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Sample records for factor iiib generates

  1. A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1

    PubMed Central

    Miura, Kiyonori; Miura, Shoko; Yoshiura, Koh-ichiro; Seminara, Stephanie; Hamaguchi, Daisuke; Niikawa, Norio; Masuzaki, Hideaki

    2010-01-01

    Fibroblast growth factor receptor 1 (FGFR1) is one of the causative genes for Kallmann syndrome (KS), which is characterized by isolated hypogonadotropic hypogonadism with anosmia/hyposmia. The third immunoglobulin-like domain (D3) of FGFR1 has the isoforms FGFR1-IIIb and FGFR1-IIIc, which are generated by alternative splicing of exons 8A and 8B, respectively. To date, the only mutations to have been identified in D3 of FGFR1 are in exon 8B. We performed mutation analysis of FGFR1 in a 23-year-old female patient with KS and found a missense mutation (c.1072C>T) in exon 8A of FGFR1. The c.1072C>T mutation was not detected in her family members or in 220 normal Japanese and 100 Caucasian female controls. No mutation in other KS genes, KS 1, prokineticin-2, prokineticin receptor-2 and FGF-8 was detected in the affected patient or in her family members. Therefore, this is the first case of KS carrying a de novo missense mutation in FGFR1 exon 8A, suggesting that isoform FGFR1-IIIb, as well as isoform FGFR1-IIIc, plays a crucial role in the pathogenesis of KS. PMID:20139426

  2. Factors associated with allergic rhinitis in children and adolescents from northern Mexico: International Study of Asthma and Allergies in Childhood Phase IIIB.

    PubMed

    González-Díaz, Sandra N; Del Río-Navarro, Blanca E; Pietropaolo-Cienfuegos, Dino R; Escalante-Domínguez, Alberto J; García-Almaraz, Roberto G; Mérida-Palacio, Valente; Berber, Arturo

    2010-01-01

    The epidemiology of allergic diseases has not been studied extensively in Mexico. The present study, based on the International Study of Asthma and Allergies in Childhood Phase IIIB survey, reports the prevalence of allergic rhinitis and the associated risk factors in the pediatric population in four cities in northern Mexico. Children (6-7 years old) and adolescents (13-14 years old) in public elementary and secondary schools were surveyed in 2002 and 2003. The subjects were chosen randomly from Ciudad Victoria, Mexicali, Monterrey, and Tijuana. The following categories were analyzed: occurrence of rhinitis symptoms (currently or in the last 12 months), rhinoconjunctivitis symptoms, a previous diagnosis of allergic rhinitis, and relevant environmental factors. Factors associated with rhinitis that were identified previously with the chi-squared test were analyzed using logistic regression. The number of valid questionnaires was 10,892 for schoolchildren and 12,299 for adolescents. In 6- to 7-year-old children, the following frequencies were determined: rhinitis (ever), 27.9%; current rhinitis, 24.2%; rhinoconjunctivitis, 9.2%; and diagnosis of allergic rhinitis, 5.5%. The corresponding frequencies in 13- to 14-year-old children were 33.3, 34.1, 18.4, and 3.8%. In both 6- to 7-year-old and 13- to 14-year-old children, all rhinitis items were associated with asthma symptoms, dermatitis symptoms, paracetamol consumption, and maternal smoking (odds ratio, >1; p < 0.05). The main risk factors associated with allergic rhinitis symptoms in children and adolescents from cities in northern Mexico were other allergic conditions, paracetamol consumption, and passive smoking.

  3. Chemical vapor deposition of group IIIB metals

    DOEpatents

    Erbil, Ahmet

    1989-01-01

    Coatings of Group IIIB metals and compounds thereof are formed by chemical vapor deposition, in which a heat decomposable organometallic compound of the formula (I) ##STR1## where M is a Group IIIB metal, such as lanthanum or yttrium and R is a lower alkyl or alkenyl radical containing from 2 to about 6 carbon atoms, with a heated substrate which is above the decomposition temperature of the organometallic compound. The pure metal is obtained when the compound of the formula I is the sole heat decomposable compound present and deposition is carried out under nonoxidizing conditions. Intermetallic compounds such as lanthanum telluride can be deposited from a lanthanum compound of formula I and a heat decomposable tellurium compound under nonoxidizing conditions.

  4. Chemical vapor deposition of group IIIB metals

    DOEpatents

    Erbil, A.

    1989-11-21

    Coatings of Group IIIB metals and compounds thereof are formed by chemical vapor deposition, in which a heat decomposable organometallic compound of the formula given in the patent where M is a Group IIIB metal, such as lanthanum or yttrium and R is a lower alkyl or alkenyl radical containing from 2 to about 6 carbon atoms, with a heated substrate which is above the decomposition temperature of the organometallic compound. The pure metal is obtained when the compound of the formula 1 is the sole heat decomposable compound present and deposition is carried out under nonoxidizing conditions. Intermetallic compounds such as lanthanum telluride can be deposited from a lanthanum compound of formula 1 and a heat decomposable tellurium compound under nonoxidizing conditions.

  5. Theory of type IIIb solar radio bursts

    NASA Technical Reports Server (NTRS)

    Smith, R. A.; De La Noe, J.

    1976-01-01

    During the initial space-time evolution of an electron beam injected into the corona, the strong beam-plasma interaction occurs at the head of the beam, leading to the amplification of a quasi-monochromatic large-amplitude plasma wave that stabilizes by trapping the beam particles. Oscillation of the trapped particles in the wave troughs amplifies sideband electrostatic waves. The sidebands and the main wave subsequently decay to observable transverse electromagnetic waves through the parametric decay instability. This process gives rise to the elementary striation bursts. Owing to velocity dispersion in the beam and the density gradient of the corona, the entire process may repeat at a finite number of discrete plasma levels, producing chains of elementary bursts. All the properties of the type IIIb bursts are accounted for in the context of the theory.

  6. Genistein reduces lysosomal storage in peripheral tissues of mucopolysaccharide IIIB mice.

    PubMed

    Malinowska, Marcelina; Wilkinson, Fiona L; Bennett, William; Langford-Smith, Kia J; O'Leary, H Angharad; Jakobkiewicz-Banecka, Joanna; Wynn, Rob; Wraith, J Ed; Wegrzyn, Grzegorz; Bigger, Brian W

    2009-11-01

    Mucopolysaccharidosis type IIIB (Sanfilippo syndrome) is a lysosomal storage disease caused by a genetic defect in the production of alpha-N-acetylglucosaminidase. This results in lysosomal and extracellular accumulation of the undegraded glycosaminoglycan (GAG) substrate, heparan sulphate. Affected patients show progressive CNS degeneration characterised by mental retardation, hyperactivity and seizures, with death usually in the mid teens to early twenties. Visceral organ storage is also present but is relatively mild compared to other MPS diseases storing similar substrates. No treatments currently exist for MPS IIIB. Genistein is a broad spectrum protein tyrosine kinase inhibitor which acts on several different growth factor receptors, notably EGF and IGF receptors, both of which are important for proteoglycan synthesis. Recent work has shown that genistein can reduce GAG synthesis in patients' fibroblasts in vitro and there is evidence in patients to suggest that it may be an effective substrate reduction therapy agent for MPS III. Here we have tested the dose responses of MPS IIIB mice to daily sub-chronic dosing of genistein in half log increments compared to carrier over 8 weeks. We show clear reductions in liver lysosome compartment size in both sexes and significant dose dependent improvements in total liver GAGs and hair morphology in male MPS IIIB animals following genistein treatment. Male MPS IIIB mice exhibited considerably more liver storage than females and responded better to treatment. No changes in total GAGs, lysosomal size or reactive astrogliosis in the brain cortex were observed after 8 weeks of treatment despite evidence that genistein can cross the blood brain barrier. This is the first demonstration of genistein treatment in MPS models in vivo. PMID:19632871

  7. The neurobehavioral phenotype in mucopolysaccharidosis Type IIIB: An exploratory study

    PubMed Central

    Shapiro, E.; King, K.; Ahmed, A.; Rudser, K.; Rumsey, R.; Yund, B.; Delaney, K.; Nestrasil, I.; Whitley, C.; Potegal, M.

    2016-01-01

    Objectives Our goal was to describe the neurobehavioral phenotype in mucopolysaccharidosis Type IIIB (MPS IIIB). Parents report that behavioral abnormalities are a major problem in MPS III posing serious challenges to parenting and quality-of-life for both patient and parent. Our previous research on MPS IIIA identified autistic symptoms, and a Klüver-Bucy-type syndrome as indicated by reduced startle and loss of fear associated with amygdala atrophy. We hypothesized that MPS IIIB would manifest similar attributes when assessed with the same neurobehavioral protocol. Methods Ten patients with MPS IIIB were compared with 9 MPS IIIA patients, all older than 6. 8 younger children with Hurler syndrome (1H) were chosen as a comparison group for the Risk Room procedure; MPS IH does not directly affect social/emotional function and these younger children were closer to the developmental level of the MPS IIIB group. To examine disease severity, cognitive ability was assessed. Four evaluations were used: the Risk Room procedure (to measure social-emotional characteristics, especially fear and startle responses), the Autism Diagnostic Observation Schedule (ADOS), the Sanfilippo Behavior Rating Scale (SBRS), and amygdala brain volumes calculated from manually-traced MRI images. Results The two groups are equivalent in severity and show severe cognitive impairment. On the ADOS, the MPS IIIB patients exhibited the same autistic features as IIIA. The IIIB means differed from MPS IH means on most measures. However, the IIIB group did not approach the Risk Room stranger, like the MPS IH group who kept their distance, but unlike the IIIA group who showed no fear of the stranger. On the SBRS, the MPS IIIB patients were described as more inattentive and more fearful, especially of new people than the MPS IIIA. Onsets of some disease characteristics appeared more closely spaced and slightly earlier in MPS IIIB than IIIA. Conclusions On most behavioral measures, MPS IIIB patients did

  8. Observations and interpretation of solar decameter type IIIb radio bursts

    NASA Astrophysics Data System (ADS)

    Krishan, V.; Subramanian, K. R.; Sastry, C. V.

    1980-06-01

    Observations on the time structure of short duration, narrow band solar decameter type IIIb radio bursts are presented along with a theoretical model accounting for various features of the bursts. In contrast to the theory of Smith and de la Noe (1976), the electromagnetic modes of the plasma are immersed in the electric and magnetic fields in the presented theory, and the electric field enters at the single particle level and thus is accounted for in a more exact manner. In addition, the direction of propagation of the type IIIb radio burst is more clearly indicated by this theory than by Smith and de la Noe (1976).

  9. Proper hepatic pedicle clamping during hepatectomy is associated with improved postoperative long-term prognosis in patients with AJCC stage IIIB hepatocellular carcinoma

    PubMed Central

    Guo, Lei; Zhang, Bo; Lin, Zhenhai; Zhang, Jubo; Ye, Qinghai

    2016-01-01

    Intermittent hepatic pedicle clamping (HPC) is often performed during hepatectomy. Whether it affects the long-term prognosis of hepatocellular carcinoma (HCC) patients is still controversial. This study evaluated the impact of HPC in patients with different stages of HCC. The study included 1401 patients who underwent hepatectomy in the primary cohort with 129 AJCC stage IIIB HCC patients; there were 80 AJCC stage IIIB HCC patients in the validation cohort. In each cohort, patients were placed in the long-term HPC (LTHPC) group or the short-term HPC (STHPC) group based on the cut-off time of HPC estimated by the receiver-operating characteristic (ROC) curve. Although HPC did not show significant effects on the prognosis of stage I–IIIA HCC patients in the primary cohort, 1−, 3−, and 5-year overall survival (OS) and recurrence-free survival (RFS) rates of stage IIIB HCC patients who received LTHPC (HPC time > 12 minutes) were significantly higher than those with STHPC (HPC time ≤ 12 minutes or received no HPC), similar in the validation cohort. Multivariate analysis demonstrated HPC time was an independent protective factor for RFS and OS in stage IIIB HCC patients. Herein, we report that proper HPC improved the postoperative prognosis of stage IIIB HCC patients and served as an independent protective factor. PMID:27027437

  10. Novel mutation detection of fibroblast growth factor receptor 1 (FGFR1) gene, FGFR2IIIa, FGFR2IIIb, FGFR2IIIc, FGFR3, FGFR4 gene for craniosynostosis: A prospective study in Asian Indian patient

    PubMed Central

    Barik, Mayadhar; Bajpai, Minu; Malhotra, Arun; Samantaray, Jyotish Chandra; Dwivedi, Sadananda; Das, Sambhunath

    2015-01-01

    Background: Craniosynostosis (CS) syndrome is an autosomal dominant condition classically combining craniosynostosis and non-syndromic craniosynostosis with digital anomalies of the hands and feet. The majority of cases are caused by heterozygous mutations in the third immunoglobulin-like domain (IgIII) of FGFR2, whilst a larger number of cases can be attributed to mutations outside this region of the protein. Aims: To find out the FGFR1, FGFR2, FGFR3 and FGFR4 gene in craniosynostosis syndrome. Settings and Design: A hospital based prospective study. Materials and Methods: Prospective analysis of clinical records of patients registered in CS clinic from December 2007 to January 2015 was done in patients between 4 months to 13 years of age. We have performed genetic findings in a three generation Indian family with Craniosynostosis syndrome. Results: We report for the first time the clinical and genetic findings in a three generation Indian family with Craniosynostosis syndrome caused by a heterozygous missense mutation, Thr 392 Thr and ser 311 try, located in the IgII domain of FGFR2. FGFR 3 and 4 gene basis syndrome was eponymously named. Genetic analysis demonstrated that 51/56 families to be unrelated. In FGFR3 gene 10/TM location of 1172 the nucleotide changes C>A, Ala 391 Glu 19/56 and Exon-19, 5q35.2 at conserved linker region the changes occurred pro 246 Arg in 25/56 families. Conclusions: Independent genetic origins, but phenotypic similarities in the 51 families add to the evidence supporting the theory of selfish spermatogonial selective advantage for this rare gain-of-function FGFR2 mutation. PMID:26557159

  11. Instruments, methods, statistics, plasmaphysical interpretation of type IIIb bursts

    NASA Astrophysics Data System (ADS)

    Urbarz, H. W.

    Type-IIIb solar bursts in the m-dkm band and the methods used to study them are characterized in a review of recent research. The value of high-resolution spectrographs (with effective apertures of 1000-100,000 sq m, frequency resolution 20 kHz, and time resolution 100 msec) in detecting and investigating type-IIIb bursts is emphasized, and the parameters of the most important instruments are listed in a table. Burst spectra, sources, polarization, flux, occurrence, and association with other types are discussed and illustrated with sample spectra, tables, and histograms. The statistics of observations made at Weissenau Observatory (Tuebingen, FRG) from August, 1978, through December, 1979, are considered in detail. Theories proposed to explain type-III and type-IIIb bursts are summarized, including frequency splitting (FS) of the Langmuir spectrum, FS during the transverse-wave conversion process, FS during propagation-effect transverse-wave escape, and discrete source regions with different f(p) values.

  12. Persistence Factors of First-Generation Learners

    ERIC Educational Resources Information Center

    Braswell, Tawanda M.

    2010-01-01

    This dissertation utilized a qualitative narrative case study method to explore the unknown factors and elements of perseverance in spite of adversity and crisis. The study documented the lives of five African American women in order to describe, understand, and explain the central research question of how and why some first-generation learners…

  13. Membrane-permeabilizing activities of Bacillus thuringiensis coleopteran-active toxin CryIIIB2 and CryIIIB2 domain I peptide.

    PubMed Central

    Von Tersch, M A; Slatin, S L; Kulesza, C A; English, L H

    1994-01-01

    Bacillus thuringiensis toxin CryIIIB2 exhibits activity against two agriculturally important pests, the Colorado potato beetle, Leptinotarsa decemlineata, and the Southern corn rootworm, Diabrotica undecimpunctata. CryIIIB2 shows significant structural similarity to Colorado potato beetle-active toxin CryIIIA, whose crystal structure has been determined elsewhere [J. Li, J. Carrol, and D. J. Ellar, Nature (London) 353:815-821, 1991]. A clone limited to the putative 7-alpha-helical bundle domain I peptide of CryIIIB2 was constructed by PCR. The truncated protein was expressed at high levels in Escherichia coli. Domain I peptide was isolated and compared with native CryIIIB2 toxin in promoting ion efflux from synthetic phospholipid vesicles and formation of ion channels in black lipid membranes. The results showed that CryIIIB2 domain I peptide is sufficient for ion channel formation and promotes ion efflux. Both native CryIIIB2 toxin and domain I peptide were inefficient channel-forming proteins that produced noisy ion channels of various conductance states. In ion efflux assays, native toxin promoted greater ion efflux from synthetic vesicles than did the truncated peptide. Images PMID:7527203

  14. [Tolerance of riluzole in a phase IIIb clinical trial].

    PubMed

    Lacomblez, L; Dib, M; Doppler, V; Faudet, A; Robin, V; Salachas, F; Bensimon, G; Meininger, V

    2002-01-01

    Within the framework of an early drug access programme launched in 1995, a multicentre open study was initiated in France in order to assess, inter alia, the safety of riluzole (50 mg twice a day) in a total of 2069 patients from 28 centres. This programme, a phase IIIb study with direct individual benefit, had two main objectives: to enable patients to receive riluzole therapy pending regulatory approval and commercial availability and to provide further data on the safety of riluzole in a broader ALS population. The most frequent adverse events related to riluzole treatment were: asthenia, nausea and elevation of serum transaminase levels. These observations, similar to data derived from previous pivotal clinical trials, confirm that riluzole has a satisfactory tolerability profile. PMID:12090150

  15. A Second Generation Nonlinear Factor Analysis.

    ERIC Educational Resources Information Center

    Etezadi-Amoli, Jamshid; McDonald, Roderick P.

    1983-01-01

    Nonlinear common factor models with polynomial regression functions, including interaction terms, are fitted by simultaneously estimating the factor loadings and common factor scores, using maximum likelihood and least squares methods. A Monte Carlo study gives support to a conjecture about the form of the distribution of the likelihood ratio…

  16. A Scenario for the Fine Structures of Solar Type IIIb Radio Bursts Based on Electron Cyclotron Maser Emission

    NASA Astrophysics Data System (ADS)

    Wang, C. B.

    2015-06-01

    A scenario based on electron cyclotron maser (ECM) emission is proposed for the fine structures of solar radio emission. It is suggested that under certain conditions modulation of the ratio between the plasma frequency and electron gyro frequency by ultra-low-frequency waves, which is a key parameter for excitation of ECM instability, may lead to the intermittent emission of radio waves. As an example, the explanation for the observed fine-structure components in the solar Type IIIb bursts is discussed in detail. Three primary issues of Type IIIb bursts are addressed: (1) the physical mechanism that results in intermittent emission elements that form a chain in the dynamic spectrum of Type IIIb bursts, (2) the cause of split pairs (or double stria) and triple stria, and (3) why only IIIb-III bursts are observed in the events of fundamental harmonic pair emission whereas IIIb-IIIb or III-IIIb bursts are very rarely observed.

  17. Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer

    ClinicalTrials.gov

    2014-08-04

    Adenocarcinoma of the Lung; Bronchoalveolar Cell Lung Cancer; Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  18. Type IIIb bursts and their fine structure in frequency band 18-30 MHz

    NASA Astrophysics Data System (ADS)

    Melnik, V. N.; Rucker, H. O.; Konovalenko, A. A.; Shevchuk, N. V.; Abranin, E. P.; Dorovskyy, V. V.; Lecacheux, A.

    2010-01-01

    This paper deals with Type IIIb bursts, which were observed in the frequency band from 18 to 30 MHz. These bursts have fine frequency structures contrary to usual Type III bursts. The main properties of Type IIIb bursts such as number of striae in a burst, their frequency drift rates, durations, frequency widths of stria, emission fluxes are presented. It is also shown that parameters of stria bursts depend on the position of active areas on the solar disk.

  19. Cross-reactive lysis of human targets infected with prototypic and clinical human immunodeficiency virus type 1 (HIV-1) strains by murine anti-HIV-1 IIIB env-specific cytotoxic T lymphocytes.

    PubMed Central

    Chada, S; DeJesus, C E; Townsend, K; Lee, W T; Laube, L; Jolly, D J; Chang, S M; Warner, J F

    1993-01-01

    To evaluate the ability of murine anti-human immunodeficiency virus type 1 (HIV-1) IIIB env cytotoxic T lymphocytes (CTL) to recognize and lyse HIV-1-infected cells, we have constructed a human cell line (Hu/Dd) expressing both the CD4 receptor and the murine H-2Dd major histocompatibility complex (MHC) class I protein. This cell line can be productively infected with HIV-1 and can also function as a target for murine CD8+, class I MHC-restricted CTL directed against the envelope glycoprotein of HIV-1 IIIB. The ability of BALB/c anti-HIV-1 IIIB env CTL to specifically recognize and lyse Hu/Dd target cells infected with divergent HIV-1 strains was tested by using both prototypic and clinical HIV-1 strains. CTL generated by immunization of mice with syngeneic cells expressing either the native or V3 loop-deleted (delta V3) envelope glycoprotein from HIV-1 IIIB were able to recognize and specifically lyse Hu/Dd target cells infected with the HIV-1 prototypic isolates IIIB, MN, WMJ II, SF2, and CC as well as several HIV-1 clinical isolates. These results demonstrate that CTL determinants for HIV-1 env exist outside the hypervariable V3 region, anti-HIV-1 IIIB env CTL appear to recognize common determinants on diverse HIV-1 strains, and classification of HIV-1 strains based on neutralizing antibody reactivities does not appear to correspond to CTL recognition and lysis. The results suggest that the cell-mediated components of the immune system may have a broader recognition of divergent HIV-1 strains than do the humoral components. Images PMID:8497058

  20. Combined type IIIB with bilateral type I thyroplasty for pitch lowering with maintenance of vocal fold tension

    PubMed Central

    Hoffman, Matthew R.; Devine, Erin E.; Remacle, Marc; Ford, Charles N.; Wadium, Elizabeth; Jiang, Jack J.

    2013-01-01

    Objective To evaluate type IIIB thyroplasty using the excised larynx bench apparatus and determine how altering vocal fold contour by performing bilateral medialization of the inferior vocal fold affects phonation. This procedure could be performed in patients for whom pitch lowering is desirable, such as female-to-male transsexuals or male patients with mutational falsetto in whom intensive voice therapy was insufficient. Methods Aerodynamic, acoustic, and high-speed videokymographic data were collected for nine larynges at three subglottal pressure inputs for each of three conditions: normal; type IIIB thyroplasty; and combined type IIIB with modified bilateral type I thyroplasty intended to create a more rectangular glottal configuration. Each larynx served as its own control. Results Phonation threshold flow (p=0.005), phonation threshold power (p=0.031), and airflow varied across conditions with highest values for type IIIB thyroplasty and lowest for the combined procedure. Fundamental frequency was significantly different (p<0.001), decreasing by approximately 100 Hz from control to type IIIB trials, and then by approximately 15 Hz from IIIB to combined procedure trials. Vibratory amplitudes and intrafold phase difference were highest for type IIIB trials. Conclusions Addition of bilateral inferior medialization to type IIIB thyroplasty provided some further decrease in frequency, but mostly served to increase tension, reduce airflow, and produce a vibratory pattern which more closely mirrored control trials. Exploration of this combined procedure in patients may be warranted if not completely satisfied with the results from type IIIB thyroplasty alone. PMID:24241252

  1. A SCENARIO FOR THE FINE STRUCTURES OF SOLAR TYPE IIIb RADIO BURSTS BASED ON ELECTRON CYCLOTRON MASER EMISSION

    SciTech Connect

    Wang, C. B.

    2015-06-10

    A scenario based on electron cyclotron maser (ECM) emission is proposed for the fine structures of solar radio emission. It is suggested that under certain conditions modulation of the ratio between the plasma frequency and electron gyro frequency by ultra-low-frequency waves, which is a key parameter for excitation of ECM instability, may lead to the intermittent emission of radio waves. As an example, the explanation for the observed fine-structure components in the solar Type IIIb bursts is discussed in detail. Three primary issues of Type IIIb bursts are addressed: (1) the physical mechanism that results in intermittent emission elements that form a chain in the dynamic spectrum of Type IIIb bursts, (2) the cause of split pairs (or double stria) and triple stria, and (3) why only IIIb–III bursts are observed in the events of fundamental harmonic pair emission whereas IIIb–IIIb or III–IIIb bursts are very rarely observed.

  2. Isolated Limb Perfusion With Melphalan in Treating Patients With Stage IIIB-IV Melanoma or Sarcoma

    ClinicalTrials.gov

    2015-07-22

    Basal Cell Carcinoma of the Skin; Eccrine Carcinoma of the Skin; Recurrent Adult Soft Tissue Sarcoma; Recurrent Melanoma; Recurrent Skin Cancer; Squamous Cell Carcinoma of the Skin; Stage III Adult Soft Tissue Sarcoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Melanoma

  3. Migrant Grantees Directory: Title III-B Programs and Key Staff, Office of Economic Opportunity.

    ERIC Educational Resources Information Center

    National Migrant Information Clearinghouse, Austin, TX. Juarez-Lincoln Center.

    Eighty-eight Title III-B (Office of Economic Opportunity) grantees and contracting organizations are listed in this handbook for use by agencies working with migrant farm workers. The grantees and organizations are listed alphabetically by state. Mailing addresses and phone numbers, a listing of all key personnel as of August 1973, and the Board…

  4. Negative pressure wound therapy for Gustilo Anderson grade IIIb open tibial fractures

    PubMed Central

    Park, Chul Hyun; Shon, Oog Jin; Kim, Gi Beom

    2016-01-01

    Background: Traditionally, Gustilo Anderson grade IIIb open tibial fractures have been treated by initial wide wound debridement, stabilization of fracture with external fixation, and delayed wound closure. The purpose of this study is to evaluate the clinical and radiological results of staged treatment using negative pressure wound therapy (NPWT) for Gustilo Anderson grade IIIb open tibial fractures. Materials and Methods: 15 patients with Gustilo Anderson grade IIIb open tibial fractures, treated using staged protocol by a single surgeon between January 2007 and December 2011 were reviewed in this retrospective study. The clinical results were assessed using a Puno scoring system for severe open fractures of the tibia at the last followup. The range of motion (ROM) of the knee and ankle joints and postoperative complication were evaluated at the last followup. The radiographic results were assessed using time to bone union, coronal and sagittal angulations and a shortening at the last followup. Results: The mean score of Puno scoring system was 87.4 (range 67–94). The mean ROM of the knee and ankle joints was 121.3° (range 90°–130°) and 37.7° (range 15°–50°), respectively. Bone union developed in all patients and the mean time to union was 25.3 weeks (range 16–42 weeks). The mean coronal angulation was 2.1° (range 0–4°) and sagittal was 2.7° (range 1–4°). The mean shortening was 4.1 mm (range 0–8 mm). Three patients had partial flap necrosis and 1 patient had total flap necrosis. There was no superficial and deep wound infection. Conclusion: Staged treatment using NPWT decreased the risks of infection and requirement of flap surgeries in Gustilo Anderson grade IIIb open tibial fractures. Therefore, staged treatment using NPWT could be a useful treatment option for Gustilo Anderson grade IIIb open tibial fractures. PMID:27746498

  5. Results of a conservative treatment combining induction (neoadjuvant) and consolidation chemotherapy, hormonotherapy, and external and interstitial irradiation in 98 patients with locally advanced breast cancer (IIIA-IIIB)

    SciTech Connect

    Jacquillat, C.; Baillet, F.; Weil, M.; Auclerc, G.; Housset, M.; Auclerc, M.; Sellami, M.; Jindani, A.; Thill, L.; Soubrane, C.

    1988-05-15

    Ninety-eight patients with locally advanced breast cancer (Stage IIIA-IIIB) were entered into a pilot study combining intensive induction (neoadjuvant) chemotherapy (VTMFAP) with or without hormonochemotherapy, external and interstitial radiotherapy, and consolidation chemotherapy with or without hormonochemotherapy. Tumor regression over 50% was observed in 91% patients after chemotherapy, and complete clinical remission occurred in 100% patients after irradiation. The rate of local relapse is 13%. The 3-year disease-free survival is 62% and 3-year global survival is 77%. Initial chemotherapeutic tumor regression greater than 75% is the main predictive factor for disease-free survival.

  6. RADGEN: A radiation exchange factor generator for rod bundles

    SciTech Connect

    Rector, D.R.

    1987-10-01

    The RADGEN computer program has been developed at Pacific Northwest Laboratory (PNL) to generate input required for the thermal radiation models used in the COBRA-SFS (Spent Fuel Storage) computer program. The COBRA-SFS program uses radiation exchange factors to describe the net amount of energy transferred from each surface to every other surface in an enclosure. The RADGEN program generates radiation exchange factors for arrays of rods on a square or triangular pitch as well as open channel geometries. This report describes the input requirements for the RADGEN code, which may be executed in a batch or interactive mode, and outlines the solution procedure used to obtain the exchange factors. 4 refs., 25 figs., 13 tabs.

  7. Neuropathology in Mouse Models of Mucopolysaccharidosis Type I, IIIA and IIIB

    PubMed Central

    Wilkinson, Fiona L.; Holley, Rebecca J.; Langford-Smith, Kia J.; Badrinath, Soumya; Liao, Aiyin; Langford-Smith, Alex; Cooper, Jonathan D.; Jones, Simon A.; Wraith, J. Ed; Wynn, Rob F.; Merry, Catherine L. R.; Bigger, Brian W.

    2012-01-01

    Mucopolysaccharide diseases (MPS) are caused by deficiency of glycosaminoglycan (GAG) degrading enzymes, leading to GAG accumulation. Neurodegenerative MPS diseases exhibit cognitive decline, behavioural problems and shortened lifespan. We have characterised neuropathological changes in mouse models of MPSI, IIIA and IIIB to provide a better understanding of these events. Wild-type (WT), MPSI, IIIA and IIIB mouse brains were analysed at 4 and 9 months of age. Quantitative immunohistochemistry showed significantly increased lysosomal compartment, GM2 ganglioside storage, neuroinflammation, decreased and mislocalised synaptic vesicle associated membrane protein, (VAMP2), and decreased post-synaptic protein, Homer-1, in layers II/III-VI of the primary motor, somatosensory and parietal cortex. Total heparan sulphate (HS), was significantly elevated, and abnormally N-, 6-O and 2-O sulphated compared to WT, potentially altering HS-dependent cellular functions. Neuroinflammation was confirmed by significantly increased MCP-1, MIP-1α, IL-1α, using cytometric bead arrays. An overall genotype effect was seen in all parameters tested except for synaptophysin staining, neuronal cell number and cortical thickness which were not significantly different from WT. MPSIIIA and IIIB showed significantly more pronounced pathology than MPSI in lysosomal storage, astrocytosis, microgliosis and the percentage of 2-O sulphation of HS. We also observed significant time progression of all genotypes from 4–9 months in lysosomal storage, astrocytosis, microgliosis and synaptic disorganisation but not GM2 gangliosidosis. Individual genotype*time differences were disparate, with significant progression from 4 to 9 months only seen for MPSIIIB with lysosomal storage, MPSI with astrocytocis and MPSIIIA with microgliosis as well as neuronal loss. Transmission electron microscopy of MPS brains revealed dystrophic axons, axonal storage, and extensive lipid and lysosomal storage. These data lend

  8. Mucopolysaccharidosis IIIB confers enhanced neonatal intracranial transduction by AAV8 but not by 5, 9 or rh10

    PubMed Central

    Gilkes, J A; Bloom, M D; Heldermon, C D

    2016-01-01

    Sanfilippo syndrome type B (mucopolysaccharidosis IIIB, MPS IIIB) is a lysosomal storage disease resulting from deficiency of N-acetyl-glucosaminidase (NAGLU) activity. To determine the possible therapeutic utility of recombinant adeno-associated virus (rAAV) in early gene therapy-based interventions, we performed a comprehensive assessment of transduction and biodistribution profiles of four central nervous system (CNS) administered rAAV serotypes, -5, -8, -9 and -rh10. To simulate optimal earliest treatment of the disease, each rAAV serotype was injected into the CNS of neonatal MPS IIIB and control animals. We observed marked differences in biodistribution and transduction profiles between the serotypes and this differed in MPS IIIB compared with healthy control mice. Overall, in control mice, all serotypes performed comparably, although some differences were observed in certain focal areas. In MPS IIIB mice, AAV8 was more efficient than AAV5, -9 and -rh10 for gene delivery to most structures analyzed, including the cerebral cortex, hippocampus and thalamus. Noteworthy, the pattern of biodistribution within the CNS varied by serotype and genotype. Interestingly, AAV8 also produced the highest green fluorescent protein intensity levels compared with any other serotype and demonstrated improved transduction in NAGLU compared with control brains. Importantly, we also show leakage of AAV8, -9 and -rh10, but not AAV5, from CNS parenchyma to systemic organs. Overall, our data suggest that AAV8 represents the best therapeutic gene transfer vector for early intervention in MPS IIIB. PMID:26674264

  9. Developing the Next Generation Shell Buckling Design Factors and Technologies

    NASA Technical Reports Server (NTRS)

    Hilburger, Mark W.

    2012-01-01

    NASA s Shell Buckling Knockdown Factor (SBKF) Project was established in the spring of 2007 by the NASA Engineering and Safety Center (NESC) in collaboration with the Constellation Program and Exploration Systems Mission Directorate. The SBKF project has the current goal of developing less-conservative, robust shell buckling design factors (a.k.a. knockdown factors) and design and analysis technologies for light-weight stiffened metallic launch vehicle (LV) structures. Preliminary design studies indicate that implementation of these new knockdown factors can enable significant reductions in mass and mass-growth in these vehicles and can help mitigate some of NASA s LV development and performance risks. In particular, it is expected that the results from this project will help reduce the reliance on testing, provide high-fidelity estimates of structural performance, reliability, robustness, and enable increased payload capability. The SBKF project objectives and approach used to develop and validate new design technologies are presented, and provide a glimpse into the future of design of the next generation of buckling-critical launch vehicle structures.

  10. Radiation therapy generates platelet-activating factor agonists

    PubMed Central

    Sahu, Ravi P.; Harrison, Kathleen A.; Weyerbacher, Jonathan; Murphy, Robert C.; Konger, Raymond L.; Garrett, Joy Elizabeth; Chin-Sinex, Helen Jan; Johnston, Michael Edward; Dynlacht, Joseph R.; Mendonca, Marc; McMullen, Kevin; Li, Gengxin; Spandau, Dan F.; Travers, Jeffrey B.

    2016-01-01

    Pro-oxidative stressors can suppress host immunity due to their ability to generate oxidized lipid agonists of the platelet-activating factor-receptor (PAF-R). As radiation therapy also induces reactive oxygen species, the present studies were designed to define whether ionizing radiation could generate PAF-R agonists and if these lipids could subvert host immunity. We demonstrate that radiation exposure of multiple tumor cell lines in-vitro, tumors in-vivo, and human subjects undergoing radiation therapy for skin tumors all generate PAF-R agonists. Structural characterization of radiation-induced PAF-R agonistic activity revealed PAF and multiple oxidized glycerophosphocholines that are produced non-enzymatically. In a murine melanoma tumor model, irradiation of one tumor augmented the growth of the other (non-treated) tumor in a PAF-R-dependent process blocked by a cyclooxygenase-2 inhibitor. These results indicate a novel pathway by which PAF-R agonists produced as a byproduct of radiation therapy could result in tumor treatment failure, and offer important insights into potential therapeutic strategies that could improve the overall antitumor effectiveness of radiation therapy regimens. PMID:26959112

  11. Radiation therapy generates platelet-activating factor agonists.

    PubMed

    Sahu, Ravi P; Harrison, Kathleen A; Weyerbacher, Jonathan; Murphy, Robert C; Konger, Raymond L; Garrett, Joy Elizabeth; Chin-Sinex, Helen Jan; Johnston, Michael Edward; Dynlacht, Joseph R; Mendonca, Marc; McMullen, Kevin; Li, Gengxin; Spandau, Dan F; Travers, Jeffrey B

    2016-04-12

    Pro-oxidative stressors can suppress host immunity due to their ability to generate oxidized lipid agonists of the platelet-activating factor-receptor (PAF-R). As radiation therapy also induces reactive oxygen species, the present studies were designed to define whether ionizing radiation could generate PAF-R agonists and if these lipids could subvert host immunity. We demonstrate that radiation exposure of multiple tumor cell lines in-vitro, tumors in-vivo, and human subjects undergoing radiation therapy for skin tumors all generate PAF-R agonists. Structural characterization of radiation-induced PAF-R agonistic activity revealed PAF and multiple oxidized glycerophosphocholines that are produced non-enzymatically. In a murine melanoma tumor model, irradiation of one tumor augmented the growth of the other (non-treated) tumor in a PAF-R-dependent process blocked by a cyclooxygenase-2 inhibitor. These results indicate a novel pathway by which PAF-R agonists produced as a byproduct of radiation therapy could result in tumor treatment failure, and offer important insights into potential therapeutic strategies that could improve the overall antitumor effectiveness of radiation therapy regimens. PMID:26959112

  12. Link community detection using generative model and nonnegative matrix factorization.

    PubMed

    He, Dongxiao; Jin, Di; Baquero, Carlos; Liu, Dayou

    2014-01-01

    Discovery of communities in complex networks is a fundamental data analysis problem with applications in various domains. While most of the existing approaches have focused on discovering communities of nodes, recent studies have shown the advantages and uses of link community discovery in networks. Generative models provide a promising class of techniques for the identification of modular structures in networks, but most generative models mainly focus on the detection of node communities rather than link communities. In this work, we propose a generative model, which is based on the importance of each node when forming links in each community, to describe the structure of link communities. We proceed to fit the model parameters by taking it as an optimization problem, and solve it using nonnegative matrix factorization. Thereafter, in order to automatically determine the number of communities, we extend the above method by introducing a strategy of iterative bipartition. This extended method not only finds the number of communities all by itself, but also obtains high efficiency, and thus it is more suitable to deal with large and unexplored real networks. We test this approach on both synthetic benchmarks and real-world networks including an application on a large biological network, and compare it with two highly related methods. Results demonstrate the superior performance of our approach over competing methods for the detection of link communities.

  13. Implant Materials Generate Different Peri-implant Inflammatory Factors

    PubMed Central

    Olivares-Navarrete, Rene; Hyzy, Sharon L.; Slosar, Paul J.; Schneider, Jennifer M.; Schwartz, Zvi

    2015-01-01

    Study Design. An in vitro study examining factors produced by human mesenchymal stem cells on spine implant materials. Objective. The aim of this study was to examine whether the inflammatory microenvironment generated by cells on titanium-aluminum-vanadium (Ti-alloy, TiAlV) surfaces is affected by surface microtexture and whether it differs from that generated on poly-ether-ether-ketone (PEEK). Summary of Background Data. Histologically, implants fabricated from PEEK have a fibrous connective tissue surface interface whereas Ti-alloy implants demonstrate close approximation with surrounding bone. Ti-alloy surfaces with complex micron/submicron scale roughness promote osteoblastic differentiation and foster a specific cellular environment that favors bone formation whereas PEEK favors fibrous tissue formation. Methods. Human mesenchymal stem cells were cultured on tissue culture polystyrene, PEEK, smooth TiAlV, or macro-/micro-/nano-textured rough TiAlV (mmnTiAlV) disks. Osteoblastic differentiation and secreted inflammatory interleukins were assessed after 7 days. Fold changes in mRNAs for inflammation, necrosis, DNA damage, or apoptosis with respect to tissue culture polystyrene were measured by low-density polymerase chain reaction array. Data were analyzed by analysis of variance, followed by Bonferroni's correction of Student's t-test. Results. Cells on PEEK upregulated mRNAs for chemokine ligand-2, interleukin (IL) 1β, IL6, IL8, and tumor necrosis factor. Cells grown on the mmnTiAlV had an 8-fold reduction in mRNAs for toll-like receptor-4. Cells grown on mmnTiAlV had reduced levels of proinflammatory interleukins. Cells on PEEK had higher mRNAs for factors strongly associated with cell death/apoptosis, whereas cells on mmnTiAlV exhibited reduced cytokine factor levels. All results were significant (P < 0.05). Conclusion. These results suggest that fibrous tissue around PEEK implants may be due to several factors: reduced osteoblastic differentiation of

  14. Electrophysiological and Histological Characterization of Rod-Cone Retinal Degeneration and Microglia Activation in a Mouse Model of Mucopolysaccharidosis Type IIIB

    PubMed Central

    Tse, Dennis Y.; Lotfi, Parisa; Simons, David L.; Sardiello, Marco; Wu, Samuel M.

    2015-01-01

    Sanfilippo syndrome Type B or Mucopolysaccharidosis IIIB (MPS IIIB) is a neurodegenerative autosomal recessive lysosomal storage disorder in which patients suffer severe vision loss from associated retinopathy. Here we sought to study the underlying retinal functional and morphological changes associated with MPS IIIB disease progression using the established model of MPS IIIB, the B6.129S6-Naglu(tm1Efn)/J mouse line. Electroretinogram (ERG) was recorded from MPS IIIB and wild-type (WT) mice at the age of 28 and 46 weeks, and retinal tissues were subsequently collected for immunohistochemistry analysis. At the 28th week, rod a- and b-wave amplitudes were significantly diminished in MPS IIIB compared to WT mice. The cone a- and b-waves of MPS IIIB mice were not significantly different from those of the control at the 28th week but were significantly diminished at the 46th week, when MPS IIIB mice showed a major loss of rods and rod bipolar cells in both central and peripheral regions and a minor loss of cones in the periphery. Activation of microglia and neovascularization were also detected in the MPS IIIB retina. The new findings that cones and rod bipolar cells also undergo degeneration, and that retinal microglia are activated, will inform future development of therapeutic strategies. PMID:26607664

  15. The Next Generation of Transcription Factor Binding Site Prediction

    PubMed Central

    Mathelier, Anthony; Wasserman, Wyeth W.

    2013-01-01

    Finding where transcription factors (TFs) bind to the DNA is of key importance to decipher gene regulation at a transcriptional level. Classically, computational prediction of TF binding sites (TFBSs) is based on basic position weight matrices (PWMs) which quantitatively score binding motifs based on the observed nucleotide patterns in a set of TFBSs for the corresponding TF. Such models make the strong assumption that each nucleotide participates independently in the corresponding DNA-protein interaction and do not account for flexible length motifs. We introduce transcription factor flexible models (TFFMs) to represent TF binding properties. Based on hidden Markov models, TFFMs are flexible, and can model both position interdependence within TFBSs and variable length motifs within a single dedicated framework. The availability of thousands of experimentally validated DNA-TF interaction sequences from ChIP-seq allows for the generation of models that perform as well as PWMs for stereotypical TFs and can improve performance for TFs with flexible binding characteristics. We present a new graphical representation of the motifs that convey properties of position interdependence. TFFMs have been assessed on ChIP-seq data sets coming from the ENCODE project, revealing that they can perform better than both PWMs and the dinucleotide weight matrix extension in discriminating ChIP-seq from background sequences. Under the assumption that ChIP-seq signal values are correlated with the affinity of the TF-DNA binding, we find that TFFM scores correlate with ChIP-seq peak signals. Moreover, using available TF-DNA affinity measurements for the Max TF, we demonstrate that TFFMs constructed from ChIP-seq data correlate with published experimentally measured DNA-binding affinities. Finally, TFFMs allow for the straightforward computation of an integrated TF occupancy score across a sequence. These results demonstrate the capacity of TFFMs to accurately model DNA

  16. Clinical significance of aberrant mammalian target of rapamycin expression in stage IIIB colon cancer

    PubMed Central

    WEN, MEILING; LI, BAOXIU; CAO, XIAOFEI; WENG, CHENGYIN; WU, YONG; FANG, XISHENG; ZHANG, XIAOSHI; LIU, GUOLONG

    2014-01-01

    The aim of the present study was to investigate the significance of aberrant expression of mammalian target of rapamycin (mTOR) and the activated form of mTOR kinase, phosphorylated mTOR (pmTOR), in human stage IIIB colon cancer. The expression of mTOR and pmTOR was detected by immunohistochemistry in the tumor tissue of stage IIIB colon cancer patients. The association between the expression of mTOR, pmTOR and clinicopathological parameters of patients was analyzed. The positive expression of mTOR and pmTOR was observed to be higher in 75.5% (80/106) and 76.4% (81/106) of the 106 colon cancer specimens, compared with the adjacent normal tissues. The high level of pmTOR expression was found to be significantly higher in the invasive tumor front cells and resulted in a higher risk of mortality. The results suggested that mTOR and pmTOR may be promising clinical markers and present novel molecular targets for designing novel therapeutic strategies to treat this malignancy. PMID:25120661

  17. High duty factor plasma generator for CERN's Superconducting Proton Linac.

    PubMed

    Lettry, J; Kronberger, M; Scrivens, R; Chaudet, E; Faircloth, D; Favre, G; Geisser, J-M; Küchler, D; Mathot, S; Midttun, O; Paoluzzi, M; Schmitzer, C; Steyaert, D

    2010-02-01

    CERN's Linac4 is a 160 MeV linear accelerator currently under construction. It will inject negatively charged hydrogen ions into CERN's PS-Booster. Its ion source is a noncesiated rf driven H(-) volume source directly inspired from the one of DESY and is aimed to deliver pulses of 80 mA of H(-) during 0.4 ms at a 2 Hz repetition rate. The Superconducting Proton Linac (SPL) project is part of the luminosity upgrade of the Large Hadron Collider. It consists of an extension of Linac4 up to 5 GeV and is foreseen to deliver protons to a future 50 GeV synchrotron (PS2). For the SPL high power option (HP-SPL), the ion source would deliver pulses of 80 mA of H(-) during 1.2 ms and operate at a 50 Hz repetition rate. This significant upgrade motivates the design of the new water cooled plasma generator presented in this paper. Its engineering is based on the results of a finite element thermal study of the Linac4 H(-) plasma generator that identified critical components and thermal barriers. A cooling system is proposed which achieves the required heat dissipation and maintains the original functionality. Materials with higher thermal conductivity are selected and, wherever possible, thermal barriers resulting from low pressure contacts are removed by brazing metals on insulators. The AlN plasma chamber cooling circuit is inspired from the approach chosen for the cesiated high duty factor rf H(-) source operating at SNS. PMID:20192392

  18. High duty factor plasma generator for CERN's Superconducting Proton Linac.

    PubMed

    Lettry, J; Kronberger, M; Scrivens, R; Chaudet, E; Faircloth, D; Favre, G; Geisser, J-M; Küchler, D; Mathot, S; Midttun, O; Paoluzzi, M; Schmitzer, C; Steyaert, D

    2010-02-01

    CERN's Linac4 is a 160 MeV linear accelerator currently under construction. It will inject negatively charged hydrogen ions into CERN's PS-Booster. Its ion source is a noncesiated rf driven H(-) volume source directly inspired from the one of DESY and is aimed to deliver pulses of 80 mA of H(-) during 0.4 ms at a 2 Hz repetition rate. The Superconducting Proton Linac (SPL) project is part of the luminosity upgrade of the Large Hadron Collider. It consists of an extension of Linac4 up to 5 GeV and is foreseen to deliver protons to a future 50 GeV synchrotron (PS2). For the SPL high power option (HP-SPL), the ion source would deliver pulses of 80 mA of H(-) during 1.2 ms and operate at a 50 Hz repetition rate. This significant upgrade motivates the design of the new water cooled plasma generator presented in this paper. Its engineering is based on the results of a finite element thermal study of the Linac4 H(-) plasma generator that identified critical components and thermal barriers. A cooling system is proposed which achieves the required heat dissipation and maintains the original functionality. Materials with higher thermal conductivity are selected and, wherever possible, thermal barriers resulting from low pressure contacts are removed by brazing metals on insulators. The AlN plasma chamber cooling circuit is inspired from the approach chosen for the cesiated high duty factor rf H(-) source operating at SNS.

  19. FGFR2IIIb-MAPK Activity Is Required for Epithelial Cell Fate Decision in the Lower Müllerian Duct.

    PubMed

    Terakawa, Jumpei; Rocchi, Altea; Serna, Vanida A; Bottinger, Erwin P; Graff, Jonathan M; Kurita, Takeshi

    2016-07-01

    Cell fate of lower Müllerian duct epithelium (MDE), to become uterine or vaginal epithelium, is determined by the absence or presence of ΔNp63 expression, respectively. Previously, we showed that SMAD4 and runt-related transcription factor 1 (RUNX1) were independently required for MDE to express ΔNp63. Here, we report that vaginal mesenchyme directs vaginal epithelial cell fate in MDE through paracrine activation of fibroblast growth factor (FGF) receptor-MAPK pathway. In the developing reproductive tract, FGF7 and FGF10 were enriched in vaginal mesenchyme, whereas FGF receptor 2IIIb was expressed in epithelia of both the uterus and vagina. When Fgfr2 was inactivated, vaginal MDE underwent uterine cell fate, and this differentiation defect was corrected by activation of MEK-ERK pathway. In vitro, FGF10 in combination with bone morphogenetic protein 4 and activin A (ActA) was sufficient to induce ΔNp63 in MDE, and ActA was essential for induction of RUNX1 through SMAD-independent pathways. Accordingly, inhibition of type 1 receptors for activin in neonatal mice induced uterine differentiation in vaginal epithelium by down-regulating RUNX1, whereas conditional deletion of Smad2 and Smad3 had no effect on vaginal epithelial differentiation. In conclusion, vaginal epithelial cell fate in MDE is induced by FGF7/10-MAPK, bone morphogenetic protein 4-SMAD, and ActA-RUNX1 pathway activities, and the disruption in any one of these pathways results in conversion from vaginal to uterine epithelial cell fate. PMID:27164167

  20. Generation and characterization of transgenic mice expressing cobra venom factor.

    PubMed

    Andrä, Jörg; Halter, Roman; Kock, Michael A; Niemann, Heiner; Vogel, Carl-Wilhelm; Paul, Dieter

    2002-10-01

    Cobra venom factor (CVF), the anticomplementary protein in cobra venom, activates the alternative complement pathway, eventually leading to complement consumption. Here, we describe the development of a transgenic mouse model for CVF. We generated a DNA construct containing the full-length cDNA for single-chain pre-pro-CVF. Expression of CVF was controlled by the alpha(1)-antitrypsin promoter to achieve liver-specific expression. Linearized DNA was microinjected into murine ovary cells (strain CD(2)F(1) (BALB/cxDBA/2J)) and the newborn mice were analyzed for stable integration of CVF DNA. After establishing the transgene, mice were propagated in a BALB/c background. The CVF mRNA was detected in the liver and, in some animals, in the kidney. CVF protein was detected in small amounts in the serum. Serum complement hemolytic activity in CVF-transgenic mice was virtually absent. The concentration of plasma C3 was significantly reduced. The CVF-transgenic animals show no unusual phenotype. They provide an animal model to study the effect of long-term complement depletion by continued activation, as well as the role of complement in host immune response and pathogenesis of disease. PMID:12220893

  1. Cue Set Stimulation as a Factor in Human Response Generation.

    ERIC Educational Resources Information Center

    Petelle, John L.

    The hypotheses that there will be a significant difference (1) in the number of responses generated according to economic issues, (2) in the number of responses generated according to social issues, (3) in the number of responses generated between the category of economic issues and the category of social issues, (4) in cue ranking by response…

  2. Ab initio and DFT studies on vibrational spectra of some halides of group IIIB elements

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Zhao, Jianying; Tang, Guodong; Zhu, Longgen

    2005-11-01

    The vibrational spectra of some group IIIB elements halides MX 3 and their dimmers, M 2X 6 (M = Sc(III), Y(III), La(III); X = F, Cl, Br, I), have been systematically investigated by ab initio restricted Hartree-Fock (RHF) and density functional B3LYP methods with LanL2DZ and SDD basis sets. The optimized geometries and calculated vibrational frequencies are evaluated via comparison with experimental values. The vibrational frequencies, calculated by two methods with different basis sets, are compared to each other. The effect of the methods and the basis sets used on the calculated vibrational frequencies are discussed. Some vibrational frequencies of these complexes are also predicted.

  3. Coenzyme A Binding to the Aminoglycoside Acetyltransferase (3)-IIIb Increases Conformational Sampling of Antibiotic Binding Site

    SciTech Connect

    Hu, Xiaohu; Norris, Adrianne; Baudry, Jerome Y; Serpersu, Engin H

    2011-01-01

    NMR spectroscopy experiments and molecular dynamics simulations were performed to describe the dynamic properties of the aminoglycoside acetyltransferase (3)-IIIb (AAC) in its apo and coenzyme A (CoASH) bound forms. The {sup 15}N-{sup 1}H HSQC spectra indicate a partial structural change and coupling of the CoASH binding site with another region in the protein upon the CoASH titration into the apo enzyme. Molecular dynamics simulations indicate a significant structural and dynamic variation of the long loop in the antibiotic binding domain in the form of a relatively slow (250 ns), concerted opening motion in the CoASH enzyme complex and that binding of the CoASH increases the structural flexibility of the loop, leading to an interchange between several similar equally populated conformations.

  4. A qualitative study of recovery from type III-B and III-C tibial fractures.

    PubMed

    Shauver, Melissa S; Aravind, Maya S; Chung, Kevin C

    2011-01-01

    The literature has shown that long-term outcomes for both below-knee amputation and reconstruction after type III-B and III-C tibial fracture are poor. Yet, patients often report satisfaction with their treatment and outcomes. The aim of this study was to explore the relationship between patient outcomes and satisfaction after open tibial fractures via qualitative methodology. Twenty patients who were treated for open tibial fractures at one institution were selected using purposeful sampling and interviewed in-person in a semi-structured manner. Data were analyzed using grounded theory methodology. Despite reporting marked physical and psychosocial deficits, participants relayed high satisfaction. We hypothesize that the use of adaptive coping techniques successfully reduces stress, which leads to an increase in coping self-efficacy that results in the further use of adaptive coping strategies, culminating in personal growth. This stress reduction and personal growth leads to satisfaction despite poor functional and emotional outcomes.

  5. On dynamic and elastic stability of group IIIB metal carbides: Ab-initio calculations

    NASA Astrophysics Data System (ADS)

    Sahoo, B. D.; Mukherjee, D.; Joshi, K. D.; Gupta, Satish C.

    2012-06-01

    The elastic and dynamic stabilities of IIIB metal carbides in NaCl (B1 phase) type fcc structure have been investigated at zero pressure by first-principles calculations using the plane-wave pseudopotential method. The analysis of elastic moduli and phonon dispersion relations in ScC and YC suggest that the B1 phase is stable both elastically as well as dynamically at zero pressure. In contrast, for LaC, we find that the shear elastic modulus C' (=(C11-C12)/2) is negative at zero pressure and also the phonon frequencies in various directions of the Brillouin zone are imaginary, indicative of elastic as well as dynamic instability of B1 phase at zero pressure in this compound.

  6. 77 FR 39388 - Removal of Category IIIa, IIIb, and IIIc Definitions; Confirmation of Effective Date and Response...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ... confirms the effective date of the direct final rule published on February 16, 2012 (77 FR 9163), and..., entitled ``Removal of Category IIIa, IIIb, and IIIc Definitions'' (77 FR 9163). The direct final rule..._policies/ or 3. Access the Government Printing Office's Web page at...

  7. Metabolome profiling to understand the defense response to sugar beet (Beta vulgaris) to Rhizoctonia solani AG 2-2 IIIB

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rhizoctonia crown and root rot, caused by Rhizoctonia solani Kühn AG 2-2 IIIB, is an important disease of sugar beet (Beta vulgaris L.). The molecular processes that mediate sugar beet resistance to R. solani are largely unknown and identifying the metabolites associated with R. solani infection ma...

  8. Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2016-02-08

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  9. Harmonic relation of type IIIb-III solar radio bursts in 6.25, 12.5, and 25.0 MHz octaves

    NASA Astrophysics Data System (ADS)

    Abranin, E. P.; Bazelian, L. L.; Tsybko, Ia. G.

    1984-04-01

    This study of type IIIb-III events strongly supports their interpretation as fundamental-harmonic burst pairs. Type IIIb chains and the related type III bursts drift from 12.5 to 6.25 MHz and from 25.0 to 12.5 MHz, respectively, during similar time intervals of 11.1 and 11.0 s, on the average. This harmonic similarity is emphasized by the fact that the drift times of type IIIb chains across the upper octave are significantly less than those of type III bursts in the lower octave, the values being around 6 and 19 s.

  10. Literature Review: Factors Affecting the Development of Generation X and Millennials. Societal Factors Affecting Education.

    ERIC Educational Resources Information Center

    Denham, Thomas J.; adbow, Nancy

    Generation X, or "Xers," refers to those born in the United States between 1960 and 1980 and Generation Y, also known as "Millennials," refers to those born between 1980 and 2000. An examination of these two generations is important to educators as the new generation of Millennials begins to access higher education. A large and growing body of…

  11. Space factor of "excess" heat generation in the Earth and planetary interiors. Article 5. Possible heat generating particles

    NASA Astrophysics Data System (ADS)

    Makarenko, O. M.

    Besides radiogenic energy, the "extra" energy source occurs in the Earth interior. This source is of cosmic origin and modulated by position and direction of the Solar system motion in the Galaxy. Dark matter from the galactic disk might be a factor leading to the energy release. Candidate heat generating particles are: particles of the fourth generation, axions, magnetic monopoles, small black holes, and some others.

  12. Combination Chemotherapy and Peripheral Blood Stem Cell Transplant Followed By Aldesleukin and Sargramostim in Treating Patients With Inflammatory Stage IIIB or Metastatic Stage IV Breast Cancer

    ClinicalTrials.gov

    2011-07-08

    Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; Inflammatory Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer

  13. Exploring First Generation African American Graduate Students: Motivating Factors for Pursuing a Doctoral Degree

    ERIC Educational Resources Information Center

    Adams, Stephanie G.

    2011-01-01

    The purpose for conducting the study was to examine the factors that motivate African-American first-generation students to pursue doctoral education at a four-year public university. There has been little research on the influence academic or nonacademic factors have on first-generation graduate student motivation. Similarly, little research…

  14. Factors associated with the satisfaction of millennial generation dental residents.

    PubMed

    Lam, Hwai-Tai C; O'Toole, Terry G; Arola, Patricia E; Kashner, T Michael; Chang, Barbara K

    2012-11-01

    Data from the 2010 Learners' Perceptions Survey (LPS) administered through the Office of Academic Affiliations, Department of Veterans Affairs (VA) were analyzed to identify factors associated with dental residents' satisfaction with the VA as a clinical training environment. Satisfaction scores were linked to clinic workloads, dental procedure complexity levels, staffing patterns, and facility infrastructure data to explore conditions that may improve residents' satisfaction. Findings supported the construct validity of the LPS survey data and underscored the importance of maintaining optimal ratios of attending dentists, dental assistants, and administrative staff to residents so that each trainee will have opportunities to perform an adequate level of dental workload. As programs strive to improve the quality of graduate dental education, findings from this study are vital for setting curriculum design guidelines and for providing infrastructure support for dental resident education. PMID:23144476

  15. Limestone: high-throughput candidate phenotype generation via tensor factorization.

    PubMed

    Ho, Joyce C; Ghosh, Joydeep; Steinhubl, Steve R; Stewart, Walter F; Denny, Joshua C; Malin, Bradley A; Sun, Jimeng

    2014-12-01

    The rapidly increasing availability of electronic health records (EHRs) from multiple heterogeneous sources has spearheaded the adoption of data-driven approaches for improved clinical research, decision making, prognosis, and patient management. Unfortunately, EHR data do not always directly and reliably map to medical concepts that clinical researchers need or use. Some recent studies have focused on EHR-derived phenotyping, which aims at mapping the EHR data to specific medical concepts; however, most of these approaches require labor intensive supervision from experienced clinical professionals. Furthermore, existing approaches are often disease-centric and specialized to the idiosyncrasies of the information technology and/or business practices of a single healthcare organization. In this paper, we propose Limestone, a nonnegative tensor factorization method to derive phenotype candidates with virtually no human supervision. Limestone represents the data source interactions naturally using tensors (a generalization of matrices). In particular, we investigate the interaction of diagnoses and medications among patients. The resulting tensor factors are reported as phenotype candidates that automatically reveal patient clusters on specific diagnoses and medications. Using the proposed method, multiple phenotypes can be identified simultaneously from data. We demonstrate the capability of Limestone on a cohort of 31,815 patient records from the Geisinger Health System. The dataset spans 7years of longitudinal patient records and was initially constructed for a heart failure onset prediction study. Our experiments demonstrate the robustness, stability, and the conciseness of Limestone-derived phenotypes. Our results show that using only 40 phenotypes, we can outperform the original 640 features (169 diagnosis categories and 471 medication types) to achieve an area under the receiver operator characteristic curve (AUC) of 0.720 (95% CI 0.715 to 0.725). Moreover, in

  16. A Review of Operational Water Consumption and Withdrawal Factors for Electricity Generating Technologies

    SciTech Connect

    Macknick, Jordan; Newmark, Robin; Heath, Garvin; Hallett, K. C.

    2011-03-01

    This report provides estimates of operational water withdrawal and water consumption factors for electricity generating technologies in the United States. Estimates of water factors were collected from published primary literature and were not modified except for unit conversions. The presented water factors may be useful in modeling and policy analyses where reliable power plant level data are not available.

  17. Factors that influence the generation of autobiographical memory conjunction errors.

    PubMed

    Devitt, Aleea L; Monk-Fromont, Edwin; Schacter, Daniel L; Addis, Donna Rose

    2016-01-01

    The constructive nature of memory is generally adaptive, allowing us to efficiently store, process and learn from life events, and simulate future scenarios to prepare ourselves for what may come. However, the cost of a flexibly constructive memory system is the occasional conjunction error, whereby the components of an event are authentic, but the combination of those components is false. Using a novel recombination paradigm, it was demonstrated that details from one autobiographical memory (AM) may be incorrectly incorporated into another, forming AM conjunction errors that elude typical reality monitoring checks. The factors that contribute to the creation of these conjunction errors were examined across two experiments. Conjunction errors were more likely to occur when the corresponding details were partially rather than fully recombined, likely due to increased plausibility and ease of simulation of partially recombined scenarios. Brief periods of imagination increased conjunction error rates, in line with the imagination inflation effect. Subjective ratings suggest that this inflation is due to similarity of phenomenological experience between conjunction and authentic memories, consistent with a source monitoring perspective. Moreover, objective scoring of memory content indicates that increased perceptual detail may be particularly important for the formation of AM conjunction errors.

  18. Historical and contemporary factors generate unique butterfly communities on islands.

    PubMed

    Vodă, Raluca; Dapporto, Leonardo; Dincă, Vlad; Shreeve, Tim G; Khaldi, Mourad; Barech, Ghania; Rebbas, Khellaf; Sammut, Paul; Scalercio, Stefano; Hebert, Paul D N; Vila, Roger

    2016-01-01

    The mechanisms shaping island biotas are not yet well understood mostly because of a lack of studies comparing eco-evolutionary fingerprints over entire taxonomic groups. Here, we linked community structure (richness, frequency and nestedness) and genetic differentiation (based on mitochondrial DNA) in order to compare insular butterfly communities occurring over a key intercontinental area in the Mediterranean (Italy-Sicily-Maghreb). We found that community characteristics and genetic structure were influenced by a combination of contemporary and historical factors, and among the latter, connection during the Pleistocene had an important impact. We showed that species can be divided into two groups with radically different properties: widespread taxa had high dispersal capacity, a nested pattern of occurrence, and displayed little genetic structure, while rare species were mainly characterized by low dispersal, high turnover and genetically differentiated populations. These results offer an unprecedented view of the distinctive butterfly communities and of the main processes determining them on each studied island and highlight the importance of assessing the phylogeographic value of populations for conservation. PMID:27353723

  19. Historical and contemporary factors generate unique butterfly communities on islands

    PubMed Central

    Vodă, Raluca; Dapporto, Leonardo; Dincă, Vlad; Shreeve, Tim G.; Khaldi, Mourad; Barech, Ghania; Rebbas, Khellaf; Sammut, Paul; Scalercio, Stefano; Hebert, Paul D. N.; Vila, Roger

    2016-01-01

    The mechanisms shaping island biotas are not yet well understood mostly because of a lack of studies comparing eco-evolutionary fingerprints over entire taxonomic groups. Here, we linked community structure (richness, frequency and nestedness) and genetic differentiation (based on mitochondrial DNA) in order to compare insular butterfly communities occurring over a key intercontinental area in the Mediterranean (Italy-Sicily-Maghreb). We found that community characteristics and genetic structure were influenced by a combination of contemporary and historical factors, and among the latter, connection during the Pleistocene had an important impact. We showed that species can be divided into two groups with radically different properties: widespread taxa had high dispersal capacity, a nested pattern of occurrence, and displayed little genetic structure, while rare species were mainly characterized by low dispersal, high turnover and genetically differentiated populations. These results offer an unprecedented view of the distinctive butterfly communities and of the main processes determining them on each studied island and highlight the importance of assessing the phylogeographic value of populations for conservation. PMID:27353723

  20. Historical and contemporary factors generate unique butterfly communities on islands

    NASA Astrophysics Data System (ADS)

    Vodă, Raluca; Dapporto, Leonardo; Dincă, Vlad; Shreeve, Tim G.; Khaldi, Mourad; Barech, Ghania; Rebbas, Khellaf; Sammut, Paul; Scalercio, Stefano; Hebert, Paul D. N.; Vila, Roger

    2016-06-01

    The mechanisms shaping island biotas are not yet well understood mostly because of a lack of studies comparing eco-evolutionary fingerprints over entire taxonomic groups. Here, we linked community structure (richness, frequency and nestedness) and genetic differentiation (based on mitochondrial DNA) in order to compare insular butterfly communities occurring over a key intercontinental area in the Mediterranean (Italy-Sicily-Maghreb). We found that community characteristics and genetic structure were influenced by a combination of contemporary and historical factors, and among the latter, connection during the Pleistocene had an important impact. We showed that species can be divided into two groups with radically different properties: widespread taxa had high dispersal capacity, a nested pattern of occurrence, and displayed little genetic structure, while rare species were mainly characterized by low dispersal, high turnover and genetically differentiated populations. These results offer an unprecedented view of the distinctive butterfly communities and of the main processes determining them on each studied island and highlight the importance of assessing the phylogeographic value of populations for conservation.

  1. Historical and contemporary factors generate unique butterfly communities on islands.

    PubMed

    Vodă, Raluca; Dapporto, Leonardo; Dincă, Vlad; Shreeve, Tim G; Khaldi, Mourad; Barech, Ghania; Rebbas, Khellaf; Sammut, Paul; Scalercio, Stefano; Hebert, Paul D N; Vila, Roger

    2016-06-29

    The mechanisms shaping island biotas are not yet well understood mostly because of a lack of studies comparing eco-evolutionary fingerprints over entire taxonomic groups. Here, we linked community structure (richness, frequency and nestedness) and genetic differentiation (based on mitochondrial DNA) in order to compare insular butterfly communities occurring over a key intercontinental area in the Mediterranean (Italy-Sicily-Maghreb). We found that community characteristics and genetic structure were influenced by a combination of contemporary and historical factors, and among the latter, connection during the Pleistocene had an important impact. We showed that species can be divided into two groups with radically different properties: widespread taxa had high dispersal capacity, a nested pattern of occurrence, and displayed little genetic structure, while rare species were mainly characterized by low dispersal, high turnover and genetically differentiated populations. These results offer an unprecedented view of the distinctive butterfly communities and of the main processes determining them on each studied island and highlight the importance of assessing the phylogeographic value of populations for conservation.

  2. Factors affecting waste generation: a study in a waste management program in Dhaka City, Bangladesh.

    PubMed

    Afroz, Rafia; Hanaki, Keisuke; Tudin, Rabaah

    2011-08-01

    Information on waste generation, socioeconomic characteristics, and willingness of the households to separate waste was obtained from interviews with 402 respondents in Dhaka city. Ordinary least square regression was used to determine the dominant factors that might influence the waste generation of the households. The results showed that the waste generation of the households in Dhaka city was significantly affected by household size, income, concern about the environment, and willingness to separate the waste. These factors are necessary to effectively improve waste management, growth and performance, as well as to reduce the environmental degradation of the household waste. PMID:21046234

  3. Effect of Sugar Beet Variety and Nonhost Plant on Rhizoctonia solani AG2-2IIIB Soil Inoculum Potential Measured in Soil DNA Extracts.

    PubMed

    Schulze, Sascha; Koch, Heinz-Josef; Märländer, Bernward; Varrelmann, Mark

    2016-09-01

    A direct soil DNA extraction method from soil samples (250 g) was applied for detection of the soilborne sugar-beet-infecting pathogen Rhizoctonia solani anastomosis group (AG) 2-2IIIB using a newly developed real-time polymerase chain reaction assay that showed specificity to AG2-2IIIB when tested against various R. solani AG. The assay showed a good relation between cycle threshold and amount of AG2-2IIIB sclerotia detected in three spiked field soils and was also able to detect the pathogen in naturally infested field soil samples. A field trial was conducted to quantify R. solani AG2-2IIIB soil inoculum potential (IP) before and after growing a susceptible and a resistant sugar beet variety as well as after subsequent growth of an expected nonhost winter rye. Plants of the susceptible sugar beet variety displayed a higher disease severity. A more than sixfold increase of the R. solani AG2-2IIIB soil IP was observed in contrast to the resistant variety that resulted in a constant IP. Growing winter rye significantly reduced soil IP to the initial level at sowing. Further research is required to better understand the interaction between disease occurrence and soil IP as well as the environmental influence on IP development.

  4. Effect of Sugar Beet Variety and Nonhost Plant on Rhizoctonia solani AG2-2IIIB Soil Inoculum Potential Measured in Soil DNA Extracts.

    PubMed

    Schulze, Sascha; Koch, Heinz-Josef; Märländer, Bernward; Varrelmann, Mark

    2016-09-01

    A direct soil DNA extraction method from soil samples (250 g) was applied for detection of the soilborne sugar-beet-infecting pathogen Rhizoctonia solani anastomosis group (AG) 2-2IIIB using a newly developed real-time polymerase chain reaction assay that showed specificity to AG2-2IIIB when tested against various R. solani AG. The assay showed a good relation between cycle threshold and amount of AG2-2IIIB sclerotia detected in three spiked field soils and was also able to detect the pathogen in naturally infested field soil samples. A field trial was conducted to quantify R. solani AG2-2IIIB soil inoculum potential (IP) before and after growing a susceptible and a resistant sugar beet variety as well as after subsequent growth of an expected nonhost winter rye. Plants of the susceptible sugar beet variety displayed a higher disease severity. A more than sixfold increase of the R. solani AG2-2IIIB soil IP was observed in contrast to the resistant variety that resulted in a constant IP. Growing winter rye significantly reduced soil IP to the initial level at sowing. Further research is required to better understand the interaction between disease occurrence and soil IP as well as the environmental influence on IP development. PMID:27143412

  5. Evolution of pesticide resistance: interactions between generation time and genetic, ecological, and operational factors.

    PubMed

    Rosenheim, J; Tabashnik, B E

    1990-08-01

    We used computer simulation modeling to clarify the relationship between generation time and the rate of evolution of pesticide resistance. We examined the influence of generation time under various assumptions about genetics, population dynamics and selection pressures. The simplest model demonstrated that the time required for resistance to evolve can be independent of generation time. However, interactions of generation time with genetic, biological and operational factors resulted in positive, negative, and U-shaped relationships between the number of generations per year and the time required for resistance to evolve. These results preclude any generalizations concerning the influence of generation time on resistance evolution. Some ability to predict the influence of generation time may still exist on a case-by-case basis if the context of the resistance episode can be specified.

  6. High-power optical millimeter-wave signal generation with tunable frequency multiplication factor

    NASA Astrophysics Data System (ADS)

    Han, Yi-shi; Zheng, Zhenyu; Luo, Zhixiao; Min, Zhixuan; Xu, Ou; Liu, Jie

    2015-01-01

    This work demonstrates a simple and novel scheme for millimeter-wave (MMW) signal generation using optical multi-sidebands (OMSB) modulation. In the proposed methods, several pairs of optical sidebands can be generated by employing parallel phase modulators driven by a low frequency radio frequency (RF) signal. The optical sidebands will beat at a photodetector (PD) to generate high frequency MMW signal with tunable frequency multiplication factor, such as frequency octupling, 12-tupling, 16-tupling and 18-tupling. Since no optical filters or DC bias are used, the MMW signal has the evident character of high-power output. A generalized analytic expression and simulation verification for generating the frequency multi-tupling MMW signal are developed. The influences caused by non-ideal factors are discussed in detail, and undesired power ratios versus non-ideal factors are plotted and analyzed.

  7. Europium-activated phosphors containing oxides of rare-earth and group-IIIB metals and method of making the same

    DOEpatents

    Comanzo, Holly Ann; Setlur, Anant Achyut; Srivastava, Alok Mani

    2006-04-04

    Europium-activated phosphors comprise oxides of at least a rare-earth metal selected from the group consisting of gadolinium, yttrium, lanthanum, and combinations thereof and at least a Group-IIIB metal selected from the group consisting of aluminum, gallium, indium, and combinations thereof. A method for making such phosphors comprises adding at least a halide of at least one of the selected Group-IIIB metals in a starting mixture. The method further comprises firing the starting mixture in an oxygen-containing atmosphere. The phosphors produced by such a method exhibit improved absorption in the UV wavelength range and improved quantum efficiency.

  8. Europium-activated phosphors containing oxides of rare-earth and group-IIIB metals and method of making the same

    DOEpatents

    Comanzo, Holly Ann; Setlur, Anant Achyut; Srivastava, Alok Mani; Manivannan, Venkatesan

    2004-07-13

    Europium-activated phosphors comprise oxides of at least a rare-earth metal selected from the group consisting of gadolinium, yttrium, lanthanum, and combinations thereof and at least a Group-IIIB metal selected from the group consisting of aluminum, gallium, indium, and combinations thereof. A method for making such phosphors comprises adding at least a halide of at least one of the selected Group-IIIB metals in a starting mixture. The method further comprises firing the starting mixture in an oxygen-containing atmosphere. The phosphors produced by such a method exhibit improved absorption in the UV wavelength range and improved quantum efficiency.

  9. Three-dimensional surface grid generation for calculation of thermal radiation shape factors

    NASA Technical Reports Server (NTRS)

    Aly, Hany M.

    1992-01-01

    A technique is described to generate three dimensional surface grids suitable for calculating shape factors for thermal radiative heat transfer. The surface under consideration is approximated by finite triangular elements generated in a special manner. The grid is generated by dividing the surface into a two dimensional array of nodes. Each node is defined by its coordinates. Each set of four adjacent nodes is used to construct two triangular elements. Each triangular element is characterized by the vector representation of its vertices. Vector algebra is used to calculate all desired geometric properties of grid elements. The properties are used to determine the shape factor between the element and an area element in space. The grid generation can be graphically displayed using any software with three dimensional features. DISSPLA was used to view the grids.

  10. Recurrent infections in partial complement factor I deficiency: evaluation of three generations of a Brazilian family

    PubMed Central

    Grumach, A S; Leitão, M F; Arruk, V G; Kirschfink, M; Condino-Neto, A

    2006-01-01

    We report here on the evaluation of a factor I-deficient Brazilian family (three generations, 39 members) with strong consanguinity. The complete factor I-deficient patients (n = 3) presented recurrent respiratory infections, skin infections and meningitis; one of them died after sepsis. They presented an impaired total haemolytic activity (CH50), low C3, low factor H and undetectable C3dg/C3d. Partial factor I deficiency was detected in 16 family members (normal low cut-off value was 25 µg/ml). Respiratory infections were the most common clinical occurrence among partial factor I-deficient relatives. Two of them were submitted to nephrectomy following recurrent urinary tract infections. An additional two heterozygous relatives presented with arthritis and rheumatic fever. Apparently, patients with partial factor I deficiency are also at higher risk for recurrent infections. Vaccination against capsulated bacteria and the eventual use of prophylactic antibiotics should be considered individually in this patient group. PMID:16412054

  11. Comparison of Retention Factors between First-Generation and Second- and Third-Generation College Students and Development of the Likelihood of Success Model

    ERIC Educational Resources Information Center

    Williams, Gerri Brown

    2009-01-01

    The purpose of this study was to compare the retention factors between first-generation college students and second- and third-generation college students in the postsecondary educational setting. This study examined the differences in the preselected retention factors: faculty-student interaction, college mentor, academic support, residential…

  12. Generation of Lactococcus lactis capable of coexpressing epidermal growth factor and trefoil factor to enhance in vitro wound healing.

    PubMed

    Huynh, Evanna; Li, Julang

    2015-06-01

    Epidermal growth factor (EGF) and trefoil factor 3 (TFF3) are peptides that actively support the restitution and repair of mucosal epithelial barriers. Previous studies have shown that TFF3 enhanced EGF effect in wound healing, suggesting that the combined application of the two factors may be advantageous in clinical tissue repair. Expression of multiple proteins in a single host is a desirable approach in a biotechnological process, allowing to reduce cost and increase production efficiency. The aim of the present study was to study the feasibility of coexpressing EGF and TFF3 in food grade bacteria, Lactococcus lactis (L. lactis). Using an expression construct allowing simultaneous translation of two separate recombinant peptides, we generated a L. lactis that coexpressed and secreted EGF and TFF3 dually (LL-ET). Western blot analysis revealed that LL-ET secreted 45-54 % more total recombinant peptides (EGF+TFF3) per flask fermentation and 21-37 % more total recombinant proteins in bioreactor fermentation compared to their single factor expressing L. lactis counterparts (LL-EGF and LL-TFF3, respectively). The resulted recombinant EGF and TFF3 showed enhancement in wound healing activity in vitro. Our data suggest that the dual expression and secretion of EGF and TFF3 by L. lactis effectively accelerated cell migration, demonstrating potential future oral application of L. lactis fermentation product containing dual factors or a cocktail of factors to potentially treat intestinal damage and inflammation.

  13. Investigation of M2 factor influence for paraxial computer generated hologram reconstruction using a statistical method

    NASA Astrophysics Data System (ADS)

    Flury, M.; Gérard, P.; Takakura, Y.; Twardworski, P.; Fontaine, J.

    2005-04-01

    In this paper, we study the influence of the M2 quality factor of an incident beam on the reconstruction performance of a computer generated hologram (CGH). We use a statistical method to analyze the evolution of different quality criteria such as diffraction efficiency, root mean square error, illumination uniformity or correlation coefficient calculated in the numerical reconstruction versus the increasing M2 quality factor. The simulation results show us that this factor must always be taken into account in the CGH design when the M2 value is bigger than 2.

  14. Factors That Relate to the Persistence of First-Generation Undergraduate Students in a Public University

    ERIC Educational Resources Information Center

    Thachil, Shoba Anne

    2013-01-01

    This study examined factors that relate to the persistence of first-generation undergraduate students in a 4-year public university in the Southeastern United States. Results were analyzed from a 2011 two-part survey: CARES-I (College Assessment of Readiness for Entering Students-Intent) and CARES-A (College Assessment of Readiness for Entering…

  15. Factors Influencing College Decision-Making for First-Generation Appalachian Students

    ERIC Educational Resources Information Center

    Wood, Kristy Lynn

    2012-01-01

    This investigation determined the degree of importance for selected personal-psychological, academic, peer, financial, and family factors influencing the decision to attend college by first-generation, Appalachian (FGA) sophomore students. Outcomes were further related to the degree of academic and social integration in college and the likelihood…

  16. Generation Y Student-Teachers' Motivational Factors: Retention Implications for K-12 Educational Leaders

    ERIC Educational Resources Information Center

    Bontempo, Brian

    2010-01-01

    Generation Y represents a growing number of student-teachers who will impact the future of educational practice, yet little research has been conducted for this demographic group. The purpose of this mixed-method study was to identify motivational factors of neophyte teachers and the retention implications these findings had on Kindergarten…

  17. Docetaxel, Cisplatin, Pegfilgrastim, and Erlotinib Hydrochloride in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-11-13

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  18. Expanding the phenotype of mutations in DICER1: mosaic missense mutations in the RNase IIIb domain of DICER1 cause GLOW syndrome

    PubMed Central

    Klein, Steven; Lee, Hane; Ghahremani, Shahnaz; Kempert, Pamela; Ischander, Mariam; Teitell, Michael A; Nelson, Stanley F; Martinez-Agosto, Julian A

    2015-01-01

    Background Constitutional DICER1 mutations have been associated with pleuropulmonary blastoma, cystic nephroma, Sertoli-Leydig tumours and multinodular goitres, while somatic DICER1 mutations have been reported in additional tumour types. Here we report a novel syndrome termed GLOW, an acronym for its core phenotypic findings, which include Global developmental delay, Lung cysts, Overgrowth and Wilms tumour caused by mutations in the RNase IIIb domain of DICER1. Methods and results We performed whole exome sequencing on peripheral mononuclear blood cells of an affected proband and identified a de novo missense mutation in the RNase IIIb domain of DICER1. We confirmed an additional de novo missense mutation in the same domain of an unrelated case by Sanger sequencing. These missense mutations in the RNase IIIb domain of DICER1 are suspected to affect one of four metal binding sites located within this domain. Pyrosequencing was used to determine the relative abundance of mutant alleles in various tissue types. The relative mutation abundance is highest in Wilms tumour and unaffected kidney samples when compared with blood, confirming that the mutation is mosaic. Finally, we performed bioinformatic analysis of microRNAs expressed in murine cells carrying specific Dicer1 RNase IIIb domain metal binding site-associated mutations. We have identified a subset of 3p microRNAs that are overexpressed whose target genes are over-represented in mTOR, MAPK and TGF-β signalling pathways. Conclusions We propose that mutations affecting the metal binding sites of the DICER1 RNase IIIb domain alter the balance of 3p and 5p microRNAs leading to deregulation of these growth signalling pathways, causing a novel human overgrowth syndrome. PMID:24676357

  19. Generation of Bondarenko F factors with MCNP5 for use in scale transport codes

    SciTech Connect

    Hart, S.; Maldonado, G. I.

    2012-07-01

    Generally there are three methods of cross-section processing available when using the Scale computer code. They are NITAWL, BONAMI, and CENTRM, with CENTRM being the most common and accurate, but computationally expensive. In order to improve the accuracy of BONAMI (which uses the Bondarenko Method), new Bondarenko/F Factors were to be generated that will smooth out the current F Factors that are being generated using CENTRM. The case discussed here involves using a dedicated Monte Carlo code (MCNP5) to calculate the transport solution from which shielded cross-sections can be produced directly for the transport geometry/mesh. A simple program was created to parse and collect the tallied cross-sections from the MCNP output, which was fed into a modified CLAROL input (a module that replaces or adds data in an AMPX master library), which used the cross-sections obtained from MCNP to calculate new F-factors and update the SCALE library. This approach allows the use of other methods to generate the shielded cross-sections and for easy comparison to existing results. Initial proof-of-principle calculations were carried out for an various cases using various transport solvers, such as NEWT, KENO, and XSDRN, with BONAMI in SCALE. Poor results were obtained using cross-sections generated using infinite homogeneous cases, but good results were obtained by using pin cells in an infinite lattice. (authors)

  20. The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

    SciTech Connect

    Higginson, Daniel S.; Chen, Ronald C.; Tracton, Gregg; Morris, David E.; Halle, Jan; Rosenman, Julian G.; Stefanescu, Mihaela; Pham, Erica; Socinski, Mark A.; Marks, Lawrence B.

    2012-11-01

    Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods and Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1

  1. Factors associated with involvement in nonmetropolitan LGBTQ organizations: Proximity? Generativity? Minority stress? Social location?

    PubMed

    Paceley, Megan S; Oswald, Ramona Faith; Hardesty, Jennifer L

    2014-01-01

    Little is known about involvement in LGBTQ organizations. Factors associated with involvement in nonmetropolitan LGBTQ organizations were examined using logistic regression and survey data from 426 LGBTQ individuals residing in a nonmetropolitan region. Involvement was examined in five types of organizations (professional, social/recreational, religious, political, and community center/charity). The same model testing proximity, generativity, minority stress, and social location hypotheses was repeated for each organization type. Results demonstrate that the generativity hypothesis is most strongly supported. Indeed, emotional attachment to the LGBTQ community significantly increased the odds of involvement in every type of organization. However, the factors associated with involvement otherwise differed by organization type. Implications for organizational leaders are discussed.

  2. A global fouling factor methodology for analyzing steam generator thermal performance degradation

    SciTech Connect

    Kreider, M.A.; White, G.A.; Varrin, R.D. Jr.

    1998-06-01

    Over the past few years, steam generator (SG) thermal performance degradation has led to decreased plant efficiency and power output at numerous PWR nuclear power plants with recirculating-type SGs. The authors have developed and implemented methodologies for quantitatively evaluating the various sources of SG performance degradation, both internal and external to the SG pressure boundary. These methodologies include computation of the global fouling factor history, evaluation of secondary deposit thermal resistance using deposit characterization data, and consideration of pressure loss causes unrelated to the tube bundle, such as hot-leg temperature streaming and SG moisture separator fouling. In order to evaluate the utility of the global fouling factor methodology, the authors performed case studies for a number of PWR SG designs. Key results from two of these studies are presented here. In tandem with the fouling-factor analyses, a study evaluated for each plant the potential causes of pressure loss. The combined results of the global fouling factor calculations and the pressure-loss evaluations demonstrated two key points: (1) that the available thermal margin against fouling, which can vary substantially from plant to plant, has an important bearing on whether a given plant exhibits losses in electrical generating capacity, and (2) that a wide variety of causes can result in SG thermal performance degradation.

  3. Overlap functions, spectroscopic factors, and asymptotic normalization coefficients generated by a shell-model source term

    SciTech Connect

    Timofeyuk, N. K.

    2010-06-15

    Overlap functions for one-nucleon removal are calculated as solutions of the inhomogeneous equation. The source term for this equation is generated by the 0(Planck constant/2pi)omega no-core shell-model wave functions and the effective nucleon-nucleon (NN) interactions that fit oscillator matrix elements derived from the NN scattering data. For the lightest A<=4 nuclei this method gives reasonable agreement with exact ab initio calculations. For 4factors obtained show systematic deviation from the corresponding shell-model values. This deviation correlates with nucleon separation energies and follows a similar trend seen in the reduction factor of the nucleon knockout cross sections. Comparison with the overlap functions and spectroscopic factors obtained in the variational Monte Carlo method is presented and discussed.

  4. Factors affecting alkalinity generation by successive alkalinity-producing systems: regression analysis.

    PubMed

    Jage, C R; Zipper, C E; Noble, R

    2001-01-01

    Use of successive alkalinity-producing systems (SAPS) for treatment of acidic mine drainage (AMD) has grown in recent years. However, inconsistent performance has hampered widespread acceptance of this technology. This research was conducted to determine the influence of system design and influent AMD chemistry on net alkalinity generation by SAPS. Monthly observations were obtained from eight SAPS cells in southern West Virginia and southwestern Virginia. Analysis of these data revealed strong, positive correlations between net alkalinity generation and three variables: the natural log of limestone residence time, influent dissolved Fe concentration, and influent non-Mn acidity. A statistical model was constructed to describe SAPS performance. Subsequent analysis of data obtained from five systems in western Pennsylvania (calibration data set) was used to reevaluate the model form, and the statistical model was adjusted using the combined data sets. Limestone residence time exhibited a strong, positive logarithmic correlation with net alkalinity generation, indicating net alkalinity generation occurs most rapidly within the first few hours of AMD-limestone contact and additional residence time yields diminishing gains in treatment. Influent Fe and non-Mn acidity concentrations both show strong positive linear relationships with net alkalinity generation, reflecting the increased solubility of limestone under acidic conditions. These relationships were present in the original and the calibration data sets, separately, and in the statistical model derived from the combined data set. In the combined data set, these three factors accounted for 68% of the variability in SAPS systems performance. PMID:11401248

  5. Operational water consumption and withdrawal factors for electricity generating technologies: a review of existing literature

    NASA Astrophysics Data System (ADS)

    Macknick, J.; Newmark, R.; Heath, G.; Hallett, K. C.

    2012-12-01

    This report provides estimates of operational water withdrawal and water consumption factors for electricity generating technologies in the United States. Estimates of water factors were collected from published primary literature and were not modified except for unit conversions. The water factors presented may be useful in modeling and policy analyses where reliable power plant level data are not available. Major findings of the report include: water withdrawal and consumption factors vary greatly across and within fuel technologies, and water factors show greater agreement when organized according to cooling technologies as opposed to fuel technologies; a transition to a less carbon-intensive electricity sector could result in either an increase or a decrease in water use, depending on the choice of technologies and cooling systems employed; concentrating solar power technologies and coal facilities with carbon capture and sequestration capabilities have the highest water consumption values when using a recirculating cooling system; and non-thermal renewables, such as photovoltaics and wind, have the lowest water consumption factors. Improved power plant data and further studies into the water requirements of energy technologies in different climatic regions would facilitate greater resolution in analyses of water impacts of future energy and economic scenarios. This report provides the foundation for conducting water use impact assessments of the power sector while also identifying gaps in data that could guide future research.

  6. Improvement of force factor of magnetostrictive vibration power generator for high efficiency

    SciTech Connect

    Kita, Shota Ueno, Toshiyuki; Yamada, Sotoshi

    2015-05-07

    We develop high power magnetostrictive vibration power generator for battery-free wireless electronics. The generator is based on a cantilever of parallel beam structure consisting of coil-wound Galfenol and stainless plates with permanent magnet for bias. Oscillating force exerted on the tip bends the cantilever in vibration yields stress variation of Galfenol plate, which causes flux variation and generates voltage on coil due to the law of induction. This generator has advantages over conventional, such as piezoelectric or moving magnet types, in the point of high efficiency, highly robust, and low electrical impedance. Our concern is the improvement of energy conversion efficiency dependent on the dimension. Especially, force factor, the conversion ratio of the electromotive force (voltage) on the tip velocity in vibration, has an important role in energy conversion process. First, the theoretical value of the force factor is formulated and then the validity was verified by experiments, where we compare four types of prototype with parameters of the dimension using 7.0 × 1.5 × 50 mm beams of Galfenol with 1606-turn wound coil. In addition, the energy conversion efficiency of the prototypes depending on load resistance was measured. The most efficient prototype exhibits the maximum instantaneous power of 0.73 W and energy of 4.7 mJ at a free vibration of frequency of 202 Hz in the case of applied force is 25 N. Further, it was found that energy conversion efficiency depends not only on the force factor but also on the damping (mechanical loss) of the vibration.

  7. Improvement of force factor of magnetostrictive vibration power generator for high efficiency

    NASA Astrophysics Data System (ADS)

    Kita, Shota; Ueno, Toshiyuki; Yamada, Sotoshi

    2015-05-01

    We develop high power magnetostrictive vibration power generator for battery-free wireless electronics. The generator is based on a cantilever of parallel beam structure consisting of coil-wound Galfenol and stainless plates with permanent magnet for bias. Oscillating force exerted on the tip bends the cantilever in vibration yields stress variation of Galfenol plate, which causes flux variation and generates voltage on coil due to the law of induction. This generator has advantages over conventional, such as piezoelectric or moving magnet types, in the point of high efficiency, highly robust, and low electrical impedance. Our concern is the improvement of energy conversion efficiency dependent on the dimension. Especially, force factor, the conversion ratio of the electromotive force (voltage) on the tip velocity in vibration, has an important role in energy conversion process. First, the theoretical value of the force factor is formulated and then the validity was verified by experiments, where we compare four types of prototype with parameters of the dimension using 7.0 × 1.5 × 50 mm beams of Galfenol with 1606-turn wound coil. In addition, the energy conversion efficiency of the prototypes depending on load resistance was measured. The most efficient prototype exhibits the maximum instantaneous power of 0.73 W and energy of 4.7 mJ at a free vibration of frequency of 202 Hz in the case of applied force is 25 N. Further, it was found that energy conversion efficiency depends not only on the force factor but also on the damping (mechanical loss) of the vibration.

  8. Mexican American First-Generation Students' Perceptions of Siblings and Additional Factors Influencing Their College Choice Process

    ERIC Educational Resources Information Center

    Elias McAllister, Dora

    2012-01-01

    The purpose of this study was to understand the factors influencing the college choice process of Mexican American first-generation students who had an older sibling with college experience. While a considerable amount of research exists on factors influencing the college choice process of first-generation college students, and a few studies…

  9. Factors affecting the appreciation generated through applying human factors/ergonomics (HFE) principles to systems of work.

    PubMed

    So, R H Y; Lam, S T

    2014-01-01

    This retrospective study examined the levels of appreciation (applause) given by clients to Human Factors/Ergonomic (HFE) specialists after they have modified the systems of work. Thirteen non-academic projects were chosen because the HFE interventions involved changed the way workers work at their workplaces. Companies involved range from multi-national corporations and military organizations with thousands of employees to small trading companies with less than 10 employees. In 5 cases the HFE recommendations were fully adopted and well appreciated. In 4 they were largely ignored and not appreciated, with partial adoption and some appreciation in the other 4 cases. Three factors that predict appreciation were identified: (i) alignment between the benefits HFE can provide and the project's key performance indices; (ii) awareness of HFE among the client's senior management; and (iii) a team organization appropriate for applying HFE recommendations. Having an HFE specialist on the client's side can greatly increase levels of appreciation, but lack of such a specialist will not affect levels of appreciation. A clear contractual requirement for HFE intervention does not promote appreciation significantly, but its absence can greatly reduce levels of appreciation. These relationships are discussed using the Kano's model of quality. Means to generate greater appreciation of the benefits of HFE are discussed.

  10. Factors affecting the appreciation generated through applying human factors/ergonomics (HFE) principles to systems of work.

    PubMed

    So, R H Y; Lam, S T

    2014-01-01

    This retrospective study examined the levels of appreciation (applause) given by clients to Human Factors/Ergonomic (HFE) specialists after they have modified the systems of work. Thirteen non-academic projects were chosen because the HFE interventions involved changed the way workers work at their workplaces. Companies involved range from multi-national corporations and military organizations with thousands of employees to small trading companies with less than 10 employees. In 5 cases the HFE recommendations were fully adopted and well appreciated. In 4 they were largely ignored and not appreciated, with partial adoption and some appreciation in the other 4 cases. Three factors that predict appreciation were identified: (i) alignment between the benefits HFE can provide and the project's key performance indices; (ii) awareness of HFE among the client's senior management; and (iii) a team organization appropriate for applying HFE recommendations. Having an HFE specialist on the client's side can greatly increase levels of appreciation, but lack of such a specialist will not affect levels of appreciation. A clear contractual requirement for HFE intervention does not promote appreciation significantly, but its absence can greatly reduce levels of appreciation. These relationships are discussed using the Kano's model of quality. Means to generate greater appreciation of the benefits of HFE are discussed. PMID:23726141

  11. The influence of local order at a crystal-melt interface on the A IIIB V crystal growth

    NASA Astrophysics Data System (ADS)

    Skripnikov, V. A.; Khukhryansky, Yu. P.; Savchenko, V. A.; Kartavykh, A. V.

    2008-07-01

    An alternative approach to the study of crystallization process of the A IIIB V semiconductor compounds taking place at the "crystal-melt" interface has been considered in this paper. The influence of the short-range order in the interface region on the crystallization process has been studied at the atomic level. An elementary growth cell representing a system of five atoms, two of them are A III atoms belonging to a substrate, two other A III atoms and the fifth B V pertain to a solution-melt, has been proposed. Positions of the A III atoms belonging to the solution-melt are distributed in such a way that the resulting potential of the B V atom proves to be double well. Transitions of the B V atoms in such double-well potentials lead to crystallization. Taking the semiconductor compound GaP as an example, the potential energies of the pair interaction in the P 2, GaP and Ga 2 molecules are determined as functions of the interatomic distance. Based on these function dependences, the mean values of the double-well potential parameters are calculated. This allows to determine the mean rate of the elementary crystallization events at the interface. Some problems of the growing crystal morphology are discussed.

  12. Definitive radiotherapy with concurrent oncothermia for stage IIIB non-small-cell lung cancer: A case report

    PubMed Central

    YEO, SEUNG-GU

    2015-01-01

    Hyperthermia enhances the susceptibility of tumors to radiotherapy (RT) and chemotherapy. Oncothermia, also known as electro-hyperthermia, is a new treatment modality developed to overcome the problems of traditional hyperthermia by selectively delivering energy to the malignant tissues. The present study reports the outcome of combined oncothermia and RT in a 75-year-old patient with stage IIIB non-small-cell lung cancer (NSCLC). Due to the advanced age and the performance status of the patient, the combination of systemic chemotherapy and RT was deemed infeasible; therefore, the patient instead decided to undergo oncothermia concurrently with definitive RT. The RT was administered at a dose of 64.8 Gy in 36 fractions using a three-dimensional conformal plan technique. Oncothermia was started concomitantly with RT and was performed for 60 min per session, two sessions per week, for a total of 12 sessions. No severe toxicities developed, with the exception of mild odynophagia, which resolved soon after the treatments. Follow-up computed tomography showed complete tumor response, and the patient was alive with no evidence of the disease 18 months after the completion of the treatment. In conclusion, the present case report suggests that oncothermia combined with RT, with the former possessing radiosensitizing potential and no additional toxicities, may be a promising alternative for advanced-age and/or frail patients with locally advanced NSCLC. PMID:26622391

  13. CCR5/CD4/CXCR4 oligomerization prevents HIV-1 gp120IIIB binding to the cell surface

    PubMed Central

    Martínez-Muñoz, Laura; Barroso, Rubén; Dyrhaug, Sunniva Y.; Navarro, Gemma; Lucas, Pilar; Soriano, Silvia F.; Vega, Beatriz; Costas, Coloma; Muñoz-Fernández, M. Ángeles; Santiago, César; Frade, José Miguel Rodríguez; Franco, Rafael; Mellado, Mario

    2014-01-01

    CCR5 and CXCR4, the respective cell surface coreceptors of R5 and X4 HIV-1 strains, both form heterodimers with CD4, the principal HIV-1 receptor. Using several resonance energy transfer techniques, we determined that CD4, CXCR4, and CCR5 formed heterotrimers, and that CCR5 coexpression altered the conformation of both CXCR4/CXCR4 homodimers and CD4/CXCR4 heterodimers. As a result, binding of the HIV-1 envelope protein gp120IIIB to the CD4/CXCR4/CCR5 heterooligomer was negligible, and the gp120-induced cytoskeletal rearrangements necessary for HIV-1 entry were prevented. CCR5 reduced HIV-1 envelope-induced CD4/CXCR4-mediated cell-cell fusion. In nucleofected Jurkat CD4 cells and primary human CD4+ T cells, CCR5 expression led to a reduction in X4 HIV-1 infectivity. These findings can help to understand why X4 HIV-1 strains infection affect T-cell types differently during AIDS development and indicate that receptor oligomerization might be a target for previously unidentified therapeutic approaches for AIDS intervention. PMID:24778234

  14. Structure and activity of the RNA-targeting Type III-B CRISPR-Cas complex of Thermus thermophilus

    PubMed Central

    Zhu, Yifan; Taylor, David W.; van Duijn, Esther; Barendregt, Arjan; Vlot, Marnix; Koehorst, Jasper J.; Sakamoto, Keiko; Masuda, Akiko; Dohmae, Naoshi; Schaap, Peter J.; Doudna, Jennifer A.; Heck, Albert J.R.; Yonekura, Koji; van der Oost, John; Shinkai, Akeo

    2014-01-01

    Summary The CRISPR-Cas system is a prokaryotic host defense system against genetic elements. The Type III-B CRISPR-Cas system of the bacterium Thermus thermophilus, the TtCmr complex, is composed of six different protein subunits (Cmr1-6) and one crRNA with a stoichiometry of Cmr112131445361:crRNA1. The TtCmr complex co-purifies with crRNA species of 40 and 46 nt, originating from a distinct subset of CRISPR loci and spacers. The TtCmr complex cleaves the target RNA at multiple sites with 6 nt intervals via a 5’ ruler mechanism. Electron microscopy revealed that the structure of TtCmr resembles a ‘sea worm’ and is composed of a Cmr2-3 heterodimer ‘tail’, a helical backbone of Cmr4 subunits capped by Cmr5 subunits, and a curled ‘head’ containing Cmr1 and Cmr6. Despite having a backbone of only four Cmr4 subunits and being both longer and narrower, the overall architecture of TtCmr resembles that of Type I Cascade complexes. PMID:24119403

  15. Bipartite recognition of target RNAs activates DNA cleavage by the Type III-B CRISPR–Cas system

    PubMed Central

    Elmore, Joshua R.; Sheppard, Nolan F.; Ramia, Nancy; Deighan, Trace; Li, Hong; Terns, Rebecca M.; Terns, Michael P.

    2016-01-01

    CRISPR–Cas systems eliminate nucleic acid invaders in bacteria and archaea. The effector complex of the Type III-B Cmr system cleaves invader RNAs recognized by the CRISPR RNA (crRNA ) of the complex. Here we show that invader RNAs also activate the Cmr complex to cleave DNA. As has been observed for other Type III systems, Cmr eliminates plasmid invaders in Pyrococcus furiosus by a mechanism that depends on transcription of the crRNA target sequence within the plasmid. Notably, we found that the target RNA per se induces DNA cleavage by the Cmr complex in vitro. DNA cleavage activity does not depend on cleavage of the target RNA but notably does require the presence of a short sequence adjacent to the target sequence within the activating target RNA (rPAM [RNA protospacer-adjacent motif]). The activated complex does not require a target sequence (or a PAM) in the DNA substrate. Plasmid elimination by the P. furiosus Cmr system also does not require the Csx1 (CRISPR-associated Rossman fold [CARF] superfamily) protein. Plasmid silencing depends on the HD nuclease and Palm domains of the Cmr2 (Cas10 superfamily) protein. The results establish the Cmr complex as a novel DNA nuclease activated by invader RNAs containing a crRNA target sequence and a rPAM. PMID:26848045

  16. Delayed Type IIIb endoleak secondary to graft fabric tear 7 years following implantation of a Medtronic Talent endovascular aortic device: A case report and review of the literature

    PubMed Central

    Kansal, Vinay; Nagpal, Sudhir

    2016-01-01

    Objectives: To report a rare case of delayed Type IIIb endoleak secondary to fabric tear following implantation of a Medtronic Talent endovascular device. Methods: A 83-year old gentleman underwent elective endovascular aneurysm repair for infrarenal abdominal aortic aneurysm with a Medtronic bifurcated stent graft in 2008. Results: Seven years after the initial repair, imaging surveillance revealed significant endoleak and brisk aneurysm sac expansion due to Type IIIb endoleak secondary to endograft limb fabric tear. Conclusions: This case illustrates the imperative role of imaging surveillance in detection of long-term endovascular aneurysm repair complications. Furthermore, we discuss exclusion of the graft tear with aortouniiliac stent grafting as the treatment for this complication. PMID:27708782

  17. Generation of a Felinized Swine Endothelial Cell Line by Expression of Feline Decay-Accelerating Factor

    PubMed Central

    Izuhara, Luna; Tatsumi, Norifumi; Miyagawa, Shuji; Iwai, Satomi; Watanabe, Masahito; Yamanaka, Shuichiro; Katsuoka, Yuichi; Nagashima, Hiroshi; Okano, Hirotaka J.; Yokoo, Takashi

    2015-01-01

    Embryonic stem cell research has facilitated the generation of many cell types for the production of tissues and organs for both humans and companion animals. Because ≥30% of pet cats suffer from chronic kidney disease (CKD), xenotransplantation between pigs and cats has been studied. For a successful pig to cat xenotransplant, the immune reaction must be overcome, especially hyperacute rejection. In this study, we isolated the gene for feline decay-accelerating factor (fDAF), an inhibitor of complement proteins, and transfected a swine endothelial cell line with fDAF to “felinize” the pig cells. These fDAF-expressing cells were resistant to feline serum containing anti-pig antibodies, suggesting that felinized pig cells were resistant to hyperacute rejection. Our results suggest that a “felinized” pig kidney can be generated for the treatment of CKD in cats in the future. PMID:25671605

  18. A Progenitor Cell Expressing Transcription Factor RORγt Generates All Human Innate Lymphoid Cell Subsets.

    PubMed

    Scoville, Steven D; Mundy-Bosse, Bethany L; Zhang, Michael H; Chen, Li; Zhang, Xiaoli; Keller, Karen A; Hughes, Tiffany; Chen, Luxi; Cheng, Stephanie; Bergin, Stephen M; Mao, Hsiaoyin C; McClory, Susan; Yu, Jianhua; Carson, William E; Caligiuri, Michael A; Freud, Aharon G

    2016-05-17

    The current model of murine innate lymphoid cell (ILC) development holds that mouse ILCs are derived downstream of the common lymphoid progenitor through lineage-restricted progenitors. However, corresponding lineage-restricted progenitors in humans have yet to be discovered. Here we identified a progenitor population in human secondary lymphoid tissues (SLTs) that expressed the transcription factor RORγt and was unique in its ability to generate all known ILC subsets, including natural killer (NK) cells, but not other leukocyte populations. In contrast to murine fate-mapping data, which indicate that only ILC3s express Rorγt, these human progenitor cells as well as human peripheral blood NK cells and all mature ILC populations expressed RORγt. Thus, all human ILCs can be generated through an RORγt(+) developmental pathway from a common progenitor in SLTs. These findings help establish the developmental signals and pathways involved in human ILC development.

  19. Generation of a felinized swine endothelial cell line by expression of feline decay-accelerating factor.

    PubMed

    Izuhara, Luna; Tatsumi, Norifumi; Miyagawa, Shuji; Iwai, Satomi; Watanabe, Masahito; Yamanaka, Shuichiro; Katsuoka, Yuichi; Nagashima, Hiroshi; Okano, Hirotaka J; Yokoo, Takashi

    2015-01-01

    Embryonic stem cell research has facilitated the generation of many cell types for the production of tissues and organs for both humans and companion animals. Because ≥30% of pet cats suffer from chronic kidney disease (CKD), xenotransplantation between pigs and cats has been studied. For a successful pig to cat xenotransplant, the immune reaction must be overcome, especially hyperacute rejection. In this study, we isolated the gene for feline decay-accelerating factor (fDAF), an inhibitor of complement proteins, and transfected a swine endothelial cell line with fDAF to "felinize" the pig cells. These fDAF-expressing cells were resistant to feline serum containing anti-pig antibodies, suggesting that felinized pig cells were resistant to hyperacute rejection. Our results suggest that a "felinized" pig kidney can be generated for the treatment of CKD in cats in the future. PMID:25671605

  20. A clinical study evaluating dendritic and cytokine-induced killer cells combined with concurrent radiochemotherapy for stage IIIB non-small cell lung cancer.

    PubMed

    Zhu, X P; Xu, Y H; Zhou, J; Pan, X F

    2015-08-28

    To compare the efficacy of dendritic and cytokine-induced killer cells (DC-CIK) therapy combined with concurrent radiochemotherapy on stage IIIB non-small cell lung cancer. Sixty-three patients with stage IIIB non-small cell lung cancer were randomly divided into the study and control groups. The study group, comprising 30 patients, was treated with DC-CIK combined with docetaxel-cisplatin chemotherapy and synchronization conformal radiotherapy. The control group including 33 patients was only treated with docetaxel-cisplatin chemotherapy and synchronization conformal radiotherapy. The efficacy, Karnofsky performance score (KPS), tumor markers, 6-month and 12-month survival rate, T cell subsets, and adverse reactions of the two groups were compared. The response rate of the study group was 83.3% (25/30), and that of the control group was only 54.5% (18/33). Furthermore, the KPS, T cell subsets, and 12-month survival rate was significantly higher in the study group, and there were significant differences between the two groups. The two groups had no significant difference in adverse reactions. The combined DC-CIK therapy, with synchronous radiotherapy and chemotherapy to treat stage IIIB non-small cell lung cancer was superior to single synchronous radiotherapy and chemotherapy. The combined therapy can improve the life quality and prolong the survival time of the patients.

  1. Mutation Scanning of D1705 and D1709 in the RNAse IIIb Domain of MicroRNA Processing Enzyme Dicer in Cutaneous Melanoma.

    PubMed

    Sand, Michael; Bechara, Falk G; Skrygan, Marina; Sand, Daniel; Gambichler, Thilo; Bromba, Michael; Stockfleth, Eggert; Hessam, Schapoor

    2016-07-01

    Since the discovery of microRNAs (miRNAs) there have been performed several studies showing perturbations in the expression of miRNAs and the miRNA expression machinery in cutaneous melanoma. Dicer, a pivotal cytosolic enzyme of miRNA maturation has shown to be affected by both somatic and germline mutations in a variety of cancers. Recent studies have shown that recurrent somatic mutations of Dicer frequently affect the metal-ion-binding sites D1709 and D1705 of its RNase IIIb domain, therefore called hot spot mutations. The present study investigates metal-ion-binding sites D1709 and D1705 of the Dicer RNase IIIb domain in cutaneous melanomas and melanoma metastasis by Sanger sequencing. All investigated samples showed wildtype sequence and no single mutation was detected. The miRNA processing enzyme Dicer of melanoma and melanoma metastasis does not appear to be affected by mutation in the metal-ion-binding sites D1709 and D1705 of its RNase IIIb domain. PMID:26683837

  2. Generations.

    PubMed

    Chambers, David W

    2005-01-01

    Groups naturally promote their strengths and prefer values and rules that give them an identity and an advantage. This shows up as generational tensions across cohorts who share common experiences, including common elders. Dramatic cultural events in America since 1925 can help create an understanding of the differing value structures of the Silents, the Boomers, Gen Xers, and the Millennials. Differences in how these generations see motivation and values, fundamental reality, relations with others, and work are presented, as are some applications of these differences to the dental profession. PMID:16623137

  3. Using data linkage to generate 30-day crash-fatality adjustment factors for Taiwan.

    PubMed

    Lai, Ching-Huei; Huang, Wei-Shin; Chang, Kai-Kuo; Jeng, Ming-Chang; Doong, Ji-Liang

    2006-07-01

    Different countries have their own police reporting time standards for counting the number of fatalities in reported crashes. A rapid estimation method (such as adjustment factor) for the comparison is important. The data-linkage technique was used to combine police-reported crash data and vital registration data, in order to generate 30-day fatality adjustment factors for various reporting time standards, which could also shed light on the fatal injury trend over time. The major findings were as follows. Firstly, a conservative 30-day fatality adjustment factor for the first day (or 24 h) would be 1.54 (or 1.35) in an area with a large motorcycle population, like Taiwan. This produced 20-40% higher 30-day fatalities than UK Transport Research Laboratory predicted, and 15-25% higher fatalities than those in Europe/Japan. Secondly, after excluding motorcycle impacts, the Taiwanese factors suggested 8-14% higher fatalities within 30 days than those in Europe/Japan. Third, motorcycle fatalities influenced the overall 30-day fatality trend within 3 days. In the future, both the police under-reporting problem and the motorcycle/overall fatal injury pattern within 3 days after crashing in developing countries like Taiwan merit further investigation. PMID:16430844

  4. Fucosylated chondroitin sulfate inhibits plasma thrombin generation via targeting of the factor IXa heparin-binding exosite.

    PubMed

    Buyue, Yang; Sheehan, John P

    2009-10-01

    Depolymerized holothurian glycosaminoglycan (DHG) is a fucosylated chondroitin sulfate with antithrombin-independent antithrombotic properties. Heparin cofactor II (HCII)-dependent and -independent mechanisms for DHG inhibition of plasma thrombin generation were evaluated. When thrombin generation was initiated with 0.2 pM tissue factor (TF), the half maximal effective concentration (EC(50)) for DHG inhibition was identical in mock- or HCII-depleted plasma, suggesting a serpin-independent mechanism. In the presence of excess TF, the EC(50) for DHG was increased 13- to 27-fold, suggesting inhibition was dependent on intrinsic tenase (factor IXa-factor VIIIa) components. In factor VIII-deficient plasma supplemented with 700 pM factor VIII or VIIIa, and factor IX-deficient plasma supplemented with plasma-derived factor IX or 100 pM factor IXa, the EC(50) for DHG was similar. Thus, cofactor and zymogen activation did not contribute to DHG inhibition of thrombin generation. Factor IX-deficient plasma supplemented with mutant factor IX(a) proteins demonstrated resistance to DHG inhibition of thrombin generation [factor IX(a) R233A > R170A > WT] that inversely correlated with protease-heparin affinity. These results replicate the effect of these mutations with purified intrinsic tenase components, and establish the factor IXa heparin-binding exosite as the relevant molecular target for inhibition by DHG. Glycosaminoglycan-mediated intrinsic tenase inhibition is a novel antithrombotic mechanism with physiologic and therapeutic applications.

  5. Enhancing factors of electricity generation in a microbial fuel cell using Geobacter sulfurreducens.

    PubMed

    Kim, Mi-Sun; Cha, Jaehwan; Kim, Dong-Hoon

    2012-10-01

    In this study, we investigated various cultural and operational factors to enhance electricity generation in a microbial fuel cell (MFC) using Geobacter sulfurreducens. The pure culture of G. sulfurreducens was cultivated using various substrates including acetate, malate, succinate, and butyrate, with fumarate as an electron acceptor. Cell growth was observed only in acetate-fed medium, when the cell concentrations increased 4-fold for 3 days. A high acetate concentration suppressed electricity generation. As the acetate concentration was increased from 5 to 20 mM, the power density dropped from 16 to 13 mW/m2, whereas the coulombic efficiency (CE) declined by about half. The immobilization of G. sulfurreducens on the anode considerably reduced the enrichment period from 15 to 7 days. Using argon gas to create an anaerobic condition in the anode chamber led to increased pH, and electricity generation subsequently dropped. When the plain carbon paper cathode was replaced by Pt-coated carbon paper (0.5 mg Pt/cm2), the CE increased greatly from 39% to 83%.

  6. An alternative strategy to generate coding sequence of macrophage migration inhibitory factor-2 of Wuchereria bancrofti

    PubMed Central

    Chauhan, Nikhil; Hoti, S.L.

    2016-01-01

    Background & objectives: Different developmental stages of Wuchereria bancrofti, the major causal organism of lymphatic filariasis (LF), are difficult to obtain. Beside this limitation, to obtain complete coding sequence (CDS) of a gene one has to isolate mRNA and perform subsequent cDNA synthesis which is laborious and not successful at times. In this study, an alternative strategy employing polymerase chain reaction (PCR) was optimized and validated, to generate CDS of Macrophage migration Inhibitory Factor-2 (wbMIF-2), a gene expressed in the transition stage between L3 to L4. Methods: The genomic DNA of W. bancrofti microfilariae was extracted and used to amplify the full length wbMIF-2 gene (4.275 kb). This amplified product was used as a template for amplifying the exons separately, using the overlapping primers, which were then assembled through another round of PCR. Results: A simple strategy was developed based on PCR, which is used routinely in molecular biology laboratories. The amplified CDS of 363 bp of wbMIF-2 generated using genomic DNA splicing technique was devoid of any intronic sequence. Interpretation & conclusions: The cDNA of wbMIF-2 gene was successfully amplified from genomic DNA of microfilarial stage of W. bancrofti thus circumventing the use of inaccessible L3-L4 transitional stage of this parasite. This strategy is useful for generating CDS of genes from parasites that have restricted availability. PMID:27121522

  7. Generation of induced pluripotent stem cells from buffalo (Bubalus bubalis) fetal fibroblasts with buffalo defined factors.

    PubMed

    Deng, Yanfei; Liu, Qingyou; Luo, Chan; Chen, Shibei; Li, Xiangping; Wang, Caizhu; Liu, Zhenzhen; Lei, Xiaocan; Zhang, Huina; Sun, Hongliang; Lu, Fenghua; Jiang, Jianrong; Shi, Deshun

    2012-09-01

    Ectopically, expression of defined factors could reprogram mammalian somatic cells into induced pluripotent stem cells (iPSCs), which initiates a new strategy to obtain pluripotent stem cell lines. Attempts have been made to generate buffalo pluripotent stem cells by culturing primary germ cells or inner cell mass, but the efficiency is extremely low. Here, we report a successful method to reprogram buffalo fetal fibroblasts (BFFs) into pluripotent stem cells [buffalo induced pluripotent stem cell (biPSCs)] by transduction of buffalo defined factors (Oct4, Sox2, Klf4, and c-Myc) using retroviral vectors. The established biPSCs displayed typical morphological characteristics of pluripotent stem cells, normal karyotype, positive staining of alkaline phosphatase, and expressed pluripotent markers including Oct4, Sox2, Nanog, Lin28, E-Cadherin, SSEA-1, SSEA-4, TRA-1-81, STAT3, and FOXD3. They could form embryoid bodies (EBs) in vitro and teratomas after injecting into the nude BALB/C mice, and 3 germ layers were identified in the EBs and teratomas. Methylation assay revealed that the promoters of Oct4 and Nanog were hypomethylated in biPSCs compared with BFFs and pre-biPSCs, while the promoters of Sox2 and E-Cadherin were hypomethylated in both BFFs and biPSCs. Further, inhibiting p53 expression by coexpression of SV40 large T antigen and buffalo defined factors in BFFs or treating BFFs with p53 inhibitor pifithrin-a (PFT) could increase the efficiency of biPSCs generation up to 3-fold, and nuclear transfer embryos reconstructed with biPSCs could develop to blastocysts. These results indicate that BFFs can be reprogrammed into biPSCs by buffalo defined factors, and the generation efficiency of biPSCs can be increased by inhibition of p53 expression. These efforts will provide a feasible approach for investigating buffalo stem cell signal pathways, establishing buffalo stem cell lines, and producing genetic modification buffaloes in the future. PMID:22420535

  8. Socioeconomic and Sociodemographic Factors Associated with Asthma Related Outcomes in Early Childhood: The Generation R Study

    PubMed Central

    Hafkamp-de Groen, Esther; Sonnenschein-van der Voort, Agnes M. M.; Mackenbach, Johan P.; Duijts, Liesbeth; Jaddoe, Vincent W. V.; Moll, Henriëtte A.; Hofman, Albert; de Jongste, Johan C.; Raat, Hein

    2013-01-01

    Rationale Few studies have analyzed the association of socioeconomic and sociodemographic factors with asthma related outcomes in early childhood, including Fraction of exhaled Nitric Oxide (FeNO) and airway resistance (Rint). We examined the association of socioeconomic and sociodemographic factors with wheezing, asthma, FeNO and Rint at age 6 years. Additionally, the role of potential mediating factors was studied. Methods The study included 6717 children participating in The Generation R Study, a prospective population-based cohort study. Data on socioeconomic and sociodemographic factors, wheezing and asthma were obtained by questionnaires. FeNO and Rint were measured at the research center. Statistical analyses were performed using logistic and linear regression models. Results At age 6 years, 9% (456/5084) of the children had wheezing symptoms and 7% (328/4953) had asthma. Children from parents with financial difficulties had an increased risk of wheezing (adjusted Odds Ratio (aOR) = 1.63, 95% Confidence Interval (CI):1.18–2.24). Parental low education, paternal unemployment and child's male sex were associated with asthma, independent of other socioeconomic or sociodemographic factors (aOR = 1.63, 95% CI:1.24–2.15, aOR = 1.85, 95% CI:1.11–3.09, aOR = 1.58, 95% CI:1.24–2.01, respectively). No socioeconomic or gender differences in FeNO were found. The risks of wheezing, asthma, FeNO and Rint measurements differed between ethnic groups (p<0.05). Associations between paternal unemployment, child's sex, ethnicity and asthma related outcomes remained largely unexplained. Conclusions This study showed differences between the socioeconomic and sociodemographic correlates of wheezing and asthma compared to the correlates of FeNO and Rint at age 6 years. Several socioeconomic and sociodemographic factors were independently associated with wheezing and asthma. Child's ethnicity was the only factor independently associated with FeNO. We

  9. Key factors for assessing climate benefits of natural gas versus coal electricity generation

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaochun; Myhrvold, Nathan P.; Caldeira, Ken

    2014-11-01

    Assessing potential climate effects of natural gas versus coal electricity generation is complicated by the large number of factors reported in life cycle assessment studies, compounded by the large number of proposed climate metrics. Thus, there is a need to identify the key factors affecting the climate effects of natural gas versus coal electricity production, and to present these climate effects in as clear and transparent a way as possible. Here, we identify power plant efficiencies and methane leakage rates as the factors that explain most of the variance in greenhouse gas emissions by natural gas and coal power plants. Thus, we focus on the role of these factors in determining the relative merits of natural gas versus coal power plants. We develop a simple model estimating CO2 and CH4 emissions from natural gas and coal power plants, and resulting temperature change. Simple underlying physical changes can be obscured by abstract evaluation metrics, thus we focus our analysis on the time evolution of global mean temperature. We find that, during the period of plant operation, if there is substantial methane leakage, natural gas plants can produce greater near-term warming than coal plants with the same power output. However, if methane leakage rates are low and power plant efficiency is high, natural gas plants can produce some reduction in near-term warming. In the long term, natural gas power plants produce less warming than would occur with coal power plants. However, without carbon capture and storage natural gas power plants cannot achieve the deep reductions that would be required to avoid substantial contribution to additional global warming.

  10. Neutrophil elastase cleavage of human factor IX generates an activated factor IX-like product devoid of coagulant function.

    PubMed

    Samis, J A; Kam, E; Nesheim, M E; Giles, A R

    1998-08-15

    In preliminary studies, the generation of thrombin in vivo was found to induce a 92% loss of functional activity of factor IX (F.IX) despite the detection by Western blotting of a product resembling activated F.IX (F.IXa) and a 25% increase in F.IX antigen levels (Hoogendoorn et al, Thromb Haemost 69:1127, 1993 [abstr]). These changes were associated with evidence of increased elastase availability. To study the possibility that these two observations were related, a detailed physical and functional characterization of the hydrolysis of purified human F.IX by human neutrophil elastase (HNE) was performed in vitro. An activated partial thromboplastin time (aPTT) clotting assay demonstrated that, although HNE eliminated the potential of F.IX to be activated, it only marginally reduced the F.IXa activity. Reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) indicated that HNE treatment of F.IX generated cleavage products of 30 and 20 kD that could not be distinguished from the respective heavy and light chain peptides that were identified in parallel studies when F.IX was activated by activated bovine F.XI (F.XIa), one of its physiological activators. In addition, nonreducing SDS-PAGE demonstrated that HNE-treated F.IX formed no complexes with antithrombin III (ATIII) in the presence of heparin. Furthermore, HNE-treated F.IX was unable to (1) bind the active site probe p-aminobenzamidine; (2) hydrolyze the synthetic peptide substrate CH3SO2-Leu-Gly-Arg-p-nitroanilide; and (3) activate human factor X (F.X). In contrast to dansyl-Glu-Gly-Arg-chloromethyl ketone (dEGR)-inactivated F.IXa, HNE-treated F.IX (0.01 to 10,000 pmol/L) failed to inhibit the clotting activity of F.IXa (10 pmol/L) in the aPTT. NH2-terminal sequencing indicated that HNE cleaved human F.IX at Thr140, Thr144, Ile164, Thr172, and Val181. The cleavages at Thr140/Thr144 and at Thr172/Val181 are both very close to the normal F.XIa alpha-(Arg145) and beta-(Arg180) cleavage sites

  11. Glial cells generate neurons: the role of the transcription factor Pax6.

    PubMed

    Heins, Nico; Malatesta, Paolo; Cecconi, Francesco; Nakafuku, Masato; Tucker, Kerry Lee; Hack, Michael A; Chapouton, Prisca; Barde, Yves-Alain; Götz, Magdalena

    2002-04-01

    Radial glial cells, ubiquitous throughout the developing CNS, guide radially migrating neurons and are the precursors of astrocytes. Recent evidence indicates that radial glial cells also generate neurons in the developing cerebral cortex. Here we investigated the role of the transcription factor Pax6 expressed in cortical radial glia. We showed that radial glial cells isolated from the cortex of Pax6 mutant mice have a reduced neurogenic potential, whereas the neurogenic potential of non-radial glial precursors is not affected. Consistent with defects in only one neurogenic lineage, the number of neurons in the Pax6 mutant cortex in vivo is reduced by half. Conversely, retrovirally mediated Pax6 expression instructs neurogenesis even in astrocytes from postnatal cortex in vitro. These results demonstrated an important role of Pax6 as intrinsic fate determinant of the neurogenic potential of glial cells.

  12. Factors Associated With Electronic Cigarette Users’ Device Preferences and Transition From First Generation to Advanced Generation Devices

    PubMed Central

    Veldheer, Susan; Hrabovsky, Shari; Nichols, Travis T.; Wilson, Stephen J.; Foulds, Jonathan

    2015-01-01

    Introduction: Electronic cigarettes (e-cigs) are becoming increasingly popular but little is known about how e-cig users’ transition between the different device types and what device characteristics and preferences may influence the transition. Methods: Four thousand four hundred twenty-one experienced e-cig users completed an online survey about their e-cig use, devices, and preferences. Participants included in analysis were ever cigarette smokers who used an e-cig at least 30 days in their lifetime and who reported the type of their first and current e-cig device and the nicotine concentration of their liquid. Analyses focused on transitions between “first generation” devices (same size as a cigarette with no button) and “advanced generation” devices (larger than a cigarette with a manual button) and differences between current users of each device type. Results: Most e-cig users (n = 2603, 58.9%) began use with a first generation device, and of these users, 63.7% subsequently transitioned to current use of an advanced generation device. Among users who began use with an advanced generation device (n = 1818, 41.1%), only 5.7% transitioned to a first generation device. Seventy-seven percent of current advanced generation e-cig users switched to their current device in order to obtain a “more satisfying hit.” Battery capabilities and liquid flavor choices also influenced device choice. Conclusion: E-cig users commonly begin use with a device shaped like a cigarette and transition to a larger device with a more powerful battery, a button for manual activation and a wider choice of liquid flavors. PMID:25744966

  13. Modeling and analysis of PM2.5 generation for key factors identification in China

    NASA Astrophysics Data System (ADS)

    Xia, Dehong; Jiang, Binfan; Xie, Yulei

    2016-06-01

    Recently, the PM2.5 pollution in China has occurred frequently and caused widely concern. In order to identify the key factors for PM2.5 generation, the formation characteristics of PM2.5 would be revealed. A property of electric neutrality of PM2.5 was proposed under the least-energy principle and verified through electricity-charge calculation in this paper. It indicated that PM2.5 is formed by the effect of electromagnetic force, including the effect of ionic bond, hydrogen bond and polarization. According to the analysis of interactive forces among different chemical components, a simulation model is developed for describing the random process of PM2.5 generation. In addition, an orthogonal test with two levels and four factors has been designed and carried out through the proposed model. From the text analysis, PM2.5 would be looser and suspend longer in atmosphere due to Organic Compound (OC) existing (OC can reduce about 67% of PM2.5 density). Considering that NH4+ is the only cation in the main chemical components of PM2.5, it would be vital for anions (such as SO42- and NO3-) to aggregate together for facilitating PM2.5 growing. Therefore, in order to relieve PM2.5 pollution, control strategies for OC and NH4+ would be enhanced by government through improving the quality of oils and solvent products, decreasing the amount of nitrogenous fertilizer utilization, or changing the fertilizing environment from dry condition to wet condition.

  14. Factors Influencing the Creation of a Wiki Culture for Knowledge Management in a Cross-Generational Organizational Setting

    ERIC Educational Resources Information Center

    Macro, Kenneth L., Jr.

    2011-01-01

    Initiatives within organizations that promote sharing of knowledge may be hampered by generational differences. Research on relationships between generations and technology-based knowledge sharing campaigns provides little managerial guidance for practitioners. The purpose of this ethnographic study was to identify the factors that influence the…

  15. Generation and gene expression profiling of 48 transcription-factor-inducible mouse embryonic stem cell lines

    PubMed Central

    Yamamizu, Kohei; Sharov, Alexei A.; Piao, Yulan; Amano, Misa; Yu, Hong; Nishiyama, Akira; Dudekula, Dawood B.; Schlessinger, David; Ko, Minoru S. H.

    2016-01-01

    Mouse embryonic stem cells (ESCs) can differentiate into a wide range – and possibly all cell types in vitro, and thus provide an ideal platform to study systematically the action of transcription factors (TFs) in cell differentiation. Previously, we have generated and analyzed 137 TF-inducible mouse ESC lines. As an extension of this “NIA Mouse ESC Bank,” we generated and characterized 48 additional mouse ESC lines, in which single TFs in each line could be induced in a doxycycline-controllable manner. Together, with the previous ESC lines, the bank now comprises 185 TF-manipulable ESC lines (>10% of all mouse TFs). Global gene expression (transcriptome) profiling revealed that the induction of individual TFs in mouse ESCs for 48 hours shifts their transcriptomes toward specific differentiation fates (e.g., neural lineages by Myt1 Isl1, and St18; mesodermal lineages by Pitx1, Pitx2, Barhl2, and Lmx1a; white blood cells by Myb, Etv2, and Tbx6, and ovary by Pitx1, Pitx2, and Dmrtc2). These data also provide and lists of inferred target genes of each TF and possible functions of these TFs. The results demonstrate the utility of mouse ESC lines and their transcriptome data for understanding the mechanism of cell differentiation and the function of TFs. PMID:27150017

  16. Generation and characterization of a monoclonal antibody against canine tissue factor.

    PubMed

    Stokol, Tracy; Daddona, Janelle; DeLeonardis, Christine; Dong, Lynn; Wagner, Bettina

    2015-10-15

    Tissue factor (TF, coagulation factor III) has recently identified roles in innate immunity and cancer. We generated a murine mAb against canine TF (cTF) cloned from Madin-Darby canine kidney cells and expressed in Chinese Hamster Ovarian (CHO) cells, with an equine IL-4 tag. One clone was selected for purification based on initial screening of CHO cell supernatants. The mAb was further characterized with flow cytometry, immunofluorescent microscopy, immunoblotting and immunohistochemical staining of normal and neoplastic canine tissue. The mAb labeled high, but not low, TF-expressing canine breast cancer (CMT25) and osteosarcoma (HMPOS) cells with flow cytometry and immunofluorescent microscopy. Immunoblotting revealed a 42kDa protein with homogenized canine brain and CMT25, but not HMPOS, lysates. The mAb labeled renal tubules and glomeruli, intestinal and dermal epithelium, and arteriolar adventitial cells in frozen tissues. Using immunofluorescent microscopy, increased numbers of labeled PBMCs were observed after LPS stimulation. Our results indicate that the anti-cTF mAb detects a protein with the expected tissue distribution and molecular weight of TF in normal, LPS-stimulated and neoplastic canine cells. This mAb may prove useful for exploring the role of TF in neoplastic and infectious disorders in dogs. PMID:26187440

  17. Inhibition of the generation of thrombin and factor Xa by a fucoidan from the brown seaweed Ecklonia kurome.

    PubMed

    Nishino, T; Fukuda, A; Nagumo, T; Fujihara, M; Kaji, E

    1999-10-01

    The effects of a fucoidan (C-II), which was purified from the brown seaweed Ecklonia kurome, on the generation of thrombin and factor Xa have been investigated by measuring the amidolytic activities by using the respective specific chromogenic substrates in both plasma and purified systems. C-II inhibited significantly the generation of thrombin in both the intrinsic and the extrinsic pathways, although the intrinsic inhibitory effect by C-II was more remarkable than the extrinsic one. On the other hand, C-II was a good inhibitor of the factor Xa generation in the intrinsic pathway, while it was a poor one in the extrinsic pathway. In the purified systems C-II also inhibited the formation of prothrombin-activating complex (i.e., prothrombinase), but not its activity. The concentration of C-II required for 50% inhibition of thrombin generation was about one-tenth to one-seventh of that of the activity of the generated thrombin in plasma. These results indicate that C-II has an inhibitory effect on the generation of thrombin by blocking the formation of prothrombinase and by preventing the generation of intrinsic factor Xa in addition to its antithrombin activity, and also that the generation-inhibitory effect is more remarkable than C-II's enhancement effect on the antithrombin activity by heparin cofactor II in plasma.

  18. 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.

  19. Creating Novel Activated Factor XI Inhibitors through Fragment Based Lead Generation and Structure Aided Drug Design

    PubMed Central

    Fjellström, Ola; Akkaya, Sibel; Beisel, Hans-Georg; Eriksson, Per-Olof; Erixon, Karl; Gustafsson, David; Jurva, Ulrik; Kang, Daiwu; Karis, David; Knecht, Wolfgang; Nerme, Viveca; Nilsson, Ingemar; Olsson, Thomas; Redzic, Alma; Roth, Robert; Sandmark, Jenny; Tigerström, Anna; Öster, Linda

    2015-01-01

    Activated factor XI (FXIa) inhibitors are anticipated to combine anticoagulant and profibrinolytic effects with a low bleeding risk. This motivated a structure aided fragment based lead generation campaign to create novel FXIa inhibitor leads. A virtual screen, based on docking experiments, was performed to generate a FXIa targeted fragment library for an NMR screen that resulted in the identification of fragments binding in the FXIa S1 binding pocket. The neutral 6-chloro-3,4-dihydro-1H-quinolin-2-one and the weakly basic quinolin-2-amine structures are novel FXIa P1 fragments. The expansion of these fragments towards the FXIa prime side binding sites was aided by solving the X-ray structures of reported FXIa inhibitors that we found to bind in the S1-S1’-S2’ FXIa binding pockets. Combining the X-ray structure information from the identified S1 binding 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment and the S1-S1’-S2’ binding reference compounds enabled structure guided linking and expansion work to achieve one of the most potent and selective FXIa inhibitors reported to date, compound 13, with a FXIa IC50 of 1.0 nM. The hydrophilicity and large polar surface area of the potent S1-S1’-S2’ binding FXIa inhibitors compromised permeability. Initial work to expand the 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment towards the prime side to yield molecules with less hydrophilicity shows promise to afford potent, selective and orally bioavailable compounds. PMID:25629509

  20. Review of Operational Water Consumption and Withdrawal Factors for Electricity Generating Technologies

    SciTech Connect

    Macknick, J.; Newmark, R.; Heath, G.; Hallett, K. C.

    2011-03-01

    Various studies have attempted to consolidate published estimates of water use impacts of electricity generating technologies, resulting in a wide range of technologies and values based on different primary sources of literature. The goal of this work is to consolidate the various primary literature estimates of water use during the generation of electricity by conventional and renewable electricity generating technologies in the United States to more completely convey the variability and uncertainty associated with water use in electricity generating technologies.

  1. Childrearing Orientations in Mexican American Families: The Influence of Generation and Sociocultural Factors.

    ERIC Educational Resources Information Center

    Bureil, Raymond

    1993-01-01

    Compared childrearing practices used by Mexican-American parents of first-, second-, and third-generation adolescents. Findings from 317 parents revealed significant generational differences in childrearing styles. Parents of first- and second-generation adolescents reported more responsibility-oriented childrearing style, whereas parents of…

  2. Factors determining the precision of the correlated firing generated by a monosynaptic connection in the cat visual pathway

    PubMed Central

    Veredas, Francisco J; Vico, Francisco J; Alonso, Jose-Manuel

    2005-01-01

    Across the visual pathway, strong monosynaptic connections generate a precise correlated firing between presynaptic and postsynaptic neurons. The precision of this correlated firing is not the same within thalamus and visual cortex. While retinogeniculate connections generate a very narrow peak in the correlogram (peak width < 1 ms), the peaks generated by geniculocortical and corticocortical connections have usually a time course of several milliseconds. Several factors could explain these differences in timing precision such as the amplitude of the monosynaptic EPSP (excitatory postsynaptic potential), its time course or the contribution of polysynaptic inputs. While it is difficult to isolate the contribution of each factor in physiological experiments, a first approximation can be done in modelling studies. Here, we simulated two monosynaptically connected neurons to measure changes in their correlated firing as we independently modified different parameters of the connection. Our results suggest that the precision of the correlated firing generated by strong monosynaptic connections is mostly determined by the EPSP time course of the connection and much less by other factors. In addition, we show that a polysynaptic pathway is unlikely to emulate the correlated firing generated by a monosynaptic connection unless it generates EPSPs with very small latency jitter. PMID:16020458

  3. Universal risk factors for multifactorial diseases: LifeLines: a three-generation population-based study.

    PubMed

    Stolk, Ronald P; Rosmalen, Judith G M; Postma, Dirkje S; de Boer, Rudolf A; Navis, Gerjan; Slaets, Joris P J; Ormel, Johan; Wolffenbuttel, Bruce H R

    2008-01-01

    The risk for multifactorial diseases is determined by risk factors that frequently apply across disorders (universal risk factors). To investigate unresolved issues on etiology of and individual's susceptibility to multifactorial diseases, research focus should shift from single determinant-outcome relations to effect modification of universal risk factors. We present a model to investigate universal risk factors of multifactorial diseases, based on a single risk factor, a single outcome measure, and several effect modifiers. Outcome measures can be disease overriding, such as clustering of disease, frailty and quality of life. "Life course epidemiology" can be considered as a specific application of the proposed model, since risk factors and effect modifiers of multifactorial diseases typically have a chronic aspect. Risk factors are categorized into genetic, environmental, or complex factors, the latter resulting from interactions between (multiple) genetic and environmental factors (an example of a complex factor is overweight). The proposed research model of multifactorial diseases assumes that determinant-outcome relations differ between individuals because of modifiers, which can be divided into three categories. First, risk-factor modifiers that determine the effect of the determinant (such as factors that modify gene-expression in case of a genetic determinant). Second, outcome modifiers that determine the expression of the studied outcome (such as medication use). Third, generic modifiers that determine the susceptibility for multifactorial diseases (such as age). A study to assess disease risk during life requires phenotype and outcome measurements in multiple generations with a long-term follow up. Multiple generations will also enable to separate genetic and environmental factors. Traditionally, representative individuals (probands) and their first-degree relatives have been included in this type of research. We put forward that a three-generation

  4. Application of the compatibility factor to the design of segmented and cascaded themoelectric generators

    NASA Technical Reports Server (NTRS)

    Snyder, G. J

    2004-01-01

    Using thermoelectric compatibility, efficient thermoelectric generators are rationally designed. With examples, compatible and incompatible systems are explained and materials proposed for targeted development.

  5. Dependent Personality Disorder: Comparing an Expert Generated and Empirically Derived Five-Factor Model Personality Disorder Count

    ERIC Educational Resources Information Center

    Miller, Joshua D.; Lynam, Donald R.

    2008-01-01

    Assessment of the "Diagnostic and Statistical Manual of Mental Disorders" (4th Ed.; "DSM-IV") personality disorders (PDs) using five-factor model (FFM) prototypes and counts has shown substantial promise, with a few exceptions. Miller, Reynolds, and Pilkonis suggested that the expert-generated FFM dependent prototype might be misspecified in…

  6. A Continuum of Persistence: Low-Income and First-Generation College Students' Perceptions of Critical Factors for Postsecondary Success

    ERIC Educational Resources Information Center

    Ganuza Hoaglund, Zoila M.

    2014-01-01

    The purpose of this study was to explore similarities and differences among low-income and first-generation (LIFG) students' perceptions of influential academic, psychosocial, and contextual factors that shaped their persistence at different stages at the postsecondary level. This study consisted of 29 LIFG students from a large, urban research…

  7. Factors Associated with College Students' Intentions to Vaccinate Their Daughters Against HPV: Protecting the Next Generation.

    PubMed

    Wilson, Kelly L; White, Alice; Rosen, Brittany L; Chiappone, Alethea; Pulczinski, Jairus C; Ory, Marcia G; Smith, Matthew Lee

    2016-10-01

    Human papillomavirus (HPV) is a contemporary public health concern because of its association with cervical cancer. Despite evidence about HPV vaccination benefits, debate surrounds whether or not to vaccinate American youth. While no nationwide mandate exists, understanding the behaviors and intentions of future parents may provide insight about our ability to protect the next generation of school-aged youth. The purposes of this study were to examine factors associated with unmarried college students' intentions to: (1) vaccinate their daughters against HPV and (2) give their daughters the choice about whether or not to be vaccinated. Data were analyzed from 1606 college students aged 18-26 using an internet-delivered questionnaire. Two binary logistic regression analyses were performed identifying predictor variables associated with participants' intentions when having daughters in the future to vaccinate them against HPV and whether or not they would let their daughters decide to get the vaccination. Relative to those who did not intend to vaccinate their daughters against HPV, participants who were female (OR 1.55, P = 0.018), sexually active (OR 1.62, P = 0.001), diagnosed with HPV (OR 2.64, P < 0.001), received a flu shot in the past 12 months (OR 1.63, P = 0.002), perceived the HPV vaccine to be safe (OR 1.19, P < 0.001), and supported HPV vaccination mandates for school-aged youth (OR 2.58, P < 0.001) were more likely to report intentions of vaccinating their daughters against HPV. Participants who were sexually active (OR 1.45, P = 0.002) and perceived the HPV vaccine to be safe (OR 1.05, P = 0.012) were more likely to report they would allow their daughters to choose whether to be vaccinated against HPV. Until HPV vaccination mandates are enacted, parental support of vaccines are among the most effective way of increasing vaccine uptake. Identifying HPV vaccination support among future parents has potential to inform parent vaccination

  8. Factors Associated with College Students' Intentions to Vaccinate Their Daughters Against HPV: Protecting the Next Generation.

    PubMed

    Wilson, Kelly L; White, Alice; Rosen, Brittany L; Chiappone, Alethea; Pulczinski, Jairus C; Ory, Marcia G; Smith, Matthew Lee

    2016-10-01

    Human papillomavirus (HPV) is a contemporary public health concern because of its association with cervical cancer. Despite evidence about HPV vaccination benefits, debate surrounds whether or not to vaccinate American youth. While no nationwide mandate exists, understanding the behaviors and intentions of future parents may provide insight about our ability to protect the next generation of school-aged youth. The purposes of this study were to examine factors associated with unmarried college students' intentions to: (1) vaccinate their daughters against HPV and (2) give their daughters the choice about whether or not to be vaccinated. Data were analyzed from 1606 college students aged 18-26 using an internet-delivered questionnaire. Two binary logistic regression analyses were performed identifying predictor variables associated with participants' intentions when having daughters in the future to vaccinate them against HPV and whether or not they would let their daughters decide to get the vaccination. Relative to those who did not intend to vaccinate their daughters against HPV, participants who were female (OR 1.55, P = 0.018), sexually active (OR 1.62, P = 0.001), diagnosed with HPV (OR 2.64, P < 0.001), received a flu shot in the past 12 months (OR 1.63, P = 0.002), perceived the HPV vaccine to be safe (OR 1.19, P < 0.001), and supported HPV vaccination mandates for school-aged youth (OR 2.58, P < 0.001) were more likely to report intentions of vaccinating their daughters against HPV. Participants who were sexually active (OR 1.45, P = 0.002) and perceived the HPV vaccine to be safe (OR 1.05, P = 0.012) were more likely to report they would allow their daughters to choose whether to be vaccinated against HPV. Until HPV vaccination mandates are enacted, parental support of vaccines are among the most effective way of increasing vaccine uptake. Identifying HPV vaccination support among future parents has potential to inform parent vaccination

  9. Wind Power predictability a risk factor in the design, construction and operation of Wind Generation Turbines

    NASA Astrophysics Data System (ADS)

    Thiesen, J.; Gulstad, L.; Ristic, I.; Maric, T.

    2010-09-01

    Summit: The wind power predictability is often a forgotten decision and planning factor for most major wind parks, both onshore and offshore. The results of the predictability are presented after having examined a number of European offshore and offshore parks power predictability by using three(3) mesoscale model IRIE_GFS and IRIE_EC and WRF. Full description: It is well known that the potential wind production is changing with latitude and complexity in terrain, but how big are the changes in the predictability and the economic impacts on a project? The concept of meteorological predictability has hitherto to some degree been neglected as a risk factor in the design, construction and operation of wind power plants. Wind power plants are generally built in places where the wind resources are high, but these are often also sites where the predictability of the wind and other weather parameters is comparatively low. This presentation addresses the question of whether higher predictability can outweigh lower average wind speeds with regard to the overall economy of a wind power project. Low predictability also tends to reduce the value of the energy produced. If it is difficult to forecast the wind on a site, it will also be difficult to predict the power production. This, in turn, leads to increased balance costs and a less reduced carbon emission from the renewable source. By investigating the output from three(3) mesoscale models IRIE and WRF, using ECMWF and GFS as boundary data over a forecasting period of 3 months for 25 offshore and onshore wind parks in Europe, the predictability are mapped. Three operational mesoscale models with two different boundary data have been chosen in order to eliminate the uncertainty with one mesoscale model. All mesoscale models are running in a 10 km horizontal resolution. The model output are converted into "day a head" wind turbine generation forecasts by using a well proven advanced physical wind power model. The power models

  10. Factor XIa and Thrombin Generation Are Elevated in Patients with Acute Coronary Syndrome and Predict Recurrent Cardiovascular Events

    PubMed Central

    Loeffen, Rinske; van Oerle, René; Leers, Mathie P. G.; Kragten, Johannes A.; Crijns, Harry; Spronk, Henri M. H.; ten Cate, Hugo

    2016-01-01

    Objective In acute coronary syndrome (ACS) cardiac cell damage is preceded by thrombosis. Therefore, plasma coagulation markers may have additional diagnostic relevance in ACS. By using novel coagulation assays this study aims to gain more insight into the relationship between the coagulation system and ACS. Methods We measured plasma thrombin generation, factor XIa and D-dimer levels in plasma from ACS (n = 104) and non-ACS patients (n = 42). Follow-up measurements (n = 73) were performed at 1 and 6 months. Associations between coagulation markers and recurrent cardiovascular events were calculated by logistic regression analysis. Results Thrombin generation was significantly enhanced in ACS compared to non-ACS patients: peak height 148±53 vs. 122±42 nM. There was a significantly diminished ETP reduction (32 vs. 41%) and increased intrinsic coagulation activation (25 vs. 7%) in ACS compared to non-ACS patients. Furthermore, compared to non-ACS patients factor XIa and D-dimer levels were significantly elevated in ACS patients: 1.9±1.1 vs. 1.4±0.7 pM and 495(310–885) vs. 380(235–540) μg/L. Within the ACS spectrum, ST-elevated myocardial infarction patients had the highest prothrombotic profile. During the acute event, thrombin generation was significantly increased compared to 1 and 6 months afterwards: peak height 145±52 vs. 100±44 vs. 98±33 nM. Both peak height and factor XIa levels on admission predicted recurrent cardiovascular events (OR: 4.9 [95%CI 1.2–20.9] and 4.5 [1.1–18.9]). Conclusion ACS patients had an enhanced prothrombotic profile, demonstrated by an increased thrombin generation potential, factor XIa and D-dimer levels. This study is the first to demonstrate the positive association between factor XIa, thrombin generation and recurrent cardiovascular events. PMID:27419389

  11. Updated greenhouse gas and criteria air pollutant emission factors and their probability distribution functions for electricity generating units

    SciTech Connect

    Cai, H.; Wang, M.; Elgowainy, A.; Han, J.

    2012-07-06

    Greenhouse gas (CO{sub 2}, CH{sub 4} and N{sub 2}O, hereinafter GHG) and criteria air pollutant (CO, NO{sub x}, VOC, PM{sub 10}, PM{sub 2.5} and SO{sub x}, hereinafter CAP) emission factors for various types of power plants burning various fuels with different technologies are important upstream parameters for estimating life-cycle emissions associated with alternative vehicle/fuel systems in the transportation sector, especially electric vehicles. The emission factors are typically expressed in grams of GHG or CAP per kWh of electricity generated by a specific power generation technology. This document describes our approach for updating and expanding GHG and CAP emission factors in the GREET (Greenhouse Gases, Regulated Emissions, and Energy Use in Transportation) model developed at Argonne National Laboratory (see Wang 1999 and the GREET website at http://greet.es.anl.gov/main) for various power generation technologies. These GHG and CAP emissions are used to estimate the impact of electricity use by stationary and transportation applications on their fuel-cycle emissions. The electricity generation mixes and the fuel shares attributable to various combustion technologies at the national, regional and state levels are also updated in this document. The energy conversion efficiencies of electric generating units (EGUs) by fuel type and combustion technology are calculated on the basis of the lower heating values of each fuel, to be consistent with the basis used in GREET for transportation fuels. On the basis of the updated GHG and CAP emission factors and energy efficiencies of EGUs, the probability distribution functions (PDFs), which are functions that describe the relative likelihood for the emission factors and energy efficiencies as random variables to take on a given value by the integral of their own probability distributions, are updated using best-fit statistical curves to characterize the uncertainties associated with GHG and CAP emissions in life

  12. Fc gamma receptor IIIb enhances Fc gamma receptor IIa function in an oxidant-dependent and allele-sensitive manner.

    PubMed Central

    Salmon, J E; Millard, S S; Brogle, N L; Kimberly, R P

    1995-01-01

    Two classes of receptors for IgG, Fc gamma RIIa and Fc gamma RIIIb, both of which exist in two allelic forms, are expressed on human neutrophils. Neutrophils from normal donors, homozygous for the different allelic phenotypes of Fc gamma RIIIb, have significantly different levels of Fc gamma receptor-mediated phagocytosis of IgG-opsonized erythrocytes (EA). However, the observation that Fc gamma RIIIb mediates phagocytosis of specific mAb-targeted erythrocytes poorly suggests that this receptor may influence EA internalization by Fc gamma RIIa in an allele-sensitive fashion. Donors homozygous for the NA1 allele of Fc gamma RIIIb showed greater activation of Fc gamma RIIa after Fc gamma RIIIb cross-linking than donors homozygous for the NA2 allele of Fc gamma RIIIb. This increase in receptor-specific internalization reflects both an increase in ligand binding by Fc gamma RIIa and an increase in internalization efficiency of targets bound. Activation of Fc gamma RIIa by Fc gamma RIIIb is transferable by supernatants from activated cells and is blocked by inhibitors of reactive oxygen species and the H2O2-myeloperoxidase-chloride system and by serine protease inhibitors. Thus, cross-linking of Fc gamma RIIIb, which leads to neutrophil degranulation and the generation of reactive oxygen intermediates, in turn alters Fc gamma RIIa avidity and efficiency. These oxidant-mediated changes in Fc gamma RIIa function provide a novel mechanism for receptors to collaborate in both an autocrine and paracrine fashion. The allele sensitivity of these effects suggests that Fc gamma receptor polymorphisms may be inherited disease susceptibility factors in host defense against infection and in the development of autoimmunity. Images PMID:7769129

  13. A novel sensitive assay for functional factor XII based on the generation of kallikrein-C1-inhibitor complexes in factor XII-deficient plasma by glass-bound factor XII.

    PubMed

    Dors, D M; Nuijens, J H; Huijbregts, C C; Hack, C E

    1992-06-01

    We developed a very sensitive assay for functional factor XII. This assay is based on the property of glass-bound factor XII to activate prekallikrein (PK) into kallikrein in factor XII-deficient plasma, which is assessed by measuring the formation of kallikrein-C1-inhibitor complexes in this plasma by radioimmunoassay. Incubation of varying amounts of factor XII in glass tubes led to a dose-dependent increase in kallikrein-C1-inhibitor complexes in factor XII-deficient plasma with a lower limit of detection of +/- 20 pg of factor XII. The specificity of the assay for factor XII was demonstrated by experiments with plasmas deficient for factor XII, PK or high molecular weight kininogen (HK) and by incubation of factor XII with Polybrene or with a monoclonal antibody that inhibits the amidolytic and procoagulant activity of factor XII. The high sensitivity of the assay appeared to be due to the inability of C1-inhibitor to inhibit factor XII bound to glass, which resulted in a molar ratio of generated kallikrein to glass-bound factor XII of at least 100:1. This assay for factor XII may be a feasible tool in studies on structural and functional aspects of (recombinant) factor XII species synthesized by cultured cells.

  14. [Locally advanced carcinoma of the cervix uteri (stage IIB-IIIB TNM-UICC): radiotherapy combined with simultaneous daily low-dose platinum. Phase II study].

    PubMed

    Micheletti, E; La Face, B; Bianchi, E; Cagna, E; Sartori, E

    1996-05-01

    A prospective, single arm, phase-II trial was performed to assess the efficacy and local toxicity of the combination of low doses of platin and pelvic radiotherapy in patients with locally advanced carcinoma of the cervix. January, 1993, through August, 1994, twenty-three previously untreated patients with squamous carcinoma (stages IIB-IIIB UICC) entered the study. All patients were examined by a gynecologist and by a radiation oncologist and then submitted to conventional pretreatment staging procedures. Nine patients were classified as stage IIB and 14 patients as stage IIIB. Radiotherapy consisted of 60 Gy external beam irradiation (46 Gy to pelvis + 14 Gy boost to cervix uteri and parametria) plus one low dose rate intracavitary treatment to a dose of 8 Gy to point A. Cisplatin (3 mg/m2/day) or carboplatin (12 mg/m2/day) was also given for 6 weeks starting on radiotherapy day 1. The treatment was well tolerated and no patient required radiotherapy discontinuation. With a median follow-up time of 20 months, complete response was seen in 74% (17/23) of the patients. One of the 17 patients who achieved a complete remission, during follow-up, relapsed in the pelvis and one developed lung metastases. Total failure rate in the pelvis was 30.5% (7/23). Distant metastases were observed in 17.5% (4/23) of the patients. Actuarial overall and disease-free survival rates at 33 months were 69.1% and 65.2%, respectively. Late gastrointestinal toxicity (grade 3) occurred in 8.6% (2/23) of patients, with one patient developing a rectal ulcer-which was submitted to colostomy- and one patient a vaginal necrosis. The combination of platin and radiotherapy appears to be an effective regimen for the patients with locally advanced carcinoma of the cervix and caused a relatively low rate of late gastrointestinal complications.

  15. 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

  16. Generation of enhanced stability factor VIII variants by replacement of charged residues at the A2 domain interface.

    PubMed

    Wakabayashi, Hironao; Varfaj, Fatbardha; Deangelis, Jennifer; Fay, Philip J

    2008-10-01

    Factor VIII consists of a heavy chain (A1A2B domains) and light chain (A3C1C2 domains), whereas the contiguous A1A2 domains are separate subunits in the cofactor, factor VIIIa. The intrinsic instability of the cofactor results from weak affinity interactions of the A2 subunit within factor VIIIa. The charged residues Glu272, Asp519, Glu665, and Glu1984 appear buried at the interface of the A2 domain with either the A1 or A3 domain, and thus may impact protein stability. To determine the effects of these residues on procofactor/cofactor stability, these residues were individually replaced with either Ala or Val, and stable BHK cell lines expressing the B-domainless proteins were prepared. Specific activity and thrombin generation parameters for 7 of the 8 variants were more than 80% the wild-type value. Factor VIII activity at 52 degrees C to 60 degrees C and the decay of factor VIIIa activity after thrombin activation were monitored. Six of the 7 variants showing wild-type-like activity demonstrated enhanced stability, with the Glu1984Val variant showing a 2-fold increase in thermostability and an approximately 4- to 8-fold increase in stability of factor VIIIa. These results indicate that replacement of buried charged residues is an effective alternative to covalent modification in increasing factor VIII (VIIIa) stability. PMID:18650448

  17. Contextual Factors Contributing to Ethnic Identity Development of Second-Generation Iranian American Adolescents

    ERIC Educational Resources Information Center

    Daha, Maryam

    2011-01-01

    The data drawn from interviews with 55 second-generation Iranian American adolescents revealed that pride in ancient Persian culture, the adolescents' physical characteristics, perceived stereotypes, and community point of reference all combined to affect ethnic identity as well as to reinforce a sense of ethnic loyalty. The contextual factors…

  18. Self-Generated Goals and Goal Process Appraisals: Relationships with Sociodemographic Factors and Well-Being

    ERIC Educational Resources Information Center

    Massey, Emma K.; Gebhardt, Winifred A.; Garnefski, Nadia

    2009-01-01

    In this study the full array of personal goals pursued by adolescents was examined using an idiographic goal-elicitation procedure. The aims of the study were twofold. Firstly, we investigated individual differences in self-generated goals and goal process appraisals based on sociodemographic characteristics. Secondly, we investigated the…

  19. First-Generation Freshman College Students: Factors Impacting Retention for the Subsequent Year

    ERIC Educational Resources Information Center

    McLean, Laura Colson

    2013-01-01

    Against all odds, first-generation college students continue to enroll in postsecondary schools with aspirations of obtaining a bachelor's degree. Unfortunately, many have not successfully reached their goal, which in turn has affected retention rates of colleges and universities. There are programs that provide academic support and advising to…

  20. [Electrode configuration as a factor affecting electricity generation in air-cathode microbial fuel cell].

    PubMed

    You, Shi-Jie; Zhao, Qing-Liang; Jiang, Jun-Qiu

    2006-11-01

    In air-cathode microbial fuel cell (ACMFC), oxygen diffused into the reactor from cathode without PEM can be reduced as electron acceptor via aerobic respiration by facultative microorganisms, resulting in either a decreasing of power generation or electron loss. In this study, ACMFC1 and ACMFC2 with different electrode configuration were compared to examine power density and electron recovery from glucose. The results showed that ACMFC1 generated a maximum power density of 3 070mW/m3 with internal resistance of 302.141 and anode potential of -323mV; while maximum power density of 9 800mW/m3 for ACMFC2 was obtained with internal resistance of 107.79omega and anode potential of -442mV. ACMFC2 could sustain generating electricity for nearly 220 h (ERE of 30.1%), comparing with ACMFC1 of less than 50 h (ERE of 9.78%) under batch operation. Therefore, an improved design for electrode configuration of ACMFC can be performed to generate higher power with low internal resistance, meanwhile, achieve increasing electron recovery simultaneously.

  1. Viewing Generativity and Social Capital as Underlying Factors of Parent Involvement

    ERIC Educational Resources Information Center

    Stevens, Sharon; Patel, Nimisha

    2015-01-01

    Parent involvement in education is a multifaceted support that has many well-documented benefits for students of all ages. Parent involvement is also a common expression of generativity as defined in Erik Erikson's theory of psychosocial development. The activities parents engage in during their children's educational pursuits, as well as their…

  2. Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in DICER1 syndrome: a unique variant of the two-hit tumor suppression model.

    PubMed

    Brenneman, Mark; Field, Amanda; Yang, Jiandong; Williams, Gretchen; Doros, Leslie; Rossi, Christopher; Schultz, Kris Ann; Rosenberg, Avi; Ivanovich, Jennifer; Turner, Joyce; Gordish-Dressman, Heather; Stewart, Douglas; Yu, Weiying; Harris, Anne; Schoettler, Peter; Goodfellow, Paul; Dehner, Louis; Messinger, Yoav; Hill, D Ashley

    2015-01-01

    Pleuropulmonary blastoma (PPB) is the most frequent pediatric lung tumor and often the first indication of a pleiotropic cancer predisposition,  DICER1 syndrome, comprising a range of other individually rare, benign and malignant tumors of childhood and early adulthood. The genetics of  DICER1-associated tumorigenesis are unusual in that tumors typically bear neomorphic missense mutations at one of five specific "hotspot" codons within the RNase IIIb domain of  DICER 1, combined with complete loss of function (LOF) in the other allele. We analyzed a cohort of 124 PPB children for predisposing  DICER1 mutations and sought correlations with clinical phenotypes. Over 70% have inherited or  de novo germline LOF mutations, most of which truncate the  DICER1 open reading frame. We identified a minority of patients who have no germline mutation, but are instead mosaic for predisposing  DICER1 mutations. Mosaicism for RNase IIIb domain hotspot mutations defines a special category of  DICER1 syndrome patients, clinically distinguished from those with germline or mosaic LOF mutations by earlier onsets and numerous discrete foci of neoplastic disease involving multiple syndromic organ sites. A final category of patients lack predisposing germline or mosaic mutations and have disease limited to a single PPB tumor bearing tumor-specific RNase IIIb and LOF mutations. We propose that acquisition of a neomorphic RNase IIIb domain mutation is the rate limiting event in  DICER1-associated  tumorigenesis, and that distinct clinical phenotypes associated with mutational categories reflect the temporal order in which LOF and RNase IIIb domain mutations are acquired during development.

  3. Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in DICER1 syndrome: a unique variant of the two-hit tumor suppression model.

    PubMed

    Brenneman, Mark; Field, Amanda; Yang, Jiandong; Williams, Gretchen; Doros, Leslie; Rossi, Christopher; Schultz, Kris Ann; Rosenberg, Avi; Ivanovich, Jennifer; Turner, Joyce; Gordish-Dressman, Heather; Stewart, Douglas; Yu, Weiying; Harris, Anne; Schoettler, Peter; Goodfellow, Paul; Dehner, Louis; Messinger, Yoav; Hill, D Ashley

    2015-01-01

    Pleuropulmonary blastoma (PPB) is the most frequent pediatric lung tumor and often the first indication of a pleiotropic cancer predisposition,  DICER1 syndrome, comprising a range of other individually rare, benign and malignant tumors of childhood and early adulthood. The genetics of  DICER1-associated tumorigenesis are unusual in that tumors typically bear neomorphic missense mutations at one of five specific "hotspot" codons within the RNase IIIb domain of  DICER 1, combined with complete loss of function (LOF) in the other allele. We analyzed a cohort of 124 PPB children for predisposing  DICER1 mutations and sought correlations with clinical phenotypes. Over 70% have inherited or  de novo germline LOF mutations, most of which truncate the  DICER1 open reading frame. We identified a minority of patients who have no germline mutation, but are instead mosaic for predisposing  DICER1 mutations. Mosaicism for RNase IIIb domain hotspot mutations defines a special category of  DICER1 syndrome patients, clinically distinguished from those with germline or mosaic LOF mutations by earlier onsets and numerous discrete foci of neoplastic disease involving multiple syndromic organ sites. A final category of patients lack predisposing germline or mosaic mutations and have disease limited to a single PPB tumor bearing tumor-specific RNase IIIb and LOF mutations. We propose that acquisition of a neomorphic RNase IIIb domain mutation is the rate limiting event in  DICER1-associated  tumorigenesis, and that distinct clinical phenotypes associated with mutational categories reflect the temporal order in which LOF and RNase IIIb domain mutations are acquired during development. PMID:26925222

  4. Concurrent Phosphorus Recovery and Energy Generation in Mediator-Less Dual Chamber Microbial Fuel Cells: Mechanisms and Influencing Factors.

    PubMed

    Almatouq, Abdullah; Babatunde, Akintunde O

    2016-03-29

    This study investigated the mechanism and key factors influencing concurrent phosphorus (P) recovery and energy generation in microbial fuel cells (MFC) during wastewater treatment. Using a mediator-less dual chamber microbial fuel cell operated for 120 days; P was shown to precipitate as struvite when ammonium and magnesium chloride solutions were added to the cathode chamber. Monitoring data for chemical oxygen demand (COD), pH, oxidation reduction potential (ORP) and aeration flow rate showed that a maximum 38% P recovery was achieved; and this corresponds to 1.5 g/L, pH > 8, -550 ± 10 mV and 50 mL/min respectively, for COD, pH(cathode), ORP and cathode aeration flow rate. More importantly, COD and aeration flow rate were shown to be the key influencing factors for the P recovery and energy generation. Results further show that the maximum P recovery corresponds to 72 mW/m² power density. However, the energy generated at maximum P recovery was not the optimum; this shows that whilst P recovery and energy generation can be concurrently achieved in a microbial fuel cell, neither can be at the optimal value.

  5. Concurrent Phosphorus Recovery and Energy Generation in Mediator-Less Dual Chamber Microbial Fuel Cells: Mechanisms and Influencing Factors

    PubMed Central

    Almatouq, Abdullah; Babatunde, Akintunde O.

    2016-01-01

    This study investigated the mechanism and key factors influencing concurrent phosphorus (P) recovery and energy generation in microbial fuel cells (MFC) during wastewater treatment. Using a mediator-less dual chamber microbial fuel cell operated for 120 days; P was shown to precipitate as struvite when ammonium and magnesium chloride solutions were added to the cathode chamber. Monitoring data for chemical oxygen demand (COD), pH, oxidation reduction potential (ORP) and aeration flow rate showed that a maximum 38% P recovery was achieved; and this corresponds to 1.5 g/L, pH > 8, −550 ± 10 mV and 50 mL/min respectively, for COD, pHcathode, ORP and cathode aeration flow rate. More importantly, COD and aeration flow rate were shown to be the key influencing factors for the P recovery and energy generation. Results further show that the maximum P recovery corresponds to 72 mW/m2 power density. However, the energy generated at maximum P recovery was not the optimum; this shows that whilst P recovery and energy generation can be concurrently achieved in a microbial fuel cell, neither can be at the optimal value. PMID:27043584

  6. Factors affecting eluation characteristics of sorption generators of technetium-99m

    NASA Astrophysics Data System (ADS)

    Skuridin, V. S.; Chernov, V. I.; Sadkin, V. L.; Stasyuk, E. S.; Varlamova, N. V.; Rogov, A. S.; Nesterov, E. A.; Ilina, E. A.; Larionova, L. A.; Medvedeva, A. A.

    2016-08-01

    The influence of the adsorbed mass of molybdenum on the width of eluation profiles of generators and the patterns of molybdenum distribution in the amount of chromatographic columns by scanning them on the germanium-gallium detector using collimating device are studied. The boundary conditions under which the maximum value of 99mTc yield from generators Ye = 1 are defined. After scanning the columns, it was found out that the degree of filling the columns with molybdenum Q and the value of its maximum adsorption depend naturally on the total weight of the adsorbed mass. In order to achieve the condition Ye = 1 the value of Q should be at least 85%.

  7. Generation of embryos directly from embryonic stem cells by tetraploid embryo complementation reveals a role for GATA factors in organogenesis.

    PubMed

    Duncan, S A

    2005-12-01

    Gene targeting in ES (embryonic stem) cells has been used extensively to study the role of proteins during embryonic development. In the traditional procedure, this requires the generation of chimaeric mice by introducing ES cells into blastocysts and allowing them to develop to term. Once chimaeric mice are produced, they are bred into a recipient mouse strain to establish germline transmission of the allele of interest. Although this approach has been used very successfully, the breeding cycles involved are time consuming. In addition, genes that are essential for organogenesis often have roles in the formation of extra-embryonic tissues that are essential for early stages of post-implantation development. For example, mice lacking the GATA transcription factors, GATA4 or GATA6, arrest during gastrulation due to an essential role for these factors in differentiation of extra-embryonic endoderm. This lethality has frustrated the study of these factors during the development of organs such as the liver and heart. Extraembryonic defects can, however, be circumvented by generating clonal mouse embryos directly from ES cells by tetraploid complementation. Here, we describe the usefulness and efficacy of this approach using GATA factors as an example.

  8. Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

    SciTech Connect

    Prueksaritanont, Thomayant . E-mail: thomayant_prueksaritanont@merck.com; Lin, Jiunn H.; Baillie, Thomas A.

    2006-12-01

    This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models.

  9. Key Motivational Factors in the Retention of Three Generations of Public High School Mathematics Teachers

    ERIC Educational Resources Information Center

    Pospichal, Wendy

    2011-01-01

    Purpose: The purpose of this study was to describe and compare the similarities and differences between five key motivational factors: (a) new teacher induction, (b) noninduction mentor support in the early years of teaching, (c) salary and benefits, (d) working conditions, and (e) administrative support influential in retention of employment in…

  10. Perceived Factors Influencing the Pursuit of Higher Education among First-Generation College Students

    ERIC Educational Resources Information Center

    Coy-Ogan, Lynne

    2009-01-01

    Students who are first in their families to pursue higher education are often less likely to receive the academic, social, and financial support needed to experience success when compared to students from college-educated families. This study examined the perceived differences among salient factors influencing the pursuit of higher education…

  11. Investigating the "g"-Saturation of Various Stratum-Two Factors Using Automatic Item Generation

    ERIC Educational Resources Information Center

    Arendasy, Martin E.; Hergovich, Andreas; Sommer, Markus

    2008-01-01

    Even though researchers agree on the hierarchical structure of intelligence there is considerable disagreement on the g-saturation of the lower stratum-two factors. In this article it is argued that the mixed evidence in the research literature can be at least partially attributed to the construct representation of the individual tests used to…

  12. Environmental and sustainability factors associated with next-generation biofuels in the U.S.: what do we really know?

    PubMed

    Williams, Pamela R D; Inman, Daniel; Aden, Andy; Heath, Garvin A

    2009-07-01

    In this paper, we assess what is known or anticipated about environmental and sustainability factors associated with next-generation biofuels relative to the primary conventional biofuels (i.e., corn grain-based ethanol and soybean-based diesel) in the United States during feedstock production and conversion processes. Factors considered include greenhouse (GHG) emissions, air pollutant emissions, soil health and quality, water use and water quality, wastewater and solid waste streams, and biodiversity and land-use changes. Based on our review of the available literature, we find that the production of next-generation feedstocks in the U.S. (e.g., municipal solid waste, forest residues, dedicated energy crops, microalgae) are expected to fare better than corn-grain or soybean production on most of these factors, although the magnitude of these differences may vary significantly among feedstocks. Ethanol produced using a biochemical or thermochemical conversion platform is expected to result in fewer GHG and air pollutant emissions, but to have similar or potentially greater water demands and solid waste streams than conventional ethanol biorefineries in the U.S. However, these conversion-related differences are likely to be small, particularly relative to those associated with feedstock production. Modeling performed for illustrative purposes and to allow for standardized quantitative comparisons across feedstocks and conversion technologies generally confirms the findings from the literature. Despite current expectations, significant uncertainty remains regarding how well next-generation biofuels will fare on different environmental and sustainability factors when produced on a commercial scale in the U.S. Additional research is needed in several broad areas including quantifying impacts, designing standardized metrics and approaches, and developing decision-support tools to identify and quantify environmental trade-offs and ensure sustainable biofuels production.

  13. State-level Greenhouse Gas Emission Factors for Electricity Generation, Updated

    EIA Publications

    2001-01-01

    To assist reporters in estimating emissions and emission reductions, The Energy Information Administration (EIA) has made available in the instructions to Forms EIA-1605 and EIA-1605EZ emission coefficients for most commonly used fossil fuels and electricity. These coefficients were based on 1992 emissions and generation data. In 1999, updated coefficients were prepared based on the most recent data (1998) then available; however, the updated coefficients were not included in the instructions for the 1999 data year. This year, they have been updated again, but based on three years worth of data (1997, 1998, and 1999) rather than a single year.

  14. TRANSCRIPTION FACTOR Bmsage PLAYS A CRUCIAL ROLE IN SILK GLAND GENERATION IN SILKWORM, Bombyx mori.

    PubMed

    Xin, Hu-hu; Zhang, Deng-pan; Chen, Rui-ting; Cai, Zi-zheng; Lu, Yan; Liang, Shuang; Miao, Yun-gen

    2015-10-01

    Salivary gland secretion is altered in Drosophila embryos with loss of function of the sage gene. Saliva has a reduced volume and an increased electron density according to transmission electron microscopy, resulting in regions of tube dilation and constriction with intermittent tube closure. However, the precise functions of Bmsage in silkworm (Bombyx mori) are unknown, although its sequence had been deposited in SilkDB. From this, Bmsage is inferred to be a transcription factor that regulates the synthesis of silk fibroin and interacts with another silk gland-specific transcription factor, namely, silk gland factor-1. In this study, we introduced a germline mutation of Bmsage using the Cas9/sgRNA system, a genome-editing technology, resulting in deletion of Bmsage from the genome of B. mori. Of the 15 tested samples, seven displayed alterations at the target site. The mutagenesis efficiency was about 46.7% and there were no obvious off-target effects. In the screened homozygous mutants, silk glands developed poorly and the middle and posterior silk glands (MSG and PSG) were absent, which was significantly different from the wild type. The offspring of G0 mosaic silkworms had indel mutations causing 2- or 9-bp deletions at the target site, but exhibited the same abnormal silk gland structure. Mutant larvae containing different open-reading frames of Bmsage had the same silk gland phenotype. This illustrated that the mutant phenotype was due to Bmsage knockout. We conclude that Bmsage participates in embryonic development of the silk gland.

  15. Generation of in vivo activating factors in the ischemic intestine by pancreatic enzymes

    NASA Astrophysics Data System (ADS)

    Mitsuoka, Hiroshi; Kistler, Erik B.; Schmid-Schönbein, Geert W.

    2000-02-01

    One of the early events in physiological shock is the generation of activators for leukocytes, endothelial cells, and other cells in the cardiovascular system. The mechanism by which these activators are produced has remained unresolved. We examine here the hypothesis that pancreatic digestive enzymes in the ischemic intestine may be involved in the generation of activators during intestinal ischemia. The lumen of the small intestine of rats was continuously perfused with saline containing a broadly acting pancreatic enzyme inhibitor (6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfate, 0.37 mM) before and during ischemia of the small intestine by splanchnic artery occlusion. This procedure inhibited activation of circulating leukocytes during occlusion and reperfusion. It also prevented the appearance of activators in portal venous and systemic artery plasma and attenuated initiating symptoms of multiple organ injury in shock. Intestinal tissue produces only low levels of activators in the absence of pancreatic enzymes, whereas in the presence of enzymes, activators are produced in a concentration- and time-dependent fashion. The results indicate that pancreatic digestive enzymes in the ischemic intestine serve as an important source for cell activation and inflammation, as well as multiple organ failure.

  16. TRANSCRIPTION FACTOR Bmsage PLAYS A CRUCIAL ROLE IN SILK GLAND GENERATION IN SILKWORM, Bombyx mori.

    PubMed

    Xin, Hu-hu; Zhang, Deng-pan; Chen, Rui-ting; Cai, Zi-zheng; Lu, Yan; Liang, Shuang; Miao, Yun-gen

    2015-10-01

    Salivary gland secretion is altered in Drosophila embryos with loss of function of the sage gene. Saliva has a reduced volume and an increased electron density according to transmission electron microscopy, resulting in regions of tube dilation and constriction with intermittent tube closure. However, the precise functions of Bmsage in silkworm (Bombyx mori) are unknown, although its sequence had been deposited in SilkDB. From this, Bmsage is inferred to be a transcription factor that regulates the synthesis of silk fibroin and interacts with another silk gland-specific transcription factor, namely, silk gland factor-1. In this study, we introduced a germline mutation of Bmsage using the Cas9/sgRNA system, a genome-editing technology, resulting in deletion of Bmsage from the genome of B. mori. Of the 15 tested samples, seven displayed alterations at the target site. The mutagenesis efficiency was about 46.7% and there were no obvious off-target effects. In the screened homozygous mutants, silk glands developed poorly and the middle and posterior silk glands (MSG and PSG) were absent, which was significantly different from the wild type. The offspring of G0 mosaic silkworms had indel mutations causing 2- or 9-bp deletions at the target site, but exhibited the same abnormal silk gland structure. Mutant larvae containing different open-reading frames of Bmsage had the same silk gland phenotype. This illustrated that the mutant phenotype was due to Bmsage knockout. We conclude that Bmsage participates in embryonic development of the silk gland. PMID:25917878

  17. The classical Darboux III oscillator: factorization, Spectrum Generating Algebra and solution to the equations of motion

    NASA Astrophysics Data System (ADS)

    Latini, D.; Ragnisco, O.; Ballesteros, A.; Enciso, A.; Herranz, F. J.; Riglioni, D.

    2016-01-01

    In a recent paper the so-called Spectrum Generating Algebra (SGA) technique has been applied to the N-dimensional Taub-NUT system, a maximally superintegrable Hamiltonian system which can be interpreted as a one-parameter deformation of the Kepler-Coulomb system. Such a Hamiltonian is associated to a specific Bertrand space of non-constant curvature. The SGA procedure unveils the symmetry algebra underlying the Hamiltonian system and, moreover, enables one to solve the equations of motion. Here we will follow the same path to tackle the Darboux III system, another maximally superintegrable system, which can indeed be viewed as a natural deformation of the isotropic harmonic oscillator where the flat Euclidean space is again replaced by another space of non-constant curvature.

  18. Source segregation of food waste in office areas: Factors affecting waste generation rates and quality.

    PubMed

    Edjabou, Maklawe Essonanawe; Boldrin, Alessio; Scheutz, Charlotte; Astrup, Thomas Fruergaard

    2015-12-01

    Existing legislation mandates that the amount of waste being recycled should be increased. Among others, in its Resource Strategy Plan, the Danish Government decided that at least 60% of food waste generated by the service sector, including in office areas, should be source-sorted and collected separately by 2018. To assess the achievability of these targets, source-sorted food waste and residual waste from office areas was collected and weighed on a daily basis during 133 working days. Waste composition analyses were conducted every week to investigate the efficiency of the source-sorting campaign and the purity of the source-sorted food waste. The moisture content of source-sorted food waste and residual waste fractions, and potential methane production from source-sorted food waste, was also investigated. Food waste generation equated to 23 ± 5 kg/employee/year, of which 20 ± 5 kg/employee/year was source-sorted, with a considerably high purity of 99%. Residual waste amounted to 10 ± 5 kg/employee/year and consisted mainly of paper (29 ± 13%), plastic (23 ± 9%) and missorted food waste (24 ± 16%). The moisture content of source-sorted food waste was significantly higher (8%) than missorted food waste, and the methane potential of source-sorted food waste was 463 ± 42 mL CH4/g VS. These results show that food waste in office areas offers promising potential for relatively easily collectable and pure source-sorted food waste, suggesting that recycling targets for food waste could be achieved with reasonable logistical ease in office areas.

  19. Source segregation of food waste in office areas: Factors affecting waste generation rates and quality.

    PubMed

    Edjabou, Maklawe Essonanawe; Boldrin, Alessio; Scheutz, Charlotte; Astrup, Thomas Fruergaard

    2015-12-01

    Existing legislation mandates that the amount of waste being recycled should be increased. Among others, in its Resource Strategy Plan, the Danish Government decided that at least 60% of food waste generated by the service sector, including in office areas, should be source-sorted and collected separately by 2018. To assess the achievability of these targets, source-sorted food waste and residual waste from office areas was collected and weighed on a daily basis during 133 working days. Waste composition analyses were conducted every week to investigate the efficiency of the source-sorting campaign and the purity of the source-sorted food waste. The moisture content of source-sorted food waste and residual waste fractions, and potential methane production from source-sorted food waste, was also investigated. Food waste generation equated to 23 ± 5 kg/employee/year, of which 20 ± 5 kg/employee/year was source-sorted, with a considerably high purity of 99%. Residual waste amounted to 10 ± 5 kg/employee/year and consisted mainly of paper (29 ± 13%), plastic (23 ± 9%) and missorted food waste (24 ± 16%). The moisture content of source-sorted food waste was significantly higher (8%) than missorted food waste, and the methane potential of source-sorted food waste was 463 ± 42 mL CH4/g VS. These results show that food waste in office areas offers promising potential for relatively easily collectable and pure source-sorted food waste, suggesting that recycling targets for food waste could be achieved with reasonable logistical ease in office areas. PMID:26260965

  20. The next generation of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of lung cancer.

    PubMed

    Steuer, Conor E; Khuri, Fadlo R; Ramalingam, Suresh S

    2015-04-15

    The discovery of "driver" genomic alterations in patients with non-small cell lung cancer (NSCLC) has dramatically changed the field of thoracic oncology in recent years. The best understood of these molecular drivers are those involving the epidermal growth factor receptor (EGFR), which when aberrantly activated are integral to the development of a subset of NSCLC tumors. First-generation and second-generation tyrosine kinase inhibitors (TKIs) specific to the activated EGFR have shown significant efficacy and have brought about the era of targeted therapy for NSCLC. The most common resistance mechanism is a threonine-to-methionine substitution (T790M) in exon 20 of the EGFR gene. Although the previous standard of care in patients with EGFR-mutated NSCLC that progressed on initial TKI therapy was chemotherapy, third-generation EGFR TKIs have now been developed and have yielded promising results for this population of patients with NSCLC. This article reviews the emerging data regarding third-generation agents in the treatment of patients with advanced NSCLC.

  1. The African Experience. Volume I: Syllabus Lectures; Volume II: Bibliographic References; Volume IIIA: Introductory Essays; Volume IIIB: Introductory Essays.

    ERIC Educational Resources Information Center

    Paden, John N.; Soja, Edward W.

    In response to demands for more and better teaching about Africa in American higher education, the US Office of Education requested that the Program of African Studies at Northwestern University generate a set of teaching materials which could be used in introductory undergraduate courses. Included in these volumes, these materials provide…

  2. Aberrant DNA methylation reprogramming during induced pluripotent stem cell generation is dependent on the choice of reprogramming factors.

    PubMed

    Planello, Aline C; Ji, Junfeng; Sharma, Vivek; Singhania, Rajat; Mbabaali, Faridah; Müller, Fabian; Alfaro, Javier A; Bock, Christoph; De Carvalho, Daniel D; Batada, Nizar N

    2014-01-01

    The conversion of somatic cells into pluripotent stem cells via overexpression of reprogramming factors involves epigenetic remodeling. DNA methylation at a significant proportion of CpG sites in induced pluripotent stem cells (iPSCs) differs from that of embryonic stem cells (ESCs). Whether different sets of reprogramming factors influence the type and extent of aberrant DNA methylation in iPSCs differently remains unknown. In order to help resolve this critical question, we generated human iPSCs from a common fibroblast cell source using either the Yamanaka factors (OCT4, SOX2, KLF4 and cMYC) or the Thomson factors (OCT4, SOX2, NANOG and LIN28), and determined their genome-wide DNA methylation profiles. In addition to shared DNA methylation aberrations present in all our iPSCs, we identified Yamanaka-iPSC (Y-iPSC)-specific and Thomson-iPSC (T-iPSC)-specific recurrent aberrations. Strikingly, not only were the genomic locations of the aberrations different but also their types: reprogramming with Yamanaka factors mainly resulted in failure to demethylate CpGs, whereas reprogramming with Thomson factors mainly resulted in failure to methylate CpGs. Differences in the level of transcripts encoding DNMT3b and TET3 between Y-iPSCs and T-iPSCs may contribute partially to the distinct types of aberrations. Finally, de novo aberrantly methylated genes in Y-iPSCs were enriched for NANOG targets that are also aberrantly methylated in some cancers. Our study thus reveals that the choice of reprogramming factors influences the amount, location, and class of DNA methylation aberrations in iPSCs. These findings may provide clues into how to produce human iPSCs with fewer DNA methylation abnormalities. PMID:25408883

  3. Non-viral generation of marmoset monkey iPS cells by a six-factor-in-one-vector approach.

    PubMed

    Debowski, Katharina; Warthemann, Rita; Lentes, Jana; Salinas-Riester, Gabriela; Dressel, Ralf; Langenstroth, Daniel; Gromoll, Jörg; Sasaki, Erika; Behr, Rüdiger

    2015-01-01

    Groundbreaking studies showed that differentiated somatic cells of mouse and human origin could be reverted to a stable pluripotent state by the ectopic expression of only four proteins. The resulting pluripotent cells, called induced pluripotent stem (iPS) cells, could be an alternative to embryonic stem cells, which are under continuous ethical debate. Hence, iPS cell-derived functional cells such as neurons may become the key for an effective treatment of currently incurable degenerative diseases. However, besides the requirement of efficacy testing of the therapy also its long-term safety needs to be carefully evaluated in settings mirroring the clinical situation in an optimal way. In this context, we chose the long-lived common marmoset monkey (Callithrix jacchus) as a non-human primate species to generate iPS cells. The marmoset monkey is frequently used in biomedical research and is gaining more and more preclinical relevance due to the increasing number of disease models. Here, we describe, to our knowledge, the first-time generation of marmoset monkey iPS cells from postnatal skin fibroblasts by non-viral means. We used the transposon-based, fully reversible piggyback system. We cloned the marmoset monkey reprogramming factors and established robust and reproducible reprogramming protocols with a six-factor-in-one-construct approach. We generated six individual iPS cell lines and characterized them in comparison with marmoset monkey embryonic stem cells. The generated iPS cells are morphologically indistinguishable from marmoset ES cells. The iPS cells are fully reprogrammed as demonstrated by differentiation assays, pluripotency marker expression and transcriptome analysis. They are stable for numerous passages (more than 80) and exhibit euploidy. In summary, we have established efficient non-viral reprogramming protocols for the derivation of stable marmoset monkey iPS cells, which can be used to develop and test cell replacement therapies in

  4. Thrombin generation and fibrin clot formation under hypothermic conditions: an in vitro evaluation of tissue factor initiated whole blood coagulation

    PubMed Central

    Whelihan, Matthew F.; Kiankhooy, Armin; Brummel-Ziedins, Kathleen

    2015-01-01

    Background Despite trauma-induced hypothermic coagulopathy being familiar in the clinical setting, empirical experimentation concerning this phenomenon is lacking. In this study we investigated the effects of hypothermia on thrombin generation, clot formation and global hemostatic functions in an in vitro environment using a whole blood model and thromboelastography (TEG) which can recapitulate hypothermia. Methods Blood was collected from healthy individuals through venipuncture and treated with corn trypsin inhibitor, to block the contact pathway. Coagulation was initiated with 5pM tissue factor at temperatures 37°C, 32°C, and 27°C. Reactions were quenched over time with soluble and insoluble components of each time point analyzed for thrombin generation, fibrinogen consumption, factor (f)XIII activation and fibrin deposition. Global coagulation potential was evaluated through TEG. Results Data showed that thrombin generation in samples at 37°C and 32°C had comparable rates while 27°C had a much lower rate (39.2 ± 1.1 and 43 ± 2.4 nM/min vs 28.6 ± 4.4 nM/min, respectively). Fibrinogen consumption and fXIII activation were highest at 37°C followed by 32°C and 27°C (13.8 ± 2.9 percent/min vs 7.8 ± 1.8 percent/min, respectively). Fibrin formation as seen through clot weights also followed this trend. TEG data showed clot formation was fastest in samples at 37°C and lowest at 27°C. Maximum clot strength was similar for each temperature. Also, percent lysis of clots was highest at 37°C followed by 32°C and then 27°C. Conclusions Induced hypothermic conditions directly affect the rate of thrombin generation and clot formation while global clot stability remains intact. PMID:24331944

  5. Factors affecting the pore space transformation during hydrocarbon generation in source rock (shales): laboratory experiment

    NASA Astrophysics Data System (ADS)

    Giliazetdinova, D. R.; Korost, D. V.

    2014-12-01

    Oil and gas generation is a set of processes which taking place in the interior, the processes can't be observable in nature. In the process of dumping the source rock, organic matter is transformed into a complex of high-molecular compounds - precursors of oil and gas (kerogen). Entering of a source column for specific thermobaric conditions, triggers the formation of low molecular weight hydrocarbon compounds. Generation of sufficient quantities of hydrocarbons leads to the primary fluid migration within the source rock. For the experiment were selected mainly siliceous-carbonate composition rocks from Domanic horizon South-Tatar arch. The main aim of experiment was heating the rocks in the pyrolyzer to temperatures which correspond katagenes stages. For monitoring changes in the morphology of the pore space X-ray microtomography method was used. As a result, when was made a study of the composition of mineral and organic content of the rocks, as well as textural and structural features, have been identified that the majority of the rock samples within the selected collection are identical. However, characteristics such as organic content and texture of rocks are different. Thus, the experiment was divided into two parts: 1) the study of the influence of organic matter content on the morphology of the rock in the process of thermal effects; 2) study the effect of texture on the primary migration processes for the same values of organic matter. Also, an additional experiment was conducted to study the dynamics of changes in the structure of the pore space. At each stage of the experiment morphology of altered rocks characterized by the formation of new pores and channels connecting the primary voids. However, it was noted that the samples with a relatively low content of the organic matter had less changes in pore space morphology, in contrast to rocks with a high organic content. At the second stage of the research also revealed that the conversion of the pore

  6. Potentiation of thrombin generation in hemophilia A plasma by coagulation factor VIII and characterization of antibody-specific inhibition.

    PubMed

    Doshi, Bhavya S; Gangadharan, Bagirath; Doering, Christopher B; Meeks, Shannon L

    2012-01-01

    Development of inhibitory antibodies to coagulation factor VIII (fVIII) is the primary obstacle to the treatment of hemophilia A in the developed world. This adverse reaction occurs in 20-30% of persons with severe hemophilia A treated with fVIII-replacement products and is characterized by the development of a humoral and neutralizing immune response to fVIII. Patients with inhibitory anti-fVIII antibodies are treated with bypassing agents including recombinant factor VIIa (rfVIIa). However, some patients display poor hemostatic response to bypass therapy and improved treatment options are needed. Recently, we demonstrated that fVIII inhibitors display widely variable kinetics of inhibition that correlate with their respective target epitopes. Thus, it was hypothesized that for antibodies that display slow rates of inhibition, supplementation of rfVIIa with fVIII would result in improved thrombin generation and be predictive of clinical responses to this novel treatment regimen. In order to test this hypothesis, 10 murine monoclonal antibodies (MAbs) with non-overlapping epitopes spanning fVIII, differential inhibition titers, and inhibition kinetics were studied using a thrombin generation assay. Of the 3 MAbs with high inhibitory titers, only the one with fast and complete (classically defined as "type I") kinetics displayed significant inhibition of thrombin generation with no improvement upon supplementation of rfVIIa with fVIII. The other two MAbs that displayed incomplete (classically defined as "type II") inhibition did not suppress the potentiation of thrombin generation by fVIII. All antibodies that did not completely inhibit fVIII activity demonstrated potentiation of thrombin generation by the addition of fVIII as compared to rfVIIa alone. In conclusion, fVIII alone or in combination with rfVIIa corrects the thrombin generation defect produced by the majority of anti-fVIII MAbs better than single agent rfVIIa. Therefore, combined fVIII/rfVIIa therapy

  7. Probabilistic Inference on Multiple Normalized Signal Profiles from Next Generation Sequencing: Transcription Factor Binding Sites.

    PubMed

    Wong, Ka-Chun; Peng, Chengbin; Li, Yue

    2015-01-01

    With the prevalence of chromatin immunoprecipitation (ChIP) with sequencing (ChIP-Seq) technology, massive ChIP-Seq data has been accumulated. The ChIP-Seq technology measures the genome-wide occupancy of DNA-binding proteins in vivo. It is well-known that different DNA-binding protein occupancies may result in a gene being regulated in different conditions (e.g. different cell types). To fully understand a gene's function, it is essential to develop probabilistic models on multiple ChIP-Seq profiles for deciphering the gene transcription causalities. In this work, we propose and describe two probabilistic models. Assuming the conditional independence of different DNA-binding proteins' occupancies, the first method (SignalRanker) is developed as an intuitive method for ChIP-Seq genome-wide signal profile inference. Unfortunately, such an assumption may not always hold in some gene regulation cases. Thus, we propose and describe another method (FullSignalRanker) which does not make the conditional independence assumption. The proposed methods are compared with other existing methods on ENCODE ChIP-Seq datasets, demonstrating its regression and classification ability. The results suggest that FullSignalRanker is the best-performing method for recovering the signal ranks on the promoter and enhancer regions. In addition, FullSignalRanker is also the best-performing method for peak sequence classification. We envision that SignalRanker and FullSignalRanker will become important in the era of next generation sequencing. FullSignalRanker program is available on the following website: http://www.cs.toronto.edu/~wkc/FullSignalRanker/.

  8. Probabilistic Inference on Multiple Normalized Signal Profiles from Next Generation Sequencing: Transcription Factor Binding Sites.

    PubMed

    Wong, Ka-Chun; Peng, Chengbin; Li, Yue

    2015-01-01

    With the prevalence of chromatin immunoprecipitation (ChIP) with sequencing (ChIP-Seq) technology, massive ChIP-Seq data has been accumulated. The ChIP-Seq technology measures the genome-wide occupancy of DNA-binding proteins in vivo. It is well-known that different DNA-binding protein occupancies may result in a gene being regulated in different conditions (e.g. different cell types). To fully understand a gene's function, it is essential to develop probabilistic models on multiple ChIP-Seq profiles for deciphering the gene transcription causalities. In this work, we propose and describe two probabilistic models. Assuming the conditional independence of different DNA-binding proteins' occupancies, the first method (SignalRanker) is developed as an intuitive method for ChIP-Seq genome-wide signal profile inference. Unfortunately, such an assumption may not always hold in some gene regulation cases. Thus, we propose and describe another method (FullSignalRanker) which does not make the conditional independence assumption. The proposed methods are compared with other existing methods on ENCODE ChIP-Seq datasets, demonstrating its regression and classification ability. The results suggest that FullSignalRanker is the best-performing method for recovering the signal ranks on the promoter and enhancer regions. In addition, FullSignalRanker is also the best-performing method for peak sequence classification. We envision that SignalRanker and FullSignalRanker will become important in the era of next generation sequencing. FullSignalRanker program is available on the following website: http://www.cs.toronto.edu/~wkc/FullSignalRanker/. PMID:26671811

  9. Generation of sensory hair cells by genetic programming with a combination of transcription factors.

    PubMed

    Costa, Aida; Sanchez-Guardado, Luis; Juniat, Stephanie; Gale, Jonathan E; Daudet, Nicolas; Henrique, Domingos

    2015-06-01

    Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. Elucidation of the transcriptional networks regulating HC fate determination and differentiation is crucial not only to understand inner ear development but also to improve cell replacement therapies for hearing disorders. Here, we show that combined expression of the transcription factors Gfi1, Pou4f3 and Atoh1 can induce direct programming towards HC fate, both during in vitro mouse embryonic stem cell differentiation and following ectopic expression in chick embryonic otic epithelium. Induced HCs (iHCs) express numerous HC-specific markers and exhibit polarized membrane protrusions reminiscent of stereociliary bundles. Transcriptome profiling confirms the progressive establishment of a HC-specific gene signature during in vitro iHC programming. Overall, this work provides a novel approach to achieve robust and highly efficient HC production in vitro, which could be used as a model to study HC development and to drive inner ear HC regeneration.

  10. Generating correlation matrices with model error for simulation studies in factor analysis: a combination of the Tucker-Koopman-Linn model and Wijsman's algorithm.

    PubMed

    Hong, S

    1999-11-01

    Most simulation studies in factor analysis follow a process of constructing population correlation matrices from the common-factor model and generating sample correlation matrices from the population matrices. In the common-factor model, the population correlation matrix is perfectly fit by the model's containing common and unique factors. However, since no mathematical model accounts exactly for the real-world phenomena that it is intended to represent, the Tucker-Koopman-Linn model (1969) is more realistic for generating correlation matrices than the conventional common-factor model because the former incorporates model error. In this paper, a procedure for generating population and sample correlation matrices with model error by combining the Tucker-Koopman-Linn model and Wijsman's algorithm (1959) is presented. The SAS/IML program for generating correlation matrices is described, and an example is also provided.

  11. Factors influencing the study of peroxidase-generated iodine species and implications for thyroglobulin synthesis.

    PubMed

    Kessler, Jack; Obinger, Christian; Eales, Geoff

    2008-07-01

    A key issue in the mechanism of thyroglobulin (Tg) iodination by thyroperoxidase (TPO) is whether a TPO-bound iodine intermediate directly iodinates Tg-incorporated tyrosines (specific iodination) or whether reactive iodine species released from TPO effectuate Tg iodination (nonspecific iodination). We addressed these alternatives by (a) determining the aqueous equilibria of the iodine species potentially involved in the kinetic studies of TPO-mediated iodination, and (b) reviewing the structure of the substrate channel in mammalian peroxidases. Redox-potentiometric analysis of aqueous iodine combined with integrated mathematical modelling demonstrates that I2 reacts with water to form several iodine species including hypoiodious acid (HOI). The HOI/I2 ratio depends on time, iodide concentration, buffering agents, and pH varying dramatically from pH 4 to 7.4. These factors may confound the use of Michaelis-Menten kinetics to determine the mechanism of TPO-catalyzed iodination since both I2 and HOI iodinate tyrosine but with different specificities and reaction rates. Consequently there is as yet no conclusive kinetic evidence that iodination occurs via formation of a TPO-bound iodinated intermediate. Furthermore, knowledge of TPO structure, gained from X-ray crystallographic studies indicates that access of Tg-bound tyrosyl groups to the active site of TPO is not possible. Thus the emerging conclusion is that the mechanism of Tg iodination is nonspecific. This is consistent with the occurrence of thyroid hormone formation in prevertebrate ascidians which exhibit TPO-like activity but lack the Tg gene.

  12. Analysis of Pre-Analytic Factors Affecting the Success of Clinical Next-Generation Sequencing of Solid Organ Malignancies

    PubMed Central

    Chen, Hui; Luthra, Rajyalakshmi; Goswami, Rashmi S.; Singh, Rajesh R.; Roy-Chowdhuri, Sinchita

    2015-01-01

    Application of next-generation sequencing (NGS) technology to routine clinical practice has enabled characterization of personalized cancer genomes to identify patients likely to have a response to targeted therapy. The proper selection of tumor sample for downstream NGS based mutational analysis is critical to generate accurate results and to guide therapeutic intervention. However, multiple pre-analytic factors come into play in determining the success of NGS testing. In this review, we discuss pre-analytic requirements for AmpliSeq PCR-based sequencing using Ion Torrent Personal Genome Machine (PGM) (Life Technologies), a NGS sequencing platform that is often used by clinical laboratories for sequencing solid tumors because of its low input DNA requirement from formalin fixed and paraffin embedded tissue. The success of NGS mutational analysis is affected not only by the input DNA quantity but also by several other factors, including the specimen type, the DNA quality, and the tumor cellularity. Here, we review tissue requirements for solid tumor NGS based mutational analysis, including procedure types, tissue types, tumor volume and fraction, decalcification, and treatment effects. PMID:26343728

  13. Adaptation to hydrogen peroxide in Saccharomyces cerevisiae: the role of NADPH-generating systems and the SKN7 transcription factor.

    PubMed

    Ng, Chong-Han; Tan, Shi-Xiong; Perrone, Gabriel G; Thorpe, Geoffrey W; Higgins, Vincent J; Dawes, Ian W

    2008-03-15

    A total of 286 H2O2-sensitive Saccharomyces cerevisiae deletion mutants were screened to identify genes involved in cellular adaptation to H2O2 stress. YAP1, SKN7, GAL11, RPE1, TKL1, IDP1, SLA1, and PET8 were important for adaptation to H2O2. The mutants were divisible into two groups based on their responses to a brief acute dose of H2O2 and to chronic exposure to H2O2. Transcription factors Yap1p, Skn7p, and Gal11p were important for both acute and chronic responses to H2O2. Yap1p and Skn7p were acting in concert for adaptation, which indicates that upregulation of antioxidant functions rather than generation of NADPH or glutathione is important for adaptation. Deletion of GPX3 and YBP1 involved in sensing H2O2 and activating Yap1p affected adaptation but to a lesser extent than YAP1 deletion. NADPH generation was also required for adaptation. RPE1, TKL1, or IDP1 deletants affected in NADPH production were chronically sensitive to H2O2 but resistant to an acute dose, and other mutants affected in NADPH generation tested were similarly affected in adaptation. These mutants overproduced reduced glutathione (GSH) but maintained normal cellular redox homeostasis. This overproduction of GSH was not regulated at transcription of the gene encoding gamma-glutamylcysteine synthetase. PMID:18206664

  14. Generation of Potent Anti-Vascular Endothelial Growth Factor Neutralizing Antibodies from Mouse Phage Display Library for Cancer Therapy

    PubMed Central

    Lai, Yan-Da; Wu, Yen-Yu; Tsai, Yi-Jiue; Tsai, Yi-San; Lin, Yu-Ying; Lai, Szu-Liang; Huang, Chao-Yang; Lok, Ying-Yung; Hu, Chih-Yung; Lai, Jiann-Shiun

    2016-01-01

    Vascular endothelial growth factor (VEGF) is an important stimulator for angiogenesis in solid tumors. Blocking VEGF activity is an effective therapeutic strategy to inhibit tumor growth and metastasis. Avastin, a humanized monoclonal antibody recognizes VEGF, has been approved by the US Food and Drug Administration. To generate potential VEGF-recognizing antibodies with better tumor regression ability than that of Avastin, we have designed a systematic antibody selection plan. From mice immunized with recombinant human VEGF, we generated three phage display libraries, scFv-M13KO7, Fab-M13KO7, and scFv-Hyperphage, in single-chain Fv (scFv) or Fab format, displayed using either M13KO7 helper phage or Hyperphage. Solid-phase and solution-phase selection strategies were then applied to each library, generating six panning combinations. A total of sixty-four antibodies recognizing VEGF were obtained. Based on the results of epitope mapping, binding affinity, and biological functions in tumor inhibition, eight antibodies were chosen to examine their abilities in tumor regression in a mouse xenograft model using human COLO 205 cancer cells. Three of them showed improvement in the inhibition of tumor growth (328%–347% tumor growth ratio (% of Day 0 tumor volume) on Day 21 vs. 435% with Avastin). This finding suggests a potential use of these three antibodies for VEGF-targeted therapy. PMID:26861297

  15. Mendelian Factors Underlying Quantitative Traits in Tomato: Comparison across Species, Generations, and Environments

    PubMed Central

    Paterson, A. H.; Damon, S.; Hewitt, J. D.; Zamir, D.; Rabinowitch, H. D.; Lincoln, S. E.; Lander, E. S.; Tanksley, S. D.

    1991-01-01

    of the F(2) parent at QTLs than from the phenotype of the F(2) individual. For a trait with intermediate heritability (fruit pH), QTL genotype and observed phenotype were about equally effective at predicting progeny phenotype. For a trait with high heritability (mass per fruit), knowing the QTL genotype of an individual added little if any predictive value, to simply knowing the phenotype. The QTLs mapped in the L. esculentum X L. cheesmanii F(2) appear to be at similar locations to many of those mapped in a previous cross with a different wild tomato (L. chmielewskii). One possible explanation of this similarity is that genetic factors at some of the same loci may affect the traits in the two distantly-related wild species. Potentially major implications of such similarity across broad genetic distances are discussed, in regard to plant and animal breeding, germplasm introgression, and cloning of QTLs. PMID:1673106

  16. Changes in hormone and lipid levels in male patients with focal seizures when switched from carbamazepine to lacosamide as adjunctive treatment to levetiracetam: A small phase IIIb, prospective, multicenter, open-label trial.

    PubMed

    Elger, Christian E; Rademacher, Michael; Brandt, Christian; Elmoufti, Sami; Dedeken, Peter; Eckhardt, Klaus; Tennigkeit, Frank; De Backer, Marc

    2016-09-01

    Treatment with enzyme-inducing antiepileptic drugs (AEDs) such as carbamazepine (CBZ) can lead to changes in reproductive, endocrine, and lipid parameters, resulting in clinical symptoms for some patients. Previous studies indicate that these changes can be reversed by switching to a nonenzyme-inducing AED. Lacosamide is a newer-generation AED, not known to induce or strongly inhibit cytochrome P450 (CYP450) enzymes. In this phase IIIb, prospective, multicenter, open-label, single-arm trial (NCT01375374), the serum concentrations of CYP-related reproductive hormones, thyroid hormones, and lipids were assessed in otherwise healthy male patients with focal seizures (N=11), before and after a switch from CBZ (600-1200mg/day at baseline) to lacosamide (target dose: 400mg/day by the end of titration) as adjunctive treatment to the nonenzyme-inducing AED levetiracetam (LEV, stable dosage of >1000mg/day throughout). Cross titration took place over 4weeks, followed by an 8-week maintenance period. Serum measurements were conducted at baseline and at the end of maintenance. The median serum sex-hormone-binding globulin (SHBG) concentration was towards the higher end of the normal range at baseline and decreased following the switch (61.7 to 47.5nmol/L, N=10, p=0.027 by Wilcoxon signed-rank test). Free androgen index (100×testosterone/SHBG) and free thyroxine serum concentration increased (25.4 to 36.4 and 13.0 to 14.9pmol/L, respectively, both N=10 and p=0.002). At baseline, the median progesterone serum concentration was below the normal range (0.7nmol/L), whereas median cholesterol and low-density lipoprotein concentrations were above the normal range (5.5 and 3.6mmol/L, respectively). By the end of maintenance, all measured parameters were within the normal range. The safety and tolerability profile of lacosamide was consistent with that observed in previous studies. Furthermore, antiseizure efficacy appeared to be maintained, suggesting that deinduction of CYP enzymes

  17. Factors expressed by murine embryonic pancreatic mesenchyme enhance generation of insulin-producing cells from hESCs.

    PubMed

    Guo, Tingxia; Landsman, Limor; Li, Na; Hebrok, Matthias

    2013-05-01

    Islet transplantation has proven to be a successful strategy to restore normoglycemia in patients with type 1 diabetes (T1D). However, the dearth of cadaveric islets available for transplantation hampers the widespread application of this treatment option. Although human embryonic stem cells and induced pluripotent stem cells are capable of generating insulin-producing cells in vitro when provided with the appropriate inductive cues, the insulin-expressing cells that develop behave more like immature β-cells with minimal sensitivity to glucose stimulation. Here, we identify a set of signaling factors expressed in mouse embryonic mesenchyme during the time when foregut and pancreatic progenitors are specified and test their activities during in vitro differentiation of human embryonic stem cells. Several of the identified factors work in concert to expand the pancreatic progenitor pool. Interestingly, transforming growth factor (TGF)-β ligands, most potent in inducing pancreatic progenitors, display strong inhibitory effects on subsequent endocrine cell differentiation. Treatment with TGF-β ligands, followed by the addition of a TGF-β receptor antagonist, dramatically increased the number of insulin-producing cells in vitro, demonstrating the need for dynamic temporal regulation of TGF-β signaling during in vitro differentiation. These studies illustrate the need to precisely mimic the in vivo conditions to fully recapitulate pancreatic lineage specification in vitro. PMID:23305648

  18. Experience with a third generation recombinant factor VIII concentrate (Advate) for immune tolerance induction in patients with haemophilia A.

    PubMed

    Valentino, L A; Recht, M; Dipaola, J; Shapiro, A D; Pipe, S W; Ewing, N; Urgo, J; Bullock, T; Simmons, M; Deguzman, C

    2009-05-01

    The development of an inhibitor represents one of the most challenging complications in patients with haemophilia A. Optimal management is immune tolerance induction (ITI), typically through the administration of high doses of factor VIII (FVIII) concentrate. Among 12 patients who underwent ITI using Advate, a third-generation recombinant FVIII product that is free of animal and human protein additives, tolerance was achieved in nine (75%), including seven of 10 patients (70%) with high-titre inhibitors. ITI is ongoing in two patients and not yet successful; immune tolerance failed in the third patient. The median time to success was 4.0 months for group as a whole and for patients with high-titre inhibitors. Treatment was well tolerated, and no adverse events were observed. Advate was found to be equivalent to other FVIII products with regard to both ITI success rates and the incidence of adverse effects when used in these immune tolerance regimens. PMID:19298383

  19. Impact of experimental haemodilution on platelet function, thrombin generation and clot firmness: effects of different coagulation factor concentrates

    PubMed Central

    Caballo, Carolina; Escolar, Gines; Diaz-Ricart, Maribel; Lopez-Vílchez, Irene; Lozano, Miguel; Cid, Joan; Pino, Marcos; Beltrán, Joan; Basora, Misericordia; Pereira, Arturo; Galan, Ana M.

    2013-01-01

    Background Haemodilution during resuscitation after massive haemorrhage may worsen the coagulopathy and perpetuate bleeding. Materials and methods Blood samples from healthy donors were diluted (30 and-60%) using crystalloids (saline, Ringer’s lactate, PlasmalyteTM) or colloids (6% hydroxyethylstarch [HES130/0.4], 5% human albumin, and gelatin). The effects of haemodilution on platelet adhesion (Impact R), thrombin generation (TG), and thromboelastometry (TEM) parameters were analysed as were the effects of fibrinogen, prothrombin complex concentrates (PCC), activated recombinant factor VII (FVIIa), and cryoprecipates on haemodilution. Results Platelet interactions was already significantly reduced at 30% haemodilution. Platelet reactivity was not improved by addition of any of the concentrates tested. A decrease in TG and marked alterations of TEM parameters were noted at 60% haemodilution. HES130/0.4 was the expander with the most deleterious action. TG was significantly enhanced by PCC whereas rFVIIa only caused a mild acceleration of TG initiation. Fibrinogen restored the alterations of TEM parameters caused by haemodilution including those caused by HES 130/0.4. Cryoprecipitates significantly improved the alterations caused by haemodilution on TG and TEM parameters; the effects on TG disappeared after ultracentrifugation of the cryoprecipitates. Discussion The haemostatic alterations caused by haemodilution are multifactorial and affect both blood cells and coagulation. In our in vitro approach, HES 130/0.4 had the most deleterious effect on haemostasis parameters. Coagulation factor concentrates did not improve platelet interactions in the Impact R, but did have favourable effects on coagulation parameters measured by TG and TEM. Fibrinogen notably improved TEM parameters without increasing thrombin generation, suggesting that this concentrate may help to preserve blood clotting abilities during haemodilution without enhancing the prothrombotic risk. PMID

  20. Enrollment Factors that Predict Persistence of At-Risk (Low Income and First Generation) Students' Journey towards Completion of a Baccalaureate Degree at Idaho State University

    ERIC Educational Resources Information Center

    Yizar, James H., Jr.

    2010-01-01

    The purpose of this study was to explore, track, and predict longitudinal differences (over the course of six years beginning fall semester 2001) between and among ISU low income, first generation, or the combination of low income and first generation freshman students; regarding persistence rate, and associated persistence factors, such as ACT…

  1. Neutrophil Elastase-Generated Fragment of Vascular Endothelial Growth Factor-A Stimulates Macrophage and Endothelial Progenitor Cell Migration

    PubMed Central

    Kurtagic, Elma; Rich, Celeste B.; Buczek-Thomas, Jo Ann; Nugent, Matthew A.

    2015-01-01

    Elastase released from neutrophils as part of the innate immune system has been implicated in chronic diseases such as emphysema and cardiovascular disease. We have previously shown that neutrophil elastase targets vascular endothelial growth factor-A (VEGF) for partial degradation to generate a fragment of VEGF (VEGFf) that has distinct activities. Namely, VEGFf binds to VEGF receptor 1 but not to VEGF receptor 2 and shows altered signaling compared to intact VEGF. In the present study we investigated the chemotactic function of VEGF and VEGFf released from cells by neutrophil elastase. We found that endothelial cells migrated in response to intact VEGF but not VEGFf whereas RAW 264.7 macrophages/monocytes and embryonic endothelial progenitor cells were stimulated to migrate by either VEGF or VEGFf. To investigate the role of elastase-mediated release of VEGF from cells/extracellular matrices, a co-culture system was established. High or low VEGF producing cells were co-cultured with macrophages, endothelial or endothelial progenitor cells and treated with neutrophil elastase. Elastase treatment stimulated macrophage and endothelial progenitor cell migration with the response being greater with the high VEGF expressing cells. However, elastase treatment led to decreased endothelial cell migration due to VEGF cleavage to VEGF fragment. These findings suggest that the tissue response to NE-mediated injury might involve the generation of diffusible VEGF fragments that stimulate inflammatory cell recruitment. PMID:26672607

  2. Generational diversity.

    PubMed

    Kramer, Linda W

    2010-01-01

    Generational diversity has proven challenges for nurse leaders, and generational values may influence ideas about work and career planning. This article discusses generational gaps, influencing factors and support, and the various generational groups present in today's workplace as well as the consequences of need addressing these issues. The article ends with a discussion of possible solutions.

  3. Generational diversity.

    PubMed

    Kramer, Linda W

    2010-01-01

    Generational diversity has proven challenges for nurse leaders, and generational values may influence ideas about work and career planning. This article discusses generational gaps, influencing factors and support, and the various generational groups present in today's workplace as well as the consequences of need addressing these issues. The article ends with a discussion of possible solutions. PMID:20395729

  4. Trophoblastic cell lines generated from tumour necrosis factor receptor-deficient mice reveal specific functions for the two tumour necrosis factor receptors.

    PubMed

    Rasmussen, C A; Pace, J L; Banerjee, S; Phillips, T A; Hunt, J S

    1999-01-01

    In mice and humans, expression of the tumour necrosis factor receptor-1 (TNF-R1) gene in placental trophoblast cells is constitutive whereas expression of the TNF-R2 gene is developmentally programmed. In order to study the individual functions of TNF-R1 and -R2 in this lineage, cell lines were generated from placental explants of homozygous matings of gestation day 10 outbred mice (Swiss-Webster), TNF-R1-deficient (TNF-R1-/-) and TNF-R2-/- transgenic mice as well as the background strain for the TNF-R2-/- mice (WT, C57BL/6x129). All of the cells exhibited trophoblast markers; they contained cytokeratin intermediate filaments, expressed alkaline phosphatase activity and displayed transferrin receptors, but were negative for vimentin filaments and the macrophage marker, F4/80. Analysis of DNA by polymerase chain reaction demonstrated the expected TNF-R genotype in each line. In experiments testing the effects of recombinant mouse TNF-alpha (rmTNF-alpha) on viability and proliferation of the cell lines, rmTNF-alpha modestly but dose-dependently inhibited the growth of WT and TNF-R2-/- cells while having no effect on TNF-R1-/- cells. Actinomycin D-treated WT and, to a lesser extent, TNF-R2-/- cells, were more sensitive to growth inhibition than untreated cells whereas TNF-R1-/- cell responses remained unchanged. These data indicated that rmTNF-alpha inhibits growth of trophoblastic cells through TNF-R1 and that newly synthesized protein(s) provide partial protection against toxicity. In contrast to the receptor species-specific effects on cell growth exerted by rmTNF-alpha, both TNF-R mediated inhibition of alkaline phosphatase activity. Collectively, the observations support the postulate that receptor expression is the key factor which determines the nature and extent of TNF-alpha effects on trophoblast cell growth and function.

  5. Pathways by which the interplay of organismic and environmental factors lead to phenotypic variation within and across generations.

    PubMed

    Harper, Lawrence V

    2013-01-01

    The range of responses made to environmental exigencies by animals, including humans, may be impacted by the experiences of their progenitors. In mammals, pathways have been documented ranging from transactions between a mother and her developing fetus in the womb through continuity of parenting practices and cultural inheritance. In addition, phenotypic plasticity may be constrained by factors transmitted by the gametes that are involved in the regulation of gene expression rather than modifications to the genome itself. Possible mediators for this kind of inheritance are examined, and the conditions that might have led to the evolution of such transmission are considered. Anticipatory adjustments to possible environmental exigencies are likely to occur when such conditions recur regularly, but intermittently across generations and endure for substantial periods of time, and when adjusting to them after the fact is likely to be biologically costly, even life-threatening. It appears that physical growth and responses to nutrient availability are domains in which anticipatory, epigenetically inherited adjustments occur. In addition, given the fact that humans have oppressed one another repeatedly and for relatively long periods of time, such behavioral tendencies as boldness or innovativeness may be behavioral traits subject to such effects. The implications of these factors for research and policy are discussed.

  6. Phenotypic features of first-generation transgenic goats for human granulocyte-colony stimulation factor production in milk.

    PubMed

    Batista, Ribrio I T P; Melo, Carlos H S; Souza-Fabjan, Joanna M G; Teixeira, Dárcio I A; Melo, Luciana M; Freitas, Vicente J F

    2014-11-01

    Human granulocyte-colony stimulating factor (hG-CSF) is a hematopoietic growth factor used in neutropenic patients. It is produced in transgenic bacteria or cultured mammalian cells. As an alternative, we now show that hG-CSF can be expressed in the mammary gland of first-generation (F1) transgenic goats during induced lactation. Despite lower milk production, transgenic females presented a similar milk composition (fat, protein and lactose) when compared to non-transgenic (p > 0.05) ones. The mean concentration (±SD) of recombinant hG-CSF in milk during lactation was 360 ± 178 µg ml(-1). All clinical parameters, as well as kidney and liver function, indicated that F1 transgenic goats were healthy. Additionally, no ectopic hG-CSF expression was detected in studied tissues of F1 transgenic males. Thus, F1 hG-CSF-transgenic goats can express the recombinant protein in milk at quantities compatible with their use as bioreactors in a commercial-scale protein-production program.

  7. Changes in the Factors Influencing Public Acceptance of Nuclear Power Generation in Japan Since the 2011 Fukushima Daiichi Nuclear Disaster.

    PubMed

    Tsujikawa, Norifumi; Tsuchida, Shoji; Shiotani, Takamasa

    2016-01-01

    Public support for nuclear power generation has decreased in Japan since the Fukushima Daiichi nuclear accident in March 2011. This study examines how the factors influencing public acceptance of nuclear power changed after this event. The influence factors examined are perceived benefit, perceived risk, trust in the managing bodies, and pro-environmental orientation (i.e., new ecological paradigm). This study is based on cross-sectional data collected from two online nationwide surveys: one conducted in November 2009, before the nuclear accident, and the other in October 2011, after the accident. This study's target respondents were residents of Aomori, Miyagi, and Fukushima prefectures in the Tohoku region of Japan, as these areas were the epicenters of the Great East Japan Earthquake and the locations of nuclear power stations. After the accident, trust in the managing bodies was found to have a stronger influence on perceived risk, and pro-environmental orientation was found to have a stronger influence on trust in the managing bodies; however, perceived benefit had a weaker positive influence on public acceptance. We also discuss the theoretical and practical implications of these findings. PMID:26224041

  8. Changes in the Factors Influencing Public Acceptance of Nuclear Power Generation in Japan Since the 2011 Fukushima Daiichi Nuclear Disaster.

    PubMed

    Tsujikawa, Norifumi; Tsuchida, Shoji; Shiotani, Takamasa

    2016-01-01

    Public support for nuclear power generation has decreased in Japan since the Fukushima Daiichi nuclear accident in March 2011. This study examines how the factors influencing public acceptance of nuclear power changed after this event. The influence factors examined are perceived benefit, perceived risk, trust in the managing bodies, and pro-environmental orientation (i.e., new ecological paradigm). This study is based on cross-sectional data collected from two online nationwide surveys: one conducted in November 2009, before the nuclear accident, and the other in October 2011, after the accident. This study's target respondents were residents of Aomori, Miyagi, and Fukushima prefectures in the Tohoku region of Japan, as these areas were the epicenters of the Great East Japan Earthquake and the locations of nuclear power stations. After the accident, trust in the managing bodies was found to have a stronger influence on perceived risk, and pro-environmental orientation was found to have a stronger influence on trust in the managing bodies; however, perceived benefit had a weaker positive influence on public acceptance. We also discuss the theoretical and practical implications of these findings.

  9. Generation and characterization of leukemia inhibitory factor-dependent equine induced pluripotent stem cells from adult dermal fibroblasts.

    PubMed

    Whitworth, Deanne J; Ovchinnikov, Dmitry A; Sun, Jane; Fortuna, Patrick R J; Wolvetang, Ernst J

    2014-07-01

    In this study we have reprogrammed dermal fibroblasts from an adult female horse into equine induced pluripotent stem cells (equiPSCs). These equiPSCs are dependent only on leukemia inhibitory factor (LIF), placing them in striking contrast to previously derived equiPSCs that have been shown to be co-dependent on both LIF and basic fibroblast growth factor (bFGF). These equiPSCs have a normal karyotype and have been maintained beyond 60 passages. They possess alkaline phosphatase activity and express eqNANOG, eqOCT4, and eqTERT mRNA. Immunocytochemistry confirmed that they produce NANOG, REX1, SSEA4, TRA1-60, and TRA1-81. While our equiPSCs are LIF dependent, bFGF co-stimulates their proliferation via the PI3K/AKT pathway. EquiPSCs lack expression of eqXIST and immunostaining for H3K27me3, suggesting that during reprogramming the inactive X chromosome has likely been reactivated to generate cells that have two active X chromosomes. EquiPSCs form embryoid bodies and in vitro teratomas that contain derivatives of all three germ layers. These LIF-dependent equiPSCs likely reflect a more naive state of pluripotency than equiPSCs that are co-dependent on both LIF and bFGF and so provide a novel resource for understanding pluripotency in the horse.

  10. ISO standardization of scaling factor method for low and intermediate level radioactive wastes generated at nuclear power plants

    SciTech Connect

    Kashiwagi, Makoto; Masui, Hideki; Denda, Yasutaka; James, David; Lantes, Bertrand; Mueller, Wolfgang; Garamszeghy, Mike; Leganes, Jose Luis; Maxeiner, Harald; Van Velzen, Leo

    2007-07-01

    Low- and intermediate-level radioactive wastes (L-ILW ) generated at nuclear power plants are disposed of in various countries. In the disposal of such wastes, it is required that the radioactivity concentrations of waste packages should be declared with respect to difficult-to-measure nuclides (DTM nuclides), such as C-14, Ni-63 and a-emitting nuclides, which are often limited to maximum values in disposal licenses, safety cases and/or regulations for maximum radioactive concentrations. To fulfill this requirement, the Scaling Factor method (SF method) has been applied in various countries as a principal method for determining the concentrations of DTM nuclides. In the SF method, the concentrations of DTM nuclides are determined by multiplying the concentrations of certain key nuclides by SF values (the determined ratios of radioactive concentration between DTM nuclides and those key nuclides). The SF values used as conversion factors are determined from the correlation between DTM nuclides and key nuclides such as Co-60. The concentrations of key nuclides are determined by {gamma} ray measurements which can be made comparatively easily from outside the waste package. The SF values are calculated based on the data obtained from the radiochemical analysis of waste samples. The use of SFs, which are empirically based on analytical data, has become established as a widely recognized 'de facto standard'. A number of countries have independently collected nuclide data by analysis over many years and each has developed its own SF method, but all the SF methods that have been adopted are similar. The project team for standardization had been organized for establishing this SF method as a 'de jure standard' in the international standardization system of the International Organization for Standardization (ISO). The project team for standardization has advanced the standardization through technical studies, based upon each country's study results and analysis data. The

  11. A neuron-benign microfluidic gradient generator for studying the response of mammalian neurons towards axon guidance factors.

    PubMed

    Bhattacharjee, Nirveek; Li, Nianzhen; Keenan, Thomas M; Folch, Albert

    2010-11-01

    Investigation of biochemical cues in isolation or in combinations in cell culture systems is crucial for unraveling the mechanisms that govern neural development and repair. The most widely used experimental paradigms that elicit axon guidance in vitro utilize as the source of the gradient a pulsatile pipette, transfected cells, or a loaded gel, producing time-varying gradients of poor reproducibility which are not well suited for studying slow-growing mammalian cells. Although microfluidic device design have allowed for generating stable, complex gradients of diffusible molecules, the flow-induced shear forces in a microchannel has made it impossible to maintain viable mammalian neuronal cultures for sufficiently long times. In this paper, we describe axonal responses of mouse cortical neurons in a "neuron-benign" gradient-generator device based on an open chamber that can establish highly stable gradients of diffusible molecules for at least 6 h with negligible shear stress, and also allows the neurons to thrive for at least 2 weeks. Except for the period when the gradient is on, the cells in the gradient are under the same conditions as the cells on the control surfaces, which ensure a consistent set of micro-environmental variables. The gradient stability and uniformity over the cell culture surface achieved by the device, together with our software platform for acquiring, post-processing and quantitatively analyzing the large number of images allowed us to extract valuable information even from small datasets. We report a directed response of primary mammalian neurons (from E14 embryonic mice cortex) to a diffusible gradient of netrin in vitro. We infer from our studies that a large majority (∼73%) of the neurons that extend axons during the gradient application grow towards the netrin source, and our data analysis also indicates that netrin acts as a growth factor for this same population of neurons.

  12. Generation of mice carrying a knockout-first and conditional-ready allele of transforming growth factor beta2 gene.

    PubMed

    Ishtiaq Ahmed, A S; Bose, Gracelyn C; Huang, Li; Azhar, Mohamad

    2014-09-01

    Transforming growth factor beta2 (TGFβ2) is a multifunctional protein which is expressed in several embryonic and adult organs. TGFB2 mutations can cause Loeys Dietz syndrome, and its dysregulation is involved in cardiovascular, skeletal, ocular, and neuromuscular diseases, osteoarthritis, tissue fibrosis, and various forms of cancer. TGFβ2 is involved in cell growth, apoptosis, cell migration, cell differentiation, cell-matrix remodeling, epithelial-mesenchymal transition, and wound healing in a highly context-dependent and tissue-specific manner. Tgfb2(-/-) mice die perinatally from congenital heart disease, precluding functional studies in adults. Here, we have generated mice harboring Tgfb2(βgeo) (knockout-first lacZ-tagged insertion) gene-trap allele and Tgfb2(flox) conditional allele. Tgfb2(βgeo/βgeo) or Tgfb2(βgeo/-) mice died at perinatal stage from the same congenital heart defects as Tgfb2(-/-) mice. β-galactosidase staining successfully detected Tgfb2 expression in the heterozygous Tgfb2(βgeo) fetal tissue sections. Tgfb2(flox) mice were produced by crossing the Tgfb2(+/βgeo) mice with the FLPeR mice. Tgfb2(flox/-) mice were viable. Tgfb2 conditional knockout (Tgfb2(cko/-) ) fetuses were generated by crossing of Tgfb2(flox/-) mice with Tgfb2(+/-) ; EIIaCre mice. Systemic Tgfb2(cko/-) embryos developed cardiac defects which resembled the Tgfb2(βgeo/βgeo) , Tgfb2(βgeo/-) , and Tgfb2(-/-) fetuses. In conclusion, Tgfb2(βgeo) and Tgfb2(flox) mice are novel mouse strains which will be useful for investigating the tissue specific expression and function of TGFβ2 in embryonic development, adult organs, and disease pathogenesis and cancer. genesis

  13. Generation rates and emission factors of particulate matter and particle-bound polycyclic aromatic hydrocarbons of incense sticks.

    PubMed

    Lung, Shih-Chun Candice; Hu, Shu-Chuan

    2003-02-01

    The generation rates and emission factors of particulate matter and associated polycyclic aromatic hydrocarbons (PAHs) from incense burning were assessed in a laboratory setting. The differences among different segments of the same stick, among different sticks of the same kind of incense, and between two kinds of manually made Chih-Chen incense sticks (A and B) were evaluated. Joss sticks were burned inside a 44 cm long elutriator; personal environmental monitors fitted into the top of the elutriator were used to take PM2.5 and PM10 samples of incense smoke. Samples were analyzed for PAHs by gas chromatography-flame ionization Detector. It was found that particle and associated PAHs were generated approximately at 561 microg/min (geometric standard deviation (GSD) = 1.1) and 0.56 microg/min (GSD = 1.1) from Incense A, and at 661 microg/min (GSD = 1.7) and 0.46 microg/min (GSD = 1.3) from Incense B, respectively. One gram of Incense A emitted about 19.8 mg (GSD = 1.1) particulate matter and 17.1 microg (GSD = 1.2) particulate-phase PAHs, while one gram of Incense B produced around 43.6 mg (GSD = 1.1) of particles and 25.2 microg (GSD = 1.2) of particle-bound PAHs. There were significant differences in emissions between Incenses A and B, although they belong to the same class of incense. A 10-20% variability in emissions was observed in the main part of the manually produced stick, and a larger variation was found at both tips of the combustible part.

  14. Family Aggregation and Risk Factors in Phobic Disorders over Three-Generations in a Nation-Wide Study

    PubMed Central

    Steinhausen, Hans-Christoph; Jakobsen, Helle; Meyer, Andrea; Jørgensen, Povl Munk; Lieb, Roselind

    2016-01-01

    Objective This nation-wide register-based study investigated how often phobic disorders (PHO) and co-morbid disorders occur in affected families compared to control families. Furthermore, the study addressed the impact of sex, year of birth, and degree of urbanization in terms of risk factors. Method A total of N = 746 child and adolescent psychiatric participants born between 1969 and 1986 and registered in the Danish Psychiatric Central Research Register (DPCRR) with a diagnosis of a mental disorder before the age of 18, and developed PHO at some point during their life-time until a maximum age of 40 years were included. In addition, N = 2229 controls without any diagnosis of mental disorders before age 18 and that were matched for age, sex, and residential region were included. Diagnoses of mental disorders were also obtained from the first- degree relatives as a part of the Danish Three Generation Study (3GS). A family load component was obtained by using various mixed regression models. Results PHO occurred significantly more often in case than in control families, in particular, in mothers and siblings. Substance use disorders (SUD), Depressive disorders (DEP), anxiety disorders (ANX) and personality disorders (PERS) in the family were significantly associated with specific phobia in the case-probands. After controlling for various mental disorders comorbid to PHO it was found that some of the family transmission could be caused by various other mental disorders in family members rather than the PHO itself. Female sex and more recent year of birth were further risk factors while region of residence was not related to the manifestation of PHO. Case-relatives did not develop PHO earlier than control relatives. After adjusting for various additional explanatory variables, the family load explained only 0.0013% of the variance in the manifestation of PHO in the case-probands Discussion These findings, based on a very large and representative dataset, provide

  15. A chimeric repressor of petunia PH4 R2R3-MYB family transcription factor generates margined flowers in torenia.

    PubMed

    Kasajima, Ichiro; Sasaki, Katsutomo

    2016-05-01

    The development of new phenotypes is key to the commercial development of the main floricultural species and cultivars. Important new phenotypes include features such as multiple-flowers, color variations, increased flower size, new petal shapes, variegation and distinctive petal margin colourations. Although their commercial use is not yet common, the transgenic technologies provide a potentially rapid means of generating interesting new phenotypes. In this report, we construct 5 vectors which we expected to change the color of the flower anthocyanins, from purple to blue, regulating vacuolar pH. When these constructs were transformed into purple torenia, we unexpectedly recovered some genotypes having slightly margined petals. These transgenic lines expressed a chimeric repressor of the petunia PhPH4 gene under the control of Cauliflower mosaic virus 35 S RNA promoter. PhPH4 is an R2R3-type MYB transcription factor. The transgenic lines lacked pigmentation in the petal margin cells both on the adaxial and abaxial surfaces. Expressions of Flavanone 3-hydroxylase (F3H), Flavonoid 3'-hydroxylase (F3'H) and Flavonoid 3'5'-hydroxylase (F3'5'H) genes were reduced in the margins of these transgenic lines, suggesting an inhibitory effect of PhPH4 repressor on anthocyanin synthesis. PMID:27089475

  16. Dysregulation of the Transforming Growth Factor β Pathway in Induced Pluripotent Stem Cells Generated from Patients with Diamond Blackfan Anemia

    PubMed Central

    Ge, Jingping; Apicella, Marisa; Mills, Jason A.; Garçon, Loïc; French, Deborah L.; Weiss, Mitchell J.; Bessler, Monica; Mason, Philip J.

    2015-01-01

    Diamond Blackfan Anemia (DBA) is an inherited bone marrow failure syndrome with clinical features of red cell aplasia and variable developmental abnormalities. Most affected patients have heterozygous loss of function mutations in ribosomal protein genes but the pathogenic mechanism is still unknown. We generated induced pluripotent stem cells from DBA patients carrying RPS19 or RPL5 mutations. Transcriptome analysis revealed the striking dysregulation of the transforming growth factor β (TGFβ) signaling pathway in DBA lines. Expression of TGFβ target genes, such as TGFBI, BAMBI, COL3A1 and SERPINE1 was significantly increased in the DBA iPSCs. We quantified intermediates in canonical and non-canonical TGFβ pathways and observed a significant increase in the levels of the non-canonical pathway mediator p-JNK in the DBA iPSCs. Moreover, when the mutant cells were corrected by ectopic expression of WT RPS19 or RPL5, levels of p-JNK returned to normal. Surprisingly, nuclear levels of SMAD4, a mediator of canonical TGFβ signaling, were decreased in DBA cells due to increased proteolytic turnover. We also observed the up-regulation of TGFβ1R, TGFβ2, CDKN1A and SERPINE1 mRNA, and the significant decrease of GATA1 mRNA in the primitive multilineage progenitors. In summary our observations identify for the first time a dysregulation of the TGFβ pathway in the pathobiology of DBA. PMID:26258650

  17. Dysregulation of the Transforming Growth Factor β Pathway in Induced Pluripotent Stem Cells Generated from Patients with Diamond Blackfan Anemia.

    PubMed

    Ge, Jingping; Apicella, Marisa; Mills, Jason A; Garçon, Loïc; French, Deborah L; Weiss, Mitchell J; Bessler, Monica; Mason, Philip J

    2015-01-01

    Diamond Blackfan Anemia (DBA) is an inherited bone marrow failure syndrome with clinical features of red cell aplasia and variable developmental abnormalities. Most affected patients have heterozygous loss of function mutations in ribosomal protein genes but the pathogenic mechanism is still unknown. We generated induced pluripotent stem cells from DBA patients carrying RPS19 or RPL5 mutations. Transcriptome analysis revealed the striking dysregulation of the transforming growth factor β (TGFβ) signaling pathway in DBA lines. Expression of TGFβ target genes, such as TGFBI, BAMBI, COL3A1 and SERPINE1 was significantly increased in the DBA iPSCs. We quantified intermediates in canonical and non-canonical TGFβ pathways and observed a significant increase in the levels of the non-canonical pathway mediator p-JNK in the DBA iPSCs. Moreover, when the mutant cells were corrected by ectopic expression of WT RPS19 or RPL5, levels of p-JNK returned to normal. Surprisingly, nuclear levels of SMAD4, a mediator of canonical TGFβ signaling, were decreased in DBA cells due to increased proteolytic turnover. We also observed the up-regulation of TGFβ1R, TGFβ2, CDKN1A and SERPINE1 mRNA, and the significant decrease of GATA1 mRNA in the primitive multilineage progenitors. In summary our observations identify for the first time a dysregulation of the TGFβ pathway in the pathobiology of DBA. PMID:26258650

  18. Consolidative Involved-Node Proton Therapy for Stage IA-IIIB Mediastinal Hodgkin Lymphoma: Preliminary Dosimetric Outcomes From a Phase II Study

    SciTech Connect

    Hoppe, Bradford S.; Flampouri, Stella; Su Zhong; Morris, Christopher G.; Latif, Naeem

    2012-05-01

    Purpose: To compare the dose reduction to organs at risk (OARs) with proton therapy (PT) versus three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) in patients with mediastinal Hodgkin lymphoma (HL) enrolled on a Phase II study of involved-node radiotherapy (INRT). Methods and Materials: Between June 2009 and October 2010, 10 patients were enrolled on a University of Florida institutional review board-approved protocol for de novo 'classical' Stage IA-IIIB HL with mediastinal (bulky or nonbulky) involvement after chemotherapy. INRT was planned per European Organization for Research and Treatment of Cancer guidelines. Three separate optimized plans were developed for each patient: 3D-CRT, IMRT, and PT. The primary end point was a 50% reduction in the body V4 with PT compared with 3D-CRT or IMRT. Results: The median relative reduction with PT in the primary end point, body V4, was 51% compared with 3D-CRT (p = 0.0098) and 59% compared with IMRT (p = 0.0020), thus all patients were offered treatment with PT. PT provided the lowest mean dose to the heart, lungs, and breasts for all 10 patients compared with either 3D-CRT or IMRT. The median difference in the OAR mean dose reduction with PT compared with 3D-CRT were 10.4 Gy/CGE for heart; 5.5 Gy/CGE for lung; 0.9 Gy/CGE for breast; 8.3 Gy/CGE for esophagus; and 4.1 Gy/CGE for thyroid. The median differences for mean OAR dose reduction for PT compared with IMRT were 4.3 Gy/CGE for heart, 3.1 Gy/CGE for lung, 1.4 Gy/CGE for breast, 2.8 Gy/CGE for esophagus, and 2.7 Gy/CGE for thyroid. Conclusions: All 10 patients benefitted from dose reductions to OARs with PT compared with either 3D-CRT or IMRT. It is anticipated that these reductions in dose to OAR will translate into lower rates of late complications, but long-term follow-up on this Phase II INRT study is needed.

  19. Benefits of switching from latanoprost to preservative-free tafluprost eye drops: a meta-analysis of two Phase IIIb clinical trials

    PubMed Central

    Uusitalo, Hannu; Egorov, Evgeniy; Kaarniranta, Kai; Astakhov, Yuri; Ropo, Auli

    2016-01-01

    Introduction Glaucoma patients frequently exhibit ocular surface side effects during treatment with prostaglandin eye drops. The present work investigated whether glaucoma patients suffering from signs and symptoms of ocular surface disease while using preserved latanoprost eye drops benefited from switching to preservative-free tafluprost eye drops. Patients and methods The analysis was based on 339 glaucoma patients enrolled in two Phase IIIb trials. The patients were required to have two symptoms, or one sign and one symptom of ocular surface disease at baseline, and at least 6 months preceding treatment with latanoprost eye drops preserved with benzalkonium chloride. All eligible patients were switched from latanoprost to preservative-free tafluprost for a total of 12 weeks. Ocular symptoms and ocular signs were evaluated at baseline and at 2 weeks, 6 weeks, and 12 weeks after commencing treatment with tafluprost. Intraocular pressure (IOP), drop discomfort, and treatment preference were evaluated to investigate the clinical efficacy and patient-related outcomes. Results After 12 weeks of treatment with preservative-free tafluprost, the incidences of irritation/burning/stinging, foreign body sensation, tearing, itching, and dry eye sensation had diminished to one-third of those reported for preserved latanoprost at baseline. The incidences of blepharitis and corneal/conjunctival fluorescein staining had in turn decreased to one-half of those reported for preserved latanoprost. Severity of conjunctival hyperemia was halved during treatment with preservative-free tafluprost, and there was significant improvement in tear break-up time and tear production. A further reduction in IOP (~1 mmHg) was seen with preservative-free tafluprost compared with preserved latanoprost. Drop discomfort was alleviated during preservative-free tafluprost treatment, and an outstanding majority of patients (72%) preferred preservative-free tafluprost over preserved latanoprost

  20. Second Generation Reusable Launch Vehicle Development and Global Competitiveness of US Space Transportation Industry: Critical Success Factors Assessment

    NASA Technical Reports Server (NTRS)

    Enyinda, Chris I.

    2002-01-01

    In response to the unrelenting call in both public and private sectors fora to reduce the high cost associated with space transportation, many innovative partially or fully RLV (Reusable Launch Vehicles) designs (X-34-37) were initiated. This call is directed at all levels of space missions including scientific, military, and commercial and all aspects of the missions such as nonrecurring development, manufacture, launch, and operations. According to Wertz, tbr over thirty years, the cost of space access has remained exceedingly high. The consensus in the popular press is that to decrease the current astronomical cost of access to space, more safer, reliable, and economically viable second generation RLVs (SGRLV) must be developed. Countries such as Brazil, India, Japan, and Israel are now gearing up to enter the global launch market with their own commercial space launch vehicles. NASA and the US space launch industry cannot afford to lag behind. Developing SGRLVs will immeasurably improve the US's space transportation capabilities by helping the US to regain the global commercial space markets while supporting the transportation capabilities of NASA's space missions, Developing the SGRLVs will provide affordable commercial space transportation that will assure the competitiveness of the US commercial space transportation industry in the 21st century. Commercial space launch systems are having difficulty obtaining financing because of the high cost and risk involved. Access to key financial markets is necessary for commercial space ventures. However, public sector programs in the form of tax incentives and credits, as well as loan guarantees are not yet available. The purpose of this paper is to stimulate discussion and assess the critical success factors germane for RLVs development and US global competitiveness.

  1. Generation of Wheat Transcription Factor FOX Rice Lines and Systematic Screening for Salt and Osmotic Stress Tolerance

    PubMed Central

    Zhang, Qian; Liu, Yayun; Zhu, Butuo; Cao, Jian; Li, Zhanpeng; Han, Longzhi; Jia, Jizeng; Zhao, Guangyao; Sun, Xuehui

    2015-01-01

    Transcription factors (TFs) play important roles in plant growth, development, and responses to environmental stress. In this study, we collected 1,455 full-length (FL) cDNAs of TFs, representing 45 families, from wheat and its relatives Triticum urartu, Aegilops speltoides, Aegilops tauschii, Triticum carthlicum, and Triticum aestivum. More than 15,000 T0 TF FOX (Full-length cDNA Over-eXpressing) rice lines were generated; of these, 10,496 lines set seeds. About 14.88% of the T0 plants showed obvious phenotypic changes. T1 lines (5,232 lines) were screened for salt and osmotic stress tolerance using 150 mM NaCl and 20% (v/v) PEG-4000, respectively. Among them, five lines (591, 746, 1647, 1812, and J4065) showed enhanced salt stress tolerance, five lines (591, 746, 898, 1078, and 1647) showed enhanced osmotic stress tolerance, and three lines (591, 746, and 1647) showed both salt and osmotic stress tolerance. Further analysis of the T-DNA flanking sequences showed that line 746 over-expressed TaEREB1, line 898 over-expressed TabZIPD, and lines 1812 and J4065 over-expressed TaOBF1a and TaOBF1b, respectively. The enhanced salt and osmotic stress tolerance of lines 898 and 1812 was confirmed by retransformation of the respective genes. Our results demonstrate that a heterologous FOX system may be used as an alternative genetic resource for the systematic functional analysis of the wheat genome. PMID:26176782

  2. Complement factor H modulates the activation of human neutrophil granulocytes and the generation of neutrophil extracellular traps.

    PubMed

    Schneider, Andrea E; Sándor, Noémi; Kárpáti, Éva; Józsi, Mihály

    2016-04-01

    Factor H (FH) is a major inhibitor of the alternative pathway of complement activation in plasma and on certain host surfaces. In addition to being a complement regulator, FH can bind to various cells via specific receptors, including binding to neutrophil granulocytes through complement receptor type 3 (CR3; CD11b/CD18), and modulate their function. The cellular roles of FH are, however, poorly understood. Because neutrophils are important innate immune cells in inflammatory processes and the host defense against pathogens, we aimed at studying the effects of FH on various neutrophil functions, including the generation of extracellular traps. FH co-localized with CD11b on the surface of neutrophils isolated from peripheral blood of healthy individuals, and cell-bound FH retained its cofactor activity and enhanced C3b degradation. Soluble FH supported neutrophil migration and immobilized FH induced cell spreading. In addition, immobilized but not soluble FH enhanced IL-8 release from neutrophils. FH alone did not trigger the cells to produce neutrophil extracellular traps (NETs), but NET formation induced by PMA and by fibronectin plus fungal β-glucan were inhibited by immobilized, but not by soluble, FH. Moreover, in parallel with NET formation, immobilized FH also inhibited the production of reactive oxygen species induced by PMA and by fibronectin plus β-glucan. Altogether, these data indicate that FH has multiple regulatory roles on neutrophil functions. While it can support the recruitment of neutrophils, FH may also exert anti-inflammatory effects and influence local inflammatory and antimicrobial reactions, and reduce tissue damage by modulating NET formation. PMID:26938503

  3. New role for Kruppel-like factor 14 as a transcriptional activator involved in the generation of signaling lipids.

    PubMed

    de Assuncao, Thiago M; Lomberk, Gwen; Cao, Sheng; Yaqoob, Usman; Mathison, Angela; Simonetto, Douglas A; Huebert, Robert C; Urrutia, Raul A; Shah, Vijay H

    2014-05-30

    Sphingosine kinase 1 (SK1) is an FGF-inducible gene responsible for generation of sphingosine-1-phosphate, a critical lipid signaling molecule implicated in diverse endothelial cell functions. In this study, we identified SK1 as a target of the canonical FGF2/FGF receptor 1 activation pathway in endothelial cells and sought to identify novel transcriptional pathways that mediate lipid signaling. Studies using the 1.9-kb SK1 promoter and deletion mutants revealed that basal and FGF2-stimulated promoter activity occurred through two GC-rich regions located within 633 bp of the transcription start site. Screening for GC-rich binding transcription factors that could activate this site demonstrated that KLF14, a gene implicated in obesity and the metabolic syndrome, binds to this region. Congruently, overexpression of KLF14 increased basal and FGF2-stimulated SK1 promoter activity by 3-fold, and this effect was abrogated after mutation of the GC-rich sites. In addition, KLF14 siRNA transfection decreased SK1 mRNA and protein levels by 3-fold. Congruently, SK1 mRNA and protein levels were decreased in livers from KLF14 knock-out mice. Combined, luciferase, gel shift, and chromatin immunoprecipitation assays showed that KLF14 couples to p300 to increase the levels of histone marks associated with transcriptional activation (H4K8ac and H3K14ac), while decreasing repressive marks (H3K9me3 and H3K27me3). Collectively, the results demonstrate a novel mechanism whereby SK1 lipid signaling is regulated by epigenetic modifications conferred by KLF14 and p300. Thus, this is the first description of the activity and mechanisms underlying the function of KLF14 as an activator protein and novel regulator of lipid signaling. PMID:24759103

  4. New Role for Kruppel-like Factor 14 as a Transcriptional Activator Involved in the Generation of Signaling Lipids*

    PubMed Central

    de Assuncao, Thiago M.; Lomberk, Gwen; Cao, Sheng; Yaqoob, Usman; Mathison, Angela; Simonetto, Douglas A.; Huebert, Robert C.; Urrutia, Raul A.; Shah, Vijay H.

    2014-01-01

    Sphingosine kinase 1 (SK1) is an FGF-inducible gene responsible for generation of sphingosine-1-phosphate, a critical lipid signaling molecule implicated in diverse endothelial cell functions. In this study, we identified SK1 as a target of the canonical FGF2/FGF receptor 1 activation pathway in endothelial cells and sought to identify novel transcriptional pathways that mediate lipid signaling. Studies using the 1.9-kb SK1 promoter and deletion mutants revealed that basal and FGF2-stimulated promoter activity occurred through two GC-rich regions located within 633 bp of the transcription start site. Screening for GC-rich binding transcription factors that could activate this site demonstrated that KLF14, a gene implicated in obesity and the metabolic syndrome, binds to this region. Congruently, overexpression of KLF14 increased basal and FGF2-stimulated SK1 promoter activity by 3-fold, and this effect was abrogated after mutation of the GC-rich sites. In addition, KLF14 siRNA transfection decreased SK1 mRNA and protein levels by 3-fold. Congruently, SK1 mRNA and protein levels were decreased in livers from KLF14 knock-out mice. Combined, luciferase, gel shift, and chromatin immunoprecipitation assays showed that KLF14 couples to p300 to increase the levels of histone marks associated with transcriptional activation (H4K8ac and H3K14ac), while decreasing repressive marks (H3K9me3 and H3K27me3). Collectively, the results demonstrate a novel mechanism whereby SK1 lipid signaling is regulated by epigenetic modifications conferred by KLF14 and p300. Thus, this is the first description of the activity and mechanisms underlying the function of KLF14 as an activator protein and novel regulator of lipid signaling. PMID:24759103

  5. Application of spatial and non-spatial data analysis in determination of the factors that impact municipal solid waste generation rates in Turkey

    SciTech Connect

    Keser, Saniye; Duzgun, Sebnem; Aksoy, Aysegul

    2012-03-15

    Highlights: Black-Right-Pointing-Pointer Spatial autocorrelation exists in municipal solid waste generation rates for different provinces in Turkey. Black-Right-Pointing-Pointer Traditional non-spatial regression models may not provide sufficient information for better solid waste management. Black-Right-Pointing-Pointer Unemployment rate is a global variable that significantly impacts the waste generation rates in Turkey. Black-Right-Pointing-Pointer Significances of global parameters may diminish at local scale for some provinces. Black-Right-Pointing-Pointer GWR model can be used to create clusters of cities for solid waste management. - Abstract: In studies focusing on the factors that impact solid waste generation habits and rates, the potential spatial dependency in solid waste generation data is not considered in relating the waste generation rates to its determinants. In this study, spatial dependency is taken into account in determination of the significant socio-economic and climatic factors that may be of importance for the municipal solid waste (MSW) generation rates in different provinces of Turkey. Simultaneous spatial autoregression (SAR) and geographically weighted regression (GWR) models are used for the spatial data analyses. Similar to ordinary least squares regression (OLSR), regression coefficients are global in SAR model. In other words, the effect of a given independent variable on a dependent variable is valid for the whole country. Unlike OLSR or SAR, GWR reveals the local impact of a given factor (or independent variable) on the waste generation rates of different provinces. Results show that provinces within closer neighborhoods have similar MSW generation rates. On the other hand, this spatial autocorrelation is not very high for the exploratory variables considered in the study. OLSR and SAR models have similar regression coefficients. GWR is useful to indicate the local determinants of MSW generation rates. GWR model can be utilized to

  6. Factor Analysis of the ESL/EFL Strategy Inventory for Language Learning: Generation 1.5 Korean Immigrant College Students' Language Learning Strategies

    ERIC Educational Resources Information Center

    Heo, Misook; Stoffa, Rosa; Kush, Joseph C.

    2012-01-01

    This study explores factors related to the language learning strategies of second language learners, specifically Generation 1.5 Korean immigrant students--the seventh-largest and one of the fastest growing foreign-born groups in the USA. Participants in this study were members of the Korean communities located in Pittsburgh and Philadelphia who…

  7. The Effect of a Narrative Intervention on Story Retelling and Personal Story Generation Skills of Preschoolers with Risk Factors and Narrative Language Delays

    ERIC Educational Resources Information Center

    Spencer, Trina D.; Slocum, Timothy A.

    2010-01-01

    Narration, or storytelling, is an important aspect of language. Narrative skills have academic and social importance. This study evaluated the effects of a narrative intervention on story retelling and personal story generation skills of preschoolers with risk factors and narrative language delays. Narrative intervention was delivered in a small…

  8. A Chimeric Subunit of Yeast Transcription Factor IIIC Forms a Subcomplex with τ95

    PubMed Central

    Manaud, Nathalie; Arrebola, Rosalía; Buffin-Meyer, Bénédicte; Lefebvre, Olivier; Voss, Hartmut; Riva, Michel; Conesa, Christine; Sentenac, André

    1998-01-01

    The multisubunit yeast transcription factor IIIC (TFIIIC) is a multifunctional protein required for promoter recognition, transcription factor IIIB recruitment, and chromatin antirepression. We report the isolation and characterization of TFC7, an essential gene encoding the 55-kDa polypeptide, τ55, present in affinity-purified TFIIIC. τ55 is a chimeric protein generated by an ancient chromosomal rearrangement. Its C-terminal half is essential for cell viability and sufficient to ensure TFIIIC function in DNA binding and transcription assays. The N-terminal half is nonessential and highly similar to a putative yeast protein encoded on another chromosome and to a cyanobacterial protein of unknown function. Partial deletions of the N-terminal domain impaired τ55 function at a high temperature or in media containing glycerol or ethanol, suggesting a link between PolIII transcription and metabolic pathways. Interestingly, τ55 was found, together with TFIIIC subunit τ95, in a protein complex which was distinct from TFIIIC and which may play a role in the regulation of PolIII transcription, possibly in relation to cell metabolism. PMID:9584160

  9. The importance of family factors and generation status: mental health service use among Latino and Asian Americans.

    PubMed

    Chang, Janet; Natsuaki, Misaki N; Chen, Chih-Nan

    2013-07-01

    The present study utilized data from the National Latino and Asian American Study to examine ethnic and generational differences in family cultural conflict and family cohesion and how the effects of such family conflict and cohesion on lifetime service use vary by generation status for Latino Americans (n = 2,554) and Asian Americans (n = 2,095). Findings revealed that first-generation Asian Americans reported greater family cultural conflict than their Latino counterparts, but third-generation Latino Americans had higher family conflict than their Asian American counterparts. First-generation Latino and Asian Americans had the highest levels of family cohesion. Results from logistic regression analyses indicated that Latino Americans who reported higher family cultural conflict and lower family cohesion were more likely to use mental health services. For Asian Americans, family cultural conflict, but not family cohesion, was associated with service use. Relative to third-generation Asian Americans, second-generation Asian Americans with higher family cultural conflict were more likely to use mental health services. Given that cohesive familial bonds appear to discourage service use on the part of Latino Americans irrespective of generation status, further research is needed to ascertain the extent to which this tendency stems from greater reliance on family support as opposed to the stigma associated with mental health treatment. Mental health providers and treatment programs need to address the role of family cultural conflict in the lives of Asian Americans, particularly second generation, and Latino Americans across generations, because conflictual family ties may motivate help-seeking behaviors and reveal substantial underlying distress.

  10. Human factors engineering control-room-design review/audit report: Palo Verde Nuclear Generating Station, Arizona Public Service Company

    SciTech Connect

    Savage, J.W.; Lappa, D.A.

    1981-10-09

    A human factors engineering design review of the Palo Verde control room simulator was performed at the site on September 15 through September 17, 1981. Observed human factors design discrepancies were given priority ratings. This report summarizes the team's observations of the control room design and layout and of the control room operators' interface with the control room environment. A list of the human factors strengths observed in the Palo Verde control room simulator is given.

  11. Prediction of household and commercial BMW generation according to socio-economic and other factors for the Dublin region.

    PubMed

    Purcell, M; Magette, W L

    2009-04-01

    Both planning and design of integrated municipal solid waste management systems require accurate prediction of waste generation. This research predicted the quantity and distribution of biodegradable municipal waste (BMW) generation within a diverse 'landscape' of residential areas, as well as from a variety of commercial establishments (restaurants, hotels, hospitals, etc.) in the Dublin (Ireland) region. Socio-economic variables, housing types, and the sizes and main activities of commercial establishments were hypothesized as the key determinants contributing to the spatial variability of BMW generation. A geographical information system (GIS) 'model' of BMW generation was created using ArcMap, a component of ArcGIS 9. Statistical data including socio-economic status and household size were mapped on an electoral district basis. Historical research and data from scientific literature were used to assign BMW generation rates to residential and commercial establishments. These predictions were combined to give overall BMW estimates for the region, which can aid waste planning and policy decisions. This technique will also aid the design of future waste management strategies, leading to policy and practice alterations as a function of demographic changes and development. The household prediction technique gave a more accurate overall estimate of household waste generation than did the social class technique. Both techniques produced estimates that differed from the reported local authority data; however, given that local authority reported figures for the region are below the national average, with some of the waste generated from apartment complexes being reported as commercial waste, predictions arising from this research are believed to be closer to actual waste generation than a comparison to reported data would suggest. By changing the input data, this estimation tool can be adapted for use in other locations. Although focusing on waste in the Dublin region

  12. Prediction of household and commercial BMW generation according to socio-economic and other factors for the Dublin region.

    PubMed

    Purcell, M; Magette, W L

    2009-04-01

    Both planning and design of integrated municipal solid waste management systems require accurate prediction of waste generation. This research predicted the quantity and distribution of biodegradable municipal waste (BMW) generation within a diverse 'landscape' of residential areas, as well as from a variety of commercial establishments (restaurants, hotels, hospitals, etc.) in the Dublin (Ireland) region. Socio-economic variables, housing types, and the sizes and main activities of commercial establishments were hypothesized as the key determinants contributing to the spatial variability of BMW generation. A geographical information system (GIS) 'model' of BMW generation was created using ArcMap, a component of ArcGIS 9. Statistical data including socio-economic status and household size were mapped on an electoral district basis. Historical research and data from scientific literature were used to assign BMW generation rates to residential and commercial establishments. These predictions were combined to give overall BMW estimates for the region, which can aid waste planning and policy decisions. This technique will also aid the design of future waste management strategies, leading to policy and practice alterations as a function of demographic changes and development. The household prediction technique gave a more accurate overall estimate of household waste generation than did the social class technique. Both techniques produced estimates that differed from the reported local authority data; however, given that local authority reported figures for the region are below the national average, with some of the waste generated from apartment complexes being reported as commercial waste, predictions arising from this research are believed to be closer to actual waste generation than a comparison to reported data would suggest. By changing the input data, this estimation tool can be adapted for use in other locations. Although focusing on waste in the Dublin region

  13. Shared Genetic Aetiology between Cognitive Ability and Cardiovascular Disease Risk Factors: Generation Scotland's Scottish Family Health Study

    ERIC Educational Resources Information Center

    Luciano, Michelle; Batty, G. David; McGilchrist, Mark; Linksted, Pamela; Fitzpatrick, Bridie; Jackson, Cathy; Pattie, Alison; Dominiczak, Anna F.; Morris, Andrew D.; Smith, Blair H.; Porteous, David; Deary, Ian J.

    2010-01-01

    People with higher general cognitive ability in early life have more favourable levels of cardiovascular disease (CVD) risk factors in adulthood and CVD itself. The mechanism of these associations is not known. Here we examine whether general cognitive ability and CVD risk factors share genetic and/or environmental aetiology. In this large,…

  14. Contributing Factors to Generation 1.5 Students' Successes on the Exit State Assessment for High School

    ERIC Educational Resources Information Center

    Vanderhoef, Deborah E.

    2012-01-01

    This phenomenological narrative study investigated the successes of eight Generation 1.5 high school seniors on the Exit state assessment in English language arts in Texas. These eight participants represented three difficult ethnic cultures, Hispanic, Pakistani and Turkish; within the Hispanic cultures the countries of Mexico and El Salvador were…

  15. Technique for information retrieval using enhanced latent semantic analysis generating rank approximation matrix by factorizing the weighted morpheme-by-document matrix

    DOEpatents

    Chew, Peter A; Bader, Brett W

    2012-10-16

    A technique for information retrieval includes parsing a corpus to identify a number of wordform instances within each document of the corpus. A weighted morpheme-by-document matrix is generated based at least in part on the number of wordform instances within each document of the corpus and based at least in part on a weighting function. The weighted morpheme-by-document matrix separately enumerates instances of stems and affixes. Additionally or alternatively, a term-by-term alignment matrix may be generated based at least in part on the number of wordform instances within each document of the corpus. At least one lower rank approximation matrix is generated by factorizing the weighted morpheme-by-document matrix and/or the term-by-term alignment matrix.

  16. Efficient generation of integration-free ips cells from human adult peripheral blood using BCL-XL together with Yamanaka factors.

    PubMed

    Su, Rui-Jun; Baylink, David J; Neises, Amanda; Kiroyan, Jason B; Meng, Xianmei; Payne, Kimberly J; Tschudy-Seney, Benjamin; Duan, Yuyou; Appleby, Nancy; Kearns-Jonker, Mary; Gridley, Daila S; Wang, Jun; Lau, K-H William; Zhang, Xiao-Bing

    2013-01-01

    The ability to efficiently generate integration-free induced pluripotent stem cells (iPSCs) from the most readily available source-peripheral blood-has the potential to expedite the advances of iPSC-based therapies. We have successfully generated integration-free iPSCs from cord blood (CB) CD34(+) cells with improved oriP/EBNA1-based episomal vectors (EV) using a strong spleen focus forming virus (SFFV) long terminal repeat (LTR) promoter. Here we show that Yamanaka factors (OCT4, SOX2, MYC, and KLF4)-expressing EV can also reprogram adult peripheral blood mononuclear cells (PBMNCs) into pluripotency, yet at a very low efficiency. We found that inclusion of BCL-XL increases the reprogramming efficiency by approximately 10-fold. Furthermore, culture of CD3(-)/CD19(-) cells or T/B cell-depleted MNCs for 4-6 days led to the generation of 20-30 iPSC colonies from 1 ml PB, an efficiency that is substantially higher than previously reported. PB iPSCs express pluripotency markers, form teratomas, and can be induced to differentiate in vitro into mesenchymal stem cells, cardiomyocytes, and hepatocytes. Used together, our optimized factor combination and reprogramming strategy lead to efficient generation of integration-free iPSCs from adult PB. This discovery has potential applications in iPSC banking, disease modeling and regenerative medicine.

  17. Sodium arsenite induced reactive oxygen species generation, nuclear factor (erythroid-2 related) factor 2 activation, heme oxygenase-1 expression, and glutathione elevation in Chang human hepatocytes.

    PubMed

    Li, Bing; Li, Xin; Zhu, Bo; Zhang, Xinyu; Wang, Yi; Xu, Yuanyuan; Wang, Huihui; Hou, Yongyong; Zheng, Quanmei; Sun, Guifan

    2013-07-01

    Liver is one of the major target organs of arsenic toxicity and carcinogenesis. Nuclear factor (erythroid-2 related) factor 2 (Nrf2) is a redox-sensitive transcription factor, regulating critically cellular defense responses against the toxic metallic arsenic in many cell types and tissues. This study was conducted to evaluate the hepato-cellular Nrf2 and Nrf2-regulated antioxidant reactions of sodium arsenite exposure in Chang human hepatocytes. Nrf2 and heme oxygenase-1 (HO-1) protein levels were detected by Western blot, and Nrf2-regulated HO-1 mRNA expressions were determined using semiquantitative RT-PCR by 0∼50 μmol/L of sodium arsenite exposure for 2, 6, 12, and 24 h. We also observed the changes of intracellular reactive oxygen species (ROS) and total cellular glutathione (GSH) by flow cytometry and spectrophotometry, respectively. Our results showed that intracellular ROS were both dose- and time-dependent induced by inorganic arsenic; Cellular Nrf2 protein levels increased rapidly after 2 h of exposure, elevated significantly at 6 h, and reached the maximum at 12 h. The endogenous Nrf2-regulated downstream HO-1 mRNA and protein were also induced dramatically and lasted for as long as 24 h. In addition, intracellular GSH levels elevated in consistent with Nrf2 activation. Our findings here suggest that inorganic arsenic alters cellular redox balance in hepatocytes to trigger Nrf2-regulated antioxidant responses promptly, which may represent an adaptive cell defense mechanism against inorganic arsenic induced liver injuries and hepatoxicity.

  18. Theoretical exploration of control factors for the high-order harmonic generation (HHG) spectrum in two-color field.

    PubMed

    Huang, Xinting; Yang, Dapeng; Yao, Li

    2014-09-15

    In this work, the laser-parameter effects on the high-order harmonic generation (HHG) spectrum and attosecond trains by mixing two-color laser field, a visible light field of 800 nm and a mid-infrared (mid-IR) laser pulses of 2400 nm, are theoretically demonstrated for the first time. Different schemes are applied to discuss the function of intensity, carrier-envelope phase (CEP) and pulse duration on the generation of an isolated attosecond pulse. As a consequence, an isolated 16as pulse is obtained by Fourier transforming an ultrabroad XUV continuum of 208 eV with the fundamental field of duration of 6 fs, 9×10(14)W/cm2 of intensity, the duration of 12 fs, the CEPs of the two driving pulses of -π and the relative strength ratio √R=0.2. PMID:24759780

  19. Theoretical exploration of control factors for the high-order harmonic generation (HHG) spectrum in two-color field.

    PubMed

    Huang, Xinting; Yang, Dapeng; Yao, Li

    2014-09-15

    In this work, the laser-parameter effects on the high-order harmonic generation (HHG) spectrum and attosecond trains by mixing two-color laser field, a visible light field of 800 nm and a mid-infrared (mid-IR) laser pulses of 2400 nm, are theoretically demonstrated for the first time. Different schemes are applied to discuss the function of intensity, carrier-envelope phase (CEP) and pulse duration on the generation of an isolated attosecond pulse. As a consequence, an isolated 16as pulse is obtained by Fourier transforming an ultrabroad XUV continuum of 208 eV with the fundamental field of duration of 6 fs, 9×10(14)W/cm2 of intensity, the duration of 12 fs, the CEPs of the two driving pulses of -π and the relative strength ratio √R=0.2.

  20. Three-loop radiative-recoil corrections to hyperfine splitting generated by one-loop fermion factors

    SciTech Connect

    Eides, Michael I.; Grotch, Howard; Shelyuto, Valery A.

    2004-10-01

    We consider three-loop radiative-recoil corrections to hyperfine splitting in muonium generated by diagrams with one-loop radiative photon insertions both in the electron and muon lines. An analytic result for these nonlogarithmic corrections of order {alpha}(Z{sup 2}{alpha})(Z{alpha})(m/M)E{sub F} is obtained. This result constitutes a next step in the implementation of the program of reduction of the theoretical uncertainty of hyperfine splitting below 10 Hz.

  1. [Analysis of the risk factors for severe neutropenia in advanced non-small cell lung cancer after the first course of chemotherapy with third-generation agents].

    PubMed

    Shibuya, Midori; Kogo, Mari; Kurihara, Tatsuya; Shikama, Yusuke; Nakajima, Hiroaki; Yoneyama, Keiichiro; Kiuchi, Yuji

    2013-01-01

      We retrospectively evaluated clinical data before therapy to determine the risk factors for severe neutropenia in advanced non-small-cell lung cancer (NSCLC) patients treated with third-generation agents. We analyzed 100 patients who received such agents (paclitaxel, docetaxel, gemcitabine, irinotecan, or vinorelbine) for advanced NSCLC. The endpoint of the survey was the occurrence of severe neutropenia (grade 4). Risk factors significantly related to severe neutropenia were identified using logistic regression analysis. Of the 100 patients studied, the median age was 62.0 (32-81 years), and 77 (77.0%) were male. CEA 6.6 (0-2220) ng/dL and cytokeratin 19 fragment 21-1 (CYFRA) 4.8 (0.2-173.8) ng/dL before chemotherapy were higher than normal range. Severe neutropenia occurred in 36.0%, the incidence being highest in the first cycle (61.1%). In the univariate analysis, variables associated with severe neutropenia were sex, chest pain, absolute neutrophil count (ANC), Cr, CRP, and CYFRA. In the multivariate analysis, low CYFRA level was identified as a significant risk factor that contributed independently to chemotherapy-induced severe neutropenia (p<0.05). Our analysis suggests that low CYFRA level is the most important risk factor for severe neutropenia in advanced NSCLC patients after the first course of chemotherapy with third-generation agents. PMID:23728094

  2. Factor Xa generation at the surface of cultured rat vascular smooth muscle cells in an in vitro flow system.

    PubMed

    Hall, C L; Taubman, M B; Nemerson, Y; Turitto, V T

    1998-08-01

    The purpose of the present investigation was to explore the effects of well-defined flow conditions on the activity of tissue factor (TF) expressed on the surface of cultured rat vascular smooth muscle cells. Cells were cultured to confluence on Permanox brand slides and stimulated to express TF by a 90 min incubation with fresh growth medium containing 10 percent calf serum. The stimulated cells were then placed in a parallel plate flow chamber and perfused with Hank's Balanced Salt Solution containing factor VIIa, factor X (FX), and calcium. The chamber effluent was collected and assayed for factor Xa (FXa) and the steady-state flux of FXa was calculated. The flux values were 68.73, 94.81, 139.75, 138.19, 316.82, and 592.92 fmole/min/cm2 at wall shear rates of 10, 20, 40, 80, 320, and 1280 s-1, respectively. The FXa flux depended on the wall shear rate to a greater degree than predicted by classical mass transport theory. The flux at each shear rate was three to five times less than that calculated according to the Leveque solution. These features of the experimental data imply nonclassical behavior, which may partially result from a direct effect of flow on the cell layer.

  3. Human factors in the presentation of computer-generated information - Aspects of design and application in automated flight traffic

    NASA Technical Reports Server (NTRS)

    Roske-Hofstrand, Renate J.

    1990-01-01

    The man-machine interface and its influence on the characteristics of computer displays in automated air traffic is discussed. The graphical presentation of spatial relationships and the problems it poses for air traffic control, and the solution of such problems are addressed. Psychological factors involved in the man-machine interface are stressed.

  4. Immigrant Parents' Choice of a Bilingual versus Monolingual Kindergarten for Second-Generation Children: Motives, Attitudes, and Factors

    ERIC Educational Resources Information Center

    Schwartz, Mila; Moin, Victor; Leikin, Mark; Breitkopf, Anna

    2010-01-01

    This study investigated how immigrant parents describe and explain their family language policy concerning their child's preschool bilingual development, and also explored the factors linked to the parents' choice of bilingual or monolingual kindergarten for their child. The study design was based on a comparison of 2 groups of parents: those who…

  5. Differential effects of glucose and alcohol on reactive oxygen species generation and intranuclear nuclear factor-kappaB in mononuclear cells.

    PubMed

    Dhindsa, Sandeep; Tripathy, Devjit; Mohanty, Priya; Ghanim, Husam; Syed, Tufail; Aljada, Ahmad; Dandona, Paresh

    2004-03-01

    It has previously been shown that oral intake of 300 calories of glucose (75 g), lipid, or protein increases reactive oxygen species (ROS) generation by polymorphonuclear cells (PMNL) and mononuclear cells (MNCs). We investigated the effects of 75 g glucose on proinflammatory transcription factor, nuclear factor-kappaB (NFkappaB), in mononuclear cells. To further investigate whether the effects of macronutrient-induced oxidative stress are due to consumption of calories or are nutrient specific, we investigated the effects of acute oral challenge of equicaloric amounts of alcohol (300 calories) on ROS generation and NF-kappaB activation in MNCs and PMNL and compared them with those of glucose and water (control). Sixteen normal healthy adult volunteers were given either vodka (10 subjects), glucose solution (10 subjects), or 300 mL water (7 subjects). Vodka and glucose drinks were equivalent to 300 calories. We measured ROS generation and intranuclear NF-kappaB activation by PMNL cells and MNCs at 1 hour, 2 hours, and 3 hours following ingestion. ROS generation by both MNC and PMNL increased significantly (P <.05 for MNC and P <.01 for PMNL) following intake of glucose solution, but did not change significantly following alcohol or water. NF-kappaB binding activity in MNC nuclear extracts also increased (P <.001) following ingestion of glucose solution, but did not change after the administration of alcohol or water. We conclude that (1) 75 g oral glucose increases NF-kappaB binding activity in MNCs. (2) While 75 g glucose (300 calories) induces an increase in ROS generation and intranuclear NF-kappaB, equicaloric amounts of alcohol did not produce these effects.

  6. Generation of reactive oxygen species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate

    SciTech Connect

    Arana, Lide; Gangoiti, Patricia; Ouro, Alberto; Rivera, Io-Guane; Ordonez, Marta; Trueba, Miguel; Lankalapalli, Ravi S.; Bittman, Robert; Gomez-Munoz, Antonio

    2012-02-15

    We previously demonstrated that ceramide 1-phosphate (C1P) is mitogenic for fibroblasts and macrophages. However, the mechanisms involved in this action were only partially described. Here, we demonstrate that C1P stimulates reactive oxygen species (ROS) formation in primary bone marrow-derived macrophages, and that ROS are required for the mitogenic effect of C1P. ROS production was dependent upon prior activation of NADPH oxidase by C1P, which was determined by measuring phosphorylation of the p40phox subunit and translocation of p47phox from the cytosol to the plasma membrane. In addition, C1P activated cytosolic calcium-dependent phospholipase A{sub 2} and protein kinase C-{alpha}, and NADPH oxidase activation was blocked by selective inhibitors of these enzymes. These inhibitors, and inhibitors of ROS production, blocked the mitogenic effect of C1P. By using BHNB-C1P (a photolabile caged-C1P analog), we demonstrate that all of these C1P actions are caused by intracellular C1P. It can be concluded that the enzyme responsible for C1P-stimulated ROS generation in bone marrow-derived macrophages is NADPH oxidase, and that this enzyme is downstream of PKC-{alpha} and cPLA{sub 2}-{alpha} in this pathway. -- Highlights: Black-Right-Pointing-Pointer Ceramide 1-phosphate (C1P) stimulates reactive oxygen species (ROS) formation. Black-Right-Pointing-Pointer The enzyme responsible for ROS generation by C1P in macrophages is NADPH oxidase. Black-Right-Pointing-Pointer NADPH oxidase lies downstream of cPLA{sub 2}-{alpha} and PKC-{alpha} in this pathway. Black-Right-Pointing-Pointer ROS generation is essential for the stimulation of macrophage proliferation by C1P.

  7. Monitoring Low Molecular Weight Heparins at Therapeutic Levels: Dose-Responses of, and Correlations and Differences between aPTT, Anti-Factor Xa and Thrombin Generation Assays

    PubMed Central

    Thomas, Owain; Lybeck, Emanuel; Strandberg, Karin; Tynngård, Nahreen; Schött, Ulf

    2015-01-01

    Background Low molecular weight heparins (LMWH’s) are used to prevent and treat thrombosis. Tests for monitoring LMWH’s include anti-factor Xa (anti-FXa), activated partial thromboplastin time (aPTT) and thrombin generation. Anti-FXa is the current gold standard despite LMWH’s varying affinities for FXa and thrombin. Aim To examine the effects of two different LMWH’s on the results of 4 different aPTT-tests, anti-FXa activity and thrombin generation and to assess the tests’ concordance. Method Enoxaparin and tinzaparin were added ex-vivo in concentrations of 0.0, 0.5, 1.0 and 1.5 anti-FXa international units (IU)/mL, to blood from 10 volunteers. aPTT was measured using two whole blood methods (Free oscillation rheometry (FOR) and Hemochron Jr (HCJ)) and an optical plasma method using two different reagents (ActinFSL and PTT-Automat). Anti-FXa activity was quantified using a chromogenic assay. Thrombin generation (Endogenous Thrombin Potential, ETP) was measured on a Ceveron Alpha instrument using the TGA RB and more tissue-factor rich TGA RC reagents. Results Methods’ mean aPTT at 1.0 IU/mL LMWH varied between 54s (SD 11) and 69s (SD 14) for enoxaparin and between 101s (SD 21) and 140s (SD 28) for tinzaparin. ActinFSL gave significantly shorter aPTT results. aPTT and anti-FXa generally correlated well. ETP as measured with the TGA RC reagent but not the TGA RB reagent showed an inverse exponential relationship to the concentration of LMWH. The HCJ-aPTT results had the weakest correlation to anti-FXa and thrombin generation (Rs0.62–0.87), whereas the other aPTT methods had similar correlation coefficients (Rs0.80–0.92). Conclusions aPTT displays a linear dose-respone to LMWH. There is variation between aPTT assays. Tinzaparin increases aPTT and decreases thrombin generation more than enoxaparin at any given level of anti-FXa activity, casting doubt on anti-FXa’s present gold standard status. Thrombin generation with tissue factor-rich activator is

  8. Wind Generators

    NASA Astrophysics Data System (ADS)

    1989-01-01

    When Enerpro, Inc. president, Frank J. Bourbeau, attempted to file a patent on a system for synchronizing a wind generator to the electric utility grid, he discovered Marshall Space Flight Center's Frank Nola's power factor controller. Bourbeau advanced the technology and received a NASA license and a patent for his Auto Synchronous Controller (ASC). The ASC reduces generator "inrush current," which occurs when large generators are abruptly brought on line. It controls voltage so the generator is smoothly connected to the utility grid when it reaches its synchronous speed, protecting the components from inrush current damage. Generator efficiency is also increased in light winds by applying lower than rated voltage. Wind energy is utilized to drive turbines to generate electricity for utility companies.

  9. Identification of caveolin-1 as a potential causative factor in the generation of trastuzumab resistance in breast cancer cells.

    PubMed

    Sekhar, Sreeja C; Kasai, Tomonari; Satoh, Ayano; Shigehiro, Tsukasa; Mizutani, Akifumi; Murakami, Hiroshi; El-Aarag, Bishoy Ya; Salomon, David S; Massaguer, Anna; de Llorens, Rafael; Seno, Masaharu

    2013-01-01

    The oncogenic tyrosine kinase receptor ErbB2 is a prognostic factor and target for breast cancer therapeutics. In contrast with the other ErbB receptors, ErbB2 is hardly internalized by ligand induced mechanisms, indicating a prevalent surface expression. Elevated levels of ErbB2 in tumor cells are associated with its defective endocytosis and down regulation. Here we show that caveolin-1 expression in breast cancer derived SKBR-3 cells (SKBR-3/Cav-1) facilitates ligand induced ErbB2 endocytosis using an artificial peptide ligand EC-eGFP. Similarly, stimulation with humanized anti ErbB2 antibody Trastuzumab (Herceptin) was found to be internalized and co-localized with caveolin-1 in SKBR-3/Cav-1 cells. Internalized EC-eGFP and Trastuzumab in SKBR-3/Cav-1 cells were then delivered via caveolae to the caveolin-1 containing early endosomes. Consequently, attenuated Fc receptor mediated ADCC functions were observed when exposed to Trastuzumab and EC-Fc (EC-1 peptide conjugated to Fc part of human IgG). On the other hand, this caveolae dependent endocytic synergy was not observed in parental SKBR-3 cells. Therefore, caveolin-1 expression in breast cancer cells could be a predictive factor to estimate how cancer cells are likely to respond to Trastuzumab treatment. PMID:23833684

  10. Modifications of human growth differentiation factor 9 to improve the generation of embryos from low competence oocytes.

    PubMed

    Li, Jing-Jie; Sugimura, Satoshi; Mueller, Thomas D; White, Melissa A; Martin, Georgia A; Ritter, Lesley J; Liang, Xiao-Yan; Gilchrist, Robert B; Mottershead, David G

    2015-01-01

    Growth differentiation factor 9 (GDF9) is an oocyte-derived growth factor that plays a critical role in ovarian folliculogenesis and oocyte developmental competence and belongs to the TGF-β family of proteins. Recombinant human GDF9 (hGDF9) is secreted in a latent form, which in the case of the fully processed protein, has the proregion noncovalently associated with the mature region. In this study, we investigated a number of amino acid residues in the mature region of hGDF9 that are different from the corresponding residues in the mouse protein, which is not latent. We designed, expressed, and purified 4 forms of chimeric hGDF9 (M1-M4) that we found to be active in a granulosa cell bioassay. Using a porcine in vitro maturation model with inherent low developmental competence (yielding 10%-20% blastocysts), we tested the ability of the chimeric hGDF9 proteins to improve oocyte maturation and developmental competence. Interestingly, one of the chimeric proteins, M3, was able to significantly increase the level of embryo production using such low competence oocytes. Our molecular modeling studies suggest that in the case of hGDF9 the Gly(391)Arg mutation probably increases receptor binding affinity, thereby creating an active protein for granulosa cells in vitro. However, for an improvement in oocyte developmental competence, a second mutation (Ser(412)Pro), which potentially decreases the affinity of the mature region for the proregion, is also required. PMID:25394262

  11. Use of mice tolerant to lipopolysaccharide to demonstrate requirement of cooperation between macrophages and lymphocytes to generate lipopolysaccharide-induced colony-stimulating factor in vivo.

    PubMed Central

    Williams, Z; Hertogs, C F; Pluznik, D H

    1983-01-01

    Injection of lipopolysaccharide (LPS) into mice was followed by a rapid elevation of colony-stimulating factor (CSF) in the serum. A second, challenging injection of LPS given 3 to 4 days later failed to induce elevated levels of CSF in the serum. Such mice tolerant to LPS were used as an experimental tool to identify the CSF-producing cells which respond to LPS. We observed that generation of LPS-induced CSF in mice tolerant to LPS could be restored by an intraperitoneal injection of spleen cells 24 h before the challenging injection of LPS. Depletion of the adherent cells from the spleen cells reduced the ability of the splenic lymphocytes to restore the capacity of the mice tolerant to LPS to generate serum CSF. Reconstitution of the splenic lymphocytes with 5% thioglycolate-elicited peritoneal macrophages, however, reestablished the restorative capacity of these cells, whereas almost no restoration was observed after direct injection of elicited peritoneal macrophages. These data suggest that the spleen cells are active in generating CSF, provided that macrophages are present and can interact with the splenic lymphocytes to generate LPS-induced CSF in the serum. PMID:6602767

  12. Second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs): a better mousetrap? A review of the clinical evidence.

    PubMed

    Ou, Sai-Hong Ignatius

    2012-09-01

    The discovery of activating epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) in 2004 heralded the era of molecular targeted therapy in NSCLC. First-generation small molecule, reversible tyrosine kinase inhibitors (TKIs) of EGFR, gefitinib and erlotinib, had been approved for second- or third-line treatment of NSCLC prior to the knowledge of these mutations. However, resistance to gefitinib and erlotinib invariably develops after prolonged clinical use. Two second-generation irreversible EGFR TKIs, afatinib (BIBW 2992) and dacomitinib (PF-00299804), that can potentially overcome the majority of these resistances are in late stage clinical development. Here I will review the clinical data of EGFR TKIs and discuss the appropriate future role of afatinib and dacomitinib in NSCLC: whether as replacement of erlotinib or gefitinib or only after erlotinib or gefitinib failure and whether different subgroups would benefit from different approaches.

  13. Factors influencing storm-generated suspended-sediment concentrations and loads in four basins of contrasting land use, humid-tropical Puerto Rico

    USGS Publications Warehouse

    Gellis, Allen C.

    2013-01-01

    The significant characteristics controlling the variability in storm-generated suspended-sediment loads and concentrations were analyzed for four basins of differing land use (forest, pasture, cropland, and urbanizing) in humid-tropical Puerto Rico. Statistical analysis involved stepwise regression on factor scores. The explanatory variables were attributes of flow, hydrograph peaks, and rainfall, categorized into 5 flow periods: (1) the current storm hydrograph, (2) the flow and rainfall since the previous storm event, (3) the previous storm event, (4) 2nd previous storm event, and (5) the 3rd previous storm event. The response variables (storm generated sediment loads and concentrations) were analyzed for three portions of the storm hydrograph: (1) the entire storm, (2) the rising limb, and (3) the recessional limb. Hysteresis differences in sediment concentration between the rising and falling limb were also analyzed using these explanatory variables.

  14. SU-E-P-15: Technique Factor Modulation and Reference Plane Air Kerma Rates in Response to Simulated Patient Thickness Variations for a Sample of Current Generation Fluoroscopes

    SciTech Connect

    Wunderle, K; Rakowski, J; Dong, F

    2015-06-15

    Purpose: To evaluate and compare approaches to technique factor modulation and air kerma rates in response to simulated patient thickness variations for four state-of-the-art and one previous-generation interventional fluoroscopes. Methods: A polymethyl methacrylate (PMMA) phantom was used as a tissue surrogate for the purposes of determining fluoroscopic reference plane air kerma rates, kVp, mA, and spectral filtration over a wide range of simulated tissue thicknesses. Data were acquired for each fluoroscopic and acquisition dose curve within a default abdomen or body imaging protocol. Results: The data obtained indicated vendor- and model-specific variations in the approach to technique factor modulation and reference plane air kerma rates across a range of tissue thicknesses. Some vendors have made hardware advances increasing the radiation output capabilities of their fluoroscopes; this was evident in the acquisition air kerma rates. However, in the imaging protocol evaluated, all of the state-of-the-art systems had relatively low air kerma rates in the fluoroscopic low-dose imaging mode as compared to the previous-generation unit. Each of the newest-generation systems also employ copper filtration in the selected protocol in the acquisition mode of imaging; this is a substantial benefit, reducing the skin entrance dose to the patient in the highest dose-rate mode of fluoroscope operation. Conclusion: Understanding how fluoroscopic technique factors are modulated provides insight into the vendor-specific image acquisition approach and provides opportunities to optimize the imaging protocols for clinical practice. The enhanced radiation output capabilities of some of the fluoroscopes may, under specific conditions, may be beneficial; however, these higher output capabilities also have the potential to lead to unnecessarily high dose rates. Therefore, all parties involved in imaging, including the clinical team, medical physicists, and imaging vendors, must work

  15. [Predict factors associated with malnutrition from patient generated subjective global assessment (PG-SGA) in head and neck cancer patients].

    PubMed

    Arribas, L; Hurtós, L; Milà, R; Fort, E; Peiró, I

    2013-01-01

    Introducción: La valoración global subjetiva generada por el paciente (VGS-GP) es una herramienta validada para la valoración nutricional de los pacientes oncológicos. Objetivo: El objetivo de nuestro estudio es conocer la prevalencia de desnutrición de los pacientes con cáncer de cabeza y cuello en el momento del diagnóstico y evaluar los factores pronósticos independientes de desnutrición a partir de la VGS-GP. Material y métodos: Todos los pacientes ambulatorios que fueron evaluados por el Comité de Tumores de Cabeza y Cuello para diagnóstico primario, estadiaje y decisión terapéutica fueron evaluados a través de la VGSGP. Se excluyeron recidivas tumorales y segundas neoplasias. Resultados: Se evaluaron 64 pacientes (55 hombres y 9 mujeres) con una edad media de 63 2013s y un índice de masa corporal (IMC) de 25,3 kg/m(2). Después de realizar la VGS-GP se observó que el 43,8% presentaban desnutrición o riesgo de padecerla. Los síntomas más frecuentes en el momento del diagnóstico fueron la disfagia (48,4%) y la anorexia (26.6%). Dentro de la VGS-GP, los principales factores pronósticos (p<0,001) fueron el porcentaje de pérdida de peso, los niveles de albúmina, el valor del IMC y la presencia de disfagia y/o anorexia. Conclusiones: Parámetros como el IMC, la pérdida de peso y las cifras de albúmina en el momento del diagnóstico de cáncer de cabeza y cuello, son factores predictivos independientes para el diagnóstico de desnutrición, así como la presencia de anorexia o disfagia.

  16. Challenges of the management of severe hemophilia A with inhibitors: two case reports emphasizing the potential interest of a high-purity human Factor VIII/von Willebrand factor concentrate and individually tailored prophylaxis guided by thrombin-generation test.

    PubMed

    Mathieu, Sophie; Crampe, Carine; Dargaud, Yesim; Lavigne-Lissalde, Géraldine; Escuriola-Ettingshausen, Carmen; Tardy, Brigitte; Meley, Roland; Thouvenin, Sandrine; Stephan, Jean L; Berger, Claire

    2015-12-01

    Severe hemophilia A is an X-linked bleeding disorder. Immune tolerance induction (ITI) is the best strategy of treatment when patients develop inhibitors. The objective is to illustrate the benefit of a high-purity human factor VIII/von Willebrand factor (VWF) concentrate (Octanate) in the management of ITI. We also wanted to raise the potential interest of laboratory assays such as thrombin-generation test (TGT) and epitope mapping. Two patients were treated during ITI, first with a recombinant FVIII and then with plasma-derived factor VIII without success, and, finally, with Octanate. Bypassing agents were used based on the results of TGT. Epitope mapping was performed during ITI therapy. These observations suggest the potential contribution of Octanate in the management of ITI in difficult cases. The use of bypassing agents can be necessary in prophylaxis or to treat bleedings, and may be guided by TGT results. Epitope mapping is used to describe the inhibitor. This article shows a decrease of the inhibitor directed against the C2 domain after initiation of Octanate. A high-purity human factor VIII/von Willebrand factor concentrate (Octanate) may be a valuable therapeutical option for ITI therapy. TGT and epitope mapping could be of help in the management of ITI.

  17. Challenges of the management of severe hemophilia A with inhibitors: two case reports emphasizing the potential interest of a high-purity human Factor VIII/von Willebrand factor concentrate and individually tailored prophylaxis guided by thrombin-generation test.

    PubMed

    Mathieu, Sophie; Crampe, Carine; Dargaud, Yesim; Lavigne-Lissalde, Géraldine; Escuriola-Ettingshausen, Carmen; Tardy, Brigitte; Meley, Roland; Thouvenin, Sandrine; Stephan, Jean L; Berger, Claire

    2015-12-01

    Severe hemophilia A is an X-linked bleeding disorder. Immune tolerance induction (ITI) is the best strategy of treatment when patients develop inhibitors. The objective is to illustrate the benefit of a high-purity human factor VIII/von Willebrand factor (VWF) concentrate (Octanate) in the management of ITI. We also wanted to raise the potential interest of laboratory assays such as thrombin-generation test (TGT) and epitope mapping. Two patients were treated during ITI, first with a recombinant FVIII and then with plasma-derived factor VIII without success, and, finally, with Octanate. Bypassing agents were used based on the results of TGT. Epitope mapping was performed during ITI therapy. These observations suggest the potential contribution of Octanate in the management of ITI in difficult cases. The use of bypassing agents can be necessary in prophylaxis or to treat bleedings, and may be guided by TGT results. Epitope mapping is used to describe the inhibitor. This article shows a decrease of the inhibitor directed against the C2 domain after initiation of Octanate. A high-purity human factor VIII/von Willebrand factor concentrate (Octanate) may be a valuable therapeutical option for ITI therapy. TGT and epitope mapping could be of help in the management of ITI. PMID:26517064

  18. The effectiveness of power-generating complexes constructed on the basis of nuclear power plants combined with additional sources of energy determined taking risk factors into account

    NASA Astrophysics Data System (ADS)

    Aminov, R. Z.; Khrustalev, V. A.; Portyankin, A. V.

    2015-02-01

    The effectiveness of combining nuclear power plants equipped with water-cooled water-moderated power-generating reactors (VVER) with other sources of energy within unified power-generating complexes is analyzed. The use of such power-generating complexes makes it possible to achieve the necessary load pickup capability and flexibility in performing the mandatory selective primary and emergency control of load, as well as participation in passing the night minimums of electric load curves while retaining high values of the capacity utilization factor of the entire power-generating complex at higher levels of the steam-turbine part efficiency. Versions involving combined use of nuclear power plants with hydrogen toppings and gas turbine units for generating electricity are considered. In view of the fact that hydrogen is an unsafe energy carrier, the use of which introduces additional elements of risk, a procedure for evaluating these risks under different conditions of implementing the fuel-and-hydrogen cycle at nuclear power plants is proposed. Risk accounting technique with the use of statistical data is considered, including the characteristics of hydrogen and gas pipelines, and the process pipelines equipment tightness loss occurrence rate. The expected intensities of fires and explosions at nuclear power plants fitted with hydrogen toppings and gas turbine units are calculated. In estimating the damage inflicted by events (fires and explosions) occurred in nuclear power plant turbine buildings, the US statistical data were used. Conservative scenarios of fires and explosions of hydrogen-air mixtures in nuclear power plant turbine buildings are presented. Results from calculations of the introduced annual risk to the attained net annual profit ratio in commensurable versions are given. This ratio can be used in selecting projects characterized by the most technically attainable and socially acceptable safety.

  19. Kruppel-like factor KLF4 facilitates cutaneous wound healing by promoting fibrocyte generation from myeloid-derived suppressor cells.

    PubMed

    Ou, Lingling; Shi, Ying; Dong, Wenqi; Liu, Chunming; Schmidt, Thomas J; Nagarkatti, Prakash; Nagarkatti, Mitzi; Fan, Daping; Ai, Walden

    2015-05-01

    Pressure ulcers (PUs) are serious skin injuries whereby the wound healing process is frequently stalled in the inflammatory phase. Myeloid-derived suppressor cells (MDSCs) accumulate as a result of inflammation and promote cutaneous wound healing by mechanisms that are not fully understood. Recently, MDSCs have been shown to differentiate into fibrocytes, which serve as emerging effector cells that enhance cell proliferation in wound healing. We postulate that in wound healing MDSCs not only execute their immunosuppressive function to regulate inflammation but also stimulate cell proliferation once they differentiate into fibrocytes. In the current study, by using full-thickness and PU mouse models, we found that Kruppel-like factor 4 (KLF4) deficiency resulted in decreased accumulation of MDSCs and fibrocytes, and wound healing was significantly delayed. Conversely, KLF4 activation by the plant-derived product Mexicanin I increased the number of MDSCs and fibrocytes and accelerated the wound healing. Collectively, our study revealed a previously unreported function of MDSCs in cutaneous wound healing and identified Mexicanin I as a potential agent to accelerate PU wound healing.

  20. Genetic diversity in HIV-1 subtype C LTR from Brazil and Mozambique generates new transcription factor-binding sites.

    PubMed

    Boullosa, José; Bachu, Mahesh; Bila, Dulce; Ranga, Udaykumar; Süffert, Theodoro; Sasazawa, Tomoko; Tanuri, Amilcar

    2014-06-23

    The HIV-1 subtype C has been substituting the subtype B population in southern Brazil. This phenomenon has been previously described in other countries, suggesting that subtype C may possess greater fitness than other subtypes. The HIV-1 long-terminal repeat (LTR) is an important regulatory region critical for the viral life cycle. Sequence insertions immediately upstream of the viral enhancer are known as the most frequent naturally occurring length polimorphisms (MFNLP). Previous reports demonstrated that the MFNLP could lead to the duplication of transcription factor binding sites (TFBS) enhancing the activity of the HIV-1 subtype C LTR. Here, we amplified and sequenced the LTR obtained from proviral DNA samples collected from patients infected with subtype C from the Southern Region of Brazil (naïve or treatment failure) and Mozambique (only naïve). We confirm the presence of different types of insertions in the LTR sequences of both the countries leading to the creation of additional TFBS. In the Brazilian clinical samples, the frequency of the sequence insertion was significantly higher in subjects experiencing treatment failure than in antiretroviral naïve patients.

  1. Plumbagin Promotes the Generation of Astrocytes from Rat Spinal Cord Neural Progenitors Via Activation of the Transcription Factor Stat3

    PubMed Central

    Luo, Yongquan; Mughal, Mohamed; Ouyang, Xin; Jiang, Haiyang; Luo, Tae-Gen Son Weiming; Yu, Qian-Sheng; Greig, Nigel H.; Mattson, Mark P.

    2010-01-01

    Plumbagin (5-hydroxy-2-methyl-1,4 naphthoquinone) is a naturally occurring low molecular weight lipophilic phytochemical derived from roots of plants of the Plumbago genus. Plumbagin has been reported to have several clinically relevant biological activities in non-neural cells including antiatherosclerotic, anticoagulant, anticarcinogenic, antitumor and bactericidal effects. In a recent screen of a panel of botanical pesticides we identified plumbagin as having neuroprotective activity. In the present study we determined if plumbagin could modify the developmental fate of rat E14.5 embryonic neural progenitor cells (NPC). Plumbagin exhibited no cytotoxicity when applied to cultured NPC at concentrations below 1 µM. At a concentration of 0.1 µM, plumbagin significantly enhanced the proliferation of NPC as indicated by a 17% increase in the percentage of cells incorporating bromo-deoxyuridine. plumbagin at a concentration of 0.1 pM (but not 0.1 µM), stimulated the production of astrocytes as indicated by increased GFAP expression. Plumbagin selectively induced the proliferation and differentiation of glial progenitor cells without affecting the proliferation or differentiation of neuron-restricted progenitors. Plumbagin (0.1 pM) rapidly activated the transcription factor Stat3 in NPC, and a Stat3 inhibitor peptide prevented both plumbagin-induced astrocyte formation and proliferation. These findings demonstrate the ability of a low molecular weight naturally occurring phytochemical to control the fate of glial progenitor cells by a mechanism involving the Stat3 signaling pathway. PMID:20456019

  2. Sanguinarine Inhibits Vascular Endothelial Growth Factor Release by Generation of Reactive Oxygen Species in MCF-7 Human Mammary Adenocarcinoma Cells

    PubMed Central

    Dong, Xian-zhe; Zhang, Miao; Wang, Kun; Liu, Ping; Guo, Dai-hong; Zheng, Xiao-li; Ge, Xiao-yue

    2013-01-01

    The inhibitory action and the possible mechanism of anticancer compound Sanguinarine (SAN) on vascular endothelial growth factor (VEGF) in human mammary adenocarcinoma cells MCF-7 were evaluated in this study. We exposed MCF-7 to SAN for 24 h, then cell viability was assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Human VEGF was measured using a paired antibody quantitative ELISA kit, relative expression of VEGF mRNA was calculated using the real-time PCR studies, and the effect of SAN on the reactive oxygen species (ROS) level was detected by the flow cytometer. Treatment with SAN remarkably inhibited growth of MCF-7 cells and induced cell apoptosis. We found that VEGF release was stimulated by subtoxic concentrations of SAN and inhibited by high dose of SAN, SAN-evoked VEGF release was mimicked by low concentration of H2O2, and SAN-regulated VEGF inhibition was accompanied by increasing of ROS; these changes were abolished by antioxidant. High concentration of SAN inhibited VEGF mRNA expression in MCF-7 cultures, suggesting an effect at transcriptional level, and was also abolished by antioxidant. The present findings indicated that the regulation of VEGF expression and release from MCF-7 cells were possibly through reactive oxygen species evoked by SAN. PMID:23762849

  3. Major controlling factors on hydrocarbon generation and leakage in South Atlantic conjugate margins: A comparative study of Colorado, Orange, Campos and Lower Congo basins

    NASA Astrophysics Data System (ADS)

    Marcano, Gabriela; Anka, Zahie; di Primio, Rolando

    2013-09-01

    We present a supra-regional comparative study of the major internal and external factors controlling source rock (SR) maturation and hydrocarbon (HC) generation and leakage in two pairs of conjugate margins across the South Atlantic: the Brazil (Campos Basin)-Angola (Lower Congo Basin) margins located in the "central segment", and the Argentina (Colorado Basin)-South Africa (Orange Basin) in the "southern segment". Our approach is based on the analysis and integration of borehole data, 1D numerical modeling, 2D seismic reflection data, and published reports. Coupling of modeling results, sedimentation rate calculation and seal-bypass system analysis reveal that: (1) oil window is reached by syn-rift SRs in the southern segment during the Early to Late Cretaceous when thermal subsidence is still active, while in the central segment they reach it in Late-Cretaceous-Neogene during a salt remobilization phase, and (2) early HC generation from post-rift SRs in the southern segment and from all SRs in the central segment appears to be controlled mainly by episodes of increased sedimentation rates. The latter seems to be associated with the Andes uplift history for the western South Atlantic basins (Campos and Colorado) and to a possibly climate-driven response for the eastern South Atlantic basins (Orange and Lower Congo). Additionally, we observe that the effect of volcanism on SR maturation in the southern segment is very local. The comparison of Cretaceous mass transport deposit (MTD) episodes with HC peak of generation and paleo-leakage indicators in the southern segment revealed the possible causal effect that HC generation and leakage have over MTD development. Interestingly, Paleogene leakage indicators, which were identified in the Argentina-South Africa conjugate margins, occur contemporaneously to low sedimentation rate periods. Nonetheless, present-day leakage indicators which were also identified in both pairs of conjugate margins might be related to seal

  4. Diagnostic throughput factor analysis for en-route airspace and optimal aircraft trajectory generation based on capacity prediction and controller workload

    NASA Astrophysics Data System (ADS)

    Shin, Sanghyun

    Today's National Airspace System (NAS) is approaching its limit to efficiently cope with the increasing air traffic demand. Next Generation Air Transportation System (NextGen) with its ambitious goals aims to make the air travel more predictable with fewer delays, less time sitting on the ground and holding in the air to improve the performance of the NAS. However, currently the performance of the NAS is mostly measured using delay-based metrics which do not capture a whole range of important factors that determine the quality and level of utilization of the NAS. The factors affecting the performance of the NAS are themselves not well defined to begin with. To address these issues, motivated by the use of throughput-based metrics in many areas such as ground transportation, wireless communication and manufacturing, this thesis identifies the different factors which majorly affect the performance of the NAS as demand (split into flight cancellation and flight rerouting), safe separation (split into conflict and metering) and weather (studied as convective weather) through careful comparison with other applications and performing empirical sensitivity analysis. Additionally, the effects of different factors on the NAS's performance are quantitatively studied using real traffic data with the Future ATM Concepts Evaluation Tool (FACET) for various sectors and centers of the NAS on different days. In this thesis we propose a diagnostic tool which can analyze the factors that have greater responsibility for regions of poor and better performances of the NAS. Based on the throughput factor analysis for en-route airspace, it was found that weather and controller workload are the major factors that decrease the efficiency of the airspace. Also, since resources such as air traffic controllers, infrastructure and airspace are limited, it is becoming increasingly important to use the available resources efficiently. To alleviate the impact of the weather and controller

  5. Mitigating environmental impacts through the energetic use of wood: Regional displacement factors generated by means of substituting non-wood heating systems.

    PubMed

    Wolf, Christian; Klein, Daniel; Richter, Klaus; Weber-Blaschke, Gabriele

    2016-11-01

    Wood biomass, especially when applied for heating, plays an important role for mitigating environmental impacts such as climate change and the transition towards higher shares of renewable energy in today's energy mix. However, the magnitude of mitigation benefits and burdens associated with wood use can vary greatly depending on regional parameters such as the displaced fossil reference or heating mix. Therefore, regionalized displacement factors, considering region-specific production conditions and substituted products are required when assessing the precise contribution of wood biomass towards the mitigation of environmental impacts. We carried out Life Cycle Assessments of wood heating systems for typical Bavarian conditions and substitute energy carriers with a focus on climate change and particulate matter emissions. In order to showcase regional effects, we created weighted displacement factors for the region of Bavaria, based on installed capacities of individual wood heating systems and the harvested tree species distribution. The study reveals that GHG displacements between -57gCO2-eq.∗MJ(-1) of useful energy through the substitution of natural gas with a 15kW spruce pellets heating system and -165gCO2-eq.∗MJ(-1) through the substitution of power utilized for heating with a modern 6kW beech split log heating system can be achieved. It was shown that the GHG mitigation potentials of wood utilization are overestimated through the common use of light fuel oil as the only reference system. We further propose a methodology for the calculation of displacement factors which is adaptable to other regions worldwide. Based on our approach it is possible to generate displacement factors for wood heating systems which enable accurate decision-making for project planning in households, heating plants, communities and also for entire regions. PMID:27348704

  6. Mitigating environmental impacts through the energetic use of wood: Regional displacement factors generated by means of substituting non-wood heating systems.

    PubMed

    Wolf, Christian; Klein, Daniel; Richter, Klaus; Weber-Blaschke, Gabriele

    2016-11-01

    Wood biomass, especially when applied for heating, plays an important role for mitigating environmental impacts such as climate change and the transition towards higher shares of renewable energy in today's energy mix. However, the magnitude of mitigation benefits and burdens associated with wood use can vary greatly depending on regional parameters such as the displaced fossil reference or heating mix. Therefore, regionalized displacement factors, considering region-specific production conditions and substituted products are required when assessing the precise contribution of wood biomass towards the mitigation of environmental impacts. We carried out Life Cycle Assessments of wood heating systems for typical Bavarian conditions and substitute energy carriers with a focus on climate change and particulate matter emissions. In order to showcase regional effects, we created weighted displacement factors for the region of Bavaria, based on installed capacities of individual wood heating systems and the harvested tree species distribution. The study reveals that GHG displacements between -57gCO2-eq.∗MJ(-1) of useful energy through the substitution of natural gas with a 15kW spruce pellets heating system and -165gCO2-eq.∗MJ(-1) through the substitution of power utilized for heating with a modern 6kW beech split log heating system can be achieved. It was shown that the GHG mitigation potentials of wood utilization are overestimated through the common use of light fuel oil as the only reference system. We further propose a methodology for the calculation of displacement factors which is adaptable to other regions worldwide. Based on our approach it is possible to generate displacement factors for wood heating systems which enable accurate decision-making for project planning in households, heating plants, communities and also for entire regions.

  7. Science versus the stars: a double-blind test of the validity of the NEO Five-Factor Inventory and computer-generated astrological natal charts.

    PubMed

    Wyman, Alyssa Jayne; Vyse, Stuart

    2008-07-01

    The authors asked 52 college students (38 women, 14 men, M age = 19.3 years, SD = 1.3 years) to identify their personality summaries by using a computer-generated astrological natal chart when presented with 1 true summary and 1 bogus one. Similarly, the authors asked participants to identify their true personality profile from real and bogus summaries that the authors derived from the NEO Five-Factor Inventory (NEO-FFI; P. T. Costa Jr. & R. R. McCrae, 1985). Participants identified their real NEO-FFI profiles at a greater-than-chance level but were unable to identify their real astrological summaries. The authors observed a P. T. Barnum effect in the accuracy ratings of both psychological and astrological measures but did not find differences between the odd-numbered (i.e., favorable) signs and the even-numbered (i.e., unfavorable) signs.

  8. Overcoming resistance to first/second generation epidermal growth factor receptor tyrosine kinase inhibitors and ALK inhibitors in oncogene-addicted advanced non-small cell lung cancer

    PubMed Central

    Romanidou, Ourania; Landi, Lorenza; Cappuzzo, Federico; Califano, Raffaele

    2016-01-01

    Epidermal growth factor receptor (EGFR) activating mutations and anaplastic lymphoma kinase (ALK) gene rearrangement in advanced non-small cell lung cancer (NSCLC) represent the two oncogenic events with an impact on current clinical practice. EGFR tyrosine kinase inhibitors (TKIs) and crizotinib are the standard of care for the treatment of EGFR mutant and ALK gene rearranged advanced NSCLC patients. Unfortunately, despite initial clinical benefit, acquired resistance to EGFR-TKIs or crizotinib usually develops after an average of 10–12 months of treatment. The aim of this review is to describe the mechanisms of resistance to first/second generation EGFR-TKIs and crizotinib. In particular, we focus on strategies to overcome resistance due to secondary EGFR T790M mutation and mutations of the ALK domain. PMID:27239236

  9. Science versus the stars: a double-blind test of the validity of the NEO Five-Factor Inventory and computer-generated astrological natal charts.

    PubMed

    Wyman, Alyssa Jayne; Vyse, Stuart

    2008-07-01

    The authors asked 52 college students (38 women, 14 men, M age = 19.3 years, SD = 1.3 years) to identify their personality summaries by using a computer-generated astrological natal chart when presented with 1 true summary and 1 bogus one. Similarly, the authors asked participants to identify their true personality profile from real and bogus summaries that the authors derived from the NEO Five-Factor Inventory (NEO-FFI; P. T. Costa Jr. & R. R. McCrae, 1985). Participants identified their real NEO-FFI profiles at a greater-than-chance level but were unable to identify their real astrological summaries. The authors observed a P. T. Barnum effect in the accuracy ratings of both psychological and astrological measures but did not find differences between the odd-numbered (i.e., favorable) signs and the even-numbered (i.e., unfavorable) signs. PMID:18649494

  10. Generation of functional insulin-producing cells from mouse embryonic stem cells through 804G cell-derived extracellular matrix and protein transduction of transcription factors.

    PubMed

    Kaitsuka, Taku; Noguchi, Hirofumi; Shiraki, Nobuaki; Kubo, Takuya; Wei, Fan-Yan; Hakim, Farzana; Kume, Shoen; Tomizawa, Kazuhito

    2014-01-01

    Embryonic stem (ES) and induced pluripotent stem (iPS) cells have potential applications to regenerative medicine for diabetes; however, a useful and safe way to generate pancreatic β cells has not been developed. In this study, we tried to establish an effective method of differentiation through the protein transduction of three transcription factors (Pdx1, NeuroD, and MafA) important to pancreatic β cell development. The method poses no risk of unexpected genetic modifications in target cells. Transduction of the three proteins induced the differentiation of mouse ES and mouse iPS cells into insulin-producing cells. Furthermore, a laminin-5-rich extracellular matrix efficiently induced differentiation under feeder-free conditions. Cell differentiation was confirmed with the expression of the insulin 1 gene in addition to marker genes in pancreatic β cells, the differentiated cells secreted glucose-responsive C-peptide, and their transplantation restored normoglycemia in diabetic mice. Moreover, Pdx1 protein transduction had facilitative effects on differentiation into pancreatic endocrine progenitors from human iPS cells. These results suggest the direct delivery of recombinant proteins and treatment with laminin-5-rich extracellular matrix to be useful for the generation of insulin-producing cells.

  11. GTP activator and dNTP substrates of HIV-1 restriction factor SAMHD1 generate a long-lived activated state

    PubMed Central

    Hansen, Erik C.; Seamon, Kyle J.; Cravens, Shannen L.; Stivers, James T.

    2014-01-01

    The HIV-1 restriction factor sterile α-motif/histidine-aspartate domain-containing protein 1 (SAMHD1) is a tetrameric protein that catalyzes the hydrolysis of all dNTPs to the deoxynucleoside and tripolyphosphate, which effectively depletes the dNTP substrates of HIV reverse transcriptase. Here, we establish that SAMHD1 is activated by GTP binding to guanine-specific activator sites (A1) as well as coactivation by substrate dNTP binding to a distinct set of nonspecific activator sites (A2). Combined activation by GTP and dNTPs results in a long-lived tetrameric form of SAMHD1 that persists for hours, even after activating nucleotides are withdrawn from the solution. These results reveal an ordered model for assembly of SAMHD1 tetramer from its inactive monomer and dimer forms, where GTP binding to the A1 sites generates dimer and dNTP binding to the A2 and catalytic sites generates active tetramer. Thus, cellular regulation of active SAMHD1 is not determined by GTP alone but instead, the levels of all dNTPs and the generation of a persistent tetramer that is not in equilibrium with free activators. The significance of the long-lived activated state is that SAMHD1 can remain active long after dNTP pools have been reduced to a level that would lead to inactivation. This property would be important in resting CD4+ T cells, where dNTP pools are reduced to nanomolar levels to restrict infection by HIV-1. PMID:24753578

  12. Efficient large-scale generation of functional hepatocytes from mouse embryonic stem cells grown in a rotating bioreactor with exogenous growth factors and hormones

    PubMed Central

    2013-01-01

    Introduction Embryonic stem (ES) cells are considered a potentially advantageous source of hepatocytes for both transplantation and the development of bioartificial livers. However, the efficient large-scale generation of functional hepatocytes from ES cells remains a major challenge, especially for those methods compatible with clinical applications. Methods In this study, we investigated whether a large number of functional hepatocytes can be differentiated from mouse ES (mES) cells using a simulated microgravity bioreactor. mES cells were cultured in a rotating bioreactor in the presence of exogenous growth factors and hormones to form embryoid bodies (EBs), which then differentiated into hepatocytes. Results During the rotating culture, most of the EB-derived cells gradually showed the histologic characteristics of normal hepatocytes. More specifically, the expression of hepatic genes and proteins was detected at a higher level in the differentiated cells from the bioreactor culture than in cells from a static culture. On further growing, the EBs on tissue-culture plates, most of the EB-derived cells were found to display the morphologic features of hepatocytes, as well as albumin synthesis. In addition, the EB-derived cells grown in the rotating bioreactor exhibited higher levels of liver-specific functions, such as glycogen storage, cytochrome P450 activity, low-density lipoprotein, and indocyanine green uptake, than did differentiated cells grown in static culture. When the EB-derived cells from day-14 EBs and the cells’ culture supernatant were injected into nude mice, the transplanted cells were engrafted into the recipient livers. Conclusions Large quantities of high-quality hepatocytes can be generated from mES cells in a rotating bioreactor via EB formation. This system may be useful in the large-scale generation of hepatocytes for both cell transplantation and the development of bioartificial livers. PMID:24294908

  13. Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition

    PubMed Central

    Rothdiener, Miriam; Hegemann, Miriam; Uynuk-Ool, Tatiana; Walters, Brandan; Papugy, Piruntha; Nguyen, Phong; Claus, Valentin; Seeger, Tanja; Stoeckle, Ulrich; Boehme, Karen A.; Aicher, Wilhelm K.; Stegemann, Jan P.; Hart, Melanie L.; Kurz, Bodo; Klein, Gerd; Rolauffs, Bernd

    2016-01-01

    Using matrix elasticity and cyclic stretch have been investigated for inducing mesenchymal stromal cell (MSC) differentiation towards the smooth muscle cell (SMC) lineage but not in combination. We hypothesized that combining lineage-specific stiffness with cyclic stretch would result in a significantly increased expression of SMC markers, compared to non-stretched controls. First, we generated dense collagen type I sheets by mechanically compressing collagen hydrogels. Atomic force microscopy revealed a nanoscale stiffness range known to support myogenic differentiation. Further characterization revealed viscoelasticity and stable biomechanical properties under cyclic stretch with >99% viable adherent human MSC. MSCs on collagen sheets demonstrated a significantly increased mRNA but not protein expression of SMC markers, compared to on culture flasks. However, cyclic stretch of MSCs on collagen sheets significantly increased both mRNA and protein expression of α-smooth muscle actin, transgelin, and calponin versus plastic and non-stretched sheets. Thus, lineage-specific stiffness and cyclic stretch can be applied together for inducing MSC differentiation towards SMCs without the addition of recombinant growth factors or other soluble factors. This represents a novel stimulation method for modulating the phenotype of MSCs towards SMCs that could easily be incorporated into currently available methodologies to obtain a more targeted control of MSC phenotype. PMID:27775041

  14. Interleukin 1 beta suppresses transforming growth factor-induced inorganic pyrophosphate (PPi) production and expression of the PPi-generating enzyme PC-1 in human chondrocytes.

    PubMed Central

    Lotz, M; Rosen, F; McCabe, G; Quach, J; Blanco, F; Dudler, J; Solan, J; Goding, J; Seegmiller, J E; Terkeltaub, R

    1995-01-01

    Articular cartilage chondrocytes have the unique ability to elaborate large amounts of extracellular pyrophosphate (PPi), and transforming growth factor beta (TGF beta) appears singular among cartilage regulatory factors in stimulating PPi production. TGF beta caused a time and dose-dependent increase in intracellular and extracellular PPi in human articular chondrocyte cultures. TGF beta and interleukin 1 beta (IL-1 beta) antagonistically regulate certain chondrocyte functions. IL-1 beta profoundly inhibited basal and TGF beta-induced PPi elaboration. To address mechanisms involved with the regulation of PPi synthesis by IL-1 beta and TGF beta, we analyzed the activity of the PPi-generating enzyme NTP pyrophosphohydrolase (NTPPPH) and the PPi-hydrolyzing enzyme alkaline phosphatase. Human chondrocyte NTPPPH activity was largely attributable to plasma cell membrane glycoprotein 1, PC-1. Furthermore, TGF beta induced comparable increases in the activity of extracellular PPi, intracellular PPi, and cellular NTPPPH and in the levels of PC-1 protein and mRNA in chondrocytes as well as a decrease in alkaline phosphatase. All of these TGF beta-induced responses were completely blocked by IL-1 beta. Thus, IL-1 beta may be an important regulator of mineralization in chondrocytes by inhibiting TGF beta-induced PPi production and PC-1 expression. Images Fig. 4 Fig. 5 PMID:7479785

  15. A Hox Transcription Factor Collective Binds a Highly Conserved Distal-less cis-Regulatory Module to Generate Robust Transcriptional Outcomes

    PubMed Central

    Uhl, Juli D.; Zandvakili, Arya; Gebelein, Brian

    2016-01-01

    cis-regulatory modules (CRMs) generate precise expression patterns by integrating numerous transcription factors (TFs). Surprisingly, CRMs that control essential gene patterns can differ greatly in conservation, suggesting distinct constraints on TF binding sites. Here, we show that a highly conserved Distal-less regulatory element (DCRE) that controls gene expression in leg precursor cells recruits multiple Hox, Extradenticle (Exd) and Homothorax (Hth) complexes to mediate dual outputs: thoracic activation and abdominal repression. Using reporter assays, we found that abdominal repression is particularly robust, as neither individual binding site mutations nor a DNA binding deficient Hth protein abolished cooperative DNA binding and in vivo repression. Moreover, a re-engineered DCRE containing a distinct configuration of Hox, Exd, and Hth sites also mediated abdominal Hox repression. However, the re-engineered DCRE failed to perform additional segment-specific functions such as thoracic activation. These findings are consistent with two emerging concepts in gene regulation: First, the abdominal Hox/Exd/Hth factors utilize protein-protein and protein-DNA interactions to form repression complexes on flexible combinations of sites, consistent with the TF collective model of CRM organization. Second, the conserved DCRE mediates multiple cell-type specific outputs, consistent with recent findings that pleiotropic CRMs are associated with conserved TF binding and added evolutionary constraints. PMID:27058369

  16. A Hox Transcription Factor Collective Binds a Highly Conserved Distal-less cis-Regulatory Module to Generate Robust Transcriptional Outcomes.

    PubMed

    Uhl, Juli D; Zandvakili, Arya; Gebelein, Brian

    2016-04-01

    cis-regulatory modules (CRMs) generate precise expression patterns by integrating numerous transcription factors (TFs). Surprisingly, CRMs that control essential gene patterns can differ greatly in conservation, suggesting distinct constraints on TF binding sites. Here, we show that a highly conserved Distal-less regulatory element (DCRE) that controls gene expression in leg precursor cells recruits multiple Hox, Extradenticle (Exd) and Homothorax (Hth) complexes to mediate dual outputs: thoracic activation and abdominal repression. Using reporter assays, we found that abdominal repression is particularly robust, as neither individual binding site mutations nor a DNA binding deficient Hth protein abolished cooperative DNA binding and in vivo repression. Moreover, a re-engineered DCRE containing a distinct configuration of Hox, Exd, and Hth sites also mediated abdominal Hox repression. However, the re-engineered DCRE failed to perform additional segment-specific functions such as thoracic activation. These findings are consistent with two emerging concepts in gene regulation: First, the abdominal Hox/Exd/Hth factors utilize protein-protein and protein-DNA interactions to form repression complexes on flexible combinations of sites, consistent with the TF collective model of CRM organization. Second, the conserved DCRE mediates multiple cell-type specific outputs, consistent with recent findings that pleiotropic CRMs are associated with conserved TF binding and added evolutionary constraints. PMID:27058369

  17. A Hox Transcription Factor Collective Binds a Highly Conserved Distal-less cis-Regulatory Module to Generate Robust Transcriptional Outcomes.

    PubMed

    Uhl, Juli D; Zandvakili, Arya; Gebelein, Brian

    2016-04-01

    cis-regulatory modules (CRMs) generate precise expression patterns by integrating numerous transcription factors (TFs). Surprisingly, CRMs that control essential gene patterns can differ greatly in conservation, suggesting distinct constraints on TF binding sites. Here, we show that a highly conserved Distal-less regulatory element (DCRE) that controls gene expression in leg precursor cells recruits multiple Hox, Extradenticle (Exd) and Homothorax (Hth) complexes to mediate dual outputs: thoracic activation and abdominal repression. Using reporter assays, we found that abdominal repression is particularly robust, as neither individual binding site mutations nor a DNA binding deficient Hth protein abolished cooperative DNA binding and in vivo repression. Moreover, a re-engineered DCRE containing a distinct configuration of Hox, Exd, and Hth sites also mediated abdominal Hox repression. However, the re-engineered DCRE failed to perform additional segment-specific functions such as thoracic activation. These findings are consistent with two emerging concepts in gene regulation: First, the abdominal Hox/Exd/Hth factors utilize protein-protein and protein-DNA interactions to form repression complexes on flexible combinations of sites, consistent with the TF collective model of CRM organization. Second, the conserved DCRE mediates multiple cell-type specific outputs, consistent with recent findings that pleiotropic CRMs are associated with conserved TF binding and added evolutionary constraints.

  18. Generation of Mice Deficient in both KLF3/BKLF and KLF8 Reveals a Genetic Interaction and a Role for These Factors in Embryonic Globin Gene Silencing

    PubMed Central

    Funnell, Alister P. W.; Mak, Ka Sin; Twine, Natalie A.; Pelka, Gregory J.; Norton, Laura J.; Radziewic, Tania; Power, Melinda; Wilkins, Marc R.; Bell-Anderson, Kim S.; Fraser, Stuart T.; Perkins, Andrew C.; Tam, Patrick P.; Pearson, Richard C. M.

    2013-01-01

    Krüppel-like factors 3 and 8 (KLF3 and KLF8) are highly related transcriptional regulators that bind to similar sequences of DNA. We have previously shown that in erythroid cells there is a regulatory hierarchy within the KLF family, whereby KLF1 drives the expression of both the Klf3 and Klf8 genes and KLF3 in turn represses Klf8 expression. While the erythroid roles of KLF1 and KLF3 have been explored, the contribution of KLF8 to this regulatory network has been unknown. To investigate this, we have generated a mouse model with disrupted KLF8 expression. While these mice are viable, albeit with a reduced life span, mice lacking both KLF3 and KLF8 die at around embryonic day 14.5 (E14.5), indicative of a genetic interaction between these two factors. In the fetal liver, Klf3 Klf8 double mutant embryos exhibit greater dysregulation of gene expression than either of the two single mutants. In particular, we observe derepression of embryonic, but not adult, globin expression. Taken together, these results suggest that KLF3 and KLF8 have overlapping roles in vivo and participate in the silencing of embryonic globin expression during development. PMID:23716600

  19. Generation of Naïve Bovine Induced Pluripotent Stem Cells Using PiggyBac Transposition of Doxycycline-Inducible Transcription Factors.

    PubMed

    Kawaguchi, Takamasa; Tsukiyama, Tomoyuki; Kimura, Koji; Matsuyama, Shuichi; Minami, Naojiro; Yamada, Masayasu; Imai, Hiroshi

    2015-01-01

    Generation of pluripotent stem cells (PSCs) in large domestic animals has achieved only limited success; most of the PSCs obtained to date have been classified as primed PSCs, which possess very little capacity to produce chimeric offspring. By contrast, mouse PSCs have been classified as naïve PSCs that can contribute to most of the tissues of chimeras, including germ cells. Here, we describe the generation of two different types of bovine induced pluripotent stem cells (biPSCs) from amnion cells, achieved through introduction of piggyBac vectors containing doxycycline-inducible transcription factors (Oct3/4, Sox2, Klf4, and c-Myc). One type of biPSCs, cultured in medium supplemented with knockout serum replacement (KSR), FGF2, and bovine leukemia inhibitory factor (bLIF), had a flattened morphology like human PSCs; these were classified as primed-type. The other type biPSCs, cultured in KSR, bLIF, Mek/Erk inhibitor, GSK3 inhibitor and forskolin, had a compact morphology like mouse PSCs; these were classified as naïve-type. Cells could easily be switched between these two types of biPSCs by changing the culture conditions. Both types of biPSCs had strong alkaline phosphatase activity, expressed pluripotent markers (OCT3/4, NANOG, REX1, ESRRβ, STELLA, and SOCS3), and formed embryoid bodies that gave rise to differentiated cells from all three embryonic germ layers. However, only naïve-type biPSCs showed the hallmarks of naïve mouse PSCs, such as LIF-dependent proliferation, lack of FGF5 expression, and active XIST expression with two active X chromosomes. Furthermore, naïve-type biPSCs could contribute to the inner cell mass (ICM) of host blastocysts and most tissues within chimeric embryos. This is the first report of generation of biPSCs with several characteristics similar to those of naïve mouse PSCs and a demonstrated potential to contribute to chimeras. PMID:26287611

  20. Activation of nuclear factor erythroid 2-related factor 2 coordinates dimethylarginine dimethylaminohydrolase/PPAR-γ/endothelial nitric oxide synthase pathways that enhance nitric oxide generation in human glomerular endothelial cells.

    PubMed

    Luo, Zaiming; Aslam, Shakil; Welch, William J; Wilcox, Christopher S

    2015-04-01

    Dimethylarginine dimethylaminohydrolase (DDAH) degrades asymmetric dimethylarginine, which inhibits nitric oxide (NO) synthase (NOS). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that binds to antioxidant response elements and transcribes many antioxidant genes. Because the promoters of the human DDAH-1 and DDAH-2, endothelial NOS (eNOS) and PPAR-γ genes contain 2 to 3 putative antioxidant response elements, we hypothesized that they were regulated by Nrf2/antioxidant response element. Incubation of human renal glomerular endothelial cells with the Nrf2 activator tert-butylhydroquinone (20 μmol·L(-1)) significantly (P<0.05) increased NO and activities of NOS and DDAH and decreased asymmetric dimethylarginine. It upregulated genes for hemoxygenase-1, eNOS, DDAH-1, DDAH-2, and PPAR-γ and partitioned Nrf2 into the nucleus. Knockdown of Nrf2 abolished these effects. Nrf2 bound to one antioxidant response element on DDAH-1 and DDAH-2 and PPAR-γ promoters but not to the eNOS promoter. An increased eNOS and phosphorylated eNOS (P-eNOSser-1177) expression with tert-butylhydroquinone was prevented by knockdown of PPAR-γ. Expression of Nrf2 was reduced by knockdown of PPAR-γ, whereas PPAR-γ was reduced by knockdown of Nrf2, thereby demonstrating 2-way positive interactions. Thus, Nrf2 transcribes HO-1 and other genes to reduce reactive oxygen species, and DDAH-1 and DDAH-2 to reduce asymmetric dimethylarginine and PPAR-γ to increase eNOS and its phosphorylation and activity thereby coordinating 3 pathways that enhance endothelial NO generation. PMID:25691623

  1. Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial.

    PubMed

    Heigener, David F; Pereira, José Rodrigues; Felip, Enriqueta; Mazal, Juraj; Manzyuk, Lyudmila; Tan, Eng Huat; Merimsky, Ofer; Sarholz, Barbara; Esser, Regina; Gatzemeier, Ulrich

    2015-06-01

    The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly improved survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755) investigated the efficacy and safety of weekly and every 2 weeks cetuximab maintenance therapy in this setting. Patients were treated with platinum-based chemotherapy plus cetuximab, and those progression-free after four to six cycles were randomized to every 2 weeks (500 mg/m(2)) or weekly (250 mg/m(2)) cetuximab maintenance. Randomization was stratified for tumor histology and response status. The primary endpoint for a regimen would be reached if the lower boundary of the 95 % confidence interval (CI) for the 1-year survival rate exceeded 55 %. A planned 480 patients were to be randomized. However, enrollment was curtailed following a negative opinion from the European Medicines Agency with regard to the use of cetuximab in this setting. After combination therapy, 311/583 (53.3 %) patients without progression were randomized to maintenance therapy: 157 to every 2 weeks cetuximab and 154 to weekly cetuximab. Baseline characteristics were balanced between these groups and exposure to cetuximab was similar. The 1-year survival rate was 62.8 % (95 % CI, 54.7-70.0) for every 2 weeks cetuximab and 64.4 % (95 % CI, 56.2-71.4) for weekly cetuximab. Safety profiles were similar, manageable, and in line with expectations. Therefore, in patients with advanced NSCLC who were progression-free after four to six cycles of first-line chemotherapy plus cetuximab, weekly and every 2 weeks cetuximab maintenance therapy were associated with similar survival outcomes.

  2. Nonresected Non-Small-Cell Lung Cancer in Stages I Through IIIB: Accelerated, Twice-Daily, High-Dose Radiotherapy-A Prospective Phase I/II Trial With Long-Term Follow-Up

    SciTech Connect

    Wurstbauer, Karl; Deutschmann, Heinz; Kopp, Peter; Kranzinger, Manfred; Merz, Florian; Nairz, Olaf; Studnicka, Michael; Sedlmayer, Felix

    2010-08-01

    Purpose: Our purpose was to investigate the tolerability of accelerated, twice-daily, high-dose radiotherapy. The secondary endpoints were survival and locoregional tumor control. Methods and Materials: Thirty consecutive patients with histologically/cytologically proven non-small-cell lung cancer were enrolled. Tumor Stage I, II, IIIA, and IIIB was found in 7, 3, 12, and 8 patients, respectively. We applied a median of 84.6 Gy (range, 75.6-90.0 Gy) to the primary tumors, 63.0 Gy (range, 59.4-72.0 Gy) to lymph nodes, and 45 Gy to nodes electively (within a region of about 6 cm cranial to macroscopically involved sites). Fractional doses of 1.8 Gy twice daily, with an interval of 11 hours, were given, resulting in a median treatment time of 35 days. In the majority of patients the conformal target-splitting technique was used. In 19 patients (63%) two cycles of induction chemotherapy were given. The median follow-up time of survivors is 72 months (range, 62-74 months). Results: We found Grade 1, 2 and 3 acute esophageal toxicity in 11 patients (37%), 2 patients (7%), and 2 patients (7%), respectively. Grade 2 acute pneumonitis was seen in 2 patients (7%). No late toxicity greater than Grade 1 was observed. The actual overall survival rates at 2 and 5 years are 63% and 23%, respectively; the median overall survival, 27.7 months. In 9 patients a local failure occurred, 7 of them presenting initially with an atelectasis without availability of 18-fluorodeoxyglucose-positron emission tomography staging at that time. In 4 patients recurrence occurred regionally. Conclusions: This Phase I/II trial with long-term follow-up shows low toxicity with promising results for survival and locoregional tumor control.

  3. KONJAC1 and 2 Are Key Factors for GDP-Mannose Generation and Affect l-Ascorbic Acid and Glucomannan Biosynthesis in Arabidopsis.

    PubMed

    Sawake, Shota; Tajima, Noriaki; Mortimer, Jenny C; Lao, Jeemeng; Ishikawa, Toshiki; Yu, Xiaolan; Yamanashi, Yukiko; Yoshimi, Yoshihisa; Kawai-Yamada, Maki; Dupree, Paul; Tsumuraya, Yoichi; Kotake, Toshihisa

    2015-12-01

    Humans are unable to synthesize l-ascorbic acid (AsA), yet it is required as a cofactor in many critical biochemical reactions. The majority of human dietary AsA is obtained from plants. In Arabidopsis thaliana, a GDP-mannose pyrophosphorylase (GMPP), VITAMIN C DEFECTIVE1 (VTC1), catalyzes a rate-limiting step in AsA synthesis: the formation of GDP-Man. In this study, we identified two nucleotide sugar pyrophosphorylase-like proteins, KONJAC1 (KJC1) and KJC2, which stimulate the activity of VTC1. The kjc1kjc2 double mutant exhibited severe dwarfism, indicating that KJC proteins are important for growth and development. The kjc1 mutation reduced GMPP activity to 10% of wild-type levels, leading to a 60% reduction in AsA levels. On the contrary, overexpression of KJC1 significantly increased GMPP activity. The kjc1 and kjc1kjc2 mutants also exhibited significantly reduced levels of glucomannan, which is also synthesized from GDP-Man. Recombinant KJC1 and KJC2 enhanced the GMPP activity of recombinant VTC1 in vitro, while KJCs did not show GMPP activity. Yeast two-hybrid assays suggested that the stimulation of GMPP activity occurs via interaction of KJCs with VTC1. These results suggest that KJCs are key factors for the generation of GDP-Man and affect AsA level and glucomannan accumulation through the stimulation of VTC1 GMPP activity.

  4. Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome

    PubMed Central

    Cher, C Y; Leung, G M K; Au, C H; Chan, T L; Ma, E S K; Sim, J P Y; Gill, H; Lie, A K W; Liang, R; Wong, K F; Siu, L L P; Tsui, C S P; So, C C; Wong, H W W; Yip, S F; Lee, H K K; Liu, H S Y; Lau, J S M; Luk, T H; Lau, C K; Lin, S Y; Kwong, Y L; Leung, A Y H

    2016-01-01

    Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18–60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype. PMID:27391574

  5. Pharmacogenomics of insulin-like growth factor-I generation during GH treatment in children with GH deficiency or Turner syndrome

    PubMed Central

    Stevens, A; Clayton, P; Tatò, L; Yoo, H W; Rodriguez-Arnao, M D; Skorodok, J; Ambler, G R; Zignani, M; Zieschang, J; Della Corte, G; Destenaves, B; Champigneulle, A; Raelson, J; Chatelain, P

    2014-01-01

    Individual responses to growth hormone (GH) treatment are variable. Short-term generation of insulin-like growth factor-I (IGF-I) is recognized as a potential marker of sensitivity to GH treatment. This prospective, phase IV study used an integrated genomic analysis to identify markers associated with 1-month change in IGF-I (ΔIGF-I) following initiation of recombinant human (r-h)GH therapy in treatment-naïve children with GH deficiency (GHD) (n=166) or Turner syndrome (TS) (n=147). In both GHD and TS, polymorphisms in the cell-cycle regulator CDK4 were associated with 1-month ΔIGF-I (P<0.05). Baseline gene expression was also correlated with 1-month ΔIGF-I in both GHD and TS (r=0.3; P<0.01). In patients with low IGF-I responses, carriage of specific CDK4 alleles was associated with MAPK and glucocorticoid receptor signaling in GHD, and with p53 and Wnt signaling pathways in TS. Understanding the relationship between genomic markers and early changes in IGF-I may allow development of strategies to rapidly individualize r-hGH dose. PMID:23567489

  6. Effects of production and market factors on ethanol profitability for an integrated first and second generation ethanol plant using the whole sugarcane as feedstock

    PubMed Central

    2014-01-01

    Background Sugarcane is an attractive feedstock for ethanol production, especially if the lignocellulosic fraction can also be treated in second generation (2G) ethanol plants. However, the profitability of 2G ethanol is affected by the processing conditions, operating costs and market prices. This study focuses on the minimum ethanol selling price (MESP) and maximum profitability of ethanol production in an integrated first and second generation (1G + 2G) sugarcane-to-ethanol plant. The feedstock used was sugarcane juice, bagasse and leaves. The lignocellulosic fraction was hydrolysed with enzymes. Yields were assumed to be 95% of the theoretical for each of the critical steps in the process (steam pretreatment, enzymatic hydrolysis (EH), fermentation, solid/liquid separation, anaerobic digestion) in order to obtain the best conditions possible for ethanol production, to assess the lowest production costs. Techno-economic analysis was performed for various combinations of process options (for example use of pentoses, addition of leaves), EH conditions (water-insoluble solids (WIS) and residence time), operating cost (enzymes) and market factors (wholesale prices of electricity and ethanol, cost of the feedstock). Results The greatest reduction in 2G MESP was achieved when using the pentoses for the production of ethanol rather than biogas. This was followed, in decreasing order, by higher enzymatic hydrolysis efficiency (EHE), by increasing the WIS to 30% and by a short residence time (48 hours) in the EH. The addition of leaves was found to have a slightly negative impact on 1G + 2G MESP, but the effect on 2G MESP was negligible. Sugarcane price significantly affected 1G + 2G MESP, while the price of leaves had a much lower impact. Net present value (NPV) analysis of the most interesting case showed that integrated 1G + 2G ethanol production including leaves could be more profitable than 1G ethanol, despite the fact that the MESP was higher than

  7. Longevity of implantable cardioverter-defibrillators for cardiac resynchronization therapy in current clinical practice: an analysis according to influencing factors, device generation, and manufacturer

    PubMed Central

    Landolina, Maurizio; Curnis, Antonio; Morani, Giovanni; Vado, Antonello; Ammendola, Ernesto; D'onofrio, Antonio; Stabile, Giuseppe; Crosato, Martino; Petracci, Barbara; Ceriotti, Carlo; Bontempi, Luca; Morosato, Martina; Ballari, Gian Paolo; Gasparini, Maurizio

    2015-01-01

    Aims Device replacement at the time of battery depletion of implantable cardioverter-defibrillators (ICDs) may carry a considerable risk of complications and engenders costs for healthcare systems. Therefore, ICD device longevity is extremely important both from a clinical and economic standpoint. Cardiac resynchronization therapy defibrillators (CRT-D) battery longevity is shorter than ICDs. We determined the rate of replacements for battery depletion and we identified possible determinants of early depletion in a series of patients who had undergone implantation of CRT-D devices. Methods and results We retrieved data on 1726 consecutive CRT-D systems implanted from January 2008 to March 2010 in nine centres. Five years after a successful CRT-D implantation procedure, 46% of devices were replaced due to battery depletion. The time to device replacement for battery depletion differed considerably among currently available CRT-D systems from different manufacturers, with rates of batteries still in service at 5 years ranging from 52 to 88% (log-rank test, P < 0.001). Left ventricular lead output and unipolar pacing configuration were independent determinants of early depletion [hazard ratio (HR): 1.96; 95% 95% confidence interval (CI): 1.57–2.46; P < 0.001 and HR: 1.58, 95% CI: 1.25–2.01; P < 0.001, respectively]. The implantation of a recent-generation device (HR: 0.57; 95% CI: 0.45–0.72; P < 0.001), the battery chemistry and the CRT-D manufacturer (HR: 0.64; 95% CI: 0.47–0.89; P = 0.008) were additional factors associated with replacement for battery depletion. Conclusion The device longevity at 5 years was 54%. High left ventricular lead output and unipolar pacing configuration were associated with early battery depletion, while recent-generation CRT-Ds displayed better longevity. Significant differences emerged among currently available CRT-D systems from different manufacturers. PMID:25976906

  8. Generation of plasmid vectors expressing FLAG-tagged proteins under the regulation of human elongation factor-1α promoter using Gibson assembly.

    PubMed

    Grozdanov, Petar N; MacDonald, Clinton C

    2015-02-09

    Gibson assembly (GA) cloning offers a rapid, reliable, and flexible alternative to conventional DNA cloning methods. We used GA to create customized plasmids for expression of exogenous genes in mouse embryonic stem cells (mESCs). Expression of exogenous genes under the control of the SV40 or human cytomegalovirus promoters diminishes quickly after transfection into mESCs. A remedy for this diminished expression is to use the human elongation factor-1 alpha (hEF1α) promoter to drive gene expression. Plasmid vectors containing hEF1α are not as widely available as SV40- or CMV-containing plasmids, especially those also containing N-terminal 3xFLAG-tags. The protocol described here is a rapid method to create plasmids expressing FLAG-tagged CstF-64 and CstF-64 mutant under the expressional regulation of the hEF1α promoter. GA uses a blend of DNA exonuclease, DNA polymerase and DNA ligase to make cloning of overlapping ends of DNA fragments possible. Based on the template DNAs we had available, we designed our constructs to be assembled into a single sequence. Our design used four DNA fragments: pcDNA 3.1 vector backbone, hEF1α promoter part 1, hEF1α promoter part 2 (which contained 3xFLAG-tag purchased as a double-stranded synthetic DNA fragment), and either CstF-64 or specific CstF-64 mutant. The sequences of these fragments were uploaded to a primer generation tool to design appropriate PCR primers for generating the DNA fragments. After PCR, DNA fragments were mixed with the vector containing the selective marker and the GA cloning reaction was assembled. Plasmids from individual transformed bacterial colonies were isolated. Initial screen of the plasmids was done by restriction digestion, followed by sequencing. In conclusion, GA allowed us to create customized plasmids for gene expression in 5 days, including construct screens and verification.

  9. Generation of plasmid vectors expressing FLAG-tagged proteins under the regulation of human elongation factor-1α promoter using Gibson assembly.

    PubMed

    Grozdanov, Petar N; MacDonald, Clinton C

    2015-01-01

    Gibson assembly (GA) cloning offers a rapid, reliable, and flexible alternative to conventional DNA cloning methods. We used GA to create customized plasmids for expression of exogenous genes in mouse embryonic stem cells (mESCs). Expression of exogenous genes under the control of the SV40 or human cytomegalovirus promoters diminishes quickly after transfection into mESCs. A remedy for this diminished expression is to use the human elongation factor-1 alpha (hEF1α) promoter to drive gene expression. Plasmid vectors containing hEF1α are not as widely available as SV40- or CMV-containing plasmids, especially those also containing N-terminal 3xFLAG-tags. The protocol described here is a rapid method to create plasmids expressing FLAG-tagged CstF-64 and CstF-64 mutant under the expressional regulation of the hEF1α promoter. GA uses a blend of DNA exonuclease, DNA polymerase and DNA ligase to make cloning of overlapping ends of DNA fragments possible. Based on the template DNAs we had available, we designed our constructs to be assembled into a single sequence. Our design used four DNA fragments: pcDNA 3.1 vector backbone, hEF1α promoter part 1, hEF1α promoter part 2 (which contained 3xFLAG-tag purchased as a double-stranded synthetic DNA fragment), and either CstF-64 or specific CstF-64 mutant. The sequences of these fragments were uploaded to a primer generation tool to design appropriate PCR primers for generating the DNA fragments. After PCR, DNA fragments were mixed with the vector containing the selective marker and the GA cloning reaction was assembled. Plasmids from individual transformed bacterial colonies were isolated. Initial screen of the plasmids was done by restriction digestion, followed by sequencing. In conclusion, GA allowed us to create customized plasmids for gene expression in 5 days, including construct screens and verification. PMID:25742071

  10. Targeted Next-Generation Sequencing of Plasma DNA from Cancer Patients: Factors Influencing Consistency with Tumour DNA and Prospective Investigation of Its Utility for Diagnosis

    PubMed Central

    Kaisaki, Pamela J.; Cutts, Anthony; Popitsch, Niko; Camps, Carme; Pentony, Melissa M.; Wilson, Gareth; Page, Suzanne; Kaur, Kulvinder; Vavoulis, Dimitris; Henderson, Shirley; Gupta, Avinash; Middleton, Mark R.; Karydis, Ioannis; Talbot, Denis C.; Schuh, Anna; Taylor, Jenny C.

    2016-01-01

    Use of circulating tumour DNA (ctDNA) as a liquid biopsy has been proposed for potential identification and monitoring of solid tumours. We investigate a next-generation sequencing approach for mutation detection in ctDNA in two related studies using a targeted panel. The first study was retrospective, using blood samples taken from melanoma patients at diverse timepoints before or after treatment, aiming to evaluate correlation between mutations identified in biopsy and ctDNA, and to acquire a first impression of influencing factors. We found good concordance between ctDNA and tumour mutations of melanoma patients when blood samples were collected within one year of biopsy or before treatment. In contrast, when ctDNA was sequenced after targeted treatment in melanoma, mutations were no longer found in 9 out of 10 patients, suggesting the method might be useful for detecting treatment response. Building on these findings, we focused the second study on ctDNA obtained before biopsy in lung patients, i.e. when a tentative diagnosis of lung cancer had been made, but no treatment had started. The main objective of this prospective study was to evaluate use of ctDNA in diagnosis, investigating the concordance of biopsy and ctDNA-derived mutation detection. Here we also found positive correlation between diagnostic lung biopsy results and pre-biopsy ctDNA sequencing, providing support for using ctDNA as a cost-effective, non-invasive solution when the tumour is inaccessible or when biopsy poses significant risk to the patient. PMID:27626278

  11. Joint health scores in a haemophilia A cohort from Pakistan with minimal or no access to factor VIII concentrate: correlation with thrombin generation and underlying mutation.

    PubMed

    Khanum, F; Bowen, D J; Kerr, B C; Collins, P W

    2014-05-01

    Haemophilia A is associated with recurrent joint bleeding which leads to synovitis and debilitating arthropathy. Coagulation factor VIII level is an important determinant of bleed number and development of arthropathy . The aim of this study was to compare the haemophilia joint health score (HJHS) and Gilbert score with severity, age, thrombin generation (TG) and underlying mutation in a haemophilia A cohort which had minimal access to haemostatic replacement therapy. Ninety-two haemophilia A individuals were recruited from Pakistan. Age, age at first bleed, target joints, haemophilic arthropathy joints, HJHS and Gilbert score were recorded. A strong correlation was found between HJHS and Gilbert score (r = 0.98), both were significantly higher in severe (n = 59) compared with non-severe (n = 29) individuals before the age of 12 years (P ≤ 0.01) but not thereafter. When individuals were divided according to developmental age (<12 years, 12-16 years and >16 years), both HJHS and Gilbert score were significantly lower in the youngest group (P ≤ 0.001), there was no difference between 12-16 years and >16 years. In severe individuals there was no correlation between in vitro TG and joint score, whereas in non-severe individuals there was a weak negative correlation. In the severe group, no significant difference was observed for either joint score according to the underlying mutation type (inversion, missense, nonsense, frameshift). In this cohort of haemophilia A individuals with minimal access to haemostatic treatment, haemophilic arthropathy correlated with severity and age; among severe individuals, joint health scores did not relate to either the underlying mutation or in vitro TG.

  12. Rapid generation of stable cell lines expressing high levels of erythropoietin, factor VIII, and an antihuman CD20 antibody using lentiviral vectors.

    PubMed

    Baranyi, Lajos; Doering, Christopher B; Denning, Gabriella; Gautney, Richard E; Harris, Kyle T; Spencer, H Trent; Roy, Andre; Zayed, Hatem; Dropulic, Boro

    2013-08-01

    Lentiviral vectors (LVs) are widely recognized as the most efficient method for the stable delivery of nucleic acid sequences into mammalian cells. Using erythropoietin (EPO), recombinant factor VIII (fVIII), and an anti-CD20 antibody as model proteins, we demonstrate advantages of LV-based gene delivery to achieve high production levels by transduced cells. Highly productive cell clones were able to incorporate up to 100 vector copies per cellular genome, without selection or gene amplification, and were isolated without extensive screening of a large number of clones. The LV transgenes were shown to be distributed throughout the genome, as visualized by fluorescent in situ hybridization. High-expressing clones producing 100-200 pg/cell/day of EPO were isolated and characterized. EPO production was demonstrated for at least 5½ months of continuous culture without selection, during which all the clones displayed high levels of glycosylation despite production levels at 10-20 g/liter. To demonstrate the utility of LV technology for multiple classes of proteins, cell lines producing fVIII and an anti-CD20 antibody were also developed. Cell clones demonstrating high levels of fVIII (100 clot units/ml and anti-CD20 antibody as high as 40-100 pg/cell/day) were isolated and characterized. LV-transduced cells and plasmid-transfected cells were compared for protein production per transgene copy. LV-transduced cells produced significantly higher levels of protein per copy of transgene than plasmid-transfected cells did. This study demonstrates the utility of LV technology for rapid generation of highly productive and stable cell lines over conventional plasmid transfection methods, significantly decreasing the time, cost, and risk of the manufacture of proteins and other complex biological molecules.

  13. Astrocytes and oligodendrocytes can be generated from NG2+ progenitors after acute brain injury: intracellular localization of oligodendrocyte transcription factor 2 is associated with their fate choice.

    PubMed

    Zhao, Jing-Wei; Raha-Chowdhury, Ruma; Fawcett, James W; Watts, Colin

    2009-05-01

    Brain injury induces gliosis and scar formation; its principal cell types are mainly astrocytes and some oligodendrocytes. The origin of the astrocytes and oligodendrocytes in the scar remains unclear together with the underlying mechanism of their fate choice. We examined the response of oligodendrocyte transcription factor (Olig)2(+) glial progenitors to acute brain injury. Both focal cortical (mechanical or excitotoxic) and systemic (kainic acid-induced seizure or lipopolysaccharide-induced inflammation) injury caused cytoplasmic translocation of Olig2 (Olig2(TL)) exclusively in affected brain regions as early as 2 h after injury in two-thirds of Olig2(+) cells. Many of the proliferating Olig2(+) cells reacting to injury co-expressed chondroitin sulphate proteoglycan neuron/glia antigen 2 (NG2). Using 5-bromodeoxyuridine (BrdU) tracing protocols, proliferating Olig2(TL)GFAP(+)BrdU(+) cells were observed from 2 days post-lesion (dpl). Immature oligodendrocytes were also seen from 2 dpl and all of them retained Olig2 in the nucleus (Olig2(Nuc)). From 5 dpl Olig2(TL)NG2(+)GFAP(+) cells were observed in the wound and some of them were proliferative. From 5 dpl NG2(+)RIP(+) cells were also seen, all of which were Olig2(Nuc) and some of which were also BrdU(+). Our results suggest that, in response to brain injury, NG2(+) progenitors may generate a subpopulation of astrocytes in addition to oligodendrocytes and their fate choice was associated with Olig2(TL) or Olig2(Nuc). However, the NG2(+)GFAP(+) phenotype was only seen within a limited time window (5-8 dpl) when up to 20% of glial fibrillary acidic protein (GFAP) cells co-expressed NG2. We also observed Olig2(TL)GFAP(+) cells that appeared after injury and before the NG2(+)GFAP(+) phenotype. This suggests that not all astrocytes are derived from an NG2(+) population. PMID:19473238

  14. Targeted Next-Generation Sequencing of Plasma DNA from Cancer Patients: Factors Influencing Consistency with Tumour DNA and Prospective Investigation of Its Utility for Diagnosis.

    PubMed

    Kaisaki, Pamela J; Cutts, Anthony; Popitsch, Niko; Camps, Carme; Pentony, Melissa M; Wilson, Gareth; Page, Suzanne; Kaur, Kulvinder; Vavoulis, Dimitris; Henderson, Shirley; Gupta, Avinash; Middleton, Mark R; Karydis, Ioannis; Talbot, Denis C; Schuh, Anna; Taylor, Jenny C

    2016-01-01

    Use of circulating tumour DNA (ctDNA) as a liquid biopsy has been proposed for potential identification and monitoring of solid tumours. We investigate a next-generation sequencing approach for mutation detection in ctDNA in two related studies using a targeted panel. The first study was retrospective, using blood samples taken from melanoma patients at diverse timepoints before or after treatment, aiming to evaluate correlation between mutations identified in biopsy and ctDNA, and to acquire a first impression of influencing factors. We found good concordance between ctDNA and tumour mutations of melanoma patients when blood samples were collected within one year of biopsy or before treatment. In contrast, when ctDNA was sequenced after targeted treatment in melanoma, mutations were no longer found in 9 out of 10 patients, suggesting the method might be useful for detecting treatment response. Building on these findings, we focused the second study on ctDNA obtained before biopsy in lung patients, i.e. when a tentative diagnosis of lung cancer had been made, but no treatment had started. The main objective of this prospective study was to evaluate use of ctDNA in diagnosis, investigating the concordance of biopsy and ctDNA-derived mutation detection. Here we also found positive correlation between diagnostic lung biopsy results and pre-biopsy ctDNA sequencing, providing support for using ctDNA as a cost-effective, non-invasive solution when the tumour is inaccessible or when biopsy poses significant risk to the patient. PMID:27626278

  15. Fibroblast growth factor signaling in myofibroblasts differs from lipofibroblasts during alveolar septation in mice

    PubMed Central

    McCoy, Diann M.

    2015-01-01

    Pulmonary alveolar fibroblasts produce extracellular matrix in a temporally and spatially regulated pattern to yield a durable yet pliable gas-exchange surface. Proliferation ensures a sufficient complement of cells, but they must differentiate into functionally distinct subtypes: contractile myofibroblasts (MF), which generate elastin and regulate air-flow at the alveolar ducts, and, in mice and rats, lipofibroblasts (LF), which store neutral lipids. PDGF-A is required but acts in conjunction with other differentiation factors arising from adjacent epithelia or within fibroblasts. We hypothesized that FGF receptor (FGFR) expression and function vary for MF and LF and contributes to their divergent differentiation. Whereas approximately half of the FGFR3 was extracellular in MF, FGFR2 and FGFR4 were primarily intracellular. Intracellular FGFR3 localized to the multivesicular body, and its abundance may be modified by Sprouty and interaction with heat shock protein-90. FGF18 mRNA is more abundant in MF, whereas FGF10 mRNA predominated in LF, which also express FGFR1 IIIb, a receptor for FGF10. FGF18 diminished fibroblast proliferation and was chemotactic for cultured fibroblasts. Although PDGF receptor-α (PDGFR-α) primarily signals through phosphoinositide 3-kinase and Akt, p42/p44 MAP kinase (Erk1/2), a major signaling pathway for FGFRs, influenced the abundance of cell-surface PDGFR-α. Observing different FGFR and ligand profiles in MF and LF is consistent with their divergent differentiation although both subpopulations express PDGFR-α. These studies also emphasize the importance of particular cellular locations of FGFR3 and PDGFR-α, which may modify their effects during alveolar development or repair. PMID:26138642

  16. Intensity-Modulated Proton Therapy Reduces the Dose to Normal Tissue Compared With Intensity-Modulated Radiation Therapy or Passive Scattering Proton Therapy and Enables Individualized Radical Radiotherapy for Extensive Stage IIIB Non-Small-Cell Lung Cancer: A Virtual Clinical Study

    SciTech Connect

    Zhang Xiaodong; Li Yupeng; Pan Xiaoning; Xiaoqiang, Li; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.; Chang, Joe Y.

    2010-06-01

    Purpose: To compare dose volume histograms of intensity-modulated proton therapy (IMPT) with those of intensity-modulated radiation therapy (IMRT) and passive scattering proton therapy (PSPT) for the treatment of stage IIIB non-small-cell lung cancer (NSCLC) and to explore the possibility of individualized radical radiotherapy. Methods and Materials: Dose volume histograms designed to deliver IMRT at 60 to 63 Gy, PSPT at 74 Gy, and IMPT at the same doses were compared and the use of individualized radical radiotherapy was assessed in patients with extensive stage IIIB NSCLC (n = 10 patients for each approach). These patients were selected based on their extensive disease and were considered to have no or borderline tolerance to IMRT at 60 to 63 Gy, based on the dose to normal tissue volume constraints (lung volume receiving 20 Gy [V20] of <35%, total mean lung dose <20 Gy; spinal cord dose, <45 Gy). The possibility of increasing the total tumor dose with IMPT for each patient without exceeding the dose volume constraints (maximum tolerated dose [MTD]) was also investigated. Results: Compared with IMRT, IMPT spared more lung, heart, spinal cord, and esophagus, even with dose escalation from 63 Gy to 83.5 Gy, with a mean MTD of 74 Gy. Compared with PSPT, IMPT allowed further dose escalation from 74 Gy to a mean MTD of 84.4 Gy (range, 79.4-88.4 Gy) while all parameters of normal tissue sparing were kept at lower or similar levels. In addition, IMPT prevented lower-dose target coverage in patients with complicated tumor anatomies. Conclusions: IMPT reduces the dose to normal tissue and allows individualized radical radiotherapy for extensive stage IIIB NSCLC.

  17. Human-factors engineering control-room design review/audit: Waterford 3 SES Generating Station, Louisiana Power and Light Company

    SciTech Connect

    Savage, J.W.

    1983-03-10

    A human factors engineering design review/audit of the Waterford-3 control room was performed at the site on May 10 through May 13, 1982. The report was prepared on the basis of the HFEB's review of the applicant's Preliminary Human Engineering Discrepancy (PHED) report and the human factors engineering design review performed at the site. This design review was carried out by a team from the Human Factors Engineering Branch, Division of Human Factors Safety. The review team was assisted by consultants from Lawrence Livermore National Laboratory (University of California), Livermore, California.

  18. Socio-Linguistic Factors in Second Language Lexical Knowledge: The Case of Second-Generation Children of Russian-Jewish Immigrants in Israel

    ERIC Educational Resources Information Center

    Schwartz, Mila; Kozminsky, Ely; Leikin, Mark

    2009-01-01

    The factors affecting the mastery of the host country's language by the children of immigrants are important in the study of immigration-related issues. This exploratory study analyses the possible link between parental socio-linguistic background factors (parent-child language choice, parental proficiency in L2, educational level, socio-economic…

  19. Generation of three different fragments of bound C3 with purified factor I or serum. II. Location of binding sites in the C3 Fragments for Factors B and H, complement receptors , and bovine conglutinin

    PubMed Central

    Ross, GD; Newman, SL; Lambris, JD; Devery-Pocius, JE; Cain, JA; Lackmann, PJ

    1983-01-01

    The many different recognized functions of C3 are dependent upon the ability of the activated C3 molecule both to bind covalently to protein and carbohydrate surfaces and to provide binding sites for as many as eleven different proteins. The location of the binding sites for six of these different proteins (factors B and H, complement receptors CR(1), CR(2) and CR(3) and conglutinin) was examined in the naturally occurring C3-fragments generated by C3 activation (C3b) and degradation by Factor I (iC3b, C3c, C3d,g) and trypsin (C3d). Evidence was obtained for at least four distinct binding sites in C3 for these six different C3 ligands. One binding site for B was detectable only in C3b, whereas a second binding site for H and CR(1) was detectable in both C3b and iC3b. The affinity of the binding site for H and CR(1) was charge dependent and considerably reduced in iC3b as compared to C3b. H binding to iC3b-coated sheep erythrocytes (EC3bi) was measurable only in low ionic strength buffer (4 mS). The finding that C3c-coated microspheres bound to CR(1), indicated that this second binding site was still intact in the C3c fragment. However, H binding to C3c was not examined. A third binding site in C3 for CR(2) was exposed in the d region by factor I cleavage of C3b into iC3b, and the activity of this site was unaffected by the further I cleavage of iC3b into C3d,g. Removal of the 8,000-dalton C3g fragment from C3d,g with trypsin forming C3d, resulted in reduced CR2 activity. However, because saturating amounts of monoclonal anti-C3g did not block the CR(2)-binding activity of EC3d,g, it appears unlikely that the g region of C3d,g or iC3b forms a part of the CR(2)-binding site. In addition, detergent-solubilized EC3d (C3d-OR) inhibited the CR(2)-binding activity of EC3d,g. Monocytes and neutrophils, that had been previously thought to lack CR(2) because of their inability to form EC3d rosettes, did bind EC3d,g containing greater than 5 × 10(4) C3d,g molecules per E

  20. What Are the Motivational Factors of First-Generation Minority College Students Who Overcome Their Family Histories to Pursue Higher Education?

    ERIC Educational Resources Information Center

    Blackwell, Edith; Pinder, Patrice Juliet

    2014-01-01

    The pathway to college is not equal for all students. Students from low socioeconomic backgrounds and minorities often face difficult challenges in trying to obtain a college education. Thus, this study utilized a qualitative grounded theory approach to explore and to understand how first-generation minority college students are motivated to…

  1. The Effect of Language Specific Factors on Early Written Composition: The Role of Spelling, Oral Language and Text Generation Skills in a Shallow Orthography

    ERIC Educational Resources Information Center

    Arfé, Barbara; Dockrell, Julie E.; De Bernardi, Bianca

    2016-01-01

    Spelling skills have been identified as one of the major barriers to written text production in young English writers. By contrast oral language skills and text generation have been found to be less influential in the texts produced by beginning writers. To date, our understanding of the role of spelling skills in transparent orthographies is…

  2. Factors Influencing Generation Y African Americans in Their Choice for College Education: An Empirical Case Study of Fort Valley State University Students

    ERIC Educational Resources Information Center

    Gyapong, Samuel K.; Smith, Thomas

    2012-01-01

    In an effort to assist a newly appointed Public Relations Officer to determine the most effective way to promote the institution to college-bound Generation Y African-Americans we offered to conduct a survey research of our current students. The results were very revealing and have been used successfully to increase enrollment to historically high…

  3. Steam generator performance degradation

    SciTech Connect

    Lovett, J.T.; Dow, B.L. )

    1991-09-01

    A survey was conducted to determine the range and severity of steam generator performance degradation effects experienced by PWRs in the United States. The survey results were tabulated and correlated with steam generator age and design. Operating experience at several PWRs was examined in detail. The operating experience at US PWRs was compared to that of PWRs in Japan and Germany. Possible causes for the performance degradation were postulated and evaluated. The sensitivity of steam generator output pressure to changes in various parameters (such as fouling factor, average reactor coolant temperature, and percentage of steam generator tubes plugged) was calculated. These calculations were used in the evaluation of possible causes of steam generator performance degradation. Several deposit exfoliation scenarios were evaluated in terms of the calculated effect on fouling factor trends and associated steam generator output pressure trends. 15 refs., 32 figs., 7 tabs.

  4. Chromophoric Dyads for the Light-Driven Generation of Hydrogen: Investigation of Factors in the Design of Multicomponent Photosensitizers for Proton Reduction.

    PubMed

    Ho, Po-Yu; Zheng, Bo; Mark, Daniel; Wong, Wai-Yeung; McCamant, David W; Eisenberg, Richard

    2016-09-01

    Two new dyads have been synthesized and studied as photosensitizers for the light-driven generation of H2 from aqueous protons. One of the dyads, Dy-1, consists of a strongly absorbing Bodipy (dipyrromethene-BF2) dye and a platinum diimine benzenedithiolate (bdt) charge transfer (CT) chromophore, denoted as PtN2S2. The two components are connected through an amide linkage on the bdt side of the PtN2S2 complex. The second dyad, Dy-2, contains a diketopyrrolopyrrole dye that is linked directly to the acetylide ligands of a Pt diimine bis(arylacetylide) CT chromophore. The two dyads, as well as the Pt diimine bis(arylacetylide) CT chromophore, were attached to platinized TiO2 via phosphonate groups on the diimine through sonication of the corresponding esters, and each system was examined for photosensitizer effectiveness in photochemical generation of H2 from aqueous protons and electrons supplied by ascorbic acid. Of the three photosensitizers, Dy-1 is the most active under 530 nm radiation with an initial turnover frequency of 260 h(-1) and a total of 6770 turnovers over 60 h of irradiation. When a "white" LED light source is used, samples with Dy-2 and the Pt diimine bis(arylacetylide) chromophore, while not as effective as Dy-1, perform relatively better. A key conclusion is that the presence of a strongly absorbing organic dye increases dyad photosensitizer effectiveness only if the energy of the CT excited state lies below that of the organic dye's lowest excited state; if not, the organic dye does not improve the effectiveness of the CT chromophore for promoting electron transfer and the light-driven generation of H2. The nature of the spacer between the organic dye and the charge transfer chromophore also plays a role in the effectiveness of using dyads to improve light-driven energy-storing reactions. PMID:27532323

  5. Vaccination with Irradiated Autologous Melanoma Cells Engineered to Secrete Human Granulocyte--Macrophage Colony-Stimulating Factor Generates Potent Antitumor Immunity in Patients with Metastatic Melanoma

    NASA Astrophysics Data System (ADS)

    Soiffer, Robert; Lynch, Thomas; Mihm, Martin; Jung, Ken; Rhuda, Catherine; Schmollinger, Jan C.; Hodi, F. Stephen; Liebster, Laura; Lam, Prudence; Mentzer, Steven; Singer, Samuel; Tanabe, Kenneth K.; Benedict Cosimi, A.; Duda, Rosemary; Sober, Arthur; Bhan, Atul; Daley, John; Neuberg, Donna; Parry, Gordon; Rokovich, Joseph; Richards, Laurie; Drayer, Jan; Berns, Anton; Clift, Shirley; Cohen, Lawrence K.; Mulligan, Richard C.; Dranoff, Glenn

    1998-10-01

    We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte--macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte--macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.

  6. Mixing zone and drinking water intake dilution factor and wastewater generation distributions to enable probabilistic assessment of down-the-drain consumer product chemicals in the U.S.

    PubMed

    Kapo, Katherine E; McDonough, Kathleen; Federle, Thomas; Dyer, Scott; Vamshi, Raghu

    2015-06-15

    Environmental exposure and associated ecological risk related to down-the-drain chemicals discharged by municipal wastewater treatment plants (WWTPs) are strongly influenced by in-stream dilution of receiving waters which varies by geography, flow conditions and upstream wastewater inputs. The iSTREEM® model (American Cleaning Institute, Washington D.C.) was utilized to determine probabilistic distributions for no decay and decay-based dilution factors in mean annual and low (7Q10) flow conditions. The dilution factors derived in this study are "combined" dilution factors which account for both hydrologic dilution and cumulative upstream effluent contributions that will differ depending on the rate of in-stream decay due to biodegradation, volatilization, sorption, etc. for the chemical being evaluated. The median dilution factors estimated in this study (based on various in-stream decay rates from zero decay to a 1h half-life) for WWTP mixing zones dominated by domestic wastewater flow ranged from 132 to 609 at mean flow and 5 to 25 at low flow, while median dilution factors at drinking water intakes (mean flow) ranged from 146 to 2×10(7) depending on the in-stream decay rate. WWTPs within the iSTREEM® model were used to generate a distribution of per capita wastewater generated in the U.S. The dilution factor and per capita wastewater generation distributions developed by this work can be used to conduct probabilistic exposure assessments for down-the-drain chemicals in influent wastewater, wastewater treatment plant mixing zones and at drinking water intakes in the conterminous U.S. In addition, evaluation of types and abundance of U.S. wastewater treatment processes provided insight into treatment trends and the flow volume treated by each type of process. Moreover, removal efficiencies of chemicals can differ by treatment type. Hence, the availability of distributions for per capita wastewater production, treatment type, and dilution factors at a national

  7. Ajoene, a compound of garlic, induces apoptosis in human promyeloleukemic cells, accompanied by generation of reactive oxygen species and activation of nuclear factor kappaB.

    PubMed

    Dirsch, V M; Gerbes, A L; Vollmar, A M

    1998-03-01

    The pharmacological role of garlic in prevention and treatment of cancer has received increasing attention, but thorough investigations into the molecular mechanisms of action of garlic compounds are rare. The present study demonstrates that ajoene, a major compound of garlic induces apoptosis in human leukemic cells, but not in peripheral mononuclear blood cells of healthy donors. The effect was dose and time dependent. Apoptosis was judged by three criteria, morphology of cells, quantification of subdiploid DNA content by flow cytometry, and detection of DNA fragmentation by gel electrophoresis. Ajoene increased the production of intracellular peroxide in a dose- and time-dependent fashion, which could be partially blocked by preincubation of the human leukemic cells with the antioxidant N-acetylcysteine. Interestingly, N-acetylcysteine-treated cells showed a 50% loss of ajoene-induced apoptosis. Moreover, ajoene was demonstrated to activate nuclear translocation of the transcription factor nuclear factor kappaB, an effect that was abrogated in N-acetylcysteine-loaded cells. These results suggested that ajoene might induce apoptosis in human leukemic cells via stimulation of peroxide production and activation of nuclear factor kappaB. This is a novel aspect in the biological profile of this garlic compound and an important step in elucidating the underlying molecular mechanisms of its antitumor action.

  8. Manassantin B isolated from Saururus chinensis inhibits cyclooxygenase-2-dependent prostaglandin D2 generation by blocking Fyn-mediated nuclear factor-kappaB and mitogen activated protein kinase pathways in bone marrow derived-mast cells.

    PubMed

    Lu, Yue; Hwang, Seung-Lark; Son, Jong Keun; Chang, Hyeun Wook

    2013-01-01

    The authors investigated the effect of manassantin B (Man B) isolated from Saururus chinensis (S. chinensis) on cyclooxygenase-2 (COX-2)-dependent prostaglandin D2 (PGD2) generation in mouse bone marrow derived-mast cells (BMMCs). Man B inhibited the generation of PGD2 dose-dependently by inhibiting COX-2 expression in immunoglobulin E (IgE)/Ag-stimulated BMMCs. To elucidate the mechanism responsible for the inhibition of COX-2 expression by Man B, the effects of Man B on the activation of nuclear factor-kappaB (NF-κB), a transcription factor essential and mitogen-activated protein kinases (MAPKs) for COX-2 induction, were examined. Man B attenuated the nuclear translocation of NF-κB p65 and its DNA-binding activity by inhibiting inhibitors of kappa Bα (IκBα) degradation and concomitantly suppressing IκB kinase (IKK) phosphorylation. In addition, Man B suppressed phosphorylation of MAPKs including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK) and p38. It was also found that Man B suppressed Fyn kinase activation and consequent downstream signaling processes, including those involving Syk, Gab2, and Akt. Taken together, the present results suggest that Man B suppresses COX-2 dependent PGD2 generation by primarily inhibiting Fyn kinase in FcεRI-mediated mast cells.

  9. Transforming growth factor-β2 increases the capacity of retinal pigment epithelial cells to induce the generation of regulatory T cells.

    PubMed

    Yan, Feng; He, Jin; Tang, Li; Kong, Yi; Shi, Yuhua; Chen, Suihua; Huang, Zhenping

    2016-02-01

    The present study investigated the underlying mechanism of the induction of regulatory T cells (Tregs) by retinal pigment epithelial (RPE) cells and the characteristics of these Tregs. Human RPE cells were cultured in the presence or absence of transforming growth factor-β 2 (TGF-β2), and reverse-transcription quantitative PCR was performed to determine the mRNA expression of indoleamine 2,3-dioxygenase (IDO) and nuclear factor erythroid 2-related factor (Nrf2). Supernatants of RPE cell cultures were added to CD4+ T cells to induce Tregs. The RPE-induced Tregs were purified by two-step magnetic cell sorting. The natural Tregs were isolated from the peripheral blood mononuclear cells of healthy volunteers. Purified CD4+ CD25- T cells (2 x 10(5)/well) were cultured alone or with Tregs (various densities, natural or RPE-induced). The proliferation of CD4+ CD25- T cells was determined by 3H-thymidine incorporation. After 24 h of stimulation with TGF-β2, the mRNA expression of IDO in RPE cells was upregulated. The highest level of IDO mRNA expression was reached after 72 h of stimulation with TGF-β2. However, the Nrf2 mRNA expression was slightly decreased after 24 h of stimulation with TGF-β2 and significantly increased after 48-72 h of TGF-β2 stimulation. Increased levels of CD25 expression were observed on CD4+ T cells exposed to supernatants of RPE cell cultures treated with TGF-β2 and recombinant interleukin-2. The RPE-induced Tregs were more effective at suppressing the proliferation of CD4+ CD25- T cells compared with native Tregs. These findings suggested that IDO may be a signaling protein in RPE cells which is implicated in the induction of Tregs. RPE-induced Tregs have the potential to be applied for immunotherapy for ocular inflammatory diseases.

  10. Innovative revenue generation.

    PubMed

    Pink, G H; Deber, R B; Lavoie, J N; Aserlind, E

    1991-01-01

    Innovative revenue generation by Canadian hospitals is drawing increasing attention. After a critical examination of the literature, we classified these into six areas: clinical/diagnostic insured services, clinical/diagnostic non-insured services, hotel services, retail services, administrative services and financial activities. We concluded that many Canadian hospitals are engaging in innovative revenue generation activities, the success of such activities has been mixed, there are many factors to consider when selecting revenue generation activities, many aspects of innovative revenue generation involve sophisticated business and risk management skills not traditionally required in hospital management, and implementation of many such activities requires support from the hospital board, hospital staff and medical staff.

  11. Material for electrodes of low temperature plasma generators

    DOEpatents

    Caplan, Malcolm; Vinogradov, Sergel Evge'evich; Ribin, Valeri Vasil'evich; Shekalov, Valentin Ivanovich; Rutberg, Philip Grigor'evich; Safronov, Alexi Anatol'evich

    2008-12-09

    Material for electrodes of low temperature plasma generators. The material contains a porous metal matrix impregnated with a material emitting electrons. The material uses a mixture of copper and iron powders as a porous metal matrix and a Group IIIB metal component such as Y.sub.2O.sub.3 is used as a material emitting electrons at, for example, the proportion of the components, mass %: iron: 3-30; Y.sub.2O.sub.3:0.05-1; copper: the remainder. Copper provides a high level of heat conduction and electric conductance, iron decreases intensity of copper evaporation in the process of plasma creation providing increased strength and lifetime, Y.sub.2O.sub.3 provides decreasing of electronic work function and stability of arc burning. The material can be used for producing the electrodes of low temperature AC plasma generators used for destruction of liquid organic wastes, medical wastes, and municipal wastes as well as for decontamination of low level radioactive waste, the destruction of chemical weapons, warfare toxic agents, etc.

  12. Material for electrodes of low temperature plasma generators

    DOEpatents

    Caplan, Malcolm; Vinogradov, Sergel Evge'evich; Ribin, Valeri Vasil'evich; Shekalov, Valentin Ivanovich; Rutberg, Philip Grigor'evich; Safronov, Alexi Anatol'evich; Shiryaev, Vasili Nikolaevich

    2010-03-02

    Material for electrodes of low temperature plasma generators. The material contains a porous metal matrix impregnated with a material emitting electrons. The material uses a mixture of copper and iron powders as a porous metal matrix and a Group IIIB metal component such as Y.sub.2O.sub.3 is used as a material emitting electrons at, for example, the proportion of the components, mass %: iron:3-30; Y.sub.2O.sub.3:0.05-1; copper: the remainder. Copper provides a high level of heat conduction and electric conductance, iron decreases intensity of copper evaporation in the process of plasma creation providing increased strength and lifetime, Y.sub.2O.sub.3 provides decreasing of electronic work function and stability of arc burning. The material can be used for producing the electrodes of low temperature AC plasma generators used for destruction of liquid organic wastes, medical wastes, municipal wastes as well as for decontamination of low level radioactive waste, the destruction of chemical weapons, warfare toxic agents, etc.

  13. Cleavage of the JunB transcription factor by caspases generates a carboxyl-terminal fragment that inhibits activator protein-1 transcriptional activity.

    PubMed

    Lee, Jason K H; Pearson, Joel D; Maser, Brandon E; Ingham, Robert J

    2013-07-26

    The activator protein-1 (AP-1) family transcription factor, JunB, is an important regulator of proliferation, apoptosis, differentiation, and the immune response. In this report, we show that JunB is cleaved in a caspase-dependent manner in apoptotic anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma cell lines and that ectopically expressed JunB is cleaved in murine RAW 264.7 macrophage cells treated with the NALP1b inflammasome activator, anthrax lethal toxin. In both cases, we identify aspartic acid 137 as the caspase cleavage site and demonstrate that JunB can be directly cleaved in vitro by multiple caspases at this site. Cleavage of JunB at aspartic acid 137 separates the N-terminal transactivation domain from the C-terminal DNA binding and dimerization domains, and we show that the C-terminal cleavage fragment retains both DNA binding activity and the ability to interact with AP-1 family transcription factors. Furthermore, this fragment interferes with the binding of full-length JunB to AP-1 sites and inhibits AP-1-dependent transcription. In summary, we have identified and characterized a novel mechanism of JunB post-translational modification and demonstrate that the C-terminal JunB caspase cleavage product functions as a potent inhibitor of AP-1-dependent transcription.

  14. Heterogeneity of myotubes generated by the MyoD and E12 basic helix-loop-helix transcription factors in otherwise non-differentiation growth conditions.

    PubMed

    Grubišić, Vladimir; Gottipati, Manoj K; Stout, Randy F; Grammer, J Robert; Parpura, Vladimir

    2014-02-01

    We used a synthetic biology approach to produce myotubes from mammalian C2C12 myoblasts in non-differentiation growth conditions using the expression of basic helix-loop-helix transcription factors, MyoD and E12, in various combinations and configurations. Our approach not only recapitulated the basics of muscle development and physiology, as the obtained myotubes showed qualities similar to those seen in striated muscle fibers in vivo, but also allowed for the synthesis of populations of myotubes which assumed distinct morphology, myofibrillar development and Ca(2+) dynamics. This fashioned class of biomaterials is suitable for the building blocks of soft actuators in micro-scale biomimetic robotics. This production line strategy can be embraced in reparative medicine as synthetic human myotubes with predetermined morphological/functional properties could be obtained using this very approach. This methodology can be adopted beyond striated muscle for the engineering of other tissue components/cells whose differentiation is governed by the principles of basic helix-loop-helix transcription factors, as in the case, for example, of neural or immune cell types.

  15. Granulocyte-macrophage colony stimulating factor promotes prolonged survival and the support of virulent infection by African swine fever virus of macrophages generated from porcine bone marrow and blood.

    PubMed

    Denham, S; Brookes, S M; Hutchings, G H; Parkhouse, R M

    1996-10-01

    Long-surviving cultures of non-adherent cells of the monocyte-macrophage lineage were established from the bone marrow and blood of weanling pigs by culturing cells from these tissues in the presence of recombinant porcine granulocyte-macrophage colony stimulating factor (GM-CSF). The cells increased in number, principally during the first 4 weeks of culture, bound monoclonal antibodies recognizing porcine macrophage antigens and avidly phagocytosed latex particles. The GM-CSF generated mononuclear phagocytes were highly infectible [correction of infectable] with a virulent Malawi isolate of African swine fever virus (ASFV) and able to generate levels of virus progeny similar to those produced by freshly isolated pig macrophages. The cultured cells retained their susceptibility to ASFV infection for as long as the cultures survived i.e. for up to 3 months.

  16. Influence of socio-economic factors on street litter generation in the middle east: effects of education level, age, and type of residence.

    PubMed

    Arafat, Hassan A; Al-Khatib, Issam A; Daoud, Raeda; Shwahneh, Hadeel

    2007-08-01

    Street littering is considered an important environmental health issue in the Middle East. This problem is growing steadily and is attracting great concerns within the communities. The purpose of this paper, which focuses on Nablus district (Palestinian Territory), is to measure the perception and opinion of residents toward littering, in addition to studying prevailing attitudes and practices on littering. This was achieved using an interview survey approach. The influence of three socio-economic factors; level of education, age, and type of residence, on the littering behaviour of individuals was studied. As a result, possible remedial actions have been suggested. The data presented in this work can be considered as one piece of information, which can be compiled with other future data to design an effective litter control programrhe for Middle Eastern countries.

  17. Structural factors affecting pore space transformation during hydrocarbon generation in source rock (shales): laboratory experiments and X-ray microtomography/SEM study

    NASA Astrophysics Data System (ADS)

    Giliazetdinova, Dina; Korost, Dmitry; Gerke, Kirill

    2015-04-01

    Oil and gas generation is a complex superposition of processes which take place in the interiors and are not readily observable in nature in human life time-frames. During burial of the source rocks organic matter is transformed into a mixture of high-molecular compounds - precursors of oil and gas (kerogen). Specific thermobaric conditions trigger formation of low molecular weight hydrocarbon compounds. Generation of sufficient quantities of hydrocarbons leads to the primary fluid migration. For series of our experiments we selected mainly siliceous-carbonate composition shale rocks from Domanic horizon of South-Tatar arch. Rock samples were heated in the pyrolyzer to temperatures closely corresponding to different catagenesis stages. X-ray microtomography method was used to monitor changes in the morphology of the pore space within studied shale rocks. By routine measurements we made sure that all samples (10 in total) had similar composition of organic and mineral phases. All samples in the collection were grouped according to initial structure and amount of organics and processed separately to: 1) study the influence of organic matter content on the changing morphology of the rock under thermal effects; 2) study the effect of initial structure on the primary migration processes for samples with similar organic matter content. An additional experiment was conducted to study the dynamics of changes in the structure of the pore space and prove the validity of our approach. At each stage of heating the morphology of altered rocks was characterized by formation of new pores and channels connecting primary voids. However, it was noted that the samples with a relatively low content of the organic matter had less changes in pore space morphology, in contrast to rocks with a high organic content. Second part of the study also revealed significant differences in resulting pore structures depending on initial structure of the unaltered rocks and connectivity of original

  18. Transcription from fusion promoters generated during transposition of transposon Tn4652 is positively affected by integration host factor in Pseudomonas putida.

    PubMed

    Teras, R; Hõrak, R; Kivisaar, M

    2000-02-01

    We have previously shown that both ends of the Tn3 family transposon Tn4652 contain integration host factor (IHF) binding sites and that IHF positively regulates expression of the Tn4652 transposase gene tnpA in Pseudomonas putida (R. Hõrak, and M. Kivisaar, J. Bacteriol. 180:2822-2829, 1998). Tn4652 can activate silent genes by creating fusion promoters during the transposition. The promoters are created as fusions between the -35 hexamer provided by the terminal inverted repeats of Tn4652 and the -10 hexamers in the target DNA. Two fusion promoters, PRA1 and PLA1, that contain sequences of the right and left termini of Tn4652, respectively, were chosen for the study of mechanisms of transcription activation. Gel mobility shift analysis using crude extracts from P. putida cells allowed us to detect specific binding of P. putida IHF to the ends of the transposon Tn4652. We found that the rate of transcription from the fusion promoter PRA1 is enhanced by IHF. Notably, the positive effect of IHF on transcription from the promoter PRA1 appeared only when cells of P. putida reached the stationary growth phase. We speculate that the intracellular concentration of IHF might be critical for the in vivo effect of IHF on transcription from the fusion promoters in P. putida. In the case of PLA1, the mechanism of transcription modulation by IHF is different than that observed for PRA1. Our results demonstrate that transcription of neighboring genes from outwardly directed promoters at the ends of a mobile DNA element could be influenced by the same factors that control transposition of the element. PMID:10633090

  19. Science Teacher Efficacy and Extrinsic Factors Toward Professional Development Using Video Games in a Design-Based Research Model: The Next Generation of STEM Learning

    NASA Astrophysics Data System (ADS)

    Annetta, Leonard A.; Frazier, Wendy M.; Folta, Elizabeth; Holmes, Shawn; Lamb, Richard; Cheng, Meng-Tzu

    2013-02-01

    Designed-based research principles guided the study of 51 secondary-science teachers in the second year of a 3-year professional development project. The project entailed the creation of student-centered, inquiry-based, science, video games. A professional development model appropriate for infusing innovative technologies into standards-based curricula was employed to determine how science teacher's attitudes and efficacy where impacted while designing science-based video games. The study's mixed-method design ascertained teacher efficacy on five factors (General computer use, Science Learning, Inquiry Teaching and Learning, Synchronous chat/text, and Playing Video Games) related to technology and gaming using a web-based survey). Qualitative data in the form of online blog posts was gathered during the project to assist in the triangulation and assessment of teacher efficacy. Data analyses consisted of an Analysis of Variance and serial coding of teacher reflective responses. Results indicated participants who used computers daily have higher efficacy while using inquiry-based teaching methods and science teaching and learning. Additional emergent findings revealed possible motivating factors for efficacy. This professional development project was focused on inquiry as a pedagogical strategy, standard-based science learning as means to develop content knowledge, and creating video games as technological knowledge. The project was consistent with the Technological Pedagogical Content Knowledge (TPCK) framework where overlapping circles of the three components indicates development of an integrated understanding of the suggested relationships. Findings provide suggestions for development of standards-based science education software, its integration into the curriculum and, strategies for implementing technology into teaching practices.

  20. Efficient generation of smooth muscle cells from adipose-derived stromal cells by 3D mechanical stimulation can substitute the use of growth factors in vascular tissue engineering.

    PubMed

    Parvizi, Mojtaba; Bolhuis-Versteeg, Lydia A M; Poot, André A; Harmsen, Martin C

    2016-07-01

    Occluding artery disease causes a high demand for bioartificial replacement vessels. We investigated the combined use of biodegradable and creep-free poly (1,3-trimethylene carbonate) (PTMC) with smooth muscle cells (SMC) derived by biochemical or mechanical stimulation of adipose tissue-derived stromal cells (ASC) to engineer bioartificial arteries. Biochemical induction of cultured ASC to SMC was done with TGF-β1 for 7d. Phenotype and function were assessed by qRT-PCR, immunodetection and collagen contraction assays. The influence of mechanical stimulation on non-differentiated and pre-differentiated ASC, loaded in porous tubular PTMC scaffolds, was assessed after culturing under pulsatile flow for 14d. Assays included qRT-PCR, production of extracellular matrix and scanning electron microscopy. ASC adhesion and TGF-β1-driven differentiation to contractile SMC on PTMC did not differ from tissue culture polystyrene controls. Mesenchymal and SMC markers were increased compared to controls. Interestingly, pre-differentiated ASC had only marginal higher contractility than controls. Moreover, in 3D PTMC scaffolds, mechanical stimulation yielded well-aligned ASC-derived SMC which deposited ECM. Under the same conditions, pre-differentiated ASC-derived SMC maintained their SMC phenotype. Our results show that mechanical stimulation can replace TGF-β1 pre-stimulation to generate SMC from ASC and that pre-differentiated ASC keep their SMC phenotype with increased expression of SMC markers.

  1. Neurobehavioral impairments, generation of oxidative stress and release of pro-apoptotic factors after chronic exposure to sulphur mustard in mouse brain

    SciTech Connect

    Sharma, Deep Raj; Sunkaria, Aditya; Bal, Amanjit; Bhutia, Yangchen D.; Vijayaraghavan, R.; Flora, S.J.S.; Gill, Kiran Dip

    2009-10-15

    Recent global events have focused attention on the potential threat of international and domestic chemical terrorism, as well as the possibility of chemical warfare proliferation. Sulphur mustard (SM) is one of the potent chemical warfare agents (CWA), which initiates a cascade of events that converge on the redox mechanisms common to brain injury. The present study was designed to examine the effects of chronic SM exposure on neurobehavioral impairments, mitochondrial oxidative stress in male Swiss Albino mice and its role in inducing apoptotic neuronal cell death. The animals were divided into four groups (control, low, medium and high dose) of 5 animals each. Exposure to SM was given percutaneously daily for 12 weeks. The results demonstrated impairment in neurobehavioral indices viz. rota rod, passive avoidance and water maze tests in a dose dependent manner. There was a significant increase in lipid peroxidation and protein carbonyl content whereas, decrease in the activity of manganese superoxide dismutase (MnSOD), glutathione reductase and glutathione peroxidase suggesting impaired antioxidant defense system. Immunoblotting of cytochrome c, Bcl-2, Bax and activation of caspase-3 suggest induction of apoptosis in a dose dependent manner. Finally, increased p53 expression suggests that it may target the mitochondrial pathway for inducing apoptosis in response to DNA damage signals. In conclusion, chronic SM exposure may have the potential to generate oxidative stress which may trigger the release of cytochrome c as well as caspase-3 activation in neurons leading to cell death by apoptosis in a dose dependent manner which may in the end be responsible for the disruption of cognitive functions in mice.

  2. Roles of the Yap1 transcription factor and antioxidants in Saccharomyces cerevisiae's tolerance to furfural and 5-hydroxymethylfurfural, which function as thiol-reactive electrophiles generating oxidative stress.

    PubMed

    Kim, Daehee; Hahn, Ji-Sook

    2013-08-01

    Development of the tolerance of Saccharomyces cerevisiae strains to furfural and 5-hydroxymethylfurfural (HMF) is an important issue for cellulosic ethanol production. Although furfural and HMF are known to induce oxidative stress, the underlying mechanisms are largely unknown. In this study, we show that both furfural and HMF act as thiol-reactive electrophiles, thus directly activating the Yap1 transcription factor via the H2O2-independent pathway, depleting cellular glutathione (GSH) levels, and accumulating reactive oxygen species in Saccharomyces cerevisiae. However, furfural showed higher reactivity than did HMF toward GSH in vitro and in vivo. In line with such toxic mechanisms, overexpression of YAP1(C620F), a constitutively active mutant of YAP1, and Yap1 target genes encoding catalases (CTA1 and CTT1) increased tolerance to furfural and HMF. However, increasing GSH levels by overexpression of genes for GSH biosynthesis (GSH1 and GLR1) or by the exogenous addition of GSH to the culture medium enhanced tolerance to furfural but not to HMF.

  3. Mutant p53 is a transcriptional co-factor that binds to G-rich regulatory regions of active genes and generates transcriptional plasticity

    PubMed Central

    Quante, Timo; Otto, Benjamin; Brázdová, Marie; Kejnovská, Iva; Deppert, Wolfgang; Tolstonog, Genrich V.

    2012-01-01

    The molecular mechanisms underlying mutant p53 (mutp53) “gain-of-function” (GOF) are still insufficiently understood, but there is evidence that mutp53 is a transcriptional regulator that is recruited by specialized transcription factors. Here we analyzed the binding sites of mutp53 and the epigenetic status of mutp53-regulated genes that had been identified by global expression profiling upon depletion of endogenous mutp53 (R273H) expression in U251 glioblastoma cells. We found that mutp53 preferentially and autonomously binds to G/C-rich DNA around transcription start sites (TSS) of many genes characterized by active chromatin marks (H3K4me3) and frequently associated with transcription-competent RNA polymerase II. Mutp53-bound regions overlap predominantly with CpG islands and are enriched in G4-motifs that are prone to form G-quadruplex structures. In line, mutp53 binds and stabilizes a well-characterized G-quadruplex structure in vitro. Hence, we assume that binding of mutp53 to G/C-rich DNA regions associated with a large set of cancer-relevant genes is an initial step in their regulation by mutp53. Using GAS1 and HTR2A as model genes, we show that mutp53 affects several parameters of active transcription. Finally, we discuss a dual mode model of mutp53 GOF, which includes both stochastic and deterministic components. PMID:22894900

  4. Propofol Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor-Alpha Expression and Myocardial Depression through Decreasing the Generation of Superoxide Anion in Cardiomyocytes

    PubMed Central

    Tang, Jing; Hu, Ji-Jie; Lu, Chun-Hua; Liang, Jia-Ni; Xiao, Jin-Fang; Liu, You-Tan; Lin, Chun-Shui; Qin, Zai-Sheng

    2014-01-01

    TNF-α has been shown to be a major factor responsible for myocardial depression in sepsis. The aim of this study was to investigate the effect of an anesthetic, propofol, on TNF-α expression in cardiomyocytes treated with LPS both in vivo and in vitro. In cultured cardiomyocytes, compared with control group, propofol significantly reduced protein expression of gp91phox and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) and p38 MAPK, which associates with reduced TNF-α production. In in vivo mice studies, propofol significantly improved myocardial depression and increased survival rate of mice after LPS treatment or during endotoxemia, which associates with reduced myocardial TNF-α production, gp91phox, ERK1/2, and p38 MAPK. It is concluded that propofol abrogates LPS-induced TNF-α production and alleviates cardiac depression through gp91phox/ERK1/2 or p38 MAPK signal pathway. These findings have great clinical importance in the application of propofol for patients enduring sepsis. PMID:25180066

  5. Effects of lipid and urea extraction on δ15N values of deep-sea sharks and hagfish: Can mathematical correction factors be generated?

    NASA Astrophysics Data System (ADS)

    Churchill, Diana A.; Heithaus, Michael R.; Dean Grubbs, R.

    2015-05-01

    Stable isotope analysis is broadly employed to investigate diverse ecological questions. In order to make appropriate comparisons among multiple taxa, however, it is necessary to standardize values to account for interspecific differences in factors that affect isotopic ratios. For example, varying concentrations of soluble nitrogen compounds, such as urea or trimethylamine oxide, can affect the analysis and interpretation of δ15N values of sharks or hagfish. The goal of this study was to assess the effects of a standard chloroform/methanol extraction on the stable isotope values of muscle tissue obtained from 10 species of sharks and three species of hagfish collected from poorly-known deep-water (>200 m) communities. We detected significant differences in δ15N, %N, and C:N values as a result of extractions in 8 of 10 shark and all three hagfish species. We observed increased δ15N values, but shifts in %N and C:N values were not unidirectional. Mathematical normalizations for δ15N values were successfully created for four shark and two hagfish species. However, they were not successful for two shark species. Therefore, performing extractions of all samples is recommended.

  6. P144, a Transforming Growth Factor beta inhibitor peptide, generates antitumoral effects and modifies SMAD7 and SKI levels in human glioblastoma cell lines.

    PubMed

    Gallo-Oller, Gabriel; Vollmann-Zwerenz, Arabel; Meléndez, Bárbara; Rey, Juan A; Hau, Peter; Dotor, Javier; Castresana, Javier S

    2016-10-10

    Glioblastoma (GBM) is the most prevalent malignant primary brain tumor, accounting for 60-70% of all gliomas. Current median patient survival time is 14-16 months after diagnosis. Numerous efforts in therapy have not significantly altered the nearly uniform lethality of this malignancy. The Transforming Growth Factor beta (TGF-β) signaling pathway plays a key role in GBM and is implicated in proliferation, invasion and therapy resistance. Several inhibitors of the TGF-β pathway have entered clinical trials or are under development. In this work, the therapeutic potential of P144, a TGF-β inhibitor peptide, was analyzed. P144 decreased proliferation, migration, invasiveness, and tumorigenicity in vitro, whereas apoptosis and anoikis were significantly increased for GBM cell lines. SMAD2 phosphorylation was reduced, together with a downregulation of SKI and an upregulation of SMAD7 at both transcriptional and translational levels. Additionally, P144 was able to impair tumor growth and increase survival in an in vivo flank model. Our findings suggest a potential effect of P144 in vitro and in vivo that is mediated by regulation of transcriptional target genes of the TGF-β pathway, suggesting a therapeutic potential of P144 for GBM treatment.

  7. Roles of the Yap1 transcription factor and antioxidants in Saccharomyces cerevisiae's tolerance to furfural and 5-hydroxymethylfurfural, which function as thiol-reactive electrophiles generating oxidative stress.

    PubMed

    Kim, Daehee; Hahn, Ji-Sook

    2013-08-01

    Development of the tolerance of Saccharomyces cerevisiae strains to furfural and 5-hydroxymethylfurfural (HMF) is an important issue for cellulosic ethanol production. Although furfural and HMF are known to induce oxidative stress, the underlying mechanisms are largely unknown. In this study, we show that both furfural and HMF act as thiol-reactive electrophiles, thus directly activating the Yap1 transcription factor via the H2O2-independent pathway, depleting cellular glutathione (GSH) levels, and accumulating reactive oxygen species in Saccharomyces cerevisiae. However, furfural showed higher reactivity than did HMF toward GSH in vitro and in vivo. In line with such toxic mechanisms, overexpression of YAP1(C620F), a constitutively active mutant of YAP1, and Yap1 target genes encoding catalases (CTA1 and CTT1) increased tolerance to furfural and HMF. However, increasing GSH levels by overexpression of genes for GSH biosynthesis (GSH1 and GLR1) or by the exogenous addition of GSH to the culture medium enhanced tolerance to furfural but not to HMF. PMID:23793623

  8. P144, a Transforming Growth Factor beta inhibitor peptide, generates antitumoral effects and modifies SMAD7 and SKI levels in human glioblastoma cell lines.

    PubMed

    Gallo-Oller, Gabriel; Vollmann-Zwerenz, Arabel; Meléndez, Bárbara; Rey, Juan A; Hau, Peter; Dotor, Javier; Castresana, Javier S

    2016-10-10

    Glioblastoma (GBM) is the most prevalent malignant primary brain tumor, accounting for 60-70% of all gliomas. Current median patient survival time is 14-16 months after diagnosis. Numerous efforts in therapy have not significantly altered the nearly uniform lethality of this malignancy. The Transforming Growth Factor beta (TGF-β) signaling pathway plays a key role in GBM and is implicated in proliferation, invasion and therapy resistance. Several inhibitors of the TGF-β pathway have entered clinical trials or are under development. In this work, the therapeutic potential of P144, a TGF-β inhibitor peptide, was analyzed. P144 decreased proliferation, migration, invasiveness, and tumorigenicity in vitro, whereas apoptosis and anoikis were significantly increased for GBM cell lines. SMAD2 phosphorylation was reduced, together with a downregulation of SKI and an upregulation of SMAD7 at both transcriptional and translational levels. Additionally, P144 was able to impair tumor growth and increase survival in an in vivo flank model. Our findings suggest a potential effect of P144 in vitro and in vivo that is mediated by regulation of transcriptional target genes of the TGF-β pathway, suggesting a therapeutic potential of P144 for GBM treatment. PMID:27473823

  9. Genetically engineered fusion of MAP-1 and factor H domains 1-5 generates a potent dual upstream inhibitor of both the lectin and alternative complement pathways.

    PubMed

    Nordmaj, Mie Anemone; Munthe-Fog, Lea; Hein, Estrid; Skjoedt, Mikkel-Ole; Garred, Peter

    2015-12-01

    Inhibition of the complement cascade has emerged as an option for treatment of a range of diseases. Mannose-binding lectin/ficolin/collectin-associated protein (MAP-1) is a pattern recognition molecule (PRM)-associated inhibitor of the lectin pathway. The central regulator of the alternative pathway (AP) is complement factor H (FH). Our aim was to design a dual upstream inhibitor of both human lectin and APs by fusing MAP-1 with a part of FH. There were 2 different recombinant chimeric proteins comprising full-length human MAP-1 and the first 5 N-terminal domains of human FH designed. The FH domains were orientated either in the N- or C-terminal part of MAP-1. The complement inhibition potential in human serum was assessed. Both chimeric constructs displayed the characteristics of the native molecules and bound to the PRMs with an EC50 of ∼ 2 nM. However, when added to serum diluted 1:4 in a solid-phase functional assay, only the first 5 N-terminal domains of complement FH fused to the C-terminal part of full-length MAP-1 chimeric construct were able to combine inhibition of lectin and AP activation with an half maximal inhibitory concentration of ∼ 100 and 20 nM, respectively. No effect was seen on the classical pathway. Fusion of MAP-1 with FH domains represents a novel therapeutic approach for selective targeting upstream and central complement activation at sites of inflammation.

  10. G protein coupling and second messenger generation are indispensable for metalloprotease-dependent, heparin-binding epidermal growth factor shedding through angiotensin II type-1 receptor.

    PubMed

    Mifune, Mizuo; Ohtsu, Haruhiko; Suzuki, Hiroyuki; Nakashima, Hidekatsu; Brailoiu, Eugen; Dun, Nae J; Frank, Gerald D; Inagami, Tadashi; Higashiyama, Shigeki; Thomas, Walter G; Eckhart, Andrea D; Dempsey, Peter J; Eguchi, Satoru

    2005-07-15

    A G protein-coupled receptor agonist, angiotensin II (AngII), induces epidermal growth factor (EGF) receptor (EGFR) transactivation possibly through metalloprotease-dependent, heparin-binding EGF (HB-EGF) shedding. Here, we have investigated signal transduction of this process by using COS7 cells expressing an AngII receptor, AT1. In these cells AngII-induced EGFR transactivation was completely inhibited by pretreatment with a selective HB-EGF inhibitor, or with a metalloprotease inhibitor. We also developed a COS7 cell line permanently expressing a HB-EGF construct tagged with alkaline phosphatase, which enabled us to measure HB-EGF shedding quantitatively. In the COS7 cell line AngII stimulated release of HB-EGF. This effect was mimicked by treatment either with a phospholipase C activator, a Ca2+ ionophore, a metalloprotease activator, or H2O2. Conversely, pretreatment with an intracellular Ca2+ antagonist or an antioxidant blocked AngII-induced HB-EGF shedding. Moreover, infection of an adenovirus encoding an inhibitor of G(q) markedly reduced EGFR transactivation and HB-EGF shedding through AT1. In this regard, AngII-stimulated HB-EGF shedding was abolished in an AT1 mutant that lacks G(q) protein coupling. However, in cells expressing AT1 mutants that retain G(q) protein coupling, AngII is still able to induce HB-EGF shedding. Finally, the AngII-induced EGFR transactivation was attenuated in COS7 cells overexpressing a catalytically inactive mutant of ADAM17. From these data we conclude that AngII stimulates a metalloprotease ADAM17-dependent HB-EGF shedding through AT1/G(q)/phospholipase C-mediated elevation of intracellular Ca2+ and reactive oxygen species production, representing a key mechanism indispensable for EGFR transactivation.

  11. Environmental factors influencing the structural dynamics of soil microbial communities during assisted phytostabilization of acid-generating mine tailings: a mesocosm experiment.

    PubMed

    Valentín-Vargas, Alexis; Root, Robert A; Neilson, Julia W; Chorover, Jon; Maier, Raina M

    2014-12-01

    Compost-assisted phytostabilization has recently emerged as a robust alternative for reclamation of metalliferous mine tailings. Previous studies suggest that root-associated microbes may be important for facilitating plant establishment on the tailings, yet little is known about the long-term dynamics of microbial communities during reclamation. A mechanistic understanding of microbial community dynamics in tailings ecosystems undergoing remediation is critical because these dynamics profoundly influence both the biogeochemical weathering of tailings and the sustainability of a plant cover. Here we monitor the dynamics of soil microbial communities (i.e. bacteria, fungi, archaea) during a 12-month mesocosm study that included 4 treatments: 2 unplanted controls (unamended and compost-amended tailings) and 2 compost-amended seeded tailings treatments. Bacterial, fungal and archaeal communities responded distinctively to the revegetation process and concurrent changes in environmental conditions and pore water chemistry. Compost addition significantly increased microbial diversity and had an immediate and relatively long-lasting buffering-effect on pH, allowing plants to germinate and thrive during the early stages of the experiment. However, the compost buffering capacity diminished after six months and acidification took over as the major factor affecting plant survival and microbial community structure. Immediate changes in bacterial communities were observed following plant establishment, whereas fungal communities showed a delayed response that apparently correlated with the pH decline. Fluctuations in cobalt pore water concentrations, in particular, had a significant effect on the structure of all three microbial groups, which may be linked to the role of cobalt in metal detoxification pathways. The present study represents, to our knowledge, the first documentation of the dynamics of the three major microbial groups during revegetation of compost

  12. Environmental Factors Influencing the Structural Dynamics of Soil Microbial Communities During Assisted Phytostabilization of Acid-Generating Mine Tailings: a Mesocosm Experiment

    PubMed Central

    Valentín-Vargas, Alexis; Root, Robert A.; Neilson, Julia W; Chorover, Jon; Maier, Raina M.

    2014-01-01

    Compost-assisted phytostabilization has recently emerged as a robust alternative for reclamation of metalliferous mine tailings. Previous studies suggest that root-associated microbes may be important for facilitating plant establishment on the tailings, yet little is known about the long-term dynamics of microbial communities during reclamation. A mechanistic understanding of microbial community dynamics in tailings ecosystems undergoing remediation is critical because these dynamics profoundly influence both the biogeochemical weathering of tailings and the sustainability of a plant cover. Here we monitor the dynamics of soil microbial communities (i.e. bacteria, fungi, archaea) during a 12-month mesocosm study that included 4 treatments: 2 unplanted controls (unamended and compost-amended tailings) and 2 compost-amended seeded tailings treatments. Bacterial, fungal and archaeal communities responded distinctively to the revegetation process and concurrent changes in environmental conditions and pore water chemistry. Compost addition significantly increased microbial diversity and had an immediate and relatively long-lasting buffering-effect on pH, allowing plants to germinate and thrive during the early stages of the experiment. However, the compost buffering capacity diminished after six months and acidification took over as the major factor affecting plant survival and microbial community structure. Immediate changes in bacterial communities were observed following plant establishment, whereas fungal communities showed a delayed response that apparently correlated with the pH decline. Fluctuations in cobalt pore water concentrations, in particular, had a significant effect on the structure of all three microbial groups, which may be linked to the role of cobalt in metal detoxification pathways. The present study represents, to our knowledge, the first documentation of the dynamics of the three major microbial groups during revegetation of compost

  13. Association of rat thoracic aorta dilatation by astragaloside IV with the generation of endothelium-derived hyperpolarizing factors and nitric oxide, and the blockade of Ca2+ channels

    PubMed Central

    HU, GUANYING; LI, XIXIONG; ZHANG, SANYIN; WANG, XIN

    2016-01-01

    The aim of the present study was to elucidate the roles of endothelium-derived hyperpolarizing factors (EDHFs) and nitric oxide (NO) in mediating the vasodilatation response to astragaloside IV and the effects of astragaloside IV on voltage-dependent Ca2+ channels and receptor-operated Ca2+ channels in rat thoracic aortic rings precontracted with potassium chloride (KCl; 60 mM) or phenylephrine (PHE; 1 µM). The results showed that astragaloside IV (1×10−4-3×10−1 g/l) concentration-dependently relaxed the contraction induced by KCl (10–90 mM) or PHE (1×10−9-3×10−5 µM) and inhibited concentration-contraction curves for the two vasoconstrictors in the aortic rings. Preincubation with Nω-nitro-L-arginine methyl ester (L-NAME, 100 µM) significantly attenuated astragaloside IV-induced relaxation in the endothelium-intact and -denuded arterial rings precontracted with PHE. Astragaloside IV, following preincubation with L-NAME (100 µM) plus indomethacin (10 µM), exerted vasodilatation, which was depressed by tetraethtylamine (1 mM) and propargylglycine (100 µM), but not by carbenoxolone (10 µM), catalase (500 U/ml) or proadifen hydrochloride (10 µM). The action mode of astragaloside IV was evident in comparison to nifedipine. Inhibition of PHE-induced contraction by astragaloside IV (100 mg/l) was more potent compared to inhibition of KCl-induced contraction, while inhibition of KCl-induced contraction by nifedipine (100 mg/l) was more potent compared to inhibition of PHE-induced contraction by nifedipine (100 mg/l). In addition, the combination of astragaloside IV and nifedipine exhibited synergistic and additive inhibitory effects on contraction evoked by KCl, which was similar to PHE. In conclusion, astragaloside IV, as a Ca2+ antagonist, relaxes the vessels through the blockade of superior receptor-operated Ca2+ and inferior voltage-dependent Ca2+ channels, which modulate NO from vascular endothelial cells and vascular smooth muscle cells, and

  14. Generation of fibrosarcomas in vivo by a retrovirus that expresses the normal B chain of platelet-derived growth factor and mimics the alternative splice pattern of the v-sis oncogene.

    PubMed Central

    Pech, M; Gazit, A; Arnstein, P; Aaronson, S A

    1989-01-01

    A retrovirus containing the entire human platelet-derived growth factor B-chain (PDGF-B) gene was constructed in order to investigate the in vivo biological activity of its encoded growth factor. When this virus was introduced into newborn mice, it reproducibly generated fibrosarcomas at the site of inoculation. Proviruses in each fibrosarcoma analyzed had lost 149 nucleotides downstream of the PDGF-B coding region. This deletion originated from an alternative or aberrant splice event that occurred within exon 7 of the PDGF-B gene and mimicked the v-sis oncogene. Thus, deletion of this region may be necessary for efficient retrovirus replication or for more potent transforming function. Evidence that the normal growth factor coding sequence was unaltered derived from RNase protection studies and immunoprecipitation analysis. Tumors were generally polyclonal but demonstrated clonal subpopulations. Moreover, tumor-derived cell lines became monoclonal within a few tissue culture passages and rapidly formed tumors in vivo. These findings argue that overexpression of the normal human PDGF-B gene product under retrovirus control can induce the fully malignant phenotype. Images PMID:2649890

  15. Generative Semantics

    ERIC Educational Resources Information Center

    Bagha, Karim Nazari

    2011-01-01

    Generative semantics is (or perhaps was) a research program within linguistics, initiated by the work of George Lakoff, John R. Ross, Paul Postal and later McCawley. The approach developed out of transformational generative grammar in the mid 1960s, but stood largely in opposition to work by Noam Chomsky and his students. The nature and genesis of…

  16. Generative Semantics.

    ERIC Educational Resources Information Center

    King, Margaret

    The first section of this paper deals with the attempts within the framework of transformational grammar to make semantics a systematic part of linguistic description, and outlines the characteristics of the generative semantics position. The second section takes a critical look at generative semantics in its later manifestations, and makes a case…

  17. Energy generator

    SciTech Connect

    Krisko, P.

    1989-08-01

    The patent describes a power booster. It comprises: at least one pendulum means suspended at one end to oscillate about the point of suspension; power generating means; mass means connected to one end of the pendulum means; spring means disposed in operative cooperation with the mass means to impart energy into the pendulum means and assist the pendulum means in oscillating about the point of suspension; and energy transfer linkage means between the pendulum means and the power generating means for transferring energy between the pendulum means and the power generating means.

  18. Generation Wrecked.

    ERIC Educational Resources Information Center

    Watson, Noshua

    2002-01-01

    Young adults in Generation X are facing financial problems. Because of their college and credit card debt, many in worse financial shape than anyone since the Depression and have little or no retirement savings. (JOW)

  19. Thermoelectric Generator

    NASA Technical Reports Server (NTRS)

    Cole, T.

    1985-01-01

    Small modular alkali metal thermoelectric generator with no moving parts directly converts heat to electrical energy with efficiency of 20 to 40 percent. Unit uses closed regenerative electrochemical concentration cell based on sodium-ion conductor beta alumina.

  20. Beneficial effects of omega-3 fatty acids and vitamin B12 supplementation on brain docosahexaenoic acid, brain derived neurotrophic factor, and cognitive performance in the second-generation Wistar rats.

    PubMed

    Rathod, Richa S; Khaire, Amrita A; Kale, Anvita A; Joshi, Sadhana R

    2015-01-01

    In vegetarian population, vitamin B12 deficiency coexists with suboptimal levels of omega-3 fatty acids. Studies indicate a need for supplementation/fortification of vitamin B12 and omega-3 fatty acids to reduce the risk of brain disorders. We have described the effects of vitamin B12 and omega-3 fatty acid supplementation on brain development in F1 generation animals. The current study investigates the effects of vitamin B12 and omega-3 fatty acids supplementation on brain function and cognition. Pregnant Wistar rats were assigned the following groups: control, vitamin B12 deficient (BD), vitamin B12 deficient + omega-3 fatty acid (BDO), vitamin B12 supplemented (BS), vitamin B12 supplemented + omega-3 fatty acid (BSO). The same diets were continued for two generations. BDO group showed higher (P < 0.05) levels of BDNF (brain derived neurotrophic factor) and DHA (docosahexaenoic acid) in the cortex and hippocampus as compared with the BD group. The cognitive performance was also normalized in this group. BS showed comparable levels of DHA, BDNF (protein and mRNA), and CREB mRNA (cAMP response element-binding protein) to that of control group while Tropomyosin receptor kinase mRNA levels were higher. The combined vitamin B12 and omega-3 fatty acid supplementation further enhanced the levels of DHA (P < 0.05) and BDNF (P < 0.05) in the hippocampus and CREB mRNA (P < 0.01) in the cortex as compared with BS group. The cognitive performance of these animals was higher (P < 0.05) as compared with BS group. Our data indicates the beneficial effects of vitamin B12 and omega-3 fatty acid supplementation across two generations on brain development and function.

  1. Microwave generator

    DOEpatents

    Kwan, T.J.T.; Snell, C.M.

    1987-03-31

    A microwave generator is provided for generating microwaves substantially from virtual cathode oscillation. Electrons are emitted from a cathode and accelerated to an anode which is spaced apart from the cathode. The anode has an annular slit there through effective to form the virtual cathode. The anode is at least one range thickness relative to electrons reflecting from the virtual cathode. A magnet is provided to produce an optimum magnetic field having the field strength effective to form an annular beam from the emitted electrons in substantial alignment with the annular anode slit. The magnetic field, however, does permit the reflected electrons to axially diverge from the annular beam. The reflected electrons are absorbed by the anode in returning to the real cathode, such that substantially no reflexing electrons occur. The resulting microwaves are produced with a single dominant mode and are substantially monochromatic relative to conventional virtual cathode microwave generators. 6 figs.

  2. PULSE GENERATOR

    DOEpatents

    Roeschke, C.W.

    1957-09-24

    An improvement in pulse generators is described by which there are produced pulses of a duration from about 1 to 10 microseconds with a truly flat top and extremely rapid rise and fall. The pulses are produced by triggering from a separate input or by modifying the current to operate as a free-running pulse generator. In its broad aspect, the disclosed pulse generator comprises a first tube with an anode capacitor and grid circuit which controls the firing; a second tube series connected in the cathode circuit of the first tube such that discharge of the first tube places a voltage across it as the leading edge of the desired pulse; and an integrator circuit from the plate across the grid of the second tube to control the discharge time of the second tube, determining the pulse length.

  3. (Alkylamino) piperidine bis(heteroaryl)piperizine analogs are potent, broad-spectrum nonnucleoside reverse transcriptase inhibitors of drug-resistant isolates of human immunodeficiency virus type 1 (HIV-1) and select for drug-resistant variants of HIV-1IIIB with reduced replication phenotypes.

    PubMed Central

    Olmsted, R A; Slade, D E; Kopta, L A; Poppe, S M; Poel, T J; Newport, S W; Rank, K B; Biles, C; Morge, R A; Dueweke, T J; Yagi, Y; Romero, D L; Thomas, R C; Sharma, S K; Tarpley, W G

    1996-01-01

    The (alkylamino)piperidine bis(heteroaryl)piperizines (AAP-BHAPs) are a new class of human immunodeficiency virus type 1 (HIV-1)-specific inhibitors which were identified by targeted screening of recombinant reverse transcriptase (RT) enzymes carrying key nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-conferring mutations and NNRTI-resistant variants of HIV-1. Phenotypic profiling of the two most potent AAP-BHAPs, U-95133 and U-104489, against in vitro-selected drug-resistant HIV-1 variants carrying the NNRTI resistance-conferring mutation (Tyr->Cys) at position 181 of the HIV-1 RT revealed submicromolar 90% inhibitory concentration estimates for these compounds. Moreover, U-104489 demonstrated potent activity against BHA-P-resistant HIV-1MF harboring the Pro-236->Leu RT substitution and significantly suppressed the replication of clinical isolates of HIV-1 resistant to both delavirdine (BHAP U-90152T) and zidovudine. Biochemical and phenotypic characterization of AAP-BHAPresistant HIV-1IIIB variants revealed that high-level resistance to the AAP-BHAPs was mediated by a Gly-190->Glu substitution in RT, which had a deleterious effect on the integrity and enzymatic activity of virion-associated RT heterodimers, as well as the replication capacity of these resistant viruses. PMID:8648704

  4. Smoke generator

    NASA Technical Reports Server (NTRS)

    Parrish, K. L.

    1973-01-01

    Generator is simple in construction, efficient, and extremely easy to start and regulate. It can be of such small size and weight that it can be installed easily inside a model. Size can be changed to suit needs, as long as operating temperatures can be attained and identified controls are utilized.

  5. Generation Next

    ERIC Educational Resources Information Center

    Hawkins, B. Denise

    2010-01-01

    There is a shortage of accounting professors with Ph.D.s who can prepare the next generation. To help reverse the faculty deficit, the American Institute of Certified Public Accountants (CPAs) has created the new Accounting Doctoral Scholars program by pooling more than $17 million and soliciting commitments from more than 70 of the nation's…

  6. Lung Injury and Lung Cancer Caused by Cigarette Smoke-Induced Oxidative Stress: Molecular Mechanisms and Therapeutic Opportunities Involving the Ceramide-Generating Machinery and Epidermal Growth Factor Receptor

    PubMed Central

    Filosto, Simone; Chung, Samuel

    2014-01-01

    Abstract Chronic obstructive pulmonary disease (COPD) and lung cancer are frequently caused by tobacco smoking. However, these diseases present opposite phenotypes involving redox signaling at the cellular level. While COPD is characterized by excessive airway epithelial cell death and lung injury, lung cancer is caused by uncontrolled epithelial cell proliferation. Notably, epidemiological studies have demonstrated that lung cancer incidence is significantly higher in patients who have preexisting emphysema/lung injury. However, the molecular link and common cell signaling events underlying lung injury diseases and lung cancer are poorly understood. This review focuses on studies of molecular mechanism(s) underlying smoking-related lung injury (COPD) and lung cancer. Specifically, the role of the ceramide-generating machinery during cigarette smoke-induced oxidative stress leading to both apoptosis and proliferation of lung epithelial cells is emphasized. Over recent years, it has been established that ceramide is a sphingolipid playing a major role in lung epithelia structure/function leading to lung injury in chronic pulmonary diseases. However, new and unexpected findings draw attention to its potential role in lung development, cell proliferation, and tumorigenesis. To address this dichotomy in detail, evidence is presented regarding several protein targets, including Src, p38 mitogen-activated protein kinase, and neutral sphingomyelinase 2, the major sphingomyelinase that controls ceramide generation during oxidative stress. Furthermore, their roles are presented not only in apoptosis and lung injury but also in enhancing cell proliferation, lung cancer development, and resistance to epidermal growth factor receptor-targeted therapy for treating lung cancer. Antioxid. Redox Signal. 21, 2149–2174. PMID:24684526

  7. Magnetocumulative generator

    DOEpatents

    Pettibone, J.S.; Wheeler, P.C.

    1981-06-08

    An improved magnetocumulative generator is described that is useful for producing magnetic fields of very high energy content over large spatial volumes. The polar directed pleated magnetocumulative generator has a housing providing a housing chamber with an electrically conducting surface. The chamber forms a coaxial system having a small radius portion and a large radius portion. When a magnetic field is injected into the chamber, from an external source, most of the magnetic flux associated therewith positions itself in the small radius portion. The propagation of an explosive detonation through high-explosive layers disposed adjacent to the housing causes a phased closure of the chamber which sweeps most of the magnetic flux into the large radius portion of the coaxial system. The energy content of the magnetic field is greatly increased by flux stretching as well as by flux compression. The energy enhanced magnetic field is utilized within the housing chamber itself.

  8. Humic acid in drinking well water induces inflammation through reactive oxygen species generation and activation of nuclear factor-κB/activator protein-1 signaling pathways: a possible role in atherosclerosis.

    PubMed

    Hseu, You-Cheng; Senthil Kumar, K J; Chen, Chih-Sheng; Cho, Hsin-Ju; Lin, Shu-Wei; Shen, Pei-Chun; Lin, Cheng-Wen; Lu, Fung-Jou; Yang, Hsin-Ling

    2014-01-15

    Humic acid (HA) has been implicated as one of the etiological factors in the peripheral vasculopathy of blackfoot disease (BFD) in Taiwan. However, the underlying pathophysiological mechanisms of BFD are not well defined. In this study, we used an in vitro and in vivo model, in which HA (25-200μg/mL) activated macrophages to produce pro-inflammatory molecules by activating their transcriptional factors. HA exposure induced NO and PGE2 production followed by induction of iNOS and COX-2 through NF-κB/AP-1 transactivation in macrophages. In addition, the production of TNF-α and IL-1β was significantly increased by HA. Moreover, HA-induced iNOS and COX-2 expression were down-regulated by the NF-κB and AP-1 inhibitors pyrrolidine dithiocarbamate (PDTC) and Tanshinone, respectively. Furthermore, generations of ROS and nitrotyrosine, as well as activation of the AKT and MAPKs signaling cascades were observed after HA exposure. Specifically, HA-induced NF-κB activation was mediated by ROS and AKT, and that HA-induced AP-1 activation was mediated by JNK and ERK. Notably, HA-mediated AKT, JNK, and ERK activation was ROS-independent. The inflammatory potential of HA was correlated with increased expression of HO-1 and Nrf2. Furthermore, an in vivo study confirms that mice exposed to HA, the serum levels of TNF-α and IL-1β was significantly increased in a dose-dependent manner. This report marks the first confirmation that environmental exposure of HA induces inflammation in macrophages, which may be one of the main causes of early atherogenesis in blackfoot disease.

  9. Cluster generator

    DOEpatents

    Donchev, Todor I.; Petrov, Ivan G.

    2011-05-31

    Described herein is an apparatus and a method for producing atom clusters based on a gas discharge within a hollow cathode. The hollow cathode includes one or more walls. The one or more walls define a sputtering chamber within the hollow cathode and include a material to be sputtered. A hollow anode is positioned at an end of the sputtering chamber, and atom clusters are formed when a gas discharge is generated between the hollow anode and the hollow cathode.

  10. PLASMA GENERATOR

    DOEpatents

    Foster, J.S. Jr.

    1958-03-11

    This patent describes apparatus for producing an electricity neutral ionized gas discharge, termed a plasma, substantially free from contamination with neutral gas particles. The plasma generator of the present invention comprises a plasma chamber wherein gas introduced into the chamber is ionized by a radiofrequency source. A magnetic field is used to focus the plasma in line with an exit. This magnetic field cooperates with a differential pressure created across the exit to draw a uniform and uncontaminated plasma from the plasma chamber.

  11. Thermoelectric generator

    DOEpatents

    Pryslak, N.E.

    1974-02-26

    A thermoelectric generator having a rigid coupling or stack'' between the heat source and the hot strap joining the thermoelements is described. The stack includes a member of an insulating material, such as ceramic, for electrically isolating the thermoelements from the heat source, and a pair of members of a ductile material, such as gold, one each on each side of the insulating member, to absorb thermal differential expansion stresses in the stack. (Official Gazette)

  12. Photon generator

    DOEpatents

    Srinivasan-Rao, Triveni

    2002-01-01

    A photon generator includes an electron gun for emitting an electron beam, a laser for emitting a laser beam, and an interaction ring wherein the laser beam repetitively collides with the electron beam for emitting a high energy photon beam therefrom in the exemplary form of x-rays. The interaction ring is a closed loop, sized and configured for circulating the electron beam with a period substantially equal to the period of the laser beam pulses for effecting repetitive collisions.

  13. Electric generator

    DOEpatents

    Foster, Jr., John S.; Wilson, James R.; McDonald, Jr., Charles A.

    1983-01-01

    1. In an electrical energy generator, the combination comprising a first elongated annular electrical current conductor having at least one bare surface extending longitudinally and facing radially inwards therein, a second elongated annular electrical current conductor disposed coaxially within said first conductor and having an outer bare surface area extending longitudinally and facing said bare surface of said first conductor, the contiguous coaxial areas of said first and second conductors defining an inductive element, means for applying an electrical current to at least one of said conductors for generating a magnetic field encompassing said inductive element, and explosive charge means disposed concentrically with respect to said conductors including at least the area of said inductive element, said explosive charge means including means disposed to initiate an explosive wave front in said explosive advancing longitudinally along said inductive element, said wave front being effective to progressively deform at least one of said conductors to bring said bare surfaces thereof into electrically conductive contact to progressively reduce the inductance of the inductive element defined by said conductors and transferring explosive energy to said magnetic field effective to generate an electrical potential between undeformed portions of said conductors ahead of said explosive wave front.

  14. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis

    PubMed Central

    Moghnieh, Rima; Estaitieh, Nour; Mugharbil, Anas; Jisr, Tamima; Abdallah, Dania I.; Ziade, Fouad; Sinno, Loubna; Ibrahim, Ahmad

    2015-01-01

    Introduction: Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO)-associated bacteremia. Materials and Methods: This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012. It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR) and MDRO-associated bacteremia. Results: Out of 75 bacteremias, 42.7% were gram-positive (GP), and 57.3% were gram-negative (GN). GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias). Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms) and Klebsiella pneumoniae(13.3% of total, 23.3% of GN organisms) were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS) bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO

  15. Generation Y Perspectives

    NASA Technical Reports Server (NTRS)

    Fitzpatrick, Garret; Painting, Kristen; Barrera, Aaron; Skytland, Nick

    2008-01-01

    Are you familiar with the famed Generation Y, or "Gen Yers?" Generation Y is projected to be 47 percent of the workforce by 2014. They were born roughly between 1977 and 2000, but that is definitely not their only defining factor. But who is this group, and what do they have to do with the future of the space program and the Johnson Space Center (JSC)? During 2007, a group of Gen Yers at JSC participated on a committee to address the NASA Headquarters strategic communications plan. Fitzpatrick, along with his co-authors, created a presentation to share the Gen Yers' perspective on their generation in conjunction with the strategic communications strategy released. This knowledge capture (KC) event is that presentation.

  16. Tide generator

    SciTech Connect

    Feltenberger, B.D.

    1981-06-16

    A tidewater power system consisting of a high tide reservoir and a low tide reservoir. The high tide reservoir has an inlet adapted to be supported at high tide level and an outlet with a water wheel and generator between the outlet of the high tide reservoir and the low tide reservoir. The low tide reservoir has an outlet at the low tide level. The outlet from the high tide reservoir is adjustable to control the flow rate and the high tide reservoir can be closed at high tide to retain water for use over a period of time.

  17. Smoke generator

    NASA Technical Reports Server (NTRS)

    Rogers, J. R. (Inventor)

    1976-01-01

    A smoke generator is disclosed which is particularly suitable for mounting on the wing tips of an aircraft and for conducting airflow studies. The device includes a network of thermally insulated tubes for carrying a fluid which is used to produce smoke. The fluid, which need not be combustible, is heated above its vaporization temperature by electric current which is passed through the fluid conduit tubes, so that the tubes serve both as fluid conduits and resistance heating elements. Fluid supply and monitoring systems and electrical control systems are also disclosed.

  18. HEAT GENERATION

    DOEpatents

    Imhoff, D.H.; Harker, W.H.

    1963-12-01

    Heat is generated by the utilization of high energy neutrons produced as by nuclear reactions between hydrogen isotopes in a blanket zone containing lithium, a neutron moderator, and uranium and/or thorium effective to achieve multtplicatton of the high energy neutron. The rnultiplied and moderated neutrons produced react further with lithium-6 to produce tritium in the blanket. Thermal neutron fissionable materials are also produced and consumed in situ in the blanket zone. The heat produced by the aggregate of the various nuclear reactions is then withdrawn from the blanket zone to be used or otherwise disposed externally. (AEC)

  19. Piezoelectrostatic generator

    NASA Technical Reports Server (NTRS)

    Robertson, Glen A. (Inventor)

    1990-01-01

    A piezoelectrostatic generator includes a plurality of elongated piezoelectric elements having first and second ends, with the first ends fixedly mounted in a cylindrical housing and the second extending radially inwardly toward an axis. A shaft movable along the axis is connected to the inner ends of the elements to produce bending forces in piezoelectric strips within the elements. Each element includes a pair of strips mounted in surface contact and in electrical series to produce a potential upon bending. Electrodes spaced from the strips by a solid dielectric material act as capacitor plates to collect the potential charge.

  20. Magnetocumulative generator

    DOEpatents

    Pettibone, Joseph S.; Wheeler, Paul C.

    1983-01-01

    An improved magnetocumulative generator is described that is useful for producing magnetic fields of very high energy content over large spatial volumes. The polar directed pleated magnetocumulative generator has a housing (100, 101, 102, 103, 104, 105) providing a housing chamber (106) with an electrically conducting surface. The chamber (106) forms a coaxial system having a small radius portion and a large radius portion. When a magnetic field is injected into the chamber (106), from an external source, most of the magnetic flux associated therewith positions itself in the small radius portion. The propagation of an explosive detonation through high-explosive layers (107, 108) disposed adjacent to the housing causes a phased closure of the chamber (106) which sweeps most of the magnetic flux into the large radius portion of the coaxial system. The energy content of the magnetic field is greatly increased by flux stretching as well as by flux compression. The energy enhanced magnetic field is utilized within the housing chamber itself.

  1. Inorganic pyrophosphate generation by transforming growth factor-beta-1 is mainly dependent on ANK induction by Ras/Raf-1/extracellular signal-regulated kinase pathways in chondrocytes.

    PubMed

    Cailotto, Frederic; Bianchi, Arnaud; Sebillaud, Sylvie; Venkatesan, Narayanan; Moulin, David; Jouzeau, Jean-Yves; Netter, Patrick

    2007-01-01

    ANK is a multipass transmembrane protein transporter thought to play a role in the export of intracellular inorganic pyrophosphate and so to contribute to the pathophysiology of chondrocalcinosis. As transforming growth factor-beta-1 (TGF-beta1) was shown to favor calcium pyrophosphate dihydrate deposition, we investigated the contribution of ANK to the production of extracellular inorganic pyrophosphate (ePPi) by chondrocytes and the signaling pathways involved in the regulation of Ank expression by TGF-beta1. Chondrocytes were exposed to 10 ng/mL of TGF-beta1, and Ank expression was measured by quantitative polymerase chain reaction and Western blot. ePPi was quantified in cell supernatants. RNA silencing was used to define the respective roles of Ank and PC-1 in TGF-beta1-induced ePPi generation. Finally, selective kinase inhibitors and dominant-negative/overexpression plasmid strategies were used to explore the contribution of several signaling pathways to Ank induction by TGF-beta1. TGF-beta1 strongly increased Ank expression at the mRNA and protein levels, as well as ePPi production. Using small interfering RNA technology, we showed that Ank contributed approximately 60% and PC-1 nearly 20% to TGF-beta1-induced ePPi generation. Induction of Ank by TGF-beta1 required activation of the extracellular signal-regulated kinase (ERK) pathway but not of p38-mitogen-activated protein kinase or of protein kinase A. In line with the general protein kinase C (PKC) inhibitor calphostin C, Gö6976 (a Ca2+-dependent PKC inhibitor) diminished TGF-beta1-induced Ank expression by 60%, whereas a 10% inhibition was observed with rottlerin (a PKCdelta inhibitor). These data suggest a regulatory role for calcium in TGF-beta1-induced Ank expression. Finally, we demonstrated that the stimulatory effect of TGF-beta1 on Ank expression was inhibited by the suppression of the Ras/Raf-1 pathway, while being enhanced by their constitutive activation. Transient overexpression of Smad 7, an

  2. PLASMA GENERATOR

    DOEpatents

    Wilcox, J.M.; Baker, W.R.

    1963-09-17

    This invention is a magnetohydrodynamic device for generating a highly ionized ion-electron plasma at a region remote from electrodes and structural members, thus avoiding contamination of the plasma. The apparatus utilizes a closed, gas-filled, cylindrical housing in which an axially directed magnetic field is provided. At one end of the housing, a short cylindrical electrode is disposed coaxially around a short axial inner electrode. A radial electrical discharge is caused to occur between the inner and outer electrodes, creating a rotating hydromagnetic ionization wave that propagates aiong the magnetic field lines toward the opposite end of the housing. A shorting switch connected between the electrodes prevents the wave from striking the opposite end of the housing. (AEC)

  3. Triboelectric generator

    DOEpatents

    Wang, Zhong L; Fan, Fengru; Lin, Long; Zhu, Guang; Pan, Caofeng; Zhou, Yusheng

    2015-11-03

    A generator includes a thin first contact charging layer and a thin second contact charging layer. The thin first contact charging layer includes a first material that has a first rating on a triboelectric series. The thin first contact charging layer has a first side with a first conductive electrode applied thereto and an opposite second side. The thin second contact charging layer includes a second material that has a second rating on a triboelectric series that is more negative than the first rating. The thin first contact charging layer has a first side with a first conductive electrode applied thereto and an opposite second side. The thin second contact charging layer is disposed adjacent to the first contact charging layer so that the second side of the second contact charging layer is in contact with the second side of the first contact charging layer.

  4. Humic acid in drinking well water induces inflammation through reactive oxygen species generation and activation of nuclear factor-κB/activator protein-1 signaling pathways: A possible role in atherosclerosis

    SciTech Connect

    Hseu, You-Cheng; Senthil Kumar, K.J.; Chen, Chih-Sheng; Cho, Hsin-Ju; Lin, Shu-Wei; Shen, Pei-Chun; Lin, Cheng-Wen; Lu, Fung-Jou; Yang, Hsin-Ling

    2014-01-15

    Humic acid (HA) has been implicated as one of the etiological factors in the peripheral vasculopathy of blackfoot disease (BFD) in Taiwan. However, the underlying pathophysiological mechanisms of BFD are not well defined. In this study, we used an in vitro and in vivo model, in which HA (25–200 μg/mL) activated macrophages to produce pro-inflammatory molecules by activating their transcriptional factors. HA exposure induced NO and PGE{sub 2} production followed by induction of iNOS and COX-2 through NF-κB/AP-1 transactivation in macrophages. In addition, the production of TNF-α and IL-1β was significantly increased by HA. Moreover, HA-induced iNOS and COX-2 expression were down-regulated by the NF-κB and AP-1 inhibitors pyrrolidine dithiocarbamate (PDTC) and Tanshinone, respectively. Furthermore, generations of ROS and nitrotyrosine, as well as activation of the AKT and MAPKs signaling cascades were observed after HA exposure. Specifically, HA-induced NF-κB activation was mediated by ROS and AKT, and that HA-induced AP-1 activation was mediated by JNK and ERK. Notably, HA-mediated AKT, JNK, and ERK activation was ROS-independent. The inflammatory potential of HA was correlated with increased expression of HO-1 and Nrf2. Furthermore, an in vivo study confirms that mice exposed to HA, the serum levels of TNF-α and IL-1β was significantly increased in a dose-dependent manner. This report marks the first confirmation that environmental exposure of HA induces inflammation in macrophages, which may be one of the main causes of early atherogenesis in blackfoot disease. - Highlights: • Humic acid (HA) induce pro-inflammatory cytokines and mediators in macrophages. • HA-induced inflammation is mediated by ROS and NF-κB/AP-1 signaling pathways. • The inflammatory potential of HA correlated with activation of Nrf2/HO-1 genes. • HA exposure to mice increased pro-inflammatory cytokines production in vivo. • HA may be one of the main causes of early

  5. Third-generation image intensifier

    NASA Astrophysics Data System (ADS)

    Roaux, E.; Richard, J. C.; Piaget, C.

    The general design and performance characteristics of third-generation image intensifiers are discussed. The third-generation image intensifier is a double proximity image tube with a GaAs photocathode, this photocathode being the principal difference between second- and third-generation tubes. Depending on weather conditions, night illumination, and target reflectivities, the third-generation image intensifier provides an average improvement in the range of detection of a factor of 1.5-3 (for L equal to or less than 0.001 lux).

  6. Wind generator

    SciTech Connect

    Wurtz, F.R.

    1980-01-29

    A wind operated generator is disclosed herein having a stationary frame or base rotatably supporting at least four sets of pivotal blades intended to be driven by impinging wind currents. Each set of blades operates in unison for opening and closing air passageways between adjacent ones of the blades as the sets of blades rotate about a common vertical axis. A wind direction sensor is provided which moves into the direction of the wind, and electro-mechanical or mechanical interface networks operably couple the wind direction sensor to the respective sets of blades whereby the blades are responsive to wind direction so as to be properly feathered to propel the sets of blades. By employment of the interface network, those blades that are in position to actuate or rotate the windmill will receive the full force of the wind while other blades which are not in a position to accomplish the proper operation will be turned to permit passage of the wind thereby.

  7. The comparison between pains, difficulties in function, and associating factors of patients in subtypes of temporomandibular disorders.

    PubMed

    Kino, K; Sugisaki, M; Haketa, T; Amemori, Y; Ishikawa, T; Shibuya, T; Sato, F; Amagasa, T; Shibuya, T; Tanabe, H; Yoda, T; Sakamoto, I; Omura, K; Miyaoka, H

    2005-05-01

    The aim of this study was to compare the multidimensional properties among subtypes of painful temporomandibular disorders (TMD): myofascial pain (group I), disc displacement (group II), arthralgia (group IIIa) and osteoarthritis (group IIIb). A total of 511 patients answered a battery of questionnaires, which included questions relating to intensity and duration of pain, the Japanese version of the McGill Pain Questionnaire, limitation of daily functions, the Hospital Anxiety and Depression Scale, the Eysenck Personality Questionnaire short-form and 34 items of behavioural contributing factors. Group IIIb showed significantly the highest age in all subtypes. Those in group I had higher depression scores than those in group II (P = 0.005). Group IIIa had a lower women's ratio than in group II (P = 0.001) and the patients showed a shorter pain duration than those in groups I (P = 0.000) and II (P = 0.001). Group IIIa patients also showed lower visual analogue scale (VAS) ratings for pain descriptors 'heavy' (P = 0.002) and 'tiring' (P = 0.004) than those of group I, and 'dull' (P = 0.005), 'heavy' (P = 0.001) and 'tiring' (P = 0.005) than those of group II. Group IIIa showed lower ratios of contributing factors of 'an awareness of grinding/clenching during sleep' (P = 0.000) and 'an awareness of clenching sensation when waking up at night' (P = 0.002) than those of group I, and also showed a higher ratio of 'a liking for a hard food' (P = 0.000) and lower ratio of 'talking for a long time on the telephone' (P = 0.001) than those of group II. In conclusion, although several properties were different between subtypes, the majority of them were similar in the four subtypes of TMD. PMID:15842238

  8. Saving the "Lost Generation"

    ERIC Educational Resources Information Center

    Beebe, Anthony E.

    2007-01-01

    Since the beginning of the American experience, labels have been used to describe generations. Among them are the "Puritan generation," the "greatest generation," the "baby boomer generation" and the "MTV generation." Today, people are creating a new generation--the "lost generation." The lost generation represents a large and growing population…

  9. Steam generators, turbines, and condensers. Volume six

    SciTech Connect

    Not Available

    1986-01-01

    Volume six covers steam generators (How steam is generated, steam generation in a PWR, vertical U-tube steam generators, once-through steam generators, how much steam do steam generators make.), turbines (basic turbine principles, impulse turbines, reaction turbines, turbine stages, turbine arrangements, turbine steam flow, steam admission to turbines, turbine seals and supports, turbine oil system, generators), and condensers (need for condensers, basic condenser principles, condenser arrangements, heat transfer in condensers, air removal from condensers, circulating water system, heat loss to the circulating water system, factors affecting condenser performance, condenser auxiliaries).

  10. Third generation FCCU refractories

    SciTech Connect

    Caprio, J.A.

    1986-03-01

    After four years of research and field installations, it has now been shown that the most reasonable solution to heat, abrasion and cracking problems associated with cat cracker components can best be reached using amorphous silica aggregate castables. Incorporating the traditional cement-based system established in 50% and 90% alumina refractory castables, low K-factor amorphous silica castables provide abrasion-resistant one-component linings while reducing heat loss by 20 to 25%. Above-average shock and crack resistance, which can minimize coke penetration, will also result from linings cast or gunned with this latest generation of amorphous silica castables.

  11. Internal and ancestral controls of cell-generation times

    NASA Technical Reports Server (NTRS)

    Kubitschek, H. E.

    1969-01-01

    Lateral and longitudinal correlations between related cells reveal associations between the generation times of cells for an intermediate period /three generations in bacteral cultures/. Generation times of progeny are influenced by nongenetic factors transmitted from their ancestors.

  12. Phosphors containing boron and metals of Group IIIA and IIIB

    DOEpatents

    Setlur, Anant Achyut; Srivastava, Alok Mani; Comanzo, Holly Ann; Manivannan, Venkatesan

    2006-10-31

    A phosphor comprises: (a) at least a first metal selected from the group consisting of yttrium and elements of lanthanide series other than europium; (b) at least a second metal selected from the group consisting of aluminum, gallium, indium, and scandium; (c) boron; and (d) europium. The phosphor is used in light source that comprises a UV radiation source to convert UV radiation to visible light.

  13. Why Do First-Generation Students Fail?

    ERIC Educational Resources Information Center

    Mehta, Sanjay S.; Newbold, John J.; O'Rourke, Matthew A.

    2011-01-01

    Previous studies have determined factors contributing to first-generation student success. This study finds that first-generation students are less involved, have less social and financial support, and do not show a preference for active coping strategies. First-generation students report less social and academic satisfaction as well as lower…

  14. On the Preferred Flesh Color of Japanese and Chinese and the Determining Factors —Investigation of the Younger Generation Using Method of Successive Categories and Semantic Differential Method—

    NASA Astrophysics Data System (ADS)

    Fan, Ying; Deng, Pei; Tsuruoka, Hideki; Aoki, Naokazu; Kobayashi, Hiroyuki

    The preferred flesh color was surveyed by the successive five categories method and the SD method in Japan and China to investigate its determining factors. The Chinese most preferred flesh color was more reddish than the Japanese one, while the flesh color accepted by 50% and more of the observers in China was larger in chromaticness and more yellowish than in Japan. In the determining factors for selection of the preferred color extracted by a factor analysis, a big difference between Japanese and Chinese men was observed. The first factor of the former was kind personality, whereas that of the latter was showy appearance.

  15. Bayesian Exploratory Factor Analysis

    PubMed Central

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.; Piatek, Rémi

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates from a high dimensional set of psychological measurements. PMID:25431517

  16. PointBreak: A Randomized Phase III Study of Pemetrexed Plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Stage IIIB or IV Nonsquamous Non–Small-Cell Lung Cancer

    PubMed Central

    Patel, Jyoti D.; Socinski, Mark A.; Garon, Edward B.; Reynolds, Craig H.; Spigel, David R.; Olsen, Mark R.; Hermann, Robert C.; Jotte, Robert M.; Beck, Thaddeus; Richards, Donald A.; Guba, Susan C.; Liu, Jingyi; Frimodt-Moller, Bente; John, William J.; Obasaju, Coleman K.; Pennella, Eduardo J.; Bonomi, Philip; Govindan, Ramaswamy

    2013-01-01

    Purpose PointBreak (A Study of Pemetrexed, Carboplatin and Bevacizumab in Patients With Nonsquamous Non-Small Cell Lung Cancer) compared the efficacy and safety of pemetrexed (Pem) plus carboplatin (C) plus bevacizumab (Bev) followed by pemetrexed plus bevacizumab (PemCBev) with paclitaxel (Pac) plus carboplatin (C) plus bevacizumab (Bev) followed by bevacizumab (PacCBev) in patients with advanced nonsquamous non–small-cell lung cancer (NSCLC). Patients and Methods Patients with previously untreated stage IIIB or IV nonsquamous NSCLC and Eastern Cooperative Oncology Group performance status of 0 to 1 were randomly assigned to receive pemetrexed 500 mg/m2 or paclitaxel 200 mg/m2 combined with carboplatin area under the curve 6 and bevacizumab 15 mg/kg every 3 weeks for up to four cycles. Eligible patients received maintenance until disease progression: pemetrexed plus bevacizumab (for the PemCBev group) or bevacizumab (for the PacCBev group). The primary end point of this superiority study was overall survival (OS). Results Patients were randomly assigned to PemCBev (n = 472) or PacCBev (n = 467). For PemCBev versus PacCBev, OS hazard ratio (HR) was 1.00 (median OS, 12.6 v 13.4 months; P = .949); progression-free survival (PFS) HR was 0.83 (median PFS, 6.0 v 5.6 months; P = .012); overall response rate was 34.1% versus 33.0%; and disease control rate was 65.9% versus 69.8%. Significantly more study drug–related grade 3 or 4 anemia (14.5% v 2.7%), thrombocytopenia (23.3% v 5.6%), and fatigue (10.9% v 5.0%) occurred with PemCBev; significantly more grade 3 or 4 neutropenia (40.6% v 25.8%), febrile neutropenia (4.1% v 1.4%), sensory neuropathy (4.1% v 0%), and alopecia (grade 1 or 2; 36.8% v 6.6%) occurred with PacCBev. Conclusion OS did not improve with the PemCBev regimen compared with the PacCBev regimen, although PFS was significantly improved with PemCBev. Toxicity profiles differed; both regimens demonstrated tolerability. PMID:24145346

  17. Multi-factor authentication

    SciTech Connect

    Hamlet, Jason R; Pierson, Lyndon G

    2014-10-21

    Detection and deterrence of spoofing of user authentication may be achieved by including a cryptographic fingerprint unit within a hardware device for authenticating a user of the hardware device. The cryptographic fingerprint unit includes an internal physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a PUF value. Combining logic is coupled to receive the PUF value, combines the PUF value with one or more other authentication factors to generate a multi-factor authentication value. A key generator is coupled to generate a private key and a public key based on the multi-factor authentication value while a decryptor is coupled to receive an authentication challenge posed to the hardware device and encrypted with the public key and coupled to output a response to the authentication challenge decrypted with the private key.

  18. Submersible Generator for Marine Hydrokinetics

    SciTech Connect

    Cinq-Mars, Robert S; Burke, Timothy; Irish, James; Gustafson, Brian; Kirtley, James; Alawa, Aiman

    2011-09-01

    A submersible generator was designed as a distinct and critical subassembly of marine hydrokinetics systems, specifically tidal and stream energy conversion. The generator is designed to work with both vertical and horizontal axis turbines. The final product is a high-pole-count, radial-flux, permanent magnet, rim mounted generator, initially rated at twenty kilowatts in a two-meter-per-second flow, and designed to leverage established and simple manufacturing processes. The generator was designed to work with a 3 meter by 7 meter Gorlov Helical Turbine or a marine hydrokinetic version of the FloDesign wind turbine. The team consisted of experienced motor/generator design engineers with cooperation from major US component suppliers (magnetics, coil winding and electrical steel laminations). Support for this effort was provided by Lucid Energy Technologies and FloDesign, Inc. The following tasks were completed: Identified the conditions and requirements for MHK generators. Defined a methodology for sizing and rating MHK systems. Selected an MHK generator topology and form factor. Completed electromechanical design of submersible generator capable of coupling to multiple turbine styles. Investigated MHK generator manufacturing requirements. Reviewed cost implications and financial viability. Completed final reporting and deliverables

  19. [Histology-based algorithm in the molecular diagnosis of mutations of the Epidernal Growth Factor Receptor (EGFR) in non-small cell lung cancer].

    PubMed

    Popper, Helmut; Wrba, Fritz; Gruber-Mösenbacher, Ulrike; Hulla, Wolfgang; Pirker, Robert; Hilbe, Wolfgang; Studnicka, Michael; Mohn-Staudner, Andrea; Ploner, Ferdinand

    2011-05-01

    Patients with stage IIIB and IV non-small cell lung carcinoma (NSCLC) harboring an activating mutation of the Epidermal Growth Factor Receptor (EGFR) Gene should be treated first-line with Gefitinib, an EGFR tyrosine kinase inhibitor (TKI). EGF receptor mutations are most common in adenocarcinomas, especially non-mucinous type, rare in squamous cell carcinomas and sarcomatoid carcinomas, and do not occur in neuroendocrine carcinomas. Therefore, the Pulmonary Pathology Working Group of the Austrian Society of Pathology, after intense discussions and in consensus with Oncologists and Pulmonologists, recommends a priori EGFR mutation analysis for all cases of adenocarcinoma, and for all other NSCLC upon clinical request. This will markedly reduce waiting time for those patients, which most likely will have the greatest benefit from EGFR TKI therapy.

  20. Generational Dynamics and Librarianship: Managing Generation X.

    ERIC Educational Resources Information Center

    Cooper, Julie F.; Cooper, Eric A.

    1998-01-01

    Explores the abilities of Generation X (individuals born 1961 to 1981) librarians to respond to the evolving needs of society. Highlights include age demographics, generational attributes, technology, and the seniority system. (PEN)

  1. Levelized Power Generation Cost Codes

    1996-04-30

    LPGC is a set of nine microcomputer programs for estimating power generation costs for large steam-electric power plants. These programs permit rapid evaluation using various sets of economic and technical ground rules. The levelized power generation costs calculated may be used to compare the relative economics of nuclear and coal-fired plants based on life-cycle costs. Cost calculations include capital investment cost, operation and maintenance cost, fuel cycle cost, decommissioning cost, and total levelized power generationmore » cost. These programs can be used for quick analyses of power generation costs using alternative economic parameters, such as interest rate, escalation rate, inflation rate, plant lead times, capacity factor, fuel prices, etc. The two major types of electric generating plants considered are pressurized water reactor (PWR) and pulverized coal-fired plants. Data are also provided for the Large Scale Prototype Breeder (LSPB) type liquid metal reactor.« less

  2. VARIABLE TIME-INTERVAL GENERATOR

    DOEpatents

    Gross, J.E.

    1959-10-31

    This patent relates to a pulse generator and more particularly to a time interval generator wherein the time interval between pulses is precisely determined. The variable time generator comprises two oscillators with one having a variable frequency output and the other a fixed frequency output. A frequency divider is connected to the variable oscillator for dividing its frequency by a selected factor and a counter is used for counting the periods of the fixed oscillator occurring during a cycle of the divided frequency of the variable oscillator. This defines the period of the variable oscillator in terms of that of the fixed oscillator. A circuit is provided for selecting as a time interval a predetermined number of periods of the variable oscillator. The output of the generator consists of a first pulse produced by a trigger circuit at the start of the time interval and a second pulse marking the end of the time interval produced by the same trigger circuit.

  3. Results of clot waveform analysis and thrombin generation test for a plasma-derived factor VIIa and X mixture (MC710) in haemophilia patients with inhibitors--phase I trial: 2nd report.

    PubMed

    Shirahata, A; Fukutake, K; Mimaya, J; Takamatsu, J; Shima, M; Hanabusa, H; Takedani, H; Takashima, Y; Matsushita, T; Tawa, A; Higasa, S; Takata, N; Sakai, M; Kawakami, K; Ohashi, Y; Saito, H

    2013-03-01

    We reported the results of a clinical pharmacological study of MC710 (a mixture of plasma-derived FVIIa and FX) in haemophilia patients with inhibitors during a non-haemorrhagic state. This report provides the results of a clot waveform analysis (CWA) and thrombin generation test (TGT) using blood samples obtained in this study. CWA and TGT were conducted using blood samples obtained from a pharmacokinetic and pharmacodynamic study in which MC710 (five dose rates: 20, 40, 80, 100 and 120 μg kg(-1)) was compared with NovoSeven (120 μg kg(-1)) and FEIBA (two dose rates: 50 and 75 U kg(-1)) as control drugs in 11 haemophilia patients with inhibitors without haemorrhagic symptoms. CWA showed that MC710 provided significantly greater improvement than the control drugs in activated partial thromboplastin time (APTT) at 80 μg kg(-1); maximum clot velocity and maximum clot acceleration were more enhanced by MC710 than by control drugs. TGT revealed that MC710 significantly shortened the initiation time of thrombin generation in comparison to FEIBA and induced greater thrombin generation potency than NovoSeven. It was not clear whether or not MC710 caused significant dose-dependent changes in the two measurements; however, differences between MC710 and the control drugs were clarified. MC710 was confirmed to have superior coagulation activity and thrombin productivity and is expected to have superior bypassing activity. PMID:22989180

  4. Electrical power generating system. [for windpowered generation

    NASA Technical Reports Server (NTRS)

    Nola, F. J. (Inventor)

    1981-01-01

    An alternating current power generation system adopted to inject power in an already powered power line is discussed. The power generating system solves to adjustably coup an induction motor, as a generator, to an ac power line wherein the motor and power line are connected through a triac. The triac is regulated to normally turn on at a relatively late point in each half cycle of its operation, whereby at less than operating speed, and thus when the induction motor functions as a motor rather than as a generator, power consumption from the line is substantially reduced. The principal application will be for windmill powered generation.

  5. Superconducting wind turbine generators

    NASA Astrophysics Data System (ADS)

    Abrahamsen, A. B.; Mijatovic, N.; Seiler, E.; Zirngibl, T.; Træholt, C.; Nørgård, P. B.; Pedersen, N. F.; Andersen, N. H.; Østergård, J.

    2010-03-01

    We have examined the potential of 10 MW superconducting direct drive generators to enter the European offshore wind power market and estimated that the production of about 1200 superconducting turbines until 2030 would correspond to 10% of the EU offshore market. The expected properties of future offshore turbines of 8 and 10 MW have been determined from an up-scaling of an existing 5 MW turbine and the necessary properties of the superconducting drive train are discussed. We have found that the absence of the gear box is the main benefit and the reduced weight and size is secondary. However, the main challenge of the superconducting direct drive technology is to prove that the reliability is superior to the alternative drive trains based on gearboxes or permanent magnets. A strategy of successive testing of superconducting direct drive trains in real wind turbines of 10 kW, 100 kW, 1 MW and 10 MW is suggested to secure the accumulation of reliability experience. Finally, the quantities of high temperature superconducting tape needed for a 10 kW and an extreme high field 10 MW generator are found to be 7.5 km and 1500 km, respectively. A more realistic estimate is 200-300 km of tape per 10 MW generator and it is concluded that the present production capacity of coated conductors must be increased by a factor of 36 by 2020, resulting in a ten times lower price of the tape in order to reach a realistic price level for the superconducting drive train.

  6. The graduate entry generation: a qualitative study exploring the factors influencing the career expectations and aspirations of a graduating cohort of graduate entry dental students in one London institution

    PubMed Central

    2011-01-01

    Background Dentistry in the UK has a number of new graduate-entry programmes. The aim of the study was to explore the motivation, career expectations and experiences of final year students who chose to pursue a dental career through the graduate entry programme route in one institution; and to explore if, and how, their intended career expectations and aspirations were informed by this choice. Method In-depth interviews of 14 graduate entry students in their final year of study. Data were transcribed verbatim and analysed using framework analysis. Results There were three categories of factors influencing students' choice to study dentistry through graduate entry: 'push', 'pull' and 'mediating'. Mediating factors related to students' personal concerns and circumstances, whereas push and pull factors related to features of their previous and future careers and wider social factors. Routes to Graduate Entry study comprised: 'early career changers', 'established career changers' and those pursuing 'routes to specialisation'. These routes also influenced the students' practice of dentistry, as students integrated skills in their dental studies, and encountered new challenges. Factors which students believed would influence their future careers included: vocational training; opportunities for specialisation or developing special interests and policy-related issues, together with wider professional and social concerns. The graduate entry programme was considered 'hard work' but a quick route to a professional career which had much to offer. Students' felt more could have been made of their pre-dental studies and/or experience during the programme. Factors perceived as influencing students' future contribution to dentistry included personal and social influences. Overall there was strong support for the values of the NHS and 'giving back' to the system in their future career. Conclusion Graduate entry students appear to be motivated to enter dentistry by a range of

  7. Talkin' 'bout My Generation

    ERIC Educational Resources Information Center

    Rickes, Persis C.

    2010-01-01

    The monikers are many: (1) "Generation Y"; (2) "Echo Boomers"; (3) "GenMe"; (4) the "Net Generation"; (5) "RenGen"; and (6) "Generation Next". One name that appears to be gaining currency is "Millennials," perhaps as a way to better differentiate the current generation from its predecessor, Generation X. Millennials are those individuals born…

  8. New scale factor measure

    NASA Astrophysics Data System (ADS)

    Bousso, Raphael

    2012-07-01

    The computation of probabilities in an eternally inflating universe requires a regulator or “measure.” The scale factor time measure truncates the Universe when a congruence of timelike geodesics has expanded by a fixed volume factor. This definition breaks down if the generating congruence is contracting—a serious limitation that excludes from consideration gravitationally bound regions such as our own. Here we propose a closely related regulator which is well defined in the entire spacetime. The new scale factor cutoff restricts to events with a scale factor below a given value. Since the scale factor vanishes at caustics and crunches, this cutoff always includes an infinite number of disconnected future regions. We show that this does not lead to divergences. The resulting measure combines desirable features of the old scale factor cutoff and of the light-cone time cutoff, while eliminating some of the disadvantages of each.

  9. MHD Power Generation

    ERIC Educational Resources Information Center

    Kantrowitz, Arthur; Rosa, Richard J.

    1975-01-01

    Explains the operation of the Magnetohydrodynamic (MHD) generator and advantages of the system over coal, oil or nuclear powered generators. Details the development of MHD generators in the United States and Soviet Union. (CP)

  10. Enhanced Elliptic Grid Generation

    NASA Technical Reports Server (NTRS)

    Kaul, Upender K.

    2007-01-01

    An enhanced method of elliptic grid generation has been invented. Whereas prior methods require user input of certain grid parameters, this method provides for these parameters to be determined automatically. "Elliptic grid generation" signifies generation of generalized curvilinear coordinate grids through solution of elliptic partial differential equations (PDEs). Usually, such grids are fitted to bounding bodies and used in numerical solution of other PDEs like those of fluid flow, heat flow, and electromagnetics. Such a grid is smooth and has continuous first and second derivatives (and possibly also continuous higher-order derivatives), grid lines are appropriately stretched or clustered, and grid lines are orthogonal or nearly so over most of the grid domain. The source terms in the grid-generating PDEs (hereafter called "defining" PDEs) make it possible for the grid to satisfy requirements for clustering and orthogonality properties in the vicinity of specific surfaces in three dimensions or in the vicinity of specific lines in two dimensions. The grid parameters in question are decay parameters that appear in the source terms of the inhomogeneous defining PDEs. The decay parameters are characteristic lengths in exponential- decay factors that express how the influences of the boundaries decrease with distance from the boundaries. These terms govern the rates at which distance between adjacent grid lines change with distance from nearby boundaries. Heretofore, users have arbitrarily specified decay parameters. However, the characteristic lengths are coupled with the strengths of the source terms, such that arbitrary specification could lead to conflicts among parameter values. Moreover, the manual insertion of decay parameters is cumbersome for static grids and infeasible for dynamically changing grids. In the present method, manual insertion and user specification of decay parameters are neither required nor allowed. Instead, the decay parameters are

  11. The effect of wall friction on magnetohydrodynamic generator performance

    NASA Technical Reports Server (NTRS)

    Bishop, A. R.

    1972-01-01

    The effect of wall friction on magnetohydrodynamic generator performance is determined by introduction of a wall friction factor into the one-dimensional generator equations. This addition should be useful in improving generator analysis and determining optimum generator geometry. The curves presented can be used to determine the effects of changes in wall friction and generator performance. Wall friction has an increasing effect on the Mach number increases and a decreasing effect as the pressure drop across the generator increase.

  12. Methods of Generating and Evaluating Hypertext.

    ERIC Educational Resources Information Center

    Blustein, James; Staveley, Mark S.

    2001-01-01

    Focuses on methods of generating and evaluating hypertext. Highlights include historical landmarks; nonlinearity; literary hypertext; models of hypertext; manual, automatic, and semi-automatic generation of hypertext; mathematical models for hypertext evaluation, including computing coverage and correlation; human factors in evaluation; and…

  13. Powerline Coupler for Windmill Motor/Generators

    NASA Technical Reports Server (NTRS)

    Nola, F.

    1985-01-01

    Efficiency at low windspeed increased by firing-angle control. Power coupled from wind-driven induction motor/generator to ac powerline with help from circuit. Circuit reduces power consumed by field windings thereby improving efficiency at low windspeeds. Circuit includes zerocrossing detector, ramp generator and comparator similar to those used to set firing angles for thyristors in power factor motor controllers.

  14. An analysis of factors causing the occurrence of off-design thermally induced force effects in the zone of weld joint no. 111-1 in a PGV-1000M steam generator and recommendations on excluding them

    NASA Astrophysics Data System (ADS)

    Bakirov, M. B.; Levchuk, V. I.; Povarov, V. P.; Gromov, A. F.

    2014-08-01

    Inadmissible operational flaws occurring in the critical zones of heat-transfer and mechanical equipment are commonly revealed in all nuclear power plant units both in Russia and abroad. The number of such flaws will only grow in the future because the majority of nuclear power plants have been in operation for a time that is either close to or even exceeds the assigned service life. In this connection, establishing cause-and-effect relations with regard to accelerated incipience and growth of flaws, working out compensating measures aimed at reducing operational damageability, and setting up monitoring of equipment integrity degradation of during operation are becoming the matters of utmost importance. There is a need to introduce new approaches to comprehensive diagnostics of the technical state of important nuclear power plant equipment, including continuous monitoring of its operational damageability and the extent of its loading in the most critical zones. Starting from 2011, such a monitoring system has successfully been used for the Novovoronezh NPP Unit 5 in the zone of weld joint no. 111-1 of steam generator no. 4. Based on the results from operation of this system in 2011-2013, unsteady thermally induced force effects (periodic thermal shocks and temperature abnormalities) were reveled, which had not been considered in the design, and which have an essential influence on the operational loading of this part. Based on an analysis of cause-and-effect relations pertinent to temperature abnormalities connected with technological operations, a set of measures aimed at reducing the thermally induced force loads exerted on pipeline sections was developed, which includes corrections to the process regulations for safe operation and to the operating manuals (involving changes in the algorithms for manipulating with the stop and control valves in the steam generator blowdown system).

  15. Minding the Generation Gap

    ERIC Educational Resources Information Center

    Field, John

    2011-01-01

    Generational conflict is back. After years of relative silence, and mutual ignorance, the young and old are once more at war. With youth unemployment high on the political agenda, the fortunes of the "jobless generation" are being contrasted with those of the "golden generation" of baby boomers, but is one generation really being mugged by the…

  16. Work Values across Generations

    ERIC Educational Resources Information Center

    Hansen, Jo-Ida C.; Leuty, Melanie E.

    2012-01-01

    Mainstream publication discussions of differences in generational cohorts in the workplace suggest that individuals of more recent generations, such as Generation X and Y, have different work values than do individuals of the Silent and Baby Boom generations. Although extant research suggests that age may influence work values, few of the…

  17. Generation and culture of osteoclasts

    PubMed Central

    Marino, Silvia; Logan, John G; Mellis, David; Capulli, Mattia

    2014-01-01

    Osteoclasts are highly specialized cells of haematopoietic lineage that are uniquely responsible for bone resorption. In the past, osteoclasts were isolated as mature cells from chicken long bones, or were generated using osteoblasts or stromal cells to induce osteoclast formation in total bone marrow from mice or rabbits. The Copernican revolution in osteoclast biology began with the identification of macrophage-colony stimulating factor (M-CSF) and receptor activator NFκB-ligand (RANKL ) as the key regulators of osteoclast formation, fusion and function. The availability of recombinant human and mouse M-CSF and RANKL has enabled researchers to reliably generate osteoclasts from primary monocyte/macrophage cells as well as from cell lines such as RAW 264.7. This article summarizes the most commonly used procedures for the isolation, generation and characterization of human, rodent and chicken osteoclasts in vitro. Lists of further reading and recommendations are included to facilitate a successful application by the reader. PMID:25228983

  18. Generation and culture of osteoclasts.

    PubMed

    Marino, Silvia; Logan, John G; Mellis, David; Capulli, Mattia

    2014-01-01

    Osteoclasts are highly specialized cells of haematopoietic lineage that are uniquely responsible for bone resorption. In the past, osteoclasts were isolated as mature cells from chicken long bones, or were generated using osteoblasts or stromal cells to induce osteoclast formation in total bone marrow from mice or rabbits. The Copernican revolution in osteoclast biology began with the identification of macrophage-colony stimulating factor (M-CSF) and receptor activator NFκB-ligand (RANKL ) as the key regulators of osteoclast formation, fusion and function. The availability of recombinant human and mouse M-CSF and RANKL has enabled researchers to reliably generate osteoclasts from primary monocyte/macrophage cells as well as from cell lines such as RAW 264.7. This article summarizes the most commonly used procedures for the isolation, generation and characterization of human, rodent and chicken osteoclasts in vitro. Lists of further reading and recommendations are included to facilitate a successful application by the reader. PMID:25228983

  19. Gamma ray generator

    SciTech Connect

    Firestone, Richard B; Reijonen, Jani

    2014-05-27

    An embodiment of a gamma ray generator includes a neutron generator and a moderator. The moderator is coupled to the neutron generator. The moderator includes a neutron capture material. In operation, the neutron generator produces neutrons and the neutron capture material captures at least some of the neutrons to produces gamma rays. An application of the gamma ray generator is as a source of gamma rays for calibration of gamma ray detectors.

  20. Supersonic MHD generator system

    SciTech Connect

    Rahman, M.A.

    1983-11-29

    An improved MHD electrical power generating system of the type having a MHD topping cycle and a steam generating bottoming cycle is disclosed. The system typically includes a combustion system, a conventional MHD generator and a first diffuser radiant boiler. The improvement comprises a first supersonic MHD generator and ramjet engine configuration operatively connected in series with each other and with the conventional MHD generator. The first supersonic MHD generator and ramjet engine configuration increase the power output and improve the operating efficiency of the electrical generating system. A diffuser system is also disclosed which is in fluid communication with the supersonic MHD generator and the ramjet engine for collecting bypass plasma gas to be used for heating a second radiant boiler adapted for powering a steam turbine generator.

  1. Cylindrical neutron generator

    DOEpatents

    Leung, Ka-Ngo

    2008-04-22

    A cylindrical neutron generator is formed with a coaxial RF-driven plasma ion source and target. A deuterium (or deuterium and tritium) plasma is produced by RF excitation in a cylindrical plasma ion generator using an RF antenna. A cylindrical neutron generating target is coaxial with the ion generator, separated by plasma and extraction electrodes which contain many slots. The plasma generator emanates ions radially over 360.degree. and the cylindrical target is thus irradiated by ions over its entire circumference. The plasma generator and target may be as long as desired. The plasma generator may be in the center and the neutron target on the outside, or the plasma generator may be on the outside and the target on the inside. In a nested configuration, several concentric targets and plasma generating regions are nested to increase the neutron flux.

  2. Cylindrical neutron generator

    DOEpatents

    Leung, Ka-Ngo

    2005-06-14

    A cylindrical neutron generator is formed with a coaxial RF-driven plasma ion source and target. A deuterium (or deuterium and tritium) plasma is produced by RF excitation in a cylindrical plasma ion generator using an RF antenna. A cylindrical neutron generating target is coaxial with the ion generator, separated by plasma and extraction electrodes which contain many slots. The plasma generator emanates ions radially over 360.degree. and the cylindrical target is thus irradiated by ions over its entire circumference. The plasma generator and target may be as long as desired. The plasma generator may be in the center and the neutron target on the outside, or the plasma generator may be on the outside and the target on the inside. In a nested configuration, several concentric targets and plasma generating regions are nested to increase the neutron flux.

  3. Cylindrical neutron generator

    DOEpatents

    Leung, Ka-Ngo

    2009-12-29

    A cylindrical neutron generator is formed with a coaxial RF-driven plasma ion source and target. A deuterium (or deuterium and tritium) plasma is produced by RF excitation in a cylindrical plasma ion generator using an RF antenna. A cylindrical neutron generating target is coaxial with the ion generator, separated by plasma and extraction electrodes which contain many slots. The plasma generator emanates ions radially over 360.degree. and the cylindrical target is thus irradiated by ions over its entire circumference. The plasma generator and target may be as long as desired. The plasma generator may be in the center and the neutron target on the outside, or the plasma generator may be on the outside and the target on the inside. In a nested configuration, several concentric targets and plasma generating regions are nested to increase the neutron flux.

  4. Activation of human factor IX (Christmas factor).

    PubMed

    Di Scipio, R G; Kurachi, K; Davie, E W

    1978-06-01

    Human Factor IX (Christmas factor) is a single-chain plasma glycoprotein (mol wt 57,000) that participates in the middle phase of the intrinsic pathway of blood coagulation. It is present in plasma as a zymogen and is converted to a serine protease, Factor IXabeta, by Factor XIa (activated plasma thromboplastin antecedent) in the presence of calcium ions. In the activation reaction, two internal peptide bonds are hydrolyzed in Factor IX. These cleavages occur at a specific arginyl-alanine peptide bond and a specific arginyl-valine peptide bond. This results in the release of an activation peptide (mol wt approximately equal to 11,000) from the internal region of the precursor molecule and the generation of Factor IXabeta (mol wt approximately equal to 46,000). Factor IXabeta is composed of a light chain (mol wt approximately equal to 18,000) and a heavy chain (mol wt approximately equal to 28,000), and these chains are held together by a disulfide bond(s). The light chain originates from the amino terminal portion of the precursor molecule and has an amino terminal sequence of Tyr-Asn-Ser-Gly-Lys. The heavy chain originates from the carboxyl terminal region of the precursor molecule and contains an amino terminal sequence of Val-Val-Gly-Gly-Glu. The heavy chain of Factor IXabeta also contains the active site sequence of Phe-Cys-Ala-Gly-Phe-His-Glu-Gly-Arg-Asp-Ser-Cys-Gln-Gly-Asp-SER-Gly-Gly-Pro. The active site serine residue is shown in capital letters. Factor IX is also converted to Factor IXaalpha by a protease from Russell's viper venom. This activation reaction, however, occurs in a single step and involves only the cleavage of the internal arginyl-valine peptide bond. Human Factor IXabeta was inhibited by human antithrombin III by the formation of a one-to-one complex of enzyme and inhibitor. In this reaction, the inhibitor was tightly bound to the heavy chain of the enzyme. These data indicate that the mechanism of activation of human Factor IX and its

  5. Schooling and Inequality from Generation to Generation

    ERIC Educational Resources Information Center

    Bowles, Samuel

    1972-01-01

    Shows that substantial inequality of economic opportunity exists in the U.S. and that the educational system is a major vehicle for the transmission of economic status from one generation to the next. (RJ)

  6. Endopeptidase Cleavage Generates a Functionally Distinct Isoform of C1q/Tumor Necrosis Factor-related Protein-12 (CTRP12) with an Altered Oligomeric State and Signaling Specificity*

    PubMed Central

    Wei, Zhikui; Lei, Xia; Seldin, Marcus M.; Wong, G. William

    2012-01-01

    Adipose tissue-derived adipokines are an important class of secreted metabolic regulators that mediate tissue cross-talk to control systemic energy balance. We recently described C1q/TNF-related protein-12 (CTRP12), a novel insulin-sensitizing adipokine that regulates glucose metabolism in liver and adipose tissue. However, the biochemical properties of CTRP12 and its naturally occurring cleaved isoform have not been characterized. Here, we show that CTRP12 is a secreted hormone subjected to multiple functionally relevant posttranslational modifications at highly conserved residues. For example, Asn39 is glycosylated, whereas Cys85 mediates the assembly of higher order oligomeric structure. Endopeptidase cleavage at Lys91 generates a cleaved globular gCTRP12 isoform, the expression of which is increased by insulin. PCSK3/furin was identified as the major proprotein convertase expressed by adipocytes that mediates the endogenous cleavage of CTRP12. Cleavage at Lys91 is context-dependent: mutation of the charged Arg93 to Ala on the P2′ position enhanced cleavage, and triple mutations (K90A/K91A/R93A) abolished cleavage. Importantly, the two isoforms of CTRP12 differ in oligomeric structures and are functionally distinct. The full-length protein forms trimers and larger complexes, and the cleaved isoform consisted of predominantly dimers. Whereas full-length fCTRP12 strongly activated Akt signaling in H4IIE hepatocytes and 3T3-L1 adipocytes, gCTRP12 preferentially activated MAP kinase (ERK1/2 and p38 MAPK) signaling. Further, only fCTRP12 improved insulin-stimulated glucose uptake in adipocytes. These results reveal a novel mechanism controlling signaling specificity and function of a hormone via cleavage-dependent alteration in oligomeric state. PMID:22942287

  7. Hydrogen sulfide suppresses oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 generation from macrophages via the nuclear factor κB (NF-κB) pathway.

    PubMed

    Du, Junbao; Huang, Yaqian; Yan, Hui; Zhang, Qiaoli; Zhao, Manman; Zhu, Mingzhu; Liu, Jia; Chen, Stella X; Bu, Dingfang; Tang, Chaoshu; Jin, Hongfang

    2014-04-01

    This study was designed to examine the role of hydrogen sulfide (H2S) in the generation of oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 (MCP-1) from macrophages and possible mechanisms. THP-1 cells and RAW macrophages were pretreated with sodium hydrosulfide (NaHS) and hexyl acrylate and then treated with ox-LDL. The results showed that ox-LDL treatment down-regulated the H2S/cystathionine-β-synthase pathway, with increased MCP-1 protein and mRNA expression in both THP-1 cells and RAW macrophages. Hexyl acrylate promoted ox-LDL-induced inflammation, whereas the H2S donor NaHS inhibited it. NaHS markedly suppressed NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter in ox-LDL-treated macrophages. Furthermore, NaHS decreased the ratio of free thiol groups in p65, whereas the thiol reductant DTT reversed the inhibiting effect of H2S on the p65 DNA binding activity. Most importantly, site-specific mutation of cysteine 38 to serine in p65 abolished the effect of H2S on the sulfhydration of NF-κB and ox-LDL-induced NF-κB activation. These results suggested that endogenous H2S inhibited ox-LDL-induced macrophage inflammation by suppressing NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter. The sulfhydration of free thiol group on cysteine 38 in p65 served as a molecular mechanism by which H2S inhibited NF-κB pathway activation in ox-LDL-induced macrophage inflammation.

  8. Hydrogen Sulfide Suppresses Oxidized Low-density Lipoprotein (Ox-LDL)-stimulated Monocyte Chemoattractant Protein 1 generation from Macrophages via the Nuclear Factor κB (NF-κB) Pathway*

    PubMed Central

    Du, Junbao; Huang, Yaqian; Yan, Hui; Zhang, Qiaoli; Zhao, Manman; Zhu, Mingzhu; Liu, Jia; Chen, Stella X.; Bu, Dingfang; Tang, Chaoshu; Jin, Hongfang

    2014-01-01

    This study was designed to examine the role of hydrogen sulfide (H2S) in the generation of oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 (MCP-1) from macrophages and possible mechanisms. THP-1 cells and RAW macrophages were pretreated with sodium hydrosulfide (NaHS) and hexyl acrylate and then treated with ox-LDL. The results showed that ox-LDL treatment down-regulated the H2S/cystathionine-β-synthase pathway, with increased MCP-1 protein and mRNA expression in both THP-1 cells and RAW macrophages. Hexyl acrylate promoted ox-LDL-induced inflammation, whereas the H2S donor NaHS inhibited it. NaHS markedly suppressed NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter in ox-LDL-treated macrophages. Furthermore, NaHS decreased the ratio of free thiol groups in p65, whereas the thiol reductant DTT reversed the inhibiting effect of H2S on the p65 DNA binding activity. Most importantly, site-specific mutation of cysteine 38 to serine in p65 abolished the effect of H2S on the sulfhydration of NF-κB and ox-LDL-induced NF-κB activation. These results suggested that endogenous H2S inhibited ox-LDL-induced macrophage inflammation by suppressing NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter. The sulfhydration of free thiol group on cysteine 38 in p65 served as a molecular mechanism by which H2S inhibited NF-κB pathway activation in ox-LDL-induced macrophage inflammation. PMID:24550391

  9. Refrigeration generation using expander-generator units

    NASA Astrophysics Data System (ADS)

    Klimenko, A. V.; Agababov, V. S.; Koryagin, A. V.; Baidakova, Yu. O.

    2016-05-01

    The problems of using the expander-generator unit (EGU) to generate refrigeration, along with electricity were considered. It is shown that, on the level of the temperatures of refrigeration flows using the EGU, one can provide the refrigeration supply of the different consumers: ventilation and air conditioning plants and industrial refrigerators and freezers. The analysis of influence of process parameters on the cooling power of the EGU, which depends on the parameters of the gas expansion process in the expander and temperatures of cooled environment, was carried out. The schematic diagram of refrigeration generation plant based on EGU is presented. The features and advantages of EGU to generate refrigeration compared with thermotransformer of steam compressive and absorption types were shown, namely: there is no need to use the energy generated by burning fuel to operate the EGU; beneficial use of the heat delivered to gas from the flow being cooled in equipment operating on gas; energy production along with refrigeration generation, which makes it possible to create, using EGU, the trigeneration plants without using the energy power equipment. It is shown that the level of the temperatures of refrigeration flows, which can be obtained by using the EGU on existing technological decompression stations of the transported gas, allows providing the refrigeration supply of various consumers. The information that the refrigeration capacity of an expander-generator unit not only depends on the parameters of the process of expansion of gas flowing in the expander (flow rate, temperatures and pressures at the inlet and outlet) but it is also determined by the temperature needed for a consumer and the initial temperature of the flow of the refrigeration-carrier being cooled. The conclusion was made that the expander-generator units can be used to create trigeneration plants both at major power plants and at small energy.

  10. Mechanism of metformin action in MCF-7 and MDA-MB-231 human breast cancer cells involves oxidative stress generation, DNA damage, and transforming growth factor β1 induction.

    PubMed

    Marinello, Poliana Camila; da Silva, Thamara Nishida Xavier; Panis, Carolina; Neves, Amanda Fouto; Machado, Kaliana Larissa; Borges, Fernando Henrique; Guarnier, Flávia Alessandra; Bernardes, Sara Santos; de-Freitas-Junior, Júlio Cesar Madureira; Morgado-Díaz, José Andrés; Luiz, Rodrigo Cabral; Cecchini, Rubens; Cecchini, Alessandra Lourenço

    2016-04-01

    The participation of oxidative stress in the mechanism of metformin action in breast cancer remains unclear. We investigated the effects of clinical (6 and 30 μM) and experimental concentrations of metformin (1000 and 5000 μM) in MCF-7 and in MDA-MB-231 cells, verifying cytotoxicity, oxidative stress, DNA damage, and intracellular pathways related to cell growth and survival after 24 h of drug exposure. Clinical concentrations of metformin decreased metabolic activity of MCF-7 cells in the MTT assay, which showed increased oxidative stress and DNA damage, although cell death and impairment in the proliferative capacity were observed only at higher concentrations. The reduction in metabolic activity and proliferation in MDA-MB-231 cells was present only at experimental concentrations after 24 h of drug exposition. Oxidative stress and DNA damage were induced in this cell line at experimental concentrations. The drug decreased cytoplasmic extracellular signal-regulated kinases 1 and 2 (ERK1/2) and AKT and increased nuclear p53 and cytoplasmic transforming growth factor β1 (TGF-β1) in both cell lines. These findings suggest that metformin reduces cell survival by increasing reactive oxygen species, which induce DNA damage and apoptosis. A relationship between the increase in TGF-β1 and p53 levels and the decrease in ERK1/2 and AKT was also observed. These findings suggest the mechanism of action of metformin in both breast cancer cell lineages, whereas cell line specific undergoes redox changes in the cells in which proliferation and survival signaling are modified. Taken together, these results highlight the potential clinical utility of metformin as an adjuvant during the treatment of luminal and triple-negative breast cancer. PMID:26561471

  11. Diversity and Generation X.

    PubMed

    Davis, S K

    2001-09-01

    Managing Generation X (1965-1980) to be of better service to patients and organizations is a challenge for nurse managers. This article provides action scenarios that assist in understanding diversity and generations.

  12. Quantum random number generator

    DOEpatents

    Pooser, Raphael C.

    2016-05-10

    A quantum random number generator (QRNG) and a photon generator for a QRNG are provided. The photon generator may be operated in a spontaneous mode below a lasing threshold to emit photons. Photons emitted from the photon generator may have at least one random characteristic, which may be monitored by the QRNG to generate a random number. In one embodiment, the photon generator may include a photon emitter and an amplifier coupled to the photon emitter. The amplifier may enable the photon generator to be used in the QRNG without introducing significant bias in the random number and may enable multiplexing of multiple random numbers. The amplifier may also desensitize the photon generator to fluctuations in power supplied thereto while operating in the spontaneous mode. In one embodiment, the photon emitter and amplifier may be a tapered diode amplifier.

  13. Creative Test Generators

    ERIC Educational Resources Information Center

    Vickers, F. D.

    1973-01-01

    A brief description of a test generating program which generates questions concerning the Fortran programming language in a random but guided fashion and without resorting to an item bank.'' (Author/AK)

  14. Factor XII (Hageman factor) deficiency

    MedlinePlus

    ... takes longer than normal to clot in a test tube. Factor XII deficiency is a rare inherited disorder. Symptoms There are usually no symptoms. Exams and Tests Factor XII deficiency is most often found when ...

  15. Generating Customized Verifiers for Automatically Generated Code

    NASA Technical Reports Server (NTRS)

    Denney, Ewen; Fischer, Bernd

    2008-01-01

    Program verification using Hoare-style techniques requires many logical annotations. We have previously developed a generic annotation inference algorithm that weaves in all annotations required to certify safety properties for automatically generated code. It uses patterns to capture generator- and property-specific code idioms and property-specific meta-program fragments to construct the annotations. The algorithm is customized by specifying the code patterns and integrating them with the meta-program fragments for annotation construction. However, this is difficult since it involves tedious and error-prone low-level term manipulations. Here, we describe an annotation schema compiler that largely automates this customization task using generative techniques. It takes a collection of high-level declarative annotation schemas tailored towards a specific code generator and safety property, and generates all customized analysis functions and glue code required for interfacing with the generic algorithm core, thus effectively creating a customized annotation inference algorithm. The compiler raises the level of abstraction and simplifies schema development and maintenance. It also takes care of some more routine aspects of formulating patterns and schemas, in particular handling of irrelevant program fragments and irrelevant variance in the program structure, which reduces the size, complexity, and number of different patterns and annotation schemas that are required. The improvements described here make it easier and faster to customize the system to a new safety property or a new generator, and we demonstrate this by customizing it to certify frame safety of space flight navigation code that was automatically generated from Simulink models by MathWorks' Real-Time Workshop.

  16. Use of an artificial neural network to predict risk factors of nosocomial infection in lung cancer patients.

    PubMed

    Chen, Jie; Pan, Qin-Shi; Hong, Wan-Dong; Pan, Jingye; Zhang, Wen-Hui; Xu, Gang; Wang, Yu-Min

    2014-01-01

    Statistical methods to analyze and predict the related risk factors of nosocomial infection in lung cancer patients are various, but the results are inconsistent. A total of 609 patients with lung cancer were enrolled to allow factor comparison using Student's t-test or the Mann-Whitney test or the Chi-square test. Variables that were significantly related to the presence of nosocomial infection were selected as candidates for input into the final ANN model. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the performance of the artificial neural network (ANN) model and logistic regression (LR) model. The prevalence of nosocomial infection from lung cancer in this entire study population was 20.1% (165/609), nosocomial infections occurring in sputum specimens (85.5%), followed by blood (6.73%), urine (6.0%) and pleural effusions (1.82%). It was shown that long term hospitalization (≥ 22 days, P= 0.000), poor clinical stage (IIIb and IV stage, P=0.002), older age (≥ 61 year old, P=0.023), and use the hormones were linked to nosocomial infection and the ANN model consisted of these four factors .The artificial neural network model with variables consisting of age, clinical stage, time of hospitalization, and use of hormones should be useful for predicting nosocomial infection in lung cancer cases.

  17. Understanding Generation X employees.

    PubMed

    Kupperschmidt, B R

    1998-12-01

    Understanding Generation X employees--those born between 1961 and 1981--is essential if they are to be recruited into and retained in nursing and their potential maximized. The author discusses the times, characteristics, and work values and demands of Generation X. Armed with an enhanced understanding, nurse administrators are better prepared to maximize the potential of Generation X employees.

  18. Uniform random number generators

    NASA Technical Reports Server (NTRS)

    Farr, W. R.

    1971-01-01

    Methods are presented for the generation of random numbers with uniform and normal distributions. Subprogram listings of Fortran generators for the Univac 1108, SDS 930, and CDC 3200 digital computers are also included. The generators are of the mixed multiplicative type, and the mathematical method employed is that of Marsaglia and Bray.

  19. Generation and Context Memory

    ERIC Educational Resources Information Center

    Mulligan, Neil W.; Lozito, Jeffrey P.; Rosner, Zachary A.

    2006-01-01

    Generation enhances memory for occurrence but may not enhance other aspects of memory. The present study further delineates the negative generation effect in context memory reported in N. W. Mulligan (2004). First, the negative generation effect occurred for perceptual attributes of the target item (its color and font) but not for extratarget…

  20. Motor/generator

    DOEpatents

    Hickam, Christopher Dale

    2008-05-13

    A motor/generator is provided for connecting between a transmission input shaft and an output shaft of a prime mover. The motor/generator may include a motor/generator housing, a stator mounted to the motor/generator housing, a rotor mounted at least partially within the motor/generator housing and rotatable about a rotor rotation axis, and a transmission-shaft coupler drivingly coupled to the rotor. The transmission-shaft coupler may include a clamp, which may include a base attached to the rotor and a plurality of adjustable jaws.

  1. The MCNP5 Random number generator

    SciTech Connect

    Brown, F. B.; Nagaya, Y.

    2002-01-01

    MCNP and other Monte Carlo particle transport codes use random number generators to produce random variates from a uniform distribution on the interval. These random variates are then used in subsequent sampling from probability distributions to simulate the physical behavior of particles during the transport process. This paper describes the new random number generator developed for MCNP Version 5. The new generator will optionally preserve the exact random sequence of previous versions and is entirely conformant to the Fortran-90 standard, hence completely portable. In addition, skip-ahead algorithms have been implemented to efficiently initialize the generator for new histories, a capability that greatly simplifies parallel algorithms. Further, the precision of the generator has been increased, extending the period by a factor of 10{sup 5}. Finally, the new generator has been subjected to 3 different sets of rigorous and extensive statistical tests to verify that it produces a sufficiently random sequence.

  2. Managing the new generation.

    PubMed

    Dunn-Cane, K M; Gonzalez, J L; Stewart, H P

    1999-05-01

    As the Silent Generation quickly approaches retirement, and the Baby Boomer generation moves into management and supervisory roles, a new generation is entering the workforce. Generation Xers were born between 1965 and 1975, at a time when the country experienced high prices, wage inflation, stagnant consumer demands, and increased unemployment. Perhaps as a result, newcomers to today's workforce often have different characteristics, behavioral traits, and belief systems from their predecessors. To effectively supervise and motivate individuals from this unique generation, health care managers must begin by understanding the evolutions that have shaped each generation and influenced the workforce. In doing so, managers can create a thriving multigenerational work environment and embrace supervisory concepts that attract and motivate the new generation.

  3. Solar thermoelectric generator

    DOEpatents

    Toberer, Eric S.; Baranowski, Lauryn L.; Warren, Emily L.

    2016-05-03

    Solar thermoelectric generators (STEGs) are solid state heat engines that generate electricity from concentrated sunlight. A novel detailed balance model for STEGs is provided and applied to both state-of-the-art and idealized materials. STEGs can produce electricity by using sunlight to heat one side of a thermoelectric generator. While concentrated sunlight can be used to achieve extremely high temperatures (and thus improved generator efficiency), the solar absorber also emits a significant amount of black body radiation. This emitted light is the dominant loss mechanism in these generators. In this invention, we propose a solution to this problem that eliminates virtually all of the emitted black body radiation. This enables solar thermoelectric generators to operate at higher efficiency and achieve said efficient with lower levels of optical concentration. The solution is suitable for both single and dual axis solar thermoelectric generators.

  4. Fibroblast Growth Factor Receptor-2 Expression in Thyroid Tumor Progression: Potential Diagnostic Application

    PubMed Central

    Redler, Adriano; Di Rocco, Giorgio; Giannotti, Domenico; Frezzotti, Francesca; Bernieri, Maria Giulia; Ceccarelli, Simona; D’Amici, Sirio; Vescarelli, Enrica; Mitterhofer, Anna Paola; Angeloni, Antonio; Marchese, Cinzia

    2013-01-01

    Fibroblast growth factor receptor-2 (FGFR-2) plays an important role in tumorigenesis. In thyroid cancer it has been observed a FGFR-2 down-modulation, but the role of this receptor has not been yet clarified. Therefore, we decided to examine the expression of both FGFR-2 isoform, FGFR-2-IIIb and FGFR-2-IIIc, in different histological thyroid variants such as hyperplasia, follicular adenoma and papillary carcinoma. Immunohistochemistry and quantitative Real-Time PCR analyses were performed on samples of hyperplasia, follicular adenoma and papillary carcinoma, compared with normal thyroid tissue. Thyroid hyperplasia did not show statistically significant reduction in FGFR-2 protein and mRNA levels. Interestingly, in both follicular adenoma and papillary carcinoma samples we observed a strongly reduced expression of both FGFR-2 isoforms. We speculate that FGFR-2 down-modulation might be an early event in thyroid carcinogenesis. Furthermore, we suggest the potential use of FGFR-2 as an early marker for thyroid cancer diagnosis. PMID:23977259

  5. Fibroblast growth factor receptor-2 expression in thyroid tumor progression: potential diagnostic application.

    PubMed

    Redler, Adriano; Di Rocco, Giorgio; Giannotti, Domenico; Frezzotti, Francesca; Bernieri, Maria Giulia; Ceccarelli, Simona; D'Amici, Sirio; Vescarelli, Enrica; Mitterhofer, Anna Paola; Angeloni, Antonio; Marchese, Cinzia

    2013-01-01

    Fibroblast growth factor receptor-2 (FGFR-2) plays an important role in tumorigenesis. In thyroid cancer it has been observed a FGFR-2 down-modulation, but the role of this receptor has not been yet clarified. Therefore, we decided to examine the expression of both FGFR-2 isoform, FGFR-2-IIIb and FGFR-2-IIIc, in different histological thyroid variants such as hyperplasia, follicular adenoma and papillary carcinoma. Immunohistochemistry and quantitative Real-Time PCR analyses were performed on samples of hyperplasia, follicular adenoma and papillary carcinoma, compared with normal thyroid tissue. Thyroid hyperplasia did not show statistically significant reduction in FGFR-2 protein and mRNA levels. Interestingly, in both follicular adenoma and papillary carcinoma samples we observed a strongly reduced expression of both FGFR-2 isoforms. We speculate that FGFR-2 down-modulation might be an early event in thyroid carcinogenesis. Furthermore, we suggest the potential use of FGFR-2 as an early marker for thyroid cancer diagnosis. PMID:23977259

  6. The Transcription Factor Encyclopedia

    PubMed Central

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe. PMID:22458515

  7. The transcription factor encyclopedia.

    PubMed

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I; Bolotin, Eugene; Ticoll, Amy; Cheung, Warren A; Zhang, Xiao Yu Cindy; Dickman, Christopher T D; Fulton, Debra L; Lim, Jonathan S; Schnabl, Jake M; Ramos, Oscar H P; Vasseur-Cognet, Mireille; de Leeuw, Charles N; Simpson, Elizabeth M; Ryffel, Gerhart U; Lam, Eric W-F; Kist, Ralf; Wilson, Miranda S C; Marco-Ferreres, Raquel; Brosens, Jan J; Beccari, Leonardo L; Bovolenta, Paola; Benayoun, Bérénice A; Monteiro, Lara J; Schwenen, Helma D C; Grontved, Lars; Wederell, Elizabeth; Mandrup, Susanne; Veitia, Reiner A; Chakravarthy, Harini; Hoodless, Pamela A; Mancarelli, M Michela; Torbett, Bruce E; Banham, Alison H; Reddy, Sekhar P; Cullum, Rebecca L; Liedtke, Michaela; Tschan, Mario P; Vaz, Michelle; Rizzino, Angie; Zannini, Mariastella; Frietze, Seth; Farnham, Peggy J; Eijkelenboom, Astrid; Brown, Philip J; Laperrière, David; Leprince, Dominique; de Cristofaro, Tiziana; Prince, Kelly L; Putker, Marrit; del Peso, Luis; Camenisch, Gieri; Wenger, Roland H; Mikula, Michal; Rozendaal, Marieke; Mader, Sylvie; Ostrowski, Jerzy; Rhodes, Simon J; Van Rechem, Capucine; Boulay, Gaylor; Olechnowicz, Sam W Z; Breslin, Mary B; Lan, Michael S; Nanan, Kyster K; Wegner, Michael; Hou, Juan; Mullen, Rachel D; Colvin, Stephanie C; Noy, Peter John; Webb, Carol F; Witek, Matthew E; Ferrell, Scott; Daniel, Juliet M; Park, Jason; Waldman, Scott A; Peet, Daniel J; Taggart, Michael; Jayaraman, Padma-Sheela; Karrich, Julien J; Blom, Bianca; Vesuna, Farhad; O'Geen, Henriette; Sun, Yunfu; Gronostajski, Richard M; Woodcroft, Mark W; Hough, Margaret R; Chen, Edwin; Europe-Finner, G Nicholas; Karolczak-Bayatti, Magdalena; Bailey, Jarrod; Hankinson, Oliver; Raman, Venu; LeBrun, David P; Biswal, Shyam; Harvey, Christopher J; DeBruyne, Jason P; Hogenesch, John B; Hevner, Robert F; Héligon, Christophe; Luo, Xin M; Blank, Marissa Cathleen; Millen, Kathleen Joyce; Sharlin, David S; Forrest, Douglas; Dahlman-Wright, Karin; Zhao, Chunyan; Mishima, Yuriko; Sinha, Satrajit; Chakrabarti, Rumela; Portales-Casamar, Elodie; Sladek, Frances M; Bradley, Philip H; Wasserman, Wyeth W

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.

  8. Multiple Exciton Generation Solar Cells

    SciTech Connect

    Luther, J. M.; Semonin, O. E.; Beard, M. C.; Gao, J.; Nozik, A. J.

    2012-01-01

    Heat loss is the major factor limiting traditional single junction solar cells to a theoretical efficiency of 32%. Multiple Exciton Generation (MEG) enables efficient use of the solar spectrum yielding a theoretical power conversion efficiency of 44% in solar cells under 1-sun conditions. Quantum-confined semiconductors have demonstrated the ability to generate multiple carriers but present-day materials deliver efficiencies far below the SQ limit of 32%. Semiconductor quantum dots of PbSe and PbS provide an active testbed for developing high-efficiency, inexpensive solar cells benefitting from quantum confinement effects. Here, we will present recent work of solar cells employing MEG to yield external quantum efficiencies exceeding 100%.

  9. Modulation compression for short wavelength harmonic generation

    SciTech Connect

    Qiang, J.

    2010-01-11

    Laser modulator is used to seed free electron lasers. In this paper, we propose a scheme to compress the initial laser modulation in the longitudinal phase space by using two opposite sign bunch compressors and two opposite sign energy chirpers. This scheme could potentially reduce the initial modulation wavelength by a factor of C and increase the energy modulation amplitude by a factor of C, where C is the compression factor of the first bunch compressor. Such a compressed energy modulation can be directly used to generate short wavelength current modulation with a large bunching factor.

  10. Steam generator support system

    DOEpatents

    Moldenhauer, James E.

    1987-01-01

    A support system for connection to an outer surface of a J-shaped steam generator for use with a nuclear reactor or other liquid metal cooled power source. The J-shaped steam generator is mounted with the bent portion at the bottom. An arrangement of elongated rod members provides both horizontal and vertical support for the steam generator. The rod members are interconnected to the steam generator assembly and a support structure in a manner which provides for thermal distortion of the steam generator without the transfer of bending moments to the support structure and in a like manner substantially minimizes forces being transferred between the support structure and the steam generator as a result of seismic disturbances.

  11. Steam generator support system

    DOEpatents

    Moldenhauer, J.E.

    1987-08-25

    A support system for connection to an outer surface of a J-shaped steam generator for use with a nuclear reactor or other liquid metal cooled power source is disclosed. The J-shaped steam generator is mounted with the bent portion at the bottom. An arrangement of elongated rod members provides both horizontal and vertical support for the steam generator. The rod members are interconnected to the steam generator assembly and a support structure in a manner which provides for thermal distortion of the steam generator without the transfer of bending moments to the support structure and in a like manner substantially minimizes forces being transferred between the support structure and the steam generator as a result of seismic disturbances. 4 figs.

  12. Method of grid generation

    DOEpatents

    Barnette, Daniel W.

    2002-01-01

    The present invention provides a method of grid generation that uses the geometry of the problem space and the governing relations to generate a grid. The method can generate a grid with minimized discretization errors, and with minimal user interaction. The method of the present invention comprises assigning grid cell locations so that, when the governing relations are discretized using the grid, at least some of the discretization errors are substantially zero. Conventional grid generation is driven by the problem space geometry; grid generation according to the present invention is driven by problem space geometry and by governing relations. The present invention accordingly can provide two significant benefits: more efficient and accurate modeling since discretization errors are minimized, and reduced cost grid generation since less human interaction is required.

  13. Quantum random number generation

    DOE PAGES

    Ma, Xiongfeng; Yuan, Xiao; Cao, Zhu; Zhang, Zhen; Qi, Bing

    2016-06-28

    Here, quantum physics can be exploited to generate true random numbers, which play important roles in many applications, especially in cryptography. Genuine randomness from the measurement of a quantum system reveals the inherent nature of quantumness -- coherence, an important feature that differentiates quantum mechanics from classical physics. The generation of genuine randomness is generally considered impossible with only classical means. Based on the degree of trustworthiness on devices, quantum random number generators (QRNGs) can be grouped into three categories. The first category, practical QRNG, is built on fully trusted and calibrated devices and typically can generate randomness at amore » high speed by properly modeling the devices. The second category is self-testing QRNG, where verifiable randomness can be generated without trusting the actual implementation. The third category, semi-self-testing QRNG, is an intermediate category which provides a tradeoff between the trustworthiness on the device and the random number generation speed.« less

  14. The next generation HAPPEX experiments

    SciTech Connect

    Richard S. Holmes

    2005-02-01

    A new generation of parity violating electron scattering experiments began running in Summer 2004 at the Thomas Jefferson National Accelerator Facility. HAPPEX-H will measure the parity violating asymmetry in polarized electron scattering from protons at Q2 = 0.11 (GeV/c)2. This asymmetry is sensitive to a linear combination of the strange electric and magnetic form factors of the proton. HAPPEX-He will measure the parity violating asymmetry in polarized electron scattering from a 4He target at the same value of Q2, using the same spectrometers and similar detectors, accessing the strange electric form factor cleanly. PREX will use parity violating electron scattering to determine the neutron radius of the 206Pb nucleus.

  15. Solar fuels generator

    DOEpatents

    Lewis, Nathan S.; Spurgeon, Joshua M.

    2016-10-25

    The solar fuels generator includes an ionically conductive separator between a gaseous first phase and a second phase. A photoanode uses one or more components of the first phase to generate cations during operation of the solar fuels generator. A cation conduit is positioned provides a pathway along which the cations travel from the photoanode to the separator. The separator conducts the cations. A second solid cation conduit conducts the cations from the separator to a photocathode.

  16. Distributed generation systems model

    SciTech Connect

    Barklund, C.R.

    1994-12-31

    A slide presentation is given on a distributed generation systems model developed at the Idaho National Engineering Laboratory, and its application to a situation within the Idaho Power Company`s service territory. The objectives of the work were to develop a screening model for distributed generation alternatives, to develop a better understanding of distributed generation as a utility resource, and to further INEL`s understanding of utility concerns in implementing technological change.

  17. Modular Stirling Radioisotope Generator

    NASA Technical Reports Server (NTRS)

    Schmitz, Paul C.; Mason, Lee S.; Schifer, Nicholas A.

    2016-01-01

    High-efficiency radioisotope power generators will play an important role in future NASA space exploration missions. Stirling Radioisotope Generators (SRGs) have been identified as a candidate generator technology capable of providing mission designers with an efficient, high-specific-power electrical generator. SRGs high conversion efficiency has the potential to extend the limited Pu-238 supply when compared with current Radioisotope Thermoelectric Generators (RTGs). Due to budgetary constraints, the Advanced Stirling Radioisotope Generator (ASRG) was canceled in the fall of 2013. Over the past year a joint study by NASA and the Department of Energy (DOE) called the Nuclear Power Assessment Study (NPAS) recommended that Stirling technologies continue to be explored. During the mission studies of the NPAS, spare SRGs were sometimes required to meet mission power system reliability requirements. This led to an additional mass penalty and increased isotope consumption levied on certain SRG-based missions. In an attempt to remove the spare power system, a new generator architecture is considered, which could increase the reliability of a Stirling generator and provide a more fault-tolerant power system. This new generator called the Modular Stirling Radioisotope Generator (MSRG) employs multiple parallel Stirling convertor/controller strings, all of which share the heat from the General Purpose Heat Source (GPHS) modules. For this design, generators utilizing one to eight GPHS modules were analyzed, which provided about 50 to 450 W of direct current (DC) to the spacecraft, respectively. Four Stirling convertors are arranged around each GPHS module resulting in from 4 to 32 Stirling/controller strings. The convertors are balanced either individually or in pairs, and are radiatively coupled to the GPHS modules. Heat is rejected through the housing/radiator, which is similar in construction to the ASRG. Mass and power analysis for these systems indicate that specific

  18. Hybrid thermoelectric piezoelectric generator

    NASA Astrophysics Data System (ADS)

    Montgomery, D. S.; Hewitt, C. A.; Carroll, D. L.

    2016-06-01

    This work presents an integration of flexible thermoelectric and piezoelectric materials into a single device structure. This device architecture overcomes several prohibitive issues facing the combination of traditional thermoelectric and piezoelectric generators, while optimizing performance of the combined power output. The structure design uses a carbon nanotube/polymer thin film as a flexible thermoelectric generator that doubles as an electrode on a piezoelectric generator made of poly(vinylidene fluoride). An example 2 × 2 array of devices is shown to generate 89% of the maximum thermoelectric power, and provide 5.3 times more piezoelectric voltage when compared with a traditional device.

  19. Thermophotovoltaic energy generation

    DOEpatents

    Celanovic, Ivan; Chan, Walker; Bermel, Peter; Yeng, Adrian Y. X.; Marton, Christopher; Ghebrebrhan, Michael; Araghchini, Mohammad; Jensen, Klavs F.; Soljacic, Marin; Joannopoulos, John D.; Johnson, Steven G.; Pilawa-Podgurski, Robert; Fisher, Peter

    2015-08-25

    Inventive systems and methods for the generation of energy using thermophotovoltaic cells are described. Also described are systems and methods for selectively emitting electromagnetic radiation from an emitter for use in thermophotovoltaic energy generation systems. In at least some of the inventive energy generation systems and methods, a voltage applied to the thermophotovoltaic cell (e.g., to enhance the power produced by the cell) can be adjusted to enhance system performance. Certain embodiments of the systems and methods described herein can be used to generate energy relatively efficiently.

  20. Apollo - A pioneering generation

    NASA Technical Reports Server (NTRS)

    Fries, S. D.

    1986-01-01

    This paper describes an ongoing study of the National Aeronautics and Space Administration's (NASA's) first generation of engineers - the generation which accomplished the United States' first major achievements in manned space exploration. Combining statistical analysis with personal interviews, the study explores questions such as the origins, motivations, and career histories of NASA's first generation of engineers; that generation's role in NASA's current leadership; the relationships of science, engineering, and management in NASA's institutional culture; and changes experienced within NASA during and after the Apollo program.

  1. NEGATIVE GATE GENERATOR

    DOEpatents

    Jones, C.S.; Eaton, T.E.

    1958-02-01

    This patent relates to pulse generating circuits and more particularly to rectangular pulse generators. The pulse generator of the present invention incorporates thyratrons as switching elements to discharge a first capacitor through a load resistor to initiate and provide the body of a Pulse, and subsequently dlscharge a second capacitor to impress the potential of its charge, with opposite potential polarity across the load resistor to terminate the pulse. Accurate rectangular pulses in the millimicrosecond range are produced across a low impedance by this generator.

  2. STEAM GENERATOR GROUP PROJECT

    SciTech Connect

    Clark, R. A.; Lewis, M

    1985-09-01

    This report is a summary of progress in the Surry Steam Generator Group Project for 1984. Information is presented on the analysis of two baseline eddy current inspections of the generator. Round robin series of tests using standard in-service inspection techniques are described along with some preliminary results. Observations are reported of degradation found on tubing specimens removed from the generator, and on support plates characterized in-situ. Residual stresses measured on a tubing specimen are reported. Two steam generator repair demonstrations are described; one for antivibration bar replacement, and one on tube repair methods. Chemical analyses are shown for sludge samples removed from above the tube sheet.

  3. First-Generation Students: Identifying Barriers to Academic Persistence

    ERIC Educational Resources Information Center

    Godwin, Angela Felicia

    2012-01-01

    First-generation students are more likely than non-first-generation students to depart from a postsecondary institution before a degree is attained. Factors that could impact academic persistence among first-generation students include low self-efficacy, lack of financial resources and parental support, poor college planning, and minimal school…

  4. Modular Stirling Radioisotope Generator

    NASA Technical Reports Server (NTRS)

    Schmitz, Paul C.; Mason, Lee S.; Schifer, Nicholas A.

    2015-01-01

    High efficiency radioisotope power generators will play an important role in future NASA space exploration missions. Stirling Radioisotope Generators (SRG) have been identified as a candidate generator technology capable of providing mission designers with an efficient, high specific power electrical generator. SRGs high conversion efficiency has the potential to extend the limited Pu-238 supply when compared with current Radioisotope Thermoelectric Generators (RTG). Due to budgetary constraints, the Advanced Stirling Radioisotope Generator (ASRG) was canceled in the fall of 2013. Over the past year a joint study by NASA and DOE called the Nuclear Power Assessment Study (NPAS) recommended that Stirling technologies continue to be explored. During the mission studies of the NPAS, spare SRGs were sometimes required to meet mission power system reliability requirements. This led to an additional mass penalty and increased isotope consumption levied on certain SRG-based missions. In an attempt to remove the spare power system, a new generator architecture is considered which could increase the reliability of a Stirling generator and provide a more fault-tolerant power system. This new generator called the Modular Stirling Radioisotope Generator (MSRG) employs multiple parallel Stirling convertor/controller strings, all of which share the heat from the General Purpose Heat Source (GPHS) modules. For this design, generators utilizing one to eight GPHS modules were analyzed, which provide about 50 to 450 watts DC to the spacecraft, respectively. Four Stirling convertors are arranged around each GPHS module resulting in from 4 to 32 Stirling/controller strings. The convertors are balanced either individually or in pairs, and are radiatively coupled to the GPHS modules. Heat is rejected through the housing/radiator which is similar in construction to the ASRG. Mass and power analysis for these systems indicate that specific power may be slightly lower than the ASRG and

  5. Predictive Factors of Late Radiation Fibrosis: A Prospective Study in Non-Small Cell Lung Cancer

    SciTech Connect

    Mazeron, Renaud; Etienne-Mastroianni, Benedicte; Perol, David; Arpin, Dominique; Vincent, Michel; Falchero, Lionel; Martel-Lafay, Isabelle; Carrie, Christian; Claude, Line

    2010-05-01

    Purpose: To determine predictive factors of late radiation fibrosis (RF) after conformal radiotherapy (3D-RT) in non-small cell lung cancer (NSCLC). Methods and Materials: Ninety-six patients with Stage IA-IIIB NSCLC were included in a prospective trial. Clinical evaluation, chest X-ray, and pulmonary functional tests including diffusion parameters were performed before and 6 months after radiotherapy. An independent panel of experts prospectively analyzed RF, using Late Effects in Normal Tissues-Subjective, Objective, Management and Analytic scales classification. Logistic regression analysis was performed to identify relationships between clinical, functional, or treatment parameters and incidence of RF. Variations of circulating serum levels of pro-inflammatory (interleukin-6, tumor necrosis factor alpha, tumor growth factor beta1) and anti-inflammatory (interleukin-10) cytokines during 3D-RT were examined to identify correlations with RF. Results: Of the 96 patients included, 72 were evaluable for RF at 6 months. Thirty-seven (51.4%) developed RF (Grade >=1), including six severe RF (Grades 2-3; 8.3%). In univariate analysis, only poor Karnofsky Performance Status and previous acute radiation pneumonitis were associated with RF (p < 0.05). Dosimetric factors (mean lung dose, percentage of lung volume receiving more than 10, 20, 30, 40, and 50 Gy) were highly correlated with RF (p < 0.001). In multivariate analysis, previous acute radiation pneumonitis and dosimetric parameters were significantly correlated with RF occurrence. It was not significantly correlated either with cytokines at baseline or with their variation during 3D-RT. Conclusions: This study confirms the importance of dosimetric parameters to limit the risk of RF. Contrary to acute radiation pneumonitis, RF was not correlated to cytokine variations during 3D-RT.

  6. Arbitrary waveform generator

    NASA Astrophysics Data System (ADS)

    Blackmon, Fletcher A.

    1992-04-01

    It is a general purpose and object of the present invention to provide an arbitrary waveform generator. It is a further object that the generator has the ability to produce both pulse waveforms and continuous waveforms. Other objects are that the generator be compact and only require low power for lending itself to battery powered operation. These objects are accomplished with the present invention by providing a system in which digital waveforms are created using a software package such as DADiSP. The software package forms signals that are then transferred to an EPROM. Each signal type occupies a certain block of address space within the EPROM. A great number of signals may be digitally stored in this way. The operator then constructs simple microprocessor computer codes to access any signal, any combination of signals, or all signals to form a unique waveform generation sequence. Therefore the operator selects arbitrarily which of the previously stored signals to generate. Key features include the EPROM storing a single pulse for pulse waveforms and a single period of waveform for continuous waveforms. Other key features are the ability to control the sequence of generation, the number of times each signal is generated, the time between pulses, and the time between the generation of different signal types. These features are controlled by the microprocessor codes residing in a microprocessor.

  7. The fifth generation computer

    SciTech Connect

    Moto-Oka, T.; Kitsuregawa, M.

    1985-01-01

    The leader of Japan's Fifth Generation computer project, known as the 'Apollo' project, and a young computer scientist elucidate in this book the process of how the idea came about, international reactions, the basic technology, prospects for realization, and the abilities of the Fifth Generation computer. Topics considered included forecasting, research programs, planning, and technology impacts.

  8. Generation Y Perspectives

    NASA Technical Reports Server (NTRS)

    Skytland, Nicholas; Painting, Kristen; Barrera, Aaron; Fitzpatrick, Garret

    2008-01-01

    This viewgraph presentation reviews the perception of NASA and the importance of engaging those people born between 1977 and 2000, also known as Generation Y. It examines some of the differences in attitudes and experiences, and how it reflects on how they view NASA. It also discusses use of the internet in connecting to the people from that generation.

  9. Hospitality services generate revenue.

    PubMed

    Bizouati, S

    1993-01-01

    An increasing number of hospitals are undertaking external revenue-generating activities to supplement their shrinking budgets. Written at the request of Leadership, this article outlines an example of a successful catering service -- a money-generating business that more Canadian hospitals could profitably consider.

  10. Managing Generational Diversity

    ERIC Educational Resources Information Center

    O'Donovan, Eamonn

    2009-01-01

    Many school leaders have explored the issue of diversity when it comes to students, teachers and staff. Their focus typically has been on gender and ethnicity. However, generational diversity, an area of diversity that warrants serious consideration, has received less attention. Generational intelligence is important today for two reasons. First…

  11. The Next Great Generation?

    ERIC Educational Resources Information Center

    Brownstein, Andrew

    2000-01-01

    Discusses ideas from a new book, "Millennials Rising: The Next Great Generation," (by Neil Howe and William Strauss) suggesting that youth culture is on the cusp of a radical shift with the generation beginning with this year's college freshmen who are typically team oriented, optimistic, and poised for greatness on a global scale. Includes a…

  12. Geometric grid generation

    NASA Technical Reports Server (NTRS)

    Ives, David

    1995-01-01

    This paper presents a highly automated hexahedral grid generator based on extensive geometrical and solid modeling operations developed in response to a vision of a designer-driven one day turnaround CFD process which implies a designer-driven one hour grid generation process.

  13. Internal split field generator

    DOEpatents

    Thundat; ,Thomas George; Van Neste, Charles W.; Vass, Arpad Alexander

    2012-01-03

    A generator includes a coil of conductive material. A stationary magnetic field source applies a stationary magnetic field to the coil. An internal magnetic field source is disposed within a cavity of the coil to apply a moving magnetic field to the coil. The stationary magnetic field interacts with the moving magnetic field to generate an electrical energy in the coil.

  14. Cross-Generational Storytelling

    ERIC Educational Resources Information Center

    Smith, Cindy; Thurston, Judy Kay

    2007-01-01

    What happens when you combine senior citizens, pre-service art teachers, and elementary students? Cross-generational connections based on sharing memories, ideas, skills, laughter, tears, and creativity. The authors describe the cross-generational book exchange project. This project was initiated when a group of Central Michigan University (CMU)…

  15. Automatic finite element generators

    NASA Technical Reports Server (NTRS)

    Wang, P. S.

    1984-01-01

    The design and implementation of a software system for generating finite elements and related computations are described. Exact symbolic computational techniques are employed to derive strain-displacement matrices and element stiffness matrices. Methods for dealing with the excessive growth of symbolic expressions are discussed. Automatic FORTRAN code generation is described with emphasis on improving the efficiency of the resultant code.

  16. Generative Processes: Thick Drawing

    ERIC Educational Resources Information Center

    Wallick, Karl

    2012-01-01

    This article presents techniques and theories of generative drawing as a means for developing complex content in architecture design studios. Appending the word "generative" to drawing adds specificity to the most common representation tool and clarifies that such drawings are not singularly about communication or documentation but are also…

  17. Generativity and Flourishing

    ERIC Educational Resources Information Center

    Snow, Nancy

    2015-01-01

    The psychological construct of "generativity" was introduced by Erik Erikson in "Childhood and Society" in 1950. This rich and complex notion encompasses the constellation of desires, concerns and commitments that motivate individuals and societies to pass on legacies to future generations. "Flourishing," which means,…

  18. When Generations Collide

    ERIC Educational Resources Information Center

    Fogg, Piper

    2009-01-01

    As members of Generations X and Y face a workplace dominated by boomers, they are all starting to chafe. Some colleges are having trouble attracting, managing, and sometimes retaining people younger than 35. Members of the younger generations grew up watching their parents sacrifice for their careers, and they want something different: balance and…

  19. When Generations Collide

    ERIC Educational Resources Information Center

    Fogg, Piper

    2008-01-01

    When four generations converge in the academic workplace, it can create serious culture clashes. It is happening across college campuses--in offices as diverse as admissions, student affairs, legal affairs, and technology. It is especially striking in the faculty ranks, where generational challenges have extra significance amid recruiting efforts,…

  20. Improved solid aerosol generator

    DOEpatents

    Prescott, D.S.; Schober, R.K.; Beller, J.

    1988-07-19

    An improved solid aerosol generator used to produce a gas borne stream of dry, solid particles of predetermined size and concentration. The improved solid aerosol generator nebulizes a feed solution of known concentration with a flow of preheated gas and dries the resultant wet heated aerosol in a grounded, conical heating chamber, achieving high recovery and flow rates. 2 figs.

  1. Solid aerosol generator

    DOEpatents

    Prescott, Donald S.; Schober, Robert K.; Beller, John

    1992-01-01

    An improved solid aerosol generator used to produce a gas borne stream of dry, solid particles of predetermined size and concentration. The improved solid aerosol generator nebulizes a feed solution of known concentration with a flow of preheated gas and dries the resultant wet heated aerosol in a grounded, conical heating chamber, achieving high recovery and flow rates.

  2. Solid aerosol generator

    DOEpatents

    Prescott, D.S.; Schober, R.K.; Beller, J.

    1992-03-17

    An improved solid aerosol generator used to produce a gas borne stream of dry, solid particles of predetermined size and concentration is disclosed. The improved solid aerosol generator nebulizes a feed solution of known concentration with a flow of preheated gas and dries the resultant wet heated aerosol in a grounded, conical heating chamber, achieving high recovery and flow rates. 2 figs.

  3. Hospitality services generate revenue.

    PubMed

    Bizouati, S

    1993-01-01

    An increasing number of hospitals are undertaking external revenue-generating activities to supplement their shrinking budgets. Written at the request of Leadership, this article outlines an example of a successful catering service -- a money-generating business that more Canadian hospitals could profitably consider. PMID:10127850

  4. Next generation space robot

    NASA Technical Reports Server (NTRS)

    Iwata, Tsutomu; Oda, Mitsushige; Imai, Ryoichi

    1989-01-01

    The recent research effort on the next generation space robots is presented. The goals of this research are to develop the fundamental technologies and to acquire the design parameters of the next generation space robot. Visual sensing and perception, dexterous manipulation, man machine interface and artificial intelligence techniques such as task planning are identified as the key technologies.

  5. Generation of monoclonal antibodies to recombinant vascular endothelial growth factor.

    PubMed

    Shein, S A; Gurina, O I; Leopol'd, A V; Baklaushev, V P; Korchagina, A A; Grinenko, N F; Ivanova, N V; Volgina, N E; Ryabukhin, I A; Chekhonin, V P

    2012-05-01

    Female BALB/c mice were subcutaneously immunized with recombinant VEGF-164. After 3 immunization cycles, splenic B cells from immunized mouse were fused with immortalized myeloma culture SP2/0-Ag14 cells. Screening of hybrid cells producing anti-VEGF antibodies was performed by ELISA and immunocytochemical analysis on cultured C6 glioma cells. Subsequent cloning yielded hybridoma stably expressing monoclonal anti-VEGF antibodies recognizing recombinant and native VEGF. PMID:22808513

  6. Fastrac Gas Generator Testing

    NASA Technical Reports Server (NTRS)

    Nesman, Tomas E.; Dennis, Jay

    2001-01-01

    A rocket engine gas generator component development test was recently conducted at the Marshall Space Flight Center. This gas generator is intended to power a rocket engine turbopump by the combustion of Lox and RP-1. The testing demonstrated design requirements for start sequence, wall compatibility, performance, and stable combustion. During testing the gas generator injector was modified to improve distribution of outer wall coolant and the igniter boss was modified to investigate the use of a pyrotechnic igniter. Expected chamber pressure oscillations at longitudinal acoustic mode were measured for three different chamber lengths tested. High amplitude discrete oscillations resulted in the chamber-alone configurations when chamber acoustic modes coupled with feed-system acoustics modes. For the full gas generator configuration, which included a turbine inlet manifold, high amplitude oscillations occurred only at off-design very low power levels. This testing led to a successful gas generator design for the Fastrac 60,000 lb thrust engine.

  7. Fastrac Gas Generator Testing

    NASA Technical Reports Server (NTRS)

    Nesman, Tomas E.; Dennis, Jay

    1999-01-01

    A rocket engine gas generator component development test was recently conducted at the Marshall Space Flight Center. This gas generator was intended to power a rocket engine turbopump by the combustion of Lox and RP-1. The testing demonstrated design requirements for start sequence, wall compatibility, performance, and stable combustion. During testing the gas generator injector was modified to improve distribution of outer wall coolant and the igniter boss was modified to investigate the use of a pyrotechnic igniter, Expected chamber pressure oscillations at longitudinal acoustic modes were measured for three different chamber lengths tested. High amplitude discrete oscillations occurred in the chamber-alone configurations when chamber acoustic modes coupled with feed-system acoustics modes. For the full gas generator configuration, which included the turbine inlet manifold simulator, high amplitude oscillations occurred only at off-design very low power levels. This testing led to a successful gas generator design for the Fastrac 60,000 lb thrust engine.

  8. Digital relief generation from 3D models

    NASA Astrophysics Data System (ADS)

    Wang, Meili; Sun, Yu; Zhang, Hongming; Qian, Kun; Chang, Jian; He, Dongjian

    2016-09-01

    It is difficult to extend image-based relief generation to high-relief generation, as the images contain insufficient height information. To generate reliefs from three-dimensional (3D) models, it is necessary to extract the height fields from the model, but this can only generate bas-reliefs. To overcome this problem, an efficient method is proposed to generate bas-reliefs and high-reliefs directly from 3D meshes. To produce relief features that are visually appropriate, the 3D meshes are first scaled. 3D unsharp masking is used to enhance the visual features in the 3D mesh, and average smoothing and Laplacian smoothing are implemented to achieve better smoothing results. A nonlinear variable scaling scheme is then employed to generate the final bas-reliefs and high-reliefs. Using the proposed method, relief models can be generated from arbitrary viewing positions with different gestures and combinations of multiple 3D models. The generated relief models can be printed by 3D printers. The proposed method provides a means of generating both high-reliefs and bas-reliefs in an efficient and effective way under the appropriate scaling factors.

  9. Next-generation Digital Earth

    PubMed Central

    Goodchild, Michael F.; Guo, Huadong; Annoni, Alessandro; Bian, Ling; de Bie, Kees; Campbell, Frederick; Craglia, Max; Ehlers, Manfred; van Genderen, John; Jackson, Davina; Lewis, Anthony J.; Pesaresi, Martino; Remetey-Fülöpp, Gábor; Simpson, Richard; Skidmore, Andrew; Wang, Changlin; Woodgate, Peter

    2012-01-01

    A speech of then-Vice President Al Gore in 1998 created a vision for a Digital Earth, and played a role in stimulating the development of a first generation of virtual globes, typified by Google Earth, that achieved many but not all the elements of this vision. The technical achievements of Google Earth, and the functionality of this first generation of virtual globes, are reviewed against the Gore vision. Meanwhile, developments in technology continue, the era of “big data” has arrived, the general public is more and more engaged with technology through citizen science and crowd-sourcing, and advances have been made in our scientific understanding of the Earth system. However, although Google Earth stimulated progress in communicating the results of science, there continue to be substantial barriers in the public’s access to science. All these factors prompt a reexamination of the initial vision of Digital Earth, and a discussion of the major elements that should be part of a next generation. PMID:22723346

  10. Next-generation Digital Earth.

    PubMed

    Goodchild, Michael F; Guo, Huadong; Annoni, Alessandro; Bian, Ling; de Bie, Kees; Campbell, Frederick; Craglia, Max; Ehlers, Manfred; van Genderen, John; Jackson, Davina; Lewis, Anthony J; Pesaresi, Martino; Remetey-Fülöpp, Gábor; Simpson, Richard; Skidmore, Andrew; Wang, Changlin; Woodgate, Peter

    2012-07-10

    A speech of then-Vice President Al Gore in 1998 created a vision for a Digital Earth, and played a role in stimulating the development of a first generation of virtual globes, typified by Google Earth, that achieved many but not all the elements of this vision. The technical achievements of Google Earth, and the functionality of this first generation of virtual globes, are reviewed against the Gore vision. Meanwhile, developments in technology continue, the era of "big data" has arrived, the general public is more and more engaged with technology through citizen science and crowd-sourcing, and advances have been made in our scientific understanding of the Earth system. However, although Google Earth stimulated progress in communicating the results of science, there continue to be substantial barriers in the public's access to science. All these factors prompt a reexamination of the initial vision of Digital Earth, and a discussion of the major elements that should be part of a next generation.

  11. Coiled transmission line pulse generators

    DOEpatents

    McDonald, Kenneth Fox

    2010-11-09

    Methods and apparatus are provided for fabricating and constructing solid dielectric "Coiled Transmission Line" pulse generators in radial or axial coiled geometries. The pour and cure fabrication process enables a wide variety of geometries and form factors. The volume between the conductors is filled with liquid blends of monomers, polymers, oligomers, and/or cross-linkers and dielectric powders; and then cured to form high field strength and high dielectric constant solid dielectric transmission lines that intrinsically produce ideal rectangular high voltage pulses when charged and switched into matched impedance loads. Voltage levels may be increased by Marx and/or Blumlein principles incorporating spark gap or, preferentially, solid state switches (such as optically triggered thyristors) which produce reliable, high repetition rate operation. Moreover, these Marxed pulse generators can be DC charged and do not require additional pulse forming circuitry, pulse forming lines, transformers, or an a high voltage spark gap output switch. The apparatus accommodates a wide range of voltages, impedances, pulse durations, pulse repetition rates, and duty cycles. The resulting mobile or flight platform friendly cylindrical geometric configuration is much more compact, light-weight, and robust than conventional linear geometries, or pulse generators constructed from conventional components. Installing additional circuitry may accommodate optional pulse shape improvements. The Coiled Transmission Lines can also be connected in parallel to decrease the impedance, or in series to increase the pulse length.

  12. Wind power generating system

    SciTech Connect

    Schachle, Ch.; Schachle, E. C.; Schachle, J. R.; Schachle, P. J.

    1985-03-12

    Normally feathered propeller blades of a wind power generating system unfeather in response to the actuation of a power cylinder that responds to actuating signals. Once operational, the propellers generate power over a large range of wind velocities. A maximum power generation design point signals a feather response of the propellers so that once the design point is reached no increase in power results, but the system still generates power. At wind speeds below this maximum point, propeller speed and power output optimize to preset values. The propellers drive a positive displacement pump that in turn drives a positive displacement motor of the swash plate type. The displacement of the motor varies depending on the load on the system, with increasing displacement resulting in increasing propeller speeds, and the converse. In the event of dangerous but not clandestine problems developing in the system, a control circuit dumps hydraulic pressure from the unfeathering cylinder resulting in a predetermined, lower operating pressure produced by the pump. In the event that a problem of potentially cladestine consequence arises, the propeller unfeathering cylinder immediately unloads. Upon startup, a bypass around the motor is blocked, applying a pressure across the motor. The motor drives the generator until the generator reaches a predetermined speed whereupon the generator is placed in circuit with a utility grid and permitted to motor up to synchronous speed.

  13. Higher harmonic generation microscopy.

    PubMed

    Sun, Chi-Kuang

    2005-01-01

    Higher harmonic-generation, including second harmonic generation and third harmonic generation, leaves no energy deposition to the interacted matters due to its virtual-level transition characteristic, providing a truly non-invasive modality and is ideal for in vivo imaging of live specimens without any preparation. Second harmonic generation microscopy provides images on stacked membranes and arranged proteins with organized nano-structures due to the bio-photonic crystalline effect. Third harmonic generation microscopy provides general cellular or subcellular interface imaging due to optical inhomogeneity. Due to their virtual-transition nature, no saturation or bleaching in the generated signal is expected. With no energy release, continuous viewing without compromising sample viability can thus be achieved. Combined with its nonlinearity, higher harmonic generation microscopy provides sub-micron three-dimensional sectioning capability and millimeter penetration in live samples without using fluorescence and exogenous markers, offering morphological, structural, functional, and cellular information of biomedical specimens without modifying their natural biological and optical environments.

  14. Spin hydrodynamic generation

    NASA Astrophysics Data System (ADS)

    Takahashi, R.; Matsuo, M.; Ono, M.; Harii, K.; Chudo, H.; Okayasu, S.; Ieda, J.; Takahashi, S.; Maekawa, S.; Saitoh, E.

    2016-01-01

    Magnetohydrodynamic generation is the conversion of fluid kinetic energy into electricity. Such conversion, which has been applied to various types of electric power generation, is driven by the Lorentz force acting on charged particles and thus a magnetic field is necessary. On the other hand, recent studies of spintronics have revealed the similarity between the function of a magnetic field and that of spin-orbit interactions in condensed matter. This suggests the existence of an undiscovered route to realize the conversion of fluid dynamics into electricity without using magnetic fields. Here we show electric voltage generation from fluid dynamics free from magnetic fields; we excited liquid-metal flows in a narrow channel and observed longitudinal voltage generation in the liquid. This voltage has nothing to do with electrification or thermoelectric effects, but turned out to follow a universal scaling rule based on a spin-mediated scenario. The result shows that the observed voltage is caused by spin-current generation from a fluid motion: spin hydrodynamic generation. The observed phenomenon allows us to make mechanical spin-current and electric generators, opening a door to fluid spintronics.

  15. Compact neutron generator

    DOEpatents

    Leung, Ka-Ngo; Lou, Tak Pui

    2005-03-22

    A compact neutron generator has at its outer circumference a toroidal shaped plasma chamber in which a tritium (or other) plasma is generated. A RF antenna is wrapped around the plasma chamber. A plurality of tritium ion beamlets are extracted through spaced extraction apertures of a plasma electrode on the inner surface of the toroidal plasma chamber and directed inwardly toward the center of neutron generator. The beamlets pass through spaced acceleration and focusing electrodes to a neutron generating target at the center of neutron generator. The target is typically made of titanium tubing. Water is flowed through the tubing for cooling. The beam can be pulsed rapidly to achieve ultrashort neutron bursts. The target may be moved rapidly up and down so that the average power deposited on the surface of the target may be kept at a reasonable level. The neutron generator can produce fast neutrons from a T-T reaction which can be used for luggage and cargo interrogation applications. A luggage or cargo inspection system has a pulsed T-T neutron generator or source at the center, surrounded by associated gamma detectors and other components for identifying explosives or other contraband.

  16. OMG: Open Molecule Generator

    PubMed Central

    2012-01-01

    Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG), which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck. PMID:22985496

  17. OMG: Open Molecule Generator.

    PubMed

    Peironcely, Julio E; Rojas-Chertó, Miguel; Fichera, Davide; Reijmers, Theo; Coulier, Leon; Faulon, Jean-Loup; Hankemeier, Thomas

    2012-01-01

    Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG), which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck. PMID:22985496

  18. OMG: Open Molecule Generator.

    PubMed

    Peironcely, Julio E; Rojas-Chertó, Miguel; Fichera, Davide; Reijmers, Theo; Coulier, Leon; Faulon, Jean-Loup; Hankemeier, Thomas

    2012-09-17

    Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG), which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck.

  19. Growth factors

    SciTech Connect

    Golde, D.W.; Herschman, H.R.; Lusis, A.J.; Groopman, J.E.

    1980-05-01

    Humoral regulation of somatic and hematopoietic cell growth has been intensely investigated during the past decade. Growth hormone is unique because it regulates the size of the person within the constraints of the genetic program. The somatomedins and insulin growth factors are low molecular weight polypeptides believed to mediate some functions of growth hormone. Epithelial growth factor and nerve growth factor are well-characterized polypeptides that influence the growth and differentiation of epithelial and neural tissues and interact with specific cell surface receptors. The hematopoietins are a family of polypeptide hormones that specifically regulate the proliferation and differentiation of stem cells giving rise to erythrocytes, granulocytes, monocytes, megakaryocytes, and B and T lymphocytes. Platelet-derived growth factor modulates the proliferation of fibroblasts in vitro and may have a role in the development of atherosclerosis and myelofibrosis. New knowledge on the biochemistry and physiology of growth factors will probably have a substantial impact on our understanding of human diseases involving abnormal cell growth.

  20. Graph Generator Survey

    SciTech Connect

    Lothian, Josh; Powers, Sarah S; Sullivan, Blair D; Baker, Matthew B; Schrock, Jonathan; Poole, Stephen W

    2013-12-01

    The benchmarking effort within the Extreme Scale Systems Center at Oak Ridge National Laboratory seeks to provide High Performance Computing benchmarks and test suites of interest to the DoD sponsor. The work described in this report is a part of the effort focusing on graph generation. A previously developed benchmark, SystemBurn, allowed the emulation of dierent application behavior profiles within a single framework. To complement this effort, similar capabilities are desired for graph-centric problems. This report examines existing synthetic graph generator implementations in preparation for further study on the properties of their generated synthetic graphs.

  1. PULSE SYNTHESIZING GENERATOR

    DOEpatents

    Kerns, Q.A.

    1963-08-01

    >An electronlc circuit for synthesizing electrical current pulses having very fast rise times includes several sinewave generators tuned to progressively higher harmonic frequencies with signal amplitudes and phases selectable according to the Fourier series of the waveform that is to be synthesized. Phase control is provided by periodically triggering the generators at precisely controlled times. The outputs of the generators are combined in a coaxial transmission line. Any frequency-dependent delays that occur in the transmission line can be readily compensated for so that the desired signal wave shape is obtained at the output of the line. (AEC)

  2. Owl: electronic datasheet generator.

    PubMed

    Appleton, Evan; Tao, Jenhan; Wheatley, F Carter; Desai, Devina H; Lozanoski, Thomas M; Shah, Pooja D; Awtry, Jake A; Jin, Shawn S; Haddock, Traci L; Densmore, Douglas M

    2014-12-19

    Owl ( www.owlcad.org ) is a biodesign automation tool that generates electronic datasheets for synthetic biological parts using common formatting. Data can be retrieved automatically from existing repositories and modified in the Owl user interface (UI). Owl uses the data to generate an HTML page with standard typesetting that can be saved as a PDF file. Here we present the Owl software tool in its alpha version, its current UI, its description of input data for generating a datasheet, its example datasheets, and the vision of the tool's role in biodesign automation.

  3. Synthetic guide star generation

    DOEpatents

    Payne, Stephen A.; Page, Ralph H.; Ebbers, Christopher A.; Beach, Raymond J.

    2004-03-09

    A system for assisting in observing a celestial object and providing synthetic guide star generation. A lasing system provides radiation at a frequency at or near 938 nm and radiation at a frequency at or near 1583 nm. The lasing system includes a fiber laser operating between 880 nm and 960 nm and a fiber laser operating between 1524 nm and 1650 nm. A frequency-conversion system mixes the radiation and generates light at a frequency at or near 589 nm. A system directs the light at a frequency at or near 589 nm toward the celestial object and provides synthetic guide star generation.

  4. Synthetic guide star generation

    DOEpatents

    Payne, Stephen A [Castro Valley, CA; Page, Ralph H [Castro Valley, CA; Ebbers, Christopher A [Livermore, CA; Beach, Raymond J [Livermore, CA

    2008-06-10

    A system for assisting in observing a celestial object and providing synthetic guide star generation. A lasing system provides radiation at a frequency at or near 938 nm and radiation at a frequency at or near 1583 nm. The lasing system includes a fiber laser operating between 880 nm and 960 nm and a fiber laser operating between 1524 nm and 1650 nm. A frequency-conversion system mixes the radiation and generates light at a frequency at or near 589 nm. A system directs the light at a frequency at or near 589 nm toward the celestial object and provides synthetic guide star generation.

  5. Cryogenic generator cooling

    NASA Astrophysics Data System (ADS)

    Eckels, P. W.; Fagan, T. J.; Parker, J. H., Jr.; Long, L. J.; Shestak, E. J.; Calfo, R. M.; Hannon, W. F.; Brown, D. B.; Barkell, J. W.; Patterson, A.

    The concept for a hydrogen cooled aluminum cryogenic generator was presented by Schlicher and Oberly in 1985. Following their lead, this paper describes the thermal design of a high voltage dc, multimegawatt generator of high power density. The rotor and stator are cooled by saturated liquid and supercritical hydrogen, respectively. The brushless exciter on the same shaft is also cooled by liquid hydrogen. Component development testing is well under way and some of the test results concerning the thermohydraulic performance of the conductors are reported. The aluminum cryogenic generator's characteristics are attractive for hydrogen economy applications.

  6. Automated knowledge generation

    NASA Technical Reports Server (NTRS)

    Myler, Harley R.; Gonzalez, Avelino J.

    1988-01-01

    The general objectives of the NASA/UCF Automated Knowledge Generation Project were the development of an intelligent software system that could access CAD design data bases, interpret them, and generate a diagnostic knowledge base in the form of a system model. The initial area of concentration is in the diagnosis of the process control system using the Knowledge-based Autonomous Test Engineer (KATE) diagnostic system. A secondary objective was the study of general problems of automated knowledge generation. A prototype was developed, based on object-oriented language (Flavors).

  7. Solid expellant plasma generator

    NASA Technical Reports Server (NTRS)

    Stone, Nobie H. (Inventor); Poe, Garrett D. (Inventor); Rood, Robert (Inventor)

    2010-01-01

    An improved solid expellant plasma generator has been developed. The plasma generator includes a support housing, an electrode rod located in the central portion of the housing, and a mass of solid expellant material that surrounds the electrode rod within the support housing. The electrode rod and the solid expellant material are made of separate materials that are selected so that the electrode and the solid expellant material decompose at the same rate when the plasma generator is ignited. This maintains a point of discharge of the plasma at the interface between the electrode and the solid expellant material.

  8. Reliability model generator

    NASA Technical Reports Server (NTRS)

    McMann, Catherine M. (Inventor); Cohen, Gerald C. (Inventor)

    1991-01-01

    An improved method and system for automatically generating reliability models for use with a reliability evaluation tool is described. The reliability model generator of the present invention includes means for storing a plurality of low level reliability models which represent the reliability characteristics for low level system components. In addition, the present invention includes means for defining the interconnection of the low level reliability models via a system architecture description. In accordance with the principles of the present invention, a reliability model for the entire system is automatically generated by aggregating the low level reliability models based on the system architecture description.

  9. Magnetohydrodynamic power generation

    NASA Technical Reports Server (NTRS)

    Smith, J. L.

    1984-01-01

    Magnetohydrodynamic (MHD) Power Generation is a concise summary of MHD theory, history, and future trends. Results of the major international MHD research projects are discussed. Data from MHD research is included. Economics of initial and operating costs are considered.

  10. Vector generator scan converter

    DOEpatents

    Moore, J.M.; Leighton, J.F.

    1988-02-05

    High printing speeds for graphics data are achieved with a laser printer by transmitting compressed graphics data from a main processor over an I/O channel to a vector generator scan converter which reconstructs a full graphics image for input to the laser printer through a raster data input port. The vector generator scan converter includes a microprocessor with associated microcode memory containing a microcode instruction set, a working memory for storing compressed data, vector generator hardware for drawing a full graphic image from vector parameters calculated by the microprocessor, image buffer memory for storing the reconstructed graphics image and an output scanner for reading the graphics image data and inputting the data to the printer. The vector generator scan converter eliminates the bottleneck created by the I/O channel for transmitting graphics data from the main processor to the laser printer, and increases printer speed up to thirty fold. 7 figs.

  11. Vector generator scan converter

    DOEpatents

    Moore, James M.; Leighton, James F.

    1990-01-01

    High printing speeds for graphics data are achieved with a laser printer by transmitting compressed graphics data from a main processor over an I/O (input/output) channel to a vector generator scan converter which reconstructs a full graphics image for input to the laser printer through a raster data input port. The vector generator scan converter includes a microprocessor with associated microcode memory containing a microcode instruction set, a working memory for storing compressed data, vector generator hardward for drawing a full graphic image from vector parameters calculated by the microprocessor, image buffer memory for storing the reconstructed graphics image and an output scanner for reading the graphics image data and inputting the data to the printer. The vector generator scan converter eliminates the bottleneck created by the I/O channel for transmitting graphics data from the main processor to the laser printer, and increases printer speed up to thirty fold.

  12. Biomass for Electricity Generation

    EIA Publications

    2002-01-01

    This paper examines issues affecting the uses of biomass for electricity generation. The methodology used in the National Energy Modeling System to account for various types of biomass is discussed, and the underlying assumptions are explained.

  13. Scram signal generator

    DOEpatents

    Johanson, Edward W.; Simms, Richard

    1981-01-01

    A scram signal generating circuit for nuclear reactor installations monitors a flow signal representing the flow rate of the liquid sodium coolant which is circulated through the reactor, and initiates reactor shutdown for a rapid variation in the flow signal, indicative of fuel motion. The scram signal generating circuit includes a long-term drift compensation circuit which processes the flow signal and generates an output signal representing the flow rate of the coolant. The output signal remains substantially unchanged for small variations in the flow signal, attributable to long term drift in the flow rate, but a rapid change in the flow signal, indicative of a fast flow variation, causes a corresponding change in the output signal. A comparator circuit compares the output signal with a reference signal, representing a given percentage of the steady state flow rate of the coolant, and generates a scram signal to initiate reactor shutdown when the output signal equals the reference signal.

  14. Local entropy generation analysis

    SciTech Connect

    Drost, M.K.; White, M.D.

    1991-02-01

    Second law analysis techniques have been widely used to evaluate the sources of irreversibility in components and systems of components but the evaluation of local sources of irreversibility in thermal processes has received little attention. While analytical procedures for evaluating local entropy generation have been developed, applications have been limited to fluid flows with analytical solutions for the velocity and temperature fields. The analysis of local entropy generation can be used to evaluate more complicated flows by including entropy generation calculations in a computational fluid dynamics (CFD) code. The research documented in this report consists of incorporating local entropy generation calculations in an existing CFD code and then using the code to evaluate the distribution of thermodynamic losses in two applications: an impinging jet and a magnetic heat pump. 22 refs., 13 figs., 9 tabs.

  15. Financing Distributed Generation

    SciTech Connect

    Walker, A.

    2001-06-29

    This paper introduces the engineer who is undertaking distributed generation projects to a wide range of financing options. Distributed generation systems (such as internal combustion engines, small gas turbines, fuel cells and photovoltaics) all require an initial investment, which is recovered over time through revenues or savings. An understanding of the cost of capital and financing structures helps the engineer develop realistic expectations and not be offended by the common requirements of financing organizations. This paper discusses several mechanisms for financing distributed generation projects: appropriations; debt (commercial bank loan); mortgage; home equity loan; limited partnership; vendor financing; general obligation bond; revenue bond; lease; Energy Savings Performance Contract; utility programs; chauffage (end-use purchase); and grants. The paper also discusses financial strategies for businesses focusing on distributed generation: venture capital; informal investors (''business angels''); bank and debt financing; and the stock market.

  16. Next Generation Internet Overview

    NASA Technical Reports Server (NTRS)

    desJardins, R.

    1998-01-01

    Various issues associated with next generation Internet are presented in viewgraph form. Specific topics include: 1) Internet architecture; 2) NASA's advanced networking; 3) Internet capability, capacity and applications; and 4) Systems engineering.

  17. Scram signal generator

    DOEpatents

    Johanson, E.W.; Simms, R.

    A scram signal generating circuit for nuclear reactor installations monitors a flow signal representing the flow rate of the liquid sodium coolant which is circulated through the reactor, and initiates reactor shutdown for a rapid variation in the flow signal, indicative of fuel motion. The scram signal generating circuit includes a long-term drift compensation circuit which processes the flow signal and generates an output signal representing the flow rate of the coolant. The output signal remains substantially unchanged for small variations in the flow signal, attributable to long term drift in the flow rate, but a rapid change in the flow signal, indicative of a fast flow variation, causes a corresponding change in the output signal. A comparator circuit compares the output signal with a reference signal, representing a given percentage of the steady state flow rate of the coolant, and generates a scram signal to initiate reactor shutdown when the output signal equals the reference signal.

  18. Relativistic electron beam generator

    DOEpatents

    Mooney, L.J.; Hyatt, H.M.

    1975-11-11

    A relativistic electron beam generator for laser media excitation is described. The device employs a diode type relativistic electron beam source having a cathode shape which provides a rectangular output beam with uniform current density.

  19. Vector generator scan converter

    SciTech Connect

    Moore, J.M.; Leighton, J.F.

    1990-04-17

    This patent describes high printing speeds for graphics data that are achieved with a laser printer by transmitting compressed graphics data from a main processor over an I/O (input/output) channel to a vector generator scan converter which reconstructs a full graphics image for input to the laser printer through a raster data input port. The vector generator scan converter includes a microprocessor with associated microcode memory containing a microcode instruction set, a working memory for storing compressed data, vector generator hardware for drawing a full graphic image from vector parameters calculated by the microprocessor, image buffer memory for storing the reconstructed graphics image and an output scanner for reading the graphics image data and inputting the data to the printer. The vector generator scan converter eliminates the bottleneck created by the I/O channel for transmitting graphics data from the main processor to the laser printer, and increases printer speed up to thirty fold.

  20. Oscillating fluid power generator

    SciTech Connect

    Morris, David C

    2014-02-25

    A system and method for harvesting the kinetic energy of a fluid flow for power generation with a vertically oriented, aerodynamic wing structure comprising one or more airfoil elements pivotably attached to a mast. When activated by the moving fluid stream, the wing structure oscillates back and forth, generating lift first in one direction then in the opposite direction. This oscillating movement is converted to unidirectional rotational movement in order to provide motive power to an electricity generator. Unlike other oscillating devices, this device is designed to harvest the maximum aerodynamic lift forces available for a given oscillation cycle. Because the system is not subjected to the same intense forces and stresses as turbine systems, it can be constructed less expensively, reducing the cost of electricity generation. The system can be grouped in more compact clusters, be less evident in the landscape, and present reduced risk to avian species.

  1. Surface-Enhanced Second-Harmonic Generation

    SciTech Connect

    Chen, C. K.; de Castro, A. R.B.; Shen, Y. R.

    1981-01-12

    Second harmonic generation at a silver-air interface was enhanced due to surface roughness by a factor of 10⁴. The local field enhancement is believed to be responsible for the effect. An unusually broad luminescence background extending far beyond the antiStokes side of the second harmonic was also observed.

  2. Wind electric generator project

    NASA Astrophysics Data System (ADS)

    1983-09-01

    A wind generator was installed and connected at Iowa Western Community College. It is heating water through four hot water tanks and proved to be an excellent demonstration project for the community. The college gets frequent inquiries about the windmill and has been very cooperative in informing the public about the success. The windmill generates more electricity than is needed to heat four hot water heaters and future plans are to hook up more. The project requires very little maintenance.

  3. Interactive DIF Generator

    NASA Technical Reports Server (NTRS)

    Preheim, Larry E.; Amy, Laraine; Young, Jimmie D.

    1993-01-01

    Interactive DIF Generator (IDG) computer program serves as utility to generate and manipulate directory interchange format (DIF) files. Creates and updates DIF files, sent to NASA's Master Directory, also referred to as International Global Change Directory at Goddard Space Flight Center. Many government and university data systems use Master Directory to advertise availability of research data. IDG is interactive software tool and requires mouse or trackball to operate. Written in C language.

  4. Liquid propellant gas generators

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The design of gas generators intended to provide hot gases for turbine drive is discussed. Emphasis is placed on the design and operation of bipropellant gas generators because of their wider use. Problems and limitations involved in turbine operation due to temperature effects are analyzed. Methods of temperature control of gas turbines and combustion products are examined. Drawings of critical sections of gas turbines to show their operation and areas of stress are included.

  5. Compact Mesh Generator

    2007-02-02

    The CMG is a small, lightweight, structured mesh generation code. It features a simple text input parser that allows setup of various meshes via a small set of text commands. Mesh generation data can be output to text, the silo file format, or the API can be directly queried by applications. It can run serially or in parallel via MPI. The CMG includes the ability to specify varius initial conditions on a mesh via meshmore » tags.« less

  6. Meshes: The next generation

    SciTech Connect

    Christon, M.; Hardin, D.; Compton, J.; Zosel, M.

    1994-08-29

    Building complex meshes for large-scale numerical simulations presents immense difficulties in exploiting high-performance computers. Industry and research leaders will describe the current state of the art for generating meshes for such large scientific problems. This will be followed by a panel and general audience discussion of the algorithmic and architectural issues surrounding the generation of meshes with10{sup 7} to 10{sup 9} grid points. (Note: The terms ``mesh`` and ``grid`` are used interchangeably in the literature.)

  7. Wind turbine generator system

    SciTech Connect

    Kirschbaum, H.S.

    1982-11-02

    Wind turbine generator systems incorporating a multi-speed pole amplitude modulated type dynamo electric machine allow efficient operation at consecutive speeds in a ratio preferably less than 2:1. A current limiting reactor, preferably including an inductance coil, and an over-running clutch, are utilized in conjunction with any multi-speed generation system to alleviate impact on a utility grid during switching among operational speeds.

  8. ADJUSTABLE DOUBLE PULSE GENERATOR

    DOEpatents

    Gratian, J.W.; Gratian, A.C.

    1961-08-01

    >A modulator pulse source having adjustable pulse width and adjustable pulse spacing is described. The generator consists of a cross coupled multivibrator having adjustable time constant circuitry in each leg, an adjustable differentiating circuit in the output of each leg, a mixing and rectifying circuit for combining the differentiated pulses and generating in its output a resultant sequence of negative pulses, and a final amplifying circuit for inverting and square-topping the pulses. (AEC)

  9. Next generation initiation techniques

    NASA Technical Reports Server (NTRS)

    Warner, Tom; Derber, John; Zupanski, Milija; Cohn, Steve; Verlinde, Hans

    1993-01-01

    Four-dimensional data assimilation strategies can generally be classified as either current or next generation, depending upon whether they are used operationally or not. Current-generation data-assimilation techniques are those that are presently used routinely in operational-forecasting or research applications. They can be classified into the following categories: intermittent assimilation, Newtonian relaxation, and physical initialization. It should be noted that these techniques are the subject of continued research, and their improvement will parallel the development of next generation techniques described by the other speakers. Next generation assimilation techniques are those that are under development but are not yet used operationally. Most of these procedures are derived from control theory or variational methods and primarily represent continuous assimilation approaches, in which the data and model dynamics are 'fitted' to each other in an optimal way. Another 'next generation' category is the initialization of convective-scale models. Intermittent assimilation systems use an objective analysis to combine all observations within a time window that is centered on the analysis time. Continuous first-generation assimilation systems are usually based on the Newtonian-relaxation or 'nudging' techniques. Physical initialization procedures generally involve the use of standard or nonstandard data to force some physical process in the model during an assimilation period. Under the topic of next-generation assimilation techniques, variational approaches are currently being actively developed. Variational approaches seek to minimize a cost or penalty function which measures a model's fit to observations, background fields and other imposed constraints. Alternatively, the Kalman filter technique, which is also under investigation as a data assimilation procedure for numerical weather prediction, can yield acceptable initial conditions for mesoscale models. The

  10. Steam generator tube failures

    SciTech Connect

    MacDonald, P.E.; Shah, V.N.; Ward, L.W.; Ellison, P.G.

    1996-04-01

    A review and summary of the available information on steam generator tubing failures and the impact of these failures on plant safety is presented. The following topics are covered: pressurized water reactor (PWR), Canadian deuterium uranium (CANDU) reactor, and Russian water moderated, water cooled energy reactor (VVER) steam generator degradation, PWR steam generator tube ruptures, the thermal-hydraulic response of a PWR plant with a faulted steam generator, the risk significance of steam generator tube rupture accidents, tubing inspection requirements and fitness-for-service criteria in various countries, and defect detection reliability and sizing accuracy. A significant number of steam generator tubes are defective and are removed from service or repaired each year. This wide spread damage has been caused by many diverse degradation mechanisms, some of which are difficult to detect and predict. In addition, spontaneous tube ruptures have occurred at the rate of about one every 2 years over the last 20 years, and incipient tube ruptures (tube failures usually identified with leak detection monitors just before rupture) have been occurring at the rate of about one per year. These ruptures have caused complex plant transients which have not always been easy for the reactor operators to control. Our analysis shows that if more than 15 tubes rupture during a main steam line break, the system response could lead to core melting. Although spontaneous and induced steam generator tube ruptures are small contributors to the total core damage frequency calculated in probabilistic risk assessments, they are risk significant because the radionuclides are likely to bypass the reactor containment building. The frequency of steam generator tube ruptures can be significantly reduced through appropriate and timely inspections and repairs or removal from service.

  11. Natural language generation

    NASA Astrophysics Data System (ADS)

    Maybury, Mark T.

    The goal of natural language generation is to replicate human writers or speakers: to generate fluent, grammatical, and coherent text or speech. Produced language, using both explicit and implicit means, must clearly and effectively express some intended message. This demands the use of a lexicon and a grammar together with mechanisms which exploit semantic, discourse and pragmatic knowledge to constrain production. Furthermore, special processors may be required to guide focus, extract presuppositions, and maintain coherency. As with interpretation, generation may require knowledge of the world, including information about the discourse participants as well as knowledge of the specific domain of discourse. All of these processes and knowledge sources must cooperate to produce well-written, unambiguous language. Natural language generation has received less attention than language interpretation due to the nature of language: it is important to interpret all the ways of expressing a message but we need to generate only one. Furthermore, the generative task can often be accomplished by canned text (e.g., error messages or user instructions). The advent of more sophisticated computer systems, however, has intensified the need to express multisentential English.

  12. Fuel cell generator

    DOEpatents

    Makiel, Joseph M.

    1985-01-01

    A high temperature solid electrolyte fuel cell generator comprising a housing means defining a plurality of chambers including a generator chamber and a combustion products chamber, a porous barrier separating the generator and combustion product chambers, a plurality of elongated annular fuel cells each having a closed end and an open end with the open ends disposed within the combustion product chamber, the cells extending from the open end through the porous barrier and into the generator chamber, a conduit for each cell, each conduit extending into a portion of each cell disposed within the generator chamber, each conduit having means for discharging a first gaseous reactant within each fuel cell, exhaust means for exhausting the combustion product chamber, manifolding means for supplying the first gaseous reactant to the conduits with the manifolding means disposed within the combustion product chamber between the porous barrier and the exhaust means and the manifolding means further comprising support and bypass means for providing support of the manifolding means within the housing while allowing combustion products from the first and a second gaseous reactant to flow past the manifolding means to the exhaust means, and means for flowing the second gaseous reactant into the generator chamber.

  13. Electronic signal generators: A compilation

    NASA Technical Reports Server (NTRS)

    1971-01-01

    Electronic signal generator data based on solid state concepts were simplified or refined to meet requirements, such as reliability, simplicity, fail-safe characteristics, and the capability of withstanding environmental extremes. Pulse generators, high voltage pulse generators, oscillators, analog signal generators, square wave signal generators, and special function signal generators are described.

  14. Generation of aptamer for biosensing applications

    NASA Astrophysics Data System (ADS)

    Gopinath, Subash C. B.; Hashim, U.; Arshad, M. K. Md.; Ruslinda, A. R.

    2016-07-01

    Systematic evolution of ligands by exponential enrichment (SELEX), an in vitro strategy which involves generation of aptamer. Aptamer is an artificial antibody, behave very similar to antibody and several instances reported to be better than antibodies. In this study, an attempt has been made to generate aptamer against factor IX, a potential candidate involve in human blood coagulation cascade. Totally, 10 selection cycles have been performed and molecules from 10th cycle have shown higher binding affinity with factor IX as 56 and 68% against the factor IX concentrations of 100 and 200 nM, respectively. With these higher binding affinities, it is clear that these molecules have higher potential for sensing applications.

  15. New Generator Technology

    SciTech Connect

    Nielsen, Roy S.

    2015-02-17

    New generator technology project is driven by the need to be able to remotely deploy generator technology where it is needed, when it is needed. Both the military and aid programs that provide assistance after disasters could use the ability to deploy energy generation that fits the needs of the situation. Currently, pre-specified generators are deployed, sometime more than half way around the world to provide electricity. Through our Phase-I to Phase III DARPA grant, we will provide a mechanism where a 3d print station and raw materials could be shipped to a deployment site and remotely deployed personnel. These remote personnel can collaborate with engineers at a home location where 3d print plans can be optimized for the remote purpose. The plans can then be sent electronically to the remote location for printing, much like NASA sent the plans for a socket wrench to the International Space Station for printing in . If multiple generators need to be deployed at different remote locations, within miles of each other the printer rig can be moved to print the generators where they are needed. 3d printing is growing in the field of manufacturing. 3d printing has matured to the point where many types of materials are now available for many types of manufacturing. Both magnetic and electrically conductive material materials have recently been developed which can now lead to 3d printing of engines and generators. Our project will provide a successful printer rig that can be remotely deployed, to print a generator design in the field as well as provide a process for deploying the printed generator as well. This Systems Engineering Management Plan(SEMP) will provide the planning required for a Phase I DARPA grant that may also include goals for Phase II and Phase II grants. The SEMP provides a proposed project schedule, references, system engineering processes, specialty engineering system deployment and product support sections. Each section will state how our company

  16. MCNP LWR Core Generator

    SciTech Connect

    Fischer, Noah A.

    2012-08-14

    The reactor core input generator allows for MCNP input files to be tailored to design specifications and generated in seconds. Full reactor models can now easily be created by specifying a small set of parameters and generating an MCNP input for a full reactor core. Axial zoning of the core will allow for density variation in the fuel and moderator, with pin-by-pin fidelity, so that BWR cores can more accurately be modeled. LWR core work in progress: (1) Reflectivity option for specifying 1/4, 1/2, or full core simulation; (2) Axial zoning for moderator densities that vary with height; (3) Generating multiple types of assemblies for different fuel enrichments; and (4) Parameters for specifying BWR box walls. Fuel pin work in progress: (1) Radial and azimuthal zoning for generating further unique materials in fuel rods; (2) Options for specifying different types of fuel for MOX or multiple burn assemblies; (3) Additional options for replacing fuel rods with burnable poison rods; and (4) Control rod/blade modeling.

  17. Simple sweep frequency generator

    NASA Astrophysics Data System (ADS)

    Yegorov, I.

    1985-01-01

    A sweep frequency generator is described whose center frequency can be varied from 10 kHz to 50 MHz, with seven 1 to 3 and 3 to 10 scales covering the 10 kHz to 30 MHz range and one 3 to 5 scale for the 30 to 50 MHz range. It consists of a tunable pulse generator with output voltage attenuator, a diode mixer for calibration, and a sawtooth voltage generator as a source of frequency deviation. The pulse generator is a multivibrator with two emitter coupled transistors and two diodes in the collector circuit of one. The first diode extends the tuning range and increases the frequency deviation, the second diode provides the necessary base bias to the other transistor. The pulse repetition rate is modulated either directly by the sweep voltage of the calibrating oscilloscope, this voltage being applied to the base of the transistor with the two diodes in its collector circuit through an additional attenuator or a special emitter follower, or by the separate sawtooth voltage generator. The latter is a conventional two transistor multivibrator and produces signals at any constant frequency within the 40 to 60 Hz range. The mixer receives unmodulated signals from a reference frequency source and produces different frequency signals which are sent through an RCR-filter to a calibrating oscilloscope.

  18. MHD Generating system

    DOEpatents

    Petrick, Michael; Pierson, Edward S.; Schreiner, Felix

    1980-01-01

    According to the present invention, coal combustion gas is the primary working fluid and copper or a copper alloy is the electrodynamic fluid in the MHD generator, thereby eliminating the heat exchangers between the combustor and the liquid-metal MHD working fluids, allowing the use of a conventional coalfired steam bottoming plant, and making the plant simpler, more efficient and cheaper. In operation, the gas and liquid are combined in a mixer and the resulting two-phase mixture enters the MHD generator. The MHD generator acts as a turbine and electric generator in one unit wherein the gas expands, drives the liquid across the magnetic field and thus generates electrical power. The gas and liquid are separated, and the available energy in the gas is recovered before the gas is exhausted to the atmosphere. Where the combustion gas contains sulfur, oxygen is bubbled through a side loop to remove sulfur therefrom as a concentrated stream of sulfur dioxide. The combustor is operated substoichiometrically to control the oxide level in the copper.

  19. Superconducting thermoelectric generator

    DOEpatents

    Metzger, J.D.; El-Genk, M.S.

    1994-01-01

    Thermoelectricity is produced by applying a temperature differential to dissimilar electrically conducting or semiconducting materials, thereby producing a voltage that is proportional to the temperature difference. Thermoelectric generators use this effect to directly convert heat into electricity; however, presently-known generators have low efficiencies due to the production of high currents which in turn cause large resistive heating losses. Some thermoelectric generators operate at efficiencies between 4% and 7% in the 800{degrees} to 1200{degrees}C range. According to its major aspects and bradly stated, the present invention is an apparatus and method for producing electricity from heat. In particular, the invention is a thermoelectric generator that juxtaposes a superconducting material and a semiconducting material - so that the superconducting and the semiconducting materials touch - to convert heat energy into electrical energy without resistive losses in the temperature range below the critical temperature of the superconducting material. Preferably, an array of superconducting material is encased in one of several possible configurations within a second material having a high thermal conductivity, preferably a semiconductor, to form a thermoelectric generator.

  20. Power Generation and the Environment

    PubMed Central

    Eliassen, Rolf

    1971-01-01

    Environmental factors will play an ever-increasing role in planning for the location and design of future power generating plants. This planning must include all phases of furnishing electric power, such as the exploration for and mining of fossil and nuclear fuels; the transportation and storage of these fuels; power plant siting; the disposal of solid wastes from power plants; and the transmission and distribution of electric power. Systems analysis will be of assistance in realistic decision-making and planning. Simulation models can be used to evaluate social, economic, and technological inputs, in order to reach engineering decisions that will assure meeting reasonable environmental standards. Management must look beyond the metropolitan areas presently served by specific electric utilities and must adopt new concepts of both urban and regional planning that will help meet the electric power requirements in the decades ahead and minimize adverse effects on the air, water, and land environment. Images