Sample records for adult cf cells

  1. SERCA2 Regulates Non-CF and CF Airway Epithelial Cell Response to Ozone

    PubMed Central

    Ahmad, Shama; Nichols, David P.; Strand, Matthew; Rancourt, Raymond C.; Randell, Scott H.; White, Carl W.; Ahmad, Aftab

    2011-01-01

    Calcium mobilization can regulate a wide range of essential functions of respiratory epithelium, including ion transport, ciliary beat frequency, and secretion of mucus, all of which are modified in cystic fibrosis (CF). SERCA2, an important controller of calcium signaling, is deficient in CF epithelium. We conducted this study to determine whether SERCA2 deficiency can modulate airway epithelial responses to environmental oxidants such as ozone. This could contribute to the pathogenesis of pulmonary exacerbations, which are important and frequent clinical events in CF. To address this, we used air-liquid interface (ALI) cultures of non-CF and CF cell lines, as well as differentiated cultures of cells derived from non-CF and CF patients. We found that ozone exposure caused enhanced membrane damage, mitochondrial dysfunction and apoptotic cell death in CF airway epithelial cell lines relative to non-CF. Ozone exposure caused increased proinflammatory cytokine production in CF airway epithelial cell lines. Elevated proinflammatory cytokine production also was observed in shRNA-mediated SERCA2 knockdown cells. Overexpression of SERCA2 reversed ozone-induced proinflammatory cytokine production. Ozone-induced proinflammatory cytokine production was NF-κB- dependent. In a stable NF-κB reporter cell line, SERCA2 inhibition and knockdown both upregulated cytomix-induced NF-κB activity, indicating importance of SERCA2 in modulating NF-κB activity. In this system, increased NF-κB activity was also accompanied by increased IL-8 production. Ozone also induced NF-κB activity and IL-8 release, an effect that was greater in SERCA2-silenced NF-κB-reporter cells. SERCA2 overexpression reversed cytomix-induced increased IL-8 release and total nuclear p65 in CFTR-deficient (16HBE-AS) cells. These studies suggest that SERCA2 is an important regulator of the proinflammatory response of airway epithelial cells and could be a potential therapeutic target. PMID:22096575

  2. Enhancement of discharge performance of Li/CF x cell by thermal treatment of CF x cathode material

    NASA Astrophysics Data System (ADS)

    Zhang, Sheng S.; Foster, Donald; Read, Jeffrey

    In this work we demonstrate that the thermal treatment of CF x cathode material just below the decomposition temperature can enhance discharge performance of Li/CF x cells. The performance enhancement becomes more effective when heating a mixture of CF x and citric acid (CA) since CA serves as an extra carbon source. Discharge experiments show that the thermal treatment not only reduces initial voltage delay, but also raises discharge voltage. Whereas the measurement of powder impedance indicates the thermal treatment does not increase electronic conductivity of CF x material. Based on these facts, we propose that the thermal treatment results in a limited decomposition of CF x, which yields a subfluorinated carbon (CF x- δ), instead of a highly conductive carbon. In the case of CF x/AC mixture, the AC provides extra carbon that reacts with F 2 and fluorocarbon radicals generated by the thermal decomposition of CF x to form subfluorinated carbon. The process of thermal treatment is studied by thermogravimetric analysis and X-ray diffraction, and the effect of treatment conditions such as heating temperature, heating time and CF x/CA ratio on the discharge performance of CF x cathode is discussed. As an example, a Li/CF x cell using CF x treated with CA at 500 °C under nitrogen for 2 h achieved theretical specific capacity when being discharged at C/5. Impedance analysis indicates that the enhanced performance is attributed to a significant reduction in the cell reaction resistance.

  3. Innovative CF program responds to the unique needs of adults.

    PubMed

    2006-03-01

    The median age of survival among CF patients has risen from 14 to nearly 40 over the past three decades, but these individuals have many different medical and psychosocial needs than the pediatric population. To better meet these needs, Atlanta-based Emory University Medical School has developed a distinct program for adult patients that provides multidisciplinary care to older CF patients from throughout the Southeast.

  4. Clostridium difficile carriage in adult cystic fibrosis (CF); implications for patients with CF and the potential for transmission of nosocomial infection.

    PubMed

    Burke, D G; Harrison, M J; Fleming, C; McCarthy, M; Shortt, C; Sulaiman, I; Murphy, D M; Eustace, J A; Shanahan, F; Hill, C; Stanton, C; Rea, M C; Ross, R P; Plant, B J

    2017-03-01

    Clostridium difficile is an anaerobic Gram-positive, spore-forming, toxin-producing bacillus transmitted among humans through the faecal-oral route. Despite increasing carriage rates and the presence of C. difficile toxin in stool, patients with CF rarely appear to develop typical manifestations of C. difficile infection (CDI). In this study, we examined the carriage, toxin production, ribotype distribution and antibiotic susceptibility of C. difficile in a cohort of 60 adult patients with CF who were pre-lung transplant. C. difficile was detected in 50% (30/60) of patients with CF by culturing for the bacteria. C. difficile toxin was detected in 63% (19/30) of C. difficile-positive stool samples. All toxin-positive stool samples contained toxigenic C. difficile strains harbouring toxin genes, tcdA and tcdB. Despite the presence of C. difficile and its toxin in patient stool, no acute gastrointestinal symptoms were reported. Ribotyping of C. difficile strains revealed 16 distinct ribotypes (RT), 11 of which are known to be disease-causing including the hyper-virulent RT078. Additionally, strains RT002, RT014, and RT015, which are common in non-CF nosocomial infection were described. All strains were susceptible to vancomycin, metronidazole, fusidic acid and rifampicin. No correlation was observed between carriage of C. difficile or any characteristics of isolated strains and any recorded clinical parameters or treatment received. We demonstrate a high prevalence of hypervirulent, toxigenic strains of C. difficile in asymptomatic patients with CF. This highlights the potential role of asymptomatic patients with CF in nosocomial transmission of C. difficile. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  5. Mini-guts in a dish: Perspectives of adult Cystic Fibrosis (CF) patients and parents of young CF patients on organoid technology.

    PubMed

    Boers, Sarah N; de Winter-de Groot, Karin M; Noordhoek, Jacquelien; Gulmans, Vincent; van der Ent, Cornelis K; van Delden, Johannes J M; Bredenoord, Annelien L

    2018-03-06

    Organoid technology enables the cultivation of human tissues in a dish. Its precision medicine potential could revolutionize the Cystic Fibrosis (CF) field. We provide a first thematic exploration of the patient perspective on organoid technology to set the further research agenda, which is necessary for responsible development of this ethically challenging technology. 23 semi-structured qualitative interviews with 14 Dutch adult CF patients and 12 parents of young CF patients to examine their experiences, opinions, and attitudes regarding organoid technology. Four themes emerged: (1) Respondents express a close as well as a distant relationship to organoids; (2) the open-endedness of organoid technology sparks hopes and concerns, (3) commercial use evokes cautiousness. (4) Respondents mention the importance of sound consent procedures, long-term patient engagement, responsible stewardship, and stringent conditions for commercial use. The precision medicine potential of organoid technology can only be realized if the patient perspective is taken adequately into account. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  6. Musculoskeletal manifestations and rheumatic symptoms in patients with cystic fibrosis (CF) no observations of CF-specific arthropathy.

    PubMed

    Koch, Ann-Kristin; Brömme, Sabine; Wollschläger, Bettina; Horneff, Gerd; Keyszer, Gernot

    2008-09-01

    To determine the character and frequency of musculoskeletal manifestations and rheumatic symptoms in patients with cystic fibrosis (CF). Rheumatic symptoms and signs of 70 patients with CF (age 6 to 61 yrs) were determined by interview and clinical assessment. Age and sex-matched healthy volunteers served as a control group. In CF patients, laboratory measures and bone mineral density (BMD) were investigated. The data were correlated with the CF phenotype [Shwachman Score (ShS), Chrispin-Norman Score (ChNS), and pulmonary function tests (PFT)]. The prevalence of joint pain in the CF patients was 12.9%, with a mean duration of 7 days. Swollen joints were found in 4 patients. None fulfilled the criteria for rheumatoid arthritis or connective tissue disease. Adult CF patients complained more often about noninflammatory back pain and myalgia, and demonstrated reduced spine mobility and impaired everyday life functions compared with the controls. Symptomatic CF patients had elevated erythrocyte sedimentation rate and C-reactive protein levels and performed worse on the ShS, ChNS, and PFT than asymptomatic patients. Antibodies against exotoxin A of Pseudomonas aeruginosa and recombinant Aspergillus fumigatus allergen f4 were found more frequently in CF patients with arthralgia. BMD was decreased in adult patients with more severe CF. In CF patients, the prevalence of rheumatic symptoms increases with age and CF severity. Our data suggest an association of infections with P. aeruginosa and A. fumigatus with the occurrence of rheumatic symptoms. However, no association of CF with definite inflammatory joint or connective tissue diseases was observed, and no CF-specific pattern of musculoskeletal symptoms was seen.

  7. CF.sub.4 laser

    DOEpatents

    Wittig, Curt; Tiee, Joe J.

    1979-01-01

    A CF.sub.4 laser for producing near 16 .mu.m radiation utilizing a line tunable CO.sub.2 laser as an optical pumping source. The device uses a cryogenically cooled optically pumped cell containing molecular CF.sub.4 gas. An optical resonant cavity formed around the optically pumped cell induces oscillations of near 16 .mu.m radiation from the .nu..sub.2 +.nu..sub.4 .fwdarw..nu..sub.2 transition in the molecular CF.sub.4 gas.

  8. A randomized controlled trial of a new behavioral home-based nutrition education program, "Eat Well with CF," in adults with cystic fibrosis.

    PubMed

    Watson, Helen; Bilton, Diana; Truby, Helen

    2008-05-01

    Cystic fibrosis (CF) remains the most common genetically inherited disease in the white population and its prognosis is affected by nutritional status. Adults with the disease are now surviving longer and new strategies are required to ensure that they maintain optimal nutrition. This article reports preliminary data from a randomized controlled trial of a 10-week home-based behavioral nutrition intervention, "Eat Well with CF." Outcome measures of weight change over 6 and 12 months and changes in CF-specific nutrition knowledge score, self-efficacy score, reported dietary fat intake and health-related quality-of-life score were compared between the intervention group (n=34) and a standard care control group (n=34). The hypotheses to be tested were that adults with CF completing "Eat Well with CF" would have an improved nutritional status, improvement in specific nutrition knowledge, and an improvement in self-efficacy regarding their ability to cope with a special diet, compared to those receiving standard care. There were substantial improvements in the intervention group's specific CF nutrition knowledge score, self-efficacy score, and reported fat intake compared to control, but no substantial change in body mass index or health-related quality of life over time. Home-based nutrition education incorporating behavioral strategies can be an effective way to support adults with CF, enabling improvement in self-management skills in relation to diet and pancreatic enzyme replacement therapy. This study revealed gaps in basic nutrition knowledge and skills, inadequate knowledge of diet-disease links and pancreatic enzyme replacement therapy. These need to be identified when subjects progress from pediatric to adult care, and programs such as "Eat Well with CF" are a useful adjunct for registered dietitians trying to manage this diverse but growing population.

  9. VAPOR PRESSURES, LIQUID MOLAR VOLUMES, VAPOR NON- IDEALITY, AND CRITICAL PROPERTIES OF CF3OCF2CF2CF3, c-CF2CF2CF2CF2O, CF3OCF2OCF3, AND CF3OCF2CF2H

    EPA Science Inventory

    New measurements of the thermophysical properties of CF3OCF2CF2CF3 and c -CF2CF2CF2CF2O are reported from T ≈ 235 K to the critical region. Liquid-phase volumetric results for CF3OCF2OCF3 and CF3OCF2CF2H (235 < T/K < 303) are reported to supplement the information already availab...

  10. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770

    PubMed Central

    Van Goor, Fredrick; Hadida, Sabine; Grootenhuis, Peter D. J.; Burton, Bill; Cao, Dong; Neuberger, Tim; Turnbull, Amanda; Singh, Ashvani; Joubran, John; Hazlewood, Anna; Zhou, Jinglan; McCartney, Jason; Arumugam, Vijayalaksmi; Decker, Caroline; Yang, Jennifer; Young, Chris; Olson, Eric R.; Wine, Jeffery J.; Frizzell, Raymond A.; Ashlock, Melissa; Negulescu, Paul

    2009-01-01

    Cystic fibrosis (CF) is a fatal genetic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), a protein kinase A (PKA)-activated epithelial anion channel involved in salt and fluid transport in multiple organs, including the lung. Most CF mutations either reduce the number of CFTR channels at the cell surface (e.g., synthesis or processing mutations) or impair channel function (e.g., gating or conductance mutations) or both. There are currently no approved therapies that target CFTR. Here we describe the in vitro pharmacology of VX-770, an orally bioavailable CFTR potentiator in clinical development for the treatment of CF. In recombinant cells VX-770 increased CFTR channel open probability (Po) in both the F508del processing mutation and the G551D gating mutation. VX-770 also increased Cl− secretion in cultured human CF bronchial epithelia (HBE) carrying the G551D gating mutation on one allele and the F508del processing mutation on the other allele by ≈10-fold, to ≈50% of that observed in HBE isolated from individuals without CF. Furthermore, VX-770 reduced excessive Na+ and fluid absorption to prevent dehydration of the apical surface and increased cilia beating in these epithelial cultures. These results support the hypothesis that pharmacological agents that restore or increase CFTR function can rescue epithelial cell function in human CF airway. PMID:19846789

  11. Sensitivity of chloride efflux vs. transepithelial measurements in mixed CF and normal airway epithelial cell populations.

    PubMed

    Illek, Beate; Lei, Dachuan; Fischer, Horst; Gruenert, Dieter C

    2010-01-01

    While the Cl(-) efflux assays are relatively straightforward, their ability to assess the efficacy of phenotypic correction in cystic fibrosis (CF) tissue or cells may be limited. Accurate assessment of therapeutic efficacy, i.e., correlating wild type CF transmembrane conductance regulator (CFTR) levels with phenotypic correction in tissue or individual cells, requires a sensitive assay. Radioactive chloride ((36)Cl) efflux was compared to Ussing chamber analysis for measuring cAMP-dependent Cl(-) transport in mixtures of human normal (16HBE14o-) and cystic fibrosis (CF) (CFTE29o- or CFBE41o-, respectively) airway epithelial cells. Cell mixtures with decreasing amounts of 16HBE14o- cells were evaluated. Efflux and Ussing chamber studies on mixed populations of normal and CF airway epithelial cells showed that, as the number of CF cells within the population was progressively increased, the cAMP-dependent Cl(-) decreased. The (36)Cl efflux assay was effective for measuring Cl(-) transport when ≥ 25% of the cells were normal. If < 25% of the cells were phenotypically wild-type (wt), the (36)Cl efflux assay was no longer reliable. Polarized CFBE41o- cells, also homozygous for the ΔF508 mutation, were used in the Ussing chamber studies. Ussing analysis detected cAMP-dependent Cl(-) currents in mixtures with ≥1% wild-type cells indicating that Ussing analysis is more sensitive than (36)Cl efflux analysis for detection of functional CFTR. Assessment of CFTR function by Ussing analysis is more sensitive than (36)Cl efflux analysis. Ussing analysis indicates that cell mixtures containing 10% 16HBE14o- cells showed 40-50% of normal cAMP-dependent Cl(-) transport that drops off exponentially between 10-1% wild-type cells. Copyright © 2010 S. Karger AG, Basel.

  12. The CF Canada-Sick Kids Program in individual CF therapy: A resource for the advancement of personalized medicine in CF.

    PubMed

    Eckford, Paul D W; McCormack, Jacqueline; Munsie, Lise; He, Gengming; Stanojevic, Sanja; Pereira, Sergio L; Ho, Karen; Avolio, Julie; Bartlett, Claire; Yang, Jin Ye; Wong, Amy P; Wellhauser, Leigh; Huan, Ling Jun; Jiang, Jia Xin; Ouyang, Hong; Du, Kai; Klingel, Michelle; Kyriakopoulou, Lianna; Gonska, Tanja; Moraes, Theo J; Strug, Lisa J; Rossant, Janet; Ratjen, Felix; Bear, Christine E

    2018-04-20

    Therapies targeting certain CFTR mutants have been approved, yet variations in clinical response highlight the need for in-vitro and genetic tools that predict patient-specific clinical outcomes. Toward this goal, the CF Canada-Sick Kids Program in Individual CF Therapy (CFIT) is generating a "first of its kind", comprehensive resource containing patient-specific cell cultures and data from 100 CF individuals that will enable modeling of therapeutic responses. The CFIT program is generating: 1) nasal cells from drug naïve patients suitable for culture and the study of drug responses in vitro, 2) matched gene expression data obtained by sequencing the RNA from the primary nasal tissue, 3) whole genome sequencing of blood derived DNA from each of the 100 participants, 4) induced pluripotent stem cells (iPSCs) generated from each participant's blood sample, 5) CRISPR-edited isogenic control iPSC lines and 6) prospective clinical data from patients treated with CF modulators. To date, we have recruited 57 of 100 individuals to CFIT, most of whom are homozygous for F508del (to assess in-vitro: in-vivo correlations with respect to ORKAMBI response) or heterozygous for F508del and a minimal function mutation. In addition, several donors are homozygous for rare nonsense and missense mutations. Nasal epithelial cell cultures and matched iPSC lines are available for many of these donors. This accessible resource will enable development of tools that predict individual outcomes to current and emerging modulators targeting F508del-CFTR and facilitate therapy discovery for rare CF causing mutations. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  13. The CF-CARES primary palliative care model: A CF-specific structured assessment of symptoms, distress, and coping.

    PubMed

    Friedman, Deborah; Linnemann, Rachel W; Altstein, Lily L; Islam, Suhayla; Bach, Kieu-Tram; Lamb, Chelsea; Volpe, John; Doolittle, Caitlin; St John, Anita; O'Malley, Patricia J; Sawicki, Gregory S; Georgiopoulos, Anna M; Yonker, Lael M; Moskowitz, Samuel M

    2018-01-01

    Current palliative care tools do not address distressing chronic symptoms that are most relevant to cystic fibrosis. A CF-specific structured assessment based on a primary palliative care framework was administered to 41 adolescents and adults with CF. Descriptive and correlational analyses were conducted. Patients reported numerous physical and psychological symptoms (mean of 10 per patient), with psychological symptoms rated as more distressing. Anxiety (34%) and depression (44%) were prevalent and correlated with distress attributable to physical symptoms and difficulty with CF self-management, but did not correlate with disease severity. Individuals with CF, regardless of disease severity, face challenges managing symptom burden. Frequently reported symptoms are not consistently associated with distress, suggesting the importance of individualized evaluation. The CF-CARES (Coping, goal Assessment, and Relief from Evolving CF Symptoms) primary palliative care assessment model provides a framework for patients experiencing chronic symptoms to explore interventional options with their clinicians. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  14. Theoretical insight into OH- and Cl-initiated oxidation of CF3OCH(CF3)2 and CF3OCF2CF2H & fate of CF3OC(X•)(CF3)2 and CF3OCF2CF2X• radicals (X=O, O2)

    PubMed Central

    Bai, Feng-Yang; Ma, Yuan; Lv, Shuang; Pan, Xiu-Mei; Jia, Xiu-Juan

    2017-01-01

    In this study, the mechanistic and kinetic analysis for reactions of CF3OCH(CF3)2 and CF3OCF2CF2H with OH radicals and Cl atoms have been performed at the CCSD(T)//B3LYP/6-311++G(d,p) level. Kinetic isotope effects for reactions CF3OCH(CF3)2/CF3OCD(CF3)2 and CF3OCF2CF2H/CF3OCF2CF2D with OH and Cl were estimated so as to provide the theoretical estimation for future laboratory investigation. All rate constants, computed by canonical variational transition state theory (CVT) with the small-curvature tunneling correction (SCT), are in reasonable agreement with the limited experimental data. Standard enthalpies of formation for the species were also calculated. Atmospheric lifetime and global warming potentials (GWPs) of the reaction species were estimated, the large lifetimes and GWPs show that the environmental impact of them cannot be ignored. The organic nitrates can be produced by the further oxidation of CF3OC(•)(CF3)2 and CF3OCF2CF2• in the presence of O2 and NO. The subsequent decomposition pathways of CF3OC(O•)(CF3)2 and CF3OCF2CF2O• radicals were studied in detail. The derived Arrhenius expressions for the rate coefficients over 230–350 K are: k T(1) = 5.00 × 10−24T3.57 exp(−849.73/T), k T(2) = 1.79 × 10−24T4.84 exp(−4262.65/T), kT(3) = 1.94 × 10−24 T4.18 exp(−884.26/T), and k T(4) = 9.44 × 10−28T5.25 exp(−913.45/T) cm3 molecule−1 s−1. PMID:28067283

  15. Theoretical insight into OH- and Cl-initiated oxidation of CF3OCH(CF3)2 and CF3OCF2CF2H & fate of CF3OC(X•)(CF3)2 and CF3OCF2CF2X• radicals (X=O, O2)

    NASA Astrophysics Data System (ADS)

    Bai, Feng-Yang; Ma, Yuan; Lv, Shuang; Pan, Xiu-Mei; Jia, Xiu-Juan

    2017-01-01

    In this study, the mechanistic and kinetic analysis for reactions of CF3OCH(CF3)2 and CF3OCF2CF2H with OH radicals and Cl atoms have been performed at the CCSD(T)//B3LYP/6-311++G(d,p) level. Kinetic isotope effects for reactions CF3OCH(CF3)2/CF3OCD(CF3)2 and CF3OCF2CF2H/CF3OCF2CF2D with OH and Cl were estimated so as to provide the theoretical estimation for future laboratory investigation. All rate constants, computed by canonical variational transition state theory (CVT) with the small-curvature tunneling correction (SCT), are in reasonable agreement with the limited experimental data. Standard enthalpies of formation for the species were also calculated. Atmospheric lifetime and global warming potentials (GWPs) of the reaction species were estimated, the large lifetimes and GWPs show that the environmental impact of them cannot be ignored. The organic nitrates can be produced by the further oxidation of CF3OC(•)(CF3)2 and CF3OCF2CF2• in the presence of O2 and NO. The subsequent decomposition pathways of CF3OC(O•)(CF3)2 and CF3OCF2CF2O• radicals were studied in detail. The derived Arrhenius expressions for the rate coefficients over 230-350 K are: k T(1) = 5.00 × 10-24T3.57 exp(-849.73/T), k T(2) = 1.79 × 10-24T4.84 exp(-4262.65/T), kT(3) = 1.94 × 10-24 T4.18 exp(-884.26/T), and k T(4) = 9.44 × 10-28T5.25 exp(-913.45/T) cm3 molecule-1 s-1.

  16. VAPOR PRESSURES, LIQUID MOLAR VOLUMES, VAPOR NON- IDEALITIES, AND CRITICAL PROPERTIES OF SOME FLUORINATED ETHERS: CF3OCF2OCF3, CF3OCF2 CF2H, c-CF2CF2CF2O, CF3OCF2H, AND CF3OCH3; AND OF CCl3F AND CF2ClH

    EPA Science Inventory

    Vapor pressures, compressibilities, expansivities, and molar volumes of the liquid phase have been measured between room temperature and the critical temperature for a series of fluorinated ethers: CF3OCF2OCF3, CF3OCF2CF2H, c-CF2CF2CF2O, CF3OCF2H, and CF3OCH3. Vapor-phase non-ide...

  17. Children and young adults with CF in the USA have better lung function compared with the UK.

    PubMed

    Goss, Christopher H; MacNeill, Stephanie J; Quinton, Hebe B; Marshall, Bruce C; Elbert, Alexander; Knapp, Emily A; Petren, Kristofer; Gunn, Elaine; Osmond, Joanne; Bilton, Diana

    2015-03-01

    People with cystic fibrosis (CF) are managed differently in the USA and UK providing an opportunity to learn from differences in practice patterns. To compare cross-sectional demographics, practice patterns and clinical outcomes between US and UK CF patients. This was a cross-sectional study using 2010 data from patients in the US Cystic Fibrosis Foundation and the UK Cystic Fibrosis patient registries. The a priori outcome measures of interest were lung function and nutritional status. Descriptive statistics and two sample comparisons were performed. Stratification and multivariable linear regression were used to adjust for confounding. The study cohort included 13 777 children and 11 058 adults from the USA and 3968 children and 3965 adults from the UK. In children, mean body mass index centiles were similar. Lung function (FEV1 and FVC% predicted) was significantly higher in US patients ages 6-25 years of age. In a regression model adjusted for only age, FEV1% predicted was on average 3.31% of predicted (95% CI 2.65 to 3.96) higher in the USA compared with the UK. When adjusted for age, age at diagnosis, gender, pancreatic insufficiency and genotype, FEV1% predicted was on average 3.03% of predicted (95% CI 2.37 to 3.69) higher in the USA compared with the UK These differences persisted despite adjustment for possible confounders. Hypertonic saline and dornase alfa were much more commonly prescribed in US children. Children and young adults with CF have better lung function in the USA compared with the UK despite similar nutritional status. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Organelle Redox of CF and CFTR-Corrected Airway Epithelia

    PubMed Central

    Schwarzer, Christian; Illek, Beate; Suh, Jung H.; Remington, S. James; Fischer, Horst; Machen, Terry E.

    2014-01-01

    In cystic fibrosis reduced CFTR function may alter redox properties of airway epithelial cells. Redox-sensitive GFP (roGFP1) and imaging microscopy were used to measure redox potentials of cytosol, ER, mitochondria and cell surface of cystic fibrosis nasal epithelial cells and CFTR-corrected cells. We also measured glutathione and cysteine thiol redox states in cell lysates and apical fluids to provide coverage over a range of redox potentials and environments that might be affected by CFTR. As measured with roGFP1, redox potentials at the cell surface (~ -207 ±8 mV) and in the ER (~ -217 ±1 mV) and rates of regulation of the apical fluid and ER lumen following DTT treatment were similar for CF and CFTR-corrected cells. CF and CFTR-corrected cells had similar redox potentials in mitochondria (-344 ±9 mV) and cytosol (-322 ±7 mV). Oxidation of carboxy-dichlorodihydrofluoresceindiacetate and of apical Amplex Red occurred at equal rates in CF and CFTR-corrected cells. Glutathione and cysteine redox couples in cell lysates and apical fluid were equal in CF and CFTR-corrected cells. These quantitative estimates of organelle redox potentials combined with apical and cell measurements using small molecule couples confirmed there were no differences in redox properties of CF and CFTR-corrected cells. PMID:17603939

  19. A prospective pilot study of home monitoring in adults with cystic fibrosis (HOME-CF): protocol for a randomised controlled trial.

    PubMed

    Choyce, Jocelyn; Shaw, Karen L; Sitch, Alice J; Mistry, Hema; Whitehouse, Joanna L; Nash, Edward F

    2017-01-23

    Home monitoring has the potential to detect early pulmonary exacerbations in people with cystic fibrosis (CF), with consequent improvements in health outcomes and healthcare associated costs. This study aims to assess the effects of home monitoring on hospital admissions, quality of life, antibiotic requirements, exacerbation frequency, lung function, nutritional outcomes, anxiety, depression, costs and health outcomes, as well as the qualitative effects on the patient experience. This randomised controlled mixed-methods trial aims to recruit 100 adults with CF cared for in one large regional CF centre. Participants are randomly allocated 1:1 to the intervention group (twice-weekly home monitoring of symptoms measured by the Cystic Fibrosis Respiratory Symptom Diary - Chronic Respiratory Infection Symptom Score (CFRSD-CRISS) and Forced Expiratory Volume in one second (FEV 1 )) or a control group (routine clinical care) for the 12-month study period. Measurements are recorded at study visits at baseline, 3, 6, 9 and 12 months. Spirometry, body weight, co-morbidities, medications, hospital inpatient days, courses of antibiotics (oral and intravenous), pulmonary exacerbations (defined by the modified Fuchs criteria) are recorded at each study visit. Health status, capability and health economics are measured at each study visit by the Hospital Anxiety and Depression Scale (HADS), the ICEpop CAPability measure for Adults (ICECAP-A), EuroQol 5 dimensions (EQ-5D-5L) questionnaire and an adapted resource use questionnaire. The patient experience is assessed by semi-structured qualitative interviews at baseline and 12 months. Results from this study will help to determine the effect of home monitoring on inpatient bed days and quality of life in adults with CF, as well as other relevant health and health economic outcomes. This study protocol is registered with Clinicaltrials.gov ( NCT02994706 ), date registered 16 th July 2014.

  20. Evaluation of Li/CF(x)Cells For Aerospace Applications

    NASA Technical Reports Server (NTRS)

    Vaidyanathan, Hari; Rao, Gopalakrishna M.

    2007-01-01

    Panasonic commercialized LiICF(x) cell technology in the 1970's. This technology was a promising primary battery for Aerospace applications such as: Exploration missions, Launch vehicles, Tools and more. This technology offers Wide operation temperature range, Low self-discharge and High specific energy CF(x) cathode material has a theoretical specific energy of 2260 Wh/Kg. Specific energy however achieved as of now is only 10% of theoretical value unless used at a very low rate of C/1000. Research both at Government Labs and Industries is currently in progress to improve the performance. This viewgraph presentation describes the cells, and reviews the results of some of the research using tables and charts.

  1. Understanding of safety monitoring in clinical trials by individuals with CF or their parents: A qualitative analysis.

    PubMed

    Kern-Goldberger, Andrew S; Hessels, Amanda J; Saiman, Lisa; Quittell, Lynne M

    2018-03-14

    Recruiting both pediatric and adult participants for clinical trials in CF is currently of paramount importance as numerous new therapies are being developed. However, recruitment is challenging as parents of children with CF and adults with CF cite safety concerns as a principal barrier to enrollment. In conjunction with the CF Foundation (CFF) Data Safety Monitoring Board (DSMB), a pilot brochure was developed to inform patients and parents of the multiple levels of safety monitoring; the CFF simultaneously created an infographic representing the safety monitoring process. This study explores the attitudes and beliefs of CF patients and families regarding safety monitoring and clinical trial participation, and elicits feedback regarding the educational materials. Semi-structured interviews were conducted using a pre-tested interview guide and audio-recorded during routine CF clinic visits. Participants included 5 parents of children with CF <16years old; 5 adolescents and young adults with CF 16-21years old; and 5 adults with CF ≥22years old from pediatric and adult CF centers. The study team performed systematic text condensation analysis of the recorded interviews using an iterative process. Four major thematic categories with subthemes emerged as supported by exemplar quotations: attitudes toward clinical trials, safety values, conceptualizing the safety monitoring process, and priorities for delivery of patient education. Participant feedback was used to revise the pilot brochure; text was shortened, unfamiliar words clarified (e.g., "pipeline"), abbreviations eliminated, and redundancy avoided. Qualitative analysis of CF patient and family interviews provided insights into barriers to participation in clinical trials, safety concerns, perspectives on safety monitoring and educational priorities. We plan a multicenter study to determine if the revised brochure reduces knowledge, attitude and practice barriers regarding participation in CF clinical trials

  2. CF 6 engine diagnostics

    NASA Technical Reports Server (NTRS)

    Stricklin, R.

    1981-01-01

    A summary of the activities which led to defining deterioration rates of the CF6 family of engines, a description of what was learned, and an identification of means of conserving fuel based upon the program findings are presented. The program to define the deterioration levels and modes for the CF6 family of engines involved four distinct phases: analysis of inbound engine test results, analysis of airline cruise data, analysis of airline test cell data resulting from testing of refurbished engines, and inspection of engine hardware.

  3. Fourier Transform Infrared Spectroscopy of CF4 on the GEC Reference Cell

    NASA Technical Reports Server (NTRS)

    Rao, M. V. V. S.; Sharma, S. P.; Meyyappan, M.; Cruden, Brett A.; Arnold, Jim (Technical Monitor)

    2001-01-01

    Fourier Transform Infrared Spectroscopy (FTIR) has been used to characterize inductively coupled CF4 plasmas in a GEC Reference Cell in-situ In examining these FTIR spectra, several assumptions and approximations of FTIR analysis are addressed. This includes the density dependence of cross-sections, non-linear effects in the addition of overlapping bands and the effect of spatial variations in density and temperature, This analysis demonstrates that temperatures extracted from MR spectra may provide a poor estimate of the true neutral plasma temperature. The FTIR spectra are dominated by unreacted CF, accounting for 40-60% of the gas products. The amount of CF4 consumption is found to have a marked dependence on power, and is nearly independent of pressure in the range of 10-50 mtorr. Small amounts of C2F6 are observed at low power. Also observed are etching products from the quartz window SiF4 COF2 and CO which occur in approximately equal ratios and together account for less than 10% of the gas. The concentrations of these species are nearly independent of pressure. CFx radicals are below the detection limit of this apparatus (approx. 1012/cc).

  4. Atmospheric Chemistry of (CF3)2CHOCH3, (CF3)2CHOCHO, and CF3C(O)OCH3.

    PubMed

    Østerstrøm, Freja From; Wallington, Timothy J; Sulbaek Andersen, Mads P; Nielsen, Ole John

    2015-10-22

    Smog chambers with in situ FTIR detection were used to measure rate coefficients in 700 Torr of air and 296 ± 2 K of: k(Cl+(CF3)2CHOCH3) = (5.41 ± 1.63) × 10(-12), k(Cl+(CF3)2CHOCHO) = (9.44 ± 1.81) × 10(-15), k(Cl+CF3C(O)OCH3) = (6.28 ± 0.98) × 10(-14), k(OH+(CF3)2CHOCH3) = (1.86 ± 0.41) × 10(-13), and k(OH+(CF3)2CHOCHO) = (2.08 ± 0.63) × 10(-14) cm(3) molecule(-1) s(-1). The Cl atom initiated oxidation of (CF3)2CHOCH3 gives (CF3)2CHOCHO in a yield indistinguishable from 100%. The OH radical initiated oxidation of (CF3)2CHOCH3 gives the following products (molar yields): (CF3)2CHOCHO (76 ± 8)%, CF3C(O)OCH3 (16 ± 2)%, CF3C(O)CF3 (4 ± 1)%, and C(O)F2 (45 ± 5)%. The primary oxidation product (CF3)2CHOCHO reacts with Cl atoms to give secondary products (molar yields): CF3C(O)CF3 (67 ± 7)%, CF3C(O)OCHO (28 ± 3)%, and C(O)F2 (118 ± 12)%. CF3C(O)OCH3 reacts with Cl atoms to give: CF3C(O)OCHO (80 ± 8)% and C(O)F2 (6 ± 1)%. Atmospheric lifetimes of (CF3)2CHOCH3, (CF3)2CHOCHO, and CF3C(O)OCH3 were estimated to be 62 days, 1.5 years, and 220 days, respectively. The 100-year global warming potentials (GWPs) for (CF3)2CHOCH3, (CF3)2CHOCHO, and CF3C(O)OCH3 are estimated to be 6, 121, and 46, respectively. A comprehensive description of the atmospheric fate of (CF3)2CHOCH3 is presented.

  5. Pseudomonas aeruginosa lipopolysaccharide induces CF-like alteration of protein secretion by human tracheal gland cells.

    PubMed

    Kammouni, W; Figarella, C; Baeza, N; Marchand, S; Merten, M D

    1997-12-18

    Human tracheal gland (HTG) serous cells are now believed to play a major role in the physiopathology of cystic fibrosis. Because of the persistent inflammation and the specific infection by Pseudomonas aeruginosa in the lung, we looked for the action of the lipopolysaccharide (LPS) of this bacteria on human tracheal gland cells in culture by studying the secretion of the secretory leukocyte proteinase inhibitor (SLPI) which is a specific serous secretory marker of these cells. Treatment with Pseudomonas aeruginosa LPS resulted in a significant dose-dependent increase in the basal production of SLPI (+ 250 +/- 25%) whilst the SLPI transcript mRNA levels remained unchanged. This LPS-induced increase in secretion was inhibited by glucocorticoides. Furthermore, LPS treatment of HTG cells induces a loss of responsiveness to carbachol and isoproterenol but not to adenosine triphosphate. These findings indicate that HTG cells treated by Pseudomonas aeruginosa LPS have the same behavior as those previously observed with CF-HTG cells. Exploration by using reverse transcriptase polymerase chain reaction amplification showed that LPS downregulated cystic fibrosis transmembrane conductance regulator (CFTR) mRNA expression in HTG cells indicative of a link between CFTR function and consequent CF-like alteration in protein secretory process.

  6. Effects of the toxic benthic dinoflagellate Ostreopsis cf. ovata on fertilization and early development of the sea urchin Lytechinus variegatus.

    PubMed

    Neves, Raquel A F; Contins, Mariana; Nascimento, Silvia M

    2018-04-01

    Blooms of the benthic dinoflagellate Ostreopsis cf. ovata have been recorded with increasing frequency, intensity and geographic distribution. This dinoflagellate produces potent toxins that may cause mortality of marine invertebrates. Adults of sea urchins are commonly affected by O. cf. ovata exposure with evidence of spines loss and high mortality during periods of high dinoflagellate abundances. Here, we report on the effects of the toxic dinoflagellate O. cf. ovata on fertilization and early development of the sea urchin Lytechinus variegatus, a key ecological herbivore. Lytechinus variegatus eggs and sperm were experimentally exposed to different concentrations of Ostreopsis cf. ovata (4, 40, 400, and 4000 cells ml -1 ) to test the hypothesis that fertilization success, embryonic and larval development of the sea urchin are negatively affected by the toxic dinoflagellate even at low abundances. Reduced fertilization, developmental failures, embryo and larval mortality, and occurrence of abnormal offspring were evident after exposure to O. cf. ovata. Fertilization decreased when gametes were exposed to high O. cf. ovata abundances (400 and 4000 cells ml -1 ), but just the exposure to the highest abundance significantly reduced fertilization success. Sea urchin early development was affected by O. cf. ovata in a dose-dependent way, high dinoflagellate abundances fully inhibited the early development of L. variegatus. Ostreopsis cf. ovata significantly increased the mortality of sea urchin eggs and embryos in the first hours of exposure (∼1-3 h), regardless of dinoflagellate abundance. Abundances of 400 and 4000 O. cf. ovata cells ml -1 induced significantly higher mortality on sea urchin initial stages in the first hours, and no egg or embryo was found in these treatments after 18 h of incubation. The early echinopluteus larva was only reached in the control and in treatments with low Ostreopsis cf. ovata abundances (4 and 40 cells ml -1 ). The

  7. Improving the care of patients with cystic fibrosis (CF)

    PubMed Central

    Khan, Ahsan Aftab; Nash, Edward F; Whitehouse, Joanna; Rashid, Rifat

    2017-01-01

    Background The West Midlands Adult Cystic Fibrosis (CF) Centre based at Birmingham Heartlands Hospital provides care for adults with CF in the West Midlands. People with CF are prone to pulmonary exacerbations, which often require inpatient admission for intravenous antibiotics. We observed that the admission process was efficient during working hours (9:00–17:00, Monday–Friday) when the CF team are routinely available, but out-of-working hours, there were delays in these patients being clerked and receiving their first antibiotic dose. We were concerned that this was resulting in quality and potential safety issues by causing delays in starting treatment and prolonging hospital inpatient stays. We therefore undertook a quality improvement project (QIP) aimed at addressing these issues. An initial survey showed median time to clerk of 5 hours, with 60% of patients missing their first dose of antibiotics and mean length of stay of 16 days. Methods We applied the Plan-Do-Study-Act (PDSA) cycle approach, with the first PDSA cycle involving raising awareness of the issue through education to doctors, nurses and patients. Results This led to a reduction of median time to clerk from 5 to 2 hours with 23% of patients missing their first antibiotic dose and mean length of stay reducing to 14 days. The second cycle involved introducing an admissions checklist and displaying education posters around the hospital, resulting in median time to clerk remaining at 2 hours but only 20% of patients missing their first antibiotic dose and the mean length of stay remaining at 14 days. Conclusion This QIP has improved the out-of-hours admissions process for adults with CF in our centre. We plan to review the longer term effects of the project including sustainability, effects on clinical outcomes and patient satisfaction. PMID:28959778

  8. ERp29 Regulates ΔF508 and Wild-type Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Trafficking to the Plasma Membrane in Cystic Fibrosis (CF) and Non-CF Epithelial Cells*

    PubMed Central

    Suaud, Laurence; Miller, Katelyn; Alvey, Lora; Yan, Wusheng; Robay, Amal; Kebler, Catherine; Kreindler, James L.; Guttentag, Susan; Hubbard, Michael J.; Rubenstein, Ronald C.

    2011-01-01

    Sodium 4-phenylbutyrate (4PBA) improves the intracellular trafficking of ΔF508-CFTR in cystic fibrosis (CF) epithelial cells. The underlying mechanism is uncertain, but 4PBA modulates the expression of some cytosolic molecular chaperones. To identify other 4PBA-regulated proteins that might regulate ΔF508-CFTR trafficking, we performed a differential display RT-PCR screen on IB3-1 CF bronchiolar epithelial cells exposed to 4PBA. One transcript up-regulated by 4PBA encoded ERp29, a luminal resident of the endoplasmic reticulum (ER) thought to be a novel molecular chaperone. We tested the hypothesis that ERp29 is a 4PBA-regulated ER chaperone that influences ΔF508-CFTR trafficking. ERp29 mRNA and protein expression was significantly increased (∼1.5-fold) in 4PBA-treated IB3-1 cells. In Xenopus oocytes, ERp29 overexpression increased the functional expression of both wild-type and ΔF508-CFTR over 3-fold and increased wild-type cystic fibrosis transmembrane conductance regulator (CFTR) plasma membrane expression. In CFBE41o− WT-CFTR cells, expression of and short circuit currents mediated by CFTR decreased upon depletion of ERp29 as did maturation of newly synthesized CFTR. In IB3-1 cells, ΔF508-CFTR co-immunoprecipitated with endogenous ERp29, and overexpression of ERp29 led to increased ΔF508-CFTR expression at the plasma membrane. These data suggest that ERp29 is a 4PBA-regulated ER chaperone that regulates WT-CFTR biogenesis and can promote ΔF508-CFTR trafficking in CF epithelial cells. PMID:21525008

  9. ERp29 regulates DeltaF508 and wild-type cystic fibrosis transmembrane conductance regulator (CFTR) trafficking to the plasma membrane in cystic fibrosis (CF) and non-CF epithelial cells.

    PubMed

    Suaud, Laurence; Miller, Katelyn; Alvey, Lora; Yan, Wusheng; Robay, Amal; Kebler, Catherine; Kreindler, James L; Guttentag, Susan; Hubbard, Michael J; Rubenstein, Ronald C

    2011-06-17

    Sodium 4-phenylbutyrate (4PBA) improves the intracellular trafficking of ΔF508-CFTR in cystic fibrosis (CF) epithelial cells. The underlying mechanism is uncertain, but 4PBA modulates the expression of some cytosolic molecular chaperones. To identify other 4PBA-regulated proteins that might regulate ΔF508-CFTR trafficking, we performed a differential display RT-PCR screen on IB3-1 CF bronchiolar epithelial cells exposed to 4PBA. One transcript up-regulated by 4PBA encoded ERp29, a luminal resident of the endoplasmic reticulum (ER) thought to be a novel molecular chaperone. We tested the hypothesis that ERp29 is a 4PBA-regulated ER chaperone that influences ΔF508-CFTR trafficking. ERp29 mRNA and protein expression was significantly increased (∼1.5-fold) in 4PBA-treated IB3-1 cells. In Xenopus oocytes, ERp29 overexpression increased the functional expression of both wild-type and ΔF508-CFTR over 3-fold and increased wild-type cystic fibrosis transmembrane conductance regulator (CFTR) plasma membrane expression. In CFBE41o- WT-CFTR cells, expression of and short circuit currents mediated by CFTR decreased upon depletion of ERp29 as did maturation of newly synthesized CFTR. In IB3-1 cells, ΔF508-CFTR co-immunoprecipitated with endogenous ERp29, and overexpression of ERp29 led to increased ΔF508-CFTR expression at the plasma membrane. These data suggest that ERp29 is a 4PBA-regulated ER chaperone that regulates WT-CFTR biogenesis and can promote ΔF508-CFTR trafficking in CF epithelial cells.

  10. Adult bone marrow-derived stem cells for the lung: implications for pediatric lung diseases.

    PubMed

    van Haaften, Timothy; Thébaud, Bernard

    2006-04-01

    Bronchopulmonary dysplasia (BPD) and cystic fibrosis (CF) are two common serious chronic respiratory disorders without specific treatments affecting children. BPD is characterized by an arrest in alveolar growth in premature infants requiring respiratory support. CF is the most common fatal inherited genetic disorder characterized by abnormally thick mucus secretions, recurrent infection and ultimately lung destruction. One commonality between these two diseases is the promise of utilizing stem cells therapeutically. Indeed, the use of exogenous cells to supplement the natural repair mechanisms or the possibility of genetic manipulation in vitro before administration are appealing therapeutic options for these diseases. Increasing attention has been focused on the use of adult bone marrow-derived stem cells (BMSC) to regenerate damaged organs such as the heart, the brain, and the liver. However, due to the lung's complexity as well as the low rate of cellular turnover within the lung, progress has been slower in this area compared with the skin or liver. Initial work suggests that BMSC can engraft and differentiate into a variety of lung cells, but these findings have been challenged recently. This article critically reviews the current advances on the therapeutic use of stem cells for lung regeneration.

  11. Toxicity and mode of action of insecticidal Cry1A proteins from Bacillus thuringiensis in an insect cell line, CF-1.

    PubMed

    Portugal, Leivi; Gringorten, J Lawrence; Caputo, Guido F; Soberón, Mario; Muñoz-Garay, Carlos; Bravo, Alejandra

    2014-03-01

    Bacillus thuringiensis Cry toxins are insecticidal proteins used to control insect pests. The interaction of Cry toxins with the midgut of susceptible insects is a dynamic process involving activation of the toxin, binding to midgut receptors in the apical epithelium and conformational changes in the toxin molecule, leading to pore formation and cell lysis. An understanding of the molecular events underlying toxin mode of action is essential for the continued use of Cry toxins. In this work, we examined the mechanism of action of Cry1A toxins in the lepidopteran cell line CF-1, using native Cry1Ab and mutant forms of this protein that interfer with different steps in the mechanism of action, specifically, receptor binding, oligomerization or pore formation. These mutants lost activity against both Manduca sexta larvae and CF-1 cells. We also analyzed a mutation created in domain I of Cry1Ab, in which helix α-1 and part of helix α-2 were deleted (Cry1AbMod). Cry1AbMod is able to oligomerize in the absence of toxin receptors, and although it shows reduced activity against some susceptible insects, it kills insect pests that have developed resistance to native Cry1Ab. Cry1AbMod showed enhanced toxicity to CF-1, suggesting that oligomerization of native Cry1Ab may be a limiting step in its activity against CF-1 cells. The toxicity of Cry1Ac and Cry1AcMod were also analyzed. Our results suggest that some of the steps in the mode of action of Cry1A toxins are conserved in vivo in insect midgut cells and in vitro in an established cell line, CF-1. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent

    PubMed Central

    Khan, Babar K.; Raz, Assaf; Rotolo, Jimmy A.; Wittekind, Michael

    2017-01-01

    ABSTRACT Biofilms pose a unique therapeutic challenge because of the antibiotic tolerance of constituent bacteria. Treatments for biofilm-based infections represent a major unmet medical need, requiring novel agents to eradicate mature biofilms. Our objective was to evaluate bacteriophage lysin CF-301 as a new agent to target Staphylococcus aureus biofilms. We used minimum biofilm-eradicating concentration (MBEC) assays on 95 S. aureus strains to obtain a 90% MBEC (MBEC90) value of ≤0.25 μg/ml for CF-301. Mature biofilms of coagulase-negative staphylococci, Streptococcus pyogenes, and Streptococcus agalactiae were also sensitive to disruption, with MBEC90 values ranging from 0.25 to 8 μg/ml. The potency of CF-301 was demonstrated against S. aureus biofilms formed on polystyrene, glass, surgical mesh, and catheters. In catheters, CF-301 removed all biofilm within 1 h and killed all released bacteria by 6 h. Mixed-species biofilms, formed by S. aureus and Staphylococcus epidermidis on several surfaces, were removed by CF-301, as were S. aureus biofilms either enriched for small-colony variants (SCVs) or grown in human synovial fluid. The antibacterial activity of CF-301 was further demonstrated against S. aureus persister cells in exponential-phase and stationary-phase populations. Finally, the antibiofilm activity of CF-301 was greatly improved in combinations with the cell wall hydrolase lysostaphin when tested against a range of S. aureus strains. In all, the data show that CF-301 is highly effective at disrupting biofilms and killing biofilm bacteria, and, as such, it may be an efficient new agent for treating staphylococcal infections with a biofilm component. PMID:28461319

  13. Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent.

    PubMed

    Schuch, Raymond; Khan, Babar K; Raz, Assaf; Rotolo, Jimmy A; Wittekind, Michael

    2017-07-01

    Biofilms pose a unique therapeutic challenge because of the antibiotic tolerance of constituent bacteria. Treatments for biofilm-based infections represent a major unmet medical need, requiring novel agents to eradicate mature biofilms. Our objective was to evaluate bacteriophage lysin CF-301 as a new agent to target Staphylococcus aureus biofilms. We used minimum biofilm-eradicating concentration (MBEC) assays on 95 S. aureus strains to obtain a 90% MBEC (MBEC 90 ) value of ≤0.25 μg/ml for CF-301. Mature biofilms of coagulase-negative staphylococci, Streptococcus pyogenes , and Streptococcus agalactiae were also sensitive to disruption, with MBEC 90 values ranging from 0.25 to 8 μg/ml. The potency of CF-301 was demonstrated against S. aureus biofilms formed on polystyrene, glass, surgical mesh, and catheters. In catheters, CF-301 removed all biofilm within 1 h and killed all released bacteria by 6 h. Mixed-species biofilms, formed by S. aureus and Staphylococcus epidermidis on several surfaces, were removed by CF-301, as were S. aureus biofilms either enriched for small-colony variants (SCVs) or grown in human synovial fluid. The antibacterial activity of CF-301 was further demonstrated against S. aureus persister cells in exponential-phase and stationary-phase populations. Finally, the antibiofilm activity of CF-301 was greatly improved in combinations with the cell wall hydrolase lysostaphin when tested against a range of S. aureus strains. In all, the data show that CF-301 is highly effective at disrupting biofilms and killing biofilm bacteria, and, as such, it may be an efficient new agent for treating staphylococcal infections with a biofilm component. Copyright © 2017 American Society for Microbiology.

  14. Purification and Characterization of a Glycerol-Resistant CF0-CF1 and CF1-ATPase from the Halotolerant Alga Dunaliella bardawil1

    PubMed Central

    Finel, Moshe; Pick, Uri; Selman-Reimer, Susanne; Selman, Bruce R.

    1984-01-01

    The isolation of the chloroplast ATP synthase complex (CF0-CF1) and of CF1 from Dunaliella bardawil is described. The subunit structure of the D. bardawil ATPase differs from that of the spinach in that the D. bardawil α subunit migrates ahead of the β subunit and ε-migrates ahead of subunit II of CF0 when separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The CF1 isolated from D. bardawil resembles the CF1 isolated from Chladmydomonas reinhardi in that a reversible, Mg2+-dependent ATPase is induced by selected organic solvents. Glycerol stimulates cyclic photophosphorylation catalyzed by D. bardawil thylakoid membranes but inhibits photophosphorylation catalyzed by spinach thylakoid membranes. Glycerol (20%) also stimulates the rate of ATP-Pi exchange catalyzed by D. bardawil CF0-CF1 proteoliposomes but inhibits the activity with the spinach enzyme. The ethanol-activated, Mg2+-ATPase of the D. bardawil CF1 is more resistant to glycerol inhibition than the octylglucoside-activated, Mg2+-ATPase of spinach CF1 or the ethanol-activated, Mg2+-dependent ATPase of the C. reinhardi CF1. Both cyclic photophosphorylation and ATP-Pi exchange catalyzed by D. bardawil CF0-CF1 are more sensitive to high concentrations of NaCl than is the spinach complex. Images Fig. 5 PMID:16663507

  15. 75 FR 22693 - Airworthiness Directives; General Electric Company (GE) CF34-1A, CF34-3A, and CF34-3B Series...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ..., Aerospace Engineer, Engine Certification Office, FAA, Engine & Propeller Directorate, 12 New England... Directives; General Electric Company (GE) CF34-1A, CF34-3A, and CF34-3B Series Turbofan Engines; Correction... to GE CF34-1A, CF34-3A, and CF34-3B series turbofan engines. The docket number is incorrect in all...

  16. Ablation of glutamate receptor GluRδ2 in adult Purkinje cells causes multiple innervation of climbing fibers by inducing aberrant invasion to parallel fiber innervation territory.

    PubMed

    Miyazaki, Taisuke; Yamasaki, Miwako; Takeuchi, Tomonori; Sakimura, Kenji; Mishina, Masayoshi; Watanabe, Masahiko

    2010-11-10

    Glutamate receptor GluRδ2 is exclusively expressed in Purkinje cells (PCs) from early development and plays key roles in parallel fiber (PF) synapse formation, elimination of surplus climbing fibers (CFs), long-term depression, motor coordination, and motor learning. To address its role in adulthood, we previously developed a mouse model of drug-induced GluRδ2 ablation in adult PCs (Takeuchi et al., 2005). In that study, we demonstrated an essential role to maintain the connectivity of PF-PC synapses, based on the observation that both mismatching of presynaptic and postsynaptic specializations and disconnection of PF-PC synapses are progressively increased after GluRδ2 ablation. Here, we pursued its role for CF wiring in adult cerebellum. In parallel with the disconnection of PF-PC synapses, ascending CF branches exhibited distal extension to innervate distal dendrites of the target and neighboring PCs. Furthermore, transverse CF branches, a short motile collateral rarely forming synapses in wild-type animals, displayed aberrant mediolateral extension to innervate distal dendrites of neighboring and remote PCs. Consequently, many PCs were wired by single main CF and other surplus CFs innervating a small part of distal dendrites. Electrophysiological recording further revealed that surplus CF-EPSCs characterized with slow rise time and small amplitude emerged after GluRδ2 ablation, and increased progressively both in number and amplitude. Therefore, GluRδ2 is essential for maintaining CF monoinnervation in adult cerebellum by suppressing aberrant invasion of CF branches to the territory of PF innervation. Thus, GluRδ2 fuels heterosynaptic competition and gives PFs the competitive advantages over CFs throughout the animal's life.

  17. Atmospheric chemistry of HFE-7000 (CF(3)CF (2)CF (2)OCH (3)) and 2,2,3,3,4,4,4-heptafluoro-1-butanol (CF (3)CF (2)CF (2)CH (2)OH): kinetic rate coefficients and temperature dependence of reactions with chlorine atoms.

    PubMed

    Díaz-de-Mera, Yolanda; Aranda, Alfonso; Bravo, Iván; Rodríguez, Diana; Rodríguez, Ana; Moreno, Elena

    2008-10-01

    The adverse environmental impacts of chlorinated hydrocarbons on the Earth's ozone layer have focused attention on the effort to replace these compounds by nonchlorinated substitutes with environmental acceptability. Hydrofluoroethers (HFEs) and fluorinated alcohols are currently being introduced in many applications for this purpose. Nevertheless, the presence of a great number of C-F bonds drives to atmospheric long-lived compounds with infrared absorption features. Thus, it is necessary to improve our knowledge about lifetimes and global warming potentials (GWP) for these compounds in order to get a complete evaluation of their environmental impact. Tropospheric degradation is expected to be initiated mainly by OH reactions in the gas phase. Nevertheless, Cl atoms reaction may also be important since rate constants are generally larger than those of OH. In the present work, we report the results obtained in the study of the reactions of Cl radicals with HFE-7000 (CF(3)CF(2)CF(2)OCH(3)) (1) and its isomer CF(3)CF(2)CF(2)CH(2)OH (2). Kinetic rate coefficients with Cl atoms have been measured using the discharge flow tube-mass spectrometric technique at 1 Torr of total pressure. The reactions of these chlorofluorocarbons (CFCs) substitutes have been studied under pseudo-first-order kinetic conditions in excess of the fluorinated compounds over Cl atoms. The temperature ranges were 266-333 and 298-353 K for reactions of HFE-7000 and CF(3)CF(2)CF(2)CH(2)OH, respectively. The measured room temperature rate constants were k(Cl+CF(3)CF(2)CF(2)OCH(3)) = (1.24 +/- 0.28) x 10(-13) cm(3) molecule(-1) s(-1)and k(Cl+CF(3)CF(2)CF(2)CH(2)OH) = (8.35 +/- 1.63) x 10(-13) cm(3) molecule(-1) s(-1) (errors are 2sigma + 10% to cover systematic errors). The Arrhenius expression for reaction 1 was k (1)(266-333 K) = (6.1 +/- 3.8) x 10(-13)exp[-(445 +/- 186)/T] cm(3) molecule(-1) s(-1) and k (2)(298-353 K) = (1.9 +/- 0.7) x 10(-12)exp[-(244 +/- 125)/T] cm(3) molecule(-1) s(-1) (errors

  18. CF-related diabetes: Containing the metabolic miscreant of cystic fibrosis.

    PubMed

    Moheet, Amir; Moran, Antoinette

    2017-11-01

    Cystic fibrosis-related diabetes (CFRD) is associated with both an increase in morbidity and mortality in people with cystic fibrosis (CF). With increased screening and improved life expectancy of people with CF, the prevalence of CFRD is expected to rise further. The underlying pathophysiological mechanisms causing glucose intolerance and diabetes in patients with CF are not well understood but both functional and structural abnormalities in islet cells are likely to have key roles. Insulin therapy improves health outcomes in patients with CF. Future research is needed to better understand the mechanisms underlying the development of CFRD and to develop new screening and treatment strategies to minimize the detrimental impact of CFRD on health outcomes in people with CF. © 2017 Wiley Periodicals, Inc.

  19. Infectious hematopoietic necrosis virus detected by separation and incubation of cells from salmonid cavity fluid.

    USGS Publications Warehouse

    Mulcahy, D.; Batts, W.N.

    1987-01-01

    Infectious hematopoietic necrosis (IHN) virus is usually detected by inoculating susceptible cell cultures with cavity ("ovarian") fluid (CF) from spawning females. We identified additional adult carriers of virus in spawning populations of steelhead trout (Salmo gairdneri) and sockeye salmon (Oncorhynchus nerka) by collecting nonerythrocytic cells from CF samples by low-speed centrifugation, culturing the cells for at least 7 d at 15 °C, and then testing the culture medium for virus. Virus appeared in the cultured cells from some samples of CF that remained negative during incubation. In additional samples of CF from these species, the virus titer increased in cultured cells compared with the titer in the original CF sample. With chinook salmon (O.tshawytscha), no negative samples converted to positive during incubation, but the virus titer was retained in incubated CF cells, but not in cell-free CF.

  20. Enterococcus faecalis Sex Pheromone cCF10 Enhances Conjugative Plasmid Transfer In Vivo.

    PubMed

    Hirt, Helmut; Greenwood-Quaintance, Kerryl E; Karau, Melissa J; Till, Lisa M; Kashyap, Purna C; Patel, Robin; Dunny, Gary M

    2018-02-13

    Cell-cell communication mediated by peptide pheromones (cCF10 [CF]) is essential for high-frequency plasmid transfer in vitro in Enterococcus faecalis To examine the role of pheromone signaling in vivo , we established either a CF-producing (CF+) recipient or a recipient producing a biologically inactive variant of CF (CF- recipient) in a germfree mouse model 3 days before donor inoculation and determined transfer frequencies of the pheromone-inducible plasmid pCF10. Plasmid transfer was detected in the upper and middle sections of the intestinal tract 5 h after donor inoculation and was highly efficient in the absence of antibiotic selection. The transconjugant/donor ratio reached a maximum level approaching 1 on day 4 in the upper intestinal tract. Plasmid transfer was significantly lower with the CF- recipient. While rescue of the CF- mating defect by coculture with CF+ recipients is easily accomplished in vitro , no extracellular complementation occurred in vivo This suggests that most pheromone signaling in the gut occurs between recipient and donor cells in very close proximity. Plasmid-bearing cells (donors plus transconjugants) steadily increased in the population from 0.1% after donor inoculation to about 10% at the conclusion of the experiments. This suggests a selective advantage of pCF10 carriage distinct from antibiotic resistance or bacteriocin production. Our results demonstrate that pheromone signaling is required for efficient pCF10 transfer in vivo In the absence of CF+ recipients, a low level of transfer to CF- recipients occurred in the gut. This may result from low-level host-mediated induction of the donors in the gastrointestinal (GI) tract, similar to that previously observed in serum. IMPORTANCE Horizontal gene transfer is a major factor in the biology of Enterococcus faecalis , an important nosocomial pathogen. Previous studies showing efficient conjugative plasmid transfer in the gastrointestinal (GI) tracts of experimental animals did

  1. Intravenous fosfomycin for pulmonary exacerbation of cystic fibrosis: Real life experience of a large adult CF centre.

    PubMed

    Spoletini, G; Kennedy, M; Flint, L; Graham, T; Etherington, C; Shaw, N; Whitaker, P; Denton, M; Clifton, I; Peckham, D

    2018-04-13

    The increased prevalence of multi-drug resistant strains of P.aeruginosa and allergic reactions among adult patients with cystic fibrosis (CF) limits the number of antibiotics available to treat pulmonary exacerbations. Fosfomycin, a unique broad spectrum bactericidal antibiotic, might offer an alternative therapeutic option in such cases. To describe the clinical efficacy, safety and tolerability of intravenous fosfomycin in combination with a second anti-pseudomonal antibiotic to treat pulmonary exacerbations in adult patients with CF. A retrospective analysis of data captured prospectively, over a 2-years period, on the Unit electronic medical records for patients who received IV fosfomycin was performed. Baseline characteristics in the 12 months prior treatment, lung function, CRP, renal and liver function and electrolytes at start and end of treatment were retrieved. 54 patients received 128 courses of iv fosfomycin in combination with a second antibiotic, resulting in improved FEV1 (0.94 L vs 1.24 L, p < 0.01) and reduced CRP (65 mg/L vs 19.3 mg/L, p < 0.01). Renal function pre- and post-treatment remained stable. 4% (n = 5) of courses were complicated with AKI at mid treatment, which resolved at the end of the course. Electrolyte supplementation was required in 18% of cases for potassium and magnesium and 7% for phosphate. Nausea was the most common side effects (48%), but was well controlled with anti-emetics. Antibiotic regimens including fosfomycin appear to be clinically effective and safe. Fosfomycin should, therefore, be considered as an add-on therapy in patients who failed to respond to initial treatment and with multiple drug allergies. Copyright © 2018. Published by Elsevier Ltd.

  2. Serum insulin-like growth factor-1 (IGF-1) during CF pulmonary exacerbation: trends and biomarker correlations.

    PubMed

    Gifford, A H; Nymon, A B; Ashare, A

    2014-04-01

    Cystic fibrosis (CF) is characterized by low circulating levels of insulin-like growth factor-1 (IGF-1), a hormone produced by the liver that governs anabolism and influences immune cell function. Because treatment of CF pulmonary exacerbation (CFPE) often improves body weight and lung function, we questioned whether serum IGF-1 trends were emblematic of these responses. Initially, we compared serum levels between healthy adults with CF and controls of similar age. We then measured serum IGF-1 throughout the CFPE cycle. We also investigated correlations among IGF-1 and other serum biomarkers during CFPE. Anthopometric, spirometric, and demographic data were collected. Serum IGF-1 concentrations were measured by ELISA. CF subjects in their usual state of health had lower serum IGF-1 levels than controls. Serum IGF-1 concentrations fell significantly from baseline at the beginning of CFPE. Treatment with intravenous antibiotics was associated with significant improvement in serum IGF-1 levels, body mass index (BMI), and percent-predicted forced expiratory volume in 1 sec (FEV1 %). At early and late CFPE, serum IGF-1 was directly correlated with FEV1 %, serum iron, hemoglobin concentration, and transferrin saturation (TSAT) and indirectly correlated with alpha-1-antitrypsin. This study not only supports the paradigm that CF is characterized by IGF-1 deficiency but also that trends in lung function, nutritional status, and serum IGF-1 are related. Improvements in all three parameters after antibiotics for CFPE likely highlight the connection between lung function and nutritional status in CF. Close correlations among IGF-1 and iron-related hematologic parameters suggest that IGF-1 may participate in CF iron homeostasis, another process that is known to be influenced by CFPE. © 2013 Wiley Periodicals, Inc.

  3. Single-cell high resolution melting analysis: A novel, generic, pre-implantation genetic diagnosis (PGD) method applied to cystic fibrosis (HRMA CF-PGD).

    PubMed

    Destouni, A; Poulou, M; Kakourou, G; Vrettou, C; Tzetis, M; Traeger-Synodinos, J; Kitsiou-Tzeli, S

    2016-03-01

    Institutions offering CF-PGD face the challenge of developing and optimizing single cell genotyping protocols that should cover for the extremely heterogeneous CF mutation spectrum. Here we report the development and successful clinical application of a generic CF-PGD protocol to facilitate direct detection of any CFTR nucleotide variation(s) by HRMA and simultaneous confirmation of diagnosis through haplotype analysis. A multiplex PCR was optimized supporting co-amplification of any CFTR exon-region, along with 6 closely linked STRs. Single cell genotypes were established through HRM analysis following melting of the 2nd round PCR products and were confirmed by STR haplotype analysis of the 1st PCR products. The protocol was validated pre-clinically, by testing 208 single lymphocytes, isolated from whole blood samples from 4 validation family trios. Fifteen PGD cycles were performed and 103 embryos were biopsied. In 15 clinical PGD cycles, genotypes were achieved in 88/93 (94.6%) embryo biopsy samples, of which 57/88 (64.8%) were deemed genetically suitable for embryo transfer. Amplification failed at all loci for 10/103 blastomeres biopsied from poor quality embryos. Six clinical pregnancies were achieved (2 twin, 4 singletons). PGD genotypes were confirmed following conventional amniocentesis or chorionic villus sampling in all achieved pregnancies. The single cell HRMA CF-PGD protocol described herein is a flexible, generic, low cost and robust genotyping method, which facilitates the analysis of any CFTR genotype combination. Single-cell HRMA can be beneficial to other clinical settings, for example the detection of single nucleotide variants in single cells derived from clinical tumor samples. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  4. Ostreopsis cf. ovata dynamics in the NW Mediterranean Sea in relation to biotic and abiotic factors

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

    Carnicer, Olga; Guallar, Carles; IFREMER, DYNECO-PELAGOS Centre de Brest, Pointe du Diable BP70, 29280 Plouzane

    2015-11-15

    An expansion of the distribution of Ostreopsis cf. ovata, a dinoflagellate which produces palytoxin-like compounds, has been reported in recent years. Economical and social interests are affected by blooms, as they are responsible for respiratory and skin problems in humans and may cause damage to marine organisms. In order to identify the most influential environmental factors that trigger proliferations of O. cf. ovata in the area of the adjacent shallow rocky coast of the Ebro Delta (NW Mediterranean Sea) a three-year survey was performed on the metaphytic microalgae community growing on the macrophytes Jania rubens and Corallina elongata. Small-size diatomsmore » were more abundant than dinoflagellates; O. cf. ovata was identified as the only species present from the genus. Seawater temperature was the primary driver defining the ecological niche of O. cf. ovata. Freshwater and groundwater fluxes were more pronounced in southern than in northern sites, which may have resulted in a distinct O. cf. ovata spatial distribution, with the highest records of abundance and more frequent blooms in the north. In consequence, negative correlations between the abundance of O. cf. ovata and nitrate concentrations and significant positive correlation with salinity were observed. The temporal pattern of O. cf. ovata dynamics from mid-July to early-November is probably due to the fact that this species is observed only above a certain threshold temperature of seawater. Metaphytic cells of O. cf. ovata were smaller in the northern site than in the south, possibly as a result of an increase in cell division, coinciding with higher abundance, and this could be an indicator of favorable conditions. Toxicity in planktonic cells was negatively correlated with cell abundance in the water column, achieving maximum concentrations of 25 pg. PLTX eq cell{sup −1}. - Highlights: • Presence of a single Ostreopsis genotype in confirmed through qPCR. • Temperature confirmed as the

  5. Anabolic agent use in adults with cystic fibrosis.

    PubMed

    Green, Heather D; Barry, Peter J; Jones, Andrew M

    2015-10-01

    The use of non-prescribed anabolic agents amongst non-athletes is increasing with young, adult males with cystic fibrosis (CF) in the highest risk demographic. There is evidence that anabolic agents increase weight and muscle mass in adults with a variety of catabolic conditions but there is no evidence for their use in hormone sufficient adults with CF. We report a case of anabolic agent use in a male adult with CF and review the clinical features of anabolic agent use with a focus on adults with CF. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Cf-252 Characterization Documents

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

    Feldman, Alexander

    2014-03-14

    Six documents were written by Vance and Associates under contract to the Off-Site Source Recovery Project of Los Alamos National Laboratory. These Six documents provided the basis for characterization of Californium-252 sealed sources and for the packaging and manifesting of this material for disposal at the Waste Isolation Pilot Project. The Six documents are: 1. VA-OSR-10, Development of radionuclide distributions for Cf-252 sealed sources. 2. VA-OSR-11, Uncertainty analysis for Cf-252 sealed sources. 3. VA-OSR-12, To determine the radionuclides in the waste drums containing Cf-252 sealed source waste that are required to be reported under the requirements of the WIPP WACmore » and the TRAMPAC. 4. VA-OSR-13, Development of the spreadsheet for the radiological calculations for the characterization of Cf-252 sources. 5. VA-OSR-14, Relative importance of neutron-induced fission in Cf-252 sources. 6. VA-OSR-15, Determine upper bound of decay product inventories from a drum of Cf-252 sources. These six documents provide the technical basis for the characterization of Cf-252 sources and will be part of the AK documentation required for submittal to the Central Characterization Project (CCP) of WIPP.« less

  7. CfRadial - CF NetCDF for Radar and Lidar Data in Polar Coordinates.

    NASA Astrophysics Data System (ADS)

    Dixon, M. J.; Lee, W. C.; Michelson, D.; Curtis, M.

    2016-12-01

    Since 1990, NCAR has supported over 20 different data formats for radar and lidar data in polar coordinates. Researchers, students and operational users spend unnecessary time handling a multitude of unique formats. CfRadial grew out of the need to simplify the use of these data and thereby to improve efficiency in research and operations. CfRadial adopts the well-known NetCDF framework, along with the Climate and Forecasting (CF) conventions such that data and metadata are accurately represented. Mobile platforms are also supported. The first major release, CfRadial version 1.1, occurred in February 2011, followed by minor updates. CfRadial has been adopted by NCAR as well as other agencies in the US and the UK. CfRadial development was boosted in 2015 through a two-year NSF EarthCube grant to improve CF in general. Version 1.4 was agreed upon in May 2016, adding explicit support for quality control fields and spectra. In Europe and Australia, EUMETNET OPERA's HDF5-based ODIM_H5 standard has been rapidly embraced as the modern standard for exchanging weather radar data for operations. ODIM_H5 exploits data groups, hierarchies, and built-in compression, characteristics that have been added to NetCDF4. A meeting of the WMO Task Team on Weather Radar Data Exchange (TT-WRDE) was held at NCAR in Boulder in July 2016, with a goal of identifying a single global standard for radar and lidar data in polar coordinates. CfRadial and ODIM_H5 were considered alongside the older and more rigid table-driven WMO BUFR and GRIB2 formats. TT-WRDE recommended that CfRadial 1.4 be merged with the sweep-oriented structure of ODIM_H5, making use of NetCDF groups, to produce a single format that will encompass the best ideas of both formats. That has led to the emergence of the CfRadial 2.0 standard. This format should meet the objectives of both the NSF EarthCube CF 2.0 initiative and the WMO TT-WRDE. It has the added benefit of improving data exchange between operational and research

  8. Maternal cfDNA screening for Down syndrome--a cost sensitivity analysis.

    PubMed

    Cuckle, Howard; Benn, Peter; Pergament, Eugene

    2013-07-01

    This study aimed to determine the principal factors contributing to the cost of avoiding a birth with Down syndrome by using cell-free DNA (cfDNA) to replace conventional screening. A range of unit costs were assigned to each item in the screening process. Detection rates were estimated by meta-analysis and modeling. The marginal cost associated with the detection of additional cases using cfDNA was estimated from the difference in average costs divided by the difference in detection. The main factor was the unit cost of cfDNA testing. For example, replacing a combined test costing $150 with 3% false-positive rate and invasive testing at $1000, by cfDNA tests at $2000, $1500, $1000, and $500, the marginal cost is $8.0, $5.8, $3.6, and $1.4m, respectively. Costs were lower when replacing a quadruple test and higher for a 5% false-positive rate, but the relative importance of cfDNA unit cost was unchanged. A contingent policy whereby 10% to 20% women were selected for cfDNA testing by conventional screening was considerably more cost-efficient. Costs were sensitive to cfDNA uptake. Universal cfDNA screening for Down syndrome will only become affordable by public health purchasers if costs fall substantially. Until this happens, the contingent use of cfDNA is recommended. © 2013 John Wiley & Sons, Ltd.

  9. Photoionisation study of Xe.CF{sub 4} and Kr.CF{sub 4} van-der-Waals molecules

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

    Alekseev, V. A., E-mail: alekseev@va3474.spb.edu; Kevorkyants, R.; Garcia, G. A.

    2016-05-14

    We report on photoionization studies of Xe.CF{sub 4} and Kr.CF{sub 4} van-der-Waals complexes produced in a supersonic expansion and detected using synchrotron radiation and photoelectron-photoion coincidence techniques. The ionization potential of CF{sub 4} is larger than those of the Xe and Kr atoms and the ground state of the Rg.CF{sub 4}{sup +} ion correlates with Rg{sup +} ({sup 2}P{sub 3/2}) + CF{sub 4}. The onset of the Rg.CF{sub 4}{sup +} signals was found to be only ∼0.2 eV below the Rg ionization potential. In agreement with experiment, complementary ab initio calculations show that vertical transitions originating from the potential minimummore » of the ground state of Rg.CF{sub 4} terminate at a part of the potential energy surfaces of Rg.CF{sub 4}{sup +}, which are approximately 0.05 eV below the Rg{sup +} ({sup 2}P{sub 3/2}) + CF{sub 4} dissociation limit. In contrast to the neutral complexes, which are most stable in the face geometry, for the Rg.CF{sub 4}{sup +} ions, the calculations show that the minimum of the potential energy surface is in the vertex geometry. Experiments which have been performed only with Xe.CF{sub 4} revealed no Xe.CF{sub 4}{sup +} signal above the first ionization threshold of Xe, suggesting that the Rg.CF{sub 4}{sup +} ions are not stable above the first dissociation limit.« less

  10. Thermodynamic properties of seven gaseous halogenated hydrocarbons from acoustic measurements: CHClFCF3, CHF2 CF3, CF3 CH3, CHF2CH3, CF3CHFCHF2, CF3CH2CF3, and CHF2CF2CH2F

    NASA Astrophysics Data System (ADS)

    Gillis, K. A.

    1997-01-01

    Measurements of the speed of sound in seven halogenated hydrocarbons are presented. The compounds in this study are 1-chloro-1,2,2,2-tetrafluoroethane (CHClFCF3 or HCFC-124), pentafluoroethane (CHF2 CF3 or HFC-125), 1,1,1-trifluoroethane (CF3CH3 or HFC-143a), 1,1-difluoroethane (CHF2CH3 or HFC-152a), 1,1,1,2,3,3-hexafluoropropane (CF3CHFCHF2 or HFC-236ea), 1,1,1,3,3,3-hexafluoropropane (CF3CH2CF3 or HFC-236fa), and 1,1,2,2,3-pentafluoropropane (CHF2CF2CH2F or HFC-245ca). The measurements were performed with a cylindrical resonator at temperatures between 240 and 400 K and at pressures up to 1.0 MPa. Ideal-gas heat capacities and acoustic virial coefficients were directly deduced from the data. The ideal-gas heat capacity of HFC-125 from this work differs from spectroscopic calculations by less than 0.2% over the measurement range. The coefficients for virial equations of state were obtained from the acoustic data and hard-core square-well intermolecular potentials. Gas densities that were calculated from the virial equations of state for HCFC-124 and HFC-125 differ from independent density measurements by at most 0.15%, for the ranges of temperature and pressure over which both acoustic and Burnett data exist. The uncertainties in the derived properties for the other five compounds are comparable to those for HCFC-124 and HFC-125.

  11. Atmospheric chemistry of cyc-CF2CF2CF2CH=CH-: Kinetics, products, and mechanism of gas-phase reaction with OH radicals, and atmospheric implications

    NASA Astrophysics Data System (ADS)

    Guo, Qin; Zhang, Ni; Uchimaru, Tadafumi; Chen, Liang; Quan, Hengdao; Mizukado, Junji

    2018-04-01

    The rate constants for the gas-phase reactions of cyc-CF2CF2CF2CH=CH- with OH radicals were determined by a relative rate method between 253 and 328 K. The rate constant k1 at 298 K was measured to be (1.08 ± 0.04) × 10-13 cm3 molecule-1 s-1, and the Arrhenius expression was k1 = (3.72 ± 0.14) × 10-13 exp [(-370 ± 12)/T]. The atmospheric lifetime of cyc-CF2CF2CF2CH=CH- was calculated to be 107 d. The products and mechanism for the reaction of cyc-CF2CF2CF2CH=CH- with OH radicals were also investigated. CO, CO2, and COF2 were identified as the main carbon-containing products following the OH-initiated reaction. Moreover, the radiative efficiency (RE) was determined to be 0.143 W m-2 ppb-1, and the global warming potentials (GWPs) for 20, 100, and 500 yr were 54, 15, and 4, respectively. The photochemical ozone creation potential of the title compound was estimated to be 1.3.

  12. Reactivation of the chloroplast CF1-ATPase beta subunit by trace amounts of the CF1 alpha subunit suggests a chaperonin-like activity for CF1 alpha.

    PubMed

    Avni, A; Avital, S; Gromet-Elhanan, Z

    1991-04-25

    Incubation of tobacco and lettuce thylakoids with 2 M LiCl in the presence of MgATP removes the beta subunit from their CF1-ATPase (CF1 beta) together with varying amounts of the CF1 alpha subunit (CF1 alpha). These 2 M LiCl extracts, as with the one obtained from spinach thylakoids (Avital, S., and Gromet-Elhanan, Z. (1991) J. Biol. Chem. 266, 7067-7072), could form active hybrid ATPases when reconstituted into inactive beta-less Rhodospirillum rubrum chromatophores. Pure CF1 beta fractions that have been isolated from these extracts could not form such active hybrids by themselves, but could do so when supplemented with trace amounts (less than 5%) of CF1 alpha. A mitochondrial F1-ATPase alpha subunit was recently reported to be a heat-shock protein, having two amino acid sequences that show a highly conserved identity with sequences found in molecular chaperones (Luis, A. M., Alconada, A., and Cuezva, J. M. (1990) J. Biol. Chem. 265, 7713-7716). These sequences are also conserved in CF1 alpha isolated from various plants, but not in F1 beta subunits. The above described reactivation of CF1 beta by trace amounts of CF1 alpha could thus be due to a chaperonin-like function of CF1 alpha, which involves the correct, active folding of isolated pure CF1 beta.

  13. NASA CF6 jet engine diagnostics program: Long-term CF6-6D low-pressure turbine deterioration

    NASA Technical Reports Server (NTRS)

    Smith, J. J.

    1979-01-01

    Back-to-back performance tests were run on seven airline low pressure turbine (LPT) modules and four new CF6-6D modules. Back-to-back test cell runs, in which an airline LPT module was directly compared to a new production module, were included. The resulting change, measured in fuel burn, equaled the level of LPT module deterioration. Three of the LPT modules were analytically inspected followed by a back-to-back test cell run to evaluate current refurbishment techniques.

  14. CF6-6D engine performance deterioration

    NASA Technical Reports Server (NTRS)

    Wulf, R. H.; Kramer, W. H.; Pass, J. E.; Smith, J. J.

    1980-01-01

    Cruise cockpit recordings and test cell performance data in conjunction with hardware inspection data from airline overhaul shops were analyzed to define the extent and magnitude of performance deterioration of the General Electric CF6-6D model engine. These studies successfully isolated short-term deterioration from the longer term, and defined areas where a significant reduction in aircraft energy requirements for the 1980's can be realized. Unrestored losses which remain after engine refurbishment represent over 70% of the loss at engine shop visit. Sixty-three percent of the unrestored losses are cost-effective to restore which could reduce fuel consumed by CF6-6D engines in 1980 by 10.9 million gallons.

  15. Assessment of CF lung disease using motion corrected PROPELLER MRI: a comparison with CT.

    PubMed

    Ciet, Pierluigi; Serra, Goffredo; Bertolo, Silvia; Spronk, Sandra; Ros, Mirco; Fraioli, Francesco; Quattrucci, Serena; Assael, M Baroukh; Catalano, Carlo; Pomerri, Fabio; Tiddens, Harm A W M; Morana, Giovanni

    2016-03-01

    To date, PROPELLER MRI, a breathing-motion-insensitive technique, has not been assessed for cystic fibrosis (CF) lung disease. We compared this technique to CT for assessing CF lung disease in children and adults. Thirty-eight stable CF patients (median 21 years, range 6-51 years, 22 female) underwent MRI and CT on the same day. Study protocol included respiratory-triggered PROPELLER MRI and volumetric CT end-inspiratory and -expiratory acquisitions. Two observers scored the images using the CF-MRI and CF-CT systems. Scores were compared with intra-class correlation coefficient (ICC) and Bland-Altman plots. The sensitivity and specificity of MRI versus CT were calculated. MRI sensitivity for detecting severe CF bronchiectasis was 0.33 (CI 0.09-0.57), while specificity was 100% (CI 0.88-1). ICCs for bronchiectasis and trapped air were as follows: MRI-bronchiectasis (0.79); CT-bronchiectasis (0.85); MRI-trapped air (0.51); CT-trapped air (0.87). Bland-Altman plots showed an MRI tendency to overestimate the severity of bronchiectasis in mild CF disease and underestimate bronchiectasis in severe disease. Motion correction in PROPELLER MRI does not improve assessment of CF lung disease compared to CT. However, the good inter- and intra-observer agreement and the high specificity suggest that MRI might play a role in the short-term follow-up of CF lung disease (i.e. pulmonary exacerbations). PROPELLER MRI does not match CT sensitivity to assess CF lung disease. PROPELLER MRI has lower sensitivity than CT to detect severe bronchiectasis. PROPELLER MRI has good to very good intra- and inter-observer variability. PROPELLER MRI can be used for short-term follow-up studies in CF.

  16. Heterogeneous processes in CF4/O2 plasmas probed using laser-induced fluorescence of CF2

    NASA Astrophysics Data System (ADS)

    Hansen, S. G.; Luckman, G.; Nieman, George C.; Colson, Steven D.

    1990-09-01

    Laser-induced fluorescence of CF2 is used to monitor heterogeneous processes in ≊300 mTorr CF4/O2 plasmas. CF2 is rapidly removed at fluorinated copper and silver surfaces in 13.56-MHz rf discharges as judged by a distinct dip in its spatial distribution. These metals, when employed as etch masks, are known to accelerate plasma etching of silicon, and the present results suggest catalytic dehalogenation of CF2 is involved in this process. In contrast, aluminum and silicon dioxide exhibit negligible reactivity with CF2, which suggests that aluminum masks will not appreciably accelerate silicon etching and that ground state CF2 does not efficiently etch silicon dioxide. Measurement of CF2 decay in a pulsed discharge coupled with direct laser sputtering of metal into the gas phase indicates the interaction between CF2 and the active metals is purely heterogeneous. Aluminum does, however, exhibit homogeneous reactivity with CF2. Redistribution of active metal by plasma sputtering readily occurs; silicon etch rates may also be enhanced by the metal's presence on the silicon surface. Polymers contribute CF2 to the plasma as they etch. The observation of an induction period suggests fluorination of the polymer surface is the first step in its degradation. Polymeric etch masks can therefore depress the silicon etch rate by removal of F atoms, the primary etchants.

  17. AgS2O6CF3: the first trifluoromethylsulfonylsulfate(VI).

    PubMed

    Malinowski, Przemysław J; Derzsi, Mariana; Grochala, Wojciech

    2013-08-07

    We describe the synthetic route towards a novel class of salts, trifluoromethylsulfonylsulfates, as exemplified by the silver(I) derivative (AgS2O6CF3). Formation proceeds via direct reaction between a triflate precursor, AgSO3CF3, and SO3. The title compound crystallizes in the P2(1)/c unit cell with a = 5.15746(14) Å, b = 25.8563(9) Å, c = 5.53970(14) Å and β = 101.1749(19)°. The structure is layered with the puckered [AgS2O6] 2D sheets; the terminal CF3 groups are separated by the van der Waals gap, as seen also for related metal triflates. The compound is very fragile thermally and it decomposes endothermally to AgSO3CF3 with concomitant evolution of SO3 even at 65 °C or upon grinding in an agate mortar; thus it may serve as a solid store of--otherwise volatile and corrosive--SO3. The IR and Raman spectra of AgS2O6CF3 have been tentatively assigned based on similarities to those of related Ag2S2O7 and AgSO3CF3 and phonon calculations. Synthesis and properties of KS2O6CF3 are also briefly described.

  18. Measures of large-scale structure in the CfA redshift survey slices

    NASA Technical Reports Server (NTRS)

    De Lapparent, Valerie; Geller, Margaret J.; Huchra, John P.

    1991-01-01

    Variations of the counts-in-cells with cell size are used here to define two statistical measures of large-scale clustering in three 6 deg slices of the CfA redshift survey. A percolation criterion is used to estimate the filling factor which measures the fraction of the total volume in the survey occupied by the large-scale structures. For the full 18 deg slice of the CfA redshift survey, f is about 0.25 + or - 0.05. After removing groups with more than five members from two of the slices, variations of the counts in occupied cells with cell size have a power-law behavior with a slope beta about 2.2 on scales from 1-10/h Mpc. Application of both this statistic and the percolation analysis to simulations suggests that a network of two-dimensional structures is a better description of the geometry of the clustering in the CfA slices than a network of one-dimensional structures. Counts-in-cells are also used to estimate at 0.3 galaxy h-squared/Mpc the average galaxy surface density in sheets like the Great Wall.

  19. Ostreopsis cf. ovata dynamics in the NW Mediterranean Sea in relation to biotic and abiotic factors.

    PubMed

    Carnicer, Olga; Guallar, Carles; Andree, Karl B; Diogène, Jorge; Fernández-Tejedor, Margarita

    2015-11-01

    An expansion of the distribution of Ostreopsis cf. ovata, a dinoflagellate which produces palytoxin-like compounds, has been reported in recent years. Economical and social interests are affected by blooms, as they are responsible for respiratory and skin problems in humans and may cause damage to marine organisms. In order to identify the most influential environmental factors that trigger proliferations of O. cf. ovata in the area of the adjacent shallow rocky coast of the Ebro Delta (NW Mediterranean Sea) a three-year survey was performed on the metaphytic microalgae community growing on the macrophytes Jania rubens and Corallina elongata. Small-size diatoms were more abundant than dinoflagellates; O. cf. ovata was identified as the only species present from the genus. Seawater temperature was the primary driver defining the ecological niche of O. cf. ovata. Freshwater and groundwater fluxes were more pronounced in southern than in northern sites, which may have resulted in a distinct O. cf. ovata spatial distribution, with the highest records of abundance and more frequent blooms in the north. In consequence, negative correlations between the abundance of O. cf. ovata and nitrate concentrations and significant positive correlation with salinity were observed. The temporal pattern of O. cf. ovata dynamics from mid-July to early-November is probably due to the fact that this species is observed only above a certain threshold temperature of seawater. Metaphytic cells of O. cf. ovata were smaller in the northern site than in the south, possibly as a result of an increase in cell division, coinciding with higher abundance, and this could be an indicator of favorable conditions. Toxicity in planktonic cells was negatively correlated with cell abundance in the water column, achieving maximum concentrations of 25pg. PLTX eqcell(-1). Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Microstructure and Mechanical Property of SiCf/SiC and Cf/SiC Composites

    NASA Astrophysics Data System (ADS)

    Lee, S. P.; Cho, K. S.; Lee, H. U.; Lee, J. K.; Bae, D. S.; Byun, J. H.

    2011-10-01

    The mechanical properties of SiC based composites reinforced with different types of fabrics have been investigated, in conjunction with the detailed analyses of their microstructures. The thermal shock properties of SiCf/SiC composites were also examined. All composites showed a dense morphology in the matrix region. Carbon coated PW-SiCf/SiC composites had a good fracture energy, even if their strength was lower than that of PW-Cf/SiC composites. SiCf/SiC composites represented a great reduction of flexural strength at the thermal shock temperature difference of 300 °C.

  1. [Stem cells in adults].

    PubMed

    Borge, O J; Funderud, S

    2001-08-30

    We present a literature review of the plasticity observed by adult stem cells. We have reviewed the literature regarding stem cells from adults in order to summarise their ability to generate cells of other types than those of the tissue/organ from which they were isolated. Adult stem cells have recently been demonstrated to terminally differentiate into cells of other tissues than those from which they were originally isolated. For example, bone marrow cells have been shown to generate liver, nerve, heart and skeletal muscle cells in addition to their well-known ability to produce blood and mesenchymal cells. Most studies demonstrate a proof-of-principle in animal models; much more research is needed before adult stem cells can be utilised in human medicine. However, the published reports are encouraging and give reasons for a cautious optimism with regard to future clinical use.

  2. Positive pressure--analysing the effect of the addition of non-invasive ventilation (NIV) to home airway clearance techniques (ACT) in adult cystic fibrosis (CF) patients.

    PubMed

    Stanford, Gemma; Parrott, Helen; Bilton, Diana; Agent, Penny

    2015-05-01

    There is no published literature on the frequency of use of non-invasive ventilation (NIV) with airway clearance techniques (ACT) throughout the cystic fibrosis (CF) population; 3.9% (191 people of 5062 registered) of the United Kingdom CF population older than 16 years are reported to use NIV in registry data; however, it is not specified if this is for ACT or respiratory failure. Using NIV with ACT decreases work of breathing and fatigue during in-patient admissions for CF patients. We hypothesised these effects could be replicated at home, potentially reducing hospital admissions. Fourteen adult patients with CF scored ease of clearance and breathlessness with ACT before and after addition of NIV to normal ACT routine using a visual analog scale. Patient views on NIV with ACT were collected via a structured interview. Number of home intravenous (IV) antibiotic courses and days in hospital was collected for one year pre- and post-NIV provision. Patients reported statistically significant improvements in ease of clearance (p = 0.011) and reduced breathlessness during ACT using NIV (p = 0.011). Structured interview results indicated patient reports of sputum clearance improved. In-patient days were lower, while home IV days were higher after NIV was set up, although not statistically significant. This study is limited by small numbers; however, trends towards less hospital admissions and greater patient ease while using NIV with ACT warrant further investigation.

  3. Adult T-Cell Leukemia/Lymphoma

    MedlinePlus

    ... Adult T-Cell Leukemia/Lymphoma Adult T-Cell Leukemia/Lymphoma Adult T-cell A type of white ... immune responses by destroying harmful substances or cells. leukemia Disease generally characterized by the overproduction of abnormal ...

  4. Gladstone-Dale constant for CF4. [experimental design

    NASA Technical Reports Server (NTRS)

    Burner, A. W., Jr.; Goad, W. K.

    1980-01-01

    The Gladstone-Dale constant, which relates the refractive index to density, was measured for CF4 by counting fringes of a two-beam interferometer, one beam of which passes through a cell containing the test gas. The experimental approach and sources of systematic and imprecision errors are discussed. The constant for CF4 was measured at several wavelengths in the visible region of the spectrum. A value of 0.122 cu cm/g with an uncertainty of plus or minus 0.001 cu cm/g was determined for use in the visible region. A procedure for noting the departure of the gas density from the ideal-gas law is discussed.

  5. Assessing disease disclosure in adults with cystic fibrosis: the Adult Data for Understanding Lifestyle and Transitions (ADULT) survey Disclosure of disease in adults with cystic fibrosis

    PubMed Central

    2010-01-01

    Background As more patients with cystic fibrosis (CF) reach adulthood and participate in age-appropriate activities (e.g. employment, dating), disclosure of medical status becomes more important. This study assessed rates of disclosure and its perceived impact on relationships using the Adult Data for Understanding Lifestyle and Transitions (ADULT) online survey. Methods Adults with CF participated in the survey via the United States national network of CF Centers. Descriptive and inferential statistics were utilized. Results Participants (n = 865) were more likely to disclose to relatives (94%) and close friends (81%) than to dating partners (73%), bosses/supervisors/teachers (51%) or co-workers (39%). Respondents generally reported a neutral/positive effect on relationships following disclosure. Negative effects of disclosure were infrequent, but more likely with dating partners or bosses/supervisors/teachers. Results also indicated that disclosure may be influenced by severity of lung disease and gender, with those having normal/mild lung disease less likely to disclose their diagnosis to both co-workers (p < 0.01) and bosses/supervisors/teachers (p < 0.01), and women being more likely to disclose to close friends (p < 0.0001) and dating partners (p < 0.05) than men. Conclusions Most adults with CF disclosed their disease to relatives and close friends. Individuals with severe CF lung disease were more likely to disclose their diagnosis to coworkers and supervisors/teachers. It may be helpful to provide support for disclosure of disease in situations such as employment and dating. PMID:20831811

  6. Assessing disease disclosure in adults with cystic fibrosis: the Adult Data for Understanding Lifestyle and Transitions (ADULT) survey Disclosure of disease in adults with cystic fibrosis.

    PubMed

    Modi, Avani C; Quittner, Alexandra L; Boyle, Michael P

    2010-09-10

    As more patients with cystic fibrosis (CF) reach adulthood and participate in age-appropriate activities (e.g. employment, dating), disclosure of medical status becomes more important. This study assessed rates of disclosure and its perceived impact on relationships using the Adult Data for Understanding Lifestyle and Transitions (ADULT) online survey. Adults with CF participated in the survey via the United States national network of CF Centers. Descriptive and inferential statistics were utilized. Participants (n = 865) were more likely to disclose to relatives (94%) and close friends (81%) than to dating partners (73%), bosses/supervisors/teachers (51%) or co-workers (39%). Respondents generally reported a neutral/positive effect on relationships following disclosure. Negative effects of disclosure were infrequent, but more likely with dating partners or bosses/supervisors/teachers. Results also indicated that disclosure may be influenced by severity of lung disease and gender, with those having normal/mild lung disease less likely to disclose their diagnosis to both co-workers (p < 0.01) and bosses/supervisors/teachers (p < 0.01), and women being more likely to disclose to close friends (p < 0.0001) and dating partners (p < 0.05) than men. Most adults with CF disclosed their disease to relatives and close friends. Individuals with severe CF lung disease were more likely to disclose their diagnosis to coworkers and supervisors/teachers. It may be helpful to provide support for disclosure of disease in situations such as employment and dating.

  7. First record of Ianiropsis cf. serricaudis in Maryland Coastal Bays, USA (Crustacea, Peracarida, Janiridae)

    PubMed Central

    Morales-Núñez, Andrés G; Chigbu, Paulinus

    2018-01-01

    Abstract During monthly sampling of benthic invertebrates at 13 stations in the Maryland Coastal Bays (MCBs) from March to December 2012, a total of 29 individuals of Ianiropsis cf. serricaudis were collected. This species is being reported for the first time in MCBs. A detailed illustration and description of an adult male of I. cf. serricaudis from MCBs is presented. An illustrated key of males of Ianiropsis species belonging to the palpalis-group is also presented. The size of the largest male was 3.0 mm and that of the largest female was 2.5 mm. It is possible that I. cf. serricaudis was present in the MCBs, but overlooked during previous surveys of marine benthic invertebrates in the area because of its small body size and lack of taxonomic expertise. PMID:29674907

  8. On reaction kinetics and atmospheric lifetimes of CF3CFHCF3 and CF3CH2Br

    NASA Technical Reports Server (NTRS)

    Nelson, D. D., Jr.; Zahniser, M. S.; Kolb, C. E.

    1993-01-01

    The rate constants for the reaction of the OH radical with CF3CFHCF3 and with CF3CH2Br have been measured as a function of temperature using the discharge flow technique with laser induced fluorescence detection of the OH radicals. The temperature dependent rate coefficients are well described by a simple Arrhenius expression, k(T) = A exp(E/(RT)). For the reaction of OH with CF3CFHCF3 we find A = 3.7 x 10 exp -13 cu cm/molecules/s and E/R = 1615 K; for the reaction of OH with CF3CH2Br we report A = 1.4 x 10 exp -12 cu cm/molecule/s and E/R = 1350 K. These Arrhenius parameters imply rate coefficients at 277 K of 1.09 x 10 exp -15 cu cm/molecule/s for CF3CFHCF3 and 1.06 x 10 exp -14 cu cm/molecule/s for CF3CH2Br. We find atmospheric lifetimes for CF3CFHCH3 and CF3CH2Br of 42 years and 4.1 years, respectively. We also estimate the steady state ozone depletion potential (ODP) of the brominated species relative to CFCl3 as about 0.84 using a semiempirical model.

  9. 76 FR 14796 - Airworthiness Directives; General Electric Company CF6-45 and CF6-50 Series Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-18

    ... Airworthiness Directives; General Electric Company CF6-45 and CF6-50 Series Turbofan Engines AGENCY: Federal... airworthiness directive (AD) for General Electric Company (GE) CF6-45 and CF6-50 series turbofan engines. That..., and MD-10- 30F. The commenter stated that the proposed AD only listed these airplanes as a series. We...

  10. 76 FR 292 - Airworthiness Directives; General Electric Company CF6-45 and CF6-50 Series Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    [email protected]ge.com . You may review copies of the referenced service information at the FAA, Engine..., February 26, 2009), for GE CF6-45 and CF6-50 series turbofan engines. That AD requires replacing LFCEN... that this proposed AD would affect 383 GE CF6-45 and CF6-50 series turbofan engines installed on...

  11. LEM-CF Premixed Tool Kit

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

    2015-01-19

    The purpose of LEM-CF Premixed Tool Kit is to process premixed flame simulation data from the LEM-CF solver (https://fileshare.craft-tech.com/clusters/view/lem-cf) into a large-eddy simulation (LES) subgrid model database. These databases may be used with a user-defined-function (UDF) that is included in the Tool Kit. The subgrid model UDF may be used with the ANSYS FLUENT flow solver or other commercial flow solvers.

  12. Forming trifluoromethylmetallates: competition between decarboxylation and C-F bond activation of group 11 trifluoroacetate complexes, [CF3CO2ML]-.

    PubMed

    Rijs, Nicole J; O'Hair, Richard A J

    2012-03-28

    A combination of gas-phase 3D quadrupole ion trap mass spectrometry experiments and density functional theory (DFT) calculations have been used to examine the mechanism of thermal decomposition of fluorinated coinage metal carboxylates. The precursor anions, [CF(3)CO(2)MO(2)CCF(3)](-) (M = Cu, Ag and Au), were introduced into the gas-phase via electrospray ionization. Multistage mass spectrometry (MS(n)) experiments were conducted utilizing collision-induced dissociation, yielding a series of trifluoromethylated organometallic species and fluorides via the loss of CO(2), CF(2) or "CF(2)CO(2)". Carboxylate ligand loss was insignificant or absent in all cases. DFT calculations were carried out on a range of potentially competing fragmentation pathways for [CF(3)CO(2)MO(2)CCF(3)](-), [CF(3)CO(2)MCF(3)](-) and [CF(3)CO(2)MF](-). These shed light on possible products and mechanisms for loss of "CF(2)CO(2)", namely, concerted or step-wise loss of CO(2) and CF(2) and a CF(2)CO(2) lactone pathway. The lactone pathway was found to be higher in energy in all cases. In addition, the possibility of forming [CF(3)MCF(3)](-) and [CF(3)MF](-), via decarboxylation is discussed. For the first time the novel fluoride complexes [FMF](-), M = Cu, Ag and Au have been experimentally observed. Finally, the decomposition reactions of [CF(3)CO(2)ML](-) (where L = CF(3) and CF(3)CO(2)) and [CH(3)CO(2)ML](-) (where L = CH(3) and CH(3)CO(2)) are compared.

  13. In situ CF3 Detection in Low Pressure Inductive Discharges by Fourier Transform Infrared Spectroscopy

    NASA Technical Reports Server (NTRS)

    Kim, J. S.; Cappelli, M. A.; Sharma, S. P.; Arnold, J. O. (Technical Monitor)

    1998-01-01

    The detection of CF(x) (x=1-3) radicals in low pressure discharges using source gases such as CF4 and CHF3 is of importance to the understanding of their chemical structure and relevance in plasma based etching processes. These radicals are known to contribute to the formation of fluorocarbon polymer films, which affect the selectivity and anisotropy of etching. In this study, we present preliminary results of the quantitative measurement of trifluoromethyl radicals, CF3, in low pressure discharges. The discharge studied here is an inductively (transformer) coupled plasma (ICP) source in the GEC reference cell, operating on pure CF4 at pressures ranging from 10 - 100 mTorr, This plasma source generates higher electron number densities at lower operating pressures than obtainable with the parallel-plate capacitively coupled version of the GEC reference cell. Also, this expanded operating regime is more relevant to new generations of industrial plasma reactors being used by the microelectronics industry. Fourier transform infrared (FTIR) spectroscopy is employed to observe the absorption band of CF3 radicals in the electronic ground state X2Al in the region of 1233-1270/cm. The spectrometer is equipped with a high sensitivity HgCdTe (MCT) detector and has a fixed resolution of 0.125/cm. The CF3 concentrations are measured for a range of operating pressures and discharge power levels.

  14. Dating groundwater with trifluoromethyl sulfurpentafluoride (SF 5CF3), sulfur hexafluoride (SF6), CF 3Cl (CFC-13), and CF2Cl2 (CFC-12)

    USGS Publications Warehouse

    Busenberg, E.; Plummer, Niel

    2008-01-01

    [1] A new groundwater dating procedure using the transient atmospheric signal of the environmental tracers SF5CF3, CFC-13, SF6, and CFC-12 was developed. The analytical procedure determines concentrations of the four tracers in air and water samples. SF 5CF3 and CFC-13 can be used to date groundwaters in some environments where the CFCs and SF6 have previously failed because these new tracers have increasing atmospheric input functions, no known terrigenic source, and are believed to be stable under reducing conditions. SF5CF3 has a dating range from 1970 to modern; the mixing ratio (mole fraction) in North American air has increased from the detection limit of 0.005 parts per trillion (ppt) to the 2006 mole fraction of about 0.16 ppt. No evidence was found for degradation of SF5CF3 in laboratory anaerobic systems. The solubility of SF5CF3 was measured in water from 1 to 35??C. Groundwater samples that contained large amounts of terrigenic SF6 did not contain terrigenic SF 5CF3. CFC-13 is a trace atmospheric gas with a dating range in groundwater of about 1965 to modem. CFC-13 has been used primarily in very low-temperature refrigeration; thus groundwater environments are less likely to be contaminated with nonatmospheric sources as compared to other widely used CFCs. Because of the low solubility of SF5CF3 and CFC-13 in water, an excess air correction must be applied to the apparent ages. The new dating procedure was tested in water samples from wells and springs from Maryland, Virginia, and West Virginia.

  15. Cell Phone Intervention to Improve Adherence

    PubMed Central

    Marciel, Kristen K.; Saiman, Lisa; Quittell, Lynne M.; Dawkins, Kevin; Quittner, Alexandra L.

    2010-01-01

    Summary Background Treatment regimens for patients with cystic fibrosis (CF) are time-consuming and complex, resulting in consistently low adherence rates. To date, few studies have evaluated innovative technologies to improve adherence in this population. Current infection control guidelines for patients with CF seek to minimize patient-to-patient transmission of potential pathogens. Thus, interventions must avoid face-to-face contact and be delivered individually, limiting opportunities for peer support. This study aimed to develop and assess a web-enabled cell phone, CFFONE™, designed to provide CF information and social support to improve adherence in adolescents with CF. Methods The acceptability, feasibility, and utility of CFFONE™ were evaluated with health care professionals (n = 17) adolescents with CF aged 11–18 years old (n = 12), adults with CF aged 21–36 years old (n = 6), parents of adolescents with CF (n = 12), and technology experts (n = 8). Adolescents also tested a prototype of CFFONE™ (n = 9). Qualitative and quantitative data were collected. Results Focus group data with health care = professionals indicated a need for this intervention, and indicated that CFFONE™ would be likely to improve knowledge and social support, and somewhat likely to improve adherence. Adolescent, adults, and parents all rated CFFONE™ as likely to improve adherence. Technology experts rated the prototype design and format as appropriate. Conclusions The current study provided some support from key stakeholders for this intervention to improve adherence in adolescents with CF. Next steps include a multi-center trial of the efficacy and safety of CFFONE™. PMID:20054860

  16. Induction of an antiinflammatory effect and prevention of cartilage damage in rat knee osteoarthritis by CF101 treatment.

    PubMed

    Bar-Yehuda, S; Rath-Wolfson, L; Del Valle, L; Ochaion, A; Cohen, S; Patoka, R; Zozulya, G; Barer, F; Atar, E; Piña-Oviedo, S; Perez-Liz, G; Castel, D; Fishman, P

    2009-10-01

    Studies have suggested that rheumatoid arthritis (RA) and osteoarthritis (OA) share common characteristics. The highly selective A(3) adenosine receptor agonist CF101 was recently defined as a potent antiinflammatory agent for the treatment of RA. The purpose of this study was to examine the effects of CF101 on the clinical and pathologic manifestations of OA in an experimental animal model. OA was induced in rats by monosodium iodoacetate, and upon disease onset, oral treatment with CF101 (100 microg/kg given twice daily) was initiated. The A(3) adenosine receptor antagonist MRS1220 (100 microg/kg given twice daily) was administered orally, 30 minutes before CF101 treatment. The OA clinical score was monitored by knee diameter measurements and by radiographic analyses. Histologic analyses were performed following staining with hematoxylin and eosin, Safranin O-fast green, or toluidine blue, and histologic changes were scored according to a modified Mankin system. Signaling proteins were assayed by Western blotting; apoptosis was detected via immunohistochemistry and TUNEL analyses. CF101 induced a marked decrease in knee diameter and improved the changes noted on radiographs. Administration of MRS1220 counteracted the effects of CF101. CF101 prevented cartilage damage, osteoclast/osteophyte formation, and bone destruction. In addition, CF101 markedly reduced pannus formation and lymphocyte infiltration. Mechanistically, CF101 induced deregulation of the NF-kappaB signaling pathway, resulting in down-regulation of tumor necrosis factor alpha. Consequently, CF101 induced apoptosis of inflammatory cells that had infiltrated the knee joints; however, it prevented apoptosis of chondrocytes. CF101 deregulated the NF-kappaB signaling pathway involved in the pathogenesis of OA. CF101 induced apoptosis of inflammatory cells and acted as a cartilage protective agent, which suggests that it would be a suitable candidate drug for the treatment of OA.

  17. Adherence and Recursive Perception Among Young Adults with Cystic Fibrosis.

    PubMed

    Oddleifson, D August; Sawicki, Gregory S

    2017-04-01

    Adherence to prescribed treatment is a pressing issue for adolescents and young adults with cystic fibrosis (CF). This paper presents two narratives from the thematic analysis of unstructured interviews with 14 adolescents, young adults, and older adults living with CF. Through a new identity-based framework termed recursive perception that draws focus on how an individual perceives how others view them, it explores the social context of adherence and self-care among young adults with CF. It demonstrates that an individual's understanding of self and desire to maintain a certain image for peers can be deeply embedded in adherence and self-care patterns, leading individuals to feel they need to choose between tending to their health needs and living their lives. This suggests that current biomedical innovation in CF care must be complemented with renewed efforts to find effective means to empower young adults with CF to successfully navigate the social challenges of their illness and avoid the pitfalls of nonadherence that can lead to a permanent worsening of their health condition.

  18. Diagnosis of Adult Patients with Cystic Fibrosis.

    PubMed

    Nick, Jerry A; Nichols, David P

    2016-03-01

    The diagnosis of cystic fibrosis (CF) is being made with increasing frequency in adults. Patients with CF diagnosed in adulthood typically present with respiratory complaints, and often have recurrent or chronic airway infection. At the time of initial presentation individuals may appear to have clinical manifestation limited to a single organ, but with subclinical involvement of the respiratory tract. Adult-diagnosed patients have a good response to CF center care, and newly available cystic fibrosis transmembrane receptor-modulating therapies are promising for the treatment of residual function mutation, thus increasing the importance of the diagnosis in adults with unexplained bronchiectasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Rate contants for CF{sub 3} + H{sub 2} {yields} CF{sub 3}H + H and CF{sub 3}H + H {yields} CF{sub 3} + H{sub 2} reactions in the temperature range 1100-1600 K.

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

    Hranisavljevic, J.; Michael, V.; Chemistry

    1998-09-24

    The shock tube technique coupled with H-atom atomic resonance absorption spectrometry has been used to study the reactions (1) CF{sub 3} + H{sub 2} {yields} CF{sub 3}H + H and (2) CF{sub 3}H + H{yields} CF{sub 3} + H{sub 2} over the temperature ranges 1168-1673 K and 1111-1550 K, respectively. The results can be represented by the Arrhenius expressions k1 = 2.56 x 10{sup -11} exp(-8549K/T) and k2 = 6.13 x 10{sup -11} exp(-7364K/T), both in cm3 molecule-1 s-1. Equilibrium constants were calculated from the two Arrhenius expressions in the overlapping temperature range, and good agreement was obtained with themore » literature values. The rate constants for reaction 2 were converted into rate constants for reaction 1 using literature equilibrium constants. These data are indistinguishable from direct k1 measurements, and an Arrhenius fit for the joint set is k{sub 1} = 1.88 x 10{sup -11} exp(-8185K/T) cm3 molecule-1 s-1. The CF{sub 3} + H{sub 2} {yields} CF{sub 3}H + H reaction was further modeled using conventional transition-state theory, which included ab initio electronic structure determinations of reactants, transition state, and products.« less

  20. Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance.

    PubMed

    Sheikh, Saba; Gudipaty, Lalitha; De Leon, Diva D; Hadjiliadis, Denis; Kubrak, Christina; Rosenfeld, Nora K; Nyirjesy, Sarah C; Peleckis, Amy J; Malik, Saloni; Stefanovski, Darko; Cuchel, Marina; Rubenstein, Ronald C; Kelly, Andrea; Rickels, Michael R

    2017-01-01

    Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined β-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced β-cell secretory capacity and α-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite "normal" glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF. © 2017 by the American Diabetes Association.

  1. The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures.

    PubMed

    Trieschmann, Jan; Bettin, Daniel; Haustein, Moritz; Köster, Annette; Molcanyi, Marek; Halbach, Marcel; Hanna, Mira; Fouad, Mariam; Brockmeier, Konrad; Hescheler, Jürgen; Pfannkuche, Kurt; Hannes, Tobias

    2016-01-01

    Transplantation of stem cell-derived cardiomyocytes is one of the most promising therapeutic approaches after myocardial infarction, as loss of cardiomyocytes is virtually irreversible by endogenous repair mechanisms. In myocardial scars, transplanted cardiomyocytes will be in immediate contact with cardiac fibroblasts. While it is well documented how the electrophysiology of neonatal cardiomyocytes is modulated by cardiac fibroblasts of the same developmental stage, it is unknown how adult cardiac fibroblasts (aCFs) affect the function of embryonic stem cell-derived cardiomyocytes (ESC-CMs). To investigate the effects of aCFs on ESC-CM electrophysiology, we performed extra- and intracellular recordings of murine aCF-ESC-CM cocultures. We observed that spontaneous beating behaviour was highly irregular in aCF-ESC-CM cocultures compared to cocultures with mesenchymal stem cells (coefficient of variation of the interspike interval: 40.5 ± 15.2% versus 9.3 ± 2.0%, p = 0.008) and that action potential amplitude and maximal upstroke velocity (V max) were reduced (amplitude: 52.3 ± 1.7 mV versus 65.1 ± 1.5 mV, V max: 7.0 ± 1.0 V/s versus 36.5 ± 5.3 V/s), while action potential duration (APD) was prolonged (APD50: 25.6 ± 1.0 ms versus 16.8 ± 1.9 ms, p < 0.001; APD90: 52.2 ± 1.5 ms versus 43.3 ± 3.3 ms, p < 0.01) compared to controls. Similar changes could be induced by aCF-conditioned medium. We conclude that the presence of aCFs changes automaticity and induces potentially proarrhythmic changes of ESC-CM electrophysiology.

  2. 76 FR 52215 - Airworthiness Directives; General Electric Company CF34-10E2A1; CF34-10E5; CF34-10E5A1; CF34-10E6...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-22

    ...; CF34-10E7; and CF34- 10E7-B Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... cracked at the attachment lugs. We are issuing this AD to prevent high-cycle fatigue cracking of the fan..., uncontained failure of the engine, and damage to the airplane. DATES: This AD is effective September 26, 2011...

  3. Cystic Fibrosis (CF) Respiratory Screen: Sputum

    MedlinePlus

    ... for Educators Search English Español Cystic Fibrosis (CF) Respiratory Screen: Sputum KidsHealth / For Parents / Cystic Fibrosis (CF) Respiratory Screen: Sputum What's in this article? What It ...

  4. A data model of the Climate and Forecast metadata conventions (CF-1.6) with a software implementation (cf-python v2.1)

    NASA Astrophysics Data System (ADS)

    Hassell, David; Gregory, Jonathan; Blower, Jon; Lawrence, Bryan N.; Taylor, Karl E.

    2017-12-01

    The CF (Climate and Forecast) metadata conventions are designed to promote the creation, processing, and sharing of climate and forecasting data using Network Common Data Form (netCDF) files and libraries. The CF conventions provide a description of the physical meaning of data and of their spatial and temporal properties, but they depend on the netCDF file encoding which can currently only be fully understood and interpreted by someone familiar with the rules and relationships specified in the conventions documentation. To aid in development of CF-compliant software and to capture with a minimal set of elements all of the information contained in the CF conventions, we propose a formal data model for CF which is independent of netCDF and describes all possible CF-compliant data. Because such data will often be analysed and visualised using software based on other data models, we compare our CF data model with the ISO 19123 coverage model, the Open Geospatial Consortium CF netCDF standard, and the Unidata Common Data Model. To demonstrate that this CF data model can in fact be implemented, we present cf-python, a Python software library that conforms to the model and can manipulate any CF-compliant dataset.

  5. Parenting adolescents with cystic fibrosis: the adolescents' and young adults' perspectives.

    PubMed

    Bregnballe, Vibeke; Schiøtz, Peter Oluf; Lomborg, Kirsten

    2011-01-01

    When suffering from cystic fibrosis (CF), a number of problems may arise during adolescence; for example, poor adherence. The problems may be attributed to the adolescent being insufficiently prepared for adult life. Research on different ways of parenting adolescents with CF and the influence of different parenting styles on the adolescents' adherence to treatment is still limited. The aim of this study was to identify the types of parental support that adolescents and young adults with CF want and find helpful in terms of preparing them for adult life. Sixteen Danish adolescents with CF, aged 14-25, participated in the study. Two focus group interviews were carried out, one for 14-18-year-olds and one for 19-25-year-olds. Individual interviews were conducted, with three subjects. Using interpretive description strategy, a secondary analysis of the interview data was conducted. The adolescents and young adults wanted their parents educated about the adolescent experience. They wanted their parents to learn a pedagogical parenting style, to learn to trust them, and to learn to gradually transfer responsibility for their medical treatment. Additionally, the adolescents noted that meeting other parents may be beneficial for the parents. The findings of this study suggest that adolescents and young adults with CF want their parents to be educated about how to handle adolescents with CF and thereby sufficiently prepare them for adult life.

  6. The psychometric properties of the Leicester Cough Questionnaire and Respiratory Symptoms in CF tool in cystic fibrosis: A preliminary study.

    PubMed

    Ward, Nathan; Stiller, Kathy; Rowe, Hilary; Holland, Anne E

    2017-05-01

    There are few tools to quantify the impact of cough in cystic fibrosis (CF). The psychometric properties of the Leicester Cough Questionnaire (LCQ) and Respiratory Symptoms in CF (ReS-CF) tool were investigated in adults with CF. Validity and reliability were assessed in clinically stable participants who completed the questionnaires twice, along with the Cystic Fibrosis Questionnaire - Revised (CFQ-R). Responsiveness was assessed by change in questionnaires following treatment for an acute respiratory exacerbation. Correlations between the LCQ and CFQ-R respiratory domain were moderate (n=59, r s =0.78, p<0.001). Correlations between ReS-CF and CFQ-R respiratory domain were fair (r s =-0.50, p<0.001). The LCQ total score was repeatable (ICC 0.92, 95%CI 0.87-0.96, n=50). In those reporting improvement in symptoms following treatment (n=36), LCQ total score had a mean change of 4.6 (SD 3.7) and effect size of 1.2. The LCQ and ReS-CF appear to be valid, reliable and responsive in CF. www.anzctr.org.au: ACTRN12615000262505. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  7. Clinical grade adult stem cell banking

    PubMed Central

    Thirumala, Sreedhar; Goebel, W Scott

    2009-01-01

    There has been a great deal of scientific interest recently generated by the potential therapeutic applications of adult stem cells in human care but there are several challenges regarding quality and safety in clinical applications and a number of these challenges relate to the processing and banking of these cells ex-vivo. As the number of clinical trials and the variety of adult cells used in regenerative therapy increases, safety remains a primary concern. This has inspired many nations to formulate guidelines and standards for the quality of stem cell collection, processing, testing, banking, packaging and distribution. Clinically applicable cryopreservation and banking of adult stem cells offers unique opportunities to advance the potential uses and widespread implementation of these cells in clinical applications. Most current cryopreservation protocols include animal serum proteins and potentially toxic cryoprotectant additives (CPAs) that prevent direct use of these cells in human therapeutic applications. Long term cryopreservation of adult stem cells under good manufacturing conditions using animal product free solutions is critical to the widespread clinical implementation of ex-vivo adult stem cell therapies. Furthermore, to avoid any potential cryoprotectant related complications, reduced CPA concentrations and efficient post-thaw washing to remove CPA are also desirable. The present review focuses on the current strategies and important aspects of adult stem cell banking for clinical applications. These include current good manufacturing practices (cGMPs), animal protein free freezing solutions, cryoprotectants, freezing & thawing protocols, viability assays, packaging and distribution. The importance and benefits of banking clinical grade adult stem cells are also discussed. PMID:20046678

  8. Coffee mitigates cyclophosphamide-induced genotoxic damage in Drosophila melanogaster germ cells.

    PubMed

    Nagpal, Isha; Abraham, Suresh K

    2018-02-26

    In the present study, coffee (CF) was evaluated for its protective effects against genotoxic damage and oxidative stress induced by the chemotherapeutic drug, cyclophosphamide (CPH). The sex-linked recessive lethal (SLRL) test was employed to study the induction of mutations in the larvae as well as in all the successive germ cell stages of treated males. Control and treated third instar larvae were used to monitor the biomarkers of oxidative stress response such as glutathione content (GSH), glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD) and lipid peroxidation (MDA content). Our results demonstrated that co-administration of CF (2%) with CPH (3 mM) has significantly reduced CPH-induced lethal mutations in the germ cells of larvae and adult flies. The reductions observed in mutation frequencies were: 75% in larvae and 62.4% in the adult. Significant enhancement in antioxidant enzymatic levels: CAT (46.6%) > SOD (43.0%) > GST (42.4%) > GSH (31.6%) and reduction in MDA levels (32.05%) in the pretreated third instar larvae demonstrated the antioxidant activity of CF against CPH-induced oxidative stress. The findings from the present study suggest that the Drosophila model is an ideal one for evaluating the antigenotoxic and antioxidant activity of complex mixtures like CF.

  9. Cross sections for elastic scattering of electrons by CF3Cl, CF2Cl2, and CFCl3

    NASA Astrophysics Data System (ADS)

    Hoshino, M.; Horie, M.; Kato, H.; Blanco, F.; García, G.; Limão-Vieira, P.; Sullivan, J. P.; Brunger, M. J.; Tanaka, H.

    2013-06-01

    Differential, integral, and momentum transfer cross sections have been determined for the elastic scattering of electrons from the molecules CF3Cl, CF2Cl2, and CFCl3.With the help of a crossed electron beam-molecular beam apparatus using the relative flow technique, the ratios of the elastic differential cross sections (DCSs) of CF3Cl, CF2Cl2, and CFCl3 to those of He were measured in the energy region from 1.5 to 100 eV and at scattering angles in the range 15° to 130°. From those ratios, the absolute DCSs were determined by utilizing the known DCS of He. For CF3Cl and CF2Cl2, at the common energies of measurement, we find generally good agreement with the results from the independent experiments of Mann and Linder [J. Phys. B 25, 1621 (1992), 10.1088/0953-4075/25/7/030; Mann and Linder J. Phys. B 25, 1633 (1992), 10.1088/0953-4075/25/7/031]. In addition, as a result of progressively substituting a Cl-atom, undulations in the angular distributions have been found to vary in a largely systematic manner in going from CF4 to CF3Cl to CF2Cl2 to CFCl3 and to CCl4. These observed features suggest that the elastic scattering process is, in an independently additive manner, dominated by the atomic-Cl atoms of the molecules. The present independent atom method calculation typically supports the experimental evidence, within the screened additivity rule formulation, for each species and for energies greater than about 10-20 eV. Integral elastic and momentum transfer cross sections were also derived from the measured DCSs, and are compared to the other available theoretical and experimental results. The elastic integral cross sections are also evaluated as a part of their contribution to the total cross section.

  10. Thermodynamic properties of seven gaseous halogenated hydrocarbons from acoustic measurements: CHClFCF{sub 3}, CHF{sub 2}CF{sub 3}, CF{sub 3}CH{sub 3}, CHF{sub 2}CH{sub 3}, CF{sub 3}CHFCHF{sub 2},CF{sub 3}CH{sub 2}CF{sub 3}, and CHF{sub 2}CF{sub 2}CH{sub 2}F

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

    Gillis, K.A.

    1997-01-01

    Measurements of the speed of sound in seven halogenated hydrocarbons are presented. The compounds in this study are 1-chloro-,2,2,2-tetrafluoroethane (CHCIFCF{sub 3} or HCFC-124), pentafluoroethane (CHF{sub 2}CF{sub 3} or HFC-125), 1,1,1-trifluoroethane (CF{sub 3}CH{sub 3} or HFC-143a), 1,1-difluoroethane (CHF{sub 2}CH{sub 3} or HFC-152a), 1,1,2,3,3-hexafluoropropane (CF{sub 3}CHFCHF{sub 2} or HFC-236ea), 1,1,1,3,3,3-hexafluoropropane (CF{sub 3}CH{sub 2}CF{sub 3} or HFC-236fa), and 1,1,2,2,3-pentafluoropropane (CHF{sub 2}CF{sub 2}CH{sub 2}F or HFC-245ca). The measurements were performed with a cylindrical resonator at temperatures between 240 and 400 K and at pressures up to 1.0 MPa. Ideal-gas heat capacities and acoustic virial coefficients were directly deduced from the data. The ideal-gas heatmore » capacity of HFC-125 from this work differs from spectroscopic calculations by less than 0.2% over the measurement range. The coefficients for virial equations of state were obtained from the acoustic data and hard-core square-well intermolecular potentials. Gas densities that were calculated from the virial equations of state for HCFC-124 and HFC-125 differ from independent density measurements by at most 0.15%, for the ranges of temperature and pressure over which both acoustic and Burnett data exist. The uncertainties in the derived properties of the other five compounds are comparable to those for HCFC-124 and HFC-125.« less

  11. The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures

    PubMed Central

    Trieschmann, Jan; Bettin, Daniel; Haustein, Moritz; Köster, Annette; Molcanyi, Marek; Halbach, Marcel; Hanna, Mira; Fouad, Mariam; Brockmeier, Konrad; Hescheler, Jürgen; Pfannkuche, Kurt; Hannes, Tobias

    2016-01-01

    Transplantation of stem cell-derived cardiomyocytes is one of the most promising therapeutic approaches after myocardial infarction, as loss of cardiomyocytes is virtually irreversible by endogenous repair mechanisms. In myocardial scars, transplanted cardiomyocytes will be in immediate contact with cardiac fibroblasts. While it is well documented how the electrophysiology of neonatal cardiomyocytes is modulated by cardiac fibroblasts of the same developmental stage, it is unknown how adult cardiac fibroblasts (aCFs) affect the function of embryonic stem cell-derived cardiomyocytes (ESC-CMs). To investigate the effects of aCFs on ESC-CM electrophysiology, we performed extra- and intracellular recordings of murine aCF-ESC-CM cocultures. We observed that spontaneous beating behaviour was highly irregular in aCF-ESC-CM cocultures compared to cocultures with mesenchymal stem cells (coefficient of variation of the interspike interval: 40.5 ± 15.2% versus 9.3 ± 2.0%, p = 0.008) and that action potential amplitude and maximal upstroke velocity (V max) were reduced (amplitude: 52.3 ± 1.7 mV versus 65.1 ± 1.5 mV, V max: 7.0 ± 1.0 V/s versus 36.5 ± 5.3 V/s), while action potential duration (APD) was prolonged (APD50: 25.6 ± 1.0 ms versus 16.8 ± 1.9 ms, p < 0.001; APD90: 52.2 ± 1.5 ms versus 43.3 ± 3.3 ms, p < 0.01) compared to controls. Similar changes could be induced by aCF-conditioned medium. We conclude that the presence of aCFs changes automaticity and induces potentially proarrhythmic changes of ESC-CM electrophysiology. PMID:26880949

  12. A Monte Carlo Sensitivity Analysis of CF2 and CF Radical Densities in a c-C4F8 Plasma

    NASA Technical Reports Server (NTRS)

    Bose, Deepak; Rauf, Shahid; Hash, D. B.; Govindan, T. R.; Meyyappan, M.

    2004-01-01

    A Monte Carlo sensitivity analysis is used to build a plasma chemistry model for octacyclofluorobutane (c-C4F8) which is commonly used in dielectric etch. Experimental data are used both quantitatively and quantitatively to analyze the gas phase and gas surface reactions for neutral radical chemistry. The sensitivity data of the resulting model identifies a few critical gas phase and surface aided reactions that account for most of the uncertainty in the CF2 and CF radical densities. Electron impact dissociation of small radicals (CF2 and CF) and their surface recombination reactions are found to be the rate-limiting steps in the neutral radical chemistry. The relative rates for these electron impact dissociation and surface recombination reactions are also suggested. The resulting mechanism is able to explain the measurements of CF2 and CF densities available in the literature and also their hollow spatial density profiles.

  13. Rate constants for CF{sub 3} + H{sub 2} {r_arrow} CF{sub 3}H + H and CF{sub 3}H + H {r_arrow} CF{sub 3} + H{sub 2} reactions in the temperature range 1100--1600 K

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

    Hranisavljevic, J.; Michael, J.V.

    1998-09-24

    The shock tube technique coupled with H-atom atomic resonance absorption spectrometry has been used to study the reactions (1) CF{sub 3} + H{sub 2} {r_arrow} CF{sub 3}H + H and (2) CF{sub 3}H + H {r_arrow} CF{sub 3} + H{sub 2} over the temperature ranges 1168--1673 K and 1111--1550 K, respectively. The results can be represented by the Arrhenius expressions k{sub 1} = 2.56 {times} 10{sup {minus}11} exp({minus}8549K/T) and k{sub 2} = 6.13 {times} 10{sup {minus}11} exp({minus}7364K/T), both in cm{sup 3} molecule{sup {minus}1} s{sup {minus}1}. Equilibrium constants were calculated from the two Arrhenius expressions in the overlapping temperature range, andmore » good agreement was obtained with the literature values. The rate constants for reaction 2 were converted into rate constants for reaction 1 using literature equilibrium constants. These data are indistinguishable from direct k{sub 1} measurements, and an Arrhenius fit for the joint set is k{sub 1} = 1.88 {times} 10{sup {minus}11} exp({minus}8185K/T) cm{sup 3} molecule{sup {minus}1} s{sup {minus}1}. The CF{sub 3} + H{sub 2} {r_arrow} CF{sub 3}H + H reaction was further modeled using conventional transition-state theory, which included ab initio electronic structure determinations of reactants, transition state, and products.« less

  14. Pathogenesis, imaging and clinical characteristics of CF and non-CF bronchiectasis.

    PubMed

    Schäfer, Jürgen; Griese, Matthias; Chandrasekaran, Ravishankar; Chotirmall, Sanjay H; Hartl, Dominik

    2018-05-22

    Bronchiectasis is a common feature of severe inherited and acquired pulmonary disease conditions. Among inherited diseases, cystic fibrosis (CF) is the major disorder associated with bronchiectasis, while acquired conditions frequently featuring bronchiectasis include post-infective bronchiectasis and chronic obstructive pulmonary disease (COPD). Mechanistically, bronchiectasis is driven by a complex interplay of inflammation and infection with neutrophilic inflammation playing a predominant role. The clinical characterization and management of bronchiectasis should involve a precise diagnostic workup, tailored therapeutic strategies and pulmonary imaging that has become an essential tool for the diagnosis and follow-up of bronchiectasis. Prospective future studies are required to optimize the diagnostic and therapeutic management of bronchiectasis, particularly in heterogeneous non-CF bronchiectasis populations.

  15. Representing Simple Geometry Types in NetCDF-CF

    NASA Astrophysics Data System (ADS)

    Blodgett, D. L.; Koziol, B. W.; Whiteaker, T. L.; Simons, R.

    2016-12-01

    The Climate and Forecast (CF) metadata convention is well-suited for representing gridded and point-based observational datasets. However, CF currently has no accepted mechanism for representing simple geometry types such as lines and polygons. Lack of support for simple geometries within CF has unintentionally excluded a broad set of geoscientific data types from NetCDF-CF data encodings. For example, hydrologic datasets often contain polygon watershed catchments and polyline stream reaches in addition to point sampling stations and water management infrastructure. The latter has an associated CF specification. In the interest of supporting all simple geometry types within CF, a working group was formed following an EarthCube workshop on Advancing NetCDF-CF [1] to draft a CF specification for simple geometries: points, lines, polygons, and their associated multi-geometry representations [2]. The draft also includes parametric geometry types such as circles and ellipses. This presentation will provide an overview of the scope and content of the proposed specification focusing on mechanisms for representing coordinate arrays using variable length or continuous ragged arrays, capturing multi-geometries, and accounting for type-specific geometry artifacts such as polygon holes/interiors, node ordering, etc. The concepts contained in the specification proposal will be described with a use case representing streamflow in rivers and evapotranspiration from HUC12 watersheds. We will also introduce Python and R reference implementations developed alongside the technical specification. These in-development, open source Python and R libraries convert between commonly used GIS software objects (i.e. GEOS-based primitives) and their associated simple geometry CF representation. [1] http://www.unidata.ucar.edu/events/2016CFWorkshop/[2] https://github.com/bekozi/netCDF-CF-simple-geometry

  16. Study of the formation of interstellar CF+ from the HF + C + →CF+ + H reaction

    NASA Astrophysics Data System (ADS)

    Denis-Alpizar, Otoniel; Guzmán, Viviana V.; Inostroza, Natalia

    2018-06-01

    The detection of the carbon monofluoride cation CF+ was considered as a support of the theories of the fluorine chemistry in the interstellar medium (ISM). This molecule is formed by the reaction of HF with C+. The rates of this reaction have been estimated previously by two different groups. However, these two estimations led to different results. The main goal of the present work is to study the HF + C+ reaction and determine new reactive rate coefficients. A large set of ab initio energies at the MRCI-F12/cc-pVQZ-F12 level was computed. The first reactive potential energy surface (PES) for the HF + C+ → CF+ + H reaction was developed using a reproducing kernel Hilbert space (RKHS) based method. The dynamics of the reaction was followed from quasiclassical trajectories (QCT). The results of such calculations showed that CF+ is produced in excited vibrational states. The rate coefficients for the HF + C+ → CF+ + H reaction from 50 K up to 2000 K are reported. The impact of these new data in the astrophysical models for the determination of the interstellar conditions is also explored.

  17. Boltzmann Calculations of Electron Transport in CF4 and CF_4/Ar

    NASA Astrophysics Data System (ADS)

    Wang, Yicheng; van Brunt, R. J.

    1996-10-01

    A new set of electron collisional cross sections(L. G. Christophorou, J. K. Olthoff, and M. V. V. S. Rao, J. Phys. Chem. Ref. Data, submitted (May 1996)) for CF4 has been proposed, based primarily upon available experimental measurements. In this paper we present the results of calculations of the drift velocity, ionization coefficient, and attachment coefficient for electrons in CF4 based upon the new cross section set, using a two-term Boltzmann calculation. Comparison of results with experimental determinations of the transport parameters, such as drift velocity, are presented, along with comparison of results obtained using two previously pubished(M. Hyashi, in Swarm Studies and Elastic Electron-Molecule Collisions) (1987); and Y. Nakamura in Gaseous Electronics and Their Applications (1991) electron impact cross section sets for CF_4. Additions and adjustments to the cross section sets required for the model to achieve consitency with transport data are discussed. - Research sponsored in part by the U.S. Air Force Wright Laboratory under contract F33615-96-C-2600 with the University of Tennessee. Also, Department of Physics, The University of Tennessee, Knoxville, TN.

  18. Engine diagnostics program: CF6-50 engine performance deterioration

    NASA Technical Reports Server (NTRS)

    Wulf, R. H.

    1980-01-01

    Cockpit cruise recordings and test cell data in conjunction with hardware inspection results from airline overhaul shops were analyzed to define the extent and magnitude of performance deterioration of the General Electric CF6-50 high bypass turbofan engine. The magnitude of short term deterioration was isolated from the long term, and the individual damage mechanisms that were the cause for the majority of the performance deterioration was identified. It was determined that the long term engine performance deterioration characteristics were different for the 3 aircraft types currently powered by the CF6-50 engine, but these differences were due to operational considerations (flight length and takeoff derate) and not to differences associated with the aircraft type. Unrestored losses, that is, performance deterioration which remains after engine refurbishment, represents over 70 percent of the total performance deterioration at engine shop visit. Superficial damage, such as, increased surface roughness, leading edge shape changes on airfoils, and increases in the average clearances between rotating and stationary components is the major contributor to these losses. Seventy one percent of the unrestored losses are cost effective to restore, and if implemented could reduce fuel consumed by CF6-50 engines by 26 million gallons in 1980.

  19. Flying the nest: a challenge for young adults with cystic fibrosis and their parents

    PubMed Central

    Bregnballe, Vibeke; Boisen, Kirsten A; Schiøtz, Peter Oluf; Pressler, Tacjana; Lomborg, Kirsten

    2017-01-01

    Objectives As young patients with cystic fibrosis (CF) grow up, they are expected to take increasing responsibility for the treatment and care of their disease. The aim of this study was to explore the disease-related challenges faced by young adults with CF and their parents, when they leave home. Materials and methods A questionnaire survey of Danish patients with CF aged 18–25 years and their parents was conducted. The questionnaires were based on focus-group interviews with young adults with CF and their parents, and addressed challenges faced in the transition phase between childhood and adulthood, including different areas of disease management in everyday life. Results Among all of the patients invited, 62% (n=58/94) of young adults and 53% (n=99/188) of their parents participated in the study. In total, 40% of the 18- to 25-year-olds were living with their parents, and the parents continued to play an active role in the daily care of their offspring’s disease. Among the young adults who had left home, both the patients and their parents reported many difficulties regarding disease management; the young adults reported difficulties in contacting social services and in affording and preparing sufficient CF-focused meals, and their parents reported difficulties in answering questions concerning social rights and CF in general, and in knowing how to give their offspring the best help, how much to interfere, and how to relinquish control of managing their offspring’s disease. Conclusion Young adults with CF who have left home have difficulties in handling the disease and their parents have difficulties in knowing how to give them the best help. There is an urgent need for holistic CF transitional care, including ensuring that young adults master the essential skills for self-management as they leave their parents. PMID:28243066

  20. Reduced survival in adult cystic fibrosis despite attenuated lung function decline.

    PubMed

    Keating, Claire; Poor, Armeen D; Liu, Xinhua; Chiuzan, Codruta; Backenroth, Daniel; Zhang, Yuan; DiMango, Emily

    2017-01-01

    There is limited data on disease progression and survival in adult diagnosis cystic fibrosis (CF). This study evaluates change of lung function over time and rates of death/lung transplant in adult diagnosis CF. The CF Foundation Patient Registry was reviewed for patients diagnosed 1993-2003. Rate of FEV1 decline was calculated up to 2010 for age groups 6-11, 12-17, and 18 and above. Kaplan Meier method was used for 10 and 15year survival rate calculations for patients diagnosed as adults. Cox Proportional hazards models using predictors affecting disease progression and survival without transplant were run. Between 1993 and 2003, 11,884 patients were diagnosed with CF, of which 2848 were ages 6 and older. Annual rate of change of FEV1% predicted over 5years differed by diagnosis age group: -1.42% per year for ages 6-11, -2.04% for ages 12-17 and -1.13% for ages 18-65 (p<0.0001). Pseudomonas aeruginosa infection was associated with faster rates of lung function decline in all age groups. Survival without transplant for CF patients diagnosed at ≥18years were 76% and 65% by 10 and 15years, respectively. Of adults with FEV1 of >70% predicted at diagnosis, 95% were alive without transplant at 10years, whereas of those with FEV1<40% predicted at diagnosis, 31% were alive without transplant at 10years. Lung function declines at a slower rate in adult diagnosis CF. However, particularly in those with low lung function at diagnosis, rates of death or transplant in adult diagnosis CF after 10 and 15years is not negligible. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  1. Tropospheric photooxidation of CF3CH2CHO and CF3(CH2)2CHO initiated by Cl atoms and OH radicals

    NASA Astrophysics Data System (ADS)

    Antiñolo, M.; Jiménez, E.; Notario, A.; Martínez, E.; Albaladejo, J.

    2009-11-01

    The absolute rate coefficients for the tropospheric reactions of chlorine (Cl) atoms and hydroxyl (OH) radicals with CF3CH2CHO and CF3(CH2)2CHO were measured as a function of temperature (263-371 K) and pressure (50-215 Torr of He) by pulsed UV laser photolysis techniques. Vacuum UV resonance fluorescence was employed to detect and monitor the time evolution of Cl atoms. Laser induced fluorescence was used in this work as a detection of OH radicals as a function of reaction time. No pressure dependence of the bimolecular rate coefficients, kCl and kOH, was found at all temperatures. At room temperature kCl and kOH were (in 10-11 cm3 molecule-1 s-1): kCl(CF3CH2CHO) = (1.55±0.53); kCl(CF3(CH2)2CHO) = (3.39±1.38); kOH(CF3CH2CHO) = (0.259±0.050); kOH(CF3(CH2)2CHO) = (1.28±0.24). A slightly negative temperature dependence of kCl was observed for CF3CH2CHO and CF3(CH2)2CHO, and kOH(CF3CH2CHO). In contrast, kOH(CF3(CH2)2CHO) did not exhibit a temperature dependence in the studied ranged. Arrhenius expressions for these reactions were: kCl(CF3CH2CHO) =(4.4±1.0) × 10-11 exp{-(316±68)/T} cm3 molecule-1 s-1, kCl(CF3(CH2)2CHO) = (2.9±0.7) × 10-10 exp{-625±80)/T} cm3 molecule-1 s-1, kOH(CF3CH2CHO) = (7.8±2.2) × 10-12 exp{-(314±90)/T} cm3 molecule-1 s-1. The atmospheric impact of the homogeneous removal by OH radicals and Cl atoms of these fluorinated aldehydes is discussed in terms of the global atmospheric lifetimes, taking into account different degradation pathways. The calculated lifetimes show that atmospheric oxidation of CF3(CH2)xCHO are globally dominated by OH radicals, however reactions initiated by Cl atoms can act as a source of free radicals at dawn in the troposphere.

  2. Tropospheric photooxidation of CF3CH2CHO and CF3(CH2)2CHO initiated by Cl atoms and OH radicals

    NASA Astrophysics Data System (ADS)

    Antiñolo, M.; Jiménez, E.; Notario, A.; Martínez, E.; Albaladejo, J.

    2010-02-01

    The absolute rate coefficients for the tropospheric reactions of chlorine (Cl) atoms and hydroxyl (OH) radicals with CF3CH2CHO and CF3(CH2)2CHO were measured as a function of temperature (263-371 K) and pressure (50-215 Torr of He) by pulsed UV laser photolysis techniques. Vacuum UV resonance fluorescence was employed to detect and monitor the time evolution of Cl atoms. Laser induced fluorescence was used in this work for the detection of OH radicals as a function of reaction time. No pressure dependence of the bimolecular rate coefficients, kCl and kOH, was found at all temperatures. At room temperature kCl and kOH were (in 10-11 cm3 molecule-1 s-1): kCl(CF3CH2CHO) = (1.55±0.53); kCl(CF3(CH2)2CHO) = (3.39±1.38); kCl(CF3CH2CHO) = (0.259±0.050); kCl(CF3(CH2)2CHO) = (1.28±0.24). A slightly positive temperature dependence of kCl was observed for CF3CH2CHO and CF3(CH2)2CHO, and kOH(CF3CH2CHO). In contrast, kOH(CF3(CH2)2CHO) did not exhibit a temperature dependence over the range investigated. Arrhenius expressions for these reactions were: kCl(CF3CH2CHO) = (4.4±1.0)×10-11 exp{-(316±68)/T} cm3 molecule-1 s-1 kCl(CF3(CH2)2CHO) = (2.9±0.7)×10-10 exp{-(625±80)/T} cm3 molecule-1 s-1 kOH(CF3CH2CHO) = (7.8±2.2)×10-12 exp{-(314±90)/T} cm3 molecule-1 s-1 The atmospheric impact of the homogeneous removal by OH radicals and Cl atoms of these fluorinated aldehydes is discussed in terms of the global atmospheric lifetimes, taking into account different degradation pathways. The calculated lifetimes show that atmospheric oxidation of CF3(CH2)x CHO are globally dominated by OH radicals, however reactions initiated by Cl atoms can act as a source of free radicals at dawn in the troposphere.

  3. CfDS: a team effort

    NASA Astrophysics Data System (ADS)

    Mizon, R.

    2003-02-01

    In 1989, the newly formed BAA Campaign for Dark Skies (CfDS) asked astronomical groups across the UK to nominate members who would actively spread the dark-skies message. Thirty-one 'regional officers' emerged, scattered from Plymouth to near John O'Groats, and from North Wales to the Wash. An unenviable task faced them: a CfDS survey had concluded that more than 90% of British observers, astronomers or not, experienced some degree of skyglow.

  4. CF2 Detection in Radio-Frequency Ar/CHF3 Plasmas by Fourier Transform Infrared Spectroscopy

    NASA Technical Reports Server (NTRS)

    Kim, J. S.; Rao, M. V. V. S.; Cappelli, M. A.; Sharma, S. P.

    1999-01-01

    CFx radicals, in particular CF2, are instrumental in anisotropic etching of SiO2. In order to optimize the CFx radical population in a given process environment, it is imperative that we understand their production mechanism. Towards this goal, we have conducted a series of quantitative measurements of CF2 radicals in low pressure RF plasmas similar to those used in SiO2 etching. In this study, we present preliminary results for Ar/CHF3 plasmas operating at pressures ranging from 10-50 mTorr and powers ranging from 100-500 W in the GEC reference cell, modified for inductive (transformer) coupling. Fourier transform infrared (FTIR) spectroscop) is used to observe the absorption features of the CF2 radical in the 1114 cm-1 and 1096 cm-1 spectral regions. The FTIR spectrometer is equipped with a high-sensitivity mercury cadmium telluride (MCT) detector and has afixed resolution of 0.125 cm- 1. The CF2 concentrations are measured for a range of operating pressures and discharge power levels, and are compared to measurements of the relative CF2 concentrations made by mass spectrometry using the method of appearance potential for radical selectivity.

  5. Electron attachment to CF3 and CF3Br at temperatures up to 890 K: experimental test of the kinetic modeling approach.

    PubMed

    Shuman, Nicholas S; Miller, Thomas M; Viggiano, Albert A; Troe, Jürgen

    2013-05-28

    Thermal rate constants and product branching fractions for electron attachment to CF3Br and the CF3 radical have been measured over the temperature range 300-890 K, the upper limit being restricted by thermal decomposition of CF3Br. Both measurements were made in Flowing Afterglow Langmuir Probe apparatuses; the CF3Br measurement was made using standard techniques, and the CF3 measurement using the Variable Electron and Neutral Density Attachment Mass Spectrometry technique. Attachment to CF3Br proceeds exclusively by the dissociative channel yielding Br(-), with a rate constant increasing from 1.1 × 10(-8) cm(3) s(-1) at 300 K to 5.3 × 10(-8) cm(3) s(-1) at 890 K, somewhat lower than previous data at temperatures up to 777 K. CF3 attachment proceeds through competition between associative attachment yielding CF3 (-) and dissociative attachment yielding F(-). Prior data up to 600 K showed the rate constant monotonically increasing, with the partial rate constant of the dissociative channel following Arrhenius behavior; however, extrapolation of the data using a recently proposed kinetic modeling approach predicted the rate constant to turn over at higher temperatures, despite being only ~5% of the collision rate. The current data agree well with the previous kinetic modeling extrapolation, providing a demonstration of the predictive capabilities of the approach.

  6. Safety design considerations for lithium batteries in CF applications

    NASA Astrophysics Data System (ADS)

    Moroz, W. J.

    1981-02-01

    Lithium-sulphur dioxide (Li-SO2) primary cells are being introduced as power supplies into Canadian Forces applications where advantage can be taken of their high energy density characteristics and low temperature capabilities. For safety reasons the high energy capabilities of these cells must be protected against the possibility of accidental abuse. DREO has investigated and identified a number of operational problem areas associated with Li-SO2 systems. Safety design considerations are proposed for three CF applications; the PRC 515 Radio Set/Radar Transponder SST-181X applications and the AN/PRQ-501 Personal Locater Beacon.

  7. Work disability in adults with cystic fibrosis.

    PubMed

    Gillen, M; Lallas, D; Brown, C; Yelin, E; Blanc, P

    1995-07-01

    Greater numbers of persons with cystic fibrosis (CF) reach adulthood and, therefore, actively participate in the labor force. In this study, we estimated labor force participation rates and determined risk factors for work disability among persons with CF. We recruited 49 (73%) of 67 adults followed at one of two hospital-based CF centers. We ascertained employment history and CF-attributed work disability by structured questionnaire. Independently, we reviewed medical records for demographics and illness severity indicators. We analyzed potential risk factors for work disability by logistic regression analysis. All of those studied reported past or present labor force participation, consistent with high work motivation. Complete cessation of work attributed to CF was reported by 17 (35%; 95% CI, 21 to 49%). Although 23 (47%; 95% CI, 32 to 60%) of those surveyed stated that CF had affected career choice, only nine respondents had ever received career counselling and 16 had ever discussed job choice with their physicians. After adjusting for standard measures of disease severity by multiple logistic regression, age, adult diagnosis of CF, female gender, and single marital status, analyzed as a group, provided significant additional explanatory power to a predictive model of disability risk (model chi square [4 d.f.] = 11.5, p < 0.05). Health care professionals who design interventions targeted at work disability among persons with CF should address demographic factors as well as illness severity and should assess the vocational needs of persons with CF and the potential benefit of career counselling.

  8. Effective ionization coefficients, limiting electric fields, and electron energy distributions in CF{sub 3}I + CF{sub 4} + Ar ternary gas mixtures

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

    Tezcan, S. S.; Dincer, M. S.; Bektas, S.

    2016-07-15

    This paper reports on the effective ionization coefficients, limiting electric fields, electron energy distribution functions, and mean energies in ternary mixtures of (Trifluoroiodomethane) CF{sub 3}I + CF{sub 4} + Ar in the E/N range of 100–700 Td employing a two-term solution of the Boltzmann equation. In the ternary mixture, CF{sub 3}I component is increased while the CF{sub 4} component is reduced accordingly and the 40% Ar component is kept constant. It is seen that the electronegativity of the mixture increases with increased CF{sub 3}I content and effective ionization coefficients decrease while the limiting electric field values increase. Synergism in themore » mixture is also evaluated in percentage using the limiting electric field values obtained. Furthermore, it is possible to control the mean electron energy in the ternary mixture by changing the content of CF{sub 3}I component.« less

  9. Progress in cystic fibrosis and the CF Therapeutics Development Network

    PubMed Central

    Rowe, Steven M; Borowitz, Drucy S; Burns, Jane L; Clancy, John P; Donaldson, Scott H; Retsch-Bogart, George; Sagel, Scott D; Ramsey, Bonnie W

    2013-01-01

    Cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians, affects approximately 70 000 individuals worldwide. In 1998, the Cystic Fibrosis Foundation (CFF) launched the CF Therapeutics Development Network (CF-TDN) as a central element of its Therapeutics Development Programme. Designed to accelerate the clinical evaluation of new therapies needed to fulfil the CFF mission to control and cure CF, the CF-TDN has conducted 75 clinical trials since its inception, and has contributed to studies as varied as initial safety and proof of concept trials to pivotal programmes required for regulatory approval. This review highlights recent and significant research efforts of the CF-TDN, including a summary of contributions to studies involving CF transmembrane conductance regulator (CFTR) modulators, airway surface liquid hydrators and mucus modifiers, anti-infectives, anti-inflammatories, and nutritional therapies. Efforts to advance CF biomarkers, necessary to accelerate the therapeutic goals of the network, are also summarised. PMID:22960984

  10. Progress in cystic fibrosis and the CF Therapeutics Development Network.

    PubMed

    Rowe, Steven M; Borowitz, Drucy S; Burns, Jane L; Clancy, John P; Donaldson, Scott H; Retsch-Bogart, George; Sagel, Scott D; Ramsey, Bonnie W

    2012-10-01

    Cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians, affects approximately 70 000 individuals worldwide. In 1998, the Cystic Fibrosis Foundation (CFF) launched the CF Therapeutics Development Network (CF-TDN) as a central element of its Therapeutics Development Programme. Designed to accelerate the clinical evaluation of new therapies needed to fulfil the CFF mission to control and cure CF, the CF-TDN has conducted 75 clinical trials since its inception, and has contributed to studies as varied as initial safety and proof of concept trials to pivotal programmes required for regulatory approval. This review highlights recent and significant research efforts of the CF-TDN, including a summary of contributions to studies involving CF transmembrane conductance regulator (CFTR) modulators, airway surface liquid hydrators and mucus modifiers, anti-infectives, anti-inflammatories, and nutritional therapies. Efforts to advance CF biomarkers, necessary to accelerate the therapeutic goals of the network, are also summarised.

  11. Cystic fibrosis: addressing the transition from pediatric to adult-oriented health care.

    PubMed

    Kreindler, James L; Miller, Victoria A

    2013-12-11

    Survival for patients with cystic fibrosis (CF) increased to nearly 40 years in 2012 from the early childhood years in the 1940s. Therefore, patients are living long enough to require transition from pediatric CF centers to adult CF centers. The goal of transition is for the young adult to be engaged in the adult health care system in ways that optimize health, maximize potential, and increase quality of life. A successful transition promotes autonomy and responsibility with respect to one's own health. Currently, there is an information gap in the literature with respect to psychological models that can help guide informed transition processes. In this review, we establish the framework in which transition exists in CF; we review some of the published literature from the last 20 years of experience with transition in CF centers around the world; and we discuss psychological models of pediatric illness that can help to explain the current state of transition to adult-oriented care from pediatric-oriented care and help to formulate new models of ascertaining readiness for transition. Finally, we look at our current knowledge gaps and opportunities for future research endeavors.

  12. Uptake of dissolved inorganic and organic nitrogen by the benthic toxic dinoflagellate Ostreopsis cf. ovata.

    PubMed

    Jauzein, Cécile; Couet, Douglas; Blasco, Thierry; Lemée, Rodolphe

    2017-05-01

    Environmental factors that shape dynamics of benthic toxic blooms are largely unknown. In particular, for the toxic dinoflagellate Ostreopsis cf. ovata, the importance of the availability of nutrients and the contribution of the inorganic and organic pools to growth need to be quantified in marine coastal environments. The present study aimed at characterizing N-uptake of dissolved inorganic and organic sources by O. cf. ovata cells, using the 15 N-labelling technique. Experiments were conducted taking into account potential interactions between nutrient uptake systems as well as variations with the diel cycle. Uptake abilities of O. cf. ovata were parameterized for ammonium (NH 4 + ), nitrate (NO 3 - ) and N-urea, from the estimation of kinetic and inhibition parameters. In the range of 0 to 10μmolNL -1 , kinetic curves showed a clear preference pattern following the ranking NH 4 + >NO 3 - >N-urea, where the preferential uptake of NH 4 + relative to NO 3 - was accentuated by an inhibitory effect of NH 4 + concentration on NO 3 - uptake capabilities. Conversely, under high nutrient concentrations, the preference for NH 4 + relative to NO 3 - was largely reduced, probably because of the existence of a low-affinity high capacity inducible NO 3 - uptake system. Ability to take up nutrients in darkness could not be defined as a competitive advantage for O. cf. ovata. Species competitiveness can also be defined from nutrient uptake kinetic parameters. A strong affinity for NH 4 + was observed for O. cf. ovata cells that may partly explain the success of this toxic species during the summer season in the Bay of Villefranche-sur-mer (France). Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Continuous alternating inhaled antibiotic therapy in CF: A single center retrospective analysis.

    PubMed

    Van de Kerkhove, C; Goeminne, P C; Kicinski, M; Nawrot, T S; Lorent, N; Van Bleyenbergh, P; De Boeck, K; Dupont, L J

    2016-11-01

    The efficacy of inhaled antibiotics to treat chronic Pseudomonas aeruginosa pulmonary infection in patients with cystic fibrosis (CF) has been well established. Few data are available on the value of continuous alternating inhaled antibiotic therapy (CAIT), a strategy increasingly used in the management of CF. To investigate the effect of CAIT on clinical outcome in adult CF patients treated at the University Hospital Leuven. Patients with a documented CF diagnosis who received inhaled antibiotics between March 2010 and January 2015 were retrospectively evaluated. In patients receiving CAIT patient characteristics, recorded spirometry data and number of IV antibiotic days were collected retrospectively at fixed time intervals, from 6months before to one year after the start of the 2nd inhaled antibiotic. For patients on inhaled antibiotic monotherapy (IAMT), the same data were obtained at similar intervals during the study period. A total of 49 of 89 patients using chronic inhaled antibiotic therapy received CAIT. Patients receiving CAIT had a lower baseline FEV 1 and were more likely to be homozygous for F508del compared to patients receiving IAMT. FEV 1 deteriorated on average by a factor of 0.904 per year (95% CI: 0.851-0.960) prior to the start of CAIT. The initiation of CAIT was associated with an average improvement in FEV 1 by a factor of 1.148 per year (95% CI: 1.068-1.236, p=0.0002). The analysis of specific types of antibiotics revealed evidence of positive effects of adding COLI to TOBI and COLI to AZLI. We found no effect of the initiation of CAIT on the number of IV antibiotic days (p=0.80). CF patients with more advanced lung disease are more likely to receive CAIT. In this patient group, CAIT was associated with a significant improvement in FEV 1 . Further data are warranted to identify the value of CAIT. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  14. Ion Energy and Ion Flux Distributions of CF4/Ar/O2 Inductively Coupled Plasmas in a GEC Cell

    NASA Technical Reports Server (NTRS)

    Rao, M. V. V. S.; Cruden, Brett; Sharma, Surendra; Meyyappan, Meyya

    2001-01-01

    Knowledge of ion kinetics in plasma processing gas mixtures, such as CF4:Ar:O2, is important for understanding plasma assisted etching and deposition of materials. Ion energies and ion fluxes were measured in this mixture for 80:10:10, 60:20:20, and 40:30:30 mixture ratios in the pressure range of 10-50 mTorr, and at 200 and 300 W of RF power. Ions from plasma, sampled through a 10 micron orifice in the center of the lower plane electrode, were energy and mass analyzed by a combination of electrostatic energy and quadrupole mass filters. CFx(+) (x = 1 - 3), F2(+), F(+), C(+) from CF4, Ar(+) from Ar, and O2(+) and O(+) from O2, and by-product ions SiFx(+)(x = 1 - 3) from etching of quartz coupling window, COFx(+)(x = 1 - 3), CO(+), CO2(+), and OF(+) were detected. In all conditions ion flux decreases with increase of pressure but increase with increase of RF power. Ar(+) signal decreases with increase of pressure while CF3(+), which is the dominant ion at all conditions, increases with increase in pressure. The loss mechanism for Ar(+) and increase of CF3(+) is due to large cross section for Ar(+) + CF4 yields Ar + CF3(+) + F. Ion energies, which range from 15-25 eV depending on plasma operating conditions, are nearly Gaussian. By-product ion signals are higher at lower pressures indicating stronger plasma interaction with quartz window.

  15. Fluorous Peptide Nucleic Acids: PNA Analogues with Fluorine in Backbone (γ-CF2-apg-PNA) Enhance Cellular Uptake.

    PubMed

    Ellipilli, Satheesh; Ganesh, Krishna N

    2015-09-18

    Fluorous PNA analogues possessing fluorine as inherent part of aminopropylglycine (apg) backbone (γ-CF2-apg PNA) have been synthesized and evaluated for biophysical and cell penetrating properties. These form duplexes of higher thermal stability with cRNA than cDNA, although destabilized compared to duplexes of standard aeg-PNA. Cellular uptake of the fluorinated γ-CF2-apg PNAs in NIH 3T3 and HeLa cells was 2-3-fold higher compared to that of nonfluorinated apg PNA, with NIH 3T3 cells showing better permeability compared to HeLa cells. The backbone fluorinated PNAs, which are first in this class, when combined with other chemical modifications may have potential for future PNA-based antisense agents.

  16. Apparatus and method for generating continuous wave 16. mu. m laser radiation using gaseous CF/sub 4/

    DOEpatents

    Telle, J.M.

    1984-05-01

    Apparatus and method for generating continuous wave 16 ..mu..m laser radiation using gaseous CF/sub 4/. Laser radiation at 16 ..mu..m has been observed in a cooled static cell containing low pressure CF/sub 4/ optically pumped by an approximately 3 W output power c-w CO/sub 2/ laser. The laser cavity employed was a multiple-pass off-axis-path two spherical mirror ring resonator. Unidirectional CF/sub 4/ laser output power at 615 cm/sup -1/ exceeded 2 mW. Computer calculations indicate that for modest pump powers of about 40 W, approximately 1 W of emitted laser radiation at 16 ..mu..m might be obtained.

  17. Apparatus and method for generating continuous wave 16 .mu.m laser radiation using gaseous CF.sub.4

    DOEpatents

    Telle, John M.

    1986-01-01

    Apparatus and method for generating continuous wave 16 .mu.m laser radiation using gaseous CF.sub.4. Laser radiation at 16 .mu.m has been observed in a cooled static cell containing low pressure CF.sub.4 optically pumped by an approximately 3 W output power cw CO.sub.2 laser. The laser cavity employed was a multiple-pass off-axis-path two spherical mirror ring resonator. Unidirectional CF.sub.4 laser output power at 615 cm.sup.-1 exceeded 2 mW. Computer calculations indicate that for modest pump powers of about 40 W, approximately 1 W of emitted laser radiation at 16 .mu.m might be obtained.

  18. Comparison of intestine and bone marrow radiosensitivity of the BALB/c and the C57BL/6 mouse strains and their B6CF1 offspring

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

    Hanson, W.R.; Fry, R.J.; Sallese, A.R.

    1987-06-01

    The radiosensitivity as measured by LD50/6 or LD50/30 of the F1 hybrid B6CF1 (C57BL/6 X BALB/c) is similar to that of C57BL/6 mice but markedly different from BALB/c. The LD50/6 for BALB/c mice was about 8.8 Gy compared to 16.4 Gy for the B6CF1. The difference in LD50/6 between the parent strains or between BALB/c and the F1 hybrid could not be explained by any differences in crypt cell number, cell cycle time, or transit time. Likewise, the observed differences in the LD50/6 do not appear to result from marked differences in the radiosensitivity of marrow stem cells (CFU-S) sincemore » the D0's for the three genotypes of mice were similar. Also, there were no apparent differences in the red blood cell contents of several enzymes associated with antioxidant defenses. The microcolony assay was used to determine the D0 for the crypt clonogenic cells and the D0 values for 60Co gamma rays were about 0.8 Gy for BALB/c mice and 1.4 Gy for B6CF1 mice. However, the D0 values for JANUS fission neutrons were similar; 0.6 Gy for the BALB/c mice and 0.5 for the B6CF1 mice. A comparison of clonogenic cell kinetics, using prolonged colcemid block to distinguish between slowly and rapidly cycling cells suggest that, normally, the stem cells are slowly cycling in both the BALB/c and the B6CF1 hybrid. However, the stem cells of the B6CF1 appear to go into rapid cell cycle more rapidly than those of the BALB/c following irradiation or prolonged colcemid treatment. The more rapid recovery in intestinal epihelial cell production in the B6CF1 hybrid after irradiation may provide an increased mucosal barrier and may, in part, explain the difference in the response to radiation compared to that in the BALB/c.« less

  19. cfDNA as an Earlier Predictor of Exercise-Induced Performance Decrement Related to Muscle Damage.

    PubMed

    Andreatta, Michely V; Curty, Victor M; Coutinho, João Victor S; Santos, Miguel Ângelo A; Vassallo, Paula F; de Sousa, Nuno F; Barauna, Valério G

    2017-11-28

    The aims of this study were: a) to evaluate whether cell-free DNA (cfDNA) levels increase immediately after an acute light and heavy resistance exercise (RE) bout, and b) to whether cfDNA levels are associated with functional muscle capacity until 48hrs after exercise session. Twenty healthy volunteers performed 3 sets of the leg press resistance exercise with 80% of 1RM (RE80) or 40% of 1RM (RE40) with similar exercise volume. Blood lactate was measured after completion of the 3 sets. Creatine kinase (CK), cfDNA and jump performance were evaluated before (pre) exercise, immediately post-exercise (Post-0) and every 24hrs until 48hrs. Lactate concentration increased similarly in both groups (RE40, 4.0±1.3mmol/L; RE80, 4.8±1.3mmol/L). No changes were observed in squat jump and countermovement jump performance after RE40, however both jumps remained reduced until 48h in RE80 group. CK concentration increased post-24h only in the RE80 group (Pre: 128.8±73.7U/L to Post-24h: 313.8±116.4U/L). cfDNA concentration increased post-0h only in the RE80 group (Pre, 249.8±82.3ng/mL; Post-0h, 406.3±67.2ng/mL). There was a negative correlation between post-0h cfDNA concentration and post-24h squat jump (r=-0.521; p=0.01) and post-0h cfDNA concentration and post-24h countermovement jump (r=-0.539; p=0.01). cfDNA increases in responsive to RE intensity even when not performed until exhaustion. cfDNA measured immediately after RE is a promising biomarker for muscle performance decrement until 48hrs of a RE bout.

  20. The infrared spectral analysis of CF/sub 2Cl/sub 2

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The CF2Cl2 absorption bands at 1/923 cm and 1/1161 cm are examined as to their detectability in long-path solar spectroscopy. Measurements are reported for a long-path White Cell. A cryo-condensation unit was also constructed to test its ability to improve detection of trace gases in the ambient atmosphere.

  1. Adult Stem Cells and Diseases of Aging

    PubMed Central

    Boyette, Lisa B.; Tuan, Rocky S.

    2014-01-01

    Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

  2. Experiences of adults with cystic fibrosis in adhering to medication regimens: a qualitative systematic review.

    PubMed

    Macdonald, Marilyn; Martin-Misener, Ruth; Helwig, Melissa; Smith, Lisa Janette; Godfrey, Christina M; Curran, Janet; Murphy, Andrea

    2016-05-01

    Adherence of adults with cystic fibrosis (CF) to medication regimens has been documented as problematic. Research related to adherence from the perspectives of adults with CF has been recommended for a further understanding of adherence. This review synthesized the qualitative evidence on adherence of adults with CF to medication regimens and should be of interest to healthcare providers. The question addressed in this review is, what are the experiences and perceptions of adults with CF and their adherence to a medication regimen? Adults with CF who are maintaining a medication regimen. The phenomenon of interest of this review is the experiences and perceptions of CF-affected adults who are taking prescribed medications to treat their CF and related conditions. This review included qualitative studies with the following designs: naturalistic inquiry, grounded theory, phenomenology and interpretive description. The gray literature was searched; however, no items were retained for the review. The search strategy used a three-step approach and was aimed at locating both published and unpublished studies. Key databases included, but were not limited to, CINAHL, PubMed and PsycINFO. The searches were not limited by date or language because we wanted to capture all existing qualitative studies related to the experiences and perceptions of adults following medication regimens. During the title and abstract screening, only English and French articles were included. Qualitative studies triaged for appraisal were assessed by two Joanna Briggs Institute (JBI)-certified reviewers for methodological quality before inclusion. The reviewers used the JBI critical appraisal instruments, specifically the JBI Qualitative Assessment and Review Instrument (JBI-QARI). Data were independently extracted from the studies included in the review by two reviewers using the standardized data extraction tool from JBI-QARI. Data were synthesized using the JBI process of meta

  3. Cell phone intervention to improve adherence: cystic fibrosis care team, patient, and parent perspectives.

    PubMed

    Marciel, Kristen K; Saiman, Lisa; Quittell, Lynne M; Dawkins, Kevin; Quittner, Alexandra L

    2010-02-01

    Treatment regimens for patients with cystic fibrosis (CF) are time-consuming and complex, resulting in consistently low adherence rates. To date, few studies have evaluated innovative technologies to improve adherence in this population. Current infection control guidelines for patients with CF seek to minimize patient-to-patient transmission of potential pathogens. Thus, interventions must avoid face-to-face contact and be delivered individually, limiting opportunities for peer support. This study aimed to develop and assess a web-enabled cell phone, CFFONE, designed to provide CF information and social support to improve adherence in adolescents with CF. The acceptability, feasibility, and utility of CFFONE were evaluated with health care professionals (n = 17) adolescents with CF aged 11-18 years old (n = 12), adults with CF aged 21-36 years old (n = 6), parents of adolescents with CF (n = 12), and technology experts (n = 8). Adolescents also tested a prototype of CFFONE (n = 9). Qualitative and quantitative data were collected. Focus group data with health care professionals indicated a need for this intervention, and indicated that CFFONE would be likely to improve knowledge and social support, and somewhat likely to improve adherence. Adolescent, adults, and parents all rated CFFONE as likely to improve adherence. Technology experts rated the prototype design and format as appropriate. The current study provided some support from key stakeholders for this intervention to improve adherence in adolescents with CF. Next steps include a multi-center trial of the efficacy and safety of CFFONE. (c) 2010 Wiley-Liss, Inc.

  4. Differential Effects of Focused and Unfocused Written Correction on the Accurate Use of Grammatical Forms by Adult ESL Learners

    ERIC Educational Resources Information Center

    Sheen, Younghee; Wright, David; Moldawa, Anna

    2009-01-01

    Building on Sheen's (2007) study of the effects of written corrective feedback (CF) on the acquisition of English articles, this article investigated whether direct focused CF, direct unfocused CF and writing practice alone produced differential effects on the accurate use of grammatical forms by adult ESL learners. Using six intact adult ESL…

  5. Adult neural stem cells: The promise of the future

    PubMed Central

    Taupin, Philippe

    2007-01-01

    Stem cells are self-renewing undifferentiated cells that give rise to multiple types of specialized cells of the body. In the adult, stem cells are multipotents and contribute to homeostasis of the tissues and regeneration after injury. Until recently, it was believed that the adult brain was devoid of stem cells, hence unable to make new neurons and regenerate. With the recent evidences that neurogenesis occurs in the adult brain and neural stem cells (NSCs) reside in the adult central nervous system (CNS), the adult brain has the potential to regenerate and may be amenable to repair. The function(s) of NSCs in the adult CNS remains the source of intense research and debates. The promise of the future of adult NSCs is to redefine the functioning and physiopathology of the CNS, as well as to treat a broad range of CNS diseases and injuries. PMID:19300610

  6. Elements of the niche for adult stem cell expansion

    PubMed Central

    Redondo, Patricia A; Pavlou, Marina; Loizidou, Marilena; Cheema, Umber

    2017-01-01

    Adult stem cells are crucial for tissue homeostasis. These cells reside within exclusive locations in tissues, termed niches, which protect adult stem cell fidelity and regulate their many functions through biophysical-, biochemical- and cellular-mediated mechanisms. There is a growing understanding of how these mechanisms and their components contribute towards maintaining stem cell quiescence, self-renewal, expansion and differentiation patterns. In vitro expansion of adult stem cells is a powerful tool for understanding stem cell biology, and for tissue engineering and regenerative medicine applications. However, it is technically challenging, since adult stem cell removal from their native microenvironment has negative repercussions on their sustainability. In this review, we overview specific elements of the biomimetic niche and how recreating such elements can help in vitro propagation of adult stem cells. PMID:28890779

  7. Elements of the niche for adult stem cell expansion.

    PubMed

    Redondo, Patricia A; Pavlou, Marina; Loizidou, Marilena; Cheema, Umber

    2017-01-01

    Adult stem cells are crucial for tissue homeostasis. These cells reside within exclusive locations in tissues, termed niches, which protect adult stem cell fidelity and regulate their many functions through biophysical-, biochemical- and cellular-mediated mechanisms. There is a growing understanding of how these mechanisms and their components contribute towards maintaining stem cell quiescence, self-renewal, expansion and differentiation patterns. In vitro expansion of adult stem cells is a powerful tool for understanding stem cell biology, and for tissue engineering and regenerative medicine applications. However, it is technically challenging, since adult stem cell removal from their native microenvironment has negative repercussions on their sustainability. In this review, we overview specific elements of the biomimetic niche and how recreating such elements can help in vitro propagation of adult stem cells.

  8. Effects of nitrogen supply on Pseudo-nitzschia calliantha and Pseudo-nitzschia cf. seriata: field and laboratory experiments.

    PubMed

    Melliti Ben Garali, Sondes; Sahraoui, Inès; de la Iglesia, Pablo; Chalghaf, Mohamed; Diogène, Jorge; Ksouri, Jamel; Sakka Hlaili, Asma

    2016-08-01

    The effects of inorganic and organic nitrogen supply on the growth and domoic acid (DA) production of Pseudo-nitzschia cf. seriata and Pseudo-nitzschia calliantha from Bizerte Lagoon (SW Mediterranean Sea) were studied during field and laboratory experiments. Nitrogen enrichments (40 µM NO3 (-); 10 µM NH4 (+); 20 µM CH4N2O) and a control, with no added N, were carried out in separate carboys with seawater collected from Bizerte Lagoon. In the field experiments, all N-enrichments resulted in significant increases in chlorophyll a concentration, and maintained exponential growth until the end of the experiment. The initial diatom community was dominated by a bloom of P. cf. seriata (9.3 × 10(5) cells l(-1)). After 6 days of incubation, the abundance of P. cf. seriata was greatest in the urea addition (1.52 × 10(6) cells l(-1)), compared to the ammonium treatment (0.47 × 10(6) cells l(-1)), nitrate treatment (0.70 × 10(6) cells l(-1)) and control (0.36 × 10(6) cells l(-1)). The specific growth rates, calculated from increases in chlorophyll a and cell abundance, were statistically different across all treatments, with the highest in the urea and nitrate additions. Similar results were obtained from the laboratory experiments. These were carried out with P. calliantha isolated from Bizerte Lagoon and grown in f/2 medium enriched with 40 µM nitrate, 10 µM ammonium and 20 µM urea. The exponential growth rate was significantly faster for the cells cultured with urea (1.50 d(-1)) compared to the nitrate (0.90 d(-1)) and ammonium (0.80 d(-1)) treatments and the control (0.40 d(-1)). Analysis of DA, performed at the beginning and the end of the both experiments in all treatments, revealed very low concentrations (below the limit of quantification, 0.02- 1.310(-7) pg cell(-1), respectively).The field and laboratory experiments demonstrate that P.cf. seriata and P. calliantha are able to grow efficiently on the three forms of N, but with a

  9. Sleep Disorders in Adult Sickle Cell Patients

    PubMed Central

    Sharma, Sunil; Efird, Jimmy T.; Knupp, Charles; Kadali, Renuka; Liles, Darla; Shiue, Kristin; Boettger, Peter; Quan, Stuart F.

    2015-01-01

    Study Objectives: While sleep apnea has been studied in children with sickle cell disease (SCD), little is known about sleep disorders in adult sickle cell patients. The objective of this study was to evaluate sleep disordered breathing and its polysomnographic characteristics in adult patients with sickle cell disease. Methods: The analysis cohort included 32 consecutive adult SCD patients who underwent a comprehensive sleep evaluation and overnight polysomnography in an accredited sleep center after reporting symptoms suggesting disordered sleep or an Epworth Sleepiness Scale score ≥ 10. Epworth score, sleep parameters, comorbid conditions, and narcotic use were reviewed and compared in patients with and without sleep disordered breathing. SCD complication rates in the two groups also were compared. Results: In adult SCD patients who underwent overnight polysomnography, we report a high prevalence (44%) of sleep disordered breathing. Disease severity was mild to moderate (mean apnea-hypopnea index = 17/h (95% CI: 10–24/h). Concomitant sleep disorders, including insomnia complaints (57%) and delayed sleep-phase syndrome (57%), also were common in this population. In this limited cohort, we did not find increased SCD complications associated with sleep disordered breathing in adult patients with sickle cell disease. Conclusions: A high burden of sleep disordered breathing and other sleep-related complaints were identified in the adult sickle cell population. Our results provide important information on this unique population. Citation: Sharma S, Efird JT, Knupp C, Kadali R, Liles D, Shiue K, Boettger P, Quan SF. Sleep disorders in adult sickle cell patients. J Clin Sleep Med 2015;11(3):219–223. PMID:25515282

  10. The etiologies of non-CF bronchiectasis in childhood: a systematic review of 989 subjects.

    PubMed

    Brower, Kelly S; Del Vecchio, Michael T; Aronoff, Stephen C

    2014-12-10

    While cystic fibrosis (CF) is the most common cause of bronchiectasis in childhood, non-CF bronchiectasis is associated with a wide variety of disorders. The objective of this study was to determine the relative prevalence and specific etiologies on non-CF bronchiectasis in childhood. EMBASE, Medline, OVID Cochrane Reviews, Directory of Open Access Journals, Open Science Directory, EPSCO information services, and OAlster were searched electronically and the bibliographies of selected studies were searched manually. The search was conducted independently by 2 authors. (1) any clinical trial, observational study or cross-sectional case series of 10 or more patients with a description of the conditions associated with bronchiectasis; (2) subjects aged 21 years or younger; (3) cystic fibrosis was excluded and; (4) the diagnosis was confirmed by computed tomography of the chest. Patient number, age range, inclusion criteria, diagnostic criteria, patient source, and categorical and specific etiology. From 491 studies identified, 12 studies encompassing 989 children with non-CF bronchiectasis were selected. Sixty-three percent of the subjects had an underlying disorder. Infectious (17%), primary immunodeficiency (16%), aspiration (10%), ciliary dyskinesia (9%), congenital malformation (3%), and secondary immunodeficiency (3%) were the most common disease categories; 999 etiologies were identified. Severe pneumonia of bacterial or viral etiology and B cell defects were the most common disorders identified. The majority of children with non-CF bronchiectasis have an underlying disorder. A focused history and laboratory investigated is recommended.

  11. In search of adult renal stem cells.

    PubMed

    Anglani, F; Forino, M; Del Prete, D; Tosetto, E; Torregrossa, R; D'Angelo, A

    2004-01-01

    The therapeutic potential of adult stem cells in the treatment of chronic degenerative diseases has becoming increasingly evident over the last few years. Significant attention is currently being paid to the development of novel treatments for acute and chronic kidney diseases too. To date, promising sources of stem cells for renal therapies include adult bone marrow stem cells and the kidney precursors present in the early embryo. Both cells have clearly demonstrated their ability to differentiate into the kidney's specialized structures. Adult renal stem cells have yet to be identified, but the papilla is where the stem cell niche is probably located. Now we need to isolate and characterize the fraction of papillary cells that constitute the putative renal stem cells. Our growing understanding of the cellular and molecular mechanisms behind kidney regeneration and repair processes - together with a knowledge of the embryonic origin of renal cells - should induce us, however, to bear in mind that in the kidney, as in other mesenchymal tissues, the need for a real stem cell compartment might be less important than the phenotypic flexibility of tubular cells. Thus, by displaying their plasticity during kidney maintenance and repair, terminally differentiated cells may well function as multipotent stem cells despite being at a later stage of maturation than adult stem cells. One of the major tasks of Regenerative Medicine will be to disclose the molecular mechanisms underlying renal tubular plasticity and to exploit its biological and therapeutic potential.

  12. Progenitor cell domains in the developing and adult pancreas

    PubMed Central

    Kopp, Janel L; Dubois, Claire L; Hao, Ergeng; Thorel, Fabrizio; Herrera, Pedro L

    2011-01-01

    Unlike organs with defined stem cell compartments, such as the intestine, the pancreas has limited capacity to regenerate. The question of whether the adult pancreas harbors facultative stem/progenitor cells has been a prime subject of debate. Cumulative evidence from recent genetic lineage tracing studies, in which specific cell populations were marked and traced in adult mice, suggests that endocrine and acinar cells are no longer generated from progenitors in the adult pancreas. These studies further indicate that adult pancreatic ductal cells are not a source for endocrine cells following pancreatic injury, as previously suggested. Our own studies have shown that adult ductal cells reinitiate expression of some endocrine progenitor markers, including Ngn3, after injury by partial duct ligation (PDL), but that these cells do not undergo endocrine cell differentiation. Here, we present additional evidence that endocrine cells do not arise from ducts following β-cell ablation by streptozotocin or by a diphtheria toxin-expressing transgene or when β-cell ablation is combined with PDL. In this review, we discuss findings from recent lineage tracing studies of embryonic and adult pancreatic ductal cells. Based upon the combined evidence from these studies, we propose that multipotency is associated with a specific transcriptional signature. PMID:21558806

  13. Electron and positron scattering from CF 3I molecules below 600 eV: a comparison with CF 3H

    NASA Astrophysics Data System (ADS)

    Kawada, Michihito K.; Sueoka, Osamu; Kimura, Mineo

    2000-11-01

    The total cross-sections (TCSs) for electron and positron scattering from CF 3I molecules have been studied experimentally. A theoretical analysis based on the continuum multiple-scattering (CMS) method has been performed to understand the origin of resonances and the elastic cross-sections. The present TCS for electron scattering is found to be larger by about 20% than that of T. Underwood-Lemons, D.C. Winkler, J.A. Tossel, J.H. Moore [J. Chem. Phys. 100 (1994) 9117] although the general shape agrees well in the entire energy studied. The difference in the cross-sections for CF 3I and CF 3H is explained by the sizes and the dipole moments of these molecules.

  14. Commentary: "re-programming or selecting adult stem cells?".

    PubMed

    Trosko, James E

    2008-01-01

    The recent observations that embryonic stemness-associated genes could assist in the "de-differentiation" of adult skin fibroblast cells to "embryonic-like stem cells", using the "somatic cell nuclear transfer" techniques, have been interpreted as indicating a "re-programming" of genes. These reports have demonstrated a "proof of principle" approach to by-pass many, but not all, of the ethical, scientific and medical limitations of the "therapeutic cloning" of embryonic stem cells from embryos. However, while the interpretation that real "re-programming" of all those somatic fibroblastic differentiation genes might be correct, there does exists an alternative hypothesis of these exciting results. Based on the fact that multipotent adult stem cells exist in most, if not all, adult organs, the possibility exists that all these recent "re-programming" results, using the somatic nuclear transfer techniques, actually were the results of transferred rare nuclear material from the adult stem cells residing in the skin of the mouse, monkey and human samples. An examination of the rationale for this challenging hypothesis has been drawn from the hypothesis of the "stem cell theory of cancer", as well as from the field of human adult stem cells research.

  15. Cover/Frequency (CF)

    Treesearch

    John F. Caratti

    2006-01-01

    The FIREMON Cover/Frequency (CF) method is used to assess changes in plant species cover and frequency for a macroplot. This method uses multiple quadrats to sample within-plot variation and quantify statistically valid changes in plant species cover, height, and frequency over time. Because it is difficult to estimate cover in quadrats for larger plants, this method...

  16. Calculation and characteristic analysis on synergistic effect of CF3I gas mixtures

    NASA Astrophysics Data System (ADS)

    Su, ZHAO; Yunkun, DENG; Yuhao, GAO; Dengming, XIAO

    2018-06-01

    CF3I is a potential SF6 alternative gas. In order to study the insulation properties and synergistic effects of CF3I/N2 and CF3I/CO2 gas mixtures, two-term approximate Boltzmann equations were used to obtain the ionization coefficient α, attachment coefficient η and the critical equivalent electrical field strength (E/N)cr. The results show that the (E/N)cr of CF3I gas at 300 K is 1.2 times that of SF6 gas, and CF3I/N2 and CF3I/CO2 gas mixtures both have synergistic effect occurred. The synergistic effect coefficient of CF3I/CO2 gas mixture was higher than that of CF3I/N2 gas mixture. But the (E/N)cr of CF3I/N2 is higher than that of CF3I/CO2 under the same conditions. When the content of CF3I exceeds 20%, the (E/N)cr of CF3I/N2 and CF3I/CO2 gas mixture increase linearly with the increasing of CF3I gas content. The breakdown voltage of CF3I/N2 gas mixture is also higher than that of CF3I/CO2 gas mixture in slightly non-uniform electrical field under power frequency voltage, but the synergistic effect coefficients of the two gas mixtures are basically the same.

  17. Data that empower: The success and promise of CF patient registries.

    PubMed

    Fink, Aliza K; Loeffler, Deena R; Marshall, Bruce C; Goss, Christopher H; Morgan, Wayne J

    2017-11-01

    In this article, we describe existing CF registries with a focus on US registry data collected through the CF Foundation Patient Registry (CFFPR) and the Epidemiologic Study of CF (ESCF); highlight what registries have taught us regarding epidemiology of CF; showcase the impact of registries on research and clinical care; and discuss future directions. This manuscript complements the plenary address given by Dr Wayne Morgan at the 2016 North American CF Conference by summarizing the key points from the presentation and providing additional detail and information. © 2017 Wiley Periodicals, Inc.

  18. CF6 jet engine performance improvement: New fan

    NASA Technical Reports Server (NTRS)

    Fasching, W. A.

    1980-01-01

    As part of the NASA sponsored engine component improvement program, and fan package was developed to reduce fuel consumption in current CF6 turbofan aircraft engine. The new fan package consist of an improved fan blade, reduced fan tip clearance due to a fan case stiffener, and a smooth fan casing tip shroud. CF6 engine performance and acoustic tests demonstrated the predicted 1.8% improvement in cruise sfc without an increase in engine noise. Power management thrust/fan speed characteristics were defined. Mechanical and structural integrity was demonstrated in model fan rotor photoelastic stress tests, full-size fan blade bench fatigue tests, and CF6 engine bird ingestion, crosswind, and cyclic endurance tests. The fan was certified in the CF6-500c2/E2 engines and is in commerical service on the Boeing 747-200, Douglas DC-10-30, and Atrbus industrie A300B aircraft.

  19. Inhibitory effect of polyunsaturated aldehydes (PUAs) on the growth of the toxic benthic dinoflagellate Ostreopsis cf. ovata.

    PubMed

    Pichierri, Salvatore; Pezzolesi, Laura; Vanucci, Silvana; Totti, Cecilia; Pistocchi, Rossella

    2016-10-01

    Diatoms have been shown to produce and release a wide range of secondary metabolites that mediate interactions between individuals of different species. Among these compounds, different types of fatty acid derived long-chained polyunsaturated aldehydes (PUAs) have been related to multiple functions such as intra- or interspecific signals and adverse effect on the reproduction of marine organisms. Several studies have reported changes on growth, cell membrane permeability, flow cytometric properties and cell morphology in phytoplankton organisms exposed to PUAs, but little information is available on the effect of these compounds on benthic microalgae. Ostreopsis cf. ovata is a toxic benthic dinoflagellate which causes massive blooms along the Mediterranean coasts typically during the late summer period. In this study the effects of three toxic PUAs known to be produced by several algae (2E,4E-decadienal, 2E,4E-octadienal and 2E,4E-heptadienal) on the growth, cytological features and cell morphology of O. cf. ovata were investigated. Our results show a clear decrease of O. cf. ovata growth with longer-chain molecules than with shorter-chain ones, confirmed also by EC50 values calculated at 48h for 2E,4E-decadienal and 2E,4E-octadienal (6.6±1.5, 17.9±2.6μmolL(-1) respectively) and at 72h for 2E,4E-heptadienal (18.4±0.7μmolL(-1)). Moreover, morphological analysis highlighted up to 79% of abnormal forms of O. cf. ovata at the highest concentrations of 2E,4E-decadienal tested (9, 18 and 36μmolL(-1)), a gradual DNA degradation and an increase of lipid droplets with all tested PUAs. Further studies are needed to better clarify the interactions between diatoms and O. cf. ovata, especially on bloom-forming dynamics. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Electron attachment to CF{sub 3} and CF{sub 3}Br at temperatures up to 890 K: Experimental test of the kinetic modeling approach

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

    Shuman, Nicholas S.; Miller, Thomas M.; Viggiano, Albert A.

    Thermal rate constants and product branching fractions for electron attachment to CF{sub 3}Br and the CF{sub 3} radical have been measured over the temperature range 300-890 K, the upper limit being restricted by thermal decomposition of CF{sub 3}Br. Both measurements were made in Flowing Afterglow Langmuir Probe apparatuses; the CF{sub 3}Br measurement was made using standard techniques, and the CF{sub 3} measurement using the Variable Electron and Neutral Density Attachment Mass Spectrometry technique. Attachment to CF{sub 3}Br proceeds exclusively by the dissociative channel yielding Br{sup -}, with a rate constant increasing from 1.1 Multiplication-Sign 10{sup -8} cm{sup 3} s{sup -1}more » at 300 K to 5.3 Multiplication-Sign 10{sup -8} cm{sup 3} s{sup -1} at 890 K, somewhat lower than previous data at temperatures up to 777 K. CF{sub 3} attachment proceeds through competition between associative attachment yielding CF{sub 3}{sup -} and dissociative attachment yielding F{sup -}. Prior data up to 600 K showed the rate constant monotonically increasing, with the partial rate constant of the dissociative channel following Arrhenius behavior; however, extrapolation of the data using a recently proposed kinetic modeling approach predicted the rate constant to turn over at higher temperatures, despite being only {approx}5% of the collision rate. The current data agree well with the previous kinetic modeling extrapolation, providing a demonstration of the predictive capabilities of the approach.« less

  1. Atmospheric chemistry of CF3CF═CH2 and (Z)-CF3CF═CHF: Cl and NO3 rate coefficients, Cl reaction product yields, and thermochemical calculations.

    PubMed

    Papadimitriou, Vassileios C; Lazarou, Yannis G; Talukdar, Ranajit K; Burkholder, James B

    2011-01-20

    Rate coefficients, k, for the gas-phase reactions of Cl atoms and NO(3) radicals with 2,3,3,3-tetrafluoropropene, CF(3)CF═CH(2) (HFO-1234yf), and 1,2,3,3,3-pentafluoropropene, (Z)-CF(3)CF═CHF (HFO-1225ye), are reported. Cl-atom rate coefficients were measured in the fall-off region as a function of temperature (220-380 K) and pressure (50-630 Torr; N(2), O(2), and synthetic air) using a relative rate method. The measured rate coefficients are well represented by the fall-off parameters k(0)(T) = 6.5 × 10(-28) (T/300)(-6.9) cm(6) molecule(-2) s(-1) and k(∞)(T) = 7.7 × 10(-11) (T/300)(-0.65) cm(3) molecule(-1) s(-1) for CF(3)CF═CH(2) and k(0)(T) = 3 × 10(-27) (T/300)(-6.5) cm(6) molecule(-2) s(-1) and k(∞)(T) = 4.15 × 10(-11) (T/300)(-0.5) cm(3) molecule(-1) s(-1) for (Z)-CF(3)C═CHF with F(c) = 0.6. Reaction product yields were measured in the presence of O(2) to be (98 ± 7)% for CF(3)C(O)F and (61 ± 4)% for HC(O)Cl in the CF(3)CF═CH(2) reaction and (108 ± 8)% for CF(3)C(O)F and (112 ± 8)% for HC(O)F in the (Z)-CF(3)CF═CHF reaction, where the quoted uncertainties are 2σ (95% confidence level) and include estimated systematic errors. NO(3) reaction rate coefficients were determined using absolute and relative rate methods. Absolute measurements yielded upper limits for both reactions between 233 and 353 K, while the relative rate measurements yielded k(3)(295 K) = (2.6 ± 0.25) × 10(-17) cm(3) molecule(-1) s(-1) and k(4)(295 K) = (4.2 ± 0.5) × 10(-18) cm(3) molecule(-1) s(-1) for CF(3)CF═CH(2) and (Z)-CF(3)CF═CHF, respectively. The Cl-atom reaction with CF(3)CF═CH(2) and (Z)-CF(3)CF═CHF leads to decreases in their atmospheric lifetimes and global warming potentials and formation of a chlorine-containing product, HC(O)Cl, for CF(3)CF═CH(2). The NO(3) reaction has been shown to have a negligible impact on the atmospheric lifetimes of CF(3)CF═CH(2) and (Z)-CF(3)CF═CHF. The energetics for the reaction of Cl, NO(3), and OH with CF

  2. Adult Stem Cell Therapy for Stroke: Challenges and Progress

    PubMed Central

    Bang, Oh Young; Kim, Eun Hee; Cha, Jae Min; Moon, Gyeong Joon

    2016-01-01

    Stroke is one of the leading causes of death and physical disability among adults. It has been 15 years since clinical trials of stem cell therapy in patients with stroke have been conducted using adult stem cells like mesenchymal stem cells and bone marrow mononuclear cells. Results of randomized controlled trials showed that adult stem cell therapy was safe but its efficacy was modest, underscoring the need for new stem cell therapy strategies. The primary limitations of current stem cell therapies include (a) the limited source of engraftable stem cells, (b) the presence of optimal time window for stem cell therapies, (c) inherited limitation of stem cells in terms of growth, trophic support, and differentiation potential, and (d) possible transplanted cell-mediated adverse effects, such as tumor formation. Here, we discuss recent advances that overcome these hurdles in adult stem cell therapy for stroke. PMID:27733032

  3. Deregulation of the growth hormone/insulin-like growth factor-1 axis in adults with cystic fibrosis.

    PubMed

    Pascucci, C; De Biase, R V; Savi, D; Quattrucci, S; Isidori, A M; Lubrano, C; Gnessi, L; Lenzi, A

    2018-05-01

    Patients with cystic fibrosis (CF) present with signs and symptoms that overlap with those of adult growth hormone deficiency (GHD) syndrome: loss of muscle mass, bone fragility and lower stress tolerance. In literature, the prevalence of GHD in pediatric CF patients is higher than general population, but these studies have been performed on children with growth delay. To our knowledge, there are no studies on adult patients. The aim of this paper is to evaluate GH-IGF1 axis in an adult CF population. Fifty clinically stable adult patients, 30 males; age 36 ± 2 years; BMI 21.39 ± 0.22 kg/m 2 and FEV 1 67 ± 4% were studied. Data regarding glycometabolic status and results of pituitary, thyroid, parathyroid, gonadal and adrenal function tests were recorded. All patients underwent a GH releasing hormone (GHRH) + Arginine stimulation test to confirm a GHD. GHRH + Arginine test revealed the presence of GHD in 16 patients (32%); specifically 7 patients had a severe deficiency and 9 a partial deficiency. Adult patients with CF may show GHD. These patients should be followed over time to assess if the GHD could impact the clinical progression of CF.

  4. CF6-6D engine short-term performance deterioration

    NASA Technical Reports Server (NTRS)

    Kramer, W. H.; Paas, J. E.; Smith, J. J.; Wulf, R. H.

    1980-01-01

    Studies conducted as part of the NASA-Lewis CF6 jet engine diagnostics program are summarized. An 82-engine sample of DC-10-10 aircraft engine checkout data that were gathered to define the extent and magnitude of CF6-6D short term performance deterioration were analyzed. These data are substantiated by the performance testing and analytical teardown of CF6-6D short term deterioration engine serial number (ESN) 451507.

  5. Inositol bisphosphate and inositol trisphosphate inhibit cell-to-cell passage of carboxyfluorescein in staminal hairs ofSetcreasea purpurea.

    PubMed

    Tucker, E B

    1988-06-01

    pH-buffered carboxyfluorescein (Buffered-CF) alone (control), or Buffered-CF solutions containing one of the following: (1)D-myo-inositol (I); (2)D-myo-inositol 2-monophosphate (IP1); (3)D-myo-inositol 1,4-bisphosphate (IP2); (4)D-myo-inositol 1,4,5-trisphosphate (IP3); (5)D-fructose 2,6-diphosphate (F-2,6P2) were microinjected into the terminal cells of staminal hairs ofSetcreasea purpurea Boom. Passage of the CF from this terminal cell along the chain of cells towards the filament was monitored for 5 min using fluorescence microscopy and quantified using computer-assisted fluorescence-intensity video analysis. Cell-to-cell transport of CF in hairs microinjected with Buffered-CF containing either I, IP1 or F-2,6P2 was similar to that in hairs microinjected with Buffered-CF only. On the other hand, cell-to-cell transport of CF in hairs microinjected with Buffered-CF containing either IP2 or IP3 was inhibited. These results indicate that polyphosphoinositols may be involved in the regulation of intercellular transport of low-molecular-weight, hydrophilic molecules in plants.

  6. Use of the chloride channel activator lubiprostone for constipation in adults with cystic fibrosis: a case series.

    PubMed

    O'Brien, Catherine E; Anderson, Paula J; Stowe, Cindy D

    2010-03-01

    To describe the use of lubiprostone for constipation in 3 adults with cystic fibrosis (CF). This case series describes the use of lubiprostone for the treatment of constipation in 3 adults with CF (mean +/- SD length of therapy 17.3 +/- 1.5 mo). All 3 patients were prescribed lubiprostone 24 microg twice daily after hospitalization for treatment of intestinal obstruction. Patient 1 continues on chronic polyethylene glycol (PEG) 3350 and lubiprostone and has not had a recurrence of obstruction. Patient 2 requires aggressive chronic therapy with PEG 3350, lubiprostone, and methylnaltrexone. She has had 1 recurrence of obstruction. Patient 3 continues with lubiprostone taken several times per week with good control of constipation and no recurrence of obstruction to date. The adverse effect profile has been tolerable in all 3 patients. CF is caused by a genetic mutation resulting in a dysfunctional or absent CF transmembrane conductance regulator that normally functions as a chloride channel. This results in viscous secretions in multiple organ systems including the lungs and intestinal tract. Accumulation of viscous intestinal contents contributes to constipation, which is common among adults with CF and can sometimes lead to intestinal obstruction. Lubiprostone is indicated for chronic constipation and works by activating type 2 chloride channels (ClC-2) in the intestinal tract. Because it utilizes an alternate chloride channel, lubiprostone may be especially effective for constipation in patients with CF. Lubiprostone provides an additional option for the treatment of constipation in adults with CF. Its use in the CF population deserves further study.

  7. Insights into the degradation of (CF3)2CHOCH3 and its oxidative product (CF3)2CHOCHO & the formation and catalytic degradation of organic nitrates

    NASA Astrophysics Data System (ADS)

    Bai, Feng-Yang; Jia, Zi-Man; Pan, Xiu-Mei

    2018-06-01

    In this work, a systematic investigation of the atmospheric oxidation mechanism of (CF3)2CXOCH3 and their oxidative products (CF3)2CXOCHO (X = H, F) initiated by OH radical or Cl atom is performed by density functional theory. This study reveals that the introduction of NO and O2 promotes the formation of organic nitrates, which are hygroscopic and are inclined to form secondary organic aerosols (SOA) and can affect the air quality. The rate constants of the individual reactions are found to be in agreement with the experimental results. One of the intriguing findings of this work is that the peroxynitrite of (CF3)2CHOCH2OONO formed from the subsequent reactions of (CF3)2CHOCH3 is more favorable to isomerize to organic nitrate (CF3)2CHOCH2ONO2 than to dissociate into alkoxy radical (CF3)2CHOCH2O and NO2 because of the lower energy barrier of isomerization. The second significant observation is that the organic nitrate can be degraded more favorably with the presence of NH3, CH3NH2, and CH3NHCH3 than its naked decomposition reaction (CF3)2CHOCH2ONO2→(CF3)2CHOCHO + HONO. The ammonium salt, a vital part of haze, is harmful to human health and can be formed in the existence of the NH3, CH3NH2, and CH3NHCH3. In addition, the toxic substance of peroxyalkyl nitrate (CF3)2CHOC(O)ONO2 which can reduce the visibility of the atmosphere is produced as the primary subsequent oxidation product of (CF3)2CHOCHO in a NO-rich environment. The main species detected experimentally are confirmed by this study. The computational results are crucial to risk assessment and pollution prevention of the volatile organic compounds (VOCs).

  8. Metabolic alkalosis in adults with stable cystic fibrosis.

    PubMed

    Al-Ghimlas, Fahad; Faughnan, Marie E; Tullis, Elizabeth

    2012-01-01

    The frequency of metabolic alkalosis among adults with stable severe CF-lung disease is unknown. Retrospective chart review. Fourteen CF and 6 COPD (controls) patients were included. FEV1 was similar between the two groups. PaO2 was significantly higher in the COPD (mean ± 2 SD is 72.0 ± 6.8 mmHg,) than in the CF group (56.1 ± 4.1 mmHg). The frequency of metabolic alkalosis in CF patients (12/14, 86%) was significantly greater (p=0.04) than in the COPD group (2/6, 33%). Mixed respiratory acidosis and metabolic alkalosis was evident in 4 CF and 1 COPD patients. Primary metabolic alkalosis was observed in 8 CF and none of the COPD patients. One COPD patient had respiratory and metabolic alkalosis. Metabolic alkalosis is more frequent in stable patients with CF lung disease than in COPD patients. This might be due to defective CFTR function with abnormal electrolyte transport within the kidney and/ or gastrointestinal tract.

  9. Cladosporium fulvum CfHNNI1 induces hypersensitive necrosis, defence gene expression and disease resistance in both host and nonhost plants.

    PubMed

    Cai, Xin-Zhong; Zhou, Xin; Xu, You-Ping; Joosten, Matthieu H A J; de Wit, Pierre J G M

    2007-05-01

    Nonhost resistance as a durable and broad-spectrum defence strategy is of great potential for agricultural applications. We have previously isolated a cDNA showing homology with genes encoding bZIP transcription factors from tomato leaf mould pathogen Cladosporium fulvum. Upon expression, the cDNA results in necrosis in C. fulvum host tomato and nonhost tobacco plants and is thus named CfHNNI1 (for C . f ulvum host and nonhost plant necrosis inducer 1). In the present study we report the induction of necrosis in a variety of nonhost plant species belonging to three families by the transient in planta expression of CfHNNI1 using virus-based vectors. Additionally, transient expression of CfHNNI1 also induced expression of the HR marker gene LeHSR203 and greatly reduced the accumulation of recombinant Potato virus X. Stable CfHNNI1 transgenic tobacco plants were generated in which the expression of CfHNNI1 is under the control of the pathogen-inducible hsr203J promoter. When infected with the oomycetes pathogen Phytophthora parasitica var. nicotianae, these transgenic plants manifested enhanced expression of CfHNNI1 and subsequent accumulation of CfHNNI1 protein, resulting in high expression of the HSR203J and PR genes, and strong resistance to the pathogen. The CfHNNI1 transgenic plants also exhibited induced resistance to Pseudomonas syringae pv. tabaci and Tobacco mosaic virus. Furthermore, CfHNNI1 was highly expressed and the protein was translocated into plant cells during the incompatible interactions between C. fulvum and host and nonhost plants. Our results demonstrate that CfHNNI1 is a potential general elicitor of hypersensitive response and nonhost resistance.

  10. Gastrointestinal Pathology in Juvenile and Adult CFTR-Knockout Ferrets

    PubMed Central

    Sun, Xingshen; Olivier, Alicia K.; Yi, Yaling; Pope, Christopher E.; Hayden, Hillary S.; Liang, Bo; Sui, Hongshu; Zhou, Weihong; Hager, Kyle R.; Zhang, Yulong; Liu, Xiaoming; Yan, Ziying; Fisher, John T.; Keiser, Nicholas W.; Song, Yi; Tyler, Scott R.; Goeken, J. Adam; Kinyon, Joann M.; Radey, Matthew C.; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J.; Kaminsky, Paul M.; Brittnacher, Mitchell J.; Miller, Samuel I.; Parekh, Kalpaj; Meyerholz, David K.; Hoffman, Lucas R.; Frana, Timothy; Stewart, Zoe A.; Engelhardt, John F.

    2015-01-01

    Cystic fibrosis (CF) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in many epithelia of the body. Here we report the pathology observed in the gastrointestinal organs of juvenile to adult CFTR-knockout ferrets. CF gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. Metagenomic phylogenetic analysis of fecal microbiota by deep sequencing revealed considerable genotype-independent microbial diversity between animals, with the majority of taxa overlapping between CF and non-CF pairs. CF hepatic manifestations were variable, but included steatosis, necrosis, biliary hyperplasia, and biliary fibrosis. Gallbladder cystic mucosal hyperplasia was commonly found in 67% of CF animals. The majority of CF animals (85%) had pancreatic abnormalities, including extensive fibrosis, loss of exocrine pancreas, and islet disorganization. Interestingly, 2 of 13 CF animals retained predominantly normal pancreatic histology (84% to 94%) at time of death. Fecal elastase-1 levels from these CF animals were similar to non-CF controls, whereas all other CF animals evaluated were pancreatic insufficient (<2 μg elastase-1 per gram of feces). These findings suggest that genetic factors likely influence the extent of exocrine pancreas disease in CF ferrets and have implications for the etiology of pancreatic sufficiency in CF patients. In summary, these studies demonstrate that the CF ferret model develops gastrointestinal pathology similar to CF patients. PMID:24637292

  11. Identification and isolation of adult liver stem/progenitor cells.

    PubMed

    Tanaka, Minoru; Miyajima, Atsushi

    2012-01-01

    Hepatoblasts are considered to be liver stem/progenitor cells in the fetus because they propagate and differentiate into two types of liver epithelial cells, hepatocytes and cholangiocytes. In adults, oval cells that emerge in severely injured liver are considered facultative hepatic stem/progenitor cells. However, the nature of oval cells has remained unclear for long time due to the lack of a method to isolate them. It has also been unclear whether liver stem/progenitor cells exist in normal adult liver. Recently, we and others have successfully identified oval cells and adult liver stem/progenitor cells. Here, we describe the identification and isolation of mouse liver stem/progenitor cells by utilizing antibodies against specific cell surface marker molecules.

  12. [Early aseptic loosening of the CF 30 femoral stem].

    PubMed

    Kovanda, M; Havlícek, V; Hudec, J

    2007-02-01

    The CF 30 stem in combination with a cementless acetabulum was used at the First Department of Orthopedic Surgery in Brno in the years 1994 to 1995. From the second year following implantation, aseptic stem loosening was recorded. In order to find explanation of this early loosening, the authors, in cooperation with the Institute of Solid Mechanics, Mechatronics and Biomechanics, carried out the stress-strain analysis in a model system. Eighty patients (31 men and 49 women) received a cemented CF30 femoral component in 1994. Of them, 16 patients underwent revision arthroplasty, three died of causes unrelated to the surgery, and four were lost to follow-up. The final clinical and radiographic check-up was carried out in 2001. The results of a comprehensive examination were available in 57 patients with a CF30 stem. The patients were evaluated on the basis of the Harris hip score and anteroposterior radiographs of the hip. X-ray films obtained immediately after surgery and those taken at regular intervals during follow-up were compared. The following characteristics were noted: translucent lines in individual zones along the stem at the cement-bone interface; osteolysis, i. e., non-linear translucent areas, at least 5 mm long, at the cement-bone interface; and subsidence of the femoral component, i. e., migration of the stem distal to the tip of the greater trochanter. The CF 30 stem survival curve showed that aseptic stem loosening occurred from post-implantation year 2, and increased during the following years. At 6 years and 6 months, a total of 16 patients underwent revision surgery, involving reimplantation in 14 and implant removal in 2 patients. Potential causes of aseptic loosening: Polyethylene wear.However, no acetabular loosening was found in this group, although acetabular components are reported to become loose more often than femoral components. By comparison of the stem survival curves for Poldi and CF 30 stems it appeared that, at 6 years and 6 months

  13. Lung phenotype of juvenile and adult cystic fibrosis transmembrane conductance regulator-knockout ferrets.

    PubMed

    Sun, Xingshen; Olivier, Alicia K; Liang, Bo; Yi, Yaling; Sui, Hongshu; Evans, Turan I A; Zhang, Yulong; Zhou, Weihong; Tyler, Scott R; Fisher, John T; Keiser, Nicholas W; Liu, Xiaoming; Yan, Ziying; Song, Yi; Goeken, J Adam; Kinyon, Joann M; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J; Kaminsky, Paul M; Stewart, Zoe A; Pope, R Marshall; Frana, Timothy; Meyerholz, David K; Parekh, Kalpaj; Engelhardt, John F

    2014-03-01

    Chronic bacterial lung infections in cystic fibrosis (CF) are caused by defects in the CF transmembrane conductance regulator chloride channel. Previously, we described that newborn CF transmembrane conductance regulator-knockout ferrets rapidly develop lung infections within the first week of life. Here, we report a more slowly progressing lung bacterial colonization phenotype observed in juvenile to adult CF ferrets reared on a layered antibiotic regimen. Even on antibiotics, CF ferrets were still very susceptible to bacterial lung infection. The severity of lung histopathology ranged from mild to severe, and variably included mucus obstruction of the airways and submucosal glands, air trapping, atelectasis, bronchopneumonia, and interstitial pneumonia. In all CF lungs, significant numbers of bacteria were detected and impaired tracheal mucociliary clearance was observed. Although Streptococcus, Staphylococcus, and Enterococcus were observed most frequently in the lungs of CF animals, each animal displayed a predominant bacterial species that accounted for over 50% of the culturable bacteria, with no one bacterial taxon predominating in all animals. Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry fingerprinting was used to quantify lung bacteria in 10 CF animals and demonstrated Streptococcus, Staphylococcus, Enterococcus, or Escherichia as the most abundant genera. Interestingly, there was significant overlap in the types of bacteria observed in the lung and intestine of a given CF animal, including bacterial taxa unique to the lung and gut of each CF animal analyzed. These findings demonstrate that CF ferrets develop lung disease during the juvenile and adult stages that is similar to patients with CF, and suggest that enteric bacterial flora may seed the lung of CF ferrets.

  14. Lung Phenotype of Juvenile and Adult Cystic Fibrosis Transmembrane Conductance Regulator–Knockout Ferrets

    PubMed Central

    Sun, Xingshen; Olivier, Alicia K.; Liang, Bo; Yi, Yaling; Sui, Hongshu; Evans, Turan I. A.; Zhang, Yulong; Zhou, Weihong; Tyler, Scott R.; Fisher, John T.; Keiser, Nicholas W.; Liu, Xiaoming; Yan, Ziying; Song, Yi; Goeken, J. Adam; Kinyon, Joann M.; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J.; Kaminsky, Paul M.; Stewart, Zoe A.; Pope, R. Marshall; Frana, Timothy; Meyerholz, David K.; Parekh, Kalpaj

    2014-01-01

    Chronic bacterial lung infections in cystic fibrosis (CF) are caused by defects in the CF transmembrane conductance regulator chloride channel. Previously, we described that newborn CF transmembrane conductance regulator–knockout ferrets rapidly develop lung infections within the first week of life. Here, we report a more slowly progressing lung bacterial colonization phenotype observed in juvenile to adult CF ferrets reared on a layered antibiotic regimen. Even on antibiotics, CF ferrets were still very susceptible to bacterial lung infection. The severity of lung histopathology ranged from mild to severe, and variably included mucus obstruction of the airways and submucosal glands, air trapping, atelectasis, bronchopneumonia, and interstitial pneumonia. In all CF lungs, significant numbers of bacteria were detected and impaired tracheal mucociliary clearance was observed. Although Streptococcus, Staphylococcus, and Enterococcus were observed most frequently in the lungs of CF animals, each animal displayed a predominant bacterial species that accounted for over 50% of the culturable bacteria, with no one bacterial taxon predominating in all animals. Matrix-assisted laser desorption–ionization time-of-flight mass spectrometry fingerprinting was used to quantify lung bacteria in 10 CF animals and demonstrated Streptococcus, Staphylococcus, Enterococcus, or Escherichia as the most abundant genera. Interestingly, there was significant overlap in the types of bacteria observed in the lung and intestine of a given CF animal, including bacterial taxa unique to the lung and gut of each CF animal analyzed. These findings demonstrate that CF ferrets develop lung disease during the juvenile and adult stages that is similar to patients with CF, and suggest that enteric bacterial flora may seed the lung of CF ferrets. PMID:24074402

  15. Incidence and clinical impact of respiratory viruses in adults with cystic fibrosis.

    PubMed

    Flight, William G; Bright-Thomas, Rowland J; Tilston, Peter; Mutton, Kenneth J; Guiver, Malcolm; Morris, Julie; Webb, A Kevin; Jones, Andrew M

    2014-03-01

    Viral respiratory infection (VRI) is a common cause of pulmonary exacerbations in children with cystic fibrosis (CF). The importance of VRI in adult CF populations is unclear. To determine the incidence and clinical impact of VRI among adults with CF. One hundred adults with CF were followed up prospectively for 12 months. Sputum, nose swabs and throat swabs were collected every 2 months and at onset of pulmonary exacerbation. PCR assays for adenovirus, influenza A&B, human metapneumovirus, parainfluenza 1-3, respiratory syncytial virus and human rhinovirus were performed on each sample. Symptom scores, spirometry and inflammatory markers were measured at each visit. One or more respiratory viruses were detected in 191/626 (30.5%) visits. Human rhinovirus accounted for 72.5% of viruses. Overall incidence of VRI was 1.66 (95% CI 1.39 to 1.92) cases/patient-year. VRI was associated with increased risk of pulmonary exacerbation (OR=2.19; 95% CI 1.56 to 3.08; p<0.001) and prescription of antibiotics (OR=2.26; 95% CI 1.63 to 3.13; p<0.001). Virus-positive visits were associated with higher respiratory symptom scores and greater C-reactive protein levels. Virus-positive exacerbations had a lower acute fall in FEV1 than virus-negative exacerbations (12.7% vs 15.6%; p=0.040). The incidence of exacerbations, but not VRI, was associated with greater lung function decline over 12 months (-1.79% per pulmonary exacerbation/year; 95% CI -3.4 to -0.23; p=0.025). VRI is common in adults with CF and is associated with substantial morbidity. Respiratory viruses are a potential therapeutic target in CF lung disease.

  16. Assessment of the atmospheric loss processes initiated by OH radicals and sunlight, and the radiative efficiency for a series of hydrofluoroolefins, CF3(CF2)x=1,3,5CHCH2.

    PubMed

    González, Sergio; Jiménez, Elena; Albaladejo, José

    2016-05-01

    Hydrofluoroolefins (HFOs) of the type CF3(CF2)x≥0CHCH2, are currently being suggested as substitutes of some hydrofluorocarbons (HFCs). In this work, an assessment of the atmospheric removal of CF3(CF2)x=1,3,5CHCH2, initiated by reaction with hydroxyl (OH) radicals and UV solar radiation is addressed. For that purpose, the rate coefficients for the OH + CF3(CF2)x=1,3,5CHCH2 reaction, kOH(T = 263-358 K), were determined by the pulsed laser photolysis-laser induced fluorescence technique. A slightly negative temperature dependence of kOH was observed, obtaining Ea/R (in K) values of -124 ± 15, -128 ± 6 and -160 ± 10, for CF3CF2CHCH2, CF3(CF2)3CHCH2 and CF3(CF2)5CHCH2, respectively. The estimated atmospheric lifetimes are around 8 days, considering that HFOs are well-mixed in the troposphere. Furthermore, an evaluation of the long-wave and short-wave absorption process of these HFOs have been carried out by determining the UV (191-367 nm) and IR (4000-500 cm(-1)) absorption cross sections at 298 K. Based on the obtained UV absorption cross sections, no photolysis of CF3(CF2)x=1,3,5CHCH2 is expected in the troposphere (λ > 290 nm). These species strongly absorb IR radiation in the atmospheric IR window. Despite the strong absorption in the IR region, the lifetime corrected radiative efficiencies are low (0.033 W m(-2) ppb(-1) for CF3(CF2)3CHCH2 and 0.039 Wm(-2) ppb(-1) for CF3(CF2)5CHCH2). Calculation of GWPs for these species has been performed as a function of the horizon time, providing values higher than unity for a short-period term, decreasing dramatically for longer periods. Therefore, it is concluded that emissions of these species do not affect the radiative forcing of climate, making them suitable replacements of large-GWP HFCs. Copyright © 2016. Published by Elsevier Ltd.

  17. Transepithelial nasal potential difference (NPD) measurements in cystic fibrosis (CF).

    PubMed

    Sands, Dorota

    2013-01-01

    The main underlying physiologic abnormality in cystic fibrosis (CF) is dysfunction of the CF transmembrane conductance regulator (CFTR), which results in abnormal transport of sodium and chloride across epithelial surfaces. CFTR function could be tested in vivo using measurements of nasal transepithelial potential difference (PD). Nasal measurements show characteristic features of CF epithelia, including hyperpolarized baseline readings (basal PD), excessive depolarization in response to sodium channel inhibitors, such as amiloride (ΔAmiloride), and little or no chloride (Cl-) secretion in response to isoproterenol in a chloride-free solution (ΔCl- free-isoproterenol). PD test is applied for CF diagnosis and monitoring of new therapeutic modulations and corrections.

  18. The CF6 engine performance improvement

    NASA Technical Reports Server (NTRS)

    Fasching, W. A.

    1982-01-01

    As part of the NASA-sponsored Engine Component Improvement (ECI) Program, a feasibility analysis of performance improvement and retention concepts for the CF6-6 and CF6-50 engines was conducted and seven concepts were identified for development and ground testing: new fan, new front mount, high pressure turbine aerodynamic performance improvement, high pressure turbine roundness, high pressure turbine active clearance control, low pressure turbine active clearance control, and short core exhaust nozzle. The development work and ground testing are summarized, and the major test results and an enomic analysis for each concept are presented.

  19. Overexpression of a novel Arabidopsis PP2C isoform, AtPP2CF1, enhances plant biomass production by increasing inflorescence stem growth.

    PubMed

    Sugimoto, Hiroki; Kondo, Satoshi; Tanaka, Tomoko; Imamura, Chie; Muramoto, Nobuhiko; Hattori, Etsuko; Ogawa, Ken'ichi; Mitsukawa, Norihiro; Ohto, Chikara

    2014-10-01

    In contrast to mammals, higher plants have evolved to express diverse protein phosphatase 2Cs (PP2Cs). Of all Arabidopsis thaliana PP2Cs, members of PP2C subfamily A, including ABI1, have been shown to be key negative regulators of abscisic acid (ABA) signalling pathways, which regulate plant growth and development as well as tolerance to adverse environmental conditions. However, little is known about the enzymatic and signalling roles of other PP2C subfamilies. Here, we report a novel Arabidopsis subfamily E PP2C gene, At3g05640, designated AtPP2CF1. AtPP2CF1 was dramatically expressed in response to exogenous ABA and was expressed in vascular tissues and guard cells, similar to most subfamily A PP2C genes. In vitro enzymatic activity assays showed that AtPP2CF1 possessed functional PP2C activity. However, yeast two-hybrid analysis revealed that AtPP2CF1 did not interact with PYR/PYL/RCAR receptors or three SnRK2 kinases, which are ABI1-interacting proteins. This was supported by homology-based structural modelling demonstrating that the putative active- and substrate-binding site of AtPP2CF1 differed from that of ABI1. Furthermore, while overexpression of ABI1 in plants induced an ABA-insensitive phenotype, Arabidopsis plants overexpressing AtPP2CF1 (AtPP2CF1oe) were weakly hypersensitive to ABA during seed germination and drought stress. Unexpectedly, AtPP2CF1oe plants also exhibited increased biomass yield, mainly due to accelerated growth of inflorescence stems through the activation of cell proliferation and expansion. Our results provide new insights into the physiological significance of AtPP2CF1 as a candidate gene for plant growth production and for potential application in the sustainable supply of plant biomass. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Overexpression of a novel Arabidopsis PP2C isoform, AtPP2CF1, enhances plant biomass production by increasing inflorescence stem growth

    PubMed Central

    Sugimoto, Hiroki; Kondo, Satoshi; Tanaka, Tomoko; Imamura, Chie; Muramoto, Nobuhiko; Hattori, Etsuko; Ogawa, Ken’ichi; Mitsukawa, Norihiro; Ohto, Chikara

    2014-01-01

    In contrast to mammals, higher plants have evolved to express diverse protein phosphatase 2Cs (PP2Cs). Of all Arabidopsis thaliana PP2Cs, members of PP2C subfamily A, including ABI1, have been shown to be key negative regulators of abscisic acid (ABA) signalling pathways, which regulate plant growth and development as well as tolerance to adverse environmental conditions. However, little is known about the enzymatic and signalling roles of other PP2C subfamilies. Here, we report a novel Arabidopsis subfamily E PP2C gene, At3g05640, designated AtPP2CF1. AtPP2CF1 was dramatically expressed in response to exogenous ABA and was expressed in vascular tissues and guard cells, similar to most subfamily A PP2C genes. In vitro enzymatic activity assays showed that AtPP2CF1 possessed functional PP2C activity. However, yeast two-hybrid analysis revealed that AtPP2CF1 did not interact with PYR/PYL/RCAR receptors or three SnRK2 kinases, which are ABI1-interacting proteins. This was supported by homology-based structural modelling demonstrating that the putative active- and substrate-binding site of AtPP2CF1 differed from that of ABI1. Furthermore, while overexpression of ABI1 in plants induced an ABA-insensitive phenotype, Arabidopsis plants overexpressing AtPP2CF1 (AtPP2CF1oe) were weakly hypersensitive to ABA during seed germination and drought stress. Unexpectedly, AtPP2CF1oe plants also exhibited increased biomass yield, mainly due to accelerated growth of inflorescence stems through the activation of cell proliferation and expansion. Our results provide new insights into the physiological significance of AtPP2CF1 as a candidate gene for plant growth production and for potential application in the sustainable supply of plant biomass. PMID:25038254

  1. A Cross-Sectional Study of the Psychological Needs of Adults Living with Cystic Fibrosis

    PubMed Central

    Pakhale, Smita; Baron, Justine; Armstrong, Michael; Tasca, Georgio; Gaudet, Ena; Aaron, Shawn; Cameron, William; Balfour, Louise

    2015-01-01

    Background Depression and anxiety are prevalent in people with cystic fibrosis (CF), yet psychological services are rarely accessible in CF clinics. This cross-sectional single center study reports on a psychological needs assessment of people with CF. Methods We asked adults attending a CF clinic, without integrated psychological services, to complete a psychological needs assessment survey that included items on: a) past access to psychological services (via a CF referral service), b) concerns relevant to discuss with a psychologist, and c) their likelihood of accessing psychological services if available at the CF clinic, and standardized measures of depression (CES-D) and anxiety (GAD-7). Results We enrolled 49 participants and 45 (91.8%) completed the survey. Forty percent reported elevated symptoms of depression and 13% had elevated anxiety. A majority of individuals (72.2% and 83.3%, respectively) indicated they would be likely to use psychological services, if available at the clinic. Concerns considered most relevant to discuss with a psychologist were: 1) worries (51.1%), 2) mood (44.4%), 3) life stress (46.6%), 4) adjustment to CF (42.2%), 5) life transitions (42.2%) and 6) quality of life (42.2%). Conclusions This study highlights the rationale for screening adults with CF for depression and anxiety, and to facilitate provision of psychological services and preventative mental health interventions as an integral component of multi-disciplinary CF care. PMID:26102351

  2. Primary Cell Culture of Live Neurosurgically Resected Aged Adult Human Brain Cells and Single Cell Transcriptomics.

    PubMed

    Spaethling, Jennifer M; Na, Young-Ji; Lee, Jaehee; Ulyanova, Alexandra V; Baltuch, Gordon H; Bell, Thomas J; Brem, Steven; Chen, H Isaac; Dueck, Hannah; Fisher, Stephen A; Garcia, Marcela P; Khaladkar, Mugdha; Kung, David K; Lucas, Timothy H; O'Rourke, Donald M; Stefanik, Derek; Wang, Jinhui; Wolf, John A; Bartfai, Tamas; Grady, M Sean; Sul, Jai-Yoon; Kim, Junhyong; Eberwine, James H

    2017-01-17

    Investigation of human CNS disease and drug effects has been hampered by the lack of a system that enables single-cell analysis of live adult patient brain cells. We developed a culturing system, based on a papain-aided procedure, for resected adult human brain tissue removed during neurosurgery. We performed single-cell transcriptomics on over 300 cells, permitting identification of oligodendrocytes, microglia, neurons, endothelial cells, and astrocytes after 3 weeks in culture. Using deep sequencing, we detected over 12,000 expressed genes, including hundreds of cell-type-enriched mRNAs, lncRNAs and pri-miRNAs. We describe cell-type- and patient-specific transcriptional hierarchies. Single-cell transcriptomics on cultured live adult patient derived cells is a prime example of the promise of personalized precision medicine. Because these cells derive from subjects ranging in age into their sixties, this system permits human aging studies previously possible only in rodent systems. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Allogenic fetal liver cells have a distinct competitive engraftment advantage over adult bone marrow cells when infused into fetal as compared with adult severe combined immunodeficient recipients.

    PubMed

    Taylor, Patricia A; McElmurry, Ronald T; Lees, Christopher J; Harrison, David E; Blazar, Bruce R

    2002-03-01

    In utero transplantation (IUT) is becoming a viable option for the treatment of various immune and metabolic disorders diagnosed early in gestation. In this study, donor fetal liver cells had a 10-fold competitive engraftment advantage relative to adult bone marrow in allogeneic fetal severe combined immunodeficient (SCID) recipients compared with adult recipients. In contrast, adult bone marrow cells engrafted slightly better than fetal liver cells in allogeneic adult SCID transplant recipients. By using different ratios of fetal and adult cell mixtures, fetal liver cells repopulated 8.2 times better than adult bone marrow cells in fetal recipients, but only 0.8 times as well in adult recipients. Fetal SCID recipients were more permissive to an allogeneic donor graft than adult recipients. These data indicate that the recipient microenvironment may regulate the engraftment efficiency of a given stem cell source and suggest that the use of cord blood should be tested in clinical IUT.

  4. Gastrointestinal pathology in juvenile and adult CFTR-knockout ferrets.

    PubMed

    Sun, Xingshen; Olivier, Alicia K; Yi, Yaling; Pope, Christopher E; Hayden, Hillary S; Liang, Bo; Sui, Hongshu; Zhou, Weihong; Hager, Kyle R; Zhang, Yulong; Liu, Xiaoming; Yan, Ziying; Fisher, John T; Keiser, Nicholas W; Song, Yi; Tyler, Scott R; Goeken, J Adam; Kinyon, Joann M; Radey, Matthew C; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J; Kaminsky, Paul M; Brittnacher, Mitchell J; Miller, Samuel I; Parekh, Kalpaj; Meyerholz, David K; Hoffman, Lucas R; Frana, Timothy; Stewart, Zoe A; Engelhardt, John F

    2014-05-01

    Cystic fibrosis (CF) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in many epithelia of the body. Here we report the pathology observed in the gastrointestinal organs of juvenile to adult CFTR-knockout ferrets. CF gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. Metagenomic phylogenetic analysis of fecal microbiota by deep sequencing revealed considerable genotype-independent microbial diversity between animals, with the majority of taxa overlapping between CF and non-CF pairs. CF hepatic manifestations were variable, but included steatosis, necrosis, biliary hyperplasia, and biliary fibrosis. Gallbladder cystic mucosal hyperplasia was commonly found in 67% of CF animals. The majority of CF animals (85%) had pancreatic abnormalities, including extensive fibrosis, loss of exocrine pancreas, and islet disorganization. Interestingly, 2 of 13 CF animals retained predominantly normal pancreatic histology (84% to 94%) at time of death. Fecal elastase-1 levels from these CF animals were similar to non-CF controls, whereas all other CF animals evaluated were pancreatic insufficient (<2 μg elastase-1 per gram of feces). These findings suggest that genetic factors likely influence the extent of exocrine pancreas disease in CF ferrets and have implications for the etiology of pancreatic sufficiency in CF patients. In summary, these studies demonstrate that the CF ferret model develops gastrointestinal pathology similar to CF patients. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  5. Repurposing tromethamine as inhaled therapy to treat CF airway disease

    PubMed Central

    Alaiwa, Mahmoud H. Abou; Launspach, Janice L.; Sheets, Kelsey A.; Rivera, Jade A.; Gansemer, Nicholas D.; Taft, Peter J.; Thorne, Peter S.; Welsh, Michael J.; Stoltz, David A.

    2016-01-01

    In cystic fibrosis (CF), loss of CF transmembrane conductance regulator (CFTR) anion channel activity causes airway surface liquid (ASL) pH to become acidic, which impairs airway host defenses. One potential therapeutic approach is to correct the acidic pH in CF airways by aerosolizing HCO3– and/or nonbicarbonate pH buffers. Here, we show that raising ASL pH with inhaled HCO3– increased pH. However, the effect was transient, and pH returned to baseline values within 30 minutes. Tromethamine (Tham) is a buffer with a long serum half-life used as an i.v. formulation to treat metabolic acidosis. We found that Tham aerosols increased ASL pH in vivo for at least 2 hours and enhanced bacterial killing. Inhaled hypertonic saline (7% NaCl) is delivered to people with CF in an attempt to promote mucus clearance. Because an increased ionic strength inhibits ASL antimicrobial factors, we added Tham to hypertonic saline and applied it to CF sputum. We found that Tham alone and in combination with hypertonic saline increased pH and enhanced bacterial killing. These findings suggest that aerosolizing the HCO3–-independent buffer Tham, either alone or in combination with hypertonic saline, might be of therapeutic benefit in CF airway disease. PMID:27390778

  6. Anxiety and depression in adults with cystic fibrosis: a comparison between patients and the general population in Sweden and three other European countries.

    PubMed

    Backström-Eriksson, Lena; Sorjonen, Kimmo; Bergsten-Brucefors, Agneta; Hjelte, Lena; Melin, Bo

    2015-10-14

    Cystic fibrosis (CF) is the most common autosomal recessive life-shortening disease among Caucasians. Studies exploring the prevalence of anxiety and depression in adult CF patients are few, show inconsistent findings and rarely include comparisons with general populations. Prevalence and degree of anxiety and depression were investigated in adult CF patients in Sweden, Belgium, Germany and the UK, and compared to corresponding general population data. Adult non-transplanted CF patients from the three largest CF-centres (out of four) in Sweden (N = 129; Age range 18-70 years; 50 % women) completed the Hospital Anxiety and Depression Scale (HADS). Studies using HADS in adult CF populations in the UK, Germany, and Belgium were included, as well as HADS normative data from the corresponding general populations. No elevated risk for anxiety and depression was found among the CF patients. However, a Country x Group interaction effect emerged; CF patients experienced a higher degree of anxiety than the general population in Sweden, but not in the other countries, though this finding did not remain significant in a logistic regression analysis. In Sweden the effect was limited to women. A Country x Group interaction effect was also found for Depression; CF patients experienced lower degree of depression than the general population in Sweden, Germany and the UK, but not in Belgium/Netherlands. Contrary to earlier outcomes, the present results do not indicate any general elevated risk for anxiety and depression among CF patients. Anxiety was slightly higher in the Swedish CF population, compared to the general population; this finding was not seen in the other countries. Depression among CF patients was lower than or similar to that in the general populations in the studied countries.

  7. Concise Review: Adult Mesenchymal Stem Cells, Adult Neural Crest Stem Cells, and Therapy of Neurological Pathologies: A State of Play

    PubMed Central

    Neirinckx, Virginie; Coste, Cécile; Rogister, Bernard

    2013-01-01

    Adult stem cells are endowed with in vitro multilineage differentiation abilities and constitute an attractive autologous source of material for cell therapy in neurological disorders. With regard to lately published results, the ability of adult mesenchymal stem cells (MSCs) and neural crest stem cells (NCSCs) to integrate and differentiate into neurons once inside the central nervous system (CNS) is currently questioned. For this review, we collected exhaustive data on MSC/NCSC neural differentiation in vitro. We then analyzed preclinical cell therapy experiments in different models for neurological diseases and concluded that neural differentiation is probably not the leading property of adult MSCs and NCSCs concerning neurological pathology management. A fine analysis of the molecules that are secreted by MSCs and NCSCs would definitely be of significant interest regarding their important contribution to the clinical and pathological recovery after CNS lesions. PMID:23486833

  8. Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later

    PubMed Central

    Bond, Allison M.; Ming, Guo-li; Song, Hongjun

    2015-01-01

    Summary Adult somatic stem cells in various organs maintain homeostatic tissue regeneration and enhance plasticity. Since its initial discovery five decades ago, investigations of adult neurogenesis and neural stem cells have led to an established and expanding field that has significantly influenced many facets of neuroscience, developmental biology and regenerative medicine. Here we review recent progress and focus on questions related to adult mammalian neural stem cells that also apply to other somatic stem cells. We further discuss emerging topics that are guiding the field toward better understanding adult neural stem cells and ultimately applying these principles to improve human health. PMID:26431181

  9. Summary report for CF6 jet engine diagnostics program

    NASA Technical Reports Server (NTRS)

    Fasching, W. A.; Stricklin, R.

    1982-01-01

    Cockpit cruise recordings and test cell data in conjunction with hardware inspection results from airline overhaul shops were analyzed to define the extent and magnitude of performance deterioration of the General Electric CF6 high bypass turbofan engines. The magnitude of Short Term deterioration from the Long Term was isolated and the individual damage mechanisms that were the cause for the majority of the performance deterioration were identified. A potential for reduction in compressor clearance and a potential for improvement in turbine roundness, which corresponds to cruise SFC reductions of 0.38 and 0.36 percent, respectively, were identified.

  10. Metabolic Alkalosis in Adults with Stable Cystic Fibrosis

    PubMed Central

    Al-Ghimlas, Fahad; Faughnan, Marie E; Tullis, Elizabeth

    2012-01-01

    Background: The frequency of metabolic alkalosis among adults with stable severe CF-lung disease is unknown. Methods: Retrospective chart review. Results: Fourteen CF and 6 COPD (controls) patients were included. FEV1 was similar between the two groups. PaO2 was significantly higher in the COPD (mean ± 2 SD is 72.0 ± 6.8 mmHg,) than in the CF group (56.1 ± 4.1 mmHg). The frequency of metabolic alkalosis in CF patients (12/14, 86%) was significantly greater (p=0.04) than in the COPD group (2/6, 33%). Mixed respiratory acidosis and metabolic alkalosis was evident in 4 CF and 1 COPD patients. Primary metabolic alkalosis was observed in 8 CF and none of the COPD patients. One COPD patient had respiratory and metabolic alkalosis. Conclusions: Metabolic alkalosis is more frequent in stable patients with CF lung disease than in COPD patients. This might be due to defective CFTR function with abnormal electrolyte transport within the kidney and/ or gastrointestinal tract. PMID:22905070

  11. Chromosome aberrations in T lymphocytes carrying adult T-cell leukemia-associated antigens (ATLA) from healthy adults.

    PubMed

    Fukuhara, S; Hinuma, Y; Gotoh, Y I; Uchino, H

    1983-01-01

    Chromosomes were studied in cultured T lymphocytes carrying adult T-cell leukemia-associated antigens (ATLA) that were obtained from five Japanese anti-ATLA seropositive healthy adults. Chromosomally abnormal cells were observed in three of the five healthy adults, and these cells were clonal in two subjects. All cells examined in one subject had rearrangements of chromosome nos. 7 and 14. Clonal cells from the second had a minute chromosome of unknown origin. A few cells in the third had nonclonal rearrangements of chromosomes. Thus, ATLA-positive T lymphocytes in some anti-ATLA seropositive healthy people have chromosome aberrations.

  12. Intestinal stem cells in the adult Drosophila midgut

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

    Jiang, Huaqi, E-mail: Huaqi.Jiang@UTSouthwestern.edu; Edgar, Bruce A., E-mail: b.edgar@dkfz.de; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights:more » Black-Right-Pointing-Pointer The homeostasis and regeneration of adult fly midguts are mediated by ISCs. Black-Right-Pointing-Pointer Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). Black-Right-Pointing-Pointer EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. Black-Right-Pointing-Pointer Notch signaling regulates ISC self-renewal and differentiation.« less

  13. NetCDF-CF: Supporting Earth System Science with Data Access, Analysis, and Visualization

    NASA Astrophysics Data System (ADS)

    Davis, E.; Zender, C. S.; Arctur, D. K.; O'Brien, K.; Jelenak, A.; Santek, D.; Dixon, M. J.; Whiteaker, T. L.; Yang, K.

    2017-12-01

    NetCDF-CF is a community-developed convention for storing and describing earth system science data in the netCDF binary data format. It is an OGC recognized standard with numerous existing FOSS (Free and Open Source Software) and commercial software tools can explore, analyze, and visualize data that is stored and described as netCDF-CF data. To better support a larger segment of the earth system science community, a number of efforts are underway to extend the netCDF-CF convention with the goal of increasing the types of data that can be represented as netCDF-CF data. This presentation will provide an overview and update of work to extend the existing netCDF-CF convention. It will detail the types of earth system science data currently supported by netCDF-CF and the types of data targeted for support by current netCDF-CF convention development efforts. It will also describe some of the tools that support the use of netCDF-CF compliant datasets, the types of data they support, and efforts to extend them to handle the new data types that netCDF-CF will support.

  14. From children to young adults: cystic fibrosis and siblingship: a longitudinal study.

    PubMed

    Wennström, I L; Isberg, P E; Wirtberg, I; Rydén, O

    2011-07-01

    To compare the results from our previous study in 1994/95 of children with cystic fibrosis (CF) at the age of 6-14 years and their healthy siblings with data from the same participants as young adults in regard to their self-esteem, life satisfaction and attitudes towards the CF siblingship situation. Thirty-seven sibling pairs participated. Three instruments were used: The 'As I see myself' self-evaluation questionnaire; the 'Ladder of life', assessing life satisfaction; and the 'Sibling Mirror', reflecting a person's feelings, when one's sibling or oneself has CF. Contrary to 1994/95 study results, the female participants showed no signs of impaired self-esteem. Concerning life satisfaction, women in both groups and the men with CF have lower ratings than a healthy reference group. Individuals with CF look upon themselves today as independent, thoughtful and mature, but remember themselves as being active, spoiled or fussy. Healthy siblings consider themselves diplomatic, responsible, mature, important and loyal but remember themselves as angry, envious and neglected.  The self-esteem of women in the sibling pairs (whether with CF or healthy sisters) has improved since their childhood. Overall, the results indicate that young adults with CF today are medically well controlled and psychosocially well adapted, albeit aware of their precarious future. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

  15. Cockpit Accommodation Assessment of the Bell 412CF Helicopter (Evaluation du Poste de Pilotage de l’Hellcoptere Bell 412CF)

    DTIC Science & Technology

    2009-12-01

    Research, Ottawa , 1998 as issued jointly by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada...Flight Rules ) skills. Nine Bell 412CF helicopters were produced from existing CH-146 Griffons, which posed technical challenges. One such compromise was...IFR (Instrument Flight Rules ) skills. Nine Bell 412CF helicopters were produced from existing CH-146 Griffons, which posed technical challenges. One

  16. Impact of the increased adoption of prenatal cfDNA screening on non-profit patient advocacy organizations in the United States.

    PubMed

    Meredith, Stephanie; Kaposy, Christopher; Miller, Victoria J; Allyse, Megan; Chandrasekharan, Subhashini; Michie, Marsha

    2016-08-01

    The 'Stakeholder Perspectives on Noninvasive Prenatal Genetic Screening' Symposium was held in conjunction with the 2015 annual meeting of the International Society for Prenatal Diagnosis. During the day-long meeting, a panel of patient advocacy group (PAG) representatives discussed concerns and challenges raised by prenatal cell-free DNA (cfDNA) screening, which has resulted in larger demands upon PAGs from concerned patients receiving prenatal cfDNA screening results. Prominent concerns included confusion about the accuracy of cfDNA screening and a lack of patient education resources about genetic conditions included in cfDNA screens. Some of the challenges faced by PAGs included funding limitations, lack of consistently implemented standards of care and oversight, diverse perspectives among PAGs and questions about neutrality, and lack of access to training and genetic counselors. PAG representatives also put forward suggestions for addressing these challenges, including improving educational and PAG funding and increasing collaboration between PAGs and the medical community. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  17. CF Metadata Conventions: Founding Principles, Governance, and Future Directions

    NASA Astrophysics Data System (ADS)

    Taylor, K. E.

    2016-12-01

    The CF Metadata Conventions define attributes that promote sharing of climate and forecasting data and facilitate automated processing by computers. The development, maintenance, and evolution of the conventions have mainly been provided by voluntary community contributions. Nevertheless, an organizational framework has been established, which relies on established rules and web-based discussion to ensure smooth (but relatively efficient) evolution of the standard to accommodate new types of data. The CF standard has been essential to the success of high-profile internationally-coordinated modeling activities (e.g, the Coupled Model Intercomparison Project). A summary of CF's founding principles and the prospects for its future evolution will be discussed.

  18. Performance of cell-penetrating peptide-linked polymers physically mixed with poorly membrane-permeable molecules on cell membranes.

    PubMed

    Sakuma, Shinji; Suita, Masaya; Yamamoto, Takafumi; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Nakajima, Noriko; Shinkai, Norihiro; Yamauchi, Hitoshi; Hiwatari, Ken-Ichiro; Hashizume, Akio; Tachikawa, Hiroyuki; Kimura, Ryoji; Ishimaru, Yuki; Kasai, Atsushi; Maeda, Sadaaki

    2012-05-01

    We are investigating a new class of penetration enhancers that enable poorly membrane-permeable molecules physically mixed with them to effectively penetrate cell membranes without their concomitant cellular uptake. Since we previously revealed that poly(N-vinylacetamide-co-acrylic acid) modified with d-octaarginine, which is a typical cell-penetrating peptide, significantly enhanced the nasal absorption of insulin, we examined the performance of the polymers on cell membranes. When Caco-2 cells were incubated with 5(6)-carboxyfluorescein (CF) for 30 min, approximately 0.1% of applied CF was internalized into the cells. This poor membrane permeability was dramatically enhanced by d-octaarginine-linked polymers; a 25-fold increase in the cellular uptake of CF was observed when the polymer concentration was adjusted to 0.2mg/mL. None of the individual components, for example, d-octaarginine, had any influence on CF uptake, demonstrating that only d-octaarginine anchored chemically to the polymeric platform enhanced the membrane permeation of CF. The polymer-induced CF uptake was consistently high even when the incubation time was extended to 120 min. Confocal laser scanning microphotographs of cells incubated with d-octaarginine-linked polymers bearing rhodamine red demonstrated that the cell outline was stained with red fluorescence. The polymer-induced CF uptake was significantly suppressed by 5-(N-ethyl-N-isopropyl)amiloride, which is an inhibitor of macropinocytosis. Results indicated that d-octaarginine-linked polymers remained on the cell membrane and poorly membrane-permeable CF was continuously internalized into cells mainly via macropinocytosis repeated for the individual peptidyl branches in the polymer backbone. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. 24 CFR 905.400 - Capital Fund formula (CF formula).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... PHAs. (c) Allocation for existing modernization needs under the CF formula. HUD shall allocate one-half... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Capital Fund formula (CF formula... URBAN DEVELOPMENT THE PUBLIC HOUSING CAPITAL FUND PROGRAM Capital Fund Formula § 905.400 Capital Fund...

  20. Differentiation and Cell-Cell Interactions of Neural Progenitor Cells Transplanted into Intact Adult Brain.

    PubMed

    Sukhinich, K K; Kosykh, A V; Aleksandrova, M A

    2015-11-01

    We studied the behavior and cell-cell interactions of embryonic brain cell from GFP-reporter mice after their transplantation into the intact adult brain. Fragments or cell suspensions of fetal neocortical cells at different stages of development were transplanted into the neocortex and striatum of adult recipients. Even in intact brain, the processes of transplanted neurons formed extensive networks in the striatum and neocortical layers I and V-VI. Processes of transplanted cells at different stages of development attained the rostral areas of the frontal cortex and some of them reached the internal capsule. However, the cells transplanted in suspension had lower process growth potency than cells from tissue fragments. Tyrosine hydroxylase fibers penetrated from the recipient brain into grafts at both early and late stages of development. Our experiments demonstrated the formation of extensive reciprocal networks between the transplanted fetal neural cells and recipient brain neurons even in intact brain.

  1. 76 FR 27282 - Airworthiness Directives; General Electric Company CF34-10E2A1; CF34-10E5, CF34-10E5A1; CF34-10E6...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-11

    ... methods: Federal eRulemaking Portal: Go to http://www.regulations.gov . Follow the instructions for... Investigation of a General Electric Company (GE) CF34-10E turbofan engine experiencing high fan frame vibrations... likely to exist or develop in other products of the same type design. Proposed AD Requirements This...

  2. CFTR genotype and clinical outcomes of adult patients carried as cystic fibrosis disease.

    PubMed

    Bonadia, Luciana Cardoso; de Lima Marson, Fernando Augusto; Ribeiro, Jose Dirceu; Paschoal, Ilma Aparecida; Pereira, Monica Corso; Ribeiro, Antonio Fernando; Bertuzzo, Carmen Silvia

    2014-05-01

    There are nearly 2000 cystic fibrosis transmembrane regulator (CFTR) mutations that cause cystic fibrosis (CF). These mutations are classified into six classes; on the one hand, the first three classes cause severe disease involvement in early childhood, on the other hand, the Class IV, V and VI mutations cause minor severe disease in the same age. Nowadays, with therapeutic advances in CF management and competence of pediatricians, physicians of adults have to deal with two groups of CF patients: (i) adults diagnosed in childhood with severe mutations and (ii) adults who initiated symptoms in adulthood and with Class IV, V and VI mutations. The aim of this study was to analyze adults from a clinical center, treated as CF disease, screening the CFTR genotype and evaluating the clinical characteristics. Thirty patients followed as CF disease at the University Hospital were enrolled. After a complete molecular CFTR negative screening and sweat test levels between 40 and 59mEq/L, five patients were characterized as non-CF disease and were excluded. Molecular screening was performed by CFTR gene sequencing/MLPA or by specific mutation screening. Clinical data was obtained from medical records. The patients were divided into three groups: (1) patients with Class I, II and III mutations in two CFTR alleles; (2) genotype with at least one allele of Class IV, V or VI CFTR mutations and, (3) non-identified CFTR mutation+one patient with one allele with CFTR mutation screened (Class I). There was an association of CFTR class mutation and sodium/chloride concentration in the sweat test (sodium: p=0.040; chloride: p=0.016), onset of digestive symptoms (p=0.012), lung function parameter (SpO2 - p=0.016), Bhalla score (p=0.021), age at diagnosis (p=0.008) and CF-related diabetes (p=0.029). There was an association between Pseudomonas aeruginosa chronic colonization (as clinical marker for the lung disease status) and lung impairment (FEV1% - p=0.027; Bhalla score - p=0.021), CF

  3. Pressure and temperature induced elastic properties of Am and Cf monobismuthides

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

    Jain, S., E-mail: sanjay-rjain@rediffmail.com; Sushila Devi Bansal College of Engineering, Rau, Indore 452001; Shriya, S.

    2016-05-23

    The pressure and temperature dependent mechanical properties as melting temperature, hardness and brittle nature of XBi (X = Am and Cf) are studied. The rare earth actinides pnictides showed a structural phase transition (B1–B2) at a transition pressure (P{sub T}) of 14.3 GPa (AmBi) and 10.8 GPa (CfBi). Pressure dependence of melting temperature (T{sub m}) discerns an increase inferring the hardening or stiffening of the lattice as a consequence of bond compression and bond strengthening. Suppressed T{sub M} as functions of temperature infers the weakening of the lattice results in bond weakening in XBi (X = Am, Cf). Vickers Hardnessmore » (H{sub V}), Poisson’s and Pugh ratio of XBi (X = Am and Cf) demonstrates that XBi (X = Am and Cf) is mechanically stiffened, thermally softened and brittle on applied pressure and temperature.« less

  4. A pilot study on the use of cerebrospinal fluid cell-free DNA in intramedullary spinal ependymoma.

    PubMed

    Connolly, Ian David; Li, Yingmei; Pan, Wenying; Johnson, Eli; You, Linya; Vogel, Hannes; Ratliff, John; Hayden Gephart, Melanie

    2017-10-01

    Cerebrospinal fluid (CSF) represents a promising source of cell-free DNA (cfDNA) for tumors of the central nervous system. A CSF-based liquid biopsy may obviate the need for riskier tissue biopsies and serve as a means for monitoring tumor recurrence or response to therapy. Spinal ependymomas most commonly occur in adults, and aggressive resection must be delicately balanced with the risk of injury to adjacent normal tissue. In patients with subtotal resection, recurrence commonly occurs. A CSF-based liquid biopsy matched to the patient's spinal ependymoma mutation profile has potential to be more sensitive then surveillance MRI, but the utility has not been well characterized for tumors of the spinal cord. In this study, we collected matched blood, tumor, and CSF samples from three adult patients with WHO grade II intramedullary spinal ependymoma. We performed whole exome sequencing on matched tumor and normal DNA to design Droplet Digital™ PCR (ddPCR) probes for tumor and wild-type mutations. We then interrogated CSF samples for tumor-derived cfDNA by performing ddPCR on extracted cfDNA. Tumor cfDNA was not reliably detected in the CSF of our cohort. Anatomic sequestration and low grade of intramedullary spinal cord tumors likely limits the role of CSF liquid biopsy.

  5. A high level computational study of the CH4/CF4 dimer: how does it compare with the CH4/CH4 and CF4/CF4 dimers?

    NASA Astrophysics Data System (ADS)

    Biller, Matthew J.; Mecozzi, Sandro

    2012-04-01

    The interaction within the methane-methane (CH4/CH4), perfluoromethane-perfluoromethane (CF4/CF4) methane-perfluoromethane dimers (CH4/CF4) was calculated using the Hartree-Fock (HF) method, multiple orders of Møller-Plesset perturbation theory [MP2, MP3, MP4(DQ), MP4(SDQ), MP4(SDTQ)], and coupled cluster theory [CCSD, CCSD(T)], as well as the PW91, B97D, and M06-2X density functional theory (DFT) functionals. The basis sets of Dunning and coworkers (aug-cc-pVxZ, x = D, T, Q), Krishnan and coworkers [6-311++G(d,p), 6-311++G(2d,2p)], and Tsuzuki and coworkers [aug(df, pd)-6-311G(d,p)] were used. Basis set superposition error (BSSE) was corrected via the counterpoise method in all cases. Interaction energies obtained with the MP2 method do not fit with the experimental finding that the methane-perfluoromethane system phase separates at 94.5 K. It was not until the CCSD(T) method was considered that the interaction energy of the methane-perfluoromethane dimer (-0.69 kcal mol-1) was found to be intermediate between the methane (-0.51 kcal mol-1) and perfluoromethane (-0.78 kcal mol-1) dimers. This suggests that a perfluoromethane molecule interacts preferentially with another perfluoromethane (by about 0.09 kcal mol-1) than with a methane molecule. At temperatures much lower than the CH4/CF4 critical solution temperature of 94.5 K, this energy difference becomes significant and leads perfluoromethane molecules to associate with themselves, forming a phase separation. The DFT functionals yielded erratic results for the three dimers. Further development of DFT is needed in order to model dispersion interactions in hydrocarbon/perfluorocarbon systems.

  6. 21 CFR Appendixes C-F to Subpart B... - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false [Reserved] C Appendixes C-F to Subpart B of Part 26 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... COMMUNITY Specific Sector Provisions for Medical Devices Appendixes C-F to Subpart B of Part 26 [Reserved] ...

  7. 21 CFR Appendices C-F to Subpart B... - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false [Reserved] C Appendices C-F to Subpart B of Part 26 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... COMMUNITY Specific Sector Provisions for Medical Devices Appendices C-F to Subpart B of Part 26 [Reserved] ...

  8. A Pilot Study Exploring the Role of Physical Therapists and Transition in Care of Pediatric Patients with Cystic Fibrosis to the Adult Setting

    PubMed Central

    Packel, Lora; Sood, Megha; Gormley, Michelle; Hayden, Rebecca

    2013-01-01

    Background Cystic fibrosis (CF) is a disease that requires intensive multidisciplinary care, including care by physical therapists (PTs). People with CF are now living well into adulthood, necessitating a transfer of care from the pediatric setting to an adult one. Physical therapists play a large role in the care of the person with CF; however, there is little known about the PT role in transition of care. Purpose To explore transition issues for people with CF from the perspective of PTs. Methods An 18-question online survey was sent to PTs via an electronic CF listserv. Questions were derived from an analysis of transition literature in CF and other chronic childhood conditions. Physical therapists who reported treating people with CF gave their opinions on issues impacting transition from their perspective as well as their perception of patient and parent concerns. Descriptive statistics were used for data analysis. Results A total of 26 PTs completed the survey. A majority, 61.5%, reported that there was a transition program at their facility, with 42.3% involving physical therapy. Common themes for patients and parents included feeling uncertain about: knowledge of the adult physician, acquiring pulmonary infections in the adult setting, and pace of the adult clinic. Physical therapists were concerned about adherence with airway clearance and exercise following transfer to the adult clinic. Conclusions The role of PT in transition programs is quite varied. Physical therapists should address common concerns of their patients and families to improve the transition process and possibly impact adherence to the PT plan of care. PMID:23754936

  9. Complex toxin profile of French Mediterranean Ostreopsis cf. ovata strains, seafood accumulation and ovatoxins prepurification.

    PubMed

    Brissard, Charline; Herrenknecht, Christine; Séchet, Véronique; Hervé, Fabienne; Pisapia, Francesco; Harcouet, Jocelyn; Lémée, Rodolphe; Chomérat, Nicolas; Hess, Philipp; Amzil, Zouher

    2014-05-13

    Ostreopsis cf. ovata produces palytoxin analogues including ovatoxins (OVTXs) and a putative palytoxin (p-PLTX), which can accumulate in marine organisms and may possibly lead to food intoxication. However, purified ovatoxins are not widely available and their toxicities are still unknown. The aim of this study was to improve understanding of the ecophysiology of Ostreopsis cf. ovata and its toxin production as well as to optimize the purification process for ovatoxin. During Ostreopsis blooms in 2011 and 2012 in Villefranche-sur-Mer (France, NW Mediterranean Sea), microalgae epiphytic cells and marine organisms were collected and analyzed both by LC-MS/MS and hemolysis assay. Results obtained with these two methods were comparable, suggesting ovatoxins have hemolytic properties. An average of 223 μg·kg-1 of palytoxin equivalent of whole flesh was found, thus exceeding the threshold of 30 μg·kg-1 in shellfish recommended by the European Food Safety Authority (EFSA). Ostreopsis cells showed the same toxin profile both in situ and in laboratory culture, with ovatoxin-a (OVTX-a) being the most abundant analogue (~50%), followed by OVTX-b (~15%), p-PLTX (12%), OVTX-d (8%), OVTX-c (5%) and OVTX-e (4%). Ostreopsis cf. ovata produced up to 2 g of biomass per L of culture, with a maximum concentration of 300 pg PLTX equivalent cell-1. Thus, an approximate amount of 10 mg of PLTX-group toxins may be produced with 10 L of this strain. Toxin extracts obtained from collected biomass were purified using different techniques such as liquid-liquid partition or size exclusion. Among these methods, open-column chromatography with Sephadex LH20 phase yielded the best results with a cleanup efficiency of 93% and recovery of about 85%, representing an increase of toxin percentage by 13 fold. Hence, this purification step should be incorporated into future isolation exercises.

  10. Reactions in trifluoroacetic acid (CF 3COOH) induced by low energy electron attachment

    NASA Astrophysics Data System (ADS)

    Langer, Judith; Stano, Michal; Gohlke, Sascha; Foltin, Victor; Matejcik, Stefan; Illenberger, Eugen

    2006-02-01

    Dissociative electron attachment to trifluoroacetic acid (CF 3COOH) is characterized by an intense low energy shape resonance located near 1 eV and a comparatively weaker core excited resonance located near 7 eV. The shape resonance decomposes into the fragment ions CF 3COO -, CF 2COO -, and CF2-. The underlying reactions include simple bond cleavage but also more complex sequences involving multiple bond cleavages, rearrangement in the precursor ion and formation of new molecules (HF, CO 2). The core excited resonance additionally decomposes into F -, CF3- and probably metastable CO2-.

  11. Orchestrating brain-cell renewal: the role of immune cells in adult neurogenesis in health and disease.

    PubMed

    Ziv, Yaniv; Schwartz, Michal

    2008-11-01

    Immune cells and immune molecules have recently been shown to support neurogenesis from neural stem and progenitor cells in the adult brain. This non-classical immune activity takes place constantly under normal physiological conditions and is extended under acute pathological conditions to include the attraction of progenitor cells and induction of neurogenesis in regions of the adult central nervous system (CNS) in which formation of new neurons does not normally occur. We suggest that the immune system should be viewed as a novel player in the adult neural stem cell niche and a coordinator of cell renewal processes after injury. We discuss these notions in light of the well-known facts that both immune-cell activity and cell renewal are inherently limited in the adult CNS and that immune and stem cells provide the body's mechanisms of repair.

  12. Identification, Characterization, and Utilization of Adult Meniscal Progenitor Cells

    DTIC Science & Technology

    2015-09-01

    pluripotent stem cells for osteoarthritis drug screening . Arthritis Rheumatol. 66, 3062–3072. Xia, Y., Zheng, S., Bidthanapally, A., 2008. Depth-dependent...the development of knee osteoarthritis (OA). New treatments centered on the stem /progenitor cell population resident within the adult meniscus will be...biology to develop a profile of repair cells in the adult meniscus, track meniscal stem /progenitor cell (MSPC) behavior within meniscus as function of

  13. Pure rotation spectrum of CF4 in the v3 = 1 state using THz synchrotron radiation

    NASA Astrophysics Data System (ADS)

    Boudon, V.; Carlos, M.; Richard, C.; Pirali, O.

    2018-06-01

    Spherical-top tetrahedral species like CH4, SiH4, CF4, …possess no permanent dipole moment. Therefore, probing their pure rotation spectrum is very challenging since only a very weak dipole moment can be induced by centrifugal distortion and/or rovibrational interaction. If some Q branch lines have been recorded thanks to microwave techniques, R branch lines in the THz region have been poorly explored until recently. In previous studies, we have reported the pure rotation THz spectrum of cold and hot band lines of methane recorded at the SOLEIL Synchrotron facility. Here, we present the first recorded THz spectrum of the R branch of CF4, a powerful greenhouse gas, in its v3 = 1 state. This Fourier transform spectrum covers the R (20) to R (37) line clusters, in the 20-37 cm-1 spectral range. It was recorded thanks to a 150 m multiple path cell at room temperature. We could estimate the vibration-induced dipole moment value and also include the recorded line positions in a global fit of many CF4 transitions.

  14. Validation of the Rossmax CF175 upper-arm blood pressure monitor for home blood pressure monitoring according to the European Society of Hypertension International Protocol revision 2010.

    PubMed

    Zhang, Lu; Kang, Yuan-Yuan; Zeng, Wei-Fang; Li, Yan; Wang, Ji-Guang

    2015-04-01

    The present study aimed to evaluate the accuracy of the Rossmax CF175 upper-arm blood pressure monitor for home blood pressure monitoring according to the International Protocol of the European Society of Hypertension revision 2010. Systolic and diastolic blood pressures were sequentially measured in 33 adult Chinese (17 women, mean age 46 years) using a mercury sphygmomanometer (two observers) and the Rossmax CF175 device (one supervisor). A total of 99 pairs of comparisons were obtained from 33 participants for judgments in two parts with three grading phases. All the blood pressure requirements were fulfilled. The Rossmax CF175 device achieved the targets in part 1 of the validation study. The number of absolute differences between the device and observers within 5, 10, and 15 mmHg was 78/99, 94/99, and 98/99, respectively, for systolic blood pressure, and 81/99, 96/99, and 97/99, respectively, for diastolic blood pressure. The device also achieved the criteria in part 2 of the validation study. Twenty-nine participants, for both of systolic and diastolic blood pressure, had at least two of the three device-observers differences within 5 mmHg (required ≥24). Only one participant for diastolic blood pressure had all three device-observers comparisons greater than 5 mmHg. The Rossmax automated oscillometric upper-arm blood pressure monitor CF175 fulfilled the requirements of the International Protocol revision 2010, and hence can be recommended for blood pressure measurement in adults.

  15. Signaling mechanisms regulating adult neural stem cells and neurogenesis

    PubMed Central

    Faigle, Roland; Song, Hongjun

    2012-01-01

    Background Adult neurogenesis occurs throughout life in discrete regions of the mammalian brain and is tightly regulated via both extrinsic environmental influences and intrinsic genetic factors. In recent years, several crucial signaling pathways have been identified in regulating self-renewal, proliferation, and differentiation of neural stem cells, as well as migration and functional integration of developing neurons in the adult brain. Scope of review Here we review our current understanding of signaling mechanisms, including Wnt, notch, sonic hedgehog, growth and neurotrophic factors, bone morphogenetic proteins, neurotransmitters, transcription factors, and epigenetic modulators, and crosstalk between these signaling pathways in the regulation of adult neurogenesis. We also highlight emerging principles in the vastly growing field of adult neural stem cell biology and neural plasticity. Major conclusions Recent methodological advances have enabled the field to identify signaling mechanisms that fine-tune and coordinate neurogenesis in the adult brain, leading to a better characterization of both cell-intrinsic and environmental cues defining the neurogenic niche. Significant questions related to niche cell identity and underlying regulatory mechanisms remain to be fully addressed and will be the focus of future studies. General significance A full understanding of the role and function of individual signaling pathways in regulating neural stem cells and generation and integration of newborn neurons in the adult brain may lead to targeted new therapies for neurological diseases in humans. PMID:22982587

  16. Expansion of Multipotent Stem Cells from the Adult Human Brain

    PubMed Central

    Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

    2013-01-01

    The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

  17. Cystic fibrosis epithelial cells are primed for apoptosis as a result of increased Fas (CD95).

    PubMed

    Chen, Qiwei; Pandi, Sudha Priya Soundara; Kerrigan, Lauren; McElvaney, Noel G; Greene, Catherine M; Elborn, J Stuart; Taggart, Clifford C; Weldon, Sinéad

    2018-02-24

    Previous work suggests that apoptosis is dysfunctional in cystic fibrosis (CF) airways with conflicting results. We evaluated the relationship between dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) and apoptosis in CF airway epithelial cells. Apoptosis and associated caspase activity were analysed in non-CF and CF tracheal and bronchial epithelial cell lines. Basal levels of apoptosis and activity of caspase-3 and caspase-8 were significantly increased in CF epithelial cells compared to controls, suggesting involvement of extrinsic apoptosis signalling, which is mediated by the activation of death receptors, such as Fas (CD95). Increased levels of Fas were observed in CF epithelial cells and bronchial brushings from CF patients compared to non-CF controls. Neutralisation of Fas significantly inhibited caspase-3 activity in CF epithelial cells compared to untreated cells. In addition, activation of Fas significantly increased caspase-3 activity and apoptosis in CF epithelial cells compared to control cells. Overall, these results suggest that CF airway epithelial cells are more sensitive to apoptosis via increased levels of Fas and subsequent activation of the Fas death receptor pathway, which may be associated with dysfunctional CFTR. Copyright © 2018 European Cystic Fibrosis Society. All rights reserved.

  18. Toward understanding family-related characteristics of young adults with sickle-cell disease or sickle-cell trait in the USA.

    PubMed

    Hershberger, Patricia E; Gallo, Agatha M; Molokie, Robert; Thompson, Alexis A; Suarez, Marie L; Yao, Yingwei; Dallas, Constance M; Wilkie, Diana J

    2016-06-01

    To describe the family-related characteristics of young adults with sickle-cell disease or sickle-cell trait prior to taking part in a randomised controlled trial on sickle-cell reproductive health education. There is a critical need for educational programmes that target the reproductive needs of young adults with sickle-cell disease or trait. However, little is known about the family-related characteristics (i.e., demographic attributes and reproductive health behaviours) in which these young adults live. A descriptive cross-sectional analysis. At study enrolment, 234 young adults (mean age = 25·9 years, 65% female) completed the SCKnowIQ questionnaire. Descriptive statistics depict the demographic attributes and reproductive health behaviours of young adults with sickle-cell disease (n = 138) or trait (n = 96). For group comparisons, independent t tests or Fisher's tests were used, as appropriate. Young adults with sickle-cell trait had significantly higher education, income and health insurance than those with sickle-cell disease. Both groups believed that sickle-cell disease was a severe condition. A majority of young adults with sickle-cell disease (65%) had no children compared to 42% of those with sickle-cell trait. Most young adults (85% sickle-cell disease, 82% sickle-cell trait) were not planning a pregnancy in the next six months, and many used condoms, withdrawal or oral contraceptives. Socioeconomic disparities exist between young adults with sickle-cell disease and sickle-cell trait. Future research that advances education about how and when to communicate appropriate genetic risk information to partners and children especially for young adults with sickle-cell trait would be beneficial. Awareness of the similarities and differences in the family-related characteristics among young adults with sickle-cell disease or trait can allow for more tailored reproductive education. © 2016 John Wiley & Sons Ltd.

  19. Toward Understanding Family-Related Characteristics of Young Adults with Sickle Cell Disease or Sickle Cell Trait in the USA

    PubMed Central

    Hershberger, Patricia E.; Gallo, Agatha M.; Molokie, Robert; Thompson, Alexis A.; Suarez, Marie L.; Yao, Yingwei; Dallas, Constance M.; Wilkie, Diana J.

    2016-01-01

    Aims and objectives To describe the family-related characteristics of young adults with sickle cell disease or sickle cell trait prior to taking part in a randomized controlled trial on sickle cell reproductive health education. Background There is a critical need for educational programs that target the reproductive needs of young adults with sickle cell disease or trait. However, little is known about the family-related characteristics (i.e., demographic attributes and reproductive health behaviors) in which these young adults live. Design A descriptive cross-sectional analysis. Method At study enrollment, 234 young adults (mean age = 25.9 years, 65% female) completed the SCKnowIQ questionnaire. Descriptive statistics depict the demographic attributes and reproductive health behaviors of young adults with sickle cell disease (n = 138) or trait (n = 96). For group comparisons, independent t tests or Fisher’s tests were used, as appropriate. Results Young adults with sickle cell trait had significantly higher education, income, and health insurance than those with sickle cell disease. Both groups believed that sickle cell disease was a severe condition. A majority of young adults with sickle cell disease (65%) had no children compared to 42% of those with sickle cell trait. Most young adults (85% sickle cell disease, 82% sickle cell trait) were not planning a pregnancy in the next six months and many used condoms, withdrawal, or oral contraceptives. Conclusions Socioeconomic disparities exist between young adults with sickle cell disease and sickle cell trait. Future research that advances education about how and when to communicate appropriate genetic risk information to partners and children especially for young adults with sickle cell trait would be beneficial. Relevance to clinical practice Awareness of the similarities and differences in the family-related characteristics among young adults with sickle cell disease or trait can allow for more tailored

  20. Stromal p16 Overexpression in Adult Granulosa Cell Tumors of the Ovary.

    PubMed

    Na, Kiyong; Sung, Ji-Youn; Kim, Hyun-Soo

    2017-05-01

    Adult granulosa cell tumor of the ovary is usually diagnosed at an early stage. However, most patients with advanced or recurrent disease will die of the disease due to limited treatment options. Data on the stromal p16 expression of ovarian adult granulosa cell tumors are limited. The aim of this study was to analyze the immunohistochemical p16 expression in the peritumoral stroma of primary and recurrent adult granulosa cell tumors and investigate whether there were significant differences in stromal p16 expression among nonpathological ovaries, benign sex cord-stromal tumors, and adult granulosa cell tumors. This study included 13 and 11 cases of primary and recurrent adult granulosa cell tumors, respectively. Non-pathological ovaries and benign sex cord-stromal tumors showed negative or weak positive expression, whereas most of the adult granulosa cell tumors showed diffuse and moderate-to-strong immunostaining. Primary adult granulosa cell tumors had significantly higher stromal p16 expression levels than nonpathological ovaries and benign sex cord-stromal tumors (p<0.001). Moreover, recurrent adult granulosa cell tumors showed significantly elevated levels of stromal p16 expression compared to primary adult granulosa cell tumors (p=0.032). In contrast, the difference in stromal p16 expression between non-pathological ovaries and benign sex cord-stromal tumors was not statistically significant (p=0.522). Our observations suggest that stromal p16 expression may be involved in the development and progression of ovarian adult granulosa cell tumors. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Pharmacokinetics and Tolerability of Oral Sildenafil in Adults with Cystic Fibrosis Lung Disease

    PubMed Central

    Taylor-Cousar, JL; Wiley, C; Felton, LA; St Clair, C; Jones, M; Curran-Everett, D; Poch, K; Nichols, DP; Solomon, GM; Saavedra, MT; Accurso, FJ; Nick, JA

    2014-01-01

    Rationale Airway inflammation is central to cystic fibrosis (CF) pathophysiology. Pre-clinical models have shown that phosphodiesterase inhibitors (PDEi) like sildenafil have anti-inflammatory activity. PDEi have not been studied in CF subjects. Objectives We evaluated the pharmacokinetics, tolerability, and safety of sildenafil in subjects with CF. Sputum biomarkers were used to explore efficacy. Methods An open-label pilot study of oral sildenafil administration was conducted in adults with mild to moderate CF lung disease. Subjects received oral sildenafil 20 or 40 mg p.o. t.i.d. for 6 weeks. Measurements and Main Results Twenty subjects completed the study. Estimated elimination rate constants were statistically different in subjects with CF compared to previously published non-CF subjects. Side effects were generally mild. There were no drug-related serious adverse events. Sputum neutrophil elastase activity decreased. Conclusions Subjects with CF may eliminate sildenafil at a faster rate than non-CF subjects. Sildenafil administration was safe in subjects with CF, and decreased sputum elastase activity. Sildenafil warrants further study as an anti-inflammatory in CF. PMID:25466700

  2. Development of a Method to Implement Whole-Genome Bisulfite Sequencing of cfDNA from Cancer Patients and a Mouse Tumor Model.

    PubMed

    Maggi, Elaine C; Gravina, Silvia; Cheng, Haiying; Piperdi, Bilal; Yuan, Ziqiang; Dong, Xiao; Libutti, Steven K; Vijg, Jan; Montagna, Cristina

    2018-01-01

    The goal of this study was to develop a method for whole genome cell-free DNA (cfDNA) methylation analysis in humans and mice with the ultimate goal to facilitate the identification of tumor derived DNA methylation changes in the blood. Plasma or serum from patients with pancreatic neuroendocrine tumors or lung cancer, and plasma from a murine model of pancreatic adenocarcinoma was used to develop a protocol for cfDNA isolation, library preparation and whole-genome bisulfite sequencing of ultra low quantities of cfDNA, including tumor-specific DNA. The protocol developed produced high quality libraries consistently generating a conversion rate >98% that will be applicable for the analysis of human and mouse plasma or serum to detect tumor-derived changes in DNA methylation.

  3. The application of PA/CF in stab resistance body armor

    NASA Astrophysics Data System (ADS)

    Yuan, M. Q.; Liu, Y.; Gong, Z.; Qian, X. M.

    2017-06-01

    Stab resistance body armor (SRBA) is an essential defensive equipment to protect human body against injuries from stabbing. The conventional SRBAs shared low wearing frequency since they are heavy and poor in flexibility. This paper designed a structured stab-resistance plate using the model of crocodile armor and manufactured using 3D printing technology-laser sintering (LS). CF(Carbon fiber) was applied to enhance the stab resistance properties of SRBA. The effects of the material and structure were analysed through the stab resistance property tests based on the national standard GA68-2008. It is found that the stab resistance property of flat plates sintered by PA powder and PA/CF are both weaker than that of the structured plate. The penetrating depth of PA/CF structured plate is significantly 2-mm-less than the pure PA structured plate. The SEM observations confirmed the conclusion that addition of the CF largely improved the plate stab resistance property. Moreover, using PA/CF structured plate to produce the stab resistance body armor would result in a weight reduction by about 30-40% as compared to the existing SRBA that was made up of metal plates, which could largely reduce the wearer physical burden and improve the wearing frequency.

  4. Cell-free chromatin from dying cancer cells integrate into genomes of bystander healthy cells to induce DNA damage and inflammation

    PubMed Central

    Mittra, Indraneel; Samant, Urmila; Sharma, Suvarna; Raghuram, Gorantla V; Saha, Tannistha; Tidke, Pritishkumar; Pancholi, Namrata; Gupta, Deepika; Prasannan, Preeti; Gaikwad, Ashwini; Gardi, Nilesh; Chaubal, Rohan; Upadhyay, Pawan; Pal, Kavita; Rane, Bhagyeshri; Shaikh, Alfina; Salunkhe, Sameer; Dutt, Shilpee; Mishra, Pradyumna K; Khare, Naveen K; Nair, Naveen K; Dutt, Amit

    2017-01-01

    Bystander cells of the tumor microenvironment show evidence of DNA damage and inflammation that can lead to their oncogenic transformation. Mediator(s) of cell–cell communication that brings about these pro-oncogenic pathologies has not been identified. We show here that cell-free chromatin (cfCh) released from dying cancer cells are the key mediators that trigger both DNA damage and inflammation in the surrounding healthy cells. When dying human cancer cells were cultured along with NIH3T3 mouse fibroblast cells, numerous cfCh emerged from them and rapidly entered into nuclei of bystander NIH3T3 cells to integrate into their genomes. This led to activation of H2AX and inflammatory cytokines NFκB, IL-6, TNFα and IFNγ. Genomic integration of cfCh triggered global deregulation of transcription and upregulation of pathways related to phagocytosis, DNA damage and inflammation. None of these activities were observed when living cancer cells were co-cultivated with NIH3T3 cells. However, upon intravenous injection into mice, both dead and live cells were found to be active. Living cancer cells are known to undergo extensive cell death when injected intravenously, and we observed that cfCh emerging from both types of cells integrated into genomes of cells of distant organs and induced DNA damage and inflammation. γH2AX and NFκB were frequently co-expressed in the same cells suggesting that DNA damage and inflammation are closely linked pathologies. As concurrent DNA damage and inflammation is a potent stimulus for oncogenic transformation, our results suggest that cfCh from dying cancer cells can transform cells of the microenvironment both locally and in distant organs providing a novel mechanism of tumor invasion and metastasis. The afore-described pro-oncogenic pathologies could be abrogated by concurrent treatment with chromatin neutralizing/degrading agents suggesting therapeutic possibilities. PMID:28580170

  5. [Transition - how adolescents with cystic fibrosis their parents experience the change from paediatric to adult care].

    PubMed

    Becher, Christine; Regamey, Nicolas; Spichiger, Elisabeth

    2014-12-01

    Cystic Fibrosis is the most common autosomal-recessive hereditary disease among white Europeans. The average survival of CF patients has increased to above 40 years and transition from paediatric to adult care has therefore become a significant issue. With this study, experiences of adolescents with CF and their parents with the transition from the paediatric to the adult care were explored. At a Swiss university CF centre, six adolescents and their mothers were recruited. Twelve narrative interviews were conducted on how the phase of transition was experienced. The transcribed interviews were analysed according to the method of hermeneutic phenomenology. Positive and negative experiences with long term routine care in the paediatric service, general themes of adolescence and the quality of the relationship with paediatric doctors influenced the families' experience during transition significantly. For mothers, insensitive information on the CF diagnosis might have influenced the transition experience. The adolescents welcomed an individualized and age appropriate care. Continuity in care, the announcement of, and involvement in the planning of the transfer were of great importance. The families particularly appreciated the timed adaptations of the transfer to individual needs. Flexibility and a strong collaboration between paediatric and adult CF teams are most relevant in the care of families.

  6. Stimulated Raman spectroscopy of 13CF4

    NASA Astrophysics Data System (ADS)

    Martínez, R. Z.; Bermejo, D.; Boudon, V.

    2018-06-01

    CF4 is a powerful greenhouse gas, mostly released in the atmosphere by industries. A careful modeling of its absorption spectrum is required in order to allow accurate atmospheric concentration measurements. For this aim, high resolution Raman spectroscopy is of great help, since it gives access to rovibrational levels that are not directly reachable through dipolar absorption, although they are involved in hot band generation. Following our previous work on 12CF4, we present here a similar investigation of the second isotopologue, 13CF4. The spectra of the ν1 (909.21 cm-1), 2ν1 -ν1 (906.77 cm-1), ν1 +ν2 -ν2 (909.33 cm-1), ν2 (435.47 cm-1), 2ν2 (868.10 cm-1) and 3ν2 -ν2 (865.73 cm-1) bands were obtained with a quasi-continuous wave stimulated Raman spectrometer. These six bands were studied at temperatures of 140 and 298 K (for the hot bands). These spectra could be assigned and modeled thanks to the XTDS and SPVIEW software developed in the Dijon group.

  7. Contaminant concentration in environmental samples using LIBS and CF-LIBS

    NASA Astrophysics Data System (ADS)

    Pandhija, S.; Rai, N. K.; Rai, A. K.; Thakur, S. N.

    2010-01-01

    The present paper deals with the detection and quantification of toxic heavy metals like Cd, Co, Pb, Zn, Cr, etc. in environmental samples by using the technique of laser-induced breakdown spectroscopy (LIBS) and calibration-free LIBS (CF-LIBS). A MATLABTM program has been developed based on the CF-LIBS algorithm given by earlier workers and concentrations of pollutants present in industrial area soil have been determined. LIBS spectra of a number of certified reference soil samples with varying concentrations of toxic elements (Cd, Zn) have been recorded to obtain calibration curves. The concentrations of Cd and Zn in soil samples from the Jajmau area, Kanpur (India) have been determined by using these calibration curves and also by the CF-LIBS approach. Our results clearly demonstrate that the combination of LIBS and CF-LIBS is very useful for the study of pollutants in the environment. Some of the results have also been found to be in good agreement with those of ICP-OES.

  8. Quiescent gastric stem cells maintain the adult Drosophila stomach.

    PubMed

    Strand, Marie; Micchelli, Craig A

    2011-10-25

    The adult Drosophila copper cell region or "stomach" is a highly acidic compartment of the midgut with pH < 3. In this region, a specialized group of acid-secreting cells similar to mammalian gastric parietal cells has been identified by a unique ultrastructure and by copper-metallothionein fluorescence. However, the homeostatic mechanism maintaining the acid-secreting "copper cells" of the adult midgut has not been examined. Here, we combine cell lineage tracing and genetic analysis to investigate the mechanism by which the gastric epithelium is maintained. Our investigation shows that a molecularly identifiable population of multipotent, self-renewing gastric stem cells (GSSCs) produces the acid-secreting copper cells, interstitial cells, and enteroendocrine cells of the stomach. Our assays demonstrate that GSSCs are largely quiescent but can be induced to regenerate the gastric epithelium in response to environmental challenge. Finally, genetic analysis reveals that adult GSSC maintenance depends on Wnt signaling. Characterization of the GSSC lineage in Drosophila, with striking similarities to mammals, will advance the study of both homeostatic and pathogenic processes in the stomach.

  9. Pluripotency of adult stem cells derived from human and rat pancreas

    NASA Astrophysics Data System (ADS)

    Kruse, C.; Birth, M.; Rohwedel, J.; Assmuth, K.; Goepel, A.; Wedel, T.

    Adult stem cells are undifferentiated cells found within fully developed tissues or organs of an adult individuum. Until recently, these cells have been considered to bear less self-renewal ability and differentiation potency compared to embryonic stem cells. In recent studies an undifferentiated cell type was found in primary cultures of isolated acini from exocrine pancreas termed pancreatic stellate cells. Here we show that pancreatic stellate-like cells have the capacity of extended self-renewal and are able to differentiate spontaneously into cell types of all three germ layers expressing markers for smooth muscle cells, neurons, glial cells, epithelial cells, chondrocytes and secretory cells (insulin, amylase). Differentiation and subsequent formation of three-dimensional cellular aggregates (organoid bodies) were induced by merely culturing pancreatic stellate-like cells in hanging drops. These cells were developed into stable, long-term, in vitro cultures of both primary undifferentiated cell lines as well as organoid cultures. Thus, evidence is given that cell lineages of endodermal, mesodermal, and ectodermal origin arise spontaneously from a single adult undifferentiated cell type. Based on the present findings it is assumed that pancreatic stellate-like cells are a new class of lineage uncommitted pluripotent adult stem cells with a remarkable self-renewal ability and differentiation potency. The data emphasize the versatility of adult stem cells and may lead to a reappraisal of their use for the treatment of inherited disorders or acquired degenerative diseases.

  10. The AREST CF experience in biobanking - More than just tissues, tubes and time.

    PubMed

    Garratt, Luke W; Kicic, Anthony; Robertson, Colin; Ranganathan, Sarath; Sly, Peter D; Stick, Stephen M

    2017-09-01

    Research to further improve outcomes for people with CF is dependent upon well characterised, archived and accessible clinical specimens. The recent article by Beekman et al. published in Journal of Cystic Fibrosis summarised a scientific meeting at the 13th ECFS Basic Science Conference. This meeting discussed how well-annotated, clinical biobanks for CF could be established in Europe to meet the needs of therapeutic development. The Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) has conducted biobanking of CF research and clinical specimens since the late 1990s and is custodian of the most comprehensive paediatric CF biobank in the world that focuses on the first years of life. This short communication will describe the approach undertaken by AREST CF in establishing a clinical specimen biobank. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  11. Cell phone use by adults with intellectual disabilities.

    PubMed

    Bryen, Diane Nelson; Carey, Allison; Friedman, Mark

    2007-02-01

    Although cell phone use has grown dramatically, there is a gap in cell phone access between people with disabilities and the general public. The importance of cell phone use among people with intellectual disabilities and studies about use of cell phones by adults with intellectual disabilities was described. Our goal was to determine the extent and scope of cell phone use by 83 adults with intellectual disabilities, reasons for nonuse, and factors affecting use. Results suggest a gap in the use of cell phone technology between people with intellectual disabilities and the general population. When used, they are employed primarily for emergencies, storing telephone numbers, and day-to-day communication. Chief reasons for nonuse include cost, perception of not needing one, and lack of accessibility.

  12. [Adult T-cell leukemia/lymphoma associated with unusual positivity of anti-ATLA (adult T-cell leukemia-cell-associated antigen) antibodies].

    PubMed

    Eto, T; Okamura, H; Okamura, T; Gondo, H; Kudo, J; Shibuya, T; Harada, M; Niho, Y

    1990-03-01

    A 56-year-old female was admitted because of generalized lymphadenopathy. Based upon histological findings of biopsied lymph node, malignant lymphoma, diffuse large cell type was diagnosed. The surface marker analysis showed that malignant cells were positive for CD4 and CD2 but negative for CD8. Although anti-ATLA (adult T-cell leukemia associated antigen) antibody was negative with the use of a gelatin particle agglutination method (P.A.), other methods such as an indirect immunofluorescence assay (I.F.), an enzyme-linked immunosorbent assay (E.I.A.) and a Western blotting assay revealed the positivity for anti-ATLA antibody. Adult T-cell leukemia/lymphoma (ATL/L) was confirmed by the presence of monoclonal integration of HTLV-I proviral DNA in biopsied specimen. This case, showing a pattern of P.A. (-) and I.F. (+), is extremely unusual, because I.F. and P.A. show highly close correlation. Thus, it is important to employ different methods for screening of anti-ATLA antibodies in the diagnosis of ATL/L.

  13. In situ X-ray diffraction analysis of (CF x) n batteries: signal extraction by multivariate analysis

    DOE PAGES

    Rodriguez, Mark A.; Keenan, Michael R.; Nagasubramanian, Ganesan

    2007-11-10

    In this study, (CF x) n cathode reaction during discharge has been investigated using in situ X-ray diffraction (XRD). Mathematical treatment of the in situ XRD data set was performed using multivariate curve resolution with alternating least squares (MCR–ALS), a technique of multivariate analysis. MCR–ALS analysis successfully separated the relatively weak XRD signal intensity due to the chemical reaction from the other inert cell component signals. The resulting dynamic reaction component revealed the loss of (CF x) n cathode signal together with the simultaneous appearance of LiF by-product intensity. Careful examination of the XRD data set revealed an additional dynamicmore » component which may be associated with the formation of an intermediate compound during the discharge process.« less

  14. [Langerhans cell histiocytosis in adults].

    PubMed

    Néel, A; Artifoni, M; Donadieu, J; Lorillon, G; Hamidou, M; Tazi, A

    2015-10-01

    Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells, most often organized in granulomas. The disease has been initially described in children. The clinical picture of LCH is highly variable. Bone, skin, pituitary gland, lung, central nervous system, lymphoid organs are the main organs involved whereas liver and intestinal tract localizations are less frequently encountered. LCH course ranges from a fulminant multisystem disease to spontaneous resolution. Several randomized controlled trials have enable pediatricians to refine the management of children with LCH. Adult LCH has some specific features and poses distinct therapeutic challenges, knowing that data on these patients are limited. Herein, we will provide an overview of current knowledge regarding adult LCH and its management. We will also discuss recent advances in the understanding of the disease, (i.e. the role of BRAF oncogene) that opens the way toward targeted therapies. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  15. Transition Metal-Mediated and -Catalyzed C-F Bond Activation via Fluorine Elimination.

    PubMed

    Fujita, Takeshi; Fuchibe, Kohei; Ichikawa, Junji

    2018-06-28

    Activation of carbon-fluorine (C-F) bonds is an important topic in synthetic organic chemistry recently. Among the methods for C-F bond cleavage, metal mediated and catalyzed β- or α-fluorine elimination proceeds under mild conditions compared with oxidative addition of C-F bond. The β- or α-fluorine elimination is initiated from organometallic intermediates having fluorine substituents on carbon atoms β or α to metal centers, respectively. Transformations via these elimination processes (C-F bond cleavage), which are typically preceded by carbon-carbon (or carbon-heteroatom) bond formation, have been remarkably developed as C-F bond activation methods in the past five years. In this minireview, we summarize the applications of transition metal-mediated and -catalyzed fluorine elimination to synthetic organic chemistry from a historical perspective for early studies and from a systematic perspective for recent studies. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Prevalence of dyslipidemia in adults with cystic fibrosis.

    PubMed

    Rhodes, Bronwen; Nash, Edward F; Tullis, Elizabeth; Pencharz, Paul B; Brotherwood, Michelle; Dupuis, Annie; Stephenson, Anne

    2010-01-01

    A high fat calorie diet is advocated for patients with cystic fibrosis (CF) however the lipid profiles of individuals with CF, including those with CF-related diabetes (CFRD), are not well studied. We conducted a retrospective review of adult CF patients attending St Michael's Hospital between January 2005 and December 2007. 334 patients (77% pancreatic insufficient (PI)) were included in the study. Mean HDL cholesterol was significantly lower in males (p<0.0001) with 44% of males having HDL cholesterol <38.7mg/dL(1mmol/L). Pancreatic sufficient patients were more likely than PI subjects to have total cholesterol >201mg/dL(5.2mmol/L) (p<0.01). 5% of subjects had triglyceride concentrations >195mg/dL(2.2mmol/L). Diabetes was diagnosed in 23% of subjects. Lipid profiles were similar between diabetics and non-diabetics. Total cholesterol and triglycerides both increased with increasing age and increasing BMI (p<0.01). Dyslipidemia occurs in CF patients however no differences in lipid profiles were seen between those with diabetes and those without. Fasting lipids should be monitored in CF patients, particularly those with PS, older age, and high BMI. As survival in CF increases, the prevalence of dyslipidemia may increase resulting in clinically important complications.

  17. Adult Mouse Cortical Cell Taxonomy by Single Cell Transcriptomics

    PubMed Central

    Tasic, Bosiljka; Menon, Vilas; Nguyen, Thuc Nghi; Kim, Tae Kyung; Jarsky, Tim; Yao, Zizhen; Levi, Boaz; Gray, Lucas T.; Sorensen, Staci A.; Dolbeare, Tim; Bertagnolli, Darren; Goldy, Jeff; Shapovalova, Nadiya; Parry, Sheana; Lee, Changkyu; Smith, Kimberly; Bernard, Amy; Madisen, Linda; Sunkin, Susan M.; Hawrylycz, Michael; Koch, Christof; Zeng, Hongkui

    2016-01-01

    Nervous systems are composed of various cell types, but the extent of cell type diversity is poorly understood. Here, we construct a cellular taxonomy of one cortical region, primary visual cortex, in adult mice based on single cell RNA-sequencing. We identify 49 transcriptomic cell types including 23 GABAergic, 19 glutamatergic and seven non-neuronal types. We also analyze cell-type specific mRNA processing and characterize genetic access to these transcriptomic types by many transgenic Cre lines. Finally, we show that some of our transcriptomic cell types display specific and differential electrophysiological and axon projection properties, thereby confirming that the single cell transcriptomic signatures can be associated with specific cellular properties. PMID:26727548

  18. Genetic alteration and mutation profiling of circulating cell-free tumor DNA (cfDNA) for diagnosis and targeted therapy of gastrointestinal stromal tumors.

    PubMed

    Yan, Weixin; Zhang, Aiguo; Powell, Michael J

    2016-07-21

    Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive type of tumor, different from smooth muscle and neural tumors of the gastrointestinal tract. The identification of genetic aberrations in proto-oncogenes that drive the growth of GISTs is critical for improving the efficacy of cancer therapy by matching targeted drugs to specific mutations. Research into the oncogenic mechanisms of GISTs has found that these tumors frequently contain activating gene mutations in either platelet-derived growth factor receptor A (PDGFRA) or a receptor tyrosine protein associated with a mast cell growth factor receptor encoded by the KIT gene. Mutant cancer subpopulations have the potential to disrupt durable patient responses to molecularly targeted therapy for GISTs, yet the prevalence and size of subpopulations remain largely unexplored. Detection of the cancer subpopulations that harbor low-frequency mutant alleles of target proto-oncogenes through the use of molecular genetic methods, such as polymerase chain reaction (PCR) target amplification technology, is hampered by the high abundance of wild-type alleles, which limit the sensitivity of detection of these minor mutant alleles. This is especially true in the case of mutant tumor DNA derived "driver" and "drug-resistant" alleles that are present in the circulating cell-free tumor DNA (cfDNA) in the peripheral blood circulation of GIST patients. So-called "liquid biopsy" allows for the dynamic monitoring of the patients' tumor status during treatment using minimally invasive sampling. New methodologies, such as a technology that employs a xenonucleic acid (XNA) clamping probe to block the PCR amplification of wild-type templates, have allowed improved molecular detection of these low-frequency alleles both in tissue biopsy samples and in cfDNA. These new methodologies could be widely applied for minimally invasive molecular testing in the therapeutic management of GISTs.

  19. 76 FR 68634 - Airworthiness Directives; General Electric Company (GE) CF6 Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-07

    ... Airworthiness Directives; General Electric Company (GE) CF6 Turbofan Engines AGENCY: Federal Aviation... ``(c) This AD applies to * * * and CF6-80A3 turbofan engines with left-hand links * * *.'' to ``(c) This AD applies to * * * and CF6-80A3 turbofan engines, including engines marked on the engine data...

  20. Predictors and variation of routine home discharge in critically ill adults with cystic fibrosis.

    PubMed

    Oud, Lavi; Chan, Yiu Ming

    2018-06-01

    The short-term outcomes of patients with cystic fibrosis (CF) surviving critical illness were not examined systematically. To determine the factors associated with and variation in rates of routine home discharge among ICU-managed adult CF patients. Predictors of routine home discharge and its hospital-level variation were examined in ICU-managed adults with cystic fibrosis in Texas during 2004-2013. Older age, rural residence, and severity of illness decreased odds of routine home discharge, while hospitalization in facilities accredited as part of the Cystic Fibrosis Foundation Care Center Network nearly doubled the odds of routine home discharge. The median (interquartile) adjusted rate of routine home discharge was 62.0% (31.5-82.5). The identified determinants of routine home discharge can inform clinical decision-making, while the demonstrated wide variation in adjusted across-hospital rates of routine home discharge of ICU-managed adults with CF can provide benchmark data for future quality improvement efforts. Published by Elsevier Inc.

  1. A Cell Model to Evaluate Chemical Effects on Adult Human Cardiac Progenitor Cell Differentiation and Function

    EPA Science Inventory

    Adult cardiac stem cells (CSC) and progenitor cells (CPC) represent a population of cells in the heart critical for its regeneration and function over a lifetime. The impact of chemicals on adult human CSC/CPC differentiation and function is unknown. Research was conducted to dev...

  2. OligoG CF-5/20 normalizes cystic fibrosis mucus by chelating calcium.

    PubMed

    Ermund, Anna; Recktenwald, Christian V; Skjåk-Braek, Gudmund; Meiss, Lauren N; Onsøyen, Edvar; Rye, Philip D; Dessen, Arne; Myrset, Astrid Hilde; Hansson, Gunnar C

    2017-06-01

    The goal of this study was to determine whether the guluronate (G) rich alginate OligoG CF-5/20 (OligoG) could detach cystic fibrosis (CF) mucus by calcium chelation, which is also required for normal mucin unfolding. Since bicarbonate secretion is impaired in CF, leading to insufficient mucin unfolding and thereby attached mucus, and since bicarbonate has the ability to bind calcium, we hypothesized that the calcium chelating property of OligoG would lead to detachment of CF mucus. Indeed, OligoG could compete with the N-terminus of the MUC2 mucin for calcium binding as shown by microscale thermophoresis. Further, effects on mucus thickness and attachment induced by OligoG and other alginate fractions of different length and composition were evaluated in explants of CF mouse ileum mounted in horizontal Ussing-type chambers. OligoG at 1.5% caused effective detachment of CF mucus and the most potent alginate fraction tested, the poly-G fraction of about 12 residues, had similar potency compared to OligoG whereas mannuronate-rich (M) polymers had minimal effect. In conclusion, OligoG binds calcium with appropriate affinity without any overt harmful effect on the tissue and can be exploited for treating mucus stagnation. © 2017 John Wiley & Sons Australia, Ltd.

  3. Respiratory exacerbation in a young adult with cystic fibrosis and tricuspid atresia.

    PubMed

    Wood, Jamie; Sawyer, Abbey; Mulrennan, Siobhain; Bullock, Andrew

    2018-07-01

    Tricuspid atresia (TAt) is a complex congenital heart defect (CHD) characterized by the absence of the tricuspid valve and right ventricular hypoplasia requiring surgery in childhood, the Fontan procedure. We present a case of a 21-year-old male with TAt and cystic fibrosis (CF), who underwent a Fontan procedure in childhood, presenting to an adult CF clinic with severe deterioration in his respiratory status and multi-organ dysfunction associated with CF. This report describes problems associated with the management of a CF respiratory exacerbation and extrapulmonary manifestations of CF in the unique situation of a Fontan circulation, a circulation with absence of a subpulmonary ventricle and pulsatile pulmonary arterial blood flow where maintenance of systemic cardiac output is totally dependent on good respiratory function and low pulmonary artery pressures.

  4. Expression and function of orphan nuclear receptor TLX in adult neural stem cells.

    PubMed

    Shi, Yanhong; Chichung Lie, D; Taupin, Philippe; Nakashima, Kinichi; Ray, Jasodhara; Yu, Ruth T; Gage, Fred H; Evans, Ronald M

    2004-01-01

    The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains and is highly expressed in the adult brain. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behaviour. Here we show that TLX maintains adult neural stem cells in an undifferentiated, proliferative state. We show that TLX-expressing cells isolated by fluorescence-activated cell sorting (FACS) from adult brains can proliferate, self-renew and differentiate into all neural cell types in vitro. By contrast, TLX-null cells isolated from adult mutant brains fail to proliferate. Reintroducing TLX into FACS-sorted TLX-null cells rescues their ability to proliferate and to self-renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells.

  5. Highly-stable and -flexible graphene/(CF3SO2)2NH/graphene transparent conductive electrodes for organic solar cells

    NASA Astrophysics Data System (ADS)

    Seo, Sang Woo; Lee, Ha Seung; Shin, Dong Hee; Kim, Ju Hwan; Jang, Chan Wook; Kim, Jong Min; Kim, Sung; Choi, Suk-Ho

    2017-10-01

    We first employ highly-stable and -flexible (CF3SO2)2NH-doped graphene (TFSA/GR) and GR-encapsulated TFSA/GR (GR/TFSA/GR) transparent conductive electrodes (TCEs) prepared on polyethylene terephthalate substrates for flexible organic solar cells (OSCs). Compared to conventional indium tin oxide (ITO) TCEs, the TFSA-doped-GR TCEs show higher optical transmittance and larger sheet resistance. The TFSA/GR and GR/TFSA/GR TCEs show work functions of 4.89 ± 0.16 and 4.97 ± 0.18 eV, respectively, which are not only larger than those of the ITO TCEs but also indicate p-type doping of GR, and are therefore more suitable for anode TCEs of OSCs. In addition, typical GR/TFSA/GR-TCE OSCs are much more mechanically flexible than the ITO-TCE ones with their photovoltaic parameters being similar, as proved by bending tests as functions of cycle and curvature.

  6. Barriers to carrier testing for adult cystic fibrosis sibs: the importance of not knowing.

    PubMed

    Fanos, J H; Johnson, J P

    1995-10-23

    Early experience in centers offering population screening for cystic fibrosis (CF) has shown that few of the public are taking advantage of the offer [Miller, 1993: New Scientist 139:6]. There is similar low utilization among adult CF sibs [Fanos and Johnson, 1993: Am J Hum Genet 53:A51]. The purpose of this study was to identify factors motivating or interfering with the pursuit of carrier testing in adult CF sibs. Eighty-four adult CF sibs and their spouses, drawn from Children's Hospital, Oakland, CA, and Children's Hospital, Boston, MA, were interviewed for about an hour, and qualitative material was coded on various themes. Structural and psychological barriers to the transmission of genetic information were identified: 1) sibs encountered difficulty in obtaining information concerning availability of testing; 2) parental guilt and blame prevents parents from discussing genetic issues with the sib; 3) sibs rarely discuss testing with each other; 4) the CF patient or parent often has difficulty with the implications of the sib seeking carrier testing; 5) family and individual myths about carrier status influence the sib's decision to seek testing; 6) statistical odds have lost meaning in families where the rare has already occurred; 7) the sib fears loss of interpersonal desirability; and 8) carrier status can serve an important function in binding guilt. Remaining unaware of their carrier status may serve significant psychological functions for individuals at risk.

  7. The longest telomeres: a general signature of adult stem cell compartments

    PubMed Central

    Flores, Ignacio; Canela, Andres; Vera, Elsa; Tejera, Agueda; Cotsarelis, George; Blasco, María A.

    2008-01-01

    Identification of adult stem cells and their location (niches) is of great relevance for regenerative medicine. However, stem cell niches are still poorly defined in most adult tissues. Here, we show that the longest telomeres are a general feature of adult stem cell compartments. Using confocal telomere quantitative fluorescence in situ hybridization (telomapping), we find gradients of telomere length within tissues, with the longest telomeres mapping to the known stem cell compartments. In mouse hair follicles, we show that cells with the longest telomeres map to the known stem cell compartments, colocalize with stem cell markers, and behave as stem cells upon treatment with mitogenic stimuli. Using K15-EGFP reporter mice, which mark hair follicle stem cells, we show that GFP-positive cells have the longest telomeres. The stem cell compartments in small intestine, testis, cornea, and brain of the mouse are also enriched in cells with the longest telomeres. This constitutes the description of a novel general property of adult stem cell compartments. Finally, we make the novel finding that telomeres shorten with age in different mouse stem cell compartments, which parallels a decline in stem cell functionality, suggesting that telomere loss may contribute to stem cell dysfunction with age. PMID:18283121

  8. ESKAPE/CF: A Knowledge Acquisition Tool for Expert Systems Using Cognitive Feedback

    DTIC Science & Technology

    1991-03-01

    NAVAL POSTGRADUATE SCHOOL Monterey, California AD-A241 815i!1! lit 1i iill 1111 !! I 1111 ST E * ODTIC OCT22 z 99I; THESIS ESKAPE /CF: A KNOWLEDGE...11. TITLE (include Security Classification) ESKAPE /CF: A KNOWLEDGE ACQUISITION TOOL FOR EXPERT SYSTEMS USING COGNITIVE FEEDBACK (U) e PERSOIAL AUTVR(Yl...tool using Cognitive Feedback ( ESKAPE /CF), based on Lens model techniques which have demonstrated effectiveness in cap- turing policy knowledge. The

  9. TERT promoter mutation in adult granulosa cell tumor of the ovary.

    PubMed

    Pilsworth, Jessica A; Cochrane, Dawn R; Xia, Zhouchunyang; Aubert, Geraldine; Färkkilä, Anniina E M; Horlings, Hugo M; Yanagida, Satoshi; Yang, Winnie; Lim, Jamie L P; Wang, Yi Kan; Bashashati, Ali; Keul, Jacqueline; Wong, Adele; Norris, Kevin; Brucker, Sara Y; Taran, Florin-Andrei; Krämer, Bernhard; Staebler, Annette; Oliva, Esther; Shah, Sohrab P; Kommoss, Stefan; Kommoss, Friedrich; Gilks, C Blake; Baird, Duncan M; Huntsman, David G

    2018-02-15

    The telomerase reverse transcriptase (TERT) gene is highly expressed in stem cells and silenced upon differentiation. Cancer cells can attain immortality by activating TERT to maintain telomere length and telomerase activity, which is a crucial step of tumorigenesis. Two somatic mutations in the TERT promoter (C228T; C250T) have been identified as gain-of-function mutations that promote transcriptional activation of TERT in multiple cancers, such as melanoma and glioblastoma. A recent study investigating TERT promoter mutations in ovarian carcinomas found C228T and C250T mutations in 15.9% of clear cell carcinomas. However, it is unknown whether these mutations are frequent in other ovarian cancer subtypes, in particular, sex cord-stromal tumors including adult granulosa cell tumors. We performed whole-genome sequencing on ten adult granulosa cell tumors with matched normal blood and identified a TERT C228T promoter mutation in 50% of tumors. We found that adult granulosa cell tumors with mutated TERT promoter have increased expression of TERT mRNA and exhibited significantly longer telomeres compared to those with wild-type TERT promoter. Extension cohort analysis using allelic discrimination revealed the TERT C228T mutation in 51 of 229 primary adult granulosa cell tumors (22%), 24 of 58 recurrent adult granulosa cell tumors (41%), and 1 of 22 other sex cord-stromal tumors (5%). There was a significant difference in overall survival between patients with TERT C228T promoter mutation in the primary tumors and those without it (p = 0.00253, log-rank test). In seven adult granulosa cell tumors, we found the TERT C228T mutation present in recurrent tumors and absent in the corresponding primary tumor. Our data suggest that TERT C228T promoter mutations may have an important role in progression of adult granulosa cell tumors.

  10. The altered gut microbiota in adults with cystic fibrosis.

    PubMed

    Burke, D G; Fouhy, F; Harrison, M J; Rea, M C; Cotter, P D; O'Sullivan, O; Stanton, C; Hill, C; Shanahan, F; Plant, B J; Ross, R P

    2017-03-09

    Cystic Fibrosis (CF) is an autosomal recessive disease that affects the function of a number of organs, principally the lungs, but also the gastrointestinal tract. The manifestations of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in the gastrointestinal tract, as well as frequent antibiotic exposure, undoubtedly disrupts the gut microbiota. To analyse the effects of CF and its management on the microbiome, we compared the gut microbiota of 43 individuals with CF during a period of stability, to that of 69 non-CF controls using 454-pyrosequencing of the 16S rRNA gene. The impact of clinical parameters, including antibiotic therapy, on the results was also assessed. The CF-associated microbiome had reduced microbial diversity, an increase in Firmicutes and a reduction in Bacteroidetes compared to the non-CF controls. While the greatest number of differences in taxonomic abundances of the intestinal microbiota was observed between individuals with CF and the healthy controls, gut microbiota differences were also reported between people with CF when grouped by clinical parameters including % predicted FEV 1 (measure of lung dysfunction) and the number of intravenous (IV) antibiotic courses in the previous 12 months. Notably, CF individuals presenting with severe lung dysfunction (% predicted FEV 1  ≤ 40%) had significantly (p < 0.05) reduced gut microbiota diversity relative to those presenting with mild or moderate dysfunction. A significant negative correlation (-0.383, Simpson's Diversity Index) was also observed between the number of IV antibiotic courses and gut microbiota diversity. This is one of the largest single-centre studies on gut microbiota in stable adults with CF and demonstrates the significantly altered gut microbiota, including reduced microbial diversity seen in CF patients compared to healthy controls. The data show the impact that CF and it's management have on gut microbiota, presenting the opportunity to

  11. Walking Stability during Cell Phone Use in Healthy Adults

    PubMed Central

    Kao, Pei-Chun; Higginson, Christopher I.; Seymour, Kelly; Kamerdze, Morgan; Higginson, Jill S.

    2015-01-01

    The number of falls and/or accidental injuries associated with cellular phone use during walking is growing rapidly. Understanding the effects of concurrent cell phone use on human gait may help develop safety guidelines for pedestrians. It was shown previously that older adults had more pronounced dual-task interferences than younger adults when concurrent cognitive task required visual information processing. Thus, cell phone use might have greater impact on walking stability in older than in younger adults. This study examined gait stability and variability during a cell phone dialing task (phone) and two classic cognitive tasks, the Paced Auditory Serial Addition Test (PASAT) and Symbol Digit Modalities Test (SDMT). Nine older and seven younger healthy adults walked on a treadmill at four different conditions: walking only, PASAT, phone, and SDMT. We computed short-term local divergence exponent (LDE) of the trunk motion (local stability), dynamic margins of stability (MOS), step spatiotemporal measures, and kinematic variability. Older and younger adults had similar values of short-term LDE during all conditions, indicating that local stability was not affected by the dual-task. Compared to walking only, older and younger adults walked with significantly greater average mediolateral MOS during phone and SDMT conditions but significantly less ankle angle variability during all dual-tasks and less knee angle variability during PASAT. The current findings demonstrate that healthy adults may try to control foot placement and joint kinematics during cell phone use or another cognitive task with a visual component to ensure sufficient dynamic margins of stability and maintain local stability. PMID:25890490

  12. Metabolic alkalosis contributes to acute hypercapnic respiratory failure in adult cystic fibrosis.

    PubMed

    Holland, Anne E; Wilson, John W; Kotsimbos, Thomas C; Naughton, Matthew T

    2003-08-01

    and study objectives: Patients with end-stage cystic fibrosis (CF) develop respiratory failure and hypercapnia. In contrast to COPD patients, altered electrolyte transport and malnutrition in CF patients may predispose them to metabolic alkalosis and, therefore, may contribute to hypercapnia. The aim of this study was to determine the prevalence of metabolic alkalosis in adults with hypercapnic respiratory failure in the setting of acute exacerbations of CF compared with COPD. Levels of arterial blood gases, plasma electrolytes, and serum albumin from 14 consecutive hypercapnic CF patients who had been admitted to the hospital with a respiratory exacerbation were compared with 49 consecutive hypercapnic patients with exacerbations of COPD. Hypercapnia was defined as a PaCO(2) of > or = 45 mm Hg. Despite similar PaCO(2) values, patients in the CF group were significantly more alkalotic than were those in the COPD group (mean [+/- SD] pH, 7.43 +/- 0.03 vs 7.37 +/- 0.05, respectively; p < 0.01). A mixed respiratory acidosis and metabolic alkalosis was evident in 71% of CF patients and 22% of COPD patients (p < 0.01). The mean concentrations of plasma chloride (95.1 +/- 4.9 vs 99.8 +/- 5.2 mmol/L, respectively; p < 0.01) and sodium (136.5 +/- 2.8 vs 140.4 +/- 4.5 mmol/L, respectively; p < 0.01) were significantly lower in the CF group, and the levels of serum albumin were significantly reduced (27.4 +/- 5.8 vs 33.7 +/- 4.8 mmol/L, respectively; p < 0.01). Metabolic alkalosis contributes to hypercapnic respiratory failure in adults with acute exacerbations of CF. This acid-base disturbance occurs in conjunction with reduced total body salt levels and hypoalbuminemia.

  13. Calcium-loaded 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid blocks cell-to-cell diffusion of carboxyfluorescein in staminal hairs of Setcreasea purpurea.

    PubMed

    Tucker, E B

    1990-08-01

    The effect of microinjected calcium-loaded 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (CaBAPTA) on cell-to-cell diffusion of carboxyfluorescein (CF) was examined in staminal hairs of S. purpurea Boom. The CaBAPTA was microinjected into the cytoplasm of the staminal hairs either with CF or prior to a subsequent microinjection of CF. The cell-to-cell diffusion of CF along the hair was monitored using enhanced-fluorescence video microscopy. Cytoplasmic streaming stopped in cells treated with CaBAPTA, indicating that intracellular Ca(2+) had increased. Cell-to-cell diffusion of CF was blocked in cells treated with Ca-BAPTA. An inhibition of cytoplasmic streaming and cell-to-cell diffusion was observed in the cells adjoining the CaBAPTA-microinjected cell, indicating that the Ca-BAPTA appeared to pass through plasmodesmata. While cytoplasmic streaming resumed 5-10 min after CaBAPTA treatment, cell-to-cell diffusion did not resume until 30-120 min later. These data support an involvement of calcium in the regulation of cell-to-cell communication in plants.

  14. Brome isotope selective control of CF3Br molecule clustering by IR laser radiation in gas-dynamic expansion of CF3Br - Ar mixture

    NASA Astrophysics Data System (ADS)

    Apatin, V. M.; Lokhman, V. N.; Makarov, G. N.; Ogurok, N.-D. D.; Ryabov, E. A.

    2018-02-01

    We report the results of research on the experimental control of CF3Br molecule clustering under gas-dynamic expansion of the CF3Br - Ar mixture at a nozzle exit by using IR laser radiation. A cw CO2 laser is used for exciting molecules and clusters in the beam and a time-of-flight mass-spectrometer with laser UV ionisation of particles for their detection. The parameters of the gas above the nozzle are determined (compositions and pressure) at which intensive molecule clustering occurs. It is found that in the case of the CF3Br gas without carrier when the pressure P0 above the nozzle does not exceed 4 atm, molecular clusters actually are not generated in the beam. If the gas mixture of CF3Br with argon is used at a pressure ratio 1 : N, where N >= 3, and the total pressure above the nozzle is P0 >= 2 atm, then there occurs molecule clustering. We study the dependences of the efficiency of suppressing the molecule clustering on parameters of the exciting pulse, gas parameters above the nozzle, and on a distance of the molecule irradiation zone from the nozzle exit section. It is shown that in the case of resonant vibrational excitation of gas-dynamically cooled CF3Br molecules at the nozzle exit one can realise isotope-selective suppression of molecule clustering with respect to bromine isotopes. With the CF3Br - Ar mixtures having the pressure ratio 1 : 3 and 1 : 15, the enrichment factors obtained with respect to bromine isotopes are kenr ≈ 1.05 ± 0.005 and kenr ≈ 1.06 ± 0.007, respectively, under jet irradiation by laser emission in the 9R(30) line (1084.635 cm-1). The results obtained let us assume that this method can be used to control clustering of molecules comprising heavy element isotopes, which have a small isotopic shift in IR absorption spectra.

  15. Oxidative trifluoromethylation and trifluoromethylthiolation reactions using (trifluoromethyl)trimethylsilane as a nucleophilic CF3 source.

    PubMed

    Chu, Lingling; Qing, Feng-Ling

    2014-05-20

    The trifluoromethyl group is widely prevalent in many pharmaceuticals and agrochemicals because its incorporation into drug candidates could enhance chemical and metabolic stability, improve lipophilicity and bioavailability, and increase the protein bind affinity. Consequently, extensive attention has been devoted toward the development of efficient and versatile methods for introducing the CF3 group into various organic molecules. Direct trifluoromethylation reaction has become one of the most efficient and important approaches for constructing carbon-CF3 bonds. Traditionally, the nucleophilic trifluoromethylation reaction involves an electrophile and the CF3 anion, while the electrophilic trifluoromethylation reaction involves a nucleophile and the CF3 cation. In 2010, we proposed the concept of oxidative trifluoromethylation: the reaction of nucleophilic substrates and nucleophilic trifluoromethylation reagents in the presence of oxidants. In this Account, we describe our recent studies of oxidative trifluoromethylation reactions of various nucleophiles with CF3SiMe3 in the presence of oxidants. We have focused most of our efforts on constructing carbon-CF3 bonds via direct trifluoromethylation of various C-H bonds. We have demonstrated copper-mediated or -catalyzed or metal-free oxidative C-H trifluoromethylation of terminal alkynes, tertiary amines, arenes and heteroarenes, and terminal alkenes. Besides various C-H bonds, aryl boronic acids proved to be viable nucleophilic coupling partners for copper-mediated or -catalyzed cross-coupling reactions with CF3SiMe3. To further expand the reaction scope, we also applied H-phosphonates to the oxidative trifluoromethylation system to construct P-CF3 bonds. Most recently, we developed silver-catalyzed hydrotrifluoromethylation of unactivated olefins. These studies explore boronic acids, C-H bonds, and P-H bonds as novel nucleophiles in transition-metal-mediated or -catalyzed cross-coupling reactions with CF3SiMe3

  16. Stem cell sources for clinical islet transplantation in type 1 diabetes: embryonic and adult stem cells.

    PubMed

    Miszta-Lane, Helena; Mirbolooki, Mohammadreza; James Shapiro, A M; Lakey, Jonathan R T

    2006-01-01

    Lifelong immunosuppressive therapy and inadequate sources of transplantable islets have led the islet transplantation benefits to less than 0.5% of type 1 diabetics. Whereas the potential risk of infection by animal endogenous viruses limits the uses of islet xeno-transplantation, deriving islets from stem cells seems to be able to overcome the current problems of islet shortages and immune compatibility. Both embryonic (derived from the inner cell mass of blastocysts) and adult stem cells (derived from adult tissues) have shown controversial results in secreting insulin in vitro and normalizing hyperglycemia in vivo. ESCs research is thought to have much greater developmental potential than adult stem cells; however it is still in the basic research phase. Existing ESC lines are not believed to be identical or ideal for generating islets or beta-cells and additional ESC lines have to be established. Research with ESCs derived from humans is controversial because it requires the destruction of a human embryo and/or therapeutic cloning, which some believe is a slippery slope to reproductive cloning. On the other hand, adult stem cells are already in some degree specialized, recipients may receive their own stem cells. They are flexible but they have shown mixed degree of availability. Adult stem cells are not pluripotent. They may not exist for all organs. They are difficult to purify and they cannot be maintained well outside the body. In order to draw the future avenues in this field, existent discrepancies between the results need to be clarified. In this study, we will review the different aspects and challenges of using embryonic or adult stem cells in clinical islet transplantation for the treatment of type 1 diabetes.

  17. Divalent and trivalent gas-phase coordination complexes of californium: evaluating the stability of Cf(II)

    DOE PAGES

    Dau, Phuong D.; Shuh, David K.; Sturzbecher-Hoehne, Manuel; ...

    2016-07-07

    The divalent oxidation state is increasingly stable relative to the trivalent state for the later actinide elements, with californium the first actinide to exhibit divalent chemistry under moderate conditions. Although there is evidence for divalent Cf in solution and solid compounds, there are no reports of discrete complexes in which Cf II is coordinated by anionic ligands. Described here is the divalent Cf methanesulfinate coordination complex, Cf II(CH 3SO 2) 3-, prepared in the gas phase by reductive elimination of CH 3SO 2 from Cf III(CH 3SO 2) 4-. Comparison with synthesis of the corresponding Sm and Cm complexes revealsmore » reduction of CfIII and SmIII, and no evidence for reduction of Cm III. This reflects the comparative 3+/2+ reduction potentials: Cf 3+ (-1.60 V) ≈ Sm 3+ (-1.55 V) >> Cm 3+ (-3.7 V). Association of O 2 to the divalent complexes is attributed to formation of superoxides, with recovery of the trivalent oxidation state. Lastly, the new gas-phase chemistry of californium, now the heaviest element to have been studied in this manner, provides evidence for Cf II coordination complexes and similar chemistry of Cf and Sm.« less

  18. Divalent and trivalent gas-phase coordination complexes of californium: evaluating the stability of Cf(II)

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

    Dau, Phuong D.; Shuh, David K.; Sturzbecher-Hoehne, Manuel

    The divalent oxidation state is increasingly stable relative to the trivalent state for the later actinide elements, with californium the first actinide to exhibit divalent chemistry under moderate conditions. Although there is evidence for divalent Cf in solution and solid compounds, there are no reports of discrete complexes in which Cf II is coordinated by anionic ligands. Described here is the divalent Cf methanesulfinate coordination complex, Cf II(CH 3SO 2) 3-, prepared in the gas phase by reductive elimination of CH 3SO 2 from Cf III(CH 3SO 2) 4-. Comparison with synthesis of the corresponding Sm and Cm complexes revealsmore » reduction of CfIII and SmIII, and no evidence for reduction of Cm III. This reflects the comparative 3+/2+ reduction potentials: Cf 3+ (-1.60 V) ≈ Sm 3+ (-1.55 V) >> Cm 3+ (-3.7 V). Association of O 2 to the divalent complexes is attributed to formation of superoxides, with recovery of the trivalent oxidation state. Lastly, the new gas-phase chemistry of californium, now the heaviest element to have been studied in this manner, provides evidence for Cf II coordination complexes and similar chemistry of Cf and Sm.« less

  19. Ab-initio study of the energetics and thermodynamics of the reaction CH3H + O( 3P) → CF3H … O → CF3 + OH

    NASA Astrophysics Data System (ADS)

    Kreye, W. C.

    1996-07-01

    Ab-initio computations at 298.15 K were made of the activation quantities ΔH ‡, ΔS ‡, and ΔG ‡ and of the reaction quantities ΔHr and ΔSr for CF3H + O( 3P) → CF3H … O → .CF3.OH. CF 3H … O is the transition state (TS). GAUSSIAN92 was used and energies computed at a slightly modified Gaussian-2 level. Two potential surfaces for the TS had symmetries 3A' and 3A″. The two rate constants included a semi-classical, quantum-mechanical-tunneling transmission coefficient. The ab-initio ΔH ‡and ΔH r values were in excellent agreement (± 1 kcal/mol) with experiment; but the ΔS ‡, ΔG ‡, and ΔS r values yielded somewhat poorer agreement. Experimental and ab-initio structures were in excellent agreement.

  20. Avr4 promotes Cf-4 receptor-like protein association with the BAK1/SERK3 receptor-like kinase to initiate receptor endocytosis and plant immunity.

    PubMed

    Postma, Jelle; Liebrand, Thomas W H; Bi, Guozhi; Evrard, Alexandre; Bye, Ruby R; Mbengue, Malick; Kuhn, Hannah; Joosten, Matthieu H A J; Robatzek, Silke

    2016-04-01

    The first layer of plant immunity is activated by cell surface receptor-like kinases (RLKs) and proteins (RLPs) that detect infectious pathogens. Constitutive interaction with the SUPPRESSOR OF BIR1 (SOBIR1) RLK contributes to RLP stability and kinase activity. As RLK activation requires transphosphorylation with a second associated RLK, it remains elusive how RLPs initiate downstream signaling. We employed live-cell imaging, gene silencing and coimmunoprecipitation to investigate the requirement of associated kinases for functioning and ligand-induced subcellular trafficking of Cf RLPs that mediate immunity of tomato against Cladosporium fulvum. Our research shows that after elicitation with matching effector ligands Avr4 and Avr9, BRI1-ASSOCIATED KINASE 1/SOMATIC EMBRYOGENESIS RECEPTOR KINASE 3 (BAK1/SERK3) associates with Cf-4 and Cf-9. BAK1/SERK3 is required for the effector-triggered hypersensitive response and resistance of tomato against C. fulvum. Furthermore, Cf-4 interacts with SOBIR1 at the plasma membrane and is recruited to late endosomes upon Avr4 trigger, also depending on BAK1/SERK3. These observations indicate that RLP-mediated resistance and endocytosis require ligand-induced recruitment of BAK1/SERK3, reminiscent of BAK1/SERK3 interaction and subcellular fate of the FLAGELLIN SENSING 2 (FLS2) RLK. This reveals that diverse classes of cell surface immune receptors share common requirements for initiation of resistance and endocytosis. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  1. Cerebellar stem cells do not produce neurons and astrocytes in adult mouse

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

    Su, Xin; Guan, Wuqiang; Yu, Yong-Chun

    Highlights: • No new neurons and astrocytes are generated in adult mouse cerebellum. • Very few mash1{sup +} or nestin{sup +} stem cells exist, and most of them are quiescent. • Cell proliferation rate is diversified among cerebellar regions and decreases over time. - Abstract: Although previous studies implied that cerebellar stem cells exist in some adult mammals, little is known about whether these stem cells can produce new neurons and astrocytes. In this study by bromodeoxyuridine (BrdU) intraperitoneal (i.p.) injection, we found that there are abundant BrdU{sup +} cells in adult mouse cerebellum, and their quantity and density decreasesmore » significantly over time. We also found cell proliferation rate is diversified in different cerebellar regions. Among these BrdU{sup +} cells, very few are mash1{sup +} or nestin{sup +} stem cells, and the vast majority of cerebellar stem cells are quiescent. Data obtained by in vivo retrovirus injection indicate that stem cells do not produce neurons and astrocytes in adult mouse cerebellum. Instead, some cells labeled by retrovirus are Iba1{sup +} microglia. These results indicate that very few stem cells exist in adult mouse cerebellum, and none of these stem cells contribute to neurogenesis and astrogenesis under physiological condition.« less

  2. Diet of Physalaemus cf. cicada (Leptodactylidae) and Bufo granulosus (Bufonidae) in a semideciduous forest.

    PubMed

    Santana, A S; Juncá, F A

    2007-02-01

    We determined the diet of the two most abundant anuran species which occur in the litter of a semideciduous forest (Lençóis, Bahia, Brazil), Physalaemus cf. cicada and Bufo granulosus in the dry and rainy seasons. Pitfall traps were used to collect anuran and invertebrate fauna, which showed the availability of prey in the environment. Physalaemus cf. cicada was present in both seasons and Bufo granulosus only in the rainy season. Both species fed mainly on Isoptera and Formicidae. However, there is a difference between the rainy and dry seasons concerning the diet of P. cf. cicada. During the rainy season P. cf. cicada consumed less Isoptera and more Formicidae than in the dry season. In the volumetric sense, Orthoptera was the most important alimentary category for P. cf. cicada and B. granulosus. The Jacobs electivity index indicated that Physalaemus cf. cicada and Bufo granulosus were specialists in Isoptera.

  3. Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells

    PubMed Central

    Stanton, Bruce A.; Coutermarsh, Bonita; Barnaby, Roxanna; Hogan, Deborah

    2015-01-01

    Background P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and thereby reduces the clinical efficacy of VX-809 + VX-770. Methods and Results F508del-CFBE cells and primary cultures of CF-HBE cells (F508del/F508del) were exposed to VX-809 alone or a combination of VX-809 + VX-770 for 48 hours and the effect of P. aeruginosa on F508del-CFTR Cl secretion was measured in Ussing chambers. The effect of VX-809 on F508del-CFTR abundance was measured by cell surface biotinylation and western blot analysis. PAO1, PA14, PAK and 6 clinical isolates of P. aeruginosa (3 mucoid and 3 non-mucoid) significantly reduced drug stimulated F508del-CFTR Cl secretion, and plasma membrane F508del-CFTR. Conclusion The observation that P. aeruginosa reduces VX-809 and VX-809 + VX-770 stimulated F508del CFTR Cl secretion may explain, in part, why VX-809 + VX-770 has modest efficacy in clinical trials. PMID:26018799

  4. Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells.

    PubMed

    Stanton, Bruce A; Coutermarsh, Bonita; Barnaby, Roxanna; Hogan, Deborah

    2015-01-01

    P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and thereby reduces the clinical efficacy of VX-809 + VX-770. F508del-CFBE cells and primary cultures of CF-HBE cells (F508del/F508del) were exposed to VX-809 alone or a combination of VX-809 + VX-770 for 48 hours and the effect of P. aeruginosa on F508del-CFTR Cl secretion was measured in Ussing chambers. The effect of VX-809 on F508del-CFTR abundance was measured by cell surface biotinylation and western blot analysis. PAO1, PA14, PAK and 6 clinical isolates of P. aeruginosa (3 mucoid and 3 non-mucoid) significantly reduced drug stimulated F508del-CFTR Cl secretion, and plasma membrane F508del-CFTR. The observation that P. aeruginosa reduces VX-809 and VX-809 + VX-770 stimulated F508del CFTR Cl secretion may explain, in part, why VX-809 + VX-770 has modest efficacy in clinical trials.

  5. Exosome and Microvesicle-Enriched Fractions Isolated from Mesenchymal Stem Cells by Gradient Separation Showed Different Molecular Signatures and Functions on Renal Tubular Epithelial Cells.

    PubMed

    Collino, Federica; Pomatto, Margherita; Bruno, Stefania; Lindoso, Rafael Soares; Tapparo, Marta; Sicheng, Wen; Quesenberry, Peter; Camussi, Giovanni

    2017-04-01

    Several studies have suggested that extracellular vesicles (EVs) released from mesenchymal stem cells (MSCs) may mediate MSC paracrine action on kidney regeneration. This activity has been, at least in part, ascribed to the transfer of proteins/transcription factors and different RNA species. Information on the RNA/protein content of different MSC EV subpopulations and the correlation with their biological activity is currently incomplete. The aim of this study was to evaluate the molecular composition and the functional properties on renal target cells of MSC EV sub-populations separated by gradient floatation. The results demonstrated heterogeneity in quantity and composition of MSC EVs. Two peaks of diameter were observed (90-110 and 170-190 nm). The distribution of exosomal markers and miRNAs evaluated in the twelve gradient fractions showed an enrichment in fractions with a flotation density of 1.08-1.14 g/mL. Based on this observation, we evaluated the biological activity on renal cell proliferation and apoptosis resistance of low (CF1), medium (CF2) and high (CF3) floatation density fractions. EVs derived from all fractions, were internalized by renal cells, CF1 and CF2 but not CF3 fraction stimulated significant cell proliferation. CF2 also inhibited apoptosis on renal tubular cells submitted to ischemia-reperfusion injury. Comparative miRNomic and proteomic profiles reveal a cluster of miRNAs and proteins common to all three fractions and an enrichment of selected molecules related to renal regeneration in CF2 fraction. In conclusion, the CF2 fraction enriched in exosomal markers was the most active on renal tubular cell proliferation and protection from apoptosis.

  6. Characterization of Insulin-Immunoreactive Cells and Endocrine Cells Within the Duct System of the Adult Human Pancreas.

    PubMed

    Li, Rong; Zhang, Xiaoxi; Yu, Lan; Zou, Xia; Zhao, Hailu

    2016-01-01

    The adult pancreatic duct system accommodates endocrine cells that have the potential to produce insulin. Here we report the characterization and distribution of insulin-immunoreactive cells and endocrine cells within the ductal units of adult human pancreas. Sequential pancreas sections from 12 nondiabetic adults were stained with biomarkers of ductal epithelial cells (cytokeratin 19), acinar cells (amylase), endocrine cells (chromogranin A; neuron-specific enolase), islet hormones (insulin, glucagon, somatostatin, pancreatic polypeptide), cell proliferation (Ki-67), and neogenesis (CD29). The number of islet hormone-immunoreactive cells increased from large ducts to the terminal branches. The insulin-producing cells outnumbered endocrine cells reactive for glucagon, somatostatin, or pancreatic polypeptide. The proportions of insulin-immunoreactive count compared with local islets (100% as a baseline) were 1.5% for the main ducts, 7.2% for interlobular ducts, 24.8% for intralobular ducts, 67.9% for intercalated ducts, and 348.9% for centroacinar cells. Both Ki-67- and CD29-labeled cells were predominantly localized in the terminal branches around the islets. The terminal branches also showed cells coexpressing islet hormones and cytokeratin 19. The adult human pancreatic ducts showed islet hormone-producing cells. The insulin-reactive cells predominantly localized in terminal branches where they may retain potential capability for β-cell neogenesis.

  7. Anonymous sources: where do adult β cells come from?

    PubMed Central

    German, Michael S.

    2013-01-01

    Evidence that the pool of insulin-producing β cells in the pancreas is reduced in both major forms of diabetes mellitus has led to efforts to understand β cell turnover in the adult pancreas. Unfortunately, previous studies have reached opposing conclusions regarding the source of new β cells during regeneration in the adult pancreas. In this issue of the JCI, Xiao et al. use a novel mouse model for detecting new β cells derived from non–β cells to demonstrate the absence of β cell neogenesis from non–β cells during normal postnatal growth and in models of β cell regeneration. This work adds to mounting evidence that in most physiological and pathological conditions, β cell neogenesis may not make large contributions to the postnatal β cell pool — at least not in rodents. PMID:23619356

  8. Corrosion of Continuous Fiber Reinforced Aluminum Metal Matrix Composites (CF-AMCs)

    NASA Astrophysics Data System (ADS)

    Tiwari, Shruti

    The first objective of this research is to study the atmospheric corrosion behavior of continuous reinforced aluminum matrix composites (CF-AMCs). The materials used for this research were alumina (Al2O3) and nickel (Ni) coated carbon (C) fibers reinforced AMCs. The major focus is to identify the correlation between atmospheric parameters and the corrosion rates of CF-AMCs in the multitude of microclimates and environments in Hawai'i. The micro-structures of CF-AMCs were obtained to correlate the microstructures with their corrosion performances. Also electrochemical polarization experiments were conducted in the laboratory to explain the corrosion mechanism of CF-AMCs. In addition, CF-AMCs were exposed to seven different test sites for three exposure periods. The various climatic conditions like temperature (T), relative humidity (RH), rainfall (RF), time of wetness (TOW), chloride (Cl- ) and sulfate (SO42-) deposition rate, and pH were monitored for three exposure period. Likewise, mass losses of CF-AMCs at each test site for three exposure periods were determined. The microstructure of the CF-AMCS showed that Al/C/50f MMCs contained a Ni-rich phase in the matrix, indicating that the Ni coating on the C fiber dissolved in the matrix. The intermetallic phases obtained in Al-2wt% Cu/Al 2O3/50f-T6 MMC and Al-2wt%-T6 monolith were rich in Cu and Fe. The intermetallic phases obtained in Al 7075/Al2O3/50f-T6 MMC and Al 7075-T6 monolith also contained traces of Mg, Zn, Ni, and Si. Electrochemical polarization experiment indicated that the Al/Al 2O3/50f Al-2wt% Cu/Al2O3/50f-T6 and Al 7075/Al2O3/50f-T6 MMC showed similar corrosion trends as their respective monoliths pure Al, Al-2wt%-T6 and Al 7075-T6 in both aerated and deaerated condition. Al2O3 fiber, being an insulator, did not have a great effect on the polarization behavior of the composites. Al/C/50f MMCs corroded at a much faster rate as compared to pure Al monolith due to the galvanic effect between C and Al

  9. Neural stem/progenitor cell properties of glial cells in the adult mouse auditory nerve

    PubMed Central

    Lang, Hainan; Xing, Yazhi; Brown, LaShardai N.; Samuvel, Devadoss J.; Panganiban, Clarisse H.; Havens, Luke T.; Balasubramanian, Sundaravadivel; Wegner, Michael; Krug, Edward L.; Barth, Jeremy L.

    2015-01-01

    The auditory nerve is the primary conveyor of hearing information from sensory hair cells to the brain. It has been believed that loss of the auditory nerve is irreversible in the adult mammalian ear, resulting in sensorineural hearing loss. We examined the regenerative potential of the auditory nerve in a mouse model of auditory neuropathy. Following neuronal degeneration, quiescent glial cells converted to an activated state showing a decrease in nuclear chromatin condensation, altered histone deacetylase expression and up-regulation of numerous genes associated with neurogenesis or development. Neurosphere formation assays showed that adult auditory nerves contain neural stem/progenitor cells (NSPs) that were within a Sox2-positive glial population. Production of neurospheres from auditory nerve cells was stimulated by acute neuronal injury and hypoxic conditioning. These results demonstrate that a subset of glial cells in the adult auditory nerve exhibit several characteristics of NSPs and are therefore potential targets for promoting auditory nerve regeneration. PMID:26307538

  10. Evidence for crustal degassing of CF4 and SF6 in Mojave Desert groundwaters

    USGS Publications Warehouse

    Deeds, D.A.; Vollmer, M.K.; Kulongoski, J.T.; Miller, B.R.; Muhle, J.; Harth, C.M.; Izbicki, J.A.; Hilton, David R.; Weiss, R.F.

    2008-01-01

    Dissolved tetrafluoromethane (CF4) and sulfur hexafluoride (SF6) concentrations were measured in groundwater samples from the Eastern Morongo Basin (EMB) and Mojave River Basin (MRB) located in the southern Mojave Desert, California. Both CF4 and SF6 are supersaturated with respect to equilibrium with the preindustrial atmosphere at the recharge temperatures and elevations of the Mojave Desert. These observations provide the first in situ evidence for a flux of CF4 from the lithosphere. A gradual basin-wide enhancement in dissolved CF4 and SF6 concentrations with groundwater age is consistent with release of these gases during weathering of the surrounding granitic alluvium. Dissolved CF4 and SF6 concentrations in these groundwaters also contain a deeper crustal component associated with a lithospheric flux entering the EMB and MRB through the underlying basement. The crustal flux of CF4, but not of SF6, is enhanced in the vicinity of local active fault systems due to release of crustal fluids during episodic fracture events driven by local tectonic activity. When fluxes of CF4 and SF6 into Mojave Desert groundwaters are extrapolated to the global scale they are consistent, within large uncertainties, with the fluxes required to sustain the preindustrial atmospheric abundances of CF4 and SF6. ?? 2007 Elsevier Ltd. All rights reserved.

  11. Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.

    PubMed

    Li, Shengxiu; Sun, Guoqiang; Murai, Kiyohito; Ye, Peng; Shi, Yanhong

    2012-01-01

    TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression. Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells.

  12. Walking stability during cell phone use in healthy adults.

    PubMed

    Kao, Pei-Chun; Higginson, Christopher I; Seymour, Kelly; Kamerdze, Morgan; Higginson, Jill S

    2015-05-01

    The number of falls and/or accidental injuries associated with cellular phone use during walking is growing rapidly. Understanding the effects of concurrent cell phone use on human gait may help develop safety guidelines for pedestrians. It was shown previously that older adults had more pronounced dual-task interferences than younger adults when concurrent cognitive task required visual information processing. Thus, cell phone use might have greater impact on walking stability in older than in younger adults. This study examined gait stability and variability during a cell phone dialing task (phone) and two classic cognitive tasks, the Paced Auditory Serial Addition Test (PASAT) and Symbol Digit Modalities Test (SDMT). Nine older and seven younger healthy adults walked on a treadmill at four different conditions: walking only, PASAT, phone, and SDMT. We computed short-term local divergence exponent (LDE) of the trunk motion (local stability), dynamic margins of stability (MOS), step spatiotemporal measures, and kinematic variability. Older and younger adults had similar values of short-term LDE during all conditions, indicating that local stability was not affected by the dual-task. Compared to walking only, older and younger adults walked with significantly greater average mediolateral MOS during phone and SDMT conditions but significantly less ankle angle variability during all dual-tasks and less knee angle variability during PASAT. The current findings demonstrate that healthy adults may try to control foot placement and joint kinematics during cell phone use or another cognitive task with a visual component to ensure sufficient dynamic margins of stability and maintain local stability. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Joint morphogenetic cells in the adult mammalian synovium

    PubMed Central

    Roelofs, Anke J.; Zupan, Janja; Riemen, Anna H. K.; Kania, Karolina; Ansboro, Sharon; White, Nathan; Clark, Susan M.; De Bari, Cosimo

    2017-01-01

    The stem cells that safeguard synovial joints in adulthood are undefined. Studies on mesenchymal stromal/stem cells (MSCs) have mainly focused on bone marrow. Here we show that lineage tracing of Gdf5-expressing joint interzone cells identifies in adult mouse synovium an MSC population largely negative for the skeletal stem cell markers Nestin-GFP, Leptin receptor and Gremlin1. Following cartilage injury, Gdf5-lineage cells underpin synovial hyperplasia through proliferation, are recruited to a Nestin-GFPhigh perivascular population, and contribute to cartilage repair. The transcriptional co-factor Yap is upregulated after injury, and its conditional ablation in Gdf5-lineage cells prevents synovial lining hyperplasia and decreases contribution of Gdf5-lineage cells to cartilage repair. Cultured Gdf5-lineage cells exhibit progenitor activity for stable chondrocytes and are able to self-organize three-dimensionally to form a synovial lining-like layer. Finally, human synovial MSCs transduced with Bmp7 display morphogenetic properties by patterning a joint-like organ in vivo. Our findings further the understanding of the skeletal stem/progenitor cells in adult life. PMID:28508891

  14. Study of the 249-251Cf + 48Ca reactions: recent results and outlook

    NASA Astrophysics Data System (ADS)

    Voinov, A. A.; Oganessian, Yu Ts; Abdullin, F. Sh; Brewer, N. T.; Dmitriev, S. N.; Grzywacz, R. K.; Hamilton, J. H.; Itkis, M. G.; Miernik, K.; Polyakov, A. N.; Roberto, J. B.; Rykaczewski, K. P.; Sabelnikov, A. V.; Sagaidak, R. N.; Shirokovsky, I. V.; Shumeiko, M. V.; Stoyer, M. A.; Subbotin, V. G.; Sukhov, A. M.; Tsyganov, Yu S.; Utyonkov, V. K.; Vostokin, G. K.

    2018-02-01

    Experiment aiming at the synthesis of heavy isotopes of Z=118 (Og) using beam of 48Ca and a target of 249-251Cf was undertaken in October 2015 - April 2016 employing the Dubna Gas-Filled Recoil Separator (FLNR JINR). The target of mixed isotopes of 249-251Cf (50.7% of 249Cf, 12.9% of 250Cf, and 36.4% of 251Cf) was irradiated by 48Ca ions at two beam energies of 252 and 258 MeV with the corresponding accumulated beam doses of 1.6×1019 and 1.1×1019. A single event observed at lower beam energy was assigned to the isotope 294Og, the product of the reaction 249Cf(48Ca, 3n); its decay pattern and the observed radioactive properties of the nuclides in the decay chain reproduce in full those observed for 294Og in our earlier experiments of 2002-2005 and 2012. At higher beam energy we observed no decay chains that could be attributed to the isotopes of Og. The possibility of renewal of this experiment in the future is discussed.

  15. Pathogenesis and treatment of adult-type granulosa cell tumor of the ovary.

    PubMed

    Färkkilä, Anniina; Haltia, Ulla-Maija; Tapper, Johanna; McConechy, Melissa K; Huntsman, David G; Heikinheimo, Markku

    2017-08-01

    Adult-type granulosa cell tumor is a clinically and molecularly unique subtype of ovarian cancer. These tumors originate from the sex cord stromal cells of the ovary and represent 3-5% of all ovarian cancers. The majority of adult-type granulosa cell tumors are diagnosed at an early stage with an indolent prognosis. Surgery is the cornerstone for the treatment of both primary and relapsed tumor, while chemotherapy is applied only for advanced or non-resectable cases. Tumor stage is the only factor consistently associated with prognosis. However, every third of the patients relapse, typically in 4-7 years from diagnosis, leading to death in 50% of these patients. Anti-Müllerian Hormone and inhibin B are currently the most accurate circulating biomarkers. Adult-type granulosa cell tumors are molecularly characterized by a pathognomonic somatic missense point mutation 402C->G (C134W) in the transcription factor FOXL2. The FOXL2 402C->G mutation leads to increased proliferation and survival of granulosa cells, and promotes hormonal changes. Histological diagnosis of adult-type granulosa cell tumor is challenging, therefore testing for the FOXL2 mutation is crucial for differential diagnosis. Large international collaborations utilizing molecularly defined cohorts are essential to improve and validate new treatment strategies for patients with high-risk or relapsed adult-type granulosa cell tumor. Key Messages: Adult-type granulosa cell tumor is a unique ovarian cancer with an indolent, albeit unpredictable disease course. Adult-type granulosa cell tumors harbor a pathognomonic somatic missense mutation in transcription factor FOXL2. The key challenges in the treatment of patients with adult-type granulosa cell tumor lie in the identification and management of patients with high-risk or relapsed disease.

  16. Adult mesenchymal stem cells and cell-based tissue engineering

    PubMed Central

    Tuan, Rocky S; Boland, Genevieve; Tuli, Richard

    2003-01-01

    The identification of multipotential mesenchymal stem cells (MSCs) derived from adult human tissues, including bone marrow stroma and a number of connective tissues, has provided exciting prospects for cell-based tissue engineering and regeneration. This review focuses on the biology of MSCs, including their differentiation potentials in vitro and in vivo, and the application of MSCs in tissue engineering. Our current understanding of MSCs lags behind that of other stem cell types, such as hematopoietic stem cells. Future research should aim to define the cellular and molecular fingerprints of MSCs and elucidate their endogenous role(s) in normal and abnormal tissue functions. PMID:12716446

  17. Critical illness among adults with cystic fibrosis in Texas, 2004-2013: Patterns of ICU utilization, characteristics, and outcomes.

    PubMed

    Oud, Lavi

    2017-01-01

    Available reports on critically ill adults with cystic fibrosis (CF) suggest improving short-term outcomes. However, there is marked heterogeneity in reported findings, with studies mostly based on single-centered data, limiting generalizability. We sought to examine population-level patterns of demand for critical care resources, and the characteristics, resource utilization, and outcomes of ICU-managed adults with CF. We used the Texas Inpatient Public Use Data File to identify ICU admissions with CF aged ≥18 years in Texas between 2004-2013. We examined ICU utilization at population level (using CF Foundation annual reports) and, among ICU admissions, socio-demographic characteristics, burden of comorbidities, organ failure, life-support utilization and hospital disposition. Linear regression and multilevel logistic regression were used to examine temporal trends and predictors of short-term mortality (hospital death and discharge to hospice), respectively. Of 9,579 hospitalizations of adults with CF, 1,249 (13%) were admitted to ICU. The incidence of ICU admission among adults with CF in Texas increased between 2004-2005 and 2012-2013 from 16.7 to 19.2 per 100 person-years (p = 0.0181), with ICU admissions aged ≥30 years accounting for 80.3% of the change. Among ICU admissions the following changes were noted between 2004-2005 and 2012-2013: any organ failure 30.2% vs. 56.3% (p = 0.0004), mechanical ventilation 11.5% vs. 19.2% (p = 0.0216), and hemodialysis 1.0% vs. 8.1% (p = 0.0007). Short-term mortality for the whole cohort and for those with mechanical ventilation was 11.4% and 41.8%, respectively, with corresponding home discharge among survivors 84% and 62.1%, respectively. Key predictors (adjusted odds ratios [aOR (95% CI)]) of short-term mortality included age ≥45 years (2.051 [1.231-3.415]), female gender (1.907 [1.237-2.941]), and mechanical ventilation (7.982 [5.001-12.739]). Adults with CF had high and rising population-level burden of critical

  18. Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease.

    PubMed

    Ayoub, Fares; Trillo-Alvarez, Cesar; Morelli, Giuseppe; Lascano, Jorge

    2018-01-27

    To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis (CF) patients with hepatic steatosis as compared to normal CF controls. We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging (ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls. Data was collected on 114 patients meeting inclusion criteria. Seventeen patients (14.9%) were found to have hepatic steatosis on imaging. Being overweight (BMI > 25) ( P = 0.019) and having a higher ppFEV1 (75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level (27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes. Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher ppFEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis.

  19. Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease

    PubMed Central

    Ayoub, Fares; Trillo-Alvarez, Cesar; Morelli, Giuseppe; Lascano, Jorge

    2018-01-01

    AIM To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis (CF) patients with hepatic steatosis as compared to normal CF controls. METHODS We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging (ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls. RESULTS Data was collected on 114 patients meeting inclusion criteria. Seventeen patients (14.9%) were found to have hepatic steatosis on imaging. Being overweight (BMI > 25) (P = 0.019) and having a higher ppFEV1 (75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level (27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes. CONCLUSION Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher ppFEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis. PMID:29399276

  20. Product toxicity and cometabolic competitive inhibition modeling of chloroform and trichloroethylene transformation by methanotrophic resting cells.

    PubMed Central

    Alvarez-Cohen, L; McCarty, P L

    1991-01-01

    The rate and capacity for chloroform (CF) and trichloroethylene (TCE) transformation by a mixed methanotrophic culture of resting cells (no exogenous energy source) and formate-fed cells were measured. As reported previously for TCE, formate addition resulted in an increased CF transformation rate (0.35 day-1 for resting cells and 1.5 day-1 for formate-fed cells) and transformation capacity (0.0065 mg of CF per mg of cells for resting cells and 0.015 mg of CF per mg of cells for formate-fed cells), suggesting that depletion of energy stores affects transformation behavior. The observed finite transformation capacity, even with an exogenous energy source, suggests that toxicity was also a factor. CF transformation capacity was significantly lower than that for TCE, suggesting a greater toxicity from CF transformation. The toxicity of CF, TCE, and their transformation products to whole cells was evaluated by comparing the formate oxidation activity of acetylene-treated cells to that of non-acetylene-treated cells with and without prior exposure to CF or TCE. Acetylene arrests the activity of methane monooxygenase in CF and TCE oxidation without halting cell activity toward formate. Significantly diminished formate oxidation by cells exposed to either CR or TCE without acetylene compared with that with acetylene suggests that the solvents themselves were not toxic under the experimental conditions but their transformation products were. The concurrent transformation of CF and TCE by resting cells was measured, and results were compared with predictions from a competitive-inhibition cometabolic transformation model. The reasonable fit between model predictions and experimental observations was supportive of model assumptions. PMID:1905516

  1. Lubiprostone for constipation in adults with cystic fibrosis: a pilot study.

    PubMed

    O'Brien, Catherine E; Anderson, Paula J; Stowe, Cindy D

    2011-09-01

    Constipation is prevalent in the cystic fibrosis (CF) population and yet there are few data demonstrating the effectiveness of currently used treatments. Lubiprostone is a laxative that works by activating the type 2 chloride channel in the gastrointestinal tract and thus has the potential to be especially effective for constipation associated with CF. To evaluate the effectiveness of lubiprostone for the treatment of constipation in adults with CF. In this pilot study, participants acted as their own controls and comparisons were made between run-in and treatment periods. During the 2-week run-in period, participants continued their usual treatment for constipation; during the 4-week treatment period, participants received lubiprostone 24 μg twice daily. Efficacy outcomes included spontaneous bowel movement frequency, Bristol Stool Scale scores, and Patient Assessment of Constipation Symptoms (PAC-SYM) survey scores. Outcomes were assessed during both the run-in and treatment periods (0, 2, and 4 weeks of treatment). Safety outcomes included spirometry, body weight, and serum chemistry. Seven participants completed the study. Mean (SD) baseline forced expiratory volume in 1 second was 83.0% (9.4) of predicted and body mass index was 24.0 (2.8) kg/m², indicating an overall healthy, well-nourished group of adults with CF. Lubiprostone improved overall symptoms of constipation as measured by PAC-SYM survey scores (1.18 [0.56], 0.54 [0.27], and 0.44 [0.36] at 0, 2, and 4 weeks, respectively; p < 0.001). Spontaneous bowel movement frequency and Bristol Stool Scale scores were not statistically significantly different between periods. There were no differences in safety measures. Transient chest tightness and shortness of breath were reported by 2 separate participants, although neither participant withdrew due to these adverse effects. Lubiprostone may be an effective option for the treatment of constipation in adults with CF.

  2. Improved Cryptosporidium parvum oocysts propagation using dexamethasone suppressed CF-1 mice

    EPA Science Inventory

    This study evaluates Cryptosporidium parvum oocyst production in dexamethasone suppressed CF-1 and C57BL/6 mice. Both models can yield 1 x 109 total oocysts over a 20 day production period; however, only 20 CF-1 mice are required to reliably achieve this goal compared...

  3. Inflammation increases cells expressing ZSCAN4 and progenitor cell markers in the adult pancreas

    PubMed Central

    Azuma, Sakiko; Yokoyama, Yukihiro; Yamamoto, Akiko; Kyokane, Kazuhiro; Niida, Shumpei; Ishiguro, Hiroshi; Ko, Minoru S. H.

    2013-01-01

    We have recently identified the zinc finger and SCAN domain containing 4 (Zscan4), which is transiently expressed and regulates telomere elongation and genome stability in mouse embryonic stem (ES) cells. The aim of this study was to examine the expression of ZSCAN4 in the adult pancreas and elucidate the role of ZSCAN4 in tissue inflammation and subsequent regeneration. The expression of ZSCAN4 and other progenitor or differentiated cell markers in the human pancreas was immunohistochemically examined. Pancreas sections of alcoholic or autoimmune pancreatitis patients before and under maintenance corticosteroid treatment were used in this study. In the adult human pancreas a small number of ZSCAN4-positive (ZSCAN4+) cells are present among cells located in the islets of Langerhans, acini, ducts, and oval-shaped cells. These cells not only express differentiated cell markers for each compartment of the pancreas but also express other tissue stem/progenitor cell markers. Furthermore, the number of ZSCAN4+ cells dramatically increased in patients with chronic pancreatitis, especially in the pancreatic tissues of autoimmune pancreatitis actively regenerating under corticosteroid treatment. Interestingly, a number of ZSCAN4+ cells in the pancreas of autoimmune pancreatitis returned to the basal level after 1 yr of maintenance corticosteroid treatment. In conclusion, coexpression of progenitor cell markers and differentiated cell markers with ZSCAN4 in each compartment of the pancreas may indicate the presence of facultative progenitors for both exocrine and endocrine cells in the adult pancreas. PMID:23599043

  4. Cell Phone Use by Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Bryen, Diane Nelson; Carey, Allison; Friedman, Mark

    2007-01-01

    Although cell phone use has grown dramatically, there is a gap in cell phone access between people with disabilities and the general public. The importance of cell phone use among people with intellectual disabilities and studies about use of cell phones by adults with intellectual disabilities was described. Our goal was to determine the extent…

  5. Adult-type myogenesis of the frog Xenopus laevis specifically suppressed by notochord cells but promoted by spinal cord cells in vitro.

    PubMed

    Yamane, Hitomi; Ihara, Setsunosuke; Kuroda, Masaaki; Nishikawa, Akio

    2011-08-01

    Larval-to-adult myogenic conversion occurs in the dorsal muscle but not in the tail muscle during Xenopus laevis metamorphosis. To know the mechanism for tail-specific suppression of adult myogenesis, response character was compared between adult myogenic cells (Ad-cells) and larval tail myogenic cells (La-cells) to a Sonic hedgehog (Shh) inhibitor, notochord (Nc) cells, and spinal cord (SC) cells in vitro. Cyclopamine, an Shh inhibitor, suppressed the differentiation of cultured Ad (but not La) cells, suggesting the significance of Shh signaling in promoting adult myogenesis. To test the possibility that Shh-producing axial elements (notochord and spinal cord) regulate adult myogenesis, Ad-cells or La-cells were co-cultured with Nc or SC cells. The results showed that differentiation of Ad-cells were strongly inhibited by Nc cells but promoted by SC cells. If Ad-cells were "separately" co-cultured with Nc cells without direct cell-cell interactions, adult differentiation was not inhibited but rather promoted, suggesting that Nc cells have two roles, one is a short-range suppression and another is a long-range promotion for adult myogenesis. Immunohistochemical analysis showed both notochord and spinal cord express the N-terminal Shh fragment throughout metamorphosis. The "spinal cord-promotion" and long-range effect by Nc cells on adult myogenesis is thus involved in Shh signaling, while the signaling concerning the short-range "Nc suppression" will be determined by future studies. Interestingly, these effects, "Nc suppression" and "SC promotion" were not observed for La-cells. Situation where the spinal cord/notochord cross-sectional ratio is quite larger in tadpole trunk than in the tail seems to contribute to trunk-specific promotion and tail-specific suppression of adult myogenesis during Xenopus metamorphosis.

  6. Sleep quality and daytime function in adults with cystic fibrosis and severe lung disease.

    PubMed

    Dancey, D R; Tullis, E D; Heslegrave, R; Thornley, K; Hanly, P J

    2002-03-01

    It was hypothesized that adult cystic fibrosis (CF) patients with severe lung disease have impaired daytime function related to nocturnal hypoxaemia and sleep disruption. Nineteen CF patients (forced expiratory volume in one second 28+/-7% predicted) and 10 healthy subjects completed sleep diaries, overnight polysomnography (PSG), and assessment of daytime sleepiness and neurocognitive function. CF patients tended to report more awakenings (0.7+/-0.5 versus 0.3+/-0.2 x h(-1), p=0.08), and PSG revealed reduced sleep efficiency (71+/-25 versus 93+/-4%, p=0.004) and a higher frequency of awakenings (4.2+/-2.7 versus 2.4+/-1.4 x h(-1), p=0.06). Mean arterial oxygen saturation during sleep was lower in CF patients (84.4+/-6.8 versus 94.3+/-1.5%, p<0.0001) and was associated with reduced sleep efficiency (regression coefficient (r)=0.57, p=0.014). CF patients had short sleep latency on the multiple sleep latency test (6.7+/-3 min). The CF group reported lower levels of activation and happiness and greater levels of fatigue (p<0.01), which correlated with indices of sleep loss, such as sleep efficiency (r=0.47, p=10.05). Objective neurocognitive performance was also impaired in CF patients, reflected by lower throughput for simple addition/subtraction, serial reaction and colour-word conflict. The authors concluded that adult cystic fibrosis patients with severe lung disease have impaired neurocognitive function and daytime sleepiness, which is partly related to chronic sleep loss and nocturnal hypoxaemia.

  7. Axonal Control of the Adult Neural Stem Cell Niche

    PubMed Central

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D.; Tecott, Laurence H.; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-01-01

    SUMMARY The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSC) in the walls of the lateral ventricles of the adult brain. How the adult brain’s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

  8. Alkali metal and ammonium fluoro(trifluoroacetato)metallates M'[ M''3(μ3-F)(CF3COO)6(CF3COOH)3], where M' = Li, Na, K, NH4, Rb, or Cs and M'' = Ni or Co. Synthesis and crystal structures

    NASA Astrophysics Data System (ADS)

    Tereshchenko, D. S.; Morozov, I. V.; Boltalin, A. I.; Karpova, E. V.; Glazunova, T. Yu.; Troyanov, S. I.

    2013-01-01

    A series of fluoro(trifluoroacetato)metallates were synthesized by crystallization from solutions in trifluoroacetic acid containing nickel(II) or cobalt(II) nitrate hydrates and alkali metal or ammonium fluorides: Li[Ni3(μ3-F)(CF3COO)6(CF3COOH)3](CF3COOH)3 ( I), M'[Ni3(μ3-F)(CF3COO)6(CF3COOH)3] ( M' = Na ( II), NH4 ( IV), Rb ( V), and Cs ( VI)), NH4[Co3(μ3-F) (CF3COO)6(CF3COOH)3] ( III), and Cs[Ni3(μ3-F)(CF3COO)6(CF3COOH)3](CF3COOH)0.5 ( VII). The crystal structures of these compounds were determined by single-crystal X-ray diffraction. All structures contain triangular trinuclear complex anions [ M 3″(μ3-F)(CF3COO)6(CF3COOH)3]- ( M″ = Ni, Co) structurally similar to trinuclear 3d metal oxo carboxylate complexes. The three-coordinated F atom is located at the center of the triangle formed by Ni(II) or Co(II) atoms. The metal atoms are linked in pairs by six bridging trifluoroacetate groups located above and below the plane of the [ M″3 F] triangle. The oxygen atoms of the axial CF3COOH molecules complete the coordination environment of M″ atoms to an octahedron.

  9. Characterization of TLX Expression in Neural Stem Cells and Progenitor Cells in Adult Brains

    PubMed Central

    Li, Shengxiu; Sun, Guoqiang; Murai, Kiyohito; Ye, Peng; Shi, Yanhong

    2012-01-01

    TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression.Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells. PMID:22952666

  10. Neutral Gas Temperature Estimates in an Inductively Coupled CF4 Plasma by Fitting Diatomic Emission Spectra

    NASA Technical Reports Server (NTRS)

    Cruden, Brett A.; Rao, M. V. V. S.; Sharma, Surendra P.; Meyyappan, M.

    2001-01-01

    This work examines the accuracy of plasma neutral temperature estimates by fitting the rotational band envelope of different diatomic species in emission. Experiments are performed in an inductively coupled CF4 plasma generated in a Gaseous Electronics Conference reference cell. Visible and ultraviolet emission spectra are collected at a power of 300 W (approximately 0.7 W/cc) and pressure of 30 mtorr. The emission bands of several molecules (CF, CN, C2, CO, and SiF) are fit simultaneously for rotational and vibrational temperatures and compared. Four different rotational temperatures are obtained: 1250 K for CF and CN, 1600 K for CO, 1800 K for C2, and 2300 K for SiF. The vibrational temperatures obtained vary from 1750-5950 K, with the higher vibrational temperatures generally corresponding to the lower rotational temperatures. These results suggest that the different species have achieved different degrees of equilibration between the rotational and vibrational modes and may not be equilibrated with the translational temperatures. The different temperatures are also related to the likelihood that the species are produced by ion bombardment of the surface, with etch products like SiF, CO, and C2 having higher temperatures than species expected to have formed in the gas phase.

  11. Screening for ADHD in adults with cystic fibrosis: Prevalence, health-related quality of life, and adherence.

    PubMed

    Georgiopoulos, Anna M; Friedman, Deborah; Porter, Elizabeth A; Krasner, Amy; Kakarala, Sheetal P; Glaeser, Breanna K; Napoleon, Siena C; Wozniak, Janet

    2018-03-01

    International guidelines recommend depression and anxiety screening in individuals with cystic fibrosis (CF), but Attention-Deficit Hyperactivity Disorder (ADHD) remains understudied. Adults with CF (n=53) were screened using the Adult ADHD Self-Report Scale-v1.1 Symptom Checklist (ASRS-v1.1), Cystic Fibrosis Questionnaire-Revised (CFQ-R), and a self-report measure of treatment adherence. Elevated ADHD symptoms on the ASRS-v1.1 screener were reported by 15% of participants. Self-reported adherence, Body Mass Index in kg/m 2 (BMI), and Forced Expiratory Volume in 1 Second, Percent Predicted (FEV1%pred) did not differ between participants with vs. without elevated ADHD scores. Three CFQ-R scales, Physical Functioning, Role Functioning, and Respiratory Symptoms, were significantly lower in participants with elevated ADHD screens (unadjusted p<0.05). This difference remained statistically significant for the Role Functioning and Respiratory Symptoms scales following correction for multiple comparisons. The highly specific screening tool ASRS-v1.1 can ascertain previously undetected ADHD symptoms in adults with CF. ADHD was substantially more prevalent than expected in this population. Elevated ASRS-v1.1 screens correlated with poorer Health-Related Quality of Life (HRQoL) in some domains, but not with BMI, FEV1%pred, or self-reported CF treatment adherence. Additional research will elucidate the impact of ADHD and its treatment on HRQoL, CF self-care and health outcomes. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  12. Microstructural analysis of W-SiCf/SiC composite

    NASA Astrophysics Data System (ADS)

    Yoon, Hanki; Oh, Jeongseok; Kim, Gonho; Kim, Hyunsu; Takahashi, Heishichiro; Kohyama, Akira

    2015-03-01

    Continuous silicon carbide fiber-reinforced silicon carbide (SiCf/SiC) composites are promising structure candidates for future fusion power systems such as gas coolant fast channels, extreme high temperature reactor and fusion reactors, because of their intrinsic properties such as excellent mechanical properties, high thermal conductivity, good thermal-shock resistance as well as excellent physical and chemical stability in various environments under elevated temperature conditions. In this study, bonding of tungsten and SiCf/SiC was produced by hot-press method. Microstructure analyses were performed using SEM and TEM.

  13. Adult T-cell leukemia-associated antigen (ATLA): detection of a glycoprotein in cell- and virus-free supernatant.

    PubMed

    Yamamoto, N; Schneider, J; Hinuma, Y; Hunsmann, G

    1982-01-01

    A glycoprotein of an apparent molecular mass of 46,000, gp 46, was enriched by affinity chromatography from the virus- and cell-free culture medium of adult T-cell leukemia virus (ATLV) infected cells. gp 46 was specifically precipitated with sera from patients with adult T-cell leukemia associated antigen (ATLA). Thus, gp 46 is a novel component of the ATLA antigen complex.

  14. Mouse embryonic stem cell-derived cells reveal niches that support neuronal differentiation in the adult rat brain.

    PubMed

    Maya-Espinosa, Guadalupe; Collazo-Navarrete, Omar; Millán-Aldaco, Diana; Palomero-Rivero, Marcela; Guerrero-Flores, Gilda; Drucker-Colín, René; Covarrubias, Luis; Guerra-Crespo, Magdalena

    2015-02-01

    A neurogenic niche can be identified by the proliferation and differentiation of its naturally residing neural stem cells. However, it remains unclear whether "silent" neurogenic niches or regions suitable for neural differentiation, other than the areas of active neurogenesis, exist in the adult brain. Embryoid body (EB) cells derived from embryonic stem cells (ESCs) are endowed with a high potential to respond to specification and neuralization signals of the embryo. Hence, to identify microenvironments in the postnatal and adult rat brain with the capacity to support neuronal differentiation, we transplanted dissociated EB cells to conventional neurogenic and non-neurogenic regions. Our results show a neuronal differentiation pattern of EB cells that was dependent on the host region. Efficient neuronal differentiation of EB cells occurred within an adjacent region to the rostral migratory stream. EB cell differentiation was initially patchy and progressed toward an even distribution along the graft by 15-21 days post-transplantation, giving rise mostly to GABAergic neurons. EB cells in the striatum displayed a lower level of neuronal differentiation and derived into a significant number of astrocytes. Remarkably, when EB cells were transplanted to the striatum of adult rats after a local ischemic stroke, increased number of neuroblasts and neurons were observed. Unexpectedly, we determined that the adult substantia nigra pars compacta, considered a non-neurogenic area, harbors a robust neurogenic environment. Therefore, neurally uncommitted cells derived from ESCs can detect regions that support neuronal differentiation within the adult brain, a fundamental step for the development of stem cell-based replacement therapies. © 2014 AlphaMed Press.

  15. A new cytotoxic sterol methoxymethyl ether from a deep water marine sponge Scleritoderma sp. cf. paccardi.

    PubMed

    Gunasekera, S P; Kelly-Borges, M; Longley, R E

    1996-02-01

    24(R)-Methyl-5 alpha-cholest-7-enyl 3 beta-methoxymethyl ether (1), a new sterol ether, has been isolated from a deep-water marine sponge Scleritoderma sp. cf. paccardi. Compound 1 exhibited in vitro cytotoxicity against the cultured murine P-388 tumor cell line with an IC50 of 2.3 micrograms/mL. The isolation and structure elucidation of 1 by NMR spectroscopy is described.

  16. Tracheomalacia is associated with lower FEV1 and Pseudomonas acquisition in children with CF

    PubMed Central

    Fischer, Anthony J.; Singh, Sachinkumar B.; Adam, Ryan J.; Stoltz, David A.; Baranano, Christopher F.; Kao, Simon; Weinberger, Miles M.; McCray, Paul B.; Starner, Timothy D.

    2016-01-01

    BACKGROUND Tracheomalacia (TM) occurs in approximately 1 in 2,100 children. Because the trachea develops abnormally in animal models of cystic fibrosis (CF), we hypothesized this may also occur in children with CF, increasing their risk of TM. PURPOSE To examine the prevalence and clinical consequences of TM in children with CF. METHODS We studied children with CF born between 1995 and 2012. TM was defined as dynamic collapse of the trachea, and the severity was recorded as described in the chart. The effect of TM on patient outcomes, including FEV1, CT changes, and acquisition of CF pathogens, was assessed using a longitudinal patient dataset. RESULTS 89% of children with CF had at least one bronchoscopy (n = 97/109). 15% of these children had TM described in any bronchoscopy report (n= 15/97). Of the patients with TM, 8 had meconium ileus (p = 0.003) and all were pancreatic insufficient. Pseudomonas aeruginosa infection occurred 1.3 years earlier among children with TM (p = 0.01). Starting FEV1 values by age 8 were diminished by over 18% of predicted for patients with TM. Life-threatening episodes of airway obstruction occurred in 3 of 15 patients with CF and TM, including one leading to death. Gender, prematurity, and hepatic disease were not associated with TM. No difference was observed in the frequency of bronchiectasis. CONCLUSIONS TM is significantly more common in infants and children with CF than in the general population and is associated with airway obstruction and earlier Pseudomonas acquisition. PMID:24166775

  17. No evidence for β cell neogenesis in murine adult pancreas

    PubMed Central

    Xiao, Xiangwei; Chen, Zean; Shiota, Chiyo; Prasadan, Krishna; Guo, Ping; El-Gohary, Yousef; Paredes, Jose; Welsh, Carey; Wiersch, John; Gittes, George K.

    2013-01-01

    Whether facultative β cell progenitors exist in the adult pancreas is a major unsolved question. To date, lineage-tracing studies have provided conflicting results. To track β cell neogenesis in vivo, we generated transgenic mice that transiently coexpress mTomato and GFP in a time-sensitive, nonconditional Cre-mediated manner, so that insulin-producing cells express GFP under control of the insulin promoter, while all other cells express mTomato (INSCremTmG mice). Newly differentiated β cells were detected by flow cytometry and fluorescence microscopy, taking advantage of their transient coexpression of GFP and mTomato fluorescent proteins. We found that β cell neogenesis predominantly occurs during embryogenesis, decreases dramatically shortly after birth, and is completely absent in adults across various models of β cell loss, β cell growth and regeneration, and inflammation. Moreover, we demonstrated upregulation of neurogenin 3 (NGN3) in both proliferating ducts and preexisting β cells in the ligated pancreatic tail after pancreatic ductal ligation. These results are consistent with some recent reports, but argue against the widely held belief that NGN3 marks cells undergoing endocrine neogenesis in the pancreas. Our data suggest that β cell neogenesis in the adult pancreas occurs rarely, if ever, under either normal or pathological conditions. PMID:23619362

  18. [Management of acute and severe complications in adults with cystic fibrosis].

    PubMed

    Chapron, J; Zuber, B; Kanaan, R; Hubert, D; Desmazes-Dufeu, N; Mira, J-P; Dusser, D; Burgel, P-R

    2011-04-01

    The natural history of cystic fibrosis (CF) may be associated both with acute respiratory complications (respiratory exacerbations, haemoptysis, pneumothorax) and with non-respiratory complications (distal intestinal obstruction syndrome, dehydration) that may result in hospitalizations. The aim of this article is to describe the main therapeutic approaches that are adopted in the management of acute complications occurring in CF adults, and to discuss indications for admission of these patients to intensive care units. Adult CF patients admitted to intensive care unit often benefit from antibiotic courses adapted to their chronic bronchial infection, especially when the hospitalization is related to respiratory disease (including haemoptysis and pneumothorax). Nutritional support, including hypercaloric diet, control of hyperglycemia and pancreatic enzyme supplementation is warranted. The recommended therapy for major haemoptysis is bronchial artery embolization. Patient with significant pneumothorax should have a chest tube inserted, while the treatment of distal intestinal obstruction syndrome will most often be medical. In case of respiratory failure, non-invasive ventilation is the preferred mode of ventilatory support because invasive ventilation is associated with poor outcomes. Therapeutic options should always have been discussed between the patient, family members and the CF medical team to allow for informed decision making. Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  19. Survival of glucose phosphate isomerase null somatic cells and germ cells in adult mouse chimaeras

    PubMed Central

    Keighren, Margaret A.; Flockhart, Jean H.

    2016-01-01

    ABSTRACT The mouse Gpi1 gene encodes the glycolytic enzyme glucose phosphate isomerase. Homozygous Gpi1−/− null mouse embryos die but a previous study showed that some homozygous Gpi1−/− null cells survived when combined with wild-type cells in fetal chimaeras. One adult female Gpi1−/−↔Gpi1c/c chimaera with functional Gpi1−/− null oocytes was also identified in a preliminary study. The aims were to characterise the survival of Gpi1−/− null cells in adult Gpi1−/−↔Gpi1c/c chimaeras and determine if Gpi1−/− null germ cells are functional. Analysis of adult Gpi1−/−↔Gpi1c/c chimaeras with pigment and a reiterated transgenic lineage marker showed that low numbers of homozygous Gpi1−/− null cells could survive in many tissues of adult chimaeras, including oocytes. Breeding experiments confirmed that Gpi1−/− null oocytes in one female Gpi1−/−↔Gpi1c/c chimaera were functional and provided preliminary evidence that one male putative Gpi1−/−↔Gpi1c/c chimaera produced functional spermatozoa from homozygous Gpi1−/− null germ cells. Although the male chimaera was almost certainly Gpi1−/−↔Gpi1c/c, this part of the study is considered preliminary because only blood was typed for GPI. Gpi1−/− null germ cells should survive in a chimaeric testis if they are supported by wild-type Sertoli cells. It is also feasible that spermatozoa could bypass a block at GPI, but not blocks at some later steps in glycolysis, by using fructose, rather than glucose, as the substrate for glycolysis. Although chimaera analysis proved inefficient for studying the fate of Gpi1−/− null germ cells, it successfully identified functional Gpi1−/− null oocytes and revealed that some Gpi1−/− null cells could survive in many adult tissues. PMID:27103217

  20. Description and preliminary calibration results for the Langley hypersonic CF4 tunnel

    NASA Technical Reports Server (NTRS)

    Midden, R. E.; Miller, C. G.

    1978-01-01

    A detailed description of the hypersonic CF4 tunnel is presented along with discussion of the basic components, instrumentation, and operating procedure. Operational experience with the CF4 reclaimer and lead-bath heater is discussed. Comparison of measured and predicted shock detachment distance on a sphere and pressure distributions measured on a sharp leading-edge flat plate revealed the absence of significant flow nonuniformity and lent creditability to predicted free stream flow conditions. The economic operation of this facility centers about the CF4 reclaimer, which was designed to operate at an efficiency of 90 to 95 percent. A number of modifications were made to the reclaimer system to improve its performance, and presently, the system reclaims approximately 75 percent of the test gas. Even with current budgetary constraints, this efficiency permits the CF4 tunnel to be operated as a viable research wind tunnel.

  1. Testing Moderating Detection Systems with {sup 252}Cf-Based Reference Neutron Fields

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

    Hertel, Nolan E.; Sweezy, Jeremy; Sauber, Jeremiah S.

    Calibration measurements were carried out on a probe designed to measure ambient dose equivalent in accordance with ICRP Pub 60 recommendations. It consists of a cylindrical {sup 3}He proportional counter surrounded by a 25-cm-diameter spherical polyethylene moderator. Its neutron response is optimized for dose rate measurements of neutrons between thermal energies and 20 MeV. The instrument was used to measure the dose rate in four separate neutron fields: unmoderated {sup 252}Cf, D{sub 2}O-moderated {sup 252}Cf, polyethylene-moderated {sup 252}Cf, and WEP neutron howitzer with {sup 252}Cf at its center. Dose equivalent measurements were performed at source-detector centerline distances from 50 tomore » 200 cm. The ratio of air-scatter- and room-return-corrected ambient dose equivalent rates to ambient dose equivalent rates calculated with the code MCNP are tabulated.« less

  2. Bone Mineral Density and Fat-Soluble Vitamin Status in Adults with Cystic Fibrosis Undergoing Lung Transplantation: A Pilot Study.

    PubMed

    Hubert, Grace; Chung, Theresa Tam; Prosser, Connie; Lien, Dale; Weinkauf, Justin; Brown, Neil; Goodvin, Marianne; Jackson, Kathy; Tabak, Joan; Salgado, Josette; Alzaben, Abeer Salman; Mager, Diana R

    2016-12-01

    Patients with cystic fibrosis (CF) often experience low bone mineral density (BMD) pre- and post-lung transplantation (LTX). The study purpose was to describe BMD and micronutrient status in adults with CF pre- and post-LTX. Twelve patients with CF (29 ± 8 years) were recruited from the CF clinic at the University of Alberta Lung Transplant Program. BMD and vitamins A, D, E, K status, and parathyroid hormone were measured pre- and post-LTX. No significant differences pre- and post-LTX were observed at the different bone sites measured (lumber-spine, femoral-neck (FN), hip, and femoral-trochlea) (P > 0.05). BMD T-scores (<-2) was present in lumbar-spine, FN, hip, and femoral-trochlea in 33%, 17%, 17%, and 25% of individuals pre-LTX and 58%, 33%, 58%, and 33% of individuals post-LTX, respectively. More than 50% of patients had suboptimal vitamin K levels (PIVKA-II values >3 ng/mL) pre- and post-LTX. Adults with CF pre- and post-LTX had reduced BMD and suboptimal vitamin K status.

  3. Oxidative stress modulates the expression of genes involved in cell survival in ΔF508 cystic fibrosis airway epithelial cells.

    PubMed

    Voisin, Grégory; Bouvet, Guillaume F; Legendre, Pierre; Dagenais, André; Massé, Chantal; Berthiaume, Yves

    2014-09-01

    Although cystic fibrosis (CF) pathophysiology is explained by a defect in CF transmembrane conductance regulator (CFTR) protein, the broad spectrum of disease severity is the consequence of environmental and genetic factors. Among them, oxidative stress has been demonstrated to play an important role in the evolution of this disease, with susceptibility to oxidative damage, decline of pulmonary function, and impaired lung antioxidant defense. Although oxidative stress has been implicated in the regulation of inflammation, its molecular outcomes in CF cells remain to be evaluated. To address the question, we compared the gene expression profile in NuLi-1 cells with wild-type CFTR and CuFi-1 cells homozygous for ΔF508 mutation cultured at air-liquid interface. We analyzed the transcriptomic response of these cell lines with microarray technology, under basal culture conditions and after 24 h oxidative stress induced by 15 μM 2,3-dimethoxy-1,4-naphtoquinone. In the absence of oxidative conditions, CuFi-1 gene profiling showed typical dysregulated inflammatory responses compared with NuLi-1. In the presence of oxidative conditions, the transcriptome of CuFi-1 cells reflected apoptotic transcript modulation. These results were confirmed in the CFBE41o- and corrCFBE41o- cell lines as well as in primary culture of human CF airway epithelial cells. Altogether, our data point to the influence of oxidative stress on cell survival functions in CF and identify several genes that could be implicated in the inflammation response observed in CF patients. Copyright © 2014 the American Physiological Society.

  4. Genetics and epithelial cell dysfunction in cystic fibrosis

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

    Riordan, J.R.; Buchwald, M.

    1987-01-01

    This book examines the advances being made in the study of the physiology, cell biology, and molecular genetics of cystic fibrosis. Emphasis is placed on various areas of research that involve epithelial cells (e.g., the CF-specific phenotypes exhibited by epithelial cells, abnormalities in epithelium ion transport, chloride channel regulation in CF epithelial.) Coverage is presented on the current status of CF, including data on the incidence of the disease, its mode of inheritance, chromosomal localization, genetic heterogeneity, and screening and management.

  5. Derivation of Neural Stem Cells from Human Adult Peripheral CD34+ Cells for an Autologous Model of Neuroinflammation

    PubMed Central

    Wang, Tongguang; Choi, Elliot; Monaco, Maria Chiara G.; Campanac, Emilie; Medynets, Marie; Do, Thao; Rao, Prashant; Johnson, Kory R.; Elkahloun, Abdel G.; Von Geldern, Gloria; Johnson, Tory; Subramaniam, Sriram; Hoffman, Dax; Major, Eugene; Nath, Avindra

    2013-01-01

    Proinflammatory factors from activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox2, Oct3/4, c-Myc and Klf4. The derived NSC could be differentiated to glial cells and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine. PMID:24303066

  6. Creation and characterization of an airway epithelial cell line for stable expression of CFTR variants

    PubMed Central

    Gottschalk, Laura B.; Vecchio-Pagan, Briana; Sharma, Neeraj; Han, Sangwoo T.; Franca, Arianna; Wohler, Elizabeth S.; Batista, Denise A.S.; Goff, Loyal A.; Cutting, Garry R.

    2016-01-01

    Background Analysis of the functional consequences and treatment response of rare CFTR variants is challenging due to the limited availability of primary airways cells. Methods A Flp recombination target (FRT) site for stable expression of CFTR was incorporated into an immortalized CF bronchial epithelial cell line (CFBE41o−). CFTR cDNA was integrated into the FRT site. Expression was evaluated by western blotting and confocal microscopy and function measured by short circuit current. RNA sequencing was used to compare the transcriptional profile of the resulting CF8Flp cell line to primary cells and tissues. Results Functional CFTR was expressed from integrated cDNA at the FRT site of the CF8Flp cell line at levels comparable to that seen in native airway cells. CF8Flp cells expressing WT-CFTR have a stable transcriptome comparable to that of primary cultured airway epithelial cells, including genes that play key roles in CFTR pathways. Conclusion CF8Flp cells provide a viable substitute for primary CF airway cells for the analysis of CFTR variants in a native context. PMID:26694805

  7. Control of Cell Survival in Adult Mammalian Neurogenesis.

    PubMed

    Kuhn, H Georg

    2015-10-28

    The fact that continuous proliferation of stem cells and progenitors, as well as the production of new neurons, occurs in the adult mammalian central nervous system (CNS) raises several basic questions concerning the number of neurons required in a particular system. Can we observe continued growth of brain regions that sustain neurogenesis? Or does an elimination mechanism exist to maintain a constant number of cells? If so, are old neurons replaced, or are the new neurons competing for limited network access among each other? What signals support their survival and integration and what factors are responsible for their elimination? This review will address these and other questions regarding regulatory mechanisms that control cell-death and cell-survival mechanisms during neurogenesis in the intact adult mammalian brain. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  8. Highly preferential association of NonF508del CF mutations with the M470 allele.

    PubMed

    Ciminelli, B M; Bonizzato, A; Bombieri, C; Pompei, F; Gabaldo, M; Ciccacci, C; Begnini, A; Holubova, A; Zorzi, P; Piskackova, T; Macek, M; Castellani, C; Modiano, G; Pignatti, P F

    2007-01-01

    On the basis of previous findings on random individuals, we hypothesized a preferential association of CF causing mutations with the M allele of the M470V polymorphic site of the CFTR gene. We have determined the M/V-CF mutation haplotype in a series of 201 North East Italian and 73 Czech CF patients who were not F508del homozygotes, as F508del was already known to be fully associated with the M allele. Out of 358 not F508del CF genes, 84 carried the V allele and 274 the less common M allele. In the N-E Italian population, MM subjects have a risk of carrying a CF causing mutation 6.9x greater than VV subjects when F508del is excluded and 15.4x when F508del is included. In the Czech population a similar, although less pronounced, association is observed. Besides the possible biological significance of this association, the possibility of exploiting it for a pilot screening program has been explored in a local North East Italian population for which CF patients were characterized for their CF mutation. General M470V genotyping followed by common CF mutation screening limited to couples in which each partner carries at least one M allele would need testing only 39% of the couples, which contribute 89% of the total risk, with a cost benefit.

  9. Siglec-1 inhibits RSV-induced interferon gamma production by adultcells in contrast to newborn T cells.

    PubMed

    Jans, Jop; Unger, Wendy W J; Vissers, Marloes; Ahout, Inge M L; Schreurs, Inge; Wickenhagen, Arthur; de Groot, Ronald; de Jonge, Marien I; Ferwerda, Gerben

    2018-04-01

    Interferon gamma (IFN-γ) plays an important role in the antiviral immune response during respiratory syncytial virus (RSV) infections. Monocytes and T cells are recruited to the site of RSV infection, but it is unclear whether cell-cell interactions between monocytes and T cells regulate IFN-γ production. In this study, micro-array data identified the upregulation of sialic acid-binding immunoglobulin-type lectin 1 (Siglec-1) in human RSV-infected infants. In vitro, RSV increased expression of Siglec-1 on healthy newborn and adult monocytes. RSV-induced Siglec-1 on monocytes inhibited IFN-γ production by adult CD4 + T cells. In contrast, IFN-γ production by RSV in newborns was not affected by Siglec-1. The ligand for Siglec-1, CD43, is highly expressed on adult CD4 + T cells compared to newborns. Our data show that Siglec-1 reduces IFN-γ release by adultcells possibly by binding to the highly expressed CD43. The Siglec-1-dependent inhibition of IFN-γ in adults and the low expression of CD43 on newborn T cells provides a better understanding of the immune response against RSV in early life and adulthood. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. A rapid method for the measurement of sulfur hexafluoride (SF6), trifluoromethyl sulfur pentafluoride (SF5CF3), and Halon 1211 (CF2ClBr) in hydrologic tracer studies

    USGS Publications Warehouse

    Busenberg, Eurybiades; Plummer, Niel

    2010-01-01

    A rapid headspace method for the simultaneous laboratory determination of intentionally introduced hydrologic tracers, sulfur hexafluoride (SF6), trifluoromethyl sulfur pentafluoride (SF5CF3), Halon 1211 (CF2ClBr), and other halocarbons in water and gases is described. The high sensitivity of the procedure allows for introduction of minimal tracer mass (a few grams) into hydrologic systems with a large dynamic range of analytical detection (dilutions to 1:108). Analysis times by gas chromatography with electron capture detector are less than 1 min for SF6; about 2 min for SF6 and SF5CF3; and 4 min for SF6, SF5CF3, and Halon 1211. Many samples can be rapidly collected, preserved in stoppered septum bottles, and analyzed at a later time in the laboratory. Examples are provided showing the effectiveness of the gas tracer test studies in varied hydrogeological settings.

  11. A rapid method for the measurement of sulfur hexafluoride (SF6), trifluoromethyl sulfur pentafluoride (SF5CF3), and Halon 1211 (CF2ClBr) in hydrologic tracer studies

    NASA Astrophysics Data System (ADS)

    Busenberg, Eurybiades; Plummer, L. Niel

    2010-11-01

    A rapid headspace method for the simultaneous laboratory determination of intentionally introduced hydrologic tracers, sulfur hexafluoride (SF6), trifluoromethyl sulfur pentafluoride (SF5CF3), Halon 1211 (CF2ClBr), and other halocarbons in water and gases is described. The high sensitivity of the procedure allows for introduction of minimal tracer mass (a few grams) into hydrologic systems with a large dynamic range of analytical detection (dilutions to 1:108). Analysis times by gas chromatography with electron capture detector are less than 1 min for SF6; about 2 min for SF6 and SF5CF3; and 4 min for SF6, SF5CF3, and Halon 1211. Many samples can be rapidly collected, preserved in stoppered septum bottles, and analyzed at a later time in the laboratory. Examples are provided showing the effectiveness of the gas tracer test studies in varied hydrogeological settings.

  12. Identification of Newly Committed Pancreatic Cells in the Adult Mouse Pancreas.

    PubMed

    Socorro, Mairobys; Criscimanna, Angela; Riva, Patricia; Tandon, Manuj; Prasadan, Krishna; Guo, Ping; Humar, Abhinav; Husain, Sohail Z; Leach, Steven D; Gittes, George K; Esni, Farzad

    2017-12-13

    Multipotent epithelial cells with high Aldehyde dehydrogenase activity have been previously reported to exist in the adult pancreas. However, whether they represent true progenitor cells remains controversial. In this study, we isolated and characterized cells with ALDH activity in the adult mouse or human pancreas during physiological conditions or injury. We found that cells with ALDH activity are abundant in the mouse pancreas during early postnatal growth, pregnancy, and in mouse models of pancreatitis and type 1 diabetes (T1D). Importantly, a similar population of cells is found abundantly in healthy children, or in patients with pancreatitis or T1D. We further demonstrate that cells with ALDH activity can commit to either endocrine or acinar lineages, and can be divided into four sub-populations based on CD90 and Ecadherin expression. Finally, our in vitro and in vivo studies show that the progeny of ALDH1 + /CD90 - /Ecad - cells residing in the adult mouse pancreas have the ability to initiate Pancreatic and duodenal homeobox (Pdx1) expression for the first time. In summary, we provide evidence for the existence of a sortable population of multipotent non-epithelial cells in the adult pancreas that can commit to the pancreatic lineage following proliferation and mesenchymal to epithelial transition (MET).

  13. Therapeutics from Adult Stem Cells and the Hype Curve.

    PubMed

    Maguire, Greg

    2016-05-12

    The Gartner curve for regenerative and stem cell therapeutics is currently climbing out of the "trough of disillusionment" and into the "slope of enlightenment". Understanding that the early years of stem cell therapy relied on the model of embryonic stem cells (ESCs), and then moved into a period of the overhype of induced pluripotent stem cells (iPSCs), instead of using the model of 40 years of success, i.e. adult stem cells used in bone marrow transplants, the field of stem cell therapy has languished for years, trying to move beyond the early and poorly understood success of bone marrow transplants. Recent studies in the lab and clinic show that adult stem cells of various types, and the molecules that they release, avoid the issues associated with ESCs and iPSCs and lead to better therapeutic outcomes and into the slope of enlightenment.

  14. Altered Regulation of Airway Epithelial Cell Chloride Channels in Cystic Fibrosis

    NASA Astrophysics Data System (ADS)

    Frizzell, Raymond A.; Rechkemmer, Gerhard; Shoemaker, Richard L.

    1986-08-01

    In many epithelial cells the chloride conductance of the apical membrane increases during the stimulation of electrolyte secretion. Single-channel recordings from human airway epithelial cells showed that β -adrenergic stimulation evoked apical membrane chloride channel activity, but this response was absent in cells from patients with cystic fibrosis (CF). However, when membrane patches were excised from CF cells into media containing sufficient free calcium (approximately 180 nanomolar), chloride channels were activated. The chloride channels of CF cells were similar to those of normal cells as judged by their current-voltage relations, ion selectivity, and kinetic behavior. These findings demonstrate the presence of chloride channels in the apical membranes of CF airway cells. Their regulation by calcium appears to be intact, but cyclic adenosine monophosphate (cAMP)-dependent control of their activity is defective.

  15. Live Imaging of Adult Neural Stem Cells in Rodents

    PubMed Central

    Ortega, Felipe; Costa, Marcos R.

    2016-01-01

    The generation of cells of the neural lineage within the brain is not restricted to early development. New neurons, oligodendrocytes, and astrocytes are produced in the adult brain throughout the entire murine life. However, despite the extensive research performed in the field of adult neurogenesis during the past years, fundamental questions regarding the cell biology of adult neural stem cells (aNSCs) remain to be uncovered. For instance, it is crucial to elucidate whether a single aNSC is capable of differentiating into all three different macroglial cell types in vivo or these distinct progenies constitute entirely separate lineages. Similarly, the cell cycle length, the time and mode of division (symmetric vs. asymmetric) that these cells undergo within their lineage progression are interesting questions under current investigation. In this sense, live imaging constitutes a valuable ally in the search of reliable answers to the previous questions. In spite of the current limitations of technology new approaches are being developed and outstanding amount of knowledge is being piled up providing interesting insights in the behavior of aNSCs. Here, we will review the state of the art of live imaging as well as the alternative models that currently offer new answers to critical questions. PMID:27013941

  16. Germline stem cells and neo-oogenesis in the adult human ovary.

    PubMed

    Liu, Yifei; Wu, Chao; Lyu, Qifeng; Yang, Dongzi; Albertini, David F; Keefe, David L; Liu, Lin

    2007-06-01

    It remains unclear whether neo-oogenesis occurs in postnatal ovaries of mammals, based on studies in mice. We thought to test whether adult human ovaries contain germline stem cells (GSCs) and undergo neo-oogenesis. Rather than using genetic manipulation which is unethical in humans, we took the approach of analyzing the expression of meiotic marker genes and genes for germ cell proliferation, which are required for neo-oogenesis, in adult human ovaries covering an age range from 28 to 53 years old, compared to testis and fetal ovaries served as positive controls. We show that active meiosis, neo-oogenesis and GSCs are unlikely to exist in normal, adult, human ovaries. No early meiotic-specific or oogenesis-associated mRNAs for SPO11, PRDM9, SCP1, TERT and NOBOX were detectable in adult human ovaries using RT-PCR, compared to fetal ovary and adult testis controls. These findings are further corroborated by the absence of early meiocytes and proliferating germ cells in adult human ovarian cortex probed with markers for meiosis (SCP3), oogonium (OCT3/4, c-KIT), and cell cycle progression (Ki-67, PCNA), in contrast to fetal ovary controls. If postnatal oogenesis is confirmed in mice, then this species would represent an exception to the rule that neo-oogenesis does not occur in adults.

  17. The luminosity function for different morphological types in the CfA Redshift Survey

    NASA Technical Reports Server (NTRS)

    Marzke, Ronald O.; Geller, Margaret J.; Huchra, John P.; Corwin, Harold G., Jr.

    1994-01-01

    We derive the luminosity function for different morphological types in the original CfA Redshift Survey (CfA1) and in the first two slices of the CfA Redshift Survey Extension (CfA2). CfA1 is a complete sample containing 2397 galaxies distributed over 2.7 steradians with m(sub z) less than or equal 14.5. The first two complete slices of CfA2 contain 1862 galaxies distributed over 0.42 steradians with m(sub z)=15.5. The shapes of the E-S0 and spiral luminosity functions (LF) are indistinguishable. We do not confirm the steeply decreasing faint end in the E-S0 luminosity function found by Loveday et al. for an independent sample in the southern hemisphere. We demonstrate that incomplete classification in deep redshift surveys can lead to underestimates of the faint end of the elliptical luminosity function and could be partially responsible for the difference between the CfA survey and other local field surveys. The faint end of the LF for the Magellanic spirals and irregulars is very steep. The Sm-Im luminosity function is well fit by a Schechter function with M*=-18.79, alpha=-1.87, and phi*=0.6x10(exp -3) for M(sub z) less than or equal to -13. These galaxies are largely responsible for the excess at the faint end of the general CfA luminosity function. The abundance of intrinsically faint, blue galaxies nearby affects the interpretation of deep number counts. The dwarf population increases the expected counts at B=25 in a no-evolution, q(sub 0)=0.05 model by a factor of two over standard no-evolution estimates. These dwarfs change the expected median redshift in deep redshift surveys by less than 10 percent . Thus the steep Sm-Im LF may contribute to the reconciliation of deep number counts with deep redshift surveys.

  18. Pubertal Height Velocity and Associations with Pre-pubertal and Adult Heights in Cystic Fibrosis

    PubMed Central

    Zhang, Zhumin; Lindstrom, Mary J.; Lai, HuiChuan J.

    2013-01-01

    Objectives To test the hypothesis that pubertal peak height velocity (PHV) in cystic fibrosis (CF) has improved and is influenced by pre-pubertal growth and genetic potential. Study design PHV from 1862 children born in 1984–87 and documented in the 1986–2008 US CF Foundation Registry was determined by statistical modeling and classified into normal, delayed (2-SD > average age), attenuated (magnitude < 5th percentile), or both (D&A). Genetic potential for height was estimated by parental stature. Results PHV averaged 8.4 cm/y at age 14.0 y in boys and 7.0 cm/y at age 12.1 y in girls, ~6 mo delay and ~15% reduction compared with healthy children. PHV was normal in 60%, delayed in 9%, attenuated in 21% and D&A in 5%. Patients with delayed PHV reached similar adult height percentile (boys: 34th, girls: 46th) to those with normal PHV (boys: 33rd, girls: 34th); both were significantly taller than the attenuated (boys: 11th, girls: 19th) and D&A PHV subgroups (boys: 8th, girls: 14th). Pancreatic sufficient patients had taller pre-pubertal and adult heights but similar PHV compared with pancreatic insufficient or meconium ileus patients. Adjusting for genetic potential reduced adult height percentiles more in boys (25th to 16th) than girls (28th to 24th). Height at age 7 y, PHV age and magnitude, and parental stature significantly predicted adult height. Conclusions Pubertal PHV has improved in children with CF born after mid 1980s compared with older cohorts but remains below normal. Suboptimal pre-pubertal and pubertal growth led to adult height below genetic potential in CF. PMID:23535012

  19. Cell-free DNA characteristics and chimerism analysis in patients after allogeneic cell transplantation.

    PubMed

    Duque-Afonso, Jesus; Waterhouse, Miguel; Pfeifer, Dietmar; Follo, Marie; Duyster, Justus; Bertz, Hartmut; Finke, Jürgen

    2018-02-01

    Cell-free DNA (cfDNA) isolated from plasma or serum has received increasing interest for diagnostic applications in pregnancy, solid tumors and solid organ transplantation. The reported clinical usefulness of cfDNA obtained from plasma or serum in patients undergoing allogeneic cell transplantation (alloHSCT) is scarce. To analyze the potential clinical utility of cfDNA chimerism analysis after alloHSCT. A total of 196 samples obtained from 110 patients were investigated for their chimeric status both in peripheral blood and plasma using standard PCR for microsatellite amplification. Plasma DNA size distribution was analyzed using capillary electrophoresis. The mean cfDNA concentration in the transplanted patients was 469ng/ml (range: 50-10,700ng/ml). The size range of almost 80% of the analyzed fragments was between 80 and 200bp. In 41 out of the 110 patients included in the study a mixture of donor and recipient plasma cfDNA was detected. There was a statistically significant difference in the percentage of plasma mixed chimerism between the patients without transplant related complications and the patients with either GvHD (p<0.05) or relapse (p<0.01). In those patients who showed improvement of GvHD also displayed a decrease in the observable percentage of recipient cfDNA during GvHD treatment. In patients without improvement or even with worsening of acute GvHD, stable or increasing levels of recipient cfDNA were detected. cfDNA in combination with peripheral blood and bone marrow cell chimerism analysis might improve its utility in the clinic in particular in those patients with clinical complications after alloHSCT. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  20. Muscle Stem Cells: A Model System for Adult Stem Cell Biology.

    PubMed

    Cornelison, Ddw; Perdiguero, Eusebio

    2017-01-01

    Skeletal muscle stem cells, originally termed satellite cells for their position adjacent to differentiated muscle fibers, are absolutely required for the process of skeletal muscle repair and regeneration. In the last decade, satellite cells have become one of the most studied adult stem cell systems and have emerged as a standard model not only in the field of stem cell-driven tissue regeneration but also in stem cell dysfunction and aging. Here, we provide background in the field and discuss recent advances in our understanding of muscle stem cell function and dysfunction, particularly in the case of aging, and the potential involvement of muscle stem cells in genetic diseases such as the muscular dystrophies.

  1. Discovery and Synthesis of Caracolamide A, an Ion Channel Modulating Dichlorovinylidene Containing Phenethylamide from a Panamanian Marine Cyanobacterium cf. Symploca Species.

    PubMed

    Naman, C Benjamin; Almaliti, Jehad; Armstrong, Lorene; Caro-Díaz, Eduardo J; Pierce, Marsha L; Glukhov, Evgenia; Fenner, Amanda; Spadafora, Carmenza; Debonsi, Hosana M; Dorrestein, Pieter C; Murray, Thomas F; Gerwick, William H

    2017-08-25

    A recent untargeted metabolomics investigation into the chemical profile of 10 organic extracts from cf. Symploca spp. revealed several interesting chemical leads for further natural product drug discovery. Subsequent target-directed isolation efforts with one of these, a Panamanian marine cyanobacterium cf. Symploca sp., yielded a phenethylamide metabolite that terminates in a relatively rare gem-dichlorovinylidene moiety, caracolamide A (1), along with a known isotactic polymethoxy-1-alkene (2). Detailed NMR and HRESIMS analyses were used to determine the structures of these molecules, and compound 1 was confirmed by a three-step synthesis. Pure compound 1 was shown to have in vitro calcium influx and calcium channel oscillation modulatory activity when tested as low as 10 pM using cultured murine cortical neurons, but was not cytotoxic to NCI-H460 human non-small-cell lung cancer cells in vitro (IC 50 > 10 μM).

  2. Haloacyl complexes of boron, [(CF3)3BC(O)Hal]- (Hal=F, Cl, Br, I).

    PubMed

    Finze, Maik; Bernhardt, Eduard; Willner, Helge; Lehmann, Christian W

    2005-11-04

    The haloacyltris(trifluoromethyl)borate anions [(CF3)3BC(O)Hal]- (Hal=F, Cl, Br, I) have been synthesized by reacting (CF3)3BCO with either MHal (M=K, Cs; Hal=F) in SO2 or MHal (M=[nBu4N]+, [Et4N]+, [Ph4P]+; Hal=Cl, Br, I) in dichloromethane. Metathesis reactions of the fluoroacyl complex with Me3SiHal (Hal=Cl, Br, I) led to the formation of its higher homologues. The thermal stabilities of the haloacyltris(trifluoromethyl)borates decrease from the fluorine to the iodine derivative. The chemical reactivities decrease in the same order as demonstrated by a series of selected reactions. The new [(CF3)3BC(O)Hal]- (Hal=F, Cl, Br) salts are used as starting materials in the syntheses of novel compounds that contain the (CF3)3B-C fragment. All borate anions [(CF3)3BC(O)Hal]- (Hal=F, Cl, Br, I) have been characterized by multinuclear NMR spectroscopy (11B, 13C, 17O, 19F) and vibrational spectroscopy. [PPh4][(CF3)3BC(O)Br] crystallizes in the monoclinic space group P2/c (no. 13) and the bond parameters are compared with those of (CF3)3BCO and K[(CF3)3BC(O)F]. The interpretation of the spectroscopic and structural data are supported by DFT calculations [B3LYP/6-311+G(d)].

  3. Duration-sensitive neurons in the inferior colliculus of horseshoe bats: adaptations for using CF-FM echolocation pulses.

    PubMed

    Luo, Feng; Metzner, Walter; Wu, Feijian; Wu, Feijian J; Zhang, Shuyi; Zhang, Shuyi Y; Chen, Qicai; Chen, Qicai C

    2008-01-01

    The present study examines duration-sensitive neurons in the inferior colliculus (IC) of the least horseshoe bat, Rhinolophus pusillus, from China. In contrast to other bat species tested for duration selectivity so far, echolocation pulses emitted by horseshoe bats are generally longer and composed of a long constant-frequency (CF) component followed by a short downward frequency-modulated (FM) sweep (CF-FM pulse). We used combined CF-FM pulses to analyze the differential effects that these two pulse components had on the duration tuning in neurons of the horseshoe bat's IC. Consistent with results from other mammals, duration-sensitive neurons found in the least horseshoe bat fall into three main classes: short-pass, band-pass, and long-pass. Using a CF stimulus alone, 54% (51/95) of all IC neurons showed at least one form of duration selectivity at one or more stimulus intensities. In 65 of the 95 IC neurons tested with CF pulses, we were also able to test their duration selectivity for a combined CF-FM pulse, which increased the ratio of duration-sensitive neurons to 66% (43/65). Seven to 15 neurons that failed to show duration tuning for CF bursts became duration sensitive for CF-FM pulses, with most of them exhibiting short-pass (depending on stimulus intensity, between 4 and 8 neurons) or band-pass tuning (1-3 neurons). Increasing stimulus intensities did not affect the duration tuning in 53% (23/43) of duration-sensitive neurons for CF bursts and in about 26% (7/27) for CF-FM stimuli. In the remaining neurons, increasing sound levels generally reduced the ratio of duration-sensitive neurons to 33% for CF and 37% for CF-FM stimulation. In those that remained duration sensitive, louder CF bursts shortened best durations in band-pass neurons and cutoff durations in short- and long-pass neurons, whereas louder CF-FM stimuli reduced the cutoff durations only in short-pass neurons. Bandwidths of band-pass neurons were not significantly affected by any stimulus

  4. Mass-resolved ion energy measurements at both electrodes of a 13.56 MHz plasma in CF4

    NASA Astrophysics Data System (ADS)

    Snijkers, R. J. M. M.; van Sambeek, M. J. M.; Hoppenbrouwers, M. B.; Kroesen, G. M. W.; de Hoog, F. J.

    1996-06-01

    The ion energy distributions (IEDs) at the electrodes in a capacitively coupled 13.56 MHz plasma in CF4 have been measured mass resolved with a Balzers quadrupole in combination with a home-built energy analyzer. Mass-resolved determination offers the possibility to compare the IED of different ions achieved in the same sheath. The IEDs have been determined at both the largest and the smallest electrode. Apart from the IEDs of the CF4 species, the IEDs of ionic species in plasmas in argon and nitrogen also were determined. Apart from the CF4 ionic species CF+3, CF+2, CF+, and F+, CHF+2 ions also are present in the CF4 plasma due to residual water in the reactor. Because the CHF+2 ions are not produced in the sheath and because we do not detect elastically scattered ions, the IEDs of these ions show the typical bimodal distribution for rf plasmas which corresponds to an IED of ions which have not collided in the sheath. From these IEDs we can obtain the sheath characteristics, such as the averaged sheath potential. From the IEDs of CF+n ions one can conclude that, in the sheath of the CF4 plasma, a large number of chemical reactions takes place between the CF+n ions and the neutrals.

  5. Identification of tissue-specific cell death using methylation patterns of circulating DNA

    PubMed Central

    Lehmann-Werman, Roni; Neiman, Daniel; Zemmour, Hai; Moss, Joshua; Magenheim, Judith; Vaknin-Dembinsky, Adi; Rubertsson, Sten; Nellgård, Bengt; Blennow, Kaj; Zetterberg, Henrik; Spalding, Kirsty; Haller, Michael J.; Wasserfall, Clive H.; Schatz, Desmond A.; Greenbaum, Carla J.; Dorrell, Craig; Grompe, Markus; Zick, Aviad; Hubert, Ayala; Maoz, Myriam; Fendrich, Volker; Bartsch, Detlef K.; Golan, Talia; Ben Sasson, Shmuel A.; Zamir, Gideon; Razin, Aharon; Cedar, Howard; Shapiro, A. M. James; Glaser, Benjamin; Shemer, Ruth; Dor, Yuval

    2016-01-01

    Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DNA sequences in source tissues, so that cell death cannot be identified in tissues with a normal genome. We developed a method of detecting tissue-specific cell death in humans based on tissue-specific methylation patterns in cfDNA. We interrogated tissue-specific methylome databases to identify cell type-specific DNA methylation signatures and developed a method to detect these signatures in mixed DNA samples. We isolated cfDNA from plasma or serum of donors, treated the cfDNA with bisulfite, PCR-amplified the cfDNA, and sequenced it to quantify cfDNA carrying the methylation markers of the cell type of interest. Pancreatic β-cell DNA was identified in the circulation of patients with recently diagnosed type-1 diabetes and islet-graft recipients; oligodendrocyte DNA was identified in patients with relapsing multiple sclerosis; neuronal/glial DNA was identified in patients after traumatic brain injury or cardiac arrest; and exocrine pancreas DNA was identified in patients with pancreatic cancer or pancreatitis. This proof-of-concept study demonstrates that the tissue origins of cfDNA and thus the rate of death of specific cell types can be determined in humans. The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally invasive window for diagnosing and monitoring a broad spectrum of human pathologies as well as providing a better understanding of normal tissue dynamics. PMID:26976580

  6. A role for adult TLX-positive neural stem cells in learning and behaviour.

    PubMed

    Zhang, Chun-Li; Zou, Yuhua; He, Weimin; Gage, Fred H; Evans, Ronald M

    2008-02-21

    Neurogenesis persists in the adult brain and can be regulated by a plethora of external stimuli, such as learning, memory, exercise, environment and stress. Although newly generated neurons are able to migrate and preferentially incorporate into the neural network, how these cells are molecularly regulated and whether they are required for any normal brain function are unresolved questions. The adult neural stem cell pool is composed of orphan nuclear receptor TLX-positive cells. Here, using genetic approaches in mice, we demonstrate that TLX (also called NR2E1) regulates adult neural stem cell proliferation in a cell-autonomous manner by controlling a defined genetic network implicated in cell proliferation and growth. Consequently, specific removal of TLX from the adult mouse brain through inducible recombination results in a significant reduction of stem cell proliferation and a marked decrement in spatial learning. In contrast, the resulting suppression of adult neurogenesis does not affect contextual fear conditioning, locomotion or diurnal rhythmic activities, indicating a more selective contribution of newly generated neurons to specific cognitive functions.

  7. Sox10+ adult stem cells contribute to biomaterial encapsulation and microvascularization

    PubMed Central

    Wang, Dong; Wang, Aijun; Wu, Fan; Qiu, Xuefeng; Li, Ye; Chu, Julia; Huang, Wen-Chin; Xu, Kang; Gong, Xiaohua; Li, Song

    2017-01-01

    Implanted biomaterials and biomedical devices generally induce foreign body reaction and end up with encapsulation by a dense avascular fibrous layer enriched in extracellular matrix. Fibroblasts/myofibroblasts are thought to be the major cell type involved in encapsulation, but it is unclear whether and how stem cells contribute to this process. Here we show, for the first time, that Sox10+ adult stem cells contribute to both encapsulation and microvessel formation. Sox10+ adult stem cells were found sparsely in the stroma of subcutaneous loose connective tissues. Upon subcutaneous biomaterial implantation, Sox10+ stem cells were activated and recruited to the biomaterial scaffold, and differentiated into fibroblasts and then myofibroblasts. This differentiation process from Sox10+ stem cells to myofibroblasts could be recapitulated in vitro. On the other hand, Sox10+ stem cells could differentiate into perivascular cells to stabilize newly formed microvessels. Sox10+ stem cells and endothelial cells in three-dimensional co-culture self-assembled into microvessels, and platelet-derived growth factor had chemotactic effect on Sox10+ stem cells. Transplanted Sox10+ stem cells differentiated into smooth muscle cells to stabilize functional microvessels. These findings demonstrate the critical role of adult stem cells in tissue remodeling and unravel the complexity of stem cell fate determination. PMID:28071739

  8. Comparative Genome Analysis Provides Insights into Both the Lifestyle of Acidithiobacillus ferrivorans Strain CF27 and the Chimeric Nature of the Iron-Oxidizing Acidithiobacilli Genomes.

    PubMed

    Tran, Tam T T; Mangenot, Sophie; Magdelenat, Ghislaine; Payen, Emilie; Rouy, Zoé; Belahbib, Hassiba; Grail, Barry M; Johnson, D Barrie; Bonnefoy, Violaine; Talla, Emmanuel

    2017-01-01

    The iron-oxidizing species Acidithiobacillus ferrivorans is one of few acidophiles able to oxidize ferrous iron and reduced inorganic sulfur compounds at low temperatures (<10°C). To complete the genome of At. ferrivorans strain CF27, new sequences were generated, and an update assembly and functional annotation were undertaken, followed by a comparative analysis with other Acidithiobacillus species whose genomes are publically available. The At. ferrivorans CF27 genome comprises a 3,409,655 bp chromosome and a 46,453 bp plasmid. At. ferrivorans CF27 possesses genes allowing its adaptation to cold, metal(loid)-rich environments, as well as others that enable it to sense environmental changes, allowing At. ferrivorans CF27 to escape hostile conditions and to move toward favorable locations. Interestingly, the genome of At. ferrivorans CF27 exhibits a large number of genomic islands (mostly containing genes of unknown function), suggesting that a large number of genes has been acquired by horizontal gene transfer over time. Furthermore, several genes specific to At. ferrivorans CF27 have been identified that could be responsible for the phenotypic differences of this strain compared to other Acidithiobacillus species. Most genes located inside At. ferrivorans CF27-specific gene clusters which have been analyzed were expressed by both ferrous iron-grown and sulfur-attached cells, indicating that they are not pseudogenes and may play a role in both situations. Analysis of the taxonomic composition of genomes of the Acidithiobacillia infers that they are chimeric in nature, supporting the premise that they belong to a particular taxonomic class, distinct to other proteobacterial subgroups.

  9. Control of adult neurogenesis by programmed cell death in the mammalian brain.

    PubMed

    Ryu, Jae Ryun; Hong, Caroline Jeeyeon; Kim, Joo Yeon; Kim, Eun-Kyoung; Sun, Woong; Yu, Seong-Woon

    2016-04-21

    The presence of neural stem cells (NSCs) and the production of new neurons in the adult brain have received great attention from scientists and the public because of implications to brain plasticity and their potential use for treating currently incurable brain diseases. Adult neurogenesis is controlled at multiple levels, including proliferation, differentiation, migration, and programmed cell death (PCD). Among these, PCD is the last and most prominent process for regulating the final number of mature neurons integrated into neural circuits. PCD can be classified into apoptosis, necrosis, and autophagic cell death and emerging evidence suggests that all three may be important modes of cell death in neural stem/progenitor cells. However, the molecular mechanisms that regulate PCD and thereby impact the intricate balance between self-renewal, proliferation, and differentiation during adult neurogenesis are not well understood. In this comprehensive review, we focus on the extent, mechanism, and biological significance of PCD for the control of adult neurogenesis in the mammalian brain. The role of intrinsic and extrinsic factors in the regulation of PCD at the molecular and systems levels is also discussed. Adult neurogenesis is a dynamic process, and the signals for differentiation, proliferation, and death of neural progenitor/stem cells are closely interrelated. A better understanding of how adult neurogenesis is influenced by PCD will help lead to important insights relevant to brain health and diseases.

  10. Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis.

    PubMed

    Knudsen, K B; Pressler, T; Mortensen, L H; Jarden, M; Skov, M; Quittner, A L; Katzenstein, T; Boisen, K A

    2016-01-01

    Cystic fibrosis (CF) is a life shortening disease, however prognosis has improved and the adult population is growing. Most adults with cystic fibrosis live independent lives and balance the demands of work and family life with a significant treatment burden. The aim of this study was to examine the relationships among treatment adherence, symptoms of depression and health-related quality of life (HRQoL) in a population of young adults with CF. We administered three standardized questionnaires to 67 patients with CF aged 18-30 years; Morisky Medication Adherence Scale, Major Depression Inventory, and Cystic Fibrosis Questionnaire-Revised. There was a response rate of 77 % and a majority of the young adults (84 %) were employed or in an education program. Most participants (74 %) reported low adherence to medications. One third (32.8 %) of the participants reported symptoms of depression. HRQoL scores were especially low on Vitality and Treatment Burden, and symptoms of depression were associated with low HRQoL scores (p < 0.01) with medium to large deficits across on all HRQoL domains (Cohen's d 0.60-1.72) except for the domain treatment burden. High depression symptom scores were associated with low adherence (r = -0.412, p < 0.001). Despite improved physical health, many patients with CF report poor adherence, as well as impaired mental wellbeing and HRQoL. Thus, more attention to mental health issues is needed.

  11. Quality of life in children with CF: Psychometrics and relations with stress and mealtime behaviors.

    PubMed

    Driscoll, Kimberly A; Modi, Avani C; Filigno, Stephanie S; Brannon, Erin E; Chamberlin, Leigh Ann; Stark, Lori J; Powers, Scott W

    2015-06-01

    The purpose of this study was to evaluate the utility of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) with toddlers and preschool-aged children. Clinically relevant relations between health-related quality of life (HRQOL), stress, and mealtime behaviors have not been examined. It was hypothesized that problematic mealtime behaviors and increased stress would be negatively associated with HRQOL. Parents of 73 children (2-6 years) with CF completed questionnaires assessing their children's generic (PedsQL) and CF-specific HRQOL, parenting and CF-specific stress, and mealtime behaviors. CFQ-R Physical, Eating, and Respiratory HRQOL subscales had acceptable to strong reliability (alphas = 0.73-0.86); other scales approached acceptable reliability. Lower CF-specific stress was associated with higher CFQ-R Eating HRQOL (B = -0.84; P < 0.05) scores. Fewer eating problems were associated with higher CFQ-R Eating (B = -1.17; P < 0.0001) and Weight HRQOL (B = -0.78; P < 0.01) scores. As hypothesized, problematic eating and higher CF-specific stress was associated with lower CF-specific HRQOL. The CFQ-R has promise for use in young children with CF, but will need to be modified to exchange items not relevant to preschoolers with items that are more relevant to this age group. © 2014 Wiley Periodicals, Inc.

  12. Reactivity of CF(n) (n = 1-3) Radicals with a Silica Surface

    NASA Technical Reports Server (NTRS)

    Ricca, Alessandra

    1999-01-01

    The trends in reactivity of CF(n) radicals with SiO2 and the site selectivity of the attack are studied using two different cluster models. The reaction barriers for the most energetically favorable reaction are computed. It is shown that CF(n) radicals are fairly unreactive towards SiO2.

  13. A Rare Disease in Adult: Langerhans Cell Histiocytosis

    PubMed Central

    Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Koroglu, Mustafa; Kaya, Emin; Unlu, Serkan

    2013-01-01

    Langerhans cell histiocytosis is a rare histiocytic disorder and has been diagnosed in all age groups, but is most common in children. This disease is very rare in adults. We presented a patient who was 62 years old man diagnosed langerhans cell histiocytosis. PMID:29147350

  14. Dietary intake and nutritional status of micronutrients in adults with cystic fibrosis in relation to current recommendations.

    PubMed

    Li, Li; Somerset, Shawn

    2016-08-01

    An increased prevalence of cystic fibrosis (CF) related complications such as impaired bone health and diabetes has accompanied increased survival of patients with CF. This review was conducted to determine the extent to which adults with CF are meeting current nutrition recommendations for micronutrients in association with CF-related complications management. Although dietary intake and nutritional status in CF has improved significantly in recent decades, micronutrient status seems to have diverged. While vitamin A and E intakes appear adequate, frequent vitamin D and K deficiency/insufficiency and compromised bone health in CF, occurs despite supplementation. Although deficiency of water-soluble vitamins and minerals is uncommon, ongoing surveillance will enhance overall health outcomes, particularly in cases of CF-related liver disease and deteriorated lung function and bone health. Salt and fluid status in CF may also need attention due to diminished thirst sensation and voluntary rehydration. Further investigation in micronutrient status optimisation in CF will inform the development of more effective and targeted nutrition therapies to enable integration of more refined recommendations for micronutrient intakes in CF based on individual needs and disease progression. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  15. An Approach for Improvement of Carbon Fiber Technique to Study Cardiac Cell Contractility

    NASA Astrophysics Data System (ADS)

    Myachina, T.; Khokhlova, A.; Antsygin, I.; Lookin, O.

    2018-05-01

    The technologies to study cardiac cell mechanics in near-physiological conditions are limited. Carbon fiber (CF) technique is a unique tool to study single cardiomyocyte contractility. However, the CF adhesion to a cell is limited and it is difficult to control CF sliding occurred due to inappropriate adhesion. In this study, we present a CF adhesion quality index – a linear coefficient (slope) derived from “end-diastolic cell length - end-diastolic sarcomere length” relationship. Potential applicability of this index is demonstrated on isolated rat and guinea pig ventricular cardiomyocytes. Further improvement of the approach may help to increase the quality of the experimental data obtained by CF technique.

  16. Symposium 6: Young people, artificial nutrition and transitional care. The nutritional challenges of the young adult with cystic fibrosis: transition.

    PubMed

    Morton, Alison M

    2009-11-01

    Cystic fibrosis (CF) is a complex multisystem disorder affecting mainly the gastrointestinal tract and respiratory system. Intestinal malabsorption occurs in approximately 90% of patients. In the past, malnutrition was an inevitable consequence of disease progression, leading to poor growth, impaired respiratory muscle function, decreased exercise tolerance and immunological impairment. A positive association between body weight and height and survival has been widely reported. The energy requirements of patients with CF vary widely and generally increase with age and disease severity. For many young adults requirements will be 120-150% of the age-related estimated average requirement. To meet these energy needs patients are encouraged to eat a high-fat high-energy diet with appropriate pancreatic enzyme supplements. Many patients are unable to achieve an adequate intake as a result of a variety of factors including chronic poor appetite, infection-related anorexia, gastro-oesophageal reflux and abdominal pain. Oral energy supplements and enteral tube feeding are widely used. Nutritional support has been shown to improve nutritional status and stabilise or slow the rate of decline in lung function. With such emphasis on nutritional intake and nutritional status throughout life, poor adherence to therapies and issues relating to body image are emerging. The median survival of patients with CF is increasing. CF is now considered a life-limiting disease of adulthood rather than a terminal childhood illness. With increased longevity new challenges are emerging that include the transition of young adults with CF to adult services, CF-related diabetes, disordered eating, osteoporosis, liver disease and transplantation.

  17. Time-resolved detection of the CF3 photofragment using chirped QCL radiation.

    PubMed

    Hancock, G; Horrocks, S J; Ritchie, G A D; Helden, J H van; Walker, R J

    2008-10-09

    This paper demonstrates how a quantum cascade laser (QCL) in its intrapulse mode can provide a simple method for probing the products of a photolysis event. The system studied is the 266 nm photodissociation of CF3I with the CF3 fragments subsequently detected using radiation at approximately 1253 cm(-1) generated by a pulsed QCL. The tuning range provided by the frequency down-chirp of the QCL operated in its intrapulse mode allows a approximately 1 cm(-1) segment of the CF3 nu3 band to be measured following each photolysis laser pulse. Identification of features within this spectral region allows the CF3 ( v = 0) number density to be calculated as a function of pump-probe delay, and consequently the processes which populate and deplete this quantum state may be examined. Rate constants for the population cascade from higher vibrational levels into the v = 0 state, k 1, and for the recombination of the CF3 radicals to form C2F6, k2, are measured. The returned values of k1 = (2.3 +/- 0.34) x 10(-12) cm(3) molecule(-1) s(-1) and k2 = (3.9 +/- 0.34) x 10(-12) cm(3) molecule(-1) s(-1) are found to be in good agreement with reported literature values.

  18. Cobalamin Protection against Oxidative Stress in the Acidophilic Iron-oxidizing Bacterium Leptospirillum Group II CF-1

    PubMed Central

    Ferrer, Alonso; Rivera, Javier; Zapata, Claudia; Norambuena, Javiera; Sandoval, Álvaro; Chávez, Renato; Orellana, Omar; Levicán, Gloria

    2016-01-01

    Members of the genus Leptospirillum are aerobic iron-oxidizing bacteria belonging to the phylum Nitrospira. They are important members of microbial communities that catalyze the biomining of sulfidic ores, thereby solubilizing metal ions. These microorganisms live under extremely acidic and metal-loaded environments and thus must tolerate high concentrations of reactive oxygen species (ROS). Cobalamin (vitamin B12) is a cobalt-containing tetrapyrrole cofactor involved in intramolecular rearrangement reactions and has recently been suggested to be an intracellular antioxidant. In this work, we investigated the effect of the exogenous addition of cobalamin on oxidative stress parameters in Leptospirillum group II strain CF-1. Our results revealed that the external supplementation of cobalamin reduces the levels of intracellular ROSs and the damage to biomolecules, and also stimulates the growth and survival of cells exposed to oxidative stress exerted by ferric ion, hydrogen peroxide, chromate and diamide. Furthermore, exposure of strain CF-1 to oxidative stress elicitors resulted in the transcriptional activation of the cbiA gene encoding CbiA of the cobalamin biosynthetic pathway. Altogether, these data suggest that cobalamin plays an important role in redox protection of Leptospirillum strain CF-1, supporting survival of this microorganism under extremely oxidative environmental conditions. Understanding the mechanisms underlying the protective effect of cobalamin against oxidative stress may help to develop strategies to make biomining processes more effective. PMID:27242761

  19. Cobalamin Protection against Oxidative Stress in the Acidophilic Iron-oxidizing Bacterium Leptospirillum Group II CF-1.

    PubMed

    Ferrer, Alonso; Rivera, Javier; Zapata, Claudia; Norambuena, Javiera; Sandoval, Álvaro; Chávez, Renato; Orellana, Omar; Levicán, Gloria

    2016-01-01

    Members of the genus Leptospirillum are aerobic iron-oxidizing bacteria belonging to the phylum Nitrospira. They are important members of microbial communities that catalyze the biomining of sulfidic ores, thereby solubilizing metal ions. These microorganisms live under extremely acidic and metal-loaded environments and thus must tolerate high concentrations of reactive oxygen species (ROS). Cobalamin (vitamin B12) is a cobalt-containing tetrapyrrole cofactor involved in intramolecular rearrangement reactions and has recently been suggested to be an intracellular antioxidant. In this work, we investigated the effect of the exogenous addition of cobalamin on oxidative stress parameters in Leptospirillum group II strain CF-1. Our results revealed that the external supplementation of cobalamin reduces the levels of intracellular ROSs and the damage to biomolecules, and also stimulates the growth and survival of cells exposed to oxidative stress exerted by ferric ion, hydrogen peroxide, chromate and diamide. Furthermore, exposure of strain CF-1 to oxidative stress elicitors resulted in the transcriptional activation of the cbiA gene encoding CbiA of the cobalamin biosynthetic pathway. Altogether, these data suggest that cobalamin plays an important role in redox protection of Leptospirillum strain CF-1, supporting survival of this microorganism under extremely oxidative environmental conditions. Understanding the mechanisms underlying the protective effect of cobalamin against oxidative stress may help to develop strategies to make biomining processes more effective.

  20. Mast cell distribution in normal adult skin.

    PubMed

    Janssens, A S; Heide, R; den Hollander, J C; Mulder, P G M; Tank, B; Oranje, A P

    2005-03-01

    To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults. There was an uneven distribution of MCs in different body sites using the anti-tryptase monoclonal antibody technique. Numbers of MCs on the trunk, upper arm, and upper leg were similar, but were significantly different from those found on the lower leg and forearm. Two distinct groups were formed--proximal and distal. There were 77.0 MCs/mm2 at proximal body sites and 108.2 MCs/mm2 at distal sites. Adjusted for the adjacent diagnosis and age, this difference was consistent. The numbers of MCs in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders were not different from those in the control group. Differences in the numbers of MCs between the distal and the proximal body sites must be considered when MCs are counted for a reliable diagnosis of mastocytosis. A pilot study in patients with mastocytosis underlined the variation in the numbers of MCs in mastocytosis and normal skin, but showed a considerable overlap. The observed numbers of MCs in adults cannot be extrapolated to children. MC numbers varied significantly between proximal and distal body sites and these differences must be considered when MCs are counted for a reliable diagnosis of mastocytosis. There was a considerable overlap between the numbers of MCs in mastocytosis and normal skin.

  1. Associations between micronutrient intakes and gut microbiota in a group of adults with cystic fibrosis.

    PubMed

    Li, Li; Krause, Lutz; Somerset, Shawn

    2017-08-01

    Cystic fibrosis (CF) involves chronic inflammation and oxidative stress affecting mainly the respiratory and digestive systems. Survival rates for CF have improved with advances in treatment including nutritional interventions such as micronutrient supplementation. Diet can modulate gut microbiota in the general population with consequences on local and systemic immunity, and inflammation. The gut microbiota appears disrupted and may associate with pulmonary status in CF. This study investigated associations between micronutrient intakes and gut microbiota variations in a group of adults with CF. Faecal microbiota of sixteen free-living adults with CF was profiled by 16ss rDNA sequencing on the GS-FLX platform. Associations were tested between UniFrac distances of faecal microbiota and time-corresponding micronutrient intakes. Associations between relative abundances of bacterial taxa and micronutrient intakes (those showing significant associations with UniFrac distances) were examined by Spearman correlation. Unweighted UniFrac distances were associated with intakes of potassium and antioxidant vitamins C, E and beta-carotene equivalents, whereas weighted UniFrac distances were associated with antioxidant vitamins riboflavin, niacin equivalents, beta-carotene equivalents and vitamin A equivalents. Intakes of beta-carotene equivalents, vitamin C, vitamin E, niacin equivalents and riboflavin correlated negatively with Bacteroides and/or its corresponding higher level taxa. Intakes of beta-carotene equivalents and vitamin E also positively correlated with Firmicutes and specific taxa belonging to Firmicutes. Some micronutrients, particularly antioxidant vitamins, correlated with gut microbiota variations in the studied cohort. Further research is required to clarify whether antioxidant vitamin intakes can influence CF gut microbiota and potential clinical/therapeutic implications in CF. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and

  2. Cross-platform comparison for the detection of RAS mutations in cfDNA (ddPCR Biorad detection assay, BEAMing assay, and NGS strategy).

    PubMed

    Garcia, Jessica; Forestier, Julien; Dusserre, Eric; Wozny, Anne-Sophie; Geiguer, Florence; Merle, Patrick; Tissot, Claire; Ferraro-Peyret, Carole; Jones, Frederick S; Edelstein, Daniel L; Cheynet, Valérie; Bardel, Claire; Vilchez, Gaelle; Xu, Zhenyu; Bringuier, Pierre Paul; Barritault, Marc; Brengle-Pesce, Karen; Guillet, Marielle; Chauvenet, Marion; Manship, Brigitte; Brevet, Marie; Rodriguez-Lafrasse, Claire; Hervieu, Valérie; Couraud, Sébastien; Walter, Thomas; Payen, Léa

    2018-04-20

    CfDNA samples from colon (mCRC) and non-small cell lung cancers (NSCLC) (CIRCAN cohort) were compared using three platforms: droplet digital PCR (ddPCR, Biorad); BEAMing/OncoBEAM™-RAS-CRC (Sysmex Inostics); next-generation sequencing (NGS, Illumina), utilizing the 56G oncology panel (Swift Biosciences). Tissue biopsy and time matched cfDNA samples were collected at diagnosis in the mCRC cohort and during 1st progression in the NSCLC cohort. Excellent matches between cfDNA/FFPE mutation profiles were observed. Detection thresholds were between 0.5-1% for cfDNA samples examined using ddPCR and NGS, and 0.03% with BEAMing. This high level of sensitivity enabled the detection of KRAS mutations in 5/19 CRC patients with negative FFPE profiles. In the mCRC cohort, comparison of mutation results obtained by testing FFPE to those obtained by testing cfDNA by ddPCR resulted in 47% sensitivity, 77% specificity, 70% positive predictive value (PPV) and 55% negative predictive value (NPV). For BEAMing, we observed 93% sensitivity, 69% specificity, 78% PPV and 90% NPV. Finally, sensitivity of NGS was 73%, specificity was 77%, PPV 79% and NPV 71%. Our study highlights the complementarity of different diagnostic approaches and variability of results between OncoBEAM™-RAS-CRC and NGS assays. While the NGS assay provided a larger breadth of coverage of the major targetable alterations of 56 genes in one run, its performance for specific alterations was frequently confirmed by ddPCR results.

  3. Altered distribution of peripheral blood dendritic cell subsets in patients with pulmonary paracoccidioidomycosis.

    PubMed

    Venturini, James; Cavalcante, Ricardo Souza; Moris, Daniela Vanessa; Golim, Márjorie de Assis; Levorato, Adriele Dandara; Reis, Karoline Hagatha Dos; Arruda, Maria Sueli Parreira de; Mendes, Rinaldo Poncio

    2017-09-01

    Paracoccidioidomycosis (PCM) is a systemic mycosis caused by fungi from the genus Paracoccidioides in Latin America. PCM-patients (PCM-p) are classified as having acute/subacute or chronic (CF) clinical forms. CF is responsible for 75%-90% of all cases, affects mainly adults over 30 years old and the clinical manifestation are associated mainly with lungs and mucosa of upper airdigestive tract. In addition, the CF patients exhibit fibrosis of the lungs, oral mucous membranes and adrenals, and pulmonary emphysema. Consequently, CF PCM-p with active disease, as well as those that have been apparently cured, seem to be an interesting model for studies aiming to understand the long-term host-fungi relationship and hypoxia. Dendritic cells (DCs) constitute a system that serve as a major link between innate and adaptive immunity composed of several subpopulations of cells including two main subsets: myeloid (mDCs) and plasmacytoid (pDCs). The present study aimed to access the distribution of PBDC subsets of CF PCM-p who were not treated (NT) or treated (apparently cured - AC). CF PCM-p were categorized into two groups, consisting of 9 NTs and 9 ACs. Twenty-one healthy individuals were used as the control group. The determination of the PBDC subsets was performed by FACS (fluorescence-activated cell sorting) and the dosage of serum TNF-α, IL1β, IL-18, CCL3, IL-10 and basic fibroblast growth factor (bFGF) by ELISA (enzyme-linked immunosorbent assay). A high count and percentage of mDCs was observed before treatment, along with a low count of pDCs in treated patients. Furthermore, the mDC:pDC ratio and serum levels of TNF-α was higher in both of the PCM-p groups than in the control group. In conclusion, our findings demonstrated that active PCM influences the distribution of mDCs and pDCs, and after treatment, PCM-p retained a lower count of pDCs associated with pro-inflammatory profile. Therefore, we identified new evidences of persistent immunological abnormalities in

  4. Inhibitory effect of hot-water extract from dried fruit of Crataegus pinnatifida on low-density lipoprotein (LDL) oxidation in cell and cell-free systems.

    PubMed

    Chu, Chia-Yih; Lee, Miao-Jane; Liao, Chuen-Lan; Lin, Wea-Lung; Yin, Yu-Fang; Tseng, Tsui-Hwa

    2003-12-17

    The dried fruit of Crataegus pinnatifida, a local soft drink material and medical herb, was found to possess potential against oxidative stress. In the preliminary study, the antioxidant potential of a hot-water extract obtained from the dried fruit of C. pinnatifida (CF-H) was evaluated in terms of its capacity of quenching 1,1-diphenyl-2-picrylhydrazyl free radicals (EC(50) = 0.118 mg/mL). After content analysis, it was found that CF-H is mainly composed of polyphenols including flavonoids (6.9%), procyanidins (2.2%), (+)-catechin (0.5%), and (-)-epicatechin (0.2%). The antioxidative bioactivity of CF-H had been assess previously using the models of CuSO(4) as cell-free system and sodium nitroprusside (SNP) plus macrophage RAW 264.7 cells as cell system to induce human low-density lipoprotein oxidation. CF-H was found to inhibit relative electrophoretic mobility and thiobarbituric acid reactive substances at the concentration of 0.5-1.0 mg/mL in the cell-free system and at 0.01-0.10 mg/mL in the cell system. Furthermore, it was found that CF-H decreased the SNP-induced cell lipid peroxidation and reduced glutathione depletion.

  5. Intracavitary moderator balloon combined with (252)Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations.

    PubMed

    Brandão, S F; Campos, T P R

    2015-07-01

    This article proposes a combination of californium-252 ((252)Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Dosimetric evaluations were performed on three protocol set-ups: (252)Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0-5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the (252)Cf source, sparing the normal brain tissue. Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis.

  6. Atmospheric lifetime of SF5CF3

    NASA Astrophysics Data System (ADS)

    Takahashi, K.; Nakayama, T.; Matsumi, Y.; Solomon, S.; Gejo, T.; Shigemasa, E.; Wallington, T. J.

    2002-08-01

    The vacuum ultraviolet (VUV) absorption spectrum of SF5CF3 was measured over the range 106-200 nm. At 121.6 nm, σ(base e) = (7.8 +/- 0.6) × 10-18 cm2 molecule-1, in which quoted uncertainty includes two standard deviation from the least-square fit in the Beer-Lambert plot and our estimate of potential systematic errors associated with measurements of the reactant concentrations. The VUV spectrum and literature data for electron attachment and ion-molecule reactions were incorporated into a model of the stratosphere, mesosphere, and lower thermosphere. This information provides better constraints on the atmospheric lifetime and hence on the potential of this highly radiatively-active trace gas to influence the climate system. The atmospheric lifetime of SF5CF3 is dominated by dissociative electron attachment and is estimated to be approximately 950 years. Solar proton events could reduce this to a lower limit of 650 years.

  7. CF6 jet engine performance deterioration results

    NASA Technical Reports Server (NTRS)

    Lewis, R. J.; Humerickhouse, C. E.; Paas, J. E.

    1978-01-01

    The use of the performance baseline from the flight planning manual as a reference to measure changes in cruise fuel flow rates was discussed. For the CF6-6D engine, the introduction of design changes for performance and durability reasons was seen to introduce an average increment relative to this baseline of 3.2% WFM increase at Nl, 2.5% Fn increase at Nl, 0.8% specific fuel consumption (SFC) increase at Fn, and 7 C EGT increase at Nl, while maintaining sufficient SFC margin of the delivered airplane. The effect of revenue service deterioration and performance restoration relative to the reference was shown to be an adder on top of these design effects. A schematic of typical CF6-6D performance through revenue service and airline maintenance is presented in terms of percent cruise SFC relative to an airline datum point (average level upon entering revenue service). The typical changes in SFC margin are shown for airline revenue service through for installations and refurbishments.

  8. Human Dental Pulp Cells Differentiate toward Neuronal Cells and Promote Neuroregeneration in Adult Organotypic Hippocampal Slices In Vitro.

    PubMed

    Xiao, Li; Ide, Ryoji; Saiki, Chikako; Kumazawa, Yasuo; Okamura, Hisashi

    2017-08-11

    The adult mammalian central nerve system has fundamental difficulties regarding effective neuroregeneration. The aim of this study is to investigate whether human dental pulp cells (DPCs) can promote neuroregeneration by (i) being differentiated toward neuronal cells and/or (ii) stimulating local neurogenesis in the adult hippocampus. Using immunostaining, we demonstrated that adult human dental pulp contains multipotent DPCs, including STRO-1, CD146 and P75-positive stem cells. DPC-formed spheroids were able to differentiate into neuronal, vascular, osteogenic and cartilaginous lineages under osteogenic induction. However, under neuronal inductive conditions, cells in the DPC-formed spheroids differentiated toward neuronal rather than other lineages. Electrophysiological study showed that these cells consistently exhibit the capacity to produce action potentials, suggesting that they have a functional feature in neuronal cells. We further co-cultivated DPCs with adult mouse hippocampal slices on matrigel in vitro. Immunostaining and presto blue assay showed that DPCs were able to stimulate the growth of neuronal cells (especially neurons) in both the CA1 zone and the edges of the hippocampal slices. Brain-derived neurotrophic factor (BDNF), was expressed in co-cultivated DPCs. In conclusion, our data demonstrated that DPCs are well-suited to differentiate into the neuronal lineage. They are able to stimulate neurogenesis in the adult mouse hippocampus through neurotrophic support in vitro.

  9. Human Dental Pulp Cells Differentiate toward Neuronal Cells and Promote Neuroregeneration in Adult Organotypic Hippocampal Slices In Vitro

    PubMed Central

    Ide, Ryoji; Saiki, Chikako; Kumazawa, Yasuo; Okamura, Hisashi

    2017-01-01

    The adult mammalian central nerve system has fundamental difficulties regarding effective neuroregeneration. The aim of this study is to investigate whether human dental pulp cells (DPCs) can promote neuroregeneration by (i) being differentiated toward neuronal cells and/or (ii) stimulating local neurogenesis in the adult hippocampus. Using immunostaining, we demonstrated that adult human dental pulp contains multipotent DPCs, including STRO-1, CD146 and P75-positive stem cells. DPC-formed spheroids were able to differentiate into neuronal, vascular, osteogenic and cartilaginous lineages under osteogenic induction. However, under neuronal inductive conditions, cells in the DPC-formed spheroids differentiated toward neuronal rather than other lineages. Electrophysiological study showed that these cells consistently exhibit the capacity to produce action potentials, suggesting that they have a functional feature in neuronal cells. We further co-cultivated DPCs with adult mouse hippocampal slices on matrigel in vitro. Immunostaining and presto blue assay showed that DPCs were able to stimulate the growth of neuronal cells (especially neurons) in both the CA1 zone and the edges of the hippocampal slices. Brain-derived neurotrophic factor (BDNF), was expressed in co-cultivated DPCs. In conclusion, our data demonstrated that DPCs are well-suited to differentiate into the neuronal lineage. They are able to stimulate neurogenesis in the adult mouse hippocampus through neurotrophic support in vitro. PMID:28800076

  10. The effect of the weather on pulmonary exacerbations and viral infections among adults with cystic fibrosis.

    PubMed

    Flight, W G; Bright-Thomas, R J; Sarran, C; Mutton, K J; Morris, J; Webb, A K; Jones, A M

    2014-11-01

    The effect of changes in the weather on the respiratory health of patients with cystic fibrosis (CF) is unclear. We conducted a prospective study to determine the impact of climate and season on the incidence of viral respiratory infections (VRI) and pulmonary exacerbations (PEx) among adults with CF. Between December 2010 and April 2012, 98 adults with CF were followed for 12 months. Polymerase chain reaction assays for nine viruses were performed on sputum, nose and throat swabs every 2 months and additionally at onset of PEx. Hourly temperature and relative humidity measurements were recorded throughout the study. Statistical analysis utilized generalized estimating equation (GEE) models. Pre-specified criteria for VRI and PEx were met at 29% and 37% of visits, respectively. Rhinovirus accounted for 72% of identified viruses. Incidence of rhinovirus peaked in autumn while non-rhinovirus VRI peaked in winter. Rhinovirus was associated with increased mean temperatures (OR 1.07; p = 0.001), while non-rhinovirus VRI was associated with lower mean temperatures (OR 0.87; p < 0.001). PEx occurred frequently throughout the study with no clear seasonal pattern observed. There was no significant association between climate variables and the incidence of either PEx or antibiotic prescription. There is a seasonal pattern to VRI in adults with CF. The incidence of VRI but not PEx is associated with changes in ambient temperature.

  11. CF3 Derivatives of the Anticancer Ru(III) Complexes KP1019, NKP-1339, and Their Imidazole and Pyridine Analogues Show Enhanced Lipophilicity, Albumin Interactions, and Cytotoxicity.

    PubMed

    Chang, Stephanie W; Lewis, Andrew R; Prosser, Kathleen E; Thompson, John R; Gladkikh, Margarita; Bally, Marcel B; Warren, Jeffrey J; Walsby, Charles J

    2016-05-16

    The Ru(III) complexes indazolium [trans-RuCl4(1H-indazole)2] (KP1019) and sodium [trans-RuCl4(1H-indazole)2] (NKP-1339) are leading candidates for the next generation of metal-based chemotherapeutics. Trifluoromethyl derivatives of these compounds and their imidazole and pyridine analogues were synthesized to probe the effect of ligand lipophilicity on the pharmacological properties of these types of complexes. Addition of CF3 groups also provided a spectroscopic handle for (19)F NMR studies of ligand exchange processes and protein interactions. The lipophilicities of the CF3-functionalized compounds and their unsubstituted parent complexes were quantified by the shake-flask method to give the distribution coefficient D at pH 7.4 (log D7.4). The solution behavior of the CF3-functionalized complexes was characterized in phosphate-buffered saline (PBS) using (19)F NMR, electron paramagnetic resonance (EPR), and UV-vis spectroscopies. These techniques, along with fluorescence competition experiments, were also used to characterize interactions with human serum albumin (HSA). From these studies it was determined that increased lipophilicity correlates with reduced solubility in PBS but enhancement of noncoordinate interactions with hydrophobic domains of HSA. These protein interactions improve the solubility of the complexes and inhibit the formation of oligomeric species. EPR measurements also demonstrated the formation of HSA-coordinated species with longer incubation. (19)F NMR spectra show that the trifluoromethyl complexes release axial ligands in PBS and in the presence of HSA. In vitro testing showed that the most lipophilic complexes had the greatest cytotoxic activity. Addition of CF3 groups enhances the activity of the indazole complex against A549 nonsmall cell lung carcinoma cells. Furthermore, in the case of the pyridine complexes, the parent compound was inactive against the HT-29 human colon carcinoma cell line but showed strong cytotoxicity with CF3

  12. The reliability and concurrent validity of the Scoliosis Research Society-22r patient questionnaire compared with the Child Health Questionnaire-CF87 patient questionnaire for adolescent spinal deformity.

    PubMed

    Glattes, R Christopher; Burton, Douglas C; Lai, Sue Min; Frasier, Elizabeth; Asher, Marc A

    2007-07-15

    This is a clinic-based cross-sectional study involving 2 health-related quality-of-life (HRQL) questionnaires. To compare the score distribution and reliability of the spinal deformity specific Scoliosis Research Society-22r (SRS-22r) questionnaire and the established generic Child Health Questionnaire-CF87 (CHQ-CF87), and to assess the concurrent validity of the SRS-22r using the CHQ-CF87 in an adolescent spine deformity population. Different questionnaires are commonly thought to be necessary to assess the HRQL of adolescent and adult populations. But since spinal deformities usually begin in the second decade of life, longitudinal follow-up with the same HRQL is desirable. The SRS-22r HRQL has recently been validated for score distribution and internal consistency in a spinal deformity population ranging in age from 7 to 78 years. The SRS-22r and CHQ-CF87 HRQLs were completed by 70 orthopedic spinal deformity outpatients 8 to 18 years of age, of whom 54 returned mailed retest questionnaires at an average of 24 days later. The ceiling effect averaged 27% for the SRS-22r and 36% for the CHQ-CF87. Respective values for internal consistency (Cronbach alpha) were 0.81 and 0.82, and for test-retest reproducibility the intraclass correlations (ICC) were 0.73 and 0.61. Concurrent validity was r > or = 0.68 or more for relevant function, pain, and mental health domains. The SRS Self-Image and particularly the Satisfaction/Dissatisfaction with Management domains did not correlate well with any CHQ-CF87 domains (r = 0.50 and 0.30, respectively). In a spinal deformity population 8 to 18 years of age, the score distribution and reliability, internal consistency, and reproducibility of the SRS-22r were at least as good as the CHQ-CF87. The SRS-22r function, pain, and mental health domains were concurrently valid in comparison to relevant CHQ-CF87 domains, but the SRS-22r self-image and satisfaction/dissatisfaction domains were not, thereby providing health-related quality

  13. The Epigenetics of Adult (Somatic) Stem Cells

    PubMed Central

    Eilertsen, Kenneth J.; Floyd, Z. Elizabeth; Gimble, Jeffrey M.

    2009-01-01

    While genetic studies have provided a wealth of information about health and disease, there is a growing awareness that individual characteristics are also determined by factors other than genetic sequences. These “epigenetic” changes broadly encompass the influence of the environment on gene regulation and expression and in a more narrow sense, describe the mechanisms controlling DNA methylation, histone modification and genetic imprinting. In this review, we focus on the epigenetic mechanisms that regulate adult (somatic) stem cell differentiation, beginning with the metabolic pathways and factors regulating chromatin structure and DNA methylation and the molecular biological tools that are currently available to study these processes. The role of these epigenetic mechanisms in manipulating adult stem cells is followed by a discussion of the challenges and opportunities facing this emerging field. PMID:18540823

  14. Spirometry-related pain and distress in adolescents and young adults with cystic fibrosis: The role of acceptance

    PubMed Central

    Casier, Annabelle; Goubert, Liesbet; Vervoort, Tine; Theunis, Marleen; Huse, Danielle; De Baets, Frans; Matthys, Dirk; Crombez, Geert

    2013-01-01

    OBJECTIVE: To investigate the occurrence of spirometry-related pain and distress in adolescents and young adults with cystic fibrosis (CF), and to investigate the role of acceptance of illness in spirometry-related pain and distress. METHODS: A total of 36 adolescents and young adults with CF (12 to 22 years of age) completed a questionnaire assessing acceptance of illness. Spirometry-related distress was assessed using self-report (ie, anxiety/worry about the procedure) and physiological outcomes (ie, heart rate and heart rate variability) before spirometry. Spirometry-related pain was assessed using self-report (ie, expected pain and pain-related thoughts). Self-reported distress and pain during spirometry were also assessed. RESULTS: Eighty-nine per cent of subjects reported distress before spirometry, 67% experienced distress during spirometry, 28% expected pain during spirometry and 22% actually experienced pain. Interestingly, partial correlations revealed that more acceptance was related to less expected pain and pain-related thoughts. Acceptance, however, was unrelated to distress, anxiety and pain during spirometry. DISCUSSION: The present study suggests that a non-negligible number of adolescents and young adults with CF experience pain and distress during spirometry. Furthermore, results indicate that acceptance may play a protective role in the more indirect consequences of CF such as expected pain and pain-related thoughts during medical procedures. Acceptance, however, was not related to distress before and during spirometry, nor to experienced pain. These findings contribute to the increasing evidence that acceptance may play a protective role in managing the consequences of living with CF. PMID:23985580

  15. Core Facility of the Juelich Observatory for Cloud Evolution (JOYCE - CF)

    NASA Astrophysics Data System (ADS)

    Beer, J.; Troemel, S.

    2017-12-01

    A multiple and holistic multi-sensor monitoring of clouds and precipitation processes is a challenging but promising task in the meteorological community. Instrument synergies offer detailed views in microphysical and dynamical developments of clouds. Since 2017 The the Juelich Observatory for Cloud Evolution (JOYCE) is transformed into a Core Facility (JOYCE - CF). JOYCE - CF offers multiple long-term remote sensing observations of the atmosphere, develops an easy access to all observations and invites scientists word wide to exploit the existing data base for their research but also to complement JOYCE-CF with additional long-term or campaign instrumentation. The major instrumentation contains a twin set of two polarimetric X-band radars, a microwave profiler, two cloud radars, an infrared spectrometer, a Doppler lidar and two ceilometers. JOYCE - CF offers easy and open access to database and high quality calibrated observations of all instruments. E.g. the two polarimetric X-band radars which are located in 50 km distance are calibrated using the self-consistency method, frequently repeated vertical pointing measurements as well as instrument synergy with co-located micro-rain radar and distrometer measurements. The presentation gives insights into calibration procedures, the standardized operation procedures and recent synergistic research exploiting our radars operating at three different frequencies.

  16. Non-Invasive Evaluation of Cystic Fibrosis Related Liver Disease in Adults with ARFI, Transient Elastography and Different Fibrosis Scores

    PubMed Central

    Oltmanns, Annett; Güttler, Andrea; Petroff, David; Wirtz, Hubert; Mainz, Jochen G.; Mössner, Joachim; Berg, Thomas; Tröltzsch, Michael; Keim, Volker; Wiegand, Johannes

    2012-01-01

    Background Cystic fibrosis-related liver disease (CFLD) is present in up to 30% of cystic fibrosis patients and can result in progressive liver failure. Diagnosis of CFLD is challenging. Non-invasive methods for staging of liver fibrosis display an interesting diagnostic approach for CFLD detection. Aim We evaluated transient elastography (TE), acoustic radiation force impulse imaging (ARFI), and fibrosis indices for CFLD detection. Methods TE and ARFI were performed in 55 adult CF patients. In addition, AST/Platelets-Ratio-Index (APRI), and Forns' score were calculated. Healthy probands and patients with alcoholic liver cirrhosis served as controls. Results Fourteen CF patients met CFLD criteria, six had liver cirrhosis. Elastography acquisition was successful in >89% of cases. Non-cirrhotic CFLD individuals showed elastography values similar to CF patients without liver involvement. Cases with liver cirrhosis differed significantly from other CFLD patients (ARFI: 1.49 vs. 1.13 m/s; p = 0.031; TE: 7.95 vs. 4.16 kPa; p = 0.020) and had significantly lower results than individuals with alcoholic liver cirrhosis (ARFI: 1.49 vs. 2.99 m/s; p = 0.002). APRI showed the best diagnostic performance for CFLD detection (AUROC 0.815; sensitivity 85.7%, specificity 70.7%). Conclusions ARFI, TE, and laboratory based fibrosis indices correlate with each other and reliably detect CFLD related liver cirrhosis in adult CF patients. CF specific cut-off values for cirrhosis in adults are lower than in alcoholic cirrhosis. PMID:22848732

  17. State performance in pluripotent and adult stem cell research, 2009-2016.

    PubMed

    Surani, Sana H; Levine, Aaron D

    2018-04-01

    To examine how the geographic distribution of pluripotent and adult stem cell research publications within the USA differs from other areas of biomedical research. Publication count data for pluripotent stem cell research, adult stem cell research and a comparison group representative of biomedical research more broadly were collected and analyzed for each US state from 2009 to 2016. The distribution of pluripotent stem cell research differed from the other fields with overperformance in pluripotent stem cell research observed in California, as well as Wisconsin, Massachusetts, Maryland and Connecticut. Our analysis suggests that permissive state stem cell policy may be one of the several factors contributing to strong state performance in pluripotent stem cell research.

  18. Associations of Dairy Intake with Arterial Stiffness in Brazilian Adults: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

    PubMed

    Ribeiro, Amanda Gomes; Mill, José Geraldo; Cade, Nágela Valadão; Velasquez-Melendez, Gustavo; Matos, Sheila Maria Alvim; Molina, Maria Del Carmen Bisi

    2018-05-31

    Recent studies have suggested the possible effect of dairy product intake on cardiovascular risk markers, including arterial stiffness. Our aim was to investigate whether dairy food intake is associated with arterial stiffness, which we assessed by carotid-femoral pulse wave velocity (cfPWV) and pulse pressure (PP) in a cross-sectional analysis of baseline data (2008⁻2010; n = 12,892) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Dairy consumption was evaluated with a validated food-frequency questionnaire (FFQ) by computing servings per day for total and subgroups of dairy products. Dairy consumption was described in four categories (≤1 serving/day to >4 servings/day). Covariance analysis (ANCOVA) was used to compare cfPWV across increasing intake of dairy food, adjusting for confounding factors, including non-dairy food groups. The intake of total dairy was inversely associated with cfPWV and PP (-0.13 m/s and -1.3 mmHg, from the lowest and to the highest category of dairy intake). Low-fat dairy, fermented dairy and cheese showed an inverse relationship with cfPWV and PP. These findings suggest a beneficial effect of dairy consumption to reduce arterial stiffness. However, further evidence from longitudinal studies or long-term intervention is needed to support reduction of cfPWV and PP mediating the beneficial effects of dairy products on cardiovascular health.

  19. Diagnostic Yield of 2 Strategies for Adult Celiac Disease Identification in Primary Care.

    PubMed

    Scoglio, Riccardo; Trifirò, Gianluca; Sandullo, Antonino; Marangio, Giovanni; D'Agate, Cinzia; Costa, Stefano; Pellegrino, Salvatore; Alibrandi, Angela; Aiello, Andrea; Currò, Giovanni; Cuzzupè, Chiara; Comisi, Fabrizio; Amato, Salvatore; Conti Nibali, Roberto; Oteri, Sergio; Magazzu, Giuseppe; Carroccio, Antonio

    2017-12-18

    To compare the diagnostic yield and cost-consequences of 2 strategies, screening regardless of symptoms versus case finding (CF), using a point-of-care test (POCT), for the detection of celiac disease (CD) in primary care, to bridge the diagnostic gap of CD in adults. All subjects under 75 years of age who consecutively went to their general practitioners' offices were offered POCT for anti-transglutaminase immunoglobulin A antibodies. The POCT was performed on all subjects who agreed, and then a systematic search for symptoms or conditions associated with higher risk for CD was performed, immediately after the test but before knowing the test results. The 2 resulting groups were: (a) POCT positive and (b) symptomatic subject at CF. Subjects were defined as symptomatic at CF in the presence of 1 or more symptoms. All POCT-positive or symptomatic subjects at CF were referred to the CD Centers for confirmation of CD. Data on resource consumption were gathered from patients' charts. Cost of examinations, and diagnostic and laboratory tests were estimated with regional outpatient tariffs (Sicily), and a price of &OV0556;2.5 was used for each POCT. Of a total of 2197 subjects who agreed to participate in the study, 36 (1.6%) and 671 (30.5%) were POCT positive and symptomatic at CF, respectively. The yield from the screening and CF was 5 new celiac patients. The total cost and mean cost for each new CD case were &OV0556;7497.35 and &OV0556;1499.47 for the POCT screening strategy, and &OV0556;9855.14 and &OV0556;1971.03 for the CF strategy, respectively. Assuming consecutive use of both strategies, performing POCT only in symptomatic subjects at CF, the calculated yield would be 4 new diagnoses with a total cost of &OV0556;2345.84 and a mean cost of &OV0556;586.46 for each newly diagnosed patient. Only 1 patient was celiac despite a negative POCT. Testing symptomatic subjects at CF only by POCT seems the most cost-effective strategy to bridge the diagnostic gap of adult

  20. Mutational Landscape of cfDNA Identifies Distinct Molecular Features Associated With Therapeutic Response to First-Line Platinum-Based Doublet Chemotherapy in Patients with Advanced NSCLC

    PubMed Central

    Jiang, Tao; Li, Xuefei; Wang, Jianfei; Su, Chunxia; Han, Wenbo; Zhao, Chao; Wu, Fengying; Gao, Guanghui; Li, Wei; Chen, Xiaoxia; Li, Jiayu; Zhou, Fei; Zhao, Jing; Cai, Weijing; Zhang, Henghui; Du, Bo; Zhang, Jun; Ren, Shengxiang; Zhou, Caicun; Yu, Hui; Hirsch, Fred R.

    2017-01-01

    Rationale To investigate whether the mutational landscape of circulating cell-free DNA (cfDNA) could predict and dynamically monitor the response to first-line platinum-based chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods Eligible patients were included and blood samples were collected from a phase III trial. Both cfDNA fragments and fragmented genomic DNA were extracted for enrichment in a 1.15M size panel covering exon regions of 1,086 genes. Molecular mutational burden (MMB) was calculated to investigate the relationship between molecular features of cfDNA and response to chemotherapy. Results In total, 52 eligible cases were enrolled and their blood samples were prospectively collected at baseline, every cycle of chemotherapy and time of disease progression. At baseline, alterations of 17 genes were found. Patients with partial response (PR) had significantly lower baseline MMB of these genes than those patients with either stable disease (SD) (P = 0.0006) or progression disease (PD) (P = 0.0074). Further analysis revealed that the mutational landscape of cfDNA from pretreatment blood samples were distinctly different among patients with PR vs. SD/PD. For patients with baseline TP53 mutation, those with PR experienced a significant reduction in MMB whereas patients with SD or PD experienced an increase after two, three or four cycles of chemotherapy. Furthermore, patients with low MMB had superior response rate and significantly longer progression-free survival than those with high MMB. Conclusion This study indicated that the mutational landscape of cfDNA has potential clinical value to predict the therapeutic response to first-line platinum-based doublet chemotherapy in NSCLC patients. At the single gene level, dynamic change of molecular mutational burden of TP53 is valuable to monitor efficacy (and, therefore, might aid in early recognition of resistance and relapse) in patients harboring this mutation at baseline. PMID

  1. Alternative Cell Sources to Adult Hepatocytes for Hepatic Cell Therapy.

    PubMed

    Pareja, Eugenia; Gómez-Lechón, María José; Tolosa, Laia

    2017-01-01

    Adult hepatocyte transplantation is limited by scarce availability of suitable donor liver tissue for hepatocyte isolation. New cell-based therapies are being developed to supplement whole-organ liver transplantation, to reduce the waiting-list mortality rate, and to obtain more sustained and significant metabolic correction. Fetal livers and unsuitable neonatal livers for organ transplantation have been proposed as potential useful sources of hepatic cells for cell therapy. However, the major challenge is to use alternative cell sources for transplantation that can be derived from reproducible methods. Different types of stem cells with hepatic differentiation potential are eligible for generating large numbers of functional hepatocytes for liver cell therapy to treat degenerative disorders, inborn hepatic metabolic diseases, and organ failure. Clinical trials are designed to fully establish the safety profile of such therapies and to define target patient groups and standardized protocols.

  2. Intracavitary moderator balloon combined with 252Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations

    PubMed Central

    Brandão, S F

    2015-01-01

    Objective: This article proposes a combination of californium-252 (252Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Methods: Dosimetric evaluations were performed on three protocol set-ups: 252Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Results: Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0–5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Conclusion: Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the 252Cf source, sparing the normal brain tissue. Advances in knowledge: Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis. PMID:25927876

  3. Induced adult stem (iAS) cells and induced transit amplifying progenitor (iTAP) cells-a possible alternative to induced pluripotent stem (iPS) cells?

    PubMed

    Heng, Boon Chin; Richards, Mark; Ge, Zigang; Shu, Yimin

    2010-02-01

    The successful derivation of iPSC lines effectively demonstrates that it is possible to reset the 'developmental clock' of somatic cells all the way back to the initial embryonic state. Hence, it is plausible that this clock may instead be turned back half-way to a less immature developmental stage that is more directly applicable to clinical therapeutic applications or for in vitro pharmacology/toxicology screening assays. Such a suitable developmental state is postulated to be either the putative transit amplifying progenitor stage or adult stem cell stage. It is hypothetically possible to reprogram mature and terminally differentiated somatic cells back to the adult stem cell or transit amplifying progenitor stage, in a manner similar to the derivation of iPSC. It is proposed that the terminology 'Induced Adult Stem Cells' (iASC) or 'Induced Transit Amplifying Progenitor Cells' (iTAPC) be used to described such reprogrammed somatic cells. Of particular interest, is the possibility of resetting the developmental clock of mature differentiated somatic cells of the mesenchymal lineage, explanted from adipose tissue, bone marrow and cartilage. The putative adult stem cell sub-population from which these cells are derived, commonly referred to as 'mesenchymal stem cells', are highly versatile and hold much therapeutic promise in regenerative medicine, as attested to by numerous human clinical trials and animal studies. Perhaps it may be appropriate to term such reprogrammed cells as 'Induced Mesenchymal Stem Cells' (iMSC) or as 'Induced Mesenchumal Progenitor Cells' (iMPC). Given that cells from the same organ/tissue will share some commonalities in gene expression, we hypothesize that the generation of iASC or iTAPC would be more efficient as compared to iPSC generation, since a common epigenetic program must exist between the reprogrammed cells, adult stem cell or progenitor cell types and terminally differentiated cell types from the same organ/tissue.

  4. First record of a digenean from invasive lionfish, Pterois cf. volitans, (Scorpaeniformes: Scorpaenidae) in the northwestern Atlantic Ocean.

    PubMed

    Bullard, S A; Barse, A M; Curran, S S; Morris, J A

    2011-10-01

    Adults of Lecithochirium floridense (Digenea: Hemiuridae) parasitized the stomach in each of 22 necropsied lionfish, Pterois cf. volitans (Scorpaeniformes: Scorpaenidae) (prevalence  =  100%, mean intensity  =  11), captured in the northwestern Atlantic Ocean off Beaufort, North Carolina (34°14.83'N, 76°35.25'W). This is the first report of a digenean from the invasive lionfish and that of L. floridense from a species of Pterois. The leech specimen previously identified as Myzobdella lugubris from P. volitans in the northwestern Atlantic Ocean is re-identified as Trachelobdella lubrica based on a study of the original voucher specimen.

  5. Supervised physical exercise improves clinical, anthropometric and biochemical parameters in adult cystic fibrosis patients: A 2-year evaluation.

    PubMed

    Elce, Ausilia; Nigro, Ersilia; Gelzo, Monica; Iacotucci, Paola; Carnovale, Vincenzo; Liguori, Renato; Izzo, Viviana; Corso, Gaetano; Castaldo, Giuseppe; Daniele, Aurora; Zarrilli, Federica

    2018-03-30

    Cystic fibrosis (CF) is the most common inherited, life limiting condition among Caucasians. No healing therapy is currently available for patients with CF. The aim of the study was to define clinical, anthropometric and biochemical effects of regular, supervised physical exercise in a large cohort of patients with CF. Fifty-nine adult patients with CF that performed regularly supervised physical exercise in the last 3 years in comparison to 59 sex and age matched sedentary patients with CF were included in the study. Physical exercise had significantly beneficial effects on: (a) FEV1% decline; (b) anthropometric parameters (lower number of cases with altered BMI, waist and arm circumferences); (c) lipid and glucose metabolism; (d) vitamin D serum levels. Of course, some of this improvement may be because of the better adherence to therapy typical of patients with CF that perform physical activity. Such clinical and metabolic effects make supervised physical activity one of the hubs in managing patients with CF. © 2018 John Wiley & Sons Ltd.

  6. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    NASA Astrophysics Data System (ADS)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  7. The Satellite Cell in Male and Female, Developing and Adult Mouse Muscle: Distinct Stem Cells for Growth and Regeneration

    PubMed Central

    Neal, Alice; Boldrin, Luisa; Morgan, Jennifer Elizabeth

    2012-01-01

    Satellite cells are myogenic cells found between the basal lamina and the sarcolemma of the muscle fibre. Satellite cells are the source of new myofibres; as such, satellite cell transplantation holds promise as a treatment for muscular dystrophies. We have investigated age and sex differences between mouse satellite cells in vitro and assessed the importance of these factors as mediators of donor cell engraftment in an in vivo model of satellite cell transplantation. We found that satellite cell numbers are increased in growing compared to adult and in male compared to female adult mice. We saw no difference in the expression of the myogenic regulatory factors between male and female mice, but distinct profiles were observed according to developmental stage. We show that, in contrast to adult mice, the majority of satellite cells from two week old mice are proliferating to facilitate myofibre growth; however a small proportion of these cells are quiescent and not contributing to this growth programme. Despite observed changes in satellite cell populations, there is no difference in engraftment efficiency either between satellite cells derived from adult or pre-weaned donor mice, male or female donor cells, or between male and female host muscle environments. We suggest there exist two distinct satellite cell populations: one for muscle growth and maintenance and one for muscle regeneration. PMID:22662253

  8. Intra-individual biological variation in sweat chloride concentrations in CF, CFTR dysfunction, and healthy pediatric subjects.

    PubMed

    Cirilli, Natalia; Raia, Valeria; Rocco, Ilaria; De Gregorio, Fabiola; Tosco, Antonella; Salvadori, Laura; Sepe, Angela Ornella; Buzzetti, Roberto; Minicuci, Nadia; Castaldo, Giuseppe

    2018-04-02

    The sweat test is one of the main diagnostic tools used in newborn screening programs and as a confirmatory test, in case of suspect of Cystic Fibrosis (CF). Since sweat chloride (Cl) concentration is also considered an appropriate parameter to explore the efficacy of CFTR modulators in clinical trials, it is crucial to evaluate the biological variability of this test in healthy and pathological conditions. The aim of this pilot study was to determine the intra-individual biological variability of sweat Cl, both in healthy individuals and CF patients and to assess its correlation with diet, season, and menstrual cycle. Thirty-five out of 36 selected subjects (6-18 years) were enrolled by 2 CF care centers and assigned to 3 cohorts: CF, CFTR-related disorder (CFTR-RD) and healthy volunteers. Each participant was subjected to eight sweat tests in different conditions and time of the year. Data were analyzed using linear mixed effects models for repeated measures, taking also into account intra-individual correlations. We observed a high intra-individual variability of sweat Cl, with the lowest mean CV% values among CF patients (20.21 in CF, 29.74 in CFTR-RD, and 31.15 in healthy subjects). Gender and diet had no influence on sweat Cl variability, nor had pubertal age and menstrual phase. Results of this pilot study confirmed that sweat Cl variability is high in CF patients, although non-CF individuals displayed even higher mean CV% values. Season significantly influenced sweat test values only in CF patients, likely due to changes in their hydration status. © 2018 Wiley Periodicals, Inc.

  9. Identification, Characterization, and Utilization of Adult Meniscal Progenitor Cells

    DTIC Science & Technology

    2015-09-01

    the development of knee osteoarthritis (OA). New treatments centered on the stem/progenitor cell population resident within the adult meniscus will be...cells, stem cells, progenitor cells, meniscus healing, meniscus repair, osteoarthritis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...changes that occur after injury. As a result, meniscal injuries are a common underlying cause of post-traumatic osteoarthritis . This is particularly

  10. Measuring the Carotid to Femoral Pulse Wave Velocity (Cf-PWV) to Evaluate Arterial Stiffness.

    PubMed

    Ji, Hongwei; Xiong, Jing; Yu, Shikai; Chi, Chen; Bai, Bin; Teliewubai, Jiadela; Lu, Yuyan; Zhang, Yi; Xu, Yawei

    2018-05-03

    For the elderly, arterial stiffening is a good marker for aging evaluation and it is recommended that the arterial stiffness be determined noninvasively by the measurement of carotid to femoral pulse wave velocity (cf-PWV) (Class I; Level of Evidence A). In literature, numerous community-based or disease-specific studies have reported that higher cf-PWV is associated with increased cardiovascular risk. Here, we discuss strategies to evaluate arterial stiffness with cf-PWV. Following the well-defined steps detailed here, e.g., proper position operator, distance measurement, and tonometer position, we will obtain a standard cf-PWV value to evaluate arterial stiffness. In this paper, a detailed stepwise method to record a good quality PWV and pulse wave analysis (PWA) using a non-invasive tonometry-based device will be discussed.

  11. Differential muscle regulatory factor gene expression between larval and adult myogenesis in the frog Xenopus laevis: adult myogenic cell-specific myf5 upregulation and its relation to the notochord suppression of adult muscle differentiation.

    PubMed

    Yamane, Hitomi; Nishikawa, Akio

    2013-08-01

    During Xenopus laevis metamorphosis, larval-to-adult muscle conversion depends on the differential responses of adult and larval myogenic cells to thyroid hormone. Essential differences in cell growth, differentiation, and hormone-dependent life-or-death fate have been reported between cultured larval (tail) and adult (hindlimb) myogenic cells. A previous study revealed that tail notochord cells suppress terminal differentiation in adult (but not larval) myogenic cells. However, little is known about the differences in expression patterns of myogenic regulatory factors (MRF) and the satellite cell marker Pax7 between adult and larval myogenic cells. In the present study, we compared mRNA expression of these factors between the two types. At first, reverse transcription polymerase chain reaction analysis of hindlimb buds showed sequential upregulation of myf5, myogenin, myod, and mrf4 during stages 50-54, when limb buds elongate and muscles begin to form. By contrast, in the tail, there was no such increase during the same period. Secondary, these results were duplicated in vitro: adult myogenic cells upregulated myf5, myod, and pax7 in the early culture period, followed by myogenin upregulation and myotube differentiation, while larval myogenic cells did not upregulate these genes and precociously started myotube differentiation. Thirdly, myf5 upregulation and early-phase proliferation in adult myogenic cells were potently inhibited by the presence of notochord cells, suggesting that notochord cells suppress adult myogenesis through inhibiting the transition from Myf5(-) stem cells to Myf5(+) committed myoblasts. All of the data presented here suggest that myf5 upregulation can be a good criterion for the activation of adult myogenesis during X. laevis metamorphosis.

  12. Identification and characterization of putative stem cells in the adult pig ovary.

    PubMed

    Bui, Hong-Thuy; Van Thuan, Nguyen; Kwon, Deug-Nam; Choi, Yun-Jung; Kang, Min-Hee; Han, Jae-Woong; Kim, Teoan; Kim, Jin-Hoi

    2014-06-01

    Recently, the concept of 'neo-oogenesis' has received increasing attention, since it was shown that adult mammals have a renewable source of eggs. The purpose of this study was to elucidate the origin of these eggs and to confirm whether neo-oogenesis continues throughout life in the ovaries of the adult mammal. Adult female pigs were utilized to isolate, identify and characterize, including their proliferation and differentiation capabilities, putative stem cells (PSCs) from the ovary. PSCs were found to comprise a heterogeneous population based on c-kit expression and cell size, and also express stem and germ cell markers. Analysis of PSC molecular progression during establishment showed that these cells undergo cytoplasmic-to-nuclear translocation of Oct4 in a manner reminiscent of gonadal primordial germ cells (PGCs). Hence, cells with the characteristics of early PGCs are present or are generated in the adult pig ovary. Furthermore, the in vitro establishment of porcine PSCs required the presence of ovarian cell-derived extracellular regulatory factors, which are also likely to direct stem cell niche interactions in vivo. In conclusion, the present work supports a crucial role for c-kit and kit ligand/stem cell factor in stimulating the growth, proliferation and nuclear reprogramming of porcine PSCs, and further suggests that porcine PSCs might be the culture equivalent of early PGCs. © 2014. Published by The Company of Biologists Ltd.

  13. Final Technical Report for grant entitled "New Horizons in C-F Activation by Main Group Electrophiles"

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

    Ozerov, Oleg V; Ozerov, Oleg V.

    2014-01-16

    We became interested in developing new methods for hydrodefluorination (HDF) and other types of C-F bond conversion in polyfluoroalkanes under mild conditions. We were attracted to an approach to C-F activation, where the key C-F cleavage proceeds by a Lewis acid abstraction of fluoride rather than a redox event. The efforts during the previous period were aimed at a) advancing the HDF reactivity with improvement in scope and catalyst longevity; b) extending C-F activation beyond HDF; c) generating insight about the elementary steps of the reaction and potential intermediates.

  14. Physiological Plasticity of Neural-Crest-Derived Stem Cells in the Adult Mammalian Carotid Body.

    PubMed

    Annese, Valentina; Navarro-Guerrero, Elena; Rodríguez-Prieto, Ismael; Pardal, Ricardo

    2017-04-18

    Adult stem cell plasticity, or the ability of somatic stem cells to cross boundaries and differentiate into unrelated cell types, has been a matter of debate in the last decade. Neural-crest-derived stem cells (NCSCs) display a remarkable plasticity during development. Whether adult populations of NCSCs retain this plasticity is largely unknown. Herein, we describe that neural-crest-derived adult carotid body stem cells (CBSCs) are able to undergo endothelial differentiation in addition to their reported role in neurogenesis, contributing to both neurogenic and angiogenic processes taking place in the organ during acclimatization to hypoxia. Moreover, CBSC conversion into vascular cell types is hypoxia inducible factor (HIF) dependent and sensitive to hypoxia-released vascular cytokines such as erythropoietin. Our data highlight a remarkable physiological plasticity in an adult population of tissue-specific stem cells and could have impact on the use of these cells for cell therapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Langmuir Probe Measurements in an Inductively Coupled Ar/CF4 Plasmas

    NASA Technical Reports Server (NTRS)

    Rao, M. V. V. S.; Meyyappan, M.; Sharma, S. P.; Arnold, James O. (Technical Monitor)

    2000-01-01

    Technological advancement in the microelectronics industry requires an understanding of the physical and chemical processes occurring in plasmas of fluorocarbon gases, such as carbon tetrafluoride (CF4) which is commonly used as an etchant, and their mixtures to optimize various operating parameters. In this paper we report data on electron number density (ne), electron temperature'(Te), electron energy distribution function (EEDF), mean electron energy, ion number density (ni), and plasma potential (Vp) measured by using Langmuir probe in an inductively coupled 13.56 MHz radio frequency plasmas generated in 50%Ar:50%CF4 mixture in the GEC cell. The probe data were recorded at various radial positions providing radial profiles of these plasma parameters at 10-50 mTorr pressures and 200 W and 300 W of RF power. Present measurements indicate that the electron and ion number densities increase with increase in pressure and power. Whereas the plasma potential and electron temperature decrease with increase in pressure, and they weakly depend on RF power. The radial profiles exhibit that the electron and ion number densities and the plasma potential peak at the center of the plasma with an exponential fall away from it, while the electron temperature has a minimum at the center and it increases steadily towards the electrode edge. The EEDFs have a characteristic drop near the low energy end at all pressures and pressures and their shapes represent non-Maxwellian plasma and exhibit more like Druyvesteyn energy distribution.v

  16. N-point correlation functions in the CfA and SSRS redshift distribution of galaxies

    NASA Technical Reports Server (NTRS)

    Gaztanaga, Enrique

    1992-01-01

    Using counts in cells, we estimate the volume-average N-point galaxy correlation functions for N = 2, 3, and 4, in redshift samples of the CfA and SSRS catalogs. Volume-limited samples of different sizes are used to study the uncertainties at different scales, the shot noise, and the problem with the boundaries. The hierarchical constants S3 and S4 agree well in all samples in CfA and SSRS, with average S3 = 194 +/- 0.07 and S4 = 4.56 +/- 0.53. We compare these results with estimates obtained from angular catalogs and recent analysis over IRAS samples. The amplitudes SJ seem larger in real space than in redshift space, although the values from the angular analysis correspond to smaller scales, where we might expect larger nonperturbative effects. It is also found that S3 and S4 are smaller for IRAS than for optical galaxies. This, together with the fact that IRAS galaxies have smaller amplitude for the above correlation functions, indicates that the density fluctuations of IRAS galaxies cannot be simply proportional to the density fluctuations of optical galaxies, i.e., biasing has to be nonlinear between them.

  17. Fatty acyltranferases in serum in cystic fibrosis (CF) patients

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

    Zielenski, J.; Newman, L.J.; Slomiany, B.L.

    1987-05-01

    Studies on serum and gastrointestinal secretion from CF patient is suggest that defective accumulation of mucus in gastrointestinal tract and excessive amount of a protease resistant peptides in serum are related to the abnormal activity of enzymes responsible for fatty acylation of proteins. Here, the authors investigated the fatty acyltransferase activities in serum of normal and CF patients. A 15 l of serum was mixed with 0.85 nmol ( UC)palmitoyl CoA, 200 g of serine and threonine and incubated at 37C for 30 min. The incubates were immediately frozen, dried extracted with C/M and chromatographed in chloroform/methanol/water. The incorporation ofmore » ( UC)palmitate was determined using linear radioscanner and authoradiography. The results of HPTLC revealed that CF serum in addition of ACAT and LCAT contained enzymes responsible for the transfer of ( UC)palmitate to monoacylphosphoglycerides, and serine and threonine. In normal serum the formation of a small amount of palmitoyl serine and palmitoyl threonine was also observed but the acylation of monoacylphosphoglycerides was not detectable. The authors conclude that in cystic fibrosis the abnormal fatty acyltransferases are responsible for the occurrence of protease resistant glycoprotein, unusual peptides in serum and possibly for the modification of membrane proteins and lipids.« less

  18. Effect of oxidative insult on young and adult cardiac muscle cells in vitro.

    PubMed

    Nag, A C; Sreepathi, P; Lee, M L; Reddan, J R

    1996-01-01

    The effect of hydrogen peroxide on cultured neonatal and adult cardiac myocytes was investigated. On neonatal cardiac myocytes the effect was very pronounced at a low concentration (0.03 mM), whereas the adult cardiac myocytes were resistant to the same concentration of H2O2. Dividing neonatal cardiac myocytes were more susceptible to H2O2 insult than the non-dividing adult cardiac myocytes. At a concentration of 0.1 mM H2O2, the neonatal cardiac myocytes were significantly damaged compared with the adult cardiac myocytes. Cardiac muscle cells from neonatal and adult hearts at high density culture were more tolerant to the oxidative insult by H2O2 than cells in low density culture. The damaging effect of H2O2 was very selective on F-actin in neonatal and adult cardiac muscle cells. The effect of H2O2 on myosin, titin, alpha-actinin, desmin or tubulin was not pronounced. Microscopical studies suggested a more marked protection by catalase than by glutathione reductase in the neonatal cells.

  19. Costs of treatment of adult patients with cystic fibrosis in Poland and internationally.

    PubMed

    Kopciuch, Dorota; Zaprutko, Tomasz; Paczkowska, Anna; Nowakowska, Elżbieta

    2017-07-01

    Despite its low prevalence, cystic fibrosis (CF) may have a considerable impact on healthcare system expenditures in terms of direct healthcare costs and lost productivity. This study was aimed at calculation of costs associated with CF treatment in Poland, as well as at comparison of average costs of treatment of CF patients in selected countries, taking into account the purchasing power parity. Retrospective study. The researchers undertook a retrospective study of adult patients with CF taking into account the broadest social perspective possible. Medical and non-medical direct costs as well as indirect costs were calculated. CF costs estimated by researchers from other countries over the last 15 years were also compared. Total annual treatment cost per one CF patient in Poland was on average EUR 19,581.08. Costs of treatment of CF patients over the last 15 years varied between the countries and ranged from EUR 23,330.82 in Bulgaria to EUR 68,696.42 in the United States. CF is an international problem. The data in this study could be the baseline for integrated and harmonised approaches for periodical assessment of the future impact of new public policies and interventions for rare diseases at the national and international levels. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  20. Skin-infiltrating, interleukin-22-producing T cells differentiate pediatric psoriasis from adult psoriasis.

    PubMed

    Cordoro, Kelly M; Hitraya-Low, Maria; Taravati, Keyon; Sandoval, Priscila Munoz; Kim, Esther; Sugarman, Jeffrey; Pauli, Mariela L; Liao, Wilson; Rosenblum, Michael D

    2017-09-01

    Evidence from adult psoriasis studies implicates an imbalance between regulatory and effector T cells, particularly T H -17-producing T cells, in the pathogenesis of psoriasis. Little is known about the immunopathology of psoriasis in children. We sought to functionally characterize the inflammatory cell profiles of psoriatic plaques from pediatric patients and compare them with healthy, age-matched controls and adult psoriasis patients. Skin samples from pediatric psoriasis patients and healthy controls were analyzed by multiparameter flow cytometry to determine the dominant immune cell subsets present and cytokines produced. Lesional tissue from pediatric psoriasis patients had significantly increased interleukin (IL) 22 derived from CD4 + and CD8 + cells compared with the tissues from healthy pediatric controls and adult psoriasis patients. Tissue from pediatric psoriasis patients had significantly less elevation of IL-17 derived from CD4 + and CD8 + cells compared with the tissue from adult psoriasis patients. In contrast with the lesions from adult patients, lesional skin in pediatric patients with psoriasis did not have increases in regulatory T cells. This is a pilot study, thus the sample size is small. Significant differences in IL-17 and IL-22 expression were observed in the pediatric psoriasis patients compared with pediatric healthy controls and adult psoriasis patients. IL-22 might be relevant in the pathogenesis of pediatric psoriasis and represents a potential treatment target unique to pediatric psoriasis. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  1. huJCAR014 CAR-T Cells in Treating Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2018-05-25

    Adult B Acute Lymphoblastic Leukemia; BCL2 Gene Rearrangement; BCL6 Gene Rearrangement; CD19 Positive; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; MYC Gene Rearrangement; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Adult Acute Lymphoblastic Leukemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  2. Dogs cloned from adult somatic cells.

    PubMed

    Lee, Byeong Chun; Kim, Min Kyu; Jang, Goo; Oh, Hyun Ju; Yuda, Fibrianto; Kim, Hye Jin; Hossein, M Shamim; Shamim, M Hossein; Kim, Jung Ju; Kang, Sung Keun; Schatten, Gerald; Hwang, Woo Suk

    2005-08-04

    Several mammals--including sheep, mice, cows, goats, pigs, rabbits, cats, a mule, a horse and a litter of three rats--have been cloned by transfer of a nucleus from a somatic cell into an egg cell (oocyte) that has had its nucleus removed. This technology has not so far been successful in dogs because of the difficulty of maturing canine oocytes in vitro. Here we describe the cloning of two Afghan hounds by nuclear transfer from adult skin cells into oocytes that had matured in vivo. Together with detailed sequence information generated by the canine-genome project, the ability to clone dogs by somatic-cell nuclear transfer should help to determine genetic and environmental contributions to the diverse biological and behavioural traits associated with the many different canine breeds.

  3. Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing.

    PubMed

    Tang, Qin; Iyer, Sowmya; Lobbardi, Riadh; Moore, John C; Chen, Huidong; Lareau, Caleb; Hebert, Christine; Shaw, McKenzie L; Neftel, Cyril; Suva, Mario L; Ceol, Craig J; Bernards, Andre; Aryee, Martin; Pinello, Luca; Drummond, Iain A; Langenau, David M

    2017-10-02

    Recent advances in single-cell, transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. In this study, we used massively parallel, single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis and functionally distinct renal cells found in adult zebrafish. Because our method analyzed blood and kidney cells in an unbiased manner, our approach was useful in characterizing immune-cell deficiencies within DNA-protein kinase catalytic subunit ( prkdc ), interleukin-2 receptor γ a ( il2rga ), and double-homozygous-mutant fish, identifying blood cell losses in T, B, and natural killer cells within specific genetic mutants. Our analysis also uncovered novel cell types, including two classes of natural killer immune cells, classically defined and erythroid-primed hematopoietic stem and progenitor cells, mucin-secreting kidney cells, and kidney stem/progenitor cells. In total, our work provides the first, comprehensive, single-cell, transcriptomic analysis of kidney and marrow cells in the adult zebrafish. © 2017 Tang et al.

  4. Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing

    PubMed Central

    Iyer, Sowmya; Lobbardi, Riadh; Chen, Huidong; Hebert, Christine; Shaw, McKenzie L.; Neftel, Cyril; Suva, Mario L.; Bernards, Andre; Aryee, Martin; Drummond, Iain A.

    2017-01-01

    Recent advances in single-cell, transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. In this study, we used massively parallel, single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis and functionally distinct renal cells found in adult zebrafish. Because our method analyzed blood and kidney cells in an unbiased manner, our approach was useful in characterizing immune-cell deficiencies within DNA–protein kinase catalytic subunit (prkdc), interleukin-2 receptor γ a (il2rga), and double-homozygous–mutant fish, identifying blood cell losses in T, B, and natural killer cells within specific genetic mutants. Our analysis also uncovered novel cell types, including two classes of natural killer immune cells, classically defined and erythroid-primed hematopoietic stem and progenitor cells, mucin-secreting kidney cells, and kidney stem/progenitor cells. In total, our work provides the first, comprehensive, single-cell, transcriptomic analysis of kidney and marrow cells in the adult zebrafish. PMID:28878000

  5. Long-term in vivo single-cell tracking reveals the switch of migration patterns in adult-born juxtaglomerular cells of the mouse olfactory bulb

    PubMed Central

    Liang, Yajie; Li, Kaizhen; Riecken, Kristoffer; Maslyukov, Anatoliy; Gomez-Nicola, Diego; Kovalchuk, Yury; Fehse, Boris; Garaschuk, Olga

    2016-01-01

    The behavior of adult-born cells can be easily monitored in cell culture or in lower model organisms, but longitudinal observation of individual mammalian adult-born cells in their native microenvironment still proves to be a challenge. Here we have established an approach named optical cell positioning system for long-term in vivo single-cell tracking, which integrates red-green-blue cell labeling with repeated angiography. By combining this approach with in vivo two-photon imaging technique, we characterized the in vivo migration patterns of adult-born neurons in the olfactory bulb. In contrast to the traditional view of mere radial migration of adult-born cells within the bulb, we found that juxtaglomerular cells switch from radial migration to long distance lateral migration upon arrival in their destination layer. This unique long-distance lateral migration has characteristic temporal (stop-and-go) and spatial (migratory, unidirectional or multidirectional) patterns, with a clear cell age-dependent decrease in the migration speed. The active migration of adult-born cells coincides with the time period of initial fate determination and is likely to impact on the integration sites of adult-born cells, their odor responsiveness, as well as their survival rate. PMID:27174051

  6. GTP-Binding Proteins Inhibit cAMP Activation of Chloride Channels in Cystic Fibrosis Airway Epithelial Cells

    NASA Astrophysics Data System (ADS)

    Schwiebert, Erik M.; Kizer, Neil; Gruenert, Dieter C.; Stanton, Bruce A.

    1992-11-01

    Cystic fibrosis (CF) is a genetic disease characterized, in part, by defective regulation of Cl^- secretion by airway epithelial cells. In CF, cAMP does not activate Cl^- channels in the apical membrane of airway epithelial cells. We report here whole-cell patch-clamp studies demonstrating that pertussis toxin, which uncouples heterotrimeric GTP-binding proteins (G proteins) from their receptors, and guanosine 5'-[β-thio]diphosphate, which prevents G proteins from interacting with their effectors, increase Cl^- currents and restore cAMP-activated Cl^- currents in airway epithelial cells isolated from CF patients. In contrast, the G protein activators guanosine 5'-[γ-thio]triphosphate and AlF^-_4 reduce Cl^- currents and inhibit cAMP from activating Cl^- currents in normal airway epithelial cells. In CF cells treated with pertussis toxin or guanosine 5'-[β-thio]diphosphate and in normal cells, cAMP activates a Cl^- conductance that has properties similar to CF transmembrane-conductance regulator Cl^- channels. We conclude that heterotrimeric G proteins inhibit cAMP-activated Cl^- currents in airway epithelial cells and that modulation of the inhibitory G protein signaling pathway may have the therapeutic potential for improving cAMP-activated Cl^- secretion in CF.

  7. Canned Vegetable and Fruit Consumption Is Associated with Changes in Nutrient Intake and Higher Diet Quality in Children and Adults: National Health and Nutrition Examination Survey 2001-2010.

    PubMed

    Freedman, Marjorie R; Fulgoni, Victor L

    2016-06-01

    Canned vegetables and fruit (CV+CF) are ubiquitous throughout the food supply. Yet information regarding their specific contribution to nutrient intake and health measures is lacking. The objective of this study was to examine the association of CV+CF with nutrient intake, diet quality, anthropometric indicators of overweight/obesity, and blood pressure in a nationally representative population. A secondary analysis of cross-sectional data from 17,344 children and 24,807 adults in the National Health and Nutrition Examination Survey 2001-2010 was conducted. A dataset was developed that distinguished CV+CF consumers from nonconsumers. Diet quality was calculated using the Healthy Eating Index 2010. Regression analysis determined differences between groups. About 11% of the population consumed CV+CF on a given day. Compared with nonconsumers, child (n=2,066) and adult (n=2,746) CV+CF consumers ate more energy, and energy adjusted dietary fiber, total sugar, choline, and potassium, and less fat and saturated fat. Child consumers also ate more energy adjusted protein, vitamin A, calcium, and magnesium. Child and adult consumers and nonconsumers had comparable energy adjusted sodium and added sugar intakes. Compared with nonconsumers, the total Healthy Eating Index 2010 score was higher (P<0.001) in child (45.8±0.5 vs 43.3±0.3) and adult (49.0±0.4 vs 47.4±0.3) consumers. Covariate adjusted body weight, body mass index, waist circumference, and blood pressure were comparable in both of the child and adult groups. Results suggest CV+CF consumption was associated with higher intake of select nutrients, a higher-quality diet, and comparable adiposity measures and blood pressure. Copyright © 2016 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  8. Cross-platform comparison for the detection of RAS mutations in cfDNA (ddPCR Biorad detection assay, BEAMing assay, and NGS strategy)

    PubMed Central

    Garcia, Jessica; Forestier, Julien; Dusserre, Eric; Wozny, Anne-Sophie; Geiguer, Florence; Merle, Patrick; Tissot, Claire; Ferraro-Peyret, Carole; Jones, Frederick S.; Edelstein, Daniel L.; Cheynet, Valérie; Bardel, Claire; Vilchez, Gaelle; Xu, Zhenyu; Bringuier, Pierre Paul; Barritault, Marc; Brengle-Pesce, Karen; Guillet, Marielle; Chauvenet, Marion; Manship, Brigitte; Brevet, Marie; Rodriguez-Lafrasse, Claire; Hervieu, Valérie; Couraud, Sébastien; Walter, Thomas; Payen, Léa

    2018-01-01

    CfDNA samples from colon (mCRC) and non-small cell lung cancers (NSCLC) (CIRCAN cohort) were compared using three platforms: droplet digital PCR (ddPCR, Biorad); BEAMing/OncoBEAM™-RAS-CRC (Sysmex Inostics); next-generation sequencing (NGS, Illumina), utilizing the 56G oncology panel (Swift Biosciences). Tissue biopsy and time matched cfDNA samples were collected at diagnosis in the mCRC cohort and during 1st progression in the NSCLC cohort. Excellent matches between cfDNA/FFPE mutation profiles were observed. Detection thresholds were between 0.5–1% for cfDNA samples examined using ddPCR and NGS, and 0.03% with BEAMing. This high level of sensitivity enabled the detection of KRAS mutations in 5/19 CRC patients with negative FFPE profiles. In the mCRC cohort, comparison of mutation results obtained by testing FFPE to those obtained by testing cfDNA by ddPCR resulted in 47% sensitivity, 77% specificity, 70% positive predictive value (PPV) and 55% negative predictive value (NPV). For BEAMing, we observed 93% sensitivity, 69% specificity, 78% PPV and 90% NPV. Finally, sensitivity of NGS was 73%, specificity was 77%, PPV 79% and NPV 71%. Our study highlights the complementarity of different diagnostic approaches and variability of results between OncoBEAM™-RAS-CRC and NGS assays. While the NGS assay provided a larger breadth of coverage of the major targetable alterations of 56 genes in one run, its performance for specific alterations was frequently confirmed by ddPCR results. PMID:29765524

  9. A Prospective Evaluation of Circulating Tumor Cells and Cell-Free DNA in EGFR-Mutant Non-Small Cell Lung Cancer Patients Treated with Erlotinib on a Phase II Trial.

    PubMed

    Yanagita, Masahiko; Redig, Amanda J; Paweletz, Cloud P; Dahlberg, Suzanne E; O'Connell, Allison; Feeney, Nora; Taibi, Myriam; Boucher, David; Oxnard, Geoffrey R; Johnson, Bruce E; Costa, Daniel B; Jackman, David M; Jänne, Pasi A

    2016-12-15

    Genotype-directed therapy is the standard of care for advanced non-small cell lung cancer (NSCLC), but obtaining tumor tissue for genotyping remains a challenge. Circulating tumor cell (CTC) or cell-free DNA (cfDNA) analysis may allow for noninvasive evaluation. This prospective trial evaluated CTCs and cfDNA in EGFR-mutant NSCLC patients treated with erlotinib until progression. EGFR-mutant NSCLC patients were enrolled in a phase II trial of erlotinib. Blood was collected at baseline, every 2 months on study, and at disease progression. Plasma genotyping was performed by droplet digital PCR for EGFR19del, L858R, and T790M. CTCs were isolated by CellSave, enumerated, and analyzed by immunofluorescence for CD45 and pan-cytokeratin and EGFR and MET FISH were also performed. Rebiopsy was performed at disease progression. Sixty patients were enrolled; 44 patients discontinued therapy for disease progression. Rebiopsy occurred in 35 of 44 patients (80%), with paired CTC/cfDNA analysis in 41 of 44 samples at baseline and 36 of 44 samples at progression. T790M was identified in 23 of 35 (66%) tissue biopsies and 9 of 39 (23%) cfDNA samples. CTC analysis at progression identified MET amplification in 3 samples in which tissue analysis could not be performed. cfDNA analysis identified T790M in 2 samples in which rebiopsy was not possible. At diagnosis, high levels of cfDNA but not high levels of CTCs correlated with progression-free survival. cfDNA and CTCs are complementary, noninvasive assays for evaluation of acquired resistance to first-line EGFR TKIs and may expand the number of patients in whom actionable genetic information can be obtained at acquired resistance. Serial cfDNA monitoring may offer greater clinical utility than serial monitoring of CTCs. Clin Cancer Res; 22(24); 6010-20. ©2016 AACR. ©2016 American Association for Cancer Research.

  10. Supporting cells remove and replace sensory receptor hair cells in a balance organ of adult mice

    PubMed Central

    Bucks, Stephanie A; Cox, Brandon C; Vlosich, Brittany A; Manning, James P; Nguyen, Tot B; Stone, Jennifer S

    2017-01-01

    Vestibular hair cells in the inner ear encode head movements and mediate the sense of balance. These cells undergo cell death and replacement (turnover) throughout life in non-mammalian vertebrates. However, there is no definitive evidence that this process occurs in mammals. We used fate-mapping and other methods to demonstrate that utricular type II vestibular hair cells undergo turnover in adult mice under normal conditions. We found that supporting cells phagocytose both type I and II hair cells. Plp1-CreERT2-expressing supporting cells replace type II hair cells. Type I hair cells are not restored by Plp1-CreERT2-expressing supporting cells or by Atoh1-CreERTM-expressing type II hair cells. Destruction of hair cells causes supporting cells to generate 6 times as many type II hair cells compared to normal conditions. These findings expand our understanding of sensorineural plasticity in adult vestibular organs and further elucidate the roles that supporting cells serve during homeostasis and after injury. DOI: http://dx.doi.org/10.7554/eLife.18128.001 PMID:28263708

  11. The Development of Adult Innate Lymphoid Cells

    PubMed Central

    Yang, Qi; Bhandoola, Avinash

    2016-01-01

    Innate lymphoid cells (ILC) are a specialized family of effector lymphocytes that transcriptionally and functionally mirror effector subsets of T cells, but differ from T cells in that they lack clonally-distributed adaptive antigen receptors. Our understanding of this family of lymphocytes is still in its infancy. In this review, we summarize current understanding and discuss recent insights into the cellular and molecular events that occur during early ILC development in adult mice. We discuss how these events overlap and diverge with the early development of adaptive T cells, and how they may influence the molecular and functional properties of mature ILC. PMID:26871595

  12. Cast CF8C-Plus Stainless Steel for Turbocharger Applications

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

    Maziasz, P.J.; Shyam, A.; Evans, N.D.

    2010-06-30

    The purpose of this Cooperative Research and Development Agreement (CRADA) project is to provide the critical test data needed to qualify CF8C-Plus cast stainless steel for commercial production and use for turbocharger housings with upgraded performance and durability relative to standard commercial cast irons or stainless steels. The turbocharger technologies include, but are not limited to, heavy-duty highway diesel engines, and passenger vehicle diesel and gasoline engines. This CRADA provides additional critical high-temperature mechanical properties testing and data analysis needed to quality the new CF8C-Plus steels for turbocharger housing applications.

  13. Absence of the cystic fibrosis transmembrane regulator (Cftr) from myeloid-derived cells slows resolution of inflammation and infection.

    PubMed

    Bonfield, T L; Hodges, C A; Cotton, C U; Drumm, M L

    2012-11-01

    The absence or reduction of CFTR function causes CF and results in a pulmonary milieu characterized by bacterial colonization and unresolved inflammation. The ineffectiveness at controlling infection by species such as Pseudomonas aeruginosa suggests defects in innate immunity. Macrophages, neutrophils, and DCs have all been shown to express CFTR mRNA but at low levels, raising the question of whether CFTR has a functional role in these cells. Bone marrow transplants between CF and non-CF mice suggest that these cells are inherently different; we confirm this observation using conditional inactivation of Cftr in myeloid-derived cells. Mice lacking Cftr in myeloid cells overtly appear indistinguishable from non-CF mice until challenged with bacteria instilled into the lungs and airways, at which point, they display survival and inflammatory profiles intermediate in severity as compared with CF mice. These studies demonstrate that Cftr is involved directly in myeloid cell function and imply that these cells contribute to the pathophysiological phenotype of the CF lung.

  14. Validation of a visual analogue score (LRTI-VAS) in non-CF bronchiectasis.

    PubMed

    Altenburg, Josje; Wortel, Kim; de Graaff, Casper S; van der Werf, Tjip S; Boersma, Wim G

    2016-03-01

    Quality of life in patients with non-cystic fibrosis (non-CF) bronchiectasis is largely defined by respiratory symptoms. To date, no disease-specific tool for symptom measurement in this patient group was available. We developed the lower respiratory tract infections - visual analogue scale (LRTI-VAS) in order to quickly and conveniently quantify symptoms in non-CF bronchiectasis. This study aimed to validate LRTI-VAS for use in non-CF bronchiectasis. This study included outpatients with radiologically proven bronchiectasis and no evidence of CF. Results of LRTI-VAS were compared with other markers of disease activity {lung function parameters, oxygen saturation and three health-related quality of life questionnaires [Medical Outcomes Study Short-Form 36 Health Survey (SF-36), St Georges Respiratory Questionnaire (SGRQ) and Leicester Cough Questionnaire (LCQ)]} and validity, reliability and responsiveness were assessed. Thirty stable and 30 exacerbating participants completed the LRTI-VAS questionnaire. When testing for repeatability on two separate occasions, no statistically significant difference between total scores was found {1.4 [standard deviation (SD)] 5.3}, P = 0.16). Internal consistency was high across items (Cronbach's alpha 0.86). Correlation with SGRQ, SF-36 and LCQ total scores was high. Following antibiotic treatment, mean (SD) LRTI-VAS total score improved from 18.1 (SD 9.9) to 26.1 (SD 6.6) (P < 0.001). LRTI-VAS showed excellent validity, reliability and responsiveness to change and therefore appears a reliable tool for symptom measurement in non-CF bronchiectasis. © 2014 John Wiley & Sons Ltd.

  15. Coach to cope: feasibility of a life coaching program for young adults with cystic fibrosis.

    PubMed

    Knudsen, Karin Bæk; Pressler, Tacjana; Mortensen, Laust Hvas; Jarden, Mary; Boisen, Kirsten Arntz; Skov, Marianne; Quittner, Alexandra L; Katzenstein, Terese Lea

    2017-01-01

    Over the last two decades, lifespan has increased significantly for people living with cystic fibrosis (CF). However, several studies have demonstrated that many young adults with CF report mental health problems and poor adherence to their prescribed treatments, challenging their long-term physical health. Treatment guidelines recommend interventions to improve adherence and self-management. The aim of this study was to test the feasibility of a life coaching intervention for young adults with CF. A randomized, controlled feasibility study was conducted at the CF Center at Copenhagen University Hospital, Rigshospitalet. Participants were young adults with CF, aged 18-30 years without severe intellectual impairments. Participants were randomized to either life coaching or standard care. The intervention consisted of up to 10 individual, face-to-face or telephone coaching sessions over a period of 1 year. Primary outcomes were recruitment success, acceptability, adherence to the intervention, and retention rates. Secondary outcome measures included health-related quality of life, adherence to treatment, self-efficacy, pulmonary function, body mass index, and blood glucose values. Among the 85 eligible patients approached, 40 (47%) were enrolled and randomized to the intervention or control group; two patients subsequently withdrew consent. Retention rates after 5 and 10 coaching sessions were 67% and 50%, respectively. Reasons for stopping the intervention included lack of time, poor health, perceiving coaching as not helpful, lack of motivation, and no need for further coaching. Coaching was primarily face-to-face (68%). No significant differences were found between the groups on any of the secondary outcomes. Both telephone and face-to-face coaching were convenient for participants, with 50% receiving the maximum offered coaching sessions. However, the dropout rate early in the intervention was a concern. In future studies, eligible participants should be screened

  16. Addition of CF3 across unsaturated moieties: a powerful functionalization tool

    PubMed Central

    2014-01-01

    In the last few years, the efficient introduction of trifluoromethyl groups in organic molecules has become a major research focus. This review highlights the recent developments enabling the incorporation of CF3 groups across unsaturated moieties, preferentially alkenes, and the mechanistic scenarios governing these transformations. We have specially focused on methods involving the simultaneous formation of C–CF3 and C–C or C–heteroatom bonds by formal addition reactions across π-systems, as such difunctionalization processes hold valuable synthetic potential. PMID:24789472

  17. Preparation & characterization of SiO2 interface layer by dip coating technique on carbon fibre for Cf/SiC composites

    NASA Astrophysics Data System (ADS)

    Kumar, Kundan; Jariwala, C.; Pillai, R.; Chauhan, N.; Raole, P. M.

    2015-08-01

    Carbon fibres (Cf) are one of the most important reinforced materials for ceramic matrix composites such as Cf - SiC composites and they are generally sought for high temperature applications in as space application, nuclear reactor and automobile industries. But the major problem arise when Cf reinforced composites exposed to high temperature in an oxidizing environment, Cf react with oxygen and burnt away. In present work, we have studied the effect of silica (SiO2) coating as a protective coating on Cf for the Cf / SiC composites. The silica solution prepared by the sol-gel process and coating on Cf is done by dip coating technique with varying the withdrawing speed i.e. 2, 5, 8 mm/s with fixed dipping cycle (3 Nos.). The uniform silica coating on the Cf is shown by the Scanning Electron Microscope (SEM) analysis. The tensile test shows the increase in tensile strength with respect to increase in withdrawing speed. The isothermal oxidation analysis confirmed enhancement of oxidation resistance of silica coated Cf as compared tothe uncoated Cf.

  18. Satellite-like cells contribute to pax7-dependent skeletal muscle repair in adult zebrafish

    PubMed Central

    Berberoglu, Michael A.; Gallagher, Thomas L.; Morrow, Zachary T.; Talbot, Jared C.; Hromowyk, Kimberly J.; Tenente, Inês M.; Langenau, David M.; Amacher, Sharon L.

    2017-01-01

    Satellite cells, also known as muscle stem cells, are responsible for skeletal muscle growth and repair in mammals. Pax7 and Pax3 transcription factors are established satellite cell markers required for muscle development and regeneration, and there is great interest in identifying additional factors that regulate satellite cell proliferation, differentiation, and/or skeletal muscle regeneration. Due to the powerful regenerative capacity of many zebrafish tissues, even in adults, we are exploring the regenerative potential of adult zebrafish skeletal muscle. Here, we show that adult zebrafish skeletal muscle contains cells similar to mammalian satellite cells. Adult zebrafish satellite-like cells have dense heterochromatin, express Pax7 and Pax3, proliferate in response to injury, and show peak myogenic responses 4–5 days post-injury (dpi). Furthermore, using a pax7a-driven GFP reporter, we present evidence implicating satellite-like cells as a possible source of new muscle. In lieu of central nucleation, which distinguishes regenerating myofibers in mammals, we describe several characteristics that robustly identify newly-forming myofibers from surrounding fibers in injured adult zebrafish muscle. These characteristics include partially overlapping expression in satellite cells and regenerating myofibers of two RNA-binding proteins Rbfox2 and Rbfoxl1, known to regulate embryonic muscle development and function. Finally, by analyzing pax7a; pax7b double mutant zebrafish, we show that Pax7 is required for adult skeletal muscle repair, as it is in the mouse. PMID:28279710

  19. CD24-Positive Cells from Normal Adult Mouse Liver Are Hepatocyte Progenitor Cells

    PubMed Central

    Qiu, Qiong; Hernandez, Julio Cesar; Dean, Adam M.; Rao, Pulivarthi H.

    2011-01-01

    The identification of specific cell surface markers that can be used to isolate liver progenitor cells will greatly facilitate experimentation to determine the role of these cells in liver regeneration and their potential for therapeutic transplantation. Previously, the cell surface marker, CD24, was observed to be expressed on undifferentiated bipotential mouse embryonic liver stem cells and 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced oval cells. Here, we describe the isolation and characterization of a rare, primary, nonhematopoietic, CD24+ progenitor cell population from normal, untreated mouse liver. By immunohistochemistry, CD24-expressing cells in normal adult mouse liver were colocalized with CK19-positive cholangiocytes. This nonhematopoietic (CD45−, Ter119−) CD24+ cell population isolated by flow cytometry represented 0.04% of liver cells and expressed several markers of liver progenitor/oval cells. The immunophenotype of nonhematopoietic CD24+ cells was CD133, Dlk, and Sca-1 high, but c-Kit, Thy-1, and CD34 low. The CD24+ cells had increased expression of CK19, epithelial cell adhesion molecule, Sox 9, and FN14 compared with the unsorted cells. Upon transplantation of nonhematopoietic CD24+ cells under the sub-capsule of the livers of Fah knockout mice, cells differentiated into mature functional hepatocytes. Analysis of X and Y chromosome complements were used to determine whether or not fusion of the engrafted cells with the recipient hepatocytes occurred. No cells were found that contained XXXY or any other combination of donor and host sex chromosomes as would be expected if cell fusion had occurred. These results suggested that CD24 can be used as a cell surface marker for isolation of hepatocyte progenitor cells from normal adult liver that are able to differentiate into hepatocytes. PMID:21361791

  20. CD24-positive cells from normal adult mouse liver are hepatocyte progenitor cells.

    PubMed

    Qiu, Qiong; Hernandez, Julio Cesar; Dean, Adam M; Rao, Pulivarthi H; Darlington, Gretchen J

    2011-12-01

    The identification of specific cell surface markers that can be used to isolate liver progenitor cells will greatly facilitate experimentation to determine the role of these cells in liver regeneration and their potential for therapeutic transplantation. Previously, the cell surface marker, CD24, was observed to be expressed on undifferentiated bipotential mouse embryonic liver stem cells and 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced oval cells. Here, we describe the isolation and characterization of a rare, primary, nonhematopoietic, CD24+ progenitor cell population from normal, untreated mouse liver. By immunohistochemistry, CD24-expressing cells in normal adult mouse liver were colocalized with CK19-positive cholangiocytes. This nonhematopoietic (CD45-, Ter119-) CD24+ cell population isolated by flow cytometry represented 0.04% of liver cells and expressed several markers of liver progenitor/oval cells. The immunophenotype of nonhematopoietic CD24+ cells was CD133, Dlk, and Sca-1 high, but c-Kit, Thy-1, and CD34 low. The CD24+ cells had increased expression of CK19, epithelial cell adhesion molecule, Sox 9, and FN14 compared with the unsorted cells. Upon transplantation of nonhematopoietic CD24+ cells under the sub-capsule of the livers of Fah knockout mice, cells differentiated into mature functional hepatocytes. Analysis of X and Y chromosome complements were used to determine whether or not fusion of the engrafted cells with the recipient hepatocytes occurred. No cells were found that contained XXXY or any other combination of donor and host sex chromosomes as would be expected if cell fusion had occurred. These results suggested that CD24 can be used as a cell surface marker for isolation of hepatocyte progenitor cells from normal adult liver that are able to differentiate into hepatocytes.

  1. Conversion of adult endothelium to immunocompetent haematopoietic stem cells.

    PubMed

    Lis, Raphael; Karrasch, Charles C; Poulos, Michael G; Kunar, Balvir; Redmond, David; Duran, Jose G Barcia; Badwe, Chaitanya R; Schachterle, William; Ginsberg, Michael; Xiang, Jenny; Tabrizi, Arash Rafii; Shido, Koji; Rosenwaks, Zev; Elemento, Olivier; Speck, Nancy A; Butler, Jason M; Scandura, Joseph M; Rafii, Shahin

    2017-05-25

    Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0-8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression. During the specification phase (days 8-20), RUNX1 + FGRS-transduced endothelial cells commit to a haematopoietic fate, yielding rEC-HSCs that no longer require FGRS expression. The vascular niche drives a robust self-renewal and expansion phase of rEC-HSCs (days 20-28). rEC-HSCs have a transcriptome and long-term self-renewal capacity similar to those of adult haematopoietic stem cells, and can be used for clonal engraftment and serial primary and secondary multi-lineage reconstitution, including antigen-dependent adaptive immune function. Inhibition of TGFβ and CXCR7 or activation of BMP and CXCR4 signalling enhanced generation of rEC-HSCs. Pluripotency-independent conversion of endothelial cells into autologous authentic engraftable haematopoietic stem cells could aid treatment of haematological disorders.

  2. Immunophenotypic analysis of adult patients with T-cell lymphoblastic lymphoma treated with hyper-CVAD.

    PubMed

    Kato, Harumi; Yamamoto, Kazuhito; Kodaira, Takeshi; Higuchi, Yusuke; Yamamoto, Hideyuki; Saito, Toko; Taji, Hirofumi; Yatabe, Yasushi; Nakamura, Shigeo; Kinoshita, Tomohiro

    2018-03-01

    Immunophenotype is an important prognostic factor for childhood and adult T-cell acute lymphoblastic leukemia. However, immunophenotypic data from adult patients with T-cell lymphoblastic lymphoma (T-LBL) are scarcely available. Subjects were unselected adult patients with T-LBL who were treated with intensive chemotherapy. Immunophenotyping of tumor cells was performed according to standard techniques. A total of eight patients with a median age of 31 years were analyzed who received hyper-CVAD treatment for LBL. Immunophenotypic analysis showed that the most common tumor type was cortical T-cell type [early T (n = 2), cortical T (n = 4), and medullary T (n = 2)]. Two patients diagnosed with early T-cell type had early disease progression. Assessment of T-cell differentiation stages in malignant T lymphoblasts would be important in choosing treatment strategies for adult patients with T-LBL.

  3. Adult pituitary stem cells: from pituitary plasticity to adenoma development.

    PubMed

    Florio, Tullio

    2011-01-01

    The pituitary needs high plasticity of the hormone-producing cell compartment to generate the continuously changing hormonal signals that govern the key physiological processes it is involved in, as well as homeostatic cell turnover. However, the underlying mechanisms are still poorly understood. It was proposed that adult stem cells direct the generation of newborn cells with a hormonal phenotype according to the physiological requirements. However, only in recent years adult pituitary stem cells have begun to be phenotypically characterized in several studies that identified multiple stem/progenitor cell candidates. Also considering the incompletely defined features of this cell subpopulation, some discrepancies among the different reports are clearly apparent and long-term self-renewal remains to be unequivocally demonstrated. Here, all the recently published evidence is analyzed, trying, when possible, to reconcile the results of the different studies. Finally, with the perspective of shedding light on pituitary tumorigenesis and the development of potentially new pharmacological approaches directed against these cells, very recent evidence on the presence of putative cancer stem cells in human pituitary adenomas is discussed. Copyright © 2011 S. Karger AG, Basel.

  4. Impact of Donor Arterial Partial Pressure of Oxygen on Outcomes After Lung Transplantation in Adult Cystic Fibrosis Recipients.

    PubMed

    Hayes, Don; Kopp, Benjamin T; Kirkby, Stephen E; Reynolds, Susan D; Mansour, Heidi M; Tobias, Joseph D; Tumin, Dmitry

    2016-08-01

    Donor PaO2 levels are used for assessing organs for lung transplantation (LTx), but survival implications of PaO2 levels in adult cystic fibrosis (CF) patients receiving LTx are unclear. UNOS registry data spanning 2005-2013 were used to test for associations of donor PaO2 with patient survival and bronchiolitis obliterans syndrome (BOS) in adult (age ≥ 18 years) first-time LTx recipients diagnosed with CF. The analysis included 1587 patients, of whom 1420 had complete data for multivariable Cox models. No statistically significant differences among donor PaO2 categories of ≤200, 201-300, 301-400, or >400 mmHg were found in univariate survival analysis (log-rank test p = 0.290). BOS onset did not significantly differ across donor PaO2 categories (Chi-square p = 0.480). Multivariable Cox models of patient survival supported the lack of difference across donor PaO2 categories. Interaction analysis found a modest difference in survival between the two top categories of donor PaO2 when examining patients with body mass index (BMI) in the lowest decile (≤16.5 kg/m(2)). Donor PaO2 was not associated with survival or BOS onset in adult CF patients undergoing LTx. Notwithstanding statistically significant interactions between donor PaO2 and BMI, there was no evidence of post-LTx survival risk associated with donor PaO2 below conventional thresholds in any subgroup of adults with CF.

  5. ACCESS: The Arizona-CfA-Catolica Exoplanet Spectroscopy Survey

    NASA Astrophysics Data System (ADS)

    Lopez-Morales, Mercedes; Apai, Daniel; Jordan, Andres; Espinoza, Nestor; Rackham, Benjamin; Fraine, Jonathan D.; Rodler, Florian; Lewis, Nikole; Fortney, Jonathan J.; Osip, David J.

    2014-06-01

    The Arizona-CfA-Catolica Exoplanet Spectroscopy Survey (ACCESS) is an international, multi-institutional consortium with members from the Harvard-Smithsonian CfA, the University of Arizona, Pontificia Universidad Catolica in Chile, MIT and UC Santa Cruz and the Carnegie Institution. ACCESS' goal is to observe about two dozen planets covering a wide range of mass, radius, atmospheric temperatures and energy irradiation levels, with two main scientific goals: 1) to obtain, for the first time, a uniform sample of visible transmission spectra of exoplanets, allowing the study of their atmospheric characteristics as a statistically significant sample, and 2) to mature the technique of ground-based observations of exoplanetary atmospheres for future observations of small planets. Here we describe ACCESS and its first science results.

  6. Experimental ion mobility measurements in Xe-CF4 mixtures

    NASA Astrophysics Data System (ADS)

    Cortez, A. F. V.; Kaja, M. A.; Escada, J.; Santos, M. A. G.; Veenhof, R.; Neves, P. N. B.; Santos, F. P.; Borges, F. I. G. M.; Conde, C. A. N.

    2018-04-01

    In this paper we present the results of the ion mobility measurements made in gaseous mixtures of xenon with carbon tetrafluoride (Xe-CF4) for pressures ranging from 6 to 10 Torr (8-10.6 mbar) and for low reduced electric fields in the 10 to 25 Td range (2.4-6.1 kVṡcm‑1ṡbar‑1), at room temperature. The time-of-arrival spectra revealed one or two peaks depending on the gas relative abundances, which were attributed to CF3+ and to Xe2+ ions. However, for Xe concentrations above 60%, only one peak remains (Xe2+). The reduced mobilities obtained from the peak centroid of the time-of-arrival spectra are presented for Xe concentrations in the 5%-95% range.

  7. Reserve stem cells: Reprogramming of differentiated cells fuels repair, metaplasia, and neoplasia in the adult gastrointestinal tract

    PubMed Central

    Mills, Jason C.; Sansom, Owen J.

    2016-01-01

    It has long been known that differentiated cells can switch fates, especially in vitro, but only recently has there been a critical mass of publications describing the mechanisms adult, post-mitotic cells use in vivo to reverse their differentiation state. We propose that this sort of cellular reprogramming is a fundamental cellular process akin to apoptosis or mitosis. Because reprogramming can invoke regenerative cells from mature cells, it is critical to the longterm maintenance of tissues like the pancreas, which encounter large insults during adulthood but lack constitutively active adult stem cells to repair the damage. However, even in tissues with adult stem cells, like stomach and intestine, reprogramming may allow mature cells to serve as reserve (“quiescent”) stem cells when normal stem cells are compromised. We propose that the potential downside to reprogramming is that it increases risk for cancers that occur late in adulthood. Mature, long-lived cells may have years of exposure to mutagens. Mutations that affect the physiological function of differentiated, post-mitotic cells may lead to apoptosis, but mutations in genes that govern proliferation might not be selected against. Hence, reprogramming with reentry into the cell cycle might unmask those mutations, causing an irreversible progenitor-like, proliferative state. We review recent evidence showing that reprogramming fuels irreversible metaplastic and precancerous proliferations in stomach and pancreas. Finally, we illustrate how we think reprogrammed differentiated cells are likely candidates as cells of origin for cancers of the intestine. PMID:26175494

  8. Designing a SCAR molecular marker for monitoring Trichoderma cf. harzianum in experimental communities.

    PubMed

    Pérez, Gabriel; Verdejo, Valentina; Gondim-Porto, Clarissa; Orlando, Julieta; Carú, Margarita

    2014-11-01

    Several species of the fungal genus Trichoderma establish biological interactions with various micro- and macro-organisms. Some of these interactions are relevant in ecological terms and in biotechnological applications, such as biocontrol, where Trichoderma could be considered as an invasive species that colonizes a recipient community. The success of this invasion depends on multiple factors, which can be assayed using experimental communities as study models. Therefore, the aim of this work is to develop a species-specific sequence-characterized amplified region (SCAR) marker to monitor the colonization and growth of T. cf. harzianum when it invades experimental communities. For this study, 16 randomly amplified polymorphic DNA (RAPD) primers of 10-mer were used to generate polymorphic patterns, one of which generated a band present only in strains of T. cf. harzianum. This band was cloned, sequenced, and five primers of 20-23 mer were designed. Primer pairs 2F2/2R2 and 2F2/2R3 successfully and specifically amplified fragments of 278 and 448 bp from the T. cf. harzianum BpT10a strain DNA, respectively. Both primer pairs were also tested against the DNA from 14 strains of T. cf. harzianum and several strains of different fungal genera as specificity controls. Only the DNA from the strains of T. cf. harzianum was successfully amplified. Moreover, primer pair 2F2/2R2 was assessed by quantitative real-time polymerase chain reaction (PCR) using fungal DNA mixtures and DNA extracted from fungal experimental communities as templates. T. cf. harzianum was detectable even when as few as 100 copies of the SCAR marker were available or even when its population represented only 0.1% of the whole community.

  9. Designing a SCAR molecular marker for monitoring Trichoderma cf. harzianum in experimental communities* #

    PubMed Central

    Pérez, Gabriel; Verdejo, Valentina; Gondim-Porto, Clarissa; Orlando, Julieta; Carú, Margarita

    2014-01-01

    Several species of the fungal genus Trichoderma establish biological interactions with various micro- and macro-organisms. Some of these interactions are relevant in ecological terms and in biotechnological applications, such as biocontrol, where Trichoderma could be considered as an invasive species that colonizes a recipient community. The success of this invasion depends on multiple factors, which can be assayed using experimental communities as study models. Therefore, the aim of this work is to develop a species-specific sequence-characterized amplified region (SCAR) marker to monitor the colonization and growth of T. cf. harzianum when it invades experimental communities. For this study, 16 randomly amplified polymorphic DNA (RAPD) primers of 10-mer were used to generate polymorphic patterns, one of which generated a band present only in strains of T. cf. harzianum. This band was cloned, sequenced, and five primers of 20–23 mer were designed. Primer pairs 2F2/2R2 and 2F2/2R3 successfully and specifically amplified fragments of 278 and 448 bp from the T. cf. harzianum BpT10a strain DNA, respectively. Both primer pairs were also tested against the DNA from 14 strains of T. cf. harzianum and several strains of different fungal genera as specificity controls. Only the DNA from the strains of T. cf. harzianum was successfully amplified. Moreover, primer pair 2F2/2R2 was assessed by quantitative real-time polymerase chain reaction (PCR) using fungal DNA mixtures and DNA extracted from fungal experimental communities as templates. T. cf. harzianum was detectable even when as few as 100 copies of the SCAR marker were available or even when its population represented only 0.1% of the whole community. PMID:25367789

  10. Adipose-derived adult stem cells: available technologies for potential clinical regenerative applications in dentistry.

    PubMed

    Catalano, Enrico; Cochis, Andrea; Varoni, Elena; Rimondini, Lia; Carrassi, Antonio; Azzimonti, Barbara

    2013-01-01

    Tissue homeostasis depends closely on the activity and welfare of adult stem cells. These cells represent a promising tool for biomedical research since they can aid in treatment and promote the regeneration of damaged organs in many human disorders. Adult stem cells indefinitely preserve their ability to self-renew and differentiate into various phenotypes; this capacity could be promoted in vitro by particular culture conditions (differentiation media) or spontaneously induced in vivo by exploiting the biochemical and mechanical properties of the tissue in which the stem cells are implanted. Among the different sources of adult stem cells, adipose tissue is an attractive possibility thanks to its ready availability and the standard extraction techniques at our disposal today. This review discusses the isolation, characterization, and differentiation of human adipose-derived adult stem cells, as well as regeneration strategies, therapeutic uses, and adverse effects of their delivery. In particular, since oral disorders (e.g., trauma, erosion, and chronic periodontitis) often cause the loss of dental tissue along with functional, phonetic, and aesthetic impairment, this review focuses on the application of human adipose-derived adult stem cells, alone or in combination with biomaterials, in treating oral diseases.

  11. HPV-Induced Field Cancerisation: Transformation of Adult Tissue Stem Cell Into Cancer Stem Cell.

    PubMed

    Olivero, Carlotta; Lanfredini, Simone; Borgogna, Cinzia; Gariglio, Marisa; Patel, Girish K

    2018-01-01

    Field cancerisation was originally described as a basis for multiple head and neck squamous cell carcinoma (HNSCC) and is a pre-malignant phenomenon that is frequently attributable to oncogenic human papillomavirus (HPV) infection. Our work on β-HPV-induced cutaneous squamous cell carcinomas identified a novel Lrig1+ hair follicle junctional zone keratinocyte stem cell population as the basis for field cancerisation. Herein, we describe the ability for HPV to infect adult tissue stem cells in order to establish persistent infection and induce their proliferation and displacement resulting in field cancerisation. By review of the HPV literature, we reveal how this mechanism is conserved as the basis of field cancerisation across many tissues. New insights have identified the capacity for HPV early region genes to dysregulate adult tissue stem cell self-renewal pathways ensuring that the expanded population preserve its stem cell characteristics beyond the stem cell niche. HPV-infected cells acquire additional transforming mutations that can give rise to intraepithelial neoplasia (IEN), from environmental factors such as sunlight or tobacco induced mutations in skin and oral cavity, respectively. With establishment of IEN, HPV viral replication is sacrificed with loss of the episome, and the tissue is predisposed to multiple cancer stem cell-driven carcinomas.

  12. Surface modified CF x cathode material for ultrafast discharge and high energy density

    DOE PAGES

    Dai, Yang; Zhu, Yimei; Cai, Sendan; ...

    2014-11-10

    Li/CF x primary possesses the highest energy density of 2180 W h kg⁻¹ among all primary lithium batteries. However, a key limitation for the utility of this type of battery is in its poor rate capability because the cathode material, CF x, is an intrinsically poor electronic conductor. Here, we report on our development of a controlled process of surface de-fluorination under mild hydrothermal conditions to modify the highly fluorinated CF x. The modified CF x, consisting of an in situ generated shell component of F-graphene layers, possesses good electronic conductivity and removes the transporting barrier for lithium ions, yieldingmore » a high-capacity performance and an excellent rate-capability. Indeed, a capacity of 500 mA h g⁻¹ and a maximum power density of 44 800 W kg⁻¹ can be realized at the ultrafast rate of 30 C (24 A g⁻¹), which is over one order of magnitude higher than that of the state-of-the-art primary lithium-ion batteries.« less

  13. Identification, Characterization, and Utilization of Adult Meniscal Progenitor Cells

    DTIC Science & Technology

    2016-09-01

    development of knee osteoarthritis (OA). New treatments centered on the stem/progenitor cell population resident within the adult meniscus will be key to...cells, progenitor cells, meniscus healing, meniscus repair, osteoarthritis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER...common underlying cause of post- traumatic osteoarthritis . This is particularly striking in young, healthy individuals such as military personnel

  14. Origins of adult pigmentation: diversity in pigment stem cell lineages and implications for pattern evolution

    PubMed Central

    Spiewak, Jessica E.

    2014-01-01

    Summary Teleosts comprise about half of all vertebrate species and exhibit an extraordinary diversity of adult pigment patterns that function in shoaling, camouflage and mate choice and have played important roles in speciation. Here, we review recent studies that have identified several distinct neural crest lineages, with distinct genetic requirements, that give rise to adult pigment cells in fishes. These lineages include post-embryonic, peripheral nerve associated stem cells that generate black melanophores and iridescent iridophores, cells derived directly from embryonic neural crest cells that generate yellow-orange xanthophores, and bipotent stem cells that generate both melanophores and xanthophores. This complexity in adult chromatophore lineages has implications for our understanding of adult traits, melanoma, and the evolutionary diversification of pigment cell lineages and patterns. PMID:25421288

  15. Pre-flight evaluation of adult patients with cystic fibrosis: a cross-sectional study.

    PubMed

    Edvardsen, Elisabeth; Akerø, Aina; Skjønsberg, Ole Henning; Skrede, Bjørn

    2017-02-06

    Air travel may imply a health hazard for patients with cystic fibrosis (CF) due to hypobaric environment in the aircraft cabin. The objective was to identify pre-flight variables, which might predict severe hypoxaemia in adult CF patients during air travel. Thirty adult CF-patients underwent pre-flight evaluation with spirometry, arterial oxygen tension (PaO 2 ), pulse oximetry (SpO 2 ) and cardiopulmonary exercise testing (CPET) at sea level (SL). The results were related to the PaO 2 obtained during a hypoxia-altitude simulation test (HAST) in which a cabin altitude of 2438 m (8000 ft) was simulated by breathing 15.1% oxygen. Four patients fulfilled the criteria for supplemental oxygen during air travel (PaO 2 HAST  < 6.6 kPa). While walking slowly during HAST, another eleven patients dropped below PaO 2 HAST 6.6 kPa. Variables obtained during CPET (PaO 2 CPET , SpO 2 CPET , minute ventilation/carbon dioxide output, maximal oxygen uptake) showed the strongest correlation to PaO 2 HAST . Exercise testing might be of value for predicting in-flight hypoxaemia and thus the need for supplemental oxygen during air travel in CF patients. Trial registration The study is retrospectively listed in the ClinicalTrials.gov Protocol Registration System: NCT01569880 (date; 30/3/2012).

  16. Regulatory System for Stem/Progenitor Cell Niches in the Adult Rodent Pituitary

    PubMed Central

    Yoshida, Saishu; Kato, Takako; Kato, Yukio

    2016-01-01

    The anterior lobe of the pituitary gland is a master endocrine tissue composed of five types of endocrine cells. Although the turnover rate of pituitary endocrine cells is as low as about 1.6% per day, recent studies have demonstrated that Sex-determining region Y-box 2 (SOX2)+-cells exist as pituitary stem/progenitor cells in the adult anterior lobe and contribute to cell regeneration. Notably, SOX2+-pituitary stem/progenitor cells form two types of niches in this tissue: the marginal cell layer (MCL-niche) and the dense cell clusters scattering in the parenchyma (parenchymal-niche). However, little is known about the mechanisms and factors for regulating the pituitary stem/progenitor cell niches, as well as the functional differences between the two types of niches. Elucidation of the regulatory mechanisms in the niches might enable us to understand the cell regeneration system that acts in accordance with physiological demands in the adult pituitary. In this review, so as to reveal the regulatory mechanisms of the two types of niche, we summarize the regulatory factors and their roles in the adult rodent pituitary niches by focusing on three components: soluble factors, cell surface proteins and extracellular matrixes. PMID:26761002

  17. VizieR Online Data Catalog: SNe II light curves & spectra from the CfA (Hicken+, 2017)

    NASA Astrophysics Data System (ADS)

    Hicken, M.; Friedman, A. S.; Blondin, S.; Challis, P.; Berlind, P.; Calkins, M.; Esquerdo, G.; Matheson, T.; Modjaz, M.; Rest, A.; Kirshner, R. P.

    2018-01-01

    Since all of the optical photometry reported here was produced as part of the CfA3 and CfA4 processing campaigns, see Hicken+ (2009, J/ApJ/700/331) and Hicken+ (2012, J/ApJS/200/12) for greater details on the instruments, observations, photometry pipeline, calibration, and host-galaxy subtraction used to create the CfA SN II light curves. (8 data files).

  18. Enhanced IL-1{beta}-induced IL-8 production in cystic fibrosis lung epithelial cells is dependent of both mitogen-activated protein kinases and NF-{kappa}B signaling

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

    Muselet-Charlier, Celine; Universite Pierre et Marie Curie-Paris 6, Paris, UMR-S719, F-75012; Roque, Telma

    2007-06-01

    Transcription nuclear factor-{kappa}B (NF-{kappa}B) is hyperactivated in cystic fibrosis (CF) lung epithelial cells, and participates in exaggerated IL-8 production in the CF lung. We recently found that rapid activation of NF-{kappa}B occurred in a CF lung epithelial IB3-1 cell line (CF cells) upon IL-1{beta} stimulation, which was not observed in its CFTR-corrected lung epithelial S9 cell line (corrected cells). To test whether other signaling pathways such as that of mitogen-activated protein kinases (MAPKs) could be involved in IL-1{beta}-induced IL-8 production of CF cells, we investigated ERK1/2, JNK, and p38MAP signaling compared to NF-{kappa}B. Within 30 min, exposure to IL-1{beta} causedmore » high activation of NF-{kappa}B, ERK1/2, p38MAP but not JNK in CF cells compared to corrected cells. Treatment of IL-1{beta}-stimulated CF cells with a series of chemical inhibitors of NF-{kappa}B, ERK1/2, and p38MAP, when used separately, reduced slightly IL-8 production. However, when used together, these inhibitors caused a blockade in IL-1{beta}-induced IL-8 production in CF cells. Understanding of the cross-talk between NF-{kappa}B and MAPKs signaling in CF lung epithelial cells may help in developing new therapeutics to reduce lung inflammation in patients with CF.« less

  19. Adult bone marrow-derived stem cells for organ regeneration and repair.

    PubMed

    Tögel, Florian; Westenfelder, Christof

    2007-12-01

    Stem cells have been recognized as a potential tool for the development of innovative therapeutic strategies. There are in general two types of stem cells, embryonic and adult stem cells. While embryonic stem cell therapy has been riddled with problems of allogeneic rejection and ethical concerns, adult stem cells have long been used in the treatment of hematological malignancies. With the recognition of additional, potentially therapeutic characteristics, bone marrow-derived stem cells have become a tool in regenerative medicine. The bone marrow is an ideal source of stem cells because it is easily accessible and harbors two types of stem cells. Hematopoietic stem cells give rise to all blood cell types and have been shown to exhibit plasticity, while multipotent marrow stromal cells are the source of osteocytes, chondrocytes, and fat cells and have been shown to support and generate a large number of different cell types. This review describes the general characteristics of these stem cell populations and their current and potential future applications in regenerative medicine. 2007 Wiley-Liss, Inc

  20. A theoretical study on the mechanism and dynamics of reactions (CF3)2CHOCH2F/(CF3)2CHOCHF2 with OH radical

    NASA Astrophysics Data System (ADS)

    Wang, Chunzhang; Wen, Jinmiao; He, Hongqing; Wang, Li

    2014-11-01

    The information related with the mechanism of reactions (CF3)2CHOCH2F + OH (R1) and (CF3)2CHOCHF2 + OH (R2) was explored theoretically at the BMC-CCSD//BMK/6-311 + G(d,p) level. Based on the optimised structures, energies, and other information, the rate constants were evaluated by the canonical variational transition-state theory with small curvature tunneling contributions in a temperature range of 220-2000 K. For each reaction, there are both hydrogen-abstraction and displacement channels. In addition, more than one hydrogen atom can be abstracted. The relationship between hydrogen abstraction and displacement, between different hydrogen-abstraction channels, and between reactions R1 and R2 are elucidated.

  1. Pediatric to Adult Care Transition: Perspectives of Young Adults With Sickle Cell Disease.

    PubMed

    Porter, Jerlym S; Wesley, Kimberly M; Zhao, Mimi S; Rupff, Rebecca J; Hankins, Jane S

    2017-10-01

    The aim of this study was to explore perspectives of transition and transition readiness of young adult patients (YAs) with sickle cell disease (SCD) who have transitioned to adult health care. In all, 19 YAs with SCD (ages 18-30 years) participated in one of three focus groups and completed a brief questionnaire about transition topics. Transcripts were coded and emergent themes were examined using the social-ecological model of adolescent and young adult readiness for transition (SMART). Themes were consistent with most SMART components. Adult provider relationships and negative medical experiences emerged as salient factors. YAs ranked choosing an adult provider, seeking emergency care, understanding medications/medication adherence, knowing SCD complications, and being aware of the impact of health behaviors as the most important topics to include in transition programming. The unique perspectives of YAs can inform the development and evaluation of SCD transition programming by incorporating the identified themes. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  2. Comprehensive vacuum ultraviolet photoionization study of the CF3• trifluoromethyl radical using synchrotron radiation

    NASA Astrophysics Data System (ADS)

    Dossmann (Soldi-Lose), Héloïse; Garcia, Gustavo A.; Nahon, Laurent; de Miranda, Barbara K. C.; Alcaraz, Christian

    2012-05-01

    The trifluoromethyl radical, CF3•, is studied for the first time by means of threshold photoelectron spectroscopy (TPES). The radical is produced in the gas phase using the flash-pyrolysis technique from hexafluoroethane as a precursor. CF3+ total ion yield and mass-selected TPES of the radical are recorded using a spectrometer based upon velocity map imaging and Wiley-McLaren time-of-flight coupled to the synchrotron radiation. The high resolution of the instrument and of the photons allows the observation of rich vibrational progressions in the TPES of CF3•. By using Franck-Condon factors computed by Bowman and coworkers, we have been able to simulate the TPES. The initial vibrational temperature of the radical beam has been evaluated at 350 ± 70 K. The structures have been identified as transitions between (n1,n2) and (n1+,n2+) vibrational levels of CF3 and CF3+ with small excitation of the breathing mode, ν1+, and large excitation (n2+ = 10-26) of the umbrella mode, ν2+, in the cation. From the energy separation between the two resolved peaks of each band, a value of 994 ± 16 cm-1 has been derived for the ν1+ breathing frequency of CF3+. For the high-lying n2+ levels, the apparent ν2+ umbrella spacing, 820 ± 14 cm-1, is fairly constant. Taking into account the ν2+ anharmonicity calculated by Bowman and coworkers, we have deduced ν2+ = 809 ± 14 cm-1, and semi-empirical estimations of the adiabatic ionization energy IEad.(CF3•) are proposed in good agreement with most of previous works. A value of the vertical ionization potential, IEvert.(CF3•) = 11.02 eV, has been derived from the observation of a photoelectron spectrum recorded at a fixed photon energy of 12 eV.

  3. T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation.

    PubMed

    Vago, Luca; Oliveira, Giacomo; Bondanza, Attilio; Noviello, Maddalena; Soldati, Corrado; Ghio, Domenico; Brigida, Immacolata; Greco, Raffaella; Lupo Stanghellini, Maria Teresa; Peccatori, Jacopo; Fracchia, Sergio; Del Fiacco, Matteo; Traversari, Catia; Aiuti, Alessandro; Del Maschio, Alessandro; Bordignon, Claudio; Ciceri, Fabio; Bonini, Chiara

    2012-08-30

    The genetic modification of T cells with a suicide gene grants a mechanism of control of adverse reactions, allowing safe infusion after partially incompatible hematopoietic stem cell transplantation (HSCT). In the TK007 clinical trial, 22 adults with hematologic malignancies experienced a rapid and sustained immune recovery after T cell-depleted HSCT and serial infusions of purified donor T cells expressing the HSV thymidine kinase suicide gene (TK+ cells). After a first wave of circulating TK+ cells, the majority of T cells supporting long-term immune reconstitution did not carry the suicide gene and displayed high numbers of naive lymphocytes, suggesting the thymus-dependent development of T cells, occurring only upon TK+ -cell engraftment. Accordingly, after the infusions, we documented an increase in circulating TCR excision circles and CD31+ recent thymic emigrants and a substantial expansion of the active thymic tissue as shown by chest tomography scans. Interestingly, a peak in the serum level of IL-7 was observed after each infusion of TK+ cells, anticipating the appearance of newly generated T cells. The results of the present study show that the infusion of genetically modified donor T cells after HSCT can drive the recovery of thymic activity in adults, leading to immune reconstitution.

  4. Central Artery Stiffness, Baroreflex Sensitivity, and Brain White Matter Neuronal Fiber Integrity in Older Adults

    PubMed Central

    Tarumi, Takashi; de Jong, Daan L.K.; Zhu, David C.; Tseng, Benjamin Y.; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B.; Kerwin, Diana R.; Lu, Hanzhang; Cullum, C. Munro; Zhang, Rong

    2015-01-01

    Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65±6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults. PMID:25623500

  5. Relationship between physical activity and cognitive function in apparently healthy young to middle-aged adults: A systematic review.

    PubMed

    Cox, Eka Peng; O'Dwyer, Nicholas; Cook, Rebecca; Vetter, Melanie; Cheng, Hoi Lun; Rooney, Kieron; O'Connor, Helen

    2016-08-01

    There is increasing evidence that physical activity (PA) positively affects cognitive function (CF). Existing research has focussed on this association in children and the elderly, with less research available in young to middle-aged adults who constitute a substantial proportion of the population. A systematic review investigating the relationship between habitual PA (≥12 months) and CF in young to middle-aged adults (18-50 years). A search was conducted using AMED, CINAHL, MEDLINE, PsychINFO, AUSPORT MED and SPORTDiscus databases. Eligible studies had to report descriptive statistics for CF and PA levels in healthy participants 18-50 years. Effect sizes (ES) (Hedges g) were calculated where possible. The initial search netted 26,988 potentially relevant manuscripts, with four more identified through hand searching. Fourteen were included for review. A range of validated platforms assessed CF across three domains: executive function (12 studies), memory (four studies) and processing speed (seven studies). Habitual PA was assessed via questionnaire/self-report methods (n=13, 8 validated) or accelerometers (n=1). In studies of executive function, five found a significant ES in favour of higher PA, ranging from small to large. Although three of four studies in the memory domain reported a significant benefit of higher PA, there was only one significant ES, which favoured low PA. Only one study examining processing speed had a significant ES, favouring higher PA. A limited body of evidence supports a positive effect of PA on CF in young to middle-aged adults. Further research into this relationship at this age stage is warranted. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  6. Creep and Oxidation Behavior of Modified CF8C-Plus with W, Cu, Ni, and Cr

    NASA Astrophysics Data System (ADS)

    Unocic, Kinga A.; Dryepondt, Sebastien; Yamamoto, Yukinori; Maziasz, Philip J.

    2016-04-01

    The microstructures of modified CF8C-Plus (Fe-19Cr-12Ni-0.4W-3.8Mn-0.2Mo-0.6Nb-0.5Si-0.9C) with W and Cu (CF8CPWCu) and CF8CPWCu enhanced with 21Cr + 15Ni or 22Cr + 17.5Ni were characterized in the as-cast condition and after creep testing. When imaged at lower magnifications, the as-cast microstructure was similar among all three alloys as they all contained a Nb-rich interdendritic phase and Mn-based inclusions. Transmission electron microscopy (TEM) analysis showed the presence of nanoscale Cu-rich nanoprecipitates distributed uniformly throughout the matrix of CF8CPWCu, whereas in CF8CPWCu22/17, Cu precipitates were found primarily at the grain boundaries. The presence of these nanoscale Cu-rich particles, in addition to W-rich Cr23C6, nanoscale Nb carbides, and Z-phase (Nb2Cr2N2), improved the creep strength of the CF8CPWCu steel. Modification of CF8CPWCu with Cr and Ni contents slightly decreased the creep strength but significantly improved the oxidation behavior at 1073 K (800 °C). In particular, the addition of 22Cr and 17.5Ni strongly enhanced the oxidation resistance of the stainless steel resulting in a 100 degrees or greater temperature improvement, and this composition provided the best balance between improving both mechanical properties and oxidation resistance.

  7. Creep and oxidation behavior of modified CF8C-plus with W, Cu, Ni, and Cr

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

    Unocic, Kinga A.; Dryepondt, Sebastien N.; Yamamoto, Yukinori

    Here, the microstructures of modified CF8C-Plus (Fe-19Cr-12Ni-0.4W-3.8Mn-0.2Mo-0.6Nb-0.5Si-0.9C) with W and Cu (CF8CPWCu) and CF8CPWCu enhanced with 21Cr + 15Ni or 22Cr + 17.5Ni were characterized in the as-cast condition and after creep testing. When imaged at lower magnifications, the as-cast microstructure was similar among all three alloys as they all contained a Nb-rich interdendritic phase and Mn-based inclusions. Transmission electron microscopy (TEM) analysis showed the presence of nanoscale Cu-rich nanoprecipitates distributed uniformly throughout the matrix of CF8CPWCu, whereas in CF8CPWCu22/17, Cu precipitates were found primarily at the grain boundaries. The presence of these nanoscale Cu-rich particles, in addition to W-richmore » Cr 23C 6, nanoscale Nb carbides, and Z-phase (Nb 2Cr 2N 2), improved the creep strength of the CF8CPWCu steel. Modification of CF8CPWCu with Cr and Ni contents slightly decreased the creep strength but significantly improved the oxidation behavior at 1073 K (800 °C). In particular, the addition of 22Cr and 17.5Ni strongly enhanced the oxidation resistance of the stainless steel resulting in a 100 degrees or greater temperature improvement, and this composition provided the best balance between improving both mechanical properties and oxidation resistance.« less

  8. Creep and oxidation behavior of modified CF8C-plus with W, Cu, Ni, and Cr

    DOE PAGES

    Unocic, Kinga A.; Dryepondt, Sebastien N.; Yamamoto, Yukinori; ...

    2016-02-01

    Here, the microstructures of modified CF8C-Plus (Fe-19Cr-12Ni-0.4W-3.8Mn-0.2Mo-0.6Nb-0.5Si-0.9C) with W and Cu (CF8CPWCu) and CF8CPWCu enhanced with 21Cr + 15Ni or 22Cr + 17.5Ni were characterized in the as-cast condition and after creep testing. When imaged at lower magnifications, the as-cast microstructure was similar among all three alloys as they all contained a Nb-rich interdendritic phase and Mn-based inclusions. Transmission electron microscopy (TEM) analysis showed the presence of nanoscale Cu-rich nanoprecipitates distributed uniformly throughout the matrix of CF8CPWCu, whereas in CF8CPWCu22/17, Cu precipitates were found primarily at the grain boundaries. The presence of these nanoscale Cu-rich particles, in addition to W-richmore » Cr 23C 6, nanoscale Nb carbides, and Z-phase (Nb 2Cr 2N 2), improved the creep strength of the CF8CPWCu steel. Modification of CF8CPWCu with Cr and Ni contents slightly decreased the creep strength but significantly improved the oxidation behavior at 1073 K (800 °C). In particular, the addition of 22Cr and 17.5Ni strongly enhanced the oxidation resistance of the stainless steel resulting in a 100 degrees or greater temperature improvement, and this composition provided the best balance between improving both mechanical properties and oxidation resistance.« less

  9. Trajectories of caregiver burden in families of adult cystic fibrosis patients.

    PubMed

    Wojtaszczyk, Ann; Glajchen, Myra; Portenoy, Russell K; Berdella, Maria; Walker, Patricia; Barrett, Malcolm; Chen, Jack; Plachta, Amy; Balzano, Julie; Fresenius, Ashley; Wilder, Kenya; Langfelder-Schwind, Elinor; Dhingra, Lara

    2017-10-17

    Little is known about the experience of family caregivers of adults with cystic fibrosis (CF). This information is important for the identification of caregivers at risk for burden. This was a longitudinal analysis of survey data obtained from caregivers of adult CF patients participating in an early intervention palliative care trial. Caregivers completed the validated Brief Assessment Scale for Caregivers (BASC) repeatedly over a 28-month period. Mixed-effects modeling evaluated multivariate associations with positive and negative caregiver perceptions over time. Of the 54 caregivers, 47.9% were spouses. The mean age was 50.9 years (SD = 13.2); 72.2% were women; 75.9% were married; and 63.0% were employed. At baseline, the BASC revealed large variations in positive and negative perceptions of caregiving. Although average scores over time were unchanging, variation was greater across caregivers than within caregivers (0.49 vs. 0.27, respectively). At baseline, the positive impact of caregiving in the sample was higher than the negative impact. Multivariate analysis revealed that patients' baseline pulmonary function and their full-time employment status predicted caregiver burden over time. Caregivers of CF patients varied in their positive and negative caregiving experiences, although burden levels in individual caregivers were stable over time. When the disease was advanced, caregivers of CF patients experienced more overall burden but also more positive impact. This suggests that the role of caregivers may become more meaningful as disease severity worsens. In addition, full-time patient employment was associated with lower caregiver burden regardless of disease severity. This suggests that burden in CF caregivers may be predicted by financial strain or benefits conferred by patient employment. These associations require further investigation to determine whether highly burdened caregivers can be identified and assisted using tailored interventions.

  10. Treatment of Dry Eye Syndrome with Orally Administered CF101: Data from a Phase 2 Clinical Trial

    PubMed Central

    Avni, Isaac; Garzozi, Hanna J.; Barequet, Irina S.; Segev, Fanni; Varssano, David; Sartani, Gil; Chetrit, Noa; Bakshi, Erez; Zadok, David; Tomkins, Oren; Litvin, Gilad; Jacobson, Kenneth A.; Fishman, Sari; Harpaz, Zivit; Farbstein, Motti; Bar Yehuda, Sara; Silverman, Michael H.; Kerns, William D.; Bristol, David R.; Cohn, Ilan; Fishman, Pnina

    2013-01-01

    Objective To explore the safety and efficacy of CF101, an A3 adenosine receptor agonist, in patients with moderate-to-severe dry eye syndrome Design Phase 2, multicenter, randomized, double-masked, placebo-controlled, parallel-group study. Participants 68 patients completed the study, 35 patients in the placebo group and 33 patients in the CF101 group. Intervention Patients were orally treated with either 1 mg CF101 pills or matching vehicle-filled placebo pills, given twice daily for 12 weeks, followed by a 2-week post-treatment observation. Main Outcome Measures Efficacy an improvement of >25% over baseline at week 12 in one of the following parameters: (a) tear break-up time (BUT); (b) superficial punctate keratitis assessed by fluorescein staining (FS); (c) Schirmer tear test 1 (ST1). Safety clinical laboratory safety tests, ophthalmic examinations, intraocular pressure (IOP) measurements, electrocardiographic evaluations, vital sign measurements and monitoring of adverse events. Results A statistically significant increase in the proportion of patients who achieved more than 25% improvement in the corneal staining and in the clearance of corneal staining was noted between the CF101-treated group and the placebo group. Treatment with CF101 resulted in a statistically significant improvement in the mean change from baseline at week 12 of the corneal staining, BUT, and tear meniscus (TM) height in the CF101-treated group CF101 was well tolerated and exhibited an excellent safety profile with no serious adverse events. A statistically significant decrease from baseline was observed in the IOP of the CF101-treated group in comparison with the placebo group. Conclusions CF101, given orally, induced a statistically significant improvement in the corneal staining and an improvement in the BUT and TM in patients with moderate-to-severe dry eye syndrome. The drug was very well tolerated. These data and the anti-inflammatory characteristic of CF101 support further study

  11. Mechanistic study on the fluorination of K[B(CN)4] with ClF enabling the high yield and large scale synthesis of K[B(CF3)4] and K[(CF3)3BCN].

    PubMed

    Bernhardt, Eduard; Finze, Maik; Willner, Helge

    2011-10-17

    The fluorination of K[B(CN)(4)] with ClF is studied by millimolar test reactions in aHF and CH(2)Cl(2) solution and by subsequent identification of intermediates such as B-CF═NCl, B-CF(2)-NCl(2), and B-CF(3) species as well as NCl(3) by (19)F, (11)B NMR, and Raman spectroscopy, respectively. At first one cyano group of K[B(CN)(4)] is converted fast into a CF(3) group, and with increasing fluorination the reaction becomes slower and several intermediates could be observed. On the basis of these results, a synthesis was developed for K[B(CF(3))(4)] on a 0.2 molar scale by treatment of K[B(CN)(4)] diluted in aHF with ClF. The course of the reactions was followed by (i) monitoring the vapor pressure inside the reactor, (ii) observing the heat dissipation during ClF uptake, and (iii) measuring the volume of the released nitrogen gas. Since the fluorination of the last cyano group proceeds very slowly, the selective synthesis of K[(CF(3))(3)BCN] on a 0.2 molar scale is possible, as well. The analysis of the mechanisms, thermodynamics, and kinetics of the fluorination reactions is supported by density functional theory (DFT) calculations.

  12. A prospective analysis of unplanned patient-initiated contacts in an adult cystic fibrosis centre.

    PubMed

    Burnet, Espérie; Hubert, Dominique; Champreux, Juliette; Honoré, Isabelle; Kanaan, Reem; Panzo, Rosewilta; Burgel, Pierre-Régis

    2018-05-07

    Timely response should be provided when patients contact the cystic fibrosis (CF) centre in between scheduled visits. Little data exist on unplanned patient-initiated contacts in CF adults. A two-stage prospective study was undertaken from 1 January to 31 December 2015 at Cochin Hospital, Paris (France). The first stage included all adults (≥18 years) who initiated unplanned contacts to the CF centre over four months. Four physicians and three nurses systematically recorded unplanned patient-initiated contacts. The data was analysed to determine why and how patients contacted the CF centre and time spent responding to their request(s). The second stage (one physician, three nurses) lasted twelve months and explored whether high contact frequency was associated with disease severity, using multivariate logistic regression. In the first stage, 259 of 410 patients (63%) initiated at least one unplanned contact, corresponding to 1067 contacts over 4 months. Patients favoured email with physicians (61% of contacts) and telephone with nurses (87% of contacts). Total time spent by the 7 caregivers on providing responses was 8 h/work week. Reasons for contacting the CF centre varied greatly, but <20% of contacts were directly related to symptom management. In the second stage, 180 of 212 patients (85%) initiated 1876 contacts over 12 months. Factors associated with ≥5 contacts/year were female sex, FEV 1  ≤ 30% predicted, ≥5 physician visits/year, and ≥ 1 hospital admission/year. Answering unplanned patient-initiated contacts represented a significant workload for CF caregivers. Increased disease severity was associated with high contact frequency. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  13. Properties of CF/PA6 friction spun hybrid yarns for textile reinforced thermoplastic composites

    NASA Astrophysics Data System (ADS)

    Hasan, MMB; Nitsche, S.; Abdkader, A.; Cherif, Ch

    2017-10-01

    Due to their excellent strength, rigidity and damping properties as well as low weight, carbon fibre reinforced composites (CFRC) are widely being used for load bearing structures. On the other hand, with an increased demand und usage of CFRCs, effective methods to re-use waste carbon fibre (CF) materials, which are recoverable either from the process scraps or from the end-of-life components are attracting increased attention. In this paper, hybrid yarns consisting of staple CF and polyamide 6 (PA 6) are manufactured on a DREF-3000 friction spinning machine with various machine parameters such as spinning drum speed and suction air pressure. The relationship between different textile physical properties of the hybrid yarns, such as tensile strength and elongation with different spinning parameters and CF content of hybrid yarn is investigated. Furthermore, the tensile properties of uni-directional (UD) composites manufactured from the developed hybrid yarn shows 80% of the UD composite strength made from CF filament yarn.

  14. Conversion of adult endothelium to immunocompetent haematopoietic stem cells

    PubMed Central

    Lis, Raphael; Karrasch, Charles C.; Poulos, Michael G.; Kunar, Balvir; Redmond, David; Barcia Duran, Jose G.; Badwe, Chaitanya R.; Schachterle, Will; Ginsberg, Michael; Xiang, Jenny; Tabrizi, Arash Rafii; Shido, Koji; Rosenwaks, Zev; Elemento, Olivier; Speck, Nancy; Butler, Jason M.; Scandura, Joseph M.; Rafii, Shahin

    2018-01-01

    Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully converting adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of genes encoding the transcription factors Fosb, Gfi1, Runx1, and Spi1 (also known as Fgrs) and vascular-niche-derived angiocrine factors. The induction phase (day 0–8) of conversion is initiated by expression of Fgrs in mature endothelial cells, which results in endogenous Runx1 expression. During the specification phase (day 8–20), Runx1+ Fgrs-transduced endothelial cells commit to a haematopoietic fate yielding rEC-HSCs that no longer require Fgrs expression. The vascular niche drives a robust self-renewal and expansion phase of rEC-HSCs (at day 20–28). rEC-HSCs have a transcriptome and long-term self-renewal capacity similar to those of adult haematopoietic stem cells, are competent for clonal engraftment and serial primary and secondary multi-lineage reconstituting potential, including antigen-dependent adaptive immune function. Inhibition of TGF-β and CXCR7 or activation of BMP and CXCR4 signalling enhanced generation of rEC-HSCs. Conversion of endothelial cells into autologous authentic engraftable haematopoietic stem cells could aid treatment of haematological disorders. PMID:28514438

  15. Void statistics of the CfA redshift survey

    NASA Astrophysics Data System (ADS)

    Vogeley, Michael S.; Geller, Margaret J.; Huchra, John P.

    1991-11-01

    Clustering properties of two samples from the CfA redshift survey, each containing about 2500 galaxies, are studied. A comparison of the velocity distributions via a K-S test reveals structure on scales comparable with the extent of the survey. The void probability function (VPF) is employed for these samples to examine the structure and to test for scaling relations in the galaxy distribution. The galaxy correlation function is calculated via moments of galaxy counts. The shape and amplitude of the correlation function roughly agree with previous determinations. The VPFs for distance-limited samples of the CfA survey do not match the scaling relation predicted by the hierarchical clustering models. On scales not greater than 10/h Mpc, the VPFs for these samples roughly follow the hierarchical pattern. A variant of the VPF which uses nearly all the data in magnitude-limited samples is introduced; it accounts for the variation of the sampling density with velocity in a magnitude-limited survey.

  16. Void statistics of the CfA redshift survey

    NASA Technical Reports Server (NTRS)

    Vogeley, Michael S.; Geller, Margaret J.; Huchra, John P.

    1991-01-01

    Clustering properties of two samples from the CfA redshift survey, each containing about 2500 galaxies, are studied. A comparison of the velocity distributions via a K-S test reveals structure on scales comparable with the extent of the survey. The void probability function (VPF) is employed for these samples to examine the structure and to test for scaling relations in the galaxy distribution. The galaxy correlation function is calculated via moments of galaxy counts. The shape and amplitude of the correlation function roughly agree with previous determinations. The VPFs for distance-limited samples of the CfA survey do not match the scaling relation predicted by the hierarchical clustering models. On scales not greater than 10/h Mpc, the VPFs for these samples roughly follow the hierarchical pattern. A variant of the VPF which uses nearly all the data in magnitude-limited samples is introduced; it accounts for the variation of the sampling density with velocity in a magnitude-limited survey.

  17. Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis.

    PubMed

    Kawaguchi, Daichi; Furutachi, Shohei; Kawai, Hiroki; Hozumi, Katsuto; Gotoh, Yukiko

    2013-01-01

    Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch ligand Delta-like 1 (Dll1) is required to maintain quiescent NSCs in the adult mouse subventricular zone. Dll1 protein is induced in activated NSCs and segregates to one daughter cell during mitosis. Dll1-expressing cells reside in close proximity to quiescent NSCs, suggesting a feedback signal for NSC maintenance by their sister cells and progeny. Our data suggest a model in which NSCs produce their own niche cells for their maintenance through asymmetric Dll1 inheritance at mitosis.

  18. Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis

    PubMed Central

    Kawaguchi, Daichi; Furutachi, Shohei; Kawai, Hiroki; Hozumi, Katsuto; Gotoh, Yukiko

    2013-01-01

    Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch ligand Delta-like 1 (Dll1) is required to maintain quiescent NSCs in the adult mouse subventricular zone. Dll1 protein is induced in activated NSCs and segregates to one daughter cell during mitosis. Dll1-expressing cells reside in close proximity to quiescent NSCs, suggesting a feedback signal for NSC maintenance by their sister cells and progeny. Our data suggest a model in which NSCs produce their own niche cells for their maintenance through asymmetric Dll1 inheritance at mitosis. PMID:23695674

  19. 75 FR 21161 - Airworthiness Directives; General Electric Company (GE) CJ610 Series Turbojet Engines and CF700...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    ... Airworthiness Directives; General Electric Company (GE) CJ610 Series Turbojet Engines and CF700 Series Turbofan... adopting a new airworthiness directive (AD) for GE CJ610 series turbojet engines and CF700 turbofan engines... part 39 with a proposed AD. The proposed AD applies to GE CJ610 series turbojet engines and CF700...

  20. Topological analysis of the CfA redshift survey

    NASA Technical Reports Server (NTRS)

    Vogeley, Michael S.; Park, Changbom; Geller, Margaret J.; Huchra, John P.; Gott, J. Richard, III

    1994-01-01

    We study the topology of large-scale structure in the Center for Astrophysics Redshift Survey, which now includes approximately 12,000 galaxies with limiting magnitude m(sub B) is less than or equal to 15.5. The dense sampling and large volume of this survey allow us to compute the topology on smoothing scales from 6 to 20/h Mpc; we thus examine the topology of structure in both 'nonlinear' and 'linear' regimes. On smoothing scales less than or equal to 10/h Mpc this sample has 3 times the number of resolution elements of samples examined in previous studies. Isodensity surface of the smoothed galaxy density field demonstrate that coherent high-density structures and large voids dominate the galaxy distribution. We compute the genus-threshold density relation for isodensity surfaces of the CfA survey. To quantify phase correlation in these data, we compare the CfA genus with the genus of realizations of Gaussian random fields with the power spectrum measured for the CfA survey. On scales less than or equal to 10/h Mpc the observed genus amplitude is smaller than random phase (96% confidence level). This decrement reflects the degree of phase coherence in the observed galaxy distribution. In other words the genus amplitude on these scales is not good measure of the power spectrum slope. On scales greater than 10/h Mpc, where the galaxy distribution is rougly in the 'linear' regime, the genus ampitude is consistent with the random phase amplitude. The shape of the genus curve reflects the strong coherence in the observed structure; the observed genus curve appears broader than random phase (94% confidence level for smoothing scales less than or equal to 10/h Mpc) because the topolgoy is spongelike over a very large range of density threshold. This departre from random phase consistent with a distribution like a filamentary net of 'walls with holes.' On smoothing scales approaching approximately 20/h Mpc the shape of the CfA genus curve is consistent with random phase

  1. Circulating cell-free DNA: an up-coming molecular marker in exercise physiology.

    PubMed

    Breitbach, Sarah; Tug, Suzan; Simon, Perikles

    2012-07-01

    The phenomenon of circulating cell-free DNA (cfDNA) concentrations is of importance for many biomedical disciplines including the field of exercise physiology. Increases of cfDNA due to exercise are described to be a potential hallmark for the overtraining syndrome and might be related to, or trigger adaptations of, immune function induced by strenuous exercise. At the same time, exercise provides a practicable model for studying the phenomenon of cfDNA that is described to be of pathophysiological relevance for different topics in clinical medicine like autoimmune diseases and cancer. In this review, we are summarizing the current knowledge of exercise-based acute and chronic alterations in cfDNA levels and their physiological significance. The effects of acute exercise on cfDNA concentrations have been investigated in resistance exercises and in continuous, stepwise and interval endurance exercises of different durations. cfDNA concentrations peaked immediately after acute exercise and showed a rapid return to baseline levels. Typical markers of skeletal muscle damage (creatine kinase, uric acid, C-reactive protein) show delayed kinetics compared with the cfDNA peak response. Exercise parameters such as intensity, duration or average energy expenditure do not explain the extent of increasing cfDNA concentrations after strenuous exercise. This could be due to complex processes inside the human organism during and after physical activity. Therefore, we hypothesize composite effects of different physiological stress parameters that come along with exercise to be responsible for increasing cfDNA concentrations. We suggest that due to acute stress, cfDNA levels increase rapidly by a spontaneous active or passive release mechanism that is not yet known. As a result of the rapid and parallel increase of cfDNA and lactate in an incremental treadmill test leading to exhaustion within 15-20 minutes, it is unlikely that cfDNA is released into the plasma by typical necrosis

  2. Impact of enzymatic digestion on bacterial community composition in CF airway samples.

    PubMed

    Williamson, Kayla M; Wagner, Brandie D; Robertson, Charles E; Johnson, Emily J; Zemanick, Edith T; Harris, J Kirk

    2017-01-01

    Previous studies have demonstrated the importance of DNA extraction methods for molecular detection of Staphylococcus, an important bacterial group in cystic fibrosis (CF). We sought to evaluate the effect of enzymatic digestion (EnzD) prior to DNA extraction on bacterial communities identified in sputum and oropharyngeal swab (OP) samples from patients with CF. DNA from 81 samples (39 sputum and 42 OP) collected from 63 patients with CF was extracted in duplicate with and without EnzD. Bacterial communities were determined by rRNA gene sequencing, and measures of alpha and beta diversity were calculated. Principal Coordinate Analysis (PCoA) was used to assess differences at the community level and Wilcoxon Signed Rank tests were used to compare relative abundance (RA) of individual genera for paired samples with and without EnzD. Shannon Diversity Index (alpha-diversity) decreased in sputum and OP samples with the use of EnzD. Larger shifts in community composition were observed for OP samples (beta-diversity, measured by Morisita-Horn), whereas less change in communities was observed for sputum samples. The use of EnzD with OP swabs resulted in significant increase in RA for the genera Gemella ( p  < 0.01), Streptococcus ( p  < 0.01), and Rothia ( p  < 0.01). Staphylococcus ( p  < 0.01) was the only genus with a significant increase in RA from sputum, whereas the following genera decreased in RA with EnzD: Veillonella ( p  < 0.01), Granulicatella ( p  < 0.01), Prevotella ( p  < 0.01), and Gemella ( p  = 0.02). In OP samples, higher RA of Gram-positive taxa was associated with larger changes in microbial community composition. We show that the application of EnzD to CF airway samples, particularly OP swabs, results in differences in microbial communities detected by sequencing. Use of EnzD can result in large changes in bacterial community composition, and is particularly useful for detection of Staphylococcus in CF OP samples. The enhanced

  3. The A3 adenosine receptor agonist CF502 inhibits the PI3K, PKB/Akt and NF-kappaB signaling pathway in synoviocytes from rheumatoid arthritis patients and in adjuvant-induced arthritis rats.

    PubMed

    Ochaion, A; Bar-Yehuda, S; Cohen, S; Amital, H; Jacobson, K A; Joshi, B V; Gao, Z G; Barer, F; Patoka, R; Del Valle, L; Perez-Liz, G; Fishman, P

    2008-08-15

    The A(3) adenosine receptor (A(3)AR) is over-expressed in inflammatory cells and was defined as a target to combat inflammation. Synthetic agonists to this receptor, such as IB-MECA and Cl-IB-MECA, exert an anti-inflammatory effect in experimental animal models of adjuvant- and collagen-induced arthritis. In this study we present a novel A(3)AR agonist, CF502, with high affinity and selectivity at the human A(3)AR. CF502 induced a dose dependent inhibitory effect on the proliferation of fibroblast-like synoviocytes (FLS) via de-regulation of the nuclear factor-kappa B (NF-kappaB) signaling pathway. Furthermore, CF502 markedly suppressed the clinical and pathological manifestations of adjuvant-induced arthritis (AIA) in a rat experimental model when given orally at a low dose (100 microg/kg). As is typical of other G-protein coupled receptors, the A(3)AR expression level was down-regulated shortly after treatment with agonist CF502 in paw and in peripheral blood mononuclear cells (PBMCs) derived from treated AIA animals. Subsequently, a decrease in the expression levels of protein kinase B/Akt (PKB/Akt), IkappaB kinase (IKK), I kappa B (IkappaB), NF-kappaB and tumor necrosis factor-alpha (TNF-alpha) took place. In addition, the expression levels of glycogen synthase kinase-3 beta (GSK-3beta), beta-catenin, and poly(ADP-ribose)polymerase (PARP), known to control the level and activity of NF-kappaB, were down-regulated upon treatment with CF502. Taken together, CF502 inhibits FLS growth and the inflammatory manifestations of arthritis, supporting the development of A(3)AR agonists for the treatment of rheumatoid arthritis.

  4. Comparison of the Functional microRNA Expression in Immune Cell Subsets of Neonates and Adults

    PubMed Central

    Yu, Hong-Ren; Hsu, Te-Yao; Huang, Hsin-Chun; Kuo, Ho-Chang; Li, Sung-Chou; Yang, Kuender D.; Hsieh, Kai-Sheng

    2016-01-01

    Diversity of biological molecules in newborn and adult immune cells contributes to differences in cell function and atopic properties. Micro RNAs (miRNAs) are reported to involve in the regulation of immune system. Therefore, determining the miRNA expression profile of leukocyte subpopulations is important for understanding immune system regulation. In order to explore the unique miRNA profiling that contribute to altered immune in neonates, we comprehensively analyzed the functional miRNA signatures of eight leukocyte subsets (polymorphonuclear cells, monocytes, CD4+ T cells, CD8+ T cells, natural killer cells, B cells, plasmacytoid dendritic cells, and myeloid dendritic cells) from both neonatal and adult umbilical cord and peripheral blood samples, respectively. We observed distinct miRNA profiles between adult and neonatal blood leukocyte subsets, including unique miRNA signatures for each cell lineage. Leukocyte miRNA signatures were altered after stimulation. Adult peripheral leukocytes had higher let-7b-5p expression levels compared to neonatal cord leukocytes across multiple subsets, irrespective of stimulation. Transfecting neonatal monocytes with a let-7b-5p mimic resulted in a reduction of LPS-induced interleukin (IL)-6 and TNF-α production, while transfection of a let-7b-5p inhibitor into adult monocytes enhanced IL-6 and TNF-α production. With this functional approach, we provide intact differential miRNA expression profiling of specific immune cell subsets between neonates and adults. These studies serve as a basis to further understand the altered immune response observed in neonates and advance the development of therapeutic strategies. PMID:28066425

  5. Synergistic use of adult and embryonic stem cells to study human hematopoiesis.

    PubMed

    Martin, Colin H; Kaufman, Dan S

    2005-10-01

    Embryonic stem cells (ESCs) and adult stem cells both provide important resources to define the mechanisms of hematopoietic cell development. To date, studies that utilize hematopoietic stem cells (HSCs) isolated from sites such as bone marrow or umbilical cord blood have been the primary means to identify molecular and phenotypic characteristics of blood cell populations able to mediate long-term hematopoietic engraftment. Although these HSCs are very useful clinically, they are difficult to expand in culture. Now, basic research on human ESCs provides opportunities for novel investigations into the mechanisms of HSC self-renewal. Eventually, the long history of basic and clinical research with adult hematopoietic cell transplantation could translate to establish human ESCs as a suitable alternative starting cell source for clinical hematopoietic reconstitution.

  6. Sprouty1 Regulates Reversible Quiescence of a Self-Renewing Adult Muscle Stem Cell Pool during Regeneration

    PubMed Central

    Shea, Kelly L.; Xiang, Wanyi; LaPorta, Vincent S.; Licht, Jonathan D.; Keller, Charles; Basson, M. Albert; Brack, Andrew S.

    2010-01-01

    Summary Satellite cells are a heterogeneous population of skeletal muscle specific stem cells capable of self-renewal and differentiation after transplantation. Whether quiescent satellite cells can self-renew and contribute to muscle fiber repair in their endogenous environment in normal regenerating muscle has remained unknown. The transcription factor Pax7 is expressed in satellite cells and is critical for establishing the adult satellite cell pool. Using a temporally-inducible genetic lineage tracing approach (Pax7-CreERtm; R26R-lacZ) to fate-map adult satellite cells, we show that in response to injury quiescent adult Pax7+ cells enter the cell cycle; a subpopulation return to quiescence to fully replenish the satellite cell compartment and the others contribute to de novo muscle fiber formation. We demonstrate that Sprouty1 (Spry1), an inhibitor of receptor tyrosine kinase signaling, is robustly expressed in quiescent Pax7+ satellite cells in uninjured adult muscle, down-regulated in proliferating myogenic cells in injured muscles, and re-induced as Pax7+ cells return to quiescence in regenerated muscles. We show through deletion of Spry1 specifically in cycling adult Pax7+ satellite cells, that Spry1 is required for the return to quiescence and homeostasis of the self-renewing Pax7+ satellite cell pool during repair. Satellite cells unable to return to quiescence succumb to apoptosis leading to a diminished self-renewing Pax7-derived satellite cell pool. Our results define a novel role for Spry1 in adult stem cell biology and tissue repair. PMID:20144785

  7. Experimental ion mobility measurements for the LCTPC collaboration—Ar-CF4 mixtures

    NASA Astrophysics Data System (ADS)

    Santos, M. A. G.; Kaja, M. A.; Cortez, A. F. V.; Veenhof, R.; Neves, P. N. B.; Santos, F. P.; Borges, F. I. G. M.; Conde, C. A. N.

    2018-04-01

    In this paper we present the results of the ion mobility measurements made in pure carbon tetrafluoride (CF4) and gaseous mixtures of argon with carbon tetrafluoride (Ar-CF4) for pressures ranging from 6 to 10 Torr (8–10.6 mbar) and for low reduced electric fields in the 10 Td to 25 Td range (2.4-6.1 kVṡcm‑1ṡbar‑1), at room temperature. The time of arrival spectra revealed only one peak throughout the entire range studied which was attributed to CF3+. However, for Ar concentrations above 70%, a bump starts to appear at the left side of the main peak for reduced electric fields higher than 15 Td, which was attributed to impurities. The reduced mobilities obtained from the peak centroid of the time-of-arrival spectra are presented for Ar concentrations in the 5%–95% range.

  8. Heterogeneous integration of adult-generated granule cells into the epileptic brain

    PubMed Central

    Murphy, Brian L.; Pun, Raymund Y.K.; Yin, Hulian; Faulkner, Christian R.; Loepke, Andreas W.; Danzer, Steve C.

    2011-01-01

    The functional impact of adult-generated granule cells in the epileptic brain is unclear, with data supporting both protective and maladaptive roles. These conflicting findings could be explained if new granule cells integrate heterogeneously, with some cells taking neutral or adaptive roles, while others contribute to recurrent circuitry supporting seizures. Here, we tested this hypothesis by completing detailed morphological characterizations of age- and experience-defined cohorts of adult-generated granule cells from transgenic mice. The majority of newborn cells exposed to an epileptogenic insult exhibited reductions in dendritic spine number, suggesting reduced excitatory input to these cells. A significant subset, however, exhibited higher spine numbers. These latter cells tended to have enlarged cell bodies, long basal dendrites or both. Moreover, cells with basal dendrites received significantly more recurrent mossy fiber input through their apical dendrites, indicating that these cells are robustly integrated into the pathological circuitry of the epileptic brain. These data imply that newborn cells play complex – and potentially conflicting – roles in epilepsy. PMID:21209195

  9. CF3DODA-Me induces apoptosis, degrades Sp1, and blocks the transformation phase of the blebbishield emergency program.

    PubMed

    Taoka, Rikiya; Jinesh, Goodwin G; Xue, Wenrui; Safe, Stephen; Kamat, Ashish M

    2017-05-01

    Cancer stem cells are capable of undergoing cellular transformation after commencement of apoptosis through the blebbishield emergency program in a VEGF-VEGFR2-dependent manner. Development of therapeutics targeting the blebbishield emergency program would thus be important in cancer therapy. Specificity protein 1 (Sp1) orchestrates the transcription of both VEGF and VEGFR2; hence, Sp1 could act as a therapeutic target. Here, we demonstrate that CF 3 DODA-Me induced apoptosis, degraded Sp1, inhibited the expression of multiple drivers of the blebbishield emergency program such as VEGFR2, p70S6K, and N-Myc through activation of caspase-3, inhibited reactive oxygen species; and inhibited K-Ras activation to abolish transformation from blebbishields as well as transformation in soft agar. These findings confirm CF 3 DODA-Me as a potential therapeutic candidate that can induce apoptosis and block transformation from blebbishields.

  10. Halogenation effects on electron collisions with CF3Cl, CF2Cl2, and CFCl3

    NASA Astrophysics Data System (ADS)

    Freitas, T. C.; Lopes, A. R.; Azeredo, A. D.; Bettega, M. H. F.

    2016-04-01

    We report differential and integral elastic cross sections for low-energy electron collisions with CF3Cl, CF2Cl2, and CFCl3 molecules for energies ranging from 0.1 eV to 30 eV. The calculations were performed using the Schwinger multichannel method with pseudopotentials in the static-exchange and static-exchange plus polarization approximations. The influence of the permanent electric dipole moment on the cross sections was included using the Born closure scheme. A very good agreement between our calculations and the experimental results of Jones [J. Chem. Phys. 84, 813 (1986)], Mann and Linder [J. Phys. B 25, 1621 (1992); 25, 1633 (1992)] and Hoshino et al. [J. Chem. Phys. 138, 214305 (2013)] was found. We also compare our results with the calculations of Beyer et al. [Chem. Phys. 255, 1 (2000)] using the R-matrix method, where we find good agreement with respect to the location of the resonances, and with the calculations of Hoshino et al. using the independent atom method with screening corrected additivity rule, where we find qualitative agreement at energies above 20 eV. Additional electronic structure calculations were carried out in order to help in the interpretation of the scattering results. The stabilization the lowest σ∗ resonance due to the exchange of fluorine by chlorine atoms (halogenation effect) follows a simple linear relation with the energy of the lowest unoccupied molecular orbitals and can be considered as a signature of the halogenation effect.

  11. Toxicity and Growth Assessments of Three Thermophilic Benthic Dinoflagellates (Ostreopsis cf. ovata, Prorocentrum lima and Coolia monotis) Developing in the Southern Mediterranean Basin.

    PubMed

    Ben-Gharbia, Hela; Yahia, Ons Kéfi-Daly; Amzil, Zouher; Chomérat, Nicolas; Abadie, Eric; Masseret, Estelle; Sibat, Manoella; Zmerli Triki, Habiba; Nouri, Habiba; Laabir, Mohamed

    2016-10-15

    Harmful benthic dinoflagellates, usually developing in tropical areas, are expanding to temperate ecosystems facing water warming. Reports on harmful benthic species are particularly scarce in the Southern Mediterranean Sea. For the first time, three thermophilic benthic dinoflagellates ( Ostreopsis cf. ovata , Prorocentrum lima and Coolia monotis ) were isolated from Bizerte Bay (Tunisia, Mediterranean) and monoclonal cultures established. The ribotyping confirmed the morphological identification of the three species. Maximum growth rates were 0.59 ± 0.08 d -1 for O. cf. ovata , 0.35 ± 0.01 d -1 for C. monotis and 0.33 ± 0.04 d -1 for P. lima. Toxin analyses revealed the presence of ovatoxin-a and ovatoxin-b in O. cf. ovata cells. Okadaic acid and dinophysistoxin-1 were detected in P. lima cultures. For C. monotis , a chromatographic peak at 5.6 min with a mass m / z = 1061.768 was observed, but did not correspond to a mono-sulfated analogue of the yessotoxin. A comparison of the toxicity and growth characteristics of these dinoflagellates, distributed worldwide, is proposed.

  12. Toxicity and Growth Assessments of Three Thermophilic Benthic Dinoflagellates (Ostreopsis cf. ovata, Prorocentrum lima and Coolia monotis) Developing in the Southern Mediterranean Basin

    PubMed Central

    Ben-Gharbia, Hela; Yahia, Ons Kéfi-Daly; Amzil, Zouher; Chomérat, Nicolas; Abadie, Eric; Masseret, Estelle; Sibat, Manoella; Zmerli Triki, Habiba; Nouri, Habiba; Laabir, Mohamed

    2016-01-01

    Harmful benthic dinoflagellates, usually developing in tropical areas, are expanding to temperate ecosystems facing water warming. Reports on harmful benthic species are particularly scarce in the Southern Mediterranean Sea. For the first time, three thermophilic benthic dinoflagellates (Ostreopsis cf. ovata, Prorocentrum lima and Coolia monotis) were isolated from Bizerte Bay (Tunisia, Mediterranean) and monoclonal cultures established. The ribotyping confirmed the morphological identification of the three species. Maximum growth rates were 0.59 ± 0.08 d−1 for O. cf. ovata, 0.35 ± 0.01 d−1 for C. monotis and 0.33 ± 0.04 d−1 for P. lima. Toxin analyses revealed the presence of ovatoxin-a and ovatoxin-b in O. cf. ovata cells. Okadaic acid and dinophysistoxin-1 were detected in P. lima cultures. For C. monotis, a chromatographic peak at 5.6 min with a mass m/z = 1061.768 was observed, but did not correspond to a mono-sulfated analogue of the yessotoxin. A comparison of the toxicity and growth characteristics of these dinoflagellates, distributed worldwide, is proposed. PMID:27754462

  13. Laucysteinamide A, a Hybrid PKS/NRPS Metabolite from a Saipan Cyanobacterium, cf. Caldora penicillata

    PubMed Central

    Zhang, Chen; Naman, C. Benjamin; Engene, Niclas; Gerwick, William H.

    2017-01-01

    A bioactivity guided study of a cf. Caldora penicillata species, collected during a 2013 expedition to the Pacific island of Saipan, Northern Mariana Islands (a commonwealth of the USA), led to the isolation of a new thiazoline-containing alkaloid, laucysteinamide A (1). Laucysteinamide A is a new monomeric analogue of the marine cyanobacterial metabolite, somocystinamide A (2), a disulfide-bonded dimeric compound that was isolated previously from a Fijian marine cyanobacterium. The structure and absolute configuration of laucysteinamide A (1) was determined by a detailed analysis of its NMR, MS, and CD spectra. In addition, the highly bioactive lipid, curacin D (3), was also found to be present in this cyanobacterial extract. The latter compound was responsible for the potent cytotoxicity of this extract to H-460 human non-small cell lung cancer cells in vitro. PMID:28420100

  14. Laucysteinamide A, a Hybrid PKS/NRPS Metabolite from a Saipan Cyanobacterium, cf. Caldora penicillata.

    PubMed

    Zhang, Chen; Naman, C Benjamin; Engene, Niclas; Gerwick, William H

    2017-04-14

    A bioactivity guided study of a cf. Caldora penicillata species, collected during a 2013 expedition to the Pacific island of Saipan, Northern Mariana Islands (a commonwealth of the USA), led to the isolation of a new thiazoline-containing alkaloid, laucysteinamide A ( 1 ). Laucysteinamide A is a new monomeric analogue of the marine cyanobacterial metabolite, somocystinamide A ( 2 ), a disulfide-bonded dimeric compound that was isolated previously from a Fijian marine cyanobacterium. The structure and absolute configuration of laucysteinamide A ( 1 ) was determined by a detailed analysis of its NMR, MS, and CD spectra. In addition, the highly bioactive lipid, curacin D ( 3 ), was also found to be present in this cyanobacterial extract. The latter compound was responsible for the potent cytotoxicity of this extract to H-460 human non-small cell lung cancer cells in vitro.

  15. Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients.

    PubMed

    Novel-Catin, Etienne; Pelletier, Solenne; Reynaud, Quitterie; Nove-Josserand, Raphaele; Durupt, Stephane; Dubourg, Laurence; Durieu, Isabelle; Fouque, Denis

    2018-04-18

    Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.

  16. Cystic fibrosis - Comparison between patients in paediatric and adult age.

    PubMed

    Santos, V; Cardoso, A V; Lopes, C; Azevedo, P; Gamboa, F; Amorim, A

    Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. Although most cases are diagnosed in childhood, diagnosis in adults is apparently increasing. Evaluate the adult population with CF, comparing patients who were diagnosed before and after 18 years of age. Retrospective analysis of patients followed in three main medical centres in Portugal in 2012. Comparison of two groups: G1 - patients diagnosed at <18 years and G2 - patients diagnosed at ≥18 years. 89 adults were identified: 61.8% in G1, 38.2% in G2. Gender distribution was similar in both groups. Average age in G2 was higher (38.3±8.4 vs. 26.8±6.1 years, p<0.001). Respiratory symptoms most frequently led to CF diagnosis in all patients, mainly in adulthood. There was a greater percentage of patients homozygous for the mutation delF508 in G1 (43.6 vs. 8.8%, p=0.02). Respiratory and pancreatic function, and body mass index (BMI) showed a higher severity in G1 (G1 vs. G2: FEV1: 54.6±27.3 vs. 29.9±64.6%, p=0.177; pancreatic insufficiency 72.7 vs. 26.5%, p<0.001; BMI 20.2±3.4 vs. 22.2±4.8, p=0.018). Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus were the most frequently isolated microorganisms. Lung transplantation rate was higher in G2 (20.6 vs. 10.9%, p=0.231) while mortality rate was higher in G1 (0 vs. 3.6%, p=0.261). Hospital admission rate was higher in G1 as well as mortality rate. The results suggest that patients with CF diagnosed in childhood have characteristics that distinguish them from those diagnosed in adulthood, and these differences may have implications for diagnosis, prognosis and life expectancy. Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

  17. Prospects of Pluripotent and Adult Stem Cells for Rare Diseases.

    PubMed

    García-Castro, Javier; Singeç, Ilyas

    2017-01-01

    Rare diseases are highly diverse and complex regarding molecular underpinning and clinical manifestation and afflict millions of patients worldwide. The lack of appropriate model systems with face and construct validity and the limited availability of live tissues and cells from patients has largely hampered the understanding of underlying disease mechanisms. As a consequence, there are no adequate treatment options available for the vast majority of rare diseases. Over the last decade, remarkable progress in pluripotent and adult stem cell biology and the advent of powerful genomic technologies opened up exciting new avenues for the investigation, diagnosis, and personalized therapy of intractable human diseases. Utilizing the entire range of available stem cell types will continue to cross-fertilize different research areas and leverage the investigation of rare diseases based on evidence-based medicine. Standardized cell engineering and manufacturing from inexhaustible stem cell sources should lay the foundation for next-generation drug discovery and cell therapies that are broadly applicable in regenerative medicine. In this chapter we discuss how patient- and disease-specific iPS cells as well as adult stem cells are changing the pace of biomedical research and the translational landscape.

  18. Sickle cell crisis in the adult: chest radiographic findings and comparison with pediatric sickle cell disease.

    PubMed

    Miller, J A; Hinrichs, C R

    2001-02-01

    With the advent of improved therapy, an increasing proportion of individuals suffering from sickle cell disease (SCD) are surviving into adulthood. In contrast to children, little has been documented concerning the typical radiographic findings in adults presenting with sickle cell crises (SCC). We describe the chest radiographic (CXR) manifestations of adults with SCD presenting in SSC, correlated to hemoglobin (Hb) values, and compare them to those of the pediatric sickle cell population. The chest radiographs of 66 consecutive adults presenting to our emergency department complaining of symptoms consistent with acute SCC were retrospectively reviewed over a 12-month period. The radiographic findings were correlated with admission Hb values and compared with those of 50 children with known SCD presenting with SCC. Chi square analysis revealed no significant difference between the cardiovascular and bony findings in the adults and in those of the pediatric controls (p > 0.08-p > 1.0). However, one important difference in the two cohorts was that upper lobe infiltrates occurred exclusively in the pediatric group (p = 0.06). There was a statistically significant (p < 0.05) difference in cardiovascular and skeletal abnormalities between adults with Hb above and below the mean (8.2 g/dL). The radiographic features of adults presenting in acute SCCs are similar to those of children. Although the chest radiograph is often normal, in decreasing frequency, cardiovascular abnormalities, pneumonia sparing the upper lobes, and aseptic osteonecrosis of the shoulders and spine are not uncommon. There is a significant relationship, however, between cardiovascular abnormalities and Hb levels.

  19. Perceptions of young adults with sickle cell disease concerning their disease experience.

    PubMed

    Matthie, Nadine; Hamilton, Jill; Wells, Diana; Jenerette, Coretta

    2016-06-01

    To describe the perceptions of young adults with sickle cell disease concerning their disease experience. Sickle cell disease is a lifelong, genetic condition with both acute and chronic painful exacerbations. Little is known of the experiences of young adults with sickle cell disease. This study used a qualitative, descriptive design with semi-structured, life review interviews. Between August 2010-September 2012, purposive sampling was used to recruit participants with a known sickle cell disease diagnosis who were ages 18-35 years, were being seen in an outpatient sickle cell clinic and were English speaking. Participants provided demographic information and responded to two interviews. A content analysis was then used to interpret participants' narratives of their experiences of living with sickle cell disease. A sample of 29 young adults with sickle cell disease consisted of 79·3% females, 35·6% employed full-time or part-time, 71·6% single/never married and 57·8% with sickle cell anaemia. Their mean age was 25·8 with 13·2 years of education. Four major interview themes were identified: (1) struggles to maintain or achieve good quality of life or life satisfactions; (2) strategies to maintain self-care; (3) interruptions to family, work and social roles; and (4) difficulties accessing needed health care. Young adults face many challenges while living with sickle cell disease. With a better understanding of their disease experience and how it influences their quality of life, researchers can begin tailoring appropriate interventions to improve health outcomes in this vulnerable, minority population. © 2015 John Wiley & Sons Ltd.

  20. Epithelial cell specific properties and genetic complementation in a delta F508 cystic fibrosis nasal polyp cell line.

    PubMed

    Kunzelmann, K; Lei, D C; Eng, K; Escobar, L C; Koslowsky, T; Gruenert, D C

    1995-09-01

    Analysis of vectorial ion transport and protein trafficking in transformed cystic fibrosis (CF) epithelial cells has been limited because the cells tend to lose their tight junctions with multiple subcultures. To elucidate ion transport and protein trafficking in CF epithelial cells, a polar cell line with apical and basolateral compartments will facilitate analysis of the efficacy of different gene therapy strategies in a "tight epithelium" in vitro. This study investigates the genotypic and phenotypic properties of a CF nasal polyp epithelial, delta F508 homozygote, cell line that has tight junctions pre-crisis. The cells (sigma CFNPE14o-) were transformed with an origin-of-replication defective SV40 plasmid. They develop transepithelial resistance in Ussing chambers and are defective in cAMP-dependent Cl- transport as measured by efflux of radioactive Cl-, short circuit current (Isc), or whole-cell patch clamp. Stimulation of the cells by bradykinin, histamine, or ATP seems to activate both K(+)- and Ca(+2)-dependent Cl- transport. Measurement of 36Cl- efflux following stimulation with A23187 and ionomycin indicate a Ca(+2)-dependent Cl- transport. Volume regulatory capacity of the cells is indicated by cell swelling conductance. Expression of the CF transmembrane conductance regulator mRNA was indicated by RT-PCR amplification. When cells are grown at 26 degrees C for 48 h there is no indication of cAMP-dependent Cl- as has been previously indicated in heterologous expression systems. Antibodies specific for secretory cell antigens indicate the presence of antigens found in goblet, serous, and mucous cells; in goblet and serous cells; or in goblet and mucous cells; but not antigens found exclusively in mucous or serous cells.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Sequoia regulates cell fate decisions in the external sensory organs of adult Drosophila.

    PubMed

    Andrews, Hillary K; Giagtzoglou, Nikolaos; Yamamoto, Shinya; Schulze, Karen L; Bellen, Hugo J

    2009-06-01

    The adult Drosophila external sensory organ (ESO), comprising the hair, socket, neuron, sheath and glia cells, arises through the asymmetric division of sensory organ precursor cells (SOPs). In a mosaic screen designed to identify new components in ESO development, we isolated mutations in sequoia, which encodes a putative zinc-finger transcription factor that has previously been shown to have a role in dendritogenesis. Here, we show that adult clones mutant for seq exhibit a loss of hair cells and a gain of socket cells. We propose that the seq mutant phenotype arises, in part, owing to the loss of several crucial transcription factors known to be important in peripheral nervous system development such as D-Pax2, Prospero and Hamlet. Thus, Sequoia is a new upstream regulator of genes that orchestrates cell fate specification during development of the adult ESO lineage.

  2. Sequoia regulates cell fate decisions in the external sensory organs of adult Drosophila

    PubMed Central

    Andrews, Hillary K; Giagtzoglou, Nikolaos; Yamamoto, Shinya; Schulze, Karen L; Bellen, Hugo J

    2009-01-01

    The adult Drosophila external sensory organ (ESO), comprising the hair, socket, neuron, sheath and glia cells, arises through the asymmetric division of sensory organ precursor cells (SOPs). In a mosaic screen designed to identify new components in ESO development, we isolated mutations in sequoia, which encodes a putative zinc-finger transcription factor that has previously been shown to have a role in dendritogenesis. Here, we show that adult clones mutant for seq exhibit a loss of hair cells and a gain of socket cells. We propose that the seq mutant phenotype arises, in part, owing to the loss of several crucial transcription factors known to be important in peripheral nervous system development such as D-Pax2, Prospero and Hamlet. Thus, Sequoia is a new upstream regulator of genes that orchestrates cell fate specification during development of the adult ESO lineage. PMID:19444309

  3. Spin transition of ferric iron in the calcium-ferrite type aluminous phase: Fe 3+ Spin Transition in the CF Phase

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

    Wu, Ye; Qin, Fei; Wu, Xiang

    2017-08-01

    We investigated Fe-free and Fe-bearing CF phases using nuclear forward scattering and X-ray diffraction coupled with diamond anvil cells up to 80 GPa at room temperature. Octahedral Fe3+ ions in the Fe-bearing CF phase undergo a high-spin to low-spin transition at 25–35 GPa, accompanied by a volume reduction of ~2.0% and a softening of bulk sound velocity up to 17.6%. Based on the results of this study and our previous studies, both the NAL and CF phases, which account for 10–30 vol % of subducted MORB in the lower mantle, are predicted to undergo a spin transition of octahedral Fe3+more » at lower mantle pressures. Spin transitions in these two aluminous phases result in an increase of density of 0.24% and a pronounced softening of bulk sound velocity up to 2.3% for subducted MORB at 25–60 GPa and 300 K. The anomalous elasticity region expands and moves to 30–75 GPa at 1200 K and the maximum of the VΦ reduction decreases to ~1.8%. This anomalous elastic behavior of Fe-bearing aluminous phases across spin transition zones may be relevant in understanding the observed seismic signatures in the lower mantle.« less

  4. Lost in translation? How adults living with Cystic Fibrosis understand treatment recommendations from their healthcare providers, and the impact on adherence to therapy.

    PubMed

    Pakhale, S; Baron, J; Armstrong, M; Tasca, G; Gaudet, E; Aaron, S D; Cameron, W; Balfour, L

    2016-08-01

    This study builds on the limited research documenting Cystic Fibrosis (CF) patients' understanding of treatment recommendations and how this may impact adherence to therapy. We surveyed adults with CF and their healthcare professional (HCP) to capture treatment recommendations provided by the HCP, and patients' knowledge, and frequency of performance, of these recommendations. We classified CF participants' understanding of treatment recommendations (correct/incorrect) as compared to the actual recommendations made by the HCP. We computed CF participants' adherence in relation to HCP treatment recommendations and to their own understanding of treatment recommendations (adherent/non-adherent). Complete HCP and patient data were available for 42 participants. The recommended treatment frequency was correctly understood by 0%-87.8% of CF participants. Adherence to HCP treatment recommendations ranged from 0 to 68.3% (mean 45.4%±21.5), and rates were low (<33%) for acapella, percussion/postural drainage, tobramycin nebulization and insulin. Participants' adherence was greater when calculated in relation to participants' understanding of treatment recommendations (62.4%±25.1) than when calculated in relation to actual HCP treatment recommendations (45.4%±21.5%) (p=0.009). Adults with CF misunderstand treatment recommendations; this likely affects treatment adherence. Interventions to ensure HCPs use effective communication strategies are needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Treatment of dry eye syndrome with orally administered CF101: data from a phase 2 clinical trial.

    PubMed

    Avni, Isaac; Garzozi, Hanna J; Barequet, Irina S; Segev, Fanni; Varssano, David; Sartani, Gil; Chetrit, Noa; Bakshi, Erez; Zadok, David; Tomkins, Oren; Litvin, Gilad; Jacobson, Kenneth A; Fishman, Sari; Harpaz, Zivit; Farbstein, Motti; Yehuda, Sara Bar; Silverman, Michael H; Kerns, William D; Bristol, David R; Cohn, Ilan; Fishman, Pnina

    2010-07-01

    To explore the safety and efficacy of CF101, an A(3) adenosine receptor agonist, in patients with moderate to severe dry eye syndrome. Phase 2, multicenter, randomized, double-masked, placebo-controlled, parallel-group study. Sixty-eight patients completed the study, 35 patients in the placebo group and 33 patients in the CF101 group. Patients were treated orally with either 1 mg CF101 pills or matching vehicle-filled placebo pills, given twice daily for 12 weeks, followed by a 2-week posttreatment observation. An improvement of more than 25% over baseline at week 12 in one of the following parameters: (1) tear break-up time (BUT); (2) superficial punctate keratitis assessed by fluorescein staining results; and (3) Schirmer tear test 1 results. Clinical laboratory safety tests, ophthalmic examinations, intraocular pressure (IOP) measurements, electrocardiographic evaluations, vital sign measurements, and monitoring of adverse events. A statistically significant increase in the proportion of patients who achieved more than 25% improvement in the corneal staining and in the clearance of corneal staining was noted between the CF101-treated group and the placebo group. Treatment with CF101 resulted in a statistically significant improvement in the mean change from baseline at week 12 of the corneal staining, BUT, and tear meniscus (TM) height in the CF101-treated group. CF101 was well tolerated and exhibited an excellent safety profile with no serious adverse events. A statistically significant decrease from baseline was observed in the IOP of the CF101-treated group in comparison with the placebo group. CF101, given orally, induced a statistically significant improvement in the corneal staining and an improvement in the BUT and TM in patients with moderate to severe dry eye syndrome. The drug was very well tolerated. These data and the anti-inflammatory characteristic of CF101 support further study of the drug as a potential treatment for the signs and symptoms of dry

  6. Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas

    PubMed Central

    Rovira, Meritxell; Scott, Sherri-Gae; Liss, Andrew S.; Jensen, Jan; Thayer, Sarah P.; Leach, Steven D.

    2009-01-01

    The question of whether dedicated progenitor cells exist in adult vertebrate pancreas remains controversial. Centroacinar cells and terminal duct (CA/TD) cells lie at the junction between peripheral acinar cells and the adjacent ductal epithelium, and are frequently included among cell types proposed as candidate pancreatic progenitors. However these cells have not previously been isolated in a manner that allows formal assessment of their progenitor capacities. We have found that a subset of adult CA/TD cells are characterized by high levels of ALDH1 enzymatic activity, related to high-level expression of both Aldh1a1 and Aldh1a7. This allows their isolation by FACS using a fluorogenic ALDH1 substrate. FACS-isolated CA/TD cells are relatively depleted of transcripts associated with differentiated pancreatic cell types. In contrast, they are markedly enriched for transcripts encoding Sca1, Sdf1, c-Met, Nestin, and Sox9, markers previously associated with progenitor populations in embryonic pancreas and other tissues. FACS-sorted CA/TD cells are uniquely able to form self-renewing “pancreatospheres” in suspension culture, even when plated at clonal density. These spheres display a capacity for spontaneous endocrine and exocrine differentiation, as well as glucose-responsive insulin secretion. In addition, when injected into cultured embryonic dorsal pancreatic buds, these adult cells display a unique capacity to contribute to both the embryonic endocrine and exocrine lineages. Finally, these cells demonstrate dramatic expansion in the setting of chronic epithelial injury. These findings suggest that CA/TD cells are indeed capable of progenitor function and may contribute to the maintenance of tissue homeostasis in adult mouse pancreas. PMID:20018761

  7. Electocardiographic findings in adult Nigerians with sickle cell anaemia.

    PubMed

    Oguanobi, N I; Onwubere, B J C; Ike, S O; Anisiuba, B C; Ejim, E C; Ibegbulam, O G

    2010-09-01

    Cardiovascular system abnormalities are common causes of morbidity and mortality in sickle cell anaemia. The study aims at determining the pattern of electrocardiographic changes in adult Nigerian sickle cell anaemia patients. A descriptive cross sectional study was done on sixty sickle cell anaemia patients seen at the adult sickle cell clinic of University of Nigeria Teaching Hospital (UNTH) Enugu, and sixty age and sex matched normal controls. All the subjects had clinical evaluation as well as electrocardiographic examination. The mean heart rate, P-wave duration, P-wave dispersion, PR interval, QRS duration, QRS dispersion, QTc interval and QTc dispersion were significantly higher in the patients than in the control group. Electrocardiographic abnormalities identified by this study were: left ventricular hypertrophy (75%; 1.7%), left atrial enlargement (40%; 0%), biventricular hypertrophy (11%; 0), ST-segment elevation (10%; 0%) and increased P-wave and QTc dispersions. ST segment elevation was found more in patients with moderate and severe anaemia (P= 0.02, Spearman correlation r= 0.342; P= 0.007), Sickle cell anaemia is associated with significant electrocardiographic abnormalities. Further prospective studies are recommended to evaluate the prognostic significance of the electrocardiographic intervals dispersion on the long term disease outcome in sickle cell anaemia.

  8. Seasonal variation in telencephalon cell proliferation in adult female tsinling dwarf skinks (Scincella tsinlingensis).

    PubMed

    Yang, Chun; Wang, Limin; Xing, Xiangyang; Gao, Yanyan; Guo, Li

    2017-05-01

    In adult mammals, neurogenesis is limited to specific niches in the brain, but considerable adult neurogenesis occurs in many brain regions in non-mammalian vertebrates. Non-mammalian vertebrates provide invaluable comparative material for understanding the core mechanisms of adult neural stem cell maintenance and fate, but phylogenetic differences in adult neurogenesis remain poorly understood. Here we examine cell proliferation seasonality in the telencephalon of adult female tsinling dwarf skinks (Scincella tsinlingensis) by injecting wild animals caught in summer, autumn and spring, and animals caught in autumn and raised under winter conditions, with 5-Bromo-2'-deoxyuridine (BrdU). Then, 24h, 7d and 28d after BrdU administration we examined brain tissue and quantified BrdU-labeled cells as a marker of neuronal proliferation. The highest number of labeled cells in the telencephalon was found in the 7d group. BrdU-positive cells were widely distributed in the anterior olfactory nucleus (AON), medial cortex (MC), dorsal cortex (DC), lateral cortex (LC), dorsal ventricular ridge (DVR), septum (SP), striatum (STR) and nucleus sphericus (NS). No BrdU-positive cells were detected in olfactory bulbs or elsewhere in the telencephalon. The highest proliferative levels were found in the AON in autumn. The NS exhibited relatively high levels of cell proliferation. The proliferative rate in the AON fluctuated seasonally as autumn>summer>spring>winter. Glial fibrillary acidic protein-positive cells were widely distributed in the telencephalon and their fibrous processes extended into brain parenchyma and anchored in the meninges. Doublecortin-positive newborn neurons of the subventricular zone appeared to migrate into the cerebral cortex via the radial migratory stream. Cell proliferation in the telencephalon of adult female S. tsinlingensis fluctuates seasonally, especially in regions related to olfactory memory. This is the first demonstration of proliferative activity in

  9. A theoretical study of the photoinduced desorption of I — from a CF3I dimer

    NASA Astrophysics Data System (ADS)

    Tossell, J. A.

    1997-04-01

    Ab initio SCF-MO calculations using effective core-potential basis sets are employed to evaluate ionization potentials and electron affinities for CF3I and the geometries and energies of the singlet and triplet states of the CF3I dimer. The calculated geometry of the single state of the dimer is in qualitative agreement with the experimental geometry for condensed phase CF3I. The calculated energy for vertical excitation from the singlet to the triplet state is 4.1 eV at the Hartree-Fock level and 4.5 eV after incorporation of correlation at the Moller-Plesset 2nd-order level, consistent with excitation by 193 nm (6.4 eV) light. The equilibrium geometry of the triplet consists essentially of a CF3I+, CF3I- ion pair, in which the Csbnd I bond distance in the anionic component has increased to 5.5Å, compared with 2.1Åin the neutral molecule. The calculated binding energy of the triplet ion pair is about 4 eV.

  10. Complete disassociation of adult pancreas into viable single cells through cold trypsin-EDTA digestion*

    PubMed Central

    Li, Dan; Peng, Shi-yun; Zhang, Zhen-wu; Feng, Rui-cheng; Li, Lu; Liang, Jie; Tai, Sheng; Teng, Chun-bo

    2013-01-01

    The in vitro isolation and analysis of pancreatic stem/progenitor cells are necessary for understanding their properties and function; however, the preparation of high-quality single-cell suspensions from adult pancreas is prerequisite. In this study, we applied a cold trypsin-ethylenediaminetetraacetic acid (EDTA) digestion method to disassociate adult mouse pancreata into single cells. The yield of single cells and the viability of the harvested cells were much higher than those obtained via the two commonly used warm digestion methods. Flow cytometric analysis showed that the ratio of ductal or BCRP1-positive cells in cell suspensions prepared through cold digestion was consistent with that found in vivo. Cell culture tests showed that pancreatic epithelial cells prepared by cold digestion maintained proliferative capacity comparable to those derived from warm collagenase digestion. These results indicate that cold trypsin-EDTA digestion can effectively disassociate an adult mouse pancreas into viable single cells with minimal cell loss, and can be used for the isolation and analysis of pancreatic stem/progenitor cells. PMID:23825145

  11. A putative mesenchymal stem cells population isolated from adult human testes.

    PubMed

    Gonzalez, R; Griparic, L; Vargas, V; Burgee, K; Santacruz, P; Anderson, R; Schiewe, M; Silva, F; Patel, A

    2009-08-07

    Mesenchymal stem cells (MSCs) isolated from several adult human tissues are reported to be a promising tool for regenerative medicine. In order to broaden the array of tools for therapeutic application, we isolated a new population of cells from adult human testis termed gonadal stem cells (GSCs). GSCs express CD105, CD166, CD73, CD90, STRO-1 and lack hematopoietic markers CD34, CD45, and HLA-DR which are characteristic identifiers of MSCs. In addition, GSCs express pluripotent markers Oct4, Nanog, and SSEA-4. GSCs propagated for at least 64 population doublings and exhibited clonogenic capability. GSCs have a broad plasticity and the potential to differentiate into adipogenic, osteogenic, and chondrogenic cells. These studies demonstrate that GSCs are easily obtainable stem cells, have growth kinetics and marker expression similar to MSCs, and differentiate into mesodermal lineage cells. Therefore, GSCs may be a valuable tool for therapeutic applications.

  12. Assessment of DNA synthesis in Islet-1{sup +} cells in the adult murine heart

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

    Weinberger, Florian, E-mail: f.weinberger@uke.de; Mehrkens, Dennis, E-mail: dennis.mehrkens@uk-koeln.de; Starbatty, Jutta, E-mail: starbatty@uke.uni-hamburg.de

    Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1{sup +}) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1{sup +} cells retain proliferative activitymore » and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ({sup 3}H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of {sup 3}H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1{sup +} cells. Whereas Islet{sup −} non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1{sup +} cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.« less

  13. Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: a pilot randomized study of high-dose vitamin D3 administration

    PubMed Central

    Alvarez, Jessica A.; Chong, Elizabeth Y.; Walker, Douglas I.; Chandler, Joshua D.; Michalski, Ellen S.; Grossmann, Ruth E.; Uppal, Karan; Li, Shuzhao; Frediani, Jennifer K.; Tirouvanziam, Rabindra; Tran, ViLinh T.; Tangpricha, Vin; Jones, Dean P.; Ziegler, Thomas R.

    2017-01-01

    Background Cystic fibrosis (CF) is a chronic catabolic disease often requiring hospitalization for acute episodes of worsening pulmonary exacerbations. Limited data suggest that vitamin D may have beneficial clinical effects, but the impact of vitamin D on systemic metabolism in this setting is unknown. Objective We used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin D status and high-dose vitamin D3 administration on systemic metabolism in adults with CF with an acute pulmonary exacerbation. Design Twenty-five hospitalized adults with CF were enrolled in a randomized trial of high-dose vitamin D3 (250,000 IU vitamin D3 bolus) versus placebo. Age-matched healthy subjects served as a reference group for baseline comparisons. Plasma was analyzed with liquid chromatography/ultra-high resolution mass spectrometry. Using recent HRM bioinformatics and metabolic pathway enrichment methods, we examined associations with baseline vitamin D status (sufficient vs deficient per serum 25-hydroxyvitamin D concentrations) and the 7-day response to vitamin D3 supplementation. Results Several amino acids and lipid metabolites differed between CF and healthy control subjects, indicative of an overall catabolic state. In CF subjects, 343 metabolites differed (P<0.05) by baseline vitamin D status and were enriched within 7 metabolic pathways including fatty acid, amino acid, and carbohydrate metabolism. A total of 316 metabolites, which showed enrichment for 15 metabolic pathways--predominantly representing amino acid pathways-- differed between the vitamin D3- and placebo-treated CF subjects over time (P<0.05). In the placebo group, several tricarboxylic acid cycle intermediates increased while several amino acid-related metabolites decreased; in contrast, little change in these metabolites occurred with vitamin D3 treatment. Conclusions Numerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D3

  14. Ultraviolet and infrared laser-induced fragmentation of free (CF{sub 3}I){sub n} clusters in a molecular beam and (CF{sub 3}I){sub n} clusters inside or on the surface of large (Xe){sub m} clusters

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

    Apatin, V. M.; Lokhman, V. N.; Makarov, G. N., E-mail: gmakarov@isan.troitsk.ru

    The fragmentation of free homogeneous (CF{sub 3}I){sub n} clusters in a molecular beam (n ≤ 45 is the average number of molecules in the cluster) and (CF{sub 3}I){sub n} clusters inside or on the surface of large (Xe){sub m} clusters (m ≥ 100 is the average number of atoms in the cluster) by ultraviolet and infrared laser radiations has been studied. These three types of (CF{sub 3}I){sub n} clusters are shown to have different stabilities with respect to fragmentation by both ultraviolet and infrared radiations and completely different dependences of the fragmentation probability on the energy of ultraviolet and infraredmore » radiations. When exposed to ultraviolet radiation, the free (CF{sub 3}I){sub n} clusters fragment at comparatively low fluences (Φ{sub UV} ≤ 0.15 J cm{sup −2}) and the weakest energy dependence of the fragmentation probability is observed for them. A stronger energy dependence of the fragmentation probability is observed for the (CF{sub 3}I){sub n} clusters localized inside (Xe){sub m} clusters, and the strongest dependence is observed for the (CF{sub 3}I){sub n} clusters located on the surface of (Xe){sub m} clusters. When the clusters are exposed to infrared radiation, the homogeneous (CF{sub 3}I){sub n} clusters efficiently fragment at low fluences (Φ{sub IR} ≤ 25 mJ cm{sup −2}), higher fluences (Φ{sub IR} ≈ 75 mJ cm{sup −2}) are needed for the fragmentation of the (CF{sub 3}I){sub n} localized inside (Xe){sub m} clusters, and even higher fluences (Φ{sub IR} ≈ 150 mJ cm{sup −2}) are needed for the fragmentation of the (CF{sub 3}I){sub n} clusters located on the surface of (Xe){sub m} clusters. It has been established that small (CF{sub 3}I){sub n} clusters located on the surface of (Xe){sub m} clusters do not fragment up to fluences Φ{sub IR} ≈ 250 mJ cm{sup −2}. The fragmentation efficiency of (CF{sub 3}I){sub n} clusters is shown to be the same (at the same fluence) when they are excited by both pulsed (

  15. Similar Responses of Intestinal T Cells From Untreated Children and Adults With Celiac Disease to Deamidated Gluten Epitopes.

    PubMed

    Ráki, Melinda; Dahal-Koirala, Shiva; Yu, Hao; Korponay-Szabó, Ilma R; Gyimesi, Judit; Castillejo, Gemma; Jahnsen, Jørgen; Qiao, Shuo-Wang; Sollid, Ludvig M

    2017-09-01

    Celiac disease is a chronic small intestinal inflammatory disorder mediated by an immune response to gluten peptides in genetically susceptible individuals. Celiac disease is often diagnosed in early childhood, but some patients receive a diagnosis late in life. It is uncertain whether pediatric celiac disease is distinct from adult celiac disease. It has been proposed that gluten-reactive T cells in children recognize deamidated and native gluten epitopes, whereas T cells from adults only recognize deamidated gluten peptides. We studied the repertoire of gluten epitopes recognized by T cells from children and adults. We examined T-cell responses against gluten by generating T-cell lines and T-cell clones from intestinal biopsies of adults and children and tested proliferative response to various gluten peptides. We analyzed T cells from 14 children (2-5 years old) at high risk for celiac disease who were followed for celiac disease development. We also analyzed T cells from 6 adults (26-55 years old) with untreated celiac disease. All children and adults were positive for HLA-DQ2.5. Biopsies were incubated with gluten digested with chymotrypsin (modified or unmodified by the enzyme transglutaminase 2) or the peptic-tryptic digest of gliadin (in native and deamidated forms) before T-cell collection. Levels of T-cell responses were higher to deamidated gluten than to native gluten in children and adults. T cells from children and adults each reacted to multiple gluten epitopes. Several T-cell clones were cross-reactive, especially clones that recognized epitopes from γ-and ω-gliadin. About half of the generated T-cell clones from children and adults reacted to unknown epitopes. T-cell responses to different gluten peptides appear to be similar between adults and children at the time of diagnosis of celiac disease. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. [Detection of KRAS mutation in colorectal cancer patients' cfDNA with droplet digital PCR].

    PubMed

    Luo, Yuwen; Li, Yao

    2018-03-25

    This study aims to develop a new method for the detection of KRAS mutations related to colorectal cancer in cfDNA, and to evaluate the sensitivity and accuracy of the detection. We designed a method of cfDNA based KRAS detection by droplets digital PCR (ddPCR). The theoretical performance of the method is evaluated by reference standard and compared to the ARMS PCR method. Two methods, ddPCR and qPCR, were successfully established to detect KRAS wild type and 7 mutants. Both methods were validated using plasmid standards and actual samples. The results were evaluated by false positive rate, linearity, and limit of detection. Finally, 52 plasma cfDNA samples from patients and 20 samples from healthy people were tested, the clinical sensitivity is 97.64%, clinical specificity is 81.43%. ddPCR method shows higher performance than qPCR. The LOD of ddPCR method reached single digits of cfDNA copies, it can detect as low as 0.01% to 0.04% mutation abundance.

  17. The Degradation Behavior of SiCf/SiO2 Composites in High-Temperature Environment

    NASA Astrophysics Data System (ADS)

    Yang, Xiang; Cao, Feng; Qing, Wang; Peng, Zhi-hang; Wang, Yi

    2018-04-01

    SiCf/SiO2 composites had been fabricated efficiently by Sol-Gel method. The oxidation behavior, thermal shock property and ablation behavior of SiCf/SiO2 composites was investigated. SiCf/SiO2 composites showed higher oxidation resistance in oxidation atmosphere, the flexural strength retention ratio was larger than 90.00%. After 1300 °C thermal shock, the mass retention ratio was 97.00%, and the flexural strength retention ratio was 92.60%, while after 1500 °C thermal shock, the mass retention ratio was 95.37%, and the flexural strength retention ratio was 83.34%. After 15 s ablation, the mass loss rate was 0.049 g/s and recession loss rate was 0.067 mm/s. The SiO2 matrix was melted in priority and becomes loosen and porous. With the ablation going on, the oxides were washed away by the shearing action of the oxyacetylene flame. The evaporation of SiO2 took away large amount of heat, which is also beneficial to the protection for SiCf/SiO2 composites.

  18. Electron Attachment to Halomethanes at High Temperature: CH2CI2, CF2CI2, CH3CI, and CF3CI Attachment Rate Constants up to 1100 K

    DTIC Science & Technology

    2009-08-01

    hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and...attachment reactions: 390i 50 meV (CH:Cl;). 124* 20 meV (CF2CI2), 670 + 70 meV (CH3CI), and 406±50 meV (CF,C1). Comparisons are made with existing data ...Research Laboratory, 29 Randolph Road, Hanscom Air Force Base . Massachusetts 01731-3010, USA (Received 15 May 2009; accepted 4 August 2009; published

  19. Sound velocities of Na0.4Mg0.6Al1.6Si0.4O4 NAL and CF phases to 73 GPa determined by Brillouin scattering method

    NASA Astrophysics Data System (ADS)

    Dai, Lidong; Kudo, Yuki; Hirose, Kei; Murakami, Motohiko; Asahara, Yuki; Ozawa, Haruka; Ohishi, Yasuo; Hirao, Naohisa

    2013-03-01

    The sound velocities of two aluminum-rich phases in the lower mantle, hexagonal new Al-rich phase (NAL) and its corresponding high-pressure polymorph orthorhombic Ca-ferrite-type phase (CF), were determined with the Brillouin scattering method in a pressure range from 9 to 73 GPa at room temperature. Both NAL and CF samples have identical chemical composition of Na0.4Mg0.6Al1.6Si0.4O4 (40 % NaAlSiO4-60 % MgAl2O4). Infrared laser annealing in the diamond anvil cell was performed to minimize the stress state of the sample and obtain the high-quality Brillouin spectra. The results show shear modulus at zero pressure G 0 = 121.960 ± 0.087 GPa and its pressure derivative G' = 1.961 ± 0.009 for the NAL phase, and G 0 = 129.653 ± 0.059 GPa and G' = 2.340 ± 0.004 for the CF phase. The zero-pressure shear velocities of the NAL and CF phases are obtained to be 5.601 ± 0.005 km/sec and 5.741 ± 0.001 km/sec, respectively. We also found that shear velocity increases by 2.5 % upon phase transition from NAL to CF at around 40 GPa.

  20. Thyroid hormone regulation of adult intestinal stem cells: Implications on intestinal development and homeostasis.

    PubMed

    Sun, Guihong; Roediger, Julia; Shi, Yun-Bo

    2016-12-01

    Organ-specific adult stem cells are essential for organ homeostasis, tissue repair and regeneration. The formation of such stem cells often takes place during postembryonic development, a period around birth in mammals when plasma thyroid hormone concentration is high. The life-long self-renewal of the intestinal epithelium has made mammalian intestine a valuable model to study the function and regulation and adult stem cells. On the other hand, much less is known about how the adult intestinal stem cells are formed during vertebrate development. Here, we will review some recent progresses on this subject, focusing mainly on the formation of the adult intestine during Xenopus metamorphosis. We will discuss the role of thyroid hormone signaling pathway in the process and potential molecular conservations between amphibians and mammals as well as the implications in organ homeostasis and human diseases.

  1. Olfactory epithelium: Cells, clinical disorders, and insights from an adult stem cell niche

    PubMed Central

    Choi, Rhea

    2018-01-01

    Disorders causing a loss of the sense of smell remain a therapeutic challenge. Basic research has, however, greatly expanded our knowledge of the organization and function of the olfactory system. This review describes advances in our understanding of the cellular components of the peripheral olfactory system, specifically the olfactory epithelium in the nose. The article discusses recent findings regarding the mechanisms involved in regeneration and cellular renewal from basal stem cells in the adult olfactory epithelium, considering the strategies involved in embryonic olfactory development and insights from research on other stem cell niches. In the context of clinical conditions causing anosmia, the current view of adult olfactory neurogenesis, tissue homeostasis, and failures in these processes is considered, along with current and future treatment strategies. Level of Evidence NA PMID:29492466

  2. Neuroinflammation and physical exercise as modulators of adult hippocampal neural precursor cell behavior.

    PubMed

    Pérez-Domínguez, Martha; Tovar-Y-Romo, Luis B; Zepeda, Angélica

    2018-01-26

    The dentate gyrus of the hippocampus is a plastic structure where adult neurogenesis constitutively occurs. Cell components of the neurogenic niche are source of paracrine as well as membrane-bound factors such as Notch, Bone Morphogenetic Proteins, Wnts, Sonic Hedgehog, cytokines, and growth factors that regulate adult hippocampal neurogenesis and cell fate decision. The integration and coordinated action of multiple extrinsic and intrinsic cues drive a continuous decision process: if adult neural stem cells remain quiescent or proliferate, if they take a neuronal or a glial lineage, and if new cells proliferate, undergo apoptotic death, or survive. The proper balance in the molecular milieu of this neurogenic niche leads to the production of neurons in a higher rate as that of astrocytes. But this rate changes in face of microenvironment modifications as those driven by physical exercise or with neuroinflammation. In this work, we first review the cellular and molecular components of the subgranular zone, focusing on the molecules, active signaling pathways and genetic programs that maintain quiescence, induce proliferation, or promote differentiation. We then summarize the evidence regarding the role of neuroinflammation and physical exercise in the modulation of adult hippocampal neurogenesis with emphasis on the activation of progression from adult neural stem cells to lineage-committed progenitors to their progeny mainly in murine models.

  3. Trospospheric degradation chemistry of HCFC-123 (CF 3CHCl 2): A proposed replacement chlorofluorocarbon

    NASA Astrophysics Data System (ADS)

    Hayman, G. D.; Jenkin, M. E.; Murrells, T. P.; Johnson, C. E.

    HCFC-123 has been proposed as a replacement for some of the fully halogenated chlorofluorocarbons and other chlorinated hydrocarbons, which are being phased out under the Montreal Protocol. This paper reports laboratory studies which were undertaken to determine kinetic and mechanistic parameters of reactions involved in the atmospheric degradation of HCFC-123 and the use of these parameters in a 2D global model of the troposphere to evaluate the yields of products formed in the degradation. The experimental studies have made use of the laser flash photolysis technique with time-resolved ultra-violet absorption spectroscopy for the kinetic measurements and broad-band ultra-violet absorption spectroscopy for product characterization. Rate coefficients have been determined for the self-reaction of CF 3CCl 2O 2 as (3.6±0.5)×10 -12 cm 3 mol -1 s -1 and for its reactions with HO 2 and NO as (1.9±0.7)×10 -12 cm 3 mol -1 s -1 and (1.5-2.0)×10 -11 cm 3 mol -1 s -1, respectively, at room temperature. Kinetic data have also been obtained for the reaction of CF 3CCl 2O 2 with C 2H 5O 2 and two channels have been identified; CF 3CCl 2+O 2+C 2H 5O 2→CF 3CCl 2O+C 2H 5O+ C 2H 5O+O 2, k=(9 +9-5)×10 13 cm 3 mol -1 s -1 and CF 3CCl 2O 2+C 2H 5O 2→CF 3CCl 2OH+CH 3CHO+O 2, k=(3.6±0.5)× 10 -12 cm 3 mol -1 s -1. Studies undertaken using the Cl-initiated oxidation of HCFC-123 suggest that trifluoroacetyl chloride, CF 3COCl, is the major product of the gas-phase degradation. The kinetic and mechanistic data have been used to formulate a chemical module of the degradation of HCFC-123 in the trophosphere. The module has been incorporated into a 2D model of the global troposphere so that the potential atmospheric impact of using HCFC-123 can be assessed.

  4. Fermentation products in the cystic fibrosis airways induce aggregation and dormancy-associated expression profiles in a CF clinical isolate of Pseudomonas aeruginosa.

    PubMed

    Phan, Joann; Gallagher, Tara; Oliver, Andrew; England, Whitney E; Whiteson, Katrine

    2018-05-01

    Pseudomonas aeruginosa is a well-known dominant opportunistic pathogen in cystic fibrosis (CF) with a wide range of metabolic capacities. However, P. aeruginosa does not colonize the airways alone, and benefits from the metabolic products of neighboring cells-especially volatile molecules that can travel between different parts of the airways easily. Here, we present a study that investigates the metabolic, gene expression profiles and phenotypic responses of a P. aeruginosa clinical isolate to fermentation products lactic acid and 2,3-butanediol, metabolites that are produced by facultative anaerobic members of the CF polymicrobial community and potential biomarkers of disease progression. Although previous studies have successfully investigated the metabolic and transcriptional profiles of P. aeruginosa, most have used common lab reference strains that may differ in important ways from clinical isolates. Using transcriptomics and metabolomics with gas chromatography time of flight mass spectrometry, we observe that fermentation products induce pyocyanin production along with the expression of genes involved in P. aeruginosa amino acid utilization, dormancy and aggregative or biofilm modes of growth. These findings have important implications for how interactions within the diverse CF microbial community influence microbial physiology, with potential clinical consequences.

  5. Glucocorticoids can affect Pseudomonas aeruginosa (ATCC 27853) internalization and intracellular calcium concentration in cystic fibrosis bronchial epithelial cells.

    PubMed

    Hussain, Rashida; Shahror, Rami; Karpati, Ferenc; Roomans, Godfried M

    2015-01-01

    Glucocorticoids (GCs) are anti-inflammatory agents, but their use in cystic fibrosis (CF) is controversial. In CF, the early colonization with Pseudomonas aeruginosa is mainly due to nonmucoid strains that can internalize, and induce apoptosis in the epithelial cells. Uptake of P. aeruginosa by the epithelial cells and subsequent apoptosis may prevent colonization of P. aeruginosa in CF airways. In the airway epithelia, several other biological effects, including an anti-secretory role by decreasing intracellular Ca(2+) concentration have been described for this anti-inflammatory drug. However, the effects of GCs on the nonmucoid P. aeruginosa internalization and intracellular Ca(2+) in CF bronchial epithelial cells have not been evaluated. We used cultured human CF bronchial airway epithelial cell (CFBE) monolayers to determine P. aeruginosa internalization, apoptosis, and intracellular Ca(2+)concentration in CF bronchial epithelial cells. Cells were treated with IL-6, IL-8, dexamethasone, betamethasone, or budesonide. GCs in co-treatments with IL-6 reversed the effect of IL-6 by decreasing the internalization of P. aeruginosa in the CFBE cells. GCs decreased the extent of apoptosis in CFBE cells infected with internalized P. aeruginosa, and increased the intracellular Ca(2+) concentration. These findings suggest that if internalization of P. aeruginosa reduces infection, GC therapy would increase the risk of pulmonary infection by decreasing the internalization of P. aeruginosa in CF cells, but GCs may improve airway hydration by increasing the intracellular Ca(2+) concentration. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out.

  6. Ethnic heterogeneity and cystic fibrosis transmembrane regulator (CFTR) mutation frequencies in Chicago-area CF families

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

    Ober, C.; Lester, L.A.; Mott, C.

    1992-12-01

    The identification of a common mutation, [Delta]F508, in the CFTR gene allowed, for the first time, the detection of cystic fibrosis (CF) carriers in the general population. Further genetic studies revealed >100 additional disease-causing mutations in this gene, few of which occur on >1% of CF chromosomes in any ethnic group. Prior to establishing counseling guidelines and carrier risk assessments, the authors sought to establish the frequencies of the CFTR mutations that are present in CF families living in the Chicago are, a region notable for its ethnic heterogeneity. Their sample included 283 unrelated CF carriers, with the following ethnicmore » composition: 78% non-Ashkenazi Caucasians, 5% Ashkenazi, 9% African-American, 3% Mexican, 0.3% Native American, and 5% mixed ancestry. When a panel of 10 mutations ([Delta]F508, [Delta]I507, G542X, G551D, R553X, S549N, R1162X, W1282X, N1303K, and 1717-1G[r arrow]A) was used, detection rates ranged from 75% in non-Ashkenazi Caucasians to 40% in African-Americans. These data suggest that the goal of screening for 90%-95% of CF mutations may be unrealistic in this and other, similar US populations. 22 refs., 1 tab.« less

  7. Cell-autonomous inactivation of the Reelin pathway impairs adult neurogenesis in the hippocampus

    PubMed Central

    Teixeira, Catia M.; Kron, Michelle M.; Masachs, Nuria; Zhang, Helen; Lagace, Diane C.; Martinez, Albert; Reillo, Isabel; Duan, Xin; Bosch, Carles; Pujadas, Lluis; Brunso, Lucas; Song, Hongjun; Eisch, Amelia J.; Borrell, Victor; Howell, Brian W.; Parent, Jack M.; Soriano, Eduardo

    2012-01-01

    Adult hippocampal neurogenesis is thought to be essential for learning and memory and has been implicated in the pathogenesis of several disorders. Although recent studies have identified key factors regulating neuroprogenitor proliferation in the adult hippocampus, the mechanisms that control the migration and integration of adult-born neurons into circuits are largely unknown. Reelin is an extracellular matrix protein that is vital for neuronal development. Activation of the Reelin cascade leads to phosphorylation of disabled-1 (Dab1), an adaptor protein required for Reelin signaling. Here we used transgenic mouse and retroviral reporters along with Reelin signaling gain- and loss-of-function studies to show that the Reelin pathway regulates migration and dendritic development of adult-generated hippocampal neurons. Whereas overexpression of Reelin accelerated dendritic maturation, inactivation of the Reelin signaling pathway specifically in adult neuroprogenitor cells resulted in aberrant migration, decreased dendrite development, formation of ectopic dendrites in the hilus and the establishment of aberrant circuits. Our findings support a cell-autonomous and critical role for the Reelin pathway in regulating dendritic development and the integration of adult-generated granule cells and point to this pathway as a key regulator of adult neurogenesis. Moreover, our data reveal a novel role of the Reelin cascade in adult brain function with potential implications for the pathogenesis of several neurological and psychiatric disorders. PMID:22933789

  8. Inhibition by TNF-alpha and IL-4 of cationic lipid mediated gene transfer in cystic fibrosis tracheal gland cells.

    PubMed

    Bastonero, Sonia; Gargouri, Myriem; Ortiou, Sandrine; Guéant, Jean-Louis; Merten, Marc D

    2005-11-01

    In vivo, tracheal gland serous cells highly express the cystic fibrosis transmembrane conductance regulator (cftr) gene. This gene is mutated in the lethal monogenic disease cystic fibrosis (CF). Clinical trials in which the human CFTR cDNA was delivered to the respiratory epithelia of CF patients have resulted in weak and transient gene expression. As CF is characterized by mucus inspissation, airway infection, and severe inflammation, we tested the hypothesis that inflammation and especially two cytokines involved in the Th1/Th2 inflammatory response, interleukin 4 (IL-4) and TNFalpha, could inhibit gene transfer efficiency using a model of human CF tracheal gland cells (CF-KM4) and Lipofectamine reagent as a transfection reagent. The specific secretory defects of CF-KM4 cells were corrected by Lipofectamine-mediated human CFTR gene transfer. However, this was altered when cells were pre-treated with IL-4 and TNFalpha. Inhibition of luciferase reporter gene expression by IL-4 and TNFalpha pre-treated CF-KM4 cells was measured by activity and real-time RT-PCR. Both cytokines induced similar and synergistic inhibition of transgene expression and activity. This cytokine-mediated inhibition could be prevented by anti-inflammatory agents such as glucocorticoids but not by non-steroidal (NSAI) agents. This data suggests that an inflammatory context generated by IL-4 and TNFalpha can inhibit human CFTR gene transfer in CF tracheal gland cells and that glucocorticoids may have a protecting action. Copyright (c) 2005 John Wiley & Sons, Ltd.

  9. CF60 Concrete Composition Design and Application on Fudiankou Xijiang Super Large Bridge

    NASA Astrophysics Data System (ADS)

    Qiu, Yi Mei; Wen, Sen Yuan; Chen, Jun Xiang

    2018-06-01

    Guangxi Wuzhou City Ring Road Fudiankou Xijiang super large bridge CF60 concrete is a new multi-phase composite high-performance concrete, this paper for the Fudiankou Xijiang bridge structure and characteristics of the project, in accordance with the principle of local materials and technical specification requirements, combined with the site conditions of CF60 engineering high performance concrete component materials, proportion and the technical performance, quantify the main physical and mechanical performance index. Analysis main influencing factors of the technical indicators, reasonable adjustment of concrete mix design parameters, and the use of technical means of admixture and multi-function composite admixture of concrete, obtain the optimal proportion of good work, process, mechanical properties stability and durability of engineering properties, recommend and verification of concrete mix; to explore the CF60 high performance concrete Soil in the Fudiankou Xijiang bridge application technology, detection and tracking the quality of concrete construction, concrete structure during the construction of the key technology and control points is proposed, evaluation of CF60 high performance concrete in the actual engineering application effect and benefit to ensure engineering quality of bridge structure and service life, and super long span bridge engineering construction to provide basis and reference.

  10. Outcomes of intensive care unit care in adults with cystic fibrosis.

    PubMed

    Sood, N; Paradowski, L J; Yankaskas, J R

    2001-02-01

    Cystic fibrosis (CF) causes progressive respiratory failure and death in more than 90% of patients. Mechanical ventilation has been discouraged in CF because of poor outcomes, but improved survival and the availability of lung transplantation have increased the indications for care of CF patients in the intensive care unit (ICU). We studied the outcomes of all CF patients admitted to the University of North Carolina Hospitals Medical ICU from January 1990 through December 1998. Seventy-six patients, ranging in ages from 17 to 45 yr (mean: 27 yr), and of whom 53% were female, had 136 admissions for exacerbations of CF with respiratory failure (RF, n = 65), hemoptysis (n = 33), antibiotic desensitization (n = 30), pneumothorax (n = 3), or other reasons (n = 5). Eighty-six percent of the patients with hemoptysis and all of those with desensitization and pneumothorax were alive 1 yr after ICU discharge. Of the 42 patients with RF, 37 (88%) required assisted ventilation. Twenty-three (55%) of the patients with RF survived to ICU discharge and 19 (45%) died. Seventeen (40%) of the patients with RF received lung transplants and 14 were alive 1 yr later. Without transplantation, three (7%) of the patients with RF were alive and three (7%) were dead 1 yr later. Sex, body mass index, and respiratory bacteria did not correlate with survival. We conclude that ICU care for adults with CF who have reversible complications is appropriate and effective. Ventilatory support is appropriate for some transplant candidates.

  11. ULTRASTRUCTURAL CHARACTERIZATION OF THE LYTIC CYCLE OF AN INTRANUCLEAR VIRUS INFECTING THE DIATOM CHAETOCEROS CF. WIGHAMII(BACILLARIOPHYCEAE) FROM CHESAPEAKE BAY, USA(1).

    PubMed

    Eissler, Yoanna; Wang, Kui; Chen, Feng; Eric Wommack, K; Wayne Coats, D

    2009-08-01

    Numerous microalgal species are infected by viruses that have the potential to control phytoplankton dynamics by reducing host populations, preventing bloom formation, or causing the collapse of blooms. Here we describe a virus infecting the diatom Chaetoceros cf. wighamii Brightw. from the Chesapeake Bay. To characterize the morphology and lytic cycle of this virus, we conducted a time-course experiment, sampling every 4 h over 72 h following viral inoculation. In vivo fluorescence began to decline 16 h after inoculation and was reduced to <19% of control cultures by the end of experiment. TEM confirmed infection within the first 8 h of inoculation, as indicated by the presence of virus-like particles (VLP) in the nuclei. VLP were present in two different arrangements: rod-like structures that appeared in cross-section as paracrystalline arrays of hexagonal-shaped profiles measuring 12 ± 2 nm in diameter and uniformly electron-dense hexagonal-shaped particles measuring ∼ 22-28 nm in diameter. Nuclei containing paracrystalline arrays were most prevalent early in the infection cycle, while cells containing VLP increased and then declined toward the end of the cycle. The proportion of nuclei containing both paracrystalline arrays and VLP remained relatively constant. This pattern suggests that rod-like paracrystalline arrays fragmented to produce icosahedral VLP. C. cf. wighamii nuclear inclusion virus (CwNIV) is characterized by a high burst size (averaged 26,400 viruses per infected cell) and fast generation time that could have ecological implications on C. cf. wighamii population control. © 2009 Phycological Society of America.

  12. Kinetics of the Reaction of O((sup 3)P) with CF3NO

    NASA Technical Reports Server (NTRS)

    Thorn, R. P.; Nicovich, J. M.; Cronkhite, J. M.; Wine, P. H.

    1997-01-01

    A laser flash photolysis-resonance fluorescence technique has been employed to study the kinetics of the reaction of O((sup 3)P) with CF3NO (k(2)) as a function of temperature. Our results are described by the Arrhenius expression k(2)(T) = (4.54 +/- 0.70) x 10(exp -l2)exp[(-560 +/- 46)/T] cu cm/molecule.s (243 K is less than or equal to T is less than or equal to 424 K); errors are 2 sigma and represent precision only. The O((sup 3)P) + CF3NO reaction is sufficiently rapid that CF3NO cannot be employed as a selective quencher for O2(alpha(1) Delta-g) in laboratory systems where O((sup 3)P) and O2(alpha 1 Delta g) coexist, and where O((sup 3)P) kinetics are being investigated.

  13. PARP activity and inhibition in fetal and adult oligodendrocyte precursor cells: Effect on cell survival and differentiation.

    PubMed

    Baldassarro, Vito A; Marchesini, Alessandra; Giardino, Luciana; Calzà, Laura

    2017-07-01

    Poly (ADP-ribose) polymerase (PARP) family members are ubiquitously expressed and play a key role in cellular processes, including DNA repair and cell death/survival balance. Accordingly, PARP inhibition is an emerging pharmacological strategy for cancer and neurodegenerative diseases. Consistent evidences support the critical involvement of PARP family members in cell differentiation and phenotype maturation. In this study we used an oligodendrocyte precursor cells (OPCs) enriched system derived from fetal and adult brain to investigate the role of PARP in OPCs proliferation, survival, and differentiation. The PARP inhibitors PJ34, TIQ-A and Olaparib were used as pharmacological tools. The main results of the study are: (i) PARP mRNA expression and PARP activity are much higher in fetal than in adult-derived OPCs; (ii) the culture treatment with PARP inhibitors is cytotoxic for OPCs derived from fetal, but not from adult, brain; (iii) PARP inhibition reduces cell number, according to the inhibitory potency of the compounds; (iv) PARP inhibition effect on fetal OPCs is a slow process; (v) PARP inhibition impairs OPCs maturation into myelinating OL in fetal, but not in adult cultures, according to the inhibitory potency of the compounds. These results have implications for PARP-inhibition therapies for diseases and lesions of the central nervous system, in particular for neonatal hypoxic/ischemic encephalopathy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. REVIEW OF INDEPENDENT NURSE PRESCRIBING IN A PAEDIATRIC CYSTIC FIBROSIS (CF) AND RESPIRATORY POPULATION.

    PubMed

    Chana, Gabis; Tabberner, Michelle; Nixon, Wendy; Frost, Sue; Barrett, Leslie; Desai, Maya; Paskin, Lucy

    2016-09-01

    With pressures on junior doctors' availability in the NHS, non-medical prescribing is topical. Independent Nurse Prescribers (INPs) can prescribe any licensed medicine for any medical condition within their level of competence.1 An audit was undertaken of the four INPs employed by the Respiratory Department evaluating current prescribing practices. The requirement for this audit was identified by the multidisciplinary team (MDT) and Trust approval was obtained. A data collection form was designed capturing patient demographics and full details of prescribed items.Over a 3 month period (August to October 2014) outpatient cystic fibrosis (CF) and respiratory prescriptions were studied using cluster sampling. Over a 6 week period prescription requests by CF INPs faxed to General Practitioners (GPs) were reviewed. INPs also prescribe via telephone, documenting advice on trust forms; these were preliminarily audited. All data was analysed using Microsoft Excel. Legality of prescriptions and adherence to national and local guidelines were evaluated. Reference keys were used to designate non-adherence post-application of exclusion criteria. A total of 77 outpatient prescriptions (45 CF and 32 respiratory) were completed by the 4 INPs, containing 122 items (72 CF and 50 respiratory). Of the CF prescribed items 21 were oral antibiotics (29%). Respiratory INPs mainly prescribed 14 inhaler devices (28%) and 12 inhaled bronchodilators (24%).All INP prescriptions met legal requirements. Basic details of medicinal products (drug name and dose) were documented for all items. A key finding was that duration/quantity was not indicated for 27 (54%) respiratory items.After applying exclusion criteria, of the CF prescribed items, 56/59 (95%) adhered to national guidelines and 47/66 (71%) followed local guidelines. The leading reason for not following local guidelines was not documenting allergy status. Of the respiratory prescribed items, 34 (100%) adhered to national guidelines and

  15. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

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

    Park, Kyoung Ho; Yeo, Sang Won, E-mail: swyeo@catholic.ac.kr; Troy, Frederic A., E-mail: fatroy@ucdavis.edu

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC withmore » epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.« less

  16. Correlates of Segmental Pulse Wave Velocity in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study.

    PubMed

    Meyer, Michelle L; Tanaka, Hirofumi; Palta, Priya; Cheng, Susan; Gouskova, Natalia; Aguilar, David; Heiss, Gerardo

    2016-01-01

    Carotid-femoral PWV (cfPWV) is a well-established measure of central arterial stiffness, while brachial-ankle PWV (baPWV) is being used more frequently in East Asian countries. Few studies have simultaneously characterized the distributions and correlates of segment-specific PWV measures and their associations with cardiovascular risk factors. We evaluated segment-specific PWV (cfPWV, baPWV, and femoral-ankle (faPWV)) in 4,974 older-aged African American and Caucasian adults in the community-based Atherosclerosis Risk in Communities (ARIC) Study using a standardized protocol and the OMRON VP-1000 Plus system. We examined the distribution and multivariable-adjusted correlates of PWV measures by race and sex. Mean age ranged from 74 ± 5 to 76 ± 5 years across race-sex groups. In all race-sex groups, cfPWV correlated with baPWV but not with faPWV, and cfPWV and baPWV were higher with age, whereas faPWV was not. Heart rate and systolic blood pressure (SBP) were positively associated and weight was negatively associated with all PWV measures; however, the associations with age, glycated hemoglobin, triglycerides, and high-density lipoprotein (HDL) cholesterol varied by segment and race-sex group. Our findings indicate that cfPWV and faPWV reflect distinct aspects of segment-specific vascular stiffness and their associated profile of cardiovascular risk factors. Even among older adults, age is associated with higher cfPWV and baPWV, but not with faPWV. Understanding factors that ostensibly play a role in increasing arterial stiffness in different arterial territories can inform opportunities for cardiovascular disease (CVD) prevention and risk management. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Cascade filtration (CF) with the Haemonetics MCS+: a new technical adaptation.

    PubMed

    Valbonesi, M; Bo, A; De Luigi, M C; Bruni, R; Stura, P; Sanfilippo, B; Varinelli, I

    2001-03-01

    CF was introduced in clinical medicine in 1980. Up to now, exclusively two-vein procedures have been carried out with some limitations to expansion of this technique. In this report we describe the very first application of single-needle CF carried out with Haemonetics MCS + apparatus. Twenty procedures were completed without any untoward effect in patients suffering from TTP, post-hepatitic cryoblobulinemia, familial hypercholesterolemia and acute Guillan-Barrè Syndrome. From 1 to 4 sessions were carried out per patient with the expected laboratory and clinical results. The only limit is the procedure time that averages 231 +/- 48 min., approximately 40% longer than two needle procedures.

  18. CF6 Jet Engine Diagnostics Program: High pressure compressor clearance investigation

    NASA Technical Reports Server (NTRS)

    Radomski, M. A.

    1982-01-01

    The effects of high pressure compressor clearance changes on engine performance were experimentally determined on a CF6 core engine. The results indicate that a one percent reduction in normalized average clearance, expressed as a fraction of airfoil length, improves compressor efficiency by one percent. Compressor clearances are reduced by the application of rotor bore cooling, insulation of the stator casing, and use of a low coefficient of expansion material in the aft stages. This improvement amounts to a reduction of normalized average clearance of 0.78 percent, relative to CF6-60 compressor, which is equivalent to an improvement in compressor efficiency of 0.78 percent.

  19. Correlation of Streptococcus mutans and Streptococcus sanguinis colonization and ex vivo hydrogen peroxide production in carious lesion-free and high caries adults.

    PubMed

    Giacaman, Rodrigo A; Torres, Sebastián; Gómez, Yenifer; Muñoz-Sandoval, Cecilia; Kreth, Jens

    2015-01-01

    This study was conducted to estimate oral colonization by Streptococcus mutans and Streptococcus sanguinis in adults with high and without any caries experience. Furthermore, differences in the amount of hydrogen peroxide (H2O2) produced by S. sanguinis isolated from both groups were assessed. Forty adults were divided into: (i) carious lesion-free, without any carious lesion, assessed by the International Caries Detection and Assessment System (ICDAS), or restoration, (CF) and (ii) high caries experience (HC). Saliva samples were collected and seeded on respective agar-plates for enumeration of total streptococci, S. mutans and S. sanguinis (CFU/mL) and compared between groups. Additionally, S. sanguinis colonies obtained from both groups were inoculated on Prussian blue agar for H2O2 detection. Production of H2O2 was quantified and compared between the two groups. S. sanguinis counts were significantly higher in CF than HC individuals (p<0.05). Conversely, S. mutans showed significantly higher levels in HC than CF subjects (p<0.001). S. sanguinis colonies from CF individuals produced significantly larger H2O2 halos compared with HC subjects. S. sanguinis predominates over S. mutans in saliva of adults without caries experience. In those people, S. sanguinis produces more H2O2ex vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Mechanisms of reduced susceptibility and genotypic prediction of antibiotic resistance in Prevotella isolated from cystic fibrosis (CF) and non-CF patients

    PubMed Central

    Sherrard, Laura J.; Schaible, Bettina; Graham, Kathryn A.; McGrath, Stef J.; McIlreavey, Leanne; Hatch, Joseph; Wolfgang, Matthew C.; Muhlebach, Marianne S.; Gilpin, Deirdre F.; Schneiders, Thamarai; Elborn, J. Stuart; Tunney, Michael M.

    2014-01-01

    Objectives To investigate mechanisms of reduced susceptibility to commonly used antibiotics in Prevotella cultured from patients with cystic fibrosis (CF), patients with invasive infection and healthy control subjects and to determine whether genotype can be used to predict phenotypic resistance. Methods The susceptibility of 157 Prevotella isolates to seven antibiotics was compared, with detection of resistance genes (cfxA-type gene, ermF and tetQ), mutations within the CfxA-type β-lactamase and expression of efflux pumps. Results Prevotella isolates positive for a cfxA-type gene had higher MICs of amoxicillin and ceftazidime compared with isolates negative for this gene (P < 0.001). A mutation within the CfxA-type β-lactamase (Y239D) was associated with ceftazidime resistance (P = 0.011). The UK CF isolates were 5.3-fold, 2.7-fold and 5.7-fold more likely to harbour ermF compared with the US CF, UK invasive and UK healthy control isolates, respectively. Higher concentrations of azithromycin (P < 0.001) and clindamycin (P < 0.001) were also required to inhibit the growth of the ermF-positive isolates compared with ermF-negative isolates. Furthermore, tetQ-positive Prevotella isolates had higher MICs of tetracycline (P = 0.001) and doxycycline (P < 0.001) compared with tetQ-negative isolates. Prevotella spp. were also shown, for the first time, to express resistance nodulation division (RND)-type efflux pumps. Conclusions This study has demonstrated that Prevotella isolated from various sources harbour a common pool of resistance genes and possess RND-type efflux pumps, which may contribute to tetracycline resistance. The findings indicate that antibiotic resistance is common in Prevotella spp., but the genotypic traits investigated do not reflect phenotypic antibiotic resistance in every instance. PMID:24917582

  1. Establishment of cell lines from adult T-cell leukemia cells dependent on negatively charged polymers.

    PubMed

    Kagami, Yoshitoyo; Uchiyama, Susumu; Kato, Harumi; Okada, Yasutaka; Seto, Masao; Kinoshita, Tomohiro

    2017-07-05

    Growing adult T-cell leukemia/lymphoma (ATLL) cells in vitro is difficult. Here, we examined the effects of static electricity in the culture medium on the proliferation of ATLL cells. Six out of 10 ATLL cells did not proliferate in vitro and thus had to be cultured in a medium containing negatively charged polymers. In the presence of poly-γ-glutamic acid (PGA) or chondroitin sulfate (CDR), cell lines (HKOX3-PGA, HKOX3-CDR) were established from the same single ATLL case using interleukin (IL)-2, IL-4, and feeder cells expressing OX40L (OX40L + HK). Dextran sulfate inhibited growth in both HKOX3 cell lines. Both PGA and OX40L + HK were indispensable for HKOX3-PGA growth, but HKOX3-CDR could proliferate in the presence of CDR or OX40L + HK alone. Thus, the specific action of each negatively charged polymer promoted the growth of specific ATLL cells in vitro.

  2. Continuous application of compressive force induces fusion of osteoclast-like RAW264.7 cells via upregulation of RANK and downregulation of LGR4.

    PubMed

    Matsuike, Rieko; Tanaka, Hideki; Nakai, Kumiko; Kanda, Mai; Nagasaki, Maki; Murakami, Fumiko; Shibata, Chika; Mayahara, Kotoe; Nakajima, Akira; Tanabe, Natsuko; Kawato, Takayuki; Maeno, Masao; Shimizu, Noriyoshi

    2018-05-15

    During orthodontic treatment, facilitating osteoclastic bone resorption in the alveolar bone exposed to the compressive force (CF) is an important factor for tooth movement. The present study investigated the effect of CF stimulation on the differentiation of RAW264.7 cells from precursors to mature osteoclasts. The cells were continuously stimulated with 0.3, 0.6, or 1.1 g/cm 2 CF-which was generated by increasing the volume of culture medium in the wells of a 96-well plate-in the presence or absence of receptor activator of nuclear factor κB (RANK) ligand (RANKL) for 4 days. In the presence of RANKL, the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and the mRNA levels of dendritic cell-specific transmembrane protein (DC-STAMP) and osteoclast-stimulatory transmembrane protein (OC-STAMP) were increased by application of 0.6 and 1.1 g/cm 2 CF as compared to 0.3 g/cm 2 CF. The mRNA level of RANK was upregulated whereas that of leucine-rich repeat-containing G-protein-coupled receptor (LGR)4-another RANKL receptor was downregulated by 0.6 and 1.1 g/cm 2 CF as compared to 0.3 g/cm 2 CF in the absence of RANKL. The proportion of cells with nuclear translocation of the nuclear translocation of nuclear factor of activated T cells (NFAT)c1 was increased by 0.6 and 1.1 g/cm 2 CF in the presence of RANKL. Continuous application of CF induced the differentiation of RAW264.7 cells into TRAP-positive multinuclear cells by enhancing the expression of DC- and OC-STAMP and the nuclear translocation of NFATc1. This may result from the CF-induced increase in RANK and decrease in LGR4 expression. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Cell-type-specific expression of NFIX in the developing and adult cerebellum.

    PubMed

    Fraser, James; Essebier, Alexandra; Gronostajski, Richard M; Boden, Mikael; Wainwright, Brandon J; Harvey, Tracey J; Piper, Michael

    2017-07-01

    Transcription factors from the nuclear factor one (NFI) family have been shown to play a central role in regulating neural progenitor cell differentiation within the embryonic and post-natal brain. NFIA and NFIB, for instance, promote the differentiation and functional maturation of granule neurons within the cerebellum. Mice lacking Nfix exhibit delays in the development of neuronal and glial lineages within the cerebellum, but the cell-type-specific expression of this transcription factor remains undefined. Here, we examined the expression of NFIX, together with various cell-type-specific markers, within the developing and adult cerebellum using both chromogenic immunohistochemistry and co-immunofluorescence labelling and confocal microscopy. In embryos, NFIX was expressed by progenitor cells within the rhombic lip and ventricular zone. After birth, progenitor cells within the external granule layer, as well as migrating and mature granule neurons, expressed NFIX. Within the adult cerebellum, NFIX displayed a broad expression profile, and was evident within granule cells, Bergmann glia, and interneurons, but not within Purkinje neurons. Furthermore, transcriptomic profiling of cerebellar granule neuron progenitor cells showed that multiple splice variants of Nfix are expressed within this germinal zone of the post-natal brain. Collectively, these data suggest that NFIX plays a role in regulating progenitor cell biology within the embryonic and post-natal cerebellum, as well as an ongoing role within multiple neuronal and glial populations within the adult cerebellum.

  4. Horizontal transmission of Symbiodinium cells between adult and juvenile corals is aided by benthic sediment

    NASA Astrophysics Data System (ADS)

    Nitschke, Matthew R.; Davy, Simon K.; Ward, Selina

    2016-03-01

    Of all reef-building coral species, 80-85 % initially draw their intracellular symbionts (dinoflagellates of the genus Symbiodinium) from the environment. Although Symbiodinium cells are crucial for the growth of corals and the formation of coral reefs, little is known about how corals first encounter free-living Symbiodinium cells. We report how the supply of free-living Symbiodinium cells to the benthos by adult corals can increase the rate of horizontal symbiont acquisition for conspecific recruits. Three species of newly settled aposymbiotic (i.e., symbiont-free) corals were maintained in an open aquarium system containing: sterilized sediment and adult coral fragments combined; adult coral fragments alone; sterilized sediment alone; or seawater at Heron Island, Great Barrier Reef, Australia. In all instances, the combination of an adult coral and sediment resulted in the highest symbiont acquisition rates by juvenile corals (up to five-fold greater than seawater alone). Juvenile corals exposed to individual treatments of adult coral or sediment produced an intermediate acquisition response (<52 % of recruits), and symbiont acquisition from unfiltered seawater was comparatively low (<20 % of recruits). Additionally, benthic free-living Symbiodinium cells reached their highest densities in the adult coral + sediment treatment (up to 1.2 × 104 cells mL-1). Our results suggest that corals seed microhabitats with free-living Symbiodinium cells suitable for many coral species during the process of coral recruitment.

  5. Duplication in CHIT1 gene and the risk for Aspergillus lung disease in CF patients.

    PubMed

    Livnat, Galit; Bar-Yoseph, Ronen; Mory, Adi; Dagan, Efrat; Elias, Nael; Gershoni, Ruth; Bentur, Lea

    2014-01-01

    Aspergillus often persists in the respiratory tract of patients with Cystic Fibrosis (CF) and may cause allergic broncho-pulmonary aspergillosis (ABPA). Chitinases are enzymes that digest the chitin polymer. Plants use chitinase as a defense mechanism against fungi. Chitotriosidase (CHIT1) is the major chitinase in human airways. Variation in the coding region with 24-bp duplication allele results in reduced CHIT1 activity. Recently, CHIT1 duplication heterozygocity was found in 6/6 patients with severe asthma and fungal sensitization (SAFS). Our aim was to evaluate the link between CHIT1 duplication in CF patients and the predisposition to Allergic broncho-pulmonary mycosis (ABPM) or persistent Aspergillus positive sputum (APS). CHIT1 duplication was assessed in three CF groups. Group 1: patients who had neither ABPM nor APS in the past (control group). Group 2: patients with persistent APS (≥2/year), without ABPA. Group 3: patients with current or past ABPM. Forty patients with CF were included in the analysis, CHIT1 duplication heterozygocity was found in 3/6 (50%) of the patients in the ABPM group, 3/12 (25%) in the APS group, and 7/22 (31.8%) in the control group (P > 0.05). Eleven patients carried W1282X mutation, 90.9% were negative for CHIT1 duplication, five of them were homozygous for W1282X; none of them had CHIT1 duplication or ABPM. CHIT1 duplication is not found in all CF patients with ABPM in contrast to patients with SAFS. These results suggest that CHIT1 duplication cannot be the sole explanation for Aspergillus positive sputum in CF patients. © 2013 Wiley Periodicals, Inc.

  6. Wnt Protein-mediated Satellite Cell Conversion in Adult and Aged Mice Following Voluntary Wheel Running

    PubMed Central

    Fujimaki, Shin; Hidaka, Ryo; Asashima, Makoto; Takemasa, Tohru; Kuwabara, Tomoko

    2014-01-01

    Muscle represents an abundant, accessible, and replenishable source of adult stem cells. Skeletal muscle-derived stem cells, called satellite cells, play essential roles in regeneration after muscle injury in adult skeletal muscle. Although the molecular mechanism of muscle regeneration process after an injury has been extensively investigated, the regulation of satellite cells under steady state during the adult stage, including the reaction to exercise stimuli, is relatively unknown. Here, we show that voluntary wheel running exercise, which is a low stress exercise, converts satellite cells to the activated state due to accelerated Wnt signaling. Our analysis showed that up-regulated canonical Wnt/β-catenin signaling directly modulated chromatin structures of both MyoD and Myf5 genes, resulting in increases in the mRNA expression of Myf5 and MyoD and the number of proliferative Pax7+Myf5+ and Pax7+ MyoD+ cells in skeletal muscle. The effect of Wnt signaling on the activation of satellite cells, rather than Wnt-mediated fibrosis, was observed in both adult and aged mice. The association of β-catenin, T-cell factor, and lymphoid enhancer transcription factors of multiple T-cell factor/lymphoid enhancer factor regulatory elements, conserved in mouse, rat, and human species, with the promoters of both the Myf5 and MyoD genes drives the de novo myogenesis in satellite cells even in aged muscle. These results indicate that exercise-stimulated extracellular Wnts play a critical role in the regulation of satellite cells in adult and aged skeletal muscle. PMID:24482229

  7. SITE DEMONSTRATION OF THE CF SYSTEMS ORGANIC EXTRACTION PROCESS

    EPA Science Inventory

    The CF Systems Organic Extraction Process was used to remove PCBs from contaminated sediment dredged from the New Bedford Harbor. This work was done as part of a field demonstration under EPA's Superfund Innovative Technology Evaluation (SITE) program. The purpose of the SITE p...

  8. Measurement of prompt fission neutron spectrum for spontaneous fission of 252Cf using γ multiplicity tagging

    NASA Astrophysics Data System (ADS)

    Blain, E.; Daskalakis, A.; Block, R. C.; Danon, Y.

    2017-06-01

    The prompt fission neutron spectrum from spontaneous fission of 252Cf is an integral part of several aspects of nuclear data. Not only is the spectrum itself of interest, but neutron detectors often use the spectrum for calibration, and other prompt fission neutron spectra are measured as a ratio to 252Cf. Therefore, reducing the uncertainties in this spectrum will allow for more accurate nuclear data to be available across a wide range of fields. The prompt fission neutron spectrum for the spontaneous fission of 252Cf was measured at Rensselaer Polytechnic Institute using the multiple γ tagging method with a 18.4-ng fission sample. An EJ-301 liquid scintillator fast neutron detector was used to measure the high energy portion of the spectrum, 0.5-7 MeV, and a thin EJ-204 plastic scintillator was used to measure the low energy portion of the spectrum, from 50 keV to 2 MeV. These spectra both show good agreement with the current evaluation of 252Cf and have low associated uncertainties providing a new high precision measurement that helps reduce the uncertainties in the prompt fission neutron spectrum for the spontaneous fission of 252Cf.

  9. Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells

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

    Poghosyan, Anna, E-mail: pannagos@yahoo.com; Patel, Jamie K.; Clifford, Rachel L.

    Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show abnormal epigenetic regulation is responsible for CXCL8 overexpression in CF cells. Under basal conditions CF cells had increased bromodomain (Brd)3 and Brd4 recruitment and enhanced NF-κB and C/EBPβ binding to the CXCL8 promoter compared to non-CF cells due to trimethylation of histone H3 at lysine 4 (H3K4me3) and DNA hypomethylation at CpG6. IL-1β increased NF-κB, C/EBPβ and Brd4 binding. Furthermore, inhibitors ofmore » bromodomain and extra-terminal domain family (BET) proteins reduced CXCL8 production in CF cells suggesting a therapeutic target for the BET pathway. -- Highlights: •A regulatory mechanism of CXCL8 transcriptional control in CF airways is proposed. •There was an increased binding of NF-κB and C/EBPβ transcription factors. •There was enhanced recruitment of BET proteins to the CXCL8 promoter. •Epigenetic modifications are responsible for the aberrant CXCL8 transcription.« less

  10. A Cell Number Counting Factor Regulates Akt/Protein Kinase B To Regulate Dictyostelium discoideum Group Size

    PubMed Central

    Gao, Tong; Knecht, David; Tang, Lei; Hatton, R. Diane; Gomer, Richard H.

    2004-01-01

    Little is known about how individual cells can organize themselves to form structures of a given size. During development, Dictyostelium discoideum aggregates in dendritic streams and forms groups of ∼20,000 cells. D. discoideum regulates group size by secreting and simultaneously sensing a multiprotein complex called counting factor (CF). If there are too many cells in a stream, the associated high concentration of CF will decrease cell-cell adhesion and increase cell motility, causing aggregation streams to break up. The pulses of cyclic AMP (cAMP) that mediate aggregation cause a transient translocation of Akt/protein kinase B (Akt/PKB) to the leading edge of the plasma membrane and a concomitant activation of the kinase activity, which in turn stimulates motility. We found that countin− cells (which lack bioactive CF) and wild-type cells starved in the presence of anticountin antibodies (which block CF activity) showed a decreased level of cAMP-stimulated Akt/PKB membrane translocation and kinase activity compared to parental wild-type cells. Recombinant countin has the bioactivity of CF, and a 1-min treatment of cells with recombinant countin potentiated Akt/PKB translocation to membranes and Akt/PKB activity. Western blotting of total cell lysates indicated that countin does not affect the total level of Akt/PKB. Fluorescence microscopy of cells expressing an Akt/PKB pleckstrin homology domain-green fluorescent protein (PH-GFP) fusion protein indicated that recombinant countin and anti-countin antibodies do not obviously alter the distribution of Akt/PKB PH-GFP when it translocates to the membrane. Our data indicate that CF increases motility by potentiating the cAMP-stimulated activation and translocation of Akt/PKB. PMID:15470246

  11. Ablation of proliferating neural stem cells during early life is sufficient to reduce adult hippocampal neurogenesis.

    PubMed

    Youssef, Mary; Krish, Varsha S; Kirshenbaum, Greer S; Atsak, Piray; Lass, Tamara J; Lieberman, Sophie R; Leonardo, E David; Dranovsky, Alex

    2018-05-09

    Environmental exposures during early life, but not during adolescence or adulthood, lead to persistent reductions in neurogenesis in the adult hippocampal dentate gyrus (DG). The mechanisms by which early life exposures lead to long-term deficits in neurogenesis remain unclear. Here, we investigated whether targeted ablation of dividing neural stem cells during early life is sufficient to produce long-term decreases in DG neurogenesis. Having previously found that the stem cell lineage is resistant to long-term effects of transient ablation of dividing stem cells during adolescence or adulthood (Kirshenbaum et al., 2014), we used a similar pharmacogenetic approach to target dividing neural stem cells for elimination during early life periods sensitive to environmental insults. We then assessed the Nestin stem cell lineage in adulthood. We found that the adult neural stem cell reservoir was depleted following ablation during the first postnatal week, when stem cells were highly proliferative, but not during the third postnatal week, when stem cells were more quiescent. Remarkably, ablating proliferating stem cells during either the first or third postnatal week led to reduced adult neurogenesis out of proportion to the changes in the stem cell pool, indicating a disruption of the stem cell function or niche following stem cell ablation in early life. These results highlight the first three postnatal weeks as a series of sensitive periods during which elimination of dividing stem cells leads to lasting alterations in adult DG neurogenesis and stem cell function. These findings contribute to our understanding of the relationship between DG development and adult neurogenesis, as well as suggest a possible mechanism by which early life experiences may lead to lasting deficits in adult hippocampal neurogenesis. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  12. Compressive force induces osteoclast differentiation via prostaglandin E(2) production in MC3T3-E1 cells.

    PubMed

    Sanuki, Rina; Shionome, Chieko; Kuwabara, Akiko; Mitsui, Narihiro; Koyama, Yuki; Suzuki, Naoto; Zhang, Fan; Shimizu, Noriyoshi; Maeno, Masao

    2010-04-01

    In orthodontic tooth movement, prostaglandin E(2) (PGE(2)) released from osteoblasts can alter the normal process of bone remodeling. We previously showed that compressive force (CF) controls bone formation by stimulating the production of PGE(2) and Ep2 and/or Ep4 receptors in osteoblasts. The present study was undertaken to examine the effect of CF on the production of PGE(2), cyclooxygenase-2 (COX-2), macrophage colony-stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) using osteoblastic MC3T3-E1 cells and to examine the indirect effect of CF on osteoclast differentiation using RAW264.7 cells as osteoclast precursors. MC3T3-E1 cells were cultured with or without continuous CF (1.0 or 3.0 g/cm(2)) for 24 hr, and PGE(2) production was determined using ELISA. The expression of COX-2, M-CSF, RANKL, and OPG genes and proteins was determined using real-time PCR and ELISA, respectively. Osteoclast differentiation was estimated using tartrate-resistant acid phosphatase (TRAP) staining of RAW 264.7 cells cultured for 10 days with conditioned medium from CF-treated MC3T3-E1 cells and soluble RANKL. As CF increased, PGE(2) production and the expression of COX-2, M-CSF, and RANKL increased, whereas OPG expression decreased. The number of TRAP-positive cells increased as CF increased. Celecoxib, a specific inhibitor of COX-2, blocked the stimulatory effect of CF on TRAP staining and the production of PGE(2), M-CSF, RANKL, and OPG. These results suggest that CF induces osteoclast differentiation by increasing M-CSF production and decreasing OPG production via PGE(2) in osteoblasts.

  13. Occurrence of Pseudomonas aeruginosa in waters: implications for patients with cystic fibrosis (CF).

    PubMed

    Caskey, S; Stirling, J; Moore, J E; Rendall, J C

    2018-06-01

    Chronic Pseudomonas aeruginosa infection is associated with increased morbidity and mortality in patients with cystic fibrosis (CF). Current understanding of risk factors for acquisition is limited and so the aim of this study was to examine a large sample of environmental waters from diverse sources. Environmental water samples (n = 7904) from jacuzzis, hydrants, swimming pools, hot tubs, plunge pools, bottled natural mineral water, taps, springs, ice machines, water coolers, bores and showers were examined for the presence of P. aeruginosa. Pseudomonas aeruginosa was detected in 524/7904 (6·6%) waters examined. Hot tubs (51/243; 20·9%), tap water (3/40; 8%) and jacuzzis (432/5811; 7·4%) were the most likely environments where P. aeruginosa was isolated. Pseudomonas aeruginosa was isolated from bottled water (2/67; 3%). Our study highlights the ubiquitous nature of P. aeruginosa in the environment. Given CF patients are frequently counselled to make lifestyle changes to minimize P. aeruginosa exposure, these results have important implications. In particular, the occurrence of P. aeruginosa in tap water highlights the need to disinfect the CF patients' nebulizer after each use. This study examined a large number of water sources (n = 7904) over a 9-year period for the presence of Pseudomonas aeruginosa. The study highlighted that jacuzzis (n = 5811; 7% positive) and hot tubs had the highest occurrence of this organism (n = 243, 21% positive). Patients with cystic fibrosis (CF) are interested in knowing what water environments are likely to be contaminated with this organism, as this bacterium is an important cause of increased morbidity and mortality in such patients. With such information, CF patients and parents may make informed decisions about lifestyle choice and water environment avoidance. © 2018 The Society for Applied Microbiology.

  14. Adult stem cell-based apexogenesis

    PubMed Central

    Li, Yao; Shu, Li-Hong; Yan, Ming; Dai, Wen-Yong; Li, Jun-Jun; Zhang, Guang-Dong; Yu, Jin-Hua

    2014-01-01

    Generally, the dental pulp needs to be removed when it is infected, and root canal therapy (RCT) is usually required in which infected dental pulp is replaced with inorganic materials (paste and gutta percha). This treatment approach ultimately brings about a dead tooth. However, pulp vitality is extremely important to the tooth itself, since it provides nutrition and acts as a biosensor to detect the potential pathogenic stimuli. Despite the reported clinical success rate, RCT-treated teeth are destined to be devitalized, brittle and susceptible to postoperative fracture. Recently, the advances and achievements in the field of stem cell biology and regenerative medicine have inspired novel biological approaches to apexogenesis in young patients suffering from pulpitis or periapical periodontitis. This review mainly focuses on the benchtop and clinical regeneration of root apex mediated by adult stem cells. Moreover, current strategies for infected pulp therapy are also discussed here. PMID:25332909

  15. A new method for using Cf-252 in SEU testing

    NASA Astrophysics Data System (ADS)

    Costantine, A.; Howard, J. W.; Becker, M.; Block, R. C.; Smith, L. S.; Soli, G. A.; Stauber, M. C.

    1990-12-01

    A system using Cf-252 and associated nuclear instrumentation has determined the single-event upset (SEU) cross section versus linear energy transfer (LET) curve for several 2K x 8 static random access memories (SRAMs). The Cf-252 fission fragments pass through a thin-film organic scintillator detector (TFD) on the way to the device under test (DUT). The TFD provides energy information for each transiting fragment. Data analysis provides the energy of the individual ion responsible for each SEU; thus, separate upset cross sections can be developed for different energy and mass regions of the californium spectrum. This californium-based device is quite small and fits onto a bench top. It provides a convenient and inexpensive supplement or alternative to accelerator and high-altitude/space SEU testing.

  16. A new method for using Cf-252 in SEU testing

    NASA Technical Reports Server (NTRS)

    Costantine, A.; Howard, J. W.; Becker, M.; Block, R. C.; Smith, L. S.; Soli, G. A.; Stauber, M. C.

    1990-01-01

    A system using Cf-252 and associated nuclear instrumentation has determined the single-event upset (SEU) cross section versus linear energy transfer (LET) curve for several 2K x 8 static random access memories (SRAMs). The Cf-252 fission fragments pass through a thin-film organic scintillator detector (TFD) on the way to the device under test (DUT). The TFD provides energy information for each transiting fragment. Data analysis provides the energy of the individual ion responsible for each SEU; thus, separate upset cross sections can be developed for different energy and mass regions of the californium spectrum. This californium-based device is quite small and fits onto a bench top. It provides a convenient and inexpensive supplement or alternative to accelerator and high-altitude/space SEU testing.

  17. Peritoneal Cell-free DNA: an innovative method for determining acute cell damage in peritoneal membrane and for monitoring the recovery process after peritonitis.

    PubMed

    Virzì, Grazia Maria; Milan Manani, Sabrina; Brocca, Alessandra; Cantaluppi, Vincenzo; de Cal, Massimo; Pastori, Silvia; Tantillo, Ilaria; Zambon, Roberto; Crepaldi, Carlo; Ronco, Claudio

    2016-02-01

    Cell-free DNA (cfDNA) is present in the peritoneal effluent of stable peritoneal dialysis (PD) patients, but there are no data on cfDNA in PD patients with peritonitis. We investigated the variation of peritoneal cfDNA levels subsequent to peritonitis in PD patients. We enrolled 53 PD patients: 30 without any history of systemic inflammation or peritonitis in the last 3 months (group A) and 23 with acute peritonitis (group B). CfDNA was quantified in the peritoneal effluent. Peritoneal samples on days 1, 3, 10, 30 and until day 120 from the start of peritonitis were collected for white blood cells (WBC) count and cfDNA evaluation in group B. Quantitative analysis of cfDNA showed significantly higher levels in group B on day 1, 3, 10 and 30 compared with group A (p < 0.05). A significant positive correlation was observed between cfDNA concentration and WBC on day 1 (rho = 0.89) and day 3 (rho = 0.5) (both, p < 0.05). However, no significant correlation was observed between cfDNA and WBC on days 10 and 30. In group B, peritoneal cfDNA levels tended to progressively decline during follow-up of peritonitis. From this decreasing curve, we estimated that 49 days are necessary to reach the value of 51 genome equivalents (GE)/ml (75th percentile in controls) and 63 days to reach 31 GE/ml (median). Our results demonstrate that cfDNA increases in peritoneal effluent of PD patients with peritonitis and tends to progressively decline in step with peritonitis resolution and membrane repair process. Peritoneal cfDNA quantification could be an innovative method to determine acute damage and an inverse index of the repair process.

  18. Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac Progenitor Cells

    PubMed Central

    Zhang, Yiqiang; Zhong, Jiang F; Qiu, Hongyu; Robb MacLellan, W.; Marbán, Eduardo; Wang, Charles

    2015-01-01

    It has been believed that mammalian adult cardiomyocytes (ACMs) are terminally-differentiated and are unable to proliferate. Recently, using a bi-transgenic ACM fate mapping mouse model and an in vitro culture system, we demonstrated that adult mouse cardiomyocytes were able to dedifferentiate into cardiac progenitor-like cells (CPCs). However, little is known about the molecular basis of their intrinsic cellular plasticity. Here we integrate single-cell transcriptome and whole-genome DNA methylation analyses to unravel the molecular mechanisms underlying the dedifferentiation and cell cycle reentry of mouse ACMs. Compared to parental cardiomyocytes, dedifferentiated mouse cardiomyocyte-derived CPCs (mCPCs) display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlated well with the methylome, our transcriptomic data showed that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation, and stemness are significantly up-regulated. In addition, implantation of mCPCs into infarcted mouse myocardium improves cardiac function with augmented left ventricular ejection fraction. Our study demonstrates that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration. PMID:26657817

  19. Ta2O5 Polycrystalline Silicon Capacitors with CF4 Plasma Treatment

    NASA Astrophysics Data System (ADS)

    Kao, Chyuan-Haur; Chen, Hsiang

    2012-04-01

    In this research, the effects of CF4 plasma treatment with post annealing on the electrical characteristics and material properties of Ta2O5 dielectrics were determined. The dielectric performance characteristics of samples under different treatment conditions were measured using equivalent oxide thickness (EOT), current density-electric field (J-E) characteristics, gate voltage shift versus time, and Weibull plots. In addition, X-ray diffraction (XRD) analysis provided insight into the changes in crystalline structure, atomic force microscopy (AFM) measurements visualized the surface roughness, and secondary ion mass spectroscopy (SIMS) revealed the distribution of fluorine ions inside the dielectric samples. Findings indicate that dielectric performance can be significantly improved by CF4 plasma treatment for 1 min with post annealing at 800 °C. The improvements in electrical characteristics were caused by the appropriate incorporation of the fluorine atoms and the removal of the dangling bonds and traps. The Ta2O5 dielectric incorporated with appropriate CF4 plasma and annealing treatments shows great promise for future generation of nonvolatile memory applications.

  20. A balance of Mad and Myc expression dictates larval cell apoptosis and adult stem cell development during Xenopus intestinal metamorphosis.

    PubMed

    Okada, Morihiro; Miller, Thomas C; Wen, Luan; Shi, Yun-Bo

    2017-05-11

    The Myc/Mad/Max network has long been shown to be an important factor in regulating cell proliferation, death and differentiation in diverse cell types. In general, Myc-Max heterodimers activate target gene expression to promote cell proliferation, although excess of c-Myc can also induce apoptosis. In contrast, Mad competes against Myc to form Mad-Max heterodimers that bind to the same target genes to repress their expression and promote differentiation. The role of the Myc/Mad/Max network during vertebrate development, especially, the so-called postembryonic development, a period around birth in mammals, is unclear. Using thyroid hormone (T3)-dependent Xenopus metamorphosis as a model, we show here that Mad1 is induced by T3 in the intestine during metamorphosis when larval epithelial cell death and adult epithelial stem cell development take place. More importantly, we demonstrate that Mad1 is expressed in the larval cells undergoing apoptosis, whereas c-Myc is expressed in the proliferating adult stem cells during intestinal metamorphosis, suggesting that Mad1 may have a role in cell death during development. By using transcription activator-like effector nuclease-mediated gene-editing technology, we have generated Mad1 knockout Xenopus animals. This has revealed that Mad1 is not essential for embryogenesis or metamorphosis. On the other hand, consistent with its spatiotemporal expression profile, Mad1 knockout leads to reduced larval epithelial apoptosis but surprisingly also results in increased adult stem cell proliferation. These findings not only reveal a novel role of Mad1 in regulating developmental cell death but also suggest that a balance of Mad and Myc controls cell fate determination during adult organ development.