An optimized swine dysentery murine model to characterize shedding and clinical disease associated with "Brachyspira hampsonii" infection.

PubMed

Ek, Courtney E; Nosach, Roman; Fernando, Champika; Huang, Yanyun; Perez, Jason Byron D S; Costa, Matheus O; Ekanayake, Samantha; Hill, Janet E; Harding, John C S

2017-08-22

The development of a mouse model as an in vivo pathogenicity screening tool for Brachyspira spp. has advanced the study of these economically important pathogens in recent years. However, none of the murine models published to date have been used to characterize the clinical signs of disease in mice, instead focusing on pathology following oral inoculation with various Brachyspira spp. The experiments described herein explore modifications of published models to characterize faecal consistency, faecal shedding and pathology in mice challenged with "Brachyspira hampsonii" clade II (Bhamp). In Experiment 1, 24 CF-1 mice were randomly allocated to one of three inoculation groups: sham (Ctrl), Bhamp, or B. hyodysenteriae (Bhyo; positive control). Half of each group was fed normal mouse chow (RMH) while the other received a low-zinc diet (TD85420). In Experiment 2, eight CF-1 mice and nine C3H/HeN mice were divided into Ctrl or Bhamp inoculation groups, and all fed TD85420. In Experiment 1, mice fed TD85420 demonstrated more severe mucoid faeces (P = 0.001; Kruskal Wallis) and faecal shedding for a significantly greater number of days (P = 0.005; Kruskal Wallis). Mean faecal scores of Bhamp inoculated mice trended higher than Ctrl (P = 0.06; Wilcoxon rank-sum) as did those of Bhyo mice (P = 0.0; Wilcoxon rank-sum). In Experiment 2, mean faecal scores of inoculated CF-1 mice were significantly greater than in C3H mice (P = 0.049; Kruskal Wallis) but no group differences in faecal shedding were observed. In both experiments, mice clustered based on the severity of colonic and caecal histopathology but high lesion scores were not always concurrent with high fecal scores. In our laboratory, CF-1 mice and the lower-zinc TD85420 diet provide a superior murine challenge model of "Brachyspira hampsonii" clade II.

Relative contribution of Prevotella intermedia and Pseudomonas aeruginosa to lung pathology in airways of patients with cystic fibrosis.

PubMed

Ulrich, Martina; Beer, Isabelle; Braitmaier, Peter; Dierkes, Michaela; Kummer, Florian; Krismer, Bernhard; Schumacher, Ulrike; Gräpler-Mainka, Ute; Riethmüller, Joachim; Jensen, Peter Ø; Bjarnsholt, Thomas; Høiby, Niels; Bellon, Gabriel; Döring, Gerd

2010-11-01

Patients with cystic fibrosis (CF) with Pseudomonas aeruginosa lung infections produce endobronchial mucus plugs allowing growth of obligate anaerobes including Prevotella spp. Whether obligate anaerobes contribute to the pathophysiology of CF lung disease is unknown. The virulence of Prevotella intermedia and Ps aeruginosa was investigated in vitro and in mice, antibodies against P intermedia in CF sera were assessed and a culture-independent detection method for P intermedia/P nigrescens in CF sputum was tested. P intermedia reached cell numbers of >10(5)->10(7) colony-forming units (CFU)/ml sputum. The majority of patients with CF (16/17; 94.1%) produced antibodies against two immunoreactive antigens of P intermedia. Culture supernatant fluids, collected from 10(9) P intermedia cells, were more cytotoxic to respiratory epithelial cells in vitro and inflammatory in mouse lungs than respective fluids from anaerobically grown Ps aeruginosa, while fluids from aerobically grown Ps aeruginosa had the highest cytotoxicity and inflammation. Both pathological effects were largely reduced when culture supernatant fluids from 10(7) cells of either species were used. P intermedia cells (∼10(6)CFU/lung) did not induce mortality in the agar beads lung infection mouse model, while Ps aeruginosa cells caused death in 30% of mice due to rapid multiplication. A P intermedia/P nigrescens-specific PNA probe was significantly more sensitive than culture-dependent diagnostic assays to detect these strict anaerobes. Ps aeruginosa and P intermedia become significantly virulent in vitro and in vivo when cell numbers exceed 10(8) CFU/lung.

A mouse model for the cystic fibrosis delta F508 mutation.

PubMed Central

van Doorninck, J H; French, P J; Verbeek, E; Peters, R H; Morreau, H; Bijman, J; Scholte, B J

1995-01-01

Most cystic fibrosis (CF) patients produce a mutant form (delta F508) of the cystic fibrosis transmembrane conductance regulator (CFTR), which is not properly processed in normal cells but is active as a chloride channel in several experimental systems. We used a double homologous recombination ('Hit and Run') procedure to generate a mouse model for the delta F508 mutation. Targeted embryonic stem (ES) cells (Hit clones) were found; of these either 80 or 20% of the clones had lost the delta F508 mutation, depending on the distance between the linearization site in the targeting construct and the delta F508 mutation. Correctly targeted clones underwent a second selection step resulting in ES cell clones (Run clones) heterozygous for the delta F508 mutation with an efficiency of 2-7%. Chimeric mice were generated and offspring homozygous for the delta F508 mutation showed electrophysiological abnormalities in nasal epithelium, gallbladder and in the intestine, and histological abnormalities in the intestine, typical of CF. Our data suggest that the delta F508 mice have residual delta F508 CFTR activity which would explain the mild pathology of the delta F508 mice. The delta F508 mouse may provide a useful model for the study of the processing defect of delta F508 CFTR and for the development of novel therapeutic approaches based on circumvention of the processing block. Images PMID:7556083

FOXO1 content is reduced in cystic fibrosis and increases with IGF-I treatment.

PubMed

Smerieri, Arianna; Montanini, Luisa; Maiuri, Luigi; Bernasconi, Sergio; Street, Maria E

2014-10-08

Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fibrosis (CF). The mechanisms underlying this condition are not well understood, and a possible role of insulin resistance is debated. We investigated insulin signal transduction in CF. Total insulin receptor, IRS1, p85 PI3K, and AKT contents were substantially normal in CF cells (CFBE41o-), whereas winged helix forkhead (FOX)O1 contents were reduced both in baseline conditions and after insulin stimulation. In addition, CF cells showed increased ERK1/2, and reduced β2 arrestin contents. No significant change in SOCS2 was observed. By using a CFTR inhibitor and siRNA, changes in FOXO1 were related to CFTR loss of function. In a CF-affected mouse model, FOXO1 content was reduced in the muscle while no significant difference was observed in liver and adipose tissue compared with wild-type. Insulin-like growth factor 1 (IGF-I) increased FOXO1 content in vitro and in vivo in muscle and adipose tissue. In conclusion; we present the first description of reduced FOXO1 content in CF, which is compatible with reduced gluconeogenesis and increased adipogenesis, both features of insulin insensitivity. IGF-I treatment was effective in increasing FOXO1, thereby suggesting that it could be considered as a potential treatment in CF patients possibly to prevent and treat cystic fibrosis-related diabetes.

Comparative biology of rAAV transduction in ferret, pig and human airway epithelia.

PubMed

Liu, X; Luo, M; Guo, C; Yan, Z; Wang, Y; Engelhardt, J F

2007-11-01

Differences between rodent and human airway cell biology have made it difficult to translate recombinant adeno-associated virus (rAAV)-mediated gene therapies to the lung for cystic fibrosis (CF). As new ferret and pig models for CF become available, knowledge about host cell/vector interactions in these species will become increasingly important for testing potential gene therapies. To this end, we have compared the transduction biology of three rAAV serotypes (AAV1, 2 and 5) in human, ferret, pig and mouse-polarized airway epithelia. Our results indicate that apical transduction of ferret and pig airway epithelia with these rAAV serotypes closely mirrors that observed in human epithelia (rAAV1>rAAV2 congruent withrAAV5), while transduction of mouse epithelia was significantly different (rAAV1>rAAV5>rAAV2). Similarly, ferret, pig and human epithelia also shared serotype-specific differences in the polarity (apical vs basolateral) and proteasome dependence of rAAV transduction. Despite these parallels, N-linked sialic acid receptors were required for rAAV1 and rAAV5 transduction of human and mouse airway epithelia, but not ferret or pig airway epithelia. Hence, although the airway tropisms of rAAV serotypes 1, 2 and 5 are conserved better among ferret, pig and human as compared to mouse, viral receptors/co-receptors appear to maintain considerable species diversity.

Lung pathology in response to repeated exposure to Staphylococcus aureus in congenic residual function cystic fibrosis mice does not increase in response to decreased CFTR levels or increased bacterial load.

PubMed

Davidson, Donald J; Webb, Sheila; Teague, Peter; Govan, John R W; Dorin, Julia R

2004-01-01

To establish the role of defects in murine Cftr in the susceptibility to Staphylococcus aureus lung disease using mouse models of cystic fibrosis (CF), congenic or inbred strains. We describe the histopathological analyses of CF mice repeatedly exposed by aerosolisation to a CF isolate of S. aureus, using residual function Cftr mice and compound heterozygotes generated by intercrossing these with Cftr 'null' mice, all congenic on the C57Bl6/N background. We demonstrate that mice congenic on the C57Bl/6 background develop significantly more severe lung pathology than non-CF littermates in response to repeated exposure to the most frequent early CF lung pathogen S. aureus. Furthermore, reducing the level of Cftr by half in compound heterozygote mice does not impact upon disease severity, even in response to an increased bacterial dose. These results are consistent with an airway clearance defect, or abnormal inflammatory response secondary to Cftr mutation. These studies confirm the primary role for Cftr mutation in the development of this lung phenotype. In addition, these results demonstrate that a further 50% decrease in residual wild-type Cftr mRNA levels in this model does not impact the severity of the histopathological response to S. aureus, suggesting a critical threshold level for functional CFTR. Copyright 2004 S. Karger AG, Basel

Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype.

PubMed

De Lisle, Robert C; Mueller, Racquel; Roach, Eileen

2010-09-15

Cystic fibrosis (CF) is caused by mutations in the CFTR gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl- channel, would improve the intestinal phenotype in CF mice. Cftr(tm1UNC) (CF) and wildtype (WT) littermate mice on the C57BL/6J background were used. Lubiprostone (10 μg/kg-day) was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16S gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR. Crypt width in control CF mice was 700% that of WT mice (P < 0.001). Lubiprostone did not affect WT crypt width but, unexpectedly, increased CF crypt width 22% (P = 0.001). Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (P = 0.008). Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (P = 0.005). Lubiprostone increased gastric emptying at 20 min postgavage in both WT (P < 0.001) and CF mice (P < 0.001). Lubiprostone enhanced small intestinal transit in WT mice (P = 0.024) but not in CF mice (P = 0.377). Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels. These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice suggests the possibility that lubiprostone increases mucus secretion.

Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype

PubMed Central

2010-01-01

Background Cystic fibrosis (CF) is caused by mutations in the CFTR gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl- channel, would improve the intestinal phenotype in CF mice. Methods Cftrtm1UNC (CF) and wildtype (WT) littermate mice on the C57BL/6J background were used. Lubiprostone (10 μg/kg-day) was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16S gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR. Results Crypt width in control CF mice was 700% that of WT mice (P < 0.001). Lubiprostone did not affect WT crypt width but, unexpectedly, increased CF crypt width 22% (P = 0.001). Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (P = 0.008). Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (P = 0.005). Lubiprostone increased gastric emptying at 20 min postgavage in both WT (P < 0.001) and CF mice (P < 0.001). Lubiprostone enhanced small intestinal transit in WT mice (P = 0.024) but not in CF mice (P = 0.377). Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels. Conclusions These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice suggests the possibility that lubiprostone increases mucus secretion. PMID:20843337

Activation of intestinal Cl- secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator.

PubMed

Bijvelds, Marcel J C; Bot, Alice G M; Escher, Johanna C; De Jonge, Hugo R

2009-09-01

Lubiprostone alleviates constipation by stimulating intestinal fluid secretion, purportedly through activation of ClC-2-type Cl(-) channels. Intestinal obstruction is also a recurrent cause of distress in cystic fibrosis (CF) patients, caused by loss of CF transmembrane conductance regulator (CFTR) Cl(-) channel activity. Because ClC-2 recruitment might be beneficial to CF patients, we investigated lubiprostone's mode of action. Cl(-) transport was measured in an Ussing chamber, in 3 model systems: (1) T84 colonocytes, (2) intestinal epithelium of wild-type and CF mice, and (3) intestinal epithelium of CF patients and controls. In T84 monolayers, lubiprostone induced a robust secretory response. Selective permeabilization of the basolateral plasma membrane revealed that lubiprostone activated an apical Cl(-) conductance. The lubiprostone response was attenuated by H89, an inhibitor of the cAMP-dependent protein kinase, and lubiprostone precluded responsiveness to the cAMP agonist forskolin. CFTR blockage by CFTRinh172, but not ClC-2 blockage by CdCl(2), inhibited the lubiprostone response. Lubiprostone induced a CdCl(2)-insensitive secretory response in mouse intestine, but failed to induce intestinal Cl(-) secretion in Cftr-null mice. Correspondingly, lubiprostone induced a secretory response in human intestinal epithelium, but not in tissue of CF patients. The EP(4)-type prostanoid receptor antagonist L-161,982 blocked the lubiprostone response in all 3 models studied. In T84 cells, lubiprostone induced a rise in cAMP levels that was sensitive to EP(4)-receptor blockage. Lubiprostone enhances intestinal Cl(-) and fluid secretion via prostanoid receptor signaling, triggering activation of CFTR. Therefore, it is of limited use for treatment of CF-related intestinal disease.

Pulmonary Emphysema in Cystic Fibrosis Detected by Densitometry on Chest Multidetector Computed Tomography

PubMed Central

Wielpütz, Mark O.; Weinheimer, Oliver; Eichinger, Monika; Wiebel, Matthias; Biederer, Jürgen; Kauczor, Hans-Ulrich; Heußel, Claus P.

2013-01-01

Background Histopathological studies on lung specimens from patients with cystic fibrosis (CF) and recent results from a mouse model indicate that emphysema may contribute to CF lung disease. However, little is known about the relevance of emphysema in patients with CF. In the present study, we used computationally generated density masks based on multidetector computed tomography (MDCT) of the chest for non-invasive characterization and quantification of emphysema in CF. Methods Volumetric MDCT scans were acquired in parallel to pulmonary function testing in 41 patients with CF (median age 20.1 years; range 7-66 years) and 21 non-CF controls (median age 30.4 years; range 4-68 years), and subjected to dedicated software. The lung was segmented, low attenuation volumes below a threshold of -950 Hounsfield units were assigned to emphysema volume (EV), and the emphysema index was computed (EI). Results were correlated with forced expiratory volume in 1 s percent predicted (FEV1%), residual volume (RV), and RV/total lung capacity (RV/TLC). Results We show that EV was increased in CF (457±530 ml) compared to non-CF controls (78±90 ml) (P<0.01). EI was also increased in CF (7.7±7.5%) compared to the control group (1.2±1.4%) (P<0.05). EI correlated inversely with FEV1% (rs=-0.66), and directly with RV (rs=0.69) and RV/TLC (rs=0.47) in patients with CF (P<0.007), but not in non-CF controls. Emphysema in CF was detected from early adolescence (~13 years) and increased with age (rs=0.67, P<0.001). Conclusions Our results indicate that early onset emphysema detected by densitometry on chest MDCT is a characteristic pathology that contributes to airflow limitation and may serve as a novel endpoint for monitoring lung disease in CF. PMID:23991177

Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice.

PubMed

Crosby, Jeff R; Zhao, Chenguang; Jiang, Chong; Bai, Dong; Katz, Melanie; Greenlee, Sarah; Kawabe, Hiroshi; McCaleb, Michael; Rotin, Daniela; Guo, Shuling; Monia, Brett P

2017-11-01

Epithelial sodium channel (ENaC, Scnn1) hyperactivity in the lung leads to airway surface dehydration and mucus accumulation in cystic fibrosis (CF) patients and in mice with CF-like lung disease. We identified several potent ENaC specific antisense oligonucleotides (ASOs) and tested them by inhalation in mouse models of CF-like lung disease. The inhaled ASOs distributed into lung airway epithelial cells and decreased ENaC expression by inducing RNase H1-dependent degradation of the targeted Scnn1a mRNA. Aerosol delivered ENaC ASO down-regulated mucus marker expression and ameliorated goblet cell metaplasia, inflammation, and airway hyper-responsiveness. Lack of systemic activity of ASOs delivered via the aerosol route ensures the safety of this approach. Our results demonstrate that antisense inhibition of ENaC in airway epithelial cells could be an effective and safe approach for the prevention and reversal of lung symptoms in CF and potentially other inflammatory diseases of the lung. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Celecoxib restores angiogenic factor expression at the maternal-fetal interface in the BPH/5 mouse model of preeclampsia.

PubMed

Reijnders, Dorien; Liu, Chin-Chi; Xu, Xinjing; Zhao, Anna M; Olson, Kelsey N; Butler, Scott D; Douglas, Nataki C; Sones, Jenny L

2018-05-01

Preeclampsia (PE), a hypertensive disease of pregnancy, is a leading cause of fetal and maternal morbidity/mortality. Early angiogenic and inflammatory disturbances within the placenta are thought to underlie the development of the maternal PE syndrome and poor pregnancy outcomes. However, the exact etiology remains largely unknown. Here, we use the BPH/5 mouse model of PE to elucidate the way in which inflammation early in pregnancy contributes to abnormal expression of angiogenic factors at the maternal-fetal interface. We have previously described improvement in maternal hypertension and fetal growth restriction in this model after treatment with the anti-inflammatory cyclooxygenase-2 (Cox2) specific inhibitor celecoxib. To further characterize the mechanisms by which celecoxib improves poor pregnancy outcomes in BPH/5 mice, we determined expression of angiogenic factors and complement pathway components after celecoxib. In BPH/5 implantation sites there was increased hypoxia inducible factor-1α ( Hif1α), heme oxygenase-1 ( Ho-1), and stem cell factor ( Scf) mRNA concomitant with elevated prostaglandin synthase 2 ( Ptgs2), encoding Cox2, and elevated VEGF protein. Angiopoietin 1 ( Ang1), tunica interna endothelial cell kinase-2 receptor ( Tie2), complement factor 3 ( C3), and complement factor B ( CfB) were increased in midgestation BPH/5 placentae. Whereas BPH/5 expression levels of VEGF, Ang1, and Tie2 normalized after celecoxib, placental C3 and CfB mRNA remained unchanged. However, celecoxib did reduce the pregnancy-specific circulating soluble fms-like tyrosine kinase-1 (sFlt-1) rise in BPH/5 mice at midgestation. These data show that elevated Cox2 during implantation contributes to placental angiogenic factor imbalances in the BPH/5 mouse model of PE.

Non-invasive airway health measurement using synchrotron x-ray microscopy of high refractive index glass microbeads

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

Donnelley, Martin, E-mail: martin.donnelley@adelaide.edu.au; Farrow, Nigel; Parsons, David

Cystic fibrosis (CF) is caused by a gene defect that compromises the ability of the mucociliary transit (MCT) system to clear the airways of debris and pathogens. To directly characterise airway health and the effects of treatments we have developed a synchrotron X-ray microscopy method that non-invasively measures the local rate and patterns of MCT behaviour. Although the nasal airways of CF mice exhibit the CF pathophysiology, there is evidence that nasal MCT is not altered in CF mice1. The aim of this experiment was to determine if our non-invasive local airway health assessment method could identify differences in nasalmore » MCT rate between normal and CF mice, information that is potentially lost in bulk MCT measurements. Experiments were performed on the BL20XU beamline at the SPring-8 Synchrotron in Japan. Mice were anaesthetized, a small quantity of micron-sized marker particles were delivered to the nose, and images of the nasal airways were acquired for 15 minutes. The nasal airways were treated with hypertonic saline or mannitol to increase surface hydration and MCT. Custom software was used to locate and track particles and calculate individual and bulk MCT rates. No statistically significant differences in MCT rate were found between normal and CF mouse nasal airways or between treatments. However, we hope that the improved sensitivity provided by this technique will accelerate the ability to identify useful CF lung disease-modifying interventions in small animal models, and enhance the development and efficacy of proposed new therapies.« less

Non-invasive airway health measurement using synchrotron x-ray microscopy of high refractive index glass microbeads

NASA Astrophysics Data System (ADS)

Donnelley, Martin; Morgan, Kaye; Farrow, Nigel; Siu, Karen; Parsons, David

2016-01-01

Cystic fibrosis (CF) is caused by a gene defect that compromises the ability of the mucociliary transit (MCT) system to clear the airways of debris and pathogens. To directly characterise airway health and the effects of treatments we have developed a synchrotron X-ray microscopy method that non-invasively measures the local rate and patterns of MCT behaviour. Although the nasal airways of CF mice exhibit the CF pathophysiology, there is evidence that nasal MCT is not altered in CF mice1. The aim of this experiment was to determine if our non-invasive local airway health assessment method could identify differences in nasal MCT rate between normal and CF mice, information that is potentially lost in bulk MCT measurements. Experiments were performed on the BL20XU beamline at the SPring-8 Synchrotron in Japan. Mice were anaesthetized, a small quantity of micron-sized marker particles were delivered to the nose, and images of the nasal airways were acquired for 15 minutes. The nasal airways were treated with hypertonic saline or mannitol to increase surface hydration and MCT. Custom software was used to locate and track particles and calculate individual and bulk MCT rates. No statistically significant differences in MCT rate were found between normal and CF mouse nasal airways or between treatments. However, we hope that the improved sensitivity provided by this technique will accelerate the ability to identify useful CF lung disease-modifying interventions in small animal models, and enhance the development and efficacy of proposed new therapies.

Antidepressant-like effect of m-trifluoromethyl-diphenyl diselenide in the mouse forced swimming test involves opioid and serotonergic systems.

PubMed

Brüning, César Augusto; Souza, Ana Cristina Guerra; Gai, Bibiana Mozzaquatro; Zeni, Gilson; Nogueira, Cristina Wayne

2011-05-11

Serotonergic and opioid systems have been implicated in major depression and in the action mechanism of antidepressants. The organoselenium compound m-trifluoromethyl-diphenyl diselenide (m-CF(3)-PhSe)(2) shows antioxidant and anxiolytic activities and is a selective inhibitor of monoamine oxidase A activity. The present study was designed to investigate the antidepressant-like effect of (m-CF(3)-PhSe)(2) in female mice, employing the forced swimming test. The involvement of the serotonergic and opioid systems in the antidepressant-like effect of (m-CF(3)-PhSe)(2) was appraised. (m-CF(3)-PhSe)(2) at doses of 50 and 100mg/kg (p.o.) exhibited antidepressant-like action in the forced swimming test. The effect of (m-CF(3)-PhSe)(2) (50mg/kg p.o.) was prevented by pretreatment of mice with WAY100635 (0.1mg/kg, s.c. a selective 5-HT(1A) receptor antagonist), ritanserin (4 mg/kg, i.p., a non-selective 5HT(2A/2C) receptor antagonist), ondansetron (1mg/kg, i.p., a selective 5-HT(3) receptor antagonist) and naloxone (1mg/kg, i.p., a non-selective antagonist of opioid receptors). These results suggest that (m-CF(3)-PhSe)(2) produced an antidepressant-like effect in the mouse forced swimming test and this effect seems most likely to be mediated through an interaction with serotonergic and opioid systems. Copyright © 2011 Elsevier B.V. All rights reserved.

Mucus secretion by single tracheal submucosal glands from normal and cystic fibrosis transmembrane conductance regulator knockout mice

PubMed Central

Ianowski, Juan P; Choi, Jae Young; Wine, Jeffrey J; Hanrahan, John W

2007-01-01

Submucosal glands line the cartilaginous airways and produce most of the antimicrobial mucus that keeps the airways sterile. The glands are defective in cystic fibrosis (CF), but how this impacts airway health remains uncertain. Although most CF mouse strains exhibit mild airway defects, those with the C57Bl/6 genetic background have increased airway pathology and susceptibility to Pseudomonas. Thus, they offer the possibility of studying whether, and if so how, abnormal submucosal gland function contributes to CF airway disease. We used optical methods to study fluid secretion by individual glands in tracheas from normal, wild-type (WT) mice and from cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice (Cftrm1UNC/Cftrm1UNC; CF mice). Glands from WT mice qualitatively resembled those in humans by responding to carbachol and vasoactive intestinal peptide (VIP), although the relative rates of VIP- and forskolin-stimulated secretion were much lower in mice than in large mammals. The pharmacology of mouse gland secretion was also similar to that in humans; adding bumetanide or replacement of HCO3− by Hepes reduced the carbachol response by ∼50%, and this inhibition increased to 80% when both manoeuvres were performed simultaneously. It is important to note that glands from CFTR knockout mice responded to carbachol but did not secrete when exposed to VIP or forskolin, as has been shown previously for glands from CF patients. Tracheal glands from WT and CF mice both had robust secretory responses to electrical field stimulation that were blocked by tetrodotoxin. It is interesting that local irritation of the mucosa using chili pepper oil elicited secretion from WT glands but did not stimulate glands from CF mice. These results clarify the mechanisms of murine submucosal gland secretion and reveal a novel defect in local regulation of glands lacking CFTR which may also compromise airway defence in CF patients. PMID:17204498

Effective silencing of ENaC by siRNA delivered with epithelial-targeted nanocomplexes in human cystic fibrosis cells and in mouse lung.

PubMed

Tagalakis, Aristides D; Munye, Mustafa M; Ivanova, Rositsa; Chen, Hanpeng; Smith, Claire M; Aldossary, Ahmad M; Rosa, Luca Z; Moulding, Dale; Barnes, Josephine L; Kafetzis, Konstantinos N; Jones, Stuart A; Baines, Deborah L; Moss, Guy W J; O'Callaghan, Christopher; McAnulty, Robin J; Hart, Stephen L

2018-05-10

Loss of the cystic fibrosis transmembrane conductance regulator in cystic fibrosis (CF) leads to hyperabsorption of sodium and fluid from the airway due to upregulation of the epithelial sodium channel (ENaC). Thickened mucus and depleted airway surface liquid (ASL) then lead to impaired mucociliary clearance. ENaC regulation is thus a promising target for CF therapy. Our aim was to develop siRNA nanocomplexes that mediate effective silencing of airway epithelial ENaC in vitro and in vivo with functional correction of epithelial ion and fluid transport. We investigated translocation of nanocomplexes through mucus and their transfection efficiency in primary CF epithelial cells grown at air-liquid interface (ALI).Short interfering RNA (SiRNA)-mediated silencing was examined by quantitative RT-PCR and western analysis of ENaC. Transepithelial potential (V t ), short circuit current (I sc ), ASL depth and ciliary beat frequency (CBF) were measured for functional analysis. Inflammation was analysed by histological analysis of normal mouse lung tissue sections. Nanocomplexes translocated more rapidly than siRNA alone through mucus. Transfections of primary CF epithelial cells with nanocomplexes targeting αENaC siRNA, reduced αENaC and βENaC mRNA by 30%. Transfections reduced V t , the amiloride-sensitive I sc and mucus protein concentration while increasing ASL depth and CBF to normal levels. A single dose of siRNA in mouse lung silenced ENaC by approximately 30%, which persisted for at least 7 days. Three doses of siRNA increased silencing to approximately 50%. Nanoparticle-mediated delivery of ENaCsiRNA to ALI cultures corrected aspects of the mucociliary defect in human CF cells and offers effective delivery and silencing in vivo. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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.

Increased capillary permeability mediated by a dengue virus-induced lymphokine.

PubMed Central

Khanna, M; Chaturvedi, U C; Sharma, M C; Pandey, V C; Mathur, A

1990-01-01

The mechanism of increased capillary permeability, seen in cases of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), is not known. Dengue type 2 virus (DV) is known to induce production of a lymphokine, the cytotoxic factor (CF), by the T lymphocytes of mouse spleen. The data presented here show that intraperitoneal inoculation of CF in mice results in increased capillary permeability in a dose-dependent manner, as shown by leakage of intravenously injected radiolabelled iodine (125I) or Evans blue dye. Peak leakage occurred 30 min after inoculation of CF and the vascular integrity was restored by 2 hr. The increase in capillary permeability was abrogated by pretreatment of mice with anti-CF antibodies, avil (H1 receptor blocker) or ranitidine (H2 receptor blocker). The findings thus show that a DV-induced lymphokine, the CF, increases the capillary permeability via release of histamine. PMID:2312168

The Nox1/4 dual inhibitor GKT137831 or Nox4 knockdown inhibits Angiotensin-II-induced adult mouse cardiac fibroblast proliferation and migration. AT1 physically associates with Nox4

PubMed Central

Somanna, Naveen K.; Valente, Anthony J.; Krenz, Maike; Fay, William P.; Delafontaine, Patrice; Chandrasekar, Bysani

2017-01-01

Both oxidative stress and inflammation contribute to chronic hypertension-induced myocardial fibrosis and adverse cardiac remodeling. Here we investigated whether angiotensin (Ang)-II-induced fibroblast proliferation and migration are NADPH oxidase (Nox) 4/ROS and IL-18 dependent. Our results show that the potent induction of mouse cardiac fibroblast (CF) proliferation and migration by Ang-II is markedly attenuated by Nox4 knockdown and the Nox inhibitor DPI. Further, Nox4 knockdown and DPI pre-treatment attenuate Ang-II-induced IL-18, IL-18Rα and collagen expression, and MMP9 activation. While neutralization of IL-18 blunted Ang-II-induced CF proliferation and migration, knockdown of MMP9 attenuated CF migration. The antioxidant NAC and the cell-permeable SOD mimetics Tempol, MnTBAP, and MnTMPyP attenuated oxidative stress and inhibit CF proliferation and migration. The Nox1/Nox4 dual inhibitor GKT137831 also blunted Ang-II-induced H2O2 production and CF proliferation and migration. Further, AT1 binds Nox4, and Ang-II enhanced their physical association. Notably, GKT137831 attnuated the AT1/Nox4 interaction. These results indicate that Ang-II induces CF proliferation and migration in part via Nox4/ROS-dependent IL-18 induction and MMP9 activation, and may involve AT1/Nox4 physical association. Thus, either (i) neutralizing IL-18, (ii) blocking AT1/Nox4 interaction or (iii) use of the Nox1/Nox4 inhibitor GKT137831 may have therapeutic potential in chronic hypertension-induced adverse cardiac remodeling. PMID:26445208

Quantitative and semi-quantitative immunoassay of growth factors and cytokines in the conditioned medium of STO and CF-1 mouse feeder cells

USDA-ARS?s Scientific Manuscript database

Feeder-cells of irradiated mouse fibroblasts are commonly used for, and are generally necessary for, the in vitro maintenance and growth of many fastidious cell types, particularly embryonic stem cells or induced pluripotent stem cells. Quantitative and semi-quantitative immunoassays were performed...

Renal proximal tubule function is preserved in Cftrtm2camΔF508 cystic fibrosis mice

PubMed Central

Kibble, J D; Balloch, K J D; Neal, A M; Hill, C; White, S; Robson, L; Green, R; Taylor, C J

2001-01-01

Changes in proximal tubule function have been reported in cystic fibrosis patients. The aim of this study was to investigate proximal tubule function in the Cftrtm2camΔF508 cystic fibrosis (CF) mouse model. A range of techniques were used including renal clearance studies, in situ microperfusion, RT-PCR and whole-cell patch clamping. Renal Na+ clearance was similar in wild-type (1.4 ± 0.3 μl min−1, number of animals, N= 12) and CF mice (1.6 ± 0.4 μl min−1, N= 7) under control conditions. Acute extracellular volume expansion resulted in significant natriuresis in wild-type (7.0 ± 0.8 μl min−1, N= 8) and CF mice (9.3 ± 1.4 μl min−1, N= 9); no difference between genotypes was observed. In situ microperfusion revealed that fluid absorptive rate (Jv) was similar under control conditions between wild-type (2.2 ± 0.4 nl mm−1 min−1, n= 10) and CF mice (1.9 ± 0.3 nl mm−1 min−1, n= 11). Addition of a forskolin-dibutyryl cAMP (db-cAMP) cocktail to the perfusate caused no significant change in Jv in either wild-type (2.6 ± 0.7 nl mm−1 min−1, n= 10) or Cftrtm2camΔF508 mice (2.0 ± 0.5 nl mm−1 min−1, n= 10). CFTR expression was confirmed in samples of outer cortex using RT-PCR. However, no evidence for functional CFTR was obtained when outer cortical cells were stimulated with protein kinase A or forskolin-db-cAMP using whole-cell patch clamping. In conclusion, no functional deficit in proximal tubule function was found in Cftrtm2camΔF508 mice. This may be a consequence of a lack of whole-cell cAMP-dependent Cl− conductance in mouse proximal tubule cells. PMID:11306663

A novel surgical approach for intratracheal administration of bioactive agents in a fetal mouse model.

PubMed

Carlon, Marianne S; Toelen, Jaan; da Cunha, Marina Mori; Vidović, Dragana; Van der Perren, Anke; Mayer, Steffi; Sbragia, Lourenço; Nuyts, Johan; Himmelreich, Uwe; Debyser, Zeger; Deprest, Jan

2012-10-31

Prenatal pulmonary delivery of cells, genes or pharmacologic agents could provide the basis for new therapeutic strategies for a variety of genetic and acquired diseases. Apart from congenital or inherited abnormalities with the requirement for long-term expression of the delivered gene, several non-inherited perinatal conditions, where short-term gene expression or pharmacological intervention is sufficient to achieve therapeutic effects, are considered as potential future indications for this kind of approach. Candidate diseases for the application of short-term prenatal therapy could be the transient neonatal deficiency of surfactant protein B causing neonatal respiratory distress syndrome(1,2) or hyperoxic injuries of the neonatal lung(3). Candidate diseases for permanent therapeutic correction are Cystic Fibrosis (CF)(4), genetic variants of surfactant deficiencies(5) and α1-antitrypsin deficiency(6). Generally, an important advantage of prenatal gene therapy is the ability to start therapeutic intervention early in development, at or even prior to clinical manifestations in the patient, thus preventing irreparable damage to the individual. In addition, fetal organs have an increased cell proliferation rate as compared to adult organs, which could allow a more efficient gene or stem cell transfer into the fetus. Furthermore, in utero gene delivery is performed when the individual's immune system is not completely mature. Therefore, transplantation of heterologous cells or supplementation of a non-functional or absent protein with a correct version should not cause immune sensitization to the cell, vector or transgene product, which has recently been proven to be the case with both cellular and genetic therapies(7). In the present study, we investigated the potential to directly target the fetal trachea in a mouse model. This procedure is in use in larger animal models such as rabbits and sheep(8), and even in a clinical setting(9), but has to date not been performed before in a mouse model. When studying the potential of fetal gene therapy for genetic diseases such as CF, the mouse model is very useful as a first proof-of-concept because of the wide availability of different transgenic mouse strains, the well documented embryogenesis and fetal development, less stringent ethical regulations, short gestation and the large litter size. Different access routes have been described to target the fetal rodent lung, including intra-amniotic injection(10-12), (ultrasound-guided) intrapulmonary injection(13,14) and intravenous administration into the yolk sac vessels(15,16) or umbilical vein(17). Our novel surgical procedure enables researchers to inject the agent of choice directly into the fetal mouse trachea which allows for a more efficient delivery to the airways than existing techniques(18).

Anticonvulsant effects of a triheptanoin diet in two mouse chronic seizure models

PubMed Central

Willis, Sarah; Stoll, James; Sweetman, Lawrence; Borges, Karin

2010-01-01

We hypothesized that in epileptic brains citric acid cycle intermediate levels may be deficient leading to hyperexcitability. Anaplerosis is the metabolic refilling of deficient metabolites. Our goal was to determine the anticonvulsant effects of feeding triheptanoin, the triglyceride of anaplerotic heptanoate. CF1 mice were fed 0-35% calories from triheptanoin. Body weights and dietary intake were similar in mice fed triheptanoin vs. standard diet. Triheptanoin feeding increased blood propionyl-carnitine levels, signifying its metabolism. 35%, but not 20%, triheptanoin delayed development of corneal kindled seizures. After pilocarpine-induced status epilepticus (SE), triheptanoin feeding increased the pentylenetetrazole tonic seizure threshold during the chronically epileptic stage. Mice in the chronically epileptic stage showed various changes in brain metabolite levels, including a reduction in malate. Triheptanoin feeding largely restored a reduction in propionyl-CoA levels and increased methylmalonyl-CoA levels in SE mice. In summary, triheptanoin was anticonvulsant in two chronic mouse models and increased levels of anaplerotic precursor metabolites in epileptic mouse brains. The mechanisms of triheptanoin's effects and its efficacy in humans suffering from epilepsy remain to be determined. PMID:20691264

Dynamic changes in leptin distribution in the progression from ovum to blastocyst of the pre-implantation mouse embryo

PubMed Central

Schulz, Laura C.; Roberts, R. Michael

2011-01-01

The hormone leptin, which is primarily produced by adipose tissue, is a critical permissive factor for multiple reproductive events in the mouse, including implantation. In the CD1 strain, maternally-derived leptin from the oocyte becomes differentially distributed among blastomeres of pre-implantation embryos to create a polarized pattern, a feature consistent with a model of development in which blastomeres are biased towards a particular fate as early as the 2-cell stage. Here, we have confirmed that embryonic leptin is of maternal origin and re-examined leptin distribution in two distinct strains in which embryos were derived after either normal ovulation or superovulation. A polarized pattern of leptin distribution was found in the majority of both CD1 and CF1 embryos (79.1 % and 76.9 %, respectively) collected following superovulation, but was reduced, particularly in CF1 embryos (29.8 %; p < 0.0001), after natural ovulation. The difference in leptin asymmetries in the CF1 strain arose between ovulation and the first cleavage division, and was not affected by removal of the zona pellucida. Presence or absence of leptin polarization was not linked to differences in ability of embryos to develop normally to blastocyst. In the early blastocyst, leptin was confined subcortically to trophectoderm but upon blastocoel expansion it was lost from cells. Throughout development leptin co-localized with LRP2, a multi-ligand transport protein, and its patterning resembled that noted for the maternal-effect proteins OOEP, NLRP5, and PADI6, suggesting that it is a component of the subcortical maternal complex with as yet unknown significance in pre-implantation development. PMID:21444625

m-Trifluoromethyl-diphenyl diselenide, a multi-target selenium compound, prevented mechanical allodynia and depressive-like behavior in a mouse comorbid pain and depression model.

PubMed

Brüning, César Augusto; Martini, Franciele; Soares, Suelen Mendonça; Sampaio, Tuane Bazanella; Gai, Bibiana Mozzaquatro; Duarte, Marta M M F; Nogueira, Cristina Wayne

2015-12-03

Chronic pain and depression are two complex states that often coexist in the clinical setting and traditional antidepressants and analgesics have shown limited clinical efficacy. There is an intricate communication between the immune system and the central nervous system and inflammation has been considered a common mediator of pain-depression comorbidity. This study evaluated the effect of m-trifluoromethyl diphenyl diselenide [(m-CF3-PhSe)2], an organoselenium compound that has been reported to have both antinociceptive and antidepressant-like actions, in the comorbidity of chronic pain and depression induced by partial sciatic nerve ligation (PSNL) in an inflammatory approach. Mice were submitted to PSNL during 4weeks and treated with (m-CF3-PhSe)2 acutely (0.1-10mg/kg, i.g.) or subchronically (0.1mg/kg, i.g., once a day during the 3rd and 4th weeks). Both treatments prevented PSNL-increased pain sensitivity and depressive-like behavior observed in Von-Frey hair (VFH) and forced swimming (FST) tests, respectively. These effects could be mainly associated with an anti-inflammatory action of (m-CF3-PhSe)2 which reduced the levels of pro-inflammatory cytokines, NF-κB and COX-2, and p38 MAPK activation that were increased by PSNL. (m-CF3-PhSe)2 also increased the BDNF levels and reduced glutamate release and 5-HT uptake altered by PSNL. Although acute and subchronic treatments with (m-CF3-PhSe)2 prevented these alterations induced by PSNL, the best results were found when (m-CF3-PhSe)2 was subchronically administered to mice. Considering the potential common mechanisms involved in the comorbidity of inflammation-induced depression and chronic pain, the results found in this study indicate that (m-CF3-PhSe)2 could become an interesting molecule to treat long-lasting pathological pain associated with depression. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Comparative processing and function of human and ferret cystic fibrosis transmembrane conductance regulator.

PubMed

Fisher, John T; Liu, Xiaoming; Yan, Ziying; Luo, Meihui; Zhang, Yulong; Zhou, Weihong; Lee, Ben J; Song, Yi; Guo, Chenhong; Wang, Yujiong; Lukacs, Gergely L; Engelhardt, John F

2012-06-22

The most common cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation is ΔF508, and this causes cystic fibrosis (CF). New CF models in the pig and ferret have been generated that develop lung, pancreatic, liver, and intestinal pathologies that reflect disease in CF patients. Species-specific biology in the processing of CFTR has demonstrated that pig and mouse ΔF508-CFTR proteins are more effectively processed to the apical membrane of airway epithelia than human ΔF508-CFTR. The processing behavior of ferret WT- and ΔF508-CFTR proteins remains unknown, and such information is important to predicting the utility of a ΔF508-CFTR ferret. To this end, we sought to compare processing, membrane stability, and function of human and ferret WT- and ΔF508-CFTR proteins in a heterologous expression system using HT1080, HEK293T, BHK21, and Cos7 cells as well as human and ferret CF polarized airway epithelia. Analysis of the protein processing and stability by metabolic pulse-chase and surface On-Cell Western blots revealed that WT-fCFTR half-life and membrane stability were increased relative to WT-hCFTR. Furthermore, in BHK21, Cos7, and CuFi cells, human and ferret ΔF508-CFTR processing was negligible, whereas low levels of processing of ΔF508-fCFTR could be seen in HT1080 and HEK293T cells. Only the WT-fCFTR, but not ΔF508-fCFTR, produced functional cAMP-inducible chloride currents in both CF human and ferret airway epithelia. Further elucidation of the mechanism responsible for elevated fCFTR protein stability may lead to new therapeutic approaches to augment CFTR function. These findings also suggest that generation of a ferret CFTR(ΔF508/ΔF508) animal model may be useful.

Comparative Processing and Function of Human and Ferret Cystic Fibrosis Transmembrane Conductance Regulator*

PubMed Central

Fisher, John T.; Liu, Xiaoming; Yan, Ziying; Luo, Meihui; Zhang, Yulong; Zhou, Weihong; Lee, Ben J.; Song, Yi; Guo, Chenhong; Wang, Yujiong; Lukacs, Gergely L.; Engelhardt, John F.

2012-01-01

The most common cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation is ΔF508, and this causes cystic fibrosis (CF). New CF models in the pig and ferret have been generated that develop lung, pancreatic, liver, and intestinal pathologies that reflect disease in CF patients. Species-specific biology in the processing of CFTR has demonstrated that pig and mouse ΔF508-CFTR proteins are more effectively processed to the apical membrane of airway epithelia than human ΔF508-CFTR. The processing behavior of ferret WT- and ΔF508-CFTR proteins remains unknown, and such information is important to predicting the utility of a ΔF508-CFTR ferret. To this end, we sought to compare processing, membrane stability, and function of human and ferret WT- and ΔF508-CFTR proteins in a heterologous expression system using HT1080, HEK293T, BHK21, and Cos7 cells as well as human and ferret CF polarized airway epithelia. Analysis of the protein processing and stability by metabolic pulse-chase and surface On-Cell Western blots revealed that WT-fCFTR half-life and membrane stability were increased relative to WT-hCFTR. Furthermore, in BHK21, Cos7, and CuFi cells, human and ferret ΔF508-CFTR processing was negligible, whereas low levels of processing of ΔF508-fCFTR could be seen in HT1080 and HEK293T cells. Only the WT-fCFTR, but not ΔF508-fCFTR, produced functional cAMP-inducible chloride currents in both CF human and ferret airway epithelia. Further elucidation of the mechanism responsible for elevated fCFTR protein stability may lead to new therapeutic approaches to augment CFTR function. These findings also suggest that generation of a ferret CFTRΔF508/ΔF508 animal model may be useful. PMID:22570484

Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer

PubMed Central

Patel, Priya; Kato, Tatsuya; Ujiie, Hideki; Wada, Hironobu; Lee, Daiyoon; Hu, Hsin-pei; Hirohashi, Kentaro; Ahn, Jin Young; Zheng, Jinzi; Yasufuku, Kazuhiro

2016-01-01

Background Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice. Methods CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A clinical NIR imaging system (SPY®, Novadaq) was used to measure fluorescence intensity of tumor and lung. Tumor-to-background-ratios (TBR) were calculated in inflated and deflated states. The mean Hounsfield unit (HU) of lung tumor was quantified using the CT data set and a semi-automated threshold-based method. Histological evaluation using H&E, the macrophage marker F4/80 and the endothelial cell marker CD31, was performed, and compared to the liposomal fluorescence signal obtained from adjacent tissue sections Results The fluorescence TBR measured when the lung is in the inflated state (2.0 ± 0.58) was significantly greater than in the deflated state (1.42 ± 0.380 (n = 7, p<0.003). Mean fluorescent signal in tumor was highly variable across samples, (49.0 ± 18.8 AU). CT image analysis revealed greater contrast enhancement in lung tumors (a mean increase of 110 ± 57 HU) when CF800 is administered compared to the no contrast enhanced tumors (p = 0.0002). Conclusion Preliminary data suggests that the high fluorescence TBR and CT tumor contrast enhancement provided by CF800 may have clinical utility in localization of lung cancer during CT and NIR image-guided surgery. PMID:27584018

Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer.

PubMed

Patel, Priya; Kato, Tatsuya; Ujiie, Hideki; Wada, Hironobu; Lee, Daiyoon; Hu, Hsin-Pei; Hirohashi, Kentaro; Ahn, Jin Young; Zheng, Jinzi; Yasufuku, Kazuhiro

2016-01-01

Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice. CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A clinical NIR imaging system (SPY®, Novadaq) was used to measure fluorescence intensity of tumor and lung. Tumor-to-background-ratios (TBR) were calculated in inflated and deflated states. The mean Hounsfield unit (HU) of lung tumor was quantified using the CT data set and a semi-automated threshold-based method. Histological evaluation using H&E, the macrophage marker F4/80 and the endothelial cell marker CD31, was performed, and compared to the liposomal fluorescence signal obtained from adjacent tissue sections. The fluorescence TBR measured when the lung is in the inflated state (2.0 ± 0.58) was significantly greater than in the deflated state (1.42 ± 0.380 (n = 7, p<0.003). Mean fluorescent signal in tumor was highly variable across samples, (49.0 ± 18.8 AU). CT image analysis revealed greater contrast enhancement in lung tumors (a mean increase of 110 ± 57 HU) when CF800 is administered compared to the no contrast enhanced tumors (p = 0.0002). Preliminary data suggests that the high fluorescence TBR and CT tumor contrast enhancement provided by CF800 may have clinical utility in localization of lung cancer during CT and NIR image-guided surgery.

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.

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation.

PubMed

De Stefano, Daniela; Villella, Valeria R; Esposito, Speranza; Tosco, Antonella; Sepe, Angela; De Gregorio, Fabiola; Salvadori, Laura; Grassia, Rosa; Leone, Carlo A; De Rosa, Giuseppe; Maiuri, Maria C; Pettoello-Mantovani, Massimo; Guido, Stefano; Bossi, Anna; Zolin, Anna; Venerando, Andrea; Pinna, Lorenzo A; Mehta, Anil; Bona, Gianni; Kroemer, Guido; Maiuri, Luigi; Raia, Valeria

2014-01-01

Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in Cftr(F508del) homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation.

Stenotrophomonas maltophilia Virulence and Specific Variations in Trace Elements during Acute Lung Infection: Implications in Cystic Fibrosis

PubMed Central

Crocetta, Valentina; Consalvo, Ada; Zappacosta, Roberta; Di Ilio, Carmine; Di Bonaventura, Giovanni

2014-01-01

Metal ions are necessary for the proper functioning of the immune system, and, therefore, they might have a significant influence on the interaction between bacteria and host. Ionic dyshomeostasis has been recently observed also in cystic fibrosis (CF) patients, whose respiratory tract is frequently colonized by Stenotrophomonas maltophilia. For the first time, here we used an inductively mass spectrometry method to perform a spatial and temporal analysis of the pattern of changes in a broad range of major trace elements in response to pulmonary infection by S. maltophilia. To this, DBA/2 mouse lungs were comparatively infected by a CF strain and by an environmental one. Our results showed that pulmonary ionomic profile was significantly affected during infection. Infected mice showed increased lung levels of Mg, P, S, K, Zn, Se, and Rb. To the contrary, Mn, Fe, Co, and Cu levels resulted significantly decreased. Changes of element concentrations were correlated with pulmonary bacterial load and markers of inflammation, and occurred mostly on day 3 post-exposure, when severity of infection culminated. Interestingly, CF strain – significantly more virulent than the environmental one in our murine model - provoked a more significant impact in perturbing pulmonary metal homeostasis. Particularly, exposure to CF strain exclusively increased P and K levels, while decreased Fe and Mn ones. Overall, our data clearly indicate that S. maltophilia modulates pulmonary metal balance in a concerted and virulence-dependent manner highlighting the potential role of the element dyshomeostasis during the progression of S. maltophilia infection, probably exacerbating the harmful effects of the loss of CF transmembrane conductance regulator function. Further investigations are required to understand the biological significance of these alterations and to confirm they are specifically caused by S. maltophilia. PMID:24586389

Expression Analysis of a Highly Adherent and Cytotoxic Small Colony Variant of Pseudomonas aeruginosa Isolated from a Lung of a Patient with Cystic Fibrosis†

PubMed Central

von Götz, Franz; Häussler, Susanne; Jordan, Doris; Saravanamuthu, Senthil Selvan; Wehmhöner, Dirk; Strüßmann, André; Lauber, Joerg; Attree, Ina; Buer, Jan; Tümmler, Burkhard; Steinmetz, Ivo

2004-01-01

The heterogeneous environment of the lung of the cystic fibrosis (CF) patient gives rise to Pseudomonas aeruginosa small colony variants (SCVs) with increased antibiotic resistance, autoaggregative growth behavior, and an enhanced ability to form biofilms. In this study, oligonucleotide DNA microarrays were used to perform a genome-wide expression study of autoaggregative and highly adherent P. aeruginosa SCV 20265 isolated from a CF patient's lung in comparison with its clonal wild type and a revertant generated in vitro from the SCV population. Most strikingly, SCV 20265 showed a pronounced upregulation of the type III protein secretion system (TTSS) and the respective effector proteins. This differential expression was shown to be biologically meaningful, as SCV 20265 and other hyperpiliated and autoaggregative SCVs with increased TTSS expression were significantly more cytotoxic for macrophages in vitro and were more virulent in a mouse model of respiratory tract infection than the wild type. The observed cytotoxicity and virulence of SCV 20265 required exsA, an important transcriptional activator of the TTSS. Thus, the prevailing assumption that P. aeruginosa is subject to selection towards reduced cytotoxicity and attenuated virulence during chronic CF lung infection might not apply to all clonal variants. PMID:15175297

Antiinflammatory and Antimicrobial Effects of Thiocyanate in a Cystic Fibrosis Mouse Model

PubMed Central

Chandler, Joshua D.; Min, Elysia; Huang, Jie; McElroy, Cameron S.; Dickerhof, Nina; Mocatta, Tessa; Fletcher, Ashley A.; Evans, Christopher M.; Liang, Liping; Patel, Manisha; Kettle, Anthony J.; Nichols, David P.

2015-01-01

Thiocyanate (SCN) is used by the innate immune system, but less is known about its impact on inflammation and oxidative stress. Granulocytes oxidize SCN to evolve the bactericidal hypothiocyanous acid, which we previously demonstrated is metabolized by mammalian, but not bacterial, thioredoxin reductase (TrxR). There is also evidence that SCN is dysregulated in cystic fibrosis (CF), a disease marked by chronic infection and airway inflammation. To investigate antiinflammatory effects of SCN, we administered nebulized SCN or saline to β epithelial sodium channel (βENaC) mice, a phenotypic CF model. SCN significantly decreased airway neutrophil infiltrate and restored the redox ratio of glutathione in lung tissue and airway epithelial lining fluid to levels comparable to wild type. Furthermore, in Pseudomonas aeruginosa–infected βENaC and wild-type mice, SCN decreased inflammation, proinflammatory cytokines, and bacterial load. SCN also decreased airway neutrophil chemokine keratinocyte chemoattractant (also known as C-X-C motif chemokine ligand 1) and glutathione sulfonamide, a biomarker of granulocyte oxidative activity, in uninfected βENaC mice. Lung tissue TrxR activity and expression increased in inflamed lung tissue, providing in vivo evidence for the link between hypothiocyanous acid metabolism by TrxR and the promotion of selective biocide of pathogens. SCN treatment both suppressed inflammation and improved host defense, suggesting that nebulized SCN may have important therapeutic utility in diseases of both chronic airway inflammation and persistent bacterial infection, such as CF. PMID:25490247

A statistical model to predict one-year risk of death in patients with cystic fibrosis.

PubMed

Aaron, Shawn D; Stephenson, Anne L; Cameron, Donald W; Whitmore, George A

2015-11-01

We constructed a statistical model to assess the risk of death for cystic fibrosis (CF) patients between scheduled annual clinical visits. Our model includes a CF health index that shows the influence of risk factors on CF chronic health and on the severity and frequency of CF exacerbations. Our study used Canadian CF registry data for 3,794 CF patients born after 1970. Data up to 2010 were analyzed, yielding 44,390 annual visit records. Our stochastic process model postulates that CF health between annual clinical visits is a superposition of chronic disease progression and an exacerbation shock stream. Death occurs when an exacerbation carries CF health across a critical threshold. The data constitute censored survival data, and hence, threshold regression was used to connect CF death to study covariates. Maximum likelihood estimates were used to determine which clinical covariates were included within the regression functions for both CF chronic health and CF exacerbations. Lung function, Pseudomonas aeruginosa infection, CF-related diabetes, weight deficiency, pancreatic insufficiency, and the deltaF508 homozygous mutation were significantly associated with CF chronic health status. Lung function, age, gender, age at CF diagnosis, P aeruginosa infection, body mass index <18.5, number of previous hospitalizations for CF exacerbations in the preceding year, and decline in forced expiratory volume in 1 second in the preceding year were significantly associated with CF exacerbations. When combined in one summative model, the regression functions for CF chronic health and CF exacerbation risk provided a simple clinical scoring tool for assessing 1-year risk of death for an individual CF patient. Goodness-of-fit tests of the model showed very encouraging results. We confirmed predictive validity of the model by comparing actual and estimated deaths in repeated hold-out samples from the data set and showed excellent agreement between estimated and actual mortality. Our threshold regression model incorporates a composite CF chronic health status index and an exacerbation risk index to produce an accurate clinical scoring tool for prediction of 1-year survival of CF patients. Our tool can be used by clinicians to decide on optimal timing for lung transplant referral. Copyright © 2015 Elsevier Inc. All rights reserved.

Targeting autophagy as a novel strategy for facilitating the therapeutic action of potentiators on ΔF508 cystic fibrosis transmembrane conductance regulator

PubMed Central

Luciani, Alessandro; Villella, Valeria Rachela; Esposito, Speranza; Gavina, Manuela; Russo, Ilaria; Silano, Marco; Guido, Stefano; Pettoello-Mantovani, Massimo; Carnuccio, Rosa; Scholte, Bob; De Matteis, Antonella; Maiuri, Maria Chiara; Raia, Valeria; Luini, Alberto; Kroemer, Guido; Maiuri, Luigi

2012-01-01

Channel activators (potentiators) of cystic fibrosis (CF) transmembrane conductance regulator (CFTR), can be used for the treatment of the small subset of CF patients that carry plasma membrane-resident CFTR mutants. However, approximately 90% of CF patients carry the misfolded ΔF508-CFTR and are poorly responsive to potentiators, because ΔF508-CFTR is intrinsically unstable at the plasma membrane (PM) even if rescued by pharmacological correctors. We have demonstrated that human and mouse CF airways are autophagy deficient due to functional sequestration of BECN1 and that the tissue transglutaminase-2 inhibitor, cystamine, or antioxidants restore BECN1-dependent autophagy and reduce SQSTM1/p62 levels, thus favoring ΔF508-CFTR trafficking to the epithelial surface. Here, we investigated whether these treatments could facilitate the beneficial action of potentiators on ΔF508-CFTR homozygous airways. Cystamine or the superoxide dismutase (SOD)/catalase-mimetic EUK-134 stabilized ΔF508-CFTR at the plasma membrane of airway epithelial cells and sustained the expression of CFTR at the epithelial surface well beyond drug withdrawal, overexpressing BECN1 and depleting SQSTM1. This facilitates the beneficial action of potentiators in controlling inflammation in ex vivo ΔF508-CFTR homozygous human nasal biopsies and in vivo in mouse ΔF508-CFTR lungs. Direct depletion of Sqstm1 by shRNAs in vivo in ΔF508-CFTR mice synergized with potentiators in sustaining surface CFTR expression and suppressing inflammation. Cystamine pre-treatment restored ΔF508-CFTR response to the CFTR potentiators genistein, Vrx-532 or Vrx-770 in freshly isolated brushed nasal epithelial cells from ΔF508-CFTR homozygous patients. These findings delineate a novel therapeutic strategy for the treatment of CF patients with the ΔF508-CFTR mutation in which patients are first treated with cystamine and subsequently pulsed with CFTR potentiators. PMID:22874563

Targeting autophagy as a novel strategy for facilitating the therapeutic action of potentiators on ΔF508 cystic fibrosis transmembrane conductance regulator.

PubMed

Luciani, Alessandro; Villella, Valeria Rachela; Esposito, Speranza; Gavina, Manuela; Russo, Ilaria; Silano, Marco; Guido, Stefano; Pettoello-Mantovani, Massimo; Carnuccio, Rosa; Scholte, Bob; De Matteis, Antonella; Maiuri, Maria Chiara; Raia, Valeria; Luini, Alberto; Kroemer, Guido; Maiuri, Luigi

2012-11-01

Channel activators (potentiators) of cystic fibrosis (CF) transmembrane conductance regulator (CFTR), can be used for the treatment of the small subset of CF patients that carry plasma membrane-resident CFTR mutants. However, approximately 90% of CF patients carry the misfolded ΔF508-CFTR and are poorly responsive to potentiators, because ΔF508-CFTR is intrinsically unstable at the plasma membrane (PM) even if rescued by pharmacological correctors. We have demonstrated that human and mouse CF airways are autophagy deficient due to functional sequestration of BECN1 and that the tissue transglutaminase-2 inhibitor, cystamine, or antioxidants restore BECN1-dependent autophagy and reduce SQSTM1/p62 levels, thus favoring ΔF508-CFTR trafficking to the epithelial surface. Here, we investigated whether these treatments could facilitate the beneficial action of potentiators on ΔF508-CFTR homozygous airways. Cystamine or the superoxide dismutase (SOD)/catalase-mimetic EUK-134 stabilized ΔF508-CFTR at the plasma membrane of airway epithelial cells and sustained the expression of CFTR at the epithelial surface well beyond drug withdrawal, overexpressing BECN1 and depleting SQSTM1. This facilitates the beneficial action of potentiators in controlling inflammation in ex vivo ΔF508-CFTR homozygous human nasal biopsies and in vivo in mouse ΔF508-CFTR lungs. Direct depletion of Sqstm1 by shRNAs in vivo in ΔF508-CFTR mice synergized with potentiators in sustaining surface CFTR expression and suppressing inflammation. Cystamine pre-treatment restored ΔF508-CFTR response to the CFTR potentiators genistein, Vrx-532 or Vrx-770 in freshly isolated brushed nasal epithelial cells from ΔF508-CFTR homozygous patients. These findings delineate a novel therapeutic strategy for the treatment of CF patients with the ΔF508-CFTR mutation in which patients are first treated with cystamine and subsequently pulsed with CFTR potentiators.

Animal models of gastrointestinal and liver diseases. Animal models of cystic fibrosis: gastrointestinal, pancreatic, and hepatobiliary disease and pathophysiology

PubMed Central

Olivier, Alicia K.; Gibson-Corley, Katherine N.

2015-01-01

Multiple organ systems, including the gastrointestinal tract, pancreas, and hepatobiliary systems, are affected by cystic fibrosis (CF). Many of these changes begin early in life and are difficult to study in young CF patients. Recent development of novel CF animal models has expanded opportunities in the field to better understand CF pathogenesis and evaluate traditional and innovative therapeutics. In this review, we discuss manifestations of CF disease in gastrointestinal, pancreatic, and hepatobiliary systems of humans and animal models. We also compare the similarities and limitations of animal models and discuss future directions for modeling CF. PMID:25591863

Systemic Nicotine Increases Gain and Narrows Receptive Fields in A1 via Integrated Cortical and Subcortical Actions

PubMed Central

Intskirveli, Irakli

2017-01-01

Abstract Nicotine enhances sensory and cognitive processing via actions at nicotinic acetylcholine receptors (nAChRs), yet the precise circuit- and systems-level mechanisms remain unclear. In sensory cortex, nicotinic modulation of receptive fields (RFs) provides a model to probe mechanisms by which nAChRs regulate cortical circuits. Here, we examine RF modulation in mouse primary auditory cortex (A1) using a novel electrophysiological approach: current-source density (CSD) analysis of responses to tone-in-notched-noise (TINN) acoustic stimuli. TINN stimuli consist of a tone at the characteristic frequency (CF) of the recording site embedded within a white noise stimulus filtered to create a spectral “notch” of variable width centered on CF. Systemic nicotine (2.1 mg/kg) enhanced responses to the CF tone and to narrow-notch stimuli, yet reduced the response to wider-notch stimuli, indicating increased response gain within a narrowed RF. Subsequent manipulations showed that modulation of cortical RFs by systemic nicotine reflected effects at several levels in the auditory pathway: nicotine suppressed responses in the auditory midbrain and thalamus, with suppression increasing with spectral distance from CF so that RFs became narrower, and facilitated responses in the thalamocortical pathway, while nicotinic actions within A1 further contributed to both suppression and facilitation. Thus, multiple effects of systemic nicotine integrate along the ascending auditory pathway. These actions at nAChRs in cortical and subcortical circuits, which mimic effects of auditory attention, likely contribute to nicotinic enhancement of sensory and cognitive processing. PMID:28660244

Systemic Nicotine Increases Gain and Narrows Receptive Fields in A1 via Integrated Cortical and Subcortical Actions.

PubMed

Askew, Caitlin; Intskirveli, Irakli; Metherate, Raju

2017-01-01

Nicotine enhances sensory and cognitive processing via actions at nicotinic acetylcholine receptors (nAChRs), yet the precise circuit- and systems-level mechanisms remain unclear. In sensory cortex, nicotinic modulation of receptive fields (RFs) provides a model to probe mechanisms by which nAChRs regulate cortical circuits. Here, we examine RF modulation in mouse primary auditory cortex (A1) using a novel electrophysiological approach: current-source density (CSD) analysis of responses to tone-in-notched-noise (TINN) acoustic stimuli. TINN stimuli consist of a tone at the characteristic frequency (CF) of the recording site embedded within a white noise stimulus filtered to create a spectral "notch" of variable width centered on CF. Systemic nicotine (2.1 mg/kg) enhanced responses to the CF tone and to narrow-notch stimuli, yet reduced the response to wider-notch stimuli, indicating increased response gain within a narrowed RF. Subsequent manipulations showed that modulation of cortical RFs by systemic nicotine reflected effects at several levels in the auditory pathway: nicotine suppressed responses in the auditory midbrain and thalamus, with suppression increasing with spectral distance from CF so that RFs became narrower, and facilitated responses in the thalamocortical pathway, while nicotinic actions within A1 further contributed to both suppression and facilitation. Thus, multiple effects of systemic nicotine integrate along the ascending auditory pathway. These actions at nAChRs in cortical and subcortical circuits, which mimic effects of auditory attention, likely contribute to nicotinic enhancement of sensory and cognitive processing.

Dual activation of CFTR and CLCN2 by lubiprostone in murine nasal epithelia.

PubMed

Schiffhauer, Eric S; Vij, Neeraj; Kovbasnjuk, Olga; Kang, Po Wei; Walker, Doug; Lee, Seakwoo; Zeitlin, Pamela L

2013-03-01

Multiple sodium and chloride channels on the apical surface of nasal epithelial cells contribute to periciliary fluid homeostasis, a function that is disrupted in patients with cystic fibrosis (CF). Among these channels is the chloride channel CLCN2, which has been studied as a potential alternative chloride efflux pathway in the absence of CFTR. The object of the present study was to use the nasal potential difference test (NPD) to quantify CLCN2 function in an epithelial-directed TetOn CLCN2 transgenic mouse model (TGN-K18rtTA-hCLCN2) by using the putative CLCN2 pharmacological agonist lubiprostone and peptide inhibitor GaTx2. Lubiprostone significantly increased chloride transport in the CLCN2-overexpressing mice following activation of the transgene by doxycycline. This response to lubiprostone was significantly inhibited by GaTx2 after CLCN2 activation in TGN-CLCN2 mice. Cftr(-/-) and Clc2(-/-) mice showed hyperpolarization indicative of chloride efflux in response to lubiprostone, which was fully inhibited by GaTx2 and CFTR inhibitor 172 + GlyH-101, respectively. Our study reveals lubiprostone as a pharmacological activator of both CFTR and CLCN2. Overexpression and activation of CLCN2 leads to improved mouse NPD readings, suggesting it is available as an alternative pathway for epithelial chloride secretion in murine airways. The utilization of CLCN2 as an alternative chloride efflux channel could provide clinical benefit to patients with CF, especially if the pharmacological activator is administered as an aerosol.

Cystic fibrosis transmembrane regulator gene (CFTR) is associated with abnormal enamel formation.

PubMed

Arquitt, C K; Boyd, C; Wright, J T

2002-07-01

Cystic fibrosis (CF), a chloride ion transport disorder, is caused by mutations of the cftr gene and is the most common autosomal-recessive heritable disease in Caucasians. CFTR knockout mice have enamel with crystallite defects, retained protein, and hypomineralization, suggesting a role for CFTR in enamel formation and mineralization. This investigation examined CFTR expression and elemental composition in developing murine incisor teeth. RT-PCR showed cftr mRNA expression in the normal mouse apical incisor tissue but not in the CFTR knockout tissue. Elemental analysis by energy-dispersive x-ray spectroscopy showed relatively decreased chloride in secretory-stage CF enamel. Iron and potassium were significantly increased, and calcium was significantly decreased (p value = 0.05) in the CF mature enamel. Abnormal enamel mineralization, ion concentrations, and molecular evidence of cftr mRNA expression by odontogenic cells strongly suggest that CFTR plays an important role in enamel formation.

Role of Mutant CFTR in Hypersusceptibility of Cystic Fibrosis Patients to Lung Infections

NASA Astrophysics Data System (ADS)

Pier, Gerald B.; Grout, Martha; Zaidi, Tanweer S.; Olsen, John C.; Johnson, Larry G.; Yankaskas, James R.; Goldberg, Joanna B.

1996-01-01

Cystic fibrosis (CF) patients are hypersusceptible to chronic Pseudomonas aeruginosa lung infections. Cultured human airway epithelial cells expressing the ΔF508 allele of the cystic fibrosis transmembrane conductance regulator (CFTR) were defective in uptake of P. aeruginosa compared with cells expressing the wild-type allele. Pseudomonas aeruginosa lipopolysaccharide (LPS)-core oligosaccharide was identified as the bacterial ligand for epithelial cell ingestion; exogenous oligosaccharide inhibited bacterial ingestion in a neonatal mouse model, resulting in increased amounts of bacteria in the lungs. CFTR may contribute to a host-defense mechanism that is important for clearance of P. aeruginosa from the respiratory tract.

Hepatocyte nuclear factor 4alpha contributes to thyroid hormone homeostasis by cooperatively regulating the type 1 iodothyronine deiodinase gene with GATA4 and Kruppel-like transcription factor 9.

PubMed

Ohguchi, Hiroto; Tanaka, Toshiya; Uchida, Aoi; Magoori, Kenta; Kudo, Hiromi; Kim, Insook; Daigo, Kenji; Sakakibara, Iori; Okamura, Masashi; Harigae, Hideo; Sasaki, Takeshi; Osborne, Timothy F; Gonzalez, Frank J; Hamakubo, Takao; Kodama, Tatsuhiko; Sakai, Juro

2008-06-01

Type 1 iodothyronine deiodinase (Dio1), a selenoenzyme catalyzing the bioactivation of thyroid hormone, is highly expressed in the liver. Dio1 mRNA and enzyme activity levels are markedly reduced in the livers of hepatocyte nuclear factor 4alpha (HNF4alpha)-null mice, thus accounting for its liver-specific expression. Consistent with this deficiency, serum T4 and rT3 concentrations are elevated in these mice compared with those in HNF4alpha-floxed control littermates; however, serum T3 levels are unchanged. Promoter analysis of the mouse Dio1 gene demonstrated that HNF4alpha plays a key role in the transactivation of the mouse Dio1 gene. Deletion and substitution mutation analyses demonstrated that a proximal HNF4alpha site (direct repeat 1 [TGGACAAAGGTGC]; HNF4alpha-RE) is crucial for transactivation of the mouse Dio1 gene by HNF4alpha. Mouse Dio1 is also stimulated by thyroid hormone signaling, but a direct role for thyroid hormone receptor action has not been reported. We also showed that thyroid hormone-inducible Krüppel-like factor 9 (KLF9) stimulates the mouse Dio1 promoter very efficiently through two CACCC sequences that are located on either side of HNF4alpha-RE. Furthermore, KLF9 functions together with HNF4alpha and GATA4 to synergistically activate the mouse Dio1 promoter, suggesting that Dio1 is regulated by thyroid hormone in the mouse through an indirect mechanism requiring prior KLF9 induction. In addition, we showed that physical interactions between the C-terminal zinc finger domain (Cf) of GATA4 and activation function 2 of HNF4alpha and between the basic domain adjacent to Cf of GATA4 and a C-terminal domain of KLF9 are both required for this synergistic response. Taken together, these results suggest that HNF4alpha regulates thyroid hormone homeostasis through transcriptional regulation of the mouse Dio1 gene with GATA4 and KLF9.

Hepatocyte Nuclear Factor 4α Contributes to Thyroid Hormone Homeostasis by Cooperatively Regulating the Type 1 Iodothyronine Deiodinase Gene with GATA4 and Krüppel-Like Transcription Factor 9▿ †

PubMed Central

Ohguchi, Hiroto; Tanaka, Toshiya; Uchida, Aoi; Magoori, Kenta; Kudo, Hiromi; Kim, Insook; Daigo, Kenji; Sakakibara, Iori; Okamura, Masashi; Harigae, Hideo; Sasaki, Takeshi; Osborne, Timothy F.; Gonzalez, Frank J.; Hamakubo, Takao; Kodama, Tatsuhiko; Sakai, Juro

2008-01-01

Type 1 iodothyronine deiodinase (Dio1), a selenoenzyme catalyzing the bioactivation of thyroid hormone, is highly expressed in the liver. Dio1 mRNA and enzyme activity levels are markedly reduced in the livers of hepatocyte nuclear factor 4α (HNF4α)-null mice, thus accounting for its liver-specific expression. Consistent with this deficiency, serum T4 and rT3 concentrations are elevated in these mice compared with those in HNF4α-floxed control littermates; however, serum T3 levels are unchanged. Promoter analysis of the mouse Dio1 gene demonstrated that HNF4α plays a key role in the transactivation of the mouse Dio1 gene. Deletion and substitution mutation analyses demonstrated that a proximal HNF4α site (direct repeat 1 [TGGACAAAGGTGC]; HNF4α-RE) is crucial for transactivation of the mouse Dio1 gene by HNF4α. Mouse Dio1 is also stimulated by thyroid hormone signaling, but a direct role for thyroid hormone receptor action has not been reported. We also showed that thyroid hormone-inducible Krüppel-like factor 9 (KLF9) stimulates the mouse Dio1 promoter very efficiently through two CACCC sequences that are located on either side of HNF4α-RE. Furthermore, KLF9 functions together with HNF4α and GATA4 to synergistically activate the mouse Dio1 promoter, suggesting that Dio1 is regulated by thyroid hormone in the mouse through an indirect mechanism requiring prior KLF9 induction. In addition, we showed that physical interactions between the C-terminal zinc finger domain (Cf) of GATA4 and activation function 2 of HNF4α and between the basic domain adjacent to Cf of GATA4 and a C-terminal domain of KLF9 are both required for this synergistic response. Taken together, these results suggest that HNF4α regulates thyroid hormone homeostasis through transcriptional regulation of the mouse Dio1 gene with GATA4 and KLF9. PMID:18426912

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation

PubMed Central

Stefano, Daniela De; Villella, Valeria R; Esposito, Speranza; Tosco, Antonella; Sepe, Angela; Gregorio, Fabiola De; Salvadori, Laura; Grassia, Rosa; Leone, Carlo A; Rosa, Giuseppe De; Maiuri, Maria C; Pettoello-Mantovani, Massimo; Guido, Stefano; Bossi, Anna; Zolin, Anna; Venerando, Andrea; Pinna, Lorenzo A; Mehta, Anil; Bona, Gianni; Kroemer, Guido; Maiuri, Luigi; Raia, Valeria

2014-01-01

Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in CftrF508del homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation. PMID:25350163

Dual activation of CFTR and CLCN2 by lubiprostone in murine nasal epithelia

PubMed Central

Schiffhauer, Eric S.; Vij, Neeraj; Kovbasnjuk, Olga; Kang, Po Wei; Walker, Doug; Lee, Seakwoo

2013-01-01

Multiple sodium and chloride channels on the apical surface of nasal epithelial cells contribute to periciliary fluid homeostasis, a function that is disrupted in patients with cystic fibrosis (CF). Among these channels is the chloride channel CLCN2, which has been studied as a potential alternative chloride efflux pathway in the absence of CFTR. The object of the present study was to use the nasal potential difference test (NPD) to quantify CLCN2 function in an epithelial-directed TetOn CLCN2 transgenic mouse model (TGN-K18rtTA-hCLCN2) by using the putative CLCN2 pharmacological agonist lubiprostone and peptide inhibitor GaTx2. Lubiprostone significantly increased chloride transport in the CLCN2-overexpressing mice following activation of the transgene by doxycycline. This response to lubiprostone was significantly inhibited by GaTx2 after CLCN2 activation in TGN-CLCN2 mice. Cftr−/− and Clc2−/− mice showed hyperpolarization indicative of chloride efflux in response to lubiprostone, which was fully inhibited by GaTx2 and CFTR inhibitor 172 + GlyH-101, respectively. Our study reveals lubiprostone as a pharmacological activator of both CFTR and CLCN2. Overexpression and activation of CLCN2 leads to improved mouse NPD readings, suggesting it is available as an alternative pathway for epithelial chloride secretion in murine airways. The utilization of CLCN2 as an alternative chloride efflux channel could provide clinical benefit to patients with CF, especially if the pharmacological activator is administered as an aerosol. PMID:23316067

Prodrugs of herpes simplex thymidine kinase inhibitors.

PubMed

Yanachkova, Milka; Xu, Wei-Chu; Dvoskin, Sofya; Dix, Edward J; Yanachkov, Ivan B; Focher, Federico; Savi, Lida; Sanchez, M Dulfary; Foster, Timothy P; Wright, George E

2015-04-01

Because guanine-based herpes simplex virus thymidine kinase inhibitors are not orally available, we synthesized various 6-deoxy prodrugs of these compounds and evaluated them with regard to solubility in water, oral bioavailability, and efficacy to prevent herpes simplex virus-1 reactivation from latency in a mouse model. Organic synthesis was used to prepare compounds, High Performance Liquid Chromatography (HPLC) to analyze hydrolytic conversion, Mass Spectrometry (MS) to measure oral bioavailability, and mouse latent infection and induced reactivation to evaluate the efficacy of a specific prodrug. Aqueous solubilities of prodrugs were improved, oxidation of prodrugs by animal cytosols occurred in vitro, and oral absorption of the optimal prodrug sacrovir™ (6-deoxy-mCF3PG) in the presence of the aqueous adjuvant Soluplus® and conversion to active compound N(2)-[3-(trifluoromethyl)pheny])guanine (mCF3PG) were accomplished in mice. Treatment of herpes simplex virus-1 latent mice with sacrovir™ in 1% Soluplus in drinking water significantly suppressed herpes simplex virus-1 reactivation and viral genomic replication. Ad libitum oral delivery of sacrovir™ was effective in suppressing herpes simplex virus-1 reactivation in ocularly infected latent mice as measured by the numbers of mice shedding infectious virus at the ocular surface, numbers of trigeminal ganglia positive for infectious virus, number of corneas that had detectable infectious virus, and herpes simplex virus-1 genome copy numbers in trigeminal ganglia following reactivation. These results demonstrate the statistically significant effect of the prodrug on suppressing herpes simplex virus-1 reactivation in vivo. © The Author(s) 2015.

Matrix metalloproteinase expression and activity in trophoblast-decidual tissues at organogenesis in CF-1 mouse.

PubMed

Fontana, Vanina; Coll, Tamara A; Sobarzo, Cristian M A; Tito, Leticia Perez; Calvo, Juan Carlos; Cebral, Elisa

2012-10-01

During early placentation, matrix metalloproteinases (MMPs) play important roles in decidualization, trophoblast migration, invasion, angiogenesis, vascularization and extracellular matrix (ECM) remodeling of the endometrium. The aim of our study was to analyze the localization, distribution and differential expression of MMP-2 and -9 in the organogenic implantation site and to evaluate in vivo and in vitro decidual MMP-2 and -9 activities on day 10 of gestation in CF-1 mouse. Whole extracts for Western blotting of organogenic E10-decidua expressed MMP-2 and -9 isoforms. MMP-2 immunoreactivity was found in a granular and discrete pattern in ECM of mesometrial decidua (MD) near maternal blood vessels and slightly in non-decidualized endometrium (NDE). Immunoexpression of MMP-9 was also detected in NDE, in cytoplasm of decidual cells and ECM of vascular MD, in trophoblastic area and in growing antimesometrial deciduum. Gelatin zymography showed that MMP-9 activity was significantly lower in CM compared to the active form of direct (not cultured) and cultured decidua. The decidual active MMP-9 was significantly higher than the active MMP-2. These results show differential localization, protein expression and enzymatic activation of MMPs, suggesting specific roles for MMP-2 and MMP-9 in decidual and trophoblast tissues related to organogenic ECM remodeling and vascularization during early establishment of mouse placentation.

Cystic fibrosis transmembrane conductance regulator regulates epithelial cell response to Aspergillus and resultant pulmonary inflammation.

PubMed

Chaudhary, Neelkamal; Datta, Kausik; Askin, Frederic B; Staab, Janet F; Marr, Kieren A

2012-02-01

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) alter epithelial cell (EC) interactions with multiple microbes, such that dysregulated inflammation and injury occur with airway colonization in people with cystic fibrosis (CF). Aspergillus fumigatus frequently colonizes CF airways, but it has been assumed to be an innocent saprophyte; its potential role as a cause of lung disease is controversial. To study the interactions between Aspergillus and EC, and the role of the fungus in evoking inflammatory responses. A. fumigatus expressing green fluorescent protein was developed for in vitro and in vivo models, which used cell lines and mouse tracheal EC. Fungal spores (conidia) are rapidly ingested by ECs derived from bronchial cell lines and murine tracheas, supporting a role for EC in early airway clearance. Bronchial ECs harboring CFTR mutations (ΔF508) or deletion demonstrate impaired uptake and killing of conidia, and ECs with CFTR mutation undergo more conidial-induced apoptosis. Germinated (hyphal) forms of the fungus evoke secretion of inflammatory mediators, with CFTR mutation resulting in increased airway levels of macrophage inflammatory protein 2 and KC, and higher lung monocyte chemotactic protein-1. After A. fumigatus inhalation, CFTR(-/-) mice develop exaggerated lymphocytic inflammation, mucin accumulation, and lung injury. Data demonstrate a critical role for CFTR in mediating EC responses to A. fumigatus. Results suggest that the fungus elicits aberrant pulmonary inflammation in the setting of CFTR mutation, supporting the potential role of antifungals to halt progressive CF lung disease.

What does low-intensity rTMS do to the cerebellum?

PubMed

Morellini, N; Grehl, S; Tang, A; Rodger, J; Mariani, J; Lohof, A M; Sherrard, R M

2015-02-01

Non-invasive stimulation of the human cerebellum, such as by transcranial magnetic stimulation (TMS), is increasingly used to investigate cerebellar function and identify potential treatment for cerebellar dysfunction. However, the effects of TMS on cerebellar neurons remain poorly defined. We applied low-intensity repetitive TMS (LI-rTMS) to the mouse cerebellum in vivo and in vitro and examined the cellular and molecular sequelae. In normal C57/Bl6 mice, 4 weeks of LI-rTMS using a complex biomimetic high-frequency stimulation (BHFS) alters Purkinje cell (PC) dendritic and spine morphology; the effects persist 4 weeks after the end of stimulation. We then evaluated whether LI-rTMS could induce climbing fibre (CF) reinnervation to denervated PCs. After unilateral pedunculotomy in adult mice and 2 weeks sham or BHFS stimulation, VGLUT2 immunohistochemistry was used to quantify CF reinnervation. In contrast to sham, LI-rTMS induced CF reinnervation to the denervated hemicerebellum. To examine potential mechanisms underlying the LI-rTMS effect, we verified that BHFS could induce CF reinnervation using our in vitro olivocerebellar explants in which denervated cerebellar tissue is co-cultured adjacent to intact cerebella and treated with brain-derived neurotrophic factor (BDNF) (as a positive control), sham or LI-rTMS for 2 weeks. Compared with sham, BDNF and BHFS LI-rTMS significantly increased CF reinnervation, without additive effect. To identify potential underlying mechanisms, we examined intracellular calcium flux during the 10-min stimulation. Complex high-frequency stimulation increased intracellular calcium by release from intracellular stores. Thus, even at low intensity, rTMS modifies PC structure and induces CF reinnervation.

Survival in Patients with Advanced Non-cystic Fibrosis Bronchiectasis Versus Cystic Fibrosis on the Waitlist for Lung Transplantation.

PubMed

Hayes, Don; Kopp, Benjamin T; Tobias, Joseph D; Woodley, Frederick W; Mansour, Heidi M; Tumin, Dmitry; Kirkby, Stephen E

2015-12-01

Survival in non-cystic fibrosis (CF) bronchiectasis is not well studied. The United Network for Organ Sharing database was queried from 1987 to 2013 to compare survival in adult patients with non-CF bronchiectasis to patients with CF listed for lung transplantation (LTx). Each subject was tracked from waitlist entry date until death or censoring to determine survival differences between the two groups. Of 2112 listed lung transplant candidates with bronchiectasis (180 non-CF, 1932 CF), 1617 were used for univariate Cox and Kaplan-Meier survival function analysis, 1173 for multivariate Cox models, and 182 for matched-pairs analysis based on propensity scores. Compared to CF, patients with non-CF bronchiectasis had a significantly lower mortality by univariate Cox analysis (HR 0.565; 95 % CI 0.424, 0.754; p < 0.001). Adjusting for potential confounders, multivariate Cox models identified a significant reduction in risk for death associated with non-CF bronchiectasis who were lung transplant candidates (HR 0.684; 95 % CI 0.475, 0.985; p = 0.041). Results were consistent in multivariate models adjusting for pulmonary hypertension and forced expiratory volume in one second. Non-CF bronchiectasis with advanced lung disease was associated with significantly lower mortality hazard compared to CF bronchiectasis on the waitlist for LTx. Separate referral and listing criteria for LTx in non-CF and CF populations should be considered.

Pharmacological analysis of epithelial chloride secretion mechanisms in adult murine airways.

PubMed

Gianotti, Ambra; Ferrera, Loretta; Philp, Amber R; Caci, Emanuela; Zegarra-Moran, Olga; Galietta, Luis J V; Flores, Carlos A

2016-06-15

Defective epithelial chloride secretion occurs in humans with cystic fibrosis (CF), a genetic defect due to loss of function of CFTR, a cAMP-activated chloride channel. In the airways, absence of an active CFTR causes a severe lung disease. In mice, genetic ablation of CFTR function does not result in similar lung pathology. This may be due to the expression of an alternative chloride channel which is activated by calcium. The most probable protein performing this function is TMEM16A, a calcium-activated chloride channel (CaCC). Our aim was to assess the relative contribution of CFTR and TMEM16A to chloride secretion in adult mouse trachea. For this purpose we tested pharmacological inhibitors of chloride channels in normal and CF mice. The amplitude of the cAMP-activated current was similar in both types of animals and was not affected by a selective CFTR inhibitor. In contrast, a CaCC inhibitor (CaCCinh-A01) strongly blocked the cAMP-activated current as well as the calcium-activated chloride secretion triggered by apical UTP. Although control experiments revealed that CaCCinh-A01 also shows inhibitory activity on CFTR, our results indicate that transepithelial chloride secretion in adult mouse trachea is independent of CFTR and that another channel, possibly TMEM16A, performs both cAMP- and calcium-activated chloride transport. The prevalent function of a non-CFTR channel may explain the absence of a defect in chloride transport in CF mice. Copyright © 2016. Published by Elsevier B.V.

5'-adenosine monophosphate mediated cooling treatment enhances ΔF508-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) stability in vivo.

PubMed

Zhang, Yueqiang; O'Brien, William G; Zhao, Zhaoyang; Lee, Cheng Chi

2015-09-04

Gene mutations that produce misprocessed proteins are linked to many human disorders. Interestingly, some misprocessed proteins retained their biological function when stabilized by low temperature treatment of cultured cells in vitro. Here we investigate whether low temperature treatment in vivo can rescue misfolded proteins by applying 5'-AMP mediated whole body cooling to a Cystic Fibrosis (CF) mouse model carrying a mutant cystic fibrosis transmembrane conductance regulator (CFTR) with a deletion of the phenylalanine residue in position 508 (ΔF508-CFTR). Low temperature treatment of cultured cells was previously shown to be able to alleviate the processing defect of ΔF508-CFTR, enhancing its plasma membrane localization and its function in mediating chloride ion transport. Here, we report that whole body cooling enhanced the retention of ΔF508-CFTR in intestinal epithelial cells. Functional analysis based on β-adrenergic dependent salivary secretion and post-natal mortality rate revealed a moderate but significant improvement in treated compared with untreated CF mice. Our findings demonstrate that temperature sensitive processing of mutant proteins can be responsive to low temperature treatment in vivo.

TG2 regulates the heat-shock response by the post-translational modification of HSF1.

PubMed

Rossin, Federica; Villella, Valeria Rachela; D'Eletto, Manuela; Farrace, Maria Grazia; Esposito, Speranza; Ferrari, Eleonora; Monzani, Romina; Occhigrossi, Luca; Pagliarini, Vittoria; Sette, Claudio; Cozza, Giorgio; Barlev, Nikolai A; Falasca, Laura; Fimia, Gian Maria; Kroemer, Guido; Raia, Valeria; Maiuri, Luigi; Piacentini, Mauro

2018-05-11

Heat-shock factor 1 (HSF1) is the master transcription factor that regulates the response to proteotoxic stress by controlling the transcription of many stress-responsive genes including the heat-shock proteins. Here, we show a novel molecular mechanism controlling the activation of HSF1. We demonstrate that transglutaminase type 2 (TG2), dependent on its protein disulphide isomerase activity, triggers the trimerization and activation of HSF1 regulating adaptation to stress and proteostasis impairment. In particular, we find that TG2 loss of function correlates with a defect in the nuclear translocation of HSF1 and in its DNA-binding ability to the HSP70 promoter. We show that the inhibition of TG2 restores the unbalance in HSF1-HSP70 pathway in cystic fibrosis (CF), a human disorder characterized by deregulation of proteostasis. The absence of TG2 leads to an increase of about 40% in CFTR function in a new experimental CF mouse model lacking TG2. Altogether, these results indicate that TG2 plays a key role in the regulation of cellular proteostasis under stressful cellular conditions through the modulation of the heat-shock response. © 2018 The Authors.

Cftr gene targeting in mouse embryonic stem cells mediated by Small Fragment Homologous Replacement (SFHR).

PubMed

Sangiuolo, Federica; Scaldaferri, Maria Lucia; Filareto, Antonio; Spitalieri, Paola; Guerra, Lorenzo; Favia, Maria; Caroppo, Rosa; Mango, Ruggiero; Bruscia, Emanuela; Gruenert, Dieter C; Casavola, Valeria; De Felici, Massimo; Novelli, Giuseppe

2008-01-01

Different gene targeting approaches have been developed to modify endogenous genomic DNA in both human and mouse cells. Briefly, the process involves the targeting of a specific mutation in situ leading to the gene correction and the restoration of a normal gene function. Most of these protocols with therapeutic potential are oligonucleotide based, and rely on endogenous enzymatic pathways. One gene targeting approach, "Small Fragment Homologous Replacement (SFHR)", has been found to be effective in modifying genomic DNA. This approach uses small DNA fragments (SDF) to target specific genomic loci and induce sequence and subsequent phenotypic alterations. This study shows that SFHR can stably introduce a 3-bp deletion (deltaF508, the most frequent cystic fibrosis (CF) mutation) into the Cftr (CF Transmembrane Conductance Regulator) locus in the mouse embryonic stem (ES) cell genome. After transfection of deltaF508-SDF into murine ES cells, SFHR-mediated modification was evaluated at the molecular levels on DNA and mRNA obtained from transfected ES cells. About 12% of transcript corresponding to deleted allele was detected, while 60% of the electroporated cells completely lost any measurable CFTR-dependent chloride efflux. The data indicate that the SFHR technique can be used to effectively target and modify genomic sequences in ES cells. Once the SFHR-modified ES cells differentiate into different cell lineages they can be useful for elucidating tissue-specific gene function and for the development of transplantation-based cellular and therapeutic protocols.

A three-dimensional model of the atmospheric chemistry of E and Z-CF3CH=CHCl (HCFO-1233(zd) (E/Z))

NASA Astrophysics Data System (ADS)

Sulbaek Andersen, Mads P.; Schmidt, Johan A.; Volkova, Aleksandra; Wuebbles, Donald J.

2018-04-01

Using a 3-dimensional global atmospheric chemistry and transport model we investigated the atmospheric degradation of HCFO-1233zd(E), E-CF3CH=CHCl, a commercially important, new hydrofluorocarbon replacement compound. Atmospheric degradation of E-CF3CH=CHCl is initiated by reaction with OH radicals, which leads to several chemical oxidation products. Dissemination of these oxidation products to the environment is of concern due to the possible formation of trifluoroacetic acid (TFA) as a degradation product. The model indicates that the average global yield of TFA from atmospheric processing of E-CF3CH=CHCl is approximately 2%. The annually averaged atmospheric lifetime of E-CF3CH=CHCl was found to be approximately 36 days (12 days for Z-CF3CH=CHCl). As E-CF3CH=CHCl is short lived, by far the majority of its Cl atoms will be released and deposited in the lower atmosphere, and the impact on stratospheric ozone is insignificant. An Ozone Depletion Potential of 0.00030 was determined. The Photochemical Ozone Creation Potential was evaluated and a value of 3.6 determined. Finally, we derive a Global Warming Potential for E-CF3CH=CHCl for a 100 year time horizon of <5. For comparison, data for the stereoismeric analogue, Z-CF3CH=CHCl, was also obtained from the model.

The effect of olanzapine pretreatment on acute cocaine toxicity in mice.

PubMed

Heard, Kennon J; Cleveland, Nathan R; Krier, Shay

2009-07-01

Acute cocaine poisoning causes neuroexcitation and can be fatal. The toxic effects of cocaine can be attenuated by antagonists of serotonin, muscarinic cholinergic, and dopamine receptors. Olanzapine, an atypical antipsychotic medication, is an antagonist of these receptors. The objective of this study is to evaluate the efficacy of olanzapine pretreatment for attenuation of acute cocaine toxicity using a mouse model. Eighty male CF-1 mice were randomly assigned to olanzapine (1 mg/kg) or placebo pretreatment. Fifteen minutes later, all animals received 103 mg/kg intraperitoneal cocaine. Overall mortality was 11% for olanzapine-treated animals and 45% for placebo. Olanzapine also appeared to alter the characteristics of seizures due to cocaine. In this model of acute cocaine toxicity, olanzapine pretreatment attenuated acute cocaine toxicity. Olanzapine should be evaluated further as a potential treatment for acute cocaine poisoning.

Plasminogen activator inhibitor type 1 gene is located at region q21. 3-q22 of chromosome 7 and genetically linked with cystic fibrosis

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

Klinger, K.W.; Winqvist, R.; Riccio, A.

1987-12-01

The regional chromosomal location of the human gene for plasminogen activator inhibitor type 1 (PAI1) was determined by three independent methods of gene mapping. PAI1 was localized first to 7cen-q32 and then to 7q21.3-q22 by Southern blot hybridization analysis of a panel of human and mouse somatic cell hybrids with a PAI1 cDNA probe and in situ hybridization, respectively. The authors frequent HindIII restriction fragment length polymorphism (RFLP) of the PAI1 gene with an information content of 0.369. In family studies using this polymorphism, genetic linkage was found between PAI1 and the loci for erythropoietin (EPO), paraoxonase (PON), the metmore » protooncogene (MET), and cystic fibrosis (CF), all previously assigned to the middle part of the long arm of chromosome 7. The linkage with EPO was closest with an estimated genetic distance of 3 centimorgans, whereas that to CF was 20 centimorgans. A three-point genetic linkage analysis and data from previous studies showed that the most likely order of these loci is EPO, PAI1, PON, (MET, CF), with PAI1 being located centromeric to CF. The PAI1 RFLP may prove to be valuable in ordering genetic markers in the CF-linkage group and may also be valuable in genetic analysis of plasminogen activation-related diseases, such as certain thromboembolic disorders and cancer.« less

In situ measurement of airway surface liquid [K+] using a ratioable K+-sensitive fluorescent dye.

PubMed

Namkung, Wan; Song, Yuanlin; Mills, Aaron D; Padmawar, Prashant; Finkbeiner, Walter E; Verkman, A S

2009-06-05

The airway surface liquid (ASL) is the thin fluid layer lining airway surface epithelial cells, whose volume and composition are tightly regulated and may be abnormal in cystic fibrosis (CF). We synthesized a two-color fluorescent dextran to measure ASL [K(+)], TAC-Lime-dextran-TMR, consisting of a green-fluorescing triazacryptand K(+) ionophore-Bodipy conjugate, coupled to dextran, together with a red fluorescing tetramethylrhodamine reference chromophore. TAC-Lime-dextran-TMR fluorescence was K(+)-selective, increasing >4-fold with increasing [K(+)] from 0 to 40 mm. In well differentiated human airway epithelial cells, ASL [K(+)] was 20.8 +/- 0.3 mm and decreased by inhibition of the Na(+)/K(+) pump (ouabain), ENaC (amiloride), CF transmembrane conductance regulator (CFTR(inh)-172), or K(+) channels (TEA or XE991). ASL [K(+)] was increased by forskolin but not affected by Na(+)/K(+)/2Cl(-) cotransporter inhibition (bumetanide). Functional and expression studies indicated the involvement of [K(+)] channels KCNQ1, KCNQ3, and KCNQ5 as determinants of ASL [K(+)]. [K(+)] in CF cultures was similar to that in non-CF cultures, suggesting that abnormal ASL [K(+)] is not a factor in CF lung disease. In intact airways, ASL [K(+)] was also well above extracellular [K(+)]: 22 +/- 1 mm in pig trachea ex vivo and 16 +/- 1 mm in mouse trachea in vivo. Our results provide the first noninvasive measurements of [K(+)] in the ASL and indicate the involvement of apical and basolateral membrane ion transporters in maintaining a high ASL [K(+)].

The porcine lung as a potential model for cystic fibrosis

PubMed Central

Rogers, Christopher S.; Abraham, William M.; Brogden, Kim A.; Engelhardt, John F.; Fisher, John T.; McCray, Paul B.; McLennan, Geoffrey; Meyerholz, David K.; Namati, Eman; Ostedgaard, Lynda S.; Prather, Randall S.; Sabater, Juan R.; Stoltz, David Anthony; Zabner, Joseph; Welsh, Michael J.

2008-01-01

Airway disease currently causes most of the morbidity and mortality in patients with cystic fibrosis (CF). However, understanding the pathogenesis of CF lung disease and developing novel therapeutic strategies have been hampered by the limitations of current models. Although the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) has been targeted in mice, CF mice fail to develop lung or pancreatic disease like that in humans. In many respects, the anatomy, biochemistry, physiology, size, and genetics of pigs resemble those of humans. Thus pigs with a targeted CFTR gene might provide a good model for CF. Here, we review aspects of porcine airways and lung that are relevant to CF. PMID:18487356

Targeting the Intracellular Environment in Cystic Fibrosis: Restoring Autophagy as a Novel Strategy to Circumvent the CFTR Defect

PubMed Central

Villella, Valeria Rachela; Esposito, Speranza; Bruscia, Emanuela M.; Maiuri, Maria Chiara; Raia, Valeria; Kroemer, Guido; Maiuri, Luigi

2013-01-01

Cystic fibrosis (CF) patients harboring the most common deletion mutation of the CF transmembrane conductance regulator (CFTR), F508del, are poor responders to potentiators of CFTR channel activity which can be used to treat a small subset of CF patients who genetically carry plasma membrane (PM)-resident CFTR mutants. The misfolded F508del-CFTR protein is unstable in the PM even if rescued by pharmacological agents that prevent its intracellular retention and degradation. CF is a conformational disease in which defective CFTR induces an impressive derangement of general proteostasis resulting from disabled autophagy. In this review, we discuss how rescuing Beclin 1 (BECN1), a major player of autophagosome formation, either by means of direct gene transfer or indirectly by administration of proteostasis regulators, could stabilize F508del-CFTR at the PM. We focus on the relationship between the improvement of peripheral proteostasis and CFTR PM stability in F508del-CFTR homozygous bronchial epithelia or mouse lungs. Moreover, this article reviews recent pre-clinical evidence indicating that targeting the intracellular environment surrounding the misfolded mutant CFTR instead of protein itself could constitute an attractive therapeutic option to sensitize patients carrying the F508del-CFTR mutation to the beneficial action of CFTR potentiators on lung inflammation. PMID:23346057

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.

Stem cell-derived organoids to model gastrointestinal facets of cystic fibrosis

PubMed Central

Hohwieler, Meike; Perkhofer, Lukas; Liebau, Stefan; Seufferlein, Thomas; Müller, Martin

2016-01-01

Cystic fibrosis (CF) is one of the most frequently occurring inherited human diseases caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) which lead to ample defects in anion transport and epithelial fluid secretion. Existing models lack both access to early stages of CF development and a coeval focus on the gastrointestinal CF phenotypes, which become increasingly important due increased life span of the affected individuals. Here, we provide a comprehensive overview of gastrointestinal facets of CF and the opportunity to model these in various systems in an attempt to understand and treat CF. A particular focus is given on forward-leading organoid cultures, which may circumvent current limitations of existing models and thereby provide a platform for drug testing and understanding of disease pathophysiology in gastrointestinal organs. PMID:28815024

75 FR 46868 - Airworthiness Directives; The Boeing Company Model 747 Airplanes and Model 767 Airplanes Equipped...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-04

... crystal accretion. However, at this time, we do not agree to pursue research to develop an ice detector... significantly different type-design booster from that of the GE Model CF6-80C2 series engines (GE Model CF6-80A... events recorded on GE Model CF6-80A series engines. While this engine has a similar compressor design...

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.

Rating knowledge sharing in cross-domain collaborative filtering.

PubMed

Li, Bin; Zhu, Xingquan; Li, Ruijiang; Zhang, Chengqi

2015-05-01

Cross-domain collaborative filtering (CF) aims to share common rating knowledge across multiple related CF domains to boost the CF performance. In this paper, we view CF domains as a 2-D site-time coordinate system, on which multiple related domains, such as similar recommender sites or successive time-slices, can share group-level rating patterns. We propose a unified framework for cross-domain CF over the site-time coordinate system by sharing group-level rating patterns and imposing user/item dependence across domains. A generative model, say ratings over site-time (ROST), which can generate and predict ratings for multiple related CF domains, is developed as the basic model for the framework. We further introduce cross-domain user/item dependence into ROST and extend it to two real-world cross-domain CF scenarios: 1) ROST (sites) for alleviating rating sparsity in the target domain, where multiple similar sites are viewed as related CF domains and some items in the target domain depend on their correspondences in the related ones; and 2) ROST (time) for modeling user-interest drift over time, where a series of time-slices are viewed as related CF domains and a user at current time-slice depends on herself in the previous time-slice. All these ROST models are instances of the proposed unified framework. The experimental results show that ROST (sites) can effectively alleviate the sparsity problem to improve rating prediction performance and ROST (time) can clearly track and visualize user-interest drift over time.

Cystic Fibrosis Transmembrane Conductance Regulator Regulates Epithelial Cell Response to Aspergillus and Resultant Pulmonary Inflammation

PubMed Central

Chaudhary, Neelkamal; Datta, Kausik; Askin, Frederic B.; Staab, Janet F.

2012-01-01

Rationale: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) alter epithelial cell (EC) interactions with multiple microbes, such that dysregulated inflammation and injury occur with airway colonization in people with cystic fibrosis (CF). Aspergillus fumigatus frequently colonizes CF airways, but it has been assumed to be an innocent saprophyte; its potential role as a cause of lung disease is controversial. Objectives: To study the interactions between Aspergillus and EC, and the role of the fungus in evoking inflammatory responses. Methods: A. fumigatus expressing green fluorescent protein was developed for in vitro and in vivo models, which used cell lines and mouse tracheal EC. Measurements and Main Results: Fungal spores (conidia) are rapidly ingested by ECs derived from bronchial cell lines and murine tracheas, supporting a role for EC in early airway clearance. Bronchial ECs harboring CFTR mutations (ΔF508) or deletion demonstrate impaired uptake and killing of conidia, and ECs with CFTR mutation undergo more conidial-induced apoptosis. Germinated (hyphal) forms of the fungus evoke secretion of inflammatory mediators, with CFTR mutation resulting in increased airway levels of macrophage inflammatory protein 2 and KC, and higher lung monocyte chemotactic protein-1. After A. fumigatus inhalation, CFTR−/− mice develop exaggerated lymphocytic inflammation, mucin accumulation, and lung injury. Conclusions: Data demonstrate a critical role for CFTR in mediating EC responses to A. fumigatus. Results suggest that the fungus elicits aberrant pulmonary inflammation in the setting of CFTR mutation, supporting the potential role of antifungals to halt progressive CF lung disease. PMID:22135344

Nebulized hyaluronan ameliorates lung inflammation in cystic fibrosis mice.

PubMed

Gavina, Manuela; Luciani, Alessandro; Villella, Valeria R; Esposito, Speranza; Ferrari, Eleonora; Bressani, Ilaria; Casale, Alida; Bruscia, Emanuela M; Maiuri, Luigi; Raia, Valeria

2013-08-01

Chronic lung inflammation with increased susceptibility to bacterial infections cause much of the morbidity and mortality in patients with cystic fibrosis (CF), the most common severe, autosomal recessively inherited disease in the Caucasian population. Exogenous inhaled hyaluronan (HA) can exert a protective effect against injury and beneficial effects of HA have been shown in experimental models of chronic respiratory diseases. Our objective was to examine whether exogenous administration of nebulized HA might interfere with lung inflammation in CF. F508del homozygous mice (Cftr(F508del) ) and transgenic mice overexpressing the ENaC channel β-subunit (Scnn1b-Tg) were treated with nebulized HA (0.5 mg/mouse/day for 7 days). Tumor necrosis factor-alpha (TNFα), macrophage inflammatory protein-2 (MIP-2), myeloperoxidase (MPO) levels, and macrophage infiltration were assessed on lung tissues. IB3-1 and CFBE41o-epithelial cell lines were cultured with HA (24 hr, 100 µg/ml) and Reactive Oxygen Species (ROS), Tissue Transglutaminase (TG2) SUMOylation and Peroxisome Proliferator Activated Receptor gamma (PPARγ) and phospho-p42/p44 levels were measured by dichlorodihydrofluorescein assay, or fluorescence resonance energy transfer (FRET) microscopy or immunoblots. Nebulized HA reduced TNFα expression (P < 0.005); TNFα, MIP-2, and MPO protein levels (P < 0.05); MPO activity (P < 0.05); and CD68+ cells counts (P < 0.005) in lung tissues of Cftr(F508del) and Scnn1b-Tg mice, compared with saline-treated mice. HA reduced ROS, TG2 SUMOylation, TG2 activity, phospho-p42-44, and increased PPARγ protein in both IB3-1 and CFBE41o cells (P < 0.05). Nebulized HA is effective in controlling inflammation in vivo in mice CF airways and in vitro in human airway epithelial cells. We provide the proof of concept for the use of inhaled HA as a potential anti-inflammatory drug in CF therapy. Copyright © 2012 Wiley Periodicals, Inc.

Intercomparison between CMIP5 model and MODIS satellite-retrieved data of aerosol optical depth, cloud fraction, and cloud-aerosol interactions

NASA Astrophysics Data System (ADS)

Sockol, Alyssa; Small Griswold, Jennifer D.

2017-08-01

Aerosols are a critical component of the Earth's atmosphere and can affect the climate of the Earth through their interactions with solar radiation and clouds. Cloud fraction (CF) and aerosol optical depth (AOD) at 550 nm from the Moderate Resolution Imaging Spectroradiometer (MODIS) are used with analogous cloud and aerosol properties from Historical Phase 5 of the Coupled Model Intercomparison Project (CMIP5) model runs that explicitly include anthropogenic aerosols and parameterized cloud-aerosol interactions. The models underestimate AOD by approximately 15% and underestimate CF by approximately 10% overall on a global scale. A regional analysis is then used to evaluate model performance in two regions with known biomass burning activity and absorbing aerosol (South America (SAM) and South Africa (SAF)). In SAM, the models overestimate AOD by 4.8% and underestimate CF by 14%. In SAF, the models underestimate AOD by 35% and overestimate CF by 13.4%. Average annual cycles show that the monthly timing of AOD peaks closely match satellite data in both SAM and SAF for all except the Community Atmosphere Model 5 and Geophysical Fluid Dynamics Laboratory (GFDL) models. Monthly timing of CF peaks closely match for all models (except GFDL) for SAM and SAF. Sorting monthly averaged 2° × 2.5° model or MODIS CF as a function of AOD does not result in the previously observed "boomerang"-shaped CF versus AOD relationship characteristic of regions with absorbing aerosols from biomass burning. Cloud-aerosol interactions, as observed using daily (or higher) temporal resolution data, are not reproducible at the spatial or temporal resolution provided by the CMIP5 models.

Proposal of diagnostic process model for computer based diagnosis.

PubMed

Matsumura, Yasushi; Takeda, Toshihiro; Manabe, Shiro; Saito, Hirokazu; Teramoto, Kei; Kuwata, Shigeki; Mihara, Naoki

2012-01-01

We aim at making a diagnosis support system that can be put to practical use. We proposed a diagnostic process model based on simple knowledge which can be gleaned from textbooks. We defined clinical finding (CF) as a general concept for patient's symptom or findings etc., whose value is expressed by Boolean. We call the combination of several CFs a "CF pattern", and a set of CF patterns with concomitant diseases "case base". We consider diagnosis as a process of searching an instance from the case base whose CF pattern is concomitant with that of a patient. The diseases which have the same CF pattern are candidates for diagnosis. Then we select a CF which is present in part of the candidates and check whether it is present or absent in the patient in order to narrow down the candidates. Because the case base does not exist in reality, the probability of CF pattern is calculated by the product of CF occurrence rate assuming that occurrence of CF is independent. Therefore the knowledge required for diagnosis is frequency of disease under sex and age group and CF-disease relation (CF and its occurrence rate in the disease). By processing these two types of knowledge, diagnosis can be made.

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.

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.

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

Homogentisate 1-2-Dioxygenase Downregulation in the Chronic Persistence of Pseudomonas aeruginosa Australian Epidemic Strain-1 in the CF Lung

PubMed Central

Harmer, Christopher J.; Wynn, Matthew; Pinto, Rachel; Cordwell, Stuart; Rose, Barbara R.; Harbour, Colin; Triccas, James A.; Manos, Jim

2015-01-01

Some Pseudomonas aeruginosa strains including Australian Epidemic Strain-1 (AES-1 or AUS-01) cause persistent chronic infection in cystic fibrosis (CF) patients, with greater morbidity and mortality. Factors conferring persistence are largely unknown. Previously we analysed the transcriptomes of AES-1 grown in Luria broth, nematode growth medium for Caenorhabditis elegans assay (both aerobic) and artificial sputum medium (mainly hypoxic). Transcriptional comparisons included chronic AES-1 strains against PAO1 and acute AES-1 (AES-1R) against its chronic isogen (AES-1M), isolated 10.5 years apart from a CF patient and not eradicated in the meantime. Prominent amongst genes downregulated in AES-1M in all comparisons was homogentisate-1-2-dioxygenase (hmgA); an oxygen-dependent gene known to be mutationally deactivated in many chronic infection strains of P. aeruginosa. To investigate if hmgA downregulation and deactivation gave similar virulence persistence profiles, a hmgA mutant made in UCBPP-PA14 utilising RedS-recombinase and AES-1M were assessed in the C. elegans virulence assay, and the C57BL/6 mouse for pulmonary colonisation and TNF-α response. In C. elegans, hmgA deactivation resulted in significantly increased PA14 virulence while hmgA downregulation reduced AES-1M virulence. AES-1M was significantly more persistent in mouse lung and showed a significant increase in TNF-α (p<0.0001), sustained even with no detectable bacteria. PA14ΔhmgA did not show increased TNF-α. This study suggests that hmgA may have a role in P. aeruginosa persistence in chronic infection and the results provide a starting point for clarifying the role of hmgA in chronic AES-1. PMID:26252386

Evaluation of cloud fraction and its radiative effect simulated by IPCC AR4 global models against ARM surface observations

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

Qian, Yun; Long, Charles N.; Wang, Hailong

2012-02-17

Cloud Fraction (CF) is the dominant modulator of radiative fluxes. In this study, we evaluate CF simulations in the IPCC AR4 GCMs against ARM ground measurements, with a focus on the vertical structure, total amount of cloud and its effect on cloud shortwave transmissivity, for both inter-model deviation and model-measurement discrepancy. Our intercomparisons of three CF or sky-cover related dataset reveal that the relative differences are usually less than 10% (5%) for multi-year monthly (annual) mean values, while daily differences are quite significant. The results also show that the model-observation and the inter-model deviations have a similar magnitude for themore » total CF (TCF) and the normalized cloud effect, and they are twice as large as the surface downward solar radiation and cloud transmissivity. This implies that the other cloud properties, such as cloud optical depth and height, have a similar magnitude of disparity to TCF among the GCMs, and suggests that a better agreement among the GCMs in solar radiative fluxes could be the result of compensating errors in either cloud vertical structure, cloud optical depth or cloud fraction. Similar deviation pattern between inter-model and model-measurement suggests that the climate models tend to generate larger bias against observations for those variables with larger inter-model deviation. The simulated TCF from IPCC AR4 GCMs are very scattered through all seasons over three ARM sites: Southern Great Plains (SGP), Manus, Papua New Guinea and North Slope of Alaska (NSA). The GCMs perform better at SGP than at Manus and NSA in simulating the seasonal variation and probability distribution of TCF; however, the TCF in these models is remarkably underpredicted and cloud transmissivity is less susceptible to the change of TCF than the observed at SGP. Much larger inter-model deviation and model bias are found over NSA than the other sites in estimating the TCF, cloud transmissivity and cloud-radiation interaction, suggesting that the Arctic region continues to challenge cloud simulations in climate models. Most of the GCMs tend to underpredict CF and fail to capture the seasonal variation of CF at middle and low levels in the tropics. The high altitude CF is much larger in the GCMs than the observation and the inter-model variability of CF also reaches maximum at high levels in the tropics. Most of the GCMs tend to underpredict CF by 50-150% relative to the measurement average at low and middle levels over SGP. While the GCMs generally capture the maximum CF in the boundary layer and vertical variability, the inter-model deviation is largest near surface over the Arctic. The internal variability of CF simulated in ensemble runs with the same model is very minimal.« less

Cystic Fibrosis and the Nervous System.

PubMed

Reznikov, Leah R

2017-05-01

Cystic fibrosis (CF) is a life-shortening autosomal recessive disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an anion channel that conducts bicarbonate and chloride across cell membranes. Although defective anion transport across epithelial cells is accepted as the basic defect in CF, many of the features observed in people with CF and organs affected by CF are modulated by the nervous system. This is of interest because CFTR expression has been reported in both the peripheral and central nervous systems, and it is well known that the transport of anions, such as chloride, greatly modulates neuronal excitability. Thus it is predicted that in CF, lack of CFTR in the nervous system affects neuronal function. Consistent with this prediction, several nervous system abnormalities and nervous system disorders have been described in people with CF and in animal models of CF. The goal of this special feature article is to highlight the expression and function of CFTR in the nervous system. Special emphasis is placed on nervous system abnormalities described in people with CF and in animal models of CF. Finally, features of CF that may be modulated by or attributed to faulty nervous system function are discussed. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Shock wave and modeling study of the thermal decomposition reactions of pentafluoroethane and 2-H-heptafluoropropane.

PubMed

Cobos, C J; Sölter, L; Tellbach, E; Troe, J

2014-06-07

The thermal decomposition reactions of CF3CF2H and CF3CFHCF3 have been studied in shock waves by monitoring the appearance of CF2 radicals. Temperatures in the range 1400-2000 K and Ar bath gas concentrations in the range (2-10) × 10(-5) mol cm(-3) were employed. It is shown that the reactions are initiated by C-C bond fission and not by HF elimination. Differing conclusions in the literature about the primary decomposition products, such as deduced from experiments at very low pressures, are attributed to unimolecular falloff effects. By increasing the initial reactant concentrations in Ar from 60 to 1000 ppm, a retardation of CF2 formation was observed while the final CF2 yields remained close to two CF2 per C2F5H or three CF2 per C3F7H decomposed. This is explained by secondary bimolecular reactions which lead to comparably stable transient species like CF3H, releasing CF2 at a slower rate. Quantum-chemical calculations and kinetic modeling help to identify the reaction pathways and provide estimates of rate constants for a series of primary and secondary reactions in the decomposition mechanism.

Genetic variation and effects of candidate-gene polymorphisms on coagulation properties, curd firmness modeling and acidity in milk from Brown Swiss cows.

PubMed

Cecchinato, A; Chessa, S; Ribeca, C; Cipolat-Gotet, C; Bobbo, T; Casellas, J; Bittante, G

2015-07-01

The aims of this study were to estimate the genetic variation of traditional milk coagulation properties (MCPs), milk acidity, curd firmness (CF) modeled on time t (CF(t) ; comprising: RCT(eq), rennet coagulation time estimated from the equation; CF(P), the asymptotic potential curd firmness; k(CF), the curd firming instant rate constant; and k(SR), the syneresis instant rate constant) and maximum CF traits (MCF; comprising CF(max), the maximum CF value; and tmax, the time of attainment). Furthermore, we investigated 96 single nucleotide polymorphisms (SNPs) from 54 candidate genes, testing their associations with the above-listed traits. Milk and blood samples were collected from 1271 cows (each sampled once) from 85 herds. Genotyping was performed using a custom Illumina VeraCode GoldenGate approach. A Bayesian linear animal model (including the effects of herd, days in milk, parity and additive polygenic effects) was used to estimate the genetic parameters of the studied traits. The same model with the addition of the SNP genotype effect was used for our association analysis. The heritability estimates of CF t and the MCF traits (RCT(eq)=0.258; k(CF)=0.230; CF(max)=0.191; t(max)=0.278) were similar to those obtained using traditional MCPs (0.187 to 0.267), except for the lower estimates for CF(P) (0.064) and k(SR) (0.077). A total of 13 of the 51 tested SNPs had relevant additive effects on at least one trait. We observed associations between MCPs and SNPs in the genes encoding ATP-binding cassette sub-family G member 2 (ABCG2), chemokine ligand 2 (CCL2), growth hormone 1 (GH1), prolactin (PRL) and toll-like receptor 2 (TLR2). Whereas, CF(t) and the MCF traits were associated with polymorphisms in the α-s1-casein (CSN1S1), β-casein (CSN2), GH1, oxidized low-density lipoprotein receptor 1 (OLR1), phospholipase C β1 (PLCB1), PRL and signal transducer and activator of transcription 5A (STAT5A) genes.

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

Population-level genomics identifies the emergence and global spread of a human transmissible multidrug-resistant nontuberculous mycobacterium

PubMed Central

Rodriguez-Rincon, Daniela; Everall, Isobel; Brown, Karen P; Moreno, Pablo; Verma, Deepshikha; Hill, Emily; Drijkoningen, Judith; Gilligan, Peter; Esther, Charles R; Noone, Peadar G; Giddings, Olivia; Bell, Scott C.; Thomson, Rachel; Wainwright, Claire E.; Coulter, Chris; Pandey, Sushil; Wood, Michelle E; Stockwell, Rebecca E; Ramsay, Kay A; Sherrard, Laura J; Kidd, Timothy J; Jabbour, Nassib; Johnson, Graham R; Knibbs, Luke D; Morawska, Lidia; Sly, Peter D; Jones, Andrew; Bilton, Diana; Laurenson, Ian; Ruddy, Michael; Bourke, Stephen; Bowler, Ian CJW; Chapman, Stephen J; Clayton, Andrew; Cullen, Mairi; Daniels, Thomas; Dempsey, Owen; Denton, Miles; Desai, Maya; Drew, Richard J; Edenborough, Frank; Evans, Jason; Folb, Jonathan; Humphrey, Helen; Isalska, Barbara; Jensen-Fangel, Søren; Jönsson, Bodil; Jones, Andrew M.; Katzenstein, Terese L; Lillebaek, Troels; MacGregor, Gordon; Mayell, Sarah; Millar, Michael; Modha, Deborah; Nash, Edward F; O’Brien, Christopher; O’Brien, Deirdre; Ohri, Chandra; Pao, Caroline S; Peckham, Daniel; Perrin, Felicity; Perry, Audrey; Pressler, Tania; Prtak, Laura; Qvist, Tavs; Robb, Ali; Rodgers, Helen; Schaffer, Kirsten; Shafi, Nadia; van Ingen, Jakko; Walshaw, Martin; Watson, Danie; West, Noreen; Whitehouse, Joanna; Haworth, Charles S; Harris, Simon R; Ordway, Diane; Parkhill, Julian; Floto, R. Andres

2016-01-01

Lung infections with Mycobacterium abscessus, a species of multidrug resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF) where they accelerate inflammatory lung damage leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge. PMID:27846606

[Virulence of Sporothrix globosa in murine models].

PubMed

Cruz Choappa, Rodrigo; Pérez Gaete, Salomón; Rodríguez Badilla, Valentina; Vieille Oyarzo, Peggy; Opazo Sanchez, Héctor

The sporothricosis disease is an infection caused by species included in Sporothrix schenkii complex. Verify the virulence of a strain of S. globosa using two different concentrations of inoculum by intraperitoneally and subcutaneously, into a mouse model. Nonrandomized pilot study, in murine inoculated with a strain of S. globosa (CBS 14.076M) by intraperitoneally and subcutaneously with inoculum concentrations of 0.5 and 4 McFarland. For this purpose 18 rodents CF-1 (ISP, Santiago, Chile) were used. The studied strain did not induce illness or injury on animals, they all survived and neither the tissue culture nor the histopathological analysis showed fungal growth or suggestive infection by organ abnormalities. The S. globosa strain did not present any virulence enough to cause disease at 0.5 and 4.0 McFarland concentration inoculum when inoculated in both intraperitoneally and subcutaneously, in murine models. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Removal of ammonium and heavy metals by cost-effective zeolite synthesized from waste quartz sand and calcium fluoride sludge.

PubMed

Zhang, Qian; Lin, Bing; Hong, Junming; Chang, Chang-Tang

2017-02-01

This study focuses on the effectiveness of zeolite (10% CF-Z [0.5]) hydrothermally synthesized from waste quartz sand and calcium fluoride (CF) for ammonium ion and heavy metal removal. Zeolite was characterized through powder X-ray diffraction, Fourier-transform infrared spectroscopy, micromeritics N 2 adsorption/desorption analysis, and field emission scanning electron microscopy. The effects of CF addition, Si/Al ratio, initial ammonium concentration, solution pH, and temperature on the adsorption of ammonium on 10% CF-Z (0.5) were further examined. Results showed that 10% CF-Z (0.5) was a single-phase zeolite A with cubic-shaped crystals and 10% CF-Z (0.5) efficiently adsorbs ammonium and heavy metals. For instance, 91% ammonium (10 mg L -1 ) and 93% lead (10 mg L -1 ) are removed. The adsorption isotherm, kinetics, and thermodynamics of ammonium adsorption on 10% CF-Z (0.5) were also theoretically analyzed. The adsorption isotherm of ammonium and lead on 10% CF-Z (0.5) in single systems indicated that Freundlich model provides the best fit for the equilibrium data, whereas pseudo-second-order model best describes the adsorption kinetics. The adsorption degree of ions on 10% CF-Z (0.5) in mixed systems exhibits the following pattern: lead > ammonium > cadmium > chromium.

Improving Representation of Tropical Cloud Overlap in GCMs Based on Cloud-Resolving Model Data

NASA Astrophysics Data System (ADS)

Jing, Xianwen; Zhang, Hua; Satoh, Masaki; Zhao, Shuyun

2018-04-01

The decorrelation length ( L cf) has been widely used to describe the behavior of vertical overlap of clouds in general circulation models (GCMs); however, it has been a challenge to associate L cf with the large-scale meteorological conditions during cloud evolution. This study explored the relationship between L cf and the strength of atmospheric convection in the tropics based on output from a global cloud-resolving model. L cf tends to increase with vertical velocity in the mid-troposphere ( w 500) at locations of ascent, but shows little or no dependency on w 500 at locations of descent. A representation of L cf as a function of vertical velocity is obtained, with a linear regression in ascending regions and a constant value in descending regions. This simple and dynamic-related representation of L cf leads to a significant improvement in simulation of both cloud cover and radiation fields compared with traditional overlap treatments. This work presents a physically justifiable approach to depicting cloud overlap in the tropics in GCMs.

Removal Rate of Organic Matter Using Natural Cellulose via Adsorption Isotherm and Kinetic Studies.

PubMed

Din, Mohd Fadhil Md; Ponraj, Mohanadoss; Low, Wen-Pei; Fulazzaky, Mohamad Ali; Iwao, Kenzo; Songip, Ahmad Rahman; Chelliapan, Shreeshivadasan; Ismail, Zulhilmi; Jamal, Mohamad Hidayat

2016-02-01

In this study, the removal of natural organic matter (NOM) using coconut fiber (CF) and palm oil fiber (POF) was investigated. Preliminary analysis was performed using a jar test for the selection of optimal medium before the fabricated column model experiment. The equilibrium studies on isotherms and kinetic models for NOM adsorption were analyzed using linearized correlation coefficient. Results showed that the equilibrium data were fitted to Langmuir isotherm model for both CF and POF. The most suitable adsorption model was the pseudo-first-order kinetic model for POF and pseudo-second-order kinetic model for CF. The adsorption capacities achieved by the CF and POF were 15.67 and 30.8 mg/g respectively. Based on this investigation, it can be concluded that the POF is the most suitable material for the removal of NOM in semi polluted river water.

Chronobiological factors for compassion satisfaction and fatigue among ambulatory oncology caregivers.

PubMed

Bellicoso, Daniela; Trudeau, Maureen; Fitch, Margaret I; Ralph, Martin R

2017-01-01

Primary caregivers for victims of chronic illness and or trauma experience both positive and negative emotional consequences. These are broadly classified as compassion satisfaction (CS) and compassion fatigue (CF). Because one of the components of CF, burnout, varies with chronotype and sleep quality, we assessed the influence of chronobiological features on the broader constructs of CS and CF. Responses from primary ambulatory care oncology staff working dayshifts were assessed for potential relationships of chronotype and sleep quality with CS and CF using the professional quality of life scale. These were analyzed further in a multivariate model that included personality and job satisfaction as cofactors. We found that sleep quality was a key contributor to CS development and CF reduction. Morningness was positively linked to CS, but the univariate association was masked in the multivariate model. Job satisfaction (contingent rewards, nature of work and operating procedures) heavily influenced CS and CF development. Agreeableness and openness showed positive correlations with CS and negative with burnout, while emotional stability was linked to reduced CF. While job satisfaction and personality predictably played roles in the development of CS and CF, sleep quality and chronotype contributed significantly to benefits and negative consequences of providing care.

CFTR, Mucins, and Mucus Obstruction in Cystic Fibrosis

PubMed Central

Kreda, Silvia M.; Davis, C. William; Rose, Mary Callaghan

2012-01-01

Mucus pathology in cystic fibrosis (CF) has been known for as long as the disease has been recognized and is sometimes called mucoviscidosis. The disease is marked by mucus hyperproduction and plugging in many organs, which are usually most fatal in the airways of CF patients, once the problem of meconium ileus at birth is resolved. After the CF gene, CFTR, was cloned and its protein product identified as a cAMP-regulated Cl− channel, causal mechanisms underlying the strong mucus phenotype of the disease became obscure. Here we focus on mucin genes and polymeric mucin glycoproteins, examining their regulation and potential relationships to a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR). Detailed examination of CFTR expression in organs and different cell types indicates that changes in CFTR expression do not always correlate with the severity of CF disease or mucus accumulation. Thus, the mucus hyperproduction that typifies CF does not appear to be a direct cause of a defective CFTR but, rather, to be a downstream consequence. In organs like the lung, up-regulation of mucin gene expression by inflammation results from chronic infection; however, in other instances and organs, the inflammation may have a non-infectious origin. The mucus plugging phenotype of the β-subunit of the epithelial Na+ channel (βENaC)-overexpressing mouse is proving to be an archetypal example of this kind of inflammation, with a dehydrated airway surface/concentrated mucus gel apparently providing the inflammatory stimulus. Data indicate that the luminal HCO3 − deficiency recently described for CF epithelia may also provide such a stimulus, perhaps by causing a mal-maturation of mucins as they are released onto luminal surfaces. In any event, the path between CFTR dysfunction and mucus hyperproduction has proven tortuous, and its unraveling continues to offer its own twists and turns, along with fascinating glimpses into biology. PMID:22951447

Commercial complementary food consumption is prospectively associated with added sugar intake in childhood.

PubMed

Foterek, Kristina; Buyken, Anette E; Bolzenius, Katja; Hilbig, Annett; Nöthlings, Ute; Alexy, Ute

2016-06-01

Given that commercial complementary food (CF) can contain high levels of added sugar, a high consumption may predispose to a preference for sweet taste later in life. This study examined cross-sectional associations between commercial CF consumption and added sugar intake in infancy as well as its prospective relation to added sugar intake in pre-school and primary-school age children. In all, 288 children of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study with 3-d weighed dietary records at 0·5 and 0·75 (infancy), 3 and 4 (pre-school age) and 6 and 7 years of age (primary-school age) were included in this analysis. Individual commercial CF consumption as percentage of total commercial CF (%cCF) was averaged at 0·5 and 0·75 years. Individual total added sugar intake (g/d, energy percentage/d) was averaged for all three age groups. Multivariable logistic and linear regression models were used to analyse associations between %cCF and added sugar intake. In infancy, a higher %cCF was associated with odds for high added sugar intake from CF and for high total added sugar intake (>75th percentile, P<0·033). Prospectively, a higher %cCF was related to higher added sugar intake in both pre-school (P<0·041) and primary-school age children (P<0·039), although these associations were attenuated in models adjusting for added sugar intake in infancy. A higher %cCF in infancy may predispose to higher added sugar intake in later childhood by virtue of its added sugar content. Therefore, offering home-made CF or carefully chosen commercial CF without added sugar might be one strategy to reduce sugar intake in infancy and later on.

Diagnosing cystic fibrosis in newborn screening in Poland - 15 years of experience.

PubMed

Sands, Dorota; Zybert, Katarzyna; Mierzejewska, Ewa; Ołtarzewski, Mariusz

2015-01-01

Early diagnosis of cystic fibrosis (CF) made by the introduction of CF NBS (Cystic Fibrosis Newborn Screening) provides the opportunity to undertake preventive measures and provide treatment before the development of irreversible changes in the respiratory tract and other complications. CF NBS was conducted as a pilot programme in four Polish districts in the period 1999-2003. In 2006 CF NBS started again and was gradually extended across the country. The aim of this study was to show the evolution of the Polish CF NBS strategies and assess the diagnostic consequences of this programme. The study involved children diagnosed and treated only in the IMiD Centre. The strategy in Polish CF NBS was modified over time. Firstly, the model IRT/IRT and IRT/IRT/DNA with one mutation was implemented, which was followed by IRT/DNA with a gradually expanding number of CFTR mutations (tab. I). Newborns with positive results of CF NBS were called to the CF IMiD Centre, and sweat tests were performed. The children diagnosed and children with mutations in both alleles of the CFTR gene even if at least one of them had undefined pathogenicity) were taken under IMiD Centre care. Sensitivity, specificity and positive predictive values during subsequent stages of CF NBS were calculated (tab. III). During the 1999-2003 pilot study 444 063 newborns underwent CF NBS and in 74 cases CF was diagnosed. 582 693 newborns were screened from September 2006 to December 2011 in four regions and 100 children were diagnosed with CF. The frequencies of CF in the Polish population in both screening periods were 1:5767 and 1:5712 respectively. Firstly, the IRT/IRT model was implemented, but the number of newborns called to the CF Centre was high - the PPV was 7.6%. In the next step CF NBS DNA analysis was used. Here sensitivity and specificity were high - nearly 100%. In the following years the number of mutations detected was expanded (including 16 most common ones in the Polish population). Due to the panel changes, the number of calls declined and the PPV (predictive positive value) improved (to 26.1%) after the application of expanded genetic analysis. Expanding the panel of mutations resulted in an increased number of carriers and observational subjects. IRT/DNA strategy with expanded DNA analysis provides the opportunity for earlier CF diagnosis even in children with normal sweat test values. However, this model caused frequent carrier detection and inconclusive diagnosis in comparison to IRT/IRT or IRT/IRT/DNA with a limited number of mutations. Further research and changes in Polish CF NBS are needed to increase the PPV, while preserving high sensitivity and specificity..

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

Inhibition of NFkappaB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation.

PubMed

Maitra, Rangan; Porter, Melissa A; Huang, Shan; Gilmour, Brian P

2009-05-13

Cystic Fibrosis (CF) is one of the most common autosomal genetic disorders in humans. This disease is caused by mutations within a single gene, coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The phenotypic hallmark of CF is chronic lung infection and associated inflammation from opportunistic microbes such as Pseudomonas aeruginosa (PA), Haemophilus influenzae, and Staphylococcus aureus. This eventually leads to deterioration of lung function and death in most CF patients. Unfortunately, there is no approved therapy for correcting the genetic defect causal to the disease. Hence, controlling inflammation and infection in CF patients are critical to disease management. Accordingly, anti-inflammatory agents and antibiotics are used to manage chronic inflammation and infection in CF patients. However, most of the anti-inflammatory agents in CF have severe limitations due to adverse side effects, and resistance to antibiotics is becoming an even more prominent problem. Thus, new agents that can be used to control chronic inflammation in CF are needed in the absence of a cure for the disease. Activation of the transcription factor NFkappaB through Toll-like receptors (TLR) following bacterial infection is principally involved in regulating lung inflammation in CF. NFkappaB regulates the transcription of several genes that are involved in inflammation, anti-apoptosis and anti-microbial activity, and hyper-activation of this transcription factor leads to a potent inflammatory response. Thus, NFkappaB is a potential anti-inflammatory drug target in CF. Screening of several compounds from natural sources in an in vitro model of CF-related inflammation wherein NFkappaB is activated by filtrates of a clinically isolated strain of PA (PAF) led us to Withaferin A (WFA), a steroidal lactone from the plant Withania Somnifera L. Dunal. Our data demonstrate that WFA blocks PAF-induced activation of NFkappaB as determined using reporter assays, IL-8 measurements and high-content fluorescent imaging of NFkappaB subunit p65 translocation. Since the airways of CF patients can be specifically targeted for delivery of therapeutics, we propose that WFA should be further studied as an anti-inflammatory agent in models of CF related inflammation mediated by NFkappaB.

Median regression spline modeling of longitudinal FEV1 measurements in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) patients.

PubMed

Conrad, Douglas J; Bailey, Barbara A; Hardie, Jon A; Bakke, Per S; Eagan, Tomas M L; Aarli, Bernt B

2017-01-01

Clinical phenotyping, therapeutic investigations as well as genomic, airway secretion metabolomic and metagenomic investigations can benefit from robust, nonlinear modeling of FEV1 in individual subjects. We demonstrate the utility of measuring FEV1 dynamics in representative cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) populations. Individual FEV1 data from CF and COPD subjects were modeled by estimating median regression splines and their predicted first and second derivatives. Classes were created from variables that capture the dynamics of these curves in both cohorts. Nine FEV1 dynamic variables were identified from the splines and their predicted derivatives in individuals with CF (n = 177) and COPD (n = 374). Three FEV1 dynamic classes (i.e. stable, intermediate and hypervariable) were generated and described using these variables from both cohorts. In the CF cohort, the FEV1 hypervariable class (HV) was associated with a clinically unstable, female-dominated phenotypes while stable FEV1 class (S) individuals were highly associated with the male-dominated milder clinical phenotype. In the COPD cohort, associations were found between the FEV1 dynamic classes, the COPD GOLD grades, with exacerbation frequency and symptoms. Nonlinear modeling of FEV1 with splines provides new insights and is useful in characterizing CF and COPD clinical phenotypes.

Efficient mouse airway transduction following recombination between AAV vectors carrying parts of a larger gene.

PubMed

Halbert, Christine L; Allen, James M; Miller, A Dusty

2002-07-01

The small packaging capacity of adeno-associated virus (AAV) vectors limits the utility of this promising vector system for transfer of large genes. We explored the possibility that larger genes could be reconstituted following homologous recombination between AAV vectors carrying overlapping gene fragments. An alkaline phosphatase (AP) gene was split between two such AAV vectors (rec vectors) and packaged using AAV2 or AAV6 capsid proteins. Rec vectors having either capsid protein recombined to express AP in cultured cells at about 1-2% of the rate observed for an intact vector. Surprisingly, the AAV6 rec vectors transduced lung cells in mice almost as efficiently as did an intact vector, with 10% of airway epithelial cells, the target for treatment of cystic fibrosis (CF), being positive. Thus AAV rec vectors may be useful for diseases such as CF that require transfer of large genes.

Biochemical and chemical characterization of trifluoromethylglyoxal bis(guanylhydrazone), a close analog of the antileukemic drug mitoguazone.

PubMed

Elo, H; Mutikainen, I

1988-01-01

In order to study the structure-activity relationships of bis(guanylhydrazone) type polyamine antimetabolites, trifluoromethylglyoxal bis(guanylhydrazone) (CF3-GBG), a close analog of the antileukemic drug methylglyoxal bis(guanylhydrazone) (mitoguazone, MGBG) was synthesized according to a novel modification of previous methods, yielding single crystals. Single-crystal X-ray crystallography revealed the presence of an isomer different from the one detected in the case of MGBG and all other bis(guanylhydrazones) so far studied. In contrast to MGBG, CF3-GBG was shown to be a very weak inhibitor of yeast adenosylmethionine decarboxylase, being thus devoid of value as a polyamine antimetabolite. In addition, the compound did not have antiproliferative activity against mouse L1210 leukemia cells in vitro. As long as analogous isomers of the two compounds are not available, no conclusions can be drawn about the reasons lying behind the drastical differences between their biological properties.

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

Effect of Manure vs. Fertilizer Inputs on Productivity of Forage Crop Models

PubMed Central

Annicchiarico, Giovanni; Caternolo, Giovanni; Rossi, Emanuela; Martiniello, Pasquale

2011-01-01

Manure produced by livestock activity is a dangerous product capable of causing serious environmental pollution. Agronomic management practices on the use of manure may transform the target from a waste to a resource product. Experiments performed on comparison of manure with standard chemical fertilizers (CF) were studied under a double cropping per year regime (alfalfa, model I; Italian ryegrass-corn, model II; barley-seed sorghum, model III; and horse-bean-silage sorghum, model IV). The total amount of manure applied in the annual forage crops of the model II, III and IV was 158, 140 and 80 m3 ha−1, respectively. The manure applied to soil by broadcast and injection procedure provides an amount of nitrogen equal to that supplied by CF. The effect of manure applications on animal feeding production and biochemical soil characteristics was related to the models. The weather condition and manures and CF showed small interaction among treatments. The number of MFU ha−1 of biomass crop gross product produced in autumn and spring sowing models under manure applications was 11,769, 20,525, 11,342, 21,397 in models I through IV, respectively. The reduction of MFU ha−1 under CF ranges from 10.7% to 13.2% those of the manure models. The effect of manure on organic carbon and total nitrogen of topsoil, compared to model I, stressed the parameters as CF whose amount was higher in models II and III than model IV. In term of percentage the organic carbon and total nitrogen of model I and treatment with manure was reduced by about 18.5 and 21.9% in model II and model III and 8.8 and 6.3% in model IV, respectively. Manure management may substitute CF without reducing gross production and sustainability of cropping systems, thus allowing the opportunity to recycle the waste product for animal forage feeding. PMID:21776208

Effect of manure vs. fertilizer inputs on productivity of forage crop models.

PubMed

Annicchiarico, Giovanni; Caternolo, Giovanni; Rossi, Emanuela; Martiniello, Pasquale

2011-06-01

Manure produced by livestock activity is a dangerous product capable of causing serious environmental pollution. Agronomic management practices on the use of manure may transform the target from a waste to a resource product. Experiments performed on comparison of manure with standard chemical fertilizers (CF) were studied under a double cropping per year regime (alfalfa, model I; Italian ryegrass-corn, model II; barley-seed sorghum, model III; and horse-bean-silage sorghum, model IV). The total amount of manure applied in the annual forage crops of the model II, III and IV was 158, 140 and 80 m3 ha(-1), respectively. The manure applied to soil by broadcast and injection procedure provides an amount of nitrogen equal to that supplied by CF. The effect of manure applications on animal feeding production and biochemical soil characteristics was related to the models. The weather condition and manures and CF showed small interaction among treatments. The number of MFU ha(-1) of biomass crop gross product produced in autumn and spring sowing models under manure applications was 11,769, 20,525, 11,342, 21,397 in models I through IV, respectively. The reduction of MFU ha(-1) under CF ranges from 10.7% to 13.2% those of the manure models. The effect of manure on organic carbon and total nitrogen of topsoil, compared to model I, stressed the parameters as CF whose amount was higher in models II and III than model IV. In term of percentage the organic carbon and total nitrogen of model I and treatment with manure was reduced by about 18.5 and 21.9% in model II and model III and 8.8 and 6.3% in model IV, respectively. Manure management may substitute CF without reducing gross production and sustainability of cropping systems, thus allowing the opportunity to recycle the waste product for animal forage feeding.

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.

An Integrated Loop Model of Corrective Feedback and Oral English Learning: A Case of International Students in the United States

ERIC Educational Resources Information Center

Lee, Eun Jeong

2017-01-01

The author in this study introduces an integrated corrective feedback (CF) loop to schematize the interplay between CF and independent practice in L2 oral English learning among advanced-level adult ESL students. The CF loop integrates insights from the Interaction, Output, and Noticing Hypotheses to show how CF can help or harm L2 learners'…

Abnormal endocrine pancreas function at birth in cystic fibrosis ferrets

PubMed Central

Olivier, Alicia K.; Yi, Yaling; Sun, Xingshen; Sui, Hongshu; Liang, Bo; Hu, Shanming; Xie, Weiliang; Fisher, John T.; Keiser, Nicholas W.; Lei, Diana; Zhou, Weihong; Yan, Ziying; Li, Guiying; Evans, Turan I.A.; Meyerholz, David K.; Wang, Kai; Stewart, Zoe A.; Norris, Andrew W.; Engelhardt, John F.

2012-01-01

Diabetes is a common comorbidity in cystic fibrosis (CF) that worsens prognosis. The lack of an animal model for CF-related diabetes (CFRD) has made it difficult to dissect how the onset of pancreatic pathology influences the emergence of CFRD. We evaluated the structure and function of the neonatal CF endocrine pancreas using a new CFTR-knockout ferret model. Although CF kits are born with only mild exocrine pancreas disease, progressive exocrine and endocrine pancreatic loss during the first months of life was associated with pancreatic inflammation, spontaneous hyperglycemia, and glucose intolerance. Interestingly, prior to major exocrine pancreas disease, CF kits demonstrated significant abnormalities in blood glucose and insulin regulation, including diminished first-phase and accentuated peak insulin secretion in response to glucose, elevated peak glucose levels following glucose challenge, and variably elevated insulin and C-peptide levels in the nonfasted state. Although there was no difference in lobular insulin and glucagon expression between genotypes at birth, significant alterations in the frequencies of small and large islets were observed. Newborn cultured CF islets demonstrated dysregulated glucose-dependent insulin secretion in comparison to controls, suggesting intrinsic abnormalities in CF islets. These findings demonstrate that early abnormalities exist in the regulation of insulin secretion by the CF endocrine pancreas. PMID:22996690

Rapid Diagnosis of Arbovirus and Arenavirus Infections by Immunofluorescence.

DTIC Science & Technology

1980-01-01

addition to Banzi virus in the blood of viremic mice, other viruses were tested with a view to correlate in an amplifying cell culture system the result of... Virus identification. Two viruses , F-41451 and Aus-CF 122, partially identified at the originating laboratories, were submitted to YARU for final...two ampules of the corresponding virus stocks and 6 x 0.5 ml of hyperimmune mouse serum were included In the shipment. The viruses and cells used and

Malabsorption Blood Test: Assessing Fat Absorption in Patients with Cystic Fibrosis and Pancreatic Insufficiency

PubMed Central

Mascarenhas, Maria R.; Mondick, John; Barrett, Jeffrey S.; Wilson, Martha; Stallings, Virginia A.; Schall, Joan I.

2015-01-01

The Malabsorption Blood Test (MBT), consisting of pentadecanoic acid (PA), a free fatty acid and triheptadecanoic acid (THA), a triglyceride that requires pancreatic lipase for absorption of the heptadecanoic acid (HA), was developed to assess fat malabsorption in patients with cystic fibrosis (CF) and pancreatic insufficiency (PI). The objective was to construct a population pharmacokinetic (PK) model to describe PA and HA disposition in healthy subjects and CF subjects. A model was simultaneously fit to PA and HA concentrations, consisting of one compartment disposition and a transit model to describe absorption. PA bioavailability estimates for CF subjects without pancreatic enzyme administration [1.07 (0.827,1.42)] and with enzymes [0.88 (0.72,1.09)] indicated PA absorption comparable to healthy subjects. HA bioavailability in CF without enzyme administration was 0.0292 (0.0192,0.0459), and with enzymes increased to 0.606 (0.482,0.823). In CF, compared to taking enzymes with the MBT, HA bioavailability was further decreased by factors of 0.829 (0.664,0.979) and 0.78 (0.491,1.13) with enzymes taken 30 and 60 minutes after MBT, respectively. The MBT detected differences in fat absorption in subjects with CF with and without enzyme administration and with changes in enzyme timing. Future studies will address application of the MBT in CF and other malabsorption diagnoses. PMID:25689042

Cortical connective field estimates from resting state fMRI activity.

PubMed

Gravel, Nicolás; Harvey, Ben; Nordhjem, Barbara; Haak, Koen V; Dumoulin, Serge O; Renken, Remco; Curčić-Blake, Branislava; Cornelissen, Frans W

2014-01-01

One way to study connectivity in visual cortical areas is by examining spontaneous neural activity. In the absence of visual input, such activity remains shaped by the underlying neural architecture and, presumably, may still reflect visuotopic organization. Here, we applied population connective field (CF) modeling to estimate the spatial profile of functional connectivity in the early visual cortex during resting state functional magnetic resonance imaging (RS-fMRI). This model-based analysis estimates the spatial integration between blood-oxygen level dependent (BOLD) signals in distinct cortical visual field maps using fMRI. Just as population receptive field (pRF) mapping predicts the collective neural activity in a voxel as a function of response selectivity to stimulus position in visual space, CF modeling predicts the activity of voxels in one visual area as a function of the aggregate activity in voxels in another visual area. In combination with pRF mapping, CF locations on the cortical surface can be interpreted in visual space, thus enabling reconstruction of visuotopic maps from resting state data. We demonstrate that V1 ➤ V2 and V1 ➤ V3 CF maps estimated from resting state fMRI data show visuotopic organization. Therefore, we conclude that-despite some variability in CF estimates between RS scans-neural properties such as CF maps and CF size can be derived from resting state data.

IFN-γ Stimulates Autophagy-Mediated Clearance of Burkholderia cenocepacia in Human Cystic Fibrosis Macrophages

PubMed Central

Assani, Kaivon; Tazi, Mia F.; Amer, Amal O.; Kopp, Benjamin T.

2014-01-01

Burkholderia cenocepacia is a virulent pathogen that causes significant morbidity and mortality in patients with cystic fibrosis (CF), survives intracellularly in macrophages, and uniquely causes systemic infections in CF. Autophagy is a physiologic process that involves engulfing non-functional organelles and proteins and delivering them for lysosomal degradation, but also plays a role in eliminating intracellular pathogens, including B. cenocepacia. Autophagy is defective in CF but can be stimulated in murine CF models leading to increased clearance of B. cenocepacia, but little is known about autophagy stimulation in human CF macrophages. IFN-γ activates macrophages and increases antigen presentation while also inducing autophagy in macrophages. We therefore, hypothesized that treatment with IFN-γ would increase autophagy and macrophage activation in patients with CF. Peripheral blood monocyte derived macrophages (MDMs) were obtained from CF and non-CF donors and subsequently infected with B. cenocepacia. Basal serum levels of IFN-γ were similar between CF and non-CF patients, however after B. cenocepacia infection there is deficient IFN-γ production in CF MDMs. IFN-γ treated CF MDMs demonstrate increased co-localization with the autophagy molecule p62, increased autophagosome formation, and increased trafficking to lysosomes compared to untreated CF MDMs. Electron microscopy confirmed IFN-γ promotes double membrane vacuole formation around bacteria in CF MDMs, while only single membrane vacuoles form in untreated CF cells. Bacterial burden is significantly reduced in autophagy stimulated CF MDMs, comparable to non-CF levels. IL-1β production is decreased in CF MDMs after IFN-γ treatment. Together, these results demonstrate that IFN-γ promotes autophagy-mediated clearance of B. cenocepacia in human CF macrophages. PMID:24798083

Four Decades of β-Lactam Antibiotic Pharmacokinetics in Cystic Fibrosis.

PubMed

Bulitta, Jürgen B; Jiao, Yuanyuan; Drescher, Stefanie K; Oliver, Antonio; Louie, Arnold; Moya, Bartolome; Tao, Xun; Wittau, Mathias; Tsuji, Brian T; Zavascki, Alexandre P; Shin, Beom Soo; Drusano, George L; Sörgel, Fritz; Landersdorfer, Cornelia B

2018-06-23

The pharmacokinetics (PK) of β-lactam antibiotics in cystic fibrosis (CF) patients has been compared with that in healthy volunteers for over four decades; however, no quantitative models exist that explain the PK differences between CF patients and healthy volunteers in older and newer studies. Our aims were to critically evaluate these studies and explain the PK differences between CF patients and healthy volunteers. We reviewed all 16 studies that compared the PK of β-lactams between CF patients and healthy volunteers within the same study. Analysis of covariance (ANCOVA) models were developed. In four early studies that compared adolescent, lean CF patients with adult healthy volunteers, clearance (CL) in CF divided by that in healthy volunteers was 1.72 ± 0.90 (average ± standard deviation); in four additional studies comparing age-matched (primarily adult) CF patients with healthy volunteers, this ratio was 1.46 ± 0.16. The CL ratio was 1.15 ± 0.11 in all eight studies that compared CF patients and healthy volunteers who were matched in age, body size and body composition, or that employed allometric scaling by lean body mass (LBM). Volume of distribution was similar between subject groups after scaling by body size. For highly protein-bound β-lactams, the unbound fraction was up to 2.07-fold higher in older studies that compared presumably sicker CF patients with healthy volunteers. These protein-binding differences explained over half of the variance for the CL ratio (p < 0.0001, ANCOVA). Body size, body composition and lower protein binding in presumably sicker CF patients explained the PK alterations in this population. Dosing CF patients according to LBM seems suitable to achieve antibiotic target exposures.

Mechanical analysis of carbon fiber reinforced shape memory polymer composite for self-deployable structure in space environment

NASA Astrophysics Data System (ADS)

Hong, Seok Bin; Ahn, Yong San; Jang, Joon Hyeok; Kim, Jin-Gyun; Goo, Nam Seo; Yu, Woong-Ryeol

2016-04-01

Shape memory polymer (SMP) is one of smart polymers which exhibit shape memory effect upon external stimuli. Reinforcements as carbon fiber had been used for making shape memory polymer composite (CF-SMPC). This study investigated a possibility of designing self-deployable structures in harsh space condition using CF-SMPCs and analyzed their shape memory behaviors with constitutive equation model.CF-SMPCs were prepared using woven carbon fabrics and a thermoset epoxy based SMP to obtain their basic mechanical properties including actuation in harsh environment. The mechanical and shape memory properties of SMP and CF-SMPCs were characterized using dynamic mechanical analysis (DMA) and universal tensile machine (UTM) with an environmental chamber. The mechanical properties such as flexural strength and tensile strength of SMP and CF-SMPC were measured with simple tensile/bending test and time dependent shape memory behavior was characterized with designed shape memory bending test. For mechanical analysis of CF-SMPCs, a 3D constitutive equation of SMP, which had been developed using multiplicative decomposition of the deformation gradient and shape memory strains, was used with material parameters determined from CF-SMPCs. Carbon fibers in composites reinforced tensile and flexural strength of SMP and acted as strong elastic springs in rheology based equation models. The actuation behavior of SMP matrix and CF-SMPCs was then simulated as 3D shape memory bending cases. Fiber bundle property was imbued with shell model for more precise analysis and it would be used for prediction of deploying behavior in self-deployable hinge structure.

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

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.

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.

Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressure

PubMed Central

Henderson, Ashley G.; Ehre, Camille; Button, Brian; Abdullah, Lubna H.; Cai, Li-Heng; Leigh, Margaret W.; DeMaria, Genevieve C.; Matsui, Hiro; Donaldson, Scott H.; Davis, C. William; Sheehan, John K.; Boucher, Richard C.; Kesimer, Mehmet

2014-01-01

The pathogenesis of mucoinfective lung disease in cystic fibrosis (CF) patients likely involves poor mucus clearance. A recent model of mucus clearance predicts that mucus flow depends on the relative mucin concentration of the mucus layer compared with that of the periciliary layer; however, mucin concentrations have been difficult to measure in CF secretions. Here, we have shown that the concentration of mucin in CF sputum is low when measured by immunologically based techniques, and mass spectrometric analyses of CF mucins revealed mucin cleavage at antibody recognition sites. Using physical size exclusion chromatography/differential refractometry (SEC/dRI) techniques, we determined that mucin concentrations in CF secretions were higher than those in normal secretions. Measurements of partial osmotic pressures revealed that the partial osmotic pressure of CF sputum and the retained mucus in excised CF lungs were substantially greater than the partial osmotic pressure of normal secretions. Our data reveal that mucin concentration cannot be accurately measured immunologically in proteolytically active CF secretions; mucins are hyperconcentrated in CF secretions; and CF secretion osmotic pressures predict mucus layer–dependent osmotic compression of the periciliary liquid layer in CF lungs. Consequently, mucin hypersecretion likely produces mucus stasis, which contributes to key infectious and inflammatory components of CF lung disease. PMID:24892808

Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy

NASA Astrophysics Data System (ADS)

Miller, Sharon J.; Lee, Cameron M.; Joshi, Bishnu P.; Gaustad, Adam; Seibel, Eric J.; Wang, Thomas D.

2012-02-01

Gastrointestinal cancers are heterogeneous and can overexpress several protein targets that can be imaged simultaneously on endoscopy using multiple molecular probes. We aim to demonstrate a multispectral scanning fiber endoscope for wide-field fluorescence detection of colonic dysplasia. Excitation at 440, 532, and 635 nm is delivered into a single spiral scanning fiber, and fluorescence is collected by a ring of light-collecting optical fibers placed around the instrument periphery. Specific-binding peptides are selected with phage display technology using the CPC;Apc mouse model of spontaneous colonic dysplasia. Validation of peptide specificity is performed on flow cytometry and in vivo endoscopy. The peptides KCCFPAQ, AKPGYLS, and LTTHYKL are selected and labeled with 7-diethylaminocoumarin-3-carboxylic acid (DEAC), 5-carboxytetramethylrhodamine (TAMRA), and CF633, respectively. Separate droplets of KCCFPAQ-DEAC, AKPGYLS-TAMRA, and LTTHYKL-CF633 are distinguished at concentrations of 100 and 1 μM. Separate application of the fluorescent-labeled peptides demonstrate specific binding to colonic adenomas. The average target/background ratios are 1.71+/-0.19 and 1.67+/-0.12 for KCCFPAQ-DEAC and AKPGYLS-TAMRA, respectively. Administration of these two peptides together results in distinct binding patterns in the blue and green channels. Specific binding of two or more peptides can be distinguished in vivo using a novel multispectral endoscope to localize colonic dysplasia on real-time wide-field imaging.

Technical note: Improving modeling of coagulation, curd firming, and syneresis of sheep milk.

PubMed

Cipolat-Gotet, Claudio; Pazzola, Michele; Ferragina, Alessandro; Cecchinato, Alessio; Dettori, Maria L; Vacca, Giuseppe M

2018-04-18

The importance of milk coagulation properties for milk processing, cheese yield, and quality is widely recognized. The use of traditional coagulation traits presents several limitations for testing bovine milk and even more for sheep milk, due to its rapid coagulation and curd firming, and early syneresis of coagulum. The aim of this technical note is to test and improve model fitting for assessing coagulation, curd firming, and syneresis of sheep milk. Using milk samples from 87 Sarda ewes, we performed in duplicate lactodynamographic testing. On each of the 174 analyzed milk aliquots, using 180 observations from each aliquot (one every 15 s for 45 min after rennet addition), we compared 4 different curd firming models as a function of time (CF t , mm) using a nonlinear procedure. The most accurate and informative results were observed using a modified 4-parameter model, structured as follows: [Formula: see text] , where t is time, RCT eq (min) is the gelation time, CF P (mm) is the potential asymptotical CF at an infinite time, k CF (%/min) is the curd firming rate constant, and k SR (%/min) is the curd syneresis rate constant. To avoid nonconvergence and computational problems due to interrelations among the equation parameters, CF P was preliminarily defined as a function of maximum observed curd firmness (CF max , mm) recorded during the analysis. For this model, all the modeling equations of individual sheep milk aliquots were converging, with a negligible standard error of the estimates (coefficient of determination >0.99 for all individual sample equations). Repeatability of the modeled parameters was acceptable, also in the presence of curd syneresis during the lactodynamographic analysis. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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

Postnatal airway growth in cystic fibrosis piglets.

PubMed

Adam, Ryan J; Abou Alaiwa, Mahmoud H; Bouzek, Drake C; Cook, Daniel P; Gansemer, Nicholas D; Taft, Peter J; Powers, Linda S; Stroik, Mallory R; Hoegger, Mark J; McMenimen, James D; Hoffman, Eric A; Zabner, Joseph; Welsh, Michael J; Meyerholz, David K; Stoltz, David A

2017-09-01

Mutations in the gene encoding the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) anion channel cause CF. The leading cause of death in the CF population is lung disease. Increasing evidence suggests that in utero airway development is CFTR-dependent and that developmental abnormalities may contribute to CF lung disease. However, relatively little is known about postnatal CF airway growth, largely because such studies are limited in humans. Therefore, we examined airway growth and lung volume in a porcine model of CF. We hypothesized that CF pigs would have abnormal postnatal airway growth. To test this hypothesis, we performed CT-based airway and lung volume measurements in 3-wk-old non-CF and CF pigs. We found that 3-wk-old CF pigs had tracheas of reduced caliber and irregular shape. Their bronchial lumens were reduced in size proximally but not distally, were irregularly shaped, and had reduced distensibility. Our data suggest that lack of CFTR results in aberrant postnatal airway growth and development, which could contribute to CF lung disease pathogenesis. NEW & NOTEWORTHY This CT scan-based study of airway morphometry in the cystic fibrosis (CF) postnatal period is unique, as analogous studies in humans are greatly limited for ethical and technical reasons. Findings such as reduced airway lumen area and irregular caliber suggest that airway growth and development are CF transmembrane conductance regulator-dependent and that airway growth defects may contribute to CF lung disease pathogenesis. Copyright © 2017 the American Physiological Society.

Mathematical model reveals role of nucleotide signaling in airway surface liquid homeostasis and its dysregulation in cystic fibrosis

PubMed Central

Sandefur, Conner I.; Boucher, Richard C.; Elston, Timothy C.

2017-01-01

Mucociliary clearance is composed of three components (i.e., mucin secretion, airway surface hydration, and ciliary-activity) which function coordinately to clear inhaled microbes and other foreign particles from airway surfaces. Airway surface hydration is maintained by water fluxes driven predominantly by active chloride and sodium ion transport. The ion channels that mediate electrogenic ion transport are regulated by extracellular purinergic signals that signal through G protein-coupled receptors. These purinoreceptors and the signaling pathways they activate have been identified as possible therapeutic targets for treating lung disease. A systems-level description of airway surface liquid (ASL) homeostasis could accelerate development of such therapies. Accordingly, we developed a mathematical model to describe the dynamic coupling of ion and water transport to extracellular purinergic signaling. We trained our model from steady-state and time-dependent experimental measurements made using normal and cystic fibrosis (CF) cultured human airway epithelium. To reproduce CF conditions, reduced chloride secretion, increased potassium secretion, and increased sodium absorption were required. The model accurately predicted ASL height under basal normal and CF conditions and the collapse of surface hydration due to the accelerated nucleotide metabolism associated with CF exacerbations. Finally, the model predicted a therapeutic strategy to deliver nucleotide receptor agonists to effectively rehydrate the ASL of CF airways. PMID:28808008

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.

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...

Carotid femoral pulse wave velocity in type 2 diabetes and hypertension: capturing arterial health effects of step counts

PubMed Central

Dasgupta, Kaberi; Rosenberg, Ellen; Joseph, Lawrence; Trudeau, Luc; Garfield, Natasha; Chan, Deborah; Sherman, Mark; Rabasa-Lhoret, Rémi; Daskalopoulou, Stella S.

2017-01-01

Objective: Optimal medication use obscures the impact of physical activity on traditional cardiometabolic risk factors. We evaluated the relationship between step counts and carotid-femoral pulse wave velocity (cfPWV), a summative risk indicator, in patients with type 2 diabetes and/or hypertension. Research design and methods: Three hundred and sixty-nine participants were recruited (outpatient clinics; Montreal, Quebec; 2011–2015). Physical activity (pedometer/accelerometer), cfPWV (applanation tonometry), and risk factors (A1C, Homeostatic Model Assessment–Insulin Resistance, blood pressure, lipid profiles) were evaluated. Linear regression models were constructed to quantify the relationship of steps/day with cfPWV. Results: The study population comprised 191 patients with type 2 diabetes and hypertension, 39 with type 2 diabetes, and 139 with hypertension (mean ± SD: age 59.6 ± 11.2 years; BMI 31.3 ± 4.8 kg/m2; 54.2% women). Blood pressure (125/77 ± 15/9 mmHg), A1C (diabetes: 7.7 ± 1.3%; 61 mmol/mol), and low-density lipoprotein cholesterol (diabetes: 2.19 ± 0.8 mmol/l; without diabetes: 3.13 ± 1.1mmol/l) were close to target. Participants averaged 5125 ± 2722 steps/day. Mean cfPWV was 9.8 ± 2.2 m/s. Steps correlated with cfPWV, but not with other risk factors. A 1000 steps/day increment was associated with a 0.1 m/s cfPWV decrement across adjusted models and in subgroup analysis by diabetes status. In a model adjusted for age, sex, BMI, ethnicity, immigrant status, employment, education, diabetes, hypertension, medication classes, the mean cfPWV decrement was 0.11 m/s (95% confidence interval −0.2, −0.02). Conclusions: cfPWV is responsive to step counts in patients who are well controlled on cardioprotective medications. This ability to capture the ‘added value’ of physical activity supports the emerging role of cfPWV in arterial health monitoring. PMID:28129250

Serum lipid level and lifestyles are associated with carotid femoral pulse wave velocity among adults: 4.4-year prospectively longitudinal follow-up of a clinical trial.

PubMed

Zhao, XiaoXiao; Wang, Hongyu; Bo, LiuJin; Zhao, Hongwei; Li, Lihong; Zhou, Yingyan

2018-01-01

Lifestyle modifications are recommended as the initial treatment for high blood pressure. The influence of dyslipidemia might be via moderate arterial stiffness, which results in hypertension and cardiovascular disease. We used data from a subgroup of the lifestyle, level of serum lipids/carotid femoral-pulse wave velocity (CF-PWV) Susceptibility BEST Study, a population-based study of community-dwelling adults aged 45-75 years. The serum lipid level and CF-PWV were measured at baseline, and lifestyle such as smoking status, sleeping habits, and the level of oil or salt intake was determined with the use of a validated questionnaire during follow-up. Arterial stiffness was determined as CF-PWV using an electrocardiogram after a mean follow-up of 4.4 years. Regression coefficients (95% CIs), adjusted for demographics, risk factors, cholesterol, and triglycerides (TGs), were calculated by linear regression. Logistic regression analysis was used to identify the association between the variables with CF-PWV independently. In the results, glucose and total cholesterol (TC) were associated with higher CF-PWV (p = 0.000) and lower-destiny lipoprotein was associated with lower CF-PWV (p = 0.001) after adjustments for age, sex, mean arterial pressure, and heart rate. There were significant associations observed for current salt intake in relation to CF-PWV (p-trend = 0.038) without adjustment. This association was retained after adjustments for covariates and had statistical significance (p-trend = 0.048) in model 3, which adjusted age, sex, baseline CF-PWV, mean arterial pressure, heart rate waist circumference, education, smoking status, physical activity, diabetes mellitus (DM), heart disease, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, TGs, antihypertensive medicine, nitrate medicine, and antiplatelet medicine. Linear regression showed statistically significant associations between LDL and CF-PWV in the fully adjusted models (model 1 p = 0.010, model 2 p = 0.020, model 3 p = 0.017). Logistic regression analysis showed that CF-PWV was independently associated with age (p = 0.000), TC (p = 0.000), TGs (p = 0.000), and homo-cysteine (p = 0.000), and their odds ratios were 0.781, 3.424, 0.075, and 1.046, respectively. Our results showed a positive association between LDL and arterial stiffness, and suggested that less smoking status, sleeping disorder, and salt intake were associated with less arterial stiffness.

Optimization of Causative Factors for Landslide Susceptibility Evaluation Using Remote Sensing and GIS Data in Parts of Niigata, Japan.

PubMed

Dou, Jie; Tien Bui, Dieu; Yunus, Ali P; Jia, Kun; Song, Xuan; Revhaug, Inge; Xia, Huan; Zhu, Zhongfan

2015-01-01

This paper assesses the potentiality of certainty factor models (CF) for the best suitable causative factors extraction for landslide susceptibility mapping in the Sado Island, Niigata Prefecture, Japan. To test the applicability of CF, a landslide inventory map provided by National Research Institute for Earth Science and Disaster Prevention (NIED) was split into two subsets: (i) 70% of the landslides in the inventory to be used for building the CF based model; (ii) 30% of the landslides to be used for the validation purpose. A spatial database with fifteen landslide causative factors was then constructed by processing ALOS satellite images, aerial photos, topographical and geological maps. CF model was then applied to select the best subset from the fifteen factors. Using all fifteen factors and the best subset factors, landslide susceptibility maps were produced using statistical index (SI) and logistic regression (LR) models. The susceptibility maps were validated and compared using landslide locations in the validation data. The prediction performance of two susceptibility maps was estimated using the Receiver Operating Characteristics (ROC). The result shows that the area under the ROC curve (AUC) for the LR model (AUC = 0.817) is slightly higher than those obtained from the SI model (AUC = 0.801). Further, it is noted that the SI and LR models using the best subset outperform the models using the fifteen original factors. Therefore, we conclude that the optimized factor model using CF is more accurate in predicting landslide susceptibility and obtaining a more homogeneous classification map. Our findings acknowledge that in the mountainous regions suffering from data scarcity, it is possible to select key factors related to landslide occurrence based on the CF models in a GIS platform. Hence, the development of a scenario for future planning of risk mitigation is achieved in an efficient manner.

Optimization of Causative Factors for Landslide Susceptibility Evaluation Using Remote Sensing and GIS Data in Parts of Niigata, Japan

PubMed Central

Dou, Jie; Tien Bui, Dieu; P. Yunus, Ali; Jia, Kun; Song, Xuan; Revhaug, Inge; Xia, Huan; Zhu, Zhongfan

2015-01-01

This paper assesses the potentiality of certainty factor models (CF) for the best suitable causative factors extraction for landslide susceptibility mapping in the Sado Island, Niigata Prefecture, Japan. To test the applicability of CF, a landslide inventory map provided by National Research Institute for Earth Science and Disaster Prevention (NIED) was split into two subsets: (i) 70% of the landslides in the inventory to be used for building the CF based model; (ii) 30% of the landslides to be used for the validation purpose. A spatial database with fifteen landslide causative factors was then constructed by processing ALOS satellite images, aerial photos, topographical and geological maps. CF model was then applied to select the best subset from the fifteen factors. Using all fifteen factors and the best subset factors, landslide susceptibility maps were produced using statistical index (SI) and logistic regression (LR) models. The susceptibility maps were validated and compared using landslide locations in the validation data. The prediction performance of two susceptibility maps was estimated using the Receiver Operating Characteristics (ROC). The result shows that the area under the ROC curve (AUC) for the LR model (AUC = 0.817) is slightly higher than those obtained from the SI model (AUC = 0.801). Further, it is noted that the SI and LR models using the best subset outperform the models using the fifteen original factors. Therefore, we conclude that the optimized factor model using CF is more accurate in predicting landslide susceptibility and obtaining a more homogeneous classification map. Our findings acknowledge that in the mountainous regions suffering from data scarcity, it is possible to select key factors related to landslide occurrence based on the CF models in a GIS platform. Hence, the development of a scenario for future planning of risk mitigation is achieved in an efficient manner. PMID:26214691

Multiple Functional Domains of Enterococcus faecalis Aggregation Substance Asc10 Contribute to Endocarditis Virulence ▿ †

PubMed Central

Chuang, Olivia N.; Schlievert, Patrick M.; Wells, Carol L.; Manias, Dawn A.; Tripp, Timothy J.; Dunny, Gary M.

2009-01-01

Aggregation substance proteins encoded by sex pheromone plasmids increase the virulence of Enterococcus faecalis in experimental pathogenesis models, including infectious endocarditis models. These large surface proteins may contain multiple functional domains involved in various interactions with other bacterial cells and with the mammalian host. Aggregation substance Asc10, encoded by plasmid pCF10, is induced during growth in the mammalian bloodstream, and pCF10 carriage gives E. faecalis a significant selective advantage in this environment. We employed a rabbit model to investigate the role of various functional domains of Asc10 in endocarditis. The data suggested that the bacterial load of the infected tissue was the best indicator of virulence. Isogenic strains carrying either no plasmid, wild-type pCF10, a pCF10 derivative with an in-frame deletion of the prgB gene encoding Asc10, or pCF10 derivatives expressing other alleles of prgB were examined in this model. Previously identified aggregation domains contributed to the virulence associated with the wild-type protein, and a strain expressing an Asc10 derivative in which glycine residues in two RGD motifs were changed to alanine residues showed the greatest reduction in virulence. Remarkably, this strain and the strain carrying the pCF10 derivative with the in-frame deletion of prgB were both significantly less virulent than an isogenic plasmid-free strain. The data demonstrate that multiple functional domains are important in Asc10-mediated interactions with the host during the course of experimental endocarditis and that in the absence of a functional prgB gene, pCF10 carriage is actually disadvantageous in vivo. PMID:18955479

Apple Peel Supplemented Diet Reduces Parameters of Metabolic Syndrome and Atherogenic Progression in ApoE-/- Mice.

PubMed

Gonzalez, Jaime; Donoso, Wendy; Sandoval, Nathalie; Reyes, María; Gonzalez, Priscila; Gajardo, Monica; Morales, Erik; Neira, Amalia; Razmilic, Iván; Yuri, José A; Moore-Carrasco, Rodrigo

2015-01-01

Cardiovascular Diseases (CVD) represent about 30% of all causes of death worldwide. The development of CVD is related in many cases with the previous existence of metabolic syndrome (MS). It is known that apple consumption has a cardiovascular protecting effect, containing phenolic compounds with antioxidant effect, which are concentrated in the fruit peel. The objective of this study was to test the effect of apple peel consumption in a murine model of MS and apoE-/- mice. Apple supplemented diets reduced the biochemical parameters (glycaemia, total cholesterol, HDL-cholesterol, LDL-cholesterol, ureic nitrogen, triglycerides, insulin, and asymmetric dimethylarginine (ADMA)) of MS model in CF1 mice significantly. The model apoE-/- mouse was used to evaluate the capacity of the apple peel to revert the progression of the atherogenesis. FD with HAP reverts cholesterol significantly and slows down the progression of the plate diminishing the cholesterol accumulation area. With these results, it can be concluded that the consumption of apple peel reduces several MS parameters and the atherogenic progression in mice.

Apple Peel Supplemented Diet Reduces Parameters of Metabolic Syndrome and Atherogenic Progression in ApoE−/− Mice

PubMed Central

Gonzalez, Jaime; Donoso, Wendy; Sandoval, Nathalie; Reyes, María; Gonzalez, Priscila; Gajardo, Monica; Morales, Erik; Neira, Amalia; Razmilic, Iván; Yuri, José A.

2015-01-01

Cardiovascular Diseases (CVD) represent about 30% of all causes of death worldwide. The development of CVD is related in many cases with the previous existence of metabolic syndrome (MS). It is known that apple consumption has a cardiovascular protecting effect, containing phenolic compounds with antioxidant effect, which are concentrated in the fruit peel. The objective of this study was to test the effect of apple peel consumption in a murine model of MS and apoE−/− mice. Apple supplemented diets reduced the biochemical parameters (glycaemia, total cholesterol, HDL-cholesterol, LDL-cholesterol, ureic nitrogen, triglycerides, insulin, and asymmetric dimethylarginine (ADMA)) of MS model in CF1 mice significantly. The model apoE−/− mouse was used to evaluate the capacity of the apple peel to revert the progression of the atherogenesis. FD with HAP reverts cholesterol significantly and slows down the progression of the plate diminishing the cholesterol accumulation area. With these results, it can be concluded that the consumption of apple peel reduces several MS parameters and the atherogenic progression in mice. PMID:26075004

Should cell-free DNA testing be used to target antenatal rhesus immune globulin administration?

PubMed

Ma, Kimberly K; Rodriguez, Maria I; Cheng, Yvonne W; Norton, Mary E; Caughey, Aaron B

2016-01-01

To compare the rates of alloimmunization with the use of cell-free DNA (cfDNA) screening to target antenatal rhesus immune globulin (RhIG) prenatally, versus routine administration of RhIG in rhesus D (RhD)-negative pregnant women in a theoretic cohort using a decision-analytic model. A decision-analytic model compared cfDNA testing to routine antenatal RhIG administration. The primary outcome was maternal sensitization to RhD antigen. Sensitivity and specificity of cfDNA testing were assumed to be 99.8% and 95.3%, respectively. Univariate and bivariate sensitivity analyses, Monte Carlo simulation, and threshold analyses were performed. In a cohort of 10,000 RhD-negative women, 22.6 sensitizations would occur with utilization of cfDNA, while 20 sensitizations would occur with routine RhIG. Only when the sensitivity of the cfDNA test reached 100%, the rate of sensitization was equal for both cfDNA and RhIG. Otherwise, routine RhIG minimized the rate of sensitization, especially given RhIG is readily available in the United States. Adoption of cfDNA testing would result in a 13.0% increase in sensitization among RhD-negative women in a theoretical cohort taking into account the ethnic diversity of the United States' population.

Proposed reference models for CO2 and halogenated hydrocarbons

NASA Technical Reports Server (NTRS)

Fabian, P.

1989-01-01

The vertical distribution of carbon dioxide, halocarbons and their sink products, HCl and HF, have become available, mainly by means of balloon measurements. Most measurements were made at northern mid-latutudes, but some constituents were measured at tropical latitudes and in the Southern Hemisphere as well. An attempt is made here to combine the available data for presentation of reference models for CO2, CCl4 CCl3F, CCl2F2, CClF3, CF4, CCl2F-CClF2, CClF2-CClF2, CClF2-CF3, CF3-CF3, CH3Cl, CHClF2, CH3-CCl3, CBrClF2, CBrF3, HCl and HF.

Compassion fatigue, burnout and compassion satisfaction among family physicians in the Negev area - a cross-sectional study.

PubMed

El-Bar, Nurit; Levy, Amalia; Wald, Hedy S; Biderman, Aya

2013-08-15

Compassion fatigue among health care professionals has gained interest over the past decade. Compassion fatigue, as well as burnout, has been associated with depersonalization and suboptimal patient care. Professional caregivers in general are exposed to the risk of compassion fatigue (CF), burnout (BO) and low levels of compassion satisfaction (CS). While CF has been studied in health care professionals, few publications address its incidence among family physicians, specifically. The objectives of this study were to assess the prevalence and severity of CF among family practitioners (FPs) in the Negev (Israel's southern region), evaluating the correlations between CF, BO and CS and their relations with socio-demographic variables and work related characteristics. Self-report anonymous Compassion Satisfaction and Fatigue Test questionnaires (CSFT) measuring CF, BO, and CS were distributed among 194 family physicians at Clalit Health Services clinics in the Negev between July 2007 and April 2008. Correlations between CF, BO and CS were assessed. Multivariable logistic regression models with backward elimination were constructed. 128 (66%) physicians responded. 46.1% of respondents scored extremely high and high for CF, 21.1% scored low for CS and 9.4% scored high for BO. Strong correlations were found between BO and CF (r = 0.769, p < 0.001), and between BO and CS (r = -0.241, p = 0.006), but no correlation was found between CS and CF. The logistic regression model showed that the only factor associated with a significantly increased risk for CF was former immigration to Israel. Increased risk for BO was associated with female gender, history of personal trauma and lack of academic affiliation. Higher CS was associated with holding management positions and teaching residents. Family physicians in the Negev are at high risk for CF, with the potential for CF- associated patient dissatisfaction, compromised patient safety and increased medical error. We propose creation of a CF educational and early intervention treatment program for family physicians and other health care professionals. Such programs would train facilitators of physician well-being and resiliency building. We also recommend analyzing contributing variables and organizational factors related to higher CF. Policy recommendations include integrating such programs within required risk management continuing medical education.

Compassion fatigue, burnout and compassion satisfaction among family physicians in the Negev area - a cross-sectional study

PubMed Central

2013-01-01

Background Compassion fatigue among health care professionals has gained interest over the past decade. Compassion fatigue, as well as burnout, has been associated with depersonalization and suboptimal patient care. Professional caregivers in general are exposed to the risk of compassion fatigue (CF), burnout (BO) and low levels of compassion satisfaction (CS). While CF has been studied in health care professionals, few publications address its incidence among family physicians, specifically. The objectives of this study were to assess the prevalence and severity of CF among family practitioners (FPs) in the Negev (Israel’s southern region), evaluating the correlations between CF, BO and CS and their relations with socio-demographic variables and work related characteristics. Methods Self-report anonymous Compassion Satisfaction and Fatigue Test questionnaires (CSFT) measuring CF, BO, and CS were distributed among 194 family physicians at Clalit Health Services clinics in the Negev between July 2007 and April 2008. Correlations between CF, BO and CS were assessed. Multivariable logistic regression models with backward elimination were constructed. Results 128 (66%) physicians responded. 46.1% of respondents scored extremely high and high for CF, 21.1% scored low for CS and 9.4% scored high for BO. Strong correlations were found between BO and CF (r = 0.769, p < 0.001), and between BO and CS (r = −0.241, p = 0.006), but no correlation was found between CS and CF. The logistic regression model showed that the only factor associated with a significantly increased risk for CF was former immigration to Israel. Increased risk for BO was associated with female gender, history of personal trauma and lack of academic affiliation. Higher CS was associated with holding management positions and teaching residents. Conclusions and policy recommendations Family physicians in the Negev are at high risk for CF, with the potential for CF- associated patient dissatisfaction, compromised patient safety and increased medical error. We propose creation of a CF educational and early intervention treatment program for family physicians and other health care professionals. Such programs would train facilitators of physician well-being and resiliency building. We also recommend analyzing contributing variables and organizational factors related to higher CF. Policy recommendations include integrating such programs within required risk management continuing medical education. PMID:23947591

Individual Patterns of Complexity in Cystic Fibrosis Lung Microbiota, Including Predator Bacteria, over a 1-Year Period.

PubMed

de Dios Caballero, Juan; Vida, Rafael; Cobo, Marta; Máiz, Luis; Suárez, Lucrecia; Galeano, Javier; Baquero, Fernando; Cantón, Rafael; Del Campo, Rosa

2017-09-26

Cystic fibrosis (CF) lung microbiota composition has recently been redefined by the application of next-generation sequencing (NGS) tools, identifying, among others, previously undescribed anaerobic and uncultivable bacteria. In the present study, we monitored the fluctuations of this ecosystem in 15 CF patients during a 1-year follow-up period, describing for the first time, as far as we know, the presence of predator bacteria in the CF lung microbiome. In addition, a new computational model was developed to ascertain the hypothetical ecological repercussions of a prey-predator interaction in CF lung microbial communities. Fifteen adult CF patients, stratified according to their pulmonary function into mild ( n = 5), moderate ( n = 9), and severe ( n = 1) disease, were recruited at the CF unit of the Ramón y Cajal University Hospital (Madrid, Spain). Each patient contributed three or four induced sputum samples during a 1-year follow-up period. Lung microbiota composition was determined by both cultivation and NGS techniques and was compared with the patients' clinical variables. Results revealed a particular microbiota composition for each patient that was maintained during the study period, although some fluctuations were detected without any clinical correlation. For the first time, Bdellovibrio and Vampirovibrio predator bacteria were shown in CF lung microbiota and reduced-genome bacterial parasites of the phylum Parcubacteria were also consistently detected. The newly designed computational model allows us to hypothesize that inoculation of predators into the pulmonary microbiome might contribute to the control of chronic colonization by CF pathogens in early colonization stages. IMPORTANCE The application of NGS to sequential samples of CF patients demonstrated the complexity of the organisms present in the lung (156 species) and the constancy of basic individual colonization patterns, although some differences between samples from the same patient were observed, probably related to sampling bias. Bdellovibrio and Vampirovibrio predator bacteria were found for the first time by NGS as part of the CF lung microbiota, although their ecological significance needs to be clarified. The newly designed computational model allows us to hypothesize that inoculation of predators into the lung microbiome can eradicate CF pathogens in early stages of the process. Our data strongly suggest that lower respiratory microbiome fluctuations are not necessarily related to the patient's clinical status. Copyright © 2017 de Dios Caballero et al.

Investigation of pre-pubertal sex differences in wheel running and social behavior in three mouse strains

PubMed Central

Gordon, Elizabeth A.; Corbitt, Cynthia

2015-01-01

Sex differences in social behaviors exist in mammals during adulthood, and further evidence suggests that sex differences in behavior are present before sexual maturity. In order to model behavioral disorders in animals, it is important to assess baseline sex-related behavioral differences, especially when studying disorders for which sex-related behavioral effects are expected. We investigated the effect of sex on behavior in 3 strains of pre-pubertal mice (C57BL/6, CFW, and CF1) using a wheel-running assay. We found no significant sex differences in latency to run on the wheel or total duration of wheel running within each strain. During the social interaction test, there were no differences between sexes in latency or total duration of contact or following between a subject and novel mouse. We also evaluated behavioral patterns of wheel running and stereotypical behaviors, such as burrowing and grooming. Both sexes showed characteristic wheel running behavior, spending the majority of each trial interacting with the wheel when it was free and more time performing other activities (e.g., stereotypical behaviors, general locomotion) when it was jammed. These results provide evidence that, among various strains of pre-pubertal mice, baseline sex-related behavioral differences are not strong enough to influence the measured behaviors. PMID:26316671

Investigation of pre-pubertal sex differences in wheel running and social behavior in three mouse strains.

PubMed

Gordon, Elizabeth A; Corbitt, Cynthia

2015-08-01

Sex differences in social behaviors exist in mammals during adulthood, and further evidence suggests that sex differences in behavior are present before sexual maturity. In order to model behavioral disorders in animals, it is important to assess baseline sex-related behavioral differences, especially when studying disorders for which sex-related behavioral effects are expected. We investigated the effect of sex on behavior in 3 strains of pre-pubertal mice (C57BL/6, CFW, and CF1) using a wheel-running assay. We found no significant sex differences in latency to run on the wheel or total duration of wheel running within each strain. During the social interaction test, there were no differences between sexes in latency or total duration of contact or following between a subject and novel mouse. We also evaluated behavioral patterns of wheel running and stereotypical behaviors, such as burrowing and grooming. Both sexes showed characteristic wheel running behavior, spending the majority of each trial interacting with the wheel when it was free and more time performing other activities ( e.g. , stereotypical behaviors, general locomotion) when it was jammed. These results provide evidence that, among various strains of pre-pubertal mice, baseline sex-related behavioral differences are not strong enough to influence the measured behaviors.

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

Effects of Frequency Spreads on Beam Breakup Instabilities in Linear Accelerators

DTIC Science & Technology

1989-05-11

i - 1)A/(N - 1), i = 1, ....N. In keeping with the above model [ cf . Eq. (4)], we assume that there is an equal probability (1/N) for each of these...solution (5), which contains two approximations to (10) and (11) [ cf ., N 4 - limit, and then asymptotic analysis], could accurately model the numerical...that the transition time Tl = 0(1) is the time when the phase mixing factor A0 t is roughly balanced by the BBU exponentiation factoro 1.64W I / 3 [ cf

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.

Analysis of contributing factors associated to related patients safety incidents in Intensive Care Medicine.

PubMed

Martín Delgado, M C; Merino de Cos, P; Sirgo Rodríguez, G; Álvarez Rodríguez, J; Gutiérrez Cía, I; Obón Azuara, B; Alonso Ovies, Á

2015-01-01

To explore contributing factors (CF) associated to related critical patients safety incidents. SYREC study pos hoc analysis. A total of 79 Intensive Care Departments were involved. The study sample consisted of 1.017 patients; 591 were affected by one or more incidents. The CF were categorized according to a proposed model by the National Patient Safety Agency from United Kingdom that was modified. Type, class and severity of the incidents was analyzed. A total 2,965 CF were reported (1,729 were associated to near miss and 1,236 to adverse events). The CF group more frequently reported were related patients factors. Individual factors were reported more frequently in near miss and task related CF in adverse events. CF were reported in all classes of incidents. The majority of CF were reported in the incidents classified such as less serious, even thought CF patients factors were associated to serious incidents. Individual factors were considered like avoidable and patients factors as unavoidable. The CF group more frequently reported were patient factors and was associated to more severe and unavoidable incidents. By contrast, individual factors were associated to less severe and avoidable incidents. In general, CF most frequently reported were associated to near miss. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Transplant center volume and outcomes in lung transplantation for cystic fibrosis.

PubMed

Hayes, Don; Sweet, Stuart C; Benden, Christian; Kopp, Benjamin T; Goldfarb, Samuel B; Visner, Gary A; Mallory, George B; Tobias, Joseph D; Tumin, Dmitry

2017-04-01

Transplant volume represents lung transplant (LTx) expertise and predicts outcomes, so we sought to determine outcomes related to center volumes in cystic fibrosis (CF). United Network for Organ Sharing data were queried for patients with CF in the United States (US) receiving bilateral LTx from 2005 to 2015. Multivariable Cox regression was used to model survival to 1 year and long-term (>1 year) survival, conditional on surviving at least 1 year. A total of 2025 patients and 67 centers were included in the analysis. The median annual LTx volumes were three in CF [interquartile range (IQR): 2, 6] and 17 in non-CF (IQR: 8, 33). Multivariable Cox regression in cases with complete data and surviving at least 1 year (n = 1510) demonstrated that greater annual CF LTx volume (HR per 10 LTx = 0.66; 95% CI: 0.49, 0.89; P = 0.006) but not greater non-CF LTx volume (HR = 1.00; 95% CI: 0.96, 1.05; P = 0.844) was associated with improved long-term survival in LTx recipients with CF. A Wald interaction test confirmed that CF LTx volume was more strongly associated with long-term outcomes than non-CF LTx volume (P = 0.012). In a US cohort, center volume was not associated with 1-year survival. CF-specific expertise predicted improved long-term outcomes of LTx for CF, whereas general LTx expertise was unassociated with CF patients' survival. © 2016 Steunstichting ESOT.

RNA sequencing data from neutrophils of patients with cystic fibrosis reveals potential for developing biomarkers for pulmonary exacerbations.

PubMed

Jiang, Kaiyu; Poppenberg, Kerry E; Wong, Laiping; Chen, Yanmin; Borowitz, Drucy; Goetz, Danielle; Sheehan, Daniel; Frederick, Carla; Tutino, Vincent M; Meng, Hui; Jarvis, James N

2018-06-22

There is no effective way to predict cystic fibrosis (CF) pulmonary exacerbations (CFPE) before they become symptomatic or to assess satisfactory treatment responses. RNA sequencing of peripheral blood neutrophils from CF patients before and after therapy for CFPE was used to create transcriptome profiles. Transcripts with an average transcripts per million (TPM) level > 1.0 and a false discovery rate (FDR) < 0.05 were used in a cosine K-nearest neighbor (KNN) model. Real time PCR was used to corroborate RNA sequencing expression differences in both neutrophils and whole blood samples from an independent cohort of CF patients. Furthermore, sandwich ELISA was conducted to assess plasma levels of MRP8/14 complexes in CF patients before and after therapy. We found differential expression of 136 transcripts and 83 isoforms when we compared neutrophils from CF patients before and after therapy (>1.5 fold change, FDR-adjusted P < 0.05). The model was able to successfully separate CF flare samples from those taken from the same patients in convalescence with an accuracy of 0.75 in both the training and testing cohorts. Six differently expressed genes were confirmed by real time PCR using both isolated neutrophils and whole blood from an independent cohort of CF patients before and after therapy, even though levels of myeloid related protein MRP8/14 dimers in plasma of CF patients were essentially unchanged by therapy. Our findings demonstrate the potential of machine learning approaches for classifying disease states and thus developing sensitive biomarkers that can be used to monitor pulmonary disease activity in CF. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

An exploration of the experience of compassion fatigue in clinical oncology nurses.

PubMed

Perry, Beth; Toffner, Greg; Merrick, Trish; Dalton, Janice

2011-01-01

Compassion fatigue (CF) is "debilitating weariness brought about by repetitive, empathic responses to the pain and suffering of others" (LaRowe, 2005, p. 21). The work performed by oncology nurses, and the experiences of the people they care for, place oncology nurses at high risk for CF (Pierce et al., 2007; Ferrell & Coyle, 2008). Thus oncology nurses were chosen as the study focus. This paper details a descriptive exploratory qualitative research study that investigated the experience of CF in Canadian clinical oncology registered nurses (RNs). A conceptual stress process model by Aneshensel, Pearlin, Mullan, Zarit, and Whitlatch (1995) that considers caregivers' stress in four domains provided the study framework (see Figure 1). Nineteen study participants were recruited through an advertisement in the Canadian Oncology Nursing Journal (CONJ). The advertisement directed potential participants to a university-based online website developed for this study. Participants completed a questionnaire and wrote a narrative describing an experience with CF and submitted these through the secure research website. Data were analyzed thematically. Five themes include: defining CF, causes of CF, factors that worsen CF, factors that lessen CF, and outcomes of CF. Participants had limited knowledge about CF, about lack of external support, and that insufficient time to provide high quality, care may precipitate CF. The gap between quality of care nurses wanted to provide and what they were able to do, compounded by coexisting physical and emotional stress, worsened CF. CF was lessened by colleague support, work-life balance, connecting with others, acknowledgement, and maturity and experience. Outcomes of CF included profound fatigue of mind and body, negative effects on personal relationships, and considering leaving the specialty. Recommendations that may enhance oncology nurse well-being are provided.

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.

A theoretical study of resin flows for thermosetting materials during prepreg processing

NASA Technical Reports Server (NTRS)

Hou, T. H.

1984-01-01

A flow model which describes the process of resin consolidation during prepreg lamination was developed. The salient features of model predictions were explored. It is assumed that resin flows in all directions originate from squeezing action between two approaching adjacent fiber/fabric layers. In the horizontal direction, a squeezing flow between two nonporous parallel plates is analyzed, while in the vertical direction a poiseuille type pressure flow through porous media is assumed. Proper force and mass balance was established for the whole system which is composed of these two types of flow. A flow parameter, CF, shows to be a measure of processibility for the curing resin. For a given external load-F the responses of resin flow during prepreg lamination, as measured by CF, are categorized into three regions: (1) the low CF region where resin flows are inhibited by the high chemoviscosity during initial curing stages; (2) the median CF region where resin flows are properly controllable; and (3) the high CF region where resin flows are ceased due to fiber/fabric compression effects. Resin losses in both directions are calculated. Potential uses of this model and quality control of incoming prepreg material are discussed.

Targeting the Bacterial Cytoskeleton of the Burkholderia cepacia Complex for Antimicrobial Development: A Cautionary Tale.

PubMed

Carnell, Sonya C; Perry, John D; Borthwick, Lee; Vollmer, Daniela; Biboy, Jacob; Facchini, Marcella; Bragonzi, Alessandra; Silipo, Alba; Vergunst, Annette C; Vollmer, Waldemar; Khan, Anjam C M; De Soyza, Anthony

2018-05-30

Burkholderia cepacia complex (BCC) bacteria are a group of opportunistic pathogens that cause severe lung infections in cystic fibrosis (CF). Treatment of BCC infections is difficult, due to the inherent and acquired multidrug resistance of BCC. There is a pressing need to find new bacterial targets for antimicrobials. Here, we demonstrate that the novel compound Q22, which is related to the bacterial cytoskeleton destabilising compound A22, can reduce the growth rate and inhibit growth of BCC bacteria. We further analysed the phenotypic effects of Q22 treatment on BCC virulence traits, to assess its feasibility as an antimicrobial. BCC bacteria were grown in the presence of Q22 with a broad phenotypic analysis, including resistance to H₂O₂-induced oxidative stress, changes in the inflammatory potential of cell surface components, and in-vivo drug toxicity studies. The influence of the Q22 treatment on inflammatory potential was measured by monitoring the cytokine responses of BCC whole cell lysates, purified lipopolysaccharide, and purified peptidoglycan extracted from bacterial cultures grown in the presence or absence of Q22 in differentiated THP-1 cells. BCC bacteria grown in the presence of Q22 displayed varying levels of resistance to H₂O₂-induced oxidative stress, with some strains showing increased resistance after treatment. There was strain-to-strain variation in the pro-inflammatory ability of bacterial lysates to elicit TNFα and IL-1β from human myeloid cells. Despite minimal toxicity previously shown in vitro with primary CF cell lines, in-vivo studies demonstrated Q22 toxicity in both zebrafish and mouse infection models. In summary, destabilisation of the bacterial cytoskeleton in BCC, using compounds such as Q22, led to increased virulence-related traits in vitro. These changes appear to vary depending on strain and BCC species. Future development of antimicrobials targeting the BCC bacterial cytoskeleton may be hampered if such effects translate into the in-vivo environment of the CF infection.

Enhancement of Arterial Pressure Pulsatility by Controlling Continuous-Flow Left Ventricular Assist Device Flow Rate in Mock Circulatory System.

PubMed

Bozkurt, Selim; van de Vosse, Frans N; Rutten, Marcel C M

Continuous-flow left ventricular assist devices (CF-LVADs) generally operate at a constant speed, which reduces pulsatility in the arteries and may lead to complications such as functional changes in the vascular system, gastrointestinal bleeding, or both. The purpose of this study is to increase the arterial pulse pressure and pulsatility by controlling the CF-LVAD flow rate. A MicroMed DeBakey pump was used as the CF-LVAD. A model simulating the flow rate through the aortic valve was used as a reference model to drive the pump. A mock circulation containing two synchronized servomotor-operated piston pumps acting as left and right ventricles was used as a circulatory system. Proportional-integral control was used as the control method. First, the CF-LVAD was operated at a constant speed. With pulsatile-speed CF-LVAD assistance, the pump was driven such that the same mean pump output was generated. Continuous and pulsatile-speed CF-LVAD assistance provided the same mean arterial pressure and flow rate, while the index of pulsatility increased significantly for both arterial pressure and pump flow rate signals under pulsatile speed pump support. This study shows the possibility of improving the pulsatility of CF-LVAD support by regulating pump speed over a cardiac cycle without reducing the overall level of support.

Increased apical Na+ permeability in cystic fibrosis is supported by a quantitative model of epithelial ion transport

PubMed Central

O’Donoghue, Donal L; Dua, Vivek; Moss, Guy W J; Vergani, Paola

2013-01-01

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes an anion channel. In the human lung CFTR loss causes abnormal ion transport across airway epithelial cells. As a result CF individuals produce thick mucus, suffer persistent bacterial infections and have a much reduced life expectancy. Trans-epithelial potential difference (Vt) measurements are routinely carried out on nasal epithelia of CF patients in the clinic. CF epithelia exhibit a hyperpolarised basal Vt and a larger Vt change in response to amiloride (a blocker of the epithelial Na+ channel, ENaC). Are these altered bioelectric properties solely a result of electrical coupling between the ENaC and CFTR currents, or are they due to an increased ENaC permeability associated with CFTR loss? To examine these issues we have developed a quantitative mathematical model of human nasal epithelial ion transport. We find that while the loss of CFTR permeability hyperpolarises Vt and also increases amiloride-sensitive Vt, these effects are too small to account for the magnitude of change observed in CF epithelia. Instead, a parallel increase in ENaC permeability is required to adequately fit observed experimental data. Our study provides quantitative predictions for the complex relationships between ionic permeabilities and nasal Vt, giving insights into the physiology of CF disease that have important implications for CF therapy. PMID:23732645

Individual Patterns of Complexity in Cystic Fibrosis Lung Microbiota, Including Predator Bacteria, over a 1-Year Period

PubMed Central

de Dios Caballero, Juan; Vida, Rafael; Cobo, Marta; Máiz, Luis; Suárez, Lucrecia; Galeano, Javier; Baquero, Fernando; Cantón, Rafael

2017-01-01

ABSTRACT Cystic fibrosis (CF) lung microbiota composition has recently been redefined by the application of next-generation sequencing (NGS) tools, identifying, among others, previously undescribed anaerobic and uncultivable bacteria. In the present study, we monitored the fluctuations of this ecosystem in 15 CF patients during a 1-year follow-up period, describing for the first time, as far as we know, the presence of predator bacteria in the CF lung microbiome. In addition, a new computational model was developed to ascertain the hypothetical ecological repercussions of a prey-predator interaction in CF lung microbial communities. Fifteen adult CF patients, stratified according to their pulmonary function into mild (n = 5), moderate (n = 9), and severe (n = 1) disease, were recruited at the CF unit of the Ramón y Cajal University Hospital (Madrid, Spain). Each patient contributed three or four induced sputum samples during a 1-year follow-up period. Lung microbiota composition was determined by both cultivation and NGS techniques and was compared with the patients’ clinical variables. Results revealed a particular microbiota composition for each patient that was maintained during the study period, although some fluctuations were detected without any clinical correlation. For the first time, Bdellovibrio and Vampirovibrio predator bacteria were shown in CF lung microbiota and reduced-genome bacterial parasites of the phylum Parcubacteria were also consistently detected. The newly designed computational model allows us to hypothesize that inoculation of predators into the pulmonary microbiome might contribute to the control of chronic colonization by CF pathogens in early colonization stages. PMID:28951476

Family of columns isospectral to gravity-loaded columns with tip force: A discrete approach

NASA Astrophysics Data System (ADS)

Ramachandran, Nirmal; Ganguli, Ranjan

2018-06-01

A discrete model is introduced to analyze transverse vibration of straight, clamped-free (CF) columns of variable cross-sectional geometry under the influence of gravity and a constant axial force at the tip. The discrete model is used to determine critical combinations of loading parameters - a gravity parameter and a tip force parameter - that cause onset of dynamic instability in the CF column. A methodology, based on matrix-factorization, is described to transform the discrete model into a family of models corresponding to weightless and unloaded clamped-free (WUCF) columns, each with a transverse vibration spectrum isospectral to the original model. Characteristics of models in this isospectral family are dependent on three transformation parameters. A procedure is discussed to convert the isospectral discrete model description into geometric description of realistic columns i.e. from the discrete model, we construct isospectral WUCF columns with rectangular cross-sections varying in width and depth. As part of numerical studies to demonstrate efficacy of techniques presented, frequency parameters of a uniform column and three types of tapered CF columns under different combinations of loading parameters are obtained from the discrete model. Critical combinations of these parameters for a typical tapered column are derived. These results match with published results. Example CF columns, under arbitrarily-chosen combinations of loading parameters are considered and for each combination, isospectral WUCF columns are constructed. Role of transformation parameters in determining characteristics of isospectral columns is discussed and optimum values are deduced. Natural frequencies of these WUCF columns computed using Finite Element Method (FEM) match well with those of the given gravity-loaded CF column with tip force, hence confirming isospectrality.

A promising oral fucoidan-based antithrombotic nanosystem: development, activity and safety

NASA Astrophysics Data System (ADS)

da Silva, L. C. R. P.; Todaro, V.; do Carmo, F. A.; Frattani, F. S.; de Sousa, V. P.; Rodrigues, C. R.; Sathler, P. C.; Cabral, L. M.

2018-04-01

Fucoidan-loaded nanoparticles emerge as great candidates for oral anticoagulant therapy, due to increases in the bioavailability and circulation time of this natural anticoagulant. Crosslinks between chitosan chains are performed using glutaraldehyde to confer higher gastric pH resistance to nanoparticle matrices. In this work, chitosan-fucoidan nanoparticles, without (NpCF) and with glutaraldehyde crosslink (NpCF 1% and NpCF 2%), were prepared to evaluate their anticoagulant, antithrombotic and hemorrhagic profiles. Nanoparticles were characterized by average diameter (AD), polydispersity index, zeta potential, Fourier transform infrared spectroscopy and fucoidan in vitro release. Anticoagulant and antithrombotic activities were determined by in vitro and in vivo models, respectively. Hemorrhagic profile was in vivo evaluated by tail bleeding assay. Preparations showed nanometric and homogeneous ADs. Zeta potentials of NpCF and NpCF 1% were stable over the gastrointestinal pH range, which was confirmed by low fucoidan release in gastric and enteric media. In pH 7.4, NpCF and NpCF 1% demonstrated fucoidan release of 65.5% and 60.6%, respectively, within the first 24 h. In comparison to fucoidan, NpCF and NpCF 1% showed increased in vitro anticoagulant activity. A significant difference in the oral antithrombotic profile of NpCF 1% was found in comparison to fucoidan. Bleeding profile of NpCF and NpCF 1% showed no differences to the control group, indicating the safety of these systems. Surprisingly, the oral antithrombotic profile of commercially available fucoidan, from Fucus vesiculosus, has not been previously determined, which reveals new possibilities. In this work, significant advances were observed in the anticoagulant and antithrombotic profiles of fucoidan through the preparation of NpCF 1%.

Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report.

PubMed

Ramsey, Bonnie W; Banks-Schlegel, Susan; Accurso, Frank J; Boucher, Richard C; Cutting, Garry R; Engelhardt, John F; Guggino, William B; Karp, Christopher L; Knowles, Michael R; Kolls, Jay K; LiPuma, John J; Lynch, Susan; McCray, Paul B; Rubenstein, Ronald C; Singh, Pradeep K; Sorscher, Eric; Welsh, Michael

2012-04-15

Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled "Future Research Directions in Early CF Lung Disease" on September 21-22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene-environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease.

An "ex vivo model" contributing to the diagnosis and evaluation of new drugs in cystic fibrosis.

PubMed

Di Lullo, A M; Scorza, M; Amato, F; Comegna, M; Raia, V; Maiuri, L; Ilardi, G; Cantone, E; Castaldo, G; Iengo, M

2017-06-01

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. About 2000 mutations have been described so far. We setup an ex vivo model of human nasal epithelial cells (HNECs) to study CF patients testing the effect of novel mutations and molecular therapies. We performed sampling (by brushing), followed by culture and analysis of HNECs using a series of molecular techniques. We performed 50 brushings from CF patients and controls. Using cultured cells, we: i) demonstrated the widely heterogeneous CFTR expression in patients and in controls; ii) defined the splicing effect of a CFTR mutation; iii) assessed the CFTR gating activity in patients bearing different mutations; iv) demonstrated that butyrate significantly enhances CFTR expression. Based on our data, we can conclude: 1) HNEC brushing is performed without anaesthesia and is well tolerated in all CF patients (children and adults); 2) HNECs can be preserved for up to 48 hours before culture allowings multicentre studies; 3) HNECs culture can be considered a suitable model to study the molecular effects of new CFTR gene mutations and/or uncertain meaning specific mutations of carriers; 4) an ex vivo model of HNECs may be used to evaluate, before human use, the effect of new drugs on patients' cells bearing specific CFTR mutations; 5) the methodology is adequate for a quantitative measurement, by fluorescence, of the CFTR gating activity of the HNECs from patients with different genotypes identifying: a) CF patients bearing two severe mutations with an activity < 10% (compared to controls - 100%); b) CF patients bearing at least a mild mutation with an activity of 10-20%; c) CF carriers (heterozygous subjects) with an activity between 40-70%. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.

The Pathways from a Behavior Change Communication Intervention to Infant and Young Child Feeding in Bangladesh Are Mediated and Potentiated by Maternal Self-Efficacy.

PubMed

Zongrone, Amanda A; Menon, Purnima; Pelto, Gretel H; Habicht, Jean-Pierre; Rasmussen, Kathleen M; Constas, Mark A; Vermeylen, Francoise; Khaled, Adiba; Saha, Kuntal K; Stoltzfus, Rebecca J

2018-02-01

Although self-efficacy is a potential determinant of feeding and care behaviors, there is limited empirical analysis of the role of maternal self-efficacy in low- and middle-income countries. In the context of behavior change interventions (BCIs) addressing complementary feeding (CF), it is possible that maternal self-efficacy can mediate or enhance intervention impacts. In the context of a BCI in Bangladesh, we studied the role of maternal self-efficacy for CF (MSE-CF) for 2 CF behaviors with the use of a theoretically grounded empirical model of determinants to illustrate the potential roles of MSE-CF. We developed and tested a locally relevant scale for MSE-CF and included it in a survey (n = 457 mothers of children aged 6-24 mo) conducted as part of a cluster-randomized evaluation. Qualitative research was used to inform the selection of 2 intervention-targeted behaviors: feeding green leafy vegetables in the last 24 h (GLV) and on-time introduction of egg (EGG) between 6 and 8 mo of age. We then examined direct, mediated, and potentiated paths of MSE-CF in relation to the impacts of the BCI on these behaviors with the use of regression and structural equation modeling. GLV and EGG were higher in the intensive group than in the nonintensive control group (16.0 percentage points for GLV; P < 0.001; 11.2 percentage points for EGG; P = 0.037). For GLV, MSE-CF mediated (β = 0.345, P = 0.010) and potentiated (β = 0.390, P = 0.038) the effect of the intensive group. In contrast, MSE-CF did not mediate or potentiate the effect of the intervention on EGG. MSE-CF was a significant mediator and potentiator for GLV but not for EGG. The divergent findings highlight the complex determinants of individual specific infant and young child feeding behaviors. The study shows the value of measuring behavioral determinants, such as MSE-CF, that affect a caregiver's capability to adopt intervention-targeted behaviors.

Hydrogel-based ultra-moisturizing cream formulation for skin hydration and enhanced dermal drug delivery.

PubMed

Lee, Sang Gon; Kim, Sung Rae; Cho, Hye In; Kang, Mean Hyung; Yeom, Dong Woo; Lee, Seo Hyun; Lee, Sangkil; Choi, Young Wook

2014-01-01

To develop an external vehicle for skin hydration and enhanced dermal drug delivery, a hydrogel-based ultra-moisturizing cream (HUMC) was successfully formulated with carbopol 934P, urea, Tinocare GL, grape seed oil, and other excipients. The HUMC showed plastic flow behavior due to a gel structure with a cream base. Different types of drug-free vehicles such as a hydrogel, conventional cream (CC), and three HUMCs were prepared and subjected to an in vivo skin hydration test on a hairless mouse using a corneometer. Hydration effect (∆AU) was in the order of HUMC2>HUMC1 ≥ CC>HUMC3>hydrogel. Using nile red (NR) and 5-carboxyfluorescein (5-CF) as lipophilic and hydrophilic fluorescent probes, respectively, in vitro skin permeation and accumulation studies were conducted using Franz diffusion cells. The values of steady-state flux (Jss, ng/h/cm(2)) were obtained: 74.8 (CC), 145.6 (HUMC1), and 161.9 (HUMC2) for NR delivery; 6.8 (CC), 8.3 (HUMC1), and 10.9 (HUMC2) for 5-CF delivery. The amounts retained in the skin at 12 h (Qr, ng/cm(2)) were determined: 86.4 (CC) and 102.0 (HUMC2) for NR; and 70.1 (CC) and 195.6 (HUMC2) for 5-CF. Confocal microscopy was used to visualize the distribution of the fluorescent probes. NR tended to be localized into the deeper part of the skin with adipose tissue whereas 5-CF localized in the upper layer of the skin. Thus we propose that HUMC2 is an efficacious vehicle for skin hydration and enhances dermal delivery of lipophilic and hydrophilic drugs.

Multicenter Retrospective Study of Cefmetazole and Flomoxef for Treatment of Extended-Spectrum-β-Lactamase-Producing Escherichia coli Bacteremia

PubMed Central

Yamamoto, Masaki; Nagao, Miki; Komori, Toshiaki; Fujita, Naohisa; Hayashi, Akihiko; Shimizu, Tsunehiro; Watanabe, Harumi; Doi, Shoichi; Tanaka, Michio; Takakura, Shunji; Ichiyama, Satoshi

2015-01-01

The efficacy of cefmetazole and flomoxef (CF) for the treatment of patients with extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) bacteremia (ESBL-CF group) was compared with that of carbapenem treatment for ESBL-EC patients (ESBL-carbapenem group) and with that of CF treatment in patients with non-ESBL-EC bacteremia (non-ESBL-CF group). Adult patients treated for E. coli bacteremia in four hospitals were retrospectively evaluated. The 30-day mortality rates in patients belonging to the ESBL-CF, ESBL-carbapenem, and non-ESBL-CF groups were compared as 2 (empirical and definitive therapy) cohorts. The adjusted hazard ratios (aHRs) for mortality were calculated using Cox regression models with weighting according to the inverse probability of propensity scores for receiving CF or carbapenem treatment. The empirical-therapy cohort included 104 patients (ESBL-CF, 26; ESBL-carbapenem, 45; non-ESBL-CF, 33), and the definitive-therapy cohort included 133 patients (ESBL-CF, 59; ESBL-carbapenem, 54; non-ESBL-CF, 20). The crude 30-day mortality rates for patients in the ESBL-CF, ESBL-carbapenem, and non-ESBL-CF groups were, respectively, 7.7%, 8.9%, and 3.0% in the empirical-therapy cohort and 5.1%, 9.3%, and 5.0% in the definitve-therapy cohort. In patients without hematological malignancy and neutropenia, CF treatment for ESBL-EC patients was not associated with mortality compared with carbapenem treatment (empirical-therapy cohort: aHR, 0.87; 95% confidence interval [CI], 0.11 to 6.52; definitive therapy cohort: aHR, 1.04; CI, 0.24 to 4.49). CF therapy may represent an effective alternative to carbapenem treatment for patients with ESBL-EC bacteremia for empirical and definitive therapy in adult patients who do not have hematological malignancy and neutropenia. PMID:26100708

Multicenter retrospective study of cefmetazole and flomoxef for treatment of extended-spectrum-β-lactamase-producing Escherichia coli bacteremia.

PubMed

Matsumura, Yasufumi; Yamamoto, Masaki; Nagao, Miki; Komori, Toshiaki; Fujita, Naohisa; Hayashi, Akihiko; Shimizu, Tsunehiro; Watanabe, Harumi; Doi, Shoichi; Tanaka, Michio; Takakura, Shunji; Ichiyama, Satoshi

2015-09-01

The efficacy of cefmetazole and flomoxef (CF) for the treatment of patients with extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) bacteremia (ESBL-CF group) was compared with that of carbapenem treatment for ESBL-EC patients (ESBL-carbapenem group) and with that of CF treatment in patients with non-ESBL-EC bacteremia (non-ESBL-CF group). Adult patients treated for E. coli bacteremia in four hospitals were retrospectively evaluated. The 30-day mortality rates in patients belonging to the ESBL-CF, ESBL-carbapenem, and non-ESBL-CF groups were compared as 2 (empirical and definitive therapy) cohorts. The adjusted hazard ratios (aHRs) for mortality were calculated using Cox regression models with weighting according to the inverse probability of propensity scores for receiving CF or carbapenem treatment. The empirical-therapy cohort included 104 patients (ESBL-CF, 26; ESBL-carbapenem, 45; non-ESBL-CF, 33), and the definitive-therapy cohort included 133 patients (ESBL-CF, 59; ESBL-carbapenem, 54; non-ESBL-CF, 20). The crude 30-day mortality rates for patients in the ESBL-CF, ESBL-carbapenem, and non-ESBL-CF groups were, respectively, 7.7%, 8.9%, and 3.0% in the empirical-therapy cohort and 5.1%, 9.3%, and 5.0% in the definitve-therapy cohort. In patients without hematological malignancy and neutropenia, CF treatment for ESBL-EC patients was not associated with mortality compared with carbapenem treatment (empirical-therapy cohort: aHR, 0.87; 95% confidence interval [CI], 0.11 to 6.52; definitive therapy cohort: aHR, 1.04; CI, 0.24 to 4.49). CF therapy may represent an effective alternative to carbapenem treatment for patients with ESBL-EC bacteremia for empirical and definitive therapy in adult patients who do not have hematological malignancy and neutropenia. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Nasal potential difference outcomes support diagnostic decisions in cystic fibrosis.

PubMed

Tridello, Gloria; Menin, Laura; Pintani, Emily; Bergamini, Gabriella; Assael, Baroukh Maurice; Melotti, Paola

2016-09-01

When cystic fibrosis (CF) is suspected Nasal Potential Difference (NPD) measurements are proposed to support controversial diagnosis: we investigated appropriate outcomes at the CF Centre of Verona. NPD were measured in 196 subjects: 50 non-CF, 65 classical CF (the reference group) and 81 with uncertain CF (case group). Discriminating power was determined by comparison between several outcomes from the CF reference group versus non-CF: basal, amiloride, 0Cl, isoproterenol, ATP, Delta-amiloride, Delta-0Cl, Delta-isoproterenol, Delta-ATP, Delta-isoproterenol+Delta-0Cl, Wilschanski Index (WI) and Sermet score (SS). The most appropriate cut-off values for variables with the best discriminating power were then applied to the case group. Descriptive statistics, logistic regression models and ROC curve analysis were applied. WI and SS were the most powerful in discriminating CF from non-CF subjects. In the reference group sensitivity of the 0.82 WI cut-off was 98%, specificity 96%; both sensitivity and specificity of the -0.44 SS cut-off value were 100%. For the case group, WI and SS were, respectively, consistent with CF diagnosis in 94% and 92% of the cases. Formulae have the highest discriminating power and can support the diagnosis in uncertain cases; they should be utilized for standardized interpretation of NPD for diagnosis and possibly for clinical research. Copyright © 2016. Published by Elsevier B.V.

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.

Transcutaneous drug delivery by liposomes using fractional laser technology.

PubMed

Fujimoto, Takahiro; Wang, Jian; Baba, Kazuki; Oki, Yuka; Hiruta, Yuki; Ito, Masayuki; Ito, Shinobu; Kanazawa, Hideko

2017-07-01

Transdermal delivery of hydrophilic peptides remains a challenge due to their poor cellular uptake and transdermal penetration. We hypothesize that combination of a CO 2 fractional laser to enhance percutaneous absorption and liposomes as transdermal carriers would improve skin penetration of hydrophilic drugs. NA. Liposomes were prepared using membrane fusion lipid dioleoylphosphatidylethanolamine, and used to deliver 5-carboxyfluorescein (CF) and fluorescein isothiocyanate-conjugated ovalbumin (OVA-FITC) as model hydrophilic peptide drugs. Liposome size was estimated by dynamic light scattering. Liposome uptake into murine macrophage cells and penetration or permeation into Yucatan micropig skin after irradiation by CO 2 fractional laser at varying energy levels (laser power and exposure duration) were investigated using Franz cell and fluorescence microscopy. Oxidative damage to the irradiated mouse skin was assessed by electron spin resonance. Size of CF and OVA-FITC encapsulated liposomes was 324 ± 75 nm. Cellular uptake of OVA-FITC delivered by liposomes was 10-fold higher (1,370 relative fluorescence units, RFU) than delivered in solution form (130 RFU). Fractional laser irradiation increased skin permeation rate of CF liposomes (0-10%) and OVA-FITC liposomes (4-40%) in a dose-dependent manner. Although peeling off the stratum corneum facilitated CF liposome penetration at low energy levels (2.69-3.29 J/cm 2 ; 10-20 W for 500 μs), drug permeation was similar (7-8%) in peeled or untreated skin at higher laser energy levels (6.06 J/cm 2 ; 20 W for 1,500 μs). FITC penetrated deeper in the skin after laser irradiation. However, OH, O2-, and VC reactive oxygen species were generated upon irradiation of the skin with a fractional CO 2 laser. Increasing laser power and irradiation, time increased liposome uptake by cells and penetration of peptide drugs across the skin in a dose-dependent manner. High-energy CO 2 fractional laser overcomes the rate-limiting barrier function of the stratum corneum. Further investigations are required to establish the safety and efficacy of fractional laser-irradiation assisted delivery of liposome-encapsulated drugs as a transcutaneous drug delivery system. Lasers Surg. Med. 49:525-532, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Biomechanical Analysis of Lateral Lumbar Interbody Fusion Constructs with Various Fixation Options: Based on a Validated Finite Element Model.

PubMed

Zhang, Zhenjun; Fogel, Guy R; Liao, Zhenhua; Sun, Yitao; Liu, Weiqiang

2018-06-01

Lateral lumbar interbody fusion using cage supplemented with fixation has been used widely in the treatment of lumbar disease. A combined fixation (CF) of lateral plate and spinous process plate may provide multiplanar stability similar to that of bilateral pedicle screws (BPS) and may reduce morbidity. The biomechanical influence of the CF on cage subsidence and facet joint stress has not been well described. The aim of this study was to compare biomechanics of various fixation options and to verify biomechanical effects of the CF. The surgical finite element models with various fixation options were constructed based on computed tomography images. The lateral plate and posterior spinous process plate were applied (CF). The 6 motion modes were simulated. Range of motion (ROM), cage stress, endplate stress, and facet joint stress were compared. For the CF model, ROM, cage stress, and endplate stress were the minimum in almost all motion modes. Compared with BPS, the CF reduced ROM, cage stress, and endplate stress in all motion modes. The ROM was reduced by more than 10% in all motion modes except for flexion; cage stress and endplate stress were reduced more than 10% in all motion modes except for rotation-left. After interbody fusion, facet joint stress was reduced substantially compared with the intact conditions in all motion modes except for flexion. The combined plate fixation may offer an alternative to BPS fixation in lateral lumbar interbody fusion. Copyright © 2018 Elsevier Inc. All rights reserved.

A Chimeric protein of CFA/I, CS6 subunits and LTB/STa toxoid protects immunized mice against enterotoxigenic Escherichia coli.

PubMed

Zeinalzadeh, Narges; Salmanian, Ali Hatef; Goujani, Goli; Amani, Jafar; Ahangari, Ghasem; Akhavian, Asal; Jafari, Mahyat

2017-07-01

Enterotoxigenic Escherichia Coli (ETEC) strains are the commonest bacteria causing diarrhea in children in developing countries and travelers to these areas. Colonization factors (CFs) and enterotoxins are the main virulence determinants in ETEC pathogenesis. Heterogeneity of CFs is commonly considered the bottleneck to developing an effective vaccine. It is believed that broad spectrum protection against ETEC would be achieved by induced anti-CF and anti-enterotoxin immunity simultaneously. Here, a fusion antigen strategy was used to construct a quadrivalent recombinant protein called 3CL and composed of CfaB, a structural subunit of CFA/I, and CS6 structural subunits, LTB and STa toxoid of ETEC. Its anti-CF and antitoxin immunogenicity was then assessed. To achieve high-level expression, the 3CL gene was synthesized using E. coli codon bias. Female BALB/C mice were immunized with purified recombinant 3CL. Immunized mice developed antibodies that were capable of detecting each recombinant subunit in addition to native CS6 protein and also protected the mice against ETEC challenge. Moreover, sera from immunized mice also neutralized STa toxin in a suckling mouse assay. These results indicate that 3CL can induce anti-CF and neutralizing antitoxin antibodies along with introducing CFA/I as a platform for epitope insertion. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

A Novel Creep-Fatigue Life Prediction Model for P92 Steel on the Basis of Cyclic Strain Energy Density

NASA Astrophysics Data System (ADS)

Ji, Dongmei; Ren, Jianxing; Zhang, Lai-Chang

2016-11-01

A novel creep-fatigue life prediction model was deduced based on an expression of the strain energy density in this study. In order to obtain the expression of the strain energy density, the load-controlled creep-fatigue (CF) tests of P92 steel at 873 K were carried out. Cyclic strain of P92 steel under CF load was divided into elastic strain, applying and unloading plastic strain, creep strain, and anelastic strain. Analysis of cyclic strain indicates that the damage process of P92 steel under CF load consists of three stages, similar to pure creep. According to the characteristics of the strains above, an expression was defined to describe the strain energy density for each cycle. The strain energy density at stable stage is inversely proportional to the total strain energy density dissipated by P92 steel. However, the total strain energy densities under different test conditions are proportional to the fatigue life. Therefore, the expression of the strain energy density at stable stage was chosen to predict the fatigue life. The CF experimental data on P92 steel were employed to verify the rationality of the novel model. The model obtained from the load-controlled CF test of P92 steel with short holding time could predict the fatigue life of P92 steel with long holding time.

High-resolution spectroscopy and global analysis of CF4 rovibrational bands to model its atmospheric absorption

NASA Astrophysics Data System (ADS)

Carlos, M.; Gruson, O.; Richard, C.; Boudon, V.; Rotger, M.; Thomas, X.; Maul, C.; Sydow, C.; Domanskaya, A.; Georges, R.; Soulard, P.; Pirali, O.; Goubet, M.; Asselin, P.; Huet, T. R.

2017-11-01

CF4, or tetrafluoromethane, is a chemically inert and strongly absorbing greenhouse gas, mainly of anthropogenic origin. In order to monitor and reduce its atmospheric emissions and concentration, it is thus necessary to obtain an accurate model of its infrared absorption. Such models allow opacity calculations for radiative transfer atmospheric models. In the present work, we perform a global analysis (divided into two distinct fitting schemes) of 17 rovibrational bands of CF4. This gives a reliable model of many of its lower rovibrational levels and allows the calculation of the infrared absorption in the strongly absorbing ν3 region (1283 cm-1 / 7.8 μm), including the main hot band, namely ν3 +ν2 -ν2 as well as ν3 +ν1 -ν1 ; we could also extrapolate the ν3 +ν4 -ν4 absorption. This represents almost 92% of the absorption at room temperature in this spectral region. A new accurate value of the C-F bond length is evaluated to re = 1.314860(21) Å. The present results have been used to update the HITRAN, GEISA and TFMeCaSDa (VAMDC) databases.

Reduced absorption and enhanced synthesis of cholesterol in patients with cystic fibrosis: a preliminary study of plasma sterols.

PubMed

Gelzo, Monica; Sica, Concetta; Elce, Ausilia; Dello Russo, Antonio; Iacotucci, Paola; Carnovale, Vincenzo; Raia, Valeria; Salvatore, Donatello; Corso, Gaetano; Castaldo, Giuseppe

2016-09-01

Low cholesterol is typically observed in the plasma of patients with cystic fibrosis (CF) contrasting with the subcellular accumulation of cholesterol demonstrated in CF cells and in mice models. However, the homeostasis of cholesterol has not been well investigated in patients with CF. We studied the plasma of 26 patients with CF and 33 unaffected controls campesterol and β-sitosterol as markers of intestinal absorption and lathosterol as a marker of de novo cholesterol biosynthesis by gas chromatography (GC-FID and GC-MS). Plasma campesterol and β-sitosterol results were significantly (p=0.01) lower while plasma lathosterol was significantly higher (p=0.001) in patients with CF as compared to control subjects. Plasma cholesterol results were significantly lower (p=0.01) in CF patients. Our data suggest that the impaired intestinal absorption of exogenous sterols in patients with CF stimulates the endogenous synthesis of cholesterol, but the levels of total cholesterol in plasma remain lower. This may be due to the CFTR dysfunction that reduces cholesterol blood excretion causing the accumulation of cholesterol in liver cells and in other tissues contributing to trigger CF chronic inflammation.

Endoplasmic Reticulum Protein TXNDC5 Augments Myocardial Fibrosis by Facilitating Extracellular Matrix Protein Folding and Redox-Sensitive Cardiac Fibroblast Activation.

PubMed

Shih, Ying-Chun; Chen, Chao-Ling; Zhang, Yan; Mellor, Rebecca L; Kanter, Evelyn M; Fang, Yun; Wang, Hua-Chi; Hung, Chen-Ting; Nong, Jing-Yi; Chen, Hui-Ju; Lee, Tzu-Han; Tseng, Yi-Shuan; Chen, Chiung-Nien; Wu, Chau-Chung; Lin, Shuei-Liong; Yamada, Kathryn A; Nerbonne, Jeanne M; Yang, Kai-Chien

2018-04-13

Cardiac fibrosis plays a critical role in the pathogenesis of heart failure. Excessive accumulation of extracellular matrix (ECM) resulting from cardiac fibrosis impairs cardiac contractile function and increases arrhythmogenicity. Current treatment options for cardiac fibrosis, however, are limited, and there is a clear need to identify novel mediators of cardiac fibrosis to facilitate the development of better therapeutics. Exploiting coexpression gene network analysis on RNA sequencing data from failing human heart, we identified TXNDC5 (thioredoxin domain containing 5), a cardiac fibroblast (CF)-enriched endoplasmic reticulum protein, as a potential novel mediator of cardiac fibrosis, and we completed experiments to test this hypothesis directly. The objective of this study was to determine the functional role of TXNDC5 in the pathogenesis of cardiac fibrosis. RNA sequencing and Western blot analyses revealed that TXNDC5 mRNA and protein were highly upregulated in failing human left ventricles and in hypertrophied/failing mouse left ventricle. In addition, cardiac TXNDC5 mRNA expression levels were positively correlated with those of transcripts encoding transforming growth factor β1 and ECM proteins in vivo. TXNDC5 mRNA and protein were increased in human CF (hCF) under transforming growth factor β1 stimulation in vitro. Knockdown of TXNDC5 attenuated transforming growth factor β1-induced hCF activation and ECM protein upregulation independent of SMAD3 (SMAD family member 3), whereas increasing expression of TXNDC5 triggered hCF activation and proliferation and increased ECM protein production. Further experiments showed that TXNDC5, a protein disulfide isomerase, facilitated ECM protein folding and that depletion of TXNDC5 led to ECM protein misfolding and degradation in CF. In addition, TXNDC5 promotes hCF activation and proliferation by enhancing c-Jun N-terminal kinase activity via increased reactive oxygen species, derived from NAD(P)H oxidase 4. Transforming growth factor β1-induced TXNDC5 upregulation in hCF was dependent on endoplasmic reticulum stress and activating transcription factor 6-mediated transcriptional control. Targeted disruption of Txndc5 in mice ( Txndc5 -/- ) revealed protective effects against isoproterenol-induced cardiac hypertrophy, reduced fibrosis (by ≈70%), and markedly improved left ventricle function; post-isoproterenol left ventricular ejection fraction was 59.1±1.5 versus 40.1±2.5 ( P <0.001) in Txndc5 -/- versus wild-type mice, respectively. The endoplasmic reticulum protein TXNDC5 promotes cardiac fibrosis by facilitating ECM protein folding and CF activation via redox-sensitive c-Jun N-terminal kinase signaling. Loss of TXNDC5 protects against β agonist-induced cardiac fibrosis and contractile dysfunction. Targeting TXNDC5, therefore, could be a powerful new therapeutic approach to mitigate excessive cardiac fibrosis, thereby improving cardiac function and outcomes in patients with heart failure. © 2018 American Heart Association, Inc.

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

Sawada, Y.; Kawai, R.; McManaway, M.

(3H)Cyclofoxy (CF: 17-cyclopropylmethyl-3,14-dihydroxy-4,5-alpha-epoxy-6-beta-fluoromorp hinan) is an opioid antagonist with affinity to both mu and kappa subtypes that was synthesized for quantitative evaluation of opioid receptor binding in vivo. Two sets of experiments in rats were analyzed. The first involved determining the metabolite-corrected blood concentration and tissue distribution of CF in brain 1 to 60 min after i.v. bolus injection. The second involved measuring brain washout for 15 to 120 s following intracarotid artery injection of CF. A physiologically based model and a classical compartmental pharmacokinetic model were compared. The models included different assumptions for transport across the blood-brain barrier (BBB);more » estimates of nonspecific tissue binding and specific binding to a single opiate receptor site were found to be essentially the same with both models. The nonspecific binding equilibrium constant varied modestly in different brain structures (Keq = 3-9), whereas the binding potential (BP) varied over a much broader range (BP = 0.6-32). In vivo estimates of the opioid receptor dissociation constant were similar for different brain structures (KD = 2.1-5.2 nM), whereas the apparent receptor density (Bmax) varied between 1 (cerebellum) and 78 (thalamus) pmol/g of brain. The receptor dissociation rate constants in cerebrum (k4 = 0.08-0.16 min-1; koff = 0.16-0.23 min-1) and brain vascular permeability (PS = 1.3-3.4 ml/min/g) are sufficiently high to achieve equilibrium conditions within a reasonable period of time. Graphical analysis of the data is inappropriate due to the high tissue-loss rate constant for CF in brain. From these findings, CF should be a very useful opioid receptor ligand for the estimation of the receptor binding parameters in human subjects using (18F)CF and positron emission tomography.« less

The Tumor Necrosis Factor α (-308 A/G) Polymorphism Is Associated with Cystic Fibrosis in Mexican Patients

PubMed Central

Sanchez-Dominguez, Celia N.; Reyes-Lopez, Miguel A.; Bustamante, Adriana; Cerda-Flores, Ricardo M.; Villalobos-Torres, Maria del C.; Gallardo-Blanco, Hugo L.; Rojas-Martinez, Augusto; Martinez-Rodriguez, Herminia G.; Barrera-Saldaña, Hugo A.; Ortiz-Lopez, Rocio

2014-01-01

Environmental and genetic factors may modify or contribute to the phenotypic differences observed in multigenic and monogenic diseases, such as cystic fibrosis (CF). An analysis of modifier genes can be helpful for estimating patient prognosis and directing preventive care. The aim of this study is to determine the association between seven genetic variants of four modifier genes and CF by comparing their corresponding allelic and genotypic frequencies in CF patients (n = 81) and control subjects (n = 104). Genetic variants of MBL2 exon 1 (A, B, C and D), the IL-8 promoter (−251 A/T), the TNFα promoter (TNF1/TNF2), and SERPINA1 (PI*Z and PI*S) were tested in CF patients and control subjects from northeastern Mexico by PCR-RFLP. Results The TNF2 allele (P = 0.012, OR 3.43, 95% CI 1.25–9.38) was significantly associated with CF under the dominant and additive models but was not associated with CF under the recessive model. This association remained statistically significant after adjusting for multiple tests using the Bonferroni correction (P = 0.0482). The other tested variants and genotypes did not show any association with the disease. Conclusion An analysis of seven genetic variants of four modifier genes showed that one variant, the TNF2 allele, appears to be significantly associated with CF in Mexican patients. PMID:24603877

The HDAC inhibitor SAHA does not rescue CFTR membrane expression in Cystic Fibrosis.

PubMed

Bergougnoux, Anne; Petit, Aurélie; Knabe, Lucie; Bribes, Estelle; Chiron, Raphaël; De Sario, Albertina; Claustres, Mireille; Molinari, Nicolas; Vachier, Isabelle; Taulan-Cadars, Magali; Bourdin, Arnaud

2017-07-01

The development of suitable Cystic Fibrosis (CF) models for preclinical bench tests of therapeutic candidates is challenging. Indeed, the validation of molecules to rescue the p.Phe508del-CFTR channel (encoded by the Cystic Fibrosis Transmembrane conductance Regulator gene carrying the p.Phe508del mutation) requires taking into account their overall effects on the epithelium. Suberoylanilide Hydroxamic Acid (SAHA), a histone deacetylase inhibitor (HDACi), was previously shown to be a CFTR corrector via proteostasis modulation in CFTR-deficient immortalized cells. Here, we tested SAHA effects on goblet cell metaplasia using an ex vivo model based on the air-liquid interface (ALI) culture of differentiated airway epithelial cells obtained by nasal scraping from CF patients and healthy controls. Ex vivo epithelium grew successfully in ALI cultures with significant rise in the expression of CFTR and of markers of airway epithelial differentiation compared to monolayer cell culture. SAHA decreased CFTR transcript and protein levels in CF and non-CF epithelia. Whereas SAHA induced lysine hyperacetylation, it did not change histone modifications at the CFTR promoter. SAHA reduced MUC5AC and MUC5B expression and inhibited goblet epithelial cell differentiation. Similar effects were obtained in CF and non-CF epithelia. All the effects were fully reversible within five days from SAHA withdrawal. We conclude that, ex vivo, SAHA modulate the structure of airway epithelia without specific effect on CFTR gene and protein suggesting that HDACi cannot be useful for CF treatment. Copyright © 2017. Published by Elsevier Ltd.

Forecasting the Long-Term Clinical and Economic Outcomes of Lumacaftor/Ivacaftor in Cystic Fibrosis Patients with Homozygous phe508del Mutation.

PubMed

Dilokthornsakul, Piyameth; Patidar, Mausam; Campbell, Jonathan D

2017-12-01

To forecast lifetime outcomes and cost of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis (CF) with homozygous phe508del mutation from the US payer perspective. A lifetime Markov model was developed from a US payer perspective. The model included five health states: 1) mild lung disease (percent predicted forced expiratory volume in 1 second [FEV 1 ] >70%), 2) moderate lung disease (40% ≤ FEV 1 ≤ 70%), 3) severe lung disease (FEV 1 < 40%), 4) lung transplantation, and 5) death. All inputs were derived from published literature. We estimated lumacaftor/ivacaftor's improvement in outcomes compared with a non-CF referent population as well as CF-specific mortality estimates. Lumacaftor/ivacaftor was associated with additional 2.91 life-years (95% credible interval 2.55-3.56) and additional 2.42 quality-adjusted life-years (QALYs) (95% credible interval 2.10-2.98). Lumacaftor/ivacaftor was associated with improvements in survival and QALYs equivalent to 27.6% and 20.7%, respectively, for the survival and QALY gaps between CF usual care and their non-CF peers. The incremental lifetime cost was $2,632,249. Lumacaftor/ivacaftor increased life-years and QALYs in CF patients with the homozygous phe508del mutation and moved morbidity and mortality closer to that of their non-CF peers but it came with higher cost. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Blocking phosphatidylcholine utilization in Pseudomonas aeruginosa, via mutagenesis of fatty acid, glycerol and choline degradation pathways, confirms the importance of this nutrient source in vivo.

PubMed

Sun, Zhenxin; Kang, Yun; Norris, Michael H; Troyer, Ryan M; Son, Mike S; Schweizer, Herbert P; Dow, Steven W; Hoang, Tung T

2014-01-01

Pseudomonas aeruginosa can grow to very high-cell-density (HCD) during infection of the cystic fibrosis (CF) lung. Phosphatidylcholine (PC), the major component of lung surfactant, has been hypothesized to support HCD growth of P. aeruginosa in vivo. The phosphorylcholine headgroup, a glycerol molecule, and two long-chain fatty acids (FAs) are released by enzymatic cleavage of PC by bacterial phospholipase C and lipases. Three different bacterial pathways, the choline, glycerol, and fatty acid degradation pathways, are then involved in the degradation of these PC components. Here, we identified five potential FA degradation (Fad) related fadBA-operons (fadBA1-5, each encoding 3-hydroxyacyl-CoA dehydrogenase and acyl-CoA thiolase). Through mutagenesis and growth analyses, we showed that three (fadBA145) of the five fadBA-operons are dominant in medium-chain and long-chain Fad. The triple fadBA145 mutant also showed reduced ability to degrade PC in vitro. We have previously shown that by partially blocking Fad, via mutagenesis of fadBA5 and fadDs, we could significantly reduce the ability of P. aeruginosa to replicate on FA and PC in vitro, as well as in the mouse lung. However, no studies have assessed the ability of mutants, defective in choline and/or glycerol degradation in conjunction with Fad, to grow on PC or in vivo. Hence, we constructed additional mutants (ΔfadBA145ΔglpD, ΔfadBA145ΔbetAB, and ΔfadBA145ΔbetABΔglpD) significantly defective in the ability to degrade FA, choline, and glycerol and, therefore, PC. The analysis of these mutants in the BALB/c mouse lung infection model showed significant inability to utilize PC in vitro, resulted in decreased replication fitness and competitiveness in vivo compared to the complement strain, although there was little to no variation in typical virulence factor production (e.g., hemolysin, lipase, and protease levels). This further supports the hypothesis that lung surfactant PC serves as an important nutrient for P. aeruginosa during CF lung infection.

Compassion Fatigue and Psychological Distress Among Social Workers: A Validation Study

PubMed Central

Adams, Richard E.; Boscarino, Joseph A.; Figley, Charles R.

2009-01-01

Few studies have focused on caring professionals and their emotional exhaustion from working with traumatized clients, referred to as compassion fatigue (CF). The present study had 2 goals: (a) to assess the psychometric properties of a CF scale, and (b) to examine the scale's predictive validity in a multivariate model. The data came from a survey of social workers living in New York City following the September 11, 2001, terrorist attacks on the World Trade Center. Factor analyses indicated that the CF scale measured multiple dimensions. After overlapping items were eliminated, the scale measured 2 key underlying dimensions—secondary trauma and job burnout. In a multivariate model, these dimensions were related to psychological distress, even after other risk factors were controlled. The authors discuss the results in light of increasing the ability of professional caregivers to meet the emotional needs of their clients within a stressful environment without experiencing CF. PMID:16569133

Additive Manufacturing of PLA and CF/PLA Binding Layer Specimens via Fused Deposition Modeling

NASA Astrophysics Data System (ADS)

Li, Yuhang; Gao, Shiyou; Dong, Rongmei; Ding, Xuebing; Duan, Xiaoxi

2018-02-01

As one of the most popular additive manufacturing techniques, fused deposition modeling (FDM) is successfully applied in aerospace, automotive, architecture, and other fields to fabricate thermoplastic parts. Unfortunately, as a result of the limited nature of the mechanical properties and mass in raw materials, there is a pressing need to improve mechanical properties and reduce weight for FDM parts. Therefore, this paper presents an experiment of a special polylactic acid (PLA) and carbon fiber (CF)/PLA-laminated experimental specimen fabricated using the FDM process. The mechanical properties and mass analysis of the new composites for the PLA and CF/PLA binding layer specimen are investigated experimentally. Through the experimental analysis, one can conclude that the mass of laminated specimen is lighter than the CF/PLA specimen, and the tensile and flexural mechanical properties are higher than the pure PLA specimen.

Genetically and Phenotypically Distinct Pseudomonas aeruginosa Cystic Fibrosis Isolates Share a Core Proteomic Signature

PubMed Central

Penesyan, Anahit; Kumar, Sheemal S.; Kamath, Karthik; Shathili, Abdulrahman M.; Venkatakrishnan, Vignesh; Krisp, Christoph; Packer, Nicolle H.; Molloy, Mark P.; Paulsen, Ian T.

2015-01-01

The opportunistic pathogen Pseudomonas aeruginosa is among the main colonizers of the lungs of cystic fibrosis (CF) patients. We have isolated and sequenced several P. aeruginosa isolates from the sputum of CF patients and compared them with each other and with the model strain PAO1. Phenotypic analysis of CF isolates showed significant variability in colonization and virulence-related traits suggesting different strategies for adaptation to the CF lung. Genomic analysis indicated these strains shared a large set of core genes with the standard laboratory strain PAO1, and identified the genetic basis for some of the observed phenotypic differences. Proteomics revealed that in a conventional laboratory medium PAO1 expressed 827 proteins that were absent in the CF isolates while the CF isolates shared a distinctive signature set of 703 proteins not detected in PAO1. PAO1 expressed many transporters for the uptake of organic nutrients and relatively few biosynthetic pathways. Conversely, the CF isolates expressed a narrower range of transporters and a broader set of metabolic pathways for the biosynthesis of amino acids, carbohydrates, nucleotides and polyamines. The proteomic data suggests that in a common laboratory medium PAO1 may transport a diverse set of “ready-made” nutrients from the rich medium, whereas the CF isolates may only utilize a limited number of nutrients from the medium relying mainly on their own metabolism for synthesis of essential nutrients. These variations indicate significant differences between the metabolism and physiology of P. aeruginosa CF isolates and PAO1 that cannot be detected at the genome level alone. The widening gap between the increasing genomic data and the lack of phenotypic data means that researchers are increasingly reliant on extrapolating from genomic comparisons using experimentally characterized model organisms such as PAO1. While comparative genomics can provide valuable information, our data suggests that such extrapolations may be fraught with peril. PMID:26431321

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

Advances in Cell and Gene-based Therapies for Cystic Fibrosis Lung Disease

PubMed Central

Oakland, Mayumi; Sinn, Patrick L; McCray Jr, Paul B

2012-01-01

Cystic fibrosis (CF) is a disease characterized by airway infection, inflammation, remodeling, and obstruction that gradually destroy the lungs. Direct delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelia may offer advantages, as the tissue is accessible for topical delivery of vectors. Yet, physical and host immune barriers in the lung present challenges for successful gene transfer to the respiratory tract. Advances in gene transfer approaches, tissue engineering, and novel animal models are generating excitement within the CF research field. This review discusses current challenges and advancements in viral and nonviral vectors, cell-based therapies, and CF animal models. PMID:22371844

Chlorophyll Fluorescence Is a Better Proxy for Sunlit Leaf Than Total Canopy Photosynthesis

NASA Astrophysics Data System (ADS)

Chen, J. M.; Wang, Z.; Zhang, F.; Mo, G.

2015-12-01

Chlorophyll fluorescence (CF) results from non-photochemical quenching during plant photosynthesis under excessive radiation. We explore the relationship between gross primary productivity (GPP) and CF using a process ecosystem model, which separates a vegetation canopy into sunlit and shaded leaf groups and simulates the total canopy GPP as the sum of sunlit and shaded leaf GPP. Using GOME-2 and GOSAT data acquired in 2010 over the global land surface, we found that measured CF signals gridded in 1 degree resolution are well correlated with simulated total GPP and its sunlit and shaded components, but the correlation coefficients (R) are largest for the sunlit GPP and smallest for shaded GPP. The seasonal R2 values vary from 0.57 to 0.74, 0.58 to 0.71, and 0.48 to 0.56 for sunlit, total and shaded GPP, respectively. The significance levels for these correlations are all greater than p<0.01. Averaged over the globe, the total simulated shaded GPP is 39% of the total GPP. Theoretically, CF from vegetation comes mostly from sunlit leaves. The significant correlation between measured canopy-level CF and the shaded GPP is likely due to the correlation between shaded and sunlit GPP as both increase with leaf area index. Our simulation confirms the validity of using canopy-level CF measurements to assess the total GPP as the first approximation, although these measurements are a consistently better indicator of sunlit GPP than total GPP. In previous studies, the R2 values for the correlation between CF and total GPP were found to range from 0.76 to 0.88, 0.56 to 0.78, and 0.57 to 0.77 for MPI-BGC, MODIS and CASA model results, respectively. These values are similar or larger than those for sunlit GPP simulated in our study, but are considerably larger than those for total GPP in our study because the correlation for total GPP is contaminated by the inclusion of shaded GPP. All these three models use canopy total light use efficiency without considering the differences between sunlit and shaded leaves, and therefore they mostly capture spatio-temporal variations in sunlit GPP. We therefore argue that solar-induced CF measured from vegetation is a better proxy of sunlit GPP than the total GPP, and the use of CF data for assessing the terrestrial carbon cycle can be improved when sunlit and shaded GPP are modelled separately.

To the non-local theory of cold nuclear fusion.

PubMed

Alexeev, Boris V

2014-10-01

In this paper, we revisit the cold fusion (CF) phenomenon using the generalized Bolzmann kinetics theory which can represent the non-local physics of this CF phenomenon. This approach can identify the conditions when the CF can take place as the soliton creation under the influence of the intensive sound waves. The vast mathematical modelling leads to affirmation that all parts of soliton move with the same velocity and with the small internal change of the pressure. The zone of the high density is shaped on the soliton's front. It means that the regime of the 'acoustic CF' could be realized from the position of the non-local hydrodynamics.

Frontline Science: Pathological conditioning of human neutrophils recruited to the airway milieu in cystic fibrosis.

PubMed

Forrest, Osric A; Ingersoll, Sarah A; Preininger, Marcela K; Laval, Julie; Limoli, Dominique H; Brown, Milton R; Lee, Frances E; Bedi, Brahmchetna; Sadikot, Ruxana T; Goldberg, Joanna B; Tangpricha, Vin; Gaggar, Amit; Tirouvanziam, Rabindra

2018-05-09

Recruitment of neutrophils to the airways, and their pathological conditioning therein, drive tissue damage and coincide with the loss of lung function in patients with cystic fibrosis (CF). So far, these key processes have not been adequately recapitulated in models, hampering drug development. Here, we hypothesized that the migration of naïve blood neutrophils into CF airway fluid in vitro would induce similar functional adaptation to that observed in vivo, and provide a model to identify new therapies. We used multiple platforms (flow cytometry, bacteria-killing, and metabolic assays) to characterize functional properties of blood neutrophils recruited in a transepithelial migration model using airway milieu from CF subjects as an apical chemoattractant. Similarly to neutrophils recruited to CF airways in vivo, neutrophils migrated into CF airway milieu in vitro display depressed phagocytic receptor expression and bacterial killing, but enhanced granule release, immunoregulatory function (arginase-1 activation), and metabolic activities, including high Glut1 expression, glycolysis, and oxidant production. We also identify enhanced pinocytic activity as a novel feature of these cells. In vitro treatment with the leukotriene pathway inhibitor acebilustat reduces the number of transmigrating neutrophils, while the metabolic modulator metformin decreases metabolism and oxidant production, but fails to restore bacterial killing. Interestingly, we describe similar pathological conditioning of neutrophils in other inflammatory airway diseases. We successfully tested the hypothesis that recruitment of neutrophils into airway milieu from patients with CF in vitro induces similar pathological conditioning to that observed in vivo, opening new avenues for targeted therapeutic intervention. ©2018 Society for Leukocyte Biology.

Interactions Between Stress and Sex in Microbial Responses Within the Microbiota-Gut-Brain Axis in a Mouse Model.

PubMed

Tsilimigras, Matthew C B; Gharaibeh, Raad Z; Sioda, Michael; Gray, Laura; Fodor, Anthony A; Lyte, Mark

2018-05-01

Animal models are frequently used to examine stress response, but experiments seldom include females. The connection between the microbiota-gut-brain axis and behavioral stress response is investigated here using a mixed-sex mouse cohort. CF-1 mice underwent alternating days of restraint and forced swim for 19 days (male n = 8, female n = 8) with matching numbers of control animals at which point the 16S rRNA genes of gut microbiota were sequenced. Mixed linear models accounting for stress status and sex with individuals nested in cage to control for cage effects evaluated these data. Murine behaviors in elevated plus-maze, open-field, and light/dark box were investigated. Community-level associations with sex, stress, and their interaction were significant. Males had higher microbial diversity than females (p = .025). Of the 638 operational taxonomic units detected in at least 25% of samples, 94 operational taxonomic units were significant: 31 (stress), 61 (sex), and 34 (sex-stress interaction). Twenty of the 39 behavioral measures were significant for stress, 3 for sex, and 6 for sex-stress. However, no significant associations between behavioral measures and specific microbes were detected. These data suggest sex influences stress response and the microbiota-gut-brain axis and that studies of behavior and the microbiome therefore benefit from consideration of how sex differences drive behavior and microbial community structure. Host stress resilience and absence of associations between stress-induced behaviors with specific microbes suggests that hypothalamic-pituitary-adrenal axis activation represents a threshold for microbial influence on host behavior. Future studies are needed in examining the intersection of sex, stress response, and the microbiota-gut-brain axis.

Effect of dairy farming system, herd, season, parity, and days in milk on modeling of the coagulation, curd firming, and syneresis of bovine milk.

PubMed

Bittante, G; Cipolat-Gotet, C; Malchiodi, F; Sturaro, E; Tagliapietra, F; Schiavon, S; Cecchinato, A

2015-04-01

The objectives of this study were to characterize the variation in curd firmness model parameters obtained from coagulating bovine milk samples, and to investigate the effects of the dairy system, season, individual farm, and factors related to individual cows (days in milk and parity). Individual milk samples (n = 1,264) were collected during the evening milking of 85 farms representing different environments and farming systems in the northeastern Italian Alps. The dairy herds were classified into 4 farming system categories: traditional system with tied animals (29 herds), modern dairy systems with traditional feeding based on hay and compound feed (30 herds), modern dairy system with total mixed ration (TMR) that included silage as a large proportion of the diet (9 herds), and modern dairy system with silage-free TMR (17 herds). Milk samples were analyzed for milk composition and coagulation properties, and parameters were modeled using curd firmness measures (CFt) collected every 15 s from a lacto-dynamographic analysis of 90 min. When compared with traditional milk coagulation properties (MCP), the curd firming measures showed greater variability and yielded a more accurate description of the milk coagulation process: the model converged for 93.1% of the milk samples, allowing estimation of 4 CFt parameters and 2 derived traits [maximum CF (CF(max)) and time from rennet addition to CF(max) (t(max))] for each sample. The milk samples whose CFt equations did not converge showed longer rennet coagulation times obtained from the model (RCT(eq)) and higher somatic cell score, and came from less-productive cows. Among the sources of variation tested for the CFt parameters, dairy herd system yielded the greatest differences for the contrast between the traditional farm and the 3 modern farms, with the latter showing earlier coagulation and greater instant syneresis rate constant (k(SR)). The use of TMR yielded a greater tmax because of a higher instant curd-firming rate constant (k(CF)). Season of sampling was found to be very important, yielding higher values during winter for all traits except k(CF) and k(SR). All CFt traits were affected by individual cow factors. For parity, milk produced by first-lactation cows showed higher k(CF) and k(SR), but delays in achieving CF(max). With respect to stage of lactation, RCT(eq) and potential asymptotic CF increased during the middle of lactation and stabilized thereafter, whereas the 2 instant rate constants presented the opposite pattern, with the lowest (k(CF)) and highest (k(SR)) values occurring in mid lactation. The new challenge offered by prolonging the test interval and individual modeling of milk technological properties allowed us to study the effects of parameters related to the environment and to individual cows. This novel strategy may be useful for investigating the genetic variability of these new coagulation traits. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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.

[Primary branch size of Pinus koraiensis plantation: a prediction based on linear mixed effect model].

PubMed

Dong, Ling-Bo; Liu, Zhao-Gang; Li, Feng-Ri; Jiang, Li-Chun

2013-09-01

By using the branch analysis data of 955 standard branches from 60 sampled trees in 12 sampling plots of Pinus koraiensis plantation in Mengjiagang Forest Farm in Heilongjiang Province of Northeast China, and based on the linear mixed-effect model theory and methods, the models for predicting branch variables, including primary branch diameter, length, and angle, were developed. Considering tree effect, the MIXED module of SAS software was used to fit the prediction models. The results indicated that the fitting precision of the models could be improved by choosing appropriate random-effect parameters and variance-covariance structure. Then, the correlation structures including complex symmetry structure (CS), first-order autoregressive structure [AR(1)], and first-order autoregressive and moving average structure [ARMA(1,1)] were added to the optimal branch size mixed-effect model. The AR(1) improved the fitting precision of branch diameter and length mixed-effect model significantly, but all the three structures didn't improve the precision of branch angle mixed-effect model. In order to describe the heteroscedasticity during building mixed-effect model, the CF1 and CF2 functions were added to the branch mixed-effect model. CF1 function improved the fitting effect of branch angle mixed model significantly, whereas CF2 function improved the fitting effect of branch diameter and length mixed model significantly. Model validation confirmed that the mixed-effect model could improve the precision of prediction, as compare to the traditional regression model for the branch size prediction of Pinus koraiensis plantation.

Spatial Resolution Effects of Digital Terrain Models on Landslide Susceptibility Analysis

NASA Astrophysics Data System (ADS)

Chang, K. T.; Dou, J.; Chang, Y.; Kuo, C. P.; Xu, K. M.; Liu, J. K.

2016-06-01

The purposes of this study are to identify the maximum number of correlated factors for landslide susceptibility mapping and to evaluate landslide susceptibility at Sihjhong river catchment in the southern Taiwan, integrating two techniques, namely certainty factor (CF) and artificial neural network (ANN). The landslide inventory data of the Central Geological Survey (CGS, MOEA) in 2004-2014 and two digital elevation model (DEM) datasets including a 5-meter LiDAR DEM and a 30-meter Aster DEM were prepared. We collected thirteen possible landslide-conditioning factors. Considering the multi-collinearity and factor redundancy, we applied the CF approach to optimize these thirteen conditioning factors. We hypothesize that if the CF values of the thematic factor layers are positive, it implies that these conditioning factors have a positive relationship with the landslide occurrence. Therefore, based on this assumption and positive CF values, seven conditioning factors including slope angle, slope aspect, elevation, terrain roughness index (TRI), terrain position index (TPI), total curvature, and lithology have been selected for further analysis. The results showed that the optimized-factors model provides a better accuracy for predicting landslide susceptibility in the study area. In conclusion, the optimized-factors model is suggested for selecting relative factors of landslide occurrence.

Cystic Fibrosis Colorectal Cancer Screening Consensus Recommendations.

PubMed

Hadjiliadis, Denis; Khoruts, Alexander; Zauber, Ann G; Hempstead, Sarah E; Maisonneuve, Patrick; Lowenfels, Albert B

2018-02-01

Improved therapy has substantially increased survival of persons with cystic fibrosis (CF). But the risk of colorectal cancer (CRC) in adults with CF is 5-10 times greater compared to the general population, and 25-30 times greater in CF patients after an organ transplantation. To address this risk, the CF Foundation convened a multi-stakeholder task force to develop CRC screening recommendations. The 18-member task force consisted of experts including pulmonologists, gastroenterologists, a social worker, nurse coordinator, surgeon, epidemiologist, statistician, CF adult, and a parent. The committee comprised 3 workgroups: Cancer Risk, Transplant, and Procedure and Preparation. A guidelines specialist at the CF Foundation conducted an evidence synthesis February-March 2016 based on PubMed literature searches. Task force members conducted additional independent searches. A total of 1159 articles were retrieved. After initial screening, the committee read 198 articles in full and analyzed 123 articles to develop recommendation statements. An independent decision analysis evaluating the benefits of screening relative to harms and resources required was conducted by the Department of Public Health at Erasmus Medical Center, Netherlands using the Microsimulation Screening Analysis model from the Cancer Innervation and Surveillance Modeling Network. The task force included recommendation statements in the final guideline only if they reached an 80% acceptance threshold. The task force makes 10 CRC screening recommendations that emphasize shared, individualized decision-making and familiarity with CF-specific gastrointestinal challenges. We recommend colonoscopy as the preferred screening method, initiation of screening at age 40 years, 5-year re-screening and 3-year surveillance intervals (unless shorter interval is indicated by individual findings), and a CF-specific intensive bowel preparation. Organ transplant recipients with CF should initiate CRC screening at age 30 years within 2 years of the transplantation because of the additional risk for colon cancer associated with immunosuppression. These recommendations aim to help CF adults, families, primary care physicians, gastroenterologists, and CF and transplantation centers address the issue of CRC screening. They differ from guidelines developed for the general population with respect to the recommended age of screening initiation, screening method, preparation, and the interval for repeat screening and surveillance. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA.

PubMed

Al-Turkmani, M Rabie; Andersson, Charlotte; Alturkmani, Ragheed; Katrangi, Waddah; Cluette-Brown, Joanne E; Freedman, Steven D; Laposata, Michael

2008-09-01

Specific fatty acid alterations have been described in the blood and tissues of cystic fibrosis (CF) patients. The principal alterations include decreased levels of linoleic acid (LA) and docosahexaenoic acid (DHA). We investigated the potential mechanisms of these alterations by studying the cellular uptake of LA and DHA, their distribution among lipid classes, and the metabolism of LA in a human bronchial epithelial cell model of CF. CF (antisense) cells demonstrated decreased levels of LA and DHA compared with wild type (WT, sense) cells expressing normal CFTR. Cellular uptake of LA and DHA was higher in CF cells compared with WT cells at 1 h and 4 h. Subsequent incorporation of LA and DHA into most lipid classes and individual phospholipids was also increased in CF cells. The metabolic conversion of LA to n-6 metabolites, including 18:3n-6 and arachidonic acid, was upregulated in CF cells, indicating increased flux through the n-6 pathway. Supplementing CF cells with DHA inhibited the production of LA metabolites and corrected the n-6 fatty acid defect. In conclusion, the evidence suggests that low LA level in cultured CF cells is due to its increased metabolism, and this increased LA metabolism is corrected by DHA supplementation.

Psychometric evaluation of an item bank for computerized adaptive testing of the EORTC QLQ-C30 cognitive functioning dimension in cancer patients.

PubMed

Dirven, Linda; Groenvold, Mogens; Taphoorn, Martin J B; Conroy, Thierry; Tomaszewski, Krzysztof A; Young, Teresa; Petersen, Morten Aa

2017-11-01

The European Organisation of Research and Treatment of Cancer (EORTC) Quality of Life Group is developing computerized adaptive testing (CAT) versions of all EORTC Quality of Life Questionnaire (QLQ-C30) scales with the aim to enhance measurement precision. Here we present the results on the field-testing and psychometric evaluation of the item bank for cognitive functioning (CF). In previous phases (I-III), 44 candidate items were developed measuring CF in cancer patients. In phase IV, these items were psychometrically evaluated in a large sample of international cancer patients. This evaluation included an assessment of dimensionality, fit to the item response theory (IRT) model, differential item functioning (DIF), and measurement properties. A total of 1030 cancer patients completed the 44 candidate items on CF. Of these, 34 items could be included in a unidimensional IRT model, showing an acceptable fit. Although several items showed DIF, these had a negligible impact on CF estimation. Measurement precision of the item bank was much higher than the two original QLQ-C30 CF items alone, across the whole continuum. Moreover, CAT measurement may on average reduce study sample sizes with about 35-40% compared to the original QLQ-C30 CF scale, without loss of power. A CF item bank for CAT measurement consisting of 34 items was established, applicable to various cancer patients across countries. This CAT measurement system will facilitate precise and efficient assessment of HRQOL of cancer patients, without loss of comparability of results.

Cystic Fibrosis and Its Management Through Established and Emerging Therapies.

PubMed

Spielberg, David R; Clancy, John P

2016-08-31

Cystic fibrosis (CF) is the most common life-shortening autosomal recessive disorder in the Caucasian population and occurs in many other ethnicities worldwide. The daily treatment burden is substantial for CF patients even when they are well, with numerous pharmacologic and physical therapies targeting lung disease requiring the greatest time commitment. CF treatments continue to advance with greater understanding of factors influencing long-term morbidity and mortality. In recent years, in-depth understanding of genetic and protein structure-function relationships has led to the introduction of targeted therapies for patients with specific CF genotypes. With these advances, CF has become a model of personalized or precision medicine. The near future will see greater access to targeted therapies for most patients carrying common mutations, which will mandate individualized bench-to-bedside methodologies for those with rare genotypes.

Detection of Cystic Fibrosis Serological Biomarkers Using a T7 Phage Display Library.

PubMed

Talwar, Harvinder; Hanoudi, Samer Najeeb; Geamanu, Andreea; Kissner, Dana; Draghici, Sorin; Samavati, Lobelia

2017-12-18

Cystic fibrosis (CF) is an autosomal recessive disorder affecting the cystic fibrosis transmembrane conductance regulator (CFTR). CF is characterized by repeated lung infections leading to respiratory failure. Using a high-throughput method, we developed a T7 phage display cDNA library derived from mRNA isolated from bronchoalveolar lavage (BAL) cells and leukocytes of sarcoidosis patients. This library was biopanned to obtain 1070 potential antigens. A microarray platform was constructed and immunoscreened with sera from healthy (n = 49), lung cancer (LC) (n = 31) and CF (n = 31) subjects. We built 1,000 naïve Bayes models on the training sets. We selected the top 20 frequently significant clones ranked with student t-test discriminating CF antigens from healthy controls and LC at a False Discovery Rate (FDR) < 0.01. The performances of the models were validated on an independent validation set. The mean of the area under the receiver operating characteristic (ROC) curve for the classifiers was 0.973 with a sensitivity of 0.999 and specificity of 0.959. Finally, we identified CF specific clones that correlate highly with sweat chloride test, BMI, and FEV1% predicted values. For the first time, we show that CF specific serological biomarkers can be identified through immunocreenings of a T7 phage display library with high accuracy, which may have utility in development of molecular therapy.

Bioelectric characterization of epithelia from neonatal CFTR knockout ferrets.

PubMed

Fisher, John T; Tyler, Scott R; Zhang, Yulong; Lee, Ben J; Liu, Xiaoming; Sun, Xingshen; Sui, Hongshu; Liang, Bo; Luo, Meihui; Xie, Weiliang; Yi, Yaling; Zhou, Weihong; Song, Yi; Keiser, Nicholas; Wang, Kai; de Jonge, Hugo R; Engelhardt, John F

2013-11-01

Cystic fibrosis (CF) is a life-shortening, recessive, multiorgan genetic disorder caused by the loss of CF transmembrane conductance regulator (CFTR) chloride channel function found in many types of epithelia. Animal models that recapitulate the human disease phenotype are critical to understanding pathophysiology in CF and developing therapies. CFTR knockout ferrets manifest many of the phenotypes observed in the human disease, including lung infections, pancreatic disease and diabetes, liver disease, malnutrition, and meconium ileus. In the present study, we have characterized abnormalities in the bioelectric properties of the trachea, stomach, intestine, and gallbladder of newborn CF ferrets. Short-circuit current (ISC) analysis of CF and wild-type (WT) tracheas revealed the following similarities and differences: (1) amiloride-sensitive sodium currents were similar between genotypes; (2) responses to 4,4'-diisothiocyano-2,2'-stilbene disulphonic acid were 3.3-fold greater in CF animals, suggesting elevated baseline chloride transport through non-CFTR channels in a subset of CF animals; and (3) a lack of 3-isobutyl-1-methylxanthine (IBMX)/forskolin-stimulated and N-(2-Naphthalenyl)-((3,5-dibromo-2,4-dihydroxyphenyl)methylene)glycine hydrazide (GlyH-101)-inhibited currents in CF animals due to the lack of CFTR. CFTR mRNA was present throughout all levels of the WT ferret and IBMX/forskolin-inducible ISC was only observed in WT animals. However, despite the lack of CFTR function in the knockout ferret, the luminal pH of the CF ferret gallbladder, stomach, and intestines was not significantly changed relative to WT. The WT stomach and gallbladder exhibited significantly enhanced IBMX/forskolin ISC responses and inhibition by GlyH-101 relative to CF samples. These findings demonstrate that multiple organs affected by disease in the CF ferret have bioelectric abnormalities consistent with the lack of cAMP-mediated chloride transport.

Serving Real-Time Point Observation Data in netCDF using Climate and Forecasting Discrete Sampling Geometry Conventions

NASA Astrophysics Data System (ADS)

Ward-Garrison, C.; May, R.; Davis, E.; Arms, S. C.

2016-12-01

NetCDF is a set of software libraries and self-describing, machine-independent data formats that support the creation, access, and sharing of array-oriented scientific data. The Climate and Forecasting (CF) metadata conventions for netCDF foster the ability to work with netCDF files in general and useful ways. These conventions include metadata attributes for physical units, standard names, and spatial coordinate systems. While these conventions have been successful in easing the use of working with netCDF-formatted output from climate and forecast models, their use for point-based observation data has been less so. Unidata has prototyped using the discrete sampling geometry (DSG) CF conventions to serve, using the THREDDS Data Server, the real-time point observation data flowing across the Internet Data Distribution (IDD). These data originate in text format reports for individual stations (e.g. METAR surface data or TEMP upper air data) and are converted and stored in netCDF files in real-time. This work discusses the experiences and challenges of using the current CF DSG conventions for storing such real-time data. We also test how parts of netCDF's extended data model can address these challenges, in order to inform decisions for a future version of CF (CF 2.0) that would take advantage of features of the netCDF enhanced data model.

Investigating the effect of tablet thickness and punch curvature on density distribution using finite elements method.

PubMed

Diarra, Harona; Mazel, Vincent; Busignies, Virginie; Tchoreloff, Pierre

2015-09-30

Finite elements method was used to study the influence of tablet thickness and punch curvature on the density distribution inside convex faced (CF) tablets. The modeling of the process was conducted on 2 pharmaceutical excipients (anhydrous calcium phosphate and microcrystalline cellulose) by using Drucker-Prager Cap model in Abaqus(®) software. The parameters of the model were obtained from experimental tests. Several punch shapes based on industrial standards were used. A flat-faced (FF) punch and 3 convex faced (CF) punches (8R11, 8R8 and 8R6) with a diameter of 8mm were chosen. Different tablet thicknesses were studied at a constant compression force. The simulation of the compaction of CF tablets with increasing thicknesses showed an important change on the density distribution inside the tablet. For smaller thicknesses, low density zones are located toward the center. The density is not uniform inside CF tablets and the center of the 2 faces appears with low density whereas the distribution inside FF tablets is almost independent of the tablet thickness. These results showed that FF and CF tablets, even obtained at the same compression force, do not have the same density at the center of the compact. As a consequence differences in tensile strength, as measured by diametral compression, are expected. This was confirmed by experimental tests. Copyright © 2015 Elsevier B.V. All rights reserved.

A hybrid personalized data recommendation approach for geoscience data sharing

NASA Astrophysics Data System (ADS)

WANG, M.; Wang, J.

2016-12-01

Recommender systems are effective tools helping Internet users overcome information overloading. The two most widely used recommendation algorithms are collaborating filtering (CF) and content-based filtering (CBF). A number of recommender systems based on those two algorithms were developed for multimedia, online sells, and other domains. Each of the two algorithms has its advantages and shortcomings. Hybrid approaches that combine these two algorithms are better choices in many cases. In geoscience data sharing domain, where the items (datasets) are more informative (in space and time) and domain-specific, no recommender system is specialized for data users. This paper reports a dynamic weighted hybrid recommendation algorithm that combines CF and CBF for geoscience data sharing portal. We first derive users' ratings on items with their historical visiting time by Jenks Natural Break. In the CBF part, we incorporate the space, time, and subject information of geoscience datasets to compute item similarity. Predicted ratings were computed with k-NN method separately using CBF and CF, and then combined with weights. With training dataset we attempted to find the best model describing ideal weights and users' co-rating numbers. A logarithmic function was confirmed to be the best model. The model was then used to tune the weights of CF and CBF on user-item basis with test dataset. Evaluation results show that the dynamic weighted approach outperforms either solo CF or CBF approach in terms of Precision and Recall.

Improving chronic care delivery and outcomes: the impact of the cystic fibrosis Care Center Network.

PubMed

Mogayzel, Peter J; Dunitz, Jordan; Marrow, Laura C; Hazle, Leslie A

2014-04-01

Cystic fibrosis (CF) is a multisystem, life-shortening genetic disease that requires complex care. To facilitate this expert, multidisciplinary care, the CF Foundation established a Care Center Network and accredited the first care centres in 1961. This model of care brings together physicians and specialists from other disciplines to provide care, facilitate basic and clinical research, and educate the next generation of providers. Although the Care Center Network has been invaluable in achieving substantial gains in survival and quality of life, additional opportunities for improvements in CF care exist. In 1999, analysis of data from the CF Foundation's Patient Registry detected variation in care practices and outcomes across centres, identifying opportunities for improvement. In 2002, the CF Foundation launched a comprehensive quality improvement (QI) initiative to enhance care by assembling national experts to develop a strategic plan to disseminate QI training and processes throughout the Care Center Network. The QI strategies included developing leadership (nationally and within each care centre), identifying best CF care practices, and incorporating people with CF and their families into improvement efforts. The goal was to improve the care for every person with CF in the USA. Multiple tactics were undertaken to implement the strategic plan and disseminate QI training and tools throughout the Care Center Network. In addition, strategies to foster collaboration between care centre staff and individuals with CF and their families became a cornerstone of QI efforts. Today it is clear that the application of QI principles within the CF Care Center Network has improved adherence to clinical guidelines and achievement of important health outcomes.

The hyaloid vasculature facilitates basement membrane breakdown during choroid fissure closure in the zebrafish eye.

PubMed

James, Andrea; Lee, Chanjae; Williams, Andre M; Angileri, Krista; Lathrop, Kira L; Gross, Jeffrey M

2016-11-15

A critical aspect of vertebrate eye development is closure of the choroid fissure (CF). Defects in CF closure result in colobomas, which are a significant cause of childhood blindness worldwide. Despite the growing number of mutated loci associated with colobomas, we have a limited understanding of the cell biological underpinnings of CF closure. Here, we utilize the zebrafish embryo to identify key phases of CF closure and regulators of the process. Utilizing Laminin-111 as a marker for the basement membrane (BM) lining the CF, we determine the spatial and temporal patterns of BM breakdown in the CF, a prerequisite for CF closure. Similarly, utilizing a combination of in vivo time-lapse imaging, β-catenin immunohistochemistry and F-actin staining, we determine that tissue fusion, which serves to close the fissure, follows BM breakdown closely. Periocular mesenchyme (POM)-derived endothelial cells, which migrate through the CF to give rise to the hyaloid vasculature, possess distinct actin foci that correlate with regions of BM breakdown. Disruption of talin1, which encodes a regulator of the actin cytoskeleton, results in colobomas and these correlate with structural defects in the hyaloid vasculature and defects in BM breakdown. cloche mutants, which entirely lack a hyaloid vasculature, also possess defects in BM breakdown in the CF. Taken together, these data support a model in which the hyaloid vasculature and/or the POM-derived endothelial cells that give rise to the hyaloid vasculature contribute to BM breakdown during CF closure. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Dust Cloud Models: Sensitivity of Calculated Transmittances to Variations in Input Parameters

DTIC Science & Technology

1981-06-01

Artillery School ATTN: DELEW-M-STO (Dr. Steven Kovel) ATTN: ATSF- CF -R (CPT James M. Watson) White Sands Missile Range, NM 88002 Fort Sill, OK 73503 Office...STEWS-PT-AL (Laurel B. Saunders) ATTN: ATSF- CF -R White Sands Missile Range, RM 88002 Fort Sill, OK 73503 Commander Commandant US Army RAD Coordinator...Army Field Artillery School ATTN: OELEW-M-STO (Dr. Steven Kovel) ATTN: ATSF- CF -R (CPT James M. Watson) White Sands Missile Range, NM 88002 Fort Sill, OK

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.

Bronchiectasis in infants and preschool children diagnosed with cystic fibrosis after newborn screening.

PubMed

Stick, Stephen M; Brennan, Siobhain; Murray, Conor; Douglas, Tonia; von Ungern-Sternberg, Britta S; Garratt, Luke W; Gangell, Catherine L; De Klerk, Nicholas; Linnane, Barry; Ranganathan, Sarath; Robinson, Phillip; Robertson, Colin; Sly, Peter D

2009-11-01

To determine the prevalence of bronchiectasis in young children with cystic fibrosis (CF) diagnosed after newborn screening (NBS) and the relationship of bronchiectasis to pulmonary inflammation and infection. Children were diagnosed with CF after NBS. Computed tomography and bronchoalveolar lavage were performed with anesthesia (n = 96). Scans were analyzed for the presence and extent of abnormalities. The prevalence of bronchiectasis was 22% and increased with age (P = .001). Factors associated with bronchiectasis included absolute neutrophil count (P = .03), neutrophil elastase concentration (P = .001), and Pseudomonas aeruginosa infection (P = .03). Pulmonary abnormalities are common in infants and young children with CF and relate to neutrophilic inflammation and infection with P. aeruginosa. Current models of care for infants with CF fail to prevent respiratory sequelae. Bronchiectasis is a clinically relevant endpoint that could be used for intervention trials that commence soon after CF is diagnosed after NBS.

SigB is a dominant regulator of virulence in Staphylococcus aureus small-colony variants.

PubMed

Mitchell, Gabriel; Fugère, Alexandre; Pépin Gaudreau, Karine; Brouillette, Eric; Frost, Eric H; Cantin, André M; Malouin, François

2013-01-01

Staphylococcus aureus small-colony variants (SCVs) are persistent pathogenic bacteria characterized by slow growth and, for many of these strains, an increased ability to form biofilms and to persist within host cells. The virulence-associated gene expression profile of SCVs clearly differs from that of prototypical strains and is often influenced by SigB rather than by the agr system. One objective of this work was to confirm the role of SigB in the control of the expression of virulence factors involved in biofilm formation and intracellular persistence of SCVs. This study shows that extracellular proteins are involved in the formation of biofilm by three SCV strains, which, additionally, have a low biofilm-dispersing activity. It was determined that SigB activity modulates biofilm formation by strain SCV CF07-S and is dominant over that of the agr system without being solely responsible for the repression of proteolytic activity. On the other hand, the expression of fnbA and the control of nuclease activity contributed to the SigB-dependent formation of biofilm of this SCV strain. SigB was also required for the replication of CF07-S within epithelial cells and may be involved in the colonization of lungs by SCVs in a mouse infection model. This study methodically investigated SigB activity and associated mechanisms in the various aspects of SCV pathogenesis. Results confirm that SigB activity importantly influences the production of virulence factors, biofilm formation and intracellular persistence for some clinical SCV strains.

Spatial variations in shear stress in a 3-D bifurcation model at low Reynolds numbers.

PubMed

Rouhanizadeh, Mahsa; Lin, Tiantian C; Arcas, Diego; Hwang, Juliana; Hsiai, Tzung K

2005-10-01

Real-time wall shear stress is difficult to monitor precisely because it varies in space and time. Microelectromechanical systems sensor provides high spatial resolution to resolve variations in shear stress in a 3-D bifurcation model for small-scaled hemodynamics. At low Reynolds numbers from 1.34 to 6.7 skin friction coefficients (C(f)) varied circumferentially by a factor of two or more within the bifurcation. At a Reynolds number of 6.7, the C(f) value at the lateral wall of the bifurcation along the 270 degree plane was 7.1, corresponding to a shear stress value of 0.0061 dyn/cm(2). Along the 180 degree plane, C(f) was 13 or 0.0079 dyn/cm(2), and at the medial wall along the 90 degree plane, C(f) was 10.3 or 0.0091 dyn/cm(2). The experimental skin friction coefficients correlated with values derived from the Navier-Stokes solutions.

Comparison of Carotid-Femoral and Brachial-Ankle Pulse-Wave Velocity in Association With Target Organ Damage in the Community-Dwelling Elderly Chinese: The Northern Shanghai Study.

PubMed

Lu, Yuyan; Zhu, Mengyun; Bai, Bin; Chi, Chen; Yu, Shikai; Teliewubai, Jiadela; Xu, Henry; Wang, Kai; Xiong, Jing; Zhou, Yiwu; Ji, Hongwei; Fan, Ximin; Yu, Xuejing; Li, Jue; Blacher, Jacques; Zhang, Yi; Xu, Yawei

2017-02-20

Carotid-femoral pulse-wave velocity (cf-PWV) and brachial-ankle PWV (ba-PWV) are the 2 most frequently applied PWV measurements. However, little is known about the comparison of hypertensive target organ damage (TOD) with cf-PWV and ba-PWV. A total of 1599 community-dwelling elderly subjects (age >65 years) in northern Shanghai were recruited from June 2014 to August 2015. Both cf-PWV and ba-PWV were measured using SphygmoCor and VP1000 systems, respectively. Within the framework of comprehensive cardiovascular examinations, risk factors were assessed, and asymptomatic TOD, including left ventricular mass index, peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity (E/Ea), carotid intima-media thickness, arterial plaque, creatinine clearance rate, and urinary albumin-creatinine ratio were all evaluated. Both PWVs were significantly associated with male sex, age, waist/hip circumference, fasting plasma glucose, and systolic blood pressure, and ba-PWV was also significantly related to body mass index. Both PWVs were significantly correlated with most TOD. When cf-PWV and ba-PWV were both or separately put into the stepwise linear regression model together with cardiovascular risk factors and treatment, only cf-PWV, but not ba-PWV, was significantly associated with carotid intima-media thickness and creatinine clearance rate ( P <0.05). When cf-PWV and ba-PWV were both or separately put into the same full-mode model after adjustment for confounders, only cf-PWV, but not ba-PWV, showed significant association with carotid intima-media thickness and creatinine clearance rate ( P <0.05). Similar results were observed in logistic regression analysis. Taken together, in the community-dwelling elderly Chinese, cf-PWV seems to be more closely associated with hypertensive TOD, especially vascular and renal TOD, as compared with ba-PWV. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02368938. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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.

A Comparison of Two Fat Grafting Methods on Operating Room Efficiency and Costs.

PubMed

Gabriel, Allen; Maxwell, G Patrick; Griffin, Leah; Champaneria, Manish C; Parekh, Mousam; Macarios, David

2017-02-01

Centrifugation (Cf) is a common method of fat processing but may be time consuming, especially when processing large volumes. To determine the effects on fat grafting time, volume efficiency, reoperations, and complication rates of Cf vs an autologous fat processing system (Rv) that incorporates fat harvesting and processing in a single unit. We performed a retrospective cohort study of consecutive patients who underwent autologous fat grafting during reconstructive breast surgery with Rv or Cf. Endpoints measured were volume of fat harvested (lipoaspirate) and volume injected after processing, time to complete processing, reoperations, and complications. A budget impact model was used to estimate cost of Rv vs Cf. Ninety-eight patients underwent fat grafting with Rv, and 96 patients received Cf. Mean volumes of lipoaspirate (506.0 vs 126.1 mL) and fat injected (177.3 vs 79.2 mL) were significantly higher (P < .0001) in the Rv vs Cf group, respectively. Mean time to complete fat grafting was significantly shorter in the Rv vs Cf group (34.6 vs 90.1 minutes, respectively; P < .0001). Proportions of patients with nodule and cyst formation and/or who received reoperations were significantly less in the Rv vs Cf group. Based on these outcomes and an assumed per minute operating room cost, an average per patient cost savings of $2,870.08 was estimated with Rv vs Cf. Compared to Cf, the Rv fat processing system allowed for a larger volume of fat to be processed for injection and decreased operative time in these patients, potentially translating to cost savings. LEVEL OF EVIDENCE 3. © 2016 The American Society for Aesthetic Plastic Surgery, Inc.

Behavioral alterations in cystic fibrosis mice are prevented by cannabinoid treatment in infancy.

PubMed

Bregman, Tatiana; Fride, Ester

2011-06-17

Substantial data have been accumulated regarding the molecular basis of cystic fibrosis (CF) pathogenesis, whereas the influence of biochemical impairments on brain processes has been the focus of much less attention. We have studied some behavioral parameters, such as motor activity and anxiety level, in a mice model of CF. We have assumed that functioning of the endocannabinoid system could be impaired in CF (endocannabinoids are fatty acid derivatives, and fatty acid deficiency is considered a major factor in CF etiology). We have suggested that chronic treatment with cannabinoid receptors agonist during infancy would balance cannabinoid levels and prevent CF-related behavioral alterations. Motor activity and anxiety level were studied in naïve adult CF mice (cftr-deficient mice) and compared with wild-type mice and to CF mice treated chronically with Δ9-tetrahydrocannabinol (Δ9-THC; endocannabinoid receptor agonist) during infancy (from days 7 to 28). Motor activity was tested in the tetrad, and level of anxiety in the plus maze, a month after cessation of treatment. Motor activity decrease and elevated anxiety level were found in adult naïve CF mice compared with wild-type mice. CF mice treated with THC in infancy showed normal motor activity and anxiety levels in adulthood. Motor function alteration and elevated anxiety levels in CF can result from lack of CFTR-channel in neurons and disturbed activity of various brain areas, as well as being secondary and mediated by fatty acids deficiency, altered levels of endocannabinoids and their receptors. It can be suggested that chronic treatment during infancy restores endocannabinoid function and thus prevents behavioral alterations.

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.

A story of success: continuous quality improvement in cystic fibrosis care in the USA.

PubMed

Quon, Bradley S; Goss, Christopher H

2011-12-01

Continuous quality improvement (CQI) in healthcare can be described as a reiterative approach to improving processes to reduce unexpected variation in health outcomes. CQI represents one model to achieve quality improvement (QI) and has long been recognized as a key to success in the manufacturing industry with companies like Toyota leading the way. Healthcare, and specifically pulmonary, critical care and sleep medicine represent ideal settings for the application of CQI. This opinion piece will describe QI and CQI initiatives in the US Cystic fibrosis (CF) population. QI in CF care in the United States has been ongoing since inception of the US CF Foundation (CFF) in 1955. This effort has included work to improve the quality of clinical care provided at CF centers and work to improve clinical outcomes in CF. More recently, QI methods have been applied to the conduct of clinical research. The CF community has become a leader in the area of QI and has pointed out the opportunities for others to follow in the area of lung diseases.

The association of visual memory with hippocampal volume.

PubMed

Zammit, Andrea R; Ezzati, Ali; Katz, Mindy J; Zimmerman, Molly E; Lipton, Michael L; Sliwinski, Martin J; Lipton, Richard B

2017-01-01

In this study we investigated the role of hippocampal volume (HV) in visual memory. Participants were a subsample of older adults (> = 70 years) from the Einstein Aging Study. Visual performance was measured using the Complex Figure (CF) copy and delayed recall tasks from the Repeatable Battery for the Assessment of Neuropsychological Status. Linear regressions were fitted to study associations between HV and visual tasks. Participants' (n = 113, mean age = 78.9 years) average scores on the CF copy and delayed recall were 17.4 and 11.6, respectively. CF delayed recall was associated with total (β = .031, p = 0.001) and left (β = 0.031, p = 0.001) and right HVs (β = 0.24, p = 0.012). CF delayed recall remained significantly associated with left HV even after we also included right HV (β = 0.27, p = 0.025) and the CF copy task (β = 0.30, p = 0.009) in the model. CF copy did not show any significant associations with HV. Our results suggest that left HV contributes in retrieval of visual memory in older adults.

Facile one-pot fabrication of nano-Fe3O4/carboxyl-functionalized baker's yeast composites and their application in methylene blue dye adsorption

NASA Astrophysics Data System (ADS)

Du, Zongjun; Zhang, Yue; Li, Zhengjie; Chen, Hui; Wang, Ying; Wang, Guangtu; Zou, Ping; Chen, Huaping; Zhang, Yunsong

2017-01-01

Nano-Fe3O4/carboxyl-functionalized baker's yeast composites (NF/CF-BYs) were prepared for the first time based on the ultrasonic cavitation assisted oxygen implosion method using single Fe2+ as iron source. The series of characterization analysis results showed that the obtained NF/CF-BYs had not only the superparamagnetic properties of nano-Fe3O4, but their surface also had plenty of functional groups (especially carboxyl groups) introduced by strong oxidization. The adsorption properties of NF/CF-BYs for methylene blue (MB) were also evaluated. The results displayed that the uptakes of NF/CF-BYs for MB were higher than that of pristine baker's yeast (P-BYs), and the adsorption process was followed by the pseudo-second-order kinetic model and Langmuir isotherm. The maximum adsorption capacity of NF/CF-BYs for MB was estimated to be 141.75 mg g-1 at pH 6. The regeneration efficiency of the obtained NF/CF-BYs was attained to be more than 90%.

Modeling, Fabrication and Characterization of Scalable Electroless Gold Plated Nanostructures for Enhanced Surface Plasmon Resonance

NASA Astrophysics Data System (ADS)

Jang, Gyoung Gug

The scientific and industrial demand for controllable thin gold (Au) film and Au nanostructures is increasing in many fields including opto-electronics, photovoltaics, MEMS devices, diagnostics, bio-molecular sensors, spectro-/microscopic surfaces and probes. In this study, a novel continuous flow electroless (CF-EL) Au plating method is developed to fabricate uniform Au thin films in ambient condition. The enhanced local mass transfer rate and continuous deposition resulting from CF-EL plating improved physical uniformity of deposited Au films and thermally transformed nanoparticles (NPs). Au films and NPs exhibited improved optical photoluminescence (PL) and surface plasmon resonance (SPR), respectively, relative to batch immersion EL (BI-EL) plating. Suggested mass transfer models of Au mole deposition are consistent with optical feature of CF-EL and BI-EL films. The prototype CF-EL plating system is upgraded an automated scalable CF-EL plating system with real-time transmission UV-vis (T-UV) spectroscopy which provides the advantage of CF-EL plating, such as more uniform surface morphology, and overcomes the disadvantages of conventional EL plating, such as no continuous process and low deposition rate, using continuous process and controllable deposition rate. Throughout this work, dynamic morphological and chemical transitions during redox-driven self-assembly of Ag and Au film on silica surfaces under kinetic and equilibrium conditions are distinguished by correlating real-time T-UV spectroscopy with X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) measurements. The characterization suggests that four previously unrecognized time-dependent physicochemical regimes occur during consecutive EL deposition of silver (Ag) and Au onto tin-sensitized silica surfaces: self-limiting Ag activation; transitory Ag NP formation; transitional Au-Ag alloy formation during galvanic replacement of Ag by Au; and uniform morphology formation under controlled hydraulic conditions. A method to achieve the time-resolved optical profile of EL Au plating was devised and provided a new transitional EL Au film growth model which validated mass transfer model prediction of the deposited thickness of ≤100 nm thin films. As a part of the project, validation of mass transfer model, a spectrophotometric method for quantitative analysis of metal ion is developed that improves the limit of detection comparable to conventional instrumental analysis. The present work suggests that modeling, fabrication and characterization of this novel CF-EL plating method is performed to achieve an ultimate purpose: developing a reliable, inexpensive wet chemical process for controlled metal thin film and nanostructure fabrication.

Forecasting US ivacaftor outcomes and cost in cystic fibrosis patients with the G551D mutation.

PubMed

Dilokthornsakul, Piyameth; Hansen, Ryan N; Campbell, Jonathan D

2016-06-01

Ivacaftor, a breakthrough treatment for cystic fibrosis (CF) patients with the G551D genetic mutation, lacks long-term clinical and cost projections. This study forecasted outcomes and cost by comparing ivacaftor plus usual care versus usual care alone.A lifetime Markov model was conducted from a US payer perspective. The model consisted of five health states: 1) forced expiratory volume in 1 s (FEV1) % pred ≥70%, 2) 40%≤ FEV1 % pred <70%, 3) FEV1 % pred <40%, 4) lung transplantation and 5) death. All inputs were extracted from published literature. Budget impact was also estimated. We estimated ivacaftor's improvement in outcomes compared with a non-CF referent population.Ivacaftor was associated with 18.25 (95% credible interval (CrI) 13.71-22.20) additional life-years and 15.03 (95% CrI 11.13-18.73) additional quality-adjusted life-years (QALYs). Ivacaftor was associated with improvements in survival and QALYs equivalent to 68% and 56%, respectively, for the survival and QALY gaps between CF usual care and their non-CF peers. The incremental lifetime cost was $3 374 584. The budget impact was $0.087 per member per month.Ivacaftor increased life-years and QALYs in CF patients with the G551D mutation, and moved morbidity and mortality closer to that of their non-CF peers. Ivacaftor costs much more than usual care, but comes at a relatively limited budget impact. Copyright ©ERS 2016.

Simulation of mechano-electrical transduction in the cochlea considering basilar membrane vibration and the ionic current of the inner hair cells

NASA Astrophysics Data System (ADS)

Lee, Sinyoung; Koike, Takuji

2018-05-01

The inner hair cells (IHCs) in the cochlea transduce mechanical vibration of the basilar membrane (BM), caused by sound pressure, to electrical signals that are transported along the acoustic nerve to the brain. The mechanical vibration of the BM and the ionic behaviors of the IHCs have been investigated. However, consideration of the ionic behavior of the IHCs related to mechanical vibration is necessary to investigate the mechano-electrical transduction of the cochlea. In this study, a finite-element model of the BM, which takes into account the non-linear activities of the outer hair cells (OHCs), and an ionic current model of IHC were combined. The amplitudes and phases of the vibration at several points on the BM were obtained from the finite-element model by applying sound pressure. These values were fed into the ionic current model, and changes in membrane potential and calcium ion concentration of the IHCs were calculated. The membrane potential of the IHC at the maximum amplitude point (CF point) was higher than that at the non-CF points. The calcium ion concentration at the CF point was also higher than that at the non-CF points. These results suggest that the cochlea achieves its good frequency discrimination ability through mechano-electrical transduction.

Accounting for pH heterogeneity and variability in modelling human health risks from cadmium in contaminated land.

PubMed

Gay, J Rebecca; Korre, Anna

2009-07-01

The authors have previously published a methodology which combines quantitative probabilistic human health risk assessment and spatial statistical methods (geostatistics) to produce an assessment, incorporating uncertainty, of risks to human health from exposure to contaminated land. The model assumes a constant soil to plant concentration factor (CF(veg)) when calculating intake of contaminants. This model is modified here to enhance its use in a situation where CF(veg) varies according to soil pH, as is the case for cadmium. The original methodology uses sequential indicator simulation (SIS) to map soil concentration estimates for one contaminant across a site. A real, age-stratified population is mapped across the contaminated area, and intake of soil contaminants by individuals is calculated probabilistically using an adaptation of the Contaminated Land Exposure Assessment (CLEA) model. The proposed improvement involves not only the geostatistical estimation of the contaminant concentration, but also that of soil pH, which in turn leads to a variable CF(veg) estimate which influences the human intake results. The results presented demonstrate that taking pH into account can influence the outcome of the risk assessment greatly. It is proposed that a similar adaptation could be used for other combinations of soil variables which influence CF(veg).

A novel antiplatelet antibody therapy that induces cAMP-dependent endocytosis of the GPVI/Fc receptor γ-chain complex

PubMed Central

Takayama, Hiroshi; Hosaka, Yoshitaka; Nakayama, Kazuyuki; Shirakawa, Kamon; Naitoh, Katsuki; Matsusue, Tomokazu; Shinozaki, Mikihiko; Honda, Motoyasu; Yatagai, Yukiko; Kawahara, Tetsushi; Hirose, Jiro; Yokoyama, Tooru; Kurihara, Michiru; Furusako, Shoji

2008-01-01

Platelet adhesion to vascular subendothelium, mediated in part by interactions between collagen and glycoprotein VI (GPVI) complexed with Fc receptor γ-chain, is crucial for thrombus formation. Antiplatelet therapy benefits patients with various thrombotic and ischemic diseases, but the safety and efficacy of existing treatments are limited. Recent data suggest GPVI as a promising target for a novel antiplatelet therapy, for example, GPVI-specific Abs that deplete GPVI from the surface of platelets. Here, we characterized GPVI-specific auto-Abs (YA-Abs) from the first reported patient with ongoing platelet GPVI deficiency caused by the YA-Abs. To obtain experimentally useful human GPVI–specific mAbs with characteristics similar to YA-Abs, we generated human GPVI–specific mouse mAbs and selected 2 representative mAbs, mF1201 and mF1232, whose binding to GPVI was inhibited by YA-Abs. In vitro, mF1201, but not mF1232, induced human platelet activation and GPVI shedding, and mF1232 inhibited collagen-induced human platelet aggregation. Administration of mF1201 and mF1232 to monkeys caused GPVI immunodepletion with and without both significant thrombocytopenia and GPVI shedding, respectively. When a human/mouse chimeric form of mF1232 (cF1232) was labeled with a fluorescent endocytosis probe and administered to monkeys, fluorescence increased in circulating platelets and surface GPVI was lost. Loss of platelet surface GPVI mediated by cF1232 was successfully reproduced in vitro in the presence of a cAMP-elevating agent. Thus, we have characterized cAMP-dependent endocytosis of GPVI mediated by a human GPVI–specific mAb as what we believe to be a novel antiplatelet therapy. PMID:18382762

Clipped Random Wave Morphologies and the Analysis of the SAXS of an Ionomer Formed by Copolymerization of Tetrafluoroethylene and CF[subscript 2]=CFO(CF[subscript 2])[subscript 4]SO[subscript 3]H

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

Aieta, Niccolo V.; Stanis, Ronald J.; Horan, James L.

Using SAXS data, the microstructure of the ionomer formed by copolymerization of tetrafluoroethylene and CF{sub 2}=CFO(CF{sub 2}){sub 4}SO{sub 3}H films has been approached by two methods: a numerical method (the unified fit approach) utilizing a simple model of spherical scattering objects to determine the radius of gyration of different scattering features of the ionomer films and by a graphical method, the clipped random wave approach (CRW), using the scattering data and a porosity parameter to generate a random wave which is clipped to produce a real-space image of the microstructure. We studied films with EW of 733, 825, 900, andmore » 1082 in both the as-cast and annealed 'dry' and boiled 'wet' states. The results of the two data analysis techniques are in good size agreement with each other. In addition, the CRW model show striking similarities to the structure proposed in a recent dissipative particle dynamic models. This has been the first time to our knowledge that the CRW technique has been applied to a PFSA type ionomer.« less

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

A randomized controlled trial of conventional fraction and late course accelerated hyperfraction three-dimensional conformal radiotherapy for esophageal cancer.

PubMed

Wang, Jian-Hua; Lu, Xu-Jing; Zhou, Jian; Wang, Feng

2012-01-01

We compared the curative and side-effects in esophageal carcinoma treated by conventional fraction (CF) and late course accelerated hyperfraction (LCAF) three-dimensional conformal radiotherapy. Ninety-eight patients were randomly assigned to two different radiotherapy model groups. Fifty patients were treated using CF three-dimensional conformal radiotherapy at a total dose of 60-68 Gy; 2 Gy/F; 5 fractions/week (median 64 Gy), 48 patients were treated with LCAF (First CF-treated at the dose 40 Gy. Later, LCAF-treated 1.5 Gy/F; 2 fractions/day; 21-27 Gy; a total dose of 61-67 Gy; median 64 Gy). The data showed that the 1-, 2- and 3-year-survival rates in LCAF group were 79.2, 56.3, and 43.8%, compared to 74, 54, and 36% in CF group (P = 0.476). The 1-, 2- and 3-year-local control rates in LCAF group were 81.3, 62.5, and 50%, compared to 78, 58, and 42% in CF group (P = 0.454). In CF group, the incidence of radiation-induced esophagitis was lower than that in LCAF group (72 vs. 93.8%; P = 0.008) and there was no significant difference between rates of radiation-induced pneumonitis in CF and LCAF groups (10 vs. 6.25%; P = 0.498). It was concluded that the 1-, 2- and 3-year-local control and survival rates of esophageal carcinoma patients treated with LCAF were slightly better than CF radiotherapy; however, the radiation side-effects in LCAF group were greater than those in CF group.

[Study on the nutrition of alpine meadow based on hyperspectral data].

PubMed

Wang, Xun; Liu, Shu-Jie; Jia, Hai-Feng; Chai, Sha-Tuo; Dang, An-Rong; Liu, Xue-Hua; Hao, Li-Zhuang; Cui, Zhan-Hong

2012-10-01

Remote sensing monitoring of alpine grassland nutritional status is a key factor of grassland reasonable utilization, also a difficulty for dynamic vegetation monitoring. The present paper studies the correlations between vegetation nutrition and hyperspectral data. The results showed that two band ratio models have a significant correlation with biomass, air-DM, P, CF, and CP. MAXR models have a significant correlation with most of nutrition index when selected wavebands equaled five. On the whole, the MAXR model precedes two band ratio models. Using MAXR models to estimate air-DM, P and CF can obtain higher accuracy.

Prediction of Compressional Wave Velocity Using Regression and Neural Network Modeling and Estimation of Stress Orientation in Bokaro Coalfield, India

NASA Astrophysics Data System (ADS)

Paul, Suman; Ali, Muhammad; Chatterjee, Rima

2018-01-01

Velocity of compressional wave ( V P) of coal and non-coal lithology is predicted from five wells from the Bokaro coalfield (CF), India. Shear sonic travel time logs are not recorded for all wells under the study area. Shear wave velocity ( Vs) is available only for two wells: one from east and other from west Bokaro CF. The major lithologies of this CF are dominated by coal, shaly coal of Barakar formation. This paper focuses on the (a) relationship between Vp and Vs, (b) prediction of Vp using regression and neural network modeling and (c) estimation of maximum horizontal stress from image log. Coal characterizes with low acoustic impedance (AI) as compared to the overlying and underlying strata. The cross-plot between AI and Vp/ Vs is able to identify coal, shaly coal, shale and sandstone from wells in Bokaro CF. The relationship between Vp and Vs is obtained with excellent goodness of fit ( R 2) ranging from 0.90 to 0.93. Linear multiple regression and multi-layered feed-forward neural network (MLFN) models are developed for prediction Vp from two wells using four input log parameters: gamma ray, resistivity, bulk density and neutron porosity. Regression model predicted Vp shows poor fit (from R 2 = 0.28) to good fit ( R 2 = 0.79) with the observed velocity. MLFN model predicted Vp indicates satisfactory to good R2 values varying from 0.62 to 0.92 with the observed velocity. Maximum horizontal stress orientation from a well at west Bokaro CF is studied from Formation Micro-Imager (FMI) log. Breakouts and drilling-induced fractures (DIFs) are identified from the FMI log. Breakout length of 4.5 m is oriented towards N60°W whereas the orientation of DIFs for a cumulative length of 26.5 m is varying from N15°E to N35°E. The mean maximum horizontal stress in this CF is towards N28°E.

Patterned Roughness for Cross-flow Transition Control at Mach 6

NASA Astrophysics Data System (ADS)

Arndt, Alexander; Matlis, Eric; Semper, Michael; Corke, Thomas

2017-11-01

Experiments are performed to investigate patterned discrete roughness for transition control on a sharp right-circular cone at an angle of attack at Mach 6.0. The approach to transition control is based on exciting less-amplified (subcritical) stationary cross-flow (CF) modes that suppress the growth of the more-amplified (critical) CF modes, and thereby delay transition. The experiments were performed in the Air Force Academy Ludwieg Tube which is a conventional (noisy) design. The cone model is equipped with a motorized 3-D traversing mechanism that mounts on the support sting. The traversing mechanism held a closely-spaced pair of fast-response total pressure Pitot probes. The model utilized a removable tip to exchange between different tip-roughness conditions. Mean flow distortion x-development indicated that the transition Reynolds number increased by 25% with the addition of the subcritical roughness. The energy in traveling disturbances was centered in the band of most amplified traveling CF modes predicted by linear theory. The spatial pattern in the amplitude of the traveling CF modes indicated a nonlinear (sum and difference) interaction between the stationary and traveling CF modes that might explain differences in Retrans between noisy and quiet environments. Air Force Grant FA9550-15-1-0278.

A European regulatory perspective on cystic fibrosis: current treatments, trends in drug development and translational challenges for CFTR modulators.

PubMed

Ponzano, Stefano; Nigrelli, Giulia; Fregonese, Laura; Eichler, Irmgard; Bertozzi, Fabio; Bandiera, Tiziano; Galietta, Luis J V; Papaluca, Marisa

2018-06-30

In this article we analyse the current authorised treatments and trends in early drug development for cystic fibrosis (CF) in the European Union for the time period 2000-2016. The analysis indicates a significant improvement in the innovation and development of new potential medicines for CF, shifting from products that act on the symptoms of the disease towards new therapies targeting the cause of CF. However, within these new innovative medicines, results for CF transmembrane conductance regulator (CFTR) modulators indicate that one major challenge for turning a CF concept product into an actual medicine for the benefit of patients resides in the fact that, although pre-clinical models have shown good predictability for certain mutations, a good correlation to clinical end-points or biomarkers ( e.g. forced expiratory volume in 1 s and sweat chloride) for all mutations has not yet been achieved. In this respect, the use of alternative end-points and innovative nonclinical models could be helpful for the understanding of those translational discrepancies. Collaborative endeavours to promote further research and development in these areas as well as early dialogue with the regulatory bodies available at the European competent authorities are recommended. Copyright ©ERS 2018.

Ab Initio Crystal Field for Lanthanides.

PubMed

Ungur, Liviu; Chibotaru, Liviu F

2017-03-13

An ab initio methodology for the first-principle derivation of crystal-field (CF) parameters for lanthanides is described. The methodology is applied to the analysis of CF parameters in [Tb(Pc) 2 ] - (Pc=phthalocyanine) and Dy 4 K 2 ([Dy 4 K 2 O(OtBu) 12 ]) complexes, and compared with often used approximate and model descriptions. It is found that the application of geometry symmetrization, and the use of electrostatic point-charge and phenomenological CF models, lead to unacceptably large deviations from predictions based on ab initio calculations for experimental geometry. It is shown how the predictions of standard CASSCF (Complete Active Space Self-Consistent Field) calculations (with 4f orbitals in the active space) can be systematically improved by including effects of dynamical electronic correlation (CASPT2 step) and by admixing electronic configurations of the 5d shell. This is exemplified for the well-studied Er-trensal complex (H 3 trensal=2,2',2"-tris(salicylideneimido)trimethylamine). The electrostatic contributions to CF parameters in this complex, calculated with true charge distributions in the ligands, yield less than half of the total CF splitting, thus pointing to the dominant role of covalent effects. This analysis allows the conclusion that ab initio crystal field is an essential tool for the decent description of lanthanides. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Heart Rate Dependency of Large Artery Stiffness.

PubMed

Tan, Isabella; Spronck, Bart; Kiat, Hosen; Barin, Edward; Reesink, Koen D; Delhaas, Tammo; Avolio, Alberto P; Butlin, Mark

2016-07-01

Carotid-femoral pulse wave velocity (cfPWV) quantifies large artery stiffness, it is used in hemodynamic research and is considered a useful cardiovascular clinical marker. cfPWV is blood pressure (BP) dependent. Intrinsic heart rate (HR) dependency of cfPWV is unknown because increasing HR is commonly accompanied by increasing BP. This study aims to quantify cfPWV dependency on acute, sympathovagal-independent changes in HR, independent of BP. Individuals (n=52, age 40-93 years, 11 female) with in situ cardiac pacemakers or cardioverter defibrillators were paced at 60, 70, 80, 90, and 100 bpm. BP and cfPWV were measured at each HR. Both cfPWV (mean [95% CI], 0.31 [0.26-0.37] m/s per 10 bpm; P<0.001) and central aortic diastolic pressure (3.78 [3.40-4.17] mm Hg/10 bpm; P<0.001) increased with HR. The HR effect on cfPWV was isolated by correcting the BP effects by 3 different methods: (1) statistically, by a linear mixed model; (2) mathematically, using an exponential relationship between BP and cross-sectional lumen area; and (3) using measured BP dependency of cfPWV derived from changes in BP induced by orthostatic changes (seated and supine) in a subset of subjects (n=17). The BP-independent effects of HR on cfPWV were quantified as 0.20 [0.11-0.28] m/s per 10 bpm (P<0.001, method 1), 0.16 [0.11-0.22] m/s per 10 bpm (P<0.001, method 2), and 0.16 [0.11-0.21] m/s per 10 bpm (P<0.001, method 3). With a mean HR dependency in the range of 0.16 to 0.20 m/s per 10 bpm, cfPWV may be considered to have minimal physiologically relevant changes for small changes in HR, but larger differences in HR must be considered as contributing to significant differences in cfPWV. © 2016 American Heart Association, Inc.

Bioelectric Characterization of Epithelia from Neonatal CFTR Knockout Ferrets

PubMed Central

Fisher, John T.; Tyler, Scott R.; Zhang, Yulong; Lee, Ben J.; Liu, Xiaoming; Sun, Xingshen; Sui, Hongshu; Liang, Bo; Luo, Meihui; Xie, Weiliang; Yi, Yaling; Zhou, Weihong; Song, Yi; Keiser, Nicholas; Wang, Kai; de Jonge, Hugo R.

2013-01-01

Cystic fibrosis (CF) is a life-shortening, recessive, multiorgan genetic disorder caused by the loss of CF transmembrane conductance regulator (CFTR) chloride channel function found in many types of epithelia. Animal models that recapitulate the human disease phenotype are critical to understanding pathophysiology in CF and developing therapies. CFTR knockout ferrets manifest many of the phenotypes observed in the human disease, including lung infections, pancreatic disease and diabetes, liver disease, malnutrition, and meconium ileus. In the present study, we have characterized abnormalities in the bioelectric properties of the trachea, stomach, intestine, and gallbladder of newborn CF ferrets. Short-circuit current (ISC) analysis of CF and wild-type (WT) tracheas revealed the following similarities and differences: (1) amiloride-sensitive sodium currents were similar between genotypes; (2) responses to 4,4′-diisothiocyano-2,2′-stilbene disulphonic acid were 3.3-fold greater in CF animals, suggesting elevated baseline chloride transport through non-CFTR channels in a subset of CF animals; and (3) a lack of 3-isobutyl-1-methylxanthine (IBMX)/forskolin–stimulated and N-(2-Naphthalenyl)-((3,5-dibromo-2,4-dihydroxyphenyl)methylene)glycine hydrazide (GlyH-101)–inhibited currents in CF animals due to the lack of CFTR. CFTR mRNA was present throughout all levels of the WT ferret and IBMX/forskolin–inducible ISC was only observed in WT animals. However, despite the lack of CFTR function in the knockout ferret, the luminal pH of the CF ferret gallbladder, stomach, and intestines was not significantly changed relative to WT. The WT stomach and gallbladder exhibited significantly enhanced IBMX/forskolin ISC responses and inhibition by GlyH-101 relative to CF samples. These findings demonstrate that multiple organs affected by disease in the CF ferret have bioelectric abnormalities consistent with the lack of cAMP-mediated chloride transport. PMID:23782101

DIRECT AND INDIRECT FLUORESCENT-ANTIBODY TECHNIQUES FOR THE PSITTACOSIS-LYMPHOGRANULOMA VENEREUM-TRACHOMA GROUP OF AGENTS1

PubMed Central

Ross, Martin R.; Borman, Earle K.

1963-01-01

Ross, Martin R. (Connecticut State Department of Health, Hartford) and Earle K. Borman. Direct and indirect fluorescent-antibody techniques for the psittacosis-lymphogranuloma venereum-trachoma group of agents. J. Bacteriol. 85:851–858. 1963.—Direct and indirect fluorescent-antibody (FA) techniques were developed for the detection of group antigen in infected tissue cultures and the titration of group antibody in human antiserum. The growth of the agent of meningopneumonitis (MP) in mouse embryo lung cell monolayers was followed by infectivity and complement-fixing (CF) antigen titrations, and cytological examination of FA stained cultures. Although infectivity and CF antigen reached a peak at 2 days and remained constant for an additional 3 days, only cells tested 2 to 3 days after infection were suitable for FA staining with labeled anti-MP serum because of excessive artifacts in the older cultures. Fluorescein isothiocyanate-labeled rooster and guinea pig anti-MP serums and human antipsittacosis serums were titrated in direct FA and hemagglutination-inhibition (HI) tests. The rooster conjugate showed brighter staining and higher antibody titers than the guinea pig or human conjugates and was more effective in detecting minimal amounts of virus antigen. FA staining reactions with 1 and 2 units of labeled rooster serum were inhibited by unlabeled rooster serum but clear-cut inhibition with human antipsittacosis serum could not be demonstrated. The indirect FA technique was successfully used for the titration of group antibody in human serum. A comparison of the indirect FA, HI, and CF tests showed the indirect FA technique to be intermediate in sensitivity between the HI and CF tests. None of the three tests showed significant cross reactions with human serums reactive for influenza A and B; parainfluenza 1, 2, and 3; respiratory syncytial virus; Q fever; or the primary atypical pneumonia agent. PMID:14044954

Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation.

PubMed

Sampaziotis, Fotios; de Brito, Miguel Cardoso; Madrigal, Pedro; Bertero, Alessandro; Saeb-Parsy, Kourosh; Soares, Filipa A C; Schrumpf, Elisabeth; Melum, Espen; Karlsen, Tom H; Bradley, J Andrew; Gelson, William Th; Davies, Susan; Baker, Alastair; Kaser, Arthur; Alexander, Graeme J; Hannan, Nicholas R F; Vallier, Ludovic

2015-08-01

The study of biliary disease has been constrained by a lack of primary human cholangiocytes. Here we present an efficient, serum-free protocol for directed differentiation of human induced pluripotent stem cells into cholangiocyte-like cells (CLCs). CLCs show functional characteristics of cholangiocytes, including bile acids transfer, alkaline phosphatase activity, γ-glutamyl-transpeptidase activity and physiological responses to secretin, somatostatin and vascular endothelial growth factor. We use CLCs to model in vitro key features of Alagille syndrome, polycystic liver disease and cystic fibrosis (CF)-associated cholangiopathy. Furthermore, we use CLCs generated from healthy individuals and patients with polycystic liver disease to reproduce the effects of the drugs verapamil and octreotide, and we show that the experimental CF drug VX809 rescues the disease phenotype of CF cholangiopathy in vitro. Our differentiation protocol will facilitate the study of biological mechanisms controlling biliary development, as well as disease modeling and drug screening.

Compassion fatigue, burnout and compassion satisfaction in neonatologists in the US.

PubMed

Weintraub, A S; Geithner, E M; Stroustrup, A; Waldman, E D

2016-11-01

Compassion fatigue (CF) is distress experienced by caregivers from ongoing contact with patients who are suffering. Burnout (BO) is occupational stress directly related to dissonance between job demands and available resources. Compassion satisfaction (CS) is professional fulfillment experienced through helping others. CF in physicians is not well studied. Neonatologists may be at particular risk for CF by virtue of recurrent exposure to distress in patients and their families. The objectives of this study were to determine the prevalence of CF, BO and CS, and to identify potential predictors for these phenomena in neonatologists. A modified Compassion Fatigue and Satisfaction Self-Test and a questionnaire of professional details and personal characteristics were distributed electronically to neonatologists nationally. Multivariable logistic and linear regression models for CF, BO and CS as a function of potential predictors were constructed. The survey response rate was 47%. The prevalence of CF, BO and CS was 15.7, 20.8 and 21.9%, respectively. Female gender, emotional depletion, distress from 'a clinical situation', 'co-workers', 'personal health issues' and 'not talking about distressing issues' were each significant determinants of CF. Emotional depletion, distress from the 'physical work environment' and 'co-workers', and 'not talking about distressing issues' were significant determinants of BO. Self-identification as Hispanic; 'not currently feeling distressed'; talking about distressing issues; and utilization of pediatric palliative care services were significant determinants of higher CS. CF and BO may impact emotional well-being and professional performance of neonatologists. Enhancement of CS is a potential target for intervention.

Macrophage Migration Inhibitory Factor Enzymatic Activity, Lung Inflammation, and Cystic Fibrosis

PubMed Central

Adamali, Huzaifa; Armstrong, Michelle E.; McLaughlin, Anne Marie; Cooke, Gordon; McKone, Edward; Costello, Christine M.; Gallagher, Charles G.; Leng, Lin; Baugh, John A.; Fingerle-Rowson, Günter; Bucala, Richard J.; McLoughlin, Paul

2012-01-01

Rationale: Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator with unique tautomerase enzymatic activity; the precise function has not been clearly defined. We previously demonstrated that individual patients with cystic fibrosis (CF) who are genetically predisposed to be high MIF producers develop accelerated end-organ injury. Objectives: To characterize the effects of the MIF-CATT polymorphism in patients with CF ex vivo. To investigate the role of MIF’s tautomerase activity in a murine model of Pseudomonas aeruginosa infection. Methods: MIF and tumor necrosis factor (TNF)-α protein levels were assessed in plasma or peripheral blood mononuclear cell (PBMC) supernatants by ELISA. A murine pulmonary model of chronic Pseudomonas infection was used in MIF wild-type mice (mif+/+) and in tautomerase-null, MIF gene knockin mice (mif P1G/P1G). Measurements and Main Results: MIF protein was measured in plasma and PBMCs from 5- and 6-CATT patients with CF; LPS-induced TNF-α production from PBMCs was also assessed. The effect of a specific inhibitor of MIF-tautomerase activity, ISO-1, was investigated in PBMCs. In the murine infection model, total weight loss, differential cell counts, bacterial load, and intraacinar airspace/tissue volume were measured. MIF and TNF-α levels were increased in 6-CATT compared with 5-CATT patients with CF. LPS-induced TNF-α production from PBMCs was attenuated in the presence of ISO-1. In a murine model of Pseudomonas infection, significantly less pulmonary inflammation and bacterial load was observed in mifP1G/P1G compared with mif+/+ mice. Conclusions: MIF-tautomerase activity may provide a novel therapeutic target in patients with chronic inflammatory diseases such as CF, particularly those patients who are genetically predisposed to produce increased levels of this cytokine. PMID:22592805

A model of irreversible jam formation in dense traffic

NASA Astrophysics Data System (ADS)

Brankov, J. G.; Bunzarova, N. Zh.; Pesheva, N. C.; Priezzhev, V. B.

2018-03-01

We study an one-dimensional stochastic model of vehicular traffic on open segments of a single-lane road of finite size L. The vehicles obey a stochastic discrete-time dynamics which is a limiting case of the generalized Totally Asymmetric Simple Exclusion Process. This dynamics has been previously used by Bunzarova and Pesheva (2017) for an one-dimensional model of irreversible aggregation. The model was shown to have three stationary phases: a many-particle one, MP, a phase with completely filled configuration, CF, and a boundary perturbed MP+CF phase, depending on the values of the particle injection (α), ejection (β) and hopping (p) probabilities. Here we extend the results for the stationary properties of the MP+CF phase, by deriving exact expressions for the local density at the first site of the chain and the probability P(1) of a completely jammed configuration. The unusual phase transition, characterized by jumps in both the bulk density and the current (in the thermodynamic limit), as α crosses the boundary α = p from the MP to the CF phase, is explained by the finite-size behavior of P(1). By using a random walk theory, we find that, when α approaches from below the boundary α = p, three different regimes appear, as the size L → ∞: (i) the lifetime of the gap between the rightmost clusters is of the order O(L) in the MP phase; (ii) small jams, separated by gaps with lifetime O(1) , exist in the MP+CF phase close to the left chain boundary; and (iii) when β = p, the jams are divided by gaps with lifetime of the order O(L 1 / 2) . These results are supported by extensive Monte Carlo calculations.

Organic rankine cycle fluid

DOEpatents

Brasz, Joost J.; Jonsson, Ulf J.

2006-09-05

A method of operating an organic rankine cycle system wherein a liquid refrigerant is circulated to an evaporator where heat is introduced to the refrigerant to convert it to vapor. The vapor is then passed through a turbine, with the resulting cooled vapor then passing through a condenser for condensing the vapor to a liquid. The refrigerant is one of CF.sub.3CF.sub.2C(O)CF(CF.sub.3).sub.2, (CF.sub.3).sub.2 CFC(O)CF(CF.sub.3).sub.2, CF.sub.3(CF.sub.2).sub.2C(O)CF(CF.sub.3).sub.2, CF.sub.3(CF.sub.2).sub.3C(O)CF(CG.sub.3).sub.2, CF.sub.3(CF.sub.2).sub.5C(O)CF.sub.3, CF.sub.3CF.sub.2C(O)CF.sub.2CF.sub.2CF.sub.3, CF.sub.3C(O)CF(CF.sub.3).sub.2.

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...

Disparities in Mortality of Hispanic Cystic Fibrosis Patients in the United States: A National and Regional Cohort Study.

PubMed

Rho, Jason; Ahn, Chul; Gao, Ang; Sawicki, Gregory S; Keller, Ashley; Jain, Raksha

2018-05-09

Cystic Fibrosis (CF) patients of Hispanic origin are the largest growing minority, representing 8.5% of CF patients in the United States. No national survival analysis of this group has ever been undertaken. We aimed to determine whether Hispanic ethnicity within the CF population is associated with worse outcomes and whether any geographic differences exist. Using U.S. CF Foundation Patient Registry data from 2010-2014, we performed a retrospective cohort analysis comparing survival rates between Hispanics and non-Hispanics using Kaplan-Meier and Cox regression analysis. A subject's residence was categorized into geographic regions based on U.S. Census Bureau data: Northeast, Midwest, West and South. 29,637 patients were included in the study; 2,493 identified themselves as Hispanic. Hispanics had a lower survival probability overall, with a mean age of death of 22.4 ± 9.9 years compared to non-Hispanics of 28.1 ± 10.0 years (p < 0.0001). Multivariate cox proportional hazards modeling revealed that Hispanic CF patients had a 1.27 times higher rate of death compared to non-Hispanics (95% CI: 1.05 - 1.53) after adjusting for covariates including age, sex, genetic mutations, bacterial cultures, lung function, body mass index, use of CF respiratory therapies, low socioeconomic status, pancreatic enzyme use, and CF-related diabetes. When analyzed by region, Hispanics in the Midwest, Northeast, and West had shorter median survivals compared to Non-Hispanics, which was not demonstrated in the South. CF patients of Hispanic origin have a higher mortality rate than non-Hispanic CF patients. This pattern was seen in the Midwest, Northeast, and West but not in the South.

THE INVESTIGATION OF EFFECT OF FLURBIPROFEN AXETIL ON THE TISSUE GROWTH AND THE CONTENT OF PGE2 IN CERVICAL CANCER.

PubMed

Lu, Jing; Wang, Shenggang; Chen, Guiying; Sun, Xiaofeng; Li, Kezhong

2016-11-01

The aim of this study was to investigate whether flurbiprofen axetil can inhibit the tissue growth and the content of PGE2 in cervical cancer or not. Fifty female BALB/c nude mice were randomly divided into control group (C), tumor + saline group (T), tumor + flurbiprofen axetil 10 mg/kg (Cfl0) group, tumor + flurbiprofen axetil 25 mg/kg (Cf25) group, tumor + flurbiprofen axetil tumor 50 mg/kg (Cf50), so that each group had 10 animals. Then, the animal model of human cervical carcinoma was established, and the relative tumor volume (RTV), relative tumor proliferation rate (T/C) and tumor inhibition rate were measured. The content of PGE2 in tumor tissue was determined by using enzyme-linked immunosorbent assay. There was no tumor formation in group C, and the time of tumor growth in other groups was non-statistically different. The RVT in Cf50 group was lower than in other groups. It was evident from the curve of tumor growth that the tumor weight in T group was evidently higher than that of administration groups (p < 0.01). The tumor inhibition rates of Cf10, Cf25 and Cf50 groups were 16.8, 19.6 and 36%, respectively, and the relative tumor proliferation rate were 85, 91 and 72%, respectively. The PGE, level of Cf50 was statistically (p < 0.01) lower than that of Cfl0 and Cf25 groups. Flurbiprofen axetil can inhibit the growth of cervical cancer transplanted tumor in nude mice and this inhibitory effect was maximal in Cf50 group. Flurbiprofen axetil can inhibit the production of PGE2 in tumor tissue of cervical carcinoma in nude mice.

Impact of Gene Patents and Licensing Practices on Access to Genetic Testing for Cystic Fibrosis

PubMed Central

Chandrasekharan, Subhashini; Heaney, Christopher; James, Tamara; Conover, Chris; Cook-Deegan, Robert

2010-01-01

Cystic fibrosis (CF) is one of the most commonly tested autosomal recessive disorders in the US. Clinical CF is associated with mutations in the CFTR gene, of which the most common mutation among Caucasians, ΔF508, was identified in 1989. The University of Michigan, Johns Hopkins University, and the Hospital for Sick Children, where much of the initial research occurred, hold key patents for CF genetic sequences, mutations and methods for detecting them. Several patents including the one that covers detection of the ΔF508 mutation are jointly held by the University of Michigan and the Hospital for Sick Children in Toronto, with Michigan administering patent licensing in the US. The University of Michigan broadly licenses the ΔF508 patent for genetic testing with over 60 providers of genetic testing to date. Genetic testing is now used in newborn screening, diagnosis, and reproductive decisions. Interviews with key researchers and intellectual property managers, a survey of laboratories’ prices for CF genetic testing, a review of literature on CF tests’ cost effectiveness, and a review of the developing market for CF testing provide no evidence that patents have significantly hindered access to genetic tests for CF or prevented financially cost-effective screening. Current licensing practices for cystic fibrosis (CF) genetic testing appear to facilitate both academic research and commercial testing. More than one thousand different CFTR mutations have been identified, and research continues to determine their clinical significance. Patents have been nonexclusively licensed for diagnostic use, and have been variably licensed for gene transfer and other therapeutic applications. The Cystic Fibrosis Foundation has been engaged in licensing decisions, making CF a model of collaborative and cooperative patenting and licensing practice. PMID:20393308

Mutations of Cystic Fibrosis Transmembrane Conductance Regulator Gene Cause a Monocyte-Selective Adhesion Deficiency.

PubMed

Sorio, Claudio; Montresor, Alessio; Bolomini-Vittori, Matteo; Caldrer, Sara; Rossi, Barbara; Dusi, Silvia; Angiari, Stefano; Johansson, Jan E; Vezzalini, Marzia; Leal, Teresinha; Calcaterra, Elisa; Assael, Baroukh M; Melotti, Paola; Laudanna, Carlo

2016-05-15

Cystic fibrosis (CF) is a common genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Persistent lung inflammation, characterized by increasing polymorphonuclear leukocyte recruitment, is a major cause of the decline in respiratory function in patients with CF and is a leading cause of morbidity and mortality. CFTR is expressed in various cell types, including leukocytes, but its involvement in the regulation of leukocyte recruitment is unknown. We evaluated whether CF leukocytes might present with alterations in cell adhesion and migration, a key process governing innate and acquired immune responses. We used ex vivo adhesion and chemotaxis assays, flow cytometry, immunofluorescence, and GTPase activity assays in this study. We found that chemoattractant-induced activation of β1 and β2 integrins and of chemotaxis is defective in mononuclear cells isolated from patients with CF. In contrast, polymorphonuclear leukocyte adhesion and chemotaxis were normal. The functionality of β1 and β2 integrins was restored by treatment of CF monocytes with the CFTR-correcting drugs VRT325 and VX809. Moreover, treatment of healthy monocytes with the CFTR inhibitor CFTR(inh)-172 blocked integrin activation by chemoattractants. In a murine model of lung inflammation, we found that integrin-independent migration of CF monocytes into the lung parenchyma was normal, whereas, in contrast, integrin-dependent transmigration into the alveolar space was impaired. Finally, signal transduction analysis showed that, in CF monocytes, chemoattractant-triggered activation of RhoA and CDC42 Rho small GTPases (controlling integrin activation and chemotaxis, respectively) was strongly deficient. Altogether, these data highlight the critical regulatory role of CFTR in integrin activation by chemoattractants in monocytes and identify CF as a new, cell type-selective leukocyte adhesion deficiency disease, providing new insights into CF pathogenesis.

Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs

PubMed Central

Stoltz, David A.; Rokhlina, Tatiana; Ernst, Sarah E.; Pezzulo, Alejandro A.; Ostedgaard, Lynda S.; Karp, Philip H.; Samuel, Melissa S.; Reznikov, Leah R.; Rector, Michael V.; Gansemer, Nicholas D.; Bouzek, Drake C.; Alaiwa, Mahmoud H. Abou; Hoegger, Mark J.; Ludwig, Paula S.; Taft, Peter J.; Wallen, Tanner J.; Wohlford-Lenane, Christine; McMenimen, James D.; Chen, Jeng-Haur; Bogan, Katrina L.; Adam, Ryan J.; Hornick, Emma E.; Nelson, George A.; Hoffman, Eric A.; Chang, Eugene H.; Zabner, Joseph; McCray, Paul B.; Prather, Randall S.; Meyerholz, David K.; Welsh, Michael J.

2013-01-01

Cystic fibrosis (CF) pigs develop disease with features remarkably similar to those in people with CF, including exocrine pancreatic destruction, focal biliary cirrhosis, micro-gallbladder, vas deferens loss, airway disease, and meconium ileus. Whereas meconium ileus occurs in 15% of babies with CF, the penetrance is 100% in newborn CF pigs. We hypothesized that transgenic expression of porcine CF transmembrane conductance regulator (pCFTR) cDNA under control of the intestinal fatty acid–binding protein (iFABP) promoter would alleviate the meconium ileus. We produced 5 CFTR–/–;TgFABP>pCFTR lines. In 3 lines, intestinal expression of CFTR at least partially restored CFTR-mediated anion transport and improved the intestinal phenotype. In contrast, these pigs still had pancreatic destruction, liver disease, and reduced weight gain, and within weeks of birth, they developed sinus and lung disease, the severity of which varied over time. These data indicate that expressing CFTR in intestine without pancreatic or hepatic correction is sufficient to rescue meconium ileus. Comparing CFTR expression in different lines revealed that approximately 20% of wild-type CFTR mRNA largely prevented meconium ileus. This model may be of value for understanding CF pathophysiology and testing new preventions and therapies. PMID:23676501

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.

A robust and accurate center-frequency estimation (RACE) algorithm for improving motion estimation performance of SinMod on tagged cardiac MR images without known tagging parameters.

PubMed

Liu, Hong; Wang, Jie; Xu, Xiangyang; Song, Enmin; Wang, Qian; Jin, Renchao; Hung, Chih-Cheng; Fei, Baowei

2014-11-01

A robust and accurate center-frequency (CF) estimation (RACE) algorithm for improving the performance of the local sine-wave modeling (SinMod) method, which is a good motion estimation method for tagged cardiac magnetic resonance (MR) images, is proposed in this study. The RACE algorithm can automatically, effectively and efficiently produce a very appropriate CF estimate for the SinMod method, under the circumstance that the specified tagging parameters are unknown, on account of the following two key techniques: (1) the well-known mean-shift algorithm, which can provide accurate and rapid CF estimation; and (2) an original two-direction-combination strategy, which can further enhance the accuracy and robustness of CF estimation. Some other available CF estimation algorithms are brought out for comparison. Several validation approaches that can work on the real data without ground truths are specially designed. Experimental results on human body in vivo cardiac data demonstrate the significance of accurate CF estimation for SinMod, and validate the effectiveness of RACE in facilitating the motion estimation performance of SinMod. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Theoretical research on the spin-Hamiltonian parameters of the rhombic W5+ centers in CaWO4:Y3+ crystal

NASA Astrophysics Data System (ADS)

Mei, Yang; Wei, Cheng-Fu; Zheng, Wen-Chen

2016-02-01

Detailed theoretical calculations for the spin-Hamiltonian parameters (g factors gi and hyperfine structure constants Ai, where i=x, y, z) of the rhombic W5+ center in CaWO4:Y3+ crystal are performed by using the high-order perturbation formulas for d1 ions in rhombic tetrahedral clusters with the ground state |dz2>. These formulas consist of the contributions from two mechanisms, the crystal-field (CF) mechanism connected with CF excited states in the vastly-used CF theory and the frequently-neglected charge-transfer (CT) mechanism related to CT excited states. The calculated results agree well with the experimental values. The calculations indicate that for W5+ ion (or other high valence state dn ions) in crystals, the model calculations of spin-Hamiltonian parameters should take both the CF and CT mechanisms into account. The signs of hyperfine structure constants Ai are suggested and the forming (or defect model) of rhombic W5+ center in CaWO4:Y3+ crystal is confirmed from the calculations.

Ground state of Ho atoms on Pt(111) metal surfaces: Implications for magnetism

NASA Astrophysics Data System (ADS)

Karbowiak, M.; Rudowicz, C.

2016-05-01

We investigated the ground state of Ho atoms adsorbed on the Pt(111) surface, for which conflicting results exist. The density functional theory (DFT) calculations yielded the Ho ground state as | Jz=±8 > . Interpretation of x-ray absorption spectroscopy and x-ray magnetic circular dichroism spectra and the magnetization curves indicated the ground state as | Jz=±6 > . Superposition model is employed to predict the crystal-field (CF) parameters based on the structural data for the system Ho/Pt(111) obtained from the DFT modeling. Simultaneous diagonalization of the free-ion (HFI) and the trigonal CF Hamiltonian (HCF) within the whole configuration 4 f10 of H o3 + ion was performed. The role of the trigonal CF terms, neglected in the pure uniaxial CF model used previously for interpretation of experimental spectra, is found significant, whereas the sixth-rank CF terms may be neglected in agreement with the DFT predictions. The results provide substantial support for the experimental designation of the | Jz=±6 > ground state, albeit with subtle difference due to admixture of other | Jz> states, but run against the DFT-based designation of the | Jz=±8 > ground state. A subtle splitting of the ground energy level with the state (predominantly), | Jz=±6 > is predicted. This paper provides better insight into the single-ion magnetic behavior of the Ho/Pt(111) system by helping to resolve the controversy concerning the Ho ground state. Experimental techniques with greater resolution powers are suggested for direct confirmation of this splitting and C3 v symmetry experienced by the Ho atom.

Developing a model for cystic fibrosis sociomicrobiology based on antibiotic and environmental stress.

PubMed

Lopes, Susana Patrícia; Azevedo, Nuno Filipe; Pereira, Maria Olívia

2017-12-01

Cystic fibrosis (CF) infections are invariably biofilm-mediated and polymicrobial, being safe to assume that a myriad of factors affects the sociomicrobiology within the CF infection site and modulate the CF community dynamics, by shaping their social activities, overall functions, virulence, ultimately affecting disease outcome. This work aimed to assess changes in the dynamics (particularly on the microbial composition) of dual-/three-species biofilms involving CF-classical (Pseudomonas aeruginosa) and unusual species (Inquilinus limosus and Dolosigranulum pigrum), according to variable oxygen conditions and antibiotic exposure. Low fluctuations in biofilm compositions were observed across distinct oxygen environments, with dual-species biofilms exhibiting similar relative proportions and P. aeruginosa and/or D. pigrum populations dominating three-species consortia. Once exposed to antibiotics, biofilms displayed high resistance profiles, and microbial compositions, distributions, and microbial interactions significantly challenged. The antibiotic/oxygen environment supported such fluctuations, which enhanced for three-species communities. In conclusion, antibiotic therapy hugely disturbed CF communities' dynamics, inducing significant compositional changes on multispecies consortia. Clearly, multiple perturbations may disturb this dynamic, giving rise to various microbiological scenarios in vivo, and affecting disease phenotype. Therefore, an appreciation of the ecological/evolutionary nature within CF communities will be useful for the optimal use of current therapies and for newer breakthroughs on CF antibiotherapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

Genomic sequencing in cystic fibrosis newborn screening: what works best, two-tier predefined CFTR mutation panels or second-tier CFTR panel followed by third-tier sequencing?

PubMed

Currier, Robert J; Sciortino, Stan; Liu, Ruiling; Bishop, Tracey; Alikhani Koupaei, Rasoul; Feuchtbaum, Lisa

2017-10-01

PurposeThe purpose of this study was to model the performance of several known two-tier, predefined mutation panels and three-tier algorithms for cystic fibrosis (CF) screening utilizing the ethnically diverse California population.MethodsThe cystic fibrosis transmembrane conductance regulator (CFTR) mutations identified among the 317 CF cases in California screened between 12 August 2008 and 18 December 2012 were used to compare the expected CF detection rates for several two- and three-tier screening approaches, including the current California approach, which consists of a population-specific 40-mutation panel followed by third-tier sequencing when indicated.ResultsThe data show that the strategy of using third-tier sequencing improves CF detection following an initial elevated immunoreactive trypsinogen and detection of only one mutation on a second-tier panel.ConclusionIn a diverse population, the use of a second-tier panel followed by third-tier CFTR gene sequencing provides a better detection rate for CF, compared with the use of a second-tier approach alone, and is an effective way to minimize the referrals of CF carriers for sweat testing. Restricting screening to a second-tier testing to predefined mutation panels, even broad ones, results in some missed CF cases and demonstrates the limited utility of this approach in states that have diverse multiethnic populations.

Cystic fibrosis research topics featured at the 14th ECFS Basic Science Conference: Chairman's summary.

PubMed

Mall, Marcus A; Hwang, Tzyh-Chang; Braakman, Ineke

2018-03-01

In recent years, tremendous progress has been made in the development of novel drugs targeting the basic defect in patients with cystic fibrosis (CF). This breakthrough is based on a solid foundation of knowledge on CFTR's function in health and how mutations in CFTR cause CF multi-organ disease. This knowledge has been collected and continuously expanded by an active and persistent CF research community and has paved the way for precision medicine for CF. Since 2004, the European Cystic Fibrosis Society (ECFS) has held an annual Basic Science Conference that has evolved as an international forum for interdisciplinary discussion of hot topics and unsolved questions related to CF research. This Special Issue reviews CF research topics featured at the 14th ECFS Basic Science Conference and provides an up-to-date overview of recent progress in our understanding of CFTR structure and function, disease mechanisms implicated in airway mucus plugging, inflammation and abnormal host-pathogen interactions, and advancements with enhanced cell and animal model systems and breakthrough therapies directed at mutant CFTR or alternative targets. In addition, this Special Issue also identifies a number of fundamental questions and hurdles that still have to be overcome to realize the full potential of precision medicine and develop transformative therapies for all patients with CF. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

Sleep and Behavior in Cross-Fostering Rats: Developmental and Sex Aspects.

PubMed

Santangeli, Olena; Lehtikuja, Henna; Palomäki, Eeva; Wigren, Henna-Kaisa; Paunio, Tiina; Porkka-Heiskanen, Tarja

2016-12-01

Adverse early-life events induce behavioral psychopathologies and sleep changes in adulthood. In order to understand the molecular level mechanisms by which the maltreatment modifies sleep, valid animal models are needed. Changing pups between mothers at early age (cross-fostering) may satisfyingly model adverse events in human childhood. Cross-fostering (CF) was used to model mild early-life stress in male and female Wistar rats. Behavior and BDNF gene expression in the basal forebrain (BF), cortex, and hypothalamus were assessed during adolescence and adulthood. Spontaneous sleep, sleep homeostasis, and BF extracellular adenosine levels were assessed in adulthood. CF rats demonstrated increased number of REM sleep onsets in light and dark periods of the day. Total REM and NREM sleep duration was also increased during the light period. While sleep homeostasis was not severely affected, basal level of adenosine in the BF of both male and female CF rats was lower than in controls. CF did not lead to considerable changes in behavior. Even when the consequences of adverse early-life events are not observed in tests for anxiety and depression, they leave a molecular mark in the brain, which can act as a vulnerability factor for psychopathologies in later life. Sleep is a sensitive indicator for even mild early-life stress. © 2016 Associated Professional Sleep Societies, LLC.

Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis

PubMed Central

Sun, Xingshen; Sui, Hongshu; Fisher, John T.; Yan, Ziying; Liu, Xiaoming; Cho, Hyung-Ju; Joo, Nam Soo; Zhang, Yulong; Zhou, Weihong; Yi, Yaling; Kinyon, Joann M.; Lei-Butters, Diana C.; Griffin, Michelle A.; Naumann, Paul; Luo, Meihui; Ascher, Jill; Wang, Kai; Frana, Timothy; Wine, Jeffrey J.; Meyerholz, David K.; Engelhardt, John F.

2010-01-01

Cystic fibrosis (CF) is a recessive disease that affects multiple organs. It is caused by mutations in CFTR. Animal modeling of this disease has been challenging, with species- and strain-specific differences in organ biology and CFTR function influencing the emergence of disease pathology. Here, we report the phenotype of a CFTR-knockout ferret model of CF. Neonatal CFTR-knockout ferrets demonstrated many of the characteristics of human CF disease, including defective airway chloride transport and submucosal gland fluid secretion; variably penetrant meconium ileus (MI); pancreatic, liver, and vas deferens disease; and a predisposition to lung infection in the early postnatal period. Severe malabsorption by the gastrointestinal (GI) tract was the primary cause of death in CFTR-knockout kits that escaped MI. Elevated liver function tests in CFTR-knockout kits were corrected by oral administration of ursodeoxycholic acid, and the addition of an oral proton-pump inhibitor improved weight gain and survival. To overcome the limitations imposed by the severe intestinal phenotype, we cloned 4 gut-corrected transgenic CFTR-knockout kits that expressed ferret CFTR specifically in the intestine. One clone passed feces normally and demonstrated no detectable ferret CFTR expression in the lung or liver. The animals described in this study are likely to be useful tools for dissecting CF disease pathogenesis and developing treatments. PMID:20739752

Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis.

PubMed

Sun, Xingshen; Sui, Hongshu; Fisher, John T; Yan, Ziying; Liu, Xiaoming; Cho, Hyung-Ju; Joo, Nam Soo; Zhang, Yulong; Zhou, Weihong; Yi, Yaling; Kinyon, Joann M; Lei-Butters, Diana C; Griffin, Michelle A; Naumann, Paul; Luo, Meihui; Ascher, Jill; Wang, Kai; Frana, Timothy; Wine, Jeffrey J; Meyerholz, David K; Engelhardt, John F

2010-09-01

Cystic fibrosis (CF) is a recessive disease that affects multiple organs. It is caused by mutations in CFTR. Animal modeling of this disease has been challenging, with species- and strain-specific differences in organ biology and CFTR function influencing the emergence of disease pathology. Here, we report the phenotype of a CFTR-knockout ferret model of CF. Neonatal CFTR-knockout ferrets demonstrated many of the characteristics of human CF disease, including defective airway chloride transport and submucosal gland fluid secretion; variably penetrant meconium ileus (MI); pancreatic, liver, and vas deferens disease; and a predisposition to lung infection in the early postnatal period. Severe malabsorption by the gastrointestinal (GI) tract was the primary cause of death in CFTR-knockout kits that escaped MI. Elevated liver function tests in CFTR-knockout kits were corrected by oral administration of ursodeoxycholic acid, and the addition of an oral proton-pump inhibitor improved weight gain and survival. To overcome the limitations imposed by the severe intestinal phenotype, we cloned 4 gut-corrected transgenic CFTR-knockout kits that expressed ferret CFTR specifically in the intestine. One clone passed feces normally and demonstrated no detectable ferret CFTR expression in the lung or liver. The animals described in this study are likely to be useful tools for dissecting CF disease pathogenesis and developing treatments.

7Li-induced reaction on natMo: A study of complete versus incomplete fusion

NASA Astrophysics Data System (ADS)

Kumar, Deepak; Maiti, Moumita; Lahiri, Susanta

2017-07-01

Background: Several investigations on the complete-incomplete fusion (CF-ICF) dynamics of α -cluster well-bound nuclei have been contemplated above the Coulomb barrier (˜4 -7 MeV/nucleon) in recent years. It is therefore expected to observe significant ICF over CF in the reactions induced by a weakly bound α -cluster nucleus at slightly above the barrier. Purpose: Study of the CF-ICF dynamics by measuring the populated residues in the weakly bound 7Li+natMo system at energies slightly above the Coulomb barrier to well above it. Method: In order to investigate CF-ICF in the loosely bound system, 7Li beam was bombarded on the natMo foils, separated by the aluminium (Al) catcher foils alternatively, within ˜3 -6.5 MeV/nucleon. Evaporation residues produced in each foil were identified by the off-line γ -ray spectrometry. Measured cross section data of the residues were compared with the theoretical model calculations based on the equilibrium (EQ) and pre-equilibrium (PEQ) reaction mechanisms. Results: The experimental cross section of Rh 101 m,100 ,99 m,97 ,Ru,9597,Tc 99 m,96 ,95 ,94 ,93 m+g , and 93mMo residues measured at various projectile energies were satisfactorily reproduced by the simplified coupled channel approach in comparison to single barrier penetration model calculation. Significant cross section enhancement in the α -emitting channels was observed compared to EQ and PEQ model calculations throughout observed energy region. The ICF process over CF was analyzed by comparing with EMPIRE. The increment of the incomplete fusion fraction was observed with increasing projectile energies. Conclusions: Theoretical model calculations reveal that the compound reaction mechanism is the major contributor to the production of residues in 7Li+natMo reaction. Theoretical evaluations substantiate the contribution of ICF over the CF in α -emitting channels. EMPIRE estimations shed light on its predictive capability of cross sections of the residues from the heavy-ion induced reactions.

Implications of Requiring New Production of Older Aircraft Types (less than 75,000 pounds) to Meet Amended Noise Standards.

DTIC Science & Technology

1980-06-01

ratio CF700 engine, do not qualify, but in each case the producer has plans for, or is delivering a model using the TFE731 engine that does qualify. CF700...the size range, namely, the Learjets using the CJ610 engine and the Gulfstream 3 using the Spey. All medium-sized jets using the TFE731 are quieter...very few engines available for aircraft in each size range: the JT15 and CJ610 for small aircraft, the CF700, ATF3, and TFE731 for medium aircraft and

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...

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.

Magnetism in californium

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

Moore, J.R.

1988-03-01

A SQUID-based magnetic susceptometer has been constructed for studying small radioactive samples at temperatures below 350 K and in magnetic fields up to 50 kilogauss. The device has been used to study californium (element 98) in a number of solid-state forms: the dhcp metal, several oxides (Cf/sub 2/O/sub 3/ in both the bcc and monoclinic structures, Cf/sub 7/O/sub 12/, CfO/sub 2/ and BaCfO/sub 3/), several monopnictides (CfN, CfAs and CfSb) and the trichloride (in both the hexagonal and orthorhombic structures). All of these materials were studied in polycrystalline form, and hexagonal CfCl/sub 3/ was studied in single-crystal form as well.more » The susceptometer has the sensitivity to measure samples containing less than 10 micrograms of californium. The magnetic susceptibilities of all of the californium materials at temperatures above about 100 K are described well by the Curie-Weiss relationship. This behavior is consistent with the assumption that the magnetic 5f electrons are localized and that the paramagnetic behavior can be interpreted in terms of the properties of the free ion. The measured values of the effective paramagnetic moment, ..mu../sub eff/, for all the californium materials that were studied are reasonably consistent with theoretical values based on intermediate coupling models. All of the californium materials showed some indications of cooperative magnetic effects. The dhcp metal was observed to order ferromagnetically at 52 K, and all of the californium compounds studied showed signs of antiferromagnetic ordering, mostly at temperatures below 25 K. 91 refs., 50 figs., 19 tabs.« less

Functional genomic responses to cystic fibrosis transmembrane conductance regulator (CFTR) and CFTR(delta508) in the lung.

PubMed

Xu, Yan; Liu, Cong; Clark, Jean C; Whitsett, Jeffrey A

2006-04-21

Cystic fibrosis (CF), a common lethal pulmonary disorder in Caucasians, is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) that disturbs fluid homeostasis and host defense in target organs. The effects of CFTR and delta508-CFTR were assessed in transgenic mice that 1) lack CFTR expression (Cftr-/-); 2) express the human delta508 CFTR (CFTR(delta508)); 3) overexpress the normal human CFTR (CFTR(tg)) in respiratory epithelial cells. Genes were selected from Affymetrix Murine Gene-Chips analysis and subjected to functional classification, k-means clustering, promoter cis-elements/modules searching, literature mining, and pathway exploring. Genomic responses to Cftr-/- were not corrected by expression of CFTR(delta508). Genes regulating host defense, inflammation, fluid and electrolyte transport were similarly altered in Cftr-/- and CFTR(delta508) mice. CFTR(delta508) induced a primary disturbance in expression of genes regulating redox and antioxidant systems. Genomic responses to CFTR(tg) were modest and were not associated with lung pathology. CFTR(tg) and CFTR(delta508) induced genes encoding heat shock proteins and other chaperones but did not activate the endoplasmic reticulum-associated degradation pathway. RNAs encoding proteins that directly interact with CFTR were identified in each of the CFTR mouse models, supporting the hypothesis that CFTR functions within a multiprotein complex whose members interact at the level of protein-protein interactions and gene expression. Promoters of genes influenced by CFTR shared common regulatory elements, suggesting that their co-expression may be mediated by shared regulatory mechanisms. Genes and pathways involved in the response to CFTR may be of interest as modifiers of CF.

In Vivo Airway Surface Liquid Cl− Analysis with Solid-State Electrodes

PubMed Central

Caldwell, Ray A.; Grubb, Barbara R.; Tarran, Robert; Boucher, Richard C.; Knowles, Michael R.; Barker, Pierre M.

2002-01-01

The pathogenesis of cystic fibrosis (CF) airways disease remains controversial. Hypotheses that link mutations in CFTR and defects in ion transport to CF lung disease predict that alterations in airway surface liquid (ASL) isotonic volume, or ion composition, are critically important. ASL [Cl−] is pivotal in discriminating between these hypotheses, but there is no consensus on this value given the difficulty in measuring [Cl−] in the “thin” ASL (∼30 μm) in vivo. Consequently, a miniaturized solid-state electrode with a shallow depth of immersion was constructed to measure ASL [Cl−] in vivo. In initial experiments, the electrode measured [Cl−] in physiologic salt solutions, small volume (7.6 μl) test solutions, and in in vitro cell culture models, with ≥93% accuracy. Based on discrepancies in reported values and/or absence of data, ASL Cl− measurements were made in the following airway regions and species. First, ASL [Cl−] was measured in normal human nasal cavity and averaged 117.3 ± 11.2 mM (n = 6). Second, ASL [Cl−] measured in large airway (tracheobronchial) regions were as follows: rabbit trachea and bronchus = 114.3 ± 1.8 mM; (n = 6) and 126.9 ± 1.7 mM; (n = 3), respectively; mouse trachea = 112.8 ± 4.2 mM (n = 13); and monkey bronchus = 112.3 ± 10.9 mM (n = 3). Third, Cl− measurements were made in small (1–2 mm) diameter airways of the rabbit (108.3 ± 7.1 mM, n = 5) and monkey (128.5 ± 6.8 mM, n = 3). The measured [Cl−], in excess of 100 mM throughout all airway regions tested in multiple species, is consistent with the isotonic volume hypothesis to describe ASL physiology. PMID:11773234

Immune mediators associated to male infertility in a mouse model of DNA immunization with the sperm protease proacrosin.

PubMed

Russi, Romina; García, María Inés; Vignatti, Paulina; Veiga, María Florencia; Vazquez-Levin, Mónica Hebe; Veaute, Carolina

2016-11-01

The immune response has relevant physiological functions both in the male and female reproductive system, and must be tightly controlled to achieve a successful pregnancy. Several immune factors have been related to infertility, among them humoral and cellular immune responses triggered by sperm antigens. The present study was aimed at evaluating the immune profile induced by DNA immunization against the sperm protease proacrosin in CF1 male mice and its effect upon fertility. Immunized animals exhibited higher anti-proacrosin antibodies levels than controls (indirect ELISA), both in serum (p<0.01) and in seminal vesicle fluid (SVF; p<0.05). IgG2a levels were higher than IgG1 in serum (p<0.01) and similar in SVF. IL-10 and TGF-β1 mRNA levels were lower in testis (p<0.05), whereas TNF-α and IFN-γ transcript levels were increased in SV tissue (p<0.05). Immunized mice showed a trend toward higher IFN-γ concentration in serum and SVF than controls. Male fertility rate was diminished in immunized mice (p<0.01) and inversely correlated with serum and SVF anti-proacrosin IgG levels (p<0.001). Immunized animals also had fewer pups born than controls (p<0.01). To our knowledge, this is the first report on DNA immunization done in CF1 mice. Injection of proacrosin DNA induces an immune response in the male reproductive tract characterized by high levels of specific antibodies and cytokine changes. These factors may alter the crucial balance of the genital tract microenvironment required for adequate fertilization and pregnancy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Unlocking the coral calcification process: Insights from boron isotope measurements and a skeletal growth model

NASA Astrophysics Data System (ADS)

Mollica, N. R.; Guo, W.; Cohen, A. L.; Huang, K. F.; Foster, G. L.; Donald, H.; Solow, A.

2017-12-01

Carbonate skeletons of scleractinian corals are important archives of ocean climate and environmental change. However, corals don't accrete their skeletons directly from ambient seawater, but from a calcifying fluid whose composition is strongly regulated. There is mounting evidence that the carbonate chemistry of this calcifying fluid significantly impacts the amount of carbonate the coral can precipitate, which in turn affects the geochemical composition of the skeleton produced. However the mechanistic link between calcifying fluid (cf) chemistry, particularly the up-regulation of pHcf and thereby aragonite saturation state (Ωcf), and coral calcification is not well understood. We explored this link by combining boron isotope measurements with in situ measurements of seawater temperature, salinity, and DIC to estimate Ωcf of nine Porites corals from four Pacific reefs. Associated calcification rates were quantified for each core via CT scanning. We do not observe a relationship between calcification rates and Ωcf or Ωsw. Instead, when we deconvolve calcification into linear extension and skeletal density, a significant correlation is observed between density and Ωcf, and also Ωsw while extension does not correlate with either. These observations are consistent with the two-step model of coral calcification, in which skeleton is secreted in two distinct phases: vertical extension creating new skeletal elements, followed by lateral thickening of existing elements that are covered by living tissue. We developed a numerical model of Porites skeletal growth that builds on this two-step model and links skeletal density with the external seawater environment via its influence on the chemistry of coral calcifying fluid. We validated the model using existing coral skeletal datasets from six Porites species collected across five reef sites, and quantified the effects of each seawater parameter (e.g. temperature, pH, DIC) on skeletal density. Our findings illustrate the sensitivity of the second phase of coral calcification to the carbonate chemistry of the calcifying fluid, and support previous coral proxy system modelling efforts by validating the two-step growth model on annual and seasonal scales.

A novel method for blood volume estimation using trivalent chromium in rabbit models.

PubMed

Baby, Prathap Moothamadathil; Kumar, Pramod; Kumar, Rajesh; Jacob, Sanu S; Rawat, Dinesh; Binu, V S; Karun, Kalesh M

2014-05-01

Blood volume measurement though important in management of critically ill-patients is not routinely estimated in clinical practice owing to labour intensive, intricate and time consuming nature of existing methods. The aim was to compare blood volume estimations using trivalent chromium [(51)Cr(III)] and standard Evans blue dye (EBD) method in New Zealand white rabbit models and establish correction-factor (CF). Blood volume estimation in 33 rabbits was carried out using EBD method and concentration determined using spectrophotometric assay followed by blood volume estimation using direct injection of (51)Cr(III). Twenty out of 33 rabbits were used to find CF by dividing blood volume estimation using EBD with blood volume estimation using (51)Cr(III). CF is validated in 13 rabbits by multiplying it with blood volume estimation values obtained using (51)Cr(III). The mean circulating blood volume of 33 rabbits using EBD was 142.02 ± 22.77 ml or 65.76 ± 9.31 ml/kg and using (51)Cr(III) was estimated to be 195.66 ± 47.30 ml or 89.81 ± 17.88 ml/kg. The CF was found to be 0.77. The mean blood volume of 13 rabbits measured using EBD was 139.54 ± 27.19 ml or 66.33 ± 8.26 ml/kg and using (51)Cr(III) with CF was 152.73 ± 46.25 ml or 71.87 ± 13.81 ml/kg (P = 0.11). The estimation of blood volume using (51)Cr(III) was comparable to standard EBD method using CF. With further research in this direction, we envisage human blood volume estimation using (51)Cr(III) to find its application in acute clinical settings.

Emissions of Tetrafluoromethane (CF4) and Hexafluoroethane (C2F6) from East Asian Aluminum and Semiconductor Industries

NASA Astrophysics Data System (ADS)

Kim, J.; Li, S.; Muhle, J.; Fang, X.; Manning, A. J.; Arnold, T.; Park, S.; Park, M.; Saito, T.; Yokouchi, Y.; Stohl, A.; Weiss, R. F.; Kim, K.

2013-12-01

Tetrafluoromethane (CF4) and Hexafluoroethane (C2F6) are among the most potent greenhouse gases (GHGs), with atmospheric lifetimes of 50,000 and 10,000 years and 100-year Global Warming Potentials of 7,490 and 12,200, respectively. The Chinese aluminum smelting (AL) industry, accounting for 39% of the global aluminum production in 2010, has become a significant emitter of these compounds to the atmosphere, . The AL industry has estimated its Chinese emissions averaged over 2008-2010 at 1.4 Gg/yr of CF4 and 0.06 Gg/yr of C2F6. In this study we combine East Asian measurements of C2F6 at Gosan (Jeju Island, Korea), Hateruma, and Ochi-Ishi (Japan) and of CF4 at Gosan, using inversion techniques and two Lagrangian particle dispersion models (FLEXPART and NAME), to estimate the emissions of these two compounds from China and East Asia. Our results yield total emissions from China for the 2008-2010 period of approximately 4 × 0.5 Gg/yr for CF4 and 0.8 × 0.1 Gg/yr for C2F6. These results may be reconciled if emissions of these compounds from China's semiconductor (SC) industry are larger than currently estimated. However, evidence presented in the analysis of the inversion results and in the C2F6/CF4 emission ratios observed for China suggest that China's AL industry emissions are likely to be the dominant source of the discrepancy between reported emissions and those inferred from atmospheric measurements. As the AL and SC industries evolve toward new manufacturing technologies that reduce GHG emissions, continued and improved atmospheric measurements and modeling in this region will be useful in assessing the effectiveness of these changes.

Preparation of new crosslinking agents and additives for use in polymer electrolyte membranes (PEMs) for fuel cell applications

NASA Astrophysics Data System (ADS)

Zhou, Yangliu

The most commonly used proton conductive membrane in polymer electrolyte membrane fuel cells (PEMFC) and direct methanol fuel cells (DMFC) studies to date is DuPont's NafionRTM, which is a perfluorinated copolymer of tetrafluoroethylene (TFE) and perfluorovinyl ether with a pendant sulfonic acid group. A focus of this work is to find ways to improve the performance of NafionRTM membranes. Crosslinking the TFE chains of fluorinated ionomeric copolymers to improve their thermal and mechanical stability is a proven route to this goal. A straightforward synthetic route to perfluorinated divinyl ethers of the formula CF2=CFO(CF 2)3[OCF(CF3)CF2]mOCF=CF 2 (m = 0-1) has been demonstrated. The compounds CF2=CFO(CF 2)3OCF=CF2 and CF2=CFO(CF2) 3OCF(CF3)CF2OCF=CF2 were prepared and characterized by GC-MS, 13C and 19F NMR, and gas-IR spectroscopy. Synthetic routes to fluorosulfato-tetrafluoropropionyl fluoride [FSO3CF2CF2C(O)F] and difluoromalonyl difluoride [F(O)CCF2C(O)F] with improved yields were found. The second focus of the dissertation was the development of fluorous triarylphosphines for use as new doping materials for the modification of NafionRTM membranes and for use as ligands in catalysts for biphasic catalysis. The synthesis and characterization of a series of new polyhexafluoropropylene oxide derivatives for preparation of fluorous triarylphosphines and phosphonium salts was studied, such as F[CF(CF3)CF2O] 4CF(CF3)CH2CH2I, F[CF(CF3)CF 2O]4CF(CF3)CH=CH2, F[CF(CF3)CF 2O]4CF(CF3) CH2CH2C6H5, and F[CF(CF 3)CF2O]4CF(CF3)CH2CH 2C6H4Br. In a separate study, the photochlorination of 2,2,3,3-tetrafluoro-1-propanol (HCF2CF2CH2OH) and 2,2,3,3-tetrafluoropropyl 2,2,3,3-tetrafluoropropionate [HCF2CF2C(O)OCH2 CF2CF2H] with super diazo blue light (lambda max = 420 nm) were investigated. The photochemical products are different from those obtained under mercury light (lambda = 253.7nm). A new compound ClCF2CF2C(O)OC(H)ClCF2CF2Cl was prepared and characterized by GC-MS, elemental analysis, 1H, 13C and 19F NMR, and gas-IR spectroscopy.

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 or apoptosis of cells in acute exercise settings. Recently, rapid DNA release mechanisms of activated immune-competent cells like NETosis (pathogen-induced cell death including the release of neutrophil extracellular traps [NETs]) have been discovered. cfDNA accumulations might comprise a similar kind of cell death including trap formation or an active release of cfDNA. Just like chronic diseases, chronic high-intensity resistance training protocols induced persistent increases of cfDNA levels. Chronic, strenuous exercise protocols, either long-duration endurance exercise or regular high-intensity workouts, induce chronic inflammation that might lead to a slow, constant release of DNA. This could be due to mechanisms of cell death like apoptosis or necrosis. Yet, it has neither been implicated nor proven sufficiently whether cfDNA can serve as a marker for overtraining. The relevance of cfDNA with regard to overtraining status, performance level, and the degree of physical exhaustion still remains unclear. Longitudinal studies are required that take into account standardized and controlled exercise, serial blood sampling, and large and homogeneous cohorts of different athletic achievement. Furthermore, it is important to establish standardized laboratory procedures for the measurement of genomic cfDNA concentrations by quantitative real-time polymerase chain reaction (PCR). We introduce a new hypothesis based on acute exercise and chronic exposure to stress, and rapid active and passive chronic release of cfDNA fragments into the circulation.

Modelling Water Flow through Paddy Soils under Alternate Wetting and Drying Irrigation Practice

NASA Astrophysics Data System (ADS)

Shekhar, S.; Mailapalli, D. R.; Das, B. S.; Raghuwanshi, N. S.

2017-12-01

Alternate wetting and drying (AWD) irrigation practice in paddy cultivation requires an optimum soil moisture stress (OSMS) level at which irrigation water savings can be maximized without compromising the yield reduction. Determining OSMS experimentally is challenging and only possible with appropriate modeling tools. In this study, field experiments on paddy were conducted in thirty non-weighing type lysimeters during dry seasons of 2016 and 2017. Ten plots were irrigated using continuous flooding (CF) and the rest were irrigated with AWD practice at 40mb and 75mb soil moisture stress levels. Depth of ponding and soil suction at 10, 40 and 70 cm from the soil surface were measured daily from all lysimeter plots. The measured field data were used in calibration and validation of Hydrus-1D model and simulated the water flow for both AWD and CF plots. The Hydrus-1D is being used to estimate OSMS for AWD practice and compared the seasonal irrigation water input and deep percolation losses with CF practice.

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.

Gas exchanges in children with cystic fibrosis or primary ciliary dyskinesia: A retrospective study.

PubMed

Fuger, Marilyn; Aupiais, Camille; Thouvenin, Guillaume; Taytard, Jessica; Tamalet, Aline; Escudier, Estelle; Boizeau, Priscilla; Corvol, Harriet; Beydon, Nicole

2018-05-01

Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) both entail bronchiectasis and pulmonary impairment as measured using spirometry, during childhood. We aimed at looking whether blood gas exchanges progressed differently between CF and PCD children in a retrospective study of repeated measurements. Comparisons between groups (Wilcoxon-Mann-Whitney and Chi-squared tests) and a mixed linear model, adjusted for age, evaluated associations between diseases and PaO 2 , PaCO 2, or PaO 2- PaCO 2 ratio. Among 42 PCD and 73 CF children, 62% and 59% had respectively bronchiectasis (P = 0.75). Spirometry and blood gases were similar at inclusion (PaO 2 median [IQR] PCD -1.80 [-3.40; -0.40]; CF -1.80 [-4.20; 0.60] z-scores; P = 0.72). PaO 2 and PaO 2 -PaCO 2 ratio similarly and significantly decreased with age in both groups (P < 0.01) whereas PaCO 2 increased more in CF (P = 0.02) remaining within the range of normal (except for one child). To conclude, gas exchange characteristics, similarly initially impaired in PCD and CF children, tended to less deteriorate with time in PCD children who could benefit from an early diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Coping styles in adults with cystic fibrosis: implications for emotional and social quality of life.

PubMed

Mc Hugh, Rachel; Mc Feeters, Danielle; Boyda, David; O'Neill, Siobhan

2016-01-01

As life expectancy increases, interest has grown surrounding the factors that may influence quality of life (QOL) for people with cystic fibrosis (CF). The aim of the current study was to examine which specific coping styles were positively or negatively associated with social and emotional QOL in a CF sample. One hundred and twenty-two respondents aged 18 and over were recruited through an online support group. Respondents completed the 'CF Questionnaire-Revised (CFQ-R)' and the 'Brief COPE'. The CFQ-R is a disease-specific instrument designed to measure the impact of CF on nine QOL domains and the Brief COPE is a 28 item questionnaire which assesses 14 coping scales. A multivariate regression model revealed that higher substance abuse and disengagement was associated with lower emotional QOL whereas greater use of religion, instrumental coping and acceptance was positively associated with emotional QOL. Active coping was linked to better social QOL and a negative association was reported between distraction coping with both emotional and social domains. Given the burden of CF, ascertaining which factors enhance or diminish emotion and social well-being is now an integral component of QOL research. The current findings may therefore have value in informing clinical interventions which aim to cater for the psychological needs of individuals with CF.

Neutrophil elastase-mediated increase in airway temperature during inflammation.

PubMed

Schmidt, Annika; Belaaouaj, Azzaq; Bissinger, Rosi; Koller, Garrit; Malleret, Laurette; D'Orazio, Ciro; Facchinelli, Martino; Schulte-Hubbert, Bernhard; Molinaro, Antonio; Holst, Otto; Hammermann, Jutta; Schniederjans, Monika; Meyer, Keith C; Damkiaer, Soeren; Piacentini, Giorgio; Assael, Baroukh; Bruce, Kenneth; Häußler, Susanne; LiPuma, John J; Seelig, Joachim; Worlitzsch, Dieter; Döring, Gerd

2014-12-01

How elevated temperature is generated during airway infections represents a hitherto unresolved physiological question. We hypothesized that innate immune defence mechanisms would increase luminal airway temperature during pulmonary infection. We determined the temperature in the exhaled air of cystic fibrosis (CF) patients. To further test our hypothesis, a pouch inflammatory model using neutrophil elastase-deficient mice was employed. Next, the impact of temperature changes on the dominant CF pathogen Pseudomonas aeruginosa growth was tested by plating method and RNAseq. Here we show a temperature of ~38°C in neutrophil-dominated mucus plugs of chronically infected CF patients and implicate neutrophil elastase:α1-proteinase inhibitor complex formation as a relevant mechanism for the local temperature rise. Gene expression of the main pathogen in CF, P. aeruginosa, under anaerobic conditions at 38°C vs 30°C revealed increased virulence traits and characteristic cell wall changes. Neutrophil elastase mediates increase in airway temperature, which may contribute to P. aeruginosa selection during the course of chronic infection in CF. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Structural and electrical properties of nickel substituted cadmium ferrite

NASA Astrophysics Data System (ADS)

Chethan, B.; Raj Prakash, H. G.; Vijayakumari, S. C.; Ravikiran, Y. T.

2018-05-01

Spinal nano-sized Cadmium ferrite (CD) and Nickel substituted cadmium ferrite (NSCF) were fabricated by sol-gel auto combustion method. The formation of spinal structure of ferrite materials was confirmed by X-ray diffraction (XRD) analysis. The crystallites size of CF and NSCF as determined by Scherrer's formula were found to be 24.73 nm and 17.70 nm respectively. comparative study of Fourier transform infrared spectroscopy (FTIR) of CF and NSCF revealed tetrahedral absorption bands shifted slightly towards higher frequency where as octahedral bands shifted towards lower frequency side confirming interfacial interaction between Ni and CF. The AC conductivity (σ), loss tangent (tan δ) and complex plane impedance plots for both CF and NSCF are determined at various frequencies ranging from 50 kHz to 5 MHz and comparatively analyzed. The increase in AC conductivity of the NSCF nano particles as compared to CF was explained in the light of hopping model. The impedance measurement of NSCF show presence of a semi-circle corresponding to the grain boundary resistance and hence shows that the conductivity takes place largely through grain boundaries.

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.

Disease-modifying genetic factors in cystic fibrosis.

PubMed

Marson, Fernando A L

2018-05-01

To compile data from the past 10 years regarding the role of modifying genes in cystic fibrosis (CF). CF is a model disease for understanding of the action of modifying genes. Although it is a monogenic (CFTR) autosomal recessive disease, CF presents with wide phenotypic variability. In CF, variability occurs with different intensity among patients by each organ, being organ-specific, resulting from the mutual interaction of environmental and genetic factors, including CFTR mutations and various other genes, most of which are associated with inflammatory processes. In individuals, using precision medicine, gene modification studies have revealed individualized responses to drugs depending on particular CFTR mutations and modifying genes, most of which are alternative ion channels. Studies of modifying genes in CF allow: understanding of clinical variability among patients with the same CFTR genotype; evaluation of precision medicine; understanding of environmental and genetic effects at the organ level; understanding the involvement of genetic variants in inflammatory responses; improvements in genetic counseling; understanding the involvement of genetic variants in inflammatory responses in lung diseases, such as asthma; and understanding the individuality of the person with the disease.

Effect of fiber-matrix adhesion on the creep behavior of CF/PPS composites: temperature and physical aging characterization

NASA Astrophysics Data System (ADS)

Motta Dias, M. H.; Jansen, K. M. B.; Luinge, J. W.; Bersee, H. E. N.; Benedictus, R.

2016-06-01

The influence of fiber-matrix adhesion on the linear viscoelastic creep behavior of `as received' and `surface modified' carbon fibers (AR-CF and SM-CF, respectively) reinforced polyphenylene sulfide (PPS) composite materials was investigated. Short-term tensile creep tests were performed on ±45° specimens under six different isothermal conditions, 40, 50, 60, 65, 70 and 75 °C. Physical aging effects were evaluated on both systems using the short-term test method established by Struik. The results showed that the shapes of the curves were affected neither by physical aging nor by the test temperature, allowing then superposition to be made. A unified model was proposed with a single physical aging and temperature-dependent shift factor, a_{T,te}. It was suggested that the surface treatment carried out in SM-CF/PPS had two major effects on the creep response of CF/PPS composites at a reference temperature of 40 °C: a lowering of the initial compliance of about 25 % and a slowing down of the creep response of about 1.1 decade.

A computer model of the pediatric circulatory system for testing pediatric assist devices.

PubMed

Giridharan, Guruprasad A; Koenig, Steven C; Mitchell, Michael; Gartner, Mark; Pantalos, George M

2007-01-01

Lumped parameter computer models of the pediatric circulatory systems for 1- and 4-year-olds were developed to predict hemodynamic responses to mechanical circulatory support devices. Model parameters, including resistance, compliance and volume, were adjusted to match hemodynamic pressure and flow waveforms, pressure-volume loops, percent systole, and heart rate of pediatric patients (n = 6) with normal ventricles. Left ventricular failure was modeled by adjusting the time-varying compliance curve of the left heart to produce aortic pressures and cardiac outputs consistent with those observed clinically. Models of pediatric continuous flow (CF) and pulsatile flow (PF) ventricular assist devices (VAD) and intraaortic balloon pump (IABP) were developed and integrated into the heart failure pediatric circulatory system models. Computer simulations were conducted to predict acute hemodynamic responses to PF and CF VAD operating at 50%, 75% and 100% support and 2.5 and 5 ml IABP operating at 1:1 and 1:2 support modes. The computer model of the pediatric circulation matched the human pediatric hemodynamic waveform morphology to within 90% and cardiac function parameters with 95% accuracy. The computer model predicted PF VAD and IABP restore aortic pressure pulsatility and variation in end-systolic and end-diastolic volume, but diminish with increasing CF VAD support.

Bacterial phospholipases C as vaccine candidate antigens against cystic fibrosis respiratory pathogens: the Mycobacterium abscessus model.

PubMed

Le Moigne, Vincent; Rottman, Martin; Goulard, Céline; Barteau, Benoît; Poncin, Isabelle; Soismier, Nathalie; Canaan, Stéphane; Pitard, Bruno; Gaillard, Jean-Louis; Herrmann, Jean-Louis

2015-04-27

Vaccine strategies represent one of the fighting answers against multiresistant bacteria in a number of clinical settings like cystic fibrosis (CF). Mycobacterium abscessus, an emerging CF pathogen, raises difficult therapeutic problems due to its intrinsic antibiotic multiresistance. By reverse vaccinology, we identified M. abscessus phospholipase C (MA-PLC) as a potential vaccine target. We deciphered here the protective response generated by vaccination with plasmid DNA encoding the MA-PLC formulated with a tetra functional block copolymer 704, in CF (ΔF508) mice. Protection was tested against aerosolized smooth and rough (hypervirulent) variants of M. abscessus. MA-PLC DNA vaccination (days 0, 21, 42) elicited a strong antibody response. A significant protective effect was obtained against aerosolized M. abscessus (S variant) in ΔF508 mice, but not in wild-type FVB littermates; similar results were observed when: (i) challenging mice with the "hypervirulent" R variant, and; (ii) immunizing mice with purified MA-PLC protein. High IgG titers against MA-PLC protein were measured in CF patients with M. abscessus infection; interestingly, significant titers were also detected in CF patients positive for Pseudomonas aeruginosa versus P. aeruginosa-negative controls. MA-PLC DNA- and PLC protein-vaccinated mice cleared more rapidly M. abscessus than β-galactosidase DNA- or PBS- vaccinated mice in the context of CF. PLCs could constitute interesting vaccine targets against common PLC-producing CF pathogens like P. aeruginosa. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modeling cystic fibrosis disease progression in patients with the rare CFTR mutation P67L.

PubMed

MacKenzie, Isobel E R; Paquette, Valerie; Gosse, Frances; George, Sheenagh; Chappe, Frederic; Chappe, Valerie

2017-05-01

The progression of cystic fibrosis (CF) in patients with the rare mutation P67L was examined to determine if it induced a milder form of CF compared to the common severe ΔF508 mutation. Parameters of lung function, level of bacterial infection, nutritional status and hospitalization were used to represent CF progression. Age at diagnosis and pancreatic status were used to assess CF presentation. Analysis of data from the CF Canada Registry collected over a 15-year period included 266 ΔF508/ΔF508 homozygote patients from CF clinics in Atlantic Canada and 26 compound heterozygote patients with the rare P67L mutation from clinics across Canada. Late age at diagnosis, high incidence of pancreatic sufficiency, maintained Body Mass Index (BMI) with age, delayed life-threatening bacterial infection, and fewer days in hospital were observed for P67L heterozygote patients included in this study. Although the decline of lung function did not differ from ΔF508 homozygotes, the fact that a greater proportion of P67L heterozygotes live to an older age suggests that lung function is not the primary factor determining CF progression for P67L heterozygote patients. The P67L mutation is associated with a mild disease, even when combined with the severe ΔF508 mutation. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Finite Element Analysis of the Endodontically-treated Maxillary Premolars restored with Composite Resin along with Glass Fiber Insertion in Various Positions.

PubMed

Navimipour, Elmira Jafari; Firouzmandi, Maryam; Mirhashemi, Fatemeh Sadat

2015-04-01

This study evaluated the effect of three methods of glass fiber insertion on stress distribution pattern and cusp movement of the root-filled maxillary premolars using finite element method (FEM) analysis. A three-dimensional (3 D) FEM model of a sound upper premolar tooth and four models of root-filled upper premolars with mesiocclusodistal (MOD) cavities were molded and restored with: (1) Composite resin only (NF); (2) Composite resin along with a ribbon of glass fiber placed in the occlusal third (OF); (3) Composite resin along with a ribbon of glass fiber placed circumferentially in the cervical third (CF), and (4) Composite resin along with occlusal and circumferential fibers (OCF). A static vertical load was applied to calculate the stress distributions. Structural analysis program by Solidworks were used for FEM analysis. Von-Mises stress values and cusp movements induced by occlusal loading were evaluated. Maximum Von-Mises stress of enamel occurred in sound tooth, followed by NF, CF, OF and OCF. Maximum Von-Mises stress of dentin occurred in sound tooth, followed by OF, OCF, CF and NF. Stress distribution patterns of OF and OCF were similar. Maximum overall stress values were concentrated in NF. Although stress distribution patterns of NF and CF were found as similar, CF showed lower stress values. Palatal cusp movement was more than buccal cusp in all of the models. The results of our study indicated that while the circumferential fiber had little effect on overall stress concentration, it provided a more favorable stress distribution pattern in cervical region. The occlusal fiber reduced the average stress in the entire structure but did not reduce cuspal movement. Incorporating glass fiber in composite restorations may alter the stress state within the structure depending on fiber position.

Chronic Stenotrophomonas maltophilia infection and mortality or lung transplantation in cystic fibrosis patients.

PubMed

Waters, Valerie; Atenafu, Eshetu G; Lu, Annie; Yau, Yvonne; Tullis, Elizabeth; Ratjen, Felix

2013-09-01

Chronic Stenotrophomonas maltophilia infection is an independent risk factor for severe pulmonary exacerbations in cystic fibrosis (CF) patients. The goal of this study was to determine the effect of chronic S. maltophilia infection on mortality and the need for lung transplantation in a longitudinal study of children and adults with CF. This was a cohort study of CF patients from the Hospital for Sick Children and St Michael's Hospital (Toronto, Canada) from 1997 to 2008. A Cox Regression model was used to estimate the hazard ratio (HR) to time of death or lung transplantation adjusting for age, gender, genotype, pancreatic status, CF related diabetes (CFRD), forced expiratory volume in 1 s (FEV1), body mass index, number of pulmonary exacerbations, Pseudomonas aeruginosa, Burkholderia cepacia complex, Aspergillus and chronic S. maltophilia infection. A total of 687 patients were followed over the 12 year study period; 95 patients underwent a lung transplantation (of which 26 died) and an additional 49 patients died (total 144 events). In a Cox Regression model adjusting for baseline FEV1, baseline infection with B. cepacia complex (HR 1.72, 95% CI 1.09-2.71) and baseline chronic S. maltophilia infection (HR 2.80, 95% CI 1.65-4.76) were significantly associated with death or lung transplant. However, in a time-varying model, infection with B. cepacia complex and chronic S. maltophilia infection were no longer significant. Baseline chronic S. maltophilia infection is associated with an almost three-fold increased risk of death or lung transplant in CF patients. It is still unclear, however, whether chronic S. maltophilia infection is simply a marker of severity of disease and ultimate mortality or whether it is causally related to disease progression. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Advances in a distributed approach for ocean model data interoperability

USGS Publications Warehouse

Signell, Richard P.; Snowden, Derrick P.

2014-01-01

An infrastructure for earth science data is emerging across the globe based on common data models and web services. As we evolve from custom file formats and web sites to standards-based web services and tools, data is becoming easier to distribute, find and retrieve, leaving more time for science. We describe recent advances that make it easier for ocean model providers to share their data, and for users to search, access, analyze and visualize ocean data using MATLAB® and Python®. These include a technique for modelers to create aggregated, Climate and Forecast (CF) metadata convention datasets from collections of non-standard Network Common Data Form (NetCDF) output files, the capability to remotely access data from CF-1.6-compliant NetCDF files using the Open Geospatial Consortium (OGC) Sensor Observation Service (SOS), a metadata standard for unstructured grid model output (UGRID), and tools that utilize both CF and UGRID standards to allow interoperable data search, browse and access. We use examples from the U.S. Integrated Ocean Observing System (IOOS®) Coastal and Ocean Modeling Testbed, a project in which modelers using both structured and unstructured grid model output needed to share their results, to compare their results with other models, and to compare models with observed data. The same techniques used here for ocean modeling output can be applied to atmospheric and climate model output, remote sensing data, digital terrain and bathymetric data.

Carbon/graphite fiber risk analysis and assessment study: Assessment of risk to the Lockheed Model L-1011 commercial transport aircraft

NASA Technical Reports Server (NTRS)

Daniledes, J.; Koch, J. R.

1980-01-01

The risk associated with the accidental release of carbon/graphite fibers (CF) from fires on commercial transport aircraft incorporating composite materials was assessed. Data are developed to evaluate the potential for CF damage to electrical and electronic equipment, assess the cost risk, and evaluate the hazard to continued operation. The subjects covered include identification of susceptible equipments, determination of infiltration transfer functions, analysis of airport operations, calculation of probabilities of equipment failures, assessment of the cost risk, and evaluation of the hazard to continued operation. The results show the risks associated with CF contamination are negligible through 1993.

Coralline algae elevate pH at the site of calcification under ocean acidification.

PubMed

Cornwall, Christopher E; Comeau, Steeve; McCulloch, Malcolm T

2017-10-01

Coralline algae provide important ecosystem services but are susceptible to the impacts of ocean acidification. However, the mechanisms are uncertain, and the magnitude is species specific. Here, we assess whether species-specific responses to ocean acidification of coralline algae are related to differences in pH at the site of calcification within the calcifying fluid/medium (pH cf ) using δ 11 B as a proxy. Declines in δ 11 B for all three species are consistent with shifts in δ 11 B expected if B(OH) 4 - was incorporated during precipitation. In particular, the δ 11 B ratio in Amphiroa anceps was too low to allow for reasonable pH cf values if B(OH) 3 rather than B(OH) 4 - was directly incorporated from the calcifying fluid. This points towards δ 11 B being a reliable proxy for pH cf for coralline algal calcite and that if B(OH) 3 is present in detectable proportions, it can be attributed to secondary postincorporation transformation of B(OH) 4 - . We thus show that pH cf is elevated during calcification and that the extent is species specific. The net calcification of two species of coralline algae (Sporolithon durum, and Amphiroa anceps) declined under elevated CO 2 , as did their pH cf . Neogoniolithon sp. had the highest pH cf , and most constant calcification rates, with the decrease in pH cf being ¼ that of seawater pH in the treatments, demonstrating a control of coralline algae on carbonate chemistry at their site of calcification. The discovery that coralline algae upregulate pH cf under ocean acidification is physiologically important and should be included in future models involving calcification. © 2017 John Wiley & Sons Ltd.

Transformation of carbon tetrachloride and chloroform by trichloroethene respiring anaerobic mixed cultures and supernatant.

PubMed

Vickstrom, Kyle E; Azizian, Mohammad F; Semprini, Lewis

2017-09-01

Carbon tetrachloride (CT) and chloroform (CF) were transformed in batch reactor experiments conducted with anaerobic dechlorinating cultures and supernatant (ADC + S) harvested from continuous flow reactors. The Evanite (EV) and Victoria/Stanford (VS) cultures, capable of respiring trichloroethene (TCE), 1,2-cis-dichloroethene (cDCE), and vinyl chloride (VC) to ethene (ETH), were grown in continuous flow reactors receiving an influent feed of saturated TCE (10 mM; 60 mEq) and formate (45 mM; 90 mEq) but no CT or CF. Cells and supernatant were harvested from the chemostats and inoculated into batch reactors at the onset of each experiment. CT transformation was complete following first order kinetics with CF, DCM and CS 2 as the measurable transformation products, representing 20-40% of the original mass of CT, with CO 2 likely the unknown transformation product. CF was transformed to DCM and likely CO 2 at an order of magnitude rate lower than CT, while DCM was not further transformed. An analytical first order model including multiple key reactions effectively simulated CT transformation, product formation and transformation, and provided reasonable estimates of transformation rate coefficients. Biotic and abiotic treatments indicated that CT was mainly transformed via abiotic processes. However, the presence of live cells was associated with the transformation of CF to DCM. In biotic tests both TCE and CT were simultaneously transformed, with TCE transformed to ETH and approximately 15-53% less CF formed via CT transformation. A 14-day exposure to CF (CF max  = 1.4 μM) reduced all rates of chlorinated ethene respiration by a factor of 10 or greater. Copyright © 2017 Elsevier Ltd. All rights reserved.

Breast-feeding and weaning practices in the DONALD study: age and time trends.

PubMed

Foterek, Kristina; Hilbig, Annett; Alexy, Ute

2014-03-01

Besides influencing short- and long-term health status, infant feeding practices are known to have an effect on later food preferences. This study aimed to identify present trends in breast-feeding duration and weaning practices with special focus on preparation methods of complementary food (CF), that is, homemade and commercial CF. In total, 1419 three-day weighed diet records collected between 2004 and 2012 from 366 children of the German DOrtmund Nutritional and Anthropometric Longitudinally Designed study ages 6 to 24 months were analysed. Full (n = 339) and total breast-feeding duration (n = 344) was collected by questionnaire. To investigate age and time trends, logistic regression and polynomial mixed regression models were used. Infants born between 2008 and 2012 were 3.3-fold less likely to be fully breast-fed for ≥4 months than those born before 2004 (P < 0.0001). Overall, 59.3% commercial, 21.1% homemade, and 19.6% combined CF was consumed by the study sample. Subjects with high commercial CF consumption (percentage of commercial CF > median 62%) were significantly older (P < 0.0001), showed shorter full and total breast-feeding duration (P < 0.0001), and were more likely to have mothers with a lower educational status (P = 0.01). Both commercial and homemade CF showed opposing, nonlinear age trends. No time trends could be found. Decreasing duration of full breast-feeding should encourage health care providers to further promote longer breast-feeding duration. With the constantly high consumption of commercial CF at all ages, nutritional adequacy of both homemade and commercial CF needs to be investigated closer, as does their long-term influence on health and dietary habits, for example, fruit and vegetable intake.

Mucous solids and liquid secretion by airways: studies with normal pig, cystic fibrosis human, and non-cystic fibrosis human bronchi

PubMed Central

Martens, Chelsea J.; Inglis, Sarah K.; Valentine, Vincent G.; Garrison, Jennifer; Conner, Gregory E.

2011-01-01

To better understand how airways produce thick airway mucus, nonvolatile solids were measured in liquid secreted by bronchi from normal pig, cystic fibrosis (CF) human, and non-CF human lungs. Bronchi were exposed to various secretagogues and anion secretion inhibitors to induce a range of liquid volume secretion rates. In all three groups, the relationship of solids concentration (percent nonvolatile solids) to liquid volume secretion rate was curvilinear, with higher solids concentration associated with lower rates of liquid volume secretion. In contrast, the secretion rates of solids mass and water mass as functions of liquid volume secretion rates exhibited positive linear correlations. The y-intercepts of the solids mass-liquid volume secretion relationships for all three groups were positive, thus accounting for the higher solids concentrations in airway liquid at low rates of secretion. Predictive models derived from the solids mass and water mass linear equations fit the experimental percent solids data for the three groups. The ratio of solids mass secretion to liquid volume secretion was 5.2 and 2.4 times higher for CF bronchi than for pig and non-CF bronchi, respectively. These results indicate that normal pig, non-CF human, and CF human bronchi produce a high-percent-solids mucus (>8%) at low rates of liquid volume secretion (≤1.0 μl·cm−2·h−1). However, CF bronchi produce mucus with twice the percent solids (∼8%) of pig or non-CF human bronchi at liquid volume secretion rates ≥4.0 μl·cm−2·h−1. PMID:21622844

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.

Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution

PubMed Central

Kevadiya, Bhavesh D.; Woldstad, Christopher; Ottemann, Brendan M.; Dash, Prasanta; Sajja, Balasrinivasa R.; Lamberty, Benjamin; Morsey, Brenda; Kocher, Ted; Dutta, Rinku; Bade, Aditya N.; Liu, Yutong; Callen, Shannon E.; Fox, Howard S.; Byrareddy, Siddappa N.; McMillan, JoEllyn M.; Bronich, Tatiana K.; Edagwa, Benson J.; Boska, Michael D.; Gendelman, Howard E.

2018-01-01

RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal models. METHODS: Europium (Eu3+)- doped cobalt ferrite (CF) dolutegravir (DTG)- loaded (EuCF-DTG) nanoparticles were synthesized then fully characterized based on their size, shape and stability. These were then used as platforms for nanoformulated drug biodistribution. RESULTS: Folic acid (FA) decoration of EuCF-DTG (FA-EuCF-DTG) nanoparticles facilitated macrophage targeting and sped drug entry across cell barriers. Macrophage uptake was higher for FA-EuCF-DTG than EuCF-DTG nanoparticles with relaxivities of r2 = 546 mM-1s-1 and r2 = 564 mM-1s-1 in saline, and r2 = 850 mM-1s-1 and r2 = 876 mM-1s-1 in cells, respectively. The values were ten or more times higher than what was observed for ultrasmall superparamagnetic iron oxide particles (r2 = 31.15 mM-1s-1 in saline) using identical iron concentrations. Drug particles were detected in macrophage Rab compartments by dual fluorescence labeling. Replicate particles elicited sustained antiretroviral responses. After parenteral injection of FA-EuCF-DTG and EuCF-DTG into rats and rhesus macaques, drug, iron and cobalt levels, measured by LC-MS/MS, magnetic resonance imaging, and ICP-MS were coordinate. CONCLUSION: We posit that these theranostic nanoprobes can assess LASER ART drug delivery and be used as part of a precision nanomedicine therapeutic strategy. PMID:29290806

Rationale and design of a randomized trial of home electronic symptom and lung function monitoring to detect cystic fibrosis pulmonary exacerbations: the early intervention in cystic fibrosis exacerbation (eICE) trial.

PubMed

Lechtzin, N; West, N; Allgood, S; Wilhelm, E; Khan, U; Mayer-Hamblett, N; Aitken, M L; Ramsey, B W; Boyle, M P; Mogayzel, P J; Goss, C H

2013-11-01

Acute pulmonary exacerbations are central events in the lives of individuals with cystic fibrosis (CF). Pulmonary exacerbations lead to impaired lung function, worse quality of life, and shorter survival. We hypothesized that aggressive early treatment of acute pulmonary exacerbation may improve clinical outcomes. Describe the rationale of an ongoing trial designed to determine the efficacy of home monitoring of both lung function measurements and symptoms for early detection and subsequent early treatment of acute CF pulmonary exacerbations. A randomized, non-blinded, multi-center trial in 320 individuals with CF aged 14 years and older. The study compares usual care to a twice a week assessment of home spirometry and CF respiratory symptoms using an electronic device with data transmission to the research personnel to identify and trigger early treatment of CF pulmonary exacerbation. Participants will be enrolled in the study for 12 months. The primary endpoint is change in FEV1 (L) from baseline to 12 months determined by a linear mixed effects model incorporating all quarterly FEV1 measurements. Secondary endpoints include time to first acute protocol-defined pulmonary exacerbation, number of acute pulmonary exacerbations, number of hospitalization days for acute pulmonary exacerbation, time from the end of acute pulmonary exacerbation to onset of subsequent pulmonary exacerbation, change in health related quality of life, change in treatment burden, change in CF respiratory symptoms, and adherence to the study protocol. This study is a first step in establishing alternative approaches to the care of CF pulmonary exacerbations. We hypothesize that early treatment of pulmonary exacerbations has the potential to slow lung function decline, reduce respiratory symptoms and improve the quality of life for individuals with CF. © 2013.

Transient Receptor Potential Ankyrin 1 Channels Modulate Inflammatory Response in Respiratory Cells from Patients with Cystic Fibrosis.

PubMed

Prandini, Paola; De Logu, Francesco; Fusi, Camilla; Provezza, Lisa; Nassini, Romina; Montagner, Giulia; Materazzi, Serena; Munari, Silvia; Gilioli, Eliana; Bezzerri, Valentino; Finotti, Alessia; Lampronti, Ilaria; Tamanini, Anna; Dechecchi, Maria Cristina; Lippi, Giuseppe; Ribeiro, Carla M; Rimessi, Alessandro; Pinton, Paolo; Gambari, Roberto; Geppetti, Pierangelo; Cabrini, Giulio

2016-11-01

Pseudomonas aeruginosa colonization, prominent inflammation with massive expression of the neutrophil chemokine IL-8, and luminal infiltrates of neutrophils are hallmarks of chronic lung disease in patients with cystic fibrosis (CF). The nociceptive transient receptor potential ankyrin (TRPA) 1 calcium channels have been recently found to be involved in nonneurogenic inflammation. Here, we investigate the role of TRPA1 in CF respiratory inflammatory models in vitro. Expression of TRPA1 was evaluated in CF lung tissue sections and cells by immunohistochemistry and immunofluorescence. Epithelial cell lines (A549, IB3-1, CuFi-1, CFBE41o - ) and primary cells from patients with CF were used to: (1) check TRPA1 function modulation, by Fura-2 calcium imaging; (2) down-modulate TRPA1 function and expression, by pharmacological inhibitors (HC-030031 and A-967079) and small interfering RNA silencing; and (3) assess the effect of TRPA1 down-modulation on expression and release of cytokines upon exposure to proinflammatory challenges, by quantitative RT-PCR and 27-protein Bioplex assay. TRPA1 channels are expressed in the CF pseudostratified columnar epithelium facing the bronchial lumina exposed to bacteria, where IL-8 is coexpressed. Inhibition of TRPA1 expression results in a relevant reduction of release of several cytokines, including IL-8 and the proinflammatory cytokines IL-1β and TNF-α, in CF primary bronchial epithelial cells exposed to P. aeruginosa and to the supernatant of mucopurulent material derived from the chronically infected airways of patients with CF. In conclusion, TRPA1 channels are involved in regulating the extent of airway inflammation driven by CF bronchial epithelial cells.

PHOTON SPECTRA IN NPL STANDARD RADIONUCLIDE NEUTRON FIELDS.

PubMed

Roberts, N J

2017-09-23

A HPGe detector has been used to measure the photon spectra from the majority of radionuclide neutron sources in use at NPL (252Cf, 241Am-Be, 241Am-Li, 241Am-B). The HPGe was characterised then modelled to produce a response matrix. The measured pulse height spectra were then unfolded to produce photon fluence spectra. Changes in the photon spectrum with time from a 252Cf source are evident. Spectra from a 2-year-old and 42-year-old 252Cf source are presented showing the change from a continuum to peaks from long-lived isotopes of Cf. Other radionuclide neutron source spectra are also presented and discussed. The new spectra were used to improve the photon to neutron dose equivalent ratios from some earlier work at NPL with GM tubes and EPDs. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparison of conventional filtering and independent component analysis for artifact reduction in simultaneous gastric EMG and magnetogastrography from porcines.

PubMed

Irimia, Andrei; Richards, William O; Bradshaw, L Alan

2009-11-01

In this study, we perform a comparative study of independent component analysis (ICA) and conventional filtering (CF) for the purpose of artifact reduction from simultaneous gastric EMG and magnetogastrography (MGG). EMG/MGG data were acquired from ten anesthetized pigs by obtaining simultaneous recordings using serosal electrodes (EMG) as well as with a superconducting quantum interference device biomagnetometer (MGG). The analysis of MGG waveforms using ICA and CF indicates that ICA is superior to the CF method in its ability to extract respiration and cardiac artifacts from MGG recordings. A signal frequency analysis of ICA- and CF-processed data was also undertaken using waterfall plots, and it was determined that the two methods produce qualitatively comparable results. Through the use of simultaneous EMG/MGG, we were able to demonstrate the accuracy and trustworthiness of our results by comparison and cross-validation within the framework of a porcine model.

Rotational Spectra of Halogenated Ethers Used as Volatile Anaesthetics

NASA Astrophysics Data System (ADS)

Vega-Toribio, Alicia; Lesarri, Alberto; Suenram, Richard D.; Grabow, Jens-Uwe

2009-06-01

Following previous microwave investigations by Suenram et al., we will report on the rotational spectrum of several halogenated ethers used as volatile anaesthetics, including sevoflurane ((CF_3)_2CH-O-CH_2F), isoflurane (CF_3CHCl-O-CHF_2), enflurane (CHFClCF_2-O-CHF_2) and methoxyflurane (CHCl_2CF_2-O-CH_3). This study has been conducted in the 6-18 GHz centimetre-wave region using Balle-Flygare-type FT-microwave spectroscopy. The results will include the analysis of the rotational spectra of minor species in natural abundance (^{13}C and ^{18}O in some cases), structural calculations and auxiliary ab initio modelling. The conformational and structural conclusions will be compared with previous gas-phase electron diffraction and solid-state X-ray diffraction analysis. R. D. Suenram, D. J. Brugh, F. J. Lovas and C. Chu, 51st OSU Int. Symp. On Mol. Spectrosc., Columbus, OH, 1999, RB07

Best practices in the treatment of early cystic fibrosis lung disease.

PubMed

Proesmans, Marijke

2017-02-01

For many years, management of cystic fibrosis (CF) lung disease was focused on symptomatic treatment of chronic lung infection, which is characterized by cough and sputum production, leading to progressive lung damage. With increasing survival and better knowledge of the pathogenesis of CF lung disease, it has become clear that treatment has to start very early because lung damage occurs in young patients, often before obvious symptoms appear. The arrival of new cystic fibrosis transmembrane conductance-regulator (CFTR)-correcting therapies will bring more opportunities to prevent the disease, apart from only treating chronic lung infection. In this review, a summary of the current knowledge of early CF lung disease is provided, based on animal model studies, as well as on data obtained from well structured follow-up programs after newborn screening (NBS). The most important clinical guidelines for treating young CF patients are also summarized.

[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, the Poldi stem survival curve showed better results. Matt surface finish of the stem. However, the link between the CF 30 stem and cement was so strong that, in all 16 revised hips, the stem was removed together with nearly a complete cement mantle. The authors therefore dismiss this as a cause. Also, in the remaining cases of CF 30 aseptic loosening, which had not been revised, radiographic evidence suggested loosening between bone and cement. The authors did not find any movement of the CF stem in its cement mantle. The stem always fitted in with the cement mantle. Erroneous surgical technique or cementing was unlikely. The procedures were performed by experienced orthopedic surgeons who used the second-generation cementing technique. In patients with a Poldi stem, the first-generation cementing method was used and the proportion of aseptic loosening at 6 years of follow-up was only 4 %. In contrast, loosening in patients with the CF 30 stem was 20 % at 6 years and 6 months postoperatively. Shape of the CF 30 stem with the intention to find a relationship between stem shape and its early aseptic loosening, the authors started cooperation with the Institute of Solid Mechanics, Mechatronics and Biomechanics at the Faculty of Mechanical Engineering, Brno University of Technology. Using the method of finite elements, they carried out the stressstrain analysis in a model system. Stress at the cement-bone interface in the CF 30 stem was higher than in the Poldi stem, and this difference was statistically significant. The authors believe that the more frequent loosening found in patients with the CF 30 stem can be accounted for by its shape. The survival curve for the CF 30 femoral stem did not show good results, and therefore this stem is not recommended for implantation. The authors suggest that a more frequent early aseptic loosening of CF 30 stems may have been caused by its unsuitable shape.

Luminosity and redshift dependence of the covering factor of active galactic nuclei viewed with WISE and Sloan digital sky survey

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

Toba, Y.; Matsuhara, H.; Oyabu, S.

2014-06-10

In this work, we investigate the dependence of the covering factor (CF) of active galactic nuclei (AGNs) on the mid-infrared (MIR) luminosity and the redshift. We constructed 12 and 22 μm luminosity functions (LFs) at 0.006 ≤z ≤ 0.3 using Wide-field Infrared Survey Explorer (WISE) data. Combining the WISE catalog with Sloan Digital Sky Survey (SDSS) spectroscopic data, we selected 223,982 galaxies at 12 μm and 25,721 galaxies at 22 μm for spectroscopic classification. We then identified 16,355 AGNs at 12 μm and 4683 AGNs at 22 μm by their optical emission lines and cataloged classifications in the SDSS. Followingmore » that, we estimated the CF as the fraction of Type 2 AGN in all AGNs whose MIR emissions are dominated by the active nucleus (not their host galaxies) based on their MIR colors. We found that the CF decreased with increasing MIR luminosity, regardless of the choice of Type 2 AGN classification criteria, and the CF did not change significantly with redshift for z ≤ 0.2. Furthermore, we carried out various tests to determine the influence of selection bias and confirmed that similar dependences exist, even when taking these uncertainties into account. The luminosity dependence of the CF can be explained by the receding torus model, but the 'modified' receding torus model gives a slightly better fit, as suggested by Simpson.« less

Provider Attitudes and Practices toward Sexual and Reproductive Health Care for Young Women with Cystic Fibrosis.

PubMed

Kazmerski, Traci M; Borrero, Sonya; Sawicki, Gregory S; Abebe, Kaleab Z; Jones, Kelley A; Tuchman, Lisa K; Weiner, Daniel J; Pilewski, Joseph M; Orenstein, David M; Miller, Elizabeth

2017-10-01

To investigate the attitudes and practices of cystic fibrosis (CF) providers toward sexual and reproductive health (SRH) care in young women with CF. Adult and pediatric US CF providers were sent an online survey exploring their attitudes toward SRH importance, SRH care practices, and barriers/facilitators to SRH care in adolescent and/or young adult women. Descriptive statistics and logistic regression were used to analyze results. Attitudes toward the importance of SRH care in patients with CF and self-report of practice patterns of SRH discussion. Respondents (n = 196) were 57% pediatric (111/196) and 24% adult physicians (48/196) and 19% nurse practitioners (NPs)/physician assistants (PAs) (37/196). Ninety-four percent of respondents believed SRH was important for female patients with CF (184/196). More than 75% believed SRH care should be standardized within the CF care model (147/196) and 41% believed the CF team should have the primary role in SRH discussion and care (80/196). For many CF-specific SRH topics, discrepancies emerged between how important respondents believed these were to address and how often they reported discussing these topics in practice. Significant differences in SRH attitudes and practices were present between adult and pediatric physicians. The most significant barriers to SRH care identified were lack of time (70%, 137/196) and the presence of family in clinic room (54%, 106/196). Potential facilitators included training materials for providers (68%, 133/196) and written (71%, 139/196) or online (76%, 149/196) educational resources for patients. CF providers perceive SRH topics as important to discuss, but identify barriers to routine discussion in current practice. Providers endorsed provider training and patient educational resources as means to improve SRH delivery. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Anti-cancer, pharmacokinetic and biodistribution studies of cremophor el free alternative paclitaxel formulation.

PubMed

Jain, Subheet K; Utreja, Puneet; Tiwary, Ashok K; Mahajan, Mohit; Kumar, Nikhil; Roy, Partha

2014-01-01

The aim of the present investigation is to determine the in vivo potential of previously developed and optimized Cremophor EL free paclitaxel (CF-PTX) formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate. CF-PTX was found to have drug loading of 6 mg/ml similar to Cremophor EL based marketed paclitaxel formulation. In the present study, intracellular uptake, repeated dose 28 days sub-acute toxicity, anti-cancer activity, biodistribution and pharmacokinetic studies were conducted to determine in vivo performance of CF-PTX formulation in comparison to marketed paclitaxel formulation. Intracellular uptake of CF-PTX was studied using A549 cells by fluorescence activated cell sorting assay (FACS) and fluorescence microscopy. In vivo anti-cancer activity of CF-PTX was evaluated using Ehrlich ascites carcinoma (EAC) model in mice followed by biodistribution and pharmacokinetic studies. FACS investigation showed that fluorescence marker acridine orange (AO) solution showed only 19.8±1.1% intracellular uptake where as significantly higher uptake was observed in the case of AO loaded CF-PTX formulation (85.4±2.3%). The percentage reduction in tumor volume for CF-PTX (72.5±2.3%) in EAC bearing mice was found to be significantly (p<0.05) higher than marketed formulation (58.6±2.8%) on 14th day of treatment. Pharmacokinetic and biodistribution studies showed sustained plasma concentration of paclitaxel depicted by higher mean residence time (MRT; 18.2±1.8 h) and elimination half life (12.8±0.6 h) with CF-PTX formulation as compared to marketed formulation which showed 4.4±0.2 h MRT and 3.6±0.4 h half life. The results of the present study demonstrated better in vivo performance of CF-PTX and this formulation appears to be a promising carrier for sustained and targeted delivery of paclitaxel.

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.

Control of pulmonary absorption of water-soluble compounds by various viscous vehicles.

PubMed

Yamamoto, Akira; Yamada, Keigo; Muramatsu, Hideaki; Nishinaka, Asako; Okumura, Shigeki; Okada, Naoki; Fujita, Takuya; Muranishi, Shozo

2004-09-10

Effects of various viscous vehicles on the pulmonary absorption of water-soluble drugs were examined by an in situ pulmonary absorption experiment. Gelatin, polyvinylacohol (PVA), hydroxypropylcellose (HPC), chondroitin sulfate A sodium salt (CS), polyacrylic acid (PAA), methylcellulose #400 (MC400) and hyaluronic acid sodium salt (HA) were used as models of viscous vehicles. 5(6)-Carboxyfluorescein (CF) and fluorescein isothiocayanate-labeled dextran with an average molecular weight of 4000 (FD4) were used as water-soluble drugs. The plasma concentration of CF was controlled and regulated in the presence of these viscous vehicles, especially gelatin (1-5%) and polyvinyl alcohol (PVA) 1%. In the pharmacokinetic analysis, the Cmax values of CF significantly decreased, and its Tmax values increased in the presence of these viscous vehicles compared with the control. The MRT and MAT values of CF with these vehicles were significantly higher than those without these vehicles. Therefore, these findings indicated that the viscous vehicles were effective to regulate the absorption rate of CF. On the other hand, the pulmonary absorption of FD4 was not so much affected even in the presence of gelatin and PVA, although PVA slightly decreased MRT value, and significantly decreased Tmax value. Furthermore, we examined the release rate of CF from the cellulose tube containing various concentrations of gelatin. The release rate of CF from the cellulose tube with gelatin was inversely related to the viscosity of gelatin. In addition, the release rate of CF was inversely related to DeltaMAT (DeltaMAT = MATgel(MAT with gelatin)-MATsol(MAT without gelatin)) in the presence of varying concentrations of gelatin. These findings indicated that these viscous vehicles were effective to control the pulmonary absorption of CF, a water-soluble drug with low molecular weight and they might be useful to increase the local concentration of drugs in the lung.

A cross-sectional pilot study of compassion fatigue, burnout, and compassion satisfaction in pediatric palliative care providers in the United States.

PubMed

Kase, Samuel M; Waldman, Elisha D; Weintraub, Andrea S

2018-02-05

Compassion fatigue (CF) is secondary traumatic distress experienced by providers from contact with patients' suffering. Burnout (BO) is job-related distress resulting from uncontrollable workplace factors that manifest in career dissatisfaction. Compassion satisfaction (CS) is emotional fulfillment derived from caring for others. The literature on BO in healthcare providers is extensive, whereas CF and CS have not been comprehensively studied. Because of ongoing exposure to patient and family distress, pediatric palliative care (PPC) providers may be at particular risk for CF. We conducted a cross-sectional pilot study of CF, BO, and CS among PPC providers across the United States. The Compassion Fatigue and Satisfaction Self-Test for Helpers and a questionnaire of professional and personal characteristics were distributed electronically and anonymously to PPC physicians and nurses. Logistic and linear regression models for CF, BO, and CS as a function of potential risk factors were constructed. The survey response rate was 39%, primarily consisting of female, Caucasian providers. The prevalence of CF, BO, and CS was 18%, 12%, and 25%, respectively. Distress about a "clinical situation," physical exhaustion, and personal loss were identified as significant determinants of CF. Distress about "coworkers," emotional depletion, social isolation, and "recent involvement in a clinical situation in which life-prolonging activities were not introduced" were significant determinants of BO. Physical exhaustion, personal history of trauma, "recent involvement in a clinical situation in which life-prolonging activities were not introduced," and not discussing distressing issues were significant predictors of lower CS scores. Significance of results CF and BO directly influence the well-being and professional performance of PPC providers. To provide effective compassionate care to patients, PPC providers must be attentive to predictors of these phenomena. Further work is needed to explore additional causes of CF, BO, and CS in PPC providers as well as potential interventions.

Impact of Orbit Position Errors on Future Satellite Gravity Models

NASA Astrophysics Data System (ADS)

Encarnacao, J.; Ditmar, P.; Klees, R.

2015-12-01

We present the results of a study of the impact of orbit positioning noise (OPN) caused by incomplete knowledge of the Earth's gravity field on gravity models estimated from satellite gravity data. The OPN is simulated as the difference between two sets of orbits integrated on the basis of different static gravity field models. The OPN is propagated into ll-SST data, here computed as averaged inter-satellite accelerations projected onto the Line of Sight (LoS) vector between the two satellites. We consider the cartwheel formation (CF), pendulum formation (PF), and trailing formation (TF) as they produce a different dominant orientation of the LoS vector. Given the polar orbits of the formations, the LoS vector is mainly aligned with the North-South direction in the TF, with the East-West direction in the PF (i.e. no along-track offset), and contains a radial component in the CF. An analytical analysis predicts that the CF suffers from a very high sensitivity to the OPN. This is a fundamental characteristic of this formation, which results from the amplification of this noise by diagonal components of the gravity gradient tensor (defined in the local frame) during the propagation into satellite gravity data. In contrast, the OPN in the data from PF and TF is only scaled by off-diagonal gravity gradient components, which are much smaller than the diagonal tensor components. A numerical analysis shows that the effect of the OPN is similar in the data collected by the TF and the PF. The amplification of the OPN errors for the CF leads to errors in the gravity model that are three orders of magnitude larger than those in case of the PF. This means that any implementation of the CF will most likely produce data with relatively low quality since this error dominates the error budget, especially at low frequencies. This is particularly critical for future gravimetric missions that will be equipped with highly accurate ranging sensors.

Studies of the kinetics and mechanisms of perfluoroether reactions on iron and oxidized iron surfaces

NASA Technical Reports Server (NTRS)

Napier, Mary E.; Stair, Peter C.

1992-01-01

Polymeric perfluoroalkylethers are being considered for use as lubricants in high temperature applications, but have been observed to catalytically decompose in the presence of metals. X-ray photoelectron spectroscopy (XPS) and temperature programmed desorption (TPD) were used to explore the decomposition of three model fluorinated ethers on clean polycrystalline iron surfaces and iron surfaces chemically modified with oxygen. Low temperature adsorption of the model fluorinated ethers on the clean, oxygen modified and oxidized iron surfaces was molecular. Thermally activated defluorination of the three model compounds was observed on the clean iron surface at remarkably low temperatures, 155 K and below, with formation of iron fluoride. Preferential C-F bond scission occurred at the terminal fluoromethoxy, CF3O, of perfluoro-1-methoxy-2-ethoxy ethane and perfluoro-1-methoxy-2-ethoxy propane and at CF3/CF2O of perfluoro-1,3-diethoxy propane. The reactivity of the clean iron toward perfluoroalkylether decomposition when compared to other metals is due to the strength of the iron fluoride bond and the strong electron donating ability of the metallic iron. Chemisorption of an oxygen overlayer lowered the reactivity of the iron surface to the adsorption and decomposition of the three model fluorinated ethers by blocking active sites on the metal surface. Incomplete coverage of the iron surface with chemisorbed oxygen results in a reaction which resembles the defluorination reaction observed on the clean iron surface. Perfluoro-1-methoxy-2-ethoxy ethane reacts on the oxidized iron surface at 138 K, through a Lewis acid assisted cleavage of the carbon oxygen bond, with preferential attack at the terminal fluoromethoxy, CF3O. The oxidized iron surface did not passivate, but became more reactive with time. Perfluoro-1-methoxy-2-ethoxy propane and perfluoro-1,3-diethoxy propane desorbed prior to the observation of decomposition on the oxidized iron surface.

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.

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 are 2sigma). The reactions are reported to proceed through the abstraction of an H atom to form HCl and the corresponding halo-alkyl radical. At 298 K and 1 Torr, yields on HCl of 0.95 +/- 0.38 and 0.97 +/- 0.16 (errors are 2sigma) were obtained for CF(3)CF(2)CF(2)OCH(3) and CF(3)CF(2)CF(2)CH(2)OH, respectively. The obtained kinetic rate constants are related to the previous data in the literature, showing a good agreement taking into account the error limits. Comparing the obtained results at room temperature, k (1) and k (2), HFE-7000 is significantly less reactive than its isomer C(3)F(7)CH(2)OH. A similar behavior has been reported for the reactions of other fluorinated alcohols and their isomeric fluorinated ethers with Cl atoms. Literature data, together with the results reported in this work, show that, for both fluorinated ethers and alcohols, the kinetic rate constant may be considered as not dependent on the number of -CF(2)- in the perfluorinated chain. This result may be useful since it is possible to obtain the required physicochemical properties for a given application by changing the number of -CF(2)- without changes in the atmospheric reactivity. Furthermore, lifetimes estimations for these CFCs substitutes are calculated and discussed. The average estimated Cl lifetimes are 256 and 38 years for HFE-7000 and C(3)H(7)CH(2)OH, respectively. The studied CFCs' substitutes are relatively short-lived and OH reaction constitutes their main reactive sink. The average contribution of Cl reactions to global lifetime is about 2% in both cases. Nevertheless, under local conditions as in the marine boundary layer, tau (Cl) values as low as 2.5 and 0.4 years for HFE-7000 and C(3)H(7)CH(2)OH, respectively, are expected, showing that the contribution of Cl to the atmospheric degradation of these CFCs substitutes under such conditions may constitute a relevant sink. In the case of CF(3)CF(2)CF(2)OCH(3), significant activation energy has been measured, thus the use of kinetic rate coefficient only at room temperature would result in underestimations of lifetimes and GWPs. The results obtained in this work may be helpful within the database used in the modeling studies of coastal areas. The knowledge of the atmospheric behavior and the structure-reactivity relationship discussed in this work may also contribute to the development of new environmentally acceptable chemicals. New volatile materials susceptible of emission to the troposphere should be subject to the study of their reactions with OH and Cl in the range of temperature of the troposphere. The knowledge of the temperature dependence of the kinetic rate constants, as it is now reported for the case of reactions 1 and 2, will allow more accurate lifetimes and related magnitudes like GWPs. Nevertheless, a better knowledge of the vertical Cl tropospheric distribution is still required.

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.

Targeting to cells of fluorescent liposomes covalently coupled with monoclonal antibody or protein A

NASA Astrophysics Data System (ADS)

Leserman, Lee D.; Barbet, Jacques; Kourilsky, François; Weinstein, John N.

1980-12-01

Many applications envisioned for liposomes in cell biology and chemotherapy require their direction to specific cellular targets1-3. The ability to use antibody as a means of conferring specificity to liposomes would markedly increase their usefulness. We report here a method for covalently coupling soluble proteins, including monoclonal antibody and Staphylococcus aureus protein A (ref. 4), to small sonicated liposomes, by using the heterobifunctional cross-linking reagent N-hydroxysuccinimidyl 3-(2-pyridyldithio)propionate (SPDP, Pharmacia). Liposomes bearing covalently coupled mouse monoclonal antibody against human β2-microglobulin [antibody B1.1G6 (IgG2a, κ) (B. Malissen et al., in preparation)] bound specifically to human, but not to mouse cells. Liposomes bearing protein A became bound to human cells previously incubated with the B1.1G6 antibody, but not to cells incubated without antibody. The coupling method results in efficient binding of protein to the liposomes without aggregation and without denaturation of the coupled ligand; at least 60% of liposomes bound functional protein. Further, liposomes did not leak encapsulated carboxyfluorescein (CF) as a consequence of the reaction.

Carbon footprint and land requirement for dairy herd rations: impacts of feed production practices and regional climate variations.

PubMed

Henriksson, M; Cederberg, C; Swensson, C

2014-08-01

Feed production is a significant source of greenhouse gas (GHG) emissions from dairy production and demands large arable and pasture acreage. This study analysed how regional conditions influence GHG emissions of dairy feed rations in a life cycle perspective, that is the carbon footprint (CF) and the land area required. Factors assessed included regional climate variations, grass/clover silage nutrient quality, feedstuff availability, crop yield and feed losses. Using the Nordic feed evaluation model NorFor, rations were optimised for different phases of lactation, dry and growing periods for older cows, first calvers and heifers by regional feed advisors and combined to annual herd rations. Feed production data at farm level were based on national statistics and studies. CF estimates followed standards for life cycle assessment and used emissions factors provided by IPCC. The functional unit was 'feed consumption to produce 1 kg energy corrected milk (ECM) from a cow with annual milk yield of 9 900 kg ECM including replacement animals and feed losses'. Feed ration CF varied from 417 to 531 g CO2 e/kg ECM. Grass/clover silage contributed more than 50% of total GHG emissions. Use of higher quality silage increased ration CF by up to 5% as a result of an additional cut and increased rates of synthetic N-fertiliser. Domestically produced horse bean (Vicia faba), by-products from the sugar industry and maize silage were included in the rations with the lowest CF, but horse bean significantly increased ration land requirement. Rations required between 1.4 to 2 m2 cropland and 0.1 to 0.2 m2/kg semi-natural grassland per kg ECM and year. Higher yield levels reduced ration total CF. Inclusion of GHG emissions from land use change associated with Brazilian soya feed significantly increased ration CF. Ration CF and land use depended on ration composition, which was highly influenced by the regional availability and production of feedstuffs. The impact of individual feedstuffs on ration CF varies due to, for example, cultivation practices and climate conditions and feedstuffs should therefore be assessed in a ration and regional perspective before being used to decrease milk CF. Land use efficiency should be considered together with ration CF, as these can generate goal conflicts.

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

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.

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.

Effects of long term treatment with high doses of odanacatib on bone mass, bone strength, and remodeling/modeling in newly ovariectomized monkeys.

PubMed

Duong, L T; Pickarski, M; Cusick, T; Chen, C M; Zhuo, Y; Scott, K; Samadfam, R; Smith, S Y; Pennypacker, B L

2016-07-01

The objectives here were to evaluate the effects of odanacatib (ODN) at doses exceeding the clinical exposure on biomechanical properties of lumbar vertebrae (LV), hip and central femur (CF), and compare ODN to alendronate (ALN) on bone remodeling/modeling in ovariectomized (OVX) monkeys. Ten days post-surgery, animals were treated with vehicle (VEH), ODN-L (2mg/kg/day, p.o.), ODN-H (8/4mg/kg/day), or ALN (30μg/kg/week, s.c.) for 20months. An intact group was also included. ODN-L provided systemic exposures of 1.8-fold of clinical exposure. ODN-H started at 20-fold for 5.5months, and then reduced to 7.8-fold of clinical exposure, compared to ALN at approximated clinical exposure. From cross sectional analyses, LV density and peak load in ODN at both doses or ALN were not different from VEH or Intact. However, cortical thickness of femoral neck (FN) and CF in ODN were higher (21-34%, p<0.05) than VEH, due to smaller endocortical (Ec) perimeter of FN (10-11%; p<0.05) and CF (9-12%; ODN-L, p<0.05), and larger CF periosteal (Ps) perimeter (2-12%; ODN-H, p<0.001) versus VEH. ODN groups also showed slightly higher cortical porosity and Ps non-lamellar bone in CF. ODN-H treatment resulted in higher CF peak load (p<0.05) versus VEH. For all bone sites analyzed, a positive, linear relationship (r(2)=0.46-0.69, p<0.0001) of peak load to density or structural parameters was demonstrated. No treatment-related differences in the derived intrinsic strength properties were evidenced as compared between groups. ALN reduced all remodeling surfaces without affecting Ps modeling. Trabecular and intracortical remodeling were reduced in ODN groups, similar to ALN. Ec mineralizing surface in ODN-H trended to be lower than VEH by month 20, but Ec bone formation indices in ODN groups generally were not different from VEH. Ps modeling in ODN groups was significantly higher than other treatment groups. This study overall demonstrated the bone safety profile of ODN and its unique mechanism on cortical bone supporting the clinical application for osteoporosis treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Choosing Models for Health Care Cost Analyses: Issues of Nonlinearity and Endogeneity

PubMed Central

Garrido, Melissa M; Deb, Partha; Burgess, James F; Penrod, Joan D

2012-01-01

Objective To compare methods of analyzing endogenous treatment effect models for nonlinear outcomes and illustrate the impact of model specification on estimates of treatment effects such as health care costs. Data Sources Secondary data on cost and utilization for inpatients hospitalized in five Veterans Affairs acute care facilities in 2005–2006. Study Design We compare results from analyses with full information maximum simulated likelihood (FIMSL); control function (CF) approaches employing different types and functional forms for the residuals, including the special case of two-stage residual inclusion; and two-stage least squares (2SLS). As an example, we examine the effect of an inpatient palliative care (PC) consultation on direct costs of care per day. Data Collection/Extraction Methods We analyzed data for 3,389 inpatients with one or more life-limiting diseases. Principal Findings The distribution of average treatment effects on the treated and local average treatment effects of a PC consultation depended on model specification. CF and FIMSL estimates were more similar to each other than to 2SLS estimates. CF estimates were sensitive to choice and functional form of residual. Conclusions When modeling cost or other nonlinear data with endogeneity, one should be aware of the impact of model specification and treatment effect choice on results. PMID:22524165

Up-to-date and projected estimates of survival for people with cystic fibrosis using baseline characteristics: A longitudinal study using UK patient registry data.

PubMed

Keogh, Ruth H; Szczesniak, Rhonda; Taylor-Robinson, David; Bilton, Diana

2018-03-01

Cystic fibrosis (CF) is the most common inherited disease in Caucasians, affecting around 10,000 individuals in the UK today. Prognosis has improved considerably over recent decades with ongoing improvements in treatment and care. Providing up-to-date survival predictions is important for patients, clinicians and health services planning. Flexible parametric survival modelling of UK CF Registry data from 2011 to 2015, capturing 602 deaths in 10,428 individuals. Survival curves were estimated from birth; conditional on reaching older ages; and projected under different assumptions concerning future mortality trends, using baseline characteristics of sex, CFTR genotype (zero, one, two copies of F508del) and age at diagnosis. Male sex was associated with better survival, as was older age at diagnosis, but only in F508del non-homozygotes. Survival did not differ by genotype among individuals diagnosed at birth. Median survival ages at birth in F508del homozygotes were 46years (males) and 41years (females), and similar in non-homozygotes diagnosed at birth. F508del heterozygotes diagnosed aged 5 had median survival ages of 57 (males) and 51 (females). Conditional on survival to 30, median survival age rises to 52 (males) and 49 (females) in homozygotes. Mortality rates decreased annually by 2% during 2006-2015. Future improvements at this rate suggest median survival ages for F508del homozygous babies of 65 (males) and 56 (females). Over half of babies born today, and of individuals aged 30 and above today, can expect to survive into at least their fifth decade. Evidence before this study We searched PubMed with terms "(cystic fibrosis survival) and (projection OR model OR registry OR United Kingdom OR UK)" to identify relevant studies on survival estimates for individuals with cystic fibrosis (CF). We also considered the most recent annual report from the UK Cystic Fibrosis Registry (Cystic Fibrosis Trust, 2016), a review by Buzzetti and colleagues (2009), the chapter on Epidemiology of Cystic Fibrosis by MacNeill (2016), the study of MacKenzie and colleagues (2014), and references therein. There have been many studies of factors associated with survival in CF; most have focused on identifying risk factors, and only a few have presented estimated survival curves, which are the focus of this work. The most recent study of survival in the UK is by Dodge and colleagues (2007), who used data obtained from CF clinics and the national death register, and gave an estimate of survival for babies born in 2003. We found no previous studies that have obtained detailed information on survival using UK Cystic Fibrosis Registry data. Jackson and colleagues obtained survival estimates for the US and Ireland using registry data (Jackson et al., 2011). MacKenzie and colleagues used US Cystic Fibrosis Foundation Patient Registry data from 2000 to 2010 to project survival for children born and diagnosed with CF in 2010, accounting for sex, genotype and age at diagnosis (MacKenzie et al., 2014). Previous studies on estimated survival in CF have become out of date or have not accounted for the full range of patient characteristics available at birth. Few have presented conditional survival estimates (Dodge et al., 2007). Added value of this study This is the first study to yield detailed survival statistics using the UK Cystic Fibrosis Registry, which is one of the largest national CF registries outside of the US and has almost complete coverage of the UK CF population. The primary goal was to leverage the long-term follow-up of the nearly complete UK CF population available in the Registry for the purposes of producing accurate, precise predictions in the modern era of CF care. Estimates are presented from birth and conditional on survival to older ages. These are the first conditional estimates in CF to also account for genotype, sex and age at diagnosis, which were each included in the modelling using a flexible approach. Projections are also provided under different scenarios based on downward trends in mortality rates. Our use of flexible parametric survival models is novel in this field, and our approach could be used to provide modern survival statistics for other chronic diseases and disorders. Implications of all the available evidence Our estimates of future survival in CF under a range of different scenarios are based on data on nearly all individuals living with the disease in the UK in recent times, reflective of a modern era of care, and are most appropriate for the families of babies being born in the present day with CF. Conditional estimates inform patients who have already reached an older age, and their clinicians. Over half of babies born today, and of individuals aged 30years and above alive today, can expect to survive into their fifth decade. Insights based on our survival projections can be used to inform future needs in CF health care provision. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype

PubMed Central

Kharbanda, Sandhya; Koh, Winston; Martin, Lance R.; Khush, Kiran K.; Valantine, Hannah; Pritchard, Jonathan K.; De Vlaminck, Iwijn

2017-01-01

Quantification of cell-free DNA (cfDNA) in circulating blood derived from a transplanted organ is a powerful approach to monitoring post-transplant injury. Genome transplant dynamics (GTD) quantifies donor-derived cfDNA (dd-cfDNA) by taking advantage of single-nucleotide polymorphisms (SNPs) distributed across the genome to discriminate donor and recipient DNA molecules. In its current implementation, GTD requires genotyping of both the transplant recipient and donor. However, in practice, donor genotype information is often unavailable. Here, we address this issue by developing an algorithm that estimates dd-cfDNA levels in the absence of a donor genotype. Our algorithm predicts heart and lung allograft rejection with an accuracy that is similar to conventional GTD. We furthermore refined the algorithm to handle closely related recipients and donors, a scenario that is common in bone marrow and kidney transplantation. We show that it is possible to estimate dd-cfDNA in bone marrow transplant patients that are unrelated or that are siblings of the donors, using a hidden Markov model (HMM) of identity-by-descent (IBD) states along the genome. Last, we demonstrate that comparing dd-cfDNA to the proportion of donor DNA in white blood cells can differentiate between relapse and the onset of graft-versus-host disease (GVHD). These methods alleviate some of the barriers to the implementation of GTD, which will further widen its clinical application. PMID:28771616

Enhanced electro-Fenton Mineralization of Acid Orange 7 Using a Carbon Nanotube Fiber Based Cathode

NASA Astrophysics Data System (ADS)

Huong Le, Thi Xuan; Alemán, Belén; Vilatela, Juan J.; Bechelany, Mikhael; Cretin, Marc

2018-02-01

A new cathodic material for electro-Fenton (EF) process was prepared based on a macroscopic fiber (CNTF) made of mm long carbon nanotubes directly spun from the gas phase by floating catalyst CVD, on a carbon fiber (CF) substrate. CNTF@CF electrode is a highly graphitic material combining a high surface area ( 260 m2/g) with high electrical conductivity and electrochemical stability . One kind of azo dye, acid orange 7 (AO7), was used as model bio-refractory pollutant to be treated at CNTF@CF cathode in acidic aqueous medium (pH 3.0). The experimental results pointed out that AO7 and its organic intermediate compounds were totally mineralized by hydroxyl radical generated from Fenton reaction. In fact, 96.7 % of the initial TOC was eliminated in 8h of electrolysis by applying a current of -25 mA and ferrous ions as catalyst at concentration of 0.2 mM. At the same electrolysis time, only 23.7 % of TOC removal found on CF support which proved the high mineralization efficiency of new material thanks to CNTs deposition. The CNTF@CF cathode maintained stable its activity during five experimental cycles of EF set-up. The results indicated that CNTF@CF material could be a potential choice for wastewater treatment containing bio-refractory by electrochemical advanced oxidation processes (EAOPs).

{sup 1}H and {sup 19}F spin-lattice relaxation and CH{sub 3} or CF{sub 3} reorientation in molecular solids containing both H and F atoms

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

Beckmann, Peter A., E-mail: pbeckman@brynmawr.edu; Rheingold, Arnold L.

2016-04-21

The dynamics of methyl (CH{sub 3}) and fluoromethyl (CF{sub 3}) groups in organic molecular (van der Waals) solids can be exploited to survey their local environments. We report solid state {sup 1}H and {sup 19}F spin-lattice relaxation experiments in polycrystalline 3-trifluoromethoxycinnamic acid, along with an X-ray diffraction determination of the molecular and crystal structure, to investigate the intramolecular and intermolecular interactions that determine the properties that characterize the CF{sub 3} reorientation. The molecule is of no particular interest; it simply provides a motionless backbone (on the nuclear magnetic resonance (NMR) time scale) to investigate CF{sub 3} reorientation occurring on themore » NMR time scale. The effects of {sup 19}F–{sup 19}F and {sup 19}F–{sup 1}H spin-spin dipolar interactions on the complicated nonexponential NMR relaxation provide independent inputs into determining a model for CF{sub 3} reorientation. As such, these experiments provide much more information than when only one spin species (usually {sup 1}H) is present. In Sec. IV, which can be read immediately after the Introduction without reading the rest of the paper, we compare the barrier to CH{sub 3} and CF{sub 3} reorientation in seven organic solids and separate this barrier into intramolecular and intermolecular components.« less

STELLAR CONTRIBUTION FUNCTIONS IN THE AGE OF CHEMICAL STRATIFICATION

NASA Astrophysics Data System (ADS)

Cowley, Charles; Sheminova, Valya; Castelli, Fiorella; Monier, Richard

2018-01-01

Contribution functions (CF's) were important tools to probe formation depths of features in the early numerical calculations of analytical stellar spectroscopy. In more recent work, CF's have played a minor role. Gray's (2005) text briefly discusses CF's, but CF's are not in Hubeny and Mihalas (2015). Gurtovenko and Sheminova (2015) give an extensive review of contribution functions in a recent preprint (arXiv:1505.00975). The realization that the atmospheres of certain stars are chemically stratified (Ryabchikova, Wade \\& LeBlanc, 2003, in IAU Symp. 210), and much subsequent work makes CF's of current interest. We employ new as well as older methods to compute CF's to find important layers, either for specific intensity or line depth for various points on the line profile. The most important layer is the one that causes the biggest change in the magnitude of the feature when the line absorption coefficient is set equal to zero for successive layers. This is readily done for a stratified or unstratified model. For an equivalent width, W, we calculate $(W-W_i/W) $, where $W_i$ is the equivalent width without absorption from the $i^th$ layer. We concentrate on cases where stratification is most obvious, for example, the Ca II K-line profile in the roAp stars and HR 6000 (Castelli, et al. 2017, A\\&A, 601, A119).

Durability of carbon fiber reinforced shape memory polymer composites in space

NASA Astrophysics Data System (ADS)

Jang, Joon Hyeok; Hong, Seok Bin; Ahn, Yong San; Kim, Jin-Gyun; Nam, Yong-Youn; Lee, Geun Ho; Yu, Woong-Ryeol

2016-04-01

Shape memory polymer (SMP) is one of smart polymers which exhibit shape memory effect upon external stimuli. Recently, shape memory polymer composites (SMPCs) have been considered for space structure instead of shape memory alloys due to their deformability, lightweight and large recovery ratio, requiring characterization of their mechanical properties against harsh space environment and further prediction of the durability of SMPCs in space. As such, the durability of carbon fiber reinforced shape memory polymer composites (CF-SMPCs) was investigated using accelerated testing method based on short-term testing of CF-SMPCs in harsh condition. CF-SMPCs were prepared using woven carbon fabrics and a thermoset SMP via vacuum assisted resin transfer molding process. Bending tests with constant strain rate of CF-SMPCs were conducted using universal tensile machine (UTM) and Storage modulus test were conducted using dynamic mechanical thermal analysis (DMTA). Using the results, a master curve based on time-temperature superposition principle was then constructed, through which the mechanical properties of CF-SMPCs at harsh temperature were predicted. CF-SMPCs would be exposed to simulated space environments under ultra-violet radiations at various temperatures. The mechanical properties including flexural and tensile strength and shape memory properties of SMPCs would be measured using UTM before and after such exposures for comparison. Finally, the durability of SMPCs in space would be assessed by developing a degradation model of SMPC.

Magnetic Excitations in Polyoxotungstate-Supported Lanthanoid Single-Molecule Magnets: An Inelastic Neutron Scattering and ab Initio Study.

PubMed

Vonci, Michele; Giansiracusa, Marcus J; Van den Heuvel, Willem; Gable, Robert W; Moubaraki, Boujemaa; Murray, Keith S; Yu, Dehong; Mole, Richard A; Soncini, Alessandro; Boskovic, Colette

2017-01-03

Inelastic neutron scattering (INS) has been used to investigate the crystal field (CF) magnetic excitations of the analogs of the most representative lanthanoid-polyoxometalate single-molecule magnet family: Na 9 [Ln(W 5 O 18 ) 2 ] (Ln = Nd, Tb, Ho, Er). Ab initio complete active space self-consistent field/restricted active space state interaction calculations, extended also to the Dy analog, show good agreement with the experimentally determined low-lying CF levels, with accuracy better in most cases than that reported for approaches based only on simultaneous fitting to CF models of magnetic or spectroscopic data for isostructural Ln families. In this work we demonstrate the power of a combined spectroscopic and computational approach. Inelastic neutron scattering has provided direct access to CF levels, which together with the magnetometry data, were employed to benchmark the ab initio results. The ab initio determined wave functions corresponding to the CF levels were in turn employed to assign the INS transitions allowed by selection rules and interpret the observed relative intensities of the INS peaks. Ultimately, we have been able to establish the relationship between the wave function composition of the CF split Ln III ground multiplets and the experimentally measured magnetic and spectroscopic properties for the various analogs of the Na 9 [Ln(W 5 O 18 ) 2 ] family.

Effect of COPD treatments on MRP1-mediated transport in bronchial epithelial cells

PubMed Central

van der Deen, Margaretha; Homan, Sandra; Timmer-Bosscha, Hetty; Scheper, Rik J; Timens, Wim; Postma, Dirkje S; de Vries, Elisabeth G

2008-01-01

Background Smoking is the principle risk factor for development of chronic obstructive pulmonary disease (COPD). Multidrug resistance-associated protein 1 (MRP1) is known to protect against toxic compounds and oxidative stress, and might play a role in protection against smoke-induced disease progression. We questioned whether MRP1-mediated transport is influenced by pulmonary drugs that are commonly prescribed in COPD. Methods The immortalized human bronchial epithelial cell line 16HBE14o− was used to analyze direct in vitro effects of budesonide, formoterol, ipratropium bromide and N-acetylcysteine (NAC) on MRP1-mediated transport. Carboxyfluorescein (CF) was used as a model MRP1 substrate and was measured with functional flow cytometry. Results Formoterol had a minor effect, whereas budesonide concentration-dependently decreased CF transport by MRP1. Remarkably, addition of formoterol to the highest concentration of budesonide increased CF transport. Ipratropium bromide inhibited CF transport at low concentrations and tended to increase CF transport at higher levels. NAC increased CF transport by MRP1 in a concentration-dependent manner. Conclusions Our data suggest that, besides their positive effects on respiratory symptoms, budesonide, formoterol, ipratropium bromide, and NAC modulate MRP1 activity in bronchial epithelial cells. Further studies are required to assess whether stimulation of MRP1 activity is beneficial for long-term treatment of COPD. PMID:18990976

Primary Neoplasms of Bones in Mice: Retrospective Study and Review of Literature

PubMed Central

Kavirayani, A. M.; Sundberg, J. P.; Foreman, O.

2011-01-01

To compare and summarize the mechanisms, frequencies of occurrence, and classification schemes of spontaneous, experimental, and genetically engineered, mouse skeletal neoplasms, the literature was reviewed and archived case material at The Jackson Laboratory examined. The frequency of occurrence of spontaneous bone neoplasms was less than 1% for most strains, with the exceptions of osteomas in CF-1 (5.5% and 10% in two studies) and OF-1 outbred strains (35%), and osteosarcomas in NOD/ShiLtJ (11.5%) and NOD derived (7.1%) mice. The frequency was 100% for osteochondromas induced by conditional inactivation of exostoses (multiple) 1 (Ext1) in chondrocytes, osteosarcomas induced by tibial intramedullary inoculation of Moloney’s murine sarcoma virus, and osteosarcomas induced by conditional inactivation of Trp53-with or without inactivation of Rb1-in osteoblast precursors. Spontaneous osteogenic neoplasms were more frequent than spontaneous cartilaginous and vascular types. Malignant neoplasms were more frequent than benign ones. The age of occurrence for spontaneous neoplasms ranged from 37 to 720 (Mean 316.35) days for benign, and 35 to 990 (Mean 299.28) days for malignant neoplasms. In genetically engineered mice, the average age of occurrence ranged from 28 to 70 days for benign, and from 35 to 690 days for malignant neoplasms. Histologically, non-osteogenic neoplasms were similar across strains and mutant stocks; osteogenic neoplasms exhibited greater diversity. This comparison and summarization of mouse bone neoplasms provides valuable information for the selection of strains to create, compare, and validate models of bone neoplasms. PMID:21343597

Fluorine-19 magnetic resonance imaging probe for the detection of tau pathology in female rTg4510 mice.

PubMed

Yanagisawa, Daijiro; Ibrahim, Nor Faeizah; Taguchi, Hiroyasu; Morikawa, Shigehiro; Kato, Tomoko; Hirao, Koichi; Shirai, Nobuaki; Sogabe, Takayuki; Tooyama, Ikuo

2018-05-01

Aggregation of tau into neurofibrillary tangles (NFTs) is characteristic of tauopathies, including Alzheimer's disease. Recent advances in tau imaging have attracted much attention because of its potential contributions to early diagnosis and monitoring of disease progress. Fluorine-19 magnetic resonance imaging ( 19 F-MRI) may be extremely useful for tau imaging once a high-quality probe has been formulated. In this investigation, a novel fluorine-19-labeling compound has been developed as a probe for tau imaging using 19 F-MRI. This compound is a buta-1,3-diene derivative with a polyethylene glycol side chain bearing a CF 3 group and is known as Shiga-X35. Female rTg4510 mice (a mouse model of tauopathy) and wild-type mice were intravenously injected with Shiga-X35, and magnetic resonance imaging of each mouse's head was conducted in a 7.0-T horizontal-bore magnetic resonance scanner. The 19 F-MRI in rTg4510 mice showed an intense signal in the forebrain region. Analysis of the signal intensity in the forebrain region revealed a significant accumulation of fluorine-19 magnetic resonance signal in the rTg4510 mice compared with the wild-type mice. Histological analysis showed fluorescent signals of Shiga-X35 binding to the NFTs in the brain sections of rTg4510 mice. Data collected as part of this investigation indicate that 19 F-MRI using Shiga-X35 could be a promising tool to evaluate tau pathology in the brain. © 2017 Wiley Periodicals, Inc.

Atmospheric observations and inverse modelling for quantifying emissions of point-source synthetic greenhouse gases in East Asia

NASA Astrophysics Data System (ADS)

Arnold, Tim; Manning, Alistair; Li, Shanlan; Kim, Jooil; Park, Sunyoung; Muhle, Jens; Weiss, Ray

2017-04-01

The fluorinated species carbon tetrafluoride (CF4; PFC-14), nitrogen trifluoride (NF3) and trifluoromethane (CHF3; HFC-23) are potent greenhouse gases with 100-year global warming potentials of 6,630, 16,100 and 12,400, respectively. Unlike the majority of CFC-replacements that are emitted from fugitive and mobile emission sources, these gases are mostly emitted from large single point sources - semiconductor manufacturing facilities (all three), aluminium smelting plants (CF4) and chlorodifluoromethane (HCFC-22) factories (HFC-23). In this work we show that atmospheric measurements can serve as a basis to calculate emissions of these gases and to highlight emission 'hotspots'. We use measurements from one Advanced Global Atmospheric Gases Experiment (AGAGE) long term monitoring sites at Gosan on Jeju Island in the Republic of Korea. This site measures CF4, NF3 and HFC-23 alongside a suite of greenhouse and stratospheric ozone depleting gases every two hours using automated in situ gas-chromatography mass-spectrometry instrumentation. We couple each measurement to an analysis of air history using the regional atmospheric transport model NAME (Numerical Atmospheric dispersion Modelling Environment) driven by 3D meteorology from the Met Office's Unified Model, and use a Bayesian inverse method (InTEM - Inversion Technique for Emission Modelling) to calculate yearly emission changes over seven years between 2008 and 2015. We show that our 'top-down' emission estimates for NF3 and CF4 are significantly larger than 'bottom-up' estimates in the EDGAR emissions inventory (edgar.jrc.ec.europa.eu). For example we calculate South Korean emissions of CF4 in 2010 to be 0.29±0.04 Gg/yr, which is significantly larger than the Edgar prior emissions of 0.07 Gg/yr. Further, inversions for several separate years indicate that emission hotspots can be found without prior spatial information. At present these gases make a small contribution to global radiative forcing, however, given that the impact of these long-lived gases could rise significantly and that point sources of such gases can be mitigated, atmospheric monitoring could be an important tool for aiding emissions reduction policy.

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.

SU-F-T-430: Validation of IBEAM Evo Couch Top for Different Relative Electron Density (RED) Combination During Photon Beam Dose Calculation in Monaco− Treatment Planning System

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

Manigandan, D; Kumar, M; Mohandas, P

Purpose: Validation of iBEAM™ evo couch-top for different relative electron density (RED) combination during photon beam dose calculation in Monaco− TPS. Methods: The iBEAM™ evo couch-top has two layers:outer carbon fiber (CF) and inner foam core (FC). To study the beam intensity attenuation of couch-top, measured doses were compared with doses calculated for different REDs. Measurements were performed in solid water phantom with PTW-0.125cc ion-chamber positioned at center of the phantom with 5.3cm thickness slabs placed above and below the chamber. Similarly, in TPS, iBEAM™ evo couch-top was simulated and doses were calculated for different RED combinations (0.2CF-0.2FC, 0.4CF-0.2FC, 0.6CF-0.2FC,more » 0.8CF-0.2FC, and 1.0CF-0.2FC) by using Monte Carlo dose calculation algorithm in Monaco TPS (V5.1). Doses were measured for every 10 degree gantry angle separation, 10×10cm{sup 2} field size and 6MV photons. Then, attenuation is defined as the ratio of output at posterior gantry angle to output of its opposed anterior gantry angle (e.g.225°/45°). output fluctuation with different gantry angle was within ±0.21%. To confirm above results, dose-planes were measured for five pelvic VMAT plans (360°arc) in PTW two-dimensional array and compared with different calculated dose-planes of above-mentioned couch REDs. Gamma pass rates<1.00) were analyzed for 3%/2mm criteria. Results: Measured and calculated attenuation was in good agreement for the RED combination of 0.2CF-0.2FC and difference was within ±0.515%. However, other density combination showed difference of ±0.9841%, ±1.667%, ±2.9241% and ±2.8832% for 0.4CF-0.2FC, 0.6CF-0.2FC, 0.8CF-0.2FC, and 1.0CF-0.2FC, respectively. Maximum couch-top attenuation was observed at 110°–120° and 240°–250° and decreases linearly as the gantry angle approaches 180°. Moreover, gamma pass rate confirmed the above results and showed maximum pass rate of 96.23% for 0.2CF-0.2FC, whereas others were 95.72%, 95.12%, 94.31% and 93.24%. Conclusion: RED value of 0.2CF-0.2FC was found to be suitable for accurate couch-top modeling for 6MV photon beam Monte Carlo calculations in Monaco TPS.« less

Venus' center of figure-center of mass offset

NASA Technical Reports Server (NTRS)

Bindschadler, Duane L.; Schubert, Gerald; Ford, Peter G.

1994-01-01

Magellan altimetry data reveal that the center of figure (CF) of Venus is displaced approximately 280 m from its center of mass (CM) toward 4.4 deg S, 135.8 deg E, a location in Aphrodite Terra. This offset is smaller than those of other terrestrial planets but larger than the estimated error, which is no more than a few tens of meters. We examine the possibility that the CF-CM offset is related to specific geologic provinces on Venus by deriving three simple models for the offset: a thick-crust model, a hotspot model, and a thick-lithosphere model. The offset caused by a region of thick crust depends upon the region's extent, the crust-mantle density contrast, and the thickness of excess crust. A hotspot-related offset depends on the extent of the thermally anomalous region and the magnitude of the thermal anomaly. Offset due to a region of thick lithosphere depends upon the extent of the region, the average temperature contrast across the lithosphere, and the amount of excess lithosphere. We apply the three models to Venus plateau-shaped highlands, volcanic rises, and lowlands, respectively, in an attempt to match the observed CF-CM offset location and magnitude. The influence of most volcanic rises and of Ishtar Terra on the CF-CM offset must be quite small if we are to explain the direction of the observed offset. The lack of influence of volcanic rises can be explained if the related thermal anomalies are limited to a few hundred degrees or less and are plume-shaped (i.e., characterized by a flattened sublithospheric `head' with a narrow cylindrical feeder `tail'). The unimportance of Ishtar Terra is most easily explained if it lies atop a significant mantle downwelling.

Heat transfer and thermal management studies of lithium polymer batteries for electric vehicle applications

NASA Astrophysics Data System (ADS)

Song, Li

The thermal conductivities of the polymer electrolyte and composite cathode are important parameters characterizing heat transport in lithium polymer batteries. The thermal conductivities of lithium polymer electrolytes, including poly-ethylene oxide (PEO), PEO-LiClO4, PEO-LiCF3SO 3, PEO-LiN(CF3SO2)2, PEO-LiC(CF 3SO2)3, and the thermal conductivities of TiS 2 and V6O13 composite cathodes, were measured over the temperature range from 25°C to 150°C by a guarded heat flow meter. The thermal conductivities of the electrolytes were found to be relatively constant for the temperature and for electrolytes with various concentrations of the lithium salt. The thermal conductivities of the composite cathodes were found to increase with the temperature below the melting temperature of the polymer electrolyte and only slightly increase above the melting temperature. Three different lithium polymer cells, including Li/PEO-LiCF3 S O3/TiS2, Li/PEO-LiC(CF3 S O2)3/V6 O13, and Li/PEO-LiN(CF3 S O2)2/ Li1+x Mn2 O4 were prepared and their discharge curves, along with heat generation rates, were measured at various galvanostatic discharge current densities, and at different temperature (70°C, 80°C and 90°C), by a potentiostat/galvanostat and an isothermal microcalorimeter. The thermal stability of a lithium polymer battery was examined by a linear perturbation analysis. In contrast to the thermal conductivity, the ionic conductivity of polymer electrolytes for lithium-polymer cell increases greatly with increasing temperature, an instability could arise from this temperature dependence. The numerical calculations, using a two dimensional thermal model, were carried out for constant potential drop across the electrolyte, for constant mean current density and for constant mean cell output power. The numerical calculations were approximately in agreement with the linear perturbation analysis. A coupled mathematical model, including electrochemical and thermal components, was developed to study the heat transfer and thermal management of lithium polymer batteries. The results calculated from the model, including temperature distributions, and temperatures at different stages of discharge are significantly different from those calculated from the thermal model. The discharge curves and heat generation rates calculated by the electrochemical-thermal model were in agreement with the experimental results. Different thermal management approaches, including a variable conductance insulation enclosure were studied.

Joint carbon footprint assessment and data envelopment analysis for the reduction of greenhouse gas emissions in agriculture production.

PubMed

Rebolledo-Leiva, Ricardo; Angulo-Meza, Lidia; Iriarte, Alfredo; González-Araya, Marcela C

2017-09-01

Operations management tools are critical in the process of evaluating and implementing action towards a low carbon production. Currently, a sustainable production implies both an efficient resource use and the obligation to meet targets for reducing greenhouse gas (GHG) emissions. The carbon footprint (CF) tool allows estimating the overall amount of GHG emissions associated with a product or activity throughout its life cycle. In this paper, we propose a four-step method for a joint use of CF assessment and Data Envelopment Analysis (DEA). Following the eco-efficiency definition, which is the delivery of goods using fewer resources and with decreasing environmental impact, we use an output oriented DEA model to maximize production and reduce CF, taking into account simultaneously the economic and ecological perspectives. In another step, we stablish targets for the contributing CF factors in order to achieve CF reduction. The proposed method was applied to assess the eco-efficiency of five organic blueberry orchards throughout three growing seasons. The results show that this method is a practical tool for determining eco-efficiency and reducing GHG emissions. Copyright © 2017 Elsevier B.V. All rights reserved.

Numerical study of He/CF{sub 3}I pulsed discharge used to produce iodine atom in chemical oxygen-iodine laser

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

Zhang Jiao; Wang Yanhui; Wang Dezhen

2013-04-15

The pulsed discharge for producing iodine atoms from the alkyl and perfluoroalky iodides (CH{sub 3}I, CF{sub 3}I, etc.) is the most efficient method for achieving the pulse operating mode of a chemical oxygen-iodine laser. In this paper, a one-dimensional fluid model is developed to study the characteristics of pulsed discharge in CF{sub 3}I-He mixture. By solving continuity equation, momentum equation, Poisson equation, Boltzmann equation, and an electric circuit equation, the temporal evolution of discharge current density and various discharge products, especially the atomic iodine, are investigated. The dependence of iodine atom density on discharge parameters is also studied. The resultsmore » show that iodine atom density increases with the pulsed width and pulsed voltage amplitude. The mixture ratio of CF{sub 3}I and helium plays a more significant role in iodine atom production. For a constant voltage amplitude, there exists an optimal mixture ratio under which the maximum iodine atom concentration is achieved. The bigger the applied voltage amplitude is, the higher partial pressure of CF{sub 3}I is needed to obtain the maximum iodine atom concentration.« less

Counterfactual thinking in patients with amnesia

PubMed Central

Mullally, Sinéad L; Maguire, Eleanor A

2014-01-01

We often engage in counterfactual (CF) thinking, which involves reflecting on “what might have been.” Creating alternative versions of reality seems to have parallels with recollecting the past and imagining the future in requiring the simulation of internally generated models of complex events. Given that episodic memory and imagining the future are impaired in patients with hippocampal damage and amnesia, we wondered whether successful CF thinking also depends upon the integrity of the hippocampus. Here using two nonepisodic CF thinking tasks, we found that patients with bilateral hippocampal damage and amnesia performed comparably with matched controls. They could deconstruct reality, add in and recombine elements, change relations between temporal sequences of events, enabling them to determine plausible alternatives of complex episodes. A difference between the patients and control participants was evident, however, in the patients' subtle avoidance of CF simulations that required the construction of an internal spatial representation. Overall, our findings suggest that mental simulation in the form of nonepisodic CF thinking does not seem to depend upon the hippocampus unless there is the added requirement for construction of a coherent spatial scene within which to play out scenarios. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc. PMID:24978690

Wind and boundary layers in Rayleigh-Bénard convection. II. Boundary layer character and scaling.

PubMed

van Reeuwijk, Maarten; Jonker, Harm J J; Hanjalić, Kemo

2008-03-01

The scaling of the kinematic boundary layer thickness lambda(u) and the friction factor C(f) at the top and bottom walls of Rayleigh-Bénard convection is studied by direct numerical simulation (DNS). By a detailed analysis of the friction factor, a new parameterisation for C(f) and lambda(u) is proposed. The simulations were made of an L/H=4 aspect-ratio domain with periodic lateral boundary conditions at Ra=(10(5), 10(6), 10(7), 10(8)) and Pr=1. The continuous spectrum, as well as significant forcing due to Reynolds stresses, clearly indicates a turbulent character of the boundary layer, while viscous effects cannot be neglected, judging from the scaling of classical integral boundary layer parameters with Reynolds number. Using a conceptual wind model, we find that the friction factor C(f) should scale proportionally to the thermal boundary layer thickness as C(f) proportional variant lambda(Theta)/H, while the kinetic boundary layer thickness lambda(u) scales inversely proportionally to the thermal boundary layer thickness and wind Reynolds number lambda(u)/H proportional variant (lambda(Theta)/H)(-1)Re(-1). The predicted trends for C(f) and lambda(u) are in agreement with DNS results.

Counterfactual thinking in patients with amnesia.

PubMed

Mullally, Sinéad L; Maguire, Eleanor A

2014-11-01

We often engage in counterfactual (CF) thinking, which involves reflecting on "what might have been." Creating alternative versions of reality seems to have parallels with recollecting the past and imagining the future in requiring the simulation of internally generated models of complex events. Given that episodic memory and imagining the future are impaired in patients with hippocampal damage and amnesia, we wondered whether successful CF thinking also depends upon the integrity of the hippocampus. Here using two nonepisodic CF thinking tasks, we found that patients with bilateral hippocampal damage and amnesia performed comparably with matched controls. They could deconstruct reality, add in and recombine elements, change relations between temporal sequences of events, enabling them to determine plausible alternatives of complex episodes. A difference between the patients and control participants was evident, however, in the patients' subtle avoidance of CF simulations that required the construction of an internal spatial representation. Overall, our findings suggest that mental simulation in the form of nonepisodic CF thinking does not seem to depend upon the hippocampus unless there is the added requirement for construction of a coherent spatial scene within which to play out scenarios. Copyright © 2014 THE AUTHORS. HIPPOCAMPUS PUBLISHED BY WILEY PERIODICALS, INC.

Advanced light microscopy core facilities: Balancing service, science and career

PubMed Central

Hartmann, Hella; Reymann, Jürgen; Ansari, Nariman; Utz, Nadine; Fried, Hans‐Ulrich; Kukat, Christian; Peychl, Jan; Liebig, Christian; Terjung, Stefan; Laketa, Vibor; Sporbert, Anje; Weidtkamp‐Peters, Stefanie; Schauss, Astrid; Zuschratter, Werner; Avilov, Sergiy

2016-01-01

ABSTRACT Core Facilities (CF) for advanced light microscopy (ALM) have become indispensable support units for research in the life sciences. Their organizational structure and technical characteristics are quite diverse, although the tasks they pursue and the services they offer are similar. Therefore, throughout Europe, scientists from ALM‐CFs are forming networks to promote interactions and discuss best practice models. Here, we present recommendations for ALM‐CF operations elaborated by the workgroups of the German network of ALM‐CFs, German Bio‐Imaging (GerBI). We address technical aspects of CF planning and instrument maintainance, give advice on the organization and management of an ALM‐CF, propose a scheme for the training of CF users, and provide an overview of current resources for image processing and analysis. Further, we elaborate on the new challenges and opportunities for professional development and careers created by CFs. While some information specifically refers to the German academic system, most of the content of this article is of general interest for CFs in the life sciences. Microsc. Res. Tech. 79:463–479, 2016. © 2016 THE AUTHORS MICROSCOPY RESEARCH AND TECHNIQUE PUBLISHED BY WILEY PERIODICALS, INC. PMID:27040755

Airway inflammation in cystic fibrosis: molecular mechanisms and clinical implications.

PubMed

Cohen-Cymberknoh, Malena; Kerem, Eitan; Ferkol, Thomas; Elizur, Arnon

2013-12-01

Airway epithelial cells and immune cells participate in the inflammatory process responsible for much of the pathology found in the lung of patients with cystic fibrosis (CF). Intense bronchial neutrophilic inflammation and release of proteases and oxygen radicals perpetuate the vicious cycle and progressively damage the airways. In vitro studies suggest that CF transmembrane conductance regulator (CFTR)-deficient airway epithelial cells display signalling abnormalities and aberrant intracellular processes which lead to transcription of inflammatory mediators. Several transcription factors, especially nuclear factor-κB, are activated. In addition, the accumulation of abnormally processed CFTR in the endoplasmic reticulum results in unfolded protein responses that trigger 'cell stress' and apoptosis leading to dysregulation of the epithelial cells and innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation. Measuring airway inflammation is crucial for initiating treatment and monitoring its effect. No inflammatory biomarker predictive for the clinical course of CF lung disease is currently known, although neutrophil elastase seems to correlate with lung function decline. CF animal models mimicking human lung disease may provide an important insight into the pathogenesis of lung inflammation in CF and identify new therapeutic targets.

Advanced light microscopy core facilities: Balancing service, science and career.

PubMed

Ferrando-May, Elisa; Hartmann, Hella; Reymann, Jürgen; Ansari, Nariman; Utz, Nadine; Fried, Hans-Ulrich; Kukat, Christian; Peychl, Jan; Liebig, Christian; Terjung, Stefan; Laketa, Vibor; Sporbert, Anje; Weidtkamp-Peters, Stefanie; Schauss, Astrid; Zuschratter, Werner; Avilov, Sergiy

2016-06-01

Core Facilities (CF) for advanced light microscopy (ALM) have become indispensable support units for research in the life sciences. Their organizational structure and technical characteristics are quite diverse, although the tasks they pursue and the services they offer are similar. Therefore, throughout Europe, scientists from ALM-CFs are forming networks to promote interactions and discuss best practice models. Here, we present recommendations for ALM-CF operations elaborated by the workgroups of the German network of ALM-CFs, German Bio-Imaging (GerBI). We address technical aspects of CF planning and instrument maintainance, give advice on the organization and management of an ALM-CF, propose a scheme for the training of CF users, and provide an overview of current resources for image processing and analysis. Further, we elaborate on the new challenges and opportunities for professional development and careers created by CFs. While some information specifically refers to the German academic system, most of the content of this article is of general interest for CFs in the life sciences. Microsc. Res. Tech. 79:463-479, 2016. © 2016 THE AUTHORS MICROSCOPY RESEARCH AND TECHNIQUE PUBLISHED BY WILEY PERIODICALS, INC. © 2016 The Authors Microscopy Research and Technique Published by Wiley Periodicals, Inc.

Paraoxonase 2 Serves a Proapopotic Function in Mouse and Human Cells in Response to the Pseudomonas aeruginosa Quorum-sensing Molecule N-(3-Oxododecanoyl)-homoserine Lactone*

PubMed Central

Schwarzer, Christian; Fu, Zhu; Morita, Takeshi; Whitt, Aaron G.; Neely, Aaron M.; Li, Chi; Machen, Terry E.

2015-01-01

Pseudomonas aeruginosa use quorum-sensing molecules, including N-(3-oxododecanoyl)-homoserine lactone (C12), for intercellular communication. C12 activated apoptosis in mouse embryo fibroblasts (MEF) from both wild type (WT) and Bax/Bak double knock-out mice (WT MEF and DKO MEF that were responsive to C12, DKOR MEF): nuclei fragmented; mitochondrial membrane potential (Δψmito) depolarized; Ca2+ was released from the endoplasmic reticulum (ER), increasing cytosolic [Ca2+] (Cacyto); and caspase 3/7 was activated. DKOR MEF had been isolated from a nonclonal pool of DKO MEF that were non-responsive to C12 (DKONR MEF). RNAseq analysis, quantitative PCR, and Western blots showed that WT and DKOR MEF both expressed genes associated with cancer, including paraoxonase 2 (PON2), whereas DKONR MEF expressed little PON2. Adenovirus-mediated expression of human PON2 in DKONR MEF rendered them responsive to C12: Δψmito depolarized, Cacyto increased, and caspase 3/7 activated. Human embryonic kidney 293T (HEK293T) cells expressed low levels of endogenous PON2, and these cells were also less responsive to C12. Overexpression of PON2, but not PON2-H114Q (no lactonase activity) in HEK293T cells caused them to become sensitive to C12. Because [C12] may reach high levels in biofilms in lungs of cystic fibrosis (CF) patients, PON2 lactonase activity may control Δψmito, Ca2+ release from the ER, and apoptosis in CF airway epithelia. Coupled with previous data, these results also indicate that PON2 uses its lactonase activity to prevent Bax- and Bak-dependent apoptosis in response to common proapoptotic drugs like doxorubicin and staurosporine, but activates Bax- and Bak-independent apoptosis in response to C12. PMID:25627690

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...

An Inviscid Computational Study of the Space Shuttle Orbiter and Several Damaged Configurations

NASA Technical Reports Server (NTRS)

Prabhu, Ramadas K.; Merski, N. Ronald (Technical Monitor)

2004-01-01

Inviscid aerodynamic characteristics of the Space Shuttle Orbiter were computed in support of the Columbia Accident Investigation. The unstructured grid software FELISA was used and computations were done using freestream conditions corresponding to those in the NASA Langley 20-Inch Mach 6 CF4 tunnel test section. The angle of attack was held constant at 40 degrees. The baseline (undamaged) configuration and a large number of damaged configurations of the Orbiter were studied. Most of the computations were done on a half model. However, one set of computations was done using the full-model to study the effect of sideslip. The differences in the aerodynamic coefficients for the damaged and the baseline configurations were computed. Simultaneously with the computation reported here, tests were being done on a scale model of the Orbiter in the 20-Inch Mach 6 CF4 tunnel to measure the deltas . The present computations complemented the CF4 tunnel test, and provided aerodynamic coefficients of the Orbiter as well as its components. Further, they also provided details of the flow field.

An LCA researcher's wish list--data and emission models needed to improve LCA studies of animal production.

PubMed

Cederberg, C; Henriksson, M; Berglund, M

2013-06-01

The last decade has seen an increase in environmental systems analysis of livestock production, resulting in a significant number of studies with a holistic approach often based on life-cycle assessment (LCA) methodology. The growing public interest in global warming has added to this development; guidelines for carbon footprint (CF) accounting have been developed, including for greenhouse gas (GHG) accounting of animal products. Here we give an overview of methods for estimating GHG emissions, with emphasis on nitrous oxide, methane and carbon from land use change, presently used in LCA/CF studies of animal products. We discuss where methods and data availability for GHGs and nitrogen (N) compounds most urgently need to be improved in order to produce more accurate environmental assessments of livestock production. We conclude that the top priority is to improve models for N fluxes and emissions from soils and to implement soil carbon change models in LCA/CF studies of animal products. We also point at the need for more farm data and studies measuring emissions from soils, manure and livestock in developing countries.

Cross-correlation measurements with the EJ-299-33 plastic scintillator

NASA Astrophysics Data System (ADS)

Bourne, Mark M.; Whaley, Jeff; Dolan, Jennifer L.; Polack, John K.; Flaska, Marek; Clarke, Shaun D.; Tomanin, Alice; Peerani, Paolo; Pozzi, Sara A.

2015-06-01

New organic-plastic scintillation compositions have demonstrated pulse-shape discrimination (PSD) of neutrons and gamma rays. We present cross-correlation measurements of 252Cf and mixed uranium-plutonium oxide (MOX) with the EJ-299-33 plastic scintillator. For comparison, equivalent measurements were performed with an EJ-309 liquid scintillator. Offline, digital PSD was applied to each detector. These measurements show that EJ-299-33 sacrifices a factor of 5 in neutron-neutron efficiency relative to EJ-309, but could still utilize the difference in neutron-neutron efficiency and neutron single-to-double ratio to distinguish 252Cf from MOX. These measurements were modeled with MCNPX-PoliMi, and MPPost was used to convert the detailed collision history into simulated cross-correlation distributions. MCNPX-PoliMi predicted the measured 252Cf cross-correlation distribution for EJ-309 to within 10%. Greater photon uncertainty in the MOX sample led to larger discrepancy in the simulated MOX cross-correlation distribution. The modeled EJ-299-33 plastic also gives reasonable agreement with measured cross-correlation distributions, although the MCNPX-PoliMi model appears to under-predict the neutron detection efficiency.

Theoretical research of the spin-Hamiltonian parameters for two rhombic W5+ centers in KTiOPO4 (KTP) crystal through a two-mechanism model

NASA Astrophysics Data System (ADS)

Mei, Yang; Chen, Bo-Wei; Wei, Chen-Fu; Zheng, Wen-Chen

2016-09-01

The high-order perturbation formulas based on the two-mechanism model are employed to calculate the spin-Hamiltonian parameters (g factors gi and hyperfine structure constants Ai, where i=x, y, z) for two approximately rhombic W5+ centers in KTiOPO4 (KTP) crystal. In the model, both the widely-applied crystal-field (CF) mechanism concerning the interactions of CF excited states with the ground state and the generally-neglected charge-transfer (CT) mechanism concerning the interactions of CT excited states with the ground state are included. The calculated results agree with the experimental values, and the signs of constants Ai are suggested. The calculations indicate that (i) for the high valence state dn ions in crystals, the contributions to spin-Hamiltonian parameters should take into account both the CF and CT mechanisms and (ii) the large g-shifts |Δgi | (=|gi-ge |, where ge≈ 2.0023) for W5+ centers in crystals are due to the large spin-orbit parameter of free W5+ ion.

Occupancy modeling and estimation of the holiday darter species complex within the Etowah River system

USGS Publications Warehouse

Anderson, Gregory B.; Freeman, Mary C.; Hagler, Megan M.; Freeman, Byron J.

2012-01-01

Documenting the status of rare fishes is a crucial step in effectively managing populations and implementing regulatory mechanisms of protection. In recent years, site occupancy has become an increasingly popular metric for assessing populations, but species distribution models that do not account for imperfect detection can underestimate the proportion of sites occupied and the strength of the relationship with a hypothesized covariate. However, valid detection requires temporal or spatial replication, which is often not feasible due to logistical or budget constraints. In this study, we used a method that allowed for spatial replication during a single visit to evaluate the current status of the holiday darter species complex, Etheostoma sp. cf. E. brevirostrum, within the Etowah River system. Moreover, the modeling approach used in this study facilitated comparisons of factors influencing stream occupancy as well as species detection within sites. The results suggest that there is less habitat available for the Etowah holiday darter form (Etheostoma sp. cf. E. brevirostrum B) than for the Amicalola holiday darter form (Etheostoma sp. cf. E. brevirostrum A). Additionally, occupancy models suggest that even small decreases in forest cover within these headwater systems adversely affect holiday darter populations.

Neonatal injury at cephalic vaginal delivery: a retrospective analysis of extent of association with shoulder dystocia.

PubMed

Iskender, Cantekin; Kaymak, Oktay; Erkenekli, Kudret; Ustunyurt, Emin; Uygur, Dilek; Yakut, Halil Ibrahim; Danisman, Nuri

2014-01-01

To describe the risk factors and labor characteristics of Clavicular fracture (CF) and brachial plexus injury (BPI); and compare antenatal and labor characteristics and prognosis of obstetrical BPI associated with shoulder dystocia with obstetrical BPI not associated with shoulder dystocia. This retrospective study consisted of women who gave birth to an infant with a fractured clavicle or BPI between January 2009 and June 2013. Antenatal and neonatal data were compared between groups. The control group (1300) was composed of the four singleton vaginal deliveries that immediately followed each birth injury. A multivariable logistic regression model, with backward elimination, was constructed in order to find independent risk factors associated with BPI and CF. A subgroup analysis involved comparison of features of BPI cases with or without associated shoulder dystocia. During the study period, the total number of vaginal deliveries was 44092. The rates of CF, BPI and shoulder dystocia during the study period were 0,6%, 0,16% and 0,29%, respectively. In the logistic regression model, shoulder dystocia, GDM, multiparity, gestational age >42 weeks, protracted labor, short second stage of labor and fetal birth weight greater than 4250 grams increased the risk of CF independently. Shoulder dystocia and protracted labor were independently associated with BPI when controlled for other factors. Among neonates with BPI whose injury was not associated with shoulder dystocia, five (12.2%) sustained permanent injury, whereas one neonate (4.5%) with BPI following shoulder dystocia sustained permanent injury (p = 0.34). BPI not associated with shoulder dystocia might have a higher rate of concomitant CF and permanent sequelae.

Transducing Airway Basal Cells with a Helper-Dependent Adenoviral Vector for Lung Gene Therapy.

PubMed

Cao, Huibi; Ouyang, Hong; Grasemann, Hartmut; Bartlett, Claire; Du, Kai; Duan, Rongqi; Shi, Fushan; Estrada, Marvin; Seigel, Kyle E; Coates, Allan L; Yeger, Herman; Bear, Christine E; Gonska, Tanja; Moraes, Theo J; Hu, Jim

2018-06-01

A major challenge in developing gene-based therapies for airway diseases such as cystic fibrosis (CF) is sustaining therapeutic levels of transgene expression over time. This is largely due to airway epithelial cell turnover and the host immunogenicity to gene delivery vectors. Modern gene editing tools and delivery vehicles hold great potential for overcoming this challenge. There is currently not much known about how to deliver genes into airway stem cells, of which basal cells are the major type in human airways. In this study, helper-dependent adenoviral (HD-Ad) vectors were delivered to mouse and pig airways via intranasal delivery, and direct bronchoscopic instillation, respectively. Vector transduction was assessed by immunostaining of lung tissue sections, which revealed that airway basal cells of mice and pigs can be targeted in vivo. In addition, efficient transduction of primary human airway basal cells was verified with an HD-Ad vector expressing green fluorescent protein. Furthermore, we successfully delivered the human CFTR gene to airway basal cells from CF patients, and demonstrated restoration of CFTR channel activity following cell differentiation in air-liquid interface culture. Our results provide a strong rationale for utilizing HD-Ad vectors to target airway basal cells for permanent gene correction of genetic airway diseases.

Biofilm Filtrates of Pseudomonas aeruginosa Strains Isolated from Cystic Fibrosis Patients Inhibit Preformed Aspergillus fumigatus Biofilms via Apoptosis

PubMed Central

Shirazi, Fazal; Ferreira, Jose A. G.; Stevens, David A.; Clemons, Karl V.; Kontoyiannis, Dimitrios P.

2016-01-01

Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) colonize cystic fibrosis (CF) patient airways. Pa culture filtrates inhibit Af biofilms, and Pa non-CF, mucoid (Muc-CF) and nonmucoid CF (NMuc-CF) isolates form an ascending inhibitory hierarchy. We hypothesized this activity is mediated through apoptosis induction. One Af and three Pa (non-CF, Muc-CF, NMuc-CF) reference isolates were studied. Af biofilm was formed in 96 well plates for 16 h ± Pa biofilm filtrates. After 24 h, apoptosis was characterized by viability dye DiBAc, reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, DNA fragmentation and metacaspase activity. Muc-CF and NMuc-CF filtrates inhibited and damaged Af biofilm (p<0.0001). Intracellular ROS levels were elevated (p<0.001) in NMuc-CF-treated Af biofilms (3.7- fold) compared to treatment with filtrates from Muc-CF- (2.5- fold) or non-CF Pa (1.7- fold). Depolarization of mitochondrial potential was greater upon exposure to NMuc-CF (2.4-fold) compared to Muc-CF (1.8-fold) or non-CF (1.25-fold) (p<0.0001) filtrates. Exposure to filtrates resulted in more DNA fragmentation in Af biofilm, compared to control, mediated by metacaspase activation. In conclusion, filtrates from CF-Pa isolates were more inhibitory against Af biofilms than from non-CF. The apoptotic effect involves mitochondrial membrane damage associated with metacaspase activation. PMID:26930399

Biofilm Filtrates of Pseudomonas aeruginosa Strains Isolated from Cystic Fibrosis Patients Inhibit Preformed Aspergillus fumigatus Biofilms via Apoptosis.

PubMed

Shirazi, Fazal; Ferreira, Jose A G; Stevens, David A; Clemons, Karl V; Kontoyiannis, Dimitrios P

2016-01-01

Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) colonize cystic fibrosis (CF) patient airways. Pa culture filtrates inhibit Af biofilms, and Pa non-CF, mucoid (Muc-CF) and nonmucoid CF (NMuc-CF) isolates form an ascending inhibitory hierarchy. We hypothesized this activity is mediated through apoptosis induction. One Af and three Pa (non-CF, Muc-CF, NMuc-CF) reference isolates were studied. Af biofilm was formed in 96 well plates for 16 h ± Pa biofilm filtrates. After 24 h, apoptosis was characterized by viability dye DiBAc, reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, DNA fragmentation and metacaspase activity. Muc-CF and NMuc-CF filtrates inhibited and damaged Af biofilm (p<0.0001). Intracellular ROS levels were elevated (p<0.001) in NMuc-CF-treated Af biofilms (3.7- fold) compared to treatment with filtrates from Muc-CF- (2.5- fold) or non-CF Pa (1.7- fold). Depolarization of mitochondrial potential was greater upon exposure to NMuc-CF (2.4-fold) compared to Muc-CF (1.8-fold) or non-CF (1.25-fold) (p<0.0001) filtrates. Exposure to filtrates resulted in more DNA fragmentation in Af biofilm, compared to control, mediated by metacaspase activation. In conclusion, filtrates from CF-Pa isolates were more inhibitory against Af biofilms than from non-CF. The apoptotic effect involves mitochondrial membrane damage associated with metacaspase activation.

Epidemiology of Cystic Fibrosis.

PubMed

Spoonhower, Kimberly A; Davis, Pamela B

2016-03-01

Improved quality of care and rapidly emerging therapeutic strategies to restore chloride transport profoundly impact the epidemiology and pathobiology of cystic fibrosis (CF) in the twenty-first century. CF now serves as a model for chronic illness management, continuous quality improvement via registry data, and a seamless link between basic science research, translational studies, clinical trials, and outcomes research to enable rapid expansion of treatment options. Copyright © 2016 Elsevier Inc. All rights reserved.

Global emissions of the hydrofluorocarbons (HFCs) HFC-365mfc, HFC-245fa, HFC-227ea, and HFC-236fa based on atmospheric observations

NASA Astrophysics Data System (ADS)

Vollmer, M. K.; Miller, B. R.; Rigby, M. L.; Reimann, S.; Muhle, J.; Agage, Soge, Snu Members, Kopri Members

2010-12-01

We report on the atmospheric measurements and global emissions of the hydrofluorocarbons (HFCs) HFC-365mfc (CH3CH2CF2CF3, 1,1,1,3,3-pentafluorobutane), HFC-245fa (CHF2CH2CF3, 1,1,1,3,3-pentafluoropropane), HFC-227ea (CF3CHFCF3, 1,1,1,2,3,3,3-heptafluoropropane), and HFC-236fa (CF3CH2CF3, 1,1,1,3,3,3-hexafluoropropane). These measurements are from in-situ observations at stations of AGAGE (Advanced Global Atmospheric Gases Experiment) and SOGE (System for Observations of Halogenated Greenhouse Gases in Europe), and from the Korean station Gosan. We also report on flask sample measurements from the Antarctic stations King Sejong and Troll, and extend our records back to the 1970s using archived air samples of both hemispheres. All data are used in a global 12-box 2-dimensional atmospheric transport model to derive global abundances and emission estimates. All four HFCs have strongly increased in the atmosphere in recent years with growth rates at nearly 10 %, resulting in dry air mole fractions at the end of 2009 of 0.49 ppt for HFC-365mfc, 1.00 ppt for HFC-245fa, and 0.51 ppt for HFC-227ea. HFC-236fa, for which we report the first atmospheric measurements, is less abundant and has grown to 0.069 ppt at the end of 2009. Our model results show rapidly growing emissions of HFC-365mfc and HFC-245fa after 2002 but surprisingly these have now started to decline to globally 2.7 kt/yr (HFC-365mfc) and 6.1 kt/yr (HFC-245fa). On the other hand HFC-227ea and HFC-236fa show uninterrupted growth in their emissions of 2.5 kt/yr and 0.2 kt/yr at the end of 2009.

Double-letter processing in surface dyslexia and dysgraphia following a left temporal lesion: A multimodal neuroimaging study.

PubMed

Tomasino, Barbara; Marin, Dario; Maieron, Marta; D'Agostini, Serena; Fabbro, Franco; Skrap, Miran; Luzzatti, Claudio

2015-12-01

Neuropsychological data about acquired impairments in reading and writing provide a strong basis for the theoretical framework of the dual-route models. The present study explored the functional neuroanatomy of the reading and spelling processing system. We describe the reading and writing performance of patient CF, an Italian native speaker who developed an extremely selective reading and spelling deficit (his spontaneous speech, oral comprehension, repetition and oral picture naming were almost unimpaired) in processing double letters associated with surface dyslexia and dysgraphia, following a tumor in the left temporal lobe. In particular, the majority of CF's errors in spelling were phonologically plausible substitutions, errors concerning letter numerosity of consonants, and syllabic phoneme-to-grapheme conversion (PGC) errors. A similar pattern of impairment also emerged in his reading behavior, with a majority of lexical stress errors (the only possible type of surface reading errors in the Italian language, due the extreme regularity of print-to-sound correspondence). CF's neuropsychological profile was combined with structural neuroimaging data, fiber tracking, and functional maps and compared to that of healthy control participants. We related CF's deficit to a dissociation between impaired ventral/lexical route (as evidenced by a fractional anisotropy - FA decrease along the inferior fronto-occipital fasciculus - IFOF) and relatively preserved dorsal/phonological route (as evidenced by a rather full integrity of the superior longitudinal fasciculus - SLF). In terms of functional processing, the lexical-semantic ventral route network was more activated in controls than in CF, while the network supporting the dorsal route was shared by CF and the control participants. Our results are discussed within the theoretical framework of dual-route models of reading and spelling, emphasize the importance of the IFOF both in lexical reading and spelling, and offer a better comprehension of the neurological and functional substrates involved in written language and, in particular, in surface dyslexia and dysgraphia and in doubling/de-doubling consonant sounds and letters. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular Modeling of Aerospace Polymer Matrices Including Carbon Nanotube-Enhanced Epoxy

NASA Astrophysics Data System (ADS)

Radue, Matthew S.

Carbon fiber (CF) composites are increasingly replacing metals used in major structural parts of aircraft, spacecraft, and automobiles. The current limitations of carbon fiber composites are addressed through computational material design by modeling the salient aerospace matrix materials. Molecular Dynamics (MD) models of epoxies with and without carbon nanotube (CNT) reinforcement and models of pure bismaleimides (BMIs) were developed to elucidate structure-property relationships for improved selection and tailoring of matrices. The influence of monomer functionality on the mechanical properties of epoxies is studied using the Reax Force Field (ReaxFF). From deformation simulations, the Young's modulus, yield point, and Poisson's ratio are calculated and analyzed. The results demonstrate an increase in stiffness and yield strength with increasing resin functionality. Comparison between the network structures of distinct epoxies is further advanced by the Monomeric Degree Index (MDI). Experimental validation demonstrates the MD results correctly predict the relationship in Young's moduli for all epoxies modeled. Therefore, the ReaxFF is confirmed to be a useful tool for studying the mechanical behavior of epoxies. While epoxies have been well-studied using MD, there has been no concerted effort to model cured BMI polymers due to the complexity of the network-forming reactions. A novel, adaptable crosslinking framework is developed for implementing 5 distinct cure reactions of Matrimid-5292 (a BMI resin) and investigating the network structure using MD simulations. The influence of different cure reactions and extent of curing are analyzed on the several thermo-mechanical properties such as mass density, glass transition temperature, coefficient of thermal expansion, elastic moduli, and thermal conductivity. The developed crosslinked models correctly predict experimentally observed trends for various properties. Finally, the epoxies modeled (di-, tri-, and tetra-functionalresins) are simulated with embedded CNT to understand how the affinity to nanoparticles affects the mechanical response. Multiscale modeling techniques are then employed to translate the molecular phenomena observed to predict the behavior of realistic composites. The effective stiffness of hybrid composites are predicted for CNT/epoxy composites with randomly oriented CNTs, for CF/CNT/epoxy systems with aligned CFs and randomly oriented CNTs, and for woven CF/CNT/epoxy fabric with randomly oriented CNTs. The results indicate that in the CNT/epoxy systems the epoxy type has a significant influence on the elastic properties. For the CF/CNT/epoxy hybrid composites, the axial modulus is highly influenced by CF concentration, while the transverse modulus is primarily affected by the CNT weight fraction.

A bi-hemispheric neuronal network model of the cerebellum with spontaneous climbing fiber firing produces asymmetrical motor learning during robot control.

PubMed

Pinzon-Morales, Ruben-Dario; Hirata, Yutaka

2014-01-01

To acquire and maintain precise movement controls over a lifespan, changes in the physical and physiological characteristics of muscles must be compensated for adaptively. The cerebellum plays a crucial role in such adaptation. Changes in muscle characteristics are not always symmetrical. For example, it is unlikely that muscles that bend and straighten a joint will change to the same degree. Thus, different (i.e., asymmetrical) adaptation is required for bending and straightening motions. To date, little is known about the role of the cerebellum in asymmetrical adaptation. Here, we investigate the cerebellar mechanisms required for asymmetrical adaptation using a bi-hemispheric cerebellar neuronal network model (biCNN). The bi-hemispheric structure is inspired by the observation that lesioning one hemisphere reduces motor performance asymmetrically. The biCNN model was constructed to run in real-time and used to control an unstable two-wheeled balancing robot. The load of the robot and its environment were modified to create asymmetrical perturbations. Plasticity at parallel fiber-Purkinje cell synapses in the biCNN model was driven by error signal in the climbing fiber (cf) input. This cf input was configured to increase and decrease its firing rate from its spontaneous firing rate (approximately 1 Hz) with sensory errors in the preferred and non-preferred direction of each hemisphere, as demonstrated in the monkey cerebellum. Our results showed that asymmetrical conditions were successfully handled by the biCNN model, in contrast to a single hemisphere model or a classical non-adaptive proportional and derivative controller. Further, the spontaneous activity of the cf, while relatively small, was critical for balancing the contribution of each cerebellar hemisphere to the overall motor command sent to the robot. Eliminating the spontaneous activity compromised the asymmetrical learning capabilities of the biCNN model. Thus, we conclude that a bi-hemispheric structure and adequate spontaneous activity of cf inputs are critical for cerebellar asymmetrical motor learning.

A bi-hemispheric neuronal network model of the cerebellum with spontaneous climbing fiber firing produces asymmetrical motor learning during robot control

PubMed Central

Pinzon-Morales, Ruben-Dario; Hirata, Yutaka

2014-01-01

To acquire and maintain precise movement controls over a lifespan, changes in the physical and physiological characteristics of muscles must be compensated for adaptively. The cerebellum plays a crucial role in such adaptation. Changes in muscle characteristics are not always symmetrical. For example, it is unlikely that muscles that bend and straighten a joint will change to the same degree. Thus, different (i.e., asymmetrical) adaptation is required for bending and straightening motions. To date, little is known about the role of the cerebellum in asymmetrical adaptation. Here, we investigate the cerebellar mechanisms required for asymmetrical adaptation using a bi-hemispheric cerebellar neuronal network model (biCNN). The bi-hemispheric structure is inspired by the observation that lesioning one hemisphere reduces motor performance asymmetrically. The biCNN model was constructed to run in real-time and used to control an unstable two-wheeled balancing robot. The load of the robot and its environment were modified to create asymmetrical perturbations. Plasticity at parallel fiber-Purkinje cell synapses in the biCNN model was driven by error signal in the climbing fiber (cf) input. This cf input was configured to increase and decrease its firing rate from its spontaneous firing rate (approximately 1 Hz) with sensory errors in the preferred and non-preferred direction of each hemisphere, as demonstrated in the monkey cerebellum. Our results showed that asymmetrical conditions were successfully handled by the biCNN model, in contrast to a single hemisphere model or a classical non-adaptive proportional and derivative controller. Further, the spontaneous activity of the cf, while relatively small, was critical for balancing the contribution of each cerebellar hemisphere to the overall motor command sent to the robot. Eliminating the spontaneous activity compromised the asymmetrical learning capabilities of the biCNN model. Thus, we conclude that a bi-hemispheric structure and adequate spontaneous activity of cf inputs are critical for cerebellar asymmetrical motor learning. PMID:25414644

Composite fermion theory for bosonic quantum Hall states on lattices.

PubMed

Möller, G; Cooper, N R

2009-09-04

We study the ground states of the Bose-Hubbard model in a uniform magnetic field, motivated by the physics of cold atomic gases on lattices at high vortex density. Mapping the bosons to composite fermions (CF) leads to the prediction of quantum Hall fluids that have no counterpart in the continuum. We construct trial states for these phases and test numerically the predictions of the CF model. We establish the existence of strongly correlated phases beyond those in the continuum limit and provide evidence for a wider scope of the composite fermion approach beyond its application to the lowest Landau level.

Adaptive Correlation Model for Visual Tracking Using Keypoints Matching and Deep Convolutional Feature.

PubMed

Li, Yuankun; Xu, Tingfa; Deng, Honggao; Shi, Guokai; Guo, Jie

2018-02-23

Although correlation filter (CF)-based visual tracking algorithms have achieved appealing results, there are still some problems to be solved. When the target object goes through long-term occlusions or scale variation, the correlation model used in existing CF-based algorithms will inevitably learn some non-target information or partial-target information. In order to avoid model contamination and enhance the adaptability of model updating, we introduce the keypoints matching strategy and adjust the model learning rate dynamically according to the matching score. Moreover, the proposed approach extracts convolutional features from a deep convolutional neural network (DCNN) to accurately estimate the position and scale of the target. Experimental results demonstrate that the proposed tracker has achieved satisfactory performance in a wide range of challenging tracking scenarios.

Resistive switching mechanism in the one diode-one resistor memory based on p+-Si/n-ZnO heterostructure revealed by in-situ TEM

NASA Astrophysics Data System (ADS)

Zhang, Lei; Zhu, Liang; Li, Xiaomei; Xu, Zhi; Wang, Wenlong; Bai, Xuedong

2017-03-01

One diode-one resistor (1D1R) memory is an effective architecture to suppress the crosstalk interference, realizing the crossbar network integration of resistive random access memory (RRAM). Herein, we designed a p+-Si/n-ZnO heterostructure with 1D1R function. Compared with the conventional multilayer 1D1R devices, the structure and fabrication technique can be largely simplified. The real-time imaging of formation/rupture process of conductive filament (CF) process demonstrated the RS mechanism by in-situ transmission electron microscopy (TEM). Meanwhile, we observed that the formed CF is only confined to the outside of depletion region of Si/ZnO pn junction, and the formation of CF does not degrade the diode performance, which allows the coexistence of RS and rectifying behaviors, revealing the 1D1R switching model. Furthermore, it has been confirmed that the CF is consisting of the oxygen vacancy by in-situ TEM characterization.

IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis

PubMed Central

Iannitti, Rossana G.; Napolioni, Valerio; Oikonomou, Vasilis; De Luca, Antonella; Galosi, Claudia; Pariano, Marilena; Massi-Benedetti, Cristina; Borghi, Monica; Puccetti, Matteo; Lucidi, Vincenzina; Colombo, Carla; Fiscarelli, Ersilia; Lass-Flörl, Cornelia; Majo, Fabio; Cariani, Lisa; Russo, Maria; Porcaro, Luigi; Ricciotti, Gabriella; Ellemunter, Helmut; Ratclif, Luigi; De Benedictis, Fernando Maria; Talesa, Vincenzo Nicola; Dinarello, Charles A.; van de Veerdonk, Frank L.; Romani, Luigina

2016-01-01

Dysregulated inflammasome activation contributes to respiratory infections and pathologic airway inflammation. Through basic and translational approaches involving murine models and human genetic epidemiology, we show here the importance of the different inflammasomes in regulating inflammatory responses in mice and humans with cystic fibrosis (CF), a life-threatening disorder of the lungs and digestive system. While both contributing to pathogen clearance, NLRP3 more than NLRC4 contributes to deleterious inflammatory responses in CF and correlates with defective NLRC4-dependent IL-1Ra production. Disease susceptibility in mice and microbial colonization in humans occurrs in conditions of genetic deficiency of NLRC4 or IL-1Ra and can be rescued by administration of the recombinant IL-1Ra, anakinra. These results indicate that pathogenic NLRP3 activity in CF could be negatively regulated by IL-1Ra and provide a proof-of-concept evidence that inflammasomes are potential targets to limit the pathological consequences of microbial colonization in CF. PMID:26972847

Determination of the fraction of excited iodine atoms produced by dissociation of iodides in a self-sustained pulsed discharge

NASA Astrophysics Data System (ADS)

Vagin, N. P.; Kochetov, I. V.; Napartovich, A. P.; Yuryshev, N. N.

2017-12-01

Based on the measured absorption coefficient for the atomic iodine transition in the mixtures of iodides with helium we have determined the fractions of the excited atomic iodine produced by dissociation of CH3I, CF3I, i-C3F7I, C2F5I and C2H5I molecules in a self-sustained pulsed discharge. In the 1: (3 - 15) mixtures of iodides with helium at the pressure 133 - 400 Pa these fractions amount to 0.29 for CF3I and CH3I, 0.2 for i-C3F7I, and 0.31 for C2F5I and C2H5I. The accuracy of determining the excited iodine fraction is 10%. The numerical modelling is carried out for the mixtures containing CF3I. The calculated values of the excited iodine fraction for the mixture with CF3I agree well with the experimental data.

IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis.

PubMed

Iannitti, Rossana G; Napolioni, Valerio; Oikonomou, Vasilis; De Luca, Antonella; Galosi, Claudia; Pariano, Marilena; Massi-Benedetti, Cristina; Borghi, Monica; Puccetti, Matteo; Lucidi, Vincenzina; Colombo, Carla; Fiscarelli, Ersilia; Lass-Flörl, Cornelia; Majo, Fabio; Cariani, Lisa; Russo, Maria; Porcaro, Luigi; Ricciotti, Gabriella; Ellemunter, Helmut; Ratclif, Luigi; De Benedictis, Fernando Maria; Talesa, Vincenzo Nicola; Dinarello, Charles A; van de Veerdonk, Frank L; Romani, Luigina

2016-03-14

Dysregulated inflammasome activation contributes to respiratory infections and pathologic airway inflammation. Through basic and translational approaches involving murine models and human genetic epidemiology, we show here the importance of the different inflammasomes in regulating inflammatory responses in mice and humans with cystic fibrosis (CF), a life-threatening disorder of the lungs and digestive system. While both contributing to pathogen clearance, NLRP3 more than NLRC4 contributes to deleterious inflammatory responses in CF and correlates with defective NLRC4-dependent IL-1Ra production. Disease susceptibility in mice and microbial colonization in humans occurs in conditions of genetic deficiency of NLRC4 or IL-1Ra and can be rescued by administration of the recombinant IL-1Ra, anakinra. These results indicate that pathogenic NLRP3 activity in CF could be negatively regulated by IL-1Ra and provide a proof-of-concept evidence that inflammasomes are potential targets to limit the pathological consequences of microbial colonization in CF.

Pulmonary function in individuals who underwent liver transplantation: from the US cystic fibrosis foundation registry.

PubMed

Miller, Melissa R; Sokol, Ronald J; Narkewicz, Michael R; Sontag, Marci K

2012-05-01

Severe liver disease affects 4.5% to 10% of individuals with cystic fibrosis (CF) and is the third-leading cause of death. Liver transplantation (LT) is an accepted therapy, but the effects of liver disease and LT on pulmonary function in patients with CF are controversial. Our aim was to characterize changes in pulmonary function in LT patients with CF. Using mixed effect models, we analyzed pulmonary function before and after transplantation in 168 LT patients and 840 non-LT patients with CF who were matched by age, sex, pancreatic status, infections with US CF Foundation Patient Registry data (1989-2007). The primary outcome was the change in the forced expiratory volume in 1 second (FEV(1); percent predicted) in LT and non-LT in the 3-years periods before or after transplantation; second we compared FEV(1) changes. In the 3 years before transplantation, LT had lower initial FEV(1) values (71.5% ± 1.9%, P < 0.001) and a slower decline (+0.1% ± 0.4%/year, P < 0.001) than non-LT (79.6% ± 1.3% and -1.3% ± 0.2%/year, respectively). There was no difference in the FEV(1) decline after transplantation (-1.4% ± 0.4%/year for LT versus -2.1% ± 0.2%/year for non-LT, P = 0.14). Both the (P = 0.003) and (P = 0.001) had a slower FEV(1) decline in the period before transplantation versus after transplantation. In conclusion, pulmonary function is lower and declines more slowly in patients with CF before LT versus, but parallels the decline in non-LT after transplantation. LT is neither beneficial nor detrimental to pulmonary function in CF but returns FEV(1) decline to the same trajectory found for matched non-LT individuals with CF. Copyright © 2012 American Association for the Study of Liver Diseases.

Synthesis and characterization of structural, optical, thermal and dielectric properties of polyaniline/CoFe2O4 nanocomposites with special reference to photocatalytic activity.

PubMed

Khan, Javed Alam; Qasim, Mohd; Singh, Braj Raj; Singh, Sneha; Shoeb, Mohd; Khan, Wasi; Das, Dibakar; Naqvi, Alim H

2013-05-15

In this study we have synthesized polyaniline/CoFe2O4 nanocomposites (PANI@CFs) by in situ polymerization method with different amounts of the CoFe2O4 nanoparticles NPs (CF-NPs) (0.5 g and 1.0 g). The structural optical, thermal and dielectric properties of the as synthesized PANI@CFs were studied. The XRD analysis ensures that CF-NPs have a single phase spinel structure. The XRD and EDAX results confirmed that the CF-NPs were successfully incorporated in the PANI matrix. The crystalline size analysis revealed that the size increased with increasing CF-NPs amount in the PANI@CFs, because of the aggregation effect. TGA exhibited an enhanced thermal stability of the PANI@CFs as compare with PANI owing to the strong interaction between the CF-NPs and polymer matrix. The energy band gaps as calculated through the Tauc relation were found to be gradually higher with the increasing the amount of CF-NPs in PANI@CFs. The dielectric constants (ε', ε″), dielectric loss (tanδ) and AC conductivity (σac) were studied as the function of frequency and composition, which have been explained by 'Maxwell Wagner Model'. The high dielectric constant and ac conductivity were observed of PANI@CFs than PANI. Moreover, PANI@CF 1:2 exhibited the promising photocatalytic activity for the photo-decoloration of the methyl orange (MO) dye under UV light irradiation. Results also showed protection of photo-decoloration of the MO dye by the disodium ethylenediaminetetraacetate dehydrate (EDTA-Na2; C10H14N2Na2O8·2H2O) (hole scavenger) and tert-butyl alcohol (C4H10O) (radical scavenger) clearly suggested the implication of reactive oxygen species (ROS) in the photocatalytic activity of PANI@CF 1:2. It is encouraging to conclude that PANI@CF bears the potential of its applications in photocatalysis. Copyright © 2013 Elsevier B.V. All rights reserved.

What follows newborn screening? An evaluation of a residential education program for parents of infants with newly diagnosed cystic fibrosis.

PubMed

Sawyer, Susan M; Glazner, Judith A

2004-08-01

The diagnosis of a severe life-limiting condition, such as cystic fibrosis (CF), is generally followed by assessment and treatment of the child and education and counseling for parents. The introduction of newborn screening for CF provides an opportunity for standardized assessment and education. The aim of this study was to evaluate a 5-day residential assessment and education program for parents of infants who receive a diagnosis of CF after newborn screening. Eligible parents had a 6- to 30-month-old infant with CF diagnosed by newborn screening. Parents were interviewed by telephone using a structured questionnaire that addressed 3 main themes: 1) initial communication of the diagnosis of CF, 2) the perceived value of the 5-day assessment and education program, and 3) the perceived advantages and disadvantages of the residential component (Care-By-Parent unit) of the program. Fifteen of 17 eligible families took part in the 5-day assessment and education program, 12 of whom used the residential Care-By-Parent unit. At the end of the program, parents believed that they had the knowledge and skills required to manage their child's CF at home. One hundred percent endorsed the timing of the assessment and education program immediately after the child's diagnosis and would recommend it to other families in the same situation. Perceived advantages of the residential program were not having to travel (89%), being able to concentrate on CF (50%), and the benefit of a "home base" at the hospital (39%). Twenty-two percent reported that financial costs related to participation (paternal time off work) were a disadvantage, 17% reported additional strain on family members caring for siblings, and 17% mentioned lack of comfort within the unit. This time-intensive residential program was evaluated positively by parents of children with newly diagnosed CF. It provides a model for education programs after the diagnosis of CF by newborn screening, as well as for other pediatric conditions that require intensive parent education.

Intracellular calcium dynamics permit a Purkinje neuron model to perform toggle and gain computations upon its inputs

PubMed Central

Forrest, Michael D.

2014-01-01

Without synaptic input, Purkinje neurons can spontaneously fire in a repeating trimodal pattern that consists of tonic spiking, bursting and quiescence. Climbing fiber input (CF) switches Purkinje neurons out of the trimodal firing pattern and toggles them between a tonic firing and a quiescent state, while setting the gain of their response to Parallel Fiber (PF) input. The basis to this transition is unclear. We investigate it using a biophysical Purkinje cell model under conditions of CF and PF input. The model can replicate these toggle and gain functions, dependent upon a novel account of intracellular calcium dynamics that we hypothesize to be applicable in real Purkinje cells. PMID:25191262

Psychological interventions to reduce suicidality in high-risk patients with major depression: a randomized controlled trial.

PubMed

Celano, C M; Beale, E E; Mastromauro, C A; Stewart, J G; Millstein, R A; Auerbach, R P; Bedoya, C A; Huffman, J C

2017-04-01

Positive psychological constructs have been associated with reduced suicidal ideation, and interventions to cultivate positive feelings have the potential to reduce suicide risk. This study compares the efficacy of a 6-week, telephone-based positive psychology (PP) intervention against a cognition-focused (CF) control intervention among patients recently hospitalized for depression and suicidal ideation or behavior. A total of 65 adults with a current major depressive episode reporting suicidal ideation or a recent suicide attempt were enrolled from participating in-patient psychiatric units. Prior to discharge, participants were randomized to the PP (n = 32) or CF (n = 33) intervention. In both interventions, participants received a treatment manual, performed weekly PP (e.g. gratitude letter) or CF (e.g. recalling daily events) exercises, and completed weekly one-on-one telephone sessions over 6 weeks. Between-group differences in hopelessness (primary outcome), depression, suicidality and positive psychological constructs at 6 and 12 weeks were tested using mixed-effects models accounting for intensity of post-hospitalization psychiatric treatment. Compared with PP, the CF intervention was associated with significantly greater improvements in hopelessness at 6 weeks (β = -3.15, 95% confidence interval -6.18 to -0.12, effect size = -0.84, p = 0.04), but not 12 weeks. Similarly, the CF intervention led to greater improvements in depression, suicidal ideation, optimism and gratitude at 6 and 12 weeks. Contrary to our hypothesis, the CF intervention was superior to PP in improving hopelessness, other suicide risk factors and positive psychological constructs during a key post-discharge period among suicidal patients with depression. Further study of this CF intervention is warranted in populations at high suicide risk.

Psychological interventions to reduce suicidality in high-risk patients with major depression: a randomized controlled trial

PubMed Central

Celano, C. M.; Beale, E. E.; Mastromauro, C. A.; Stewart, J. G.; Millstein, R. A.; Auerbach, R. P.; Bedoya, C. A.; Huffman, J. C.

2016-01-01

Background Positive psychological constructs have been associated with reduced suicidal ideation, and interventions to cultivate positive feelings have the potential to reduce suicide risk. This study compares the efficacy of a 6-week, telephone-based positive psychology (PP) intervention against a cognition-focused (CF) control intervention among patients recently hospitalized for depression and suicidal ideation or behavior. Method A total of 65 adults with a current major depressive episode reporting suicidal ideation or a recent suicide attempt were enrolled from participating in-patient psychiatric units. Prior to discharge, participants were randomized to the PP (n = 32) or CF (n = 33) intervention. In both interventions, participants received a treatment manual, performed weekly PP (e.g. gratitude letter) or CF (e.g. recalling daily events) exercises, and completed weekly one-on-one telephone sessions over 6 weeks. Between-group differences in hopelessness (primary outcome), depression, suicidality and positive psychological constructs at 6 and 12 weeks were tested using mixed-effects models accounting for intensity of post-hospitalization psychiatric treatment. Results Compared with PP, the CF intervention was associated with significantly greater improvements in hopelessness at 6 weeks (β = −3.15, 95% confidence interval −6.18 to −0.12, effect size = −0.84, p = 0.04), but not 12 weeks. Similarly, the CF intervention led to greater improvements in depression, suicidal ideation, optimism and gratitude at 6 and 12 weeks. Conclusions Contrary to our hypothesis, the CF intervention was superior to PP in improving hopelessness, other suicide risk factors and positive psychological constructs during a key post-discharge period among suicidal patients with depression. Further study of this CF intervention is warranted in populations at high suicide risk. PMID:27876105

Is sweat chloride predictive of severity of cystic fibrosis lung disease assessed by chest computed tomography?

PubMed

Caudri, Daan; Zitter, David; Bronsveld, Inez; Tiddens, Harm

2017-09-01

Cystic Fibrosis (CF) lung disease is characterized by a marked heterogeneity. Sweat chloride-level is a functional marker of the CF Transmembrane Regulator (CFTR) protein and could be an important predictor of later disease severity. In this retrospective analysis children from the Rotterdam CF clinic with available sweat chloride level at diagnosis and at least one routine spirometry-controlled volumetric chest CT scan in follow-up were included. CT scans were scored using the CF-CT scoring system (% of maximum). Associations between sweat chloride-levels and CF-CT scores were calculated using linear regression models, adjusting for age at sweat test and age at follow-up. Because structural lung damage develops over the course of many years, effect modification by the age at follow-up CT-scan was tested for by age-stratification. In 59 children (30 male) sweat chloride was measured at diagnosis (median age 0.5 years, range 0-13) and later chest CT performed (median age 14 years, range 6-18). Sweat chloride was associated with significantly higher CT-CT total score, bronchiectasis score, and mucus plugging score. Stratification for age at follow-up in tertiles showed this association remained only in the oldest age group (range 15-18 years). In that subgroup associations were found with all but one of the CF-CT subscores, as well as with all tested lung functions parameters. Sweat chloride-level is a significant predictor of CF lung disease severity as determined by chest CT and lung function. This association could only be demonstrated in children with follow-up to age 15 years and above. © 2017 Wiley Periodicals, Inc.

Influence of SNPs in Genes that Modulate Lung Disease Severity in a Group of Mexican Patients with Cystic Fibrosis.

PubMed

Yokoyama, Emiy; Chávez-Saldaña, Margarita; Orozco, Lorena; Cuevas, Francisco; Lezana, José Luis; Vigueras-Villaseñor, Rosa María; Rojas-Castañeda, Julio Cesar; Landero, Daniel Adrian

2018-04-24

The variation in cystic fibrosis (CF) lung disease not always is explained by the CFTR genotype, so it has become apparent that modifier genes must play a considerable role in the phenotypic heterogeneity of CF, so we investigated the association of allelic variants in modifier genes that modulate the severity of lung function in a group of Mexican patients diagnosed with CF. We included 140 CF patients classified according to lung phenotype and analyzed 17 single nucleotide polymorphisms (SNPs) by TaqMan ® allelic discrimination. We demonstrated that patients with GG or GC genotype of the allelic variant rs11003125 (MBL2-550) of the MBL2 gene exhibit most of the lung manifestations at an earlier age; and the rs1042713 allelic variant of ADRB2 gene, showed statistical difference only with the age of first spirometry. When we used the dominant model, the MBL2 allele rs11003125 (MBL2-550; p = 0.022, Odds Ratio (OR) 2.87, 95% CI 1.14-7.27) was significantly associated with CF patients as risk factor, and the ADRB2 allele rs1042713 (p.Arg16Gly; p = 0.005, Odds Ratio (OR) 0.37, 95% CI 0.19-0.75) was significantly associated with CF patients as protect factor. Our findings suggest that the MBL2 and ADRB2 genes exerts an important genetic influence on the lung disease in our patients. Taking into account our results, we insist on not leaving aside this type of studies, since having techniques such as GWAS or WES will be able to advance in achieving a better quality of life for CF patients with severe lung disease. Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.

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.

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.

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

Attitudes and Decision Making Related to Pregnancy Among Young Women with Cystic Fibrosis.

PubMed

Kazmerski, Traci M; Gmelin, Theresa; Slocum, Breonna; Borrero, Sonya; Miller, Elizabeth

2017-04-01

Introduction The number of female patients with CF able to consider pregnancy has increased with improved therapies. This study explored attitudes and decision making regarding pregnancy among young women with CF. Methods Twenty-two women with CF ages 18-30 years completed semi-structured, in-person interviews exploring experiences with preconception counseling and reproductive care in the CF setting. Interviews were audio-recorded, transcribed, and coded using a thematic analysis approach. Results Participants indicated CF is a major factor in pregnancy decision making. Although women acknowledged that CF influences attitudes toward pregnancy, many expressed confusion about how CF can affect fertility/pregnancy. Many perceived disapproval from CF providers regarding pregnancy and were dissatisfied with reproductive care in the CF setting. Discussion Young female patients with CF reported poor understanding of the effect of CF on fertility and pregnancy and limited preconception counseling in CF care. Improvements in female sexual and reproductive health care in CF are warranted.

Quantum Theory of Atoms in Molecules Charge-Charge Transfer-Dipolar Polarization Classification of Infrared Intensities.

PubMed

Duarte, Leonardo J; Richter, Wagner E; Silva, Arnaldo F; Bruns, Roy E

2017-10-26

Fundamental infrared vibrational transition intensities of gas-phase molecules are sensitive probes of changes in electronic structure accompanying small molecular distortions. Models containing charge, charge transfer, and dipolar polarization effects are necessary for a successful classification of the C-H, C-F, and C-Cl stretching and bending intensities. C-H stretching and in-plane bending vibrations involving sp 3 carbon atoms have small equilibrium charge contributions and are accurately modeled by the charge transfer-counterpolarization contribution and its interaction with equilibrium charge movement. Large C-F and C═O stretching intensities have dominant equilibrium charge movement contributions compared to their charge transfer-dipolar polarization ones and are accurately estimated by equilibrium charge and the interaction contribution. The C-F and C-Cl bending modes have charge and charge transfer-dipolar polarization contribution sums that are of similar size but opposite sign to their interaction values resulting in small intensities. Experimental in-plane C-H bends have small average intensities of 12.6 ± 10.4 km mol -1 owing to negligible charge contributions and charge transfer-counterpolarization cancellations, whereas their average out-of-plane experimental intensities are much larger, 65.7 ± 20.0 km mol -1 , as charge transfer is zero and only dipolar polarization takes place. The C-F bending intensities have large charge contributions but very small intensities. Their average experimental out-of-plane intensity of 9.9 ± 12.6 km mol -1 arises from the cancellation of large charge contributions by dipolar polarization contributions. The experimental average in-plane C-F bending intensity, 5.8 ± 7.3 km mol -1 , is also small owing to charge and charge transfer-counterpolarization sums being canceled by their interaction contributions. Models containing only atomic charges and their fluxes are incapable of describing electronic structure changes for simple molecular distortions that are of interest in classifying infrared intensities. One can expect dipolar polarization effects to also be important for larger distortions of chemical interest.

Crosslinking and degradation mechanisms in model sealant candidates

NASA Technical Reports Server (NTRS)

Paciorek, K. L.; Kaufman, J.; Kratzer, R. H.

1974-01-01

Heterocyclic ring systems were investigated, triazines and 1,2,4-oxadiazoles. Only a limited effort was extended to the preparation of triazoles. Compounds, n-perfluoroheptyl-s-triazine, a perfluoroether substituted triazine, C3F7OCF(CF3)CF2OCF(CF3) 3C3N3,1,4-bus (5-perfluoro-n-heptyl)-1,2,4-oxadiazolyl -benzene, its perfluoroalkylether substituded analogue, and 3,5-bis(perfluoro-n-heptyl)-1,2,4-oxadiazole were synthesized and characterized. To eliminate the effect due to a tertiary fluorine present in branched materials, the pure n-alkyl-compounds were prepared. The main starting material, perfluoro-n-octanonitrile, was obtained from commercially available perfluoro-n-octanoic acid via a three step synthesis.

Clairvoyant fusion: a new methodology for designing robust detection algorithms

NASA Astrophysics Data System (ADS)

Schaum, Alan

2016-10-01

Many realistic detection problems cannot be solved with simple statistical tests for known alternative probability models. Uncontrollable environmental conditions, imperfect sensors, and other uncertainties transform simple detection problems with likelihood ratio solutions into composite hypothesis (CH) testing problems. Recently many multi- and hyperspectral sensing CH problems have been addressed with a new approach. Clairvoyant fusion (CF) integrates the optimal detectors ("clairvoyants") associated with every unspecified value of the parameters appearing in a detection model. For problems with discrete parameter values, logical rules emerge for combining the decisions of the associated clairvoyants. For many problems with continuous parameters, analytic methods of CF have been found that produce closed-form solutions-or approximations for intractable problems. Here the principals of CF are reviewed and mathematical insights are described that have proven useful in the derivation of solutions. It is also shown how a second-stage fusion procedure can be used to create theoretically superior detection algorithms for ALL discrete parameter problems.

Brush border membrane vesicle and Caco-2 cell line: Two experimental models for evaluation of absorption enhancing effects of saponins, bile salts, and some synthetic surfactants

PubMed Central

Moghimipour, Eskandar; Tabassi, Sayyed Abolghassem Sajadi; Ramezani, Mohammad; Handali, Somayeh; Löbenberg, Raimar

2016-01-01

The aim of this study was to investigate the influence of absorption enhancers in the uptake of hydrophilic compounds. The permeation of the two hydrophilic drug models gentamicin and 5 (6)-carboxyfluorescein (CF) across the brush border membrane vesicles and Caco-2 cell lines were evaluated using total saponins of Acanthophyllum squarrosum, Quillaja saponaria, sodium lauryl sulfate, sodium glycocholate, sodium taurodeoxycholate, and Tween 20 as absorption enhancers. Transepithelial electrical resistance (TEER) measurement was utilized to assess the paracellular permeability of cell lines. Confocal laser scanning microscopy (CLSM) was performed to obtain images of the distribution of CF in Caco-2 cells. These compounds were able to loosen tight junctions, thus increasing paracellular permeability. CLSM confirmed the effect of these absorption enhancers on CF transport across Caco-2 lines and increased the Caco-2 permeability via transcellular route. It was also confirmed that the decrease in TEER was transient and reversible after removal of permeation enhancers. PMID:27429925

Fusion and elastic scattering of 6Li + 58Ni at low energies

NASA Astrophysics Data System (ADS)

Aguilera, Elí F.; Amador-Valenzuela, Paulina; Martinez-Quiroz, Enrique; Lizcano, David; Garcia-Flores, Araceli; Kolata, James J.

2017-11-01

Sub-barrier fusion cross sections (σfus) for the 6Li + 58Ni system, obtained from the respective evaporation protons, are examined in the present work. With respect to expectations of a simple one-dimensional barrier penetration model, a large enhancement of the data is observed. Good consistency with equivalent data reported previously for similar systems is found. A comparison with total reaction cross sections (σR), deduced from elastic scattering measurements reported previously, indicates that σfus is close to σR within the measured energy range. To estimate the contribution of complete fusion (CF), an optical model analysis of the elastic scattering data is performed where CF is identified with the absorption in a short range volume potential. A surface polarization potential is added to the bare nuclear potential to simulate the effect of peripheral reactions. The results obtained indicate that other mechanisms different from CF may be dominant, especially in the lower energy region.

Impact of bronchiectasis and trapped air on quality of life and exacerbations in cystic fibrosis.

PubMed

Tepper, Leonie A; Utens, Elisabeth M W J; Caudri, Daan; Bos, Aukje C; Gonzalez-Graniel, Karla; Duivenvoorden, Hugo J; van der Wiel, Els C W; Quittner, Alexandra L; Tiddens, Harm A W M

2013-08-01

Cystic fibrosis (CF) is primarily characterised by bronchiectasis and trapped air on chest computed tomography (CT). The revised Cystic Fibrosis Questionnaire respiratory symptoms scale (CFQ-R RSS) measures health-related quality of life. To validate bronchiectasis, trapped air and CFQ-R RSS as outcome measures, we investigated correlations and predictive values for pulmonary exacerbations. CF patients (aged 6-20 years) underwent CT, CFQ-R RSS and 1-year follow-up. Bronchiectasis and trapped air were scored using the CF-CT scoring system. Correlation coefficients and backward multivariate modelling were used to identify predictors of pulmonary exacerbations. 40 children and 32 adolescents were included. CF-CT bronchiectasis (r = -0.38, p<0.001) and CF-CT trapped air (r = -0.35, p = 0.003) correlated with CFQ-R RSS. Pulmonary exacerbations were associated with: bronchiectasis (rate ratio 1.10, 95% CI 1.02-1.19; p = 0.009), trapped air (rate ratio 1.02, 95% CI 1.00-1.05; p = 0.034) and CFQ-R RSS (rate ratio 0.95, 95% CI 0.91-0.98; p = 0.002). The CFQ-R RSS was an independent predictor of pulmonary exacerbations (rate ratio 0.96, 95% CI 0.94-0.97; p<0.001). Bronchiectasis, trapped air and CFQ-R RSS were associated with pulmonary exacerbations. The CFQ-R RSS was an independent predictor. This study further validated bronchiectasis, trapped air and CFQ-R RSS as outcome measures in CF.

Molecular relaxation processes in dimethyldichlorosilane studied by vibrational spectroscopy

NASA Astrophysics Data System (ADS)

Bratu, I.; Grecu, Rodica; Iliescu, T.

1995-04-01

The paper presents the experimentally determined correlation functions ( CF) of the bands due to IR and Raman active vibrations ν asSiCl 2 and ν sSiCl 2 of dimethyldichlorosilane ( DMDCS) in pure liquid and in solutions. Both reorientational and vibrational relaxations (the last one being dominant) contribute to the profiles of these vibrational modes. Kubo-Rothschild's and Oxtoby's models compared with the experimental CF indicate an intermediate modulation regime.

Regions of the Cf-9B disease resistance protein able to cause spontaneous necrosis in Nicotiana benthamiana lie within the region controlling pathogen recognition in tomato.

PubMed

Chakrabarti, Apratim; Panter, Stephen N; Harrison, Kate; Jones, Jonathan D G; Jones, David A

2009-10-01

The tomato Cf-9 and Cf-9B genes both confer resistance to the leaf mold fungus Cladosporium fulvum but only Cf-9 confers seedling resistance and recognizes the avirulence (Avr) protein Avr9 produced by C. fulvum. Using domain swaps, leucine-rich repeats (LRR) 5 to 15 of Cf-9 were shown to be required for Cf-9-specific resistance to C. fulvum in tomato, and the entire N-terminus up to LRR15 of Cf-9B was shown to be required for Cf-9B-specific resistance. Finer domain swaps showed that nine amino-acid differences in LRR 13 to 15 provided sufficient Cf-9-specific residues in a Cf-9B context for recognition of Avr9 in Nicotiana tabacum or sufficient Cf-9B residues in a Cf-9 context for a novel necrotic response caused by the expression of Cf-9B in N. benthamiana. The responses conferred by LRR 13 to 15 were enhanced by addition of LRR 10 to 12, and either region of Cf-9B was found to cause necrosis in N. benthamiana when the other was replaced by Cf-9 sequence in a Cf-9B context. As a consequence, the domain swap with LRR 13 to 15 of Cf-9 in a Cf-9B context gained the dual ability to recognize Avr9 and cause necrosis in N. benthamiana. Intriguingly, two Cf-9B-specific domain swaps gave differing results for necrosis assays in N. benthamiana compared with disease resistance assays in transgenic tomato. The different domain requirements in these two cases suggest that the two assays detect unrelated ligands or detect related ligands in slightly different ways. A heat-sensitive necrosis-inducing factor present in N. benthamiana intercellular washing fluids was found to cause a necrotic response in N. tabacum plants carrying Hcr9-9A, Cf-9B, and Cf-9 but not in plants carrying only Cf-9. We postulate that this necrosis-inducing factor is recognized by Cf-9B either directly as a ligand or indirectly as a regulator of Cf-9B autoactivity.

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.

Finding mouse models of human lymphomas and leukemia's using the Jackson laboratory mouse tumor biology database.

PubMed

Begley, Dale A; Sundberg, John P; Krupke, Debra M; Neuhauser, Steven B; Bult, Carol J; Eppig, Janan T; Morse, Herbert C; Ward, Jerrold M

2015-12-01

Many mouse models have been created to study hematopoietic cancer types. There are over thirty hematopoietic tumor types and subtypes, both human and mouse, with various origins, characteristics and clinical prognoses. Determining the specific type of hematopoietic lesion produced in a mouse model and identifying mouse models that correspond to the human subtypes of these lesions has been a continuing challenge for the scientific community. The Mouse Tumor Biology Database (MTB; http://tumor.informatics.jax.org) is designed to facilitate use of mouse models of human cancer by providing detailed histopathologic and molecular information on lymphoma subtypes, including expertly annotated, on line, whole slide scans, and providing a repository for storing information on and querying these data for specific lymphoma models. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Statistical characteristics of climbing fiber spikes necessary for efficient cerebellar learning.

PubMed

Kuroda, S; Yamamoto, K; Miyamoto, H; Doya, K; Kawat, M

2001-03-01

Mean firing rates (MFRs), with analogue values, have thus far been used as information carriers of neurons in most brain theories of learning. However, the neurons transmit the signal by spikes, which are discrete events. The climbing fibers (CFs), which are known to be essential for cerebellar motor learning, fire at the ultra-low firing rates (around 1 Hz), and it is not yet understood theoretically how high-frequency information can be conveyed and how learning of smooth and fast movements can be achieved. Here we address whether cerebellar learning can be achieved by CF spikes instead of conventional MFR in an eye movement task, such as the ocular following response (OFR), and an arm movement task. There are two major afferents into cerebellar Purkinje cells: parallel fiber (PF) and CF, and the synaptic weights between PFs and Purkinje cells have been shown to be modulated by the stimulation of both types of fiber. The modulation of the synaptic weights is regulated by the cerebellar synaptic plasticity. In this study we simulated cerebellar learning using CF signals as spikes instead of conventional MFR. To generate the spikes we used the following four spike generation models: (1) a Poisson model in which the spike interval probability follows a Poisson distribution, (2) a gamma model in which the spike interval probability follows the gamma distribution, (3) a max model in which a spike is generated when a synaptic input reaches maximum, and (4) a threshold model in which a spike is generated when the input crosses a certain small threshold. We found that, in an OFR task with a constant visual velocity, learning was successful with stochastic models, such as Poisson and gamma models, but not in the deterministic models, such as max and threshold models. In an OFR with a stepwise velocity change and an arm movement task, learning could be achieved only in the Poisson model. In addition, for efficient cerebellar learning, the distribution of CF spike-occurrence time after stimulus onset must capture at least the first, second and third moments of the temporal distribution of error signals.

Mouse models rarely mimic the transcriptome of human neurodegenerative diseases: A systematic bioinformatics-based critique of preclinical models.

PubMed

Burns, Terry C; Li, Matthew D; Mehta, Swapnil; Awad, Ahmed J; Morgan, Alexander A

2015-07-15

Translational research for neurodegenerative disease depends intimately upon animal models. Unfortunately, promising therapies developed using mouse models mostly fail in clinical trials, highlighting uncertainty about how well mouse models mimic human neurodegenerative disease at the molecular level. We compared the transcriptional signature of neurodegeneration in mouse models of Alzheimer׳s disease (AD), Parkinson׳s disease (PD), Huntington׳s disease (HD) and amyotrophic lateral sclerosis (ALS) to human disease. In contrast to aging, which demonstrated a conserved transcriptome between humans and mice, only 3 of 19 animal models showed significant enrichment for gene sets comprising the most dysregulated up- and down-regulated human genes. Spearman׳s correlation analysis revealed even healthy human aging to be more closely related to human neurodegeneration than any mouse model of AD, PD, ALS or HD. Remarkably, mouse models frequently upregulated stress response genes that were consistently downregulated in human diseases. Among potential alternate models of neurodegeneration, mouse prion disease outperformed all other disease-specific models. Even among the best available animal models, conserved differences between mouse and human transcriptomes were found across multiple animal model versus human disease comparisons, surprisingly, even including aging. Relative to mouse models, mouse disease signatures demonstrated consistent trends toward preserved mitochondrial function protein catabolism, DNA repair responses, and chromatin maintenance. These findings suggest a more complex and multifactorial pathophysiology in human neurodegeneration than is captured through standard animal models, and suggest that even among conserved physiological processes such as aging, mice are less prone to exhibit neurodegeneration-like changes. This work may help explain the poor track record of mouse-based translational therapies for neurodegeneration and provides a path forward to critically evaluate and improve animal models of human disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Experimental and Estimated Rate Constants for the Reactions of Hydroxyl Radicals with Several Halocarbons

NASA Technical Reports Server (NTRS)

DeMore, W.B.

1996-01-01

Relative rate experiments are used to measure rate constants and temperature dependencies of the reactions of OH with CH3F (41), CH2FCl (31), CH2BrCl (30B1), CH2Br2 (3OB2), CHBr3 (2OB3), CF2BrCHFCl (123aBl(alpha)), and CF2ClCHCl2 (122). Rate constants for additional compounds of these types are estimated using an empirical rate constant estimation method which is based on measured rate constants for a wide range of halocarbons. The experimental data are combined with the estimated and previously reported rate constants to illustrate the effects of F, Cl, and Br substitution on OH rate constants for a series of 19 halomethanes and 25 haloethanes. Application of the estimation technique is further illustrated for some higher hydrofluorocarbons (HFCs), including CHF2CF2CF2CF2H (338pcc), CF3CHFCHFCF2CF3 (43-10mee), CF3CH2CH2CF3 (356ffa), CF3CH2CF2CH2CF3 (458mfcf), CF3CH2CHF2 (245fa), and CF3CH2CF2CH3 (365mfc). The predictions are compared with literature data for these compounds.

Effect of echolocation behavior-related constant frequency-frequency modulation sound on the frequency tuning of inferior collicular neurons in Hipposideros armiger.

PubMed

Tang, Jia; Fu, Zi-Ying; Wei, Chen-Xue; Chen, Qi-Cai

2015-08-01

In constant frequency-frequency modulation (CF-FM) bats, the CF-FM echolocation signals include both CF and FM components, yet the role of such complex acoustic signals in frequency resolution by bats remains unknown. Using CF and CF-FM echolocation signals as acoustic stimuli, the responses of inferior collicular (IC) neurons of Hipposideros armiger were obtained by extracellular recordings. We tested the effect of preceding CF or CF-FM sounds on the shape of the frequency tuning curves (FTCs) of IC neurons. Results showed that both CF-FM and CF sounds reduced the number of FTCs with tailed lower-frequency-side of IC neurons. However, more IC neurons experienced such conversion after adding CF-FM sound compared with CF sound. We also found that the Q 20 value of the FTC of IC neurons experienced the largest increase with the addition of CF-FM sound. Moreover, only CF-FM sound could cause an increase in the slope of the neurons' FTCs, and such increase occurred mainly in the lower-frequency edge. These results suggested that CF-FM sound could increase the accuracy of frequency analysis of echo and cut-off low-frequency elements from the habitat of bats more than CF sound.

Coupling life-cycle assessment and the RothC model to estimate the carbon footprint of green manure-based wheat production in China.

PubMed

Yao, Zhiyuan; Zhang, Dabin; Yao, Pengwei; Zhao, Na; Liu, Na; Zhai, Bingnian; Zhang, Suiqi; Li, Yangyang; Huang, Donglin; Cao, Weidong; Gao, Yajun

2017-12-31

Reducing the carbon footprint (CF) of crop production is an efficient way to mitigate climate change. Growing legume green manure (LGM) instead of summer fallow may achieve this goal by lowering synthetic nitrogen (N) fertilizer needs and replenishing the depleted soil carbon (C) pool. The Rothamsted Carbon (RothC) model was incorporated into the Life-Cycle Assessment (LCA) to evaluate the present and projected CFs of green manure-based wheat production systems in dryland agriculture on the Loess Plateau of China. The field study included four main treatments (Huai bean, soybean and mung bean grown as green manure in summer and fallow as control) and four synthetic N rates (0, 108, 135 and 162kgNha -1 ) applied at wheat sowing. Soybean as LGM increased averaged wheat yield over 4 synthetic N rates by 8% compared with fallow (P<0.05), and synthetic N requirement was reduced by 33% without compromising the wheat yield for all the main treatments. Although LGM treatments had higher greenhouse gas (GHG) emissions from agricultural inputs, the greater amount of C inputs elevated the corresponding SOC stocks (SOCS) by 14-24% after 8years, thus significantly reducing the CF by 25-51% compared with fallow. The modelled SOCS equilibrium indicates that the CF for cropping systems with LGM will be 53-62% lower than fallow and 23-37% lower compared with their current level. In conclusion, introducing legume green manure instead of summer fallow is a highly efficient measure for persistent CF reduction, and coupling the RothC model and LCA is an alternative method to predict the long-term impact of different cropping systems on GHG emissions. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Trends in the use of mechanical circulatory support as a bridge to heart transplantation across different age groups.

PubMed

Ciarka, Agnieszka; Edwards, Leah; Nilsson, Johan; Stehlik, Josef; Lund, Lars H

2017-03-15

Numerous cohort analyses suggest rapidly increasing use of mechanical circulatory support (MCS) as a bridge to heart transplantation (HTx), but the role of age in selection for MCS remains unknown. We assessed adult HTx in the International Society for Heart And Lung Transplantation Registry between 2005 and 2013 and we determined MCS use by recipient age group and transplant year. Multivariable logistic regression models were constructed to identify variables associated with continuous flow (CF) left ventricular assist device (LVAD) use within each age group. Among 16,480 HTx recipients the percentage of overall MCS use increased from 23% to 38%, 21% to 41%, and 17% to 42% in age groups 18-39 years, 40-59 years and over 60 years, respectively. This effect was mainly due to an increase in CF LVAD use and primarily in HTx recipients aged over 60. In multivariable analyses, male gender and blood group O were significantly associated with CF LVAD use in all age groups. Bridge to transplant MCS use increased dramatically between 2005 and 2013 primarily due to increased use of CF LVAD and primarily in higher ages. Pre-HTx CF LVAD use was more frequent in men and blood group O. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Energy corrective and antioxidative actions of cytoflavin during postischemic period of human dermal fibroblasts in vitro].

PubMed

Tiuriaeva, I I; Kuranova, M L; Gonchar, I V; Rozanov, Iu M

2012-01-01

The influence of metabolic drug Cytoflavin (CF) with antihypoxic and antioxidative properties on human dermal fibroblasts in a model of ischemia-reoxygenation in vitro was studied. It was revealed that the restoration of ATP synthesis in fibroblasts in the postischemic period was considerably accelerated (in 2.1 times) by the addition of CF to the culture medium. The drug had a cell protective effect of reducing cell mortality during the reoxygenation after ischemia by 2-2.7 times. CF effectively reduced the level of reactive oxygen species (ROS) in fibroblasts after H2O2 treatment which allowed maintaining their survival at the level of control cells. Pretreatment of the cells with CF for one day ensured the maintenance of normal levels of ROS during the investigated time period in the fibroblasts subjected to H2O2 treatment, and reduced H2O2-induced cell death by almost a third compared to control cells. The introduction of CF in culture medium after ischemia showed no influence on Hsp70 synthesis, but led to decrease in GRP78 synthesis, raised after ischemia, to the control level, indicating a resolve of the endoplasmic reticulum (ER) stress and functional normalization of ER.

Incorporating thyroid markers in Down syndrome screening protocols.

PubMed

Dhaifalah, Ishraq; Salek, Tomas; Langova, Dagmar; Cuckle, Howard

2017-05-01

The article aimed to assess the benefit of incorporating maternal serum thyroid disease marker levels (thyroid-stimulating hormone and free thyroxine) into first trimester Down syndrome screening protocols. Statistical modelling was used to predict performance with and without the thyroid markers. Two protocols were considered: the combined test and the contingent cell-free DNA (cfDNA) test, where 15-40% women are selected for cfDNA because of increased risk based on combined test results. Published parameters were used for the combined test, cfDNA and the Down syndrome means for thyroid-stimulating hormone and free thyroxine; other parameters were derived from a series of 5230 women screened for both thyroid disease and Down syndrome. Combined test: For a fixed 85% detection rate, the predicted false positive rate was reduced from 5.3% to 3.6% with the addition of the thyroid markers. Contingent cfDNA test: For a fixed 95% detection rate, the proportion of women selected for cfDNA was reduced from 25.6% to 20.2%. When screening simultaneously for maternal thyroid disease and Down syndrome, thyroid marker levels should be used in the calculation of Down syndrome risk. The benefit is modest but can be achieved with no additional cost. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

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.

Characterizing and Modeling the Cost of Rework in a Library of Reusable Software Components

NASA Technical Reports Server (NTRS)

Basili, Victor R.; Condon, Steven E.; ElEmam, Khaled; Hendrick, Robert B.; Melo, Walcelio

1997-01-01

In this paper we characterize and model the cost of rework in a Component Factory (CF) organization. A CF is responsible for developing and packaging reusable software components. Data was collected on corrective maintenance activities for the Generalized Support Software reuse asset library located at the Flight Dynamics Division of NASA's GSFC. We then constructed a predictive model of the cost of rework using the C4.5 system for generating a logical classification model. The predictor variables for the model are measures of internal software product attributes. The model demonstrates good prediction accuracy, and can be used by managers to allocate resources for corrective maintenance activities. Furthermore, we used the model to generate proscriptive coding guidelines to improve programming, practices so that the cost of rework can be reduced in the future. The general approach we have used is applicable to other environments.

Cable Pili and the Associated 22 Kda Adhesin Contribute to Burkholderia Cenocepacia Persistence In Vivo

PubMed Central

Goldberg, Joanna B.; Ganesan, Shyamala; Comstock, Adam T.; Zhao, Ying; Sajjan, Uma S.

2011-01-01

Background Infection by Burkholderia cenocepacia in cystic fibrosis (CF) patients is associated with poor clinical prognosis. Previously, we demonstrated that one of the highly transmissible strains, BC7, expresses cable pili and the associated 22 kDa adhesin, both of which contribute to BC7 binding to airway epithelial cells. However, the contribution of these factors to induce inflammation and bacterial persistence in vivo is not known. Methodology/Principal Findings Wild-type BC7 stimulated higher IL-8 responses than the BC7 cbl and BC7 adhA mutants in both CF and normal bronchial epithelial cells. To determine the role of cable pili and the associated adhesin, we characterized a mouse model of B. cenocepacia, where BC7 are suspended in Pseudomonas aeruginosa alginate. C57BL/6 mice were infected intratracheally with wild-type BC7 suspended in either alginate or PBS and were monitored for lung bacterial load and inflammation. Mice infected with BC7 suspended in PBS completely cleared the bacteria by 3 days and resolved the inflammation. In contrast, mice infected with BC7 suspended in alginate showed persistence of bacteria and moderate lung inflammation up to 5 days post-infection. Using this model, mice infected with the BC7 cbl and BC7 adhA mutants showed lower bacterial loads and mild inflammation compared to mice infected with wild-type BC7. Complementation of the BC7 cblS mutation in trans restored the capacity of this strain to persist in vivo. Immunolocalization of bacteria revealed wild-type BC7 in both airway lumen and alveoli, while the BC7 cbl and BC7 adhA mutants were found mainly in airway lumen and peribronchiolar region. Conclusions and Significance B. cenocepacia suspended in alginate can be used to determine the capacity of bacteria to persist and cause lung inflammation in normal mice. Both cable pili and adhesin contribute to BC7-stimulated IL-8 response in vitro, and BC7 persistence and resultant inflammation in vivo. PMID:21811611

Theoretical studies on atmospheric chemistry of HFE-245mc and perfluoro-ethyl formate: Reaction with OH radicals, atmospheric fate of alkoxy radical and global warming potential

NASA Astrophysics Data System (ADS)

Lily, Makroni; Baidya, Bidisha; Chandra, Asit K.

2017-02-01

Theoretical studies have been performed on the kinetics, mechanism and thermochemistry of the hydrogen abstraction reactions of CF3CF2OCH3 (HFE-245mc) and CF3CF2OCHO with OH radical using DFT based M06-2X method. IRC calculation shows that both hydrogen abstraction reactions proceed via weakly bound hydrogen-bonded complex preceding to the formation of transition state. The rate coefficients calculated by canonical transition state theory along with Eckart's tunnelling correction at 298 K: k1(CF3CF2OCH3 + OH) = 1.09 × 10-14 and k2(CF3CF2OCHO + OH) = 1.03 × 10-14 cm3 molecule-1 s-1 are in very good agreement with the experimental values. The atmospheric implications of CF3CF2OCH3 and CF3CF2OCHO are also discussed.

Ambulatory Aortic Stiffness Is Associated With Narrow Retinal Arteriolar Caliber in Hypertensives: The SAFAR Study.

PubMed

Aissopou, Evaggelia K; Argyris, Antoniοs A; Nasothimiou, Efthimia G; Konstantonis, George D; Tampakis, Kostas; Tentolouris, Nikolaos; Papathanassiou, Miltiadis; Theodossiadis, Panagiotis G; Papaioannou, Theodoros G; Stehouwer, Coen D A; Sfikakis, Petros P; Protogerou, Athanassios D

2016-05-01

Arterial stiffness measured under static conditions reclassifies significantly cardiovascular (CV) risk and associates with narrower retinal arterioles. However, arterial stiffness exhibits circadian variation, thus single static stiffness recordings do not correspond to the "usual" 24 hr, awake, and asleep average arterial stiffness. We aimed to test the hypothesis that ambulatory 24 hr, awake, and asleep aortic (a) pulse wave velocity (PWV) associate with retinal vessel calibers, independently of confounders and of static arterial stiffness, in hypertensive individuals free from diabetes and CV disease. Digital retinal images were obtained (181 individuals, age: 53.9±10.7 years, 55.2% men) and retinal vessel calibers were measured with validated software to determine central retinal arteriolar and venular equivalents (CRAE and CRVE, respectively); ambulatory (24 hr, awake, asleep) and static office aPWV were estimated by Mobil-O-Graph; and static office carotid to femoral (cf) PWV by SphygmoCor. Regression analysis performed in 320 gradable retinal images showed that, after adjustment for confounders: (i) ambulatory aPWV was significantly associated with narrower retinal arterioles but not with venules; (ii) asleep aPWV had stronger associations with CRAE than awake aPWV; (iii) both ambulatory aPWV and cfPWV were associated mutually independently with narrower retinal arterioles; aPWV introduction in the model of cfPWV, improved model's R2 (P = 0.012). Similar discriminatory ability of 24 hr aPWV and of cfPWV to detect the presence of retinal arteriolar narrowing was found. Ambulatory aPWV, estimated by an operator-independent method, provides additional information to cfPWV regarding the associations of arterial stiffness with the retinal vessel calibers. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neonatal Injury at Cephalic Vaginal Delivery: A Retrospective Analysis of Extent of Association with Shoulder Dystocia

PubMed Central

Iskender, Cantekin; Kaymak, Oktay; Erkenekli, Kudret; Ustunyurt, Emin; Uygur, Dilek; Yakut, Halil Ibrahim; Danisman, Nuri

2014-01-01

Purpose To describe the risk factors and labor characteristics of Clavicular fracture (CF) and brachial plexus injury (BPI); and compare antenatal and labor characteristics and prognosis of obstetrical BPI associated with shoulder dystocia with obstetrical BPI not associated with shoulder dystocia. Methods This retrospective study consisted of women who gave birth to an infant with a fractured clavicle or BPI between January 2009 and June 2013. Antenatal and neonatal data were compared between groups. The control group (1300) was composed of the four singleton vaginal deliveries that immediately followed each birth injury. A multivariable logistic regression model, with backward elimination, was constructed in order to find independent risk factors associated with BPI and CF. A subgroup analysis involved comparison of features of BPI cases with or without associated shoulder dystocia. Results During the study period, the total number of vaginal deliveries was 44092. The rates of CF, BPI and shoulder dystocia during the study period were 0,6%, 0,16% and 0,29%, respectively. In the logistic regression model, shoulder dystocia, GDM, multiparity, gestational age >42 weeks, protracted labor, short second stage of labor and fetal birth weight greater than 4250 grams increased the risk of CF independently. Shoulder dystocia and protracted labor were independently associated with BPI when controlled for other factors. Among neonates with BPI whose injury was not associated with shoulder dystocia, five (12.2%) sustained permanent injury, whereas one neonate (4.5%) with BPI following shoulder dystocia sustained permanent injury (p = 0.34). Conclusion BPI not associated with shoulder dystocia might have a higher rate of concomitant CF and permanent sequelae. PMID:25144234

Differential In Vitro and In Vivo Toxicities of Antimicrobial Peptide Prodrugs for Potential Use in Cystic Fibrosis

PubMed Central

Schütte, André; Reeves, Emer; Greene, Catherine; Humphreys, Hilary; Mall, Marcus; Fitzgerald-Hughes, Deirdre; Devocelle, Marc

2016-01-01

There has been considerable interest in the use of antimicrobial peptides (AMPs) as antimicrobial agents for the treatment of many conditions, including cystic fibrosis (CF). The challenging conditions of the CF patient lung require robust AMPs that are active in an environment of high proteolytic activity but that also have low cytotoxicity and immunogenicity. Previously, we developed prodrugs of AMPs that limited the cytotoxic effects of AMP treatment by rendering the antimicrobial activity dependent on the host enzyme neutrophil elastase (NE). However, cytotoxicity remained an issue. Here, we describe the further optimization of the AMP prodrug (pro-AMP) model for CF to produce pro-WMR, a peptide with greatly reduced cytotoxicity (50% inhibitory concentration against CFBE41o- cells, >300 μM) compared to that of the previous group of pro-AMPs. The bactericidal activity of pro-WMR was increased in NE-rich bronchoalveolar lavage (BAL) fluid from CF patients (range, 8.4% ± 6.9% alone to 91.5% ± 5.8% with BAL fluid; P = 0.0004), an activity differential greater than that of previous pro-AMPs. In a murine model of lung delivery, the pro-AMP modification reduced host toxicity, with pro-WMR being less toxic than the active peptide. Previously, host toxicity issues have hampered the clinical application of AMPs. However, the development of application-specific AMPs with modifications that minimize toxicity similar to those described here can significantly advance their potential use in patients. The combination of this prodrug strategy with a highly active AMP has the potential to produce new therapeutics for the challenging conditions of the CF patient lung. PMID:26902766

Effect of Graphene Oxide Mixed Epoxy on Mechanical Properties of Carbon Fiber/Acrylonitrile-Butadiene-Styrene Composites.

PubMed

Wang, Cuicui; Ge, Heyi; Ma, Xiaolong; Liu, Zhifang; Wang, Ting; Zhang, Jingyi

2018-04-01

In this study, the watersoluble epoxy resin was prepared via the ring-opening reaction between diethanolamine and epoxy resin. The modified resin mixed with graphene oxide (GO) as a sizing agent was coated onto carbon fiber (CF) and then the GO-CF reinforced acrylonitrile-butadienestyrene (ABS) composites were prepared. The influences of the different contents of GO on CF and CF/ABS composite were explored. The combination among epoxy, GO sheets and maleic anhydride grafted ABS (ABSMA) showed a synergistic effect on improving the properties of GO-CF and GO-CF/ABS composite. The GO-CF had higher single tensile strength than the commercial CF. The maximum ILSS of GO-CF/ABS composite obtained 19.2% improvement as compared with that of the commercial CF/ABS composite. Such multiscale enhancement method and the synergistic reinforced GO-CF/ABS composite show good prospective applications in many industry areas.

[Effect of mineral N fertilizer reduction and organic fertilizer substitution on soil biological properties and aggregate characteristics in drip-irrigated cotton field.

PubMed

Li, Rui; Tai, Rui; Wang, Dan; Chu, Gui-Xin

2017-10-01

A four year field study was conducted to determine how soil biological properties and soil aggregate stability changed when organic fertilizer and biofertilizer were used to reduce chemical fertilizer application to a drip irrigated cotton field. The study consisted of six fertilization treatments: unfertilized (CK); chemical fertilizer (CF, 300 kg N·hm -2 ; 90 kg P2O5 · hm -2 , 60 kg K2 O·hm -2 ); 80% CF plus 3000 kg·hm -2 organic fertilizer (80%CF+OF); 60% CF plus 6000 kg·hm -2 organic fertilizer (60%CF+OF); 80% CF plus 3000 kg·hm -2 biofertilizer (80%CF+BF); and 60% CF plus 6000 kg·hm -2 biofertilizer (60%CF+BF). The relationships among soil organic C, soil biological properties, and soil aggregate size distribution were determined. The results showed that organic fertilizer and biofertilizer both significantly increased soil enzyme activities. Compared with CF, the biofertilizer treatments increased urease activity by 55.6%-84.0%, alkaline phosphatise activity by 53.1%-74.0%, invertase activity by 15.1%-38.0%, β-glucosidase activity by 38.2%-68.0%, polyphenoloxidase activity by 29.6%-52.0%, and arylsulfatase activity by 35.4%-58.9%. Soil enzyme activity increased as the amount of organic fertilizer and biofertilizer increased (i.e., 60%CF+OF > 80%CF+OF, 60%CF+BF > 80%CF+BF). Soil basal respiration decreased significantly in the order BF > OF > CF > CK. Soil microbial biomass C and N were 22.3% and 43.5% greater, respectively, in 60%CF+BF than in CF. The microbial biomass C:N was significantly lower in 60%CF+BF than in CF. The organic fertilizer and the biofertilizer both improved soil aggregate structure. Soil mass in the >0.25 mm fraction was 7.1% greater in 80%CF+OF and 8.0% greater in (60%CF+OF) than in CF. The geometric mean diameter was 9.2% greater in 80%CF+BF than in 80%CF+OF. Redundancy analysis and cluster analysis both demonstrated that soil aggregate structure and biological activities increased when organic fertilizer and biofertilizer were used to reduce chemical fertilizer application. In conclusion, the organic fertilizer and the biofertilizer significantly increased SOC, soil enzyme activity, and soil microbial biomass C and N. The organic fertilizers also improved soil aggregation. Therefore, soil quality could be improved by using these fertilizers to reduce chemical fertilizer application, especially under drip-irrigation.

Multi-scale quantum point contact model for filamentary conduction in resistive random access memories devices

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

Lian, Xiaojuan, E-mail: xjlian2005@gmail.com; Cartoixà, Xavier; Miranda, Enrique

2014-06-28

We depart from first-principle simulations of electron transport along paths of oxygen vacancies in HfO{sub 2} to reformulate the Quantum Point Contact (QPC) model in terms of a bundle of such vacancy paths. By doing this, the number of model parameters is reduced and a much clearer link between the microscopic structure of the conductive filament (CF) and its electrical properties can be provided. The new multi-scale QPC model is applied to two different HfO{sub 2}-based devices operated in the unipolar and bipolar resistive switching (RS) modes. Extraction of the QPC model parameters from a statistically significant number of CFsmore » allows revealing significant structural differences in the CF of these two types of devices and RS modes.« less

Differences in Outcomes between Early and Late Diagnosis of Cystic Fibrosis in the Newborn Screening Era.

PubMed

Coffey, Michael J; Whitaker, Viola; Gentin, Natalie; Junek, Rosie; Shalhoub, Carolyn; Nightingale, Scott; Hilton, Jodi; Wiley, Veronica; Wilcken, Bridget; Gaskin, Kevin J; Ooi, Chee Y

2017-02-01

To evaluate children with cystic fibrosis (CF) who had a late diagnosis of CF (LD-CF) despite newborn screening (NBS) and compare their clinical outcomes with children diagnosed after a positive NBS (NBS-CF). A retrospective review of patients with LD-CF in New South Wales, Australia, from 1988 to 2010 was performed. LD-CF was defined as NBS-negative (negative immunoreactive trypsinogen or no F508del) or NBS-positive but discharged following sweat chloride < 60 mmol/L. Cases of LD-CF were each matched 1:2 with patients with NBS-CF for age, sex, hospital, and exocrine pancreatic status. A total of 45 LD-CF cases were identified (39 NBS-negative and 6 NBS-positive) with 90 NBS-CF matched controls. Median age (IQR) of diagnosis for LD-CF and NBS-CF was 1.35 (0.4-2.8) and 0.12 (0.03-0.2) years, respectively (P <.0001). Estimated incidence of LD-CF was 1 in 45 000 live births. Compared with NBS-CF, LD-CF had more respiratory manifestations at time of diagnosis (66% vs 4%; P <.0001), a higher rate of hospital admission per year for respiratory illness (0.49 vs 0.2; P = .0004), worse lung function (forced expiratory volume in 1 second percentage of predicted, 0.88 vs 0.97; P = .007), and higher rates of chronic colonization with Pseudomonas aeruginosa (47% vs 24%; P = .01). The LD-CF cohort also appeared to be shorter than NBS-CF controls (mean height z-score -0.65 vs -0.03; P = .02). LD-CF, despite NBS, seems to be associated with worse health before diagnosis and worse later growth and respiratory outcomes, thus providing further support for NBS programs for CF. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Representation of Small-Arms Effects in Aggregated Force-on-Force Combat Models.

DTIC Science & Technology

1984-03-01

CONPUTATICY OF FORCE RATIO AND FRACTIONAL VALUE LOST 54 ***** 0 G. SCALING* COMPUTATION OF CASUALTIES AND WlAPCN LOSSES .. .. .. .. .. .. .. .. . .56 VI...ammo because cf its weight or his adversary with an AK-47 capable of rapid rates of accurate fire? The argument for the long- range kill capability of...LEVEL INDEPENDENT 8. IRE ALLOCATION ICT EXPLICITY CONSIDERED 9. SYMB!TRIC 10. 30 CCNSIDERXTION CF NONCOMBAT LOSSES (E.G. DESERTIONS, S URRENDERS) 11

CF6 jet engine performance improvement program. Short core exhaust nozzle performance improvement concept. [specific fuel consumption reduction

NASA Technical Reports Server (NTRS)

Fasching, W. A.

1979-01-01

The short core exhaust nozzle was evaluated in CF6-50 engine ground tests including performance, acoustic, and endurance tests. The test results verified the performance predictions from scale model tests. The short core exhaust nozzle provides an internal cruise sfc reduction of 0.9 percent without an increase in engine noise. The nozzle hardware successfully completed 1000 flight cycles of endurance testing without any signs of distress.

Advances in Collaborative Filtering

NASA Astrophysics Data System (ADS)

Koren, Yehuda; Bell, Robert

The collaborative filtering (CF) approach to recommenders has recently enjoyed much interest and progress. The fact that it played a central role within the recently completed Netflix competition has contributed to its popularity. This chapter surveys the recent progress in the field. Matrix factorization techniques, which became a first choice for implementing CF, are described together with recent innovations. We also describe several extensions that bring competitive accuracy into neighborhood methods, which used to dominate the field. The chapter demonstrates how to utilize temporal models and implicit feedback to extend models accuracy. In passing, we include detailed descriptions of some the central methods developed for tackling the challenge of the Netflix Prize competition.

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.

Towards a parameterization of convective wind gusts in Sahel

NASA Astrophysics Data System (ADS)

Largeron, Yann; Guichard, Françoise; Bouniol, Dominique; Couvreux, Fleur; Birch, Cathryn; Beucher, Florent

2014-05-01

West Africa is responsible for between 25 and 50 % of the global emissions of mineral dust (cf [Engelstaedter et al., 2006]) and these dust emissions have a huge impact on climate (cf [Carslaw et al., 2010]) and soil erosion. Numerous studies have focused on the quantification of the dust emission fluxes from knowledges of the soil surface characteristics, leading to the formulation of a threshold wind friction velocity (cf [Marticorena and Bergametti, 1995]) above which the dust can be uplifted. That flux varies with the cube of the surface wind speed above the threshold and is therefore particularly sensitive to the way the wind speed is modeled (cf [Menut, 2008]). Moreover, in the Sahelian belt, about half of the dust uplift happens during isolated events which generate violent cold pool outflows from moist deep convection, and associated high surface wind speeds. Therefore, the representation of convectively generated winds appears critical (cf [Marsham et al., 2011], [Knippertz and Todd, 2012]). The present study is motivated by these issues, and is carried out within the CAVIARS French Research National Agency (ANR) project. First, we examine the ERA interim reanalysis of the ECMWF, frequently used as an input wind field for off-line dust emission models (cf [Pierre et al., 2012]). The comparison with high-frequency local measurements shows that, not unexpectedly, the increase of the surface wind speed from deep convection is not represented in large-scale reanalysis. Therefore, following [Redelsperger et al., 2000], we propose a statistical approach to introduce a formulation of the surface wind gusts during deep convection, based on the analysis of convection-permitting high resolution simulations made with the UKMO atmospheric model (CASCADE project), the AROME operational model from Meteo-France, and the MesoNH Large Eddy Simulations model. High-frequency observations are also used to complement the analysis. However, unlike [Redelsperger et al., 2000] who focused on the wet tropical Pacific region, and linked wind gusts to convective precipitation rates alone, here, we also analyse the subgrid wind distribution during convective events, and quantify the statistical moments (variance, skewness and kurtosis) in terms of mean wind speed and convective indexes such as DCAPE. Next step of the work will be to formulate a parameterization of the cold pool convective gust from those probability density functions and analytical formulaes obtained from basic energy budget models. References : [Carslaw et al., 2010] A review of natural aerosol interactions and feedbacks within the earth system. Atmospheric Chemistry and Physics, 10(4):1701{1737. [Engelstaedter et al., 2006] North african dust emissions and transport. Earth-Science Reviews, 79(1):73{100. [Knippertz and Todd, 2012] Mineral dust aerosols over the sahara: Meteorological controls on emission and transport and implications for modeling. Reviews of Geophysics, 50(1). [Marsham et al., 2011] The importance of the representation of deep convection for modeled dust-generating winds over west africa during summer.Geophysical Research Letters, 38(16). [Marticorena and Bergametti, 1995] Modeling the atmospheric dust cycle: 1. design of a soil-derived dust emission scheme. Journal of Geophysical Research, 100(D8):16415{16. [Menut, 2008] Sensitivity of hourly saharan dust emissions to ncep and ecmwf modeled wind speed. Journal of Geophysical Research: Atmospheres (1984{2012), 113(D16). [Pierre et al., 2012] Impact of vegetation and soil moisture seasonal dynamics on dust emissions over the sahel. Journal of Geophysical Research: Atmospheres (1984{2012), 117(D6). [Redelsperger et al., 2000] A parameterization of mesoscale enhancement of surface fluxes for large-scale models. Journal of climate, 13(2):402{421.

Crystal field effect in light actinide dioxides and oxychalcogenides-a unified phenomenological description

NASA Astrophysics Data System (ADS)

Gajek, Z.

2004-05-01

The electronic properties of the actinide ions in the series of semi-conducting, antiferromagnetic compounds: dioxides, AnO2 and oxychalcogenides, AnOY, where An=U, Np and Y=S, Se, are re-examined from the point of view of the consistency of the crystal field (CF) model. The discussion is based on the supposition that the effective metal-ligand interaction solely determines the net CF effect in non-metallic compounds. The main question we address here is, whether a reliable, consistent description of the CF effect in terms of the intrinsic parameters can be achieved for this particular family of compounds. Encouraging calculations reported previously for the AnO2 and UOY series serve as a reference data in the present estimation of electronic structure parameters for neptunium oxychalcogenides.

System parameters for erythropoiesis control model: Comparison of normal values in human and mouse model

NASA Technical Reports Server (NTRS)

1979-01-01

The computer model for erythropoietic control was adapted to the mouse system by altering system parameters originally given for the human to those which more realistically represent the mouse. Parameter values were obtained from a variety of literature sources. Using the mouse model, the mouse was studied as a potential experimental model for spaceflight. Simulation studies of dehydration and hypoxia were performed. A comparison of system parameters for the mouse and human models is presented. Aside from the obvious differences expected in fluid volumes, blood flows and metabolic rates, larger differences were observed in the following: erythrocyte life span, erythropoietin half-life, and normal arterial pO2.

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.

Non-Genomic Estrogen Regulation of Ion Transport and Airway Surface Liquid Dynamics in Cystic Fibrosis Bronchial Epithelium

PubMed Central

Saint-Criq, Vinciane; Kim, Sung Hoon; Katzenellenbogen, John A.; Harvey, Brian J.

2013-01-01

Male cystic fibrosis (CF) patients survive longer than females and lung exacerbations in CF females vary during the estrous cycle. Estrogen has been reported to reduce the height of the airway surface liquid (ASL) in female CF bronchial epithelium. Here we investigated the effect of 17β-estradiol on the airway surface liquid height and ion transport in normal (NuLi-1) and CF (CuFi-1) bronchial epithelial monolayers. Live cell imaging using confocal microscopy revealed that airway surface liquid height was significantly higher in the non-CF cells compared to the CF cells. 17β-estradiol (0.1–10 nM) reduced the airway surface liquid height in non-CF and CF cells after 30 min treatment. Treatment with the nuclear-impeded Estrogen Dendrimer Conjugate mimicked the effect of free estrogen by reducing significantly the airway surface liquid height in CF and non-CF cells. Inhibition of chloride transport or basolateral potassium recycling decreased the airway surface liquid height and 17β-estradiol had no additive effect in the presence of these ion transporter inhibitors. 17β-estradiol decreased bumetanide-sensitive transepithelial short-circuit current in non-CF cells and prevented the forskolin-induced increase in ASL height. 17β-estradiol stimulated an amiloride-sensitive transepithelial current and increased ouabain-sensitive basolateral short-circuit current in CF cells. 17β-estradiol increased PKCδ activity in CF and non-CF cells. These results demonstrate that estrogen dehydrates CF and non-CF ASL, and these responses to 17β-estradiol are non-genomic rather than involving the classical nuclear estrogen receptor pathway. 17β-estradiol acts on the airway surface liquid by inhibiting cAMP-mediated chloride secretion in non-CF cells and increasing sodium absorption via the stimulation of PKCδ, ENaC and the Na+/K+ATPase in CF cells. PMID:24223826

Atmospheric Removal of Very Long-lived Greenhouse Gases in the Mesosphere

NASA Astrophysics Data System (ADS)

Totterdill, A.; Kovacs, T.; Gomez Martin, J.; FENG, W.; Chipperfield, M.; Plane, J. M.

2013-12-01

Chlorofluorocarbons are known to have serious ozone depleting and global warming potentials. Perfluorinated compounds such as SF6, NF3, SF5CF3 and CF3CF2Cl which have very long lifetimes (ranging from a few centuries to over 3000 years) are too stable to affect stratospheric ozone but do have among the highest per molecule radiative forcing of any greenhouse pollutant, making them extremely potent greenhouse gases. Due to the stability of these gases in the lower atmosphere, mesospheric loss processes could significantly reduce their estimated atmospheric lifetimes and hence, overall climate impact. Potential sinks include reactions with metals and energetic particles such as electrons or short wavelength photons already present in the upper atmosphere. The metals, in this instance iron, sodium or potassium, are produced by meteoric ablation, while background and energetic electrons have the continuous source of photoionization and auroral precipitation, respectively. In this study we investigate the removal potentials of four very long lived gases (SF6, NF3, SF5CF3 and CF3CF2Cl). First, by four metals (Fe, Mg, Na and K), where rate coefficients are measured using the Fast Flow Tube and Pulsed Laser Flash Photolysis / Laser Induced Fluorescence techniques. Second, removal by electron attachment was investigated using a quadrupole mass spectrometer. measurements. Third, Lyman-alpha (121.56 nm) photolysis was measured in a VUV absorption cell. The resulting removal rate coefficients are currently being input into the Whole Atmosphere Community Climate Model (WACCM) to obtain lifetime measurements for these species.

Adherence to airway clearance therapy in pediatric cystic fibrosis: Socioeconomic factors and respiratory outcomes.

PubMed

Oates, Gabriela R; Stepanikova, Irena; Gamble, Stephanie; Gutierrez, Hector H; Harris, William T

2015-12-01

The evidence linking socioeconomic status (SES) and adherence in cystic fibrosis (CF) is inconclusive and focused on medication uptake. We examined associations between SES, adherence to airway clearance therapy (ACT), and CF respiratory outcomes. Socioeconomic, clinical, and adherence data of CF patients (N = 110) at a single CF Center were evaluated in this cross-sectional observational study. SES was operationalized as maternal and paternal education and household income. Adherence to ACT was measured with utilization data from the high-frequency chest wall oscillation (HFCWO) device over 4-6 weeks. Statistical modeling was used to test three hypotheses: (H1) Higher SES is associated with higher ACT adherence; (H2) Higher SES is associated with better respiratory outcomes; and (H3) ACT adherence mediates the relationship between SES and respiratory outcomes. In multinomial logistic regression, maternal college education, annual income >$50,000, and more adults in the household were independently related to better adherence (P < 0.05). Paternal college education, income >$100,000, and lack of exposure to smoking were independently related to higher lung function (P < 0.05). Current adherence to ACT with HFCWO was not associated with lung function over 12 months. SES is associated both with ACT adherence and respiratory outcomes in pediatric CF patients. However, the link between SES and respiratory outcomes in this study was not mediated by adherence to ACT with HFCWO. These data emphasize the importance of socioeconomic resources and household environment for CF health. Family socio-demographic profiles can help identify patients at increased risk for ACT nonadherence. © 2015 Wiley Periodicals, Inc.

Quantitative analysis of neuronal response properties in primary and higher-order auditory cortical fields of awake house mice (Mus musculus)

PubMed Central

Joachimsthaler, Bettina; Uhlmann, Michaela; Miller, Frank; Ehret, Günter; Kurt, Simone

2014-01-01

Because of its great genetic potential, the mouse (Mus musculus) has become a popular model species for studies on hearing and sound processing along the auditory pathways. Here, we present the first comparative study on the representation of neuronal response parameters to tones in primary and higher-order auditory cortical fields of awake mice. We quantified 12 neuronal properties of tone processing in order to estimate similarities and differences of function between the fields, and to discuss how far auditory cortex (AC) function in the mouse is comparable to that in awake monkeys and cats. Extracellular recordings were made from 1400 small clusters of neurons from cortical layers III/IV in the primary fields AI (primary auditory field) and AAF (anterior auditory field), and the higher-order fields AII (second auditory field) and DP (dorsoposterior field). Field specificity was shown with regard to spontaneous activity, correlation between spontaneous and evoked activity, tone response latency, sharpness of frequency tuning, temporal response patterns (occurrence of phasic responses, phasic-tonic responses, tonic responses, and off-responses), and degree of variation between the characteristic frequency (CF) and the best frequency (BF) (CF–BF relationship). Field similarities were noted as significant correlations between CFs and BFs, V-shaped frequency tuning curves, similar minimum response thresholds and non-monotonic rate-level functions in approximately two-thirds of the neurons. Comparative and quantitative analyses showed that the measured response characteristics were, to various degrees, susceptible to influences of anesthetics. Therefore, studies of neuronal responses in the awake AC are important in order to establish adequate relationships between neuronal data and auditory perception and acoustic response behavior. PMID:24506843

Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

PubMed

Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

2015-02-01

During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

Individual calling to the feeding station can reduce agonistic interactions and lesions in group housed sows.

PubMed

Kirchner, J; Manteuffel, G; Schrader, L

2012-12-01

In this study we used a new call feeding station, which enabled sows to learn that they have access to feed only after an individual acoustic signal was given. We tested whether this call feeding station is able to reduce agonistic interactions between sows and whether effects of call feeding can further be improved by enrichment. A total of 85 gestating sows were kept in a dynamic group in a large waiting area (207 m²) equipped with littered laying areas and an outside area. During a control treatment sows were fed in a normal electronic feeding station once a day (NF1-). Before testing the call feeding station sows had been conditioned for an acoustic signal (a trisyllabic "name") and learned that they were allowed to enter the feeding station only after their name was called. In the call feeding station sows were fed either once (CF1-) or twice a day (CF2-). In addition, we tested for effects of further enrichment such as straw in the activity area (CF2+). Agonistic behaviors and number of sows were observed by video in continuous recording from 0600 to 1800 h in an area (4 by 3.25 m) in front of the feeding station in periods of 4 d (NF1- = 7 periods, CF1- = 5 periods, CF2- = 3 periods, and CF2+ = 4 periods) and analyzed using mixed models. During each observation period sows were scored for wounds and body lesions at different body parts. From 0600 to 1100 h the proportion of agonistic interactions was much greater in the feeding mode NF1- compared with CF1- (feeding mode × time of day: P < 0.001) and in CF1- agonistic interactions were on a low level throughout the whole feeding cycle. The feeding frequency and the additional presence of straw in the activity area did not affect the proportion of agonistic interactions (all P > 0.05). The results on the number of sows in front of the feeding station mirrored the findings for agonistic interactions. In NF1- more sows were involved in agonistic interactions compared with CF1- (83.1 ± 12.9% vs. 61.5 ± 19.6%; P = 0.005) but there was no difference between the call feeding station (CF) treatments. The number of severe lesions was greater at the head (P = 0.014) and the flank (P = 0.006) but not at the shoulders (P = 0.057) and the hindquarter (P = 0.426) in NF1- compared with CF1-. The results suggest that signaling the feeding time individually increases the predictability for access to the feeding station and consequently reduces competition between sows.

Ion velocities in the presheath of electronegative, radio-frequency plasmas measured by low-energy cutoff

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

Sobolewski, Mark A.; Wang, Yicheng; Goyette, Amanda

2016-07-11

Simple kinematic considerations indicate that, under certain conditions in radio-frequency (rf) plasmas, the amplitude of the low-energy peak in ion energy distributions (IEDs) measured at an electrode depends sensitively on ion velocities upstream, at the presheath/sheath boundary. By measuring this amplitude, the velocities at which ions exit the presheath can be determined and long-standing controversies regarding presheath transport can be resolved. Here, IEDs measured in rf-biased, inductively coupled plasmas in CF{sub 4} gas determined the presheath exit velocities of all significant positive ions: CF{sub 3}{sup +}, CF{sub 2}{sup +}, CF{sup +}, and F{sup +}. At higher bias voltages, we detectedmore » essentially the same velocity for all four ions. For all ions, measured velocities were significantly lower than the Bohm velocity and the electropositive ion sound speed. Neither is an accurate boundary condition for rf sheaths in electronegative gases: under certain low-frequency, high-voltage criteria defined here, either yields large errors in predicted IEDs. These results indicate that many widely used sheath models will need to be revised.« less

Atmospheric chemistry of isoflurane, desflurane, and sevoflurane: kinetics and mechanisms of reactions with chlorine atoms and OH radicals and global warming potentials.

PubMed

Sulbaek Andersen, Mads P; Nielsen, Ole J; Karpichev, Boris; Wallington, Timothy J; Sander, Stanley P

2012-06-21

The smog chamber/Fourier-transform infrared spectroscopy (FTIR) technique was used to measure the rate coefficients k(Cl + CF(3)CHClOCHF(2), isoflurane) = (4.5 ± 0.8) × 10(-15), k(Cl + CF(3)CHFOCHF(2), desflurane) = (1.0 ± 0.3) × 10(-15), k(Cl + (CF(3))(2)CHOCH(2)F, sevoflurane) = (1.1 ± 0.1) × 10(-13), and k(OH + (CF(3))(2)CHOCH(2)F) = (3.5 ± 0.7) × 10(-14) cm(3) molecule(-1) in 700 Torr of N(2)/air diluent at 295 ± 2 K. An upper limit of 6 × 10(-17) cm(3) molecule(-1) was established for k(Cl + (CF(3))(2)CHOC(O)F). The laser photolysis/laser-induced fluorescence (LP/LIF) technique was employed to determine hydroxyl radical rate coefficients as a function of temperature (241-298 K): k(OH + CF(3)CHFOCHF(2)) = (7.05 ± 1.80) × 10(-13) exp[-(1551 ± 72)/T] cm(3) molecule(-1); k(296 ± 1 K) = (3.73 ± 0.08) × 10(-15) cm(3) molecule(-1), and k(OH + (CF(3))(2)CHOCH(2)F) = (9.98 ± 3.24) × 10(-13) exp[-(969 ± 82)/T] cm(3) molecule(-1); k(298 ± 1 K) = (3.94 ± 0.30) × 10(-14) cm(3) molecule(-1). The rate coefficient of k(OH + CF(3)CHClOCHF(2), 296 ± 1 K) = (1.45 ± 0.16) × 10(-14) cm(3) molecule(-1) was also determined. Chlorine atoms react with CF(3)CHFOCHF(2) via H-abstraction to give CF(3)CFOCHF(2) and CF(3)CHFOCF(2) radicals in yields of approximately 83% and 17%. The major atmospheric fate of the CF(3)C(O)FOCHF(2) alkoxy radical is decomposition via elimination of CF(3) to give FC(O)OCHF(2) and is unaffected by the method used to generate the CF(3)C(O)FOCHF(2) radicals. CF(3)CHFOCF(2) radicals add O(2) and are converted by subsequent reactions into CF(3)CHFOCF(2)O alkoxy radicals, which decompose to give COF(2) and CF(3)CHFO radicals. In 700 Torr of air 82% of CF(3)CHFO radicals undergo C-C scission to yield HC(O)F and CF(3) radicals with the remaining 18% reacting with O(2) to give CF(3)C(O)F. Atmospheric oxidation of (CF(3))(2)CHOCH(2)F gives (CF(3))(2)CHOC(O)F in a molar yield of 93 ± 6% with CF(3)C(O)CF(3) and HCOF as minor products. The IR spectra of (CF(3))(2)CHOC(O)F and FC(O)OCHF(2) are reported for the first time. The atmospheric lifetimes of CF(3)CHClOCHF(2), CF(3)CHFOCHF(2), and (CF(3))(2)CHOCH(2)F (sevoflurane) are estimated at 3.2, 14, and 1.1 years, respectively. The 100 year time horizon global warming potentials of isoflurane, desflurane, and sevoflurane are 510, 2540, and 130, respectively. The atmospheric degradation products of these anesthetics are not of environmental concern.

Carbon nanotubes on carbon fibers: Synthesis, structures and properties

NASA Astrophysics Data System (ADS)

Zhang, Qiuhong

The interface between carbon fibers (CFs) and the resin matrix in traditional high performance composites is characterized by a large discontinuity in mechanical, electrical, and thermal properties which can cause inefficient energy transfer. Due to the exceptional properties of carbon nanotubes (CNTs), their growth at the surface of carbon fibers is a promising approach to controlling interfacial interactions and achieving the enhanced bulk properties. However, the reactive conditions used to grow carbon nanotubes also have the potential to introduce defects that can degrade the mechanical properties of the carbon fiber (CF) substrate. In this study, using thermal chemical vapor deposition (CVD) method, high density multi-wall carbon nanotubes have been successfully synthesized directly on PAN-based CF surface without significantly compromising tensile properties. The influence of CVD growth conditions on the single CF tensile properties and carbon nanotube (CNT) morphology was investigated. The experimental results revealed that under high temperature growth conditions, the tensile strength of CF was greatly decreased at the beginning of CNT growth process with the largest decrease observed for sized CFs. However, the tensile strength of unsized CFs with CNT was approximately the same as the initial CF at lower growth temperature. The interfacial shear strength of CNT coated CF (CNT/CF) in epoxy was studied by means of the single-fiber fragmentation test. Results of the test indicate an improvement in interfacial shear strength with the addition of a CNT coating. This improvement can most likely be attributed to an increase in the interphase yield strength as well as an improvement in interfacial adhesion due to the presence of the nanotubes. CNT/CF also offers promise as stress and strain sensors in CF reinforced composite materials. This study investigates fundamental mechanical and electrical properties of CNT/CF using nanoindentation method by designed localized transverse compression at low loads (muN to mN) and small displacements (nm to a few mum). Force, strain, stiffness, and electrical resistance were monitored simultaneously during compression experiments. The results showed that CNT/CF possess a high sensing capability between force and resistance. Hysteresis in both force-displacement and resistance-displacement curves was observed with CNT/CF, but was more evident as maximum strain increased and did not depend on strain rate. Force was higher and resistance was lower during compression as compared to decompression. A model is proposed to explain hysteresis where van der Waals forces between deformed and entangled nanotubes hinder decompression of some of the compressed tubes that are in contact with each other. This study provides a new understanding of the mechanical and electrical behavior of CNT/CF that will facilitate usage as stress and strain sensors in both stand-alone and composite materials applications. A novel method for in situ observation of nano-micro scale CNT/CF mechanical behavior by SEM has been developed in this study. The results indicated that deformation of vertical aligned CNT (VACNT) forest followed a column-like bending mechanism under localized radial (axial) compression. No fracture was observed even at very high compression strain on a VACNT forest. In order to fully understand CNT forest properties, the viscous creep behavior of VACNT arrays grown on flat Si substrate has also been characterized using a nanoindentation method. Resulting creep response was observed to consist of a short transient stage and a steady state stage in which the rate of displacement was constant. The strain rate sensitivity depended on the density of the nanotube arrays, but it was independent of the ramping (compression) rate of the indenter.

The Role Of Contact Force In Atrial Fibrillation Ablation.

PubMed

Nakagawa, Hiroshi; Jackman, Warren M

2014-01-01

During radiofrequency (RF) ablation, low electrode-tissue contact force (CF) is associated with ineffective RF lesion formation, whereas excessive CF may increase the risk of steam pop and perforation. Recently, ablation catheters using two technologies have been developed to measure real-time catheter-tissue CF. One catheter uses three optical fibers to measure microdeformation of a deformable body in the catheter tip. The other catheter uses a small spring connecting the ablation tip electrode to the catheter shaft with a magnetic transmitter and sensors to measure microdeflection of the spring. Pre-clinical experimental studies have shown that 1) at constant RF power and application time, RF lesion size significantly increases with increasing CF; 2) the incidence of steam pop and thrombus also increase with increasing CF; 3) modulating RF power based on CF (i.e, high RF power at low CF and lower RF power at high CF) results in a similar and predictable RF lesion size. In clinical studies in patients undergoing pulmonary vein (PV) isolation, CF during mapping in the left atrium and PVs showed a wide range of CF and transient high CF. The most common high CF site was located at the anterior/rightward left atrial roof, directly beneath the ascending aorta. There was a poor relationship between CF and previously used surrogate parameters for CF (unipolar or bipolar atrial potential amplitude and impedance). Patients who underwent PV isolation with an average CF of <10 g experienced higher AF recurrence, whereas patients with ablation using an average CF of > 20g had lower AF recurrence. AF recurred within 12 months in 6 of 8 patients (75%) who had a mean Force-Time Integral (FTI, area under the curve for contact force vs. time) < 500 gs. In contrast, AF recurred in only 4 of 13 patients (21%) with ablation using a mean FTI >1000 gs. In another study, controlling RF power based on CF prevented steam pop and impedance rise without loss of lesion effectiveness. These studies confirm that CF is a major determinant of RF lesion size and future systems combining CF, RF power and application time may provide real-time assessment of lesion formation.

O(1D) kinetic study of key ozone depleting substances and greenhouse gases.

PubMed

Baasandorj, Munkhbayar; Fleming, Eric L; Jackman, Charles H; Burkholder, James B

2013-03-28

A key stratospheric loss process for ozone depleting substances (ODSs) and greenhouse gases (GHGs) is reaction with the O((1)D) atom. In this study, rate coefficients, k, for the O((1)D) atom reaction were measured for the following key halocarbons: chlorofluorocarbons (CFCs) CFCl3 (CFC-11), CF2Cl2 (CFC-12), CFCl2CF2Cl (CFC-113), CF2ClCF2Cl (CFC-114), CF3CF2Cl (CFC-115); hydrochlorofluorocarbons (HCFCs) CHF2Cl (HCFC-22), CH3CClF2 (HCFC-142b); and hydrofluorocarbons (HFCs) CHF3 (HFC-23), CHF2CF3 (HFC-125), CH3CF3 (HFC-143a), and CF3CHFCF3 (HFC-227ea). Total rate coefficients, kT, corresponding to the loss of the O((1)D) atom, were measured over the temperature range 217-373 K using a competitive reactive technique. kT values for the CFC and HCFC reactions were >1 × 10(-10) cm(3) molecule(-1) s(-1), except for CFC-115, and the rate coefficients for the HFCs were in the range (0.095-0.72) × 10(-10) cm(3) molecule(-1) s(-1). Rate coefficients for the CFC-12, CFC-114, CFC-115, HFC-23, HFC-125, HFC-143a, and HFC-227ea reactions were observed to have a weak negative temperature dependence, E/R ≈ -25 K. Reactive rate coefficients, kR, corresponding to the loss of the halocarbon, were measured for CFC-11, CFC-115, HCFC-22, HCFC-142b, HFC-23, HFC-125, HFC-143a, and HFC-227ea using a relative rate technique. The reactive branching ratio obtained was dependent on the composition of the halocarbon and the trend in O((1)D) reactivity with the extent of hydrogen and chlorine substitution is discussed. The present results are critically compared with previously reported kinetic data and the discrepancies are discussed. 2D atmospheric model calculations were used to evaluate the local and global annually averaged atmospheric lifetimes of the halocarbons and the contribution of O((1)D) chemistry to their atmospheric loss. The O((1)D) reaction was found to be a major global loss process for CFC-114 and CFC-115 and a secondary global loss process for the other molecules included in this study.

Carbon nanotubes/carbon fiber hybrid material: a super support material for sludge biofilms.

PubMed

Liu, Qijie; Dai, Guangze; Bao, Yanling

2017-07-16

Carbon fiber (CF) is widely used as a sludge biofilm support material for wastewater treatment. Carbon nanotubes/carbon fiber (CNTs/CF) hybrid material was prepared by ultrasonically assisted electrophoretic deposition (EPD). CF supports (CF without handling, CF oxidized by nitric acid, CNTs/CF hybrid material) were evaluated by sludge immobilization tests, bacterial cell adsorption tests and Derjaguin -Landau -Verwey -Overbeek (DLVO) theory. We found that the CNTs/CF hybrid material has a high capacity for adsorbing activated sludge, nitrifying bacterial sludge and pure strains (Escherichia coli and Staphylococcus aureus). CNTs deposited on CF surface easily wound around the curved surface of bacterial cell which resulted in capturing more bacterial cells. DLVO theory indicated the lowest total interaction energy of CNTs/CF hybrid material, which resulted in the highest bacteria cell adsorption velocity. Experiments and DLVO theory results proved that CNTs/CF hybrid material is a super support material for sludge biofilms.

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

Nitramine Composite Solid Propellant Modelling

DTIC Science & Technology

1989-07-01

nonshaded areas, Sox values of zero are calculated for the various configurations indicated. The upper shaded area corresponds to one- half cf the...results: QDX ST Q X P F -XP QX "X TsX - To Gs X+ + Cf l sT),X +(l-Xf) ,X (134) In the above equations, and in the ones that follow, the solid phase...Surface Warfare Center, White Oak Laboratory, Silver Spring Code R10, S. Jacobs (1) Code R16, Dr. G. B. Wilmot (1) 1 Naval Underwater Systems Center

The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer.

PubMed

Krupke, Debra M; Begley, Dale A; Sundberg, John P; Richardson, Joel E; Neuhauser, Steven B; Bult, Carol J

2017-11-01

Research using laboratory mice has led to fundamental insights into the molecular genetic processes that govern cancer initiation, progression, and treatment response. Although thousands of scientific articles have been published about mouse models of human cancer, collating information and data for a specific model is hampered by the fact that many authors do not adhere to existing annotation standards when describing models. The interpretation of experimental results in mouse models can also be confounded when researchers do not factor in the effect of genetic background on tumor biology. The Mouse Tumor Biology (MTB) database is an expertly curated, comprehensive compendium of mouse models of human cancer. Through the enforcement of nomenclature and related annotation standards, MTB supports aggregation of data about a cancer model from diverse sources and assessment of how genetic background of a mouse strain influences the biological properties of a specific tumor type and model utility. Cancer Res; 77(21); e67-70. ©2017 AACR . ©2017 American Association for Cancer Research.

Defective Fluid Secretion from Submucosal Glands of Nasal Turbinates from CFTR-/- and CFTRΔF508/ΔF508 Pigs

PubMed Central

Cho, Hyung-Ju; Joo, Nam Soo; Wine, Jeffrey J.

2011-01-01

Background Cystic fibrosis (CF), caused by reduced CFTR function, includes severe sinonasal disease which may predispose to lung disease. Newly developed CF pigs provide models to study the onset of CF pathophysiology. We asked if glands from pig nasal turbinates have secretory responses similar to those of tracheal glands and if CF nasal glands show reduced fluid secretion. Methodology/Principal Findings Unexpectedly, we found that nasal glands differed from tracheal glands in five ways, being smaller, more numerous (density per airway surface area), more sensitive to carbachol, more sensitive to forskolin, and nonresponsive to Substance P (a potent agonist for pig tracheal glands). Nasal gland fluid secretion from newborn piglets (12 CF and 12 controls) in response to agonists was measured using digital imaging of mucus bubbles formed under oil. Secretion rates were significantly reduced in all conditions tested. Fluid secretory rates (Controls vs. CF, in pl/min/gland) were as follows: 3 µM forskolin: 9.2±2.2 vs. 0.6±0.3; 1 µM carbachol: 143.5±35.5 vs. 52.2±10.3; 3 µM forskolin + 0.1 µM carbachol: 25.8±5.8 vs. CF 4.5±0.9. We also compared CFΔF508/ΔF508 with CFTR-/- piglets and found significantly greater forskolin-stimulated secretion rates in the ΔF508 vs. the null piglets (1.4±0.8, n = 4 vs. 0.2±0.1, n = 7). An unexpected age effect was also discovered: the ratio of secretion to 3 µM forskolin vs. 1 µM carbachol was ∼4 times greater in adult than in neonatal nasal glands. Conclusions/Significance These findings reveal differences between nasal and tracheal glands, show defective fluid secretion in nasal glands of CF pigs, reveal some spared function in the ΔF508 vs. null piglets, and show unexpected age-dependent differences. Reduced nasal gland fluid secretion may predispose to sinonasal and lung infections. PMID:21935358

Background and Epidemiology

PubMed Central

Sanders, Don B.; Fink, Aliza

2016-01-01

SYNOPSIS Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. Significant advances in therapies and outcomes have occurred for people with CF over the past 30 years. Many of these improvements have come about through the concerted efforts of the US CF Foundation and international CF societies, networks of CF care centers, and the worldwide community of care providers, researchers, and patients and families. Despite these gains, there are still hurdles to overcome to continue to improve the quality of life, reduce CF complications, prolong survival, and ultimately cure CF. This article reviews the epidemiology of CF, including trends in incidence and prevalence, clinical characteristics, common complications, and survival. PMID:27469176

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.

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.

Two novel LRR-only proteins in Chlamys farreri: Similar in structure, yet different in expression profile and pattern recognition.

PubMed

Wang, Mengqiang; Wang, Lingling; Xin, Lusheng; Wang, Xiudan; Wang, Lin; Xu, Jianchao; Jia, Zhihao; Yue, Feng; Wang, Hao; Song, Linsheng

2016-06-01

Leucine-rich repeat (LRR)-only proteins could mediate protein-ligand and protein-protein interactions and be involved in the immune response. In the present study, two novel LRR-only proteins, CfLRRop-2 and CfLRRop-3, were identified and characterized from scallop Chlamys farreri. They both contained nine LRR motifs with the consensus signature sequence LxxLxLxxNxL and formed typical horseshoe structure. The CfLRRop-2 and CfLRRop-3 mRNA transcripts were constitutively expressed in haemocytes, muscle, mantle, gill, haepatopancreas and gonad, with the highest expression level in haepatopancreas and gill, respectively. During the ontogenesis of scallop, the mRNA transcripts of CfLRRop-2 were kept at a high level in oocytes and embryos, while those of CfLRRop-3 were expressed at a rather low level from oocytes to blastula. Their mRNA transcripts were significantly increased after the stimulation of lipopolysaccharide (LPS), peptidoglycan (PGN), glucan (GLU) and polyinosinic-polycytidylic acid (poly I:C), and the mRNA expression of CfLRRop-2 rose more intensely than that of CfLRRop-3. After the suppression of CfTLR (previously identified Toll-like receptor in C. farreri) via RNA interference (RNAi), CfLRRop-3 mRNA transcripts increased more intensely and lastingly than those of CfLRRop-2. The rCfLRRop-3 protein could bind LPS, PGN, GLU and poly I:C, while rCfLRRop-2 exhibited no significant binding activity to them. Additionally, rCfLRRop-2 could significantly induce the release of TNF-α from the mixed primary cultured scallop haemocytes, but rCfLRRop-3 failed. These results collectively indicated that CfLRRop-2 might act as an immune effector or pro-inflammatory factor, while CfLRRop-3 would function as a pattern recognition receptor (PRR), suggesting the function of LRR-only protein family has differentiated in scallop. Copyright © 2016 Elsevier Ltd. All rights reserved.

Perceived needs for different components in a rehabilitation program among cancer survivors with chronic fatigue compared to survivors without chronic fatigue.

PubMed

Gjerset, Gunhild M; Loge, Jon H; Kiserud, Cecilie E; Fosså, Sophie D; Gudbergsson, Sævar B; Oldervoll, Line M; Wisløff, Torbjørn; Thorsen, Lene

2017-02-01

Knowledge about the user' needs is important to develop targeted rehabilitation for cancer patients with chronic fatigue (CF). The aims of the study were to examine prevalence of CF in cancer survivors attending an one-week inpatient educational program (IEP) and to identify characteristics of those with CF. Further to examine the perceived needs for different components in a rehabilitation program, need of complex rehabilitation (at least two components) and aspects of health-related quality of life (HRQoL) among survivors with CF versus those without CF. Cancer survivors ≥18 years, diagnosed with different types of cancer within the last 10 years and attending a one-week IEP were invited to this cross-sectional study. CF was assessed by the Fatigue Questionnaire, perceived needs by asking a question about needs for different components in a rehabilitation program and HRQoL was assessed by The Medical Outcomes Study Short Form 36. Of 564 participants, 45% reported CF. Breast cancer, mixed cancer types (including small groups with different cancer types) and comorbidities increased the risk for having CF. Compared to participants without CF, the participants with CF reported more frequently need for physical training (86% vs. 65%, p < 0.001), physiotherapy (71% vs. 55%, p < 0.001) and nutrition counseling (68% vs. 53%, p = 0.001). Among participants with CF, 75% reported need for three or more components whereas 54% reported need for the same number of components among those without CF (p < 0.001). Almost half of the cancer survivors attending the IEP had CF. Physical training, physiotherapy and nutrition counseling were the most frequently reported needs and significantly more often observed in participants with CF than without CF. A higher percentage of those with CF reported need for a complex rehabilitation compared to those without CF. More research is necessary to obtain more knowledge to further make targeted programs to better match cancer survivors' needs.

Comparing the Caputo, Caputo-Fabrizio and Atangana-Baleanu derivative with fractional order: Fractional cubic isothermal auto-catalytic chemical system

NASA Astrophysics Data System (ADS)

Saad, K. M.

2018-03-01

In this work we extend the standard model for a cubic isothermal auto-catalytic chemical system (CIACS) to a new model of a fractional cubic isothermal auto-catalytic chemical system (FCIACS) based on Caputo (C), Caputo-Fabrizio (CF) and Atangana-Baleanu in the Liouville-Caputo sense (ABC) fractional time derivatives, respectively. We present approximate solutions for these extended models using the q -homotopy analysis transform method ( q -HATM). We solve the FCIACS with the C derivative and compare our results with those obtained using the CF and ABC derivatives. The ranges of convergence of the solutions are found and the optimal values of h , the auxiliary parameter, are derived. Finally, these solutions are compared with numerical solutions of the various models obtained using finite differences and excellent agreement is found.

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.

Induction of colonic aberrant crypts in mice by feeding apparent N-nitroso compounds derived from hot dogs

PubMed Central

Davis, Michael E; Lisowyj, Michal P; Zhou, Lin; Wisecarver, James L; Gulizia, James M; Shostrom, Valerie K; Naud, Nathalie; Corpet, Denis E; Mirvish, Sidney S

2012-01-01

Nitrite-preserved meats (e.g., hot dogs) may help cause colon cancer because they contain N-nitroso compounds. We tested whether purified hot-dog-derived total apparent N-nitroso compounds (ANC) could induce colonic aberrant crypts, which are putative precursors of colon cancer. We purified ANC precursors in hot dogs and nitrosated them to produce ANC. In preliminary tests, CF1 mice received 1 or 3 i.p. injections of 5mg azoxymethane (AOM)/kg. In Experiments 1 and 2, female A/J mice received ANC in diet. In Experiment 1, ANC dose initially dropped sharply because the ANC precursors had mostly decomposed but, later in Experiment 1 and throughout Experiment 2, ANC remained at 85 nmol/g diet. Mice were killed after 8 (AOM tests) or 17–34 (ANC tests) wk. Median numbers of aberrant crypts in the distal 2 cm of the colon for 1 and 3 AOM injections, CF1 controls, ANC (Experiment 1), ANC (Experiment 2),and untreated A/J mice were 31, 74, 12, 20, 12, and 5–6, with P < 0.01 for both ANC tests. Experiment 2 showed somewhat increased numbers of colonic mucin-depleted foci in the ANC-treated group. We conclude that hot-dog-derived ANC induced significant numbers of aberrant crypts in the mouse colon. PMID:22293095

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.

Finite Element Analysis of Bone Stress around Micro-Implants of Different Diameters and Lengths with Application of a Single or Composite Torque Force.

PubMed

Lu, Ying-juan; Chang, Shao-hai; Ye, Jian-tao; Ye, Yu-shan; Yu, Yan-song

2015-01-01

Stress on the bone surrounding dental micro-implants affects implant success. To compare the stress on the bone surrounding a micro-implant after application of a single force (SF) of 200 g or a composite force (CF) of 200 g and 6 N.mm torque. Finite element models were developed for micro-implant diameters of 1.2, 1.6, and 2.0 mm, and lengths of 6, 8, 10, and 12 mm and either a SF or CF was applied. The maximum equivalent stress (Max EQS) of the bone surrounding the micro-implant was determined, and the relationships among type of force, diameter, and length were evaluated. The Max EQS of the CF exceeded that of the SF (P< 0.05). The effect of force on stress was related to implant diameter, but not to implant length. The larger CF led to greater instability of the micro-implant and the effect was most pronounced at an implant diameter of 1.2 mm. The use of implant diameters of 1.6 mm and 2.0 mm produced no significant difference in implant stability when either a CF or SF was applied. When considering the use of an implant to perform three-dimensional control on the teeth, the implant diameter chosen should be > 1.2 mm.

Finite Element Analysis of Bone Stress around Micro-Implants of Different Diameters and Lengths with Application of a Single or Composite Torque Force

PubMed Central

Lu, Ying-juan; Chang, Shao-hai; Ye, Jian-tao; Ye, Yu-shan; Yu, Yan-song

2015-01-01

Background Stress on the bone surrounding dental micro-implants affects implant success. Purpose To compare the stress on the bone surrounding a micro-implant after application of a single force (SF) of 200 g or a composite force (CF) of 200 g and 6 N.mm torque. Materials and Methods Finite element models were developed for micro-implant diameters of 1.2, 1.6, and 2.0 mm, and lengths of 6, 8, 10, and 12 mm and either a SF or CF was applied. The maximum equivalent stress (Max EQS) of the bone surrounding the micro-implant was determined, and the relationships among type of force, diameter, and length were evaluated. Results The Max EQS of the CF exceeded that of the SF (P< 0.05). The effect of force on stress was related to implant diameter, but not to implant length. The larger CF led to greater instability of the micro-implant and the effect was most pronounced at an implant diameter of 1.2 mm. The use of implant diameters of 1.6 mm and 2.0 mm produced no significant difference in implant stability when either a CF or SF was applied. Conclusion When considering the use of an implant to perform three-dimensional control on the teeth, the implant diameter chosen should be > 1.2 mm. PMID:26659581

Cystic fibrosis mortality trends in Spain among infants and young children: 1981-2004.

PubMed

Ramalle-Gomara, Enrique; Perucha, Milagros; González, María-Angeles; Quiñones, Carmen; Andrés, Jesús; Posada, Manuel

2008-01-01

This paper sought to analyse mortality trends among infants and young children who died with a diagnosis of cystic fibrosis (CF) in Spain, during the period 1981-2004. Descriptive observational study, using joinpoint regression models. Data on cystic fibrosis deaths were drawn from the National Statistics Institute (Instituto Nacional de Estadística), which collects data from all death certificates in Spain. During the period 1981-2004, overall CF mortality in Spain decreased by an annual average of 4% in both sexes. A breakdown by age showed that patients under 15 years registered a declining and those over 15 years a rising mortality rate over the study period. Mean and median age at death from CF increased with time, from a median of 4.4 years (males) and 3.8 years (females) in 1981 to 20.1 years (males) and 17.7 years (females) in 2004. The results of this study show that, as in other Western countries, CF is no longer a major cause of death in childhood, and that the challenge now lies in caring for adults who suffer from this disease. The fact that our study was descriptive meant that the reasons for the decrease in CF mortality in Spain could not be identified. Other authors have shown that this decrease is associated with improved treatment for pulmonary complications, better nutritional control and lung transplants.

Analyzing Fish Condition Factor Index Through Skew-Gaussian Information Theory Quantifiers

NASA Astrophysics Data System (ADS)

Contreras-Reyes, Javier E.

2016-06-01

Biological-fishery indicators have been widely studied. As such the condition factor (CF) index, which interprets the fatness level of a certain species based on length and weight, has been investigated, too. However, CF has been studied without considering its temporal features and distribution. In this paper, we analyze the CF time series via skew-gaussian distributions that consider the asymmetry produced by extreme events. This index is characterized by a threshold autoregressive model and corresponds to a stationary process depending on the shape parameter of the skew-gaussian distribution. Then we use the Jensen-Shannon (JS) distance to compare CF by length classes. This distance has mathematical advantages over other divergences such as Kullback-Leibler and Jeffrey’s, and the triangular inequality property. Our results are applied to a biological catalogue of anchovy (Engraulis ringens) from the northern coast of Chile, for the period 1990-2010 that consider monthly CF time series by length classes and sex. We find that for high values of shape parameter, JS distance tends to be more sensible to detect discrepancies than Jeffrey’s divergence. In addition, the body condition of male anchovies with higher lengths coincides with the ending of the moderate-strong El Niño event 91-92 and for both males and females, the smaller lengths coincide with the beginning of the strong El Niño event 97-98.

Examination of Scanning Electron Microscope and Computed Tomography Images of PICA

NASA Technical Reports Server (NTRS)

Lawson, John W.; Stackpoole, Margaret M.; Shklover, Valery

2010-01-01

Micrographs of PICA (Phenolic Impregnated Carbon Ablator) taken using a Scanning Electron Microscope (SEM) and 3D images taken with a Computed Tomography (CT) system are examined. PICA is a carbon fiber based composite (Fiberform ) with a phenolic polymer matrix. The micrographs are taken at different surface depths and at different magnifications in a sample after arc jet testing and show different levels of oxidative removal of the charred matrix (Figs 1 though 13). CT scans, courtesy of Xradia, Inc. of Concord CA, were captured for samples of virgin PICA, charred PICA and raw Fiberform (Fig. 14). We use these images to calculate the thermal conductivity (TC) of these materials using correlation function (CF) methods. CF methods give a mathematical description of how one material is embedded in another and is thus ideally suited for modeling composites like PICA. We will evaluate how the TC of the materials changes as a function of surface depth. This work is in collaboration with ETH-Zurich, which has expertise in high temperature materials and TC modeling (including CF methods).

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...

Disease duration of rheumatoid arthritis is a predictor of vascular stiffness: a cross-sectional study in patients without known cardiovascular comorbidities

PubMed Central

Vázquez-Del Mercado, Mónica; Gomez-Bañuelos, Eduardo; Chavarria-Avila, Efrain; Cardona-Muñoz, Ernesto; Ramos-Becerra, Carlos; Alanis-Sanchez, Adrián; Cardona-Muller, David; Grover-Paez, Fernando; Perez-Vazquez, Felipe de J.; Navarro-Hernandez, Rosa-Elena; Valadez-Soto, Jorge M.; Saldaña-Millan, Adan A.; Gonzalez-Rosas, Lorena; Ramos-Lopez, Gabriel; Petri, Marcelo H.; Bäck, Magnus

2017-01-01

Abstract The aim of this study was to analyze the impact of disease duration on carotid to femoral pulse wave velocity (cfPWV) in rheumatoid arthritis (RA) patients without either known traditional cardiovascular risk factors or previous comorbidities. Patients with RA diagnosis attending the rheumatology outpatient clinic of Hospital Civil Juan I. Menchaca, Guadalajara, Mexico, were analyzed. A total of 106 RA patients without known traditional cardiovascular risk factors were selected. All subjects were evaluated for RA disease duration, RA disease activity score on 28 joints (DAS28), serum lipids, rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Arterial stiffness was measured as cfPWV by noninvasive tonometry. A multivariate regression model was used to analyze the contribution of RA disease duration and age on cfPWV. cfPWV was positively correlated with age (r = 0.450, P < .001), RA disease duration (r = 0.340, P < .001), total cholesterol (r = 0.312, P = .002), and low density lipoprotein (LDL-c) cholesterol (r = 0.268, P = .012). Patients with a RA disease duration ≥10 years exhibited significantly increased cfPWV compared with patients with disease duration <2 years (8.4 ± 1.8 vs 7.0 ± 0.8) and ≥2 to <10 years (8.4 ± 1.8 vs 7.8 ± 1.3), respectively. Age, RA disease duration, and triglycerides were predictors of cfPWV in multivariate analyses. According to the β-coefficients, each year of disease duration (β = 0.072) had a greater impact on cfPWV than age (β = 0.054). Each year of life with RA contributes to a higher rate of vascular aging or stiffening than a year of life without RA. The cumulative damage provided by RA was most pronounced in patients with disease duration ≥10 years. PMID:28816989

High-intensity exercise of short duration alters bovine bone density and shape.

PubMed

Hiney, K M; Nielsen, B D; Rosenstein, D; Orth, M W; Marks, B P

2004-06-01

The ability of short-duration high-intensity exercise to stimulate bone formation in confinement was investigated using immature Holstein bull calves as a model. Eighteen bull calves, 8 wk of age, were assigned to one of three treatment groups: 1) group-housed (GR, which served as a control), 2) confined with no exercise (CF), or 3) confined with exercise (EX). The exercise protocol consisted of running 50 m on a concrete surface once daily, 5 d/wk. Confined calves remained stalled for the 42-d duration of the trial. Blood samples were taken to analyze concentrations of osteocalcin and deoxypyridinoline, markers of bone formation and resorption. At the completion of the trial, calves were humanely killed, and both forelegs were collected. The fused third and fourth metacarpal bone was scanned using computed tomography for determination of cross-sectional geometry and bone mineral density. Three-point bending tests to failure were performed on metacarpal bones. The exercise protocol resulted in the formation of a rounder bone in EX as well as in increased dorsal cortex thickness compared with those in the GR and CF. The exercised calves had a significantly smaller medullary cavity than CF and GR (P < 0.01) and a larger percentage of cortical bone area than CF (P < 0.01). Dorsal, palmar, and total bone mineral density was greater in EX than in CF (P < 0.05), and palmar and total bone mineral densities were greater (P < 0.05) in EX than in GR. There was a trend for the bones of EX to have a higher fracture force than CF (P < 0.10). Osteocalcin concentrations normalized from d 0 were higher in EX than CF (P < 0.05). Therefore, the exercise protocol altered bone shape and seemed to increase bone formation comparison with the stalled and group-housed calves.

Pulmonary function disparities exist and persist in Hispanic patients with cystic fibrosis: A longitudinal analysis.

PubMed

McGarry, Meghan E; Neuhaus, John M; Nielson, Dennis W; Burchard, Esteban; Ly, Ngoc P

2017-12-01

Hispanic patients with cystic fibrosis (CF) have decreased life expectancy compared to non-Hispanic white patients. Pulmonary function is a main predictor of life expectancy in CF. Ethnic differences in pulmonary function in CF have been understudied. The objective was to compare longitudinal pulmonary function between Hispanic and non-Hispanic white patients with CF. This cohort study of 15 018 6-25 years old patients in the CF Foundation Patient Registry from 2008 to 2013 compared FEV 1 percent predicted and longitudinal change in FEV 1 percent predicted in Hispanic to non-Hispanic white patients. We used linear mixed effects models with patient-specific slopes and intercepts, adjusting for 14 demographic and clinical variables. We did sub-analyses by CFTR class, F508del copies, and PERT use. Hispanic patients had lower FEV 1 percent predicted (79.9%) compared with non-Hispanic white patients (85.6%); (-5.8%, 95%CI -6.7% to -4.8%, P < 0.001), however, there was no difference in FEV 1 decline over time. Patients on PERT had a larger difference between Hispanic and non-Hispanic white patients in FEV 1 percent predicted than patients not on PERT (-6.0% vs -4.1%, P = 0.02). The ethnic difference in FEV 1 percent predicted was not statistically significant between CFTR classes (Class I-III: -6.1%, Class IV-V: -5.9%, Unclassified: -5.7%, P > 0.05) or between F508del copies (None: -7.6%, Heterozygotes: -5.6%, Homozygotes: -5.3%, P > 0.05). Disparities in pulmonary function exist in Hispanic patients with CF early in life and then persist without improving or worsening over time. It is valuable to investigate the factors contributing to pulmonary function in Hispanic patients with CF. © 2017 Wiley Periodicals, Inc.

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.

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.

Use of Less Reactive Materials and More Stable Gases to Reduce Corrosive Wear When Lubricating with Halogenated Gases

NASA Technical Reports Server (NTRS)

Buckley, Donald H.; Johnson, Robert L.

1960-01-01

The gases CF2Cl-CF2Cl, CF2Cl2, and CF2Br-CF2Br were used to lubricate metals, cermets, and ceramics in this study. One of the criteria for determining the effectiveness of a reactive-gas-lubricated systems is the stability of the halogen-containing gas molecule. The carbon-to-halogen bond in the ethane molecule has extremely good thermal stability superior to the methane analogs (CF2Cl2 and CF2Br2) used in earlier research. For this reason, the ethane compounds CF2Cl-CF2Cl and CF2Br-CF2Br were considered as high-temperature lubricants. Friction and wear studies were made with a hemisphere (3/16-in. rad.) rider sliding in a circumferential path on the flat surface of a rotating disk (21/2-in. diam. ). The specimens of metal alloys, cermets, and ceramics were run In an atmosphere of the various gases with a load of 1200 grams, sliding velocities from 75 to 8000 feet per minute, and temperatures from 75 to 1400 F. The gas CF2Cl-CF2Cl was found to be an effective lubricant for the cermet LT-LB (59.0 Cr, 19.0 Al2O3, 20.0 Mo, 2.0 Ti) and the ceramic Al2O3 sliding on Stellite Star J (cobalt-base alloy) at temperatures to 1400 F. The bromine-containing gas CF2Br-CF2Br was found to give friction and wear values that can be considered to be in a region of effective boundary lubrication for the cermet K175D (nickel-bonded metal carbide) sliding on the metal Hastelloy R-235 (nickel-base alloy) at temperatures to 1200 F.

Structural and kinetic study of reversible CO2 fixation by dicopper macrocyclic complexes. From intramolecular binding to self-assembly of molecular boxes.

PubMed

Company, Anna; Jee, Joo-Eun; Ribas, Xavi; Lopez-Valbuena, Josep Maria; Gómez, Laura; Corbella, Montserrat; Llobet, Antoni; Mahía, José; Benet-Buchholz, Jordi; Costas, Miquel; van Eldik, Rudi

2007-10-29

A study of the reversible CO2 fixation by a series of macrocyclic dicopper complexes is described. The dicopper macrocyclic complexes [Cu2(OH)2(Me2p)](CF3SO3)2, 1(CF3SO3)2, and [Cu2(mu-OH)2(Me2m)](CF3SO3)2, 2(CF3SO3)2, (Scheme 1) containing terminally bound and bridging hydroxide ligands, respectively, promote reversible inter- and intramolecular CO2 fixation that results in the formation of the carbonate complexes [{Cu2(Me2p)}2(mu-CO3)2](CF3SO3)4, 4(CF3SO3)4, and [Cu2(mu-CO3)(Me2m)](CF3SO3)2, 5(CF3SO3)2. Under a N2 atmosphere the complexes evolve CO2 and revert to the starting hydroxo complexes 1(CF3SO3)2 and 2(CF3SO3)2, a reaction the rate of which linearly depends on [H2O]. In the presence of water, attempts to crystallize 5(CF3SO3)2 afford [{Cu2(Me2m)(H2O)}2(mu-CO3)2](CF3SO3)4, 6(CF3SO3)4, which appears to rapidly convert to 5(CF3SO3)2 in acetonitrile solution. [Cu2(OH)2(H3m)]2+, 7, which contains a larger macrocyclic ligand, irreversibly reacts with atmospheric CO2 to generate cagelike [{Cu2(H3m)}2(mu-CO3)2](ClO4)4, 8(ClO4)4. However, addition of 1 equiv of HClO4 per Cu generates [Cu2(H3m)(CH3CN)4]4+ (3), and subsequent addition of Et3N under air reassembles 8. The carbonate complexes 4(CF3SO3)4, 5(CF3SO3)2, 6(CF3SO3)4, and 8(ClO4)4 have been characterized in the solid state by X-ray crystallography. This analysis reveals that 4(CF3SO3)4, 6(CF3SO3)4, and 8(ClO4)4 consist of self-assembled molecular boxes containing two macrocyclic dicopper complexes, bridged by CO32- ligands. The bridging mode of the carbonate ligand is anti-anti-mu-eta1:eta1 in 4(CF3SO3)4, anti-anti-mu-eta2:eta1 in 6(CF3SO3)4 and anti-anti-mu-eta2:eta2 in 5(CF3SO3)2 and 8(ClO4)4. Magnetic susceptibility measurements on 4(CF3SO3)4, 6(CF3SO3)4, and 8(ClO4)4 indicate that the carbonate ligands mediate antiferromagnetic coupling between each pair of bridged CuII ions (J = -23.1, -108.3, and -163.4 cm-1, respectively, H = -JS1S2). Detailed kinetic analyses of the reaction between carbon dioxide and the macrocyclic complexes 1(CF3SO3)2 and 2(CF3SO3)2 suggest that it is actually hydrogen carbonate formed in aqueous solution on dissolving CO2 that is responsible for the observed formation of the different carbonate complexes controlled by the binding mode of the hydroxy ligands. This study shows that CO2 fixation can be used as an on/off switch for the reversible self-assembly of supramolecular structures based on macrocyclic dicopper complexes.

Actin - Lysozyme Interactions in Model Cystic Fibrosis Sputum

NASA Astrophysics Data System (ADS)

Sanders, Lori; Slimmer, Scott; Angelini, Thomas; Wong, Gerard C. L.

2003-03-01

Cystic fibrosis sputum is a complex fluid consisting of mucin (a glycoprotein), lysozyme (a cationic polypeptide), water, salt, as well as a high concentration of a number of anionic biological polyelectrolytes such as DNA and F-actin. The interactions governing these components are poorly understood, but may have important clinical consequences. For example, the formation of these biological polyelectrolytes into ordered gel phases may contribute significantly to the observed high viscosity of CF sputum. In this work, a number of model systems containing actin, lysozyme, and KCl were created to simulate CF sputum in vitro. These model systems were studied using small angle x-ray scattering and confocal fluorescence microscopy. Preliminary results will be presented. This work was supported by NSF DMR-0071761, the Beckman Young Investigator Program, and the Cystic Fibrosis Foundation.

Pseudomonas aeruginosa Airway Infection Recruits and Modulates Neutrophilic Myeloid-Derived Suppressor Cells

PubMed Central

Öz, Hasan H.; Zhou, Benyuan; Voss, Pina; Carevic, Melanie; Schroth, Carolin; Frey, Nina; Rieber, Nikolaus; Hector, Andreas; Hartl, Dominik

2016-01-01

Pseudomonas aeruginosa is an opportunistic pathogen that causes infections mainly in patients with cystic fibrosis (CF) lung disease. Despite innate and adaptive immune responses upon infection, P. aeruginosa is capable of efficiently escaping host defenses, but the underlying immune mechanisms remain poorly understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that are functionally characterized by their potential to suppress T- and natural killer (NK)-cell responses. Here we demonstrate, using an airway in vivo infection model, that P. aeruginosa recruits and activates neutrophilic MDSCs, which functionally suppress T-cell responses. We further show that the CF gene defect (CF transmembrane conductance regulator, CFTR) modulates the functionality, but not the recruitment or generation of neutrophilic MDSCs. Collectively, we define a mechanism by which P. aeruginosa airway infection undermines host immunity by modulating neutrophilic MDSCs in vivo. PMID:27965936

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...

Multidimensional student skills with collaborative filtering

NASA Astrophysics Data System (ADS)

Bergner, Yoav; Rayyan, Saif; Seaton, Daniel; Pritchard, David E.

2013-01-01

Despite the fact that a physics course typically culminates in one final grade for the student, many instructors and researchers believe that there are multiple skills that students acquire to achieve mastery. Assessment validation and data analysis in general may thus benefit from extension to multidimensional ability. This paper introduces an approach for model determination and dimensionality analysis using collaborative filtering (CF), which is related to factor analysis and item response theory (IRT). Model selection is guided by machine learning perspectives, seeking to maximize the accuracy in predicting which students will answer which items correctly. We apply the CF to response data for the Mechanics Baseline Test and combine the results with prior analysis using unidimensional IRT.

Chitinase activation in patients with fungus-associated cystic fibrosis lung disease.

PubMed

Hector, Andreas; Chotirmall, Sanjay H; Lavelle, Gillian M; Mirković, Bojana; Horan, Deirdre; Eichler, Laura; Mezger, Markus; Singh, Anurag; Ralhan, Anjai; Berenbrinker, Sina; Mack, Ines; Ensenauer, Regina; Riethmüller, Joachim; Graepler-Mainka, Ute; Murray, Michelle A; Griese, Matthias; McElvaney, N Gerry; Hartl, Dominik

2016-10-01

Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with cystic fibrosis (CF)-associated lung disease remains unclear. The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF. Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed. Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF. Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Improvement of absorption enhancing effects of n-dodecyl-beta-D-maltopyranoside by its colon-specific delivery using chitosan capsules.

PubMed

Fetih, Gihan; Lindberg, Sara; Itoh, Katsuhito; Okada, Naoki; Fujita, Takuya; Habib, Fawsia; Artersson, Per; Attia, Mohammed; Yamamoto, Akira

2005-04-11

In general, absorption enhancing effects of various absorption enhancers were greater in the large intestine than those in the small intestinal regions. Therefore, the effectiveness of absorption enhancers is expected to be remarkably observed, if these enhancers can be delivered to the large intestine with some poorly absorbable drugs after oral administration. In this study, therefore, we examined whether chitosan capsules were effective for the colon-specific delivery of a certain absorption enhancer and can improve the absorption enhancing action of the absorption enhancer after oral administration. 5(6)-Carboxyfluorescein (CF) was used as a model drug to investigate the site-dependent effectiveness of various absorption enhancers by an in situ closed loop method. Sodium glycocholate (NaGC), n-dodecyl-beta-d-maltopyranoside (LM), sodium salicylate (NaSal) and sodium caprate (NaCap) were used as models of absorption enhancers in this study. Overall, the absorption enhancing effects of these enhancers for intestinal absorption of CF were greater in the colon than those in the jejunum and the ileum. Especially, among these enhancers tested in this study, LM showed much greater absorption enhancing effect in the colon than in the jejunum and the ileum. Therefore, LM was selected as a model absorption enhancer to examine the effect of chitosan capsules on the absorption enhancing effect of LM. When CF and LM were orally administered to rats using chitosan capsules, the plasma concentration of CF was much higher than those in other dosage forms including solution and gelatin capsules. Therefore, chitosan capsules may be useful carriers for colon-specific delivery of LM, thereby increasing its absorption enhancing effect from the intestinal membranes.

An Etiological Approach to Sexual Offender Assessment: CAse Formulation Incorporating Risk Assessment (CAFIRA).

PubMed

Craig, Leam A; Rettenberger, Martin

2018-05-19

Case formulations (CF) have been the cornerstone of effective practice in clinical psychology since the 1950s and now form one of the core competencies in clinical and forensic assessment. The use of CFs within forensic settings is becoming more relevant when working with offenders who have experienced significant trauma, suffered from personality disorder, and have displayed sexually abusive behavior. Furthermore, most North American and European jurisdictions insist that expert witnesses adopt an idiosyncratic approach to risk assessment and consider the characteristics of the individual as part of a wider formulation of the problem behavior. This article focuses specifically on CF incorporating risk assessment procedures of sexual offenders. While empirical support for the use of risk analysis and formulation in managing offending behavior generally, and sexual offending behavior in particular, is limited, there is mounting evidence to suggest that CF can improve understanding of an individual's problem sexual behaviors. We argue that by integrating risk formulations into the CF provides a conceptually robust link between the etiologically development of the problem sexual behavior and effective assessment and risk management of sexual offenders. As forensic treatment programs increasingly moved toward strength-based approaches, in keeping with the Risk-Need-Responsivity principles Andrews and Bonta (2004), and the Good Lives Model Ward and Stewart (Prof Psychol Res Pract 34:353-60, 2003) of offender rehabilitation, the use of CFs in the assessment, treatment, and management of sexual offenders is indispensable. We present an etiological framework for understanding risk in an individual sexual offender by integrating a case formulation model to include the use of (static, stable, and acute) actuarial and clinical risk assessment measures as well as protective risk factors, referred to as the CAse Formulation Incorporating Risk Assessment (CAFIRA) model.

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.

Comparative Analysis of the Effects of Hydroxysafflor Yellow A and Anhydrosafflor Yellow B in Safflower Series of Herb Pairs Using Prep-HPLC and a Selective Knock-Out Approach.

PubMed

Qu, Cheng; Wang, Lin-Yan; Jin, Wen-Tao; Tang, Yu-Ping; Jin, Yi; Shi, Xu-Qin; Shang, Li-Li; Shang, Er-Xin; Duan, Jin-Ao

2016-11-06

The flower of Carthamus tinctorius L. (Carthami Flos, safflower), important in traditional Chinese medicine (TCM), is known for treating blood stasis, coronary heart disease, hypertension, and cerebrovascular disease in clinical and experimental studies. It is widely accepted that hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (ASYB) are the major bioactive components of many formulae comprised of safflower. In this study, selective knock-out of target components such as HSYA and ASYB by using preparative high performance liquid chromatography (prep-HPLC) followed by antiplatelet and anticoagulation activities evaluation was used to investigate the roles of bioactive ingredients in safflower series of herb pairs. The results showed that both HSYA and ASYB not only played a direct role in activating blood circulation, but also indirectly made a contribution to the total bioactivity of safflower series of herb pairs. The degree of contribution of HSYA in the safflower and its series herb pairs was as follows: Carthami Flos-Ginseng Radix et Rhizoma Rubra (CF-GR) > Carthami Flos-Sappan Lignum (CF-SL) > Carthami Flos-Angelicae Sinensis Radix (CF-AS) > Carthami Flos-Astragali Radix (CF-AR) > Carthami Flos-Angelicae Sinensis Radix (CF-AS) > Carthami Flos-Glycyrrhizae Radix et Rhizoma (CF-GL) > Carthami Flos-Salviae Miltiorrhizae Radix et Rhizoma (CF-SM) > Carthami Flos (CF), and the contribution degree of ASYB in the safflower and its series herb pairs: CF-GL > CF-PS > CF-AS > CF-SL > CF-SM > CF-AR > CF-GR > CF. So, this study provided a significant and effective approach to elucidate the contribution of different herbal components to the bioactivity of the herb pair, and clarification of the variation of herb-pair compatibilities. In addition, this study provides guidance for investigating the relationship between herbal compounds and the bioactivities of herb pairs. It also provides a scientific basis for reasonable clinical applications and new drug development on the basis of the safflower series of herb pairs.

Di/mono-nuclear iron(I)/(II) complexes as functional models for the 2Fe2S subunit and distal Fe moiety of the active site of [FeFe] hydrogenases: protonations, molecular structures and electrochemical properties.

PubMed

Gao, Shang; Fan, Jiangli; Sun, Shiguo; Song, Fengling; Peng, Xiaojun; Duan, Qian; Jiang, Dayong; Liang, Qingcheng

2012-10-21

Di/mono-nuclear iron(I)/(II) complexes containing conjugated and electron-withdrawing S-to-S linkers, [{(μ-S)(2)(C(4)N(2)H(2))}Fe(2)(CO)(6)] (1), [{(μ-S)(2)(C(4)N(2)H(2))}Fe(2)(CO)(5)(PMe(3))] (1P), and [{(μ-S)(2)(C(4)N(2)H(2))}Fe(CO)(2)(PMe(3))(2)] (2) were prepared as biomimetic models for the 2Fe2S subunit and distal Fe moiety of the active site of [FeFe] hydrogenases. The N atoms in the heterocyclic pyrazines of 1 and 2 were protonated in the presence of proton acid to generate one and two hydrides, [1(NH)](+) CF(3)SO(3)(-), [2(NH)](+) CF(3)SO(3)(-), and [2(NH)(2)](2+) (CF(3)SO(3)(-))(2), respectively. The protonation processes were evidenced by in situ IR and NMR spectroscopy. The molecular structures of the protonated species [1(NH)](+) CF(3)SO(3)(-) and [2(NH)(2)](2+) (CF(3)SO(3)(-))(2) together with their originating complexes and , and the mono-PMe(3) substituted diiron complex were identified by X-ray crystallography. The IR and single-crystal analysis data all suggested that the electron-withdrawing bridge, pyrazine, led to decreased electron density at the Fe centers of the model complexes, which was consistent with the electrochemical studies. The cyclic voltammograms indicated that complex exhibited a low primary reduction potential at -1.17 V vs. Fc-Fc(+) with a 270 mV positive shift compared with that of the benzene-1,2-dithiolate (bdt) bridged analogue [(μ-bdt)Fe(2)(CO)(6)]. Under the weak acid conditions, complexes 1 and 2 could electrochemically catalyze the proton reduction. More interestingly, the mononuclear ferrous complex 2 showed two catalytic peaks during the formation of hydrogen, confirming its potential as a catalyst for hydrogen production.

The use of linear programming to determine whether a formulated complementary food product can ensure adequate nutrients for 6- to 11-month-old Cambodian infants.

PubMed

Skau, Jutta K H; Bunthang, Touch; Chamnan, Chhoun; Wieringa, Frank T; Dijkhuizen, Marjoleine A; Roos, Nanna; Ferguson, Elaine L

2014-01-01

A new software tool, Optifood, developed by the WHO and based on linear programming (LP) analysis, has been developed to formulate food-based recommendations. This study discusses the use of Optifood for predicting whether formulated complementary food (CF) products can ensure dietary adequacy for target populations in Cambodia. Dietary data were collected by 24-h recall in a cross-sectional survey of 6- to 11-mo-old infants (n = 78). LP model parameters were derived from these data, including a list of foods, median serving sizes, and dietary patterns. Five series of LP analyses were carried out to model the target population's baseline diet and 4 formulated CF products [WinFood (WF), WinFood-Lite (WF-L), Corn-Soy-Blend Plus (CSB+), and Corn-Soy-Blend Plus Plus (CSB++)], which were added to the diet in portions of 33 g/d dry weight (DW) for infants aged 6-8 mo and 40 g/d DW for infants aged 9-11 mo. In each series of analyses, the nutritionally optimal diet and theoretical range, in diet nutrient contents, were determined. The LP analysis showed that baseline diets could not achieve the Recommended Nutrient Intake (RNI) for thiamin, riboflavin, niacin, folate, vitamin B-12, calcium, iron, and zinc (range: 14-91% of RNI in the optimal diets) and that none of the formulated CF products could cover the nutrient gaps for thiamin, niacin, iron, and folate (range: 22-86% of the RNI). Iron was the key limiting nutrient, for all modeled diets, achieving a maximum of only 48% of the RNI when CSB++ was included in the diet. Only WF and WF-L filled the nutrient gap for calcium. WF-L, CSB+, and CSB++ filled the nutrient gap for zinc (9- to 11-mo-olds). The formulated CF products improved the nutrient adequacy of complementary feeding diets but could not entirely cover the nutrient gaps. These results emphasize the value of using LP to evaluate special CF products during the intervention planning phase. The WF study was registered at controlled-trials.com as ISRCTN19918531.

Drug discovery in prostate cancer mouse models.

PubMed

Valkenburg, Kenneth C; Pienta, Kenneth J

2015-01-01

The mouse is an important, though imperfect, organism with which to model human disease and to discover and test novel drugs in a preclinical setting. Many experimental strategies have been used to discover new biological and molecular targets in the mouse, with the hopes of translating these discoveries into novel drugs to treat prostate cancer in humans. Modeling prostate cancer in the mouse, however, has been challenging, and often drugs that work in mice have failed in human trials. The authors discuss the similarities and differences between mice and men; the types of mouse models that exist to model prostate cancer; practical questions one must ask when using a mouse as a model; and potential reasons that drugs do not often translate to humans. They also discuss the current value in using mouse models for drug discovery to treat prostate cancer and what needs are still unmet in field. With proper planning and following practical guidelines by the researcher, the mouse is a powerful experimental tool. The field lacks genetically engineered metastatic models, and xenograft models do not allow for the study of the immune system during the metastatic process. There remain several important limitations to discovering and testing novel drugs in mice for eventual human use, but these can often be overcome. Overall, mouse modeling is an essential part of prostate cancer research and drug discovery. Emerging technologies and better and ever-increasing forms of communication are moving the field in a hopeful direction.

AUI&GIV: Recommendation with Asymmetric User Influence and Global Importance Value.

PubMed

Zhao, Zhi-Lin; Wang, Chang-Dong; Lai, Jian-Huang

2016-01-01

The user-based collaborative filtering (CF) algorithm is one of the most popular approaches for making recommendation. Despite its success, the traditional user-based CF algorithm suffers one serious problem that it only measures the influence between two users based on their symmetric similarities calculated by their consumption histories. It means that, for a pair of users, the influences on each other are the same, which however may not be true. Intuitively, an expert may have an impact on a novice user but a novice user may not affect an expert at all. Besides, each user may possess a global importance factor that affects his/her influence to the remaining users. To this end, in this paper, we propose an asymmetric user influence model to measure the directed influence between two users and adopt the PageRank algorithm to calculate the global importance value of each user. And then the directed influence values and the global importance values are integrated to deduce the final influence values between two users. Finally, we use the final influence values to improve the performance of the traditional user-based CF algorithm. Extensive experiments have been conducted, the results of which have confirmed that both the asymmetric user influence model and global importance value play key roles in improving recommendation accuracy, and hence the proposed method significantly outperforms the existing recommendation algorithms, in particular the user-based CF algorithm on the datasets of high rating density.

AUI&GIV: Recommendation with Asymmetric User Influence and Global Importance Value

PubMed Central

Zhao, Zhi-Lin; Wang, Chang-Dong; Lai, Jian-Huang

2016-01-01

The user-based collaborative filtering (CF) algorithm is one of the most popular approaches for making recommendation. Despite its success, the traditional user-based CF algorithm suffers one serious problem that it only measures the influence between two users based on their symmetric similarities calculated by their consumption histories. It means that, for a pair of users, the influences on each other are the same, which however may not be true. Intuitively, an expert may have an impact on a novice user but a novice user may not affect an expert at all. Besides, each user may possess a global importance factor that affects his/her influence to the remaining users. To this end, in this paper, we propose an asymmetric user influence model to measure the directed influence between two users and adopt the PageRank algorithm to calculate the global importance value of each user. And then the directed influence values and the global importance values are integrated to deduce the final influence values between two users. Finally, we use the final influence values to improve the performance of the traditional user-based CF algorithm. Extensive experiments have been conducted, the results of which have confirmed that both the asymmetric user influence model and global importance value play key roles in improving recommendation accuracy, and hence the proposed method significantly outperforms the existing recommendation algorithms, in particular the user-based CF algorithm on the datasets of high rating density. PMID:26828803

Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts

PubMed Central

Markes, Alexander R.; Okundaye, Amenawon O.; Qu, Zhilin; Mende, Ulrike; Choi, Bum-Rak

2018-01-01

Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair. PMID:29715271

Pre-treatment of synthetic elastomeric scaffolds by cardiac fibroblasts improves engineered heart tissue

PubMed Central

Radisic, Milica; Park, Hyoungshin; Martens, Timothy P.; Salazar-Lazaro, Johanna E.; Geng, Wenliang; Wang, Yadong; Langer, Robert; Freed, Lisa E.; Vunjak-Novakovic, Gordana

2009-01-01

Native myocardium consists of several cell types, of which approximately one-third are myocytes and most of the nonmyocytes are fibroblasts. By analogy with monolayer culture in which fibroblasts were removed to prevent overgrowth, early attempts to engineer myocardium utilized cell populations enriched for cardiac myocytes (CMs; ~80–90% of total cells). We hypothesized that the pre-treatment of synthetic elastomeric scaffolds with cardiac fibroblasts (CFs) will enhance the functional assembly of the engineered cardiac constructs by creating an environment supportive of cardiomyocyte attachment and function. Cells isolated from neonatal rat ventricles were prepared to form three distinct populations: rapidly plating cells identified as CFs, slowly plating cells identified as CMs, and unseparated initial population of cells (US). The cell fractions (3 × 106 cells total) were seeded into poly(glycerol sebacate) scaffolds (highly porous discs, 5 mm in diameter × 2-mm thick) using Matrigel™, either separately (CM or CF), concurrently (US), or sequentially (CF pre-treatment followed by CM culture, CF + CM), and cultured in spinner flasks. The CF + CM group had the highest amplitude of contraction and the lowest excitation threshold, superior DNA content, and higher glucose consumption rate. The CF + CM group exhibited compact 100- to 200-μm thick layers of elongated myocytes aligned in parallel over layers of collagen-producing fibroblasts, while US and CM groups exhibited scattered and poorly elongated myocytes. The sequential co-culture of CF and CM on a synthetic elastomer scaffold thus created an environment supportive of cardiomyocyte attachment, differentiation, and contractile function, presumably due to scaffold conditioning by cultured fibroblasts. When implanted over the infarcted myocardium in a nude rat model, cell-free poly(glycerol sebacate) remained at the ventricular wall after 2 weeks of in vivo, and was vascularized. PMID:18041719

3-(imidazo[1,2-a:5,4-b']dipyridin-2-yl)aniline inhibits pestivirus replication by targeting a hot spot drug binding pocket in the RNA-dependent RNA polymerase.

PubMed

Musiu, Simone; Leyssen, Pieter; Froeyen, Mathy; Chezal, Jean-Michel; Neyts, Johan; Paeshuyse, Jan

2016-05-01

The compound 3-(imidazo[1,2-a:5,4-b']dipyridin-2-yl)aniline (CF02334) was identified as a selective inhibitor of the cytopathic effect (CPE) caused by bovine viral diarrhea virus (BVDV) in a virus-cell-based assay. The EC50-values for inhibition of CPE, viral RNA synthesis and the production of infectious virus progeny were 13.0 ± 0.6 μM, 2.6 ± 0.9 μM and 17.8 ± 0.6 μM, respectively. CF02334 was found to be inactive in the hepatitis C subgenomic replicon system. CF02334-resistant BVDV was obtained and was found to carry the N264D mutation in the viral RNA-dependent RNA polymerase (RdRp). Molecular modeling revealed that N264D is located in a small cavity near the fingertip domain of the pestivirus polymerase. CF02334-resistant BVDV was proven to be cross-resistant to BPIP, AG110 and LZ37, inhibitors that have previously been described to target the same region of the BVDV RdRp. CF02334 did not inhibit the in vitro activity of recombinant BVDV RdRp, but did inhibit the activity of BVDV replication complexes. Taken together, these observations indicate that CF02334 likely interacts with the fingertip of the pestivirus RdRp at the same position as BPIP, AG110 and LZ37, which marks this region of the viral polymerase as a "hot spot" for inhibition of pestivirus replication. Copyright © 2016 Elsevier B.V. All rights reserved.

Patients with cystic fibrosis have inducible IL-17+IL-22+ memory cells in lung draining lymph nodes.

PubMed

Chan, Yvonne R; Chen, Kong; Duncan, Steven R; Lathrop, Kira L; Latoche, Joseph D; Logar, Alison J; Pociask, Derek A; Wahlberg, Brendon J; Ray, Prabir; Ray, Anuradha; Pilewski, Joseph M; Kolls, Jay K

2013-04-01

IL-17 is an important cytokine signature of the TH differentiation pathway TH17. This T-cell subset is crucial in mediating autoimmune disease or antimicrobial immunity in animal models, but its presence and role in human disease remain to be completely characterized. We set out to determine the frequency of TH17 cells in patients with cystic fibrosis (CF), a disease in which there is recurrent infection with known pathogens. Explanted lungs from patients undergoing transplantation or organ donors (CF samples=18; non-CF, nonbronchiectatic samples=10) were collected. Hilar nodes and parenchymal lung tissue were processed and examined for TH17 signature by using immunofluorescence and quantitative real-time PCR. T cells were isolated and stimulated with antigens from Pseudomonas aeruginosa and Aspergillus species. Cytokine profiles and staining with flow cytometry were used to assess the reactivity of these cells to antigen stimulation. We found a strong IL-17 phenotype in patients with CF compared with that seen in control subjects without CF. Within this tissue, we found pathogenic antigen-responsive CD4+IL-17+ cells. There were double-positive IL-17+IL-22+ cells [TH17(22)], and the IL-22+ population had a higher proportion of memory characteristics. Antigen-specific TH17 responses were stronger in the draining lymph nodes compared with those seen in matched parenchymal lungs. Inducible proliferation of TH17(22) with memory cell characteristics is seen in the lungs of patients with CF. The function of these individual subpopulations will require further study regarding their development. T cells are likely not the exclusive producers of IL-17 and IL-22, and this will require further characterization. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Oxidation mechanisms of CF2Br2 and CH2Br2 induced by air nonthermal plasma.

PubMed

Schiorlin, Milko; Marotta, Ester; Dal Molin, Marta; Paradisi, Cristina

2013-01-02

Oxidation mechanisms in air nonthermal plasma (NTP) at room temperature and atmospheric pressure were investigated in a corona reactor energized by +dc, -dc, or +pulsed high voltage.. The two bromomethanes CF(2)Br(2) and CH(2)Br(2) were chosen as model organic pollutants because of their very different reactivities with OH radicals. Thus, they served as useful mechanistic probes: they respond differently to the presence of humidity in the air and give different products. By FT-IR analysis of the postdischarge gas the following products were detected and quantified: CO(2) and CO in the case of CH(2)Br(2), CO(2) and F(2)C ═ O in the case of CF(2)Br(2). F(2)C ═ O is a long-lived oxidation intermediate due to its low reactivity with atmospheric radicals. It is however removed from the NTP processed gas by passage through a water scrubber resulting in hydrolysis to CO(2) and HF. Other noncarbon containing products of the discharge were also monitored by FT-IR analysis, including HNO(3) and N(2)O. Ozone, an important product of air NTP, was never detected in experiments with CF(2)Br(2) and CH(2)Br(2) because of the highly efficient ozone depleting cycles catalyzed by BrOx species formed from the bromomethanes. It is concluded that, regardless of the type of corona applied, CF(2)Br(2) reacts in air NTP via a common intermediate, the CF(2)Br radical. The possible reactions leading to this radical are discussed, including, for -dc activation, charge exchange with O(2)(-), a species detected by APCI mass spectrometry.

Protective mechanism of turmeric (Curcuma longa) on carbofuran-induced hematological and hepatic toxicities in a rat model.

PubMed

Hossen, Md Sakib; Tanvir, E M; Prince, Maruf Billah; Paul, Sudip; Saha, Moumoni; Ali, Md Yousuf; Gan, Siew Hua; Khalil, Md Ibrahim; Karim, Nurul

2017-12-01

Turmeric (Curcuma longa L. [Zingiberaceae]) is used in the treatment of a variety of conditions including pesticide-induced toxicity. The study reports the antioxidant properties and the protective effects of turmeric against carbofuran (CF)-induced toxicity in rats. The antioxidant potential was determined by using free radicals scavenging activity and ferric reducing antioxidant power values. Male Wistar rats were randomly divided into four groups, designated as control, turmeric (100 mg/kg/day), CF (1 mg/kg/day) and turmeric (100 mg/kg/day) + CF (1 mg/kg/day) treatments. All of the doses were administered orally for 28 consecutive days. The biological activity of the turmeric and CF was determined by using several standard biochemical methods. Turmeric contains high concentrations of polyphenols (8.97 ± 0.15 g GAEs), flavonoids (5.46 ± 0.29 g CEs), ascorbic acid (0.06 ± 0.00 mg AEs) and FRAP value (1972.66 ± 104.78 μM Fe 2+ ) per 100 g of sample. Oral administration of CF caused significant changes in some of the blood indices, such as, mean corpuscular volume, corpuscular hemoglobin, white blood cell, platelet distribution width and induced severe hepatic injuries associated with oxidative stress, as observed by the significantly higher lipid peroxidation (LPO) levels when compared to control, while the activities of cellular antioxidant enzymes (including superoxide dismutase and glutathione peroxidase) were significantly suppressed in the liver tissue. Turmeric supplementation could protect against CF-induced hematological perturbations and hepatic injuries in rats, plausibly by the up-regulation of antioxidant enzymes and inhibition of LPO to confer the protective effect.

Chlorination-promoted skeletal transformation of IPR C76 discovered via trifluoromethylation under the formation of non-IPR C76(CF3)nFm.

PubMed

Tamm, Nadezhda B; Brotsman, Victor A; Markov, Vitaliy Yu; Kemnitz, Erhard; Troyanov, Sergey I

2018-05-22

High-temperature chlorination of an Isolated-Pentagon Rule (IPR) D2-C76 fullerene followed by high-temperature trifluoromethylation of non-IPR C76 chlorides with CF3I unexpectedly resulted in a series of non-IPR C76(CF3)nFm compounds. X-ray diffraction study with the use of synchrotron radiation revealed the mixed CF3/F structures of non-classical, non-IPR C76(CF3)14, C76(CF3)14F2, and C76(CF3)16F6.

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

Photochemistry of matrix isolated (trifluoromethyl)sulfonyl azide, CF₃SO₂N₃.

PubMed

Zeng, Xiaoqing; Beckers, Helmut; Willner, Helge; Neuhaus, Patrik; Grote, Dirk; Sander, Wolfram

2015-03-19

The photochemistry of matrix isolated (trifluoromethylsulfonyl) azide, CF3SO2N3, has been studied at low temperatures. Upon ArF laser irradiation (λ = 193 nm), the azide eliminates N2 and furnishes triplet [(trifluoromethyl)sulfonyl]nitrene, CF3SO2N, which has been characterized by IR and EPR spectroscopy. Upon subsequent UV light irradiation (λ = 260-400 nm) the nitrene converts to CF3N═SO2 and CF3S(O)NO through a Curtius-type rearrangement. Further two new species CF2N═SO2F and FSNO were identified together with CF2NF, SO2, F2CO, CF3NO, and SO as side products. In addition, triplet nitrene CF3N was detected by its EPR and IR spectra. The complex stepwise photodecomposition of matrix isolated CF3SO2N3 is discussed in terms of the observed photolysis products and quantum chemical calculations.

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.

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.

Orthology for comparative genomics in the mouse genome database.

PubMed

Dolan, Mary E; Baldarelli, Richard M; Bello, Susan M; Ni, Li; McAndrews, Monica S; Bult, Carol J; Kadin, James A; Richardson, Joel E; Ringwald, Martin; Eppig, Janan T; Blake, Judith A

2015-08-01

The mouse genome database (MGD) is the model organism database component of the mouse genome informatics system at The Jackson Laboratory. MGD is the international data resource for the laboratory mouse and facilitates the use of mice in the study of human health and disease. Since its beginnings, MGD has included comparative genomics data with a particular focus on human-mouse orthology, an essential component of the use of mouse as a model organism. Over the past 25 years, novel algorithms and addition of orthologs from other model organisms have enriched comparative genomics in MGD data, extending the use of orthology data to support the laboratory mouse as a model of human biology. Here, we describe current comparative data in MGD and review the history and refinement of orthology representation in this resource.

Highly Physical Solar Radiation Pressure Modeling During Penumbra Transitions

NASA Astrophysics Data System (ADS)

Robertson, Robert V.

Solar radiation pressure (SRP) is one of the major non-gravitational forces acting on spacecraft. Acceleration by radiation pressure depends on the radiation flux; on spacecraft shape, attitude, and mass; and on the optical properties of the spacecraft surfaces. Precise modeling of SRP is needed for dynamic satellite orbit determination, space mission design and control, and processing of data from space-based science instruments. During Earth penumbra transitions, sunlight is passing through Earth's lower atmosphere and, in the process, its path, intensity, spectral composition, and shape are significantly affected. This dissertation presents a new method for highly physical SRP modeling in Earth's penumbra called Solar radiation pressure with Oblateness and Lower Atmospheric Absorption, Refraction, and Scattering (SOLAARS). The fundamental geometry and approach mirrors past work, where the solar radiation field is modeled using a number of light rays, rather than treating the Sun as a single point source. This dissertation aims to clarify this approach, simplify its implementation, and model previously overlooked factors. The complex geometries involved in modeling penumbra solar radiation fields are described in a more intuitive and complete way to simplify implementation. Atmospheric effects due to solar radiation passing through the troposphere and stratosphere are modeled, and the results are tabulated to significantly reduce computational cost. SOLAARS includes new, more efficient and accurate approaches to modeling atmospheric effects which allow us to consider the spatial and temporal variability in lower atmospheric conditions. A new approach to modeling the influence of Earth's polar flattening draws on past work to provide a relatively simple but accurate method for this important effect. Previous penumbra SRP models tend to lie at two extremes of complexity and computational cost, and so the significant improvement in accuracy provided by the complex models has often been lost in the interest of convenience and efficiency. This dissertation presents a simple model which provides an accurate alternative to the full, high precision SOLAARS model with reduced complexity and computational cost. This simpler method is based on curve fitting to results of the full SOLAARS model and is called SOLAARS Curve Fit (SOLAARS-CF). Both the high precision SOLAARS model and the simpler SOLAARS-CF model are applied to the Gravity Recovery and Climate Experiment (GRACE) satellites. Modeling results are compared to the sub-nm/s2 precision GRACE accelerometer data and the results of a traditional penumbra SRP model. These comparisons illustrate the improved accuracy of the SOLAARS and SOLAARS-CF models. A sensitivity analyses for the GRACE orbit illustrates the significance of various input parameters and features of the SOLAARS model on results. The SOLAARS-CF model is applied to a study of penumbra SRP and the Earth flyby anomaly. Beyond the value of its results to the scientific community, this study provides an application example where the computational efficiency of the simplified SOLAARS-CF model is necessary. The Earth flyby anomaly is an open question in orbit determination which has gone unsolved for over 20 years. This study quantifies the influence of penumbra SRP modeling errors on the observed anomalies from the Galileo, Cassini, and Rosetta Earth flybys. The results of this study prove that penumbra SRP is not an explanation for or significant contributor to the Earth flyby anomaly.

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. There is very weak evidence for a shift of the genus toward a 'bubble-like' topology. To test cosmological models, we compute the genus for mock CfA surveys drawn from large (L greater than or approximately 400/h Mpc) N-body simulations of three variants of the cold dark matter (CDM) cosmogony. The genus amplitude of the 'standard' CDM model (omega h = 0.5, b = 1.5) differs from the observations (96% confidence level) on smoothing scales is less than or approximately 10/h Mpc. An open CDM model (omega h = 0.2) and a CDM model with nonzero cosmological constant (omega h = 0.24, lambda (sub 0) = 0.6) are consistent with the observed genus amplitude over the full range of smoothing scales. All of these models fail (97% confidence level) to match the broadness of the observed genus curve on smoothing scales is less than or equal to 10/h Mpc.

Stochastic Modeling of CO2 Migrations and Chemical Reactions in Deep Saline Formations

NASA Astrophysics Data System (ADS)

Ni, C.; Lee, I.; Lin, C.

2013-12-01

Carbon capture and storage (CCS) has been recognized the feasible technology that can significant reduce the anthropogenic CO2 emissions from large point sources. The CO2 injection in geological formations is one of the options to permanently store the captured CO2. Based on this concept a large number of target formations have been identified and intensively investigated with different types of techniques such as the hydrogeophysical experiments or numerical simulations. The numerical simulations of CO2 migrations in saline formations recently gather much attention because a number of models are available for this purpose and there are potential sites existing in many countries. The lower part of Cholan Formation (CF) near Changhua Coastal Industrial Park (CCIP) in west central Taiwan was identified the largest potential site for CO2 sequestration. The top elevations of the KF in this area varies from 1300 to 1700m below the sea level. Laboratory experiment showed that the permeability of CF is 10-14 to 10-12 m2. Over the years the offshore seismic survey and limited onshore borehole logs have provided information for the simulation of CO2 migration in the CF although the original investigations might not focus on the purpose of CO2 sequestration. In this study we modify the TOUGHREACT model to consider the small-scale heterogeneity in target formation and the cap rock of upper CF. A Monte Carlo Simulation (MCS) approach based on the TOUGHREACT model is employed to quantify the effect of small-scale heterogeneity on the CO2 migrations and hydrochemical reactions in the CF. We assume that the small-scale variability of permeability in KF can be described with a known Gaussian distribution. Therefore, the Gaussian type random field generator such as Sequential Gaussian Simulation (SGSIM) in Geostatistical Software Library (GSLIB) can be used to provide the random permeability realizations for the MCS. A variety of statistical parameters such as the variances and correlation lengths in a Gaussian covariance model are varied in the MCS and the uncertainty of the CO2 and other chemical concentrations are evaluated based on 144 random realizations. In this study a constant injection rate of100Mt/year supercritical CO2 is applied in the bottom of CF. The continuous injection time is 20 years and the uncertainty results are evaluated at 100 years. By comparing with the case without small-scale variability simulation results show that the CO2 plume sizes in the horizontal direction increase from tens of meters to hundreds of meters when the variances of small-scale variability are varied from 1.0 to 4.0. The changes of correlation lengths (i.e., from 100m, 200m, to 400m) show small contribution on the size increases of CO2 plumes. Other uncertainties of chemical concentrations show behaviors similar to the CO2 plume patterns.

[Research on the application of grey system theory in the pattern recognition for chromatographic fingerprints of traditional Chinese medicine].

PubMed

Wei, Hang; Lin, Li; Zhang, Yuan; Wang, Lianjing; Chen, Qinqun

2013-02-01

A model based on grey system theory was proposed for pattern recognition in chromatographic fingerprints (CF) of traditional Chinese medicine (TCM). The grey relational grade among the data series of each testing CF and the ideal CF was obtained by entropy and norm respectively, then the principle of "maximal matching degree" was introduced to make judgments, so as to achieve the purpose of variety identification and quality evaluation. A satisfactory result in the high performance liquid chromatographic (HPLC) analysis of 56 batches of different varieties of Exocarpium Citrus Grandis was achieved with this model. The errors in the chromatographic fingerprint analysis caused by traditional similarity method or grey correlation method were overcome, as the samples of Citrus grandis 'Tomentosa' and Citrus grandis (L.) Osbeck were correctly distinguished in the experiment. Furthermore in the study on the variety identification of Citrus grandis 'Tomentosa', the recognition rates were up to 92.85%, although the types and the contents of the chemical compositions of the samples were very close. At the same time, the model had the merits of low computation complexity and easy operation by computer programming. The research indicated that the grey system theory has good applicability to pattern recognition in the chromatographic fingerprints of TCM.

Clinical Model of Exercise-Related Dyspnea in Adult Patients With Cystic Fibrosis.

PubMed

Stevens, Daniel; Neyedli, Heather F

2018-05-01

Dyspnea is a highly distressing symptom of pulmonary disease that can make performing physical activities challenging. However, little is known regarding the strongest predictors of exercise-related dyspnea in adult cystic fibrosis (CF). Therefore, the purpose of the present study was to determine the best clinical model of exercise-related dyspnea in this patient group. A retrospective analysis of pulmonary function and cardiopulmonary exercise testing data from patients with CF being followed up at the Adult CF Program at St Michael's Hospital, Toronto, Canada, from 2002 to 2008 were used for the analysis. Patients (n = 88) were male 66%; aged 30.4 ± 9.4 years; body mass index (BMI) 23.1 ± 3.3 kg/m; forced expiratory volume in 1 second (FEV1) 70% ± 19% predicted; and peak oxygen uptake 74% ± 20% predicted. A multivariate linear regression model assessing the effects of age, sex, BMI, airway obstruction (FEV1), perceived muscular leg fatigue, and dynamic hyperinflation explained 54% of the variance in dyspnea severity at peak exercise (P < .01). Relative importance analysis showed that the presence of dynamic hyperinflation and perceived muscular leg fatigue were the largest contributors. Pulmonary rehabilitation programs may consider strategies to reduce dynamic hyperinflation and promote muscular function to best improve exercise-related dyspnea in this patient group.

Genetically Engineered Mouse Models for Studying Inflammatory Bowel Disease

PubMed Central

Mizoguchi, Atsushi; Takeuchi, Takahito; Himuro, Hidetomo; Okada, Toshiyuki; Mizoguchi, Emiko

2015-01-01

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that is mediated by very complex mechanisms controlled by genetic, immune, and environmental factors. More than 74 kinds of genetically engineered mouse strains have been established since 1993 for studying IBD. Although mouse models cannot fully reflect human IBD, they have provided significant contributions for not only understanding the mechanism, but also developing new therapeutic means for IBD. Indeed, 20 kinds of genetically engineered mouse models carry the susceptibility genes identified in human IBD, and the functions of some other IBD susceptibility genes have also been dissected out using mouse models. Cutting-edge technologies such as cell-specific and inducible knockout systems, which were recently employed to mouse IBD models, have further enhanced the ability of investigators to provide important and unexpected rationales for developing new therapeutic strategies for IBD. In this review article, we briefly introduce 74 kinds of genetically engineered mouse models that spontaneously develop intestinal inflammation. PMID:26387641

Comparison of the clinical and functional outcomes following 3- and 4-corner fusions.

PubMed

Singh, Harvinder P; Dias, Joseph J; Phadnis, Joideep; Bain, Gregory

2015-06-01

To explore the clinical and functional outcomes of 3-corner fusion (3CF) for stage 2 and 3 scapholunate advanced collapse and scaphoid nonunion advanced collapse. We compared the results with 4-corner fusion (4CF) using a recent published report. Twelve patients (8 men and 4 women) who had a 3CF, mean age 60 years (range, 34-75 y) were reviewed in clinic more than 1 year after surgery. Subjective outcome measures included the Michigan Hand Questionnaire and Patient Evaluation Measure. Objective outcome measures included range of motion with a flexible electrogoniometer and grip strength measured with a digital dynamometer. The results were compared using a recent report of 24 patients (17 men and 7 women) with a 4CF, mean age 55 years (range, 34-68 y) assessed with similar techniques. The patients receiving 3CF had better subjective scores with the Michigan Hand Questionnaire, including the sub-scores for activities of daily living and satisfaction. The radioulnar arc was greater after the 3CF than after the 4CF. Circumduction of the 3CF was more like a normal wrist than the 4CF. This included having faster and smoother motion, with an axis of circumduction closer to the normal wrist. Peak grip strength was similar after either a 3CF or 4CF but grip strength in the 3CF was 82% of the contralateral wrist compared with 59% for the 4CF. The 3CF provided better patient-rated scores and the arc of wrist motion was more extended, with greater ulnar deviation. Motion was smoother and more closely replicated the normal axis and functional motion of the wrist. Therapeutic III. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Sleep Phase Delay in Cystic Fibrosis: A Potential New Manifestation of Cystic Fibrosis Transmembrane Regulator Dysfunction.

PubMed

Jensen, Judy L; Jones, Christopher R; Kartsonaki, Christiana; Packer, Kristyn A; Adler, Frederick R; Liou, Theodore G

2017-08-01

Cystic fibrosis (CF) transmembrane regulator (CFTR) protein dysfunction causes CF. Improving survival allows detection of increasingly subtle disease manifestations. CFTR dysfunction in the central nervous system (CNS) may disturb circadian rhythm and thus sleep phase. We studied sleep in adults to better understand potential CNS CFTR dysfunction. We recruited participants from April 2012 through April 2015 and administered the Munich Chronotype Questionnaire (MCTQ). We compared free-day sleep measurements between CF and non-CF participants and investigated associations with CF survival predictors. We recruited 23 female and 22 male adults with CF aged 18 to 46 years and 26 female and 22 male volunteers aged 18 to 45 years. Compared with volunteers without CF, patients with CF had delayed sleep onset (0.612 h; P = .015), midsleep (1.11 h; P < .001), and wake (1.15 h; P < .001) times and prolonged sleep latency (7.21 min; P = .05) and duration (0.489 h; P = .05). Every hour delay in sleep onset was associated with shorter sleep duration by 0.29 h in patients with CF and 0.75 h in subjects without CF (P = .007) and longer sleep latency by 7.51 min in patients with CF and 1.6 min in volunteers without CF (P = .035). Among patients with CF, FEV 1 % predicted, prior acute pulmonary exacerbations, and weight were independent of all free-day sleep measurements. CF in adults is associated with marked delays in sleep phase consistent with circadian rhythm phase delays. Independence from disease characteristics predictive of survival suggests that sleep phase delay is a primary manifestation of CFTR dysfunction in the CNS. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

SU-E-T-61: A Practical Process for Fabricating Passive Scatter Proton Beam Modulation Compensation Filters Using 3D Printing

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

Zhao, T; Drzymala, R

Purpose: The purpose of this project was to devise a practical fabrication process for passive scatter proton beam compensation filters (CF) that is competitive in time, cost and effort using 3D printing. Methods: DICOM compensator filter files for a proton beam were generated by our Eclipse (Varian, Inc.) treatment planning system. The compensator thickness specifications were extracted with in-house software written in Matlab (MathWorks, Inc.) code and written to a text file which could be read by the Rhinoceros 5, computer-aided design (CAD) package (Robert McNeel and Associates), which subsequently generated a smoothed model in a STereoLithographic also known asmore » a Standard Tesselation Language file (STL). The model in the STL file was subsequently refined using Netfabb software and then converted to printing instructions using Cura. version 15.02.1. for our 3D printer. The Airwolf3D, model HD2x, fused filament fabrication (FFF) 3D printer (Airwolf3D.com) was used for our fabrication system with a print speed of 150mm per second. It can print in over 22 different plastic filament materials in a build volume of 11” x 8” x 12”. We choose ABS plastic to print the 3D model of the imprint for our CFs. Results: Prints of the CF could be performed at a print speed of 70mm per second. The time to print the 3D topology for the CF for the 14 cm diameter snout of our Mevion 250 proton accelerator was less than 3 hours. The printed model is intended to subsequently be used as a mold to imprint a molten wax cylindrical to form the compensation after cooling. The whole process should be performed for a typical 3 beam treatment plan within a day. Conclusion: Use of 3D printing is practical and can be used to print a 3D model of a CF within a few hours.« less

An (e, 2e+ ion) study of electron-impact ionization and fragmentation of tetrafluoromethane at low energies

NASA Astrophysics Data System (ADS)

Hossen, Khokon; Ren, Xueguang; Wang, Enliang; Kumar, S. V. K.; Dorn, Alexander

2018-03-01

We study ionization and fragmentation of tetrafluoromethane (CF4) molecule induced by electron impact at low energies ( E 0 = 38 and 67 eV). We use a reaction microscope combined with a pulsed photoemission electron beam for our experimental investigation. The momentum vectors of the two outgoing electrons (energies E 1, E 2) and one fragment ion are detected in triple coincidence (e, 2e+ ion). After dissociation, the fragment products observed are CF3 +, CF2 +, CF+, F+ and C+. For CF3 + and CF2 + channels, we measure the ionized orbitals binding energies, the kinetic energy (KE) of the charged fragments and the two-dimensional (2D) correlation map between binding energy (BE) and KE of the fragments. From the BE and KE spectra, we conclude which molecular orbitals contribute to particular fragmentation channels of CF4. We also measure the total ionization cross section for the formation of CF3 + and CF2 + ions as function of projectile energy. We compare our results with earlier experiments and calculations for electron-impact and photoionization. The major contribution to CF3 + formation originates from ionization of the 4t2 orbital while CF2 + is mainly formed after 3t2 orbital ionization. We also observe a weak contribution of the (4a1)-1 state for the channel CF3 +.

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.

Phospa-s-Triazines and Related Compositions of Improved Hydrolytic and Thermal Stability

NASA Technical Reports Server (NTRS)

Paciorek, K. J. L.

1996-01-01

The objective of the Program was to synthesize novel degradation inhibitors for perfluoropolyalkylether fluids and to evaluate their performance as well as that of other available inhibitors. Four novel additives: (C3F7OCF(CF3)CF2OC(CF3)2CN)((C6H5)2PN)2, (C3F7O(CF(CF3)CF2O)2C(CF3)2CN)((C6H5)2PN)2, u-(C3F7OCF(CF3)CF2OC(CF3)2CN)2((C6H5)2PN)2 and C3F7(OCF(CF3)CF2)6C6H4OP(O)(OC6H5)2 were prepared, characterized and their thermal stabilities established. The alloys studied were: 440C steel, M-50 steel, Pyrowear 675, Cronidur 30, Ti (4Al, 4Mn), and Ti (6Al, 4V). The additives and metals were evaluated in two different lots of Fomblin Z25, in Krytox 143AC and in Krytox 16256. Phosphate esters were found to be fully effective in arresting perfluoropolyaucylether fluid's degradation at temperatures up to 300 C over 24 h in the presence of alloys in oxygen. The overall rating of additives was: phosphates greater than phosphate/diester mixture greater than phosphine grater vthan or equal to phpospha-s-triazines.

Oral Corrective Feedback in Second Language Classrooms

ERIC Educational Resources Information Center

Lyster, Roy; Saito, Kazuya; Sato, Masatoshi

2013-01-01

This article reviews research on oral corrective feedback (CF) in second language (L2) classrooms. Various types of oral CF are first identified, and the results of research revealing CF frequency across instructional contexts are presented. Research on CF preferences is then reviewed, revealing a tendency for learners to prefer receiving CF more…