week, there are only two days of missing data (05/31 and 06/06) in our record. The nearby meteorological station (10 km away) provides rawindsounding at 00UT and 12UT. During two days, the French airborne lidar LEANDRE was flown over the ground-based station. The airborne equipment looked down while the ground based equipment looked up. The two lidars were operated at 532 nm, and the on-board radiometers were identical to the ones on the ground. The measurements were synchronized with Advanced Very High Resolution Radiometer (AVHIRR) overpasses as required. We also indicate the Meteosat data corresponding to the period of measurements. Two examples of simultaneous ground-based lidar, pygeometer and pyranometer data are displayed.

  2. ECLIPS at LMD: Preliminary results of phase 2

    NASA Technical Reports Server (NTRS)

    Valentin, R.; Menenger, L.; Elouragini, S.; Flamant, P. H.; Pelon, J.

    1992-01-01

    The LMD (Laboratoire de Meteorologie Dynamique) ground-based backscatter lidar station (48 degrees 4 N, 02 degrees 0 E) near Paris was operated daily during the phase 2 of the Experimental Closed Lidar Pilot Study (ECLIPS) from May 22 to June 19, 1991 simultaneously with a radiometric equipment recording the downward short wavelength (SW) and long wavelength (LW) fluxes. A day-by-day summary of the field measurement as a function of universal time (UT) is given. Considering a 5 days week, there are only two days of missing data (05/31 and 06/06) in our record. The nearby meteorological station (10 km away) provides rawindsounding at 00UT and 12UT. During two days, the French airborne lidar LEANDRE was flown over the ground-based station. The airborne equipment looked down while the ground based equipment looked up. The two lidars were operated at 532 nm, and the on-board radiometers were identical to the ones on the ground. The measurements were synchronized with Advanced Very High Resolution Radiometer (AVHIRR) overpasses as required. We also indicate the Meteosat data corresponding to the period of measurements. Two examples of simultaneous ground-based lidar, pygeometer and pyranometer data are displayed.

  3. CryoSat-2 commissioning phase results summary

    NASA Astrophysics Data System (ADS)

    Cullen, R.

    2010-12-01

    CryoSat-2 was launched on 8th April 2010 and following a 3 day LEOP entered its 6 month commissioning phase. The primary payload of the platform consists of the Synthetic Interferometric Radar Altimeter (SIRAL-2) with support for its data processing coming from data acquired from on-board DORIS DGXX and star trackers. We present a description of the payload and provide post-launch performance summaries in terms of SIRAL internal/external calibration in combination with an assessment of global data acquisition achievement in each of the three science modes: Low resolution pulse-width limited mode (LRM) over interior land-ice and ocean to support POD, Synthetic aperture radar mode (SARM) for sea-ice and SAR interferometric mode (SARInM) for higher surface slope land-ice sheet margin acquisitions. Commissioning activities are summarised with examples and we provide conclusions on the experiences gained with the data during this period. Specific issues are highlighted and that Users of the data products should consider taking into account with their analyses. Finally, present performances of the three science modes over transponders and open ocean calibration zones are provided in addition to specific cases over land and sea ice. Preliminary performances of DORIS and star trackers will be provided in the context of overall SIRAL performance.

  4. Inductive voltage adder (IVA) for submillimeter radius electron beam

    SciTech Connect

    Mazarakis, M.G.; Poukey, J.W.; Maenchen, J.E.

    1996-12-31

    The authors have already demonstrated the utility of inductive voltage adder accelerators for production of small-size electron beams. In this approach, the inductive voltage adder drives a magnetically immersed foilless diode to produce high-energy (10--20 MeV), high-brightness pencil electron beams. This concept was first demonstrated with the successful experiments which converted the linear induction accelerator RADLAC II into an IVA fitted with a small 1-cm radius cathode magnetically immersed foilless diode (RADLAC II/SMILE). They present here first validations of extending this idea to mm-scale electron beams using the SABRE and HERMES-III inductive voltage adders as test beds. The SABRE experiments are already completed and have produced 30-kA, 9-MeV electron beams with envelope diameter of 1.5-mm FWHM. The HERMES-III experiments are currently underway.

  5. Chikusetsusaponin IVa Butyl Ester (CS-IVa-Be), a Novel IL6R Antagonist, Inhibits IL6/STAT3 Signaling Pathway and Induces Cancer Cell Apoptosis.

    PubMed

    Yang, Jie; Qian, Shihui; Cai, Xueting; Lu, Wuguang; Hu, Chunping; Sun, Xiaoyan; Yang, Yang; Yu, Qiang; Gao, S Paul; Cao, Peng

    2016-06-01

    The activation of IL6/STAT3 signaling is associated with the pathogenesis of many cancers. Agents that suppress IL6/STAT3 signaling have cancer-therapeutic potential. In this study, we found that chikusetsusaponin IVa butyl ester (CS-IVa-Be), a triterpenoid saponin extracted from Acanthopanas gracilistylus W.W.Smith, induced cancer cell apoptosis. CS-IVa-Be inhibited constitutive and IL6-induced STAT3 activation, repressed STAT3 DNA-binding activity, STAT3 nuclear translocation, IL6-induced STAT3 luciferase reporter activity, IL6-induced STAT3-regulated antiapoptosis gene expression in MDA-MB-231 cells, and IL6-induced TF-1 cell proliferation. Surprisingly, CS-IVa-Be inhibited IL6 family cytokines rather than other cytokines induced STAT3 activation. Further studies indicated that CS-IVa-Be is an antagonist of IL6 receptor via directly binding to the IL6Rα with a Kd of 663 ± 74 nmol/L and the GP130 (IL6Rβ) with a Kd of 1,660 ± 243 nmol/L, interfering with the binding of IL6 to IL6R (IL6Rα and GP130) in vitro and in cancer cells. The inhibitory effect of CS-IVa-Be on the IL6-IL6Rα-GP130 interaction was relatively specific as CS-IVa-Be showed higher affinity to IL6Rα than to LIFR (Kd: 4,910 ± 1,240 nmol/L) and LeptinR (Kd: 4,990 ± 915 nmol/L). We next demonstrated that CS-IVa-Be not only directly induced cancer cell apoptosis but also sensitized MDA-MB-231 cells to TRAIL-induced apoptosis via upregulating DR5. Our findings suggest that CS-IVa-Be as a novel IL6R antagonist inhibits IL6/STAT3 signaling pathway and sensitizes the MDA-MB-231 cells to TRAIL-induced cell death. Mol Cancer Ther; 15(6); 1190-200. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. Antioxidant effect of Ajuga iva aqueous extract in streptozotocin-induced diabetic rats.

    PubMed

    Taleb-Senouci, D; Ghomari, H; Krouf, D; Bouderbala, S; Prost, J; Lacaille-Dubois, M A; Bouchenak, M

    2009-06-01

    The purpose of this study was to investigate the possible antioxidant effect of an aqueous extract of Ajuga iva (Ai) in streptozotocin (STZ)-induced diabetic rats. Twelve diabetic rats were divided into two groups fed a casein diet supplemented or not with Ai (0.5%), for 4 weeks. In vitro, the Ai extract possessed a very high antioxidant effect (1 mg/ml was similar to those of trolox 300 mmol/l). The results indicated that plasma thiobarbituric acid reactive substances (TBARS) values were reduced by 41% in Ai-treated compared with untreated diabetic rats. TBARS concentrations were lower 1.5-fold in liver, 1.8-fold in heart, 1.9-fold in muscle and 2.1-fold in brain in Ai-treated than untreated group. In erythrocytes, Ai treatment increased significantly the activities of glutathione peroxidase (GSH-Px) (+25%) and glutathione reductase (GSSH-Red) (+22%). Superoxide dismutase activity was increased in muscle (+22%), while GSH-Px activity was significantly higher in liver (+28%), heart (+40%) and kidney (+45%) in Ai-treated compared with untreated group. Liver and muscle GSSH-Red activity was, respectively, 1.6- and 1.5-fold higher in Ai-treated than untreated diabetic group. Catalase activity was significantly increased in heart (+36%) and brain (+32%) in Ai-treated than untreated group. Ai treatment decreased plasma nitric oxide (-33%), carbonyls (-44%) and carotenoids (-68%) concentrations. In conclusion, this study indicates that Ajuga iva aqueous extract improves the antioxidant status by reducing lipid peroxidation and enhancing the antioxidant enzymes activities in plasma, erythrocytes and tissues of diabetic rats.

  7. Autonomous Airborne Refueling Demonstration, Phase I Flight-Test Results

    NASA Technical Reports Server (NTRS)

    Dibley, Ryan P.; Allen, Michael J.; Nabaa, Nassib

    2007-01-01

    The first phase of the Autonomous Airborne Refueling Demonstration (AARD) project was completed on August 30, 2006. The goal of this 15-month effort was to develop and flight-test a system to demonstrate an autonomous refueling engagement using the Navy style hose-and-drogue air-to-air refueling method. The prime contractor for this Defense Advanced Research Projects Agency (DARPA) sponsored program was Sierra Nevada Corporation (SNC), Sparks, Nevada. The responsible flight-test organization was the NASA Dryden Flight Research Center (DFRC), Edwards, California, which also provided the F/A-18 receiver airplane (McDonnell Douglas, now The Boeing Company, Chicago, Illinois). The B-707-300 tanker airplane (The Boeing Company) was contracted through Omega Aerial Refueling Services, Inc., Alexandria, Virginia, and the optical tracking system was contracted through OCTEC Ltd., Bracknell, Berkshire, United Kingdom. Nine research flights were flown, testing the functionality and performance of the system in a stepwise manner, culminating in the plug attempts on the final flight. Relative position keeping was found to be very stable and accurate. The receiver aircraft was capable of following the tanker aircraft through turns while maintaining its relative position. During the last flight, six capture attempts were made, two of which were successful. The four misses demonstrated excellent characteristics, the receiver retreating from the drogue in a controlled, safe, and predictable manner that precluded contact between the drogue and the receiver aircraft. The position of the receiver aircraft when engaged and in position for refueling was found to be 5.5 to 8.5 ft low of the ideal position. The controller inputs to the F/A-18 were found to be extremely small

  8. Autonomous Airborne Refueling Demonstration: Phase I Flight-Test Results

    NASA Technical Reports Server (NTRS)

    Dibley, Ryan P.; Allen, Michael J.; Nabaa, Nassib

    2007-01-01

    The first phase of the Autonomous Airborne Refueling Demonstration (AARD) project was completed on August 30, 2006. The goal of this 15-month effort was to develop and flight-test a system to demonstrate an autonomous refueling engagement using the Navy style hose-and-drogue air-to-air refueling method. The prime contractor for this Defense Advanced Research Projects Agency (DARPA) sponsored program was Sierra Nevada Corporation (SNC), Sparks, Nevada. The responsible flight-test organization was the National Aeronautics and Space Administration (NASA) Dryden Flight Research Center (DFRC), Edwards, California, which also provided the F/A-18 receiver airplane (McDonnell Douglas, now The Boeing Company, Chicago, Illinois). The B-707-300 tanker airplane (The Boeing Company) was contracted through Omega Aerial Refueling Services, Inc., Alexandria, Virginia, and the optical tracking system was contracted through OCTEC Ltd., Bracknell, Berkshire, United Kingdom. Nine research flights were flown, testing the functionality and performance of the system in a stepwise manner, culminating in the plug attempts on the final flight. Relative position keeping was found to be very stable and accurate. The receiver aircraft was capable of following the tanker aircraft through turns while maintaining its relative position. During the last flight, six capture attempts were made, two of which were successful. The four misses demonstrated excellent characteristics, the receiver retreating from the drogue in a controlled, safe, and predictable manner that precluded contact between the drogue and the receiver aircraft. The position of the receiver aircraft when engaged and in position for refueling was found to be 5.5 to 8.5 ft low of the ideal position. The controller inputs to the F/A-18 were found to be extremely small.

  9. Mars Reconnaissance Orbiter: Integrating Results From the Primary Science Phase

    NASA Astrophysics Data System (ADS)

    Zurek, R. W.; Smrekar, S. E.

    2008-12-01

    The Mars Reconnaissance Orbiter (MRO) recently completed its one-Mars-year Primary Science Phase, observing the Martian atmosphere, surface and subsurface with 7 science investigations using 6 science instruments and tracking of the spacecraft as it orbited Mars. In addition, an eighth investigation made use of the onboard accelerometers during a 5-month period of MRO aerobraking to characterize upper atmospheric structure. Hallmarks-and challenges-of the MRO science mission have been: 1) unprecedented spatial resolution at all wavelengths used when observing from orbit; 2) coordinated imaging of local areas; and 3) the balancing of mapping, regional survey, and targeted observation of selected locales, frequently including repeat observations for stereo or for change detection. This talk will give an overview of the data return, including coverage in various observing modes, and will review how the various data sets have combined to provide new perspectives in our attempts to understand Mars, its present climate and its past evolution. Examples include the combination of surface compositional and morphologic information--on scales comparable to those examined by a terrestrial field geologist-to understand modification of the surface, revelations of the interior structure of the polar ice caps and of ice-rich deposits elsewhere which illuminate climate changes in recent geologic time, and monitoring of modern day variations, particularly as they reveal seasonal and inter-annual redistribution of dust and water, but also as they characterize ongoing mass wasting and cratering of the surface. Together, these all point to a complex history of change on Mars, with alternating episodes of significant water activity early in the planet's history, but with some water activity occurring in later geologic times, including the modern era.

  10. CBI Project Evaluation Phase II: Data Analysis Results.

    ERIC Educational Resources Information Center

    George Mason Univ., Fairfax, VA. Center for Interactive Educational Technology.

    This report contains the data and results of a study conducted in each of the five Department of Defense Dependents Schools worldwide concerning uses of and attitudes about computers in the classroom. Questionnaires were distributed to 6,850 students in grades 5 to 12 and to 543 computer-based instruction (CBI) project teachers. Highlights of the…

  11. Meteoritic Versus Biotic Amino Acids: An Update on Aib and Iva

    NASA Astrophysics Data System (ADS)

    Brückner, H.; Degenkolb, T.; Fox, S.

    2016-08-01

    Biotically synthesized Aib and Iva hav been found in >1,350 structurally characterized microbial peptides. However, the structural diversity of the non-proteinogenic amino acids in CM-type meteorites is not displayed in individual fungal peptides.

  12. Patient Preferences in Making Treatment Decisions in Patients With Stage I-IVA Oropharyngeal Cancer

    ClinicalTrials.gov

    2015-09-01

    Stage I Squamous Cell Carcinoma of the Oropharynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Tongue Cancer

  13. Orbit transfer vehicle engine study. Phase A: Continuation (study results)

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Studies included: selection of boost pump designs for low NPSH operation and generation of associated programmatic data; evaluation of OTV engine operation at intermediate thrust levels and impact on programmatics; and assessments of OTV engine operation at idle-mode thrusts under conditions experienced during aerobraking maneuvers of the ABOTV. As a result of the studies, it was recommended that the original OTV boost pump designs be used without change for low NPSH operation. Intermediate thrust operation is feasible for both the expander cycle and staged combustion cycles.

  14. Er:YAG clinical results on hard tissue: phase I

    NASA Astrophysics Data System (ADS)

    Cozean, Colette D.; Powell, G. L.

    1998-04-01

    Objective: This study was performed in order to establish that the pulpal and dentinal tissue are safe when exposed to the 2.94 micron pulsed Er:YAG laser radiation for the procedures of caries removal, cavity preparation, and etching prior to acid etching. This presentation discusses the histological results of a double-blind study comparing a pulsed Er:YAG with a standard dental drill. Methods: A double-blind histological evaluation of the pulpal and dentinal tissue changes induced by the Erbium laser and the dental drill was conducted on teeth extracted immediately following the dental procedure and at various intervals up to 1 year post-treatment. A statistical analysis was used to determine if any statistically significant clinical differences in dental tissue response could be observed between the Er:YAG laser and the standard dental drill. Conclusions: Analysis of the results indicated there were no significant differences observed between the laser and control groups in this study.

  15. Iron phase transformations resulting from the respiration of Shewanella putrefaciens on a mixed mineral phase

    NASA Astrophysics Data System (ADS)

    Boyanov, M. I.; O'Loughlin, E. J.; Kemner, K. M.

    2009-11-01

    The initial Fe(III) minerals and the secondary mineralization products of Shewanella putrefaciens CN32 grown in the presence of dissolved phosphate and a commercial Fe(III) oxide, nominally nanoparticulate lepidocrocite, were determined using XRD and XAFS. The starting material was transformed by the bacteria from a reddish brown, rust colour mineral to a dark green phase over 90 days. Acid extraction of the bioreduced solids with 0.75 M HCl recovered 83% of the total iron as Fe(II), leaving a solid, acid-resistant phase. The latter was identified as nanoparticulate hematite by EXAFS. Subsequently, the starting Fe(III) phase was determined to be a mixture of 60% lepidocrocite, 26% ferrihydrite, and 14% hematite, using linear combination EXAFS analysis. For the acid-extractable phase, XANES and EXAFS indicated a predominantly Fe(II) valence state and a spectrum consistent with a mixture of brucite-type minerals(e.g., green rust or ferrous hydroxide) and siderite. The observed transformations suggest that in this mixed-mineral system, lepidocrocite and ferrihydrite are readily reducible to green rust and siderite, whereas hematite is less amenable to bacterial reduction. This study also demonstrates the utility of XAFS spectroscopy in the quantitative characterization of dissimilatory metal transformations, particularly in complex systems such as nanoparticulate minerals in hydrated mineral-bacteria assemblages.

  16. Validation of keratan sulfate level in mucopolysaccharidosis type IVA by liquid chromatography-tandem mass spectrometry.

    PubMed

    Tomatsu, Shunji; Montaño, Adriana M; Oguma, Toshihiro; Dung, Vu Chi; Oikawa, Hirotaka; de Carvalho, Talita Giacomet; Gutiérrez, María L; Yamaguchi, Seiji; Suzuki, Yasuyuki; Fukushi, Masaru; Kida, Kazuhiro; Kubota, Mitsuru; Barrera, Luis; Orii, Tadao

    2010-12-01

    Mucopolysaccharidosis type IVA (MPS IVA, Morquio A disease), a progressive lysosomal storage disease, causes skeletal chondrodysplasia through excessive storage of keratan sulfate (KS). KS is synthesized mainly in cartilage and released to the circulation. The excess storage of KS disrupts cartilage, consequently releasing more KS into circulation, which is a critical biomarker for MPS IVA. Thus, assessment of KS level provides a potential screening strategy and determines clinical course and efficacy of therapies. We have recently developed a tandem mass spectrometry liquid chromatography [LC/MS/MS] method to assay KS levels in blood. Forty-nine blood specimens from patients with MPS IVA [severe (n = 33), attenuated (n = 11) and undefined (n = 5)] were analyzed for comparison of blood KS concentration with that of healthy subjects and for correlation with clinical severity. Plasma samples were digested by keratanase II to obtain disaccharides of KS. Digested samples were assayed by LC/MS/MS. We found that blood KS levels (0.4-26 µg/ml) in MPS IVA patients were significantly higher than those in age-matched controls (0.67-4.6 µg/ml; P < 0.0001). It was found that blood KS level varied with age and clinical severity in the patients. Blood KS levels in MPS IVA peaked between 2 years and 5 years of age (mean 11.4 µg/ml). Blood KS levels in severe MPS IVA (mean 7.3 µg/ml) were higher than in the attenuated form (mean 2.1 µg/ml) (P = 0.012). We also found elevated blood KS levels in other types of MPS. These findings indicate that the new KS assay for blood is suitable for early diagnosis and longitudinal assessment of disease severity in MPS IVA.

  17. The prognostic value of rectal invasion for stage IVA uterine cervical cancer treated with radiation therapy.

    PubMed

    Wakatsuki, Masaru; Kato, Shingo; Kiyohara, Hiroki; Ohno, Tatsuya; Karasawa, Kumiko; Tamaki, Tomoaki; Ando, Ken; Shiba, Shintaro; Kamada, Tadashi; Nakano, Takashi

    2016-03-23

    The prognostic value of rectal invasion is still unclear in stage IVA cervical cancer. The objective of this study is to evaluate patient outcome and prognostic factors in stage IVA cervical cancer treated with radiation therapy. A retrospective review of the medical records of patients treated with definitive photon radiation therapy for pathologically proven stage IVA cervical cancer between 1980 and 2010 was performed. Eligible patients for the present study were diagnosed with clinical stage IVA cervical cancer by cystoscopy or/and proctoscopy, and they received definitive radiation therapy consisting of a combination of external beam radiotherapy and high-dose-rate brachytherapy. All patients underwent CT scans of the abdomen and pelvis. Among the 67 stage IVA patients studied, 53 patients were stage IVA on the basis of bladder invasion, 7 according to rectal mucosal invasion, and 7 because of both bladder and rectal mucosal invasion. Median follow-up of all patients and surviving patients was 19 months (range, 2-235 months) and 114 months (range, 14-223 months), respectively. The 5-year local control (LC), disease-free survival (DFS), and overall survival (OS) rate were 55, 17, and 24%, respectively. Rectal invasion had significant impact on DFS, but bladder invasion had the opposite effect (p = 0.00006 and 0.005, respectively). There were significant differences of LC, DFS and OS rates between patients with and without rectal invasion (p = 0.006, 0.00006 and 0.05, respectively). Patients with stage IVA cervical cancer had poor prognosis, with 5-year survival of only 24%. Furthermore, in stage IVA, rectal invasion might be a worse prognostic factor than bladder invasion.

  18. Predicting genetic traits and epitope analysis of apxIVA in Actinobacillus pleuropneumoniae.

    PubMed

    Shin, Min-Kyoung; Cha, Seung-Bin; Lee, Won-Jung; Yoo, Han Sang

    2011-06-01

    Actinobacillus pleuropneumoniae causes a severe hemorrhagic pneumonia in pigs. Fifteen serotypes of A. pleuropneumoniae express four different Apx toxins that belong to the pore-forming repeats-in-toxin (RTX) group of toxins. ApxIV, which is conserved and up-regulated in vivo, could be an excellent candidate for the development of a protective cross-serotype immunity vaccine, and could aid in the differential diagnosis of diseases caused by A. pleuropneumoniae. We identified and sequenced apxIVA from A. pleuropneumoniae serotype 2 isolated in Korea (Kor-ApxIVA). The Kor-ApxIVA was closely related to Switzerland (AF021919), China (CP000687), and China (GQ332268), showing 98.6%, 98.4%, and 97.2% amino acid homology, respectively. The level of amino acid homology, however, was higher than the nucleotide homology. The structural characteristics of ApxIVA showed RTX proteins, including N-terminal hydrophobic domains, signature sequences for potential acylation sites, and repeated glycine-rich nonapeptides in the C-terminal region of the protein. Thirty glycine-rich nonapeptides with the consensus sequence, L/V-X-G-G-X-G-N/D-D-X, were found in the C-terminus of the Kor-ApxIVA. In addition, the Kor-ApxIVA was predicted for the linear B-cell epitopes and conserved domains with determined peptide sequences. This genetic analysis of the Kor-ApxIVA might be an important foundation for future biological and functional research on ApxIVA.

  19. How the Inductive Voltage Adder (IVA) output impedance affects impedance dynamics of a Self-Magnetic Pinch (SMP) diode

    NASA Astrophysics Data System (ADS)

    Renk, Timothy; Simpson, Sean; Webb, Timothy; Mazarakis, Michael; Kiefer, Mark

    2016-10-01

    The SMP diode, fielded on the RITS-6 (3.5-8.5 MV) IVA accelerator at Sandia National Laboratories, produces a focused electron beam (<3mm diameter) onto a high Z metal converter for flash x-ray applications. Experiments have been undertaken with two different magnetically insulated transmission line (MITL) center conductors, of 40 and 80 ohms flow impedance. We have operated in-situ heating and discharge-cleaning hardware in the load region, in order to address the tendency of some shots to undergo premature impedance (Z) collapse, defined as a fall in impedance beyond that due to normal movement of electrode plasmas that reduces the effective A-K gap. The goal of heating/cleaning was to reduce the volume of evolving gases near the A-K gap. Despite clear evidence that the cleaning techniques removed the proton portion of beam current, we observed no consistent increase in diode impedance (ZDIODE). This forced an examination of the role that the IVA flow impedance has on ZDIODE. A preliminary conclusion is that ZDIODE should be at least 1.5 times the flow impedance before ZDIODE is a parameter independent of flow impedance. This has implications for SMP as a load for a IVA, since ZDIODE >100 ohms has not been consistently demonstrated. Data analysis is ongoing, and latest results will be reported. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  20. Glass phase and other multiple liquid-to-liquid transitions resulting from two-liquid phase competition

    NASA Astrophysics Data System (ADS)

    Tournier, Robert F.

    2016-11-01

    Melt supercooling leads to glass formation. Liquid-to-liquid phase transitions are observed depending on thermal paths. Viscosity, density and surface tension thermal dependences measured at heating and subsequent cooling show hysteresis below a branching temperature and result from the competition of two-liquid phases separated by an enthalpy difference depending on temperature. The nucleation classical equation of these phases is completed by this enthalpy saving existing at all temperatures. The glass phase thermodynamic parameters and their thermal variation have already been determined in such a two-liquid model. They are used at high temperatures to predict liquid-to-liquid transitions in some metallic glass-forming melts.

  1. Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

    PubMed

    Solanki, Guirish A; Martin, Kenneth W; Theroux, Mary C; Lampe, Christina; White, Klane K; Shediac, Renée; Lampe, Christian G; Beck, Michael; Mackenzie, William G; Hendriksz, Christian J; Harmatz, Paul R

    2013-03-01

    Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed.

  2. Mucopolysaccharidosis type IVA (Morquio A disease): clinical review and current treatment.

    PubMed

    Tomatsu, S; Montaño, A M; Oikawa, H; Smith, M; Barrera, L; Chinen, Y; Thacker, M M; Mackenzie, W G; Suzuki, Y; Orii, T

    2011-06-01

    Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio A, is a rare, autosomal recessive disorder caused by a deficiency of the lysosomal enzyme N-acetylgalatosamine-6-sulfate-sulfatase (GALNS), which catalyzes a step in the catabolism of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate (C6S). It leads to accumulation of the KS and C6S, mainly in bone and cornea, causing a systemic skeletal chondrodysplasia. MPS IVA has a variable age of onset and variable rate of progression. Common presenting features include elevation of urinary and blood KS, marked short stature, hypoplasia of the odontoid process, pectus carinatum, kyphoscoliosis, genu valgum, laxity of joints and corneal clouding; however there is no central nervous system impairment. Generally, MPS IVA patients with a severe form do not survive beyond the third decade of life whereas those patients with an attenuated form may survive over 70 years. There has been no effective therapy for MPS IVA, and care has been palliative. Enzyme replacement therapy (ERT) and hematopoietic stem cell therapy (HSCT) have emerged as a treatment for mucopolysaccharidoses disorders, including Morquio A disease. This review provides an overview of the clinical manifestations, diagnosis and symptomatic management of patients with MPS IVA and describes potential perspectives of ERT and HSCT. The issue of treating very young patients is also discussed.

  3. Detecting Symptom Exaggeration in College Students Seeking ADHD Treatment: Performance Validity Assessment Using the NV-MSVT and IVA-Plus.

    PubMed

    Leppma, Monica; Long, Daniel; Smith, Megan; Lassiter, Candace

    2017-01-27

    The symptoms of ADHD are highly subjective, and there is ample empirical evidence that demonstrates the ease with which impairments in attention can be feigned on many commonly used subjective and objective measures of attention. We examined the combination of two assessment measures, NV-MSVT and IVA+, to screen for performance validity and ADHD symptoms in college students. Results indicated that the NV-MSVT was effective in differentiating between students with potential high impairment, such as ADHD, and possible malingerers. In addition, in vivo clinical data (N = 350) resulted in lower validity cut-off scores on the IVA+ than had been previously suggested. Clinical implications and future research are also discussed.

  4. Discrimination of Spore-Forming Bacilli Using spoIVA

    NASA Technical Reports Server (NTRS)

    Venkateswaran, Kasthuri; LaDuc, Myron; Stuecker, Tara

    2009-01-01

    A method of discriminating between spore-forming and non-spore-forming bacteria is based on a combination of simultaneous sporulation-specific and non-sporulation-specific quantitative polymerase chain reactions (Q-PCRs). The method was invented partly in response to the observation that for the purposes of preventing or reducing biological contamination affecting many human endeavors, ultimately, only the spore-forming portions of bacterial populations are the ones that are problematic (or, at least, more problematic than are the non-spore-forming portions). In some environments, spore-forming bacteria constitute small fractions of the total bacterial populations. The use of sporulation-specific primers in Q-PCR affords the ability to assess the spore-forming fraction of a bacterial population present in an environment of interest. This assessment can provide a more thorough and accurate understanding of the bacterial contamination in the environment, thereby making it possible to focus contamination- testing, contamination-prevention, sterilization, and decontamination resources more economically and efficiently. The method includes the use of sporulation-specific primers in the form of designed, optimized deoxyribonucleic acid (DNA) oligonucleotides specific for the bacterial spoIVA gene (see table). [In "spoIVA," "IV" signifies Roman numeral four and the entire quoted name refers to gene A for the fourth stage of sporulation.] These primers are mixed into a PCR cocktail with a given sample of bacterial cells. A control PCR cocktail into which are mixed universal 16S rRNA primers is also prepared. ["16S rRNA" denotes a ribosomal ribonucleic acid (rRNA) sequence that is common to all organisms.] Following several cycles of heating and cooling according to the PCR protocol to amplify amounts of DNA molecules, the amplification products can be analyzed to determine the types of bacterial cells present within the samples. If the amplification product is strong

  5. Group IVA phospholipase A(2) deficiency prevents CCl4-induced hepatic cell death through the enhancement of autophagy.

    PubMed

    Ishihara, Keiichi; Kanai, Shiho; Tanaka, Kikuko; Kawashita, Eri; Akiba, Satoshi

    2016-02-26

    Group IVA phospholipase A2 (IVA-PLA2), which generates arachidonate, plays a role in inflammation. IVA-PLA2-deficiency reduced hepatotoxicity and hepatocyte cell death in mice that received a single dose of carbon tetrachloride (CCl4) without any inhibitory effects on CCl4-induced lipid peroxidation. An immunoblot analysis of extracts from wild-type mouse- and IVA-PLA2 KO mouse-derived primary hepatocytes that transiently expressed microtubule-associated protein 1 light chain 3B (LC3) revealed a higher amount of LC3-II, a typical index of autophagosome formation, in IVA-PLA2-deficient cells, suggesting the enhancement of constitutive autophagy. IVA-PLA2 may promote CCl4-induced cell death through the suppression of constitutive autophagy in hepatocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Amino acid sequence of bovine gamma E (IVa) lens crystallin.

    PubMed Central

    Kilby, G. W.; Sheil, M. M.; Shaw, D.; Harding, J. J.; Truscott, R. J.

    1997-01-01

    When electrospray ionization mass spectrometry (ESMS) was used to analyze purified bovine gamma E (gamma IVa)-crystallin, it yielded a relative molecular mass (M(r)) of 20.955 +/- 5. This mass is significantly different from that calculated from the published sequence (M(r) 20.894) (White HE et al., 1989, J Mol Biol 207:217-235). Further, ES-MS analysis of the protein after it had been reduced and carboxymethylated indicated the presence of five cysteine residues, whereas the published sequence contains six (Kilby GW et al., 1995, Eur Mass Spectrom 1:203-208). The entire protein sequence of gamma E crystallin has therefore been studied via a combination of ES-MS, ES-MS/MS, and Edman amino acid sequencing. The corrected sequence gives an M(r) of 20.955.3, which matches that obtained by ES-MS analysis of the purified native protein. The corrected sequence is also in agreement with a recent cDNA sequence obtained for a bovine gamma-crystallin by R. Hay (pers. comm.). PMID:9098901

  7. Amino acid sequence of bovine gamma E (IVa) lens crystallin.

    PubMed

    Kilby, G W; Sheil, M M; Shaw, D; Harding, J J; Truscott, R J

    1997-04-01

    When electrospray ionization mass spectrometry (ESMS) was used to analyze purified bovine gamma E (gamma IVa)-crystallin, it yielded a relative molecular mass (M(r)) of 20.955 +/- 5. This mass is significantly different from that calculated from the published sequence (M(r) 20.894) (White HE et al., 1989, J Mol Biol 207:217-235). Further, ES-MS analysis of the protein after it had been reduced and carboxymethylated indicated the presence of five cysteine residues, whereas the published sequence contains six (Kilby GW et al., 1995, Eur Mass Spectrom 1:203-208). The entire protein sequence of gamma E crystallin has therefore been studied via a combination of ES-MS, ES-MS/MS, and Edman amino acid sequencing. The corrected sequence gives an M(r) of 20.955.3, which matches that obtained by ES-MS analysis of the purified native protein. The corrected sequence is also in agreement with a recent cDNA sequence obtained for a bovine gamma-crystallin by R. Hay (pers. comm.).

  8. Di-sulfated Keratan Sulfate as a Novel Biomarker for Mucopolysaccharidosis II, IVA, and IVB.

    PubMed

    Shimada, Tsutomu; Tomatsu, Shunji; Mason, Robert W; Yasuda, Eriko; Mackenzie, William G; Hossain, Jobayer; Shibata, Yuniko; Montaño, Adriana M; Kubaski, Francyne; Giugliani, Roberto; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Kenji E; Fukao, Toshiyuki; Orii, Tadao

    2015-01-01

    Keratan sulfate (KS) is a storage material in mucopolysaccharidosis IV (MPS IV). However, no detailed analysis has been reported on subclasses of KS: mono-sulfated KS and di-sulfated KS. We established a novel method to distinguish and quantify mono- and di-sulfated KS using liquid chromatography-tandem mass spectrometry and measured both KS levels in various specimens.Di-sulfated KS was dominant in shark cartilage and rat serum, while mono-sulfated KS was dominant in bovine cornea and human serum. Levels of both mono- and di-sulfated KS varied with age in the blood and urine from control subjects and patients with MPS II and IVA. The mean levels of both forms of KS in the plasma/serum from patients with MPS II, IVA, and IVB were elevated compared with that in age-matched controls. Di-sulfated KS provided more significant difference between MPS IVA and the age-matched controls than mono-sulfated KS. The ratio of di-sulfated KS to total KS in plasma/serum increased with age in control subjects and patients with MPS II but was age independent in MPS IVA patients. Consequently, this ratio can discriminate younger MPS IVA patients from controls. Levels of mono- and di-sulfated KS in urine of MPS IVA and IVB patients were all higher than age-matched controls for all ages studied.In conclusion, the level of di-sulfated KS and its ratio to total KS can distinguish control subjects from patients with MPS II, IVA, and IVB, indicating that di-sulfated KS may be a novel biomarker for these disorders.

  9. Intensity-modulated radiotherapy for stage IVA/IVB nasopharyngeal carcinoma: clinical outcomes and patterns of failure in an endemic area in China.

    PubMed

    Zeng, Lei; Tian, Yun-Ming; Sun, Xue-Ming; Huang, Ying; Chen, Chun-Yan; Han, Fei; Liu, Shuai; Lan, Mei; Guan, Ying; Deng, Xiao-Wu; Lu, Tai-Xiang

    2014-10-01

    The purpose of this study was to analyze the mode of relapse patterns and survival of 209 patients with stage IVA and IVB nasopharyngeal carcinoma (NPC). A total of 209 patients who underwent magnetic resonance imaging (MRI) and were subsequently histologically diagnosed with nondisseminated stage IV NPC received intensity-modulated radiotherapy (IMRT) as their primary treatment and were included in this retrospective study. Median follow-up time was 65 months (range, 3-108 months). The 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates for patients with stage IVA and stage IVB NPC were 72.7 vs. 60.0 % (p = 0.319), 62.9 vs. 51.3 % (p = 0.070), 82.9 vs. 93.1 % (p = 0.070), 82.9 vs. 82.9 % (p = 0.897), 76.4 vs. 58.5 % (p = 0.003), respectively. Age older than 44 years was found to be a statistically significant adverse independent prognostic factor for OS. Patients with advanced N status had worse OS, DFS, and DMFS rates. Patients with a primary gross tumor volume (GTV-P) ≥ 55.11 ml had worse OS, DFS, and LRRFS rates. The results of treating stage IVA NPC with IMRT were excellent. Distant metastasis remains the most difficult treatment challenge for patients with stage IVA and IVB NPC, and more effective systemic chemotherapy should be explored.

  10. Structural Basis for Dual Nucleotide Selectivity of Aminoglycoside 2″-Phosphotransferase IVa Provides Insight on Determinants of Nucleotide Specificity of Aminoglycoside Kinases*♦

    PubMed Central

    Shi, Kun; Berghuis, Albert M.

    2012-01-01

    Enzymatic phosphorylation through a family of enzymes called aminoglycoside O-phosphotransferases (APHs) is a major mechanism by which bacteria confer resistance to aminoglycoside antibiotics. Members of the APH(2″) subfamily are of particular clinical interest because of their prevalence in pathogenic strains and their broad substrate spectra. APH(2″) enzymes display differential preferences between ATP or GTP as the phosphate donor, with aminoglycoside 2″-phosphotransferase IVa (APH(2″)-IVa) being a member that utilizes both nucleotides at comparable efficiencies. We report here four crystal structures of APH(2″)-IVa, two of the wild type enzyme and two of single amino acid mutants, each in complex with either adenosine or guanosine. Together, these structures afford a detailed look at the nucleoside-binding site architecture for this enzyme and reveal key elements that confer dual nucleotide specificity, including a solvent network in the interior of the nucleoside-binding pocket and the conformation of an interdomain linker loop. Steady state kinetic studies, as well as sequence and structural comparisons with members of the APH(2″) subfamily and other aminoglycoside kinases, rationalize the different substrate preferences for these enzymes. Finally, despite poor overall sequence similarity and structural homology, analysis of the nucleoside-binding pocket of APH(2″)-IVa shows a striking resemblance to that of eukaryotic casein kinase 2 (CK2), which also exhibits dual nucleotide specificity. These results, in complement with the multitude of existing inhibitors against CK2, can serve as a structural basis for the design of nucleotide-competitive inhibitors against clinically relevant APH enzymes. PMID:22371504

  11. Structural basis for dual nucleotide selectivity of aminoglycoside 2''-phosphotransferase IVa provides insight on determinants of nucleotide specificity of aminoglycoside kinases.

    PubMed

    Shi, Kun; Berghuis, Albert M

    2012-04-13

    Enzymatic phosphorylation through a family of enzymes called aminoglycoside O-phosphotransferases (APHs) is a major mechanism by which bacteria confer resistance to aminoglycoside antibiotics. Members of the APH(2″) subfamily are of particular clinical interest because of their prevalence in pathogenic strains and their broad substrate spectra. APH(2″) enzymes display differential preferences between ATP or GTP as the phosphate donor, with aminoglycoside 2″-phosphotransferase IVa (APH(2″)-IVa) being a member that utilizes both nucleotides at comparable efficiencies. We report here four crystal structures of APH(2″)-IVa, two of the wild type enzyme and two of single amino acid mutants, each in complex with either adenosine or guanosine. Together, these structures afford a detailed look at the nucleoside-binding site architecture for this enzyme and reveal key elements that confer dual nucleotide specificity, including a solvent network in the interior of the nucleoside-binding pocket and the conformation of an interdomain linker loop. Steady state kinetic studies, as well as sequence and structural comparisons with members of the APH(2″) subfamily and other aminoglycoside kinases, rationalize the different substrate preferences for these enzymes. Finally, despite poor overall sequence similarity and structural homology, analysis of the nucleoside-binding pocket of APH(2″)-IVa shows a striking resemblance to that of eukaryotic casein kinase 2 (CK2), which also exhibits dual nucleotide specificity. These results, in complement with the multitude of existing inhibitors against CK2, can serve as a structural basis for the design of nucleotide-competitive inhibitors against clinically relevant APH enzymes.

  12. Alleviation of high-fat diet-induced fatty liver damage in group IVA phospholipase A2-knockout mice.

    PubMed

    Ii, Hiromi; Yokoyama, Naoki; Yoshida, Shintaro; Tsutsumi, Kae; Hatakeyama, Shinji; Sato, Takashi; Ishihara, Keiichi; Akiba, Satoshi

    2009-12-01

    Hepatic fat deposition with hepatocellular damage, a feature of non-alcoholic fatty liver disease, is mediated by several putative factors including prostaglandins. In the present study, we examined whether group IVA phospholipase A(2) (IVA-PLA(2)), which catalyzes the first step in prostanoid biosynthesis, is involved in the development of fatty liver, using IVA-PLA(2)-knockout mice. Male wild-type mice on high-fat diets (20% fat and 1.25% cholesterol) developed hepatocellular vacuolation and liver hypertrophy with an increase in the serum levels of liver damage marker aminotransferases when compared with wild-type mice fed normal diets. These high-fat diet-induced alterations were markedly decreased in IVA-PLA(2)-knockout mice. Hepatic triacylglycerol content was lower in IVA-PLA(2)-knockout mice than in wild-type mice under normal dietary conditions. Although high-fat diets increased hepatic triacylglycerol content in both genotypes, the degree was lower in IVA-PLA(2)-knockout mice than in wild-type mice. Under the high-fat dietary conditions, IVA-PLA(2)-knockout mice had lower epididymal fat pad weight and smaller adipocytes than wild-type mice. The serum level of prostaglandin E(2), which has a fat storage effect, was lower in IVA-PLA(2)-knockout mice than in wild-type mice, irrespective of the kind of diet. In both genotypes, high-fat diets increased serum leptin levels equally between the two groups, but did not affect the serum levels of adiponectin, resistin, free fatty acid, triacylglycerol, glucose, or insulin. Our findings suggest that a deficiency of IVA-PLA(2) alleviates fatty liver damage caused by high-fat diets, probably because of the lower generation of IVA-PLA(2) metabolites, such as prostaglandin E(2). IVA-PLA(2) could be a promising therapeutic target for obesity-related diseases including non-alcoholic fatty liver disease.

  13. Molecular analysis of mucopolysaccharidosis IVA (Morquio A) in Spain.

    PubMed

    Pajares, Sonia; Alcalde, Carlos; Couce, Ma Luz; Del Toro, Mireia; González-Meneses, Antonio; Guillén, Encarna; Pineda, Mercè; Pintos, Guillem; Gort, Laura; Coll, Ma José

    2012-06-01

    Mucopolysaccharidosis type IVA (Morquio A) is an inherited metabolic disease with autosomal recessive inheritance. The pathology is due to a deficient activity of N-acetylgalactosamine-6-sulfate-sulfatase, which is involved in the degradation of keratan sulfate and chondroitin-6-sulfate. To date more than 150 mutations have been described in the GALNS gene in different populations. The aim of this study was to analyze the mutations and polymorphisms in Spain in order to know the epidemiology of our population and also to offer genetic counseling to affected families. We found 30 mutant alleles in the 15 families analyzed completing all the genotypes. Most of the mutations that we found were missense mutations, six of which were novel: p.S74F, p.E121D, p.Y254C, p.E260K, p.T394P and p.N495Y; we also found a small deletion (c.1142delC) and a probable deep intronic mutation that causes the loss of exon 5 (c.423_566del) found in cDNA. Both mutations are described in this study for the first time. We also identified 20 polymorphisms previously reported and 2 novel ones: (c.633+222T/C and c.898+25C>G). In conclusion, we have identified the mutations responsible for Mucopolysaccharidosis IV A in Spain. We found great allelic heterogeneity, as occurs in other populations, which hinders the establishment of genotype-phenotype correlations in Spain. This study has been very useful for genetic counseling to the affected families.

  14. Appendix to the report from the low-residue soldering task force: Phase 2 results

    SciTech Connect

    Iman, R.L.; Anderson, D.J.; Huffman, D.D.

    1995-12-01

    The LRSTF report for Phase I of its evaluation of low-residue soldering was issued in June 1995. This Appendix summarizes the results of follow-on testing performed in Phase II and compares electrical test results for both phases. Deliberate decisions were made by the LRSTF in Phase I to challenge the design guideline limits in MILSTD-275, Printed Wiring for Electronic Equipment The LRSTF considered this approach to produce a ``worst case`` design and provide useful information about the robustness of LR soldering processes. As such, good design practices were sometimes deliberately violated in designing the LRSTF board. This approach created some anomalies for both LR boards and RMA/cleaned controls. Phase II testing verified that problems that affected both RMA/cleaned and LR boards in Phase I were design related.

  15. Observation results of actual phase defects using micro coherent EUV scatterometry microscope

    NASA Astrophysics Data System (ADS)

    Hashimoto, Hiraku; Harada, Tetsuo; Watanabe, Takeo

    2016-10-01

    One of the critical issue of EUV lithography is fabrication of defect-free mask. The origin of the defect is a particle inside the multilayer and bump or pit on glass substrate. This type of defect is called a phase defect. If there is a phase defect, the reflection phase is disordered. As a result, the phase structure is printed as a defect on a wafer. Thus, we have developed micro coherent EUV scatterometry microscope (we called micro-CSM) for phase defect characterization. Micro-CSM records scattering signal from a defect directly exposed by focused coherent EUV having a spot size of φ140-nm in diameter. An off-axis-type Fresnel zone plate was employed as a focusing optics. Phase distribution of the defect is reconstructed with the scattering image by the coherent-diffraction-imaging method. We observed actual phase defects in this work. Actual phase defects were on a mask blanks which was the same grade of the pre-production mask of the semiconductor devices. The positions of actual phase defects have been already inspected by the actinic blank inspection tool. And, the actual phase defects have been already observed using an atomic force microscope. A purpose of this work is observation of these actual defects using micro-CSM and comparison of the results.

  16. Prognostic significance of tumour progression and human papillomavirus in advanced tonsillar cancer classified as stage IVa.

    PubMed

    Park, E; Jung, K-Y; Kwon, S-Y; Woo, J-S; Cho, J-G; Park, M W; Kim, I S; Kim, S J; Baek, S-K

    2015-01-01

    To identify clinical factors that can explain the differences in treatment outcome, and examine the value of human papillomavirus infection as a prognostic biomarker in stage IVa tonsillar carcinomas. Fifty-nine patients with tonsillar carcinoma classified as stage IVa were retrospectively analysed for survival outcomes according to various clinical factors. Human papillomavirus infection was evaluated using a human papillomavirus DNA chip test and immunohistochemical staining for p16 and p53. Lower disease-free survival rates were associated with increasing local invasiveness and nodal status. Although human papillomavirus positivity and p16 expression was more common in locally advanced tonsillar carcinomas with advanced nodal status, the overall survival rate was better for patients with human papillomavirus positive, p16-positive tumours. The disease-free survival rate may differ according to local tumour invasiveness and nodal status, even for stage IVa tonsillar cancers. Human papillomavirus infection may be a useful biomarker for predicting treatment outcomes for stage VIa tumours.

  17. The impact of an IVA robot on the Space Station microgravity environment

    NASA Technical Reports Server (NTRS)

    Harman, Phillip E.; Rohn, Douglas A.

    1989-01-01

    In order to maintain a microgravity environment during Space Station operations, it will be necessary to minimize reaction forces. These mechanical forces will typically occur during reboost, docking, equipment operation, intravehicular activities (IVA) robot operation, or crew activity. This paper focuses on those disturbances created by an IVA robot and its impact on the Space Station microgravity environment. The robot dynamic analysis that was used to generate the forcing function as the input into a finite element model of the U.S. Laboratory will be shown. Acceleration levels were determined through analysis and have shown that a robotic system can sustain reaction forces into the station below 0.0001 g. A comparison between IVA robot effects and crew motion effects on the low-g environment is also described. It is concluded that robot trajectory shaping and motor accelerations feedback can minimize reaction forces.

  18. The impact of an IVA robot on the Space Station microgravity environment

    NASA Technical Reports Server (NTRS)

    Harman, Phillip E.; Rohn, Douglas A.

    1989-01-01

    In order to maintain a microgravity environment during Space Station operations, it will be necessary to minimize reaction forces. These mechanical forces will typically occur during reboost, docking, equipment operation, intravehicular activities (IVA) robot operation, or crew activity. This paper focuses on those disturbances created by an IVA robot and its impact on the Space Station microgravity environment. The robot dynamic analysis that was used to generate the forcing function as the input into a finite element model of the U.S. Laboratory will be shown. Acceleration levels were determined through analysis and have shown that a robotic system can sustain reaction forces into the station below 0.0001 g. A comparison between IVA robot effects and crew motion effects on the low-g environment is also described. It is concluded that robot trajectory shaping and motor accelerations feedback can minimize reaction forces.

  19. IVA the robot: Design guidelines and lessons learned from the first space station laboratory manipulation system

    NASA Technical Reports Server (NTRS)

    Konkel, Carl R.; Powers, Allen K.; Dewitt, J. Russell

    1991-01-01

    The first interactive Space Station Freedom (SSF) lab robot exhibit was installed at the Space and Rocket Center in Huntsville, AL, and has been running daily since. IntraVehicular Activity (IVA) the robot is mounted in a full scale U.S. Lab (USL) mockup to educate the public on possible automation and robotic applications aboard the SSF. Responding to audio and video instructions at the Command Console, exhibit patrons may prompt IVA to perform a housekeeping task or give a speaking tour of the module. Other exemplary space station tasks are simulated and the public can even challenge IVA to a game of tic tac toe. In anticipation of such a system being built for the Space Station, a discussion is provided of the approach taken, along with suggestions for applicability to the Space Station Environment.

  20. Chemoradiation With Concomitant Boosts Followed by Radical Surgery in Locally Advanced Cervical Cancer: Long-term Results of the ROMA-2 Prospective Phase 2 Study

    SciTech Connect

    Ferrandina, Gabriella; Gambacorta, Antonietta; Gallotta, Valerio; Smaniotto, Daniela; Fagotti, Anna; Tagliaferri, Luca; Foti, Elvira; Fanfani, Francesco; Autorino, Rosa; Scambia, Giovanni; Valentini, Vincenzo

    2014-11-15

    Purpose: This prospective, phase 2 study aimed at assessing the efficacy of accelerated fractionation radiation therapy by concomitant boosts (CBs) associated with chemoradiation therapy (CRT) of the whole pelvis, in improving the rate of pathological complete response (pCR) to treatment in patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2-IVA locally advanced cervical cancer. Methods and Materials: Neoadjuvant CRT included conformal irradiation of the whole pelvis with a total dose of 39.6 Gy (1.8 cGy/fraction, 22 fractions), plus additional irradiation of primary tumor and parametria with 10.8 Gy administered with CBs (0.9 cGy/fraction, 12 fractions, every other day). Concomitant chemotherapy included cisplatin (20 mg/m{sup 2}, days 1-4 and 26-30 of treatment), and capecitabine (1300 mg/m{sup 2}/daily, orally) during the first 2 and the last 2 weeks of treatment. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 6 to 8 weeks from CRT. Toxicity was recorded according to Radiation Therapy Oncology Group toxicity criteria and Chassagne grading system. Based on the Simon design, 103 cases were required, and the regimen would be considered active if >45 pCR were registered (α error = 0.05; β error = 0.1). Results: pCR was documented in 51 cases (50.5%), and the regimen was considered active, according to the planned statistical assumptions. At median follow-up of 36 months (range: 7-85 months), the 3-year local failure rate was 7%, whereas the 3-year disease-free and overall survival rates were 73.0% and 86.1%, respectively. Grade 3 leukopenia and neutropenia were reported in only 1 and 2 cases, respectively. Gastrointestinal toxicity was always grade 1 or 2. Conclusions: Addition of CBs in the accelerated fractionation modality to the whole pelvis chemoradiation followed by radical surgery results in a high rate of pathologically assessed complete response to CRT and a very

  1. Exact result on topology and phase transitions at any finite N.

    PubMed

    Casetti, Lapo; Cohen, E G D; Pettini, Marco

    2002-03-01

    We study analytically the topology of a family of submanifolds of the configuration space of the mean-field XY model, computing also a topological invariant (the Euler characteristic). We prove that a particular topological change of these submanifolds is connected to the phase transition of this system, and exists also at finite N. The present result is the first analytic proof that a phase transition has a topological origin and provides a key to a possible better understanding of the origin of phase transitions at their deepest level, as well as to a possible definition of phase transitions at finite N.

  2. In vitro effect of genistein on DNA damage in leukocytes from mucopolysaccharidosis IVA patients.

    PubMed

    Negretto, G W; Deon, M; Burin, M; Biancini, G B; Ribas, G; Garcia, S C; Goethel, G; Fracasso, R; Giugliani, L; Giugliani, R; Vargas, C R

    2014-02-01

    Mucopolysaccharidosis IVA is a lysosomal storage disorder leading to an increase in glycosaminoglycans storage. Genistein is an isoflavone capable to inhibit glycosaminoglycans production. The objective of this study was to analyze the in vitro effect of different concentrations of genistein on DNA injury in mucopolysaccharidosis IVA patients. The lower concentration tested (10 μM) showed a significant increase on DNA injury in vitro, although higher concentrations (30 μM and 50 μM) showed higher DNA damage. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Septal membrane localization by C-terminal amphipathic α-helices of MinD in Bacillus subtilis mutant cells lacking MinJ or DivIVA.

    PubMed

    Ishikawa, Kazuki; Matsuoka, Satoshi; Hara, Hiroshi; Matsumoto, Kouji

    2017-06-30

    The Min system, which inhibits assembly of the cytokinetic protein FtsZ, is largely responsible for positioning the division site in rod-shaped bacteria. It has been reported that MinJ, which bridges DivIVA and MinD, is targeted to the cell poles by an interaction with DivIVA, and that MinJ in turn recruits MinCD to the cell poles. MinC, however, is located primarily at active division sites at the mid-cell when expressed from its native promoter. Surprisingly, we found that B. subtilis MinD is located at nascent septal membranes and at an asymmetric site on lateral membranes between nascent septal membranes in filamentous cells lacking MinJ or DivIVA. B. subtilis MinD has two amphipathic α-helices rich in basic amino acid residues at its C-terminus; one of these, named MTS1 here, is the counterpart of the membrane targeting sequence (MTS) in Escherichia coli MinD while the other, named MTS-like sequence (MTSL), is the nearest helix to MTS1. These amphipathic helices were located independently at nascent septal membranes in cells lacking MinJ or DivIVA, whereas elimination of the helices from the wild type protein reduced its localization considerably. MinD variants with altered MTS1 and MTSL, in which basic amino acid residues were replaced with proline or acidic residues, were not located at nascent septal membranes, indicating that the binding to the nascent septal membranes requires basic residues and a helical structure. The septal localization of MTSL, but not of MTS1, was dependent on host cell MinD. These results suggest that MinD is targeted to nascent septal membranes via its C-terminal amphipathic α-helices in B. subtilis cells lacking MinJ or DivIVA. Moreover, the diffuse distribution of MinD lacking both MTSs suggests that only a small fraction of MinD depends on MinJ for its localization to nascent septal membranes.

  4. Performance results of a 300-degree linear phase modulator for spaceborne communications applications

    NASA Technical Reports Server (NTRS)

    Mysoor, N. R.; Mueller, R. O.

    1993-01-01

    A phase modulator capable of large linear phase deviation, low loss, and wide band operation with good thermal stability was developed for deep space spacecraft transponder (DST) applications at X-band (8.415 GHz) and Ka-band (32 GHz) downlinks. The design uses a two-stage circulator-coupled reflection phase shifter with constant gamma hyperabrupt varactors and an efficient modulator driver circuit to obtain a phase deviation of +/-2.5 rad with better than 8 percent linearity. The measured insertion loss is 6.6 dB +/- 0.35 dB at 8415 MHz. Measured carrier and relative sideband amplitudes resulting from phase modulation by sine wave and square modulating functions agree well with the predicted results.

  5. Performance results of a 300-deg linear phase modulator for spaceborne communications applications

    NASA Technical Reports Server (NTRS)

    Mysoor, Narayan R.; Mueller, Robert O.

    1993-01-01

    A phase modulator capable of large linear phase deviation, low loss, and wide band operation with good thermal stability was developed for deep space spacecraft transponder (DST) applications at X-band (8.415 GHz) and Ka-band (32 GHz) downlinks. The design uses a two-stage circulator-coupled reflection phase shifter with constant gamma hyperabrupt varactors and an efficient modulator driver circuit to obtain a phase deviation of +/- 2.5 rad with better than 8 percent linearity. The measured insertion loss is 6.6 dB +/- 0.35 dB at 8415 MHz. Measured carrier and relative sideband amplitudes resulting from phase modulation by sine wave and square modulating functions agree well with the predicted results.

  6. Loss of Brap Results in Premature G1/S Phase Transition and Impeded Neural Progenitor Differentiation.

    PubMed

    Lanctot, Alison A; Guo, Yan; Le, Yicong; Edens, Brittany M; Nowakowski, Richard S; Feng, Yuanyi

    2017-08-01

    Cells initiate fate decisions during G1 phase by converting extracellular signals into distinctive cell cycle kinetics. The DNA replication timing is determined in G1 phase; lengthened G1 and hastened S phases correlate with increased neurogenic propensity of neural progenitor cells (NPCs), although the underlying molecular control remains elusive. Here, we report that proper G1 phase completion in NPCs requires Brap, a Ras-Erk signaling modulator with ubiquitin E3 ligase activity. We identified Skp2 and Skp2-associated SCF ubiquitin ligase as a key target of Brap-mediated polyubiquitination. Loss of Brap resulted in elevated Skp2, which increased p27(Kip1) destruction, leading to G1 phase truncation and premature S phase entry. The aberrantly executed G1 in Brap-mutant NPCs, followed by hindered S phase progression and increased G2 phase arrest, which together prolonged the cell cycle, impeded neuronal differentiation and culminated in microcephaly. These findings demonstrate that neuronal differentiation is potentiated during G1 phase by Brap-directed cascade of events in cell signaling and protein turnover. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. 30 CFR 203.30 - Which leases are eligible for royalty relief as a result of drilling a phase 2 or phase 3 ultra...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... a result of drilling a phase 2 or phase 3 ultra-deep well? 203.30 Section 203.30 Mineral Resources... for Drilling Ultra-Deep Wells on Leases Not Subject to Deep Water Royalty Relief § 203.30 Which leases are eligible for royalty relief as a result of drilling a phase 2 or phase 3 ultra-deep well?...

  8. The Cu-Sn phase diagram, Part I: New experimental results.

    PubMed

    Fürtauer, S; Li, D; Cupid, D; Flandorfer, H

    2013-03-01

    Phase diagram investigation of the Cu-Sn system was carried out on twenty Cu-rich samples by thermal analysis (DTA), metallographic methods (EPMA/SEM-EDX) and crystallographic analysis (powder XRD, high temperature powder XRD). One main issue in this work was to investigate the high temperature phases beta (W-type) and gamma (BiF3-type) and to check the phase relations between them. In the high temperature powder XRD experiments the presence of the two-phase-field between the beta- and the gamma-phase could not be confirmed. Detailed study of primary literature together with our experimental results leads to a new phase diagram version with a higher order transformation between these two high temperature phases. The present work is designated as part I of our joint publication. The new findings described here have been included into a completely new thermodynamic assessment of the Cu-Sn phase diagram which is presented in part II.

  9. Measurement of Elevated Concentrations of Urine Keratan Sulfate by UPLC-MSMS in Lysosomal Storage Disorders (LSDs): Comparison of Urine Keratan Sulfate Levels in MPS IVA Versus Other LSDs.

    PubMed

    Ellsworth, Katarzyna A; Pollard, Laura M; Cathey, Sara; Wood, Tim

    2017-01-01

    Keratan sulfate (KS) is commonly elevated in urine samples from patients with mucopolysaccharidosis type IVA (MPS IVA) and is considered pathognomonic for the condition. Recently, a new method has been described by Martell et al. to detect and measure urinary KS utilizing LC-MS/MS. As a part of the validation of this method in our laboratory, we studied the sensitivity and specificity of elevated urine KS levels using 25 samples from 15 MPS IVA patients, and 138 samples from 102 patients with other lysosomal storage disorders, including MPS I (n = 9), MPS II (n = 13), MPS III (n = 23), MPS VI (n = 7), beta-galactosidase deficiency (n = 7), mucolipidosis (ML) type II, II/III and III (n = 51), alpha-mannosidosis (n = 11), fucosidosis (n = 4), sialidosis (n = 5), Pompe disease (n = 3), aspartylglucosaminuria (n = 4), and galactosialidosis (n = 1). As expected, urine KS values were significantly higher (fivefold average increase) than age-matched controls in all MPS IVA patients. Urine KS levels were also significantly elevated (threefold to fourfold increase) in patients with GM-1 gangliosidosis, MPS IVB, ML II and ML II/III, and fucosidosis. Urine KS was also elevated to a smaller degree (1.1-fold to 1.7-fold average increase) in patients with MPS I, MPS II, and ML III. These findings suggest that while the UPLC-MS/MS urine KS method is 100% sensitive for the detection of patients with MPS IVA, elevated urine KS is not specific for this condition. Therefore, caution is advised when interpreting urinary keratan sulfate results.

  10. Development of a monoclonal antibody against viral haemorrhagic septicaemia virus (VHSV) genotype IVa.

    PubMed

    Ito, T; Olesen, N J; Skall, H F; Sano, M; Kurita, J; Nakajima, K; Iida, T

    2010-02-24

    The viral haemorrhagic septicaemia virus (VHSV) comprises 4 major genotypes and a number of subtypes with, in most cases, distinct geographical distribution. A quick and simple detection method that can discriminate the different genotypes is desirable for a quick and more efficient prevention of the spread of genotypes to new geographical areas. A monoclonal antibody (MAb) against VHSV genotype IVa was produced, with the aim of providing a simple method of discriminating this genotype from the other VHSV genotypes (I, II, III and IVb). Balb/c mice were injected with purified VHSV-JF00Ehil (genotype IVa) from diseased farmed Japanese flounder. Ten hybridoma clones secreting monoclonal antibodies (MAbs) against VHSV were established. One of these, MAb VHS-10, reacted only with genotype IVa in indirect fluorescent antibody technique (IFAT) and ELISA. Using cell cultures that were transfected with each of the viral protein genes, it was shown that the MAb VHS-10 recognizes a nonlinear genotype IVa-specific epitope on the VHSV N-protein.

  11. Asymmetric division and differential gene expression during a bacterial developmental program requires DivIVA.

    PubMed

    Eswaramoorthy, Prahathees; Winter, Peter W; Wawrzusin, Peter; York, Andrew G; Shroff, Hari; Ramamurthi, Kumaran S

    2014-08-01

    Sporulation in the bacterium Bacillus subtilis is a developmental program in which a progenitor cell differentiates into two different cell types, the smaller of which eventually becomes a dormant cell called a spore. The process begins with an asymmetric cell division event, followed by the activation of a transcription factor, σF, specifically in the smaller cell. Here, we show that the structural protein DivIVA localizes to the polar septum during sporulation and is required for asymmetric division and the compartment-specific activation of σF. Both events are known to require a protein called SpoIIE, which also localizes to the polar septum. We show that DivIVA copurifies with SpoIIE and that DivIVA may anchor SpoIIE briefly to the assembling polar septum before SpoIIE is subsequently released into the forespore membrane and recaptured at the polar septum. Finally, using super-resolution microscopy, we demonstrate that DivIVA and SpoIIE ultimately display a biased localization on the side of the polar septum that faces the smaller compartment in which σF is activated.

  12. Space shuttle EVA/IVA support equipment requirements study. Volume 1: Final summary report

    NASA Technical Reports Server (NTRS)

    1973-01-01

    A study was conducted to determine the support equipment requirements for space shuttle intravehicular and extravehicular activities. The subjects investigated are; (1) EVA/IVA task identification and analysis,. (2) primary life support system, (3) emergency life support system, (4) pressure suit assembly, (5) restraints, (6) work site provision, (7) emergency internal vehicular emergencies, and (8) vehicular interfaces.

  13. GROWTH OF THE MARSH ELDER IVA FRUTESCENS IN RELATION TO DURATION OF TIDAL FLOODING

    EPA Science Inventory

    Iva frutescens is a common shrub at the upland fringe of salt marshes throughout the East and Gulf coasts of North America. Its position and relative size are governed largely by the degree of flooding by seawater. Cross sections of older stems (living and standing dead) from sa...

  14. GROWTH OF THE MARSH ELDER IVA FRUTESCENS IN RELATION TO DURATION OF TIDAL FLOODING

    EPA Science Inventory

    Iva frutescens is a common shrub at the upland fringe of salt marshes throughout the East and Gulf coasts of North America. Its position and relative size are governed largely by the degree of flooding by seawater. Cross sections of older stems (living and standing dead) from sa...

  15. Evaluation of 1980-81 Title IV-A Indian Education Program.

    ERIC Educational Resources Information Center

    Kimball, George H.

    1981-01-01

    The report evaluates the 1980-81 Title IV-A Indian Education Program consisting of three components designed to address special priority needs of Indian students in the Oklahoma City Public School System. Performance goals of the first component, supplementary academic assistance, were long-term tutoring of Indian students who scored below the…

  16. Title IV-A Indian Education Program Evaluation, 1984-85.

    ERIC Educational Resources Information Center

    Johns, Jennifer S.

    The Title IV-A Indian Education Program in Albuquerque, New Mexico, public schools met program objectives despite funding decreases, personnel cuts, and increased requests for remedial tutoring. Two tutors, a volunteer, and a counselor tutored 35 middle and high school students from the Navajo community of Canoncito to improve/maintain academic…

  17. Title IV-A Indian Education Program Evaluation, 1983-84.

    ERIC Educational Resources Information Center

    Johns, Jennifer S.

    The third year of Title IV-A Indian Education programs in Albuquerque, New Mexico, public schools saw fulfillment of some program objectives despite funding decreases, personnel cuts, and increased requests for remedial tutoring. Two tutors and a counselor tutored 15 middle school and 26 high school students from the Navajo community of Canoncito…

  18. Title IV-A Indian Education Program Evaluation, 1984-85.

    ERIC Educational Resources Information Center

    Johns, Jennifer S.

    The Title IV-A Indian Education Program in Albuquerque, New Mexico, public schools met program objectives despite funding decreases, personnel cuts, and increased requests for remedial tutoring. Two tutors, a volunteer, and a counselor tutored 35 middle and high school students from the Navajo community of Canoncito to improve/maintain academic…

  19. Title IV-A Indian Education Program Evaluation, 1983-84.

    ERIC Educational Resources Information Center

    Johns, Jennifer S.

    The third year of Title IV-A Indian Education programs in Albuquerque, New Mexico, public schools saw fulfillment of some program objectives despite funding decreases, personnel cuts, and increased requests for remedial tutoring. Two tutors and a counselor tutored 15 middle school and 26 high school students from the Navajo community of Canoncito…

  20. Predictors of periprocedural (type IVa) myocardial infarction, as assessed by frequency-domain optical coherence tomography.

    PubMed

    Porto, Italo; Di Vito, Luca; Burzotta, Francesco; Niccoli, Giampaolo; Trani, Carlo; Leone, Antonio M; Biasucci, Luigi M; Vergallo, Rocco; Limbruno, Ugo; Crea, Filippo

    2012-02-01

    Frequency-domain optical coherence tomography (FD-OCT) is easily able to define both pre- and post-stenting features of the atherosclerotic plaque that can potentially be related to periprocedural complications. We sought to examine which FD-OCT-defined characteristics, assessed both before and after stent deployment, predicted periprocedural (type IVa) myocardial infarction (MI). FD-OCT was performed before and after coronary stenting in 50 patients undergoing percutaneous coronary intervention (PCI) for either non-ST segment elevation MI (NSTEMI) or stable angina. All patients underwent single-vessel stenting, and only drug-eluting stents were implanted. Troponin T was analyzed on admission, before PCI, and at 12 and 24 hours after PCI, and type IVa MI was defined in stable angina as a rise of at least 3× upper reference limit and in NSTEMI as a pre-PCI troponin T fall, followed by post-PCI troponin T rise >20%. Type IVa MI was diagnosed in 21 patients, while the remaining 29 represented the control group. FD-OCT analysis showed that thin-cap fibroatheroma (76.2% versus 41.4%; P=0.017) prior to PCI, intrastent thrombus (61.9% versus 20.7%; P=0.04), and intrastent dissection (61.9% versus 31%; P=0.03) after PCI were significantly more frequent in type IVa MI than in the control group. Multivariate logistic regression analysis confirmed thin-cap fibroatheroma (OR 29.7, 95% CI 1.4 to 32.1), intrastent thrombus (OR 5.5, CI 1.2 to 24.9) and intrastent dissection (OR 5.3, CI 1.2 to 24.3) as independent predictors of type IVa MI. In conclusion, presence of thin-cap fibroatheroma at pre-PCI FD-OCT and of intrastent thrombus and intrastent dissection at post-PCI FD-OCT predict type IVa MI in a contemporary sample of patients treated with second-generation drug-eluting stents. Interestingly, 2 of the 3 predictors of type IVa MI were not apparent at pre-PCI FD-OCT.

  1. IRMA as a Potential Phase Correction Instrument: Results from the SMA Test Campaign

    NASA Astrophysics Data System (ADS)

    Naylor, David A.; Phillips, Robin R.; di Francesco, James; Bourke, Tyler L.; Querel, Richard R.; Jones, Scott C.

    2008-12-01

    The Infrared Radiometer for Millimetre Astronomy (IRMA) is a real-time water vapour monitor, whose sensitivity and temporal response make it a candidate instrument for the correction of phase distortion caused by atmospheric water vapour in millimetre wavelength interferometers. We present results from a test campaign in which two IRMA devices were mounted on two antennae of the Smithsonian Submillimeter Array (SMA) located atop Mauna Kea, Hawaii. The IRMA measurements are compared to each other, and to phase information derived from astronomical interferometric data to assess their utility as a potential tool in phase correction.

  2. Results of phase 2 of the APRICOT program. Final report. [LMFBR

    SciTech Connect

    Not Available

    1981-05-01

    APRICOT (Analysis of Primary Containment Transients) is a cooperative activity for comparison and benchmarking of computational methods used to analyze LMFBR (Liquid Metal Fast Breeder Reactor) structural response to pressure loads from HCDA's (Hypothetical Core Disruptive Accidents). Independent experts review the calculations for the purpose of comparing computational results and methods of solution. Phase 2 involved a series of more complex calculations based on the simulation of scaled-down containment experiments. These calculations, as those of Phase 1, were performed by participants from Europe, Japan and the United States. The calculations were all in reasonable agreement with experimental determinations of hydrodynamic loads; however, the calculated plastic strains differed significantly from the experimental results. The unresolved issues from the Phase 2 calculations are currently being studied with the calculations for Phase 3.

  3. [Morquio disease (Mucopolysaccharidosis type IV-A): clinical aspects, diagnosis and new treatment with enzyme replacement therapy].

    PubMed

    Politei, Juan; Schenone, Andrea B; Guelbert, Norberto; Fainboim, Alejandro; Szlago, Marina

    2015-08-01

    Mucopolysaccharidosis type IV-A (Morquio A disease) is an autosomal recessive lysosomal storage disease caused by mutations in the gene encoding the N-acetylgalactosamine-6-sulfate sulfatase, that results in impaired catabolism of two glycosaminoglycans, chondroitin-6-sulfate and keratan sulfate. Clinical presentations reflect a spectrum of progression from a severe phenotype to an attenuated expression. Accumulation of substrate manifests predominantly as short stature and skeletal dysplasia, including atlantoaxial instability and cervical cord compression. Other abnormalities in the visual, auditory, cardiovascular and respiratory systems can also affect individuals with Morquio disease. Elosulfase alfa showed in clinical trials in children and adults a significant and sustained improvement in endurance and urinary levels of keratan sulfate. Data from the ongoing observational, multinational Morquio A Registry Study will provide valuable information on the long-term efficacy and safety of elosulfase alfa in patients, as well as on the natural history of this very rare disease.

  4. Phase III Simplified Integrated Test (SIT) results - Space Station ECLSS testing

    NASA Technical Reports Server (NTRS)

    Roberts, Barry C.; Carrasquillo, Robyn L.; Dubiel, Melissa Y.; Ogle, Kathryn Y.; Perry, Jay L.; Whitley, Ken M.

    1990-01-01

    During 1989, phase III testing of Space Station Freedom Environmental Control and Life Support Systems (ECLSS) began at Marshall Space Flight Center (MSFC) with the Simplified Integrated Test. This test, conducted at the MSFC Core Module Integration Facility (CMIF), was the first time the four baseline air revitalization subsystems were integrated together. This paper details the results and lessons learned from the phase III SIT. Future plans for testing at the MSFC CMIF are also discussed.

  5. First Results on a Transatlantic Time and Frequency Transfer by GPS Carrier Phase

    DTIC Science & Technology

    1998-12-01

    FIRST RESULTS ON A TRANSATLANTIC TIME AND FREQUENCY TRANSFER BY GPS CARRIER PHASE G . Dudle, F. Overney, 1;. Prost Swiss Federal Office of...P. Hetzel P hysikalisch Techllische Bundesantalt Braunschweig, Germany E. Powers U.S. Naval Observatory, Washington, DC, USA A hstract Time and...frequency transfer hy GPS carrier phase, also referred to as Geodetic Time Transfer (GeTT), has been studied intensively in the frame of a

  6. Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: early treatment rescues bone lesions?

    PubMed

    Tomatsu, Shunji; Montaño, Adriana M; Oikawa, Hirotaka; Dung, Vu Chi; Hashimoto, Amiko; Oguma, Toshihiro; Gutiérrez, Monica L; Takahashi, Tatsuo; Shimada, Tsutomu; Orii, Tadao; Sly, William S

    2015-02-01

    We treated mucopolysaccharidosis IVA (MPS IVA) mice to assess the effects of long-term enzyme replacement therapy (ERT) initiated at birth, since adult mice treated by ERT showed little improvement in bone pathology [1]. To conduct ERT in newborn mice, we used recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in a CHO cell line. First, to observe the tissue distribution pattern, a dose of 250units/g body weight was administered intravenously in MPS IVA mice at day 2 or 3. The infused enzyme was primarily recovered in the liver and spleen, with detectable activity in the bone and brain. Second, newborn ERT was conducted after a tissue distribution study. The first injection of newborn ERT was performed intravenously, the second to fourth weekly injections were intraperitoneal, and the remaining injections from 5th to 14th weeks were intravenous into the tail vein. MPS IVA mice treated with GALNS showed clearance of lysosomal storage in the liver and spleen, and sinus lining cells in bone marrow. The column structure of the growth plate was organized better than that in adult mice treated with ERT; however, hyaline and fibrous cartilage cells in the femur, spine, ligaments, discs, synovium, and periosteum still had storage materials to some extent. Heart valves were refractory to the treatment. Levels of serum keratan sulfate were kept normal in newborn ERT mice. In conclusion, the enzyme, which enters the cartilage before the cartilage cell layer becomes mature, prevents disorganization of column structure. Early treatment from birth leads to partial remission of bone pathology in MPS IVA mice. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: early treatment rescues bone lesions?

    PubMed Central

    Tomatsu, Shunji; Montaño, Adriana M.; Oikawa, Hirotaka; Dung, Vu Chi; Hashimoto, Amiko; Oguma, Toshihiro; Takahashi, Tatsuo; Shimada, Tsutomu; Orii, Tadao; Sly, William S.

    2014-01-01

    We treated mucopolysaccharidosis IVA (MPS IVA) mice to assess the effects of long-term enzyme replacement therapy (ERT) initiated at birth, since adult mice treated by ERT showed little improvement in bone pathology (1). To conduct ERT in newborn mice, we used recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in a CHO cell line. First, to observe the tissue distribution pattern, a dose of 250 units/g body weight was administered intravenously in MPS IVA mice at day 2 or 3. The infused enzyme was primarily recovered in liver and spleen, with detectable activity in bone and brain. Second, newborn ERT was conducted after tissue distribution study. The first injection of newborn ERT was performed intravenously, the second to fourth weekly injections were intraperitoneal, and the remaining injections from 5th to 14th week were intravenous into the tail vein. MPS IVA mice treated with GALNS showed clearance of lysosomal storage in liver, spleen, and sinus lining cells in bone marrow. The column structure of the growth plate was organized better than adult mice treated with ERT; however, hyaline and fibrous cartilage cells in femur, spine, ligaments, discs, synovium, and periosteum still had storage materials to some extent. Heart valves were refractory to the treatment. Levels of serum keratan sulfate were kept normal in newborn ERT mice. In conclusion, the enzyme, which enters the cartilage before the cartilage cell layer becomes mature, prevents disorganization of column structure. Early treatment from birth leads to partial remission of bone pathology in MPS IVA mouse. PMID:24953405

  8. Concurrent chemoradiotherapy with nedaplatin in patients with stage IIA to IVA cervical carcinoma.

    PubMed

    Fujioka, Toru; Yasuoka, Toshiaki; Koizumi, Masae; Tanaka, Hiroki; Hashimoto, Hisashi; Nabeta, Motoo; Koizumi, Koji; Matsubara, Yuko; Hamada, Katsuyuki; Matsubara, Keiichi; Katayama, Tomihiro; Nawa, Akihiro

    2013-01-01

    The present study aimed to evaluate the efficacy and toxicities of nadaplatin-based concurrent chemoradiotherapy (CCRT) in patients with stage IIA to IVA cervical carcinoma. Patients with an International Federation of Gynecology and Obstetrics (FIGO) stage IIA to IVA cervical carcinoma were treated with nadaplatin-based CCRT, using high-dose rate intracavitary brachytherapy (HDR-ICBT) or radiotherapy (RT) alone, in patients with FIGO stage IIA to IVA cervical carcinoma. CCRT with nedaplatin (80 mg/m(2)) was administered on Days 1 and 29. The records of 17 women treated either with nadaplatin-based CCRT using HSR-ICBT (n=8) or RT alone (n=9), for stage IIA to IVA cervical carcinoma were retrospectively reviewed. The activity and toxicity were compared in the two treatment groups. Progression-free survival (PFS) and overall survival (OS) were the main endpoints. The 5-year overall survival rates in the CCRT and RT groups were 68.6 and 77.8%, respectively. The median OS of the CCRT and RT groups was 38.5 and 27.3 months, respectively. There was no significant difference in either PFS (P=0.618) or OS (P= 0.231). The most common grade 3-4 or higher toxicities in the CCRT groups were leuko-/neutropenia (37.5%). The frequency of acute grade 3-4 toxicity was higher in the CCRT compared to the RT group. However, no statistically significant difference was observed. Nedaplatin-based CCRT was safely performed. Although the prognosis of patients with FIGO stage IIA to IVA cervical carcinoma was not significantly improved, fewer distant relapses were observed in this treatment. Consequently, nedaplatin-based CCRT may be considered as a potential alternative to cisplatin-based CCRT in this patient population.

  9. Effective core potential modeling of Group IVA-Group IVB chemical vapor deposition

    SciTech Connect

    Cundari, T.R.; Li, Yueping

    1995-08-15

    An effective core potential study of a model chemical vapor deposition (CVD) reaction is reported. Compounds studied are those in which a Group IVA (E=C, Si, Ge, SN) main group element is directly bonded to a Group IVB (M=Ti, Zr, Hf) transition metal. Model reactants (H{sub 3}M-EH{sub 3}) possess Group IVA-Group IVB single bonds while products (H{sub 2}M = EH{sub 2}, formed by H{sub 2} elimination from reactants) have Group IVA-Group IVB multiple bonds. The main findings of this research are as follows: First, a single-determinant (RHF) description is appropriate for singly bonded Group IVA-Group IVB complexes. Agreement between experimental and calculated M-E single-bond lengths is very good at all levels studied. Second, electron correlation is of much greater importance for describing the ME {pi} bond than the ME {sigma} bond. Third, analysis of calculated double-to-single bond ratios (R{sub double}/R{sub single}) suggest that {pi}-bonding remains nearly constant over the entire series of compounds studied and is weaker than in the main group-main group analogs, suggesting a reason for the lack of reported examples with a Group IVA-Group IVB double bound. Fourth, barriers to elimination of H{sub 2} from H{sub 3}M-EH{sub 3} show two significant trends. We propose that the trends as a function of transition metal (Ti < Zr < Hf) and main group element (C > Si > Ge > Sn) are due to trends in M-H and E-H bond energies. 37 refs., 2 figs., 7 tabs.

  10. Recent findings on biosolids cake odor reduction--results of WERF phase 3 biosolids odor research.

    PubMed

    Erdal, Zeynep K; Forbes, Robert H; Witherspoon, Jay; Adams, Greg; Hargreaves, Ron; Morton, Rob; Novak, John; Higgins, Matthew

    2008-11-01

    The Water Environment Research Foundation (WERF) has sponsored three phases of a long-term project entitled "Identifying and Controlling Odors in the Municipal Wastewater Environment." The current (third) phase focuses on reduction of odors from dewatered biosolids cakes, and is entitled "Biosolids Processing Modifications for Cake Odor Reduction." This phase encompasses nine research agenda items developed from the results of the prior phase of research (Phase 2), which was completed in December 2003 as WERF Report No. 00-HHE-5T and was entitled "Impacts of In-Plant Parameters on Biosolids Odor Quality." The current phase (Phase 3) was a 2.5-year project, the first half of which was dedicated to testing several of the more promising hypotheses from Phase 2 in the laboratory to help determine the cause-effect relationships of odor generation from biosolids, and to develop odor reduction techniques. It is important to note that this research project covers the reduction or prevention of odorous emissions from dewatered biosolids cake, not odor control by means of containment or adsorption or absorption of malodorous emissions. In the remainder of the Phase 3 project, promising laboratory findings are being applied to biosolids handling processes at one or more wastewater treatment plants (WWTPs), with the goal of achieving significant cake odor reduction in a realistic, full-scale setting. The Phase 3 laboratory results were used to identify the relative effectiveness of methods for reducing biosolids cake odors, using techniques and measurements of biosolids cake odor production potential that have been developed by the WERF Project Team. Plans to demonstrate the most promising research findings at full-scale biosolids digestion and dewatering facilities constitute the final, fourth phase of the project. Contacts have been made with wastewater treatment facilities that have an interest or need to reduce their biosolids cake odors. The main goal of the next phase of

  11. Experiment of Injecting Phase Cal Ahead of the Feed: First Results

    NASA Technical Reports Server (NTRS)

    Ivanov, Dmitrij; Maslenikov, Anatolij; Vytnov, Alexander

    2010-01-01

    For developing the Russian VLBI network of new generation, a few experiments of injecting the phase calibration signal ahead of the feed were carried out. In the experiments an external broadband phase calibration signal was emitted through a special feed to a receiver horn directly. Prototypes of the feed for a frequency range of 2-18 GHz were created. The first experiments on injection phase cal ahead of the feed were carried out at Svetloe Observatory of the QUASAR VLBI network. The phase cal signal was emitted by the broadband feed installed on the roof of a mirror cabin, reflected by the sub-reflector, and received by the horn of the receiving system. The results of these experiments are considered.

  12. A synopsis of test results and knowledge gained from the Phase-0 CSI evolutionary model

    NASA Technical Reports Server (NTRS)

    Belvin, W. Keith; Elliott, Kenny B.; Horta, Lucas G.

    1993-01-01

    The Phase-0 CSI Evolutionary Model (CEM) is a testbed for the study of space platform global line-of-sight (LOS) pointing. Now that the tests have been completed, a summary of hardware and closed-loop test experiences is necessary to insure a timely dissemination of the knowledge gained. The testbed is described and modeling experiences are presented followed by a summary of the research performed by various investigators. Some early lessons on implementing the closed-loop controllers are described with particular emphasis on real-time computing requirements. A summary of closed-loop studies and a synopsis of test results are presented. Plans for evolving the CEM from phase 0 to phases 1 and 2 are also described. Subsequently, a summary of knowledge gained from the design and testing of the Phase-0 CEM is made.

  13. First results of GERDA Phase II and consistency with background models

    NASA Astrophysics Data System (ADS)

    Agostini, M.; Allardt, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode1, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gooch, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Palioselitis, D.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Selivanenko, O.; Shevzik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.

    2017-01-01

    The GERDA (GERmanium Detector Array) is an experiment for the search of neutrinoless double beta decay (0νββ) in 76Ge, located at Laboratori Nazionali del Gran Sasso of INFN (Italy). GERDA operates bare high purity germanium detectors submersed in liquid Argon (LAr). Phase II of data-taking started in Dec 2015 and is currently ongoing. In Phase II 35 kg of germanium detectors enriched in 76Ge including thirty newly produced Broad Energy Germanium (BEGe) detectors is operating to reach an exposure of 100 kg·yr within about 3 years data taking. The design goal of Phase II is to reduce the background by one order of magnitude to get the sensitivity for T1/20ν = O≤ft( {{{10}26}} \\right){{ yr}}. To achieve the necessary background reduction, the setup was complemented with LAr veto. Analysis of the background spectrum of Phase II demonstrates consistency with the background models. Furthermore 226Ra and 232Th contamination levels consistent with screening results. In the first Phase II data release we found no hint for a 0νββ decay signal and place a limit of this process T1/20ν > 5.3 \\cdot {1025} yr (90% C.L., sensitivity 4.0·1025 yr). First results of GERDA Phase II will be presented.

  14. An Update on Phased Array Results Obtained on the GE Counter-Rotating Open Rotor Model

    NASA Technical Reports Server (NTRS)

    Podboy, Gary; Horvath, Csaba; Envia, Edmane

    2013-01-01

    Beamform maps have been generated from 1) simulated data generated by the LINPROP code and 2) actual experimental phased array data obtained on the GE Counter-rotating open rotor model. The beamform maps show that many of the tones in the experimental data come from their corresponding Mach radius. If the phased array points to the Mach radius associated with a tone then it is likely that the tone is a result of the loading and thickness noise on the blades. In this case, the phased array correctly points to where the noise is coming from and indicates the axial location of the loudest source in the image but not necessarily the correct vertical location. If the phased array does not point to the Mach radius associated with a tone then some mechanism other than loading and thickness noise may control the amplitude of the tone. In this case, the phased array may or may not point to the actual source. If the source is not rotating it is likely that the phased array points to the source. If the source is rotating it is likely that the phased array indicates the axial location of the loudest source but not necessarily the correct vertical location. These results indicate that you have to be careful in how you interpret phased array data obtained on an open rotor since they may show the tones coming from a location other than the source location. With a subsonic tip speed open rotor the tones can come form locations outboard of the blade tips. This has implications regarding noise shielding.

  15. Who benefits from chemoradiation in stage III-IVA endometrial cancer? An analysis of the National Cancer Data Base.

    PubMed

    Lester-Coll, Nataniel H; Park, Henry S; Rutter, Charles E; Corso, Christopher D; Young, Melissa R; Ratner, Elena S; Litkouhi, Babak; Decker, Roy H; Yu, James B; Damast, Shari

    2016-07-01

    Adjuvant therapy for advanced endometrial cancer (AEC) is not standardized. We investigated whether regional radiotherapy with chemotherapy (CRT) compared to chemotherapy alone (CT) was associated with improved overall survival (OS) in an AEC cohort and among subgroups by stage and histologic grade. Women who received CT or CRT after hysterectomy and bilateral salpingo-oophorectomy for FIGO stage III-IVA AEC diagnosed in 2004-2012 were identified in the National Cancer Data Base. Multilevel modeling was used to identify covariates associated with treatment selection. OS was compared using Kaplan-Meier estimates, the log-rank test, Cox proportional hazards regression, and propensity score matching. We identified 9837 patients, of whom 6358 (65%) received CT and 3479 (35%) received CRT. Median follow-up was 59.6months. OS was higher in patients receiving CRT compared to CT (70% v 55% at 5years, log-rank P<0.001). Controlling for stage, histologic grade, tumor size, age, comorbidity and race, CRT remained independently associated with improved OS (HR 0.63, 95% CI 0.57-0.70, P<0.001). When stratified by stage and histologic grade, there was a significant OS benefit for stage IIIA, IIIB, IIIC, grade 2, and grade 3 (all P<0.001), a trend for stage IVA (P=0.06), but no benefit for grade 1 (P=0.91). On multivariable subgroup analyses, these findings persisted, including lack of benefit in grade 1 patients (HR 0.72, P=0.14). These results were further confirmed after propensity score matching. Adjuvant CRT for AEC was associated with improved OS, except for patients with well-differentiated disease, who fared equally well with CT alone. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Mechanical Abrasion as a Low Cost Technique for Contamination-Free Sample Acquisition from a Category IVA Clean Platform

    NASA Technical Reports Server (NTRS)

    Dolgin, B.; Yarbrough, C.; Carson, J.; Troy, R.

    2000-01-01

    The proposed Mars Sample Transfer Chain Architecture provides Planetary Protection Officers with clean samples that are required for the eventual release from confinement of the returned Martian samples. At the same time, absolute cleanliness and sterility requirement is not placed of any part of the Lander (including the deep drill), Mars Assent Vehicle (MAV), any part of the Orbiting Sample container (OS), Rover mobility platform, any part of the Minicorer, Robotic arm (including instrument sensors), and most of the caching equipment on the Rover. The removal of the strict requirements in excess of the Category IVa cleanliness (Pathfinder clean) is expected to lead to significant cost savings. The proposed architecture assumes that crosscontamination renders all surfaces in the vicinity of the rover(s) and the lander(s) contaminated. Thus, no accessible surface of Martian rocks and soil is Earth contamination free. As a result of the latter, only subsurface samples (either rock or soil) can be and will be collected for eventual return to Earth. Uncontaminated samples can be collected from a Category IVa clean platform. Both subsurface soil and rock samples can be maintained clean if they are collected by devices that are self-contained and clean and sterile inside only. The top layer of the sample is removed in a manner that does not contaminate the collection tools. Biobarrier (e.g., aluminum foil) covering the moving parts of these devices may be used as the only self removing bio-blanket that is required. The samples never leave the collection tools. The lids are placed on these tools inside the collection device. These single use tools with the lid and the sample inside are brought to Earth in the OS. The lids have to be designed impenetrable to the Earth organisms. The latter is a well established art.

  17. Multi-modal data fusion using source separation: Two effective models based on ICA and IVA and their properties

    PubMed Central

    Adali, Tülay; Levin-Schwartz, Yuri; Calhoun, Vince D.

    2015-01-01

    Fusion of information from multiple sets of data in order to extract a set of features that are most useful and relevant for the given task is inherent to many problems we deal with today. Since, usually, very little is known about the actual interaction among the datasets, it is highly desirable to minimize the underlying assumptions. This has been the main reason for the growing importance of data-driven methods, and in particular of independent component analysis (ICA) as it provides useful decompositions with a simple generative model and using only the assumption of statistical independence. A recent extension of ICA, independent vector analysis (IVA) generalizes ICA to multiple datasets by exploiting the statistical dependence across the datasets, and hence, as we discuss in this paper, provides an attractive solution to fusion of data from multiple datasets along with ICA. In this paper, we focus on two multivariate solutions for multi-modal data fusion that let multiple modalities fully interact for the estimation of underlying features that jointly report on all modalities. One solution is the Joint ICA model that has found wide application in medical imaging, and the second one is the the Transposed IVA model introduced here as a generalization of an approach based on multi-set canonical correlation analysis. In the discussion, we emphasize the role of diversity in the decompositions achieved by these two models, present their properties and implementation details to enable the user make informed decisions on the selection of a model along with its associated parameters. Discussions are supported by simulation results to help highlight the main issues in the implementation of these methods. PMID:26525830

  18. Chemoradiotherapy followed by consolidation chemotherapy involving paclitaxel and carboplatin and in FIGO stage IIIB/IVA cervical cancer patients

    PubMed Central

    2017-01-01

    Objective To evaluate the efficacy and toxicity of paclitaxel plus carboplatin (TC)-based concurrent chemoradiotherapy (CCRT) followed by consolidation chemotherapy in the International Federation of Gynecology and Obstetrics (FIGO) stage IIIB/IVA cervical cancer patients. Methods We reviewed the medical records of FIGO stage IIIB/IVA cervical cancer patients (n=30) who had been intended to be treated with TC-based CCRT followed by consolidation chemotherapy (TC-CCRT-group) from April 2012–May 2016. Patients who had been treated with CCRT involving a single platinum agent (CCRT-group; n=52) or definitive radiotherapy alone (RT-group; n=74) from January 1997–September 2012 were also identified and used as historical controls. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test. Results Of the 30 patients included in the TC-CCRT-group, 22 patients (73.3%) completed the planned TC-based CCRT. The most frequently observed acute grade 3/4 hematological toxicities were leukopenia and neutropenia, and diarrhea was the most common acute grade 3/4 non-hematological toxicity. After a median follow-up of 35 months, 9 patients (30.0%) had developed recurrent disease. The patients’ estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 67.9% and 90.8%, respectively. In comparisons with historical control groups, the survival outcomes of TC-CCRT-group was significantly superior to CCRT-group in terms of OS (p=0.011) and significantly superior to RT-group in terms of both PFS (p=0.009) and OS (p<0.001). Conclusion TC-based CCRT followed by consolidation chemotherapy is safe and effective. A randomized controlled study needs to be conducted to further evaluate the efficacy of this multimodal approach in this patient population. PMID:27958682

  19. Mechanical Abrasion as a Low Cost Technique for Contamination-Free Sample Acquisition from a Category IVA Clean Platform

    NASA Technical Reports Server (NTRS)

    Dolgin, B.; Yarbrough, C.; Carson, J.; Troy, R.

    2000-01-01

    The proposed Mars Sample Transfer Chain Architecture provides Planetary Protection Officers with clean samples that are required for the eventual release from confinement of the returned Martian samples. At the same time, absolute cleanliness and sterility requirement is not placed of any part of the Lander (including the deep drill), Mars Assent Vehicle (MAV), any part of the Orbiting Sample container (OS), Rover mobility platform, any part of the Minicorer, Robotic arm (including instrument sensors), and most of the caching equipment on the Rover. The removal of the strict requirements in excess of the Category IVa cleanliness (Pathfinder clean) is expected to lead to significant cost savings. The proposed architecture assumes that crosscontamination renders all surfaces in the vicinity of the rover(s) and the lander(s) contaminated. Thus, no accessible surface of Martian rocks and soil is Earth contamination free. As a result of the latter, only subsurface samples (either rock or soil) can be and will be collected for eventual return to Earth. Uncontaminated samples can be collected from a Category IVa clean platform. Both subsurface soil and rock samples can be maintained clean if they are collected by devices that are self-contained and clean and sterile inside only. The top layer of the sample is removed in a manner that does not contaminate the collection tools. Biobarrier (e.g., aluminum foil) covering the moving parts of these devices may be used as the only self removing bio-blanket that is required. The samples never leave the collection tools. The lids are placed on these tools inside the collection device. These single use tools with the lid and the sample inside are brought to Earth in the OS. The lids have to be designed impenetrable to the Earth organisms. The latter is a well established art.

  20. Multi-modal data fusion using source separation: Two effective models based on ICA and IVA and their properties.

    PubMed

    Adali, Tülay; Levin-Schwartz, Yuri; Calhoun, Vince D

    2015-09-01

    Fusion of information from multiple sets of data in order to extract a set of features that are most useful and relevant for the given task is inherent to many problems we deal with today. Since, usually, very little is known about the actual interaction among the datasets, it is highly desirable to minimize the underlying assumptions. This has been the main reason for the growing importance of data-driven methods, and in particular of independent component analysis (ICA) as it provides useful decompositions with a simple generative model and using only the assumption of statistical independence. A recent extension of ICA, independent vector analysis (IVA) generalizes ICA to multiple datasets by exploiting the statistical dependence across the datasets, and hence, as we discuss in this paper, provides an attractive solution to fusion of data from multiple datasets along with ICA. In this paper, we focus on two multivariate solutions for multi-modal data fusion that let multiple modalities fully interact for the estimation of underlying features that jointly report on all modalities. One solution is the Joint ICA model that has found wide application in medical imaging, and the second one is the the Transposed IVA model introduced here as a generalization of an approach based on multi-set canonical correlation analysis. In the discussion, we emphasize the role of diversity in the decompositions achieved by these two models, present their properties and implementation details to enable the user make informed decisions on the selection of a model along with its associated parameters. Discussions are supported by simulation results to help highlight the main issues in the implementation of these methods.

  1. Experimental results of the performance of the new phase and frequency controller

    NASA Astrophysics Data System (ADS)

    Mannermaa, Jari; Kalliomaeki, Kalevi

    1992-06-01

    The application of the Maximum Entropy Method (MEM) to control phase locked crystals of Loran C receivers is reported. Performance optimization of the MEM controller achieved the result of 9 ns and 7 x 10(exp -12) for phase and frequency residuals, respectively. These values are comparable with 100 ns and 9 x 10(exp -12) of the older conventional PI controller, respectively. The performance of the MEM controlled Loran C receiver is at least 50 percent better when compared with the identical receiver equipped with the PI controller. The results verify the presumed superiority of the MEM controller over the conventional PI.

  2. MSFC Sortie Laboratory Environmental Control System (ECS) phase B design study results

    NASA Technical Reports Server (NTRS)

    Ignatonis, A. J.; Mitchell, K. L.

    1974-01-01

    Phase B effort of the Sortie Lab program has concluded. Results of that effort are presented which pertain to the definitions of the environmental control system (ECS). Numerous design studies were performed in Phase B to investigate system feasibility, complexity, weight, and cost. The results and methods employed for these design studies are included. An autonomous Sortie Lab ECS was developed which utilizes a deployed space radiator. Total system weight was projected to be 1814.4 kg including the radiator and fluids. ECS power requirements were estimated at 950 watts.

  3. Crystal structures of the substrate free-enzyme, and reaction intermediate of the HAD superfamily member, haloacid dehalogenase DehIVa from Burkholderia cepacia MBA4.

    PubMed

    Schmidberger, Jason W; Wilce, Jackie A; Tsang, Jimmy S H; Wilce, Matthew C J

    2007-05-04

    DehIVa is a haloacid dehalogenase (EC 3.8.1.2) from the soil and water borne bacterium Burkholderia cepacia MBA4, which belongs to the functionally variable haloacid dehalogenase (HAD) superfamily of enzymes. The haloacid dehalogenases catalyse the removal of halides from haloacids resulting in a hydroxlated product. These enzymes are of interest for their potential to degrade recalcitrant halogenated environmental pollutants and their use in the synthesis of industrial chemicals. The haloacid dehalogenases utilise a nucleophilic attack on the substrate by an aspartic acid residue to form an enzyme-substrate ester bond and concomitantly cleaving of the carbon-halide bond and release of a hydroxylated product following ester hydrolysis. We present the crystal structures of both the substrate-free DehIVa refined to 1.93 A resolution and DehIVa covalently bound to l-2-monochloropropanoate trapped as a reaction intermediate, refined to 2.7 A resolution. Electron density consistent with a previously unidentified yet anticipated water molecule in the active site poised to donate its hydroxyl group to the product and its proton to the catalytic Asp11 is evident. It has been unclear how substrate enters the active site of this and related enzymes. The results of normal mode analysis (NMA) are presented and suggest a means whereby the predicted global dynamics of the enzyme allow for entry of the substrate into the active site. In the context of these results, the possible role of Arg42 and Asn178 in a "lock down" mechanism affecting active site access is discussed. In silico substrate docking of enantiomeric substrates has been examined in order to evaluate the enzymes enantioselectivity.

  4. Effect of Carbon Ion Radiotherapy for Sacral Chordoma: Results of Phase I-II and Phase II Clinical Trials

    SciTech Connect

    Imai, Reiko; Kamada, Tadashi; Tsuji, Hiroshi; Sugawara, Shinji; Serizawa, Itsuko; Tsujii, Hirohiko; Tatezaki, Shin-ichiro

    2010-08-01

    Purpose: To summarize the results of treatment for sacral chordoma in Phase I-II and Phase II carbon ion radiotherapy trials for bone and soft-tissue sarcomas. Patients and Methods: We performed a retrospective analysis of 38 patients with medically unresectable sacral chordomas treated with the Heavy Ion Medical Accelerator in Chiba, Japan between 1996 and 2003. Of the 38 patients, 30 had not received previous treatment and 8 had locally recurrent tumor after previous resection. The applied carbon ion dose was 52.8-73.6 Gray equivalents (median, 70.4) in a total of 16 fixed fractions within 4 weeks. Results: The median patient age was 66 years. The cranial tumor extension was S2 or greater in 31 patients. The median clinical target volume was 523 cm{sup 3}. The median follow-up period was 80 months. The 5-year overall survival rate was 86%, and the 5-year local control rate was 89%. After treatment, 27 of 30 patients with primary tumor remained ambulatory with or without supportive devices. Two patients experienced severe skin or soft-tissue complications requiring skin grafts. Conclusion: Carbon ion radiotherapy appears effective and safe in the treatment of patients with sacral chordoma and offers a promising alternative to surgery.

  5. Radiation Therapy and Cisplatin With or Without Triapine in Treating Patients With Newly Diagnosed Stage IB2, II, or IIIB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer

    ClinicalTrials.gov

    2017-10-09

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB2 Cervical Cancer; Stage II Cervical Cancer; Stage II Vaginal Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Vaginal Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Vaginal Cancer; Vaginal Adenocarcinoma; Vaginal Adenosquamous Carcinoma; Vaginal Squamous Cell Carcinoma, Not Otherwise Specified

  6. The Type IVa Pilus Machinery Is Recruited to Sites of Future Cell Division

    PubMed Central

    Carter, Tyson; Buensuceso, Ryan N. C.; Tammam, Stephanie; Lamers, Ryan P.; Harvey, Hanjeong

    2017-01-01

    ABSTRACT Type IVa pili (T4aP) are ubiquitous microbial appendages used for adherence, twitching motility, DNA uptake, and electron transfer. Many of these functions depend on dynamic assembly and disassembly of the pilus by a megadalton-sized, cell envelope-spanning protein complex located at the poles of rod-shaped bacteria. How the T4aP assembly complex becomes integrated into the cell envelope in the absence of dedicated peptidoglycan (PG) hydrolases is unknown. After ruling out the potential involvement of housekeeping PG hydrolases in the installation of the T4aP machinery in Pseudomonas aeruginosa, we discovered that key components of inner (PilMNOP) and outer (PilQ) membrane subcomplexes are recruited to future sites of cell division. Midcell recruitment of a fluorescently tagged alignment subcomplex component, mCherry-PilO, depended on PilQ secretin monomers—specifically, their N-terminal PG-binding AMIN domains. PilP, which connects PilO to PilQ, was required for recruitment, while PilM, which is structurally similar to divisome component FtsA, was not. Recruitment preceded secretin oligomerization in the outer membrane, as loss of the PilQ pilotin PilF had no effect on localization. These results were confirmed in cells chemically blocked for cell division prior to outer membrane invagination. The hub protein FimV and a component of the polar organelle coordinator complex—PocA—were independently required for midcell recruitment of PilO and PilQ. Together, these data suggest an integrated, energy-efficient strategy for the targeting and preinstallation—rather than retrofitting—of the T4aP system into nascent poles, without the need for dedicated PG-remodeling enzymes. PMID:28143978

  7. Corrections of diverse forms of lower limb deformities in patients with mucopolysaccharidosis type IVA (Morquio syndrome)

    PubMed Central

    Al Kaissi, Ali; Kenis, Vladimir; Melchenko, Eugeniy; Ghachem, Maher Ben; Csepan, Robert; Grill, Franz; Ganger, Rudolf

    2016-01-01

    Background: Thoracolumbar kyphosis has been considered as the first presenting deformity and is often a key diagnostic clue noted in children with mucopolysaccharidosis (MPS) type IV (Morquio's syndrome). However, we observed that the progressive irregularities of the epiphyses of the long bones were the most prominent skeletal pathology, causing effectively the development of diverse forms of lower limbs deformities with extreme variation in age of onset. Materials and Methods: Ten patients (seven children and three adults) with an average age of 15 years have been enrolled in this study. Age of diagnosis of MPS IVA has a variable age of onset and a MISLEADING rate of severity. Hip dislocations, genu valgum, protrusio acetabuli and osteoarthritis were the most common lower limbs deformities in these patients. Clinical and radiographic phenotypes were the baseline tools of documentation. Urinary screening and genotypic characterizations have been applied accordingly. Results: Combined pelvic and femoral procedures for hip dislocation, epiphysiodeses and supracondylar osteotomy for genu valgum and hip arthroplasty for protrusio acetabuli have been performed. All patients manifested insufficient activity of N-acetylgalactosamine-6-sulphate sulphatase, an enzyme that degrades keratin sulphate and chondroitin-6 sulphate. Conclusion: The extensive clinical heterogeneity contributed significantly in the delay in establishing the diagnosis particularly in adult patients with MPS IV. The epiphyseal irregularities of the long bones and the progressive flattening pathology of MPS IV A were the reason to falsely diagnose some patients as spondyloepiphyseal dysplasia congenital and/or tarda. Proximal femoral osteotomy, realignment osteotomy and total hip arthroplasty have been performed for coxa vara, genu valgum and protrusio acetabuli, respectively, in children and adult group of patients. The importance of early diagnosis on MPS IV A is to receive enzyme replacement therapy

  8. Acute and chronic toxicological studies of Ajuga iva in experimental animals.

    PubMed

    El Hilaly, Jaouad; Israili, Zafar H; Lyoussi, Badiâa

    2004-03-01

    Ajuga iva (L.) Schreber (AI), is widely used in the Moroccan pharmacopoeia as a panacea (cure-all), and specifically for gastrointestinal disorders and diabetes, and as an anthelmintic. No toxicological investigations have been carried out on this plant. We have previously observed that single oral doses (2-14 g/kg) of a lyophilised aqueous extract of AI (AI-extract) in mice or daily oral administration of 10 mg/kg of AI-extract in rats for 2 weeks did not result in any adverse effects. We have now evaluated AI-extract for its behavioural and pharmaco-toxicological effects after acute and chronic administration by the oral and intraperitoneal routes in rats and mice. No toxicity was observed in mice after single oral doses of as high as 14 g/kg of the AI-extract. However, single intraperitoneal injections of the AI-extract (1500-5500 mg/kg BW) produced a dose-dependent increase in adverse effects in the general behaviour and the mortality rate; the LD50 of acute intraperitoneal dose was 3.6 g/kg. In chronic toxicological studies in rats, the AI-extract (administered orally at daily doses of 100, 300 and 600 mg/kg for 3 months), did not cause any changes in haematological and biochemical parameters, with the exception of a transient rise in platelet counts and a short-term decrease in serum glucose levels. Histopathological examination of the brain, liver and the kidneys at the end of the study (3 months) showed normal architecture suggesting no morphological disturbances.

  9. The Type IVa Pilus Machinery Is Recruited to Sites of Future Cell Division.

    PubMed

    Carter, Tyson; Buensuceso, Ryan N C; Tammam, Stephanie; Lamers, Ryan P; Harvey, Hanjeong; Howell, P Lynne; Burrows, Lori L

    2017-01-31

    Type IVa pili (T4aP) are ubiquitous microbial appendages used for adherence, twitching motility, DNA uptake, and electron transfer. Many of these functions depend on dynamic assembly and disassembly of the pilus by a megadalton-sized, cell envelope-spanning protein complex located at the poles of rod-shaped bacteria. How the T4aP assembly complex becomes integrated into the cell envelope in the absence of dedicated peptidoglycan (PG) hydrolases is unknown. After ruling out the potential involvement of housekeeping PG hydrolases in the installation of the T4aP machinery in Pseudomonas aeruginosa, we discovered that key components of inner (PilMNOP) and outer (PilQ) membrane subcomplexes are recruited to future sites of cell division. Midcell recruitment of a fluorescently tagged alignment subcomplex component, mCherry-PilO, depended on PilQ secretin monomers-specifically, their N-terminal PG-binding AMIN domains. PilP, which connects PilO to PilQ, was required for recruitment, while PilM, which is structurally similar to divisome component FtsA, was not. Recruitment preceded secretin oligomerization in the outer membrane, as loss of the PilQ pilotin PilF had no effect on localization. These results were confirmed in cells chemically blocked for cell division prior to outer membrane invagination. The hub protein FimV and a component of the polar organelle coordinator complex-PocA-were independently required for midcell recruitment of PilO and PilQ. Together, these data suggest an integrated, energy-efficient strategy for the targeting and preinstallation-rather than retrofitting-of the T4aP system into nascent poles, without the need for dedicated PG-remodeling enzymes.

  10. A compilation of results pertaining to the behavior of phase locked loops

    NASA Technical Reports Server (NTRS)

    Gleicher, N.

    1971-01-01

    State-of-the art on phase locked loops PLL is reported by summarizing some specific results. Following a statement of the overall analysis and design objectives, results are presented in a format identifying working terminology, inherent assumptions, and references for each result. The use of PLL in tracking, synchronization, and demodulation is reemphasized, as well as the mathematical challenge involved in solving nonlinear stochastic differential equations.

  11. Subclassification of stage IV gastric cancer (IVa, IVb, and IVc) and prognostic significance of substages.

    PubMed

    Ma, Yan; Xue, Yingwei; Li, Yanfeng; Lan, Xiuwen; Zhang, Yongle; Zhang, Ming

    2010-03-01

    Although the prognosis of stage IV gastric cancer is poor, some patients with stage IV gastric cancer had a long-term survival after gastrectomy. The objective of this study was to subclassify stage IV gastric cancer according to survival differences, evaluate the prognosis by substage, and identify the factors associated with patient survival in each substage. The data from 1,176 patients who underwent gastric resection for stage IV gastric cancer between 1988 and 2007 at Tumor Hospital of Harbin Medical University were reviewed retrospectively. The patients were divided into three substages according to the survival differences: stage IVa (T1-2N3M0), stage IVb (T3N3M0 and T4N1-2M0), and stage IVc (T4N3M0 and TanyNanyM1). The clinicopathological characteristics as well as survival of the patients were evaluated retrospectively by substage. There were no significant differences in survival among T3N3M0, T4N1M0, and T4N2M0 groups (p = 0.884) and between T4N3M0 and TanyNanyM1 groups (p = 0.192). The 5-year survival rates in stage IVa (T1-2N3M0), stage IVb (T3N3M0 and T4N1-2M0), and stage IVc (T4N3M0 and TanyNanyM1) were 22.7%, 9.9%, and 2.2%, respectively (p < 0.001). Multivariate analysis showed the following independent prognostic factors for survival: subclassification, operation type, number of retrieved lymph nodes, curability, and chemotherapy for stage IV gastric cancer; curability, chemotherapy, and number of retrieved lymph nodes for stage IVa and IVb; chemotherapy and operation type for stage IVc. For 406 patients with curative resection in stage IVa and IVb, hematogenous recurrence (35.9%) was the dominant recurrence pattern in stage IVa, whereas the most common patterns of recurrence were peritoneal (40.8%) and locoregional recurrence (31.8%) in stage IVb. Subclassification of stage IV gastric cancer into IVa (T1-2N3M0), IVb (T3N3M0 and T4N1-2M0), and IVc (T4N3M0, TanyNanyM1) may be helpful to predict the outcome and determine the therapeutic strategies

  12. Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

    ClinicalTrials.gov

    2014-12-29

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  13. Cisplatin and Radiation Therapy Followed by Paclitaxel and Carboplatin in Treating Patients With Stage IB-IVA Cervical Cancer

    ClinicalTrials.gov

    2017-05-03

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  14. Development of a fluorometric microtiter plate based enzyme assay for MPS IVA (Morquio type A) using dried blood spots.

    PubMed

    Ullal, Anirudh J; Millington, David S; Bali, Deeksha S

    2014-01-01

    Mucopolysaccharidosis type IVA or Morquio type-A disease is a hereditary lysosomal storage disorder caused by deficient activity of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). The disease is caused by lysosomal accumulation of unprocessed glycosaminoglycans (GAGs) that manifests with severe to mild skeletal and cardiopulmonary abnormalities. We have developed a modified microtiter plate-based enzyme activity assay using dried blood spots and a fluorescent substrate for measuring specific GALNS activity to identify patients with MPS IVA.

  15. Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vulvar Cancer

    ClinicalTrials.gov

    2017-09-12

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Vulvar Cancer; Stage IB2 Cervical Cancer; Stage II Vulvar Cancer; Stage IIA1 Cervical Cancer; Stage IIA2 Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Cervical Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVA Cervical Cancer; Stage IVA Vulvar Cancer; Vulvar Adenocarcinoma; Vulvar Squamous Cell Carcinoma

  16. The NASA broad-specification fuels combustion technology program: An assessment of phase 1 test results

    NASA Technical Reports Server (NTRS)

    Fear, J. S.

    1983-01-01

    An assessment is made of the results of Phase 1 screening testing of current and advanced combustion system concepts using several broadened-properties fuels. The severity of each of several fuels-properties effects on combustor performance or liner life is discussed, as well as design techniques with the potential to offset these adverse effects. The selection of concepts to be pursued in Phase 2 refinement testing is described. This selection takes into account the relative costs and complexities of the concepts, the current outlook on pollutant emissions control, and practical operational problems.

  17. Tandem Mass Spectrometry Has a Larger Analytical Range than Fluorescence Assays of Lysosomal Enzymes: Application to Newborn Screening and Diagnosis of Mucopolysaccharidoses Types II, IVA, and VI

    PubMed Central

    Kumar, Arun Babu; Masi, Sophia; Ghomashchi, Farideh; Chennamaneni, Naveen Kumar; Ito, Makoto; Scott, C. Ronald; Turecek, Frantisek; Gelb, Michael H.; Spacil, Zdenek

    2016-01-01

    BACKGROUND There is interest in newborn screening and diagnosis of lysosomal storage diseases because of the development of treatment options that improve clinical outcome. Assays of lysosomal enzymes with high analytical range (ratio of assay response from the enzymatic reaction divided by the assay response due to nonenzymatic processes) are desirable because they are predicted to lead to a lower rate of false positives in population screening and to more accurate diagnoses. METHODS We designed new tandem mass spectrometry (MS/MS) assays that give the largest analytical ranges reported to date for the use of dried blood spots (DBS) for detection of mucopolysaccharidoses type II (MPS-II), MPS-IVA, and MPS-VI. For comparison, we carried out fluorometric assays of 6 lysosomal enzymes using 4-methylumbelliferyl (4MU)-substrate conjugates. RESULTS The MS/MS assays for MPS-II, -IVA, and -VI displayed analytical ranges that are 1–2 orders of magnitude higher than those for the corresponding fluorometric assays. The relatively small analytical ranges of the 4MU assays are due to the intrinsic fluorescence of the 4MU substrates, which cause high background in the assay response. CONCLUSIONS These highly reproducible MS/MS assays for MPS-II, -IVA, and -VI can support multiplex newborn screening of these lysosomal storage diseases. MS/MS assays of lysosomal enzymes outperform 4MU fluorometric assays in terms of analytical range. Ongoing pilot studies will allow us to gauge the impact of the increased analytical range on newborn screening performance. PMID:26369786

  18. Surrogate/spent fuel sabotage aerosol ratio testing:phase 1 summary and results.

    SciTech Connect

    Vigil, Manuel Gilbert; Sorenson, Ken Bryce; Lange, F. , Germany); Nolte, O. (Fraunhofer Institut fur Toxikologie und Experimentelle Medizin, Germany); Koch, W. (Fraunhofer Institut fur Toxikologie und Experimentelle Medizin, Germany); Dickey, Roy R.; Yoshimura, Richard Hiroyuki; Molecke, Martin Alan; Autrusson, Bruno (Institut de Radioprotection et de Surete Nucleaire , France); Young, F. I.; Pretzsch, Gunter Guido (Gesellschaft fur Anlagen- und reaktorsicherheit , Germany)

    2005-10-01

    This multinational test program is quantifying the aerosol particulates produced when a high energy density device (HEDD) impacts surrogate material and actual spent fuel test rodlets. The experimental work, performed in four consecutive test phases, has been in progress for several years. The overall program provides needed data that are relevant to some sabotage scenarios in relation to spent fuel transport and storage casks, and associated risk assessments. This program also provides significant political benefits in international cooperation for nuclear security related evaluations. The spent fuel sabotage--aerosol test program is coordinated with the international Working Group for Sabotage Concerns of Transport and Storage Casks (WGSTSC), and supported by both the U.S. Department of Energy and Nuclear Regulatory Commission. This report summarizes the preliminary, Phase 1 work performed in 2001 and 2002 at Sandia National Laboratories and the Fraunhofer Institute, Germany, and documents the experimental results obtained, observations, and preliminary interpretations. Phase 1 testing included: performance quantifications of the HEDD devices; characterization of the HEDD or conical shaped charge (CSC) jet properties with multiple tests; refinement of the aerosol particle collection apparatus being used; and, CSC jet-aerosol tests using leaded glass plates and glass pellets, serving as representative brittle materials. Phase 1 testing was quite important for the design and performance of the following Phase 2 test program and test apparatus.

  19. Impact of the volume of gaseous phase in closed reactors on ANC results and modelling

    NASA Astrophysics Data System (ADS)

    Drapeau, Clémentine; Delolme, Cécile; Lassabatere, Laurent; Blanc, Denise

    2016-04-01

    The understanding of the geochemical behavior of polluted solid materials is often challenging and requires huge expenses of time and money. Nevertheless, given the increasing amounts of polluted solid materials and related risks for the environment, it is more and more crucial to understand the leaching of majors and trace metals elements from these matrices. In the designs of methods to quantify pollutant solubilization, the combination of experimental procedures with modeling approaches has recently gained attention. Among usual methods, some rely on the association of ANC and geochemical modeling. ANC experiments - Acid Neutralization Capacity - consists in adding known quantities of acid or base to a mixture of water and contaminated solid materials at a given liquid / solid ratio in closed reactors. Reactors are agitated for 48h and then pH, conductivity, redox potential, carbon, majors and heavy metal solubilized are quantified. However, in most cases, the amounts of matrix and water do not reach the total volume of reactors, leaving some space for air (gaseous phase). Despite this fact, no clear indication is given in standard procedures about the effect of this gaseous phase. Even worse, the gaseous phase is never accounted for when exploiting or modeling ANC data. The gaseous phase may exchange CO2 with the solution, which may, in turn, impact both pH and element release. This study lies within the most general framework for the use of geochemical modeling for the prediction of ANC results for the case of pure phases to real phase assemblages. In this study, we focus on the effect of the gaseous phase on ANC experiments on different mineral phases through geochemical modeling. To do so, we use PHREEQC code to model the evolution of pH and element release (including majors and heavy metals) when several matrices are put in contact with acid or base. We model the following scenarios for the gaseous phase: no gas, contact with the atmosphere (open system

  20. Targeted genetic inactivation of N-acetylglucosaminyltransferase-IVa impairs insulin secretion from pancreatic beta cells and evokes type 2 diabetes.

    PubMed

    Ohtsubo, Kazuaki

    2010-01-01

    The biological significance of protein N-glycosylation has been elucidated using a mouse model bearing a genetic mutation of N-acetylglucosaminyltransferases (GnTs), which initiate the formation of specific branch structures on the mannose core of N-glycans. These glycosylation defects evoked a variety of abnormalities and disorders in specific cell types, tissues, and the whole body, reflecting functional requirements. N-Acetylglucosaminyltransferase-IVa (GnT-IVa) initiates the GlcNAcbeta1-4 branch synthesis on the Manalpha1-3 arm of the N-glycan core thereby increasing N-glycan branch complexity. To investigate the physiological function of GnT-IVa, we engineered and characterized GnT-IVa-deficient mice. GnT-IVa-deficient mice showed a metabolic disorder subsequently diagnosed as type 2 diabetes. In this chapter, methods for characterizing GnT-IVa-deficient mice by physiological analyses to detect metabolic alterations and biochemical analyses using primary isolated pancreatic beta cells are summarized and discussed. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  1. Explorations of new selenites of the group IIIA and IVA metals

    SciTech Connect

    Kong Fang; Li Peicin; Zhang Suyun; Mao Jianggao

    2012-06-15

    Systematic explorations of new phases in the Ga{sup III}/In{sup III}/Ge{sup IV}-Se{sup IV}-O systems by hydrothermal syntheses or solid-state reactions at high-temperature led to six new ternary compounds, namely, M{sub 2}Se{sub 2}O{sub 7} (M=Ga 1, In 2), M(OH)(SeO{sub 3}) (M=Ga 3, In 4), {alpha}-Ge(SeO{sub 3}){sub 2}5 and {beta}-Ge(SeO{sub 3}){sub 2}6. Ga{sub 2}Se{sub 2}O{sub 7}1 displays a 3D open framework composed of 2D gallium oxide layers being further bridged and capped by SeO{sub 3} groups. In{sub 2}Se{sub 2}O{sub 7}2 features a 3D indium oxide framework formed by corner- and edge- sharing InO{sub 6} octahedra with SeO{sub 3} groups attached on the cavities and the 8-member ring tunnels of the structure. The isostructural of M(OH)(SeO{sub 3}) (M=Ga 3, In 4) exhibit a 2D metal selenite layer composed of 1D edge-sharing MO{sub 6} octahedral chains that are interconnected by SeO{sub 3} groups. {alpha}-Ge(SeO{sub 3}){sub 2} (P2{sub 1}/n) 5 displays a 3D open framework with 1D 8-member ring tunnels along the a-axis while {beta}-Ge(SeO{sub 3}){sub 2} (Pa-3) 6 exhibits a condensed 3D network. - Graphical abstract: Highlights: Black-Right-Pointing-Pointer Up to now, selenites of the group IIIA and IVA metals are still rare. Black-Right-Pointing-Pointer Hydrothermal or solid state reactions yielded six new compounds in this system. Black-Right-Pointing-Pointer They are M{sub 2}Se{sub 2}O{sub 7} (M=Ga, In), M(OH)(SeO{sub 3}) (M=Ga, In), {alpha}-Ge(SeO{sub 3}){sub 2} and {beta}-Ge(SeO{sub 3}){sub 2}. Black-Right-Pointing-Pointer They exhibit four different 3D and one 2D structural types. Black-Right-Pointing-Pointer {alpha}-Ge(SeO{sub 3}){sub 2} and {beta}-Ge(SeO{sub 3}){sub 2} represent the first examples of germanium selenites.

  2. Shock-thermal history of Kavarpura IVA iron: Evidences from microtextures and nickel profiling

    NASA Astrophysics Data System (ADS)

    Ray, Dwijesh; Ghosh, S.; Murty, S. V. S.

    2015-11-01

    We classify Kavarpura iron (fell in August, 2006, in Rajasthan, India), an inclusion-free member of high-Ni IVA group. Widmanstätten pattern and finger-cellular plessites textures characteristic of IVA group are present in Kavarpura. Symmetric and asymmetric textural zoning within the cloudy taenite and plessite refer to long term martensitisation process with mean metallographic cooling rate of 200 °C/Ma. Imprints of variable shock pressure domains (Neumann bands and shock hatched ε kamacite) suggest alteration by up to 600 kb shock pressure. Degeneration of cellular plessites, bending of finger plessites and plastic flowage of taenites bear textural evidences corresponding to post-shock annealing which is further confirmed by Ni profiles across the cloudy taenites and plessites under high shock pressure domains. Based on microtextural evidences and Ni profiling, we suggest Kavarpura had cooled at steady state and subsequently suffered multiple impacts.

  3. Molecular Testing of 163 Patients with Morquio A (Mucopolysaccharidosis IVA) Identifies 39 Novel GALNS Mutations

    PubMed Central

    Morrone, A; Tylee, K.L.; Al-Sayed, M; Brusius-Facchin, A.C.; Caciotti, A.; Church, H.J.; Coll, M.J.; Davidson, K.; Fietz, M.J.; Gort, L.; Hegde, M.; Kubaski, F.; Lacerda, L.; Laranjeira, F.; Leistner-Segal, S.; Mooney, S.; Pajares, S.; Pollard, L.; Riberio, I.; Wang, R.Y.; Miller, N.

    2014-01-01

    Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles produce protein with decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided. PMID:24726177

  4. Space Station Freedom airlock - The integration of IVA and EVA capabilities in an orbital element

    NASA Astrophysics Data System (ADS)

    Moore, Thomas O., Jr.; Matthews, Anthony P.

    1992-07-01

    In order to meet mission goals, the Space Station Freedom (SSF) airlock must maximize crew efficiency while supporting a range of extravehicular activity (EVA) and intravehicular activity (IVA) operations. EVA will be a frequently planned occurrence on SSF. In order to maximize the usefulness of the limited EVA resource, overhead times must be minimized. This paper discusses how the SSF airlock outfitting design responds to both IVA and EVA requirements. An overview of the SSF airlock and the missions it must accomplish are also provided. The focus of this paper is on how the outfitting and man systems designs provide solutions to multiple requirements, explicitly stated as well as derived requirements. The Space Station airlock is evaluated as an integrated system in the functional assessments of the EVA task, and this paper explains how station common hardware and systems are adapted to the unique airlock environment.

  5. Thermal histories of IVA iron meteorites from transmission electron microscopy of the cloudy zone microstructure

    NASA Astrophysics Data System (ADS)

    Goldstein, J. I.; Yang, J.; Kotula, P. G.; Michael, J. R.; Scott, E. R. D.

    2009-04-01

    We have measured the size of the high-Ni particles in the cloudy zone and the width of the outer taenite rim in eight low shocked and eight moderately to heavily shocked IVA irons using a transmission electron microscope (TEM). Thin sections for TEM analysis were produced by a focused ion beam instrument. Use of the TEM allowed us to avoid potential artifacts which may be introduced during specimen preparation for SEM analysis of high Ni particles <30 nm in size and to identify microchemical and microstructural changes due to the effects of shock induced reheating. No cloudy zone was observed in five of the eight moderately to highly shocked <13 GPa) IVA irons that were examined in the TEM. Shock induced reheating has allowed for diffusion from 20 nm to 400 nm across kamacite/taenite boundaries, recrystallization of kamacite, and the formation, in Jamestown, of taenite grain boundaries. In the eleven IVA irons with cloudy zone microstructures, the size of the high-Ni particles in the cloudy zone increases directly with increasing bulk Ni content. Our data and the inverse correlation between cooling rate and high-Ni particle size for irons and stony-irons show that IVA cooling rates at 350-200 deg. C are inversely correlated with bulk Ni concentration and vary by a factor of about 15. This cooling rate variation is incompatible with cooling in a metallic core that was insulated with a silicate mantle, but is compatible with cooling in a metallic body of radius 150 +/- 50 km. The widths of the tetrataenite regions next to the cloudy zone correlate directly with high-Ni particle size providing another method to measure low temperature cooling rates.

  6. Natural history and clinical assessment of Taiwanese patients with mucopolysaccharidosis IVA.

    PubMed

    Lin, Hsiang-Yu; Chuang, Chih-Kuang; Chen, Ming-Ren; Chiu, Pao Chin; Ke, Yu-Yuan; Niu, Dau-Ming; Tsai, Fuu-Jen; Hwu, Wuh-Liang; Lin, Ju-Li; Lin, Shuan-Pei

    2014-02-10

    Mucopolysaccharidosis IVA (MPS IVA) is a rare lysosomal storage disorder caused by N-acetylgalactosamine-6-sulfatase deficiency, which catalyzes a step in the catabolism of glycosaminoglycans, keratan sulfate and chondroitin-6-sulfate. This disease has a variable age of onset and rate of progression. A retrospective analysis of medical records of 24 patients with MPS IVA (11 males, 13 females; current mean age ± SD, 12.6 ± 6.6 years; age range, 1.4-29.4 years) seen at 6 medical centers in Taiwan from January 1996 through June 2013 was performed. Mean ages of onset of symptoms and confirmed diagnosis were 2.0 ± 1.6 and 5.7 ± 4.5 years, respectively. The most prevalent clinical manifestations were kyphosis (100%), pectus carinatum (96%), abnormal gait (93%), striking short trunk dwarfism (92%), genu valgum (92%), and valvular heart disease (91%). Eight patients (33%) experienced at least one surgical procedure with the most common being ear tube insertion (25%), adenoidectomy (17%), tonsillectomy (13%), supraglottoplasty (13%), spinal decompression (13%), and spinal fusion (13%). The most prevalent cardiac valve abnormalities were aortic stenosis (45%) and mitral regurgitation (45%). At the time of the study, 8 out of 24 patients (33%) have died at the mean age of 17.2 ± 7.7 years. An understanding of the natural history involved in MPS IVA may allow early diagnosis of the disease. All affected Taiwanese patients experienced significant functional limitations. Adequate evaluations and timely management may improve clinical outcomes and quality of life.

  7. Five novel mutations of GALNS in Korean patients with mucopolysaccharidosis IVA.

    PubMed

    Park, Hyung-Doo; Ko, Ah-Ra; Ki, Chang-Seok; Lee, Soo-Youn; Kim, Jong-Won; Cho, Sung Yoon; Kim, Se Hwa; Park, Sung Won; Sohn, Young Bae; Jin, Dong-Kyu

    2013-03-01

    Mucopolysaccharidosis IVA (MPS IVA; OMIM #253000) is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), a lysosomal enzyme involved in the catabolism of keratan and chondroitin sulfate. In this study, we examined biochemical and genetic data from 6 Korean patients presenting with classic MPS IVA by measuring GALNS activity in peripheral blood leukocytes and skin fibroblasts. We initially identified Korean patients with MPS IVA by clinical, biochemical, and genetic analyses. We performed PCR-direct sequencing to identify molecular defects of the GALNS gene in patients and assessed the mutational statuses of family members as well as 50 healthy unrelated subjects. In silico analyses were performed to check for novel mutations. The mean age of the six female patients was 8.0 ± 5.2 years (range: 2-17 years), and were all found to have severe reductions of GALNS enzyme. A total of 12 mutant alleles were identified, corresponding to 7 different mutations. Five novel mutations were c.218A>G (p.Y73C), c.451C>A (p.P151T), c.725C>G (p.S242C), c.752G>A (p.R251Q), and c.1000C>T (p.Q334X). Two other mutations were c.1156C>T (p.R386C) and c.1243-1G>A. Two mutations, c.451C>A and c.1000C>T, accounted for 58% of all mutations in this sample. Copyright © 2013 Wiley Periodicals, Inc.

  8. Extended surgical resections of advanced thymoma Masaoka stages III and IVa facilitate outcome.

    PubMed

    Ried, Michael; Potzger, Tobias; Sziklavari, Zsolt; Diez, Claudius; Neu, Reiner; Schalke, Berthold; Hofmann, Hans-Stefan

    2014-03-01

    Extended thymoma resections including adjacent structures and pleurectomy/decortication (P/D) with hyperthermic intrathoracic chemotherapy (HITHOC) perfusion were performed in a multidisciplinary treatment regime. Between July 2000 and February 2012, 22 patients with Masaoka stage III (n = 9; 41%) and Masaoka stage IVa (n = 13; 59%) thymic tumors were included. Mean age was 55 years (25-84 years) and 50% (11 out of 22) of patients were female. World Health Organization histological classification was as follows: B2 (n = 15), A (n = 1), B1 (n = 1), B3 (n = 2), and thymic carcinoma (C; n = 3). Radical thymectomy and partial resection of the mediastinal pleura and pericardium were performed. Of the 13, 9 patients with pleural involvement (stage IVa) received radical P/D followed by HITHOC (cisplatin). Macroscopic complete resection (R0/R1) was achieved in 19 (86%) patients. All patients received multimodality treatment depending on tumor stage, histology, and completeness of resection. Thirty-day mortality was 0% and three (13.6%) patients needed operative revision. Recurrence of thymoma was documented in five (22.7%) patients (stage III, n = 1; stage IVa, n = 4). Mean disease-free interval of patients with complete resection (n = 14 out of 22) was 30.2 months. After a mean follow-up of 29 months, 18 out of the 22 (82%) patients are alive. After P/D and HITHOC, 89% (8 out of 9 patients) are alive (current median survival is 25 months) without recurrence. Extended surgical resection of advanced thymic tumors infiltrating adjacent structures (stage III) or with pleural metastases (stage IVa) is safe and feasible. It provides a low recurrence rate and an acceptable survival. Additional HITHOC in patients with pleural thymoma spread seems to offer a better local tumor control. Georg Thieme Verlag KG Stuttgart · New York.

  9. Tests of the Daimler D-IVa Engine at a High Altitude Test Bench

    NASA Technical Reports Server (NTRS)

    Noack, W G

    1920-01-01

    Reports of tests of a Daimler IVa engine at the test-bench at Friedrichshafen, show that the decrease of power of that engine, at high altitudes, was established, and that the manner of its working when air is supplied at a certain pressure was explained. These tests were preparatory to the installation of compressors in giant aircraft for the purpose of maintaining constant power at high altitudes.

  10. Mucopolysaccharidosis type IVA: evidence of primary and secondary central nervous system involvement.

    PubMed

    Borlot, Felippe; Arantes, Paula Ricci; Quaio, Caio Robledo; Franco, José Francisco da Silva; Lourenço, Charles Marques; Gomy, Israel; Bertola, Debora Romeo; Kim, Chong Ae

    2014-05-01

    Mucopolysaccharidosis type IVA is a rare lysosomal storage disease caused by a deficiency of N-acetylgalactosamine 6-sulfatase. Studies usually focus on skeletal abnormalities and their consequences. This study explores the neurological manifestations in a cohort of mucopolysaccharidosis type IVA patients, with a detailed focus on brain and spinal magnetic resonance imaging (MRI) findings. We performed a cross-sectional study involving nine patients with a biochemical confirmation of mucopolysaccharidosis type IVA. The protocol consists of a comprehensive clinical examination and brain and spinal cord MRI analysis for all subjects. The mean age was 16.4 years (±5.7) and the mean onset of symptoms was 11.5 months (±6.3). Overall, cognition was spared in all but one patient and motor weakness was a constant finding in all patients. Deep sensation impairment was found in six patients. The brain MRIs showed non-specific white matter changes in two patients. Other abnormalities such as clival hypoplasia, basilar invagination, and arachnoid cists appeared in seven of the nine patients. Eight patients presented spinal cord compression, and in three of them, two spinal levels were compromised. Odontoid hypoplasia and degenerative features in the neuroaxis were present in all patients. Our experience with mucopolysaccharidosis type IVA patients supports the evidence of central nervous system involvement. We emphasize the importance of regular clinical assessments with complete MRI studies, as an attempt to detect the early signs of spinal cord compression. This evaluation may be especially important before surgical interventions, as occult lesions may become symptomatic and promote postoperative unfavorable outcomes. © 2014 Wiley Periodicals, Inc.

  11. Aib and iva in the biosphere: neither rare nor necessarily extraterrestrial.

    PubMed

    Brückner, Hans; Becker, Dieter; Gams, Walter; Degenkolb, Thomas

    2009-01-01

    Fourty-nine species and strains of filamentous fungi of the genera Acremonium, Bionectria, Clonostachys, Emericellopsis, Hypocrea/Trichoderma, Lecythophora, Monocillium, Nectriopsis, Niesslia, Tolypocladium, and Wardomyces, deposited with the culture collection of the Centraalbureau voor Schimmelcultures (CBS) in Utrecht, The Netherlands, were grown on nutrient agar plates. Organic extracts of mycelia were analyzed after acidic total hydrolysis and derivatization by GC/SIM-MS on Chirasil-L-Val for the presence of Aib (=alpha-aminoisobutyric acid, 2-methylalanine) and DL-Iva (=isovaline, 2-ethylalanine). In 37 of the hydrolysates, Aib was detected, and in several of them D-Iva or mixtures of D- and L-Iva. Non-proteinogenic Aib, in particular, is a highly specific marker for a distinctive group of fungal polypeptides named peptaibols or, comprehensively, peptaibiotics, i.e., peptides containing Aib and displaying (anti)biotic activities. The biotic synthesis of these amino acids by filamentous fungi contradicts the still widespread belief that alpha,alpha-dialkyl-alpha-amino acids do not or rarely occur in the biosphere and, if detected, are of extraterrestrial origin. The abundant production of peptaibiotics by cosmopolitan species of microfungi has also to be considered in the discussion on the occurrence of Aib and Iva in ancient and recent sediments. The detection of trace amounts of Aib in ice samples of Antarctica that are devoid of meteorites might also be related to the presence of Aib-producing microorganisms, being either indigenous psychrophiles, or being transported and localized by mechanisms related to bioaerosols and cryoconites. The presence of microfungi being capable of producing alpha,alpha-dialkyl alpha-amino acids in terrestrial samples, and possible contamination of extraterrestrial materials are pointed out to be of relevance for the reliable interpretation of cosmogeochemical data.

  12. Comparison of reporting phase I trial results in ClinicalTrials.gov and matched publications.

    PubMed

    Shepshelovich, D; Goldvaser, H; Wang, L; Abdul Razak, A R; Bedard, P L

    2017-09-14

    Background Data on completeness of reporting of phase I cancer clinical trials in publications are lacking. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching primary publications published prior to November 1, 2016. Reporting in primary publications was compared with the ClinicalTrials.gov database using a 28-point score (2=complete; 1=partial; 0=no reporting) for 14 items related to study design, outcome measures and safety profile. Inconsistencies between primary publications and ClinicalTrials.gov were recorded. Linear regression was used to identify factors associated with incomplete reporting. Results After a review of 583 trials in ClinicalTrials.gov , 163 matching primary publications were identified. Publications reported outcomes that did not appear in ClinicalTrials.gov in 25% of trials. Outcomes were upgraded, downgraded or omitted in publications in 47% of trials. The overall median reporting score was 23/28 (interquartile range 21-25). Incompletely reported items in >25% publications were: inclusion criteria (29%), primary outcome definition (26%), secondary outcome definitions (53%), adverse events (71%), serious adverse events (80%) and dates of study start and database lock (91%). Higher reporting scores were associated with phase I (vs phase I/II) trials (p<0.001), multicenter trials (p<0.001) and publication in journals with lower impact factor (p=0.004). Conclusions Reported results in primary publications for early phase cancer trials are frequently inconsistent or incomplete compared with ClinicalTrials.gov entries. ClinicalTrials.gov may provide more comprehensive data from new cancer drug trials.

  13. INL Results for Phases I and III of the OECD/NEA MHTGR-350 Benchmark

    SciTech Connect

    Gerhard Strydom; Javier Ortensi; Sonat Sen; Hans Hammer

    2013-09-01

    The Idaho National Laboratory (INL) Very High Temperature Reactor (VHTR) Technology Development Office (TDO) Methods Core Simulation group led the construction of the Organization for Economic Cooperation and Development (OECD) Modular High Temperature Reactor (MHTGR) 350 MW benchmark for comparing and evaluating prismatic VHTR analysis codes. The benchmark is sponsored by the OECD's Nuclear Energy Agency (NEA), and the project will yield a set of reference steady-state, transient, and lattice depletion problems that can be used by the Department of Energy (DOE), the Nuclear Regulatory Commission (NRC), and vendors to assess their code suits. The Methods group is responsible for defining the benchmark specifications, leading the data collection and comparison activities, and chairing the annual technical workshops. This report summarizes the latest INL results for Phase I (steady state) and Phase III (lattice depletion) of the benchmark. The INSTANT, Pronghorn and RattleSnake codes were used for the standalone core neutronics modeling of Exercise 1, and the results obtained from these codes are compared in Section 4. Exercise 2 of Phase I requires the standalone steady-state thermal fluids modeling of the MHTGR-350 design, and the results for the systems code RELAP5-3D are discussed in Section 5. The coupled neutronics and thermal fluids steady-state solution for Exercise 3 are reported in Section 6, utilizing the newly developed Parallel and Highly Innovative Simulation for INL Code System (PHISICS)/RELAP5-3D code suit. Finally, the lattice depletion models and results obtained for Phase III are compared in Section 7. The MHTGR-350 benchmark proved to be a challenging simulation set of problems to model accurately, and even with the simplifications introduced in the benchmark specification this activity is an important step in the code-to-code verification of modern prismatic VHTR codes. A final OECD/NEA comparison report will compare the Phase I and III results

  14. Structure of the Type IVa Major Pilin from the Electrically Conductive Bacterial Nanowires of Geobacter sulfurreducens

    SciTech Connect

    Reardon, Patrick N.; Mueller, Karl T.

    2013-10-11

    Several species of bacteria are capable of reducing insoluble metal oxides as well as other extracellular electron acceptors. These bacteria play a critical role in the cycling of minerals in subsurface environments, sediments, and groundwater. In some species of bacteria, such as Geobacter sulfurreducens, the transport of electrons is facilitated by filamentous fibers that are referred to as bacterial nanowires. These nanowires belong to the type IVa family of pilin proteins and are mainly comprised of one subunit protein, PilA. Here, we report the high resolution solution nuclear magnetic resonance (NMR) structure of the PilA protein from G. sulfurreducens determined in detergent micelles. The protein is over 85% α-helical and exhibits similar architecture to the N-terminal regions of other non-conductive type IVa pilins. The detergent micelle interacts with the first 21 amino acids of the protein, indicating that this region likely associates with the bacterial inner membrane prior to fiber formation. A model of the G. sulfurreducens pilus fiber is proposed based on docking of this structure into the fiber model of the type IVa pilin from Neisseria gonorrhoeae. This model provides insight into the organization of aromatic amino acids that are important for electrical conduction.

  15. IVA cloning: A single-tube universal cloning system exploiting bacterial In Vivo Assembly

    PubMed Central

    García-Nafría, Javier; Watson, Jake F.; Greger, Ingo H.

    2016-01-01

    In vivo homologous recombination holds the potential for optimal molecular cloning, however, current strategies require specialised bacterial strains or laborious protocols. Here, we exploit a recA-independent recombination pathway, present in widespread laboratory E.coli strains, to develop IVA (In Vivo Assembly) cloning. This system eliminates the need for enzymatic assembly and reduces all molecular cloning procedures to a single-tube, single-step PCR, performed in <2 hours from setup to transformation. Unlike other methods, IVA is a complete system, and offers significant advantages over alternative methods for all cloning procedures (insertions, deletions, site-directed mutagenesis and sub-cloning). Significantly, IVA allows unprecedented simplification of complex cloning procedures: five simultaneous modifications of any kind, multi-fragment assembly and library construction are performed in approximately half the time of current protocols, still in a single-step fashion. This system is efficient, seamless and sequence-independent, and requires no special kits, enzymes or proprietary bacteria, which will allow its immediate adoption by the academic and industrial molecular biology community. PMID:27264908

  16. Effects of eicosapentaenoic acid on peri-procedural (type IVa) myocardial infarction following elective coronary stenting.

    PubMed

    Kurita, Akiyoshi; Takashima, Hiroaki; Ando, Hirohiko; Kumagai, Soichiro; Waseda, Katsuhisa; Gosho, Masahiko; Amano, Tetsuya

    2015-08-01

    The aim of this study was to assess the effect of eicosapentaenoic acid (EPA) on peri-procedural (type IVa) myocardial infarction (MI) following elective percutaneous coronary intervention (PCI). We analyzed data from 165 of 178 consecutive patients with stable angina pectoris who underwent de novo successful stent implantation in the native coronary artery. Patients were assigned to receive statin therapy in combination with 1800mg/day of EPA or statin alone. Post-procedural index of microcirculatory resistance (IMR) values were calculated for 30 patients in the EPA group and 32 controls. In the multivariate logistic model, EPA administration, low kidney function, and the presence of slow flow/no reflow were significantly and independently associated with type IVa MI. Post-procedural IMR values were significantly lower in the EPA group [19.8 (6.4, 51.1) vs. 27.8 (8.2, 89.3), p=0.003] compared to the control group. Pre-treatment with EPA in addition to statins significantly reduced the incidence of type IVa MI compared to statin therapy only, which may be attributed to the ability of EPA to reduce microvascular dysfunction induced by PCI. Copyright © 2014. Published by Elsevier Ltd.

  17. IVA cloning: A single-tube universal cloning system exploiting bacterial In Vivo Assembly.

    PubMed

    García-Nafría, Javier; Watson, Jake F; Greger, Ingo H

    2016-06-06

    In vivo homologous recombination holds the potential for optimal molecular cloning, however, current strategies require specialised bacterial strains or laborious protocols. Here, we exploit a recA-independent recombination pathway, present in widespread laboratory E.coli strains, to develop IVA (In Vivo Assembly) cloning. This system eliminates the need for enzymatic assembly and reduces all molecular cloning procedures to a single-tube, single-step PCR, performed in <2 hours from setup to transformation. Unlike other methods, IVA is a complete system, and offers significant advantages over alternative methods for all cloning procedures (insertions, deletions, site-directed mutagenesis and sub-cloning). Significantly, IVA allows unprecedented simplification of complex cloning procedures: five simultaneous modifications of any kind, multi-fragment assembly and library construction are performed in approximately half the time of current protocols, still in a single-step fashion. This system is efficient, seamless and sequence-independent, and requires no special kits, enzymes or proprietary bacteria, which will allow its immediate adoption by the academic and industrial molecular biology community.

  18. Structure of the type IVa major pilin from the electrically conductive bacterial nanowires of Geobacter sulfurreducens.

    PubMed

    Reardon, Patrick N; Mueller, Karl T

    2013-10-11

    Several species of δ proteobacteria are capable of reducing insoluble metal oxides as well as other extracellular electron acceptors. These bacteria play a critical role in the cycling of minerals in subsurface environments, sediments, and groundwater. In some species of bacteria such as Geobacter sulfurreducens, the transport of electrons is proposed to be facilitated by filamentous fibers that are referred to as bacterial nanowires. These nanowires are polymeric assemblies of proteins belonging to the type IVa family of pilin proteins and are mainly comprised of one subunit protein, PilA. Here, we report the high resolution solution NMR structure of the PilA protein from G. sulfurreducens determined in detergent micelles. The protein is >85% α-helical and exhibits similar architecture to the N-terminal regions of other non-conductive type IVa pilins. The detergent micelle interacts with the first 21 amino acids of the protein, indicating that this region likely associates with the bacterial inner membrane prior to fiber formation. A model of the G. sulfurreducens pilus fiber is proposed based on docking of this structure into the fiber model of the type IVa pilin from Neisseria gonorrhoeae. This model provides insight into the organization of aromatic amino acids that are important for electrical conduction.

  19. SMOS L1PP Performance Analysis from Commissioning Phase - Improved Algorithms and Major Results

    NASA Astrophysics Data System (ADS)

    Castro, Rita; Oliva, Roger; Gutiérrez, Antonio; Barbosa, José; Catarino, Nuno; Martin-Neira, Manuel; Zundo, Michele; Cabot, François

    2010-05-01

    Following the Soil Moisture and Ocean Salinity (SMOS) launch in November 2009, a Commissioning Phase has taken place for six months, having Deimos closely cooperated with the European Space Agency's (ESA) Level 1 team. During these six months several studies have been conducted on calibration optimization, image reconstruction improvement, geolocation assessment and the impact on scientific results, in particular to insure optimal input to Level 2 Soil Moisture and Ocean Salinity retrieval. In parallel with the scientific studies, some new algorithms/mitigation techniques had to be developed, tested and implemented during the Commissioning Phase. Prior to launch, the Level 1 Prototype Processor (L1PP) included already several experimental algorithms different from the ones existent in the operational chain. These algorithms were tested during Commissioning and some were included in the final processing baseline as a result of the planned studies. Some unforeseen algorithms had to be defined, implemented and tested during the Commissioning Phase itself and these will also be described below. In L1a, for example, the calibration of the Power Measuring Systems (PMS) can be done using a cold target as reference, i.e., the Sky at ~3 K. This has been extensively analyzed and the results will be presented here. At least two linearity corrections to the PMS response function have been tested and compared. The deflection method was selected for inclusion on the operational chain and the results leading to this decision will be also presented. In Level 1B, all the foreign sources algorithms have been tested and validated using real data. The System Response Function (G-matrix) computed for different events has been analyzed and criteria for validation of its pseudo inverse, the J+ matrix, have been defined during the Commissioning Phase. The impact of errors in the J+ matrix has been studied and well characterized. The effects of the Flat Target Response (FTR) have also been

  20. Preliminary results of the large experimental wind turbine phase of the national wind energy program

    NASA Technical Reports Server (NTRS)

    Thomas, R. L.; Sholes, J. E.

    1975-01-01

    A major phase of the wind energy program is the development of reliable wind turbines for supplying cost-competitive electrical energy. This paper discusses the preliminary results of two projects in this phase of the program. First an experimental 100 kW wind turbine design and its status are reviewed. Also discussed are the results of two parallel design studies for determining the configurations and power levels for wind turbines with minimum energy costs. These studies show wind energy costs of 7 to 1.5 c/kWH for wind turbines produced in quantities of 100 to 1000 a year and located at sites having average winds of 12 to 18 mph.

  1. Tanker Avionics/Aircrew Complement Evaluation (TAACE). Phase 0. Analysis and Mockup. Volume I. Results.

    DTIC Science & Technology

    1980-05-01

    AIRCREW COMPLEMENT EVALUATION (TAACE) PHASE 0 - ANALYSIS AND MOCKUP C) VOLUME I: RESULTS !x The Bunker Ramo Corporation - Electronic Systems Division...data, is not to be re- garded by implication or otherwise as in any manner licensing the holder or any other person or corporation , or conveying any...adro Iftj William Ret randt - A./Sexton ( 10. PROGRAM ELEMENT.P E T. TASK Bunker Ramo, Corporation 4130 Linden Ave. 112 Dayton, Ohio 45432

  2. 45 CFR 233.145 - Expiration of medical assistance programs under titles I, IV-A, X, XIV and XVI of the Social...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... titles I, IV-A, X, XIV and XVI of the Social Security Act. 233.145 Section 233.145 Public Welfare... FINANCIAL ASSISTANCE PROGRAMS § 233.145 Expiration of medical assistance programs under titles I, IV-A, X..., enacted July 30, 1965, no payment may be made to any State under title I, IV-A, X, XIV or XVI of...

  3. 45 CFR 233.145 - Expiration of medical assistance programs under titles I, IV-A, X, XIV and XVI of the Social...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... titles I, IV-A, X, XIV and XVI of the Social Security Act. 233.145 Section 233.145 Public Welfare... FINANCIAL ASSISTANCE PROGRAMS § 233.145 Expiration of medical assistance programs under titles I, IV-A, X..., enacted July 30, 1965, no payment may be made to any State under title I, IV-A, X, XIV or XVI of...

  4. 45 CFR 233.145 - Expiration of medical assistance programs under titles I, IV-A, X, XIV and XVI of the Social...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... titles I, IV-A, X, XIV and XVI of the Social Security Act. 233.145 Section 233.145 Public Welfare... FINANCIAL ASSISTANCE PROGRAMS § 233.145 Expiration of medical assistance programs under titles I, IV-A, X..., enacted July 30, 1965, no payment may be made to any State under title I, IV-A, X, XIV or XVI of...

  5. Cage occupancy and structural changes during hydrate formation from initial stages to resulting hydrate phase.

    PubMed

    Schicks, Judith M; Luzi-Helbing, Manja

    2013-11-01

    Hydrate formation processes and kinetics are still not sufficiently understood on a molecular level based on experimental data. In particular, the cavity formation and occupancy during the initial formation and growth processes of mixed gas hydrates are rarely investigated. In this study, we present the results of our time-depending Raman spectroscopic measurements during the formation of hydrates from ice and gases or gas mixtures such as CH4, CH4-CO2, CH4-H2S, CH4-C3H8, CH4-iso-C4H10, and CH4-neo-C5H12 at constant pressure and temperature conditions and constant composition of the feed gas phase. All investigated systems in this study show the incorporation of CH4 into the 5(12) cavities as first step in the initial stages of hydrate formation. Furthermore, the results imply that the initial hydrate phases differ from the resulting hydrate phase having reached a steady state regarding the occupancy and ratio of the small and large cavities of the hydrate.

  6. Water quality monitoring of Sweetwater and Loveland reservoirs--Phase one results 1998-1999

    USGS Publications Warehouse

    Majewski, Michael S.; Sidhu, Jagdeep S.; Mendez, Gregory O.

    2002-01-01

    In 1998, the U.S. Geological Survey began a study to assess the overall health of the watershed feeding the Sweetwater Reservoir in southern San Diego County, California. The study focussed on monitoring for organic chemical contamination and the effects of construction and operation of State Route 125 on water quality. Three environmental compartments (air, water, and bed sediments) are being sampled regularly for chemical contaminants, including volatile organic compounds, polynuclear aromatic hydrocarbons, polychlorinated biphenyls, pesticides, and major and trace elements. The study is divided into two phases. Phase I sampling is designed to establish baseline conditions for target compounds in terms of detection frequency and concentration in air, water, and bed sediments. Phase II sampling will continue at the established monitoring sites during and after construction of State Route 125 to assess chemical impact on water quality in the reservoir resulting from land-use changes and development in the watershed. This report describes the study design, the sampling and analytical methods, and presents the data results for the first year of the study, September 1998 to September 1999.

  7. Cyclic Cushing's disease with misleading inferior petrosal sinus sampling results during a trough phase.

    PubMed

    Bonert, Vivien; Bose, Namrata; Carmichael, John D

    2015-02-01

    Diagnosing Cushing's syndrome is challenging and is further hampered when investigations are performed in a patient with cyclic Cushing's syndrome. A subset of patients with Cushing's syndrome exhibit periods of abnormal cortisol secretion with interspersed normal secretion. Patients can have periods of clinical improvement during these quiescent phases or remain symptomatic. Initial diagnostic testing can be challenging because of the unpredictable durations of the peak and trough phases, and it is especially challenging when the diagnosis of cyclic Cushing's syndrome has not yet been determined. Here, the authors present the case of a patient with Cushing's disease with a pathology-proven adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma and whose initial inferior petrosal sinus sampling (IPSS) results were deemed indeterminate; further studies elucidated the diagnosis of cyclic Cushing's syndrome. Repeat IPSS was diagnostic of a central source for ACTH secretion, and the patient was treated successfully with transsphenoidal resection. Literature concerning the diagnosis and management of cyclic Cushing's syndrome is also reviewed.

  8. Preliminary results of the large experimental wind turbine phase of the national wind energy program

    NASA Technical Reports Server (NTRS)

    Thomas, R. L.; Sholes, T.; Sholes, J. E.

    1975-01-01

    The preliminary results of two projects in the development phase of reliable wind turbines designed to supply cost-competitive electrical energy were discussed. An experimental 100 kW wind turbine design and its status are first reviewed. The results of two parallel design studies for determining the configurations and power levels for wind turbines with minimum energy costs are also discussed. These studies predict wind energy costs of 1.5 to 7 cents per kW-h for wind turbines produced in quantities of 100 to 1000 per year and located at sites having average winds of 12 to 18 mph.

  9. MD-2 Residues Tyrosine 42, Arginine 69, Aspartic Acid 122, and Leucine 125 Provide Species Specificity for Lipid IVA*

    PubMed Central

    Meng, Jianmin; Drolet, Joshua R.; Monks, Brian G.; Golenbock, Douglas T.

    2010-01-01

    Lipopolysaccharide (LPS) activates the innate immune response through the Toll-like receptor 4 (TLR4)·MD-2 complex. A synthetic lipid A precursor, lipid IVA, induces an innate immune response in mice but not in humans. Both TLR4 and MD-2 are required for the agonist activity of lipid IVA in mice, with TLR4 interacting through specific surface charges at the dimerization interface. In this study, we used site-directed mutagenesis to identify the MD-2 residues that determine lipid IVA species specificity. A single mutation of murine MD-2 at the hydrophobic pocket entrance, E122K, substantially reduced the response to lipid IVA. Combining the murine MD-2 E122K with the murine TLR4 K367E/S386K/R434Q mutations completely abolished the response to lipid IVA, effectively converting the murine cellular response to a human-like response. In human cells, however, simultaneous mutations of K122E, K125L, Y41F, and R69G on human MD-2 were required to promote a response to lipid IVA. Combining the human MD-2 quadruple mutations with the human TLR4 E369K/Q436R mutations completely converted the human MD-2/human TLR4 receptor to a murine-like receptor. Because MD-2 residues 122 and 125 reside at the dimerization interface near the pocket entrance, surface charge differences here directly affect receptor dimerization. In comparison, residues 42 and 69 reside at the MD-2/TLR4 interaction surface opposite the dimerization interface. Surface charge differences there likely affect the binding angle and/or rigidity between MD-2 and TLR4, exerting an indirect influence on receptor dimerization and activation. Thus, surface charge differences at the two MD-2/TLR4 interfaces determine the species-specific activation of lipid IVA. PMID:20592019

  10. MD-2 residues tyrosine 42, arginine 69, aspartic acid 122, and leucine 125 provide species specificity for lipid IVA.

    PubMed

    Meng, Jianmin; Drolet, Joshua R; Monks, Brian G; Golenbock, Douglas T

    2010-09-03

    Lipopolysaccharide (LPS) activates the innate immune response through the Toll-like receptor 4 (TLR4).MD-2 complex. A synthetic lipid A precursor, lipid IV(A), induces an innate immune response in mice but not in humans. Both TLR4 and MD-2 are required for the agonist activity of lipid IV(A) in mice, with TLR4 interacting through specific surface charges at the dimerization interface. In this study, we used site-directed mutagenesis to identify the MD-2 residues that determine lipid IV(A) species specificity. A single mutation of murine MD-2 at the hydrophobic pocket entrance, E122K, substantially reduced the response to lipid IV(A). Combining the murine MD-2 E122K with the murine TLR4 K367E/S386K/R434Q mutations completely abolished the response to lipid IV(A), effectively converting the murine cellular response to a human-like response. In human cells, however, simultaneous mutations of K122E, K125L, Y41F, and R69G on human MD-2 were required to promote a response to lipid IV(A). Combining the human MD-2 quadruple mutations with the human TLR4 E369K/Q436R mutations completely converted the human MD-2/human TLR4 receptor to a murine-like receptor. Because MD-2 residues 122 and 125 reside at the dimerization interface near the pocket entrance, surface charge differences here directly affect receptor dimerization. In comparison, residues 42 and 69 reside at the MD-2/TLR4 interaction surface opposite the dimerization interface. Surface charge differences there likely affect the binding angle and/or rigidity between MD-2 and TLR4, exerting an indirect influence on receptor dimerization and activation. Thus, surface charge differences at the two MD-2/TLR4 interfaces determine the species-specific activation of lipid IV(A).

  11. Compassion satisfaction, compassion fatigue, anxiety, depression and stress in registered nurses in Australia: phase 2 results.

    PubMed

    Drury, Vicki; Craigie, Mark; Francis, Karen; Aoun, Samar; Hegney, Desley G

    2014-05-01

    This is the first two-phase Australian study to explore the factors impacting upon compassion satisfaction, compassion fatigue, anxiety, depression and stress and to describe the strategies nurses use to build compassion satisfaction into their working lives. Compassion fatigue has been found to impact on job satisfaction, the quality of patient care and retention within nursing. This study provides new knowledge on the influences of anxiety, stress and depression and how they relate to compassion satisfaction and compassion fatigue. In Phase 2 of the study, 10 nurses from Phase 1 of the study participated in individual interviews and a focus group. A semi-structured interview schedule guided the conversations with the participants. Data analysis resulted in seven main themes: social networks and support;infrastructure and support; environment and lifestyle; learning; leadership; stress; and suggestions to build psychological wellness in nurses. Findings suggest that a nurse’s capacity to cope is enhanced through strong social and collegial support, infrastructure that supports the provision of quality nursing care and positive affirmation. These concepts are strongly linked to personal resilience. for nursing management These findings support the need for management to develop appropriate interventions to build resilience in nurses.

  12. Mid-term results of Oxford Phase 3 unicompartmental knee arthroplasty in obese patients.

    PubMed

    Cepni, Serdar Kamil; Arslan, Armağan; Polat, Halil; Yalçin, Atilla; Parmaksizoğlu, Atilla Sancar

    2014-01-01

    The aim of this study was to evaluate the mid-term outcomes of Oxford Phase 3 unicompartmental knee arthroplasty (UKA) in obese patients in terms of prosthesis survival, progression of lateral compartment arthrosis and functional outcomes. The study included 67 patients, with a body mass index over 30, treated with mobile bearing Oxford Phase 3 UKA for isolated medial osteoarthritis between January 2005 and December 2010. Preoperative and postoperative knee range of motion (ROM) and knee scores (Hospital for Special Surgery, HSS and Oxford knee scores) were compared. Additionally, prostheses were evaluated using Oxford radiographic evaluation criteria at the final follow-up. Mean age was 61 years and mean follow-up was 67.5 months. Insert dislocation occurred in 3 patients (4.5%). Postoperative knee ROM, HSS and Oxford knee scores were significantly improved (p<0.05). There was no sign of prosthesis failure or lateral compartment arthrosis in radiographic evaluation at the final follow-up. Oxford Phase 3 UKA with mobile bearing has good mid-term results in obese patients over 60 years of age.

  13. Fluorimetric Assays for N-Acetylgalactosamine-6-Sulfatase and Arylsulfatase B Based on the Natural Substrates for Confirmation of Mucopolysaccharidoses Types IVA and VI

    PubMed Central

    Kumar, Arun Babu; Spacil, Zdenek; Ghomashchi, Farideh; Masi, Sophia; Sumida, Tomomi; Ito, Makoto; Turecek, Frantisek; Scott, C. Ronald; Gelb, Michael H.

    2015-01-01

    Background Treatments have been developed for mucopolysaccharidoses-IVA (MPS-IVA) and MPS-VI suggesting the need for eventual newborn screening. Biochemical enzyme assays are important for diagnosis. Previously reported fluorimetric assays of the relevant enzymes are based on substrates with poor activity or specificity. Methods We developed new fluorimetric assays for N-acetylgalactosamine-6-sulfatase (GALNS) and arylsulfatase B (ARSB) based on the natural substrates, N-acetylgalactosamine-6-sulfate (and 4-sulfate), which have improved activity and specificity toward the relevant enzymes. The new substrates were tested on dried blood spots on newborn screening cards, and assays showed acceptable linearity in response with the amount of enzyme present (using quality control samples). Results When tested on dried blood spots from random newborns and affected patients, the assays showed good discrimination between the 2 sample groups. Conclusions The analytical range of the new fluorimetric assays, defined as the ratio of enzyme-dependent-to-enzyme-independent assay response, is likely to be insufficient to use these assays for newborn screening. Rather, these new fluorimetric assays should be useful in a diagnostic lab to confirm a diagnosis via biochemical enzyme testing. PMID:26282597

  14. Bevacizumab, Oxaliplatin, and Capecitabine With Radiation Therapy in Rectal Cancer: Phase I Trial Results

    SciTech Connect

    Czito, Brian G. . E-mail: czito001@mc.duke.edu; Bendell, Johanna C.; Willett, Christopher G.; Morse, Michael A.; Blobe, Gerard C.; Tyler, Douglas S.; Thomas, John; Ludwig, Kirk A.; Mantyh, Christopher R.; Ashton, Jill; Yu Daohai; Hurwitz, Herbert I.

    2007-06-01

    Purpose: The overexpression of vascular endothelial growth factor (VEGF) is associated with poor outcomes in colorectal cancer patients. Bevacizumab, a VEGF inhibitor, enhances the effects of chemotherapy and radiation therapy on tumor cytotoxicity in preclinical models, including colorectal cancer. A Phase I trial was undertaken to evaluate the combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in patients with rectal cancer. Methods and Materials: Patients with pathologically confirmed adenocarcinoma of the rectum were eligible. Pretreatment staging included computerized tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external beam radiation therapy (EBRT) to the tumor in 28 fractions. Capecitabine, oxaliplatin, and bevacizumab were administered concurrently with radiation therapy. After EBRT completion, patients were restaged and evaluated for surgery. Primary endpoints included the determination of dose-limiting toxicity and a recommended Phase II dose, non dose-limiting toxicity, and preliminary radiographic and pathologic response rates. Results: Eleven patients were enrolled. All were evaluable for toxicity and efficacy. Dose level 2 was associated with unacceptable toxicity (primarily diarrhea). Dose level 1 had an acceptable toxicity profile. The recommended Phase II dose in our study was bevacizumab 15 mg/kg Day 1 + 10 mg/kg Days 8 and 22, oxaliplatin 50 mg/m{sup 2} weekly, and capecitabine 625 mg/m{sup 2} bid during radiation days. Six patients had clinical responses. Two patients had a pathologic complete response, and 3 had microscopic disease only. One patient experienced a postoperative abscess, one a syncopal episode during adjuvant chemotherapy, and one a subclinical myocardial infarction during adjuvant chemotherapy. Conclusions: The combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in rectal cancer was tolerable, with encouraging response rates. Further

  15. Development of Magnetic Materials Based on the Ordered Fe50Ni50 Phase: Methodologies and Results

    NASA Astrophysics Data System (ADS)

    Poirier, Eric; Tessema, Misle M.; Meyer, Martin S.; Pinkerton, Frederick E.

    2013-03-01

    The L10 FeNi structure known as tetrataenite, usually found in meteorites, is reported to possess significant magnetocrystalline anisotropy suitable for hard magnetic properties. As part of the ongoing Advanced Research Project Agency-Energy project on FeNi-based magnets, melt-spinning was used to synthesize new FeNi precursors. The melt-spinning conditions were established in terms of wheel speed, ejection pressure, and atmosphere composition and pressure. The as-spun ribbons have a cubic crystal structure with a =3.584 +/- 0.002 Å, and (100) preferred grain orientation perpendicular to the ribbon. They also behave like soft magnetic materials, with coercitivities below 0.3 kOe. DSC response curves were essentially featureless, except for a thermal signature at about 515 °C associated with the Curie temperature. In contrast, melt-spun FeNi ribbons that were subsequently ball-milled and annealed exhibited a more complex thermal behavior compared to the as-spun ribbons with a weak endotherm in the 300-350 °C range followed by an exotherm at higher temperatures. These results are discussed in the context of a search for an order-disorder phase transition associated with the L10 phase, and preferred properties for permanent magnet applications. Although L10 phase formation was not observed at this point, the techniques established for processing FeNi will be further studied on modified FeNi alloys as a promising route to obtain the L10 phase. This work is supported by ARPA-E REACT Grant # 0472-1537.

  16. Sentinel-2A image quality commissioning phase final results: geometric calibration and performances

    NASA Astrophysics Data System (ADS)

    Languille, F.; Gaudel, A.; Dechoz, C.; Greslou, D.; de Lussy, F.; Trémas, T.; Poulain, V.; Massera, S.

    2016-10-01

    In the frame of the Copernicus program of the European Commission, Sentinel-2 offers multispectral high-spatial-resolution optical images over global terrestrial surfaces. In cooperation with ESA, the Centre National d'Etudes Spatiales (CNES) is in charge of the image quality of the project, and so ensures the CAL/VAL commissioning phase during the months following the launch. Sentinel-2 is a constellation of 2 satellites on a polar sun-synchronous orbit with a revisit time of 5 days (with both satellites), a high field of view - 290km, 13 spectral bands in visible and shortwave infrared, and high spatial resolution - 10m, 20m and 60m. The Sentinel-2 mission offers a global coverage over terrestrial surfaces. The satellites acquire systematically terrestrial surfaces under the same viewing conditions in order to have temporal images stacks. The first satellite was launched in June 2015. Following the launch, the CAL/VAL commissioning phase is then lasting during 6 months for geometrical calibration. This paper will point on observations and results seen on Sentinel-2 images during commissioning phase. It will provide explanations about Sentinel-2 products delivered with geometric corrections. This paper will detail calibration sites, and the methods used for geometrical parameters calibration and will present linked results. The following topics will be presented: viewing frames orientation assessment, focal plane mapping for all spectral bands, results on geolocation assessment, and multispectral registration. There is a systematic images recalibration over a same reference which is a set of S2 images produced during the 6 months of CAL/VAL. This set of images will be presented as well as the geolocation performance and the multitemporal performance after refining over this ground reference.

  17. OECD/NEA Burnup Credit Calculational Criticality Benchmark Phase I-B Results

    SciTech Connect

    DeHart, M.D.

    1993-01-01

    Burnup credit is an ongoing technical concern for many countries that operate commercial nuclear power reactors. In a multinational cooperative effort to resolve burnup credit issues, a Burnup Credit Working Group has been formed under the auspices of the Nuclear Energy Agency of the Organization for Economic Cooperation and Development. This working group has established a set of well-defined calculational benchmarks designed to study significant aspects of burnup credit computational methods. These benchmarks are intended to provide a means for the intercomparison of computer codes, methods, and data applied in spent fuel analysis. The benchmarks have been divided into multiple phases, each phase focusing on a particular feature of burnup credit analysis. This report summarizes the results and findings of the Phase I-B benchmark, which was proposed to provide a comparison of the ability of different code systems and data libraries to perform depletion analysis for the prediction of spent fuel isotopic concentrations. Results included here represent 21 different sets of calculations submitted by 16 different organizations worldwide, and are based on a limited set of nuclides determined to have the most important effect on the neutron multiplication factor of light-water-reactor spent fuel. A comparison of all sets of results demonstrates that most methods are in agreement to within 10% in the ability to estimate the spent fuel concentrations of most actinides. All methods are within 11% agreement about the average for all fission products studied. Furthermore, most deviations are less than 10%, and many are less than 5%. The exceptions are {sup 149}Sm, {sup 151}Sm, and {sup 155}Gd.

  18. OECD/NEA burnup credit calculational criticality benchmark Phase I-B results

    SciTech Connect

    DeHart, M.D.; Parks, C.V.; Brady, M.C.

    1996-06-01

    In most countries, criticality analysis of LWR fuel stored in racks and casks has assumed that the fuel is fresh with the maximum allowable initial enrichment. This assumption has led to the design of widely spaced and/or highly poisoned storage and transport arrays. If credit is assumed for fuel burnup, initial enrichment limitations can be raised in existing systems, and more compact and economical arrays can be designed. Such reliance on the reduced reactivity of spent fuel for criticality control is referred to as burnup credit. The Burnup Credit Working Group, formed under the auspices of the Nuclear Energy Agency of the Organization for Economic Cooperation and Development, has established a set of well-defined calculational benchmarks designed to study significant aspects of burnup credit computational methods. These benchmarks are intended to provide a means for the intercomparison of computer codes, methods, and data applied in spent fuel analysis. The benchmarks have been divided into multiple phases, each phase focusing on a particular feature of burnup credit analysis. This report summarizes the results and findings of the Phase I-B benchmark, which was proposed to provide a comparison of the ability of different code systems and data libraries to perform depletion analysis for the prediction of spent fuel isotopic concentrations. Results included here represent 21 different sets of calculations submitted by 16 different organizations worldwide and are based on a limited set of nuclides determined to have the most important effect on the neutron multiplication factor of light-water-reactor spent fuel. A comparison of all sets of results demonstrates that most methods agree to within 10% in the ability to estimate the spent fuel concentrations of most actinides. All methods agree within 11% about the average for all fission products studied. Most deviations are less than 10%, and many are less than 5%. The exceptions are Sm 149, Sm 151, and Gd 155.

  19. Bases, Assumptions, and Results of the Flowsheet Calculations for the Decision Phase Salt Disposition Alternatives

    SciTech Connect

    Dimenna, R.A.; Jacobs, R.A.; Taylor, G.A.; Durate, O.E.; Paul, P.K.; Elder, H.H.; Pike, J.A.; Fowler, J.R.; Rutland, P.L.; Gregory, M.V.; Smith III, F.G.; Hang, T.; Subosits, S.G.; Campbell, S.G.

    2001-03-26

    The High Level Waste (HLW) Salt Disposition Systems Engineering Team was formed on March 13, 1998, and chartered to identify options, evaluate alternatives, and recommend a selected alternative(s) for processing HLW salt to a permitted wasteform. This requirement arises because the existing In-Tank Precipitation process at the Savannah River Site, as currently configured, cannot simultaneously meet the HLW production and Authorization Basis safety requirements. This engineering study was performed in four phases. This document provides the technical bases, assumptions, and results of this engineering study.

  20. Loss of lamin B1 results in prolongation of S phase and decondensation of chromosome territories

    PubMed Central

    Camps, Jordi; Wangsa, Darawalee; Falke, Martin; Brown, Markus; Case, Chanelle M.; Erdos, Michael R.; Ried, Thomas

    2014-01-01

    Nuclear lamin B1 (LMNB1) constitutes one of the major structural proteins in the lamina mesh. We silenced the expression of LMNB1 by RNA interference in the colon cancer cell line DLD-1 and showed a dramatic redistribution of H3K27me3 from the periphery to a more homogeneous nuclear dispersion. In addition, we observed telomere attrition and an increased frequency of micronuclei and nuclear blebs. By 3D-FISH analyses, we demonstrated that the volume and surface of chromosome territories were significantly larger in LMNB1-depleted cells, suggesting that LMNB1 is required to maintain chromatin condensation in interphase nuclei. These changes led to a prolonged S phase due to activation of Chk1. Finally, silencing of LMNB1 resulted in extensive changes in alternative splicing of multiple genes and in a higher number of enlarged nuclear speckles. Taken together, our results suggest a mechanistic role of the nuclear lamina in the organization of chromosome territories, maintenance of genome integrity and proper gene splicing.—Camps, J., Wangsa, D., Falke, M., Brown, M., Case, C. M., Erdos, M. R., Ried, T. Loss of lamin B1 results in prolongation of S phase and decondensation of chromosome territories. PMID:24732130

  1. Mucopolysaccharidosis IVA (Morquio A syndrome) and VI (Maroteaux-Lamy syndrome): under-recognized and challenging to diagnose.

    PubMed

    Lachman, Ralph S; Burton, Barbara K; Clarke, Lorne A; Hoffinger, Scott; Ikegawa, Shiro; Jin, Dong-Kyu; Kano, Hiroki; Kim, Ok-Hwa; Lampe, Christina; Mendelsohn, Nancy J; Shediac, Renée; Tanpaiboon, Pranoot; White, Klane K

    2014-03-01

    Mucopolysaccharidosis IVA (MPS IVA, or Morquio A syndrome) and VI (MPS VI, or Maroteaux-Lamy syndrome) are autosomal recessive lysosomal storage disorders. Skeletal abnormalities are common initial presenting symptoms and, when recognized early, may facilitate timely diagnosis and intervention, leading to improved patient outcomes. Patients with slowly progressing disease and nonclassic phenotypes can be particularly challenging to diagnose. The objective was to describe the radiographic features of patients with a delayed diagnosis of MPS IVA or VI. This was a retrospective study. The records of 5 MPS IVA and 3 MPS VI patients with delayed diagnosis were reviewed. Radiographs were evaluated by a radiologist with special expertise in skeletal dysplasias. An important common theme in these cases was the appearance of multiple epiphyseal dysplasia (MED) with epiphyseal changes seemingly confined to the capital (proximal) femoral epiphyses. Very few patients had the skeletal features of classical dysostosis multiplex. Radiologists should appreciate the wide phenotypic variability of MPS IVA and VI. The cases presented here illustrate the importance of considering MPS in the differential diagnosis of certain skeletal dysplasias/disorders, including MED, some forms of spondylo-epiphyseal dysplasia (SED), and bilateral Perthes-like disease. It is important to combine radiographic findings with clinical information to facilitate early testing and accurate diagnosis.

  2. Group IVA phospholipase A2 is associated with the storage of lipids in adipose tissue and liver.

    PubMed

    Ii, Hiromi; Hatakeyama, Shinji; Tsutsumi, Kae; Sato, Takashi; Akiba, Satoshi

    2008-06-01

    Prostaglandin (PG) E(2) is considered to participate in the storage of fat in adipocytes and hepatocytes, but roles of group IVA phospholipase A(2) (PLA(2)), a key PLA(2) isozyme in the arachidonic acid cascade, remain unclear. The present study examined the possible involvement of the enzyme using group IVA PLA(2)-deficient mice (C57BL/6 background, 22 weeks of age) fed a normal diet (5.3% fat). The ratio of epididymal fat pad weight to body weight was significantly reduced in group IVA PLA(2)-deficient mice compared to wild-type mice. Histological analysis revealed that in group IVA PLA(2)-deficient mice, the adipocytes were smaller, and hepatocytes bearing cytoplasmic vacuolation were scarce. Hepatic triglyceride content and the serum levels of PGE(2) in the deficient mice were also lower. However, there was no difference in the serum levels of insulin, glucose, non-esterified free fatty acid, or total cholesterol between the deficient and wild-type mice. Our findings suggest that group IVA PLA(2) is involved in the storage of lipids in the adipose tissue and liver and in determining circulating PGE(2) levels.

  3. Investor Outlook: Significance of the Positive LCA2 Gene Therapy Phase III Results.

    PubMed

    Schimmer, Joshua; Breazzano, Steven

    2015-12-01

    Spark Therapeutics recently reported positive phase III results for SPK-RPE65 targeting the treatment of visual impairment caused by RPE65 gene mutations (often referred to as Leber congenital amaurosis type 2, or LCA2, but may include other retinal disorders), marking an important inflection point for the field of gene therapy. The results highlight the ability to successfully design and execute a randomized trial of a gene therapy and also reinforce the potentially predictive nature of early preclinical and clinical data. The results are expected to pave the way for the first approved gene therapy product in the United States and should sustain investor interest and confidence in gene therapy for many approaches, including retina targeting and beyond.

  4. Switching From Oral Donepezil to Rivastigmine Transdermal Patch in Alzheimer's Disease: 20-Week Extension Phase Results

    PubMed Central

    Dengiz, Alan; Meng, Xiangyi; Olin, Jason T.

    2010-01-01

    Objective: To evaluate the long-term safety, tolerability, and efficacy of 2 strategies for switching from donepezil to rivastigmine transdermal patches in patients with mild to moderate Alzheimer's disease. Method: This was a prospective, 25-week, randomized, open-label, parallel-group study to evaluate an immediate or delayed switch (7-day withdrawal) from donepezil (5 to 10 mg/d) to rivastigmine transdermal patches (4.6 mg/24 h). Participants included male and female patients, aged ≥ 50 years, with a DSM-IV-TR diagnosis of mild to moderate dementia of the Alzheimer's type, defined as a Mini-Mental State Examination score of 10–24, inclusive. Patients were enrolled between February 2007 and February 2008. The study was split into a 5-week core phase and a 20-week extension phase. Safety and efficacy results from the extension phase are presented. Results: Both switching strategies were well tolerated. Rates of discontinuation for any reason were similar between the groups. Discontinuations due to adverse events were also similar, and the incidence of gastrointestinal adverse events was low. Apart from Alzheimer's Disease Cooperative Study–Activities of Daily Living Scale scores, at the end of the study, there was no statistically significant change from baseline in cognitive, behavioral, or global outcomes. Over half of the patients preferred rivastigmine transdermal patches to a tablet. Conclusions: This study suggests that the majority of patients receiving donepezil tablets can be safely switched to rivastigmine transdermal patches without significant deterioration in cognition, behavior, and global functioning. Trial Registration: clinicaltrials.gov Identifier: NCT00305903 PMID:21274364

  5. Jet-Surface Interaction Test: Phased Array Noise Source Localization Results

    NASA Technical Reports Server (NTRS)

    Podboy, Gary G.

    2012-01-01

    An experiment was conducted to investigate the effect that a planar surface located near a jet flow has on the noise radiated to the far-field. Two different configurations were tested: 1) a shielding configuration in which the surface was located between the jet and the far-field microphones, and 2) a reflecting configuration in which the surface was mounted on the opposite side of the jet, and thus the jet noise was free to reflect off the surface toward the microphones. Both conventional far-field microphone and phased array noise source localization measurements were obtained. This paper discusses phased array results, while a companion paper discusses far-field results. The phased array data show that the axial distribution of noise sources in a jet can vary greatly depending on the jet operating condition and suggests that it would first be necessary to know or be able to predict this distribution in order to be able to predict the amount of noise reduction to expect from a given shielding configuration. The data obtained on both subsonic and supersonic jets show that the noise sources associated with a given frequency of noise tend to move downstream, and therefore, would become more difficult to shield, as jet Mach number increases. The noise source localization data obtained on cold, shock-containing jets suggests that the constructive interference of sound waves that produces noise at a given frequency within a broadband shock noise hump comes primarily from a small number of shocks, rather than from all the shocks at the same time. The reflecting configuration data illustrates that the law of reflection must be satisfied in order for jet noise to reflect off of a surface to an observer, and depending on the relative locations of the jet, the surface, and the observer, only some of the jet noise sources may satisfy this requirement.

  6. Recent Results from the Lunar Reconnaissance Orbiter Mission and Plans for the Extended Science Phase

    NASA Technical Reports Server (NTRS)

    Vondrak, Richard; Keller, John W.; Chin, Gordon; Petro, Noah; Garvin, James B.; Rice, James W.

    2012-01-01

    The Lunar Reconnaissance Orbiter spacecraft (LRO), launched on June 18, 2009, began with the goal of seeking safe landing sites for future robotic missions or the return of humans to the Moon as part of NASA's Exploration Systems Mission Directorate (ESMD). In addition, LRO's objectives included the search for surface resources and to investigate the Lunar radiation environment. After spacecraft commissioning, the ESMD phase of the mission began on September 15, 2009 and completed on September 15, 2010 when operational responsibility for LRO was transferred to NASA's Science Mission Directorate (SMD). The SMD mission was scheduled for 2 years and completed in September, 2012. The LRO mission has been extended for two years under SMD. The extended mission focuses on a new set of goals related to understanding the geologic history of the Moon, its current state, and what it can tell us about the evolution Of the Solar System. Here we will review the major results from the LRO mission for both exploration and science and discuss plans and objectives going forward including plans for the extended science phase out to 2014. Results from the LRO mission include but are not limited to the development of comprehensive high resolution maps and digital terrain models of the lunar surface; discoveries on the nature of hydrogen distribution, and by extension water, at the lunar poles; measurement of the day and night time temperature of the lunar surface including temperature down below 30 K in permanently shadowed regions (PSRs); direct measurement of Hg, H2, and CO deposits in the PSRs, evidence for recent tectonic activity on the Moon, and high resolution maps of the illumination conditions as the poles. The objectives for the second and extended science phases of the mission under SMD include: 1) understanding the bombardment history of the Moon, 2) interpreting Lunar geologic processes, 3) mapping the global Lunar regolith, 4) identifying volatiles on the Moon, and 5

  7. Self-contained self-rescuer long term field evaluation: combined eighth and ninth phase results

    SciTech Connect

    2006-10-15

    The National Institute for Occupational Safety and Health (NIOSH) National Personal Protective Technology Laboratory (NPPTL) and the Mine Safety and Health Administration (MSHA) conduct a Long Term Field Evaluation (LTFE) program to evaluate deployed self-contained self rescuers (SCSRs). The objective of the program is to evaluate how well SCSRs endure the underground coal mining environment with regard to both physical damage and aging when they are deployed in accordance with Federal regulations (30 CFR 75.1714). This report presents findings of the combined eighth and ninth phases of the LTFE. For these phases, over four hundred SCSRs were evaluated. The units tested include the CSE SR-100, Draeger Oxy K-Plus, MSA Life-saver 60, and the OCENCO EBA 6.5. The OCENCO 20 was evaluated only in Phase 9. Testing was performed between December 2000 and April 2004. Results of the evaluation indicate that all SCSRs experience some performance degradation due to the mining environment. Observed degradation varies from elevated levels of carbon dioxide, high breathing resistance, and reduced capacity. Mechanical degradation to the SCSR components included breathing hoses, chemical beds, outer cases and seals. The LTFE tests discussed in this report are different from tests performed for SCSR certification to the requirements of 42 Code of Federal Regulations, Part 84 (42 CFR, Part 84). LTFE tests reported here are conducted to an end point, oxygen depletion, to enable comparison of the duration of new and deployed SCSRs. The method for obtaining deployed SCSRs for this evaluation was not a random selection from the deployed population of SCSRs. Although the results of these tests are useful for observing performance of the tested SCSRs, they are not representative of all deployed SCSRs. 9 refs., 10 figs., 9 tabs., 3 apps.

  8. Two-Phase Thermal Transport in Microgap Channels—Theory, Experimental Results, and Predictive Relations

    NASA Astrophysics Data System (ADS)

    Bar-Cohen, Avram; Sheehan, Jessica R.; Rahim, Emil

    2012-01-01

    A comprehensive literature review and analysis of recent microchannel/microgap heat transfer data for two-phase flow of refrigerants and dielectric liquids is presented. The flow regime progression in such a microgap channel is shown to be predicted by the traditional flow regime maps. Moreover, Annular flow is shown to be the dominant regime for this thermal transport configuration and to grow in importance as the channel diameter decreases. The results of heat transfer studies of single miniature channels, as well as the analysis and inverse calculation of IR images of a heated microgap channel wall, are used to identify the existence of a characteristic M-shaped heat transfer coefficient variation with quality (or superficial velocity), with inflection points corresponding to transitions in the two-phase cooling modalities. For the high-quality, Annular flow conditions, the venerable Chen correlation is shown to yield predictive agreement for microgap channels that is comparable to that attained for macrochannels and to provide a mechanistic context for the thermal transport rates attained in microgap channels. Results obtained from infrared imaging, revealing previously undetected, large surface temperature variations in Annular flow, are also reviewed and related to the termination of the favorable thin-film evaporation mode in such channels.

  9. A geometrical shift results in erroneous appearance of low frequency tissue eddy current induced phase maps.

    PubMed

    Mandija, Stefano; van Lier, Astrid L H M W; Katscher, Ulrich; Petrov, Petar I; Neggers, Sebastian F W; Luijten, Peter R; van den Berg, Cornelis A T

    2016-09-01

    Knowledge on low frequency (LF) tissue conductivity is relevant for various biomedical purposes. To obtain this information, LF phase maps arising from time-varying imaging gradients have been demonstrated to create a LF conductivity contrast. Essential in this methodology is the subtraction of phase images acquired with opposite gradient polarities to separate LF and RF phase effects. Here we demonstrate how sensitive these subtractions are with respect to geometrical distortions. The effect of geometrical distortions on LF phase maps is mathematically defined. After quantifying typical geometrical distortions, their effects on LF phase maps are evaluated using conductive phantoms. For validation, electromagnetic simulations of LF phase maps were performed. Even sub-voxel distortions of 10% of the voxel size, measured for a typical LF MR sequence, cause leakage of RF phase into LF phase of several milli-radians, leading to a misleading pattern of LF phase maps. This leakage is mathematically confirmed, while simulations indicate that the expected LF phase should be in order of micro-radians. The conductivity scaling of LF phase maps is attributable to the RF phase leakage, thus dependent on the RF conductivity. In fact, simulations show that the LF phase is not measurable. Magn Reson Med 76:905-912, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  10. T2-weighted four dimensional magnetic resonance imaging with result-driven phase sorting

    SciTech Connect

    Liu, Yilin; Yin, Fang-Fang; Cai, Jing; Czito, Brian G.; Bashir, Mustafa R.

    2015-08-15

    Purpose: T2-weighted MRI provides excellent tumor-to-tissue contrast for target volume delineation in radiation therapy treatment planning. This study aims at developing a novel T2-weighted retrospective four dimensional magnetic resonance imaging (4D-MRI) phase sorting technique for imaging organ/tumor respiratory motion. Methods: A 2D fast T2-weighted half-Fourier acquisition single-shot turbo spin-echo MR sequence was used for image acquisition of 4D-MRI, with a frame rate of 2–3 frames/s. Respiratory motion was measured using an external breathing monitoring device. A phase sorting method was developed to sort the images by their corresponding respiratory phases. Besides, a result-driven strategy was applied to effectively utilize redundant images in the case when multiple images were allocated to a bin. This strategy, selecting the image with minimal amplitude error, will generate the most representative 4D-MRI. Since we are using a different image acquisition mode for 4D imaging (the sequential image acquisition scheme) with the conventionally used cine or helical image acquisition scheme, the 4D dataset sufficient condition was not obviously and directly predictable. An important challenge of the proposed technique was to determine the number of repeated scans (N{sub R}) required to obtain sufficient phase information at each slice position. To tackle this challenge, the authors first conducted computer simulations using real-time position management respiratory signals of the 29 cancer patients under an IRB-approved retrospective study to derive the relationships between N{sub R} and the following factors: number of slices (N{sub S}), number of 4D-MRI respiratory bins (N{sub B}), and starting phase at image acquisition (P{sub 0}). To validate the authors’ technique, 4D-MRI acquisition and reconstruction were simulated on a 4D digital extended cardiac-torso (XCAT) human phantom using simulation derived parameters. Twelve healthy volunteers were involved

  11. Final report of the APRICOT Program and results of Phase 3. [LMFBR

    SciTech Connect

    Not Available

    1982-09-01

    APRICOT (Analysis of PRImary COntainment Transients) was a cooperative activity for comparison and benchmarking of computational methods used to analyze LMFBR (Liquid Metal Fast Breeder Reactor) structural response to pressure loads from HCDA's (Hypothetical Core Disruptive Accidents). The participants were LMFBR project groups from Europe, Japan and the United States. Independent experts reviewed the calculations for the purpose of comparing computational results and methods of solution. Phase 3 involved a series of simple calculations of structural response and fluid-structure interactions under elastic and elastic-plastic conditions. The results were generally in reasonable agreement although there were a few anomalies. The APRICOT program has provided significant code validation data to enhance confidence in numerical simulations of HCDA's. It has also demonstrated the value of this type of benchmark activity.

  12. Gearbox Reliability Collaborative Phase 1 and 2: Testing and Modeling Results; Preprint

    SciTech Connect

    Keller, J.; Guo, Y.; LaCava, W.; Link, H.; McNiff, B.

    2012-05-01

    The Gearbox Reliability Collaborative (GRC) investigates root causes of wind turbine gearbox premature failures and validates design assumptions that affect gearbox reliability using a combined testing and modeling approach. Knowledge gained from the testing and modeling of the GRC gearboxes builds an understanding of how the selected loads and events translate into internal responses of three-point mounted gearboxes. This paper presents some testing and modeling results of the GRC research during Phase 1 and 2. Non-torque loads from the rotor including shaft bending and thrust, traditionally assumed to be uncoupled with gearbox, affect gear and bearing loads and resulting gearbox responses. Bearing clearance increases bearing loads and causes cyclic loading, which could contribute to a reduced bearing life. Including flexibilities of key drivetrain subcomponents is important in order to reproduce the measured gearbox response during the tests using modeling approaches.

  13. The Langley Research Center CSI phase-0 evolutionary model testbed-design and experimental results

    NASA Technical Reports Server (NTRS)

    Belvin, W. K.; Horta, Lucas G.; Elliott, K. B.

    1991-01-01

    A testbed for the development of Controls Structures Interaction (CSI) technology is described. The design philosophy, capabilities, and early experimental results are presented to introduce some of the ongoing CSI research at NASA-Langley. The testbed, referred to as the Phase 0 version of the CSI Evolutionary model (CEM), is the first stage of model complexity designed to show the benefits of CSI technology and to identify weaknesses in current capabilities. Early closed loop test results have shown non-model based controllers can provide an order of magnitude increase in damping in the first few flexible vibration modes. Model based controllers for higher performance will need to be robust to model uncertainty as verified by System ID tests. Data are presented that show finite element model predictions of frequency differ from those obtained from tests. Plans are also presented for evolution of the CEM to study integrated controller and structure design as well as multiple payload dynamics.

  14. Controls-structures interaction guest investigator program: Overview and phase 1 experimental results and future plans

    NASA Technical Reports Server (NTRS)

    Smith-Taylor, Rudeen; Tanner, Sharon E.

    1993-01-01

    The NASA Controls-Structures Interaction (CSI) Guest Investigator program is described in terms of its support of the development of CSI technologies. The program is based on the introduction of CSI researchers from industry and academia to available test facilities for experimental validation of technologies and methods. Phase 1 experimental results are reviewed with attention given to their use of the Mini-MAST test facility and the facility for the Advance Control Evaluation of Structures. Experiments were conducted regarding the following topics: collocated/noncollocated controllers, nonlinear math modeling, controller design, passive/active suspension systems design, and system identification and fault isolation. The results demonstrate that significantly enhanced performance from the control techniques can be achieved by integrating knowledge of the structural dynamics under consideration into the approaches.

  15. [Alemtuzumab for relapsing-remitting multiple sclerosis. Results of two randomized controlled phase III studies].

    PubMed

    Klotz, L; Meuth, S G; Kieseier, B; Wiendl, H

    2013-08-01

    In November 2012 the results of 2 clinical phase III trials were published which addressed the effects of alemtuzumab in patients with relapsing-remitting multiple sclerosis (MS). In the CARE-MS-I study patients with early untreated MS (EDSS ≤ 3.0, disease duration < 5 years) were included, whereas CARE-MS-II investigated the effects of alemtuzumab in patients with persisting disease activity under standard disease-modifying treatment (EDSS ≤ 5.0, disease duration < 10 years). These groups were compared to patients under treatment with frequently applied interferon β 1a (3 times  44 µg subcutaneous). Both studies clearly demonstrated a superiority of alemtuzumab compared to interferon in terms of reduction of relapse rate as well as the number of new or enlarging T2 lesions and gadolinium-enhancing lesions. Moreover, the CARE-MS-II study showed a significant delay in disease progression by alemtuzumab. The portfolio and the frequency of relevant side effects, such as infusion-related reactions, development of secondary autoimmunity or infections were within the expected range. Taken together these studies confirm the high anti-inflammatory efficacy of alemtuzumab and hence provide the first evidence of superiority of a monotherapy in direct comparison to standard disease-modifying treatment in two phase III trials in relapsing-remitting MS. These data in the context of the mode of action of alemtuzumab provide evidence for the relevance of immune cells, especially T cells, in the pathophysiology of MS. Experience with long-term effects of alemtuzumab, e.g. from the phase II extension trial as well as the side effect profile argue in favor of a sustained reprogramming of the immune system as a consequence of immune cell depletion by alemtuzumab.

  16. Simbol-X Hard X-ray Focusing Mirrors: Results Obtained During the Phase A Study

    NASA Astrophysics Data System (ADS)

    Tagliaferri, G.; Basso, S.; Borghi, G.; Burkert, W.; Citterio, O.; Civitani, M.; Conconi, P.; Cotroneo, V.; Freyberg, M.; Garoli, D.; Gorenstein, P.; Hartner, G.; Mattarello, V.; Orlandi, A.; Pareschi, G.; Romaine, S.; Spiga, D.; Valsecchi, G.; Vernani, D.

    2009-05-01

    Simbol-X will push grazing incidence imaging up to 80 keV, providing a strong improvement both in sensitivity and angular resolution compared to all instruments that have operated so far above 10 keV. The superb hard X-ray imaging capability will be guaranteed by a mirror module of 100 electroformed Nickel shells with a multilayer reflecting coating. Here we will describe the technogical development and solutions adopted for the fabrication of the mirror module, that must guarantee an Half Energy Width (HEW) better than 20 arcsec from 0.5 up to 30 keV and a goal of 40 arcsec at 60 keV. During the phase A, terminated at the end of 2008, we have developed three engineering models with two, two and three shells, respectively. The most critical aspects in the development of the Simbol-X mirrors are i) the production of the 100 mandrels with very good surface quality within the timeline of the mission, ii) the replication of shells that must be very thin (a factor of 2 thinner than those of XMM-Newton) and still have very good image quality up to 80 keV, iii) the development of an integration process that allows us to integrate these very thin mirrors maintaining their intrinsic good image quality. The Phase A study has shown that we can fabricate the mandrels with the needed quality and that we have developed a valid integration process. The shells that we have produced so far have a quite good image quality, e.g. HEW <~30 arcsec at 30 keV, and effective area. However, we still need to make some improvements to reach the requirements. We will briefly present these results and discuss the possible improvements that we will investigate during phase B.

  17. Simbol-X Hard X-ray Focusing Mirrors: Results Obtained During the Phase A Study

    SciTech Connect

    Tagliaferri, G.; Basso, S.; Civitani, M.; Conconi, P.; Cotroneo, V.; Pareschi, G.; Spiga, D.; Borghi, G.; Garoli, D.; Mattarello, V.; Orlandi, A.; Valsecchi, G.; Vernani, D.; Burkert, W.; Freyberg, M.; Hartner, G.; Citterio, O.; Gorenstein, P.; Romaine, S.

    2009-05-11

    Simbol-X will push grazing incidence imaging up to 80 keV, providing a strong improvement both in sensitivity and angular resolution compared to all instruments that have operated so far above 10 keV. The superb hard X-ray imaging capability will be guaranteed by a mirror module of 100 electroformed Nickel shells with a multilayer reflecting coating. Here we will describe the technogical development and solutions adopted for the fabrication of the mirror module, that must guarantee an Half Energy Width (HEW) better than 20 arcsec from 0.5 up to 30 keV and a goal of 40 arcsec at 60 keV. During the phase A, terminated at the end of 2008, we have developed three engineering models with two, two and three shells, respectively. The most critical aspects in the development of the Simbol-X mirrors are i) the production of the 100 mandrels with very good surface quality within the timeline of the mission, ii) the replication of shells that must be very thin (a factor of 2 thinner than those of XMM-Newton) and still have very good image quality up to 80 keV, iii) the development of an integration process that allows us to integrate these very thin mirrors maintaining their intrinsic good image quality. The Phase A study has shown that we can fabricate the mandrels with the needed quality and that we have developed a valid integration process. The shells that we have produced so far have a quite good image quality, e.g. HEW < or approx. 30 arcsec at 30 keV, and effective area. However, we still need to make some improvements to reach the requirements. We will briefly present these results and discuss the possible improvements that we will investigate during phase B.

  18. The measurement of operator workload in the Mark IVA DSCC monitor and control subsystem

    NASA Technical Reports Server (NTRS)

    Lemay, M.; Chafin, R. L.; Hird, E. E.

    1983-01-01

    An operator workload measurement methodology is presented which will be used in support of the Mark IVA operational test and evaluation plan. Three operator workload measures are suggested: operator ratings, primary task work measures, and information processing time measures. A method of validating the workload measures using secondary task work measures is presented. It is expected that operations testing using these measures will assist in establishing the time required to perform essential operational activities and will indicate high risk operations areas due to potential operator overload.

  19. Retrospective Analysis of the Survival Benefit of Induction Chemotherapy in Stage IVa-b Nasopharyngeal Carcinoma.

    PubMed

    Lan, Xiao-Wen; Zou, Xue-Bin; Xiao, Yao; Tang, Jie; OuYang, Pu-Yun; Su, Zhen; Xie, Fang-Yun

    2016-01-01

    The value of adding induction chemotherapy to chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains controversial, yet high-risk patients with LA-NPC have poor outcomes after chemoradiotherapy. We aimed to assess the survival benefits of induction chemotherapy in stage IVa-b NPC. A total of 602 patients with stage IVa-b NPC treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy with or without induction chemotherapy were retrospectively analyzed. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, log-rank test and Cox regression analysis. In univariate analysis, 5-year OS was 83.2% for induction chemotherapy plus concurrent chemotherapy and 74.8% for concurrent chemotherapy alone, corresponding to an absolute risk reduction of 8.4% (P = 0.022). Compared to concurrent chemotherapy alone, addition of induction chemotherapy improved 5-year DMFS (83.2% vs. 74.4%, P = 0.018) but not 5-year LRFS (83.7% vs. 83.0%, P = 0.848) or PFS (71.9% vs. 66.0%, P = 0.12). Age, T category, N category, chemotherapy strategy and clinical stage were associated with 5-year OS (P = 0.017, P = 0.031, P = 0.007, P = 0.022, P = 0.001, respectively). In multivariate analysis, induction chemotherapy plus concurrent chemotherapy was an independent favorable prognostic factor for OS (HR, 0.62; 95% CI, 0.43-0.90, P = 0.012) and DMFS (HR, 0.57; 95% CI, 0.38-0.83, P = 0.004). In subgroup analysis, induction chemotherapy significantly improved 5-year DMFS in stage IVa (86.8% vs. 77.3%, P = 0.008), but provided no significant benefit in stage IVb. In patients with stage IVa-b NPC treated with IMRT, addition of induction chemotherapy to concurrent chemotherapy significantly improved 5-year OS and 5-year DMFS. This study provides a basis for selection of high risk patients in future clinical therapeutic

  20. Ecdysteroid profiles of two Ajuga species, A. iva and A. remota.

    PubMed

    Bakrim, Ahmed; Ngunjiri, Johnpeter; Crouzet, Sophie; Guibout, Louis; Balducci, Christine; Girault, Jean-Pierre; Lafont, René

    2014-08-01

    Phytoecdysteroids are plant analogues of insect moulting hormones and are used by plants to repel or disturb phytophagous insects. They are also active on mammals and present in many plants used in traditional medicine. The Ajuga genus contains several such species, which occur in various pharmacopoeias. We report the isolation and identification of major and minor ecdysteroids present in two Ajuga species, A. iva and A. remota, both of which are used as medicinal plants in Africa. Three minor ecdysteroids (abutasterone, ponasterone A and sidisterone) have been found for the first time in the Ajuga genus.

  1. Isolation of four ecdysones from Ajuga iva roots and a rapid semiquantitative method for ecdysone determination.

    PubMed

    Sabri, N N; Asaad, A; Khafagy, S M

    1981-07-01

    The ethereal extract of AJUGA IVA (L.) S CHREB. roots, yielded 4 ecdysones. Three were proved to be cyasterone, makisterone A and ecdysterone, by using UV, IR, MS spectral methods and comparison with standard samples. Spectral data indicate that the fourth ecdysone is similar to cyasterone but having an additional hydroxy group in the side-chain. The chromatographic pattern of ecdysone content in roots, stems and leaves is presented as well as a rapid and simple Semiquantitative method for their estimation. The roots had the highest total content (0.381%).

  2. The measurement of operator workload in the Mark IVA DSCC monitor and control subsystem

    NASA Technical Reports Server (NTRS)

    Lemay, M.; Chafin, R. L.; Hird, E. E.

    1983-01-01

    An operator workload measurement methodology is presented which will be used in support of the Mark IVA operational test and evaluation plan. Three operator workload measures are suggested: operator ratings, primary task work measures, and information processing time measures. A method of validating the workload measures using secondary task work measures is presented. It is expected that operations testing using these measures will assist in establishing the time required to perform essential operational activities and will indicate high risk operations areas due to potential operator overload.

  3. Results and Lessons Learned from Phase 1 of the Air Quality Model Evaluation International Initiative (AQMEII)

    EPA Science Inventory

    A summary of the key findings from the model evaluation studies performed for the Phase 1 annual 2006 North American and European simulations, as well as reflections on experiences gained during Phase 1 that will be important for guiding the implementation of Phase 2 of the Air Q...

  4. Results and Lessons Learned from Phase 1 of the Air Quality Model Evaluation International Initiative (AQMEII)

    EPA Science Inventory

    A summary of the key findings from the model evaluation studies performed for the Phase 1 annual 2006 North American and European simulations, as well as reflections on experiences gained during Phase 1 that will be important for guiding the implementation of Phase 2 of the Air Q...

  5. T2-weighted four dimensional magnetic resonance imaging with result-driven phase sorting.

    PubMed

    Liu, Yilin; Yin, Fang-Fang; Czito, Brian G; Bashir, Mustafa R; Cai, Jing

    2015-08-01

    T2-weighted MRI provides excellent tumor-to-tissue contrast for target volume delineation in radiation therapy treatment planning. This study aims at developing a novel T2-weighted retrospective four dimensional magnetic resonance imaging (4D-MRI) phase sorting technique for imaging organ/tumor respiratory motion. A 2D fast T2-weighted half-Fourier acquisition single-shot turbo spin-echo MR sequence was used for image acquisition of 4D-MRI, with a frame rate of 2-3 frames/s. Respiratory motion was measured using an external breathing monitoring device. A phase sorting method was developed to sort the images by their corresponding respiratory phases. Besides, a result-driven strategy was applied to effectively utilize redundant images in the case when multiple images were allocated to a bin. This strategy, selecting the image with minimal amplitude error, will generate the most representative 4D-MRI. Since we are using a different image acquisition mode for 4D imaging (the sequential image acquisition scheme) with the conventionally used cine or helical image acquisition scheme, the 4D dataset sufficient condition was not obviously and directly predictable. An important challenge of the proposed technique was to determine the number of repeated scans (NR) required to obtain sufficient phase information at each slice position. To tackle this challenge, the authors first conducted computer simulations using real-time position management respiratory signals of the 29 cancer patients under an IRB-approved retrospective study to derive the relationships between NR and the following factors: number of slices (NS), number of 4D-MRI respiratory bins (NB), and starting phase at image acquisition (P0). To validate the authors' technique, 4D-MRI acquisition and reconstruction were simulated on a 4D digital extended cardiac-torso (XCAT) human phantom using simulation derived parameters. Twelve healthy volunteers were involved in an IRB-approved study to investigate the

  6. Jet-Surface Interaction Test: Phased Array Noise Source Localization Results

    NASA Technical Reports Server (NTRS)

    Podboy, Gary G.

    2013-01-01

    An experiment was conducted to investigate the effect that a planar surface located near a jet flow has on the noise radiated to the far-field. Two different configurations were tested: 1) a shielding configuration in which the surface was located between the jet and the far-field microphones, and 2) a reflecting configuration in which the surface was mounted on the opposite side of the jet, and thus the jet noise was free to reflect off the surface toward the microphones. Both conventional far-field microphone and phased array noise source localization measurements were obtained. This paper discusses phased array results, while a companion paper (Brown, C.A., "Jet-Surface Interaction Test: Far-Field Noise Results," ASME paper GT2012-69639, June 2012.) discusses far-field results. The phased array data show that the axial distribution of noise sources in a jet can vary greatly depending on the jet operating condition and suggests that it would first be necessary to know or be able to predict this distribution in order to be able to predict the amount of noise reduction to expect from a given shielding configuration. The data obtained on both subsonic and supersonic jets show that the noise sources associated with a given frequency of noise tend to move downstream, and therefore, would become more difficult to shield, as jet Mach number increases. The noise source localization data obtained on cold, shock-containing jets suggests that the constructive interference of sound waves that produces noise at a given frequency within a broadband shock noise hump comes primarily from a small number of shocks, rather than from all the shocks at the same time. The reflecting configuration data illustrates that the law of reflection must be satisfied in order for jet noise to reflect off of a surface to an observer, and depending on the relative locations of the jet, the surface, and the observer, only some of the jet noise sources may satisfy this requirement.

  7. Phases of QCD from Small to Large Nf:. (Some) Lattice Results

    NASA Astrophysics Data System (ADS)

    Deuzeman, A.; Pallante, E.; Lombardo, M. P.

    2011-01-01

    We analyze the phases of strong interactions in the space of the flavor number Nf, bare coupling gL, and temperature T by lattice MonteCarlo simulations for two and three unrooted staggered flavors, corresponding to eight and twelve continuum flavors, respectively. We observe a Coulomb-like phase at intermediate lattice couplings which we interpret as the avatar of a continuum conformal theory for Nf = 12. We comment on the possible occurrence of an UVFP associated with the bulk phase transition between the strong coupling lattice phase and the Coulomb-like phase.

  8. Disorder-induced phase transition in an opinion dynamics model: Results in two and three dimensions

    NASA Astrophysics Data System (ADS)

    Mukherjee, Sudip; Chatterjee, Arnab

    2016-12-01

    We study a model of continuous opinion dynamics with both positive and negative mutual interactions. The model shows a continuous phase transition between a phase with consensus (order) and a phase having no consensus (disorder). The mean field version of the model was already studied. Using extensive numerical simulations, we study the same model in two and three dimensions. The critical points of the phase transitions for various cases and the associated critical exponents have been estimated. The universality class of the phase transitions in the model is found to be same as Ising model in the respective dimensions.

  9. Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy in locally advanced squamous cell carcinoma of the uterine cervix: Results of a phase II study

    SciTech Connect

    Vrdoljak, Eduard . E-mail: eduard.vrdoljak@st.hinet.hr; Prskalo, Tomislav; Omrcen, Tomislav; Situm, Kristina; Boraska, Tihana; Frleta Ilic, Nives; Jankovic, Stjepan; Hamm, Wolfgang

    2005-03-01

    Purpose: To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose-rate brachytherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell cervical carcinoma (LASCC). Methods and materials: Forty-four patients with biopsy-proven LASCC were enrolled. FIGO Stages IB2 bulky to IVA were entered into this study. Patients were assigned to receive external radiotherapy (50 Gy in 25 fractions); then ifosfamide 2 g/m{sup 2} plus cisplatin 75 mg/m{sup 2} was applied during two low-dose-rate brachytherapy applications, and 4 cycles of consolidation chemotherapy with the same drug combination were given after completion of radiotherapy. The planned dose to point A was 85 Gy. Results: All patients received both courses of concomitant chemobrachytherapy and at least 1 cycle of consolidation chemotherapy. The average duration of radiation was 45.1 days. The clinical complete response rate was 100%. Grade 3 and 4 leukopenia occurred in 25% and 11% of the cycles, respectively. After a median follow-up of 34 months (range, 20-54 months), the recurrence-free and the overall survival rates were 84% and 91%, respectively. Major delayed local complications occurred in 7 cases (16%). Conclusions: These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin is a feasible combination for patients with LASCC of the cervix uteri. A randomized trial is planned.

  10. Convergent validity of the Integrated Visual and Auditory Continuous Performance Test (IVA+Plus): associations with working memory, processing speed, and behavioral ratings.

    PubMed

    Arble, Eamonn; Kuentzel, Jeffrey; Barnett, Douglas

    2014-05-01

    Though the Integrated Visual and Auditory Continuous Performance Test (IVA + Plus) is commonly used by researchers and clinicians, few investigations have assessed its convergent and discriminant validity, especially with regard to its use with children. The present study details correlates of the IVA + Plus using measures of cognitive ability and ratings of child behavior (parent and teacher), drawing upon a sample of 90 psychoeducational evaluations. Scores from the IVA + Plus correlated significantly with the Working Memory and Processing Speed Indexes from the Fourth Edition of the Wechsler Intelligence Scales for Children (WISC-IV), though fewer and weaker significant correlations were seen with behavior ratings scales, and significant associations also occurred with WISC-IV Verbal Comprehension and Perceptual Reasoning. The overall pattern of relations is supportive of the validity of the IVA + Plus; however, general cognitive ability was associated with better performance on most of the primary scores of the IVA + Plus, suggesting that interpretation should take intelligence into account.

  11. NASA Broad Specification Fuels Combustion Technology program - Pratt and Whitney Aircraft Phase I results and status

    NASA Technical Reports Server (NTRS)

    Lohmann, R. P.; Fear, J. S.

    1982-01-01

    In connection with increases in the cost of fuels and the reduced availability of high quality petroleum crude, a modification of fuel specifications has been considered to allow acceptance of poorer quality fuels. To obtain the information upon which a selection of appropriate fuels for aircraft can be based, the Broad Specification Fuels Combustion Technology program was formulated by NASA. A description is presented of program-related investigations conducted by an American aerospace company. The specific objective of Phase I of this program has been to evaluate the impact of the use of broadened properties fuels on combustor design through comprehensive combustor rig testing. Attention is given to combustor concepts, experimental evaluation, results obtained with single stage combustors, the stage combustor concept, and the capability of a variable geometry combustor.

  12. Bubble Generation in a Flowing Liquid Medium and Resulting Two-Phase Flow in Microgravity

    NASA Technical Reports Server (NTRS)

    Kamotani, Yasuhiro

    1996-01-01

    An experimental and theoretical research program is described herein to study bubble generation in a liquid flow in a pipe under reduced gravity conditions. The objective of the work is to study the bubble size and frequency of the generation and the resulting two-phase flow but it also concerns the fluid mechanical aspects of boiling in forced flow in microgravity. By injecting a gas into a liquid flow in a pipe through a small hole in the pipe wall we will investigate how the bubble expands and detaches from the wall, without involving the complexities of boiling. The experiments will be conducted both under isothermal conditions and with heat transfer from the wall. In the experiments with heat transfer the effect of thermocapillarity on the bubble formation and detachment will be the main subject.

  13. RESULTS FROM BETATRON PHASE MEASUREMENTS IN RHIC DURING THE SEXTANT TEST.

    SciTech Connect

    TRBOJEVIC, D.

    1998-06-26

    The Sextant Test of the Relativistic Heavy Ion Collider (RHIC) was an important step towards its completion. One sixth of the two RHIC accelerators was fully commissioned. Gold ion beam was injected and transported through one sextant of one of the two rings. The betatron phase advance per cell was measured by recording differences in the horizontal and vertical positions of the beam at the end of the sextant due to a sequence of correction dipole kicks along the beam line. Measurement results show excellent agreement with predicted values, confirming that production measurements of the integral functions of the quadrupoles were very accurate, and that the polarity of all elements (correction dipoles, quadrupoles, dipoles etc.) was correct.

  14. Results from betatron phase measurements in RHIC during the sextant test

    SciTech Connect

    Trbojevic, D.; Connolly, R.; Fischer, W.

    1998-08-01

    The Sextant Test of the Relativistic Heavy Ion Collider (RHIC) was an important step towards its completion. One sixth of the two RHIC accelerators was fully commissioned. gold ion beam was injected and transported through one sextant of one of the two rings. The betatron phase advance per cell was measured by recording differences in the horizontal and vertical positions of the beam at the end of the sextant due to a sequence of correction dipole kicks along the beam line. Measurement results show excellent agreement with predicted values, confirming that production measurements of the integral functions of the quadrupoles were very accurate, and that the polarity of all elements (correction dipoles, quadrupoles, dipoles etc.) was correct.

  15. NASA Broad Specification Fuels Combustion Technology program - Pratt and Whitney Aircraft Phase I results and status

    NASA Technical Reports Server (NTRS)

    Lohmann, R. P.; Fear, J. S.

    1982-01-01

    In connection with increases in the cost of fuels and the reduced availability of high quality petroleum crude, a modification of fuel specifications has been considered to allow acceptance of poorer quality fuels. To obtain the information upon which a selection of appropriate fuels for aircraft can be based, the Broad Specification Fuels Combustion Technology program was formulated by NASA. A description is presented of program-related investigations conducted by an American aerospace company. The specific objective of Phase I of this program has been to evaluate the impact of the use of broadened properties fuels on combustor design through comprehensive combustor rig testing. Attention is given to combustor concepts, experimental evaluation, results obtained with single stage combustors, the stage combustor concept, and the capability of a variable geometry combustor.

  16. Clinical results of real-time ultrasonic scanning of the heart using a phased array system.

    PubMed

    Kisslo, J A; vonRamm, O T; Thurstone, F L

    1977-01-01

    This report describes the operating characteristics and initial clinical results of a new echocardiographic system that produces real-time, high resolution, cross-sectional images of the heart. This system relies upon phased-array principles to rapidly steer and focus the ultrasound beam through the cardiac structures under investigation. A hand-held, linear array of 24 transducers is manipulated on the patient's chest to direct the interrogating plane at various cardiac structures. Images of high line density are presented in selectable sector arcs to a maximum of 90 degrees. This imaging system has been used clinically in over 2,000 patients in the past two and one-half years. Its use in the detection of altered states of ventricular and valvular pathology has been described.

  17. Density-functional correction of random-phase-approximation correlation with results for jellium surface energies

    NASA Astrophysics Data System (ADS)

    Kurth, Stefan; Perdew, John P.

    1999-04-01

    Since long-range electron-electron correlation is treated properly in the random phase approximation (RPA), we define short-range correlation as the correction to the RPA. The effects of short-range correlation are investigated here in the local spin density (LSD) approximation and the generalized gradient approximation (GGA). Results are presented for atoms, molecules, and jellium surfaces. It is found that (1) short-range correlation energies are less sensitive to the inclusion of density gradients than are full correlation energies, and (2) short-range correlation makes a surprisingly small contribution to surface and molecular atomization energies. In order to improve the accuracy of electronic-structure calculations, we therefore combine a GGA treatment of short-range correlation with a full RPA treatment of the exchange-correlation energy. This approach leads to jellium surface energies close to those of the LSD approximation for exchange and correlation together (but not for each separately).

  18. Artemis common lunar lander. Phase 2: Study results for external review

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The purpose of the Artemis Program is to gather vital reconnaissance data by conducting robotic exploration missions to the lunar surface both prior to and concurrent with human exploration missions. The Artemis Program includes rapid, near-term development of a variety of small experimental and operational payloads, provides a low-cost capability to deliver these payloads to any location on the lunar surface, and supports the analysis of the data returned. The Artemis Program will improve the understanding of lunar geosciences, demonstrate the Moon's unique capability as an astronomical platform to study the universe, and to conduct scientific and technology development experiments, and will prepare for, enhance, and complement human mission The Artemis Common Lunar Lander Phase 2 Study results for external review are included.

  19. Chikusetsusaponin IVa methyl ester induces G1 cell cycle arrest, triggers apoptosis and inhibits migration and invasion in ovarian cancer cells.

    PubMed

    Chen, Xin; Wu, Qiu-Shuang; Meng, Fan-Cheng; Tang, Zheng-Hai; Chen, Xiuping; Lin, Li-Gen; Chen, Ping; Qiang, Wen-An; Wang, Yi-Tao; Zhang, Qing-Wen; Lu, Jin-Jian

    2016-12-01

    Panacis Japonici Rhizoma (PJR) is one of the most famous Chinese medical herbs that is known for exhibiting potential anti-cancer effects. This study aims to isolate and investigate the anti-cancer potential of saponins from PJR in ovarian cancer cells. The compounds were separated by comprehensive chromatographic methods. By comparison of the 1H- and 13C NMR data, as well as the HR-ESI-MS data, with the corresponding references, the structures of compounds were determined. MTT assay was performed to evaluate cell viability, along with flow cytometry for cell cycle analysis. JC-1 staining, Annexin V-PI double staining as well as Hoechst 33; 342 staining were used for detecting cell apoptosis. Western blot analysis was conducted to determine the relative protein level. Transwell assays were performed to investigate the effect of the saponin on cell migration and invasion and zymography experiments were used to detect the enzymatic activities. Eleven saponins were isolated from PJR and their anti-proliferative effects were evaluated in human ovarian cancer cells. Chikusetsusaponin IVa methyl ester (1) exhibited the highest anti-proliferative potential among these isolates with the IC50 values at less than 10 µM in both ovarian cancer A2780 and HEY cell lines. Compound 1 induced G1 cell cycle arrest accompanied with an S phase decrease, and down-regulated the expression of cyclin D1, CDK2, and CDK6. Further study showed that compound 1 effectively decreased the cell mitochondrial membrane potential, increased the annexin V positive cells and nuclear chromatin condensation, as well as enhanced the expression of cleaved PARP, Bax and cleaved-caspase 3 while decreasing that of Bcl-2. Moreover, compound 1 suppressed the migration and invasion of HEY and A2780 cells, down-regulated the expression of Cdc42, Rac, RohA, MMP2 and MMP9, and decreased the enzymatic activities of MMP2 and MMP9. These results provide a comprehensive evaluation of compound 1 as a potential agent

  20. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial

    PubMed Central

    Motzer, Robert J.; Rini, Brian I.; McDermott, David F.; Redman, Bruce G.; Kuzel, Timothy M.; Harrison, Michael R.; Vaishampayan, Ulka N.; Drabkin, Harry A.; George, Saby; Logan, Theodore F.; Margolin, Kim A.; Plimack, Elizabeth R.; Lambert, Alexandre M.; Waxman, Ian M.; Hammers, Hans J.

    2015-01-01

    Purpose Nivolumab is a fully human immunoglobulin G4 programmed death–1 immune checkpoint inhibitor antibody that restores T-cell immune activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned (blinded ratio of 1:1:1) to nivolumab 0.3, 2, or 10 mg/kg intravenously once every 3 weeks. The primary objective was to evaluate the dose-response relationship as measured by progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), and safety. Results A total of 168 patients were randomly assigned to the nivolumab 0.3- (n = 60), 2- (n = 54), and 10-mg/kg (n = 54) cohorts. One hundred eighteen patients (70%) had received more than one prior systemic regimen. Median PFS was 2.7, 4.0, and 4.2 months, respectively (P = .9). Respective ORRs were 20%, 22%, and 20%. Median OS was 18.2 months (80% CI, 16.2 to 24.0 months), 25.5 months (80% CI, 19.8 to 28.8 months), and 24.7 months (80% CI, 15.3 to 26.0 months), respectively. The most common treatment-related adverse event (AE) was fatigue (24%, 22%, and 35%, respectively). Nineteen patients (11%) experienced grade 3 to 4 treatment-related AEs. Conclusion Nivolumab demonstrated antitumor activity with a manageable safety profile across the three doses studied in mRCC. No dose-response relationship was detected as measured by PFS. These efficacy and safety results in mRCC support study in the phase III setting. PMID:25452452

  1. Late-phase melt progression experiment: MP-2. Results and analysis

    SciTech Connect

    Gasser, R.D.; Gauntt, R.O.; Bourcier, S.C.

    1997-05-01

    In-pile experiments addressing late-phase processes in Light Water Reactors (LWRs) were performed in the Annular Core Research Reactor (ACRR) at Sandia National Laboratories. Melt Progression (MP) experiments were designed to provide information to develop and verify computer models for analysis of LWR core damage in severe accidents. Experiments examine the formation and motion of ceramic molten pools in disrupted reactor core regions. The MP-2 experiment assembly consisted of: (1) a rubble bed of enriched UO{sub 2} and ZrO{sub 2} simulating severely disrupted reactor core regions, (2) a ceramic/metallic crust representing blockage formed by early phase melting, relocation, and refreezing of core components, and (3) an intact rod stub region that remained in place below the blockage region. The test assembly was fission heated in the central cavity of the ACRR at an average rate of about 0.2 KA, reaching a peak molten pool temperature around 3400 K. Melting of the debris bed ceramic components was initiated near the center of the bed. The molten material relocated downward, refreezing to form a ceramic crust near the bottom of the rubble bed. As power levels were increased, the crust gradually remelted and reformed at progressively lower positions in the bed until late in the experiment when it penetrated into and attacked the ceramic/metallic blockage. The metallic components of the blockage region melted and relocated to the bottom of the intact rod stub region before the ceramic melt penetrated the blockage region from above. The ceramic pool penetrated halfway into the blockage region by the end of the experiment. Measurements of thermal response and material relocation are compared to the results of the computer simulations. Postexperiment examination of the assembly with the associated material interactions and metallurgy are also discussed in detail with the analyses and interpretation of results. 16 refs., 206 figs., 24 tabs.

  2. Phase 1 results of the NFRC U-Value Procedure Validation Project

    SciTech Connect

    Arasteh, D.; Beck, F.A.; Stone, N.; duPont, W.; Mathis, C.; Koenig, M.

    1993-08-01

    The NFRC U-Value Procedure Validation Project was undertaken by a collaborative group of industry, public utility, trade associations, and government researchers in order to validate the testing and calculational methods of the NFRC 100-91: Procedure for Determining Fenestration Product Thermal Properties (Currently Limited to U-Values). This paper summarizes the validation project s goals and test methodology, the results of the data analysis, and the recommendations following completion of Phase I of the project. Simulations performed according to NFRC 100-91 are shown to agree with each other, to within the NFRC tolerance, in 100% of the cases. Window test results with perpendicular wind performed according to NFRC 100-91 are shown to agree with each other, to within the NFRC tolerance, in 84% of the cases. Simulations and perpendicular wind window test results are shown to agree with each other, to within the NFRC tolerance, in 80% of the cases. Testing of skylights was shown to be problematic under the procedure as written at the time. Agreement between tests and simulations will improve as a result of a strong NFRC education and accreditation program.

  3. Analytical Round Robin for Elastic-Plastic Analysis of Surface Cracked Plates, Phase II Results

    NASA Technical Reports Server (NTRS)

    Allen, P. A.; Wells, D. N.

    2017-01-01

    The second phase of an analytical round robin for the elastic-plastic analysis of surface cracks in flat plates was conducted under the auspices of ASTM Interlaboratory Study 732. The interlaboratory study (ILS) had 10 participants with a broad range of expertise and experience, and experimental results from a surface crack tension test in 4142 steel plate loaded well into the elastic-plastic regime provided the basis for the study. The participants were asked to evaluate a surface crack tension test according to the version of the surface crack initiation toughness testing standard published at the time of the ILS, E2899-13. Data were provided to each participant that represent the fundamental information that would be provided by a mechanical test laboratory prior to evaluating the test result. Overall, the participant’s test analysis results were in good agreement and constructive feedback was received that has resulted in an improved published version of the standard E2899-15.

  4. The group I pilin glycan affects type IVa pilus hydrophobicity and twitching motility in Pseudomonas aeruginosa 1244

    PubMed Central

    Allison, Tara M.; Conrad, Sean

    2015-01-01

    The group I pilin category is the most common type of type IVa pilus produced by Pseudomonas aeruginosa. The lateral surfaces of these pili are characterized by the presence of closely spaced, covalently attached O-antigen repeating units. The current work was conducted to investigate the pilin glycan's effect on pilus solubility and function. Culture supernatant fluids containing fully, partially and non-glycosylated P. aeruginosa group I pili were tested for solubility in the presence of ammonium sulfate. These results showed that while pili expressing three or four sugars were highly soluble under all conditions, those with fewer than three were insoluble under the lowest salt concentrations tested. A representative of the P. aeruginosa group II pili also showed low solubility when assayed under these same conditions. Reduced solubility suggested an increased pilus surface hydrophobicity, which was supported by protein modelling. While having no effect on the WT strain, an ionic strength found at many host infection sites inhibited surface and subsurface twitching motility of strain 1244G7, an isogenic mutant unable to glycosylate pilin. This effect was reversed by mutant complementation. Twitching motility of P. aeruginosa strain PA103, which produces group II pili, was also inhibited by ionic strengths which influenced the mutant 1244 strain. We suggest that the group I pilin glycan may, therefore, be beneficial to this organism specifically for optimal pilus functioning at the many host disease sites with ionic strengths comparable to those tested here. PMID:26297472

  5. Hanna, Wyoming underground coal gasification data base. Volume 6. Hanna IVA and IVB field test research report

    SciTech Connect

    Bartke, T.C.; Fischer, D.D.; King, S.B.; Boyd, R.M.; Humphrey, A.E.

    1985-08-01

    This report is part of a seven-volume series on the Hanna, Wyoming, underground coal gasification field tests. Volume 1 is a summary of the project and each of Volumes 2 through 6 describes a particular test. Volume 7 is a compilation of all the data for the tests in Volumes 2 through 6. The reports in this series include: The Hanna IV test was designed as the first underground coal gasification test using commercial well spacings of 100 and 150 feet between well pairs in a linear 3-well pattern. The test was initiated in late 1977 and completed in late 1979. This long duration was due to unfavorable geologic conditions (faulting) which could not be successfully overcome resulting in the test being split into Hanna IVA and Hanna IVB with about one year between the conduct of each. This report covers: (1) specific site selection and characteristics; (2) test objectives; (3) facility description; (4) pre-operation tests; (5) test operations summary; and (6) post-test activity. 5 refs., 19 figs., 13 tabs.

  6. Theoretical Studies Of Group IVA And Group IVB Chemistry

    DTIC Science & Technology

    2014-08-20

    reaction paths. The R(-7) dispersion terms was also derived and coded. While most workers ignore the odd power dispersion terms, these terms can be...second order perturbation theory (MP2) to help explain the experimental results of the Fayer group on phenol migration dynamics. An exhaustive...2013) 3. L. Kocia, S. Young, Y. Kholod, M. Gordon, M. Fayer, and A. Rappe, “Theoretical Examination of Picosecond Phenol Migration Dynamics in

  7. Results for Phase I of the IAEA Coordinated Research Program on HTGR Uncertainties

    SciTech Connect

    Strydom, Gerhard; Bostelmann, Friederike; Yoon, Su Jong

    2015-01-01

    The quantification of uncertainties in design and safety analysis of reactors is today not only broadly accepted, but in many cases became the preferred way to replace traditional conservative analysis for safety and licensing analysis. The use of a more fundamental methodology is also consistent with the reliable high fidelity physics models and robust, efficient, and accurate codes available today. To facilitate uncertainty analysis applications a comprehensive approach and methodology must be developed and applied. High Temperature Gas-cooled Reactors (HTGR) has its own peculiarities, coated particle design, large graphite quantities, different materials and high temperatures that also require other simulation requirements. The IAEA has therefore launched a Coordinated Research Project (CRP) on the HTGR Uncertainty Analysis in Modeling (UAM) in 2013 to study uncertainty propagation specifically in the HTGR analysis chain. Two benchmark problems are defined, with the prismatic design represented by the General Atomics (GA) MHTGR-350 and a 250 MW modular pebble bed design similar to the HTR-PM (INET, China). This report summarizes the contributions of the HTGR Methods Simulation group at Idaho National Laboratory (INL) up to this point of the CRP. The activities at INL have been focused so far on creating the problem specifications for the prismatic design, as well as providing reference solutions for the exercises defined for Phase I. An overview is provided of the HTGR UAM objectives and scope, and the detailed specifications for Exercises I-1, I-2, I-3 and I-4 are also included here for completeness. The main focus of the report is the compilation and discussion of reference results for Phase I (i.e. for input parameters at their nominal or best-estimate values), which is defined as the first step of the uncertainty quantification process. These reference results can be used by other CRP participants for comparison with other codes or their own reference

  8. The PICASSO project: MT Investigation in Southern Spain and Morocco - Results of phase I and outlook on phase II

    NASA Astrophysics Data System (ADS)

    Kiyan, D.; Schmoldt, J.; Jones, A. G.; Hogg, C.; Rosell, O.

    2009-12-01

    PICASSO (Project to Investigate Convective Alboran Sea System Overturn) is an international, multi-disciplinary project that aims to improve knowledge of the internal structure and plate-tectonic processes in the highly complex three-dimensional region formed by the collision of the African and European plate under the effect of the Mediterranean plate motion. The first phase of the DIAS magnetotelluric (MT) component of the PICASSO project was carried out in Southern Spain from Sept.-Nov., 2007 focused on the investigation of the internal structure of the Betic Mountain Chain and the Iberian Basement. Two different types of magnetotelluric (MT) equipment - broadband (BBMT) and long period (LMT) MT - were used along a profile from the outskirts of Madrid to the Mediterranean Sea through the Betic Mountain Chain. The modified acquisition design of one of the equipment types (the LVIV LEMI long period system), with separate recording of each telluric channel, allowed for advanced investigation of the acquired dataset. The data were processed using four different robust algorithms, and the different responses have been compared. A distinct separation can be made between the Betics region of Alpine orogeny in the south and the Variscan Iberian Massif beneath the north of the profile in terms of their inherent electric conductivity characteristics. Models derived by two-dimensional inversions of regional responses, after removing distortion effects, from this first phase show a remarkably complex subsurface structure beneath the region of the External Betic Chain. Strike direction varies along the profile and with depth due to the intricate morphology, and its choice has significant impact on the responses to be modelled and thereby provides a challenging framework for MT data interpretation. The second phase of PICASSO aims to shed light onto the origin of the Atlas Mountain Chain and test hypotheses for its missing mantle root derived from heat flow, gravity, geoid

  9. Final Analysis and Results of the Phase II SIMPLE Dark Matter Search

    NASA Astrophysics Data System (ADS)

    Felizardo, M.; Girard, T. A.; Morlat, T.; Fernandes, A. C.; Ramos, A. R.; Marques, J. G.; Kling, A.; Puibasset, J.; Auguste, M.; Boyer, D.; Cavaillou, A.; Poupeney, J.; Sudre, C.; Miley, H. S.; Payne, R. F.; Carvalho, F. P.; Prudêncio, M. I.; Gouveia, A.; Marques, R.

    2012-05-01

    We report the final results of the Phase II SIMPLE measurements, comprising two run stages of 15 superheated droplet detectors each, with the second stage including an improved neutron shielding. The analyses include a refined signal analysis, and revised nucleation efficiency based on a reanalysis of previously reported monochromatic neutron irradiations. The combined results yield a contour minimum of σp=5.7×10-3pb at 35GeV/c2 in the spin-dependent sector of weakly interacting massive particle (WIMP) proton interactions, the most restrictive to date for MW≤60GeV/c2 from a direct search experiment and overlapping, for the first time, with results previously obtained only indirectly. In the spin-independent sector, a minimum of 4.7×10-6pb at 35GeV/c2 is achieved, with the exclusion contour challenging a significant part of the light mass WIMP region of current interest.

  10. Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.

    PubMed

    Morrone, A; Tylee, K L; Al-Sayed, M; Brusius-Facchin, A C; Caciotti, A; Church, H J; Coll, M J; Davidson, K; Fietz, M J; Gort, L; Hegde, M; Kubaski, F; Lacerda, L; Laranjeira, F; Leistner-Segal, S; Mooney, S; Pajares, S; Pollard, L; Ribeiro, I; Wang, R Y; Miller, N

    2014-06-01

    Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles have a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided. Copyright © 2014. Published by Elsevier Inc.

  11. Demonstration Results of the Triband, Multi-Beam Airborne Telemetry Phased Array (AirPA) System

    DTIC Science & Technology

    2015-03-01

    AirPA Phase 3 test event in September 2014, the element level digital beamforming phased array was successfully demonstrated at Edwards Air Force...Base in L-band, S-band, and C-band at a technology readiness level of 6. The system tracked both ground and air mobile transmitters using ARTM Tier 0...Phased Array, antenna, digital beam-forming, beamforming , DBF, L-band, S-band, C-band, CTEIP, NAVAIR 16. SECURITY CLASSIFICATION OF

  12. Mineralizing urban net-zero water treatment: Phase II field results and design recommendations.

    PubMed

    Gassie, Lucien W; Englehardt, James D; Wang, Jian; Brinkman, Nichole; Garland, Jay; Gardinali, Piero; Guo, Tianjiao

    2016-11-15

    Net-zero water (NZW) systems, or water management systems achieving high recycling rates and low residuals generation so as to avoid water import and export, can also conserve energy used to heat and convey water, while economically restoring local eco-hydrology. However, design and operating experience are extremely limited. The objective of this paper is to present the results of the second phase of operation of an advanced oxidation-based NZW pilot system designed, constructed, and operated for a period of two years, serving an occupied four-person apartment. System water was monitored, either continuously or thrice daily, for routine water quality parameters, minerals, and MicroTox(®) in-vitro toxicity, and intermittently for somatic and male-specific coliphage, adenovirus, Cryptosporidium, Giardia, emerging organic constituents (non-quantitative), and the Florida drinking water standards. All 115 drinking water standards with the exception of bromate were met in this phase. Neither virus nor protozoa were detected in the treated water, with the exception of measurement of adenovirus genome copies attributed to accumulation of inactive genetic material in hydraulic dead zones. Chemical oxygen demand was mineralized to <0.7 mg/L, and all but six of 1006 emerging organic constituents analyzed were either undetected or removed >90% in treatment. Total dissolved solids were maintained at ∼500 mg/L at steady state, partially through aerated aluminum electrocoagulation. Bromate accumulation is projected to be controlled by aluminum electrocoagulation with separate disposal of backwash water. Further development of such systems and their automated/remote process control systems is recommended. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial.

    PubMed

    Motzer, Robert J; Rini, Brian I; McDermott, David F; Redman, Bruce G; Kuzel, Timothy M; Harrison, Michael R; Vaishampayan, Ulka N; Drabkin, Harry A; George, Saby; Logan, Theodore F; Margolin, Kim A; Plimack, Elizabeth R; Lambert, Alexandre M; Waxman, Ian M; Hammers, Hans J

    2015-05-01

    Nivolumab is a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody that restores T-cell immune activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned (blinded ratio of 1:1:1) to nivolumab 0.3, 2, or 10 mg/kg intravenously once every 3 weeks. The primary objective was to evaluate the dose-response relationship as measured by progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), and safety. A total of 168 patients were randomly assigned to the nivolumab 0.3- (n = 60), 2- (n = 54), and 10-mg/kg (n = 54) cohorts. One hundred eighteen patients (70%) had received more than one prior systemic regimen. Median PFS was 2.7, 4.0, and 4.2 months, respectively (P = .9). Respective ORRs were 20%, 22%, and 20%. Median OS was 18.2 months (80% CI, 16.2 to 24.0 months), 25.5 months (80% CI, 19.8 to 28.8 months), and 24.7 months (80% CI, 15.3 to 26.0 months), respectively. The most common treatment-related adverse event (AE) was fatigue (24%, 22%, and 35%, respectively). Nineteen patients (11%) experienced grade 3 to 4 treatment-related AEs. Nivolumab demonstrated antitumor activity with a manageable safety profile across the three doses studied in mRCC. No dose-response relationship was detected as measured by PFS. These efficacy and safety results in mRCC support study in the phase III setting. © 2014 by American Society of Clinical Oncology.

  14. Phase I Clinical Trial Results of Auranofin, a Novel Antiparasitic Agent

    PubMed Central

    Capparelli, Edmund V.; Bricker-Ford, Robin; Rogers, M. John; McKerrow, James H.

    2016-01-01

    ABSTRACT Under an NIH priority to identify new drugs to treat class B parasitic agents, we performed high-throughput screens, which identified the activity of auranofin (Ridaura) against Entamoeba histolytica and Giardia intestinalis, major causes of water- and foodborne outbreaks. Auranofin, an orally administered, gold (Au)-containing compound that was approved by the FDA in 1985 for treatment of rheumatoid arthritis, was effective in vitro and in vivo against E. histolytica and both metronidazole-sensitive and -resistant strains of Giardia. We now report the results of an NIH-sponsored phase I trial to characterize the pharmacokinetics (PK) and safety of auranofin in healthy volunteers using modern techniques to measure gold levels. Subjects received orally 6 mg (p.o.) of auranofin daily, the recommended dose for rheumatoid arthritis, for 7 days and were followed for 126 days. Treatment-associated adverse events were reported by 47% of the subjects, but all were mild and resolved without treatment. The mean gold maximum concentration in plasma (Cmax) at day 7 was 0.312 μg/ml and the half-life (t1/2) 35 days, so steady-state blood levels would not be reached in short-term therapy. The highest concentration of gold, 13 μM (auranofin equivalent), or more than 25× the 50% inhibitory concentration (IC50) for E. histolytica and 4× that for Giardia, was in feces at 7 days. Modeling of higher doses (9 and 21 mg/day) was performed for systemic parasitic infections, and plasma gold levels of 0.4 to 1.0 μg/ml were reached after 14 days of treatment at 21 mg/day. This phase I trial supports the idea of the safety of auranofin and provides important PK data to support its potential use as a broad-spectrum antiparasitic drug. (This study has been registered at ClinicalTrials.gov under identifier NCT02089048.) PMID:27821451

  15. Water vapour tomography using GPS phase observations: Results from the ESCOMPTE experiment

    NASA Astrophysics Data System (ADS)

    Nilsson, T.; Gradinarsky, L.; Elgered, G.

    2007-10-01

    Global Positioning System (GPS) tomography is a technique for estimating the 3-D structure of the atmospheric water vapour using data from a dense local network of GPS receivers. Several current methods utilize estimates of slant wet delays between the GPS satellites and the receivers on the ground, which are difficult to obtain with millimetre accuracy from the GPS observations. We present results of applying a new tomographic method to GPS data from the Expériance sur site pour contraindre les modèles de pollution atmosphérique et de transport d'emissions (ESCOMPTE) experiment in southern France. This method does not rely on any slant wet delay estimates, instead it uses the GPS phase observations directly. We show that the estimated wet refractivity profiles estimated by this method is on the same accuracy level or better compared to other tomographic methods. The results are in agreement with earlier simulations, for example the profile information is limited above 4 km.

  16. Controversial results of therapy with mesenchymal stem cells in the acute phase of canine distemper disease.

    PubMed

    Pinheiro, A O; Cardoso, M T; Vidane, A S; Casals, J B; Passarelli, D; Alencar, A L F; Sousa, R L M; Fantinato-Neto, P; Oliveira, V C; Lara, V M; Ambrósio, C E

    2016-05-23

    Distemper disease is an infectious disease reported in several species of domestic and wild carnivores. The high mortality rate of animals infected with canine distemper virus (CDV) treated with currently available therapies has driven the study of new efficacious treatments. Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic option for many degenerative, hereditary, and inflammatory diseases. Therefore, the aim of this study was to characterize stem cells derived from the canine fetal olfactory epithelium and to assess the systemic response of animals infected with CDV to symptomatic therapy and treatment with MSCs. Eight domestic mongrel dogs (N = 8) were divided into two groups: support group (SG) (N = 5) and support group + cell therapy (SGCT) (N = 3), which were monitored over 15 days. Blood samples were collected on days 0, 6, 9, 12, and 15 to assess blood count and serum biochemistry (urea, creatinine, alanine transferase, alkaline phosphatase, gamma-glutamyl transferase, total protein, albumin, and globulin), and urine samples were obtained on days 0 and 15 for urinary evaluation (urine I). The results showed a high mortality rate (SG = 4 and SGCT = 2), providing inadequate data on the clinical course of CDV infection. MSC therapy resulted in no significant improvement when administered during the acute phase of canine distemper disease, and a prevalence of animals with high mortality rate was found in both groups due to the severity of symptoms.

  17. Test results of the Electric Vehicle Field-Laboratory Correspondence Program, phase 1 report

    NASA Astrophysics Data System (ADS)

    MacDowall, R. D.

    1987-12-01

    During the past decade a signficant number of vehicles, batteries, and powertrain components have been evaluated by the US Department of Energy (DOE) Electric and Hybrid Vehicle Program. These evaluation tests have been performed in dynamometer laboratories, on test tracks, and on the road under actual field operating conditions. Previous DOE-funded programs have developed several computer models which simulate electric vehicle performance over a wide range of operating conditions. This report presents the results of tests performed by EG and G Idaho, Inc., at the Idaho National Engineering Laboratory (INEL). The primary objective of the Electric Vehicle Field-Laboratory Correspondence Program is to significantly enhance the ability to predict field performance from laboratory test results, and to predict the behavior of vehicle systems not yet fabricated. A secondary objective of this program is to obtain real-time based data with the INEL Portable Data Acquisition system (PDAS) which can then be compared to the event-based test data acquired using the Versatile Data Acquisition System (VDAS). The VDAS-to-PDAS comparisons from these tests indicate the relative strengths and limitations of these rather different approaches to in-vehicle acquisition of engineering data. The conclusions of this first phase report indicate that the corresondence among the data acquisition systems was comparable to test-to-test repeatability, and that the energy consumption values matched closely among dynamometer, track, and tightly controlled road tests.

  18. DARPA/AFRL Smart Wing Phase 2 wind tunnel test results

    NASA Astrophysics Data System (ADS)

    Scherer, Lewis B.; Martin, C. A.; Sanders, Brian P.; West, Mark N.; Pinkerton-Florance, Jennifer L.; Wieseman, Carol D.; Burner, Alpheus W.; Fleming, Gary A.

    2002-07-01

    Northrop Grumman Corporation built and twice tested a 30 percent scale wind tunnel model of a proposed uninhabited combat air vehicle under the DARPA/AFRL Smart Materials and Structures Development - Smart Wing Phase 2 program to demonstrate the applicability of smart control surfaces on advanced aircraft configurations. The model constructed was a full span, sting mounted model with smart leading and trailing edge control surfaces on the right wing and conventional, hinged trailing edge control surfaces on the left wing. Among the performance benefits that were quantified were increased pitching moment, increased rolling moment and improved pressure distribution of the smart wing over the conventional wing. This paper present an overview of the result from the wind tunnel test performed at NASA Langley Research Center's Transonic Dynamic Tunnel in March 2000 and May 2001. Successful results included: (1) improved aileron effectiveness at high dynamic pressures, (2) demonstrated improvements in lateral and longitudinal effectiveness with smooth contoured smart trailing edge over conventional hinged control surfaces, (3) chordwise and spanwise shape control of the smart trailing edge control surface, and (4) smart trailing edge control surface deflection rates over 80 deg/sec.

  19. Pd-Ag chronology of volatile depletion, crystallization and shock in the Muonionalusta IVA iron meteorite and implications for its parent body

    NASA Astrophysics Data System (ADS)

    Horan, M. F.; Carlson, R. W.; Blichert-Toft, J.

    2012-10-01

    Muonionalusta, a Group IVA iron meteorite, was analyzed for its 107Pd-107Ag isotope systematics by multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) in order to better constrain the initial Solar System abundance of 107Pd and to provide high resolution chronology of the evolution of its parent body. Six metal samples from Muonionalusta yield Ag abundances between 0.1012 and 1.461 ng/g, 107Ag/109Ag between 1.131 and 1.805, with 108Pd/109Ag ratios of 2201 to 52,300. The metal Pd/Ag and Ag isotopic data are correlated with a slope corresponding to a 107Pd/108Pd of (2.15±0.30)×10-5. If the Pd-Ag and Pb-Pb isotope systems closed at the same time in Muonionalusta, i.e., 2-3 Ma after CAI formation, then an initial Solar System ratio of 107Pd/108Pd=(2.8±0.5)×10-5 can be inferred. One troilite sample contains 8.478 ng/g Ag and has a 107Ag/109Ag ratio of 1.0833; its Pd concentration is 205.2 ng/g corresponding to a low 108Pd/109Ag of 13.56. The Pd-Ag results for this troilite plot near the extrapolation of the line passing through the metal points and define an initial 107Ag/109Ag that is substantially higher than chondritic, indicating that Muonionalusta formed from a precursor with high Pd/Ag. Pd and Ag concentrations in Muonionalusta metal suggest fractional crystallization from a source having Pd/Ag>4500, but the initial Ag isotopic composition for Muonionalusta troilite limits the duration of the high Pd/Ag to an interval of ≤0.6 Ma before cooling to closure of the Pd-Ag system. This result suggests that depletion of Ag and other volatile elements occurred shortly before accretion and cooling of the IVA parent body, and may have been associated with violent disruption of a progenitor to the IVA parent. Another troilite sample, its chromite inclusions and adjacent metal were isotopically homogenized locally after 107Pd had decayed, possibly by a later episode of shock >50 Ma after Solar System formation.

  20. Concomitant chemoradiotherapy using carboplatin, tegafur-uracil and leucovorin for stage III and IV head-and-neck cancer: results of GORTEC Phase II study.

    PubMed

    Fesneau, Melanie; Pointreau, Yoann; Chapet, Sophie; Martin, Laurent; Pommier, Pascal; Alfonsi, Marc; Laguerre, Brigitte; Feham, Nasreddine; Berger, Christine; Garaud, Pascal; Calais, Gilles

    2010-01-01

    Concomitant chemoradiotherapy is the standard treatment of locally advanced, nonresectable, head-and-neck squamous cell carcinoma. However, the optimal chemotherapy regimen is still controversial. The objective of this Phase II study was to evaluate the feasibility and efficacy of a concomitant treatment using tegafur-uracil, leucovorin, carboplatin, and radiotherapy. A total of 77 patients with head-and-neck squamous cell carcinoma Stage III and IVA were enrolled between October 2003 and July 2005. Of the 77 patients, 72 were eligible. They were treated with tegafur-uracil (300 mg/m(2)/d) and leucovorin (75 mg/d) from Days 1 to 19 and from Days 29 to 47 and carboplatin (70 mg/m(2) intravenously for 4 consecutive days), in three cycles every 21 days. Conventional radiotherapy was delivered to a total dose of 70 Gy in 35 fractions. With a mean follow-up of 22.8 months, the 3-year locoregional control, overall survival and disease-free survival actuarial rate was 33.1%, 41.9%, and 27.2%, respectively. The compliance of the treatment was correct. The main acute toxicity was mucositis, with 62% Grade 3-4. Three patients (4.2%) died of acute toxicity. The incidence and severity of late toxicity was acceptable, with 32% Grade 3 and no Grade 4 toxicity. The protocol of concomitant chemoradiotherapy using tegafur-uracil, leucovorin, and carboplatin for locally advanced unresectable head-and-neck squamous cell carcinoma is feasible. The compliance was correct. The incidence and severity of the acute and late toxicities were acceptable, but not improved. The efficacy of this regimen seems equivalent to the main protocols of concurrent chemoradiotherapy. It represents a possible alternative for patients without an intravenous catheter.

  1. Results of two-phase natural circulation in hot-leg U-bend simulation experiments

    SciTech Connect

    Ishii, M.; Lee, S.Y.; Abou El-Seoud, S.

    1987-01-01

    In order to study the two-phase natural circulation and flow termination during a small break loss of coolant accident in LWR, simulation experiments have been performed using two different thermal-hydraulic loops. The main focus of the experiment was the two-phase flow behavior in the hot-leg U-bend typical of BandW LWR systems. The first group of experiments was carried out in the nitrogen gas-water adiabatic simulation loop and the second in the Freon 113 boiling and condensation loop. Both of the loops have been designed as a flow visualization facility and built according to the two-phase flow scaling criteria developed under this program. The nitrogen gas-water system has been used to isolate key hydrodynamic phenomena such as the phase distribution, relative velocity between phases, two-phase flow regimes and flow termination mechanisms, whereas the Freon loop has been used to study the effect of fluid properties, phase changes and coupling between hydrodynamic and heat transfer phenomena. Significantly different behaviors have been observed due to the non-equilibrium phase change phenomena such as the flashing and condensation in the Freon loop. The phenomena created much more unstable hydrodynamic conditions which lead to cyclic or oscillatory flow behaviors.

  2. Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial

    PubMed Central

    Van Coevorden, Frits; Punt, Cornelis J. A.; Pierie, Jean-Pierre E. N.; Borel-Rinkes, Inne; Ledermann, Jonathan A.; Poston, Graeme; Bechstein, Wolf; Lentz, Marie-Ange; Mauer, Murielle; Folprecht, Gunnar; Van Cutsem, Eric; Ducreux, Michel; Nordlinger, Bernard

    2017-01-01

    Background: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. Methods: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n < 10 and no extrahepatic disease) received systemic treatment alone or systemic treatment plus aggressive local treatment by radiofrequency ablation ± resection. Previously, we reported that the primary end point (30-month overall survival [OS] > 38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. Results: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. Conclusions: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases. PMID:28376151

  3. Promising short-term clinical results of the cementless Oxford phase III medial unicondylar knee prosthesis.

    PubMed

    van Dorp, Karin B; Breugem, Stefan Jm; Bruijn, Daniël J; Driessen, Marcel Jm

    2016-04-18

    To investigate the short-term clinical results of the Oxford phase III cementless medial unicondylar knee prosthesis (UKP) compared to the cemented medial UKP. We conducted a cross-sectional study in a tertairy orthopedic centre between the period of May 2010 and September 2012. We included 99 medial UKP in 97 patients and of these UKP, 53 were cemented and 46 were cementless. Clinical outcome was measured using a questionnaire, containing a visual analogue scale (VAS) for pain, Oxford Knee score, Kujala score and SF-12 score. Knee function was tested using the American Knee Society score. Complications, reoperations and revisions were recorded. Statistical significance was defined as a P value < 0.05. In a mean follow-up time of 19.5 mo, three cemented medial UKP were revised to a total knee prosthesis. Reasons for revision were malrotation of the tibial component, aseptic loosening of the tibial component and progression of osteoarthritis in the lateral- and patellofemoral compartment. In five patients a successful reoperation was performed, because of impingement or (sub)luxation of the polyethylene bearing. Patients with a reoperation were significant younger than patients in the primary group (56.7 vs 64.0, P = 0.01) and were more likely to be male (85.7% vs 38.8%, P = 0.015). Overall the cementless medial UKP seems to perform better, but the differences in clinical outcome are not significant; a VAS pain score of 7.4 vs 11.7 (P = 0.22), an Oxford Knee score of 43.3 vs 41.7 (P = 0.27) and a Kujala score of 79.6 vs 78.0 (P = 0.63). The American Knee Society scores were slightly better in the cementless group with 94.5 vs 90.2 (P = 0.055) for the objective score and 91.2 vs 87.8 (P = 0.25) for the subjective score. The cementless Oxford phase III medial UKP shows good short-term clinical results, when used in a specialist clinic by an experienced surgeon.

  4. NASA's Atmospheric Effects of Aviation Project: Results of the August 1999 Aerosol Measurement Intercomparison Workshop, Laboratory Phase

    NASA Technical Reports Server (NTRS)

    Cofer, W. Randy, III; Anderson, Bruce E.; Connors, V. S.; Wey, C. C.; Sanders, T.; Twohy, C.; Brock, C. A.; Winstead, E. L.; Pui, D.; Chen, Da-Ren

    2001-01-01

    During August 1-14, 1999, NASA's Atmospheric Effects of Aviation Project (AEAP) convened a workshop at the NASA Langley Research Center to try to determine why such a wide variation in aerosol emissions indices and chemical and physical properties have been reported by various independent AEAP-supported research teams trying to characterize the exhaust emissions of subsonic commercial aircraft. This workshop was divided into two phases, a laboratory phase and a field phase. The laboratory phase consisted of supplying known particle number densities (concentrations) and particle size distributions to a common manifold for the participating research teams to sample and analyze. The field phase was conducted on an aircraft run-up pad. Participating teams actually sampled aircraft exhaust generated by a Langley T-38 Talon aircraft at 1 and 9 m behind the engine at engine powers ranging from 48 to 100 percent. Results from the laboratory phase of this intercomparison workshop are reported in this paper.

  5. Intraoperative Radiotherapy in Early-Stage Breast Cancer: Results of the Montpellier Phase II Trial

    SciTech Connect

    Lemanski, Claire; Azria, David; Gourgon-Bourgade, Sophie; Gutowski, Marian; Rouanet, Phillippe; Saint-Aubert, Bernard; Ailleres, Norbert; Fenoglietto, Pascal; Dubois, Jean-Bernard

    2010-03-01

    Purpose: We recently presented the intraoperative radiotherapy (IORT) technique given as a reliable alternative to conventional boost radiation after breast-conserving surgery. The low crude numbers of recurrence in elderly patients led us to investigate the feasibility and the efficacy of this procedure as a sole treatment. Methods and Materials: We included 94 patients older than 65 years in this phase II trial. Among them, 42 patients presented with all the inclusion criteria, i.e., stages pT0 to pT1 and pN0, ductal invasive unifocal carcinoma, and tumor-free margin of >2 mm. IORT was delivered using a dedicated linear accelerator. One 21-Gy fraction was prescribed and specified at the 90% isodose, using electrons. In vivo dosimetry was performed for all patients. The primary endpoint was the quality index. Secondary endpoints were quality of life, local recurrences, cosmetic results, and specific and overall rates of survival. Results: The median follow-up was 30 months (range, 12-49 months), and median age was 72 years (range, 66-80 years). The median tumor diameter was 10 mm. All patients received the total prescribed dose. No acute grade 3 toxicities were observed. Endpoints for all but one patient corresponded to acceptable quality index criteria. Pretreatment quality-of-life scores were maximal, and no significant decrease was observed during follow-up. Cosmesis was good to excellent at 6 months. Two patients experienced recurrence but underwent salvage mastectomy. Conclusion: Our results confirm that exclusive partial-breast IORT is feasible for treating early-stage breast cancer in the elderly. IORT may be considered an alternative treatment for a selected population and offers a safe one-step treatment.

  6. Offshore Code Comparison Collaboration, Continuation: Phase II Results of a Floating Semisubmersible Wind System: Preprint

    SciTech Connect

    Robertson, A.; Jonkman, J.; Musial, W.; Vorpahl, F.; Popko, W.

    2013-11-01

    Offshore wind turbines are designed and analyzed using comprehensive simulation tools that account for the coupled dynamics of the wind inflow, aerodynamics, elasticity, and controls of the turbine, along with the incident waves, sea current, hydrodynamics, and foundation dynamics of the support structure. The Offshore Code Comparison Collaboration (OC3), which operated under the International Energy Agency (IEA) Wind Task 23, was established to verify the accuracy of these simulation tools [1]. This work was then extended under the Offshore Code Comparison Collaboration, Continuation (OC4) project under IEA Wind Task 30 [2]. Both of these projects sought to verify the accuracy of offshore wind turbine dynamics simulation tools (or codes) through code-to-code comparison of simulated responses of various offshore structures. This paper describes the latest findings from Phase II of the OC4 project, which involved the analysis of a 5-MW turbine supported by a floating semisubmersible. Twenty-two different organizations from 11 different countries submitted results using 24 different simulation tools. The variety of organizations contributing to the project brought together expertise from both the offshore structure and wind energy communities. Twenty-one different load cases were examined, encompassing varying levels of model complexity and a variety of metocean conditions. Differences in the results demonstrate the importance and accuracy of the various modeling approaches used. Significant findings include the importance of mooring dynamics to the mooring loads, the role nonlinear hydrodynamic terms play in calculating drift forces for the platform motions, and the difference between global (at the platform level) and local (at the member level) modeling of viscous drag. The results from this project will help guide development and improvement efforts for these tools to ensure that they are providing the accurate information needed to support the design and

  7. Evaluation of fine-particle catalysts: Activity testing results and phase identification using Mossbauer spectroscopy

    SciTech Connect

    Stohl, F.V.; Diegert, K.V.; Goodnow, D.; Rao, K.R.P.M.; Huggins, F.; Huffman, G.P.

    1994-10-01

    To evaluate and compare the activities/selectivities of fine- particle size catalysts being developed in the DOE/PETC Advanced Research (AR) Coal Liquefaction program by using standard coal liquefaction activity test procedures. Previously reported results have described the standard test procedure that was developed at Sandia to evaluate fine-particle size iron catalysts being developed in DOE/PETC`s AR Coal Liquefaction Program. This test uses DECS-17 Blind Canyon Coal, phenanthrene as the reaction solvent, and a factorial experimental design that enables evaluation of a catalyst over ranges of temperature (350 to 400{degrees}C), time (20 to 60 minutes), and catalyst loading (0 to 1 wt% on a dmmf coal basis). Testing has been performed on Pacific Northwest Laboratories` (PNL) 6-line ferrihydrite catalyst. Results showed that this catalyst is more active than the University of Pittsburgh`s sulfated iron oxide catalyst that was evaluated previously. PNL has also produced two additional batches of catalyst in an effort to optimize their preparation procedures for larger batches. Sandia has observed significant differences in activities among these three catalysts; these differences might be due to particle size effects, the type of drying procedure, or the amount of moisture present. Mossbauer characterization of the iron phases in the coal, catalyst precursors, and tetrahydrofuran (THF) insoluble material from liquefaction reactions has been performed on the University of Pittsburgh`s catalyst and the first PNL catalyst that was tested at Sandia. The Mossbauer results were obtained at the University of Kentucky and will be presented. Future work will include testing additional catalysts being developed in the AR Coal Liquefaction Program, developing procedures to characterize reaction products, and determining the kinetics of the reactions.

  8. Hypolipidemic effects of acute and sub-chronic administration of an aqueous extract of Ajuga iva L. whole plant in normal and diabetic rats.

    PubMed

    El-Hilaly, Jaouad; Tahraoui, Adil; Israili, Zafar H; Lyoussi, Badiâa

    2006-05-24

    Diabetes is often accompanied by lipid abnormalities, which contribute significantly to cardiovascular (CV) morbidity and mortality in diabetic patients. The plant Ajuga iva (L.) Schreiber (Labiatea) is used in the treatment of diabetes in Moroccan folk medicine. Previously, we have demonstrated potent hypoglycemic activity and relatively non-toxic nature of a lyophilized aqueous extract of the whole plant (AI-extract) in normal (normoglycemic) and streptozotocin (STZ)-diabetic rats. In this study, we examined the AI-extract for its possible lipid-lowering activity in normal and STZ-diabetic rats. Taurine (TR) and glibenclamide (GLB) were used as reference substances. As shown previously, the AI-extract (10 mg/kg; oral) reduced plasma glucose levels after acute (single) and sub-chronic (3 weeks) dosing both in normal and diabetic rats. In normal rats, single and repeated oral administration of the AI-extract, at a dose of 10 mg/kg produced a small but significant decrease in plasma CHL levels (P<0.05). A single dose of the AI-extract did not produce a significant change in plasma TG, but sub-chronic dosing (for up to 21 days) caused a significant decrease in plasma TG (P<0.05). In STZ-diabetic rats, a single dose as well as repeated (3 weeks) treatment with the AI-extract produced a significant decrease in plasma CHL (P<0.01), and triglyceride (P<0.01) levels. The AI-extract also prevented weight loss in the diabetic animals. In summary, an aqueous extract of the Ajuga iva whole plant showed hypolipidemic activity, in addition to its hypoglycemic effect in normoglycemic and diabetic rats. In view of the hypoglycemic and hypolipidemic activity, and its relatively non-toxic nature (shown previously), Ajuga iva may be a candidate for development as an anti-diabetic agent in humans. Further studies are warranted to confirm our results and fractionate the AI-extract to isolate and identify the active principle(s), and to determine the exact mechanism(s) of action.

  9. Euclid near infrared spectrophotometer instrument concept and first test results at the end of phase B

    NASA Astrophysics Data System (ADS)

    Maciaszek, Thierry; Ealet, Anne; Jahnke, Knud; Prieto, Eric; Barbier, Rémi; Mellier, Yannick; Costille, Anne; Ducret, Franck; Fabron, Christophe; Gimenez, Jean-Luc; Grange, Robert; Martin, Laurent; Rossin, Christelle; Pamplona, Tony; Vola, Pascal; Clémens, Jean Claude; Smadja, Gérard; Amiaux, Jérome; Barrière, Jean Christophe; Berthe, Michel; De Rosa, Adriano; Franceschi, Enrico; Morgante, Gianluca; Trifoglio, Massimo; Valenziano, Luca; Bonoli, Carlotta; Bortoletto, Favio; D'Alessandro, Maurizio; Corcione, Leonardo; Ligori, Sebastiano; Garilli, Bianca; Riva, Marco; Grupp, Frank; Vogel, Carolin; Hormuth, Felix; Seidel, Gregor; Wachter, Stefanie; Diaz, Jose Javier; Grañena, Ferran; Padilla, Cristobal; Toledo, Rafael; Lilje, Per B.; Solheim, Bjarte G. B.; Toulouse-Aastrup, Corinne; Andersen, Michael; Holmes, Warren; Israelsson, Ulf; Seiffert, Michael; Weber, Carissa; Waczynski, Augustyn; Laureijs, René J.; Racca, Giuseppe; Salvignol, Jean-Christophe; Strada, Paolo

    2014-08-01

    The Euclid mission objective is to understand why the expansion of the Universe is accelerating by mapping the geometry of the dark Universe by investigating the distance-redshift relationship and tracing the evolution of cosmic structures. The Euclid project is part of ESA's Cosmic Vision program with its launch planned for 2020. The NISP (Near Infrared Spectro-Photometer) is one of the two Euclid instruments and is operating in the near-IR spectral region (0.9-2μm) as a photometer and spectrometer. The instrument is composed of: - a cold (135K) optomechanical subsystem consisting of a SiC structure, an optical assembly (corrector and camera lens), a filter wheel mechanism, a grism wheel mechanism, a calibration unit and a thermal control system - a detection subsystem based on a mosaic of 16 Teledyne HAWAII2RG cooled to 95K with their front-end readout electronic cooled to 140K, integrated on a mechanical focal plane structure made with Molybdenum and Aluminum. The detection subsystem is mounted on the optomechanical subsystem structure - a warm electronic subsystem (280K) composed of a data processing / detector control unit and of an instrument control unit that interfaces with the spacecraft via a 1553 bus for command and control and via Spacewire links for science data This presentation describes the architecture of the instrument at the end of the phase B (Preliminary Design Review), the expected performance, the technological key challenges and preliminary test results obtained on a detection system demonstration model.

  10. Development and first results of the Yale PIXeY two-phase xenon detector

    NASA Astrophysics Data System (ADS)

    Destefano, Nicholas E.; Bernard, Ethan; Edwards, Blair; Gai, Moshe; Horn, Markus; Larsen, Nicole; McKinsey, Daniel; Tennyson, Brian; Wahl, Christopher

    2013-09-01

    PIXeY (Particle Identification in Xenon at Yale) is a two-phase (liquid/gas) xenon prototype time projection chamber with 3 kg active mass. PIXeY was built to optimize energy resolution and gamma/neutron discrimination, with a number of technological improvements over previous work. Parallel-wire grids, which control the drift and proportionalscintillation fields, are optimized both for light collection efficiency and field uniformity. High quantum efficiency Hamamatsu R8778 PMTs, high-reflectivity Teflon walls, and charge-light anti-correlation techniques are also incorporated. The first run of the detector has concluded, where all systems were tested both using LED calibration methods as well as using sources for calibration and spectral measurements. Ultimately our results were limited by PMT calibration issues, low light collection caused by saturation, and low drift fields constrained by high voltage hardware. The second run of the detector is currently underway with several improved components. The feedthroughs for higher voltages have improved to allow a much higher operating voltage, new PMT bases for more stable operation have been installed, and three new grids with transparencies between 92% and 97% have been added. Once the energy resolution studies have concluded, PIXeY will serve as a platform for future improvements, including multiple optical volumes and single wire readout for R&D on gamma-ray imaging.

  11. Surrogate/spent fuel sabotage : aerosol ratio test program and Phase 2 test results.

    SciTech Connect

    Borek, Theodore Thaddeus III; Thompson, N. Slater; Sorenson, Ken Bryce; Hibbs, R.S.; Nolte, Oliver; Molecke, Martin Alan; Autrusson, Bruno; Young, F. I.; Koch, Wolfgang; Brochard, Didier; Pretzsch, Gunter Guido; Lange, Florentin

    2004-05-01

    A multinational test program is in progress to quantify the aerosol particulates produced when a high energy density device, HEDD, impacts surrogate material and actual spent fuel test rodlets. This program provides needed data that are relevant to some sabotage scenarios in relation to spent fuel transport and storage casks, and associated risk assessments; the program also provides significant political benefits in international cooperation. We are quantifying the spent fuel ratio, SFR, the ratio of the aerosol particles released from HEDD-impacted actual spent fuel to the aerosol particles produced from surrogate materials, measured under closely matched test conditions. In addition, we are measuring the amounts, nuclide content, size distribution of the released aerosol materials, and enhanced sorption of volatile fission product nuclides onto specific aerosol particle size fractions. These data are crucial for predicting radiological impacts. This document includes a thorough description of the test program, including the current, detailed test plan, concept and design, plus a description of all test components, and requirements for future components and related nuclear facility needs. It also serves as a program status report as of the end of FY 2003. All available test results, observations, and analyses - primarily for surrogate material Phase 2 tests using cerium oxide sintered ceramic pellets are included. This spent fuel sabotage - aerosol test program is coordinated with the international Working Group for Sabotage Concerns of Transport and Storage Casks, WGSTSC, and supported by both the U.S. Department of Energy and Nuclear Regulatory Commission.

  12. The Geoengineering Model Intercomparison Project Phase 6 (GeoMIP6): simulation design and preliminary results

    NASA Astrophysics Data System (ADS)

    Kravitz, B.; Robock, A.; Tilmes, S.; Boucher, O.; English, J. M.; Irvine, P. J.; Jones, A.; Lawrence, M. G.; MacCracken, M.; Muri, H.; Moore, J. C.; Niemeier, U.; Phipps, S. J.; Sillmann, J.; Storelvmo, T.; Wang, H.; Watanabe, S.

    2015-06-01

    We present a suite of new climate model experiment designs for the Geoengineering Model Intercomparison Project (GeoMIP). This set of experiments, named GeoMIP6 (to be consistent with the Coupled Model Intercomparison Project Phase 6), builds on the previous GeoMIP simulations, and has been expanded to address several further important topics, including key uncertainties in extreme events, the use of geoengineering as part of a portfolio of responses to climate change, and the relatively new idea of cirrus cloud thinning to allow more longwave radiation to escape to space. We discuss experiment designs, as well as the rationale for those designs, showing preliminary results from individual models when available. We also introduce a new feature, called the GeoMIP Testbed, which provides a platform for simulations that will be performed with a few models and subsequently assessed to determine whether the proposed experiment designs will be adopted as core (Tier 1) GeoMIP experiments. This is meant to encourage various stakeholders to propose new targeted experiments that address their key open science questions, with the goal of making GeoMIP more relevant to a broader set of communities.

  13. The Geoengineering Model Intercomparison Project Phase 6 (GeoMIP6): simulation design and preliminary results

    NASA Astrophysics Data System (ADS)

    Kravitz, B.; Robock, A.; Tilmes, S.; Boucher, O.; English, J. M.; Irvine, P. J.; Jones, A.; Lawrence, M. G.; MacCracken, M.; Muri, H.; Moore, J. C.; Niemeier, U.; Phipps, S. J.; Sillmann, J.; Storelvmo, T.; Wang, H.; Watanabe, S.

    2015-10-01

    We present a suite of new climate model experiment designs for the Geoengineering Model Intercomparison Project (GeoMIP). This set of experiments, named GeoMIP6 (to be consistent with the Coupled Model Intercomparison Project Phase 6), builds on the previous GeoMIP project simulations, and has been expanded to address several further important topics, including key uncertainties in extreme events, the use of geoengineering as part of a portfolio of responses to climate change, and the relatively new idea of cirrus cloud thinning to allow more longwave radiation to escape to space. We discuss experiment designs, as well as the rationale for those designs, showing preliminary results from individual models when available. We also introduce a new feature, called the GeoMIP Testbed, which provides a platform for simulations that will be performed with a few models and subsequently assessed to determine whether the proposed experiment designs will be adopted as core (Tier 1) GeoMIP experiments. This is meant to encourage various stakeholders to propose new targeted experiments that address their key open science questions, with the goal of making GeoMIP more relevant to a broader set of communities.

  14. The Geoengineering Model Intercomparison Project Phase 6 (GeoMIP6): Simulation design and preliminary results

    DOE PAGES

    Kravitz, Benjamin S.; Robock, Alan; Tilmes, S.; ...

    2015-10-27

    We present a suite of new climate model experiment designs for the Geoengineering Model Intercomparison Project (GeoMIP). This set of experiments, named GeoMIP6 (to be consistent with the Coupled Model Intercomparison Project Phase 6), builds on the previous GeoMIP project simulations, and has been expanded to address several further important topics, including key uncertainties in extreme events, the use of geoengineering as part of a portfolio of responses to climate change, and the relatively new idea of cirrus cloud thinning to allow more long wave radiation to escape to space. We discuss experiment designs, as well as the rationale formore » those designs, showing preliminary results from individual models when available. We also introduce a new feature, called the GeoMIP Testbed, which provides a platform for simulations that will be performed with a few models and subsequently assessed to determine whether the proposed experiment designs will be adopted as core (Tier 1) GeoMIP experiments. In conclusion, this is meant to encourage various stakeholders to propose new targeted experiments that address their key open science questions, with the goal of making GeoMIP more relevant to a broader set of communities.« less

  15. The Geoengineering Model Intercomparison Project Phase 6 (GeoMIP6): Simulation design and preliminary results

    SciTech Connect

    Kravitz, Benjamin S.; Robock, Alan; Tilmes, S.; Boucher, Olivier; English, J. M.; Irvine, Peter J.; Jones, Andrew; Lawrence, M. G.; MacCracken, Michael C.; Muri, Helene O.; Moore, John C.; Niemeier, Ulrike; Phipps, Steven J.; Sillmann, Jana; Storelvmo, Trude; Wang, Hailong; Watanabe, Shingo

    2015-10-27

    We present a suite of new climate model experiment designs for the Geoengineering Model Intercomparison Project (GeoMIP). This set of experiments, named GeoMIP6 (to be consistent with the Coupled Model Intercomparison Project Phase 6), builds on the previous GeoMIP project simulations, and has been expanded to address several further important topics, including key uncertainties in extreme events, the use of geoengineering as part of a portfolio of responses to climate change, and the relatively new idea of cirrus cloud thinning to allow more long wave radiation to escape to space. We discuss experiment designs, as well as the rationale for those designs, showing preliminary results from individual models when available. We also introduce a new feature, called the GeoMIP Testbed, which provides a platform for simulations that will be performed with a few models and subsequently assessed to determine whether the proposed experiment designs will be adopted as core (Tier 1) GeoMIP experiments. In conclusion, this is meant to encourage various stakeholders to propose new targeted experiments that address their key open science questions, with the goal of making GeoMIP more relevant to a broader set of communities.

  16. Bubble Generation in a Flowing Liquid Medium and Resulting Two-Phase Flow in Microgravity

    NASA Technical Reports Server (NTRS)

    Pais, S. C.; Kamotani, Y.; Bhunia, A.; Ostrach, S.

    1999-01-01

    forming bubble decreases, as the superficial liquid velocity is in-creased. Furthermore, it is shown that the void fraction of the resulting two-phase flow increases with volumetric gas flow rate Q(sub d), pipe diameter and gas injection nozzle diameter, while they decrease with surrounding liquid flow. The important role played by flowing liquid in detaching bubbles in a reduced gravity environment is thus emphasized. We observe that the void fraction can be accurately controlled by using single nozzle gas injection, rather than by employing multiple port injection, since the later system gives rise to unpredictable coalescence of adjacent bubbles. It is of interest to note that empirical bubble size and corresponding void fraction are somewhat smaller for the co-flow geometry than the cross-flow configuration at similar flow conditions with similar pipe and nozzle diameters. In order to supplement the empirical data, a theoretical model is employed to study single bubble generation in the dynamic (Q(sub d) = 1 - 1000 cu cm/s) and bubbly flow regime within the framework of the co-flow configuration. This theoretical model is based on an overall force balance acting on the bubble during the two stages of generation, namely the expansion and the detachment stage. Two sets of forces, one aiding and the other inhibiting bubble detachment are identified. Under conditions of reduced gravity, gas momentum flux enhances, while the surface tension force at the air injection nozzle tip inhibits bubble detachment. In parallel, liquid drag and inertia can act as both attaching and detaching forces, depending on the relative velocity of the bubble with respect to the surrounding liquid. Predictions of the theoretical model compare well with our experimental results. However, at higher superficial liquid velocities, as the bubble loses its spherical form, empirical bubble size no longer matches the theoretical predictions. In summary, we have developed a combined experimental and

  17. Low-Frequency Foam Insulator (LOFFI) Accelerometer Mount Characterization Results and Analysis for Phase I (FY2013)

    DTIC Science & Technology

    2014-06-01

    Low-Frequency Foam Insulator (LOFFI) Accelerometer Mount Characterization Results and Analysis for Phase I (FY2013) by Andrew Drysdale...Proving Ground, MD 21005-5068 ARL-TR-6977 June 2014 Low-Frequency Foam Insulator (LOFFI) Accelerometer Mount Characterization Results...4. TITLE AND SUBTITLE Low-Frequency Foam Insulator (LOFFI) Accelerometer Mount Characterization Results and Analysis for Phase I (FY2013) 5a

  18. Results from the first preclinical CT scanner with grating based phase contrast and a rotating gantry

    SciTech Connect

    Bech, Martin; Tapfer, Arne; Velroyen, Astrid; Yaroshenko, Andre; Pauwels, Bart; Bruyndonckx, Peter; Liu Xuan; Sasov, Alexander; Mohr, Juergen; Walter, Marco; Pfeiffer, Franz

    2012-07-31

    After successful demonstrations of soft-tissue phase-contrast imaging with grating interferometers at synchrotron radiation sources and at laboratory based x-ray tubes, a first preclinical CT scanner with grating based phase contrast imaging modality has been constructed. The rotating gantry is equipped with a three-grating interferometer, a 50 watt tungsten anode source and a Hamamatsu flat panel detector. The total length of the interferometer is 45 cm, and the bed of the scanner is optimized for mice, with a scanning diameter of 35 mm. From one single scan both phase-contrast and standard attenuation based tomography can be attained, providing an overall gain in image contrast.

  19. Results from the first preclinical CT scanner with grating based phase contrast and a rotating gantry

    NASA Astrophysics Data System (ADS)

    Bech, Martin; Tapfer, Arne; Velroyen, Astrid; Yaroshenko, Andre; Pauwels, Bart; Bruyndonckx, Peter; Liu, Xuan; Sasov, Alexander; Mohr, Jürgen; Walter, Marco; Pfeiffer, Franz

    2012-07-01

    After successful demonstrations of soft-tissue phase-contrast imaging with grating interferometers at synchrotron radiation sources and at laboratory based x-ray tubes, a first preclinical CT scanner with grating based phase contrast imaging modality has been constructed. The rotating gantry is equipped with a three-grating interferometer, a 50 watt tungsten anode source and a Hamamatsu flat panel detector. The total length of the interferometer is 45 cm, and the bed of the scanner is optimized for mice, with a scanning diameter of 35 mm. From one single scan both phase-contrast and standard attenuation based tomography can be attained, providing an overall gain in image contrast.

  20. Chemoradiation Therapy and Ipilimumab in Treating Patients With Stages IB2-IIB or IIIB-IVA Cervical Cancer

    ClinicalTrials.gov

    2017-09-28

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Positive Para-Aortic Lymph Node; Positive Pelvic Lymph Node; Stage IB2 Cervical Cancer; Stage II Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  1. Combined 238U/235U and Pb Isotopics of Planetary Core Material: The Absolute Age of the IVA Iron Muonionalusta

    NASA Astrophysics Data System (ADS)

    Brennecka, G. A.; Amelin, Y.; Kleine, T.

    2016-08-01

    We report a measured 238U/235U for the IVA iron Muonionalusta. This measured value requires an age correction of ~7 Myr to the previously published Pb-Pb age. This has major implications for our understanding of planetary core formation and cooling.

  2. Cr-Bearing Inclusions in IVA Irons: Implication for Cr and Volatile Behaviors in the Metallic Cores

    NASA Astrophysics Data System (ADS)

    Isa, J.; McKeegan, K. D.; Wasson, J. T.

    2015-07-01

    We found inclusions that contribute to bulk Cr concentrations and found fO2 or fS2 changes during crystallization. O-isotope compositions of chromite are mass-dependently lighter than other IVA oxides. Also, we discovered a new mineral MnCr2S4.

  3. MRI and PET Imaging in Predicting Treatment Response in Patients With Stage IB-IVA Cervical Cancer

    ClinicalTrials.gov

    2017-06-27

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Cervical Undifferentiated Carcinoma; Recurrent Cervical Carcinoma; Stage IB2 Cervical Cancer; Stage II Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  4. Hypofractionated Postmastectomy Radiation Therapy Is Safe and Effective: First Results From a Prospective Phase II Trial.

    PubMed

    Khan, Atif J; Poppe, Matthew M; Goyal, Sharad; Kokeny, Kristine E; Kearney, Thomas; Kirstein, Laurie; Toppmeyer, Deborah; Moore, Dirk F; Chen, Chunxia; Gaffney, David K; Haffty, Bruce G

    2017-06-20

    Purpose Conventionally fractionated postmastectomy radiation therapy (PMRT) takes approximately 5 to 6 weeks. Data supporting hypofractionated PMRT is limited. We prospectively evaluated a short course of hypofractionated PMRT, in which therapy was completed in 15 treatment days. Patients and Methods We delivered PMRT at a dose of 36.63 Gy in 11 fractions of 3.33 Gy over 11 days to the chest wall and the draining regional lymph nodes, followed by an optional mastectomy scar boost of four fractions of 3.33 Gy. Our primary end point was freedom from any grade 3 or higher toxicities. We incorporated early stopping criteria on the basis of predefined toxicity thresholds. Results We enrolled 69 women with stage II to IIIa breast cancer, of whom 67 were eligible for analysis. After a median follow-up of 32 months, there were no grade 3 toxicities. There were 29 reported grade 2 toxicities, with grade 2 skin toxicities being the most frequent (16 of 67; 24%). There were two patients with isolated ipsilateral chest wall tumor recurrences (2 of 67; crude rate, 3%). Three-year estimated local recurrence-free survival was 89.2% (95% CI, 0.748 to 0.956). The 3-year estimated distant recurrence-free survival was 90.3% (95% CI, 0.797 to 0.956). Forty-one patients had chest wall reconstructions; three had expanders removed for infection before radiation therapy. The total rate of implant loss or failure was 24% (9 of 38), and the unplanned surgical correction rate was 8% (3 of 38), for a total complication rate of 32%. Conclusion To our knowledge, our phase II prospective study offers one of the shortest courses of PMRT reported, delivered in 11 fractions to the chest wall and nodes and 15 fractions inclusive of a boost. We demonstrated low toxicity and high local control with this schedule. On the basis of our data, we have designed a cooperative group phase III prospective, randomized trial of conventional versus hypofractionated PMRT that will activate soon.

  5. Sodium oxybate therapy provides multidimensional improvement in fibromyalgia: results of an international phase 3 trial

    PubMed Central

    Spaeth, Michael; Bennett, Robert M; Benson, Beverly A; Wang, Y Grace; Lai, Chinglin; Choy, Ernest H

    2012-01-01

    Background Fibromyalgia is characterised by chronic musculoskeletal pain and multiple symptoms including fatigue, multidimensional function impairment, sleep disturbance and tenderness. Along with pain and fatigue, non-restorative sleep is a core symptom of fibromyalgia. Sodium oxybate (SXB) is thought to reduce non-restorative sleep abnormalities. This study evaluated effects of SXB on fibromyalgia-related pain and other symptoms. Methods 573 patients with fibromyalgia according to 1990 American College of Rheumatology criteria were enrolled at 108 centres in eight countries. Subjects were randomly assigned to placebo, SXB 4.5 g/night or SXB 6 g/night. The primary efficacy endpoint was the proportion of subjects with ≥30% reduction in pain visual analogue scale from baseline to treatment end. Other efficacy assessments included function, sleep quality, effect of sleep on function, fatigue, tenderness, health-related quality of life and subject's impression of change in overall wellbeing. Results Significant improvements in pain, sleep and other symptoms associated with fibromyalgia were seen in SXB treated subjects compared with placebo. The proportion of subjects with ≥30% pain reduction was 42.0% for SXB4.5 g/night (p=0.002) and 51.4% for SXB6 g/night (p<0.001) versus 26.8% for placebo. Quality of sleep (Jenkins sleep scale) improved by 20% for SXB4.5 g/night (p≤0.001) and 25% for SXB6 g/night (p≤0.001) versus 0.5% for placebo. Adverse events with an incidence ≥5% and twice placebo were nausea, dizziness, vomiting, insomnia, anxiety, somnolence, fatigue, muscle spasms and peripheral oedema. Conclusion These results, combined with findings from previous phase 2 and 3 studies, provide supportive evidence that SXB therapy affordsimportant benefits across multiple symptoms in subjects with fibromyalgia. PMID:22294641

  6. Fasa Registry on Acute Myocardial Infarction (FaRMI): Feasibility Study and Pilot Phase Results

    PubMed Central

    Askari, Alireza; Zakeri, Habib; Farjam, Mojtaba; Dehghan, Azizallah; Zendehdel, Kazem

    2016-01-01

    Background Myocardial infarction (MI) is the leading cause of death in Iran. Every attempt to improve treatment patterns and patient outcomes needs a surveillance system to both consider the efficacy and safety measures. Fasa Registry on Myocardial Infarction (FaRMI) is the first population-based registry for acute MI in Iran targeted to provide meticulous description of patients’ characteristics, to explore the management patterns of these patients, to discover the degree of adherence to the practice guidelines, and to investigate the determinants of poor in-hospital and later outcomes. Methods A diagnosis of acute MI (type I, II and III) was made upon the accepted criteria by the attending cardiologists and types IV and V MI were excluded. Two registrar nurses gathered data on demographics, place of residence and ethnicity, past medical history, risk factors, and the clinical course. Management patterns in the pre-hospital setting, during the hospital stay and at the discharge time were recorded. Routine laboratory results and cardiac biomarkers on three consecutive days were registered. Results pilot phase included the first 95 patients, 63.5% of whom were men and 31.5% were women. With a mean age of 62.89±13.75 years among participants, the rate of premature MI was 31.8%. ST segment elevation MI accounted for 68.2% cases and inferior wall was the most prevalent region involved followed by anterior and posterior walls. Discussion Obtained data on the characteristics of patients suffering an MI event revealed the major determinants of delay in initiation of therapies and contributors of poor outcome. Completeness of data was guaranteed upon involvement of multiple checkpoints and data quality was secured by means of automatic validation processes in addition to weekly physicians’ roundups. Conclusion Execution of FaRMI in the form presented is feasible and it will build up a comprehensive population-based registry for MI in the region. PMID:27907128

  7. Stereotactic Body Radiotherapy for Localized Prostate Cancer: Interim Results of a Prospective Phase II Clinical Trial

    SciTech Connect

    King, Christopher R. Brooks, James D.; Gill, Harcharan; Pawlicki, Todd; Cotrutz, Cristian; Presti, Joseph C.

    2009-03-15

    Purpose: The radiobiology of prostate cancer favors a hypofractionated dose regimen. We report results of a prospective Phase II clinical trial of stereotactic body radiotherapy (SBRT) for localized prostate cancer. Methods and Materials: Forty-one low-risk prostate cancer patients with 6 months' minimum follow-up received 36.25 Gy in five fractions of 7.25 Gy with image-guided SBRT alone using the CyberKnife. The early (<3 months) and late (>6 months) urinary and rectal toxicities were assessed using validated quality of life questionnaires (International Prostate Symptom Score, Expanded Prostate Cancer Index Composite) and the Radiation Therapy Oncology Group (RTOG) toxicity criteria. Patterns of prostate-specific antigen (PSA) response are analyzed. Results: The median follow-up was 33 months. There were no RTOG Grade 4 acute or late rectal/urinary complications. There were 2 patients with RTOG Grade 3 late urinary toxicity and none with RTOG Grade 3 rectal complications. A reduced rate of severe rectal toxicities was observed with every-other-day vs. 5 consecutive days treatment regimen (0% vs. 38%, p = 0.0035). A benign PSA bounce (median, 0.4 ng/mL) was observed in 12 patients (29%) occurring at 18 months (median) after treatment. At last follow-up, no patient has had a PSA failure regardless of biochemical failure definition. Of 32 patients with 12 months minimum follow-up, 25 patients (78%) achieved a PSA nadir {<=}0.4 ng/mL. A PSA decline to progressively lower nadirs up to 3 years after treatment was observed. Conclusions: The early and late toxicity profile and PSA response for prostate SBRT are highly encouraging. Continued accrual and follow-up will be necessary to confirm durable biochemical control rates and low toxicity profiles.

  8. New Cyclic Voltammetry Method for Examining Phase Transitions on Electrodes: Simulated Results

    NASA Astrophysics Data System (ADS)

    Abou Hamad, Ibrahim; Robb, Daniel; Rikvold, Per Arne

    2007-03-01

    We propose a new experimental technique for cyclic voltammetry, based on the first-order reversal curve (FORC) method for analysis of systems undergoing hysteresis. The advantages of this technique are demonstrated by applying it to dynamical models of electrochemical adsorption. The method can not only differentiate between discontinuous and continuous phase transitions, but can also quite accurately recover equilibrium behavior from dynamic analysis of systems with a continuous phase transition. The FORC diagram for a discontinuous phase transition is characterized by a negative (unstable) region separating two positive (stable) regions, while such a negative region does not exist for continuous phase transitions. Experimental data for Electrochemical FORC (EC-FORC) analysis could easily be obtained by simple reprogramming of a potentiostat designed for conventional cyclic-voltammetry experiments.I. Abou Hamad, D.T. Robb, P.A. Rikvold, J. Electroanal. Chem., in press.

  9. Interaction-driven phases in a Dirac semimetal: exact diagonalization results.

    PubMed

    Guo, Huaiming; Jia, Yongfei

    2014-11-26

    The interaction-driven phases in the Dirac semimetal (SM) of the π-flux model on the square lattice are studied with nearest-(NN), next-nearest-(NNN) and next-next-nearest-neighbor (NNNN) interactions using the exact diagonalization method. We find that the NN interaction drives a phase transition from the SM phase to a charge density wave insulator. In the presence of the NNN interaction, the system becomes an anisotropic SM for small interactions and an insulator with the stripe order for large ones. The NNNN interaction drives the Dirac SM to a dimmerized insulator. The interplay of the NNN and NNNN interactions is also studied. We find that the NNNN interaction firstly eliminates the effect of the NNN interaction and then develops its favorable order. In the calculations, the signature of the interaction-driven quantum anomalous Hall phase is not found.

  10. New Results in Two-Phase Pressure Drop Calculations at Reduced Gravity Conditions

    NASA Astrophysics Data System (ADS)

    Braisted, Jon; Kurwitz, Cable; Best, Frederick

    2004-02-01

    The mass, power, and volume energy savings of two-phase systems for future spacecraft creates many advantages over current single-phase systems. Current models of two-phase phenomena such as pressure drop, void fraction, and flow regime prediction are still not well defined for space applications. Commercially available two-phase modeling software has been developed for a large range of acceleration fields including reduced-gravity conditions. Recently, a two-phase experiment has been flown to expand the two-phase database. A model of the experiment was created in the software to determine how well the software could predict the pressure drop observed in the experiment. Of the simulations conducted, the computer model shows good agreement of the pressure drop in the experiment to within 30%. However, the software does begin to over-predict pressure drop in certain regions of a flow regime map indicating that some models used in the software package for reduced-gravity modeling need improvement.

  11. Structure of the Vibrio cholerae Type IVb Pilus and stability comparison with the Neisseria gonorrhoeae type IVa pilus.

    PubMed

    Li, Juliana; Egelman, Edward H; Craig, Lisa

    2012-04-20

    Type IV pili are multifunctional filaments displayed on many bacterial pathogens. Members of the Type IVa pilus subclass are found on a diverse group of human pathogens, whereas Type IVb pili are found almost exclusively on enteric bacteria. The Type IVa and IVb subclasses are distinguished by differences in the pilin subunits, including the fold of the globular domain. To understand the implications of the distinct pilin folds, we compared the stabilities of pilin subunits and pilus filaments for the Type IVa GC pilus from Neisseria gonorrhoeae and the Type IVb toxin-coregulated pilus (TCP) from Vibrio cholerae. We show that while recombinant TCP pilin is more stable than GC pilin, the GC pili are more resistant to proteolysis, heat and chemical denaturation than TCP, remaining intact in 8 M urea. To understand these differences, we determined the TCP structure by electron microscopy and three-dimensional image reconstruction. TCP have an architecture similar to that of GC pili, with subunits arranged in a right-handed 1-start helix and related by an 8.4-Å axial rise and a 96.8° azimuthal rotation. However, the TCP subunits are not as tightly packed as GC pilins, and the distinct Type IVb pilin fold exposes a segment of the α-helical core of TCP. Hydrophobic interactions dominate for both pilus subtypes, but base stacking by aromatic residues conserved among the Type IVa pilins may contribute to GC pilus stability. The extraordinary stability of GC pili may represent an adaptation of the Type IVa pili to harsh environments and the need to retract against external forces. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. MRI morphometric characterisation of the paediatric cervical spine and spinal cord in children with MPS IVA (Morquio-Brailsford syndrome).

    PubMed

    Solanki, Guirish A; Lo, William B; Hendriksz, Christian J

    2013-03-01

    Nearly all children with MPS IVA develop skeletal deformities affecting the spine. At the atlanto-axial spine, odontoid hypoplasia occurs. GAG deposition around the dens, leads to peri-odontoid infiltration. Transverse/alar ligament incompetence causes instability. Atlanto-axial instability is associated with cord compression and myelopathy, leading to major morbidity and mortality. Intervention is often required. Does the presence of widened bullet shaped vertebra in platyspondily encroach on the spinal canal and cause spinal stenosis in MPS IVA? So far, there have been no standardised morphometric measurements of the paediatric MPS IVA cervical spine to evaluate whether there is pre-existing spinal stenosis predisposing to compressive myelopathy or whether this is purely an acquired process secondary to instability and compression. This study provides the first radiological quantitative analysis of the cervical spine and spinal cord in a series of affected children. MRI morphometry indicates that the MPS IVA spine is narrower at C1-2 level giving an inverted funnel shape. There is no evidence of a reduction in the Torg ratio (canal-body ratio) in the cervical spine. The spinal canal does not exceed 11 mm at any level, significantly smaller than normal historical cohorts (14 mm). The sagittal diameter and axial surface area of both spinal canal and cord are reduced. C1-2 level cord compression was evident in the canal-cord ratio but the Torg ratio was not predictive of cord compression. In MPS IVA the reduction in the space available for the cord (SAC) is multifactorial rather than due to congenital spinal stenosis.

  13. PilN binding modulates the structure and binding partners of the Pseudomonas aeruginosa type IVa pilus protein PilM

    DOE PAGES

    McCallum, Matthew; Tammam, Stephanie; Little, Dustin J.; ...

    2016-03-28

    Pseudomonas aeruginosa is an opportunistic bacterial pathogen that expresses type IVa pili. The pilus assembly system, which promotes surface-associated twitching motility and virulence, is composed of inner and outer membrane subcomplexes, connected by an alignment subcomplex composed of PilMNOP. PilM binds to the N terminus of PilN, and we hypothesize that this interaction causes functionally significant structural changes in PilM. To characterize this interaction, we determined the crystal structures of PilM and a PilM chimera where PilM was fused to the first 12 residues of PilN (PilM·PilN(1–12)). Structural analysis, multiangle light scattering coupled with size exclusion chromatography, and bacterial two-hybridmore » data revealed that PilM forms dimers mediated by the binding of a novel conserved motif in the N terminus of PilM, and binding PilN abrogates this binding interface, resulting in PilM monomerization. Structural comparison of PilM with PilM·PilN(1–12) revealed that upon PilN binding, there is a large domain closure in PilM that alters its ATP binding site. Using biolayer interferometry, we found that the association rate of PilN with PilM is higher in the presence of ATP compared with ADP. Bacterial two-hybrid data suggested the connectivity of the cytoplasmic and inner membrane components of the type IVa pilus machinery in P. aeruginosa, with PilM binding to PilB, PilT, and PilC in addition to PilN. Pull-down experiments demonstrated direct interactions of PilM with PilB and PilT. As a result, we propose a working model in which dynamic binding of PilN facilitates functionally relevant structural changes in PilM.« less

  14. PilN binding modulates the structure and binding partners of the Pseudomonas aeruginosa type IVa pilus protein PilM

    SciTech Connect

    McCallum, Matthew; Tammam, Stephanie; Little, Dustin J.; Robinson, Howard; Koo, Jason; Shah, Megha; Calmettes, Charles; Moraes, Trevor F.; Burrows, Lori L.; Howell, P. Lynne

    2016-03-28

    Pseudomonas aeruginosa is an opportunistic bacterial pathogen that expresses type IVa pili. The pilus assembly system, which promotes surface-associated twitching motility and virulence, is composed of inner and outer membrane subcomplexes, connected by an alignment subcomplex composed of PilMNOP. PilM binds to the N terminus of PilN, and we hypothesize that this interaction causes functionally significant structural changes in PilM. To characterize this interaction, we determined the crystal structures of PilM and a PilM chimera where PilM was fused to the first 12 residues of PilN (PilM·PilN(1–12)). Structural analysis, multiangle light scattering coupled with size exclusion chromatography, and bacterial two-hybrid data revealed that PilM forms dimers mediated by the binding of a novel conserved motif in the N terminus of PilM, and binding PilN abrogates this binding interface, resulting in PilM monomerization. Structural comparison of PilM with PilM·PilN(1–12) revealed that upon PilN binding, there is a large domain closure in PilM that alters its ATP binding site. Using biolayer interferometry, we found that the association rate of PilN with PilM is higher in the presence of ATP compared with ADP. Bacterial two-hybrid data suggested the connectivity of the cytoplasmic and inner membrane components of the type IVa pilus machinery in P. aeruginosa, with PilM binding to PilB, PilT, and PilC in addition to PilN. Pull-down experiments demonstrated direct interactions of PilM with PilB and PilT. As a result, we propose a working model in which dynamic binding of PilN facilitates functionally relevant structural changes in PilM.

  15. Stable water isotope simulation by current land-surface schemes:Results of IPILPS phase 1

    SciTech Connect

    Henderson-Sellers, A.; Fischer, M.; Aleinov, I.; McGuffie, K.; Riley, W.J.; Schmidt, G.A.; Sturm, K.; Yoshimura, K.; Irannejad, P.

    2005-10-31

    Phase 1 of isotopes in the Project for Intercomparison of Land-surface Parameterization Schemes (iPILPS) compares the simulation of two stable water isotopologues ({sup 1}H{sub 2} {sup 18}O and {sup 1}H{sup 2}H{sup 16}O) at the land-atmosphere interface. The simulations are off-line, with forcing from an isotopically enabled regional model for three locations selected to offer contrasting climates and ecotypes: an evergreen tropical forest, a sclerophyll eucalypt forest and a mixed deciduous wood. Here we report on the experimental framework, the quality control undertaken on the simulation results and the method of intercomparisons employed. The small number of available isotopically-enabled land-surface schemes (ILSSs) limits the drawing of strong conclusions but, despite this, there is shown to be benefit in undertaking this type of isotopic intercomparison. Although validation of isotopic simulations at the land surface must await more, and much more complete, observational campaigns, we find that the empirically-based Craig-Gordon parameterization (of isotopic fractionation during evaporation) gives adequately realistic isotopic simulations when incorporated in a wide range of land-surface codes. By introducing two new tools for understanding isotopic variability from the land surface, the Isotope Transfer Function and the iPILPS plot, we show that different hydrological parameterizations cause very different isotopic responses. We show that ILSS-simulated isotopic equilibrium is independent of the total water and energy budget (with respect to both equilibration time and state), but interestingly the partitioning of available energy and water is a function of the models' complexity.

  16. Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study

    PubMed Central

    Ansell, Stephen M.; Armand, Philippe; Scott, Emma C.; Halwani, Ahmad; Gutierrez, Martin; Millenson, Michael M.; Cohen, Adam D.; Schuster, Stephen J.; Lebovic, Daniel; Dhodapkar, Madhav; Avigan, David; Chapuy, Bjoern; Ligon, Azra H.; Freeman, Gordon J.; Rodig, Scott J.; Cattry, Deepika; Zhu, Lili; Grosso, Joseph F.; Bradley Garelik, M. Brigid; Shipp, Margaret A.; Borrello, Ivan; Timmerman, John

    2016-01-01

    Purpose Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies. Methods In this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti–PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression. Results Eighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2. Objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks. Conclusion Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B- and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing. PMID:27269947

  17. Ipilimumab with Stereotactic Ablative Radiation Therapy: Phase I Results and Immunologic Correlates from Peripheral T Cells.

    PubMed

    Tang, Chad; Welsh, James W; de Groot, Patricia; Massarelli, Erminia; Chang, Joe Y; Hess, Kenneth R; Basu, Sreyashi; Curran, Michael A; Cabanillas, Maria E; Subbiah, Vivek; Fu, Siqing; Tsimberidou, Apostolia M; Karp, Daniel; Gomez, Daniel R; Diab, Adi; Komaki, Ritsuko; Heymach, John V; Sharma, Padmanee; Naing, Aung; Hong, David S

    2017-03-15

    Purpose: Little prospective data are available on clinical outcomes and immune correlates from combination radiation and immunotherapy. We conducted a phase I trial (NCT02239900) testing stereotactic ablative radiotherapy (SABR) with ipilimumab.Experimental Design: SABR was given either concurrently (1 day after the first dose) or sequentially (1 week after the second dose) with ipilimumab (3 mg/kg every 3 weeks for 4 doses) to five treatment groups: concurrent 50 Gy (in 4 fractions) to liver; sequential 50 Gy (in 4 fractions) to liver; concurrent 50 Gy (in 4 fractions) to lung; sequential 50 Gy (in 4 fractions) to lung; and sequential 60 Gy (in 10 fractions) to lung or liver. MTD was determined with a 3 + 3 dose de-escalation design. Immune marker expression was assessed by flow cytometry.Results: Among 35 patients who initiated ipilimumab, 2 experienced dose-limiting toxicity and 12 (34%) grade 3 toxicity. Response outside the radiation field was assessable in 31 patients. Three patients (10%) exhibited partial response and 7 (23%) experienced clinical benefit (defined as partial response or stable disease lasting ≥6 months). Clinical benefit was associated with increases in peripheral CD8(+) T cells, CD8(+)/CD4(+) T-cell ratio, and proportion of CD8(+) T cells expressing 4-1BB and PD1. Liver (vs. lung) irradiation produced greater T-cell activation, reflected as increases in the proportions of peripheral T cells expressing ICOS, GITR, and 4-1BB.Conclusions: Combining SABR and ipilimumab was safe with signs of efficacy, peripheral T-cell markers may predict clinical benefit, and systemic immune activation was greater after liver irradiation. Clin Cancer Res; 23(6); 1388-96. ©2016 AACR.

  18. Treatment of Geographic Atrophy With Subconjunctival Sirolimus: Results of a Phase I/II Clinical Trial

    PubMed Central

    Wong, Wai T.; Dresner, Samuel; Forooghian, Farzin; Glaser, Tanya; Doss, Lauren; Zhou, Mei; Cunningham, Denise; Shimel, Katherine; Harrington, Molly; Hammel, Keri; Cukras, Catherine A.; Ferris, Frederick L.; Chew, Emily Y.

    2013-01-01

    Purpose. To investigate the safety and effects of subconjunctival sirolimus, an mTOR inhibitor and immunosuppressive agent, for the treatment of geographic atrophy (GA). Methods. The study was a single-center, open-label phase II trial, enrolling 11 participants with bilateral GA; eight participants completed 24 months of follow-up. Sirolimus (440 μg) was administered every 3 months as a subconjunctival injection in only one randomly assigned eye in each participant for 24 months. Fellow eyes served as untreated controls. The primary efficacy outcome measure was the change in the total GA area at 24 months. Secondary outcomes included changes in visual acuity, macular sensitivity, central retinal thickness, and total drusen area. Results. The study drug was well tolerated with few symptoms and related adverse events. Study treatment in study eyes was not associated with structural or functional benefits relative to the control fellow eyes. At month 24, mean GA area increased by 54.5% and 39.7% in study and fellow eyes, respectively (P = 0.41), whereas mean visual acuity decreased by 21.0 letters and 3.0 letters in study and fellow eyes, respectively (P = 0.03). Substantial differences in mean changes in drusen area, central retinal thickness, and macular sensitivity were not detected for all analysis time points up to 24 months. Conclusions. Repeated subconjunctival sirolimus was well-tolerated in patients with GA, although no positive anatomic or functional effects were identified. Subconjunctival sirolimus may not be beneficial in the prevention of GA progression, and may potentially be associated with effects detrimental to visual acuity. (ClinicalTrials.gov number, NCT00766649.) PMID:23548622

  19. Anthropogenic Heat Flux Estimation from Space: Results of the second phase of the URBANFLUXES Project

    NASA Astrophysics Data System (ADS)

    Chrysoulakis, Nektarios; Marconcini, Mattia; Gastellu-Etchegorry, Jean-Philippe; Grimmond, Sue; Feigenwinter, Christian; Lindberg, Fredrik; Del Frate, Fabio; Klostermann, Judith; Mitraka, Zina; Esch, Thomas; Landier, Lucas; Gabey, Andy; Parlow, Eberhard; Olofson, Frans

    2017-04-01

    The H2020-Space project URBANFLUXES (URBan ANthrpogenic heat FLUX from Earth observation Satellites) investigates the potential of Copernicus Sentinels to retrieve anthropogenic heat flux, as a key component of the Urban Energy Budget (UEB). URBANFLUXES advances the current knowledge of the impacts of UEB fluxes on urban heat island and consequently on energy consumption in cities. In URBANFLUXES, the anthropogenic heat flux is estimated as a residual of UEB. Therefore, the rest UEB components, namely, the net all-wave radiation, the net change in heat storage and the turbulent sensible and latent heat fluxes are independently estimated from Earth Observation (EO), whereas the advection term is included in the error of the anthropogenic heat flux estimation from the UEB closure. The Discrete Anisotropic Radiative Transfer (DART) model is employed to improve the estimation of the net all-wave radiation balance, whereas the Element Surface Temperature Method (ESTM), adjusted to satellite observations is used to improve the estimation the estimation of the net change in heat storage. Furthermore the estimation of the turbulent sensible and latent heat fluxes is based on the Aerodynamic Resistance Method (ARM). Based on these outcomes, QF is estimated by regressing the sum of the turbulent heat fluxes versus the available energy. In-situ flux measurements are used to evaluate URBANFLUXES outcomes, whereas uncertainties are specified and analyzed. URBANFLUXES is expected to prepare the ground for further innovative exploitation of EO in scientific activities (climate variability studies at local and regional scales) and future and emerging applications (sustainable urban planning, mitigation technologies) to benefit climate change mitigation/adaptation. This study presents the results of the second phase of the project and detailed information on URBANFLUXES is available at: http://urbanfluxes.eu

  20. Anthropogenic Heat Flux Estimation from Space: Results of the first phase of the URBANFLUXES Project

    NASA Astrophysics Data System (ADS)

    Chrysoulakis, N.; Marconcini, M.; Gastellu-Etchegorry, J. P.; Grimmond, S. B.; Feigenwinter, C.; Lindberg, F.; Del Frate, F.; Klostermann, J.; Mitraka, Z.; Esch, T.; Landier, L.; Gabey, A. M.; Parlow, E.; Olofson, F.

    2016-12-01

    The H2020-Space project URBANFLUXES (URBan ANthrpogenic heat FLUX from Earth observation Satellites) investigates the potential of Copernicus Sentinels to retrieve anthropogenic heat flux, as a key component of the Urban Energy Budget (UEB). URBANFLUXES advances the current knowledge of the impacts of UEB fluxes on urban heat island and consequently on energy consumption in cities. In URBANFLUXES, the anthropogenic heat flux is estimated as a residual of UEB. Therefore, the rest UEB components, namely, the net all-wave radiation, the net change in heat storage and the turbulent sensible and latent heat fluxes are independently estimated from Earth Observation (EO), whereas the advection term is included in the error of the anthropogenic heat flux estimation from the UEB closure. The Discrete Anisotropic Radiative Transfer (DART) model is employed to improve the estimation of the net all-wave radiation balance, whereas the Element Surface Temperature Method (ESTM), adjusted to satellite observations is used to improve the estimation the estimation of the net change in heat storage. Furthermore the estimation of the turbulent sensible and latent heat fluxes is based on the Aerodynamic Resistance Method (ARM). Based on these outcomes, QF is estimated by regressing the sum of the turbulent heat fluxes versus the available energy. In-situ flux measurements are used to evaluate URBANFLUXES outcomes, whereas uncertainties are specified and analyzed. URBANFLUXES is expected to prepare the ground for further innovative exploitation of EO in scientific activities (climate variability studies at local and regional scales) and future and emerging applications (sustainable urban planning, mitigation technologies) to benefit climate change mitigation/adaptation. This study presents the results of the first phase of the project and detailed information on URBANFLUXES is available at: http://urbanfluxes.eu

  1. Optimized tracking of RF carriers with phase noise, including Pioneer 10 results

    NASA Technical Reports Server (NTRS)

    Vilnrotter, V. A.; Hurd, W. J.; Brown, D. H.

    1987-01-01

    The ability to track very weak signals from distant spacecraft is limited by the phase instabilities of the received signal and of the local oscillator employed by the receiver. These instabilities ultimately limit the minimum loop bandwidth that can be used in a phase-coherent receiver, and hence limit the ratio of received carrier power to noise spectral density which can be tracked phase coherently. A method is presented for near real time estimation of the received carrier phase and additive noise spectrum, and optimization of the phase locked loop bandwidth. The method was used with the breadboard Deep Space Network (DSN) Advanced Receiver to optimize tracking of very weak signals from the Pioneer 10 spacecraft, which is now more distant that the edge of the solar system. Tracking with bandwidths of 0.1 Hz to 1.0 Hz reduces tracking signal threshold and increases carrier loop signal to noise ratio (SNR) by 5 dB to 15 dB compared to the 3 Hz bandwidth of the receivers now used operationally in the DSN. This will enable the DSN to track Pioneer 10 until its power sources fails near the end of the century.

  2. Arctic Mixed-Phase Cloud Properties from AERI Lidar Observations: Algorithm and Results from SHEBA

    SciTech Connect

    Turner, David D.

    2005-04-01

    A new approach to retrieve microphysical properties from mixed-phase Arctic clouds is presented. This mixed-phase cloud property retrieval algorithm (MIXCRA) retrieves cloud optical depth, ice fraction, and the effective radius of the water and ice particles from ground-based, high-resolution infrared radiance and lidar cloud boundary observations. The theoretical basis for this technique is that the absorption coefficient of ice is greater than that of liquid water from 10 to 13 μm, whereas liquid water is more absorbing than ice from 16 to 25 μm. MIXCRA retrievals are only valid for optically thin (τvisible < 6) single-layer clouds when the precipitable water vapor is less than 1 cm. MIXCRA was applied to the Atmospheric Emitted Radiance Interferometer (AERI) data that were collected during the Surface Heat Budget of the Arctic Ocean (SHEBA) experiment from November 1997 to May 1998, where 63% of all of the cloudy scenes above the SHEBA site met this specification. The retrieval determined that approximately 48% of these clouds were mixed phase and that a significant number of clouds (during all 7 months) contained liquid water, even for cloud temperatures as low as 240 K. The retrieved distributions of effective radii for water and ice particles in single-phase clouds are shown to be different than the effective radii in mixed-phase clouds.

  3. First imaging results from Apertif, a phased-array feed for WSRT

    NASA Astrophysics Data System (ADS)

    Adams, Elizabeth A.; Adebahr, Björn; de Blok, Willem J. G.; Hess, Kelley M.; Hut, Boudewijn; Lucero, Danielle M.; Maccagni, Filippo; Morganti, Raffaella; Oosterloo, Tom; Staveley-Smith, Lister; van der Hulst, Thijs; Verheijen, Marc; Verstappen, Joris

    2017-01-01

    Apertif is a phased-array feed for the Westerbork Synthesis Radio Telescope (WSRT), increasing the field of view of the telescope by a factor of twenty-five. In 2017, three legacy surveys will commence: a shallow imaging survey, a medium-deep imaging survey, and a pulsars and fast transients survey. The medium-deep imaging survey will include coverage of the northern Herschel Atlas field, the CVn region, HetDex, and the Perseus-Pisces supercluster. The shallow imaging survey increases overlap with HetDex, has expanded coverage of the Perseus-Pisces supercluster, and includes part of the Zone of Avoidance. Both imaging surveys are coordinating with MaNGA and will have WEAVE follow-up. The imaging surveys will be done in full polarization over the frequency range 1130-1430 MHz, which corresponds to redshifts of z=0-0.256 for neutral hydrogen (HI). The spectral resolution is 12.2 kHz, or an HI velocity resolution of 2.6 km/s at z=0 and 3.2 km/s at z=0.256. The full resolution images will have a beam size of 15"x15"/sin(declination), and tapered data products (i.e., 30" resolution images) will also be available. The shallow survey will cover ~3500 square degrees with a four-sigma HI imaging sensitivity of 2.5x10^20 atoms cm^-2 (20 km/s linewidth) at the highest resolution and a continuum sensitivity of 15 uJy/beam (11 uJy/beam for polarization data). The current plan calls for the medium deep survey to cover 450 square degrees and provide an HI imaging sensitivity of 1.0x10^20 atoms cm^-2 at the highest resolution and a continuum sensitivity of 6 uJy/beam, close to the confusion limit (4 uJy/beam for polarization data, not confusion limited). Up-to-date information on Apertif and the planned surveys can be found at: http://www.apertif.nl.Commissioning of the Apertif instrument is currently underway. Here we present first results from the image commissioning, including the detection of HI absorption plus continuum and HI imaging. These results highlight the data quality

  4. Safety with Ocrelizumab in Rheumatoid Arthritis: Results from the Ocrelizumab Phase III Program

    PubMed Central

    Emery, Paul; Rigby, William; Tak, Paul P.; Dörner, Thomas; Olech, Ewa; Martin, Carmen; Millar, Laurie; Travers, Helen; Fisheleva, Elena

    2014-01-01

    Objective The objective was to determine the safety of ocrelizumab (OCR) in patients with rheumatoid arthritis (RA). Methods This was an analysis of the double-blind, placebo-controlled periods and long-term follow-up of 4 OCR phase III trials in RA (SCRIPT, STAGE, FILM and FEATURE). Safety data per study and the results of a meta-analysis of serious infectious events (SIEs) are presented. Results Overall, 868 patients received placebo, 1064 patients OCR 200 mg×2 (or 400 mg×1) (OCR200), and 827 patients OCR 500 mg×2 (OCR500) plus background methotrexate (MTX) at baseline and 24 weeks. During the double-blind, placebo-controlled periods, the incidence of adverse events and serious adverse events was comparable between the OCR+MTX and placebo +MTX groups. Infusion-related reactions were more common with OCR+MTX and decreased in frequency with subsequent infusions. Serious infusion-related reactions were rare (0.1%). Serious infections occurred more frequently with OCR500+MTX. In the meta-analysis, a statistically significant difference from placebo +MTX in incidence of SIEs per 100 patient-years of 2.4 (95% CI, 0.3–4.5) was observed with OCR500+MTX, but not with OCR200+MTX (0.6; 95% CI, −1.3 to 2.4). Patients recruited in Asia exhibited a higher risk of serious infections (hazard ratio, 1.78; 95% CI, 1.03–3.06). The incidence of human anti-human antibodies was <5%. Long-term follow-up indicated no differences in malignancy rates between the treatment groups. There was no apparent difference in time to B-cell repletion between the OCR dose groups. Conclusions In placebo-controlled clinical trials of RA, OCR500+MTX was associated with a higher risk of serious infections compared with placebo +MTX. The safety profile of OCR 200+MTX was comparable with placebo+MTX. Trial Registration STAGE Clinical Trials.gov NCT00406419 SCRIPT Clinical Trials.gov NCT00476996 FILM Clinical Trials.gov NCT00485589 FEATURE Clinical Trials.gov NCT00673920 PMID:24498318

  5. Development and application of quantitative detection method for viral hemorrhagic septicemia virus (VHSV) genogroup IVa.

    PubMed

    Kim, Jong-Oh; Kim, Wi-Sik; Kim, Si-Woo; Han, Hyun-Ja; Kim, Jin Woo; Park, Myoung Ae; Oh, Myung-Joo

    2014-05-23

    Viral hemorrhagic septicemia virus (VHSV) is a problematic pathogen in olive flounder (Paralichthys olivaceus) aquaculture farms in Korea. Thus, it is necessary to develop a rapid and accurate diagnostic method to detect this virus. We developed a quantitative RT-PCR (qRT-PCR) method based on the nucleocapsid (N) gene sequence of Korean VHSV isolate (Genogroup IVa). The slope and R² values of the primer set developed in this study were -0.2928 (96% efficiency) and 0.9979, respectively. Its comparison with viral infectivity calculated by traditional quantifying method (TCID₅₀) showed a similar pattern of kinetic changes in vitro and in vivo. The qRT-PCR method reduced detection time compared to that of TCID₅₀, making it a very useful tool for VHSV diagnosis.

  6. Seasat wind and wave observations of northeast Pacific hurricane Iva, August 13, 1978

    NASA Technical Reports Server (NTRS)

    Gonzalez, F. I.; Thompson, T. W.; Brown, W. E., Jr.; Weissman, D. E.

    1982-01-01

    The paper examines Seasat wind and wave observations collected in the eye of hurricane Iva on August 13, 1978 in the northeast Pacific. A maximum wind speed of 25-30 m/s is observed, along with a banana-shape high-wind-speed distribution. Two-dimensional Fourier transforms of selected SAR scenes show a dominant wavefield characterized by wavelengths of 166-211 m, with a fanlike distribution of propagation directions. A simple geometric model is proposed to explain the dominant wave field in terms of prior storm intensity and location, which is combined with the Ross parametric hurricane wave model and Seasat wind and wave data to estimate a value of 43 km for the effective radial distance from the storm center to the region of maximum winds.

  7. Transparent conductivity modulation of ZnO by group-IVA doping

    NASA Astrophysics Data System (ADS)

    Liu, J.; Fan, X. F.; Sun, C. Q.; Zhu, W.

    2016-04-01

    We examined the effect of group-IVA doping on the electronic structure and transmittance of ZnO using first-principle calculations. All these doped ZnO materials are found to perform n-type conductive behavior. Si-doped ZnO and Pb-doped ZnO are found to have larger optical band gap than those of Ge-doped ZnO and Sn-doped ZnO. The transmittance of Si-doped ZnO is found to be high in both UV and visible region. The enhancement of UV region transmittance can be attributed to the enhanced optical band gap, while the reduction of visible region transmittance is due to the intraband optical transition.

  8. Seasat wind and wave observations of northeast Pacific hurricane Iva, August 13, 1978

    NASA Technical Reports Server (NTRS)

    Gonzalez, F. I.; Thompson, T. W.; Brown, W. E., Jr.; Weissman, D. E.

    1982-01-01

    The paper examines Seasat wind and wave observations collected in the eye of hurricane Iva on August 13, 1978 in the northeast Pacific. A maximum wind speed of 25-30 m/s is observed, along with a banana-shape high-wind-speed distribution. Two-dimensional Fourier transforms of selected SAR scenes show a dominant wavefield characterized by wavelengths of 166-211 m, with a fanlike distribution of propagation directions. A simple geometric model is proposed to explain the dominant wave field in terms of prior storm intensity and location, which is combined with the Ross parametric hurricane wave model and Seasat wind and wave data to estimate a value of 43 km for the effective radial distance from the storm center to the region of maximum winds.

  9. Development and Application of Quantitative Detection Method for Viral Hemorrhagic Septicemia Virus (VHSV) Genogroup IVa

    PubMed Central

    Kim, Jong-Oh; Kim, Wi-Sik; Kim, Si-Woo; Han, Hyun-Ja; Kim, Jin Woo; Park, Myoung Ae; Oh, Myung-Joo

    2014-01-01

    Viral hemorrhagic septicemia virus (VHSV) is a problematic pathogen in olive flounder (Paralichthys olivaceus) aquaculture farms in Korea. Thus, it is necessary to develop a rapid and accurate diagnostic method to detect this virus. We developed a quantitative RT-PCR (qRT-PCR) method based on the nucleocapsid (N) gene sequence of Korean VHSV isolate (Genogroup IVa). The slope and R2 values of the primer set developed in this study were −0.2928 (96% efficiency) and 0.9979, respectively. Its comparison with viral infectivity calculated by traditional quantifying method (TCID50) showed a similar pattern of kinetic changes in vitro and in vivo. The qRT-PCR method reduced detection time compared to that of TCID50, making it a very useful tool for VHSV diagnosis. PMID:24859343

  10. INDEPENDENT TECHNICAL REVIEW OF THE C-400 INTERIM REMEDIAL PROJECT PHASE I RESULTS, PADUCAH, KENTUCKY

    SciTech Connect

    Looney, B.; Rossabi, J.; Stewart,L.; Richards, W.

    2010-10-29

    The groundwater and soil in the vicinity of the C-400 Building at the Paducah Gaseous Diffusion Plant (PGDP), is contaminated with substantial quantities of industrial solvents, primarily trichoroethene (TCE). This solvent 'source' is recognized as a significant challenge and an important remediation target in the overall environmental cleanup strategy for PGDP. Thus, the cleanup of the C-400 TCE Source is a principal focus for the Department of Energy (DOE) and its contractors, and for PGDP regulators and stakeholders. Using a formal investigation, feasibility study and decision process, Electrical Resistance Heating (ERH) was selected for the treatment of the soil and groundwater in the vicinity of C-400. ERH was selected as an interim action to remove 'a significant portion of the contaminant mass of TCE at the C-400 Cleaning Building area through treatment' with the longer term goal of reducing 'the period the TCE concentration in groundwater remains above its Maximum Contaminant Level (MCL).' ERH is a thermal treatment that enhances the removal of TCE and related solvents from soil and groundwater. The heterogeneous conditions at PGDP, particularly the high permeability regional gravel aquifer (RGA), are challenging to ERH. Thus, a phased approach is being followed to implement this relatively expensive and complex remediation technology. Conceptually, the phased approach encourages safety and efficiency by providing a 'lessons learned' process and allowing appropriate adjustments to be identified and implemented prior to follow-on phase(s) of treatment. More specifically, early deployment targeted portions of the challenging RGA treatment zone with relatively little contamination reducing the risk of adverse collateral impacts from underperformance in terms of heating and capture. Because of the importance and scope of the C-400 TCE source remediation activities, DOE chartered an Independent Technical Review (ITR) in 2007 to assess the C-400 ERH plans prior

  11. Calculation of Impedance from Multibunch Synchronous Phases: Theory and Experimental Results

    SciTech Connect

    Prabhakar, Shyam

    1998-10-20

    A novel beam-based method for measuring the longitudinal impedance spectrum is demonstrated using experimental data from the PEP-II High Energy Ring (HER). The method uses a digital longitudinal feedback system from which the charge and synchronous phase are measured for every bucket. Calculation of the transfer function from fill shape to synchronous phase yields the impedance seen by the beam at revolution harmonics. The experimentally-derived longitudinal impedance function and lab measurements of the impedance of parked RF cavities are compared to suggest a mechanism for the occasional instability of low-order coupled bunch modes observed in the HER during commissioning in October 1997.

  12. The Two-Phase Flow Separator Experiment Breadboard Model: Reduced Gravity Aircraft Results

    NASA Technical Reports Server (NTRS)

    Rame, E; Sharp, L. M.; Chahine, G.; Kamotani, Y.; Gotti, D.; Owens, J.; Gilkey, K.; Pham, N.

    2015-01-01

    Life support systems in space depend on the ability to effectively separate gas from liquid. Passive cyclonic phase separators use the centripetal acceleration of a rotating gas-liquid mixture to carry out phase separation. The gas migrates to the center, while gas-free liquid may be withdrawn from one of the end plates. We have designed, constructed and tested a breadboard that accommodates the test sections of two independent principal investigators and satisfies their respective requirements, including flow rates, pressure and video diagnostics. The breadboard was flown in the NASA low-gravity airplane in order to test the system performance and design under reduced gravity conditions.

  13. Magmatic activity on the IVA parent body: Evidence from silicate-bearing iron meteorites

    NASA Astrophysics Data System (ADS)

    Ulff-Møller, Finn; Rasmussen, Kaare L.; Prinz, Martin; Palme, Herbert; Spettel, Bernhardt; Kallemeyn, Gregory W.

    1995-11-01

    Four of the magmatic IVA iron meteorites contain tridymite or clinobronzite-orthobronzitetridymite which are quite unlike silicate assemblages in other iron meteorites. The textures, the bulk chemistry, and the zoning preserved in the pyroxenes strongly suggest that they are igneous cumulates. The pyroxenes have extremely low Fe/Mn-ratios (less than 20) and low contents of REEs and other incompatible elements. These cumulates crystallized from magmas of unusual composition, with some similarity to terrestrial boninites, at the protobronzite-tfdymite cotectic in the olivine-plagioclase-silica system. A liquidus temperature in the range 1400-1350°C was inferred for the Steinbach meteorite from the estimated distribution coefficient for Cr in pyroxene ( DCrsolid/liquid ˜ 0.66). The low levels of incompatible elements show that less than 1% of the residual liquid was trapped in the cumulates. During cooling at subsolidus temperatures, most of the protobronzite transformed to orthobronzite and the rest inverted to a fine inter-growth of clino- and orthobronzite. In addition, the igneous zoning of Ca, Fe, Mg, and Mn was modified by diffusion, whereas Ti, Al, and Cr were not or only slightly affected. The silica-saturated magmas could not have evolved in an olivine-rich mantle. We assume that the magmas became incorporated in the metal core, possibly due to solidification shrinkage of the metal. We propose that the IVA parent magmas were formed by high degrees of partial melting (>40%) of a chondritic precursor along the olivine-pyroxene peritectic reaction curve in the olivine-plagioclase-silica system at low pressures. The precursor may have been depleted in incompatible elements by a preceding melting episode. The partial melts were then separated from the olivine residue and subsequently reduced to account for the low Fe/Mn- ratios and the unusually high Si content.

  14. Acute hypoglycemic, hypocholesterolemic and hypotriglyceridemic effects of continuous intravenous infusion of a lyophilised aqueous extract of Ajuga iva L. Schreber whole plant in streptozotocin-induced diabetic rats.

    PubMed

    El-Hilaly, Jaouad; Tahraoui, Adil; Israili, Zafar H; Lyoussi, Badiâa

    2007-10-01

    The hypoglycemic and hypolipidemic effect of continuous intravenous infusion of a lyophilised aqueous extract of the whole plant Ajuga iva (L.) Schreber (Labiatae) (AI-extract) was investigated in anesthetized normal and streptozotocin (STZ)-induced diabetic rats. The AI-extract was administered to a group of rats by continuous intravenous infusion for 4 h at a dose of 4.2 microg/min/100 g body weight; another group was infused with taurine, the reference compound, at the same dose. In normal rats, AI-extract infusion had no effect on plasma glucose or triglycerides, but plasma cholesterol levels were significantly decreased (22%; P<0.05). However, taurine infusion produced significant hypoglycemic, hypocholesterolemic and hypotriglyceridemic effects (all changes, P<0.05). In STZ-diabetic rats, AI-extract infusion reduced plasma levels of glucose by 24 % (P<0.05), cholesterol by 35% (P<0.01) and triglycerides by 13% (P<0.05). Infusion with taurine produced a greater fall in plasma glucose (72%, P<0.01), cholesterol (54%; P<0.001) and triglyceride (24%; P<0.001) levels. Our results indicate that intravenously administered AI-extract exerts hypoglycemic and hypolipidemic effects in diabetic rats by mechanism(s) which appear to be similar to that of taurine, which involve insulin sensitization or an insulin-like effect. The identity and the exact mechanism(s) of action of the active component(s) of the AI-extract are not known. Ajuga iva appears to be a useful plant in the therapy of diabetes, a condition in which hyperglycemia and dyslipidemia coexist quite often.

  15. Segmental arterial mediolysis of varying phases affecting both the intra-abdominal and intracranial vertebral arteries: an autopsy case report.

    PubMed

    Ro, Ayako; Kageyama, Norimasa; Takatsu, Akihiro; Fukunaga, Tatsushige

    2010-01-01

    We report an autopsy case of segmental arterial mediolysis (SAM) of various phases occurring in both the intracranial vertebral artery (IVA) and intra-abdominal arteries. The patient was a 70-year-old male found dead in his house. The cause of death was massive intra-abdominal hemorrhage owing to a ruptured right gastroepiploic artery. Histopathological examination revealed that there was a broad arterial dissection as long as 20 cm in the right gastroepiploic artery associated with SAM in the injurious phase. In addition, SAM in the reparative phase was observed as organized arterial dissections in the left gastric artery. Furthermore, SAM in the reparative phase was detected as an arterial dissection in the right IVA undergoing an organizing process. These three lesions were considered to have developed at different times. SAM occurring in both the intra-abdominal and intracranial vertebral arteries is extremely rare. This coincidence may provide a clue to the relationship between SAM and spontaneous IVA dissection.

  16. REFINEMENT OF THE NEPHELINE DISCRIMINATOR: RESULTS OF A PHASE I STUDY

    SciTech Connect

    Fox, K; James Newell, J; Tommy Edwards, T; David Best, D; Irene Reamer, I; Phyllis Workman, P

    2008-02-13

    The performance of a glass used for immobilization of high-level nuclear waste (HLW) is generally quantified by its resistance to chemical degradation, or durability. The durability of a HLW glass is dependent on its composition. If crystalline phases form within a glass during cooling, the composition of the residual glass network is altered, therefore affecting the durability of the glass. Crystallization of nepheline (NaAlSiO{sub 4}) has been shown to adversely impact the durability of HLW glasses since it removes glass forming species (in this case, Al and Si) from the glass network. The propensity for nepheline crystallization in a HLW glass increases with increasing concentrations of Al{sub 2}O{sub 3} and Na{sub 2}O in the glass. Nepheline crystallization is therefore of concern for processing of HLW at the Defense Waste Processing Facility (DWPF) since the sludge waste streams at the Savannah River Site (SRS) can contain high concentrations of Al{sub 2}O{sub 3} and Na{sub 2}O. Currently, a 'nepheline discriminator' is included as a process control constraint at the DWPF. The nepheline discriminator relates the concentrations of SiO{sub 2}, Na{sub 2}O and Al{sub 2}O{sub 3} (as weight percentages in glass) to a critical value of 0.62. The discriminator defines a boundary line on the SiO{sub 2}-Na{sub 2}O-Al{sub 2}O{sub 3} ternary diagram above which (or toward the SiO{sub 2} corner of the ternary) nepheline is not predicted to crystallize in the glass upon quenching or slow cooling. The current equation uses only the concentrations of the SiO{sub 2}, Na{sub 2}O and Al{sub 2}O{sub 3} components in the glass in predicting whether or not nepheline is likely to crystallize. However, several other components have been shown to impact the propensity for nepheline crystallization, including B{sub 2}O{sub 3} and CaO among others. Therefore, the potential exists to further refine the nepheline discriminator to include these components. In addition, recently studied HLW

  17. Aquitard contaminant storage and flux resulting from dense nonaqueous phase liquid source zone dissolution and remediation

    EPA Science Inventory

    A one-dimensional diffusion model was used to investigate the effects of dense non-aqueous phase liquid (DNAPL) source zone dissolution and remediation on the storage and release of contaminants from aquitards. Source zone dissolution was represented by a power-law source depleti...

  18. Modeling and Properties of Modulated RF Signals Perturbed by Oscillator Phase Instabilities and Resulting Spectral Dispersion.

    DTIC Science & Technology

    1982-06-01

    characterization of the instability and its description in terms of some quantitative measures is essential [1.3], [1.4]. By phase/frequency instability...New Haven, Connecticut Elementary School: Hamilton Gramar School New Haven, Connecticut Graduated 1947 High School: Hillhouse High New Haven

  19. Dual phase transformation and resultant magnetic properties in Fe{sub 3}Pt thin films

    SciTech Connect

    Hsiao, S. N.; Lee, H. Y.; Chen, S. K.; Liu, S. H.

    2012-04-01

    Fifty-nm-thick Fe{sub 75}Pt{sub 25} thin films have been made on glass substrates by rf magnetron sputtering at room temperature, and subsequently annealed at 300 -700 deg. C (T{sub a}) for 1 h. The as-deposited Fe{sub 3}Pt film exhibits high magnetization of 1530 emu/cm{sup 3} and a disordered bcc structure, confirmed by high-resolution synchrotron radiation x-ray diffractometry. First-phase transformation from the bcc to disorder fcc structure occurs for samples annealed at 300 deg. C. With increasing of T{sub a} up to 375 deg. C, the film displays a nearly disordered fcc phase with low magnetization of 1083 emu/cm{sup 3}. The fcc phase changes to ordered L1{sub 2} structure for samples with T{sub a} {>=} 400 deg. C. The highly ordered L1{sub 2} phase with magnetization of 1270 emu/cm{sup 3} and coercivity of 66 Oe was obtained in Fe{sub 3}Pt film at 700 deg. C-annealing.

  20. Aquitard contaminant storage and flux resulting from dense nonaqueous phase liquid source zone dissolution and remediation

    EPA Science Inventory

    A one-dimensional diffusion model was used to investigate the effects of dense non-aqueous phase liquid (DNAPL) source zone dissolution and remediation on the storage and release of contaminants from aquitards. Source zone dissolution was represented by a power-law source depleti...

  1. Influence of Boundary Conditions on Regional Air Quality Simulations—Analysis of AQMEII Phase 3 Results

    EPA Science Inventory

    Chemical boundary conditions are a key input to regional-scale photochemical models. In this study, performed during the third phase of the Air Quality Model Evaluation International Initiative (AQMEII3), we perform annual simulations over North America with chemical boundary con...

  2. Group IVA phospholipase A2 regulates testosterone biosynthesis by murine Leydig cells and is required for timely sexual maturation

    PubMed Central

    Kurusu, Shiro; Sapirstein, Adam; Sawada, Harumi; Kawaminami, Mitsumori; Bonventre, Joseph V.

    2015-01-01

    In the present paper, we report that PLA2G4A (Group IVA phospholipase A2) is important in the development and function of rodent testes. Interstitial cells of rat testes had high PLA2 (phospholipase A2) activity that was very sensitive to the PLA2G4A-preferential inhibitor AACOCF3 (arachidonyl trifluoromethyl ketone). PLA2G4A protein was expressed primarily in the interstitial cells of wild-type mouse testes throughout maturation. Although Pla2g4a knockout (Pla2g4a−/− ) male mice are fertile, their sexual maturation was delayed, as indicated by cauda epididymal sperm count and seminal vesicle development. Delayed function of Pla2g4a−/− mice testes was associated with histological abnormalities including disorganized architecture, swollen appearance and fewer interstitial cells. Basal secretion of testosterone was attenuated significantly and steroidogenic response to hCG (human chorionic gonadotropin) treatment was reduced in Pla2g4a−/− mice compared with their Pla2g4a+/+ littermates during the sexual maturation period. Chemical inhibition of PLA2G4A activity by AACOCF3 or pyrrophenone significantly reduced hCG-stimulated testosterone production in cultured rat interstitial cells. AACOCF3 inhibited forskolin- and cAMP analogue-stimulated testosterone production. These results provide the first evidence that PLA2G4A plays a role in male testes physiology and development. These results may have implications for the potential clinical use of PLA2G4A inhibitors. PMID:21762109

  3. REFINEMENT OF THE NEPHELINE DISCRIMINATOR: RESULTS OF A PHASE II STUDY

    SciTech Connect

    Fox, K; Tommy Edwards, T

    2008-11-21

    Twenty five glass compositions were selected for a Phase II study to assess the potential for reducing the conservatism in the nepheline discriminator. The glass compositions were restricted to regions that fell within the validation ranges of the DWPF PCCS models. In addition, the liquidus temperature model was used to restrict the glass compositions so that they could all be melted at the same temperature. The nepheline discriminator was used to force the glass compositions into regions where nepheline formation was predicted to occur. The glasses were fabricated in the laboratory and characterized for crystallization and chemical durability after both quenching and slow cooling. Chemical analysis showed that the fabricated glasses met the target compositions. Nepheline was identified in one of the quenched glasses and several of the CCC glasses. There was no clear relationship between the types of crystallization that occurred in a particular glass and its location on the Al{sub 2}O{sub 3}-Na{sub 2}O-SiO{sub 2} ternary diagram. A partitioning algorithm was used to identify trends in crystallization behavior based on glass composition. Generally, for the CCC glasses MnO influenced the crystallization of spinels and B{sub 2}O{sub 3} and SiO{sub 2} influenced the crystallization of nepheline. Measured durability responses varied from acceptable to unacceptable depending on the glass composition and type and extent of crystallization that occurred. It was not possible to identify any linear effects of composition on chemical durability performance for this set of study glasses. The results were not sufficient to recommend modification of the current nepheline discriminator at this time. It is recommended that the next series of experiments continue to focus not only on compositional regions where the PCCS models are considered applicable (i.e., the model validation ranges), but also be restricted to compositional regions where acceptable glasses are predicted to be

  4. Macroscopic laws for immiscible two-phase flow in porous media: Results From numerical experiments

    NASA Astrophysics Data System (ADS)

    Rothman, Daniel H.

    1990-06-01

    Flow through porous media may be described at either of two length scales. At the scale of a single pore, fluids flow according to the Navier-Stokes equations and the appropriate boundary conditions. At a larger, volume-averaged scale, the flow is usually thought to obey a linear Darcy law relating flow rates to pressure gradients and body forces via phenomenological permeability coefficients. Aside from the value of the permeability coefficient, the slow flow of a single fluid in a porous medium is well-understood within this framework. The situation is considerably different, however, for the simultaneous flow of two or more fluids: not only are the phenomenological coefficients poorly understood, but the form of the macroscopic laws themselves is subject to question. I describe a numerical study of immiscible two-phase flow in an idealized two-dimensional porous medium constructed at the pore scale. Results show that the macroscopic flow is a nonlinear function of the applied forces for sufficiently low levels of forcing, but linear thereafter. The crossover, which is not predicted by conventional models, occurs when viscous forces begin to dominate capillary forces; i.e., at a sufficiently high capillary number. In the linear regime, the flow may be described by the linear phenomenological law ui = ΣjLijfj, where the flow rate ui of the ith fluid is related to the force fj applied to the jth fluid by the matrix of phenomenological coefficients Lij which depends on the relative concentrations of the two fluids. The diagonal terms are proportional to quantities commonly referred to as "relative permeabilities." The cross terms represent viscous coupling between the two fluids; they are conventionally assumed to be negligible and require special experimental procedures to observe in a laboratory. In contrast, in this numerical study the cross terms are straightforward to measure and are found to be of significant size. The cross terms are additionally observed to

  5. Long-Term Results From the Contura Multilumen Balloon Breast Brachytherapy Catheter Phase 4 Registry Trial

    SciTech Connect

    Cuttino, Laurie W.; Arthur, Douglas W.; Vicini, Frank; Julian, Thomas; Mukhopadhyay, Nitai

    2014-12-01

    Purpose: To describe the long-term outcomes from a completed, multi-institutional phase 4 registry trial using the Contura multilumen balloon (CMLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer. Methods and Materials: Three hundred forty-two evaluable patients were enrolled by 23 institutions between January 2008 and February 2011. All patients received 34 Gy in 10 fractions, delivered twice daily. Rigorous target coverage and normal tissue dose constraints were observed. Results: The median follow-up time was 36 months (range, 1-54 months). For the entire patient cohort of 342 patients, 10 patients experienced an ipsilateral breast tumor recurrence (IBTR). Eight of these IBTR were classified as true recurrences/marginal miss (TRMM), and 2 were elsewhere failures (EF). Local recurrence-free survival was 97.8% at 3 years. For the entire cohort, 88% of patients had good to excellent overall cosmesis. The overall incidence of infection was 8.5%. Symptomatic seroma was reported in only 4.4% of patients. A separate analysis was performed to determine whether improved outcomes would be observed for patients treated at high-volume centers with extensive brachytherapy experience. Three IBTR were observed in this cohort, only 1 of which was classified as a TRMM. Local recurrence-free survival at high-volume centers was 98.1% at 3 years. Overall cosmetic outcome and toxicity were superior in patients treated at high-volume centers. In these patients, 95% had good to excellent overall cosmesis. Infection was observed in only 2.9% of patients, and symptomatic seroma was reported in only 1.9%. Conclusion: Use of the CMLB for APBI delivery is associated with acceptable long-term local control and toxicity. Local recurrence-free survival was 97.8% at 3 years. Significant (grade 3) toxicity was uncommon, and no grade 4 toxicity was observed. Treatment at high-volume centers was associated

  6. Igneous Evolution of the Core and Mantle in the Parent Body of Group IVA Iron and Stony-Iron Meteorites

    NASA Astrophysics Data System (ADS)

    Scott, E. R. D.; McCoy, T. J.; Haack, H.; Taylor, G. J.

    1992-07-01

    Group IVA is comprised of 52 irons lacking silicates, two with trace amounts of silica (Gibeon and Bishop Canyon) and two stony irons (Steinbach and Sao Joao Nepomuceno), which have high but varied proportions of a pyroxene-tridymite intergrowth (Prinz et al., 1984). Despite their remarkable composition, these stony irons are not geological freaks lacking cosmochemical significance but important clues to the complexity of asteroidal processes. Metal: Our crystallization models for Fe-Ni-S magmas using distribution coefficients from Jones and Malvin (1990) with minor modifications from Haack and Scott (1992) show that the IVA irons formed by fractional crystallization of a melt with about 1-3 wt% S. Unlike previous authors we are able to model the Ir, Au, Ga, Ge, and P vs Ni trends in IVA concurrently. We include the formation of a second S-rich immiscible liquid during crystallization and find that our models can match IVA trends as well as those of group IIIAB, which has a higher S content. Siderophile concentrations in Steinbach and Sao Joao metal are, surprisingly, entirely appropriate for IVA irons with 9.1 and 8.0% Ni, showing that they formed in two separate places in the IVA body by mixing of silicates with metal that was fractionally crystallizing. Silicates: Steinbach and Sao Joao contain 10-60 vol% of SiO2 and ortho- and clinobronzite. In the sponge-like silicate- metal intergrowths, typical pore sizes are 2-6 mm though metal crystals are larger. Textures suggest co-crystallization of silicates from a liquid. Slight compositional differences between the two pyroxenes exist in both meteorites, with Steinbach pyroxenes being more FeO-rich. Formation of all the pyroxene by reaction between olivine and SiO2 (Prinz et al., 1984) fails to account for the minor elemental abundances in pyroxene, e.g. 0.25 wt% Al2O3. But the occurrence of SiO2 without pyroxene suggests that the SiO2-pyroxene intergrowths did not form entirely from SiO2-pyroxene eutectic or

  7. Thermal test results of the two-phase thermal bus technology d