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Sample records for results phase iva

  1. 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.

  2. Identification of a cellular repressor of transcription of the adenoviral late IVa(2) gene that is unaltered in activity in infected cells.

    PubMed

    Lin, H J; Flint, S J

    2000-11-25

    The gene encoding the adenovirus type 2 IVa(2) protein, a sequence-specific activator of transcription from the viral major late promoter, is itself transcribed only during the late phase of infection. We previously identified a cellular protein (IVa(2)-RF) that binds specifically to an intragenic sequence of the IVa(2) transcription unit. We now report that precise substitutions within the IVa(2)-RF-binding site that decreased binding affinity increased the efficiency of IVa(2) transcription in in vitro reactions containing IVa(2)-RF. Consistent with the conclusion that this cellular protein represses IVa(2) transcription, mutations that led to more efficient transcription in the presence of IVa(2)-RF were without effect in reactions lacking this cellular protein. No change in the concentration or activity of IVa(2)-RF could be detected in adenovirus-infected cells during the period in which the IVa(2) gene is transcribed. We therefore propose that restriction of IVa(2) transcription to the late phase is the result of titration of this cellular repressor as the number of copies of the IVa(2) promoter increases upon replication of the viral genome.

  3. 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.

  4. 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.

  5. ¹J(CH) couplings in Group 14/IVA tetramethyls from the gas-phase NMR and DFT structural study: a search for the best computational protocol.

    PubMed

    Nazarski, Ryszard B; Makulski, Włodzimierz

    2014-08-01

    Four tetramethyl compounds EMe4 (E = C, Si, Ge, and Pb) were studied by high-resolution NMR spectroscopy in gaseous and liquid states at 300 K. Extrapolation of experimental vapor-phase C-H J-couplings to a zero-pressure limit permitted determining the (1)J(0,CH)s in methyl groups of their nearly isolated molecules. Theoretical predictions of the latter NMR parameters were also performed in a locally dense basis sets/pseudopotential (Sn, Pb) approach, by applying a few DFT methods pre-selected in calculations of other gas-phase molecular properties of all these species and SnMe4 (bond lengths, C-H stretching IR vibrations). A very good agreement theory vs. experiment was achieved with some computational protocols for all five systems. The trends observed in their geometry and associated coupling constants ((1)J(CH)s, (2)J(HH)s) are discussed and rationalized in terms of the substituent-induced rehybridization of the methyl group (treated as a ligand) carbon, by using Bent's rule and the newly proposed, theoretically derived values of the Mulliken electronegativity (χ) of related atoms and groups. All these χ data for the Group-14/IVA entities were under a lot of controversy for a very long time. As a result, the recommended χ values are semi-experimentally confirmed for the first time and only a small correction is suggested for χ(Ge) and χ(GeMe3).

  6. Lymphadenectomy in locally advanced cervical cancer study (LiLACS): Phase III clinical trial comparing surgical with radiologic staging in patients with stages IB2-IVA cervical cancer.

    PubMed

    Frumovitz, Michael; Querleu, Denis; Gil-Moreno, Antonio; Morice, Philippe; Jhingran, Anuja; Munsell, Mark F; Macapinlac, Homer A; Leblanc, Eric; Martinez, Alejandra; Ramirez, Pedro T

    2014-01-01

    Radiation treatment planning for women with locally advanced cervical cancer (stages IB2-IVA) is often based on positron emission tomography (PET). PET, however, has poor sensitivity in detecting metastases in aortocaval nodes. We have initiated a study with the objective of determining whether pre-therapeutic laparoscopic surgical staging followed by tailored chemoradiation improves survival as compared with PET/computed tomography (CT) radiologic staging alone followed by chemoradiation. This international, multicenter phase III trial will enroll 600 women with stages IB2-IVA cervical cancer and PET/CT findings showing fluorodeoxyglucose-avid pelvic nodes and fluorodeoxyglucose-negative para-aortic nodes. Eligible patients will be randomized to undergo either pelvic radiotherapy with chemotherapy (standard-of-care arm) or surgical staging via a minimally invasive extraperitoneal approach followed by tailored radiotherapy with chemotherapy (experimental arm). The primary end point is overall survival. Secondary end points are disease-free survival, short- and long-term morbidity with pre-therapeutic surgical staging, and determination of anatomic locations of metastatic para-aortic nodes in relationship to the inferior mesenteric artery. We believe this study will show that tailored chemoradiation after pre-therapeutic surgical staging improves survival as compared with chemoradiation based on PET/CT in women with stages IB2-IVA cervical cancer.

  7. 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.

  8. 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.

  9. Viral DNA synthesis-dependent titration of a cellular repressor activates transcription of the human adenovirus type 2 IVa2 gene.

    PubMed

    Iftode, C; Flint, S J

    2004-12-21

    Synthesis of progeny DNA genomes in cells infected by human subgroup C adenoviruses leads to several changes in viral gene expression. These changes include transcription from previously silent, late promoters, such as the IV(a2) promoter, and a large increase in the efficiency of major-late (ML) transcription. Some of these changes appear to take place sequentially, because the product of the IV(a2) gene has been implicated in stimulation of ML transcription. Our previous biochemical studies suggested that IV(a2) transcription is regulated by viral DNA synthesis-dependent relief of transcriptional repression by a cellular protein that we termed IV(a2)-RF. To test the relevance of such a repressor-titration mechanism during the viral infectious cycle, we introduced into the endogenous IV(a2) promoter two mutations that impair in vitro-binding of IV(a2)-RF, but introduce no change (Rep7) or one conservative amino acid substitution (Rep6) into the overlapping coding sequence for the viral DNA polymerase. The results of run-on transcription assays indicated that both mutations induced earlier-than-normal and more efficient IV(a2) transcription. Both mutations were also observed to result in modest increases in the efficiency of viral DNA synthesis. However, measurement of the concentration of IV(a2) transcripts as a function of IV(a2) template concentration demonstrated that the Rep mutations increased by up to 60-fold the efficiency with which IV(a2) templates were used during the initial period of the late phase of infection, as predicted by the repressor titration hypothesis. These mutations also increased the efficiency of ML transcription in infected cells.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. Phase II Trial of Hyperfractionated IMRT and Concurrent Weekly Cisplatin for Stage III and IVa Head and Neck Cancer

    PubMed Central

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

    2010-01-01

    Purpose 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). Patients and Methods Patients received hyperfractionated intensity modulated radiation therapy (HIMRT) in 1.25 Gy fractions bid 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/m2/week was started week 1. Patients completed the Quality of Life Radiation Therapy Instrument prior to (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 Thirty of 39 patients (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 versus 3.9 EOT. By month 1, H&N QOL returned near baseline: mean 6.2 (sd=1.7). 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. PMID:20378262

  15. Cis and trans activation of adenovirus IVa2 gene transcription.

    PubMed Central

    Natarajan, V; Salzman, N P

    1985-01-01

    The transcriptional control region of the adenovirus IVa2 promoter was analyzed by cloning this promoter in front of a gene coding for bacterial chloramphenicol acetyl transferase (CATase) and estimating levels of CATase and IVa2 promoter specific RNA synthesized after transfection. To produce detectable amounts of CATase with the IVa2 promoter, an enhancer has to be present in cis. In the absence of enhancer sequences, the adenovirus E1A gene can not stimulate CATase synthesis. When cells were transfected with plasmids containing enhancer sequences and various IVa2 mutant promoters upstream of the CAT gene, we observed that CATase activity was not reduced significantly even after deletion of all sequences upstream of the RNA initiation site. Synthesis of IVa2 specific RNA was dependent on plasmids containing an enhancer (SV40 72 bp repeat) that was present in cis. In the absence of enhancer sequences, co-transfection to provide the adenovirus E1A gene in trans also stimulated IVa2 RNA synthesis. When HeLa cells were transfected with various deletion mutants with an enhancer in cis it was seen that sequences -38 to -64 base pairs upstream of the RNA initiation site are necessary for efficient transcription. The E1A gene in trans and an enhancer in cis have an additive effect on RNA synthesis from both IVa2 and major late promoters. The basis for the conflicting results between transcription and CATase synthesis is discussed. Images PMID:2989786

  16. Hyperbaric oxygen therapy for carcinoma of the cervix - Stages IIB, IIIA, IIIB, and IVA: results of a randomized study by the radiation therapy oncology group

    SciTech Connect

    Brady, L.W.; Plenk,H.P.; Hanley, J.A.

    1981-08-01

    A total of 65 patients with Stage IIB, IIIA, IIIB or IVA carcinoma of the cervix were randomized to receive conventional radiation therapy in air or hyperbaric oxygen therapy with radiation at optimal schedules. Seven patients could not be evaluated. Of the 19 patients treated in oxygen, 14 (73%) were living or had died without evidence of disease. Of the 29 patients treated with radiation alone 15 (52%) were alive or had died without evidence of tumor. Two of 29 patients treated in air and 5 of 19 patients treated in oxygen were dead of complications or intercurrent disease. No significant difference in survival could be demonstrated.

  17. 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.

  18. 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.

  19. 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. PMID:27366102

  20. 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

  1. 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.

  2. 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).

  3. Assessment of the IVA3 code for multifield flow simulation

    NASA Astrophysics Data System (ADS)

    Stewart, H. B.

    1995-07-01

    This report presents an assessment of the IVA3 computer code for multifield flow simulation, as applied to the premixing phase of a hypothetical steam explosion in a water-cooled power reactor. The first section of this report reviews the derivation of the basic partial differential equations of multifield modeling, with reference to standard practices in the multiphase flow literature. Basic underlying assumptions and approximations are highlighted, and comparison is made between IVA3 and other codes in current use. Although Kolev's derivation of these equations is outside the mainstream of the multiphase literature, the basic partial differential equations are in fact nearly equivalent to those in other codes. In the second section, the assumptions and approximations required to pass from generic differential equations to a specific working form are detailed. Some modest improvements to the IVA3 model are suggested. In Section 3, the finite difference approximations to the differential equations are described. The discretization strategy is discussed with reference to numerical stability, accuracy, and the role of various physical phenomena - material convection, sonic propagation, viscous stress, and interfacial exchanges - in the choice of discrete approximations. There is also cause for concern about the approximations of time evolution in some heat transfer terms, which might be adversely affecting numerical accuracy. The fourth section documents the numerical solution method used in IVA3. An explanation for erratic behavior sometimes observed in the first outer iteration is suggested, along with possible remedies. Finally, six recommendations for future assessment and improvement of the IVA3 model and code are made.

  4. 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.

  5. Protein-protein interaction domains of Bacillus subtilis DivIVA.

    PubMed

    van Baarle, Suey; Celik, Ilkay Nazli; Kaval, Karan Gautam; Bramkamp, Marc; Hamoen, Leendert W; Halbedel, Sven

    2013-03-01

    DivIVA proteins are curvature-sensitive membrane binding proteins that recruit other proteins to the poles and the division septum. They consist of a conserved N-terminal lipid binding domain fused to a less conserved C-terminal domain. DivIVA homologues interact with different proteins involved in cell division, chromosome segregation, genetic competence, or cell wall synthesis. It is unknown how DivIVA interacts with these proteins, and we used the interaction of Bacillus subtilis DivIVA with MinJ and RacA to investigate this. MinJ is a transmembrane protein controlling division site selection, and the DNA-binding protein RacA is crucial for chromosome segregation during sporulation. Initial bacterial two-hybrid experiments revealed that the C terminus of DivIVA appears to be important for recruiting both proteins. However, the interpretation of these results is limited since it appeared that C-terminal truncations also interfere with DivIVA oligomerization. Therefore, a chimera approach was followed, making use of the fact that Listeria monocytogenes DivIVA shows normal polar localization but is not biologically active when expressed in B. subtilis. Complementation experiments with different chimeras of B. subtilis and L. monocytogenes DivIVA suggest that MinJ and RacA bind to separate DivIVA domains. Fluorescence microscopy of green fluorescent protein-tagged RacA and MinJ corroborated this conclusion and suggests that MinJ recruitment operates via the N-terminal lipid binding domain, whereas RacA interacts with the C-terminal domain. We speculate that this difference is related to the cellular compartments in which MinJ and RacA are active: the cell membrane and the cytoplasm, respectively.

  6. Protein-Protein Interaction Domains of Bacillus subtilis DivIVA

    PubMed Central

    van Baarle, Suey; Celik, Ilkay Nazli; Kaval, Karan Gautam; Bramkamp, Marc

    2013-01-01

    DivIVA proteins are curvature-sensitive membrane binding proteins that recruit other proteins to the poles and the division septum. They consist of a conserved N-terminal lipid binding domain fused to a less conserved C-terminal domain. DivIVA homologues interact with different proteins involved in cell division, chromosome segregation, genetic competence, or cell wall synthesis. It is unknown how DivIVA interacts with these proteins, and we used the interaction of Bacillus subtilis DivIVA with MinJ and RacA to investigate this. MinJ is a transmembrane protein controlling division site selection, and the DNA-binding protein RacA is crucial for chromosome segregation during sporulation. Initial bacterial two-hybrid experiments revealed that the C terminus of DivIVA appears to be important for recruiting both proteins. However, the interpretation of these results is limited since it appeared that C-terminal truncations also interfere with DivIVA oligomerization. Therefore, a chimera approach was followed, making use of the fact that Listeria monocytogenes DivIVA shows normal polar localization but is not biologically active when expressed in B. subtilis. Complementation experiments with different chimeras of B. subtilis and L. monocytogenes DivIVA suggest that MinJ and RacA bind to separate DivIVA domains. Fluorescence microscopy of green fluorescent protein-tagged RacA and MinJ corroborated this conclusion and suggests that MinJ recruitment operates via the N-terminal lipid binding domain, whereas RacA interacts with the C-terminal domain. We speculate that this difference is related to the cellular compartments in which MinJ and RacA are active: the cell membrane and the cytoplasm, respectively. PMID:23264578

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. The IVA Parent Body: Evidence from Silicate-Bearing Group IVA Iron Meteorites

    NASA Astrophysics Data System (ADS)

    Ulff-Moller, F.; Kallemeyn, G. W.; Rasmussen, K. L.

    1992-07-01

    The IVA iron meteorites Steinbach (SB), Sao Joao Nepomuceno (SJN), Gibeon and Bishop Canyon are unusual in their contents of silicates. SB is particularly rich in silicates (ca. 50 wt%) and was long classified as a stony iron (Dorfler et al., 1965) but the metal fraction is typical of group IVA iron meteorites (Schaudy et al., 1972). The SB and SJN contain low-Ca pyroxene and tridymite in roughly equal proportions, whereas only tridymite is found in the two other meteorites. Reid et al. (1974) found that coexisting orthopyroxene and clinopyroxenes in SB (En 85) were formed in a narrow two-phase field at 1200 degrees C and preserved by comparatively rapid cooling. We present cooling rate estimates as well as minor element data for the silicates obtained by electron microprobe and trace elements (REE and siderophiles) for the bulk silicate fraction by INAA. The coarse granular texture of the silicates and the presence of finely dispersed sulfide inclusions in the pyroxenes might suggest a cumulate origin, but the high proportion of tridymite combined with MgO-rich pyroxene is unusual if a chondritic magma is assumed. One way of forming excess tridymite is by extreme reduction of a pallasite-type metal/olivine mixture. Our INAA data on SB bulk silicates show a pattern of REE and Sc, Cr, and Mn, which is qualitatively consistent with orthopyroxene that crystallized from a moderately evolved magma with chondritic REE levels. The incompatible elements (including Cr!) in SB pyroxene are correlated and vary up to a factor of 5 (eg., Ti and Al), whereas Ca shows a bimodal variation corresponding roughly to the coexisting orthopyroxene and clinopyroxene. The minor element variations in SB pyroxene thus resemble magmatic zoning. The SJN pyroxene is marginally more MgO-rich (En 86) and shows a similar bimodal Ca distribution although it is possibly one phase. If correct, this suggests slower cooling at a higher temperature than SB. References: Dorfler G., Hecht F. and

  18. 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…

  19. 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.

  20. 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. PMID:27331011

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  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.

  7. 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.

  8. 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

  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. 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.

  11. 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.

  12. Newberry Volcano EGS Demonstration - Phase I Results

    SciTech Connect

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

    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

  13. 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

  14. The early formation of the IVA iron meteorite parent body

    NASA Astrophysics Data System (ADS)

    Blichert-Toft, Janne; Moynier, Frédéric; Lee, Cin-Ty A.; Telouk, Philippe; Albarède, Francis

    2010-08-01

    The IVA iron meteorites are magmatic cumulates from the core of a small asteroid, which broke apart ˜ 400 Ma ago. As the depletion of this planetary body in volatile elements is expected to be reflected in high U/Pb ratios of its minerals, we embarked on analyzing the isotope composition of Pb in the cm-sized troilite inclusions of Muonionalusta and Gibeon, both iron meteorites belonging to the IVA family. The bulk of the data for nine troilite subsamples of Muonionalusta scatter with an apparent age of 4.57 Ga, which is shown to reflect the presence of both primordial and common terrestrial Pb components, in addition to radiogenic Pb. The most radiogenic subsample, however, has fractions with 206Pb/ 204Pb ratios as high as over 1000 and gives a statistically significant 207Pb*/ 206Pb* age of 4565.3 ± 0.1 Ma (MSWD = 0.08), consistent with the 182Hf- 182W metal-silicate segregation age of 2.4 ± 2.0 Ma. These data make the age of Muonionalusta the oldest documented yet for all differentiated bodies in the Solar System and constitute the first high-precision Pb-Pb age determined for crystallization of a phase contained within an iron meteorite group, hence advancing our understanding of early Solar System chronology. Using literature values for the cooling rate, and assuming a closure temperature for Pb of 300 °C, it is further estimated that the IVA parent body accreted within 1 Ma of CAI formation and had cooled to the Pb closure temperature within an additional 1-2 Ma. The overlap between the high-precision Pb-Pb and Hf-W ages points to a small, or rapidly fragmented, planetary body. The isotopic composition of Pb in Gibeon troilite yields a significantly younger age of 4544 ± 7 Ma (MSWD = 1.5), consistent with evidence from the 107Pd- 107Ag chronometer, but we believe this age has been reset by melting upon shock. One puzzling observation is that the apparent 232Th/ 238U of Muonionalusta troilite is particularly low (˜ 0.32), requiring a mechanism capable of

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Mucopolysaccharidosis IVA: Identification of a common missense mutation I113F in the N-Acetylgalactosamine-6-sulfate sulfatase gene

    SciTech Connect

    Tomatsu, Shunji; Fukuda, Seiji; Rezvi, Maruf

    1995-09-01

    Mucopolysaccharidosis IVA is an autosomal recessive lysosomal storage disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). The recent isolation and characterization of cDNA and genomic sequences encoding GALNS has facilitated identification of the molecular lesions that cause MPS IVA. We identified a common missense mutation among Caucasian MPS IVA patients. The mutation was originally detected by SSCP, and successive sequencing revealed an A{yields}T transversion at nt 393. This substitution altered the isoleucine at position 113 to phenylalanine (I113F) in the 622 amino acid GALNS protein and was associated with a severe phenotype in a homozygote. Compound heterogzygotes with one I113F-allele mutation have a wide range of clinical phenotypes. Transfection experiments in GALNS-deficient fibroblasts revealed that the mutation drastically reduces the enzyme activity of GALNS. Allele-specific oligonucleotide or SSCP analysis indicated that this mutation accounted for 22.5% (9/40) of unrelated MPS IVA chromosomes from 23 Caucasian patients, including 6 consanguineous cases. Of interest, the I1e 113{yields}Phe substitution occurred in only Caucasian MPS IVA patients and in none of the GALNS alleles of 20 Japanese patients. These findings identify a frequent missense mutation among MPS IVA patients of Caucasian ancestry that results in severe MPS IVA when homoallelic, and will facilitate molecular diagnosis of most such patients and identification of heterozygous carriers. In addition to this common mutation, 10 different point mutations and 2 small deletions were detected, suggesting allelic heterogeneity in GALNS gene. 32 refs., 2 figs., 3 tabs.

  20. Phase Transition Signature Results from PHENIX

    SciTech Connect

    Mitchell, J.e.; PHENIX Collaboration

    2009-06-08

    The PHENIX experiment has conducted searches for the QCD critical point with measurements of multiplicity fluctuations, transverse momentum fluctuations, event-by-event kaon-to-pion ratios, elliptic flow, and correlations. Measurements have been made in several collision systems as a function of centrality and transverse momentum. The results do not show significant evidence of critical behavior in the collision systems and energies studied, although several interesting features are discussed.

  1. 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.

  2. 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

  3. 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.

  4. 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. ().

  5. 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.

  6. 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

  7. 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 Astrophysics Data System (ADS)

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

    2006-06-01

    Group IVA is a large magmatic group of iron meteorites. The mean Δ 17O (=δ 17O - 0.52·δ 18O) of the silicates is ˜+1.2‰, similar to the highest values in L chondrites and the lowest values in LL chondrites; δ 18O 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 (˜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 (˜1770 K) low-viscosity melt quickly moved through channels in the porous asteroid to form a core. Two members of the IVA group, São João Nepomuceno (hereafter, SJN) and Steinbach, contain moderate amounts of orthopyroxene and silica, and minor amounts of low-Ca clinopyroxene. Even though SJN formed after ˜26% crystallization and Steinbach formed after ˜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 into IVA irons after the initial magma crystallized. Because the

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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).

  16. 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

  17. 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.

  18. 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.

  19. 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.

  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. 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.

  2. 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.

  3. 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.

  4. Cisplatin and Radiation Therapy With or Without Triapine in Treating Patients With Previously Untreated Stage IB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer

    ClinicalTrials.gov

    2016-03-25

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB2 Cervical Cancer; Stage II Vaginal Cancer; Stage IIA1 Cervical Cancer; Stage IIA2 Cervical Cancer; Stage IIB Cervical Cancer; Stage III Vaginal Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Vaginal Adenocarcinoma; Vaginal Adenosquamous Carcinoma; Vaginal Squamous Cell Carcinoma

  5. Phase quality map based on local multi-unwrapped results for two-dimensional phase unwrapping.

    PubMed

    Zhong, Heping; Tang, Jinsong; Zhang, Sen

    2015-02-01

    The efficiency of a phase unwrapping algorithm and the reliability of the corresponding unwrapped result are two key problems in reconstructing the digital elevation model of a scene from its interferometric synthetic aperture radar (InSAR) or interferometric synthetic aperture sonar (InSAS) data. In this paper, a new phase quality map is designed and implemented in a graphic processing unit (GPU) environment, which greatly accelerates the unwrapping process of the quality-guided algorithm and enhances the correctness of the unwrapped result. In a local wrapped phase window, the center point is selected as the reference point, and then two unwrapped results are computed by integrating in two different simple ways. After the two local unwrapped results are computed, the total difference of the two unwrapped results is regarded as the phase quality value of the center point. In order to accelerate the computing process of the new proposed quality map, we have implemented it in a GPU environment. The wrapped phase data are first uploaded to the memory of a device, and then the kernel function is called in the device to compute the phase quality in parallel by blocks of threads. Unwrapping tests performed on the simulated and real InSAS data confirm the accuracy and efficiency of the proposed method. PMID:25967782

  6. Phase quality map based on local multi-unwrapped results for two-dimensional phase unwrapping.

    PubMed

    Zhong, Heping; Tang, Jinsong; Zhang, Sen

    2015-02-01

    The efficiency of a phase unwrapping algorithm and the reliability of the corresponding unwrapped result are two key problems in reconstructing the digital elevation model of a scene from its interferometric synthetic aperture radar (InSAR) or interferometric synthetic aperture sonar (InSAS) data. In this paper, a new phase quality map is designed and implemented in a graphic processing unit (GPU) environment, which greatly accelerates the unwrapping process of the quality-guided algorithm and enhances the correctness of the unwrapped result. In a local wrapped phase window, the center point is selected as the reference point, and then two unwrapped results are computed by integrating in two different simple ways. After the two local unwrapped results are computed, the total difference of the two unwrapped results is regarded as the phase quality value of the center point. In order to accelerate the computing process of the new proposed quality map, we have implemented it in a GPU environment. The wrapped phase data are first uploaded to the memory of a device, and then the kernel function is called in the device to compute the phase quality in parallel by blocks of threads. Unwrapping tests performed on the simulated and real InSAS data confirm the accuracy and efficiency of the proposed method.

  7. 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.

  8. 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. PMID:22231379

  9. 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.

  10. Retrospective Analysis of the Survival Benefit of Induction Chemotherapy in Stage IVa-b Nasopharyngeal Carcinoma

    PubMed Central

    Xiao, Yao; Tang, Jie; OuYang, Pu-Yun; Su, Zhen; Xie, Fang-Yun

    2016-01-01

    Purpose 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. Patients and Methods 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. Results 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. Conclusions 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

  11. Interferometric SAR phase difference calibration: Methods and results

    SciTech Connect

    Bickel, D.L.; Hensley, W.H.

    1993-12-31

    This paper addresses the steps necessary to determine and maintain the phase calibration of a two-channel interferometric synthetic aperture radar (IFSAR). The method, setup, and accuracy of four different calibration techniques are compared. The most novel technique involves pointing the interferometric baseline at nadir and imaging a lake surface. The other techniques include measuring various flat surfaces in traditional side-looking IFSAR maps, in-flight closed-loop calibration path measurements, and static laboratory measurements. Initial results indicate that, using combinations of these measurements, it is possible to maintain the interferometric phase calibration of Sandia National Laboratories` K{sub U} Band IFSAR to better than 3 degrees. The time variability of various parts of the calibration and requirements for recalibration are also discussed.

  12. 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.

  13. Plutonium Immobilization Program -- Cold pour Phase 1 test results

    SciTech Connect

    Hamilton, L.

    2000-01-18

    The Plutonium Immobilization Project will disposition excess weapons grade plutonium. It uses the can-in-canister approach that involves placing plutonium-ceramic pucks in sealed cans that are then placed into Defense Waste Processing Facility canisters. These canisters are subsequently filled with high-level radioactive waste glass. This process puts the plutonium in a stable form and makes it unattractive for reuse. A cold (non-radioactive) glass pour program was performed to develop and verify the baseline design for the canister and internal hardware. This paper describes the Phase 1 scoping test results.

  14. 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.

  15. A function of DivIVA in Listeria monocytogenes division site selection.

    PubMed

    Kaval, Karan Gautam; Rismondo, Jeanine; Halbedel, Sven

    2014-11-01

    The cell division protein DivIVA influences protein transport via the accessory SecA2 secretion route in Listeria monocytogenes. In contrast, DivIVA from the closely related bacterium Bacillus subtilis contributes to division site selection via the MinCDJ system. However, no classical min phenotype, i.e. filamentation and minicell production was observed with a listerial ΔdivIVA mutant. This has prompted the speculation that division site selection is DivIVA-independent in L. monocytogenes. We addressed this question with genetic, cytological and bacterial two-hybrid experiments and the data obtained correct this view. DivIVA not only binds to MinJ but also directly interacts with MinD. Experiments with fluorescently tagged proteins showed that localization of MinC and MinD was clearly DivIVA-dependent, whereas localization of MinJ was not. An impact of DivIVA on cell division was confirmed by careful comparisons of cell size distributions of divIVA and secA2 mutants. Gene deletion studies and epistasis experiments consistently reinforced these findings, and also revealed that MinJ must have a DivIVA-independent function. The frequency of minicell formation is low in L. monocytogenes min mutants. However, since listerial minicells might be useful as carriers for the introduction of therapeutic compounds into eukaryotic cells, we present a strategy how minicell frequency can be increased.

  16. 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. PMID:1916087

  17. 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

  18. 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.

  19. 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.

  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. 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.

  2. 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

  3. 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.

  4. 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; Rose, Fred; Zhang, Yuanchong; Wilson Michael J.; Rossow, William

    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

  5. 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.

  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, "Case…

  7. 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.

  8. 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)

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Magnetic beads-based enzymatic spectrofluorometric assay for rapid and sensitive detection of antibody against ApxIVA of Actinobacillus pleuropneumoniae.

    PubMed

    Wei, Bo; Li, Fang; Yang, Huicui; Yu, Lei; Zhao, Kaihong; Zhou, Rui; Hu, Yonggang

    2012-05-15

    In this paper, a simple, easily-operated and enzyme-amplified fluorescence immunoassay method using magnetic particles for the detection of antibody against Actinobacillus pleuropneumoniae (APP) has been presented. The A protein of APP Repeats-in-Toxin IV (ApxIVA) with high specificity to the APP species was immobilized onto the magnetic bead surfaces. Horseradish peroxidase (HRP), which can catalyze the substrate 4-hydroxyphenylacetic acid (p-HPA), generating fluorescent bi-p, p'-hydroxyphenylacetic acid (DBDA), was selected as an enzymatic-amplified tracer. The ApxIVA antibody was detected for the presence of APP infection by measuring the fluorescence intensity of DBDA. Under optimal conditions, the calibration plot obtained for standard positive serum was approximately linear within the dilution range 1:160-1:5120. The limit of detection (LOD) for the assay was 1:10240, considerably lower than that of ApxIVA-ELISA (1:320) (S/N=3). A series of repeatability measurements of using 1:320-fold diluted standard positive serum gave reproducible results with a relative standard deviation (RSD) of 4.8% (n=11). The ability of the immunosensor to analyze clinical samples was tested on porcine sera. The immunosensor yielded an efficiency of 89.7%, sensitivity of 90.9% and specificity of 89.3% compared with ApxIVA-ELISA.

  14. 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.

  15. 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.

  16. Phase closure nulling: results from the 2009 campaign

    NASA Astrophysics Data System (ADS)

    Duvert, Gilles; Malbet, Fabien; Chelli, Alain; Millan-Gabet, Rafael; Monnier, John D.; Schaefer, Gail H.

    2010-07-01

    We present here a new observational technique, Phase Closure Nulling (PCN), which has the potential to obtain very high contrast detection and spectroscopy of faint companions to bright stars. PCN consists in measuring closure phases of fully resolved objects with a baseline triplet where one of the baselines crosses a null of the object visibility function. For scenes dominated by the presence of a stellar disk, the correlated flux of the star around nulls is essentially canceled out, and in these regions the signature of fainter, unresolved, scene object(s) dominates the imaginary part of the visibility in particular the closure phase. We present here the basics of the PCN method, the initial proof-of-concept observation, the envisioned science cases and report about the first observing campaign made on VLTI/AMBER and CHARA/MIRC using this technique.

  17. Finite seismic source inferred from stopping phases - preliminary results

    NASA Astrophysics Data System (ADS)

    Kolář, P.; Růžek, B.

    2009-04-01

    Seismic activity in West Bohemia region is the most important seismic phenomenon in the territory of the Czech Republic. It is continuously monitored by WEBNET seismic network and consequently, the seismic records are object of intensive studies. However, due to "continuous" data flow and remarkable event number (up to 10E4), data processing is mostly oriented on routine and/or semi-automatic operation (events identification, location, bulletin compilation, etc) or on some global statistic features as e.g. temporal-spatial distribution of released energy. Detailed study on seismic source maybe therefore performed on selected sets of relatively strong events: we have identified and interpreted stopping phases. Stopping phases theory supposes radiation of seismic waves from a planar finite source in such a way, that effectively only 3 points along the source area contribute to the waveform: (i) first arrival wave, which corresponds to the start of the rupture process, and (ii) two so called stopping phases, which correspond to stopping points situated on the edge of the ruptured source area. Following inversion is based on kinematic principles, since timing of stopping phases and first arrivals must hold relations given by the geometry of the seismic source, measuring geometry, and by delays introduced by the considered velocity model (approach by Imanishi and Takeo, 1998, 2002). We have developed and tested computer code based on above mentioned theory, tested the code using synthetic data (finite seismic kinematic model designated by Boathwright, 1980, was considered) and performed pilot calculations of real data. It follows from the first calculations: the inversion itself is more or less routine process, but the identification of stop phases in the seismogram is rather problematic and must be done interactively for each of processed event. As the stop phases identification and their picking is crucial in our case, computer tools has been developed to be user

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. Autonomous Airborne Refueling Demonstration Phase I Flight Test Results

    NASA Technical Reports Server (NTRS)

    Dibley, Ryan

    2007-01-01

    This viewgraph presentation provides flight test results of the automatic in-flight refueling of an Uninhabited Aerial Vehicle (UAV) using an automated hose-and-drogue refueling method. The program objective was to demonstrate one fully automatic engagement between the receiver and tanker aircraft. Systems involved, concept of operations, results and conclusions are included.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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. PMID:21506915

  20. 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

  1. Transmission and phase balancing of alternating phase-shifting masks (5x): theoretical and experimental results

    NASA Astrophysics Data System (ADS)

    Griesinger, Uwe A.; Pforr, Rainer; Knobloch, Juergen; Friedrich, Christoph M.

    1999-12-01

    Dual trench alternating phase shifting masks with an optimized value of the so-called shallow trench depth represents an interesting approach to overcome aerial image imbalances. In order to get a better understanding of the possibilities and limits of this approach, especially for 5X reduction, theoretical and experimental investigations were accomplished. In this paper experimental data obtained from 5X dual trench type alternating PSMs, using DUV-lithography are introduced and compared with 3D-mask simulations. The masks were fabricated with different etch depths and contain parts of typical DRAM patterns. Besides the transmission balancing also the phase balancing has an important influence on the effective process window of an alternating PSM. The effective phase error can be measured with an AIMS-system (MSM100). The comparison with simulated data allows the determination of the phase error. In a second step the influence of different balancing methods on phase and transmission were investigated with the TEMPEST mask simulator for unpolarized light. The optimization of the balancing with respect to the CD-bias, undercut and etch depth will be shown and a first approach of a sensitivity analysis will be presented.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Phase transition kinetics in DIET of vanadium pentoxide. I. Experimental results

    NASA Astrophysics Data System (ADS)

    Ai, R.; Fan, H.-J.; Marks, L. D.

    1993-01-01

    Experimental results of the kinetics of phase transformation in vanadium pentoxide during surface loss of oxygen from electron irradiation are described. Phase transformations under three different regimes were examined: (a) low flux; (b) intermediate flux and (c) high flux. Different phase transformation routes were observed under different fluxes. In a companion paper, numerical calculations are presented demonstrating that these results are due to a mixed interface/diffusion controlled phase transition pumped by surface oxygen loss.

  7. 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.

  8. 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.

  9. Mucopolysaccharidosis IVA: Four new exonic mutations in patients with N-acetylgalactosamine-6-sulfate sulfatase deficiency

    SciTech Connect

    Tomatsu, Shunji; Fukuda, Seiji; Yamagishi, Atsushi

    1996-05-01

    We report four new mutations in Japanese patients with mucopolysaccharidosis IVA (MPSIVA) who were heterozygous for a common double gene deletion. A nonsense mutation of CAG to TAG at codon 148 in exon 4 was identified, resulting in a change of Q to a stop codon and three missense mutations: V (GTC) to A (GCC) at codon 138 in exon 4, P (CCC) to S (TCC) at codon 151 in exon 5, and P (CCC) to L (CTC) at codon 151 in exon 5. Introduction of these mutations into the normal GALNS cDNA and transient expression in cultured fibroblasts resulted in a significant decrease in the enzyme activity. V138A and Q148X mutations result in changes of restriction site, which were analyzed by restriction-enzyme assay. P151S and P151L mutations that did not alter the restriction site were detected by direct sequencing or allele specific oligohybridization. Detection of the double gene deletion was initially done using Southern blots and was confirmed by PCR. Haplotypes were determined using seven polymorphisms to the GALNS locus in families with the double gene deletion. Haplotype analysis showed that the common double gene deletion occurred on a single haplotype, except for some variation in a VNTR-like polymorphism. This finding is consistent with a common founder for all individuals with this mutation. 48 refs., 5 figs., 1 tab.

  10. 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

    2016-11-03

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB2 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

  11. 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.

  12. 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.

  13. Loop-mediated isothermal amplification targeting the apxIVA gene for detection of Actinobacillus pleuropneumoniae.

    PubMed

    Yang, Wang; Pin, Chen; Haibing, Guo; Yang, Chen; Hui, Liu; Qigai, He

    2009-11-01

    Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method performed under isothermal conditions with high specificity and efficiency. We developed a diagnostic method based on LAMP for detection of Actinobacillus pleuropneumoniae. Using six specific primers targeting the apxIVA gene, the LAMP assay rapidly amplified the target gene within 30 min, requiring only a laboratory water bath for the reaction to occur. The resulting amplificon was visualized by adding SYBR Green I to the mixture. The results obtained from testing 15 A. pleuropneumoniae reference strains and other seven bacterial species strains showed that the LAMP was as specific as and 10 times more sensitive than nested PCR. Sixty-five tonsil samples were collected from 65 healthy pigs. All the samples were negative for A. pleuropneumoniae by immunomagnetic separation-based (IMS) bacterial isolation, nested PCR and LAMP, respectively. Meanwhile, 115 tonsil samples were also collected from 115 pigs with apparent respiratory problems. Twenty-two were positive by IMS bacterial isolation. All the samples that were positive by IMS bacterial isolation were also positive by nested PCR and LAMP. The LAMP assay demonstrated exceptionally higher sensitivity than nested PCR by picking up 14 additional positive cases (chi(2) test, P<0.0001); we concluded that LAMP was a highly sensitive and reliable method for detection of A. pleuropneumoniae infection.

  14. 187Re-187Os, 190Pt-186Os Isotopic and Highly Siderophile Element Systematics of Group IVA Irons

    NASA Astrophysics Data System (ADS)

    Walker, R. J.; McCoy, T. J.; Schulte, R. F.; McDonough, W. F.; Ash, R. D.

    2005-03-01

    High precision analysis of highly siderophile elements in group IVA irons are generally suggestive of simple crystal-liquid fractination. Fuzzy Creek is not consistent with this interpretation. Ungrouped irons Nedagolla and EET 83230 have some chemical characteristic consistent with IVA.

  15. 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.

  16. 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

  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. 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...

  19. 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…

  20. 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.

  1. 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…

  2. 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.

  3. 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.

  4. 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, 2014 CFR

    2014-07-01

    ... a result of drilling a phase 2 or phase 3 ultra-deep well? 203.30 Section 203.30 Mineral Resources... for royalty relief as a result of drilling a phase 2 or phase 3 ultra-deep well? Your lease may... longitude in water depths entirely less than 400 meters deep. (b) The lease has not produced gas or oil...

  5. 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?...

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. Critical behavior of two-dimensional models with spatially modulated phases: Analytic results

    NASA Astrophysics Data System (ADS)

    Ruján, P.

    1981-12-01

    The two-dimensional Elliott [or axial next-nearest-neighbor Ising (ANNNI)] model is mapped into an eight-vertex model with direct and staggered fields. With the use of the transfer-matrix approach it is shown that the dual of the ANNNI model belongs to the universality class of the one-dimensional quantum XY model in a staggered field at T=0. The phase structure is investigated by high- and low-temperature expansions of the correlation length and by spin-wave-like approximations valid in first order at low and high temperatures, respectively. The fact that the phase diagram obtained at low temperatures agrees qualitatively with recent results by Villain and Bak and by Coppersmith et al. shows that the paramagnetic phase extends until T=0. The role of the umklapp scattering in determining the critical wave vector in the modulated phase and in stabilizing the <2> antiphase is pointed out. In the eight-vertex representation the critical indices are identified in the floating, massless phase. The dislocations destabilizing this incommensurate phase correspond to the energy operator of the eight-vertex model. Finally, it is argued that the apparent contradiction between the low-temperature results on one hand, and the Monte Carlo simulations and high-temperature-expansion results on the other hand, is probably due to the strong oscillatory behavior of spin-spin correlation functions in the massive paramagnetic region.

  11. 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

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

    ClinicalTrials.gov

    2016-03-16

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  13. MRI and PET Imaging in Predicting Treatment Response in Patients With Stage IB-IVA Cervical Cancer

    ClinicalTrials.gov

    2016-06-24

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Cervical Undifferentiated Carcinoma; Recurrent Cervical Carcinoma; Stage IB2 Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  14. 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, 2010 CFR

    2010-07-01

    ... ROYALTY RATES OCS Oil, Gas, and Sulfur General Royalty Relief for Drilling Ultra-Deep Wells on Leases Not... a result of drilling a phase 2 or phase 3 ultra-deep well? 203.30 Section 203.30 Mineral Resources... drilling a phase 2 or phase 3 ultra-deep well? Your lease may receive a royalty suspension volume...

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

    ClinicalTrials.gov

    2016-10-28

    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. 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.

  17. 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.

  18. 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.

  19. 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

  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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. [3-phase scintigraphy in the Sudeck syndrome. Comparison with the results of roentgenologic and clinical studies].

    PubMed

    Koppers, B

    1982-11-01

    37 patients with clinically and radiologically proved reflex sympathetic dystrophy syndrome were scintigraphed by 99mTc-MDP (three-phase-scintigraphy). In 87% of the examinations (all three-phases) an increased tracer accumulation in the region of the affected limb could be seen scintigraphically. The majority of the positive results (92% resp. 87%) were found in the interval phase (phase II) and the late phase (phase III) of the scintigraphic examinations.--We recommend a staging of the increase of the tracer accumulation when examining the reflex sympathetic dystrophy syndrome. This staging doesn't significantly correlate with the familiar clinical and radiological stagings. However it may be useful when assessing the course of the syndrome.--Increased tracer accumulations could be observed in the case of clinically, radiologically and scintigraphically manifest reflex sympathetic dystrophy syndrome in the region of the foot, frequently in the ipsilateral knee region, rarely in the ipsilateral hip joint region, although clinically the syndrome could not be observed in these regions. PMID:6184293

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

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

    PubMed

    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

  13. 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.

  14. 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.

  15. Results of the Boeing/DOE DECC Phase 1 stirling engine project

    SciTech Connect

    STONE,KENNETH W.; CLARK,TERRY; NELVING,HANS; DIVER JR.,RICHARD B.

    2000-03-02

    Phase I of Boeing Company/DOE Dish Engine Critical Component (DECC) Project started in April of 1998 and was completed in 1999. The Phase I objectives, schedule, and test results are presented in this paper. These data shows the power, energy, and mirror performance are comparable to that when the hardware was first manufactured 15 years ago. During the Phase I and initial Phase II test period the on-sun system accumulated over 3,800 hours of solar-powered operating time, accumulated over 4,500 hours of concentrator solar tracking time, and generated over 50,000 kWh of grid-compatible electrical energy. The data also shows that the system was available 95 {percent} of the time when the sun's insolation level was above approximately 300 w/m{sup 2}, and achieved a daily energy efficiency between 20{percent} and 26{percent}. A second concentrator was refurbished during Phase I and accumulated over 2,200 hours of solar track time. A second Stirling engine operated 24 hours a day in a test cell in Sweden and accumulated over 6,000 test hours. Discussion of daily operation shows no major problems encountered during the testing that would prevent commercialization of the technology. Further analysis of the test data shows that system servicing with hydrogen, coolant and lubricating oil should not be a major O and M cost.

  16. 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

  17. The anaerobic corrosion of carbon steel in alkaline media - Phase 2 results

    NASA Astrophysics Data System (ADS)

    Smart, N. R.; Rance, A. P.; Fennell, P. A. H.; Kursten, B.

    2013-07-01

    In the Belgian Supercontainer concept a carbon steel overpack will surround high-level waste and spent fuel containers and be encased in a cementitious buffer material. A programme of research was carried out to investigate and measure the rate of anaerobic corrosion of carbon steel in an artificial alkaline porewater that simulates the aqueous phase in the cementitious buffer material. The corrosion rates were measured by monitoring hydrogen evolution using a manometric gas cell technique and by applying electrochemical methods. Phase 2 of the programme has repeated and extended previous Phase 1 measurements of the effects of radiation, temperature and chloride concentration of the anaerobic corrosion rate. This paper provides an update on the results from Phase 2 of the programme. The results confirm previous conclusions that the long-term corrosion rate of carbon steel in alkaline simulated porewater is determined by the formation of a thin barrier layer and a thicker outer layer composed of magnetite. Anaerobic corrosion of steel in cement requires an external supply of water.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Moving formal methods into practice. Verifying the FTPP Scoreboard: Results, phase 1

    NASA Technical Reports Server (NTRS)

    Srivas, Mandayam; Bickford, Mark

    1992-01-01

    This report documents the Phase 1 results of an effort aimed at formally verifying a key hardware component, called Scoreboard, of a Fault-Tolerant Parallel Processor (FTPP) being built at Charles Stark Draper Laboratory (CSDL). The Scoreboard is part of the FTPP virtual bus that guarantees reliable communication between processors in the presence of Byzantine faults in the system. The Scoreboard implements a piece of control logic that approves and validates a message before it can be transmitted. The goal of Phase 1 was to lay the foundation of the Scoreboard verification. A formal specification of the functional requirements and a high-level hardware design for the Scoreboard were developed. The hardware design was based on a preliminary Scoreboard design developed at CSDL. A main correctness theorem, from which the functional requirements can be established as corollaries, was proved for the Scoreboard design. The goal of Phase 2 is to verify the final detailed design of Scoreboard. This task is being conducted as part of a NASA-sponsored effort to explore integration of formal methods in the development cycle of current fault-tolerant architectures being built in the aerospace industry.

  5. High Rate User Ka-Band Phased Array Antenna Test Results

    NASA Technical Reports Server (NTRS)

    Caroglanian, Armen; Perko, Kenneth; Seufert, Steve; Dod, Tom; Warshowsky, Jay; Day, John H. (Technical Monitor)

    2001-01-01

    The High Rate User Phased Array Antenna (HRUPAA) is a Ka-Band planar phased array designed by the Harris Corporation for the NASA Goddard Space Flight Center. The HRUPAA permits a satellite to downlink data either to a ground station or through the Tracking and Data Relay Satellite System (TDRSS). The HRUPAA is scanned electronically by ground station / user satellite command over a 120 degree cone angle. The phased array has the advantage of not imparting attitude disturbances to the user spacecraft. The 288-element transmit-only array has distributed RF amplifiers integrated behind each of the printed patch antenna elements. The array has 33 dBW EIRP and is left-hand circularly polarized. An engineering model of a partially populated array has been developed and delivered to NASA Goddard Space Flight Center. This report deals with the testing of the engineering model at the Goddard Antenna Range near-field and compact range facilities. The antenna specifications are described first, followed by the test plan and test results.

  6. Mitigation of Tank 241-SY-101 by pump mixing: Results of testing phases A and B

    SciTech Connect

    Allemann, R.T.; Antoniak, Z.I.; Chvala, W.D.; Friley, J.R.; Gregory, W.B.; Hudson, J.D.; Michener, T.E.; Panisko, F.E.; Stewart, C.W.; Wise, B.M.; Efferding, L.E.; Fadeff, J.G.; Irwin, J.J.; Kirch, N.W.

    1994-03-01

    A spare mixing pump from the Hanford Grout Program was installed in Hanford double-shell waste Tank 241-SY-101 on July 3, 1993, after being modified to take advantage of waste stratification. It was anticipated that pump mixing would prevent large episodic flammable gas releases that had been occurring about every 100-150 days. A cautious initial test plan, called Phase A, was run to find how the pump and tank would behave in response to very brief and gentle pump operation. No large gas releases were triggered, and the pump performed well except for two incidents of nozzle plugging. On October 21, 1993, the next test series, Phase B, began, and the pump was applied more aggressively to mix the tank contents and mitigate uncontrolled gas releases. Orienting the pump in new directions released large volumes of gas and reduced the waste level to a near-record low. Results of the entire period from pump installation to the end of Phase B on December 17, 1993, are presented in detail in this document. Though long-term effects require further evaluation, we conclude from these data that the jet mixer pump is an effective means of controlling flammable gas release and that it has met the success criteria for mitigation in this tank.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. The liver toxicity biomarker study: phase I design and preliminary results.

    PubMed

    McBurney, Robert N; Hines, Wade M; Von Tungeln, Linda S; Schnackenberg, Laura K; Beger, Richard D; Moland, Carrie L; Han, Tao; Fuscoe, James C; Chang, Ching-Wei; Chen, James J; Su, Zhenqiang; Fan, Xiao-Hui; Tong, Weida; Booth, Shelagh A; Balasubramanian, Raji; Courchesne, Paul L; Campbell, Jennifer M; Graber, Armin; Guo, Yu; Juhasz, Peter J; Li, Tricin Y; Lynch, Moira D; Morel, Nicole M; Plasterer, Thomas N; Takach, Edward J; Zeng, Chenhui; Beland, Frederick A

    2009-01-01

    Drug-induced liver injury (DILI) is the primary adverse event that results in withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in development. The Liver Toxicity Biomarker Study (LTBS) is an innovative approach to investigate DILI because it compares molecular events produced in vivo by compound pairs that (a) are similar in structure and mechanism of action, (b) are associated with few or no signs of liver toxicity in preclinical studies, and (c) show marked differences in hepatotoxic potential. The LTBS is a collaborative preclinical research effort in molecular systems toxicology between the National Center for Toxicological Research and BG Medicine, Inc., and is supported by seven pharmaceutical companies and three technology providers. In phase I of the LTBS, entacapone and tolcapone were studied in rats to provide results and information that will form the foundation for the design and implementation of phase II. Molecular analysis of the rat liver and plasma samples combined with statistical analyses of the resulting datasets yielded marker analytes, illustrating the value of the broad-spectrum, molecular systems analysis approach to studying pharmacological or toxicological effects.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. Phase-space analysis and experimental results for secondary focusing at X-ray beamlines

    SciTech Connect

    Huang, Rong; Meron, Mati; Kujala, Naresh; Barrea, Raul A.

    2011-11-17

    Micro-focusing optical devices at synchrotron beamlines usually have a limited acceptance, but more flux can be intercepted if such optics are used to focus secondary sources created by the primary optics. Flux throughput can be maximized by placing the secondary focusing optics close to or exactly at the secondary source position. However, standard methods of beamline optics analysis, such as the lens equation or matching the mirror surface to an ellipse, work poorly when the source-to-optics distance is very short. In this paper the general characteristics of the focusing of beams with Gaussian profiles by a 'thin lens' are analysed under the paraxial approximation in phase space, concluding that the focusing of a beam with a short source-to-optics distance is distinct from imaging the source; slope errors are successfully included in all the formulas so that they can be used to calculate beamline focusing with good accuracy. A method is also introduced to use the thin-lens result to analyse the micro-focusing produced by an elliptically bent trapezoid-shaped Kirkpatrick-Baez mirror. The results of this analysis are in good agreement with ray-tracing simulations and are confirmed by the experimental results of the secondary focusing at the 18-ID Bio-CAT beamline (at the APS). The result of secondary focusing carried out at 18-ID using a single-bounce capillary can also be explained using this phase-space analysis. A discussion of the secondary focusing results is presented at the end of this paper.

  18. 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.

  19. CANARY phase B: on-sky open-loop tomographic LGS AO results

    NASA Astrophysics Data System (ADS)

    Morris, Tim; Gendron, Eric; Basden, Alastair; Martin, Olivier; Osborn, James; Henry, David; Hubert, Zoltan; Sivo, Gaetano; Gratadour, Damien; Chemla, Fanny; Sevin, Arnaud; Cohen, Matthieu; Younger, Eddy; Vidal, Fabrice; Wilson, Richard; Butterley, Tim; Bitenc, Urban; Reeves, Andrew; Bharmal, Nazim; Raynaud, Henri-François; Kulcsar, Caroline; Conan, Jean-Marc; Huet, Jean-Michel; Perret, Denis; Dickson, Colin; Atkinson, David; Bailie, Tom; Longmore, Andy; Todd, Stephen; Talbot, Gordon; Morris, Simon; Rousset, Gérard; Myers, Richard

    2014-07-01

    CANARY is an on-sky Laser Guide Star (LGS) tomographic AO demonstrator that has been in operation at the 4.2m William Herschel Telescope (WHT) in La Palma since 2010. In 2013, CANARY was upgraded from its initial configuration that used three off-axis Natural Guide Stars (NGS) through the inclusion of four off-axis Rayleigh LGS and associated wavefront sensing system. Here we present the system and analysis of the on-sky results obtained at the WHT between May and September 2014. Finally we present results from the final `Phase C' CANARY system that aims to recreate the tomographic configuration to emulate the expected tomographic AO configuration of both the AOF at the VLT and E-ELT.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Artemis common lunar lander. Phase 2: Study results for external review

    NASA Astrophysics Data System (ADS)

    1992-03-01

    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.

  13. Population Heterogeneity of Salmonella enterica Serotype Typhimurium Resulting from Phase Variation of the lpf Operon In Vitro and In Vivo

    PubMed Central

    Kingsley, Robert A.; Weening, Eric H.; Keestra, A. Marijke; Bäumler, Andreas J.

    2002-01-01

    The lpf fimbrial operon oscillates between phase ON and phase OFF expression states, thereby generating heterogeneity within S. enterica serotype Typhimurium populations with regard to expression of long polar fimbrial antigens. To determine whether the proportion of lpf phase variants changes with growth conditions, the lpf phase ON content of cultures was determined after in vitro and in vivo passage. After passage in Luria-Bertani (LB) broth for 120 generations, 96% of cells in a serotype Typhimurium culture carried the lpf operon in the phase ON expression state, regardless of the phase ON/OFF ratio in the inoculum. In contrast, a culture passaged on LB agar plates for 500 generations contained approximately 2% lpf phase ON cells. Differences in the lpf phase ON content of cultures passaged in broth and on plates were not caused by an outgrowth of lpf phase ON or lpf phase OFF cells, since deletion of lpf biosynthesis genes did not alter the phase ON/OFF ratio attained after passage. Instead, growth in LB broth resulted in a eightfold increase in the phase OFF-to-ON transition frequency and a decrease of the lpf phase ON-to-OFF transition frequency by a factor of 150 compared to growth on LB agar plates. After infection of naïve CBA/J mice with an lpf phase ON culture of serotype Typhimurium, the proportion of lpf phase ON cells continuously decreased over time, regardless of whether the strain carried intact fimbrial biosynthesis genes. These data suggest that elaboration of fimbriae does not have a major influence on the population heterogeneity produced by phase variation of the lpf operon in naïve mice. PMID:11948147

  14. Population heterogeneity of Salmonella enterica serotype Typhimurium resulting from phase variation of the lpf operon in vitro and in vivo.

    PubMed

    Kingsley, Robert A; Weening, Eric H; Keestra, A Marijke; Bäumler, Andreas J

    2002-05-01

    The lpf fimbrial operon oscillates between phase ON and phase OFF expression states, thereby generating heterogeneity within S. enterica serotype Typhimurium populations with regard to expression of long polar fimbrial antigens. To determine whether the proportion of lpf phase variants changes with growth conditions, the lpf phase ON content of cultures was determined after in vitro and in vivo passage. After passage in Luria-Bertani (LB) broth for 120 generations, 96% of cells in a serotype Typhimurium culture carried the lpf operon in the phase ON expression state, regardless of the phase ON/OFF ratio in the inoculum. In contrast, a culture passaged on LB agar plates for 500 generations contained approximately 2% lpf phase ON cells. Differences in the lpf phase ON content of cultures passaged in broth and on plates were not caused by an outgrowth of lpf phase ON or lpf phase OFF cells, since deletion of lpf biosynthesis genes did not alter the phase ON/OFF ratio attained after passage. Instead, growth in LB broth resulted in a eightfold increase in the phase OFF-to-ON transition frequency and a decrease of the lpf phase ON-to-OFF transition frequency by a factor of 150 compared to growth on LB agar plates. After infection of naïve CBA/J mice with an lpf phase ON culture of serotype Typhimurium, the proportion of lpf phase ON cells continuously decreased over time, regardless of whether the strain carried intact fimbrial biosynthesis genes. These data suggest that elaboration of fimbriae does not have a major influence on the population heterogeneity produced by phase variation of the lpf operon in naïve mice. PMID:11948147

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Oscillatory phase modulates the timing of neuronal activations and resulting behavior.

    PubMed

    Coon, W G; Gunduz, A; Brunner, P; Ritaccio, A L; Pesaran, B; Schalk, G

    2016-06-01

    Human behavioral response timing is highly variable from trial to trial. While it is generally understood that behavioral variability must be due to trial-by-trial variations in brain function, it is still largely unknown which physiological mechanisms govern the timing of neural activity as it travels through networks of neuronal populations, and how variations in the timing of neural activity relate to variations in the timing of behavior. In our study, we submitted recordings from the cortical surface to novel analytic techniques to chart the trajectory of neuronal population activity across the human cortex in single trials, and found joint modulation of the timing of this activity and of consequent behavior by neuronal oscillations in the alpha band (8-12Hz). Specifically, we established that the onset of population activity tends to occur during the trough of oscillatory activity, and that deviations from this preferred relationship are related to changes in the timing of population activity and the speed of the resulting behavioral response. These results indicate that neuronal activity incurs variable delays as it propagates across neuronal populations, and that the duration of each delay is a function of the instantaneous phase of oscillatory activity. We conclude that the results presented in this paper are supportive of a general model for variability in the effective speed of information transmission in the human brain and for variability in the timing of human behavior. PMID:26975551

  20. Promising short-term clinical results of the cementless Oxford phase III medial unicondylar knee prosthesis

    PubMed Central

    van Dorp, Karin B; Breugem, Stefan JM; Bruijn, Daniël J; Driessen, Marcel JM

    2016-01-01

    AIM: To investigate the short-term clinical results of the Oxford phase III cementless medial unicondylar knee prosthesis (UKP) compared to the cemented medial UKP. METHODS: 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. RESULTS: 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. CONCLUSION: The cementless Oxford phase III medial UKP shows good short-term clinical results, when used in a specialist clinic by an experienced surgeon. PMID:27114932

  1. 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.

  2. 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.

  3. In situ permeable flow sensors at the Savannah River Integrated Demonstration: Phase 1 results

    SciTech Connect

    Ballard, S.

    1992-10-01

    The In Situ Permeable Flow Sensor, a new technology which uses a thermal perturbation technique to directly measure the 3-dimensional groundwater flow velocity vector at a point in permeable, unconsolidated geologic formations, has been used to monitor changes in the groundwater flow regime around an experimental air stripping waste remediation activity. While design flaws in the first version of the technology, which were used during the experiment being reported here, precluded measurements of the horizontal component of the flow velocity, measurements of the vertical component of the flow velocity were obtained. Results indicate that significant changes in the vertical flow velocity were induced by the air injection system. One flow sensor, MHM6, measured a vertical flow velocity of 4 m/yr or less when the air injection system was not operating and 25 m/yr when the air injection system was on. This may be caused by air bubbles moving past the probes or may be the result of the establishment of a more widespread flow regime in the groundwater induced by the air injection system. In the latter case, significantly more groundwater would be remediated by the air stripping operation since groundwater would be circulated through the zone of influence of the air injection system. Newly designed flow sensors, already in the ground at Savannah River to monitor Phase II of the project, are capable of measuring horizontal as well as vertical components of flow velocity.

  4. 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.

  5. 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

    2016-01-01

    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. PMID:27323085

  6. 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.

  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. Chikusetsu saponin IVa confers cardioprotection via SIRT1/ERK1/2 and Homer1a pathway.

    PubMed

    Duan, Jialin; Yin, Ying; Wei, Guo; Cui, Jia; Zhang, Enhu; Guan, Yue; Yan, Jiajia; Guo, Chao; Zhu, Yanrong; Mu, Fei; Weng, Yan; Wang, Yanhua; Wu, Xiaoxiao; Xi, Miaomiao; Wen, Aidong

    2015-01-01

    Hyperglycemia-induced reactive oxygen species (ROS) generation and Ca(2+) overload contribute to the development of diabetic cardiomyopathy. In this study, we aimed to study the protective effects of Chikusetsu saponin IVa (CHS) from Aralia taibaiensis against hyperglycemia-induced myocardial injuries. Treatment of H9c2 cells with high glucose (HG) for 24 h resulted in a loss of cell viability and increase of ROS, LDH and Ca(2+) levels, and also induced cell apoptosis, and those changes were all markedly reversed by the administration of CHS. In further studies, CHS dose-dependently increased the expression of Homer1a, ERK1/2 and SIRT1 in both H9c2 cells and rat primary cardiomyocytes. However, transfection of Homer1a-specific siRNA abolished the ability of CHS in controlling the ROS and Ca(2+) homeostasis. Moreover, specific SIRT1 inhibitors or siRNA significantly suppressed the enhanced phosphorylation of ERK1/2 and expression of Homer1a induced by CHS as well as its cytoprotective effect. CHS induced Homer1a expression was also suppressed by siERK1/2. Additionally, results in diabetic mice also showed that CHS protected myocardium from I/R-introduced apoptosis by activating the SIRT1/ERK1/2/Homer1a pathway. These results demonstrated that CHS protected against hyperglycemia-induced myocardial injury through SIRT1/ERK1/2 and Homer1a pathway in vivo and in vitro. PMID:26648253

  10. 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.

  11. 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

  12. Solid-liquid phase boundaries of lens protein solutions.

    PubMed Central

    Berland, C R; Thurston, G M; Kondo, M; Broide, M L; Pande, J; Ogun, O; Benedek, G B

    1992-01-01

    We report measurement of the solid-liquid phase boundary, or liquidus line, for aqueous solutions of three pure calf gamma-crystallin proteins: gamma II, gamma IIIa, and gamma IIIb. We also studied the liquidus line for solutions of native gamma IV-crystallin calf lens protein, which consists of 85% gamma IVa/15% gamma IVb. In all four proteins the liquidus phase boundaries lie higher in temperature than the previously determined liquid-liquid coexistence curves. Thus, over the range of concentration and temperature for which liquid-liquid phase separation occurs, the coexistence of a protein crystal phase with a protein liquid solution phase is thermodynamically stable relative to the metastable separated liquid phases. The location of the liquidus lines clearly divides these four crystallin proteins into two groups: those in which liquidus lines flatten at temperatures greater than 70 degrees C: gamma IIIa and gamma IV, and those in which liquidus lines flatten at temperatures less than 50 degrees C: gamma II and gamma IIIb. We have analyzed the form of the liquidus lines by using specific choices for the structures of the Gibbs free energy in solution and solid phases. By applying the thermodynamic conditions for equilibrium between the two phases to the resulting chemical potentials, we can estimate the temperature-dependent free energy change upon binding of protein and water into the solid phase. PMID:1741375

  13. 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, 2012 CFR

    2012-07-01

    ... a result of drilling a phase 2 or phase 3 ultra-deep well? 203.30 Section 203.30 Mineral Resources... RELIEF OR REDUCTION IN ROYALTY RATES OCS Oil, Gas, and Sulfur General § 203.30 Which leases are eligible... receive a royalty suspension volume (RSV) under §§ 203.31 through 203.36 if the lease meets all...

  14. 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, 2013 CFR

    2013-07-01

    ... a result of drilling a phase 2 or phase 3 ultra-deep well? 203.30 Section 203.30 Mineral Resources... RELIEF OR REDUCTION IN ROYALTY RATES OCS Oil, Gas, and Sulfur General § 203.30 Which leases are eligible... receive a royalty suspension volume (RSV) under §§ 203.31 through 203.36 if the lease meets all...

  15. 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.

  16. 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.; Irvine, Peter; Jones, Andrew; Lawrence, M. G.; Maccracken, Michael C.; Muri, Helene O.; Moore, John; Niemeier, Ulrike; Phipps, Steven; 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 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.

  17. Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results.

    PubMed Central

    Waugh, W. H.; Daeschner, C. W.; Files, B. A.; McConnell, M. E.; Strandjord, S. E.

    2001-01-01

    L-Arginine may be a conditionally essential amino acid in children and adolescents with sickle cell disease, particularly as required substrate in the arginine-nitric oxide pathway for endogenous nitrovasodilation and vasoprotection. Vasoprotection by arginine is mediated partly by nitric oxide-induced inhibition of endothelial damage and inhibition of adhesion and activation of leukocytes. Activated leukocytes may trigger many of the complications, including vasoocclusive events and intimal hyperplasias. High blood leukocyte counts during steady states in the absence of infection are significant laboratory risk factors for adverse complications. L-Citrulline as precursor amino acid was given orally twice daily in daily doses of approximately 0.1 g/kg in a pilot Phase II clinical trial during steady states in four homozygous sickle cell disease subjects and one sickle cell-hemoglobin C disease patient (ages 10-18). There soon resulted dramatic improvements in symptoms of well-being, raised plasma arginine levels, and reductions in high total leukocyte and high segmented neutrophil counts toward or to within normal limits. Continued L-citrulline supplementation in compliant subjects continued to lessen symptomatology, to maintain plasma arginine concentrations greater than control levels, and to maintain nearly normal total leukocyte and neutrophil counts. Side effects or toxicity from citrulline were not experienced. Oral L-citrulline may portend very useful for palliative therapy in sickle cell disease. Placebo-controlled, long-term trials are now indicated. PMID:11688916

  18. The Geoengineering Model Intercomparison Project Phase 6 (GeoMIP6): Simulation design and preliminary results

    DOE PAGES

    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.; et al

    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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  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. 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.

  6. A neon-E rich phase in Orgueil - Results of stepwise heating experiments

    NASA Technical Reports Server (NTRS)

    Eberhardt, P.

    1978-01-01

    A Ne-E rich phase was separated from the Orgeuil carbonaceous chondrite. He and Ne were analyzed in this phase and in an Orgueil residual bulk silicate sample using the stepwise heating technique. Ne-E was found to be released from the Ne-E rich phase at temperatures as low as 500 C; however, gas richest in Ne-E is observed at the highest temperatures (1230 C). The following limits for the isotopic composition of Ne-E were obtained: Ne-20/Ne-22 less than 1.52; Ne-21/Ne-22 less than 0.0244.

  7. Ten- to 15-year results of the Oxford Phase III mobile unicompartmental knee arthroplasty

    PubMed Central

    Lisowski, L. A.; Meijer, L. I.; van den Bekerom, M. P. J.; Pilot, P.; Lisowski, A. E.

    2016-01-01

    Aims The interest in unicompartmental knee arthroplasty (UKA) for medial osteoarthritis has increased rapidly but the long-term follow-up of the Oxford UKAs has yet to be analysed in non-designer centres. We have examined our ten- to 15-year clinical and radiological follow-up data for the Oxford Phase III UKAs. Patients and Methods Between January 1999 and January 2005 a total of 138 consecutive Oxford Phase III arthroplasties were performed by a single surgeon in 129 patients for medial compartment osteoarthritis (71 right and 67 left knees, mean age 72.0 years (47 to 91), mean body mass index 28.2 (20.7 to 52.2)). Both clinical data and radiographs were prospectively recorded and obtained at intervals. Of the 129 patients, 32 patients (32 knees) died, ten patients (12 knees) were not able to take part in the final clinical and radiological assessment due to physical and mental conditions, but via telephone interview it was confirmed that none of these ten patients (12 knees) had a revision of the knee arthroplasty. One patient (two knees) was lost to follow-up. Results The mean follow-up was 11.7 years (10 to 15). A total of 11 knees (8%) were revised. The survival at 15 years with revision for any reason as the endpoint was 90.6% (95% confidence interval (CI) 85.2 to 96.0) and revision related to the prosthesis was 99.3% (95% CI 97.9 to 100). The mean total Knee Society Score was 47 (0 to 80) pre-operatively and 81 (30 to 100) at latest follow-up. The mean Oxford Knee Score was 19 (12 to 40) pre-operatively and 42 (28 to 55) at final follow-up. Radiolucency beneath the tibial component occurred in 22 of 81 prostheses (27.2%) without evidence of loosening. Conclusion This study supports the use of UKA in medial compartment osteoarthritis with excellent long-term functional and radiological outcomes with an excellent 15-year survival rate. Cite this article: Bone Joint J 2016;98-B(10 Suppl B):41–7. PMID:27694515

  8. 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.

  9. PilN Binding Modulates the Structure and Binding Partners of the Pseudomonas aeruginosa Type IVa Pilus Protein PilM.

    PubMed

    McCallum, Matthew; Tammam, Stephanie; Little, Dustin J; Robinson, Howard; Koo, Jason; Shah, Megha; Calmettes, Charles; Moraes, Trevor F; Burrows, Lori L; Howell, P Lynne

    2016-05-20

    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. We propose a working model in which dynamic binding of PilN facilitates functionally relevant structural changes in PilM.

  10. 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

  11. 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.

  12. 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.

  13. Results of two-dimensional time-evolved phase screen computer simulations

    NASA Astrophysics Data System (ADS)

    Gamble, Kevin J.; Weeks, Arthur R.; Myler, Harley R.; Rabadi, Wissam A.

    1995-06-01

    This paper presents a 2D computer simulation of observed intensity and phase behind a time evolved phase screen. Both spatial and temporal statistics of the observed intensity is compared to theoretical predictions. In particular, the intensity statistics as a function of detector position within the propagated laser beam are investigated. The computer simulation program was written using the C-programming language running on a SUN SPARC-5 workstation.

  14. 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

  15. Lead decline in the Indian environment resulting from the petrol-lead phase-out programme.

    PubMed

    Singh, Amit Kumar; Singh, Munendra

    2006-09-15

    Recently, the lead content of various environmental components has decreased in response to replacement of leaded petrol by unleaded petrol. In India, 15 research studies are here assessed with respect to lead concentrations in various environmental components during the leaded petrol phase (before 1996), the transitional phase (1996-2000) and the unleaded petrol phase (2000 onwards). The Ganga River Water exhibited a decrease in lead concentration from 18.0 microg/l in 1988 to 3.1 microg/l in 2001. In Lucknow urban centre, mean lead concentrations in the urban air decreased from 1.6 microg/m(3) in 1994 to 0.2 microg/m(3) in 2002. Lead concentrations in Dalbergia sissoo tree leaves also decreased from 18.7 microg/g dry wt. in 1994 to 8.3 microg/g dry wt. in 2004. Mean blood-lead levels of children from Mumbai, Chennai, Bangalore, Amritsar and Lucknow urban centres have fallen from 18.1 microg/dl in the leaded petrol phase to 12.1 microg/dl in the unleaded petrol phase. The petrol-lead phase-out effort in India has reduced lead concentrations in the various environmental components after 2000. It will help to reduce the exposure of millions of people to environmental lead. PMID:16764909

  16. Cabozantinib in Patients With Advanced Prostate Cancer: Results of a Phase II Randomized Discontinuation Trial

    PubMed Central

    Smith, David C.; Smith, Matthew R.; Sweeney, Christopher; Elfiky, Aymen A.; Logothetis, Christopher; Corn, Paul G.; Vogelzang, Nicholas J.; Small, Eric J.; Harzstark, Andrea L.; Gordon, Michael S.; Vaishampayan, Ulka N.; Haas, Naomi B.; Spira, Alexander I.; Lara, Primo N.; Lin, Chia-Chi; Srinivas, Sandy; Sella, Avishay; Schöffski, Patrick; Scheffold, Christian; Weitzman, Aaron L.; Hussain, Maha

    2013-01-01

    Purpose Cabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2. We evaluated the activity of cabozantinib in patients with castration-resistant prostate cancer (CRPC) in a phase II randomized discontinuation trial with an expansion cohort. Patients and Methods Patients received 100 mg of cabozantinib daily. Those with stable disease per RECIST at 12 weeks were randomly assigned to cabozantinib or placebo. Primary end points were objective response rate at 12 weeks and progression-free survival (PFS) after random assignment. Results One hundred seventy-one men with CRPC were enrolled. Random assignment was halted early based on the observed activity of cabozantinib. Seventy-two percent of patients had regression in soft tissue lesions, whereas 68% of evaluable patients had improvement on bone scan, including complete resolution in 12%. The objective response rate at 12 weeks was 5%, with stable disease in 75% of patients. Thirty-one patients with stable disease at week 12 were randomly assigned. Median PFS was 23.9 weeks (95% CI, 10.7 to 62.4 weeks) with cabozantinib and 5.9 weeks (95% CI, 5.4 to 6.6 weeks) with placebo (hazard ratio, 0.12; P < .001). Serum total alkaline phosphatase and plasma cross-linked C-terminal telopeptide of type I collagen were reduced by ≥ 50% in 57% of evaluable patients. On retrospective review, bone pain improved in 67% of evaluable patients, with a decrease in narcotic use in 56%. The most common grade 3 adverse events were fatigue (16%), hypertension (12%), and hand-foot syndrome (8%). Conclusion Cabozantinib has clinical activity in men with CRPC, including reduction of soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use. PMID:23169517

  17. 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.

  18. 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.

  19. The North American Regional Climate Change Assessment Program (NARCCAP): Overview of Phase II Results

    NASA Astrophysics Data System (ADS)

    Mearns, L. O.

    2008-12-01

    NARCCAP is an international program that serves the climate scenario needs of the United States, Canada, and northern Mexico. We are systematically investigating the uncertainties in regional scale projections of future climate and producing high resolution climate change scenarios using multiple regional climate models(RCMs)and multiple global model responses to a future emission scenario, by nesting the RCMs within atmosphere ocean general circulation models (AOGCMs) forced with the A2 SRES scenario, over a domain covering the conterminous US, northern Mexico, and most of Canada. The project also includes a validation component through nesting the participating RCMs within NCEP reanalyses. The basic spatial resolution of the RCM simulations is 50 km. This program includes RCMs that participated in the European PRUDENCE program (HadRM3 and RegCM), the Canadian regional climate model (CRCM) as well as the NCEP regional spectral model (RSM), the NCAR/PSU MM5, and NCAR WRF. AOGCMs include the Hadley Centre HadCM3, NCAR CCSM3, the Canadian CGCM3 and the GFDL model. The resulting climate model runs form the basis for multiple high resolution climate scenarios that can be used in climate change impacts assessments over North America. High resolution (50 km) global time-slice experiments based on the GFDL atmospheric model (AM2.1) and the NCAR atmospheric model (CAM3) have also been produced and will be compared with the simulations of the regional models. There also will be opportunities for double nesting over key regions through which additional modelers in the regional modeling community will be able to participate in NARCCAP. Additional key science issues are being investigated such as the importance of compatible physics in the nested and nesting models. Measures of uncertainty across the multiple runs are being developed by geophysical statisticians. In this overview talk, results from Phase II of the project, the RCM simulations using boundary conditions from the

  20. Magnetic Resonance–Guided Focused Ultrasound for Patients With Painful Bone Metastases: Phase III Trial Results

    PubMed Central

    Ghanouni, Pejman; Kanaev, Sergey V.; Iozeffi, Dmitri; Gianfelice, David; Fennessy, Fiona Mary; Kuten, Abraham; Meyer, Joshua E.; LeBlang, Suzanne D.; Roberts, Ann; Choi, Junsung; Larner, James M.; Napoli, Alessandro; Turkevich, Vladimir G.; Inbar, Yael; Tempany, Clare Mary C.; Pfeffer, Raphael M.

    2014-01-01

    Background Pain due to bone metastases is a common cause of cancer-related morbidity, with few options available for patients refractory to medical therapies and who do not respond to radiation therapy. This study assessed the safety and efficacy of magnetic resonance-guided focused ultrasound surgery (MRgFUS), a noninvasive method of thermal tissue ablation for palliation of pain due to bone metastases. Methods Patients with painful bone metastases were randomly assigned 3:1 to receive MRgFUS sonication or placebo. The primary endpoint was improvement in self-reported pain score without increase of pain medication 3 months after treatment and was analyzed by Fisher’s exact test. Components of the response composite, Numerical Rating Scale for pain (NRS) and morphine equivalent daily dose intake, were analyzed by t test and Wilcoxon rank-sum test, respectively. Brief Pain Inventory (BPI-QoL), a measure of functional interference of pain on quality of life, was compared between MRgFUS and placebo by t test. Statistical tests were two-sided. Results One hundred forty-seven subjects were enrolled, with 112 and 35 randomly assigned to MRgFUS and placebo treatments, respectively. Response rate for the primary endpoint was 64.3% in the MRgFUS arm and 20.0% in the placebo arm (P < .001). MRgFUS was also superior to placebo at 3 months on the secondary endpoints assessing worst score NRS (P < .001) and the BPI-QoL (P < .001). The most common treatment-related adverse event (AE) was sonication pain, which occurred in 32.1% of MRgFUS patients. Two patients had pathological fractures, one patient had third-degree skin burn, and one patient suffered from neuropathy. Overall 60.3% of all AEs resolved on the treatment day. Conclusions This multicenter phase III trial demonstrated that MRgFUS is a safe and effective, noninvasive treatment for alleviating pain resulting from bone metastases in patients that have failed standard treatments. PMID:24760791

  1. 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

  2. Glycoprotein and Glycan in Tissue and Blood Samples of Patients With Stage IB-IVA Cervical Cancer Undergoing Surgery to Remove Pelvic and Abdominal Lymph Nodes

    ClinicalTrials.gov

    2016-10-26

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

  3. 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.

  4. 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

  5. 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

  6. Negative results in phase III trials of complex interventions: cause for concern or just good science?

    PubMed

    Crawford, Mike J; Barnicot, Kirsten; Patterson, Sue; Gold, Christian

    2016-07-01

    Not all interventions that show promise in exploratory trials will be supported in phase III studies. But the high failure rate in recent trials of complex mental health interventions is a concern. Proper consideration of trial processes and greater use of adaptive trial designs could ensure better use of available resources. PMID:27369475

  7. Income Verification Pilot Project (Phase II): Results of Quality Assurance Evaluation, 1982-83 School Year.

    ERIC Educational Resources Information Center

    Applied Management Sciences, Inc., Silver Spring, MD.

    Presented in this report are selected findings of the Income Verification Pilot Project (IVPP), an investigation examining misreporting of applicant income and family size on applications for government-sponsored school meal benefits. As reported here, Phase II of the project provided for a comprehensive assessment of specific quality assurance…

  8. 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.

  9. The second-order procedure: exact vs approximate results for isotropic, two-phase composites

    NASA Astrophysics Data System (ADS)

    Nebozhyn, M. V.; Castañeda, P. Ponte

    1999-10-01

    Estimates for the effective behavior of statistically isotropic, two-phase, nonlinear elastic (or viscous) composites were given by Ponte Castañeda (1996; J. Mech. Phys. Solids44, 827), making use of the 'second-order procedure', also introduced in that reference. The actual computation of these estimates took advantage of a simplifying hypothesis consisting of taking the average strain deviators in the phases to be proportional to the macroscopic strain deviator. In this paper, a more general analysis is presented that shows that while the 'proportional strain' hypothesis does hold for some special cases, it does not in general. In fact, the average strain deviators in the phases are found to be only co-axial with the macroscopic strain deviator. On the other hand, the proportional strain hypothesis, together with an approximate form of the relevant P tensor, is found to lead to fairly small errors, relative to the exact solution of the problem. The largest errors, which occur for large phase contrast and nonlinearity, are less than about two percent. Because of this, and given the significant simplifications achieved, the use of the proportional strain hypothesis and of the approximate form of the P tensor are recommended. Certainly, these approximations are much more accurate than the isotropic-type approximations that have been used in the past in the context of other homogenization procedures.

  10. 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...

  11. 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

  12. 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

  13. Use of the Remote Access Virtual Environment Network (RAVEN) for coordinated IVA-EVA astronaut training and evaluation.

    PubMed

    Cater, J P; Huffman, S D

    1995-01-01

    This paper presents a unique virtual reality training and assessment tool developed under a NASA grant, "Research in Human Factors Aspects of Enhanced Virtual Environments for Extravehicular Activity (EVA) Training and Simulation." The Remote Access Virtual Environment Network (RAVEN) was created to train and evaluate the verbal, mental and physical coordination required between the intravehicular (IVA) astronaut operating the Remote Manipulator System (RMS) arm and the EVA astronaut standing in foot restraints on the end of the RMS. The RAVEN system currently allows the EVA astronaut to approach the Hubble Space Telescope (HST) under control of the IVA astronaut and grasp, remove, and replace the Wide Field Planetary Camera drawer from its location in the HST. Two viewpoints, one stereoscopic and one monoscopic, were created all linked by Ethernet, that provided the two trainees with the appropriate training environments.

  14. Crystal structures of antibiotic-bound complexes of aminoglycoside 2''-phosphotransferase IVa highlight the diversity in substrate binding modes among aminoglycoside kinases.

    PubMed

    Shi, Kun; Houston, Douglas R; Berghuis, Albert M

    2011-07-19

    Aminoglycoside 2''-phosphotransferase IVa [APH(2'')-IVa] is a member of a family of bacterial enzymes responsible for medically relevant resistance to antibiotics. APH(2'')-IVa confers high-level resistance against several clinically used aminoglycoside antibiotics in various pathogenic Enterococcus species by phosphorylating the drug, thereby preventing it from binding to its ribosomal target and producing a bactericidal effect. We describe here three crystal structures of APH(2'')-IVa, one in its apo form and two in complex with a bound antibiotic, tobramycin and kanamycin A. The apo structure was refined to a resolution of 2.05 Å, and the APH(2'')-IVa structures with tobramycin and kanamycin A bound were refined to resolutions of 1.80 and 2.15 Å, respectively. Comparison among the structures provides insight concerning the substrate selectivity of this enzyme. In particular, conformational changes upon substrate binding, involving rotational shifts of two distinct segments of the enzyme, are observed. These substrate-induced shifts may also rationalize the altered substrate preference of APH(2'')-IVa in comparison to those of other members of the APH(2'') subfamily, which are structurally closely related. Finally, analysis of the interactions between the enzyme and aminoglycoside reveals a distinct binding mode as compared to the intended ribosomal target. The differences in the pattern of interactions can be utilized as a structural basis for the development of improved aminoglycosides that are not susceptible to these resistance factors.

  15. Alirocumab for hyperlipidemia: ODYSSEY Phase III clinical trial results and US FDA approval indications.

    PubMed

    Roth, Eli M

    2016-03-01

    A new class of lipid-lowering drugs, inhibitors of PCSK9 has been generating impressive clinical trial data over the last several years, and alirocumab (Praluent) has become the first to be approved by the US FDA. Alirocumab has been shown to lower low density lipoprotein cholesterol by 45-62% with a safety profile generally comparable to placebo. Alirocumab is a monoclonal antibody to PCSK9 administered subcutaneously and has been evaluated in 16 Phase III clinical trials, the majority of which have been enrolled or completed. This article will be a review of the available Phase III safety and efficacy data of the ODYSSEY studies including a brief description of each of the 16 studies. PMID:26785741

  16. Biochemical and structural analysis of missense mutations in N-acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes.

    PubMed

    Sukegawa, K; Nakamura, H; Kato, Z; Tomatsu, S; Montaño, A M; Fukao, T; Toietta, G; Tortora, P; Orii, T; Kondo, N

    2000-05-22

    Mucopolysaccharidosis IVA (MPS IVA; OMIM#253000), a lysosomal storage disorder caused by a deficiency of N -acetylgalactosamine-6-sulfate sulfatase (GALNS), has variable clinical phenotypes. To date we have identified 65 missense mutations in the GALNS gene from MPS IVA patients, but the correlation between genotype and phenotype has remained unclear. We studied 17 missense mutations using biochemical approaches and 32 missense mutations, using structural analyses. Fifteen missense mutations and two newly engineered active site mutations (C79S, C79T) were characterized by transient expression analysis. Mutant proteins, except for C79S and C79T, were destabilized and detected as insoluble precursor forms while the C79S and C79T mutants were of a soluble mature size. Mutants found in the severe phenotype had no activity. Mutants found in the mild phenotype had a considerable residual activity (1.3-13.3% of wild-type GALNS activity). Sulfatases, including GALNS, are members of a highly conserved gene family sharing an extensive sequence homology. Thus, a tertiary structural model of human GALNS was constructed from the X-ray crystal structure of N -acetylgalacto-samine-4-sulfatase and arylsulfatase A, using homology modeling, and 32 missense mutations were investigated. Consequently, we propose that there are at least three different reasons for the severe phenotype: (i) destruction of the hydrophobic core or modification of the packing; (ii) removal of a salt bridge to destabilize the entire conformation; (iii) modification of the active site. In contrast, mild mutations were mostly located on the surface of the GALNS protein. These studies shed further light on the genotype-phenotype correlation of MPS IVA and structure-function relationship in the sulfatase family. PMID:10814710

  17. Heteroallelic missense mutations of the galactosamine-6-sulfate sulfatase (GALNS) gene in a mild form of Morquio disease (MPS IVA)

    SciTech Connect

    Cole, D.E.C.; Gordon, B.A.; Rupar, C.A.

    1996-06-28

    Morquio disease (MPS IVA) is an autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity. Patients commonly present in early infancy with growth failure, spondyloepiphyseal dysplasia, corneal opacification, and keratan sulfaturia, but milder forms have been described. We report on a patient who grew normally until age 5 years. Her keratan sulfaturia was not detected until adolescence, and she now has changes restricted largely to the axial skeleton. She has experienced only mildly impaired vision. At age 22, thin-layer chromatography of purified glycosaminoglycans showed some keratan sulfaturia. GALNS activity in fibroblast homogenate supernatants was 20 {plus_minus} 5% of controls (as compared to 5 {plus_minus} 3% of controls in severe MPS IVA, P <.003). Kinetic analysis of residual fibroblast GALNS activity in patient and parents revealed decreased K{sub m} and increased V{sub max} in the mother and daughter, but not in the father, compatible with compound heterozygosity. GALNS exons were amplified from patient genomic DNA and screened by SSCP. Two missense mutations, a C to T transition at position 335 (predicting R94C) and a T to G transversion at position 344 (predicting F97V), were found on sequencing an abnormally migrating exon 3 amplicon. Digestion of the amplicon with FokI and AccI restriction enzymes (specific for the R94C and F97V mutations, respectively) confirmed heterozygosity. In fibroblast transfection experiments, heterozygous R94C and F97V mutants independently expressed as severe and mile GALNS deficiency, respectively. We interpret these findings to indicate that our patient bears heteroallelic GALNS missense mutations, leading to GALNS deficiency and mild MPS IVA. Our findings expand the clinical and biochemical phenotype of MPS IVA, but full delineation of the genotype-phenotype relationship requires further study of native and transfected mutant cell lines. 30 refs., 4 figs., 3 tabs.

  18. NEPHELINE FORMATION STUDY FOR SLUDGE BATCH 4: PHASE 3 EXPERIMENTAL RESULTS

    SciTech Connect

    Fox, K

    2006-05-01

    This Phase 3 study was undertaken to complement the previous phases of the nepheline formation studies1, 2 by continuing the investigation into the ability of the nepheline discriminator to predict the occurrence of nepheline crystallization in Sludge Batch 4 (SB4) glasses and into the impact of such phases on the durability of the SB4 glasses. The Phase 3 study had two primary objectives. The first was to continue to demonstrate the ability of the discriminator value to adequately predict the nepheline formation potential for specific glass systems of interest. The second was to generate additional data that have a high probability of supporting the SB4 variability study. To support these two objectives, sixteen glasses were selected based on the most recent SB4 compositional projection, Case 15C Blend 1.3 Four different frits were included, based on previous assessments of projected operating windows and melt rate,4, 5 with four WLs selected for each frit. Eight of these frit-sludge combinations covered WLs which tightly bound the nepheline discriminator value of 0.62, with the intent of refining this value to a level of confidence where it can be incorporated into offline administrative controls and/or the Process Composition Control System (PCCS) to support Slurry Mix Evaporator (SME) acceptability decisions. The remaining eight frit-sludge combinations targeted lower WLs (35 and 40%) and were prepared and analyzed to contribute needed data to the ComPro database6 to support a potential variability study for SB4.

  19. Thermodynamically Constrained Averaging Theory (TCAT) Two-Phase Flow Model: Derivation, Closure, and Simulation Results

    NASA Astrophysics Data System (ADS)

    Weigand, T. M.; Miller, C. T.; Dye, A. L.; Gray, W. G.; McClure, J. E.; Rybak, I.

    2015-12-01

    The thermodynamically constrained averaging theory (TCAT) has been usedto formulate general classes of porous medium models, including newmodels for two-fluid-phase flow. The TCAT approach provides advantagesthat include a firm connection between the microscale, or pore scale,and the macroscale; a thermodynamically consistent basis; explicitinclusion of factors such as interfacial areas, contact angles,interfacial tension, and curvatures; and dynamics of interface movementand relaxation to an equilibrium state. In order to render the TCATmodel solvable, certain closure relations are needed to relate fluidpressure, interfacial areas, curvatures, and relaxation rates. In thiswork, we formulate and solve a TCAT-based two-fluid-phase flow model. We detail the formulation of the model, which is a specific instancefrom a hierarchy of two-fluid-phase flow models that emerge from thetheory. We show the closure problem that must be solved. Using recentresults from high-resolution microscale simulations, we advance a set ofclosure relations that produce a closed model. Lastly, we solve the model using a locally conservative numerical scheme and compare the TCAT model to the traditional model.

  20. Inherited human group IVA cytosolic phospholipase A2 deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation

    PubMed Central

    Kirkby, Nicholas S.; Reed, Daniel M.; Edin, Matthew L.; Rauzi, Francesca; Mataragka, Stefania; Vojnovic, Ivana; Bishop-Bailey, David; Milne, Ginger L.; Longhurst, Hilary; Zeldin, Darryl C.; Mitchell, Jane A.; Warner, Timothy D.

    2016-01-01

    Eicosanoids are important vascular regulators, but the phospholipase A2 (PLA2) isoforms supporting their production within the cardiovascular system are not fully understood. To address this, we have studied platelets, endothelial cells, and leukocytes from 2 siblings with a homozygous loss-of-function mutation in group IVA cytosolic phospholipase A2 (cPLA2α). Chromatography/mass spectrometry was used to determine levels of a broad range of eicosanoids produced by isolated vascular cells, and in plasma and urine. Eicosanoid release data were paired with studies of cellular function. Absence of cPLA2α almost abolished eicosanoid synthesis in platelets (e.g., thromboxane A2, control 20.5 ± 1.4 ng/ml vs. patient 0.1 ng/ml) and leukocytes [e.g., prostaglandin E2 (PGE2), control 21.9 ± 7.4 ng/ml vs. patient 1.9 ng/ml], and this was associated with impaired platelet activation and enhanced inflammatory responses. cPLA2α-deficient endothelial cells showed reduced, but not absent, formation of prostaglandin I2 (prostacyclin; control 956 ± 422 pg/ml vs. patient 196 pg/ml) and were primed for inflammation. In the urine, prostaglandin metabolites were selectively influenced by cPLA2α deficiency. For example, prostacyclin metabolites were strongly reduced (18.4% of control) in patients lacking cPLA2α, whereas PGE2 metabolites (77.8% of control) were similar to healthy volunteer levels. These studies constitute a definitive account, demonstrating the fundamental role of cPLA2α to eicosanoid formation and cellular responses within the human circulation.—Kirkby, N. S., Reed, D. M., Edin, M. L., Rauzi, F., Mataragka, S., Vojnovic, I., Bishop-Bailey, D., Milne, G. L., Longhurst, H., Zeldin, D. C., Mitchell, J. A., Warner, T. D. Inherited human group IVA cytosolic phospholipase A2 deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation. PMID:26183771

  1. Re-187-Os-187, Pt-190-Os-186 Isotopic and Highly Siderophile Element Systematics of Group IVA Irons

    NASA Technical Reports Server (NTRS)

    Walker, R. J.; McCoy, T. J.; Schulte, R. F.; McDonough, W. F.; Ash, R. D.

    2005-01-01

    We have recently completed Re-187-Os-187 and Pt-190-Os-186 isotopic and elemental studies of the two largest magmatic iron meteorite groups, IIAB and IIIAB [1]. These studies revealed closed-system behavior of both isotopic systems, but complex trace element behavior for Re, Pt and Os in group IIIAB. Here we examine isotopic and trace elemental systematics of group IVA irons. The IVA irons are not as extensively fractionated as IIAB and IIIAB and their apparently less complex crystallization history may make for more robust interpretation of the relative partitioning behavior of Re, Pt and Os, as well as the other highly siderophile elements (HSE) measured here; Pd, Ru and Ir [e.g. 2]. An additional goal of our continuing research plan for iron meteorites is to assess the possibility of relating certain ungrouped irons with major groups via trace element modeling. Here, the isotopic and trace element systematics of the ungrouped irons Nedagolla and EET 83230 are compared with the IVA irons.

  2. ADVANCED SIMULATION CAPABILITY FOR ENVIRONMENTAL MANAGEMENT – CURRENT STATUS AND PHASE II DEMONSTRATION RESULTS

    SciTech Connect

    Seitz, Roger; Freshley, Mark D.; Dixon, Paul; Hubbard, Susan S.; Freedman, Vicky L.; Flach, Gregory P.; Faybishenko, Boris; Gorton, Ian; Finsterle, Stefan A.; Moulton, John D.; Steefel, Carl I.; Marble, Justin

    2013-06-27

    The U.S. Department of Energy (USDOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Toolsets and High-Performance Computing (HPC) Multiprocess Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, toolsets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial toolsets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  3. ADVANCED SIMULATION CAPABILITY FOR ENVIRONMENTAL MANAGEMENT- CURRENT STATUS AND PHASE II DEMONSTRATION RESULTS

    SciTech Connect

    Seitz, R.

    2013-02-26

    The U.S. Department of Energy (USDOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Toolsets and High-Performance Computing (HPC) Multiprocess Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, toolsets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial toolsets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  4. The North American Regional Climate Change Assessment Program: Overview of Phase I Results

    SciTech Connect

    Mearns, L. O.; Arritt, R.; Biner, S.; Bukovsky, Melissa; McGinnis, Seth; Sain, Steve; Caya, Daniel; Correia Jr., James; Flory, Dave; Gutowski, William; Takle, Gene; Jones, Richard; Leung, Lai-Yung R.; Moufouma-Okia, Wilfran; McDaniel, Larry; Nunes, A.; Qian, Yun; Roads, J.; Sloan, Lisa; Snyder, Mark A.

    2012-09-20

    The North American Regional Climate Change Assessment Program is an international effort designed to systematically investigate the uncertainties in regional scale projections of future climate and produce high resolution climate change scenarios using multiple regional climate models (RCMs) nested within atmosphere ocean general circulation models (AOGCMs) forced with the A2 SRES scenario, with a common domain covering the conterminous US, northern Mexico, and most of Canada. The program also includes an evaluation component (Phase I) wherein the participating RCMs are nested within 25 years of NCEP/DOE global reanalysis II. The grid spacing of the RCM simulations is 50 km.

  5. Phase I Field Test Results of an Innovative DNAPL Remediation Technology: The Hydrophobic Lance

    SciTech Connect

    Tuck, D.M.

    1999-01-28

    An innovative technology for recovery of pure phase DNAPL was deployed in the subsurface near the M-Area Settling Basin, continuing the support of the A/M Area Ground Water Corrective Action Program (per Part B requirements). This technology, the Hydrophobic Lance, operates by placing a neutral/hydrophobic surface (Teflon) in contact with the DNAPL. This changes the in situ conditions experienced by the DNAPL, allowing it to selectively drain into a sump from which it can be pumped. Collection of even small amounts of DNAPL can save years of pump-and-treat operation because of the generally low solubility of DNAPL components.

  6. NREL Unsteady Aerodynamics Experiment phase 3 test objectives and preliminary results

    SciTech Connect

    Simms, D.A.; Fingersh, L.J.; Butterfield, C.P.

    1995-09-01

    The United States Department of Energy and the National Renewable Energy Laboratory (NREL) are conducting research to improve a wind turbine technology. One program, the Combined Experiment, has focused on making measurements needed to understand aerodynamic and structural responses of horizontal-axis wind turbines (HAWT). A new phase of this program, the Unsteady Aerodynamics Experiment, will focus on quantifying unsteady aerodynamic phenomena prevalent install controlled HAWTs. Optimally twisted blades and innovative data acquisition systems will be used in these tests. data can now be acquired and viewed interactively during turbine operations. This paper describes the Unsteady Aerodynamics Experiment and highlights planned future research activities.

  7. Results.

    ERIC Educational Resources Information Center

    Zemsky, Robert; Shaman, Susan; Shapiro, Daniel B.

    2001-01-01

    Describes the Collegiate Results Instrument (CRI), which measures a range of collegiate outcomes for alumni 6 years after graduation. The CRI was designed to target alumni from institutions across market segments and assess their values, abilities, work skills, occupations, and pursuit of lifelong learning. (EV)

  8. Piotron. II. Methods and initial results of dynamic pion therapy in phase II studies

    SciTech Connect

    von Essen, C.F.; Blattmann, H.; Bodendoerfer, G.; Mizoe, J.; Pedroni, E.; Walder, E.; Zimmermann, A.

    1985-02-01

    Negative pi-meson (pion) therapy employing dynamic scanning with a focused spot of convergent beams has been in use since 1981 at SIN. Three-dimensional conformation of the treatment volume to the target volume can thus be achieved. Following previously reported Phase I and Ib clinical trials, a Phase II trial was initiated with the goal of treating primary deep-seated tumors in a dose optimization schedule which included stepwise increase of total pion dose and of target volume. Patients with multicentric superficial bladder tumors who were cystectomy candidates were initially selected. Since then, more invasive cases have been treated. Treatment reactions ranged from a faint erythema and increase of bladder frequency to dry desquamation, mild nausea, moderate dysuria, and moderate proctitis or diarrhea with mucus. These reactions were closely related to treatment volume and site. One severe late cystitis has occurred in a patient treated with 2 courses of pions (4475 rad). Mild to moderate late proctitis has been seen in 4 patients. Ten of 13 bladder cancer patients had local control of disease while all 3 pancreas or biliary tract cancer patients had microscopic residual disease locally at time of death from metastasis. A total of 11 of 17 patients are thus clinically or pathologically free of local tumor to time of last observation.

  9. Analysis, design, and experimental results for lightweight space heat receiver canisters, phase 1

    NASA Technical Reports Server (NTRS)

    Schneider, Michael G.; Brege, Mark A.; Heidenreich, Gary R.

    1991-01-01

    Critical technology experiments have been performed on thermal energy storage modules in support of the Brayton Advanced Heat Receiver program. The modules are wedge-shaped canisters designed to minimize the mechanical stresses that occur during the phase change of the lithium fluoride phase change material. Nickel foam inserts were used in some of the canisters to provide thermal conductivity enhancement and to distribute the void volume. Two canisters, one with a nickel foam insert, and one without, were thermally cycled in various orientations in a fluidized bed furnace. The only measurable impact of the nickel foam was seen when the back and short sides of the canister were insulated to simulate operation in the advanced receiver design. In tests with insulation, the furnace to back side delta T was larger in the canister with the nickel foam insert, probably due to the radiant absorptivity of the nickel. However, the differences in the temperature profiles of the two canisters were small, and in many cases the profiles matched fairly well. Computed Tomography (CT) was successfully used to nondestructively demarcate void locations in the canisters. Finally, canister dimensional stability, which was measured throughout the thermal cycling test program with an inspection fixture was satisfactory with a maximum change of 0.635 mm (0.025 in.).

  10. Jet-Surface Interaction Test: Phased Array Noise Source Localization Results

    NASA Technical Reports Server (NTRS)

    Podboy, Gary

    2012-01-01

    Subsonic jets are relatively simple. The peak noise source location gradually moves upstream toward the nozzle as frequency increases. 2) Supersonic jets are more complicated. The peak noise source location moves downstream as frequency increases through a BBSN hump. 3) In both subsonic and supersonic jets the peak noise source location corresponding to a given frequency of noise moves downstream as jet Mach number increases. 4) The noise generated at a given frequency in a BBSN hump is generated by a small number of shocks, not from all the shocks at the same time. 5) Single microphone spectrum levels decrease when the noise source locations measured with the phased array are blocked by a shielding surface. This consistency validates the phased array data and the stationary monopole source model used to process it. 6) Reflecting surface data illustrate that the law of reflection must be satisfied for noise to reflect off a surface toward an observer. 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) The low frequency noise created when a jet flow impinges on a surface comes primarily from the trailing edge regardless of the axial extent impacted by the flow.

  11. Influence of temperature on viral hemorrhagic septicemia (Genogroup IVa) in Pacific herring, Clupea pallasii Valenciennes

    USGS Publications Warehouse

    Hershberger, P.K.; Purcell, M.K.; Hart, L.M.; Gregg, J.L.; Thompson, R.L.; Garver, K.A.; Winton, J.R.

    2013-01-01

    An inverse relationship between water temperature and susceptibility of Pacific herring (Clupea pallasii) to viral hemorrhagic septicemia, genogroup IVa (VHS) was indicated by controlled exposure studies where cumulative mortalities, viral shedding rates, and viral persistence in survivors were greatest at the coolest exposure temperatures. Among groups of specific pathogen-free (SPF) Pacific herring maintained at 8, 11, and 15 °C, cumulative mortalities after waterborne exposure to viral hemorrhagic septicemia virus (VHSV) were 78%, 40%, and 13%, respectively. The prevalence of survivors with VHSV-positive tissues 25 d post-exposure was 64%, 16%, and 0% (at 8, 11 and 15 °C, respectively) with viral prevalence typically higher in brain tissues than in kidney/spleen tissue pools at each temperature. Similarly, geometric mean viral titers in brain tissues and kidney/spleen tissue pools decreased at higher temperatures, and kidney/spleen titers were generally 10-fold lower than those in brain tissues at each temperature. This inverse relationship between temperature and VHS severity was likely mediated by an enhanced immune response at the warmer temperatures, where a robust type I interferon response was indicated by rapid and significant upregulation of the herring Mx gene. The effect of relatively small temperature differences on the susceptibility of a natural host to VHS provides insights into conditions that preface periodic VHSV epizootics in wild populations throughout the NE Pacific.

  12. Crystal structure of soluble MD-1 and its interaction with lipid IVa

    SciTech Connect

    Yoon, Sung-il; Hong, Minsun; Han, Gye Won; Wilson, Ian A.

    2010-07-22

    Lipopolysaccharide (LPS) of Gram-negative bacteria is a common pathogen-associated molecular pattern (PAMP) that induces potent innate immune responses. The host immune response against LPS is triggered by myeloid differentiation factor 2 (MD-2) in association with Toll-like receptor 4 (TLR4) on the cell surface. The MD-2/TLR4-mediated LPS response is regulated by the evolutionarily related complex of MD-1 and Toll-like receptor homolog RP105. Here, we report crystallographic and biophysical data that demonstrate a previously unidentified direct interaction of MD-1 with LPS. The crystal structure of chicken MD-1 (cMD-1) at 2.0 {angstrom} resolution exhibits a {beta}-cup-like fold, similar to MD-2, that encloses a hydrophobic cavity between the two {beta}-sheets. A lipid-like moiety was observed inside the cavity, suggesting the possibility of a direct MD-1/LPS interaction. LPS was subsequently identified as an MD-1 ligand by native gel electrophoresis and gel filtration analyses. The crystal structure of cMD-1 with lipid IVa, an LPS precursor, at 2.4 {angstrom} resolution revealed that the lipid inserts into the deep hydrophobic cavity of the {beta}-cup-like structure, but with some important differences compared with MD-2. These findings suggest that soluble MD-1 alone, in addition to its complex with RP105, can regulate host LPS sensitivity.

  13. Thermal and impact histories of reheated group IVA, IVB, and ungrouped iron meteorites and their parent asteroids

    NASA Astrophysics Data System (ADS)

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

    2011-09-01

    Abstract- The microstructures of six reheated iron meteorites—two IVA irons, Maria Elena (1935), Fuzzy Creek; one IVB iron, Ternera; and three ungrouped irons, Hammond, Babb’s Mill (Blake’s Iron), and Babb’s Mill (Troost’s Iron)—were characterized using scanning and transmission electron microscopy, electron-probe microanalysis, and electron backscatter diffraction techniques to determine their thermal and shock history and that of their parent asteroids. Maria Elena and Hammond were heated below approximately 700-750 °C, so that kamacite was recrystallized and taenite was exsolved in kamacite and was spheroidized in plessite. Both meteorites retained a record of the original Widmanstätten pattern. The other four, which show no trace of their original microstructure, were heated above 600-700 °C and recrystallized to form 10-20 μm wide homogeneous taenite grains. On cooling, kamacite formed on taenite grain boundaries with their close-packed planes aligned. Formation of homogeneous 20 μm wide taenite grains with diverse orientations would have required as long as approximately 800 yr at 600 °C or approximately 1 h at 1300 °C. All six irons contain approximately 5-10 μm wide taenite grains with internal microprecipitates of kamacite and nanometer-scale M-shaped Ni profiles that reach approximately 40% Ni indicating cooling over 100-10,000 yr. Un-decomposed high-Ni martensite (α2) in taenite—the first occurrence in irons—appears to be a characteristic of strongly reheated irons. From our studies and published work, we identified four progressive stages of shock and reheating in IVA irons using these criteria: cloudy taenite, M-shaped Ni profiles in taenite, Neumann twin lamellae, martensite, shock-hatched kamacite, recrystallization, microprecipitates of taenite, and shock-melted troilite. Maria Elena and Fuzzy Creek represent stages 3 and 4, respectively. Although not all reheated irons contain evidence for shock, it was probably the main

  14. Advanced Simulation Capability for Environmental Management - Current Status and Phase II Demonstration Results - 13161

    SciTech Connect

    Seitz, Roger R.; Flach, Greg; Freshley, Mark D.; Freedman, Vicky; Gorton, Ian; Dixon, Paul; Moulton, J. David; Hubbard, Susan S.; Faybishenko, Boris; Steefel, Carl I.; Finsterle, Stefan; Marble, Justin

    2013-07-01

    The U.S. Department of Energy (US DOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Tool-sets and High-Performance Computing (HPC) Multi-process Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, tool-sets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial tool-sets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  15. NASA/General Electric broad-specification fuels combustion technology program - Phase I results and status

    NASA Technical Reports Server (NTRS)

    Dodds, W. J.; Ekstedt, E. E.; Bahr, D. W.; Fear, J. S.

    1982-01-01

    A program is being conducted to develop the technology required to utilize fuels with broadened properties in aircraft gas turbine engines. The first phase of this program consisted of the experimental evaluation of three different combustor concepts to determine their potential for meeting several specific emissions and performance goals, when operated on broadened property fuels. The three concepts were a single annular combustor; a double annular combustor; and a short single annular combustor with variable geometry. All of these concepts were sized for the General Electric CF6-80 engine. A total of 24 different configurations of these concepts were evaluated in a high pressure test facility, using four test fuels having hydrogen contents between 11.8 and 14%. Fuel effects on combustor performance, durability and emissions, and combustor design features to offset these effects were demonstrated.

  16. Orbit transfer vehicle engine study, phase A extension. Volume 2A: Study results

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Engine trade studies and systems analyses leading to a baseline engine selection for advanced expander cycle engine are discussed with emphasis on: (1) performance optimization of advanced expander cycle engines in the 10 to 20K pound thrust range; (2) selection of a recommended advanced expander engine configuration based on maximized performance and minimized mission risk, and definition of the components for this configuration; (3) characterization of the low thrust adaptation requirements and performance for the staged combustion engine; (4) generation of a suggested safety and reliability approach for OTV engines independent of engine cycle; (5) definition of program risk relationships between expander and staged combustion cycle engines; and (6) development of schedules and costs for the DDT&E, production, and operation phases of the 10K pound thrust expander engine program.

  17. Differential effects of viral hemorrhagic septicaemia virus (VHSV) genotypes IVa and IVb on gill epithelial and spleen macrophage cell lines from rainbow trout (Oncorhynchus mykiss).

    PubMed

    Pham, P H; Lumsden, J S; Tafalla, C; Dixon, B; Bols, N C

    2013-02-01

    The two most prominent genotypes of viral hemorrhagic septicemia virus (VHSV) are -I in the Northeastern Atlantic region and -IV in North America, but much more is known about the cellular pathogenesis of genotype -I than -IV. VHSV genotype -IV is divided into -IVa from the Northeast Pacific Ocean and -IVb from the Great Lakes and both of which are less virulent to rainbow trout than genotype -I. In this work, infections of VHSV-IVa and -IVb have been studied in two rainbow trout cell lines, RTgill-W1 from the gill epithelium, and RTS11 from spleen macrophages. RTgill-W1 produced infectious progeny of both VHSV-IVa and -IVb. However, VHSV-IVa was more infectious than -IVb toward RTgill-W1: -IVa caused cytopathic effect (CPE) at a lower viral titre, elicited CPE earlier, and yielded higher titres. By contrast, no CPE and no increase in viral titre were observed in RTS11 cultures infected with either genotype. Yet in RTS11 all six VHSV genes were expressed and antiviral genes, Mx2 and Mx3, were up regulated by VHSV-IVb and -IVa. However, replication appeared to terminate at the translational stage as viral N protein, presumably the most abundant of the VSHV proteins, was not detected in either infected RTS11 cultures. In RTgill-W1, Mx2 and Mx3 were up regulated to similar levels by both viral genotypes, while VHSV-IVa induced higher levels of IFN1, IFN2 and LGP2A than VHSV-IVb.

  18. DARPA counter-sniper program: Phase 1 Acoustic Systems Demonstration results

    NASA Astrophysics Data System (ADS)

    Carapezza, Edward M.; Law, David B.; Csanadi, Christina J.

    1997-02-01

    During October 1995 through May 1996, the Defense Advanced Research Projects Agency sponsored the development of prototype systems that exploit acoustic muzzle blast and ballistic shock wave signatures to accurately predict the location of gunfire events and associated shooter locations using either single or multiple volumetric arrays. The output of these acoustic systems is an estimate of the shooter location and a classification estimate of the caliber of the shooter's weapon. A portable display and control unit provides both graphical and alphanumeric shooter location related information integrated on a two- dimensional digital map of the defended area. The final Phase I Acoustic Systems Demonstration field tests were completed in May. These these tests were held at USMC Base Camp Pendleton Military Operations Urban Training (MOUT) facility. These tests were structured to provide challenging gunfire related scenarios with significant reverberation and multi-path conditions. Special shot geometries and false alarms were included in these tests to probe potential system vulnerabilities and to determine the performance and robustness of the systems. Five prototypes developed by U.S. companies and one Israeli developed prototype were tested. This analysis quantifies the spatial resolution estimation capability (azimuth, elevation and range) of these prototypes and describes their ability to accurately classify the type of bullet fired in a challenging urban- like setting.

  19. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study

    PubMed Central

    Bernard, Frederic; van Noesel, Max; Barkaoui, Mohamed; Bardet, Odile; Mura, Rosella; Arico, Maurizio; Piguet, Christophe; Gandemer, Virginie; Armari Alla, Corinne; Clausen, Niels; Jeziorski, Eric; Lambilliote, Anne; Weitzman, Sheila; Henter, Jan Inge; Van Den Bos, Cor

    2015-01-01

    An international phase 2 study combining cladribine and cytarabine (Ara-C) was initiated for patients with refractory, risk-organ–positive Langerhans cell histiocytosis (LCH) in 2005. The protocol, comprising at least two 5-day courses of Ara-C (1 g/m2 per day) plus cladribine (9 mg/m2 per day) followed by maintenance therapy, was administered to 27 patients (median age at diagnosis, 0.7 years; median follow-up, 5.3 years). At inclusion, all patients were refractory after at least 1 course of vinblastine (VBL) plus corticosteroid, all had liver and spleen involvement, and 25 patients had hematologic cytopenia. After 2 courses, disease status was nonactive (n = 2), better (n = 23), or stable (n = 2), with an overall response rate of 92%. Median disease activity scores decreased from 12 at the start of therapy to 3 after 2 courses (P < .0001). During maintenance therapy, 4 patients experienced reactivation in risk organs. There were 4 deaths; 2 were related to therapy toxicity and 2 were related to reactivation. All patients experienced severe toxicity, with World Health Organization grade 4 hematologic toxicity and 6 documented severe infections. The overall 5-year survival rate was 85% (95% confidence interval, 65.2%-94.2%). Thus, the combination of cladribine/Ara-C is effective therapy for refractory multisystem LCH but is associated with high toxicity. PMID:26194764

  20. Two-phase thermophilic anaerobic digestion process for biohythane production treating biowaste: preliminary results.

    PubMed

    Cavinato, C; Bolzonella, D; Fatone, F; Giuliano, A; Pavan, P

    2011-01-01

    This paper deals with the optimization of a two-phase anaerobic process treating biowaste for hydrogen and methane production. Neither physical nor chemical pre-treatments were used to optimize the process. The work was carried out at pilot scale, using two CSTRs (200 and 380 L working volume respectively) both maintained at thermophilic temperature (55 C) and fed semi-continuously with biowaste. The experiment was divided into three periods; during the first two periods the organic loading rate was maintained at 20 kg TVS/m3 d and the hydraulic retention time was changed from 6.6 to 3.3 days, while in the last period the digestate of the second reactor was recirculated to the first reactor in order to buffer the system and control pH at levels around 5. The HRT was maintained at 3.3 days and the OLR was decreased at 16.5 kg TVS/m3 d. The best yield was obtained in the last period where a specific hydrogen production of 50.9 L/kg VSfed was reached, with a H2 content in biogas from the first reactor of 36%. The methanogenic stage after the hydrogen conversion reached a specific biogas production of 0.62 m3/kg VSfed and an overall organic removal above 70%, without any stability problem. The overall biogas production was some 1.5 m3 per day with a gas composition of 10% H2 and 50% CH4.

  1. Arsenic pilot plant operation and results - Socorro Springs, New Mexico - phase 1.

    SciTech Connect

    Aragon, Malynda Jo; Everett, Randy L.; Siegel, Malcolm Dean; Kottenstette, Richard Joseph; Holub, William E. Jr; Wright, Jeremy B.; Dwyer, Brian P.

    2007-05-01

    Sandia National Laboratories (SNL) is conducting pilot scale evaluations of the performance and cost of innovative water treatment technologies aimed at meeting the recently revised arsenic maximum contaminant level (MCL) for drinking water. The standard of 10 {micro}g/L (10 ppb) is effective as of January 2006. The first pilot tests have been conducted in New Mexico where over 90 sites that exceed the new MCL have been identified by the New Mexico Environment Department. The pilot test described in this report was conducted in Socorro New Mexico between January 2005 and July 2005. The pilot demonstration is a project of the Arsenic Water Technology Partnership program, a partnership between the American Water Works Association Research Foundation (AwwaRF), SNL and WERC (A Consortium for Environmental Education and Technology Development). The Sandia National Laboratories pilot demonstration at the Socorro Springs site obtained arsenic removal performance data for five different adsorptive media under constant ambient flow conditions. Well water at Socorro Springs has approximately 42 ppb arsenic in the oxidized (arsenate-As(V)) redox state with moderate amounts of silica, low concentrations of iron and manganese and a slightly alkaline pH (8). The study provides estimates of the capacity (bed volumes until breakthrough at 10 ppb arsenic) of adsorptive media in the same chlorinated water. Near the end of the test the feedwater pH was lowered to assess the affect on bed capacity and as a prelude to a controlled pH study (Socorro Springs Phase 2).

  2. Phase 1 results from a study of romidepsin in combination with gemcitabine in patients with advanced solid tumors.

    PubMed

    Jones, Suzanne F; Infante, Jeffrey R; Spigel, David R; Peacock, Nancy W; Thompson, Dana S; Greco, F Anthony; McCulloch, William; Burris, Howard A

    2012-07-01

    Romidepsin is a potent histone deacetylase inhibitor; preclinical studies showed potential synergy with the nucleoside analog gemcitabine. This phase 1 trial was conducted to determine the maximum tolerated dose for two schedules of romidepsin plus gemcitabine in patients with advanced solid tumors in which gemcitabine had previously demonstrated clinical activity. The recommended phase 2 dose was 12 mg/m(2) romidepsin plus 800 mg/m(2) gemcitabine on days 1 and 15 every 28 days. Results suggest additive hematologic toxicities of romidepsin plus gemcitabine, but the level of antitumor activity observed warrants more formal trials of this combination to further assess safety and efficacy.

  3. Syracuse Univesity Test Report On Uptake Factor Resulting From A Dropped Storage Container - Phase II

    SciTech Connect

    Gao, Zhi; Zhang, Jianshun S.

    2012-01-01

    rate was once every 2 seconds during the first 2 hours. A test procedure was developed and verified. A total of thirty two drop tests were performed, eight in Phase I and twenty four in Phase II, covering variations in dropping height (8 ft or 4 ft from the floor), room air movement (0.25-0.30 m/s or 0.10-0.15 m/s near the ceiling), landing scenario (on a flat plate or a block), and lid condition (¼” lid hole or no lid). There were ten tests with flat plate and ¼” lid hole, ten tests with flat plate no lid and twelve tests with block no lid.

  4. Differentiation therapy in poor risk myeloid malignancies: Results of companion phase II studies.

    PubMed

    Norsworthy, Kelly J; Cho, Eunpi; Arora, Jyoti; Kowalski, Jeanne; Tsai, Hua-Ling; Warlick, Erica; Showel, Margaret; Pratz, Keith W; Sutherland, Lesley A; Gore, Steven D; Ferguson, Anna; Sakoian, Sarah; Greer, Jackie; Espinoza-Delgado, Igor; Jones, Richard J; Matsui, William H; Smith, B Douglas

    2016-10-01

    Pre-clinical data in non-M3 AML supports the use of differentiation therapy, but clinical activity has been limited. Myeloid growth factors can enhance anti-leukemic activity of differentiating agents in vitro. We conducted companion phase II trials investigating sargramostim (GM-CSF) 125μg/m(2)/day plus 1) bexarotene (BEX) 300mg/m(2)/day or 2) entinostat (ENT) 4-8mg/m(2)/week in patients with MDS or relapsed/refractory AML. Primary endpoints were response after at least two treatment cycles and toxicity. 26 patients enrolled on the BEX trial had a median of 2 prior treatments and 24 enrolled on the ENT trial had a median of 1. Of 13 response-evaluable patients treated with BEX, the best response noted was hematologic improvement in neutrophils (HI-N) seen in 4 (31%) patients; none achieved complete (CR) or partial remission (PR). Of 10 treated with ENT, there was 1 (10%) partial remission (PR) and 2 (20%) with HI-N. The secondary endpoint responses of HI-N with each combination were accompanied by a numerical increase in ANC (BEX: 524 to 931 cells/mm(3), p=0.096; ENT: 578 to 1 137 cells/mm(3), p=0.15) without increasing marrow blasts. Shared grade 3-4 non-hematologic toxicities included febrile neutropenia, bone pain, fatigue, and dyspnea. GM-CSF plus either BEX or ENT are well tolerated in resistant and refractory MDS and AML and showed modest clinical and biologic activity, most commonly HI-N.

  5. A novel, flat, electronically-steered phased array transducer for tissue ablation: preliminary results.

    PubMed

    Ellens, Nicholas P K; Lucht, Benjamin B C; Gunaseelan, Samuel T; Hudson, John M; Hynynen, Kullervo H

    2015-03-21

    Flat, λ/2-spaced phased arrays for therapeutic ultrasound were examined in silico and in vitro. All arrays were made by combining modules made of 64 square elements with 1.5 mm inter-element spacing along both major axes. The arrays were designed to accommodate integrated, co-aligned diagnostic transducers for targeting and monitoring. Six arrays of 1024 elements (16 modules) and four arrays of 6144 elements (96 modules) were modelled and compared according to metrics such as peak pressure amplitude, focal size, ability to be electronically-steered far off-axis and grating lobe amplitude. Two 1024 element prototypes were built and measured in vitro, producing over 100 W of acoustic power. In both cases, the simulation model of the pressure amplitude field was in good agreement with values measured by hydrophone. Using one of the arrays, it was shown that the peak pressure amplitude dropped by only 24% and 25% of the on-axis peak pressure amplitude when steered to the edge of the array (40 mm) at depths of 30 mm and 50 mm. For the 6144 element arrays studied in in silico only, similarly high steerability was found: even when steered 100 mm off-axis, the pressure amplitude decrease at the focus was less than 20%, while the maximum pressure grating lobe was only 20%. Thermal simulations indicate that the modules produce more than enough acoustic power to perform rapid ablations at physiologically relevant depths and steering angles. Arrays such as proposed and tested in this study have enormous potential: their high electronic steerability suggests that they will be able to perform ablations of large volumes without the need for any mechanical translation.

  6. Two-phase thermophilic anaerobic digestion process for biohythane production treating biowaste: preliminary results.

    PubMed

    Cavinato, C; Bolzonella, D; Fatone, F; Giuliano, A; Pavan, P

    2011-01-01

    This paper deals with the optimization of a two-phase anaerobic process treating biowaste for hydrogen and methane production. Neither physical nor chemical pre-treatments were used to optimize the process. The work was carried out at pilot scale, using two CSTRs (200 and 380 L working volume respectively) both maintained at thermophilic temperature (55 C) and fed semi-continuously with biowaste. The experiment was divided into three periods; during the first two periods the organic loading rate was maintained at 20 kg TVS/m3 d and the hydraulic retention time was changed from 6.6 to 3.3 days, while in the last period the digestate of the second reactor was recirculated to the first reactor in order to buffer the system and control pH at levels around 5. The HRT was maintained at 3.3 days and the OLR was decreased at 16.5 kg TVS/m3 d. The best yield was obtained in the last period where a specific hydrogen production of 50.9 L/kg VSfed was reached, with a H2 content in biogas from the first reactor of 36%. The methanogenic stage after the hydrogen conversion reached a specific biogas production of 0.62 m3/kg VSfed and an overall organic removal above 70%, without any stability problem. The overall biogas production was some 1.5 m3 per day with a gas composition of 10% H2 and 50% CH4. PMID:22097052

  7. Relationship between theta-phase gamma-amplitude coupling and attention-deficit/hyperactivity behavior in children.

    PubMed

    Kim, Jun Won; Lee, Jaewon; Kim, Hyun-Jin; Lee, Young Sik; Min, Kyung Joon

    2015-03-17

    The Continuous Performance Test (CPT) is a valuable tool for assessing behavior in attention-deficit/hyperactivity disorder (ADHD). Quantitative electroencephalography (QEEG) is a promising tool for the diagnosis of ADHD. Recently, theta-phase gamma-amplitude coupling (TGC) measurement has received attention because it is a feasible method of assessing brain function. We investigated the relationship between CPT performance and EEG measures such as TGC and theta and gamma activity. EEGs were recorded from 68 volunteers from a camp for hyperactive children using a 19-electrode system. Their TGC, theta and 40 Hz gamma activity were estimated and compared with results obtained on the Korean ADHD Rating Scale (KARS) and the Intermediate Visual and Auditory (IVA) CPT. The results demonstrated significant negative partial correlations between TGC and the IVA CPT, such as the Response Control Quotient (RCQ) and Attention Quotient (AQ). TGC successfully identified the level of dysfunctional interaction of the attention/arousal system at a multi-scale large network level. It is thought that as the TGC increases, the efficacy of the system is very low or dysfunctional. Compensatory hyper-arousal patterns of the dysfunctional attention/arousal system may account for this effect. TGC is a promising neurophysiological marker for ADHD behavior in children.

  8. Orbit transfer vehicle engine study, phase A, extension 1: Volume 2: Study results

    NASA Technical Reports Server (NTRS)

    Mellish, J. A.

    1981-01-01

    Because of the advantage of the Advanced Expander Cycle Engine brought out in initial studies, further design optimization and comparative analyses were undertaken. The major results and conclusion derived are summarized. The primary areas covered are (1) thrust chamber geometry optimization, (2) expander cycle optimization, (3) alternate low thrust capability, (4) safety and reliability, (5) development risk comparison, and (6) cost comparisons. All of the results obtained were used to baseline the initial design concept for the OTV Advanced Expander Cycle Engine Point Design Study.

  9. New calorimetric system and some results of water phase transition research in plant roots.

    PubMed

    Bakradze, N; Kiziria, E; Sokhadze, V; Gogichaishvili, Sh; Vardidze, E

    2007-01-01

    The principle of operation and main parameters of the recently created scanning differential reverse microcalorimeter of the new generation are presented. The microcalorimeter is destined for studying water crystallization and ice melting processes in heterogeneous systems, including plant and animal cells and tissues in the temperature range of 20 to -55 degrees C. In order to obtain maximum information from the experimental results respective algorithms and applied software package were developed. The results of studies of water crystallization and ice melting processes in different parts of common plantain (Plantago major L.) root, as a certain model system, can give us information on the peculiarities of the studied processes in complex, heterogeneous systems.

  10. Detection and genetic characterization of PVL-positive ST8-MRSA-IVa and exfoliative toxin D-positive European CA-MRSA-Like ST1931 (CC80) MRSA-IVa strains in Bangladesh.

    PubMed

    Paul, Shyamal Kumar; Ghosh, Souvik; Kawaguchiya, Mitsuyo; Urushibara, Noriko; Hossain, Mohammad Akram; Ahmed, Salma; Mahmud, Chand; Jilani, Md Shariful Alam; Haq, Jalaluddin Ashraful; Ahmed, Abdullah Akhtar; Kobayashi, Nobumichi

    2014-08-01

    Severe skin lesions caused by Staphylococcus aureus infection are associated with production from bacterial cells of Panton-Valentine leukocidin (PVL), a typical virulence factor of community-acquired methicillin-resistant S. aureus (CA-MRSA), as well as other toxins represented by exfoliative toxins. Through a retrospective study of 26 S. aureus strains isolated from skin lesions of diabetic patients admitted to a hospital in Bangladesh, 2 PVL-gene-positive MRSA-IVa strains and 8 PVL-negative, exfoliative toxin D (ETD) gene (etd)-positive MRSA-IVa strains were isolated. A PVL-positive MRSA-IVa strain had a type I arginine catabolic mobile element (ACME), belonged to ST8/agr-type I/spa-type t121 (a variant of t008), and harbored blaZ, tet(K), msrA, and aph(3')-IIIa, which are mostly typical characteristics found in USA300, a predominant CA-MRSA clone in the United States. Another PVL-positive MRSA strain, belonging to ST1929 (CC88)/agr-type III/spa-type t3341, was negative for ACME, but possessed blaZ and tet(K). The etd-positive MRSA-IVa strains possessed the epidermal cell differentiation inhibitor B (EDIN-B)-encoding gene (edinB) and belonged to ST1931 (CC80)/agr-type III/spa-type t11023 (a variant of t044), which was genetic trait similar to that of the European CA-MRSA ST80 clone. However, unlike the European ST80 strains, the etd-positive MRSA strains detected in the present study harbored seb, sek, and seq, while they were negative for tet(K), aph(3')-IIIa, and fusB, showing susceptibility to fusidic acid. These findings suggested that etd-positive ST1931 MRSA strains belong to the same lineage as the European ST80 MRSA clone, evolving from a common ancestral clone via acquisition of a different pathogenicity island. This is the first report of a USA300-like MRSA-IV strain, PVL-positive ST1929 (CC88) MRSA-IV, and European ST80 CA-MRSA-like etd-positive ST1931 (CC80) MRSA-IV strains isolated in Bangladesh.

  11. Robonaut 2 - IVA Experiments On-Board ISS and Development Towards EVA Capability

    NASA Technical Reports Server (NTRS)

    Diftler, Myron; Hulse, Aaron; Badger, Julia; Thackston, Allison; Rogers, Jonathan

    2014-01-01

    Robonaut 2 (R2) has completed its fixed base activities on-board the ISS and is scheduled to receive its climbing legs in early 2014. In its continuing line of firsts, the R2 torso finished up its on-orbit activities on its stanchion with the manipulation of space blanket materials and performed multiple tasks under teleoperation control by IVA astronauts. The successful completion of these two IVA experiments is a key step in Robonaut's progression towards an EVA capability. Integration with the legs and climbing inside the ISS will provide another important part of the experience that R2 will need prior to performing tasks on the outside of ISS. In support of these on-orbit activities, R2 has been traversing across handrails in simulated zero-g environments and working with EVA tools and equipment on the ground to determine manipulation strategies for an EVA Robonaut. R2 made significant advances in robotic manipulation of deformable materials in space while working with its softgoods task panel. This panel features quarter turn latches that secure a space blanket to the task panel structure. The space blanket covers two cloth cubes that are attached with Velcro to the structure. R2 was able to open and close the latches, pull back the blanket, and remove the cube underneath. R2 simulated cleaning up an EVA worksite as well, by replacing the cube and reattaching the blanket. In order to interact with the softgoods panel, R2 has both autonomously and with a human in the loop identified and localized these deformable objects. Using stereo color cameras, R2 identified characteristic elements on the softgoods panel then extracted the location and orientation of the object in its field of view using stereo disparity and kinematic transforms. R2 used both vision processing and supervisory control to successfully accomplish this important task. Teleoperation is a key capability for Robonaut's effectiveness as an EVA system. To build proficiency, crewmembers have

  12. Analytical Round Robin for Elastic-Plastic Analysis of Surface Cracked Plates: Phase I Results

    NASA Technical Reports Server (NTRS)

    Wells, D. N.; Allen, P. A.

    2012-01-01

    An analytical round robin for the elastic-plastic analysis of surface cracks in flat plates was conducted with 15 participants. Experimental results from a surface crack tension test in 2219-T8 aluminum plate provided the basis for the inter-laboratory study (ILS). The study proceeded in a blind fashion given that the analysis methodology was not specified to the participants, and key experimental results were withheld. This approach allowed the ILS to serve as a current measure of the state of the art for elastic-plastic fracture mechanics analysis. The analytical results and the associated methodologies were collected for comparison, and sources of variability were studied and isolated. The results of the study revealed that the J-integral analysis methodology using the domain integral method is robust, providing reliable J-integral values without being overly sensitive to modeling details. General modeling choices such as analysis code, model size (mesh density), crack tip meshing, or boundary conditions, were not found to be sources of significant variability. For analyses controlled only by far-field boundary conditions, the greatest source of variability in the J-integral assessment is introduced through the constitutive model. This variability can be substantially reduced by using crack mouth opening displacements to anchor the assessment. Conclusions provide recommendations for analysis standardization.

  13. REVIEW OF RESULTS FOR THE OECD/NEA PHASE VII BENCHMARK: STUDY OF SPENT FUEL COMPOSITIONS FOR LONG TERM DISPOSAL

    SciTech Connect

    Radulescu, Georgeta; Wagner, John C

    2011-01-01

    This paper summarizes the problem specification and compares participants results for the OECD/NEA/WPNCS Expert Group on Burn-up Credit Criticality Safety Phase VII Benchmark Study of Spent Fuel Compositions for Long-Term Disposal. The Phase VII benchmark was developed to study the ability of relevant computer codes and associated nuclear data to predict spent fuel isotopic compositions and corresponding keff values in a cask configuration over the time duration relevant to spent nuclear fuel (SNF) disposal. The benchmark was divided into two sets of calculations: (1) decay calculations out to 1,000,000 years for provided pressurized-water-reactor (PWR) UO2 discharged fuel compositions and (2) burnup credit criticality calculations for a representative cask model at selected time steps. Contributions from 15 organizations and companies in 10 countries were submitted to the Phase VII benchmark exercise. This paper provides a description of the Phase VII benchmark and detailed comparisons of the participants isotopic compositions and keff values that were calculated with a diversity of computer codes and nuclear data sets. Differences observed in the calculated time-dependent nuclide densities are attributed to different decay data or code-specific numerical approximations. The variability of the keff results is consistent with the evaluated uncertainty associated with cross-section data.

  14. The Municipal Solid-State Street Lighting Consortium Public Outdoor Lighting Inventory: Phase I: Survey Results

    SciTech Connect

    Kinzey, Bruce R.; Smalley, Edward; Haefer, R.

    2014-09-30

    This document presents the results of a voluntary web-based inventory survey of public street and area lighting across the U.S. undertaken during the latter half of 2013.This survey attempts to access information about the national inventory in a “bottoms-up” manner, going directly to owners and operators. Adding to previous “top down” estimates, it is intended to improve understanding of the role of public outdoor lighting in national energy use.

  15. Phase transitions in cooperative coinfections: Simulation results for networks and lattices

    NASA Astrophysics Data System (ADS)

    Grassberger, Peter; Chen, Li; Ghanbarnejad, Fakhteh; Cai, Weiran

    2016-04-01

    We study the spreading of two mutually cooperative diseases on different network topologies, and with two microscopic realizations, both of which are stochastic versions of a susceptible-infected-removed type model studied by us recently in mean field approximation. There it had been found that cooperativity can lead to first order transitions from spreading to extinction. However, due to the rapid mixing implied by the mean field assumption, first order transitions required nonzero initial densities of sick individuals. For the stochastic model studied here the results depend strongly on the underlying network. First order transitions are found when there are few short but many long loops: (i) No first order transitions exist on trees and on 2-d lattices with local contacts. (ii) They do exist on Erdős-Rényi (ER) networks, on d -dimensional lattices with d ≥4 , and on 2-d lattices with sufficiently long-ranged contacts. (iii) On 3-d lattices with local contacts the results depend on the microscopic details of the implementation. (iv) While single infected seeds can always lead to infinite epidemics on regular lattices, on ER networks one sometimes needs finite initial densities of infected nodes. (v) In all cases the first order transitions are actually "hybrid"; i.e., they display also power law scaling usually associated with second order transitions. On regular lattices, our model can also be interpreted as the growth of an interface due to cooperative attachment of two species of particles. Critically pinned interfaces in this model seem to be in different universality classes than standard critically pinned interfaces in models with forbidden overhangs. Finally, the detailed results mentioned above hold only when both diseases propagate along the same network of links. If they use different links, results can be rather different in detail, but are similar overall.

  16. Virulence of viral hemorrhagic septicemia virus (VHSV) genotypes Ia, IVa, IVb, and IVc in five fish species.

    PubMed

    Emmenegger, Eveline J; Moon, Chang Hoon; Hershberger, Paul K; Kurath, Gael

    2013-12-12

    The susceptibility of yellow perch Perca flavescens, rainbow trout Oncorhynchus mykiss, Chinook salmon O. tshawytscha, koi Cyprinus carpio koi, and Pacific herring Clupea pallasii to 4 strains of viral hemorrhagic septicemia virus (VHSV) was assessed. Fish were challenged via intraperitoneal injection with high (1 × 106 plaque-forming units, PFU) and low (1 × 103 PFU) doses of a European strain (genotype Ia), and North American strains from the West coast (genotype IVa), Great Lakes (genotype IVb), and the East coast (genotype IVc). Pacific herring were exposed to the same VHSV strains, but at a single dose of 5 × 103 PFU ml-1 by immersion in static seawater. Overall, yellow perch were the most susceptible, with cumulative percent mortality (CPM) ranging from 84 to 100%, and 30 to 93% in fish injected with high or low doses of virus, respectively. Rainbow trout and Chinook salmon experienced higher mortalities (47 to 98% CPM) after exposure to strain Ia than to the other virus genotypes. Pacific herring were most susceptible to strain IVa with an average CPM of 80% and moderately susceptible (42 to 52% CPM) to the other genotypes. Koi had very low susceptibility (≤5.0% CPM) to all 4 VHSV strains. Fish tested at 7 d post challenge were positive for all virus strains, with yellow perch having the highest prevalence and concentrations of virus, and koi the lowest. While genotype Ia had higher virulence in salmonid species, there was little difference in virulence or host-specificity between isolates from subtypes IVa, IVb, and IVc.

  17. Virulence of viral hemorrhagic septicemia virus (VHSV) genotypes Ia, IVa, IVb, and IVc in five fish species.

    USGS Publications Warehouse

    Emmenegger, Eveline J.; Moon, Chang Hoon; Hershberger, Paul K.; Kurath, Gael

    2013-01-01

    The susceptibility of yellow perch Perca flavescens, rainbow trout Oncorhynchus mykiss, Chinook salmon O. tshawytscha, koi Cyprinus carpio koi, and Pacific herring Clupea pallasii to 4 strains of viral hemorrhagic septicemia virus (VHSV) was assessed. Fish were challenged via intraperitoneal injection with high (1 × 106 plaque-forming units, PFU) and low (1 × 103 PFU) doses of a European strain (genotype Ia), and North American strains from the West coast (genotype IVa), Great Lakes (genotype IVb), and the East coast (genotype IVc). Pacific herring were exposed to the same VHSV strains, but at a single dose of 5 × 103 PFU ml-1 by immersion in static seawater. Overall, yellow perch were the most susceptible, with cumulative percent mortality (CPM) ranging from 84 to 100%, and 30 to 93% in fish injected with high or low doses of virus, respectively. Rainbow trout and Chinook salmon experienced higher mortalities (47 to 98% CPM) after exposure to strain Ia than to the other virus genotypes. Pacific herring were most susceptible to strain IVa with an average CPM of 80% and moderately susceptible (42 to 52% CPM) to the other genotypes. Koi had very low susceptibility (≤5.0% CPM) to all 4 VHSV strains. Fish tested at 7 d post challenge were positive for all virus strains, with yellow perch having the highest prevalence and concentrations of virus, and koi the lowest. While genotype Ia had higher virulence in salmonid species, there was little difference in virulence or host-specificity between isolates from subtypes IVa, IVb, and IVc.  

  18. Purification, crystallization and preliminary X-ray analysis of Enterococcus casseliflavus aminoglycoside-2′′-phosphotransferase-IVa

    PubMed Central

    Toth, Marta; Vakulenko, Sergei; Smith, Clyde A.

    2010-01-01

    The deactivation of aminoglycoside antibiotics by chemical modification is one of the major sources of bacterial resistance to this family of therapeutic compounds, which includes the clinically relevant drugs streptomycin, kanamycin and gentamicin. The aminoglycoside phosphotransferases (APHs) form one such family of enzymes responsible for this resistance. The gene encoding one of these enzymes, aminoglycoside-2′′-phosphotransferase-IVa [APH(2′′)-IVa] from Enterococcus casseliflavus, has been cloned and the protein (comprising 306 amino-acid residues) has been expressed in Escherichia coli and purified. The enzyme was crystallized in three substrate-free forms. Two of the crystal forms belonged to the orthorhombic space group P212121 with similar unit-cell parameters, although one of the crystal forms had a unit-cell volume that was approximately 13% smaller than the other and a very low solvent content of around 38%. The third crystal form belonged to the monoclinic space group P21 and preliminary X-ray diffraction analysis was consistent with the presence of two molecules in the asymmetric unit. The orthorhombic crystal forms of apo APH(2′′)-IVa both diffracted to 2.2 Å resolution and the monoclinic crystal form diffracted to 2.4 Å resolution; synchrotron diffraction data were collected from these crystals at SSRL (Stanford, California, USA). Structure determination by molecular replacement using the structure of the related enzyme APH(2′′)-IIa is proceeding. PMID:20057078

  19. Neoadjuvant radiochemotherapy for locally advanced gastric cancer: Long-term results of a phase I trial

    SciTech Connect

    Allal, Abdelkarim S. . E-mail: abdelkarim.allal@hcuge.ch; Zwahlen, Daniel; Bruendler, Marie-Anne; Peyer, Raymond de; Morel, Philippe; Huber, Olivier; Roth, Arnaud D.

    2005-12-01

    Purpose: To assess the long-term results of radiation therapy (RT) when added preoperatively to systemic chemotherapy in patients with locally advanced gastric cancer. Methods and Materials: Patients presenting with T3-4 or N+ gastric cancer received two cycles of cisplatin 100 mg/m{sup 2} d1, 5FU 800 mg/m{sup 2} d1-4, and Leucovorin 60 mg twice daily d1-4; one cycle before and one concomitantly with hyperfractionated RT (median dose, 38.4; range, 31.2-45.6 Gy). All patients underwent a total or subtotal gastrectomy with D2 lymph node resection. Results: Nineteen patients were accrued and 18 completed the neoadjuvant therapeutic program. All patients were subsequently operated and no fatality occurred. At a mean follow-up of 8 years for the surviving patients, no severe late toxicity was observed. The 5-year locoregional control, disease-free, and overall survival were of 85%, 41%, and 35%, respectively. The peritoneum was the most frequent site of relapse. Among long terms survivors, no severe (Radiation Therapy Oncology Group Grade 3-4) late complication was reported. Conclusions: The present neoadjuvant treatment does not seem to increase the operative risk, nor the late side effects. The encouraging locoregional control rate suggests that the neoadjuvant approach should be considered for future trials in locally advanced gastric cancer. Also, the frequency of peritoneal recurrence stresses the need for a more efficient systemic or intraperitoneal treatment.

  20. The Eurosdr Project "RADIOMETRIC Aspects of Digital Photogrammetric IMAGES" - Results of the Empirical Phase

    NASA Astrophysics Data System (ADS)

    Honkavaara, E.; Arbiol, R.; Markelin, L.; Martínez, L.; Bovet, S.; Bredif, M.; Chandelier, L.; Heikkinen, V.; Korpela, I.; Lelegard, L.; Pérez, F.; Schläpfer, D.; Tokola, T.

    2011-09-01

    This article presents the empirical research carried out in the context of the multi-site EuroSDR project "Radiometric aspects of digital photogrammetric images" and provides highlights of the results. The investigations have considered the vicarious radiometric and spatial resolution validation and calibration of the sensor system, radiometric processing of the image blocks either by performing relative radiometric block equalization or into absolutely reflectance calibrated products, and finally aspects of practical applications on NDVI layer generation and tree species classification. The data sets were provided by Leica Geosystems ADS40 and Intergraph DMC and the participants represented stakeholders in National Mapping Authorities, software development and research. The investigations proved the stability and quality of evaluated imaging systems with respect to radiometry and optical system. The first new-generation methods for reflectance calibration and equalization of photogrammetric image block data provided promising accuracy and were also functional from the productivity and usability points of view. The reflectance calibration methods provided up to 5% accuracy without any ground reference. Application oriented results indicated that automatic interpretation methods will benefit from the optimal use of radiometrically accurate multi-view photogrammetric imagery.

  1. [Citalopram in depression (results of an open multicenter study in phase IV of the clinical trial)].

    PubMed

    Vinar, O; Svestka, J; Koníková, M

    1993-12-01

    249 depressed patients were treated by 35 psychiatrists in an open multicenter trial during 6 weeks with citalopram. The protocol enabled that naturalistic treatment conditions could be kept. The results were rated with the help of the Clinical Global Impression (CGI) scale. The treatment was successful in 77% of the patients. 5 patients dropped out because of adverse effects, 8 patients did not finish the trial due to insufficient efficacy. In 160 patients (64.2%) no adverse effects were registered. Transient mild headaches in 8.4% and nausea in 4% were the most frequent adverse events. The best effects were observed in patients who were rated as moderately ill (82.8% ameliorated) at pretreatment. Nevertheless, also 66.7% of those rated as severely ill before the treatment improved substantially. In patients treated with higher doses than 20 mg/day, the improvement rate was not higher than in those treated with 20 mg daily. PMID:8124734

  2. Phase 1 development of an aquifer heat storage facility. Part 1: Summary and results

    NASA Astrophysics Data System (ADS)

    Harasim, A.; Weissenbach, B.

    1982-03-01

    A surface aquifer pilot plan was defined. Several versions of construction were drafted and the costs were calculated for variable site conditions. Aquifer heat storage facilities larger than 5,000 cu m (water equivalent) are cheaper than any known storage concept. Simultaneous with technical and economic studies, problems of chemical mass transport in two typical soil materials (calcareous gravel water and red marl water) were investigated in lab tests. Special attention was paid to the biological behavior of a wet gravel bed in view of the possibility of clogging by slime. Recommendations are given to ensure safe operation of the storage plant. Corrosion in the storage facility was considered for various materials. Results show that cement structures are preferred.

  3. The VLTI focal instrument Amber: results of the first phase of the alignment, integration, and verification in Paranal

    NASA Astrophysics Data System (ADS)

    Robbe-Dubois, Sylvie; Petrov, Romain G.; Lagarde, Stephane; Antonelli, Pierre; Bresson, Yves; Roussel, Alain; Mourard, Denis; Malbet, Fabien; Millour, Florentin; Zins, Gerard; Delboulbe, Alain; Duvert, Gilles; Gluck, Laurence; Kern, Pierre Y.; Le Coarer, Etienne P.; Rousselet-Perraut, Karine; Tatulli, Eric; Beckmann, Udo; Heininger, Matthias; Weigelt, Gerd P.; Lisi, Franco; Stefanini, Paolo; Accardo, Matteo; Gil, Carla S.; Vannier, Martin; Haddad, Nicholas; Housen, Nico; Kiekebusch, Mario; Mardones, Pedro; Puech, Florence; Rantakyro, Fredrik T.; Richichi, Andrea; Schoeller, Markus

    2004-10-01

    AMBER, Astronomical Multi BEam combineR, is the near-infrared focal instrument dedicated to the VLTI. It is designed to combine three of the VLTI Telescopes and to work simultaneously in the J, H and K spectral bands (1.0 to 2.4 μm). The project successfully passed the Preliminary Acceptance in Europe in November 2003, resulting in the validation of the instrument laboratory performance1, of the compliance with the initial scientific specifications, and of the acceptance of ESO for AMBER to be part of the VLTI. After the transportation of the instrument to Paranal, Chile in January 2004, the Assembly Integration and Verification phase occurred mid-March to succeed with the first fringes observing bright stars with the VLTI siderostats. This paper describes the different steps of the AIV and the first results in terms of instrumental stability, estimated visibility and differential phase.

  4. Results of Phase 2 postburn drilling, coring, and logging: Rocky Mountain 1 Underground Coal Gasification Test, Hanna, Wyoming

    SciTech Connect

    Oliver, R.L.; Lindblom, S.R.; Covell, J.R.

    1991-02-01

    The Rocky Mountain 1 (RM1) Underground Coal Gasification (UCG) site consisted of two different module configurations: the controlled retracting injection point (CRIP) and elongated linked well (ELW) configurations. The postburn coring of the RM1 UCG site was designed in two phases to fulfill seven objectives outlined in Western Research Institute`s Annual Project Plan for 1989 (Western Research Institute 1989). The seven objectives were to (1) delineate the areal extent of the cavities, (2) identify the extent of roof collapse, (3) obtain samples of all major cavity rock types, (4) characterize outflow channels and cavity stratigraphy, (5) characterize the area near CRIP points and ignition points, (6) further define the structural geology of the site, and (7) identify the vertical positioning of the horizontal process wells within the coal seam. Phase 1 of the coring was completed during the summer of 1989 and served to partially accomplish all seven objectives. A detailed description of Phase 1 results was presented in a separate report (Lindblom et al. 1990). Phase 2, completed during the summer of 1990, was designed to complete the seven objectives; more specifically, to further define the areal extent and location of the cavities, to evaluate the outflow channels for both modules, and to further characterize the structural geology in the ELW module area.

  5. Results of Phase 2 postburn drilling, coring, and logging: Rocky Mountain 1 Underground Coal Gasification Test, Hanna, Wyoming

    SciTech Connect

    Oliver, R.L.; Lindblom, S.R.; Covell, J.R.

    1991-02-01

    The Rocky Mountain 1 (RM1) Underground Coal Gasification (UCG) site consisted of two different module configurations: the controlled retracting injection point (CRIP) and elongated linked well (ELW) configurations. The postburn coring of the RM1 UCG site was designed in two phases to fulfill seven objectives outlined in Western Research Institute's Annual Project Plan for 1989 (Western Research Institute 1989). The seven objectives were to (1) delineate the areal extent of the cavities, (2) identify the extent of roof collapse, (3) obtain samples of all major cavity rock types, (4) characterize outflow channels and cavity stratigraphy, (5) characterize the area near CRIP points and ignition points, (6) further define the structural geology of the site, and (7) identify the vertical positioning of the horizontal process wells within the coal seam. Phase 1 of the coring was completed during the summer of 1989 and served to partially accomplish all seven objectives. A detailed description of Phase 1 results was presented in a separate report (Lindblom et al. 1990). Phase 2, completed during the summer of 1990, was designed to complete the seven objectives; more specifically, to further define the areal extent and location of the cavities, to evaluate the outflow channels for both modules, and to further characterize the structural geology in the ELW module area.

  6. Phase 3 integrated water recovery testing at MSFC: Single loop test results and lessons learned

    NASA Technical Reports Server (NTRS)

    Carter, Donald Layne; Bagdigian, Robert M.

    1993-01-01

    A series of tests has been conducted at the NASA Marshall Space Flight Center (MSFC) to evaluate the performance of the Space Station Freedom (SSF) water recovery system. Potable and urine reclamation processors were integrated with waste water generation equipment and sucessfully operated for a total of 144 days. This testing marked the first occasion in which the waste feed sources for the previous potable and hygiene loops were combined into a single loop and processed to potable water quality. Reclaimed potable water from the combined waste waters routinely met the SSF water quality specifications.In the last stage of testing, data was obtained that indicated that the water processor (WP) presterilizer may not be required to meet the potable water quality specification. The removal of the presterilizer from the Water Processor design would provide a significant power savings, though an increase in the residence time of the catalytic oxidation reactor may be required to meet the potable microbial and total Organic Carbon specifications. This paper summarizes the test objectives, system design, test activities/protocols, significant results/anomalies and major lessons learned.

  7. Safety of gadoxetate disodium: results from six clinical phase IV studies in 8194 patients

    PubMed Central

    Kim, So Yeon; Sakaguchi, Toshiaki; Dohanish, Susan; Breuer, Josy

    2015-01-01

    Background Safety data on routine clinical use of gadoxetate disodium for liver magnetic resonance imaging (MRI) is not reported yet. Purpose To assess the safety profile of gadoxetate disodium for liver MRI in the routine clinical setting. Material and Methods Six multicenter studies were performed in Europe, USA, Australia, and Asia to evaluate the safety and efficacy of gadoxetate disodium (Primovist®/Eovist®) enhanced liver MRI. Patients received a single intravenous bolus injection of the standard approved dose of 0.025 mmol/kg body weight (0.1 mL/kg). The number of patients, the characteristics of adverse events, related adverse events, and serious adverse events were analyzed. Results A total of 8194 patients were included in the database. A total of 141 patients (1.7%) reported 230 AEs of which 129 were considered being related to the use of gadoxetate disodium by the investigators. None of the AEs in the pediatric population (n = 52) were related. The most frequent AEs independent of relationship to the drug included dyspnea (25/0.31%), nausea (22/0.27%), liver disorders (13/0.16%), and renal disorders (9/0.11%). Nine related SAEs were recorded. No patient died during the studies. Conclusion Gadoxetate disodium for liver MRI is safe and well tolerated in the routine clinical setting. PMID:26048848

  8. Measurement and model results for gas phase OH and H2SO4 during PROPHET 2001.

    NASA Astrophysics Data System (ADS)

    Tanner, D.; Sjostedt, S.; Huey, G.; Slusher, D.; Chen, G.; Lefer, B.; Shetter, R.; Carroll, M.; Hengel, S.; Fortner, E.; Young, V.

    2002-12-01

    During the summer of 2001 a Chemical Ionization Mass Spectrometer (CIMS) was installed on top of the PROPHET tower to measure OH and H2SO4. Both OH and H2SO4 have a strong diurnal variation and correlate well with the measured ozone photolysis rate. Typical OH nighttime values are below the detection limit of 3e5 molecules cm-3. The maximum daytime value varied from 1-5 e6 molecules cm-3 with the highest OH levels corresponding to the lowest isoprene mixing ratios. The nighttime results are inconsistent with previous LIF measurements of high nighttime OH levels at this site and may indicate a systematic difference between the two techniques. However, the midday measured OH data is approximately 50% higher than the preliminary midday model values and is in accord with the previous LIF observations. A more detailed comparison of constrained photochemical models predictions to the observed OH levels will be presented. The daytime H2SO4 concentrations were highly variable and exceeded 5e7 molecules cm-3 on two days under "clean" northerly flow conditions. Evidence will be presented that suggest the source of the relatively high sulfuric acid concentrations is a large nickel smelting operation in Sudbury, Ontario. The nighttime levels of sulfuric acid were typically below the detection limit of the instrument of approximately 1e5 molecules cm-3. This data is consistent with the measured OH and suggests that large nighttime sources of radicals are not present in this environment.

  9. Development of marketable solar assisted heat pumps. Phase II. Summary report, technical results

    SciTech Connect

    Hundt, R.; Heard, S.

    1981-02-20

    A water source heat pump has been designed that is capable of operating over the range from 40 to 110/sup 0/F entering water temperature and has a heating coefficient of performance greater than six in the upper portion of this range. A computerized heat pump balance program was written to allow the performance of either a water-to-water or a water-to-air heat pump to be predicted in either the heating or cooling mode. A detailed program description, flow charts, and sample outputs are appended. The balance program was used to specify components for a high efficiency water-to-water and a high efficiency water-to-air heat pump. Performance predictions for both units in heating and in cooling are included. The water-to-water and water-to-air performance predictions were compared. The water-to-air approach was clearly superior. A detailed design and layout was done for the three solar-assisted water-to-air heat pump. A horizontal configuration was chosen for marketability reasons. The design was made consistent with high quantity production equipment available in our factories and should result in the lowest possible manufacturing cost. A key question to be answered in this project is whether a reciprocating compressor can operate without damage at the high suction pressures characteristic to the inline SAHP. Reciprocating compressors are normally applied in applications with maximum suction pressures equal to a 55/sup 0/F saturated suction temperature. An accelerated life test was performed on low speed at 85/sup 0/F saturated suction temperature and 100/sup 0/F saturated condensing temperature. After 465 hours at these severe conditions no performance degradation or physical damage was noted. Tests on high speed at 70/sup 0/F saturated suction temperature are in progress and should define the limits where the compressor may be safely operated.

  10. Hypofractionated Versus Conventionally Fractionated Radiotherapy for Prostate Carcinoma: Final Results of Phase III Randomized Trial

    SciTech Connect

    Yeoh, Eric E.; Botten, Rochelle J.; Butters, Julie; Di Matteo, Addolorata C.; Holloway, Richard H.; Fowler, Jack

    2011-12-01

    Purpose: To evaluate the long-term efficacy and toxicity of a hypofractionated (55 Gy in 20 fractions within 4 weeks) vs. a conventionally fractionated (64 Gy in 32 fractions within 6.5 weeks) dose schedule for radiotherapy (RT) for localized carcinoma of the prostate. Methods and Materials: A total of 217 patients were randomized to either the hypofractionated (n = 108) or the conventional (n = 109) dose schedule. Most patients (n = 156) underwent RT planning and RT using a two-dimensional computed tomography method. Efficacy using the clinical, radiologic, and prostate-specific antigen data in each patient was evaluated before RT and at predetermined intervals after RT until death. Gastrointestinal and genitourinary toxicity using the modified Late Effect in Normal Tissue - Subjective Objective Management Analytic (LENT-SOMA) scales was also evaluated before and at intervals after RT to 60 months. Results: The whole group has now been followed for a median of 90 months (range, 3-138). Of the 217 patients, 85 developed biochemical relapse (nadir prostate-specific antigen level + 2 {mu}g/L), 36 in the hypofractionated and 49 in the conventional group. The biochemical relapse-free, but not overall, survival at 90 months was significantly better with the hypofractionated (53%) than with the conventional (34%) schedule. Gastrointestinal and genitourinary toxicity persisted 60 months after RT and did not differ between the two dose schedules. Multivariate analyses revealed that the conventional schedule was of independent prognostic significance, not only for biochemical failure, but also for an increased risk of worse genitourinary symptoms at 4 years. Conclusions: A therapeutic advantage of the hypofractionated compared with the conventional dose schedule for RT of prostate cancer was evident at 90 months in the present study.

  11. Review of the WECC EDT phase 2 EIM benefits analysis and results report.

    SciTech Connect

    Veselka, T.D.; Poch, L.A.; Botterud, A.

    2012-04-05

    A region-wide Energy Imbalance Market (EIM) was recently proposed by the Western Electricity Coordinating Council (WECC). In order for the Western Area Power Administration (Western) to make more informed decisions regarding its involvement in the EIM, Western asked Argonne National Laboratory (Argonne) to review the EIM benefits study (the October 2011 revision) performed by Energy and Environmental Economics, Inc. (E3). Key components of the E3 analysis made use of results from a study conducted by the National Renewable Energy Laboratory (NREL); therefore, we also reviewed the NREL work. This report examines E3 and NREL methods and models used in the EIM study. Estimating EIM benefits is very challenging because of the complex nature of the Western Interconnection (WI), the variability and uncertainty of renewable energy resources, and the complex decisions and potentially strategic bidding of market participants. Furthermore, methodologies used for some of the more challenging aspects of the EIM have not yet matured. This review is complimentary of several components of the EIM study. Analysts and modelers clearly took great care when conducting detailed simulations of the WI using well-established industry tools under stringent time and budget constraints. However, it is our opinion that the following aspects of the study and the interpretation of model results could be improved upon in future analyses. The hurdle rate methodology used to estimate current market inefficiencies does not directly model the underlying causes of sub-optimal dispatch and power flows. It assumes that differences between historical flows and modeled flows can be attributed solely to market inefficiencies. However, flow differences between model results and historical data can be attributed to numerous simplifying assumptions used in the model and in the input data. We suggest that alternative approaches be explored in order to better estimate the benefits of introducing market

  12. Superior Dielectric Performance of Engineering Thermoplastic as a Result of In situ Embedding of Nanoscale Mixed-Phase Molybdenum Oxide

    NASA Astrophysics Data System (ADS)

    Qureshi, Nilam; Shinde, Manish; Ratheesh, R.; Bhalerao, Anand; Kale, Bharat; Mulik, Uttam; Amalnerkar, Dinesh P.

    2015-07-01

    To facilitate in situ generation of single and mixed-phase molybdenum oxide on the nanoscale in a network of polyphenylene sulfide (PPS), a novel polymer-inorganic solid-state reaction is proposed. Ammonium molybdate was homogeneously mixed with PPS in 1:1 molar ratio and heated at 285°C for different times (6 h, 24 h, or 48 h) under ambient conditions. The products were characterized by x-ray diffractometry, field emission scanning electron microscopy, and transmission electron microscopy. Structural investigations revealed the co-existence of mix-phased molybdenum oxide, i.e. dominant orthorhombic α-MoO3, and minor monoclinic Mo8O23 phases, within the modified PPS matrix. The resulting molybdenum oxide nanostructures had rod and sheet-like morphology in the PPS matrix. Dielectric measurements on pellets prepared from the resulting nanocomposites revealed improvement of the dielectric properties compared with values reported for pure PPS. The resulting nano-composites may exhibit properties synergistically derived from those of their components (molybdenum oxide and PPS), i.e. lower dielectric constant and loss tangent, enabling application as relatively high-temperature capacitors.

  13. RELAP5-3D results for phase I (Exercise 2) of the OECD/NEA MHTGR-350 MW benchmark

    SciTech Connect

    Strydom, G.; Epiney, A. S.

    2012-07-01

    The coupling of the PHISICS code suite to the thermal hydraulics system code RELAP5-3D has recently been initiated at the Idaho National Laboratory (INL) to provide a fully coupled prismatic Very High Temperature Reactor (VHTR) system modeling capability as part of the NGNP methods development program. The PHISICS code consists of three modules: INSTANT (performing 3D nodal transport core calculations), MRTAU (depletion and decay heat generation) and a perturbation/mixer module. As part of the verification and validation activities, steady state results have been obtained for Exercise 2 of Phase I of the newly-defined OECD/NEA MHTGR-350 MW Benchmark. This exercise requires participants to calculate a steady-state solution for an End of Equilibrium Cycle 350 MW Modular High Temperature Reactor (MHTGR), using the provided geometry, material, and coolant bypass flow description. The paper provides an overview of the MHTGR Benchmark and presents typical steady state results (e.g. solid and gas temperatures, thermal conductivities) for Phase I Exercise 2. Preliminary results are also provided for the early test phase of Exercise 3 using a two-group cross-section library and the Relap5-3D model developed for Exercise 2. (authors)

  14. RELAP5-3D Results for Phase I (Exercise 2) of the OECD/NEA MHTGR-350 MW Benchmark

    SciTech Connect

    Gerhard Strydom

    2012-06-01

    The coupling of the PHISICS code suite to the thermal hydraulics system code RELAP5-3D has recently been initiated at the Idaho National Laboratory (INL) to provide a fully coupled prismatic Very High Temperature Reactor (VHTR) system modeling capability as part of the NGNP methods development program. The PHISICS code consists of three modules: INSTANT (performing 3D nodal transport core calculations), MRTAU (depletion and decay heat generation) and a perturbation/mixer module. As part of the verification and validation activities, steady state results have been obtained for Exercise 2 of Phase I of the newly-defined OECD/NEA MHTGR-350 MW Benchmark. This exercise requires participants to calculate a steady-state solution for an End of Equilibrium Cycle 350 MW Modular High Temperature Reactor (MHTGR), using the provided geometry, material, and coolant bypass flow description. The paper provides an overview of the MHTGR Benchmark and presents typical steady state results (e.g. solid and gas temperatures, thermal conductivities) for Phase I Exercise 2. Preliminary results are also provided for the early test phase of Exercise 3 using a two-group cross-section library and the Relap5-3D model developed for Exercise 2.

  15. Application of Phase Smoothing Pseudo Range PPP/INS Tightly Coupled Technique in Improving the Results of Low Precision MEMS

    NASA Astrophysics Data System (ADS)

    Luo, X.

    2015-12-01

    In land surveying and engineering surveying, we need to obtain high precision navigation results. However, due to the inertial device costs less than a introduction, commonly used low precision inertial navigation equipment with tightly coupled GPS / INS integrated to get high precision navigation results. Many studies have improved the accuracy of error by using the UKF and CKF filtering algorithm, but it is still using the traditional pseudo code directly, the improvement effect is not obvious, and the disturbance is large. In this study, the PPP /INSmodel is improved by using the carrier phase smoothing pseudo range algorithm. Experimental results show that based on phase smoothing pseudo range PPP/INS tight coupled method, the position precision and the velocity precision for of the measured data of higher accuracy of MEMS and GPS receiver can get to a decimeter level and centimeter level. This coupling method has higher accuracy, stronger anti disturbance and Have a better convergence than the traditional C/A code. Based on different phase smoothing epoch number combination the accuracy and smoothing effect is also different, the larger smooth epoch number is, the better treatment effect it has and The higher precision it has. For high precision measurement, the equipment cost is saved. It has a practical significance meaning in the measurement of outdoor ground.

  16. Induction of anti-viral genes during acute infection with Viral hemorrhagic septicemia virus (VHSV) genogroup IVa in Pacific herring (Clupea pallasii)

    USGS Publications Warehouse

    Hansen, John D.; Woodson, James C.; Hershberger, Paul K.; Grady, Courtney; Gregg, Jacob L.; Purcell, Maureen K.

    2012-01-01

    Infection with the aquatic rhabdovirus Viral hemorrhagic septicemia virus (VHSV) genogroup IVa results in high mortality in Pacific herring (Clupea pallasii) and is hypothesized to be a potential limiting factor for herring recovery. To investigate anti-viral immunity in the Pacific herring, four immune response genes were identified: the myxovirus resistance (Clpa-Mx), a major histocompatibility complex IB (named Clpa-UAA.001), the inducible immunoproteosome subunit 9 (Clpa-PSMB9) and the neutrophil chemotactic factor (Clpa-LECT2). Reverse transcriptase quantitative PCR (RT-qPCR) assays were developed based on these gene sequences to investigate the host immune response to acute VHSV infection following both injection and immersion challenge. Virus levels were measured by both plaque assay and RT-qPCR and peaked at day 6 during the 10-day exposure period for both groups of fish. The interferon stimulated genes (Clpa-Mx, −UAA.001, and −PSMB9) were significantly up-regulated in response to VHSV infection at both 6 and 10 days post-infection in both spleen and fin. Results from this study indicate that Pacific herring mount a robust, early antiviral response in both fin and spleen tissues. The immunological tools developed in this study will be useful for future studies to investigate antiviral immunity in Pacific herring.

  17. Induction of anti-viral genes during acute infection with Viral hemorrhagic septicemia virus (VHSV) genogroup IVa in Pacific herring (Clupea pallasii).

    PubMed

    Hansen, John D; Woodson, James C; Hershberger, Paul K; Grady, Courtney; Gregg, Jacob L; Purcell, Maureen K

    2012-02-01

    Infection with the aquatic rhabdovirus Viral hemorrhagic septicemia virus (VHSV) genogroup IVa results in high mortality in Pacific herring (Clupea pallasii) and is hypothesized to be a potential limiting factor for herring recovery. To investigate anti-viral immunity in the Pacific herring, four immune response genes were identified: the myxovirus resistance (Clpa-Mx), a major histocompatibility complex IB (named Clpa-UAA.001), the inducible immunoproteosome subunit 9 (Clpa-PSMB9) and the neutrophil chemotactic factor (Clpa-LECT2). Reverse transcriptase quantitative PCR (RT-qPCR) assays were developed based on these gene sequences to investigate the host immune response to acute VHSV infection following both injection and immersion challenge. Virus levels were measured by both plaque assay and RT-qPCR and peaked at day 6 during the 10-day exposure period for both groups of fish. The interferon stimulated genes (Clpa-Mx, -UAA.001, and -PSMB9) were significantly up-regulated in response to VHSV infection at both 6 and 10 days post-infection in both spleen and fin. Results from this study indicate that Pacific herring mount a robust, early antiviral response in both fin and spleen tissues. The immunological tools developed in this study will be useful for future studies to investigate antiviral immunity in Pacific herring.

  18. Phase III Trial of Chemoradiotherapy for Anaplastic Oligodendroglioma: Long-Term Results of RTOG 9402

    PubMed Central

    Cairncross, Gregory; Wang, Meihua; Shaw, Edward; Jenkins, Robert; Brachman, David; Buckner, Jan; Fink, Karen; Souhami, Luis; Laperriere, Normand; Curran, Walter; Mehta, Minesh

    2013-01-01

    Purpose Anaplastic oligodendrogliomas, pure (AO) and mixed (anaplastic oligoastrocytoma [AOA]), are chemosensitive, especially if codeleted for 1p/19q, but whether patients live longer after chemoradiotherapy is unknown. Patients and Methods Eligible patients with AO/AOA were randomly assigned to procarbazine, lomustine, and vincristine (PCV) plus radiotherapy (RT) versus RT alone. The primary end point was overall survival (OS). Results Two hundred ninety-one eligible patients were randomly assigned: 148 to PCV plus RT and 143 to RT. For the entire cohort, there was no difference in median survival by treatment (4.6 years for PCV plus RT v 4.7 years for RT; hazard ratio [HR] = 0.79; 95% CI, 0.60 to 1.04; P = .1). Patients with codeleted tumors lived longer than those with noncodeleted tumors (PCV plus RT: 14.7 v 2.6 years, HR = 0.36, 95% CI, 0.23 to 0.57, P < .001; RT: 7.3 v 2.7 years, HR = 0.40, 95% CI, 0.27 to 0.60, P < .001), and the median survival of those with codeleted tumors treated with PCV plus RT was twice that of patients receiving RT (14.7 v 7.3 years; HR = 0.59; 95% CI, 0.37 to 0.95; P = .03). For those with noncodeleted tumors, there was no difference in median survival by treatment arm (2.6 v 2.7 years; HR = 0.85; 95% CI, 0.58 to 1.23; P = .39). In Cox models that included codeletion status, the adjusted OS for all patients was prolonged by PCV plus RT (HR = 0.67; 95% CI, 0.50 to 0.91; P = .01). Conclusion For the subset of patients with 1p/19q codeleted AO/AOA, PCV plus RT may be an especially effective treatment, although this observation was derived from an unplanned analysis. PMID:23071247

  19. The IAEA Coordinated Research Program on HTGR Uncertainty Analysis: Phase I Status and Initial Results

    SciTech Connect

    Strydom, Gerhard; Bostelmann, Friederike; Ivanov, Kostadin

    2014-10-01

    The continued development of High Temperature Gas Cooled Reactors (HTGRs) requires verification of HTGR design and safety features with reliable high fidelity physics models and robust, efficient, and accurate codes. One way to address the uncertainties in the HTGR analysis tools is to assess the sensitivity of critical parameters (such as the calculated maximum fuel temperature during loss of coolant accidents) to a few important input uncertainties. The input parameters were identified by engineering judgement in the past but are today typically based on a Phenomena Identification Ranking Table (PIRT) process. The input parameters can also be derived from sensitivity studies and are then varied in the analysis to find a spread in the parameter of importance. However, there is often no easy way to compensate for these uncertainties. In engineering system design, a common approach for addressing performance uncertainties is to add compensating margins to the system, but with passive properties credited it is not so clear how to apply it in the case of modular HTGR heat removal path. Other more sophisticated uncertainty modelling approaches, including Monte Carlo analysis, have also been proposed and applied. Ideally one wishes to apply a more fundamental approach to determine the predictive capability and accuracies of coupled neutronics/thermal-hydraulics and depletion simulations used for reactor design and safety assessment. Today there is a broader acceptance of the use of uncertainty analysis even in safety studies, and it has been accepted by regulators in some cases to replace the traditional conservative analysis. Therefore some safety analysis calculations may use a mixture of these approaches for different parameters depending upon the particular requirements of the analysis problem involved. Sensitivity analysis can for example be used to provide information as part of an uncertainty analysis to determine best estimate plus uncertainty results to the

  20. Drugs, Women and Violence in the Americas: U.S. Results of a Multi-Centric Pilot Project (Phase 1)

    PubMed Central

    González-Guarda, Rosa María; Peragallo, Nilda; Lynch, Ami; Nemes, Susanna

    2011-01-01

    Objectives To explore the collective and individual experiences that Latin American females in the U. S. have with substance abuse, violence and risky sexual behaviors. Methods This study was conducted in two phases that were carried out from July 2006 to June 2007 in south Florida. This paper covers Phase 1. In Phase 1, focus groups were conducted among 93 women in English, Spanish and Portuguese. Through content analyses of the focus group transcriptions, major themes were identified. Results Participants identified substance abuse, violence and risky sexual behaviors as closely related problems of great concern in Latina women in the U.S. Three important themes emerged from the focus groups. These included “Living in the US and the Devaluing of Latino Culture,” the “Vicious Cycle of Abuse” and “Breaking the Silence”. Conclusions The results from this study suggest that substance abuse, violence and HIV should be addressed in an integrative and comprehensive manner. Recommendations for the development of policies, programs and services addressing substance abuse, violence and risk for HIV among Latinos are provided. PMID:21593995

  1. Comparison of MDCT protocols in trauma patients with suspected splenic injury: superior results with protocol that includes arterial and portal venous phase imaging

    PubMed Central

    Melikian, Raymond; Goldberg, Stephanie; Strife, Brian James; Halvorsen, Robert A.

    2016-01-01

    PURPOSE We aimed to determine which intravenous contrast-enhanced multidetector computed tomography (MDCT) protocol produced the most accurate results for the detection of splenic vascular injury in hemodynamically stable patients who had sustained blunt abdominal trauma. METHODS We retrospectively reviewed 88 patients from 2003 to 2011 who sustained blunt splenic trauma and underwent contrast-enhanced MDCT and subsequent angiography. Results of MDCT scans utilizing single phase (portal venous only, n=8), dual phase (arterial + portal venous or portal venous + delayed, n=42), or triple phase (arterial + portal venous + delayed, n=38) were compared with results of subsequent splenic angiograms for the detection of splenic vascular injury. RESULTS Dual phase imaging was more sensitive and accurate than single phase imaging (P = 0.016 and P = 0.029, respectively). When the subsets of dual phase imaging were compared, arterial + portal venous phase imaging was more sensitive and accurate than portal venous + delayed phase imaging (P = 0.005 and P = 0.002, respectively). Triple phase imaging was more accurate (P = 0.015) than dual phase; however, when compared with the dual phase subset of arterial + portal venous, there was no statistical difference in either sensitivity or accuracy. CONCLUSION Our results support the use of dual phase contrast-enhanced MDCT, which includes the arterial phase, in patients with suspected splenic injury and question the utility of obtaining a delayed sequence. PMID:27334296

  2. Saturation of impurity-rich phases in a cerium-substituted pyrochlore-rich titanate ceramic: part 1 experimental results

    SciTech Connect

    Ryerson, F J; Ebbinghaus, B; Kirkorian, O; VanKonynenburg, R

    2000-05-25

    The saturation of impurity-rich accessory phases in a Ce-analog baseline ceramic formulation for the immobilization of excess plutonium has been tested by synthesizing an impurity-rich baseline compositions at 1300 C, 1350 C, and 1400 C in air. Impurity oxides are added at the 10 wt% level. The resulting phases assemblages are typically rich in pyrochlore, Hf-zirconolite (hafnolite), brannerite and rutile, but in many instances also contain an accessory mineral enriched in the impurity oxide. The concentration of that oxide in coexisting pyrochlore sets the saturation limit for solid solution of the component in question. In most cases, the accessory phase does not contain significant amounts of Ce, Gd or U. Exceptions are the stabilization of a Ca-lanthanide phosphate and a phosphate glass when P{sub 2}O{sub 5} is added to the formulation. P{sub 2}O{sub 5} addition is also very effective in reducing the modal amount of pyrochlore in the form relative to brannerite. Addition of the sodium-aluminosilicate, NaAlSiO{sub 4}, also results in the formation of a grain boundary melt at run conditions, but the fate of this phase on cooling is not well determined. At temperatures above 1300 C, addition of 10 wt% Fe{sub 2}O{sub 3} also leads to melting. Substitution of cations of different valences can also be associated with model-dependent changes in the oxidation state of uranium via charge transfer reactions. A set of simple components is suggested for the description of pyrochlores in both impurity-free and impurity-rich formulations.

  3. Does Concurrent Radiochemotherapy Affect Cosmetic Results in the Adjuvant Setting After Breast-Conserving Surgery? Results of the ARCOSEIN Multicenter, Phase III Study: Patients' and Doctors' Views

    SciTech Connect

    Toledano, Alain H. . E-mail: alain.toledano@gmail.com; Bollet, Marc A.; Fourquet, Alain; Azria, David; Gligorov, Joseph; Garaud, Pascal; Serin, Daniel; Bosset, Jean-Francois; Miny-Buffet, Joelle; Favre, Anne; Le Foch, Olivier; Calais, Gilles

    2007-05-01

    Purpose: To evaluate the cosmetic results of sequential vs. concurrent adjuvant chemotherapy with radiotherapy after breast-conserving surgery for breast cancer, and to compare ratings by patients and physicians. Methods and Materials: From 1996 to 2000, 716 patients with Stage I-II breast cancers were included in a multicenter, Phase III trial (the ARCOSEIN study) comparing, after breast-conserving surgery with axillary dissection, sequential treatment with chemotherapy first followed by radiotherapy vs. chemotherapy administered concurrently with radiotherapy. Cosmetic results with regard to both the overall aspect of the breast and specific changes (color, scar) were evaluated in a total of 214 patients (107 in each arm) by means of questionnaires to both the patient and a physician whose rating was blinded to treatment allocation. Results: Patients' overall satisfaction with cosmesis was not statistically different between the two arms, with approximately 92% with at least satisfactory results (p = 0.72), although differences between the treated and untreated breasts were greater after the concurrent regimen (29% vs. 14% with more than moderate differences; p 0.0015). Physician assessment of overall cosmesis was less favorable, with lower rates of at least satisfactory results in the concurrent arm (60% vs. 85%; p = 0.001). Consequently, the concordance for overall satisfaction with cosmesis between patients and doctors was only fair ({kappa} = 0.62). Conclusion: After breast-conserving surgery, the concurrent use of chemotherapy with radiotherapy is significantly associated with greater differences between the breasts. These differences do not translate into patients' lessened satisfaction with cosmesis.

  4. K1-95-HW, cruise report 1995: preliminary results. Phase III: sediment chemistry and biological sampling survey

    USGS Publications Warehouse

    Torresan, M.E.; Hampton, M.A.; Barber, J.H.; Wong, F.L.

    1995-01-01

    Mamala Bay, off the south shore of the island of Oahu, has been used as a repository of dredged material primarily from Pearl and Honolulu Harbors for over a century. The U.S. Geological Survey, U.S. Army Corps of Engineers, and the U.S. Environmental Protection Agency are conducting an integrated study on the distribution and character of dredged materials as well as the effects of dredged material on the marine environment. A three phase study is providing information to evaluate the effects on seafloor substrate and the benthic fauna. The studies include geophysical profiling and imaging, bottom photography, sampling, chemical and physical analyses of sediment, and evaluations of the benthic population, population density, and adverse impacts to the benthic fauna. Phase 1, conducted in 1993, inventoried the seafloor via remote sensing. Sidescan sonar and subbottom profilers characterized the seafloor in and around the disposal sites, and the resulting products reveal the character and extent of the dredged material. These data were used to plan Phase 2 in 1994, a sampling program that employed subbottom profilers, video and still photography, and seafloor sampling to ground truth the sonar mosaic and identify the seafloor substrates responsible for the various acoustic signatures on the sonar images and subbottom profiles. Box coring provided the samples necessary to distinguish dredged material from native sediment, and for the chemical analyses used to determine contaminant concentrations. Phase 3 studies conducted in June of 1995 consisted of box core sampling for chemical and biological analyses. Specific studies include: infaunal taxonomy and population density, bioassay/bioaccumulation, sediment chemistry, and post-disposal resuspension and transport. The 1995 survey, conducted June 14 through 17, resulted in the collection of 39 box cores from 20 different stations. Multiple box cores were composited at 7 different locations occupied in 1994, to provide

  5. Title IV-A Works Toward Total Child Development: John B. Gordon Elementary School, 1972-73. Research and Development Report, Volume 7, Number 25, December, 1973.

    ERIC Educational Resources Information Center

    McWilliams, Joyce H.; Wells, Veronica

    Gordon Elementary School had three supplementary programs during 1972-73 which were funded by federal, state, and local monies. Title IV-A is a federally funded program based on a "total family" approach to treating problems of the child and his education. Health, recreation, and physical fitness; remediation; family counseling; cultural…

  6. Thermal History of São João Nepomuceno (IVA) Iron Meteorite Inferred from Ganguly's Cooling Rate Model and 57Fe Mössbauer Spectroscopy Data

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    The intracrystalline Fe-Mg distribution in orthopyroxenes, as measured by means of 57Fe Mössbauer spectroscopy and associated to Ganguly’s cooling rate numerical method, are used to infer the thermal history of São João Nepomuceno (IVA) meteorite.

  7. A Description of the Structure, Functions, and Services of the Title IV-A Social Services Component in Philadelphia, 1974-1975. Report No. 7660.

    ERIC Educational Resources Information Center

    Asano, Mildred M.

    This report, representing the second half of a comprehensive study, presents descriptive data on the structure, functions, and services of the Social Services Component in Title IV-A Day Care in Philadelphia. Data were based on extensive interviews with 67 respondents representing 35 agencies. Two interviews, one each with a supervisor and a…

  8. A Profile of Social Service Personnel in Title IV-A Day Care in Philadelphia, 1974-1975. Report No. 7646.

    ERIC Educational Resources Information Center

    Asano, Mildred M.

    This report, representing the first half of a comprehensive study, describes the personnel of the Social Services Component in Title IV-A Day Care in Philadelphia and discusses some of the functions and services provided by these personnel. Data were based on responses from 129 service workers in 38 agencies. Respondents reported information on 21…

  9. Specific N-glycans of Hepatocellular Carcinoma Cell Surface and the Abnormal Increase of Core-α-1, 6-fucosylated Triantennary Glycan via N-acetylglucosaminyltransferases-IVa Regulation.

    PubMed

    Nie, Huan; Liu, Xia; Zhang, Yubao; Li, Tingting; Zhan, Chao; Huo, Wenjuan; He, Anshun; Yao, Yuanfei; Jin, Yu; Qu, Youpeng; Sun, Xue-Long; Li, Yu

    2015-11-05

    Glycosylation alterations of cell surface proteins are often observed during the progression of malignancies. The specific cell surface N-glycans were profiled in hepatocellular carcinoma (HCC) with clinical tissues (88 tumor and adjacent normal tissues) and the corresponding serum samples of HCC patients. The level of core-α-1,6-fucosylated triantennary glycan (NA3Fb) increased both on the cell surface and in the serum samples of HCC patients (p < 0.01). Additionally, the change of NA3Fb was not influenced by Hepatitis B virus (HBV)and cirrhosis. Furthermore, the mRNA and protein expression of N-acetylglucosaminyltransferase IVa (GnT-IVa), which was related to the synthesis of the NA3Fb, was substantially increased in HCC tissues. Knockdown of GnT-IVa leads to a decreased level of NA3Fb and decreased ability of invasion and migration in HCC cells. NA3Fb can be regarded as a specific cell surface N-glycan of HCC. The high expression of GnT-IVa is the cause of the abnormal increase of NA3Fb on the HCC cell surface, which regulates cell migration. This study demonstrated the specific N-glycans of the cell surface and the mechanisms of altered glycoform related with HCC. These findings lead to better understanding of the function of glycan and glycosyltransferase in the tumorigenesis, progression and metastasis of HCC.

  10. A Description of Room Arrangement, Design, and Appearance in Title IV-A Day Care Centers in Philadelphia, 1974-1975. Report No. 7733.

    ERIC Educational Resources Information Center

    Silber, Theodore J.

    This report describes the room arrangement, design, and appearance of 152 Title IV-A Day Care centers in Philadelphia. A series of 27 items on a section of the Daily Care, In-Room Observation Guide was used to provide an overall description of rooms in day care and to identify differences in features for different types of programs. Data were…

  11. Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer

    ClinicalTrials.gov

    2016-02-09

    Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer

  12. The Controls-Structures Interaction Guest Investigator Program - An overview and phase I experimental results. [for flexible spacecraft

    NASA Technical Reports Server (NTRS)

    Smith-Taylor, Rudeen; Tanner, Sharon E.

    1991-01-01

    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 I 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: 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.

  13. OECD/NEA expert group on uncertainty analysis for criticality safety assessment: Results of benchmark on sensitivity calculation (phase III)

    SciTech Connect

    Ivanova, T.; Laville, C.; Dyrda, J.; Mennerdahl, D.; Golovko, Y.; Raskach, K.; Tsiboulia, A.; Lee, G. S.; Woo, S. W.; Bidaud, A.; Sabouri, P.; Bledsoe, K.; Rearden, B.; Gulliford, J.; Michel-Sendis, F.

    2012-07-01

    The sensitivities of the k{sub eff} eigenvalue to neutron cross sections have become commonly used in similarity studies and as part of the validation algorithm for criticality safety assessments. To test calculations of the sensitivity coefficients, a benchmark study (Phase III) has been established by the OECD-NEA/WPNCS/EG UACSA (Expert Group on Uncertainty Analysis for Criticality Safety Assessment). This paper presents some sensitivity results generated by the benchmark participants using various computational tools based upon different computational methods: SCALE/TSUNAMI-3D and -1D, MONK, APOLLO2-MORET 5, DRAGON-SUSD3D and MMKKENO. The study demonstrates the performance of the tools. It also illustrates how model simplifications impact the sensitivity results and demonstrates the importance of 'implicit' (self-shielding) sensitivities. This work has been a useful step towards verification of the existing and developed sensitivity analysis methods. (authors)

  14. The National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC): Results from Phase I and Scientific Opportunities in Phase II

    PubMed Central

    Kroner, Barbara L.; Tolunay, H. Eser; Basson, Craig T.; Pyeritz, Reed E.; Holmes, Kathryn; Maslen, Cheryl L.; Milewicz, Dianna M.; LeMaire, Scott A.; Hendershot, Tabitha; Desvigne-Nickens, Patrice; Devereux, Richard B.; Dietz, Harry C.; Song, Howard; Ringer, Danny; Mitchell, Megan; Weinsaft, Jonathan W.; Ravekes, William; Menashe, Victor; Eagle, Kim A.

    2011-01-01

    Background Genetically triggered thoracic aortic conditions (GenTAC) represent an important problem for patients and their families. Accordingly, the National Heart, Lung and Blood Institute (NHLBI) established the first phase of its national GenTAC Registry in 2006. Enrollment and Diagnoses Between 2007 and 2010, six enrolling centers established the GenTAC I Registry consisting of 2,046 patients [(Marfan syndrome 576 (28.2%); bicuspid aortic valve disease 504 (24.6%), aneurysm or dissection age <50 years 369 (18%), and others.] Biologic samples for DNA analyses (WBC’s or saliva) are available in 97% and stored plasma is available in 60% of enrollees. Results Initial scientific inquiry using the GenTAC Registry has included validation studies of genetic causes for aortic syndromes, potential usefulness of TGFB blood levels in Marfan subjects, and current surgical approaches to ascending aortic conditions. Future Opportunity GenTAC II will allow biannual follow-up of GenTAC I enrollees for up to nine years, enrollment of an additional 1,500 subjects, further integration of imaging findings with clinical and genetic data through utilization of an imaging core lab, important validation of phenotype-genotype correlations through a phenotyping core lab, and integration of a scientific advisory committee to help define the full range and depth of the Registry’s scientific capabilities. The registry resources are available to the external scientific community through an application process accessible at https://gentac.rti.org. PMID:21982653

  15. High and low pressure phase equilibria of a mildly alkalic lava from the 1965 Surtsey eruption: Experimental results

    NASA Astrophysics Data System (ADS)

    Thy, P.

    1991-01-01

    Melting experiments have been performed on a primitive, mildly alkalic glassy lava (10 wt.% MgO) from the 1965 eruption of the Surtsey volcano located at the tip of the south-eastern propagating rift zone of Iceland. At atmospheric pressure, approximately on the FMQ oxygen buffer, olivine (Fo 81) crystallizes from 1240°C, followed by plagioclase (An 70) from 1180°C and augite from 1140°C. The experimental glasses coexisting with olivine, plagioclase and augite are ferrobasaltic enriched in FeO (13.6-14.2 wt.%) and TiO 2 (4.0-4.4 wt.%). In high pressure, piston-cylinder, graphite-controlled runs, olivine occurs as the liquidus phase until 14 kbar, above which augite is the liquidus phase. Low-Ca pyroxene is not a liquidus phase at any pressure. The high pressure liquids are, relative to the one atmosphere liquids, significantly enriched in Al 2O 3 and Na 2O and depleted in CaO as a result of changes in the crystallizing assemblages. Furthermore, liquidus augite is dominantly subcalcic and shows significant enrichment in Al and depletion in Ti. Subliquidus plagioclase is enriched in sodium relative to low pressure phase compositions. Evaluated in normative projections, contrasting liquid lines of descent are revealed as a function of pressure. At one atmosphere, the multisaturated liquids are located close to the thermal divide defined by the plane olivine-plagioclase-augite, but appear, with advanced degrees of crystallization, to be moving away from the thermal divide toward normative quartz. The augites crystallizing in the one atmosphere experiments are calcic and slightly nepheline normative. In the 10 and 12.5 kbar experiments, the augites become subcalcic and dominantly hypersthene normative. Because of this shift in augite compositions, transitional basaltic liquids may at high pressure evolve from the tholeiitic side of the olivine-plagioclase-diopside normative divide onto the alkalic side. With increasing pressure above 15 kbar, the liquidus augite

  16. Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study

    PubMed Central

    Hochhaus, A; Rosti, G; Cross, N C P; Steegmann, J L; le Coutre, P; Ossenkoppele, G; Petrov, L; Masszi, T; Hellmann, A; Griskevicius, L; Wiktor-Jedrzejczak, W; Rea, D; Coriu, D; Brümmendorf, T H; Porkka, K; Saglio, G; Gastl, G; Müller, M C; Schuld, P; Di Matteo, P; Pellegrino, A; Dezzani, L; Mahon, F-X; Baccarani, M; Giles, F J

    2016-01-01

    The Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study included 1089 patients with newly diagnosed chronic myeloid leukemia in chronic phase. The rate of deep molecular response (MR4 (BCR-ABL1⩽0.01% on the International Scale or undetectable BCR-ABL1 with ⩾10 000 ABL1 transcripts)) at 18 months was evaluated as the primary end point, with molecular responses monitored by the European Treatment and Outcome Study network of standardized laboratories. This analysis was conducted after all patients had completed 24 months of study treatment (80.9% of patients) or discontinued early. In patients with typical BCR-ABL1 transcripts and ⩽3 months of prior imatinib therapy, 38.4% (404/1052) achieved MR4 at 18 months. Six patients (0.6%) developed accelerated or blastic phase, and 13 (1.2%) died. The safety profile of nilotinib was consistent with that of previous studies, although the frequencies of some nilotinib-associated adverse events were lower (for example, rash, 21.4%). Ischemic cardiovascular events occurred in 6.0% of patients. Routine monitoring of lipid and glucose levels was not mandated in the protocol. These results support the use of frontline nilotinib, particularly when achievement of a deep molecular response (a prerequisite for attempting treatment-free remission in clinical trials) is a treatment goal. PMID:26437782

  17. First Results from the RPC Magnetometer Experiment during the Approach Phase to 67P/Churyumov-Gerasimenko

    NASA Astrophysics Data System (ADS)

    Richter, I.; Glassmeier, K. H.; Koenders, C.; Carr, C.; Cupido, E.; Vallat, C.; Motschmann, U. M.; Tsurutani, B. T.; Volwerk, M.

    2014-12-01

    The European Space Agency's spacecraft ROSETTA has reached its final destination, the comet 67P/Churyumov-Gerasimenko. The ROSETTA orbiter is equipped with a complete plasma package named RPC (ROSETTA Plasma Consortium). Included is the magnetometer system RPC-MAG which consists of 2 triaxial Fluxgate magnetometers located on a 1.5 m long boom outside the spacecraft. During the approach phase to the comet magnetic field measurements have been performed since May 2014. We will report on these measurements showing the evolution of the magnetic field from the solar wind dominated to a cometary influenced plasma. A detailed discussion of the observed signatures will be presented in order to separate spacecraft generated disturbances from real cometary signals. The very first results of the magnetic field measurements will be compared with theoretically expected structures.

  18. Odour reduction strategies for biosolids produced from a Western Australian wastewater treatment plant: results from Phase I laboratory trials.

    PubMed

    Gruchlik, Yolanta; Heitz, Anna; Joll, Cynthia; Driessen, Hanna; Fouché, Lise; Penney, Nancy; Charrois, Jeffrey W A

    2013-01-01

    This study investigated sources of odours from biosolids produced from a Western Australian wastewater treatment plant and examined possible strategies for odour reduction, specifically chemical additions and reduction of centrifuge speed on a laboratory scale. To identify the odorous compounds and assess the effectiveness of the odour reduction measures trialled in this study, headspace solid-phase microextraction gas chromatography-mass spectrometry (HS SPME-GC-MS) methods were developed. The target odour compounds included volatile sulphur compounds (e.g. dimethyl sulphide, dimethyl disulphide and dimethyl trisulphide) and other volatile organic compounds (e.g. toluene, ethylbenzene, styrene, p-cresol, indole and skatole). In our laboratory trials, aluminium sulphate added to anaerobically digested sludge prior to dewatering offered the best odour reduction strategy amongst the options that were investigated, resulting in approximately 40% reduction in the maximum concentration of the total volatile organic sulphur compounds, relative to control. PMID:24355840

  19. Research on an expert system for database operation of simulation-emulation math models. Volume 1, Phase 1: Results

    NASA Technical Reports Server (NTRS)

    Kawamura, K.; Beale, G. O.; Schaffer, J. D.; Hsieh, B. J.; Padalkar, S.; Rodriguez-Moscoso, J. J.

    1985-01-01

    The results of the first phase of Research on an Expert System for Database Operation of Simulation/Emulation Math Models, is described. Techniques from artificial intelligence (AI) were to bear on task domains of interest to NASA Marshall Space Flight Center. One such domain is simulation of spacecraft attitude control systems. Two related software systems were developed to and delivered to NASA. One was a generic simulation model for spacecraft attitude control, written in FORTRAN. The second was an expert system which understands the usage of a class of spacecraft attitude control simulation software and can assist the user in running the software. This NASA Expert Simulation System (NESS), written in LISP, contains general knowledge about digital simulation, specific knowledge about the simulation software, and self knowledge.

  20. Clinical Results of Real-Time Ultrasonic Scanning of the Heart Using a Phased Array System 12

    PubMed Central

    Kisslo, Joseph A.; Vonramm, Olaf T.; Thurstone, Frederick 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. ImagesFIG. 5FIG. 6FIG. 7FIG. 8FIG. 9FIG. 10FIG. 11 PMID:906555

  1. Summary Report on Phase I Results from the 3D Printing in Zero G Technology Demonstration Mission, Volume I

    NASA Technical Reports Server (NTRS)

    Prater, T. J.; Bean, Q. A.; Beshears, R. D.; Rolin, T. D.; Werkheiser, N. J.; Ordonez, E. A.; Ryan, R. M.; Ledbetter, F. E., III

    2016-01-01

    Human space exploration to date has been confined to low-Earth orbit and the Moon. The International Space Station (ISS) provides a unique opportunity for researchers to prove out the technologies that will enable humans to safely live and work in space for longer periods of time and venture beyond the Earth/Moon system. The ability to manufacture parts in-space rather than launch them from Earth represents a fundamental shift in the current risk and logistics paradigm for human spaceflight. In September 2014, NASA, in partnership with Made In Space, Inc., launched the 3D Printing in Zero-G technology demonstration mission to explore the potential of additive manufacturing for in-space applications and demonstrate the capability to manufacture parts and tools on orbit using fused deposition modeling. This Technical Publication summarizes the results of testing to date of the ground control and flight prints from the first phase of this ISS payload.

  2. High-pressure phases of a hydrogen-rich compound: Tetramethylgermane

    NASA Astrophysics Data System (ADS)

    Qin, Zhen-Xing; Zhang, Chao; Tang, Ling-Yun; Zhong, Guo-Hua; Lin, Hai-Qing; Chen, Xiao-Jia

    2012-11-01

    The vibrational and structural properties of a hydrogen-rich group IVa hydride, Ge(CH3)4, are studied by combining Raman spectroscopy and synchrotron x-ray diffraction measurements at room temperature and at pressures up to 30.2 GPa. Both techniques allow the obtaining of complementary information on the high-pressure behaviors and yield consistent phase transitions at 1.4 GPa for the liquid to solid and 3.0, 5.4, and 20.3 GPa for the solid to solid. The four high-pressure solid phases are identified to have the cubic, orthorhombic, monoclinic, and monoclinic crystal structures with space groups of Pa-3 for phase I, Pnma for phase II, P21/c for phase III, and P21 for phase IV, respectively. These transitions are suggested to result from the changes in the inter- and intramolecular bonding of this compound. The softening of some Raman modes on CH3 groups and their sudden disappearance indicate that Ge(CH3)4 might be an ideal compound to realize metallization and even high-temperature superconductivity at modest static pressure for laboratory capability.

  3. 30 CFR 203.40 - Which leases are eligible for royalty relief as a result of drilling a deep well or a phase 1...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REDUCTION IN ROYALTY RATES OCS Oil, Gas, and Sulfur General Royalty Relief for Drilling Deep Gas Wells on... a result of drilling a deep well or a phase 1 ultra-deep well? 203.40 Section 203.40 Mineral... a result of drilling a deep well or a phase 1 ultra-deep well? Your lease may receive an RSV...

  4. 30 CFR 203.40 - Which leases are eligible for royalty relief as a result of drilling a deep well or a phase 1...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... a result of drilling a deep well or a phase 1 ultra-deep well? 203.40 Section 203.40 Mineral... Relief for Drilling Deep Gas Wells on Leases Not Subject to Deep Water Royalty Relief § 203.40 Which leases are eligible for royalty relief as a result of drilling a deep well or a phase 1 ultra-deep...

  5. 30 CFR 203.40 - Which leases are eligible for royalty relief as a result of drilling a deep well or a phase 1...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... a result of drilling a deep well or a phase 1 ultra-deep well? 203.40 Section 203.40 Mineral... eligible for royalty relief as a result of drilling a deep well or a phase 1 ultra-deep well? Your lease... of 87 degrees, 30 minutes West longitude in water depths entirely less than 400 meters deep. (b)...

  6. Phase IIB/III Trial of Tenecteplase in Acute Ischemic Stroke: Results of a Prematurely Terminated Randomized Clinical Trial

    PubMed Central

    Haley, E. Clarke; Thompson, John L.P.; Grotta, James C.; Lyden, Patrick D.; Hemmen, Thomas G.; Brown, Devin L.; Fanale, Christopher; Libman, Richard; Kwiatkowski, Thomas G.; Llinas, Rafael H.; Levine, Steven R.; Johnston, Karen C.; Buchsbaum, Richard; Levy, Gilberto; Levin, Bruce

    2010-01-01

    Background: Intravenous alteplase (rt-PA) remains the only approved treatment for acute ischemic stroke, but its use remains limited. In a previous pilot dose-escalation study, intravenous tenecteplase showed promise as a potentially safer alternative. Therefore, a Phase IIB clinical trial was begun to a) choose a best dose of tenecteplase to carry forward, and b) to provide evidence for either promise or futility of further testing of tenecteplase versus rt-PA. If promise was established, then the trial would continue as a Phase III efficacy trial comparing the selected tenecteplase dose to standard rt-PA. Methods: The trial began as a small, multi-center, randomized, double-blind, controlled clinical trial comparing 0.1, 0.25, and 0.4 mg/kg tenecteplase with standard 0.9 mg/kg rt-PA in patients with acute stroke within 3 hours of onset. An adaptive sequential design used an early (24 hour) assessment of major neurological improvement balanced against occurrence of symptomatic intracranial hemorrhage (ICH) to choose a “best” dose of tenecteplase to carry forward. Once a “best” dose was established, the trial was to continue until at least 100 pairs of the selected tenecteplase dose versus standard rt-PA could be compared by 3 month outcome using the modified Rankin Scale in an interim analysis. Decision rules were devised to yield a clear recommendation to either stop for futility or to continue into Phase III. Results: The trial was prematurely terminated for slow enrollment after only 112 patients had been randomized at 8 clinical centers between 2006 and 2008. The 0.4 mg/kg dose was discarded as inferior after only 73 patients were randomized, but the selection procedure was still unable to distinguish between 0.1 mg/kg and 0.25 mg/kg as a propitious dose at the time the trial was stopped. There were no statistically persuasive differences in 3 month outcomes between the remaining tenecteplase groups and rt-PA. Symptomatic ICH rates were highest in the

  7. An adaptive microwave phased array for targeted heating of deep tumours in intact breast: animal study results.

    PubMed

    Fenn, A J; Wolf, G L; Fogle, R M

    1999-01-01

    It has previously been reported in phantoms, that an adaptive radiofrequency phased array can generate deep focused heating distributions without overheating the skin and superficial healthy tissues. The present study involves adaptive microwave phased array hyperthermia tests in animals (rabbits) with and without tumours. The design of the adaptive phased array as applied to the treatment of tumours in intact breast, is described. The adaptive phased array concept uses breast compression and dual-opposing 915 MHz air-cooled waveguide applicators with electronic phase shifters and electric-field feedback, to focus automatically by computer control the microwave radiation in deep tissue. Temperature measurements for a clinical adaptive phased array hyperthermia system demonstrate tissue heating at depth with reduced skin heating.

  8. Results of the Phase I Dose-Escalating Study of Motexafin Gadolinium With Standard Radiotherapy in Patients With Glioblastoma Multiforme

    SciTech Connect

    Ford, Judith M. Seiferheld, Wendy; Alger, Jeffrey R.; Wu, Genevieve; Endicott, Thyra J.; Mehta, Minesh; Curran, Walter; Phan, See-Chun

    2007-11-01

    Purpose: Motexafin gadolinium (MGd) is a putative radiation enhancer initially evaluated in patients with brain metastases. This Phase I trial studied the safety and tolerability of a 2-6-week course (10-22 doses) of MGd with radiotherapy for glioblastoma multiforme. Methods and Materials: A total of 33 glioblastoma multiforme patients received one of seven MGd regimens starting at 10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10 daily doses then three times per week). The National Cancer Institute Cancer Therapy Evaluation Program toxicity and stopping rules were applied. Results: The maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times per week) for 22 doses. The dose-limiting toxicity was reversible transaminase elevation. Adverse reactions included rash/pruritus (45%), chills/fever (30%), and self-limiting vesiculobullous rash of the thumb and fingers (42%). The median survival of 17.6 months prompted a case-matched analysis. In the case-matched analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared with the matched Radiation Therapy Oncology Group database patients with a median survival of 11.8 months (hazard ratio, 0.43; 95% confidence interval, 0.20-0.94). Conclusion: The maximal tolerated dose of MGd with radiotherapy for glioblastoma multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then three times weekly). The baseline survival calculations suggest progression to Phase II trials is appropriate, with the addition of MGd to radiotherapy with concurrent and adjuvant temozolomide.

  9. Intravitreal Sirolimus for the Treatment of Geographic Atrophy: Results of a Phase I/II Clinical Trial

    PubMed Central

    Petrou, Philip A.; Cunningham, Denise; Shimel, Katherine; Harrington, Molly; Hammel, Keri; Cukras, Catherine A.; Ferris, Frederick L.; Chew, Emily Y.; Wong, Wai T.

    2015-01-01

    Purpose. To investigate the safety and effects of intravitreal sirolimus for the potential treatment of geographic atrophy (GA). Methods. The study was a single-center, open-label, phase I/II trial enrolling six participants with bilateral GA treated with intravitreal sirolimus in only one randomly assigned eye, with the fellow eye as control. The primary efficacy outcome measure was the change in total GA area from baseline on color fundus photography (CFP); secondary outcomes included changes in GA area on fundus autofluorescence (FAF), visual acuity, central retinal thickness (CRT), and macular sensitivity from baseline. Results. Although no systemic adverse events were attributed to treatment, two of six participants had ocular adverse events that were possibly associated. The treated eye of one participant developed abnormal paralesional changes on FAF that were associated with accelerated retinal thinning. This accelerated retinal thinning was also seen in the treated eye of a second participant. Because of concern that these events were associated with treatment, treatment was suspended. Comparisons of treated and fellow eyes for change in visual acuity, change in GA area, and change in CRT showed no evidence of treatment benefit and generally favored the untreated fellow eye. Conclusions. While paralesional FAF changes and rapid retinal thinning observed are potentially part of the natural course of GA, they may possibly be related to treatment. No general evidence of anatomical or functional benefit was detected in treated eyes. Further data on intravitreal sirolimus for GA treatment will be available from a larger phase II trial. (ClinicalTrials.gov number, NCT01445548.) PMID:25525171

  10. Gas tracer transport in a heterogeneous fracture in two-phase flow conditions. Experimental and modeling results

    NASA Astrophysics Data System (ADS)

    Jódar, Jorge; Medina, Agustín; Carrera, Jesús

    2011-11-01

    Large amounts of gas can result from anaerobic corrosion of metals and from chemical and biological degradation of organic substances in underground repositories for radioactive waste. Gas generation may lead to the formation of a buoyant gas phase bubble (i.e. zone with increased gas saturation surrounded by water) and to the migration of radioactive gaseous species. In this situation, gaseous species migration is controlled by (1) advection, dispersion and diffusion within the gas bubble, and (2) dissolution in the water surrounding the gas bubble and diffusion of the dissolved species away from the interface. A number of gas tracer tests were performed in the framework of the GAs Migration (GAM) project to study the role played by dissolution/diffusion phenomena in gas transport. Tracers were selected to display a large range of solubility and diffusion coefficients, which should have led to significant chromatographic separation in the breakthrough curves (BTCs) of the tracers. However, measured BTCs displayed much smaller chromatographic separation than expected. These curves were interpreted using (1) a numerical model of multiphase flow and tracer transport in the fracture plane and diffusion into the immobile water, and (2) a simple two box model. Results showed that dissolution/diffusion into immobile water regions played a small role, and tailing appears to have been largely controlled by diffusion into dead gas volumes, such as boreholes.

  11. Results on neutrinoless double-β decay of 76Ge from phase I of the GERDA experiment.

    PubMed

    Agostini, M; Allardt, M; Andreotti, E; Bakalyarov, A M; Balata, M; Barabanov, I; Barnabé Heider, M; Barros, N; Baudis, L; Bauer, C; Becerici-Schmidt, N; Bellotti, E; Belogurov, S; Belyaev, S T; Benato, G; Bettini, A; Bezrukov, L; Bode, T; Brudanin, V; Brugnera, R; Budjáš, D; Caldwell, A; Cattadori, C; Chernogorov, A; Cossavella, F; Demidova, E V; Domula, A; Egorov, V; Falkenstein, R; Ferella, A; Freund, K; Frodyma, N; Gangapshev, A; Garfagnini, A; Gotti, C; Grabmayr, P; Gurentsov, V; Gusev, K; Guthikonda, K K; Hampel, W; Hegai, A; Heisel, M; Hemmer, S; Heusser, G; Hofmann, W; Hult, M; Inzhechik, L V; Ioannucci, L; Janicskó Csáthy, J; Jochum, J; Junker, M; Kihm, T; Kirpichnikov, I V; Kirsch, A; Klimenko, A; 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; Liu, X; Lubashevskiy, A; Lubsandorzhiev, B; Lutter, G; Macolino, C; Machado, A A; Majorovits, B; Maneschg, W; Misiaszek, M; Nemchenok, I; Nisi, S; O'Shaughnessy, C; Pandola, L; Pelczar, K; Pessina, G; Pullia, A; Riboldi, S; Rumyantseva, N; Sada, C; Salathe, M; Schmitt, C; Schreiner, J; Schulz, O; Schwingenheuer, B; Schönert, S; Shevchik, E; Shirchenko, M; Simgen, H; Smolnikov, A; Stanco, L; Strecker, H; Tarka, M; Ur, C A; Vasenko, A A; Volynets, O; von Sturm, K; Wagner, V; Walter, M; Wegmann, A; Wester, T; Wojcik, M; Yanovich, E; Zavarise, P; Zhitnikov, I; Zhukov, S V; Zinatulina, D; Zuber, K; Zuzel, G

    2013-09-20

    Neutrinoless double beta decay is a process that violates lepton number conservation. It is predicted to occur in extensions of the standard model of particle physics. This Letter reports the results from phase I of the Germanium Detector Array (GERDA) experiment at the Gran Sasso Laboratory (Italy) searching for neutrinoless double beta decay of the isotope (76)Ge. Data considered in the present analysis have been collected between November 2011 and May 2013 with a total exposure of 21.6 kg yr. A blind analysis is performed. The background index is about 1 × 10(-2) counts/(keV kg yr) after pulse shape discrimination. No signal is observed and a lower limit is derived for the half-life of neutrinoless double beta decay of (76)Ge, T(1/2)(0ν) >2.1 × 10(25) yr (90% C.L.). The combination with the results from the previous experiments with (76)Ge yields T(1/2)(0ν)>3.0 × 10(25) yr (90% C.L.).

  12. First results of a large-area cryogenic gaseous photomultiplier coupled to a dual-phase liquid xenon TPC

    NASA Astrophysics Data System (ADS)

    Arazi, L.; Coimbra, A. E. C.; Erdal, E.; Israelashvili, I.; Rappaport, M. L.; Shchemelinin, S.; Vartsky, D.; dos Santos, J. M. F.; Breskin, A.

    2015-10-01

    We discuss recent advances in the development of cryogenic gaseous photomultipliers (GPM), for possible use in dark matter and other rare-event searches using noble-liquid targets. We present results from a 10 cm diameter GPM coupled to a dual-phase liquid xenon (LXe) TPC, demonstrating—for the first time—the feasibility of recording both primary (``S1'') and secondary (``S2'') scintillation signals. The detector comprised a triple Thick Gas Electron Multiplier (THGEM) structure with cesium iodide photocathode on the first element; it was shown to operate stably at 180 K with gains above 105, providing high single-photon detection efficiency even in the presence of large α particle-induced S2 signals comprising thousands of photoelectrons. S1 scintillation signals were recorded with a time resolution of 1.2 ns (RMS). The energy resolution (σ/E) for S2 electroluminescence of 5.5 MeV α particles was ~ 9%, which is comparable to that obtained in the XENON100 TPC with PMTs. The results are discussed within the context of potential GPM deployment in future multi-ton noble-liquid detectors.

  13. The InterFrost benchmark of Thermo-Hydraulic codes for cold regions hydrology - first inter-comparison phase results

    NASA Astrophysics Data System (ADS)

    Grenier, Christophe; Rühaak, Wolfram

    2016-04-01

    are essentially theoretical but include the full complexity of the coupled non-linear set of equations (heat transfer with conduction, advection, phase change and Darcian flow). The complete set of inter-comparison results shows that the participating codes all produce simulations which are quantitatively similar and correspond to physical intuition. From a quantitative perspective, they agree well over the whole set of performance measures. The differences among the simulation results will be discussed in more depth throughout the test cases especially for the identification of the threshold times for each system as these exhibited the least agreement. However, the results suggest that in spite of the difficulties associated with the resolution of the set of TH equations (coupled and non-linear structure with phase change providing steep slopes), the developed codes provide robust results with a qualitatively reasonable representation of the processes and offer a quantitatively realistic basis. Further perspectives of the exercise will also be presented.

  14. Amyloid-β 11C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials

    PubMed Central

    Schmidt, Mark E.; Margolin, Richard; Sperling, Reisa; Koeppe, Robert; Mason, Neale S.; Klunk, William E.; Mathis, Chester A.; Salloway, Stephen; Fox, Nick C.; Hill, Derek L.; Les, Andrea S.; Collins, Peter; Gregg, Keith M.; Di, Jianing; Lu, Yuan; Tudor, I. Cristina; Wyman, Bradley T.; Booth, Kevin; Broome, Stephanie; Yuen, Eric; Grundman, Michael; Brashear, H. Robert

    2015-01-01

    Objective: To evaluate the effects of bapineuzumab on brain β-amyloid (Aβ) burden using 11C-Pittsburgh compound B (11C-PiB)-PET. Methods: Two phase 3 clinical trials, 1 each in apolipoprotein APOE ε4 carriers and noncarriers, were conducted in patients with mild to moderate Alzheimer disease dementia. Bapineuzumab, an anti-Aβ monoclonal antibody, or placebo, was administered by IV infusion every 13 weeks for 78 weeks. PET substudies assessed change in brain fibrillar Aβ over 71 weeks using an 11C-PiB-PET standardized uptake value ratio (SUVr) global cortical average (GCA) comprising the average SUVr from 5 cortical regions of interest with cerebellar gray matter as the reference region. Results: A total of 115 carriers and 39 noncarriers were analyzed. The difference (δ) in mean baseline to 71 week change in 11C-PiB-PET GCA between bapineuzumab and placebo was significant in carriers (0.5 mg/kg vs placebo δ = −0.101; p = 0.004) and in pooled analyses of both carriers and noncarriers (0.5 mg/kg vs placebo δ = −0.068; p = 0.027; 1.0 mg/kg vs placebo δ = −0.133; p = 0.028) but not in the noncarrier trial separately. Analyses by individual region of interest and in mild disease yielded findings similar to the main trial results. Conclusions: The 11C-PiB-PET imaging results demonstrated reduction of fibrillar Aβ accumulation in patients with Alzheimer disease treated with bapineuzumab; however, as no clinical benefit was observed, the findings are consistent with the hypotheses that bapineuzumab may not have been initiated early enough in the disease course, the doses were insufficient, or the most critical Aβ species were inadequately targeted. PMID:26208959

  15. Psychosocial Results from a Phase I Trial of a Nonsurgical Circumcision Device for Adult Men in Zimbabwe.

    PubMed

    Kasprzyk, Danuta; Montaño, Daniel E; Hamilton, Deven T; Down, Kayla L; Marrett, Karl D; Tshimanga, Mufuta; Xaba, Sinokuthemba; Mugurungi, Owen

    2016-01-01

    Male circumcision (MC), an effective HIV prevention tool, has been added to Zimbabwe's Ministry of Health and Child Care HIV/AIDS Prevention Program. A Phase I safety trial of a nonsurgical male circumcision device was conducted and extensive psychosocial variables were assessed. Fifty-three men (18 and older) were recruited for the device procedure; 13 follow-up clinical visits were completed. Interviews conducted three times (before the procedure, at 2 weeks and 90 days post-procedure) assessed: Satisfaction; expectations; actual experience; activities of daily living; sexual behavior; and HIV risk perception. Using the Integrated Behavioral Model, attitudes towards MC, sex, and condoms, and sources of social influence and support were also assessed. Men (mean age 32.5, range 18-50; mean years of education = 13.6; 55% employed) were satisfied with device circumcision results. Men understand that MC is only partially protective against HIV acquisition. Most (94.7%) agreed that they will continue to use condoms to protect themselves from HIV. Pain ratings were surprisingly negative for a procedure billed as painless. Men talked to many social networks members about their MC experience; post-procedure (mean of 14 individuals). Minimal impact on activities of daily living and absenteeism indicate possible cost savings of device circumcisions. Spontaneous erections occurred frequently post-procedure. The results had important implications for changes in the pre-procedure clinical counseling protocol. Clear-cut counseling to manage pain and erection expectations should result in improved psychosocial outcomes in future roll-out of device circumcisions. Men's expectations must be managed through evidence-based counseling, as they share their experiences broadly among their social networks. PMID:26745142

  16. Effect of the application of an electric field on the performance of a two-phase loop device: preliminary results

    NASA Astrophysics Data System (ADS)

    Creatini, F.; Di Marco, P.; Filippeschi, S.; Fioriti, D.; Mameli, M.

    2015-11-01

    In the last decade, the continuous development of electronics has pointed out the need for a change in mind with regard to thermal management. In the present scenario, Pulsating Heat Pipes (PHPs) are novel promising two-phase passive heat transport devices that seem to meet all present and future thermal requirements. Nevertheless, PHPs governing phenomena are quite unique and not completely understood. In particular, single closed loop PHPs manifest several drawbacks, mostly related to the reduction of device thermal performance and reliability, i.e. the occurrence of multiple operational quasi-steady states. The present research work proposes the application of an electric field as a technique to promote the circulation of the working fluid in a preferential direction and stabilize the device operation. The tested single closed loop PHP is made of a copper tube with an inner tube diameter equal to 2.00 mm and filled with pure ethanol (60% filling ratio). The electric field is generated by a couple of wire-shaped electrodes powered with DC voltage up to 20 kV and laid parallel to the longitudinal axis of the glass tube constituting the adiabatic section. Although the electric field intensity in the working fluid region is weakened both by the polarization phenomenon of the working fluid and by the interposition of the glass tube, the experimental results highlight the influence of the electric field on the device thermal performance and encourage the continuation of the research in this direction.

  17. Safety and Immunogenicity of a Dengue Virus Serotype-1 Purified-Inactivated Vaccine: Results of a Phase 1 Clinical Trial

    PubMed Central

    Martinez, Luis Javier; Lin, Leyi; Blaylock, Jason M.; Lyons, Arthur G.; Bauer, Kristen M.; De La Barrera, Rafael; Simmons, Monika; Jarman, Richard G.; Currier, Jeffrey R.; Friberg, Heather; Danko, Janine R.; Teneza-Mora, Nimfa C.; Putnak, J. Robert; Eckels, Kenneth H.; Thomas, Stephen J.

    2015-01-01

    We describe the results from a human clinical trial of a dengue virus serotype-1, purified-inactivated vaccine (DENV-1 PIV) adjuvanted with aluminum hydroxide. This first-in-man, Phase 1, open-label clinical trial consisted of two groups of flavivirus-naïve healthy adult volunteers that received two intramuscular vaccine doses of either 2.5 μg or 5 μg of DENV-1 PIV administered on days 0 and 28. Following vaccination, both vaccine doses exhibited an acceptable safety profile with minimal injection site and systemic reactions. By study day 42, 2 weeks following the second vaccine dose, all volunteers in both vaccine groups developed serum-neutralizing antibodies against DENV-1. Additional testing using an enzyme-linked immunosorbent assay demonstrated induction of a humoral immune response following both vaccine doses. The DENV-1 PIV was safe and immunogenic in a small number of volunteers supporting development and further testing of a tetravalent DENV PIV formulation. PMID:26149862

  18. Sensor-augmented pump therapy for A1C reduction (STAR 3) study: results from the 6-month continuation phase.

    PubMed

    Bergenstal, Richard M; Tamborlane, William V; Ahmann, Andrew; Buse, John B; Dailey, George; Davis, Stephen N; Joyce, Carol; Perkins, Bruce A; Welsh, John B; Willi, Steven M; Wood, Michael A

    2011-11-01

    OBJECTIVE To examine the effects of crossing over from optimized multiple daily injection (MDI) therapy to sensor-augmented pump (SAP) therapy for 6 months, and the effects of 18 months' sustained use of SAP. RESEARCH DESIGN AND METHODS The 6-month, single-crossover continuation phase of Sensor-Augmented Pump Therapy for A1C Reduction (STAR 3) provided SAP therapy to 420 subjects who completed the 1-year randomized study. The primary outcome was change in A1C in the crossover group. RESULTS A1C values were initially lower in the continuing-SAP group than in the crossover group (7.4 vs. 8.0%, P < 0.001). A1C values remained reduced in the SAP group. After 3 months on the SAP system, A1C decreased to 7.6% in the crossover group (P < 0.001); this was a significant and sustained decrease among both adults and children (P < 0.05). CONCLUSIONS Switching from optimized MDI to SAP therapy allowed for rapid and safe A1C reductions. Glycemic benefits of SAP therapy persist for at least 18 months.

  19. Mixed phase cloud observation in Ny-Alesund, Svalbard: Preliminary results from the May-June 2011 experiment

    NASA Astrophysics Data System (ADS)

    Shiobara, M.; Uchiyama, A.; Yamazaki, A.; Kobayashi, H.

    2011-12-01

    Clouds and aerosols are key elements having the potential to change climate by their radiative effects on the energy balance in the global climate system. In the Arctic, we have been continuing ground-based remote-sensing measurements for clouds and aerosols using a sky-radiometer, a micro-pulse lidar and an all-sky camera in Ny-Alesund (78.9N, 11.9E), Svalbard. In addition to the regular operations, we have performed an intensive observation campaign for mixed phase clouds in May-June 2011. This campaign aimed at low-level clouds to investigate cloud optical and microphysical properties and cloud-aerosol interaction processes in the Arctic, mainly from cloud radiation measurements and active remote-sensing at the surface, and in-situ microphysics measurements at the Norwegian Zeppelin Station located at a 474 meters high mountain-side. The instrumentation for in-situ measurements includes conventional cloud microphysics probes, i.e., DMT CAPS and Gerber PVM-100, and a newly developed cloud particle microscopic imager for cloud water/ice particle size distributions and the effective radius. The Rion KR-12A aerosol particle counter and the TSI 3007 condensation particle counter were placed in the ropeway cabin for measuring particle number and size distribution to see the difference between in-cloud and below-cloud conditions. We will present preliminary results from the in-situ cloud measurements for several days during the May-June 2011 field experiment.

  20. Ridaforolimus as a single agent in advanced endometrial cancer: results of a single-arm, phase 2 trial

    PubMed Central

    Colombo, N; McMeekin, D S; Schwartz, P E; Sessa, C; Gehrig, P A; Holloway, R; Braly, P; Matei, D; Morosky, A; Dodion, P F; Einstein, M H; Haluska, F

    2013-01-01

    Background: This open-label, multicentre, phase 2 trial evaluated the efficacy and tolerability of the mammalian target of rapamycin inhibitor ridaforolimus in women with advanced endometrial cancer. Methods: Women with measurable recurrent or persistent endometrial cancer and documented disease progression were treated with ridaforolimus 12.5 mg intravenously once daily for 5 consecutive days every 2 weeks in a 4-week cycle. The primary end point was clinical benefit response, defined as an objective response or prolonged stable disease of 16 weeks or more. Results: In all, 45 patients were treated with single-agent ridaforolimus. Clinical benefit was achieved by 13 patients (29%), including 5 (11%) with confirmed partial responses and 8 (18%) with prolonged stable disease. All patients with clinical benefit response received ridaforolimus for more than 4 months. In this heavily pretreated population, the 6-month progression-free survival was 18%. Ridaforolimus was generally well tolerated: adverse events were predictable and manageable, consistent with prior studies in other malignancies. Overall, the most common adverse events were diarrhoea (58%) and mouth sores (56%); most common grade 3 or higher adverse events were anaemia (27%) and hyperglycaemia (11%). Conclusion: Single-agent ridaforolimus has antitumor activity and acceptable tolerability in advanced endometrial cancer patients. Further clinical evaluation of ridaforolimus is warranted. PMID:23403817

  1. Extended Statistical Short-Range Guidance for Peak Wind Speed Analyses at the Shuttle Landing Facility: Phase II Results

    NASA Technical Reports Server (NTRS)

    Lambert, Winifred C.

    2003-01-01

    This report describes the results from Phase II of the AMU's Short-Range Statistical Forecasting task for peak winds at the Shuttle Landing Facility (SLF). The peak wind speeds are an important forecast element for the Space Shuttle and Expendable Launch Vehicle programs. The 45th Weather Squadron and the Spaceflight Meteorology Group indicate that peak winds are challenging to forecast. The Applied Meteorology Unit was tasked to develop tools that aid in short-range forecasts of peak winds at tower sites of operational interest. A seven year record of wind tower data was used in the analysis. Hourly and directional climatologies by tower and month were developed to determine the seasonal behavior of the average and peak winds. Probability density functions (PDF) of peak wind speed were calculated to determine the distribution of peak speed with average speed. These provide forecasters with a means of determining the probability of meeting or exceeding a certain peak wind given an observed or forecast average speed. A PC-based Graphical User Interface (GUI) tool was created to display the data quickly.

  2. Safety and Immunogenicity of a Dengue Virus Serotype-1 Purified-Inactivated Vaccine: Results of a Phase 1 Clinical Trial.

    PubMed

    Martinez, Luis Javier; Lin, Leyi; Blaylock, Jason M; Lyons, Arthur G; Bauer, Kristen M; De La Barrera, Rafael; Simmons, Monika; Jarman, Richard G; Currier, Jeffrey R; Friberg, Heather; Danko, Janine R; Teneza-Mora, Nimfa C; Putnak, J Robert; Eckels, Kenneth H; Thomas, Stephen J

    2015-09-01

    We describe the results from a human clinical trial of a dengue virus serotype-1, purified-inactivated vaccine (DENV-1 PIV) adjuvanted with aluminum hydroxide. This first-in-man, Phase 1, open-label clinical trial consisted of two groups of flavivirus-naïve healthy adult volunteers that received two intramuscular vaccine doses of either 2.5 μg or 5 μg of DENV-1 PIV administered on days 0 and 28. Following vaccination, both vaccine doses exhibited an acceptable safety profile with minimal injection site and systemic reactions. By study day 42, 2 weeks following the second vaccine dose, all volunteers in both vaccine groups developed serum-neutralizing antibodies against DENV-1. Additional testing using an enzyme-linked immunosorbent assay demonstrated induction of a humoral immune response following both vaccine doses. The DENV-1 PIV was safe and immunogenic in a small number of volunteers supporting development and further testing of a tetravalent DENV PIV formulation. PMID:26149862

  3. Offshore Code Comparison Collaboration within IEA Wind Task 23: Phase IV Results Regarding Floating Wind Turbine Modeling; Preprint

    SciTech Connect

    Jonkman, J.; Larsen, T.; Hansen, A.; Nygaard, T.; Maus, K.; Karimirad, M.; Gao, Z.; Moan, T.; Fylling, I.

    2010-04-01

    Offshore wind turbines are designed and analyzed using comprehensive simulation codes 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. This paper describes the latest findings of the code-to-code verification activities of the Offshore Code Comparison Collaboration, which operates under Subtask 2 of the International Energy Agency Wind Task 23. In the latest phase of the project, participants used an assortment of codes to model the coupled dynamic response of a 5-MW wind turbine installed on a floating spar buoy in 320 m of water. Code predictions were compared from load-case simulations selected to test different model features. The comparisons have resulted in a greater understanding of offshore floating wind turbine dynamics and modeling techniques, and better knowledge of the validity of various approximations. The lessons learned from this exercise have improved the participants' codes, thus improving the standard of offshore wind turbine modeling.

  4. Offshore Code Comparison Collaboration, Continuation within IEA Wind Task 30: Phase II Results Regarding a Floating Semisubmersible Wind System: Preprint

    SciTech Connect

    Robertson, A.; Jonkman, J.; Vorpahl, F.; Popko, W.; Qvist, J.; Froyd, L.; Chen, X.; Azcona, J.; Uzungoglu, E.; Guedes Soares, C.; Luan, C.; Yutong, H.; Pengcheng, F.; Yde, A.; Larsen, T.; Nichols, J.; Buils, R.; Lei, L.; Anders Nygard, T.; et al.

    2014-03-01

    Offshore wind turbines are designed and analyzed using comprehensive simulation tools (or codes) 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. This paper describes the latest findings of the code-to-code verification activities of the Offshore Code Comparison Collaboration, Continuation (OC4) project, which operates under the International Energy Agency (IEA) Wind Task 30. In the latest phase of the project, participants used an assortment of simulation codes to model the coupled dynamic response of a 5-MW wind turbine installed on a floating semisubmersible in 200 m of water. Code predictions were compared from load-case simulations selected to test different model features. The comparisons have resulted in a greater understanding of offshore floating wind turbine dynamics and modeling techniques, and better knowledge of the validity of various approximations. The lessons learned from this exercise have improved the participants? codes, thus improving the standard of offshore wind turbine modeling.

  5. Hydralazine and magnesium valproate as epigenetic treatment for myelodysplastic syndrome. Preliminary results of a phase-II trial.

    PubMed

    Candelaria, Myrna; Herrera, Aquileo; Labardini, Juan; González-Fierro, Aurora; Trejo-Becerril, Catalina; Taja-Chayeb, Lucía; Pérez-Cárdenas, Enrique; de la Cruz-Hernández, Erick; Arias-Bofill, Daymi; Vidal, Silvia; Cervera, Eduardo; Dueñas-Gonzalez, Alfonso

    2011-04-01

    Decitabine and azacitidine, two DNA methyltransferase (DNMT) inhibitors, are the current standard of treatment for myelodysplastic syndrome (MDS). Histone deacetylase (HDAC) inhibitors are also being tested against MDS. Both drug classes synergize in their gene reactivating and anticancer activities. The combination of hydralazine and valproate (Transkrip®), a DNMT and HDAC inhibitor, respectively), has been developed as epigenetic therapy under the drug repositioning concept. To evaluate the clinical efficacy and safety of hydralazine and valproate against MDS, an open phase-II study for previously treated patients with MDS was conducted. The hydralazine dose was given according with the acetylator phenotype, and valproate was dosed at 30 mg/kg/day. Response was graded with International Working Group criteria. Toxicity was evaluated by the Common Toxemia Criteria-National Cancer Institute version 3 scale. From November 2007 to January 2010, 12 patients were included. Median age±SD was 53±19.78 years (range, 23-79 years); median time from diagnosis to inclusion in the study was 7.9 months (range 2.6-36.1 months). Median of previous treatment was 2 (range, 1-6). Refractory cytopenia with multilineage dysplasia was diagnosed in ten cases, and refractory anemia with excess of blasts in two. Overall response was documented in six (50%) of 12 cases, including one CR, one PR, and four hematological improvements of the erythroid series. Two patients (16.6%) progressed to acute myeloid leukemia. Hemoglobin increased from 7.4 to 10.3 g/dL (in 13 weeks), neutrophils, from 1.1 to 2.0 (in 3 weeks), and platelets, from 66×10(9) to 72×10(9)/L (in 2 weeks). Transfusional requirements decreased from 2.3 to 0 U bi-monthly for red blood cells and from 0.5 to 0 U bi-monthly for platelets in responding patients. Main toxicities were mild, including somnolence and nausea. Preliminary results of this phase-II study suggest that the combination of hydralazine and valproate is a

  6. Design and Initial Results of a Multi-Phase Randomized Trial of Ceftriaxone in Amyotrophic Lateral Sclerosis

    PubMed Central

    Berry, James D.; Shefner, Jeremy M.; Conwit, Robin; Schoenfeld, David; Keroack, Myles; Felsenstein, Donna; Krivickas, Lisa; David, William S.; Vriesendorp, Francine; Pestronk, Alan; Caress, James B.; Katz, Jonathan; Simpson, Ericka; Rosenfeld, Jeffrey; Pascuzzi, Robert; Glass, Jonathan; Rezania, Kourosh; Rothstein, Jeffrey D.; Greenblatt, David J.; Cudkowicz, Merit E.

    2013-01-01

    Objectives Ceftriaxone increases expression of the astrocytic glutamate transporter, EAAT2, which might protect from glutamate-mediated excitotoxicity. A trial using a novel three stage nonstop design, incorporating Phases I-III, tested ceftriaxone in ALS. Stage 1 determined the cerebrospinal fluid pharmacokinetics of ceftriaxone in subjects with ALS. Stage 2 evaluated safety and tolerability for 20-weeks. Analysis of the pharmacokinetics, tolerability, and safety was used to determine the ceftriaxone dosage for Stage 3 efficacy testing. Methods In Stage 1, 66 subjects at ten clinical sites were enrolled and randomized equally into three study groups receiving intravenous placebo, ceftriaxone 2 grams daily or ceftriaxone 4 grams daily divided BID. Participants provided serum and cerebrospinal fluid for pharmacokinetic analysis on study day 7. Participants continued their assigned treatment in Stage 2. The Data and Safety Monitoring Board (DSMB) reviewed the data after the last participants completed 20 weeks on study drug. Results Stage 1 analysis revealed linear pharmacokinetics, and CSF trough levels for both dosage levels exceeding the pre-specified target trough level of 1 µM (0.55 µg/mL). Tolerability (Stages 1 and 2) results showed that ceftriaxone at dosages up to 4 grams/day was well tolerated at 20 weeks. Biliary adverse events were more common with ceftriaxone but not dose-dependent and improved with ursodeoxycholic (ursodiol) therapy. Conclusions The goals of Stages 1 and 2 of the ceftriaxone trial were successfully achieved. Based on the pre-specified decision rules, the DSMB recommended the use of ceftriaxone 4 g/d (divided BID) for Stage 3, which recently closed. Trial Registration ClinicalTrials.gov NCT00349622. PMID:23613806

  7. Cavity Attenuated Phase Shift (CAPS) Method for Airborne Aerosol Light Extinction Measurement: Instrument Validation and First Results from Field Deployment

    NASA Astrophysics Data System (ADS)

    Petzold, A.; Perim de Faria, J.; Berg, M.; Bundke, U.; Freedman, A.

    2015-12-01

    Monitoring the direct impact of aerosol particles on climate requires the continuous measurement of aerosol optical parameters like the aerosol extinction coefficient on a regular basis. Remote sensing and ground-based networks are well in place (e.g., AERONET, ACTRIS), whereas the regular in situ measurement of vertical profiles of atmospheric aerosol optical properties remains still an important challenge in quantifying climate change. The European Research Infrastructure IAGOS (In-service Aircraft for a Global Observing System; www.iagos.org) responds to the increasing requests for long-term, routine in situ observational data by using commercial passenger aircraft as measurement platform. However, scientific instrumentation for the measurement of atmospheric constituents requires major modifications before being deployable aboard in-service passenger aircraft. Recently, a compact and robust family of optical instruments based on the cavity attenuated phase shift (CAPS) technique has become available for measuring aerosol light extinction. While this technique was successfully deployed for ground-based atmospheric measurements under various conditions, its suitability for operation aboard aircraft in the free and upper free troposphere still has to be demonstrated. In this work, the modifications of a CAPS PMex instrument for measuring aerosol light extinction on aircraft, the results from subsequent laboratory tests for evaluating the modified instrument prototype, and first results from a field deployment aboard a research aircraft will be covered. In laboratory studies, the instrument showed excellent agreement (deviation < 5%) with theoretical values calculated from Rayleigh scattering cross-sections, when operated on pressurized air and CO2 at ambient and low pressure (~200 hPa). For monodisperse and polydisperse aerosols, reference aerosol extinction coefficients were calculated from measured size distributions and agreed with the CAPS PMex instrument

  8. Results from a phase 1 study of nusinersen (ISIS-SMNRx) in children with spinal muscular atrophy

    PubMed Central

    Swoboda, Kathryn J.; Darras, Basil T.; Iannaccone, Susan T.; Montes, Jacqueline; De Vivo, Darryl C.; Norris, Daniel A.; Bennett, C. Frank; Bishop, Kathie M.

    2016-01-01

    Objective: To examine safety, tolerability, pharmacokinetics, and preliminary clinical efficacy of intrathecal nusinersen (previously ISIS-SMNRx), an antisense oligonucleotide designed to alter splicing of SMN2 mRNA, in patients with childhood spinal muscular atrophy (SMA). Methods: Nusinersen was delivered by intrathecal injection to medically stable patients with type 2 and type 3 SMA aged 2–14 years in an open-label phase 1 study and its long-term extension. Four ascending single-dose levels (1, 3, 6, and 9 mg) were examined in cohorts of 6–10 participants. Participants were monitored for safety and tolerability, and CSF and plasma pharmacokinetics were measured. Exploratory efficacy endpoints included the Hammersmith Functional Motor Scale Expanded (HFMSE) and Pediatric Quality of Life Inventory. Results: A total of 28 participants enrolled in the study (n = 6 in first 3 dose cohorts; n = 10 in the 9-mg cohort). Intrathecal nusinersen was well-tolerated with no safety/tolerability concerns identified. Plasma and CSF drug levels were dose-dependent, consistent with preclinical data. Extended pharmacokinetics indicated a prolonged CSF drug half-life of 4–6 months after initial clearance. A significant increase in HFMSE scores was observed at the 9-mg dose at 3 months postdose (3.1 points; p = 0.016), which was further increased 9–14 months postdose (5.8 points; p = 0.008) during the extension study. Conclusions: Results from this study support continued development of nusinersen for treatment of SMA. Classification of evidence: This study provides Class IV evidence that in children with SMA, intrathecal nusinersen is not associated with safety or tolerability concerns. PMID:26865511

  9. Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in juvenile idiopathic arthritis: results of the phase 4 registry

    PubMed Central

    2014-01-01

    Background This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs). Methods Children aged ≥2 to <18 years with rheumatoid-factor–positive or –negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (≤6 months) an nsNSAID or celecoxib. Enrolled patients were followed to the end of the study, whether they remained on the original NSAID, switched, or discontinued therapy altogether. All adverse events (AEs) regardless of severity were captured in the database. Results A total of 274 patients (nsNSAID, n = 219; celecoxib, n = 55) were observed for 410 patient-years of observation. Naproxen, meloxicam, and nabumetone were the most frequently used nsNSAIDs. At baseline, the celecoxib group was older, had a numerically longer median time since diagnosis, and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance. AEs reported were those frequently observed with NSAID treatment and were similar across groups (nsNSAIDs: 52.0%; celecoxib: 52.9%). Twelve unique patients experienced a total of 18 serious AEs; the most frequent were infections, and none was attributed to NSAID use. Conclusions The safety profile of celecoxib and nsNSAIDs appears similar overall. The results from this registry, ongoing pharmacovigilance, and the phase 3 trial that led to the approval of celecoxib for children with JIA provide evidence that the benefit-risk for celecoxib treatment in JIA remains positive. Trial registration ClinicalTrials.gov identifier NCT00688545. PMID:25057265

  10. CONTAMINANT TRANSPORT RESULTING FROM MULTICOMPONENT NONAQUEOUS PHASE LIQUID POOL DISSOLUTION IN THREE-DIMENSIONAL SUBSURFACE FORMATIONS (R823579)

    EPA Science Inventory

    A semi-analytical method for simulating transient contaminant transport originating from the dissolution of multicomponent nonaqueous phase liquid (NAPL) pools in three-dimensional, saturated, homogeneous porous media is presented. Each dissolved component may undergo first-order...

  11. Tolerance and Acceptance Results of a Palladium-103 Permanent Breast Seed Implant Phase I/II Study

    SciTech Connect

    Pignol, Jean-Philippe Rakovitch, Eileen; Keller, Brian M.; Sankreacha, Raxa; Chartier, Carole

    2009-04-01

    Purpose: To test, in a prospective Phase I/II trial, a partial breast irradiation technique using a {sup 103}Pd permanent breast seed implant (PBSI) realized in a single 1-h procedure under sedation and local freezing. Methods and Materials: Eligible patients had infiltrating ductal carcinoma {<=}3 cm in diameter, surgical margin {>=}2 mm, no extensive intraductal component, no lymphovascular invasion, and negative lymph nodes. Patients received a permanent seed implant, and a minimal peripheral dose of 90 Gy was prescribed to the clinical target volume, with a margin of 1.5 cm. Results: From May 2004 to April 2007, 67 patients received the PBSI treatment. The procedure was well tolerated, with 17% of patients having significant pain after the procedure. Only 1 patient (1.5%) had an acute skin reaction (Grade 3 according to the National Cancer Institute Common Toxicity Criteria). The rates of acute moist desquamation, erythema, and indurations were 10.4%, 42%, and 27%, respectively. At 1 year the rate of Grade 1 telangiectasia was 14%. The rate of skin reaction decreased from 65% to 28% when skin received less than the 85% isodose. According to a Radiation Therapy Oncology Group questionnaire, 80-90% of patients were very satisfied with their treatment, and the remainder were satisfied. One patient (1.5%) developed an abscess, which resolved after the use of antibiotics. There was no recurrence after a median follow-up of 32 months (range, 11-49 months). Conclusions: The feasibility, safety, and tolerability of PBSI compares favorably with that of external beam and other partial breast irradiation techniques.

  12. Effectiveness of Cellulose Sulfate Vaginal Gel for the Prevention of HIV Infection: Results of a Phase III Trial in Nigeria

    PubMed Central

    Halpern, Vera; Ogunsola, Folasade; Obunge, Orikomaba; Wang, Chin-Hua; Onyejepu, Nneka; Oduyebo, Oyinola; Taylor, Doug; McNeil, Linda; Mehta, Neha; Umo-Otong, John; Otusanya, Sakiru; Crucitti, Tania; Abdellati, Said

    2008-01-01

    Background This trial evaluated the safety and effectiveness of 6% cellulose sulfate vaginal gel in preventing male-to-female vaginal transmission of HIV, gonorrhea and chlamydial infection. Methods This Phase III, double-blind, randomized, placebo-controlled trial was conducted between November 2004 and March 2007 in Lagos and Port Harcourt, Nigeria. We enrolled 1644 HIV-antibody negative women at high risk of HIV acquisition. Study participants were randomized 1∶1 to cellulose sulfate or placebo and asked to use gel plus a condom for each act of vaginal intercourse over one year of follow-up. The participants were evaluated monthly for HIV, gonorrhea and chlamydial infection, and for adverse events. Results The trial was stopped prematurely after the data safety monitoring board of a parallel trial concluded that cellulose sulfate might be increasing the risk of HIV. In contrast, we observed fewer infections in the active arm (10) than on placebo (13), a difference that was nonetheless not statistically significant (HR = 0.8, 95% CI 0.3–1.8; p = 0.56). Rates of gonorrhea and chlamydial infection were lower in the CS group but the difference was likewise not statistically significant (HR = 0.8, 95% CI 0.5–1.1; p = 0.19 for the combined STI outcome). Rates of adverse events were similar across study arms. No serious adverse events related to cellulose sulfate use were reported. Conclusions Cellulose sulfate gel appeared to be safe in the evaluated study population but we found insufficient evidence that it prevented male-to-female vaginal transmission of HIV, gonorrhea or chlamydial infection. The early closure of the trial compromised the ability to draw definitive conclusions about the effectiveness of cellulose sulfate against HIV. Trial Registration ClinicalTrials.gov NCT00120770 PMID:19023429

  13. NGlycolylGM3/VSSP Vaccine in Metastatic Breast Cancer Patients: Results of Phase I/IIa Clinical Trial

    PubMed Central

    de la Torre, Ana; Hernandez, Julio; Ortiz, Ramón; Cepeda, Meylán; Perez, Kirenia; Car, Adriana; Viada, Carmen; Toledo, Darién; Guerra, Pedro Pablo; García, Elena; Arboláez, Migdacelys; Fernandez, Luis E

    2012-01-01

    Patients treated with vaccines based on NGlycolil gangliosides have showed benefit in progression free survival and overall survival. These molecules, which have been observed in breast cancer cells, are minimally or not expressed in normal human tissue and have been considered as antigen tumor-specific. For this reason they are very attractive to immunotherapy. A phase I/II clinical trial was carried out in metastatic breast cancer patients with the NGlycolylGM3/VSSP vaccine administered by subcutaneous route. Selecting the optimal biological doses of the vaccine in these patients was the principal objective based on the immunogenicity, efficacy and safety results. Six levels of doses of vaccine were studied. Treatment schedule consisted of five doses every two weeks and then monthly until reaching a fifteenth doses. Doses levels studied were 150, 300, 600, 900, 1200 and 1500 μg. Five patients in each level were included except at the 900 μg dose, in which ten patients were included. Immunogenicity was determined by levels of antibodies generated in patients after vaccination. The response criteria of evaluation in solid tumors (RECIST) was used to evaluate antitumoral effect. Safety was evaluated by Common Toxicity Criteria of Adverse Event (CTCAE). The vaccine administration was safe and immunogenic in all does levels. Most frequent adverse events related to vaccination were mild or moderate and were related to injection site reactions and “flu-like” symptoms. Vaccination induced specific anti-NeuGcGM3 IgM and IgG antibodies responses in all patients. Disease control (objective response or stable disease) was obtained in 72.7% of evaluated patients. Median overall survival was 15.9 months. Two patients of two different dose levels achieved overall survival values of about six years. The dose of 900 μg was selected as biological optimal dose in which overall survival was 28.5 months. PMID:23055739

  14. Late radiation toxicity after intraoperative radiotherapy (IORT) for breast cancer: results from the randomized phase III trial TARGIT A.

    PubMed

    Sperk, Elena; Welzel, Grit; Keller, Anke; Kraus-Tiefenbacher, Uta; Gerhardt, Axel; Sütterlin, Marc; Wenz, Frederik

    2012-08-01

    The randomized phase III trial TARGIT A showed non-inferiority regarding local control after intraoperative radiotherapy (IORT 20 Gy which was followed by whole breast radiotherapy (WBRT) in patients with risk factors only) in comparison to standard WBRT (50-56 Gy) after breast-conserving surgery in selected patients. This is the first analysis of long-term toxicities in the setting of TARGIT. Between 02/2002 and 12/2008, 305 patients were treated within TARGIT A (Arm A: n = 34 IORT, n = 20 IORT + WBRT for risk factors; Arm B WBRT: n = 55) or received IORT as a planned boost (control group: n = 196) at a single center. Toxicity was assessed according to the LENT SOMA scales. No significant differences were seen between Arm A and Arm B regarding fibrosis, breast edema, retraction, ulceration, lymphedema, hyperpigmentation, and pain. Arm A had significantly less telangiectases compared to Arm B (p = 0.049). In the subanalysis (Arm A IORT vs. Arm A IORT + WBRT vs. Arm B), fibrosis had a cumulative rate of 5.9 versus 37.5 versus 18.4 %, respectively (38.2 % IORT boost control group), at 3 years. No telangiectases were seen after IORT alone (0 % Arm A IORT vs. 17.5 % Arm A IORT + WBRT vs. 17.7 % Arm B). The hazard ratio of higher grade toxicity as first event was 0.46 (95 % CI, 0.26-0.83) for Arm A IORT as compared to Arm B (p = 0.010). No recurrences were seen after a median follow-up of 40 months (Arm A) and 42 months (Arm B). With its very low chronic skin toxicity rates and outstanding long-term results regarding toxicity and local control, IORT with 50 kV X-rays is a safe and effective method for treatment of selected breast cancer patients. PMID:22842984

  15. ASB14780, an Orally Active Inhibitor of Group IVA Phospholipase A2, Is a Pharmacotherapeutic Candidate for Nonalcoholic Fatty Liver Disease.

    PubMed

    Kanai, Shiho; Ishihara, Keiichi; Kawashita, Eri; Tomoo, Toshiyuki; Nagahira, Kazuhiro; Hayashi, Yasuhiro; Akiba, Satoshi

    2016-03-01

    We have previously shown that high-fat cholesterol diet (HFCD)-induced fatty liver and carbon tetrachloride (CCl4)-induced hepatic fibrosis are reduced in mice deficient in group IVA phospholipase A2 (IVA-PLA2), which plays a role in inflammation. We herein demonstrate the beneficial effects of ASB14780 (3-[1-(4-phenoxyphenyl)-3-(2-phenylethyl)-1H-indol-5-yl]propanoic acid 2-amino-2-(hydroxymethyl)propane-1,3-diol salt), an orally active IVA-PLA2 inhibitor, on the development of fatty liver and hepatic fibrosis in mice. The daily coadministration of ASB14780 markedly ameliorated liver injury and hepatic fibrosis following 6 weeks of treatment with CCl4. ASB14780 markedly attenuated the CCl4-induced expression of smooth muscle α-actin (α-SMA) protein and the mRNA expression of collagen 1a2, α-SMA, and transforming growth factor-β1 in the liver, and inhibited the expression of monocyte/macrophage markers, CD11b and monocyte chemotactic protein-1, while preventing the recruitment of monocytes/macrophages to the liver. Importantly, ASB14780 also reduced the development of fibrosis even in matured hepatic fibrosis. Additionally, ASB14780 also reduced HFCD-induced lipid deposition not only in the liver, but also in already established fatty liver. Furthermore, treatment with ASB14780 suppressed the HFCD-induced expression of lipogenic mRNAs. The present findings suggest that an IVA-PLA2 inhibitor, such as ASB14780, could be useful for the treatment of nonalcoholic fatty liver diseases, including fatty liver and hepatic fibrosis.

  16. Effects of Additional Elements on the Evolution of Second Phases in 9-12% cr Steel and Resulting Mechanical Properties

    NASA Astrophysics Data System (ADS)

    Dong, Jiling; Yu, Hui; Yoo, Dae-Hwang; Huynh, Quocbao; Shin, Keesam; Kim, Minsoo; Kang, Sungtae

    Investigated in this study are precipitate evolution with and without addition of W, Co, and B in two kinds of 9-12% Cr steels (named as A and B) used for power plants after various aging time and temperature using OM, SEM, TEM, etc. Three kinds of precipitates (Cr-rich M23C6, Nb-rich and V-rich MX, W-rich and Mo-rich Laves phase) were observed and investigated in the two alloys. Upon aging, the area fraction of M23C6 increased whereas that of Laves phases decreased despite of increase in size. The area fraction of W-rich Laves phase was much higher than that of Mo-rich Laves phase, indicating that W addition, compared to that of Mo addition, is more powerful in the formation of Laves phase precipitation (specimen A). The martensitic microstructure of specimen B was more stable than that of specimen A due to the addition of cobalt and boron. The tensile test and impact test were measured and studied in relation to the long term aging effect.

  17. P- T phase relations of silicic, alkaline, aluminous liquids: new results and applications to mantle melting and metasomatism

    NASA Astrophysics Data System (ADS)

    Draper, David S.; Green, Trevor H.

    1999-07-01

    We report new experimental results obtained under nominally anhydrous conditions at 1.0-1.5 GPa on a synthetic melt whose composition is typical of extreme-composition xenolith glasses. These results demonstrate that part of this extreme compositional range is in equilibrium with a lherzolitic assemblage (olivine, orthopyroxene, and clinopyroxene on the liquidus), extending our earlier findings [D.S. Draper, T.H. Green P- T phase relations of silicic, alkaline, aluminous mantle-xenolith glasses under anhydrous and C-O-H fluid-saturated conditions, J. Petrol. 38 (1997) 1187-1224] showing saturation with harzburgite minerals (olivine and orthopyroxene on the liquidus). The new results strengthen the view that such liquids can readily coexist with upper mantle rocks. Our results also bear on the current debate regarding the nature of low-degree mantle melts between proponents of the diamond-aggregate technique [who argue for comparatively silica- and alkali-rich low-degree melts; e.g., M.B. Baker, M.M. Hirschmann, M.S. Ghiorso, E.M. Stolper, Compositions of near-solidus peridotite melts from experiments and thermodynamic calculations, Nature 375 (1995) 308-311; M.B. Baker, M.M. Hirschmann, L.E. Wasylenki, E.M. Stolper, M.S. Ghiorso, Quest for low-degree mantle melts, Nature 381 (1996) 286] and those favoring the sandwich technique [who question the value of the diamond-aggregate work and argue that near-solidus melts must be nepheline- and olivine-normative; T.J. Falloon, D.H. Green, H.St.C. O'Neill, C.G. Ballhaus, Quest for low-degree mantle melts, Nature 381 (1996) 285; T.J. Falloon, D.H. Green, H.St.C. O'Neill, W.O. Hibberson, Experimental tests of low degree peridotite partial melt compositions: implications for the nature of anhydrous near-solidus peridotite melts at 1 GPa, Earth Planet. Sci. Lett. 152 (1997) 149-162]. Our results support aspects of both views. The sandwich-technique view is supported, for example, because all our liquids coexisting with mantle

  18. Biodegradation kinetics of naphthalene in nonaqueous phase liquid-water mixed batch systems: Comparison of model predictions and experimental results

    SciTech Connect

    Ghoshal, S.; Luthy, R.G.

    1998-02-05

    A model is formulated to describe dissolution of naphthalene from an insoluble nonaqueous phase liquid (NAPL) and its subsequent biodegradation in the aqueous phase in completely mixed batch reactors. The physicochemical processes of equilibrium partitioning and mass transfer of naphthalene between the NAPL and aqueous phases were incorporated into the model. Biodegradation kinetics were described by Monod`s microbial growth kinetic model, modified to account for the inhibitory effects of 1,2-naphthoquinone formed during naphthalene degradation under certain conditions. System parameters and biokinetic coefficients pertinent to the NAPL-water systems were determined either by direct measurement or from nonlinear regression of the naphthalene mineralization profiles obtained from batch reactor tests with two-component NAPLs comprised of naphthalene and heptamethylnonane. The NAPLs contained substantial mass of naphthalene, and naphthalene biodegradation kinetics were evaluated over the time required for near complete depletion of naphthalene from the NAPL.

  19. Liquid/liquid metal extraction: Phase diagram topology resulting from molecular interactions between extractant, ion, oil and water

    NASA Astrophysics Data System (ADS)

    Bauer, C.; Bauduin, P.; Dufrêche, J. F.; Zemb, T.; Diat, O.

    2012-11-01

    We consider the class of surfactants called "extractants" since they specifically interact with some cations and are used in liquid-liquid separation processes. We review here features of water-poor reverse micelles in water/oil/ extractant systems as determined by combined structural studies including small angle scattering techniques on absolute scale. Origins of instabilities, liquid-liquid separation as well as emulsification failure are detected. Phase diagrams contain the same multi-phase domains as classical microemulsions, but special unusual features appear due to the high spontaneous curvature directed towards the polar cores of aggregates as well as rigidity of the film made by extracting molecules.

  20. The effect of an aqueous phase on the CO/sub 2//tetradecane and CO/sub 2//maljamar crude oil systems: Experimental and modeling results

    SciTech Connect

    Pollack, N.R.; Enick, R.M.; Holder, G.D.; Mangone, J.

    1986-01-01

    The effect of the presence of an aqueous phase on the phase behaviour of the CO/sub 2//tetradecane and the CO/sub 2//Maljamar crude oil systems has been experimentally determined. Both the salinity and the amount of the aqueous phase were varied in order to test several methods of modeling, including Henry's Law and a multiple phase equation of state method in which the brine is modeled as a single pseudo-component. The modified equation of state provided a slightly more accurate description of the observed changes in the CO/sub 2//Maljmar crude P-x diagram and was also capable of accurately predicting the aqueous phase density. Simply accounting for CO/sub 2/ solubility by incorporating Henry's Law, used in conjunction with the Poynting correction and an empirical factor for salinity, not only gave results nearly identical with the equation of state approach, but also required much less computational effort.

  1. Phase diagram of a spin-1 magnetic bilayer by cluster variational theory: Exact results for a BEG model on a Bethe lattice with five-fold coordination

    NASA Astrophysics Data System (ADS)

    Tucker, J. W.; Balcerzak, T.; Gzik, M.; Sukiennicki, A.

    1998-09-01

    The complete global phase diagram for a magnetic spin-1 bilayer, whose interactions are described by the Blume Emery Griffiths model (BEG), is studied by cluster variational theory within the pair approximation. The results obtained, are also the exact results pertaining to the BEG model on a Bethe lattice having coordination number, z=5. Useful analytic expressions are derived for trajectories in phase space containing the second-order (continuous) phase boundaries. The physical existence of these second-order boundaries, together with the location of the first-order phase boundaries, are determined from a Gibbs free energy analysis. Detailed comparison of the results with those of other workers on this, and closely related systems, is made.

  2. Involved-Node Proton Therapy in Combined Modality Therapy for Hodgkin Lymphoma: Results of a Phase 2 Study

    SciTech Connect

    Hoppe, Bradford S.; Flampouri, Stella; Zaiden, Robert; Slayton, William; Sandler, Eric; Dang, Nam H.; Lynch, James W.; Li, Zuofeng; Morris, Christopher G.; Mendenhall, Nancy P.

    2014-08-01

    Purpose: This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. Methods and Materials: Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on {sup 18}F-Fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. Results: The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. Conclusions: Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes

  3. Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia: Results From an International, Phase III Clinical Trial.

    PubMed

    Kane, John M; Zukin, Stephen; Wang, Yao; Lu, Kaifeng; Ruth, Adam; Nagy, Krisztián; Laszlovszky, István; Durgam, Suresh

    2015-08-01

    This phase III study evaluated the efficacy and safety of cariprazine, a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, in patients with acute exacerbation of schizophrenia. Patients were randomized to 6-week double-blind treatment with placebo, cariprazine 3 to 6 mg/d, or cariprazine 6 to 9 mg/d. Primary and secondary efficacy: change from baseline to week 6 in Positive and Negative Syndrome Scale total and Clinical Global Impressions-Severity scores, respectively, analyzed using a mixed-effects model for repeated measures adjusting for multiple comparisons. Safety included treatment-emergent adverse events, clinical laboratory values, vital signs, electrocardiograms, ophthalmologic examination, Columbia-Suicide Severity Rating Scale, and extrapyramidal symptom scales. In the Safety Population (placebo, n = 147; cariprazine 3-6 mg/d, n = 151; cariprazine 6-9 mg/d, n = 148), 60.5% of patients completed the study. At week 6, statistically significant least squares mean differences in favor of cariprazine versus placebo were observed for Positive and Negative Syndrome Scale total score (3-6 mg/d: -6.8, P = 0.003; 6-9 mg/d: -9.9, P < 0.001) and Clinical Global Impressions-Severity (3-6 mg/d: -0.3, P = 0.012; 6-9 mg/d: -0.5, P < 0.001). Common treatment-emergent adverse events (≥5% and twice the rate of placebo) in both cariprazine groups were akathisia, extrapyramidal disorder, and tremor; most were mild to moderate in severity. Mean changes in metabolic parameters were generally small and similar between groups. Prolactin levels decreased in all groups. In conclusion, cariprazine 3 to 6 and 6 to 9 mg/d versus placebo demonstrated significant improvement on primary and secondary efficacy parameters. Cariprazine was generally well tolerated. These results suggest that cariprazine may be a new and effective treatment for schizophrenia. PMID:26075487

  4. An observational approach for determining aerosol surface radiative forcing: Results from the first field phase of INDOEX

    NASA Astrophysics Data System (ADS)

    Conant, William C.

    2000-06-01

    This paper presents one of the few quantitative estimates of surface aerosol forcing made directly from surface irradiance observations. The method described within yields estimates of the forcing accurate to 20%. The study was conducted from February to March 1998 at the Kaashidhoo Climate Observatory (KCO) during the First Field Phase of the Indian Ocean Experiment (INDOEX-FFP). For the 400-700 nm region studied here, the forcing is -7.6±1.5 W m-2. The data are obtained from two photodiode radiometers measuring global and diffuse irradiance in five channels in the visible and ultraviolet. The instruments were chosen, calibrated, and deployed specifically for a precise measurement of aerosol forcing. The angular, spectral, and absolute response characteristics of the instruments are determined in the laboratory and used to calibrate the data, as described here. The accuracy in the calibrated data is 2.4% for the global irradiance and 1.8% for the diffuse irradiance. Direct aerosol forcing is obtained from the measured aerosol forcing efficiency, which is determined by two methods: hybrid and differential. The hybrid method uses a radiative transfer model to subtract out the contribution from the aerosol-free atmosphere. The differential method assumes that changes in 400-700 nm solar flux are forced by changes in aerosol optical depth. By using flux changes, the differential method is not sensitive to the small calibration uncertainties, and is independent of model assumptions about the single-scatter properties of the aerosol. For this soot-laden marine region south of India, a 0.1 change in aerosol optical depth produces a -4.0±0.8 W m-2; change in the 400-700 nm surface flux; 55% of this forcing is observed in the 400-540 nm region. The global and diffuse data agree to within 5 W m-2 of results calculated by a Monte Carlo radiative transfer model. The model assumes an aerosol consistent with the spectral optical depth, lidar vertical profiles, and surface

  5. Intensive-Phase Treatment Outcomes among Hospitalized Multidrug-Resistant Tuberculosis Patients: Results from a Nationwide Cohort in Nigeria

    PubMed Central

    Oladimeji, Olanrewaju; Isaakidis, Petros; Obasanya, Olusegun J.; Eltayeb, Osman; Khogali, Mohammed; Van den Bergh, Rafael; Kumar, Ajay M. V.; Hinderaker, Sven Gudmund; Abdurrahman, Saddiq T.; Lawson, Lovett; Cuevas, Luis E.

    2014-01-01

    Background Nigeria is faced with a high burden of Human Immunodeficiency Virus (HIV) infection and multidrug-resistant tuberculosis (MDR-TB). Treatment outcomes among MDR-TB patients registered across the globe have been poor, partly due to high loss-to-follow-up. To address this challenge, MDR-TB patients in Nigeria are hospitalized during the intensive-phase(IP) of treatment (first 6–8 months) and are provided with a package of care including standardized MDR-TB treatment regimen, antiretroviral therapy (ART) and cotrimoxazole prophylaxis (CPT) for HIV-infected patients, nutritional and psychosocial support. In this study, we report the end-IP treatment outcomes among them. Methods In this retrospective cohort study, we reviewed the patient records of all bacteriologically-confirmed MDR-TB patients admitted for treatment between July 2010 and October 2012. Results Of 162 patients, 105(65%) were male, median age was 34 years and 28(17%) were HIV-infected; all 28 received ART and CPT. Overall, 138(85%) were alive and culture negative at the end of IP, 24(15%) died and there was no loss-to-follow-up. Mortality was related to low CD4-counts at baseline among HIV-positive patients. The median increase in body mass index among those documented to be underweight was 2.6 kg/m2 (p<0.01) and CD4-counts improved by a median of 52 cells/microL among the HIV-infected patients (p<0.01). Conclusions End-IP treatment outcomes were exceptional compared to previously published data from international cohorts, thus confirming the usefulness of a hospitalized model of care. However, less than five percent of all estimated 3600 MDR-TB patients in Nigeria were initiated on treatment during the study period. Given the expected scale-up of MDR-TB care, the hospitalized model is challenging to sustain and the national TB programme is contemplating to move to ambulatory care. Hence, we recommend using both ambulatory and hospitalized approaches, with the latter being reserved for

  6. Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006)

    PubMed Central

    Hjorth-Hansen, Henrik; Stenke, Leif; Söderlund, Stina; Dreimane, Arta; Ehrencrona, Hans; Gedde-Dahl, Tobias; Gjertsen, Bjørn Tore; Höglund, Martin; Koskenvesa, Perttu; Lotfi, Kourosh; Majeed, Waleed; Markevärn, Berit; Ohm, Lotta; Olsson-Strömberg, Ulla; Remes, Kari; Suominen, Merja; Simonsson, Bengt; Porkka, Kimmo; Mustjoki, Satu; Richter, Johan

    2015-01-01

    We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100 mg QD or imatinib 400 mg QD and report outcome as an intention-to-treat analysis with 36 months follow-up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR3.0 was reached at 3 months in 36% vs. 8% (P = 0.02), at 12 months in 81% vs. 46% (P = 0.02) and at 18 months in 73% vs. 65% (n.s.) of the patients in the two groups. In contrast, MR4.5 was consistently superior in the dasatinib group at all time points from 6 months onwards, reaching 61% vs. 21% (P < 0.05) at 36 months. Sixty-four vs. 71% of the patients in the dasatinib and imatinib arms, respectively, remained on assigned drug. Dasatinib dose was frequently reduced, but with maintained excellent effect. One imatinib patient progressed to blastic phase, but no CML-related deaths occurred. In conclusion, our data compare favourably with those of the dasatinib registration study, DASISION. The fast and deep molecular responses induced by dasatinib compared with imatinib may be exploited to increase the proportion of patients who can achieve a treatment-free remission after treatment discontinuation. PMID:25082346

  7. [Socio-political aspects of toxoplasmosis epidemic in Santa Isabel do Ivaí, Paraná State, Brazil].

    PubMed

    de Almeida, Márcio José; de Oliveira, Luzia Helena Herrmann; Freire, Roberta Lemos; Navarro, Italmar Teodorico

    2011-01-01

    In 2002, due to a toxoplasmosis epidemic Santa Isabel do Ivaí, Paraná State, was the focus of sanitary investigations. Four hundred and twenty six individuals had serology suggestive of acute T. gondii infection (IgM reactor), considered the largest outbreak of toxoplasmosis ever reported in the world. This research was meant to identify actions carried out by the sanitation and health services sector at that time, highlighting the political conflicts that took place during the process and identifying the measures taken by the sanitary authorities during and after the epidemic period. This is an interdisciplinary study aimed at understanding major problems of public health like this one. The investigation was based on the contents of documents--press and institutional--and interviews. According to official data, the epidemic was caused by the contamination of one of the water reservoirs that supply the city. This research showed that political and social factors, as the party instability and the level of political dependence of local society, were largely responsible for the occurrence of the epidemic and for the difficulties faced by the health agents during such crisis.

  8. Evaluation of Flygt Mixers for Application in Savannah River Site Tank 19 Test Results from Phase B: Mid-Scale Testing at PNNL

    SciTech Connect

    Powell, M.R.; Combs, W.H.; Farmer, J.R.; Gladki, H.; Hatchell, B.K.; Johnson, M.A.; Poirier, M.R.; Rodwell, P.O.

    1999-03-30

    Pacific Northwest National Laboratory (PNNL) performed mixer tests using 3-kW (4-hp) Flygt mixers in 1.8- and 5.7-m-diameter tanks at the 336 building facility in Richland, Washington to evaluate candidate scaling relationships for Flygt mixers used for sludge mobilization and particle suspension. These tests constituted the second phase of a three-phase test program involving representatives from ITT Flygt Corporation, the Savannah River Site (SRS), the Oak Ridge National Laboratory (ORNL), and PNNL. The results of the first phase of tests, which were conducted at ITT Flygt's facility in a 0.45-m-diameter tank, are documented in Powell et al. (1999). Although some of the Phase B tests were geometrically similar to selected Phase A tests (0.45-m tank), none of the Phase B tests were geometrically, cinematically, and/or dynamically similar to the planned Tank 19 mixing system. Therefore, the mixing observed during the Phase B tests is not directly indicative of the mixing expected in Tank 19 and some extrapolation of the data is required to make predictions for Tank 19 mixing. Of particular concern is the size of the mixer propellers used for the 5.7-m tank tests. These propellers were more than three times larger than required by geometric scaling of the Tank 19 mixers. The implications of the lack of geometric similarity, as well as other factors that complicate interpretation of the test results, are discussed in Section 5.4.

  9. An investigation of wing buffeting response at subsonic and transonic speeds. Phase 2: F-111A flight data analysis. Volume 1: Summary of technical approach, results and conclusions

    NASA Technical Reports Server (NTRS)

    Benepe, D. B.; Cunningham, A. M., Jr.; Traylor, S., Jr.; Dunmyer, W. D.

    1978-01-01

    A detailed investigation of the flight buffeting response of the F-111A was performed in two phases. In Phase 1 stochastic analysis techniques were applied to wing and fuselage responses for maneuvers flown at subsonic speeds and wing leading edge sweep of 26 degrees. Power spectra and rms values were obtained. This report gives results of Phase 2 where the analyses were extended to include maneuvers flown at wing leading edge sweep values of 50 and 75.5 degrees at subsonic and supersonic speeds and the responses examined were expanded to include vertical shear, bending moment, and hingeline torque of the left and right horizontal tails. Power spectra, response time histories, variations of rms response with angle of attack and effects of wing sweep and Mach number are presented and discussed. Some Phase 1 results are given for comparison purposes.

  10. Initial test results from the RedFlow 5 kW, 10 kWh zinc-bromide module, phase 1.

    SciTech Connect

    Ferreira, Summer Rhodes; Rose, David Martin

    2012-02-01

    In this paper the performance results of the RedFlow zinc-bromide module (ZBM) Gen 2.0 are reported for Phase 1 of testing, which includes initial characterization of the module. This included physical measurement, efficiency as a function of charge and discharge rates, efficiency as a function of maximum charge capacity, duration of maximum power supplied, and limited cycling with skipped strip cycles. The goal of this first phase of testing was to verify manufacturer specifications of the zinc-bromide flow battery. Initial characterization tests have shown that the ZBM meets the manufacturer's specifications. Further testing, including testing as a function of temperature and life cycle testing, will be carried out during Phase 2 of the testing, and these results will be issued in the final report, after Phase 2 testing has concluded.

  11. The IAEA coordinated research programme on HTGR uncertainty analysis: Phase I status and Ex. I-1 prismatic reference results

    DOE PAGES

    Bostelmann, Friederike; Strydom, Gerhard; Reitsma, Frederik; Ivanov, Kostadin

    2016-01-11

    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, in contrast to the historical approach where sensitivity analysis were performed and uncertainties then determined by a simplified statistical combination of a few important inputmore » parameters. New methodologies are currently under development in the OECD/NEA Light Water Reactor (LWR) Uncertainty Analysis in Best-Estimate Modelling (UAM) benchmark activity. High Temperature Gas-cooled Reactor (HTGR) designs require specific treatment of the double heterogeneous fuel design and large graphite quantities at high temperatures. The IAEA has therefore launched a Coordinated Research Project (CRP) on HTGR Uncertainty Analysis in Modelling (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 Chinese HTR-PM. Work has started on the first phase and the current CRP status is reported in the paper. A comparison of the Serpent and SCALE/KENO-VI reference Monte Carlo results for Ex. I-1 of the MHTGR-350 design is also included. It was observed that the SCALE/KENO-VI Continuous Energy (CE) k∞ values were 395 pcm (Ex. I-1a) to 803 pcm (Ex. I-1b) higher than the respective Serpent lattice calculations, and that within the set of the SCALE results, the KENO-VI 238 Multi-Group (MG) k∞ values were up to 800 pcm lower than the KENO-VI CE values. The use of the

  12. Feed system design and experimental results in the uhf model study for the proposed Urbana phased array

    NASA Technical Reports Server (NTRS)

    Loane, J. T.; Bowhill, S. A.; Mayes, P. E.

    1982-01-01

    The effects of atmospheric turbulence and the basis for the coherent scatter radar techniques are discussed. The reasons are given for upgrading the Radar system to a larger steerable array. Phase array theory pertinent to the system design is reviewed, along with approximations for maximum directive gain and blind angles due to mutual coupling. The methods and construction techniques employed in the UHF model study are explained. The antenna range is described, with a block diagram for the mode of operation used.

  13. Phase compensation of MARSIS subsurface sounding data and estimation of ionospheric properties: New insights from SHARAD results

    NASA Astrophysics Data System (ADS)

    Campbell, Bruce A.; Watters, Thomas R.

    2016-02-01

    Subsurface radar sounding observations by the Mars Advanced Radar for Subsurface and Ionospheric Sounding (MARSIS) and Shallow Radar (SHARAD) instruments are affected by ionospheric phase distortions that lead to image blurring and delay offsets. Based on experience with SHARAD image correction, we propose that ionospheric blurring in MARSIS radargrams may be compensated with a model of smoothly varying quadratic phase errors along the track. This method yields well-focused radargrams for geologic interpretation and allows analysis of the validity range for models used to derive total electron content (TEC) from phase distortion terms in previous MARSIS studies. The quadratic term appears to be a good proxy for TEC at solar zenith angles >65° for MARSIS Band 4 (5 MHz) and >75° for Band 3 (4 MHz). Comparison of MARSIS- and SHARAD-derived TEC values from 2007 to 2014 reveals correlations in seasonal behavior and in the characterization of ionospheric activity due to coronal mass ejections. We also present SHARAD and MARSIS evidence for a persistent region of anomalous radar scattering south of Arsia Mons. These echoes have been previously suggested to arise from refraction of the radar signal by electron density variations. There are no strong signatures, however, in the quadratic image compensation term correlated with the anomalous scattering, suggesting either that electron density variations responsible for refracted signal paths occur primarily in regions offset from the spacecraft track or that these density changes have a minimal impact on the integrated phase distortion of the subspacecraft footprint. We suggest observations and analyses to better constrain the mechanism and timing of such echoes.

  14. Results from One- and Two- Phase Fluid Flow Calculations within the Preliminary Safety Analysis of the Gorleben Site - 13310

    SciTech Connect

    Kock, Ingo; Larue, Juergen; Fischer, Heidi; Frieling, Gerd; Navarro, Martin; Seher, Holger

    2013-07-01

    Rock salt is one of the possible host rock formations for the disposal of high-level radioactive wastes in Germany. The Preliminary Safety Analysis of the Gorleben Site (Vorlaeufige Sicherheitsanalyse Gorleben, VSG) evaluates the long-term safety of a hypothetical repository in the salt dome of Gorleben, Germany. A mature repository concept and detailed knowledge of the site allowed a detailed process analysis within the project by numerical modeling of single-phase and two-phase flow. The possibility of liquid transport from the shafts to the emplacement drifts is one objective of the present study. Also, the implications of brine inflow on radionuclide transport and gas generation are investigated. Pressure build-up due to rock convergence and gas generation, release of volatile radionuclides from the waste and pressure-driven contaminant transport were considered, too. The study confirms that the compaction behavior of salt grit backfill is one of the most relevant factors for the hydrodynamic evolution of the repository and the transport of contaminants. Due to the interaction between compaction, saturation and pore pressure, complex flow patterns evolve. Emplacement drifts serve as gas sinks or sources at different times. In most calculation cases, the backfill reaches its final porosity after a few hundred years. The repository is then sealed and radionuclides can only be transported by diffusion in the liquid phase. Estimates for the final porosity of compacted backfill range between 0 % and 2 %. The exact properties of the backfill regarding single- and two-phase flow are not well known for this porosity range. The study highlights that this uncertainty has a profound impact on flow and transport processes over long time-scales. Therefore, more research is needed to characterize the properties of crushed salt grit at low porosities or to reduce the adverse effects of possible higher porosities by repository optimization. (authors)

  15. HIGH LEVEL WASTE (HLW) SLUDGE BATCH 4 (SB4) WITH FRIT 418: RESULTS OF A PHASE II VARIABILITY STUDY

    SciTech Connect

    Fox, K; Tommy Edwards, T; David Peeler, D; David Best, D; Irene Reamer, I; Phyllis Workman, P

    2007-01-29

    In early October 2006, the Liquid Waste Organization (LWO) began to consider decanting Tank 40 at the end of Sludge Batch 3 (SB3) processing and transferring the aqueous phase from the decant to Tank 51. This transfer would be done to remove water added to Tank 40 by a slurry pump bearing water leak. Tank 40 decant water would be used to decrease Tank 51 yield stress and facilitate a transfer of Tank 51 to Tank 40. The projected composition of Sludge Batch 4 (SB4) was adjusted by LWO to reflect the impact of the Tank 40 decant leading to new projected compositions for SB4, designated as the 10-04-06 and the 10-10-06 compositions. A comparison between these SB4 compositions and those provided in June 2006 indicated that the new compositions are slightly higher in Al2O3, Fe2O3, and U3O8 and slightly lower in SiO2. The most dramatic change, however, is the new projection's Na2O concentration, which is more than 4.5 wt% lower than the June 2006 projection. This is a significant change due to the frit development team's approach of aligning the Na2O concentration in a candidate frit to the Na2O content of the sludge. Questions surfaced regarding the applicability of Frit 503 to these revised compositions since the Savannah River National Laboratory (SRNL) recommended Frit 503 for use with SB4 based on the June 2006 compositional projection without the Tank 40 decant. Based on paper study assessments, the change in SB4's expected Na2O content had a significant, negative impact on the projected operating window for the Frit 503/SB4 glass system. Frit 418 had a slightly larger operating window for the 10-04-06 projection (as compared to a lower Na2O frit, Frit 503) and the Frit 418/10-04-06 glass system was no longer nepheline limited. Thus, strictly from the perspective of this paper study, Frit 418 was more attractive than Frit 503 for the new SB4 projected compositions. This comparison, however, did not reflect other aspects of interest for the glass systems such as

  16. Chikusetsu Saponin IVa Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice via Adiponectin-Mediated AMPK/GSK-3β Pathway In Vivo and In Vitro.

    PubMed

    Duan, Jialin; Yin, Ying; Cui, Jia; Yan, Jiajia; Zhu, Yanrong; Guan, Yue; Wei, Guo; Weng, Yan; Wu, Xiaoxiao; Guo, Chao; Wang, Yanhua; Xi, Miaomiao; Wen, Aidong

    2016-01-01

    Diabetes mellitus substantially increases the risk of stroke and enhances brain's vulnerability to ischemia insult. In a previous study, Chikusetsu saponin IVa (CHS) pretreatment was proved to protect the brain from cerebral ischemic in normal stroke models. Whether CHS could attenuate cerebral ischemia/reperfusion (I/R) injury in diabetic mice and the possible underlying mechanism are still unrevealed. Male C57BL/6 mice were injected streptozotocin to induce diabetes. After that, the mice were pretreated with CHS for 1 month, and then, focal cerebral ischemia was induced following 24-h reperfusion. The neurobehavioral scores, infarction volumes, and some cytokines in the brain were measured. Apoptosis was analyzed by caspase-3, Bax, and Bcl-2 expression. Downstream molecules of adiponectin (APN) were investigated by Western blotting. The results showed that CHS reduced infarct size, improved neurological outcomes, and inhibited cell injury after I/R. In addition, CHS pretreatment increased APN level and enhanced neuronal AdipoR1, adenosine monophosphate-activated protein kinase (AMPK), and glycogen synthase kinase 3 beta (GSK-3β) expression in a concentration-dependent manner in diabetic mice, and these effects were abolished by APN knockout (KO). In vitro test, CHS treatment also alleviated PC12 cell injury and apoptosis, evidenced by reduced tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA) and caspase-3 expression, and Bax/Bcl-2 ratio in I/R injured cells. Moreover, CHS enhanced AdipoR1, AMPK, and GSK-3β expression in a concentration-dependent manner. Likewise, short interfering RNA (sinRNA) knockdown of liver kinase B1 (LKB1), an upstream kinase of AMPK, reduced the ability of CHS in protecting cells from I/R injury. Furthermore, this LKB1-dependent cellular protection resulted from AdipoR1 and APN activation, as supported by the experiment using sinRNA knockdown of AdipoR1 and APN. Thus, CHS protected brain I/R in diabetes through AMPK

  17. New results from the analyses of the solid phase of the NASA Ames Titan Haze Simulation (THS) experiment

    NASA Astrophysics Data System (ADS)

    Sciamma-O'Brien, Ella; Upton, Kathleen T.; Beauchamp, Jesse L.; Salama, Farid

    2015-11-01

    In Titan’s atmosphere, a complex chemistry occurs at low temperature between N2 and CH4 that leads to the production of heavy organic molecules and subsequently solid aerosols. The Titan Haze Simulation (THS) experiment was developed at the NASA Ames COSmIC facility to study Titan’s atmospheric chemistry at low temperature. In the THS, the chemistry is simulated by plasma in the stream of a supersonic expansion. With this unique design, the gas is cooled to Titan-like temperature (~150K) before inducing the chemistry by plasma, and remains at low temperature in the plasma (~200K). Different N2-CH4-based gas mixtures can be injected in the plasma, with or without the addition of heavier molecules, in order to monitor the evolution of the chemical growth.Following a recent in situ mass spectrometry study of the gas phase that demonstrated that the THS is a unique tool to probe the first and intermediate steps of Titan’s atmospheric chemistry at low temperature (Sciamma-O’Brien et al., Icarus, 243, 325 (2014)), we have performed a complementary study of the solid phase. The findings are consistent with the chemical growth evolution observed in the gas phase. Grains and aggregates form in the gas phase and can be jet deposited onto various substrates for ex situ analyses. Scanning Electron Microscopy images show that more complex mixtures produce larger aggregates, and that different growth mechanisms seem to occur depending on the gas mixture. They also allow the determination of the size distribution of the THS solid grains. A Direct Analysis in Real Time mass spectrometry analysis coupled with Collision Induced Dissociation has detected the presence of aminoacetonitrile, a precursor of glycine, in the THS aerosols. X-ray Absorption Near Edge Structure (XANES) measurements also show the presence of imine and nitrile functional groups, showing evidence of nitrogen chemistry. Infrared and µIR spectra of samples deposited on KBr and Si substrates show the

  18. Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study.

    PubMed

    Diamond, Michael P; Carr, Bruce; Dmowski, W Paul; Koltun, William; O'Brien, Chris; Jiang, Ping; Burke, Joshua; Jimenez, Roland; Garner, Elizabeth; Chwalisz, Kristof

    2014-03-01

    This Phase 2 study evaluated the safety and efficacy of elagolix for treating endometriosis-associated pain. A total of 155 women with laparoscopically confirmed endometriosis were randomized to placebo, elagolix 150 mg, or elagolix 250 mg once daily for 12 weeks. Placebo patients were rerandomized to elagolix and elagolix patients continued their dosing assignment for 12 additional weeks; the primary efficacy measure was changed from baseline in the monthly mean numerical rating scale for pain at week 12. Monthly mean (standard error of the mean) reductions were greater with elagolix versus placebo (-1.19 ± 0.18, -1.25 ± 0.18, and -0.88 ± 0.18 for elagolix 150 mg, 250 mg, and placebo, respectively); differences were not statistically significant. Monthly mean dysmenorrhea and nonmenstrual pelvic pain scores were reduced with elagolix, with significant differences for dysmenorrhea at weeks 8 and 12 versus placebo (P < .05). Minimal bone mineral density changes were observed with elagolix treatment. In women with endometriosis-associated pain, elagolix demonstrated an acceptable efficacy and safety profile in this Phase 2 study.

  19. An extracellular quinoprotein oxidase that catalyzes conversion of enacyloxin IVa to enacyloxin IIa.

    PubMed

    Oyama, R; Watanabe, T; Hanzawa, H; Sano, T; Sugiyama, T; Izaki, K

    1994-10-01

    A new extracellular quinoprotein oxidase named enacyloxin oxidase (ENX oxidase), which is involved in biosynthesis of ENX IIa, a congener of ENX, was found in the culture supernatant of Frateuria sp. W-315 and purified as a homogeneous protein on SDS-PAGE. ENX oxidase was shown to have a molecular mass of 73 kDa by SDS-PAGE and 79 kDa by gel filtration. The enzyme was inhibited by various carbonyl reagents and the activity was stimulated by addition of PQQ. This is the first report on a quinoprotein oxidase that is secreted into the culture medium in the logarithmic growth phase, and acts for biosynthesis of the antibiotic.

  20. Study of the suit inflation effect on crew safety during landing using a full-pressure IVA suit for new-generation reentry space vehicles

    NASA Astrophysics Data System (ADS)

    Wataru, Suzuki

    Recently, manned space capsules have been recognized as beneficial and reasonable human space vehicles again. The Dragon capsule already achieved several significant successes. The Orion capsule is going to be sent to a high-apogee orbit without crews for experimental purposes in September 2014. For such human-rated space capsules, the study of acceleration impacts against the human body during splashdown is essential to ensure the safety of crews. Moreover, it is also known that wearing a full pressure rescue suit significantly increases safety of a crew, compared to wearing a partial pressure suit. This is mainly because it enables the use of a personal life support system independently in addition to that which installed in the space vehicle. However, it is unclear how the inflation of the full pressure suit due to pressurization affects the crew safety during splashdown, especially in the case of the new generation manned space vehicles. Therefore, the purpose of this work is to investigate the effect of the suit inflation on crew safety against acceleration impact during splashdown. For this objective, the displacements of the safety harness in relation with the suit, a human surrogate, and the crew seats during pressurizing the suit in order to determine if the safety and survivability of a crew can be improved by wearing a full pressure suit. For these tests, the DL/H-1 full pressure IVA suit, developed by Pablo de Leon and Gary L. Harris, will be used. These tests use image analysis techniques to determine the displacements. It is expected, as a result of these tests, that wearing a full pressure suit will help to mitigate the impacts and will increase the safety and survivability of a crew during landing since it works as a buffer to mitigate impact forces during splashdown. This work also proposes a future plan for sled test experiments using a sled facility such as the one in use by the Civil Aerospace Medical Institute (CAMI) for experimental validation

  1. Results of Phase 1 postburn drilling and coring, Rocky Mountain 1 Underground Coal Gasification Site, Hanna Basin, Wyoming

    SciTech Connect

    Lindblom, S.R.; Covell, J.R.; Oliver, R.L.

    1990-09-01

    The Rocky Mountain 1 (RM1) Underground Coal Gasification (UCG) test consisted of two different module configurations: the controlled retracting injection point (CRIP) and elongated linked well (ELW) configurations. The postburn coring of the RM1 UCG site was designed in two phases to fulfill seven objectives outlined in the Western Research Institute's (WRI) annual project plan for 1988--1989. The seven objectives were to (1) delineate the areal extent of the cavities, (2) identify the extent of roof collapse, (3) obtain samples of all major cavity rock types, (4) characterize outflow channels and cavity stratigraphy, (5) characterize the area near CRIP points and ignition points, (6) further define the structural geology of the site, and (7) identify the vertical positioning of the horizontal process wells within the coal seam. Phase 1 of the coring was completed in the summer of 1989 and served to partially accomplish all seven objectives. In relation to the seven objectives, WRI determined that (1) the ELW cavity extends farther to the west and the CRIP cavity was located 5--10 feet farther to the south than anticipated; (2) roof collapse was contained within unit A in both modules; (3) samples of all major rock types were recovered; (4) insufficient data were obtained to characterize the outflow channels, but cavity stratigraphy was well defined; (5) bore holes near the CRIP points and ignition point did not exhibit characteristics significantly different from other bore holes in the cavities; (6) a fault zone was detected between VIW=1 and VIW-2 that stepped down to the east; and (7) PW-1 was only 7--12 feet below the top of the coal seam in the eastern part of the ELW module area; and CIW-1 was located 18--20 feet below the top of the coal seam in the CRIP module area. 7 refs., 7 figs., 1 tab.

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

    NASA Astrophysics Data System (ADS)

    Kong, Fang; Li, Pei-Xin; Zhang, Su-Yun; Mao, Jiang-Gao

    2012-06-01

    Systematic explorations of new phases in the GaIII/InIII/GeIV-SeIV-O systems by hydrothermal syntheses or solid-state reactions at high-temperature led to six new ternary compounds, namely, M2Se2O7 (M=Ga 1, In 2), M(OH)(SeO3) (M=Ga 3, In 4), α-Ge(SeO3)25 and β-Ge(SeO3)26. Ga2Se2O71 displays a 3D open framework composed of 2D gallium oxide layers being further bridged and capped by SeO3 groups. In2Se2O72 features a 3D indium oxide framework formed by corner- and edge- sharing InO6 octahedra with SeO3 groups attached on the cavities and the 8-member ring tunnels of the structure. The isostructural of M(OH)(SeO3) (M=Ga 3, In 4) exhibit a 2D metal selenite layer composed of 1D edge-sharing MO6 octahedral chains that are interconnected by SeO3 groups. α-Ge(SeO3)2 (P21/n) 5 displays a 3D open framework with 1D 8-member ring tunnels along the a-axis while β-Ge(SeO3)2 (Pa-3) 6 exhibits a condensed 3D network.

  3. High-solids black liquor firing in pulp and paper industry kraft recovery boilers: Phase 1 -- Final report. Volume 2: Project technical results

    SciTech Connect

    Southards, W.T.; Clement, J.L.; McIlroy, R.A.; Tharp, M.R.; Verrill, C.L.; Wessell, R.A.

    1995-11-01

    This project is a multiple-phase effort to develop technologies to improve high-solids black liquor firing in pulp mill recovery boilers. The principal means to this end is to construct and operate a pilot-scale recovery furnace simulator (RFS) in which these technologies can be tested. The Phase 1 objectives are to prepare a preliminary design for the RFS, delineate a project concept for evaluating candidate technologies, establish industrial partners, and report the results. Phase 1 addressed the objectives with seven tasks: Develop a preliminary design of the RFS; estimate the detailed design and construction costs of the RFS and the balance of the project; identify interested parties in the paper industry and key suppliers; plan the Phase 2 and Phase 3 tests to characterize the RFS; evaluate the economic justification for high-solids firing deployment in the industry; evaluate high-solids black liquor property data to support the RFS design; manage the project and reporting results, which included planning the future program direction.

  4. High intensity focused ultrasound (HIFU) treatment of BPH: results of a multi-center phase III study

    NASA Astrophysics Data System (ADS)

    Sanghvi, N.; Gardner, T.; Koch, M.; Bihrle, R.; Foster, R.; Resnick, M.; Seftel, A.; Grunberger, I.; Stiedle, C.; Corchan, J.

    2003-04-01

    The five centers phase III trial was to show that HIFU can treat prostate tissue thermally for symptomatic relief of BPH and improve flow rates. At five sites, 68 BPH patients were treated with the Sonablate device (Focus Surgery, Inc. Indianapolis, IN). A urethral Foley catheter was inserted into the urethra to aid in positioning and was kept in-situ during the treatment. A cooling device was used to cool the rectal wall. The patients returned home within a few hours after the procedure. The Foley catheter was kept electively to avoid any incidence of acute urinary retention following the therapy. The catheter was removed after 4-5 days. The average treatment time was 38 minutes. The patients were treated without pain, blood loss or complications. At 90 days post treatment, average Qmax and AUA Symptom Scores improved from 8.7 ml/s to 12.66 ml/s (48%) and 23.06 to 11.62 (52%), respectively. Significant prostate tissue changes took place before and after the treatment. 80% of the patients had cavity formation at the site of treatment at the bladder neck and prostate. Nonsurgical HIFU therapy is safe and effective for providing symptomatic relief of BPH symptoms and the treatment can be performed as an outpatient procedure.

  5. Deferasirox in patients with iron overload secondary to hereditary hemochromatosis: results of a 1-yr Phase 2 study.

    PubMed

    Cançado, Rodolfo; Melo, Murilo R; de Moraes Bastos, Roberto; Santos, Paulo C J L; Guerra-Shinohara, Elivira M; Chiattone, Carlos; Ballas, Samir K

    2015-12-01

    This open-label, prospective, phase 2 study evaluated the safety and efficacy of deferasirox (10 ± 5 mg/kg/d) in patients with hereditary hemochromatosis (HH) and iron overload refractory to or intolerant of phlebotomy. Ten patients were enrolled and all completed the 12-month treatment period. There were significant decreases from baseline to end of study (i.e., 12 months) in median serum ferritin (P < 0.001), mean transferrin saturation (P < 0.05), median liver iron concentration (P < 0.001), and mean alanine aminotransferase (P < 0.05). The median time to achieve serum ferritin reduction ≥50% compared to baseline was 7.53 months. The most common adverse events were mild, transient diarrhea (n = 5) and nausea (n = 2). No patient experienced an increase in serum creatinine that exceeded the upper limit of normal. These data confirm that deferasirox was well tolerated and effective in reducing iron burden in patients with hereditary hemochromatosis and could be a safe alternative to phlebotomy in selected patients.

  6. Far infrared spectra of amorphous and crystalline water ice and changes in these phases as the result of proton irradiation

    NASA Technical Reports Server (NTRS)

    Hudson, Reggie L.; Moore, Marla H.

    1992-01-01

    Far infrared spectra from 20 microns (500 cm(sup -1)) to 100 microns (100 cm(sup -1)) of water ice were measured. Amorphous ice deposited at 13 K has one absorption band at 45 microns (220 cm(sup -1)). Amorphous ice evolves into a crystalline form with absorptions at 44 microns (229 cm(sup -1)) and 62 microns (162 cm(sup -1)) as the temperature is increased to 155 K. Spectra documenting this phase change are presented as well as spectra of crystalline ice at temperatures between 13 K and 155 K. Far infrared spectra of amorphous and crystalline water ice before and after proton irradiation are also presented. Changes in these two forms are discussed in relation to ices in comets, grains, and planetary satellites in various radiation environments. Observations of non-terrestrial clathrate hydrates are still lacking despite the fact that clathrates first were suggested to exist in cometary and interstellar ices over forty years ago. Spectroscopy, the most direct method of astronomical detection, has been hampered by the similarity of clathrate hydrate spectra to those of unenclathrated guest molecules and solid H2O. A methanol (CH3OH) clathrate hydrate, using a recently published procedure, was prepared and its far-IR spectrum investigated. The spectrum is quite differenct from that of either unenclathrated CH3OH or solid H2O and so should be of value in astronomical searches for this clathrate.

  7. Results of Phase I of the Development of Course Content and Teaching Guides for a Total Curriculum in Concrete Technology. Interim Report.

    ERIC Educational Resources Information Center

    Piper, James D.; And Others

    In this first phase, job descriptions and need for trained concrete technologists within the concrete-using industries were determined by survey. The project staff created curriculum materials which were reviewed by outside authorities and put into workable lesson plans by a group of educational consultants. The result was a six-volume set of…

  8. Results of a Randomized Phase I Gene Therapy Clinical Trial of Nononcolytic Fowlpox Viruses Encoding T Cell Costimulatory Molecules

    PubMed Central

    Kim, Dae Won; Kim-Schulze, Seunghee; DeRaffele, Gail; Jagoda, Michael C.; Broucek, Joseph R.; Zloza, Andrew

    2014-01-01

    Abstract Oncolytic viruses have shown promise as gene delivery vehicles in the treatment of cancer; however, their efficacy may be inhibited by the induction of anti-viral antibody titers. Fowlpox virus is a nonreplicating and nononcolytic vector that has been associated with lesser humoral but greater cell-mediated immunity in animal tumor models. To test whether fowlpox virus gene therapy is safe and can elicit immune responses in patients with cancer, we conducted a randomized phase I clinical trial of two recombinant fowlpox viruses encoding human B7.1 or a triad of costimulatory molecules (B7.1, ICAM-1, and LFA-3; TRICOM). Twelve patients (10 with melanoma and 2 with colon adenocarcinoma) enrolled in the trial and were randomized to rF-B7.1 or rF-TRICOM administered in a dose escalation manner (∼3.7×107 or ∼3.7×108 plaque-forming units) by intralesional injection every 4 weeks. The therapy was well tolerated, with only four patients experiencing grade 1 fever or injection site pain, and there were no serious adverse events. All patients developed anti-viral antibody titers after vector delivery, and posttreatment anti-carcinoembryonic antigen antibody titers were detected in the two patients with colon cancer. All patients developed CD8+ T cell responses against fowlpox virus, but few responses against defined tumor-associated antigens were observed. This is the first clinical trial of direct (intratumoral) gene therapy with a nononcolytic fowlpox virus. Treatment was well tolerated in patients with metastatic cancer; all subjects exhibited anti-viral antibody responses, but limited tumor-specific T cell responses were detected. Nononcolytic fowlpox viruses are safe and induce limited T cell responses in patients with cancer. Further development may include prime–boost strategies using oncolytic viruses for initial priming. PMID:24484178

  9. Neoadjuvant capecitabine, bevacizumab and radiotherapy for locally advanced rectal cancer: results of a single-institute Phase I study.

    PubMed

    Miki, Yoshitaka; Maeda, Kiyoshi; Hosono, Masako; Nagahara, Hisashi; Hirakawa, Kosei; Shimatani, Yasuhiko; Tsutsumi, Shinichi; Miki, Yukio

    2014-11-01

    The aim of this Phase I clinical trial was to assess the feasibility and safety of capecitabine-based preoperative chemoradiotherapy (CRT) combined with bevacizumab and to determine the optimal capecitabine dose for Japanese patients with locally advanced rectal cancer. Patients with cT3/T4 rectal cancer were eligible. Bevacizumab was administered at 5 mg/kg intravenously on Days 1, 15 and 29. Capecitabine was administered on weekdays concurrently with pelvic radiotherapy at a daily dose of 1.8 Gy, totally to 50.4 Gy. Capecitabine was initiated at 825 mg/m(2) twice daily at Dose Level 1, with a planned escalation to 900 mg/m(2) twice daily at Dose Level 2. Within 6.1-10.3 (median, 9.4) weeks after the completion of the CRT, surgery was performed. Three patients were enrolled at each dose level. Regarding the CRT-related acute toxicities, all of the adverse events were limited to Grade 1. There was no Grade 2 or greater toxicity. No patient needed attenuation or interruption of bevacizumab, capecitabine or radiation. All of the patients received the scheduled dose of CRT. All of the patients underwent R0 resection. Two (33.3%) of the six patients had a pathological complete response, and five (83.3%) patients experienced downstaging. In total, three patients (50%) developed postoperative complications. One patient developed an intrapelvic abscess and healed with incisional drainage. The other two patients healed following conservative treatment. This regimen was safely performed as preoperative CRT for Japanese patients with locally advanced rectal cancer. The recommended capecitabine dose is 900 mg/m(2) twice daily.

  10. Three-dimensional mixed-wet random pore-scale network modeling of two- and three-phase flow in porous media. II. Results.

    PubMed

    Piri, Mohammad; Blunt, Martin J

    2005-02-01

    We use the model described in Piri and Blunt [Phys. Rev. E 71, 026301 (2005)] to predict two- and three-phase relative permeabilities of Berea sandstone using a random network to represent the pore space. We predict measured relative permeabilities for two-phase flow in a water-wet system. We then successfully predict the steady-state oil, water, and gas three-phase relative permeabilities measured by Oak (Proceedings of the SPE/DOE Seventh Symposium on Enhanced Oil Recovery, Tulsa, OK, 1990). We also study secondary and tertiary gas injection into media of different wettability and initial oil saturation and interpret the results in terms of pore-scale displacement processes.

  11. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study

    PubMed Central

    Bible, Keith C; Suman, Vera J; Molina, Julian R; Smallridge, Robert C; Maples, William J; Menefee, Michael E; Rubin, Joseph; Sideras, Kostandinos; Morris, John C; McIver, Bryan; Burton, Jill K; Webster, Kevin P; Bieber, Carolyn; Traynor, Anne M; Flynn, Patrick J; Goh, Boon Cher; Tang, Hui; Ivy, Susan Percy; Erlichman, Charles

    2011-01-01

    Summary Background Chemotherapy has historically proven ineffective in advanced differentiated thyroid cancers, but the realisation that various tyrosine kinases are activated in the disease suggested a potential therapeutic role for tyrosine-kinase inhibitors. We investigated the safety and efficacy of pazopanib. Methods This phase 2 trial was done from Feb 22, 2008, to Jan 31, 2009, in patients with metastatic, rapidly progressive, radioiodine-refractory differentiated thyroid cancers. Each patient received 800 mg continuous pazopanib daily in 4-week cycles until disease progression, drug intolerance, or both occurred. Up to two previous therapies were allowed, and measurable disease with radiographic progression in the 6-month period before enrolment was a requirement for inclusion. The primary endpoint was any tumour response, according to the Response Evaluation Criteria in Solid Tumors 1.0. This study is registered with ClinicalTrials.gov, number NCT00625846. Findings 39 patients were enrolled. One patient had received no previous radioiodine therapy and another withdrew consent before treatment. Clinical outcomes could, therefore, be assessed in 37 patients (19 [51%] men, median age 63 years). The study is closed to accrual of new patients, but several enrolled patients are still being treated. Patients received a median of 12 cycles (range 1 to >23, total >383). Confirmed partial responses were recorded in 18 patients (response rate 49%, 95% CI 35–68), with likelihood of response lasting longer than 1 year calculated to be 66%. Maximum concentration of pazopanib in plasma during cycle one was significantly correlated with radiographic response (r=−0·40, p=0·021). 16 (43%) patients required dose reductions owing to adverse events, the most frequent of which (any grade) were fatigue (29 patients), skin and hair hypopigmentation (28), diarrhoea (27), and nausea (27). Two patients who died during treatment had pre-existing contributory disorders

  12. Study for identification of beneficial uses of space, phase 1. Volume 2, book 1: Technical report, introduction, methodology, results

    NASA Technical Reports Server (NTRS)

    1973-01-01

    A study was conducted to determine the beneficial uses of space and to identify the products, processes, or services that will be best developed or produced in the unique environment offered by spacecraft. The subjects discussed are: (1) review of study background, (2) specific users and uses, (3) methodology, and (4) basic data generated and significant results.

  13. Isotopic evolution of Mauna Kea volcano: Results from the initial phase of the Hawaii Scientific Drilling Project

    USGS Publications Warehouse

    Lassiter, J.C.; DePaolo, D.J.; Tatsumoto, M.

    1996-01-01

    We have examined the Sr, Nd, and Pb isotopic compositions of Mauna Kea lavas recovered by the first drilling phase of the Hawaii Scientific Drilling Project. These lavas, which range in age from ???200 to 400 ka, provide a detailed record of chemical and isotopic changes in basalt composition during the shied/postshield transition and extend our record of Mauna Kea volcanism to a late-shield period roughly equivalent to the last ???100 ka of Mauna Loa activity. Stratigraphic variations in isotopic composition reveal a gradual shift over time toward a more depleted source composition (e.g., higher 143Nd/144Nd, lower 87Sr/86Sr, and lower 3He/4He). This gradual evolution is in sharp contrast with the abrupt appearance of alkalic lavas at ???240 ka recorded by the upper 50 m of Mauna Kea lavas from the core. Intercalated tholeiitic and alkalic lavas from the uppermost Mauna Kea section are isotopically indistinguishable. Combined with major element evidence (e.g., decreasing SiO2 and increasing FeO) that the depth of melt segregation increased during the transition from tholeiitic to alkalic volcanism, the isotopic similarity of tholeiitic and alkalic lavas argues against significant lithosphere involvement during melt generation. Instead, the depleted isotopic signatures found in late shield-stage lavas are best explained by increasing the proportion of melt generated from a depleted upper mantle component entrained and heated by the rising central plume. Direct comparison of Mauna Kea and Mauna Loa lavas erupted at equivalent stages in these volcanoes' life cycles reveals persistent chemical and isotopic differences independent of the temporal evolution of each volcano. The oldest lavas recovered from the drillcore are similar to modern Kilauea lavas, but are distinct from Mauna Loa lavas. Mauna Kea lavas have higher 143Nd/144Nd and 206Pb/204Pb and lower 87Sr/86Sr. Higher concentrations of incompatible trace elements in primary magmas, lower SiO2, and higher FeO also

  14. Comparison of phase velocities from array measurements of Rayleigh waves associated with microtremor and results calculated from borehole shear-wave velocity profiles

    USGS Publications Warehouse

    Liu, Hsi-Ping; Boore, David M.; Joyner, William B.; Oppenheimer, David H.; Warrick, Richard E.; Zhang, Wenbo; Hamilton, John C.; Brown, Leo T.

    2000-01-01

    Shear-wave velocities (VS) are widely used for earthquake ground-motion site characterization. VS data are now largely obtained using borehole methods. Drilling holes, however, is expensive. Nonintrusive surface methods are inexpensive for obtaining VS information, but not many comparisons with direct borehole measurements have been published. Because different assumptions are used in data interpretation of each surface method and public safety is involved in site characterization for engineering structures, it is important to validate the surface methods by additional comparisons with borehole measurements. We compare results obtained from a particular surface method (array measurement of surface waves associated with microtremor) with results obtained from borehole methods. Using a 10-element nested-triangular array of 100-m aperture, we measured surface-wave phase velocities at two California sites, Garner Valley near Hemet and Hollister Municipal Airport. The Garner Valley site is located at an ancient lake bed where water-saturated sediment overlies decomposed granite on top of granite bedrock. Our array was deployed at a location where seismic velocities had been determined to a depth of 500 m by borehole methods. At Hollister, where the near-surface sediment consists of clay, sand, and gravel, we determined phase velocities using an array located close to a 60-m deep borehole where downhole velocity logs already exist. Because we want to assess the measurements uncomplicated by uncertainties introduced by the inversion process, we compare our phase-velocity results with the borehole VS depth profile by calculating fundamental-mode Rayleigh-wave phase velocities from an earth model constructed from the borehole data. For wavelengths less than ~2 times of the array aperture at Garner Valley, phase-velocity results from array measurements agree with the calculated Rayleigh-wave velocities to better than 11%. Measurement errors become larger for wavelengths 2

  15. Water- and Air-Quality Monitoring of Sweetwater Reservoir Watershed, San Diego County, California - Phase One Results Continued, 2001-2003

    USGS Publications Warehouse

    Mendez, Gregory O.; Foreman, William T.; Morita, Andrew; Majewski, Michael S.

    2008-01-01

    In 1998, the U.S. Geological Survey, in cooperation with the Sweetwater Authority, began a study to monitor water, air, and sediment at the Sweetwater and Loveland Reservoirs in San Diego County, California. The study includes regular sampling of water and air at Sweetwater Reservoir for chemical constituents, including volatile organic compounds (VOC), polynuclear aromatic hydrocarbons (PAH), pesticides, and major and trace elements. The purpose of this study is to monitor changes in contaminant composition and concentration during the construction and operation of State Route 125. To accomplish this, the study was divided into two phases. Phase One sampling (water years 1998-2004) determined baseline conditions for the detection frequency and the concentrations of target compounds in air and water. Phase Two sampling (starting water year 2005) continues at selected monitoring sites during and after construction of State Route 125 to assess the chemical impact this roadway alignment may have on water quality in the reservoir. Water samples were collected for VOCs and pesticides at Loveland Reservoir during Phase One and will be collected during Phase Two for comparison purposes. Air samples collected to monitor changes in VOCs, PAHs, and pesticides were analyzed by adapting methods used to analyze water samples. Bed-sediment samples have been and will be collected three times during the study; at the beginning of Phase One, at the start of Phase Two, and near the end of the study. In addition to the ongoing data collection, several special studies were initiated to assess the occurrence of specific chemicals of concern, such as trace metals, anthropogenic indicator compounds, and pharmaceuticals. This report describes the study design, and the sampling and analytical methods, and presents data from water and air samples collected during the fourth and fifth years of Phase One of the study (October 2001 to September 2003). Data collected during the first three

  16. Modeling of Developing Inhomogeneities in the Ferrite Microstructure and Resulting Mechanical Properties Induced by Deformation in the Two-Phase Region

    SciTech Connect

    Majta, J; Zurek, A.K.; Pietrzyk, M.

    1999-07-13

    The differences in microstructure development of hot deformed steels in the austenite and two-phase region have been effectively described using an integrated computer modeling process. In general, the complete model presented here takes into account kinetics of recrystallization, precipitation, phase transformation, recrystallized austenite grain size, ferrite grain size, and the resulting mechanical properties. The transformation submodel of niobium-microalloyed steels is based on the nucleation and grain growth theory and additivity rule. The thermomechanical part of the modeling process was effectively carried out using the finite element method. Results were obtained in different temperatures, strain rates, and range of deformation. The thermomechanical treatments are different for two grades of niobium-steels to make possible analysis of the resulting structure and properties for different histories of deformation and chemical composition.

  17. Ca(2+) -complex stability of GAPAGPLIVPY peptide in gas and aqueous phase, investigated by affinity capillary electrophoresis and molecular dynamics simulations and compared to mass spectrometric results.

    PubMed

    Nachbar, Markus; El Deeb, Sami; Mozafari, Mona; Alhazmi, Hassan A; Preu, Lutz; Redweik, Sabine; Lehmann, Wolf Dieter; Wätzig, Hermann

    2016-03-01

    Strong, sequence-specific gas-phase bindings between proline-rich peptides and alkaline earth metal ions in nanoESI-MS experiments were reported by Lehmann et al. (Rapid Commun. Mass Spectrom. 2006, 20, 2404-2410), however its relevance for physiological-like aqueous phase is uncertain. Therefore, the complexes should also be studied in aqueous solution and the relevance of the MS method for binding studies be evaluated. A mobility shift ACE method was used for determining the binding between the small peptide GAPAGPLIVPY and various metal ions in aqueous solution. The findings were compared to the MS results and further explained using computational methods. While the MS data showed a strong alkaline earth ion binding, the ACE results showed nonsignificant binding. The proposed vacuum state complex also decomposed during a molecular dynamic simulation in aqueous solution. This study shows that the formed stable peptide-metal ion adducts in the gas phase by ESI-MS does not imply the existence of analogous adducts in the aqueous phase. Comparing peptide-metal ion interaction under the gaseous MS and aqueous ACE conditions showed huge difference in binding behavior.

  18. Raising the bar for enthusiasm when looking at results of randomized phase II trials-the case of sunitinib in small-cell lung cancer.

    PubMed

    Di Maio, Massimo; Bironzo, Paolo; Scagliotti, Giorgio Vittorio

    2016-02-01

    With the advent of targeted agents, randomized phase II trials designed with explicit comparative intent, to allow a better interpretation of the results obtained with experimental treatment, have become a common approach for anti-cancer drug development. In the Cancer and Leukemia Group B (CALGB) 30504 randomized phase II trial, patients with extensive-stage small-cell lung cancer (SCLC), without progression after four to six cycles of standard chemotherapy with cisplatin or carboplatin plus etoposide, were randomized to sunitinib or placebo, until disease progression. Primary endpoint of the study was progression-free survival (PFS), and the results were formally positive [hazard ratio (HR) 0.62; one-sided P=0.02]. However, the prognosis of patients with extensive-stage SCLC is particularly bad, and even a relevant relative benefit (i.e., an encouraging HR) will likely correspond to a debatable absolute benefit: the difference in median PFS between patients treated with sunitinib and patients assigned to control arm was slightly higher than 1.5 months. Is this difference in median PFS big enough to predict a clinically relevant benefit in overall survival? Unfortunately, we do not know. From a "clinical" point of view, is this small absolute improvement in PFS relevant enough to further invest in the strategy? Probably not, also considering the absence of known predictive factors. If the results of the phase II trial had been really promising, the subsequent phase III study should have been promptly conducted, but this was not the case. It seems that, this time, the bar for enthusiasm was already raised in the phase II setting.

  19. Clinical Results of an Automated Artificial Pancreas Using Technosphere Inhaled Insulin to Mimic First-Phase Insulin Secretion

    PubMed Central

    Zisser, Howard; Dassau, Eyal; Lee, Justin J.; Harvey, Rebecca A.; Bevier, Wendy; Doyle, Francis J.

    2015-01-01

    Objective: The purpose of this study was to investigate whether or not adding a fixed preprandial dose of inhaled insulin to a fully automated closed loop artificial pancreas would improve the postprandial glucose control without adding an increased risk of hypoglycemia. Research Design and Methods: Nine subjects with T1DM were recruited for the study. The patients were on closed-loop control for 24 hours starting around 4:30 pm. Mixed meals (~50 g CHO) were given at 6:30 pm and 7:00 am the following day. For the treatment group each meal was preceded by the inhalation of one 10 U dose of Technosphere Insulin (TI). Subcutaneous insulin delivery was controlled by a zone model predictive control algorithm (zone-MPC). At 11:00 am, the patient exercised for 30 ± 5 minutes at 50% of predicted heart rate reserve. Results: The use of TI resulted in increasing the median percentage time in range (70-180 mg/dl, BG) during the 5-hour postprandial period by 21.6% (81.6% and 60% in the with/without TI cases, respectively, P = .06) and reducing the median postprandial glucose peak by 33 mg/dl (172 mg/dl and 205 mg/dl in the with and without TI cases, respectively, P = .004). The median percentage time in range 80-140 mg/dl during the entire study period was 67.5% as compared to percentage time in range without the use of TI of 55.2% (P = .03). Conclusions: Adding preprandial TI (See video supplement) to an automated closed-loop AP system resulted in superior postprandial control as demonstrated by lower postprandial glucose exposure without addition hypoglycemia. PMID:25901023

  20. Systemic Inhibition of Canonical Notch Signaling Results in Sustained Callus Inflammation and Alters Multiple Phases of Fracture Healing

    PubMed Central

    Dishowitz, Michael I.; Mutyaba, Patricia L.; Takacs, Joel D.; Barr, Andrew M.; Engiles, Julie B.; Ahn, Jaimo; Hankenson, Kurt D.

    2013-01-01

    The Notch signaling pathway is an important regulator of embryological bone development, and many aspects of development are recapitulated during bone repair. We have previously reported that Notch signaling components are upregulated during bone fracture healing. However, the significance of the Notch pathway in bone regeneration has not been described. Therefore, the objective of this study was to determine the importance of Notch signaling in regulating bone fracture healing by using a temporally controlled inducible transgenic mouse model (Mx1-Cre;dnMAMLf/-) to impair RBPjκ-mediated canonical Notch signaling. The Mx1 promoter was synthetically activated resulting in temporally regulated systemic dnMAML expression just prior to creation of bilateral tibial fractures. This allowed for mice to undergo unaltered embryological and post-natal skeletal development. Results showed that systemic Notch inhibition prolonged expression of inflammatory cytokines and neutrophil cell inflammation, and reduced the proportion of cartilage formation within the callus at 10 days-post-fracture (dpf) Notch inhibition did not affect early bone formation at 10dpf, but significantly altered bone maturation and remodeling at 20dpf. Increased bone volume fraction in dnMAML fractures, which was due to a moderate decrease in callus size with no change in bone mass, coincided with increased trabecular thickness but decreased connectivity density, indicating that patterning of bone was altered. Notch inhibition decreased total osteogenic cell density, which was comprised of more osteocytes rather than osteoblasts. dnMAML also decreased osteoclast density, suggesting that osteoclast activity may also be important for altered fracture healing. It is likely that systemic Notch inhibition had both direct effects within cell types as well as indirect effects initiated by temporally upstream events in the fracture healing cascade. Surprisingly, Notch inhibition did not alter cell proliferation

  1. Crack-arrest tests on two irradiated high-copper welds. Phase 2: Results of duplex-type experiments

    SciTech Connect

    Iskander, S.K.; Corwin, W.R.; Nanstad, R.K.

    1994-03-01

    The objective of the Heavy-Section Steel Irradiation Program Sixth Irradiation Series is to determine the effect of neutron irradiation on the shift and shape of the lower-bound curve to crack-arrest toughness data. Two submerged-arc welds with copper contents of 0.23 and 0.31 wt % were commercially fabricated in 220-mm-thick plate. Crack-arrest specimens fabricated from these welds were irradiated at a nominal temperature of 288{degrees}C to an average fluence of 1.9 {times} 10{sup 19} neutrons/cm{sup 2} (>1 MeV). This is the second report giving the results of the tests on irradiated duplex-type crack-arrest specimens. A previous report gave results of tests on irradiated weld-embrittled-type specimens. Charpy V-notch (CVN) specimens irradiated in the same capsules as the crack-arrest specimens were also tested, and a 41-J transition temperature shift was determined from these specimens. {open_quotes}Mean{close_quote} curves of the same form as the American Society of Mechanical Engineers (ASME) K{sub la} curve were fit to the data with only the {open_quotes}reference temperature{close_quotes} as a parameter. The shift between the mean curves agrees well with the 41-J transition temperature shift obtained from the CVN specimen tests. Moreover, the four data points resulting from tests on the duplex crack-arrest specimens of the present study did not make a significant change to mean curve fits to either the previously obtained data or all the data combined.

  2. Results of research to develop cost effective biomonitoring at oil shale lease tracts. Phase I. Fall sampling report

    SciTech Connect

    Skalski, J.R.; Fitzner, R.E.; Gano, K.A.

    1982-05-01

    This report presents the results of censuses conducted during October 1981 to estimate the fall abundance of small mammals and avifauna on replicate plots in the vicinity of Federal Tract C-a (Rio Blanco Oil Shale Company). The objectives of the fall censuses were to evaluate alternative census techniques, test assumptions vital to the use of indices and abundance estimators, determine cost-functions associated with monitoring efforts, and estimate variance components needed to devise optimal monitoring designs. Analyses of the fall census data on small mammal abundance were performed.

  3. Phase III Integrated Water Recovery Testing at MSFC - Closed hygiene and potable loop test results and lesson learned

    NASA Technical Reports Server (NTRS)

    Holder, Donald W., Jr.; Bagdigian, Robert M.

    1992-01-01

    A series of tests has been conducted at the NASA Marshall Space Flight Center (MSFC) to evaluate the performance of a Space Station Freedom (SSF) pre-development water recovery system. Potable, hygiene, and urine reclamation subsystems were integrated with end-use equipment items and successfully operated for a total of 35 days, including 23 days in closed-loop mode with man-in-the-loop. Although several significant subsystem physical anomalies were encountered, reclaimed potable and hygiene water routinely met current SSF water quality specifications. This paper summarizes the test objectives, system design, test activities/protocols, significant results/anomalies, and major lessons learned.

  4. Allozyme comparison of two populations of Rineloricaria (Siluriformes, Loricariidae) from the Ivaí River, upper Paraná River basin, Brazil

    PubMed Central

    2009-01-01

    Two allopatric morphotypes of the genus Rinelocaria were compared through the allozyme electrophoresis technique: one morphotype, R. pentamaculata, from the Keller River in the middle stretch of the Ivaí River basin and the other, R. aff. pentamaculata, from the São João River in the upper portion of the Ivaí River basin. The morphotype from the São João River was collected upstream from the São João waterfall, which is about 80 m deep. Twelve enzymatic systems (AAT, ADH, EST, GCDH, G3PDH, GPI, IDH, LDH, MDH, ME, PGM and SOD) were analyzed, which allowed to score 22 loci. Only lociAat-2, Est-3 and Mdh-C showed polymorphism. The two samples differed in allele frequencies at the three polymorphic loci. The average expected heterozygosity for all loci was 0.0806 ± 0.0447 in the Keller River sample. For the São João River morphotype, this value was 0.0489 ± 0.0350. Nei' s genetic identity and distance between the two populations were respectively 0.9789 and 0.0213. Wright's FIS , FIT and FST over all loci were estimated as 0.3121, 0.4021 and 0.1309, respectively. We consider that the two morphotypes represent species in statunascendi. PMID:21637702

  5. Design and code validation of the Jupiter inductive voltage adder (IVA) PRS driver

    SciTech Connect

    Mazarakis, M.G.; Poukey, J.W.; Mendel, C.W.

    1995-07-01

    The proposed Jupiter accelerator is a {approximately} 10-MV, 500-TW system capable of delivering 15-MJ kinetic energy to an imploding plasma radiation source (PRS). The accelerator is based on Hermes-III technology and contains 30 identical inductive voltage adder modules connected in parallel. The modules drive a common circular convolute electrode system in the center of which is located an imploding foil. The relatively high voltage of 8--10 MV is required to compensate for the voltage differential generated across the load due primarily to the fast increase in current (L di/dt) and to lesser extent to the increasing inductance(I dL/dt) and resistive component of the imploding foil. Here we examine the power flow through the device and, in particular, through the voltage adder and long MITL. Analytical models, such as pressure balance and parapotential flow, as well as circuit and PIC codes, were utilized. A new version of the TWOQUICK PIC code, which includes an imploding, cylindrical foil as load, was utilized to compare the power flow calculations done with SCREAMER and TRIFL. The agreement is very satisfactory and adds confidence to the Jupiter design. In addition, an experimental validation of the design is under way this year (FY95) with Hermes III. Long extension MITLs are connected at the end of the voltage adder with inductive and diode loads to benchmark the above design codes. In this paper we outline the accelerator`s conceptual design with emphasis on the power flow and coupling to the inductive load and include preliminary results of Hermes-III experimental design validation.

  6. Phase III integrated water recovery testing at MSFC - Partially closed hygiene loop and open potable loop results and lessons learned

    NASA Technical Reports Server (NTRS)

    Bagdigian, R. M.; Traweek, M. S.; Griffith, G. K.; Griffin, M. R.

    1991-01-01

    A series of tests has been conducted at the NASA Marshall Space Flight Center (MSFC) to evaluate the performance of a predevelopment water recovery system. Potable, hygiene, and urine reclamation subsystems were integrated with end-use equipment items and successfully operated in open and partially closed-loop modes, with man-in-the-loop, for a total of 28 days. Several significant subsystem physical anomalies were encountered during testing. Reclaimed potable and hygiene water generally met the current Space Station Freedom (SSF) water quality specifications for inorganic and microbiological constituents, but exceeded the maximum allowable concentrations for Total Organic Carbon (TOC). This paper summarizes the test objectives, system design, test activities/protocols, significant results/anomalies, and major lessons learned.

  7. Results of a phase I/II clinical trial: standardized, non-xenogenic, cultivated limbal stem cell transplantation

    PubMed Central

    2014-01-01

    Background To determine if a standardized, non-xenogenic, reduced manipulation cultivation and surgical transplantation of limbal stem cell grafts is a safe and effective treatment option for patients with total and partial limbal stem cell deficiency. Methods In vitro cellular outgrowth and phenotype of the limbal epithelial cell and composite grafts were validated using a new protocol. Patients received either autologous (n = 15) or allogenic (n = 3) explants cultured using a standardized protocol free from xenogenic products. The resulting grafts were transplanted using a reduced manipulation surgical technique. Results The majority of cells (>50%) displayed a progenitor phenotype typified by positive immunofluorescence for ∆Np63, CK14 and ABCG2 and low immunofluorescence for CK3/12 and desmoglein 3 proteins. The surgical protocol was designed to minimize manipulation and the graft itself was secured without sutures. The transplant recipients were followed for a mean of 24 months. Twelve of the 18 transplant recipients were graded as anatomically successful (67%), based on the defined success parameters. There was a significant reduction in corneal neovascularization, which was accompanied by an improvement in pain though not photophobia or central corneal opacity post transplant. The transplantation protocol showed no measureable effect on visual acuity. Conclusion We conclude that this standardized culture system and surgical approach is safe and effective in reducing corneal neovascularization. The technique is free from animal contaminants and maintains a large proportion of progenitor cells. Although this technique did not improve visual function, restoring a functional epithelial cell layer and reducing corneal neovascularization provides an improved platform for a penetrating keratoplasty to ultimately improve visual function. PMID:24589151

  8. Preliminary results of a phase I/II study of simultaneous modulated accelerated radiotherapy for nondisseminated nasopharyngeal carcinoma

    SciTech Connect

    Lee, Sang-wook . E-mail: lsw@amc.seoul.kr; Back, Geum Mun; Yi, Byong Yong; Choi, Eun Kyung; Ahn, Seung Do; Shin, Seong Soo; Kim, Jung-hun; Kim, Sang Yoon; Lee, Bong-Jae; Nam, Soon Yuhl; Choi, Seung-Ho; Kim, Seung-Bae; Park, Jin-hong; Lee, Kang Kyoo; Park, Sung Ho; Kim, Jong Hoon

    2006-05-01

    Purpose: To present preliminary results of intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). Methods and Materials: Twenty patients who underwent IMRT for nondisseminated NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. Intensity-modulated radiotherapy was delivered with the 'step and shoot' SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume, 60 Gy (2 Gy/day) to the clinical target volume and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received cisplatin once per week. Results: The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had Radiation Therapy Oncology Group Grade 3 mucositis, whereas 9 (45%) had Grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no Grade 3 or 4 xerostomia. All patients showed complete response. Two patients had distant metastases and locoregional recurrence, respectively. Conclusion: Intensity-modulated radiotherapy with the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and might also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.

  9. Ciliary Neurotrophic Factor (CNTF) for Macular Telangiectasia Type 2 (MacTel): Results from a phase I safety trial

    PubMed Central

    Chew, Emily Y.; Clemons, Traci E.; Peto, Tunde; Sallo, Ferenc B.; Ingerman, Avner; Tao, Weng; Singerman, Lawrence; Schwartz, Steven D.; Peachey, Neal S.; Bird, Alan C.

    2015-01-01

    PURPOSE To evaluate the safety and tolerability of intraocular delivery of ciliary neurotrophic factor (CNTF) using an encapsulated cell implant for the treatment of macular telangiectasia type 2. DESIGN An open-labeled safety trial conducted in 2 centers enrolling 7 participants with macular telangiectasia type 2. METHODS The participant’s more severely affected eye (worse baseline visual acuity) received the high dose implant of CNTF. Patients were followed for a period of 36 months. The primary safety outcome was a change in the parameters of the electroretinogram (ERG). Secondary efficacy outcomes were changes in visual acuity, en face measurements of the optical coherence tomography of the disruption in the ellipsoid zone, and microperimetry when compared with baseline. RESULTS The ERG findings demonstrated a reduction in the amplitude of the scotopic b-wave in 4 participants 3 months after implantation (month 3). All parameters returned to baseline values by month 12 and remained so at month 36 with no clinical impact on dark adaptation. There was no change in visual acuity compared with baseline. The area of the defect as measured functionally by microperimetry and structurally by the en face OCT imaging of the ellipsoid zone loss appeared unchanged from baseline. CONCLUSIONS The intraocular delivery of CNTF in the encapsulated cell implant appeared to be safe and well tolerated in eyes with macular telangiectasia type 2. Further evaluation in a randomized controlled clinical trial is warranted to test for efficacy. PMID:25528956

  10. Wind estimates from cloud motions: Preliminary results from phases 1, 2, and 3 of an in situ aircraft verification experiment

    NASA Technical Reports Server (NTRS)

    Hasler, A. F.; Shenk, W. E.; Skillman, W. C.

    1975-01-01

    Low level aircraft equipped with Inertial Navigation Systems (INS) were used to define the vertical extent and horizontal motion of a cloud and to measure the ambient wind field. A high level aircraft, also equipped with an INS, took photographs to describe the horizontal extent of the cloud field and to measure cloud motion. The aerial photographs were also used to make a positive identification in a satellite picture of the cloud observed by the low level aircraft. The experiment was conducted over the tropical oceans in the vicinity of Florida, Puerto Rico, Panama and in the Western Gulf of Mexico. Results for tropical cumulus clouds indicate excellent agreement between the cloud motion and the wind at the cloud base. The magnitude of the vector difference between the cloud motion and the cloud base wind is less than 1.3 m/sec for 67% of the cases with track lengths of 1 hour or longer. The cirrus cloud motions agreed best with the mean wind in the cloud layer with a vector difference of about 1.6 m/sec.

  11. Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 phase 1 studies

    PubMed Central

    Davies, Jeff K.; Gribben, John G.; Brennan, Lisa L.; Yuk, Dongin; Nadler, Lee M.

    2008-01-01

    We report the outcomes of 24 patients with high-risk hematologic malignancies or bone marrow failure (BMF) who received haploidentical bone marrow transplantation (BMT) after ex vivo induction of alloantigen-specific anergy in donor T cells by allostimulation in the presence of costimulatory blockade. Ninety-five percent of evaluable patients engrafted and achieved full donor chimerism. Despite receiving a median T-cell dose of 29 ×106/kg, only 5 of 21 evaluable patients developed grade C (n = 4) or D (n = 1) acute graft-versus-host disease (GVHD), with only one attributable death. Twelve patients died from treatment-related mortality (TRM). Patients reconstituted T-cell subsets and immunoglobulin levels rapidly with evidence of in vivo expansion of pathogen-specific T cells in the early posttransplantation period. Five patients reactivated cytomegalovirus (CMV), only one of whom required extended antiviral treatment. No deaths were attributable to CMV or other viral infections. Only 1 of 12 evaluable patients developed chronic GVHD. Eight patients survive disease-free with normal performance scores (median follow-up, 7 years). Thus, despite significant early TRM, ex vivo alloanergization can support administration of large numbers of haploidentical donor T cells, resulting in rapid immune reconstitution with very few viral infections. Surviving patients have excellent performance status and a low rate of chronic GVHD. PMID:18617635

  12. Cliffs Minerals, Inc. Eastern Gas Shales Project, Ohio No. 6 series: Gallia County. Phase II report. Preliminary laboratory results

    SciTech Connect

    1980-06-01

    The US Department of Energy is funding a research and development program entitled the Eastern Gas Shales Project designed to increase commercial production of natural gas in the eastern United States from Middle and Upper Devonian Shales. On September 28, 1978 the Department of Energy entered into a cooperative agreement with Mitchell Energy Corporation to explore Devonian shale gas potential in Gallia County, Ohio. Objectives of the cost-sharing contract were the following: (1) to select locations for a series of five wells to be drilled around the periphery of a possible gas reservoir in Gallia County, Ohio; (2) to drill, core, log, case, fracture, clean up, and test each well, and to monitor production from the wells for a five-year period. This report summarizes the procedures and results of core characterization work performed at the Eastern Gas Shales Project Core Laboratory on core retrieved from the Gallia County EGSP wells, designated OH No. 6/1, OH No. 6/2, OH No. 6/3, OH No. 6/4, and OH No. 6/5. Characterization work performed includes photographic logs, fracture logs, measurements of core color variation, and stratigraphic interpretation of the cored intervals. In addition the following tests were performed by Michigan Technological University to obtain the following data: directional ultrasonic velocity; directional tensile strength, strength in point load; trends of microfractures; and hydraulic fracturing characteristics.

  13. Results of gas-fired flash-smelting tests. Phase 1-3. Topical technical report, November 1987-April 1989

    SciTech Connect

    Pusateri, J.F.

    1990-06-01

    A natural gas-fired burner for the HRD FLAME REACTOR Process was designed and successfully tested on over 450 tons of Electric Arc Furnace (EAF) dust, and over a wide range of operating conditions. The coal/coke-fired FLAME REACTOR Process has already been demonstrated as an efficient and economic means of recovering zinc from EAF dust as a salable oxide product, and a salable nonhazardous, iron-rich slag product. The results of the work indicate that the natural gas-fired process has a higher zinc capacity for a given reactor size, with zinc recoveries 5-10 percentage points higher than coal/coke processing at high throughputs. Gas-fired capital costs are about 15% less than coal for a 20,000 STPY EAF dust plant. Smaller plants show even higher break-even costs. Net processing costs are about $100/ton of EAF dust, which is extremely competitive with land-filling and other recycling options.

  14. 30 CFR 203.40 - Which leases are eligible for royalty relief as a result of drilling a deep well or a phase 1...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... a result of drilling a deep well or a phase 1 ultra-deep well? 203.40 Section 203.40 Mineral... MANAGEMENT RELIEF OR REDUCTION IN ROYALTY RATES OCS Oil, Gas, and Sulfur General § 203.40 Which leases are... may receive an RSV under §§ 203.41 through 203.44, and may receive an RSS under §§ 203.45 through...

  15. 30 CFR 203.40 - Which leases are eligible for royalty relief as a result of drilling a deep well or a phase 1...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... a result of drilling a deep well or a phase 1 ultra-deep well? 203.40 Section 203.40 Mineral... MANAGEMENT RELIEF OR REDUCTION IN ROYALTY RATES OCS Oil, Gas, and Sulfur General § 203.40 Which leases are... may receive an RSV under §§ 203.41 through 203.44, and may receive an RSS under §§ 203.45 through...

  16. Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project, UAS Control and Non-Payload Communication System Phase-1 Flight Test Results

    NASA Technical Reports Server (NTRS)

    Griner, James H.

    2014-01-01

    NASA's UAS Integration in the NAS project, has partnered with Rockwell Collins to develop a concept Control and Non-Payload Communication (CNPC) system prototype radio, operating on recently allocated UAS frequency spectrum bands. This prototype radio is being used to validate initial proposed performance requirements for UAS control communications. This presentation will give an overview of the current status of the prototype radio development, and results from phase 1 flight tests conducted during 2013.

  17. Effect of weekly adefovir (PMEA) infusions on HIV-1 virus load: results of a phase I/II study.

    PubMed

    Kamp, W; Schokker, J; Cambridge, E; De Jong, S; Schuurman, R; De Groot, T; Boucher, C A

    1999-01-01

    The compound 9-(2-phosphonylmethoxyethyl)adenine (adefovir; PMEA) is a potent inhibitor of a number of viruses in vitro, such as human immunodeficiency virus (HIV) type 1 and 2, herpes simplex virus (HSV) type 1 and 2, human papillomavirus virus (HBV) and Epstein-Barr virus (EBV). Adefovir also proved to be effective in vivo against feline immunodeficiency virus (FIV) in cats and simian immunodeficiency virus (SIV) in rhesus monkeys. In an open, non-placebo-controlled trial the antiviral activity of weekly doses of adefovir in nine patients with AIDS or AIDS-related complex was studied for a period of 11 weeks. CD4 cell counts at baseline were between 10 and 450 cells/mm3, HIV-1 RNA levels at baseline were between 24,210 copies/ml and 406,197 copies/ml. The drug was administered intravenously at a dose of 1000 mg every week and plasma viral load was assessed at multiple points during the study. Administration of adefovir was tolerated well and no severe side effects were seen. The response to adefovir treatment differed widely between patients. The increase in CD4 cell count at end point ranged from -40 to 120 cell/mm3. The lowest HIV RNA levels were measured after 3-5 days, showing an increase thereafter. The nadir in viral load was achieved after 2 weeks, with a mean viral load decline of 0.7 from baseline. The decrease of the HIV RNA level at end point ranged from -0.3 log10 to 1.8 log10 with a mean decrease of 0.4 log10. Our results indicate that adefovir given intravenously once weekly has a short-lasting initial antiviral effect. The effect of more frequent dosing requires further evaluation. If adefovir is to be useful clinically, it needs to be combined with other antiviral agents.

  18. Results of the flowmeter-injection test in the Long Valley Exploratory Well (Phase II), Long Valley, California

    USGS Publications Warehouse

    Morin, R.H.; Sorey, M.L.; Jacobson, R.D.

    1993-01-01

    Bayboro Harbor and the Port of St. Petersburg, Florida, form a manmade basin adjacent to Tampa Bay that may supply turbid water to the bay and subsequently affect light penetration in water in the bay. To address concerns about the nature and extent of this potential problem, resuspension of bottom sediments, sedimentation, and tributary storm discharge in the basin were studied. Study results indicated that tidal currents, wind waves, and seiche motions do not resuspend bottom sediments. The maneuvering of a cruise ship in the port resuspended bottom sediments, but these sediments settled within 2 hours. Tidal currents and wave action were not large enough o prevent the resuspended sediments from settling in the basin. Analysis of bathymetric surveys of the port made in 1981, 1986, 1987, and 1989 indicates that the cruise ship has deepened the port along its route and that the displaced sediment has been deposited elsewhere within the port. The storm discharge from two tributaries and the effect of tributary storm runoff on the water quality of the harbor were studied during a storm on November 9, 1989. Booker Creek, which drains an urban watershed, was stratified with a thin layer of turbid freshwater flowing into the harbor over a layer of less turbid saltwater. Salt Creek, which primarily drains Lake Maggiore, was only partially stratified and was less turbid. The turbid water from the creeks increased the turbidity only slightly in the harbor, probably because of mixing with less turbid water and particle settling. Thus, the basin provides mixing and settling, which diminish and eliminate the potentially adverse effect on Tampa Bay from tributary storm runoff and large vessel traffic in the basin.

  19. Lisdexamfetamine Dimesylate for Adults with Moderate to Severe Binge Eating Disorder: Results of Two Pivotal Phase 3 Randomized Controlled Trials

    PubMed Central

    McElroy, Susan L; Hudson, James; Ferreira-Cornwell, M Celeste; Radewonuk, Jana; Whitaker, Timothy; Gasior, Maria

    2016-01-01

    The efficacy and safety of lisdexamfetamine dimesylate (LDX) vs placebo in binge eating disorder (BED) was evaluated in two multicenter, double-blind, placebo-controlled trials. Adults (study 1, n=383; study 2, n=390) meeting DSM-IV-TR BED criteria were randomized (1:1) to placebo or LDX (50 or 70 mg/day) dose titration; optimized doses were maintained to the end of double-blind treatment (week 12/early termination). Change from baseline in binge eating days/week at weeks 11−12 (primary efficacy endpoint) was assessed with mixed-effects models for repeated measures. Secondary endpoints related to binge eating and medical parameters, safety, and treatment compliance were also assessed. Least squares mean (95% CI) treatment differences for change from baseline binge eating days/week at weeks 11–12 significantly favored LDX (study 1: –1.35 [–1.70, –1.01] study 2: –1.66 [–2.04, –1.28] both P<0.001). In both studies, treatment-emergent adverse events (TEAEs) reported by ⩾10% of LDX participants were dry mouth, insomnia, and headache. Serious TEAEs occurred in two (1.1%) placebo participants in each study and in three (1.6%) and one (0.6%) LDX participants in study 1 and study 2, respectively. Across studies, mean increases from baseline at week 12/early termination with LDX for pulse and systolic and diastolic blood pressure ranged from 4.41–6.31 b.p.m. and 0.2–1.45 and 1.06–1.83 mm Hg, respectively. LDX (50 and 70 mg/day) was superior to placebo in decreasing binge eating days/week from baseline and improving binge eating–related key secondary endpoints. Safety results appear consistent with the known safety profile of LDX. PMID:26346638

  20. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma-long-term results of phase III RTOG 85-31

    SciTech Connect

    Pilepich, Miljenko V. . E-mail: mpilepich@mednet.ucla.edu; Winter, Kathryn; Lawton, Colleen A.; Krisch, Robert E.; Wolkov, Harvey B.; Movsas, Benjamin; Hug, Eugen B.; Asbell, Sucha O.; Grignon, David

    2005-04-01

    Purpose: Radiation Therapy Oncology Group protocol 85-31 was designed to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy (RT). Methods and Materials: Eligible patients were those with palpable primary tumor extending beyond the prostate (clinical Stage T3) or those with regional lymphatic involvement. Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and/or seminal vesicle involvement was documented histologically. Stratification was based on histologic differentiation, nodal status, acid phosphatase status, and prior prostatectomy. The patients were randomized to either RT and adjuvant goserelin (Arm I) or RT alone followed by observation and application of goserelin at relapse (Arm II). In Arm I, the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression. Results: Between 1987 and 1992, when the study was closed, 977 patients were entered: 488 to Arm I and 489 to Arm II. As of July 2003, the median follow-up for all patients was 7.6 years and for living patients was 11 years. At 10 years, the absolute survival rate was significantly greater for the adjuvant arm than for the control arm: 49% vs. 39%, respectively (p = 0.002). The 10-year local failure rate for the adjuvant arm was 23% vs. 38% for the control arm (p <0.0001). The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24% vs. 39% (p <0.001) and 16% vs. 22% (p = 0.0052), respectively, both in favor of the adjuvant arm. Conclusion: In a population of patients with unfavorable prognosis carcinoma of the prostate, androgen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute

  1. Intra-Erythrocyte Infusion of Dexamethasone Reduces Neurological Symptoms in Ataxia Teleangiectasia Patients: Results of a Phase 2 Trial

    PubMed Central

    2014-01-01

    Background Ataxia Teleangiectasia [AT] is a rare neurodegenerative disease characterized by early onset ataxia, oculocutaneous teleangiectasias, immunodeficiency, recurrent infections, radiosensitivity and proneness to cancer. No therapies are available for this devastating disease. Recent observational studies in few patients showed beneficial effects of short term treatment with betamethasone. To avoid the characteristic side effects of long-term administration of steroids we developed a method for encapsulation of dexamethasone sodium phosphate (DSP) into autologous erythrocytes (EryDex) allowing slow release of dexamethasone for up to one month after dosing. Aims of the study were: the assessment of the effect of EryDex in improving neurological symptoms and adaptive behaviour of AT patients; the safety and tolerability of the therapy. Methods Twenty two patients (F:M = 1; mean age 11.2 ± 3.5) with a confirmed diagnosis of AT and a preserved or partially supported gait were enrolled for the study. The subjects underwent for six months a monthly infusion of EryDex. Ataxia was assessed by the International Cooperative Ataxia Rating Scale (ICARS) and the adaptive behavior by Vineland Adaptive Behavior Scales (VABS). Clinical evaluations were performed at baseline and 1, 3, and 6 months. Results An improvement in ICARS (reduction of the score) was detected in the intention-to-treat (ITT) population (n = 22; p = 0.02) as well as in patients completing the study (per protocol PP) (n = 18; p = 0.01), with a mean reduction of 4 points (ITT) or 5.2 points (PP). When compared to baseline, a significant improvement were also found in VABS (increase of the score) (p < 0.0001, ITT, RMANOVA), with statistically significant increases at 3 and 6 months (p < 0.0001). A large inter-patient variability in the incorporation of DSP into erythrocytes was observed, with an evident positive effect of higher infusion dose on ICARS score decline

  2. Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: Results of a multicenter Phase III study

    SciTech Connect

    Sanguineti, Giuseppe . E-mail: gisangui@utmb.edu; Richetti, Antonella; Bignardi, Mario; Corvo, Renzo; Gabriele, Pietro; Sormani, Maria Pia; Antognoni, Paolo

    2005-03-01

    Purpose: To determine whether, in the postoperative setting, accelerated fractionation (AF) radiotherapy (RT) yields a superior locoregional control rate compared with conventional fractionation (CF) RT in locally advanced squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx. Methods and materials: Patients from four institutions with one or more high-risk features (pT4, positive resection margins, pN >1, perineural/lymphovascular invasion, extracapsular extension, subglottic extension) after surgery were randomly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF. Accelerated fractionation consisted of a 'biphasic concomitant boost' schedule, with the boost delivered during the first and last weeks of treatment, to deliver 64 Gy in 5 weeks. Informed consent was obtained. The primary endpoint of the study was locoregional control. Analysis was on an intention-to-treat basis. Results: From March 1994 to August 2000, 226 patients were randomized. At a median follow-up of 30.6 months (range, 0-110 months), 2-year locoregional control estimates were 80% {+-} 4% for CF and 78% {+-} 5% for AF (p = 0.52), and 2-year overall survival estimates were 67% {+-} 5% for CF and 64% {+-} 5% for AF (p = 0.84). The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis. However, interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF (hazard ratio = 0.5, 95% confidence interval 0.2-1.1). Fifty percent of patients treated with AF developed confluent mucositis, compared with only 27% of those treated with CF (p = 0.006). However, mucositis duration was not different between arms. Although preliminary, actuarial Grade 3+ late toxicity estimates at 2 years were 18% {+-} 4% and 27% {+-} 6% for CF

  3. Layered Na‐Ion Cathodes with Outstanding Performance Resulting from the Synergetic Effect of Mixed P‐ and O‐Type Phases

    PubMed Central

    Keller, Marlou

    2015-01-01

    Herein, the synthesis of new quaternary layered Na‐based oxides of the type NaxMnyNizFe0.1Mg0.1O2 (0.67≤ x ≤ 1.0; 0.5≤ y ≤ 0.7; 0.1≤ z ≤ 0.3) is described. The synthesis can be tuned to obtain P2‐ and O3‐type as well as mixed P‐/O‐type phases as demonstrated by structural, morphological, and electrochemical properties characterization. Although all materials show good electrochemical performance, the simultaneous presence of the P‐ and O‐type phases is found to have a synergetic effect resulting in outstanding performance of the mixed phase material as a sodium‐ion cathode. The mixed P3/P2/O3‐type material, having an average elemental composition of Na0.76Mn0.5Ni0.3Fe0.1Mg0.1O2, overcomes the specific drawbacks associated with the P2‐ and O3‐type materials, allowing the outstanding electrochemical performance. In detail, the mixed phase material is able to deliver specific discharge capacities of up to 155 mAh g−1 (18 mA g−1) in the potential range of 2.0–4.3 V. In the narrower potential range of 2.5–4.3 V the material exhibits high average discharge potential (3.4 V versus Na/Na+), exceptional average coulombic efficiencies (>99.9%), and extraordinary capacity retention (90.2% after 601 cycles). The unexplored class of P‐/O‐type mixed phases introduces new perspectives for the development of layered positive electrode materials and powerful Na‐ion batteries. PMID:27134617

  4. IVA: Improving Vocational Administration.

    ERIC Educational Resources Information Center

    EPD Consortium D, Richardson, TX.

    These six instructional units are intended to provide instructors of vocational education administration with a systematic package of materials for their programs of preservice and/or inservice instruction and to provide materials which could be reproduced for learner use. These units cover the following subject matter: (1) federal legislation…

  5. Water- and Air-Quality Monitoring of the Sweetwater Reservoir Watershed, San Diego County, California-Phase One Results, Continued, 1999-2001

    USGS Publications Warehouse

    Mendez, Gregory O.; Foreman, William T.; Sidhu, Jagdeep S.; Majewski, Michael S.

    2007-01-01

    In 1998, the U.S. Geological Survey, in cooperation with the Sweetwater Authority, began a study to assess the overall health of the Sweetwater watershed with respect to chemical contamination. The study included regular sampling of air and water at Sweetwater Reservoir for chemical contaminants, including volatile organic compounds, polycyclic aromatic hydrocarbons, pesticides, and major and trace elements. Background water samples were collected at Loveland Reservoir for volatile organic compounds and pesticides. The purpose of this study was to monitor changes in contaminant composition and concentration in the air and water resulting from the construction and operation of State Route 125 near Sweetwater Reservoir. To accomplish this, the study was divided into two phases. Phase One sampling was designed to establish baseline conditions for target compounds in terms of detection frequency and concentration in air and water. Phase Two sampling is planned to continue at the established monitoring sites during and after construction of State Route 125 to assess the chemical impact this roadway alignment project may have on the water quality in the reservoir. In addition to the ongoing data collection, several special studies were initiated to assess the occurrence of specific chemicals of concern, such as low-use pesticides, trace metals, and wastewater compounds. This report describes the study design, and the sampling and analytical methods, and presents the results for the second and third years of the study (October 1999 to September 2001). Data collected during the first year of sampling (October 1998 to September 1999) were published in 2002.