Science.gov

Sample records for diminish bacterial clearance

  1. Air pollution particles diminish bacterial clearance in the primed lungs of mice

    SciTech Connect

    Sigaud, Samuel; Goldsmith, Carroll-Ann W.; Zhou Hongwei; Yang Zhiping; Fedulov, Alexey; Imrich, Amy; Kobzik, Lester

    2007-08-15

    Epidemiological studies reveal increased incidence of lung infection when air pollution particle levels are increased. We postulate that one risk factor for bacterial pneumonia, prior viral infection, can prime the lung for greater deleterious effects of particles via the interferon-gamma (IFN-{gamma}) characteristic of successful host anti-viral responses. To test this postulate, we developed a mouse model in which mice were treated with {gamma}-interferon aerosol, followed by exposure to concentrated ambient particles (CAPs) collected from urban air. The mice were then infected with Streptococcus pneumoniae and the effect of these treatments on the lung's innate immune response was evaluated. The combination of IFN-{gamma} priming and CAPs exposure enhanced lung inflammation, manifest as increased polymorphonuclear granulocyte (PMN) recruitment to the lung, and elevated expression of pro-inflammatory cytokine mRNAs. Combined priming and CAPs exposure resulted in impaired pulmonary bacterial clearance, as well as increased oxidant production and diminished bacterial uptake by alveolar macrophages (AMs) and PMNs. The data suggest that priming and CAPs exposure lead to an inflamed alveolar milieu where oxidant stress causes loss of antibacterial functions in AMs and recruited PMNs. The model reported here will allow further analysis of priming and CAPs exposure on lung sensitivity to infection.

  2. Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms

    PubMed Central

    Mansilla Pareja, Maria Eugenia; Colombo, Maria I.

    2013-01-01

    Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance. PMID:24137567

  3. Impaired cytokine expression, neutrophil infiltration and bacterial clearance in response to urinary tract infection in diabetic mice

    PubMed Central

    Ozer, Ahmet; Altuntas, Cengiz Z.; Bicer, Fuat; Izgi, Kenan; Hultgren, Scott J.; Liu, Guiming; Daneshgari, Firouz

    2015-01-01

    Diabetic patients have increased susceptibility to infections, and urinary tract infections (UTI) are the most common type in women with diabetes mellitus. Knowledge of bacterial clearance effectiveness following UTI in diabetics is sparse. In this study, the effects of diabetes on bacterial clearance efficiency and components of the innate immune system in response to UTI in a murine model were investigated. Streptozotocin-induced diabetic and control female C57BL/6J mice were infected with uropathogenic Escherichia coli, and bacterial load, expression of chemokines, and neutrophil infiltration in the bladder over time were investigated. Expression levels of histone deacetylases were also measured to address a potential mechanism underlying the phenotype. Bacterial clearance during UTI was significantly prolonged in diabetic mice relative to controls. Neutrophil infiltration in bladder tissue and urine, and both mRNA and protein expression of chemokines MIP-2, KC, MCP-1 and IL-6 in bladder tissue were diminished at early time points after infection in diabetic mice relative to controls. In addition, mRNA levels of histone deacetylases 1–5 were increased in diabetic mice. This is the first study to show an association of impaired bacterial clearance in diabetic mice with suppression of UTI-induced chemokine expression and neutrophil infiltration in the bladder. PMID:25663347

  4. Impaired cytokine expression, neutrophil infiltration and bacterial clearance in response to urinary tract infection in diabetic mice.

    PubMed

    Ozer, Ahmet; Altuntas, Cengiz Z; Bicer, Fuat; Izgi, Kenan; Hultgren, Scott J; Liu, Guiming; Daneshgari, Firouz

    2015-04-01

    Diabetic patients have increased susceptibility to infections, and urinary tract infections (UTI) are the most common type in women with diabetes mellitus. Knowledge of bacterial clearance effectiveness following UTI in diabetics is sparse. In this study, the effects of diabetes on bacterial clearance efficiency and components of the innate immune system in response to UTI in a murine model were investigated. Streptozotocin-induced diabetic and control female C57BL/6J mice were infected with uropathogenic Escherichia coli, and bacterial load, expression of chemokines, and neutrophil infiltration in the bladder over time were investigated. Expression levels of histone deacetylases were also measured to address a potential mechanism underlying the phenotype. Bacterial clearance during UTI was significantly prolonged in diabetic mice relative to controls. Neutrophil infiltration in bladder tissue and urine, and both mRNA and protein expression of chemokines MIP-2, KC, MCP-1 and IL-6 in bladder tissue were diminished at early time points after infection in diabetic mice relative to controls. In addition, mRNA levels of histone deacetylases 1-5 were increased in diabetic mice. This is the first study to show an association of impaired bacterial clearance in diabetic mice with suppression of UTI-induced chemokine expression and neutrophil infiltration in the bladder. PMID:25663347

  5. Hyperglycemia impedes lung bacterial clearance in a murine model of cystic fibrosis-related diabetes

    PubMed Central

    Hunt, William R.; Zughaier, Susu M.; Guentert, Dana E.; Shenep, Melissa A.; Koval, Michael; McCarty, Nael A.

    2013-01-01

    Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity associated with cystic fibrosis (CF), impacting more than half of patients over age 30. CFRD is clinically significant, portending accelerated decline in lung function, more frequent pulmonary exacerbations, and increased mortality. Despite the profound morbidity associated with CFRD, little is known about the underlying CFRD-related pulmonary pathology. Our aim was to develop a murine model of CFRD to explore the hypothesis that elevated glucose in CFRD is associated with reduced lung bacterial clearance. A diabetic phenotype was induced in gut-corrected CF transmembrane conductance regulator (CFTR) knockout mice (CFKO) and their CFTR-expressing wild-type littermates (WT) utilizing streptozotocin. Mice were subsequently challenged with an intratracheal inoculation of Pseudomonas aeruginosa (PAO1) (75 μl of 1–5 × 106 cfu/ml) for 18 h. Bronchoalveolar lavage fluid was collected for glucose concentration and cell counts. A portion of the lung was homogenized and cultured as a measure of the remaining viable PAO1 inoculum. Diabetic mice had increased airway glucose compared with nondiabetic mice. The ability to clear bacteria from the lung was significantly reduced in diabetic WT mice and control CFKO mice. Critically, bacterial clearance by diabetic CFKO mice was significantly more diminished compared with nondiabetic CFKO mice, despite an even more robust recruitment of neutrophils to the airways. This finding that CFRD mice boast an exaggerated, but less effective, inflammatory cell response to intratracheal PAO1 challenge presents a novel and useful murine model to help identify therapeutic strategies that promote bacterial clearance in CFRD. PMID:24097557

  6. Hyperglycemia impedes lung bacterial clearance in a murine model of cystic fibrosis-related diabetes.

    PubMed

    Hunt, William R; Zughaier, Susu M; Guentert, Dana E; Shenep, Melissa A; Koval, Michael; McCarty, Nael A; Hansen, Jason M

    2014-01-01

    Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity associated with cystic fibrosis (CF), impacting more than half of patients over age 30. CFRD is clinically significant, portending accelerated decline in lung function, more frequent pulmonary exacerbations, and increased mortality. Despite the profound morbidity associated with CFRD, little is known about the underlying CFRD-related pulmonary pathology. Our aim was to develop a murine model of CFRD to explore the hypothesis that elevated glucose in CFRD is associated with reduced lung bacterial clearance. A diabetic phenotype was induced in gut-corrected CF transmembrane conductance regulator (CFTR) knockout mice (CFKO) and their CFTR-expressing wild-type littermates (WT) utilizing streptozotocin. Mice were subsequently challenged with an intratracheal inoculation of Pseudomonas aeruginosa (PAO1) (75 μl of 1-5 × 10(6) cfu/ml) for 18 h. Bronchoalveolar lavage fluid was collected for glucose concentration and cell counts. A portion of the lung was homogenized and cultured as a measure of the remaining viable PAO1 inoculum. Diabetic mice had increased airway glucose compared with nondiabetic mice. The ability to clear bacteria from the lung was significantly reduced in diabetic WT mice and control CFKO mice. Critically, bacterial clearance by diabetic CFKO mice was significantly more diminished compared with nondiabetic CFKO mice, despite an even more robust recruitment of neutrophils to the airways. This finding that CFRD mice boast an exaggerated, but less effective, inflammatory cell response to intratracheal PAO1 challenge presents a novel and useful murine model to help identify therapeutic strategies that promote bacterial clearance in CFRD. PMID:24097557

  7. Discovery of bacterial NAD⁺-dependent DNA ligase inhibitors: improvements in clearance of adenosine series.

    PubMed

    Stokes, Suzanne S; Gowravaram, Madhusudhan; Huynh, Hoan; Lu, Min; Mullen, George B; Chen, Brendan; Albert, Robert; O'Shea, Thomas J; Rooney, Michael T; Hu, Haiqing; Newman, Joseph V; Mills, Scott D

    2012-01-01

    Optimization of clearance of adenosine inhibitors of bacterial NAD(+)-dependent DNA ligase is discussed. To reduce Cytochrome P-450-mediated metabolic clearance, many strategies were explored; however, most modifications resulted in compounds with reduced antibacterial activity and/or unchanged total clearance. The alkyl side chains of the 2-cycloalkoxyadenosines were fluorinated, and compounds with moderate antibacterial activity and favorable pharmacokinetic properties in rat and dog were identified. PMID:22154350

  8. Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function

    PubMed Central

    Watson, Christa Y; Molina, Ramon M; Louzada, Andressa; Murdaugh, Kimberly M; Donaghey, Thomas C; Brain, Joseph D

    2015-01-01

    Background Zinc oxide engineered nanoparticles (ZnO ENPs) have potential as nanomedicines due to their inherent properties. Studies have described their pulmonary impact, but less is known about the consequences of ZnO ENP interactions with the liver. This study was designed to describe the effects of ZnO ENPs on the liver and Kupffer cells after intravenous (IV) administration. Materials and methods First, pharmacokinetic studies were conducted to determine the tissue distribution of neutron-activated 65ZnO ENPs post-IV injection in Wistar Han rats. Then, a noninvasive in vivo method to assess Kupffer cell phagosomal motility was employed using ferromagnetic iron particles and magnetometry. We also examined whether prior IV injection of ZnO ENPs altered Kupffer cell bactericidal activity on circulating Pseudomonas aeruginosa. Serum and liver tissues were collected to assess liver-injury biomarkers and histological changes, respectively. Results We found that the liver was the major site of initial uptake of 65ZnO ENPs. There was a time-dependent decrease in tissue levels of 65Zn in all organs examined, refecting particle dissolution. In vivo magnetometry showed a time-dependent and transient reduction in Kupffer cell phagosomal motility. Animals challenged with P. aeruginosa 24 hours post-ZnO ENP injection showed an initial (30 minutes) delay in vascular bacterial clearance. However, by 4 hours, IV-injected bacteria were cleared from the blood, liver, spleen, lungs, and kidneys. Seven days post-ZnO ENP injection, creatine phosphokinase and aspartate aminotransferase levels in serum were significantly increased. Histological evidence of hepatocyte damage and marginated neutrophils were observed in the liver. Conclusion Administration of ZnO ENPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury, but did not alter bacterial clearance from the blood or killing in the liver, spleen, lungs, or kidneys. Our data show that

  9. Increased Myeloid Cell Production and Lung Bacterial Clearance in Mice Exposed to Cigarette Smoke.

    PubMed

    Basilico, Paola; Cremona, Tiziana P; Oevermann, Anna; Piersigilli, Alessandra; Benarafa, Charaf

    2016-03-01

    Pneumonia is a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD). Although most patients with COPD are smokers, the effects of cigarette smoke exposure on clearance of lung bacterial pathogens and on immune and inflammatory responses are incompletely defined. Here, clearance of Streptococcus pneumoniae and Pseudomonas aeruginosa and associated immune responses were examined in mice exposed to cigarette smoke or after smoking cessation. Mice exposed to cigarette smoke for 6 weeks or 4 months demonstrated decreased lung bacterial burden compared with air-exposed mice when infected 16 to 24 hours after exposure. When infection was performed after smoke cessation, bacterial clearance kinetics of mice previously exposed to smoke reversed to levels comparable to those of control mice, suggesting that the observed defects were not dependent on adaptive immunological memory to bacterial determinants found in smoke. Comparing cytokine levels and myeloid cell production before infection in mice exposed to cigarette smoke with mice never exposed or after smoke cessation revealed that reduced bacterial burden was most strongly associated with higher levels of IL-1β and granulocyte-macrophage colony-stimulating factor in the lungs and with increased neutrophil reserve and monocyte turnover in the bone marrow. Using Serpinb1a-deficient mice with reduced neutrophil numbers and treatment with granulocyte colony-stimulating factor showed that increased neutrophil numbers contribute only in part to the effect of smoke on infection. Our findings indicate that cigarette smoke induces a temporary and reversible increase in clearance of lung pathogens, which correlates with local inflammation and increased myeloid cell output from the bone marrow. PMID:26273827

  10. Radiolabel ratio method for measuring pulmonary clearance of intratracheal bacterial challenges

    SciTech Connect

    LaForce, F.M.; Boose, D.S.

    1988-02-01

    Calculation of bacterial clearance is a fundamental step in any study of in situ lung antibacterial defenses. A method is described whereby about 85% of a radiolabeled bacterial inoculum was consistently introduced into the bronchopulmonary tree of a mouse by the intratracheal route. Mice were then killed 1 and 4 hours later; their lungs were removed aseptically and homogenized, and viable bacteria and radiolabel counts were determined. Radiolabel counts fell slowly, and more than 80% of the original radiolabel was still present in homogenized lung samples from animals sacrificed 4 hours after challenge. Bacteria/isotope ratios for the bacterial inoculum and homogenized lung samples from animals sacrificed immediately after challenge were very similar. Bacterial clearance values were the same whether computed from bacterial counts alone or according to a radiolabel ratio method whereby the change in the bacteria/isotope ratio in ground lung aliquots was divided by a similar ratio from bacteria used to inoculate animals. Some contamination resulted from oral streptococci being swept into the bronchopulmonary free during the aspiration process. This contamination was not a problem when penicillin was incorporated into the agar and penicillin-resistant strains were used for the bacterial challenges.

  11. A PPARγ AGONIST ENHANCES BACTERIAL CLEARANCE THROUGH NEUTROPHIL EXTRACELLULAR TRAP FORMATION AND IMPROVES SURVIVAL IN SEPSIS.

    PubMed

    Araújo, Cláudia V; Campbell, Clarissa; Gonçalves-de-Albuquerque, Cassiano F; Molinaro, Raphael; Cody, Mark J; Yost, Christian C; Bozza, Patricia T; Zimmerman, Guy A; Weyrich, Andrew S; Castro-Faria-Neto, Hugo C; Silva, Adriana R

    2016-04-01

    Dysregulation of the inflammatory response against infection contributes to mortality in sepsis. Inflammation provides critical host defense, but it can cause tissue damage, multiple organ failure, and death. Because the nuclear transcription factor peroxisome proliferator-activated receptor γ (PPARγ) exhibits therapeutic potential, we characterized the role of PPARγ in sepsis. We analyzed severity of clinical signs, survival rates, cytokine production, leukocyte influx, and bacterial clearance in a cecal ligation and puncture (CLP) model of sepsis in Swiss mice. The PPARγ agonist rosiglitazone treatment improved clinical status and mortality, while increasing IL-10 production and decreasing TNF-α and IL-6 levels, and peritoneal neutrophil accumulation 24 h after CLP. We noted increased bacterial killing in rosiglitazone treated mice, correlated with increased generation of reactive oxygen species. Polymorphonuclear leukocytes (PMN) incubated with LPS or Escherichia coli and rosiglitazone increased peritoneal neutrophil extracellular trap (NET)-mediated bacterial killing, an effect reversed by the PPARγ antagonist (GW 9662) treatment. Rosiglitazone also enhanced the release of histones by PMN, a surrogate marker of NET formation, effect abolished by GW 9662. Rosiglitazone modulated the inflammatory response and increased bacterial clearance through PPARγ activation and NET formation, combining immunomodulatory and host-dependent anti-bacterial effects and, therefore, warrants further study as a potential therapeutic agent in sepsis. PMID:26618986

  12. New heparinizable modified poly(carbonate urethane) surfaces diminishing bacterial colonization.

    PubMed

    De Nardo, Luigi; Farè, Silvia; Di Matteo, Valentina; Cipolla, Eliana; Saino, Enrica; Visai, Livia; Speziale, Pietro; Tanzi, Maria Cristina

    2007-11-01

    Percutaneous devices are extensively used in modern medicine therapies, even in long term applications. Complications from their use, related to bacterial colonization and/or to materials thrombogenicity, may result in a significant morbidity and mortality incidence. In this study, a novel polycarbonate-urethane (PCU), incorporating a tailor-made diamino-diamide-diol (PIME) showing the ability to bind heparin at physiological pH, was compared to commercial medical-grade PCUs (Carbothane and Bionate). Mechanical and thermal properties were evaluated by tensile tests, dynamic mechanical analysis and differential scanning calorimetry. The presence of a low amount of PIME chain extender in Bionate polyurethanes (Bionate-PIME) slightly affects the mechanical properties, remaining however comparable with the medical grade PCUs used for the fabrication of cardiovascular devices. To verify thereof heparin surface adsorbed in disfavouring bacterial colonization, heparinized Bionate-PIME was tested for bacterial adhesion, using Bionate and Carbothane as reference. In vitro bacterial interaction tests were performed with the strains mainly involved in the pathogenesis of device-related infections (S. epidermidis and S. aureus). MTT tests and SEM observations showed a decrease in colonization of the different strains on the heparinized Bionate-PIME surfaces, confirming that preadsorbed heparin plays a role in mediating the biomaterial surface/bacterial cells interactions. PMID:17665117

  13. Lipopolysaccharide clearance, bacterial clearance, and systemic inflammatory responses are regulated by cell type-specific functions of TLR4 during sepsis.

    PubMed

    Deng, Meihong; Scott, Melanie J; Loughran, Patricia; Gibson, Gregory; Sodhi, Chhinder; Watkins, Simon; Hackam, David; Billiar, Timothy R

    2013-05-15

    The morbidity associated with bacterial sepsis is the result of host immune responses to pathogens, which are dependent on pathogen recognition by pattern recognition receptors, such as TLR4. TLR4 is expressed on a range of cell types, yet the mechanisms by which cell-specific functions of TLR4 lead to an integrated sepsis response are poorly understood. To address this, we generated mice in which TLR4 was specifically deleted from myeloid cells (LysMTLR4KO) or hepatocytes (HCTLR4KO) and then determined survival, bacterial counts, host inflammatory responses, and organ injury in a model of cecal ligation and puncture (CLP), with or without antibiotics. LysM-TLR4 was required for phagocytosis and efficient bacterial clearance in the absence of antibiotics. Survival, the magnitude of the systemic and local inflammatory responses, and liver damage were associated with bacterial levels. HCTLR4 was required for efficient LPS clearance from the circulation, and deletion of HCTLR4 was associated with enhanced macrophage phagocytosis, lower bacterial levels, and improved survival in CLP without antibiotics. Antibiotic administration during CLP revealed an important role for hepatocyte LPS clearance in limiting sepsis-induced inflammation and organ injury. Our work defines cell type-selective roles for TLR4 in coordinating complex immune responses to bacterial sepsis and suggests that future strategies for modulating microbial molecule recognition should account for varying roles of pattern recognition receptors in multiple cell populations. PMID:23562812

  14. Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen

    PubMed Central

    Javid, Ashkan; Zlotnikov, Nataliya; Pětrošová, Helena; Tang, Tian Tian; Zhang, Yang; Bansal, Anil K.; Ebady, Rhodaba; Parikh, Maitry; Ahmed, Mijhgan; Sun, Chunxiang; Newbigging, Susan; Kim, Yae Ram; Santana Sosa, Marianna; Glogauer, Michael

    2016-01-01

    Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted. PMID:27340827

  15. Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

    PubMed

    Javid, Ashkan; Zlotnikov, Nataliya; Pětrošová, Helena; Tang, Tian Tian; Zhang, Yang; Bansal, Anil K; Ebady, Rhodaba; Parikh, Maitry; Ahmed, Mijhgan; Sun, Chunxiang; Newbigging, Susan; Kim, Yae Ram; Santana Sosa, Marianna; Glogauer, Michael; Moriarty, Tara J

    2016-01-01

    Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted. PMID:27340827

  16. Thyroid Hormone Enhances Nitric Oxide-Mediated Bacterial Clearance and Promotes Survival after Meningococcal Infection

    PubMed Central

    Wang, Xiao; Altenbacher, Georg; Hagner, Matthias; Berglund, Pernilla; Gao, Yumin; Lu, Ting; Jonsson, Ann-Beth; Sjölinder, Hong

    2012-01-01

    Euthyroid sick syndrome characterized by reduced levels of thyroid hormones (THs) is observed in patients with meningococcal shock. It has been found that the level of THs reflects disease severity and is predictive for mortality. The present study was conducted to investigate the impact of THs on host defense during meningococcal infection. We found that supplementation of thyroxine to mice infected with Neisseria meningitidis enhanced bacterial clearance, attenuated the inflammatory responses and promoted survival. In vitro studies with macrophages revealed that THs enhanced bacteria-cell interaction and intracellular killing of meningococci by stimulating inducible nitric oxide synthase (iNos)-mediated NO production. TH treatment did not activate expression of TH receptors in macrophages. Instead, the observed TH-directed actions were mediated through nongenomic pathways involving the protein kinases PI3K and ERK1/2 and initiated at the membrane receptor integrin αvβ3. Inhibition of nongenomic TH signaling prevented iNos induction, NO production and subsequent intracellular bacterial killing by macrophages. These data demonstrate a beneficial role of THs in macrophage-mediated N. meningitidis clearance. TH replacement might be a novel option to control meningococcal septicemia. PMID:22844479

  17. Activation of Pattern Recognition Receptors Upregulates Metallothioneins, Thereby Increasing Intracellular Accumulation of Zinc, Autophagy, and Bacterial Clearance by Macrophages

    PubMed Central

    Lahiri, Amit; Abraham, Clara

    2014-01-01

    Background & Aims Continuous stimulation of pattern recognition receptors (PRRs), including nucleotide-binding oligomerization domain-2 (NOD2) (variants in NOD2 have been associated with Crohn's disease), alters the phenotype of myeloid-derived cells, reducing production of inflammatory cytokines and increasing clearance of microbes. We investigated the mechanisms by which microbial clearance increases in macrophages under these conditions. METHODS Monocytes were purified from human peripheral blood mononuclear cells and differentiated to monocyte-derived macrophages (MDMs). We also isolated human intestinal macrophages. Bacterial clearance by MDMs was assessed in gentamicin protection assays. Effects of intracellular zinc and autophagy were measured by flow cytometry, immunoblot, reverse transcription PCR, and microscopy experiments. Small interfering RNAs were used to knock down specific proteins in MDMs. NOD2–/– and C57BL/6J mice, maintained in a specific pathogen-free facility, were given antibiotics, muramyl dipeptide (to stimulate NOD2), or dextran sodium sulfate; intestinal lamina propria cells were collected and analyzed. RESULTS Chronic stimulation of human MDMs through NOD2 upregulated the expression of multiple genes encoding metallothioneins, which bind and regulate levels of intracellular zinc. Intestinal myeloid-derived cells are continually stimulated through PRRs; metallothionein expression was upregulated in human and mouse intestinal myeloid-derived cells. Continuous stimulation of NOD2 increased levels of intracellular zinc, thereby increasing autophagy and bacterial clearance. The metal-regulatory transcription factor-1 (MTF-1) was required for regulation of metallothionein genes in human MDMs. Knockdown of MTF-1 did not affect baseline clearance of bacteria by MDMs. However, the increase in intracellular zinc, autophagy, and bacterial clearance observed with continuous NOD2 stimulation was impaired in MDMs upon MTF-1 knockdown. Addition of

  18. CAP-D3 Promotes Bacterial Clearance in Human Intestinal Epithelial Cells by Repressing Expression of Amino Acid Transporters

    PubMed Central

    Kemp, Jacqueline R.; Nickerson, Kourtney P.; Deutschman, Emily; Kim, Yeojung; West, Gail; Sadler, Tammy; Stylianou, Eleni; Krokowski, Dawid; Hatzoglou, Maria; de la Motte, Carol; Rubin, Brian P.; Fiocchi, Claudio

    2015-01-01

    BACKGROUND & AIMS Defects in colonic epithelial barrier defenses are associated with ulcerative colitis (UC). The proteins that regulate bacterial clearance in the colonic epithelium have not been completely identified. The chromosome-associated protein D3 (dCAP-D3), regulates responses to bacterial infection. We examined whether CAP-D3 promotes bacterial clearance in human colonic epithelium. METHODS Clearance of Salmonella or adherent-invasive Escherichia coli LF82 was assessed by gentamycin protection assays in HT-29 and Caco-2 cells expressing small hairpin RNAs against CAP-D3. We used immunoblot assays to measure levels of CAP-D3 in colonic epithelial cells from patients with UC and healthy individuals (controls). RNA sequencing identified genes activated by CAP-D3. We analyzed the roles of CAP-D3 target genes in bacterial clearance using gentamycin protection and immunofluorescence assays and studies with pharmacologic inhibitors. RESULTS CAP-D3 expression was reduced in colonic epithelial cells from patients with active UC. Reduced CAP-D3 expression decreased autophagy and impaired intracellular bacterial clearance by HT-29 and Caco-2 colonic epithelial cells. Lower levels of CAP-D3 increased transcription of genes encoding SLC7A5 and SLC3A2, whose products heterodimerize to form an amino acid transporter in HT-29 cells following bacterial infection; levels of SLC7A5–SLC3A2 were increased in tissues from patients with UC, compared with controls. Reduced CAP-D3 in HT-29 cells resulted in earlier recruitment of SLC7A5 to Salmonella-containing vacuoles, increased activity of mTORC1, and increased survival of bacteria. Inhibition of SLC7A5–SLC3A2 or mTORC1 activity rescued the bacterial clearance defects of CAP-D3– deficient cells. CONCLUSIONS CAP-D3 downregulates transcription of genes that encode amino acid transporters (SLC7A5 and SLC3A2) to promote bacterial autophagy by colon epithelial cells. Levels of CAP-D3 protein are reduced in patients with

  19. Interleukin-33 facilitates neutrophil recruitment and bacterial clearance in S. aureus-caused peritonitis.

    PubMed

    Lan, Fang; Yuan, Baohong; Liu, Tao; Luo, Xiaochun; Huang, Ping; Liu, Yunjun; Dai, Liangcheng; Yin, Hui

    2016-04-01

    Interleukin (IL)-33, a newly recognized member of IL-1 family of cytokines, plays an important role in polarizing Th2-associated immunity. Recently growing evidence indicates that IL-33 also represents a crucial mediator of antimicrobial infection. In this study, we investigated the effect of IL-33 on antibacterial response using an acute Staphylococcus aureus peritoneal infection model. Our results showed that IL-33 administration induced a rapid bacterial clearance and markedly reduced the S. aureus infection-related mortality. IL-33-treated mice displayed increased neutrophil influx into the focus of infection and higher concentrations of chemokine CXCL2 in the peritoneum than untreated mice. The beneficial effect of IL-33 priming was related to reversal of the S. aureus-induced reduction of CXCR2 expression on the surface of neutrophils. Furthermore, conditioning of neutrophils by IL-33 led to the enhancement of complement receptor 3 expression induced by S. aureus, which in turn facilitates the phagocytosis of opsonized S. aureus. Finally, neutrophils primed by IL-33 upregulated the production of reactive oxygen species and the subsequent killing activity for S. aureus. All together, these findings suggest that IL-33, through regulating multiple steps of neutrophil-mediated bactericidal function, provides a profound effect in host antimicrobial defense response. PMID:26991049

  20. Helminth-Induced Interleukin-4 Abrogates Invariant Natural Killer T Cell Activation-Associated Clearance of Bacterial Infection

    PubMed Central

    Hsieh, Yi-Ju; Fu, Chi-Ling

    2014-01-01

    Helminth infections affect 1 billion people worldwide and render these individuals susceptible to bacterial coinfection through incompletely understood mechanisms. This includes urinary tract coinfection by bacteria and Schistosoma haematobium worms, the etiologic agent of urogenital schistosomiasis. To study the mechanisms of S. haematobium-bacterial urinary tract coinfections, we combined the first tractable model of urogenital schistosomiasis with an established mouse model of bacterial urinary tract infection (UTI). A single bladder exposure to S. haematobium eggs triggers interleukin-4 (IL-4) production and makes BALB/c mice susceptible to bacterial UTI when they are otherwise resistant. Ablation of IL-4 receptor alpha (IL-4Rα) signaling restored the baseline resistance of BALB/c mice to bacterial UTI despite prior exposure to S. haematobium eggs. Interestingly, numbers of NKT cells were decreased in coexposed versus bacterially monoinfected bladders. Given that schistosome-induced, non-natural killer T (NKT) cell leukocyte infiltration may dilute NKT cell numbers in the bladders of coexposed mice without exerting a specific functional effect on these cells, we next examined NKT cell biology on a per-cell basis. Invariant NKT (iNKT) cells from coexposed mice expressed less gamma interferon (IFN-γ) per cell than did those from mice with UTI alone. Moreover, coexposure resulted in lower CD1d expression in bladder antigen-presenting cells (APC) than did bacterial UTI alone in an IL-4Rα-dependent fashion. Finally, coexposed mice were protected from prolonged bacterial infection by administration of α-galactosylceramide, an iNKT cell agonist. Our findings point to a previously unappreciated role for helminth-induced IL-4 in impairment of iNKT cell-mediated clearance of bacterial coexposure. PMID:24643536

  1. Oral application of bacterial lysate in infancy diminishes the prevalence of atopic dermatitis in children at risk for atopy.

    PubMed

    Lau, S

    2014-06-01

    Numerous interventions such as avoidance of food allergens, prolonged breast feeding and supplementation of pro-and/or prebiotics have been tried as primary prevention of atopic dermatitis. Recent data suggest that prevention of infantile eczema is possible in a subgroup of children by feeding bacterial lysates early in life. Bacterial lysates of Escherichia coli and Enterococcus faecalis were found to impair allergic immune responses in rats. An interventional trial in 606 infants at risk for atopy showed a reduction of atopic dermatitis at the end of the treatment phase (month 2 until month 7) of 50% in a subgroup of children with single heredity for atopy. This was even more pronounced in the group of children with paternal heredity for atopy. This effect was still seen at age 1 year. There was no effect on food sensitisation. In conclusion, an immune modulation in terms of prevention of atopic dermatitis in infancy if single atopic family history is present seems to be possible by feeding bacterial lysates early in life. PMID:23886978

  2. Bacterial clearance is improved in septic mice by platelet-activating factor-acetylhydrolase (PAF-AH) administration.

    PubMed

    Teixeira-da-Cunha, Mariana G A; Gomes, Rachel N; Roehrs, Nathassia; Bozza, Fernando A; Prescott, Stephen M; Stafforini, Diana; Zimmerman, Guy A; Bozza, Patricia T; Castro-Faria-Neto, Hugo C

    2013-01-01

    Current evidence indicates that dysregulation of the host inflammatory response to infectious agents is central to the mortality of patients with sepsis. Strategies to block inflammatory mediators such as PAF have been investigated as adjuvant therapies for sepsis. PAF-AH, the enzyme responsible for PAF degradation, showed positive results in pre-clinical studies and phase II clinical trials, but the results of a phase III study were disappointing. In this study, we investigated the potential protective mechanism of PAF-AH in sepsis using the murine model of cecal ligation and puncture (CLP). Treatment with rPAF-AH increased peritoneal fluid levels of the anti-inflammatory mediators MCP-1/CCL2 after CLP. The numbers of bacteria (CFU) in the peritoneal cavity were decreased in the rPAF-AH-treated group, indicating more efficient bacterial clearance after rPAF-AH treatment. Interestingly, we observed increased levels of nitric oxide (NO) after PAF-AH administration, and rPAF-AH treatment did not decrease CFU numbers either in iNOS-deficient mice or in CCR2-deficient mice. We concluded that administration of exogenous rPAF-AH reduced inflammatory injury, altered cytokine levels and favored bacterial clearance with a clear impact on mortality through modulation of MCP-1/CCL2 and NO levels in a clinically relevant sepsis model. PMID:24069320

  3. Bone Marrow–Derived Mesenchymal Stem Cells Enhance Bacterial Clearance and Preserve Bioprosthetic Integrity in a Model of Mesh Infection

    PubMed Central

    Criman, Erik T.; Kurata, Wendy E.; Matsumoto, Karen W.; Aubin, Harry T.; Campbell, Carmen E.

    2016-01-01

    Background: The reported incidence of mesh infection in contaminated operative fields is as high as 30% regardless of the material used. Recently, mesenchymal stem cells (MSCs) have been shown to possess favorable immunomodulatory properties and improve tissue incorporation when seeded onto bioprosthetics. The aim of this study was to evaluate whether seeding noncrosslinked bovine pericardium (Veritas Collagen Matrix) with allogeneic bone marrow–derived MSCs improves infection resistance in vivo after inoculation with Escherichia coli (E. coli). Methods: Rat bone marrow–derived MSCs at passage 3 were seeded onto bovine pericardium and cultured for 7 days before implantation. Additional rats (n = 24) were implanted subcutaneously with MSC-seeded or unseeded mesh and inoculated with 7 × 105 colony-forming units of E. coli or saline before wound closure (group 1, unseeded mesh/saline; group 2, unseeded mesh/E. coli; group 3, MSC-seeded mesh/E. coli; 8 rats per group). Meshes were explanted at 4 weeks and underwent microbiologic and histologic analyses. Results: MSC-seeded meshes inoculated with E. coli demonstrated superior bacterial clearance and preservation of mesh integrity compared with E. coli–inoculated unseeded meshes (87.5% versus 0% clearance; p = 0.001). Complete mesh degradation concurrent with abscess formation was observed in 100% of rats in the unseeded/E. coli group, which is in contrast to 12.5% of rats in the MSC-seeded/E. coli group. Histologic evaluation determined that remodeling characteristics of E. coli–inoculated MSC-seeded meshes were similar to those of uninfected meshes 4 weeks after implantation. Conclusions: Augmenting a bioprosthetic material with stem cells seems to markedly enhance resistance to bacterial infection in vivo and preserve mesh integrity. PMID:27482490

  4. Critical roles of sea cucumber C-type lectin in non-self recognition and bacterial clearance.

    PubMed

    Wei, Xiumei; Liu, Xiangquan; Yang, Jianmin; Wang, Sheng; Sun, Guohua; Yang, Jialong

    2015-08-01

    C-type lectin is one important pattern recognition receptor (PRR) that plays crucial roles in multiple immune responses. A C-type lectin from sea cucumber Apostichopus japonicus (AjCTL-1) was characterized in the present study. The amino acid sequence of AjCTL-1 shared high similarities with other C-type lectins from invertebrates and vertebrates. The C-type lectin domain (CTLD) of AjCTL-1 contained a Ca(2+)-binding site 2 and four conserved cysteine residues. AjCTL-1 mRNA expression patterns in tissues and after bacterial challenge were then analysed. Quantitative PCR revealed that AjCTL-1 mRNA was widely expressed in the tested tissues of healthy sea cucumber. The highest expression level occurred in gonad followed by body wall, coelomocytes, tentacle, intestinum and longitudinal muscle, and the lowest expression level was in respiratory tree. AjCTL-1 mRNA expression in coelomocytes was significantly induced by gram-negative Listonella anguillarum and gram-positive Micrococcus luteus, with different up-regulation patterns post-challenge. Recombinant AjCTL-1 exhibited the ability to bind peptidoglycan directly, agglutinate M. luteus, Staphylococcus aureus and Escherichia coli, in a Ca(2+)-dependant manner, and enhance the phagocytosis of coelomocytes against E. coli in vitro. The results indicated that AjCTL-1 could act as a PRR in Apostichopus japonicus and had critical roles in non-self recognition and bacterial clearance against invading microbes. PMID:26052017

  5. Hindlimb Suspension and SPE-Like Radiation Impairs Clearance of Bacterial Infections

    PubMed Central

    Li, Minghong; Holmes, Veronica; Zhou, Yu; Ni, Houping; Sanzari, Jenine K.; Kennedy, Ann R.; Weissman, Drew

    2014-01-01

    A major risk of extended space travel is the combined effects of weightlessness and radiation exposure on the immune system. In this study, we used the hindlimb suspension model of microgravity that includes the other space stressors, situational and confinement stress and alterations in food intake, and solar particle event (SPE)-like radiation to measure the combined effects on the ability to control bacterial infections. A massive increase in morbidity and decrease in the ability to control bacterial growth was observed using 2 different types of bacteria delivered by systemic and pulmonary routes in 3 different strains of mice. These data suggest that an astronaut exposed to a strong SPE during extended space travel is at increased risk for the development of infections that could potentially be severe and interfere with mission success and astronaut health. PMID:24454913

  6. miR-155 suppresses bacterial clearance in Pseudomonas aeruginosa-induced keratitis by targeting Rheb.

    PubMed

    Yang, Kun; Wu, Minhao; Li, Meiyu; Li, Dandan; Peng, Anping; Nie, Xinxin; Sun, Mingxia; Wang, Jinli; Wu, Yongjian; Deng, Qiuchan; Zhu, Min; Chen, Kang; Yuan, Jin; Huang, Xi

    2014-07-01

    miR-155 (microRNA-155) is an important noncoding RNA in regulating host inflammatory responses. However, its regulatory role in ocular infection remains unclear. Our study first explored the function of miR-155 in Pseudomonas aeruginosa-induced keratitis, one of the most common sight-threatening ocular diseases. We found that miR-155 expression was enhanced in human and mouse corneas after P. aeruginosa infection and was mainly expressed in macrophages but not neutrophils. In vivo studies demonstrated that miR-155 knockout mice displayed more resistance to P. aeruginosa keratitis, with a higher inducible nitric oxide synthase level and a lower bacterial burden. More importantly, in vitro data indicated that miR-155 suppressed the macrophage-mediated bacterial phagocytosis and intracellular killing of P. aeruginosa by targeting Rheb (Ras homolog enriched in brain). To the best of our knowledge, this is the first study to explore the role of miR-155 in bacterial keratitis, which may provide a promising target for clinical treatment of P. aeruginosa keratitis and other infectious diseases. PMID:24403554

  7. Intermittent fasting promotes bacterial clearance and intestinal IgA production in Salmonella typhimurium-infected mice.

    PubMed

    Godínez-Victoria, M; Campos-Rodriguez, R; Rivera-Aguilar, V; Lara-Padilla, E; Pacheco-Yepez, J; Jarillo-Luna, R A; Drago-Serrano, M E

    2014-05-01

    The impact of intermittent fasting versus ad libitum feeding during Salmonella typhimurium infection was evaluated in terms of duodenum IgA levels, bacterial clearance and intestinal and extra-intestinal infection susceptibility. Mice that were intermittently fasted for 12 weeks or fed ad libitum were infected with S. typhimurium and assessed at 7 and 14 days post-infection. Next, we evaluated bacterial load in the faeces, Peyer's patches, spleen and liver by plate counting, as well as total and specific intestinal IgA and plasmatic corticosterone levels (by immunoenzymatic assay) and lamina propria IgA levels in plasma cells (by cytofluorometry). Polymeric immunoglobulin receptor, α- and J-chains, Pax-5 factor, pro-inflammatory cytokine (tumour necrosis factor-α and interferon-γ) and anti-inflammatory cytokine (transforming growth factor-β) mRNA levels were assessed in mucosal and liver samples (by real-time PCR). Compared with the infected ad libitum mice, the intermittently fasted infected animals had (1) lower intestinal and systemic bacterial loads; (2) higher SIgA and IgA plasma cell levels; (3) higher mRNA expression of most intestinal parameters; and (4) increased or decreased corticosterone levels on day 7 and 14 post-infection, respectively. No contribution of liver IgA was observed at the intestinal level. Apparently, the changes following metabolic stress induced by intermittent fasting during food deprivation days increased the resistance to S. typhimurium infection by triggering intestinal IgA production and presumably, pathogen elimination by phagocytic inflammatory cells. PMID:24612255

  8. Resolvin D4 stereoassignment and its novel actions in host protection and bacterial clearance

    PubMed Central

    Winkler, Jeremy W.; Orr, Sarah K.; Dalli, Jesmond; Cheng, Chien-Yee C.; Sanger, Julia M.; Chiang, Nan; Petasis, Nicos A.; Serhan, Charles N.

    2016-01-01

    Resolvins of the D-series are specialized pro-resolving lipid mediators that regulate cellular response by orchestrating resolution networks involved in host responses to injury and infection. Here, endogenous resolvin D4 was identified in human tissues and found to persist late into the resolution phase of acute murine Staphylococcus aureus infections. Completion of the first total synthesis of resolvin D4 established the absolute stereochemical configuration of RvD4 confirmed by matching with endogenous RvD4 from resolving exudates in dorsal pouch S. aureus infections. In vivo, RvD4 (ng/mouse) reduced neutrophilic infiltration (~40%) and enhanced uptake of apoptotic PMN (51%) by human dermal fibroblasts at concentrations as low as 0.1 nM. These results establish the complete stereochemistry of RvD4 as 4S,5R,17S-trihydroxydocosa-6E,8E,10Z,13Z,15E,19Z-hexaenoic acid and its novel pro-resolving actions in S. aureus infections as well as its potent ability to stimulate clearance of apoptotic cells by skin fibroblasts. PMID:26743932

  9. Low-Dose Oxygen Enhances Macrophage-Derived Bacterial Clearance following Cigarette Smoke Exposure

    PubMed Central

    Bain, William G.; Tripathi, Ashutosh; Mandke, Pooja; Gans, Jonathan H.; D'Alessio, Franco R.; Sidhaye, Venkataramana K.; Aggarwal, Neil R.

    2016-01-01

    Background. Chronic obstructive pulmonary disease (COPD) is a common, smoking-related lung disease. Patients with COPD frequently suffer disease exacerbations induced by bacterial respiratory infections, suggestive of impaired innate immunity. Low-dose oxygen is a mainstay of therapy during COPD exacerbations; yet we understand little about whether oxygen can modulate the effects of cigarette smoke on lung immunity. Methods. Wild-type mice were exposed to cigarette smoke for 5 weeks, followed by intratracheal instillation of Pseudomonas aeruginosa (PAO1) and 21% or 35–40% oxygen. After two days, lungs were harvested for PAO1 CFUs, and bronchoalveolar fluid was sampled for inflammatory markers. In culture, macrophages were exposed to cigarette smoke and oxygen (40%) for 24 hours and then incubated with PAO1, followed by quantification of bacterial phagocytosis and inflammatory markers. Results. Mice exposed to 35–40% oxygen after cigarette smoke and PAO1 had improved survival and reduced lung CFUs and inflammation. Macrophages from these mice expressed less TNF-α and more scavenger receptors. In culture, macrophages exposed to cigarette smoke and oxygen also demonstrated decreased TNF-α secretion and enhanced phagocytosis of PAO1 bacteria. Conclusions. Our findings demonstrate a novel, protective role for low-dose oxygen following cigarette smoke and bacteria exposure that may be mediated by enhanced macrophage phagocytosis. PMID:27403445

  10. Increased surfactant protein D fails to improve bacterial clearance and inflammation in serpinB1-/- mice.

    PubMed

    Stolley, J Michael; Gong, Dapeng; Farley, Kalamo; Zhao, Picheng; Cooley, Jessica; Crouch, Erika C; Benarafa, Charaf; Remold-O'Donnell, Eileen

    2012-12-01

    Previously, we described the protective role of the neutrophil serine protease inhibitor serpinB1 in preventing early mortality of Pseudomonas aeruginosa lung infection by fostering bacterial clearance and limiting inflammatory cytokines and proteolytic damage. Surfactant protein D (SP-D), which maintains the antiinflammatory pulmonary environment and mediates bacterial removal, was degraded in infected serpinB1-deficient mice. Based on the hypothesis that increased SP-D would rescue or mitigate the pathological effects of serpinB1 deletion, we generated two serpinB1(-/-) lines overexpressing lung-specific rat SP-D and inoculated the mice with P. aeruginosa. Contrary to predictions, bacterial counts in the lungs of SP-D(low)serpinB1(-/-) and SP-D(high) serpinB1(-/-) mice were 4 logs higher than wild-type and not different from serpinB1(-/-) mice. SP-D overexpression also failed to mitigate inflammation (TNF-α), lung injury (free protein, albumin), or excess neutrophil death (free myeloperoxidase, elastase). These pathological markers were higher for infected SP-D(high)serpinB1(-/-) mice than for serpinB1(-/-) mice, although the differences were not significant after controlling for multiple comparisons. The failure of transgenic SP-D to rescue antibacterial defense of serpinB1-deficient mice occurred despite 5-fold or 20-fold increased expression levels, largely normal structure, and dose-dependent bacteria-aggregating activity. SP-D of infected wild-type mice was intact in 43-kD monomers by reducing SDS-PAGE. By contrast, proteolytic fragments of 35, 17, and 8 kD were found in infected SP-D(low)serpinB1(-/-), SP-D(high) serpinB1(-/-) mice, and serpinB1(-/-) mice. Thus, although therapies to increase lung concentration of SP-D may have beneficial applications, the findings suggest that therapy with SP-D may not be beneficial for lung inflammation or infection if the underlying clinical condition includes excess proteolysis. PMID:23024061

  11. Cigarette Smoke Exposure Impairs Pulmonary Bacterial Clearance and Alveolar Macrophage Complement-Mediated Phagocytosis of Streptococcus pneumoniae▿

    PubMed Central

    Phipps, John C.; Aronoff, David M.; Curtis, Jeffrey L.; Goel, Deepti; O'Brien, Edmund; Mancuso, Peter

    2010-01-01

    Cigarette smoke exposure increases the risk of pulmonary and invasive infections caused by Streptococcus pneumoniae, the most commonly isolated organism from patients with community-acquired pneumonia. Despite this association, the mechanisms by which cigarette smoke exposure diminishes host defense against S. pneumoniae infections are poorly understood. In this study, we compared the responses of BALB/c mice following an intratracheal challenge with S. pneumoniae after 5 weeks of exposure to room air or cigarette smoke in a whole-body exposure chamber in vivo and the effects of cigarette smoke on alveolar macrophage phagocytosis of S. pneumoniae in vitro. Bacterial burdens in cigarette smoke-exposed mice were increased at 24 and 48 h postinfection, and this was accompanied by a more pronounced clinical appearance of illness, hypothermia, and increased lung homogenate cytokines interleukin-1β (IL-1β), IL-6, IL-10, and tumor necrosis factor alpha (TNF-α). We also found greater numbers of neutrophils in bronchoalveolar lavage fluid recovered from cigarette smoke-exposed mice following a challenge with heat-killed S. pneumoniae. Interestingly, overnight culture of alveolar macrophages with 1% cigarette smoke extract, a level that did not affect alveolar macrophage viability, reduced complement-mediated phagocytosis of S. pneumoniae, while the ingestion of unopsonized bacteria or IgG-coated microspheres was not affected. This murine model provides robust additional support to the hypothesis that cigarette smoke exposure increases the risk of pneumococcal pneumonia and defines a novel cellular mechanism to help explain this immunosuppressive effect. PMID:20008540

  12. Mucosal immunisation with novel Streptococcus pneumoniae protein antigens enhances bacterial clearance in an acute mouse lung infection model.

    PubMed

    Jomaa, Maha; Kyd, Jennelle M; Cripps, Allan W

    2005-04-01

    Streptococcus pneumoniae contains many proteins that have not been evaluated as potential protective vaccine antigens. In this study we isolated proteins from a serotype 3 strain of S. pneumoniae for use in mouse immunisation studies. Separation of the protein mix was achieved by SDS-PAGE electrophoresis followed by electro-elution to isolate individual proteins. This procedure successfully separated 21 fractions from which six proteins were selected based on purity and quantity and were initially denoted by their molecular masses: 14-, 34-, 38-, 48-, 57- and 75-kDa. The immunogenicity of these proteins was investigated in a mucosal immunisation model in mice involving a primary inoculation to the intestinal Peyer's patches followed by an intra-tracheal boost two weeks later. The immune response was assessed by enhancement of pulmonary clearance of infection, recruitment of phagocytes to the lungs and induction of an antibody response. Two of the proteins, the 14-kDa identified as a L7/L12 ribosomal protein, and the 34-kDa identified as glyceraldehyde-3-phosphate dehydrogenase resulted in up to 99% and 94%, respectively, enhanced clearance of infection within 5 h following pulmonary challenge with S. pneumoniae. This study has shown that novel pneumococcal proteins have the potential to be vaccine candidates to enhance clearance of an acute mucosal S. pneumoniae infection. PMID:15780579

  13. Disorders of diminished motivation.

    PubMed

    Marin, Robert S; Wilkosz, Patricia A

    2005-01-01

    Disorders of diminished motivation occur frequently in individuals with traumatic brain injury. Motivation is an ever-present, essential determinant of behavior and adaptation. The major syndromes of diminished motivation are apathy, abulia, and akinetic mutism. Depending on their etiology, disorders of diminished motivation may be a primary clinical disturbance, a symptom of another disorder, or a coexisting second disorder. This article presents a biopsychosocial approach to the assessment and management of motivational impairments in patients with traumatic brain injury. The recognition and differential diagnosis of disorders of diminished motivation, as well as the mechanism and clinical pathogenesis, are discussed. PMID:16030444

  14. In vivo study on the immunomodulating effects of OM-85 BV on survival, inflammatory cell recruitment and bacterial clearance in Klebsiella pneumonia.

    PubMed

    Broug-Holub, E; Kraal, G

    1997-01-01

    Oral administration of the bacterial extract OM-85 BV has been shown to prime alveolar macrophages (AM) in such a way that they secrete significantly more nitric oxide, tumor necrosis factor-alpha and interleukin-1beta upon in vitro stimulation with lipopolysaccharide (LPS). As increased cytokine secretion by AM may account for the therapeutic effect of OM-85 BV in respiratory tract infections, we studied the effect of orally administered OM-85 BV on the outcome of Klebsiella pneumoniae-induced pneumonia. Mice received a daily oral dose of OM-85 BV (350 mg/kg body weight) for 5 days and were intratracheally infected with 333, 1000 or 3333 CFU K. pneumoniae on day 8. It was shown that OM-85 BV pretreatment of mice has no effect on bacterial clearance, neutrophil recruitment and survival in this acute respiratory tract infection. Also, OM-85 BV treatment had no protective effect in a recurrent infection with K. pneumoniae. It is concluded that AM activation by oral treatment with OM-85 BV is not sufficient to play a protective role in respiratory tract infection with K. pneumoniae. PMID:9637354

  15. The Diminishing Apple.

    ERIC Educational Resources Information Center

    Kelly, Catherine

    2002-01-01

    Introduces the Apple Ocean activity which teaches about the diminishing natural resources of the earth including drinkable water, habitable land, and productive areas while working with fractions, ratios, and proportions. (YDS)

  16. Nucleation of platelets with bloodborne pathogens on Kupffer cell precedes other innate immunity and contributes to bacterial clearance

    PubMed Central

    Wong, Connie H. Y.; Jenne, Craig N.; Petri, Björn; Chrobok, Navina L.; Kubes, Paul

    2016-01-01

    Using intravital imaging of the liver, we unveil a collaborative role for platelets with Kupffer cells (KCs) in eradicating bloodborne bacterial infections. Under basal conditions, platelets via glycoprotein Ib (GPIb) formed transient “touch-and-go” interactions with von Willebrand factor (vWF) constitutively expressed on KCs. Bacteria, such as Bacillus cereus and Methicillin-resistant Staphylococcus aureus (MRSA), were rapidly caught by KCs and triggered platelets to switch from “touch-and-go” to sustained GPIIb-mediated adhesion on the KC surface to encase the bacterium. Infected GpIbα−/− mice demonstrated increased endothelial and KC damage, leading to increased fluid leakage, significant polycythemia and rapid mortality. This study identifies a novel surveillance mechanism of intravascular macrophage by platelets that rapidly converts to a critical host response against bloodborne bacteria. PMID:23770641

  17. Vaccination with Brucella abortus recombinant in vivo-induced antigens reduces bacterial load and promotes clearance in a mouse model for infection.

    PubMed

    Lowry, Jake E; Isaak, Dale D; Leonhardt, Jack A; Vernati, Giulia; Pate, Jessie C; Andrews, Gerard P

    2011-01-01

    Current vaccines used for the prevention of brucellosis are ineffective in inducing protective immunity in animals that are chronically infected with Brucella abortus, such as elk. Using a gene discovery approach, in vivo-induced antigen technology (IVIAT) on B. abortus, we previously identified ten loci that encode products up-regulated during infection in elk and consequently may play a role in virulence. In our present study, five of the loci (D15, 0187, VirJ, Mdh, AfuA) were selected for further characterization and compared with three additional antigens with virulence potential (Hia, PrpA, MltA). All eight genes were PCR-amplified from B. abortus and cloned into E. coli. The recombinant products were then expressed, purified, adjuvanted, and delivered subcutaneously to BALB/c mice. After primary immunization and two boosts, mice were challenged i.p. with 5 x 10⁴ CFU of B. abortus strain 19. Spleens from challenged animals were harvested and bacterial loads determined by colony count at various time points. While vaccination with four of the eight individual proteins appeared to have some effect on clearance kinetics, mice vaccinated with recombinant Mdh displayed the most significant reduction in bacterial colonization. Furthermore, mice immunized with Mdh maintained higher levels of IFN-γ in spleens compared to other treatment groups. Collectively, our in vivo data gathered from the S19 murine colonization model suggest that vaccination with at least three of the IVIAT antigens conferred an enhanced ability of the host to respond to infection, reinforcing the utility of this methodology for the identification of potential vaccine candidates against brucellosis. Mechanisms for immunity to one protein, Mdh, require further in vitro exploration and evaluation against wild-type B. abortus challenge in mice, as well as other hosts. Additional studies are being undertaken to clarify the role of Mdh and other IVI antigens in B. abortus virulence and induction of

  18. Reduced Bacterial Colony Count of Anaerobic Bacteria Is Associated with a Worsening in Lung Clearance Index and Inflammation in Cystic Fibrosis

    PubMed Central

    Bradley, Judy M.; Johnston, Elinor; McGrath, Stephanie; McIlreavey, Leanne; Rowan, Stephen; Reid, Alastair; Bradbury, Ian; Einarsson, Gisli

    2015-01-01

    Anaerobic bacteria have been identified in abundance in the airways of cystic fibrosis (CF) subjects. The impact their presence and abundance has on lung function and inflammation is unclear. The aim of this study was to investigate the relationship between the colony count of aerobic and anaerobic bacteria, lung clearance index (LCI), spirometry and C-Reactive Protein (CRP) in patients with CF. Sputum and blood were collected from CF patients at a single cross-sectional visit when clinically stable. Community composition and bacterial colony counts were analysed using extended aerobic and anaerobic culture. Patients completed spirometry and a multiple breath washout (MBW) test to obtain LCI. An inverse correlation between colony count of aerobic bacteria (n = 41, r = -0.35; p = 0.02), anaerobic bacteria (n = 41, r = -0.44, p = 0.004) and LCI was observed. There was an inverse correlation between colony count of anaerobic bacteria and CRP (n = 25, r = -0.44, p = 0.03) only. The results of this study demonstrate that a lower colony count of aerobic and anaerobic bacteria correlated with a worse LCI. A lower colony count of anaerobic bacteria also correlated with higher CRP levels. These results indicate that lower abundance of aerobic and anaerobic bacteria may reflect microbiota disruption and disease progression in the CF lung. PMID:25992575

  19. Improvement of bacterial clearance and relief of clinical signs of Salmonella enterica serovar Typhimurium infection in pigs through upregulation of Th 1-specific responses by administration of a combination of two silicate minerals, biotite and bentonite

    PubMed Central

    LEE, Jin-A; JUNG, Bock-Gie; KIM, Tae-Hoon; KIM, Yun-Mi; KOH, Hong-Bum; LEE, Bong-Joo

    2015-01-01

    Biotite and bentonite are phyllosilicate minerals that were originally used in industrial applications. Several beneficial activities of them have recently been reported, especially regulation of the immune system and antimicrobial effects. Therefore, we investigated the immune-enhancing and bacterial clearance effects of a biotite and bentonite mixture (BBM) on experimental infection of Salmonella enterica serovar Typhimurium (S. Typhimurium) to determine whether the BBM could be used as an alternative antibiotic. We administered 1% or 2% BBM as a feed supplement. We then evaluated the bacterial clearance effects of the BBM against S. Typhimurium. We also evaluated the immune-enhancing effect of the BBM through several immunological experiments that included examination of the lysozyme activity, CD4+/CD8+ T lymphocyte ratio and the T-helper type 1 (Th 1) cytokine profile. The clinical signs of S. Typhimurium and the number of viable bacteria in feces and tissues were significantly decreased in both BBM groups, especially in the 2% BBM group. The BBM also markedly enhanced the lysozyme activity, CD4+/CD8+ T lymphocyte ratio and expression levels of IFN-γ and IL-12 in S. Typhimurium-challenged pigs. Therefore, the BBM could be a good candidate as an alternative antibiotic that improves Th 1-specific immune responses and the bacterial clearance effect. PMID:25947887

  20. A vaccine based on a mutant transferrin binding protein B of Haemophilus parasuis induces a strong T-helper 2 response and bacterial clearance after experimental infection.

    PubMed

    Martínez-Martínez, Sonia; Frandoloso, Rafael; Rodríguez-Ferri, Elías-Fernando; García-Iglesias, María-José; Pérez-Martínez, Claudia; Álvarez-Estrada, Álvaro; Gutiérrez-Martín, César-Bernardo

    2016-10-15

    This study aimed to characterize the type of immune response induced by an experimental vaccine based on a mutant Haemophilus parasuis transferrin binding protein (Tbp) B (Y167A) defective in its ability to bind porcine transferrin. Clinical and pathological signs, bacterial clearance, antibody response and the cytokine profile in alveolar macrophages and spleen after the vaccination and challenge of twenty-two colostrum-deprived pigs with 10(8) CFU of H. parasuis were analysed. Pigs vaccinated with Y167A were compared to those vaccinated with native TbpB (nTbpB), those treated with a commercial bacterin (CB) against Glässer's disease, those unvaccinated challenged (CH) and those unvaccinated unchallenged (UNCH) pigs. The rectal temperatures of Y167A pigs resembled those of UNCH pigs and were significantly lower than those of the nTbpB, CB and CH animals. A major reduction in pathological changes of the challenged pigs was observed in the Y167A group. H. parasuis was cleared from 88.9% of the samples from Y167A pigs versus 60.0% and 55.6% from those of the CB and nTbpB groups, respectively. The antibody response elicited by Y167A by ELISA was notably higher than that observed for nTbpB and CB pigs and was capable of preventing the expression and secretion of IL-8. The expression of IL-4 and IL-5, which were associated with the specific antibody levels, suggests that the main mechanism of protection conferred by Y167A vaccine is based on a strong T-helper 2 response. PMID:27590421

  1. MyD88 Deficiency Markedly Worsens Tissue Inflammation and Bacterial Clearance in Mice Infected with Treponema pallidum, the Agent of Syphilis

    PubMed Central

    Silver, Adam C.; Dunne, Dana W.; Zeiss, Caroline J.; Bockenstedt, Linda K.; Radolf, Justin D.; Salazar, Juan C.; Fikrig, Erol

    2013-01-01

    Research on syphilis, a sexually transmitted infection caused by the non-cultivatable spirochete Treponema pallidum, has been hampered by the lack of an inbred animal model. We hypothesized that Toll-like receptor (TLR)-dependent responses are essential for clearance of T. pallidum and, consequently, compared infection in wild-type (WT) mice and animals lacking MyD88, the adaptor molecule required for signaling by most TLRs. MyD88-deficient mice had significantly higher pathogen burdens and more extensive inflammation than control animals. Whereas tissue infiltrates in WT mice consisted of mixed mononuclear and plasma cells, infiltrates in MyD88-deficient animals were predominantly neutrophilic. Although both WT and MyD88-deficient mice produced antibodies that promoted uptake of treponemes by WT macrophages, MyD88-deficient macrophages were deficient in opsonophagocytosis of treponemes. Our results demonstrate that TLR-mediated responses are major contributors to the resistance of mice to syphilitic disease and that MyD88 signaling and FcR-mediated opsonophagocytosis are linked to the macrophage-mediated clearance of treponemes. PMID:23940747

  2. Sociable Sequences and Diminishing Functions.

    ERIC Educational Resources Information Center

    Sprows, David

    1989-01-01

    A FORTRAN program is provided for use with computer projects for a course in number theory. Uses diminishing functions and the speed of the computer to quickly determine possible solutions to problems. (MVL)

  3. Pre-adapting parasitic phages to a pathogen leads to increased pathogen clearance and lowered resistance evolution with Pseudomonas aeruginosa cystic fibrosis bacterial isolates.

    PubMed

    Friman, V-P; Soanes-Brown, D; Sierocinski, P; Molin, S; Johansen, H K; Merabishvili, M; Pirnay, J-P; De Vos, D; Buckling, A

    2016-01-01

    Recent years have seen renewed interest in phage therapy--the use of viruses to specifically kill disease-causing bacteria--because of the alarming rise in antibiotic resistance. However, a major limitation of phage therapy is the ease at with bacteria can evolve resistance to phages. Here, we determined whether in vitro experimental coevolution can increase the efficiency of phage therapy by limiting the resistance evolution of intermittent and chronic cystic fibrosis Pseudomonas aeruginosa lung isolates to four different phages. We first pre-adapted all phage strains against all bacterial strains and then compared the efficacy of pre-adapted and nonadapted phages against ancestral bacterial strains. We found that evolved phages were more efficient in reducing bacterial densities than ancestral phages. This was primarily because only 50% of bacterial strains were able to evolve resistance to evolved phages, whereas all bacteria were able to evolve some level of resistance to ancestral phages. Although the rate of resistance evolution did not differ between intermittent and chronic isolates, it incurred a relatively higher growth cost for chronic isolates when measured in the absence of phages. This is likely to explain why evolved phages were more effective in reducing the densities of chronic isolates. Our data show that pathogen genotypes respond differently to phage pre-adaptation, and as a result, phage therapies might need to be individually adjusted for different patients. PMID:26476097

  4. Inhibition of High-Mobility Group Box 1 Protein (HMGB1) Enhances Bacterial Clearance and Protects against Pseudomonas Aeruginosa Pneumonia in Cystic Fibrosis

    PubMed Central

    Entezari, Maria; Weiss, Daniel J; Sitapara, Ravikumar; Whittaker, Laurie; Wargo, Matthew J; Li, JianHua; Wang, Haichao; Yang, Huan; Sharma, Lokesh; Phan, Binh D; Javdan, Mohammad; Chavan, Sangeeta S; Miller, Edmund J; Tracey, Kevin J; Mantell, Lin L

    2012-01-01

    Pulmonary infection with Pseudomonas aeruginosa and neutrophilic lung inflammation significantly contribute to morbidity and mortality in cystic fibrosis (CF). High-mobility group box 1 protein (HMGB1), a ubiquitous DNA binding protein that promotes inflammatory tissue injury, is significantly elevated in CF sputum. However, its mechanistic and potential therapeutic implications in CF were previously unknown. We found that HMGB1 levels were significantly elevated in bronchoalveolar lavage fluids (BALs) of CF patients and cystic fibrosis transmembrane conductance regulator (CFTR )−/− mice. Neutralizing anti-HMGB1 monoclonal antibody (mAb) conferred significant protection against P. aeruginosa–induced neutrophil recruitment, lung injury and bacterial infection in both CFTR−/− and wild-type mice. Alveolar macrophages isolated from mice treated with anti-HMGB1 mAb had improved phagocytic activity, which was suppressed by direct exposure to HMGB1. In addition, BAL from CF patients significantly impaired macrophage phagocytotic function, and this impairment was attenuated by HMGB1-neutralizing antibodies. The HMGB1-mediated suppression of bacterial phagocytosis was attenuated in macrophages lacking toll-like receptor (TLR)-4, suggesting a critical role for TLR4 in signaling HMGB1-mediated macrophage dysfunction. These studies demonstrate that the elevated levels of HMGB1 in CF airways are critical for neutrophil recruitment and persistent presence of P. aeruginosa in the lung. Thus, HMGB1 may provide a therapeutic target for reducing bacterial infection and lung inflammation in CF. PMID:22314397

  5. Diminishing Returns in Humanities Research

    ERIC Educational Resources Information Center

    Bauerlein, Mark

    2009-01-01

    The author discusses the shift from criticism-as-explanation to criticism-as-performance that has taken place in literary criticism over the past five decades, and the resultant surge in published offerings to what has become a diminishing audience. The question of supersaturation applies to the institutions that demand and reward humanities…

  6. Mucus clearance, MyD88-dependent and MyD88-independent immunity modulate lung susceptibility to spontaneous bacterial infection and inflammation

    PubMed Central

    Livraghi-Butrico, Alessandra; Kelly, E. Jane; Klem, Erich R.; Dang, Hong; Wolfgang, Matthew C.; Boucher, Richard C.; Randell, Scott H.; O’Neal, Wanda K.

    2012-01-01

    It has been postulated that mucus stasis is central to the pathogenesis of obstructive lung diseases. In Scnn1b-transgenic (Scnn1b-Tg+) mice, airway-targeted overexpression of the epithelial Na+ channel β subunit causes airway surface dehydration, which results in mucus stasis and inflammation. Bronchoalveolar lavage from neonatal Scnn1b-Tg+ mice, but not wild-type littermates, contained increased mucus, bacteria, and neutrophils, which declined with age. Scnn1b-Tg+ mice lung bacterial flora included environmental and oropharyngeal species, suggesting inhalation and/or aspiration as routes of entry. Genetic deletion of the Toll/Interleukin-1 receptor adapter molecule MyD88 in Scnn1b-Tg+ mice did not modify airway mucus obstruction, but caused defective neutrophil recruitment and increased bacterial infection, which persisted into adulthood. Scnn1b-Tg+ mice derived into germ-free conditions exhibited mucus obstruction similar to conventional Scnn1b-Tg+ mice and sterile inflammation. Collectively, these data suggest that dehydration-induced mucus stasis promotes infection, compounds defects in other immune mechanisms, and alone is sufficient to trigger airway inflammation. PMID:22419116

  7. Arginine-supplemented diets improve survival in gut-derived sepsis and peritonitis by modulating bacterial clearance. The role of nitric oxide.

    PubMed Central

    Gianotti, L; Alexander, J W; Pyles, T; Fukushima, R

    1993-01-01

    OBJECTIVE: The effect of arginine on survival rates and host defense mechanisms was studied using two clinically relevant models of infection that included transfusion-induced immunosuppression. SUMMARY BACKGROUND DATA: Dietary arginine will improve resistance to infection but its role in transfusion-induced immunosuppression and bacterial translocation (gut-derived sepsis) has not been defined. METHODS: Balb/c mice were fed for 10 days with either a defined AIN-76A diet, an AIN-76A diet supplemented with 2% arginine, an AIN-76A diet supplemented with 4% glycine, or standard laboratory chow. In most experiments, the mice were then transfused with allogeneic blood and allowed to feed for an additional 5 days before undergoing either cecal ligation and puncture (CLP) or gavage with 10(10) Escherichia coli and a 20% burn injury. Additional animals fed with the arginine supplemented diet were treated with the nitric oxide inhibitor N omega-Nitro-L-arginine (NNA) before gavage and burn. The effect of these diets and NNA on the degree of translocation of 14C-radiolabeled E. coli from the intestine and the ability of the host to kill translocated organisms was also investigated. Mice were fed and received transfusion, gavage, and burn as above. Mesenteric lymph nodes (MLN), liver and spleen were harvested 4 hours postburn. RESULTS: Survival after CLP was 56% in the arginine-supplemented group versus 28% in the AIN-76A group and 20% in the chow group (p < 0.02). After gavage and burn, survival was 100% in the arginine-supplemented group versus 50% in both the glycine-supplemented and chow groups and 35% in the AIN-76A group (p < 0.01). In animals receiving the arginine-supplemented diet, treatment with NNA decreased survival from 95% to 30.5% (p < 0.0001). Greater translocation, as measured by radionuclide counts, was observed to the MLN of the AIN-76A group. However, there was no difference in translocation to the liver and spleen related to dietary group. Quantitative

  8. Acute psychological stress reduces plasma triglyceride clearance.

    PubMed

    Stoney, Catherine M; West, Sheila G; Hughes, Joel W; Lentino, Lisa M; Finney, Montenique L; Falko, James; Bausserman, Linda

    2002-01-01

    Acute stress elevates blood lipids, with the largest increases among men and postmenopausal women. The mechanisms for the effect are unknown, but may be due to altered lipid metabolism. This study investigated if acute stress induces transient reductions in triglyceride clearance in middle-aged men and women, and determined if gender and menopause affect triglyceride metabolism. Of the 35 women, half were premenopausal, and half were naturally postmenopausal; men (n = 35) were age matched. Clearance of an intravenously administered fat emulsion was assessed twice: once during a nonstress session, and again during a stress-testing session. During the stress session, a battery of behavioral stressors (serial subtraction, speech, mirror tracing, and Stroop) were performed for 40 min. The clearance rate of exogenous fat was significantly diminished during the stress, relative to the nonstress session. Women had more efficient clearance, relative to men, but there were no effects of menopausal status. The diminished ability to clear an intravenous fat emulsion during stress suggests one mechanism for stress-induced elevations in lipids. PMID:12206298

  9. Gait Variability in Chronic Back Pain Sufferers With Experimentally Diminished Visual Feedback: A Pilot Study.

    PubMed

    Hamacher, Dennis; Hamacher, Daniel; Krowicki, Martin; Schega, Lutz

    2016-01-01

    Increased gait variability is common in chronic low back pain patients, which is a sign of their diminished proprioceptive feedback. When proprioceptive information is reduced, vision partly takes over the role of proprioception. Therefore, a loss of visual feedback would have a more negative effect in individuals with diminished proprioception. To test this hypothesis, 14 healthy individuals and 14 chronic low back pain patients walked with and without impairment goggles manipulating visual feedback. The variability of stride time, stride length, and minimum foot clearance was evaluated. The authors observed an interaction effect regarding minimum foot clearance variability indicating that pain patients showed higher gait variability with manipulated visual feedback. Reduced vision may cause exceeded tripping risk in individuals with diminished proprioception. PMID:26339981

  10. Diminishing Marginal Utility in Economics Textbooks

    ERIC Educational Resources Information Center

    Dittmer, Timothy

    2005-01-01

    Many introductory microeconomics textbook authors derive the law of demand from the assumption of diminishing marginal utility. Authors of intermediate and graduate textbooks derive demand from diminishing marginal rate of substitution and ordinal preferences. These approaches are not interchangeable; diminishing marginal utility for all goods is…

  11. Advanced Thermal HPT Clearance Control

    NASA Technical Reports Server (NTRS)

    WojciechVoytek, Sak

    2006-01-01

    OBJECTIVE: Develop a fast acting HPT Active Clearance Control System to improve engine efficiency and reduce emissions CHALLENGE: Reduction of HPT blade clearance throughout engine operation System complexity, reliability and cost must remain comparable or surpass today s engines Reduced clearance may increase possibility of rubs

  12. Does Public Employee Unionism Diminish Democracy?

    ERIC Educational Resources Information Center

    Cohen, Sanford

    1979-01-01

    The author considers charges that public sector unionism diminishes democracy by requiring a sharing of public authority with private bodies that too often exerts disproportionate influence on government decisions. He questions these charges in view of declining public unionism and unrealistic assumptions about the nature of local government…

  13. Renal Clearance of Nanoparticles

    PubMed Central

    Choi, Hak Soo; Liu, Wenhao; Misra, Preeti; Tanaka, Eiichi; Zimmer, John P.; Ipe, Binil Itty; Bawendi, Moungi G.; Frangioni, John V.

    2008-01-01

    SUMMARY The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using quantum dots (QDs) as a model system, we have precisely defined the requirements for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles. Zwitterionic or neutral organic coatings prevented adsorption of serum proteins, which otherwise increased hydrodynamic diameter (HD) by over 15 nm and prevented renal excretion. A final HD smaller than 5.5 nm resulted in rapid and efficient urinary excretion, and elimination of QDs from the body. This study provides a foundation for the design and development of biologically targeted nanoparticles for biomedical applications. PMID:17891134

  14. Diminished Schwann cell repair responses underlie age-associated impaired axonal regeneration

    PubMed Central

    Painter, Michio W.; Brosius Lutz, Amanda; Cheng, Yung-Chih; Latremoliere, Alban; Duong, Kelly; Miller, Christine M.; Posada, Sean; Cobos, Enrique J.; Zhang, Alice X.; Wagers, Amy J.; Havton, Leif A.; Barres, Ben; Omura, Takao

    2014-01-01

    SUMMARY The regenerative capacity of the peripheral nervous system declines with age. Why this occurs, however, is unknown. We demonstrate that 24-month old mice exhibit an impairment of functional recovery after nerve injury compared to 2-month old animals. We find no difference in the intrinsic growth capacity between aged and young sensory neurons in vitro nor in their ability to activate growth-associated transcriptional programs after injury. Instead, using age-mismatched nerve transplants in vivo, we show that the extent of functional recovery depends on the age of the nerve graft, and not the age of the host. Molecular interrogation of the sciatic nerve reveals that aged Schwann cells (SCs) fail to rapidly activate a transcriptional repair program after injury. Functionally, aged SCs exhibit impaired de-differentiation, myelin clearance and macrophage recruitment. These results suggest that the age-associated decline in axonal regeneration results from diminished Schwann cell plasticity, leading to slower myelin clearance. PMID:25033179

  15. Diminished Schwann cell repair responses underlie age-associated impaired axonal regeneration.

    PubMed

    Painter, Michio W; Brosius Lutz, Amanda; Cheng, Yung-Chih; Latremoliere, Alban; Duong, Kelly; Miller, Christine M; Posada, Sean; Cobos, Enrique J; Zhang, Alice X; Wagers, Amy J; Havton, Leif A; Barres, Ben; Omura, Takao; Woolf, Clifford J

    2014-07-16

    The regenerative capacity of the peripheral nervous system declines with age. Why this occurs, however, is unknown. We demonstrate that 24-month-old mice exhibit an impairment of functional recovery after nerve injury compared to 2-month-old animals. We find no difference in the intrinsic growth capacity between aged and young sensory neurons in vitro or in their ability to activate growth-associated transcriptional programs after injury. Instead, using age-mismatched nerve transplants in vivo, we show that the extent of functional recovery depends on the age of the nerve graft, and not the age of the host. Molecular interrogation of the sciatic nerve reveals that aged Schwann cells (SCs) fail to rapidly activate a transcriptional repair program after injury. Functionally, aged SCs exhibit impaired dedifferentiation, myelin clearance, and macrophage recruitment. These results suggest that the age-associated decline in axonal regeneration results from diminished Schwann cell plasticity, leading to slower myelin clearance. PMID:25033179

  16. Site clearance working group

    SciTech Connect

    1997-03-01

    The Gulf of Mexico and Louisiana continue to be areas with a high level of facility removal, and the pace of removal is projected to increase. Regulations were promulgated for the Gulf of Mexico and Louisiana requiring that abandoned sites be cleared of debris that could interfere with fishing and shrimping activities. The site clearance regulations also required verification that the sites were clear. Additionally, government programs were established to compensate fishermen for losses associated with snagging their equipment on oil and gas related objects that remained on the water bottoms in areas other than active producing sites and sites that had been verified as clear of obstructions and snags. The oil and gas industry funds the compensation programs. This paper reviews the regulations and evolving operating practices in the Gulf of Mexico and Louisiana where site clearance and fisherman`s gear compensation regulations have been in place for a number of years. Although regulations and guidelines may be in place elsewhere in the world, this paper focuses on the Gulf of Mexico and Louisiana. Workshop participants are encouraged to bring up international issues during the course of the workshop. Additionally, this paper raises questions and focuses on issues that are of concern to the various Gulf of Mexico and Louisiana water surface and water bottom stakeholders. This paper does not have answers to the questions or issues. During the workshop participants will debate the questions and issues in an attempt to develop consensus opinions and/or make suggestions that can be provided to the appropriate organizations, both private and government, for possible future research or policy adjustments. Site clearance and facility removal are different activities. Facility removal deals with removal of the structures used to produce oil and gas including platforms, wells, casing, piles, pipelines, well protection structures, etc.

  17. Turbomachinery Clearance Control

    NASA Technical Reports Server (NTRS)

    Chupp, Raymond E.; Hendricks, Robert C.; Lattime, Scott B.; Steinetz, Bruce M.; Aksit, Mahmut F.

    2007-01-01

    Controlling interface clearances is the most cost effective method of enhancing turbomachinery performance. Seals control turbomachinery leakages, coolant flows and contribute to overall system rotordynamic stability. In many instances, sealing interfaces and coatings are sacrificial, like lubricants, giving up their integrity for the benefit of the component. They are subjected to abrasion, erosion, oxidation, incursive rubs, foreign object damage (FOD) and deposits as well as extremes in thermal, mechanical, aerodynamic and impact loadings. Tribological pairing of materials control how well and how long these interfaces will be effective in controlling flow. A variety of seal types and materials are required to satisfy turbomachinery sealing demands. These seals must be properly designed to maintain the interface clearances. In some cases, this will mean machining adjacent surfaces, yet in many other applications, coatings are employed for optimum performance. Many seals are coating composites fabricated on superstructures or substrates that are coated with sacrificial materials which can be refurbished either in situ or by removal, stripping, recoating and replacing until substrate life is exceeded. For blade and knife tip sealing an important class of materials known as abradables permit blade or knife rubbing without significant damage or wear to the rotating element while maintaining an effective sealing interface. Most such tip interfaces are passive, yet some, as for the high-pressure turbine (HPT) case or shroud, are actively controlled. This work presents an overview of turbomachinery sealing. Areas covered include: characteristics of gas and steam turbine sealing applications and environments, benefits of sealing, types of standard static and dynamics seals, advanced seal designs, as well as life and limitations issues.

  18. Indole and 7-hydroxyindole diminish Pseudomonas aeruginosa virulence.

    PubMed

    Lee, Jintae; Attila, Can; Cirillo, Suat L G; Cirillo, Jeffrey D; Wood, Thomas K

    2009-01-01

    Indole is an extracellular biofilm signal for Escherichia coli, and many bacterial oxygenases readily convert indole to various oxidized compounds including 7-hydroxyindole (7HI). Here we investigate the impact of indole and 7HI on Pseudomonas aeruginosa PAO1 virulence and quorum sensing (QS)-regulated phenotypes; this strain does not synthesize these compounds but degrades them rapidly. Indole and 7HI both altered extensively gene expression in a manner opposite that of acylhomoserine lactones; the most repressed genes encode the mexGHI-opmD multidrug efflux pump and genes involved in the synthesis of QS-regulated virulence factors including pyocyanin (phz operon), 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS) signal (pqs operon), pyochelin (pch operon) and pyoverdine (pvd operon). Corroborating these microarray results, indole and 7HI decreased production of pyocyanin, rhamnolipid, PQS and pyoverdine and enhanced antibiotic resistance. In addition, indole affected the utilization of carbon, nitrogen and phosphorus, and 7HI abolished swarming motility. Furthermore, 7HI reduced pulmonary colonization of P. aeruginosa in guinea pigs and increased clearance in lungs. Hence, indole-related compounds have potential as a novel antivirulence approach for the recalcitrant pathogen P. aeruginosa. PMID:21261883

  19. Monocyte Trafficking to Hepatic Sites of Bacterial Infection Is Chemokine Independent and Directed by Focal Intercellular Adhesion Molecule-1 Expression

    PubMed Central

    Shi, Chao; Velázquez, Peter; Hohl, Tobias M.; Leiner, Ingrid; Dustin, Michael L.; Pamer, Eric G.

    2010-01-01

    Recruitment of CCR2+Ly6Chigh monocytes to sites of infection is essential for efficient clearance of microbial pathogens. Although CCR2-mediated signals promote monocyte emigration from bone marrow, the contribution of CCR2 to later stages of monocyte recruitment remains unresolved. In this article, we show that CCR2 deficiency markedly worsens hepatic Listeria monocytogenes infection because Ly6Chigh monocytes are retained in the bone marrow. Intravenously transferred, CCR2-deficient Ly6Chigh monocytes traffic normally to hepatic foci of infection and contribute to bacterial clearance. Pertussis toxin treatment of adoptively transferred monocytes does not impair their intrahepatic trafficking, suggesting that chemokine signaling, once CCR2+ Ly6Chigh monocytes emigrate from the bone marrow, is not required for monocyte localization to sites of bacterial infection in the liver. Expression of ICAM-1 is induced in close proximity to foci of bacterial infection in the liver, including on CD31+ endothelial cells, and blockade of CD11b and CD44 diminishes monocyte localization to these hepatic foci. Our studies demonstrated that Ly6Chigh monocyte recruitment from the bloodstream to the L. monocytogenes-infected liver does not require chemokine receptor-mediated signals but instead is principally dependent on integrin- and extracellular matrix-mediated monocyte adhesion. PMID:20435926

  20. Diminishing returns in bovine tuberculosis control.

    PubMed

    Hone, J

    2013-07-01

    Mycobacterium bovis causes bovine tuberculosis (bTB) in many mammals including cattle, deer and brushtail possum. The aim of this study was to estimate the strength of association, using model selection (AICc) regression analyses, between the proportion of cattle and farmed deer herds with bTB in New Zealand and annual costs of TB control, namely disease control in livestock, in wildlife or in a combination of the two. There was more support for curved (concave up) than linear models which related the proportion of cattle and farmed deer herds with bTB to the annual control costs. The curved, concave-up, best-fitting relationships showed diminishing returns with no positive asymptote and implied TB eradication is feasible in New Zealand. PMID:23632097

  1. Airway clearance in neuromuscular weakness.

    PubMed

    Gauld, Leanne Maree

    2009-05-01

    Impaired airway clearance leads to recurrent chest infections and respiratory deterioration in neuromuscular weakness. It is frequently the cause of death. Cough is the major mechanism of airway clearance. Cough has several components, and assessment tools are available to measure the different components of cough. These include measuring peak cough flow, respiratory muscle strength, and inspiratory capacity. Each is useful in assessing the ability to generate an effective cough, and can be used to guide when techniques of assisting airway clearance may be effective for the individual and which are most effective. Techniques to assist airway clearance include augmenting inspiration by air stacking, augmenting expiration by assisting the cough, and augmenting both inspiration and expiration with the mechanical insufflator-exsufflator or by direct suctioning via a tracheostomy. Physiotherapists are invaluable in assisting airway clearance, and in teaching patients and their families how to use these techniques. Use of the mechanical insufflator-exsufflator has gained popularity in recent times, but several simpler, more economical methods are available to assist airway clearance that can be used effectively alone or in combination. This review examines the literature available on the assessment and management of impaired airway clearance in neuromuscular weakness. PMID:19379290

  2. Method of mucociliary clearance assessment

    NASA Astrophysics Data System (ADS)

    Danilova, Tatiana V.; Manturov, Alexey O.; Ermakov, Igor Y.; Mareev, Gleb O.; Mareev, Oleg V.

    2016-04-01

    The article is devoted to the research capabilities of mucociliary clearance in the nasal cavity and paranasal sinuses using modern techniques of digital video recording and processing. We describe the setup and software for this method and the results of our research. Using microscope and digital camera we can provide a good method to study mucociliary clearance and by usage of special software we able to measure some characteristic of nasal mucosae and its main function.

  3. Dual clearance squeeze film damper

    NASA Technical Reports Server (NTRS)

    Fleming, D. P. (Inventor)

    1985-01-01

    A dual clearance hydrodynamic liquid squeeze film damper for a gas turbine engine is described. Under normal operating conditions, the device functions as a conventional squeeze film damper, using only one of its oil films. When an unbalance reaches abusive levels, as may occur with a blade loss or foreign object damage, a second, larger clearance film becomes active, controlling vibration amplitudes in a near optimum manner until the engine can be safely shut down and repaired.

  4. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... takeoffs and landings. (c) Water clearance. There must be a clearance of at least 18 inches between each propeller and the water, unless compliance with § 23.239 can be shown with a lesser clearance. (d... airplane structure, plus any additional radial clearance necessary to prevent harmful vibration; (2)...

  5. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... takeoffs and landings. (c) Water clearance. There must be a clearance of at least 18 inches between each propeller and the water, unless compliance with § 23.239 can be shown with a lesser clearance. (d... airplane structure, plus any additional radial clearance necessary to prevent harmful vibration; (2)...

  6. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... takeoffs and landings. (c) Water clearance. There must be a clearance of at least 18 inches between each propeller and the water, unless compliance with § 23.239 can be shown with a lesser clearance. (d... airplane structure, plus any additional radial clearance necessary to prevent harmful vibration; (2)...

  7. Seasonal control of particle clearance by isolated gills from the clam Mercenaria mercenaria.

    PubMed

    Gainey, Louis F

    2007-07-01

    Pieces of gill isolated from the clam Mercenaria mercenaria clear colloidal graphite from seawater, and the clearance rates are measurable. 5-Hydroxytryptamine (5-HT) had a biphasic effect on clearance rates: concentrations from 10(-6) to 10(-5) mol l(-1) 5-HT increased clearance, but higher concentrations reduced it. During the summer, the gills were less responsive to 5-HT: the threshold increased from 1 x 10(-6) to 5 x 10(-6) mol l(-1), and although the rate was still maximal at 10(-5) mol l(-1), it was significantly lower than the maximal rate in the winter. At 10(-5) mol l(-1) 5-HT, which maximized clearance, the lateral cilia were active, the interfilament space decreased and the diameter of the water tubes increased. Higher concentrations of 5-HT contracted the gill musculature, which inhibited the lateral cilia, decreased the interfilament space even more and decreased the diameter of the water tubes. The nitric oxide (NO) generator DEANO stimulated clearance in the winter but had no effect during the summer. L-NAME, an inhibitor of NO synthesis, diminished the effect of 5-HT during the winter but was ineffective during the summer. The diminished response to 5-HT of winter gills treated with L-NAME was statistically equal to the response of the gills to 5-HT during the summer. Dopamine (DA) inhibited clearance, and the gills were more sensitive to DA in winter than in summer. Microscopic examination of untreated gills revealed little or no lateral ciliary activity, and clearance was minimal. Thus, clearance rates of isolated gills behave in a manner consistent with the seasonality and pharmacology of the lateral cilia and branchial musculature. PMID:17601956

  8. Central role for PICALM in amyloid-β blood-brain barrier transcytosis and clearance.

    PubMed

    Zhao, Zhen; Sagare, Abhay P; Ma, Qingyi; Halliday, Matthew R; Kong, Pan; Kisler, Kassandra; Winkler, Ethan A; Ramanathan, Anita; Kanekiyo, Takahisa; Bu, Guojun; Owens, Nelly Chuqui; Rege, Sanket V; Si, Gabriel; Ahuja, Ashim; Zhu, Donghui; Miller, Carol A; Schneider, Julie A; Maeda, Manami; Maeda, Takahiro; Sugawara, Tohru; Ichida, Justin K; Zlokovic, Berislav V

    2015-07-01

    PICALM is a highly validated genetic risk factor for Alzheimer's disease (AD). We found that reduced expression of PICALM in AD and murine brain endothelium correlated with amyloid-β (Aβ) pathology and cognitive impairment. Moreover, Picalm deficiency diminishedclearance across the murine blood-brain barrier (BBB) and accelerated Aβ pathology in a manner that was reversible by endothelial PICALM re-expression. Using human brain endothelial monolayers, we found that PICALM regulated PICALM/clathrin-dependent internalization of Aβ bound to the low density lipoprotein receptor related protein-1, a key Aβ clearance receptor, and guided Aβ trafficking to Rab5 and Rab11, leading to Aβ endothelial transcytosis and clearance. PICALM levels and Aβ clearance were reduced in AD-derived endothelial monolayers, which was reversible by adenoviral-mediated PICALM transfer. Inducible pluripotent stem cell-derived human endothelial cells carrying the rs3851179 protective allele exhibited higher PICALM levels and enhanced Aβ clearance. Thus, PICALM regulates Aβ BBB transcytosis and clearance, which has implications for Aβ brain homeostasis and clearance therapy. PMID:26005850

  9. Central role for PICALM in amyloid–β blood–brain barrier transcytosis and clearance

    PubMed Central

    Zhao, Zhen; Sagare, Abhay P.; Ma, Qingyi; Halliday, Matthew R.; Kong, Pan; Kisler, Kassandra; Winkler, Ethan A.; Ramanathan, Anita; Kanekiyo, Takahisa; Bu, Guojun; Owens, Nelly Chuqui; Rege, Sanket V.; Si, Gabriel; Ahuja, Ashim; Zhu, Donghui; Miller, Carol A.; Schneider, Julie A.; Maeda, Manami; Maeda, Takahiro; Sugawara, Tohru; Ichida, Justin K.; Zlokovic, Berislav V.

    2015-01-01

    PICALM is highly validated genetic risk factor for Alzheimer’s disease (AD). Here, we report that PICALM reductions in AD and murine brain endothelium correlate with amyloid–β (Aβ) pathology and cognitive impairment. Moreover, Picalm deficiency diminishesclearance across the murine blood–brain barrier (BBB) and accelerates Aβ pathology that is reversible by endothelial PICALM re–expression. Using human brain endothelial monolayer, we show that PICALM regulates PICALM/clathrin–dependent internalization of Aβ bound to the low density lipoprotein receptor related protein–1, a key Aβ clearance receptor, and guides Aβ trafficking to Rab5 and Rab11 leading to Aβ endothelial transcytosis and clearance. PICALM levels and Aβ clearance were reduced in AD–derived endothelial monolayers, which was reversible by adenoviral–mediated PICALM transfer. iPSC–derived human endothelial cells carrying the rs3851179 protective allele exhibited higher PICALM levels and enhanced Aβ clearance. Thus, PICALM regulates Aβ BBB transcytosis and clearance that has implications for Aβ brain homeostasis and clearance therapy. PMID:26005850

  10. Refrigeration system with clearance seals

    SciTech Connect

    Holland, N. J.

    1985-02-26

    In a refrigeration system such as a split Stirling system, fluid seals associated with the reciprocating displacer are virtually dragless clearance seals. Movement of the displacer relative to the pressure variations in the working volume of gas is retarded by a discrete braking element. Because it is not necessary that the brake providing any sealing action, the brake can be designed for greater durability and less dependence on ambient and operating temperatures. Similarly, the clearance seal can be formed of elements having low thermal expansion such that the seal is not temperature dependent. In the primary embodiments the braking element is a split friction brake.

  11. Inherited Disorders of Bilirubin Clearance

    PubMed Central

    Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

    2016-01-01

    Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

  12. Noninvasive clearance of airway secretions.

    PubMed

    Hardy, K A; Anderson, B D

    1996-06-01

    Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases

  13. Dual-Track Clearance of Circulating Bacteria Balances Rapid Restoration of Blood Sterility with Induction of Adaptive Immunity.

    PubMed

    Broadley, Steven P; Plaumann, Ann; Coletti, Raffaele; Lehmann, Christin; Wanisch, Andreas; Seidlmeier, Amelie; Esser, Knud; Luo, Shanshan; Rämer, Patrick C; Massberg, Steffen; Busch, Dirk H; van Lookeren Campagne, Menno; Verschoor, Admar

    2016-07-13

    Efficient clearance of bacteremia prevents life-threatening disease. Platelet binding to intravascular bacteria, a process involving platelet glycoprotein GPIb and bacterial opsonization with activated complement C3, influences blood clearance and anti-infective immunity. Using intravital microscopy of the bloodstream of mice infected with Listeria monocytogenes, we show that bacterial clearance is not a uniform process but a "dual-track" mechanism consisting of parallel "fast" and "slow" pathways. "Slow clearance" is regulated by time-dependent bacterial opsonization, stochastic platelet binding, and capture of bacteria-platelet-complexes via the complement receptor of the immunoglobulin superfamily, CRIg. The mechanism spares some bacteria from "fast clearance" and rapid destruction in the liver via Kupffer cell scavenger receptors, keeping them available for adaptive immunity induction by splenic CD8α(+) dendritic cells. We consistently find "fast" and "slow" clearance patterns for a broad panel of other Gram+ and Gram- bacteria. Thus, dual-track clearance balances rapid restoration of blood sterility with induction of specific antibacterial immunity. PMID:27345696

  14. Microwave Blade Tip Clearance System: An Update

    NASA Technical Reports Server (NTRS)

    Geisheimer, Jon

    2006-01-01

    Newer engines use compressor bleed air and a model to close clearances open loop. Measuring clearances and closing the control loop can add additional efficiencies. Tip clearance control has been identified as a key technology for future engines Additional benefits in prognostics, NSMS, and condition-based maintenance. In the HPT for every 1 mil improvement in clearance: a) SFC decreases 0.1%; and b) EGT margin increases 1 C.

  15. The Dynamics of Apoptotic Cell Clearance.

    PubMed

    Elliott, Michael R; Ravichandran, Kodi S

    2016-07-25

    The phagocytic clearance of dying cells in a tissue is a highly orchestrated series of intercellular events coordinated by a complex signaling network. Recent data from genetic, biochemical, and live-imaging approaches have greatly enhanced our understanding of the dynamics of cell clearance and how the process is orchestrated at the cellular and tissue levels. We discuss how networks regulating apoptotic cell clearance are integrated to enable a rapid, efficient, and high-capacity clearance system within tissues. PMID:27459067

  16. 29 CFR 1917.113 - Clearance heights.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Clearance heights. 1917.113 Section 1917.113 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.113 Clearance heights. Clearance heights shall...

  17. 30 CFR 56.11010 - Stairstep clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Stairstep clearance. 56.11010 Section 56.11010 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Travelways § 56.11010 Stairstep clearance. Vertical clearance...

  18. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... the corresponding landing gear strut bottomed. (b) Water clearance. There must be a clearance of at least 18 inches between each propeller and the water, unless compliance with § 25.239(a) can be shown... to prevent harmful vibration; (2) At least one-half inch longitudinal clearance between the...

  19. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... the corresponding landing gear strut bottomed. (b) Water clearance. There must be a clearance of at least 18 inches between each propeller and the water, unless compliance with § 25.239(a) can be shown... to prevent harmful vibration; (2) At least one-half inch longitudinal clearance between the...

  20. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... the corresponding landing gear strut bottomed. (b) Water clearance. There must be a clearance of at least 18 inches between each propeller and the water, unless compliance with § 25.239(a) can be shown... to prevent harmful vibration; (2) At least one-half inch longitudinal clearance between the...

  1. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a...

  2. 49 CFR 192.325 - Underground clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Underground clearance. 192.325 Section 192.325... Lines and Mains § 192.325 Underground clearance. (a) Each transmission line must be installed with at least 12 inches (305 millimeters) of clearance from any other underground structure not associated...

  3. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  4. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  5. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  6. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  7. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  8. 29 CFR 1917.113 - Clearance heights.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 7 2013-07-01 2013-07-01 false Clearance heights. 1917.113 Section 1917.113 Labor... (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.113 Clearance heights. Clearance heights shall be prominently posted where the height is insufficient for vehicles and equipment....

  9. 29 CFR 1917.113 - Clearance heights.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 7 2012-07-01 2012-07-01 false Clearance heights. 1917.113 Section 1917.113 Labor... (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.113 Clearance heights. Clearance heights shall be prominently posted where the height is insufficient for vehicles and equipment....

  10. 29 CFR 1917.113 - Clearance heights.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 7 2014-07-01 2014-07-01 false Clearance heights. 1917.113 Section 1917.113 Labor... (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.113 Clearance heights. Clearance heights shall be prominently posted where the height is insufficient for vehicles and equipment....

  11. 33 CFR 117.47 - Clearance gauges.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Clearance gauges. 117.47 Section 117.47 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS General Requirements § 117.47 Clearance gauges. (a) Clearance gauges are required for drawbridges across navigable waters...

  12. 33 CFR 117.47 - Clearance gauges.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Clearance gauges. 117.47 Section 117.47 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS General Requirements § 117.47 Clearance gauges. (a) Clearance gauges are required for drawbridges across navigable waters...

  13. 33 CFR 117.47 - Clearance gauges.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Clearance gauges. 117.47 Section 117.47 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS General Requirements § 117.47 Clearance gauges. (a) Clearance gauges are required for drawbridges across navigable waters...

  14. 33 CFR 117.47 - Clearance gauges.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Clearance gauges. 117.47 Section 117.47 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS General Requirements § 117.47 Clearance gauges. (a) Clearance gauges are required for drawbridges across navigable waters...

  15. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a...

  16. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a...

  17. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a...

  18. 29 CFR 1917.113 - Clearance heights.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 7 2011-07-01 2011-07-01 false Clearance heights. 1917.113 Section 1917.113 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.113 Clearance heights. Clearance heights shall...

  19. Removal - An alternative to clearance

    SciTech Connect

    Feinhals, J.; Kelch, A.; Kunze, V.

    2007-07-01

    This presentation shows the differences between the application of clearance and removal, both being procedures for materials leaving radiation protection areas permanently. The differentiation will be done on the basis of the German legislation but may be also applicable for other national legislation. For clearance in Germany two basic requirements must be given, i.e. that the materials are activated or contaminated and that they result from the licensed use or can be assigned to the scope of the license. Clearance needs not to be applied to objects in Germany which are to be removed only temporarily from controlled areas with the purpose of repair or reuse in other controlled areas. In these cases only the requirements of contamination control apply. In the case of removal it must either be proved by measurements that the relevant materials are neither activated nor contaminated or that the materials result from areas where activation or contamination is impossible due to the operational history considering operational procedures and events. If the material is considered neither activated nor contaminated there is no need for a clearance procedure. Therefore, these materials can be removed from radiation protection areas and the removal is in the responsibility of the licensee. Nevertheless, the removal procedure and the measuring techniques to be applied for the different types of materials need an agreement from the competent authority. In Germany a maximum value of 10% of the clearance values has been established in different licenses as a criterion for the application of removal. As approximately 2/3 of the total mass of a nuclear power plant is not expected to be contaminated or activated there is a need for such a procedure of removal for this non contaminated material without any regulatory control especially in the case of decommissioning. A remarkable example is NPP Stade where in the last three years more than 8600 Mg were disposed of by removal and

  20. The airborne survival of Pasteurella haemolytica and its deposition in and clearance from the mouse lung.

    PubMed

    Gilmour, M I; Wathes, C M; Taylor, F G

    1990-02-01

    Pasteurella haemolytica A1 was aerosolised by a Collison nebuliser in a Henderson apparatus and its survival in air was measured. The organism was fragile in aerosol and survived best at high humidity and warm temperature. Mice were exposed to the aerosol and clearance from the lung measured. Deposition in the mouse lung showed a good linear correlation with bacterial concentration in the spray suspension fluid. Clearance from the lung was rapid over 24 h although some bacteria could be detected 2 and 4 days after exposure. Mice which received a second exposure 2 weeks later exhibited accelerated clearance from the lung whereby no bacteria could be detected after 12 h. This was associated with serum IgG antibody production, and local and splenic lymphocyte responses to bacterial antigen in vitro. PMID:2138372

  1. Effects of dipyridamole-induced vasodilation on myocardial uptake and clearance kinetics of thallium-201

    SciTech Connect

    Beller, G.A.; Holzgrefe, H.H.; Watson, D.D.

    1983-12-01

    Myocardial thallium-201 (201Tl) uptake and clearance after intravenous administration of dipyridamole (150 micrograms/kg) were determined in 12 open-chest anesthetized dogs with a partial coronary artery stenosis. 201Tl (1.5 mCi) was injected intravenously and myocardial biopsy specimens were obtained 10 min, 60 min, and 2 hr after injection. Serial changes in 201Tl activity in the normal zone and in the zone of partial stenosis were correlated with microsphere-determined regional blood flow and distal coronary pressure. Another nine dogs with equivalent stenosis not given dipyridamole before 201Tl served as controls. Data indicate that dipyridamole-induced vasodilation in the presence of a partial stenosis results in diminished uptake and delayed clearance compared with increased uptake and more rapid clearance in normally perfused myocardium producing an initial 201Tl defect with delayed redistribution.

  2. MicroRNA-155 Is Required for Clearance of Streptococcus pneumoniae from the Nasopharynx

    PubMed Central

    Verschoor, Chris P.; Dorrington, Michael G.; Novakowski, Kyle E.; Kaiser, Julie; Radford, Katherine; Nair, Parameswaran; Anipindi, Varun; Kaushic, Charu; Surette, Michael G.

    2014-01-01

    Pneumonia caused by Streptococcus pneumoniae is a major cause of death and an economic burden worldwide. S. pneumoniae is an intermittent colonizer of the human upper respiratory tract, and the ability to control asymptomatic colonization determines the likelihood of developing invasive disease. Recognition of S. pneumoniae by resident macrophages via Toll-like receptor 2 (TLR-2) and the macrophage receptor with collagenous structure (MARCO) and the presence of interleukin-17 (IL-17)-secreting CD4+ T cells are required for macrophage recruitment and bacterial clearance. Despite the fact that the primary cellular effectors needed for bacterial clearance have been identified, much of the underlying regulatory mechanisms are unknown. Herein, we demonstrate that the small, noncoding RNA microRNA-155 (mir-155) is critical for the effective clearance of S. pneumoniae. Our studies show that mir-155-deficient mice maintain the ability to prevent acute invasive pneumococcal infection but have significantly higher bacterial burdens following colonization, independently of macrophage recognition by TLR-2, MARCO expression, or bactericidal capacity. The observed defects in bacterial clearance parallel reduced IL-17A and gamma interferon CD4+ T-cell responses in vivo, lower IL-17A mRNA levels in the nasopharynx, and a reduced capacity to induce Th17 cell polarization. Given that knockout mice are also limited in the capacity to generate high-titer S. pneumoniae-specific antibodies, we conclude that mir-155 is a critical mediator of the cellular effectors needed to clear primary and secondary S. pneumoniae colonizations. PMID:25156727

  3. Interventions for control of Salmonella: Clearance of Microbial growth from rubber picker fingers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study was conducted to determine if a surface material with antimicrobial properties combined with an effective disinfectant could achieve total clearance of bacterial contamination. Prior to beginning the project, new rubber picker fingers collected from three processing facilities were tested fo...

  4. Prediction of drug clearance in children.

    PubMed

    Foissac, Frantz; Bouazza, Naïm; Valade, Elodie; De Sousa Mendes, Mailys; Fauchet, Floris; Benaboud, Sihem; Hirt, Déborah; Tréluyer, Jean-Marc; Urien, Saïk

    2015-07-01

    The pediatric population is often exposed to drugs without sufficient knowledge about pharmacokinetics. The prediction of accurate clearance values in children, especially in neonates and infants, will improve the rational in dosing decisions. Drug clearances from birth to adulthood were compiled after a systematic review of pharmacokinetic reports. The analysis was performed using NONMEM. Clearance predictions were then evaluated by external validation. Prediction errors were also compared with those obtained from weight-based allometric scaling and physiologically based clearance (PBCL) models. For the analysis, 17 and 15 drugs were used for model building and external validation, respectively. A model based on the adult drug clearance value and taking into account both weight and age was retained. Age-related maturation of clearance reached 90% of the adult value within 1.5 years of life. For children less than 2 years old, allometric scaling alone systematically overestimated clearances. Accounting for age improved the clearance prediction in the 6 months-2 years age group (prediction error < 25%). Predictions obtained from the PBCL approach were close to our results. This analysis established a single equation using the adult clearance value as well as individual age and weight to predict drug clearance in children older than 6 months. PMID:25721251

  5. Necroptosis Promotes Staphylococcus aureus Clearance by Inhibiting Excessive Inflammatory Signaling.

    PubMed

    Kitur, Kipyegon; Wachtel, Sarah; Brown, Armand; Wickersham, Matthew; Paulino, Franklin; Peñaloza, Hernán F; Soong, Grace; Bueno, Susan; Parker, Dane; Prince, Alice

    2016-08-23

    Staphylococcus aureus triggers inflammation through inflammasome activation and recruitment of neutrophils, responses that are critical for pathogen clearance but are associated with substantial tissue damage. We postulated that necroptosis, cell death mediated by the RIPK1/RIPK3/MLKL pathway, would function to limit pathological inflammation. In models of skin infection or sepsis, Mlkl-/- mice had high bacterial loads, an inability to limit interleukin-1b (IL-1b) production, and excessive inflammation. Similarly, mice treated with RIPK1 or RIPK3 inhibitors had increased bacterial loads in a model of sepsis. Ripk3-/- mice exhibited increased staphylococcal clearance and decreased inflammation in skin and systemic infection, due to direct effects of RIPK3 on IL-1b activation and apoptosis. In contrast to Casp1/4-/- mice with defective S. aureus killing, the poor outcomes of Mlkl-/- mice could not be attributed to impaired phagocytic function. We conclude that necroptotic cell death limits the pathological inflammation induced by S. aureus. PMID:27524612

  6. Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins.

    PubMed

    Tyrkalska, Sylwia D; Candel, Sergio; Angosto, Diego; Gómez-Abellán, Victoria; Martín-Sánchez, Fátima; García-Moreno, Diana; Zapata-Pérez, Rubén; Sánchez-Ferrer, Álvaro; Sepulcre, María P; Pelegrín, Pablo; Mulero, Victoriano

    2016-01-01

    Inflammasomes are cytosolic molecular platforms that alert the immune system about the presence of infection. Here we report that zebrafish guanylate-binding protein 4 (Gbp4), an IFNγ-inducible GTPase protein harbouring a C-terminal CARD domain, is required for the inflammasome-dependent clearance of Salmonella Typhimurium (ST) by neutrophils in vivo. Despite the presence of the CARD domain, Gbp4 requires the universal inflammasome adaptor Asc for mediating its antibacterial function. In addition, the GTPase activity of Gbp4 is indispensable for inflammasome activation and ST clearance. Mechanistically, neutrophils are recruited to the infection site through the inflammasome-independent production of the chemokine (CXC motif) ligand 8 and leukotriene B4, and then mediate bacterial clearance through the Gbp4 inflammasome-dependent biosynthesis of prostaglandin D2. Our results point to GBPs as key inflammasome adaptors required for prostaglandin biosynthesis and bacterial clearance by neutrophils and suggest that transient activation of the inflammasome may be used to treat bacterial infections. PMID:27363812

  7. Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins

    PubMed Central

    Tyrkalska, Sylwia D.; Candel, Sergio; Angosto, Diego; Gómez-Abellán, Victoria; Martín-Sánchez, Fátima; García-Moreno, Diana; Zapata-Pérez, Rubén; Sánchez-Ferrer, Álvaro; Sepulcre, María P.; Pelegrín, Pablo; Mulero, Victoriano

    2016-01-01

    Inflammasomes are cytosolic molecular platforms that alert the immune system about the presence of infection. Here we report that zebrafish guanylate-binding protein 4 (Gbp4), an IFNγ-inducible GTPase protein harbouring a C-terminal CARD domain, is required for the inflammasome-dependent clearance of Salmonella Typhimurium (ST) by neutrophils in vivo. Despite the presence of the CARD domain, Gbp4 requires the universal inflammasome adaptor Asc for mediating its antibacterial function. In addition, the GTPase activity of Gbp4 is indispensable for inflammasome activation and ST clearance. Mechanistically, neutrophils are recruited to the infection site through the inflammasome-independent production of the chemokine (CXC motif) ligand 8 and leukotriene B4, and then mediate bacterial clearance through the Gbp4 inflammasome-dependent biosynthesis of prostaglandin D2. Our results point to GBPs as key inflammasome adaptors required for prostaglandin biosynthesis and bacterial clearance by neutrophils and suggest that transient activation of the inflammasome may be used to treat bacterial infections. PMID:27363812

  8. Acute Bacterial Cholangitis

    PubMed Central

    Zimmer, Vincent; Lammert, Frank

    2015-01-01

    Background Acute bacterial cholangitis for the most part owing to common bile duct stones is common in gastroenterology practice and represents a potentially life-threatening condition often characterized by fever, abdominal pain, and jaundice (Charcot's triad) as well as confusion and septic shock (Reynolds' pentad). Methods This review is based on a systematic literature review in PubMed with the search items ‘cholangitis’, ‘choledocholithiasis’, ‘gallstone disease’, ‘biliary infection’, and ‘biliary sepsis’. Results Although most patients respond to empiric broad-spectrum antibiotic treatment, timely endoscopic biliary drainage depending on the severity of the disease is required to eliminate the underlying obstruction. Specific recommendations have been derived from the Tokyo guideline working group consensus 2006 and its update in 2013, albeit poorly evidence-based, providing a comprehensive overview of diagnosis, classification, risk stratification, and treatment algorithms in acute bacterial cholangitis. Conclusion Prompt clinical recognition and accurate diagnostic workup including adequate laboratory assessment and (aetiology-oriented) imaging are critical steps in the management of cholangitis. Treatment is directed at the two major interrelated pathophysiologic components, i.e. bacterial infection (immediate antimicrobial therapy) and bile duct obstruction (biliary drainage). As for the latter, transpapillary endoscopic drainage by stent or nasobiliary drain and/or same-session bile duct clearance, depending on individual disease severity, represent first-line treatment approaches. PMID:26468310

  9. Bacterial Sialidase

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Data shows that elevated sialidase in bacterial vaginosis patients correlates to premature births in women. Bacterial sialidase also plays a significant role in the unusual colonization of Pseudomonas aeruginosa in cystic fibrosis patients. Crystals of Salmonella sialidase have been reproduced and are used for studying the inhibitor-enzyme complexes. These inhibitors may also be used to inhibit a trans-sialidase of Trypanosome cruzi, a very similar enzyme to bacterial sialidase, therefore preventing T. cruzi infection, the causitive agent of Chagas' disease. The Center for Macromolecular Crystallography suggests that inhibitors of bacterial sialidases can be used as prophylactic drugs to prevent bacterial infections in these critical cases.

  10. Diminishing Adult Egocentrism when Estimating What Others Know

    ERIC Educational Resources Information Center

    Thomas, Ruthann C.; Jacoby, Larry L.

    2013-01-01

    People often use what they know as a basis to estimate what others know. This egocentrism can bias their estimates of others' knowledge. In 2 experiments, we examined whether people can diminish egocentrism when predicting for others. Participants answered general knowledge questions and then estimated how many of their peers would know the…

  11. The Changing Black Teacher and Diminishing Opportunities for Black Teachers.

    ERIC Educational Resources Information Center

    Hilliard, Asa G., III

    Racism remains a distinct factor in problems faced by black teachers and teacher educators. The number of black teachers in the public schools is diminishing, especially in the southern states, where the black student population is the highest. The higher education environment has been undergoing drastic changes in faculty and student body…

  12. Innate Lymphocyte/Ly6C(hi) Monocyte Crosstalk Promotes Klebsiella Pneumoniae Clearance.

    PubMed

    Xiong, Huizhong; Keith, James W; Samilo, Dane W; Carter, Rebecca A; Leiner, Ingrid M; Pamer, Eric G

    2016-04-21

    Increasing antibiotic resistance among bacterial pathogens has rendered some infections untreatable with available antibiotics. Klebsiella pneumoniae, a bacterial pathogen that has acquired high-level antibiotic resistance, is a common cause of pulmonary infections. Optimal clearance of K. pneumoniae from the host lung requires TNF and IL-17A. Herein, we demonstrate that inflammatory monocytes are rapidly recruited to the lungs of K. pneumoniae-infected mice and produce TNF, which markedly increases the frequency of IL-17-producing innate lymphoid cells. While pulmonary clearance of K. pneumoniae is preserved in neutrophil-depleted mice, monocyte depletion or TNF deficiency impairs IL-17A-dependent resolution of pneumonia. Monocyte-mediated bacterial uptake and killing is enhanced by ILC production of IL-17A, indicating that innate lymphocytes engage in a positive-feedback loop with monocytes that promotes clearance of pneumonia. Innate immune defense against a highly antibiotic-resistant bacterial pathogen depends on crosstalk between inflammatory monocytes and innate lymphocytes that is mediated by TNF and IL-17A. PMID:27040495

  13. 30 CFR 56.11008 - Restricted clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Restricted clearance. 56.11008 Section 56.11008 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Travelways § 56.11008 Restricted clearance. Where...

  14. 49 CFR 192.325 - Underground clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Lines and Mains § 192.325 Underground clearance. (a) Each transmission line must be installed with at... the transmission line. If this clearance cannot be attained, the transmission line must be protected... the requirements of paragraph (a) or (b) of this section, each plastic transmission line or main...

  15. 49 CFR 192.325 - Underground clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Lines and Mains § 192.325 Underground clearance. (a) Each transmission line must be installed with at... the transmission line. If this clearance cannot be attained, the transmission line must be protected... the requirements of paragraph (a) or (b) of this section, each plastic transmission line or main...

  16. 49 CFR 192.325 - Underground clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Lines and Mains § 192.325 Underground clearance. (a) Each transmission line must be installed with at... the transmission line. If this clearance cannot be attained, the transmission line must be protected... the requirements of paragraph (a) or (b) of this section, each plastic transmission line or main...

  17. 24 CFR 35.1340 - Clearance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... abatement of lead-based paint or lead-based paint hazards shall be performed in accordance with 40 CFR 745... the steps set forth at 40 CFR 745.227(e)(8). If clearance is being performed after lead-based paint... certified to perform risk assessments or lead-based paint inspections. (b) Clearance following...

  18. 24 CFR 35.1340 - Clearance.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... abatement of lead-based paint or lead-based paint hazards shall be performed in accordance with 40 CFR 745... the steps set forth at 40 CFR 745.227(e)(8). If clearance is being performed after lead-based paint... certified to perform risk assessments or lead-based paint inspections. (b) Clearance following...

  19. 24 CFR 35.1340 - Clearance.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... abatement of lead-based paint or lead-based paint hazards shall be performed in accordance with 40 CFR 745... the steps set forth at 40 CFR 745.227(e)(8). If clearance is being performed after lead-based paint... certified to perform risk assessments or lead-based paint inspections. (b) Clearance following...

  20. 24 CFR 35.1340 - Clearance.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... abatement of lead-based paint or lead-based paint hazards shall be performed in accordance with 40 CFR 745... the steps set forth at 40 CFR 745.227(e)(8). If clearance is being performed after lead-based paint... certified to perform risk assessments or lead-based paint inspections. (b) Clearance following...

  1. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Clearance certificate. 122.77 Section 122.77 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart;...

  2. AHERA CLEARANCE AT TWENTY ABATEMENT SITES

    EPA Science Inventory

    A study was conducted during the summer of 1988 to document Asbestos Hazard Emergency Response Act (AHERA) clearance air sampling practices and clearance concentrations of airborne asbestos at 20 asbestos-abatement sites in New Jersey. ach abatement took place in a school buildin...

  3. AHERA CLEARANCE AT TWENTY ABATEMENT SITES

    EPA Science Inventory

    A study was conducted during the summer of 1988 to document Asbestos Hazard Emergency Response Act (AHERA) clearance air-sampling practices and clearance concentrations of airborne asbestos at 20 asbestos-abatement sites in New Jersey. Each abatement took place in a school buildi...

  4. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... nose wheel landing gear) or nine inches (for each airplane with tail wheel landing gear) between each propeller and the ground with the landing gear statically deflected and in the level takeoff, or taxiing... the corresponding landing gear strut bottomed. (b) Water clearance. There must be a clearance of...

  5. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... nose wheel landing gear) or nine inches (for each airplane with tail wheel landing gear) between each propeller and the ground with the landing gear statically deflected and in the level takeoff, or taxiing... the corresponding landing gear strut bottomed. (b) Water clearance. There must be a clearance of...

  6. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Departing From the United States § 122.77 Clearance certificate. (a) Aircraft departing from the U.S. One... director to show that clearance is granted. (b) Scheduled aircraft. If a scheduled aircraft clears at...

  7. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Departing From the United States § 122.77 Clearance certificate. (a) Aircraft departing from the U.S. One... director to show that clearance is granted. (b) Scheduled aircraft. If a scheduled aircraft clears at...

  8. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Departing From the United States § 122.77 Clearance certificate. (a) Aircraft departing from the U.S. One... director to show that clearance is granted. (b) Scheduled aircraft. If a scheduled aircraft clears at...

  9. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Departing From the United States § 122.77 Clearance certificate. (a) Aircraft departing from the U.S. One... director to show that clearance is granted. (b) Scheduled aircraft. If a scheduled aircraft clears at...

  10. Intelligent Engine Systems: HPT Clearance Control

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Advanced Thermally Actuated Clearance Control System underwent several studies. Improved flow path isolation quantified what can be gained by making the HPT case nearly adiabatic. The best method of heat transfer was established, and finally two different borrowed air cooling circuits were evaluated to be used for the HPT Active Clearance Control System.

  11. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... be processed for a security clearance in accordance with 32 CFR part 353 and the provisions of this... shall be accomplished in accordance with 32 CFR part 159. The investigative requirement shall be the... 32 National Defense 1 2014-07-01 2014-07-01 false Security clearance. 154.16 Section...

  12. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... be processed for a security clearance in accordance with 32 CFR part 353 and the provisions of this... shall be accomplished in accordance with 32 CFR part 159. The investigative requirement shall be the... 32 National Defense 1 2010-07-01 2010-07-01 false Security clearance. 154.16 Section...

  13. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... be processed for a security clearance in accordance with 32 CFR part 353 and the provisions of this... shall be accomplished in accordance with 32 CFR part 159. The investigative requirement shall be the... 32 National Defense 1 2012-07-01 2012-07-01 false Security clearance. 154.16 Section...

  14. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  15. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  16. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  17. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  18. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  19. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  20. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  1. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  2. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  3. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  4. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  5. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  6. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  7. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  8. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  9. Diminished Macrophage Apoptosis and Reactive Oxygen Species Generation after Phorbol Ester Stimulation in Crohn's Disease

    PubMed Central

    Palmer, Christine D.; Rahman, Farooq Z.; Sewell, Gavin W.; Ahmed, Afshan; Ashcroft, Margaret; Bloom, Stuart L.; Segal, Anthony W.; Smith, Andrew M.

    2009-01-01

    Background Crohn's Disease (CD) is a chronic relapsing disorder characterized by granulomatous inflammation of the gastrointestinal tract. Although its pathogenesis is complex, we have recently shown that CD patients have a systemic defect in macrophage function, which results in the defective clearance of bacteria from inflammatory sites. Methodology/Principal Findings Here we have identified a number of additional macrophage defects in CD following diacylglycerol (DAG) homolog phorbol-12-myristate-13-acetate (PMA) activation. We provide evidence for decreased DNA fragmentation, reduced mitochondrial membrane depolarization, impaired reactive oxygen species production, diminished cytochrome c release and increased IL-6 production compared to healthy subjects after PMA exposure. The observed macrophage defects in CD were stimulus-specific, as normal responses were observed following p53 activation and endoplasmic reticulum stress. Conclusion These findings add to a growing body of evidence highlighting disordered macrophage function in CD and, given their pivotal role in orchestrating inflammatory responses, defective apoptosis could potentially contribute to the pathogenesis of CD. PMID:19907654

  10. Bacterial Proteasomes

    PubMed Central

    Jastrab, Jordan B.; Darwin, K. Heran

    2015-01-01

    Interest in bacterial proteasomes was sparked by the discovery that proteasomal degradation is required for the pathogenesis of Mycobacterium tuberculosis, one of the world's deadliest pathogens. Although bacterial proteasomes are structurally similar to their eukaryotic and archaeal homologs, there are key differences in their mechanisms of assembly, activation, and substrate targeting for degradation. In this article, we compare and contrast bacterial proteasomes with their archaeal and eukaryotic counterparts, and we discuss recent advances in our understanding of how bacterial proteasomes function to influence microbial physiology. PMID:26488274

  11. Xenon spill distribution and room clearance.

    PubMed

    Kelsey, C A; Telepak, R J

    1999-11-01

    The purpose of these studies was to investigate actual xenon gas clearance times under different exhaust conditions, to compare them with the calculated clearance times, to observe the distribution of the xenon gas while it was being exhausted from the room, and to determine the cause of a stationary xenon cloud that appeared on some clinical images. Clearance times with and without a flexible exhaust hose placed next to a simulated 133Xe gas spill were compared with clearance times measured in a room with all exhaust closed off. Two gamma cameras were used to observe the transport and exhaust of xenon following a simulated spill. Clearance times with the flexible exhaust hose were less than one minute because the xenon gas was removed before it had a chance to disperse into the room. Conventional room clearance calculations based on uniform mixing and measured exhaust rates yielded a clearance time of 22 min. The source of an artifactual stationary cloud image was discovered to be a small amount of xenon trapped between the collimator and camera face. A negative pressure and dedicated exhaust can be even more effective in exhausting spilled xenon from a room than air transfer calculations predict. The authors believe the flexible hose should always be used. PMID:10524516

  12. Oxygen radicals diminish dopamine transporter function in rat striatum.

    PubMed

    Fleckenstein, A E; Metzger, R R; Beyeler, M L; Gibb, J W; Hanson, G R

    1997-09-01

    Incubation of striatal synaptosomes with the oxygen radical generating enzyme, xanthine oxidase, decreased [3H]dopamine uptake: an effect attributable to a decreased Vmax. Concurrent incubation with the superoxide radical scavenger, superoxide dismutase, abolished the xanthine oxidase-induced decrease. These results indicate that, like methamphetamine administration in vivo, reactive oxygen species diminish dopamine transporter function in vitro. The significance of these findings to mechanisms responsible for effects of methamphetamine is discussed. PMID:9346337

  13. Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia

    PubMed Central

    2014-01-01

    Background Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in view the significant role of metabolic alterations in cancer, we hypothesized that a ketogenic diet may diminish glycolytic flux in tumor cells to alleviate cachexia syndrome and, hence, may provide an efficient therapeutic strategy. Results We observed reduced glycolytic flux in tumor cells upon treatment with ketone bodies. Ketone bodies also diminished glutamine uptake, overall ATP content, and survival in multiple pancreatic cancer cell lines, while inducing apoptosis. A decrease in levels of c-Myc, a metabolic master regulator, and its recruitment on glycolytic gene promoters, was in part responsible for the metabolic phenotype in tumor cells. Ketone body-induced intracellular metabolomic reprogramming in pancreatic cancer cells also leads to a significantly diminished cachexia in cell line models. Our mouse orthotopic xenograft models further confirmed the effect of a ketogenic diet in diminishing tumor growth and cachexia. Conclusions Thus, our studies demonstrate that the cachectic phenotype is in part due to metabolic alterations in tumor cells, which can be reverted by a ketogenic diet, causing reduced tumor growth and inhibition of muscle and body weight loss. PMID:25228990

  14. Diminished Reality Based on Image Inpainting Considering Background Geometry.

    PubMed

    Kawai, Norihiko; Sato, Tomokazu; Yokoya, Naokazu

    2016-03-01

    Diminished reality aims to remove real objects from video images and fill in the missing regions with plausible background textures in real time. Most conventional methods based on image inpainting achieve diminished reality by assuming that the background around a target object is almost planar. This paper proposes a new diminished reality method that considers background geometries with less constraints than the conventional ones. In this study, we approximate the background geometry by combining local planes, and improve the quality of image inpainting by correcting the perspective distortion of texture and limiting the search area for finding similar textures as exemplars. The temporal coherence of texture is preserved using the geometries and camera pose estimated by visual-simultaneous localization and mapping (SLAM). The mask region that includes a target object is robustly set in each frame by projecting a 3D region, rather than tracking the object in 2D image space. The effectiveness of the proposed method is successfully demonstrated using several experimental environments. PMID:26829239

  15. Advanced optical blade tip clearance measurement system

    NASA Technical Reports Server (NTRS)

    Ford, M. J.; Honeycutt, R. E.; Nordlund, R. E.; Robinson, W. W.

    1978-01-01

    An advanced electro-optical system was developed to measure single blade tip clearances and average blade tip clearances between a rotor and its gas path seal in an operating gas turbine engine. This system is applicable to fan, compressor, and turbine blade tip clearance measurement requirements, and the system probe is particularly suitable for operation in the extreme turbine environment. A study of optical properties of blade tips was conducted to establish measurement system application limitations. A series of laboratory tests was conducted to determine the measurement system's operational performance characteristics and to demonstrate system capability under simulated operating gas turbine environmental conditions. Operational and environmental performance test data are presented.

  16. Nucleotide-mediated airway clearance.

    PubMed

    Schmid, Andreas; Clunes, Lucy A; Salathe, Mathias; Verdugo, Pedro; Dietl, Paul; Davis, C William; Tarran, Robert

    2011-01-01

    A thin layer of airway surface liquid (ASL) lines the entire surface of the lung and is the first point of contact between the lung and the environment. Surfactants contained within this layer are secreted in the alveolar region and are required to maintain a low surface tension and to prevent alveolar collapse. Mucins are secreted into the ASL throughout the respiratory tract and serve to intercept inhaled pathogens, allergens and toxins. Their removal by mucociliary clearance (MCC) is facilitated by cilia beating and hydration of the ASL by active ion transport. Throughout the lung, secretion, ion transport and cilia beating are under purinergic control. Pulmonary epithelia release ATP into the ASL which acts in an autocrine fashion on P2Y(2) (ATP) receptors. The enzymatic network describes in Chap. 2 then mounts a secondary wave of signaling by surface conversion of ATP into adenosine (ADO), which induces A(2B) (ADO) receptor-mediated responses. This chapter offers a comprehensive description of MCC and the extensive ramifications of the purinergic signaling network on pulmonary surfaces. PMID:21560046

  17. Plasma Creatinine Clearance in the Dog

    ERIC Educational Resources Information Center

    Frazier, Loy W.

    1977-01-01

    Lists materials and methods for an experiment that demonstrates the concept of glomerular filtration rate (GFR) using anesthesized dogs. In the dog, GFR is equivalent to the renal plasma clearance of exogenous creatinine. (CS)

  18. Shear joint capability versus bolt clearance

    NASA Technical Reports Server (NTRS)

    Lee, H. M.

    1992-01-01

    The results of a conservative analysis approach into the determination of shear joint strength capability for typical space-flight hardware as a function of the bolt-hole clearance specified in the design are presented. These joints are comprised of high-strength steel fasteners and abutments constructed of aluminum alloys familiar to the aerospace industry. A general analytical expression was first arrived at which relates bolt-hole clearance to the bolt shear load required to place all joint fasteners into a shear transferring position. Extension of this work allowed the analytical development of joint load capability as a function of the number of fasteners, shear strength of the bolt, bolt-hole clearance, and the desired factor of safety. Analysis results clearly indicate that a typical space-flight hardware joint can withstand significant loading when less than ideal bolt hole clearances are used in the design.

  19. Shear-Joint Capability Versus Bolt Clearance

    NASA Technical Reports Server (NTRS)

    Lee, H. M.

    1994-01-01

    NASA Technical Memorandum presents theoretical study of relationships between load-bearing capabilities of shear joints that comprise plates clamped together by multiple bolts and clearances between bolts and boltholes in those joints.

  20. Compressor airfoil tip clearance optimization system

    SciTech Connect

    Little, David A.; Pu, Zhengxiang

    2015-08-18

    A compressor airfoil tip clearance optimization system for reducing a gap between a tip of a compressor airfoil and a radially adjacent component of a turbine engine is disclosed. The turbine engine may include ID and OD flowpath boundaries configured to minimize compressor airfoil tip clearances during turbine engine operation in cooperation with one or more clearance reduction systems that are configured to move the rotor assembly axially to reduce tip clearance. The configurations of the ID and OD flowpath boundaries enhance the effectiveness of the axial movement of the rotor assembly, which includes movement of the ID flowpath boundary. During operation of the turbine engine, the rotor assembly may be moved axially to increase the efficiency of the turbine engine.

  1. Voltage-clearance recommendations for printed boards

    SciTech Connect

    Jennings, C W; Cave, G; Evans, A; Harrington, D J; Kirchenbaum, J; Martz, R E; Mierendorf, R C; Smith, G A

    1980-01-01

    Present and future trends in printed board designs point to higher circuit densities with narrower lines and closer spacings. Some designers are now laying out boards with 0.13 mm lines and spacings. The reduction of nominal spacing between conductive elements has raised questions concerning the adequacy of present voltage-clearance recommendations. The present recommendations are considered too conservative in that they are weighted with large safety factors, especially for small clearances, and are frequently disregarded by many designers. Published voltage breakdown measurements made on printed boards with comb patterns with their enhanced conductor test lengths show breakdowns occurring at much higher voltages than those specified for the clearances in existing documents. A Task Group was set up to review published breakdown measurements and to make any additional measurements necessary to provide voltage-clearance recommendations. These recommendations are reported.

  2. Year in review 2014: airway clearance.

    PubMed

    Strickland, Shawna L

    2015-04-01

    The respiratory therapist has had integrated adjuncts to improve mucus clearance for decades. However, there is a lack of literature describing the impact of these interventions on specific patient populations, resulting in an inability to make recommendations about the use of devices and techniques. The purpose of this article is to review recent literature regarding airway clearance therapies in a manner that is most likely to have interest to the readers of Respiratory Care. PMID:25784773

  3. Controls Considerations for Turbine Active Clearance Control

    NASA Technical Reports Server (NTRS)

    Melcher, Kevin J.

    2004-01-01

    This presentation discusses active control of turbine tip clearance from a control systems perspective. It is a subset of charts that were presented at the 2003 meeting of the International Society of Air Breathing Engines which was held August 31 through September 5 in Cleveland, Ohio. The associated reference paper is cited at the end of the presentation. The presentation describes active tip clearance control research being conducted by NASA to improve turbine engine systems. The target application for this effort is commercial aircraft engines. However, it is believed that the technologies developed as part of this research will benefit a broad spectrum of current and future turbomachinery. The first part of the presentation discusses the concept of tip clearance, problems associated with it, and the benefits of controlling it. It lays out a framework for implementing tip clearance controls that enables the implementation to progress from purely analytical to hardware-in-the-loop to fully experimental. And it briefly discusses how the technologies developed will be married to the previously described ACC Test Rig for hardware-in-the-loop demonstrations. The final portion of the presentation, describes one of the key technologies in some detail by presenting equations and results for a functional dynamic model of the tip clearance phenomena. As shown, the model exhibits many of the clearance dynamics found in commercial gas turbine engines. However, initial attempts to validate the model identified limitations that are being addressed to make the model more realistic.

  4. ADAPTIVE CLEARANCE CONTROL SYSTEMS FOR TURBINE ENGINES

    NASA Technical Reports Server (NTRS)

    Blackwell, Keith M.

    2004-01-01

    The Controls and Dynamics Technology Branch at NASA Glenn Research Center primarily deals in developing controls, dynamic models, and health management technologies for air and space propulsion systems. During the summer of 2004 I was granted the privilege of working alongside professionals who were developing an active clearance control system for commercial jet engines. Clearance, the gap between the turbine blade tip and the encompassing shroud, increases as a result of wear mechanisms and rubbing of the turbine blades on shroud. Increases in clearance cause larger specific fuel consumption (SFC) and loss of efficient air flow. This occurs because, as clearances increase, the engine must run hotter and bum more fuel to achieve the same thrust. In order to maintain efficiency, reduce fuel bum, and reduce exhaust gas temperature (EGT), the clearance must be accurately controlled to gap sizes no greater than a few hundredths of an inch. To address this problem, NASA Glenn researchers have developed a basic control system with actuators and sensors on each section of the shroud. Instead of having a large uniform metal casing, there would be sections of the shroud with individual sensors attached internally that would move slightly to reform and maintain clearance. The proposed method would ultimately save the airline industry millions of dollars.

  5. Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement

    PubMed Central

    Schiller, Daniela; Kanen, Jonathan W.; LeDoux, Joseph E.; Monfils, Marie-H.; Phelps, Elizabeth A.

    2013-01-01

    Controlling learned defensive responses through extinction does not alter the threat memory itself, but rather regulates its expression via inhibitory influence of the prefrontal cortex (PFC) over amygdala. Individual differences in amygdala–PFC circuitry function have been linked to trait anxiety and posttraumatic stress disorder. This finding suggests that exposure-based techniques may actually be least effective in those who suffer from anxiety disorders. A theoretical advantage of techniques influencing reconsolidation of threat memories is that the threat representation is altered, potentially diminishing reliance on this PFC circuitry, resulting in a more persistent reduction of defensive reactions. We hypothesized that timing extinction to coincide with threat memory reconsolidation would prevent the return of defensive reactions and diminish PFC involvement. Two conditioned stimuli (CS) were paired with shock and the third was not. A day later, one stimulus (reminded CS+) but not the other (nonreminded CS+) was presented 10 min before extinction to reactivate the threat memory, followed by extinction training for all CSs. The recovery of the threat memory was tested 24 h later. Extinction of the nonreminded CS+ (i.e., standard extinction) engaged the PFC, as previously shown, but extinction of the reminded CS+ (i.e., extinction during reconsolidation) did not. Moreover, only the nonreminded CS+ memory recovered on day 3. These results suggest that extinction during reconsolidation prevents the return of defensive reactions and diminishes PFC involvement. Reducing the necessity of the PFC–amygdala circuitry to control defensive reactions may help overcome a primary obstacle in the long-term efficacy of current treatments for anxiety disorders. PMID:24277809

  6. Diminished KCC2 confounds synapse specificity of LTP during senescence.

    PubMed

    Ferando, Isabella; Faas, Guido C; Mody, Istvan

    2016-09-01

    The synapse specificity of long-term potentiation (LTP) ensures that no interference arises from inputs irrelevant to the memory to be encoded. In hippocampi of aged (21-28 months) mice, LTP was relayed to unstimulated synapses, blemishing its synapse specificity. Diminished levels of the K(+)/Cl(-) cotransporter KCC2 and a depolarizing GABAA receptor-mediated synaptic component following LTP were the most likely causes for the spreading of potentiation, unveiling mechanisms hindering information storage in the aged brain and identifying KCC2 as a potential target for intervention. PMID:27500406

  7. 48 CFR 801.602-76 - Business clearance review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or...

  8. 48 CFR 801.602-76 - Business clearance review.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or...

  9. 48 CFR 801.602-76 - Business clearance review.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or...

  10. 19 CFR 4.61 - Requirements for clearance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Requirements for clearance. 4.61 Section 4.61 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES Foreign Clearances § 4.61 Requirements for clearance. (a) Application for clearance. A...

  11. 48 CFR 945.603-70 - Plant clearance function.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Plant clearance function... Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the contracting officer shall assume all responsibilities of the plant clearance...

  12. 48 CFR 945.603-70 - Plant clearance function.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Plant clearance function... Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the contracting officer shall assume all responsibilities of the plant clearance...

  13. 48 CFR 801.602-76 - Business clearance review.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or...

  14. Bacterial Keratitis

    MedlinePlus

    ... very quickly, and if left untreated, can cause blindness. The bacteria usually responsible for this type of ... to intense ultraviolet radiation exposure, e.g. snow blindness or welder's arc eye). Next Bacterial Keratitis Symptoms ...

  15. Diminished appetitive startle modulation following targeted inhibition of prefrontal cortex.

    PubMed

    Hurlemann, René; Arndt, Stephan; Schlaepfer, Thomas E; Reul, Juergen; Maier, Wolfgang; Scheele, Dirk

    2015-01-01

    From an evolutionary perspective the startle eye-blink response forms an integral part of the human avoidance behavioral repertoire and is typically diminished by pleasant emotional states. In major depressive disorder (MDD) appetitive motivation is impaired, evident in a reduced interference of positive emotion with the startle response. Given the pivotal role of frontostriatal neurocircuitry in orchestrating appetitive motivation, we hypothesized that inhibitory transcranial magnetic stimulation (TMS) would reduce appetitive neuromodulation in a manner similar to MDD. Based on a pre-TMS functional MRI (fMRI) experiment we selected the left dorsolateral and dorsomedial prefrontal cortices as target regions for subsequent sham-controlled inhibitory theta-burst TMS (TBS) in 40 healthy male volunteers. Consistent with our hypothesis, between-group comparisons revealed a TBS-induced inhibition of appetitive neuromodulation, manifest in a diminished startle response suppression by hedonic stimuli. Collectively, our results suggest that functional integrity of left dorsolateral and dorsomedial prefrontal cortex is critical for mediating a pleasure-induced down-regulation of avoidance responses which may protect the brain from a depressogenic preponderance of defensive stress. PMID:25752944

  16. Diminished appetitive startle modulation following targeted inhibition of prefrontal cortex

    PubMed Central

    Hurlemann, René; Arndt, Stephan; Schlaepfer, Thomas E.; Reul, Juergen; Maier, Wolfgang; Scheele, Dirk

    2015-01-01

    From an evolutionary perspective the startle eye-blink response forms an integral part of the human avoidance behavioral repertoire and is typically diminished by pleasant emotional states. In major depressive disorder (MDD) appetitive motivation is impaired, evident in a reduced interference of positive emotion with the startle response. Given the pivotal role of frontostriatal neurocircuitry in orchestrating appetitive motivation, we hypothesized that inhibitory transcranial magnetic stimulation (TMS) would reduce appetitive neuromodulation in a manner similar to MDD. Based on a pre-TMS functional MRI (fMRI) experiment we selected the left dorsolateral and dorsomedial prefrontal cortices as target regions for subsequent sham-controlled inhibitory theta-burst TMS (TBS) in 40 healthy male volunteers. Consistent with our hypothesis, between-group comparisons revealed a TBS-induced inhibition of appetitive neuromodulation, manifest in a diminished startle response suppression by hedonic stimuli. Collectively, our results suggest that functional integrity of left dorsolateral and dorsomedial prefrontal cortex is critical for mediating a pleasure-induced down-regulation of avoidance responses which may protect the brain from a depressogenic preponderance of defensive stress. PMID:25752944

  17. Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR)

    PubMed Central

    2011-01-01

    Background With infertility populations in the developed world rapidly aging, treatment of diminished ovarian reserve (DOR) assumes increasing clinical importance. Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances with DOR, and is now utilized by approximately one third of all IVF centers world-wide. Increasing DHEA utilization and publication of a first prospectively randomized trial now warrants a systematic review. Methods PubMed, Cochrane and Ovid Medline were searched between 1995 and 2010 under the following strategy: [ and diminished ovarian reserve or ovarian function >]. Bibliographies of relevant publications were further explored for additional relevant citations. Since only one randomized study has been published, publications, independent of evidence levels and quality assessment, were reviewed. Results Current best available evidence suggests that DHEA improves ovarian function, increases pregnancy chances and, by reducing aneuploidy, lowers miscarriage rates. DHEA over time also appears to objectively improve ovarian reserve. Recent animal data support androgens in promoting preantral follicle growth and reduction in follicle atresia. Discussion Improvement of oocyte/embryo quality with DHEA supplementation potentially suggests a new concept of ovarian aging, where ovarian environments, but not oocytes themselves, age. DHEA may, thus, represent a first agent beneficially affecting aging ovarian environments. Others can be expected to follow. PMID:21586137

  18. Targeting heparanase overcomes chemoresistance and diminishes relapse in myeloma.

    PubMed

    Ramani, Vishnu C; Zhan, Fenghuang; He, Jianbo; Barbieri, Paola; Noseda, Alessandro; Tricot, Guido; Sanderson, Ralph D

    2016-01-12

    In most myeloma patients, even after several rounds of intensive therapy, drug resistant tumor cells survive and proliferate aggressively leading to relapse. In the present study, gene expression profiling of tumor cells isolated from myeloma patients after sequential rounds of chemotherapy, revealed for the first time that heparanase, a potent promoter of myeloma growth and progression, was elevated in myeloma cells that survived therapy. Based on this clinical data, we hypothesized that heparanase was involved in myeloma resistance to drug therapy. In several survival and viability assays, elevated heparanase expression promoted resistance of myeloma tumor cells to chemotherapy. Mechanistically, this enhanced survival was due to heparanase-mediated ERK signaling. Importantly, use of the heparanase inhibitor Roneparstat in combination with chemotherapy clearly diminished the growth of disseminated myeloma tumors in vivo. Moreover, use of Roneparstat either during or after chemotherapy diminished regrowth of myeloma tumors in vivo following therapy. These results provide compelling evidence that heparanase is a promising, novel target for overcoming myeloma resistance to therapy and that targeting heparanase has the potential to prevent relapse in myeloma and possibly other cancers. PMID:26624982

  19. Lipopolysaccharide increases cell surface P-glycoprotein that exhibits diminished activity in intestinal epithelial cells.

    PubMed

    Mishra, Jayshree; Zhang, Qiuye; Rosson, Jessica L; Moran, John; Dopp, John M; Neudeck, Brien L

    2008-10-01

    Increasingly, it is recognized that commensal microflora regulate epithelial cell processes through the dynamic interaction of pathogen-associated molecular patterns and host pattern recognition receptors such as Toll-like receptor 4 (TLR4). We therefore investigated the effects of bacterial lipopolysaccharide (LPS) on intestinal P-glycoprotein (P-gp) expression and function. Human SW480 (P-gp+/TLR4+) and Caco-2 (P-gp+/TLR4-) cells were treated with medium control or LPS (100 ng/ml) for 24 h prior to study. P-gp function was assessed by measuring the intracellular concentration of rhodamine 123 (Rh123). To confirm P-gp-specific effects, breast cancer resistance protein (BCRP/ABCG2) and multidrug resistance-associated protein 2 (MRP-2/ABCC2) were also analyzed. Treatment of SW480 cells with LPS led to diminished P-gp activity, which could be prevented with polymyxin B (control: 207+/-16 versus LPS: 402+/-22 versus LPS+polymyxin B: 238+/-26 pmoles Rh123/mg protein, p<0.05 control versus LPS). These effects could be blocked by using polymyxin B and were not seen in the P-gp+/TLR4--Caco-2 cell line (control: 771+/-28 versus LPS: 775+/-59 pmoles Rh123/mg protein). Total cellular levels of P-gp did not change in LPS-treated SW480 cells; however, a significant increase in cell surface P-gp was detected. No change in activity, total protein, or apically located MRP-2 was detected following LPS treatment. Sequence analysis confirmed wild-type status of SW480 cells. These data suggest that activation of TLR4 in intestinal epithelial cells leads to an increase in plasma membrane P-gp that demonstrates a diminished capacity to transport substrate. PMID:18687802

  20. Diminished dose minimally invasive radioguided parathyroidectomy: a case for radioguidance.

    PubMed

    You, Christopher J; Zapas, John L

    2007-07-01

    Minimally invasive radioguided parathyroidectomy (MIRP) has been established as an alternative to bilateral neck exploration (BNE) for primary hyperparathyroidism. We investigate whether a diminished dose of technetium-99m sestamibi gives similar results to the standard dose. One hundred one patients were offered MIRP or diminished-dose MIRP (ddMIRP). Patients received intravenous Tc-99m sestamibi at a dose of either 25 mCi 1.5 hours or 5 mCi 1 hour preoperatively. The procedure was terminated when the 20 per cent rule was satisfied. All tissue was confirmed to be parathyroid tissue by frozen section analysis. In addition, intraoperative parathyroid hormone levels were measured in a majority of patients. Patients who failed IOM underwent BNE. Frozen section analysis and intraoperative parathyroid hormone monitoring were also performed in the BNEs. Postoperatively, serum calcium levels were measured at 1 week and 6 months. Fifteen per cent of patients were male and 85 per cent were female. The median age was 63 years (range, 25-89 years). The first 58 patients had the standard dose of 25 mCi, whereas 43 patients had ddMIRP. Six patients (10%) failed intraoperative mapping in the MIRP group and were found to have single-gland disease. Five patients (12%) failed intraoperative mapping in the ddMIRP group. However, two patients were identified to have multigland disease making the true failure rate of intraoperative mapping 7 per cent (three patients). Median operative times for MIRP, ddMIRP, and BNE were 40 minutes, 46 minutes, and 105 minutes, respectively. The 20 per cent rule was satisfied in 96 per cent of patients undergoing MIRP and 98 per cent of patients undergoing ddMIRP. Frozen section analysis and intraoperative parathyroid hormone monitoring did not result in a change in management. Median follow up was 193 days and serum calcium levels at 6 months were normal. Diminished-dose MIRP is a feasible alternative to standard-dose MIRP without compromising

  1. Clinical application of plasma clearance of iohexol on feline patients.

    PubMed

    Miyamoto, K

    2001-09-01

    Glomerular filtration rate (GFR) was estimated by plasma clearance of iohexol (PCio) in 52 conscious cats presented for a variety of reasons to Angel Animal Hospital over a 2-year period. Cats were divided into four groups according to their clinical conditions and reasons for measuring PCio. The median PCio (ml/min/kg) was 3.68 in normal cats (NM), 2.39 in cats with suspected renal disease (SP), 1.35 in cats referred to confirm renal dysfunction (RD), and 0.84 in cats with apparent clinical signs of renal failure (RF). There was a significant difference between the results for each group. The respective medians of blood urea nitrogen (BUN) and plasma creatinine concentration (Pcr) (mg/dl) were 15 and 1.40 in NM cats, 21 and 1.71 in SP cats, 30 and 2.20 in RD cats, and 48 and 3.30 in RF cats. The reference values of BUN and Pcr were 21 +/- 7 mg/dl and 1.5 +/- 0.4 mg/dl (mean +/- SD). Diminished renal function could not be detected in SP cats by either BUN or Pcr, while a marked decrease of GFR was demonstrated before BUN and Pcr increased, indicating the insensitivity of BUN and Pcr in detecting renal dysfunction in cats. PCio can be performed non-invasively in conscious cats, which improves the veterinarian's ability to detect early stages of chronic renal disease. PMID:11876631

  2. Assessment of Total Variation Diminishing schemes in combustion instability problems

    NASA Technical Reports Server (NTRS)

    Wang, Z. J.; Yang, H. Q.; Przekwas, A. J.

    1993-01-01

    Numerical simulations of acoustic waves in a shear layer and in an idealized combustion chamber using high resolution Total Variation Diminishing (TVD) schemes has been carried out to study the effects of inherent scheme dissipation and dispersion errors of this class of problems. The numerical results are compared against available exact solutions to quantify these errors. Several popular TVD limiters widely used in the Computational Fluid Dynamics (CFD) community have been assessed. Osher-Chakravarthy limiters are modified so that they can be used in explicit schemes. Among all the limiters investigated, Osher-Chakravarthy third-order limiter is identified as having performed the best. It is also found that all TVD schemes have exceptionally small dispersive errors.

  3. Social Presence Diminishes Contagious Yawning in the Laboratory

    PubMed Central

    Gallup, Andrew; Church, Allyson M.; Miller, Heather; Risko, Evan F.; Kingstone, Alan

    2016-01-01

    Contagious yawning may be a useful measure of social psychological functioning, and thus it is important to evaluate the variables influencing its expression in laboratory settings. Previous research has documented that humans yawn less frequently in crowded environments and when under direct observation, but the impact of social presence on contagious yawning remains unknown. Here we present the first study to systematically alter the degree of social presence experienced by participants in the laboratory to determine its effect on contagious yawning frequency. Our results demonstrate that both implied and actual social presence significantly diminish yawn contagion in comparison to a control condition, indicating a key social component to contagious yawning. These findings provide a framework for pursuing additional research investigating the social factors influencing contagious yawning, while also offering applications for measuring this response in laboratory settings. PMID:27112374

  4. Glycerol clearance in alcoholic liver disease.

    PubMed Central

    Johnston, D G; Alberti, K G; Wright, R; Blain, P G

    1982-01-01

    Glycerol clearance was studied by a primed dose-constant infusion technique in 14 patients with alcoholic liver disease and six normal control subjects. Fasting blood glycerol concentrations were raised in the alcoholic subjects (0.09 +/- 0.01 vs 0.06 +/- 0.01 mumol/l, p less than 0.05) and glycerol clearance was impaired (24.5 +/- 1.9 vs 37.5 +/- 3.2 ml/kg/min, p less than 0.005). Endogenous production rate of glycerol and distribution space at steady state were similar in alcoholic and control subjects. The metabolic clearance rate of glycerol correlated negatively with basal glycerol concentrations. Thus tissue uptake of glycerol is impaired in liver disease. As glycerol is metabolised primarily in the liver by conversion to glucose, these data suggest a defect of gluconeogenesis in alcoholic liver disease. PMID:7076002

  5. Necessary Clearance to Prevent Side Flashes

    NASA Astrophysics Data System (ADS)

    Shindo, Takatoshi; Asakawa, Akira; Honda, Hideki; Sakae, Maki; Tanaka, Shuusaku

    Side flashes often occur when lightning strikes a tree and cause injury or death of human beings staying nearby the tree. Necessary clearance to prevent the side flash has been said to be 2 m, but the physical meaning of the value is unclear. In this paper, we have proposed a model of side flashes based on the physics of discharges and necessary clearance has been calculated. Furthermore, we have carried out model experiments of the side flash using real trees of a heights of 3.5 m and a naturally growing tree of a height of more than 10 m. The results of the model experiments have verified the proposed theory and it is concluded that clearance of more than 3 m from a tree is necessary to prevent side flashes from the tree.

  6. Pharmacologic agents for mucus clearance in bronchiectasis.

    PubMed

    Nair, Girish B; Ilowite, Jonathan S

    2012-06-01

    There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis. PMID:22640851

  7. Prediction of hepatic microsomal intrinsic clearance and human clearance values for drugs.

    PubMed

    Nikolic, Katarina; Agababa, Danica

    2009-10-01

    Twenty-nine drugs of different structures were used in theoretical QSAR analysis of human hepatic microsomal intrinsic clearance (in vitro T(1/2) and in vitro CL'(int)) and whole body clearance (CL(blood)). The examined compounds demonstrated a wide range of scaled intrinsic clearance values. Constitutional, geometrical, physico-chemical and electronic descriptors were computed for the examined structures by use of the Marvin Sketch 5.1.3_2, the Chem3D Ultra 7.0.0 and the Dragon 5.4 program. Partial least squares regression (PLSR), has been applied for selection of the most relevant molecular descriptors and development of quantitative structure-activity relationship (QSAR) model for human hepatic microsomal intrinsic clearance (in vitro T(1/2)). Optimal QSAR models with nine and ten variables, R(2)>0.808 and cross-validation parameter q(pre)(2)>0.623, were selected and compared. Since the microsomal in vitro T(1/2) data can be used for calculation of in vitro CL'(int) and in vivo CL(blood), the developed QSAR model will enable one to analyze the kinetics of cytochrome P450-mediated reactions in term of intrinsic clearance and whole body clearance. A comparison is made between predictions produced from the QSAR analysis and experimental data, and there appears to be generally satisfactory correlations with the literature values for intrinsic clearance data. PMID:19713138

  8. Enhanced Clearance of Pseudomonas aeruginosa by Peroxisome Proliferator-Activated Receptor Gamma.

    PubMed

    Bedi, Brahmchetna; Yuan, Zhihong; Joo, Myungsoo; Zughaier, Susu M; Goldberg, Joanna B; Arbiser, Jack L; Hart, C Michael; Sadikot, Ruxana T

    2016-07-01

    The pathogenic profile of Pseudomonas aeruginosa is related to its ability to secrete a variety of virulence factors. Quorum sensing (QS) is a mechanism wherein small diffusible molecules, specifically acyl-homoserine lactones, are produced by P. aeruginosa to promote virulence. We show here that macrophage clearance of P. aeruginosa (PAO1) is enhanced by activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ). Macrophages treated with a PPARγ agonist (pioglitazone) showed enhanced phagocytosis and bacterial killing of PAO1. It is known that PAO1 QS molecules are inactivated by PON-2. QS molecules are also known to inhibit activation of PPARγ by competitively binding PPARγ receptors. In accord with this observation, we found that infection of macrophages with PAO1 inhibited expression of PPARγ and PON-2. Mechanistically, we show that PPARγ induces macrophage paraoxonase 2 (PON-2), an enzyme that degrades QS molecules produced by P. aeruginosa Gene silencing studies confirmed that enhanced clearance of PAO1 in macrophages by PPARγ is PON-2 dependent. Further, we show that PPARγ agonists also enhance clearance of P. aeruginosa from lungs of mice infected with PAO1. Together, these data demonstrate that P. aeruginosa impairs the ability of host cells to mount an immune response by inhibiting PPARγ through secretion of QS molecules. These studies define a novel mechanism by which PPARγ contributes to the host immunoprotective effects during bacterial infection and suggest a role for PPARγ immunotherapy for P. aeruginosa infections. PMID:27091928

  9. Bacterial Immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A variety of bacterial agents reside in and around the environment that can cause illness and death in a poultry flock. Many cause disseminated disease while others exert more local effects such as the respiratory or gastrointestinal tract. The host, for our current purposes the laying hen, has de...

  10. 30 CFR 57.11008 - Restricted clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Restricted clearance. 57.11008 Section 57.11008 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Travelways and Escapeways Travelways-Surface and Underground §...

  11. 30 CFR 57.11010 - Stairstep clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Stairstep clearance. 57.11010 Section 57.11010 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Travelways and Escapeways Travelways-Surface and Underground...

  12. 15 CFR 752.15 - Export clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... accordance with requirements of the Foreign Trade Statistics Regulations (15 CFR part 30) and § 758.1 of the... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Export clearance. 752.15 Section 752... OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS...

  13. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... be processed for a security clearance in accordance with 32 CFR part 353 and the provisions of this... shall be accomplished in accordance with 32 CFR part 159. The investigative requirement shall be the... security personnel who have no access to classified information. (11) To drivers, chauffeurs and...

  14. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... be processed for a security clearance in accordance with 32 CFR part 353 and the provisions of this... shall be accomplished in accordance with 32 CFR part 159. The investigative requirement shall be the... security personnel who have no access to classified information. (11) To drivers, chauffeurs and...

  15. Mediators and mucociliary clearance in asthma.

    PubMed

    Pavia, D; Lopez-Vidriero, M T; Clarke, S W

    1987-01-01

    Lung mucociliary clearance is significantly reduced in asthmatic patients compared to healthy controls even during clinical remission. Further retardation in mucous clearance occurs during sleep per se and this may be a contributing factor to nocturnal asthma. Chemical mediators of anaphylaxis appear to have various and, sometimes opposing effects on the two essential components for mucociliary clearance, namely cilia and mucus. Some mediators such as leukotrienes C4 and D4 are potent secretagogues and histamine increases the water flux into the lumen of the airways from the mucosa. Slow-reacting substance of anaphylaxis (SRS-A) reduces mucus transport whereas histamine enhances it. Ciliostimulation has been reported following allergen challenge and this contrasts with the cilioinhibitory effect of asthmatics' sputa. It appears however, that the net effect of the various chemicals of anaphylaxis is one of impairment of mucus clearance. Some pharmacological agents, used for the relief of bronchospasm and control of asthma, also stimulate mucociliary transport, a desirable additional effect. PMID:3311245

  16. 28 CFR 524.74 - Activities clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Activities clearance. 524.74 Section 524.74 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INMATE ADMISSION, CLASSIFICATION, AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74...

  17. 49 CFR 192.325 - Underground clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Underground clearance. 192.325 Section 192.325 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM...

  18. Overeducation and depressive symptoms: diminishing mental health returns to education.

    PubMed

    Bracke, Piet; Pattyn, Elise; von dem Knesebeck, Olaf

    2013-11-01

    In general, well-educated people enjoy better mental health than those with less education. As a result, some wonder whether there are limits to the mental health benefits of education. Inspired by the literature on the expansion of tertiary education, this article explores marginal mental health returns to education and studies the mental health status of overeducated people. To enhance the validity of the findings we use two indicators of educational attainment - years of education and ISCED97 categories - and two objective indicators of overeducation (the realised matches method and the job analyst method) in a sample of the working population of 25 European countries (unweighted sample N = 19,089). Depression is measured using an eight-item version of the CES-D scale. We find diminishing mental health returns to education. In addition, overeducated people report more depression symptoms. Both findings hold irrespective of the indicators used. The results must be interpreted in the light of the enduring expansion of education, as our findings show that the discussion of the relevance of the human capital perspective, and the diploma disease view on the relationship between education and modern society, is not obsolete. PMID:23909439

  19. Overexpression of Catalase Diminishes Oxidative Cysteine Modifications of Cardiac Proteins

    PubMed Central

    Yao, Chunxiang; Behring, Jessica B.; Shao, Di; Sverdlov, Aaron L.; Whelan, Stephen A.; Elezaby, Aly; Yin, Xiaoyan; Siwik, Deborah A.; Seta, Francesca; Costello, Catherine E.; Cohen, Richard A.; Matsui, Reiko; Colucci, Wilson S.; McComb, Mark E.; Bachschmid, Markus M.

    2015-01-01

    Reactive protein cysteine thiolates are instrumental in redox regulation. Oxidants, such as hydrogen peroxide (H2O2), react with thiolates to form oxidative post-translational modifications, enabling physiological redox signaling. Cardiac disease and aging are associated with oxidative stress which can impair redox signaling by altering essential cysteine thiolates. We previously found that cardiac-specific overexpression of catalase (Cat), an enzyme that detoxifies excess H2O2, protected from oxidative stress and delayed cardiac aging in mice. Using redox proteomics and systems biology, we sought to identify the cysteines that could play a key role in cardiac disease and aging. With a ‘Tandem Mass Tag’ (TMT) labeling strategy and mass spectrometry, we investigated differential reversible cysteine oxidation in the cardiac proteome of wild type and Cat transgenic (Tg) mice. Reversible cysteine oxidation was measured as thiol occupancy, the ratio of total available versus reversibly oxidized cysteine thiols. Catalase overexpression globally decreased thiol occupancy by ≥1.3 fold in 82 proteins, including numerous mitochondrial and contractile proteins. Systems biology analysis assigned the majority of proteins with differentially modified thiols in Cat Tg mice to pathways of aging and cardiac disease, including cellular stress response, proteostasis, and apoptosis. In addition, Cat Tg mice exhibited diminished protein glutathione adducts and decreased H2O2 production from mitochondrial complex I and II, suggesting improved function of cardiac mitochondria. In conclusion, our data suggest that catalase may alleviate cardiac disease and aging by moderating global protein cysteine thiol oxidation. PMID:26642319

  20. Mechanisms of viral clearance and persistence.

    PubMed

    Borrow, P

    1997-01-01

    Using examples predominantly drawn from study of the lymphocytic choriomeningitis virus (LCMV) model system, this review describes the mechanisms involved in control of virus infections by the cell-mediated immune response, and some of the different strategies viruses have evolved to evade such immune clearance so that they can persist in their hosts. The important role played by the CD8+ cytotoxic lymphocyte (CTL) response in clearance of many systemic virus infections is discussed; and it is emphasized that although CD8+ CTL are classically thought of as lymphocytes which mediate lysis of virus-infected target cells, the principal mechanism by which CD8+ T cells effect clearance of persistent and many acute virus infections via production of antiviral cytokines such as tumour necrosis factor-alpha and interferon-gamma, not via destruction of virus-producing cells. To avoid immune-mediated clearance, viruses frequently use a combination of several different strategies. These can be grouped into mechanisms for avoiding recognition by the immune response (such as establishing latent infections, replicating in immune-privileged sites, down-regulating the expression of immune recognition signals on the surface of infected cells, or undergoing antigenic variation); and mechanisms for suppressing the immune response. The latter include generalized immune suppression mechanisms, and strategies for more precisely disabling the specific immune response such as inducing tolerance or exhaustion of virus-specific CTL. The value of understanding both immune clearance mechanisms and viral evasion strategies in the rational design of immune-based therapies to combat persistent virus infections is discussed. PMID:9429206

  1. 75 FR 70341 - Agency Information Collection Activities: Emergency Clearance Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-17

    ... From the Federal Register Online via the Government Publishing Office SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Emergency Clearance Request The Social Security..._Submission@omb.eop.gov . (SSA), Social Security Administration, DCBFM, Attn: Reports Clearance Officer,...

  2. 19 CFR 122.26 - Entry and clearance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AIR COMMERCE REGULATIONS Private Aircraft § 122.26 Entry and clearance. Private aircraft, as defined... information as set forth in § 122.22(c), and grants electronic clearance via electronic mail or telephone....

  3. 14 CFR 375.24 - Entry and clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... REGULATIONS NAVIGATION OF FOREIGN CIVIL AIRCRAFT WITHIN THE UNITED STATES Rules Generally Applicable § 375.24 Entry and clearance. All U.S. entry and clearance requirements for aircraft, passengers, crews,...

  4. 14 CFR 375.24 - Entry and clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REGULATIONS NAVIGATION OF FOREIGN CIVIL AIRCRAFT WITHIN THE UNITED STATES Rules Generally Applicable § 375.24 Entry and clearance. All U.S. entry and clearance requirements for aircraft, passengers, crews,...

  5. 14 CFR 375.24 - Entry and clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... REGULATIONS NAVIGATION OF FOREIGN CIVIL AIRCRAFT WITHIN THE UNITED STATES Rules Generally Applicable § 375.24 Entry and clearance. All U.S. entry and clearance requirements for aircraft, passengers, crews,...

  6. 14 CFR 375.24 - Entry and clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REGULATIONS NAVIGATION OF FOREIGN CIVIL AIRCRAFT WITHIN THE UNITED STATES Rules Generally Applicable § 375.24 Entry and clearance. All U.S. entry and clearance requirements for aircraft, passengers, crews,...

  7. 10 CFR 95.17 - Processing facility clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.17 Processing facility clearance. (a... pertinent laws, and the nature of international security and information exchange agreements. The...

  8. 77 FR 44641 - Critical Infrastructure Private Sector Clearance Program Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-30

    ... SECURITY Critical Infrastructure Private Sector Clearance Program Request AGENCY: National Protection and... Programs Directorate (NPPD), Office of Infrastructure Protection (IP) will submit the following Information... Infrastructure Private Sector Clearance Program (PSCP). DHS previously published this ICR in the Federal...

  9. 77 FR 21989 - Critical Infrastructure Private Sector Clearance Program Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ... SECURITY Critical Infrastructure Private Sector Clearance Program Request AGENCY: National Protection and... Programs Directorate (NPPD), Office of Infrastructure Protection (IP) will submit the following Information... information provided. SUPPLEMENTARY INFORMATION: The Critical Infrastructure Private Sector Clearance...

  10. WWW-based data entry for document clearance requests

    SciTech Connect

    Stasiak, D.M.

    1997-10-08

    All documents created at Argonne must be cleared before being published. The clearance process is coordinated by the Publications and Record Services. The Electronic Document Review and Clearance System (EDRC) consists of a Web-based system for submission of clearance requests, an electronic staging area for document awaiting review, and Web-based review and clearance of documents. This report covers the document clearing process, the EDRC system, expected benefits/costs, and a demonstration.

  11. Inflammation and clearance of Chlamydia trachomatis in enteric and nonenteric mucosae.

    PubMed

    Igietseme, J U; Portis, J L; Perry, L L

    2001-03-01

    Immunization(s) fostering the induction of genital mucosa-targeted immune effectors is the goal of vaccines against sexually transmitted diseases. However, it is uncertain whether vaccine administration should be based on the current assumptions about the common mucosal immune system. We investigated the relationship between mucosal sites of infection, infection-induced inflammation, and immune-mediated bacterial clearance in mice using the epitheliotropic pathogen Chlamydia trachomatis. Chlamydial infection of the conjunctival, pulmonary, or genital mucosae stimulated significant changes in tissue architecture with dramatic up-regulation of the vascular addressin, VCAM, a vigorous mixed-cell inflammatory response with an influx of alpha4beta1+ T cells, and clearance of bacteria within 30 days. Conversely, intestinal mucosa infection was physiologically inapparent, with no change in expression of the local MAdCAM addressin, no VCAM induction, no histologically detectable inflammation, and no tissue pathology. Microbial clearance was complete within 60 days in the small intestine but bacterial titers remained at high levels for at least 8 months in the large intestine. These findings are compatible with the notion that VCAM plays a functional role in recruiting cells to inflammatory foci, and its absence from the intestinal mucosa contributes to immunologic homeostasis at that site. Also, expression of type 1 T cell-mediated immunity to intracellular Chlamydia may exhibit tissue-specific variation, with the rate and possibly the mechanism(s) of clearance differing between enteric and nonenteric mucosae. The implications of these data for the common mucosal immune system and the delivery of vaccines against mucosal pathogens are discussed. PMID:11179361

  12. Citrobacter rodentium mouse model of bacterial infection.

    PubMed

    Crepin, Valerie F; Collins, James W; Habibzay, Maryam; Frankel, Gad

    2016-10-01

    Infection of mice with Citrobacter rodentium is a robust model to study bacterial pathogenesis, mucosal immunology, the health benefits of probiotics and the role of the microbiota during infection. C. rodentium was first isolated by Barthold from an outbreak of mouse diarrhea in Yale University in 1972 and was 'rediscovered' by Falkow and Schauer in 1993. Since then the use of the model has proliferated, and it is now the gold standard for studying virulence of the closely related human pathogens enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively). Here we provide a detailed protocol for various applications of the model, including bacterial growth, site-directed mutagenesis, mouse inoculation (from cultured cells and after cohabitation), monitoring of bacterial colonization, tissue extraction and analysis, immune responses, probiotic treatment and microbiota analysis. The main protocol, from mouse infection to clearance and analysis of tissues and host responses, takes ∼5 weeks to complete. PMID:27606775

  13. Neonatal Pulmonary Macrophage Depletion Coupled to Defective Mucus Clearance Increases Susceptibility to Pneumonia and Alters Pulmonary Immune Responses.

    PubMed

    Saini, Yogesh; Wilkinson, Kristen J; Terrell, Kristy A; Burns, Kimberlie A; Livraghi-Butrico, Alessandra; Doerschuk, Claire M; O'Neal, Wanda K; Boucher, Richard C

    2016-02-01

    Resident immune cells (e.g., macrophages [MΦs]) and airway mucus clearance both contribute to a healthy lung environment. To investigate interactions between pulmonary MΦ function and defective mucus clearance, a genetic model of lysozyme M (LysM) promoter-mediated MΦ depletion was generated, characterized, and crossed with the sodium channel β subunit transgenic (Scnn1b-Tg) mouse model of defective mucus clearance. Diphtheria toxin A-mediated depletion of LysM(+) pulmonary MΦs in wild-type mice with normal mucus clearance resulted in lethal pneumonia in 24% of neonates. The pneumonias were dominated by Pasteurella pneumotropica and accompanied by emaciation, neutrophilic inflammation, and elevated Th1 cytokines. The incidence of emaciation and pneumonia reached 51% when LysM(+) MΦ depletion was superimposed on the airway mucus clearance defect of Scnn1b-Tg mice. In LysM(+) MΦ-depleted Scnn1b-Tg mice, pneumonias were associated with a broader spectrum of bacterial species and a significant reduction in airway mucus plugging. Bacterial burden (CFUs) was comparable between Scnn1b-Tg and nonpneumonic LysM(+) MΦ-depleted Scnn1b-Tg mice. However, the nonpneumonic LysM(+) MΦ-depleted Scnn1b-Tg mice exhibited increased airway inflammation, the presence of neutrophilic infiltration, and increased levels of inflammatory cytokines in bronchoalveolar lavage fluid compared with Scnn1b-Tg mice. Collectively, these data identify key MΦ-mucus clearance interactions with respect to both infectious and inflammatory components of muco-obstructive lung disease. PMID:26121027

  14. 10 CFR 95.17 - Processing facility clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... clearances (PCLs); and (4) Appointing a U.S. citizen employee as the facility security officer. (b) An... NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.17 Processing facility clearance....

  15. Wear analysis of revolute joints with clearance in multibody systems

    NASA Astrophysics Data System (ADS)

    Bai, ZhengFeng; Zhao, Yang; Wang, XingGui

    2013-08-01

    In this work, the prediction of wear for revolute joint with clearance in multibody systems is investigated using a computational methodology. The contact model in clearance joint is established using a new hybrid nonlinear contact force model and the friction effect is considered by using a modified Coulomb friction model. The dynamics model of multibody system with clearance is established using dynamic segmentation modeling method and the computational process for wear analysis of clearance joint in multibody systems is presented. The main computational process for wear analysis of clearance joint includes two steps, which are dynamics analysis and wear analysis. The dynamics simulation of multibody system with revolute clearance joint is carried out and the contact forces are drawn and used to calculate the wear amount of revolute clearance joint based on the Archard's wear model. Finally, a four-bar multibody mechanical system with revolute clearance joint is used as numerical example application to perform the simulation and show the dynamics responses and wear characteristics of multibody systems with revolute clearance joint. The main results of this work indicate that the contact between the joint elements is wider and more frequent in some specific regions and the wear phenomenon is not regular around the joint surface, which causes the clearance size increase non-regularly after clearance joint wear. This work presents an effective method to predict wear of revolute joint with clearance in multibody systems.

  16. 10 CFR 95.17 - Processing facility clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Processing facility clearance. 95.17 Section 95.17 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.17 Processing facility clearance. (a) Following the receipt of an acceptable...

  17. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case....

  18. 48 CFR 945.670-1 - Plant clearance function.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... contracting officer shall assume all responsibilities of the plant clearance officer identified in 48 CFR 45... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Plant clearance function... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 945.670-1 Plant clearance function....

  19. 48 CFR 945.670-1 - Plant clearance function.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... contracting officer shall assume all responsibilities of the plant clearance officer identified in 48 CFR 45... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Plant clearance function... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 945.670-1 Plant clearance function....

  20. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case....

  1. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case....

  2. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case....

  3. 33 CFR 157.455 - Minimum under-keel clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Minimum under-keel clearance. 157... § 157.455 Minimum under-keel clearance. (a) The owner or operator of a tankship, that is not fitted with... written under-keel clearance guidance that includes— (1) Factors to consider when calculating the...

  4. 33 CFR 157.455 - Minimum under-keel clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Minimum under-keel clearance. 157... § 157.455 Minimum under-keel clearance. (a) The owner or operator of a tankship, that is not fitted with... written under-keel clearance guidance that includes— (1) Factors to consider when calculating the...

  5. 30 CFR 56.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance on adjacent tracks. 56.9103 Section..., Hauling, and Dumping Traffic Safety § 56.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  6. 30 CFR 57.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Clearance on adjacent tracks. 57.9103 Section..., Hauling, and Dumping Traffic Safety § 57.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  7. 30 CFR 56.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Clearance on adjacent tracks. 56.9103 Section..., Hauling, and Dumping Traffic Safety § 56.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  8. 30 CFR 57.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance on adjacent tracks. 57.9103 Section..., Hauling, and Dumping Traffic Safety § 57.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  9. 23 CFR Appendix B to Part 1327 - OMB Clearance

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false OMB Clearance B Appendix B to Part 1327 Highways NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURES FOR PARTICIPATING..., App. B Appendix B to Part 1327—OMB Clearance The OMB clearance number of this regulation is OMB...

  10. 61 FR 11709 - Real Estate Title Clearance and Loan Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    1996-03-22

    ... 0575-AB52 Real Estate Title Clearance and Loan Closing AGENCIES: Rural Housing Service, Rural Business... ``agency,'' amend the Real Estate Title Clearance and Loan Closing regulation. This action makes loan.... The proposed rule discussed the need to make real estate title clearance and loan closing...

  11. 59 FR- Real Estate Title Clearance and Loan Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    1994-05-11

    .... SUMMARY: The Farmers Home Administration (FmHA) proposes to amend its Real Estate Title Clearance and Loan... changes affect FmHA processing, real estate title clearance, and loan closing. Paperwork Reduction Act The... EO. Discussion FmHA recognizes the need to make Real Estate Title Clearance and Loan...

  12. 14 CFR 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas...

  13. 14 CFR 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas...

  14. 14 CFR 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas...

  15. 14 CFR § 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Customs clearance and visas. § 1260.63 Section § 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance...

  16. 14 CFR 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas...

  17. Evaluation of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M.; Lattime, Scott B.; Taylor, Shawn; DeCastro, Jonathan A.; Oswald, Jay; Melcher, Kevin J.

    2005-01-01

    Reducing blade tip clearances through active tip clearance control in the high pressure turbine can lead to significant reductions in emissions and specific fuel consumption as well as dramatic improvements in operating efficiency and increased service life. Current engines employ scheduled cooling of the outer case flanges to reduce high pressure turbine tip clearances during cruise conditions. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, reburst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). In an effort to improve upon current thermal methods, a first generation mechanically-actuated active clearance control (ACC) system has been designed and fabricated. The system utilizes independent actuators, a segmented shroud structure, and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. Ambient temperature performance tests of this first generation ACC system assessed individual seal component leakage rates and both static and dynamic overall system leakage rates. The ability of the nine electric stepper motors to control the position of the seal carriers in both open- and closed-loop control modes for single and multiple cycles was investigated. The ability of the system to follow simulated engine clearance transients in closed-loop mode showed the system was able to track clearances to within a tight tolerance ( 0.001 in. error).

  18. Evaluation of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M.; Lattime, Scott B.; DeCastro, Jonathan A.; Oswald, Jay; Melcher, Kevin J.

    2005-01-01

    Reducing blade tip clearances through active tip clearance control in the high pressure turbine can lead to significant reductions in emissions and specific fuel consumption as well as dramatic improvements in operating efficiency and increased service life. Current engines employ scheduled cooling of the outer case flanges to reduce high pressure turbine tip clearances during cruise conditions. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, reburst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). In an effort to improve upon current thermal methods, a first generation mechanically-actuated active clearance control (ACC) system has been designed and fabricated. The system utilizes independent actuators, a segmented shroud structure, and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. Ambient temperature performance tests of this first generation ACC system assessed individual seal component leakage rates and both static and dynamic overall system leakage rates. The ability of the nine electric stepper motors to control the position of the seal carriers in both open- and closed-loop control modes for single and multiple cycles was investigated. The ability of the system to follow simulated engine clearance transients in closed-loop mode showed the system was able to track clearances to within a tight tolerance (0.001 in. error).

  19. 30 CFR 56.9330 - Clearance for surface equipment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Clearance for surface equipment. 56.9330... NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Loading... Dumping Sites § 56.9330 Clearance for surface equipment. Continuous clearance of at least 30 inches...

  20. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main...

  1. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main...

  2. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  3. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  4. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  5. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  6. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  7. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 5 2014-04-01 2014-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main...

  8. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 5 2013-04-01 2013-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main...

  9. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 5 2012-04-01 2012-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main...

  10. 10 CFR 95.23 - Termination of facility clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.23 Termination of facility clearance. (a... determination that continued facility clearance is not in the interest of national security. (b) When...